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Surface-Enhanced Raman Spectroscopy for Biomedical Applications: Recent Advances and Future ChallengesClick to copy article linkArticle link copied!
- Linley Li LinLinley Li LinSixth People’s Hospital, School of Medicine & School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, P. R. ChinaMore by Linley Li Lin
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- Jing WangJing WangKey Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, Fujian Provincial Key Laboratory of Photonics Technology, Fujian Normal University, Fuzhou 350117, ChinaMore by Jing Wang
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- Chunchun LiChunchun LiSchool of Materials Science and Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, P. R. ChinaMore by Chunchun Li
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- Jian-An HuangJian-An HuangResearch Unit of Health Sciences and Technology, Faculty of Medicine, University of Oulu, Aapistie 5 A, 90220 Oulu, FinlandResearch Unit of Disease Networks, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Aapistie 5 A, 90220 Oulu, FinlandBiocenter Oulu, University of Oulu, Aapistie 5 A, 90220 Oulu, FinlandMore by Jian-An Huang
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- Ming LiMing LiSchool of Materials Science and Engineering, Central South University, Changsha, Hunan 410083, ChinaMore by Ming Li
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- Lam Bang Thanh NguyenLam Bang Thanh NguyenSchool of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 21 Nanyang Link, Singapore 637371More by Lam Bang Thanh Nguyen
- Xinyuan BiXinyuan BiSixth People’s Hospital, School of Medicine & School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, P. R. ChinaMore by Xinyuan Bi
- Dana Cialla-MayDana Cialla-MayLeibniz Institute of Photonic Technology, Member of Leibniz Health Technologies, Member of the Leibniz Centre for Photonics in Infection Research (LPI), Albert-Einstein-Straße 9, 07745 Jena, GermanyInstitute of Physical Chemistry (IPC) and Abbe Center of Photonics (ACP), Friedrich Schiller University Jena, Member of the Leibniz Centre for Photonics in Infection Research (LPI), Helmholtzweg 4, 07743 Jena, GermanyMore by Dana Cialla-May
- Pavel MatousekPavel MatousekCentral Laser Facility, Research Complex at Harwell, STFC Rutherford Appleton Laboratory, UKRI, Harwell Campus, Oxfordshire OX11 0QX, United KingdomDepartment of Physics and Astronomy, University of Exeter, Exeter EX4 4QL, United KingdomMore by Pavel Matousek
- Nicholas StoneNicholas StoneDepartment of Physics and Astronomy, University of Exeter, Exeter EX4 4QL, United KingdomMore by Nicholas Stone
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- Wei SongWei SongState Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun 130012, PR ChinaMore by Wei Song
- Zhou ChenZhou ChenSixth People’s Hospital, School of Medicine & School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, P. R. ChinaMore by Zhou Chen
- In Yee PhangIn Yee PhangKey Laboratory of Synthetic and Biological Colloids, Ministry of Education, International Joint Research Laboratory for Nano Energy Composites, School of Chemical and Material Engineering, Jiangnan University, Wuxi 214122, P. R. ChinaMore by In Yee Phang
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- Haoran ChenHaoran ChenSixth People’s Hospital, School of Medicine & School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, P. R. ChinaMore by Haoran Chen
- Zongyu WuZongyu WuSixth People’s Hospital, School of Medicine & School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, P. R. ChinaMore by Zongyu Wu
- Heng GuoHeng GuoDepartment of Biomedical Engineering, and Center for Remote Health Technologies and Systems Texas A&M University, College Station, Texas 77843, United StatesMore by Heng Guo
- Hao MaHao MaState Key Laboratory of Physical Chemistry of Solid Surfaces, Collaborative Innovation Center of Chemistry for Energy Materials (iChEM), Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM), Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, ChinaMore by Hao Ma
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- Siheng LuoSiheng LuoState Key Laboratory of Physical Chemistry of Solid Surfaces, Collaborative Innovation Center of Chemistry for Energy Materials (iChEM), Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM), Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, ChinaMore by Siheng Luo
- Sara MoscaSara MoscaCentral Laser Facility, Research Complex at Harwell, STFC Rutherford Appleton Laboratory, UKRI, Harwell Campus, Oxfordshire OX11 0QX, United KingdomMore by Sara Mosca
- Benjamin GardnerBenjamin GardnerDepartment of Physics and Astronomy, University of Exeter, Exeter EX4 4QL, United KingdomMore by Benjamin Gardner
- Yi-Tao LongYi-Tao LongMolecular Sensing and Imaging Center, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, P. R. ChinaMore by Yi-Tao Long
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- Bin RenBin RenState Key Laboratory of Physical Chemistry of Solid Surfaces, Collaborative Innovation Center of Chemistry for Energy Materials (iChEM), Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM), Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, ChinaMore by Bin Ren
- Shuming NieShuming NieDepartment of Bioengineering, University of Illinois at Urbana−Champaign, 1406 W. Green Street, Urbana, Illinois 61801, United StatesMore by Shuming Nie
- Bing ZhaoBing ZhaoState Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun 130012, PR ChinaMore by Bing Zhao
- Xing Yi Ling*Xing Yi Ling*Email: [email protected]School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 21 Nanyang Link, Singapore 637371Key Laboratory of Synthetic and Biological Colloids, Ministry of Education, International Joint Research Laboratory for Nano Energy Composites, School of Chemical and Material Engineering, Jiangnan University, Wuxi 214122, P. R. ChinaMore by Xing Yi Ling
- Jian Ye*Jian Ye*Email: [email protected]Sixth People’s Hospital, School of Medicine & School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, P. R. ChinaMore by Jian Ye
Abstract
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The year 2024 marks the 50th anniversary of the discovery of surface-enhanced Raman spectroscopy (SERS). Over recent years, SERS has experienced rapid development and became a critical tool in biomedicine with its unparalleled sensitivity and molecular specificity. This review summarizes the advancements and challenges in SERS substrates, nanotags, instrumentation, and spectral analysis for biomedical applications. We highlight the key developments in colloidal and solid SERS substrates, with an emphasis on surface chemistry, hotspot design, and 3D hydrogel plasmonic architectures. Additionally, we introduce recent innovations in SERS nanotags, including those with interior gaps, orthogonal Raman reporters, and near-infrared-II-responsive properties, along with biomimetic coatings. Emerging technologies such as optical tweezers, plasmonic nanopores, and wearable sensors have expanded SERS capabilities for single-cell and single-molecule analysis. Advances in spectral analysis, including signal digitalization, denoising, and deep learning algorithms, have improved the quantification of complex biological data. Finally, this review discusses SERS biomedical applications in nucleic acid detection, protein characterization, metabolite analysis, single-cell monitoring, and in vivo deep Raman spectroscopy, emphasizing its potential for liquid biopsy, metabolic phenotyping, and extracellular vesicle diagnostics. The review concludes with a perspective on clinical translation of SERS, addressing commercialization potentials and the challenges in deep tissue in vivo sensing and imaging.
This publication is licensed for personal use by The American Chemical Society.
Copyright © 2025 American Chemical Society
1. Introduction: At the Interface of SERS and Biomedicine
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Surface-enhanced Raman scattering or spectroscopy (SERS) has emerged as a transformative analytical technique at the intersection of nanotechnology and biomedical sciences. By leveraging the plasmonic properties of metallic nanostructured, SERS offers remarkable sensitivity, enabling the detection of molecular fingerprints even at the single-molecule level. Its discovery has not only given rise to an entirely new field of research in chemistry and biology but also opened a wide range of applications as an ultrasensitive analytical tool, including disease diagnostics, biomarker detection, cellular imaging, and therapeutic monitoring.
The year 1974 marked the inception of SERS technique based on silver (Ag) substrates. (1) Soon after, in the 1980s, the SERS technique began to be used in vitro for the detection of various biomolecules. (2−5) The research at that time primarily focused on the improvement of the SERS sensitivity and the interpretation of spectra. (6,7) By the late 1990s, the emergence of single-molecule SERS (8,9) pushed this technique once again to the forefront of biosensing applications. In 2008, Nie et al. achieved for the first time the in vivo tumor detection using gold (Au) SERS nanotags, opening up new exploration opportunities of SERS in live animals. (10) The past decade has seen a surge of interest in the application of SERS in biomedicine, driven by advancements in nanomaterial synthesis, substrate engineering, and spectral analysis techniques, especially artificial intelligence (AI). These developments have gradually expanded the potential application range of SERS from fundamental research to real-world clinical applications. Key areas of progress include the design of colloidal and solid-state SERS substrates for high-efficiency signal enhancement, the creation of SERS nanotags for multiplexed detection, and the integration of SERS platforms into wearable and microfluidic devices. Additionally, breakthroughs in spectral analysis, quantification methods, and machine learning techniques have opened new avenues for SERS-based diagnostics, enabling precise and reliable detection of nucleic acids, proteins, metabolites, and extracellular vesicles.
This review revisits the recent advances in SERS for biomedical applications over the past decade, exploring cutting-edge developments in substrate design, sensing platforms, and data analysis. We will discuss how innovations in SERS substrates─both colloidal and solid surface-based─have pushed the boundaries of sensitivity and specificity. We will also examine the growing role of SERS nanotags in biomedical sensing, alongside novel devices and chips that facilitate point-of-care diagnostics. Furthermore, this review addresses critical challenges in SERS quantification, including emerging techniques like digital SERS. The latest advancements in AI-assisted spectral analysis, from frequency analysis, noise reduction to spectral unmixing, have improved signal interpretation with the adoption of AI. Next, we will delve into the expanding applications of SERS in biomedicine, covering nucleic acid, protein, metabolite biosensing, as well as tissue bioimaging, and the use of SERS for in vivo deep sensing. Finally, this review provides a comprehensive overview of the current state of the field, while also outlining future challenges and opportunities for further advancements.
2. SERS Substrates: Colloidal Substrates
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Colloidal Au/Ag nanoparticles (NPs) are among the most widely used SERS substrates due to their ease of synthesis, reproducibility, and ability to provide strong plasmonic enhancement. However, a major challenge in utilizing agglomerated colloidal Au/Ag NPs for SERS analysis is ensuring that target molecules specifically adsorb at hotspot regions, where signal enhancement is most effective. The adsorption of target analytes onto plasmonic substrates can occur through direct or indirect mechanisms (Figure 1), which can be controlled by modifying the surface chemistry of the NPs, as detailed in Section 2.1. Such surface modifications can also facilitate the formation of self-assembled layers or agglomerated colloidal NPs, as discussed in Section 2.2. While ensuring adsorption at plasmonic hotspots remains a critical hurdle, we discuss various strategies to achieve adsorption at these critical regions in greater detail in Sections 2.3 and 2.4.
Figure 1
Figure 1. Schematic illustration of the direct and indirect adsorption.
2.1. Surface Chemistry and Solution-Phase Nanoparticles
One of the simplest and most effective methods to achieve strong plasmonic enhancement using colloids involves the use of inorganic salts to induce NP agglomeration. Briefly, plasmonic colloidal NPs are often stabilized by electrostatic forces provided by their capping ligands. The addition of high-concentration of inorganic salts disrupts the electric double layer and significantly weakens interparticle electrostatic repulsion, allowing the NPs to agglomerate via attractive van der Waals forces. As shown in Figure 1, the adsorption of target analytes within the plasmonic enhancement region can be categorized into two forms: direct and indirect adsorption. (11)
The capability for direct adsorption of analytes largely hinges on the surface chemistry of colloidal NPs. Typically, colloidal NPs are coated with a layer of ligands, which are used to direct the growth of the particles into structures and to prevent NP agglomeration. However, this also means that, for NPs capped with strongly adsorbed stabilizing agents, these prepared NPs can only be used to detect molecules with even higher affinity to them. For example, the two most employed stabilizers for directly controlling the morphology and dimensions of NPs are cetyltrimethylammonium bromide (CTAB) and cetyltrimethylammonium chloride (CTAC), which remain adsorbing strongly to NP surface. As a result, the as-prepared colloidal NPs are mostly limited to SERS studies of strongly adsorbing molecules, such as thiols and amines. For instance, Das et al. have demonstrated the trace-amount SERS analysis of Rhodamine 6G dye by using CTAB-capped NPs as the enhancing substrate. (12) Liz-Marzán et al. reported the detection of methylthioadenosine, which contains thiol and amine groups and is crucial to metabolic interactions between cancer cells and their microenvironment, using CTAC-capped NPs. (13)
To widen the range of target analytes, it is also possible to use pretreatment methods to remove and replace strongly adsorbing capping ligands prior to SERS analysis. For example, Tan et al. replaced CTAB by poly(4-styrenesulfonic acid) (PSS) and then citrate ions on Au nanorods surface, enabling the subsequent detection of several dyes and thiabendazole. (14) Zhang et al. showed that the H– generated in sodium borohydride solutions could replace thiols from the surface of Au NPs. (15) Since H– is not stable in solution and quickly undergoes reactions to H2, this leaves the surface of the NPs accessible for the adsorption of analyte molecules.
Alternatively, weakly adsorbing ligands, such as citrate, chloride ions, which can be easily replaced, can also serve as stabilizing agents for colloidal NPs. Typical examples of such colloids include citrate, hydroxylamine and sodium borohydride reduced Ag or Au colloids. As shown in Figure 2a, Bi et al. showed that Ag colloidal NPs stabilized with chloride ions can serve as a general substrate for the detection of a wide variety of analyte molecules down to single-molecule levels, including weakly adsorbing analytes such as glucose. (16) One challenge with using weakly adsorbing ligands for NP synthesis is controlling morphology, which is essential for achieving strong plasmonic enhancement. Bell and Xu et al. used Ag+ as a growth-directing agent to synthesize hollow Au nanostars. (17) The Ag+ is reduced to Ag0, becoming part of the particles and leaving the surface accessible for analyte adsorption. Moreover, the authors compared SERS activity of nanostars capped with chloride ions and polyvinyl propylene (PVP), finding that PVP capping significantly decreased SERS signals (Figure 2b).
Figure 2
Figure 2. Examples of solution-phase NP-based application. (a) Digital SERS analysis of paraquat in lake water and thiram in bean sprouts extract by using chloride-capped Ag NPs as the enhancing substrates. Reproduced from ref (16). Copyright 2024, The Authors, under exclusive license to Springer Nature Limited. (b) SERS spectra of CV, doxorubicin (DOX), niraparib (NI) obtained on pristine (i), hedroxyethyl-cellulose stabilized (ii), and PVP-capped Au nanostars. Reproduced from ref (17). Copyright 2021, The Authors. (c) SERS spectra of negatively charged dye labeled DNA using Ag NPs modified by spermine (blue), spermidine (red), and ethylenedioxy-diethylamine (black) as the enhancing substrates, respectively. Reproduced from ref (18). Copyright 2012, Royal Society of Chemistry. (d) SERS spectra of MDMA detected by Ag NPs modified with different feedstock proportion of mixed thiols, as well as the normal Raman spectrum of MDMA pow der. Reproduced from ref (19). Copyright 2012, Royal Society of Chemistry. (e) SERS analysis of methanol by using CB modified Au NPs as the enhancing substrates. Reproduced from ref (20). Copyright 2017, Royal Society of Chemistry.
Analyte molecules can also adsorb directly onto unoccupied nanoparticle surface sites. Bell and Xu et al. showed that the adsorption strength of citrate/chloride ion on Ag/Au surfaces is inversely proportional to surface coverage due to charge accumulation, limiting ion coverage and leaving accessible sites for polyaromatic hydrocarbons adsorption, enabling their SERS detection. (21) In contrast, this effect was absent when thiol molecules passivated the surface. (22)
In many cases, colloidal NPs are treated with solutions of inorganic salts (often referred to as the “agglomerating agent”), which induce NP agglomeration, and in turn, creates plasmonic hot-spots that generates strong field enhancement. Therefore, apart from the type of capping ligands, the agglomerating agent can also affect the surface chemistry of the colloidal NPs and their SERS performance. More specifically, the relative affinity between the agglomerating agent and analyte molecule for the enhancing surface is crucial, since the agglomerating agent could compete with the analyte molecule for enhancing surface, which in extreme cases, could completely hinder the adsorption of the analyte. For example, Bell et al. demonstrated that when using MgCl2 to induce agglomeration of Ag colloid, 2′-deoxyadenosine 5′-monophosphate (dAMP) did not show any SERS signal even at 1000 ppm level, as dAMP was out competed by chloride ions which adsorbed more strongly to the surface of Ag NPs. (23) In contrast, when MgSO4 was used, clear SERS signals of dAMP could be observed even at 3 ppb. In other cases, the agglomerating agent has been shown to be able to aid the adsorption of analytes. For example, Liu et al. showed that using halide salts as the agglomerating agent promoted the adsorption of polyaromatic hydrocarbons to colloidal Ag NPs. (24,25)
The indirect analyte adsorption requires the modification of NPs surfaces with a functional layer, which interacts and attracts target analytes to the surface of the enhancing material. In most cases, this approach is used to promote the adsorption of analyte molecules which otherwise interact weakly with the enhancing metal, (26−28) but have also been shown to be effective for inducing selectivity in the analysis of complex samples. (29−31) The most common type of modifier is the self-assembled monolayers (SAMs) of small molecules containing strongly adsorbing head groups and functional tail groups. For example, Graham et al. reported that SAMs of positively charged spermine can be used to functionalize Ag NPs to attract and detect negatively charged dye-labeled DNA (Figure 2c). (18) Similarly, by modifying the colloidal Ag NP surface with positively charged thiol, Bell et al. achieved the SERS analysis of nonadsorbing negatively charged analytes such as perchlorate and picric acid (an explosive) at micromolar level. (32) In some cases, SAMs consisted of a mixture of different types of small-molecules are used to increase the affinity of analytes onto the enhancing surface. For example, Bell et al. realized highly sensitivity SERS detection of 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”) by modifying the surface of Ag NPs with a mixed SAM consisted of sodium mercaptopropanesulfonate (MPS) and benzyl mercaptan (BZM), which attract the target analyte through the synergistic function of electrostatic attraction and hydrophobic interaction (Figure 2d). (19)
Another class of modifiers used to attract target analytes are large or macro molecules that possess specific structure that are capable of interacting with target analytes. For example, molecules with intercavities can be used as the “host”, to capture “guest” molecules through specific host–guest interactions. Baumberg and Scherman et al. reported the use of cucurbit[n]uril (CB[n]) adsorbed on the surface of Au NPs as a molecular cage to detect alcohol molecules via hydrogen bonding between the CB host and alcohol guest molecule (Figure 2e). (20) Besides host molecules, biological macromolecules such as antibodies and aptamers are also widely used as modifiers in SERS detection of bioanalytes. For example, Yu et al. reported a point-of-care SERS detection platform where SARS-CoV-2 antigen was specifically captured by aptamers functionalized on Au NPs, which enabled its SERS detection within 5 min. (33) Another type of macromolecules that has been widely studied as the modifiers for SERS is molecularly imprinted polymers due to their excellent selectivity and recognition capabilities. For example, Nguyen et al. reported a SERS substrate of Au nanorods coated with a molecularly imprinted polymer, which has been designed to selectively capture rhodamine B in a mixture of different dyes spiked in orange juice. (34)
An emerging class of functional modifiers are inorganic materials which are coated as shells on the surface of colloidal Au/Ag NPs to capture target molecules. The most commonly used shell material for this purpose are metal organic frameworks (MOFs). For example, Yang et al. reported Au nanorod@ZIF-8 NPs, which enabled selective detection of 4-nitrobenzenethiol at nanomolar concentration levels in the presence of whole blood. (35) In addition, 2D materials, such as graphene layers, have also been explored as shell materials for promoting analyte adsorption in SERS. (36)
In summary the surface chemistry of the colloidal NPs affects the performance of SERS substrates, since SERS is a short-range effect that makes the adsorption of the target analyte to the surface of the substrate material crucial in colloidal SERS. Within this context, a major challenge often faced by SERS users is the dilemma between having strong plasmonic enhancement and accessible surface properties, since the synthesis of colloidal NPs which provide strong plasmonic field enhancement typically require the use of strongly adsorbing growth directing agents. (37,38) Therefore, it will be important to develop novel methods which balances the plasmonic and surface properties of colloidal NPs, (39) since both properties play a significant role in successful SERS analysis. Finally, we should note that while the examples discussed in this section focused on colloidal NPs, the same underlining principles regarding analyte adsorption are applicable to advanced SERS substrates that are built from colloidal NPs.
2.2. Self-Assembled Nanoparticle at Water/Oil Interface
In addition to the external stimulation (e.g., by magnetic field) (40) and top-down construction (e.g., by e-beam lithography), (41) a particularly elegant method to form plasmonic NP aggregates for SERS enhancement is to assemble colloidal NPs at the water/oil (w/o) interface to form interfacial arrays. (42) Interfacial arrays of noble metal NPs were first reported in 1988 by Yogev et al., (43) while their first use as enhancing substrates in SERS was reported a year later by Gordon et al. (44) At the time, the authors showed the capabilities of interfacial Ag arrays by demonstrating resonant SERS (surface-enhanced resonant Raman spectroscopy, SERRS) detection of several different types of metal complexes. Since then, interfacial arrays of Ag and Au NPs have grown to become an important and popular class of enhancing substrates for SERS analysis.
It is now well-established that the assembly of solid colloidal NPs at the water–oil interface is driven by the reduction of interfacial energy between the immiscible liquid phases. (45) However, the surface of plasmonic colloidal NPs often carries charged ligand molecules which give the NPs a surface charge. This surface charge helps to maintain colloidal stability by providing interparticle electrostatic repulsion, but also prevents the charged NPs from packing tightly at the interface to form plasmonic hotspots. This makes the development of methods to overcome interparticle electrostatic repulsion crucial for the construction of SERS enhancing substrates via interfacial self-assembly. (46)
As shown in Figure 3a, the most straightforward way to overcome this issue is to remove the charged ligands by modifying the surface of the charged colloidal NPs with charge-neutral organic “modifiers”. For noble metals, modifiers are typically thiols and pyridines, with the most popular being poly(ethylene glycol)methyl ether thiol (PEG-SH) and polyvinylpyrrolidone. (47,48) A crucial disadvantage of the use of modifiers in SERS is that the strongly adsorbed modifiers passivate the surface of the enhancing material, which limits the type of molecules that can be detected using SERS. (49) As a result, SERS studies performed using interfacial nanoparticle assemblies formed via modifiers have been limited to the analysis of a small set of analyte molecules which either interacts strongly with the noble metal surface or with the modifier. (50,51) Another viable way to overcome interparticle electrostatic repulsion is to reduce the surface potential of the NPs. This could be achieved through the addition of a organic cosolvent, such as acetone or ethanol, into the aqueous phase of the biphasic system (Figure 3b). (52,53) In this case, the addition of cosolvents in the aqueous colloid lowers the ability of the aqueous phase to solvate ionic compounds and causes the charged ionic species on the surface of NPs to recombine with their ionic counterparts in solution. (54) This removes the electric double layer, which significantly weakens interparticle electrostatic repulsion. (55) Unlike the modifier approach, the cosolvent approach does not lead to the surface of the plasmonic NPs being passivated by strongly adsorbing modifiers. This advantage along with the simplicity of the method has made the cosolvent approach a widely used method for constructing interfacial arrays for SERS analysis. (56−58)
Figure 3
Figure 3. Methods and application of self-assembled NPs. (a–d) Schematic illustrations of the different methods for overcoming interparticle electrostatic repulsion in interfacial NP self-assembly. Panels a–d were adapted with permission from ref (46). Copyright 2021, The Royal Society of Chemistry. (e) Schematic illustrations of interfacial plasmonic arrays used as the enhancing substrate for SERS detection of norepinephrine in rat brain microdialysates. Reproduced with permission from ref (67). Copyright 2022, Wiley-VCH-GmbH. (f) Schematic illustration of in situ biphasic SERS performed using interfacial arrays as the enhancing substrate. (g) SERS spectra of (i) Au interfacial arrays, (ii–iii) Au interfacial arrays containing 10–3 and 10–5 M naphthalene introduced from the oil phase, (iv–vii) Au interfacial array containing 10–5 M naphthalene introduced from water, hexane, or chloroform phase of the interfacial array, respectively. Panels f–g were adapted with permission fromref (21). Copyright 2022, The Authors. (h) Examples of plasmonic interfacial arrays deposited on various supporting materials. The scalebars corresponds to 0.5 cm. Adapted with permissions from ref (68). Copyright 2021, The Authors. (I) Schematic illustration and photograph showing bacterial headspace probed in situ via SERS using interfacial arrays deposited on quartz as the enhancing substrate. Headspace SERS spectra of the time dependent adsorption from broth spiked with 10–2 M dimethyl disulfide. Adapted with permissions from ref (69). Copyright 2028, Wiley-VCH-GmbH.
Besides using cosolvents, an equally effective approach to induce interfacial self-assembly without passivating the NPs’ surface is to add hydrophilic salts, such as NaCl into the aqueous colloids. (51,59) As shown in Figure 3c, the Debye length of the electric double layer surrounding charged colloidal NPs shrinks with increasing ionic concentration. Therefore, the addition of salt acts similarly to the addition of a cosolvent and leads to a significant decrease to the electrostatic potential around the colloidal NPs. (60,61)
The main disadvantage of using cosolvents or salts to induce interfacial self-assembly is that the significant reduction to the surface potential of the colloidal NPs could also lead to uncontrolled aggregation that occurs in parallel to the self-assembly process. This inevitably leads to the formation of structural defects and/or large aggregates in the product interfacial NP-assemblies, (62,63) which significantly affects the reproducibility of the SERS measurements. To combat this issue, Lin et al., showed that a similar affect can also be achieved through the addition of a second type of oil to create a dual-interface system. (63) In this case, the oil phases need to have different densities and surface tension gradients relative to water, so that the NPs initially assembled at the interface with lower surface tension gradient will be transferred to and compressed at the interface with higher surface tension by Marangoni force.
More recently, Magdalena et al. reported a new class of chemical compounds, termed “promoters”, which could be used to induce self-assembly of various charged colloidal NPs, including Ag and Au NPs, into densely packed interfacial arrays for SERS analysis. (64) In general, promoters are amphiphilic salts, such as tetrabutylammonium nitrate, which carry an opposite charge to the colloidal NPs. As shown in Figure 3d, the amphiphilic property of the promoters allows them to reside at the interface to screen electrostatic repulsion between the adjacent NPs to enable the formation of densely packed nanoparticle arrays with strong plasmonic properties. (65) Importantly, although promoters were ionic salts they do not induce self-assembly via charge reduction like the common hydrophilic salts mentioned above, since the typical amount of promoter needed to induce self-assembly is at ∼ micromolar concentrations. This is far beneath the ionic concentrations required to significantly reduce the aggregation energy barrier, which overcomes the issue with unwanted aggregation in cosolvent or salt-induced self-assembly. In addition, the promoters do not adsorb directly to the surface of the metal NPs. This leaves the surface of the NPs accessible, which opens the possibility for SERS analysis of even weakly adsorbing analyte molecules. (66)
In general, plasmonic interfacial NP arrays are versatile enhancing substrates in SERS and have been used for the analysis of a wide range of analytes. For example, in an early demonstration by Cecchini et al., Au interfacial arrays were used as an enhancing substrate to detect both airborne and solubilized analyte molecules which included malachite green isothiocyanate, mercapto-5-nitrobenzimidazole, 4-methoxy-α-toluenethiol,2,4-dinitrotoluene, aniline, cysteine, and adenosine-5′-trophosphate with limits of detection reaching nanomolar levels. (59) More recently, Shi et al. utilized Au interfacial arrays functionalized with 4-(thiophen-3-ylethynyl)-benzaldehyde to achieve detection of norepinephrine, a neurotransmitter, in biofluid samples extracted from rat brain via microdialysis. (67) As shown in Figure 3e, the 4-(thiophen-3-ylethynyl)-benzaldehyde molecules exhibited dual-functionals, acting both as the modifier to induce interfacial self-assembly and as the Raman reporter for selective indirect detection of norepinephrine. This system allowed quantitative detection of norepinephrine down to 0.6 nM to be achieved within 4 min, which exceeded conventional methods including liquid chromatography–mass spectroscopy and fluorescence spectroscopy.
An advantage that comes uniquely with the use of interfacial arrays as SERS enhancing substrates is their biphasic nature that gives the NPs access to analytes distributed in both organic and aqueous solvents. Indeed, the pioneering work by Gordon et al. were performed in an effort to observe the SERS signals of organic metal complexes which were only soluble in oil. (43) In addition, the oil phase can also be used to extract and concentrate analyte molecules from samples to allow direct SERS analysis of complex real-life samples. For example, Ma et al. utilized the cyclohexane phase of interfacial arrays as an extracting agent which allowed multiplex detection of drug molecules in urine samples. (70)
More recently, interfacial arrays have also found applications as SERS substrates in fundamental research on surface chemistry and plasmonics. For example, Li et al. have taken advantage of the biphasic properties of interfacial arrays to study the effect of solvation and hydrophobic forces on the adsorption of polyaromatic hydrocarbons to Au NPs in situ via SERS (Figure 3f–g). (21) More specifically, this was performed by introducing the polyaromatic hydrocarbons into either the aqueous or oil phase of an interfacial array, which allowed the adsorption kinetics, relative affinity, and stability of the polyaromatic hydrocarbon–metal complex to be studied in situ using SERS. In another work, Zhang et al. took advantage of the contractable properties of interfacial arrays to study the effect of particle–particle gap distance on interparticle plasmonic coupling. (71) The interparticle spacing in Au interfacial arrays was dynamically controlled by regulating the size of the interface via solvent evaporation. Using thiophenol as a Raman tag, the authors observed a rise in the SERS signal intensity of thiophenol as the NPs were pushed closer together during the initial stages of solvent evaporation, which was attributed to the formation of plasmonic hotspots. Interestingly, as the NPs continued to move closer with further solvent evaporation, the SERS signals decreased rapidly and eventually dropped by nearly 3 orders of magnitude. This was attributed to the possibility of quantum effects that start to occur at subnanometer gap distances which would significantly influence the electromagnetic field enhancement.
Interfacial arrays can also be conveniently deposited onto various types of supporting materials to form free-standing SERS enhancing substrates which combine the functionalities of the plasmonic NPs and the solid support (Figure 3h). (68) For example, Kelly et al. showed that Ag and Au interfacial arrays deposited onto quartz support can be used as an enhancing substrate for direct SERS discrimination of live and dead bacteria. (72) As shown in Figure 3i, this method involved in situ SERS analysis of the headspace of bacterial cultures, which typically contained a fermentative metabolite, dimethyl disulfide, that adsorbed spontaneously to the plasmonic NPs to generate strong SERS signals. The sensitivity limit of the method was found to be 1.5 × 107 CFU/mL. This corresponded to detection of bacterial growth within 15 min, which was significantly faster than traditional approaches. In addition, the authors showed that the method was effective for seven different types of bacteria and could be completed using a portable Raman spectrometer, which makes this a potentially viable method for rapid bedside detection of bacterial infections.
Table 1 provides a more comprehensive summary of: the types of plasmonic NPs that have been used for interfacial self-assembly; the types of solid materials that have been used as supports for converting interfacial arrays into solid SERS enhancing substrates; and the types of analyte molecules that have been studied. Despite the excellent progress shown above, there are still challenges that remain in the use of interfacial arrays in SERS. For example, direct characterization of interfacial arrays remain highly challenging, which makes it crucial to develop novel characterization techniques and/or protocols that allow surface chemistry and particle packing to be probed in situ. (73,74) This will pave the way for the development of novel methods to rationally design and control the assembly behavior of NPs at a single-particle level to fine-tune the plasmonic property and SERS activity of interfacial arrays.
Table 1. Examples of Different Types of NPs That Have Been Used in Construction of Interfacial Arrays, Different Types of Support Material That Have Been Used to Convert Interfacial Arrays into Solid Composite Materials, And Different Types of Analyte Molecules That Have Been Studied Using Interfacial Arrays with SERS
| Particle | Support | Analyte |
|---|---|---|
| Ag nanowire (53) | Superhydrophobic needle (75) | Parathion (pesticide) (76) |
| Au nanorod (77) | Filter paper (78) | MicroRNA (biomolecule) (79) |
| Au@Ag nanocube (80) | Silicon wafer (81) | Trinitrotoluene (explosive) (82) |
| Au nanostar (69) | Polymer film (58) | Cd2+ (pollutant) (51) |
| Ag nanooctahedra (83) | Microparticle arrays (84) | Pyrene (food contaminant) (85) |
| Au nanoprism (86) | Metal electrode (87) | Crystal violet (dye) (50) |
2.3. Nanoparticle Aggregates: Hotspot Design Strategy
A fundamental scientific challenge in SERS is the interaction of the hotspot with the target molecule. Simply constructing abundant hotspots or positioning molecules near the surface of nanostructures is not sufficient to achieve highly sensitive and stable SERS detection. Therefore, in addition to the classical colloid agglomeration and rough-surface nanostructure film, various methods have been proposed that focus on both building nanostructures and guiding target molecules into plasmonic hotspots.
2.3.1. Dynamic SERS with 3D Hotspot Matrix
To address the challenges such as the low utilization efficiency of hotspots and the poor stability of classical colloidal agglomerations, Yang and colleagues proposed a dynamic SERS detection method based on the state translation of NPs from the wet state to the dry state, with measurements conducted during this process (including solvent and evaporating stages). Additionally, They introduced a 3D hotspot matrix formed during the evaporation process, characterized by minimal particle size polydispersity and maximum distance uniformity between particles (Figure 4a). (88) This 3D matrix can accommodate high-density hotspots, thereby enhancing SERS effect. To maintain the existence time of 3D hotspots, they further employed nonvolatile substances in the presence of glycerol to construct a dynamic SERS system with higher stability. (89) Glycerol with slow evaporation rate protects NPs and target molecules from photobleaching, thereby improving sensitivity and stability (Figure 4b-c). This dynamic SERS method is similar to the droplet levitating platform proposed by Yang et al. (see section 2.4). (90) The presence of the glycerol can also avoid additional laser effects, such as photobleaching, substrate heating or possible changes in substrate morphology. (91)
Figure 4
Figure 4. Dynamic SERS method. (a) Dark-field optical microscopy for real-time tracing of the morphological alterations of a specific aggregate in the evaporation process of a 1 mL sample. This sample of Ag sols was 10-fold diluted with 0.01 mM citrate solution to avoid overly strong light scattering. Reproduce from ref (88). Long-period and high-stability 3D hotspots for the detection of different molecules. SERS spectra obtained at different concentrations of (b1) NOD and (c1) TBZ in 5% glycerol system. Time-dependent Raman spectra of (b2) NOD and (c2) TBZ based on the long period and high-stability 3D hotspot matrix constructed with the assistance of 5% glycerol. (88,89) A liquid-phase SERS method. (d) Reversible O/W encasing for self-assembly of metal liquid-like Au nanorod arrays is realized in a common cuvette. (e) SERS spectra of TBZ with concentrations of 1, 101, 102, 103, and 104 ppm, respectively. (f) A linear plot of r780/662 against logarithmic concentration of pesticide. Reproduce from ref (14). Capillary capturing target molecules into small gaps method. Schematic diagram of the assembled NP film (g1–i1) and high-speed camera picture (g2–i2) from the initial wet stage to final dry stage of the monolayer NP film. (j) SERS spectra collected from a single A549 cell during the cell death process caused by photothermal stimulation. (k) Schematic diagram of the capillary SERS method for in situ monitoring of the single-cell death process under photothermal stimulation. Reproduced from ref (93).
2.3.2. Liquid Phase SERS Method Combining Hotspots Nanostructures Assembly with Measurement
It is well-known that 2D nanoarray assemblies of liquid/liquid and liquid/gas interfaces, as well as the 3D nanoarray assemblies of liquid/liquid interface, offer several advantages, including self-healing ability, variable shape and high mechanical stability. The reversible Oil/Water encasing strategy to self-assemble metal liquid-like 3D arrays could be achieved just by controlling the surface wettability of the containers, as shown in Figure 4d–f. (14) Different from the liquid–liquid self-assembly arrays, Yang and co-workers employed the phase equilibrium principle of a partially soluble triliquid system (solvent/chloroform/acetone) to construct a high-density hotspot matrix for dispersing antitumor drug in the blood. (92) This method enabled NPs to form a highly stable hotspot matrix with tunable particle gaps. Therefore, water-soluble antitumor drugs in blood could be dispersed rapidly and enter the hotspot matrix spontaneously. Liquid SERS analysis improves the hotspot utilization efficiency and dynamic tunability, facilitating the entry and enrichment of target molecules. In addition, trace molecules can be analyzed in either the single solvent phase or the dual-phase (such as the water/oil interface). The molecular reaction process can be controlled by the phase transfer or diffusion in the liquid dual-phase system, enabling the high-sensitivity detection and quantification of reactants, products, and possible intermediates in the liquid phase through SERS spectroscopy.
2.3.3. Capillary Guiding Molecules into Hotspot Nanostructures Methods
The capillary phenomenon, observed in plant ducts, plays a key role in water transport. Inspired by this, transpiration driven by capillary force has shown the potential to help target molecules enter SERS-active hotspots. Yang et al. developed the nanocapillary pumping model, as shown in Figure 4g–k. (93) Nanocapillary pumping, with solvent evaporation, enables rapid and sensitive SERS detection of various analytes. In this process, the abundance of hotspots and the inevitable entry of molecules into them enhance the effectiveness of the hotspots. Nanocapillary pumping method provides a novel way for generating hotspots that actively attract target molecules, and achieving 2–3 orders of magnitude higher sensitivity on a solid SERS substrate. (94) To enhance molecular accessibility to hotspots, Qin et al. designed a three-layer structure with an intralayer gap of ≈8 nm and an interbedded gap of <3 nm. Through capillary force pumping, the target molecules naturally entered into interbedded smaller gaps. (95) Chen et al. proposed a nanopocket model based on the capillary force using a common MoS2–Ag heterostructure. (96) In this model, target molecules were spontaneously introduced into the MoS2–Ag heterogeneous nanopocket structure, resulting in a 3–7 times increase in SERS signal intensity compared to the nanocapillary model. Overall, the strategy of capturing target molecules into small gaps based on the SERS hotspot substrates has proven to be effective and is expected to be further improved.
2.4. Enriching and Delivering Analytes from Solutions into the SERS Hotspot
Au and Ag micro/nanostructured surfaces are extensively utilized as SERS substrates. There are two main approaches for delivering analytes from solution onto the SERS substrates. The first method is to immerse the SERS substrates into the solution containing analytes, which typically requires several hours to reach the adsorption equilibrium. However, this approach is inapplicable to inert molecules with weak affinity to the SERS substrate. The second method is evaporating a droplet containing analytes on the SERS substrates, which results in an inhomogeneous distribution of analyte molecules owing to the “coffee ring” effect, i.e., the ring-like pattern left by the particle-laden liquid after it evaporates. (97) The pinning of the solid/liquid/gas three-phase contact line causes the “coffee ring” effect, leading to the accumulation of analyte molecules around the pinning circle. Generally, the analytes spread over square centimeters even using 10 μL of analyte solutions, while the laser spot used for SERS measurements is only a few micrometers in size. This means that only 1 in 0.1 billion alanyte molecules has the opportunity to be exposed to the laser. Therefore, it is crucial to concentrate analytes from diluted solutions into a tiny dot (ideally, micrometer size) and guide the analytes toward hotspots in an efficient manner after solvent evaporation to enhance the performance of SERS substrates.
Superhydrophobic surfaces can concentrate analytes in water into a spot after solvent evaporation and prevent the formation of “coffee ring”. For example, superhydrophobic surfaces with lithographically fabricated micropillars can concentrate and deliver biomolecules (e.g., lambda DNA, lysozyme) from highly diluted solutions to a specific area covered by an Au or Ag layer, enabling SERS detection even at attomolar concentrations (10–18 mol/L). (98) However, the wetting transition from the Cassie state to the Wenzel state when the droplet size reaches a threshold value (generally, submillimeter size) limits further size reduction of the analyte aggregate. (99)
A series of methods to concentrate analytes and overcome the unevenness in the process has been developed. For example, inspired by the pitcher plants, Yang and co-workers developed the slippery liquid-infused porous surfaces (SLIPS) based SERS platform. (100) SLIPS consists of a micro/nanoporous substrate membrane infiltrated with lubricating fluid, creating a smooth and stable interface that nearly eliminates pinning of the liquid contact line. (101) The interface enriches the analytes from both aqueous and nonaqueous liquids into a tiny spot, enabling ultrasensitive detection at attomolar levels and eliminating pinning effects for detection in various solvents. (100)
However, in the above platform, the lubricant liquid tends to wrap the liquid droplet and can interfere with SERS detection. To avoid this issue, another analyte enrichment and filtration (AEF)-SERS platform was proposed. (35) This platform consists of two key components. First, the molecularly smooth polydimethylsiloxane (PDMS) brush surface exhibits slippery properties due to the negligible adhesion forces between the droplet and the solid surface, facilitating analytes enrichment. The second critical component is the MOF-encapsulated Au nanorods. A thick layer of porous MOFs was grown onto the Au nanorods, to restrict molecules bigger than the pore size from contacting the Au nanorods and to prevent the formation of hot spots between Au nanorods. The reduction in SERS sensitivity due to the absence of SERS hotspots was compensated by the analyte enrichment effect provided by the slippery PDMS brush surface, which can shrink the analyte dispersion area by millions of times compared to common SERS substrates after solvent evaporation. The indiscriminate enrichment of analyte molecules during solvent evaporation poses challenges for identifying analytes in complex samples containing multiple species. The AEF-SERS platform successfully achieved the selective detection of 4-nitrobenzenethiol at nanomolar concentrations in whole blood. This method avoids the use of lubricants, and MOF filter greatly enhances the analyte identification capability in complex samples.
Self-assembled Au NP monolayers are ideal SERS substrates, while it is challenging to concentrate analyte molecules on the self-assembled Au NP monolayers without disrupting the hotspots. To address this, the slippery Au nanosphere monolayers were reported, which could enhance analyte concentration during solvent evaporation without disrupting hotspots. (81) To form these monolayers, a thin silica shell was used to wrap the Au nanosphere monolayer, allowing the subsequent functionalization of the PDMS brush monolayer. The monolayers concentrate analytes into a 3D Au NP/analyte aggregate after solvent evaporation, boosting SERS signals.
Despite these advances, it is challenging to concentrate all analytes into the final aggregate on slippery surfaces, as residues inevitably form due to wetting defects or evaporation. To overcome this, Yang et al. introduced the acoustic levitation technique into the SERS sensing system, enabling lossless analyte concentration from volatile liquids, solids, or air, facilitating multiplex and multiphase detection at femtomolar levels (Figure 5a). This droplet-levitating enrichment platform overcomes the limitations of slippery surfaces, achieving 20,000 times analyte enrichment and allowing sensitive SERS detection even at attomolar levels (Figure 5b). (90) The combination of this strategy and the nanoporous Ag microparticle SERS substrates (39) have the potential to provide fingerprint information on the molecule of interest with high sensitivity down to a single molecule level, expanding its applicability in the early diagnosis of diseases.
Figure 5
Figure 5. Scheme of enrichment process of dye molecules. (a) Schematic of the multianalyte and multiphase enrichment using the acoustic levitating platform and the consequent multiplex and multiphase SERS detection. (b) Enrichment process of dye molecules from 10 μL of ethanol solutions. Reproduced from ref (90). Copyright 2022, The Authors.
3. SERS Substrates: Solid Substrates
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3.1. 3D Plasmonic Hydrogel Structures
Hydrogels are interesting supports for a wide variety of applications. Their huge capacity to absorb and expel water offers plenty of possibilities for trapping molecular and even nanomaterials. For this reason, hydrogels have been combined with metal nanoparticles to fabricate nanocomposite materials with enhanced functionalities, including SERS sensing. In an early example, it was demonstrated that hydrogels loaded with Ag NPs could readily adsorb analyte molecules, which would be readily detected upon drying because of the reversible creation of hot spots between approaching Ag NPs. (102) Such a dynamic hot spot creation was possible thanks to the properties of the hydrogel and the uniform distribution of the nanomaterial. This review focuses here on the use of hydrogels for biomedical applications, mainly related to 3D cellular models of the real tissue.
Advances in biomodel design and additive manufacturing techniques, including 3D bioprinting, have motivated the implementation of monitoring techniques that are compatible with these biologically elaborate environments. The development of materials for biomodels must consider physical (stiffness, viscoelasticity, porosity), chemical (ionic strength, pH, hydrophilicity, biodegradability), and biological (biocompatibility, cytotoxicity, adherence) properties, aiming to support eukaryotic or prokaryotic growth, differentiation, maturation, and diffusion. While some of these properties are inherent to the biomaterial itself, through synthetic methods, additional functionalities can be incorporated resulting in highly optimized materials that also fulfill the required properties for 3D printing (e.g., thixotropic behavior, noncytotoxic gelling). With a special focus on hydrogels, although naturally derived hydrogels (e.g., alginate, collagen, agarose) typically display high chemical and biological compatibility, they have poor physical properties, which limits their use in 3D printing applications. Synthetic hydrogels, in contrast, often show poor biocompatibility, either due to the biological composition or their inflexible nature to cell-directed restructuring. A variety of materials and hybrid hydrogel-nanomaterial fabrication methods have been recently reviewed. (103) Aiming to study temporal and spatial changes within these complex biological models in a noninvasive manner, our attention is drawn to techniques that employ noninvasive interrogation methods and allow multiplexing (i.e., observation of multiple compounds/biomarkers in a single measurement). As presented in previous sections, SERS is an excellent choice to achieve these goals, featuring the use of near-infrared (NIR) excitation wavelengths for bioimaging or detection of Raman-active (bio)molecules. An attractive approach is the use of “SERS nanotags”, i.e., plasmonic NPs such as Au nanostars or nanorods, coated with Raman reporter molecules and an outer polymeric shell (see section 4 below) that improves stability in biological environments and can be used to provide cellular targeting. (104) SERS nanotags can be readily incorporated into naturally derived or synthetic hydrogels, providing a SERS-active substrate that can be deposited or printed in a variety of geometries. More details about SERS nanotags will be discussed in section 7. Alternatively, the incorporation of bare Au nanostars or nanorods can be used for the label-free detection of Raman-active biomarkers with high spatial resolution. However, conducting SERS in biological environments carries an intrinsic complication due to protein fowling and potential loss of SERS signal intensity and peak resolution. (105)
For the design of hydrogel scaffolds, incorporation of plasmonic NPs in the hydrogel composition requires optimization of their concentration, to achieve meaningful signals in direct SERS sensing. In a recent example, it was shown that increasing Au nanorod concentration led to increased SERS signal for 3D mapping based on the peak at 1083 cm–1 from 4-mercaptobenzoic acid (MBA), whereas excessive absorption (opacity) and scattering (turbidity) of light by Au nanorods significantly hindered SERS intensity (Figure 6a). This impaired penetration effect becomes more relevant at increasing depth into the 3D biomodel, which remains an important issue in SERS bioimaging. (105,106) However, SERS achieves substantially better penetration depth than the current gold standard technique, confocal fluorescence microscopy (CFM), reaching over 1000 μm in depth in direct SERS detection, both in bare hydrogel structures and in those containing cells. (107) This improved light penetration is possible because in Raman microscopy one can readily use longer excitation wavelengths, e.g., 788 nm (within the first biological transparency window) when Au nanorods or Au nanostars are used as plasmonic substrates. On the other hand, by working in the biological transparency window, the hydrogel itself allows transmission of light with longer wavelengths because of reduced scattering and negligible water signal. (108) In terms of xy resolution in hydrogels, equivalent spatial distribution has been demonstrated for imaging of breast cancer tumoroids using CFM and SERS. (106) In this case, a heterogeneous cell population was used, which was labeled with both fluorophores and SERS nanotags; both CFM and SERS microscopy could image the same region of a hydrogel scaffold designed to support tumoroid growth (Figure 6b). Again, because SERS can penetrate deeper into biological models, cell migration could be observed in regions that would otherwise not be distinguished using CFM. (107) Due to the relatively recent application of SERS as an imaging technique for complex 3D biomodels, it is important to prove the temporal and spatial correlative nature of CFM and SERS, so that SERS can be established as a reliable technique for in situ bioimaging.
Figure 6
Figure 6. Raman imaging of SERS hydrogels. (a) 2D imaging of the SERS intensity at 1083 cm–1 in hydrogels with different Au nanorod concentrations: (i) 0.1 mM, (ii) 0.5 mM, (iii) 1 mM, and (iv) 1.5 mM, respectively. Adapted with permission from ref (105). Copyright 2020, John Wiley and Sons. (b) Comparison between the CFM imaging and high-spatial-resolution SERS imaging of the hydrogel scaffold supporting SERS nanotag-labeled tumoroids. Adapted with permission from ref (106). Copyright 2024, The Authors.
A key advantage of SERS nanotags is the potential to create a library to label multiple cell populations. (109) When applying such a library, it is important to correctly match SERS tag intensity with respect to relative cell uptake and cell number in mixed cell populations. In other words, “bright” SERS nanotags should combined with cells present in low numbers, whereas “dim” SERS nanotags should be used for cells in high numbers or with high levels of endocytosis (i.e., phagocytic cells). This method was recently applied to label different cell types in a 3D printed mimic of human skin, modeling melanoma. (110) In this case, the brightest SERS nanotags were used to follow metastatic cell movement across a basement-membrane, prelabeled with a separate and distinguishable SERS tag. As it happens, theory and practice may offer conflicting results, and whereas multiplexing using SERS nanotags can be readily achieved in 2D cell cultures, (111,112) application in 3D models containing biomolecules and scattering components may lead to complications in distinguishing each SERS signal. Fortunately, accurate spectral analysis by machine learning can be used to enhance the signal-to-noise ratio, particularly along the z-axis. (104,110)
Anisotropic plasmonic NPs can also be used for direct SERS in hydrogels, e.g. to monitor the diffusion of cytotoxic drugs (113) or the presence of tumor-associated biomarkers. (106) Here, the potential of SERS as a 3D spectral imaging technique truly shines, as molecules lacking fluorescent emission can be clearly located with spatial and temporal resolution (termed 4D imaging). Again, the importance of minimizing scattering by the host material is paramount. In studies where hydrogel scaffolds containing Au nanorods were filled with cells and extracellular matrix, SERS sensitivity was often reduced in all imaging planes (xyz). (113) Some other aspects should be considered when applying hydrogels loaded with Au NPs. On one hand, reduced SERS signals might result from reshaping or aggregation of anisotropic NPs in biological environments, which can be monitored by UV–vis-NIR spectroscopy and electron microscopy. (104,106,114) Additionally, it has been reported that incorporation of Au nanorods may affect the rheological properties of hydrogels. Although some works report on reinforced hydrogel networks upon addition of inorganic NPs to polymer gels, the general observation is that such hybrid materials must be optimized and well characterized over a range of NP concentrations. (115) For example, addition of Au nanorods at a final concentration of 0.5 mM (Au0) to hydrogels made of methacrylated hyaluronic acid (HAMA) was shown to reinforce the viscoelastic nature of the hydrogel matrix, but no further improvements were noted above 0.5 mM. (105) Similarly, the recoverability of synthetic inks based on polyethylene glycol diacrylate (PEGDA) was shown to be dependent on the concentration of incorporated Au nanorods. (114)
3.2. Nanoparticle Metal Organic Frameworks
Direct SERS analysis in complex fluids, or direct measurements in the sample media upon contacting the plasmonic materials, is often constrained by the nonspecific coadsorption, onto metallic nanostructures, of other species in the matrix solution. (116,117) Such undesired events can significantly increase the complexity of the vibrational assignment or even completely prevent the interaction with the target analyte. Thus, it is of utmost importance to design new plasmonic substrates capable of inhibiting the competitive adsorption of nontargeted elements on the active surfaces. (118) In the case of real biological or environmental samples, a myriad of elements contributes to the final composition, including inorganic ions, cells (i.e., sample cells, bacteria, fungi and algae, etc.) and large molecules such as proteins, lipids, polysaccharides, biofilms, nucleic acids, humic and fulvic substances and other molecules originated from the metabolism of the life (i.e., cells, plants, fish and other animals). At the same time, anthropogenic factors related to human activities (agricultural, industrial, domestic, etc.) can also play a key role in determining the quality of natural samples.
As a large fraction of the species in natural waters or biological fluids are large, their interaction with the plasmonic surface can potentially be restricted by using additional components with molecular sieving properties. These materials may range from porous polymers to inorganic oxides. (118) Thus, it has been very common to coat plasmonic NPs with porous silica (Figure 7a). (119) This approach, however, presents some drawbacks. For example, it is known that single spheres, (120) the most common material, present limited electric film to enhance the Raman signal. To address this issue, other NPs capable of behaving as single hotspots (i.e., nanostars) have been used. (121) Notwithstanding, this approach still encounters some challenges. The fact that the silica coating is in direct contact with the plasmonic material restricts the ability of the optical enhancer to interact with the analytes. To resolve this issue, the use of yolk shells, where the plasmonic materials are separated by a void from the coating, has been employed─for example, with nanostars (Figure 7b). (122) Alternatively, films of NPs deposited on discrete microparticles of polystyrene, to form dense collections of hot spots, that are posteriorly coated with mesoporous silica and converted into hollow capsules through the dissolution of polymer core had been also successfully developed (Figure 7c). (123,124) These strategies have led to advanced functional materials with improved operation in complex samples (125,126) but still exhibit some limitations. First, the pore size is not easily controllable, and second, while these materials may sieve large cellular or molecular entities, they do not impose restrictions on the myriads of small molecules that may be present in the sample. (122)
Figure 7
Figure 7. Fabrication of MOFs. (a) TEM images of Au spherical particles coated with a homogeneous silica shell. Of 98.5 ± 7.0 nm. Adapted with permission from ref (119). Copyright 2009, American Chemical Society. (b) TEM images of a single Au nanostar mesoporous silica coated yolk shell. Adapted with permission from ref (122). Copyright 2019, Royal Society of Chemistry. (c) SEM and TEM/XED analysis of mesoporous silica shells containing Au island films in their interior. Adapted with permission from ref (123). Copyright 2019, John Wiley and Sons. (d) SEM image of core–shell Au nanostars coated with MOF (ZIF-8). Adapted with permission from ref (133). Copyright 2019, John Wiley and Sons. (e) TEM image of yolk shell Au nanostars coated with MOF (ZIF-8) after dissolution of the inner ZIF-67. Adapted with permission from ref (128). Copyright 2023, John Wiley and Sons. (f) STEM images (bright and dark field) for PS@Ag, Ag@ZIF-thin, and thick plasmonic-MOFs. Adapted with permission from ref (135). Copyright 2024, John Wiley and Sons.
In this scenario, plasmonic MOFs have emerged as a significant area of research in the field of SERS, primarily due to their unique structural properties and the ability to enhance Raman signals through localized surface plasmon resonance (LSPR). (127) The incorporation of MOFs into this system provides additional benefits, such as high surface area, tunable pore sizes, shapes and chemical environment, and the ability to selectively capture target analytes, which further enhances the SERS performance. (128,129) Recent studies have demonstrated that the structural characteristics of MOFs can be tailored to optimize their interaction with plasmonic NPs. For example, the design of core–shell structures, where plasmonic NPs are encapsulated within a MOF shell, has been reported to enhance the stability and sensitivity of SERS substrates. (130,131) This configuration not only protects the NPs from environmental degradation but also allows for a more controlled interaction with target molecules, leading to improved SERS signals. Additionally, the high porosity of MOFs enables the efficient diffusion of analytes into the framework, facilitating their interaction with the plasmonic surface. (132) Notwithstanding, plasmonic MOFs are subject to the same drawbacks of generation of electric field enough to yield adequate SERS signals. Thus, analogous as with the silica coatings, nanostars core/shells (Figure 7d), (133) yolk shells, prepared upon the use of two different MOFs, the inner soluble in water and the outer insoluble (Figure 7e), (128) or plasmonic films on discrete polystyrene beads (Figure 7f), (134) had been extensively used as plasmonic cores.
The versatility of MOFs extends to their functionalization, which can be achieved through postsynthetic modifications. This allows researchers to tailor the chemical environment of the MOF to enhance its affinity for specific analytes, thereby improving the selectivity and sensitivity of SERS detection. (136,137) For instance, the incorporation of functional groups into the MOF ligands can promote stronger interactions with target molecules, leading to enhanced Raman signals. Furthermore, the ability to modify the pore size and surface chemistry of MOFs enables the selective capture of analytes based on their size and chemical properties, which is particularly advantageous in complex sample matrices (138) or even to classify between chiral molecules. (139,140)
The application of plasmonic MOFs in SERS has been successfully demonstrated in various studies. For example, MOF coated Ag NP was used for the sensitive detection of pesticides in apple samples. (141) Similarly, the development of a three-dimensional MOF-based SERS platform has shown promise for real-time atmospheric monitoring, highlighting the potential of these materials in environmental applications. (142,143) The hydrophobic nature of certain MOFs can be engineered to enhance their interaction with nonpolar or weakly polar analytes. This modification is crucial for enhancing the interaction between the analyte and the plasmonic surface, as it allows for a greater concentration of target molecules in proximity to the SERS-active sites. Additionally, studies have demonstrated that the hydrophobicity of MOFs can be adjusted through various synthetic strategies, such as incorporating hydrophobic organic ligands, which further enhance their ability to trap hydrophobic guests. (144) This property has been effectively utilized to create molecular traps that facilitate the detection of analytes that typically lack a SERS signal due to insufficient interaction with plasmonic surfaces. (134) The use of ion-selective dyes as chemosensors rather than as analytes (145) represents a novel approach in the development of SERS-based sensors for transition metals. By leveraging the tunability of MOFs and their ability to selectively capture specific ions, it is possible to design sensors that exhibit enhanced SERS signals for transition metal detection. This method capitalizes on the interaction between the analyte and the plasmonic substrate, which is crucial for generating detectable Raman signals (Figure 8a). (134) Moreover, the integration of MOFs with plasmonic materials has opened new avenues for the development of multifunctional sensing platforms. For instance, by leveraging the hydrophobic properties of MOFs in combination with the photothermal excitation of gold nanostars within the biological window, it is possible to create a drug delivery scaffold that can simultaneously monitor the release kinetics using SERS. This can be achieved by employing the same light source both for the generation of heat and for subsequent drug release through thermal diffusion (Figure 8b). (133) Also, the combination of MOFs with other nanomaterials, such as carbon-based materials or metal oxides, can lead to enhanced SERS performance while also providing additional functionalities, such as photocatalytic activity or electrochemical sensing capabilities. (132,146) This multifunctionality is particularly beneficial in complex sensing scenarios where multiple analytes need to be detected simultaneously. In fact, this photocatalytic process can also be directly achieved by using the MOF as the catalyst and illuminating the plasmonic material with visible light to generate hot electrons. By using the same light source for both the catalytic process and SERS monitoring, in an operando spectroscopy setup, it is possible to obtain direct and detailed information on the kinetics and catalytic mechanisms involved (Figure 8c). (135)
Figure 8
Figure 8. Applications of SERS MOFs. (a) (i) SERS spectra of different concentrations of bathocuproine adsorbed on PS@Ag@ZIF-8. (ii) SERS spectrum of the sediments obtained after several washing cycles. (iii) Comparison between the SERS intensities of bathocuproine (band at 1377 cm–1) on PS@Ag@ZIF-8 and PS@Ag after the same washing samples. (iv) SERS spectra of bathocuproine on PS@Ag@ZIF-8 upon immersion into Cu(II) solutions in PBS buffer at different copper concentrations (from 38 to 254 ppb). Adapted with permission from ref (134). Copyright 2023, American Chemical Society. (b) (i) SERS spectral kinetics acquired on a nanostar coated with MOF and loaded with a nucleus dye (Hoechst 33258, HOE) with and without NIR illumination (785 nm); solid and dashed lines represent the time points 0 and 8 h, respectively. Kinetics was built with the SERS intensity of the ring breathing mode of HOE (980 cm–1). (ii) White light image (top) and SERS images of a single cell with the MOF composite time 0 (middle) and after 8 h of irradiation (down). (iii) Confocal microscopy image of cells incubated with core–shell containing HOE before and after NIR treatment. Blue and orange colors represent HOE and cell membrane staining (CellMask Deep Red), respectively. Adapted with permission from ref (133). Copyright 2019, John Wiley and Sons. (c) Photocatalytical degradation curves of rhodamine B under green illumination. Intensity corresponds to band 1202 cm–1. SERS spectra are presented as a 3D graph to guide the diminishing of the intensity across the full spectrum. Adapted with permission from ref (135). Copyright 2024, John Wiley and Sons.
Plasmonic MOFs represent a promising class of materials for enhancing SERS detection capabilities. Their unique structural properties, coupled with the ability to tailor their chemical environment, provide significant advantages in terms of sensitivity, selectivity, and stability. As research in this field continues to advance, it is expected that plasmonic MOFs will play a pivotal role in the development of next-generation sensing technologies across various applications.
3.3. Semiconductor SERS Substrates
Semiconductor materials that exhibit low toxicity and good biocompatibility serve as ideal candidates for the investigation of biologically relevant systems. (147) To date, a variety of semiconductor materials have been demonstrated to exhibit SERS activity, including metal oxides, metal sulfides, metal nitrides, element semiconductors, and organic semiconductors. (148) The design of semiconductor substrates with high enhancement factor is a primary challenge that must be addressed for the development of semiconductor SERS-based applications. In this regard, the first aspect to consider is the enhancement mechanism. Similar to metal SERS, the Raman signal of a molecule on the semiconductor surface is also enhanced through the generating of charge-transfer (CT) transitions and/or the amplifying electric fields. (149−151) The strategies to design and optimize SERS-active semiconductor substrates based on these two enhancement mechanisms are presented below.
3.3.1. Semiconductor Substrates Based on CT Mechanism
In theory, Herzberg–Teller vibronic coupling enables the Raman scattering of a molecule to borrow intensity from CT transitions between the molecule and the semiconductor. (152) Therefore, creating CT routes that resonate with incident photons is crucial for enhancing the CT contribution to SERS. Several strategies involving the introduction of intermediate energy levels within the bandgap have been proposed: (1) introducing surface defects through doping or nonstoichiometric synthesis to enhance the CT interactions at the semiconductor–molecule interface; (153−155) and (2) increasing the electronic density of states by utilizing amorphous semiconductor nanostructures to improve CT efficiency. (156) Besides, creating multiple CT coupling pathways by integrating exciton and/or molecular resonances can further enhance the CT contribution to SERS. (157,158)
In addition, several new modulation methods have emerged to develop sensitive SERS-active semiconductor substrates based on CT mechanism. (159−162) For example, improving the separation of photogenerated electron–hole pairs through semiconductor/semiconductor heterojunctions has demonstrated a promising pathway. (159−161) The formation of the TiO2/ZnO heterojunction results in strong coupling at the interface between the two semiconductor materials, (159) which facilitates an efficient separation of photogenerated electron–hole pairs, which can be supported by photoluminescence spectra and electrochemical impedance spectroscopy. The accumulation of photogenerated electrons enhance the CT efficiency and SERS activity. Furthermore, a TiO2-x facet heterojunction with abundant oxygen vacancies has been shown to boost CT efficiency, enabling ultrasensitive detection and photocatalytic degradation of various antibiotic residues in real water system. (161) In addition, another innovative approach to further enhance CT efficiency has been proposed by drawing inspiration from the modulation techniques employed in dye-sensitized solar cells. (162) This method involves the use of lithium ions to modulate TiO2 nanostructures, which has been demonstrated to enrich the surface states and lower the conduction band edge of TiO2. Such modulation facilitates the CT interaction between the molecule and TiO2, resulting in an enhancement factor approximately 100 times greater than that of pure TiO2 substrates.
3.3.2. Semiconductor Substrates Based on Electromagnetic Mechanism
Recently, studies on the electromagnetic mechanism of semiconductor SERS have achieved considerable progress. Unlike metals, which exhibit LSPR due to their high density of free electrons, semiconductors primarily achieve electromagnetic enhancement through morphological and structural optical effects, such as light trapping, subwavelength focusing, and Mie resonance. In theory, efficient electromagnetic enhancement around semiconductor materials typically requires semiconductors with a high refractive index, along with a small imaginary part of their dielectric functions. For example, simulation results indicate that the electromagnetic field induced by Mie resonance in spherical silicon can reach an intensity equal to or even greater than that of gold plasmons at specific particle sizes. (163)
Semiconductor with specific micro/nanostructures can effectively regulate the near-field optical properties. For instance, a TiO2 electrode with a nanotubular geometry can concentrate electric fields within the nanostructures due to scattering and interference effects. (164,165) Additionally, a core/shell resonator composed of SiO2/TiO2 beads was created through the precise deposition of an ultrathin anatase TiO2 layer on the surface of SiO2 NPs. (166) The differences in refractive index between the SiO2 core and the TiO2 shell facilitate the total internal reflection of light within the shell layer. Concurrently, the electric field generated by multiple light scattering significantly amplifies the Raman scattering of analytes adsorbed onto the resonator surface. Similarly, a TiO2 inverse opal structure demonstrates improved SERS sensitivity through the multiple light scattering effect observed in the photonic microarray. (167)
3.3.3. Semiconductor substrates based on multiple enhancement mechanism
In the visible and NIR regions, near-field optical effects typically require the semiconductor materials with feature sizes ranging from submicrometers to micrometers. However, efficient CT transitions usually occur in semiconductor-molecule systems at the nanometric scale. Therefore, the rational design of semiconductor superstructures offers an effective approach to integrate these two enhancement mechanisms. In this context, the ZnO superstructure model (Figure 9a) presents an opportunity to incorporate multiple resonance effects, including CT resonance, Mie resonance, and molecular resonance (Figure 9b, c). (168) The submicron superstructures are constructed from small-sized nanocrystals, which can generate electromagnetic field enhancement due to the Mie resonances. Simultaneously, the nanocrystals can significantly enhance CT transitions owing to the size-dependent electronic properties in semiconductors. Furthermore, the ZnO superstructure coated with ZIF can further amplify the local electromagnetic field surrounding the particle surface, rendering it suitable as a sensing platform for the sensitive detection of volatile organic compounds. (169)
Figure 9
Figure 9. ZnO superstructures and related optical properties. (a) Diagram that illustrates the microstructure of a ZnO superstructure comprised of closely packed nanocrystallites. (b) The comparison of enhancement factor and near-field scattering efficiency observed on ZnO superstructures with different diameters under the 532 nm excitation. Inset shows the corresponding SEM and electric-field distribution images of ZnO superstructures. (c) Potential CT transition pathway and vibronic coupling mechanism. Adapted with permission from ref (168). Copyright 2019, Wiley-VCH Verlag.
Besides, a hollow multishelled V2O5 microstructure has been demonstrated to enhance the sensitivity of semiconductor SERS. (170) This enhancement arises from the unique multishelled configuration, which facilitates multiple reflections of electromagnetic waves, thereby providing efficient resonant absorption for CT and exciton enhancement. Furthermore, the coupling of the outer and inner shells significantly contributes to a heightened electromagnetic field, further promoting SERS enhancement. Very recently, a novel method for the large-area fabrication of TiO2 microspherical arrays has been proposed, combining flame thermal-assisted synthesis with screen-printing technology. (171) This method represents the simplest strategy among the reported SERS-active semiconductor substrates, yet its achieves high sensitivity by integrating multiple synergistic resonances, including Mie resonance, CT resonance, and molecular resonance.
3.3.4. Applications of Semiconductor Substrates
The expansion of SERS-active semiconductor substrates with high performance provides new opportunities for the development of SERS applications. Notably, several SERS-active semiconductor substrates also demonstrate a variety of catalytic activities, such as photocatalysis, electrocatalysis, and nanozyme catalytic functions. (172−174) For a comprehensive discussion on these applications, we recommend the recent review by Itoh et al. (151) Here, we will introduce the direction for semiconductor SERS in catalysis.
Recently, a unique class of nanomaterials capable of mimicking enzyme functions and demonstrating substantial potential in biomedical detection. (175) The careful design and construction of semiconductor nanomaterials that integrate both SERS and nanozyme effects possess significant implications for ultrasensitive nanozymes-based detection. (176,177) Song et al. have constructed reduced MnCo2O4 nanotubes that serve as efficient SERS substrates with oxidase-like catalytic properties. (178) By establishing a kinetic model for SERS detection of nanozyme catalysis, they found that the affinity of the SERS kinetic strategy is greater than that measured by ultraviolet–visible absorption spectroscopy. This finding suggests that SERS technology can provide ultrasensitive monitoring of the catalytic processes of single-layer molecules at catalyst active sites, thereby laying the foundation for ultrasensitive detection of nanozyme catalysis. Additionally, Song et al. constructed NiCo2S4 transition metal sulfide nanosheets, which exhibit excellent laccase and SERS activity, demonstrating great potential for detecting various catechin molecules. (179)
In addition, Huang et al. constructed biodegradable nanozymes based on γ-MnOOH, demonstrating that the oxidase-like properties of γ-MnOOH nanowires can decompose into inactive Mn2+, thereby enabling ultrasensitive detection of acetylcholinesterase, methomyl, and dichlorvos. (180) Yin et al. developed a single-atom nanozyme, Fe-SA/Ti3C2Tx with peroxidase activity, which also exhibited SERS activity. Through linear discriminant analysis and heatmap data analysis, they achieved the simultaneous identification of five antioxidants: ascorbic acid, uric acid, glutathione, melatonin, and tea polyphenols. (181) Li et al. constructed Mo2N NPs with exceptional peroxidase activity and SERS activity, enabling indirect SERS detection of glutathione, alpha-fetoprotein, and carcinoembryonic antigen in serum samples. (182) Yang et al. prepared biocompatible Cu3SnS4 nanosheets, which generated a substantial amount of reactive oxygen species, mediating oxidative damage to cells under visible light irradiation and facilitating photothermal disruption of bacterial membranes under NIR irradiation, to advance antibacterial therapies. (183) The innovative properties of these SERS and nanozymes provide significant advantages for potential applications in biomedical detection and diagnostics, with their enhanced sensitivity and efficiency poised to revolutionize disease diagnosis and management.
4. SERS Nanotags
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4.1. Fundamentals of SERS Nanotags
SERS nanotags (also known as SERS nanoprobes or SERS NPs) are engineered NPs designed to enhance Raman signals for sensitive detection of biomolecules. They typically consist of four components: noble metal NPs, Raman reporter molecules, a protective layer, and a modification layer (Figure 10). (184) The noble metal NPs serve as the enhancement substrates, to amplify the Raman signal of the reporter molecules through electromagnetic field and/or chemical enhancement mechanism. Since noble metal nanostructures with different morphologies exhibit varying SERS enhancement capabilities, it can effectively optimize the SERS performance of nanotags by rationally designing the morphology of metal substrate. Nanospheres and nanorods are the most used materials. Also, SERS substrates with different morphologies have been investigated to maximize enhancement performance, such as nanostars, nanocages, nanoflowers, and nanowires. (185,186) By constructing sharp tips, corners, or internal gaps on the surface of NPs, more hotspots can be generated, leading to a significant increase in Raman signal intensity.
Figure 10
Figure 10. Typical fabrication process of SERS nanotags: noble metal NPs, Raman reporter molecule adsorption, protective layer coating, and modification layer attachment.
The metallic core is usually coated with Raman reporter molecules that provides a distinct spectral fingerprint, allowing for easy identification. Raman reporter molecules typically have large Raman cross sections and are adsorbed onto the NP surface by self-assembly chemical or electrostatic interactions. Fluorophores with an absorption wavelength close to the laser excitation wavelength have been widely used. Because their signals are further enhanced by SERRS, they are known as resonance Raman reporter molecules. (187) They provide higher Raman signals but also increase fluorescence background. Small organic molecules containing thiol or amino groups show lower background and high affinity to the metal substrates. Their characteristic peaks are distinct and easily assigned, minimizing overlap with the spectral bands of other Raman reporter molecules. In recent years, “orthogonal Raman reporter molecules” with Raman features in the biological silent region (1800–2800 cm–1) range have been reported (discussed in section 4.3). These molecules typically exhibit vibrational modes of functional groups such as alkynes, nitriles, and azides. By avoiding interference from biological background peaks, they provide distinguishable peak information.
The protective layer increases the stability and biocompatibility of the nanotags. Common materials for the protective layer include biomolecules (liposome, phospholipid coating layer, bovine serum albumin), silica (solid or mesoporous silica layer), polymers, thiol-PEG, dopamine, MOF, etc. More information about the protective layer can be found in a related review. (188) At present, thiol-PEG is the most widely used, which can be designed to have carboxylic acid groups or amine group at another terminal of molecular structure. In recent years, biomimetic protective layers with conjugated biomarkers are also developed, including cell membrane, and exosome coatings (discussed in section 4.5).
The modification layer, on the other hand, involves the attachment of biorecognition molecules to enable the nanotags to bind to target biomolecules with high specificity and affinity. These biorecognition molecules include oligonucleotides, antibodies, peptides, and aptamers. The affinity of biomolecules to SERS nanotags could be electrostatic or chemical interactions. For example, negative electronic antibodies can be immobilized with poly-l-lysine modified plasmonic cores for surface coating. Carboxy-reactive groups and primary amine groups can cross-link to form amide bonds in the presence of 1-ethyl-3-(3-(dimethylamino)propyl) carbodiimide (EDC) and N-hydroxysuccinimides (NHS); this method is usually used to modify, label, cross-link or immobilize peptides, proteins, antibodies, and oligonucleotides through their 5′ phosphate groups to the surface of nanotag’s protective layer.
4.2. SERS Nanotags with Interior Gaps
As a novel type of SERS nanotags, gap-enhanced Raman tags (GERTs) with built-in Raman reporters have attracted much attention in recent years. (189) The structure of the GERT typically consists of a metal core, a metal shell and a Raman-active isolation layer in between (Figure 11a). GERTs exhibit the following advantages: ultrahigh brightness with enhanced plasmonic enhancement within the interior gaps; (190,191) excellent colloidal stability and signal photostability, as the Raman reporter molecules are protected by metallic shell structures; stable SERS responses even in an aggregated state, which holds potential in quantitative Raman analysis; suitable for multiplexed encoding by embedding multiple Raman molecules in the internal gap, or different Raman molecules in different gap layers for multishell GERTs. (192) Due to their superior performance, GERTs have been widely used in areas such as information security, (193,194) fast imaging, (195) biosensing, (196−199) in vivo detection and imaging, (200−203) and multifunctional theranostics. (204−206) To fabricate GERTs with high sensitivity, specificity, and stability, the rational design of the internal gap structure, selection of Raman reporter molecules and substrate materials, and control of particle morphology are required.
Figure 11
Figure 11. Characterization and formation mechanism of GERTs. (a) Geometrical illustration of a GERT. (b) The molecular structures, (c) TEM images, and (d) SERS spectra of GERTs with different organic molecules embedded. Reproduced from ref (194). Copyright 2020, The Authors. (e) GERTs with interior gaps of different thickness. Reproduced from ref (211). Copyright 2018, American Chemical Society. (f) Growth mechanism illustration using molecular dynamics simulation. Reproduced from ref (212). Copyright 2021, American Chemical Society. (g) Different core morphologies of GERTs. (i) Petal-like shell GERTs. Reproduced from ref (203). Copyright 2019, The Authors. (ii) Au bipyramid GERTs. Reproduced from ref (214). Copyright 2024, The Authors. (iii) Au nanotriangle GERTs. Reproduced from ref (215). Copyright 2019, American Chemical Society. (iv) Dual-gap nanodumbbell GERTs. Reproduced from ref (216). Copyright 2023, Wiley. (v) Multishell nanorod GERTs. Reproduced from ref (217). Copyright 2016, Elsevier. (vi) Au petal-like core with Ag shell GERTs. Reproduced from ref (218). Copyright 2023, The Authors.
4.2.1. Designing Interior Gaps of GERTs
The internal gaps of GERTs are typically in the subnanometer to few nanometer range. The size of the internal gap in GERTs determines the plasmonic coupling between the metal core and the shell, as well as the near-field enhancement within the gap structure. Several methods for fabricating ultrasmall internal gap structures have been reported and can be divided into two main categories. In the first category, the gap structure is hollowed out by a galvanic exchange reaction between Au and Ag to make a hollow intrananogap when the Au shell is fabricated, and the nanogap can be further filled with Raman-active molecules preadsorbed onto the Au core. (207) However, it is usually difficult to reduce the gap size to subnanometer level using this method. The second and more widely used method involves the preparation of a metal core, then an isolation layer is elegantly deposited around the core to form a junction with subnanometer to nanometer thickness and to separate the core and shell. After the high coverage of the insulating layer around the core, a secondary metallic layer (shell) is formed by direct reduction of the metal on the surface of the insulating layer until the core is completely encapsulated. Materials that have been reported as isolation layers include oligonucleotides modified with fluorescent dyes, Raman-active polymers, and aromatic small molecules. (208,209) These intermediate layers also serve as the source of Raman signals for the entire particle.
The synthesis of embedded Raman-active isolation layers with high precision, yield, and batch–batch reproducibility is critical for the successful fabrication of GERTs. The specially designed oligonucleotide chains modified with fluorescent molecules, (190) while effective as the insulation layers, are limited by cost and availability, making large-scale production difficult. Aromatic Raman-active polymers as the insulation layer also demonstrate uniform signals; (208) they are relatively cost-effective, but not widely or commercially available. In contrast, small aromatic organic molecules are accessible, inexpensive, and feasible. They have strong metal affinity, with functional groups such as thiols, amines, or carboxyl groups that allow direct modification of the metal surface, simplifying synthesis. (194) Therefore, the fabrication of the interfacial layer using the organic molecules remains the most robust and feasible method. Figure 11b–d shows the molecular structures, TEM images, and Raman spectra of GERTs with different organic molecules embedded. (194)
Studies have shown that the layer of embedded Raman reporter molecules is a key factor in the formation of the gap structure, with the thickness of the molecular layer directly determining the gap size. (210) To explain this, GERTs embedded with 1,4-benzenedithiol (BDT) could be used as an example. The 1,4-BDT molecule contains two thiol groups that allow the molecules to form disulfide bonds with each other. When 1,4-BDT is mixed with an Au core for a sufficient time, the molecules self-assemble into a multilayer structure on the Au surface. By controlling the mixing time of 1,4-BDT and the Au core, molecular layers of different thicknesses can be obtained. After growing the Au shell, GERTs with different gap sizes can be fabricated (Figure 11e). (211) In short, optimizing the gap size parameters during synthesis provides a strategy for fabricating GERTs with better Raman performance. Molecular dynamics simulations further confirmed that the surface molecular layers of different thicknesses are compressed during shell growth, changing their orientation and stacking patterns; this results in the formation of gap structures of different thicknesses (Figure 11f). (212)
The introduction of resonance Raman reporter molecules can further increase the sensitivity of GERTs, but these molecules often produce strong fluorescence backgrounds when in resonance with the laser, which can interfere with biological detection and imaging. In recent years, orthogonal-GERTs by embedding alkyne and deuterium-based molecules in the interior nanogaps were developed. (213) They provide characteristic Raman peaks in the 1800–2800 cm–1 range, showing improved photostability and biological stability and background interference-free capability, leading to accurate quantification onto various substrates and in complex media. For example, Au nanorod-based GERTs with embedded 4-mercaptobenzonitrile (4-MBN) molecules have been reported for sentinel lymph node imaging free from interference from light and tissue background. (200)
4.2.2. Design of the Core and Shell Structure
The regulation and design of the morphology of the plasmonic noble metal core or shell in GERTs are of great significance for obtaining highly active GERTs substrates. To fabricate GERTs, the critical step is to select a metallic core, which determines the number of SERS hot spots and provides the space for Raman reporter adsorption. The factors should be considered include the core size, monodispersity, and their capability for robust conjugation with isolation layers. At present, the most common studied GERTs were spherical core–shell structures, using Au or Ag nanospheres as the core. Compared to spherical GERTs, the petal-like multibranched shell structure (Figure 11g, i) provides higher enhancement factors, as the gap structures between the petals offer the more electromagnetic hotspots. Those petal-like GERTs facilitates fast Raman imaging (219,220) and sensitive SERS sensing. (221) This petal-like rough surface is usually induced by the embedding Raman molecules in the insulation layer. So far, several molecules, including oligonucleotides, (222) 4-nitrobenzenethiol (4-NBT), (219) and 4-MBN (223) have been reported to form such shells. But similar thiols, such as 1,4-BDT, 2-naphtalenethiol (NT), biphenyl-4,4-dithiol (BPDT) (i.e., molecules in Figure 11b) do not support the formation of petal-like GERTs. (219) The growth mechanism behind still requires further studies.
In recent years, various GERTs with different core morphologies have been developed, including nanorod GERTs, (214) nanobox GERTs, (224) Au bipyramid GERTs (214) (Figure 11g, ii), and nanotriangle GERTs (185,215) (Figure 11g, iii). Kim et al. reported the dual-gap nanodumbbell GERTs using Au nanorods as the cores, which exhibited the interior gaps not only between core and shell, but also between two semishells (Figure 11g, iv), showing high plasmonic enhancement for label-free Raman assays. (216) Also, GERTs with multiple shells have been proposed, such as nanospherical multishell GERTs with organic molecules embedded, (192) and nanorod multishell GERTs fabricated via galvanic replacement (Figure 11g, v). (217)
NPs composed of Au and Ag are commonly used active substrates, taking advantage of the robust synthesis route of Au NPs and the excellent plasmonic enhancement of Ag material. For example, the Au–Ag nanorod GERTs can be rationally designed to achieve reduced photothermal effect and improved SERS intensity. (225) The Au–Ag petal-core@smooth-shell GERTs, in which petal-like Au NPs serve as the core, providing more hot spots for Raman reporter molecules, and are coated with a Ag shell, further enhancing the brightness (Figure 11g, vi). (218) When using the resonant fluorophores such as IR-780 and IR-1064 as embedded Raman reporters, this kind of resonant GERTs (also denoted as GERRTs) show the single-particle detection capability. (226)
4.2.3. Optical Properties of GERTs
The optical properties of GERTs can be jointly explained by the classical EM theory and the quantum plasmonic theory. Nordlander et al. proposed the plasmonic hybridization model based on EM theory, (227) where the plasmon resonance can be described as the interaction between a nanosphere and a hollow nanoshell. The plasmonic resonance of concentric nanostructures is considered as linear combinations of the plasmons of each part. In this framework, the electromagnetic field enhancement induced by plasmonic coupling inside the GERT nanogap becomes significant as the gap size decreases. However, another important factor affecting GERT signal would be the electron transportation within the gap. When the gap size is reduced to the subnanometer range, electron tunnelling across the junction may occur, (228) and the embedded molecules act as a conductive bridge between the core and the shell and assist in this charge transfer process, analogous to the short circuit. (211) Lin et al. have shown that the optimal size of GERT internal nanogaps is around 1.2–1.6 nm for the maximum SERS enhancement. (211) These unique optical properties make GERTs a good platform to study the charge transport of molecular nanojunctions and its effect on SERS enhancement.
4.3. Orthogonal Raman Reporter Molecules for SERS Nanotags
The overlap of signals from Raman reporter molecules and from endogenous molecules in complex biological systems is a fundamental obstacle, as it affects the accuracy of analysis. It is encouraging to note that mammalian cells exhibit Raman silencing properties in the range of 1800 to 2800 cm–1, which is considered a “biological Raman transparent window”. Most endogenous molecules in this region do not produce Raman scattering signals. This discovery has led to molecules containing alkyne, (229) azide, (230) and metal carbonyl (231) groups as highly attractive Raman reporter molecules. These types of molecules are referred to as “orthogonal molecules”, as they do not interfere with each other or with living organisms in terms of physical and chemical properties. In fact, many ready-made orthogonal molecules have extremely weak signals in the silent region, and many are not ideal Raman reporter molecules in terms of composition or structures. Therefore, it is critical to systematically design and synthesize orthogonal molecules to make SERS nanotags for biolabeling.
So, what characteristics should the ideal orthogonal molecules in SERS nanotags possess? First, orthogonal molecules should be directly bound to the surface of the SERS substrate, as the chemical enhancement effect requires direct contact between the reporter molecules and the substrate, and the electromagnetic field enhancement effect will sharply increase as the distance between the reporter molecules and the SERS substrate decreases. (232) In addition, it is important to avoid the detachment of reporter molecules during subsequent modification processes, which is crucial for the signal intensity and stability of SERS nanotags. (233,234) Therefore, orthogonal molecules should contain thiol or amino groups, which have strong affinity for noble metal elements. (235,236) Second, the characteristic scattering groups of orthogonal molecules (such as alkynes, nitriles, or metal carbonyls) must be connected to molecules with large Raman scattering cross sections to enhance the scattering intensity in the silencing region. (237) Third, the absorption wavelength of orthogonal molecules should be close to the wavelength of excitation light, leading to the appearance of SERRS, which will increase the signal intensity by 2–3 orders of magnitude. (238) Finally, orthogonal molecules should not have too many characteristic peaks in the silent region to avoid spectral overlap between different SERS characteristic peaks in multichannel detection.
Following these empirical rules, Shen et al. designed and synthesized a series of 4-mercaptobenzene derivatives (OPE molecules) with different substitution groups and constructed a set of orthogonal molecules and corresponding SERS nanotags that can be modulated by alkyne scattering, known as the SERS “palette” (Figure 12a). (239) This demonstrated the design and development of orthogonal-molecular-type reporter molecules for SERS nanotags, significantly improving the accuracy and signal-to-noise ratio of SERS nanotags in both multiplex detection and multitarget imaging. (239) The simultaneous and precise detection of heavy metals such as silver and mercury ions in drinking water, organic polluted water, and pigment rich beverages, (243) as well as the one-step detection of biomolecules such as alkaline phosphatase in serum samples, have also achieved good results. (244) Since the Raman readout of orthogonal molecules is unique and specific, and the “Lighting-up” of SERS depends on the aggregation of NPs, Shen et al. also combined magnetic bead immunization, DNA hybridization, adapter recognition, and spectral encoding to obtain more SERS signal outputs without increasing the number of orthogonal molecules, such as click SERS, (240) mixing SERS, (241) and combined SERS (242) (Figure 12b). These signal readout technologies are widely used in multiplex liquid biopsy, bacterial identification, and precise detection or imaging research.
Figure 12
Figure 12. Design and application of orthogonal Raman molecules. (a) Three-color SERS imaging of HeLa cells using SERS nanotags of an alkyne SERS palette; the SERS nanotags were modified with OPE0 (red), OPE1 (green), and OPE2 (blue). Reproduced from ref (239). (b) (i) “Click” SERS for 10-plex synchronous biomarkers detection. Reproduce from ref (240). (ii) “Mixing” SERS for multiplex detection of liver cancer antigens. Reproduce from ref (241). (iii) “Combined” SERS emissions for high-throughput optical labels on microscale objects, such as bacterium. Reproduce from ref (242).
In the biological Raman transparent window, the Raman scattering of carbon materials has also attracted widespread interest, such as the 2D bond characteristic Raman shift of graphene located at ∼2700 cm–1. Based on this, Chen et al. reported a novel graphene shell isolated Au nanocrystal (GIAN) can be used as a SERS tag and demonstrated that GIAN has good chemical stability even in strong acid solution, oxidation solution, and biological environments. (245) Furthermore, it was found that the synthesized GIAN could be suspended at the liquid–liquid interface to adsorb or attach lipids and water-soluble analytes to SERS detection systems, mainly due to the large surface area and unique π–π electrostatic stacking characteristics of graphene. (36,246)
For either organic small molecule or graphene shells, the adsorption, assembly, or bonding processes on the surface of noble metal NPs are tedious, complex, and of poor reproducibility. Liu et al. keenly discovered that Prussian blue, a coordination polymer, can be easily assembled onto the surface of Au NPs. Its rich CN bonds and resonance enhancement in a wide visible wavelength contribute to the strong Raman signal, demonstrating the performance of Prussian blue based SERRS nanotags in high-sensitivity immunoassays and cancer cell imaging. (247) On this basis, Shen et al. modulated the Raman shift of its CN bond through clever ion exchange reactions. The Prussian blue analog on the surface of Au NPs not only protects the stability of the substrate core, but also contributes to high signal-to-noise ratio and high-intensity multicolor SERS signals. (242)
The volume-active SERS (VASERS) technique provides another way to modify the orthogonal molecules onto the NP surface. VASERS integrates a large number of reporter molecules into a polydopamine (PDA) shell with a thickness of several nanometers around metallic NPs via Michael addition, allowing for their controllable arrangement within the 3D zone of the electromagnetic fields of the NPs. (248) This results in a enhancement of the intrinsic signal of the nanotags, making them about 1 order of magnitude brighter than typical self-assembled-monolayer-based SERS nanotags. VASERS strategy enables the use of arbitrary reporter molecules, regardless of their (strong, weak, or even no) affinity to metallic NPs. (249) That is to say, these orthogonal molecules can be devoid of thiol groups and other similar moieties. This implies that there is no need to obtain orthogonal Raman reporters via costly and time-consuming molecular engineering processes. For example, leveraging the advantages of the VASERS technique, SERS nanotags with 32 resolvable Raman colors using commercially available orthogonal molecules were reported, enabling supermultiplexed imaging of 10-panel combined immune checkpoints with high spectral resolution in clinical biopsies of breast cancer. (249)
4.4. NIR-II SERS Nanotags
Over the past decade, near-infrared II (NIR-II, 1000–1700 nm) SERS nanotags have been paid considerable attentions for in vivo spectroscopic detection and bioimaging. (250−252) The NIR-II excitation light generally yields minimal tissue autofluorescence as well as low optical absorption and scattering, which lead to deeper tissue penetration, higher spatial resolution, and higher detection sensitivity in biological tissues than the visible (400–700 nm) and near-infrared I (NIR-I, 700–900 nm) counterparts. (253,254) Similar to conventional SERS nanotags, the most important two components of NIR-II SERS nanotags are the plasmonic substrates and Raman reporters.
NIR-II plasmonic materials play determinant roles in the performance of NIR-II SERS nanotags through the electromagnetic amplification of Raman signals. (255) The properties of plasmonic substrates are closely correlated with their sizes, compositions, shapes, and interparticle interactions. It has been verified that anisotropic noble-metallic nanostructures offer a broader degree of freedom for tuning the plasmon bands from the visible to NIR regions. (256) The plasmonic substrates with resonant LSPR peak at the NIR-II region are usually preferred. For example, He et al. report in their quantitative study that resonant NIR-II nanorods shown an enhancement factor of 4 orders of magnitude, higher than the nonresonant nanorods under 1064 nm excitation (Figure 13a). (257) So far, a multitude of plasmonic Au nanostructures have been endeavored to redshift the plasmonic properties into the NIR-II region, including Au nanorod, (258) Au nanoshells, (259) and hollow Au nanocages. (260) Despite the great SERS enhancement ability, these NIR-II plasmonic Au nanostructures mostly exhibit large overall sizes with at least one dimension of >200 nm, leading to low in vivo targeting delivery and inefficient cell uptake. Li and co-workers have developed a pore engineering strategy to make NIR-II plasmonic nanostructures. (261,262) Specifically, Au@Au–Ag dot-in-cubic nanoframes were designed with a solid spherical Au NP core and the Au–Ag alloy cubic nanoframe (Figure 13b). Such DCFs exhibited remarkable plasmonic properties and near-field enhancement tunable over a spectral range from 700 to 1400 nm through varying the wall hole size and wall thickness while maintaining the small size less than 100 nm in all dimensions, verified by experimental investigations and theoretical analysis. (261) The NIR-II plasmonic nanoframes were further utilized to make NIR-II SERS nanotags, which were demonstrated with remarkable performance for in vivo NIR-II SERS detection and photoacoustic imaging of tumors. Further, a type of porous cubic-AuAg nanoshells (pc-AuAg NSs) with hollow interiors were fabricated by the galvanic replacement reaction and Au/Ag codeposition on the Ag nanocubes as the sacrificial template, followed by oxidative etching with H2O2 (Figure 13c). (262) It could effectively tune the plasmonic properties of pc-AuAg NSs in the NIR range by varying the pore features such as size and pore number could. The pc-AuAg NSs show superior NIR-II plasmonic properties and exceptional NIR-II SERS amplification ability, which is attributed to the high-density hot spots from the nanopores. These NIR-II pc-AuAg NSs were successfully applied for in vivo noninvasive and highly accurate NIR-II SERS visualization of macro- and microtumors (Figure 13c).
Figure 13
Figure 13. Representative NIR-II SERS nanotags. (a) Quantitative enhancement factor study of NIR-II resonant nanorods. Reproduced from ref (257). Copy 2022, American Chemical Society. (b) Design and optical properties of Au@Au–Ag dot-in-cubic nanoframes. They show high SERS intensity to penetrate thick phantoms. Reproduced from ref (261). Copyright 2021, Wiley. (c) NIR-II SERS nanotags made with pc-AuAg NSs and its application for in vivo SERS imaging of tumors. (i) Schematic illustration of the synthetic process of pc-AuAg NSs. (ii) SEM image of Ag and Au of pc-AuAg NSs. (iii) Schematic illustration of the application of NIR-II SERS nanotags for in vivo imaging of tumors in a 4T1 tumor-bearing mouse. Reproduced from ref (262). Copyright 2022, The Authors. (d) The core–shell nanotags with IR-1064 molecules embedded. (i) Schematic illustration of the synthetic process of the core–shell nanotags. (ii) Absorbance spectra of IR-1064 molecules and core–shell nanotags. (iii) They were applied for sentinel lymph node (SLN) detection. Reproduced from ref (263). Copyright 2024, Elsevier.
As for Raman reporters, large Raman scattering cross sections, weak or negligible fluorescence emission and strong binding affinity toward plasmonic substrates are required. (264) The resonant absorption wavelength of Raman reporters matching the excitation laser wavelength leads to additional enhancement of Raman signals with the SERRS effects. (257,263) Deng et al. reported the IR-1048 embedded core–shell SERS nanotags, which showed high brightness (1 pM limit of detection) at NIR-II window; using these nanotags, they realized the intraoperative SERS-guided sentinel lymph node navigation under a clinically safe laser on the preclinical animal models (Figure 13d). (263) Despite the advances using SERRS dyes, these dyes emit strong fluorescence that may compromises SERS detection; similarly, most available Raman reporters for NIR-II SERS nanotags emit weak NIR-II fluorescence. The invention of nonfluorescent NIR-II Raman reporters with large Raman scattering cross sections are thus critical. For example, Li et al. reported a nickel dithiolene complex as a NIR-II resonance Raman reporter, with intense absorption (absorption coefficient ε = 9.58 × 104 m–1 cm–1) at around 1000 nm, fluorescence-free features, and high affinity to Au NPs. (265) When adsorbed onto Au nanorods, these dyes form bright and stable SERRS nanotags amenable to high-contrast and highly photostable lymph node imaging as well as in vivo tumor detection.
Despite the great advances of NIR-II SERS nanotag-based biomedical applications, future studies should focus on the following aspects: (1) NIR-II plasmonic nanostructures should be explored to further boost the SERS amplification ability for biomedical applications. (2) The NIR-II SERS measurements have been performed using expensive and relatively large Raman systems, which greatly limiting the clinical translation of NIR-II SERS nanotags. (3) The biocompatibility and biosafety of NIR-II SERS nanotags should be investigated in detail and be ensured for practical applications in humans (More discussions can be found in section 9).
4.5. Surface Functionalization via Biomimetic Cell Membranes
The stability of SERS nanotags in aqueous solutions and their long-term colloidal stability in a biological milieu is of unmet importance for in vitro and in vivo applications. This stability of SERS nanotags is primarily dictated by the Raman reporter molecules adsorbed on the plasmonic Au NP surface. Initial efforts in the SERS field employed chemical modulation strategies that conjugated ethylene glycol linkers on the terminus of a representative Raman reporter molecule, mercaptobenzoic acid. (266) This culminated in improving their stability and aqueous solubility owing to the hydrophilic nature of ethylene glycol and further resulted in a reduction of nonspecific binding. Further research showcased that trimethylene glycol units allowed controlled bioconjugation and increased steric accessibility. (267) Stabilizing SERS nanotags in biological fluids is crucial without compromising their signal due to aggregation in high-ionic-strength media and as such, various polymers have been used as protective layers or “coatings” to stabilize SERS-encoded particles and prevent Raman reporter release or nonspecific protein adsorption. PEG is exceptionally versatile due to its biocompatibility, enabling extended blood circulation and allowing controlled polymerization to incorporate specific end groups like thiols for anchoring onto Au NPs. However, in recent years, PEG-specific immune responses have increasingly hindered their in vivo applications. (268) Another approach is encapsulating Au NPs within cross-linked polymers, such as poly(N-isopropylacrylamide) (pNIPAM). The porous pNIPAM coating permits Raman reporter incorporation and facilitates antibody conjugation via outer polyelectrolyte coatings. (269,270) Amphiphilic diblock copolymers like polystyrene-block-poly(acrylic acid), and dodecylamine-modified polyisobutylene-alt-maleic anhydride (PMA) also stabilize SERS nanotags through uniform coatings. (271) Phospholipids provide biologically compatible coatings for Au NPs, enhancing versatility. (272−274) High-molecular-weight proteins like bovine serum albumin (BSA) stabilize encoded Au NPs by preventing aggregation and desorption of Raman-active molecules through electrostatic mechanisms and thiol binding. (275) Similarly, antibodies can be used as stabilizing agents, allowing one-step bioconjugation of the SERS nanotags. (276)
The last step in creating SERS nanotags involves bioconjugation with a tumor-targeting moiety, providing the SERS nanotags with high specificity toward cancer. This bioconjugation process for SERS nanotags uses a functional coating as a stabilizing layer, typically carboxyl groups or primary amines. These groups facilitate AuNP bioconjugation through amide bond formation via carbodiimide activation. Several polymer chemistry modification strategies like Michael addition, click chemistry, or Diels–Alder reaction have been used to provide AuNP functionalization with biological molecules. Sulfhydryl-containing biomolecules can be conjugated to the BSA layer by forming S–S bonds. Bioconjugation of biopolymer-stabilized Au NPs relies on terminal amine and carboxyl groups using EDC/NHS chemistry. For instance, Knudsen et al. stabilized SERS nanotags with BSA and glutaraldehyde, creating a cross-linked organic encapsulation. (277) This process removes most surface amino groups from BSA, resulting in SERS nanotags with a net negative charge from carboxylic acid groups. For silica-encapsulated SERS nanotags, silanes with amino or thiol groups (e.g., APTMS and MPTMS) are used for bioconjugation. (278) Heterobifunctional cross-linkers, such as those with NHS ester and succinimide ends, couple amino- or thiol-functionalized SERS nanotags to target-specific ligands like antibodies. (279) Besides, biotin-modified antibodies can be bound to the streptavidin-labeled nanotags using the strong affinity between biotin and streptavidin.
An innovative approach using functional cell membrane coatings derived from erythrocytes (red blood cells) as a potential coating was reported by Nie and Srivastava et al. on SERS nanotags of various shapes and sizes (Figure 14). (280) These biomimetic SERS nanotags demonstrated superior enhanced stability, SERS signal amplification, and targeted tumor cell recognition. The membrane coating brought long-term colloidal stability for nanotags and robust protection against adverse conditions such as freezing, lyophilization, high buffer concentrations, and heating. Remarkably, the SERS signal stability profile remained consistent across all these conditions. Furthermore, the study revealed that biomimetic red blood cell membrane (RBCm) coating on dye-tagged Au NPs significantly enhanced SERS, culminating in a 5-fold increase in SERS intensity compared to PEG-coated- dye-tagged Au NPs. This enhancement was confirmed independent of hotspot effects, as consistent absorbance and size distribution data indicated. Additional experiments underscored the importance of tight RBCm wrapping for maximum SERS enhancement. Simple mixing of AuNP-dye with RBCm fragments yielded only a 3-fold increase, whereas bath sonication improved membrane packing, achieving 5-fold enhancement. The observed SERS enhancement is attributed to the electromagnetic enhancement mechanism, where transitioning from a dielectric medium from a polar water environment to a nonpolar lipid bilayer significantly reduces electron damping and amplifies the electromagnetic field. RBCm were functionalized with tumor-targeting peptides to target tumor cells and coated onto dye-tagged AuNPs. Initially, for optimization, a lipid-insertion strategy was adopted using a lipid-tethered tumor-targeting ligand (DSPE-PEG-cRGD) was functionalized RBCm which were subsequently coated onto dye-tagged Au NPs. cRGD peptides target integrin receptors, particularly ανβ3 integrins, which are upregulated in specific cancer cells. The targeting efficiency was evaluated using two representative cancer cell lines: MDA-MB231 (high ανβ3 expression) and PANC-1 (low ανβ3 expression). Strong binding and SERS signals were observed in MDA-MB231 cells, while minimal signals were detected in PANC-1 cells, confirming selective targeting ability. Flow cytometry data further validated these findings. This study demonstrates the potential of cell-membrane-coated SERS nanotags with easy tumor-targeting ligand modifications to boost detection sensitivity toward metastatic tumor cells compared to nonmetastatic tumor cells, offering a promising avenue for advanced biomedical applications. Future researches are investigating into the use of tumor cell-derived membrane coatings for imparting homologous tumor targeting of SERS nanotags, potentially obviating the requirement for supplementary targeting peptides.
Figure 14
Figure 14. RBCm coated SERS NPs. (a) Schematic diagram showing preparation of RBCm vesicles and successful coating on anisotropic Au NPs, leading to RBCM-coated AuNP-RBCm with enhanced dispersibility and biofunctionalization properties. Physicochemical characterization of anisotropic RBCM-coated AuNPs. Negative-stained transmission electron micrographs of (b) bare AuNP1, (c) RBCm-coated AuNP1, (e) bare AuNP2, (f) RBCm-coated AuNP2, (h) bare AuNP3, and (i) RBCm-coated AuNP3. The membrane coating in (c, f, i) are highlighted with white lines. (d, g, j) UV–vis absorbance spectra of AuNPs and AuNP-RBCMs, with the inset boxes zoomed. The inset shows the intrinsic plasmonic absorbance peak shift for different anisotropic AuNPs upon RBCM coating. Reproduced from ref (280). Copyright 2022, American Chemical Society.
Srivastava and Nie et al. further advanced cell-membrane coating technology by developing dual-modality plasmonic nanostructures using colloidal Au nanostars. (281) These nanostructures aimed to overcome the limitations of spectroscopic techniques in image-guided surgery, specifically in detecting hidden or buried tumors within healthy tissues. Coated with RBCm, these biomimetic plasmonic nanostructures enhance both SERS and photoacoustic detection of tumor phantoms within animal tissues. Compared to PEG-coated Au nanostars, the biomimetic coatings significantly reduced protein adsorption in human plasma, minimized uptake by murine macrophages, and improved cellular uptake in tumor cells, all while maintaining robust SERS and photoacoustic signals. The biomimetic RBCm coating comprises of abundantly expressed CD47 proteins on the surface, function as “marker of self” receptors. By binding to signal-regulatory protein alpha (SIRPα) receptors on macrophages, they inhibit phagocytosis of RBCs. Consequently, RBCm-coated nanotags leverage these CD47 proteins to evade immune clearance, resulting in prolonged circulation and enhanced tumor-targeted delivery. (268) Based on this mechanism, it is hypothesized that this is the plausible reason why AuNS-RBCm exhibited reduced macrophage uptake in murine macrophages compared to uncoated PEGylated AuNSs, which lack CD47 receptor expression. RAW 264.7 were taken as the in vitro model of reticuloendothelial system clearance for this study. Moreover, since RBCm are derived from the natural cells of mice and are free from synthetic or immunogenic components, they exhibit inherent biocompatibility. This property has been demonstrated not only with Au NPs but also with nanoparticles, including conjugated polymer nanoparticles. (282,283) Furthermore, by incorporating tumor-targeting peptides like cyclic RGD, these NPs can precisely target ανβ3-integrin receptors on metastatic cancer cells, facilitating accurate tracking through SERS and photoacoustic imaging. To simulate in vivo buried tumor lesions, they demonstrated these nanotags’ effectiveness in image-guided resections of tumor-mimicking phantoms, simulating metastatic tumor cells buried under up to 6 mm of skin and fat tissues. Photoacoustic imaging accurately located the tumors, while SERS signals enabled their identification and differentiation. This study underscores the potential of biomimetic dual-modality NPs for intraoperative cancer detection and resection, offering superior signal quality and biological stability.
5. Emerging Instrumentation in Biomedical Applications
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5.1. Optical Tweezers for Single-Particle and Single-Cell SERS
As a convenient approach to suppress Brownian motion and control the position of micro- and nanoscale objects suspended in solution, optical trapping techniques have been integrated with microfluidic systems to improve the efficiency and reproducibility of SERS measurements for various biomedical applications. Optical tweezers, also known as optical traps, utilize highly focused laser beams to manipulate objects, such as cells, microparticles, NPs, molecules, and atoms, with fine temporal and spatial resolution. The basic principle relies on the momentum of light, where the focused laser beam creates a gradient in light intensity that interacts with the object through absorption, reflection, refraction, or scattering, exerting forces to attract it toward the focus. By adjusting the position of the focused laser beam, researchers can move the trapped object without physical contact. This capability enables dynamic and precise positioning of target analytes near SERS-active substrates, thereby facilitating signal enhancement and acquisition.
For microscale object manipulation, McNay et al. designed a partially Ag-coated silica microparticle as an optically trappable and microscopically visible SERS mobile probe, (289) which was refined by Balint et al. for spatial SERS scanning detections of cell membranes. (290) As shown in Figure 15a, Stetciura et al. decorated silica microparticles with metal NPs as SERS-active satellites and guided to specific compartments to monitor intracellular compositions for single-cell analysis. (284) For nanoscale object manipulation, Svedberg et al. assembled two Ag NPs into a dimer to form a dynamic hotspot with an apparent SERS intensity increase. (291) Tong et al. (292) and Messina et al. (285) harnessed optical aggregation of multiple metal NPs, generating numerous interparticle hotspots and boosting the SERS signal of adsorbed analytes, as illustrated in Figure 15b. (285) Coupled with plasmonic heating, Fazio et al. aggregated Au nanorods to detect nonresonant proteins in the μg/mL range. (293) Furthermore, Hong et al. exploited an additional plasmonic trapping effect at a gap within Au nanobowtie structures to gradually deposit the aggregation of Au NPs and enhance the detection sensitivity for Rhodamine 6G to 100 pM, as presented in Figure 15c. (286) These studies showcase the use of spatiotemporal control in hotspot generation and movement for the sensitive SERS detection of analytes directly from native solutions, eliminating the need for additional capping agents such as salts or acids.
Figure 15
Figure 15. Illustration of optical tweezers-coupled SERS platforms. (a) SERS-active satellite transport by laser tweezers to the surface of a cell. (b) Raman tweezing. (c) Autoenhanced Raman spectroscopy and time-dependent Raman signals after laser exposure. (d) Optical tweezers-coupled Raman spectroscopic platform. SERS spectra and intensity as a function of the distance between two Ag NP-coated beads from beads approaching to beads separating. (e) Optical plasmonic tweezer-coupled SERS platform. SERS spectra recorded at a Ag NP-coated bead dimer with the switching of trapping laser between on (red) and off (black) states. Adapted with permission from refs (284−288). Copyrights 2015, Royal Society of Chemistry; 2011, American Chemical Society; 2016, American Chemical Society; 2021, The Author(s); and 2023, The Authors, respectively.
By combining micro- and nanoscale object manipulation, Dai et al. brought two Ag NP-coated silica microbeads together to create a dynamic hotspot, achieving tunable and reproducible SERS enhancements with single-molecule sensitivity. (287) Figure 15d illustrates this controllable hotspot and demonstrates the emergence, enhancement, and disappearance of the SERS signal from 1% ethanol solution as the two beads were approached and then separated. (287) To prevent potential photothermal damage, the distance between the two beads was adjusted in real-time, preserving protein native states and enabling their accurate structural characterizations during SERS measurements. (287) Moreover, precise spatiotemporal control over the hotspot formation with a finite detection volume could reduce ensemble averaging to directly characterize the structures of low-populated alpha-synuclein species among its predominantly unstructured monomers at 1 μM physiological concentration. (287) Recently, Fu et al. constructed a plasmonic junction between two Ag NP-coated silica microbeads to exert additional optical plasmonic trapping to hold a freely diffusing Ag NP and form a SERS-active nanocavity, as depicted in Figure 15e. (288) Since both optical plasmonic trapping and SERS techniques are surface-sensitive relying on the metallic substrate within a nanometer range, this integration could overcome the optical diffraction limit to precisely define the location of hotspot and reduce the SERS active-detection volume for huge SERS enhancements. By toggling the trapping laser on and off, the Ag NP was alternately trapped and released at the plasmonic junction, capturing target analytes in the confined detection volume for efficient and continues high-throughput single-molecule SERS measurements. (288) It could acquire a statistically significant number of molecular SERS snapshots of human islet amyloid polypeptide among a heterogeneous mixture, comparable to molecular dynamics simulations, providing the unique single-molecule level structural details and population of specific species to reveal the mechanism of pH-regulated amyloid aggregation. (288) These studies present an optically controllable strategy for single-molecule SERS detection by simultaneously reducing detection volume, enhancing molecular signal, and improving measurement efficiency, which overcomes ensemble averaging and enables investigation of complex biological systems at the single-molecule level.
Beyond controlling SERS substrates, optical tweezers further facilitate direct manipulation of diverse biological samples. For instance, Lu et al. selectively isolated a single microbial cell from a mixed population (294) and Shang et al. captured individual lactic acid bacteria along with Ag NPs, (295) enhancing the stability of SERS measurements for rapid identification and classification of microbes at a single-cell level. In addition, Kitahama et al. verified that single molecules could be optically trapped via plasmon resonance at the junction of Ag nanoaggregates, yielding blinking single-molecule SERS signatures. (296) Oyamada et al. reported in situ electrochemical SERS detection of individual small size molecules upon plasmonic optical trapping at the gap of a single metal nanodimer immersed in an electrolyte solution. (297) However, a potential limitation of plasmonic optical trapping lies in the heating effect inherent to metallic plasmonic materials upon illumination, which may compromise the stability of trapped biomolecules and affect the outcomes of SERS analysis. For example, Yang et al. observed conformational changes in a single protein at a plasmonic gold nanopore, noting that intense heating could lead to protein denaturation. (298) Besides, this technique faces challenges from additional thermal phenomena, such as thermophoresis and thermo-osmosis, which may further perturb table SERS measurements. As an alternative trapping technique, all-dielectric tweezers, particularly those employing anapole modes, offer reduced heating, greater stability, and enhanced biocompatibility for the trapping of single and multiple objects, which holds promise to improve the SERS signal stability from trapped biological samples. This approach was proposed theoretically by Hernández-Sarria et al. and then validated through experimental studies on vesicle trapping by Hong et al. and Conteduca et al., respectively. (299−302) These advances demonstrate the unique capability to directly manipulate biological samples through optical trapping techniques, introducing new dimensions for their preparative treatment and spectroscopic detection at the smallest scales and deepening the scope of biomedical investigation. Moreover, the dual functionality for substrate and sample manipulations could optimize spatiotemporal resolution and empower explicit control over molecular position, orientation, and interface interactions near SERS-active substrates at nanoscale precision, which would facilitate the characterization of structures and conformational dynamics of complex biological macromolecules. Further developments in the optical tweezers-coupled SERS platform would enhance its analytical potential for controlling, detecting, and elucidating intricate biological processes, which holds the promise to evolve into a versatile tool and inspire innovative applications for biomedical research in the future.
5.2. Plasmonic Nanopore Systems for Single-Molecule SERS Sensing I: Principles and Instrumentation
Single-molecule SERS represents the frontier of SERS sensing, (303) aiming to detect and analyze individual molecules, crucial for studying chemical reactions and complex biological interactions at the single-molecule level. Achieving single-molecule SERS requires creating “hotspots” that allow for the localized enhancement of Raman signals for single molecules, but challenges such as reproducible hotspot creation, precise molecular positioning, and signal differentiation from noise remain significant. Various strategies, including the use of nanogaps, nanocavities, and nanotips, (304−308) have been developed to achieve single-molecule SERS. However, these methods often rely on the random capture of molecules into plasmonic hotspots, limiting their high-throughput capabilities. Nanopore analysis, a technique used to study and characterize individual molecules by detecting changes in ionic current as they translocate through a nanoscale pore in a solid membrane, offers a promising alternative. Plasmonic nanopores integrate the traditional nanopore features with plasmonic effects by utilizing noble metals like Au or Ag to generate “hotspots” with enhanced electromagnetic fields within the nanopore. The external electric field in nanopores facilitates the sequential capture, analysis, and release of single molecules in these hotspots. “ This allows for simultaneous measurement of electric signals and Raman signals from a single molecule (Figure 16a).
Figure 16
Figure 16. Plasmonic nanopores and related applications. (a) Plasmonic nanopore-based single molecule electrical and optical measurement. Reproduced from ref (309). (b) Integrated system for the optical and electrical detection of nanopore analysis. Reproduced from ref (309). (c) In situ electrochemical modification of metallic nanopore. Reproduced from ref (309). (d) Schematic of a solid-state nanopore with an integrated bowtie-antenna structure for DNA translocation experiments. Reproduced from refs (310and311). (e) Schematic of the bowl-shaped plasmonic nanopore system for Raman detection of single DNA molecules. Reproduced from ref (316). (f) Schematic diagram for the dynamic SM-SERS detection by plasmonic nanopipettes. Reproduced from refs (318and319).
The design and implementation of nanopore systems for single-molecule SERS hinge on two key components: the measurement system and plasmonic nanopore fabrication. The measurement system for nanopore-based single-molecule SERS typically includes a laser source for excitation, a Raman spectrometer for signal detection, an amplifier for ionic current acquisition and a control module for the synchronization of electrical and optical signals (Figure 16b). In previous studies, advanced systems for single-molecule analysis have been reported. For example, Long and co-workers developed a unified optical and electrochemical synchronous measurement platform for protein nanopore, solid-state nanopore, and glass capillary nanopore. (309) In addition, an in situ chemical reduction method for constructing plasmonic nanopores was proposed and used to detect the SERS signal of DNA (Figure 16c). Constructing a plasmonic nanopore with a high enhancement factor is a challenging task. A classical plasmonic nanostructure for nanopore sequencing is reported by Belkin et al. in 2015. (310) The work proved theoretically that nanopore confined plasmonic field formed by paired nanoantenna can ensure nanometer resolution to decode the DNA sequence during the translocation through a nanopore by means of SERS. Xin et al. developed a plasmonic antenna with a sub-3 nm nanogap integrated into a SiNx nanopore, which efficiently captured single DNA molecules into plasmonic hotspots for single-molecule analysis (Figure 16d). (311,312) There are many other plasmonic nanopore have been reported. (313−315) Recently, a plasmonic bowl-shaped nanopore was reported by Zhao et al., (316) that capable of direct Raman detection of single λ-DNA molecules. The plasmonic hot spot has a size of less than 3 nm along the direction of translocation, enabling the revelavation of DNA submolecular segments composed of only 7 bases (Figure 16e). Moreover, plasmonic nanopores fabricated by assembling Ag nanotriangle, Au nanoplates, or Au nanolayer at the orifice of the nanopipets were reported (Figure 16f), enabling the detection of DNA bases, protein Segments and oxygenated/deoxygenated states of single hemoglobin during direct translocation by SERS. (317−319)
In general, these studies collectively demonstrate that the potential of plasmonic nanopores in achieving single-molecule SERS. The plasmonic effects give the nanopore the ability to enhance and measure single-molecule Raman signals, while the nanopore architecture facilitates the easy capture of single molecules into “hotspots”. This integration simplifies single-molecule SERS techniques and allows for the simultaneous acquisition of optical and electrical multimodal signals, thus advancing the precise measurement and characterization of single molecules. Despite the remarkable progress and potential of plasmonic nanopores for single-molecule SERS, several challenges and limitations must be addressed to fully realize their capabilities for precise single-molecule analysis. Producing high-quality plasmonic nanopores necessitates precision nanofabrication techniques, limiting their wide application. The enhancement of the Plasmonic nanopore depends on the strength of the local electromagnetic field, which is limited to a small area around the nanopore. As a result, only molecules close to the nanopore can be accurately detected, while those that are farther away have much weaker signals. Thus, developing nanopores with a high enhancement factor and a low-cost is critical. Additionally, optimizing and extending the duration of single-molecule within the hotspots of plasmonic nanopore to obtain high-resolution ionic current signal and spectral signals is also an important factor in enhancing the accuracy of single-molecule measurements.
5.3. Plasmonic Nanopore Systems for Single-Molecule SERS Sensing II: Biomolecule Sequencing
Single-molecule sequencing for detecting the order of the basic units of an individual biomolecule, such as nucleobases in DNA or amino acids in proteins, is playing significant role in all biomedical fields from mechanical study to clinical diagnosis. (320) Single-molecule sequencing is particularly important for proteins due to the fact that proteins cannot be amplified as polymerase chain reaction (PCR) does for DNAs. Because most biomolecules exhibit folded conformations in liquid, they usually need to be unfolded in nanopore sequencing (Figure 17a). For example, single-molecule protein sequencing needs to first unfold the 3D structure of the protein into a primary structure, identify the amino acids in the protein chain and then determine the order of the amino acids. When SERS-active plasmonic nanopores are used in single-molecule sequencing, the molecule would be unfolded by being driven electrically through the nanopore and then detected in the plasmonic hot spot by SERS (Figure 17b). Because single-molecule DNA sequencers have been commercialized, DNA is simpler than proteins in molecule structure and surface charges, development of single-molecule protein sequencing technologies usually use DNAs for benchmarking. However, identification of 20 proteogenic amino acids in proteins is a longstanding challenge in single-molecule protein sequencing by either fluorescence methods or biological nanopore resistive pulse sensors. (321) SERS-active plasmonic nanopores start to play a role in single-molecule sequencing because they can enhance and detect the intrinsic fingerprint Raman spectra of the 4 nucleobases and the 20 amino acids with single-molecule sensitivity. (322−324)
Figure 17
Figure 17. Plasmonic nanopore for biomolecule sequencing. (a) Unfolding a protein for plasmonic nanopore sequencing. (b) The schematic of the plasmonic bowl-shaped nanopore system in which the DNA (green line) would be first uncoiled by the hydrogel (blue circles) and then passed through the hot spot. (c) The cross-sectional distribution of the surface charge of the bowl-shaped nanopore under electric bias. (d) The simulated EO flow distribution in the bowl-shaped nanopore and path of the DNA movement under electric bias (white line). (e) Schematic of the particle-in-pore sensor that could trap single Au NP for tens of seconds. (f) The molecule would be adsorbed on the NP before trapping. (g) The generated gap-mode hot spot with size of 1–3 amino acids. (h) The time series of collected single-molecule SERS spectra of the vasopressin peptide in the electro-plasmonic nanopore. (i, j, k) Single-molecule SERS spectra at different times from (h) that represent the neighboring amino acids. Panels (b–d) are adapted with permission from ref (316). Copyright 2023, American Chemical Society, and panels (e–k) are adapted with permission from ref (283). Copyright 2022, American Chemical Society.
Therefore, single-molecule SERS sequencing needs to detect an individual biomolecule during its movement through the plasmonic nanopores. Even though the plasmonic hot spot is sensitive enough, it remains an issue how to unfold the molecule and locate it in the hotspot in the plasmonic nanopores controllably to collect enough SERS signals for sequence reconstruction. For a successful sequence reconstruction from the single-molecule SERS data, the molecule must always pass through one hot spot in a linear way. Otherwise, if the molecule passes through 2 or more hotspots, single-molecule SERS signals from different segments of the molecules would be mixed and difficult to be analyzed. Accordingly, Zhao et al. used focused ion beam (FIB) to fabricate an Au bowl-shaped nanopore of 20 nm diameter on a silicon nitride (Si3N4) membrane that could generate 2 strong hotspots for SERS sequencing (Figure 17b) in contrast with conventional cylindrical plasmonic nanopores with 4 hotspots. (316) The surface plasmon resonance of the bowl structure could focus the excitation light into the nanopore edge such that the intensity of the hotspot would increase with decreasing pore diameter. Moreover, the Au bowl-shaped nanopore had the floating surface charges (Figure 17c) that generated the electro-osmotic (EO) sheath flow at the pore edge under positive electric bias. As shown in Figure 17d, the electro-osmotic sheath flow together with the electrophoretic (EP) force unfolded the DNA and directed it to the edge of the bowl-shaped nanopore where one of the 2 hotspots was exactly located. Such single-molecule manipulation of the linear λ-DNA movement through the hot spot was confirmed by the collected single-molecule SERS signals of the DNA bases. The extracted sequences based on the single-molecule SERS spectra were agreed with the segments of the λ-DNA sequence in the database. (316)
For SERS sequencing of single-molecule proteins, Zhou et al. fabricated a sub-10 nm conical plasmonic nanopore by electrochemically coating a glass nanopipette with Au layer to investigate the sequence of single cytochrome c protein under electric bias (Figure 17f). (319) When the electric bias was increased to −700 mV, the single-molecule SERS spectra indicated that the cytochrome c was unfolded and passed through the nanopore in a sequential multistep manner. Based on a single-molecule SERS database of different segments of the cytochrome c, the authors were able to reconstruct the segment sequence of the protein. To increase the SERS sequencing resolution, Li et al. used the conical plasmonic nanopore to detect single-molecule peptides with single-amino acid variations by both resistive pulses and SERS. (325) By collecting large amount of single-molecule SERS spectra of the peptides, they developed a statistical data analysis method the extract the single-molecule SERS features of the peptides and identify the single-amino acid substitution. To increase the SERS sequencing throughput, Iarossi et al. combined nanosphere lithography and focused ion beam to fabricate high-density plasmonic nanopore array with 10 nm pore diameters and 100 pores per square micron on a Si3N4 membrane. (326) They demonstrated high capture rate of the DNAs and achieve single-molecule SERS detection of DNA solution of a low concentration of 50 fM.
In the above plasmonic nanopore sequencing, the biomolecules passed through the nanopores so fast that only different segments of the molecules were observed. As an alternative, Huang et al. developed an electro-plasmonic trapping method, Particle-in-Pore sensor, that enabled detection of neighboring amino acids in a single-molecule peptide (Figure 17e, g). (323,327) The peptide was first adsorbed on a Au NP (Figure 17f) that would then be driven into a Au plasmonic nanopore by electric bias. Because the nanopore had similar surface charge as those on the Au NP, the electro-osmotic force and electrophoretic force on the NP counterbalanced each other. Meanwhile, the plasmonic force of the nanopore dragged the NP to the pore wall to generate a strong and localized single gap-mode hotspot with the size of 1–3 amino acids that could detect both aromatic and nonaromatic amino acids (Figure 17g, k). (327) The combined effect of these forces allowed the NP stayed in the nanopore, and also kept the molecule in the hot spot, for tens of seconds (Figure 17h). Such a long time allowed single-molecule SERS observation of the diffusion of a single vasopressin peptide across the hot spot by signals of its neighboring amino acids from Pro (Figure 17k), Arg-Pro (Figure 17j) to Arg-Pro-Cys (Figure 17i). The authors envisioned that the SERS feature of the neighboring amino acids could be used to sequence single-molecule proteins with single- amino acid resolution. While driving the molecule through the hotspot by electric bias controlled the molecule movement direction with less sequencing resolution, molecular diffusion in the hot spot provided higher resolution but could not control the molecule movement. We expect further development of the plasmonic nanopores may include automatic control to provide both high resolution and movement control for single-molecule SERS sequencing.
5.4. Wearable SERS-Based Sensors
Detection and quantification of biochemicals in body fluids are essential for early disease diagnosis, personalized health monitoring, and precision medicine. The analysis of body fluids, such as blood and urine, for clinical diagnosis takes several days from sample collection to central lab testing, which cannot provide real-time information for timely clinical intervention. (328) Wearable sensors show the potential to provide continuous, real-time quantification of molecular targets noninvasively. The peripheral fluids that can be noninvasively accessed by wearable devices include sweat, saliva, and tears. Among these, sweat is attractive due to several advantages, including reliable sample collection methods, continuous accessibility, and workable sample volume. (329,330) Wearable sweat sensors have shown the capability of analyzing various molecular targets, including electrolytes, metabolites, hormones, drugs, and proteins. (330−332) Recently, wearable SERS sensors have been developed to monitor many of these molecular targets by leveraging the advantages of SERS, including high sensitivity, specificity, and multiplex capability. In addition to these common factors of SERS sensor performance, important design considerations of wearable devices include sample collection efficiency, device stretchability, stability, and durability to enable their reliable in vivo performance. Here, we highlight recent SERS-based sweat sensors, important design considerations for wearable devices, and challenges and opportunities to translate these sensors into clinical and point-of-care applications.
Plasmonic nanomaterials in wearable SERS sensors are mainly made of Ag and Au, owing to high SERS enhancement. Ag nanostructures offer higher SERS enhancement than Au counterparts, although Ag has limited chemical and environmental stability, resulting in decreased SERS performance over time. (333,334) Top-down and bottom-up approaches have been utilized to fabricate and synthesize these materials with well-defined dimensions and shapes, including nanosphere, (335) nanorod, (336) nanocube, (337) nanowire, (338) nanofiber, (339) and nanomesh (340) (Figure 18a–h). In comparison, a top-down approach is relatively high-cost, time-consuming, and less efficient at producing large quantities of nanostructures compared to a bottom-up approach. Here we introduce SERS substrates in sweat sensors fabricated with both approaches, their sensing performances for sweat analysis, and flexibility and stretchability for wearable applications below. Table 2 summarizes plasmonic nanostructures, surface functionalization, substrates used for detecting and quantifying various analytes in sweat, the sensitivity and continuous monitoring capability, and the stretchability and flexibility of the SERS substrates and wearable devices.
Figure 18
Figure 18. Wearable SERS-based sensing devices. SEM images of (a) Ag nanomushroom array, (b) Au nanosphere cone array, (c) Au-coated electrospun thermoplastic polyurethane fibers, and (d) Au nanomesh. (e) TEM image of Ag nanocube superlattice. Scale bar: 50 nm. SEM images of (f) plasmonic nanovoids array (scale bars: 1 μm (top) and 200 nm (bottom)), (g) Au nanorods on chromatography paper, and (h) Au nanospheres on alkalized V2C MXene membrane. Inset: optical image of the Au NP-modified MXene membrane. (i) Optical image of a SERS sensor within PDMS microfluidics and (j) corresponding continuous SERS measurements of lactate with varying concentrations. (k) Optical image of SERS sensors distributed along a paper microfluidic channel and (l) continuous SERS measurements of uric acid with varying concentrations. (m) Optical image of a portable Raman spectrometer used in on-body measurements. (n) Optical image of a multiplex sensor array with a sweat extraction system. Scale bar: 1 cm. (a, i, j) Reproduced from ref (341). Open access. (b) Reproduced with permission from ref (335). Copyright ACS. (c) Reproduced with permission from ref (339). Copyright ACS. (d) Reproduced from ref (340). (e, n) Reproduced from ref (337). Open access. (f) Reproduced with permission from ref (342). Copyright Wiley. (g, k, l, m) Reproduced from ref (336). Open access. (h) Reproduced with permission from ref (345). Copyright ACS.
Table 2. List of Wearable SERS Sensors for Sweat Analysisa
| Plasmonic materials | Molecular targets | Surface functionalization | Substrates for plasmonic materials | Sensitivity | Continuous monitoring | SERS substrate and device flexibility | SERS substrate and device stretchability |
|---|---|---|---|---|---|---|---|
| Au nanosphere cone array (335) | Acetaminophen | No | Silicon nanocone array | 0.13–100 μM | Yes | Substrate-No | Substrate-No |
| Device-Yes | Device-No | ||||||
| Au/TPU Nanofibers (339) | pH | 4-MBA or 4-Mpy | Electrospun TPU Nanofibers | pH 4–8 | NA | Substrate-Yes | Substrate-Yes |
| Device-Yes | Device-Yes | ||||||
| Au nanomesh (340) | Urea | No | PVA fiber nanomesh | 1–100 mM | NA | Substrate-Yes | Substrate-Yes |
| Ascorbic acid | 1–1000 nM | Device-Yes | Device-Yes | ||||
| Au nanorods (336) | Uric acid | No | Chromatography paper | 1 −100 μM | Yes | Substrate-Yes | Substrate-No |
| Device-Yes | Device-Yes | ||||||
| Au nanosphere (345) | Nicotine, methotrexate, nikethamide, 6-acetylmorphine | No | Alkaline-treated MXene | 10 nM–1 mM | NA | Substrate-Yes | Substrate- NA |
| Device-Yes | Device- NA | ||||||
| Ag nanomushroom array (341) | Urea | No | Silicon nanopillar array | 0.1–1000 mM | Yes | Substrate-No | Substrate-No |
| Lactate | No | 0.01–100 mM | Device-Yes | Device- No | |||
| pH | 4-MBA | pH 4–8 | |||||
| Ag nanocube superlattice (337) | Nicotine | No | PMMA | 100 nM–10 μM | Yes | Substrate-Yes | Substrate-No |
| pH | 4-Mpy | pH 4.0–6.5 | Device-Yes | Device-Yes | |||
| Ag nanosphere array (342) | Dopamine | 3, 3′dithiodipropionic acid di(Nhydroxysuccinimidyl ester) | Au/SiO2 coated polystyrene microarray | 1 pM–1 nM | NA | Substrate-No | Substrate-No |
| H2S | 4acetamidobenzenesulfonyl azide | 1 ppb–100 ppm | Device-Yes | Device-Yes | |||
| Ag nano snow flakes (361) | Creatinine | No | Hydrophobic filter paper | 12–40 ng | NA | NA | NA |
| Cortisol | No | 16–400 pg | |||||
| Ag nanoparticles (366) | Urea | No | Sulfonated cellulose nanofiber | 0.1–1000 mM; LLOD: 63.1 μM | NA | Substrate-Yes | Substrate-Yes |
| Uric acid | No | 0.005–1 mM; LLOD: 3.98 μM | Device-Yes | Device-Yes | |||
| pH | 4-MBA | pH 4.0–8.0 | |||||
| Ag nanowire (338) | 2-fluoromethamphetamine | No | Silk fibroin protein film | 50 ng/cm2–2.5 μg/cm2 | NA | Substrate-Yes | Substrate-NA |
| Device-Yes | Device- NA |
a
NA denotes not available.
The top-down approach for fabricating a wearable SERS substrate involves the physical deposition of Au or Ag nanometer-thin films onto a nanoscale scaffold. Figure 18a shows the Ag nanomushroom array fabricated on a silicon (Si) wafer. (341) The fabrication steps include self-assembly of a monolayer of polystyrene (PS) nanospheres with a diameter of 120 nm, reactive ion etching to form well-aligned Si nanopillars, residual PS removal, and sputter deposition of a thin Ag layer. The densely distributed gaps of less than 10 nm between nanomushrooms provide strong SERS enhancement of analytes. The SERS substrates provided an enhancement factor of 1.5 × 106 using rhodamine6g (R6G) as a model analyte. These SERS substrates were cut into circular pieces with a diameter of 3.9 mm to assemble into a wearable device. The demonstrated capability with the SERS substrates includes the quantification of urea in the concentration range from 0.1 to 1000 mM, lactate from 0.01 to 100 mM, and pH 4 to pH 8. The continuous monitoring of time-varying concentrations of these analytes was also demonstrated and validated with commercial test kits and a pH meter. Although the SERS substrates are rigid, their small size allows the wearable device, composed of PDMS, skin adhesive, and Kapton tape, to still exhibit flexibility. It is worth noting that the chips should be stored under vacuum or immersed in ethanol to minimize Ag oxidation. Following a similar approach, an Au nanosphere cone array was fabricated by depositing Au onto a Si nanocone array (Figure 18b). (335) The nanogaps between the Au nanosphere cones yield high SERS enhancement. The Au SERS substrate enabled the detection and quantification of acetaminophen in the concentration range of 0.5–100 μM with a low detection limit of 0.13 μM. A human subject study showed that the acetaminophen in sweat reached a concentration of 36.8 μM after the drug intake and decreased after ∼90 min. Electrospun thermoplastic polyurethane nanofibers sputter-coated with 30 nm Au film were demonstrated as a flexible and stretchable SERS substrate (Figure 18c). (339) The fiber intersections provide strong SERS enhancement. The SERS intensity collected from the substrates created with polyurethane microfibers was 5 times lower than that with nanofibers, highlighting the importance of nanoscale scaffold. The SERS substrates were modified with 4-mercaptopyridine (4-Mpy) and 4-mercaptobenzoic acid (4-MBA) to quantify pH using buffer solutions (pH 4–8). The peak intensity ratio calculated as I (pH-active peak)/I (reference peak) of 4-Mpy and 4-MBA was used to quantify pH. The pH sensing performance remained stable with 300 cycles of 50% stretch, demonstrating the stretchability of the SERS substrates. The quantification based on the SERS intensity ratio could be an effective strategy to provide stable sensing performance under stretch by eliminating the variations in the absolute SERS intensity induced by nanostructure changes. Another report showed the electrospun poly(vinyl alcohol) nanofibers could be removed after the sputter disposition of 150 nm Au to yield Au nanomesh as a SERS substrate (Figure 18d). (340) The EM hotspots in crescent-shaped goldmesh are primarily localized at the sharp edges of the nanowire. The Au nanomesh provided the SERS enhancement factor of ∼108 and detection of R6G at the low concentration of 10 nM. The SERS intensity remained stable after 1000 crumpling cycles, likely due to negligible changes in the density of EM hotspots after crumpling cycles. The Au nanomesh adhered to a prestretched PDMS substrate and exhibited stable SERS intensity after 1000 stretching cycles with 50% strain. This confirms that laminating unstretchable nanostructures onto a prestretched elastomer substrate could be an effective strategy to provide device stretchability and improve sensing stability. In addition, the detection of urea (1–100 mM), ascorbic acid (1–100 nM), and 3,4-methylenedioxymethamphetamine at low concentrations of 520 nM and 5.2 μM in water was also demonstrated.
The bottom-up approach for fabricating a wearable SERS substrate involves the synthesis of plasmonic nanomaterials with control over size, shape, and material composition through chemical processes, followed by their deposition or self-assembly onto a substrate. Figure 18e shows a layer of ordered Ag nanocube superlattice, self-assembled on a flexible 200 nm thin poly(methyl methacrylate) (PMMA) film to yield a conformal contact of the SERS substrate with the skin. (337) The closely packed Ag nanocube array with a gap size of ∼1 nm was first formed at the water–air interface and then transferred to the PMMA film via the Langmuir–Blodgett deposition. The SERS substrate enabled the detection of crystal violet (CV) at a low concentration of 1 nM with an enhancement factor of ∼107. In a wearable device, a guard ring was placed around the 2 mm SERS substrate to reduce the strain around the silver nanocube array and minimize deformation effects. The SERS intensity remained stable under ∼30% strain and after 1000 stretching cycles. The sweat sensor was calibrated to detect nicotine in artificial sweat at the concentration range from 100 nM to 10 μM. In vivo demonstration showed that the sweat sensor could monitor the drug concentration changes in iontophoresis-induced sweat on a healthy human subject. The SERS substrate was also functionalized with 4-Mpy to quantify sweat pH from pH 4 to pH 6.5. An omnidirectional plasmonic nanovoids array (OPNA) also showed stable SERS performance under various deformations (Figure 18f). (342) The OPNA was prepared by self-assembling a monolayer of Ag nanospheres with an average diameter of 65 nm onto the curved surface of the pockets decorated microscale semisphere retina. The gap between Ag nanospheres is around 5 nm. The pocket surface was coated with ∼50 nm Au and ∼10 nm SiO2 film to further enhance the plasmon coupling and SERS intensity. The resultant strong electromagnetic field allows the OPNA to detect R6G at an ultralow concentration of 10–16 M with an enhancement factor of 108. The EM hotspots inside the rigid pockets remained stable upon stretching, providing consistent SERS intensity after 40% stretch. The consistent SERS intensity under bending with the angle ranging from 0° to 45° could be ascribed to the omnidirectional characteristics of the nanovoids array. The hydrophilic SERS test domain was confined by hydrophobic surroundings for sweat collection and concentration. The OPNA SERS substrate functionalized with 3, 3′-dithiodipropionic acid di(N-hydroxysuccinimidyl ester) enabled the sensitive and specific detection of dopamine at a low concentration of 1 pM. In addition, 4-acetamidobenzenesulfonyl azide-coated OPNA SERS substrate was used to detect and quantify H2S from 1 ppb to 100 ppm. In addition to self-assembly, as-synthesized Au nanorods could be uniformly deposited onto a flexible chromatography paper as a SERS substrate (Figure 18g). (336) The uniform disposition of Au nanorods on the paper results from the combination of weak interactions, including electrostatic interaction and van der Waals forces. (343,344) The SERS substrates provided consistent SERS intensities measured from different regions and different batches. A ratiometric SERS approach was utilized to eliminate the absolute SERS intensity variations associated with the laser power, alignment, and focus in wearable applications. This approach ensures consistency in the quantification of analytes with benchtop and portable Raman spectrometers, obviating the need for recalibration with the portable spectrometer. The plasmonic paper enabled the quantification of uric acid at the concentration range from 1 μM to 100 μM using the SERS intensity of uric acid normalized with that of PDMS encapsulation coating. The ratiometric SERS intensity remained stable at 45 °C high temperature and under 30% strain. Au nanospheres can also be in situ synthesized onto the surface of two-dimensional transition metal carbon/nitrides (MXene) to form a flexible SERS substrate (Figure 18h). (345) Alkaline treatment of TiVC membranes introduced hydroxyl groups on the MXene surface and facilitated the reduction and nucleation of Au NPs. The Au nanosphere size and gap dimension between the nanospheres could be controlled by varying the growth time. The optimized SERS substrate with dense EM hotspots enabled the detection of R6G at a concentration of 10–15 M with SERS enhancement factor of 8 × 1010. The detection of several drug analytes was demonstrated in artificial sweat, including nicotine, methotrexate, nikethamide, and 6-acetylmorphine at the concentration range from 10 nM to 1 mM.
In wearable sweat sensors, microfluidics plays an important role in enabling continuous monitoring of analytes, including sample collection, transport, and storage, while minimizing the mixing of sweat generated at different times. Additionally, a microfluidic module can be employed to quantify sweat volume and secretion rate, which are potentially linked with the analyte concentrations in sweat. Common soft microfluidic devices are made of PDMS, showing the capability of collecting and transporting sweat (Figure 18i). (341) The hydrophobic PDMS surface needs to be treated with plasma to become hydrophilic, improving sweat sampling and transport. The number of inlets can affect the kinetics in refreshing the sensing chamber and temporal resolution in quantifying time-varying analyte concentrations. The authors demonstrated the continuous monitoring of varying concentrations of lactate with a temporal resolution of 8 min (Figure 18j). Paper-based microfluidics was also utilized in wearable SERS sensors, which has several advantages over plastic-based systems (Figure 18k). (336) The chromatography paper can actively capture and transport sweat through capillary action without the need for additional force, for example, the pressure induced by sweat glands. This reduces the flow impedance while the sweat transports across the microfluidic channel, which is important for accurate quantification of sweat volume and secretion rate. In addition, the high surface area of paper substrates allows for high-density immobilization and storage of functional materials and chemical reagents. The serpentine design could provide the device flexibility and stretchability. Two operation modes for continuous monitoring were demonstrated using uric acid as a model target, including continuously scanning the same sensor and scanning several sensors within the same device at the end time. The ratiometric SERS intensity could reach the equilibrium state within 5 min, determining the temporal resolution in these measurements (Figure 18l). The ratiometric SERS approach provided the wearable sensors under mechanical strain and operation temperature with stable analyte quantification. In addition to paper, other porous substrates can also enable highly uniform nanostructure immobilization and easy integration with microfluidic platform. (346−353)
All the components in a wearable device, including SERS sensors, microfluidic module, encapsulation coating, laser blocker, and skin-interfaced adhesive, need to be rationally designed to provide reliable device performance for in situ monitoring of target analytes. Many of these components can draw design inspiration from advances made in the development of soft, wearable electronic devices. (328,354−360) Several challenges and opportunities are present in facilitating the deployment of SERS-based wearable sweat sensors in the real world. Several reports highlighted the potential utilization of portable Raman spectrometers (Figure 18m), (335,341,345,361) which could be further improved for higher sensitivity and spectral resolution, and miniaturized into a wearable form factor. Only a few reports employed surface functionalization to enable sensitive and specific detection of targets (Table 2), which could be explored further to expand the capability of wearable SERS-based sweat sensors. For example, the utilization of stable biorecognition elements, such as molecularly imprinted polymers and aptamers, can improve sensitivity and specificity in quantifying analytes in body fluids. (362−365) Most in vivo demonstrations rely on measurements of sweat generated through physical exercise. The SERS sensors integrated with a sweat induction module would be beneficial for their convenient deployment and continuous monitoring in vivo (Figure 18n). (337) Additionally, the chemical, mechanical, and thermal stabilities of wearable SERS sensors need to be evaluated, considering the harsh conditions in wearable applications.
5.5. Widefield and Holography Raman Instrumentation
The acquisition time in SERS is a critical parameter that influences the sensitivity and reliability of the technique. SERS relies on the enhancement of Raman signals through the interaction of molecules with plasmonic nanostructures, and the acquisition time can significantly affect the quality of the obtained spectra. Short acquisition times are desirable for rapid analysis, especially in dynamic environments, for monitoring fast processes or for monitoring thousands of events, while longer acquisition times can improve signal-to-noise ratios but may lead to sample degradation or photodamage. State of the art Raman systems with highly efficient plasmonic materials can obtain the SERS spectrum of a “good” SERS molecule in 100 ms. However, standard acquisition times for most molecular systems rage between 1 to 10 s, good for many detection and characterization applications but very slow for, for example, biomedical applications in the fields of infectious disease diagnosis or liquid biopsy of cancer, where a large sample of fluids should be extensively screened or for biomedical imaging, where point-by-point (line-by-line with streamline accessories) not only are very slow but usually destroy the sample.
Widefield SERS techniques have emerged as a solution to the limitations posed by traditional point-by-point scanning methods, which often require extensive acquisition times. Widefield SERS imaging allows for the simultaneous collection of spectra from multiple locations across a sample, significantly reducing the overall measurement time. (367) This approach is particularly advantageous for applications requiring high-throughput analysis, such as screening large libraries of NPs or biomolecules. By averaging multiple acquisitions, widefield SERS can enhance the reliability of the results while maintaining a reasonable acquisition time.
The implementation of widefield SERS involves several critical components and methodologies that enhance its effectiveness and applicability. In widefield SERS, the entire sample is illuminated simultaneously, which contrasts with traditional point-scanning methods. This approach not only increases the imaging speed but also enhances the spatial resolution of the Raman signals collected across a large area. (368,369) The experimental setup typically includes a laser source, a microscope equipped with appropriate optics, and a metal oxide semiconductor (MOS) charge-coupled device (CCD) camera as a detector (Figure 19a). The laser is used to excite the SERS-active NPs, while the microscope facilitates the collection of scattered light from the sample. The use of spatial light modulators (SLMs) or digital micromirror devices can further enhance the imaging capabilities by allowing for patterned illumination, which helps reduce photobleaching and improve signal-to-noise ratios. This modulation of the illumination can be crucial for optimizing the imaging conditions and enhancing the quality of the acquired data. In addition to the hardware components, the integration of computational techniques, such as machine learning algorithms, can facilitate the analysis of complex SERS data. These algorithms can assist in identifying spectral features associated with specific molecular signatures, thereby improving the accuracy of diagnostics and enabling the development of personalized medicine approaches. (369) The combination of widefield SERS with advanced data analysis techniques holds great promise for enhancing the diagnostic capabilities of this technology. In practical applications, widefield SERS has been successful to explore large areas very fast and has a lot of potential for tissue diagnosis and anticounterfeiting among other applications (Figure 19b). (367)
Figure 19
Figure 19. Widefield and holography Raman imaging. (a) Schematic widefield microscope extended with “beam homogenization” and “imaging and spectroscopy” modules. The beam homogenization module ensures a flat illumination profile over the entire field of observation to allow quantitative SERS intensity measurements. The imaging and spectroscopy unit simultaneously records an image of the sample plane alongside a spectrally dispersed copy of said image on the same sCMOS camera. This combination ultimately allows extracting single-particle spectra from the camera recordings. Adapted with permission from ref (369). Copyright 2022, John Wiley and Sons. (b) Optical image and single shot SERS imaging of large plasmonic surfaces of 3 mm × 3 mm and the corresponding and SERS spectra taken along the blue lines marked. The bold spectrum represents the mean spectrum. Adapted with permission from ref (368). Copyright 2022, American Chemical Society. (c) Schematic of the spectrally resolved holographic widefield microscope composed of a Michelson and a shearing interferometer enabling simultaneously spectrally resolved imaging and image-phase measurements. The sample is widefield illuminated and the red-shifted SERS signal separated from residual laser light with a dichroic beamsplitter and a long-pass filter. After propagating through a Michelson interferometer, a conjugate image is formed that is relay-imaged onto an sCMOS camera. A 2D 0-π phase grating is placed slightly offset with respect to the conjugate image plane and generates multiple diffraction orders which propagate through the relay imaging system. A hard aperture placed into the Fourier plane isolates the four first diffraction orders which ultimately self-interfere on the camera. The insets highlight the grating-induced change in PSF (left vs right) alongside a schematic of the Fourier filter. (d) Live cell SERS particle tracking. The SERS signal (pink), recorded at a fluence of 1.8 kW/cm2 and an integration time of 250 ms, is superimposed onto a brightfield image, recorded using Koehler illumination with a 470 nm fiber-coupled LED, of the cells. The trajectories of individual SERS particles are color-coded to show the respective z-positions which are obtained by 3D localizing the particles from image stacks generated via numerical propagation. 40 time-points are recorded per minute. (c, d) Adapted with permission from ref (371). Copyright 2020, Springer-Nature.
SERS holography is another innovative technique that addresses the challenges associated with acquisition time in SERS imaging. Again, unlike conventional SERS imaging, which typically involves lengthy point-by-point scans, SERS holography enables the capture of three-dimensional spectral information in a single shot. This method utilizes interference patterns created by coherent light sources to reconstruct the SERS signal across a wide field of view, allowing for rapid imaging of complex samples (Figure 19c). (370) The ability to obtain comprehensive spectral data quickly makes SERS holography particularly valuable for applications in live cell imaging and real-time monitoring of biochemical processes. For example, by using SERS holography it is possible to record the trajectory of one or several plasmonic particles inside a fluid or a cell (Figure 19d). (371) Also, the dynamics of SERS signals can also be influenced by the acquisition time. For example, dynamic SERS strategies have been employed to capture transient events and fluctuations in SERS intensity, providing insights into the interactions between analytes and plasmonic substrates. (372) By optimizing acquisition times, it is possible to enhance the temporal resolution of SERS measurements, enabling the detection of rare events at the single-molecule level.
In short, acquisition time is a pivotal factor in SERS applications, impacting both the quality of the spectral data and the feasibility of real-time monitoring. Advances in widefield SERS and SERS holography offer promising solutions to the limitations of traditional acquisition methods, enabling rapid and reliable analysis of complex samples. As the field continues to evolve, optimizing acquisition times will remain a key focus for enhancing the capabilities of SERS in various applications, including biomedical diagnostics, environmental monitoring, and materials science.
6. Recent Advances in Spectral Analysis
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6.1. SERS Frequency analysis
6.1.1. General Methods for SERS Frequency Analysis
SERS frequency reflects the difference between the excitation laser energy and the energy of photon emitted from the excited molecule, which corresponds to molecular vibrations unique to each (bio)chemical species. (373−379) Collectively, SERS frequencies across a range of wavenumbers form a SERS spectrum that encodes an enormous amount of molecular vibration information. (380,381) SERS spectral changes mainly exist in two form: wavenumber shift and peak intensity change. Wavenumber shift can be further categorized into red-shift and blue-shift, which correspond to a decrease and an increase in vibration frequency and energy, respectively. (382,383) Meanwhile, peak intensity change reflects the vibration polarizability and/or the change in the population of the adsorbate. (375) In biomedical application aspect, such spectral changes indicate the presence of the target analyte by 1) directly observing their intrinsic vibration fingerprint, and 2) indirectly indicating chemical interaction and/or reaction occurring in the presence of the target analyte. Hence, frequency shift analysis plays a vital role in establishing accurate model for qualitative and quantitative (bio)chemical analysis for biomedical applications. Generally, frequency shift analysis consists of (a) spectral preprocessing, (b) peak deconvolution and measurement, and (c) establishing the relationship between the SERS frequency shift and the presence of the target analyte (Figure 20a). (384)
Figure 20
Figure 20. Conventional SERS frequency analysis strategies. (a) Summary of conventional steps for SERS frequency analysis. (b) Schematic illustration of spectral preprocessing strategies. (c) Peak identification and deconvolution to unravel the reaction events at Ag-MP@ZIF by deconvolution of SERS spectra from 1280 to 1400 cm–1. Reprinted and adapted with permission from (c) ref (385). Copyright 2020, American Chemical Society.
6.1.1.1. Spectral Preprocessing
SERS spectral preprocessing step is crucial in removing signals originating from the instrument or the sample that is irrelevant to the presence of the target analytes, ensuring a “clean” spectra for accurate frequency shift analysis. (384) A standard spectral preprocessing includes spike removal, wavenumber and intensity calibration, and baseline correction (Figure 20b). Specifically, the spikes are detected by their abnormal narrow and intense spectral features and can be removed from the spectra by linear interpolation based on the two boundary points of the spike. (386,387) Subsequently, wavenumber and intensity calibration steps ensure spectra are comparable among different Raman systems, which are crucial for biomedical applications because the analytical result is supposed to be identical by different instruments, as long as the measurement conditions such as excitation wavelength and laser power are the same. Conventionally, using a reference/standard material, the wavenumber axis is calibrated by fitting a function between the measured and theoretical positions of the well-defined Raman bands of a wavenumber standard, while the intensity axis is calibrated by dividing the measured Raman intensities by the intensity response function of the instrument. (388) Next, baseline correction serves two main purposes: removing signals stemming from the SERS substrate and removing the fluorescence originating from the sample. Although numerous baseline correction methods, such as sensitive nonlinear iterative peak clipping, asymmetric least-squares (ALS) smoothing, modified polynomial fitting, and multiplicative scattering correction (MSC), have been developed, the choice of baseline correction methods is highly scenario-specific and not universal. (389−395) It is generally accepted that selection of baseline correction method is trial-and-error and the best method is determined based on the result of subsequent analysis. Beyond the above-mentioned preprocessing steps, other processing methods, such as spectra smoothing, and normalization, are optional preprocessing methods (Figure 20b). For instance, smoothing is only useful when spectral noise significantly affects subsequent peak wavenumber and intensity determination, because smoothing can introduce artificial correlations into the noise structure, and subsequently adversely affect spectra analysis and analytical model construction. (396,397) Meanwhile, normalization aims to exclude the effect of laser power fluctuations and changes in the laser focusing by dividing the entire spectra by a number, such as the area under the curve, or highest peak intensity. (398−400) Collectively, a robust spectral preprocessing step is critical in ensuring high-quality spectra for subsequent peak identification and analytical model construction.
6.1.1.2. SERS Peak Deconvolution and Measurement
SERS peak measurement aims to obtain peak features such as peak center, intensity, full-width at half-maximum intensity (fwhm), and peak area, which are crucial for subsequent establishment of calibration curve. Conventionally, this is done by direct measurement on graphing/plotting software. For SERS spectral region containing multiple overlapping peaks, peak deconvolution must be done prior to peak measurement by fitting the region of interest with multiple peaks such that their accumulative signal is approximately equal to the experimental spectra. (401,402) The most common peak deconvolution method is Gaussian fitting, which accounts for effects such as natural broadening, Doppler effect, materials effect, and Raman instrument effects. For example, peak deconvolution assists in deciphering the chemical species present during different reaction stages of carboxylation by identifying the emergence of two sets of irreversible νCOO- peaks (Figure 20c). (385) In addition to Gaussian fitting, there exist other fitting methods such as Lorentzian, Voigtian and Pearson type IV that can account for hybrid peak profile and/or peak asymmetry, yet these methods remain limitedly explored for practical SERS frequency shift analysis. (403−405) Accurate peak feature measurement is crucial for subsequent establishment of relationship between the SERS frequency shift and the presence of target analytes.
6.1.1.3. Standardization and Calibration of SERS Frequency Shift among Samples
Standardization and calibration of SERS frequency shift among samples is conventionally done by finding a mathematical formula to express the concentration of the target analytes from measured peak features such as peak center, intensity, and fwhm. Here, three methods are outlined, namely: (i) external standard calibration, (ii) internal standard calibration, and (iii) standard addition.
| i. | External standard calibration. In an external standard calibration, SERS spectra are obtained from a series of standard solution prepared separately from the sample (Figure 21a, i). A plot of SERS peak features response versus known analyte concentrations is used to produce a calibration curve, which allows unknown analyte concentrations to be calculated by interpolation. The most common method to find the formula of the calibration curve is the least-squares method, in which a “best” straight line among the data points is obtained, which minimizes the sum of squares of vertical different from each point to the straight line. For example, SERS peak intensity at 610 cm–1 of R6G demonstrates a linear relationship with log[concentrations] ranging from 10–10 to 10–7 M on a Ag nanocubes-based superhydrophobic platform (Figure 21a, ii). (406) External standard calibration, however, in many cases are prone to errors due to signal interferences from other compounds in the sample matrices, and the instability/mismatch of chemical form of standard in the sample matrices. Thus, using an internal standard is an alternative method to compensate for certain types of error occurring both in the analyte and reference measurement. | ||||
| ii. | Internal standard calibration. For internal standard calibration, a known amount of reference species is added to sample, standard and blank, from which a calibration curve is constructed to establish the relationship between SERS peak ratio of the analyte/reference signal and the analyte concentration in the standards (Figure 21b, i). (407) This method ensures that both reference and analyte species possess similar chemical and physical properties because they coexist in a sample matrix. One common strategy employing internal standard calibration is the use of SERS tags that have strong signal in the biologically silent region (1800–2800 cm–1) to avoid interfering signals stemming from biomolecules. For example, mercaptobenzonitrile (MBN) was employed as an internal standard to monitor a ratiometric signal between MBN’s 2223 cm–1 and 2-naphthylthiol (NAT)’s 1378 cm–1 for in vitro detection of Cu2+ in Wilson’s disease (Figure 21b, ii). (408) Apart from SERS tag, isotopologues method can also be employed, in which a stable artificial isotope is introduced to facilitate monitoring the concentration of the target analyte. For example, the use of deuterium isotope codeine-d (6) significantly improved the prediction accuracy and root-mean-square error of prediction (RMSEP) in quantifying codeine in both water and human plasma. (409) Such method is especially useful when other internal standards do not yield a linear relationship due to unequal competition between the target analyte and the internal standard on the SERS substrate. | ||||
| iii. | Standard addition. Standard addition is an alternative method to construct the calibration curve when it is difficult or impossible to duplicate the sample matrix. (410,411) Specifically, SERS peak features are monitored as the test sample is spiked with a known amount of standard solution of the analyte (Figure 21c, i). The x-intercept of the calibration curve corresponds to the negative of the analyte’s concentration in the original sample. For example, standard addition was employed to construct a calibration curve for quantification of an antibiotic nitroxoline at micromolar concentration range in urine (Figure 21c, ii). (412) It is of note that standard addition method can also be used to validate the calibration curve and the quantification result by calculating the recovery rate (%) from the ratio between the difference between observed and measured concentration and the spiked concentration. Collectively, external standard calibration, internal standard calibration, and standard addition demonstrate traditionally manual SERS frequency shift analysis for analyte concentration determination. | ||||
Figure 21
Figure 21. Standardization and calibration of SERS frequency shift among samples. (a) (i) Scheme illustration of external standard calibration method and (ii) calibration for R6G ranging from 10–7 to 10–16 M using 610 cm–1 intensity. (b) (i) Scheme illustration of internal standard calibration method and (ii) calibration for Cu2+ quantification showing SERS spectra and ratio (I2223/I1378) as Cu2+ concentration ranging from 0 to 18 mM. (c) (i) Scheme illustration of standard addition method and calibration of nitroxoline in urine and SERS spectra upon spiking different concentration of nitroxoline. Reprinted and adapted with permission from (a) ref (406), (b) ref (408), and (b) ref (412). Copyrights 2013, 2016, 2021, American Chemical Society.
6.1.2. Machine Learning for Frequency Shift analysis
In biomedical applications, traditional manual SERS frequency shift analysis often has limited performance due to 1) the convoluted analyte signals arising from numerous interfering species and 2) a large amount of time is required to process large volumes of data. (413) Recently, machine learning (ML) algorithms–smart programs based on logic and mathematics - are increasingly employed for frequency shift analysis to identify minute convoluted spectral changes, recognize patterns, and handle large data set. (414) Common machine learning algorithms employed for frequency analysis can be classified into two groups: unsupervised and supervised (Table 3). (415−417) Unsupervised machine learning involves training algorithms on spectra without labeled responses, aiming to identify hidden patterns or intrinsic structures, such as clustering similar spectral profiles. (418,419) Supervised machine learning trains algorithms on labeled data, where the model learns to predict the output from input data by using known input-output pairs, such as identifying biomarkers/disease states from spectral features. (420−422) Selecting the right machine learning algorithm is critical to construct an accurate and robust model for SERS frequency shift analysis.
Table 3. Common Machine Learning Algorithms and Their Signature, Advantages, Disadvantages, and Usual Sample Size (Per Class)
6.1.2.1. Unsupervised Machine Learning
Unsupervised machine learning algorithms are particularly beneficial for SERS frequency shift analysis due to their simplicity yet effective pattern recognition, data exploratory and data visualization. Three commonly used unsupervised machine learning algorithms will be discussed: principal components analysis (PCA), uniform manifold approximation and projection (UMAP), and hierarchical clustering analysis (HCA) (Table 3). (423,428,446−449)
The most commonly used unsupervised algorithm is PCA, which reduce data dimensionality by capturing maximum variance among variables and transforming it into principal components containing useful data. (423,425,427) As the data dimensionality reduces, a 2D or 3D PCA score plot is often employed to visualize data clustering and determine whether the spectra differences among clusters are statistically significant. In one study, a 3D PCA was employed to visualize the clear distinction among spectra of fentanyl (FE), morphine (HER), ketamine (KET), and ternary mixture samples, confirming the capability of SERS platform for drug detection and differentiation (Figure 22a). (424) Besides the data clustering and visualization, PCA is also well-known for its conjunctive use with a supervised algorithm to avoid overfitting due to the curse of dimensionality and to accelerate the model construction process, which is especially beneficial for SERS data due to its inherently huge amount of variables (each wavenumber is considered a variable). For example, PCA was employed prior to support vector machine (SVM) to reduce the data dimensionality of a SERS double-fingerprint (∼2800 variables) to only 5 PCs that captures only the most important spectral features for subsequent construction of model for simultaneous quantification of SO2 and NO2 in the presence of excessive CO2 as interference. (426) It is of note that PCA can only capture linear correlation and thus has limited flexibility and might not be able to maintain both local structure (relationship and patterns among nearby/similar spectra) as well as global structure (overall arrangement and relationships among all spectra in the data set).
Figure 22
Figure 22. Unsupervised machine learning for SERS frequency shift analysis. (a) 3D PCA score plot of the ternary mixture (FE: 0.1 μg/mL, HER: 10 μg/mL, KET: 10 μg/mL) and its single components and the corresponding LLI SERS spectra. (b) UMAP plot showing an overlaid density contour plot and pixels reordered in correct spatial correlation and colored by clusters identified in UMAP. (c) Hierarchical clustering analysis of measured MPY SERS, which categorizes the bacteria species on three main levels using ECM surface chemotype-based classification factors, namely, surface charge, overall ECM chemical characteristics, and type and number of interacting functional groups. Reprinted and adapted with permission from (a) ref (424), (b) ref (429), and (c) ref (432). Copyright 2023, American Chemical Society.
UMAP is an alternative powerful dimensionality reduction technique that excels in capturing complex, nonlinear relationship and preserve both local and global structures. (428−430) In the aspect of SERS frequency shift analysis, UMAP can cluster pixels on a Raman map to provide information on sample heterogeneity. For example, UMAP was employed to understand the spatial distribution and composition of complex biological samples, such as cardiac tissue, using a Raman map (Figure 22b). Specifically, spectra from individual pixel on a Raman map were distinctively segregated into 8 clusters with intracluster spectra being similar to each other. Subsequently, spectra from each cluster were analyzed to identify the typical area with higher intensity and associate the cluster’s origin with the type of tissue, thus enabling spatial mapping and visualization of cardiac structures and compartments. (429) Such spatial mapping of specific peaks enables locating myocardium, collagen, and blood cells, demonstrating UMAP’s effectiveness in identifying and spatially characterizing tissue components. Despite being a powerful clustering algorithm, it should be noted that the high flexibility and complexity of UMAP might cause overfitting issue and make the result harder to be interpreted. Hence, nonlinear UMAP algorithm requires much larger data set (50 000–5 000 000 spectra per class) comparing to linear algorithms such as PCA and HCA (10–100 spectra per class).
To explicitly illustrate the relationship among spectra, HCA is often employed because it provides a dendrogram that indicates the distance or dissimilarity between clusters of spectra, facilitating the interpretation of factors affecting the clustering. (431−433) In addition, HCA can also work directly with the full spectra, preserving all features without the need for dimensionality reduction, which is beneficial for biomedical applications that require the use of all spectral information. In a study using SERS for bacteria differentiation, HCA separated 600 spectra from 6 bacteria species into distinct clusters, revealing a three-level separation based on 1) surface charge, 2) overall biochemical characteristics, and 3) type and number of functional groups (Figure 22c). (64) These examples collectively demonstrate the ability of unsupervised machine learning algorithms for pattern recognition, data clustering and visualization. Despite these benefits, unsupervised model can be incompetent for complex tasks when there are multiple sources of interference such as interfering substances, background noise, and data collection conditions and due to the lack of labeled data for guidance.
6.1.2.2. Supervised Machine Learning
Supervised machine learning algorithms can significantly improve SERS analysis accuracy using labeled data sets, such as known analyte’s molecular structure, concentration, and sample’s disease status. To date, various ML algorithms have been developed, ranging from simple and low flexibility such as partial least-squares (PLS) to more complex and high flexibility such as support vector machine (SVM), tree-based algorithms, and neural network-based algorithms (NN) (Table 3). (382,396,420,422,450−453) In general, simple algorithm performs better when there is a limited number of sample and/or the relationship between SERS frequency shift and analyte concentration is linear, whereas complex algorithm is more suitable for a larger data set and/or nonlinear spectra-analyte concentration relationship. It is of note that all these algorithms are applicable for both qualitative (e.g., classification of disease diagnosis) and quantitative (e.g., quantification of biomarkers) spectral analysis.
PLS is one of the simplest machine learning algorithms. It aims to find a set of latent factors which best account for the maximum multidimensional covariance between the input SERS spectra and the label, followed by constructing regression/classification models. (382,434−436) Notably, the ability to handle highly collinear and noisy data makes PLS a powerful tool for SERS spectra analysis. For instance, PLS regression was employed to construct calibration curve for quantitative analysis of an enantiomers mixture (d- and l-tryptophan) using nanoporous Au NPs (Figure 23a). (434) The constructed calibration demonstrates an excellent fit, with a high cross-validation value R2 of 0.96, and the ability to accurately quantify mixture of unknown component at absolute error of ∼1%. In another study, PLS discriminant analysis (PLS-DA) was employed to analyze 501 breath samples and construct COVID-19 screening model using the SERS superprofile measured on an array of receptors, achieving 96.2% sensitivity and 99.9% specificity. (436) These examples thus demonstrate the PLS algorithm capability to construct accurate qualitative and quantitative models from multivariate data sets.
Figure 23
Figure 23. Supervised machine learning for SERS frequency shift analysis. (a) PLS regression plot of measured against actual mol % L-TRP. The calibration curve is constructed from spectra collected in varying mol % L-TRP mixtures at 10 mM total [TRP] and comparison of measured vs actual mol % L-TRP in different test samples using the NPGB/EC-SERS platform. (b) Support vector machine classification for differentiation between SERS spectra collected from healthy control and prenatal disease. (c) Confusion matrix of averaged classification outcomes across 100 model iterations using a random forest (RF) classifier. The F1 scores are indicated in brackets. Reprinted and adapted with permission from (a) ref (434), (b) ref (437), and (c) ref (432). Copyrights 2018, 2021, 2023, American Chemical Society.
To construct nonlinear or more complex relationships, machine learning algorithms with higher flexibility is often preferred, such as SVM, tree-based, and neural network-based algorithms. Support vector machine (SVM) is well-known for its capability to handle small data set (as small as a few tens of spectra) with nonlinear relationships, by projecting data onto a higher dimension plane and find the optimal boundary to separates labeled groups. (425,454) A critical example showcasing SVM superiority is for prenatal diseases diagnosis using a paper-based SERS, achieving >93% accuracy with a training data set of 40 samples with 40 spectra for each sample (Figure 23b). (437) Another frequently used algorithm is tree-based algorithms, such as random forest and gradient boosting, work by constructing multiple decision trees and aggregating their outputs for improved accuracy and reduced overfitting. (438−442) In one study, random forest were used to construct model for differentiating among 6 bacteria species by SERS spectra changes induced by the interaction between the extracellular matrices and 4-mercaptopyridine (MPY)-functionalized Ag nanocubes, achieving >98% classification accuracy (Figure 23c). (432) Lastly, neural network-based (NN-based) algorithms offer highest flexibility to model highly complex data and capture intricate patterns by constructing multiple interconnected layers of nodes that process input spectra through weighted connections. (374,443,444) For example, a convolutional neural network model was constructed for simultaneous detection of 6 types early stage cancers by analyzing SERS profiles of exosomes at >95% accuracy. (445) Despite offering great potential for SERS spectra frequency analysis and model construction, it is noteworthy that overfitting due to insufficient number of spectra is a persistent issue for supervised algorithm, especially for tree- and neural network-based algorithms which requires hundreds to tens of thousands spectra. In addition, overfitting also stems from inadequate model evaluation/validation with untrained sample. Hence, extra precautions need to be taken at every step from sampling and data collection, model building, and model evaluation to ensure a robust machine learning model for SERS frequency shift analysis.
6.1.2.3. Enhancing Interpretability of Machine Learning Analysis
Although the advances in machine learning algorithm enable accurate SERS frequency analysis and achieve unprecedented analytical performance, models constructed using machine learning algorithm are usually referred to as a “black box” with highly complicated mathematics calculations and limited interpretability. This is thus raising a concern on reliability of the models, whether the analyses are based on (bio)chemical recognition event and limit the (bio)chemical insight conventionally obtained from manual analysis of SERS fingerprint. Here, three main approaches with increasing transparency to enhance the interpretability of machine learning-SERS frequency shift analysis will be discussed: (i) feature importance ranking, (ii) domain knowledge-driven machine learning, and (iii) chemical simulation.
| i. | Feature importance ranking. Feature importance ranking algorithms enhance the interpretability of models by identifying the specific wavenumbers or spectral regions that significantly impact the model’s prediction, ensuring that the models are based on meaningful spectral features rather than random noise (Figure 24a, i). The most commonly used algorithms for feature importance ranking is Shapley additive explanations (SHAP), which calculates the effect of each variables on the output values to evaluate their importance. (452,455,456) For instance, SHAP was employed to calculate the feature importance of a convolutional neural network model for classification of samples with high (10–1 to 10–3 M), medium (10–3 to 10–5 M), and low concentration (10–6 to 10–8 M) of 2,3-dihydroxybenzoic acid (2,3-DHBA), a typical bacterial biomarkers and metabolites (Figure 24a, ii). (457) Specifically, SHAP identifies wavenumber of high contributions at 438, 1236, 1442, 1572 cm–1, which are close to SERS peaks of 2,3-DHBA, thus indicating that the spectral classification is reliable because it relies on the spectral features of the biomarker and not random noise. In addition to SHAP, there are other feature importance ranking models such as local interpretable model-agnostic explanations (LIME) and contrastive explanations method (CEM), yet their application for Raman and SERS spectral analysis remains unexplored. (458,459) The aforementioned algorithms for feature importance analysis are especially useful for complex algorithms, thus we recommend studies employing machine learning for frequency analysis to employ these methods more frequently to ensure model reliability, interpretability, and accelerate translation of machine learning-SERS sensor into practice. | ||||
| ii. | Domain knowledge-driven machine learning. There is an increasing demand for models with an inherent capability to output feature importance concurrently with the target properties (Figure 24b, i). This capability provides a direct correlation between SERS peak features and the underlying chemistry of analysis. Understanding which spectral features are most influential aids in interpreting the chemical composition and interactions in the sample. Such models enhance interpretability and are highly valuable in applications like biomedical diagnostics and chemical analysis. A simple algorithm with inherent capability to output feature importance is PCA, which generates loading plots that capture the contribution of each wavenumber to the respective PCs. (425,432) The loading plots have been employed in many studies, for example in wine flavor classification to unravel the spectral changes induced by different types of interactions such as pi-pi stacking, dipole–dipole interaction, and H-bonds (Figure 24b, ii). (425) Another commonly algorithm capable of outputting feature importance is symbolic regression, such as sure independence screening and sparsifying operator (SISSO), which identifies the important features and finds the best mathematical expressions between these variables and the target properties. (441,460−462) For example, SISSO was employed to establish an interpretable relationship between Raman signals and pure metal–adsorbate adsorption energy, highlighting the strong influence of a specific νCO vibration mode for the prediction of adsorption energy. (460) Importantly, the highly interpretable mathematical formulas established by SISSO enable transferring to a series of metal/alloy surfaces. Collectively, the above examples of algorithms highlight the potential of “transparent box” model to not only yield accurate SERS frequency analysis, but also provide significant chemical insights and enable transfer learning and model extension to similar spectral analysis tasks. | ||||
| iii. | Chemical simulations. Beside feature importance ranking and domain knowledge-driven machine learning, chemical simulation is a powerful tool to unravel the mechanism behind observed spectral changes and ML-based decisions, such as types of interaction involved, analyte configuration and orientation, and chemoselectivity. The most commonly used simulation method is density functional theory (DFT), which provides theoretical molecular vibration and SERS spectra with high accuracy for the validation of spectral features corresponding to the recognition event. For example, DFT simulation was employed to corroborate with the spectral changes identified on experimental SERS spectra and PCA loading plot to confirm the ring complexation phenomenon (Figure 24c). (426) In the same study, to the authors calculate and compare the interaction energy of different receptor-analyte binding configuration to explain for the accelerated spectral stabilization. DFT simulations can also give insight into analyte adsorption orientation, which significantly influence SERS spectra. In particular, DFT-simulated spectra were employed in conjunction with SERS to unravel the orientation of N-heterocyclic carbenes (NHC) adsorbed on noble-metal surfaces. (463) Besides DFT, molecular dynamics simulation also capable of elucidating SERS substrate-analyte interactions to support the feature importance ranking algorithm. For example, molecular dynamics simulations were employed to mimic the interactions between different bacteria species’ extracellular matrix (ECM) with a Raman molecule (4-mercaptopyridine) on the Au surface, thus rationale the redshifts identified by SERS spectra observation and HCA model. (432) Collectively, DFT and molecular dynamics thus exemplify the great potential of simulation to unravel the recognition mechanism, complement with ML algorithm to achieve excellent model interpretability and thus affirm accurate and robust ML-driven SERS frequency analysis. | ||||
Figure 24
Figure 24. Enhancing machine learning model interpretability. (a) Feature importance scores extracted from SHAP analysis for classification among SERS spectra of with high, medium, and low concentration of biomarker 2,3-DHBA. (b) Correlation between PCA score plot and PCA loading plot unravel the spectral changes induced by different types of interactions from different probe molecules. (c) Density function theory (DFT) simulation reveal ring complexation between APDS and SO2 to confirm the identified SERS spectral changes. Reprinted and adapted with permission from (a) ref (457), (b) ref (425), and (c) ref (426). Copyright 2021, American Chemical Society. Copyright 2024, Elsevier. Copyright 2022, Wiley.
The translation from manual to machine learning-driven SERS frequency shift analysis unlock SERS’s great potential by effectively utilize the entire spectra instead of focusing onto one/few specific peaks. Machine learning-driven analysis also enables large-scale data processing, which is crucial for biomedical application that requires a large number of samples and spectra to represent the population and account for the demographic variation such as age, gender, dietary habit, and medical history. However, one significant problem hampering the translation of ML-driven SERS into practical biomedical application is the lack of large, representative (typically tens of thousands to millions of spectra or samples) high-quality labeled data sets, which is crucial for training a robust machine learning model. In addition, differences in instruments and experimental conditions lead to the formation of “local” ML model that are optimized for specific setups with limited generalizability. Such models often perform well only within the context of their training conditions, which can adversely affect the accuracy when applied to data from different instruments or experimental setups. This can hinder reproducibility and collaboration, as results may not be consistent across different research groups or organizations. Hence, to accelerate the practical application of machine learning in SERS analysis, we envisage a need to develop a centralized SERS spectra libraries capable of unifying SERS spectra collected among different research groups. Such data unification, together with advances in instrumentation for platform fabrication and spectra acquisition, will fully realize the potential of ML in empowering SERS technology for biomedical applications.
6.2. SERS Denoising: Spectral and System Noises
Noise interference is hardly avoidable in Raman measurement, even with the introduction of advanced noise-reducing optoelectronic devices such as high-cooling CCD detectors and integrating spheres. (464) For instance, under the condition of either a pushed-to-the-limited acquisition time or a concentration at the limit of detection, the reduced signal intensity is normally accompanied by the increased noise, resulting in a reduced signal-to-noise ratio (SNR). (465) Accordingly, both the qualitative sensitivity and quantitative accuracy of Raman spectroscopy and the clarity of Raman imaging would be diminished. In recent years, advances in computer science have opened a new door with modern denoising algorithms that allow accurate identification and extraction of weak signals under low SNR conditions. (466−469) In this section, the relevant denoising algorithms are discussed from the aspect of the spectral data format, i.e., Raman spectrum (1D) and Raman imaging (3D).
6.2.1. Raman Spectrum (1D)
Both thermal noise and shot noise, the two most common types of noise in Raman measurement, are categorized as Gaussian white noise. This type of noise typically has a uniform power spectral density and follows a zero-centered Gaussian probability density function. (464) Consequently, denoising is either based on a frequency domain or a spatial domain. Frequency domain based denoising, such as Fourier transform filtering and wavelet denoising, capitalizes on the frequency disparities between signal and noise. (476) However, it is difficult to set a right threshold to exactly separate noise from the Raman signal, in which both sharp high-frequency and broad low-frequency peaks are involved. Spatial domain denoising, such as mean filtering and Savitzky-Golay (S-G) filtering, suppresses noise by processing each data point with the consideration of its neighbors. (477) Such averaging operation inevitably distorts peak information, resulting in a less fidelity of the denoised spectrum than that of the actual one. Recently, as shown in Figure 25a, Liu et al. developed a Peak Extraction and Retention (PEER) algorithm, which effectively addresses the loss of feature information in spatial domain denoising. With the integration of the peak detection algorithm and spatial domain denoising one, PEER maximizes the extraction and retention of peak information by adaptive denoising of segmented peaks with different SNR, ensuring high fidelity and high performance of the denoised Raman spectrum. (470)
Figure 25
Figure 25. Development of denoising strategies in Raman spectrum (1D) and Raman imaging (3D), from conventional signal processing algorithms to supervised and self-supervised deep learning ones. For spectral denoising: (a) PEER, a signal processing algorithm integrating peak extraction and retention, (470) (b) a supervised algorithm based on instrumental noise learning, (471) and (c) P2P, a zero-shot self-supervised spectral denoising algorithm. (472) For Raman imaging denoising: (d) a signal processing algorithm integrating Fourier transform denoising with imaging moving average filter, (473) (e) a two-stage supervised algorithm integrating both spectral and imaging processing, (474) and (f) S2S, a zero-shot self-supervised hyperspectral imaging denoising algorithm. (475)
The above denoising algorithms are derived from traditional chemometrics, which involves various parameters to be manually corrected. Differently, deep learning, highlighted by its exceptional ability to learn and represent data features, can adaptively extract signal characteristics from the noise, thereby effectively suppressing the noise. (478,479) By training a residual U-net based model on over 1.5 million experimental spectra with varying SNR, Bergholt et al. effectively realized denoising and reconstruction of low SNR Raman spectra. (480) Further, to reduce the reliance on massive experimental spectra, Shum et al. trained a generative adversarial network (GAN) on a data set containing tens of hundreds of experimental spectra, enabling construction of an extensive data set comprising tens of thousands of simulated spectra. The subsequently developed spectral preprocessing model (RSPSSL) demonstrated consistent and reliable denoising performance. (481) Note that data-driven deep learning models may suffer from limited generalizability. Specifically, the denoising is susceptible to potential serious distortion, once the application scenario exceeds the training domain of the model. To address this issue, Ren et al. developed an attention U-net (noise learning, NL) model to identify and remove instrumental noise, which is tailored to the Raman spectra from a single Raman instrument (Figure 25b). After being trained on over 100,000 instrumental noise spectra, the model notably enhanced the SNR of the output Raman spectrum from the specific Raman spectrometer, effectively transitioning deep learning from a sample-dependent approach to an instrument-dependent one. (471)
To overcome the massive data requirement of deep learning, as shown in Figure 25c, Liu et al. developed a self-supervised spectral denoising algorithm (Peak2Peak, P2P). (482) The P2P algorithm is derived from Noise2Noise (N2N), the most representative self-supervised 2D image denoising algorithm. N2N achieves self-supervised denoising by analyzing and extracting effective information from a large number of noisy images, which have the same subject but randomly distributed noise. (472) Alternatively, by combining data augmentation and a regularization function, P2P induces the deep learning model based on a simple convolutional neural network (CNN) to capture the spectral features under noise interference. The feature extraction capability of P2P is derived from self-supervised feature learning through data augmentation, while the denoising capability of P2P is derived from the combination of the loss function and regularization. Operating on a single noisy spectrum, P2P achieves exceptional spectral denoising with high performance and fidelity, significantly enhancing the efficiency of data mining and extending the scope of deep learning applications.
6.2.2. Raman Imaging (3D)
The aforementioned denoising algorithms can also be applied for Raman imaging, regarding the noise presented in Raman imaging is primarily derived from the spectral acquisition process. For example, Shum et al. used the RSPSSL model to improve the SNR of Raman imaging of cancer tissue, thereby effectively reducing the acquisition time by almost ten times. (481) Ren et al. significantly improved the spatial resolution of TERS imaging with the aid of NL model. (471)
However, spectral denoising algorithms neglected the image feature of hyperspectral (3D) data, resulting in inadequate data exploitation. Therefore, both spectral (1D) and image (2D) denoising algorithms are combined to improve denoising performance. For example, Liu et al. sequentially used the Fast Fourier Transform (FFT) filtering and the moving average filtering for spectral and image denoising, respectively (Figure 25d). The overall denoising significantly improved the clarity of image boundaries and detailed features in Raman imaging. (473) The similar performance was also demonstrated by Shum et al. using deep learning algorithm, in which 1D and 2D residual U-net convolutional neural networks are for denoising spectrum and images, respectively (Figure 25e). (474)
Further, aiming at self-supervised denoising, as shown in Figure 25f, Liu et al. developed a hyperspectral denoising algorithm (Signal2Signal, S2S) derived from P2P. By integrating hyperspectral undersampling and U-net, S2S could improve the clarity and spatial resolution by more than three times, even for a Raman image with a spectral SNR as low as 1.12. The robust detection of target signals and the wide-ranging applicability of S2S not only enhance the temporal resolution of Raman imaging, but also show the potential for real-time denoising during Raman imaging process. (475)
In summary, deep learning significantly bolsters the capability of denoising algorithms in identifying and extracting weak signals. Furthermore, self-supervised deep learning adeptly mitigates the dependence on massive labeled data. This not only substantially reduces the technical barriers to deploying these algorithms but also enhances their versatility and practical applicability.
6.3. SERS Spectral Unmixing: From Chemometrics to Deep Learning
Unmixing various molecular components (endmembers) with the underlying fractions (abundances) in biological samples from SERS spectra is an emerging topic and is increasingly attractive in biomedical applications. Generally, inversely retrieving the SERS spectra of pure substances is challenging. (483−485) In addition to comprehensive understanding of the spectral signals themselves, taking into account the underlying characteristics of biological samples and experimental methods used also benefits spectral unmixing with higher accuracy. For the case of lacking detailed information about the biological samples, methods such as N-FINDR and Multivariate Curve Resolution (MCR) can be employed to directly extract potential components and endmembers from the scene. (486,487) However, such direct decomposition approaches are intrinsically less reliable especially for biomedical applications, which require further experimental evidence to validate the sources of the decomposed spectra. With some contributing components of the spectra available, spectral analysis becomes less complex and more convincing. In other words, full knowledge of the analytes would yield promising unmixing results. Sometimes not all molecular components within samples can be detected by the SERS signal, which is attributed to plasmonic surface science. (488−490) It suggests that a deeper understanding of the interaction between molecules and the substrate helps narrow down the range of potential molecules. In this case, less is more─narrowing the range of signal sources can aid in a deeper analysis of molecular quantity information. Most unmixing algorithms approximated the mixed spectra as a linear combination of individual components. (491,492) When pure substance spectra are available, methods such as non-negative least-squares (NNLS) can be used to decompose the mixed spectra and the corresponding coefficients serve as the basis for relative quantification. (493,494) However, the real situation cannot be limited to linear relationships, which has attracted increasing concerns. (495,496) Considering the interactions between molecules, as well as those between molecules and the substrate in complex systems, more complicated models need to be established. (497−499) Furthermore, molecular spectra may vary under different measurement conditions, and additional factors may reduce the accuracy of unmixing results. (500,501)
Unlike traditional chemometrics, which often relies on linear methods, deep learning enables nonlinear spectral unmixing by extracting high-level features from spectral data, followed by the estimation of endmembers and their abundances. The main network architecture employed for this purpose is the autoencoder composed of an encoder and a decoder. Typically, the encoder maps the spectral data to abundance values, which are then reconstructed back to the spectrum by the decoder as endmembers. (502,503) Georgiev et al. and Su et al. further improved the physical interpretability of autoencoders by introducing a non-negativity constraint for the endmembers and a sum-to-one constraint for the abundances. (504,505) Experiments with both synthetic and biological data sets demonstrated that this constrained autoencoder approach produced more accurate endmember and abundance estimates than conventional unmixing methods. Apart from autoencoders, lots of relevant efforts in hyperspectral unmixing have pointed out alternative architectures exhibits the potential of competitive endmember/abundance estimation for SERS, including CNNs, (506) U-Net, (507) Transformer, (508) and unsupervised learning. (509) We believe developing advanced deep learning-based unmixing methods integrated with the properties of biological samples and experimental design will further boost the deployment of SERS technology in biomedical applications.
7. SERS Quantification: Emerging Techniques
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Following the first discovery of SERS-enabled single-molecule detection, (8,9) floods of works have revealed the detectability of multiple analytes in ultralow concentrations (down to femtomolar or even attomolar level (510−512)) by various kinds of SERS substrates, even simply by the conventional Ag nanospheres. (513,514) The bianalyte SERS technique proposed by Le Ru et al. (515) has been widely used as a statistic proof of the single-molecule sensitivity of the SERS substrate. Nevertheless, the cons come along with the pros that the ultrasensitive electromagnetic hotspots are highly localized and heterogeneous from each other due to the atom-level variations beyond control (516,517) (Figure 26a). Therefore, a slight difference in the adsorption site and orientation of an analyte molecule on the substrate may cause a relatively large SERS signal fluctuation, causing irreproducible intensity-based quantification. (518)
Figure 26
Figure 26. Emerging techniques for SERS quantification. (a) Different factors causing SERS intensity fluctuations including different electromagnetic enhancement due to variable distance between the analyte and the substrate surface (i, ii) and variable adsorption site (i, iii), different adsorption orientations (iv), atomic mobilization (v), NP aggregation (vi), and heterogeneous substrate morphology (vii). (b) Signal calibration by the internal standard. The signal intensity of the analytes can be interfered by a lot of uncontrollable factors while the ratio of analyte signal to internal standard signal can correct these variations, realizing more robust quantification. Three typical strategies of internal standards: (c) co-adsorption of the internal standard molecules with the analytes on the SERS substrate and (d) embedment of the internal standard molecules in the core–shell NP and sensing of the analytes on the outer layer via direct adsorption, specific capturing or analyte-induced chemical change of the surface functionalized molecules. (e) Intrinsic internal standards originated from the substrate and the solvent. (f) The concept of digital colloid-enhanced Raman spectroscopy by single-molecule counting. (g) Dual-mode SERS and electrochemical detection of miRNA. Adapted from ref (523).
Given reproducibility is the premise of any real-world application, (519) primary efforts have been put into advancing the SERS substrate toward ever-higher uniformity. For example, lithography technique, only widely applied in the recent dozens of years, is well acknowledged to produce highly repeatable arrays. (375) Nevertheless, the hotspots are still heterogeneous within one substrate and across different substrates and the difference is unable to be corrected due to the irreversible molecular capture on dried substrates. While for wet chemistry, the uniformity across NPs is much more difficult to control. Though surfactant may enhance the mediation of surface morphology to some extent, (520,521) the surface accessibility to analytes could be largely deteriorated. (522) In this sense, emerging technical routes have been explored to improve the quantitative reproducibility toward reliable and usable SERS.
7.1. Internal Standards SERS Nanoparticles
The analog intensities, generally used for the quantification of relatively higher concentrations, are vulnerable to the variables including hotspot enhancement factor, substrate-molecule interaction and instrumental differences. Internal standard (IS) is a calibration methodology that has been long practiced in analytical chemistry far beyond SERS to correct the signal fluctuations out of manual control. (524) For the effectiveness of calibration, the IS chemical should be carefully selected to compensate all the variables (β) involved in the quantification except the concentration (C), i.e., In this sense, given the IS concentration (CIS) is predetermined, i.e., fIS(CIS) is a constant value, the analyte concentration (Ca) can be reliably deducted from analyte signal intensity (Ia) based on a pre-established reflection without the above-mentioned interfering factors after being corrected by the IS signal (IIS) (Figure 26b).
(1)
(2)
Isotopically edited counterpart of the analyte molecules has been usually used as the IS in regard to the distinguishable vibrational signatures and comparable chemical and physical properties as the analytes including the affinity to the SERS substrates and Rama cross-section (525) (Figure 26c). This may guarantee the optimal correction of the variables that the analyte molecule encounters with distinguishable IS signals. (526) Conceptual validation has been primarily explored with some classical fluorescence dyes such as rhodamine 6G (R6G-d0), rhodamine B (RhB-d0), nile blue (NB-d0) and crystal violet (CV-d0), with their isotopically edited counterparts as the IS, e.g., R6G-d6/d2, RhB-d2, NB-d2, and CV-d6, respectively. (525,527) Apart from the hydrogen atom, isotopic editing has also been implemented on the carbon atom and the nitrogen atom such as mononucleotide (e.g., 2′-deoxyadenosine-13C10,15N5-monophosphate) (528) and 13C caffeine. (529) Though the absolute localized enhancement factor is not easy to be corrected, the IS has presented superiority in correcting the enhancement factor across different probe volumes, substrate batches and measurement conditions in the collective sense via random coadsorption on the electromagnetic hotspots with the analytes. (525,529) This leads to minimized signal fluctuations within one sample, across different samples and over time for enhanced quantitative repeatability. In biosamples with abundant uncertainties varying the detection capability, IS should be particularly utilized to reliably unveil the biological process, such as the research on the toxicokinetic behavior of paraquat in plasma and lung tissues (IS: paraquat-d8). (530) While for real applications, the isotopically edited counterparts are not easy or not cheap to obtain, a more generalizable alternative can be using the chemicals with similar structures for optimally comparable molecular properties. For example, metformin hydrochloride was used as the IS for phenformin hydrochloride and streptomycin sulfate was used for tigecycline to increase the linearity of SERS detection. (531)
Label-free strategy has been long suffered from the competitive adsorption, so is the situation between the analyte and the corresponding IS chemical, leading to uncertain effective IS concentration, Therefore, a more stable binding of IS molecules on the SERS substrate and the protection of the IS molecules from the background conditions have been paid specific attention to in the design of the plasmonic sensor. (532) The most widely applied strategy is to use the Raman reporters with thiol moiety embedded in the gap of a core–shell structured NP (Figure 26d). In this way, the concentration of the IS molecules is primarily maintained constant. For instance, 4-aminothiophenol was embedded in the interface of Au core@Ag shell NP as the IS, thereafter the reduced signal of methylene blue caused by the competitive adsorption of okadaic acid on the aptamer was corrected by the IS signal for anti-interfering and selective detection of okadaic acid in real food and environmental samples. (533) Similarly, reported by Jiang and co-workers, 1,4-benzenedithiol, embedded Au core@Ag shell NPs, was also used as the IS for the detection of H2O2 and cholesterol inside living cells at single-cell level. (534) In addition, reporter molecules with alkyne and nitrile groups are extremely preferred for the detection in biosamples for their unique signatures in Raman silent region (1800–2800 cm–1) so that the IS signals can be extracted with high confidence from the background signals. (535) Mei et al. reported using 4-mercaptobenzonitrile as the IS to detect a representative bacterial metabolite, pyocyanin, released in skin interstitial fluid for wound infection diagnosis. (536) The identical IS embedded in the gap of Au core–shell nanoflower has also been applied to calibrate the signal change caused by the reduction of 4-nitrothiophenol functionalized on the outer Au shell to 4-aminothiophenol related to the endogenous and exogenous H2S in living cells. (223)
Another kind of IS strategy is to use the intrinsic signals originated from the substrates and the solvents which can free the researches from extra labor in IS functionalization (Figure 26e). These intrinsic IS signals have also been proved elite in calibrating the heterogeneous hotspots as well as batch-to-batch and instrumental variations. Graphene, with a second-order 2D peak at about 2655 cm–1 in the silent region, is suitable to be selected as the IS chemical. In the meanwhile, the decoration of graphite on the NPs and dry substrates can enhance the uniformity and stability. (537,538) Other chemicals introduced in the substrate fabrication for large-scale substrate uniformity (e.g., poly(4-vinylpyridine) (539)) and organic solvents (e.g., ethanol, (540) acetone (541) and dichloromethane (542)) can also be utilized as the IS chemicals. Besides, plasmon-enhanced electronic Raman scattering, reflecting the electromagnetic fields at the identical spot, has also been applied to calibrate the analyte Raman scattering signals in a temporal and spatial manner. (543)
Though there are abundant variables in SERS measurements to cause nonrepeatable quantification, IS protocol has not yet generally practiced in all the quantitative biomedical applications to date. As mentioned above, IS calibration should be promoted especially in biosamples for reliable quantification and the IS chemicals must be carefully selected toward the most confidently discriminable IS signatures and the least spectral overlapping with the analyte-originated signatures. IS stability in effective concentration and properties are also essential for reliable calibration given the varied background conditions and target analyte concentration.
7.2. Digital SERS (dSERS)
While for relatively high analyte concentrations, the random fluctuation of analog intensity may be averaged out upon a wealth of analyte-hotspot interactions in the probe volume after IS calibration, as the lowering concentration, SERS single-molecule intensity fluctuations (SIFs) become increasingly prominent. Therefore, many efforts have been applied on the spectral analysis, particularly, focused on statistical patterns of the spectra rather than individual intensities. As the signal intensity distribution changes from a Gaussian-like to a long-tail pattern as the analyte concentration decreases, (9,544) the parameters derived from the exponentially modified Gaussian distribution (545) and the truncated Pareto mixture distribution (544) have been explored for the quantification of low concentrations. However, the number of noise spectra may eventually overwhelm the number of signal spectra as the lowering concentration, making it difficult to obtain a robust distribution for analyte quantification upon limited spectral number in the practical sense. (515) Therefore, the SIFs are picked out and analyzed for their frequency. To this regard, the fundamental hypothesis is that the probability of single-molecule events should correlate with the analyte concentration even if the concentration is quite low. Herein, fast Fourier transform (FFT) is a mathematic method commonly used to represent frequency. Brulé and co-workers computed the cutoff frequency between the white noise (the noise spectra) and the pink noise (the bright single-molecule events) after FFT of the spectral signals, which showed a Freundlich isotherm with the analyte concentration. (546) Toward a “standardization” process of SERS protocols, statistics including the root mean squared error of prediction, the standard error of performance, bias, etc. have also been suggested to evaluate the reproducibility and trueness of a quantitative SERS method in the interlab scale with regard to distinctive instrumentations, SERS substrates and manual operations. (547)
Digital protocol was first proposed by de Albuquerque et al. to address the signal fluctuations at low concentrations as the scarce probability of a detectable single molecule and the variable single-molecule signal intensity. (548) Apparently, the analog-to-digital conversion can largely spare the quantitative statistics from analog intensity variations since only binary digit (positive or negative state) is given attention. In this work, they prepared the dried liquid sample on a self-assembled Au substrate and demonstrated the limit of quantification of enrofloxacin and ciprofloxacin down to 2.8 pM by counting the positive spectra acquired on the substrate. Technical follow-ups of the digital protocol have been explored using different SERS substrates and for various analytes. (549−552)
While the obstacles inherent to dried substrates may still deviate the detected concentration from the original analyte concentration in the sample, so it is impossible to preestablish a calibration curve usable in subsequent applications. To reduce the digital concept to practice, Bi and co-workers proposed a colloid-based single-molecule detection approach, i.e., digital colloid-enhanced Raman spectroscopy (dCERS) (16) (Figure 26f). In the colloidal system with both hotspots and target analytes randomly and statistically uniform-distributed in the probe-volume level, single-molecule events follow the Poisson distribution. Therefore, desired reproducibility and measurement accuracy can be achieved at ultralow concentrations under the practical demands on accuracy and time efficiency as it is largely determined by the accumulated single-molecule counts 3. (N: the number of detected single-molecule events)
(3)
Digital SERS is actually a tool for efficient spectral analysis with a uniquely statistical perspective to interpret the SERS signals. Analytes at ultralow concentrations can be thereby not only identified but also reliably quantified, propelling SERS toward real-world applications. A range of molecules including proteins, nucleic acids and metabolites has been successfully quantified using digital SERS as long as with identifiable SERS signatures and adequate interaction with the SERS substrates. Actually, this can be further modified according to a specific purpose as long as a calibration curve can be preestablished for a certain analyte and a certain kind of SERS substrates. For real applicational scenarios involving more complicated background matrix and competitive adsorption for the hotspots, comprehensive sensing platform should be developed, incorporating digital SERS for spectral analysis and other pretreatment modules to reduce the interference factors and improve the detection efficiency of the target analytes. (553−556)
7.3. Dual Modality SERS Sensing
Quantification in SERS can benefit from integrating different sensing modalities during detection, an approach needed to improve sensitivity and selectivity and to overcome the impossibility of introducing an internal standard in the measurement, as, in some instances, their use is not possible or not practical. This is why, rather than foregoing the use of SERS as transduction modality, dual modality sensing can be leveraged instead. There are various transduction modalities that can be integrated with SERS in dual modality sensing, spanning from colorimetric detection (557) to photoacoustic imaging. (558) Several of these approaches find application in diagnostics and medical imaging, (559) and it is safe to say that their continued implementation and optimization is motivated by the rapid growth of SERS sensing in clinical diagnostics. However, dual modality SERS sensors most often integrate electrochemistry (560) and fluorescence, (561) likely because of the fundamental overlap among SERS and these techniques.
The SERS effect was first discovered and explained for systems in which a Ag electrode was also acting as the SERS substrate (1,562) and, likely because of this reason, it has been straightforward to envision the integration of electrochemistry (EC) and SERS. However, only recently electrochemical SERS (EC-SERS) has become mainstream, (563) with applications in biosensing, catalysis, and environmental analysis. EC-SERS is generally used to boost the sensitivity of SERS sensing, owing to the fact that analyte-metal interactions at the nanostructured electrode surface can be enhanced in the presence of an applied voltage, thus boosting the limit of detection. Nonetheless, for this approach to work, several constraints need to be taken into account. (564) First of all, one should consider the cleanliness of the nanostructured surface, which also implies the need to remove surface passivating agents in the instances in which the electrode has been fabricated by substrate deposition of colloidal NPs, as the presence of these materials can introduce spurious signals and increase nonfaradaic contributions. Second, the electrolyte properties need to be considered, as these molecules may interfere with the analyte and alter the local ionic strength of the system, thus affecting the SERS response. Furthermore, the laser excitation can locally alter the redox properties of the analytes depending on the wavelength used, thus affecting the electrochemical response. However, this effect, if properly understood and characterized for each analyte, could improve selectivity in multiplexed EC-SERS sensing. Despite these caveats, EC-SERS has found increasing applicability, with a substantial growth in applications covering the detection of disease biomarkers, (565) with combined equipment already on the market. (566) For instance, Zhou et al. have designed a combined EC-SERS sensor based on toehold-mediated amplification to detect miRNAs with LODs of 2.2 and 0.12 fM for the EC and SERS modalities, respectively, also in cancer cells (Figure 26g). (523)
However, an interesting approach in EC-SERS stems from the opportunity to leverage the EC modality to quantify the surface area of the nanostructured sensor surface. This approach is extremely important in terms of analyte quantification in the absence of an internal standard, as the effective surface area of the sensor is a relevant parameter for analyte concentration calculation in SERS, for which however an exact determination is often impossible, especially in the case of nanoscale roughness. Sardar et al. leveraged EC-SERS to increase accuracy in SERS quantification by fabricating a series of SERS substrates constituted by screen printed electrodes (SPEs) with increasing amounts of deposited Au NPs and characterizing them electrochemically with cyclic voltammetry (CV) and chronocoulometry. (567) This initial step was then followed by deposition of increasing concentrations of Raman-active aminothiophenol (ATP) and SERS analysis. By combining the two methods, they were able to correlate the substrate charge (measured by EC) to the ATP signal intensity (measured by SERS) with tight root mean squared error (RMSE) variations, thus confirming the power of the dual modality method in improving quantification accuracy enabled by the introduction of controlled signal diversity in the system.
Dual modality fluorescence-SERS detection is, in addition to EC-SERS, the most studied and leveraged sensing method. Likely because fluorescence/SERS modulation can be achieved by varying the distance from the metallic surface of a molecule that is fluorescent and Raman active, (568) both direct and indirect SERS sensing methods can be envisioned. Dardir et al. developed an ON/OFF indirect SERS sensor comprising Au nanostars and fluorescently labeled DNA strands to recognize influenza A (IAV) viral RNA both in buffer and intracellularly, even at the single particle level. (569) In this approach, the fluorophore, bound to the 3′ end of the surface-functionalized DNA, is brought in proximity to the metal, or away from it, depending on whether the viral RNA is present or not, with a consequent ON/OFF signal in the SERS response. At the same time, the corresponding fluorescence signal is turned OFF/ON, enabling detection not only by means of SERS but also, complementarily, by fluorescence imaging, providing both robustness and sensitivity to mutations. By slight modifications to the nanostar-bound DNA sequence, the method can be envisioned to be responsive primarily to fluorescence (with ON signal in the presence of viral RNA) for seamless introduction to virology laboratories, similar to what can be done with nanoflare-based detection. (570) SERS-tag design can also be leveraged to enable both fluorescence and SERS transduction without real-time modulation of distance-dependent SERS and fluorescence signals. For instance, Bhamidipati et al. showed that the combination of SERS and fluorescence can enable quantification and spatial localization of prostate specific membrane antigen (PSMA) molecules on cells and tissues of prostate cancer patients (571) and improve patient stratification, compared to immunohistochemistry or histopathology alone. (572)
8. Surface-Enhanced Raman Scattering in Biomedicine
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8.1. Nucleic Acid Multiplexing SERS Detection
Nucleic acids are the carriers of genetic information and play significant roles in cellular processes, such as cell division and protein synthesis. Abnormalities in nucleic acids and their modification levels have been proven to be closely related to diseases such as cancer. The development of analytical methods for nucleic acid detection has become a major focus of research in life sciences. Currently, the most common methods for nucleic acid detection include quantitative polymerase chain reaction (PCR), digital PCR, and next-generation sequencing (NGS). While highly accurate, these fluorescence-based methods present challenges for multiplex detection, and NGS-based approaches require long turnaround times (3–4 h) and expensive specialized equipment. SERS is emerging as a new tool for nucleic acid detection, offering the advantages of ultrahigh sensitivity and multiplexing capability. In this section, we will review recent progress in SERS-based multiplex detection of nucleic acid markers, such as microRNAs (miRNAs), (573−576) gene mutations, (577) fusion genes, (578) and viral RNA. (579)
In 2020, Si et al. developed a SERS sensor array for the spatially multiplexed detection of four cancer-associated microRNAs (miR-1246, miR-221, miR-133a, and miR-21). (573) To achieve highly sensitive detection, they integrated SERS with a nonenzymatic DNA cycle amplification strategy known as the catalytic hairpin self-assembly (CHA) reaction. The sensor array, consisting of four different sensing units, was constructed by immobilizing hairpin DNA 1 (HP1) onto Au/Ag alloy NP-coated detection wells. For each target miRNA, specific SERS nanotags were prepared by modifying Au/Ag alloy NPs with Raman reporter molecules and HP2. The presence of target miRNAs initiated the CHA reaction, where the hybridization between HP1 and the target miRNA exposed a hidden toehold in the HP1 stem, allowing it to hybridize with the HP2-functionalized SERS nanotags. This process successfully anchored the SERS nanotags onto the sensor array and released the target miRNA for the next cycle of detection. This strategy enabled the detection of the four target miRNAs in cellular RNA extracts with a detection limit of 0.15 pM. However, the entire process took over 4 h and was not capable of detecting all four miRNAs simultaneously in a single sample.
To reduce assay turnaround time, a lateral flow assay (LFA)-based SERS sensor was combined with CHA for detecting lung cancer-related miRNA biomarkers. (574) SERS nanotags were functionalized with biotinylated HP1 (biotin-HP1), monoclonal antibodies, and Raman reporters. The system was designed with two test lines, each fixed with a different HP2 sequence, enabling spatially duplex detection of miR-196a-5p and miR-31–5p. When the SERS nanotags passed through the conjugate pad, the CHA reaction was initiated by the target miRNAs, which hybridized with biotin-HP1, exposing biotin molecules. As the solution flowed along the strip to the nitrocellulose membrane, the CHA reaction continued, activated by the HP2 sequences fixed on the test lines. This reaction led to the self-assembly of the two HP 2s, releasing the miRNA for subsequent cycles. The SERS nanotags with exposed biotin molecules were then captured by streptavidin-modified test lines, where the accumulation of nanotags created numerous “hotspots” that amplified the SERS signals, enabling detection down to the nanomolar level. Excess SERS nanotags were captured by a control line coated with antihuman IgG. The CHA-assisted SERS-LFA assay was further validated with real serum samples from 30 healthy donors and 120 lung cancer patients across stages I to IV, revealing increasing levels of both miRNA biomarkers with advancing stages. The results closely matched those from the standard quantitative reverse transcription-PCR (qRT-PCR) assay, with relative errors below 5%. Additionally, the entire process took only 40 min, highlighting its potential for clinical applications. Building on this work, Mao et al. from the same research group improved the assay’s efficiency, enabling the detection of dual miRNAs on a single test line and reducing the assay time to 30 min (Figure 27a). (575) This was achieved by immobilizing two different HP2 sequences on a single test line. The use of Au nanocages as SERS nanotag substrates further enhanced detection sensitivity, achieving limits of detection as low as 3.31 pM for miR-21 and 2.18 pM for miR-196a-5p in human urine. The accuracy of the method was confirmed through comparison with the qRT-PCR assay, with relative errors around 3%.
Figure 27
Figure 27. Multiplex SERS detection of nucleic acids. (a) An LFA-SERS sensor combined with CHA for multiplex detection of miRNAs on a single test line. Adapted from ref (575). (b) Magnetic pull-down of target miRNAs for multiplex SERS labeling, forming core–satellite complexes in the presence of target miRNAs. Adapted from ref (576). (c) Identification of nucleic acid targets using acetylene-tagged Hoechst molecules binding to DNA-tethered Au NPs. Adatped from ref (578). (d) Locker probes-assisted RPA combined with proximity-programmed SERS nanotags for the detection of fusion genes. Adapted from ref (582).
Alternatively, SERS detection can be combined with magnetic separation for nucleic acid detection. Lyu et al. developed a magnetic pull-down assisted PCR/SERS assay for the multiplex detection of circulating tumor DNA (ctDNA) mutations in the plasma of colorectal cancer patients. (577) This assay was designed using allele-specific PCR to amplify common colorectal cancer mutant targets, followed by magnetic pull-down of the PCR amplicons. The mutant targets were then identified using SERS nanotags, and the SERS signals were read out for analysis. The PCR/SERS strategy demonstrated high specificity and sensitivity in detecting plasma ctDNA, even with as low as 1% mutant alleles in a background of abundant wild-type cell-free DNA. The results from the PCR/SERS assay were consistent with those obtained using digital PCR in the analysis of nine plasma samples. However, the PCR/SERS assay offered the added advantages of a single-tube multiplex format and reduced assay time compared to digital PCR, making it a more convenient option for ctDNA analysis.
Given the exceptionally strong signals emitted by anisotropic SERS nanotags, Wu et al. proposed a PCR-free SERS assay utilizing anisotropic SERS nanotags for the detection of miRNAs (Figure 27b). (576) Ag-coated magnetic NPs and SERS nanotags were conjugated with capture and detection DNA probes that were partially complementary to target miRNAs. The presence of the target miRNAs initiated the formation of core–satellite complexes, which led to significantly enhanced SERS signals following magnetic separation. This method allowed for the simultaneous detection of three miRNA biomarkers─miR-21, miR-122, and miR-223─with detection limits of 311, 349, and 374 aM, respectively. The researchers applied this method to serum samples from 92 hepatocellular carcinoma (HCC) patients and observed that miR-21 levels decreased while miR-122 and miR-223 levels increased in 11 patients after hepatectomy. Additionally, the assay was used to detect miRNAs in α-fetoprotein-negative patients (n = 14) and in patients at various stages of barcelona clinic liver cancer (BCLC). A similar approach has been utilized for the multiplex detection of exosomal miRNAs. (580) Despite its promise for clinical translation, the entire process required more than 4 h, indicating a need for further optimization to reduce the assay time.
Unlike above the two-step hybridization methods, Xu et al. developed a more rapid and efficient approach by incorporating a magnetic pull-down SERS assay with duplex-specific nuclease (DSN)-mediated signal amplification for the multiplex detection of miRNAs (miR-21, miR-155, and let-7b). (581) This method involved synthesizing complexes of magnetic NPs functionalized with capture DNA probes and SERS nanotags. When a target miRNA was introduced, it specifically hybridized with the capture DNA probe to form DNA/miRNA heteroduplexes. These heteroduplexes were then selectively hydrolyzed by DSN, leading to the release of SERS nanotags from the magnetic NPs, which caused a subsequent reduction in the SERS signal after magnetic separation. Remarkably, the entire process took only 40 min. This method was validated using cell line samples and simulated human samples, demonstrating recovery rates ranging from 97.1% to 106.4%, highlighting its potential for rapid and accurate miRNA detection.
It is important to note that the use of NPs can sometimes lead to false-positive results, particularly at low target concentrations. To address this issue, Jang et al. developed a nucleic acid multiplexing platform that avoids the use of SERS nanotags. (579) This method involves the magnetic separation of target genes, followed by labeling with fluorophore-tagged DNA probes. The signal probes were then either released by raising the temperature of the magnetic particle solution for fluorescence detection or mixed with SERS-active substrates for signal readouts. The SERS-based detection achieved sensitivity ranging from 10 aM to 1 pM of synthetic genes, depending on the types of SERS-active substrates used. As an alternative to thermal release, strand displacement was incorporated with SERS strategies (Figure 27c). (578) In this system, acetylene-tagged Hoechst molecules were used as Raman probes that bind to their corresponding DNA sequence tethered on Au NPs. When the target nucleic acids hybridized with the complementary strand on the Au NPs, the Raman probes dissociated from the particles, leading to a decrease in signal intensity. This system has been successfully demonstrated in the identification of cellular miRNAs.
Zeng et al. introduced an innovative method to minimize nonspecific “noise” signals caused by excessive wild-type background sequences, particularly in rapid isothermal multiplex target amplification scenarios. (582) They combined locker probes with a “proximity-programmed” SERS readout for the multiplex detection of cancer gene fusion nucleic acid variants (Figure 27d). Locker probes are synthetic nucleic acid bases that feature methylene linkages between the 2′-oxygen and 4′-carbon groups of ribose, providing greater thermal stability than conventional Watson–Crick base pairs. These probes have a higher affinity for wild-type sequences, which helps in enriching mutant variants during multiplex recombinase polymerase amplification (RPA). The “proximity-programmed” SERS readout allowed precise control over plasmonic signaling based on hybridization, enabling the specific detection of multiple target amplicons within a single reaction. This approach effectively reduces nonspecific signals and improves the accuracy of multiplex nucleic acid detection.
The SERS-based multiplex detection of nucleic acids thus represents a significant advancement in molecular diagnostics, offering unparalleled sensitivity and specificity for the simultaneous analysis of multiple targets. These technologies hold great potential for applications in areas such as infectious disease diagnostics, genetic screening, and personalized medicine. However, to fully realize their clinical potential, further developments are needed to address challenges related to reproducibility, signal uniformity, and the complexity of assay protocols. The integration of SERS with automated microfluidic systems and the development of novel plasmonic nanostructures are likely to enhance assay performance, making SERS a more practical and scalable solution for routine clinical use. The continued refinement of these approaches is expected to broaden the utility of SERS-based nucleic acid detection, paving the way for more accurate, rapid, and accessible diagnostic tools in healthcare.
8.2. Protein Structure Characterization and Function Exploration
Proteins are structural and functional unit of the cell, made of amino acids that connected by peptide bonds. Raman spectroscopy can provide structural information on proteins including vibrations from amide (I and III), amino acid residues (Phe, Trp, Tyr, etc.) and protein cofactors (heme, flavin, etc.). (583,584) Resonance Raman scattering of protein cofactors can be induced by optimization of laser excitation, which combined with SERS (known as SERRS) allows for selectively collecting SERRS signals of proteins in biological complexes. (585) Intrinsic protein fingerprints can be obtained by SERS either directly or indirectly with protein ligands. SERS-based studies on proteins have widespread applications in biology and biomedicine including exploration of protein structure–function relationships, protein biomarker sensing, tumor targeting and evaluation of antitumor treatment.
Direct contact proteins with noble metals might cause protein denaturation, resulting in protein unfolding or conformation change. (586) On the other hand, coating noble metals (Ag and Au) with biocompatible materials (silica, chitosan, alkanethiol, etc.) is helpful to protect protein native structures. (587) Alternatively, semiconducting SERS-active materials like titanium dioxides are found to display remarkably better biocompatibility than noble metals and photoinduced electron transfer might occur at the semiconducting material-protein interface. (165,588) Additionally, nickel is a promising SERS-active material for proteins and it has been proven to be capable of specifically offering electrons to the redox proteins like cytochrome c (Cyt c) and Cytochrome b5, facilitating in situ investigation of redox protein electron transfer and their dynamics. (589)
Cyt c release from the mitochondria is a crucial event during the early stages of apoptosis, and SERRS has been exploited to probing Cyt c release. Nickel nanowires were used for rapid Cyt c reduction and determination of the redox states of Cyt c released from mitochondria in apoptotic HeLa cells. With the aid of Ag NPs, label-free and highly sensitive Cyt c quantification is achieved by SERRS. (590) The Cyt c–cardiolipin interaction is involved in alteration of mitochondrial membrane permeability at the early phase of apoptosis before Cyt c release from mitochondria. (591) The structural change of cardiolipin-bound Cyt c and its correlation with mitochondrial Cyt c release were explored through SERRS. (592) Herein, in situ monitoring Cyt c release from isolated mitochondria can be achieved on a nanostructured nickel film, according to which the molecular mechanism underlying Cyt c redox-controlled membrane permeability was revealed. Furthermore, Ag NPs coated with nickel shells are found useful for in situ probing of reactive oxygen species (ROS) formation from microsomal monooxygenase. Remarkably, label-free evaluation of an antitumor drug-induced apoptosis was achieved by SERRS-based monitoring of Cyt c release in living cells. (593)
SERS can probe secondary structure information on membrane-attached proteins and investigate protein–membrane interactions. Membrane-associated proteins can be characterized after immobilization on lipid-modified SERS-active supports or indirectly detected by SERS nanotags modified with protein specific antibodies, receptors or aptamers. (594,595) Phospholipid bilayers can be coated on metal supports through electrostatic interactions and other weak interactions. (596) Alkanethiol molecules are usually used to improve the stability of the lipid membranes, and they are attached onto metals through metal-S covalent bonds as a first layer, followed by self-assembly of a second layer of phospholipids. (596) Alternatively, it is also feasible for phospholipid bilayers to be covalently assembled on to semiconducting materials like TiO2 NPs. (597) Immobilization of reduced Cytochrome b5 at Iipid bilayer-coated Ag NPs has recently been achieved and electron transfer between reduced Cyt b5 and oxidized Cyt c or myoglobin was monitored by SERRS in real time. Lipid bilayer-coated SERS-active materials provide a sensitive platform for membrane protein analysis and sensing, and pave the way for in situ exploration of protein structural basis and functions. (596)
Large proteins generally consist of several distinct protein domains, and random orientation of different domains would result in poor SERS spectral reproducibility, especially for nonconjugated proteins. Biocompatible immobilization and controlled orientation are both important for protein function exploration on SERS-active substrates. To this end, spacer molecules linking proteins and SERS substrates were designed and optimized, balancing biocompatibility and Raman scattering enhancement. Then the spacer molecule-modified Ag films were used for capturing His-tagged proteins via nickel-imidazole coordination, by which controlled protein orientation and reproducible SERS spectra were obtained. This strategy enables label-free protein function exploration as evidenced by two model systems of protein–protein and protein-drug interactions. This study is crucially important for understanding the structural basis of protein functional versatility and will contribute to the fields of drug design screening. (598)
8.3. Modeling and Prediction of Protein Molecular Species
AlphaFold3 has revolutionized the field of structural biology, potentially rendering traditional protein structure prediction methods like X-ray crystallography, NMR spectroscopy, and cryo-electron microscopy. (599) While these conventional techniques provide static snapshots of protein conformations, incisive experimental approaches are still required to unveil the trajectory of protein conformational changes. In this regard, SERS has its unique merit to achieve in situ and dynamic characterization of proteins in the physiological environment. It is expected that abundant intrinsic fingerprint information provided by SERS can be used for scrutinizing the structure of proteins, as the secondary structural details can be derived from Raman spectra. To decipher the spectrum to extract the protein’s structure, i.e., to establish a spectrum-structure correlation, efficient and accurate simulation of SER spectra is crucial. Despite considerable effort to developing advanced methods for interpreting and predicting SER spectra, achieving a well-defined spectrum-structure correlation remains challenging. The primary difficulty lies not only in accurately describing the complex experimental environment surrounding proteins but also in balancing calculation accuracy with the computational efficiency of theoretical models. Although proteins possess tertiary structures, their stability and controllability are low, and their large molecular weight and dynamic conformations present significant challenges for simulating protein Raman spectra. In this aspect, such challenge is even more pronounced in SERS, as it involves not only the polarizability changes of proteins (Raman spectroscopy) but also their interactions with the surface (nanosurface science) and the localized electromagnetic field (nanoplasmonics), as illustrated in Figure 28a. To be specific, different orientations of proteins interacting with SERS substrates lead to varying conformations and surface-induced denaturation. In addition, the hotspots where proteins stay is a gradient surface-enhanced electric field. As a result, different amino acids (or chemical bonds) feel very different field strengths, which makes the prediction of SERS spectra complicated. To address this intricate trinity, researchers have explored three main aspects: the electromagnetic field, protein conformations on the surface, and polarizability derivatives. By considering above aspects, a hybrid quantum-classical strategy represents the state-of-the-art method for simulating protein molecular species.
Figure 28
Figure 28. Prediction and modeling of protein molecular species. (a) Three different fields involved in SERS: Raman spectroscopy, nanosurface science, and nanoplasmonics. The most representative examples for modeling nanoplasmonics (left) and nanosurface science (right) in the very beginning are illustrated. (601,610). (b) Models for protein in different environment: powder, solution, adsorbed protein, and free protein in the hotspots. Adapted from ref (602). (c) MD simulation can be used for screening orientations of peptides or proteins. (d) Quantum and classical electrodynamics indicate the distance-dependent phenomenon for SERS. (e) SERS trajectory in Euler space can be described as different orientations in the hotspots. (f) Schematic diagram of SPARC for calculating SERS spectra of proteins. Adapted from ref (626).
The first essential step in understanding SERS spectra of proteins is to simulate the localized EM field. To date, various simulation methods such as Finite-Difference Time-Domain (FDTD), have been used to obtain optical responses without considering the presence of the protein. By calculating EM enhancement factor of Ag spheres with different configurations, (600) Xu et al. has demonstrated single molecule SERS signal of Hemoglobin only comes from the “hotspots” between Ag NPs (Figure 28a left). (601) Furthermore, Wang et al. proposed a model featuring a quasi-uniform electromagnetic field generated in the hotspots (Figure 28b), accounting for the similarity of spectra between SERS and normal Raman. (602) It should be emphasized that surface selection rules are crucial for interpreting SERS spectra of proteins, as only the amino acids close to the metal surface with a polarizability component parallel to the direction of the EM can be selectively enhanced. Therefore, accurate description requires not only distribution and direction of EM field but also orientation of proteins and corresponding polarizability derivatives of each bond. To determine these parameters, DFT with a cluster-molecule model is the most powerful method (Figure 28a right), providing theoretical spectra that align well with the experimental spectra of amino acids and peptides. (603−610) Moreover, Huang et al. demonstrated the feasibility for predicting the normal Raman spectrum of the SARS-CoV-2 S1 subunit by calculating its fragments with hundreds atoms individually. (611) However, these methods still require enormous resources and is almost impossible to calculate Raman spectra of proteins with quantum mechanics. In this regard, molecular dynamics is indispensable (Figure 28c). which not only provides important information on orientation of proteins, but also offers a valuable insight for understanding dynamic SERS spectra. (612) Since Alvaro et al. first applied molecular dynamics to understand peptide orientation on a Ag surface, numerous studies have employed molecular dynamics to interpret SERS spectra. (288,327,613−620) For instance, Ma et al. observed consistent distance-dependent SERS features based on the intensity of aromatic amino acids and conformation from molecular dynamics. (621) Nowadays, it is even possible to obtain SERS spectra of protein species using Ab Initio Molecular Dynamics (AIMD) calculations. (622)
To faithfully address the intricate trinity, i.e. the electromagnetic field, protein conformations and polarizability, involved in SERS process, pioneering studies have established a hybrid quantum-classical strategy for analyzing the SERS spectra of small molecules, which has since inspired protein simulations. As depicted in Figure 28d, Mullin et al. combined quantum and classical electrodynamics to calculate the SERS spectra of pyridine at varying distances from a Ag substrate, revealing the distance-dependent field intensity. (623,624) Banik et al. successfully deciphered time-dependent changes in SERS spectra, uncovering the motions of small molecules within hotspots (Figure 28e). (625) Taking advantages of the tensor nature of Raman spectroscopy, they calculated the SERS spectra of molecules in different orientations by rotating the partial derivatives (PDs) of each vibration, yielding results that closely matched experimental data. As indicated in Figure 28f, it is important to emphasize that the decay nature of the strongly confined electric field generated by LSPR enables high spatial resolution of SERS in z-axis, functioning like molecular-scale computed tomography. Based on this sectioning capability and the tensor nature, Ma et al. proposed a separable PDs-based algorithm with rotational coarse-grained model (SPARC) to isolate and obtain the PDs of each amino acid. This algorithm allows simulation of SERS spectra of a complex protein in seconds through summing SERS spectra of amino acids in different sectioning layers. (626) By comparing the experimental SERS spectrum with simulated spectra of proteins in various conformations, SPARC can reconstruct the 3D protein structure with near-atomic precision. However, handling all the amino acids separately and low efficiency for screening conformations come to the shortcomings of SPARC, which can be solved with precise, data-driven approaches. Recently, a work done by Hu et al. applied random forest model to obtain the simulated SERS spectra for specific molecule, which markedly improved computational efficiency and accuracy. (627) Moreover, the graph neural networks (GNN)-based DetaNet utilizes the gradient of neural networks to calculate partial derivatives of various properties, enabling the prediction of the Hessian matrix and polarizability with the same accuracy as conventional theoretical methods, thus offering the potential for faster SERS spectrum simulations of proteins. (599)
8.4. SERS Detection of Liquid Biopsy-Based Protein Biomarkers
Protein biomarkers in body fluids are increasingly being used as liquid biopsy biomarkers for noninvasive disease detection and cancer screening. However, these disease-associated protein biomarkers are typically present in low abundance and coexist with other high-abundance biomolecules, making their detection extremely challenging. Common methods for serum protein detection in clinical laboratories, such as enzyme-linked immunosorbent assay (ELISA) and electrochemiluminescence immunoassay (ECLIA), offer detection sensitivities at the picomolar level, depending on the antibody–antigen interaction. (628) However, these methods are limited to single-plex detection, require specialized equipment, and are prone to nonspecific binding interferences. The development of various SERS immunoassays and hand-held Raman spectrometers presents a promising solution to these challenges in detecting protein biomarkers in liquid biopsy samples.
Direct SERS-based detection of target proteins typically relies on target-specific ligands and the resulting changes in Raman fingerprints upon protein capture. Gallo et al. developed a fast, easy, and sensitive SERS-based system for detecting the LGALS3PB (90K) biomarker using antibody-functionalized, Au-coated glass surfaces. (629) Raman spectra were collected and analyzed through principal component analysis, revealing distinct changes after interaction with target proteins. This method demonstrated sensitivity to detect 1 pg/mL of 90K proteins in serum samples within 30 min. Muhammad et al. fabricated a highly ordered Au NP array as the SERS substrate and functionalized its surface with aptamers specific to IL-6 (Figure 29a). (630) The aptamer exhibited conformational changes upon interacting with IL-6, corresponding to changes in the Raman intensity ratio. This method was sensitive enough to detect 0.8 pM of IL-6 in simulated serum samples. The authors further validated the effectiveness of the aptamer-SERS biosensor in monitoring IL-6 levels in the serum of X-ray-treated mice. However, both methods face challenges in multiplex protein detection.
Figure 29
Figure 29. SERS immunoassays for liquid biopsy-based protein marker detection. (a) The Au NP array functionalized with IL-6 aptamers for detecting IL-6 through changes in the aptamer’s SERS signal. Adapted from ref (630). (b) A digital single-molecule nanopillar SERS platform for parallel counting of four types of cytokines. Adapted from ref (631). (c) A plasmonic internal standard-embedded LFA-SERS platform for the duplex detection of protein markers. Adapted from ref (636). (d) A multiplex, pump-free SERS microfluidic chip for the duplex detection of protein biomarkers across multiple samples. Adapted from ref (638).
Probe-based SERS immunoassays present significant advantages for robust multiplex detection of protein biomarkers in liquid biopsies. For instance, Li et al. developed a nanopillar SERS platform for monitoring four cytokine biomarkers in melanoma patients undergoing immune inhibitor blockade treatment (Figure 29b). (631) Single cytokine detection was achieved by superdiluting samples to align with the Poisson distribution and labeling cytokines with single-particle active SERS nanotags. Confocal SERS spectral mapping was used for signal collection, and Raman signal pixels were manually counted, achieving attomolar sensitivity. This method was applied to clinical samples and successfully identified elevated cytokine levels in melanoma patients at higher risk of severe immune toxicities. However, the high cost of fabricating Au-topped nanopillars and the labor-intensive sample detection and data analysis processes may limit its clinical applications.
To address these limitations, Lee et al. proposed a more cost-effective and rapid SERS platform for multiplex detection of cardiac biomarkers, aimed at the rapid screening and monitoring of acute myocardial infarction (AMI). (632) The platform involved functionalizing Au substrates with capture antibodies that had been cleaved using tris(2-carboxyethyl)phosphine hydrochloride. Au nanocubes were used as SERS nanotags for protein labeling, and a portable Raman spectrometer was employed for signal acquisition, achieving sensitivity as low as 6.56 fg/mL for creatine kinase muscle brain and 11.81 fg/mL for cardiac troponin I. This platform allowed for rapid (10 min) screening of acute myocardial infarction severity in emergencies and monitoring of both markers post- acute myocardial infarction onset. Similarly, Ouyang et al. utilized an antibody-based SERS immunosensor for duplex detection of serum cytokines to assess tumor microwave ablation outcomes. (633) The sensor demonstrated detection sensitivities of 82 fg/mL for CC chemokine ligand 20 (CCL20) and 0.096 fg/mL for epidermal growth factor (EGF). The consistent results between the SERS immunosensor and ELISA in measuring CCL20 and EGF levels underscore the potential clinical utility of SERS for protein biomarker detection.
Researchers from the same group reported using LFA-SERS for the simultaneous quantification of two serum protein biomarkers, CCL20 and EGF. (634) In this assay, two test lines on nitrocellulose membranes were functionalized with capture antibodies specific to CCL20 and EGF. When human serum samples were loaded onto the sample pad, capillary action drove the sample through the conjugate pad, allowing it to interact with SERS nanotags, and then continued toward the test strip surface. The presence of CCL20 and EGF resulted in the formation of a sandwiched immunocomplex composed of capture antibodies, target proteins, and SERS nanotags, which generated SERS signals upon laser excitation. This LFA-SERS immunosensor achieved detection sensitivities as low as 64 pg/mL for CCL20 and 90 pg/mL for EGF. The performance of LFA-SERS was further validated in serum samples from five healthy donors and 12 hepatocellular carcinoma patients, both before and after tumor microwave ablation treatment. The study found that the tumor microwave ablation complete treatment significantly elevated CCL20 levels and decreased EGF levels in the serum of hepatocellular carcinoma patients; while incomplete treatment caused a slight decrease in CCL20 levels and a significant increase in EGF levels.
To enhance the detection sensitivity of LFA-SERS, Gao et al. redesigned the LFA strip by combining nitrocellulose membranes with a Au nanopyramid array-coated quartz substrate, both mounted on a common adhesive backing layer. (635) The Au nanopyramid array was designed to create “hot spots” and was further functionalized with capture antibodies, serving as the test zone. To facilitate smooth migration across the boundary between the nitrocellulose membrane and the quartz substrate, a surfactant bridge composed of Tween 20 and sucrose was applied to the quartz substrate. Diluted clinical blood plasma and SERS nanotags flowed through the conjugate pad and formed a complex of capture antibodies, target antigens, and SERS nanotags in the test zone. The entire process, from sample loading to data acquisition, took 30 min and was sensitive enough to detect 5.0 pg/mL of S-100β, a traumatic brain injury (TBI) protein biomarker, in blood plasma. The SERS results for quantifying S-100β in blood samples from six clinical traumatic brain injury patients were comparable to ELISA data.
To address signal variations caused by the random distribution of SERS nanotags on nitrocellulose membranes, Fan et al. introduced a plasmonic internal standard-incorporated LFA-SERS method (Figure 29c). (636) Unlike the approach by Su et al., (634) this method achieved multiplex detection of two target proteins on a single test line while also providing internal calibration by measuring in situ signals of Raman reporter molecule-embedded Ag–Au alloy NPs within nitrocellulose membranes. Compared to conventional LFA-SERS, this method significantly improved uniformity (25.22% vs 13.68%) and enhanced the detection sensitivity of carcinoembryonic antigen (CEA) (126 pg/mL vs 39 pg/mL). The SERS results also showed strong correlation with ECLIA measurements of carcinoembryonic antigen and neuron-specific enolase (NSE) in serum samples from 10 early stage lung cancer patients. Furthermore, SERS results effectively discriminated between early stage lung cancer patients and healthy donors.
Interestingly, using plasmonic nanomaterial-coated filter papers as SERS substrates also demonstrated excellent sensitivity in multiplex protein marker detection. Lu et al. developed a paper-based SERS platform using Au nanoflower-coated hydrophobic filter paper as the substrate and Au–Ag nanoshuttles as SERS nanotags. (637) This platform enabled the simultaneous detection of squamous cell carcinoma antigen (SCAA) and osteopontin (OPN) in cervical cancer serum, achieving detection limits as low as 8.628 pg/mL for squamous cell carcinoma antigen and 4.388 pg/mL for osteopontin in human serum samples. The feasibility of this SERS-based immunoassay platform was further validated by testing 150 serum samples, including those from healthy subjects, patients with varying stages of cervical intraepithelial neoplasia (CINI-III), and cervical cancer patients. The results indicated that both protein biomarker levels increased with disease progression.
Lab-on-a-chip technology, which enables automated analysis of complex biochemical reactions in microscale environments, presents an attractive approach for disease screening when combined with SERS immunoassays. Cao et al. proposed a multiplex, pump-free SERS microfluidic chip utilizing a one-step recognition release mechanism (Figure 29d). (638) The chip featured a novel Au nanocrown array as the sensing unit in the platform’s detection zone, enabling rapid and specific detection of protein markers in multiple samples simultaneously. The aptamer-functionalized Au nanocrown array captured specific protein markers, causing the complementary strand of the aptamer carrying the Raman signal molecule to detach, reducing the SERS signal. This platform achieved a 15 min measurement of serum protein biomarkers (hnRNP A1 and S100P) for early colorectal cancer diagnosis, with detection limits of 31 ng/mL for hnRNP A1 and 57 ng/mL for S100P. The SERS microfluidic chip was further validated in serum samples from 30 healthy donors and 30 colorectal cancer patients, showing good agreement with ELISA results, suggesting great potential for clinical applications.
8.5. Metabolite SERS Analysis
Metabolites are among the most important biomarkers in health management, being constantly expressed during natural metabolic pathways and altered in concentration and type during infection, ill-health, and disease. Their intermediate nature and importance in disease control mean that detection methods involving in situ observation by rapid, on-the-spot techniques are highly desired. While typical metabolomics techniques involve lengthy sample preparation and analysis, SERS has become a highly sensitive method for the detection of multiple Raman-active metabolites simultaneously, even within environments containing other biomolecules. Recent focus has been placed on studying cancer and tumor-associated metabolites, secreted upon reprogramming of the native tissue to tumor microenvironment. (639) Different types of plasmonic substrates, e.g. produced by simple methods such as drop-casting or more complex Au NP superlattices, have been used to conduct SERS measurements for metabolite sensing. Examples include the evaluation of purine-based metabolites such as kynurenine or amino acids containing an aromatic ring, such as tryptophan and phenylalanine. These metabolites are highly relevant because amino acids form the building blocks of the extracellular matrix (ECM), (640) and changes in ECM composition via tumor microenvironment remodeling have been associated with various biological processes such as ECM proteolysis and metastatic-associated epithelial-mesenchymal transition (EMT). (641) One such example is the augmented immunomodulatory activity of the indoleamine 2,3-dioxygenase 1 (IDO-1) enzyme, responsible for tryptophan to kynurenine catalysis, detected in the plasma of lung, gynecological, breast, colorectal, and melanoma malignancies. (642) The ratio between tryptophan and kynurenine content can be monitored using the SERS peaks at 760 and 560 cm–1, respectively (Figure 30a). (643) Subtle changes in peak intensity could also be detected in metabolite-spiked cell media, albeit with a reduced limit of detection compared to measurements undertaken in water. It should be considered that the presence of multiple metabolites, and/or biomolecules such as proteins, drastically affects the sensitivity and selectivity of SERS measurements. For example, protein fowling and unwanted metabolite binding to plasmonic substrates hinder their use in microfluidic systems for time-resolved measurements. (644) This issue (known as the SERS memory effect) can be resolved by using substrates where the plasmonic NPs would be covered by a layer of a thermosensitive polymer. (113) Upon irradiation with the same SERS irradiation laser (at a sufficiently high laser power density, e.g., 0.064 mW/μm2), local heating occurs, leading to localized removal of PLGA and exposure of the underlying plasmonic substrate for SERS measurements. Repeated application of this operation can be applied for real-time monitoring of metabolites, with a high degree of spatial and temporal control. By using this and other modifications to the sensing setup, high throughput SERS measurements can be performed to train machine learning algorithms, which can subsequently be used to identify the presence of selected metabolites. This idea has been recently applied to the evaluation of cell death mechanisms. (645)
Figure 30
Figure 30. SERS analysis of metabolites. (a) SERS analysis of the conversion of tryptophan (Trp) into Kynurenine (Kyn), catalyzed by the IDO-1 enzyme. Reproduced from ref (643). Copyright 2020, John Wiley and Sons. (b) Evaluation of cell death mechanisms by application of SERS and machine learning. Reproduced from ref (646). Copyright 2024, The Authors.
Similar substrates have been also applied in more complex biological models. Again based on the activity of the IDO-1 enzyme, alterations in tryptophan to kynurenine conversion were detected in cell media derived from in vitro spheroids mimicking the heterogeneity of pancreas tumors. (646) In this case, spheroids composed of cancerous epithelial PANC-1 cells and cancer-associated pancreas fibroblasts were formed, and cell media were removed for SERS analysis at specific time points. As expected, the cellular interplay in the more representative tumor microenvironment resulted in significantly increased expression of IDO-1, resulting in an upregulation of kynurenine, which was detected by SERS and confirmed via traditional ELISA. Again, the application of machine learning allowed the discrimination between conditions related to promotion or inhibition of the IDO-1 metabolic pathway (Figure 30b). A different metabolic pathway associated with tumor microenvironment alterations is the methionine salvage pathway, in which mutations in the methylthioadenosine phosphorylase (MTAP) enzyme are known to lead to an accumulation of its main substrate, 5′-methylthioadenosine (MTA). Although the role of MTAP in cancer is still not fully understood, it is well-known that many cancers express a deletion of MTAP, in turn leading to alterations in MTA levels. By using Au NP-based SERS substrates, accumulation of MTA was identified in supernatants from cells exhibiting deletion of the MTAP enzyme. (13) Again, cell coculture models, designed to better represent the tumor microenvironment in vitro, effectively showed an intercellular crosstalk involved in metabolic activity, as shown by the ability of fibroblasts to metabolize extracellular MTA. This is an interesting example of the application of high-throughput SERS analysis to discover unknown cellular communication mechanisms that play a significant role in the development of cancer or other diseases.
8.6. Metabolic Phenotyping (SERSome)
Molecular profiling plays a critical role in providing a comprehensive view of complexed biosystems, generally performed in aim of systematic monitoring, biomarker screening and disease diagnosis. Label-free approaches accompanied by related computational methods are used for this purpose. While the challenge is the limited and unrobust information one can acquire from one single spectrum since the molecular composition may emerge stochastically in a certain probe volume and on the electromagnetic hotspots (which also causes signal fluctuations due to differences in electromagnetic fields and molecular orientation). Mean spectrum is among the simplest and most applied way to reduce the fluctuations, while rare events generated by molecules of trace concentration, poorer affinity to metallic surface and/or lower cross sections could be averaged out, leading to information loss (Figure 31a).
Figure 31
Figure 31. SERSome for robust metabolic profiling. (a) The concept of SERSome and the comparison with single spectra and averaged spectra for the detection of complex molecular systems. Reproduced from ref (652). (b) Convolutional neural network for SERSome analysis and SERS-based disease diagnosis. Reproduced from ref (648). (c) SERSome-based biomarker screening and the subsequent biological validation of the biomarker candidates. Reproduced from ref (650).
To this point of view, the concept of SERSome was recently proposed, (647,648) using a whole spectral set rather than a single spectrum or the mean from a handful of spectra to preserve all the molecular information that could be potentially captured (Figure 31a). This approach is intended to facilitate more comprehensive profiling with enhanced capability of identifying biomarkers and classifying different biological states. SERSome has primarily exerted its effectiveness in metabolic profiling as it is sensitive enough for rapid small molecule detection in liquid samples compared to spontaneous Raman scattering-based techniques. Recently, progress has been witnessed in disease diagnosis using human serum (648) and cellular profiling even in the single-cell level using lysates and culture medium. (649−651)
Pretreatment protocols have been optimized for efficient SERSome-based metabolic profiling of different kinds of bioliquids. Specifically, a substantial content of proteins and other large molecules should be avoided, otherwise the detection sensitivity would be reduced due to less available electromagnetic hotspots, for example, by protein corona effect. (648,649) Such a pretreatment step can also primarily ensure the research object to be metabolite species. While it should also be noted that, as for SERS detection, chemicals involved in the pretreatment procedures should be taken keen consideration for minimal interfering signals and influence to SERS substrates. (650)
The method for spectral set analysis should be carefully selected as the molecular signatures are embodied in a 2-dimensional data matrix. Generally, Pearson’s correlation can be used at the system setup stage to roughly estimate the spectrum number for reproducible profiling under the criteria of adequate consistency between the mean spectra from two spectral subsets acquired from one sample. (648) While in regard to the stochastically detected molecular signatures within a spectral set, Wasserstein distance is used to directly compare the similarity between two spectral set by computing the variation between the data distributions. This index can also be utilized to differentiate sample classes. (652) Deep learning methods including convolutional neural network lie in another major route for SERSome analysis given the advantage in spectrogram texture extraction. Multiple analysis tasks including background removal, data augmentation and classification can be incorporated into the system for improved classification accuracy (648) (Figure 31b). As SERSome has revealed richer molecular information with higher robustness, classical statistics and interpretable models have been explored to indicate biomarkers. Typically, Gradient-weighted Class Activation Mapping (Grad-CAM) can be used as an additional deep learning module following the classification module by retrospectively excavating the most important features contributing to the classification. By referring to the spectral bands indicated in the saliency map, biomarkers can be deduced according to their characteristic vibrational signatures. (648) As for any techniques for biomarker screening, subsequent biological experiments are critical for biomarker validation (Figure 31c). (650,653)
8.7. Selective Small-Molecule Metabolite SERS Sensing
SERS substrate offers great flexibility to be tuned by surface engineering for selective small-molecule metabolite capturing and sensing. We identify two main strategies in achieving selective metabolite sensing: 1) analyte manipulation and capturing, and 2) hybrid techniques (Figure 32). The first strategy can be further categorized into chemical analyte capturing and physical confinement, both of which focus on selective enrichment of the target analyte near the hotspot to amplify their SERS signals. Specifically, chemical analyte capturing utilizes chemical interactions between engineered NPs and the target analytes to facilitate electron transfer and facilitate analytes’ access to the NPs’ electromagnetic field, whereas physical confinement selectively concentrates metabolites near the nanosensor surface to enhance intermolecular interactions. On the other hand, hybrid techniques couple SERS with another analytical technique to synergistically enable enhanced performance by accumulating analyte-specific signals to distinguish the target analytes SERS signals from other interferences. It is of note that multiple strategies are usually integrated in the development process of a SERS-based sensor to achieve both desired sensitivity and specificity.
Figure 32
Figure 32. Overview of strategies for selective small metabolites sensing.
8.7.1. Analyte Manipulation and Capturing
To manipulate and enrich the target metabolites at the SERS hotspot, two main approaches are chemical analyte capturing and physical analyte confinement. For selective metabolite sensing, three strategies of chemical analyte capturing are (i) inducing chemical interaction using small probe molecules, (ii) specific capturing using biomolecular probes, and (iii) array-based sensing.
| i. | Inducing chemical interaction using small probe molecules. In the chemical analyte capturing strategy, typically a self-assembled monolayer (SAM) of small probe molecules is grafted onto the SERS substrate to selectively form chemical interaction with a specific functional group on the target metabolites. SAMs are thin layers of molecules spontaneously organized into ordered structures on a substrate, with a headgroup binds to the substrate and a tail group that orient to surrounding environments, capable of inducing interactions. (654−657) By tuning the chemistry of the tail group, selective metabolite sensing can be achieved by either selective capture the target metabolite or inducing analyte-specific signal. (658,659) Small probe molecules are able to induce a wide range of interaction depending on the functional group present on the probe, from covalent such as boronic ester and imine chemistry, to noncovalent such as electrostatic, hydrogen bonds, dipole–dipole, pi-pi stacking, and van der Waals interaction. (382,436,660,661) For example, 4-mercaptoboronic acid (4-MPBA) was employed to selectively form boronic ester with analytes containing vic-diol group such as pregnane and tetrahydrocortisone in urine, enabling quantification down to 10–10 M for accurate diagnosis of miscarriage in pregnant women. Notably, the small probe molecule strategy does not require selective interaction with a specific analyte, but it can form interactions with a wide range of analytes, as long as each of them yield analyte-specific spectral changes. In principle, the interaction with analytes should result in probe-analyte interactions with either specific geometry configuration or specific interaction energy to yield analyte-specific SERS peak shift or change in intensity. Particularly, 4-mercaptopyridine (MPY) was employed to differentiate among four chondroitin sulfates, which are isomeric analogs consisting of similar core structures but differed in substitution group position and number (Figure 33a). (662) The molecular recognition capability is achieved by 1) charge complementarity and 2) geometric complementary/mismatch between the chondroitin sulfate’s sulfation patterns and the rigid binding pocket formed by MPY’s pyridine N atom and adjacent aromatic H atom. As a result, a classification accuracy of >97% and multiplex quantification error at <3% is achieved for all 4 chondroitin sulfates at micromolar concentration. In another study, 6-thioguanine was employed to differentiate among 16 glycerol derivatives consisting of at least two H-bond forming functional groups at >95% accuracy. Such high accuracy stemming from different energies of H-bond network in the 6-thioguanine-analyte complexes and the specific interatomic distance between 6-thioguanine’s binding site and the analytes, resulting in an analyte-specific spectral changes. Collectively, these studies illustrate a wide range of use of small molecular probes for selective metabolite sensing, demonstrating a great potential for biomedical applications due to their simplicity of fabrication and high tunability to adapt to various types of metabolites. | ||||
| ii. | Specific capturing using biomolecular probes. In the scenario where exceptional metabolites selectivity is required, the use of biomolecule probes such as antibodies and aptamers is preferred to form a lock-and-key complex with a perfect receptor-analyte geometry matching, despite being more expensive to produce and require stricter storage conditions. (663−665) It is of note that this strategy does not rely on the intrinsic signal of the analytes, thus requiring an additional SERS nanotag for signal transduction. Antibody offers exceptional selectivity by forming multiple interactions with the target analyte with high geometric complementarity. For instance, a SERS sandwich immunosensor comprising an antibody attached to SERS substrate Au nanopillars was employed to capture and detect three types of mycotoxin: ochratoxin A, fumonisin B, and aflatoxin B1 at sensitivity down to picogram/mL in human serum (Figure 33b). (666) An alternative option for exceptionally selective analyte capturing is aptamer, which has lower production cost and higher stability, thus more suitable for clinical applications. For instance, the simultaneous detection of two mycotoxin Ochratoxin A and Aflatoxin B1 in maize meal at pg/mL level were achieved by using an aptamer-functionalized Ag@Au core–shell NPs. (667) Collectively, biomolecular probe demonstrates a great potential for SERS-based metabolite sensing due to their high selectivity and customizability to adapt to various types of analytes, ranging from small metabolites to macromolecules. | ||||
| iii. | Array-based strategies. So far, our discussion on chemical analyte capturing is focusing on the specific identification and quantification of a single analyte and/or a class of analyte. However, practical biomedical applications often require multiplexing capabilities to concurrently identify and quantify multiple metabolites or to differentiate complex, multicomponent mixtures without explicitly analyze an individual metabolite. In such scenario, array-based SERS sensors are an excellent candidate because it can accumulate chemical insight from multiple substrates with different chemistry to produce high-dimensional signal patterns unique to the analyte mixture which reflects a specific disease state. The potential of array-based methods in biomedical applications is evidenced by a substantial increase in the number of studies employing them for analysis in breath, urine, saliva, etc. (435,668−671) For example, by accumulating breathomic profile encoded as spectral changes in three small-molecule probes, COVID-19 detection at sensitivity of 96.2% and specificity of 99.9% were achieved (Figure 33c). (435) This is because different small molecule probe consists of different functional group such as pyridine, carboxylate, and amine, to interact with various analytes in breath (alcohols, aldehydes, ketones, aromatic compounds) via a wide range of interactions such as H-bond, π–π interaction, dipole–dipole interaction, thus providing a more comprehensive breath profile. Collectively, the examples discussed in this section demonstrate a huge potential of chemical analyte capturing for selective metabolite identification and quantification for disease diagnosis and monitoring. | ||||
Figure 33
Figure 33. Analyte manipulation and capturing strategy for selective small metabolite sensing. (a) Schematic illustration of the use of charge and geometry complementarity/mismatch to direct the probe–analogue coupling toward the chondroitin sulfates’ isomerism sites and induce multidentate interactions for formation of analogue-specific complex geometries when 4-mercaptopyridine (MPY) is selected as the multidentate probe, yielding differentiable SERS spectra as evidenced by distinct clusters on PCA score plot. (b) Detection of mycotoxins using SERS competitive immunoassays. (c) SERS-based sensor chip consisting of multiple SERS nanotags for accurate COVID-19 detection. (d) Mechanism of selective physical confinement using MOF, in which molecules with diameter larger than the pore aperture (2-naphthaldehyde) is separated , whereas 4-ethylbenzaldehyde can diffuse into the MOF, thus provide accurate quantification of 4-ethylbenzaldehyde. Reprinted and adapted with permission from (a) ref (662), (b) ref (666), (c) ref (435), and (d) ref (675). Copyright 2018, 2023 Wiley. Copyright 2022, American Chemical Society.
8.7.2. Selective Physical Confinement
Physical confinement aims to selectively concentrate metabolites based on their physical properties and bring the analytes proximal to the nanosensor surface for enhanced SERS effect, thus specifically boosting SERS intensity and detection sensitivity of the target analyte. A commonly employed strategy for physical confinement is the use of metal organic framework (MOF) to selectively confine the metabolites of interest based on their molecular size. (672−674) MOFs are a class of highly porous crystalline material comprised of metal nodes and organic linkers, capable of selective trapping molecules with molecular size smaller than their pore aperture, referred to as molecular sieving effect. (674) For example, ZIF-8-coated Au superparticles demonstrate selective adsorption of 4-ethylbenzaldehyde, which is a lung cancer biomarker in breath, but not 2-naphthaldehyde (Figure 33d). (675) Another example of selective analyte enrichment is the use of AuNP/MIL-101 for selective adsorption of small molecule such as 4,4′-bipyridine in the presence of bigger molecule such as poly(4-vinylpyridine) as interference. (676) Leveraging the molecular sieving capabilities, the author showcases detection of p-phenylenediamine down to 0.1 ng/mL in the sewage water and river water. Such molecular sieving effect showcase MOF’s potential for practical applications, in which exclusion of macromolecules and cellular species is crucial for accurate detection of small metabolites.
8.7.3. Hybrid Techniques
Hybrid techniques, which couple SERS with another analytical method, enhance the metabolites detection selectivity by 1) combines multiple types of transducing signal to complement the information provided by each other (multimodal), or 2) couples analyte detection methods with additional molecule adsorption enhancement techniques (hyphenated). In a multimodal technique, an additional analytical method is employed, serving as a cross-validation to increase the reliability of SERS analysis, or two complement the limitations of SERS. For example, a combination between SERS and photoacoustic takes the advantage of each other for accurate location of diseased tissue and quantitative analysis of H2O2 for progress tracking of the anti-inflammatory treatment in real-time (Figure 34a). (677) Specifically, while SERS provides excellent sensitivity and specificity for H2O2 detection, its use for real-time and in vivo quantification detection has been limited due to poor tissue penetration. In this aspect, photoacoustic has enhanced tissue penetration depth and accelerated images acquisition to guide SERS in finding the lesion site, highlighting the mutual supplementation of the two modes. Although multimodal techniques offer enhanced analytical performance, it is important to note that a two-in-one instrumental platform must be built, and the SERS platform needs to be compatible with the coupling techniques.
Figure 34
Figure 34. Multimodal techniques for selective small metabolites sensing. (a) Multimodal technique using SERS and photoacoustic for accurate in vivo quantification of H2O2. (b) Hyphenated technique using electrochemical-SERS (EC-SERS) to manipulate the analyte (d- and l-tryptophan) orientation and adsorption onto the Au nanoporous bowl (NPGB), showing superiority of EC-SERS, as evidenced by distinct clusters on the PCA score plot, in contrast to the conventional SERS (no Vapplied) which results in overlapping clusters. Reprinted and adapted with permission from (a) ref (677) and (b) ref (434). Copyright 2021, Wiley. Copyright 2021, American Chemical Society.
Besides multimodal techniques, the hyphenated technique offers enhanced selective small metabolites detection by coupling SERS with a technique capable of performing analyte separation and/or manipulation, such as electrochemical and chromatographic technique. This has an immense potential in biomedical applications because the target analytes often coexist with other interfering biomarkers and macrobiomolecules present in the biological matrices. For example, electrochemical-SERS (EC-SERS) enables differentiation between stereoisomers by altering adsorption orientation of each analyte under applied voltage. (434) This was demonstrated in qualitative and quantitative analysis a mixture of enantiomers (l-/d-tryptophan and R/S-propranolol), using nanoporous Au bowl as the SERS substrate (Figure 34b). Such stereoisomers identification and quantification are extremely important in diverse field ranging from pharmaceuticals to disease diagnosis. Another example of hyphenated techniques is chromatography-SERS for selective metabolites detection by separating it from its complicated matrices, which is demonstrated in the development of a paper chromatography-SERS individual identification of lycopene and β-carotene in a mixture. While many new hyphenated techniques show promising potential, most are still in the early stages of development, with relatively few studies conducted on real sample. This is the same case for multimodal technique, which suggests that more studies should be done to further improve analytical performance and reduce analysis time and cost to accelerate the translation of such hybrid SERS techniques into practical biomedical applications.
Collectively, we demonstrate the potential of SERS for selective small metabolite sensing by using two main strategies: analyte manipulation and capturing, and hybrid techniques. Such selective and accurate analyte identification and quantification at ultratrace levels in the presence of interferences potentially has immense impact on biomedical applications due to the small metabolites’ significant roles in many biological processes, indicating disease state and progress. However, to further drive the translation of SERS-based technologies for small metabolites sensing into practical usage, we envisage three main aspects that need to be tackled. First, it is required to benchmark SERS against gold standard methods such as chromatography and immunoassays to ensure the robustness and reliability of SERS platform. This is critical when moving from lab-based and in vitro sample to practical samples due to the presence of interferences and the samples’ heterogeneity, meaning that the target metabolites does not distribute evenly within the sample. Second, although there are various methods for enhancing selective small metabolites sensing at high sensitivity and selectivity, it is important to note that there remain factors that need to be considered for the practicality of the method, such as reproducibility, portability, time and cost for manufacturing, storage, sample preparation and measurement. For instance, upscaling can significantly alter the fabrication process because the synthesis of metal NPs for SERS-based sensor is strongly influenced by mass and heat transfer, thus requiring additional cost to maintain the sensors’ quality. In some cases, SERS sensors that require cheaper and less sample processing have higher fabrication cost and vice versa, thus balancing between these factors need to be considered. Finally, collaboration between scientists, industry, and clinicians is crucial to establish standardized protocols for sensor fabrication and storage, sample preparation and measurement, and data analysis. We envisage that through such concerted efforts, we can fully realize the potential of SERS-based technologies for small metabolites sensing and deploy them in practical settings for biomedical applications.
8.8. Single-Cell Metabolite SERS Monitoring
Single-cell metabolomics directly indicates the phenotypic diversity of single cells and offers immediate insight into how cells respond to their environments. Cells and the extracellular environment interact dynamically through a variety of molecules, including metabolites. (678) However, measuring metabolites secreted from a single cell is challenging due to their rapid metabolic dynamics and wide molecular diversity. Additionally, small-molecule metabolites cannot be readily amplified. Thus, monitoring these rare and low-concentration metabolites requires highly specific and accurate analytical techniques.
Single-cell metabolomics involves manipulating minute volumes of materials, which creates a high demand for sample handling and transfer techniques. Droplet microfluidics is a feasible high-throughput single-cell technology. (679) It encapsulates individual cells into water droplets of a picolitre volume using immiscible oil–water two phases, providing independent and closed chambers for long-term cell culture. Rapidly accumulated cell secretions in such a small volume can arrive at a detectable level. In addition, the consumption of probed reagents is significantly reduced. The combination of SERS and droplet microfluidics provides a robust platform for studying single cells and addresses several critical issues of SERS detection. For instance, the integrated platform can precisely control the aggregation extent of plasmonic NPs and the mixing efficiency of metal colloids and analytes accurately via the flow rate regulation, which can maintain coincident probability for hotspots and improve reproducibility in quantitative analysis. In addition, the droplet microfluidic system can accomplish high-throughput, consistent droplet preparation, which not only provides homogeneous conditions for robust and reliable analysis, but also allows for high-dimensional computational tools (e.g., machine learning) to handle the rich and big data sets, enabling exploratory analysis of complicated biosamples, such as exploiting biological component interaction networks or patterns to reveal latent cellular subpopulations. Therefore, the combination of SERS and droplet microfluidic technology is expected to be a promising and efficient bioanalytical tool, especially for single-cell metabolomics studies.
Aiming at tracing the single-cell metabolites, Xu et al. developed a series of microdroplet-based SERS analytical platforms to achieve the in-drop SERS assays, and the sensitivity of which can satisfy the single-cell detection level. In 2019, they introduced the SERRS effect into the droplet microfluidics to achieve ultrasensitive analysis of a minimal amount of alkaline phosphatase (ALP) in a single cell. (680) The cell suspension, ALP-catalyzed substrate BCIP (5-bromo-4-chloro-3-indole phosphate), and SERS-active AuNPs were spiked into the water phase to produce water-in-oil droplets. The colorless BCIP experienced a hydrolysis reaction catalyzed by ALP, and the oxidized intermediate compound formed blue BCI (5, 5′-dibromo-4,4′-dichloro-1H,1H-[2, 2′]biindolylidene-3,3′-dione), which is a resonant Raman-active species. Thus, the single-cell ALP activity was evaluated by monitoring the SERRS intensity of BCI enhanced by AuNPs, and the lowest detectable ALP concentration was as low as 1.0 × 10–15 M.
To detect the small amount of cytokines secreted by a single cell, a droplet technique was integrated with the magnetic field amplification SERS strategy for the simultaneous detection of two cytokines secreted by the single cell. (681) Immuno-magnetic beads (iMBs) and immuno-Ag NPs were packaged with single cells in water-in-oil droplets. Cytokines produced by the cells would bridge these immuno-probes to form nanoaggregates, switching on the SERS signals of reporters presettled above the iMBs. This method achieved the highly sensitive (up to 1.0 fg/mL), repeatable, and selective detections of vascular endothelial growth factor (VEGF) and IL-8 at the single-cell level. Later, Xu and co-workers modified this in-drop immunoassay with an elaborate bioconjugation strategy above the cell membrane of the probed cell surface. (682) By grafting the membrane proteins with Sulfo-NHS-LC-biotin (sulfosuccinimidyl-6-[biotin-amido]hexanoate), the capture probes and SERS nanotags were anchored to the cell membranes with secreted proteins as bridges, resulting in cytokine enrichment above the membrane and SERS signal amplification effect. This secreted protein analytical platform was further extended until a unique interfacial oriented aggregation (IOA) phenomenon was observed, in which the iMBs could accumulate to the cell membrane surface spontaneously, achieving a new interface ready for in-drop sandwich immunoassays. (683) The spontaneous collection of immuno-probes contributes dramatically to the SERS signal amplification according to the SERS hotspot effect. Besides, this IOA-based microdroplet-SERS platform eliminates the need for complex pretreatment relative to the cell membrane grafting strategy, resulting in minimal interference with cell metabolic function. The levels of three extracellular vesicle proteins (CD9, CD63, and FAK) related to metastasis in two breast cancer cell lines, and the single-cell SERS spectra were further analyzed and classified using supervised/unsupervised machine learning algorithms, acquiring feature subpopulations for different breast cancer subtypes. Following this strategy, a pH-responsive molecule (e.g., 4-mercaptopyridine) was used as a Raman reporter probe to decorate the immune-SERS nanotag to identify the extracellular microenvironmental pH along with the in-drop VEGF assay, (684) which will help understand the impacts of microenvironments on cell cytokines and vital for assessing early cancer diagnosis and prognosis.
Different from the secreted protein analysis, identifying small molecule metabolites is more challenging because there are no corresponding antibodies. A multifunctional magnetic/plasmonic (Fe3O4@AgNPs) composite nanotag was employed in a microdroplet-SERS platform, to realize the label-free in-drop SERS assays of various metabolites secreted by single cells. (685) This versatile magnetic SERS substrate was made by decorating magnetic microspheres (about 400 nm) with Ag NPs (about 30 nm), which could form multiscale hotspot structures due to the spontaneous aggregation in a droplet. Single-cell metabolites (pyruvate, lactic acid, and adenosine triphosphate) were directly adsorbed on the Fe3O4@Ag NPs (Figure 35), which significantly enhances the Raman signals of metabolites. Simultaneous monitoring of three cellular metabolites was realized according to their instinct Raman fingerprints.
Figure 35
Figure 35. Workflow of microfluidic droplet-SERS platform for single-cell encapsulation and simultaneous detection of three metabolites produced by a single cell. Reproduce with permission from ref (685).
The analysis of single-cell microRNA is essential for uncovering genetic-level cell heterogeneity. A high demand for tracing single-cell microRNAs is that they are highly similar and small in size and feature low-level expression. Sun and Xu et al. proposed the integration of SERS and fluorescence imaging technology into a microdroplet platform, enabling in situ, nondestructive, and highly sensitive detection of a small number of microRNA-21 in a single intact living cell. (686) A multifunctional plasmonic nanotag was created by decorating a Au NP with a fluorescent dye (ROX)-labeled DNA hairpin structure, which could lead to the dual-signal switching of fluorescence-off and SERS-on of ROX in response to microRNA-21 in droplets. The fluorescence-SERS dual-responsive strategy was able to mutually corroborate test results, improving the reliability of determining low-level microRNA expression. This advancement facilitates the exploration of single-cell miRNA-related biomedical studies.
8.9. Extracellular Vesicles SERS Monitoring and Diagnosis
Extracellular vehicles (EVs) have emerged as key biological messengers with diagnostic potential across various diseases, especially cancer. (687) In particular they may offer value as disease indicators in peripheral circulation (688) in even the earliest stages, including in multicancer detection. (445,689−691) Due to this potential, EV-SERS has been widely adopted in preclinical liquid biopsy diagnostics, where EVs are isolated from biological fluids such as blood, urine, or saliva and analyzed for early stage, noninvasive cancer diagnostics. (692) Compared to conventional omics-based molecular analysis, SERS offers a simple, quick approach to detect and profile these vesicles.
SERS substrates are typically used to enhance signals directly from EV biomarkers themselves. For example, nanoplasmonic-based detection can measure epidermal growth factor receptor (EGFR) mutations, common in several cancer types, from circulating EVs, which could be applied to screen for over 30 cancers with high sensitivity. (690) Another recent study applied EV-SERS for early stage cancer detection and tumor organ classification across six cancer types, with an impressive sensitivity of 90.2% and specificity of 94.4%.
Beyond direct disease detection, SERS has been increasingly applied to understand and assess the heterogeneity of EV subtypes, (693) for example, to distinguish melanoma EVs from red blood cell EVs, even at single vesicle resolution using only their intrinsic molecular profiles. (694) Machine learning-assisted classification has also been demonstrated to minimize the effects of lipoprotein contamination while still distinguishing between disease states, regardless of EV isolation method. (695)
Sensor architectures, especially ones tailored to the unique properties of EVs as a biomaterial, continue to improve as well. (696) While studies leverage simple surfaces of deposited nanoparticles as the primary materials for SERS-active surfaces, recent innovations beyond this include 3D plasmonic nanobowls, (693) hybrid nanoplasmonic scaffolds, (697) and nanobowtie-embedded microfluidic devices. (698) These substrates include the potential for analysis of EVs directly from biofluids. Another recent trend is the examination of the particular surface moieties of EVs in the near-field of the plasmonic “hotspots”. For example, enzymatic treatment of EV surfaces significantly altered SERS sensitivity, suggesting the importance of extraluminal domains in EV diagnostic platforms. (697) There has also recently been a surge in the analysis of extraluminal glycan moieties present at the EV surface. (699,700) For example, a recent study demonstrated a EV Glycan phenotype assay that utilized a SERS microfluidic platform, and completed the multiplex profiling of small EV glycans in nonsmall cell lung cancer in a clinical evaluation study on 40 patients. (701)
Yet, as a result of EV heterogeneity in size, origin, and cargo, their SERS spectra can be complex, such that differentiating between overlapping features is difficult. SERS signals are also sensitive to small fluctuations in environmental changes (temperature, pH, humidity) and inhomogeneities in the SERS substrates because of their manufacturing, all leading to variability in analyzed results. This complexity has led to advancements in data analytics to interpret results and extract meaningful conclusions, such as integrating machine learning techniques like supervised classification algorithms. The use of automated tools for processing has become more prevalent, driven by the need for more efficient and scalable data handling as the volume and complexity of SERS data increases. Several studies employ custom-built pipelines for EV spectral analysis, including advancements to more sophisticated model architectures like deep autoencoders. (702)
While EV-SERS research has found a strong foothold in cancer diagnostics, several gaps remain that must be addressed to further improve the utility for clinical applications. First, a lack of standardization across EV isolation techniques leads to inconsistencies in purity, which can affect downstream SERS analysis. Developing universal protocols for EV isolation is critical for achieving reproducible and reliable diagnostic results. (703) Second, the quantitative capabilities of EV-SERS are limited, an issue often exacerbated by the underlying heterogeneity of EVs and SERS substrates. Finally, as machine learning are becoming ubiquitous to enhance classification and analysis of complex SERS data sets, integrating models with increased explainability could greatly improve clinical adoption. (704)
Despite these hurdles, some emerging trends are likely to shape future research in this subfield. Chiefly, integration with microfluidics for real-time, on-chip analysis of EVs is an exciting direction, offering more streamlined and automated workflows with reduced sample handling and faster analysis times. (705) Several studies are also beginning to explore the integration of SERS with other omics techniques, such as proteomics, to provide a more comprehensive profile of EVs. (706) Finally, new interlaboratory studies to validate findings across unified protocols are also being carried out, which will certainly improve clinical potential. (707) In summary, continued advancements in standardization, quantitative capabilities, and integration with complementary technologies like microfluidics are essential for the broader clinical adoption of EVs.
8.10. SERS Endomicroscopic Imaging
SERS endoscopy is a method of integrating SERS imaging into the clinical endoscope, simultaneously provide biochemical information and anatomical tissue structure, allows real-time discrimination of pathologic changes on the internal surface of hollow organs. (708) The advantage of SERS endoscopy is the improved detection of small-sized pathologic changes that may not be visible with traditional white light endoscopy due to complex surface topography, mucosal folds, or visceral peristalsis in the intestinal tract cavity. (709) During the procedure, NPs targeting specific biomarkers, i.e., SERS nanotags equipped with a Raman reporter molecule and recognition element such as antibodies, are injected locally into the body during standard endoscopy. To minimize background signals and improve the accuracy of the analysis, unbound biomarker-targeted NPs are washed away. A spectrally imaging endoscope then emits laser light that induces Raman scattering, which is enhanced by the plasmonic effect on the metal surface of the NPs and produces spectral data. This data is used to determine the location and type of pathological cells based on the unique spectral fingerprint characteristic of bound SERS nanotags. (109,709)
The uniqueness of the spectral data obtained allows SERS endoscopy to be used for the most important steps in the diagnosis and treatment of cancer. Due to the high sensitivity and specificity of the method, several studies have demonstrated the ability of SERS endoscopy in identifying and classifying heterogeneous esophageal (710) and bladder (Figure 36a–c) (711) cancers by detecting biomarkers of carcinogenesis expressed on the cell surface. In addition, other studies have demonstrated the ability of enhanced SERS/SERRS signals in surgical navigation to delineate the boundaries of the pathologic focus (cancerous and precancerous tissue changes) and its complete resection in animal (709) and phantom (712) models. Early diagnosis and complete resection of the tumor are the most important factors affecting the patient’s survival and quality of life after treatment.
Figure 36
Figure 36. SERS imaging and endoscopic imaging of tumors. (a) Photograph and distribution of SERS nanotags related with s420-CA9, s421-IgG4, and s440-CD47 in bladder tumor. (b) Stem plot to illustrate tumor and normal tissue. (c) Binding of s421-IgG4 in normal and tumor tissue samples. Reproduced with permission from ref (711). (d) The estimation of the pH value employing a SERS-based endoscope equipped with a pH sensitive Raman reporter molecule in HeLa cells treated with cisplatin. (e) Variation of fluorescence intensity in HeLa cells treated with cisplatin and (f) the related fluorescence images. The incubation time with cisplatin was 0, 1, 3, 9, and 24 h. The scale bar in (f) represents 20 μm. Reproduced with permission from ref (713).
In addition, advanced technologies, such as confocal laser microendoscopy (CLE), allow for highly magnified cross-sectional images of the gastrointestinal epithelium and histologic diagnosis without biopsies. The principle of CLE is similar to SERS endoscopy, however, due to a focusing lens at the end of the optical fiber and a confocal aperture, the device registers the signal from the focus point in the tissue and makes possible the reconstruction of high quality microscopic images of the tissue. (709)
As promising tool in intracellular SERS endoscopy, Ag nanoneedles with atomically smooth surface properties having a length of several micrometers were developed as plasmonic waveguide structure to effectively compress the propagating plasmon modes at the sharp edges of these needles. (714) These nanofocusing capabilities are of high interest to record SERS spectra from a small volume compartment within the submicrometer range. As an alternative to Ag-based needle-like architectures, which are prone to oxidation processes, accompanied by a loss of their plasmonic field enhancement properties, Au NPs are applied to decorate nanofibers with a potential application in SERS-based cell endoscopic investigations. (715) Nanopipettes are modified with a block copolymer template to allow for tune the density of the attached Au NPs and their distance, i.e. gap size, for an efficient enhancement of the Raman signal from small cell compartments. The SERS activity of these Au NP-modified glass nanofibers could be even improved by a subsequent in situ growth of asymmetric Au NPs showing their potential in H2O2 and pH sensing. (716) In terms of cancer diagnosis, the change of the pH value of the intracellular environment could be used as an early predictor on single cell level. As an alternative, the density of hotspots along the SERS-active endoscopic probe was improved by the formation of Au nanostructures on smooth Ag nanowires. (717) Thus, by focusing the excitation laser on the Au-coated nanowires, SERS spectra of dyes labeling cell compartments were recorded within the nucleus and on the cell membrane in HeLa cells, with a high resolution and site specificity. Finally, Ag nanowires with a length of approximately 100 μm were fabricated being flexible and thin enough to penetrate through several cells and their membranes. (718) By doing so, SERS spectra could be recorded in 2D and 3D cell cultures and the SERS-active cell endoscope applied for investigating of cell compartments. By applying machine learning, distinguishing nucleic acid-rich and protein-rich regions was demonstrated. To sum up, the development of metallic nanowires or comparable SERS approaches for cell endoscopy illustrates their potential in the investigation of cell compartments, identifying molecular interactions in cells as well as dynamics with cells or cell cultures.
As an application scenario of SERS endoscopic approaches in cell investigations, the pH value was measured intracellular to investigate cytosolic and nuclear pH variations with high resolution and sensitivity as the change in pH value is important to shed light on physiological and pathological conditions. (713) Here, Au coated Ag nanowires were modified with 4-mercaptobenzoic acid, a pH sensitive Raman reporter molecule. The SERS-active endoscopic probe was incorporated into the nucleus as well as cytosol of HeLa cells and the variations in pH value were monitored in the presence of a hypoxia mimetic agent and an anticancer drug. In Figure 36d-f, the variations in pH value over time is illustrated for anticancer drug, i.e. cisplatin, treated HeLa cells. The advantage of endoscopic probes over classical SERS nanotags applied in intracellular pH sensing is associated with the limitations in applications of NPs which are trapped in endolysosomes. Thus, only endoscopic SERS approaches allow for site-specific investigations within different cell compartments and might be translated to other biological systems in future work. Moreover, a similar SERS endoscopic approach is applied to investigate the intracellular dynamics and distribution of drugs, using the example of doxorubicin, a chemotherapeutic drug, and its distribution in A549 cancer cells. (719) By penetrating Au-coated Ag nanowires into cell compartments, the localization of doxorubicin in the cell nucleus, the complexation of the drug molecule with other components and finally, the intercalation of doxorubicin with DNA was investigated. To be molecular-selective within the intracellular SERS measurements, Ag nanowires applied as endoscopic probe were coated with a metal–organic framework to selectively enrich the metabolite SN-38 of the common anticancer drug irinotecan toward the metallic surface. (720) Here, the conversion of the drug molecule could be detected within the cell for localization and as a function of time. All the presented examples underlie the potential of SERS endoscopic detection schemes in investigations of cell compartments to measure the pH value, drug or metabolite concentration site-specifically and shedding light into variations within cells due to outer influences such as the presence of a medical drug molecule or other agents. The current state of the art of further examples in SERS nanosensing employing endoscopic SERS approaches is beautifully summarized, (721) to which the interested reader is referred, to receive an overview about SERS nanoendoscopy and its application is opto physiological experiments accompanied by machine learning approaches to analyze large data sets. By penetrating SERS-active nanofibers into tissue or organs, the site specific release of biomarker or signaling molecules might be detectable with a high sensitivity, opening a new dimension of SERS-based approaches in medical and biological research. (722)
Advantages and features of SERS (nano)endoscopy has excellent prospects for clinical application, creating competition with already used gold standards diagnostics. We expect that soon SERS (nano)endoscopy may find its place in noninvasive diagnosis of cancer of the urinary, gastrointestinal and respiratory systems, and show excellent results in the navigation and classification of changes in tissues in the nervous system under different pathological conditions. However, further research is needed to optimize and develop advanced fiber optic probes, increase SERS NP sensitivity and expand clinical applications for wider deployment and greater diagnostic accuracy.
8.11. Deep Raman Spectroscopy for In Vivo Detection and Imaging I: SESORS
Noninvasive detection of in vivo lesions, such as tumors, is of great significance in biomedicine and clinic. Due to the strong scattering and absorption of photons in biological tissues, the typical detection of backscattering Raman spectroscopy is limited to hundreds of microns to a few millimeters. (218) Surface enhanced spatially offset Raman spectroscopy (SESORS) (723,724) is a potent technique well suited to biomedical and clinical applications (Figure 37a). The method combines the unique power of SERS to probe low concentration bioanalytes, through its high sensitivity and chemical and biological specificity, with the noninvasive probing capability of spatially offset Raman spectroscopy (SORS). (725) It enables the probing of SERS targets deep inside biological tissues.
Figure 37
Figure 37. Concepts and applications of deep Raman spectroscopy. (a) SESORS concept: SERS signal is recovered noninvasively using SORS concept in which the illumination and collection zones are spatially separated from each other on sample surface. SETRS concept: The configuration separates the excitation laser and the Raman detector on opposite sides of the sample to collect the SERS signals. (b) SETRS detections through 7.1 cm-thick biological tissues. Reproduced from ref (743). (c) SETRS detections through 14 cm thick ex vivo porcine tissues. Reproduced from ref (226). (d) The home-built TRS system with ultrabright SERS nanotags, a fiber-optic Raman probe, a 785 nm laser with a diffuse beam. Adapted from ref (226). (e) Scheme of ratiometric Raman spectroscopy to calculate the depth of SERS in biological tissues. (f) Noninvasive in vivo detection and localization of 6.5 mm deep SLNs in rats using ratiometric TRS. Adapted from ref (747). (g) Tomographic TRS enables the rapid three-dimensional localization of SERS nanotags in thick tissues. Adapted from ref (749). (h) Raman spectral projection tomography system to the imaging and visualization of Raman molecules in phantoms. Reproduced from ref (750).
SORS is a method based on illuminating the sample surface with laser light at a given spatial location and detecting Raman signal at a different, spatially offset position. The separation of the two zones from each other is termed spatial offset (Δs). The larger the spatial offset, the deeper the probed zone: this is due to the statistical nature of photon diffusion in tissue favoring deeper paths to near surface ones as the proximity of surface-air interface leads to a major loss of photons that tend to leak across the boundary. The dependence of probed depth on the spatial offset was studied by Mosca et al. (726) There are multiple illumination and collection geometries one could utilize (727) ranging from a point illumination one to probing on the opposite side of the sample, named as transmission Raman spectroscopy (TRS), which will be elaborated in the next section. Inverse SORS presents another very attractive option for biological and clinical applications. In this configuration, the laser light illuminates the sample in a ring pattern and Raman light is collected from the center of the ring, with the radius of the ring representing the spatial offset. This configuration enables spreading of the light across much wider area compared, for example, to a point illumination. This is highly beneficial in biological applications in vivo where safety laser intensity limits need to be adhered to. The SORS technique is applicable to both sensing native matrix Raman signals as well as SERS signals, known as SESORS.
There are numerous biological applications of SESORS under investigations. For example, the technique is under development for noninvasively detecting neurotransmitters. Here, the detection of clinically relevant levels through the skull have been recently demonstrated ex vivo. (728) SESORS was also applied to detecting subsurface cancer in the brain tissue of mice. (729) This study represented the first use of SESORS in vivo in cancer diagnosis.
Apart from detecting the presence of SERS NPs, one can also sense their local environment. For example SESORS was shown to be capable of monitoring noninvasively local pH levels. (730,731) This is beneficial in cancer diagnosis as the cancer microenvironment typically exhibits lower pH levels to those of healthy tissue, due to the Warburg effect. (732) SESORS can also sense physical properties such as temperature at depth using both the Stokes and anti-Stokes spectral regions. (733) Such thermal reading is not possible using traditional thermometry. This property is particularly attractive in photothermal treatment of cancers where it can provide unique temperature feedback on the temperature of lesion at depth to enable the therapy optimization for highest efficacy while minimizing the collateral damage to healthy tissue. Other SESORS applications include the localization of a cancer lesion, including the detection of bulk tumor, subsequent delineation of tumor margins, and the identification of a deeper secondary region of interest. (734) The lateral position of the lesion can be determined by mapping signals on sample surface and its depth by monitoring spectral changes to the detected SESORS signals. (735−738)
Recently, SESORS was also combined with ultrasound to further boost its sensitivity. (739) This permits lower detection levels to be achievable, opening prospects for detecting diseased conditions at still earlier stages and with less NPs, the latter presenting lower toxicity risks to the patient. In this concept, ultrasound is used to induce an intensity change to SERS signal and SESORS measurement is performed before and after the application of ultrasound yielding, after their subtraction, a higher contrast signature of NPs by effectively eliminating tissue matrix signal and any associated artifacts.
We should note that, although the signal detection is noninvasive, the delivery of SERS NPs to the target zone is, naturally, required. This can be accomplished, for example, by intravenous delivery or by direct injection into the probed site. The issue of potential toxicity of SERS NPs can be also addressed by developing a new class of Au NPs that disintegrate inside body after their use into smaller entities (e.g., sub 5 nm) for safe excretion from body. (740,741) Although the SERS enhancement of the self-disintegrating NPs is still not as high as with traditional SERS, this is anticipated to further improve with ongoing research into these concepts in the coming years.
8.12. Deep Raman Spectroscopy for In Vivo Detection and Imaging II: SETRS
Surface-enhanced transmission Raman spectroscopy (SETRS) is an advanced technique derived from TRS. As previously mentioned, in TRS the excitation laser and the Raman detection zones are on the opposite sides of the sample. Along with SORS, TRS is often classified as a “deep Raman spectroscopy” method. The TRS configuration significantly suppresses background signals from superficial tissues near the excitation site and enhances the detection of deep-embedded targets in scattering media. This approach has been widely utilized in industrial applications, such as pharmaceutical drug monitoring. (742) From a biological standpoint, TRS stands out as a valuable variant of SORS, particularly in cases where the anatomical site of interest is accessible from both sides of the sample and falls within a suitable tissue thickness range. Compared to conventional SORS, (727) TRS offers relatively uniform sensitivity across depths, making it well-suited for screening analytes at unknown depths.
When combined with surface-enhanced Raman scattering (SERS) nanotags, SETRS offers significant advantages in the biomedical detection of deeply embedded lesions. In standard TRS measurements, detection performance depends on several factors, including tissue scattering and absorption properties, as well as the brightness of the SERS nanotags, the depth of the buried lesion, and the overall tissue thickness. Zhang et al. conducted theoretical calculations on Raman photon propagation for in vivo TRS experiments, analyzing the effect of these parameters. (226) They found that the most effective way to increase detection depth and tissue penetration is by using brighter SERS nanotags; In addition, due to the strong scattering and diffusion of laser light within biological tissues, both focused and diffuse beams (with equal power) demonstrate similar detection capabilities. (226) This provides new insights for the photosafe TRS detection, as the diffuse beam with a larger spot size can significantly reduce power density to below the clinical maximum permissible exposure (MPE) limits.
SETRS has been shown to detect SERS NPs in biological tissues at depths of 7 to 14 cm (Figure 37b, c), (226,743) far exceeding the typical tissue thickness (a few millimeters) achieved using conventional backscattering mode. (218,712) These depths are comparable to those achieved by fluorescence molecular tomograph using multiple coupled laser-probe systems. For example, Zhang et al. developed a home-built SETRS system featuring ultrabright SERS nanotags, (744) a micro-SORS fiber-optic Raman probe with deeper light detection ability, (712,745) and a 785 nm laser with a large beam radius of 0.85 cm (yielding a low power density of 0.264 W/cm2, below the MPE of 0.296 W/cm2) (Figure 37d). (226) Using this system, they achieved safe detection of SERS nanotags buried in 14 cm of ex vivo tissue (Figure 37c) and noninvasive in vivo detection of lesion phantoms in live, fur-covered mice with the penetration thickness of 1.5 cm. (226) A more recent study utilized this TRS setup for in vivo detection in a live rat whose total thickness was of 2.6 cm. (197)
In addition to detection, localization of hidden lesions is also crucial. Zhang et al. demonstrated a linear relationship between the natural logarithm of the intensity ratio of two Raman peaks and lesion depth, allowing depth prediction using Raman peak ratios, named as ratiometric TRS (Figure 37e). (746) By leveraging multiple Raman peaks, depth prediction in heterogeneous tissues can be achieved by integrating information from multiple peak pairs, for example, the accurate depth prediction of lesions in 5 cm thick heterogeneous tissues (comprising skin, fat, and muscle) was reported using ratiometric TRS, with a root mean squared error (RMSE) as low as 8.35%. (746) Wu et al. further applied ratiometric TRS to live rat models, using the popliteal sentinel lymph nodes (SLNs) as deep lesions (Figure 37f). (747) They successfully conducted perioperative surgery for SLNs, including preoperative noninvasive detection, intraoperative localization, and postoperative examination. In vivo detection and accurate localization of 6.5 mm deep SLNs in rats were performed using TRS and SERS nanotags under clinically safe laser irradiation (0.21 W/cm2). (747) This study was the first to demonstrate the localization and perioperative surgery guidance of deep lesions in a live animal model using SETRS. Even if in complex in vivo environments containing heterogeneous tissues and blood flow, SETRS exhibits excellent detection depth and localization accuracy, highlighting its potential for clinical applications.
An exciting future direction for SETRS would be the development of 3D imaging or reconstruction of target lesion structures. The ability to image 3D tissues using Raman labels or label-free molecular contrast is highly valuable for biomedical research. This opens the possibility of practical small-animal imaging systems, similar to established techniques like fluorescence molecular tomography or diffuse optical tomography. Raman tomography was previously reported by using multiple laser-receptor pairs in a ring-arranged fiber setting. (748) By using transmission configuration, a two-step TRS tomography was reported to localize SERS nanotags in a two-dimensional plane (Figure 37g, i), enabling rapid three-dimensional localization of one or multiple SERS nanotags in 4.5 cm thick ex vivo tissues (Figure 37g, ii). (749) Stepula et al. constructed a Raman spectral projection tomography system based on transmission geometry, combined with a computational pipeline for multivariate reconstruction to extract label-free spatial molecular information from Raman projection data (Figure 37h, i). (750) They demonstrated the imaging and visualization of Raman molecules in phantoms (Figure 37h, ii), as well as the extracellular matrix heterogeneities in living tissue-engineered constructs. (750) Future advancements in SETRS tomography could integrate topographic surface Raman imaging to improve the localization of SERS NP-targeted lesions or combine Raman imaging with histological analyses. (751)
Overall, the rapid development of deep Raman techniques, including SORS and TRS, is closing the gap between ex vivo demonstrations and in vivo biomedical applications. To facilitate the clinical translation of SETRS, its efficacy and safety should first be validated in preclinical large animal models, and the detection systems are anticipated to be optimized to be more feasible, user-friendly, and accessible for clinical practitioners.
9. Conclusion and Perspective
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For perspective and outlook, there are a number of emerging trends and opportunities. One is to exploit the intrinsically label-free capabilities of SERS to detect and differentiate complex biomedical biomarkers such as nucleic acid, protein and metabolite molecules in blood and tissue biopsies, to be aided by artificial intelligence or single-molecule counting as enabled by digital SERS. Also, there is a great promise in translating biocompatible SERS-encoded nanotags for in vivo tumor imaging and spectroscopy-guided surgery. Here, an urgent need is to develop sensitive and compact devices of noninvasive, rapid and high-resolution spectroscopic measurements at deep tissue penetration.
There are also fundamental or intrinsic challenges in developing SERS for medical applications. First, since a wavelength-resolved Raman spectrum is acquired at each spatial point, SERS is excellent for zoomed-in measurements at specific tissue sites or locations. This limitation can be overcome or mitigated by combining Raman spectroscopy with wide-field imaging modalities (such as CT, MRI, PET, ultrasound, photoacoustics, or fluorescence) that provide anatomical, functional, and molecular information with limited sensitivity or specificity. In this case, the addition of SERS would provide ultrahigh sensitivity and specificity, even at the level of single tumor cells or single molecules. Another fundamental challenge is the long-term fate in vivo and safety of Au NPs, which are largely not biodegradable. Upon rapid uptake by the liver, spleen, and other reticuloendothelial system (RES) organs, these particles are often retained in the body for very long periods of time (months to years). The developments in “excretable” Au nanoclusters look promising, but the associated materials used for surface coating and tagging still need to be systematically evaluated for long-term clinical safety and efficacy.
9.1. Translation and Commercialization of SERS
Compared to in vivo use that is limited by the strict regulations, translation toward SERS POCT application is more promising. This advancement hinges on portable and user-friendly instruments, devices, and detection systems. For example, SERS-based LFAs have shown significant promise in diagnostics, as they offer superior sensitivity compared to traditional colorimetric LFAs. (752,753) Although commercially available LFAs still predominantly rely on colorimetric or fluorescent methods due to challenges in reproducibility, stability, and cost-efficiency that currently limit SERS LFAs, SERS stands out with its multiplexing capability. This enables simultaneous detection of multiple biomarkers on a single test strip. This is particularly advantageous for scenarios such as detecting multiple bacteria, (752) pathogens, (754) or cardiac markers. (755) SERS can also complement fluorescence or colorimetric methods to improve detection accuracy. (756) Also, achieving widespread adoption will require the development of low-cost, miniaturized Raman systems for diverse healthcare environments. Transitioning SERS from laboratory setups to portable hand-held devices is essential for commercialization, especially in resource-limited environments where traditional diagnostics are impractical.
One of the challenges in SERS translation is the reproducibility and standardization of plasmonic substrates, which are critical for consistent SERS signals. Variability in signal enhancement due to differences in substrate quality, sample preparation, or environmental factors undermines clinical reliability. Advances in substrate fabrication, including self-assembled NP arrays, 3D scaffolds, and MOFs, are expected to provide improved uniformity and reproducibility. The digital (nano)colloid-enhanced Raman spectroscopy (as mentioned in Section 7.2) was proposed for the reproducible, quantitative detection of a wide range of target molecules at low concentrations; this shows promise for application to various metabolites related to human health. In a recent study, plasmonic metasurfaces, consisting of alternately stacked metal-dielectric pyramidal meta-atoms, were proposed as a strategy to deal with the trade-off between “reproducibility” and “enhancement”. (757) The nanomechanical perturbations of this metasurface are harnessed and transduced in the form of SERS frequency shifts that are not directly affected by the SERS uncertainty principle, thus enhancing the signal reproducibility.
Another issue is the long-term stability of plasmonic substrates during storage and transport. Spherical substrates are relatively stable, whereas irregularly shaped NPs (e.g., nanostar or nanorod) may undergo shape changes over time, significantly altering their optical properties. Optimization of surface coatings, such as long-chain stabilizers or biomimetic membrane coatings, is expected to better preserve particle morphology and optical properties. In a recent work, the highly dispersible Au nanorod powder was reported using an octadecyltrimethylammonium bromide (C18TAB)-assisted lyophilization method, which preserved the optical and chemical sensing properties of NPs for over 4 months. (758) This work marks an effective strategy to advance the use of nanorods as standard analytical reagents.
9.2. In Vivo Deep Sensing: Spontaneous Raman versus SERS
As reviewed in this article, in vivo deep sensing has made substantial strides in recent years and shows promise as a detection method capable of penetrating human tissue thickness. However, a significant challenge remains to be the safety of SERS nanotags and effective delivery of them to the target lesion site. NPs must be precisely delivered to the desired location within the body. This often involves sophisticated delivery mechanisms, such as systemic injections or localized administration, to ensure the probes reach the target tissues without being prematurely cleared by the immune system. Currently, local injections, such as those used for sentinel lymph node imaging, offer a potential breakthrough, as they limit the systemic circulation of NPs. (263,759) Achieving nontoxic, biodegradable, and easily clearable SERS nanotags without adverse effects remains critical for clinical translation. In a recent study, a series of Raman-active nanodots that exhibit ultrabrightness and compact sizes (∼20 nm) was developed. (760) These particles yield high Raman emission through the molecular stacking inside the polymer NPs, instead of using metal substrates; they are thus promising to offer better biocompatibility than metallic SERS NPs.
In addition, the integration of SORS/TRS with SERS endoscopy is a promising avenue for deep tissue imaging, as endoscopy reduces the tissue thickness through which light must pass, allowing signals to be transmitted more efficiently from inside the body. This approach is particularly well suited for hollow organs such as the gastrointestinal (GI) tract and bronchi. Further research is needed to optimize fiber optic probes and increase the sensitivity of SERS NPs. For example, the use of a miniaturized Raman device inserted into the ex vivo pig bronchoscope channels has demonstrated the detection of SERS nanotags through a bronchial wall (approaching the fourth generation airway) and adjunct lung tissue. (712) In an anticipated SORS/TRS setup, the diffuse laser could illuminate the skin from the outside, and the endoscopic probe could collect the signal from the inside, expanding the detection area with improved detection depth for broader use.
Alternatively, spontaneous Raman spectroscopy detection of intrinsic biomolecules using deep Raman spectroscopy has great potential. Noninvasive blood glucose detection using the SORS configuration has been successfully demonstrated on pig ears. (761) To further enhance the tissue penetration depth of SORS/TRS, the use of tissue clearing agents is expected. Recently, Ou et al. reported an inspiring study that strongly absorbing molecules (such as tartrazine) can achieve optical transparency in living animals because these molecules dissolving in water can change the refractive index of the aqueous medium to match that of high-index tissue components such as lipids. (762) This transparency process is reversible and exhibits excellent biocompatibility. The search for similar optical clearing agents with powerful and prolonged efficacy could significantly advance the in vivo application of SORS/TRS.
9.3. Dual-Modal SERS and Fluorescence
A key innovation that holds significant promise for both research and commercial applications is the development of dual-modal systems that combine SERS with fluorescence imaging. Fluorescence is widely used in biological imaging due to its high sensitivity, fast acquisition times, and compatibility with a range of biomolecules. However, it often suffers from issues such as photobleaching and background autofluorescence, particularly in complex biological samples. By integrating SERS, which offers high specificity and resistance to photobleaching, these dual-modal systems can overcome the limitations inherent in fluorescence. Dual-modal SERS-fluorescence platforms offer complementary information: fluorescence provides rapid localization, while SERS offers molecularly specific identification. (763)
Among various possible benefits of combining fluorescence and SERS, the most appealing is perhaps based on the consideration that fluorescence transduction is the most widely employed in biology and medicine, which could facilitate in the future the translation of SERS to the clinic. By leveraging dual modality fluorescence-SERS sensors, an initial introduction to the medical and biological fields can first be proposed employing fluorescence, to then shift to the use of SERS as well, once the method can be validated by these communities.
The regulatory landscape for SERS technologies remains an ongoing challenge. Dual-modal SERS-fluorescence systems, however, may ease this transition by building on the well-established clinical use of fluorescence imaging. Incorporating SERS as a supplementary modality can be framed as an enhancement to existing diagnostic techniques, potentially shortening the regulatory approval process.
9.4. AI for SERS in Biomedicine
The rapid advancement of AI in image analysis and natural language processing is also revolutionizing the field of SERS. (445,764−766) We believe AI holds tremendous promise in biomedicine, including design of SERS chip, data analysis, and disease diagnosis. AI optimizes processes such as NP functionalization, spectral preprocessing, and sample pretreatment, reducing trial and error and enabling precise molecular analysis even in complex biological matrices. Moreover, the integration of AI with SERS facilitates high-throughput screening of multiple biomarkers, making diagnostics more accurate and responsive. (764)
With the growing amount of SERS data, one of the important directions would be the extraction of key latent features from massive data sets to facilitate the reverse optimization of SERS detection and analysis. The intensity and peak shape of SERS spectra can be influenced by a multitude of known and unknown factors in complex scenarios. (767−769) It is therefore in need to delve deeper into the nonlinear behaviors of SERS by harnessing the power of explainable AI. (770,771) Particularly, since the conventional data-driven AI can approximate but fails to explicitly tell the underlying physics of SERS, the development of mathematical knowledge-driven AI models is beneficial to fill the gap between the interpretable machine learning results and the actual SERS data.
Despite these advancements, it remains demanding in data quality control and universal standardization across instruments, sample types, and institutions. Additionally, ethical issues are increasingly recognized as central to the responsible adoption of AI particularly in clinical settings. Safeguarding patient privacy, mitigating biases, ensuring transparency, and adhering to regulatory frameworks like general data protection regulation (GDPR) are critical. By prioritizing these ethical considerations, AI-SERS technologies are poised to transition from laboratory proof-of-concepts to transformative clinical tools, advancing diagnostics while upholding equity, accountability, and trust.
Author Information
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- Xing Yi Ling - School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 21 Nanyang Link, Singapore 637371; Key Laboratory of Synthetic and Biological Colloids, Ministry of Education, International Joint Research Laboratory for Nano Energy Composites, School of Chemical and Material Engineering, Jiangnan University, Wuxi 214122, P. R. China;
https://orcid.org/0000-0001-5495-6428;
- Jian Ye - Sixth People’s Hospital, School of Medicine & School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, P. R. China;https://orcid.org/0000-0002-8101-8362;
- Linley Li Lin - Sixth People’s Hospital, School of Medicine & School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, P. R. China;https://orcid.org/0000-0002-8079-5768
- Ramon Alvarez-Puebla - Departamento de Química Física e Inorganica, Universitat Rovira i Virgili, Tarragona 43007, Spain; ICREA-Institució Catalana de Recerca i Estudis Avançats, Barcelona 08010, Spain;https://orcid.org/0000-0003-4770-5756
- Luis M. Liz-Marzán - CIC biomaGUNE, Basque Research and Technology Alliance (BRTA), Donostia-San Sebastián 20014, Spain; Ikerbasque, Basque Foundation for Science, University of Santiago de nCompostela, Bilbao 48013, Spain; Centro de Investigación Cooperativa en Red, Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Donostia-San Sebastián 20014, Spain; Cinbio, University of Vigo, Vigo 36310, Spain;https://orcid.org/0000-0002-6647-1353
- Matt Trau - Centre for Personalized Nanomedicine, Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, QLD 4072, Australia; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia;https://orcid.org/0000-0001-5516-1280
- Jing Wang - Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, Fujian Provincial Key Laboratory of Photonics Technology, Fujian Normal University, Fuzhou 350117, China;https://orcid.org/0000-0001-6080-7998
- Laura Fabris - Department of Applied Science and Technology, Politecnico di Torino Corso Duca degli Abruzzi 24, 10129 Torino, Italy;https://orcid.org/0000-0002-7089-5175
- Xiang Wang - State Key Laboratory of Physical Chemistry of Solid Surfaces, Collaborative Innovation Center of Chemistry for Energy Materials (iChEM), Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM), Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China;https://orcid.org/0000-0003-1937-0725
- Guokun Liu - State Key Laboratory of Marine Environmental Science, Fujian Provincial Key Laboratory for Coastal Ecology and Environmental Studies, Center for Marine Environmental Chemistry and Toxicology, College of the Environment and Ecology, Xiamen University, Xiamen 361005, China;https://orcid.org/0000-0003-2501-7178
- Shuping Xu - State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun 130012, PR China;https://orcid.org/0000-0002-6216-6175
- Xiao Xia Han - State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun 130012, PR China;https://orcid.org/0000-0002-0544-4351
- Liangbao Yang - Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230031, P. R. China; Department of Pharmacy, Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei, Anhui 230031, P. R. China;https://orcid.org/0000-0002-6559-6947
- Shikuan Yang - School of Materials Science and Engineering, Zhejiang University, Hangzhou 310027, P. R. China;https://orcid.org/0000-0001-6662-3057
- Yikai Xu - Key Laboratory for Advanced Materials and Feringa Nobel Prize Scientist Joint Research Center, Frontiers Science Center for Materiobiology and Dynamic Chemistry, School of Chemistry and Molecular Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, P. R. China;https://orcid.org/0000-0003-3881-8871
- Chunchun Li - School of Materials Science and Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, P. R. China;https://orcid.org/0000-0001-9501-0313
- Shao-Chuang Liu - Molecular Sensing and Imaging Center, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, P. R. China;https://orcid.org/0000-0002-1010-2321
- Jian-An Huang - Research Unit of Health Sciences and Technology, Faculty of Medicine, University of Oulu, Aapistie 5 A, 90220 Oulu, Finland; Research Unit of Disease Networks, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Aapistie 5 A, 90220 Oulu, Finland; Biocenter Oulu, University of Oulu, Aapistie 5 A, 90220 Oulu, Finland;https://orcid.org/0000-0002-6564-5972
- Indrajit Srivastava - Department of Mechanical Engineering, Texas Tech University, Lubbock, Texas 79409, United States; Texas Center for Comparative Cancer Research (TC3R), Amarillo, Texas 79106, United States;https://orcid.org/0000-0002-6864-0202
- Ming Li - School of Materials Science and Engineering, Central South University, Changsha, Hunan 410083, China;https://orcid.org/0000-0002-2289-0222
- Limei Tian - Department of Biomedical Engineering, and Center for Remote Health Technologies and Systems Texas A&M University, College Station, Texas 77843, United States;https://orcid.org/0000-0002-1931-8567
- Pavel Matousek - Central Laser Facility, Research Complex at Harwell, STFC Rutherford Appleton Laboratory, UKRI, Harwell Campus, Oxfordshire OX11 0QX, United Kingdom; Department of Physics and Astronomy, University of Exeter, Exeter EX4 4QL, United Kingdom;https://orcid.org/0000-0003-0912-5339
- Nicholas Stone - Department of Physics and Astronomy, University of Exeter, Exeter EX4 4QL, United Kingdom;https://orcid.org/0000-0001-5603-3731
- Randy P. Carney - Department of Biomedical Engineering, University of California, Davis, California 95616, United States;https://orcid.org/0000-0001-8193-1664
- Wei Ji - College of Chemistry, Chemical Engineering and Resource Utilization, Northeast Forestry University, Harbin 145040, China;https://orcid.org/0000-0001-6391-9768
- Wei Song - State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun 130012, PR China;https://orcid.org/0000-0001-9814-419X
- Zhou Chen - Sixth People’s Hospital, School of Medicine & School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, P. R. China;https://orcid.org/0000-0002-3018-8169
- Malou Henriksen-Lacey - CIC biomaGUNE, Basque Research and Technology Alliance (BRTA), Donostia-San Sebastián 20014, Spain; Centro de Investigación Cooperativa en Red, Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Donostia-San Sebastián 20014, Spain;https://orcid.org/0000-0003-3544-5846
- Hao Ma - State Key Laboratory of Physical Chemistry of Solid Surfaces, Collaborative Innovation Center of Chemistry for Energy Materials (iChEM), Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM), Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China;https://orcid.org/0000-0001-8341-4003
- Sara Mosca - Central Laser Facility, Research Complex at Harwell, STFC Rutherford Appleton Laboratory, UKRI, Harwell Campus, Oxfordshire OX11 0QX, United Kingdom;https://orcid.org/0000-0001-9479-5614
- Benjamin Gardner - Department of Physics and Astronomy, University of Exeter, Exeter EX4 4QL, United Kingdom;https://orcid.org/0000-0002-7223-9585
- Yi-Tao Long - Molecular Sensing and Imaging Center, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, P. R. China;https://orcid.org/0000-0003-2571-7457
- Juergen Popp - Leibniz Institute of Photonic Technology, Member of Leibniz Health Technologies, Member of the Leibniz Centre for Photonics in Infection Research (LPI), Albert-Einstein-Straße 9, 07745 Jena, Germany; Institute of Physical Chemistry (IPC) and Abbe Center of Photonics (ACP), Friedrich Schiller University Jena, Member of the Leibniz Centre for Photonics in Infection Research (LPI), Helmholtzweg 4, 07743 Jena, Germany;https://orcid.org/0000-0003-4257-593X
- Bin Ren - State Key Laboratory of Physical Chemistry of Solid Surfaces, Collaborative Innovation Center of Chemistry for Energy Materials (iChEM), Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM), Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China;https://orcid.org/0000-0002-9821-5864
- Shuming Nie - Department of Bioengineering, University of Illinois at Urbana−Champaign, 1406 W. Green Street, Urbana, Illinois 61801, United States;https://orcid.org/0000-0002-7328-1144
- Bing Zhao - State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun 130012, PR China;https://orcid.org/0000-0002-0044-9743
Acknowledgments
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We thank Qing He, Yaxuan Lu, and Han Shen for their help in preparing and organizing the manuscript. The authors are thankful for the following grants. Jian Ye, Linley Li Lin, and Xinyuan Bi: National Key Research and Development Program of China (No. 2024YFF1502600), National Natural Science Foundation of China (Nos. 82272054, 82372016, 623B2070), Science and Technology Commission of Shanghai Municipality (No. 24DIPA00300), Shanghai Jiao Tong University (Nos. YG2024LC09, YG2024QNA15). Aiguo Shen: National Natural Science Foundation of China (Nos. 22074109, 2247040793). Ramon Alvarez-Puebla: Projects PID2020-120306RB-I00 and PID2020-113704RB-I00 (funded by MCIN/AEI/10.13039/501100011033), PDC2021-121787-I00 (funded by MCIN/AEI/10.13039/501100011033 and European Union Next Generation EU/PRTR), 2017SGR883 (funded by Generalitat de Cataluña), and 2021PFR-URV-B2-02 (funded by Universitat Rovira i Virgili). Xing Yi Ling: Singapore National Research Foundation Investigatorship (NRF-NRFI08-2022-0011), Competitive Research Programme (NRF-CRP26-2021-0002). Limei Tian: Funding from the National Science Foundation (No. 1648451) and the National Institutes of Health (No. R35 GM147568). Luis M. Liz-Marzán: European Research Council (ERC Advanced Grant 787510, 4DbioSERS). Chunchun Li: Shanghai Pujiang Program (No. 23PJ1409000). Shuping Xu: National Natural Science Foundation of China (No. 22373041), Science and Technology Development Program Projects of Jilin Province (No. 20220101046JC). Jian-An Huang: Academy Research Fellow project, TwoPoreProSeq (No. 347652), and DigiHealth project (No. 326291), a strategic profiling project at the University of Oulu that is supported by the Academy of Finland and the University of Oulu. Xiao Xia Han and Bing Zhao: National Natural Science Foundation of China (Nos. 22073014, 22074051). Yikai Xu: Fundamental Research Funds for the Central Universities (No. JKJ01231812). Jinqing Huang: Research Grant Council of Hong Kong (No. 16309721). Yitao Long: National Natural Science Foundation of China (No. 2220407). Matt Trau: ARC Australian Laureate Fellowship (No. FL220100059). Jing Wang: National Natural Science Foundation of China (No. 12074069). Liangbao Yang: National Natural Science Foundation of China (No. 22474143). Guokun Liu: National Natural Science Foundation of China (No. 22272139). Pavel Matousek: “RaNT: Raman Nanotheranostics” EPSRC Programme Grant (EP/R020965/1) and EP/P012442/1. Randy P. Carney: National Institutes of Health (NIH) R01CA241666. Jurgen Popp: The Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) (No. 465289819).
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- 3Ervin, K. M.; Koglin, E.; Sequaris, J. M.; Valenta, P.; Nürnberg, H. W. Surface enhanced Raman spectra of nucleic acid components adsorbed at a silver electrode. Journal of Electroanalytical Chemistry and Interfacial Electrochemistry 1980, 114, 179– 194, DOI: 10.1016/S0022-0728(80)80446-3Google Scholar3Surface enhanced Raman spectra of nucleic acid components adsorbed at a silver electrodeErvin, K. M.; Koglin, E.; Sequaris, J. M.; Valenta, P.; Nuernberg, H. W.Journal of Electroanalytical Chemistry and Interfacial Electrochemistry (1980), 114 (2), 179-94CODEN: JEIEBC; ISSN:0022-0728.High-resoln. vibrational spectra of nucleic acid components adsorbed on Ag electrode were obtained using a spectroelectrochem. method based on the large-intensity enhancement for Raman scattering at electrode surfaces. The laser surface Raman spectra of purine, adenine, adenosine, deoxyadenosine, adenine mononucleotides, adenylyl-3',5'-adenosine and polyriboadenylic acid were recorded in the range of 150-3500 cm-1. The intensities of the vibrational bands were highly dependent upon the electrochem. prepn. of the electrode, the applied potential and the nature of the adsorbate species. High-intensity spectra in rather dil. bulk solns. were obtained. The phosphate derivs. of adenosine exhibited strongly enhanced Raman scattering. Spectral band frequencies corresponded closely with normal Raman spectra of these mols. in soln. The adenine ring breathing mode at 740 cm-1 and the adenine ring skeletal vibration at 1335 cm-1 produced prominent Raman scattering. A strong band at about 240 cm-1 for the adenine mononucleotides was attributed to Ag/adsorbed phosphate group vibrations.
- 4Koglin, E.; Séquaris, J. M.; Valenta, P. Surface enhanced raman spectroscopy of nucleic acid bases on Ag electrodes. J. Mol. Struct. 1982, 79, 185– 189, DOI: 10.1016/0022-2860(82)85050-3Google ScholarThere is no corresponding record for this reference.
- 5Cotton, T. M.; Schultz, S. G.; Van Duyne, R. P. Surface-enhanced resonance Raman scattering from cytochrome c and myoglobin adsorbed on a silver electrode. J. Am. Chem. Soc. 1980, 102, 7960– 7962, DOI: 10.1021/ja00547a036Google Scholar5Surface-enhanced resonance Raman scattering from cytochrome c and myoglobin adsorbed on a silver electrodeCotton, Therese M.; Schultz, Steven G.; Van Duyne, Richard P.Journal of the American Chemical Society (1980), 102 (27), 7960-2CODEN: JACSAT; ISSN:0002-7863.Surface enhanced resonance Raman spectra are reported for cytochrome c and myoglobin spontaneously adsorbed from micromolar solns. onto a Ag electrode. The enhancement factor is estd. to be ∼105 above that produced by the conventional resonance Raman effect. The signal intensities in both proteins are anodization and potential dependent. All resonance Raman bands are depolarized (ρ ≥0.5) on the electrode. These observations are consistent with an enhancement mechanism similar to that underlying the surface enhanced Raman (SER) effect in small mols. adsorbed on Ag electrodes. Both cytochrome and myoglobin undergo potential dependent redox changes at the electrode. These results clearly indicate the great potential of combined SER and resonance Raman spectroscopy for bioanal. applications such as the study of: (1) rare, difficult to isolate, or highly dil. prepns. and (2) redox active biomols. adsorbed on electrodes.
- 6Cotton, T. M.; Kim, J.-H.; Chumanov, G. D. Application of surface-enhanced Raman spectroscopy to biological systems. J. Raman Spectrosc. 1991, 22, 729– 742, DOI: 10.1002/jrs.1250221203Google ScholarThere is no corresponding record for this reference.
- 7Ozaki, Y. Medical Application of Raman Spectroscopy. Appl. Spectrosc. Rev. 1988, 24, 259– 312, DOI: 10.1080/05704928808060459Google ScholarThere is no corresponding record for this reference.
- 8Nie, S.; Emory, S. R. Probing Single Molecules and Single Nanoparticles by Surface-Enhanced Raman Scattering. Science 1997, 275, 1102– 1106, DOI: 10.1126/science.275.5303.1102Google Scholar8Probing single molecules and single nanoparticles by surface-enhanced Raman scatteringNie, Shuming; Emory, Steven R.Science (Washington, D. C.) (1997), 275 (5303), 1102-1106CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)Optical detection and spectroscopy of single mols. and single nanoparticles were achieved at room temp. using surface-enhanced Raman scattering. Individual Ag colloidal nanoparticles were screened from a large heterogeneous population for special size-dependent properties and were then used to amplify the speculation for special size-dependent properties and were then used to amplify the spectroscopic signatures of adsorbed mols. For single rhodamine 6G mols. adsorbed on the selected nanoparticles, the intrinsic Raman enhancement factors were ∼1014 to 1015, much larger than the ensemble-averaged values derived from conventional measurements. This enormous enhancement leads to vibrational Raman signals that are more intense and more stable than single-mol. fluorescence.
- 9Kneipp, K.; Wang, Y.; Kneipp, H.; Perelman, L. T.; Itzkan, I.; Dasari, R. R.; Feld, M. S. Single Molecule Detection Using Surface-Enhanced Raman Scattering (SERS). Phys. Rev. Lett. 1997, 78, 1667– 1670, DOI: 10.1103/PhysRevLett.78.1667Google Scholar9Single molecule detection using surface-enhanced Raman scattering (SERS)Kneipp, Katrin; Wang, Yang; Kneipp, Harald; Perelman, Lev T.; Itzkan, Irving; Dasari, Ramachandra R.; Feld, Michael S.Physical Review Letters (1997), 78 (9), 1667-1670CODEN: PRLTAO; ISSN:0031-9007. (American Physical Society)By exploiting the extremely large effective cross sections (10-17-10-16 cm2/mol.) available from surface-enhanced Raman scattering (SERS), the authors achieved the 1st observation of single mol. Raman scattering. Measured spectra of a single crystal violet mol. in aq. colloidal Ag soln. using one 2nd collection time and ∼2 × 105 W/cm2 nonresonant near-IR excitation show a clear fingerprint of its Raman features between 700 and 1700 cm-1. Spectra obsd. in a time sequence for an av. of 0.6 dye mol. in the probed vol. exhibited the expected Poisson distribution for actually measuring 0, 1, 2, or 3 mols.
- 10Qian, X.; Peng, X.-H.; Ansari, D. O.; Yin-Goen, Q.; Chen, G. Z.; Shin, D. M.; Yang, L.; Young, A. N.; Wang, M. D.; Nie, S. In vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tags. Nat. Biotechnol. 2008, 26, 83– 90, DOI: 10.1038/nbt1377Google Scholar10In vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tagsQian, Ximei; Peng, Xiang-Hong; Ansari, Dominic O.; Yin-Goen, Qiqin; Chen, Georgia Z.; Shin, Dong M.; Yang, Lily; Young, Andrew N.; Wang, May D.; Nie, ShumingNature Biotechnology (2008), 26 (1), 83-90CODEN: NABIF9; ISSN:1087-0156. (Nature Publishing Group)The authors describe biocompatible and nontoxic nanoparticles for in vivo tumor targeting and detection based on pegylated gold nanoparticles and surface-enhanced Raman scattering (SERS). Colloidal gold has been safely used to treat rheumatoid arthritis for 50 years, and has recently been found to amplify the efficiency of Raman scattering by 14-15 orders of magnitude. Here the authors show that large optical enhancements can be achieved under in vivo conditions for tumor detection in live animals. An important finding is that small-mol. Raman reporters such as org. dyes were not displaced but were stabilized by thiol-modified polyethylene glycols. These pegylated SERS nanoparticles were considerably brighter than semiconductor quantum dots with light emission in the near-IR window. When conjugated to tumor-targeting ligands such as single-chain variable fragment (ScFv) antibodies, the conjugated nanoparticles were able to target tumor biomarkers such as epidermal growth factor receptors on human cancer cells and in xenograft tumor models.
- 11Doctor, E. L.; McCord, B. Comparison of aggregating agents for the surface-enhanced Raman analysis of benzodiazepines. Analyst 2013, 138, 5926– 5932, DOI: 10.1039/c3an00669gGoogle ScholarThere is no corresponding record for this reference.
- 12Sahu, B. K.; Dwivedi, A.; Pal, K. K.; Pandian, R.; Dhara, S.; Das, A. Optimized Au NRs for efficient SERS and SERRS performances with molecular and longitudinal surface plasmon resonance. Appl. Surf. Sci. 2021, 537, 147615, DOI: 10.1016/j.apsusc.2020.147615Google Scholar12Optimized Au NRs for efficient SERS and SERRS performances with molecular and longitudinal surface plasmon resonanceSahu, Binaya Kumar; Dwivedi, Aradhana; Pal, Kuntal Kumar; Pandian, R.; Dhara, S.; Das, A.Applied Surface Science (2021), 537 (), 147615CODEN: ASUSEE; ISSN:0169-4332. (Elsevier B.V.)Chem. stable and biocompatible gold nanorods (Au NRs) are an excellent building block for plasmonic-based applications, including surface-enhanced Raman spectroscopy (SERS). However, the quest for controlling the aspect ratio (AR) for desirable application needs an in-depth understanding of the synthesis procedure. In this article, the seed-mediated growth of Au NRs with a controlled AR is reported. Influencing reagents, including the seed concn., are varied individually to unfurl the impact of them on AR. A subsequent optimized protocol is developed to achieve a fine-tuning in the longitudinal surface plasmonic resonance (LSPR) of Au NRs with a narrow distribution of NRs and minimal byproducts. The effect of resonance of LSPR peaks closely tallying both 785 and 532 nm with laser excitations are studied for SERS applications using rhodamine 6G (R6G) dye. Furthermore, the mol. resonance of R6G analyte is achieved successfully with a 532 nm excitation laser to accomplish as high of 10-12 M, thanks to the suitable ARs and the surface-enhanced resonance Raman scatterings (SERRS) phenomenon. The enhancement factor is calcd. to be 5 x 109, which allows Raman intensity mapping for a trace amt. of R6G, demonstrating the potential utility of Au NRs for applications.
- 13Valera, P. S.; Plou, J.; Garcia, I.; Astobiza, I.; Viera, C.; Aransay, A. M.; Martin, J. E.; Sasselli, I. R.; Carracedo, A.; Liz-Marzan, L. M. SERS analysis of cancer cell-secreted purines reveals a unique paracrine crosstalk in MTAP-deficient tumors. Proc. Natl. Acad. Sci. U. S. A. 2023, 120, e2311674120, DOI: 10.1073/pnas.2311674120Google ScholarThere is no corresponding record for this reference.
- 14Tian, L.; Su, M.; Yu, F.; Xu, Y.; Li, X.; Li, L.; Liu, H.; Tan, W. Liquid-state quantitative SERS analyzer on self-ordered metal liquid-like plasmonic arrays. Nat. Commun. 2018, 9, 3642, DOI: 10.1038/s41467-018-05920-zGoogle Scholar14Liquid-state quantitative SERS analyzer on self-ordered metal liquid-like plasmonic arraysTian Li; Su Mengke; Yu Fanfan; Xu Yue; Li Lei; Liu Honglin; Xu Yue; Liu Honglin; Tan Weihong; Li Xiaoyun; Tan WeihongNature communications (2018), 9 (1), 3642 ISSN:.Liquid interfacial plasmonic platform is emerging for new sensors, catalysis, and tunable optical devices, but also promises an alternative for practical applications of surface-enhanced Raman spectroscopy (SERS). Here we show that vigorous mixing of chloroform with citrate-capped gold nanorod sols triggers the rapid self-assembly of three-dimensional plasmonic arrays at the chloroform/water (O/W) interface and produces a self-healing metal liquid-like brilliant golden droplet. The O phase itself generates stable SERS fingerprints and is a good homogeneous internal standard for quantitative analysis. This platform presents reversible O/W encasing in a common cuvette determined just by surface wettability of the container. Both O-in-W and W-in-O platforms exhibit excellent SERS sensitivity and reproducibility for different analytes by the use of a portable Raman device. It paves the way toward a practical and quantitative liquid-state SERS analyzer, likened to a simple UV-Vis spectrometer, that is far superior to typical solid substrate-based or nanoparticle sol-based analysis.
- 15Ansar, S. M.; Ameer, F. S.; Hu, W.; Zou, S.; Pittman, C. U., Jr; Zhang, D. Removal of molecular adsorbates on gold nanoparticles using sodium borohydride in water. Nano Lett. 2013, 13, 1226– 9, DOI: 10.1021/nl304703wGoogle Scholar15Removal of Molecular Adsorbates on Gold Nanoparticles Using Sodium Borohydride in WaterAnsar, Siyam M.; Ameer, Fathima S.; Hu, Wenfang; Zou, Shengli; Pittman, Charles U.; Zhang, DongmaoNano Letters (2013), 13 (3), 1226-1229CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)The mechanism of sodium borohydride removal of organothiols from gold nanoparticles (AuNPs) was studied using an exptl. investigation and computational modeling. Organothiols and other AuNP surface adsorbates such as thiophene, adenine, rhodamine, small anions (Br- and I-), and a polymer (PVP, poly(N-vinylpyrrolidone)) can all be rapidly and completely removed from the AuNP surfaces. A computational study showed that hydride derived from sodium borohydride has a higher binding affinity to AuNPs than organothiols. Thus, it can displace organothiols and all the other adsorbates tested from AuNPs. Sodium borohydride may be used as a hazard-free, general-purpose detergent that should find utility in a variety of AuNP applications including catalysis, biosensing, surface enhanced Raman spectroscopy, and AuNP recycle and reuse.
- 16Bi, X.; Czajkowsky, D. M.; Shao, Z.; Ye, J. Digital colloid-enhanced Raman spectroscopy by single-molecule counting. Nature 2024, 628, 771– 775, DOI: 10.1038/s41586-024-07218-1Google ScholarThere is no corresponding record for this reference.
- 17Ye, Z.; Li, C.; Celentano, M.; Lindley, M.; O’Reilly, T.; Greer, A. J.; Huang, Y.; Hardacre, C.; Haigh, S. J.; Xu, Y.; Bell, S. E. J. Surfactant-free Synthesis of Spiky Hollow Ag–Au Nanostars with Chemically Exposed Surfaces for Enhanced Catalysis and Single-Particle SERS. JACS Au 2022, 2, 178– 187, DOI: 10.1021/jacsau.1c00462Google Scholar17Surfactant-free Synthesis of Spiky Hollow Ag-Au Nanostars with Chemically Exposed Surfaces for Enhanced Catalysis and Single-Particle SERSYe, Ziwei; Li, Chunchun; Celentano, Maurizio; Lindley, Matthew; O'Reilly, Tamsin; Greer, Adam J.; Huang, Yiming; Hardacre, Christopher; Haigh, Sarah J.; Xu, Yikai; Bell, Steven E. J.JACS Au (2022), 2 (1), 178-187CODEN: JAAUCR; ISSN:2691-3704. (American Chemical Society)Spiky/hollow metal nanoparticles have applications across a broad range of fields. However, the current bottom-up methods for producing spiky/hollow metal nanoparticles rely heavily on the use of strongly adsorbing surfactant mols., which is undesirable because these passivate the product particles' surfaces. Here we report a high-yield surfactant-free synthesis of spiky hollow Au-Ag nanostars (SHAANs). Each SHAAN is composed of >50 spikes attached to a hollow ca. 150 nm diam. cubic core, which makes SHAANs highly plasmonically and catalytically active. Moreover, the surfaces of SHAANs are chem. exposed, which gives them significantly enhanced functionality compared with their surfactant-capped counterparts, as demonstrated in surface-enhanced Raman spectroscopy (SERS) and catalysis. The chem. accessibility of the pristine SHAANs also allows the use of hydroxyethyl cellulose as a weakly bound stabilizing agent. This produces colloidal SHAANs that remain stable for >1 mo while retaining the functionalities of the pristine particles and allows even single-particle SERS to be realized.
- 18van Lierop, D.; Krpetić, Ž.; Guerrini, L.; Larmour, I. A.; Dougan, J. A.; Faulds, K.; Graham, D. Positively charged silver nanoparticles and their effect on surface-enhanced Raman scattering of dye-labelled oligonucleotides. Chem. Commun. 2012, 48, 8192– 8194, DOI: 10.1039/c2cc31731aGoogle Scholar18Positively charged silver nanoparticles and their effect on surface-enhanced Raman scattering of dye-labelled oligonucleotidesvan Lierop, Danny; Krpetic, Zeljka; Guerrini, Luca; Larmour, Iain A.; Dougan, Jennifer A.; Faulds, Karen; Graham, DuncanChemical Communications (Cambridge, United Kingdom) (2012), 48 (66), 8192-8194CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)Improved pos. charged nanoparticles are described to provide a simplified SERS substrate for DNA detection. Complete flocculation of the nanoparticles is prevented due to the controlled analyte induced aggregation. This provides a stable aggregation state which significantly extends the anal. window simplifying DNA detection by SERS.
- 19Stewart, A.; Bell, S. E. J. Modification of Ag nanoparticles with mixed thiols for improved SERS detection of poorly adsorbing target molecules: detection of MDMA. Chem. Commun. 2011, 47, 4523– 4525, DOI: 10.1039/c0cc05312kGoogle ScholarThere is no corresponding record for this reference.
- 20de Nijs, B.; Kamp, M.; Szabó, I.; Barrow, S. J.; Benz, F.; Wu, G.; Carnegie, C.; Chikkaraddy, R.; Wang, W.; Deacon, W. M.; Rosta, E.; Baumberg, J. J.; Scherman, O. A. Smart supramolecular sensing with cucurbit[n]urils: probing hydrogen bonding with SERS. Faraday Discuss. 2017, 205, 505– 515, DOI: 10.1039/C7FD00147AGoogle Scholar20Smart supramolecular sensing with cucurbit[n]urils: probing hydrogen bonding with SERSde Nijs, Bart; Kamp, Marlous; Szabo, Istvan; Barrow, Steven J.; Benz, Felix; Wu, Guanglu; Carnegie, Cloudy; Chikkaraddy, Rohit; Wang, Wenting; Deacon, William M.; Rosta, Edina; Baumberg, Jeremy J.; Scherman, Oren A.Faraday Discussions (2017), 205 (Surface Enhanced Raman Scattering--SERS), 505-515CODEN: FDISE6; ISSN:1359-6640. (Royal Society of Chemistry)Rigid gap nano-aggregates of Au nanoparticles formed using cucurbit[n]uril (CB[n]) mols. are used to investigate the competitive binding of ethanol and methanol in an aq. environment. We show it is possible to detect as little as 0.1% methanol in water and a ten times higher affinity to methanol over ethanol, making this a useful technol. for quality control in alc. prodn. We demonstrate strong interaction effects in the SERS peaks, which we demonstrate are likely from the hydrogen bonding of water complexes in the vicinity of the CB[n]s.
- 21Li, C.; Chen, Z.; Huang, Y.; Zhang, Y.; Li, X.; Ye, Z.; Xu, X.; Bell, S. E. J.; Xu, Y. Uncovering strong π-metal interactions on Ag and Au nanosurfaces under ambient conditions via in-situ surface-enhanced Raman spectroscopy. Chem. 2022, 8, 2514– 2528, DOI: 10.1016/j.chempr.2022.06.008Google Scholar21Uncovering strong π-metal interactions on Ag and Au nanosurfaces under ambient conditions via in-situ surface-enhanced Raman spectroscopyLi, Chunchun; Chen, Zheng; Huang, Yiming; Zhang, Yingrui; Li, Xinyuan; Ye, Ziwei; Xu, Xin; Bell, Steven E. J.; Xu, YikaiChem (2022), 8 (9), 2514-2528CODEN: CHEMVE; ISSN:2451-9294. (Cell Press)The interactions between arom. mols. and metal nanoparticles are ubiquitous in nanotechnol. Currently, π-metal interactions under ambient conditions are well appreciated for VIIIB but not for IB metals. Here, we demonstrate the direct probing of π-metal interactions under ambient conditions with mol. specificity using surface-enhanced Raman spectroscopy (SERS), which reveals that arom. hydrocarbons adsorb strongly from soln. onto the surfaces of Ag and Au nanoparticles, provided there is no surface oxidn. Theor. modeling shows that this adsorption is driven by dispersive π-metal interactions and that the arom. mols. co-adsorb alongside surface ligands that are present initially on the nanosurface. Finding direct evidence for this long-neglected interaction has significant implications for various applications. This is demonstrated with SERS sensing of an arom. drug mol. whose structure would typically suggest it to be weakly adsorbing, and indeed it is not detected on conventional Ag colloids due to surface oxidn., but it is found to adsorb strongly onto Au particles.
- 22Ye, Z.; Li, C.; Xu, Y.; Bell, S. E. J. Exploiting the chemical differences between Ag and Au colloids allows dramatically improved SERS detection of “non-adsorbing” molecules. Analyst 2019, 144, 448– 453, DOI: 10.1039/C8AN01927DGoogle Scholar22Exploiting the chemical differences between Ag and Au colloids allows dramatically improved SERS detection of "non-adsorbing" moleculesYe, Ziwei; Li, Chunchun; Xu, Yikai; Bell, Steven E. J.Analyst (Cambridge, United Kingdom) (2019), 144 (2), 448-453CODEN: ANALAO; ISSN:0003-2654. (Royal Society of Chemistry)In colloidal SERS only analytes that can spontaneously adsorb onto nanoparticles are detected. Therefore, considerable effort has been placed on modifying the surface properties of colloidal particles, particularly Ag particles, to promote the absorption of "difficult" analytes which do not spontaneously adsorb to as-prepd. nanoparticles. In contrast, much less attention has been paid to the role which the identity of the underlying metal plays in the absorption since it is widely believed that the chem. properties of Ag and Au are very similar. This leads to the assumption that mols. which do not adsorb to Ag, such as hydrocarbons, will also not adsorb to aggregated Au colloids for SERS measurements. Here, we challenge this common perception by showing that SERS detection of "difficult" arom. targets such as naphthalene, trinitrotoluene and 3,4-methylenedioxymethamphetamine which cannot be achieved even at >10-3 M concns. with bare aggregated Ag colloids is possible at ≥10-8 M with unmodified aggregated Au colloids. For naphthalene and 3,4-methylenedioxymethamphetamine the detection limit obtained in this work with bare citrate-capped Au particles exceeds the previous best limit of detection obtained with surface-modified nanoparticles by an order of magnitude.
- 23Bell, S. E. J.; Sirimuthu, N. M. S. Surface-Enhanced Raman Spectroscopy (SERS) for Sub-Micromolar Detection of DNA/RNA Mononucleotides. J. Am. Chem. Soc. 2006, 128, 15580– 15581, DOI: 10.1021/ja066263wGoogle Scholar23Surface-Enhanced Raman Spectroscopy (SERS) for Sub-Micromolar Detection of DNA/RNA MononucleotidesBell, Steven E. J.; Sirimuthu, Narayana M. S.Journal of the American Chemical Society (2006), 128 (49), 15580-15581CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Surface-enhanced Raman (SER) spectra of all the DNA/RNA mononucleotides have been obtained with high sensitivity using citrate-reduced silver colloids aggregated with MgSO4, rather than the more usual halide ions, which were found to prevent enhancement of these compds. The SERS spectra of adenine, guanine, thymine, cytosine, and uracil were recorded along with their corresponding nucleosides and 5'-deoxynucleotides. For the cytosine series, all three spectra had similar relative band intensities but the spectra of adenine were different from those of adenosine and dAMP, probably due to differences in orientation on the surface. No enhanced bands from the phosphate or sugar groups were obsd. There were general similarities between the SERS spectra of the purine mononucleotides and the pyrimidine mononucleotides, but the spectra were sufficiently different to allow each of them to be distinguished. This method can therefore be used for high sensitivity, label-free identification of mononucleotides.
- 24Xie, L.; Lu, J.; Liu, T.; Chen, G.; Liu, G.; Ren, B.; Tian, Z. Key Role of Direct Adsorption on SERS Sensitivity: Synergistic Effect among Target, Aggregating Agent, and Surface with Au or Ag Colloid as Surface-Enhanced Raman Spectroscopy Substrate. J. Phys. Chem. Lett. 2020, 11, 1022– 1029, DOI: 10.1021/acs.jpclett.9b03724Google Scholar24Key Role of Direct Adsorption on SERS Sensitivity: Synergistic Effect among Target, Aggregating Agent, and Surface with Au or Ag Colloid as Surface-Enhanced Raman Spectroscopy SubstrateXie, Lifang; Lu, Jianglong; Liu, Tao; Chen, Ganyu; Liu, Guokun; Ren, Bin; Tian, ZhongqunJournal of Physical Chemistry Letters (2020), 11 (3), 1022-1029CODEN: JPCLCD; ISSN:1948-7185. (American Chemical Society)It is widely accepted that the sensitivity of surface-enhanced Raman spectroscopy (SERS) is mainly manipulated by the electromagnetic enhancement mechanism (EM). Herein, the direct adsorption of the target on the SERS active surface is vital as well, through the systematic study of the SERS behavior of 3 pos. charged mols. on neg. charged Au or Ag nanoparticles. Facilitated by the synergistic effect among the mol., the surface, and the specific adsorbed halide ions (Cl-, Br-, and I-), high SERS sensitivity for trace target was realized, which was mainly from the directly adsorbed mols. Noteworthy, little contribution from the nondirectly adsorbed mols. was discernible, although the EM enhancement was at the same level for these 2 surface species dwelling within a distance significantly <1 nm from the surface. Further, the related strategy for trace detection sheds light on how to realize sensitive SERS detection of new targets.
- 25Zhou, Z.; Lu, J.; Wang, J.; Zou, Y.; Liu, T.; Zhang, Y.; Liu, G.; Tian, Z. Trace detection of polycyclic aromatic hydrocarbons in environmental waters by SERS. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 2020, 234, 118250, DOI: 10.1016/j.saa.2020.118250Google ScholarThere is no corresponding record for this reference.
- 26Simpson, J.; Craig, D.; Faulds, K.; Graham, D. Mixed-monolayer glyconanoparticles for the detection of cholera toxin by surface enhanced Raman spectroscopy. Nanoscale Horizons 2016, 1, 60– 63, DOI: 10.1039/C5NH00036JGoogle ScholarThere is no corresponding record for this reference.
- 27Gao, J.; Huang, X.; Liu, H.; Zan, F.; Ren, J. Colloidal Stability of Gold Nanoparticles Modified with Thiol Compounds: Bioconjugation and Application in Cancer Cell Imaging. Langmuir 2012, 28, 4464– 4471, DOI: 10.1021/la204289kGoogle Scholar27Colloidal Stability of Gold Nanoparticles Modified with Thiol Compounds: Bioconjugation and Application in Cancer Cell ImagingGao, Jie; Huang, Xiangyi; Liu, Heng; Zan, Feng; Ren, JicunLangmuir (2012), 28 (9), 4464-4471CODEN: LANGD5; ISSN:0743-7463. (American Chemical Society)Gold nanoparticles (GNPs) are attractive alternative optical probes and good biocompatible materials due to their special phys. and chem. properties. However, GNPs have a tendency to aggregate particularly in the presence of high salts and certain biol. mols. such as nucleic acids and proteins. How to improve the stability of GNPs and their bioconjugates in aq. soln. is a crit. issue in bioapplications. In this study, we first synthesized 17 nm GNPs in aq. soln. and then modified them with six thiol compds., including glutathione, mercaptopropionic acid (MPA), cysteine, cystamine, dihydrolipoic acid, and thiol-ending polyethylene glycol (PEG-SH), via a Au-S bond. We systematically investigated the effects of the thiol ligands, buffer pH, and salt concns. of the solns. on the colloidal stability of GNPs using UV-vis absorption spectroscopy. We found that GNPs modified with PEG-SH were the most stable in aq. soln. compared to other thiol compds. On the basis of the above results, we developed a simple and efficient approach for modification of GNPs using a mixt. of PEG-SH and MPA as ligands. These biligand-modified GNPs were facilely conjugated to antibody using 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide and N-hydroxysulfosuccinimide as linkage reagents. We conjugated GNPs to epidermal growth factor receptor antibodies and successfully used the antibody-GNP conjugates as targeting probes for imaging of cancer cells using the illumination of a dark field. Compared to current methods for modification and conjugation of GNPs, our method described here is simple, has a low cost, and has potential applications in bioassays and cancer diagnostics and studies.
- 28Gu, Y.; Wu, S.; Luo, Z.; Lin, L. L.; Ye, J. Oppositely-charged silver nanoparticles enable selective SERS molecular enhancement through electrostatic interactions. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 2024, 322, 124852, DOI: 10.1016/j.saa.2024.124852Google ScholarThere is no corresponding record for this reference.
- 29Milligan, K.; Shand, N. C.; Graham, D.; Faulds, K. Detection of Multiple Nitroaromatic Explosives via Formation of a Janowsky Complex and SERS. Anal. Chem. 2020, 92, 3253– 3261, DOI: 10.1021/acs.analchem.9b05062Google Scholar29Detection of Multiple Nitroaromatic Explosives via Formation of a Janowsky Complex and SERSMilligan, Kirsty; Shand, Neil C.; Graham, Duncan; Faulds, KarenAnalytical Chemistry (Washington, DC, United States) (2020), 92 (4), 3253-3261CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Military-grade explosives such as 2,4,6-trinitroluene (TNT) are still a major worldwide concern in terms of terror threat and environmental impact. The most common methods currently employed for the detection of explosives involve colorimetric tests, which are known to be rapid and portable; however, they often display false positives and lack sensitivity. Other methods used include ion mobility mass spectrometry, gas chromatog.-mass spectrometry (GC-MS), and liq. chromatog.-mass spectrometry (LC-MS), which despite producing more reliable results often require large, expensive instrumentation and specially trained staff. Here we demonstrate an alternative approach that utilizes the formation of a colored Janowsky complex with nitroarom. explosives through reaction of the enolate ion of 3-mercapto-2-butanone. The colored complex is formed rapidly and can then be detected sensitively using surface-enhanced Raman scattering (SERS). We demonstrate that SERS can be used as a quick, sensitive, and selective technique for the detection of 2,4,6-trinitrotoluene (TNT), hexanitrostillbene (HNS), and 2,4,6-trinitrophenylmethylnitramine (tetryl) with a detection limit of 6.81 ng mL-1 achieved for TNT, 17.2 ng mL-1 for tetryl, and 135.1 ng mL-1 for HNS. This method of detection also requires minimal sample prepn., can be done in a soln.-based format, and utilizes the same precursor reagents for complex formation with each of the explosives which can then be identified due to the specificity of the unique SERS response obtained. We demonstrate the ability to simultaneously identify three explosive compds. within a total anal. time of 10 min. This method of detection shows promise for the development of rapid and portable SERS-based assays which can be utilized in the field in order to achieve reliable and quant. detection.
- 30Saha, K.; Agasti, S. S.; Kim, C.; Li, X.; Rotello, V. M. Gold Nanoparticles in Chemical and Biological Sensing. Chem. Rev. 2012, 112, 2739– 2779, DOI: 10.1021/cr2001178Google Scholar30Gold nanoparticles in chemical and biological sensingSaha, Krishnendu; Agasti, Sarit S.; Kim, Chaekyu; Li, Xiaoning; Rotello, Vincent M.Chemical Reviews (Washington, DC, United States) (2012), 112 (5), 2739-2779CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review. Topics include synthesis ans surface functionalization; phys. properties; colorimetric and fluorimetric sensing; elec. al and electrochem. sensing; SERS; gold nanoparticles in quartz crystal microbalance-based sensing; application of gold nanoparticles in bio-barcode assays.
- 31Kasera, S.; Biedermann, F.; Baumberg, J. J.; Scherman, O. A.; Mahajan, S. Quantitative SERS Using the Sequestration of Small Molecules Inside Precise Plasmonic Nanoconstructs. Nano Lett. 2012, 12, 5924– 5928, DOI: 10.1021/nl303345zGoogle Scholar31Quantitative SERS Using the Sequestration of Small Molecules Inside Precise Plasmonic NanoconstructsKasera, Setu; Biedermann, Frank; Baumberg, Jeremy J.; Scherman, Oren A.; Mahajan, SumeetNano Letters (2012), 12 (11), 5924-5928CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)The authors show how the macrocyclic host, cucurbit[8]uril (CB[8]), creates precise subnanometer junctions between gold nanoparticles while its cavity simultaneously traps small mols.; this enables their reproducible surface-enhanced Raman spectroscopy (SERS) detection. Explicit shifts in the SERS frequencies of CB[8] on complexation with guest mols. provides a direct strategy for abs. quantification of a range of mols. down to 10-11 M levels. This provides a new anal. paradigm for quant. SERS of small mols.
- 32Stewart, A.; Murray, S.; Bell, S. E. J. Simple preparation of positively charged silver nanoparticles for detection of anions by surface-enhanced Raman spectroscopy. Analyst 2015, 140, 2988– 2994, DOI: 10.1039/C4AN02305FGoogle Scholar32Simple preparation of positively charged silver nanoparticles for detection of anions by surface-enhanced Raman spectroscopyStewart, A.; Murray, S.; Bell, S. E. J.Analyst (Cambridge, United Kingdom) (2015), 140 (9), 2988-2994CODEN: ANALAO; ISSN:0003-2654. (Royal Society of Chemistry)Modification of citrate and hydroxylamine reduced Ag colloids with thiocholine bromide, a thiol functionalized quaternary ammonium salt, creates particles where the zeta potential is switched from the normal values of ∼-50 mV to approx. + 50 mV. These colloids are stable but can be aggregated with metal salts in much the same way as the parent colloids. They are excellent SERS substrates for detection of anionic targets since their pos. zeta potentials promote adsorption of neg. charged ions. This is important because the vast majority of published SERS studies involve cationic or neutral targets. Also, the fact that the modifier is a quaternary ammonium ion means that the neg. surface charge is maintained even at alk. pH. The modified colloids can be used to detect compds. which cannot be detected using conventional neg.-charged citrate or hydroxylamine reduced metal nanoparticles, for example the detection limit was 5.0 × 10-5 M for perchlorate and <8.7 × 10-7 M for tetraphenylporphine tetrasulfonic acid (TPPS). More importantly, picric acid (an explosive) and diclofenac (a nonsteroidal antiinflammatory) could also be analyzed quant. at low concns., 2.5 × 10-5 M and 1.9 × 10-5 M, resp. The correct choice of aggregating agent is important for achieving high sensitivity since the anion in the aggregating salt may compete with anionic targets for surface binding sites. Finally, since the modification procedure simply involves reaction of nanoparticles with a small alkyl thiol deriv., it can easily be adapted to other particle morphologies or metals.
- 33Guan, P.-C.; Zhang, H.; Li, Z.-Y.; Xu, S.-S.; Sun, M.; Tian, X.-M.; Ma, Z.; Lin, J.-S.; Gu, M.-M.; Wen, H.; Zhang, F.-L.; Zhang, Y.-J.; Yu, G.-J.; Yang, C.; Wang, Z.-X.; Song, Y.; Li, J.-F. Rapid Point-of-Care Assay by SERS Detection of SARS-CoV-2 Virus and Its Variants. Anal. Chem. 2022, 94, 17795– 17802, DOI: 10.1021/acs.analchem.2c03437Google Scholar33Rapid Point-of-Care Assay by SERS Detection of SARS-CoV-2 Virus and Its VariantsGuan, Peng-Cheng; Zhang, Hong; Li, Zhi-Yong; Xu, Shan-Shan; Sun, Miao; Tian, Xian-Min; Ma, Zhan; Lin, Jia-Sheng; Gu, Man-Man; Wen, Huan; Zhang, Fan-Li; Zhang, Yue-Jiao; Yu, Guang-Jun; Yang, Chaoyong; Wang, Zhan-Xiang; Song, Yanling; Li, Jian-FengAnalytical Chemistry (Washington, DC, United States) (2022), 94 (51), 17795-17802CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Addressing the spread of coronavirus disease 2019 (COVID-19) has highlighted the need for rapid, accurate, and low-cost diagnostic methods that detect specific antigens for SARS-CoV-2 infection. Tests for COVID-19 are based on reverse transcription PCR (RT-PCR), which requires lab. services and is time-consuming. Here, by targeting the SARS-CoV-2 spike protein, we present a point-of-care SERS detection platform that specifically detects SARS-CoV-2 antigen in one step by captureing substrates and detection probes based on aptamer-specific recognition. Using the pseudovirus, without any pretreatment, the SARS-CoV-2 virus and its variants were detected by a handheld Raman spectrometer within 5 min. The limit of detection (LoD) for the pseudovirus was 124 TU μL-1 (18 fM spike protein), with a linear range of 250-10,000 TU μL-1. Moreover, this assay can specifically recognize the SARS-CoV-2 antigen without cross reacting with specific antigens of other coronaviruses or influenza A. Therefore, the platform has great potential for application in rapid point-of-care diagnostic assays for SARS-CoV-2.
- 34Nguyen, M. T. T.; Dang, L. T.; Van Pham, H. Gold nanorods coated by molecularly imprinted polymer for sensitive and specific SERS detection of dyes. Colloid Polym. Sci. 2023, 301, 577– 586, DOI: 10.1007/s00396-023-05097-yGoogle Scholar34Gold nanorods coated by molecularly imprinted polymer for sensitive and specific SERS detection of dyesNguyen, Mai Tuyet Thi; Dang, Lan Thi; Van Pham, HaiColloid and Polymer Science (2023), 301 (6), 577-586CODEN: CPMSB6; ISSN:0303-402X. (Springer)Although surface-enhanced Raman scattering (SERS) is an advanced anal. technique, the challenge of low specificity in real sample anal. remains. In this study, we synthesized a hybrid structure based on gold nanorods (AuNRs) coated with a molecularly imprinted polymer (MIP) as a SERS substrate. While the AuNRs strongly enhance the Raman signal of the analyte, the MIP layer allows specific trapping of analyte mols. close to the gold surface. A very thin film of polydopamine with exclusive cavities of rhodamine B enabled ultrasensitive detection of rhodamine B with a 120-fold increase compared to non-imprinted sample. The selectivity of our AuNR@MIP substrate for the detection of rhodamine B in a mixt. of different dyes was also clearly improved. Fortunately, the AuNR@MIP substrate exhibited attractive accuracy and sensitivity toward rhodamine B in spiked orange juice samples. This report demonstrates a promising hybrid structure to improve SERS-based sensing of real samples.
- 35Ding, Q.; Wang, J.; Chen, X.; Liu, H.; Li, Q.; Wang, Y.; Yang, S. Quantitative and Sensitive SERS Platform with Analyte Enrichment and Filtration Function. Nano Lett. 2020, 20, 7304– 7312, DOI: 10.1021/acs.nanolett.0c02683Google Scholar35Quantitative and Sensitive SERS Platform with Analyte Enrichment and Filtration FunctionDing, Qianqian; Wang, Jing; Chen, Xueyan; Liu, Hong; Li, Quanjiang; Wang, Yanling; Yang, ShikuanNano Letters (2020), 20 (10), 7304-7312CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)Surface-enhanced Raman scattering (SERS) technique with naturally born analyte identification capability can achieve ultrahigh sensitivity. However, the sensitivity and quantification capability of SERS are assumed to be mutually exclusive. Here, the authors prohibit the formation of the ultrasensitive SERS sites to achieve a high quantification capability through sepg. the gold (Au) nanorods from approaching each other with thick metal org. framework (MOF) shells. The sensitivity decrease caused by the absence of the ultrasensitive SERS sites is compensated by the analyte enrichment function of a slippery surface. The porous MOF shell around the Au nanorod only allows analytes smaller than the pore size to approach the Au nanorods and contribute to the SERS spectrum within the complex sample, greatly enhancing the analyte identification capability. Overall, the authors demonstrated an integrated SERS platform with analyte enrichment and analyte filtration function, realizing sensitive, quant., and size selective analyte identification in complex environments.
- 36Zhang, L.; Liu, F.; Zou, Y.; Hu, X.; Huang, S.; Xu, Y.; Zhang, L.; Dong, Q.; Liu, Z.; Chen, L.; Chen, Z.; Tan, W. Surfactant-Free Interface Suspended Gold Graphitic Surface-Enhanced Raman Spectroscopy Substrate for Simultaneous Multiphase Analysis. Anal. Chem. 2018, 90, 11183– 11187, DOI: 10.1021/acs.analchem.8b03040Google Scholar36Surfactant-Free Interface Suspended Gold Graphitic Surface-Enhanced Raman Spectroscopy Substrate for Simultaneous Multiphase AnalysisZhang, Liang; Liu, Fang; Zou, Yuxiu; Hu, Xiaoxiao; Huang, Siqi; Xu, Yiting; Zhang, Lufeng; Dong, Qian; Liu, Zhangkun; Chen, Long; Chen, Zhuo; Tan, WeihongAnalytical Chemistry (Washington, DC, United States) (2018), 90 (19), 11183-11187CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Simultaneous multiphase detection of multiplex analytes is important, albeit challenging, esp. in pharmaceuticals anal. since drugs with lipid and water soly. were often administered together for synergistic therapy. Surface-enhanced Raman spectroscopy (SERS) is a label-free and sensitive tool for multiplex analytes detection at multiphase interfaces. However, the requirements of inducers or surfactant surface modification of the SERS substrate have restricted extensive applications. Herein, the authors developed a graphene-isolated-Au-nanocrystal based multiphase anal. system. Unexpectedly, the gold graphitic SERS substrate can simply suspend at the interface of the different phase without the involvement of any surfactant. Therefore, the proximity of substrate with analyte mols. remains unaffected. Such suspended substrate not only ensures sensitive SERS detection but also enables the enrichment of analytes from the different phase simultaneously without interference. Moreover, the graphitic shell of the SERS substrate has a unique vibration band located in the Raman biol. silence region which is utilized as the internal std. and improves the SERS quantification accuracy. Efficient ex vivo multiphase enrichment and detection of mimic lipid- and water-sol. drugs injected into mice were demonstrated with such gold graphitic substrate, showing the potential of this simultaneous multiplex pharmacokinetic anal.
- 37Kwon, S.; Oh, M. J.; Lee, S.; Lee, G.; Jung, I.; Oh, M.; Park, S. Au Octahedral Nanosponges: 3D Plasmonic Nanolenses for Near-Field Focusing. J. Am. Chem. Soc. 2023, 145, 27397– 27406, DOI: 10.1021/jacs.3c08315Google ScholarThere is no corresponding record for this reference.
- 38Oh, M. J.; Kwon, S.; Lee, S.; Jung, I.; Park, S. Octahedron in a Cubic Nanoframe: Strong Near-Field Focusing and Surface-Enhanced Raman Scattering. ACS Nano 2024, 18, 7656– 7665, DOI: 10.1021/acsnano.4c00734Google ScholarThere is no corresponding record for this reference.
- 39Zhao, L.; Wang, Y.; Jin, S.; An, N.; Yan, M.; Zhang, X.; Hong, Z.; Yang, S. Rational Electrochemical Design of Hierarchical Microarchitectures for SERS Sensing Applications. Nat. Synth. 2024, 3, 867– 877, DOI: 10.1038/s44160-024-00553-1Google ScholarThere is no corresponding record for this reference.
- 40Xiong, M.; Jin, X.; Ye, J. Strong plasmon coupling in self-assembled superparamagnetic nanoshell chains. Nanoscale 2016, 8, 4991– 4999, DOI: 10.1039/C5NR09101BGoogle Scholar40Strong plasmon coupling in self-assembled superparamagnetic nanoshell chainsXiong, Min; Jin, Xiulong; Ye, JianNanoscale (2016), 8 (9), 4991-4999CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)Construction of ordered patterns of plasmonic nanoparticles is greatly important for nanophotonics relevant applications. We have reported a facile and low-cost magnetic field induced self-assembly approach to construct plasmonic superparamagnetic nanoshell (SN) chains up to several hundred micrometers in a few seconds in a large area without templates or other assistance processes. Exptl. and theor. investigations of the near- and far-field optical properties indicate that the super- and sub-radiant modes of the SN chains continuously red shift with the increase of SN no. and the Fano resonance emerges in the infinite double- and triple-line SN chains. Strong plasmon coupling effects in the SN chains result in great elec. field enhancements at visible and IR wavelengths, which indicates that these chain structures potentially can be used as a common substrate for both surface enhanced Raman scattering (SERS) and surface-enhanced IR absorption (SEIRA) application. This fabrication method also offers a general strategy alternative to top-down processing that enables the construction of nanostructures for metamaterials, electromagnetic energy transport, and optical waveguide.
- 41Ye, J.; Wen, F.; Sobhani, H.; Lassiter, J. B.; Van Dorpe, P.; Nordlander, P.; Halas, N. J. Plasmonic nanoclusters: near field properties of the Fano resonance interrogated with SERS. Nano Lett. 2012, 12, 1660– 7, DOI: 10.1021/nl3000453Google Scholar41Plasmonic Nanoclusters: Near Field Properties of the Fano Resonance Interrogated with SERSYe, Jian; Wen, Fangfang; Sobhani, Heidar; Lassiter, J. Britt; Dorpe, Pol Van; Nordlander, Peter; Halas, Naomi J.Nano Letters (2012), 12 (3), 1660-1667CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)While the far field properties of Fano resonances are well-known, clusters of plasmonic nanoparticles also possess Fano resonances with unique and spatially complex near field properties. Here we examine the near field properties of individual Fano resonant plasmonic clusters using surface-enhanced Raman scattering (SERS) both from mols. distributed randomly on the structure and from dielec. nanoparticles deposited at specific locations within the cluster. Cluster size, geometry, and interparticle spacing all modify the near field properties of the Fano resonance. For mols., the spatially dependent SERS response obtained from near field calcns. correlates well with the relative SERS intensities obsd. for individual clusters and for specific Stokes modes of a para-mercaptoaniline adsorbate. In all cases, the largest SERS enhancement is found when both the excitation and the Stokes shifted wavelengths overlap the Fano resonances. In contrast, for SERS from carbon nanoparticles we find that the dielec. screening introduced by the nanoparticle can drastically redistribute the field enhancement assocd. with the Fano resonance and lead to a significantly modified SERS response compared to what would be anticipated from the bare nanocluster.
- 42Zhao, Y.; Shi, L.; Tian, Y.; Zhang, L. Self-assembly at Liquid-Liquid Interface: A New SERS Substrate for Analytical Sensing†. Chin. J. Chem. 2023, 41, 569– 580, DOI: 10.1002/cjoc.202200508Google ScholarThere is no corresponding record for this reference.
- 43Yogev, D.; Efrima, S. Novel silver metal liquidlike films. J. Phys. Chem. 1988, 92, 5754– 5760, DOI: 10.1021/j100331a041Google ScholarThere is no corresponding record for this reference.
- 44Gordon, K. C.; McGarvey, J. J.; Taylor, K. P. Enhanced Raman scattering from liquid metal films formed from silver sols. J. Phys. Chem. 1989, 93, 6814– 6817, DOI: 10.1021/j100355a046Google ScholarThere is no corresponding record for this reference.
- 45Booth, S. G.; Dryfe, R. A. W. Assembly of Nanoscale Objects at the Liquid/Liquid Interface. J. Phys. Chem. C 2015, 119, 23295– 23309, DOI: 10.1021/acs.jpcc.5b07733Google Scholar45Assembly of Nanoscale Objects at the Liquid/Liquid InterfaceBooth, Samuel G.; Dryfe, Robert A. W.Journal of Physical Chemistry C (2015), 119 (41), 23295-23309CODEN: JPCCCK; ISSN:1932-7447. (American Chemical Society)A review. Self-assembly of various materials, such as metallic nanoparticles, Janus particles, and carbon nanomaterials, at liq.-liq. interface is discussed. Strategies to induce particle assembly include manipulation of surface chem., surface charge, and potential control. Liq./liq. assembly can be exploited to synthesize materials in situ and template preformed structures. The difficulties encountered when attempting to fully understand the structure of assemblies present at the liq./liq. interface and the development of exptl. techniques to elucidate information about the structure, stability, chem. compn., and reactivity of interfacial assemblies, are discussed.
- 46Ye, Z.; Li, C.; Chen, Q.; Xu, Y.; Bell, S. E. J. Self-assembly of colloidal nanoparticles into 2D arrays at water–oil interfaces: rational construction of stable SERS substrates with accessible enhancing surfaces and tailored plasmonic response. Nanoscale 2021, 13, 5937– 5953, DOI: 10.1039/D0NR08803JGoogle Scholar46Self-assembly of colloidal nanoparticles into 2D arrays at water-oil interfaces: rational construction of stable SERS substrates with accessible enhancing surfaces and tailored plasmonic responseYe, Ziwei; Li, Chunchun; Chen, Qinglu; Xu, Yikai; Bell, Steven E. J.Nanoscale (2021), 13 (12), 5937-5953CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)A review. Self-assembly at water-oil interfaces has been shown to be a cheap, convenient and efficient route to obtain densely packed layers of plasmonic nanoparticles which have small interparticle distances. This creates highly plasmonically active materials that can be used to give strong SERS enhancement and whose structure means that they are well suited to creating the highly stable, reproducible and uniform substrates that are needed to allow routine and accurate quant. SERS measurements. A variety of methods have been developed to induce nanoparticle self-assembly at water-oil interfaces, fine tune the surface chem. and adjust the position of the nanoparticles at the interface but only some of these are compatible with eventual use in SERS, where it is important that target mols. can access the active surface unimpeded. Similarly, it is useful to transform liq. plasmonic arrays into easy-to-handle free-standing solid films but these can only be used as solid SERS substrates if the process leaves the surface nanoparticles exposed. Here, we review the progress made in these research areas and discuss how these developments may lead towards achieving rational construction of tailored SERS substrates for sensitive and quant. SERS anal.
- 47Yang, N.; You, T.; Gao, Y.; Lu, S.; Yin, P. One-Step Preparation Method of Flexible Metafilms on the Water–Oil Interface: Self-Assembly Surface Plasmon Structures for Surface-Enhanced Raman Scattering Detection. Langmuir 2019, 35, 4626– 4633, DOI: 10.1021/acs.langmuir.8b04271Google Scholar47One-Step Preparation Method of Flexible Metafilms on the Water-Oil Interface: Self-Assembly Surface Plasmon Structures for Surface-Enhanced Raman Scattering DetectionYang, Nan; You, Tingting; Gao, Yukun; Lu, Sichen; Yin, PenggangLangmuir (2019), 35 (13), 4626-4633CODEN: LANGD5; ISSN:0743-7463. (American Chemical Society)The present study demonstrated a one-step method for the first time to fabricate self-assembled gold nanoparticle (AuNP) metafilms at the water-toluene interface by adding polystyrene-polyisoprene-polystyrene as the support layer. The thiolated polyethylene glycol and ethanol were used to tune the surface charge d. on the AuNPs, constructing a balanced situation at the water-toluene interface. The flexible (AuNP) metafilm can be easily obtained after evapn. of the toluene phase and further used as a surface-enhanced Raman scattering (SERS) substrate for trace thiram detection. The SERS sensitivity was tested using std. Raman probes such as crystal violet and malachite green, both with the detect concn. reaching 1 × 10-11 M. Moreover, the excellent reproducibility and elastic properties make the metafilm promising in practical detection. Hence, the trace thiram detection on an orange pericarp was inspected with the detection limit of 0.5 ppm (1 × 10-6 M) as well as a favorable linearity relation with a correlation coeff. of 0.979, exactly matching the realistic application requirements.
- 48Lee, Y. H.; Lee, H. K.; Ho, J. Y. C.; Yang, Y.; Ling, X. Y. Assembling substrate-less plasmonic metacrystals at the oil/water interface for multiplex ultratrace analyte detection. Analyst 2016, 141, 5107– 5112, DOI: 10.1039/C6AN01239FGoogle Scholar48Assembling substrate-less plasmonic metacrystals at the oil/water interface for multiplex ultratrace analyte detectionLee, Yih Hong; Lee, Hiang Kwee; Ho, Jonathan Yong Chew; Yang, Yijie; Ling, Xing YiAnalyst (Cambridge, United Kingdom) (2016), 141 (17), 5107-5112CODEN: ANALAO; ISSN:0003-2654. (Royal Society of Chemistry)Current substrate-less SERS platforms are limited to uncontrolled aggregation of plasmonic nanoparticles or quasi-cryst. arrays of spherical nanoparticles, with no study on how the lattice structures formed by nanoparticle self-assembly affect their detection capabilities. Here, we organize Ag octahedral building blocks into two large-area plasmonic metacrystals at the oil/water interface, and investigate their in situ SERS sensing capabilities. Amphiphilic octahedra assemble into a hcp. metacrystal, while hydrophobic octahedra assemble into an open square metacrystal. The lower packing d. square metacrystal gives rise to much stronger SERS enhancement than the denser packing hexagonal metacrystal, arising from the larger areas of plasmonic hotspots within the square metacrystal at the excitation wavelength. We further demonstrate the ability of the square metacrystal to achieve quant. ultratrace detection of analytes from both the aq. and org. phases. Detection limits are at the nano-molar levels, with anal. enhancement factors reaching 108. In addn., multiplex detection across both phases can be achieved in situ without any loss of signal quantitation.
- 49Zhang, Y.; Ye, Z.; Li, C.; Chen, Q.; Aljuhani, W.; Huang, Y.; Xu, X.; Wu, C.; Bell, S. E. J.; Xu, Y. General approach to surface-accessible plasmonic Pickering emulsions for SERS sensing and interfacial catalysis. Nat. Commun. 2023, 14, 1392, DOI: 10.1038/s41467-023-37001-1Google Scholar49General approach to surface-accessible plasmonic Pickering emulsions for SERS sensing and interfacial catalysisZhang, Yingrui; Ye, Ziwei; Li, Chunchun; Chen, Qinglu; Aljuhani, Wafaa; Huang, Yiming; Xu, Xin; Wu, Chunfei; Bell, Steven E. J.; Xu, YikaiNature Communications (2023), 14 (1), 1392CODEN: NCAOBW; ISSN:2041-1723. (Nature Portfolio)Pickering emulsions represent an important class of functional materials with potential applications in sustainability and healthcare. Currently, the synthesis of Pickering emulsions relies heavily on the use of strongly adsorbing mol. modifiers to tune the surface chem. of the nanoparticle constituents. This approach is inconvenient and potentially a dead-end for many applications since the adsorbed modifiers prevent interactions between the functional nanosurface and its surroundings. Here, we demonstrate a general modifier-free approach to construct Pickering emulsions by using a combination of stabilizer particles, which stabilize the emulsion droplet, and a second population of unmodified functional particles that sit alongside the stabilizers at the interface. Freeing Pickering emulsions from chem. modifiers unlocks their potential across a range of applications including plasmonic sensing and interfacial catalysis that have previously been challenging to achieve. More broadly, this strategy provides an approach to the development of surface-accessible nanomaterials with enhanced and/or addnl. properties from a wide range of nano-building blocks including org. nanocrystals, carbonaceous materials, metals and oxides.
- 50Tian, H.; Li, H.; Fang, Y. Binary Thiol-Capped Gold Nanoparticle Monolayer Films for Quantitative Surface-Enhanced Raman Scattering Analysis. ACS Appl. Mater. & Interfaces 2019, 11, 16207– 16213, DOI: 10.1021/acsami.9b02069Google ScholarThere is no corresponding record for this reference.
- 51Wang, X.; Liang, Z.; Chi, X.; Zhao, M.; Shi, X.; Ma, Y. The construction and destruction of gold nanoparticle assembly at liquid-liquid interface for Cd2+ sensing. Anal. Chim. Acta 2022, 1234, 340520, DOI: 10.1016/j.aca.2022.340520Google ScholarThere is no corresponding record for this reference.
- 52Si, S.; Liang, W.; Sun, Y.; Huang, J.; Ma, W.; Liang, Z.; Bao, Q.; Jiang, L. Facile Fabrication of High-Density Sub-1-nm Gaps from Au Nanoparticle Monolayers as Reproducible SERS Substrates. Adv. Funct. Mater. 2016, 26, 8137– 8145, DOI: 10.1002/adfm.201602337Google Scholar52Facile Fabrication of High-Density Sub-1-nm Gaps from Au Nanoparticle Monolayers as Reproducible SERS SubstratesSi, Shaorong; Liang, Wenkai; Sun, Yinghui; Huang, Jing; Ma, Weiliang; Liang, Zhiqiang; Bao, Qiaoliang; Jiang, LinAdvanced Functional Materials (2016), 26 (44), 8137-8145CODEN: AFMDC6; ISSN:1616-301X. (Wiley-VCH Verlag GmbH & Co. KGaA)A facile and low-cost approach is demonstrated for the fabrication of high-d. sub-1-nm gaps from Au nanoparticle monolayers as reproducible surface-enhanced Raman scattering (SERS) substrates. Au nanoparticles with larger diams. possess lower surface charge; the obtained large-area nanoparticle monolayer generates a high-d. of sub-1-nm gaps. A remarkable SERS performance with a 1011 magnitude for the Raman enhancement is achieved for 120 nm Au nanoparticle monolayers due to the dramatic increase in the electromagnetic field enhancement when the obtained gap is smaller than 0.5 nm. The Au nanoparticle monolayer is transferred onto a stretchable PDMS substrate and the structural stability and reproducibility of the high-d. sub-1-nm gaps in Au monolayer films are illustrated. The resultant Au nanoparticle monolayer substrates with an increasing particle diam. exhibit tunable plasmonic properties, which control the plasmon-enhanced photocatalytic efficiency for the dimerization of p-aminothiophenol. The findings reported here offer a new opportunity for expanding the SERS application.
- 53Liu, J.-W.; Zhang, S.-Y.; Qi, H.; Wen, W.-C.; Yu, S.-H. A General Strategy for Self-Assembly of Nanosized Building Blocks on Liquid/Liquid Interfaces. Small 2012, 8, 2412– 2420, DOI: 10.1002/smll.201200172Google Scholar53A General Strategy for Self-Assembly of Nanosized Building Blocks on Liquid/Liquid InterfacesLiu, Jian-Wei; Zhang, Shao-Yi; Qi, Hao; Wen, Wu-Cheng; Yu, Shu-HongSmall (2012), 8 (15), 2412-2420, S2412/1-S2412/5CODEN: SMALBC; ISSN:1613-6810. (Wiley-VCH Verlag GmbH & Co. KGaA)A family of water/oil interfaces is introduced to provide effective platforms for rapid fabrication of large-area self-assembled nanofilms composed of various nanosized building blocks, including nanoparticles (NPs), nanocubes (NC), nanowires (NWs), and nanosheets, at room temp. As a general interfacial assembly method, NWs and NPs are co-assembled at the liq./liq. interface. The as-prepd. co-assembled Ag NW and Ag NC films show high surface-enhanced Raman spectroscopy (SERS) intensity, the SERS performance being strongly dependent on the no. ratio of the two kinds of nanosized building blocks. The results demonstrate that this interfacial system provides a general method for the assembly of various nanosized building blocks with different shapes and dimensionalities, and thus paves an alternative pathway for further applications of macroscopic assemblies with different functionalities.
- 54Park, Y.-K.; Yoo, S.-H.; Park, S. Assembly of Highly Ordered Nanoparticle Monolayers at a Water/Hexane Interface. Langmuir 2007, 23, 10505– 10510, DOI: 10.1021/la701445aGoogle Scholar54Assembly of Highly Ordered Nanoparticle Monolayers at a Water/Hexane InterfacePark, Yong-Kyun; Yoo, Sang-Hoon; Park, SunghoLangmuir (2007), 23 (21), 10505-10510CODEN: LANGD5; ISSN:0743-7463. (American Chemical Society)This paper reports a methodol. for prepg. ordering hydrophilic metal nanoparticles into close-packed 2-dimensional arrays at a hexane-water interface with alkanethiol in the hexane layer. The destabilization of metal nanoparticles by the addn. of alc. caused the nanoparticles to adsorb to an interface where the surface of entrapped Au nanoparticle was in situ coated with the long-chain alkanethiols present in a hexane layer. The adsorption of alkanethiol to the nanoparticle surface caused the conversion of the electrostatic repulsive force to a van der Waals interaction, which is a key feature in forming highly ordered close-packed nanoparticle arrays.
- 55Reincke, F.; Hickey, S. G.; Kegel, W. K.; Vanmaekelbergh, D. Spontaneous Assembly of a Monolayer of Charged Gold Nanocrystals at the Water/Oil Interface. Angew. Chem., Int. Ed. 2004, 43, 458– 462, DOI: 10.1002/anie.200352339Google Scholar55Spontaneous assembly of a monolayer of charged gold nanocrystals at the water/oil interfaceReincke, Francois; Hickey, Stephen G.; Kegel, Willem K.; Vanmaekelbergh, DanielAngewandte Chemie, International Edition (2004), 43 (4), 458-462CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)Dense layers of individual, charged nanocrystals are formed at the aq./org. interface upon a slight redn. of the surface charge. The layers are remarkably robust, they creep up the glass. This method should be widely applicable to a broad range of charged colloids and will lead to the prodn. of new materials.
- 56Du, Y.; Wei, W.; Zhang, X.; Li, Y. Tuning Metamaterials Nanostructure of Janus Gold Nanoparticle Film for Surface-Enhanced Raman Scattering. J. Phys. Chem. C 2018, 122, 7997– 8002, DOI: 10.1021/acs.jpcc.8b00676Google Scholar56Tuning Metamaterials Nanostructure of Janus Gold Nanoparticle Film for Surface-Enhanced Raman ScatteringDu, Yixuan; Wei, Wei; Zhang, Xiaowei; Li, YunboJournal of Physical Chemistry C (2018), 122 (14), 7997-8002CODEN: JPCCCK; ISSN:1932-7447. (American Chemical Society)Large-area metamaterial nanostructures of a Janus gold nanoparticle (AuNP) film decorated with thiol-terminated polymers have been fabricated and tuned at an oil/water interface by a facile and innovative process. The results show that AuNPs had been arrayed with ultrasmall gaps between neighboring particles laminated with polymer which is called a Janus film. This film exhibits a sensitive property for surface-enhanced Raman scattering (SERS) for detn. of both hydrophilic methylene blue and hydrophobic thiram. The structure-dependent SERS of the Janus AuNP film has also been confirmed by a finite-difference time domain (FDTD) method.
- 57Li, J.; Wang, Q.; Wang, J.; Li, M.; Zhang, X.; Luan, L.; Li, P.; Xu, W. Quantitative SERS sensor based on self-assembled Au@Ag heterogeneous nanocuboids monolayer with high enhancement factor for practical quantitative detection. Anal. Bioanal. Chem. 2021, 413, 4207– 4215, DOI: 10.1007/s00216-021-03366-9Google ScholarThere is no corresponding record for this reference.
- 58Li, L.; Chin, W. S. Rapid Fabrication of a Flexible and Transparent Ag Nanocubes@PDMS Film as a SERS Substrate with High Performance. ACS Appl. Mater. & Interfaces 2020, 12, 37538– 37548, DOI: 10.1021/acsami.0c07178Google ScholarThere is no corresponding record for this reference.
- 59Cecchini, M. P.; Turek, V. A.; Paget, J.; Kornyshev, A. A.; Edel, J. B. Self-assembled nanoparticle arrays for multiphase trace analyte detection. Nat. Mater. 2013, 12, 165– 171, DOI: 10.1038/nmat3488Google Scholar59Self-assembled nanoparticle arrays for multiphase trace analyte detectionCecchini, Michael P.; Turek, Vladimir A.; Paget, Jack; Kornyshev, Alexei A.; Edel, Joshua B.Nature Materials (2013), 12 (2), 165-171CODEN: NMAACR; ISSN:1476-1122. (Nature Publishing Group)Nanoplasmonic structures designed for trace analyte detection using surface-enhanced Raman spectroscopy typically require sophisticated nanofabrication techniques. An alternative to fabricating such substrates is to rely on self-assembly of nanoparticles into close-packed arrays at liq./liq. or liq./air interfaces. The d. of the arrays can be controlled by modifying the nanoparticle functionality, pH of the soln. and salt concn. Importantly, these arrays are robust, self-healing, reproducible and extremely easy to handle. Here, the authors report on the use of such platforms formed by Au nanoparticles for the detection of multi-analytes from the aq., org. or air phases. The interfacial area of the Au array in the authors' system is ≈25 mm2 and can be made smaller, making this platform ideal for small-vol. samples, low concns. and trace analytes. Importantly, the ease of assembly and rapid detection make this platform ideal for in-the-field sample testing of toxins, explosives, narcotics or other hazardous chems.
- 60Turek, V. A.; Cecchini, M. P.; Paget, J.; Kucernak, A. R.; Kornyshev, A. A.; Edel, J. B. Plasmonic Ruler at the Liquid–Liquid Interface. ACS Nano 2012, 6, 7789– 7799, DOI: 10.1021/nn302941kGoogle Scholar60Plasmonic Ruler at the Liquid-Liquid InterfaceTurek, Vladimir A.; Cecchini, Michael P.; Paget, Jack; Kucernak, Anthony R.; Kornyshev, Alexei A.; Edel, Joshua B.ACS Nano (2012), 6 (9), 7789-7799CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)We report on a simple, fast, and inexpensive method to study adsorption and desorption of metallic nanoparticles at a liq./liq. interface. These interfaces provide an ideal platform for the formation of two-dimensional monolayers of nanoparticles, as they form spontaneously and are defect-correcting, acting as 2D "nanoparticle traps". Such two-dimensional, self-assembled nanoparticle arrays have a vast range of potential applications in displays, catalysis, plasmonic rulers, optoelectronics, sensors, and detectors. Here, we show that 16 nm diam. gold nanoparticles can be controllably adsorbed to a water/1,2-dichloroethane interface, and that we can control the av. interparticle spacing at the interface over the range 6-35 nm. The particle d. and av. interparticle spacing are exptl. assessed by measuring the optical plasmonic response of the nanoparticles in the bulk and at the interface and by comparing the exptl. data with existing theor. results.
- 61Velleman, L.; Sikdar, D.; Turek, V. A.; Kucernak, A. R.; Roser, S. J.; Kornyshev, A. A.; Edel, J. B. Tuneable 2D self-assembly of plasmonic nanoparticles at liquid|liquid interfaces. Nanoscale 2016, 8, 19229– 19241, DOI: 10.1039/C6NR05081FGoogle Scholar61Tuneable 2D self-assembly of plasmonic nanoparticles at liquid|liquid interfacesVelleman, Leonora; Sikdar, Debabrata; Turek, Vladimir A.; Kucernak, Anthony R.; Roser, Steve J.; Kornyshev, Alexei A.; Edel, Joshua B.Nanoscale (2016), 8 (46), 19229-19241CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)Understanding the structure and assembly of nanoparticles at liq.|liq. interfaces is paramount to their integration into devices for sensing, catalysis, electronics and optics. However, many difficulties arise when attempting to resolve the structure of such interfacial assemblies. In this article we use a combination of X-ray diffraction and optical reflectance to det. the structural arrangement and plasmon coupling between 12.8 nm diam. gold nanoparticles assembled at a water|1,2-dichloroethane interface. The liq.|liq. interface provides a molecularly flat and defect-correcting platform for nanoparticles to self-assemble. The amt. of nanoparticles assembling at the interface can be controlled via the concn. of electrolyte within either the aq. or org. phase. At higher electrolyte concn. more nanoparticles can settle at the liq.|liq. interface resulting in a decrease in nanoparticle spacing as obsd. from X-ray diffraction expts. The plasmonic coupling between the nanoparticles as they come closer together is obsd. by a red-shift in the optical reflectance spectra. The optical reflectance and the X-ray diffraction data are combined to introduce a new 'plasmon ruler'. This allows extn. of structural information from simple optical spectroscopy techniques, with important implications for understanding the structure of self-assembled nanoparticle films at liq. interfaces.
- 62Li, C.; Xu, Y.; Li, X.; Ye, Z.; Yao, C.; Chen, Q.; Zhang, Y.; Bell, S. E. J. Unexpected Dual Action of Cetyltrimethylammonium Bromide (CTAB) in the Self-Assembly of Colloidal Nanoparticles at Liquid–Liquid Interfaces. Adv. Mater. Interfaces 2020, 7, 2000391, DOI: 10.1002/admi.202000391Google Scholar62Unexpected Dual Action of Cetyltrimethylammonium Bromide (CTAB) in the Self-Assembly of Colloidal Nanoparticles at Liquid-Liquid InterfacesLi, Chunchun; Xu, Yikai; Li, Xinyuan; Ye, Ziwei; Yao, Chaoyi; Chen, Qinglu; Zhang, Yuanfeng; Bell, Steven E. J.Advanced Materials Interfaces (2020), 7 (14), 2000391CODEN: AMIDD2; ISSN:2196-7350. (Wiley-VCH Verlag GmbH & Co. KGaA)Self-assembly of colloidal nanoparticles at water-oil interfaces offers an efficient way to construct multi-dimensional arrays. Self-assembly is generally induced by using adsorbing mol. "modifiers" or co-solvents to remove the nanoparticles' surface charge. Here, it is shown that cetyltrimethylammonium bromide (CTAB), which is commonly used in bulk quantities in colloidal synthesis, can induce self-assembly of neg. charged colloidal nanoparticles at water-oil interfaces, even at sub-micromolar levels but it does this by providing charge screening rather than removing the surface charge. Since this is a phys. effect, CTAB can promote assembly of nanoparticles regardless of their morphol. or material compn. In the specific case of nanoparticles which allow CTAB to adsorb, such as Au, the self-assembly mechanism switches from charge screening to chem. adsorption as the concn. is increased. These both explain previous observations of spontaneous interfacial assembly and open up further possibilities for deliberately constructing functional nanoparticle arrays without the need for addnl. modifiers or co-solvents.
- 63Lin, X.; Fang, G.; Liu, Y.; He, Y.; Wang, L.; Dong, B. Marangoni Effect-Driven Transfer and Compression at Three-Phase Interfaces for Highly Reproducible Nanoparticle Monolayers. J. Phys. Chem. Lett. 2020, 11, 3573– 3581, DOI: 10.1021/acs.jpclett.0c01116Google Scholar63Marangoni Effect-Driven Transfer and Compression at Three-Phase Interfaces for Highly Reproducible Nanoparticle MonolayersLin, Xiang; Fang, Guoqiang; Liu, Yuanlan; He, Yangyang; Wang, Li; Dong, BinJournal of Physical Chemistry Letters (2020), 11 (9), 3573-3581CODEN: JPCLCD; ISSN:1948-7185. (American Chemical Society)Interfacial self-assembly is a powerful technol. for prepg. large scale nanoparticle monolayers, but fabrication of highly repeatable large scale nanoparticle monolayers remains a challenge. Here the authors develop an oil/H2O/oil (O/W/O) 3-phase system based on the Marangoni effect to fabricate highly reproducible nanoparticle monolayers. Nanoparticles could be easily transferred and compressed from the lower O/W interface to the upper O/W interface due to the interfacial tension gradient. The O/W/O system can be constructed using different kinds of org. solvents. Through this approach, good uniformity and reproducibility of the nanoparticle monolayers could be guaranteed even using a wide range of nanoparticle concns. Also, this strategy is generally applicable to various nanoparticles with different sizes, shapes, components, and surface ligands, which offers a facile and general approach to functional nanodevices.
- 64Konrad, M. P.; Doherty, A. P.; Bell, S. E. J. Stable and Uniform SERS Signals from Self-Assembled Two-Dimensional Interfacial Arrays of Optically Coupled Ag Nanoparticles. Anal. Chem. 2013, 85, 6783– 6789, DOI: 10.1021/ac4008607Google Scholar64Stable and Uniform SERS Signals from Self-Assembled Two-Dimensional Interfacial Arrays of Optically Coupled Ag NanoparticlesKonrad, Magdalena P.; Doherty, Andrew P.; Bell, Steven E. J.Analytical Chemistry (Washington, DC, United States) (2013), 85 (14), 6783-6789CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Densely packed interfacial nanoparticle films form spontaneously when aq. Ag colloid is shaken with CH2Cl2 in the presence of a "promoter" such as 10-4 mol dm-3 tetrabutylammonium nitrate (TBA+NO3-), which induces rapid self-assembly of the nanoparticles at the liq./liq. interface without adsorbing onto their surfaces. The particles within these reflective, metal-like liq. films (MeLLFs) are optically coupled and give strong SERS enhancement, similar to that obtained for the same colloid aggregated with optimized concn. of metal salt. However, unlike aggregated colloids, their structure means that they do not settle out of soln. so they give SERS spectra that are stable for >20 h and have good uniformity (relative std. deviation in abs. intensity over 1 mm2 array of 25 points was 1.1%). Since the films lie at the aq./org. interface, they are open to adsorption of analytes from either of the phases and can be probed in situ to detect both water- and non-water-sol. analytes. The detection limit for mercaptobenzoic acid (MBA) added to the org. layer was found to be <2 ppb. These materials therefore combine many of the best features of both patterned surfaces and metal colloids for quant. SERS anal.
- 65Xu, Y.; Konrad, M. P.; Lee, W. W. Y.; Ye, Z.; Bell, S. E. J. A Method for Promoting Assembly of Metallic and Nonmetallic Nanoparticles into Interfacial Monolayer Films. Nano Lett. 2016, 16, 5255– 5260, DOI: 10.1021/acs.nanolett.6b02418Google Scholar65A Method for Promoting Assembly of Metallic and Nonmetallic Nanoparticles into Interfacial Monolayer FilmsXu, Yikai; Konrad, Magdalena P.; Lee, Wendy W. Y.; Ye, Ziwei; Bell, Steven E. J.Nano Letters (2016), 16 (8), 5255-5260CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)Two-dimensional metal nanoparticle arrays are normally constructed at liq.-oil interfaces by modifying the surfaces of the constituent nanoparticles so that they self-assemble. Here we present a general and facile new approach for promoting such interfacial assembly without any surface modification. The method use salts that have hydrophobic ions of opposite charge to the nanoparticles, which sit in the oil layer and thus reduce the Coulombic repulsion between the particles in the org. phase, allowing the particles to sit in close proximity to each other at the interface. The advantage of this method is that because it does not require the surface of the particles to be modified it allows nonmetallic particles including TiO2 and SiO2 to be assembled into dense interfacial layers using the same procedure as is used for metallic particles. This opens up a route to a new family of nanostructured functional materials.
- 66Xu, Y.; Zhang, Y.; Li, C.; Ye, Z.; Bell, S. E. J. SERS as a Probe of Surface Chemistry Enabled by Surface-Accessible Plasmonic Nanomaterials. Acc. Chem. Res. 2023, 56, 2072– 2083, DOI: 10.1021/acs.accounts.3c00207Google Scholar66SERS as a Probe of Surface Chemistry Enabled by Surface-Accessible Plasmonic NanomaterialsXu, Yikai; Zhang, Yingrui; Li, Chunchun; Ye, Ziwei; Bell, Steven E. J.Accounts of Chemical Research (2023), 56 (15), 2072-2083CODEN: ACHRE4; ISSN:0001-4842. (American Chemical Society)A review. The efforts in the development of modifier-free synthetic approaches to synthesize surface-accessible, plasmonic nanomaterials for SERS are discussed. The definition of modifiers and surface-accessibility, esp. in the context of surface chem. studies in SERS, is established. As a general rule of thumb, the chem. ligands on surface-accessible nanomaterials should be easily displaceable by a wide range of target mols. relevant to potential applications. Modifier-free approaches for the bottom-up synthesis of colloidal nanoparticles, which are the basic building blocks for nanotechnol. are introduced. Modifier-free interfacial self-assembly approaches developed by the authors' group that allow the creation of multidimensional plasmonic nanoparticle arrays from different types of nanoparticle-building blocks are introduced. These multidimensional arrays can be further combined with different types of functional materials to form surface-accessible multifunctional hybrid plasmonic materials. Applications for surface-accessible nanomaterials as plasmonic substrates for SERS studies of surface chem. are demonstrated. The removal of modifiers led to significantly enhanced properties and the observation of new surface chem. phenomena that had been previously overlooked or misunderstood in the literature. Realizing the current limitations of modifier-based approaches provides new perspectives in manipulating mol.-metal interactions in nanotechnol. and can have significant implications in the design and synthesis of the next generation of nanomaterials.
- 67Shi, L.; Liu, M.; Zhang, L.; Tian, Y. A Liquid Interfacial SERS Platform on a Nanoparticle Array Stabilized by Rigid Probes for the Quantification of Norepinephrine in Rat Brain Microdialysates. Angew. Chem., Int. Ed. 2022, 61, e202117125, DOI: 10.1002/anie.202117125Google Scholar67A Liquid Interfacial SERS Platform on a Nanoparticle Array Stabilized by Rigid Probes for the Quantification of Norepinephrine in Rat Brain MicrodialysatesShi, Lu; Liu, Mengmeng; Zhang, Limin; Tian, YangAngewandte Chemie, International Edition (2022), 61 (21), e202117125CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)For the reliable detn. of trace chems. in the brain, we created a SERS platform based on a functionalized AuNPs array formed at a liq./liq. interface in a uniform fashion over a large substrate area through ternary regulations for real-time quantification of trace norepinephrine (NE). The rigid mol., 4-(thiophen-3-ylethynyl)-benzaldehyde (RP1) was designed and co-assembled at AuNPs with 4-mercaptophenylboronic acid (MPBA) to chem. define NE via dual recognition. Meanwhile, the rigid structure assembly of RP1 and MPBA efficiently fixed the interparticle gap, guaranteeing reproducible SERS anal. Furthermore, the Raman peak of C≃C group in the silent region was taken as a response element to further improve the accuracy. Combined with microdialysis, this SERS platform was developed for in-the-field testing of NE in rat brain microdialyzates following anxiety.
- 68Song, L.; Xu, B. B.; Cheng, Q.; Wang, X.; Luo, X.; Chen, X.; Chen, T.; Huang, Y. J. S. A. Instant interfacial self-assembly for homogeneous nanoparticle monolayer enabled conformal “lift-on” thin film technology. Science Advances 2021, 7, 2852, DOI: 10.1126/sciadv.abk2852Google ScholarThere is no corresponding record for this reference.
- 69Cong, T.; Wang, J.; Zhao, Y.; Zhang, D.; Fan, Z.; Pan, L. Tip-to-tip assembly of urchin-like Au nanostar at water-oil interface for surface-enhanced Raman spectroscopy detection. Anal. Chim. Acta 2021, 1154, 338323, DOI: 10.1016/j.aca.2021.338323Google Scholar69Tip-to-tip assembly of urchin-like Au nanostar at water-oil interface for surface-enhanced Raman spectroscopy detectionCong, Tianze; Wang, Jianzhen; Zhao, Yongpeng; Zhang, Dongmei; Fan, Zeng; Pan, LujunAnalytica Chimica Acta (2021), 1154 (), 338323CODEN: ACACAM; ISSN:0003-2670. (Elsevier B.V.)Au Nanostar (NS) monolayer as a surface enhanced Raman scattering (SERS) substrate was synthesized by self-assembly at a H2O-oil interface. It is confirmed from the expt. and simulation results that the Au NS monolayer includes lots of hot spots at or between the tips of the Au NSs, enhancing the local electromagnetic fields and giving rise to strong SERS signals sequentially. The limit of detection is down to 4.2 × 10-12 M for rhodamine 6G. Also, the Au NS monolayer can detect multiple mols., including thiabendazole, methylene blue, 4-mercaptobenzoic acid, and p-amino thiophenol, indicating that the SERS substrate composed of Au NS monolayer has potential applications in anal. chem., food safety, and environmental safety.
- 70Ma, Y.; Liu, H.; Mao, M.; Meng, J.; Yang, L.; Liu, J. Surface-Enhanced Raman Spectroscopy on Liquid Interfacial Nanoparticle Arrays for Multiplex Detecting Drugs in Urine. Anal. Chem. 2016, 88, 8145– 8151, DOI: 10.1021/acs.analchem.6b01884Google Scholar70Surface-Enhanced Raman Spectroscopy on Liquid Interfacial Nanoparticle Arrays for Multiplex Detecting Drugs in UrineMa, Yongmei; Liu, Honglin; Mao, Mei; Meng, Juan; Yang, Liangbao; Liu, JinhuaiAnalytical Chemistry (Washington, DC, United States) (2016), 88 (16), 8145-8151CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)The design and application of liq. interfacial plasmonic platform is still in its infancy but is an exciting topic in tunable optical devices, sensors, and catalysis. Here, we developed an interfacial surface-enhanced Raman scattering (SERS) platform through the large-scale self-assembly of gold nanoparticle (GNP) arrays at the cyclohexane (CYH)/water interface for detecting trace drug mols. in the urine of humans. The mols. extd. by the CYH phase from a urine sample were directly localized into the self-organized plasmonic hotspots, yielded excellent Raman enhancement, and realized the substrate-free interfacial SERS detection. Synchrotron radiation small-angle X-ray scattering (SR-SAXS) expts. reveals a good uniformity of approx. 2-3 nm interparticle distance in the GNP arrays. SERS colocalization expts. demonstrated that amphetamine mols. of different concn. levels could be loaded into the interfacial GNP arrays and realized the coassembly together with nanoparticles at the liq./liq. interface. Interfacial GNP arrays with dynamic nanogaps in liq. interfacial structure can make surrounding mols. easily diffuse into the nanogaps. In contrast, the fixed GNP arrays on Si wafer were more irregular, such as multilayer stack, random aggregates, and voids, during the drying process. When the drugs directly participate in the self-assembly process, it becomes easier for analytes diffusing into the nanogaps of GNP arrays, produces a concn. effect, and amplified the SERS sensitivity. This feature also enables mols. to be adsorbed evenly in the arrays and makes a more uniform distribution of both the analytes and GNPs in the liq. interface and realizes the significant increase in signal reproducibility. Interfacial SERS produced a std. deviation of 12.5% at 1001 cm-1 peak of methamphetamine (MAMP) mols. under the concn. of 1 ppm, implying a good reproducibility. Moreover, dual-analyte detection at org. and aq. phases was also realized and confirmed a good capability for analytes detection by liq. interfacial SERS platform, which promises nonengineering detection of analytes dissolved in often-inaccessible environments.
- 71Zhang, C.; You, E.; Jin, Q.; Yuan, Y.; Xu, M.; Ding, S.; Yao, J.; Tian, Z. Observing the dynamic “hot spots” on two-dimensional Au nanoparticles monolayer film. Chem. Commun. 2017, 53, 6788– 6791, DOI: 10.1039/C7CC03020GGoogle Scholar71Observing the dynamic "hot spots" on two-dimensional Au nanoparticles monolayer filmZhang, Chenjie; You, Enming; Jin, Qi; Yuan, Yaxian; Xu, Minmin; Ding, Songyuan; Yao, Jianlin; Tian, ZhongqunChemical Communications (Cambridge, United Kingdom) (2017), 53 (50), 6788-6791CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)Interparticle spacing was controlled by evapg. water on 2D Au nanoparticles arrays. Relationships among SERS effect, SPR catalysis, and gap distance were exptl. and theor. studied.
- 72Kelly, J.; Patrick, R.; Patrick, S.; Bell, S. E. J. Surface-Enhanced Raman Spectroscopy for the Detection of a Metabolic Product in the Headspace Above Live Bacterial Cultures. Angew. Chem., Int. Ed. 2018, 57, 15686– 15690, DOI: 10.1002/anie.201808185Google Scholar72Surface-Enhanced Raman Spectroscopy for the Detection of a Metabolic Product in the Headspace Above Live Bacterial CulturesKelly, Jessica; Patrick, Robin; Patrick, Sheila; Bell, Steven E. J.Angewandte Chemie, International Edition (2018), 57 (48), 15686-15690CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)In situ surface-enhanced Raman spectra of the headspace above cultures of six bacterial species showed strong characteristic bands from chemisorbed Me sulfide. This marker compd. is created by dissocn. of di-Me disulfide (DMDS), a fermentative metabolite of bacteria, on the surface of the enhancing Au or Ag nanoparticle films. Kinetic binding plots of media spiked with DMDS and of live cultures showed that the Au-based substrates were more suitable for the rapid detection of bacteria than Ag-based substrates. For E. coli DH5α, the sensitivity limit for headspace SERS detection was 1.5×107 CFU mL-1, which corresponded to detection 15 min after inoculation of the growth medium. Since the metabolites are only produced by viable bacteria, antibiotic (gentamicin) treatment stopped the normal signal growth of the marker peak. This work is a promising step towards rapid bedside detection of bacterial infections and rapid screening of antibiotics against bacteria.
- 73Li, C.; Zhang, Y.; Ye, Z.; Bell, S. E. J.; Xu, Y. Combining surface-accessible Ag and Au colloidal nanomaterials with SERS for in situ analysis of molecule–metal interactions in complex solution environments. Nat. Protoc 2023, 18, 2717– 2744, DOI: 10.1038/s41596-023-00851-6Google ScholarThere is no corresponding record for this reference.
- 74Zhong, Y.; Moore, T. C.; Dwyer, T.; Butrum-Griffith, A.; Allen, V. R.; Chen, J.; Wang, Y.; Cheng, F.; Glotzer, S. C.; Ye, X. Engineering and direct imaging of nanocube self-assembly pathways. Nature Chemical Engineering 2024, 1, 532– 541, DOI: 10.1038/s44286-024-00102-9Google ScholarThere is no corresponding record for this reference.
- 75Li, C.; Chai, L.; Chen, Q.; Ye, Z.; Xu, Y.; Bell, S. E. J. Superhydrophobic needles tipped with 2-dimensional arrays of plasmonic colloidal nanoparticles for microdroplet SERS analysis. J. Raman Spectrosc. 2021, 52, 386– 393, DOI: 10.1002/jrs.5992Google Scholar75Superhydrophobic needles tipped with 2-dimensional arrays of plasmonic colloidal nanoparticles for microdroplet SERS analysisLi, Chunchun; Chai, Lin; Chen, Qinglu; Ye, Ziwei; Xu, Yikai; Bell, Steven E. J.Journal of Raman Spectroscopy (2021), 52 (2), 386-393CODEN: JRSPAF; ISSN:0377-0486. (John Wiley & Sons Ltd.)Aq. microdroplets strongly attach to metallic needles with superhydrophobic sides and flat hydrophilic tips. Such needles can be made surface-enhanced Raman spectroscopy (SERS)-active by adsorbing a layer of densely packed and uniform plasmonic nanoparticles onto the hydrophilic tip. The resulting particle-tipped needles allow dual enhancement of the Raman signals from microdroplets of low concn. analytes by combining analyte enrichment through solvent evapn. and plasmonic SERS enhancement. The combination of small sample vol., preconcn., and SERS allows extremely low total amts. of analytes to be detected. Here, we show that with crystal violet as the model analyte, the limit of detection can reach 2 pg. The method can be readily used to fabricate superhydrophobic needles tipped with different types of plasmonic colloidal nanoparticles for enhanced Raman anal., for example, silver cube tipped needles could be used to detect as little as 2.5 ng of trinitrotoluene.
- 76Zhang, L.; Li, X.; Liu, W.; Hao, R.; Jia, H.; Dai, Y.; Usman Amin, M.; You, H.; Li, T.; Fang, J. Highly active Au NP microarray films for direct SERS detection. Journal of Materials Chemistry C 2019, 7, 15259– 15268, DOI: 10.1039/C9TC04848KGoogle ScholarThere is no corresponding record for this reference.
- 77Kim, K.; Han, H. S.; Choi, I.; Lee, C.; Hong, S.; Suh, S.-H.; Lee, L. P.; Kang, T. Interfacial liquid-state surface-enhanced Raman spectroscopy. Nat. Commun. 2013, 4, 2182, DOI: 10.1038/ncomms3182Google Scholar77Interfacial liquid-state surface-enhanced Raman spectroscopyKim Kihoon; Han Hye Soo; Choi Inhee; Lee Chiwon; Hong SoonGweon; Suh Sang-Hee; Lee Luke P; Kang TaewookNature communications (2013), 4 (), 2182 ISSN:.Oriented assemblies of functional nanoparticles, with the aid of external physical and chemical driving forces, have been prepared on two-dimensional solid substrates. It is challengeable, however, to achieve three-dimensional assembly directly in solution, owing to thermal fluctuations and free diffusion. Here we describe the self-orientation of gold nanorods at an immiscible liquid interface (that is, oleic acid-water) and exploit this novel phenomenon to create a substrate-free interfacial liquid-state surface-enhanced Raman spectroscopy. Dark-field imaging and Raman scattering results reveal that gold nanorods spontaneously adopt a vertical orientation at an oleic acid-water interface in a stable trapping mode, which is in good agreement with simulation results. The spontaneous vertical alignment of gold nanorods at the interface allows one to accomplish significant additional amplification of the Raman signal, which is up to three to four orders of magnitude higher than that from a solution of randomly oriented gold nanorods.
- 78Zhang, K.; Zhao, J.; Xu, H.; Li, Y.; Ji, J.; Liu, B. Multifunctional Paper Strip Based on Self-Assembled Interfacial Plasmonic Nanoparticle Arrays for Sensitive SERS Detection. ACS Appl. Mater. & Interfaces 2015, 7, 16767– 16774, DOI: 10.1021/acsami.5b04534Google ScholarThere is no corresponding record for this reference.
- 79Luo, W.; Wu, C.; Huang, S.; Luo, X.; Yuan, R.; Yang, X. Liquid Phase Interfacial Surface-Enhanced Raman Scattering Platform for Ratiometric Detection of MicroRNA 155. Anal. Chem. 2020, 92, 15573– 15578, DOI: 10.1021/acs.analchem.0c03633Google Scholar79Liquid Phase Interfacial Surface-Enhanced Raman Scattering Platform for Ratiometric Detection of MicroRNA 155Luo, Wei; Wu, Caijun; Huang, Siqi; Luo, Xiliang; Yuan, Ruo; Yang, XiaAnalytical Chemistry (Washington, DC, United States) (2020), 92 (23), 15573-15578CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)The self-assembly of gold nanoparticles (Au NPs) on a liq. phase interface is often employed as a surface-enhanced Raman scattering (SERS) platform with advantages of simple prepn., high reproducibility, and a defect-free character, but they are limited to only detect a target with Raman signals. To overcome this problem, microRNA 155 without a Raman signal can be detected by a liq. phase interfacial ratiometric SERS platform. Compared with the typical solid phase SERS platform, we propose a distinctive strategy not only owning the advantages of the liq. phase interfacial platform but also breaking the limitation of recent liq.-liq. interfacial SERS anal. This platform presents a fabulous sensitivity with a limit of detection (LOD) of 1.10 aM for microRNA 155. By simply altering the duplex-specific nuclease (DSN) enzyme amplification, our strategy can realize detection of a variety of microRNAs, paving the way to practical applications of a liq. phase SERS platform.
- 80Dong, J.; Yang, C.; Wu, H.; Wang, Q.; Cao, Y.; Han, Q.; Gao, W.; Wang, Y.; Qi, J.; Sun, M. Two-Dimensional Self-Assembly of Au@Ag Core–Shell Nanocubes with Different Permutations for Ultrasensitive SERS Measurements. ACS Omega 2022, 7, 3312– 3323, DOI: 10.1021/acsomega.1c05452Google Scholar80Two-Dimensional Self-Assembly of Au@Ag Core-Shell Nanocubes with Different Permutations for Ultrasensitive SERS MeasurementsDong, Jun; Yang, Chengyuan; Wu, Haoran; Wang, Qianying; Cao, Yi; Han, Qingyan; Gao, Wei; Wang, Yongkai; Qi, Jianxia; Sun, MengtaoACS Omega (2022), 7 (4), 3312-3323CODEN: ACSODF; ISSN:2470-1343. (American Chemical Society)Different self-assembly methods not only directly change the arrangement of noble metal particles on the substrate but also indirectly affect the local electromagnetic field distribution and intensity of the substrate under specific optical excitation conditions, which leads to distinguished different enhancement effects of the structure on mol. Raman signals. In this paper, first, the gold species growth method was used to prep. the silver-coated gold nanocubes (Au@Ag NCs) with regular morphol. and uniform size, and then the two-phase and three-phase liq.-liq. self-assembly and evapn.-induced self-assembly methods were used to obtain the substrate structure with different NC arrangement patterns. The optimal arrangement of NCs was found by transverse comparison of Raman signal detection of probe mols. with the same concn. Subsequently, surface-enhanced Raman scattering (SERS) measurements of Rhodamine (Rh6G) and aspartame (APM) were carried out. Furthermore, the finite element method (FEM) was employed to calc. the local electromagnetic fields of the substrates with different Au@Ag NC arrangements, and the calcd. results were in agreement with the exptl. results. The exptl. results show that the SERS-active substrate was largely assocd. with the different arrangements of Au@Ag NCs, and the island membrane Au@Ag NCs array substrate obtained by evapn.-induced self-assembly can generate a strong local electromagnetic field due to the edge and corner bonding gap between the tightly arranged NCs; this endows the substrate with benign sensitivity and reproducibility and has great potential in mol. detection, biosensing, and food safety monitoring.
- 81Chen, X.; Cui, A.; He, M.; Yan, M.; Zhang, X.; Ruan, J.; Yang, S. Slippery Au Nanosphere Monolayers with Analyte Enrichment and SERS Enhancement Functions. Nano Lett. 2023, 23, 6736– 6743, DOI: 10.1021/acs.nanolett.3c02238Google ScholarThere is no corresponding record for this reference.
- 82Zhang, K.; Ji, J.; Li, Y.; Liu, B. Interfacial Self-Assembled Functional Nanoparticle Array: A Facile Surface-Enhanced Raman Scattering Sensor for Specific Detection of Trace Analytes. Anal. Chem. 2014, 86, 6660– 6665, DOI: 10.1021/ac501383xGoogle Scholar82Interfacial Self-Assembled Functional Nanoparticle Array: A Facile Surface-Enhanced Raman Scattering Sensor for Specific Detection of Trace AnalytesZhang, Kun; Ji, Ji; Li, Yixin; Liu, BaohongAnalytical Chemistry (Washington, DC, United States) (2014), 86 (13), 6660-6665CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Surface-enhanced Raman scattering (SERS) has proven to be promising for the detection of trace analytes; however, the precise nanofabrication of a specific and sensitive plasmonic SERS-active substrate is still a major challenge that limits the scope of its applications. In this work, gold nanoparticles are self-assembled into densely packed two-dimensional arrays at a liq./liq. interface between di-Me carbonate and water in the absence of template controller mols. Both the simulation and expt. results show that the particles within these film-like arrays exhibit strong electromagnetic coupling and enable large amplification of Raman signals. In order to realize the level of sensing specificity, the surface chem. of gold nanoparticles (Au NPs) is rationally tailored by incorporating an appropriate chem. moiety that specifically captures mols. of interest. The ease of fabrication and good uniformity make this platform ideal for in situ SERS sensing of trace targets in complex samples.
- 83Lee, Y. H.; Shi, W.; Lee, H. K.; Jiang, R.; Phang, I. Y.; Cui, Y.; Isa, L.; Yang, Y.; Wang, J.; Li, S.; Ling, X. Y. Nanoscale surface chemistry directs the tunable assembly of silver octahedra into three two-dimensional plasmonic superlattices. Nat. Commun. 2015, 6, 6990, DOI: 10.1038/ncomms7990Google Scholar83Nanoscale surface chemistry directs the tunable assembly of silver octahedra into three two-dimensional plasmonic superlatticesLee, Yih Hong; Shi, Wenxiong; Lee, Hiang Kwee; Jiang, Ruibin; Phang, In Yee; Cui, Yan; Isa, Lucio; Yang, Yijie; Wang, Jianfang; Li, Shuzhou; Ling, Xing YiNature Communications (2015), 6 (), 6990CODEN: NCAOBW; ISSN:2041-1723. (Nature Publishing Group)A major challenge in nanoparticle self-assembly is programming the large-area organization of a single type of anisotropic nanoparticle into distinct superlattices with tunable packing efficiencies. Here we utilize nanoscale surface chem. to direct the self-assembly of silver octahedra into three distinct two-dimensional plasmonic superlattices at a liq./liq. interface. Systematically tuning the surface wettability of silver octahedra leads to a continuous superlattice structural evolution, from close-packed to progressively open structures. Notably, silver octahedra standing on vertices arranged in a square lattice is obsd. using hydrophobic particles. Simulations reveal that this structural evolution arises from competing interfacial forces between the particles and both liq. phases. Structure-to-function characterizations reveal that the standing octahedra array generates plasmonic 'hotstrips', leading to nearly 10-fold more efficient surface-enhanced Raman scattering compared with the other more densely packed configurations. The ability to assemble these superlattices on the wafer scale over various platforms further widens their potential applications.
- 84Zhao, W.; Zhang, Y.; Yang, J.; Li, J.; Feng, Y.; Quan, M.; Yang, Z.; Xiao, S. Synergistic plasmon resonance coupling and light capture in ordered nanoarrays as ultrasensitive and reproducible SERS substrates. Nanoscale 2020, 12, 18056– 18066, DOI: 10.1039/D0NR02972FGoogle Scholar84Synergistic plasmon resonance coupling and light capture in ordered nanoarrays as ultrasensitive and reproducible SERS substratesZhao, Weidong; Zhang, Yuxian; Yang, Jiajia; Li, Jinming; Feng, Yun; Quan, Maohua; Yang, Zhou; Xiao, ShuyuanNanoscale (2020), 12 (35), 18056-18066CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)An effective SERS substrate for on-field detection needs to satisfy high sensitivity to analyte and signal reproducibility even in the special case of tilting or bending of substrates. Herein, we transferred monolayer AuNPs into a nanocavity to construct a Au particle-in-hemispherical honeycomb nanoarray (PIHHN) as an ultrasensitive and spatially reproducible SERS substrate. The capacity of detection for R6G in an optimal PIHHN substrate is as low as a concn. of 10-15 M, and the RSD of signal deviation is no more than 5.6%. FDTD simulations explain that placing AuNPs into a metallic nanocavity can capture and focus the light field to improve the interaction between the light and the substrate and provide the collective effect of multiple plasmon coupling, which can induce a stronger electromagnetic field. In addn., the system can generate more hot spots between AuNPs and between AuNPs and the metallic nanocavity. In particular, when the substrate is tilted or bent at an angle from 0° to 60°, the SERS performance remains stable due to the rotational symmetry of the PIHHN structure, which demonstrates the capability of on-field detection. Furthermore, the PIHHN substrate is employed as a highly sensitive multiplex sensor in on-field anal. for contaminated soil, achieving the detection of analytes down to 0.5 ppb.
- 85Su, M.; Jiang, Q.; Guo, J.; Zhu, Y.; Cheng, S.; Yu, T.; Du, S.; Jiang, Y.; Liu, H. Quality alert from direct discrimination of polycyclic aromatic hydrocarbons in edible oil by liquid-interfacial surface-enhanced Raman spectroscopy. LWT 2021, 143, 111143, DOI: 10.1016/j.lwt.2021.111143Google ScholarThere is no corresponding record for this reference.
- 86Lee, Y. H.; Lee, C. K.; Tan, B.; Rui Tan, J. M.; Phang, I. Y.; Ling, X. Y. Using the Langmuir–Schaefer technique to fabricate large-area dense SERS-active Au nanoprism monolayer films. Nanoscale 2013, 5, 6404– 6412, DOI: 10.1039/c3nr00981eGoogle Scholar86Using the Langmuir-Schaefer technique to fabricate large-area dense SERS-active Au nanoprism monolayer filmsLee, Yih Hong; Lee, Choon Keong; Tan, Baorui; Tan, Joel Ming Rui; Phang, In Yee; Ling, Xing YiNanoscale (2013), 5 (14), 6404-6412CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)Interfacial self-assembly of nanoparticles is capable of creating large-area close-packed structures for a variety of applications. However, monolayers of hydrophilic cetyltrimethylammonium bromide (CTAB)-coated Au nanoparticles are challenging to assemble via interfacial self-assembly. This report presents a facile and scalable process to fabricate large-area monolayer films of ultrathin CTAB-coated Au nanoprisms at the air-water interface using the Langmuir-Schaefer technique. This is first achieved by a one-step functionalization of Au nanoprisms with poly(vinylpyrrolidone) (PVP). PVP functionalization is completed within a short time without loss of nanoprisms due to aggregation. Uniform and near close-packed monolayers of the Au nanoprisms formed over large areas (∼1 cm2) at the air-water interface can be transferred to substrates with different wettabilities. The inter-prism gaps are tuned qual. through the introduction of dodecanethiol and oleylamine. The morphol. integrity of the nanoprisms is maintained throughout the entire assembly process, without truncation of the nanoprism tips. The near close-packed arrangement of the nanoprism monolayers generates large nos. of hot spots in the 2D arrays in the tip-to-tip and edge-to-edge inter-particle regions, giving rise to strong surface-enhanced Raman scattering (SERS) signals. When deposited on an Au mirror film, addnl. hotspots are created in the 3rd dimension in the gaps between the 2D nanoprism monolayers and the Au film. SERS enhancement factors reaching 104 for non-resonant probe mols. are achieved.
- 87Zhang, H.; Wei, J.; Zhang, X.-G.; Zhang, Y.-J.; Radjenovica, P. M.; Wu, D.-Y.; Pan, F.; Tian, Z.-Q.; Li, J.-F. Plasmon-Induced Interfacial Hot-Electron Transfer Directly Probed by Raman Spectroscopy. Chem. 2020, 6, 689– 702, DOI: 10.1016/j.chempr.2019.12.015Google Scholar87Plasmon-Induced Interfacial Hot-Electron Transfer Directly Probed by Raman SpectroscopyZhang, Hua; Wei, Jie; Zhang, Xia-Guang; Zhang, Yue-Jiao; Radjenovica, Petar M.; Wu, De-Yin; Pan, Feng; Tian, Zhong-Qun; Li, Jian-FengChem (2020), 6 (3), 689-702CODEN: CHEMVE; ISSN:2451-9294. (Cell Press)Plasmon-mediated photocatalysis via hot-electron transfer attracts increasing interest due to its capability to improve energy utilization efficiency. However, more insightful information is still needed to reveal the mechanism of interfacial hot-electron transfer. Herein, the plasmon-induced hot-electron transfer at different plasmonic interfaces, including Au-insulator (SiO2), Au-semiconductor (TiO2 and Cu2O), and Au-metal (Pd and Pt), is directly investigated using surface-enhanced Raman spectroscopy (SERS) and d. functional theory calcn. with a (sub)nanometer spatial resoln., through the fabrication of well-defined plasmonic nanostructures. (Sub)nanometer-distance dependence of interfacial hot-electron transfer has been identified for the first time. Hot electrons can migrate across the Au-semiconductor or Au-metal interfaces and transfer more than 10 nm in semiconductors but decay to thermally equilibrated states rapidly in metals in less than 1 nm. Such a transfer process is blocked at the Au-insulator interface. This work promotes the fundamental understanding of plasmon-induced hot-electron transmission and photocatalysis at plasmonic interfaces.
- 88Liu, H. L.; Yang, Z. L.; Meng, L.; Sun, Y.; Wang, J.; Yang, L.; Liu, J.; Tian, Z. Three-Dimensional and Time-Ordered Surface-Enhanced Raman Scattering Hotspot Matrix. J. Am. Chem. Soc. 2014, 136, 5332– 5341, DOI: 10.1021/ja501951vGoogle Scholar88Three-Dimensional and Time-Ordered Surface-Enhanced Raman Scattering Hotspot MatrixLiu, Honglin; Yang, Zhilin; Meng, Lingyan; Sun, Yudie; Wang, Jie; Yang, Liangbao; Liu, Jinhuai; Tian, ZhongqunJournal of the American Chemical Society (2014), 136 (14), 5332-5341CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)The "fixed" or "flexible" design of plasmonic hotspots is a frontier area of research in the field of surface-enhanced Raman scattering (SERS). Most reported SERS hotspots have been shown to exist in zero-dimensional point-like, one-dimensional linear, or two-dimensional planar geometries. Here, we demonstrate a novel three-dimensional (3D) hotspot matrix that can hold hotspots between every two adjacent particles in 3D space, simply achieved by evapg. a droplet of citrate-Ag sols on a fluorosilylated silicon wafer. In situ synchrotron-radiation small-angle X-ray scattering (SR-SAXS), combined with dark-field microscopy and in situ micro-UV, was employed to explore the evolution of the 3D geometry and plasmonic properties of Ag nanoparticles in a single droplet. In such a droplet, there is a distinct 3D geometry with minimal polydispersity of particle size and maximal uniformity of interparticle distance, significantly different from the dry state. According to theor. simulations, the liq. adhesive force promotes a closely packed assembly of particles, and the interparticle distance is not fixed but can be balanced in a small range by the interplay of the van der Waals attraction and electrostatic repulsion experienced by a particle. The "trapping well" for immobilizing particles in 3D space can result in a large no. of hotspots in a 3D geometry. Both theor. and exptl. results demonstrate that the 3D hotspots are predictable and time-ordered in the absence of any sample manipulation. Use of the matrix not only produces giant Raman enhancement at least 2 orders of magnitude larger than that of dried substrates, but also provides the structural basis for trapping mols. Even a single mol. of resonant dye can generate a large SERS signal. With a portable Raman spectrometer, the detection capability is also greatly improved for various analytes with different natures, including pesticides and drugs. This 3D hotspot matrix overcomes the long-standing limitations of SERS for the ultrasensitive characterization of various substrates and analytes and promises to transform SERS into a practical anal. technique.
- 89Ge, M. H.; Li, P.; Cao, C. T.; Li, S. F.; Lin, D. Y.; Yang, L. B. A long-period and high-stability three-dimensional surface-enhanced Raman scattering hotspot matrix. Chem. Commun. 2019, 55, 8647– 8650, DOI: 10.1039/C9CC02980JGoogle Scholar89A long-period and high-stability three-dimensional surface-enhanced Raman scattering hotspot matrixGe, Meihong; Li, Pan; Cao, Chentai; Li, Shaofei; Lin, Dongyue; Yang, LiangbaoChemical Communications (Cambridge, United Kingdom) (2019), 55 (59), 8647-8650CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)A novel long-period and high-stability 3D hotspot matrix was constructed with the assistance of glycerol based on our previous study on the dynamic-SERS approach in the water system: it could increase efficient hotspot duration from few seconds to twenty minutes and strongly improve sensitivity and reproducibility for SERS detection.
- 90Chen, X.; Ding, Q.; Bi, C.; Ruan, J.; Yang, S. Lossless Enrichment of Trace Analytes in Levitating Droplets for Multiphase and Multiplex Detection. Nat. Commun. 2022, 13, 7807, DOI: 10.1038/s41467-022-35495-9Google Scholar90Lossless enrichment of trace analytes in levitating droplets for multiphase and multiplex detectionChen, Xueyan; Ding, Qianqian; Bi, Chao; Ruan, Jian; Yang, ShikuanNature Communications (2022), 13 (1), 7807CODEN: NCAOBW; ISSN:2041-1723. (Nature Portfolio)Concg. a trace amt. of mols. from liqs., solid objects, or the gas phase and delivering them to a localized area are crucial for almost any trace analyte detection device. Analytes within a liq. droplet resting on micro/nanostructured surfaces with liq.-repellent coatings can be concd. during solvent evapn. However, these coatings suffer from complex manufg. procedures, poor versatility, and limited analyte enrichment efficiency. Here, we report on the use of an acoustic levitation platform to losslessly conc. the analyte mols. dissolved in any volatile liq., attached to solid objects, or spread in air. Gold nanoparticles can be simultaneously concd. with the analytes in different phases, realizing sensitive, surface-enhanced Raman scattering detection even at attomolar (10-18 mol/L) concn. levels. The acoustic levitation platform-enabled, lossless analyte enrichment can significantly increase the anal. performance of many conventional microsensing techniques.
- 91Yang, L. B.; Li, P.; Liu, H. L.; Tang, X. H.; Liu, J. H. A dynamic surface enhanced Raman spectroscopy method for ultra-sensitive detection: from the wet state to the dry state. Chem. Soc. Rev. 2015, 44, 2837– 2848, DOI: 10.1039/C4CS00509KGoogle Scholar91A dynamic surface enhanced Raman spectroscopy method for ultra-sensitive detection: from the wet state to the dry stateYang, Liangbao; Li, Pan; Liu, Honglin; Tang, Xianghu; Liu, JinhuaiChemical Society Reviews (2015), 44 (10), 2837-2848CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)Surface-enhanced Raman spectroscopy (SERS) has been demonstrated to be an excellent anal. tool for a wide range of research and practical applications owing to its ability to achieve highly sensitive detection and provide fingerprint information for analytes. Improving the sensitivity of SERS is beneficial for the rapid anal. of target mols. in various systems, where the ultimate goal is to obtain quant. anal. and detection. Considerable efforts have been made to develop new methods for SERS detection that improve upon its high sensitivity and reproducibility. In this tutorial review, we first introduce the traditional methods for SERS detection and then report in detail on the features of a new strategy for implementing SERS. This new method, namely, a dynamic surface-enhanced Raman spectroscopy method proposed by our group, is based on state translation nanoparticle-enhanced Raman spectroscopy (STNERS) from the wet state to the dry state. Notably, during this process, a three-dimensional (3D) hotspot matrix that can hold hotspots between every two adjacent particles in 3D space, with minimal polydispersity of the particle size and maximal uniformity of the interparticle distance, can be simply achieved. Expts. and applications using STNERS are reviewed starting with an investigation of STNERS mechanisms and a discussion of sample prepn. Next, evidence of the advantages of STNERS and practical applications are discussed. Finally, the future outlook for STNERS and the development of STNERS as an ultra-sensitive detection method are also discussed.
- 92Zhou, G. L.; Li, P.; Ge, M. H.; Wang, J. P.; Chen, S. Y.; Nie, Y. M.; Wang, Y. X.; Qin, M.; Huang, G. Y.; Lin, D. Y.; Wang, H. Z.; Yang, L. B. Controlling the Shrinkage of 3D Hot Spot Droplets as a Microreactor for Quantitative SERS Detection of Anticancer Drugs in Serum Using a Handheld Raman Spectrometer. Anal. Chem. 2022, 94, 4831– 4840, DOI: 10.1021/acs.analchem.2c00071Google Scholar92Controlling the Shrinkage of 3D Hot Spot Droplets as a Microreactor for Quantitative SERS Detection of Anticancer Drugs in Serum Using a Handheld Raman SpectrometerZhou, Guoliang; Li, Pan; Ge, Meihong; Wang, Junping; Chen, Siyu; Nie, Yuman; Wang, Yaoxiong; Qin, Miao; Huang, Guangyao; Lin, Dongyue; Wang, Hongzhi; Yang, LiangbaoAnalytical Chemistry (Washington, DC, United States) (2022), 94 (11), 4831-4840CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Quant. measurement is one of the ultimate targets for surface-enhanced Raman spectroscopy (SERS), but it suffers from difficulties in controlling the uniformity of hot spots and placing the target mols. in the hot spot space. Here, a convenient approach of three-phase equil. controlling the shrinkage of three-dimensional (3D) hot spot droplets has been demonstrated for the quant. detection of the anticancer drug 5-fluorouracil (5-FU) in serum using a handheld Raman spectrometer. Droplet shrinkage, triggered by the shaking of aq. nanoparticle (NP) colloids with immiscible oil chloroform (CHCl3) after the addn. of neg. ions and acetone, not only brings the nanoparticles in close proximity but can also act as a microreactor to enhance the spatial enrichment capability of the analyte in plasmonic sites and thereby realize simultaneously controlling 3D hot spots and placing target mols. in hot spots. Moreover, the shrinking process of Ag colloid droplets has been investigated using a high-speed camera, an in situ transmission electron microscope (in situ TEM), and a dark-field microscope (DFM), demonstrating the high stability and uniformity of nanoparticles in droplets. The shrunk Ag NP droplets exhibit excellent SERS sensitivity and reproducibility for the quant. anal. of 5-FU over a large range of 50-1000 ppb. Hence, it is promising for quant. anal. of complex systems and long-term monitoring of bioreactions.
- 93Ge, M. H.; Li, P.; Zhou, G. L.; Chen, S. Y.; Han, W.; Qin, F.; Nie, Y. M.; Wang, Y. X.; Qin, M.; Huang, G. Y.; Li, S. F.; Wang, Y. T.; Yang, L. B.; Tian, Z. Q. General Surface-Enhanced Raman Spectroscopy Method for Actively Capturing Target Molecules in Small Gaps. J. Am. Chem. Soc. 2021, 143, 7769– 7776, DOI: 10.1021/jacs.1c02169Google Scholar93General Surface-Enhanced Raman Spectroscopy Method for Actively Capturing Target Molecules in Small GapsGe, Meihong; Li, Pan; Zhou, Guoliang; Chen, Siyu; Han, Wei; Qin, Feng; Nie, Yuman; Wang, Yaoxiong; Qin, Miao; Huang, Guangyao; Li, Shaofei; Wang, Yongtao; Yang, Liangbao; Tian, ZhongqunJournal of the American Chemical Society (2021), 143 (20), 7769-7776CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Over the past decade, many efforts have been devoted to designing and fabricating substrates for surface-enhanced Raman spectroscopy (SERS) with abundant hot spots to improve the sensitivity of detection. However, there have been many difficulties involved in causing mols. to enter hot spots actively or effectively. Here, we report a general SERS method for actively capturing target mols. in small gaps (hot spots) by constructing a nanocapillary pumping model. The ubiquity of hot spots and the inevitability of mols. entering them lights up all the hot spots and makes them effective. This general method can realize the highly sensitive detection of different types of mols., including org. pollutants, drugs, poisons, toxins, pesticide residues, dyes, antibiotics, amino acids, antitumor drugs, explosives, and plasticizers. Addnl., in the dynamic detection process, an efficient and stable signal can be maintained for 1-2 min, which increases the practicality and operability of this method. Moreover, a dynamic detection process like this corresponds to the processes of material transformation in some organisms, so the method can be used to monitor transformation processes such as the death of a single cell caused by photothermal stimulation. Our method provides a novel pathway for generating hot spots that actively attract target mols., and it can achieve general ultratrace detection of diverse substances and be applied to the study of cell behaviors in biol. systems.
- 94Wang, W.; Pu, S.; Hu, W.; Gu, J.; Ren, B.; Tian, Z.; Liu, G. Revealing the synergistic effect of capillary force and electrostatic attraction for D-SERS sensitivity. Chem. Commun. (Camb) 2022, 58, 3953– 3956, DOI: 10.1039/D2CC00824FGoogle ScholarThere is no corresponding record for this reference.
- 95Qin, M.; Ge, M.; Li, P.; Chen, S.; Huang, G.; Tong, X.; Han, W.; Ren, D.; He, Y.; Lin, D.; Yang, L.; Tian, Z. Natural < 3 nm Interbedded Gaps to Trap Target Molecules and Provide an Enhanced Raman Spectroscopy Method. Advanced Optical Materials 2022, 10, 2200551, DOI: 10.1002/adom.202200551Google ScholarThere is no corresponding record for this reference.
- 96Chen, S.; Ge, M.; Weng, S.; Li, J.; Huang, Y.; Li, P.; Yang, L. Development of a MoS(2)/Ag NP Nanopocket to Trap Target Molecules for Surface-Enhanced Raman Scattering Detection with Long-Term Stability and High Sensitivity. Anal. Chem. 2023, 95, 10257– 10264, DOI: 10.1021/acs.analchem.3c00665Google ScholarThere is no corresponding record for this reference.
- 97Deegan, R. D.; Bakajin, O.; Dupont, T. F.; Huber, G.; Nagel, S. R.; Witten, T. A. Capillary Flow as the Cause of Ring Stains from Dried Liquid Drops. Nature 1997, 389, 827– 829, DOI: 10.1038/39827Google Scholar97Capillary flow as the cause of ring stains from dried liquid dropsDeegan, Robert D.; Bakajin, Olgica; Dupont, Todd F.; Huber, Greg; Nagel, Sidney R.; Witten, Thomas A.Nature (London) (1997), 389 (6653), 827-829CODEN: NATUAS; ISSN:0028-0836. (Macmillan Magazines)When a spilled drop of coffee dries on a solid surface, it leaves a dense, ring-like deposit along the perimeter. The coffee - initially dispersed over the entire drop - becomes concd. into a tiny fraction of it. Such ring deposits are common wherever drops contg. dispersed solids evap. on a surface, and they influence processes such as printing, washing and coating. Ring deposits also provide a potential means to write or deposit a fine pattern onto a surface. Here we ascribe the characteristic pattern of the deposition to a form of capillary flow in which pinning of the contact line of the drying drop ensures that liq. evapg. from the edge is replenished by liq. from the interior. The resulting outward flow can carry virtually all the dispersed material to the edge. This mechanism predicts a distinctive power-law growth of the ring mass with time - a law independent of the particular substrate, carrier fluid or deposited solids. We have verified this law by microscopic observations of colloidal fluids.
- 98De Angelis, F.; Gentile, F.; Mecarini, F.; Das, G.; Moretti, M.; Candeloro, P.; Coluccio, M. L.; Cojoc, G.; Accardo, A.; Liberale, C.; Zaccaria, R. P.; Perozziello, G.; Tirinato, L.; Toma, A.; Cuda, G.; Cingolani, R.; Di Fabrizio, E. Breaking the Diffusion Limit with Super-Hydrophobic Delivery of Molecules to Plasmonic Nanofocusing SERS Structures. Nat. Photonics 2011, 5, 682– 687, DOI: 10.1038/nphoton.2011.222Google Scholar98Breaking the diffusion limit with super-hydrophobic delivery of molecules to plasmonic nanofocusing SERS structuresDe Angelis, F.; Gentile, F.; Mecarini, F.; Das, G.; Moretti, M.; Candeloro, P.; Coluccio, M. L.; Cojoc, G.; Accardo, A.; Liberale, C.; Zaccaria, R. P.; Perozziello, G.; Tirinato, L.; Toma, A.; Cuda, G.; Cingolani, R.; Di Fabrizio, E.Nature Photonics (2011), 5 (11), 682-687CODEN: NPAHBY; ISSN:1749-4885. (Nature Publishing Group)The detection of a few mols. in a highly dild. soln. is of paramount interest in fields including biomedicine, safety and eco-pollution in relation to rare and dangerous chems. Nanosensors based on plasmonics are promising devices in this regard, in that they combine the features of high sensitivity, label-free detection and miniaturization. However, plasmonic-based nanosensors, in common with general sensors with sensitive areas on the scale of nanometers, cannot be used directly to detect mols. dissolved in femto- or attomolar solns. They are diffusion-limited and their detection times become impractical at such concns. In this Article, the authors demonstrate, by combining super-hydrophobic artificial surfaces and nanoplasmonic structures, that few mols. can be localized and detected even at attomolar (10-18 mol l-1) concn. Also, the detection can be combined with fluorescence and Raman spectroscopy, such that the chem. signature of the mols. can be clearly detd.
- 99Chen, X.; Ma, R.; Li, J.; Hao, C.; Guo, W.; Luk, B. L.; Li, S. C.; Yao, S.; Wang, Z. Evaporation of Droplets on Superhydrophobic Surfaces: Surface Roughness and Small Droplet Size Effects. Phys. Rev. Lett. 2012, 109, 116101, DOI: 10.1103/PhysRevLett.109.116101Google Scholar99Evaporation of droplets on superhydrophobic surfaces: surface roughness and small droplet size effectsChen, Xuemei; Ma, Ruiyuan; Li, Jintao; Hao, Chonglei; Guo, Wei; Luk, B. L.; Li, Shuai Cheng; Yao, Shuhuai; Wang, ZuankaiPhysical Review Letters (2012), 109 (11), 116101/1-116101/6CODEN: PRLTAO; ISSN:0031-9007. (American Physical Society)Evapn. of a sessile droplet is a complex, nonequil. phenomenon. Although evapg. droplets upon superhydrophobic surfaces have been known to exhibit distinctive evapn. modes such as a const. contact line (CCL), a const. contact angle (CCA), or both, our fundamental understanding of the effects of surface roughness on the wetting transition remains elusive. We show that the onset time for the CCL-CCA transition and the crit. base size at the Cassie-Wenzel transition exhibit remarkable dependence on the surface roughness. Through global interfacial energy anal. we reveal that, when the size of the evapg. droplet becomes comparable to the surface roughness, the line tension at the triple line becomes important in the prediction of the crit. base size. Last, we show that both the CCL evapn. mode and the Cassie-Wenzel transition can be effectively inhibited by engineering a surface with hierarchical roughness.
- 100Yang, S.; Dai, X.; Stogin, B. B.; Wong, T.-S. Ultrasensitive Surface-Enhanced Raman Scattering Detection in Common Fluids. Proc. Natl. Acad. Sci. U. S. A. 2016, 113, 268– 273, DOI: 10.1073/pnas.1518980113Google Scholar100Ultrasensitive surface-enhanced Raman scattering detection in common fluidsYang, Shikuan; Dai, Xianming; Stogin, Birgitt Boschitsch; Wong, Tak-SingProceedings of the National Academy of Sciences of the United States of America (2016), 113 (2), 268-273CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)Detecting target analytes with high specificity and sensitivity in any fluid is of fundamental importance to anal. science and technol. Surface-enhanced Raman scattering (SERS) has proven to be capable of detecting single mols. with high specificity, but achieving single-mol. sensitivity in any highly dild. solns. remains a challenge. Here we demonstrate a universal platform that allows for the enrichment and delivery of analytes into the SERS-sensitive sites in both aq. and nonaq. fluids, and its subsequent quant. detection of Rhodamine 6G (R6G) down to ∼75 fM level (10-15 mol·L-1). Our platform, termed slippery liq.-infused porous surface-enhanced Raman scattering (SLIPSERS), is based on a slippery, omniphobic substrate that enables the complete concn. of analytes and SERS substrates (e.g., Au nanoparticles) within an evapg. liq. droplet. Combining our SLIPSERS platform with a SERS mapping technique, we have systematically quantified the probability, p(c), of detecting R6G mols. at concns. c ranging from 750 fM (p > 90%) down to 75 aM (10-18 mol·L-1) levels (p ≤ 1.4%). The ability to detect analytes down to attomolar level is the lowest limit of detection for any SERS-based detection reported thus far. We have shown that analytes present in liq., solid, or air phases can be extd. using a suitable liq. solvent and subsequently detected through SLIPSERS. Based on this platform, we have further demonstrated ultrasensitive detection of chem. and biol. mols. as well as environmental contaminants within a broad range of common fluids for potential applications related to anal. chem., mol. diagnostics, environmental monitoring, and national security.
- 101Wong, T.-S.; Kang, S. H.; Tang, S. K. Y.; Smythe, E. J.; Hatton, B. D.; Grinthal, A.; Aizenberg, J. Bioinspired Self-Repairing Slippery Surfaces with Pressure-Stable Omniphobicity. Nature 2011, 477, 443– 447, DOI: 10.1038/nature10447Google Scholar101Bioinspired self-repairing slippery surfaces with pressure-stable omniphobicityWong, Tak-Sing; Kang, Sung Hoon; Tang, Sindy K. Y.; Smythe, Elizabeth J.; Hatton, Benjamin D.; Grinthal, Alison; Aizenberg, JoannaNature (London, United Kingdom) (2011), 477 (7365), 443-447CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)Creating a robust synthetic surface that repels various liqs. would have broad technol. implications for areas ranging from biomedical devices and fuel transport to architecture but proved extremely challenging. Inspirations from natural nonwetting structures, particularly the leaves of the lotus, led to the development of liq.-repellent microtextured surfaces that rely on the formation of a stable air-liq. interface. Despite over a decade of intense research, these surfaces are, however, still plagued with problems that restrict their practical applications: limited oleophobicity with high contact angle hysteresis, failure under pressure and upon phys. damage, inability to self-heal and high prodn. cost. To address these challenges, here the authors report a strategy to create self-healing, slippery liq.-infused porous surface(s) (SLIPS) with exceptional liq.- and ice-repellency, pressure stability and enhanced optical transparency. The approach-inspired by Nepenthes pitcher plants-is conceptually different from the lotus effect, because the authors use nano/microstructured substrates to lock in place the infused lubricating fluid. The authors define the requirements for which the lubricant forms a stable, defect-free and inert slippery' interface. This surface outperforms its natural counterparts and state-of-the-art synthetic liq.-repellent surfaces in its capability to repel various simple and complex liqs. (water, hydrocarbons, crude oil and blood), maintain low contact angle hysteresis ( < 2.5°), quickly restore liq.-repellency after phys. damage (within 0.1-1 s), resist ice adhesion, and function at high pressures (up to ∼680 atm). These properties are insensitive to the precise geometry of the underlying substrate, making the approach applicable to various inexpensive, low-surface-energy structured materials (such as porous Teflon membrane). The authors envision that these slippery surfaces will be useful in fluid handling and transportation, optical sensing, medicine, and as self-cleaning and anti-fouling materials operating in extreme environments.
- 102Aldeanueva-Potel, P.; Faoucher, E.; Alvarez-Puebla, R. A.; Liz-Marzán, L. M.; Brust, M. Recyclable molecular trapping and SERS detection in silver-loaded agarose gels with dynamic hot spots. Anal. Chem. 2009, 81, 9233– 8, DOI: 10.1021/ac901333pGoogle Scholar102Recyclable Molecular Trapping and SERS Detection in Silver-Loaded Agarose Gels with Dynamic Hot SpotsAldeanueva-Potel, Paula; Faoucher, Erwan; Alvarez-Puebla, Ramon A.; Liz-Marzan, Luis M.; Brust, MathiasAnalytical Chemistry (Washington, DC, United States) (2009), 81 (22), 9233-9238CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)We describe the design and fabrication of composite agarose gels, highly loaded with silver nanoparticles. Because the gel can collapse upon drying and recover when rehydrated, it can be foreseen as an excellent mech. mol. trap that addnl. gives rise to dynamic hot spots as the network vol. decreases and the silver particles get close to each other, thereby generating the high electromagnetic fields that are needed for ultradetection. Addnl., as silver nanoparticles are phys. trapped inside the polymer network, analytes can be washed out by dialysis when immersed in a washing soln., so that recycling can be achieved. Finally, the use of SERS for ultradetection of dichlorodiphenyl-trichloroethane (DDT) is reported for the first time, demonstrating the ability of this novel nanocomposite material to reversibly sequester nonconventional SERS analytes.
- 103Troncoso-Afonso, L.; Vinnacombe-Willson, G. A.; García-Astrain, C.; Liz-Márzan, L. M. SERS in 3D cell models: a powerful tool in cancer research. Chem. Soc. Rev. 2024, 53, 5118– 5148, DOI: 10.1039/D3CS01049JGoogle ScholarThere is no corresponding record for this reference.
- 104Jimenez de Aberasturi, D.; Henriksen-Lacey, M.; Litti, L.; Langer, J.; Liz-Marzán, L. M. Using SERS Tags to Image the Three-Dimensional Structure of Complex Cell Models. Adv. Funct. Mater. 2020, 30, 1909655, DOI: 10.1002/adfm.201909655Google Scholar104Using SERS Tags to Image the Three-Dimensional Structure of Complex Cell ModelsJimenez de Aberasturi, Dorleta; Henriksen-Lacey, Malou; Litti, Lucio; Langer, Judith; Liz-Marzan, Luis M.Advanced Functional Materials (2020), 30 (14), 1909655CODEN: AFMDC6; ISSN:1616-301X. (Wiley-VCH Verlag GmbH & Co. KGaA)Methods to image complex 3D cell cultures are limited by issues such as fluorophore photobleaching and decompn., poor excitation light penetration, and lack of complementary techniques to verify the 3D structure. Although it remains insufficiently demonstrated, surface-enhanced Raman scattering (SERS) imaging is a promising tool for the characterization of biol. complex systems. To this aim, a controllable 3D cell culture model which spans nearly 1 cm2 in surface footprint is designed. This structure is composed of fibroblasts contg. SERS-encoded nanoparticles (i.e., SERS tags), arranged in an alternating layered structure. This "sandwich" type structure allows monitoring of the SERS signals in the z-axis and with mm dimensions in the xy-axis. Taking advantage of correlative microscopy techniques such as electron microscopy, it is possible to corroborate nanoparticle positioning and distances in z-depths of up to 150μm. This study reveals a proof-of-concept method for detailed 3D SERS imaging of a complex, dense 3D cell culture model.
- 105García-Astrain, C.; Lenzi, E.; Jimenez de Aberasturi, D.; Henriksen-Lacey, M.; Binelli, M. R.; Liz-Marzán, L. M. 3D-Printed Biocompatible Scaffolds with Built-In Nanoplasmonic Sensors. Adv. Funct. Mater. 2020, 30, 2005407, DOI: 10.1002/adfm.202005407Google Scholar1053D-Printed Biocompatible Scaffolds with Built-In Nanoplasmonic SensorsGarcia-Astrain, Clara; Lenzi, Elisa; Jimenez de Aberasturi, Dorleta; Henriksen-Lacey, Malou; Binelli, Marco R.; Liz-Marzan, Luis M.Advanced Functional Materials (2020), 30 (45), 2005407CODEN: AFMDC6; ISSN:1616-301X. (Wiley-VCH Verlag GmbH & Co. KGaA)3D printing strategies have acquired great relevance toward the design of 3D scaffolds with precise macroporous structures, for supported mammalian cell growth. Despite advances in 3D model designs, there is still a shortage of detection tools to precisely monitor in situ cell behavior in 3D, thereby allowing a better understanding of the progression of diseases or to test the efficacy of drugs in a more realistic microenvironment. Even if the no. of available inks has exponentially increased, they do not necessarily offer the required functionalities to be used as internal sensors. Herein the potential of surface-enhanced Raman scattering (SERS) spectroscopy for the detection of biorelevant analytes within a plasmonic hydrogel-based, 3D-printed scaffold is demonstrated. Such SERS-active scaffolds allow for the 3D detection of model mols., such as 4-mercaptobenzoic acid. Flexibility in the choice of plasmonic nanoparticles is demonstrated through the use of gold nanoparticles with different morphologies, gold nanorods showing the best balance between SERS enhancement and scaffold transparency. Detection of the biomarker adenosine is also demonstrated as a proof-of-concept toward the use of these plasmonic scaffolds for SERS sensing of cell-secreted mols. over extended periods of time.
- 106García-Astrain, C.; Henriksen-Lacey, M.; Lenzi, E.; Renero-Lecuna, C.; Langer, J.; Piñeiro, P.; Molina-Martínez, B.; Plou, J.; Jimenez de Aberasturi, D.; Liz-Marzán, L. M. A Scaffold-Assisted 3D Cancer Cell Model for Surface-Enhanced Raman Scattering-Based Real-Time Sensing and Imaging. ACS Nano 2024, 18, 11257– 11269, DOI: 10.1021/acsnano.4c00543Google ScholarThere is no corresponding record for this reference.
- 107González-Callejo, P.; García-Astrain, C.; Herrero-Ruiz, A.; Henriksen-Lacey, M.; Seras-Franzoso, J.; Abasolo, I.; Liz-Marzán, L. M. 3D Bioprinted Tumor-Stroma Models of Triple-Negative Breast Cancer Stem Cells for Preclinical Targeted Therapy Evaluation. ACS Appl. Mater. & Interfaces 2024, 16, 27151– 27163, DOI: 10.1021/acsami.4c04135Google ScholarThere is no corresponding record for this reference.
- 108Quintanilla, M.; Henriksen-Lacey, M.; Renero-Lecuna, C.; Liz-Marzán, L. M. Challenges for optical nanothermometry in biological environments. Chem. Soc. Rev. 2022, 51, 4223– 4242, DOI: 10.1039/D2CS00069EGoogle Scholar108Challenges for optical nanothermometry in biological environmentsQuintanilla, Marta; Henriksen-Lacey, Malou; Renero-Lecuna, Carlos; Liz-Marzan, Luis M.Chemical Society Reviews (2022), 51 (11), 4223-4242CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)Temp. monitoring is useful in medical diagnosis, and essential during hyperthermia treatments to avoid undesired cytotoxic effects. Aiming to control heating doses, different temp. monitoring strategies have been developed, largely based on luminescent materials, a.k.a. nanothermometers. However, for such nanothermometers to work, both excitation and emission light beams must travel through tissue, making its optical properties a relevant aspect to be considered during the measurements. In complex tissues, heterogeneity, and real-time alterations as a result of therapeutic treatment may have an effect on light-tissue interaction, hindering accuracy in the thermal reading. In this Tutorial Review we discuss various methods in which nanothermometers can be used for temp. sensing within heterogeneous environments. We discuss recent developments in optical (nano)thermometry, focusing on the incorporation of luminescent nanoparticles into complex in vitro and in vivo models. Methods formulated to avoid thermal misreading are also discussed, considering their resp. advantages and drawbacks.
- 109Lenzi, E.; Jimenez de Aberasturi, D.; Liz-Marzán, L. M. Surface-Enhanced Raman Scattering Tags for Three-Dimensional Bioimaging and Biomarker Detection. ACS Sens. 2019, 4, 1126– 1137, DOI: 10.1021/acssensors.9b00321Google Scholar109Surface-Enhanced Raman Scattering Tags for Three-Dimensional Bioimaging and Biomarker DetectionLenzi, Elisa; Jimenez de Aberasturi, Dorleta; Liz-Marzan, Luis M.ACS Sensors (2019), 4 (5), 1126-1137CODEN: ASCEFJ; ISSN:2379-3694. (American Chemical Society)A review. The authors have recently witnessed a major improvement in the quality of nanoparticles encoded with Raman-active mols. (SERS tags). Such a progress relied mainly on a major improvement of fabrication methods for building-blocks, resulting in widespread application of this powerful tool in various fields, with the potential to replace commonly used techniques, such as those based on fluorescence. The authors present hereby a brief perspective on SERS tags, regarding their compn., morphol. and structure, and describe the own selection from the current state-of-the-art. The authors then focus on the main bioimaging applications of SERS tags, showing a gradual evolution from two-dimensional studies to three-dimensional anal. Recent improvements in sensitivity and multiplexing ability have enabled great advancements toward in vivo applications, e.g. highlighting tumor boundaries to guide surgery. In addn., the high level of biomol. sensitivity reached by SERS tags, promises an expansion toward biomarker detection in cases for which traditional methods offer limited reliability, as a consequence of the frequently low analyte concns.
- 110Vázquez-Aristizabal, P.; Henriksen-Lacey, M.; García-Astrain, C.; Jimenez de Aberasturi, D.; Langer, J.; Epelde, C.; Litti, L.; Liz-Marzán, L. M.; Izeta, A. Biofabrication and Monitoring of a 3D Printed Skin Model for Melanoma. Adv. Healthc. Mater. 2024, 13, 2401136, DOI: 10.1002/adhm.202401136Google ScholarThere is no corresponding record for this reference.
- 111Jimenez de Aberasturi, D.; Serrano-Montes, A. B.; Langer, J.; Henriksen-Lacey, M.; Parak, W. J.; Liz-Marzán, L. M. SERS-Encoded Gold Nanostars for Multiplexed Cell Discrimination. Chem. Mater. 2016, 28, 6779– 6810, DOI: 10.1021/acs.chemmater.6b03349Google Scholar111Surface Enhanced Raman Scattering Encoded Gold Nanostars for Multiplexed Cell DiscriminationJimenez de Aberasturi, Dorleta; Serrano-Montes, Ana B.; Langer, Judith; Henriksen-Lacey, Malou; Parak, Wolfgang J.; Liz-Marzan, Luis M.Chemistry of Materials (2016), 28 (18), 6779-6790CODEN: CMATEX; ISSN:0897-4756. (American Chemical Society)Labeled nanoparticles have attracted much interest toward applications in bioimaging and diagnostics. In particular, surface enhanced Raman scattering (SERS) nanotags have been demonstrated to be excellent candidates for multiplexed imaging and biol. detection. The authors propose an alternative, effective method to easily prep. gold nanostars exhibiting plasmon bands in the near IR range, encoded with Raman reporter mols., concomitantly acting as capping agents which are then protected with an amphiphilic polymer. The resulting nanotags are non-cytotoxic and display long-term stability against aggregation and reporter leakage, while showing reproducible SERS signals suitable for multiplexing. These tags were used to distinguish five different types of breast cancer cells by imaging of a quintuple cell coculture. Time-lapse SERS imaging of the coculture was addnl. performed, demonstrating the applicability of these nanotags for cell tracing over time scales >24 h.
- 112Zhuo, X.; Henriksen-Lacey, M.; Jimenez de Aberasturi, D.; Sánchez-Iglesias, A.; Liz-Marzán, L. M. Shielded Silver Nanorods for Bioapplications. Chem. Mater. 2020, 32, 5879– 5889, DOI: 10.1021/acs.chemmater.0c01995Google Scholar112Shielded Silver Nanorods for BioapplicationsZhuo, Xiaolu; Henriksen-Lacey, Malou; Jimenez de Aberasturi, Dorleta; Sanchez-Iglesias, Ana; Liz-Marzan, Luis M.Chemistry of Materials (2020), 32 (13), 5879-5889CODEN: CMATEX; ISSN:0897-4756. (American Chemical Society)Silver is arguably the best plasmonic material in terms of optical performance. However, wide application of Ag and Ag-contg. nanoparticles is usually hindered by two major drawbacks, namely, chem. degrdn. and cytotoxicity. The authors report herein a synthetic method for highly monodisperse polymer-coated Ag nanorods, which are thereby protected against external stimuli (oxidn., light, heat) and are noncytotoxic to various cell lines. The monodispersity of Ag nanorods endows them with narrow plasmon bands, which are tunable into the near-IR biol. transparency window, thus facilitating application in bioanal. and therapeutic techniques. The authors demonstrate intracellular surface-enhanced Raman scattering (SERS) imaging using Ag nanorods encoded with five different Raman reporter mols. Encoded Ag nanorods display long-term stability in terms of size, shape, optical response, and SERS signal. The authors' results help eliminate concerns of instability and cytotoxicity in the application of Ag-contg. nanoparticles with enhanced optical response, toward the development of bioapplications.
- 113Plou, J.; Molina-Martínez, B.; García-Astrain, C.; Langer, J.; García, I.; Ercilla, A.; Perumal, G.; Carracedo, A.; Liz-Marzán, L. M. Nanocomposite Scaffolds for Monitoring of Drug Diffusion in Three-Dimensional Cell Environments by Surface-Enhanced Raman Spectroscopy. Nano Lett. 2021, 21, 8785– 8793, DOI: 10.1021/acs.nanolett.1c03070Google Scholar113Nanocomposite Scaffolds for Monitoring of Drug Diffusion in Three-Dimensional Cell Environments by Surface-Enhanced Raman SpectroscopyPlou, Javier; Molina-Martinez, Beatriz; Garcia-Astrain, Clara; Langer, Judith; Garcia, Isabel; Ercilla, Amaia; Perumal, Govindaraj; Carracedo, Arkaitz; Liz-Marzan, Luis M.Nano Letters (2021), 21 (20), 8785-8793CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)Monitoring dynamic processes in complex cellular environments requires the integration of uniformly distributed detectors within such three-dimensional (3D) networks, to an extent that the sensor could provide real-time information on nearby perturbations in a non-invasive manner. In this context, the development of 3D-printed structures that can function as both sensors and cell culture platforms emerges as a promising strategy, not only for mimicking a specific cell niche but also toward identifying its characteristic physicochem. conditions, such as concn. gradients. We present herein a 3D cancer model that incorporates a hydrogel-based scaffold contg. gold nanorods. In addn. to sustaining cell growth, the printed nanocomposite inks display the ability to uncover drug diffusion profiles by surface-enhanced Raman scattering, with high spatiotemporal resoln. We addnl. demonstrate that the acquired information could pave the way to designing novel strategies for drug discovery in cancer therapy, through correlation of drug diffusion with cell death.
- 114Aizarna-Lopetegui, U.; García-Astrain, C.; Renero-Lecuna, C.; González-Callejo, P.; Villaluenga, I.; del Pozo, M. A.; Sánchez-Álvarez, M.; Henriksen-Lacey, M.; Jimenez de Aberasturi, D. Remodeling arteries: studying the mechanical properties of 3D-bioprinted hybrid photoresponsive materials. J. Mater. Chem. B 2023, 11, 9431– 9442, DOI: 10.1039/D3TB01480KGoogle ScholarThere is no corresponding record for this reference.
- 115Zhu, K.; Shin, S. R.; van Kempen, T.; Li, Y. C.; Ponraj, V.; Nasajpour, A.; Mandla, S.; Hu, N.; Liu, X.; Leijten, J.; Lin, Y. D.; Hussain, M. A.; Zhang, Y. S.; Tamayol, A.; Khademhosseini, A. Gold Nanocomposite Bioink for Printing 3D Cardiac Constructs. Adv. Funct Mater. 2017, 27, 1605352, DOI: 10.1002/adfm.201605352Google ScholarThere is no corresponding record for this reference.
- 116Alvarez-Puebla, R. A.; Liz-Marzán, L. M. SERS-Based Diagnosis and Biodetection. Small 2010, 6, 604– 610, DOI: 10.1002/smll.200901820Google Scholar116SERS-Based Diagnosis and BiodetectionAlvarez-Puebla, Ramon A.; Liz-Marzan, Luis M.Small (2010), 6 (5), 604-610CODEN: SMALBC; ISSN:1613-6810. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. Surface-enhanced Raman scattering (SERS) spectroscopy is one of the most powerful anal. techniques for identification of mol. species, with the potential to reach single-mol. detection under ambient conditions. This concept article presents a brief introduction and discussion of both recent advances and limitations of SERS in the context of diagnosis and biodetection, ranging from direct sensing to the use of encoded nanoparticles, in particular focusing on ultradetection of relevant bioanalytes, rapid diagnosis of diseases, marking of organelles within individual cells, and non-invasive tagging of anomalous tissues in living animals.
- 117Álvarez-Puebla, R. A.; Liz-Marzán, L. M. Environmental applications of plasmon assisted Raman scattering. Energy Environ. Sci. 2010, 3, 1011– 1017, DOI: 10.1039/c002437fGoogle Scholar117Environmental applications of plasmon assisted Raman scatteringAlvarez-Puebla, R. A.; Liz-Marzan, L. M.Energy & Environmental Science (2010), 3 (8), 1011-1017CODEN: EESNBY; ISSN:1754-5706. (Royal Society of Chemistry)We present in this review article an overview of the capabilities of surface enhanced Raman scattering (SERS) spectroscopy as a technique for applications related to environmental anal. and monitoring, ranging from the structural characterization of soils, through ultrasensitive detection of pollutants and heavy metal ions, to the anal. of plants, tissues and microorganisms, with a crit. approach in which the drawbacks and difficulties assocd. to the various exptl. configurations and enhancing substrates are introduced, as well as perspectives in the different fields.
- 118Alvarez-Puebla, R. A.; Liz-Marzán, L. M. Traps and cages for universal SERS detection. Chem. Soc. Rev. 2012, 41, 43– 51, DOI: 10.1039/C1CS15155JGoogle Scholar118Traps and cages for universal SERS detectionAlvarez-Puebla, Ramon A.; Liz-Marzan, Luis M.Chemical Society Reviews (2012), 41 (1), 43-51CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)A review. In this tutorial review, we provide an overview of the recent research toward surface functionalization of plasmonic nanoparticles for the generation of advanced optical sensors that make possible the anal. of various moieties by means of surface enhanced Raman scattering (SERS). Such moieties include at. ions, low affinity target mols., inorg. anions, biometabolites, pathogen markers and/or other analytes of interest even under very demanding circumstances such as those related to real life samples. We expect this review to be of interest to researchers in a broad diversity of fields that can take advantage of the unprecedented sensitivity of this type of mol. spectroscopy, in a wide variety of anal. and bioanal. problems.
- 119Fernández-López, C.; Mateo-Mateo, C.; Álvarez-Puebla, R. A.; Pérez-Juste, J.; Pastoriza-Santos, I.; Liz-Marzán, L. M. Highly Controlled Silica Coating of PEG-Capped Metal Nanoparticles and Preparation of SERS-Encoded Particles. Langmuir 2009, 25, 13894– 13899, DOI: 10.1021/la9016454Google Scholar119Highly Controlled Silica Coating of PEG-Capped Metal Nanoparticles and Preparation of SERS-Encoded ParticlesFernandez-Lopez, Cristina; Mateo-Mateo, Cintia; Alvarez-Puebla, Ramon A.; Perez-Juste, Jorge; Pastoriza-Santos, Isabel; Liz-Marzan, Luis M.Langmuir (2009), 25 (24), 13894-13899CODEN: LANGD5; ISSN:0743-7463. (American Chemical Society)Thiol-modified poly(ethylene glycol) (mPEG-SH) has been used to replace std. capping agents from the surfaces of gold nanoparticles with different sizes and shapes. Upon PEG stabilization, the nanoparticles can be transferred into ethanol, where silica can be directly grown on the particle surfaces through the std. Stober process. The obtained silica shells are uniform and homogeneous, and the method allows a high degree of control over shell thickness for any particle size and shape. Addnl., Raman-active mols. can be readily incorporated within the composite nanoparticles during silica growth so that SERS/SERRS-encoded nanoparticles can be fabricated contg. a variety of tags, thereby envisaging multiplexing capability.
- 120Alvarez-Puebla, R.; Liz-Marzán, L. M.; García de Abajo, F. J. Light Concentration at the Nanometer Scale. J. Phys. Chem. Lett. 2010, 1, 2428– 2434, DOI: 10.1021/jz100820mGoogle Scholar120Light Concentration at the Nanometer ScaleAlvarez-Puebla, Ramon; Liz-Marzan, Luis M.; Garcia de Abajo, F. JavierJournal of Physical Chemistry Letters (2010), 1 (16), 2428-2434CODEN: JPCLCD; ISSN:1948-7185. (American Chemical Society)Visible and near-IR optical excitations are common currency in the biol. world, and consequently, they are routinely used to study microscopic phenomena taking place in living organisms and their environment. However, the wavelength of light within that energy region is above hundreds of nanometers, thus averting the possibility of direct nanometer-scale resoln. The authors show in this perspective that narrow gaps between metals and sharp tips in colloidal Au particles constitute excellent light confiners that permit solving this problem, and in particular, they lead to record levels of surface-enhanced Raman scattering. The authors' results are framed in the context of a historical quest toward achieving optical focusing in the near field, and the authors offer a tutorial explanation of why evanescent waves such as plasmons are needed for deep-subwavelength focusing. These results provide the required elements of intuition to understand light concn. at the nanometer scale and to design optimized systems for application in ultrasensitive optical analyses and nonlinear photonics.
- 121Becerril-Castro, I. B.; Calderon, I.; Pazos-Perez, N.; Guerrini, L.; Schulz, F.; Feliu, N.; Chakraborty, I.; Giannini, V.; Parak, W. J.; Alvarez-Puebla, R. A. Gold nanostars: Synthesis, optical and SERS analytical properties. Analysis & Sensing 2022, 2, e202200005, DOI: 10.1002/anse.202200022Google ScholarThere is no corresponding record for this reference.
- 122Blanco-Formoso, M.; Sousa-Castillo, A.; Xiao, X.; Mariño-Lopez, A.; Turino, M.; Pazos-Perez, N.; Giannini, V.; Correa-Duarte, M. A.; Alvarez-Puebla, R. A. Boosting the analytical properties of gold nanostars by single particle confinement into yolk porous silica shells. Nanoscale 2019, 11, 21872– 21879, DOI: 10.1039/C9NR07889DGoogle Scholar122Boosting the analytical properties of gold nanostars by single particle confinement into yolk porous silica shellsBlanco-Formoso, Maria; Sousa-Castillo, Ana; Xiao, Xiaofei; Marino-Lopez, Andrea; Turino, Mariacristina; Pazos-Perez, Nicolas; Giannini, Vincenzo; Correa-Duarte, Miguel A.; Alvarez-Puebla, Ramon A.Nanoscale (2019), 11 (45), 21872-21879CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)Herein we illustrate an effective protocol to boost the optical enhancing properties of gold nanostars. By coating single nanostars with a mesoporous silica layer of the appropriate size (yolk capsules), to localize them under optical microscopy, it is possible to enumerate single particles and design SERS quant. methods with minute amts. of metallic particles.
- 123Mariño-Lopez, A.; Sousa-Castillo, A.; Blanco-Formoso, M.; Furini, L. N.; Rodríguez-Lorenzo, L.; Pazos-Perez, N.; Guerrini, L.; Pérez-Lorenzo, M.; Correa-Duarte, M. A.; Alvarez-Puebla, R. A. Microporous Plasmonic Capsules as Stable Molecular Sieves for Direct SERS Quantification of Small Pollutants in Natural Waters. ChemNanoMat 2019, 5, 46– 50, DOI: 10.1002/cnma.201800355Google Scholar123Microporous Plasmonic Capsules as Stable Molecular Sieves for Direct SERS Quantification of Small Pollutants in Natural WatersMarino-Lopez, Andrea; Sousa-Castillo, Ana; Blanco-Formoso, Maria; Furini, Leonardo N.; Rodriguez-Lorenzo, Laura; Pazos-Perez, Nicolas; Guerrini, Luca; Perez-Lorenzo, Moises; Correa-Duarte, Miguel A.; Alvarez-Puebla, Ramon A.ChemNanoMat (2019), 5 (1), 46-50CODEN: CHEMSB; ISSN:2199-692X. (Wiley-VCH Verlag GmbH & Co. KGaA)Fast and versatile optical SERS methods represent a major advance in chem. anal. of environmental samples such as water. To date, however, these ultrasensitive methods are hindered by two key drawbacks: (i) colloidal stability and (ii) chem. diversity, both arising from the compositional complexity of natural samples. Here, we present an engineered material that, due to its unique microporous structure, imparts colloidal stability and provides selectivity while confining a densely populated film of gold nanoparticles optimized for the generation of large electromagnetic fields. The material is tested against natural water for the ultraquantification of dichlorodiphenyl-trichloroethane (DDT), a ubiquitous environmental pollutant.
- 124Sanles-Sobrido, M.; Exner, W.; Rodriguez-Lorenzo, L.; Rodriguez-Gonzalez, B.; Correa-Duarte, M. A.; Alvarez-Puebla, R. A.; Liz-Marzan, L. M. Design of SERS-encoded, submicron, hollow particles through confined growth of encapsulated metal nanoparticles. J. Am. Chem. Soc. 2009, 131, 2699– 2705, DOI: 10.1021/ja8088444Google Scholar124Design of SERS-Encoded, Submicron, Hollow Particles Through Confined Growth of Encapsulated Metal NanoparticlesSanles-Sobrido, Marcos; Exner, Wibke; Rodriguez-Lorenzo, Laura; Rodriguez-Gonzalez, Benito; Correa-Duarte, Miguel A.; Alvarez-Puebla, Ramon A.; Liz-Marzan, Luis M.Journal of the American Chemical Society (2009), 131 (7), 2699-2705CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)The synthetic architectures of complex inorg. nanostructures, including multifunctional hollow capsules, are expected to play key roles in many different applications, such as drug delivery, photonic crystals, nanoreactors, and sensing. Implementation of novel strategies for the fabrication of such materials is needed because of the infancy of this knowledge, which still limits progress in certain areas. Herein the authors report a straightforward synthetic approach for the development of multifunctional submicron reactors comprising catalytic gold nanoparticles (2-3 nm) confined inside hollow silica capsules. Addnl., the confined growth of encapsulated metal nanoparticles was carried out to evidence the usefulness and functionality of these reactors in catalytic applications and as an approach for the development of novel complex nanostructures. Their potential and multifunctionality were pointed out by fabrication of SERS-encoded submicrometer particles with shape and size uniformity for use in antigen biosensing; this was accomplished via codification of gold nanoparticle islands grown onto their inner surfaces.
- 125Riveragil, P.; Vazquez-Vazquez, C.; Giannini, V.; Callao, M. P.; Parak, W. J.; Correa-Duarte, M. A.; Alvarez-Puebla, R. A. Plasmonic nanoprobes for real-time optical monitoring of nitric oxide inside living cells. Angewandte Chemie - International Edition 2013, 52, 13694– 13698, DOI: 10.1002/anie.201306390Google ScholarThere is no corresponding record for this reference.
- 126Vázquez-Vázquez, C.; Vaz, B.; Giannini, V.; Pérez-Lorenzo, M.; Alvarez-Puebla, R. A.; Correa-Duarte, M. A. Nanoreactors for simultaneous remote thermal activation and optical monitoring of chemical reactions. J. Am. Chem. Soc. 2013, 135, 13616– 13619, DOI: 10.1021/ja4051873Google Scholar126Nanoreactors for Simultaneous Remote Thermal Activation and Optical Monitoring of Chemical ReactionsVazquez-Vazquez, Carmen; Vaz, Belen; Giannini, Vincenzo; Perez-Lorenzo, Moises; Alvarez-Puebla, Ramon A.; Correa-Duarte, Miguel A.Journal of the American Chemical Society (2013), 135 (37), 13616-13619CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)We report herein the design of plasmonic hollow nanoreactors capable of concg. light at the nanometer scale for the simultaneous performance and optical monitoring of thermally activated reactions. These reactors feature the encapsulation of plasmonic nanoparticles on the inner walls of a mesoporous silica capsule. A Diels-Alder cycloaddn. reaction was carried out in the inner cavities of these nanoreactors to evidence their efficacy. Thus, it is demonstrated that reactions can be accomplished in a confined vol. without alteration of the temp. of the bulk solvent while allowing real-time monitoring of the reaction progress.
- 127Zorlu, T.; Correa-Duarte, M. A.; Alvarez-Puebla, R. A. Composite nanoparticle-metal-organic frameworks for SERS sensing. J. Chem. Phys. 2023, 158, 171001, DOI: 10.1063/5.0144695Google ScholarThere is no corresponding record for this reference.
- 128Zorlu, T.; Becerril-Castro, I. B.; Puertolas, B.; Giannini, V.; Correa-Duarte, M. A.; Alvarez-Puebla, R. A. Yolk-Shell Nanostars@Metal Organic Frameworks as Molecular Sieves for Optical Sensing and Catalysis. Angew. Chem., Int. Ed. Engl. 2023, 62, e202305299, DOI: 10.1002/anie.202305299Google ScholarThere is no corresponding record for this reference.
- 129Men, D.; Feng, S.; Liu, G.; Hang, L.; Zhang, T. A Sensitive “Optical Nose” for Detection of Volatile Organic Molecules Based on Au@ MOFs Nanoparticle Arrays through Surface-Enhanced Raman Scattering. Particle & Particle Systems Characterization 2020, 37, 1900452, DOI: 10.1002/ppsc.201900452Google ScholarThere is no corresponding record for this reference.
- 130Cai, Y.; Wu, Y.; Xuan, T.; Guo, X.; Wen, Y.; Yang, H. Core–shell Au@ metal–organic frameworks for promoting Raman detection sensitivity of methenamine. ACS Appl. Mater. Interfaces 2018, 10, 15412– 15417, DOI: 10.1021/acsami.8b01765Google Scholar130Core-Shell Au@Metal-Organic Frameworks for Promoting Raman Detection Sensitivity of MethenamineCai, Yanzheng; Wu, Yiping; Xuan, Tong; Guo, Xiaoyu; Wen, Ying; Yang, HaifengACS Applied Materials & Interfaces (2018), 10 (18), 15412-15417CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Abuse of methenamine in foodstuff is harmful to the health of people. Routine methods recommended by the national std. are indirect assays with complicated pretreatment of samples or less sensitivity. Core-shell Au nanoparticles@inositol hexaphosphate@MIL-101(Fe) nanoparticles, designated as Au@MIL-101, are successfully synthesized by layer-by-layer assembly. Metal-org. framework (MOF; MIL-101)-modified AuNPs could narrow the distance between neighboring Au@MIL-101, which increases the amt. of hot spots and contributes excellent enhancement of Raman scattering. Certain target mols. could access the proximity to the hot spots by the strong interaction capability of MOF with -COOH groups. Taking the syngeneic effect of hot spots and chem. enhancement via specific binding, Au@MIL-101-based Raman protocol with huge sensitivity is developed to achieve direct detection of methenamine. It has good linearity of dynamic concn. from 3.16 × 10-6 to 1.0 × 10-8 M with correlation coeff. (R2) of 0.9908. The limit of detection reaches 5.0 × 10-10 M. As a practical application, such an Au@MIL-101-based Raman protocol could be used for the direct detn. of trace methenamine in vermicelli, which meets the requirements of the national std.
- 131Shang, W.; Zeng, C.; Du, Y.; Hui, H.; Liang, X.; Chi, C.; Wang, K.; Wang, Z.; Tian, J. Core-shell gold nanorod@ metal-organic framework nanoprobes for multimodality diagnosis of glioma. Advanced Materials (Deerfield Beach, Fla.) 2017, 29, na, DOI: 10.1002/adma.201604381Google ScholarThere is no corresponding record for this reference.
- 132Xie, X.; Zhang, Y.; Zhang, L.; Zheng, J.; Huang, Y.; Fa, H. Plasmon-Driven Interfacial Catalytic Reactions in Plasmonic MOF Nanoparticles. Anal. Chem. 2021, 93, 13219– 13225, DOI: 10.1021/acs.analchem.1c02272Google Scholar132Plasmon-Driven Interfacial Catalytic Reactions in Plasmonic MOF NanoparticlesXie, Xin; Zhang, Yaoyao; Zhang, Lingjun; Zheng, Jiangen; Huang, Yingzhou; Fa, HuanbaoAnalytical Chemistry (Washington, DC, United States) (2021), 93 (39), 13219-13225CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Benefiting from the noble metal nanoparticle core and org. porous nanoshell, plasmonic metal-org. frameworks (MOFs) become a nanostructure with great enhancement of the electromagnetic field and a high d. of reaction sites, which has fantastic optical properties in surface plasmon-related fields. In this work, the plasmon-driven interfacial catalytic reactions involving p-aminothiophenol to 4,4'-dimercaptoazobenzene (trans-DMAB) in both the liq. and gaseous phases are studied in plasmonic MOF nanoparticles, which consist of a Ag nanoparticle core and an org. shell (ZIF-8). The surface-enhanced Raman spectroscopy (SERS) spectra recorded at the plasmonic MOF in an aq. environment demonstrate that the reversible plasmon-driven interfacial catalytic reactions could be modulated by a reductant (NaBH4) or oxidant (H2O2). Also, the situ SERS spectra also point out that plasmonic MOF (AgNP@ZIF-8) nanoparticles exhibit much better catalytic performance in the H2O2 soln. compared to pure Ag nanoparticles for the anti-oxidn. caused by the MOF shell. It is surprising that although there is greater SERS enhancement obtained at pure Ag nanoparticles, the plasmon-driven interfacial catalytic reactions only occur at plasmonic AgNP@ZIF-8 nanoparticles in the gaseous phase. This interesting phenomenon is further confirmed and analyzed by simulated electromagnetic field distributions, which could be understood by the effective capture of gaseous mols. by the org. porous nanoshell. Our work not only explores the plasmonic MOF nanoparticles with unique optical properties but also strengthens the understanding of plasmon-driven interfacial catalytic reactions.
- 133Carrillo-Carrión, C.; Martínez, R.; Navarro Poupard, M. F.; Pelaz, B.; Polo, E.; Arenas-Vivo, A.; Olgiati, A.; Taboada, P.; Soliman, M. G.; Catalán, Ú.; Fernández-Castillejo, S.; Solà, R.; Parak, W. J.; Horcajada, P.; Alvarez-Puebla, R. A.; del Pino, P. Aqueous Stable Gold Nanostar/ZIF-8 Nanocomposites for Light-Triggered Release of Active Cargo Inside Living Cells. Angewandte Chemie - International Edition 2019, 58, 7078– 7082, DOI: 10.1002/anie.201902817Google ScholarThere is no corresponding record for this reference.
- 134Zorlu, T.; Puértolas, B.; Becerril-Castro, I. B.; Guerrini, L.; Giannini, V.; Correa-Duarte, M. A.; Alvarez-Puebla, R. A. Optical Quantification of Metal Ions Using Plasmonic Nanostructured Microbeads Coated with Metal-Organic Frameworks and Ion-Selective Dyes. ACS Nanoscience Au 2023, 3, 222– 229, DOI: 10.1021/acsnanoscienceau.2c00063Google ScholarThere is no corresponding record for this reference.
- 135Zorlu, T.; Becerril-Castro, I. B.; Sousa-Castillo, A.; Puértolas, B.; Besteiro, L. V.; Wang, Z.; Govorov, A.; Correa-Duarte, M. A.; Alvarez-Puebla, R. A. Metal–Organic Frameworks Photocatalyst Through Plasmon-Induced Hot-Electrons. Adv. Funct. Mater. 2024, 34, 2410352, DOI: 10.1002/adfm.202410352Google ScholarThere is no corresponding record for this reference.
- 136Huang, C.; Li, A.; Chen, X.; Wang, T. Understanding the Role of Metal–Organic Frameworks in Surface-Enhanced Raman Scattering Application. Small 2020, 16, 2004802, DOI: 10.1002/smll.202004802Google Scholar136Understanding the Role of Metal-Organic Frameworks in Surface-Enhanced Raman Scattering ApplicationHuang, Chuanhui; Li, Ailin; Chen, Xiangyu; Wang, TieSmall (2020), 16 (43), 2004802CODEN: SMALBC; ISSN:1613-6810. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. Metal-org. frameworks (MOFs), built from org. linkers and metal ions/clusters, have emerged as highly promising materials for wide applications. Combining highly porous cryst. MOFs with the surface-enhanced Raman scattering (SERS) technique can achieve unprecedented advantages of high selectivity, high sensitivity, and expedience in anal. and detection. In this crit. review, the aim is to present a comprehensive review of recent advances in understanding of the roles of MOFs in MOF-SERS systems, particularly their structure-to-property correlation. Key examples are selected from representative literature to illustrate crit. concepts and the MOF-based property-dependent applications are particularly emphasized. The barriers, future trends, and prospects for further advances in MOF-SERS platforms are discussed.
- 137Kalaj, M.; Cohen, S. M. Postsynthetic modification: an enabling technology for the advancement of metal–organic frameworks. ACS Central Science 2020, 6, 1046– 1057, DOI: 10.1021/acscentsci.0c00690Google Scholar137Postsynthetic Modification: An Enabling Technology for the Advancement of Metal-Organic FrameworksKalaj, Mark; Cohen, Seth M.ACS Central Science (2020), 6 (7), 1046-1057CODEN: ACSCII; ISSN:2374-7951. (American Chemical Society)A review. Metal-org. frameworks (MOFs) are a class of porous materials with immense chem. tunability derived from their org. and inorg. building blocks. Presynthetic approaches were used to construct tailor-made MOFs, but with a rather restricted functional group scope limited by the typical MOF solvothermal synthesis conditions. Postsynthetic modification (PSM) of MOFs has matured into an alternative strategy to broaden the functional group scope of MOFs. PSM has many incarnations, but 2 main avenues include (1) covalent PSM, in which the org. linkers of the MOF are modified with a reagent resulting in new functional groups, and (2) coordinative PSM, where org. mols. contg. metal ligating groups are introduced onto the inorg. secondary building units (SBUs) of the MOF. These methods have evolved from simple efforts to modifying MOFs to demonstrate proof-of-concept, to becoming key synthetic tools for advancing MOFs for a range of emerging applications, including selective gas sorption, catalysis, and drug delivery. Also, both covalent and coordinative PSM were used to create hierarchal MOFs, MOF-based porous liqs., and other unusual MOF materials. This Outlook highlights recent reports that have extended the scope of PSM in MOFs, some seminal reports that have contributed to the advancement of PSM in MOFs, and view on future directions of the field. The authors highlight recent advances in covalent and coordinative postsynthetic modification of metal-org. frameworks (MOFs) and how these methods have advanced the use of MOFs as functional materials.
- 138Dolgopolova, E. A.; Brandt, A. J.; Ejegbavwo, O. A.; Duke, A. S.; Maddumapatabandi, T. D.; Galhenage, R. P.; Larson, B. W.; Reid, O. G.; Ammal, S. C.; Heyden, A.; Chandrashekhar, M. V. S.; Stavila, V.; Chen, D.; Shustova, N. B. Electronic Properties of Bimetallic Metal–Organic Frameworks (MOFs): Tailoring the Density of Electronic States Through MOF Modularity. J. Am. Chem. Soc. 2017, 139, 5201– 5209, DOI: 10.1021/jacs.7b01125Google Scholar138Electronic Properties of Bimetallic Metal-Organic Frameworks (MOFs): Tailoring the Density of Electronic States through MOF ModularityDolgopolova, Ekaterina A.; Brandt, Amy J.; Ejegbavwo, Otega A.; Duke, Audrey S.; Maddumapatabandi, Thathsara D.; Galhenage, Randima P.; Larson, Bryon W.; Reid, Obadiah G.; Ammal, Salai C.; Heyden, Andreas; Chandrashekhar, Mvs; Stavila, Vitalie; Chen, Donna A.; Shustova, Natalia B.Journal of the American Chemical Society (2017), 139 (14), 5201-5209CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)The development of porous well-defined hybrid materials (e.g., metal-org. frameworks or MOFs) will add a new dimension to a wide no. of applications ranging from supercapacitors and electrodes to smart membranes and thermoelecs. From this perspective, the understanding and tailoring of the electronic properties of MOFs are key fundamental challenges that could unlock the full potential of these materials. The authors focused on the fundamental insights responsible for the electronic properties of three distinct classes of bimetallic systems, Mx-yM'y-MOFs, MxM'y-MOFs, and Mx(ligand-M'y)-MOFs, in which the 2nd metal (M') incorporation occurs through (i) metal (M) replacement in the framework nodes (type I), (ii) metal node extension (type II), and (iii) metal coordination to the org. ligand (type III), resp. The authors employed microwave cond., XPS, diffuse reflectance spectroscopy, powder x-ray diffraction, inductively coupled plasma at. emission spectroscopy, pressed-pellet cond., and theor. modeling to shed light on the key factors responsible for the tunability of MOF electronic structures. Exptl. prescreening of MOFs was performed based on changes in the d. of electronic states near the Fermi edge, which was used as a starting point for further selection of suitable MOFs. As a result, the tailoring of MOF electronic properties could be performed as a function of metal node engineering, framework topol., and/or the presence of unsatd. metal sites while preserving framework porosity and structural integrity. These studies unveil the possible pathways for transforming the electronic properties of MOFs from insulating to semiconducting, as well as provide a blueprint for the development of hybrid porous materials with desirable electronic structures.
- 139Guselnikova, O.; Postnikov, P.; Kolska, Z.; Zaruba, K.; Kohout, M.; Elashnikov, R.; Svorcik, V.; Lyutakov, O. Homochiral metal-organic frameworks functionalized SERS substrate for atto-molar enantio-selective detection. Applied Materials Today 2020, 20, 100666, DOI: 10.1016/j.apmt.2020.100666Google ScholarThere is no corresponding record for this reference.
- 140Arabi, M.; Ostovan, A.; Wang, Y.; Mei, R.; Fu, L.; Li, J.; Wang, X.; Chen, L. Chiral molecular imprinting-based SERS detection strategy for absolute enantiomeric discrimination. Nat. Commun. 2022, 13, 5757, DOI: 10.1038/s41467-022-33448-wGoogle Scholar140Chiral molecular imprinting-based SERS detection strategy for absolute enantiomeric discriminationArabi, Maryam; Ostovan, Abbas; Wang, Yunqing; Mei, Rongchao; Fu, Longwen; Li, Jinhua; Wang, Xiaoyan; Chen, LingxinNature Communications (2022), 13 (1), 5757CODEN: NCAOBW; ISSN:2041-1723. (Nature Portfolio)Chiral discrimination is crit. in environmental and life sciences. However, an ideal chiral discrimination strategy has not yet been developed because of the inevitable nonspecific binding entity of wrong enantiomers or insufficient intrinsic optical activities of chiral mols. Here, we propose an "inspector" recognition mechanism (IRM), which is implemented on a chiral imprinted polydopamine (PDA) layer coated on surface-enhanced Raman scattering (SERS) tag layer. The IRM works based on the permeability change of the imprinted PDA after the chiral recognition and scrutiny of the permeability by an inspector mol. Good enantiomer can specifically recognize and fully fill the chiral imprinted cavities, whereas the wrong cannot. Then a linear shape aminothiol mol., as an inspector of the recognition status is introduced, which can only percolate through the vacant and nonspecifically occupied cavities, inducing the SERS signal to decrease. Accordingly, chirality information exclusively stems from good enantiomer specific binding, while nonspecific recognition of wrong enantiomer is curbed. The IRM benefits from sensitivity and versatility, enabling abs. discrimination of a wide variety of chiral mols. regardless of size, functional groups, polarities, optical activities, Raman scattering, and the no. of chiral centers.
- 141Yang, R.; Zhang, B.; Wang, Y.; Zheng, Y.; Zhang, Q.; Yang, X. Sensitive Determination of Thiram in Apple Samples Using a ZIF-67 Modified Si/Au@Ag Composite as a SERS Substrate. Analytical Methods 2023, 15, 4851– 4861, DOI: 10.1039/D3AY01338CGoogle ScholarThere is no corresponding record for this reference.
- 142Phan-Quang, G. C.; Han, X.; Koh, C. S. L.; Sim, H. Y. F.; Lay, C. L.; Leong, S. X.; Lee, Y. H.; Pazos-Perez, N.; Alvarez-Puebla, R. A.; Ling, X. Y. Three-Dimensional Surface-Enhanced Raman Scattering Platforms: Large-Scale Plasmonic Hotspots for New Applications in Sensing, Microreaction, and Data Storage. Acc. Chem. Res. 2019, 52, 1844– 1854, DOI: 10.1021/acs.accounts.9b00163Google Scholar142Three-Dimensional Surface-Enhanced Raman Scattering Platforms: Large-Scale Plasmonic Hotspots for New Applications in Sensing, Microreaction, and Data StoragePhan-Quang, Gia Chuong; Han, Xuemei; Koh, Charlynn Sher Lin; Sim, Howard Yi Fan; Lay, Chee Leng; Leong, Shi Xuan; Lee, Yih Hong; Pazos-Perez, Nicolas; Alvarez-Puebla, Ramon A.; Ling, Xing YiAccounts of Chemical Research (2019), 52 (7), 1844-1854CODEN: ACHRE4; ISSN:0001-4842. (American Chemical Society)A review. Surface-enhanced Raman scattering (SERS) is a mol.-specific spectroscopic technique that provides up to 1010-fold enhancement of signature Raman fingerprints using nanometer-scale 0D to 2D platforms. Over the past decades, 3D SERS platforms with addnl. plasmonic materials in the z-axis have been fabricated at sub-micrometer to centimeter scale, achieving higher hotspot d. in all x, y, and z spatial directions and higher tolerance to laser misalignment. Moreover, the flexibility to construct platforms in arbitrary sizes and 3D shapes creates attractive applications besides traditional SERS sensing. In this Account, we introduce our library of substrate-based and substrate-less 3D plasmonic platforms, with an emphasis on their non-sensing applications as microlabs. and data storage labels. We aim to provide a scientific synopsis on these high-potential yet currently overlooked applications of SERS and ignite new scientific discoveries and technol. development in 3D SERS platforms to tackle real-world issues. One highlight of our substrate-based SERS platforms is multilayered platforms built from micrometer-thick assemblies of plasmonic particles, which can achieve up to 1011 enhancement factor. As an alternative, constructing 3D hotspots on non-plasmonic supports significantly reduces waste of plasmonic materials while allowing high flexibility in structural design. We then introduce our emerging substrate-less plasmonic capsules including liq. marbles and colloidosomes, which we further incorporate the latter within an aerosol to form centimeter-scale SERS-active plasmonic cloud, the world's largest 3D SERS platform to date. We then discuss the various emerging applications arising only from these 3D platforms, in the fields of sensing, microreactions, and data storage. An important novel sensing application is the stand-off detection of airborne analytes that are several meters away, made feasible with aerosolized plasmonic clouds. We also describe plasmonic capsules as excellent miniature lab-in-droplets that can simultaneously provide in situ monitoring at the mol. level during reaction, owing to their ultrasensitive 3D plasmonic shells. We highlight the emergence of 3D SERS-based data storage platforms with 10-100-fold higher storage d. than 2D platforms, featuring a new approach in the development of level 3 security (L3S) anti-counterfeiting labels. Ultimately, we recognize that 3D SERS research can only be developed further when its sensing capabilities are concurrently strengthened. With this vision, we foresee the creation of highly applicable 3D SERS platforms that excel in both sensing and non-sensing areas, providing modern solns. in the ongoing Fourth Industrial Revolution.
- 143Phan-Quang, G. C.; Yang, N.; Lee, H. K.; Sim, H. Y. F.; Koh, C. S. L.; Kao, Y. C.; Wong, Z. C.; Tan, E. K. M.; Miao, Y. E.; Fan, W.; Liu, T.; Phang, I. Y.; Ling, X. Y. Tracking Airborne Molecules From Afar: Three-Dimensional Metal–Organic Framework-Surface-Enhanced Raman Scattering Platform for Stand-Off and Real-Time Atmospheric Monitoring. ACS Nano 2019, 13, 12090– 12099, DOI: 10.1021/acsnano.9b06486Google Scholar143Tracking Airborne Molecules from Afar: Three-Dimensional Metal-Organic Framework-Surface-Enhanced Raman Scattering Platform for Stand-Off and Real-Time Atmospheric MonitoringPhan-Quang, Gia Chuong; Yang, Ningchen; Lee, Hiang Kwee; Sim, Howard Yi Fan; Koh, Charlynn Sher Lin; Kao, Ya-Chuan; Wong, Zhao Cai; Tan, Eddie Khay Ming; Miao, Yue-E.; Fan, Wei; Liu, Tianxi; Phang, In Yee; Ling, Xing YiACS Nano (2019), 13 (10), 12090-12099CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Stand-off Raman spectroscopy combines advantages of Raman spectroscopy and remote detection to retrieve mol. vibrational fingerprints of chems. at inaccessible sites. It is currently restricted to detecting pure solids and liqs. and is not widely applicable for dispersed mols. in air. This work used real-time, stand-off SERS spectroscopy for remote, multiplex detection of atm. airborne species by integrating a long-range optic system with a three-dimensional (3D) analyte-sorbing metal-org. framework (MOF)-integrated SERS platform. Formed by the self-assembly of Ag@MOF core-shell nanoparticles, this 3D plasmonic architecture exhibited a micrometer-thick SERS hot-spot to allow active sorption and rapid detection of aerosols, gases, and volatile org. compds. down to parts-per-billion concns., notably up to a 10-m apart distance. The platform is highly sensitive to changes in atm. content, as demonstrated in the temporal monitoring of gaseous CO2 over several cycles. Remote, multiplex quantification of polycyclic arom. hydrocarbon mixts. were demonstrated in real time in outdoor sunlight. By overcoming core challenges in current remote Raman spectroscopy, this strategy creates an opportunity for long-distance, sensitive monitoring of air/gaseous environments at the mol. level, particularly important for environmental conservation, disaster prevention, and homeland defense.
- 144Sun, H.; Cong, S.; Zheng, Z.; Wang, Z.; Chen, Z.; Zhao, Z. Metal–Organic Frameworks as Surface Enhanced Raman Scattering Substrates with High Tailorability. J. Am. Chem. Soc. 2019, 141, 870– 878, DOI: 10.1021/jacs.8b09414Google Scholar144Metal-Organic Frameworks as Surface Enhanced Raman Scattering Substrates with High TailorabilitySun, Hongzhao; Cong, Shan; Zheng, Zuhui; Wang, Zhen; Chen, Zhigang; Zhao, ZhigangJournal of the American Chemical Society (2019), 141 (2), 870-878CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Surface enhanced Raman scattering (SERS) is a widely used anal. technique for detecting trace-level mols. based on an indispensable SERS substrate. SERS substrates with high tailorability are assumed to be attractive and desirable for SERS detection, because the substrates match the need for the selective detection of different species. Nevertheless, the rational design of such SERS substrates is rather challenging for both noble-metal and semiconductor substrates. Herein, expanding beyond conventional SERS substrates, we demonstrate that metal-org. framework (MOF) materials can serve as a type of SERS substrate with mol. selectivity, which are rarely realized for SERS detection without any special pretreatment. A salient structural characteristic of MOF-based SERS substrates benefiting the SERS selectivity is their high tailorability. By controlling the metal centers, org. ligands, and framework topologies of our MOF-based SERS substrates, we show that the electronic band structures of MOF-based SERS substrate can be purposively manipulated to match those of the target analytes, thus resulting in different detectable species. Going further, the SERS enhancement factors (EFs) of the MOF-based SERS substrates can be greatly enhanced to as high as 106 with a low detection limit of 10-8 M by pore-structure optimization and surface modification, which is comparable to the EFs of noble metals without "hot spots" and recently reported semiconductors. This selective enhancement is interpreted as being due to the controllable combination of several resonances, such as the charge-transfer, interband and mol. resonances, together with the ground-state charge-transfer interactions. Our study opens a new venue for the development of SERS substrates with high-design flexibility, which is esp. important for selective SERS detection toward specific analytes.
- 145Alvarez-Puebla, R. A.; Liz-Marzán, L. M. SERS Detection of Small Inorganic Molecules and Ions. Angew. Chem., Int. Ed. 2012, 51, 11214– 11223, DOI: 10.1002/anie.201204438Google Scholar145SERS Detection of Small Inorganic Molecules and IonsAlvarez-Puebla, Ramon A.; Liz-Marzan, Luis M.Angewandte Chemie, International Edition (2012), 51 (45), 11214-11223CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. Surface-enhanced Raman scattering (SERS) is one of the most straightforward applications of the so-called nanoplasmonics. This powerful mol. spectroscopy technique is based on the enhancement of the inelastic scattering from mols. located near nanostructured metallic surfaces when these are illuminated and surface plasmons are excited. The anal. applications of SERS are hindered when the Raman cross-section of the analyte is too low, which is often the case in inorg. mol. species. This problem is even more serious when at. species are to be identified, since these cannot display a vibrational signal. Herein the recent advancements toward the SERS detection of small inorg. compds., including both mol. and at. species are discussed.
- 146Xie, X.; Gao, N.; Huang, Y.; Fang, Y. SERS Monitored Kinetic Process of Gaseous Thiophenol Compound in Plasmonic MOF Nanoparticles. ACS Appl. Mater. Interfaces 2022, 14, 51468– 51475, DOI: 10.1021/acsami.2c13820Google Scholar146SERS Monitored Kinetic Process of Gaseous Thiophenol Compound in Plasmonic MOF NanoparticlesXie, Xin; Gao, Nan; Huang, Yingzhou; Fang, YuruiACS Applied Materials & Interfaces (2022), 14 (45), 51468-51475CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Benefiting from the electromagnetic enhancement of noble metal nanoparticles (NPs) and capture ability of org. frameworks, plasmonic metal-org. frameworks (MOFs) structures have greatly promoted the development of gases detection by surface-enhanced Raman spectroscopy (SERS). In those detections, the kinetic process of gaseous mols. in plasmonic-MOF structures has great influence on SERS spectra, which is still lack of intensive investigation in previous reports. In this work, the kinetic processes of gaseous thiophenol compd. (TPC) in plasmonic Zeolitic Imidazolate Framework (Ag@ZIF) core-shell NPs are studied by SERS spectra. The exptl. data demonstrate the SERS intensities of gaseous TPC could be enhanced once more in a H2 mixed gas environment with different functional group of TPC. Further results reveal that the two-step enhancement of SERS intensities is not only related to the thicknesses of MOF Shell, but also effected by the ambient mixed gas. To understand this novel phenomenon, the binding energy between gaseous mol. and ZIF is calcd. based on first-principle computation. Combining with the plasmonic properties of Ag core, a mol. collision model is introduced here to show the distribution of gaseous TPC mols. in ZIF, which could be responsible for this interesting two-step enhancement of SERS intensities. Furthermore, the H2 assisted kinetic process of gaseous p-aminothiophenol (PATP) is also analyzed by the classical pseudo-first-order kinetic model, which is consistent with our exptl. SERS data. Our work not only reveals the novel phenomenon of plasmonic-MOF structures to improve the gases detection by SERS spectra, but also enriches the understanding the microcosmic process of gaseous mols. in mixed gas environment to optimize MOF structures for gas capture and store.
- 147Ji, W.; Zhao, B.; Ozaki, Y. Semiconductor materials in analytical applications of surface-enhanced Raman scattering. J. Raman Spectrosc. 2016, 47, 51– 58, DOI: 10.1002/jrs.4854Google Scholar147Semiconductor materials in analytical applications of surface-enhanced Raman scatteringJi, Wei; Zhao, Bing; Ozaki, YukihiroJournal of Raman Spectroscopy (2016), 47 (1), 51-58CODEN: JRSPAF; ISSN:0377-0486. (John Wiley & Sons Ltd.)Surface-enhanced Raman scattering (SERS) is increasingly becoming an important anal. technique in various fields, which can mostly be attributed to the significant evolution of SERS-active substrates. The semiconductor-based SERS technique is particularly interesting because the inherent physicochem. properties of semiconductor materials offer several possibilities for the development and improvement of SERS-based anal. techniques. According to the effect of the semiconductor materials in SERS, semiconductor-based SERS techniques can be categorized into two areas: (1) semiconductor-enhanced Raman scattering, in which a semiconductor material is directly used as a substrate for enhancing Raman signals of adsorbed mols., and (2) semiconductor-mediated-enhanced Raman scattering, in which a semiconductor is employed as an 'antenna' or 'trap' to modulate the Raman enhancement originating from a metal substrate. While the theory on semiconductor-based SERS is still incomplete and evolving, semiconductor-based SERS techniques have already resulted in substantial progress in biol. anal., photocatalysis, solar cells, sensing, and optoelectronic devices. The aim of this review is to outline the recent progress in this emerging research field, with a special emphasis on its anal. performance and application areas. Copyright © 2015 John Wiley & Sons, Ltd.
- 148Han, X. X.; Ji, W.; Zhao, B.; Ozaki, Y. Semiconductor-enhanced Raman scattering: active nanomaterials and applications. Nanoscale 2017, 9, 4847– 4861, DOI: 10.1039/C6NR08693DGoogle Scholar148Semiconductor-enhanced Raman scattering: active nanomaterials and applicationsHan, Xiao Xia; Ji, Wei; Zhao, Bing; Ozaki, YukihiroNanoscale (2017), 9 (15), 4847-4861CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)Surface-enhanced Raman scattering (SERS)-active nanomaterials have extended from noble metals and transition metals to semiconductor materials, since the first discovery of SERS in the mid-1970s. In comparison with metal substrates and transition metals, semiconductor materials have addnl. optical and elec. properties besides SERS enhancement ability, which enable them to display remarkable charge-transfer enhancement and catalytic ability. Moreover, their superior biocompatibility allows these nanomaterials to have great potential applications in bioscience. Herein we highlight the fast growing research field focusing on SERS-active semiconductor nanomaterials and semiconductor-other material heterostructures developed in our group as well as in other related research studies. The material size, morphol. and assembly-dependent SERS enhancement have been discussed in detail. Furthermore, a variety of promising applications of semiconductor-enhanced Raman scattering in photoelec. characterization, redox biochem., sensing, and the catalytic degrdn. of org. pollutants are introduced.
- 149Lombardi, J. R.; Birke, R. L. Theory of Surface-Enhanced Raman Scattering in Semiconductors. J. Phys. Chem. C 2014, 118, 11120– 11130, DOI: 10.1021/jp5020675Google Scholar149Theory of Surface-Enhanced Raman Scattering in SemiconductorsLombardi, John R.; Birke, Ronald L.Journal of Physical Chemistry C (2014), 118 (20), 11120-11130CODEN: JPCCCK; ISSN:1932-7447. (American Chemical Society)An anal. expression was developed for the lowest order nonzero contribution to the SERS from a system composed of a mol. adsorbed on a semiconductor nanoparticle. A combined mol.-semiconductor system and include Herzberg-Teller vibronic coupling of the zero-order Born-Oppenheimer states are considered. This follows a previous derivation for metallic SERS, but instead of a Fermi level, the semiconductor system involves a band gap and the SERS enhancement is maximized at either the conduction or valence band edge. The resulting expression may be regarded as an extension of the Albrecht A-, B-, and C-terms and show that the SERS enhancement is caused by several resonances in the combined system, namely, surface plasmon, exciton, charge-transfer, and mol. resonances. These resonances are coupled by terms in the numerator, which provide strict selection rules that enable one to test the theory and predict the relative intensities of the Raman lines. By considering interactions of the various contributions to the SERS enhancement, ways were developed to optimize the enhancement factor by tailoring the semiconductor nanostructure thereby adjusting the location of the various contributing resonances.
- 150Alessandri, I.; Lombardi, J. R. Enhanced Raman Scattering with Dielectrics. Chem. Rev. 2016, 116, 14921– 14981, DOI: 10.1021/acs.chemrev.6b00365Google Scholar150Enhanced Raman Scattering with DielectricsAlessandri, Ivano; Lombardi, John R.Chemical Reviews (Washington, DC, United States) (2016), 116 (24), 14921-14981CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review. Dielecs. represent a new frontier for surface-enhanced Raman scattering. They can serve as either a complement or an alternative to conventional, metal-based SERS, offering key advantages in terms of low invasiveness, reproducibility, versatility, and recyclability. In comparison to metals, dielec. systems and, in particular, semiconductors are characterized by a much greater variety of parameters and properties that can be tailored to achieve enhanced Raman scattering or related effects. Light-trapping and subwavelength-focusing capabilities, morphol.-dependent resonances, control of band gap and stoichiometry, size-dependent plasmons and excitons, and charge transfer from semiconductors to mols. and vice versa are a few examples of the manifold opportunities assocd. with the use of semiconductors as SERS-active materials. This review provides a broad anal. of SERS with dielecs., encompassing different optical phenomena at the basis of the Raman scattering enhancement and introducing future challenges for light harvesting, vibrational spectroscopy, imaging, and sensing.
- 151Itoh, T.; Procházka, M.; Dong, Z.-C.; Ji, W.; Yamamoto, Y. S.; Zhang, Y.; Ozaki, Y. Toward a New Era of SERS and TERS at the Nanometer Scale: From Fundamentals to Innovative Applications. Chem. Rev. 2023, 123, 1552– 1634, DOI: 10.1021/acs.chemrev.2c00316Google Scholar151Toward a New Era of SERS and TERS at the Nanometer Scale: From Fundamentals to Innovative ApplicationsItoh, Tamitake; Prochazka, Marek; Dong, Zhen-Chao; Ji, Wei; Yamamoto, Yuko S.; Zhang, Yao; Ozaki, YukihiroChemical Reviews (Washington, DC, United States) (2023), 123 (4), 1552-1634CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review. Surface-enhanced Raman scattering (SERS) and tip-enhanced Raman scattering (TERS) have opened a variety of exciting research fields. However, although a vast no. of applications have been proposed since the two techniques were first reported, none has been applied to real practical use. This calls for an update in the recent fundamental and application studies of SERS and TERS. Thus, the goals and scope of this review are to report new directions and perspectives of SERS and TERS, mainly from the viewpoint of combining their mechanism and application studies. Regarding the recent progress in SERS and TERS, this review discusses four main topics: (1) nanometer to subnanometer plasmonic hotspots for SERS; (2) Ångstrom resolved TERS; (3) chem. mechanisms, i.e., charge-transfer mechanism of SERS and semiconductor-enhanced Raman scattering; and (4) the creation of a strong bridge between the mechanism studies and applications.
- 152Lombardi, J. R.; Birke, R. L. A Unified View of Surface-Enhanced Raman Scattering. Acc. Chem. Res. 2009, 42, 734– 742, DOI: 10.1021/ar800249yGoogle Scholar152A Unified View of Surface-Enhanced Raman ScatteringLombardi, John R.; Birke, Ronald L.Accounts of Chemical Research (2009), 42 (6), 734-742CODEN: ACHRE4; ISSN:0001-4842. (American Chemical Society)A review. In the late 1970s, signal intensity in Raman spectroscopy is enormously enhanced, by a factor of 106 and more recently by ≤1014, when an analyte was placed in the vicinity of a metal nanoparticle (particularly Ag). The underlying source of this huge increase in signal in surface-enhanced Raman scattering (SERS) spectroscopy has since been characterized by considerable controversy. Three possible contributions to the enhancement factor were identified: (i) the surface plasmon resonance in the metal nanoparticle, (ii) a charge-transfer resonance involving transfer of electrons between the mol. and the conduction band of the metal, and (iii) resonances within the mol. itself. These 3 components are often treated as independently contributing to the overall effect, with the implication that by properly choosing the exptl. parameters, ≥1 can be ignored. Although varying exptl. conditions can influence the relative degree to which each resonance influences the total enhancement, higher enhancements can often be obtained by combining ≥2 resonances. Each resonance has a somewhat different effect on the appearance of the resulting Raman spectrum, and it is necessary to invoke ≥1 of these resonances to completely describe a particular expt. However, it is impossible to completely describe all observations of the SERS phenomenon without consideration of all 3 of these contributions. Also, the relative enhancements of individual spectral lines, and therefore the appearance of the spectrum, depend crucially on the exact extent to which each resonance makes a contribution. In this Account, by examg. breakdowns in the Born-Oppenheimer approxn., the authors used Herzberg-Teller coupling to derive a single expression for SERS, which includes contributions from all 3 resonances. Also, these 3 types of resonances are intimately linked by Herzberg-Teller vibronic coupling terms and cannot be considered sep. The authors also examine the differences between SERS and normal Raman spectra. Because of the various resonant contributions, SERS spectra vary with excitation wavelength considerably more than normal Raman spectra. The relative contributions of totally sym. and nontotally sym. lines are also quite different; these differences are due to several effects. The orientation of the mol. with respect to the surface and the inclusion of the metal Fermi level in the list of contributors to the accessible states of the mol.-metal system have a strong influence on the obsd. changes in the Raman spectrum.
- 153Yang, L.; Jiang, X.; Yang, M. Improvement of surface-enhanced Raman scattering performance for broad band gap semiconductor nanomaterial (TiO2): Strategy of metal doping. Appl. Phys. Lett. 2011, 99, 111114, DOI: 10.1063/1.3638467Google Scholar153Improvement of surface-enhanced Raman scattering performance for broad band gap semiconductor nanomaterial (TiO2): Strategy of metal dopingYang, Libin; Jiang, Xin; Yang, MingApplied Physics Letters (2011), 99 (11), 111114/1-111114/3CODEN: APPLAB; ISSN:0003-6951. (American Institute of Physics)The strategy of metal doping was performed to improve surface-enhanced Raman scattering (SERS) performance for semiconductor TiO2 and deeply understand the contributing/controlling factors of semiconductor (TiO2)-to-mol. charge transfer (CT) mechanism contributed to SERS. The amt. and intrinsic nature of doping ions have a great influence on SERS enhancement. An appropriate doping amt. of Fe3+, Co2+, and Ni2+ is 0.5%, 1%, 3% mol., resp., which can enormously improve SERS properties of TiO2 substrate. The considerable SERS enhancement is attributed to doped metal ions, which can embed abundant doping level in TiO2 band gap contributing to semiconductor (TiO2)-to-mol. CT and SERS effect. (c) 2011 American Institute of Physics.
- 154Cong, S.; Yuan, Y.; Chen, Z.; Hou, J.; Yang, M.; Su, Y.; Zhang, Y.; Li, L.; Li, Q.; Geng, F.; Zhao, Z. Noble metal-comparable SERS enhancement from semiconducting metal oxides by making oxygen vacancies. Nat. Commun. 2015, 6, 7800, DOI: 10.1038/ncomms8800Google Scholar154Noble metal-comparable SERS enhancement from semiconducting metal oxides by making oxygen vacanciesCong, Shan; Yuan, Yinyin; Chen, Zhigang; Hou, Junyu; Yang, Mei; Su, Yanli; Zhang, Yongyi; Li, Liang; Li, Qingwen; Geng, Fengxia; Zhao, ZhigangNature Communications (2015), 6 (), 7800CODEN: NCAOBW; ISSN:2041-1723. (Nature Publishing Group)Surface-enhanced Raman spectroscopy (SERS) represents a very powerful tool for the identification of mol. species, but unfortunately it has been essentially restricted to noble metal supports (Au, Ag and Cu). While the application of semiconductor materials as SERS substrate would enormously widen the range of uses for this technique, the detection sensitivity has been much inferior and the achievable SERS enhancement was rather limited, thereby greatly limiting the practical applications. Here, we report the employment of non-stoichiometric tungsten oxide nanostructure, sea urchin-like W18O49 nanowire, as the substrate material, to magnify the substrate-analyte mol. interaction, leading to significant magnifications in Raman spectroscopic signature. The enrichment of surface oxygen vacancy could bring addnl. enhancements. The detection limit concn. was as low as 10-7 M and the max. enhancement factor was 3.4 × 105, in the rank of the highest sensitivity, to our best knowledge, among semiconducting materials, even comparable to noble metals without 'hot spots'.
- 155Liu, H.; Teng, R.; Zhang, S.; Zhao, B.; Ruan, W.; He, D.; Jung, Y. M. Enhancement mechanism of copper ions doped TiO2 substrates based on surface-enhanced raman scattering. Colloids Surf., A 2024, 702, 135152, DOI: 10.1016/j.colsurfa.2024.135152Google ScholarThere is no corresponding record for this reference.
- 156Wang, X.; Guo, L. SERS Activity of Semiconductors: Crystalline and Amorphous Nanomaterials. Angew. Chem., Int. Ed. 2020, 59, 4231– 4239, DOI: 10.1002/anie.201913375Google Scholar156SERS Activity of Semiconductors: Crystalline and Amorphous NanomaterialsWang, Xiaotian; Guo, LinAngewandte Chemie, International Edition (2020), 59 (11), 4231-4239CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. Surface-enhanced Raman scattering (SERS) spectroscopy on semiconductors has attracted increasing attention due to its high spectral reproducibility and unique selectively to target mols. Recently, endeavors have been made in fabricating novel SERS-active semiconductor substrates and exploring new enhancement mechanisms to improve the sensitivity of semiconductor substrates. This Minireview explains the enhancement mechanism of the semiconductor SERS effect in a brief tutorial and summarize recent developments of novel semiconductor substrates, in particular with regard to the remarkable SERS activity of amorphous semiconductor nanomaterials. Potential applications of semiconductor SERS are also a key issue of concern. We discuss a variety of promising applications of semiconductor SERS in the fields of in situ anal. chem., spectroelectrochem. anal., biol. sensing, and trace detection.
- 157Livingstone, R.; Zhou, X. C.; Tamargo, M. C.; Lombardi, J. R.; Quagliano, L. C.; Jean-Mary, F. Surface Enhanced Raman Spectroscopy of Pyridine on CdSe/ZnBeSe Quantum Dots Crown by Molecular Beam Epitaxy. J. Phys. Chem. C 2010, 114, 17460– 17464, DOI: 10.1021/jp105619mGoogle Scholar157Surface Enhanced Raman Spectroscopy of Pyridine on CdSe/ZnBeSe Quantum Dots Grown by Molecular Beam EpitaxyLivingstone, Richard; Zhou, Xuecong; Tamargo, Maria C.; Lombardi, John R.; Quagliano, Lucia G.; Jean-Mary, FleumingueJournal of Physical Chemistry C (2010), 114 (41), 17460-17464CODEN: JPCCCK; ISSN:1932-7447. (American Chemical Society)Using surface enhanced Raman spectroscopy (SERS), the authors obsd. Raman enhancements (104-105) for pyridine mols. adsorbed on II-VI semiconductor quantum dots on (uncapped CdSe/ZnBeSe) produced by MBE. When a monolayer of pyridine is adsorbed on these structures, excitation at 488 nm produces intense Raman spectra, a very large enhancement of the a1, b1, and b2 modes. This indicates charge transfer as a contributor to the enhancement. Also, the excitation wavelength is in the vicinity of several interband transitions located both in the quantum dots and the wetting layer, and probably these resonances also contribute to the enhancement factor.
- 158Yang, L.; Peng, Y.; Yang, Y.; Liu, J.; Huang, H.; Yu, B.; Zhao, J.; Lu, Y.; Huang, Z.; Li, Z.; Lombardi, J. R. A Novel Ultra-Sensitive Semiconductor SERS Substrate Boosted by the Coupled Resonance Effect. Advanced Science 2019, 6, 1900310, DOI: 10.1002/advs.201900310Google Scholar158A Novel Ultra-Sensitive Semiconductor SERS Substrate Boosted by the Coupled Resonance EffectYang Lili; Peng Yusi; Yang Yong; Liu Jianjun; Huang Zhengren; Yang Lili; Peng Yusi; Yang Yong; Yu Bohan; Zhao Jimin; Yang Lili; Peng Yusi; Yang Yong; Huang Haoliang; Lu Yalin; Yu Bohan; Zhao Jimin; Li Zhiyuan; Lombardi John RAdvanced science (Weinheim, Baden-Wurttemberg, Germany) (2019), 6 (12), 1900310 ISSN:2198-3844.Recent achievements in semiconductor surface-enhanced Raman scattering (SERS) substrates have greatly expanded the application of SERS technique in various fields. However, exploring novel ultra-sensitive semiconductor SERS materials is a high-priority task. Here, a new semiconductor SERS-active substrate, Ta2O5, is developed and an important strategy, the "coupled resonance" effect, is presented, to optimize the SERS performance of semiconductor materials by energy band engineering. The optimized Mo-doped Ta2O5 substrate exhibits a remarkable SERS sensitivity with an enhancement factor of 2.2 × 10(7) and a very low detection limit of 9 × 10(-9) m for methyl violet (MV) molecules, demonstrating one of the highest sensitivities among those reported for semiconductor SERS substrates. This remarkable enhancement can be attributed to the synergistic resonance enhancement of three components under 532 nm laser excitation: i) MV molecular resonance, ii) photoinduced charge transfer resonance between MV molecules and Ta2O5 nanorods, and iii) electromagnetic enhancement around the "gap" and "tip" of anisotropic Ta2O5 nanorods. Furthermore, it is discovered that the concomitant photoinduced degradation of the probed molecules in the time-scale of SERS detection is a non-negligible factor that limits the SERS performance of semiconductors with photocatalytic activity.
- 159Jiang, X.; Xu, L.; Ji, W.; Wang, W.; Du, J.; Yang, L.; Song, W.; Han, X.; Zhao, B. One plus one greater than Two: Ultrasensitive Surface-Enhanced Raman scattering by TiO2/ZnO heterojunctions based on Electron-Hole separation. Appl. Surf. Sci. 2022, 584, 152609, DOI: 10.1016/j.apsusc.2022.152609Google Scholar159Ultrasensitive surface-enhanced raman scattering by titanium dioxide/zinc oxide heterojunctions based on electron-hole separationJiang, Xin; Xu, Lin; Ji, Wei; Wang, Weie; Du, Juan; Yang, Libin; Song, Wei; Han, Xiaoxia; Zhao, BingApplied Surface Science (2022), 584 (), 152609CODEN: ASUSEE; ISSN:0169-4332. (Elsevier B.V.)The sepn. of electron-hole pairs has been explored to control the performance of photogenerated carriers in several catalytical and optoelectronic systems, yet its effect on the sensitivity of semiconductor-based surface-enhanced Raman scattering (SERS) is still unknown. Herein, we taken TiO2/ZnO heterojunction as an example to study the role of electron-hole sepn. in semiconductor SERS. The results show that the formation of TiO2/ZnO heterojunction can induce a strong coupling at interface, improving the sepn. of the photogenerated electron-hole pairs. In SERS spectrum, the selective enhancement of non-totally sym. modes (b2) of mol. clearly indicated that the charge-transfer efficiency and SERS-activity can be significantly improved using such a semiconductor-heterojunction. Furthermore, the enhancement factor of 105 was achieved for a non-resonance mol. and the lowest detection concn. can be down to 10-8 M. The findings of this work not only provide a fundamental insight into the role of electron-hole sepn. for semiconductor SERS enhancement, but also open up a novel strategy for design of semiconductor SERS-active substrate with a high charge-transfer contribution.
- 160Zhang, H.; Tang, Y.; Wang, W.; Yu, D.; Yang, L.; Jiang, X.; Song, W.; Zhao, B. A new semiconductor heterojunction SERS substrate for ultra-sensitive detection of antibiotic residues in egg. Food Chem. 2024, 431, 137163, DOI: 10.1016/j.foodchem.2023.137163Google ScholarThere is no corresponding record for this reference.
- 161Jiang, X.; He, S.; Tang, Y.; Wang, X.; Zhang, H.; Yang, L.; Kan, W.; Zhao, B. High energy facet-dominated TiO2–X facet heterojunction with excellent carrier utilization for ultrasensitive SERS sensing and efficient degradation of antibiotic residues. Sens. Actuators, B 2024, 403, 135241, DOI: 10.1016/j.snb.2023.135241Google ScholarThere is no corresponding record for this reference.
- 162Zhu, L.; Meng, Z.; Zhao, T.; Wang, Y.; Zhao, B. Dye-Sensitized Solar Cells Inspired Method to Modulate Photo-Induced Charge Transfer Efficiency for Enhancing the SERS Activity of Semiconductor. Advanced Materials Interfaces 2023, 2300548, DOI: 10.1002/admi.202300548Google ScholarThere is no corresponding record for this reference.
- 163Rodriguez, I.; Shi, L.; Lu, X.; Korgel, B. A.; Alvarez-Puebla, R. A.; Meseguer, F. Silicon nanoparticles as Raman scattering enhancers. Nanoscale 2014, 6, 5666– 5670, DOI: 10.1039/C4NR00593GGoogle Scholar163Silicon nanoparticles as Raman scattering enhancersRodriguez, I.; Shi, L.; Lu, X.; Korgel, B. A.; Alvarez-Puebla, R. A.; Meseguer, F.Nanoscale (2014), 6 (11), 5666-5670CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)In this communication we demonstrate the large amplification values of the Raman signal of org. mols. attached to silicon nanoparticles (SiNPs). Light induced Mie resonances of high refractive index particles generate strong evanescent electromagnetic (EM) fields, thus boosting the Raman signal of species attached to the nanoparticles. The interest of this process is justified by the wide range of exptl. configurations that can be implemented including photonic crystals, the sharp spectral resonances easily tuneable with the particle size, the biocompatibility and biodegradability of silicon, and the possibility of direct anal. of mols. that do not contain functional groups with high affinity for gold and silver. Addnl., silicon nanoparticles present stronger field enhancement due to Mie resonances at larger sizes than gold.
- 164Öner, I. H.; Querebillo, C. J.; David, C.; Gernert, U.; Walter, C.; Driess, M.; Leimkühler, S.; Ly, K. H.; Weidinger, I. M. High Electromagnetic Field Enhancement of TiO2 Nanotube Electrodes. Angew. Chem., Int. Ed. 2018, 57, 7225– 7229, DOI: 10.1002/anie.201802597Google Scholar164High Electromagnetic Field Enhancement of TiO2 Nanotube ElectrodesOner Ibrahim Halil; Weidinger Inez M; Querebillo Christine Joy; Walter Carsten; Driess Matthias; David Christin; Gernert Ulrich; Leimkuhler Silke; Ly Khoa HoangAngewandte Chemie (International ed. in English) (2018), 57 (24), 7225-7229 ISSN:.We present the fabrication of TiO2 nanotube electrodes with high biocompatibility and extraordinary spectroscopic properties. Intense surface-enhanced resonance Raman signals of the heme unit of the redox enzyme Cytochrome b5 were observed upon covalent immobilization of the protein matrix on the TiO2 surface, revealing overall preserved structural integrity and redox behavior. The enhancement factor could be rationally controlled by varying the electrode annealing temperature, reaching a record maximum value of over 70 at 475 °C. For the first time, such high values are reported for non-directly surface-interacting probes, for which the involvement of charge-transfer processes in signal amplification can be excluded. The origin of the surface enhancement is exclusively attributed to enhanced localized electric fields resulting from the specific optical properties of the nanotubular geometry of the electrode.
- 165Han, X. X.; Köhler, C.; Kozuch, J.; Kuhlmann, U.; Paasche, L.; Sivanesan, A.; Weidinger, I. M.; Hildebrandt, P. Potential-Dependent Surface-Enhanced Resonance Raman Spectroscopy at Nanostructured TiO2: A Case Study on Cytochrome b5. Small 2013, 9, 4175– 4181, DOI: 10.1002/smll.201301070Google Scholar165Potential-Dependent Surface-Enhanced Resonance Raman Spectroscopy at Nanostructured TiO2: A Case Study on Cytochrome b5Han, Xiao Xia; Koehler, Christopher; Kozuch, Jacek; Kuhlmann, Uwe; Paasche, Lars; Sivanesan, Arumugam; Weidinger, Inez M.; Hildebrandt, PeterSmall (2013), 9 (24), 4175-4181CODEN: SMALBC; ISSN:1613-6810. (Wiley-VCH Verlag GmbH & Co. KGaA)Nanostructured titanium dioxide (TiO2) electrodes, prepd. by anodization of titanium, are employed to probe the electron-transfer process of cytochrome b5 (cyt b5) by surface-enhanced resonance Raman (SERR) spectroscopy. Concomitant with the increased nanoscopic surface roughness of TiO2, achieved by raising the anodization voltage from 10 to 20 V, the enhancement factor increases from 2.4 to 8.6, which is rationalized by calcns. of the elec. field enhancement. Cyt b5 is immobilized on TiO2 under preservation of its native structure but it displays a non-ideal redox behavior due to the limited cond. of the electrode material. The electron-transfer efficiency which depends on the cryst. phase of TiO2 has to be improved by appropriate doping for applications in bioelectrochem.
- 166Alessandri, I. Enhancing Raman Scattering without Plasmons: Unprecedented Sensitivity Achieved by TiO2 Shell-Based Resonators. J. Am. Chem. Soc. 2013, 135, 5541– 5544, DOI: 10.1021/ja401666pGoogle Scholar166Enhancing Raman Scattering without Plasmons: Unprecedented Sensitivity Achieved by TiO2 Shell-Based ResonatorsAlessandri, IvanoJournal of the American Chemical Society (2013), 135 (15), 5541-5544CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)A remarkable enhancement of Raman scattering is achieved by TiO2 shell-based spherical resonators in the absence of plasmonic enhancers. This effect is ascribed to the synergistic combination of high refractive index of the shell layer, multiple light scattering through the spheres, and related geometrical factors and can be exploited to fabricate a new generation of self-diagnostic, recyclable SERS-active substrates.
- 167Qi, D.; Lu, L.; Wang, L.; Zhang, J. Improved SERS Sensitivity on Plasmon-Free TiO2 Photonic Microarray by Enhancing Light-Matter Coupling. J. Am. Chem. Soc. 2014, 136, 9886– 9889, DOI: 10.1021/ja5052632Google Scholar167Improved SERS Sensitivity on Plasmon-Free TiO2 Photonic Microarray by Enhancing Light-Matter CouplingQi, Dianyu; Lu, Liujia; Wang, Lingzhi; Zhang, JinlongJournal of the American Chemical Society (2014), 136 (28), 9886-9889CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Highly sensitive surface-enhanced Raman scattering (SERS) detection was achieved on plasmon-free TiO2 photonic artificial microarray, which can be quickly recovered under simulated solar light irradn. and repeatedly used. The sensitive detection performance is attributed to the enhanced matter-light interaction through repeated and multiple light scattering in photonic microarray. The SERS sensitivity is unprecedentedly found to be dependent on the different light-coupling performance of microarray with various photonic band gaps, where microarray with band gap center near to laser wavelength shows a lower SERS signal due to depressed light propagation, while those with band gap edges near to laser wavelength show higher sensitivity due to slow light effect.
- 168Ji, W.; Li, L.; Song, W.; Wang, X.; Zhao, B.; Ozaki, Y. Enhanced Raman Scattering by ZnO Superstructures: Synergistic Effect of Charge Transfer and Mie Resonances. Angew. Chem., Int. Ed. 2019, 58, 14452– 14456, DOI: 10.1002/anie.201907283Google Scholar168Enhanced Raman Scattering by ZnO Superstructures: Synergistic Effect of Charge Transfer and Mie ResonancesJi, Wei; Li, Linfang; Song, Wei; Wang, Xinnan; Zhao, Bing; Ozaki, YukihiroAngewandte Chemie, International Edition (2019), 58 (41), 14452-14456CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)A remarkable enhancement of Raman scattering is achieved by sub-μm-sized spherical ZnO superstructures. The secondary superstructures of ZnO particles with a uniform diam. at 220-490 nm was formed by aggregating ∼13 nm primary single crystallites. By engineering the superstructure size to induce Mie resonances, leading to an electromagnetic contribution to the SERS enhancement. A highly efficient charge-transfer (CT) contribution derived from the primary structure of the ZnO nanocrystallites was able to enhance the SERS signals as well. The highest Raman enhancement factor of 105 was achieved for a nonresonant mol. by the synergistic effect of CT and Mie resonances. The Mie resonances scattered near-field effect studied in the present study provides not only an important guide for designing novel SERS-active semiconductor substrates, but also a coherent framework for modeling the electromagnetic mechanism of SERS on semiconductors.
- 169Liu, X.; Ye, Z.; Xiang, Q.; Xu, Z.; Yue, W.; Li, C.; Xu, Y.; Wang, L.; Cao, X.; Zhang, J. Boosting electromagnetic enhancement for detection of non-adsorbing analytes on semiconductor SERS substrates. Chem. 2023, 9, 1464– 1476, DOI: 10.1016/j.chempr.2023.01.017Google ScholarThere is no corresponding record for this reference.
- 170Ji, W.; Li, L.; Guan, J.; Mu, M.; Song, W.; Sun, L.; Zhao, B.; Ozaki, Y. Hollow Multi-Shelled V2O5 Microstructures Integrating Multiple Synergistic Resonances for Enhanced Semiconductor SERS. Advanced Optical Materials 2021, 9, 2101866, DOI: 10.1002/adom.202101866Google ScholarThere is no corresponding record for this reference.
- 171Li, J.; Xie, Q.; Li, J.; Sun, L.; Xie, Y.; Ozaki, Y.; Ji, W. Macroscale TiO2 Microspherical Arrays with Multiple Synergistic Effect for Highly Sensitive Surface-Enhanced Raman Scattering. Adv. Funct. Mater. 2024, 34, 2400523, DOI: 10.1002/adfm.202400523Google ScholarThere is no corresponding record for this reference.
- 172Mu, M.; Wen, S.; Hu, S.; Zhao, B.; Song, W. Putting surface-enhanced Raman spectroscopy to work for nanozyme research: Methods, materials and applications. TrAC Trends in Analytical Chemistry 2022, 152, 116603, DOI: 10.1016/j.trac.2022.116603Google ScholarThere is no corresponding record for this reference.
- 173Zhang, Y.; Yang, T.; Li, J.; Zhang, Q.; Li, B.; Gao, M. Construction of Ru, O Co-Doping MoS2 for Hydrogen Evolution Reaction Electrocatalyst and Surface-Enhanced Raman Scattering Substrate: High-Performance, Recyclable, and Durability Improvement. Adv. Funct. Mater. 2023, 33, 2210939, DOI: 10.1002/adfm.202210939Google ScholarThere is no corresponding record for this reference.
- 174Zheng, X.; Ye, Z.; Akmal, Z.; He, C.; Zhang, J.; Wang, L. Recent progress in SERS monitoring of photocatalytic reactions. Chem. Soc. Rev. 2024, 53, 656– 683, DOI: 10.1039/D3CS00462GGoogle ScholarThere is no corresponding record for this reference.
- 175Fan, K. L.; Gao, L. Z.; Wei, H.; Jiang, B.; Wang, D. J.; Zhang, R. F.; He, J. Y.; Meng, X. Q.; Wang, Z. R.; Fan, H. Z.; Wen, T.; Duan, D. M.; Chen, L.; Jiang, W.; Lu, Y.; Jiang, B.; Wei, Y. H.; Li, W.; Yuan, Y.; Dong, H. J.; Zhang, L.; Hong, C. Y.; Zhang, Z. X.; Cheng, M. M.; Geng, X.; Hou, T. Y.; Hou, Y. X.; Li, J. R.; Tang, G. H.; Zhao, Y.; Zhao, H. Q.; Zhang, S.; Xie, J. Y.; Zhou, Z. J.; Ren, J. S.; Huang, X. L.; Gao, X. F.; Liang, M. M.; Zhang, Y.; Xu, H. Y.; Qu, X. G.; Yan, X. Y. Nanozymes. Progress in Chemistry 2023, 35, 1– 87, DOI: 10.7536/PC220833Google ScholarThere is no corresponding record for this reference.
- 176Jin, J.; Song, W.; Wang, J. Q.; Li, L. J.; Tian, Y.; Zhu, S. J.; Zhang, Y. P.; Xu, S. P.; Yang, B.; Zhao, B. A highly sensitive SERS platform based on small-sized Ag/GQDs nanozyme for intracellular analysis. Chemical Engineering Journal 2022, 430, 132687, DOI: 10.1016/j.cej.2021.132687Google ScholarThere is no corresponding record for this reference.
- 177Zhao, Q. N.; Cheng, X. H.; Hu, S. Z.; Zhao, M. H.; Chen, J. J.; Mu, M.; Yang, Y. M.; Liu, H.; Hu, L. H.; Zhao, B.; Song, W. Bilateral efforts to improve SERS detection efficiency of exosomes by Au/ Na7PMo11O39 Combined with Phospholipid Epitope Imprinting. Biosens. Bioelectron. 2024, 258, 116349, DOI: 10.1016/j.bios.2024.116349Google ScholarThere is no corresponding record for this reference.
- 178Wen, S. S.; Ma, X. W.; Liu, H.; Chen, G.; Wang, H.; Deng, G. Q.; Zhang, Y. T.; Song, W.; Zhao, B.; Ozaki, Y. Accurate Monitoring Platform for the Surface Catalysis of Nanozyme Validated by Surface-Enhanced Raman-Kinetics Model. Anal. Chem. 2020, 92, 11763– 11770, DOI: 10.1021/acs.analchem.0c01886Google Scholar178Accurate Monitoring Platform for the Surface Catalysis of Nanozyme Validated by Surface-Enhanced Raman-Kinetics ModelWen, Sisi; Ma, Xiaowei; Liu, Hao; Chen, Gang; Wang, He; Deng, Gaoqiang; Zhang, Yuantao; Song, Wei; Zhao, Bing; Ozaki, YukihiroAnalytical Chemistry (Washington, DC, United States) (2020), 92 (17), 11763-11770CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Surface-enhanced Raman scattering (SERS) is a supersensitive technique for monitoring catalytic reactions. However, building a SERS-kinetics model to study catalytic efficiency on the surface or interface of the catalyst remains a great challenge. The authors successfully obtained an excellent semiconducting SERS substrate, reduced MnCo2O4 (R-MnCo2O4) nanotubes, whose favorable SERS sensitivity is mainly related to the promoted interfacial charge transfer caused by the introduction of oxygen vacancies as well as the electromagnetic enhancement effect. Also, the R-MnCo2O4 nanotubes showed a favorable oxidase-like activity toward oxidn. with the aid of O2. It was also showed the oxidase-like catalytic process could be monitored using the SERS technique. A new SERS-kinetics model to monitor the catalytic efficiency of the oxidase-like reaction was developed, and the Vm values measured by the SERS-kinetics method are close to that obtained by the UV-visible approach, while the Km values measured by the SERS-kinetics method are much lower, demonstrating the better affinity between the enzyme and the substrate from SERS results and further confirming the high sensitivity of the SERS-kinetics approach and the actual enzyme-like reaction on the surface of nanozymes, which provides guidance in understanding the kinetics process and catalytic mechanism of natural enzymic and other artificial enzymic reactions. This work demonstrated the improved SERS sensitivity of defective semiconductors for the application of enzyme mimicking, providing a new frontier to construct highly sensitive biosensors.
- 179Wen, S. S.; Jiang, W. J.; Yang, Y. M.; Shang, L. J.; Wang, X.; Zhao, B.; Song, W. Research on Surface-Enhanced Raman Spectroscopy and Simulated Laccase Activity of Two-Dimensional Metal Sulfide Nanosheets. J. Phys. Chem. C 2024, 128, 4224– 4232, DOI: 10.1021/acs.jpcc.4c00844Google ScholarThere is no corresponding record for this reference.
- 180Huang, L. J.; Sun, D. W.; Pu, H. B.; Wei, Q. Y.; Luo, L. P.; Wang, J. L. A colorimetric paper sensor based on the domino reaction of acetylcholinesterase and degradable γ-MnOOH nanozyme for sensitive detection of organophosphorus pesticides. Sensors and Actuators B-Chemical 2019, 290, 573– 580, DOI: 10.1016/j.snb.2019.04.020Google ScholarThere is no corresponding record for this reference.
- 181Xi, H. Y.; Gu, H. F.; Han, Y. R.; You, T. T.; Wu, P. F.; Liu, Q. Q.; Zheng, L. R.; Liu, S. H.; Fu, Q.; Chen, W. X.; Gao, Y. K.; Wang, Y. T.; Yin, P. G. Peroxidase-like single Fe atoms anchored on Ti3C2Tx MXene as surface enhanced Raman scattering substrate for the simultaneous discrimination of multiple antioxidants. Nano Research 2023, 16, 10053– 10060, DOI: 10.1007/s12274-023-5739-2Google ScholarThere is no corresponding record for this reference.
- 182Chen, Y.; Zhang, J.; Li, J. Y.; Hu, Y. L.; Ge, K.; Li, G. K.; Liu, S. C. Bifunctional Mo2N Nanoparticles with Nanozyme and SERS Activity: A Versatile Platform for Sensitive Detection of Biomarkers in Serum Samples. Anal. Chem. 2024, 96, 2998– 3007, DOI: 10.1021/acs.analchem.3c04801Google ScholarThere is no corresponding record for this reference.
- 183Yang, Y.; Wang, C.; Wang, N.; Li, J.; Zhu, Y.; Zai, J.; Fu, J.; Hao, Y. Photogenerated reactive oxygen species and hyperthermia by Cu3SnS4 nanoflakes for advanced photocatalytic and photothermal antibacterial therapy. J. Nanobiotechnol. 2022, 20, 195, DOI: 10.1186/s12951-022-01403-yGoogle ScholarThere is no corresponding record for this reference.
- 184Lin, L.; Bi, X.; Gu, Y.; Wang, F.; Ye, J. Surface-enhanced Raman scattering nanotags for bioimaging. J. Appl. Phys. 2021, 129, 191101, DOI: 10.1063/5.0047578Google Scholar184Surface-enhanced Raman scattering nanotags for bioimagingLin, Li; Bi, Xinyuan; Gu, Yuqing; Wang, Fu; Ye, JianJournal of Applied Physics (Melville, NY, United States) (2021), 129 (19), 191101CODEN: JAPIAU; ISSN:0021-8979. (American Institute of Physics)A review. Surface-enhanced Raman scattering (SERS) technique has shown extraordinary features for biomedical applications. The implementation of SERS nanotags has opened a new era for bioimaging and detections. As a powerful tool, SERS nanotags provide favorable properties such as fingerprint spectrum, narrow peak linewidth, good photostability, and high spatial resoln. accompanied by various rational designs of nanoparticles. They have proven as useful imaging agents for in vivo, ex vivo, and in vitro detection of cancerous cells and tissues. This tutorial provides the basic principles of SERS and SERS nanotags, including recent progress of SERS-based bioimaging applications, as well as the outlooks into the future developments toward practical clin. SERS. (c) 2021 American Institute of Physics.
- 185Jin, X.; He, J.; Ye, J. Nanotriangle-based gap-enhanced Raman tags for bioimaging and photothermal therapy. J. Appl. Phys. 2019, 125, 073102, DOI: 10.1063/1.5081891Google Scholar185Nanotriangle-based gap-enhanced Raman tags for bioimaging and photothermal therapyJin, Xiulong; He, Jing; Ye, JianJournal of Applied Physics (Melville, NY, United States) (2019), 125 (7), 073102/1-073102/11CODEN: JAPIAU; ISSN:0021-8979. (American Institute of Physics)Surface-enhanced Raman scattering (SERS) nanoparticles can be utilized as optical labeling nanoprobes for bioimaging with advantages of the fingerprint vibrational signal as a unique optical code and the ultra-narrow linewidth for multiplexing. As a new type of SERS nanoprobes, gap-enhanced Raman tags (GERTs) developed recently can overcome the common issues of poor photostability and limited Raman enhancement. In this work, we have constructed bright nanotriangle-based GERTs (NT-GERTs) for combined SERS bioimaging and photothermal therapy. With optimized Au shell morphol. and thickness, NT-GERTs possess 20 folds brighter SERS signal and a more efficient photothermal effect compared to conventional nanosphere-based GERTs. These NT-GERTs show great potential for intraoperative SERS bioimaging guided photothermal therapy of cancers. (c) 2019 American Institute of Physics.
- 186Gurav, D. D.; Jia, Y. A.; Ye, J.; Qian, K. Design of plasmonic nanomaterials for diagnostic spectrometry. Nanoscale Advances 2019, 1, 459– 469, DOI: 10.1039/C8NA00319JGoogle ScholarThere is no corresponding record for this reference.
- 187Gu, Y.; Bi, X.; Ye, J. Gap-enhanced resonance Raman tags for live-cell imaging. J. Mater. Chem. B 2020, 8, 6944– 6955, DOI: 10.1039/D0TB00659AGoogle Scholar187Gap-enhanced resonance Raman tags for live-cell imagingGu, Yuqing; Bi, Xinyuan; Ye, JianJournal of Materials Chemistry B: Materials for Biology and Medicine (2020), 8 (31), 6944-6955CODEN: JMCBDV; ISSN:2050-7518. (Royal Society of Chemistry)Surface-enhanced Raman scattering (SERS) nanotags are widely used in the biomedical field including live-cell imaging due to the high specificity from their fingerprint spectrum and the multiplexing capability from the ultra-narrow linewidth. However, long-term live-cell Raman imaging is limited due to the photodamage from a relatively long exposure time and a high laser power, which are needed for acquiring detectable Raman signals. The authors attempt to resolve this issue by developing ultrabright gap-enhanced resonance Raman tags (GERRTs), consisting of a petal-like gold core and a silver shell with the near-IR resonant reporter of IR-780 embedded in between, for long-term and high-speed live-cell imaging. GERRTs exhibit an ultrahigh Raman intensity down to a single-nanoparticle level in aq. soln. and the solid state upon 785 nm excitation, allowing for high-resoln. time-lapse live-cell Raman imaging with an exposure time of 1 ms per pixel and a laser power of 50μW. Under these measurement conditions, the authors can possibly capture dynamic cellular processes with a high temporal resoln., and track living cells for long periods of time owing to the reduced photodamage to cells. These nanotags open new opportunities for ultrasensitive, low-phototoxic, and long-term live-cell imaging.
- 188Liu, H.; Gao, X.; Xu, C.; Liu, D. SERS Tags for Biomedical Detection and Bioimaging. Theranostics 2022, 12, 1870– 1903, DOI: 10.7150/thno.66859Google Scholar188SERS tags for biomedical detection and bioimagingLiu, Huiqiao; Gao, Xia; Xu, Chen; Liu, DingbinTheranostics (2022), 12 (4), 1870-1903CODEN: THERDS; ISSN:1838-7640. (Ivyspring International Publisher)A review. Surface-enhanced Raman scattering (SERS) has emerged as a valuable technique for mol. identification. Due to the characteristics of high sensitivity, excellent signal specificity, and photobleaching resistance, SERS has been widely used in the fields of environmental monitoring, food safety, and disease diagnosis. By attaching the org. mols. to the surface of plasmonic nanoparticles, the obtained SERS tags show high-performance multiplexing capability for biosensing. The past decade has witnessed the progress of SERS tags for liq. biopsy, bioimaging, and theranostics applications. This review focuses on the advances of SERS tags in biomedical fields. We first introduce the building blocks of SERS tags, followed by the summarization of recent progress in SERS tags employed for detecting biomarkers, such as DNA, miRNA, and protein in biol. fluids, as well as imaging from in vitro cell, bacteria, tissue to in vivo tumors. Further, we illustrate the appealing applications of SERS tags for delineating tumor margins and cancer diagnosis. In the end, perspectives of SERS tags projecting into the possible obstacles are deliberately proposed in future clin. translation.
- 189Zhang, Y.; Gu, H.; Wu, Z.; Ye, J.; Lin, L. L. Nanoengineering for gap-enhanced Raman tags and related plasmonic applications. Ramamurthy, S. S.; Bhaskar, S.; Reddy, N., Eds.; In Micro and Nano Technologies, Nano-Engineering at Functional Interfaces for Multi-Disciplinary Applications; Elsevier: 2025; pp 75– 91, https://doi.org/10.1016/B978-0-443-21691-6.00005-6.Google ScholarThere is no corresponding record for this reference.
- 190Lim, D.-K.; Jeon, K.-S.; Hwang, J.-H.; Kim, H.; Kwon, S.; Suh, Y. D.; Nam, J.-M. Highly uniform and reproducible surface-enhanced Raman scattering from DNA-tailorable nanoparticles with 1-nm interior gap. Nat. Nanotechnol. 2011, 6, 452– 460, DOI: 10.1038/nnano.2011.79Google Scholar190Highly uniform and reproducible surface-enhanced Raman scattering from DNA-tailorable nanoparticles with 1-nm interior gapLim, Dong-Kwon; Jeon, Ki-Seok; Hwang, Jae-Ho; Kim, Hyoki; Kwon, Sunghoon; Suh, Yung Doug; Nam, Jwa-MinNature Nanotechnology (2011), 6 (7), 452-460CODEN: NNAABX; ISSN:1748-3387. (Nature Publishing Group)An ideal surface-enhanced Raman scattering (SERS) nanostructure for sensing and imaging applications should induce a high signal enhancement, generate a reproducible and uniform response, and should be easy to synthesize. Many SERS-active nanostructures have been investigated, but they suffer from poor reproducibility of the SERS-active sites, and the wide distribution of their enhancement factor values results in an unquantifiable SERS signal. Here, we show that DNA on gold nanoparticles facilitates the formation of well-defined gold nanobridged nanogap particles (Au-NNP) that generate a highly stable and reproducible SERS signal. The uniform and hollow gap (∼1 nm) between the gold core and gold shell can be precisely loaded with a quantifiable amt. of Raman dyes. SERS signals generated by Au-NNPs showed a linear dependence on probe concn. (R2 > 0.98) and were sensitive down to 10fM concns. Single-particle nano-Raman mapping anal. revealed that >90% of Au-NNPs had enhancement factors greater than 1.0 × 108, which is sufficient for single-mol. detection, and the values were narrowly distributed between 1.0 × 108 and 5.0 × 109.
- 191Zhang, Y.; Gu, Y.; He, J.; Thackray, B. D.; Ye, J. Ultrabright gap-enhanced Raman tags for high-speed bioimaging. Nat. Commun. 2019, 10, 3905, DOI: 10.1038/s41467-019-11829-yGoogle Scholar191Ultrabright gap-enhanced Raman tags for high-speed bioimagingZhang Yuqing; Gu Yuqing; He Jing; Thackray Benjamin D; Ye Jian; Zhang Yuqing; Ye Jian; Ye JianNature communications (2019), 10 (1), 3905 ISSN:.Surface-enhanced Raman spectroscopy (SERS) is advantageous over fluorescence for bioimaging due to ultra-narrow linewidth of the fingerprint spectrum and weak photo-bleaching effect. However, the existing SERS imaging speed lags far behind practical needs, mainly limited by Raman signals of SERS nanoprobes. In this work, we report ultrabright gap-enhanced Raman tags (GERTs) with strong electromagnetic hot spots from interior sub-nanometer gaps and external petal-like shell structures, larger immobilization surface area, and Raman cross section of reporter molecules. These GERTs reach a Raman enhancement factor beyond 5 × 10(9) and a detection sensitivity down to a single-nanoparticle level. We use a 370 μW laser to realize high-resolution cell imaging within 6 s and high-contrast (a signal-to-background ratio of 80) wide-area (3.2 × 2.8 cm(2)) sentinel lymph node imaging within 52 s. These nanoprobes offer a potential solution to overcome the current bottleneck in the field of SERS-based bioimaging.
- 192Lin, L.; Gu, H.; Ye, J. Plasmonic multi-shell nanomatryoshka particles as highly tunable SERS tags with built-in reporters. Chem. Commun. (Camb) 2015, 51, 17740– 3, DOI: 10.1039/C5CC06599BGoogle Scholar192Plasmonic multi-shell nanomatryoshka particles as highly tunable SERS tags with built-in reportersLin, Li; Gu, Hongchen; Ye, JianChemical Communications (Cambridge, United Kingdom) (2015), 51 (100), 17740-17743CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)The synthesis and averaged SERS measurements of multi-shell nanomatryoshka SERS tags are reported. By tuning the no. of shells or by changing the Raman reporters in different gap layers, their Raman intensities and spectral bands were tunable. These tags show great potential for SERS-based biosensing and bioimaging.
- 193Gu, Y.; He, C.; Liu, F.; Ye, J. Raman ink for steganography. Advanced Optical Materials 2021, 9, 2002038, DOI: 10.1002/adom.202002038Google ScholarThere is no corresponding record for this reference.
- 194Gu, Y.; He, C.; Zhang, Y.; Lin, L.; Thackray, B. D.; Ye, J. Gap-enhanced Raman tags for physically unclonable anticounterfeiting labels. Nat. Commun. 2020, 11, 516, DOI: 10.1038/s41467-019-14070-9Google Scholar194Gap-enhanced Raman tags for physically unclonable anticounterfeiting labelsGu, Yuqing; He, Chang; Zhang, Yuqing; Lin, Li; Thackray, Benjamin David; Ye, JianNature Communications (2020), 11 (1), 516CODEN: NCAOBW; ISSN:2041-1723. (Nature Research)Abstr.: Anticounterfeiting labels based on phys. unclonable functions (PUFs), as one of the powerful tools against counterfeiting, are easy to generate but difficult to duplicate due to inherent randomness. Gap-enhanced Raman tags (GERTs) with embedded Raman reporters show strong intensity enhancement and ultra-high photostability suitable for fast and repeated readout of PUF labels. Herein, we demonstrate a PUF label fabricated by drop-casting aq. GERTs, high-speed read using a confocal Raman system, digitized through coarse-grained coding methods, and authenticated via pixel-by-pixel comparison. A three-dimensional encoding capacity of over 3 × 1015051 can be achieved for the labels composed of ten types of GERTs with a mapping resoln. of 2500 pixels and quaternary encoding of Raman intensity levels at each pixel. Authentication expts. have ensured the robustness and security of the PUF system, and the practical viability is demonstrated. Such PUF labels could provide a potential platform to realize unbreakable anticounterfeiting.
- 195Chen, M.; Wang, J.; Li, D.; Wang, B.; Wang, S.; Zhao, X.; Meng, M. High-speed and wide-field 3D Raman imaging using flower-like gap-enhanced Raman tags. Appl. Phys. Lett. 2024, 124, 123701, DOI: 10.1063/5.0190009Google ScholarThere is no corresponding record for this reference.
- 196Jiang, X.; Tan, Z.; Lin, L.; He, J.; He, C.; Thackray, B. D.; Zhang, Y.; Ye, J. Surface-Enhanced Raman Nanoprobes with Embedded Standards for Quantitative Cholesterol Detection. Small Methods 2018, 2, 1800182, DOI: 10.1002/smtd.201800182Google ScholarThere is no corresponding record for this reference.
- 197Zhou, Y.; Zhang, Y.; Xie, H.; Wu, Z.; Shi, B.; Lin, L. L.; Ye, J. In Vivo Surface-Enhanced Transmission Raman Spectroscopy and Impact of Frozen Biological Tissues on Lesion Depth Prediction. ACS Nano 2024, 18 (52), 35393– 35404, DOI: 10.1021/acsnano.4c12469Google ScholarThere is no corresponding record for this reference.
- 198Tu, D.; Holderby, A.; Guo, H.; Mabbott, S.; Tian, L.; Coté, G. L. Spectrally multiplexed assay using gap enhanced nanoparticle for detection of a myocardial infarction biomarker panel. Anal. Chim. Acta 2022, 1198, 339562, DOI: 10.1016/j.aca.2022.339562Google Scholar198Spectrally multiplexed assay using gap enhanced nanoparticle for detection of a myocardial infarction biomarker panelTu, Dandan; Holderby, Allison; Guo, Heng; Mabbott, Samuel; Tian, Limei; Cote, Gerard L.Analytica Chimica Acta (2022), 1198 (), 339562CODEN: ACACAM; ISSN:0003-2670. (Elsevier B.V.)Multiplexed assays are essential for the detection of biomarker panels. Differentiating signals from different biomarkers in a single test zone makes the detection more efficient. In this paper, a new method is designed for the synthesis of gap-enhanced nanoparticles (GeNPs) using Raman reporter mols. (RRM) and 6-amino-1-hexanethiol (6-AHT) as the spacer. The GeNPs show a nanometer-size gap, generate strong surface-enhanced Raman scattering (SERS) attributed to the gap, and exhibit discriminative spectral peaks. The strong Au-S bonds on both core and shell sides and the covalent bond between RRM and 6-AHT led to a stable structure, which ensured the stable SERS signal generation from the GeNPs. Using the GeNPs, a spectrally multiplexed assay for the detection of a biomarker panel is developed. The biomarker panel is composed of cardiac troponin I (cTnI), copeptin, and heart-type fatty acid-binding protein (h-FABP), which improves myocardial infarction (MI) diagnostic performance. A paper-based platform that is more amenable to point-of-care diagnostic anal. is used. The developed single biomarker assay achieves limits of detection of 0.01 ng mL-1, 0.86 ng mL-1, 0.004 ng mL-1 for cTnI, h-FABP, and copeptin in buffer solns. The dynamic range of the assay in human serum samples also covers the clin. relevant range of the biomarkers. The cross interference in the multiplexed assay is low. These results show the strong potential of the developed GeNPs in multiplexed detection of biomarkers and the developed simple-to-use multiplexed assay in the diagnosis of MI at the point of care.
- 199Shan, J.; Li, X.; Han, S.; Ren, T.; Jin, M.; Wang, X. Gap-enhance Raman tags (GERTs) competitive immunoassay based Raman imaging for the quantitative detection of trace florfenicol in milk. Food Chem. 2022, 391, 133233, DOI: 10.1016/j.foodchem.2022.133233Google ScholarThere is no corresponding record for this reference.
- 200Zhu, S.; Deng, B.; Liu, F.; Li, J.; Lin, L.; Ye, J. Surface-enhanced Raman scattering bioimaging with an ultrahigh signal-to-background ratio under ambient light. ACS Appl. Mater. Interfaces 2022, 14, 8876– 8887, DOI: 10.1021/acsami.2c01063Google ScholarThere is no corresponding record for this reference.
- 201Deng, B.; Wang, Y.; Wu, Y.; Yin, W.; Lu, J.; Ye, J. Raman Nanotags-Guided Intraoperative Sentinel Lymph Nodes Precise Location with Minimal Invasion. Advanced Science 2022, 9, 2102405, DOI: 10.1002/advs.202102405Google ScholarThere is no corresponding record for this reference.
- 202Zhang, Y.; Lin, L.; He, J.; Ye, J. Optical penetration of surface-enhanced micro-scale spatial offset Raman spectroscopy in turbid gel and biological tissue. Journal of Innovative Optical Health Sciences 2021, 14, 2141001, DOI: 10.1142/S1793545821410017Google ScholarThere is no corresponding record for this reference.
- 203Zhang, Y.; Gu, Y.; He, J.; Thackray, B. D.; Ye, J. Ultrabright gap-enhanced Raman tags for high-speed bioimaging. Nat. Commun. 2019, 10, 3905, DOI: 10.1038/s41467-019-11829-yGoogle Scholar203Ultrabright gap-enhanced Raman tags for high-speed bioimagingZhang Yuqing; Gu Yuqing; He Jing; Thackray Benjamin D; Ye Jian; Zhang Yuqing; Ye Jian; Ye JianNature communications (2019), 10 (1), 3905 ISSN:.Surface-enhanced Raman spectroscopy (SERS) is advantageous over fluorescence for bioimaging due to ultra-narrow linewidth of the fingerprint spectrum and weak photo-bleaching effect. However, the existing SERS imaging speed lags far behind practical needs, mainly limited by Raman signals of SERS nanoprobes. In this work, we report ultrabright gap-enhanced Raman tags (GERTs) with strong electromagnetic hot spots from interior sub-nanometer gaps and external petal-like shell structures, larger immobilization surface area, and Raman cross section of reporter molecules. These GERTs reach a Raman enhancement factor beyond 5 × 10(9) and a detection sensitivity down to a single-nanoparticle level. We use a 370 μW laser to realize high-resolution cell imaging within 6 s and high-contrast (a signal-to-background ratio of 80) wide-area (3.2 × 2.8 cm(2)) sentinel lymph node imaging within 52 s. These nanoprobes offer a potential solution to overcome the current bottleneck in the field of SERS-based bioimaging.
- 204Shi, B.; Li, D.; Yao, W.; Wang, W.; Jiang, J.; Wang, R.; Yan, F.; Liu, H.; Zhang, H.; Ye, J. Multifunctional theranostic nanoparticles for multi-modal imaging-guided CAR-T immunotherapy and chemo-photothermal combinational therapy of non-Hodgkin’s lymphoma. Biomaterials Science 2022, 10, 2577– 2589, DOI: 10.1039/D1BM01982AGoogle Scholar204Multifunctional theranostic nanoparticles for multi-modal imaging-guided CAR-T immunotherapy and chemo-photothermal combinational therapy of non-Hodgkins lymphomaShi, Bowen; Li, Dan; Yao, Weiwu; Wang, Wenfang; Jiang, Jiang; Wang, Ruiheng; Yan, Fuhua; Liu, Han; Zhang, Huan; Ye, JianBiomaterials Science (2022), 10 (10), 2577-2589CODEN: BSICCH; ISSN:2047-4849. (Royal Society of Chemistry)Accurate and effective tumor diagnosis, detection, and treatment are key for improving the survival rates of patients. Chimeric antigen receptor T (CAR-T) cell therapy has shown remarkable clin. success in eradicating hematol. malignancies. However, the hostile microenvironment in solid tumors severely prevents CAR-T cells from migrating and from infiltrating and killing malignant cells. Tumor microenvironment modulation strategies have attracted much attention in the field of cancer immunotherapy. Multifunctional nanoplatforms that integrate the advantages of different therapeutic techniques can allow for the multimodal synergistic treatment of tumors. In this study, a biocompatible, tumor-targeting, on-demand approach combining CAR-T cell immunotherapy and a chemo-photothermal therapy nanoplatform (FA-Gd-GERTs@Ibrutinib) based on gadolinium-loaded gap-enhanced Raman tags (Gd-GERTs) has been developed for multimodal imaging, and it provides a reliable treatment strategy for solid tumor immunotherapy via microenvironment reconstruction. In our study, folate (FA) receptor targeted mols. are used to improve the accuracy and sensitivity of computed tomog./magnetic resonance/Raman multimodal tumor imaging. The photothermal effect of the nanoprobe can promote the angiogenesis of lymphoma tissue, destroy the extracellular matrix, loosen compact tissue, stimulate chemokine secretion, and effectively enhance the infiltration ability in the case of non-Hodgkins lymphoma, without dampening the CD19 CAR-T cell activity. The treatment results in tumor-bearing mice proved the existence of excellent synergistic therapy; photothermal therapy improves the accumulation and effector function of CAR-T cells within solid tumors. It is believed that multifunctional nanomaterials with targeted multi-modal imaging capabilities that support combination therapy can provide an efficient route for accurate diagnosis and efficient treatment.
- 205Bao, Z.; Deng, B.; Zhang, Y.; Li, X.; Tan, Z.; Gu, Z.; Gu, B.; Shao, Z.; Di, W.; Ye, J. Ratiometric Raman nanotags enable intraoperative detection of metastatic sentinel lymph node. Biomaterials 2021, 276, 121070, DOI: 10.1016/j.biomaterials.2021.121070Google Scholar205Ratiometric Raman nanotags enable intraoperative detection of metastatic sentinel lymph nodeBao, Zhouzhou; Deng, Binge; Zhang, Yuqing; Li, Xiaowei; Tan, Ziyang; Gu, Zhuowei; Gu, Bobo; Shao, Zhifeng; Di, Wen; Ye, JianBiomaterials (2021), 276 (), 121070CODEN: BIMADU; ISSN:0142-9612. (Elsevier Ltd.)Sentinel lymph node (SLN) imaging and biopsy has been advocated as an important technique to evaluate the metastatic status of regional lymph nodes and det. subsequent surgical procedure for many cancers, yet there is no reliable means to provide accurate and rapid diagnosis of metastatic SLN during surgery. Here we develop a new approach, named "Ratiometric Raman dual-nanotag strategy", that using folic acid functionalized targeted and nontargeted gap-enhanced Raman tags (FA-GERTs and Nt-GERTs) to detect metastatic SLN based on Raman imaging combined with classical least square data processing methods. By using this strategy, with built-in self-calibration for signal correction, rather than abs. intensity-dependent signal readout, we realize the visualization and prompt intraoperative diagnosis of metastatic SLN with a high accuracy of 87.5% when the cut-off value of ratio (FA-GERTs/Nt-GERTs) set at 1.255. This approach may outperform the existing histopathol. assessment in diagnosing SLN metastasis and is promising for guiding surgical procedure in the future.
- 206Shi, B.; Zhang, B.; Zhang, Y.; Gu, Y.; Zheng, C.; Yan, J.; Chen, W.; Yan, F.; Ye, J.; Zhang, H. Multifunctional gap-enhanced Raman tags for preoperative and intraoperative cancer imaging. Acta Biomaterialia 2020, 104, 210– 220, DOI: 10.1016/j.actbio.2020.01.006Google ScholarThere is no corresponding record for this reference.
- 207Kim, M.; Ko, S. M.; Kim, J.-M.; Son, J.; Lee, C.; Rhim, W.-K.; Nam, J.-M. Dealloyed intra-nanogap particles with highly robust, quantifiable surface-enhanced Raman scattering signals for biosensing and bioimaging applications. ACS Central Science 2018, 4, 277– 287, DOI: 10.1021/acscentsci.7b00584Google Scholar207Dealloyed Intra-Nanogap Particles with Highly Robust, Quantifiable Surface-Enhanced Raman Scattering Signals for Biosensing and Bioimaging ApplicationsKim, Minho; Ko, Sung Min; Kim, Jae-Myoung; Son, Jiwoong; Lee, Chungyeon; Rhim, Won-Kyu; Nam, Jwa-MinACS Central Science (2018), 4 (2), 277-287CODEN: ACSCII; ISSN:2374-7951. (American Chemical Society)Uniformly controlling a large no. of metal nanostructures with a plasmonically enhanced signal to generate quant. optical signals and the widespread use of these structures for surface-enhanced Raman scattering (SERS)-based biosensing and bioimaging applications are of paramount importance but are extremely challenging. Here, the authors report a highly controllable, facile selective-interdiffusive dealloying chem. for synthesizing the dealloyed intra-nanogap particles (DIPs) with a ∼ 2 nm intragap in a high yield (∼95%) without the need for an interlayer. The SERS signals from DIPs are highly quant. and polarization-independent with polarized laser sources. Remarkably, all the analyzed particles displayed the SERS enhancement factors (EFs) of ≥1.1 × 108 with a very narrow distribution of EFs. Finally, DIPs can be used as ultrasensitive SERS-based DNA detection probes for detecting 10 aM to 1 pM target concns. and highly robust, quant. real-time cell imaging probes for long-term imaging with low laser power and short exposure time.
- 208Khlebtsov, N. G.; Lin, L.; Khlebtsov, B. N.; Ye, J. Gap-enhanced Raman tags: fabrication, optical properties, and theranostic applications. Theranostics 2020, 10, 2067– 2094, DOI: 10.7150/thno.39968Google Scholar208Gap-enhanced Raman tags: fabrication, optical properties, and theranostic applicationsKhlebtsov, Nikolai G.; Lin, Li; Khlebtsov, Boris N.; Ye, JianTheranostics (2020), 10 (5), 2067-2094CODEN: THERDS; ISSN:1838-7640. (Ivyspring International Publisher)A review. Gap-enhanced Raman tags (GERTs) are emerging probes of surface-enhanced Raman scattering (SERS) spectroscopy that have found promising anal., bioimaging, and theranostic applications. Because of their internal location, Raman reporter mols. are protected from unwanted external environments and particle aggregation and demonstrate superior SERS responses owing to the strongly enhanced electromagnetic fields in the gaps between metal core-shell structures. In this review, we discuss recent progress in the synthesis, simulation, and exptl. studies of the optical properties and biomedical applications of novel spherically sym. and anisotropic GERTs fabricated with common plasmonic metals-gold (Au) and silver (Ag). Our discussion is focused on the design and synthetic strategies that ensure the optimal parameters and highest enhancement factors of GERTs for sensing and theranostics. In particular, we consider various core-shell structures with build-in nanogaps to explain why they would benefit the plasmonic GERTs as a superior SERS tag and how this would help future research in clin. analytics and therapeutics.
- 209Yang, W.; Lim, D.-K. Recent Advances in the Synthesis of Intra-Nanogap Au Plasmonic Nanostructures for Bioanalytical Applications. Adv. Mater. 2020, 32, 2002219, DOI: 10.1002/adma.202002219Google Scholar209Recent Advances in the Synthesis of Intra-Nanogap Au Plasmonic Nanostructures for Bioanalytical ApplicationsYang, Wonseok; Lim, Dong-KwonAdvanced Materials (Weinheim, Germany) (2020), 32 (51), 2002219CODEN: ADVMEW; ISSN:0935-9648. (Wiley-VCH Verlag GmbH & Co. KGaA)Plasmonic nanogap-enhanced Raman scattering has attracted considerable attention in the fields of Raman-based bioanal. applications and materials science. Various strategies have been proposed to prep. nanostructures with an inter- or intra-nanogap for fundamental study models or applications. This report focuses on recent advances in synthetic methods to fabricate intra-nanogap structures with diverse dimensions, with detailed focus on the theory and bioanal. applications. Synthetic strategies ranging from the use of a silica layer to small mols., the use of polymers and galvanic replacement, are extensively investigated. Furthermore, various core structures, such as spherical, rod-, and cube-shaped, are widely studied, and greatly expand the diversity of plasmonic nanostructures with an intra-nanogap. Theor. calcns., ranging from the first plasmonic hybridization model that is applied to a concentric Au-SiO2-Au nanosphere to the modern quantum cor. model, have evolved to accurately describe the plasmonic resonance property in concentric core-shell nanostructures with a subnanometer nanogap. The greatly enhanced and uniform Raman responses from the localized Raman reporter in the built-in nanogap have made it possible to achieve promising probes with an extraordinary high sensitivity in various formats, such as biomol. detection, high-resoln. cell imaging, and an in vivo imaging application.
- 210Lin, L.; Zapata, M.; Xiong, M.; Liu, Z.; Wang, S.; Xu, H.; Borisov, A. G.; Gu, H.; Nordlander, P.; Aizpurua, J.; Ye, J. Nanooptics of plasmonic nanomatryoshkas: shrinking the size of a core–shell junction to subnanometer. Nano Lett. 2015, 15, 6419– 6428, DOI: 10.1021/acs.nanolett.5b02931Google Scholar210Nanooptics of Plasmonic Nanomatryoshkas: Shrinking the Size of a Core-Shell Junction to SubnanometerLin, Li; Zapata, Mario; Xiong, Min; Liu, Zhonghui; Wang, Shanshan; Xu, Hong; Borisov, Andrei G.; Gu, Hongchen; Nordlander, Peter; Aizpurua, Javier; Ye, JianNano Letters (2015), 15 (10), 6419-6428CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)Quantum effects in plasmonic systems play an important role in defining the optical response of structures with subnanometer gaps. Electron tunneling across the gaps can occur, altering both the far-field optical response and the near-field confinement and enhancement. Plasmon coupling in Au nanomatryoshka (NM) nanoparticles with different core-shell sepns. were exptl. and theor. studied. Plasmon coupling effects between the core and the shell become significant when their sepn. decreases to 15 nm. When their sepn. decreases to <1 nm, the near- and far-field properties can no longer be described by classical approaches but require the inclusion of quantum mech. effects such as electron transport through the self-assembled monolayer of mol. junction. Surface-enhanced Raman scattering measurements indicate strong electron transport-induced charge transfer across the mol. junction. The quantum modeling provides an est. for the a.c. conductances of mols. in the junction. The insights acquired from this work pave the way for the development of novel quantum plasmonic devices and substrates for surface-enhanced Raman scattering.
- 211Lin, L.; Zhang, Q.; Li, X.; Qiu, M.; Jiang, X.; Jin, W.; Gu, H.; Lei, D. Y.; Ye, J. Electron Transport Across Plasmonic Molecular Nanogaps Interrogated with Surface-Enhanced Raman Scattering. ACS Nano 2018, 12, 6492– 6503, DOI: 10.1021/acsnano.7b08224Google Scholar211Electron Transport Across Plasmonic Molecular Nanogaps Interrogated with Surface-Enhanced Raman ScatteringLin, Li; Zhang, Qiang; Li, Xiyao; Qiu, Meng; Jiang, Xin; Jin, Wei; Gu, Hongchen; Lei, Dang Yuan; Ye, JianACS Nano (2018), 12 (7), 6492-6503CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Charge transport plays an important role in defining both far-field and near-field optical response of a plasmonic nanostructure with an ultrasmall built-in nanogap. As the gap size of a Au core-shell nanomatryoshka approaches the sub-nanometer length scale, charge transport may occur and strongly alter the near-field enhancement within the mol.-filled nanogap. Ultrasensitive surface-enhanced Raman spectroscopy (SERS) was used to study the plasmonic near-field variation induced by the mol. junction conductance-assisted electron transport in Au nanomatryoshkas, termed gap-enhanced Raman tags (GERTs). The GERTs, with interior gaps from 0.7 to 2 nm, are prepd. with a wet chem. method. The exptl. and theor. studies suggest that the electron transport through the mol. junction influences both far-field and near-field optical properties of the GERTs. In the far-field extinction response, the low-energy gap mode predicted by a classical electromagnetic model (CEM) is strongly quenched and hence unobservable in the expt., which can be well explained by a quantum-cor. model (QCM). In the near-field SERS response, the optimal gap size for max. Raman enhancement at the excitation wavelength of 785 nm (633 nm) is ∼1.35 nm (1.8 nm). Similarly, these near-field results do not tally with the CEM calcns. but agree well with the QCM results where the mol. junction conductance in the nanogap is fully considered. The study may improve understanding of charge-transport phenomena in ultrasmall plasmonic mol. nanogaps and promote the further development of mol. electronics-based plasmonic nanodevices.
- 212Lin, L.; Ji, W.; Zhang, L.-W.; Ye, J. Atomic Insights into the Evolution of Three-Dimensional Molecular Junctions in Plasmonic Core–Shell Nanoparticles. J. Phys. Chem. C 2021, 125, 1865– 1873, DOI: 10.1021/acs.jpcc.0c09552Google ScholarThere is no corresponding record for this reference.
- 213Li, J.; Liu, F.; He, C.; Shen, F.; Ye, J. Orthogonal gap-enhanced Raman tags for interference-free and ultrastable surface-enhanced Raman scattering. Nanophotonics 2022, 11, 1549– 1560, DOI: 10.1515/nanoph-2021-0689Google Scholar213Orthogonal gap-enhanced Raman tags for interference-free and ultrastable surface-enhanced Raman scatteringLi, Jin; Liu, Fugang; He, Chang; Shen, Feng; Ye, JianNanophotonics (2022), 11 (8), 1549-1560CODEN: NANOLP; ISSN:2192-8614. (Walter de Gruyter GmbH)Spectral interference from backgrounds is not negligible for surface-enhanced Raman scattering (SERS) tags and often influences the accuracy and reliability of SERS applications. We report the design and synthesis of orthogonal gap-enhanced Raman tags (O-GERTs) by embedding alkyne and deuterium-based reporters in the interior metallic nanogaps of core-shell nanoparticles and explore their signal orthogonality as optical probes against different backgrounds from common substrates and media (e.g., glass and polymer) to related targets (e.g., bacteria, cancer cells, and tissues). Proof-of-concept expts. show that the O-GERT signals in the fingerprint region (200-1800 cm-1) are likely interfered by various backgrounds, leading to difficulty of accurate quantification, while the silent-region (1800-2800 cm-1) signals are completely interference-free. Moreover, O-GERTs show much higher photo and biol. stability compared to conventional SERS tags. This work not only demonstrates O-GERTs as universal optical tags for accurate and reliable detection onto various substrates and in complex media, but also opens new opportunities in a variety of frontier applications, such as three-dimensional data storage and security labeling.
- 214Fan, S.; Scarpitti, B. T.; Luo, Z.; Smith, A. E.; Ye, J.; Schultz, Z. D. Facile synthesis of intra-nanogap enhanced Raman tags with different shapes. Nano Research 2024, 17, 8415– 8423, DOI: 10.1007/s12274-024-6807-yGoogle ScholarThere is no corresponding record for this reference.
- 215Shen, J.; Jiang, X.; Xu, L.; Ge, Z.; Li, Q.; Song, B.; Wang, L.; Song, S. Poly-Adenine-Engineered Gold Nanogaps for SERS Nanostructures. ACS Applied Nano Materials 2019, 2, 3501– 3509, DOI: 10.1021/acsanm.9b00473Google Scholar215Poly-Adenine-Engineered Gold Nanogaps for SERS NanostructuresShen, Jianlei; Jiang, Xiankai; Xu, Lifeng; Ge, Zhilei; Li, Qian; Song, Bo; Wang, Lihua; Song, ShipingACS Applied Nano Materials (2019), 2 (6), 3501-3509CODEN: AANMF6; ISSN:2574-0970. (American Chemical Society)Surface-enhanced Raman scattering (SERS) effect, usually is assocd. with the highly confined electromagnetic field in plasmonic nanostructures, and has been widely investigated for mol. sensing and imaging applications. However, SERS substrates have confronted with poor reproducibility and inefficient nanometer-level structural control. By employing oligonucleotides, highly reproducible SERS substrates with uniform 1 nm nanogap could be constructed. In this work, we investigated the effect of oligonucleotides, esp. the unmodified oligonucleotides, on the morphol. of nanogaps. We found that the morphol. of nanogap is dependent on the sequence, length, and surface-coating d. of the unmodified oligonucleotide and speculate that the formation of nanogaps is dominated by stable self-assembled monolayers (SAMs) of unmodified oligonucleotides, which is supported by mol. dynamic simulation (MD) results. We further studied the morphologies of nanogaps, with oligonucleotide SAMs of different states and nanoseeds of different sizes and shapes. This work elucidated the relationships between the SAMs of unmodified oligonucleotides and the morphol. of nanogaps, which will facilitate the design of reliable SERS nanostructures.
- 216Kim, J.-M.; Kim, J.; Choi, K.; Nam, J.-M. Plasmonic Dual-Gap Nanodumbbells for Label-Free On-Particle Raman DNA Assays. Adv. Mater. 2023, 35, 2208250, DOI: 10.1002/adma.202208250Google ScholarThere is no corresponding record for this reference.
- 217Acapulco, J. A. I.; Hong, S.; Kim, S. K.; Park, S. Controlling optical properties of metallic multi-shell nanoparticles through suppressed surface plasmon resonance. J. Colloid Interface Sci. 2016, 461, 376– 382, DOI: 10.1016/j.jcis.2015.09.040Google ScholarThere is no corresponding record for this reference.
- 218Lin, L.; He, H.; Xue, R.; Zhang, Y.; Wang, Z.; Nie, S.; Ye, J. Direct and quantitative assessments of near-infrared light attenuation and spectroscopic detection depth in biological tissues using surface-enhanced Raman scattering. Med-X 2023, 1, 9, DOI: 10.1007/s44258-023-00010-2Google ScholarThere is no corresponding record for this reference.
- 219Khlebtsov, B. N.; Burov, A. M.; Bratashov, D. N.; Tumskiy, R. S.; Khlebtsov, N. G. Petal-like Gap-Enhanced Raman Tags with Controllable Structures for High-Speed Raman Imaging. Langmuir 2020, 36, 5546– 5553, DOI: 10.1021/acs.langmuir.0c00623Google Scholar219Petal-like Gap-Enhanced Raman Tags with Controllable Structures for High-Speed Raman ImagingKhlebtsov, Boris N.; Burov, Andrey M.; Bratashov, Daniil N.; Tumskiy, Roman S.; Khlebtsov, Nikolai G.Langmuir (2020), 36 (20), 5546-5553CODEN: LANGD5; ISSN:0743-7463. (American Chemical Society)Surface-enhanced Raman scattering (SERS) is widely used for in vitro and in vivo bioimaging applications. However, reproducible and controllable fabrication of SERS tags with high d. of electromagnetic hot-spots is still challenging. We report an improved strategy for the synthesis of core/shell Raman tags with high d. of hot-spots and high immobilization of reporter mols. The strategy is based on simultaneous growth and functionalization of an Au shell around Au nanospheres coated with 4-nitrobenzenethiol (NBT). The amt. of added 4-NBT is key factor to control the structure SERS response of the resulting particles. Specifically, we demonstrate the formation of gap-enhanced Raman tags (GERTs) with a smooth solid shell (sGERTs), petal-like GERTs (pGERTs), and mesoporous Au particles (mGERTs) filled with Raman mols. In contrast to NBT mols., similar thiols such as 1,4-benzenedithiol (BDT) and 2-naphtalenethiol (NT) do not support the formation of pGERTs and mGERTs. To explain this finding, we proposed a growth mechanism based on the unique chem. structure of NBT. The SERS response of optimized pGERTs is 50 times higher than that from usual sGERTs, which makes pGERTs suitable for single-particle spectroscopy. We demonstrate successful application of pGERTs for high-speed cell imaging using 10 ms accumulation time per pixel and a total imaging time of about 1 min. Because of the high SERS response and unique porous structure, these nanoparticles have great potential for bioimaging and other applications.
- 220Chen, M.; Zhao, X.; Wang, B.; Liu, H.; Chen, Z.; Sun, L.; Xu, X. Graphene-wrapped petal-like gap-enhanced Raman tags for enhancing photothermal conversion and Raman imaging. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 2024, 304, 123306, DOI: 10.1016/j.saa.2023.123306Google ScholarThere is no corresponding record for this reference.
- 221Zhang, M.; Xu, S.; Guan, P.-C.; Zhang, Y.-J.; Li, J.-F. Application of Gap Mode Ultrasensitive P-GERTs in SERS-Based Rapid Detection. Photonics 2024, 11, 708, DOI: 10.3390/photonics11080708Google ScholarThere is no corresponding record for this reference.
- 222Lee, J. H.; Oh, J. W.; Nam, S. H.; Cha, Y. S.; Kim, G. H.; Rhim, W. K.; Kim, N. H.; Kim, J.; Han, S. W.; Suh, Y. D.; Nam, J. M. Synthesis, Optical Properties, and Multiplexed Raman Bio-Imaging of Surface Roughness-Controlled Nanobridged Nanogap Particles. Small 2016, 12, 4726– 34, DOI: 10.1002/smll.201600289Google Scholar222Synthesis, Optical Properties, and Multiplexed Raman Bio-Imaging of Surface Roughness-Controlled Nanobridged Nanogap ParticlesLee, Jung-Hoon; Oh, Jeong-Wook; Nam, Sang Hwan; Cha, Yeong Seok; Kim, Gyeong-Hwan; Rhim, Won-Kyu; Kim, Nam Hoon; Kim, Jongwoo; Han, Sang Woo; Suh, Yung Doug; Nam, Jwa-MinSmall (2016), 12 (34), 4726-4734CODEN: SMALBC; ISSN:1613-6810. (Wiley-VCH Verlag GmbH & Co. KGaA)Plasmonic nanostructures are widely studied and used because of their useful size, shape, compn. and assembled structure-based plasmonic properties. It is, however, highly challenging to precisely design, reproducibly synthesize and reliably utilize plasmonic nanostructures with enhanced optical properties. Here, we devise a facile synthetic method to generate Au surface roughness-controlled nanobridged nanogap particles (Au-RNNPs) with ultrasmall (≈1 nm) interior gap and tunable surface roughness in a highly controllable manner. Importantly, we found that particle surface roughness can be assocd. with and enhance the electromagnetic field inside the interior gap, and stronger nanogap-enhanced Raman scattering (NERS) signals can be generated from particles by increasing particle surface roughness. The finite-element method-based calcn. results support and are matched well with the exptl. results and suggest one needs to consider particle shape, nanogap and nanobridges simultaneously to understand and control the optical properties of this type of nanostructures. Finally, the potential of multiplexed Raman detection and imaging with RNNPs and the high-speed, high-resoln. Raman bio-imaging of Au-RNNPs inside cells with a wide-field Raman imaging setup with liq. crystal tunable filter are demonstrated. Our results provide strategies and principles in designing and synthesizing plasmonically enhanced nanostructures and show potential for detecting and imaging Raman nanoprobes in a highly specific, sensitive and multiplexed manner.
- 223Chen, S.; Fan, J.; Lv, M.; Hua, C.; Liang, G.; Zhang, S. Internal Standard Assisted Surface-Enhanced Raman Scattering Nanoprobe with 4-NTP as Recognition Unit for Ratiometric Imaging Hydrogen Sulfide in Living Cells. Anal. Chem. 2022, 94, 14675– 14681, DOI: 10.1021/acs.analchem.2c02961Google ScholarThere is no corresponding record for this reference.
- 224Zhang, W.; Rahmani, M.; Niu, W.; Ravaine, S.; Hong, M.; Lu, X. Tuning Interior Nanogaps of Double-shelled Au/Ag Nanoboxes for Surface-Enhanced Raman Scattering. Sci. Rep. 2015, 5, 8382, DOI: 10.1038/srep08382Google Scholar224Tuning Interior Nanogaps of Double-shelled Au/Ag Nanoboxes for Surface-Enhanced Raman ScatteringZhang, Weiqing; Rahmani, Mohsen; Niu, Wenxin; Ravaine, Serge; Hong, Minghui; Lu, XianmaoScientific Reports (2015), 5 (), 8382CODEN: SRCEC3; ISSN:2045-2322. (Nature Publishing Group)Double-shelled Au/Ag hollow nanoboxes with precisely controlled interior nanogaps (1 to 16 nm) were synthesized for gap-tunable surface-enhanced Raman scattering (SERS). The double-shelled nanoboxes were prepd. via a two-step galvanic replacement reaction approach using Ag nanocubes as the templates, while 4-aminothiolphenol (4-ATP) as SERS probe mols. were loaded between the two shells. More than 10-fold enhancement of SERS is obsd. from the double-shelled nanoboxes than Ag nanocubes. In addn., the SERS of the double-shelled nanoboxes increase significantly with the decrease of gap size, consistent with the theor. prediction that smaller gap size induces larger localized electromagnetic enhancement.
- 225Jin, X.; Khlebtsov, B. N.; Khanadeev, V. A.; Khlebtsov, N. G.; Ye, J. Rational Design of Ultrabright SERS Probes with Embedded Reporters for Bioimaging and Photothermal Therapy. ACS Appl. Mater. Interfaces 2017, 9, 30387– 30397, DOI: 10.1021/acsami.7b08733Google Scholar225Rational Design of Ultrabright SERS Probes with Embedded Reporters for Bioimaging and Photothermal TherapyJin, Xiulong; Khlebtsov, Boris N.; Khanadeev, Vitaly A.; Khlebtsov, Nikolai G.; Ye, JianACS Applied Materials & Interfaces (2017), 9 (36), 30387-30397CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Plasmonic nanoparticles can be utilized as surface-enhanced Raman scattering (SERS) probes for bioimaging and as photothermal (PT) agents for cancer therapy. Typically, their SERS and PT efficiencies reach maximal values under the on-resonant condition, when the excitation wavelength overlaps the localized surface plasmon resonance (LSPR) wavelength preferably in the near-IR (NIR) biol. window. However, the photogenerated heat may inevitably disturb or even destroy biol. samples during the imaging process. Herein, the authors develop ultrabright SERS probes composed of metallic Au@Ag core-shell rodlike nanomatryoshkas (RNMs) with embedded Raman reporters. By rationally controlling the Ag shell thickness, the LSPR of RNMs can be tuned from UV to NIR range, resulting in highly tunable SERS and PT properties. As bright NIR SERS imaging nanoprobes, RNMs with a thick Ag shell are designed for minimal PT damage to the biol. targets under the off-resonance condition, as illustrated through monitoring the changes in mitochondrial membrane potential of cancer cells during SERS imaging procedure. By contrast, RNMs with a thin Ag shell are designed as multifunctional NIR theranostic probes that combine enhanced photothermal therapy capability, as exemplified by efficient PT killing of cancer cells, with reduced yet still efficient imaging properties at the on-resonance excitation.
- 226Zhang, Y.; Chen, R.; Liu, F.; Miao, P.; Lin, L.; Ye, J. In Vivo Surface-Enhanced Transmission Raman Spectroscopy under Maximum Permissible Exposure: Toward Photosafe Detection of Deep-Seated Tumors. Small Methods 2023, 7, 2201334, DOI: 10.1002/smtd.202201334Google ScholarThere is no corresponding record for this reference.
- 227Prodan, E.; Radloff, C.; Halas, N. J.; Nordlander, P. A hybridization model for the plasmon response of complex nanostructures. Science 2003, 302, 419– 22, DOI: 10.1126/science.1089171Google Scholar227A hybridization model for the plasmon response of complex nanostructuresProdan, E.; Radloff, C.; Halas, N. J.; Nordlander, P.Science (Washington, DC, United States) (2003), 302 (5644), 419-422CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)The authors present a simple and intuitive picture, an electromagnetic analog of MO theory, that describes the plasmon response of complex nanostructures of arbitrary shape. The authors' model can be understood as the interaction or hybridization of elementary plasmons supported by nanostructures of elementary geometries. As an example, the approach is applied to the important case of a four-layer concentric nanoshell, where the hybridization of the plasmons of the inner and outer nanoshells dets. the resonant frequencies of the multilayer nanostructure.
- 228Savage, K. J.; Hawkeye, M. M.; Esteban, R.; Borisov, A. G.; Aizpurua, J.; Baumberg, J. J. Revealing the quantum regime in tunnelling plasmonics. Nature 2012, 491, 574– 7, DOI: 10.1038/nature11653Google Scholar228Revealing the quantum regime in tunnelling plasmonicsSavage, Kevin J.; Hawkeye, Matthew M.; Esteban, Ruben; Borisov, Andrei G.; Aizpurua, Javier; Baumberg, Jeremy J.Nature (London, United Kingdom) (2012), 491 (7425), 574-577CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)When 2 metal nanostructures are placed nanometers apart, their optically driven free electrons couple elec. across the gap. The resulting plasmons have enhanced optical fields of a specific color tightly confined inside the gap. Many emerging nanophotonic technologies depend on the careful control of this plasmonic coupling, including optical nanoantennas for high-sensitivity chem. and biol. sensors, nanoscale control of active devices, and improved photovoltaic devices. But for subnanometre gaps, coherent quantum tunnelling becomes possible and the system enters a regime of extreme nonlocality in which previous classical treatments fail. Electron correlations across the gap that are driven by quantum tunnelling require a new description of nonlocal transport, which is crucial in nanoscale optoelectronics and single-mol. electronics. Here, by simultaneously measuring both the elec. and optical properties of 2 Au nanostructures with controllable subnanometre sepn., the authors reveal the quantum regime of tunnelling plasmonics in unprecedented detail. All obsd. phenomena are in good agreement with recent quantum-based models of plasmonic systems, which eliminate the singularities predicted by classical theories. These findings imply that tunnelling establishes a quantum limit for plasmonic field confinement of ∼10-8λ3 for visible light (of wavelength λ). Work thus prompts new theor. and exptl. studies into quantum-domain plasmonic systems, and will affect the future of nanoplasmonic device engineering and nanoscale photochem.
- 229Song, Z.-L.; Chen, Z.; Bian, X.; Zhou, L.-Y.; Ding, D.; Liang, H.; Zou, Y.-X.; Wang, S.-S.; Chen, L.; Yang, C.; Zhang, X.-B.; Tan, W. Alkyne-Functionalized Superstable Graphitic Silver Nanoparticles for Raman Imaging. J. Am. Chem. Soc. 2014, 136, 13558– 13561, DOI: 10.1021/ja507368zGoogle Scholar229Alkyne-Functionalized Superstable Graphitic Silver Nanoparticles for Raman ImagingSong, Zhi-Ling; Chen, Zhuo; Bian, Xia; Zhou, Li-Yi; Ding, Ding; Liang, Hao; Zou, Yu-Xiu; Wang, Shan-Shan; Chen, Long; Yang, Chao; Zhang, Xiao-Bing; Tan, WeihongJournal of the American Chemical Society (2014), 136 (39), 13558-13561CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Noble metals, esp. gold, have been widely used in plasmon resonance applications. Although silver has a larger optical cross section and lower cost than gold, it has attracted much less attention because of its easy corrosion, thereby degrading plasmonic signals and limiting its applications. To circumvent this problem, the authors report the facile synthesis of superstable AgCu@graphene (ACG) nanoparticles (NPs). The growth of several layers of graphene onto the surface of AgCu alloy NPs effectively protects the Ag surface from contamination, even in the presence of hydrogen peroxide, hydrogen sulfide, and nitric acid. The ACG NPs have been used to enhance the unique Raman signals from the graphitic shell, making ACG an ideal candidate for cell labeling, rapid Raman imaging, and SERS detection. ACG is further functionalized with alkyne-polyethylene glycol, which has strong Raman vibrations in the Raman-silent region of the cell, leading to more accurate colocalization inside cells. In sum, this work provides a simple approach to fabricate corrosion-resistant, water-sol., and graphene-protected AgCu NPs having a strong surface plasmon resonance effect suitable for sensing and imaging.
- 230Palla, M.; Kumar, S.; Li, Z.; Jockusch, S.; Russo, J. J.; Ju, J.; Bosco, F. G.; Rindzevicius, T.; Alstrom, T. S.; Schmidt, M. S.; Boisen, A. Click chemistry based biomolecular conjugation monitoring using surface-enhanced Raman spectroscopy mapping; IEEE SENSORS , 30 Oct.–3 Nov. 2016; pp 1– 3. DOI: 10.1109/ICSENS.2016.7808595 .Google ScholarThere is no corresponding record for this reference.
- 231Kong, K. V.; Lam, Z.; Goh, W. D.; Leong, W. K.; Olivo, M. Metal Carbonyl-Gold Nanoparticle Conjugates for Live-Cell SERS Imaging. Angew. Chem. Int. Edit 2012, 51, 9796– 9799, DOI: 10.1002/anie.201204349Google Scholar231Metal Carbonyl-Gold Nanoparticle Conjugates for Live-Cell SERS ImagingKong, Kien Voon; Lam, Zhiyong; Goh, Wenda Douglas; Leong, Weng Kee; Olivo, MaliniAngewandte Chemie, International Edition (2012), 51 (39), 9796-9799, S9796/1-S9796/7CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)A novel metal carbonyl-based biotag has been prepd. by combining osmium carbonyl clusters and gold nanoparticles, as an example of an organometallic-nanoparticle (OM-NP) conjugate. These OM-NP conjugates display excellent aq. dispersibility and storage stability. Furthermore, they can be readily functionalized with suitable binding ligands to produce biol. functional OM-NP-L conjugates, which the authors have demonstrated in live-cell imaging. It shows clearly the advantage of transition-metal carbonyl compds., for which the CO stretching vibration signal is well-sepd. from other mol. vibrational modes of the cell, in live-cell imaging. In addn., in comparison to the other detection modes, the authors' approach offers both greater sensitivity (signal strength and signal-to-noise) and good spatial resoln.
- 232Stiles, P. L.; Dieringer, J. A.; Shah, N. C.; Van Duyne, R. P. Surface-enhanced Raman spectroscopy. Annu. Rev. Anal Chem. (Palo Alto Calif) 2008, 1, 601– 26, DOI: 10.1146/annurev.anchem.1.031207.112814Google Scholar232Surface-enhanced Raman spectroscopyStiles Paul L; Dieringer Jon A; Shah Nilam C; Van Duyne Richard PAnnual review of analytical chemistry (Palo Alto, Calif.) (2008), 1 (), 601-26 ISSN:.The ability to control the size, shape, and material of a surface has reinvigorated the field of surface-enhanced Raman spectroscopy (SERS). Because excitation of the localized surface plasmon resonance of a nanostructured surface or nanoparticle lies at the heart of SERS, the ability to reliably control the surface characteristics has taken SERS from an interesting surface phenomenon to a rapidly developing analytical tool. This article first explains many fundamental features of SERS and then describes the use of nanosphere lithography for the fabrication of highly reproducible and robust SERS substrates. In particular, we review metal film over nanosphere surfaces as excellent candidates for several experiments that were once impossible with more primitive SERS substrates (e.g., metal island films). The article also describes progress in applying SERS to the detection of chemical warfare agents and several biological molecules.
- 233Shao, F.; Lu, Z.; Liu, C.; Han, H.; Chen, K.; Li, W.; He, Q.; Peng, H.; Chen, J. Hierarchical Nanogaps within Bioscaffold Arrays as a High-Performance SERS Substrate for Animal Virus Biosensing. Acs Appl. Mater. Inter 2014, 6, 6281– 6289, DOI: 10.1021/am4045212Google Scholar233Hierarchical Nanogaps within Bioscaffold Arrays as a High-Performance SERS Substrate for Animal Virus BiosensingShao, Feng; Lu, Zhicheng; Liu, Chen; Han, Heyou; Chen, Kun; Li, Wentao; He, Qigai; Peng, Hui; Chen, JuanniACS Applied Materials & Interfaces (2014), 6 (9), 6281-6289CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)A three-dimensional (3D) biomimetic SERS substrate with hierarchical nanogaps was formed on the bioscaffold arrays of cicada wings by one-step and reagents-free ion-sputtering techniques. This approach requires a minimal fabrication effort and cost and offers Ag nanoislands and Ag nanoflowers with four types of nanogaps (<10 nm) on the chitin nanopillars to generate a high d. of hotspots (∼2000/μm2). The 3D biomimetic substrate shows a low detection limit to Rhodamine 6G (10-13 M), high av. enhancement factor (EF, 5.8 × 107), excellent signal uniformity (5.4%), good stability, and suitability in biosensing. Furthermore, the finite-difference time-domain (FDTD) elec.-field-distribution simulations illustrate that the 3D biomimetic SERS substrate provides the high-d. hotspot area within a detection vol., resulting in enormous SERS enhancement. In addn., the conspicuous far-field plasmon resonance peaks were not found to be a strong requirement for a high EF in 3D biomimetic substrates. Addnl., the novel substrate was applied in label-free animal viruses detection and differentiation with small amts. (1.0 μL) and low concns. of analyte (1 × 103 PFU/mL), and it exhibited potential as an effective SERS platform for virus detection and sensing.
- 234Liu, H.-L.; Cao, J.; Hanif, S.; Yuan, C.; Pang, J.; Levicky, R.; Xia, X.-H.; Wang, K. Size-Controllable Gold Nanopores with High SERS Activity. Anal. Chem. 2017, 89, 10407– 10413, DOI: 10.1021/acs.analchem.7b02410Google Scholar234Size-Controllable Gold Nanopores with High SERS ActivityLiu, Hai-Ling; Cao, Jiao; Hanif, Sumaira; Yuan, Chunge; Pang, Jie; Levicky, Rastislav; Xia, Xing-Hua; Wang, KangAnalytical Chemistry (Washington, DC, United States) (2017), 89 (19), 10407-10413CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Nanopore structures have been successfully employed in next-generation DNA sequencing. For more complicated protein which normally contains 20 different amino acids, identifying the fluctuation of ionic current caused by different amino acids appears inadequate for protein sequencing. Therefore, it is highly desirable to develop size-controllable nanopores with optical activity that can provide addnl. structural information. Herein, the authors discovered the novel nanopore properties of the self-assembled ultramicroelectrodes originally developed by Bard and coworkers. Using a slightly modified method, the self-assembly of 7±1 nm gold nanoparticles (AuNPs) can be precisely controlled to form a gold nanoporous sphere (GPS) on the tip of a glass capillary. Different dithiol linker mols. (1,3-propanedithiol, C3; 1,6-hexanedithiol, C6; and 1,9-nonanedithiol, C9) reproducibly led to rather similar nanopore sizes (5.07±0.02, 5.13±0.02, and 5.25±0.01 nm), resp. The GPS nanostructures were found to exhibit high ionic current rectification as well as surface-enhanced Raman scattering (SERS) activity due to the presence of nanopores and numerous "hot spots" among the crosslinked AuNPs on the surface of GPS. The rectification effect of the small nanopores was obsd. even under high concn. of electrolyte (290 mM), along with SERS enhancement factors well above 1 × 105. The GPS nanostructures were successfully applied for SERS-based detection of glutathione from a single HeLa cell.
- 235Martin, L. C.; Larmour, I. A.; Faulds, K.; Graham, D. Turning up the lights─fabrication of brighter SERRS nanotags. Chem. Commun. 2010, 46, 5247– 5249, DOI: 10.1039/c0cc00722fGoogle ScholarThere is no corresponding record for this reference.
- 236Huang, Y.; Swarup, V. P.; Bishnoi, S. W. Rapid Raman Imaging of Stable, Functionalized Nanoshells in Mammalian Cell Cultures. Nano Lett. 2009, 9, 2914– 2920, DOI: 10.1021/nl901234xGoogle Scholar236Rapid Raman Imaging of Stable, Functionalized Nanoshells in Mammalian Cell CulturesHuang, Yiming; Swarup, Vimal P.; Bishnoi, Sandra WhaleyNano Letters (2009), 9 (8), 2914-2920CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)Two Raman-active poly(ethylene glycol) (PEG) mols., one linear (MW 5000) and the other branched (MW 2420), are synthesized to stabilize gold-silica nanoshells in cell culture media and track nanoparticles in mammalian cell cultures. The linear PEG provides greater nanoshell stability in saline soln. compared to com. available PEG-thiol or the branched PEG. Surface enhanced Raman scattering rapidly tracks the probes and provides semiquant. information regarding particle localization within mouse macrophage (RAW 264.7) and human breast cancer (MCF 7) cell cultures.
- 237Kneipp, K.; Kneipp, H.; Itzkan, I.; Dasari, R. R.; Feld, M. S. Ultrasensitive Chemical Analysis by Raman Spectroscopy. Chem. Rev. 1999, 99, 2957– 2976, DOI: 10.1021/cr980133rGoogle Scholar237Ultrasensitive chemical analysis by Raman spectroscopyKneipp, Katrin; Kneipp, Harald; Itzkan, Irving; Dasari, Ramachandra R.; Feld, Michael S.Chemical Reviews (Washington, D. C.) (1999), 99 (10), 2957-2975CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review with 133 refs. is given on surface-enhanced Raman scattering, single-mol. Raman spectroscopy, crit. anal. and prospects of single-mol. Raman spectroscopy.
- 238McNay, G.; Eustace, D.; Smith, W. E.; Faulds, K.; Graham, D. Surface-Enhanced Raman Scattering (SERS) and Surface-Enhanced Resonance Raman Scattering (SERRS): A Review of Applications. Appl. Spectrosc. 2011, 65, 825– 837, DOI: 10.1366/11-06365Google Scholar238Surface-enhanced Raman scattering (SERS) and surface-enhanced resonance Raman scattering (SERRS): a review of applicationsMcNay, Graeme; Eustace, David; Smith, W. Ewen; Faulds, Karen; Graham, DuncanApplied Spectroscopy (2011), 65 (8), 825-837CODEN: APSPA4; ISSN:0003-7028. (Society for Applied Spectroscopy)A review. Surface-enhanced Raman scattering (SERS) and surface-enhanced resonance Raman scattering (SERRS) can provide pos. identification of an analyte or an analyte mixt. with high sensitivity and selectivity. Better understanding of the theory and advances in the understanding of the practice have led to the development of practical applications in which the unique advantages of SERS/SERRS have been used to provide effective solns. to difficult anal. problems. This review presents a basic theory and illustrates the way in which SERS/SERRS has been developed for practical use.
- 239Chen, Y.; Ren, J.-Q.; Zhang, X.-G.; Wu, D.-Y.; Shen, A.-G.; Hu, J.-M. Alkyne-modulated surface-enhanced Raman scattering-palette for optical interference-free and multiplex cellular imaging. Anal. Chem. 2016, 88, 6115– 6119, DOI: 10.1021/acs.analchem.6b01374Google Scholar239Alkyne-Modulated Surface-Enhanced Raman Scattering-Palette for Optical Interference-Free and Multiplex Cellular ImagingChen, Yong; Ren, Jia-Qiang; Zhang, Xia-Guang; Wu, De-Yin; Shen, Ai-Guo; Hu, Ji-MingAnalytical Chemistry (Washington, DC, United States) (2016), 88 (12), 6115-6119CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)The alkyne tags possess unique interference-free Raman emissions but are still hindered for further application in the field of biochem. labels due to its extremely weak spontaneous Raman scattering. With the aid of computational chem., herein, an alkyne-modulated surface-enhanced Raman scattering (SERS) palette is constructed based on rationally designed 4-ethynylbenzenethiol derivs. for spectroscopic signature, Au@Ag core for optical enhancement and an encapsulating polyallylamine shell for protection and conjugation. Even for the pigment rich plant cell (e.g., pollen), the alkyne-coded SERS tag can be highly discerned on two-dimension distribution impervious to strong org. interferences originating from resonance-enhanced Raman scattering or autofluorescence. In addn., the alkynyl-contg. Raman reporters contribute esp. narrow emission, band shift-tunable (2100-2300 cm-1) and tremendously enhanced Raman signals when the alkynyl group locates at para position of mercaptobenzene ring. Depending on only single Raman band, the suggested alkyne-modulated SERS-palette potentially provides a more effective soln. for multiplex cellular imaging with vibrant colors, when the hyperspectral and fairly intense optical noises originating from lower wavenumber region (<1800 cm-1) are inevitable under complex ambient conditions.
- 240Zeng, Y.; Ren, J.-Q.; Shen, A.-G.; Hu, J.-M. Splicing Nanoparticles-Based “Click” SERS Could Aid Multiplex Liquid Biopsy and Accurate Cellular Imaging. J. Am. Chem. Soc. 2018, 140, 10649– 10652, DOI: 10.1021/jacs.8b04892Google Scholar240Splicing Nanoparticles-Based "Click" SERS Could Aid Multiplex Liquid Biopsy and Accurate Cellular ImagingZeng, Yi; Ren, Jia-Qiang; Shen, Ai-Guo; Hu, Ji-MingJournal of the American Chemical Society (2018), 140 (34), 10649-10652CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Here, a completely new readout technique, so-called "Click" SERS, has been developed based on Raman scattered light splice derived from nanoparticle (NP) assemblies. The single and narrow (1-2 nm) emission originating from triple bond-contg. reporters undergoes dynamic combinatorial output, by controllable splice of SERS-active NPs analogous to small mol. units in click chem. Entirely different to conventional "sole code related to sole target" readout protocol, the intuitional, predictable and uniquely identifiable "Click" SERS is relies on the no. rather than the intensity of combinatorial emissions. By this technique, 10-plex synchronous biomarkers detection under a single scan, and accurate cellular imaging under double exposure have been achieved. "Click" SERS demonstrated multiple single band Raman scattering could be an authentic optical anal. method in biomedicine.
- 241Bai, X.-R.; Wang, L.-H.; Ren, J.-Q.; Bai, X.-W.; Zeng, L.-W.; Shen, A.-G.; Hu, J.-M. Accurate Clinical Diagnosis of Liver Cancer Based on Simultaneous Detection of Ternary Specific Antigens by Magnetic Induced Mixing Surface-Enhanced Raman Scattering Emissions. Anal. Chem. 2019, 91, 2955– 2963, DOI: 10.1021/acs.analchem.8b05153Google Scholar241Accurate Clinical Diagnosis of Liver Cancer Based on Simultaneous Detection of Ternary Specific Antigens by Magnetic Induced Mixing Surface-Enhanced Raman Scattering EmissionsBai, Xiang-Ru; Wang, Li-Hua; Ren, Jia-Qiang; Bai, Xiang-Wei; Zeng, Ling-Wen; Shen, Ai-Guo; Hu, Ji-MingAnalytical Chemistry (Washington, DC, United States) (2019), 91 (4), 2955-2963CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Establishing an accurate, simple, and rapid serodiagnosis method aiming for specific cancer antigens is critically important for the clin. diagnosis, therapy, and prognostication of cancer. Currently, surface-enhanced Raman scattering (SERS) readout techniques challenge fluorescent-based detection methods in terms of both optical stability and more importantly multiple detection capability, which become more desirable for clin. diagnostics. The authors thus started using an interference-free mixing SERS emission (m-SERS) readout to simultaneously indicate, for the first time, three specific liver cancer antigens, including α-fetoprotein (AFP), carcinoembryonic antigen (CEA), and ferritin (FER), even in one clin. serum sample. Here, three triple bonds (C≡N and C≡C) coded SERS tags contribute sep. SERS emissions located at 2105, 2159, and 2227 cm-1, resp.; must have one-to-one correspondence from AFP, to FER, to CEA, In the process of detection, the mature double antibody sandwich gave microscale core-satellite assembly structure between a magnetic bead (MB) and single SERS tags, and therefore a pure and single SERS emission can be obsd. under the routine excitation laser spot. Because of the action of magnetic force, the uniform 3D packing of SERS tags absorbed MBs will in contrast generate a so-called m-SERS signals. With the help of enrichment and sepn. by MBs, the proposed m-SERS immunoassay provides an extremely rapid, sensitive, and accurate soln. for multiplex detection of antigens or other biomarkers. Herein, the limit of detection (LOD) for simultaneous m-SERS detection of AFP, CEA, and FER was 0.15, 20, and 4 pg/mL, resp. As expected for 39 clin. serum samples, simultaneous detection of ternary specific antigens can significantly improve the accuracy of liver cancer diagnosis.
- 242Gao, M.-Y.; Chen, Q.; Li, W.; Shen, A.-G.; Hu, J.-M. Combined Surface-Enhanced Raman Scattering Emissions for High-Throughput Optical Labels on Micrometer-Scale Objects. Anal. Chem. 2019, 91, 13866– 13873, DOI: 10.1021/acs.analchem.9b03357Google Scholar242Combined Surface-Enhanced Raman Scattering Emissions for High-Throughput Optical Labels on Micrometer-Scale ObjectsGao, Meng-Yue; Chen, Qiao; Li, Wei; Shen, Ai-Guo; Hu, Ji-MingAnalytical Chemistry (Washington, DC, United States) (2019), 91 (21), 13866-13873CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)High-throughput optical labeling technologies have become increasingly important with the growing demands for mol. detection, disease diagnosis, and drug discovery. In this thought, a series of CN-bridged coordination polymer encapsulated gold nanoparticles have been developed as a universal and interference-free optical label through a facile and auxiliary agent-free self-assembly route. Moreover, surface-enhanced Raman scattering (SERS) emissions of CN-bridge can be tuned flexibly by simple replacement of Fe2+/Fe3+ with other metal ions relying on synthesis of three Prussian blue analogs encapsulated gold nanoparticles (Au@PBA NPs). Thus, three distinct Raman frequencies have been acquired, merely replaced the metal irons. Based on the potential super-multiplex optical label, space-confined surface-enhanced Raman scattering (SERS) emissions has been realized. Relying on 'Abbe theorem', the focused laser allows the pure and single triple bond-coded SERS emissions being combined into a unique and independent output, so called 'combined SERS emission' (c-SERS), if the Au@PBA NPs were confined into one micron-scale object. This study demonstrated c-SERS may simultaneously provide 2n-1 optical labels only using n single emissions in Raman-silent region for micron-size objects.
- 243Zeng, Y.; Ren, J.; Shen, A.; Hu, J. Field and Pretreatment-Free Detection of Heavy-Metal Ions in Organic Polluted Water through an Alkyne-Coded SERS Test Kit. Acs Appl. Mater. Inter 2016, 8, 27772– 27778, DOI: 10.1021/acsami.6b09722Google ScholarThere is no corresponding record for this reference.
- 244Zeng, Y.; Ren, J.-Q.; Wang, S.-K.; Mai, J.-M.; Qu, B.; Zhang, Y.; Shen, A.-G.; Hu, J.-M. Rapid and Reliable Detection of Alkaline Phosphatase by a Hot Spots Amplification Strategy Based on Well-Controlled Assembly on Single Nanoparticle. Acs Appl. Mater. Inter 2017, 9, 29547– 29553, DOI: 10.1021/acsami.7b09336Google ScholarThere is no corresponding record for this reference.
- 245Zhang, Y.; Zou, Y.; Liu, F.; Xu, Y.; Wang, X.; Li, Y.; Liang, H.; Chen, L.; Chen, Z.; Tan, W. Stable Graphene-Isolated-Au-Nanocrystal for Accurate and Rapid Surface Enhancement Raman Scattering Analysis. Anal. Chem. 2016, 88, 10611– 10616, DOI: 10.1021/acs.analchem.6b02958Google Scholar245Stable Graphene-Isolated-Au-Nanocrystal for Accurate and Rapid Surface Enhancement Raman Scattering AnalysisZhang, Yin; Zou, Yuxiu; Liu, Fang; Xu, Yiting; Wang, Xuewei; Li, Yunjie; Liang, Hao; Chen, Long; Chen, Zhuo; Tan, WeihongAnalytical Chemistry (Washington, DC, United States) (2016), 88 (21), 10611-10616CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Various interferences from measurement conditions and substrate inhomogeneity are known confounding factors for poor reproducibility, which is a challenge in surface-enhanced Raman scattering (SERS) quantification. To address these issues, novel substrates and versatile internal stds. have been designed and the repeatability is improved to some degree. However, these internal stds. are either complex or unstable enough to resist harsh environments such as acid and oxidn. Graphene-isolated-Au-nanocrystal (GIAN) has unique properties and been applied for cell multimodal imaging and chemotherapy but not for SERS quantification anal. yet. Herein, the authors chose GIANs to improve the accuracy of SERS anal. GIAN integrates the SERS effect and internal std. into a simple nanoparticle and is an ideal platform for SERS anal. given its superior properties: (1) chem. stability, it remains stable in strong acid and oxidn., even mimic bioenvironment; (2) a simple core-shell structure, with a thin graphitic shell which is not only a protector that avoids inner Au catalysis unnecessary reaction but also an internal std. to eliminate the interference during the Raman detections; (3) the big-Π structure can absorb target mol. thus achieving an enrichment effect and quenching background fluorescence. Laser power, focus, and substrate fluctuations as well as coexist substance interferences were studied and the accuracy was improved greatly with the introduction of 2D band internal std. in Raman silent region with less background. Moreover, GIAN was applied for crystal violet detn. directly on fish muscle and scale, which was rapid and convenient without complex extn. process. All these results indicate GIAN is an optimum choice for SERS anal. in complex systems.
- 246Meng, X.; Wang, H.; Chen, N.; Ding, P.; Shi, H.; Zhai, X.; Su, Y.; He, Y. A Graphene–Silver Nanoparticle–Silicon Sandwich SERS Chip for Quantitative Detection of Molecules and Capture, Discrimination, and Inactivation of Bacteria. Anal. Chem. 2018, 90, 5646– 5653, DOI: 10.1021/acs.analchem.7b05139Google Scholar246A Graphene-Silver Nanoparticle-Silicon Sandwich SERS Chip for Quantitative Detection of Molecules and Capture, Discrimination, and Inactivation of BacteriaMeng, Xinyu; Wang, Houyu; Chen, Na; Ding, Pan; Shi, Huayi; Zhai, Xia; Su, Yuanyuan; He, YaoAnalytical Chemistry (Washington, DC, United States) (2018), 90 (9), 5646-5653CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)There currently exists increasing concerns on the development of a kind of high-performance SERS platform, which is suitable for sensing applications ranging from the mol. to cellular (e.g., bacteria) level. Herein, we develop a novel kind of universal SERS chip, made of graphene (G)-silver nanoparticle (AgNP)-silicon (Si) sandwich nanohybrids (G@AgNPs@Si), in which AgNPs are in situ grown on a silicon wafer through hydrofluoric acid-etching-assisted chem. redn., followed by coating with single-layer graphene via a polymer-protective etching method. The resultant chip features a strong, stable, reproducible surface-enhanced Raman scattering (SERS) effect and reliable quant. capability. By virtues of these merits, the G@AgNPs@Si platform is capable for not only mol. detection and quantification but also cellular anal. in real systems. As a proof-of-concept application, the chip allows ultrahigh sensitive and reliable detection of ATP, with a detection limit of ∼1 pM. In addn., the chip, serving as a novel multifunctional platform, enables simultaneous capture, discrimination, and inactivation of bacteria. Typically, the bacterial capture efficiency is 54% at 108 CFU mL-1 bacteria, and the antibacterial rate reaches 93% after 24 h of treatment. Of particular note, Escherichia coli and Staphylococcus aureus spiked into blood can be readily distinguished via the chip, suggesting its high potential for clin. applications.
- 247Yin, Y.; Li, Q.; Ma, S.; Liu, H.; Dong, B.; Yang, J.; Liu, D. Prussian Blue as a Highly Sensitive and Background-Free Resonant Raman Reporter. Anal. Chem. 2017, 89, 1551– 1557, DOI: 10.1021/acs.analchem.6b03521Google Scholar247Prussian Blue as a Highly Sensitive and Background-Free Resonant Raman ReporterYin, Yongmei; Li, Qiang; Ma, Sisi; Liu, Huiqiao; Dong, Bo; Yang, Jie; Liu, DingbinAnalytical Chemistry (Washington, DC, United States) (2017), 89 (3), 1551-1557CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)The authors report a surprising discovery that Prussian blue (PB) can be employed as a highly sensitive and background-free resonant Raman reporter. Conventional Raman reporters show multiple spectral bands in the fingerprint region, which are generally overlapped with those from dominant endogenous biomols., and are thus difficult to be sepd. Herein, PB only possesses a strong and sharp single-band in the cellular Raman-silent region, where no Raman signals from biol. species were obsd. Therefore, the Raman spectra from PB and endogenous biomols. are completely resolved without resorting to complicated spectral unmixing. Moreover, PB holds a strong UV-visible absorption band between 500 and 900 nm, which is resonant with the incident detection lasers, providing extremely high sensitivity. Through assembly of PB onto plasmonic cores, a new surface-enhanced resonance Raman scattering (SERRS) probe was achieved with a high signal-to-background ratio (SBR). The authors demonstrated the performance of the PB-based SERRS tags for high-sensitivity immunoassay and cancer cell imaging.
- 248Li, J.; Liu, F.; Ye, J. Boosting the Brightness of Thiolated Surface-Enhanced Raman Scattering Nanoprobes by Maximal Utilization of the Three-Dimensional Volume of Electromagnetic Fields. J. Phys. Chem. Lett. 2022, 13, 6496– 6502, DOI: 10.1021/acs.jpclett.2c01741Google ScholarThere is no corresponding record for this reference.
- 249Li, J.; Liu, F.; Bi, X.; Ye, J. Imaging immune checkpoint networks in cancer tissues with supermultiplexed SERS nanoprobes. Biomaterials 2023, 302, 122327, DOI: 10.1016/j.biomaterials.2023.122327Google ScholarThere is no corresponding record for this reference.
- 250Smith, A. M.; Mancini, M. C.; Nie, S. Second window for in vivo imaging. Nat. Nanotechnol. 2009, 4, 710– 711, DOI: 10.1038/nnano.2009.326Google Scholar250Second window for in vivo imagingSmith, Andrew M.; Mancini, Michael C.; Nie, ShumingNature Nanotechnology (2009), 4 (11), 710-711CODEN: NNAABX; ISSN:1748-3387. (Nature Publishing Group)Enhanced fluorescence from carbon nanotubes and advances in near-IR cameras have opened up a new wavelength window for small animal imaging.
- 251Kenry; Duan, Y.; Liu, B. Recent Advances of Optical Imaging in the Second Near-Infrared Window. Adv. Mater. 2018, 30, 1802394, DOI: 10.1002/adma.201802394Google ScholarThere is no corresponding record for this reference.
- 252Deng, B.; Zhang, Y.; Qiu, G.; Li, J.; Lin, L. L.; Ye, J. NIR-II Surface-Enhanced Raman Scattering Nanoprobes in Biomedicine: Current Impact and Future Directions. Small 2024, 2402235, DOI: 10.1002/smll.202402235Google ScholarThere is no corresponding record for this reference.
- 253Lane, L. A.; Xue, R.; Nie, S. Emergence of two near-infrared windows for in vivo and intraoperative SERS. Curr. Opin. Chem. Biol. 2018, 45, 95– 103, DOI: 10.1016/j.cbpa.2018.03.015Google Scholar253Emergence of two near-infrared windows for in vivo and intraoperative SERSLane, Lucas A.; Xue, Ruiyang; Nie, ShumingCurrent Opinion in Chemical Biology (2018), 45 (), 95-103CODEN: COCBF4; ISSN:1367-5931. (Elsevier B.V.)A review. Two clear windows in the near-IR (NIR) spectrum are of considerable current interest for in vivo mol. imaging and spectroscopic detection. The main rationale is that near-IR light can penetrate biol. tissues such as skin and blood more efficiently than visible light because these tissues scatter and absorb less light at longer wavelengths. The first clear window, defined as light wavelengths between 650 nm and 950 nm, has been shown to be far superior for in vivo and intraoperative optical imaging than visible light. The second clear window, operating in the wavelength range of 1000-1700 nm, has been reported to further improve detection sensitivity, spatial resoln., and tissue penetration because tissue photon scattering and background interference are further reduced at longer wavelengths. Here we discuss recent advances in developing biocompatible plasmonic nanoparticles for in vivo and intraoperative surface-enhanced Raman scattering (SERS) in both the first and second NIR windows. In particular, a new class of 'broad-band' plasmonic nanostructures is well suited for surface Raman enhancement across a broad range of wavelengths allowing a direct comparison of detection sensitivity and tissue penetration between the two NIR window. Also, optimized and encoded SERS nanoparticles are generally nontoxic and are much brighter than near-IR quantum dots (QDs), raising new possibilities for ultrasensitive detection of microscopic tumors and image-guided precision surgery.
- 254Antaris, A. L.; Chen, H.; Cheng, K.; Sun, Y.; Hong, G.; Qu, C.; Diao, S.; Deng, Z.; Hu, X.; Zhang, B.; Zhang, X.; Yaghi, O. K.; Alamparambil, Z. R.; Hong, X.; Cheng, Z.; Dai, H. A small-molecule dye for NIR-II imaging. Nat. Mater. 2016, 15, 235– 242, DOI: 10.1038/nmat4476Google Scholar254A small-molecule dye for NIR-II imagingAntaris, Alexander L.; Chen, Hao; Cheng, Kai; Sun, Yao; Hong, Guosong; Qu, Chunrong; Diao, Shuo; Deng, Zixin; Hu, Xianming; Zhang, Bo; Zhang, Xiaodong; Yaghi, Omar K.; Alamparambil, Zita R.; Hong, Xuechuan; Cheng, Zhen; Dai, HongjieNature Materials (2016), 15 (2), 235-242CODEN: NMAACR; ISSN:1476-1122. (Nature Publishing Group)Fluorescent imaging of biol. systems in the second near-IR window (NIR-II) can probe tissue at centimetre depths and achieve micrometre-scale resoln. at depths of millimetres. Unfortunately, all current NIR-II fluorophores are excreted slowly and are largely retained within the reticuloendothelial system, making clin. translation nearly impossible. Here, we report a rapidly excreted NIR-II fluorophore (∼90% excreted through the kidneys within 24 h) based on a synthetic 970-Da org. mol. (CH1055). The fluorophore outperformed indocyanine green (ICG)-a clin. approved NIR-I dye-in resolving mouse lymphatic vasculature and sentinel lymphatic mapping near a tumor. High levels of uptake of PEGylated-CH1055 dye were obsd. in brain tumors in mice, suggesting that the dye was detected at a depth of ∼4 mm. The CH1055 dye also allowed targeted mol. imaging of tumors in vivo when conjugated with anti-EGFR Affibody. Moreover, a superior tumor-to-background signal ratio allowed precise image-guided tumor-removal surgery.
- 255Shan, B.; Pu, Y.; Chen, Y.; Liao, M.; Li, M. Novel SERS labels: Rational design, functional integration and biomedical applications. Coord. Chem. Rev. 2018, 371, 11– 37, DOI: 10.1016/j.ccr.2018.05.007Google Scholar255Novel SERS labels: Rational design, functional integration and biomedical applicationsShan, Beibei; Pu, Yuhan; Chen, Yingfan; Liao, Mengling; Li, MingCoordination Chemistry Reviews (2018), 371 (), 11-37CODEN: CCHRAM; ISSN:0010-8545. (Elsevier B.V.)Driven by the growing demand for healthcare and point-of-care test applications, next-generation diagnostic tools of diseases require sensing platforms that enable rapid, quant. readout of analytes with excellent specificity and sensitivity. Although label-free detection permits simplicity, flexibility and high specificity, it has usually poor throughput, limited sensitivity and requires professional instrumentation. Label-based detection using optical labels overcomes many of these drawbacks and has been demonstrated to be an effective alternative for improved sensing performances. The current research focus has been directed towards innovating high-performance optical labels for ultrasensitive biosensing and disease diagnostics in place of conventional optical labels. Surface-enhanced Raman scattering (SERS) labels have proven to be excellent labels for biosensing because of their merits in many aspects, such as flexibility, less interference from biol. matrixes, high photostability, easy multiplex encoding, etc. These fantastic features make SERS labels particularly suitable for ultrasensitive detection of disease biomarkers in body fluids and targeted imaging of diseased cells and tissues, resp. In this Review, we introduce the design and deployment of SERS labels for ultrasensitive detection, and summarize recent research progress in the development of SERS label-based sensing platforms and their applications in disease biomarker detection, targeted cellular imaging and spectroscopic detection of tumor lesions. First, we will discuss the design principles and comprehensive considerations of SERS labels, and the on-demand integration of functionalities. Next, we introduce the design of SERS sensing platforms on basis of SERS labels for ultrasensitive and selective detection of diverse pathol.-related biomarkers, including proteins, nucleic acids, small mols. and inorg. ions. In addn., through the rational incorporation of targeting ligands on SERS labels, novel SERS probes are created for targeting near-IR (NIR) imaging and spectroscopic detection of tumor, taking advantages of large NIR light penetration depth, high brightness, stability, etc. Our and other research efforts have demonstrated the promising potential of SERS label-based sensing platforms for detection of diverse circulating biomarkers for non-invasive disease diagnostics and deep-tissue spectroscopic detection of tumor. It is believed that this review will motivate further exploration of clin. applications of SERS labels in near future.
- 256Reguera, J.; Langer, J.; Jiménez de Aberasturi, D.; Liz-Marzán, L. M. Anisotropic metal nanoparticles for surface enhanced Raman scattering. Chem. Soc. Rev. 2017, 46, 3866– 3885, DOI: 10.1039/C7CS00158DGoogle Scholar256Anisotropic metal nanoparticles for surface enhanced Raman scatteringReguera, Javier; Langer, Judith; Jimenez de Aberasturi, Dorleta; Liz-Marzan, Luis M.Chemical Society Reviews (2017), 46 (13), 3866-3885CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)The optimization of the enhancement of Raman scattering by plasmonic effects is largely detd. by the properties of the enhancing substrates. The main parameters behind this effect are related to the morphol. of plasmonic nanoparticles and their relative distribution within the substrate. We focus this tutorial review on the effects of nanoparticle morphol., for the particular case of anisotropic metal nanoparticles. Anisotropy in silver and gold nanoparticles offers the possibility to tailor their plasmonic properties and intrinsic electromagnetic "hotspots". We describe the effect of varying particle size and shape on the SERS signal, focusing on the most common anisotropic morphologies used for SERS. Especial emphasis is made on existing comparative studies that shed light on the effect of nanoparticle anisotropy on their enhancement capabilities. We aim at providing a general perspective toward understanding the general key factors and highlighting the difficulty in quant. detg. SERS performance.
- 257He, H.; Zhang, Y.; Zhu, S.; Ye, J.; Lin, L. Resonant Strategy in Designing NIR-II SERS Nanotags: A Quantitative Study. J. Phys. Chem. C 2022, 126, 12575– 12581, DOI: 10.1021/acs.jpcc.2c02512Google ScholarThere is no corresponding record for this reference.
- 258Chen, Y.-S.; Zhao, Y.; Yoon, S. J.; Gambhir, S. S.; Emelianov, S. Miniature gold nanorods for photoacoustic molecular imaging in the second near-infrared optical window. Nat. Nanotechnol. 2019, 14, 465– 472, DOI: 10.1038/s41565-019-0392-3Google Scholar258Miniature gold nanorods for photoacoustic molecular imaging in the second near-infrared optical windowChen, Yun-Sheng; Zhao, Yang; Yoon, Soon Joon; Gambhir, Sanjiv Sam; Emelianov, StanislavNature Nanotechnology (2019), 14 (5), 465-472CODEN: NNAABX; ISSN:1748-3387. (Nature Research)In photoacoustic imaging, the second near-IR (NIR-II) window is where tissue generates the least background signal. However, the large size of the few available contrast agents in this spectral range impedes their pharmacokinetics and decreases their thermal stability, leading to unreliable photoacoustic imaging. Here, the authors report the synthesis of miniaturized gold nanorods absorbing in the NIR-II that are 5-11 times smaller than regular-sized gold nanorods with a similar aspect ratio. Under nanosecond pulsed laser illumination, small nanorods are ∼3 times more thermally stable and generate 3.5 times stronger photoacoustic signal than their absorption-matched larger counterparts. These unexpected findings are confirmed using theor. and numerical anal., showing that photoacoustic signal is not only proportional to the optical absorption of the nanoparticle soln. but also to the surface-to-vol. ratio of the nanoparticles. In living tumor-bearing mice, these small targeted nanorods display a 30% improvement in efficiency of agent delivery to tumors and generate 4.5 times greater photoacoustic contrast.
- 259Tsai, M.-F.; Chang, S.-H. G.; Cheng, F.-Y.; Shanmugam, V.; Cheng, Y.-S.; Su, C.-H.; Yeh, C.-S. Au Nanorod Design as Light-Absorber in the First and Second Biological Near-Infrared Windows for in Vivo Photothermal Therapy. ACS Nano 2013, 7, 5330– 5342, DOI: 10.1021/nn401187cGoogle Scholar259Au Nanorod Design as Light-Absorber in the First and Second Biological Near-Infrared Windows for in Vivo Photothermal TherapyTsai, Ming-Fong; Chang, Shih-Hui Gilbert; Cheng, Fong-Yu; Shanmugam, Vijayakumar; Cheng, Yu-Sheng; Su, Chia-Hao; Yeh, Chen-ShengACS Nano (2013), 7 (6), 5330-5342CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Photothermal cancer therapy using near-IR (NIR) laser radiation is an emerging treatment. In the NIR region, two biol. transparency windows are located in 650-950 nm (first NIR window) and 1000-1350 nm (second NIR window) with optimal tissue transmission obtained from low scattering and energy absorption, thus providing max. radiation penetration through tissue and minimizing autofluorescence. To date, intensive effort has resulted in the generation of various methods that can be used to shift the absorbance of nanomaterials to the 650-950 nm NIR regions for studying photoinduced therapy. However, NIR light absorbers smaller than 100 nm in the second NIR region have been scant. We report that a Au nanorod (NR) can be designed with a rod-in-shell (rattle-like) structure smaller than 100 nm that is tailored to be responsive to the first and second NIR windows, in which we can perform hyperthermia-based therapy. In vitro performance clearly displays high efficacy in the NIR photothermal destruction of cancer cells, showing large cell-damaged area beyond the laser-irradiated area. This marked phenomenon has made the rod-in-shell structure a promising hyperthermia agent for the in vivo photothermal ablation of solid tumors when activated using a continuous-wave 808 m (first NIR window) or a 1064 nm (second NIR window) diode laser. We tailored the UV-vis-NIR spectrum of the rod-in-shell structure by changing the gap distance between the Au NR core and the AuAg nanoshell, to evaluate the therapeutic effect of using a 1064 nm diode laser. Regarding the first NIR window with the use of an 808 nm diode laser, rod-in-shell particles exhibit a more effective anticancer efficacy in the laser ablation of solid tumors compared to Au NRs.
- 260Skrabalak, S. E.; Au, L.; Li, X.; Xia, Y. Facile synthesis of Ag nanocubes and Au nanocages. Nat. Protoc 2007, 2, 2182– 2190, DOI: 10.1038/nprot.2007.326Google Scholar260Facile synthesis of Ag nanocubes and Au nanocagesSkrabalak, Sara E.; Au, Leslie; Li, Xingde; Xia, YounanNature Protocols (2007), 2 (9), 2182-2190CODEN: NPARDW; ISSN:1750-2799. (Nature Publishing Group)This protocol describes a method for the synthesis of Ag nanocubes and their subsequent conversion into Au nanocages via the galvanic replacement reaction. The Ag nanocubes were prepd. by a rapid (reaction time < 15 min), sulfide-mediated polyol method in which Ag(I) is reduced to Ag(0) by ethylene glycol in the presence of poly(vinyl pyrrolidone) (PVP) and a trace amt. of Na2S. When the concn. of Ag atoms reaches supersatn., they agglomerate to form seeds that then grow into Ag nanostructures. The presence of both PVP and Na2S facilitate the formation of nanocubes. With this method, Ag nanocubes can be prepd. and isolated for use within ∼3 h. The Ag nanocubes can then serve as sacrificial templates for the prepn. of Au nanocages, with a method for their prepn. also described herein. The procedure for Au nanocage prepn. and isolation requires ∼5 h.
- 261Shan, B.; Li, L.; Zhao, Y.; Wang, H.; Li, M. Near-Infrared II Plasmonic Au@Au–Ag Dot-in-Cubic Nanoframes for In Vivo Surface-Enhanced Raman Spectroscopic Detection and Photoacoustic Imaging. Adv. Funct. Mater. 2021, 31, 2103186, DOI: 10.1002/adfm.202103186Google Scholar261Near-Infrared II Plasmonic Au@Au-Ag Dot-in-Cubic Nanoframes for In Vivo Surface-Enhanced Raman Spectroscopic Detection and Photoacoustic ImagingShan, Beibei; Li, Linhu; Zhao, Yawen; Wang, Haitao; Li, MingAdvanced Functional Materials (2021), 31 (29), 2103186CODEN: AFMDC6; ISSN:1616-301X. (Wiley-VCH Verlag GmbH & Co. KGaA)Near-IR II (NIR-II) plasmonic noble-metallic nanostructures are highly desirable for in vivo photodiagnostics because of their multiple functionalities and deep-tissue optical imaging capability. Herein, a novel class of Au@Au-Ag dot-in-cubic nanoframes (DCFs) comprising a solid Au core and a Au-Ag alloy shell with a wall hole on each side face is reported, which exhibit remarkable plasmonic properties spectrally tunable beyond 1400 nm while maintaining a small size. The synthesis of Au@Au-Ag DCFs is principally based on the facet-selective etching of Ag atoms and co-deposition of Au and Ag atoms on the edges and corners of Au@Ag dot-in-cubes. The geometry (e.g., edge length and wall hole size) can be controllably tailored by simply varying the silver nitrate and chloroauric acid concns. Superior in vitro and in vivo NIR-II photoacoustic imaging performances of Au@Au-Ag DCFs are demonstrated. Addnl., remarkable NIR-II surface-enhanced Raman spectroscopy (SERS) activity of Au@Au-Ag DCFs is evidenced with the max. NIR-II SERS enhancement occurring at a plasmon resonance wavelength blue-shifting from the incident laser wavelength and an excellent effective detection depth. Finally, the potential of the developed Au@Au-Ag DCFs is highlighted for in vivo NIR-II SERS detection of microtumors in animals.
- 262Li, L.; Jiang, R.; Shan, B.; Lu, Y.; Zheng, C.; Li, M. Near-infrared II plasmonic porous cubic nanoshells for in vivo noninvasive SERS visualization of sub-millimeter microtumors. Nat. Commun. 2022, 13, 5249, DOI: 10.1038/s41467-022-32975-wGoogle Scholar262Near-infrared II plasmonic porous cubic nanoshells for in vivo noninvasive SERS visualization of sub-millimeter microtumorsLi, Linhu; Jiang, Renting; Shan, Beibei; Lu, Yaxuan; Zheng, Chao; Li, MingNature Communications (2022), 13 (1), 5249CODEN: NCAOBW; ISSN:2041-1723. (Nature Portfolio)In vivo surface-enhanced Raman scattering (SERS) imaging allows non-invasive visualization of tumors for intraoperative guidance and clin. diagnostics. However, the in vivo utility of SERS is greatly hampered by the strong optical scattering and autofluorescence background of biol. tissues and the lack of highly active plasmonic nanostructures. Herein, we report a class of porous nanostructures comprising a cubic AuAg alloy nanoshell and numerous nanopores. Such porous nanostructures exhibit excellent near-IR II plasmonic properties tunable in a broad spectral range by varying the pore features while maintaining a small dimension. We demonstrate their exceptional near-IR II SERS performance varying with the porous properties. Addnl., near-IR II SERS probes created with porous cubic AuAg nanoshells are demonstrated with remarkable capability for in vivo visualization of sub-millimeter microtumors in a living mouse model. Our near-IR II SERS probes hold great potentials for precise demarcation of tumor margins and identification of microscopic tumors.
- 263Deng, B.; Wang, Y.; Bu, X.; Li, J.; Lu, J.; Lin, L. L.; Wang, Y.; Chen, Y.; Ye, J. Sentinel lymph node identification using NIR-II ultrabright Raman nanotags on preclinical models. Biomaterials 2024, 308, 122538, DOI: 10.1016/j.biomaterials.2024.122538Google ScholarThere is no corresponding record for this reference.
- 264Lu, Y.; Li, M. Rational Design of Near-infrared II Plasmonic Optofunctional Materials for Diagnostic and Therapeutic Applications. Adv. Funct. Mater. 2024, 34, 2312753, DOI: 10.1002/adfm.202312753Google ScholarThere is no corresponding record for this reference.
- 265Li, J.; Deng, B.; Ye, J. Fluorescence-free bis(dithiolene)nickel dyes for surface-enhanced resonance Raman imaging in the second near-infrared window. Biomaterials 2023, 300, 122211, DOI: 10.1016/j.biomaterials.2023.122211Google ScholarThere is no corresponding record for this reference.
- 266Tian, Y.-F.; Zhou, W.; Yin, B.-C.; Ye, B.-C. Highly sensitive surface-enhanced Raman scattering detection of adenosine triphosphate based on core–satellite assemblies. Analytical Methods 2017, 9, 6038– 6043, DOI: 10.1039/C7AY02096AGoogle ScholarThere is no corresponding record for this reference.
- 267Wang, Y.; Salehi, M.; Schütz, M.; Rudi, K.; Schlücker, S. Microspectroscopic SERS detection of interleukin-6 with rationally designed gold/silver nanoshells. Analyst 2013, 138, 1764– 1771, DOI: 10.1039/c3an36610cGoogle Scholar267Microspectroscopic SERS detection of interleukin-6 with rationally designed gold/silver nanoshellsWang, Yuling; Salehi, Mohammad; Schuetz, Max; Rudi, Katharina; Schluecker, SebastianAnalyst (Cambridge, United Kingdom) (2013), 138 (6), 1764-1771CODEN: ANALAO; ISSN:0003-2654. (Royal Society of Chemistry)Rationally designed gold/silver nanoshells (Au/Ag-NS) with plasmon resonances optimized for red laser excitation in order to minimize autofluorescence from clin. samples exhibit scattering cross-sections, which are ca. one order of magnitude larger compared with solid quasi-spherical gold nanoparticles (Au-NPs) of the same size. Hydrophilic stabilization and sterical accessibility for subsequent bioconjugation of Au/Ag-NS is achieved by coating their surface with a self-assembled monolayer (SAM) of rationally designed Raman reporter mols. comprising terminal mono- and tri-ethylene glycol (EG) spacers, resp. The stability of the hydrophilically stabilized metal colloid was tested under different conditions. In contrast to metal colloids coated with a SAM without terminal EG spacers, the hydrophilically stabilized SERS particles do not aggregate under physiol. relevant conditions, i.e., buffer solns. with high ionic strength. Using these rationally designed SERS particles in conjunction with a microspectroscopic acquisition scheme, a sandwich immunoassay for the sensitive detection of interleukin-6 (IL-6) was developed. Several control expts. demonstrate the high specificity of the assay towards IL-6, with a lowest detectable concn. of ca. 1 pg mL-1. The signal strength of the Au/Ag-NS is at least one order of magnitude higher compared with hydrophilically stabilized, non-aggregated solid quasi-spherical Au-NPs of the same size.
- 268Wang, H.; Wang, Y.; Yuan, C.; Xu, X.; Zhou, W.; Huang, Y.; Lu, H.; Zheng, Y.; Luo, G.; Shang, J.; Sui, M. Polyethylene glycol (PEG)-associated immune responses triggered by clinically relevant lipid nanoparticles in rats. NPJ. Vaccines 2023, 8, 169, DOI: 10.1038/s41541-023-00766-zGoogle ScholarThere is no corresponding record for this reference.
- 269Bodelón, G.; Montes-García, V.; Fernández-López, C.; Pastoriza-Santos, I.; Pérez-Juste, J.; Liz-Marzán, L. M. Au@pNIPAM SERRS Tags for Multiplex Immunophenotyping Cellular Receptors and Imaging Tumor Cells. Small 2015, 11, 4149– 4157, DOI: 10.1002/smll.201500269Google Scholar269Au@pNIPAM SERRS Tags for Multiplex Immunophenotyping Cellular Receptors and Imaging Tumor CellsBodelon, Gustavo; Montes-Garcia, Veronica; Fernandez-Lopez, Cristina; Pastoriza-Santos, Isabel; Perez-Juste, Jorge; Liz-Marzan, Luis M.Small (2015), 11 (33), 4149-4157CODEN: SMALBC; ISSN:1613-6810. (Wiley-VCH Verlag GmbH & Co. KGaA)Detection technologies employing optically encoded particles have gained much interest toward clin. diagnostics and drug discovery, but the portfolio of available systems is still limited. The fabrication and characterization of highly stable surface-enhanced resonance Raman scattering (SERRS)-encoded colloids for the identification and imaging of proteins expressed in cells are reported. These plasmonic nanostructures are made of gold octahedra coated with poly(N-isopropylacrylamide) microgels and can be readily encoded with Raman active dyes while retaining high colloidal stability in biofluids. A layer-by-layer polyelectrolyte coating was used to seal the outer surface of the encoded particles and to provide a reactive surface for covalent conjugation with antibodies. The targeted multiplexing capabilities of the SERRS tags are demonstrated by the simultaneous detection and imaging of three tumor-assocd. surface biomarkers: epidermal growth factor receptor (EGFR), epithelial cell adhesion mol. (EpCAM), and homing cell adhesion mol. (CD44) by SERRS spectroscopy. The plasmonic microgels are able to discriminate tumor A431 (EGFR+/EpCAM+/CD44+) and nontumor 3T3 2.2 (EGFR-/EpCAM-/CD44+) cells while cocultured in vitro.
- 270Casado-Rodriguez, M. A.; Sanchez-Molina, M.; Lucena-Serrano, A.; Lucena-Serrano, C.; Rodriguez-Gonzalez, B.; Algarra, M.; Diaz, A.; Valpuesta, M.; Lopez-Romero, J. M.; Perez-Juste, J.; Contreras-Caceres, R. Synthesis of vinyl-terminated Au nanoprisms and nanooctahedra mediated by 3-butenoic acid: direct Au@pNIPAM fabrication with improved SERS capabilities. Nanoscale 2016, 8, 4557– 4564, DOI: 10.1039/C5NR08054AGoogle Scholar270Synthesis of vinyl-terminated Au nanoprisms and nanooctahedra mediated by 3-butenoic acid: direct Au@pNIPAM fabrication with improved SERS capabilitiesCasado-Rodriguez, M. A.; Sanchez-Molina, M.; Lucena-Serrano, A.; Lucena-Serrano, C.; Rodriguez-Gonzalez, B.; Algarra, M.; Diaz, A.; Valpuesta, M.; Lopez-Romero, J. M.; Perez-Juste, J.; Contreras-Caceres, R.Nanoscale (2016), 8 (8), 4557-4564CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)Here we describe the first seedless synthesis of vinyl-terminated Au nanotriangular prisms (AuNTPs) and nanooctahedra (AuNOC) in aq. media. This synthesis is performed by chem. redn. of chloroauric acid (HAuCl4) with 3-butenoic acid (3BA) in the presence of benzyldimethylammonium chloride (BDAC). The principal novelties of the presented method are the use of a mixt. of 3BA and BDAC, the synthesis of gold prisms and octahedra with controllable size, and the presence of terminal double bonds on the metal surface. Initially this method produces a mixt. of triangular gold nanoprisms and octahedra; however, both morphologies are successfully sepd. by surfactant micelle induced depletion interaction, reaching percentages up to~ 90%. Moreover, the alkene moieties present on the gold surface are exploited for the fabrication of hybrid core@shell particles. Gold octahedra and triangular prisms are easily encapsulated by free radical polymn. of N-isopropylacrylamide (NIPAM). Finally, in order to obtain a gold core with the most no. of tips, AuNTP@pNIPAM microgels were subjected to gold core overgrowth, thus resulting in star-shaped nanoparticles (AuSTs@pNIPAM). We use 4-amino-benzenethiol as the model analyte for SERS investigations. As expected, gold cores with tips and high curvature sites produced the highest plasmonic responses.
- 271Yokota, K.; Usuda, S.; Nishimura, N.; Takahashi, R.; Taoka, Y.; Kobayashi, S.; Tanaka, M.; Matsumura, K.; Yusa, S.-I. Self-Assembly and Drug Encapsulation Properties of Biocompatible Amphiphilic Diblock Copolymers. Langmuir 2025, 41 (1), 765– 773, DOI: 10.1021/acs.langmuir.4c04048Google ScholarThere is no corresponding record for this reference.
- 272Alipour, E.; Halverson, D.; McWhirter, S.; Walker, G. C. Phospholipid Bilayers: Stability and Encapsulation of Nanoparticles. Annu. Rev. Phys. Chem. 2017, 68, 261– 283, DOI: 10.1146/annurev-physchem-040215-112634Google Scholar272Phospholipid Bilayers: Stability and Encapsulation of NanoparticlesAlipour, Elnaz; Halverson, Duncan; McWhirter, Samantha; Walker, Gilbert C.Annual Review of Physical Chemistry (2017), 68 (), 261-283CODEN: ARPLAP; ISSN:0066-426X. (Annual Reviews)Nanoparticles are widely studied for their potential medical uses in diagnostics and therapeutics. The interface between a nanoparticle and its target has been a focus of research, both to guide the nanoparticle and to prevent it from deactivating. Given nature's frequent use of phospholipid vesicles as carriers, much attention has been paid to phospholipids as a vehicle for drug delivery. The phys. chem. of bilayer formation and nanoparticle encapsulation is complex, touching on fundamental properties of hydrophobicity. Understanding the design rules for particle synthesis and encapsulation is an active area of research. The aim of this review is to provide a perspective on what preparative guideposts have been empirically discovered and how these are related to theor. understanding. In addn., we aim to summarize how modern theory is beginning to help guide the design of functional particles that can effectively cross biol. membranes.
- 273Bruzas, I.; Brinson, B. E.; Gorunmez, Z.; Lum, W.; Ringe, E.; Sagle, L. Surface-Enhanced Raman Spectroscopy of Fluid-Supported Lipid Bilayers. ACS Appl. Mater. & Interfaces 2019, 11, 33442– 33451, DOI: 10.1021/acsami.9b09988Google ScholarThere is no corresponding record for this reference.
- 274Tam, N. C.; McVeigh, P. Z.; MacDonald, T. D.; Farhadi, A.; Wilson, B. C.; Zheng, G. Porphyrin-lipid stabilized gold nanoparticles for surface enhanced Raman scattering based imaging. Bioconjugate Chem. 2012, 23, 1726– 30, DOI: 10.1021/bc300214zGoogle Scholar274Porphyrin-Lipid Stabilized Gold Nanoparticles for Surface Enhanced Raman Scattering Based ImagingTam, Natalie C. M.; McVeigh, Patrick Z.; MacDonald, Thomas D.; Farhadi, Arash; Wilson, Brian C.; Zheng, GangBioconjugate Chemistry (2012), 23 (9), 1726-1730CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)A porphyrin-phospholipid conjugate with quenched fluorescence was utilized to serve as both the Raman dye and a stabilizing, biocompatible surface coating agent on gold nanoparticles. Through simple synthesis and validation with spectroscopy and confocal microscopy, it was shown that this porphyrin-phospholipid stabilized AuNP is a novel SERS probe capable of cellular imaging. To date, this is the first use of porphyrin as a Raman reporter mol. for SERS based imaging.
- 275Zheng, X.-S.; Hu, P.; Cui, Y.; Zong, C.; Feng, J.-M.; Wang, X.; Ren, B. BSA-Coated Nanoparticles for Improved SERS-Based Intracellular pH Sensing. Anal. Chem. 2014, 86, 12250– 12257, DOI: 10.1021/ac503404uGoogle Scholar275BSA-Coated Nanoparticles for Improved SERS-Based Intracellular pH SensingZheng, Xiao-Shan; Hu, Pei; Cui, Yan; Zong, Cheng; Feng, Jia-Min; Wang, Xin; Ren, BinAnalytical Chemistry (Washington, DC, United States) (2014), 86 (24), 12250-12257CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Local microenvironment pH sensing is one of the key parameters for the understanding of many biol. processes. As a noninvasive and high sensitive technique, surface-enhanced Raman spectroscopy (SERS) has attracted considerable interest in the detection of the local pH of live cells. We herein develop a facile way to prep. Au-(4-MPy)-BSA (AMB) pH nanosensor. The 4-MPy (4-mercaptopyridine) was used as the pH sensing mol. The modification of the nanoparticles with BSA not only provides a high sensitive response to pH changes ranging from pH 4.0 to 9.0 but also exhibits a high sensitivity and good biocompatibility, stability, and reliability in various solns. (including the solns. of high ionic strength or with complex compn. such as the cell culture medium), both in the aggregation state or after long-term storage. The AMB pH nanosensor shows great advantages for reliable intracellular pH anal. and has been successfully used to monitor the pH distribution of live cells and can address the grand challenges in SERS-based pH sensing for practical biol. applications.
- 276Blanco-Covián, L.; Montes-García, V.; Girard, A.; Fernández-Abedul, M. T.; Pérez-Juste, J.; Pastoriza-Santos, I.; Faulds, K.; Graham, D.; Blanco-López, M. C. Au@Ag SERRS tags coupled to a lateral flow immunoassay for the sensitive detection of pneumolysin. Nanoscale 2017, 9, 2051– 2058, DOI: 10.1039/C6NR08432JGoogle Scholar276Au@Ag SERRS tags coupled to a lateral flow immunoassay for the sensitive detection of pneumolysinBlanco-Covian, Lucia; Montes-Garcia, Veronica; Girard, Alexandre; Fernandez-Abedul, M. Teresa; Perez-Juste, Jorge; Pastoriza-Santos, Isabel; Faulds, Karen; Graham, Duncan; Blanco-Lopez, M. CarmenNanoscale (2017), 9 (5), 2051-2058CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)Establishing a definitive diagnosis of pneumonia using conventional tests is difficult and expensive. Lateral flow immunoassays (LFIAs) are an advantageous point of care (POC) test option, but they have some limitations in terms of detection and quantification. In this work we have developed a lateral flow immunoassay for the ultrasensitive detection of penumolysin employing plasmonic Surface-Enhanced Resonance Raman Scattering (SERRS) tag as labeled probe. The combination of Au@Ag core-shell nanoparticles as plasmonic platform and Rhodamine B Isothiocyanate as Raman reporter has allowed us to fabricate a SERRS tag with high efficiency and reliability. The limit of detection of the SERRS-based LFIA was 1 pg mL-1. This could be a strong foundation for a pneumonia diagnosis test based on pneumolysin detection.
- 277Sun, L.; Sung, K.-B.; Dentinger, C.; Lutz, B.; Nguyen, L.; Zhang, J.; Qin, H.; Yamakawa, M.; Cao, M.; Lu, Y.; Chmura, A. J.; Zhu, J.; Su, X.; Berlin, A. A.; Chan, S.; Knudsen, B. Composite Organic–Inorganic Nanoparticles as Raman Labels for Tissue Analysis. Nano Lett. 2007, 7, 351– 356, DOI: 10.1021/nl062453tGoogle Scholar277Composite Organic-Inorganic Nanoparticles as Raman Labels for Tissue AnalysisSun, Lei; Sung, Kung-Bin; Dentinger, Claire; Lutz, Barry; Nguyen, Lienchi; Zhang, Jingwu; Qin, Haoyu; Yamakawa, Mineo; Cao, Manqiu; Lu, Yu; Chmura, Aj; Zhu, Jing; Su, Xing; Berlin, Andrew A.; Chan, Selena; Knudsen, BeatriceNano Letters (2007), 7 (2), 351-356CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)Composite org.-inorg. nanoparticles (COINs) are novel optical labels for detection of biomols. The authors have previously developed methods to encapsulate COINs and to functionalize them with antibodies. Here the authors report the first steps toward application of COINs to the detection of proteins in human tissues. Two analytes, PSA and CK18, are detected simultaneously using two different COINs in a direct binding assay, and two different COINs are shown to simultaneously label PSA in tissue samples.
- 278Küstner, B.; Gellner, M.; Schütz, M.; Schöppler, F.; Marx, A.; Ströbel, P.; Adam, P.; Schmuck, C.; Schlücker, S. SERS labels for red laser excitation: silica-encapsulated SAMs on tunable gold/silver nanoshells. Angew. Chem., Int. Ed 2009, 48, 1950– 1953, DOI: 10.1002/anie.200804518Google ScholarThere is no corresponding record for this reference.
- 279Wang, C.; Yan, Q.; Liu, H.-B.; Zhou, X.-H.; Xiao, S.-J. Different EDC/NHS Activation Mechanisms between PAA and PMAA Brushes and the Following Amidation Reactions. Langmuir 2011, 27, 12058– 12068, DOI: 10.1021/la202267pGoogle Scholar279Different EDC/NHS Activation Mechanisms between PAA and PMAA Brushes and the Following Amidation ReactionsWang, Cuie; Yan, Qin; Liu, Hong-Bo; Zhou, Xiao-Hui; Xiao, Shou-JunLangmuir (2011), 27 (19), 12058-12068CODEN: LANGD5; ISSN:0743-7463. (American Chemical Society)IR spectroscopy was applied to investigate the well-known EDC/NHS (N-ethyl-N'-(3-(dimethylamino)propyl)carbodiimide/N-hydroxysuccinimide) activation details of poly(acrylic acid) (PAA) and poly(methacrylic acid) (PMAA) brushes grafted on porous silicon. Succinimidyl ester (NHS-ester) is generally believed to be the dominant intermediate product, conveniently used to immobilize biomols. contg. free primary amino groups via amide linkage. To the authors' surprise, the IR spectral details revealed that the EDC/NHS activation of PMAA generated anhydride (estd. at around 76% yield and 70% compn.), but not NHS-ester (around 5% yield and 11% compn.) under the well-documented reaction conditions, as the predominant intermediate product. In contrast, EDC/NHS activation of PAA still follows the general rule, i.e., the expected NHS-ester is the dominant intermediate product (around 45% yield and 57% compn.), anhydride the side product (40% yield and 28% compn.), under the optimum reaction conditions. The following amidation on PAA-based NHS-esters with a model amine-contg. compd., L-leucine Me ester, generated approx. 70% amides and 30% carboxylates. In contrast, amidation of PAA- or PMAA-based anhydrides with L-leucine Me ester only produced less than 30% amides but more than 70% carboxylates. The above reaction yields and percentage compns. were estd. by fitting the carbonyl stretching region with 5 possible species, NHS-ester, anhydride, N-acylurea, unreacted acid, unhydrolyzed tert-Bu ester, and using the Beer-Lambert law. The different surface chem. mechanisms will bring significant effects on the performance of surface chem.-derived devices such as biochips, biosensors, and biomaterials.
- 280Srivastava, I.; Xue, R.; Jones, J.; Rhee, H.; Flatt, K.; Gruev, V.; Nie, S. Biomimetic Surface-Enhanced Raman Scattering Nanoparticles with Improved Dispersibility, Signal Brightness, and Tumor Targeting Functions. ACS Nano 2022, 16, 8051– 8063, DOI: 10.1021/acsnano.2c01062Google Scholar280Biomimetic Surface-Enhanced Raman Scattering Nanoparticles with Improved Dispersibility, Signal Brightness, and Tumor Targeting FunctionsSrivastava, Indrajit; Xue, Ruiyang; Jones, Jamie; Rhee, Hyunjoon; Flatt, Kristen; Gruev, Viktor; Nie, ShumingACS Nano (2022), 16 (5), 8051-8063CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)The development of biocompatible and nontoxic surface-enhanced Raman scattering (SERS) nanoparticles is of considerable current interest because of their attractive biomedical applications such as ultrasensitive in vitro diagnostics, in vivo tumor imaging, and spectroscopy-guided cancer surgery. However, current SERS nanoparticles are prepd. and stored in aq. soln., have limited stability and dispersibility, and are not suitable for lyophilization and storage by freeze-drying or other means. Here, we report a simple but robust method to coat colloidal SERS nanoparticles by naturally derived biomimetic red blood cell membranes (RBCM), leading to a dramatic improvement in stability and dispersibility under freeze-thawing, lyophilization, heating, and physiol. conditions. The results demonstrate that the lyophilized SERS nanoparticles in the solid form can be readily dissolved and dispersed in physiol. buffer solns. A surprising finding is that the RBCM-coated SERS particles are considerably brighter (by as much as 5-fold) than PEGylated SERS particles under similar exptl. conditions. This addnl. enhancement is believed to arise from the hydrophobic nature of RBCM's hydrocarbon chains, which is known to reduce electronic dampening and boost electromagnetic field enhancement. A further advantage in using biomimetic membrane coatings is that the bilayer membrane structure allows nonvalent insertion of mol. ligands for tumor targeting. In particular, we show that cyclic-RGD, a tumor-targeting peptide, can be efficiently inserted into the membrane coatings of SERS nanoparticles for targeting the ανβ3 integrin receptors expressed on cancer cells. Thus, biomimetic RBCMs provide major advantages over traditional polyethylene glycols for prepg. SERS nanoparticles with improved dispersibility, higher signal intensity, and more efficient biofunctionalization.
- 281Srivastava, I.; Xue, R.; Huang, H.-K.; Wang, Z.; Jones, J.; Vasquez, I.; Pandit, S.; Lin, L.; Zhao, S.; Flatt, K.; Gruev, V.; Chen, Y.-S.; Nie, S. Biomimetic-Membrane-Protected Plasmonic Nanostructures as Dual-Modality Contrast Agents for Correlated Surface-Enhanced Raman Scattering and Photoacoustic Detection of Hidden Tumor Lesions. ACS Appl. Mater. & Interfaces 2024, 16, 8554– 8569, DOI: 10.1021/acsami.3c18488Google ScholarThere is no corresponding record for this reference.
- 282Srivastava, I.; Lew, B.; Wang, Y.; Blair, S.; George, M. B.; Hajek, B. S.; Bangru, S.; Pandit, S.; Wang, Z.; Ludwig, J.; Flatt, K.; Gruebele, M.; Nie, S.; Gruev, V. Cell-Membrane Coated Nanoparticles for Tumor Delineation and Qualitative Estimation of Cancer Biomarkers at Single Wavelength Excitation in Murine and Phantom Models. ACS Nano 2023, 17, 8465– 8482, DOI: 10.1021/acsnano.3c00578Google ScholarThere is no corresponding record for this reference.
- 283Gill, N.; Srivastava, I.; Tropp, J. Rational Design of NIR-II Emitting Conjugated Polymer Derived Nanoparticles for Image-Guided Cancer Interventions. Adv. Healthc Mater. 2024, 13, e2401297, DOI: 10.1002/adhm.202401297Google ScholarThere is no corresponding record for this reference.
- 284Stetciura, I. Y.; Yashchenok, A.; Masic, A.; Lyubin, E. V.; Inozemtseva, O. A.; Drozdova, M. G.; Markvichova, E. A.; Khlebtsov, B. N.; Fedyanin, A. A.; Sukhorukov, G. B.; Gorin, D. A.; Volodkin, D. Composite SERS-based satellites navigated by optical tweezers for single cell analysis. Analyst 2015, 140, 4981– 4986, DOI: 10.1039/C5AN00392JGoogle ScholarThere is no corresponding record for this reference.
- 285Messina, E.; Cavallaro, E.; Cacciola, A.; Saija, R.; Borghese, F.; Denti, P.; Fazio, B.; D’Andrea, C.; Gucciardi, P. G.; Iatì, M. A.; Meneghetti, M.; Compagnini, G.; Amendola, V.; Maragò, O. M. Manipulation and Raman Spectroscopy with Optically Trapped Metal Nanoparticles Obtained by Pulsed Laser Ablation in Liquids. J. Phys. Chem. C 2011, 115, 5115– 5122, DOI: 10.1021/jp109405jGoogle Scholar285Manipulation and Raman Spectroscopy with Optically Trapped Metal Nanoparticles Obtained by Pulsed Laser Ablation in LiquidsMessina, E.; Cavallaro, E.; Cacciola, A.; Saija, R.; Borghese, F.; Denti, P.; Fazio, B.; D'Andrea, C.; Gucciardi, P. G.; Iati, M. A.; Meneghetti, M.; Compagnini, G.; Amendola, V.; Marago, O. M.Journal of Physical Chemistry C (2011), 115 (12), 5115-5122CODEN: JPCCCK; ISSN:1932-7447. (American Chemical Society)Optical trapping of metal nanoparticles and aggregates were studied exptl. and theor. Light forces can be used to trap individual Au nanoaggregates of controlled size and structure obtained by laser ablation synthesis in soln. Due to their surface charge, no agglomeration of isolated nanoparticles was obsd. during trapping expts. and reliable optical force measurements of isolated and aggregated nanoparticles was possible through an anal. of the Brownian motion in the trap. The field-enhancement properties of these nanostructures enables surface-enhanced Raman spectroscopy of mols. adsorbed on aggregates optically trapped in a Raman tweezers setup. The authors finally discuss calcns. of extinction and optical forces based on a full electromagnetic scattering theory for aggregated Au nanostructures where the occurrence of plasmon resonances at longer wavelength play a crucial role in the enhancement of the trapping forces.
- 286Hong, S.; Shim, O.; Kwon, H.; Choi, Y. Autoenhanced Raman Spectroscopy via Plasmonic Trapping for Molecular Sensing. Anal. Chem. 2016, 88, 7633– 7638, DOI: 10.1021/acs.analchem.6b01451Google Scholar286Autoenhanced Raman Spectroscopy via Plasmonic Trapping for Molecular SensingHong, Soonwoo; Shim, On; Kwon, Hyosung; Choi, YeonhoAnalytical Chemistry (Washington, DC, United States) (2016), 88 (15), 7633-7638CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)As a label-free and sensitive biosensor, surface-enhanced Raman spectroscopy (SERS) is a rapidly emerging technique. However, because SERS spectra are obtained in the area of light excitation and the enhancement effect can be varied depending on the position of a substrate, it is important to match the enhanced area with an illuminated spot. Here, in order to overcome such difficulty, we demonstrated a new technique combining SERS with plasmonic trapping. By plasmonic trapping, we can collect gold nanoparticles (GNPs) in the middle of initially fabricated nanobowtie structures where a laser is excited. As a result of trapping GNPs, hot-spots are formed at that area. Because SERS is measured in the area irradiated by a laser, hot-spot can be simultaneously coincided with a detection site for SERS. By using this, we detected Rhodamine 6G to 100 pM. To further verify and improve the reproducibility of our technique, we also calcd. the elec. field distribution, trapping force and trapping potential.
- 287Dai, X.; Fu, W.; Chi, H.; Mesias, V. S. D.; Zhu, H.; Leung, C. W.; Liu, W.; Huang, J. Optical tweezers-controlled hotspot for sensitive and reproducible surface-enhanced Raman spectroscopy characterization of native protein structures. Nat. Commun. 2021, 12, 1292, DOI: 10.1038/s41467-021-21543-3Google Scholar287Optical tweezers-controlled hotspot for sensitive and reproducible surface-enhanced Raman spectroscopy characterization of native protein structuresDai, Xin; Fu, Wenhao; Chi, Huanyu; Mesias, Vince St. Dollente; Zhu, Hongni; Leung, Cheuk Wai; Liu, Wei; Huang, JinqingNature Communications (2021), 12 (1), 1292CODEN: NCAOBW; ISSN:2041-1723. (Nature Research)Surface-enhanced Raman spectroscopy (SERS) has emerged as a powerful tool to detect biomols. in aq. environments. However, it is challenging to identify protein structures at low concns., esp. for the proteins existing in an equil. mixt. of various conformations. Here, we develop an in situ optical tweezers-coupled Raman spectroscopy to visualize and control the hotspot between two Ag nanoparticle-coated silica beads, generating tunable and reproducible SERS enhancements with single-mol. level sensitivity. This dynamic SERS detection window is placed in a microfluidic flow chamber to detect the passing-by proteins, which precisely characterizes the structures of three globular proteins without perturbation to their native states. Moreover, it directly identifies the structural features of the transient species of alpha-synuclein among its predominant monomers at physiol. concn. of 1μM by reducing the ensemble averaging. Hence, this SERS platform holds the promise to resolve the structural details of dynamic, heterogeneous, and complex biol. systems.
- 288Fu, W.; Chi, H.; Dai, X.; Zhu, H.; Mesias, V. S. D.; Liu, W.; Huang, J. Efficient optical plasmonic tweezer-controlled single-molecule SERS characterization of pH-dependent amylin species in aqueous milieus. Nat. Commun. 2023, 14, 6996, DOI: 10.1038/s41467-023-42812-3Google ScholarThere is no corresponding record for this reference.
- 289McNay, G.; Docherty, F. T.; Graham, D.; Smith, W. E.; Jordan, P.; Padgett, M.; Leach, J.; Sinclair, G.; Monaghan, P. B.; Cooper, J. M. Visual Observations of SERRS from Single Silver-Coated Silica Microparticles within Optical Tweezers. Angew. Chem., Int. Ed. 2004, 43, 2512– 2514, DOI: 10.1002/anie.200352999Google ScholarThere is no corresponding record for this reference.
- 290Bálint, Š.; Kreuzer, M. P.; Rao, S.; Badenes, G.; Miškovský, P.; Petrov, D. Simple Route for Preparing Optically Trappable Probes for Surface-Enhanced Raman Scattering. J. Phys. Chem. C 2009, 113, 17724– 17729, DOI: 10.1021/jp906318nGoogle Scholar290Simple Route for Preparing Optically Trappable Probes for Surface-Enhanced Raman ScatteringBalint, Stefan; Kreuzer, Mark P.; Rao, Satish; Badenes, Goncal; Miskovsky, Pavol; Petrov, DmitriJournal of Physical Chemistry C (2009), 113 (41), 17724-17729CODEN: JPCCCK; ISSN:1932-7447. (American Chemical Society)Surface-enhanced Raman scattering (SERS) has proven to be a powerful technique for a wide range of topics such as chem. anal., materials research, and biol. imaging. In this work, the authors report in detail on the development and characterization of micrometer-sized dielec. beads with metal colloids attached to their surface. The metalized beads were sufficiently transparent enabling optical trapping while the presence of metal islands provided the SERS. This method is fast and simple and is void of complications when compared to the Tollen's test used in previous publications. This highly efficient probe can be placed and scanned with nanometric accuracy near living cells. The process to create such probes is described including discussion of various parameters that are crit. in achieving the desired results. Addnl., their use is demonstrated by detecting low quantities of a drug in aq. soln. and in a cell membrane.
- 291Svedberg, F.; Li, Z.; Xu, H.; Käll, M. Creating Hot Nanoparticle Pairs for Surface-Enhanced Raman Spectroscopy through Optical Manipulation. Nano Lett. 2006, 6, 2639– 2641, DOI: 10.1021/nl062101mGoogle Scholar291Creating Hot Nanoparticle Pairs for Surface-Enhanced Raman Spectroscopy through Optical ManipulationSvedberg, Fredrik; Li, Zhipeng; Xu, Hongxing; Kaell, MikaelNano Letters (2006), 6 (12), 2639-2641CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)We use optical tweezers to move single silver nanoparticles into near-field contact with immobilized particles, forming isolated surface-enhanced Raman spectroscopy (SERS) active Ag particle dimers. The surface-averaged SERS intensity increases by a factor ∼20 upon dimerization. Electrodynamics calcns. indicate that the final approach between the particles is due to "optical binding". The described methodol. may facilitate controlled single mol. SERS anal.
- 292Tong, L.; Righini, M.; Gonzalez, M. U.; Quidant, R.; Käll, M. Optical aggregation of metal nanoparticles in a microfluidic channel for surface-enhanced Raman scattering analysis. Lab Chip 2009, 9, 193– 195, DOI: 10.1039/B813204FGoogle Scholar292Optical aggregation of metal nanoparticles in a microfluidic channel for surface-enhanced Raman scattering analysisTong, Lianming; Righini, Maurizio; Gonzalez, Maria Ujue; Quidant, Romain; Kaell, MikaelLab on a Chip (2009), 9 (2), 193-195CODEN: LCAHAM; ISSN:1473-0197. (Royal Society of Chemistry)Aggregated metal nanoparticles exhibit enhanced localized electromagnetic fields that enable highly sensitive vibrational spectroscopy anal. based on surface-enhanced Raman scattering (SERS). We demonstrate SERS detection of org. analytes adsorbed to optically aggregated silver nanoparticles in a microfluidic device. The combination of optical tweezers and microfluidics technologies paves the way for novel lab-on-a-chip based plasmonic chemo/bio sensors and overcomes two important drawbacks of std. SERS sensing schemes; i.e. the renewal of nanofabricated metallic substrates and the difficulty of avoiding uncontrolled aggregation in metal colloids.
- 293Fazio, B.; D’Andrea, C.; Foti, A.; Messina, E.; Irrera, A.; Donato, M. G.; Villari, V.; Micali, N.; Maragò, O. M.; Gucciardi, P. G. SERS detection of Biomolecules at Physiological pH via aggregation of Gold Nanorods mediated by Optical Forces and Plasmonic Heating. Sci. Rep. 2016, 6, 26952, DOI: 10.1038/srep26952Google Scholar293SERS detection of Biomolecules at Physiological pH via aggregation of Gold Nanorods mediated by Optical Forces and Plasmonic HeatingFazio, Barbara; D'Andrea, Cristiano; Foti, Antonino; Messina, Elena; Irrera, Alessia; Donato, Maria Grazia; Villari, Valentina; Micali, Norberto; Marago, Onofrio M.; Gucciardi, Pietro G.Scientific Reports (2016), 6 (), 26952CODEN: SRCEC3; ISSN:2045-2322. (Nature Publishing Group)Strategies for in-liq. mol. detection via Surface Enhanced Raman Scattering (SERS) are currently based on chem.-driven aggregation or optical trapping of metal nanoparticles in presence of the target mols. Such strategies allow the formation of SERS-active clusters that efficiently embed the mol. at the "hot spots" of the nanoparticles and enhance its Raman scattering by orders of magnitude. Here we report on a novel scheme that exploits the radiation pressure to locally push gold nanorods and induce their aggregation in buffered solns. of biomols., achieving biomol. SERS detection at almost neutral pH. The sensor is applied to detect non-resonant amino acids and proteins, namely Phenylalanine (Phe), Bovine Serum Albumin (BSA) and Lysozyme (Lys), reaching detection limits in the μg/mL range. Being a chem. free and contactless technique, our methodol. is easy to implement, fast to operate, needs small sample vols. and has potential for integration in microfluidic circuits for biomarkers detection.
- 294Lu, W.; Chen, X.; Wang, L.; Li, H.; Fu, Y. V. Combination of an Artificial Intelligence Approach and Laser Tweezers Raman Spectroscopy for Microbial Identification. Anal. Chem. 2020, 92, 6288– 6296, DOI: 10.1021/acs.analchem.9b04946Google Scholar294Combination of an Artificial Intelligence Approach and Laser Tweezers Raman Spectroscopy for Microbial IdentificationLu, Weilai; Chen, Xiuqiang; Wang, Lu; Li, Hanfei; Fu, Yu VincentAnalytical Chemistry (Washington, DC, United States) (2020), 92 (9), 6288-6296CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Raman spectroscopy is a nondestructive, label-free, highly specific approach that provides the chem. information on materials. Thus, it is suitable to be used as an effective anal. tool to characterize biol. samples. Here we introduce a novel method that uses artificial intelligence to analyze biol. Raman spectra and identify the microbes at a single-cell level. The combination of a framework of convolutional neural network (ConvNet) and Raman spectroscopy allows the extn. of the Raman spectral features of a single microbial cell and then categorizes cells according to their spectral features. As the proof of concept, we measured Raman spectra of 14 microbial species at a single-cell level and constructed an optimal ConvNet model using the Raman data. The av. accuracy of classification by ConvNet is 95.64 ± 5.46%. Meanwhile, we introduced an occlusion-based Raman spectra feature extn. to visualize the wts. of Raman features for distinguishing different species.
- 295Shang, L.; Liang, P.; Xu, L.; Xue, Y.; Liu, K.; Wang, Y.; Bao, X.; Chen, F.; Peng, H.; Wang, Y.; Ju, J.; Li, B. Stable SERS Detection of Lactobacillus fermentum Using Optical Tweezers in a Microfluidic Environment. Anal. Chem. 2024, 96, 248– 255, DOI: 10.1021/acs.analchem.3c03852Google ScholarThere is no corresponding record for this reference.
- 296Kitahama, Y.; Funaoka, M.; Ozaki, Y. Plasmon-Enhanced Optical Tweezers for Single Molecules on and near a Colloidal Silver Nanoaggregate. J. Phys. Chem. C 2019, 123, 18001– 18006, DOI: 10.1021/acs.jpcc.9b05626Google Scholar296Plasmon-Enhanced Optical Tweezers for Single Molecules on and near a Colloidal Silver NanoaggregateKitahama, Yasutaka; Funaoka, Misato; Ozaki, YukihiroJournal of Physical Chemistry C (2019), 123 (29), 18001-18006CODEN: JPCCCK; ISSN:1932-7447. (American Chemical Society)At the junction of an Ag nanoaggregate, single mols. can emit surface-enhanced Raman scattering and fluorescence (SERS and SEF) and can be optically trapped by an enhanced electromagnetic field via plasmon resonance. Blinking SERS and SEF from a single mol. on the same nanoaggregate were obsd. simultaneously in a bicolor movie. By super-resoln. imaging, the positions of the SERS- and SEF-active mols. were detected beyond the diffraction limit. The spatial fluctuation of the mol. on the nanoaggregate was suppressed as the excitation laser intensity increased. The reason is that the single mol. was optically trapped at the junction via plasmon resonance because the mislocalization effect and the signal intensity do not influence a change in the spatial fluctuation in the super-resoln. imaging. The spatial fluctuation of the SEF-active mol. near the Ag surface was larger than that of the SERS-active mol. adsorbed on the surface. The power spectral d. revealed that the plasmon-enhanced optically trapped mol. by excitation at high laser intensity moved randomly rather than harmonically.
- 297Oyamada, N.; Minamimoto, H.; Murakoshi, K. Room-Temperature Molecular Manipulation via Plasmonic Trapping at Electrified Interfaces. J. Am. Chem. Soc. 2022, 144, 2755– 2764, DOI: 10.1021/jacs.1c12213Google Scholar297Room-Temperature Molecular Manipulation via Plasmonic Trapping at Electrified InterfacesOyamada, Nobuaki; Minamimoto, Hiro; Murakoshi, KeiJournal of the American Chemical Society (2022), 144 (6), 2755-2764CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)For the motion control of individual mols. at room temp., optical tweezers could be one of the best approaches to realize desirable selectivity with high resoln. in time and space. Because of phys. limitations due to the thermal fluctuation, optical manipulation of small mols. at room temp. is still a challenging subject. The difficulty of the manipulation also emerged from the variation of mol. polarizability depending on the choice of mols. as well as the mol. orientation to the optical field. In this article, we have demonstrated plasmonic optical trapping of small size mols. with less than 1 nm at the gap of a single metal nanodimer immersed in an electrolyte soln. In situ electrochem. surface-enhanced Raman scattering measurements prove that a plasmonic structure under electrochem. potential control realizes not only the selective mol. condensation but also the formation of unique mixed mol. phases which is distinct from those under a thermodn. equil. Through detailed analyses of optical trapping behavior, we established the methodol. of plasmonic optical trapping to create the novel adsorption isotherm under applying an optical force at electrified interfaces.
- 298Yang, W.; van Dijk, M.; Primavera, C.; Dekker, C. FIB-milled plasmonic nanoapertures allow for long trapping times of individual proteins. iScience 2021, 24, 103237, DOI: 10.1016/j.isci.2021.103237Google Scholar298FIB-milled plasmonic nanoapertures allow for long trapping times of individual proteinsYang, Wayne; van Dijk, Madeleine; Primavera, Christian; Dekker, CeesiScience (2021), 24 (11), 103237CODEN: ISCICE; ISSN:2589-0042. (Elsevier B.V.)We have developed a fabrication methodol. for label-free optical trapping of individual nanobeads and proteins in inverted-bowtie-shaped plasmonic gold nanopores. Arrays of these nanoapertures can be reliably produced using focused ion beam (FIB) milling with gap sizes of 10-20 nm, single-nanometer variation, and with a remarkable stability that allows for repeated use. We employ an optical readout where the presence of the protein entering the trap is marked by an increase in the transmission of light through the nanoaperture from the shift of the plasmonic resonance. In addn., the optical trapping force of the plasmonic nanopores allows 20-nm polystyrene beads and proteins, such as beta-amylase and Heat Shock Protein (HSP90), to be trapped for very long times (approx. minutes). On demand, we can release the trapped mol. for another protein to be interrogated. Our work opens up new routes to acquire information on the conformation and dynamics of individual proteins.
- 299Hernández-Sarria, J. J.; Oliveira, O. N.; Mejía-Salazar, J. R. Toward Lossless Infrared Optical Trapping of Small Nanoparticles Using Nonradiative Anapole Modes. Phys. Rev. Lett. 2021, 127, 186803, DOI: 10.1103/PhysRevLett.127.186803Google Scholar299Toward Lossless Infrared Optical Trapping of Small Nanoparticles Using Nonradiative Anapole ModesHernandez-Sarria, J. J.; Oliveira, Jr., Osvaldo N.; Mejia-Salazar, J. R.Physical Review Letters (2021), 127 (18), 186803CODEN: PRLTAO; ISSN:1079-7114. (American Physical Society)A challenge in plasmonic trapping of small nanoparticles is the heating due to the Joule effect of metallic components. This heating can be avoided with electromagnetic field confinement in high-refractive-index materials, but nanoparticle trapping is difficult because the electromagnetic fields are mostly confined inside the dielec. nanostructures. Herein, we present the design of an all-dielec. platform to capture small dielec. nanoparticles without heating the nanostructure. It consists of a Si nanodisk engineered to exhibit the second-order anapole mode at the IR regime (λ=980 nm), where Si has negligible losses, with a slot at the center. A strong electromagnetic hot spot is created, thus allowing us to capture nanoparticles as small as 20 nm. The numerical calcns. indicate that optical trapping in these all-dielec. nanostructures occurs without heating only in the IR, since for visible wavelengths the heating levels are similar to those in plasmonic nanostructures.
- 300Hernandez-Sarria, J. J.; Oliveira, O. N., Jr; Mejía-Salazar, J. R. Numerical simulations of double-well optical potentials in all-dielectric nanostructures for manipulation of small nanoparticles in aqueous media. ACS Applied Nano Materials 2023, 6, 1405– 1412, DOI: 10.1021/acsanm.2c05047Google ScholarThere is no corresponding record for this reference.
- 301Hong, I.; Hong, C.; Tutanov, O. S.; Massick, C.; Castleberry, M.; Zhang, Q.; Jeppesen, D. K.; Higginbotham, J. N.; Franklin, J. L.; Vickers, K.; Coffey, R. J.; Ndukaife, J. C. Anapole-Assisted Low-Power Optical Trapping of Nanoscale Extracellular Vesicles and Particles. Nano Lett. 2023, 23, 7500– 7507, DOI: 10.1021/acs.nanolett.3c02014Google Scholar301Anapole-Assisted Low-Power Optical Trapping of Nanoscale Extracellular Vesicles and ParticlesHong, Ikjun; Hong, Chuchuan; Tutanov, Oleg S.; Massick, Clark; Castleberry, Mark; Zhang, Qin; Jeppesen, Dennis K.; Higginbotham, James N.; Franklin, Jeffrey L.; Vickers, Kasey; Coffey, Robert J.; Ndukaife, Justus C.Nano Letters (2023), 23 (16), 7500-7507CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)This study addresses the challenge of trapping nanoscale biol. particles using optical tweezers without the photothermal heating effect and the limitation presented by the diffraction limit. Optical tweezers are effective for trapping microscopic biol. objects but not for nanoscale specimens due to the diffraction limit. To overcome this, we present an approach that uses optical anapole states in all-dielec. nanoantenna systems on distributed Bragg reflector substrates to generate strong optical gradient force and potential on nanoscale biol. objects with negligible temp. rise below 1 K. The anapole antenna condenses the accessible electromagnetic energy to scales as small as 30 nm. Using this approach, we successfully trapped nanosized extracellular vesicles and supermeres (approx. 25 nm in size) using low laser power of only 10.8 mW. This nanoscale optical trapping platform has great potential for single mol. anal. while precluding photothermal degrdn.
- 302Conteduca, D.; Brunetti, G.; Barth, I.; Quinn, S. D.; Ciminelli, C.; Krauss, T. F. Multiplexed Near-Field Optical Trapping Exploiting Anapole States. ACS Nano 2023, 17, 16695– 16702, DOI: 10.1021/acsnano.3c03100Google ScholarThere is no corresponding record for this reference.
- 303Zhang, R.; Zhang, Y.; Dong, Z. C.; Jiang, S.; Zhang, C.; Chen, L. G.; Zhang, L.; Liao, Y.; Aizpurua, J.; Luo, Y.; Yang, J. L.; Hou, J. G. Chemical mapping of a single molecule by plasmon-enhanced Raman scattering. Nature 2013, 498, 82– 86, DOI: 10.1038/nature12151Google Scholar303Chemical mapping of a single molecule by plasmon-enhanced Raman scatteringZhang, R.; Zhang, Y.; Dong, Z. C.; Jiang, S.; Zhang, C.; Chen, L. G.; Zhang, L.; Liao, Y.; Aizpurua, J.; Luo, Y.; Yang, J. L.; Hou, J. G.Nature (London, United Kingdom) (2013), 498 (7452), 82-86CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)Visualizing individual mols. with chem. recognition is a longstanding target in catalysis, mol. nanotechnol. and biotechnol. Mol. vibrations provide a valuable fingerprint' for such identification. Vibrational spectroscopy based on tip-enhanced Raman scattering allows us to access the spectral signals of mol. species very efficiently via the strong localized plasmonic fields produced at the tip apex. However, the best spatial resoln. of the tip-enhanced Raman scattering imaging is still limited to 3-15 nm, which is not adequate for resolving a single mol. chem. Here we demonstrate Raman spectral imaging with spatial resoln. below one nanometer, resolving the inner structure and surface configuration of a single mol. This is achieved by spectrally matching the resonance of the nanocavity plasmon to the mol. vibronic transitions, particularly the downward transition responsible for the emission of Raman photons. This matching is made possible by the extremely precise tuning capability provided by scanning tunneling microscopy. Exptl. evidence suggests that the highly confined and broadband nature of the nanocavity plasmon field in the tunnelling gap is essential for ultrahigh-resoln. imaging through the generation of an efficient double-resonance enhancement for both Raman excitation and Raman emission. Our technique not only allows for chem. imaging at the single-mol. level, but also offers a new way to study the optical processes and photochem. of a single mol.
- 304Jaculbia, R. B.; Imada, H.; Miwa, K.; Iwasa, T.; Takenaka, M.; Yang, B.; Kazuma, E.; Hayazawa, N.; Taketsugu, T.; Kim, Y. Single-molecule resonance Raman effect in a plasmonic nanocavity. Nat. Nanotechnol. 2020, 15, 105– 110, DOI: 10.1038/s41565-019-0614-8Google Scholar304Single-molecule resonance Raman effect in a plasmonic nanocavityJaculbia, Rafael B.; Imada, Hiroshi; Miwa, Kuniyuki; Iwasa, Takeshi; Takenaka, Masato; Yang, Bo; Kazuma, Emiko; Hayazawa, Norihiko; Taketsugu, Tetsuya; Kim, YousooNature Nanotechnology (2020), 15 (2), 105-110CODEN: NNAABX; ISSN:1748-3387. (Nature Research)Tip-enhanced Raman spectroscopy (TERS) is a versatile tool for chem. anal. at the nanoscale. In earlier TERS expts., Raman modes with components parallel to the tip were studied based on the strong elec. field enhancement along the tip. Perpendicular modes were usually neglected. Here, we investigate an isolated copper naphthalocyanine mol. adsorbed on a triple-layer NaCl on Ag(111) using scanning tunnelling microscope TERS imaging. For flat-lying mols. on NaCl, the Raman images present different patterns depending on the symmetry of the vibrational mode. Our results reveal that components of the elec. field perpendicular to the tip should be considered aside from the parallel components. Moreover, under resonance excitation conditions, the perpendicular components can play a substantial role in the enhancement. This single-mol. study in a well-defined environment provides insights into the Raman process at the plasmonic nanocavity, which may be useful in the nanoscale metrol. of various mol. systems.
- 305Benz, F.; Tserkezis, C.; Herrmann, L. O.; de Nijs, B.; Sanders, A.; Sigle, D. O.; Pukenas, L.; Evans, S. D.; Aizpurua, J.; Baumberg, J. J. Nanooptics of Molecular-Shunted Plasmonic Nanojunctions. Nano Lett. 2015, 15, 669– 674, DOI: 10.1021/nl5041786Google Scholar305Nanooptics of Molecular-Shunted Plasmonic NanojunctionsBenz, Felix; Tserkezis, Christos; Herrmann, Lars O.; de Nijs, Bart; Sanders, Alan; Sigle, Daniel O.; Pukenas, Laurynas; Evans, Stephen D.; Aizpurua, Javier; Baumberg, Jeremy J.Nano Letters (2015), 15 (1), 669-674CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)Gold nanoparticles are sepd. above a planar gold film by 1.1 nm thick self-assembled mol. monolayers of different conductivities. Incremental replacement of the nonconductive mols. with a chem. equiv. conductive version differing by only one atom produces a strong 50 nm blue-shift of the coupled plasmon. With modeling this gives a conductance of 0.17G0 per biphenyl-4,4'-dithiol mol. and a total conductance across the plasmonic junction of 30G0. Our approach provides a reliable tool quantifying the no. of mols. in each plasmonic hotspot, here <200.
- 306Li, L.; Hutter, T.; Steiner, U.; Mahajan, S. Single molecule SERS and detection of biomolecules with a single gold nanoparticle on a mirror junction. Analyst 2013, 138, 4574– 4578, DOI: 10.1039/c3an00447cGoogle Scholar306Single molecule SERS and detection of biomolecules with a single gold nanoparticle on a mirror junctionLi, Li; Hutter, Tanya; Steiner, Ullrich; Mahajan, SumeetAnalyst (Cambridge, United Kingdom) (2013), 138 (16), 4574-4578CODEN: ANALAO; ISSN:0003-2654. (Royal Society of Chemistry)Using the bianalyte method we unambiguously demonstrate that a single gold nanosphere on a metal film junction, in the so-called nanoparticle on a mirror configuration, is capable of single mol. detection with surface-enhanced Raman spectroscopy (SERS). Also this configuration serves as a convenient and highly sensitive SERS sensor for detection of biomols. Such simple nano-junction based systems are ideal for chem. and biomedical anal.
- 307Zhang, Y.; Zhen, Y.-R.; Neumann, O.; Day, J. K.; Nordlander, P.; Halas, N. J. Coherent anti-Stokes Raman scattering with single-molecule sensitivity using a plasmonic Fano resonance. Nat. Commun. 2014, 5, 4424, DOI: 10.1038/ncomms5424Google Scholar307Coherent anti-Stokes Raman scattering with single-molecule sensitivity using a plasmonic Fano resonanceZhang, Yu; Zhen, Yu-Rong; Neumann, Oara; Day, Jared K.; Nordlander, Peter; Halas, Naomi J.Nature Communications (2014), 5 (), 4424CODEN: NCAOBW; ISSN:2041-1723. (Nature Publishing Group)Plasmonic nanostructures are of particular interest as substrates for the spectroscopic detection and identification of individual mols. Single-mol. sensitivity Raman detection has been achieved by combining resonant mol. excitation with large electromagnetic field enhancements experienced by a mol. assocd. with an interparticle junction. Detection of mols. with extremely small Raman cross-sections (∼10-30 cm2 sr-1), however, has remained elusive. Here we show that coherent anti-Stokes Raman spectroscopy (CARS), a nonlinear spectroscopy of great utility and potential for mol. sensing, can be used to obtain single-mol. detection sensitivity, by exploiting the unique light harvesting properties of plasmonic Fano resonances. The CARS signal is enhanced by ∼11 orders of magnitude relative to spontaneous Raman scattering, enabling the detection of single mols., which is verified using a statistically rigorous bi-analyte method. This approach combines unprecedented single-mol. spectral sensitivity with plasmonic substrates that can be fabricated using top-down lithog. strategies.
- 308Lim, D.-K.; Jeon, K.-S.; Kim, H. M.; Nam, J.-M.; Suh, Y. D. Nanogap-engineerable Raman-active nanodumbbells for single-molecule detection. Nat. Mater. 2010, 9, 60– 67, DOI: 10.1038/nmat2596Google Scholar308Nanogap-engineerable Raman-active nanodumbbells for single-molecule detectionLim, Dong-Kwon; Jeon, Ki-Seok; Kim, Hyung Min; Nam, Jwa-Min; Suh, Yung DougNature Materials (2010), 9 (1), 60-67CODEN: NMAACR; ISSN:1476-1122. (Nature Publishing Group)Surface-enhanced Raman scattering (SERS)-based signal amplification and detection methods using plasmonic nanostructures have been widely investigated for imaging and sensing applications. However, SERS-based mol. detection strategies have not been practically useful because there is no straightforward method to synthesize and characterize highly sensitive SERS-active nanostructures with sufficiently high yield and efficiency, which results in an extremely low cross-section area in Raman sensing. Here, the authors report a high-yield synthetic method for SERS-active gold-silver core-shell nanodumbbells, where the gap between two nanoparticles and the Raman-dye position and environment can be engineered on the nanoscale. Atomic-force-microscope-correlated nano-Raman measurements of individual dumbbell structures demonstrate that Raman signals can be repeatedly detected from single-DNA-tethered nanodumbbells. These programmed nanostructure fabrication and single-DNA detection strategies open avenues for the high-yield synthesis of optically active smart nanoparticles and structurally reproducible nanostructure-based single-mol. detection and bioassays.
- 309Liu, S.-C.; Xie, B.-K.; Zhong, C.-B.; Wang, J.; Ying, Y.-L.; Long, Y.-T. An advanced optical–electrochemical nanopore measurement system for single-molecule analysis. Rev. Sci. Instrum. 2021, 92, 121301, DOI: 10.1063/5.0067185Google Scholar309An advanced optical-electrochemical nanopore measurement system for single-molecule analysisLiu, Shao-Chuang; Xie, Bao-Kang; Zhong, Cheng-Bing; Wang, Jia; Ying, Yi-Lun; Long, Yi-TaoReview of Scientific Instruments (2021), 92 (12), 121301CODEN: RSINAK; ISSN:0034-6748. (American Institute of Physics)Nanopore measurement has advanced in single-mol. anal. by providing a transient time and confined space window that only allows one interested mol. to exist. By optimization and integration of the elec. and optical anal. strategies in this transient window, the acquisition of comprehensive information could be achieved to resolve the intrinsic properties and heterogeneity of a single mol. In this work, we present a roadmap to build a unified optical and electrochem. synchronous measurement platform for the research of a single mol. We design a low-cost ultralow-current amplifier with low noise and high-bandwidth to measure the ionic current events as a single mol. translocates through a nanopore and combine a multi-functional optical system to implement the acquisition of the fluorescence, scattering spectrum, and photocurrent intensity of single mol. events in a nanopore confined space. Our system is a unified and unique platform for the protein nanopore, the solid-state nanopore, and the glass capillary nanopore, which has advantages in the comprehensive research of nanopore single-mol. techniques. (c) 2021 American Institute of Physics.
- 310Belkin, M.; Chao, S.-H.; Jonsson, M. P.; Dekker, C.; Aksimentiev, A. Plasmonic Nanopores for Trapping, Controlling Displacement, and Sequencing of DNA. ACS Nano 2015, 9, 10598– 10611, DOI: 10.1021/acsnano.5b04173Google Scholar310Plasmonic nanopores for trapping, controlling displacement, and sequencing of DNABelkin, Maxim; Chao, Shu-Han; Jonsson, Magnus P.; Dekker, Cees; Aksimentiev, AlekseiACS Nano (2015), 9 (11), 10598-10611CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)With the aim of developing a DNA sequencing methodol., we theor. examine the feasibility of using nanoplasmonics to control the translocation of a DNA mol. through a solid-state nanopore and to read off sequence information using surface-enhanced Raman spectroscopy. Using mol. dynamics simulations, we show that high-intensity optical hot spots produced by a metallic nanostructure can arrest DNA translocation through a solid-state nanopore, thus providing a phys. knob for controlling the DNA speed. Switching the plasmonic field on and off can displace the DNA mol. in discrete steps, sequentially exposing neighboring fragments of a DNA mol. to the pore as well as to the plasmonic hot spot. Surface-enhanced Raman scattering from the exposed DNA fragments contains information about their nucleotide compn., possibly allowing the identification of the nucleotide sequence of a DNA mol. transported through the hot spot. The principles of plasmonic nanopore sequencing can be extended to detection of DNA modifications and RNA characterization.
- 311Shi, X.; Verschueren, D.; Pud, S.; Dekker, C. Integrating Sub-3 nm Plasmonic Gaps into Solid-State Nanopores. Small 2018, 14, 1703307, DOI: 10.1002/smll.201703307Google ScholarThere is no corresponding record for this reference.
- 312Shi, X.; Verschueren, D. V.; Dekker, C. Active Delivery of Single DNA Molecules into a Plasmonic Nanopore for Label-Free Optical Sensing. Nano Lett. 2018, 18, 8003– 8010, DOI: 10.1021/acs.nanolett.8b04146Google Scholar312Active Delivery of Single DNA Molecules into a Plasmonic Nanopore for Label-Free Optical SensingShi, Xin; Verschueren, Daniel V.; Dekker, CeesNano Letters (2018), 18 (12), 8003-8010CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)Plasmon resonance biosensors provide ultimate sensitivity at the single-mol. level. This sensitivity is, however, assocd. with a nanometer-sized confined hotspot, and mol. transport toward the sensor relies on inefficient diffusion. Here, the authors combine a plasmonic nanoantenna with a solid-state nanopore and demonstrate that single DNA mols. can be efficiently delivered to the plasmonic hotspots and detected in a label-free manner at submillisecond acquisition rates by monitoring the backscattered light intensity from the plasmonic nanoantennas. The method realizes a better than 200 μs temporal resoln. together with a down to subsecond waiting time, which is orders of magnitude better than traditional single-mol. plasmonic resonance sensing methods. Furthermore, the elec. field applied to the nanopore can actively drive biomols. away from the hotspot, preventing mols. to permanently bind to the gold sensor surface and allowing efficient reuse of the sensor. The plasmonic nanopore sensor thus significantly outperforms conventional plasmon resonance sensors and provides great opportunities for high-throughput optical single-mol.-sensing assays.
- 313Li, W.; Zhou, J.; Maccaferri, N.; Krahne, R.; Wang, K.; Garoli, D. Enhanced Optical Spectroscopy for Multiplexed DNA and Protein-Sequencing with Plasmonic Nanopores: Challenges and Prospects. Anal. Chem. 2022, 94, 503– 514, DOI: 10.1021/acs.analchem.1c04459Google Scholar313Enhanced Optical Spectroscopy for Multiplexed DNA and Protein-Sequencing with Plasmonic Nanopores: Challenges and ProspectsLi, Wang; Zhou, Juan; Maccaferri, Nicolo; Krahne, Roman; Wang, Kang; Garoli, DenisAnalytical Chemistry (Washington, DC, United States) (2022), 94 (2), 503-514CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)A review. Nanopore sequencing is currently a widely used technol. for single-mol. DNA detection and anal. Although the error rate is still too high to enable diagnostic applications, biol. nanopores have demonstrated to be able to read the sequence of single DNA mol., and massive efforts are now ongoing to exploit the same technol. for decoding single proteins. In this framework, solid-state nanopore-based sensors have emerged as alternative platforms for single-mol. sequencing. They did not demonstrate yet to enable reliable DNA sequencing, but they can be easily engineered to include addnl. functionalities, such as mech. robustness and versatile chem. functionalization. Among the different classes of solid-state nanopores, plasmonic nanopores have rapidly attracted the interest within the nanopore community, since they allow to engineer the electromagnetic field, which can be exploited as an advanced tool for enhanced optical spectroscopy and tweezing, as well as local control over temp. More importantly, plasmonic nanopores are the most versatile platform to realize electro-optical single-mol. detection and to explore integrated sequencing methods. In particular, the use of optical read-out in single-mol. sequencing is a key aspect to tackle the challenging goal of protein sequencing, a goal that is more than challenging to achieve using elec. read-out approaches. This crit. Review offers a comprehensive understanding of the most recent state-of-the-art plasmonic nanopores for single-mol. detection and biomol. sequencing applications, and discusses the latest advances and future perspectives on plasmonic nanopore-based technologies, focusing the discussion on the crit. aspects to be overcome to enable multiplexing anal. of DNA and protein with single-mol. sensitivity.
- 314Hubarevich, A.; Huang, J.-A.; Giovannini, G.; Schirato, A.; Zhao, Y.; Maccaferri, N.; De Angelis, F.; Alabastri, A.; Garoli, D. λ-DNA through Porous Materials─Surface-Enhanced Raman Scattering in a Simple Plasmonic Nanopore. J. Phys. Chem. C 2020, 124, 22663– 22670, DOI: 10.1021/acs.jpcc.0c06165Google Scholar314λ-DNA through Porous Materials-Surface-Enhanced Raman Scattering in a Simple Plasmonic NanoporeHubarevich, Aliaksandr; Huang, Jian-An; Giovannini, Giorgia; Schirato, Andrea; Zhao, Yingqi; Maccaferri, Nicolo; De Angelis, Francesco; Alabastri, Alessandro; Garoli, DenisJournal of Physical Chemistry C (2020), 124 (41), 22663-22670CODEN: JPCCCK; ISSN:1932-7447. (American Chemical Society)Engineered electromagnetic fields in plasmonic nanopores enable enhanced optical detection for single-mol. sensing and sequencing. Here, a plasmonic nanopore prepd. in a thick nanoporous film was used to study, by surface-enhanced Raman spectroscopy, the interaction between the metallic surface of the pore and a long-chain double-strand DNA mol. free to diffuse through the pore. How the matrix of the porous material can interact with the mol. thanks to: (1) transient aspecific interactions between the porous surface and DNA; (2) diffusion; and (3) thermal and optical forces exerted by the localized field in a metallic nanostructure on the DNA mol are discussed. An interaction time up to tens of milliseconds enables the authors to collect high signal-to-noise Raman signatures, allowing an easy label-free reading of information from the DNA mol. Moreover, to increase the rate of detection, the authors tested a polymeric porous hydrogel placed beneath the solid-state membrane. The hydrogel enables a slowdown of the mol. diffusion time, thus increasing the no. of detected interaction events by a factor 20. The anal. of the obsd. Raman peaks and their relative intensities, combined with theor. simulations, allows the authors to get further information on the process of translocation and the folding state and orientation of the translocating mol. The authors' results demonstrate temporary adsorption of the DNA mol. on the porous material during the translocation due to the diffusion force. Finally, the authors provide a qual. evaluation of the nucleotides' contents in the different groups of collected signal. The proposed approach can find interesting applications not only in DNA sensing and sequencing but also on generic nanopore spectroscopy.
- 315Assad, O. N.; Gilboa, T.; Spitzberg, J.; Juhasz, M.; Weinhold, E.; Meller, A. Light-Enhancing Plasmonic-Nanopore Biosensor for Superior Single-Molecule Detection. Adv. Mater. 2017, 29, 1605442, DOI: 10.1002/adma.201605442Google ScholarThere is no corresponding record for this reference.
- 316Zhao, Y.; Hubarevich, A.; De Fazio, A. F.; Iarossi, M.; Huang, J.-A.; De Angelis, F. Plasmonic Bowl-Shaped Nanopore for Raman Detection of Single DNA Molecules in Flow-Through. Nano Lett. 2023, 23, 4830– 4836, DOI: 10.1021/acs.nanolett.3c00340Google Scholar316Plasmonic Bowl-Shaped Nanopore for Raman Detection of Single DNA Molecules in Flow-ThroughZhao, Yingqi; Hubarevich, Aliaksandr; De Fazio, Angela Federica; Iarossi, Marzia; Huang, Jian-An; De Angelis, FrancescoNano Letters (2023), 23 (11), 4830-4836CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)A review. Plasmonic nanopores combined with Raman spectroscopy are emerging as platforms for single-mol. detection and sequencing in label-free mode. Recently, the ability of identifying single DNA bases or amino acids has been demonstrated for mols. adsorbed on plasmonic particles and then delivered into the plasmonic pores. Here, we report on bowl-shaped plasmonic gold nanopores capable of direct Raman detection of single λ-DNA mols. in a flow-through scheme. The bowl shape enables the incident laser to be focused into the nanopore to generate a single intense hot spot with no cut off in pore size. Therefore, we achieved ultrasmall focusing of NIR light in a spot of 3 nm. This enabled us to detect 7 consecutive bases along the DNA chain in flow-through conditions. Furthermore, we found a novel electrofluidic mechanism to manipulate the mol. trajectory within the pore vol. so that the mol. is pushed toward the hot spot, thus improving the detection efficiency.
- 317Shen, Q.; Zhou, P.-L.; Huang, B.-T.; Zhou, J.; Liu, H.-L.; Ahmed, S. A.; Ding, X.-L.; Li, J.; Zhai, Y.-M.; Wang, K. Mass transport through a sub-10 nm single gold nanopore: SERS and ionic current measurement. J. Electroanal. Chem. 2021, 894, 115373, DOI: 10.1016/j.jelechem.2021.115373Google Scholar317Mass transport through a sub-10 nm single gold nanopore: SERS and ionic current measurementShen, Qi; Zhou, Pan-Ling; Huang, Bin-Tong; Zhou, Juan; Liu, Hai-Ling; Ahmed, Saud Asif; Ding, Xin-Lei; Li, Jian; Zhai, Yue-Ming; Wang, KangJournal of Electroanalytical Chemistry (2021), 894 (), 115373CODEN: JECHES; ISSN:1873-2569. (Elsevier B.V.)Au nanopore is promising to be used in single mol. sequencing by measuring surface enhanced Raman scattering (SERS) spectrum. To achieve this goal, fabrication of small and size-controllable single Au nanopore is in urgent need. The authors synthesized Au nanoplates with a sub-10 nm single nanopore at the center, which was then successfully attached at the tip of a glass nanopipette using sulfhydryl silane. The transport of ∼1.4 × 103 rhodamine 6G mols. was detected using SERS. The current blockage caused by single lambda DNA passing through the nanopore was also obsd. The translocation time of lambda DNA through the Au nanopore was much longer than that of lambda DNA through the bare glass nanopipette, revealing the strong DNA-Au nanopore interaction affected the transport behavior of lambda DNA. The obsd. result further shows that the time resoln. of SERS ( approx. ms) may match the transport time of DNA through plasmonic nanopore. The sub-10 nm Au nanopore is possible to be used in single mol. transport detection with the improvement of the nanopore attachment.
- 318Cao, J.; Liu, H.-L.; Yang, J.-M.; Li, Z.-Q.; Yang, D.-R.; Ji, L.-N.; Wang, K.; Xia, X.-H. SERS Detection of Nucleobases in Single Silver Plasmonic Nanopores. ACS Sens. 2020, 5, 2198– 2204, DOI: 10.1021/acssensors.0c00844Google Scholar318SERS Detection of Nucleobases in Single Silver Plasmonic NanoporesCao, Jiao; Liu, Hai-Ling; Yang, Jin-Mei; Li, Zhong-Qiu; Yang, Dong-Rui; Ji, Li-Na; Wang, Kang; Xia, Xing-HuaACS Sensors (2020), 5 (7), 2198-2204CODEN: ASCEFJ; ISSN:2379-3694. (American Chemical Society)Conventional ion current-based nanopore techniques that identify single mols. are hampered by limitations of providing only the ionic current information. Here, the authors introduce a silver nanotriangle-based nanopore (diam. < 50 nm) system for detecting mol. translocation using surface-enhanced Raman scattering. Rhodamine 6G was used as a model mol. to study the effect of an elec. field (-1 V) on the mass transport. The four DNA bases also show significantly different SERS signals when they are transported into the plasmonic nanopore. The observations suggest that in the elec. field, analyte mols. are driven into the nanopipette through the hot spot of the silver nanopore. The plasmonic nanopore shows great potential as a highly sensitive SERS platform for detecting mol. transport and paves the way for single mol. probing.
- 319Zhou, J.; Lan, Q.; Li, W.; Ji, L.-N.; Wang, K.; Xia, X.-H. Single Molecule Protein Segments Sequencing by a Plasmonic Nanopore. Nano Lett. 2023, 23, 2800– 2807, DOI: 10.1021/acs.nanolett.3c00086Google ScholarThere is no corresponding record for this reference.
- 320Shendure, J.; Balasubramanian, S.; Church, G. M.; Gilbert, W.; Rogers, J.; Schloss, J. A.; Waterston, R. H. DNA sequencing at 40: past, present and future. Nature 2017, 550, 345– 353, DOI: 10.1038/nature24286Google Scholar320DNA sequencing at 40: past, present and futureShendure, Jay; Balasubramanian, Shankar; Church, George M.; Gilbert, Walter; Rogers, Jane; Schloss, Jeffery A.; Waterston, Robert H.Nature (London, United Kingdom) (2017), 550 (7676), 345-353CODEN: NATUAS; ISSN:0028-0836. (Nature Research)This review commemorates the 40th anniversary of DNA sequencing, a period in which we have already witnessed multiple technol. revolutions and a growth in scale from a few kilobases to the first human genome, and now to millions of human and a myriad of other genomes. DNA sequencing has been extensively and creatively repurposed, including as a 'counter' for a vast range of mol. phenomena. We predict that in the long view of history, the impact of DNA sequencing will be on a par with that of the microscope.
- 321Alfaro, J. A.; Bohlander, P.; Dai, M.; Filius, M.; Howard, C. J.; van Kooten, X. F.; Ohayon, S.; Pomorski, A.; Schmid, S.; Aksimentiev, A.; Anslyn, E. V.; Bedran, G.; Cao, C.; Chinappi, M.; Coyaud, E.; Dekker, C.; Dittmar, G.; Drachman, N.; Eelkema, R.; Goodlett, D.; Hentz, S.; Kalathiya, U.; Kelleher, N. L.; Kelly, R. T.; Kelman, Z.; Kim, S. H.; Kuster, B.; Rodriguez-Larrea, D.; Lindsay, S.; Maglia, G.; Marcotte, E. M.; Marino, J. P.; Masselon, C.; Mayer, M.; Samaras, P.; Sarthak, K.; Sepiashvili, L.; Stein, D.; Wanunu, M.; Wilhelm, M.; Yin, P.; Meller, A.; Joo, C. The emerging landscape of single-molecule protein sequencing technologies. Nat. Methods 2021, 18, 604– 617, DOI: 10.1038/s41592-021-01143-1Google Scholar321The emerging landscape of single-molecule protein sequencing technologiesAlfaro, Javier Antonio; Bohlander, Peggy; Dai, Mingjie; Filius, Mike; Howard, Cecil J.; van Kooten, Xander F.; Ohayon, Shilo; Pomorski, Adam; Schmid, Sonja; Aksimentiev, Aleksei; Anslyn, Eric V.; Bedran, Georges; Cao, Chan; Chinappi, Mauro; Coyaud, Etienne; Dekker, Cees; Dittmar, Gunnar; Drachman, Nicholas; Eelkema, Rienk; Goodlett, David; Hentz, Sebastien; Kalathiya, Umesh; Kelleher, Neil L.; Kelly, Ryan T.; Kelman, Zvi; Kim, Sung Hyun; Kuster, Bernhard; Rodriguez-Larrea, David; Lindsay, Stuart; Maglia, Giovanni; Marcotte, Edward M.; Marino, John P.; Masselon, Christophe; Mayer, Michael; Samaras, Patroklos; Sarthak, Kumar; Sepiashvili, Lusia; Stein, Derek; Wanunu, Meni; Wilhelm, Mathias; Yin, Peng; Meller, Amit; Joo, ChirlminNature Methods (2021), 18 (6), 604-617CODEN: NMAEA3; ISSN:1548-7091. (Nature Portfolio)Single-cell profiling methods have had a profound impact on the understanding of cellular heterogeneity. While genomes and transcriptomes can be explored at the single-cell level, single-cell profiling of proteomes is not yet established. Here we describe new single-mol. protein sequencing and identification technologies alongside innovations in mass spectrometry that will eventually enable broad sequence coverage in single-cell profiling. These technologies will in turn facilitate biol. discovery and open new avenues for ultrasensitive disease diagnostics.
- 322Zhao, Y. Q.; Iarossi, M.; De Fazio, A. F.; Huang, J. A.; De Angelis, F. Label-Free Optical Analysis of Biomolecules in Solid-State Nanopores: Toward Single-Molecule Protein Sequencing. Acs Photonics 2022, 9, 730– 742, DOI: 10.1021/acsphotonics.1c01825Google Scholar322Label-Free Optical Analysis of Biomolecules in Solid-State Nanopores: Toward Single-Molecule Protein SequencingZhao, Yingqi; Iarossi, Marzia; De Fazio, Angela Federica; Huang, Jian-An; De Angelis, FrancescoACS Photonics (2022), 9 (3), 730-742CODEN: APCHD5; ISSN:2330-4022. (American Chemical Society)Sequence identification of peptides and proteins is central to proteomics. Protein sequencing is mainly conducted by insensitive mass spectroscopy because proteins cannot be amplified, which hampers applications such as single-cell proteomics and precision medicine. The com. success of portable nanopore sequencers for single DNA mols. has inspired extensive research and development of single-mol. techniques for protein sequencing. Among them, three challenges remain: (1) discrimination of the 20 amino acids as building blocks of proteins; (2) unfolding proteins; and (3) controlling the motion of proteins with nonuniformly charged sequences. In this context, the emergence of label-free optical anal. techniques for single amino acids and peptides by solid-state nanopores shows promise for addressing the first challenge. In this Perspective, we first discuss the current challenges of single-mol. fluorescence detection and nanopore resistive pulse sensing in a protein sequencing. Then, label-free optical methods are described to show how they address the single-amino-acid identification within single peptides. They include localized surface plasmon resonance detection and surface-enhanced Raman spectroscopy on plasmonic nanopores. Notably, we report new data to show the ability of plasmon-enhanced Raman scattering to record and discriminate the 20 amino acids at a single-mol. level. In addn., we discuss briefly the manipulation of mol. translocation and liq. flow in plasmonic nanopores for controlling mol. movement to allow high-resoln. reading of protein sequences. We envision that a combination of Raman spectroscopy with plasmonic nanopores can succeed in single-mol. protein sequencing in a label-free way.
- 323Huang, J.-A.; Mousavi, M. Z.; Zhao, Y.; Hubarevich, A.; Omeis, F.; Giovannini, G.; Schütte, M.; Garoli, D.; De Angelis, F. SERS discrimination of single DNA bases in single oligonucleotides by electro-plasmonic trapping. Nat. Commun. 2019, 10, 5321, DOI: 10.1038/s41467-019-13242-xGoogle Scholar323SERS discrimination of single DNA bases in single oligonucleotides by electro-plasmonic trappingHuang Jian-An; Mousavi Mansoureh Z; Zhao Yingqi; Hubarevich Aliaksandr; Omeis Fatima; Giovannini Giorgia; Garoli Denis; De Angelis Francesco; Schutte Moritz; Garoli DenisNature communications (2019), 10 (1), 5321 ISSN:.Surface-enhanced Raman spectroscopy (SERS) sensing of DNA bases by plasmonic nanopores could pave a way to novel methods for DNA analyses and new generation single-molecule sequencing platforms. The SERS discrimination of single DNA bases depends critically on the time that a DNA strand resides within the plasmonic hot spot. In fact, DNA molecules flow through the nanopores so rapidly that the SERS signals collected are not sufficient for single-molecule analysis. Here, we report an approach to control the residence time of molecules in the hot spot by an electro-plasmonic trapping effect. By directly adsorbing molecules onto a gold nanoparticle and then trapping the single nanoparticle in a plasmonic nanohole up to several minutes, we demonstrate single-molecule SERS detection of all four DNA bases as well as discrimination of single nucleobases in a single oligonucleotide. Our method can be extended easily to label-free sensing of single-molecule amino acids and proteins.
- 324Chen, C.; Li, Y.; Kerman, S.; Neutens, P.; Willems, K.; Cornelissen, S.; Lagae, L.; Stakenborg, T.; Van Dorpe, P. High spatial resolution nanoslit SERS for single-molecule nucleobase sensing. Nat. Commun. 2018, 9, 1733, DOI: 10.1038/s41467-018-04118-7Google Scholar324High spatial resolution nanoslit SERS for single-molecule nucleobase sensingChen Chang; Li Yi; Kerman Sarp; Neutens Pieter; Willems Kherim; Cornelissen Sven; Lagae Liesbet; Stakenborg Tim; Van Dorpe Pol; Chen Chang; Kerman Sarp; Neutens Pieter; Lagae Liesbet; Van Dorpe Pol; Li Yi; Cornelissen Sven; Willems KherimNature communications (2018), 9 (1), 1733 ISSN:.Solid-state nanopores promise a scalable platform for single-molecule DNA analysis. Direct, real-time identification of nucleobases in DNA strands is still limited by the sensitivity and the spatial resolution of established ionic sensing strategies. Here, we study a different but promising strategy based on optical spectroscopy. We use an optically engineered elongated nanopore structure, a plasmonic nanoslit, to locally enable single-molecule surface enhanced Raman spectroscopy (SERS). Combining SERS with nanopore fluidics facilitates both the electrokinetic capture of DNA analytes and their local identification through direct Raman spectroscopic fingerprinting of four nucleobases. By studying the stochastic fluctuation process of DNA analytes that are temporarily adsorbed inside the pores, we have observed asynchronous spectroscopic behavior of different nucleobases, both individual and incorporated in DNA strands. These results provide evidences for the single-molecule sensitivity and the sub-nanometer spatial resolution of plasmonic nanoslit SERS.
- 325Li, W.; Guo, L.; Ding, X.; Ding, Y.; Ji, L.; Xia, X.; Wang, K. High-Throughput Single-Molecule Surface-Enhanced Raman Spectroscopic Profiling of Single-Amino Acid Substitutions in Peptides by a Gold Plasmonic Nanopore. ACS Nano 2024, 18, 19200– 19207, DOI: 10.1021/acsnano.4c04775Google ScholarThere is no corresponding record for this reference.
- 326Iarossi, M.; Darvill, D.; Hubarevich, A.; Huang, J.; Zhao, Y.; De Fazio, A.; O’Neill, D.; Tantussi, F.; De Angelis, F. High-Density Plasmonic Nanopores for DNA Sensing at Ultra-Low Concentrations by Plasmon-Enhanced Raman Spectroscopy. Adv. Funct. Mater. 2023, 33, 2301934, DOI: 10.1002/adfm.202301934Google ScholarThere is no corresponding record for this reference.
- 327Huang, J.-A.; Mousavi, M. Z.; Giovannini, G.; Zhao, Y.; Hubarevich, A.; Soler, M. A.; Rocchia, W.; Garoli, D.; De Angelis, F. Multiplexed Discrimination of Single Amino Acid Residues in Polypeptides in a Single SERS Hot Spot. Angew. Chem., Int. Ed. 2020, 59, 11423– 11431, DOI: 10.1002/anie.202000489Google Scholar327Multiplexed Discrimination of Single Amino Acid Residues in Polypeptides in a Single SERS Hot SpotHuang, Jian-An; Mousavi, Mansoureh Z.; Giovannini, Giorgia; Zhao, Yingqi; Hubarevich, Aliaksandr; Soler, Miguel A.; Rocchia, Walter; Garoli, Denis; De Angelis, FrancescoAngewandte Chemie, International Edition (2020), 59 (28), 11423-11431CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)The SERS-based detection of protein sequences with single-residue sensitivity suffers from signal dominance of arom. amino acid residues and backbones, impeding detection of non-arom. amino acid residues. Herein, the authors trap a gold nanoparticle in a plasmonic nanohole to generate a single SERS hot spot for single-mol. detection of 2 similar polypeptides (vasopressin and oxytocin) and 10 distinct amino acids that constitute the 2 polypeptides. Significantly, both arom. and non-arom. amino acids were detected and discriminated at the single-mol. level either at individual amino acid mols. or within the polypeptide chains. Correlated with mol. dynamics simulations, the authors' results suggest that the signal dominance due to large spatial occupancy of arom. rings of the polypeptide sidechains on gold surfaces can be overcome by the high localization of the single hot spot. The superior spectral and spatial discriminative power of the authors' approach can be applied to single-protein anal., fingerprinting, and sequencing.
- 328Ray, T. R.; Choi, J.; Bandodkar, A. J.; Krishnan, S.; Gutruf, P.; Tian, L.; Ghaffari, R.; Rogers, J. A. Bio-Integrated Wearable Systems: A Comprehensive Review. Chem. Rev. 2019, 119, 5461– 5533, DOI: 10.1021/acs.chemrev.8b00573Google Scholar328Bio-Integrated Wearable Systems: A Comprehensive ReviewRay, Tyler R.; Choi, Jungil; Bandodkar, Amay J.; Krishnan, Siddharth; Gutruf, Philipp; Tian, Limei; Ghaffari, Roozbeh; Rogers, John A.Chemical Reviews (Washington, DC, United States) (2019), 119 (8), 5461-5533CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review. Bio-integrated wearable systems can measure a broad range of biophys., biochem., and environmental signals to provide crit. insights into overall health status and to quantify human performance. Recent advances in material science, chem. anal. techniques, device designs, and assembly methods form the foundations for a uniquely differentiated type of wearable technol., characterized by noninvasive, intimate integration with the soft, curved, time-dynamic surfaces of the body. This review summarizes the latest advances in this emerging field of "bio-integrated" technologies in a comprehensive manner that connects fundamental developments in chem., material science, and engineering with sensing technologies that have the potential for widespread deployment and societal benefit in human health care. An introduction to the chemistries and materials for the active components of these systems contextualizes essential design considerations for sensors and assocd. platforms that appear in following sections. The subsequent content highlights the most advanced biosensors, classified according to their ability to capture biophys., biochem., and environmental information. Addnl. sections feature schemes for elec. powering these sensors and strategies for achieving fully integrated, wireless systems. The review concludes with an overview of key remaining challenges and a summary of opportunities where advances in materials chem. will be critically important for continued progress.
- 329Heikenfeld, J.; Jajack, A.; Feldman, B.; Granger, S. W.; Gaitonde, S.; Begtrup, G.; Katchman, B. A. Accessing analytes in biofluids for peripheral biochemical monitoring. Nat. Biotechnol. 2019, 37, 407– 419, DOI: 10.1038/s41587-019-0040-3Google Scholar329Accessing analytes in biofluids for peripheral biochemical monitoringHeikenfeld, Jason; Jajack, Andrew; Feldman, Benjamin; Granger, Steve W.; Gaitonde, Supriya; Begtrup, Gavi; Katchman, Benjamin A.Nature Biotechnology (2019), 37 (4), 407-419CODEN: NABIF9; ISSN:1087-0156. (Nature Research)Peripheral biochem. monitoring involves the use of wearable devices for minimally invasive or noninvasive measurement of analytes in biofluids such as interstitial fluid, saliva, tears and sweat. The goal in most cases is to obtain measurements that serve as surrogates for circulating analyte concns. in blood. Key technol. developments to date include continuous glucose monitors, which use an indwelling sensor needle to measure glucose in interstitial fluid, and device-integrated sweat stimulation for continuous access to analytes in sweat. Further development of continuous sensing technologies through new electrochem. sensing modalities will be a major focus of future research. While there has been much investment in wearable technologies to sense analytes, less effort has been directed to understanding the physiol. of biofluid secretion. Elucidating the underlying biol. is crucial for accelerating technol. progress, as the biofluid itself often presents the greatest challenge in terms of sample vols., secretion rates, filtration, active analyte channels, variable pH and salinity, analyte breakdown and other confounding factors.
- 330Min, J.; Tu, J.; Xu, C.; Lukas, H.; Shin, S.; Yang, Y.; Solomon, S. A.; Mukasa, D.; Gao, W. Skin-Interfaced Wearable Sweat Sensors for Precision Medicine. Chem. Rev. 2023, 123, 5049– 5138, DOI: 10.1021/acs.chemrev.2c00823Google Scholar330Skin-Interfaced Wearable Sweat Sensors for Precision MedicineMin, Jihong; Tu, Jiaobing; Xu, Changhao; Lukas, Heather; Shin, Soyoung; Yang, Yiran; Solomon, Samuel A.; Mukasa, Daniel; Gao, WeiChemical Reviews (Washington, DC, United States) (2023), 123 (8), 5049-5138CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review. Wearable sensors hold great potential in empowering personalized health monitoring, predictive analytics, and timely intervention toward personalized healthcare. Advances in flexible electronics, material sciences, and electrochem. have spurred the development of wearable sweat sensors that enable the continuous and noninvasive screening of analytes indicative of health status. Existing major challenges in wearable sensors include: improving the sweat extn. and sweat sensing capabilities, improving the form factor of the wearable device for minimal discomfort and reliable measurements when worn, and understanding the clin. value of sweat analytes toward biomarker discovery. This review provides a comprehensive review of wearable sweat sensors and outlines state-of-the-art technologies and research that strive to bridge these gaps. The physiol. of sweat, materials, biosensing mechanisms and advances, and approaches for sweat induction and sampling are introduced. Addnl., design considerations for the system-level development of wearable sweat sensing devices, spanning from strategies for prolonged sweat extn. to efficient powering of wearables, are discussed. Furthermore, the applications, data analytics, commercialization efforts, challenges, and prospects of wearable sweat sensors for precision medicine are discussed.
- 331Yang, Y.; Gao, W. Wearable and flexible electronics for continuous molecular monitoring. Chem. Soc. Rev. 2019, 48, 1465– 1491, DOI: 10.1039/C7CS00730BGoogle Scholar331Wearable and flexible electronics for continuous molecular monitoringYang, Yiran; Gao, WeiChemical Society Reviews (2019), 48 (6), 1465-1491CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)A review. Wearable biosensors have received tremendous attention over the past decade owing to their great potential in predictive analytics and treatment toward personalized medicine. Flexible electronics could serve as an ideal platform for personalized wearable devices because of their unique properties such as light wt., low cost, high flexibility and great conformability. Unlike most reported flexible sensors that mainly track phys. activities and vital signs, the new generation of wearable and flexible chem. sensors enables real-time, continuous and fast detection of accessible biomarkers from the human body, and allows for the collection of large-scale information about the individuals dynamic health status at the mol. level. In this article, we review and highlight recent advances in wearable and flexible sensors toward continuous and non-invasive mol. anal. in sweat, tears, saliva, interstitial fluid, blood, wound exudate as well as exhaled breath. The flexible platforms, sensing mechanisms, and device and system configurations employed for continuous monitoring are summarized. We also discuss the key challenges and opportunities of the wearable and flexible chem. sensors that lie ahead.
- 332Chung, M.; Fortunato, G.; Radacsi, N. Wearable flexible sweat sensors for healthcare monitoring: a review. J. R Soc. Interface 2019, 16, 20190217– 20190217, DOI: 10.1098/rsif.2019.0217Google Scholar332Wearable flexible sweat sensors for healthcare monitoring: a reviewChung, Michael; Fortunato, Giuseppino; Radacsi, NorbertJournal of the Royal Society, Interface (2019), 16 (159), 20190217CODEN: JRSICU; ISSN:1742-5662. (Royal Society)A review. The state-of-the-art in wearable flexible sensors (WFSs) for sweat analyte detection was investigated. Recent advances show the development of integrated, mech. flexible and multiplexed sensor systems with on-site circuitry for signal processing and wireless data transmission. When compared with single-analyte sensors, such devices provide an opportunity to more accurately analyze analytes that are dependent on other parameters (such as sweat rate and pH) by improving calibration from in situ real-time anal., while maintaining a lightwt. and wearable design. Important health conditions can be monitored and on-demand regulating drugs can be delivered using integrated wearable systems but require correlation verification between sweat and blood measurements using in vivo validation tests before any clin. application can be considered. Improvements are necessary for device sensitivity, accuracy and repeatability to provide more reliable and personalized continuous measurements. With rapid recent development, it can be concluded that non-invasive WFSs for sweat anal. have only skimmed the surface of their health monitoring potential and further significant advancement is sure to be made in the medical field.
- 333Suzuki, S.; Yoshimura, M. Chemical Stability of Graphene Coated Silver Substrates for Surface-Enhanced Raman Scattering. Sci. Rep. 2017, 7, 14851, DOI: 10.1038/s41598-017-14782-2Google Scholar333Chemical Stability of Graphene Coated Silver Substrates for Surface-Enhanced Raman ScatteringSuzuki Seiya; Yoshimura MasamichiScientific reports (2017), 7 (1), 14851 ISSN:.Surface enhanced Raman spectroscopy (SERS) is a novel method to sense molecular and lattice vibrations at a high sensitivity. Although nanostructured silver surface provides intense SERS signals, the silver surface is unstable under acidic environment and heated environment. Graphene, a single atomic carbon layer, has a prominent stability for chemical agents, and its honeycomb lattice completely prevents the penetration of small molecules. Here, we fabricated a SERS substrate by combining nanostructured silver surface and single-crystal monolayer graphene (G-SERS), and focused on its chemical stability. The G-SERS substrate showed SERS even in concentrated hydrochloric acid (35-37%) and heated air up to 400 °C, which is hardly obtainable by normal silver SERS substrates. The chemically stable G-SERS substrate posesses a practical and feasible application, and its high chemical stability provides a new type of SERS technique such as molecular detections at high temperatures or in extreme acidic conditions.
- 334Yang, Y.; Liu, J.; Fu, Z.-W.; Qin, D. Galvanic Replacement-Free Deposition of Au on Ag for Core–Shell Nanocubes with Enhanced Chemical Stability and SERS Activity. J. Am. Chem. Soc. 2014, 136, 8153– 8156, DOI: 10.1021/ja502472xGoogle Scholar334Galvanic Replacement-Free Deposition of Au on Ag for Core-Shell Nanocubes with Enhanced Chemical Stability and SERS ActivityYang, Yin; Liu, Jingyue; Fu, Zheng-Wen; Qin, DongJournal of the American Chemical Society (2014), 136 (23), 8153-8156CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)The authors report a robust synthesis of Ag@Au core-shell nanocubes by directly depositing Au atoms on the surfaces of Ag nanocubes as conformal, ultrathin shells. The success relies on the introduction of a strong reducing agent to compete with and thereby block the galvanic replacement between Ag and HAuCl4. An ultrathin Au shell of 0.6 nm thick was able to protect the Ag in the core in an oxidative environment. Significantly, the core-shell nanocubes exhibited surface plasmonic properties essentially identical to those of the original Ag nanocubes, while the SERS activity showed a 5.4-fold further enhancement owing to an improvement in chem. enhancement. The combination of excellent SERS activity and chem. stability may enable a variety of new applications.
- 335Xiao, J.; Wang, J.; Luo, Y.; Xu, T.; Zhang, X. Wearable Plasmonic Sweat Biosensor for Acetaminophen Drug Monitoring. ACS Sens 2023, 8, 1766– 1773, DOI: 10.1021/acssensors.3c00063Google Scholar335Wearable Plasmonic Sweat Biosensor for Acetaminophen Drug MonitoringXiao, Jingyu; Wang, Jing; Luo, Yong; Xu, Tailin; Zhang, XuejiACS Sensors (2023), 8 (4), 1766-1773CODEN: ASCEFJ; ISSN:2379-3694. (American Chemical Society)Monitoring the acetaminophen dosage is important to prevent the occurrence of adverse reactions such as liver failure and kidney damage. Traditional approaches to monitoring acetaminophen dosage mainly rely on invasive blood collection. Herein, we developed a noninvasive microfluidic-based wearable plasmonic sensor to achieve simultaneous sweat sampling and acetaminophen drug monitoring for vital signs. The fabricated sensor employs an Au nanosphere cone array as the key sensing component, which poses a substrate with surface-enhanced Raman scattering (SERS) activity to noninvasively and sensitively detect the fingerprint of acetaminophen mols. based on its unique SERS spectrum. The developed sensor enabled the sensitive detection and quantification of acetaminophen at concns. as low as 0.13μM. We further evaluated the sweat sensor integrated with a Raman spectrometer for monitoring acetaminophen in drug-administered subjects. These results indicated that the sweat sensor could measure acetaminophen levels and reflect drug metab. The sweat sensors have revolutionized wearable sensing technol. by adopting label-free and sensitive mol. tracking methods for noninvasive and point-of-care drug monitoring and management.
- 336Mogera, U.; Guo, H.; Namkoong, M.; Rahman, M. S.; Nguyen, T.; Tian, L. Wearable plasmonic paper-based microfluidics for continuous sweat analysis. Sci. Adv. 2022, 8, eabn1736, DOI: 10.1126/sciadv.abn1736Google ScholarThere is no corresponding record for this reference.
- 337Wang, Y.; Zhao, C.; Wang, J.; Luo, X.; Xie, L.; Zhan, S.; Kim, J.; Wang, X.; Liu, X.; Ying, Y. Wearable plasmonic-metasurface sensor for noninvasive and universal molecular fingerprint detection on biointerfaces. Science Advances 2021, 7, eabe4553, DOI: 10.1126/sciadv.abe4553Google ScholarThere is no corresponding record for this reference.
- 338Koh, E. H.; Lee, W. C.; Choi, Y. J.; Moon, J. I.; Jang, J.; Park, S. G.; Choo, J.; Kim, D. H.; Jung, H. S. A Wearable Surface-Enhanced Raman Scattering Sensor for Label-Free Molecular Detection. ACS Appl. Mater. Interfaces 2021, 13, 3024– 3032, DOI: 10.1021/acsami.0c18892Google Scholar338A wearable surface-enhanced raman scattering sensor for label-free molecular detectionKoh, Eun Hye; Lee, Won-Chul; Choi, Yeong-Jin; Moon, Joung-Il; Jang, Jinah; Park, Sung-Gyu; Choo, Jaebum; Kim, Dong-Ho; Jung, Ho SangACS Applied Materials & Interfaces (2021), 13 (2), 3024-3032CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)A wearable surface-enhanced Raman scattering (SERS) sensor has been developed as a patch type to utilize as a mol. sweat sensor. Here, the SERS patch sensor is designed to comprise a sweat-absorbing layer, which is an interface to the human skin, an SERS active layer, and a dermal protecting layer that prevents damage and contaminations. A silk fibroin protein film (SFF) is a basement layer that absorbs aq. solns. and filtrates mols. larger than the nanopores created in the β-sheet matrix of the SFF. On the SFF layer, a plasmonic silver nanowire (AgNW) layer is formed to enhance the Raman signal of the mols. that penetrated through the SERS patch in a label-free method. A transparent dermal protecting layer (DP) allows laser penetration to the AgNW layer enabling Raman measurement through the SERS patch without its detachment from the surface. The mol. detection capability and time-dependent absorption properties of the SERS patch are investigated, and then, the feasibility of its use as a wearable drug detection sweat sensor is demonstrated using 2-fluoro-methamphetamine (2-FMA) on the human cadaver skin. It is believed that the developed SERS patch can be utilized as various flexible and wearable biosensors for healthcare monitoring.
- 339Chung, M.; Skinner, W. H.; Robert, C.; Campbell, C. J.; Rossi, R. M.; Koutsos, V.; Radacsi, N. Fabrication of a Wearable Flexible Sweat pH Sensor Based on SERS-Active Au/TPU Electrospun Nanofibers. ACS Appl. Mater. Interfaces 2021, 13, 51504– 51518, DOI: 10.1021/acsami.1c15238Google Scholar339Fabrication of a Wearable Flexible Sweat pH Sensor Based on SERS-Active Au/TPU Electrospun NanofibersChung, Michael; Skinner, William H.; Robert, Colin; Campbell, Colin J.; Rossi, Rene M.; Koutsos, Vasileios; Radacsi, NorbertACS Applied Materials & Interfaces (2021), 13 (43), 51504-51518CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Development of wearable sensing platforms is essential for the advancement of continuous health monitoring and point-of-care testing. Eccrine sweat pH is an analyte that can be noninvasively measured and used to diagnose and aid in monitoring a wide range of physiol. conditions. Surface-enhanced Raman scattering (SERS) offers a rapid, optical technique for fingerprinting of biomarkers present in sweat. In this paper, a mech. flexible, nanofibrous, SERS-active substrate was fabricated by a combination of electrospinning of thermoplastic polyurethane (TPU) and Au sputter coating. This substrate was then investigated for suitability toward wearable sweat pH sensing after functionalization with two commonly used pH-responsive mols., 4-mercaptobenzoic acid (4-MBA), and 4-mercaptopyridine (4-MPy). The developed SERS pH sensor was found to have good resoln. (0.14 pH units for 4-MBA; 0.51 pH units for 4-MPy), with only 1μL of sweat required for a measurement, and displayed no statistically significant difference in performance after 35 days (p = 0.361). Addnl., the Au/TPU nanofibrous SERS pH sensors showed fast sweat-absorbing ability as well as good repeatability and reversibility. The proposed methodol. offers a facile route for the fabrication of SERS substrates which could also be used to measure a wide range of health biomarkers beyond sweat pH.
- 340Liu, L.; Martinez Pancorbo, P.; Xiao, T. H.; Noguchi, S.; Marumi, M.; Segawa, H.; Karhadkar, S.; Gala de Pablo, J.; Hiramatsu, K.; Kitahama, Y.; Itoh, T.; Qu, J.; Takei, K.; Goda, K. Highly Scalable, Wearable Surface-Enhanced Raman Spectroscopy. Advanced Optical Materials 2022, 10, 2200054, DOI: 10.1002/adom.202200054Google Scholar340Highly Scalable, Wearable Surface-Enhanced Raman SpectroscopyLiu, Limei; Martinez Pancorbo, Pablo; Xiao, Ting-Hui; Noguchi, Saya; Marumi, Machiko; Segawa, Hiroki; Karhadkar, Siddhant; Gala de Pablo, Julia; Hiramatsu, Kotaro; Kitahama, Yasutaka; Itoh, Tamitake; Qu, Junle; Takei, Kuniharu; Goda, KeisukeAdvanced Optical Materials (2022), 10 (17), 2200054CODEN: AOMDAX; ISSN:2195-1071. (Wiley-VCH Verlag GmbH & Co. KGaA)The last two decades have witnessed a dramatic growth of wearable sensor technol., mainly represented by flexible, stretchable, on-skin electronic sensors that provide rich information of the wearer's health conditions and surroundings. A recent breakthrough in the field is the development of wearable chem. sensors based on surface-enhanced Raman spectroscopy (SERS) that can detect mol. fingerprints universally, sensitively, and noninvasively. However, while their sensing properties are excellent, these sensors are not scalable for widespread use beyond small-scale human health monitoring due to their cumbersome fabrication process and limited multifunctional sensing capabilities. Here, a highly scalable, wearable SERS sensor is demonstrated based on an easy-to-fabricate, low-cost, ultrathin, flexible, stretchable, adhesive, and biointegratable gold nanomesh. It can be fabricated in any shape and worn on virtually any surface for label-free, large-scale, in situ sensing of diverse analytes from low to high concns. (10-106 x 10-9M). To show the practical utility of the wearable SERS sensor, the sensor is tested for the detection of sweat biomarkers, drugs of abuse, and microplastics. This wearable SERS sensor represents a significant step toward the generalizability and practicality of wearable sensing technol.
- 341He, X.; Fan, C.; Luo, Y.; Xu, T.; Zhang, X. Flexible microfluidic nanoplasmonic sensors for refreshable and portable recognition of sweat biochemical fingerprint. npj Flexible Electronics 2022, 6, 60, DOI: 10.1038/s41528-022-00192-6Google Scholar341Flexible microfluidic nanoplasmonic sensors for refreshable and portable recognition of sweat biochemical fingerprintHe, Xuecheng; Fan, Chuan; Luo, Yong; Xu, Tailin; Zhang, Xuejinpj Flexible Electronics (2022), 6 (1), 60CODEN: NFEPB8; ISSN:2397-4621. (Nature Portfolio)Wearable sweat sensors with various sensing systems can provide noninvasive medical diagnostics and healthcare monitoring. Here, we demonstrate a wearable microfluidic nanoplasmonic sensor capable of refreshable and portable recognition fingerprint information of targeted biomarkers including urea, lactate, and pH in sweat. A miniature, thin plasmonic metasurface with homogeneous mushroom-shaped hot spots and high surface-enhanced Raman scattering (SERS) activity is designed and integrated into a microfluidics platform. Compared to conventional wearable SERS platforms with the risk of mixed effect between new and old sweat, the microfluidic SERS system allows sweat administration in a controllable and high temporal-resoln. fashion, providing refreshable SERS anal. We use a portable and customized Raman analyzer with a friendly human-machine interface for portable recognition of the spectroscopic signatures of sweat biomarkers. This study integrates epidermal microfluidics with portable SERS mol. recognition, presenting a controllable, handy, and dynamical biofluid sensing system for personalized medicine.
- 342Zhu, K.; Yang, K.; Zhang, Y.; Yang, Z.; Qian, Z.; Li, N.; Li, L.; Jiang, G.; Wang, T.; Zong, S.; Wu, L.; Wang, Z.; Cui, Y. Wearable SERS Sensor Based on Omnidirectional Plasmonic Nanovoids Array with Ultra-High Sensitivity and Stability. Small 2022, 18, e2201508, DOI: 10.1002/smll.202201508Google Scholar342Wearable SERS Sensor Based on Omnidirectional Plasmonic Nanovoids Array with Ultra-High Sensitivity and StabilityZhu, Kai; Yang, Kuo; Zhang, Yizhi; Yang, Zhaoyan; Qian, Ziting; Li, Na; Li, Lang; Jiang, Guohua; Wang, Tingyu; Zong, Shenfei; Wu, Lei; Wang, Zhuyuan; Cui, YipingSmall (2022), 18 (32), 2201508CODEN: SMALBC; ISSN:1613-6810. (Wiley-VCH Verlag GmbH & Co. KGaA)Surface-enhanced Raman spectroscopy (SERS) is a promising technol. for wearable sensors due to its fingerprint spectrum and high detection sensitivity. However, since SERS-activity is sensitive to both the distribution of "hotspots" and excitation angle, it is profoundly challenging to develop a wearable SERS sensor with high stability under various deformations during movements. Herein, inspired by omnidirectional light-harvesting of the compd. eye of Xenos Peckii, a wearable SERS sensor is developed using omnidirectional plasmonic nanovoids array (OPNA), which is prepd. by assembling a monolayer of metal nanoparticles into the artificial plasmonic compd.-eye (APC). Specifically, APC is an interconnected frame contg. omnidirectional "pockets" and acts as an "armour", not only rendering a broadband and omnidirectional enhancement of "hotspots" in the delicate nanoparticles array, but also maintaining an integrity of the "hotspots" against external mech. deformations. Furthermore, an asymmetry super-hydrophilic pattern is fabricated on the surface of OPNA, endowing the hydrophobic OPNA with the ability to spontaneously ext. and conc. the analytes from sweat. Such an armored SERS sensor can enable the wearable and in situ anal. with high sensitivity and stability, exhibiting great potential in point-of-care anal.
- 343Lee, C. H.; Hankus, M. E.; Tian, L.; Pellegrino, P. M.; Singamaneni, S. Highly Sensitive Surface Enhanced Raman Scattering Substrates Based on Filter Paper Loaded with Plasmonic Nanostructures. Anal. Chem. 2011, 83, 8953– 8958, DOI: 10.1021/ac2016882Google Scholar343Highly Sensitive Surface Enhanced Raman Scattering Substrates Based on Filter Paper Loaded with Plasmonic NanostructuresLee, Chang H.; Hankus, Mikella E.; Tian, Limei; Pellegrino, Paul M.; Singamaneni, SrikanthAnalytical Chemistry (Washington, DC, United States) (2011), 83 (23), 8953-8958CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)The authors report a novel surface enhanced Raman scattering (SERS) substrate platform based on a common filter paper adsorbed with plasmonic nanostructures that overcomes many of the challenges assocd. with existing SERS substrates. The paper-based design results in a substrate that combines all of the advantages of conventional rigid and planar SERS substrates in a dynamic flexible scaffolding format. The fabrication, phys. characterization, and SERS activity of the authors' novel substrates using nonresonant analytes are discussed. The SERS substrate is highly sensitive, robust, and amiable to several different environments and target analytes. It is also cost-efficient and demonstrates high sample collection efficiency and does not require complex fabrication methodologies. The paper substrate has high sensitivity (0.5 nM trans-1,2-bis(4-pyridyl)ethene (BPE)) and excellent reproducibility (∼15% relative std. deviation ). The paper substrates demonstrated here establish a novel platform for integrating SERS with already existing anal. techniques such as chromatog. and microfluidics, imparting chem. specificity to these techniques.
- 344Lee, C. H.; Tian, L.; Singamaneni, S. Paper-Based SERS Swab for Rapid Trace Detection on Real-World Surfaces. ACS Appl. Mater. Interfaces 2010, 2, 3429– 3435, DOI: 10.1021/am1009875Google Scholar344Paper-based SERS swab for rapid trace detection on real-world surfacesLee, Chang H.; Tian, Limei; Singamaneni, SrikanthACS Applied Materials & Interfaces (2010), 2 (12), 3429-3435CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)One of the important but often overlooked considerations in the design of surface-enhanced Raman scattering (SERS) substrates for trace detection is the efficiency of sample collection. Conventional designs based on rigid substrates such as silicon, alumina, and glass resist conformal contact with the surface under study, making the sample collection inefficient. The authors demonstrate a novel SERS substrate based on common filter paper adsorbed with gold nanorods, which allows conformal contact with real-world surfaces, thus dramatically enhancing the sample collection efficiency compared to conventional rigid substrates. The authors demonstrate the detection of trace amts. of analyte (140 pg spread over 4 cm2) by simply swabbing the surface under study with the novel SERS substrate. The hierarchical fibrous structure of paper serves as a 3-dimensional vasculature for easy uptake and transport of the analytes to the electromagnetic hot spots. Simple yet highly efficient and cost-effective SERS substrate demonstrated here brings SERS-based trace detection closer to real-world applications.
- 345Liu, X.; Li, T.; Lee, T. C.; Sun, Y.; Liu, Y.; Shang, L.; Han, Y.; Deng, W.; Yuan, Z.; Dang, A. Wearable Plasmonic Sensors Engineered via Active-Site Maximization of TiVC MXene for Universal Physiological Monitoring at the Molecular Level. ACS Sens 2024, 9, 483– 493, DOI: 10.1021/acssensors.3c02285Google Scholar345Wearable Plasmonic Sensors Engineered via Active-Site Maximization of TiVC MXene for Universal Physiological Monitoring at the Molecular LevelLiu, Xin; Li, Tiehu; Lee, Tung-Chun; Sun, Yiting; Liu, Yuhui; Shang, Li; Han, Yanying; Deng, Weibin; Yuan, Zeqi; Dang, AleiACS Sensors (2024), 9 (1), 483-493CODEN: ASCEFJ; ISSN:2379-3694. (American Chemical Society)Two-dimensional transition metal carbon/nitrides (MXenes) are promising candidates to revolutionize next-generation wearable sensors as high-performance surface-enhanced Raman scattering (SERS) substrates. However, low sensitivity of pure MXene nanosheets and weak binding force or uncontrolled in situ growth of plasmonic nanoparticles on hybrid MXene composites limit their progress toward universal and reliable sensors. Herein, we designed and manufd. a highly sensitive, structurally stable wearable SERS sensor by in situ fabrication of plasmonic nanostructures on the flexible TiVC membranes via the maximization of chem. reducing sites using alk. treatment. DFT calcns. and exptl. characterization demonstrated that the hydroxyl functional groups on the surface of MXenes can facilitate the redn. of metal precursors and the nucleation of gold nanoparticles (AuNPs) and can be covalently attached to AuNPs. Thus, the fabricated flexible TiVC-OH-Au sensor satisfied the rigorous mech. requirements for wearable sensors. In addn., combining the electromagnetic (EM) enhancement from dense AuNPs formed by the activation of nucleation sites and charge transfer (CT) between target mol. and substrate induced by the abundant DOS near the Fermi level of TiVC, the fabricated sensor exhibits ultrasensitivity, long-term stability, good signal repeatability, and excellent mech. durability. Moreover, the proof-of-concept application of the wearable SERS sensor in sweat sensing was demonstrated to monitor the content of nicotine, methotrexate, nikethamide, and 6-acetylmorphine in sweat at the mol. level, which was an important step toward the universality and practicality of the wearable sensing technol.
- 346Nergiz, S. Z.; Gandra, N.; Farrell, M. E.; Tian, L. M.; Pellegrino, P. M.; Singamaneni, S. Biomimetic SERS substrate: peptide recognition elements for highly selective chemical detection in chemically complex media. J. Mater. Chem. A 2013, 1, 6543– 6549, DOI: 10.1039/c3ta00138eGoogle Scholar346Biomimetic SERS substrate: peptide recognition elements for highly selective chemical detection in chemically complex mediaNergiz, Saide Z.; Gandra, Naveen; Farrell, Mikella E.; Tian, Limei; Pellegrino, Paul M.; Singamaneni, SrikanthJournal of Materials Chemistry A: Materials for Energy and Sustainability (2013), 1 (22), 6543-6549CODEN: JMCAET; ISSN:2050-7496. (Royal Society of Chemistry)Surface enhanced Raman scattering (SERS) is rapidly emerging as a sensitive transduction platform for the trace detection of chem. and biol. analytes. A crit. challenge that needs to be addressed to propel this technique into real world applications is the poor chem. selectivity of the existing SERS substrates. The authors demonstrate a novel biomimetic approach to enhance the selectivity of plasmonic nanostructures to target chem. analytes. In particular, material-binding peptides, identified through phage-display, serve as recognition elements for selective capture of target chem. species from a complex chem. mixt. As a proof of concept, a nitroarom. explosive mol., trinitrotoluene (TNT), can be detected down to 100 pM concn. even in a complex org. chem. mixt. This ultrasensitive and selective detection is enabled by TNT-binding peptides appended to Au nanorods, which serve as selective SERS media. To the best of the authors' knowledge, this is the 1st demonstration of a biomimetic SERS substrate facilitating selective and sensitive detection of a target chem. analyte in the presence of numerous unknown interfering species.
- 347Tian, L.; Jiang, Q.; Liu, K.-K.; Luan, J.; Naik, R. R.; Singamaneni, S. Bacterial Nanocellulose-Based Flexible Surface Enhanced Raman Scattering Substrate. Advanced Materials Interfaces 2016, 3, 1600214, DOI: 10.1002/admi.201670073Google ScholarThere is no corresponding record for this reference.
- 348Tian, L.; Luan, J.; Liu, K.-K.; Jiang, Q.; Tadepalli, S.; Gupta, M. K.; Naik, R. R.; Singamaneni, S. Plasmonic Biofoam: A Versatile Optically Active Material. Nano Lett. 2016, 16, 609– 616, DOI: 10.1021/acs.nanolett.5b04320Google Scholar348Plasmonic Biofoam: A Versatile Optically Active MaterialTian, Limei; Luan, Jingyi; Liu, Keng-Ku; Jiang, Qisheng; Tadepalli, Sirimuvva; Gupta, Maneesh K.; Naik, Rajesh R.; Singamaneni, SrikanthNano Letters (2016), 16 (1), 609-616CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)The authors demonstrate a simple method to create plasmonically active three-dimensional biofoams by integrating plasmonic nanostructures with highly porous biomaterial aerogels. Plasmonic biofoam is a versatile optically active platform that can be harnessed for numerous applications including (i) ultrasensitive chem. detection using surface-enhanced Raman scattering; (ii) highly efficient energy harvesting and steam generation through plasmonic photothermal heating; and (iii) optical control of enzymic activity by triggered release of biomols. encapsulated within the aerogel. 3D plasmonic biofoam exhibits significantly higher sensing, photothermal, and loading efficiency compared to conventional 2D counterparts.
- 349Tian, L.; Morrissey, J. J.; Kattumenu, R.; Gandra, N.; Kharasch, E. D.; Singamaneni, S. Bioplasmonic Paper as a Platform for Detection of Kidney Cancer Biomarkers. Anal. Chem. 2012, 84, 9928– 9934, DOI: 10.1021/ac302332gGoogle Scholar349Bioplasmonic Paper as a Platform for Detection of Kidney Cancer BiomarkersTian, Limei; Morrissey, Jeremiah J.; Kattumenu, Ramesh; Gandra, Naveen; Kharasch, Evan D.; Singamaneni, SrikanthAnalytical Chemistry (Washington, DC, United States) (2012), 84 (22), 9928-9934CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)We demonstrate that a common lab. filter paper uniformly adsorbed with biofunctionalized plasmonic nanostructures can serve as a highly sensitive transduction platform for rapid detection of trace bioanalytes in physiol. fluids. In particular, we demonstrate that bioplasmonic paper enables rapid urinalysis for the detection of kidney cancer biomarkers in artificial urine down to a concn. of 10 ng/mL. Compared to conventional rigid substrates, bioplasmonic paper offers numerous advantages such as high sp. surface area (resulting in large dynamic range), excellent wicking properties (naturally microfluidic), mech. flexibility, compatibility with conventional printing approaches (enabling multiplexed detection and multimarker biochips), and significant cost redn.
- 350Tian, L.; Tadepalli, S.; Hyun Park, S.; Liu, K.-K.; Morrissey, J. J.; Kharasch, E. D.; Naik, R. R.; Singamaneni, S. Bioplasmonic calligraphy for multiplexed label-free biodetection. Biosens. Bioelectron. 2014, 59, 208– 215, DOI: 10.1016/j.bios.2014.03.043Google Scholar350Bioplasmonic calligraphy for multiplexed label-free biodetectionTian, Limei; Tadepalli, Sirimuvva; Park, Sang Hyun; Liu, Keng-Ku; Morrissey, Jeremiah J.; Kharasch, Evan D.; Naik, Rajesh R.; Singamaneni, SrikanthBiosensors & Bioelectronics (2014), 59 (), 208-215CODEN: BBIOE4; ISSN:0956-5663. (Elsevier B.V.)Printable multi-marker biochips that enable simultaneous quant. detection of multiple target biomarkers in point-of-care and resource-limited settings are a holy grail in the field of biodiagnostics. However, preserving the functionality of biomols., which are routinely employed as recognition elements, during conventional printing approaches remains challenging. In this article, we introduce a simple yet powerful approach, namely plasmonic calligraphy, for realizing multiplexed label-free bioassays. Plasmonic calligraphy involves a regular ballpoint pen filled with biofunctionalized gold nanorods as plasmonic ink for creating isolated test domains on paper substrates. Biofriendly plasmonic calligraphy approach serves as a facile method to miniaturize the test domain size to few mm2, which significantly improves the sensitivity of the plasmonic biosensor compared to bioplasmonic paper fabricated using immersion approach. Furthermore, plasmonic calligraphy also serves as a simple and efficient means to isolate multiple test domains on a single test strip, which facilitates multiplexed biodetection and multi-marker biochips. Plasmonic calligraphy, which can be potentially automated by implementing with a robotic arm, serves as an alternate path forward to overcome the limitations of conventional ink-jet printing.
- 351Tian, L. M.; Tadepalli, S.; Farrell, M. E.; Liu, K. K.; Gandra, N.; Pellegrino, P. M.; Singamaneni, S. Multiplexed charge-selective surface enhanced Raman scattering based on plasmonic calligraphy. J. Mater. Chem. C 2014, 2, 5438– 5446, DOI: 10.1039/c4tc00768aGoogle Scholar351Multiplexed charge-selective surface enhanced Raman scattering based on plasmonic calligraphyTian, Limei; Tadepalli, Sirimuvva; Farrell, Mikella E.; Liu, Keng-Ku; Gandra, Naveen; Pellegrino, Paul M.; Singamaneni, SrikanthJournal of Materials Chemistry C: Materials for Optical and Electronic Devices (2014), 2 (27), 5438-5446CODEN: JMCCCX; ISSN:2050-7534. (Royal Society of Chemistry)Multiplexed surface enhanced Raman scattering (SERS) substrates, which enable chem. selective detection of two or more target analytes from a complex chem. mixt., are highly attractive for chem. detection in real-world settings. We introduce a new approach called plasmonic calligraphy that involves the formation of chem. selective test domains on paper substrates using functionalized plasmonic nanostructures as ink in a regular ballpoint pen. We demonstrate selective detection of pos. and neg. charged analytes (rhodamine 6G and methyl orange) from complex chem. mixts. using polyelectrolyte-coated gold nanorods as SERS medium. The approach demonstrated here obviates the need for complex patterning techniques such as photolithog. to create isolated test domains on paper substrates for multiplexed chem. detection. Plasmonic calligraphy can be easily extended to other shape-controlled nanostructures with different surface functionalities and potentially automated by implementation with a robotic arm.
- 352Yin, Z.; Guo, H.; Li, Y.; Chiu, J.; Tian, L. Ultrastable Plasmonic Bioink for Printable Point-Of-Care Biosensors. ACS Appl. Mater. Interfaces 2020, 12, 35977– 35985, DOI: 10.1021/acsami.0c11799Google Scholar352Ultrastable Plasmonic Bioink for Printable Point-Of-Care BiosensorsYin, Ze; Guo, Heng; Li, Yixuan; Chiu, Joshua; Tian, LimeiACS Applied Materials & Interfaces (2020), 12 (32), 35977-35985CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Point-of-care biosensors are critically important for early disease diagnosis and timely clin. intervention in resource-limited settings. The real-world application of these biosensors requires the use of stable biol. reagents and cost-effective fabrication approaches. To meet these stringent requirements, the authors introduce a generic encapsulation strategy to realize ultrastable plasmonic bioink by encapsulating antibodies with an organosiloxane polymer through in situ polymn. Plasmonic nanostructures serve as sensitive nanotransducers, allowing for label-free biochem. detection. The plasmonic bioink with encapsulated antibodies exhibits excellent thermal, biol., and colloidal stabilities making it compatible with printing process. As a proof-of-concept, the authors demonstrate the printability of the ultrastable plasmonic bioinks on different types of substrates with direct writing techniques. The organosiloxane polymer preserves the biorecognition capabilities of the biosensors under harsh conditions, including elevated temp., exposure to chem./biol. denaturants, and ultrasonic agitation. Plasmonic biochips fabricated with the ultrastable ink exhibit superior stability compared to the biochips with unencapsulated antibodies.
- 353Kant, K.; Beeram, R.; Cao, Y.; dos Santos, P. S. S.; González-Cabaleiro, L.; García-Lojo, D.; Guo, H.; Joung, Y.; Kothadiya, S.; Lafuente, M.; Leong, Y. X.; Liu, Y.; Liu, Y.; Moram, S. S. B.; Mahasivam, S.; Maniappan, S.; Quesada-González, D.; Raj, D.; Weerathunge, P.; Xia, X.; Yu, Q.; Abalde-Cela, S.; Alvarez-Puebla, R. A.; Bardhan, R.; Bansal, V.; Choo, J.; Coelho, L. C. C.; de Almeida, J. M. M. M.; Gómez-Graña, S.; Grzelczak, M.; Herves, P.; Kumar, J.; Lohmueller, T.; Merkoçi, A.; Montaño-Priede, J. L.; Ling, X. Y.; Mallada, R.; Pérez-Juste, J.; Pina, M. P.; Singamaneni, S.; Soma, V. R.; Sun, M.; Tian, L.; Wang, J.; Polavarapu, L.; Santos, I. P. Plasmonic nanoparticle sensors: current progress, challenges, and future prospects. Nanoscale Horizons 2024, 9, 2085, DOI: 10.1039/D4NH00226AGoogle ScholarThere is no corresponding record for this reference.
- 354Heikenfeld, J.; Jajack, A.; Rogers, J.; Gutruf, P.; Tian, L.; Pan, T.; Li, R.; Khine, M.; Kim, J.; Wang, J.; Kim, J. Wearable sensors: modalities, challenges, and prospects. Lab Chip 2018, 18, 217– 248, DOI: 10.1039/C7LC00914CGoogle Scholar354Wearable sensors: modalities, challenges, and prospectsHeikenfeld, J.; Jajack, A.; Rogers, J.; Gutruf, P.; Tian, L.; Pan, T.; Li, R.; Khine, M.; Kim, J.; Wang, J.; Kim, J.Lab on a Chip (2018), 18 (2), 217-248CODEN: LCAHAM; ISSN:1473-0189. (Royal Society of Chemistry)Wearable sensors have recently seen a large increase in both research and commercialization. However, success in wearable sensors has been a mix of both progress and setbacks. Most of com. progress has been in smart adaptation of existing mech., elec. and optical methods of measuring the body. This adaptation has involved innovations in how to miniaturize sensing technologies, how to make them conformal and flexible, and in the development of companion software that increases the value of the measured data. However, chem. sensing modalities have experienced greater challenges in com. adoption, esp. for non-invasive chem. sensors. There have also been significant challenges in making significant fundamental improvements to existing mech., elec., and optical sensing modalities, esp. in improving their specificity of detection. Many of these challenges can be understood by appreciating the body's surface (skin) as more of an information barrier than as an information source. With a deeper understanding of the fundamental challenges faced for wearable sensors and of the state-of-the-art for wearable sensor technol., the roadmap becomes clearer for creating the next generation of innovations and breakthroughs.
- 355Tian, L.; Zimmerman, B.; Akhtar, A.; Yu, K. J.; Moore, M.; Wu, J.; Larsen, R. J.; Lee, J. W.; Li, J.; Liu, Y.; Metzger, B.; Qu, S.; Guo, X.; Mathewson, K. E.; Fan, J. A.; Cornman, J.; Fatina, M.; Xie, Z.; Ma, Y.; Zhang, J.; Zhang, Y.; Dolcos, F.; Fabiani, M.; Gratton, G.; Bretl, T.; Hargrove, L. J.; Braun, P. V.; Huang, Y.; Rogers, J. A. Large-area MRI-compatible epidermal electronic interfaces for prosthetic control and cognitive monitoring. Nature Biomedical Engineering 2019, 3, 194– 205, DOI: 10.1038/s41551-019-0347-xGoogle ScholarThere is no corresponding record for this reference.
- 356Chandra, S.; Li, J.; Afsharipour, B.; Cardona, A. F.; Suresh, N. L.; Tian, L.; Deng, Y.; Zhong, Y.; Xie, Z.; Shen, H.; Huang, Y.; Rogers, J. A.; Rymer, W. Z. Performance Evaluation of a Wearable Tattoo Electrode Suitable for High-Resolution Surface Electromyogram Recording. IEEE Transactions on Biomedical Engineering 2021, 68, 1389– 1398, DOI: 10.1109/TBME.2020.3032354Google ScholarThere is no corresponding record for this reference.
- 357Zhang, H.; Zhao, H.; Zhao, X.; Xu, C.; Franklin, D.; Vázquez-Guardado, A.; Bai, W.; Zhao, J.; Li, K.; Monti, G.; Lu, W.; Kobeissi, A.; Tian, L.; Ning, X.; Yu, X.; Mehta, S.; Chanda, D.; Huang, Y.; Xu, S.; Perez White, B. E.; Rogers, J. A. Biocompatible Light Guide-Assisted Wearable Devices for Enhanced UV Light Delivery in Deep Skin. Adv. Funct. Mater. 2021, 31, 2100576, DOI: 10.1002/adfm.202100576Google ScholarThere is no corresponding record for this reference.
- 358Namkoong, M.; Guo, H.; Rahman, M. S.; Wang, D.; Pfeil, C. J.; Hager, S.; Tian, L. Moldable and transferrable conductive nanocomposites for epidermal electronics. npj Flexible Electronics 2022, 6, 41, DOI: 10.1038/s41528-022-00170-yGoogle ScholarThere is no corresponding record for this reference.
- 359Deo, K. A.; Jaiswal, M. K.; Abasi, S.; Lokhande, G.; Bhunia, S.; Nguyen, T.-U.; Namkoong, M.; Darvesh, K.; Guiseppi-Elie, A.; Tian, L.; Gaharwar, A. K. Nanoengineered Ink for Designing 3D Printable Flexible Bioelectronics. ACS Nano 2022, 16, 8798– 8811, DOI: 10.1021/acsnano.1c09386Google Scholar359Nanoengineered Ink for Designing 3D Printable Flexible BioelectronicsDeo, Kaivalya A.; Jaiswal, Manish K.; Abasi, Sara; Lokhande, Giriraj; Bhunia, Sukanya; Nguyen, Thuy-Uyen; Namkoong, Myeong; Darvesh, Kamran; Guiseppi-Elie, Anthony; Tian, Limei; Gaharwar, Akhilesh K.ACS Nano (2022), 16 (6), 8798-8811CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Flexible electronics require elastomeric and conductive biointerfaces with native tissue-like mech. properties. The conventional approaches to engineer such a biointerface often utilize conductive nanomaterials in combination with polymeric hydrogels that are cross-linked using toxic photoinitiators. Moreover, these systems frequently demonstrate poor biocompatibility and face trade-offs between cond. and mech. stiffness under physiol. conditions. To address these challenges, we developed a class of shear-thinning hydrogels as biomaterial inks for 3D printing flexible bioelectronics. These hydrogels are engineered through a facile vacancy-driven gelation of MoS2 nanoassemblies with naturally derived polymer-thiolated gelatin. Due to shear-thinning properties, these nanoengineered hydrogels can be printed into complex shapes that can respond to mech. deformation. The chem. cross-linked nanoengineered hydrogels demonstrate a 20-fold rise in compressive moduli and can withstand up to 80% strain without permanent deformation, meeting human anatomical flexibility. The nanoengineered network exhibits high cond., compressive modulus, pseudocapacitance, and biocompatibility. The 3D-printed cross-linked structure demonstrates excellent strain sensitivity and can be used as wearable electronics to detect various motion dynamics. Overall, the results suggest that these nanoengineered hydrogels offer improved mech., electronic, and biol. characteristics for various emerging biomedical applications including 3D-printed flexible biosensors, actuators, optoelectronics, and therapeutic delivery devices.
- 360Roy, S.; Deo, K. A.; Lee, H. P.; Soukar, J.; Namkoong, M.; Tian, L.; Jaiswal, A.; Gaharwar, A. K. 3D Printed Electronic Skin for Strain, Pressure and Temperature Sensing. Adv. Funct. Mater. 2024, 34, 2313575, DOI: 10.1002/adfm.202470121Google ScholarThere is no corresponding record for this reference.
- 361Kim, H. S.; Kim, H. J.; Lee, J.; Lee, T.; Yun, J.; Lee, G.; Hong, Y. Hand-Held Raman Spectrometer-Based Dual Detection of Creatinine and Cortisol in Human Sweat Using Silver Nanoflakes. Anal. Chem. 2021, 93, 14996– 15004, DOI: 10.1021/acs.analchem.1c02496Google Scholar361Hand-held Raman spectrometer-based dual detection of creatinine and cortisol in human sweat using silver nanoflakesKim, Hyun Soo; Kim, Hyun Jung; Lee, Jaehun; Lee, Taeha; Yun, Jongsu; Lee, Gyudo; Hong, YoochanAnalytical Chemistry (Washington, DC, United States) (2021), 93 (45), 14996-15004CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)The conventional tissue biopsy method yields isolated snapshots of a narrow region. Therefore, it cannot facilitate comprehensive disease characterization and monitoring. Recently, the detection of tumor-derived components in body fluids-a practice known as liq. biopsy-has attracted increased attention from the biochem. research and clin. application viewpoints. In this vein, surface-enhanced Raman scattering (SERS) has been identified as one of the most powerful liq.-biopsy anal. techniques, owing to its high sensitivity and specificity. Moreover, it affords high-capacity spectral multiplexing for simultaneous target detection and a unique ability to obtain intrinsic biomol.-fingerprint spectra. This paper presents the fabrication of silver nanosnowflakes (SNSFs) using the polyol method and their subsequent dropping onto a hydrophobic filter paper. The SERS substrate, which comprises the SNSFs and hydrophobic filter paper, facilitates the simultaneous detection of creatinine and cortisol in human sweat using a hand-held Raman spectrometer. The proposed SERS system affords Raman spectrometry to be performed on small sample vols. (2μL) to identify the normal and at-risk creatinine and cortisol groups.
- 362Song, S.; Wang, L.; Li, J.; Fan, C.; Zhao, J. Aptamer-based biosensors. TrAC Trends in Analytical Chemistry 2008, 27, 108– 117, DOI: 10.1016/j.trac.2007.12.004Google Scholar362Aptamer-based biosensorsSong, Shiping; Wang, Lihua; Li, Jiang; Fan, Chunhai; Zhao, JianlongTrAC, Trends in Analytical Chemistry (2008), 27 (2), 108-117CODEN: TTAEDJ; ISSN:0165-9936. (Elsevier Ltd.)A review. Nucleic-acid aptamers have attracted intense interest and found wide applications in a range of areas. In this review, we summarize recent advances in the development of aptamer-based biosensors and bioassay methods, most of which have employed electrochem., optical and mass-sensitive anal. techniques. Aptamers exhibit many advantages as recognition elements in biosensing when compared to traditional antibodies. They are small in size, chem. stable and cost effective. More importantly, aptamers offer remarkable flexibility and convenience in the design of their structures, which has led to novel biosensors that have exhibited high sensitivity and selectivity. Recently, the combination of aptamers with novel nanomaterials has significantly improved the performance of aptamer-based sensors, which we also review in this article. In view of the unprecedented advantages brought by aptamers, we expect aptamer-based biosensors to find broad applications in biomedical diagnostics, environmental monitoring and homeland security.
- 363Abbas, A.; Tian, L.; Morrissey, J. J.; Kharasch, E. D.; Singamaneni, S. Hot Spot-Localized Artificial Antibodies for Label-Free Plasmonic Biosensing. Adv. Funct. Mater. 2013, 23, 1789– 1797, DOI: 10.1002/adfm.201202370Google Scholar363Hot Spot-Localized Artificial Antibodies for Label-Free Plasmonic BiosensingAbbas, Abdennour; Tian, Limei; Morrissey, Jeremiah J.; Kharasch, Evan D.; Singamaneni, SrikanthAdvanced Functional Materials (2013), 23 (14), 1789-1797CODEN: AFMDC6; ISSN:1616-301X. (Wiley-VCH Verlag GmbH & Co. KGaA)The development of biomol. imprinting over the last decade has raised promising perspectives in replacing natural antibodies with artificial antibodies. A significant no. of reports have been dedicated to imprinting of org. and inorg. nanostructures, but very few were performed on nanomaterials with a transduction function. Herein, a relatively fast and efficient plasmonic hot spot-localized surface imprinting of gold nanorods using reversible template immobilization and siloxane copolymn. is described. The technique enables a fine control of the imprinting process at the nanometer scale and provides a nanobiosensor with high selectivity and reusability. Proof of concept was established by the detection of neutrophil gelatinase-assocd. lipocalin (NGAL), a biomarker for acute kidney injury, using localized surface plasmon resonance spectroscopy. The work represents a valuable step towards plasmonic nanobiosensors with synthetic antibodies for label-free and cost-efficient diagnostic assays. It is expected that this novel class of surface imprinted plasmonic nanomaterials will open up new possibilities in advancing biomedical applications of plasmonic nanostructures.
- 364Tian, L. M.; Liu, K. K.; Morrissey, J. J.; Gandra, N.; Kharasch, E. D.; Singamaneni, S. Gold nanocages with built-in artificial antibodies for label-free plasmonic biosensing. J. Mater. Chem. B 2014, 2, 167– 170, DOI: 10.1039/C3TB21551BGoogle Scholar364Gold nanocages with built-in artificial antibodies for label-free plasmonic biosensingTian, Limei; Liu, Keng-Ku; Morrissey, Jeremiah J.; Gandra, Naveen; Kharasch, Evan D.; Singamaneni, SrikanthJournal of Materials Chemistry B: Materials for Biology and Medicine (2014), 2 (2), 167-170CODEN: JMCBDV; ISSN:2050-7518. (Royal Society of Chemistry)We demonstrate that gold nanocages (AuNCs) with built-in artificial antibodies enable the detection of kidney injury biomarker from synthetic urine down to a concn. of 25 ng ml-1. Molecularly imprinted AuNCs exhibit excellent selectivity against numerous interfering urinary proteins and remarkable stability over a wide range of pH and sp. gr.
- 365Garg, M.; Guo, H.; Maclam, E.; Zhanov, E.; Samudrala, S.; Pavlov, A.; Rahman, M. S.; Namkoong, M.; Moreno, J. P.; Tian, L. Molecularly Imprinted Wearable Sensor with Paper Microfluidics for Real-Time Sweat Biomarker Analysis. ACS Appl. Mater. Interfaces 2024, 16, 46113– 46122, DOI: 10.1021/acsami.4c10033Google ScholarThere is no corresponding record for this reference.
- 366Wang, W.; Chen, Y.; Xiao, C.; Xiao, S.; Wang, C.; Nie, Q.; Xu, P.; Chen, J.; You, R.; Zhang, G.; Lu, Y. Flexible SERS wearable sensor based on nanocomposite hydrogel for detection of metabolites and pH in sweat. Chemical Engineering Journal 2023, 474, 145953, DOI: 10.1016/j.cej.2023.145953Google Scholar366Flexible SERS wearable sensor based on nanocomposite hydrogel for detection of metabolites and pH in sweatWang, Wenxi; Chen, Yiming; Xiao, Chongxin; Xiao, Siying; Wang, Chuyi; Nie, Qingling; Xu, Peipei; Chen, Jingbo; You, Ruiyun; Zhang, Guifeng; Lu, YudongChemical Engineering Journal (Amsterdam, Netherlands) (2023), 474 (), 145953CODEN: CMEJAJ; ISSN:1385-8947. (Elsevier B.V.)Flexible wearable sensors can detect analytes continuously, in real time, and non-invasively, and their application in human health monitoring has received great attention. However, traditional sensors suffer from insufficient biocompatibility, wearing discomfort, and low detection sensitivity, so hydrogel is introduced as a sensor patch to improve the contact between skin and sensor, and combined with surface-enhanced Raman spectroscopy (SERS) technol. for rapid and sensitive anal. of biomarkers in sweat. Here, a flexible SERS wearable sensor based on a sulfonated cellulose nanocomposite hydrogel (S-CNF-Ag NPs/PAA) was developed. The hydrogel was prepd. by photo-crosslinking of sulfonated cellulose silver nanocomposites (S-CNF-Ag NPs) with acrylic acid (AA), which is a quick and easy prepn. process. The network structure of hydrogel can retain small mols. and adsorb sweat through hydrophilic groups, which diffuse sweat into the hydrogel and can effectively collect the analyses in sweat. The introduction of cellulose and silver nanoparticles not only provides excellent mech. and adhesive properties (toughness of 3790 kJ/m3, interfacial toughness of ∼116.23 J/m2), but also good antimicrobial properties and biocompatibility. The SERS technol. enabled the quant. anal. of metabolites in sweat (the detection limits for urea and uric acid were 63.1 μM and 3.98 μM, resp.) and real-time monitoring of pH. S-CNF-Ag NPs/PAA sensor maintained excellent sensitivity, stability and mech. properties during the detection process, effectively expanding the application of hydrogels in flexible SERS sensing and human health detection.
- 367Zong, C.; Cheng, R.; Chen, F.; Lin, P.; Zhang, M.; Chen, Z.; Li, C.; Yang, C.; Cheng, J.-X. Wide-Field Surface-Enhanced Coherent Anti-Stokes Raman Scattering Microscopy. ACS Photonics 2022, 9, 1042– 1049, DOI: 10.1021/acsphotonics.1c02015Google Scholar367Wide-Field Surface-Enhanced Coherent Anti-Stokes Raman Scattering MicroscopyZong, Cheng; Cheng, Ran; Chen, Fukai; Lin, Peng; Zhang, Meng; Chen, Zhicong; Li, Chuan; Yang, Chen; Cheng, Ji-XinACS Photonics (2022), 9 (3), 1042-1049CODEN: APCHD5; ISSN:2330-4022. (American Chemical Society)Surface-enhanced Raman scattering (SERS) spectroscopy has been used extensively to study biol., chem., and materials. However, point-by-point SERS mapping is time-consuming, taking minutes to hours for large-scale imaging. Here, we report a wide-field surface-enhanced coherent anti-Stokes Raman scattering (WISE-CARS) microscope for monitoring nanotags in live cells and label-free detection of metabolic mols. The WISE-CARS microscope achieves an imaging speed of 120 fps for a field of view of 130μm x 130μm. By spectral focusing of femtosecond lasers, a hyperspectral WISE-CARS stack of 60 frames can be acquired within 0.5 s, where over 1 million Raman spectra are parallelly recorded with a spectral resoln. of 10 cm-1. As applications, we demonstrate time-lapse, three-dimensional (3D) WISE-CARS imaging of nanotags in live cells as well as label-free detection of adenine released from S. aureus.
- 368Becerril-Castro, I. B.; Calderon, I.; Ockova, J.; Liebel, M.; van Hulst, N. F.; Giannini, V.; Alvarez-Puebla, R. A. Direct Modular Printing of Plasmonic Chemosensors. ACS Appl. Mater. Interfaces 2022, 14, 57165– 57170, DOI: 10.1021/acsami.2c17202Google ScholarThere is no corresponding record for this reference.
- 369Liebel, M.; Calderon, I.; Pazos-Perez, N.; van Hulst, N. F.; Alvarez-Puebla, R. A. Widefield SERS for High-Throughput Nanoparticle Screening. Angewandte Chemie - International Edition 2022, 61, e202200072, DOI: 10.1002/anie.202200072Google ScholarThere is no corresponding record for this reference.
- 370Romo-Herrera, J. M.; Juárez-Moreno, K.; Guerrini, L.; Kang, Y. L.; Feliu, N.; Parak, W. J.; Álvarez-Puebla, R. A. Paper-Based Plasmonic Substrates as Surface-Enhanced Raman Scattering Spectroscopy Platforms for Cell Culture Applications. Materials Today Bio 2021, 11, 100125, DOI: 10.1016/j.mtbio.2021.100125Google ScholarThere is no corresponding record for this reference.
- 371Liebel, M.; Pazos-Perez, N.; van Hulst, N. F.; Alvarez-Puebla, R. A. Surface-enhanced Raman scattering holography. Nat. Nanotechnol. 2020, 15, 1005– 1011, DOI: 10.1038/s41565-020-0771-9Google Scholar371Surface-enhanced Raman scattering holographyLiebel, Matz; Pazos-Perez, Nicolas; van Hulst, Niek F.; Alvarez-Puebla, Ramon A.Nature Nanotechnology (2020), 15 (12), 1005-1011CODEN: NNAABX; ISSN:1748-3387. (Nature Research)Nanometric probes based on surface-enhanced Raman scattering (SERS) are promising candidates for all-optical environmental, biol. and technol. sensing applications with intrinsic quant. mol. specificity. However, the effectiveness of SERS probes depends on a delicate trade-off between particle size, stability and brightness that has so far hindered their wide application in SERS imaging methodologies. In this Article, we introduce holog. Raman microscopy, which allows single-shot three-dimensional single-particle localization. We validate our approach by simultaneously performing Fourier transform Raman spectroscopy of individual SERS nanoparticles and Raman holog., using shearing interferometry to ext. both the phase and the amplitude of wide-field Raman images and ultimately localize and track single SERS nanoparticles inside living cells in three dimensions. Our results represent a step towards multiplexed single-shot three-dimensional concn. mapping in many different scenarios, including live cell and tissue interrogation and complex anti-counterfeiting applications.
- 372Lindquist, N. C.; Brolo, A. G. Ultra-High-Speed Dynamics in Surface-Enhanced Raman Scattering. J. Phys. Chem. C 2021, 125, 7523– 7532, DOI: 10.1021/acs.jpcc.0c11150Google Scholar372Ultra-High-Speed Dynamics in Surface-Enhanced Raman ScatteringLindquist, Nathan C.; Brolo, Alexandre G.Journal of Physical Chemistry C (2021), 125 (14), 7523-7532CODEN: JPCCCK; ISSN:1932-7447. (American Chemical Society)A review. In this perspective, we discuss recent observations related to the temporal dynamics of intensities in surface-enhanced Raman scattering (SERS) expts. SERS is a well-established and highly active research field, driven by the potential of the technique in anal. and bioanal. applications. However, there are several fundamental aspects of the effect that still challenge and fascinate researchers in the area. Here we will focus on the recent observation that strong SERS intensity fluctuations (SIFs) are seen when expts. are performed at fast acquisition rates, even when the metal surface is completely covered by an adsorbate. Interestingly, the SIF dynamics indicate bursts of SERS activities that last only a few hundreds of microseconds, followed by a longer period of inactivity. This type of behavior has been obsd. from several systems and configurations, including single metallic nanoshells and nanostars, immobilized colloidal aggregates, nanoparticle-on-a-mirror configurations, and metal-coated microspheres. This diversity suggests that the dynamical behavior is a fundamental characteristic of the SERS effect. Time-dependent at. rearrangements within the confined environment of the SERS hotspots are suggested as the main mechanism driving these fluctuations. The dynamical SERS behavior, revealed with high-speed acquisitions, should provide a new direction for the study of at. reconstruction and single mol. interactions with metallic nanoenvironments with an unprecedented level of detail.
- 373Mueller, N. S.; Arul, R.; Jakob, L. A.; Blunt, M. O.; Földes, T.; Rosta, E.; Baumberg, J. J. Collective Mid-Infrared Vibrations in Surface-Enhanced Raman Scattering. Nano Lett. 2022, 22, 7254– 7260, DOI: 10.1021/acs.nanolett.2c02806Google Scholar373Collective Mid-Infrared Vibrations in Surface-Enhanced Raman ScatteringMueller, Niclas S.; Arul, Rakesh; Jakob, Lukas A.; Blunt, Matthew Oliver; Foldes, Tamas; Rosta, Edina; Baumberg, Jeremy J.Nano Letters (2022), 22 (17), 7254-7260CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)Surface-enhanced Raman scattering (SERS) is typically assumed to occur at individual mols. neglecting intermol. vibrational coupling. Here, we show instead how collective vibrations from IR (IR) coupled dipoles are seen in SERS from mol. monolayers. Mixing IR-active mols. with IR-inactive spacer mols. controls the intermol. sepn. Intermol. coupling leads to vibrational frequency upshifts up to 8 cm-1, tuning with the mixing fraction and IR dipole strength, in excellent agreement with microscopic models and d. functional theory. These cooperative frequency shifts can be used as a ruler to measure intermol. distance and disorder with angstrom resoln. We demonstrate this for photochem. reactions of 4-nitrothiophenol, which depletes the no. of neighboring IR-active mols. and breaks the collective vibration, enabling direct tracking of the reaction. Collective mol. vibrations reshape SERS spectra and need to be considered in the anal. of vibrational spectra throughout anal. chem. and sensing.
- 374Das, S.; Saxena, K.; Tinguely, J. C.; Pal, A.; Wickramasinghe, N. L.; Khezri, A.; Dubey, V.; Ahmad, A.; Perumal, V.; Ahmad, R.; Wadduwage, D. N.; Ahluwalia, B. S.; Mehta, D. S. SERS Nanowire Chip and Machine Learning-Enabled Classification of Wild-Type and Antibiotic-Resistant Bacteria at Species and Strain Levels. ACS Appl. Mater. Interfaces 2023, 15, 24047– 24058, DOI: 10.1021/acsami.3c00612Google Scholar374SERS Nanowire Chip and Machine Learning-Enabled Classification of Wild-Type and Antibiotic-Resistant Bacteria at Species and Strain LevelsDas, Sathi; Saxena, Kanchan; Tinguely, Jean-Claude; Pal, Arijit; Wickramasinghe, Nima L.; Khezri, Abdolrahman; Dubey, Vishesh; Ahmad, Azeem; Perumal, Vivekanandan; Ahmad, Rafi; Wadduwage, Dushan N.; Ahluwalia, Balpreet Singh; Mehta, Dalip SinghACS Applied Materials & Interfaces (2023), 15 (20), 24047-24058CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Antimicrobial resistance (AMR) is a major health threat worldwide and the culture-based bacterial detection methods are slow. Surface-enhanced Raman spectroscopy (SERS) can be used to identify target analytes in real time with sensitivity down to the single-mol. level, providing a promising soln. for the culture-free bacterial detection. We report the fabrication of SERS substrates having tightly packed silver (Ag) nanoparticles loaded onto long silicon nanowires (Si NWs) grown by the metal-assisted chem. etching (MACE) method for the detection of bacteria. The optimized SERS chips exhibited sensitivity down to 10-12 M concn. of R6G mols. and detected reproducible Raman spectra of bacteria down to a concn. of 100 colony forming units (CFU)/mL, which is a thousand times lower than the clin. threshold of bacterial infections like UTI (105 CFU/mL). A Siamese neural network model was used to classify SERS spectra from bacteria specimens. The trained model identified 12 different bacterial species, including those which are causative agents for tuberculosis and urinary tract infection (UTI). Next, the SERS chips and another Siamese neural network model were used to differentiate AMR strains from susceptible strains of Escherichia coli (E. coli). The enhancement offered by SERS chip-enabled acquisitions of Raman spectra of bacteria directly in the synthetic urine by spiking the sample with only 103 CFU/mL E. coli. Thus, the present study lays the ground for the identification and quantification of bacteria on SERS chips, thereby offering a potential future use for rapid, reproducible, label-free, and low limit detection of clin. pathogens.
- 375Pérez-Jiménez, A. I.; Lyu, D.; Lu, Z.; Liu, G.; Ren, B. Surface-enhanced Raman spectroscopy: benefits, trade-offs and future developments. Chemical Science 2020, 11, 4563– 4577, DOI: 10.1039/D0SC00809EGoogle Scholar375Surface-enhanced Raman spectroscopy: benefits, trade-offs and future developmentsPerez-Jimenez, Ana Isabel; Lyu, Danya; Lu, Zhixuan; Liu, Guokun; Ren, BinChemical Science (2020), 11 (18), 4563-4577CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)Surface-enhanced Raman spectroscopy (SERS) is a vibrational spectroscopy technique with sensitivity down to the single mol. level that provides fine mol. fingerprints, allowing for direct identification of target analytes. Extensive theor. and exptl. research, together with continuous development of nanotechnol., has significantly broadened the scope of SERS and made it a hot research field in chem., physics, materials, biomedicine, and so on. However, SERS has not been developed into a routine anal. technique, and continuous efforts have been made to address the problems preventing its real-world application. The present minireview focuses on analyzing current and potential strategies to tackle problems and realize the SERS performance necessary for translation to practical applications.
- 376Zhao, Z.; Bao, H.; Zhao, Q.; Fu, H.; Zhou, L.; Zhang, H.; Li, Y.; Cai, W. Efficient SERS Response of Porous-ZnO-Covered Gold Nanoarray Chips to Trace Benzene-Volatile Organic Compounds. ACS Appl. Mater. Interfaces 2022, 14, 47999– 48010, DOI: 10.1021/acsami.2c11682Google Scholar376Efficient SERS Response of Porous-ZnO-Covered Gold Nanoarray Chips to Trace Benzene-Volatile Organic CompoundsZhao, Zhipeng; Bao, Haoming; Zhao, Qian; Fu, Hao; Zhou, Le; Zhang, Hongwen; Li, Yue; Cai, WeipingACS Applied Materials & Interfaces (2022), 14 (42), 47999-48010CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Fast and sensitive detection of gaseous volatile org. compds. (VOCs), based on surface-enhanced Raman spectroscopy (SERS), is still a challenge due to their weak interaction with plasmonic metals and overly small Raman scattering cross sections. Herein, we propose a simple strategy to achieve the SERS-based highly efficient detection of trace benzene-VOCs (B-VOCs) based on a composite chip. The composite chip is designed and fabricated via covering the porous zinc oxide on gold nanoarrays by a one-step soln. growth method. Such composite chip shows highly selective capture of gaseous B-VOCs (benzene, toluene, nitrobenzene, xylene, and chlorobenzene, etc.), which leads to the rapid and sensitive SERS responses to them. Typically, this chip can response to gaseous toluene within 30 s, and the lowest detectable concn. is below 10 ppb. Further expts. have revealed that there exists an optimal thickness of the ZnO covering layer for the highly efficient SERS response to the B-VOCs, which is about 150 nm. Also, such a composite chip is recoverable in SERS response and hence reusable. The highly efficient SERS response of the composite chip to the B-VOCs is attributed to the porous structure-enhanced mol. adsorption and the electromagnetic-chem. dual-enhancement mechanism. This work not only presents a practical SERS chip for the efficient detection of the typical B-VOCs but also provides a deep understand the interaction between the B-VOCs and the ZnO as well as the chem. enhancement mechanism.
- 377Rodriguez-Nieves, A. L.; Taylor, M. L.; Wilson, R.; Eldridge, B. K.; Nawalage, S.; Annamer, A.; Miller, H. G.; Alle, M. R.; Gomrok, S.; Zhang, D.; Wang, Y.; Huang, X. Multiplexed Surface Protein Detection and Cancer Classification Using Gap-Enhanced Magnetic-Plasmonic Core-Shell Raman Nanotags and Machine Learning Algorithm. ACS Appl. Mater. Interfaces 2024, 16, 2041– 2057, DOI: 10.1021/acsami.3c13921Google ScholarThere is no corresponding record for this reference.
- 378Kho, K. W.; Dinish, U. S.; Kumar, A.; Olivo, M. Frequency Shifts in SERS for Biosensing. ACS Nano 2012, 6, 4892– 4902, DOI: 10.1021/nn300352bGoogle Scholar378Frequency Shifts in SERS for BiosensingKho, Kiang Wei; Dinish, U. S.; Kumar, Anil; Olivo, MaliniACS Nano (2012), 6 (6), 4892-4902CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)The authors report an observation of a peculiar effect in which the vibrational frequencies of antibody-conjugated SERS-active reporter mols. are shifted in quant. correlation with the concn. of the targeted antigen. The authors attribute the frequency shifts to mech. perturbations in the antibody-reporter complex, as a result of antibody-antigen interaction forces. The authors' observation thus demonstrates the potentiality of an antibody-conjugated SERS-active reporter complex as a SERS-active nanomech. sensor for biodetection. Remarkably, the authors' sensing scheme, despite employing only one antibody, is able to achieve detection sensitivity comparable to that of a conventional sandwich immunoassay. Addnl., the authors have carried out a proof-of-concept study into using multiple 'stress-sensitive' SERS reporters for multiplexed detection of antigen-antibody bindings at the subdiffraction limit. The current work could therefore pave the way to realizing a label-free high-d. protein nanoarray.
- 379Langer, J.; Jimenez de Aberasturi, D.; Aizpurua, J.; Alvarez-Puebla, R. A.; Auguié, B.; Baumberg, J. J.; Bazan, G. C.; Bell, S. E. J.; Boisen, A.; Brolo, A. G.; Choo, J.; Cialla-May, D.; Deckert, V.; Fabris, L.; Faulds, K.; García de Abajo, F. J.; Goodacre, R.; Graham, D.; Haes, A. J.; Haynes, C. L.; Huck, C.; Itoh, T.; Käll, M.; Kneipp, J.; Kotov, N. A.; Kuang, H.; Le Ru, E. C.; Lee, H. K.; Li, J.-F.; Ling, X. Y.; Maier, S. A.; Mayerhöfer, T.; Moskovits, M.; Murakoshi, K.; Nam, J.-M.; Nie, S.; Ozaki, Y.; Pastoriza-Santos, I.; Perez-Juste, J.; Popp, J.; Pucci, A.; Reich, S.; Ren, B.; Schatz, G. C.; Shegai, T.; Schlücker, S.; Tay, L.-L.; Thomas, K. G.; Tian, Z.-Q.; Van Duyne, R. P.; Vo-Dinh, T.; Wang, Y.; Willets, K. A.; Xu, C.; Xu, H.; Xu, Y.; Yamamoto, Y. S.; Zhao, B.; Liz-Marzán, L. M. Present and Future of Surface-Enhanced Raman Scattering. ACS Nano 2020, 14, 28– 117, DOI: 10.1021/acsnano.9b04224Google Scholar379Present and Future of Surface-Enhanced Raman ScatteringLanger, Judith; Jimenez de Aberasturi, Dorleta; Aizpurua, Javier; Alvarez-Puebla, Ramon A.; Auguie, Baptiste; Baumberg, Jeremy J.; Bazan, Guillermo C.; Bell, Steven E. J.; Boisen, Anja; Brolo, Alexandre G.; Choo, Jaebum; Cialla-May, Dana; Deckert, Volker; Fabris, Laura; Faulds, Karen; Garcia de Abajo, F. Javier; Goodacre, Royston; Graham, Duncan; Haes, Amanda J.; Haynes, Christy L.; Huck, Christian; Itoh, Tamitake; Kall, Mikael; Kneipp, Janina; Kotov, Nicholas A.; Kuang, Hua; Le Ru, Eric C.; Lee, Hiang Kwee; Li, Jian-Feng; Ling, Xing Yi; Maier, Stefan A.; Mayerhofer, Thomas; Moskovits, Martin; Murakoshi, Kei; Nam, Jwa-Min; Nie, Shuming; Ozaki, Yukihiro; Pastoriza-Santos, Isabel; Perez-Juste, Jorge; Popp, Juergen; Pucci, Annemarie; Reich, Stephanie; Ren, Bin; Schatz, George C.; Shegai, Timur; Schlucker, Sebastian; Tay, Li-Lin; Thomas, K. George; Tian, Zhong-Qun; Van Duyne, Richard P.; Vo-Dinh, Tuan; Wang, Yue; Willets, Katherine A.; Xu, Chuanlai; Xu, Hongxing; Xu, Yikai; Yamamoto, Yuko S.; Zhao, Bing; Liz-Marzan, Luis M.ACS Nano (2020), 14 (1), 28-117CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)A review. The discovery of the enhancement of Raman scattering by mols. adsorbed on nanostructured metal surfaces is a landmark in the history of spectroscopic and anal. techniques. Significant exptl. and theor. effort has been directed toward understanding the surface-enhanced Raman scattering (SERS) effect and demonstrating its potential in various types of ultrasensitive sensing applications in a wide variety of fields. In the 45 years since its discovery, SERS has blossomed into a rich area of research and technol., but addnl. efforts are still needed before it can be routinely used anal. and in com. products. In this Review, prominent authors from around the world joined together to summarize the state of the art in understanding and using SERS and to predict what can be expected in the near future in terms of research, applications, and technol. development. This Review is dedicated to SERS pioneer and our coauthor, the late Prof. Richard Van Duyne, whom we lost during the prepn. of this article.
- 380Song, C.; Jiang, X.; Yang, Y.; Zhang, J.; Larson, S.; Zhao, Y.; Wang, L. High-Sensitive Assay of Nucleic Acid Using Tetrahedral DNA Probes and DNA Concatamers with a Surface-Enhanced Raman Scattering/Surface Plasmon Resonance Dual-Mode Biosensor Based on a Silver Nanorod-Covered Silver Nanohole Array. ACS Appl. Mater. Interfaces 2020, 12, 31242– 31254, DOI: 10.1021/acsami.0c08453Google Scholar380High-Sensitive Assay of Nucleic Acid Using Tetrahedral DNA Probes and DNA Concatamers with a Surface-Enhanced Raman Scattering/Surface Plasmon Resonance Dual-Mode Biosensor Based on a Silver Nanorod-Covered Silver Nanohole ArraySong, Chunyuan; Jiang, Xinyu; Yang, Yanjun; Zhang, Jingjing; Larson, Steven; Zhao, Yiping; Wang, LianhuiACS Applied Materials & Interfaces (2020), 12 (28), 31242-31254CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)A novel surface-enhanced Raman scattering/surface plasmon resonance (SERS/SPR) dual-mode biosensor prepd. on a silver nanorod-covered silver nanohole (Ag NR-NH) array by surface modification of tetrahedral DNA probes is proposed for highly sensitive detecting nucleic acids by a special signal amplification strategy of DNA supersandwich. The Ag NR-NH with a large area and uniformly arrayed nanostructure possesses excellent anisotropic extraordinary optical transmission and strong localized surface plasmon resonance, which lead to sensitive SPR response to the change of a local refractive index and strong localized elec. fields for excellent SERS activity. To obtain high sensitivity and specificity, smart tetrahedral DNA probes are immobilized onto the Ag NR-NH array and the DNA supersandwich sensing strategy, including the signal amplification of DNA concatamers, was used. About 10 times signal enhancement for SPR and 4 times for SERS are achieved by this sensing strategy. In the detection of the target DNA in the human serum, the two sensing modes have complementary performances, i.e., the limit of detection for the SPR array is high (0.51 pM), while for SERS, it is low (0.77 fM), but the specificity for SPR is much higher than that of SERS. This improves the robustness of the DNA sensors, and subsequent recovery tests also confirm good reliability of the biosensor. The proposed SERS/SPR dual-mode biosensor has a great potential for high performance and reliable detection of trace disease-related nucleic acid biomarkers in the serum and is a powerful sensing platform for early-stage disease diagnosis.
- 381Tseng, Y. M.; Chen, K. L.; Chao, P. H.; Han, Y. Y.; Huang, N. T. Deep Learning-Assisted Surface-Enhanced Raman Scattering for Rapid Bacterial Identification. ACS Appl. Mater. Interfaces 2023, 15, 26398– 26406, DOI: 10.1021/acsami.3c03212Google ScholarThere is no corresponding record for this reference.
- 382Leong, S. X.; Koh, L. K.; Koh, C. S. L.; Phan-Quang, G. C.; Lee, H. K.; Ling, X. Y. In Situ Differentiation of Multiplex Noncovalent Interactions Using SERS and Chemometrics. ACS Appl. Mater. Interfaces 2020, 12, 33421– 33427, DOI: 10.1021/acsami.0c08053Google Scholar382In Situ Differentiation of Multiplex Noncovalent Interactions Using SERS and ChemometricsLeong, Shi Xuan; Koh, Li Keng; Koh, Charlynn Sher Lin; Phan-Quang, Gia Chuong; Lee, Hiang Kwee; Ling, Xing YiACS Applied Materials & Interfaces (2020), 12 (29), 33421-33427CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Probing changes of noncovalent interactions is crucial to study the binding efficiencies and strengths of (bio)mol. complexes. While surface-enhanced Raman scattering (SERS) offers unique mol. fingerprints to examine such interactions in situ, current platforms are only able to recognize hydrogen bonds because of their reliance on manual spectral identification. Here, the authors differentiate multiple intermol. interactions between two interacting species by synergizing plasmonic liq. marble-based SERS platforms, chemometrics, and d. functional theory. Characteristic 3-mercaptobenzoic acid (probe) Raman signals have distinct peak shifts upon hydrogen bonding and ionic interactions with tert-butylamine, a model interacting species. Notably, the authors further quantify the contributions from each noncovalent interaction coexisting in different proportions. As a proof-of-concept, the authors detect and categorize biol. important nucleotide bases based on mol.-specific interactions. This will potentially be useful to study how subtle changes in biomol. interactions affect their structural and binding properties.
- 383Ma, H.; Liu, S.; Zheng, N.; Liu, Y.; Han, X. X.; He, C.; Lu, H.; Zhao, B. Frequency Shifts in Surface-Enhanced Raman Spectroscopy-Based Immunoassays: Mechanistic Insights and Application in Protein Carbonylation Detection. Anal. Chem. 2019, 91, 9376– 9381, DOI: 10.1021/acs.analchem.9b02640Google Scholar383Frequency Shifts in Surface-Enhanced Raman Spectroscopy-Based Immunoassays: Mechanistic Insights and Application in Protein Carbonylation DetectionMa, Hao; Liu, Songlin; Zheng, Naiqing; Liu, Yawen; Han, Xiao Xia; He, Chengyan; Lu, Hui; Zhao, BingAnalytical Chemistry (Washington, DC, United States) (2019), 91 (15), 9376-9381CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Frequency-shift based surface-enhanced Raman spectroscopy (SERS) has exhibited great potential applications in bioanal. chem. and biomedicine in recent years. The basis and the crucial factors detg. frequency shifts are, however, still unclear. Herein, the authors have systematically investigated how solvents, antigens, and antibodies affect the band shifts in SERS-based immunoassays. By applying the charge transfer theory together with the Stark effect and time-dependent d. functional theory (TDDFT) calcn., mechanistic insights into the frequency shifts in immunoreactions is proposed and discussed in detail. Accordingly, the exptl. condition is further optimized and is successfully applied for the first time to detect carbonylated proteins, promising diagnostic biomarkers for human diseases. This study provides theor. guidance for designing SERS frequency shift-based immunoassays and paves a new avenue for further applications of the strategy in clin. diagnosis.
- 384Guo, S.; Popp, J.; Bocklitz, T. Chemometric analysis in Raman spectroscopy from experimental design to machine learning-based modeling. Nat. Protoc 2021, 16, 5426– 5459, DOI: 10.1038/s41596-021-00620-3Google Scholar384Chemometric analysis in Raman spectroscopy from experimental design to machine learning-based modelingGuo, Shuxia; Popp, Jurgen; Bocklitz, ThomasNature Protocols (2021), 16 (12), 5426-5459CODEN: NPARDW; ISSN:1750-2799. (Nature Portfolio)Abstr.: Raman spectroscopy is increasingly being used in biol., forensics, diagnostics, pharmaceutics and food science applications. This growth is triggered not only by improvements in the computational and exptl. setups but also by the development of chemometric techniques. Chemometric techniques are the anal. processes used to detect and ext. information from subtle differences in Raman spectra obtained from related samples. This information could be used to find out, for example, whether a mixt. of bacterial cells contains different species, or whether a mammalian cell is healthy or not. Chemometric techniques include spectral processing (ensuring that the spectra used for the subsequent computational processes are as clean as possible) as well as the statistical anal. of the data required for finding the spectral differences that are most useful for differentiation between, for example, different cell types. For Raman spectra, this anal. process is not yet standardized, and there are many confounding pitfalls. This protocol provides guidance on how to perform a Raman spectral anal.: how to avoid these pitfalls, and strategies to circumvent problematic issues. The protocol is divided into four parts: exptl. design, data preprocessing, data learning and model transfer. We exemplify our workflow using three example datasets where the spectra from individual cells were collected in single-cell mode, and one dataset where the data were collected from a raster scanning-based Raman spectral imaging expt. of mice tissue. Our aim is to help move Raman-based technologies from proof-of-concept studies toward real-world applications.
- 385Lee, H. K.; Koh, C. S.; Lo, W.-S.; Liu, Y.; Phang, I. Y.; Sim, H. Y.; Lee, Y. H.; Phan-Quang, G. C.; Han, X.; Tsung, C.-K.; Ling, X. Y. Applying a Nanoparticle@MOF Interface To Activate an Unconventional Regioselectivity of an Inert Reaction at Ambient Conditions. J. Am. Chem. Soc. 2020, 142, 11521– 11527, DOI: 10.1021/jacs.0c04144Google Scholar385Applying a Nanoparticle@MOF Interface To Activate an Unconventional Regioselectivity of an Inert Reaction at Ambient ConditionsLee, Hiang Kwee; Koh, Charlynn Sher; Lo, Wei-Shang; Liu, Yejing; Phang, In Yee; Sim, Howard Yi; Lee, Yih Hong; Phan-Quang, Gia Chuong; Han, Xuemei; Tsung, Chia-Kuang; Ling, Xing YiJournal of the American Chemical Society (2020), 142 (26), 11521-11527CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Here we design an interface between a metal nanoparticle (NP) and a metal-org. framework (MOF) to activate an inert CO2 carboxylation reaction and in situ monitor its unconventional regioselectivity at the mol. level. Using a Kolbe-Schmitt reaction as model, our strategy exploits the NP@MOF interface to create a pseudo high-pressure CO2 microenvironment over the phenolic substrate to drive its direct C-H carboxylation at ambient conditions. Conversely, Kolbe-Schmitt reactions usually demand high reaction temp. (>125°C) and pressure (>80 atm). Notably, we observe an unprecedented CO2 meta-carboxylation of an arene that was previously deemed impossible in traditional Kolbe-Schmitt reactions. While the phenolic substrate in this study is fixed at the NP@MOF interface to facilitate spectroscopic investigations, free reactants could be activated the same way by the local pressurized CO2 microenvironment. These valuable insights create enormous opportunities in diverse applications including synthetic chem., gas valorization, and greenhouse gas remediation.
- 386Ehrentreich, F.; Sümmchen, L. Spike removal and denoising of Raman spectra by wavelet transform methods. Anal. Chem. 2001, 73, 4364– 4373, DOI: 10.1021/ac0013756Google Scholar386Spike Removal and Denoising of Raman Spectra by Wavelet Transform MethodsEhrentreich, F.; Suemmchen, L.Analytical Chemistry (2001), 73 (17), 4364-4373CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Wavelet decompns. of Raman spectra were studied with respect to their usability for spike removal and denoising of the raw data. Those operations should be performed sequentially. Suppression of spikes is not straightforwardly possible by wavelet transformation; however, the wavelet transform may be used to recognize the spikes by their 1st level detail coeffs. Spike locations could be projected from the details to the approxns. and, further, to appropriate locations of the original spectrum. After spike recognition, those regions will be replaced by interpolated values. To complete processing, denoising is performed with the despiked spectrum by repeated application of wavelet transform methods.
- 387Phillips, G. R.; Harris, J. M. Polynomial filters for data sets with outlying or missing observations: application to charge-coupled-device-detected Raman spectra contaminated by cosmic rays. Anal. Chem. 1990, 62, 2351– 2357, DOI: 10.1021/ac00220a017Google Scholar387Polynomial filters for data sets with outlying or missing observations: application to charge-coupled-device-detected Raman spectra contaminated by cosmic raysPhillips, G. R.; Harris, Joel M.Analytical Chemistry (1990), 62 (21), 2351-7CODEN: ANCHAM; ISSN:0003-2700.Occasionally data sets contain points with excess error so that no information about the underlying signal is available from these observations. Such points should be considered lost and be given no influence on the results. Polynomial filters suitable for smoothing data sets contg. outlying or missing observations are presented. Outliers are 1st identified by their deviation from the trends of the surrounding data, relative to a robust est. of the std. deviation. In the vicinity of an outlying point thus identified, the missing-point filter employs a polynomial fit to the points surrounding, but not including, the outlying or missing point. In the absence of outliers, the procedure reverts to ordinary Savitzky-Golay polynomial filtering. The equations for generating these filters and predicting their statistical properties were derived. Their performance was evaluated on CCD-detected Raman spectra contaminated with cosmic ray events and was compared with nonlinear smoothing algorithms. The linear, missing-point polynomial filters are efficient, both in speed and in ability to bridge gaps in data with minimal distortion.
- 388Guo, S.; Beleites, C.; Neugebauer, U.; Abalde-Cela, S.; Afseth, N. K.; Alsamad, F.; Anand, S.; Araujo-Andrade, C.; Aškrabić, S.; Avci, E.; Baia, M.; Baranska, M.; Baria, E.; Batista de Carvalho, L. A. E.; de Bettignies, P.; Bonifacio, A.; Bonnier, F.; Brauchle, E. M.; Byrne, H. J.; Chourpa, I.; Cicchi, R.; Cuisinier, F.; Culha, M.; Dahms, M.; David, C.; Duponchel, L.; Duraipandian, S.; El-Mashtoly, S. F.; Ellis, D. I.; Eppe, G.; Falgayrac, G.; Gamulin, O.; Gardner, B.; Gardner, P.; Gerwert, K.; Giamarellos-Bourboulis, E. J.; Gizurarson, S.; Gnyba, M.; Goodacre, R.; Grysan, P.; Guntinas-Lichius, O.; Helgadottir, H.; Grošev, V. M.; Kendall, C.; Kiselev, R.; Kölbach, M.; Krafft, C.; Krishnamoorthy, S.; Kubryck, P.; Lendl, B.; Loza-Alvarez, P.; Lyng, F. M.; Machill, S.; Malherbe, C.; Marro, M.; Marques, M. P. M.; Matuszyk, E.; Morasso, C. F.; Moreau, M.; Muhamadali, H.; Mussi, V.; Notingher, I.; Pacia, M. Z.; Pavone, F. S.; Penel, G.; Petersen, D.; Piot, O.; Rau, J. V.; Richter, M.; Rybarczyk, M. K.; Salehi, H.; Schenke-Layland, K.; Schlücker, S.; Schosserer, M.; Schütze, K.; Sergo, V.; Sinjab, F.; Smulko, J.; Sockalingum, G. D.; Stiebing, C.; Stone, N.; Untereiner, V.; Vanna, R.; Wieland, K.; Popp, J.; Bocklitz, T. Comparability of Raman Spectroscopic Configurations: A Large Scale Cross-Laboratory Study. Anal. Chem. 2020, 92, 15745– 15756, DOI: 10.1021/acs.analchem.0c02696Google Scholar388Comparability of Raman Spectroscopic Configurations: A Large Scale Cross-Laboratory StudyGuo, Shuxia; Beleites, Claudia; Neugebauer, Ute; Abalde-Cela, Sara; Afseth, Nils Kristian; Alsamad, Fatima; Anand, Suresh; Araujo-Andrade, Cuauhtemoc; Askrabic, Sonja; Avci, Ertug; Baia, Monica; Baranska, Malgorzata; Baria, Enrico; Batista de Carvalho, Luis A. E.; de Bettignies, Philippe; Bonifacio, Alois; Bonnier, Franck; Brauchle, Eva Maria; Byrne, Hugh J.; Chourpa, Igor; Cicchi, Riccardo; Cuisinier, Frederic; Culha, Mustafa; Dahms, Marcel; David, Catalina; Duponchel, Ludovic; Duraipandian, Shiyamala; El-Mashtoly, Samir F.; Ellis, David I.; Eppe, Gauthier; Falgayrac, Guillaume; Gamulin, Ozren; Gardner, Benjamin; Gardner, Peter; Gerwert, Klaus; Giamarellos-Bourboulis, Evangelos J.; Gizurarson, Sveinbjorn; Gnyba, Marcin; Goodacre, Royston; Grysan, Patrick; Guntinas-Lichius, Orlando; Helgadottir, Helga; Grosev, Vlasta Mohacek; Kendall, Catherine; Kiselev, Roman; Koelbach, Micha; Krafft, Christoph; Krishnamoorthy, Sivashankar; Kubryck, Patrick; Lendl, Bernhard; Loza-Alvarez, Pablo; Lyng, Fiona M.; Machill, Susanne; Malherbe, Cedric; Marro, Monica; Marques, Maria Paula M.; Matuszyk, Ewelina; Morasso, Carlo Francesco; Moreau, Myriam; Muhamadali, Howbeer; Mussi, Valentina; Notingher, Ioan; Pacia, Marta Z.; Pavone, Francesco S.; Penel, Guillaume; Petersen, Dennis; Piot, Olivier; Rau, Julietta V.; Richter, Marc; Rybarczyk, Maria Krystyna; Salehi, Hamideh; Schenke-Layland, Katja; Schluecker, Sebastian; Schosserer, Markus; Schuetze, Karin; Sergo, Valter; Sinjab, Faris; Smulko, Janusz; Sockalingum, Ganesh D.; Stiebing, Clara; Stone, Nick; Untereiner, Valerie; Vanna, Renzo; Wieland, Karin; Popp, Juergen; Bocklitz, ThomasAnalytical Chemistry (Washington, DC, United States) (2020), 92 (24), 15745-15756CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)The variable configuration of Raman spectroscopic platforms is one of the major obstacles in establishing Raman spectroscopy as a valuable physicochem. method within real-world scenarios such as clin. diagnostics. For such real world applications like diagnostic classification, the models should ideally be usable to predict data from different setups. Whether it is done by training a rugged model with data from many setups or by a primary-replica strategy where models are developed on a 'primary' setup and the test data are generated on 'replicate' setups, this is only possible if the Raman spectra from different setups are consistent, reproducible, and comparable. However, Raman spectra can be highly sensitive to the measurement conditions, and they change from setup to setup even if the same samples are measured. Although increasingly recognized as an issue, the dependence of the Raman spectra on the instrumental configuration is far from being fully understood and great effort is needed to address the resulting spectral variations and to correct for them. To make the severity of the situation clear, we present a round robin expt. investigating the comparability of 35 Raman spectroscopic devices with different configurations in 15 institutes within seven European countries from the COST (European Cooperation in Science and Technol.) action Raman4clinics. The expt. was developed in a fashion that allows various instrumental configurations ranging from highly confocal setups to fiber-optic based systems with different excitation wavelengths. We illustrate the spectral variations caused by the instrumental configurations from the perspectives of peak shifts, intensity variations, peak widths, and noise levels. We conclude this contribution with recommendations that may help to improve the inter-lab. studies.
- 389Jiang, X.; Yang, M.; Meng, Y.; Jiang, W.; Zhan, J. Cysteamine-Modified Silver Nanoparticle Aggregates for Quantitative SERS Sensing of Pentachlorophenol with a Portable Raman Spectrometer. ACS Appl. Mater. Interfaces 2013, 5, 6902– 6908, DOI: 10.1021/am401718pGoogle Scholar389Cysteamine-Modified Silver Nanoparticle Aggregates for Quantitative SERS Sensing of Pentachlorophenol with a Portable Raman SpectrometerJiang, Xiaohong; Yang, Min; Meng, Yanjing; Jiang, Wei; Zhan, JinhuaACS Applied Materials & Interfaces (2013), 5 (15), 6902-6908CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Cysteamine-modified silver nanoparticle aggregates has been fabricated for pentachlorophenol (PCP) sensing by surface-enhanced Raman spectroscopy (SERS) using a portable Raman spectrometer. The cysteamine monolayers could preconc. PCP close to the substrate surface through the electrostatic interaction, which makes the SERS detection of PCP possible. Moreover, the Raman bands of cysteamine could be used as the internal spectral ref. in the quant. anal. Qual. detection of PCP was carried out by SERS without any sample pretreatment. Quant. anal. of PCP was further realized based on the prepd. substrate, as the log-log plot of normalized SERS intensity of PCP vs. its concns. exhibits a good linear relationship. The SERS signals collected on 20 randomly selected points show that the relative std. deviation of the normalized Raman intensity is 5.8%, which indicates the substrate had good uniformity. The PCP sensor also shows good long-term stability in the analyte soln. The substrate was cyclic immersed into PCP and methanol soln.; after several cycles, the sensor still had good adsorption to PCP, which revealed the sensor has good reusability. Coupling with a portable Raman spectrometer, the cysteamine-modified silver nanoparticle aggregates have the potential to be used for in situ and routine SERS anal. of PCP in environmental samples.
- 390Lorenz, B.; Guo, S.; Raab, C.; Leisching, P.; Bocklitz, T.; Rösch, P.; Popp, J. Comparison of conventional and shifted excitation Raman difference spectroscopy for bacterial identification. J. Raman Spectrosc. 2022, 53, 1285– 1292, DOI: 10.1002/jrs.6360Google ScholarThere is no corresponding record for this reference.
- 391Kazemzadeh, M.; Martinez-Calderon, M.; Xu, W.; Chamley, L. W.; Hisey, C. L.; Broderick, N. G. R. Cascaded Deep Convolutional Neural Networks as Improved Methods of Preprocessing Raman Spectroscopy Data. Anal. Chem. 2022, 94, 12907– 12918, DOI: 10.1021/acs.analchem.2c03082Google Scholar391Cascaded Deep Convolutional Neural Networks as Improved Methods of Preprocessing Raman Spectroscopy DataKazemzadeh, Mohammadrahim; Martinez-Calderon, Miguel; Xu, Weiliang; Chamley, Lawrence W.; Hisey, Colin L.; Broderick, Neil G. R.Analytical Chemistry (Washington, DC, United States) (2022), 94 (37), 12907-12918CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Machine learning has had a significant impact on the value of spectroscopic characterization tools, particularly in biomedical applications, due to its ability to detect latent patterns within complex spectral data. However, it often requires extensive data preprocessing, including baseline correction and denoising, which can lead to an unintentional bias during classification. To address this, we developed two deep learning methods capable of fully preprocessing raw Raman spectroscopy data without any human input. First, cascaded deep convolutional neural networks (CNN) based on either ResNet or U-Net architectures were trained on randomly generated spectra with augmented defects. Then, they were tested using simulated Raman spectra, surface-enhanced Raman spectroscopy (SERS) imaging of chem. species, low resoln. Raman spectra of human bladder cancer tissue, and finally, classification of SERS spectra from human placental extracellular vesicles (EVs). Both approaches resulted in faster training and complete spectral preprocessing in a single step, with more speed, defect tolerance, and classification accuracy compared to conventional methods. These findings indicate that cascaded CNN preprocessing is ideal for biomedical Raman spectroscopy applications in which large nos. of heterogeneous spectra with diverse defects need to be automatically, rapidly, and reproducibly preprocessed.
- 392Cerjan, B.; Yang, X.; Nordlander, P.; Halas, N. J. Asymmetric Aluminum Antennas for Self-Calibrating Surface-Enhanced Infrared Absorption Spectroscopy. ACS Photonics 2016, 3, 354– 360, DOI: 10.1021/acsphotonics.6b00024Google Scholar392Asymmetric Aluminum Antennas for Self-Calibrating Surface-Enhanced Infrared Absorption SpectroscopyCerjan, Benjamin; Yang, Xiao; Nordlander, Peter; Halas, Naomi J.ACS Photonics (2016), 3 (3), 354-360CODEN: APCHD5; ISSN:2330-4022. (American Chemical Society)While there was a tremendous increase of recent interest in noble metal-based antennas as substrates for surface-enhanced IR absorption spectroscopy, more abundant and manufacturable metals may offer similar or addnl. opportunities for this mid-IR sensing modality. The feasibility of Al antennas for SEIRA was examd., by designing and fabricating asym. Al cross antennas with nm-scale gaps. The asym. cross design enables the simultaneous detection of multiple IR vibrational resonances over a broad region of the mid-IR spectrum. The presence of the Al2O3 amorphous surface oxide layer passivates the metal antenna structures and enables a straightforward covalent binding chem. for analyte mols. to the antenna through multiple approaches, in this case using carboxylic acid functional groups. The Al-O stretching mode of the oxide can be used as a self-calibration std. to quantify the no. of analyte mols. on the antenna surface.
- 393Wang, Z.; Zhang, M.; Harrington, P. d. B. Comparison of Three Algorithms for the Baseline Correction of Hyphenated Data Objects. Anal. Chem. 2014, 86, 9050– 9057, DOI: 10.1021/ac501658kGoogle Scholar393Comparison of Three Algorithms for the Baseline Correction of Hyphenated Data ObjectsWang, Zhengfang; Zhang, Mengliang; Harrington, Peter de B.Analytical Chemistry (Washington, DC, United States) (2014), 86 (18), 9050-9057CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Three novel two-way baseline correction algorithms, i.e., orthogonal basis (OB), fuzzy optimal associative memory (FOAM), and polynomial fitting (PF), were evaluated with HPLC-mass spectrometry (HPLC-MS) and gas chromatog./mass spectrometry (GC/MS) data objects. Among these algorithms, both OB and FOAM are two-way baseline correction algorithms, which reconstruct the entire two-way backgrounds from blank data objects, while the PF algorithm is a pseudo-two-way method, which models each ion chromatogram baseline with a third-order polynomial. The performance of baseline correction methods was first evaluated with respect to the signal-to-noise ratios (SNRs) of 4 major peaks of the HPLC-MS total ion current (TIC) chromatograms of celery seed exts. Then, the effect of baseline correction on pattern recognition was evaluated by using 42 two-way headspace (HS) solid phase microextn. (SPME) GC/MS data objects of 7 polychlorinated biphenyl (PCB) mixt. std. solns. Two types of classifiers, i.e., a fuzzy rule-building expert system (FuRES) and partial least-squares-discriminant anal. (PLS-DA) were evaluated in parallel. Bootstrapped Latin partitions (BLPs) were used to give an unbiased and generalized evaluation of the classification accuracy. SNRs of major peaks of the TIC chromatogram representative of two-way HPLC-MS data objects are increased by baseline correction. In addn., higher prediction accuracies can be obtained by performing baseline correction on the entire GC/MS data set prior to pattern recognition. Also proper data transformation is able to improve the performance of baseline correction. This report is the first of two-way baseline correction methods for hyphenated chromatog./mass spectrometry data objects. Both the orthogonal basis and FOAM baseline correction methods are novel inhouse algorithms and are generally effective for two-way baseline correction. Polynomial fitting is a conventional baseline correction method for one-way data objects and is applied to two-way data objects for the first time. It is applicable when blank data objects are unavailable.
- 394Wolf, S.; Domes, R.; Merian, A.; Domes, C.; Frosch, T. Parallelized Raman Difference Spectroscopy for the Investigation of Chemical Interactions. Anal. Chem. 2022, 94, 10346– 10354, DOI: 10.1021/acs.analchem.2c00222Google Scholar394Parallelized Raman Difference Spectroscopy for the Investigation of Chemical InteractionsWolf, Sebastian; Domes, Robert; Merian, Andreas; Domes, Christian; Frosch, TorstenAnalytical Chemistry (Washington, DC, United States) (2022), 94 (29), 10346-10354CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Raman spectroscopy provides an extremely high chem. selectivity. Raman difference spectroscopy is a technique to reveal even the smallest differences that occur due to weak interactions between substances and changes in the mol. structure. To enable parallelized and highly sensitive Raman difference spectroscopy in a microtiter-array, a diffractive optical element, a lens array, and a fiber bundle were integrated into a Raman spectroscopy setup in a unique fashion. The setup was evaluated with a microtiter-array contg. pyridine-water complexes, and subwavenumber changes below the spectrometer's resoln. could be resolved. The spectral changes were emphasized with two-dimensional correlation anal. D. functional theory calcn. and "atoms in mol." anal. were performed to simulate the intermol. long-range interactions between water and pyridine mols. and to get insight into the involved noncovalent interactions, resp. It was found that by the addn. of pyridine, the energy portion of hydrogen bonds to the total complexation energy between pyridine and water reduces. These results demonstrate the unique abilities of the new setup to investigate subtle changes due to biochem. important mol. interactions and opens new avenues to perform drug binding assays and to monitor highly parallelized chem. reactions.
- 395Heraud, P.; Wood, B. R.; Beardall, J.; McNaughton, D. Effects of pre-processing of Raman spectra on in vivo classification of nutrient status of microalgal cells. Journal of Chemometrics 2006, 20, 193– 197, DOI: 10.1002/cem.990Google Scholar395Effects of pre-processing of Raman spectra on in vivo classification of nutrient status of microalgal cellsHeraud, Philip; Wood, Bayden R.; Beardall, John; McNaughton, DonJournal of Chemometrics (2007), 20 (5), 193-197CODEN: JOCHEU; ISSN:0886-9383. (John Wiley & Sons Ltd.)Raman spectra were obtained from cells of the chlorophyte unicellular eukaryotic alga Dunaliella tertiolecta, which had been grown either under nutrient-replete conditions or starved of nitrogen for 4 days. Spectra were rich in bands which could all be attributed to either chlorophyll a or β-carotene. A cursory examn. of the differences between the spectra of replete and starved cells indicated a decline in chlorophyll α and an increase in β-carotene in chlorophytes. Unprocessed spectra showed pronounced baseline effects. A variety of pre-processing techniques were used in an attempt to visualize the spectral, and hence chem., differences in the transformed data and perform classification based upon these differences. Six types of spectral pre-processing were compared: baseline correction with vector normalization; Multiplicative Scatter Correction (MSC), Extended Multiplicative Signal Correction (EMSC); Std. Normal Variate (SNV); and vector normalized 1st and 2nd deriv. spectra. Results for Soft Independent Modeling of Class Analogy (SIMCA) and Partial Least Squares (PLS) discriminant anal. were compared. All pre-processing methods allowed spectral differences between N-replete and N-starved spectra to be visualized, with derivs. and EMSC scoring the lowest RMSEC and RMSEV values with PLS and also the best overall classification results. SIMCA was not suited to classifying the nutrient classes under any of the pre-treatments, due to the small model distances involved.
- 396Nguyen, C. Q.; Thrift, W. J.; Bhattacharjee, A.; Ranjbar, S.; Gallagher, T.; Darvishzadeh-Varcheie, M.; Sanderson, R. N.; Capolino, F.; Whiteson, K.; Baldi, P.; Hochbaum, A. I.; Ragan, R. Longitudinal Monitoring of Biofilm Formation via Robust Surface-Enhanced Raman Scattering Quantification of Pseudomonas aeruginosa-Produced Metabolites. ACS Appl. Mater. Interfaces 2018, 10, 12364– 12373, DOI: 10.1021/acsami.7b18592Google Scholar396Longitudinal Monitoring of Biofilm Formation via Robust Surface-Enhanced Raman Scattering Quantification of Pseudomonas aeruginosa-Produced MetabolitesNguyen, Cuong Quoc; Thrift, William John; Bhattacharjee, Arunima; Ranjbar, Saba; Gallagher, Tara; Darvishzadeh-Varcheie, Mahsa; Sanderson, Robert Noboru; Capolino, Filippo; Whiteson, Katrine; Baldi, Pierre; Hochbaum, Allon I.; Ragan, ReginaACS Applied Materials & Interfaces (2018), 10 (15), 12364-12373CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Detection of bacterial metabolites at low concns. in fluids with complex background allows for applications ranging from detecting biomarkers of respiratory infections to identifying contaminated medical instruments. Surface-enhanced Raman scattering (SERS) spectroscopy, when utilizing plasmonic nanogaps, has the relatively unique capacity to reach trace mol. detection limits in a label-free format, yet large-area device fabrication incorporating nanogaps with this level of performance has proven difficult. Here, the authors demonstrate the advantages of using chem. assembly to fabricate SERS surfaces with controlled nanometer gap spacings between plasmonic nanospheres. Control of nanogap spacings via the length of the chem. crosslinker provides uniform SERS signals, exhibiting detection of pyocyanin, a secondary metabolite of Pseudomonas aeruginosa, in aq. media at concn. of 100 pg·mL-1. When using machine learning algorithms to analyze the SERS data of the conditioned medium from a bacterial culture, having a more complex background, the authors achieve 1 ng·mL-1 limit of detection of pyocyanin and robust quantification of concn. spanning 5 orders of magnitude. Nanogaps are also incorporated in an in-line microfluidic device, enabling longitudinal monitoring of P. aeruginosa biofilm formation via rapid pyocyanin detection in a medium effluent as early as 3 h after inoculation and quantification in under 9 h. Surface-attached bacteria exposed to a bactericidal antibiotic were differentially less susceptible after 10 h of growth, indicating that these devices may be useful for early intervention of bacterial infections.
- 397Tang, Y.; Zhuang, Y.; Zhang, S.; Smith, Z. J.; Li, Y.; Mu, X.; Li, M.; He, C.; Zheng, X.; Pan, F.; Gao, T.; Zhang, L. Azo-Enhanced Raman Scattering for Enhancing the Sensitivity and Tuning the Frequency of Molecular Vibrations. ACS Central Science 2021, 7, 768– 780, DOI: 10.1021/acscentsci.1c00117Google ScholarThere is no corresponding record for this reference.
- 398Zheng, X.; Yan, X.; Ma, J.; Yao, X.; Zhang, J.; Wang, L. Unidirectional/Bidirectional Electron Transfer at the Au/TiO2 Interface Operando Tracked by SERS Spectra from Au and TiO2. ACS Appl. Mater. Interfaces 2021, 13, 16498– 16506, DOI: 10.1021/acsami.1c02540Google Scholar398Unidirectional/Bidirectional Electron Transfer at the Au/TiO2 Interface Operando Tracked by SERS Spectra from Au and TiO2Zheng, Xinlu; Yan, Xuefeng; Ma, Jiayu; Yao, Xinyun; Zhang, Jinlong; Wang, LingzhiACS Applied Materials & Interfaces (2021), 13 (14), 16498-16506CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Although it is well-known that the size can influence the surface plasmon resonance property of coinage metals and the electronic state of the Mott-Schottky junction formed at the metal/semiconductor interface, insights into how the size can be exploited to optimize the photocatalytic activity and selectivity of metal/semiconductor composites are lacking. Here, we utilize operando SERS spectroscopy to identify the size effect on the electron-transfer dynamics and the direction at the Au/TiO2 interface. This effect was characterized by the photocatalytic redn. sites of p-nitrothiophenol, which were self-tracked with the SERS spectra from Au nanoparticle and inverse-opal structured TiO2, resp. The size-dependent unidirectional/bidirectional transfer of photoinduced electrons at the Au/TiO2 interface was revealed by operando SERS spectroscopy, which enables the rational tuning of the redn. selectivity.
- 399Razzell-Hollis, J.; Thiburce, Q.; Tsoi, W. C.; Kim, J. S. Interfacial Chemical Composition and Molecular Order in Organic Photovoltaic Blend Thin Films Probed by Surface-Enhanced Raman Spectroscopy. ACS Appl. Mater. Interfaces 2016, 8, 31469– 31481, DOI: 10.1021/acsami.6b12124Google ScholarThere is no corresponding record for this reference.
- 400Zeng, Y.; Ananth, R.; Dill, T. J.; Rodarte, A.; Rozin, M. J.; Bradshaw, N.; Brown, E. R.; Tao, A. R. Metasurface-Enhanced Raman Spectroscopy (mSERS) for Oriented Molecular Sensing. ACS Appl. Mater. Interfaces 2022, 14, 32598– 32607, DOI: 10.1021/acsami.2c01656Google Scholar400Metasurface-Enhanced Raman Spectroscopy (mSERS) for Oriented Molecular SensingZeng, Yuan; Ananth, Riddhi; Dill, Tyler J.; Rodarte, Andrea; Rozin, Matthew J.; Bradshaw, Nathan; Brown, Eric R.; Tao, Andrea R.ACS Applied Materials & Interfaces (2022), 14 (28), 32598-32607CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Surface-enhanced Raman spectroscopy (SERS) is a widely used sensing technique for ultrasensitivity chem. sensing, biomedical detection, and environmental anal. Because SERS signal is proportional to the fourth power of the local elec. field, several SERS applications have focused on the design of plasmonic nanogaps to take advantage of the extremely strong near-field enhancement that results from plasmonic coupling, but few designs have focused on how SERS detection is affected by mol. orientation within these nanogaps. Here, we demonstrate a nanoparticle-on-metal metasurface designed for near-perfect optical absorption as a platform for Raman detection of highly oriented mol. analytes, including two-dimensional materials and arom. mols. This metasurface platform overcomes challenges in nanoparticle aggregation, which commonly leads to low or fluctuating Raman signals in other colloidal nanoparticle platforms. Our metasurface-enhanced Raman spectroscopy (mSERS) platform is based on a colloidal Langmuir-Schaefer deposition, with up to 32% surface coverage d. of nanogaps across an entire sensor chip. In this work, we perform both simulations of the local elec. field and exptl. characterization of the mSERS signal obtained for oriented mol. layers. We then demonstrate this mSERS platform for the quant. detection of the drinking-water toxin polybrominated di-Ph ether (BDE-15), with a limit of detection of 0.25μM under 530μW excitation. This detection limit is comparable to other SERS-based sensors operating at laser powers over 3 orders of magnitude higher, indicating the promise of our mSERS platform for nondestructive and low-level analyte detection.
- 401Yang, G.; Ivanov, I. N.; Ruther, R. E.; Sacci, R. L.; Subjakova, V.; Hallinan, D. T.; Nanda, J. Electrolyte Solvation Structure at Solid-Liquid Interface Probed by Nanogap Surface-Enhanced Raman Spectroscopy. ACS Nano 2018, 12, 10159– 10170, DOI: 10.1021/acsnano.8b05038Google Scholar401Electrolyte Solvation Structure at Solid-Liquid Interface Probed by Nanogap Surface-Enhanced Raman SpectroscopyYang, Guang; Ivanov, Ilia N.; Ruther, Rose E.; Sacci, Robert L.; Subjakova, Veronika; Hallinan, Daniel T.; Nanda, JagjitACS Nano (2018), 12 (10), 10159-10170CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Understanding the fundamental factors that drive ion solvation structure and transport is key to design high-performance, stable battery electrolytes. Reversible ion solvation and desolvation are crit. to the interfacial charge-transfer process across the solid-liq. interface as well as the resulting stability of the solid electrolyte interphase. Herein, the authors report the study of Li+ salt solvation structure in aprotic soln. in the immediate vicinity (∼20 nm) of the solid electrode-liq. interface using surface-enhanced Raman spectroscopy (SERS) from a Au nanoparticle (Au NP) monolayer. The plasmonic coupling between Au NPs produces strong electromagnetic field enhancement in the gap region, leading to a 5 orders of magnitude increase in Raman intensity for electrolyte components and their mixts. namely, LiPF6, fluoroethylene carbonate, ethylene carbonate, and di-Et carbonate. Further, the authors est. and compare the Li-ion solvation no. derived from SERS, std. Raman spectroscopy, and FTIR spectroscopy expts. to monitor and ascertain the changes in the solvation shell diam. in the confined nanogap region where there is max. enhancement of the elec. field. Findings provide a multimodal spectroscopic approach to gain fundamental insights into the mol. structure of the electrolyte at the solid-liq. interface.
- 402Höller, R. P. M.; Jahn, I. J.; Cialla-May, D.; Chanana, M.; Popp, J.; Fery, A.; Kuttner, C. Biomacromolecular-Assembled Nanoclusters: Key Aspects for Robust Colloidal SERS Sensing. ACS Appl. Mater. Interfaces 2020, 12, 57302– 57313, DOI: 10.1021/acsami.0c16398Google Scholar402Biomacromolecular-Assembled Nanoclusters: Key Aspects for Robust Colloidal SERS SensingHoller Roland P M; Fery Andreas; Kuttner Christian; Jahn Izabella J; Cialla-May Dana; Popp Jurgen; Jahn Izabella J; Cialla-May Dana; Popp Jurgen; Jahn Izabella J; Cialla-May Dana; Popp Jurgen; Chanana Munish; Fery Andreas; Fery Andreas; Kuttner Christian; Kuttner ChristianACS applied materials & interfaces (2020), 12 (51), 57302-57313 ISSN:.Superstructures of gold nanospheres offer augmented surface-enhanced Raman scattering (SERS) activities beyond the limits of their individual building blocks. However, for application as reliable and quantitative colloidal SERS probes, some key aspects need to be considered to combine efficiency and robustness with respect to hotspot excitation, analyte adsorption, signal stability, and colloidal stability. For this purpose, we studied core/satellite superstructures with spherical cores as a simple optically isotropic model system. Superstructures of different core sizes were assembled using bovine serum albumin (BSA), which serves as a non-specific biomacromolecular linker and provides electrosteric stabilization. We show that the "noisy" spectral footprint of the protein coating may serve as an internal standard, which allows accurate monitoring of the adsorption kinetics of analytes. The SERS activity was quantified using 4-mercaptobenzoic acid (MBA) as an aromatic low-molecular-weight model analyte. The molar SERS efficiency was studied by variation of the particle (Au(0)) and analyte concentrations with a limit of detection of 10(-7) M MBA. The practical importance of colloidal stability for robust measurement conditions was demonstrated by comparing the superstructures with their citrate-stabilized or protein-coated building blocks. We explain the theoretical background of hotspot formation by a leader/follower relationship of asymmetric control between the core and the satellites and give practical guidelines for robust colloidal SERS sensing probes.
- 403Jubb, A. M.; Allen, H. C. Vibrational Spectroscopic Characterization of Hematite, Maghemite, and Magnetite Thin Films Produced by Vapor Deposition. ACS Appl. Mater. Interfaces 2010, 2, 2804– 2812, DOI: 10.1021/am1004943Google Scholar403Vibrational Spectroscopic Characterization of Hematite, Maghemite, and Magnetite Thin Films Produced by Vapor DepositionJubb, Aaron M.; Allen, Heather C.ACS Applied Materials & Interfaces (2010), 2 (10), 2804-2812CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Thin films of three iron oxide polymorphs, hematite, maghemite, and magnetite, were produced on KBr substrates using a conventional electron beam deposition technique coupled with thermal annealing. This method allowed for iron oxide thin films free from chem. precursor contaminants. The films were characterized using FTIR spectroscopy, Raman microspectroscopy, and ellipsometry. These spectroscopic techniques allowed for a clear assignment of the phase of the iron oxide polymorph films produced along with an examn. of the degree of crystallinity possessed by the films. The films produced were uniform in phase and exhibited decreasing crystallinity as the thickness increased from 40 to 250 nm.
- 404Nguyen, L. H. B.; Olchowka, J.; Belin, S.; Sanz Camacho, P.; Duttine, M.; Iadecola, A.; Fauth, F.; Carlier, D.; Masquelier, C.; Croguennec, L. Monitoring the Crystal Structure and the Electrochemical Properties of Na3(VO)2(PO4)2F through Fe3+ Substitution. ACS Appl. Mater. Interfaces 2019, 11, 38808– 38818, DOI: 10.1021/acsami.9b14249Google Scholar404Monitoring the Crystal Structure and the Electrochemical Properties of Na3(VO)2(PO4)2F through Fe3+ SubstitutionNguyen, Long H. B.; Olchowka, Jacob; Belin, Stephanie; Sanz Camacho, Paula; Duttine, Mathieu; Iadecola, Antonella; Fauth, Francois; Carlier, Dany; Masquelier, Christian; Croguennec, LaurenceACS Applied Materials & Interfaces (2019), 11 (42), 38808-38818CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)We here present the synthesis of a new material, Na3(VO)Fe(PO4)2F2, by the sol-gel method. Its at. and electronic structural descriptions are detd. by a combination of several diffraction and spectroscopy techniques such as synchrotron X-ray powder diffraction and synchrotron X-ray absorption spectroscopy at V and Fe K edges, 57Fe Mossbauer, and 31P solid-state NMR spectroscopy. The crystal structure of this newly obtained phase is similar to that of Na3(VO)2(PO4)2F, with a random distribution of Fe3+ ions over vanadium sites. Even though Fe3+ and V4+ ions situate on the same crystallog. position, their local environment can be studied sep. using 57Fe Mossbauer and X-ray absorption spectroscopy at Fe and V K edges, resp. The Fe3+ ion resides in a sym. octahedral environment, while the octahedral site of V4+ is greatly distorted due to the presence of the vanadyl bond. No electrochem. activity of the Fe4+/Fe3+ redox couple is detected, at least up to 5 V, whereas the redn. of Fe3+ to Fe2+ has been obsd. at ∼1.5 V vs. Na+/Na through the insertion of 0.5 Na+ into Na3(VO)Fe(PO4)2F2. Comparing to Na3(VO)2(PO4)2F, the electrochem. profile of Na3(VO)Fe(PO4)2F2 in the same cycling condition shows a smaller polarization which could be due to a slight improvement in Na+ diffusion process thanks to the presence of Fe3+ in the framework. Furthermore, the desodiation mechanism occurring upon charging is investigated by operando synchrotron X-ray diffraction and operando synchrotron X-ray absorption at V K edge.
- 405Sanchez, S. R.; Bachilo, S. M.; Kadria-Vili, Y.; Lin, C. W.; Weisman, R. B. n,m)-Specific Absorption Cross Sections of Single-Walled Carbon Nanotubes Measured by Variance Spectroscopy. Nano Lett. 2016, 16, 6903– 6909, DOI: 10.1021/acs.nanolett.6b02819Google Scholar405(n,m)-Specific Absorption Cross Sections of Single-Walled Carbon Nanotubes Measured by Variance SpectroscopySanchez, Stephen R.; Bachilo, Sergei M.; Kadria-Vili, Yara; Lin, Ching-Wei; Weisman, R. BruceNano Letters (2016), 16 (11), 6903-6909CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)A new method based on variance spectroscopy has enabled the detn. of abs. absorption cross sections for the 1st electronic transition of 12 (n,m) structural species of semiconducting single-walled C nanotubes (SWCNTs). Spectrally resolved measurements of fluorescence variance in dil. bulk samples provided particle no. concns. of specific SWCNT species. These values were converted to C concns. and correlated with resonant components in the absorbance spectrum to deduce (n,m)-specific absorption cross sections (absorptivities) for nanotubes ranging in diam. from 0.69 to 1.03 nm. The measured cross sections per atom tend to vary inversely with nanotube diam. and are slightly greater for structures of mod 1 type than for mod 2. Directly measured and extrapolated values are now available to support quant. anal. of SWCNT samples through absorption spectroscopy.
- 406Lee, H. K.; Lee, Y. H.; Zhang, Q.; Phang, I. Y.; Tan, J. M. R.; Cui, Y.; Ling, X. Y. Superhydrophobic Surface-Enhanced Raman Scattering Platform Fabricated by Assembly of Ag Nanocubes for Trace Molecular Sensing. ACS Appl. Mater. Interfaces 2013, 5, 11409– 11418, DOI: 10.1021/am403655gGoogle Scholar406Superhydrophobic Surface-Enhanced Raman Scattering Platform Fabricated by Assembly of Ag Nanocubes for Trace Molecular SensingLee, Hiang Kwee; Lee, Yih Hong; Zhang, Qi; Phang, In Yee; Tan, Joel Ming Rui; Cui, Yan; Ling, Xing YiACS Applied Materials & Interfaces (2013), 5 (21), 11409-11418CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)An anal. platform suitable for trace detection using a small vol. of analyte is pertinent to the field of toxin detection and criminol. Plasmonic nanostructures provide surface-enhanced Raman scattering (SERS) that can potentially achieve trace toxins and/or mols. detection. However, the detection of highly dild., small vol. samples remains a challenge. Here, the authors fabricate a superhydrophobic SERS platform by assembling Ag nanocubes that support strong surface plasmon and chem. functionalization for trace detection with sample vol. of just 1 μL. The authors' strategy integrates the intense electromagnetic field confinement generated by Ag nanocubes with a superhydrophobic surface capable of analyte concn. to lower the mol. detection limit. Single cryst. Ag nanocubes are assembled using the Langmuir-Blodgett technique to create surface roughness. To create a stable superhydrophobic SERS platform, an addnl. 25 nm Ag coating is evapd. over the Ag nanocubes to 'weld' the Ag nanocubes onto the substrate followed by chem. functionalization with perfluorodecanethiol. The resulting substrate has an advancing contact angle of 169° ± 5°. The authors' superhydrophobic platform confines analyte mols. within a small area and prevents the random spreading of mols. An analyte concg. factor of 14-fold is attained, as compared to a hydrophilic surface. Consequently, the detection limit of the authors' superhydrophobic SERS substrate reaches 10-16 M (100 aM) for rhodamine 6G using 1 μL analyte solns. An anal. SERS enhancement factor of 1011 is achieved. The authors' protocol is a general method that provides a simple, cost-effective approach to develop a stable and uniform superhydrophobic SERS platform for trace mol. sensing.
- 407Hahm, E.; Cha, M. G.; Kang, E. J.; Pham, X. H.; Lee, S. H.; Kim, H. M.; Kim, D. E.; Lee, Y. S.; Jeong, D. H.; Jun, B. H. Multilayer Ag-Embedded Silica Nanostructure as a Surface-Enhanced Raman Scattering-Based Chemical Sensor with Dual-Function Internal Standards. ACS Appl. Mater. Interfaces 2018, 10, 40748– 40755, DOI: 10.1021/acsami.8b12640Google Scholar407Multilayer Ag-Embedded Silica Nanostructure as a Surface-Enhanced Raman Scattering-Based Chemical Sensor with Dual-Function Internal StandardsHahm, Eunil; Cha, Myeong Geun; Kang, Eun Ji; Pham, Xuan-Hung; Lee, Sang Hun; Kim, Hyung-Mo; Kim, Dong-Eun; Lee, Yoon-Sik; Jeong, Dae-Hong; Jun, Bong-HyunACS Applied Materials & Interfaces (2018), 10 (47), 40748-40755CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Surface-enhanced Raman scattering (SERS) spectroscopy is attractive in various detection anal. fields. However, the quant. method using SERS spectroscopy remains as an area to be developed. The key issues in developing quant. anal. methods by using SERS spectroscopy are the fabrication of reliable SERS-active materials such as nanoparticle-based structures and the acquisition of the SERS signal without any disturbance that may change the SERS signal intensity and frequency. Here, the fabrication of seamless multilayered core-shell nanoparticles with an embedded Raman label compd. as an internal std. (MLRLC dots) for quant. SERS anal. is reported. The embedded Raman label compd. in the nanostructure provides a ref. value for calibrating the SERS signals. By using the MLRLC dots, it is possible to gain target analyte signals of different concns. while retaining the Raman signal of the internal std. The ML4-BBT dots, contg. 4-bromobenzenethiol (4-BBT) as an internal std., are successfully applied in the quant. anal. of 4-fluorobenzenethiol and thiram, a model pesticide. Addnl., ratiometric anal. was proved practical through normalization of the relative SERS intensity. The ratiometric strategy could be applied to various SERS substrates for quant. detection of a wide variety of targets.
- 408Feng, H.; Fu, Q.; Du, W.; Zhu, R.; Ge, X.; Wang, C.; Li, Q.; Su, L.; Yang, H.; Song, J. Quantitative Assessment of Copper(II) in Wilson’s Disease Based on Photoacoustic Imaging and Ratiometric Surface-Enhanced Raman Scattering. ACS Nano 2021, 15, 3402– 3414, DOI: 10.1021/acsnano.0c10407Google Scholar408Quantitative Assessment of Copper(II) in Wilson's Disease Based on Photoacoustic Imaging and Ratiometric Surface-Enhanced Raman ScatteringFeng, Hongjuan; Fu, Qinrui; Du, Wei; Zhu, Rong; Ge, Xiaoguang; Wang, Chenlu; Li, Qingqing; Su, Lichao; Yang, Huanghao; Song, JibinACS Nano (2021), 15 (2), 3402-3414CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Cu2+ is closely related to the occurrence and development of Wilson's disease (WD), and quant. detection of various copper indicators (esp. liver Cu2 and urinary Cu2+) is the key step for the early diagnosis of WD in the clinic. However, the clinic Cu2+ detection approach was mainly based on testing the liver tissue through combined invasive liver biopsy and the ICP-MS method, which is painful for the patient and limited in detg. WD status in real-time. Herein, we rationally designed a type of Cu2+-activated nanoprobe based on nanogapped gold nanoparticles (AuNNP) and poly(N-isopropylacrylamide) (PNIPAM) to simultaneously quantify the liver Cu2+ content and urinary Cu2+ in WD by photoacoustic (PA) imaging and ratiometric surface-enhanced Raman scattering (SERS), resp. In the nanoprobe, one Raman mol. of 2-naphthylthiol (NAT) was placed in the nanogap of AuNNP. PNIPAM and the other Raman mol. mercaptobenzonitrile (MBN) were coated on the AuNNP surface, named AuNNP-NAT@MBN/PNIPAM. Cu2+ can efficiently coordinate with the chelator PNIPAM and lead to aggregation of the nanoprobe, resulting in the absorption red-shift and increased PA performance of the nanoprobe in the NIR-II window. Meanwhile, the SERS signal at 2223 cm-1 of MBN is amplified, while the SERS signal at 1378 cm-1 of NAT remains stable, generating a ratiometric SERS I2223/I1378 signal. Both NIR-II PA1250 nm and SERS I2223/I1378 signals of the nanoprobe show a linear relationship with the concn. of Cu2+. The nanoprobe was successfully applied for in vivo quant. detection of liver Cu2+ of WD mice through NIR-II PA imaging and accurate quantification of urinary Cu2+ of WD patients by ratiometric SERS. We anticipate that the activatable nanoprobe might be applied for assisting an early, precise diagnosis of WD in the clinic in the future.
- 409Subaihi, A.; Muhamadali, H.; Mutter, S. T.; Blanch, E.; Ellis, D. I.; Goodacre, R. Quantitative detection of codeine in human plasma using surface-enhanced Raman scattering via adaptation of the isotopic labelling principle. Analyst 2017, 142, 1099– 1105, DOI: 10.1039/C7AN00193BGoogle ScholarThere is no corresponding record for this reference.
- 410Fu, X.; Lou, T.; Chen, Z.; Lin, M.; Feng, W.; Chen, L. ″Turn-on″ fluorescence detection of lead ions based on accelerated leaching of gold nanoparticles on the surface of graphene. ACS Appl. Mater. Interfaces 2012, 4, 1080– 1086, DOI: 10.1021/am201711jGoogle Scholar410"Turn-on" Fluorescence Detection of Lead Ions Based on Accelerated Leaching of Gold Nanoparticles on the Surface of GrapheneFu, Xiuli; Lou, Tingting; Chen, Zhaopeng; Lin, Meng; Feng, Weiwei; Chen, LingxinACS Applied Materials & Interfaces (2012), 4 (2), 1080-1086CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)A novel platform for effective turn-on fluorescence sensing of lead ions (Pb2+) in aq. soln. was developed based on gold nanoparticle (AuNP)-functionalized graphene. The AuNP-functionalized graphene exhibited minimal background fluorescence because of the extraordinarily high quenching ability of AuNPs. The AuNP-functionalized graphene underwent fluorescence restoration as well as significant enhancement upon adding Pb2+, which was attributed to the fact that Pb2+ could accelerate the leaching rate of the AuNPs on graphene surfaces in the presence of both thiosulfate (S2O32-) and 2-mercaptoethanol (2-ME). Consequently, this could be used as the basis for selective detection of Pb2+. With the optimum conditions chosen, the relative fluorescence intensity showed good linearity vs. logarithm concn. of Pb2+ at 50-1000 nM (R = 0.9982), and a detection limit of 10 nM. High selectivity over common coexistent metal ions was also demonstrated. The practical application had been carried out for detn. of Pb2+ in tap water and mineral water samples. The Pb2+-specific turn-on fluorescence sensor, based on Pb2+ accelerated leaching of AuNPs on the surface of graphene, provided new opportunities for highly sensitive and selective Pb2+ detection in aq. media.
- 411Ci, Q.; Liu, J.; Qin, X.; Han, L.; Li, H.; Yu, H.; Lim, K. L.; Zhang, C. W.; Li, L.; Huang, W. Polydopamine Dots-Based Fluorescent Nanoswitch Assay for Reversible Recognition of Glutamic Acid and Al3+ in Human Serum and Living Cell. ACS Appl. Mater. Interfaces 2018, 10, 35760– 35769, DOI: 10.1021/acsami.8b12087Google Scholar411Polydopamine Dots-Based Fluorescent Nanoswitch Assay for Reversible Recognition of Glutamic Acid and Al3+ in Human Serum and Living CellCi, Qiaoqiao; Liu, Jinhua; Qin, Xiaofei; Han, Linqi; Li, Hai; Yu, Haidong; Lim, Kah-Leong; Zhang, Cheng-Wu; Li, Lin; Huang, WeiACS Applied Materials & Interfaces (2018), 10 (42), 35760-35769CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)We developed a facile and feasible fluorescent nanoswitch assay for reversible recognition of glutamate (Glu) and Al3+ in human serum and living cell. The proposed nanoswitch assay is based on our recently developed method for controlled synthesis of fluorescent polydopamine dots (PDADs) at room temp. with dopamine as the sole precursor. The fluorescence of nanoswitch assay could be quickly and efficiently quenched by Glu (turn-Off), and the addn. of Al3+ could recover the fluorescence of the PDADs-Glu system (turn-On). Meanwhile, the reversible recognition of Glu and Al3+ in this nanoswitch system was stable after three cycles. Addnl., the system displayed excellent performance for Glu and Al3+ detn. with a low detection limit of 0.12 and 0.2 μM, resp. Moreover, PDADs are successfully applied to det. Glu and monitor Al3+ in human serum. Noteworthy, the nanoswitch assay is transported into HepG2 cells and realized "Off" detection of Glu and "On" sensing Al3+ in the living cells. Therefore, this PDADs-based nanoswitch assay provides a strategy to develop reversible recognition biosensors for intracellular and external mol. anal.
- 412Hidi, I. J.; Jahn, M.; Weber, K.; Bocklitz, T.; Pletz, M. W.; Cialla-May, D.; Popp, J. Lab-on-a-Chip-Surface Enhanced Raman Scattering Combined with the Standard Addition Method: Toward the Quantification of Nitroxoline in Spiked Human Urine Samples. Anal. Chem. 2016, 88, 9173– 9180, DOI: 10.1021/acs.analchem.6b02316Google Scholar412Lab-on-a-Chip-Surface Enhanced Raman Scattering Combined with the Standard Addition Method: Toward the Quantification of Nitroxoline in Spiked Human Urine SamplesHidi, Izabella J.; Jahn, Martin; Weber, Karina; Bocklitz, Thomas; Pletz, Mathias W.; Cialla-May, Dana; Popp, JuergenAnalytical Chemistry (Washington, DC, United States) (2016), 88 (18), 9173-9180CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)The emergence of antibacterial resistance and the development of new drugs lead to a continuous change of guidelines for medical treatments. Hence, new anal. tools are required for the detection of drugs in biol. fluids. In this study, the first surface enhanced Raman scattering (SERS) detection of nitroxoline (NTX) in purified water and in spiked human urine samples is reported. Insights concerning the nature of the mol.-metal interaction and its influence on the overall SERS signal are provided. Furthermore, three randomly collected urine samples originating from a healthy volunteer were spiked to assess the limit of detection (LOD), the limit of quantification (LOQ), and the linear dynamic range of the lab-on-a-chip SERS (LoC-SERS) method for NTX detection in human urine. The LOD is ∼3 μM (0.57 mg/L), LOQ ∼ 6.5 μM (1.23 mg/L) while the linear range is between 4.28 and 42.8 μM (0.81-8.13 mg/L). This covers the min. inhibitory concn. (MIC) values of the most commonly encountered uropathogens. Finally, seven clin. samples having an "unknown" NTX concn. were simulated. The LoC-SERS technique combined with the std. addn. method and statistical data anal. provided a good prediction of the unknown concns. Addnl., it is also demonstrated that the predictions carried out by multicurve resoln. alternating least-squares (MCR-ALS) algorithm provides reliable results, and it is preferred to a univariate statistical approach.
- 413Qing, G.; Lu, Q.; Li, X.; Liu, J.; Ye, M.; Liang, X.; Sun, T. Hydrogen bond based smart polymer for highly selective and tunable capture of multiply phosphorylated peptides. Nat. Commun. 2017, 8, 461, DOI: 10.1038/s41467-017-00464-0Google Scholar413Hydrogen bond based smart polymer for highly selective and tunable capture of multiply phosphorylated peptidesQing Guangyan; Lu Qi; Sun Taolei; Li Xiuling; Liu Jing; Ye Mingliang; Liang Xinmiao; Sun TaoleiNature communications (2017), 8 (1), 461 ISSN:.Multisite phosphorylation is an important and common mechanism for finely regulating protein functions and subsequent cellular responses. However, this study is largely restricted by the difficulty to capture low-abundance multiply phosphorylated peptides (MPPs) from complex biosamples owing to the limitation of enrichment materials and their interactions with phosphates. Here we show that smart polymer can serve as an ideal platform to resolve this challenge. Driven by specific but tunable hydrogen bonding interactions, the smart polymer displays differential complexation with MPPs, singly phosphorylated and non-modified peptides. Importantly, MPP binding can be modulated conveniently and precisely by solution conditions, resulting in highly controllable MPP adsorption on material surface. This facilitates excellent performance in MPP enrichment and separation from model proteins and real biosamples. High enrichment selectivity and coverage, extraordinary adsorption capacities and recovery towards MPPs, as well as high discovery rates of unique phosphorylation sites, suggest its great potential in phosphoproteomics studies.Capture of low-abundance multiply phosphorylated peptides (MPPs) is difficult due to limitation of enrichment materials and their interactions with phosphates. Here the authors show, a smart polymer driven by specific but tunable hydrogen bonding interactions can differentially complex with MPPs, singly phosphorylated and non-modified peptides.
- 414Jordan, M. I.; Mitchell, T. M. Machine learning: Trends, perspectives, and prospects. Science 2015, 349, 255– 260, DOI: 10.1126/science.aaa8415Google Scholar414Machine learning: Trends, perspectives, and prospectsJordan, M. I.; Mitchell, T. M.Science (Washington, DC, United States) (2015), 349 (6245), 255-260CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)Machine learning addresses the question of how to build computers that improve automatically through experience. It is one of today's most rapidly growing tech. fields, lying at the intersection of computer science and statistics, and at the core of artificial intelligence and data science. Recent progress in machine learning has been driven both by the development of new learning algorithms and theory and by the ongoing explosion in the availability of online data and low-cost computation. The adoption of data-intensive machine-learning methods can be found throughout science, technol. and commerce, leading to more evidence-based decision-making across many walks of life, including health care, manufg., education, financial modeling, policing, and marketing.
- 415Leong, Y. X.; Tan, E. X.; Leong, S. X.; Lin Koh, C. S.; Thanh Nguyen, L. B.; Ting Chen, J. R.; Xia, K.; Ling, X. Y. Where Nanosensors Meet Machine Learning: Prospects and Challenges in Detecting Disease X. ACS Nano 2022, 16, 13279– 13293, DOI: 10.1021/acsnano.2c05731Google Scholar415Where Nanosensors Meet Machine Learning: Prospects and Challenges in Detecting Disease XLeong, Yong Xiang; Tan, Emily Xi; Leong, Shi Xuan; Lin Koh, Charlynn Sher; Thanh Nguyen, Lam Bang; Ting Chen, Jaslyn Ru; Xia, Kelin; Ling, Xing YiACS Nano (2022), 16 (9), 13279-13293CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Disease X is a hypothetical unknown disease that has the potential to cause an epidemic or pandemic outbreak in the future. Nanosensors are attractive portable devices that can swiftly screen disease biomarkers on site, reducing the reliance on lab.-based analyses. However, conventional data analytics limit the progress of nanosensor research. In this Perspective, we highlight the integral role of machine learning (ML) algorithms in advancing nanosensing strategies toward Disease X detection. We first summarize recent progress in utilizing ML algorithms for the smart design and fabrication of custom nanosensor platforms as well as realizing rapid on-site prediction of infection statuses. Subsequently, we discuss promising prospects in further harnessing the potential of ML algorithms in other aspects of nanosensor development and biomarker detection.
- 416Chen, A.; Wang, Z.; Zhang, X.; Chen, L.; Hu, X.; Han, Y.; Cai, J.; Zhou, Z.; Li, J. Accelerated Mining of 2D Van der Waals Heterojunctions by Integrating Supervised and Unsupervised Learning. Chem. Mater. 2022, 34, 5571– 5583, DOI: 10.1021/acs.chemmater.2c00641Google Scholar416Accelerated Mining of 2D Van der Waals Heterojunctions by Integrating Supervised and Unsupervised LearningChen, An; Wang, Zhilong; Zhang, Xu; Chen, Letian; Hu, Xu; Han, Yanqiang; Cai, Junfei; Zhou, Zhen; Li, JinjinChemistry of Materials (2022), 34 (12), 5571-5583CODEN: CMATEX; ISSN:0897-4756. (American Chemical Society)The contact resistance of the metal-semiconductor interface at the source and drain increases as the injection of carriers decreases, degrading the device performance. Reducing the Schottky barrier height (SBH) at the metal-semiconductor interface is an effective way of reducing the contact resistance. Therefore, exploring Ohmic contact (no Schottky barrier) or low contact resistance two-dimensional (2D) semiconductor/metal heterojunctions is crit. for developing high-performance electronic devices. We generate a comprehensive dataset from the periodic table consisting of 1092 potential 2D semiconductor/metal heterojunctions with good contact performances and demonstrate that the small interfacial dipole and the elimination of localized surface states are essential for designing advanced 2D metal-semiconductor systems with small SBHs. We use integrated supervised and unsupervised learning, as well as first-principles calcns., to screen 6 potential 2D van der Waals metal-semiconductor heterojunctions (BTe-NbSe2, Al2SO-Zn3C2, iAl2SO-Zn3C2, GaSe-NbS2, GaSe-NbSe2, and GeSe-VS2) with Ohmic contact and high tunneling probabilities from 1092 candidates. The proposed method takes less than 5 s to execute and is far superior to traditional first-principles calcns. in both time and cost, demonstrating the superiority of using machine learning for screening materials and that unsupervised assisted algorithm can alleviate the problem of data scarcity to predict the behaviors of complex dynamical systems.
- 417Anker, A. S.; Butler, K. T.; Selvan, R.; Jensen, K. M. Ø. Machine learning for analysis of experimental scattering and spectroscopy data in materials chemistry. Chemical Science 2023, 14, 14003– 14019, DOI: 10.1039/D3SC05081EGoogle ScholarThere is no corresponding record for this reference.
- 418Glielmo, A.; Husic, B. E.; Rodriguez, A.; Clementi, C.; Noé, F.; Laio, A. Unsupervised Learning Methods for Molecular Simulation Data. Chem. Rev. 2021, 121, 9722– 9758, DOI: 10.1021/acs.chemrev.0c01195Google Scholar418Unsupervised Learning Methods for Molecular Simulation DataGlielmo, Aldo; Husic, Brooke E.; Rodriguez, Alex; Clementi, Cecilia; Noe, Frank; Laio, AlessandroChemical Reviews (Washington, DC, United States) (2021), 121 (16), 9722-9758CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review. Unsupervised learning is becoming an essential tool to analyze the increasingly large amts. of data produced by atomistic and mol. simulations, in material science, solid state physics, biophysics, and biochem. In this Review, we provide a comprehensive overview of the methods of unsupervised learning that have been most commonly used to investigate simulation data and indicate likely directions for further developments in the field. In particular, we discuss feature representation of mol. systems and present state-of-the-art algorithms of dimensionality redn., d. estn., and clustering, and kinetic models. We divide our discussion into self-contained sections, each discussing a specific method. In each section, we briefly touch upon the math. and algorithmic foundations of the method, highlight its strengths and limitations, and describe the specific ways in which it has been used-or can be used-to analyze mol. simulation data.
- 419Yuan, Y.; Ren, J.; Xue, H.; Li, J.; Tang, F.; La, P.; Lu, X. Insight into the Electronic Properties of Semiconductor Heterostructure Based on Machine Learning and First-Principles. ACS Appl. Mater. Interfaces 2023, 15, 12462– 12472, DOI: 10.1021/acsami.2c15957Google ScholarThere is no corresponding record for this reference.
- 420Willhelm, D.; Wilson, N.; Arroyave, R.; Qian, X.; Cagin, T.; Pachter, R.; Qian, X. Predicting Van der Waals Heterostructures by a Combined Machine Learning and Density Functional Theory Approach. ACS Appl. Mater. Interfaces 2022, 14, 25907– 25919, DOI: 10.1021/acsami.2c04403Google ScholarThere is no corresponding record for this reference.
- 421Singh, A. V.; Maharjan, R. S.; Kanase, A.; Siewert, K.; Rosenkranz, D.; Singh, R.; Laux, P.; Luch, A. Machine-Learning-Based Approach to Decode the Influence of Nanomaterial Properties on Their Interaction with Cells. ACS Appl. Mater. Interfaces 2021, 13, 1943– 1955, DOI: 10.1021/acsami.0c18470Google Scholar421Machine-Learning-Based Approach to Decode the Influence of Nanomaterial Properties on Their Interaction with CellsSingh, Ajay Vikram; Maharjan, Romi-Singh; Kanase, Anurag; Siewert, Katherina; Rosenkranz, Daniel; Singh, Rishabh; Laux, Peter; Luch, AndreasACS Applied Materials & Interfaces (2021), 13 (1), 1943-1955CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)In an in vitro nanotoxicity system, cell-nanoparticle (NP) interaction leads to the surface adsorption, uptake, and changes into nuclei/cell phenotype and chem., as an indicator of oxidative stress, genotoxicity, and carcinogenicity. Different types of nanomaterials and their chem. compn. or "corona" have been widely studied in context with nanotoxicol. However, rare reports are available, which delineate the details of the cell shape index (CSI) and nuclear area factors (NAFs) as a descriptor of the type of nanomaterials. In this paper, we propose a machine-learning-based graph modeling and correlation-establishing approach using tight junction protein ZO-1-mediated alteration in the cell/nuclei phenotype to quantify and propose it as indexes of cell-NP interactions. We believe that the phenotypic variation (CSI and NAF) in the epithelial cell is governed by the physicochem. descriptors (e.g., shape, size, zeta potential, concn., diffusion coeffs., polydispersity, and so on) of the different classes of nanomaterials, which critically dets. the intracellular uptake or cell membrane interactions when exposed to the epithelial cells at sub-lethal concns. The intrinsic and extrinsic physicochem. properties of the representative nanomaterials (NMs) were measured using optical (dynamic light scattering, NP tracking anal.) methods to create a set of nanodescriptors contributing to cell-NM interactions via phenotype adjustments. We used correlation function as a machine-learning algorithm to successfully predict cell and nuclei shapes and polarity functions as phenotypic markers for five different classes of nanomaterials studied herein this report. The CSI and NAF as nanodescriptors can be used as intuitive cell phenotypic parameters to define the safety of nanomaterials extensively used in consumer products and nanomedicine.
- 422Pan, Z.; Zhou, Y.; Zhang, L. Photoelectrochemical Properties, Machine Learning, and Symbolic Regression for Molecularly Engineered Halide Perovskite Materials in Water. ACS Appl. Mater. Interfaces 2022, 14, 9933– 9943, DOI: 10.1021/acsami.2c00568Google Scholar422Photoelectrochemical Properties, Machine Learning, and Symbolic Regression for Molecularly Engineered Halide Perovskite Materials in WaterPan, Zheng; Zhou, Yinguo; Zhang, LeiACS Applied Materials & Interfaces (2022), 14 (7), 9933-9943CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)The machine learning techniques are capable of predicting virtual material design space and optimizing material fabrication parameters. In this article, we construct machine learning models to describe the photoelectrochem. properties of molecularly engineered halide perovskite materials based on CH3NH3PbI3 in an aq. soln. and predict a complex multidimensional design space for the halide perovskite materials. The machine learning models are trained and tested based on an exptl. photocurrent data set consisting of 360 data points with varying exptl. conditions and dye structures. Machine learning algorithms including support vector machine (SVM), random forest, k-nearest neighbors, Rpart, Xgboost, and Kriging algorithms are compared, with the Kriging algorithm achieving the best accuracies (r = 0.99 and R2 = 0.98) and SVM achieving the second best. A total of 50,905 data points representing the complex multidimensional design space are predicted via the machine-learned models to benefit the future perovskite studies. In addn., the symbolic regression based on the genetic algorithms effectively and automatically designs hybrid descriptors that outperform the individual descriptors. This article highlights the machine learning and symbolic regression methods for designing stable and high-performance halide perovskite materials and serves as a platform for further exptl. optimization of halide perovskite materials.
- 423Shin, H.; Jeong, H.; Park, J.; Hong, S.; Choi, Y. Correlation between Cancerous Exosomes and Protein Markers Based on Surface-Enhanced Raman Spectroscopy (SERS) and Principal Component Analysis (PCA). ACS Sensors 2018, 3, 2637– 2643, DOI: 10.1021/acssensors.8b01047Google Scholar423Correlation between Cancerous Exosomes and Protein Markers Based on Surface-Enhanced Raman Spectroscopy (SERS) and Principal Component Analysis (PCA)Shin, Hyunku; Jeong, Hyesun; Park, Jaena; Hong, Sunghoi; Choi, YeonhoACS Sensors (2018), 3 (12), 2637-2643CODEN: ASCEFJ; ISSN:2379-3694. (American Chemical Society)Exosomes, which are nanovesicles secreted by cells, are promising biomarkers for cancer diagnosis and prognosis, based on their sp. surface protein compns. Here, we demonstrate the correlation of nonsmall cell lung cancer (NSCLC) cell-derived exosomes and potential protein markers by unique Raman scattering profiles and principal component anal. (PCA) for cancer diagnosis. On the basis of surface enhanced Raman scattering (SERS) signals of exosomes from normal and NSCLC cells, we extd. Raman patterns of cancerous exosomes by PCA and clarified specific patterns as unique peaks through quant. anal. with ratiometric mixts. of cancerous and normal exosomes. The unique peaks correlated well with cancerous exosome ratio (R2 > 90%) as the unique Raman band of NSCLC exosome. To examine the origin of the unique peaks, we compared these unique peaks with characteristic Raman bands of several exosomal protein markers (CD9, CD81, EpCAM, and EGFR). EGFR had 1.97-fold similarity in Raman profiles than other markers, and it showed dominant expression against the cancerous exosomes in an immunoblotting result. We expect that these results will contribute to studies on exosomal surface protein markers for diagnosis of cancers.
- 424Ding, Z.; Wang, C.; Song, X.; Li, N.; Zheng, X.; Wang, C.; Su, M.; Liu, H. Strong π-Metal Interaction Enables Liquid Interfacial Nanoarray–Molecule Co-assembly for Raman Sensing of Ultratrace Fentanyl Doped in Heroin, Ketamine, Morphine, and Real Urine. ACS Appl. Mater. Interfaces 2023, 15, 12570– 12579, DOI: 10.1021/acsami.2c22607Google Scholar424Strong π-Metal Interaction Enables Liquid Interfacial Nanoarray-Molecule Co-assembly for Raman Sensing of Ultratrace Fentanyl Doped in Heroin, Ketamine, Morphine, and Real UrineDing, Zhongxiang; Wang, Chao; Song, Xin; Li, Ning; Zheng, Xinyong; Wang, Chenxue; Su, Mengke; Liu, HonglinACS Applied Materials & Interfaces (2023), 15 (9), 12570-12579CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Toward the challenge on reliable detn. of trace fentanyl to avoid opioid overdose death in drug crisis, here we realize rapid and direct detection of trace fentanyl in real human urine without pretreatment by a portable surface enhanced Raman spectroscopy (SERS) strategy on liq./liq. interfacial (LLI) plasmonic arrays. It was obsd. that fentanyl could interact with the gold nanoparticles (GNPs) surface, facilitate the LLI self-assembly, and consequently amplify the detection sensitivity with a limit of detection (LOD) as low as 1 ng/mL in aq. soln. and 50 ng/mL spiked in urine. Furthermore, we achieve multiplex blind sample recognition and classification of ultratrace fentanyl doped in other illegal drugs, which has extremely low LODs at mass concns. of 0.02% (2 ng in 10μg of heroin), 0.02% (2 ng in 10μg of ketamine), and 0.1% (10 ng in 10μg of morphine). A logic circuit of the AND gate was constructed for automatic recognition of illegal drugs with or without fentanyl doping. The data-driven analog soft independent modeling model could quickly distinguish fentanyl-doped samples from illegal drugs with 100% specificity. Mol. dynamics (MD) simulation elucidates the underlying mol. mechanism of nanoarray-mol. co-assembly through strong π-metal interactions and the differences in the SERS signal of various drug mols. It paves a rapid identification, quantification, and classification strategy for trace fentanyl anal., indicating broad application prospects in response to the opioid epidemic crisis.
- 425Leong, Y. X.; Lee, Y. H.; Koh, C. S. L.; Phan-Quang, G. C.; Han, X.; Phang, I. Y.; Ling, X. Y. Surface-Enhanced Raman Scattering (SERS) Taster: A Machine-Learning-Driven Multireceptor Platform for Multiplex Profiling of Wine Flavors. Nano Lett. 2021, 21, 2642– 2649, DOI: 10.1021/acs.nanolett.1c00416Google Scholar425Surface-Enhanced Raman Scattering (SERS) Taster: A Machine-Learning-Driven Multireceptor Platform for Multiplex Profiling of Wine FlavorsLeong, Yong Xiang; Lee, Yih Hong; Koh, Charlynn Sher Lin; Phan-Quang, Gia Chuong; Han, Xuemei; Phang, In Yee; Ling, Xing YiNano Letters (2021), 21 (6), 2642-2649CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)Integrating machine learning with surface-enhanced Raman scattering (SERS) accelerates the development of practical sensing devices. Such integration, in combination with direct detection or indirect analyte capturing strategies, is key to achieving high predictive accuracies even in complex matrixes. However, in-depth understanding of spectral variations arising from specific chem. interactions is essential to prevent model overfit. Herein, we design a machine-learning-driven "SERS taster" to simultaneously harness useful vibrational information from multiple receptors for enhanced multiplex profiling of five wine flavor mols. at parts-per-million levels. Our receptors employ numerous noncovalent interactions to capture chem. functionalities within flavor mols. By strategically combining all receptor-flavor SERS spectra, we construct comprehensive "SERS superprofiles" for predictive analytics using chemometrics. We elucidate crucial mol.-level interactions in flavor identification and further demonstrate the differentiation of primary, secondary, and tertiary alc. functionalities. Our SERS taster also achieves perfect accuracies in multiplex flavor quantification in an artificial wine matrix.
- 426Nguyen, L. B. T.; Leong, Y. X.; Koh, C. S. L.; Leong, S. X.; Boong, S. K.; Sim, H. Y. F.; Phan-Quang, G. C.; Phang, I. Y.; Ling, X. Y. Inducing Ring Complexation for Efficient Capture and Detection of Small Gaseous Molecules Using SERS for Environmental Surveillance. Angew. Chem., Int. Ed. Engl. 2022, 61, e202207447, DOI: 10.1002/anie.202207447Google ScholarThere is no corresponding record for this reference.
- 427Lever, J.; Krzywinski, M.; Altman, N. Principal component analysis. Nat Methods 2017, 14, 641– 642, DOI: 10.1038/nmeth.4346Google Scholar427Points of Significance Principal component analysisLever, Jake; Krzywinski, Martin; Altman, NaomiNature Methods (2017), 14 (7), 641-642CODEN: NMAEA3; ISSN:1548-7091. (Nature Publishing Group)PCA helps you interpret your data, but it will not always find the important patterns.
- 428Nicholas, T. C.; Alexandrov, E. V.; Blatov, V. A.; Shevchenko, A. P.; Proserpio, D. M.; Goodwin, A. L.; Deringer, V. L. Visualization and Quantification of Geometric Diversity in Metal–Organic Frameworks. Chem. Mater. 2021, 33, 8289– 8300, DOI: 10.1021/acs.chemmater.1c02439Google Scholar428Visualization and Quantification of Geometric Diversity in Metal-Organic FrameworksNicholas, Thomas C.; Alexandrov, Eugeny V.; Blatov, Vladislav A.; Shevchenko, Alexander P.; Proserpio, Davide M.; Goodwin, Andrew L.; Deringer, Volker L.Chemistry of Materials (2021), 33 (21), 8289-8300CODEN: CMATEX; ISSN:0897-4756. (American Chemical Society)With ever-growing nos. of metal-org. framework (MOF) materials being reported, new computational approaches are required for a quant. understanding of structure-property correlations in MOFs. Here, we show how structural coarse-graining and embedding ("unsupervised learning") schemes can together give new insights into the geometric diversity of MOF structures. Based on a curated data set of 1262 reported exptl. structures, we automatically generate coarse-grained and rescaled representations which we couple to a kernel-based similarity metric and to widely used embedding schemes. This approach allows us to visualize the breadth of geometric diversity within individual topologies and to quantify the distributions of local and global similarities across the structural space of MOFs. The methodol. is implemented in an openly available Python package and is expected to be useful in future high-throughput studies.
- 429Sigle, M.; Rohlfing, A. K.; Kenny, M.; Scheuermann, S.; Sun, N.; Graeßner, U.; Haug, V.; Sudmann, J.; Seitz, C. M.; Heinzmann, D.; Schenke-Layland, K.; Maguire, P. B.; Walch, A.; Marzi, J.; Gawaz, M. P. Translating genomic tools to Raman spectroscopy analysis enables high-dimensional tissue characterization on molecular resolution. Nat. Commun. 2023, 14, 5799, DOI: 10.1038/s41467-023-41417-0Google ScholarThere is no corresponding record for this reference.
- 430Qu, J.; Xie, Y. R.; Ciesielski, K. M.; Porter, C. E.; Toberer, E. S.; Ertekin, E. Leveraging language representation for materials exploration and discovery. npj Computational Materials 2024, 10, 58, DOI: 10.1038/s41524-024-01231-8Google ScholarThere is no corresponding record for this reference.
- 431Martin, F. L.; Kelly, J. G.; Llabjani, V.; Martin-Hirsch, P. L.; Patel, I. I.; Trevisan, J.; Fullwood, N. J.; Walsh, M. J. Distinguishing cell types or populations based on the computational analysis of their infrared spectra. Nat. Protoc 2010, 5, 1748– 1760, DOI: 10.1038/nprot.2010.133Google Scholar431Distinguishing cell types or populations based on the computational analysis of their infrared spectraMartin, Francis L.; Kelly, Jemma G.; Llabjani, Valon; Martin-Hirsch, Pierre L.; Patel, Imran I.; Trevisan, Julio; Fullwood, Nigel J.; Walsh, Michael J.Nature Protocols (2010), 5 (11), 1748-1760CODEN: NPARDW; ISSN:1750-2799. (Nature Publishing Group)IR (IR) spectroscopy of intact cells results in a fingerprint of their biochem. in the form of an IR spectrum; this has given rise to the new field of biospectroscopy. This protocol describes sample prepn. (a tissue section or cytol. specimen), the application of IR spectroscopy tools, and computational anal. Exptl. considerations include optimization of specimen prepn., objective acquisition of a sufficient no. of spectra, linking of the derived spectra with tissue architecture or cell type, and computational anal. The prepn. of multiple specimens (up to 50) takes 8 h; the interrogation of a tissue section can take up to 6 h (∼100 spectra); and cytol. anal. (n = 50, 10 spectra per specimen) takes 14 h. IR spectroscopy generates complex data sets and analyses are best when initially based on a multivariate approach (principal component anal. with or without linear discriminant anal.). This results in the identification of class clustering as well as class-specific chem. entities.
- 432Leong, S. X.; Tan, E. X.; Han, X.; Luhung, I.; Aung, N. W.; Nguyen, L. B. T.; Tan, S. Y.; Li, H.; Phang, I. Y.; Schuster, S.; Ling, X. Y. Surface-Enhanced Raman Scattering-Based Surface Chemotaxonomy: Combining Bacteria Extracellular Matrices and Machine Learning for Rapid and Universal Species Identification. ACS Nano 2023, 17, 23132– 23143, DOI: 10.1021/acsnano.3c09101Google ScholarThere is no corresponding record for this reference.
- 433Del Villar-Guerra, R.; Trent, J. O.; Chaires, J. B. G-Quadruplex Secondary Structure Obtained from Circular Dichroism Spectroscopy. Angew. Chem., Int. Ed. Engl. 2018, 57, 7171– 7175, DOI: 10.1002/anie.201709184Google Scholar433G-Quadruplex Secondary Structure Obtained from Circular Dichroism SpectroscopyDel Villar-Guerra Rafael; Trent John O; Chaires Jonathan BAngewandte Chemie (International ed. in English) (2018), 57 (24), 7171-7175 ISSN:.A curated library of circular dichroism spectra of 23 G-quadruplexes of known structure was built and analyzed. The goal of this study was to use this reference library to develop an algorithm to derive quantitative estimates of the secondary structure content of quadruplexes from their experimental CD spectra. Principal component analysis and singular value decomposition were used to characterize the reference spectral library. CD spectra were successfully fit to obtain estimates of the amounts of base steps in anti-anti, syn-anti or anti-syn conformations, in diagonal or lateral loops, or in other conformations. The results show that CD spectra of nucleic acids can be analyzed to obtain quantitative structural information about secondary structure content in an analogous way to methods used to analyze protein CD spectra.
- 434Leong, S. X.; Koh, C. S. L.; Sim, H. Y. F.; Lee, Y. H.; Han, X.; Phan-Quang, G. C.; Ling, X. Y. Enantiospecific Molecular Fingerprinting Using Potential-Modulated Surface-Enhanced Raman Scattering to Achieve Label-Free Chiral Differentiation. ACS Nano 2021, 15, 1817– 1825, DOI: 10.1021/acsnano.0c09670Google Scholar434Enantiospecific Molecular Fingerprinting Using Potential-Modulated Surface-Enhanced Raman Scattering to Achieve Label-Free Chiral DifferentiationLeong, Shi Xuan; Koh, Charlynn Sher Lin; Sim, Howard Yi Fan; Lee, Yih Hong; Han, Xuemei; Phan-Quang, Gia Chuong; Ling, Xing YiACS Nano (2021), 15 (1), 1817-1825CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Chiral differentiation is crit. in diverse fields ranging from pharmaceutics to chiral synthesis. While surface-enhanced Raman scattering (SERS) offers mol.-specific vibrational information with high detection sensitivity, current strategies rely on indirect detection using addnl. selectors and cannot exploit SERS' key advantages for univocal and generic chiral differentiation. Here, we achieve direct, label-free SERS sensing of biol. important enantiomers by synergizing asym. nanoporous gold (NPG) nanoparticles with electrochem.-SERS to generate enantiospecific mol. fingerprints. Exptl. and in silico studies reveal that chiral recognition is two pronged. First, the numerous surface at. defects in NPG provide the necessary localized asym. environment to induce enantiospecific mol. adsorptions and interaction affinities. Concurrently, the applied potential drives and orients the enantiomers close to the NPG surface for maximal analyte-surface interactions. Notably, our strategy is versatile and can be readily extended to detect various enantiomers. Furthermore, we can achieve multiplex quantification of enantiomeric ratios with excellent predictive performance. Our combinatorial approach thus offers an important paradigm shift from current approaches to achieve label-free chiral SERS sensing of various enantiomers.
- 435Leong, S. X.; Leong, Y. X.; Tan, E. X.; Sim, H. Y. F.; Koh, C. S. L.; Lee, Y. H.; Chong, C.; Ng, L. S.; Chen, J. R. T.; Pang, D. W. C.; Nguyen, L. B. T.; Boong, S. K.; Han, X.; Kao, Y.-C.; Chua, Y. H.; Phan-Quang, G. C.; Phang, I. Y.; Lee, H. K.; Abdad, M. Y.; Tan, N. S.; Ling, X. Y. Noninvasive and Point-of-Care Surface-Enhanced Raman Scattering (SERS)-Based Breathalyzer for Mass Screening of Coronavirus Disease 2019 (COVID-19) under 5 min. ACS Nano 2022, 16, 2629– 2639, DOI: 10.1021/acsnano.1c09371Google Scholar435Noninvasive and Point-of-Care Surface-Enhanced Raman Scattering (SERS)-Based Breathalyzer for Mass Screening of Coronavirus Disease 2019 (COVID-19) under 5 minLeong, Shi Xuan; Leong, Yong Xiang; Tan, Emily Xi; Sim, Howard Yi Fan; Koh, Charlynn Sher Lin; Lee, Yih Hong; Chong, Carice; Ng, Li Shiuan; Chen, Jaslyn Ru Ting; Pang, Desmond Wei Cheng; Nguyen, Lam Bang Thanh; Boong, Siew Kheng; Han, Xuemei; Kao, Ya-Chuan; Chua, Yi Heng; Phan-Quang, Gia Chuong; Phang, In Yee; Lee, Hiang Kwee; Abdad, Mohammad Yazid; Tan, Nguan Soon; Ling, Xing YiACS Nano (2022), 16 (2), 2629-2639CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Population-wide surveillance of COVID-19 requires tests to be quick and accurate to minimize community transmissions. The detection of breath volatile org. compds. presents a promising option for COVID-19 surveillance but is currently limited by bulky instrumentation and inflexible anal. protocol. Here, we design a hand-held surface-enhanced Raman scattering-based breathalyzer to identify COVID-19 infected individuals in under 5 min, achieving >95% sensitivity and specificity across 501 participants regardless of their displayed symptoms. Our SERS-based breathalyzer harnesses key variations in vibrational fingerprints arising from interactions between breath metabolites and multiple mol. receptors to establish a robust partial least-squares discriminant anal. model for high throughput classifications. Crucially, spectral regions influencing classification show strong corroboration with reported potential COVID-19 breath biomarkers, both through expt. and in silico. Our strategy strives to spur the development of next-generation, noninvasive human breath diagnostic toolkits tailored for mass screening purposes.
- 436Kao, Y.-C.; Han, X.; Lee, Y. H.; Lee, H. K.; Phan-Quang, G. C.; Lay, C. L.; Sim, H. Y. F.; Phua, V. J. X.; Ng, L. S.; Ku, C. W.; Tan, T. C.; Phang, I. Y.; Tan, N. S.; Ling, X. Y. Multiplex Surface-Enhanced Raman Scattering Identification and Quantification of Urine Metabolites in Patient Samples within 30 min. ACS Nano 2020, 14, 2542– 2552, DOI: 10.1021/acsnano.0c00515Google Scholar436Multiplex Surface-Enhanced Raman Scattering Identification and Quantification of Urine Metabolites in Patient Samples within 30 minKao, Ya-Chuan; Han, Xuemei; Lee, Yih Hong; Lee, Hiang Kwee; Phan-Quang, Gia Chuong; Lay, Chee Leng; Sim, Howard Yi Fan; Phua, Vanessa Jing Xin; Ng, Li Shiuan; Ku, Chee Wai; Tan, Thiam Chye; Phang, In Yee; Tan, Nguan Soon; Ling, Xing YiACS Nano (2020), 14 (2), 2542-2552CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Successful translation of lab.-based surface-enhanced Raman scattering (SERS) platforms to clin. applications requires multiplex and ultratrace detection of small biomarker mols. from a complex biofluid. However, these biomarker mols. generally exhibit low Raman scattering cross sections and do not possess specific affinity to plasmonic nanoparticle surfaces, significantly increasing the challenge of detecting them at low concns. Herein, we demonstrate a "confine-and-capture" approach for multiplex detection of two families of urine metabolites correlated with miscarriage risks, 5β-pregnane-3α,20α-diol-3α-glucuronide and tetrahydrocortisone. To enhance SERS signals by 1012-fold, we use specific nanoscale surface chem. for targeted metabolite capture from a complex urine matrix prior to confining them on a superhydrophobic SERS platform. We then apply chemometrics, including principal component anal. and partial least-squares regression, to convert mol. fingerprint information into quantifiable readouts. The whole screening procedure requires only 30 min, including urine pretreatment, sample drying on the SERS platform, SERS measurements, and chemometric analyses. These readouts correlate well with the pregnancy outcomes in a case-control study of 40 patients presenting threatened miscarriage symptoms.
- 437Kim, W.; Lee, S. H.; Kim, J. H.; Ahn, Y. J.; Kim, Y. H.; Yu, J. S.; Choi, S. Paper-Based Surface-Enhanced Raman Spectroscopy for Diagnosing Prenatal Diseases in Women. ACS Nano 2018, 12, 7100– 7108, DOI: 10.1021/acsnano.8b02917Google Scholar437Paper-Based Surface-Enhanced Raman Spectroscopy for Diagnosing Prenatal Diseases in WomenKim, Wansun; Lee, Soo Hyun; Kim, Jin Hwi; Ahn, Yong Jin; Kim, Yeon-Hee; Yu, Jae Su; Choi, SamjinACS Nano (2018), 12 (7), 7100-7108CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)The authors report the development of a surface-enhanced Raman spectroscopy sensor chip by decorating gold nanoparticles (AuNPs) on ZnO nanorod (ZnO NR) arrays vertically grown on cellulose paper (C). These chips can enhance the Raman signal by 1.25 × 107 with an excellent reproducibility of <6%. The authors can measure trace amts. of human amniotic fluids of patients with subclin. intra-amniotic infection (IAI) and preterm delivery (PTD) using the chip in combination with a multivariate statistics-derived machine-learning-trained bioclassification method. The authors can detect the presence of prenatal diseases and identify the types of diseases from amniotic fluids with >92% clin. sensitivity and specificity. The authors' technol. has the potential to be used for the early detection of prenatal diseases and can be adapted for point-of-care applications.
- 438Torrisi, S. B.; Carbone, M. R.; Rohr, B. A.; Montoya, J. H.; Ha, Y.; Yano, J.; Suram, S. K.; Hung, L. Random forest machine learning models for interpretable X-ray absorption near-edge structure spectrum-property relationships. npj Computational Materials 2020, 6, 109, DOI: 10.1038/s41524-020-00376-6Google ScholarThere is no corresponding record for this reference.
- 439Chen, B.; Sheridan, R. P.; Hornak, V.; Voigt, J. H. Comparison of random forest and Pipeline Pilot Naïve Bayes in prospective QSAR predictions. J. Chem. Inf Model 2012, 52, 792– 803, DOI: 10.1021/ci200615hGoogle Scholar439Comparison of Random Forest and Pipeline Pilot Naive Bayes in Prospective QSAR PredictionsChen, Bin; Sheridan, Robert P.; Hornak, Viktor; Voigt, Johannes H.Journal of Chemical Information and Modeling (2012), 52 (3), 792-803CODEN: JCISD8; ISSN:1549-9596. (American Chemical Society)Random forest is currently considered one of the best QSAR methods available in terms of accuracy of prediction. However, it is computationally intensive. Naive Bayes is a simple, robust classification method. The Laplacian-modified Naive Bayes implementation is the preferred QSAR method in the widely used com. chemoinformatics platform Pipeline Pilot. We made a comparison of the ability of Pipeline Pilot Naive Bayes (PLPNB) and random forest to make accurate predictions on 18 large, diverse inhouse QSAR data sets. These include on-target and ADME-related activities. These data sets were set up as classification problems with either binary or multicategory activities. We used a time-split method of dividing training and test sets, as we feel this is a realistic way of simulating prospective prediction. PLPNB is computationally efficient. However, random forest predictions are at least as good and in many cases significantly better than those of PLPNB on our data sets. PLPNB performs better with ECFP4 and ECFP6 descriptors, which are native to Pipeline Pilot, and more poorly with other descriptors we tried.
- 440Sheridan, R. P.; Wang, W. M.; Liaw, A.; Ma, J.; Gifford, E. M. Extreme Gradient Boosting as a Method for Quantitative Structure-Activity Relationships. J. Chem. Inf Model 2016, 56, 2353– 2360, DOI: 10.1021/acs.jcim.6b00591Google Scholar440Extreme Gradient Boosting as a Method for Quantitative Structure-Activity RelationshipsSheridan, Robert P.; Wang, Wei Min; Liaw, Andy; Ma, Junshui; Gifford, Eric M.Journal of Chemical Information and Modeling (2016), 56 (12), 2353-2360CODEN: JCISD8; ISSN:1549-9596. (American Chemical Society)In the pharmaceutical industry it is common to generate many QSAR models from training sets contg. a large no. of mols. and a large no. of descriptors. The best QSAR methods are those that can generate the most accurate predictions but that are not overly expensive computationally. In this paper the authors compare extreme gradient boosting (XGBoost) to random forest and single-task deep neural nets on 30 inhouse data sets. While XGBoost has many adjustable parameters, the authors can define a set of std. parameters at which XGBoost makes predictions, on the av., better than those of random forest and almost as good as those of deep neural nets. The biggest strength of XGBoost is its speed. Whereas efficient use of random forest requires generating each tree in parallel on a cluster, and deep neural nets are usually run on GPUs, XGBoost can be run on a single cluster CPU in less than a third of the wall-clock time of either of the other methods.
- 441Schleder, G. R.; Acosta, C. M.; Fazzio, A. Exploring Two-Dimensional Materials Thermodynamic Stability via Machine Learning. ACS Appl. Mater. Interfaces 2020, 12, 20149– 20157, DOI: 10.1021/acsami.9b14530Google Scholar441Exploring Two-Dimensional Materials Thermodynamic Stability via Machine LearningSchleder, Gabriel R.; Acosta, Carlos Mera; Fazzio, AdalbertoACS Applied Materials & Interfaces (2020), 12 (18), 20149-20157CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)The increasing interest and research on two-dimensional (2D) materials has not yet translated into a reality of diverse materials applications. To go beyond graphene and transition metal dichalcogenides for several applications, suitable candidates with desirable properties must be proposed. Here we use machine learning techniques to identify thermodynamically stable 2D materials, which is the first essential requirement for any application. According to the formation energy and energy above the convex hull, we classify materials as having low, medium, or high stability. The proposed approach enables the stability evaluation of novel 2D compds. for further detailed investigation of promising candidates, using only compn. properties and structural symmetry, without the need for information about at. positions. We demonstrate the usefulness of the model generating more than a thousand novel compds., corroborating with DFT calcns. the classification for five of these materials. To illustrate the applicability of the stable materials, we then perform a screening of electronic materials suitable for photoelectrocatalytic water splitting, identifying the potential candidate Sn2SeTe generated by our model, and also PbTe, both not yet reported for this application.
- 442Ahmad, Z.; Xie, T.; Maheshwari, C.; Grossman, J. C.; Viswanathan, V. Machine Learning Enabled Computational Screening of Inorganic Solid Electrolytes for Suppression of Dendrite Formation in Lithium Metal Anodes. ACS Cent. Sci. 2018, 4, 996– 1006, DOI: 10.1021/acscentsci.8b00229Google Scholar442Machine Learning Enabled Computational Screening of Inorganic Solid Electrolytes for Suppression of Dendrite Formation in Lithium Metal AnodesAhmad, Zeeshan; Xie, Tian; Maheshwari, Chinmay; Grossman, Jeffrey C.; Viswanathan, VenkatasubramanianACS Central Science (2018), 4 (8), 996-1006CODEN: ACSCII; ISSN:2374-7951. (American Chemical Society)Next generation batteries based on lithium (Li) metal anodes have been plagued by the dendritic electrodeposition of Li metal on the anode during cycling, resulting in short circuit and capacity loss. Suppression of dendritic growth through the use of solid electrolytes has emerged as one of the most promising strategies for enabling the use of Li metal anodes. We perform a computational screening of over 12000 inorg. solids based on their ability to suppress dendrite initiation in contact with Li metal anode. Properties for mech. isotropic and anisotropic interfaces that can be used in stability criteria for detg. the propensity of dendrite initiation are usually obtained from computationally expensive first-principles methods. In order to obtain a large data set for screening, we use machine-learning models to predict the mech. properties of several new solid electrolytes. The machine-learning models are trained on purely structural features of the material, which do not require any first-principles calcns. We train a graph convolutional neural network on the shear and bulk moduli because of the availability of a large training data set with low noise due to low uncertainty in their first-principles-calcd. values. We use gradient boosting regressor and kernel ridge regression to train the elastic consts., where the choice of the model depends on the size of the training data and the noise that it can handle. The material stiffness is found to increase with an increase in mass d. and ratio of Li and sublattice bond ionicity, and decrease with increase in vol. per atom and sublattice electronegativity. Cross-validation/test performance suggests our models generalize well. We predict over 20 mech. anisotropic interfaces between Li metal and four solid electrolytes which can be used to suppress dendrite growth. Our screened candidates are generally soft and highly anisotropic, and present opportunities for simultaneously obtaining dendrite suppression and high ionic cond. in solid electrolytes.
- 443Tamtaji, M.; Guo, X.; Tyagi, A.; Galligan, P. R.; Liu, Z.; Roxas, A.; Liu, H.; Cai, Y.; Wong, H.; Zeng, L.; Xie, J.; Du, Y.; Hu, Z.; Lu, D.; Goddard, W. A., III; Zhu, Y.; Luo, Z. Machine Learning-Aided Design of Gold Core–Shell Nanocatalysts toward Enhanced and Selective Photooxygenation. ACS Appl. Mater. Interfaces 2022, 14, 46471– 46480, DOI: 10.1021/acsami.2c11101Google Scholar443Machine Learning-Aided Design of Gold Core-Shell Nanocatalysts toward Enhanced and Selective PhotooxygenationTamtaji, Mohsen; Guo, Xuyun; Tyagi, Abhishek; Galligan, Patrick Ryan; Liu, Zhenjing; Roxas, Alexander; Liu, Hongwei; Cai, Yuting; Wong, Hoilun; Zeng, Lun; Xie, Jianbo; Du, Yucong; Hu, Zhigang; Lu, Dong; Goddard III, William A.; Zhu, Ye; Luo, ZhengtangACS Applied Materials & Interfaces (2022), 14 (41), 46471-46480CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)We demonstrate the use of the machine learning (ML) tools to rapidly and accurately predict the elec. field as a guide for designing core-shell Au-silica nanoparticles to enhance 1O2 sensitization and selectivity of org. synthesis. Based on the feature importance anal., obtained from a deep neural network algorithm, we found a general and linear dependent descriptor (θ aD0.25t-1, where a, D, and t are the shape const., size of metal nanoparticles, and distance from the metal surface) for the elec. field around the core-shell plasmonic nanoparticle. Directed by the new descriptor, we synthesized gold-silica nanoparticles and validated their plasmonic intensity using scanning transmission electron microscopy-electron energy loss spectroscopy (STEM-EELS) mapping. The nanoparticles with θ = 0.40 demonstrate an ~ 3-fold increase in the reaction rate of photooxygenation of anthracene and 4% increase in the selectivity of photooxygenation of dihydroartemisinic acid (DHAA), a long-standing goal in org. synthesis. In addn., the combination of ML and exptl. investigations shows the synergetic effect of plasmonic enhancement and fluorescence quenching, leading to enhancement for 1O2 generation. Our results from time-dependent d. functional theory (TD-DFT) calcns. suggest that the presence of an elec. field can favor intersystem crossing (ISC) of methylene blue to enhance 1O2 generation. The strategy reported here provides a data-driven catalyst prepn. method that can significantly reduce exptl. cost while paving the way for designing photocatalysts for org. drug synthesis.
- 444Lussier, F.; Missirlis, D.; Spatz, J. P.; Masson, J.-F. Machine-Learning-Driven Surface-Enhanced Raman Scattering Optophysiology Reveals Multiplexed Metabolite Gradients Near Cells. ACS Nano 2019, 13, 1403– 1411, DOI: 10.1021/acsnano.8b07024Google Scholar444Machine-Learning-Driven Surface-Enhanced Raman Scattering Optophysiology Reveals Multiplexed Metabolite Gradients Near CellsLussier, Felix; Missirlis, Dimitris; Spatz, Joachim P.; Masson, Jean-FrancoisACS Nano (2019), 13 (2), 1403-1411CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)The extracellular environment is a complex medium in which cells secrete and consume metabolites. Mol. gradients are thereby created near cells, triggering various biol. and physiol. responses. However, investigating these mol. gradients remains challenging because the current tools are ill-suited and provide poor temporal and special resoln. while also being destructive. Herein, the authors report the development and application of a machine learning approach in combination with a surface-enhanced Raman spectroscopy (SERS) nanoprobe to measure simultaneously the gradients of at least eight metabolites in vitro near different cell lines. The authors found significant increase in the secretion or consumption of lactate, glucose, ATP, glutamine, and urea within 20 μm from the cells surface compared to the bulk. The authors also obsd. that cancerous cells (HeLa) compared to fibroblasts (REF52) have a greater glycolytic rate, as is expected for this phenotype. Endothelial (HUVEC) and HeLa cells exhibited significant increase in extracellular ATP compared to the control, shining light on the implication of extracellular ATP within the cancer local environment. Machine-learning-driven SERS optophysiol. is generally applicable to metabolites involved in cellular processes, providing a general platform on which to study cell biol.
- 445Shin, H.; Choi, B. H.; Shim, O.; Kim, J.; Park, Y.; Cho, S. K.; Kim, H. K.; Choi, Y. Single test-based diagnosis of multiple cancer types using Exosome-SERS-AI for early stage cancers. Nat. Commun. 2023, 14, 1644, DOI: 10.1038/s41467-023-37403-1Google Scholar445Single test-based diagnosis of multiple cancer types using Exosome-SERS-AI for early stage cancersShin, Hyunku; Choi, Byeong Hyeon; Shim, On; Kim, Jihee; Park, Yong; Cho, Suk Ki; Kim, Hyun Koo; Choi, YeonhoNature Communications (2023), 14 (1), 1644CODEN: NCAOBW; ISSN:2041-1723. (Nature Portfolio)Early cancer detection has significant clin. value, but there remains no single method that can comprehensively identify multiple types of early-stage cancer. Here, we report the diagnostic accuracy of simultaneous detection of 6 types of early-stage cancers (lung, breast, colon, liver, pancreas, and stomach) by analyzing surface-enhanced Raman spectroscopy profiles of exosomes using artificial intelligence in a retrospective study design. It includes classification models that recognize signal patterns of plasma exosomes to identify both their presence and tissues of origin. Using 520 test samples, our system identified cancer presence with an area under the curve value of 0.970. Moreover, the system classified the tumor organ type of 278 early-stage cancer patients with a mean area under the curve of 0.945. The final integrated decision model showed a sensitivity of 90.2% at a specificity of 94.4% while predicting the tumor organ of 72% of pos. patients. Since our method utilizes a non-specific anal. of Raman signatures, its diagnostic scope could potentially be expanded to include other diseases.
- 446Kalinin, S. V.; Kelley, K.; Vasudevan, R. K.; Ziatdinov, M. Toward Decoding the Relationship between Domain Structure and Functionality in Ferroelectrics via Hidden Latent Variables. ACS Appl. Mater. Interfaces 2021, 13, 1693– 1703, DOI: 10.1021/acsami.0c15085Google Scholar446Toward decoding relationship between domain structure and functionality in ferroelectrics via hidden latent variablesKalinin, Sergei V.; Kelley, Kyle; Vasudevan, Rama K.; Ziatdinov, MaximACS Applied Materials & Interfaces (2021), 13 (1), 1693-1703CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Polarization switching mechanisms in ferroelec. materials are fundamentally linked to local domain structure and the presence of the structural defects, which both can act as nucleation and pinning centers and create local electrostatic and mech. depolarization fields affecting wall dynamics. However, the general correlative mechanisms between domain structure and polarization dynamics are only weakly explored, precluding insight into the assocd. phys. mechanisms. Here, the correlation between local domain structures and switching behavior in ferroelec. materials is explored using convolutional encoder-decoder networks, enabling image to spectral (i.m.2spec) and spectral to image (spec2i.m.) translations via encoding of latent variables. The latter reflect the assumption that the relationship between domain structure and polarization switching is parsimonious, i.e., is based upon a small no. of local mechanisms. The anal. of latent variables distributions and their real-space representations provides insight into the predictability of the local switching behavior and hence assocd. phys. mechanisms. We further pose that the regions where these correlative relationships are violated, i.e., predictability of the polarization dynamics from domain structure is reduced, represent the obvious target for detailed studies, e.g., in the context of automated expts. This approach provides a workflow to establish the presence of correlation between local spectral responses and local structure and can be universally applied to spectral imaging techniques such as piezoresponse force microscopy (PFM), scanning tunneling microscopy (STM) and spectroscopy, and electron energy loss spectroscopy (EELS) in scanning transmission electron microscopy (STEM).
- 447Moses, I. A.; Joshi, R. P.; Ozdemir, B.; Kumar, N.; Eickholt, J.; Barone, V. Machine Learning Screening of Metal-Ion Battery Electrode Materials. ACS Appl. Mater. Interfaces 2021, 13, 53355– 53362, DOI: 10.1021/acsami.1c04627Google Scholar447Machine Learning Screening of Metal-Ion Battery Electrode MaterialsMoses, Isaiah A.; Joshi, Rajendra P.; Ozdemir, Burak; Kumar, Neeraj; Eickholt, Jesse; Barone, VeronicaACS Applied Materials & Interfaces (2021), 13 (45), 53355-53362CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Rechargeable batteries provide crucial energy storage systems for renewable energy sources, as well as consumer electronics and elec. vehicles. There are a no. of important parameters that det. the suitability of electrode materials for battery applications, such as the av. voltage and the max. specific capacity which contribute to the overall energy d. Another important performance criterion for battery electrode materials is their vol. change upon charging and discharging, which contributes to det. the cyclability, Coulombic efficiency, and safety of a battery. In this work, we present deep neural network regression machine learning models (ML), trained on data obtained from the Materials Project database, for predicting av. voltages and vol. change upon charging and discharging of electrode materials for metal-ion batteries. Our models exhibit good performance as measured by the av. mean abs. error obtained from a 10-fold cross-validation, as well as on independent test sets. We further assess the robustness of our ML models by investigating their screening potential beyond the training database. We produce Na-ion electrodes by systematically replacing Li-ions in the original database by Na-ions and, then, selecting a set of 22 electrodes that exhibit a good performance in energy d., as well as small vol. variations upon charging and discharging, as predicted by the machine learning model. The ML predictions for these materials are then compared to quantum-mechanics based calcns. Our results reaffirm the significant role of machine learning techniques in the exploration of materials for battery applications.
- 448Garg, A.; Nam, W.; Wang, W.; Vikesland, P.; Zhou, W. In Situ Spatiotemporal SERS Measurements and Multivariate Analysis of Virally Infected Bacterial Biofilms Using Nanolaminated Plasmonic Crystals. ACS Sensors 2023, 8, 1132– 1142, DOI: 10.1021/acssensors.2c02412Google ScholarThere is no corresponding record for this reference.
- 449Matschulat, A.; Drescher, D.; Kneipp, J. Surface-Enhanced Raman Scattering Hybrid Nanoprobe Multiplexing and Imaging in Biological Systems. ACS Nano 2010, 4, 3259– 3269, DOI: 10.1021/nn100280zGoogle Scholar449Surface-Enhanced Raman Scattering Hybrid Nanoprobe Multiplexing and Imaging in Biological SystemsMatschulat, Andrea; Drescher, Daniela; Kneipp, JaninaACS Nano (2010), 4 (6), 3259-3269CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Surface-enhanced Raman scattering (SERS) labels and probes consisting of gold and silver nanoaggregates and attached reporter mols. can be identified by the Raman signature of the reporter mol. At the same time, SERS hybrid probes deliver sensitive mol. structural information on their nanoenvironment. Here the authors demonstrate full exploitation of the multifunctional and multiplexing capabilities inherent to such nanoprobes by applying cluster methods and principal components approaches for discrimination beyond the visual inspection of individual spectra that has been practiced so far. The reported results indicate that fast, multivariate evaluation of whole sets of multiple probes is feasible. Spectra of five different reporters were shown to be separable by hierarchical clustering and by principal components anal. (PCA). In a duplex imaging approach in live cells, hierarchical cluster anal., K-means clustering, and PCA were used for imaging the positions of different types of SERS probes along with the spectral information from cellular constituents. Parallel to cellular imaging expts., cytotoxicity of the SERS hybrid probes contg. arom. thiols as reporters is assessed. The reported results suggest multiplexing applications of the nontoxic SERS nanoprobes in high d. sensing and imaging in complex biol. structures.
- 450Meunier, C. J.; McCarty, G. S.; Sombers, L. A. Drift Subtraction for Fast-Scan Cyclic Voltammetry Using Double-Waveform Partial-Least-Squares Regression. Anal. Chem. 2019, 91, 7319– 7327, DOI: 10.1021/acs.analchem.9b01083Google ScholarThere is no corresponding record for this reference.
- 451Wang, M.; Xu, Q.; Tang, H.; Jiang, J. Machine Learning-Enabled Prediction and High-Throughput Screening of Polymer Membranes for Pervaporation Separation. ACS Appl. Mater. Interfaces 2022, 14, 8427– 8436, DOI: 10.1021/acsami.1c22886Google Scholar451Machine Learning-Enabled Prediction and High-Throughput Screening of Polymer Membranes for Pervaporation SeparationWang, Mao; Xu, Qisong; Tang, Hongjian; Jiang, JianwenACS Applied Materials & Interfaces (2022), 14 (6), 8427-8436CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Pervaporation (PV) is considered as a robust membrane-based sepn. technol. for liq. mixts. However, the development of PV membranes is impeded largely by the lack of adequate models capable of reliably predicting the performance of PV membranes. In this study, we collect an exptl. data set with a total of 681 data samples including 16 polymers and 6 org. solvents for a wide variety of water/org. mixts. under various operating conditions. Then, two types of machine learning (ML) models are developed for prediction and high-throughput screening of polymer membranes for PV sepn. Based on the intrinsic properties of polymer and solvent (water contact angle of polymer and soly. parameter of solvent) as gross descriptors, the first type accurately predicts PV sepn. performance (total flux and sepn. factor). The second type is based on the mol. representation of polymer and solvent, giving accuracy comparable to the first type, and applied to screen ~ 1 million hypothetical polymers for PV sepn. of water/ethanol mixts. With a threshold of 700 for the PV sepn. index, 20 polymers are short listed, with many surpassing exptl. samples. Among these, 10 are further identified to be synthesizable in terms of a synthetic complexity score. The ML models developed in this study would facilitate the optimization of operating conditions and accelerate the development of new polymer membranes for high-performance PV sepn.
- 452Acosta, C. M.; Ogoshi, E.; Souza, J. A.; Dalpian, G. M. Machine Learning Study of the Magnetic Ordering in 2D Materials. ACS Appl. Mater. Interfaces 2022, 14, 9418– 9432, DOI: 10.1021/acsami.1c21558Google Scholar452Machine Learning Study of the Magnetic Ordering in 2D MaterialsAcosta Carlos Mera; Ogoshi Elton; Souza Jose Antonio; Dalpian Gustavo MACS applied materials & interfaces (2022), 14 (7), 9418-9432 ISSN:.Magnetic materials have been applied in a large variety of technologies, from data storage to quantum devices. The development of two-dimensional (2D) materials has opened new arenas for magnetic compounds, even when classical theories discourage their examination. Here we propose a machine-learning-based strategy to predict and understand magnetic ordering in 2D materials. This strategy couples the prediction of the existence of magnetism in 2D materials using a random forest and the Shapley additive explanations method with material maps defined by atomic features predicting the magnetic ordering (ferromagnetic or antiferromagnetic). While the random forest model predicts magnetism with an accuracy of 86%, the material maps obtained by the sure independence screening and sparsifying method have an accuracy of ∼90% in predicting the magnetic ordering. Our model indicates that 3d transition metals, halides, and structural clusters with regular transition-metal sublattices have a positive contribution in the total weight deciding the existence of magnetism in 2D compounds. This behavior is associated with the competition between crystal field and exchange splitting. The machine learning model also indicates that the atomic spin orbit coupling (SOC) is a determinant feature for the identification of the patterns separating ferro- from antiferromagnetic order. The proposed strategy is used to identify novel 2D magnetic compounds that, together with the fundamental trends in the chemical and structural space, pave novel routes for experimental exploration.
- 453Hu, W.; Zhang, L.; Pan, Z. Designing Two-Dimensional Halide Perovskites Based on High-Throughput Calculations and Machine Learning. ACS Appl. Mater. Interfaces 2022, 14, 21596– 21604, DOI: 10.1021/acsami.2c00564Google Scholar453Designing Two-Dimensional Halide Perovskites Based on High-Throughput Calculations and Machine LearningHu, Wenguang; Zhang, Lei; Pan, ZhengACS Applied Materials & Interfaces (2022), 14 (18), 21596-21604CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)The interactions between ions and the low-dimensional halide perovskites are crit. to realizing the next-generation energy storage devices such as photorechargeable ion batteries and ion capacitors. In this study, we performed high-throughput calcns. and machine-learning anal. for ion adsorption on two-dimensional A2BX4 halide perovskites. The first-principles calcns. obtained an initial data set contg. adsorption energies of 640 compositionally engineered ion/perovskite systems with diverse ions including Li+, Zn2+, K+, Na+, Al3+, Ca2+, Mg2+, and F-. The machine learning algorithms including k-nearest neighbors (KNN), Kriging, Random Forest, Rpart, SVM, and Xgboost algorithms were compared, and the Xgboost algorithm achieved the best accuracy (r = 0.97, R2 = 0.93) and was selected to predict the virtual design space consisting of 11 976 ion/perovskite systems. The features were then analyzed and ranked according to their Pearson correlations to the output values. In particular, to better understand the features, diverse feature selection methods were employed to comprehensively evaluate the features. The machine-learning-predicted virtual design space was subsequently screened to select stable lead-free ion/perovskite systems with suitable band gaps and halogen mixing features. The present study provides a theor. foundation to design halide perovskite materials for ion-based energy storage applications such as secondary ion batteries, ion capacitors, and solar-rechargeable batteries.
- 454Alobaidi, M.; Malik, K. M.; Sabra, S. Linked open data-based framework for automatic biomedical ontology generation. BMC Bioinformatics 2018, 19, 319, DOI: 10.1186/s12859-018-2339-3Google ScholarThere is no corresponding record for this reference.
- 455Lu, M.; Gao, F.; Tan, Y.; Yi, H.; Gui, Y.; Xu, Y.; Wang, Y.; Zhou, Y.; Tang, X.; Chen, L. Knowledge-Driven Experimental Discovery of Ce-Based Metal Oxide Composites for Selective Catalytic Reduction of NOx with NH3 through Interpretable Machine Learning. ACS Appl. Mater. Interfaces 2024, 16, 3593– 3604, DOI: 10.1021/acsami.3c18490Google ScholarThere is no corresponding record for this reference.
- 456Huang, Y.; Li, S.; Zhang, L. Accelerated Multisolvent Prediction for Aqueous Stable Halide Perovskite Materials. ACS Appl. Mater. Interfaces 2023, 15, 48771– 48784, DOI: 10.1021/acsami.3c09507Google ScholarThere is no corresponding record for this reference.
- 457Kumar, A.; Islam, M. R.; Zughaier, S. M.; Chen, X.; Zhao, Y. Precision classification and quantitative analysis of bacteria biomarkers via surface-enhanced Raman spectroscopy and machine learning. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 2024, 320, 124627, DOI: 10.1016/j.saa.2024.124627Google ScholarThere is no corresponding record for this reference.
- 458Rosa, L. C. S.; Argolo, C. O.; Nascimento, C. M. C.; Pimentel, A. S. Identifying Substructures That Facilitate Compounds to Penetrate the Blood-Brain Barrier via Passive Transport Using Machine Learning Explainer Models. ACS Chem. Neurosci. 2024, 15, 2144– 2159, DOI: 10.1021/acschemneuro.3c00840Google ScholarThere is no corresponding record for this reference.
- 459Wellawatte, G. P.; Gandhi, H. A.; Seshadri, A.; White, A. D. A Perspective on Explanations of Molecular Prediction Models. J. Chem. Theory Comput. 2023, 19, 2149– 2160, DOI: 10.1021/acs.jctc.2c01235Google Scholar459A Perspective on Explanations of Molecular Prediction ModelsWellawatte, Geemi P.; Gandhi, Heta A.; Seshadri, Aditi; White, Andrew D.Journal of Chemical Theory and Computation (2023), 19 (8), 2149-2160CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)A review. Chemists can be skeptical in using deep learning (DL) in decision making, due to the lack of interpretability in "black-box" models. Explainable artificial intelligence (XAI) is a branch of artificial intelligence (AI) which addresses this drawback by providing tools to interpret DL models and their predictions. We review the principles of XAI in the domain of chem. and emerging methods for creating and evaluating explanations. Then, we focus on methods developed by our group and their applications in predicting soly., blood-brain barrier permeability, and the scent of mols. We show that XAI methods like chem. counterfactuals and descriptor explanations can explain DL predictions while giving insight into structure-property relationships. Finally, we discuss how a two-step process of developing a black-box model and explaining predictions can uncover structure-property relationships.
- 460Wang, S.; Jiang, J. Interpretable Catalysis Models Using Machine Learning with Spectroscopic Descriptors. ACS Catal. 2023, 13, 7428– 7436, DOI: 10.1021/acscatal.3c00611Google Scholar460Interpretable Catalysis Models Using Machine Learning with Spectroscopic DescriptorsWang, Song; Jiang, JunACS Catalysis (2023), 13 (11), 7428-7436CODEN: ACCACS; ISSN:2155-5435. (American Chemical Society)The complexity and dynamics of catalytic systems make it challenging to study the catalysts and catalytic reactions. Fortunately, the advance of machine learning (ML) has made descriptor-based catalyst screening and rational design a mainstream research approach. Herein, the spectroscopic descriptors reported in recent years are highlighted in the field of catalysis. Both vibrational spectra and X-ray absorption spectra have demonstrated strong ability to predict catalytic structures and properties. Through several cases, the interpretable ML models based on spectroscopic descriptors are discussed to reveal phys. knowledge and catalytic mechanism and to exhibit superiority in transfer learning tasks and imperfect data scenarios. Finally, in this Viewpoint, we illustrate the challenges in the research field of interpretable ML models with spectroscopic descriptors and provide perspectives.
- 461Andersen, M.; Reuter, K. Adsorption Enthalpies for Catalysis Modeling through Machine-Learned Descriptors. Acc. Chem. Res. 2021, 54, 2741– 2749, DOI: 10.1021/acs.accounts.1c00153Google Scholar461Adsorption Enthalpies for Catalysis Modeling through Machine-Learned DescriptorsAndersen, Mie; Reuter, KarstenAccounts of Chemical Research (2021), 54 (12), 2741-2749CODEN: ACHRE4; ISSN:0001-4842. (American Chemical Society)A review. Heterogeneous catalysts are rather complex materials that come in many classes (e.g., metals, oxides, carbides) and shapes. At the same time, the interaction of the catalyst surface with even a relatively simple gas-phase environment such as syngas (CO and H2) may already produce a wide variety of reaction intermediates ranging from atoms to complex mols. The starting point for creating predictive maps of, e.g., surface coverages or chem. activities of potential catalyst materials is the reliable prediction of adsorption enthalpies of all of these intermediates. For simple systems, direct d. functional theory (DFT) calcns. are currently the method of choice. However, a wider exploration of complex materials and reaction networks generally requires enthalpy predictions at lower computational cost. The use of machine learning (ML) and related techniques to make accurate and low-cost predictions of quantum mech. calcns. has gained increasing attention lately. The employed approaches span from phys. motivated models over hybrid physics-ΔML approaches to complete black-box methods such as deep neural networks. In recent works the authors have explored the possibilities for using a compressed sensing method (Sure Independence Screening and Sparsifying Operator, SISSO) to identify sparse (low-dimensional) descriptors for the prediction of adsorption enthalpies at various active-site motifs of metals and oxides. The authors start from a set of phys. motivated primary features such as at. acid/base properties, coordination nos., or band moments and let the data and the compressed sensing method find the best algebraic combination of these features. Here the authors take this work as a starting point to categorize and compare recent ML-based approaches with a particular focus on model sparsity, data efficiency, and the level of phys. insight that 1 can obtain from the model. Looking ahead, while many works to date have focused only on the mere prediction of databases of, e.g., adsorption enthalpies, there is also an emerging interest in the field to start using ML predictions to answer fundamental science questions about the functioning of heterogeneous catalysts or perhaps even to design better catalysts than the authors know today. This task is significantly simplified in works that make use of scaling-relation-based models (volcano curves), where the model outcome is detd. by only one or 2 adsorption enthalpies and which consequently become the sole target for ML-based high-throughput screening or design. However, the availability of cheap ML energetics also allows going beyond scaling relations. From the own work in this direction, the authors will discuss the addnl. phys. insight that can be achieved by integrating ML-based predictions with traditional catalysis modeling techniques from thermal and electrocatalysis, such as the computational H electrode and microkinetic modeling, as well as the challenges that lie ahead.
- 462Restuccia, P.; Losi, G.; Chehaimi, O.; Marsili, M.; Righi, M. C. High-Throughput First-Principles Prediction of Interfacial Adhesion Energies in Metal-on-Metal Contacts. ACS Appl. Mater. Interfaces 2023, 15, 19624– 19633, DOI: 10.1021/acsami.3c00662Google Scholar462High-Throughput First-Principles Prediction of Interfacial Adhesion Energies in Metal-on-Metal ContactsRestuccia, Paolo; Losi, Gabriele; Chehaimi, Omar; Marsili, Margherita; Righi, M. CleliaACS Applied Materials & Interfaces (2023), 15 (15), 19624-19633CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Adhesion energy, a measure of the strength by which two surfaces bind together, ultimately dictates the mech. behavior and failure of interfaces. As natural and artificial solid interfaces are ubiquitous, adhesion energy represents a key quantity in a variety of fields ranging from geol. to nanotechnol. Because of intrinsic difficulties in the simulation of systems where two different lattices are matched, and despite their importance, no systematic, accurate first-principles detn. of heterostructure adhesion energy is available. We have developed robust, automatic high-throughput workflow able to fill this gap by systematically searching for the optimal interface geometry and accurately detg. adhesion energies. We apply it here for the first time to perform the screening of around a hundred metallic heterostructures relevant for technol. applications. This allows us to populate a database of accurate values, which can be used as input parameters for macroscopic models. Moreover, it allows us to benchmark commonly used, empirical relations that link adhesion energies to the surface energies of its constituent and to improve their predictivity employing only quantities that are easily measurable or computable.
- 463Trujillo, M. J.; Strausser, S. L.; Becca, J. C.; DeJesus, J. F.; Jensen, L.; Jenkins, D. M.; Camden, J. P. Using SERS To Understand the Binding of N-Heterocyclic Carbenes to Gold Surfaces. J. Phys. Chem. Lett. 2018, 9, 6779– 6785, DOI: 10.1021/acs.jpclett.8b02764Google Scholar463Using SERS To Understand the Binding of N-Heterocyclic Carbenes to Gold SurfacesTrujillo, Michael J.; Strausser, Shelby L.; Becca, Jeffrey C.; DeJesus, Joseph F.; Jensen, Lasse; Jenkins, David M.; Camden, Jon P.Journal of Physical Chemistry Letters (2018), 9 (23), 6779-6785CODEN: JPCLCD; ISSN:1948-7185. (American Chemical Society)Surface functionalization is an essential component of most applications of noble-metal surfaces. Thiols and amines are traditionally employed to attach mols. to noble-metal surfaces, but they have limitations. A growing body of research, however, suggests that N-heterocyclic carbenes (NHCs) can be readily employed for surface functionalization with superior chem. stability compared with thiols. The authors demonstrate the power of surface-enhanced Raman scattering combined with theory to present a comprehensive picture of NHC binding to Au surfaces. In particular, the authors synthesize a library of NHC isotopologues and use surface-enhanced Raman scattering to record the vibrational spectra of these NHCs while bound to Au surfaces. Exptl. data are compared with 1st-principles theory, yielding numerous new insights into the binding of NHCs to Au surfaces. In addn. to these insights, the authors expect approach to be a general method for probing the local surface properties of NHC-functionalized surfaces for their expanding use in sensing applications.
- 464Liu, X.-L.; Leng, Y.-C.; Lin, M.-L.; Cong, X.; Tan, P.-H. Signal-to-noise ratio of Raman signal measured by multichannel detectors*. Chin. Phys. B 2021, 30, 097807 DOI: 10.1088/1674-1056/ac1f06Google ScholarThere is no corresponding record for this reference.
- 465Fang, S.; Wu, S.; Chen, Z.; He, C.; Lin, L. L.; Ye, J. Recent progress and applications of Raman spectrum denoising algorithms in chemical and biological analyses: A review. TrAC Trends in Analytical Chemistry 2024, 172, 117578, DOI: 10.1016/j.trac.2024.117578Google ScholarThere is no corresponding record for this reference.
- 466Zhang, K.; Zuo, W.; Chen, Y.; Meng, D.; Zhang, L. Beyond a Gaussian Denoiser: Residual Learning of Deep CNN for Image Denoising. IEEE Trans. Image Process. 2017, 26, 3142– 3155, DOI: 10.1109/TIP.2017.2662206Google Scholar466Beyond a Gaussian Denoiser: Residual Learning of Deep CNN for Image DenoisingZhang Kai; Zuo Wangmeng; Chen Yunjin; Meng Deyu; Zhang LeiIEEE transactions on image processing : a publication of the IEEE Signal Processing Society (2017), 26 (7), 3142-3155 ISSN:.The discriminative model learning for image denoising has been recently attracting considerable attentions due to its favorable denoising performance. In this paper, we take one step forward by investigating the construction of feed-forward denoising convolutional neural networks (DnCNNs) to embrace the progress in very deep architecture, learning algorithm, and regularization method into image denoising. Specifically, residual learning and batch normalization are utilized to speed up the training process as well as boost the denoising performance. Different from the existing discriminative denoising models which usually train a specific model for additive white Gaussian noise at a certain noise level, our DnCNN model is able to handle Gaussian denoising with unknown noise level (i.e., blind Gaussian denoising). With the residual learning strategy, DnCNN implicitly removes the latent clean image in the hidden layers. This property motivates us to train a single DnCNN model to tackle with several general image denoising tasks, such as Gaussian denoising, single image super-resolution, and JPEG image deblocking. Our extensive experiments demonstrate that our DnCNN model can not only exhibit high effectiveness in several general image denoising tasks, but also be efficiently implemented by benefiting from GPU computing.
- 467Zhang, K.; Zuo, W.; Zhang, L. FFDNet: Toward a Fast and Flexible Solution for CNN-Based Image Denoising. IEEE Trans. Image Process. 2018, 27, 4608– 4622, DOI: 10.1109/TIP.2018.2839891Google ScholarThere is no corresponding record for this reference.
- 468Tian, C.; Xu, Y.; Li, Z.; Zuo, W.; Fei, L.; Liu, H. Attention-guided CNN for image denoising. Neural Networks 2020, 124, 117– 129, DOI: 10.1016/j.neunet.2019.12.024Google Scholar468Attention-guided CNN for image denoisingTian Chunwei; Xu Yong; Li Zuoyong; Zuo Wangmeng; Fei Lunke; Liu HongNeural networks : the official journal of the International Neural Network Society (2020), 124 (), 117-129 ISSN:.Deep convolutional neural networks (CNNs) have attracted considerable interest in low-level computer vision. Researches are usually devoted to improving the performance via very deep CNNs. However, as the depth increases, influences of the shallow layers on deep layers are weakened. Inspired by the fact, we propose an attention-guided denoising convolutional neural network (ADNet), mainly including a sparse block (SB), a feature enhancement block (FEB), an attention block (AB) and a reconstruction block (RB) for image denoising. Specifically, the SB makes a tradeoff between performance and efficiency by using dilated and common convolutions to remove the noise. The FEB integrates global and local features information via a long path to enhance the expressive ability of the denoising model. The AB is used to finely extract the noise information hidden in the complex background, which is very effective for complex noisy images, especially real noisy images and bind denoising. Also, the FEB is integrated with the AB to improve the efficiency and reduce the complexity for training a denoising model. Finally, a RB aims to construct the clean image through the obtained noise mapping and the given noisy image. Additionally, comprehensive experiments show that the proposed ADNet performs very well in three tasks (i.e. synthetic and real noisy images, and blind denoising) in terms of both quantitative and qualitative evaluations. The code of ADNet is accessible at https://github.com/hellloxiaotian/ADNet.
- 469Dabov, K.; Foi, A.; Katkovnik, V.; Egiazarian, K. Image Denoising by Sparse 3-D Transform-Domain Collaborative Filtering. IEEE Trans. Image Process. 2007, 16, 2080– 2095, DOI: 10.1109/TIP.2007.901238Google ScholarThere is no corresponding record for this reference.
- 470Luo, S.-h.; Wang, X.; Chen, G.-y.; Xie, Y.; Zhang, W.-h.; Zhou, Z.-f.; Zhang, Z.-m.; Ren, B.; Liu, G.-k.; Tian, Z.-q. Developing a Peak Extraction and Retention (PEER) Algorithm for Improving the Temporal Resolution of Raman Spectroscopy. Anal. Chem. 2021, 93, 8408– 8413, DOI: 10.1021/acs.analchem.0c05391Google Scholar470Developing a Peak Extraction and Retention (PEER) Algorithm for Improving the Temporal Resolution of Raman SpectroscopyLuo, Si-heng; Wang, Xin; Chen, Gan-yu; Xie, Yi; Zhang, Wen-han; Zhou, Zhi-fan; Zhang, Zhi-min; Ren, Bin; Liu, Guo-kun; Tian, Zhong-qunAnalytical Chemistry (Washington, DC, United States) (2021), 93 (24), 8408-8413CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)In spectroscopic anal., push-to-the-limit sensitivity is one of the important topics, particularly when facing the qual. and quant. analyses of the trace target. Normally, the effective recognition and extn. of weak signals are the first key steps, for which there has been considerable effort in developing various denoising algorithms for decades. Nevertheless, the lower the signal-to-noise ratio (SNR), the greater the deviation of the peak height and shape during the denoising process. Therefore, we propose a denoising algorithm along with peak extn. and retention (PEER). First, both the first and second derivs. of the Raman spectrum are used to det. Raman peaks with a high SNR whose peak information is kept away from the denoising process. Second, an optimized window smoothing algorithm is applied to the left part of the Raman spectrum, which is combined with the untreated Raman peaks to obtain the denoised Raman spectrum. The PEER algorithm is demonstrated with much better signal extn. and retention and successfully improves the temporal resoln. of Raman imaging of a living cell by at least 1 order of magnitude higher than those by traditional algorithms.
- 471He, H.; Cao, M.; Gao, Y.; Zheng, P.; Yan, S.; Zhong, J.-H.; Wang, L.; Jin, D.; Ren, B. Noise learning of instruments for high-contrast, high-resolution and fast hyperspectral microscopy and nanoscopy. Nat. Commun. 2024, 15, 754, DOI: 10.1038/s41467-024-44864-5Google ScholarThere is no corresponding record for this reference.
- 472Lehtinen, J.; Munkberg, J.; Hasselgren, J.; Laine, S.; Karras, T.; Aittala, M.; Aila, T. Noise2Noise: Learning Image Restoration without Clean Data. In International Conference on Machine Learning , 2018; Vol. 80.Google ScholarThere is no corresponding record for this reference.
- 473Wang, X.; Liu, G.; Xu, M.; Ren, B.; Tian, Z. Development of Weak Signal Recognition and an Extraction Algorithm for Raman Imaging. Anal. Chem. 2019, 91, 12909– 12916, DOI: 10.1021/acs.analchem.9b02887Google Scholar473Development of Weak Signal Recognition and an Extraction Algorithm for Raman ImagingWang, Xin; Liu, Guokun; Xu, Mengxi; Ren, Bin; Tian, ZhongqunAnalytical Chemistry (Washington, DC, United States) (2019), 91 (20), 12909-12916CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Improving time resoln. of Raman imaging is essential for the observation of dynamic processes involved in interfacial catalysis and biol. systems. The crucial step is how to recognize and ext. weak Raman signal overwhelmed in the strong noise under the low signal to noise ratio (SNR) condition. Here, by exploring the relationship between SNR of single Raman spectrum and SSIM (the key parameter evaluating image quality) of whole image, the authors detd. a semi-empirical threshold with SNR=0 dB for clear imaging for the first time. Therefore, the authors proposed one signal processing algorithm for fast Raman imaging by reconstructing the Raman spectrum with the aid of weak signal processing: extg. the reliable Raman signal of the target under low signal-noise ratio (SNR), and then detg. the suitable scanning time to obtain the Raman image with trustworthy image quality. In the first step, FFT, least square and 2-D median filter are sequentially applied to improve the SNR of each raw Raman spectrum. In the second step, a local SNR evaluation strategy is developed to predict image quality, as well as the detn. of clear imaging. The proposed method was successfully applied to the fast imaging of cell under low SNR condition.
- 474Tang, Q.; Hu, J.; Chen, J.; Xue, C.; Chen, J.; Dang, H.; Lu, D.; Liu, H.; Sun, Q.; Xiong, Q.; Cong, L.; Shum, P. P. A Two-stage Raman Imaging Denoising Algorithm Based on Deep Learning. In 2022 Asia Communications and Photonics Conference (ACP) , 2022; pp 2096– 2099.Google ScholarThere is no corresponding record for this reference.
- 475Luo, S.-h.; Zhao, X.-j.; Cao, M.-f.; Xu, J.; Wang, W.-l.; Lu, X.-y.; Huang, Q.-t.; Yue, X.-x.; Liu, G.-k.; Yang, L.; Ren, B.; Tian, Z.-q. Signal2signal: Pushing the Spatiotemporal Resolution to the Limit by Single Chemical Hyperspectral Imaging. Anal. Chem. 2024, 96, 6550– 6557, DOI: 10.1021/acs.analchem.3c04609Google ScholarThere is no corresponding record for this reference.
- 476Yu, H.; Zhao, L.; Wang, H. Image Denoising Using Trivariate Shrinkage Filter in the Wavelet Domain and Joint Bilateral Filter in the Spatial Domain. IEEE Trans. Image Process. 2009, 18, 2364– 2369, DOI: 10.1109/TIP.2009.2026685Google ScholarThere is no corresponding record for this reference.
- 477Goyal, B.; Dogra, A.; Agrawal, S.; Sohi, B. S.; Sharma, A. Image denoising review: From classical to state-of-the-art approaches. Information Fusion 2020, 55, 220– 244, DOI: 10.1016/j.inffus.2019.09.003Google ScholarThere is no corresponding record for this reference.
- 478Voulodimos, A.; Doulamis, N.; Doulamis, A.; Protopapadakis, E. Deep Learning for Computer Vision: A Brief Review. Comput. Intell. Neurosci. 2018, 2018, 7068349, DOI: 10.1155/2018/7068349Google Scholar478Deep Learning for Computer Vision: A Brief ReviewVoulodimos Athanasios; Voulodimos Athanasios; Doulamis Nikolaos; Doulamis Anastasios; Protopapadakis EftychiosComputational intelligence and neuroscience (2018), 2018 (), 7068349 ISSN:.Over the last years deep learning methods have been shown to outperform previous state-of-the-art machine learning techniques in several fields, with computer vision being one of the most prominent cases. This review paper provides a brief overview of some of the most significant deep learning schemes used in computer vision problems, that is, Convolutional Neural Networks, Deep Boltzmann Machines and Deep Belief Networks, and Stacked Denoising Autoencoders. A brief account of their history, structure, advantages, and limitations is given, followed by a description of their applications in various computer vision tasks, such as object detection, face recognition, action and activity recognition, and human pose estimation. Finally, a brief overview is given of future directions in designing deep learning schemes for computer vision problems and the challenges involved therein.
- 479Tian, C.; Fei, L.; Zheng, W.; Xu, Y.; Zuo, W.; Lin, C.-W. Deep learning on image denoising: An overview. Neural Networks 2020, 131, 251– 275, DOI: 10.1016/j.neunet.2020.07.025Google Scholar479Deep learning on image denoising: An overviewTian Chunwei; Fei Lunke; Zheng Wenxian; Xu Yong; Zuo Wangmeng; Lin Chia-WenNeural networks : the official journal of the International Neural Network Society (2020), 131 (), 251-275 ISSN:.Deep learning techniques have received much attention in the area of image denoising. However, there are substantial differences in the various types of deep learning methods dealing with image denoising. Specifically, discriminative learning based on deep learning can ably address the issue of Gaussian noise. Optimization models based on deep learning are effective in estimating the real noise. However, there has thus far been little related research to summarize the different deep learning techniques for image denoising. In this paper, we offer a comparative study of deep techniques in image denoising. We first classify the deep convolutional neural networks (CNNs) for additive white noisy images; the deep CNNs for real noisy images; the deep CNNs for blind denoising and the deep CNNs for hybrid noisy images, which represents the combination of noisy, blurred and low-resolution images. Then, we analyze the motivations and principles of the different types of deep learning methods. Next, we compare the state-of-the-art methods on public denoising datasets in terms of quantitative and qualitative analyses. Finally, we point out some potential challenges and directions of future research.
- 480Horgan, C. C.; Jensen, M.; Nagelkerke, A.; St-Pierre, J.-P.; Vercauteren, T.; Stevens, M. M.; Bergholt, M. S. High-Throughput Molecular Imaging via Deep-Learning-Enabled Raman Spectroscopy. Anal. Chem. 2021, 93, 15850– 15860, DOI: 10.1021/acs.analchem.1c02178Google Scholar480High-Throughput Molecular Imaging via Deep-Learning-Enabled Raman SpectroscopyHorgan, Conor C.; Jensen, Magnus; Nagelkerke, Anika; St-Pierre, Jean-Philippe; Vercauteren, Tom; Stevens, Molly M.; Bergholt, Mads S.Analytical Chemistry (Washington, DC, United States) (2021), 93 (48), 15850-15860CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Raman spectroscopy enables nondestructive, label-free imaging with unprecedented mol. contrast, but is limited by slow data acquisition, largely preventing high-throughput imaging applications. Here, we present a comprehensive framework for higher-throughput mol. imaging via deep-learning-enabled Raman spectroscopy, termed DeepeR, trained on a large data set of hyperspectral Raman images, with over 1.5 million spectra (400 h of acquisition) in total. We first perform denoising and reconstruction of low signal-to-noise ratio Raman mol. signatures via deep learning, with a 10x improvement in the mean-squared error over common Raman filtering methods. Next, we develop a neural network for robust 2-4x spatial super-resoln. of hyperspectral Raman images that preserve mol. cellular information. Combining these approaches, we achieve Raman imaging speed-ups of up to 40-90x, enabling good-quality cellular imaging with a high-resoln., high signal-to-noise ratio in under 1 min. We further demonstrate Raman imaging speed-up of 160x, useful for lower resoln. imaging applications such as the rapid screening of large areas or for spectral pathol. Finally, transfer learning is applied to extend DeepeR from cell to tissue-scale imaging. DeepeR provides a foundation that will enable a host of higher-throughput Raman spectroscopy and mol. imaging applications across biomedicine.
- 481Hu, J.; Chen, G. J.; Xue, C.; Liang, P.; Xiang, Y.; Zhang, C.; Chi, X.; Liu, G.; Ye, Y.; Cui, D.; Zhang, D.; yu, X.; Dang, H.; Zhang, W.; Chen, J.; Tang, Q.; Guo, P.; Ho, H.-P.; Li, Y.; Cong, L.; Shum, P. P. RSPSSL: A novel high-fidelity Raman spectral preprocessing scheme to enhance biomedical applications and chemical resolution visualization. Light Sci. Appl. 2024, 13, 52, DOI: 10.1038/s41377-024-01394-5Google ScholarThere is no corresponding record for this reference.
- 482Luo, S.-H.; Pan, S.-Q.; Chen, G.-Y.; Xie, Y.; Ren, B.; Liu, G.-K.; Tian, Z.-Q. Revealing the Denoising Principle of Zero-Shot N2N-Based Algorithm from 1D Spectrum to 2D Image. Anal. Chem. 2024, 96, 4086– 4092, DOI: 10.1021/acs.analchem.3c04608Google ScholarThere is no corresponding record for this reference.
- 483Drumetz, L.; Chanussot, J.; Jutten, C. Variability of the endmembers in spectral unmixing. In Data Handling in Science and Technology; Elsevier: 2019; pp 167– 203.Google ScholarThere is no corresponding record for this reference.
- 484Schmidt, R. W.; Ariese, F.; Omidikia, N. A comparison of multivariate curve resolution with endmember extraction methods in hyperspectral Raman imaging. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 2024, 323, 124868, DOI: 10.1016/j.saa.2024.124868Google ScholarThere is no corresponding record for this reference.
- 485Olmos, V.; Benitez, L.; Marro, M.; Loza-Alvarez, P.; Pina, B.; Tauler, R.; De Juan, A. Relevant aspects of unmixing/resolution analysis for the interpretation of biological vibrational hyperspectral images. TrAC Trends in Analytical Chemistry 2017, 94, 130– 140, DOI: 10.1016/j.trac.2017.07.004Google ScholarThere is no corresponding record for this reference.
- 486Su, X.; Xie, Y.; Liu, X.; Chen, M.; Zheng, C.; Zhong, H.; Li, M. Absolute quantification of serum exosomes in patients with an sers-lateral flow strip biosensor for noninvasive clinical cancer diagnosis. ACS Appl. Mater. Interfaces 2023, 15, 37130– 37142, DOI: 10.1021/acsami.3c05039Google ScholarThere is no corresponding record for this reference.
- 487Haessler, A.; Jung, N.; Windbergs, M. Unraveling Molecular Composition in Biological Samples–Systematic Evaluation of Statistical Methods for the Analysis of Hyperspectral Raman Data. Anal. Chem. 2023, 95, 17646– 17653, DOI: 10.1021/acs.analchem.3c03368Google ScholarThere is no corresponding record for this reference.
- 488Zhang, Y.; Ye, Z.; Li, C.; Chen, Q.; Aljuhani, W.; Huang, Y.; Xu, X.; Wu, C.; Bell, S. E.; Xu, Y. General approach to surface-accessible plasmonic Pickering emulsions for SERS sensing and interfacial catalysis. Nat. Commun. 2023, 14, 1392, DOI: 10.1038/s41467-023-37001-1Google Scholar488General approach to surface-accessible plasmonic Pickering emulsions for SERS sensing and interfacial catalysisZhang, Yingrui; Ye, Ziwei; Li, Chunchun; Chen, Qinglu; Aljuhani, Wafaa; Huang, Yiming; Xu, Xin; Wu, Chunfei; Bell, Steven E. J.; Xu, YikaiNature Communications (2023), 14 (1), 1392CODEN: NCAOBW; ISSN:2041-1723. (Nature Portfolio)Pickering emulsions represent an important class of functional materials with potential applications in sustainability and healthcare. Currently, the synthesis of Pickering emulsions relies heavily on the use of strongly adsorbing mol. modifiers to tune the surface chem. of the nanoparticle constituents. This approach is inconvenient and potentially a dead-end for many applications since the adsorbed modifiers prevent interactions between the functional nanosurface and its surroundings. Here, we demonstrate a general modifier-free approach to construct Pickering emulsions by using a combination of stabilizer particles, which stabilize the emulsion droplet, and a second population of unmodified functional particles that sit alongside the stabilizers at the interface. Freeing Pickering emulsions from chem. modifiers unlocks their potential across a range of applications including plasmonic sensing and interfacial catalysis that have previously been challenging to achieve. More broadly, this strategy provides an approach to the development of surface-accessible nanomaterials with enhanced and/or addnl. properties from a wide range of nano-building blocks including org. nanocrystals, carbonaceous materials, metals and oxides.
- 489Masango, S. S.; Hackler, R. A.; Large, N.; Henry, A.-I.; McAnally, M. O.; Schatz, G. C.; Stair, P. C.; Van Duyne, R. P. High-resolution distance dependence study of surface-enhanced Raman scattering enabled by atomic layer deposition. Nano Lett. 2016, 16, 4251– 4259, DOI: 10.1021/acs.nanolett.6b01276Google Scholar489High-Resolution Distance Dependence Study of Surface-Enhanced Raman Scattering Enabled by Atomic Layer DepositionMasango, Sicelo S.; Hackler, Ryan A.; Large, Nicolas; Henry, Anne-Isabelle; McAnally, Michael O.; Schatz, George C.; Stair, Peter C.; Van Duyne, Richard P.Nano Letters (2016), 16 (7), 4251-4259CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)The authors present a high-resoln. distance dependence study of surface-enhanced Raman scattering (SERS) enabled by at. layer deposition (ALD) at 55 and 100°. ALD is used to deposit monolayers of Al2O3 on bare Ag film over nanospheres (AgFONs) and AgFONs functionalized with self-assembled monolayers. Operando SERS is used to measure the intensities of the Al-Me and C-H stretches from trimethylaluminum (TMA) as a function of distance from the AgFON surface. This study clearly demonstrates that SERS on AgFON substrates displays both a short- and long-range nm scale distance dependence. Agreement is obtained between these expts. and theory that incorporates both short-range and long-range terms. This is a high-resoln. operando SERS distance dependence study performed in 1 integrated expt. using ALD Al2O3 as the spacer layer and Raman label simultaneously. The long-range SERS distance dependence should make it possible to detect chemisorbed surface species located as far as ∼3 nm from the AgFON substrate and will provide new insight into the surface chem. of ALD and catalytic reactions.
- 490Bell, S. E.; Charron, G.; Cortés, E.; Kneipp, J.; de la Chapelle, M. L.; Langer, J.; Procházka, M.; Tran, V.; Schlücker, S. Towards reliable and quantitative surface-enhanced Raman scattering (SERS): from key parameters to good analytical practice. Angew. Chem., Int. Ed. 2020, 59, 5454– 5462, DOI: 10.1002/anie.201908154Google Scholar490Towards Reliable and Quantitative Surface-Enhanced Raman Scattering (SERS): From Key Parameters to Good Analytical PracticeBell, Steven E. J.; Charron, Gaelle; Cortes, Emiliano; Kneipp, Janina; de la Chapelle, Marc Lamy; Langer, Judith; Prochazka, Marek; Tran, Vi; Schluecker, SebastianAngewandte Chemie, International Edition (2020), 59 (14), 5454-5462CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. Exptl. results obtained in different labs. world-wide by researchers using surface-enhanced Raman scattering (SERS) can differ significantly. The authors, an international team of scientists with long-standing expertise in SERS, address this issue from the perspective by presenting considerations on reliable and quant. SERS. The central idea of this joint effort is to highlight key parameters and pitfalls that are often encountered in the literature. To that end, the authors provide here recommendations on: (a) the characterization of solid and colloidal SERS substrates by correlative electron and optical microscopy and spectroscopy, (b) the detn. of the SERS enhancement factor, including suitable Raman reporter/probe mols., and (c) good anal. practice. Hopefully newcomers and specialists will benefit from these recommendations to increase the inter-lab. comparability of exptl. SERS results and further establish SERS as an anal. tool.
- 491Villa, J. E. L.; Pasquini, C.; Poppi, R. J. Surface-enhanced Raman spectroscopy and MCR-ALS for the selective sensing of urinary adenosine on filter paper. Talanta 2018, 187, 99– 105, DOI: 10.1016/j.talanta.2018.05.022Google Scholar491Surface-enhanced Raman spectroscopy and MCR-ALS for the selective sensing of urinary adenosine on filter paperVilla, Javier E. L.; Pasquini, Celio; Poppi, Ronei J.Talanta (2018), 187 (), 99-105CODEN: TLNTA2; ISSN:0039-9140. (Elsevier B.V.)Adenosine is a purine nucleoside that is present in all human cells and is essential for regulating certain physiol. activities in tissues and organs. Since adenosine is considered to be a potential cancer biomarker in urine, its detn. may be crucial for the early diagnosis and non-invasive monitoring of cancer. Herein, we present a label-free method to quantify urinary adenosine using surface-enhanced Raman spectroscopy (SERS) and multivariate curve resoln.-alternating least squares (MCR-ALS). Ring-oven preconcn. and direct deposition of monodisperse gold nanoparticles on filter paper were employed to improve the sampling efficiency. Further, MCR-ALS (assessed with and without a correlation constraint), the std. addn. method and pH controls were combined to compensate for the matrix effect and to address overlapping bands in the anal. of human urine samples. As a result, the proposed method showed to be sensitive (LOD varying between 3.8 and 4.9 μmol L-1, S/R = 3), reproducible (RSD less than ± 15%), and selective over other nucleosides (guanosine, cytidine, thymidine and uridine) and unknown interferences (second-order advantage). This is the first report of a SERS-chemometric method applied to urinary adenosine sensing at physiol. relevant concns., with minimal sample prepn., and has strong potential to be a valuable tool in cancer research.
- 492He, J.; Abdel-Galeil, M. M.; Nemoto, M.; Kishimoto, N.; Morita, S.-i. Bio-Raman non-negative matrix factorization: its practical methodology. Applied Physics Express 2023, 16, 026502 DOI: 10.35848/1882-0786/acb6ceGoogle ScholarThere is no corresponding record for this reference.
- 493Deng, X.; Milligan, K.; Ali-Adeeb, R.; Shreeves, P.; Brolo, A.; Lum, J. J.; Andrews, J. L.; Jirasek, A. Group and basis restricted non-negative matrix factorization and random forest for molecular histotype classification and Raman biomarker monitoring in breast cancer. Applied spectroscopy 2022, 76, 462– 474, DOI: 10.1177/00037028211035398Google ScholarThere is no corresponding record for this reference.
- 494Lobanova, E.; Lobanov, S. Efficient quantitative hyperspectral image unmixing method for large-scale Raman micro-spectroscopy data analysis. Anal. Chim. Acta 2019, 1050, 32– 43, DOI: 10.1016/j.aca.2018.11.018Google Scholar494Efficient quantitative hyperspectral image unmixing method for large-scale Raman micro-spectroscopy data analysisLobanova, E. G.; Lobanov, S. V.Analytica Chimica Acta (2019), 1050 (), 32-43CODEN: ACACAM; ISSN:0003-2670. (Elsevier B.V.)Vibrational micro-spectroscopy is a powerful optical tool, providing a non-invasive label-free chem. specific imaging for many chem. and biomedical applications. However, hyperspectral image produced by Raman micro-spectroscopy typically consists of thousands discrete pixel points, each having individual Raman spectrum at thousand wavenumbers, and therefore requires appropriate image unmixing computational methods to retrieve non-neg. spatial concn. and corresponding non-neg. spectra of the image biochem. constituents. Here, we present a new efficient Quant. Hyperspectral Image Unmixing (Q-HIU) method for large-scale Raman micro-spectroscopy data anal. This method enables to simultaneously analyze multi-set Raman hyperspectral images in three steps: (i) Singular Value Decompn. with innovative Automatic Divisive Correlation which autonomously filters spatially and spectrally uncorrelated noise from data; (ii) a robust subtraction of fluorescent background from the data using a newly developed algorithm called Bottom Gaussian Fitting; (iii) an efficient Quant. Unsupervised/Partially Supervised Non-neg. Matrix Factorization method, which rigorously retrieves non-neg. spatial concn. maps and spectral profiles of the samples' biochem. constituents with no a priori information or when one or several samples' constituents are known. As compared with state-of-the-art methods, our approach allows to achieve significantly more accurate results and efficient quantification with several orders of magnitude shorter computational time as verified on both artificial and real exptl. data. We apply Q-HIU to the anal. of large-scale Raman hyperspectral images of human atherosclerotic aortic tissues and our results show a proof-of-principle for the proposed method to retrieve and quantify the biochem. compn. of the tissues, consisting of both high and low concd. compds. Along with the established hallmarks of atherosclerosis including cholesterol/cholesterol ester, triglyceride and calcium hydroxyapatite crystals, our Q-HIU allowed to identify the significant accumulations of oxidatively modified lipids co-localizing with the atherosclerotic plaque lesions in the aortic tissues, possibly reflecting the persistent presence of inflammation and oxidative damage in these regions, which are in turn able to promote the disease pathol. For minor chem. components in the diseased tissues, our Q-HIU was able to detect the signatures of calcium hydroxyapatite and β-carotene with relative mean Raman concns. as low as 0.09% and 0.04% from the original Raman intensity matrix with noise and fluorescent background contributions of 3% and 94%, resp.
- 495Kneipp, J.; Kneipp, K. Surface Enhanced Nonlinear Raman Processes for Advanced Vibrational Probing. ACS Nano 2024, 18, 20851– 20860, DOI: 10.1021/acsnano.4c07508Google ScholarThere is no corresponding record for this reference.
- 496Zhao, F.; Zheng, Y.; Zhao, Z.; Wang, W.; Xu, T.; Xue, X.; Fu, W.; Ling, Y.; Shi, J.; Zhang, Z. Re-understanding of SERS for General and Standardized Quantitative Analysis. Nano Lett. 2024, 24, 10290, DOI: 10.1021/acs.nanolett.4c02789Google ScholarThere is no corresponding record for this reference.
- 497Xu, Y.; Aljuhani, W.; Zhang, Y.; Ye, Z.; Li, C.; Bell, S. E. J. A practical approach to quantitative analytical surface-enhanced Raman spectroscopy. Chem. Soc. Rev. 2025, 54, 62– 84, DOI: 10.1039/D4CS00861HGoogle ScholarThere is no corresponding record for this reference.
- 498Su, M.; Wang, C.; Wang, T.; Jiang, Y.; Xu, Y.; Liu, H. Breaking the affinity limit with dual-phase-accessible hotspot for ultrahigh Raman scattering of nonadsorptive molecules. Anal. Chem. 2020, 92, 6941– 6948, DOI: 10.1021/acs.analchem.9b05727Google Scholar498Breaking the Affinity Limit with Dual-Phase-Accessible Hotspot for Ultrahigh Raman Scattering of Nonadsorptive MoleculesSu, Mengke; Wang, Chao; Wang, Tengfei; Jiang, Yifan; Xu, Yue; Liu, HonglinAnalytical Chemistry (Washington, DC, United States) (2020), 92 (10), 6941-6948CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)For surface-enhanced Raman scattering (SERS) anal., only analytes that can be absorbed spontaneously onto a noble metal surface can be detected effectively. Therefore, getting nonadsorptive mols. close enough to the surface has always been a key challenge in SERS anal. Here absorbance measurements show that the liq.-interfacial array (LIA) does not adsorb or enrich benzopyrene (Bap) mols., which lack effective functional groups that can interact with the noble metal surfaces. But the SERS intensity of 0.1 ppm Bap on the LIA is 10 times larger than that of 10 ppm Bap on traditional solid substrate, i.e., 3 orders of magnitude of enhancement. The LIA overcomes the restriction of affinity between Bap mols. and the metal surface, and the Bap mols. can easily enter nanogaps without steric hindrance. Furthermore, both adsorptive and nonadsorptive mols. were used to observe the SERS enhancement behavior on the LIA platforms. In multiple detection, competitive SERS signal changes could be obsd. between adsorptive and nonadsorptive mols. or between nonadsorptive and nonadsorptive mols. A theor. scheme was profiled for localized surface plasmon resonance (SPR) properties of the LIA. Finite difference-time domain (FDTD) simulation shows that the LIAs have biphasic and accessible asym. hotspots, and the elec. field enhancement in the CHCl3 (O) phase is approx. four times larger than that of the water (W) phase. In addn., the position and relative strength of the electromagnetic field depend on the spatial position of gold nanoparticles (GNPs) relative to the liq.-liq. interface (LLI), i.e., when the GNP dimer is completely immersed in a certain phase, the electromagnetic field enhancement of the CHCl3 phase is approx. 7 times larger than that of the W phase. We speculate that dual-phase-accessible hotspots and the hydrophobic environment provided by CHCl3 are two important factors contributing to successful detection of four common polycyclic arom. hydrocarbons (PAHs) with a detection limit of 10 ppb. Finally, the LIA platform successfully realizes simultaneous detection of multiple PAHs in both plant and animal oils with good stability. This study provides a new direction for the development of high-efficiency and practical SERS technol. for nonadsorptive mols.
- 499Morton, S. M.; Jensen, L. Understanding the molecule– surface chemical coupling in SERS. J. Am. Chem. Soc. 2009, 131, 4090– 4098, DOI: 10.1021/ja809143cGoogle Scholar499Understanding the Molecule-Surface Chemical Coupling in SERSMorton, Seth M.; Jensen, LasseJournal of the American Chemical Society (2009), 131 (11), 4090-4098CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)The enhancement mechanism due to the mol.-surface chem. coupling in surface-enhanced Raman scattering (SERS) was characterized using time-dependent d. functional theory. This was achieved with a systematical study of the chem. enhancement of meta- and para-substituted pyridines interacting with a small silver cluster (Ag20). Changing the functional groups on pyridine enabled one to modulate the direct chem. interactions between the pyridine ring and the metal cluster. Surprisingly, the enhancement does not increase as more charge is transferred from the pyridine ring to the cluster. Instead, the magnitude of chem. enhancement is governed to a large extent by the energy difference between the highest occupied energy level (HOMO) of the metal and the lowest unoccupied energy level (LUMO) of the mol. The enhancement scales roughly as (ωX/‾ωe)4, where ‾ωe is an av. excitation energy between the HOMO of the metal and the LUMO of the mol. and ωX is the HOMO-LUMO gap of the free mol. The trend was verified by considering substituted benzenethiols, small mols., and silver clusters of varying sizes. The results imply that mols. that show significant stabilization of the HOMO-LUMO gaps (such as those that readily accept π-backbonding) would be likely to have strong chem. enhancement. The findings presented here provide the framework for designing new mols. which exhibit high chem. enhancements. However, it remains a challenge to accurately describe the magnitude of the Raman enhancements using electronic structure methods, esp. d. functional theory, because they often underestimate the energy gap.
- 500Su, Y.-Q.; Liu, J.; Huang, R.; Yang, H.-T.; Li, M.-X.; Pang, R.; Zhang, M.; Yang, M.-H.; Su, H.-F.; Devasenathipathy, R.; Wu, Y.-F.; Zhou, J.-Z.; Wu, D.-Y.; Xie, S.-Y.; Mao, B.-W.; Tian, Z.-Q. Plasmon-Mediated Photoelectrochemical Hot-Hole Oxidation Coupling Reactions of Adenine on Nanostructured Silver Electrodes. J. Phys. Chem. Lett. 2023, 14, 5163– 5171, DOI: 10.1021/acs.jpclett.3c00619Google Scholar500Plasmon-Mediated Photoelectrochemical Hot-Hole Oxidation Coupling Reactions of Adenine on Nanostructured Silver ElectrodesSu, Ya-Qiong; Liu, Jia; Huang, Rong; Yang, Hong-Tao; Li, Ming-Xue; Pang, Ran; Zhang, Meng; Yang, Meng-Han; Su, Hai-Feng; Devasenathipathy, Rajkumar; Wu, Yuan-Fei; Zhou, Jian-Zhang; Wu, De-Yin; Xie, Su-Yuan; Mao, Bing-Wei; Tian, Zhong-QunJournal of Physical Chemistry Letters (2023), 14 (22), 5163-5171CODEN: JPCLCD; ISSN:1948-7185. (American Chemical Society)Surface-enhanced Raman spectroscopy (SERS) has been widely applied in the identification and characterization of DNA structures with high efficiency. Esp., the SERS signals of the adenine group have exhibited high detection sensitivity in several biomol. systems. However, there is still no unanimous conclusion regarding the interpretation of some special kinds of SERS signals of adenine and its derivs. on silver colloids and electrodes. This Letter presents a new photochem. azo coupling reaction for adenyl residues, in which the adenine is selectively oxidized to (E)-1,2-di(7H-purin-6-yl) diazene (azopurine) in the presence of silver ions, silver colloids, and electrodes of nanostructures under visible light irradn. The product, azopurine, is first found to be responsible for the SERS signals. This photoelectrochem. oxidative coupling reaction of adenine and its derivs. is promoted by plasmon-mediated hot holes and is regulated by pos. potentials and pH of solns., which opens up new avenues for studying azo coupling in the photoelectrochem. of adenine-contg. biomols. on electrode surfaces of plasmonic metal nanostructures.
- 501Cabalo, J.; Guicheteau, J. A.; Christesen, S. Toward understanding the influence of intermolecular interactions and molecular orientation on the chemical enhancement of SERS. J. Phys. Chem. A 2013, 117, 9028– 9038, DOI: 10.1021/jp403458kGoogle Scholar501Toward Understanding the Influence of Intermolecular Interactions and Molecular Orientation on the Chemical Enhancement of SERSCabalo, Jerry; Guicheteau, Jason A.; Christesen, StevenJournal of Physical Chemistry A (2013), 117 (37), 9028-9038CODEN: JPCAFH; ISSN:1089-5639. (American Chemical Society)Implementation of SERS as an anal. technique is limited because the factors that govern the enhancement of individual vibrational modes are not well understood. Although the chem. effect only accounts for up to 2 orders of magnitude enhancement, it can still have a significant impact on the consistency of chem. spectral signatures. The authors report on a combined theor. and exptl. study on the benzenethiol on Ag and 4-mercaptophenol on Ag systems. The primary and unique finding was that for the benzenethiol on Ag system the inclusion of interaction between multiple benzenethiol analyte mols. was essential to account for the relative enhancements obsd. exptl. An examn. of the MOs showed sharing of electron d. across the entire model of multiple benzenethiol mols. mediated by the metal atoms. The addn. of multiple 4-mercaptophenol mols. to the theor. model had little effect on the predicted spectra, and the authors attribute this to the fact that a much larger model is necessary to replicate the networks of H bonds. Mol. orientation was also found to affect the predicted spectra, and an upright position improved agreement between theor. and exptl. spectra. An anal. of the vibrational frequency shifts between the normal Raman spectrum of the neat compd. and the SERS spectrum also suggests that both benzenethiol and 4-mercaptophenol are in an upright position.
- 502Burzynski, N.; Yuan, Y.; Felsen, A.; Reitano, D.; Wang, Z.; Sethi, K. A.; Lu, F.; Chiu, K. In Deep learning techniques for unmixing of hyperspectral stimulated raman scattering images. In 2021 IEEE International Conference on Big Data (Big Data) , 2021; pp 5862– 5864.Google ScholarThere is no corresponding record for this reference.
- 503Qu, Y.; Qi, H. uDAS: An untied denoising autoencoder with sparsity for spectral unmixing. IEEE Transactions on Geoscience and Remote Sensing 2019, 57, 1698– 1712, DOI: 10.1109/TGRS.2018.2868690Google ScholarThere is no corresponding record for this reference.
- 504Georgiev, D.; Fernandez-Galiana, A.; Vilms Pedersen, S.; Papadopoulos, G.; Xie, R.; Stevens, M. M.; Barahona, M. Hyperspectral unmixing for Raman spectroscopy via physics-constrained autoencoders. arXiv Preprint , arXiv:2403.04526, 2024. DOI: 10.1073/pnas.2407439121Google ScholarThere is no corresponding record for this reference.
- 505Su, Y.; Li, J.; Plaza, A.; Marinoni, A.; Gamba, P.; Chakravortty, S. DAEN: Deep autoencoder networks for hyperspectral unmixing. IEEE Transactions on Geoscience and Remote Sensing 2019, 57, 4309– 4321, DOI: 10.1109/TGRS.2018.2890633Google ScholarThere is no corresponding record for this reference.
- 506Zhang, X.; Sun, Y.; Zhang, J.; Wu, P.; Jiao, L. Hyperspectral unmixing via deep convolutional neural networks. IEEE Geoscience and Remote Sensing Letters 2018, 15, 1755– 1759, DOI: 10.1109/LGRS.2018.2857804Google ScholarThere is no corresponding record for this reference.
- 507Hong, D.; Gao, L.; Yao, J.; Yokoya, N.; Chanussot, J.; Heiden, U.; Zhang, B. Endmember-guided unmixing network (EGU-Net): A general deep learning framework for self-supervised hyperspectral unmixing. IEEE Transactions on Neural Networks and Learning Systems 2022, 33, 6518– 6531, DOI: 10.1109/TNNLS.2021.3082289Google ScholarThere is no corresponding record for this reference.
- 508Ghosh, P.; Roy, S. K.; Koirala, B.; Rasti, B.; Scheunders, P. Hyperspectral unmixing using transformer network. IEEE Transactions on Geoscience and Remote Sensing 2022, 60, 1– 16, DOI: 10.1109/TGRS.2022.3196057Google ScholarThere is no corresponding record for this reference.
- 509Shahid, K. T.; Schizas, I. D. Unsupervised hyperspectral unmixing via nonlinear autoencoders. IEEE Transactions on Geoscience and Remote Sensing 2022, 60, 1– 13, DOI: 10.1109/TGRS.2021.3077833Google ScholarThere is no corresponding record for this reference.
- 510Bai, S.; Serien, D.; Ma, Y.; Obata, K.; Sugioka, K. Attomolar Sensing Based on Liquid Interface-Assisted Surface-Enhanced Raman Scattering in Microfluidic Chip by Femtosecond Laser Processing. ACS Appl. Mater. Interfaces 2020, 12, 42328– 42338, DOI: 10.1021/acsami.0c11322Google Scholar510Attomolar Sensing Based on Liquid Interface-Assisted Surface-Enhanced Raman Scattering in Microfluidic Chip by Femtosecond Laser ProcessingBai, Shi; Serien, Daniela; Ma, Ying; Obata, Kotaro; Sugioka, KojiACS Applied Materials & Interfaces (2020), 12 (37), 42328-42338CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Surface-enhanced Raman scattering (SERS) is a multidisciplinary trace anal. technique based on plasmonic effects. The development of SERS microfluidic chips has been exploited extensively in recent times impacting on applications in diverse fields. However, despite much progress, the excitation of label-free mols. is extremely challenging when analyte concns. are <1 nM because of the blinking SERS effect. A novel anal. strategy which can achieve detection limits at an attomolar level is proposed. This performance improvement is due to the use of a glass microfluidic chip that features an analyte air-soln. interface which forms on the SERS substrate in the microfluidic channel, whereby the analyte mols. aggregate locally at the interface during the measurement, hence the term liq. interface-assisted SERS (LI-SERS). The microfluidic chips are fabricated using hybrid femtosecond (fs) laser processing consisting of fs laser-assisted chem. etching, selective metalization, and metal surface nanostructuring. The novel LI-SERS technique can achieve an anal. enhancement factor of 1.5 × 1014, providing a detection limit <10-17 M (<10 aM). The mechanism for the extraordinary enhancement afforded by LI-SERS is attributed to Marangoni convection induced by the photothermal effect.
- 511Hao, Q.; Li, M.; Wang, J.; Fan, X.; Jiang, J.; Wang, X.; Zhu, M.; Qiu, T.; Ma, L.; Chu, P. K.; Schmidt, O. G. Flexible Surface-Enhanced Raman Scattering Chip: A Universal Platform for Real-Time Interfacial Molecular Analysis with Femtomolar Sensitivity. ACS Appl. Mater. Interfaces 2020, 12, 54174– 54180, DOI: 10.1021/acsami.0c16315Google Scholar511Flexible Surface-Enhanced Raman Scattering Chip: A Universal Platform for Real-Time Interfacial Molecular Analysis with Femtomolar SensitivityHao, Qi; Li, Mingze; Wang, Jiawei; Fan, Xingce; Jiang, Jie; Wang, Xiaoxia; Zhu, Minshen; Qiu, Teng; Ma, Libo; Chu, Paul K.; Schmidt, Oliver G.ACS Applied Materials & Interfaces (2020), 12 (48), 54174-54180CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)We propose and demonstrate a flexible surface-enhanced Raman scattering (SERS) chip as a versatile platform for femtomolar detection and real-time interfacial mol. anal. The flexible SERS chip is composed of a flexible and transparent membrane and embedded plasmonic dimers with ultrahigh particle d. and ultrasmall dimer gap. The chip enables rapid identification for residuals on solid substrates with irregular surfaces or dissolved analytes in aq. soln. The sensitivity for liq.-state measurement is down to 0.06 mol. per dimers for 10-14 mol·L-1 Rhodamine 6G mol. without mol. enrichment. Strong signal fluctuation and blinking are obsd. at this concn., indicating that the detection limit is close to the single-mol. level. Meanwhile, the homogeneous liq. environment facilities accurate SERS quantification of analytes with a wide dynamic range. The synergy of flexibility and liq.-state measurement opens up avenues for the real-time study of chem. reactions. The redn. from p-nitrothiophenol (PNTP) to p-aminothiophenol (PATP) in the absence of the chem. reducing agents is obsd. at liq. interfaces by in situ SERS measurements, and the plasmon-induced hot electron is demonstrated to drive the catalytic reaction. We believe this robust and feasible approach is promising in extending the SERS technique as a general method for identifying interfacial mol. traces, tracking the evolution of heterogeneous reactions, elucidating the reaction mechanisms, and evaluating the environmental effects such as pH value and salty ions in SERS.
- 512Bhavya, M. B.; Prabhu, B. R.; Shenoy, B. M.; Bhol, P.; Swain, S.; Saxena, M.; John, N. S.; Hegde, G.; Samal, A. K. Femtomolar detection of thiram via SERS using silver nanocubes as an efficient substrate. Environmental Science: Nano 2020, 7, 3999– 4009, DOI: 10.1039/D0EN01049AGoogle ScholarThere is no corresponding record for this reference.
- 513Yu, Y.; Xiao, T.-H.; Wu, Y.; Li, W.; Zeng, Q.-G.; Long, L.; Li, Z.-Y. Roadmap for single-molecule surface-enhanced Raman spectroscopy. Advanced Photonics 2020, 2, 014002 DOI: 10.1117/1.AP.2.1.014002Google Scholar513Roadmap for single-molecule surface-enhanced Raman spectroscopyYu, Yang; Xiao, Ting-Hui; Wu, Yunzhao; Li, Wanjun; Zeng, Qing-Guang; Long, Li; Li, Zhi-YuanAdvanced Photonics (2020), 2 (1), 014002CODEN: APDHC9; ISSN:2577-5421. (Society of Photo-Optical Instrumentation Engineers)In the near future, single-mol. surface-enhanced Raman spectroscopy (SERS) is expected to expand the family of popular anal. tools for single-mol. characterization. We provide a roadmap for achieving single mol. SERS through different enhancement strategies for diverse applications. We introduce some characteristic features related to single-mol. SERS, such as Raman enhancement factor, intensity fluctuation, and data anal. We then review recent strategies for enhancing the Raman signal intensities of single mols., including electromagnetic enhancement, chem. enhancement, and resonance enhancement strategies. To demonstrate the utility of single-mol. SERS in practical applications, we present several examples of its use in various fields, including catalysis, imaging, and nanoelectronics. Finally, we specify current challenges in the development of single-mol. SERS and propose corresponding solns.
- 514Qian, X. M.; Nie, S. M. Single-molecule and single-nanoparticle SERS: from fundamental mechanisms to biomedical applications. Chem. Soc. Rev. 2008, 37, 912– 920, DOI: 10.1039/b708839fGoogle Scholar514Single-molecule and single-nanoparticle SERS: from fundamental mechanisms to biomedical applicationsQian, X.-M.; Nie, S. M.Chemical Society Reviews (2008), 37 (5), 912-920CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)This tutorial review discusses a new class of colloidal metal nanoparticles that is able to enhance the efficiencies of surface-enhanced Raman scattering (SERS) by as much as 1014-1015 fold. This enormous enhancement allows spectroscopic detection and identification of single mols. located on the nanoparticle surface or at the junction of two particles under ambient conditions. Considerable progress has been made in understanding the enhancement mechanisms, including definitive evidence for the single-mol. origin of fluctuating SERS signals. For applications, SERS nanoparticle tags have been developed based on the use of embedded reporter mols. and a silica or polymer encapsulation layer. The SERS nanoparticle tags are capable of providing detailed spectroscopic information and are much brighter than semiconductor quantum dots in the near-IR spectral window. These properties have raised new opportunities for multiplexed mol. diagnosis and in vivo Raman spectroscopy and imaging.
- 515Le Ru, E. C.; Meyer, M.; Etchegoin, P. G. Proof of Single-Molecule Sensitivity in Surface Enhanced Raman Scattering (SERS) by Means of a Two-Analyte Technique. J. Phys. Chem. B 2006, 110, 1944– 1948, DOI: 10.1021/jp054732vGoogle Scholar515Proof of Single-Molecule Sensitivity in Surface Enhanced Raman Scattering (SERS) by Means of a Two-Analyte TechniqueLe Ru, E. C.; Meyer, M.; Etchegoin, P. G.Journal of Physical Chemistry B (2006), 110 (4), 1944-1948CODEN: JPCBFK; ISSN:1520-6106. (American Chemical Society)A method is proposed to pin down unambiguous proof for single-mol. sensitivity in surface enhanced Raman spectroscopy (SERS). The simultaneous use of two analyte mols. enables a clear confirmation of the single (or few)-mol. nature of the signals. This method eliminates most of the uncertainties assocd. with low dye concns. in previous expts. It further shows that single- or few-mol. signals are very common in SERS, both in liqs. and on dry substrates.
- 516Lindquist, N. C.; de Albuquerque, C. D. L.; Sobral-Filho, R. G.; Paci, I.; Brolo, A. G. High-speed imaging of surface-enhanced Raman scattering fluctuations from individual nanoparticles. Nat. Nanotechnol. 2019, 14, 981– 987, DOI: 10.1038/s41565-019-0535-6Google Scholar516High-speed imaging of surface-enhanced Raman scattering fluctuations from individual nanoparticlesLindquist, Nathan C.; de Albuquerque, Carlos Diego L.; Sobral-Filho, Regivaldo G.; Paci, Irina; Brolo, Alexandre G.Nature Nanotechnology (2019), 14 (10), 981-987CODEN: NNAABX; ISSN:1748-3387. (Nature Research)The concept of plasmonic hotspots is central to the interpretation of the surface-enhanced Raman scattering (SERS) effect. Although plasmonic hotspots are generally portrayed as static features, single-mol. SERS (SM-SERS) is marked by characteristic time-dependent fluctuations in signal intensity. The origin of those fluctuations can be assigned to a variety of dynamic and complex processes, including mol. adsorption or desorption, surface diffusion, mol. reorientation and metal surface reconstruction. Since each of these mechanisms simultaneously contributes to a fluctuating SERS signal, probing their relative impact in SM-SERS remains an exptl. challenge. Here, we introduce a super-resoln. imaging technique with an acquisition rate of 800,000 frames per s to probe the spatial and temporal features of the SM-SERS fluctuations from single silver nanoshells. The technique has a spatial resoln. of ∼7 nm. The images reveal short ∼10 μs scattering events localized in various regions on a single nanoparticle. Remarkably, even a fully functionalized nanoparticle was 'dark' more than 98% of the time. The sporadic SERS emission suggests a transient hotspot formation mechanism driven by a random reconstruction of the metallic surface, an effect that dominates over any plasmonic resonance of the particle itself. Our results provide the SERS community with a high-speed exptl. approach to study the fast dynamic properties of SM-SERS hotspots in typical room-temp. exptl. conditions, with possible implications in catalysis and sensing.
- 517de Albuquerque, C. D. L.; Hokanson, K. M.; Thorud, S. R.; Sobral-Filho, R. G.; Lindquist, N. C.; Brolo, A. G. Dynamic Imaging of Multiple SERS Hotspots on Single Nanoparticles. ACS Photonics 2020, 7, 434– 443, DOI: 10.1021/acsphotonics.9b01395Google Scholar517Dynamic Imaging of Multiple SERS Hotspots on Single Nanoparticlesde Albuquerque, Carlos Diego L.; Hokanson, Kallai M.; Thorud, Sarah R.; Sobral-Filho, Regivaldo G.; Lindquist, Nathan C.; Brolo, Alexandre G.ACS Photonics (2020), 7 (2), 434-443CODEN: APCHD5; ISSN:2330-4022. (American Chemical Society)Signal intensity fluctuations are a ubiquitous characteristic of single-mol. surface-enhanced Raman scattering (SERS). In this work, we obsd. SERS intensity fluctuations (SIFs) from single nanoparticles fully coated with an adsorbate layer. Fluctuations from dry, fully coated nanoparticles are assigned to a dynamic mol./metal environment wherein at.-scale reconstructions support SERS. Using super resoln. imaging techniques, we were able to pinpoint the positions of the fluctuations with subparticle precision. We obsd. that the fluctuation events were sepd. spatially, temporally, and were unique to different laser excitation wavelengths and polarizations. Dual-wavelength super-resoln. SERS imaging with green and red lasers reveal various classes of SIFs that occur either simultaneously or nonsimultaneously and from either the same or different location on a single nanoparticle. Similar results were seen when the particle is excited with different polarizations. This suggests that single mol. responses from several different hotspots in the same nanoparticle were readily probed. Furthermore, each nanoparticle contains multiple unique hotspots of different strengths, and resonance conditions, which are accessible by the different illumination conditions. The plasmon resonances localized by the roughness features at the nanoparticle's surface play a significant role in the fluctuation events. Our expts. show that SERS hotspots that support single mols. are not a static feature of the nanoparticle. This information should be useful to guide future single-mol. SERS expts.
- 518Son, J.; Kim, G.-H.; Lee, Y.; Lee, C.; Cha, S.; Nam, J.-M. Toward Quantitative Surface-Enhanced Raman Scattering with Plasmonic Nanoparticles: Multiscale View on Heterogeneities in Particle Morphology, Surface Modification, Interface, and Analytical Protocols. J. Am. Chem. Soc. 2022, 144, 22337– 22351, DOI: 10.1021/jacs.2c05950Google Scholar518Toward Quantitative Surface-Enhanced Raman Scattering with Plasmonic Nanoparticles: Multiscale View on Heterogeneities in Particle Morphology, Surface Modification, Interface, and Analytical ProtocolsSon, Jiwoong; Kim, Gyeong-Hwan; Lee, Yeonhee; Lee, Chungyeon; Cha, Seungsang; Nam, Jwa-MinJournal of the American Chemical Society (2022), 144 (49), 22337-22351CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)A review. Surface-enhanced Raman scattering (SERS) provides significantly enhanced Raman scattering signals from mols. adsorbed on plasmonic nanostructures, as well as the mols.' vibrational fingerprints. Plasmonic nanoparticle systems are particularly powerful for SERS substrates as they provide a wide range of structural features and plasmonic couplings to boost the enhancement, often up to >108-1010. Nevertheless, nanoparticle-based SERS is not widely utilized as a means for reliable quant. measurement of mols. largely due to limited controllability, uniformity, and scalability of plasmonic nanoparticles, poor mol. modification chem., and a lack of widely used anal. protocols for SERS. Furthermore, multiscale issues with plasmonic nanoparticle systems that range from at. and mol. scales to assembled nanostructure scale are difficult to simultaneously control, analyze, and address. In this perspective, we introduce and discuss the design principles and key issues in prepg. SERS nanoparticle substrates and the recent studies on the uniform and controllable synthesis and newly emerging machine learning-based anal. of plasmonic nanoparticle systems for quant. SERS. Specifically, the multiscale point of view with plasmonic nanoparticle systems toward quant. SERS is provided throughout this perspective. Furthermore, issues with correctly estg. and comparing SERS enhancement factors are discussed, and newly emerging statistical and artificial intelligence approaches for analyzing complex SERS systems are introduced and scrutinized to address challenges that cannot be fully resolved through synthetic improvements.
- 519Porter, M. D.; Granger, J. H. Surface-enhanced Raman scattering II: concluding remarks. Faraday Discuss. 2017, 205, 601– 613, DOI: 10.1039/C7FD00206HGoogle Scholar519Surface-enhanced Raman scattering II: concluding remarksPorter, Marc D.; Granger, Jennifer H.Faraday Discussions (2017), 205 (Surface Enhanced Raman Scattering--SERS), 601-613CODEN: FDISE6; ISSN:1359-6640. (Royal Society of Chemistry)Surface-enhanced Raman scattering (SERS) enables the detection of a large no. of different adsorbates at extraordinarily low levels. This plasmonics-based technol. has undergone a no. of remarkable advances since its discovery over 40 years ago, and has emerged from being an investigative tool confined largely to the research lab. into a much more usable tool across a broad range of investigative studies, both within the lab. and beyond. The purpose of this Concluding remarks manuscript is to capture, at least in part, the developments in this area since the first Faraday discussion of SERS over a decade ago. It begins with a brief contextual overview and then moves into describing a few of the many highlights from the meeting. Along the way, we have added a few comments and perspectives as a means to more fully stage where the different areas of research with SERS stand today. An addendum is included that collects a few of the recent perspectives on the original work and activities in this area.
- 520De Silva Indrasekara, A. S.; Johnson, S. F.; Odion, R. A.; Vo-Dinh, T. Manipulation of the Geometry and Modulation of the Optical Response of Surfactant-Free Gold Nanostars: A Systematic Bottom-Up Synthesis. ACS Omega 2018, 3, 2202– 2210, DOI: 10.1021/acsomega.7b01700Google Scholar520Manipulation of the Geometry and Modulation of the Optical Response of Surfactant-Free Gold Nanostars: A Systematic Bottom-Up SynthesisDe Silva Indrasekara, Agampodi S.; Johnson, Sean F.; Odion, Ren A.; Vo-Dinh, TuanACS Omega (2018), 3 (2), 2202-2210CODEN: ACSODF; ISSN:2470-1343. (American Chemical Society)The optimization of the bottom-up synthesis that improves the reproducibility and homogeneity of Au-branched nanoparticles and the modulation of their morphol., particularly the branch d., geometrical features of the branches to obtain the desired optical properties. is presented. The order of reagent addn. is crucial for improved homogeneity of the branched nature of nanoparticles that enable a high batch-batch reproducibility and reliability. A different combination of the synthesis parameters, in particular, additive halides and concn. ratios of reactive Au to Ag and Au to Au seeds, which yield branched nanoparticle of similar localized surface plasmon resonances but with distinguishable changes in the dimensions of the branches, was realized. The study introduces the design parameters for the purpose-tailored manufg. of surfactant-free Au nanostars in a reliable manner.
- 521Song, T.; Gao, F.; Guo, S.; Zhang, Y.; Li, S.; You, H.; Du, Y. A review of the role and mechanism of surfactants in the morphology control of metal nanoparticles. Nanoscale 2021, 13, 3895– 3910, DOI: 10.1039/D0NR07339CGoogle Scholar521A review of the role and mechanism of surfactants in the morphology control of metal nanoparticlesSong, Tongxin; Gao, Fei; Guo, Siyu; Zhang, Yangping; Li, Shujin; You, Huaming; Du, YukouNanoscale (2021), 13 (7), 3895-3910CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)A review. Although great progress has been made in the synthesis of metal nanoparticles, good repeatability and accurate predictability are still difficult to achieve. This difficulty can be attributed to the synthetic method based primarily on observation and subjective experience, and the role of many surfactants remains unclear. It should be noted that surfactants play an important role in the synthetic process. Understanding their function and mechanism in the synthetic process is a prerequisite for the rational design of nanocatalysts with ideal morphol. and performance. In this review article, the function of surfactants is introduced first, and then the mechanism of action of surfactants in controlling the morphol. of nanoparticles is discussed according to the types of surfactants, and the promoting and sealing effects of surfactants on the crystal surface is revealed. The relationship between surfactants and the morphol. structure of nanoparticles is studied. The removal methods of surfactants are discussed, and the existing problems in the current development strategy are summarized. Finally, the application of surfactants in controlling the morphol. of metal nanocrystals is prospected. It is hoped that the review can open up new avenues for the synthesis of nanocrystals.
- 522Hossain, M. K. Nanoassembly of gold nanoparticles: An active substrate for size-dependent surface-enhanced Raman scattering. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 2020, 242, 118759, DOI: 10.1016/j.saa.2020.118759Google ScholarThere is no corresponding record for this reference.
- 523Zhou, H.; Zhang, J.; Li, B.; Liu, J.; Xu, J.-J.; Chen, H.-Y. Dual-Mode SERS and Electrochemical Detection of miRNA Based on Popcorn-like Gold Nanofilms and Toehold-Mediated Strand Displacement Amplification Reaction. Anal. Chem. 2021, 93, 6120– 6127, DOI: 10.1021/acs.analchem.0c05221Google Scholar523Dual-Mode SERS and Electrochemical Detection of miRNA Based on Popcorn-like Gold Nanofilms and Toehold-Mediated Strand Displacement Amplification ReactionZhou, Hong; Zhang, Jishou; Li, Binxiao; Liu, Jing; Xu, Jing-Juan; Chen, Hong-YuanAnalytical Chemistry (Washington, DC, United States) (2021), 93 (15), 6120-6127CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)MicroRNA (miRNA) has emerged as one of the ideal target biomarker analytes for cancer detection because its abnormal expression is closely related to the occurrence of many cancers. In this work, we combined three-dimensional (3D) popcorn-like gold nanofilms as novel surface-enhanced Raman scattering (SERS)-electrochem. active substrates with toehold-mediated strand displacement reactions (TSDRs) to construct a DNA mol. machine for SERS-electrochem. dual-mode detection of miRNA. 3D popcorn-like spatial structures generated more active "hot spots" and thus enhanced the sensitivity of SERS and electrochem. signals. Besides, the TSDRs showed high sequence-dependence and high specificity. The addn. of target miRNA will trigger the mol. machine to perform two TSDRs in the presence of signal DNA strands modified by R6G (R6G-DNA), thus achieving an enzyme-free amplification detection of miRNA with a low limit of detection of 0.12 fM (for the SERS method) and 2.2 fM (for the electrochem. method). This biosensor can also serve as a universally amplified and sensitive detection platform for monitoring different biomarkers, such as cancer-related DNA, mRNA, or miRNA mols., with high selectivity by changing the corresponding probe sequence.
- 524Cortese, M.; Gigliobianco, M. R.; Magnoni, F.; Censi, R.; Di Martino, P. Compensate for or Minimize Matrix Effects? Strategies for Overcoming Matrix Effects in Liquid Chromatography-Mass Spectrometry Technique: A Tutorial Review. Molecules 2020, 25, 3047, DOI: 10.3390/molecules25133047Google Scholar524Compensate for or minimize matrix effects? Strategies for overcoming matrix effects in liquid chromatography-mass spectrometry technique: a tutorial reviewCortese, Manuela; Gigliobianco, Maria Rosa; Magnoni, Federico; Censi, Roberta; Di Martino, PieraMolecules (2020), 25 (13), 3047CODEN: MOLEFW; ISSN:1420-3049. (MDPI AG)A review. In recent decades, mass spectrometry techniques, particularly when combined with sepn. methods such as high-performance liq. chromatog., have become increasingly important in pharmaceutical, bio-anal., environmental, and food science applications because they afford high selectivity and sensitivity. However, mass spectrometry has limitations due to the matrix effects (ME), which can be particularly marked in complex mixes, when the analyte co-elutes together with other mols., altering anal. results quant. This may be detrimental during method validation, neg. affecting reproducibility, linearity, selectivity, accuracy, and sensitivity. Starting from literature and own experience, this review intends to provide a simple guideline for selecting the best operative conditions to overcome matrix effects in LC-MS techniques, to obtain the best result in the shortest time. The proposed methodol. can be of benefit in different sectors, such as pharmaceutical, bio-anal., environmental, and food sciences. Depending on the required sensitivity, analysts may minimize or compensate for ME. When sensitivity is crucial, anal. must try to minimize ME by adjusting MS parameters, chromatog. conditions, or optimizing clean-up. On the contrary, to compensate for ME analysts should have recourse to calibration approaches depending on the availability of blank matrix. When blank matrixes are available, calibration can occur through isotope labeled internal stds. and matrix matched calibration stds. conversely, when blank matrixes are not available, calibration can be performed through isotope labeled internal stds., background subtraction, or surrogate matrixes. In any case, an adjusting of MS parameters, chromatog. conditions, or a clean-up are necessary.
- 525Zhang, D.; Xie, Y.; Deb, S. K.; Davison, V. J.; Ben-Amotz, D. Isotope Edited Internal Standard Method for Quantitative Surface-Enhanced Raman Spectroscopy. Anal. Chem. 2005, 77, 3563– 3569, DOI: 10.1021/ac050338hGoogle Scholar525Isotope Edited Internal Standard Method for Quantitative Surface-Enhanced Raman SpectroscopyZhang, Dongmao; Xie, Yong; Deb, Shirshendu K.; Davison, V. Jo; Ben-Amotz, DorAnalytical Chemistry (2005), 77 (11), 3563-3569CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)A new isotope edited internal std. (IEIS) method for quant. surface-enhanced Raman spectroscopy (SERS) is demonstrated using rhodamine 6G (R6G-d0) and rhodamine 6G (R6G-d4) edited with deuterium. The reproducibility and accuracy of the IEIS method is investigated both under optical resonance (SERRS) and nonresonance (SERS) conditions. A batch-to-batch concn. measurement reproducibility of better than 3% is demonstrated over a concn. range of 200 pM-2 μM with up to a factor of 3 difference between the concn. of the analyte and its IEIS. The superior performance of the IEIS method is further illustrated by comparing results obtained using abs. SERS/SERRS intensity calibration (with no internal std.) or using adenine (rather than R6G-d4) as an internal std. for R6G concn. quantization. Potential biomedical gene expression and comparative proteomic applications of the IEIS method are discussed.
- 526Zong, C.; Xu, M.; Xu, L.-J.; Wei, T.; Ma, X.; Zheng, X.-S.; Hu, R.; Ren, B. Surface-Enhanced Raman Spectroscopy for Bioanalysis: Reliability and Challenges. Chem. Rev. 2018, 118, 4946– 4980, DOI: 10.1021/acs.chemrev.7b00668Google Scholar526Surface-Enhanced Raman Spectroscopy for Bioanalysis: Reliability and ChallengesZong, Cheng; Xu, Mengxi; Xu, Li-Jia; Wei, Ting; Ma, Xin; Zheng, Xiao-Shan; Hu, Ren; Ren, BinChemical Reviews (Washington, DC, United States) (2018), 118 (10), 4946-4980CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review. Surface-enhanced Raman spectroscopy (SERS) inherits the rich chem. fingerprint information on Raman spectroscopy and gains sensitivity by plasmon-enhanced excitation and scattering. In particular, most Raman peaks have a narrow width suitable for multiplex anal., and the measurements can be conveniently made under ambient and aq. conditions. These merits make SERS a very promising technique for studying complex biol. systems, and SERS has attracted increasing interest in biorelated anal. However, there are still great challenges that need to be addressed until it can be widely accepted by the biorelated communities, answer interesting biol. questions, and solve fatal clin. problems. SERS applications in bioanal. involve the complex interactions of plasmonic nanomaterials with biol. systems and their environments. The reliability becomes the key issue of bioanal. SERS to ext. meaningful information from SERS data. This review provides a comprehensive overview of bioanal. SERS with the main focus on the reliability issue. The authors first introduce the mechanism of SERS to guide the design of reliable SERS expts. with high detection sensitivity. The authors then introduce the current understanding of the interaction of nanomaterials with biol. systems, mainly living cells, to guide the design of functionalized SERS nanoparticles for target detection. The authors further introduce the current status of label-free (direct) and labeled (indirect) SERS detections, for systems from biomols., to pathogens, to living cells, and the potential interferences from exptl. design, measurement conditions, and data anal are discussed. In the end, the authors give an outlook of the key challenges in bioanal. SERS, including reproducibility, sensitivity, and spatial and time resoln.
- 527Deb, S. K.; Davis, B.; Ben-Amotz, D.; Davisson, V. J. Accurate Concentration Measurements Using Surface-Enhanced Raman and Deuterium Exchanged Dye Pairs. Appl. Spectrosc. 2008, 62, 1001– 1007, DOI: 10.1366/000370208785793290Google Scholar527Accurate concentration measurements using surface-enhanced Raman and deuterium exchanged dye pairsDeb, Shirshendu K.; Davis, Brandon; Ben-Amotz, Dor; Davisson, V. JoApplied Spectroscopy (2008), 62 (9), 1001-1007CODEN: APSPA4; ISSN:0003-7028. (Society for Applied Spectroscopy)Quant. applications of surface-enhanced resonance Raman scattering (SERRS) are often limited by the reproducibility of SERRS intensities, given the difficulty of controlling analyte-substrate interactions and the assocd. local field enhancement. As demonstrated here, SERRS from dye mols. even within the same structural class that compete with similar substrates display distinct spectral intensities that are not proportional to analyte concns., which limits their use as internal standardization probes and/or for multiplex anal. Recently, we demonstrated that isotopic variants of rhodamine 6G (R6G), namely R6G-d0 and R6G-d4, can be used for internal stds. in SERRS expts. with a linear optical response from picomolar to micromolar concns. (of total analytes). Here we extend these results by describing a straightforward method for obtaining isotopomeric pairs of other Raman active dyes by hydrogen-deuterium exchange conditions for substitution at electron-rich arom. heterocycles. Most of the known SERRS active probes can be converted into the corresponding isotopomeric mol. by this exchange method, which significantly expands the scope of the isotopic edited internal std. (IEIS) approach. The relative quantification using IEIS enables accurate, reproducible (residual std. deviation ±2.2%) concn. measurements over a range of 200 pM to 2 μM. These studies enable easy access to a variety of isotopically substituted Raman active dyes and establish the generality of the methodol. for quant. SERRS measurements. For the first time, three rhodamine 6G isotopomers have been created and show distinct Raman spectra, demonstrating the principle of the approach for application as a multiplex technique in biomol. detection/quantification.
- 528Yin, P.-G.; Jiang, L.; Lang, X.-F.; Guo, L.; Yang, S. Quantitative analysis of mononucleotides by isotopic labeling surface-enhanced Raman scattering spectroscopy. Biosens. Bioelectron. 2011, 26, 4828– 4831, DOI: 10.1016/j.bios.2011.05.042Google ScholarThere is no corresponding record for this reference.
- 529Subaihi, A.; Xu, Y.; Muhamadali, H.; Mutter, S. T.; Blanch, E. W.; Ellis, D. I.; Goodacre, R. Towards improved quantitative analysis using surface-enhanced Raman scattering incorporating internal isotope labelling. Analytical Methods 2017, 9, 6636– 6644, DOI: 10.1039/C7AY02527KGoogle ScholarThere is no corresponding record for this reference.
- 530Qin, L.; Zhang, X.; Wu, J.; Zhang, W.; Lu, X.; Sun, H.; Zhang, J.; Guo, L.; Xie, J. Quantification and toxicokinetics of paraquat in mouse plasma and lung tissues by internal standard surface-enhanced Raman spectroscopy. Anal. Bioanal. Chem. 2022, 414, 2371– 2383, DOI: 10.1007/s00216-022-03875-1Google ScholarThere is no corresponding record for this reference.
- 531Guo, P.; Zeng, W.; Tian, S.; Chen, H.; Liu, W.; Chen, C. Quantitative detection of nanomolar drug using surface-enhanced Raman scattering combined with internal standard method and two-step centrifugation method. Microchemical Journal 2020, 158, 105202, DOI: 10.1016/j.microc.2020.105202Google ScholarThere is no corresponding record for this reference.
- 532Wu, Y.; Liu, J.; Xu, R.; Li, J.; Fu, C.; Shi, W.; Chen, J. Recent advances in ratiometric surface-enhanced Raman spectroscopy sensing strategies. Microchemical Journal 2024, 199, 110127, DOI: 10.1016/j.microc.2024.110127Google ScholarThere is no corresponding record for this reference.
- 533Wei, W.; Hassan, M. M.; Wu, J.; Mu, X.; Li, H.; Chen, Q. Competitive Ratiometric Aptasensing with Core-Internal Standard-Shell Structure Based on Surface-Enhanced Raman Scattering. J. Agric. Food Chem. 2023, 71, 857– 866, DOI: 10.1021/acs.jafc.2c06850Google ScholarThere is no corresponding record for this reference.
- 534Jiang, X.; Tan, Z.; Lin, L.; He, J.; He, C.; Thackray, B. D.; Zhang, Y.; Ye, J. Surface-Enhanced Raman Nanoprobes with Embedded Standards for Quantitative Cholesterol Detection. Small Methods 2018, 2, 1800182, DOI: 10.1002/smtd.201800182Google ScholarThere is no corresponding record for this reference.
- 535Li, M.; Wang, J.-Y.; Chen, Q.-Q.; Lin, L.-H.; Radjenovic, P.; Zhang, H.; Luo, S.-Y.; Tian, Z.-Q.; Li, J.-F. Background-Free Quantitative Surface Enhanced Raman Spectroscopy Analysis Using Core–Shell Nanoparticles with an Inherent Internal Standard. Anal. Chem. 2019, 91, 15025– 15031, DOI: 10.1021/acs.analchem.9b03703Google Scholar535Background-Free Quantitative Surface Enhanced Raman Spectroscopy Analysis Using Core-Shell Nanoparticles with an Inherent Internal StandardLi, Mei; Wang, Jing-Yu; Chen, Qing-Qi; Lin, Long-Hui; Radjenovic, Petar; Zhang, Hua; Luo, Shi-Yi; Tian, Zhong-Qun; Li, Jian-FengAnalytical Chemistry (Washington, DC, United States) (2019), 91 (23), 15025-15031CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Surface enhanced Raman spectroscopy (SERS) is an ultrasensitive label-free anal. technique that can provide unique chem. and structural fingerprint information. However, gaining reliable quant. anal. with SERS remains a huge challenge because of poor reproducibility and the instability of nanostructured SERS active surfaces. Herein, an effective strategy of coating Au nanoparticles (NPs) with ultra-thin and uniform Prussian blue (PB) shell (Au@PB NPs) was developed for quant. detection of dopamine (DA) concns. in blood serum and crystal violet (CV) contaminants in lake water. The only intense PB Raman signal at 2155 cm-1 served as an ideal and interference-free internal std. (IS) for correcting fluctuations in the Raman intensities of analytes. Also, the stability of Au@PB NPs was investigated, exhibiting good functionality in strong acid solns. and thermal stability at 100°. This work demonstrates a convenient and fast quant. SERS technique for detecting analyte concns. in complex systems and has a great no. of potential applications for use in anal. chem.
- 536Mei, R.; Wang, Y.; Shi, S.; Zhao, X.; Zhang, Z.; Wang, X.; Shen, D.; Kang, Q.; Chen, L. Highly Sensitive and Reliable Internal-Standard Surface-Enhanced Raman Scattering Microneedles for Determination of Bacterial Metabolites as Infection Biomarkers in Skin Interstitial Fluid. Anal. Chem. 2022, 94, 16069– 16078, DOI: 10.1021/acs.analchem.2c03208Google Scholar536Highly Sensitive and Reliable Internal-Standard Surface-Enhanced Raman Scattering Microneedles for Determination of Bacterial Metabolites as Infection Biomarkers in Skin Interstitial FluidMei, Rongchao; Wang, Yunqing; Shi, Shang; Zhao, Xizhen; Zhang, Zhiyang; Wang, Xiaoyan; Shen, Dazhong; Kang, Qi; Chen, LingxinAnalytical Chemistry (Washington, DC, United States) (2022), 94 (46), 16069-16078CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Microneedles (MNs) are currently one of the most promising tools for skin interstitial fluid (ISF)-based biosensing, while it is still a challenge to expand the detectable biomarkers in ISF due to limited MNs types and detection techniques. Herein, highly sensitive internal-std. surface-enhanced Raman scattering microneedles (IS-SERS-MNs) were developed, which enabled the reliable detection of bacterial metabolites in ISF as new detectable biomarkers for infection diagnosis. The developed IS-SERS-MNs can not only directly detect pyocyanin (a representative bacterial metabolite) present in mouse dermal ISF but also indirectly detect pyocyanin in the hypodermis via its diffusion into the dermis, revealing a new possible pathway for the source of biomarkers in dermal ISF. Moreover, the SERS signal of pyocyanin was also clearly detected at real mouse wounds, indicating that the developed IS-SERS-MNs have great potential in minimally invasive and painless diagnosis of bacterial infection via a new ISF route. This work not only develops IS-SERS-MNs as a powerful tool for expanding the application of SERS-based MNs but also provides a new chance for ISF-related infection diagnosis.
- 537Zou, Y.; Chen, L.; Song, Z.; Ding, D.; Chen, Y.; Xu, Y.; Wang, S.; Lai, X.; Zhang, Y.; Sun, Y.; Chen, Z.; Tan, W. Stable and unique graphitic Raman internal standard nanocapsules for surface-enhanced Raman spectroscopy quantitative analysis. Nano Research 2016, 9, 1418– 1425, DOI: 10.1007/s12274-016-1037-6Google ScholarThere is no corresponding record for this reference.
- 538Tian, H.; Zhang, N.; Tong, L.; Zhang, J. In Situ Quantitative Graphene-Based Surface-Enhanced Raman Spectroscopy. Small Methods 2017, 1, 1700126, DOI: 10.1002/smtd.201700126Google ScholarThere is no corresponding record for this reference.
- 539Gao, J.; Zhao, C.; Zhang, Z.; Li, G. An intrinsic internal standard substrate of Au@PS-b-P4VP for rapid quantification by surface enhanced Raman scattering. Analyst 2017, 142, 2936– 2944, DOI: 10.1039/C7AN01061CGoogle Scholar539An intrinsic internal standard substrate of Au@PS-b-P4VP for rapid quantification by surface enhanced Raman scatteringGao, Jiamin; Zhao, Cheng; Zhang, Zhuomin; Li, GongkeAnalyst (Cambridge, United Kingdom) (2017), 142 (16), 2936-2944CODEN: ANALAO; ISSN:0003-2654. (Royal Society of Chemistry)Reliable quantification by surface enhanced Raman scattering (SERS) highly depends on the development of a reproducible substrate with excellent anti-interference capability. In this work, an intrinsic internal std. (IS) SERS substrate based on a diblock copolymer, polystyrene-block-poly-4-vinylpyridine (PS-b-P4VP), as a template was developed by a modified block copolymer lithog. (BCL) technique of reserving the diblock copolymer template. This substrate generated a stable vibration peak at 1066 cm-1 attributed to poly(4-vinylpyridine) (P4VP) which could be used as an intrinsic IS for precise SERS quantification. A series of characterization results showed that the diblock copolymer template endowed this substrate with homogeneous distribution of Au nanoparticles, excellent stability and reproducibility. A minor relative std. deviation (RSDs) of SERS responses at 1066 cm-1 was measured and calcd. to be 4.3% from ten different substrates in the same batch, which suggested good substrate-to-substrate reproducibility of this substrate. Finally, this intrinsic IS substrate was successfully applied for the rapid quantification of a trace banned dye, chrysoidine, in food samples with complicated matrixes by SERS. It was proved that chrysoidine could be found and quantified to be 0.50 and 0.41 mg L-1 in a pos. dried bean curd stick and chilli powder sample resp. with good recoveries by this substrate coupled with SERS. The development of intrinsic IS substrates would benefit rapid and accurate quantification of trace targets in complex samples coupled with SERS anal.
- 540Ameer, F. S.; Hu, W.; Ansar, S. M.; Siriwardana, K.; Collier, W. E.; Zou, S.; Zhang, D. Robust and Reproducible Quantification of SERS Enhancement Factors Using a Combination of Time-Resolved Raman Spectroscopy and Solvent Internal Reference Method. J. Phys. Chem. C 2013, 117, 3483– 3488, DOI: 10.1021/jp311752mGoogle Scholar540Robust and Reproducible Quantification of SERS Enhancement Factors Using a Combination of Time-Resolved Raman Spectroscopy and Solvent Internal Reference MethodAmeer, Fathima S.; Hu, Wenfang; Ansar, Siyam M.; Siriwardana, Kumudu; Collier, Willard E.; Zou, Shengli; Zhang, DongmaoJournal of Physical Chemistry C (2013), 117 (7), 3483-3488CODEN: JPCCCK; ISSN:1932-7447. (American Chemical Society)Recent research has demonstrated that the nanoparticle (NP) surface enhanced Raman spectroscopy (SERS) substrate modifies an analyte's Raman signal through two competitive mechanisms, SERS enhancement and NP inner filter effect, instead of SERS enhancement alone as commonly believed. Using a combination of time-resolved Raman spectroscopy and a solvent internal ref. method, reported herein is a quant. detn. of the SERS enhancement factors (EFs) of mercaptobenzimidazole (MBI), a model organothiol, adsorbed onto gold and silver nanoparticles (AuNPs and AgNPs). The peak MBI SERS EF depends only on the type and size of NPs, but not analyte and NP concns., or the type (KF, KCl, KBr, and K2SO4) and concns. of the electrolytic aggregation agents. The exptl. SERS EFs of MBI on both AuNPs and AgNPs can be fully explained by the electromagnetic mechanism alone. This result, combined with our recent findings that a series of structurally diverse organothiols have similar SERS EFs, argues quite strongly against the possibility of large chem. enhancement (e.g., >10 times) for organothiols adsorbed onto colloidal AuNPs and AgNPs.
- 541Yu, F.; Su, M.; Tian, L.; Wang, H.; Liu, H. Organic Solvent as Internal Standards for Quantitative and High-Throughput Liquid Interfacial SERS Analysis in Complex Media. Anal. Chem. 2018, 90, 5232– 5238, DOI: 10.1021/acs.analchem.8b00008Google Scholar541Organic Solvent as Internal Standards for Quantitative and High-Throughput Liquid Interfacial SERS Analysis in Complex MediaYu, Fanfan; Su, Mengke; Tian, Li; Wang, Hongyan; Liu, HonglinAnalytical Chemistry (Washington, DC, United States) (2018), 90 (8), 5232-5238CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Liq.-state interfacial nanoparticle arrays for surface-enhanced Raman scattering (SERS) promises a practical, substrate-free, and rapid anal. but faces a great challenge to develop a batch and uniform fabrication strategy with stable internal stds. (IS) because of the difficulties in precisely locating both the IS tags and analytes in the same local structure under the harsh conditions of biphasic liq. interface. Here, the authors develop a fast batch prepn. of self-ordered dense Au nanoparticle (GNP) arrays on cyclohexane/water biphasic interface in 96-well plates with the assist of acetone as the phase-crossing inducer. The acetone can ext. the pesticide mols. via a simple dipping sample peels and can rapidly capture and locate the pesticide mol. into the plasmonic hotspots. Meanwhile, this phase-crossing solvent, acetone itself, generates stable SERS signal and was used as the IS tags to calibrate the signal fluctuation. This platform presents an excellent uniformity with a relative std. deviation of 5.9% compared to the relative std. deviation of 14.5% without the IS's correction and a good sensitivity with a limit of detection (LOD) of 1 nM thiram. This high-throughput strategy for analyzing pesticide residues at fruit peels reached detection levels of nanograms per square centimeter (ng/cm2). Combined with the 96-well plates, this platform greatly facilitates the self-assembly and multiplex sampling. The self-ordered arrays at two immiscible phases interface evidenced the detection of both the oil-sol. thiabendazole and the water-sol. thiram mols. and also realized the multiplex and two-phase detection of these two pesticides. This platform offers vast possibilities for on-site sensing of various analytes and paves a new way for the quant. and high-throughput SERS analyzer just as convenient as the microplate reader.
- 542Li, D.; Zhang, Z.; Wang, X.; Wang, Y.; Gao, X.; Li, Y. A direct method for detecting proteins in body fluids by Surface-Enhanced Raman Spectroscopy under native conditions. Biosens. Bioelectron. 2022, 200, 113907, DOI: 10.1016/j.bios.2021.113907Google Scholar542A direct method for detecting proteins in body fluids by Surface-Enhanced Raman Spectroscopy under native conditionsLi, Dan; Zhang, Zhe; Wang, Xiaotong; Wang, Yunpeng; Gao, Xin; Li, YangBiosensors & Bioelectronics (2022), 200 (), 113907CODEN: BBIOE4; ISSN:0956-5663. (Elsevier B.V.)Surface enhanced Raman spectroscopy (SERS) is widely used in biomol. detection. However, maintaining the native structure of proteins while obtaining sensitive and reproducible SERS signals of unlabeled proteins remains a challenge. In this study, dichloromethane (DCM) and CaCl2 were used to optimize the aggregation of Ag nanoparticles (AgNPs), and several proteins were analyzed comprehensively. Calcium ions removed citrate ions outside AgNPs, inducing hot spots and achieving high-sensitivity SERS signals of proteins. Furthermore, 20 random samples of 0.5μg/mL Hb were analyzed by this method. The obtained spectra showed good repeatability and a high quality. Using the peak intensity of DCM as internal parameter, the differences in peak intensities at the same position were analyzed to distinguish different proteins and evaluate changes in protein structure. Subsequently, the protein content in protein mixts. and serum was quantified and a good linear relationship between peak intensity and protein concn. was obtained. This method shows great promise in the fields of food testing and clin. diagnosis.
- 543Nam, W.; Zhao, Y.; Song, J.; Ali Safiabadi Tali, S.; Kang, S.; Zhu, W.; Lezec, H. J.; Agrawal, A.; Vikesland, P. J.; Zhou, W. Plasmonic Electronic Raman Scattering as Internal Standard for Spatial and Temporal Calibration in Quantitative Surface-Enhanced Raman Spectroscopy. J. Phys. Chem. Lett. 2020, 11, 9543– 9551, DOI: 10.1021/acs.jpclett.0c03056Google Scholar543Plasmonic Electronic Raman Scattering as Internal Standard for Spatial and Temporal Calibration in Quantitative Surface-Enhanced Raman SpectroscopyNam, Wonil; Zhao, Yuming; Song, Junyeob; Ali Safiabadi Tali, Seied; Kang, Seju; Zhu, Wenqi; Lezec, Henri J.; Agrawal, Amit; Vikesland, Peter J.; Zhou, WeiJournal of Physical Chemistry Letters (2020), 11 (22), 9543-9551CODEN: JPCLCD; ISSN:1948-7185. (American Chemical Society)Ultrasensitive surface-enhanced Raman spectroscopy (SERS) still faces difficulties in quant. anal. because of its susceptibility to local optical field variations at plasmonic hotspots in metallo-dielec. nanostructures. Current SERS calibration approaches using Raman tags have inherent limitations due to spatial occupation competition with analyte mols., spectral interference with analyte Raman peaks, and photodegrdn. Herein, we report that plasmon-enhanced electronic Raman scattering (ERS) signals from metal can serve as an internal std. for spatial and temporal calibration of mol. Raman scattering (MRS) signals from analyte mols. at the same hotspots, enabling rigorous quant. SERS anal. We observe a linear dependence between ERS and MRS signal intensities upon spatial and temporal variations of excitation optical fields, manifesting the |E|4 enhancements for both ERS and MRS processes at the same hotspots in agreement with our theor. prediction. Furthermore, we find that the ERS calibration's performance limit can result from orientation variations of analyte mols. at hotspots.
- 544Kiefl, E. J.; Kiefl, R. F.; dos Santos, D. P.; Brolo, A. G. Evaluation of Surface-Enhanced Raman Spectroscopy Substrates from Single-Molecule Statistics. J. Phys. Chem. C 2017, 121, 25487– 25493, DOI: 10.1021/acs.jpcc.7b08691Google Scholar544Evaluation of Surface-Enhanced Raman Spectroscopy Substrates from Single-Molecule StatisticsKiefl, Evan J.; Kiefl, Robert F.; dos Santos, Diego P.; Brolo, Alexandre G.Journal of Physical Chemistry C (2017), 121 (45), 25487-25493CODEN: JPCCCK; ISSN:1932-7447. (American Chemical Society)Accurate quantification of substrate characteristics is a central pursuit within the field of surface-enhanced Raman spectroscopy (SERS). A theory based on single-mol. SERS (SM-SERS) statistics was developed for comprehensive substrate evaluation. This approach is applicable to general substrates possessing many hotspots and is capable of quantifying hotspot strength variation using a min. set of fitting parameters. The model was validated for simulated substrates and then applied to the SM-SERS statistics of a roughened Ag electrode, for which the degree of hotspot uniformity was quantified. The fitted model parameters provide important information concerning the structure-activity relation of hotspots and can be used to directly compare SERS substrates. Overall, the results present an exptl. determinable parameter set that potentially improves upon the widely used av. enhancement factor metric currently used for SERS substrate evaluation.
- 545Fukunaga, Y.; Okada, T. Quantification using statistical parameters derived from signal intensity distributions in surface enhanced Raman scattering (SERS). Anal. Chim. Acta 2021, 1181, 338931, DOI: 10.1016/j.aca.2021.338931Google Scholar545Quantification using statistical parameters derived from signal intensity distributions in surface enhanced Raman scattering (SERS)Fukunaga, Yu; Okada, TetsuoAnalytica Chimica Acta (2021), 1181 (), 338931CODEN: ACACAM; ISSN:0003-2670. (Elsevier B.V.)Raman spectroscopy is a powerful method, which provides information on mol. structures, conformations, interactions etc. However, its applications are severely restricted because of low sensitivity. Although surface enhanced Raman scattering (SERS) significantly enhances sensitivity and enables single-mol. detection, quantification by this method is still challenging because of large signal fluctuations. In the present study, the signal intensity distributions (SIDs) in SERS of adenine and thymine on the silver nanoparticle (AgNP) platform are analyzed based on more than 10000 spectra to pursue the possibility of SERS quantification. The signals always involve large fluctuations but show statistically relevant patterns. SIDs are well represented by the exponentially modified Gaussian function, which is characterized by reproducible parameters. Thus, robust quantification is feasible using the parameters derived from the SIDs. At least 200 spectra for a given concn. are necessary to derive reproducible parameter values from the SID. The mean signal intensity detd. from the SIDs is proportional to the adenine concn. in the range of 10-75 μM. However, this parameter becomes independent of the adenine concn. in the lower concn. range. In such concns., minor events, which give distinct SERS spectra, occasionally occur but have only marginal impacts on the mean signal intensity. The cor. std. deviation of the SID, which is estd. from the complementary error function, well represents the minor events and provides a clear correlation with the concn. in the range of 0.5-7.5 μM. Furthermore, the quantification in the nanomolar range is made possible by the incorporation of sample freezing, which enables to enrich target analytes and AgNPs in a liq. phase confined by ice.
- 546Brulé, T.; Bouhelier, A.; Yockell-Lelièvre, H.; Clément, J.-E.; Leray, A.; Dereux, A.; Finot, E. Statistical and Fourier Analysis for In-line Concentration Sensitivity in Single Molecule Dynamic-SERS. ACS Photonics 2015, 2, 1266– 1271, DOI: 10.1021/acsphotonics.5b00134Google ScholarThere is no corresponding record for this reference.
- 547Fornasaro, S.; Alsamad, F.; Baia, M.; Batista de Carvalho, L. A. E.; Beleites, C.; Byrne, H. J.; Chiadò, A.; Chis, M.; Chisanga, M.; Daniel, A.; Dybas, J.; Eppe, G.; Falgayrac, G.; Faulds, K.; Gebavi, H.; Giorgis, F.; Goodacre, R.; Graham, D.; La Manna, P.; Laing, S.; Litti, L.; Lyng, F. M.; Malek, K.; Malherbe, C.; Marques, M. P. M.; Meneghetti, M.; Mitri, E.; Mohaček-Grošev, V.; Morasso, C.; Muhamadali, H.; Musto, P.; Novara, C.; Pannico, M.; Penel, G.; Piot, O.; Rindzevicius, T.; Rusu, E. A.; Schmidt, M. S.; Sergo, V.; Sockalingum, G. D.; Untereiner, V.; Vanna, R.; Wiercigroch, E.; Bonifacio, A. Surface Enhanced Raman Spectroscopy for Quantitative Analysis: Results of a Large-Scale European Multi-Instrument Interlaboratory Study. Anal. Chem. 2020, 92, 4053– 4064, DOI: 10.1021/acs.analchem.9b05658Google Scholar547Surface Enhanced Raman Spectroscopy for Quantitative Analysis: Results of a Large-Scale European Multi-Instrument Interlaboratory StudyFornasaro, Stefano; Alsamad, Fatima; Baia, Monica; Batista de Carvalho, Luis A. E.; Beleites, Claudia; Byrne, Hugh J.; Chiado, Alessandro; Chis, Mihaela; Chisanga, Malama; Daniel, Amuthachelvi; Dybas, Jakub; Eppe, Gauthier; Falgayrac, Guillaume; Faulds, Karen; Gebavi, Hrvoje; Giorgis, Fabrizio; Goodacre, Royston; Graham, Duncan; La Manna, Pietro; Laing, Stacey; Litti, Lucio; Lyng, Fiona M.; Malek, Kamilla; Malherbe, Cedric; Marques, Maria P. M.; Meneghetti, Moreno; Mitri, Elisa; Mohacek-Grosev, Vlasta; Morasso, Carlo; Muhamadali, Howbeer; Musto, Pellegrino; Novara, Chiara; Pannico, Marianna; Penel, Guillaume; Piot, Olivier; Rindzevicius, Tomas; Rusu, Elena A.; Schmidt, Michael S.; Sergo, Valter; Sockalingum, Ganesh D.; Untereiner, Valerie; Vanna, Renzo; Wiercigroch, Ewelina; Bonifacio, AloisAnalytical Chemistry (Washington, DC, United States) (2020), 92 (5), 4053-4064CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Surface-enhanced Raman scattering (SERS) is a powerful and sensitive technique for the detection of fingerprint signals of mols. and for the investigation of a series of surface chem. reactions. Many studies introduced quant. applications of SERS in various fields, and several SERS methods have been implemented for each specific application, ranging in performance characteristics, analytes used, instruments, and anal. matrixes. In general, very few methods have been validated according to international guidelines. As a consequence, the application of SERS in highly regulated environments is still considered risky, and the perception of a poorly reproducible and insufficiently robust anal. technique has persistently retarded its routine implementation. Collaborative trials are a type of interlab. study (ILS) frequently performed to ascertain the quality of a single anal. method. The idea of an ILS of quantification with SERS arose within the framework of Working Group 1 (WG1) of the EU COST Action BM1401 Raman4Clinics in an effort to overcome the problematic perception of quant. SERS methods. Here, we report the first interlab. SERS study ever conducted, involving 15 labs. and 44 researchers. In this study, we tried to define a methodol. to assess the reproducibility and trueness of a quant. SERS method and to compare different methods. In our opinion, this is a first important step toward a "standardization" process of SERS protocols, not proposed by a single lab. but by a larger community.
- 548de Albuquerque, C. D. L.; Sobral-Filho, R. G.; Poppi, R. J.; Brolo, A. G. Digital Protocol for Chemical Analysis at Ultralow Concentrations by Surface-Enhanced Raman Scattering. Anal. Chem. 2018, 90, 1248– 1254, DOI: 10.1021/acs.analchem.7b03968Google Scholar548Digital Protocol for Chemical Analysis at Ultralow Concentrations by Surface-Enhanced Raman Scatteringde Albuquerque, Carlos Diego L.; Sobral-Filho, Regivaldo G.; Poppi, Ronei J.; Brolo, Alexandre G.Analytical Chemistry (Washington, DC, United States) (2018), 90 (2), 1248-1254CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Single mol. surface-enhanced Raman spectroscopy (SM-SERS) has the potential to revolutionize quant. anal. at ultralow concns. (<1 nM). However, there are no established protocols to generalize the application of this technique in anal. chem. Here, a protocol for quantification at ultralow concns. using SM-SERS is proposed. The approach aims to take advantage of the stochastic nature of the single-mol. regime to achieved lower limits of quantification (LOQ). Two emerging contaminants commonly found in aquatic environments, enrofloxacin (ENRO) and ciprofloxacin (CIPRO), were chosen as nonresonant mol. probes. The methodol. involves a multivariate resoln. curve fitting known as nonneg. matrix factorization with alternating least-squares algorithm (NMF-ALS) to solve spectral overlaps. The key element of the quantification is to realize that, under SM-SERS conditions, the Raman intensity generated by a mol. adsorbed on a hotspot can be digitalized. Therefore, the no. of SERS event counts (rather than SERS intensities) is proportional to the soln. concn. This allowed the detn. of both ENRO and CIPRO with high accuracy and precision even at ultralow concns. regime. The LOQ for both ENRO and CIPRO were achieved at 2.8 pM. The digital SERS protocol, suggested here, is a roadmap for the implementation of SM-SERS as a routine tool for quantification at ultralow concns.
- 549Wang, W.; Srivastava, S.; Garg, A.; Xiao, C.; Hawks, S.; Pan, J.; Duggal, N.; Isaacman-VanWertz, G.; Zhou, W.; Marr, L. C.; Vikesland, P. J. Digital Surface-Enhanced Raman Spectroscopy–Lateral Flow Test Dipstick: Ultrasensitive, Rapid Virus Quantification in Environmental Dust. Environ. Sci. Technol. 2024, 58, 4926– 4936, DOI: 10.1021/acs.est.3c10311Google ScholarThere is no corresponding record for this reference.
- 550Shim, J.-E.; Kim, Y. J.; Choe, J.-H.; Lee, T. G.; You, E.-A. Single-Nanoparticle-Based Digital SERS Sensing Platform for the Accurate Quantitative Detection of SARS-CoV-2. ACS Appl. Mater. Interfaces 2022, 14, 38459– 38470, DOI: 10.1021/acsami.2c07497Google Scholar550Single-Nanoparticle-Based Digital SERS Sensing Platform for the Accurate Quantitative Detection of SARS-CoV-2Shim, Jae-Eul; Kim, Young Jun; Choe, Jong-Ho; Lee, Tae Geol; You, Eun-AhACS Applied Materials & Interfaces (2022), 14 (34), 38459-38470CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)To prevent the ongoing spread of the highly infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), accurate and early detection based on a rapid, ultrasensitive, and highly reliable sensing method is crucially important. Here, we present a bumpy core-shell surface-enhanced Raman spectroscopy (SERS) nanoprobe-based sensing platform with single-nanoparticle (SNP)-based digital SERS anal. The tailorable bumpy core-shell SERS nanoprobe with an internal self-assembled monolayer of 4-nitrobenzenethiol Raman reporters, synthesized using HEPES biol. buffer, generates a strong, uniform, and reproducible SERS signal with an SNP-level sensitive and narrowly distributed enhancement factor (2.1 x 108 to 2.2 x 109). We also propose an SNP-based digital SERS anal. method that provides direct visualization of SNP detection at ultralow concns. and reliable quantification over a wide range of concns. The bumpy core-shell SERS nanoprobe-based sensing platform with SNP-based digital SERS anal. achieves the ultrasensitive and quant. detection of the SARS-CoV-2 spike protein with a limit of detection of 7.1 x 10-16 M over a wide dynamic range from 3.7 x 10-15 to 3.7 x 10-8 M, far outperforming the conventional ELISA method for the target protein. Furthermore, it can detect mutated spike proteins from the SARS-CoV-2 variants, representing the key mutations of Alpha, Beta, Gamma, Delta, and Omicron variants. Therefore, this sensing platform can be effectively and efficiently used for the accurate and early detection of SARS-CoV-2 and be adapted for the ultrasensitive and reliable detection of other highly infectious diseases.
- 551Nam, W.; Kim, W.; Zhou, W.; You, E.-A. A digital SERS sensing platform using 3D nanolaminate plasmonic crystals coupled with Au nanoparticles for accurate quantitative detection of dopamine. Nanoscale 2021, 13, 17340– 17349, DOI: 10.1039/D1NR03691BGoogle Scholar551A digital SERS sensing platform using 3D nanolaminate plasmonic crystals coupled with Au nanoparticles for accurate quantitative detection of dopamineNam, Wonil; Kim, Wansun; Zhou, Wei; You, Eun-AhNanoscale (2021), 13 (41), 17340-17349CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)We report a digital surface-enhanced Raman spectroscopy (SERS) sensing platform using the arrays of 3D nanolaminate plasmonic crystals (NLPC) coupled with Au nanoparticles and digital (on/off) SERS signal anal. for the accurate quant. detection of dopamine (DA) at ultralow concns. 3D NLPC SERS substrates were fabricated to support the optically dense arrays of vertically-stacked multi-nanogap hotspots and combined with Raman tag-conjugated Au nanoparticles for NLPC-based dual-recognition structures. We demonstrate that the 3D NLPC-based dual-recognition structures including Au nanoparticle-induced addnl. hotspots can enable more effective SERS enhancement through the mol. recognition of DA. For the accurate quantification of DA at ultralow concns., we conducted digital SERS anal. to reduce stochastic signal variation due to various microscopic effects, including mol. orientation/position variation and the spatial distribution of nanoparticle-coupled hotspots. The digital SERS anal. allowed the SERS mapping results from the DA-specific dual-recognition structures to be converted into binary "On/Off" states; the no. of "On" events was directly correlated with low-abundance DA mols. down to 1 pM. Therefore, the digital SERS platform using the 3D NLPC-based dual-recognition structures coupled with Au nanoparticles and digital SERS signal anal. can be used not only for the ultrasensitive, accurate, and quant. detn. of DA, but also for the practical and rapid anal. of various mols. on nanostructured surfaces.
- 552Tuckmantel Bido, A.; Brolo, A. G. Digital SERS Protocol Using Au Nanoparticle-Based Extrinsic Raman Labels for the Determination of SARS-CoV-2 Spike Protein in Saliva Samples. ACS Applied Nano Materials 2023, 6, 15426– 15436, DOI: 10.1021/acsanm.3c01979Google ScholarThere is no corresponding record for this reference.
- 553Xu, J.; Xie, L.; Zhu, M.; Xiong, C.; Huang, Q.; Zhang, M.; Ren, B.; Tian, Z.; Liu, G. Rapid Sample Pretreatment Facilitating SERS Detection of Trace Weak Organic Acids/Bases in Simple Matrices. Anal. Chem. 2024, 96, 5968– 5975, DOI: 10.1021/acs.analchem.4c00229Google ScholarThere is no corresponding record for this reference.
- 554Liu, C.; Weber, S.; Peng, R.; Wu, L.; Zhang, W.-s.; Luppa, P. B.; Popp, J.; Cialla-May, D. Toward SERS-based therapeutic drug monitoring in clinical settings: Recent developments and trends. TrAC Trends in Analytical Chemistry 2023, 164, 117094, DOI: 10.1016/j.trac.2023.117094Google ScholarThere is no corresponding record for this reference.
- 555Markina, N. E.; Goryacheva, I. Y.; Markin, A. V. Sample pretreatment and SERS-based detection of ceftriaxone in urine. Anal. Bioanal. Chem. 2018, 410, 2221– 2227, DOI: 10.1007/s00216-018-0888-yGoogle Scholar555Sample pretreatment and SERS-based detection of ceftriaxone in urineMarkina, Natalia E.; Goryacheva, Irina Yu.; Markin, Alexey V.Analytical and Bioanalytical Chemistry (2018), 410 (8), 2221-2227CODEN: ABCNBP; ISSN:1618-2642. (Springer)The aim of the work is the development of the procedure for ceftriaxone (antibiotic drug of cephalosporin class) detection in urine using surface-enhanced Raman spectroscopy (SERS). Hydroxylamine stabilized silver nanoparticles were used as SERS-active material. Addnl. urine pretreatment steps were developed to eliminate the influence of creatinine on the ceftriaxone SERS signal. These steps include adjusting of the sample pH to alk. value (pH 13) and purifn. of the sample using silica gel column chromatog. Alkali pH increases SERS signal of ceftriaxone, while silica gel separates the analyte from creatinine-the main admixt. in urine which provides inappropriate SERS signal background. Addnl., total protein content up to 0.2 mg/mL (upper level for urine of healthy person) and pH deviation of initial urine do not influence on SERS signal of ceftriaxone. The proposed detection procedure enables fast (∼ 10 min) detn. of ceftriaxone in artificially spiked urine samples within 5 to 500 μg/mL range of concns. which matches the range of the drug concns. in urine after injection of therapeutically required dosages. Limits of detection (3σ) and quantification (10σ) are 0.4 and 2.0 μg/mL, correspondingly.
- 556Oakley, L. H.; Fabian, D. M.; Mayhew, H. E.; Svoboda, S. A.; Wustholz, K. L. Pretreatment Strategies for SERS Analysis of Indigo and Prussian Blue in Aged Painted Surfaces. Anal. Chem. 2012, 84, 8006– 8012, DOI: 10.1021/ac301814eGoogle Scholar556Pretreatment Strategies for SERS Analysis of Indigo and Prussian Blue in Aged Painted SurfacesOakley, Lindsay H.; Fabian, David M.; Mayhew, Hannah E.; Svoboda, Shelley A.; Wustholz, Kristin L.Analytical Chemistry (Washington, DC, United States) (2012), 84 (18), 8006-8012CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Surface-enhanced Raman scattering (SERS) spectroscopy is increasingly applied to the identification of org. colorants in cultural heritage objects because vibrational fingerprints can be measured from microscopic samples. However, the development of SERS into a reliable, broad-spectrum method for art anal. requires the study of a wide variety of org. and inorg. colorants as well as colorant mixts. in paint. Here, we demonstrate reliable protocols for SERS-based identification of insol. indigo, Prussian blue (PB), and mixts. thereof in aged painted surfaces. The use of simple salts and acids for sample pretreatment is evaluated. High-quality SERS spectra of PB and indigo are elucidated upon sample pretreatment with H2SO4. In several cases, SERS spectra of the colorants could not be obtained without sample pretreatment. We demonstrate the use of H2SO4 to solubilize PB as well as perform an in situ conversion of insol. indigo to sol. indigo carmine (IC) on indigo, indigo oil paint, and actual samples from historic painted surfaces. A microscopic H2SO4-treated sample from the Portrait of Evelyn Byrd produced a SERS spectrum that is consistent with a mixt. of PB and IC. To our knowledge, this work represents the first SERS spectrum of indigo in oil paint and the first simultaneous detection of a mixt. of blue org. and inorg. colorants in a single art sample using SERS.
- 557Song, C.; Li, J.; Sun, Y.; Jiang, X.; Zhang, J.; Dong, C.; Wang, L. Colorimetric/SERS dual-mode detection of mercury ion via SERS-Active peroxidase-like Au@AgPt NPs. Sens. Actuators, B 2020, 310, 127849, DOI: 10.1016/j.snb.2020.127849Google Scholar557Colorimetric/SERS dual-mode detection of mercury ion via SERS-Active peroxidase-like Au@AgPt NPsSong, Chunyuan; Li, Jinxiang; Sun, Youzhi; Jiang, Xinyu; Zhang, Jingjing; Dong, Chen; Wang, LianhuiSensors and Actuators, B: Chemical (2020), 310 (), 127849CODEN: SABCEB; ISSN:0925-4005. (Elsevier B.V.)The development of mercury ion (Hg2+) probes integrating the ability of facile preliminary evaluation and high-sensitive accurate assay with wide detection range is very important for water pollution prevention and human health. Herein, a novel colorimetric/SERS dual-mode detection of Hg2+ was proposed by using the SERS-active peroxidase-like Au@AgPt NPs. The Au@AgPt NP has hexoctahedral Au nanoparticle core with edges coating by Pt, which shows good SERS activity of Au and enhanced catalyst activity of Pt for designing colorimetric/SERS dual-mode probes. Basing on the colorimetric assay, 5μM-1 mM Hg2+ can be facile obsd. by naked eye and a linear sensing (1μM-100 M μ) with limit of detection (LOD) of 0.52μM was obtained by absorption anal. Besides, a linear calibration curve from 1 nM to 10μM was achieved by SERS with LOD of 0.28 nM. The proposed dual-mode probes with good selectivity and reliability integrate the advantages of facile detection by colorimetric anal. and high-sensitive trace assay by SERS, and possess relatively better performance on sensitivity and detection range in comparison to the previous probes/methods, which can be served as efficient probes for monitoring water quality.
- 558Dinish, U. S.; Song, Z.; Ho, C. J. H.; Balasundaram, G.; Attia, A. B. E.; Lu, X.; Tang, B. Z.; Liu, B.; Olivo, M. Single Molecule with Dual Function on Nanogold: Biofunctionalized Construct for In Vivo Photoacoustic Imaging and SERS Biosensing. Adv. Funct. Mater. 2015, 25, 2316– 2325, DOI: 10.1002/adfm.201404341Google Scholar558Single Molecule with Dual Function on Nanogold: Biofunctionalized Construct for In Vivo Photoacoustic Imaging and SERS BiosensingDinish, U. S.; Song, Zhegang; Ho, Chris Jun Hui; Balasundaram, Ghayathri; Attia, Amalina Binte Ebrahim; Lu, Xianmao; Tang, Ben Zhong; Liu, Bin; Olivo, MaliniAdvanced Functional Materials (2015), 25 (15), 2316-2325CODEN: AFMDC6; ISSN:1616-301X. (Wiley-VCH Verlag GmbH & Co. KGaA)Multimodal imaging provides complimentary information that is advantageous in studying both cellular and mol. mechanisms in vivo, which has tremendous potential in pre-clin. research and clin. translational imaging. It is desirable to design probes for multimodal imaging that can be administered minimally but provides multifaceted information. Herein, the authors demonstrate the complimentary dual functional ability of a nanoconstruct for mol. imaging in both photoacoustic (PA) and surface-enhanced Raman scattering (SERS) biosensing simultaneously in tandem. To realize this, a group of NIR active org. mols. are designed and synthesized that possess both SERS and PA activity. Nanoconstructs realized by anchoring such mols. onto gold nanoparticles are demonstrated for targeting cancer biomarkers in vivo while providing complimentary information about biodistribution and targeting efficiency. In future, such nanoconstructs could play a major role in identifying surgical margins and also for disease monitoring in translational medicine.
- 559Kenry; Nicolson, F.; Clark, L.; Panikkanvalappil, S. R.; Andreiuk, B.; Andreou, C. Advances in Surface Enhanced Raman Spectroscopy for in Vivo Imaging in Oncology. Nanotheranostics 2022, 6, 31– 49, DOI: 10.7150/ntno.62970Google ScholarThere is no corresponding record for this reference.
- 560Xu, J.; Zhang, B.; Zhang, Y.; Mai, L.; Hu, W.; Chen, C.-J.; Liu, J.-T.; Zhu, G. Recent advances in disease diagnosis based on electrochemical-optical dual-mode detection method. Talanta 2023, 253, 124037, DOI: 10.1016/j.talanta.2022.124037Google Scholar560Recent advances in disease diagnosis based on electrochemical-optical dual-mode detection methodXu, Jiaqi; Zhang, Bo; Zhang, Yao; Mai, Luyu; Hu, Wenhao; Chen, Ching-Jung; Liu, Jen-Tsai; Zhu, GuixianTalanta (2023), 253 (), 124037CODEN: TLNTA2; ISSN:0039-9140. (Elsevier B.V.)A review. The electrochem. method is commonly applied in diagnosing and monitoring diseases. When used in conjunction with optical disease detection systems, it can broaden the detection range, lower the limit of detection and create mutual confirmation. Utilizing the electrochem.-optical dual-mode detection method for disease diagnosis is non-invasive, low-cost, easy-to-use, efficient and accurate compared with the traditional single-mode method. This paper reviews the reports of electrochem. and optical methods combined in recent years, such as colorimetry, fluorescence, Surface Enhanced Raman Spectroscopy (SERS), surface plasmon resonance (SPR) and spectroelectrochem. We cover researches on several electrochem.-optical dual-mode detection methods for identifying disease markers, including biochem., cancer, infection, cardiovascular and cerebrovascular disease, and neurol. diseases as well. These studies demonstrate the feasibility of electrochem.-optical dual-mode detection and its broad application prospects in the field of disease detection.
- 561Li, M.; Lin, H.; Paidi, S. K.; Mesyngier, N.; Preheim, S.; Barman, I. A Fluorescence and Surface-Enhanced Raman Spectroscopic Dual-Modal Aptasensor for Sensitive Detection of Cyanotoxins. ACS Sens. 2020, 5, 1419– 1426, DOI: 10.1021/acssensors.0c00307Google Scholar561A Fluorescence and Surface-Enhanced Raman Spectroscopic Dual-Modal Aptasensor for Sensitive Detection of CyanotoxinsLi, Ming; Lin, Hangduo; Paidi, Santosh Kumar; Mesyngier, Nicolas; Preheim, Sarah; Barman, IshanACS Sensors (2020), 5 (5), 1419-1426CODEN: ASCEFJ; ISSN:2379-3694. (American Chemical Society)The ability to detect trace analytes without necessitating solid surface attachment or complicated processing steps would facilitate the translation of sensors for monitoring environmental toxins in the field. To address a crit. unmet need in fresh water ecol., we have developed a dual-modal aptamer-based biosensor (aptasensor), featuring fluorescence and surface-enhanced Raman spectroscopy (SERS), for sensitive and selective detection of hepatotoxin microcystin-LR (MC-LR). The rational sensor design is based on the high affinity of the cyanine (Cy3) dye-modified complementary DNA (Cy3-cDNA) strand toward the plasmonic gold nanostars (GNSs) in comparison to the Cy3-cDNA/aptamer duplex. The preferential binding of MC-LR toward the MC-LR-specific aptamer triggers the dissocn. of Cy3-cDNA/aptamer duplexes, which switches the Cy3's fluorescence "off" and SERS "on" due to the proximity of Cy3 dye to the GNS surface. Both fluorescence and SERS intensities are obsd. to vary linearly with the MC-LR concn. over the range of investigation. We have achieved high sensitivity and excellent specificity with the aptasensor toward MC-LR, which can be attributed to the fluorescence quenching effect, significant SERS enhancement by the GNSs, and the high affinity of the aptamer toward the MC-LR analytes. We further demonstrate the applicability of the present aptasensor for detection of MC-LR in a diverse set of real water samples with high accuracy and excellent reproducibility. With further refinement, we believe that the aptamer-driven complementary assembly of the SERS and fluorescence sensing constructs can be applied for rapid, multiplexed, and robust measurements of environmental toxins in the field.
- 562Jeanmaire, D. L.; Van Duyne, R. P. Surface raman spectroelectrochemistry: Part I. Heterocyclic, aromatic, and aliphatic amines adsorbed on the anodized silver electrode. Journal of Electroanalytical Chemistry and Interfacial Electrochemistry 1977, 84, 1– 20, DOI: 10.1016/S0022-0728(77)80224-6Google Scholar562Surface Raman spectroelectrochemistry. Part I. Heterocyclic, aromatic, and aliphatic amines adsorbed on the anodized silver electrodeJeanmaire, David L.; Van Duyne, Richard P.Journal of Electroanalytical Chemistry and Interfacial Electrochemistry (1977), 84 (1), 1-20CODEN: JEIEBC; ISSN:0022-0728.The remarkable sensitivity of Raman spectroscopy was verified for the study of adsorbed pyridine on a Ag surface, and its applicability extended to other N heterocycles and amines. New bands in the scattering spectrum of adsorbed pyridine were characterized, which were not previously reported, as well as the Raman intensity response of all the surface pyridine bands as a function of electrode potential. As a result of these expts., a model is proposed of the adsorbed species for pyridine in which the adsorption is anion induced, leading to an axial end-on attachment to the electrode surface. The ability to obtain resonance Raman spectra with good signal-to-noise ratios with laser powers < 1.0 mW, opens up possibilities of surface Raman studies with relatively inexpensive laser systems. As laser power requirements are relaxed, reliability is improved, and greater tuning ranges can be achieved for wavelength dependent studies. The potential of resonance Raman spectroscopy was previously demonstrated for monitoring soln. kinetic behavior; now it is shown that normal Raman as well as resonance Raman spectroscopy have sufficient sensitivity to extend the studies of kinetic processes to include those occurring at electrode surfaces.
- 563Brosseau, C. L.; Colina, A.; Perales-Rondon, J. V.; Wilson, A. J.; Joshi, P. B.; Ren, B.; Wang, X. Electrochemical surface-enhanced Raman spectroscopy. Nat. Rev. Methods Prim. 2023, 3, 79, DOI: 10.1038/s43586-023-00263-6Google ScholarThere is no corresponding record for this reference.
- 564Markin, A. V.; Arzhanukhina, A. I.; Markina, N. E.; Goryacheva, I. Y. Analytical performance of electrochemical surface-enhanced Raman spectroscopy: A critical review. TrAC Trends in Analytical Chemistry 2022, 157, 116776, DOI: 10.1016/j.trac.2022.116776Google ScholarThere is no corresponding record for this reference.
- 565Gu, X.; Wang, K.; Qiu, J.; Wang, Y.; Tian, S.; He, Z.; Zong, R.; Kraatz, H.-B. Enhanced electrochemical and SERS signals by self-assembled gold microelectrode arrays: A dual readout platform for multiplex immumoassay of tumor biomarkers. Sens. Actuators, B 2021, 334, 129674, DOI: 10.1016/j.snb.2021.129674Google Scholar565Enhanced electrochemical and SERS signals by self-assembled gold microelectrode arrays: A dual readout platform for multiplex immumoassay of tumor biomarkersGu, Xuefang; Wang, Kaiyue; Qiu, Jiawei; Wang, Yajie; Tian, Shu; He, Zhenkuan; Zong, Ran; Kraatz, Heinz-BernhardSensors and Actuators, B: Chemical (2021), 334 (), 129674CODEN: SABCEB; ISSN:0925-4005. (Elsevier B.V.)In this study, a dual readout biosensor is reported that combines electrochem. and surface-enhanced Raman scattering (SERS) for a multiplexed immunoassay of tumor biomarkers. A gold microelectrode array (GMA) was fabricated by electrodeposition of Au to the bottom of numerous individual silica cavities. Electrochem. studies demonstrate that the GMA possesses unique charge selectivity and an inherently high S/N ratio, which make the GMA esp. suitable for differential pulse voltammetry (DPV) and square wave voltammetry (SWV) detection. Hybridization chain reaction (HCR) was designed to increase the load of labeled mols. in this super-sandwich structured biosensor. Meanwhile, the strong plasmon coupling between silver nanoparticles and the underlying gold particles enabled ultrahigh sensitivity of the GMA when using SERS readout. By combining electrochem. and SERS methods, we achieved the high-throughput preliminary screening of alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA). Further quant. anal. showed that the two proteins could be detd. in a wide concn. range, and their min. detection limits were 0.6 and 0.3 pg·mL-1 when using SERS method, resp. The applicability of the proposed dual readout platform in clin. diagnosis was verified by the detection in human serum samples.
- 566SPELEC Raman Electrochemistry. Metrohm. https://www.metrohm.com/en/products/electrochemistry/spelec-spectroelectrochemistry/SPELECRAMAN.Google ScholarThere is no corresponding record for this reference.
- 567Sardar, S.; Fabris, L.; Javanmard, M. Improved Precision in Surface-Enhanced Raman Scattering Quantification of Analyte through Dual-Modality Multisite Sensing. Anal. Chem. 2019, 91, 4323– 4330, DOI: 10.1021/acs.analchem.8b02559Google Scholar567Improved Precision in Surface-Enhanced Raman Scattering Quantification of Analyte through Dual-Modality Multisite SensingSardar, Sakshi; Fabris, Laura; Javanmard, MehdiAnalytical Chemistry (Washington, DC, United States) (2019), 91 (7), 4323-4330CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Accurate quantification of analyte using surface-enhanced Raman spectroscopy (SERS) is a desired, yet unfulfilled, ability that could enable a plethora of diagnostic- and defense-related applications. The major hurdles to overcome to achieve this goal are expensive manufg. for highly ordered and reproducible substrates and low reproducibility of substrates produced through low cost methods. A technol. that can set industry stds. for manufg./processing of SERS substrates is still yet to be achieved. A dual-modality multisite sensing approach was developed, that overcomes the limitations experienced when fabricating bottom-up, reproducible, sensitive, and low-cost SERS substrates. Electrochem. was combined with SERS for dual-modality sensing to improve precision by adding redundancy and encoding features, thus increasing measurement robustness and predictability. This technique works by calibrating SERS response with respect to active surface area, a parameter known to be proportional to charge, which can be estd. via electrochem. measurements. The dual-modality multisite measurement demonstrates at least 2.8× improvement in assay precision compared to the traditional single-site Raman measurements. The technique yields overall improved precision of measurement and is not limited to any particular SERS substrate or geometry, and thus it can be adapted and incorporated readily in any SERS sensing assay.
- 568Fabris, L. Bottom-up optimization of SERS hot-spots. Chem. Commun. 2012, 48, 9346– 9348, DOI: 10.1039/c2cc34068bGoogle Scholar568Bottom-up optimization of SERS hot-spotsFabris, LauraChemical Communications (Cambridge, United Kingdom) (2012), 48 (75), 9346-9348CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)The bottom-up optimization of signal-to-noise ratios for SERS tags employing SAMSA fluorescein as the reporter was achieved using a bifunctional linker with low Raman cross section. By holding the nanoparticles at sub-nm sepn., the linker allowed one to optimize the hot-spot thereby significantly reducing the fluorescence background.
- 569Dardir, K.; Wang, H.; Martin, B. E.; Atzampou, M.; Brooke, C. B.; Fabris, L. SERS Nanoprobe for Intracellular Monitoring of Viral Mutations. J. Phys. Chem. C 2020, 124, 3211– 3217, DOI: 10.1021/acs.jpcc.9b09253Google Scholar569SERS Nanoprobe for Intracellular Monitoring of Viral MutationsDardir, Kholud; Wang, Hao; Martin, Brigitte E.; Atzampou, Maria; Brooke, Christopher B.; Fabris, LauraJournal of Physical Chemistry C (2020), 124 (5), 3211-3217CODEN: JPCCCK; ISSN:1932-7447. (American Chemical Society)Gold nanostars, functionalized with thiolated DNA hairpins bearing a Raman-active fluorescent dye at the 3' terminus, were engineered to identify and quantify RNA mutations in the influenza A virus (IAV) genome employing surface enhanced Raman spectroscopy (SERS). The DNA hairpin structure was designed to selectively extend/fold in the absence/presence of the viral RNA targets, resulting in the fluorophore being brought away from or close to the gold nanostar surface, leading to an "OFF-ON" switching of the SERS signal. Validation of the switchable SERS nanostar probes was first carried out in buffer, showing that the detection is sequence-specific and that the high sensitivity provided by these SERS probes allows target detection at the single particle level. We also demonstrate that the degree of signal recovery can be closely correlated with the no. of genetic mutations. Further expts. carried out with HeLa cell lysate spiked with RNA oligonucleotides demonstrate that the functionality of these nanoprobes were not detrimentally affected by the complex matrix. As a proof of concept, we also tested these nanoparticle probes in vitro by specifically targeting the hemagglutinin (HA) segment in live HeLa cells transfected with plasmids coding for either HA or two other IAV segments, PB1 and PB2, as neg. controls. The intracellular SERS response in individual transfected HeLa cells demonstrates high sequence-selectivity of the probes for the HA segment, suggesting the applicability of these probes for multiplexed detection and quantification of viral RNAs in individual cells with an approach that can account for the viral population diversity. This also represents the first time that mol. beacon-based SERS probes have been employed to detect viral RNA target in intact individual cells.
- 570Wang, H.; Dardir, K.; Lee, K. B.; Fabris, L. Impact of Protein Corona in Nanoflare-Based Biomolecular Detection and Quantification. Bioconjugate Chem. 2019, 30, 2555– 2562, DOI: 10.1021/acs.bioconjchem.9b00495Google Scholar570Impact of Protein Corona in Nanoflare-Based Biomolecular Detection and QuantificationWang, Hao; Dardir, Kholud; Lee, Ki-Bum; Fabris, LauraBioconjugate Chemistry (2019), 30 (10), 2555-2562CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)Selective detection and precise quantification of biomols. in intracellular settings play a pivotal role in the diagnostics and therapeutics of diseases, including various cancers and infectious epidemics. Because of this clin. relevance, nanoprobes with high sensitivity, wide tunability, and excellent biol. stability have become of high demand. In particular, nanoflares based on gold nanoparticles have emerged as an attractive candidate for intracellular detection due to their efficient cellular uptake, enhanced binding affinity with complementary targets, and improved biol. compatibility. However, nanoprobes, including these nanoflares, are known to be susceptible to the adsorption of proteins present in the biol. environment which leads to the formation of a so-called protein corona layer on their surface, leading to an altered targeting efficiency and cellular uptake. In this work, the authors leverage the nanoflares platform to demonstrate the effect of protein corona on biomol. detection, quantification, as well as biol. stability against enzymic degrdn. Nanoflares incubated in a biol. relevant concn. of serum albumin proteins (0.50%) were shown to result in more than 20% signal redn. in target detection, with a decrease varying proportionally with the protein concns. In addn., similar signal redn. was obsd. for different serum proteins, and PEG backfilling was found to be ineffective in mitigating the neg. impact induced by the corona formation. Furthermore, nuclease resistance in nanoflares was also severely compromised by the presence of the corona shell (∼ 2 folds increase in hydrolysis activity). This work demonstrates the consequences of an in-situ formed protein corona layer on mol. detection/quantification and biol. stability of nanoflares in the presence of nuclease enzymes, highlighting the importance of calibrating similar nanoprobes in proper biol. media to improve the accuracy of mol. detection and quantification.
- 571Bhamidipati, M.; Cho, H. Y.; Lee, K. B.; Fabris, L. SERS-Based Quantification of Biomarker Expression at the Single Cell Level Enabled by Gold Nanostars and Truncated Aptamers. Bioconjugate Chem. 2018, 29, 2970– 2981, DOI: 10.1021/acs.bioconjchem.8b00397Google Scholar571SERS-Based Quantification of Biomarker Expression at the Single Cell Level Enabled by Gold Nanostars and Truncated AptamersBhamidipati, Manjari; Cho, Hyeon-Yeol; Lee, Ki-Bum; Fabris, LauraBioconjugate Chemistry (2018), 29 (9), 2970-2981CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)Surface-enhanced Raman spectroscopy (SERS)-based biosensors have been used increasingly over the past few years for cancer detection and diagnosis. SERS-based imaging offers excellent sensitivity and has advantages over other detection techniques such as fluorescence. The authors developed a novel biosensor to detect the cancer biomarker epithelial cell adhesion mol. (EpCAM) and quantify its expression at the single cell level. EpCAM is one of the most commonly expressed markers on a variety of cancer cells; importantly it has been suggested that redn. of its expression levels could be assocd. with the epithelial to mesenchymal transition (EMT) and thus to the onset of metastasis. Therefore, monitoring variations in expression levels of this membrane biomarker would improve the authors' ability to monitor cancer progression. The described substrate-based biosensor was developed employing gold nanostars functionalized with EpCAM aptamer mols. and was able to quantify subnanomolar concns. of EpCAM protein in soln. Importantly, the authors demonstrated its use to quantify EpCAM expression on the surface of two cancer cells, MCF-7 and PC-3. The authors also compared the binding efficiency of two EpCAM DNA aptamers of different lengths and obsd. a substantial improvement in the sensitivity of detection by employing the shorter aptamer sequence, probably due to the reduced no. of conformations possible at room temp. with the truncated oligonucleotide. Detailed characterization of the substrates was carried out using both SERS maps and at. force microscopy. These substrate-based diagnostic devices promise to be relevant for monitoring phenotype evolutions in cancer cells, blood, and other bodily fluids, thus improving the authors' ability to follow in real time disease onset and progression.
- 572Bhamidipati, M.; Lee, G.; Kim, I.; Fabris, L. SERS-Based Quantification of PSMA in Tissue Microarrays Allows Effective Stratification of Patients with Prostate Cancer. ACS Omega 2018, 3, 16784– 16794, DOI: 10.1021/acsomega.8b01839Google Scholar572SERS-Based Quantification of PSMA in Tissue Microarrays Allows Effective Stratification of Patients with Prostate CancerBhamidipati, Manjari; Lee, Geuntaek; Kim, Isaac; Fabris, LauraACS Omega (2018), 3 (12), 16784-16794CODEN: ACSODF; ISSN:2470-1343. (American Chemical Society)Prostate specific membrane antigen (PSMA), a type II membrane protein, is an attractive biomarker that has been validated clin. for the diagnosis of prostate cancer. The authors developed SERS nanoprobes for PSMA detection and quantification at the single cell level on prostate cancer cells. The cells were targeted employing SERS nanoprobes that consisted of gold nanostars functionalized with PSMA aptamer mols. The authors were able to quantify picomolar concns. of sol. PSMA protein and used the resulting calibration curve to est. the expression of PSMA on the surface of the prostate cancer cell, LNCaP, at the single cell level. Importantly, the authors employed these SERS tags to stratify prostate cancer patients by assessing PSMA expression in tissues contained in a prostate tissue microarray. The stratification results clearly correlated PSMA expression to recommended therapy groups, rendering the described method an effective tool to aid in designing personalized therapeutic protocols. Benchmarking detection sensitivity against immunofluorescence staining and comparing stratification results obtained with the two methods allowed the authors to validate the authors' novel approach against std. practices. Based on these results, the authors confirm the validity of PSMA as an effective biomarker for prostate cancer patient evaluation and propose SERS-based diagnostic techniques as integrative methods for the assessment of disease stage and the identification of effective therapeutic protocols.
- 573Si, Y.; Xu, L.; Deng, T.; Zheng, J.; Li, J. Catalytic Hairpin Self-Assembly-Based SERS Sensor Array for the Simultaneous Measurement of Multiple Cancer-Associated miRNAs. ACS Sens. 2020, 5, 4009– 4016, DOI: 10.1021/acssensors.0c01876Google Scholar573Catalytic Hairpin Self-Assembly-Based SERS Sensor Array for the Simultaneous Measurement of Multiple Cancer-Associated miRNAsSi, Yanmei; Xu, Lan; Deng, Ting; Zheng, Jing; Li, JishanACS Sensors (2020), 5 (12), 4009-4016CODEN: ASCEFJ; ISSN:2379-3694. (American Chemical Society)The abnormal expression of some miRNAs is often closely related to the development of tumors. Available detection methods or biosensors that can simultaneously quantify multiple miRNAs in a single sample have rarely been reported. Herein, a novel catalytic hairpin self-assembly (CHA)-based surface-enhanced Raman scattering (SERS) sensor array was developed to simultaneously measure multiple miRNAs assocd. with cancer in one sample. The sensor array with four different sensing units was constructed by immobilizing one of four different hairpin-structured DNA sequence 1 (hp1) onto one of four Au/Ag alloy nanoparticle (AuAgNP)-coated detection wells. When target miRNA is present, the SERS tags, which were prepd. by modifying AuAgNPs with a Raman reporter mol. of 4-mercaptobenzonitrile (MPBN) and the related hairpin-structured DNA sequence 2 (hp2), were captured onto the corresponding sensor unit through a repeated specific CHA reaction. This generated many "hot spots" because of interactions between the SERS tags and the AuAgNP layer-coated surface of the sensor, which ultimately produced a strong SERS signal that allowed the detection of target miRNAs with the detection limit of 0.15 pM. Using this SERS sensor array, multiple cancer-assocd. miRNAs (miR-1246, miR-221, miR-133a, and miR-21) were successfully detd. in buffer, serum, and cellular RNA exts.
- 574Cao, X.; Sun, Y.; Mao, Y.; Ran, M.; Liu, Y.; Lu, D.; Bi, C. Rapid and sensitive detection of dual lung cancer-associated miRNA biomarkers by a novel SERS-LFA strip coupling with catalytic hairpin assembly signal amplification. Journal of Materials Chemistry C 2021, 9, 3661– 3671, DOI: 10.1039/D0TC05737AGoogle ScholarThere is no corresponding record for this reference.
- 575Mao, Y.; Sun, Y.; Xue, J.; Lu, W.; Cao, X. Ultra-sensitive and high efficiency detection of multiple non-small cell lung cancer-related miRNAs on a single test line in catalytic hairpin assembly-based SERS-LFA strip. Anal. Chim. Acta 2021, 1178, 338800, DOI: 10.1016/j.aca.2021.338800Google ScholarThere is no corresponding record for this reference.
- 576Wu, J.; Zhou, X.; Li, P.; Lin, X.; Wang, J.; Hu, Z.; Zhang, P.; Chen, D.; Cai, H.; Niessner, R.; Haisch, C.; Sun, P.; Zheng, Y.; Jiang, Z.; Zhou, H. Ultrasensitive and Simultaneous SERS Detection of Multiplex MicroRNA Using Fractal Gold Nanotags for Early Diagnosis and Prognosis of Hepatocellular Carcinoma. Anal. Chem. 2021, 93, 8799– 8809, DOI: 10.1021/acs.analchem.1c00478Google Scholar576Ultrasensitive and Simultaneous SERS Detection of Multiplex MicroRNA Using Fractal Gold Nanotags for Early Diagnosis and Prognosis of Hepatocellular CarcinomaWu, Jiamin; Zhou, Xia; Li, Ping; Lin, Xiaoling; Wang, Jinhua; Hu, Ziwei; Zhang, Pengcheng; Chen, Dong; Cai, Huaihong; Niessner, Reinhard; Haisch, Christoph; Sun, Pinghua; Zheng, Yun; Jiang, Zhengjin; Zhou, HaiboAnalytical Chemistry (Washington, DC, United States) (2021), 93 (25), 8799-8809CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Sensitive and simultaneous detection of multiple cancer-related biomarkers in serum is essential for diagnosis, therapy, prognosis, and staging of cancer. Herein, we proposed a magnetically assisted sandwich-type surface-enhanced Raman scattering (SERS)-based biosensor for ultrasensitive and multiplex detection of three hepatocellular carcinoma-related microRNA (miRNA) biomarkers. The biosensor consists of an SERS tag (probe DNA-conjugated DNA-engineered fractal gold nanoparticles, F-AuNPs) and a magnetic capture substrate (capture DNA-conjugated Ag-coated magnetic nanoparticles, AgMNPs). The proposed strategy achieved simultaneous and sensitive detection of three miRNAs (miRNA-122, miRNA-223, and miRNA-21), and the limits of detection of the three miRNAs in human serum are 349 aM for miRNA-122, 374 aM for miRNA-223, and 311 aM for miRNA-21. High selectivity and accuracy of the SERS biosensor were proved by practical anal. in human serum. Moreover, the biosensor exhibited good practicability in multiplex detection of three miRNAs in 92 clin. sera from AFP-neg. patients, patients before and after hepatectomy, recurred and relapse-free patients after hepatectomy, and hepatocellular carcinoma patients at distinct Barcelona clinic liver cancer stages. The expt. results demonstrate that our SERS-based assay is a promising candidate in clin. application and exhibited potential for the prediction, diagnosis, monitoring, and staging of cancers.
- 577Lyu, N.; Rajendran, V. K.; Diefenbach, R. J.; Charles, K.; Clarke, S. J.; Engel, A.; Rizos, H.; Molloy, M. P.; Wang, Y. Multiplex detection of ctDNA mutations in plasma of colorectal cancer patients by PCR/SERS assay. Nanotheranostics 2020, 4, 224– 232, DOI: 10.7150/ntno.48905Google Scholar577Multiplex detection of ctDNA mutations in plasma of colorectal cancer patients by PCR/SERS assayLyu Nana; Rajendran Vinoth Kumar; Wang Yuling; Diefenbach Russell J; Rizos Helen; Diefenbach Russell J; Charles Kellie; Clarke Stephen J; Engel Alexander; Molloy Mark PNanotheranostics (2020), 4 (4), 224-232 ISSN:.Molecular diagnostic testing of KRAS and BRAF mutations has become critical in the management of colorectal cancer (CRC) patients. Some progress has been made in liquid biopsy detection of mutations in circulating tumor DNA (ctDNA), which is a fraction of circulating cell-free DNA (cfDNA), but slow analysis for DNA sequencing methods has limited rapid diagnostics. Other methods such as quantitative PCR and more recently, droplet digital PCR (ddPCR), have limitations in multiplexed capacity and the need for expensive specialized equipment. Hence, a robust, rapid and facile strategy is needed for detecting multiple ctDNA mutations to improve the management of CRC patients. To address this significant problem, herein, we propose a new application of multiplex PCR/SERS (surface-enhanced Raman scattering) assay for the detection of ctDNA in CRC, in a fast and non-invasive manner to diagnose and stratify patients for effective treatment. Methods: To discriminate ctDNA mutations from wild-type cfDNA, allele-specific primers were designed for the amplification of three clinically important DNA point mutations in CRC including KRAS G12V, KRAS G13D and BRAF V600E. Surface-enhanced Raman scattering (SERS) nanotags were labelled with a short and specific sequence of oligonucleotide, which can hybridize with the corresponding PCR amplicons. The PCR/SERS assay was implemented by firstly amplifying the multiple mutations, followed by binding with multicolor SERS nanotags specific to each mutation, and subsequent enrichment with magnetic beads. The mutation status was evaluated using a portable Raman spectrometer where the fingerprint spectral peaks of the corresponding SERS nanotags indicate the presence of the mutant targets. The method was then applied to detect ctDNA from CRC patients under a blinded test, the results were further validated by ddPCR. Results: The PCR/SERS strategy showed high specificity and sensitivity for genotyping CRC cell lines and plasma ctDNA, where as few as 0.1% mutant alleles could be detected from a background of abundant wild-type cfDNA. The blinded test using 9 samples from advanced CRC patients by PCR/SERS assay was validated with ddPCR and showed good consistency with pathology testing results. Conclusions: With ddPCR-like sensitivity yet at the convenience of standard PCR, the proposed assay shows great potential in sensitive detection of multiple ctDNA mutations for clinical decision-making.
- 578Makanai, H.; Nishihara, T.; Tanabe, K. Surface-Enhanced Raman Scattering Identification of Nucleic Acid Targets by Acetylene-Tagged Hoechst Molecule Binding with DNA-Tethered Gold Nanoparticles. ACS Applied Nano Materials 2022, 5, 2935– 2942, DOI: 10.1021/acsanm.2c00213Google ScholarThere is no corresponding record for this reference.
- 579Jang, A. S.; Praveen Kumar, P. P.; Lim, D.-K. Attomolar Sensitive Magnetic Microparticles and a Surface-Enhanced Raman Scattering-Based Assay for Detecting SARS-CoV-2 Nucleic Acid Targets. ACS Appl. Mater. Interfaces 2022, 14, 138– 149, DOI: 10.1021/acsami.1c17028Google Scholar579Attomolar Sensitive Magnetic Microparticles and a Surface-Enhanced Raman Scattering-Based Assay for Detecting SARS-CoV-2 Nucleic Acid TargetsJang, Ah Seong; Praveen Kumar, Panangattukara Prabhakaran; Lim, Dong-KwonACS Applied Materials & Interfaces (2022), 14 (1), 138-149CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Highly sensitive, reliable assays with strong multiplexing capability for detecting nucleic acid targets are significantly important for diagnosing various diseases, particularly severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The nanomaterial-based assay platforms suffer from several crit. issues such as non-specific binding and highly false-pos. results. In this paper, to overcome such limitations, we reported sensitive and remarkably reproducible magnetic microparticles (MMPs) and a surface-enhanced Raman scattering (SERS)-based assay using stable silver nanoparticle clusters for detecting viral nucleic acids. The MMP-SERS-based assay exhibited a sensitivity of 1.0 fM, which is superior to the MMP-fluorescence-based assay. In addn., in the presence of anisotropic Ag nanostructures (nanostars and triangular nanoplates), the assay exhibited greatly enhanced sensitivity (10 aM) and excellent signal reproducibility. This assay platform intrinsically eliminated the non-specific binding that occurs in the target detection step, and the controlled formation of stable silver nanoparticle clusters in soln. enabled the remarkable reproducibility of the results. These findings indicate that this assay can be employed for future practical bioanal. applications.
- 580Hou, M.; He, D.; Wang, H.; Huang, J.; Cheng, H.; Wan, K.; Li, H.-W.; Tang, Z.; He, X.; Wang, K. Simultaneous and multiplex detection of exosomal microRNAs based on the asymmetric Au@Au@Ag probes with enhanced Raman signal. Chin. Chem. Lett. 2022, 33, 3183– 3187, DOI: 10.1016/j.cclet.2021.11.092Google Scholar580Simultaneous and multiplex detection of exosomal microRNAs based on the asymmetric Au@Au@Ag probes with enhanced Raman signalHou, Min; He, Dinggeng; Wang, Huizhen; Huang, Jin; Cheng, Hong; Wan, Kejin; Li, Hung-Wing; Tang, Zifeng; He, Xiaoxiao; Wang, KeminChinese Chemical Letters (2022), 33 (6), 3183-3187CODEN: CCLEE7; ISSN:1001-8417. (Elsevier B.V.)Simultaneous and quant. detection of multiple exosomal microRNAs (miRNAs) was successfully performed by a surface-enhanced Raman scattering (SERS) assay consisting of Raman probes and capture probes. In this design, the asym. core-shell structured Au@Au@Ag nanoparticles were first synthesized by layer-by-layer self-assembly method and modified with different Raman mols. and recognition sequences (polyA-DNA) to prep. the surface-enhanced Raman probes. Then, the streptavidin-modified magnetic beads were used to immobilize the biotinylated DNA capture sequences (biotin-DNA) to obtain capture probes. In the presence of target exosomal miRNAs, the Raman probes and capture probes could bind to the target exosomal miRNAs in the partial hybridization manner. Thus, the developed SERS sensor could indicate the target miRNAs levels in the buffer soln. Using breast cancer-related miRNAs as model targets, the limits of detection of this sensor were detd. to be 1.076 fmol/L for synthetic miR-21, 0.068 fmol/L for synthetic miR-126, and 4.57 fmol/L for synthetic miR-1246, resp. Such SERS sensors were further employed to detect the miR-21 in 20% human serum and the extn. soln. of exosomes, resp. Therefore, simultaneous and multiplex detection of cancer-related exosomal miRNAs by this assay could provide new opportunities for further biomedical applications.
- 581Xu, W.; Zhang, Y.; Hou, D.; Shen, J.; Dong, J.; Gao, Z.; Liu, H. Quantitative SERS detection of multiple breast cancer miRNAs based on duplex specific nuclease-mediated signal amplification. Anal. Methods 2023, 15, 2915– 2924, DOI: 10.1039/D3AY00583FGoogle ScholarThere is no corresponding record for this reference.
- 582Zeng, Y.; Koo, K. M.; Shen, A. G.; Hu, J. M.; Trau, M. Nucleic Acid Hybridization-Based Noise Suppression for Ultraselective Multiplexed Amplification of Mutant Variants. Small 2021, 17, e2006370, DOI: 10.1002/smll.202006370Google Scholar582Nucleic Acid Hybridization-Based Noise Suppression for Ultraselective Multiplexed Amplification of Mutant VariantsZeng, Yi; Koo, Kevin M.; Shen, Ai-Guo; Hu, Ji-Ming; Trau, MattSmall (2021), 17 (2), 2006370CODEN: SMALBC; ISSN:1613-6810. (Wiley-VCH Verlag GmbH & Co. KGaA)The anal. of mutant nucleic acid (NA) variants can provide crucial clin. and biol. insights for many diseases. Yet, existing anal. techniques are generally constrained by nonspecific "noise" signals from excessive wildtype background sequences, esp. under rapid isothermal multiplexed target amplification conditions. Herein, the mol. hybridization chem. between NA bases is manipulated to suppress noise signals and achieve ultraselective multiplexed detection of cancer gene fusion NA variants. Firstly, modified locked NA (LNA) bases are rationally introduced into oligonucleotide sequences as designed "locker probes" for high affinity hybridization to wildtype sequences, leading to enrichment of mutant variants for multiplexed isothermal amplification. Secondly, locker probes are coupled with a customized "proximity-programmed" (SERS) readout which allows precise control of hybridization-based plasmonic signaling to specifically detect multiple target amplicons within a single reaction. Moreover, the use of triple bond Raman reporters endows NA noise signal-free quantification in the Raman silent region (≈1800-2600 cm-1). With this dual mol. hybridization-based strategy, ultraselective multiplexed detection of gene fusion NA variants in cancer cellular models is actualized with successful noise suppression of native wildtype sequences. The distinct benefits of isothermal NA amplification and SERS multiplexing ability are simultaneously harnessed.
- 583Han, X. X.; Zhao, B.; Ozaki, Y. Surface-enhanced Raman scattering for protein detection. Anal. Bioanal. Chem. 2009, 394, 1719– 1727, DOI: 10.1007/s00216-009-2702-3Google Scholar583Surface-enhanced Raman scattering for protein detectionHan, Xiao X.; Zhao, Bing; Ozaki, YukihiroAnalytical and Bioanalytical Chemistry (2009), 394 (7), 1719-1727CODEN: ABCNBP; ISSN:1618-2642. (Springer)A review. Proteins are essential components of organisms and they participate in every process within cells. The key characteristic of proteins that allows their diverse functions is their ability to bind other mols. specifically and tightly. With the development of proteomics, exploring high-efficiency detection methods for large-scale proteins is increasingly important. In recent years, rapid development of surface-enhanced Raman scattering (SERS)-based biosensors leads to the SERS realm of applications from chem. anal. to nanostructure characterization and biomedical applications. For proteins, early studies focused on investigating SERS spectra of individual proteins, and the successful design of nanoparticle probes has promoted great progress of SERS-based immunoassays. In this review we outline the development of SERS-based methods for proteins with particular focus on our proposed protein-mediated SERS-active substrates and their applications in label-free and Raman dye-labeled protein detection.
- 584Han, X. X.; Ozaki, Y.; Zhao, B. Label-free detection in biological applications of surface-enhanced Raman scattering. TrAC Trends in Analytical Chemistry 2012, 38, 67– 78, DOI: 10.1016/j.trac.2012.05.006Google Scholar584Label-free detection in biological applications of surface-enhanced Raman scatteringHan, Xiao Xia; Ozaki, Yukihiro; Zhao, BingTrAC, Trends in Analytical Chemistry (2012), 38 (), 67-78CODEN: TTAEDJ; ISSN:0165-9936. (Elsevier B. V.)A review. Surface-enhanced Raman scattering (SERS) is currently undergoing rapid development as an ultra-sensitive anal. technique in the biol. field. Label-free and extrinsic SERS labeling are two independent approaches that are commonly used to detect biomols. directly and indirectly. The label-free detection method is a direct, convenient method for the detection of biomols. and is more reliable than extrinsic SERS labeling, but its major limitations are poor selectivity in some complex mixts. and poor sensitivity at relatively low sample concns. However, label-free, highly sensitive, selective detection of biomols. based on SERS is possible. With the development of novel SERS-active substrates, Raman instruments, and methods for sample pretreatment, the label-free protocol is becoming increasingly powerful and promising. This review highlights recent developments in label-free SERS-based techniques for bimol. detection, including direct biomol. identification, biomol.-ligand recognition via spectral differences among mol. bridges, and indirect phenolic mol. detection based on azo couplings.
- 585Han, X. X.; Rodriguez, R. S.; Haynes, C. L.; Ozaki, Y.; Zhao, B. Surface-enhanced Raman spectroscopy. Nat. Rev. Methods Primers 2021, 1, 87, DOI: 10.1038/s43586-021-00083-6Google Scholar585Surface-enhanced Raman spectroscopyHan, Xiao Xia; Rodriguez, Rebeca S.; Haynes, Christy L.; Ozaki, Yukihiro; Zhao, BingNature Reviews Methods Primers (2021), 1 (1), 87CODEN: NRMPAT; ISSN:2662-8449. (Nature Portfolio)Surface-enhanced Raman spectroscopy (SERS) is a highly sensitive technique that enhances the Raman scattering of mols. supported by some nanostructured materials. SERS allows for the structural fingerprinting of low-concn. analytes through the plasmon-mediated amplification of elec. fields or chem. enhancement. Owing to its ultra-high sensitivity and selectivity, SERS has a vast array of applications in surface and interface chem., catalysis, nanotechnol., biol., biomedicine, food science, environmental anal. and other areas. This Primer aims to provide interdisciplinary readers with key points regarding SERS methods. We briefly introduce the basic theories of SERS enhancement mechanisms. Details about SERS equipment, SERS-active material prepn. and SERS measurements are summarized, followed by results and typical methods for data anal. Recent applications of SERS in multiple research fields are then highlighted, including probing surface reactions and interfacial charge transfer, structural characterization and chem./biol. sensing. Furthermore, spectral reproducibility, SERS tech. limitations and possible optimizations are discussed to provide readers with methodol. guidance for the rational design of related studies. The Primer ends with a discussion of promising opportunities for SERS-based research in the future.
- 586Han, X. X.; Li, J.; Öner, I. H.; Zhao, B.; Leimkühler, S.; Hildebrandt, P.; Weidinger, I. M. Nickel electrodes as a cheap and versatile platform for studying structure and function of immobilized redox proteins. Anal. Chim. Acta 2016, 941, 35– 40, DOI: 10.1016/j.aca.2016.08.053Google Scholar586Nickel electrodes as a cheap and versatile platform for studying structure and function of immobilized redox proteinsHan, Xiao Xia; Li, Junbo; Oner, Ibrahim Halil; Zhao, Bing; Leimkuhler, Silke; Hildebrandt, Peter; Weidinger, Inez M.Analytica Chimica Acta (2016), 941 (), 35-40CODEN: ACACAM; ISSN:0003-2670. (Elsevier B.V.)Practical use of many bioelectronic and bioanal. devices is limited by the need of expensive materials and time consuming fabrication. Here we demonstrate the use of nickel electrodes as a simple and cheap solid support material for bioelectronic applications. The naturally nanostructured electrodes showed a surprisingly high electromagnetic surface enhancement upon light illumination such that immobilization and electron transfer reactions of the model redox proteins cytochrome b5 (Cyt b5) and cytochrome c (Cyt c) could be followed via surface enhanced resonance Raman spectroscopy. It could be shown that the nickel surface, when used as received, promotes a very efficient binding of the proteins upon preservation of their native structure. The immobilized redox proteins could efficiently exchange electrons with the electrode and could even act as an electron relay between the electrode and solubilized myoglobin. Our results open up new possibility for nickel electrodes as an exceptional good support for bioelectronic devices and biosensors on the one hand and for surface enhanced spectroscopic investigations on the other hand.
- 587Han, X. X.; Schmidt, A. M.; Marten, G.; Fischer, A.; Weidinger, I. M.; Hildebrandt, P. Magnetic silver hybrid nanoparticles for surface-enhanced resonance Raman spectroscopic detection and decontamination of small toxic molecules. ACS Nano 2013, 7, 3212– 20, DOI: 10.1021/nn305892jGoogle Scholar587Magnetic Silver Hybrid Nanoparticles for Surface-Enhanced Resonance Raman Spectroscopic Detection and Decontamination of Small Toxic MoleculesHan, Xiao Xia; Schmidt, Annette M.; Marten, Gernot; Fischer, Anna; Weidinger, Inez M.; Hildebrandt, PeterACS Nano (2013), 7 (4), 3212-3220CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Magnetic hybrid assemblies of Ag and Fe3O4 nanoparticles with biocompatibly immobilized myoglobin (Mb) were designed to detect and capture toxic targets (NO2-, CN-, and H2O2). Mb was covalently attached to chitosan-coated magnetic silver hybrid nanoparticles (M-Ag-C) via glutaraldehyde that serves as a linker for the amine groups of Mb and chitosan. As verified by surface-enhanced resonance Raman (SERR) spectroscopy, this immobilization strategy preserves the native structure of the bound Mb as well as the binding affinity for small mols. On the basis of characteristic spectral markers, binding of NO2-, CN-, and H2O2 could be monitored and quantified, demonstrating the high sensitivity of this approach with detection limits of 1 nM for nitrite, 0.2 μM for cyanide, and 10 nM for H2O2. Owing to the magnetic properties, these particles were collected by an external magnet to achieve an efficient decontamination of the solns. as demonstrated by SERR spectroscopy. Thus, the present approach combines the highly sensitive anal. potential of SERR spectroscopy with an easy approach for decontamination of aq. solns. with potential applications in food and in environmental and medical safety control.
- 588Chen, L.; Tang, J.; Ma, H.; Jin, S.; Xue, X.; Han, X. X.; Jung, Y. M. High-efficiency charge transfer on SERS-active semiconducting K2Ti6O13 nanowires enables direct transition of photoinduced electrons to protein redox centers. Biosens. Bioelectron. 2021, 191, 113452, DOI: 10.1016/j.bios.2021.113452Google Scholar588High-efficiency charge transfer on SERS-active semiconducting K2Ti6O13 nanowires enables direct transition of photoinduced electrons to protein redox centersChen, Lei; Tang, Jinping; Ma, Hao; Jin, Sila; Xue, Xiangxin; Han, Xiao Xia; Jung, Young MeeBiosensors & Bioelectronics (2021), 191 (), 113452CODEN: BBIOE4; ISSN:0956-5663. (Elsevier B.V.)Photoinduced charge transfer (PICT) plays a crucial role in the chem. mechanism of surface-enhanced Raman scattering (SERS), in which small org. mols. are generally used as probes. Herein, semiconducting K2Ti6O13 nanowires (NWs) are synthesized and are found to exhibit high SERS activity probed by 4-mercaptobenzoic acid (4-MBA). D. functional theory (DFT) calcns. reveal high-efficiency CT on the K2Ti6O13 nanowires. Furthermore, PICT on the K2Ti6O13 NWs is for the first time evidenced by a redox protein, cytochrome c (Cyt c). Under optimized exptl. conditions, the transformation of oxidized Cyt c to its reduced state clearly verifies the electron transfer (ET) from the K2Ti6O13 nanowire to the protein. The ET mechanism is explored based on energy levels of semiconductors and mol. dynamics simulations, thus revealing the importance of energy level matching and electron tunneling from the semiconductor surface to the redox center. This study indicates a great potential of multiple-layered K2Ti6O13 NWs in the application of SERS on semiconducting materials and more importantly, it provides a new route for the rational design of protein-semiconductor interfaces for investigating electron transfer processes of redox proteins and biocatalytic reactions.
- 589Li, J.; Cheng, W.; Wang, X.; Zhang, H.; Jin, J.; Ji, W.; Han, X. X.; Zhao, B. Electron Transfer of Cytochrome c on Surface-Enhanced Raman Scattering–Active Substrates: Material Dependence and Biocompatibility. Chem.─Eur. J. 2017, 23, 9034– 9038, DOI: 10.1002/chem.201702307Google Scholar589Electron Transfer of Cytochrome c on Surface-Enhanced Raman Scattering-Active Substrates: Material Dependence and BiocompatibilityLi, Junbo; Cheng, Weina; Wang, Xiaolei; Zhang, Haijing; Jin, Jing; Ji, Wei; Han, Xiao Xia; Zhao, BingChemistry - A European Journal (2017), 23 (38), 9034-9038CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)Surface-enhanced Raman spectroscopy (SERS) represents a powerful approach for studying the structure and reaction of proteins in fundamental and applied sciences. The surface properties of SERS-active materials det. important parameters such as Raman enhancement ability, biocompatibility, and electronic communication between supports and proteins. Here, electron transfer (ET) of Cyt c on noble metals and transition metals is investigated by SERS spectroscopy. The results here indicate that the ET occurs from the reduced state of Cyt c to silver substrate, depending on the laser wavelengths. Nickel and cobalt can directly transfer electrons to the oxidized state of Cyt c, which enables a reductive activity of these transition metal nanoparticles (NPs). This study demonstrates the role of transition metals as electron donors for Cyt c and has proved that the charge transfer theory for SERS is applicable for explanation of the ET between Cyt c and Ag NPs.
- 590Zhang, H.; Kou, Y.; Li, J.; Chen, L.; Mao, Z.; Han, X. X.; Zhao, B.; Ozaki, Y. Nickel Nanowires Combined with Surface-Enhanced Raman Spectroscopy: Application in Label-Free Detection of Cytochrome c-Mediated Apoptosis. Anal. Chem. 2019, 91, 1213– 1216, DOI: 10.1021/acs.analchem.8b04204Google Scholar590Nickel Nanowires Combined with Surface-Enhanced Raman Spectroscopy: Application in Label-Free Detection of Cytochrome c-Mediated ApoptosisZhang, Haijing; Kou, Yiming; Li, Junbo; Chen, Lei; Mao, Zhu; Han, Xiao Xia; Zhao, Bing; Ozaki, YukihiroAnalytical Chemistry (Washington, DC, United States) (2019), 91 (2), 1213-1216CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Intrinsic properties of nickel have enabled its wide applications as an effective catalyst. Nickel nanowires (Ni NWs) as electron donors for oxidized cytochrome c (Cyt c) were studied, which are NW diam., temp., and pH value-dependent. The reductive and magnetic properties facilitate the Ni NWs to rapidly and conveniently reduce Cyt c in complicated biol. samples. Moreover, the Ni NWs combined with resonance Raman spectroscopy have specificity toward Cyt c detection in real biol. samples, which is successfully used to distinguish the redox state of the released Cyt c from isolated mitochondria in apoptotic Hela cells. Moreover, rapid label-free Cyt c quantification can be achieved by surface-enhanced Raman spectroscopy with a limit of detection of 1 nM and long concn. linear range (1 nM-1 μM). The proposed Ni NWs-based redn. approach will significantly simplify the traditional biol. methods and has great potential in the application of Cyt c-related apoptotic studies.
- 591Zhu, J.; Zhu, J.; Xie, H.; Tang, J.; Miao, Y.; Cai, L.; Hildebrandt, P.; Han, X. X. In Situ Raman Spectroscopy Reveals Cytochrome c Redox-Controlled Modulation of Mitochondrial Membrane Permeabilization That Triggers Apoptosis. Nano Lett. 2024, 24, 370– 377, DOI: 10.1021/acs.nanolett.3c04129Google ScholarThere is no corresponding record for this reference.
- 592Zhu, J.; Jiang, M.; Ma, H.; Zhang, H.; Cheng, W.; Li, J.; Cai, L.; Han, X. X.; Zhao, B. Redox-State-Mediated Regulation of Cytochromec Release in Apoptosis Revealed by Surface-Enhanced Raman Scattering on Nickel Substrates. Angew. Chem., Int. Ed. 2019, 58, 16499– 16503, DOI: 10.1002/anie.201909638Google Scholar592Redox-State-Mediated Regulation of Cytochrome c Release in Apoptosis Revealed by Surface-Enhanced Raman Scattering on Nickel SubstratesZhu, Jinyu; Jiang, Muwei; Ma, Hao; Zhang, Haijing; Cheng, Weina; Li, Junbo; Cai, Linjun; Han, Xiao Xia; Zhao, BingAngewandte Chemie, International Edition (2019), 58 (46), 16499-16503CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)The interaction of cytochrome c (Cyt c) with cardiolipin (CL) is believed to play an important role in the initial events of apoptosis. Herein, we investigate the structural changes of CL-bound Fe2+Cyt c and the correlation with Cyt c release through surface-enhanced Raman spectroscopy (SERS) on nickel substrates. The SERS results together with mol. dynamics simulation reveal that Fe2+Cyt c undergoes autoxidn. and a relatively larger conformational alteration after binding with CL, inducing higher peroxidase activity of Cyt c and higher permeability of the CL membrane compared with those induced by the Fe3+Cyt c. The proapoptotic activity and SERS effect of the Ni nanostructures allow the in situ study of the redox-state-dependent Cyt c release from isolated mitochondria, which reveals for the first time that the ferrous state of Cyt c most likely plays a more important role in triggering apoptosis.
- 593Tang, J.; Song, L.; Xie, H.; Zhu, J.; Li, W.; Xu, G.; Cai, L.; Han, X. X. In Situ and Real-Time Monitoring of Mitochondria–Endoplasmic Reticulum Crosstalk in Apoptosis via Surface-Enhanced Resonance Raman Spectroscopy. Nano Lett. 2023, 23, 8363– 8369, DOI: 10.1021/acs.nanolett.3c02764Google Scholar593In Situ and Real-Time Monitoring of Mitochondria-Endoplasmic Reticulum Crosstalk in Apoptosis via Surface-Enhanced Resonance Raman SpectroscopyTang, Jinping; Song, Li; Xie, Han; Zhu, Jinyu; Li, Wei; Xu, Guangyang; Cai, Linjun; Han, Xiao XiaNano Letters (2023), 23 (17), 8363-8369CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)The crosstalk between mitochondria and endoplasmic reticula plays a crucial role in apoptotic pathways in which reactive oxygen species (ROS) produced by microsomal monooxygenase (MMO) are believed to accelerate cytochrome c release. Herein, we successfully demonstrate the potential of surface-enhanced resonance Raman spectroscopy (SERRS) for monitoring MMO-derived ROS formation and ROS-mediated cytochrome c release. Silver nanoparticles coated with nickel shells are used as both Raman signal enhancers and electron donors for cytochrome c. SERRS of cytochrome c is found to be sensitive to ROS, allowing for in situ probing of ROS formation with a cell death inducer. Label-free evaluation of ROS-induced apoptosis is achieved by SERRS-based monitoring of cytochrome c release in living cells. This study verifies the capability of SERRS for label-free, in situ, and real-time monitoring of the mitochondria-endoplasmic reticulum crosstalk in apoptosis and provides a novel strategy for the rational design and screening of ROS-inducing drugs for cancer treatment.
- 594Yang, Y.; Peng, Y.; Lin, C.; Long, L.; Hu, J.; He, J.; Zeng, H.; Huang, Z.; Li, Z.-Y.; Tanemura, M.; Shi, J.; Lombardi, J. R.; Luo, X. Human ACE2-Functionalized Gold ″Virus-Trap″ Nanostructures for Accurate Capture of SARS-CoV-2 and Single-Virus SERS Detection. Nano-micro Lett. 2021, 13, 109– 109, DOI: 10.1007/s40820-021-00620-8Google Scholar594Human ACE2-functionalized gold "virus-trap" nanostructures for accurate capture of SARS-CoV-2 and single-virus SERS detectionYang, Yong; Peng, Yusi; Lin, Chenglong; Long, Li; Hu, Jingying; He, Jun; Zeng, Hui; Huang, Zhengren; Li, Zhi-Yuan; Tanemura, Masaki; Shi, Jianlin; Lombardi, John R.; Luo, XiaoyingNano-Micro Letters (2021), 13 (), 109CODEN: NLAEBV; ISSN:2150-5551. (Nano-Micro Letters)The current COVID-19 pandemic urges the extremely sensitive and prompt detection of SARS-CoV-2 virus. Here, we present a Human Angiotensin-converting-enzyme 2 (ACE2)-functionalized gold "virus traps" nanostructure as an extremely sensitive SERS biosensor, to selectively capture and rapidly detect S-protein expressed coronavirus, such as the current SARS-CoV-2 in the contaminated water, down to the single-virus level. Such a SERS sensor features extraordinary 106-fold virus enrichment originating from high-affinity of ACE2 with S protein as well as "virus-traps" composed of oblique gold nanoneedles, and 109-fold enhancement of Raman signals originating from multi-component SERS efects. Furthermore, the identifcation std. of virus signals is established by machine-learning and identifcation techniques, resulting in an esp. low detection limit of 80 copies mL-1 for the simulated contaminated water by SARS-CoV-2 virus with complex circumstance as short as 5 min, which is of great signifcance for achieving real-time monitoring and early warning of coronavirus. Moreover, here-developed method can be used to establish the identifcation std. for future unknown coronavirus, and immediately enable extremely sensitive and rapid detection of novel virus.
- 595Park, E.; Kim, W.; Guo, S.; Jin, S.; Park, Y.; Park, J.; Yoo, H. S.; Park, J. H.; Jung, Y. M. Highly selective and quantitative in situ monitoring of cell surface proteins by SERS immunoassay system. Biosens. Bioelectron. 2023, 234, 115366, DOI: 10.1016/j.bios.2023.115366Google ScholarThere is no corresponding record for this reference.
- 596Xu, G.; Li, W.; Xie, H.; Zhu, J.; Song, L.; Tang, J.; Miao, Y.; Han, X. X. In Situ Monitoring of Membrane Protein Electron Transfer via Surface-Enhanced Resonance Raman Spectroscopy. Anal. Chem. 2024, 96, 6– 11, DOI: 10.1021/acs.analchem.3c04700Google ScholarThere is no corresponding record for this reference.
- 597Wang, F.; Liu, J. A Stable Lipid/TiO2Interface with Headgroup-Inversed Phosphocholine and a Comparison with SiO2. J. Am. Chem. Soc. 2015, 137, 11736– 11742, DOI: 10.1021/jacs.5b06642Google Scholar597A Stable Lipid/TiO2 Interface with Headgroup-Inversed Phosphocholine and a Comparison with SiO2Wang, Feng; Liu, JuewenJournal of the American Chemical Society (2015), 137 (36), 11736-11742CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Zwitterionic phosphocholine (PC) lipids are highly biocompatible, representing a major component of the cell membrane. A simple mixing of PC liposomes and silica (SiO2) surface results in liposome fusion with the surface and formation of supported lipid bilayers. However, the stability of this bilayer is relatively low because adsorption is based mainly on weak van der Waals force. PC lipids strongly adsorb by TiO2 via chem. bonding with the lipid phosphate. The lack of fusion on TiO2 is attributable to the steric effect from the choline group in PC. Inverse phosphocholine lipids (CP) were used, directly exposing the phosphate. Using a calcein leakage assay and cryo-TEM, fusion of CP liposome with TiO2 is demonstrated. The stability of this supported bilayer is significantly higher than that of the PC/SiO2 system, as indicated by washing the membrane under harsh conditions. Adsorption of CP liposomes by TiO2 is inhibited at high pH. The CP liposome cannot fuse with silica surface because of a strong charge repulsion. This study demonstrates an interesting interplay between a soft matter surface and metal oxides. By tuning the lipid structure, it is possible to rationally control the interaction force. This study provides an alternative system for forming stable supported bilayers on TiO2, and represents the first example of interfacing inverse lipids with inorg. surfaces.
- 598Ma, H.; Tang, X.; Liu, Y.; Han, X. X.; He, C.; Lu, H.; Zhao, B. Surface-Enhanced Raman Scattering for Direct Protein Function Investigation: Controlled Immobilization and Orientation. Anal. Chem. 2019, 91, 8767– 8771, DOI: 10.1021/acs.analchem.9b01956Google Scholar598Surface-Enhanced Raman Scattering for Direct Protein Function Investigation: Controlled Immobilization and OrientationMa, Hao; Tang, Xiaofan; Liu, Yawen; Han, Xiao Xia; He, Chengyan; Lu, Hui; Zhao, BingAnalytical Chemistry (Washington, DC, United States) (2019), 91 (14), 8767-8771CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Surface-enhanced Raman spectroscopy (SERS) has exhibited great potential in protein identification and quantification. However, the poor spectral reproducibility, originating from random protein immobilization on SERS substrates, still makes it challenging for SERS to probe protein functions without any extrinsic Raman labels. Here, in our study, spacer mols. between proteins and SERS substrates are optimized for both biocompatible protein immobilization and Raman scattering enhancement. We have accordingly prepd. iminodiacetic acid (IDA)-functionalized silver substrates, which are used for capturing His-tagged proteins via nickel-imidazole coordination. The controlled immobilization enables excellent SERS spectral reproducibility as evidenced by 6 polypeptides. Furthermore, the interactions between two model proteins, Erv1C (C-terminal domain of FAD-dependent mitochondrial cytochrome c reductase Erv1) and AFP (alpha-fetoprotein), and their ligands Cyt c (cytochrome c) and ATRA (all-trans-retinoic acid) are examd., resp. The results indicate that the IDA-functionalized silver substrates enable controlled protein immobilization and allow label-free protein function investigation by SERS. As a proof-of-concept study, the proposed functionalized SERS-active substrates combined with immobilized metal-affinity chromatog. will be useful for mechanism studies on protein-ligand interactions, which is crucially important for understanding the structural basis of protein functional versatility and will contribute to the fields of drug design and biotechnol.
- 599Abramson, J.; Adler, J.; Dunger, J.; Evans, R.; Green, T.; Pritzel, A.; Ronneberger, O.; Willmore, L.; Ballard, A. J.; Bambrick, J.; Bodenstein, S. W.; Evans, D. A.; Hung, C.-C.; O’Neill, M.; Reiman, D.; Tunyasuvunakool, K.; Wu, Z.; Žemgulytė, A.; Arvaniti, E.; Beattie, C.; Bertolli, O.; Bridgland, A.; Cherepanov, A.; Congreve, M.; Cowen-Rivers, A. I.; Cowie, A.; Figurnov, M.; Fuchs, F. B.; Gladman, H.; Jain, R.; Khan, Y. A.; Low, C. M. R.; Perlin, K.; Potapenko, A.; Savy, P.; Singh, S.; Stecula, A.; Thillaisundaram, A.; Tong, C.; Yakneen, S.; Zhong, E. D.; Zielinski, M.; Žídek, A.; Bapst, V.; Kohli, P.; Jaderberg, M.; Hassabis, D.; Jumper, J. M. Accurate structure prediction of biomolecular interactions with AlphaFold 3. Nature 2024, 630, 493– 500, DOI: 10.1038/s41586-024-07487-wGoogle ScholarThere is no corresponding record for this reference.
- 600Inoue, M.; Ohtaka, K. Surface Enhanced Raman Scattering by Metal Spheres. I. Cluster Effect. J. Phys. Soc. Jpn. 1983, 52, 3853– 3864, DOI: 10.1143/JPSJ.52.3853Google Scholar600Surface enhanced Raman scattering by metal spheres. I. Cluster effectInoue, Masahiro; Ohtaka, KazuoJournal of the Physical Society of Japan (1983), 52 (11), 3853-64CODEN: JUPSAU; ISSN:0031-9015.An electromagnetic theory for the light absorption by a cluster of metal spheres and the Raman scattering by a mol. adsorbed on it is presented, which takes into account the retardation effect exactly, and is applicable to an arbitrary cluster size. The theory was applied to a 2-sphere cluster of Ag and Au. The absorption spectrum is doubly peaked, and the max. enhancement factor of the Raman intensity amts. to 107∼108 when the distance between spheres is decreased. Absorption spectra of 3- and 4-sphere clusters were also calcd., which indicate that the essential features of the exptl. observations are explained by the 2-sphere cluster.
- 601Xu, H.; Bjerneld, E. J.; Käll, M.; Börjesson, L. Spectroscopy of Single Hemoglobin Molecules by Surface Enhanced Raman Scattering. Phys. Rev. Lett. 1999, 83, 4357– 4360, DOI: 10.1103/PhysRevLett.83.4357Google Scholar601Spectroscopy of single hemoglobin molecules by surface enhanced Raman scatteringXu, Hongxing; Bjerneld, Erik J.; Kall, Mikael; Borjesson, LarsPhysical Review Letters (1999), 83 (21), 4357-4360CODEN: PRLTAO; ISSN:0031-9007. (American Physical Society)The detection of mol. vibrations in single Hb protein mols. attached to isolated and immobilized Ag nanoparticles was demonstrated by surface-enhanced Raman scattering (SERS). A comparison between calcn. and expt. indicated that electromagnetic field effects dominated the surface enhancement, and that single mol. Hb SERS was possible only for mols. situated between Ag particles. The vibrational spectra exhibited temporal fluctuations of unknown origin which appeared to be characteristic of the single mol. detection limit.
- 602Wang, P.-S.; Ma, H.; Yan, S.; Lu, X.; Tang, H.; Xi, X.-H.; Peng, X.-H.; Huang, Y.; Bao, Y.-F.; Cao, M.-F.; Wang, H.; Huang, J.; Liu, G.; Wang, X.; Ren, B. Correlation coefficient-directed label-free characterization of native proteins by surface-enhanced Raman spectroscopy. Chemical Science 2022, 13, 13829– 13835, DOI: 10.1039/D2SC04775FGoogle ScholarThere is no corresponding record for this reference.
- 603Brulé, T.; Yockell-Lelièvre, H.; Bouhélier, A.; Margueritat, J.; Markey, L.; Leray, A.; Dereux, A.; Finot, E. Sorting of Enhanced Reference Raman Spectra of a Single Amino Acid Molecule. J. Phys. Chem. C 2014, 118, 17975– 17982, DOI: 10.1021/jp504395cGoogle Scholar603Sorting of Enhanced Reference Raman Spectra of a Single Amino Acid MoleculeBrule, Thibault; Yockell-Lelievre, Helene; Bouhelier, Alexandre; Margueritat, Jeremie; Markey, Laurent; Leray, Aymeric; Dereux, Alain; Finot, EricJournal of Physical Chemistry C (2014), 118 (31), 17975-17982CODEN: JPCCCK; ISSN:1932-7447. (American Chemical Society)In this contribution, we report the identification of the principal ref. Raman spectra of a single cysteine mol. To that purpose, we design an active Surface Enhanced Raman Spectroscopy (SERS) template based on surfactant-less Chebyshev nanoparticles operating in a microfluidic platform. A principal component anal. is obtained from fluctuating spectra to sort the ref. spectra of cysteine. The assignment of Raman bands brings new insight into the conformation of an amino acid adsorbed onto gold nanoparticle.
- 604Jing, C.; Fang, Y. Experimental (SERS) and theoretical (DFT) studies on the adsorption behaviors of l-cysteine on gold/silver nanoparticles. Chem. Phys. 2007, 332, 27– 32, DOI: 10.1016/j.chemphys.2006.11.019Google Scholar604Experimental (SERS) and theoretical (DFT) studies on the adsorption behaviors of L-cysteine on gold/silver nanoparticlesJing, Cuiyu; Fang, YanChemical Physics (2007), 332 (1), 27-32CODEN: CMPHC2; ISSN:0301-0104. (Elsevier B.V.)It is important to apply the surface-enhanced Raman scattering (SERS) spectra and d. functional theory (DFT) to study the interfacial properties of nanoparticles and the adsorption behavior of mols. on the substrates. In the paper, the adsorption behaviors of L-cysteine mols. on gold/silver nanoparticles were studied. It was demonstrated that in gold colloidal soln., L-cysteine mols. were adsorbed in PH conformation and interacted with the gold surface simultaneously through sulfur, NH 3 + and COO- groups. However, in silver colloidal soln. activated by coadsorption of chloride anions, we could see that for most of the L-cysteine mols., the collision of two L-cysteine mols. may lead to the formation of one L-cystine mol. by the S-S bond, and a few of L-cysteine mols. existed as the PH and PN conformations, and the mols. attached to the silver surface via the carboxylate and amino groups. The calcd. Raman frequencies using DFT-B3LYP/6-31++G(d,p) of L-cysteine mol. were in good agreement with exptl. values, which demonstrated that the DFT method can be taken as a very useful tool to assign the Raman band.
- 605Deckert-Gaudig, T.; Rauls, E.; Deckert, V. Aromatic Amino Acid Monolayers Sandwiched between Gold and Silver: A Combined Tip-Enhanced Raman and Theoretical Approach. J. Phys. Chem. C 2010, 114, 7412– 7420, DOI: 10.1021/jp9098045Google Scholar605Aromatic amino acid monolayers sandwiched between gold and silver: A combined tip-enhanced Raman and theoretical approachDeckert-Gaudig, Tanja; Rauls, Eva; Deckert, VolkerJournal of Physical Chemistry C (2010), 114 (16), 7412-7420CODEN: JPCCCK; ISSN:1932-7447. (American Chemical Society)Tip-enhanced Raman scattering (TERS) measurements and theor. calcns. of the arom. amino acids phenylalanine, tyrosine, and tryptophan sandwiched between gold and silver layers are presented and discussed. Atomically flat micrometer-sized gold nanoplates were chosen as substrates and covered with a monolayer of the resp. amino acid. On the basis of spectral data, the carboxylate and amino groups were detd. to be the preferential moieties attached to the metals in the cavity. The exptl. observation of benzene rings oriented parallel to the gold surface and the influence of the silver tip are discussed and compared with theor. calcns. Finally, it is shown that TERS allows a clear distinction between phenylalanine and tryptophan moieties from a mixt. on the substrates; hence, demonstrating the selectivity of the method on the nanometer scale without further need of any labeling techniques.
- 606Królikowska, A.; Cukras, J.; Witkowski, M.; Tymecka, D.; Hernik-Magoń, A.; Misicka, A.; Dzwolak, W. SERS and DFT Study of Noble-Metal-Anchored Cys-Trp/Trp-Cys Dipeptides: Influence of Main-Chain Direction and Terminal Modifications. J. Phys. Chem. C 2020, 124, 7097– 7116, DOI: 10.1021/acs.jpcc.9b10501Google Scholar606SERS and DFT Study of Noble-Metal-Anchored Cys-Trp/Trp-Cys Dipeptides: Influence of Main-Chain Direction and Terminal ModificationsKrolikowska, Agata; Cukras, Janusz; Witkowski, Marcin; Tymecka, Dagmara; Hernik-Magon, Agnieszka; Misicka, Aleksandra; Dzwolak, WojciechJournal of Physical Chemistry C (2020), 124 (13), 7097-7116CODEN: JPCCCK; ISSN:1932-7447. (American Chemical Society)Tiny changes in the covalent structure of a noble-metal-anchored peptide may affect its surface-enhanced Raman scattering (SERS) signature. While SERS spectra of Cys-Trp peptides are dominated by the bands arising from the arom. Trp side chain, a thorough study of the impact of modifications in SERS-silent regions concerning such dipeptides was yet to be performed. Thus, here we conduct an extensive SERS study of a series of Cys- and Trp-contg. dipeptides, varying both the main-chain direction (Cys-Trp/Trp-Cys) and the presence of typical covalent modifications at N- and C-termini (acetylation/amidation). We use three different SERS-active substrates: oxidn.-redn. cycling-roughened silver (Ag ORC), gold (Au ORC), and chem. synthesized colloidal silver nanoparticles (Ag NPs). Interpretation of the exptl. data was aided with d. functional theory (DFT) calcns. Potential energy distribution (PED) anal. was used for the assignment of dipeptide vibrational bands. IR and normal Raman spectra were also examd. to get a complete vibrational anal. This work may be considered the first report on the effect of terminal group modification and reversing the peptide sequence on the adsorptive behavior of dipeptide on silver and gold surface studied by SERS spectroscopy, supported by full vibrational assignment by means of the DFT method.
- 607Vu Nhat, P.; Si, N. T.; Tien, N. T.; Nguyen, M. T. Theoretical Study of the Binding of the Thiol-Containing Cysteine Amino Acid to the Silver Surface Using a Cluster Model. J. Phys. Chem. A 2021, 125, 3244– 3256, DOI: 10.1021/acs.jpca.0c11182Google Scholar607Theoretical Study of the Binding of the Thiol-Containing Cysteine Amino Acid to the Silver Surface Using a Cluster ModelVu Nhat, Pham; Si, Nguyen Thanh; Tien, Nguyen Thanh; Nguyen, Minh ThoJournal of Physical Chemistry A (2021), 125 (16), 3244-3256CODEN: JPCAFH; ISSN:1089-5639. (American Chemical Society)Computational approaches within the framework of d. functional theory (DFT) were employed to elucidate the binding mechanism of the cysteine amino acid on silver nanoparticles using several small silver clusters Agn with n = 2-10 as surface models. The long-range cor. LC-BLYP functional and correlation consistent basis sets cc-pVTZ-PP and cc-pVTZ were used to det. the structural features, energetics, and spectroscopic and electronic properties of the resulting complexes. In vacuum and highly acidic conditions, cysteine mols. prefer to adsorb on silver clusters via their amine group. In aq. soln., the thiolate head turns out to be the most energetically favorable binding site. The cysteine affinity of silver clusters is greatly altered in different conditions, i.e., acidic soln. < vacuum < aq. soln., and is strongly dependent on the cluster size. As compared to free clusters, the frontier orbital energy gap of the ones capped by cysteine is significantly improved, which corresponds to stronger stability, esp. in aq. soln. The anal. of frontier orbitals also reveals that both forward and backward electron donations exhibit comparable contributions to the enhancement of stabilizing interactions. As for an application, a chem. enhancement mechanism of the surface-enhanced Raman scattering (SERS) procedure of cysteine by silver clusters was also analyzed.
- 608Wu, X.; Cañamares, M. V.; Kakoulli, I.; Sanchez-Cortes, S. Chemical Characterization and Molecular Dynamics Simulations of Bufotenine by Surface-Enhanced Raman Scattering (SERS) and Density Functional Theory (DFT). J. Phys. Chem. Lett. 2022, 13, 5831– 5837, DOI: 10.1021/acs.jpclett.2c01300Google ScholarThere is no corresponding record for this reference.
- 609Yao, G.; Huang, Q. DFT and SERS Study of l-Cysteine Adsorption on the Surface of Gold Nanoparticles. J. Phys. Chem. C 2018, 122, 15241– 15251, DOI: 10.1021/acs.jpcc.8b00949Google Scholar609DFT and SERS Study of L-Cysteine Adsorption on the Surface of Gold NanoparticlesYao, Guohua; Huang, QingJournal of Physical Chemistry C (2018), 122 (27), 15241-15251CODEN: JPCCCK; ISSN:1932-7447. (American Chemical Society)Both surface enhanced Raman spectroscopy (SERS) expts. and d. functional theory (DFT) calcns. have been carried out to study the adsorption of cysteine on Au nanoparticle surface. Cysteine is one of the amino acids that have a rotating dihedral angle and several possible adsorption sites, so there could be many possible adsorption conformations. At present, the adsorption conformation of cysteine on the Au surface was not solved, although previous work had explored the conformations based on DFT method, but no explicit exptl. evidence was provided. Nevertheless, the previous work had indicated that the adsorption conformations of some simple rigid mols. on the surface of metal nanoparticles could be identified through SERS exptl. data. Therefore, the authors attempted to figure out the conformation and adsorption sites of the flexible typical amino acid cysteine on Au nanoparticle surface by combining both DFT and SERS methods. The adsorption of cysteine on the surface Au nanoparticle adopted the most predominant configuration in which cysteine chem. interacted with Au cluster through both S and O sites, with cysteine taking the configuration of a gauche position for the protonated amino group and an antiposition for the carboxylate group in the mol.
- 610Wu, D.-Y.; Liu, X.-M.; Huang, Y.-F.; Ren, B.; Xu, X.; Tian, Z.-Q. Surface Catalytic Coupling Reaction of p-Mercaptoaniline Linking to Silver Nanostructures Responsible for Abnormal SERS Enhancement: A DFT Study. J. Phys. Chem. C 2009, 113, 18212– 18222, DOI: 10.1021/jp9050929Google Scholar610Surface Catalytic Coupling Reaction of p-Mercaptoaniline Linking to Silver Nanostructures Responsible for Abnormal SERS Enhancement: A DFT StudyWu, De-Yin; Liu, Xiu-Min; Huang, Yi-Fan; Ren, Bin; Xu, Xin; Tian, Zhong-QunJournal of Physical Chemistry C (2009), 113 (42), 18212-18222CODEN: JPCCCK; ISSN:1932-7447. (American Chemical Society)P-Mercaptoaniline (pMA, it is often called p-aminothiophenol (PATP)) can form self-assembled monolayer (SAM) through its thiol group on metal surfaces. It is also an important surface probe mol. in the surface-enhanced Raman spectroscopy (SERS). More recently, pMA has been used in mol. electronics as a single-mol. conductance wire to link two nanoscale metal leads, constructing a mol. wire junction. When pMA adsorbs on these metal nanostructures and nanogaps, there exhibit strongly detectable surface Raman signals of "non-totally sym." modes. The abnormal enhancement mechanisms proposed in the literature fall into three different categories, i.e., photoinduced charge transfer, tautomerization of benzenoid and quinonoid states, and the charge tunneling enhancement mechanism. Here, we present a novel mechanism to understand the obsd. SERS for pMA adsorbed on silver surfaces. On the basis of our theor. calcns. combined with the reports in literatures, we propose that the pMA mols. adsorbed on nanoscale rough surfaces of noble metals and nanoparticles undergo a catalytic coupling reaction to selectively produce a new surface species p,p'-dimercaptoazobenzene (DMAB), an arom. azo compd., which is responsible for the exptl. obsd. Raman spectra. The present results are important for understanding many pMA-related expts. on noble nanoparticles.
- 611Huang, J.; Wen, J.; Zhou, M.; Ni, S.; Le, W.; Chen, G.; Wei, L.; Zeng, Y.; Qi, D.; Pan, M.; Xu, J.; Wu, Y.; Li, Z.; Feng, Y.; Zhao, Z.; He, Z.; Li, B.; Zhao, S.; Zhang, B.; Xue, P.; He, S.; Fang, K.; Zhao, Y.; Du, K. On-Site Detection of SARS-CoV-2 Antigen by Deep Learning-Based Surface-Enhanced Raman Spectroscopy and Its Biochemical Foundations. Anal. Chem. 2021, 93, 9174– 9182, DOI: 10.1021/acs.analchem.1c01061Google Scholar611On-Site Detection of SARS-CoV-2 Antigen by Deep Learning-Based Surface-Enhanced Raman Spectroscopy and Its Biochemical FoundationsHuang, Jinglin; Wen, Jiaxing; Zhou, Minjie; Ni, Shuang; Le, Wei; Chen, Guo; Wei, Lai; Zeng, Yong; Qi, Daojian; Pan, Ming; Xu, Jianan; Wu, Yan; Li, Zeyu; Feng, Yuliang; Zhao, Zongqing; He, Zhibing; Li, Bo; Zhao, Songnan; Zhang, Baohan; Xue, Peili; He, Shusen; Fang, Kun; Zhao, Yuanyu; Du, KaiAnalytical Chemistry (Washington, DC, United States) (2021), 93 (26), 9174-9182CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)A rapid, on-site, and accurate SARS-CoV-2 detection method is crucial for the prevention and control of the COVID-19 epidemic. However, such an ideal screening technol. has not yet been developed for the diagnosis of SARS-CoV-2. We have developed a deep learning-based surface-enhanced Raman spectroscopy technique for the sensitive, rapid, and on-site detection of the SARS-CoV-2 antigen in the throat swabs or sputum from 30 confirmed COVID-19 patients. A Raman database based on the spike protein of SARS-CoV-2 was established from expts. and theor. calcns. The corresponding biochem. foundation for this method is also discussed. The deep learning model could predict the SARS-CoV-2 antigen with an identification accuracy of 87.7%. These results suggested that this method has great potential for the diagnosis, monitoring, and control of SARS-CoV-2 worldwide.
- 612Chulhai, D. V.; Chen, X.; Jensen, L. Simulating Ensemble-Averaged Surface-Enhanced Raman Scattering. J. Phys. Chem. C 2016, 120, 20833– 20842, DOI: 10.1021/acs.jpcc.6b02159Google Scholar612Simulating Ensemble-Averaged Surface-Enhanced Raman ScatteringChulhai, Dhabih V.; Chen, Xing; Jensen, LasseJournal of Physical Chemistry C (2016), 120 (37), 20833-20842CODEN: JPCCCK; ISSN:1932-7447. (American Chemical Society)The ability to simulate surface-enhanced Raman scattering (SERS) is a vital tool in elucidating the chem. of mols. near the vicinity of plasmonic metal nanoparticles. Typical methods do not include the dynamics of the mol.(s) of interest and are often limited to a single or few mols. Mol. dynamics simulations were combined with the dressed-tensor formalism to simulate the SERS spectra of Ag nanoparticles coated with a full monolayer of pyridine mols. This method allows simulation of the ensemble-averaged SERS spectra of more realistic large scale systems, while accounting for the organization of mols. in the hotspots. Through these simulations, the preferential binding location and orientation of the mols., the choice of electrodynamics method, and the inclusion of field gradient effects influence both the enhancement distribution and the spectral signatures. Both the translational and rotational motions of a pyridine mol. near a nanoparticle junction may be effectively tracked through its SERS spectrum.
- 613Aggarwal, S.; Mondal, S.; Siddhanta, S.; Bharat, E.; Nagamalleswari, E.; Nagaraja, V.; Narayana, C. Divalent Ion-Induced Switch in DNA Cleavage of KpnI Endonuclease Probed through Surface-Enhanced Raman Spectroscopy. J. Phys. Chem. B 2021, 125, 2241– 2250, DOI: 10.1021/acs.jpcb.0c10667Google ScholarThere is no corresponding record for this reference.
- 614Aliaga, A. E.; Ahumada, H.; Sepúlveda, K.; Gomez-Jeria, J. S.; Garrido, C.; Weiss-López, B. E.; Campos-Vallette, M. M. SERS, Molecular Dynamics and Molecular Orbital Studies of the MRKDV Peptide on Silver and Membrane Surfaces. J. Phys. Chem. C 2011, 115, 3982– 3989, DOI: 10.1021/jp1107153Google Scholar614SERS, Molecular Dynamics and Molecular Orbital Studies of the MRKDV Peptide on Silver and Membrane SurfacesAliaga, Alvaro E.; Ahumada, Hernan; Sepulveda, Karen; Gomez-Jeria, Juan S.; Garrido, Carlos; Weiss-Lopez, Boris E.; Campos-Vallette, Marcelo M.Journal of Physical Chemistry C (2011), 115 (10), 3982-3989CODEN: JPCCCK; ISSN:1932-7447. (American Chemical Society)The MRKDV peptide, structurally assocd. with an immunomodulatory protein, was studied using surface enhanced Raman scattering (SERS), mol. dynamics (MD) simulations, and quantum chem. calcns. The SERS spectrum of the MRKDV peptide adsorbed on the silver surface is dominated by signals coming from the guanidinium moiety of the arginine amino acid (R). Guanidinium is the intrinsic probe that drives the orientation of the peptide onto the silver surface. Mol. mechanics and extended Hueckel calcns. of a model of MRKDV interacting with a silver surface support the exptl. results. MD calcns. representing the evolution of the peptide toward a model membrane were also performed. The guanidinium moiety interacts with the phospholipid membrane surface. A hydrophobic C-terminal modification favors the peptide membrane affinity.
- 615Zhu, J.; Jiang, M.; Ma, H.; Zhang, H.; Cheng, W.; Li, J.; Cai, L.; Han, X. X.; Zhao, B. Redox-State-Mediated Regulation of Cytochrome c Release in Apoptosis Revealed by Surface-Enhanced Raman Scattering on Nickel Substrates. Angew. Chem., Int. Ed. 2019, 58, 16499– 16503, DOI: 10.1002/anie.201909638Google Scholar615Redox-State-Mediated Regulation of Cytochrome c Release in Apoptosis Revealed by Surface-Enhanced Raman Scattering on Nickel SubstratesZhu, Jinyu; Jiang, Muwei; Ma, Hao; Zhang, Haijing; Cheng, Weina; Li, Junbo; Cai, Linjun; Han, Xiao Xia; Zhao, BingAngewandte Chemie, International Edition (2019), 58 (46), 16499-16503CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)The interaction of cytochrome c (Cyt c) with cardiolipin (CL) is believed to play an important role in the initial events of apoptosis. Herein, we investigate the structural changes of CL-bound Fe2+Cyt c and the correlation with Cyt c release through surface-enhanced Raman spectroscopy (SERS) on nickel substrates. The SERS results together with mol. dynamics simulation reveal that Fe2+Cyt c undergoes autoxidn. and a relatively larger conformational alteration after binding with CL, inducing higher peroxidase activity of Cyt c and higher permeability of the CL membrane compared with those induced by the Fe3+Cyt c. The proapoptotic activity and SERS effect of the Ni nanostructures allow the in situ study of the redox-state-dependent Cyt c release from isolated mitochondria, which reveals for the first time that the ferrous state of Cyt c most likely plays a more important role in triggering apoptosis.
- 616D’Urso, L.; Condorelli, M.; Puglisi, O.; Tempra, C.; Lolicato, F.; Compagnini, G.; La Rosa, C. Detection and characterization at nM concentration of oligomers formed by hIAPP, Aβ(1–40) and their equimolar mixture using SERS and MD simulations. Phys. Chem. Chem. Phys. 2018, 20, 20588– 20596, DOI: 10.1039/C7CP08552DGoogle Scholar616Detection and characterization at nM concentration of oligomers formed by hIAPP, Aβ(1-40) and their equimolar mixture using SERS and MD simulationsD'Urso, Luisa; Condorelli, Marcello; Puglisi, Orazio; Tempra, Carmelo; Lolicato, Fabio; Compagnini, Giuseppe; La Rosa, CarmeloPhysical Chemistry Chemical Physics (2018), 20 (31), 20588-20596CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)The authors report a structural study on IAPP, Aβ(1-40) and their equimolar mixt. aggregation pathway at nano-molar concn. using the Surface Enhanced Raman Spectroscopy (SERS) effect induced by Ag metal colloids prepd. by laser processes in soln. and mol. dynamics simulations. The data show the ability of Ag NPs coupled with SERS to detect secondary structures of IAPP, Aβ(1-40) and their 1 : 1 molar ratio mixt. in the oligomeric state. The prepn. of Ag colloids shows superior performance with respect to chem. prepd. nano-particles. SERS spectroscopy shows both selectivity and sensitivity in detecting the secondary structures of hIAPP and Aβ(1-40) and to recognize both proteins in their mixt. However, mol. dynamics simulations confirm SERS structural data and the given atomistic details about the structural organization of IAPP and Aβ(1-40) oligomers. The study shows an inhomogeneity in the chem. compn. of IAPP/Aβ(1-40) oligomer aggregates.
- 617Chen, Y.; Cruz-Chu, E. R.; Woodard, J. C.; Gartia, M. R.; Schulten, K.; Liu, L. Electrically Induced Conformational Change of Peptides on Metallic Nanosurfaces. ACS Nano 2012, 6, 8847– 8856, DOI: 10.1021/nn3027408Google Scholar617Electrically Induced Conformational Change of Peptides on Metallic NanosurfacesChen, Yi; Cruz-Chu, Eduardo R.; Woodard, Jaie C.; Gartia, Manas R.; Schulten, Klaus; Liu, LoganACS Nano (2012), 6 (10), 8847-8856CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Surface immobilized biomol. probes are used in many areas of biomedical research, such as genomics, proteomics, immunol., and pathol. Although the structural conformations of small DNA and peptide mols. in free soln. are well studied both theor. and exptl., the conformation of small biomols. bound on surfaces, esp. under the influence of external elec. fields, is poorly understood. Using a combination of mol. dynamics simulation and surface-enhanced Raman spectroscopy, the authors study the external elec. field-induced conformational change of dodecapeptide probes tethered to a nanostructured metallic surface. Surface-tethered peptides with and without phosphorylated tyrosine residues are compared to show that peptide conformational change under elec. field is sensitive to biochem. modification. The authors' study proposes a highly sensitive in vitro nanoscale electrooptical detection and manipulation method for biomol. conformation and charge at bio-nano interfaces.
- 618Karthigeyan, D.; Siddhanta, S.; Kishore, A. H.; Perumal, S. S. R. R.; Ågren, H.; Sudevan, S.; Bhat, A. V.; Balasubramanyam, K.; Subbegowda, R. K.; Kundu, T. K.; Narayana, C. SERS and MD simulation studies of a kinase inhibitor demonstrate the emergence of a potential drug discovery tool. Proc. Natl. Acad. Sci. U. S. A. 2014, 111, 10416– 10421, DOI: 10.1073/pnas.1402695111Google Scholar618SERS and MD simulation studies of a kinase inhibitor demonstrate the emergence of a potential drug discovery toolKarthigeyan, Dhanasekaran; Siddhanta, Soumik; Kishore, Annavarapu Hari; Perumal, Sathya S. R. R.; Agren, Hans; Sudevan, Surabhi; Bhat, Akshay V.; Balasubramanyam, Karanam; Subbegowda, Rangappa Kanchugarakoppal; Kundu, Tapas K.; Narayana, ChandrabhasProceedings of the National Academy of Sciences of the United States of America (2014), 111 (29), 10416-10421CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)The authors demonstrate the use of surface-enhanced Raman spectroscopy (SERS) as an excellent tool for identifying the binding site of small mols. on a therapeutically important protein. As an example, the authors show the specific binding of the common antihypertension drug felodipine to the oncogenic Aurora A kinase protein via hydrogen bonding interactions with Tyr 212 residue to specifically inhibit its activity. Based on SERS studies, mol. docking, mol. dynamics simulation, biochem. assays, and point mutation-based validation, the authors demonstrate the surface-binding mode of this mol. in two similar hydrophobic pockets in the Aurora A kinase. These binding pockets comprise the same unique hydrophobic patches that may aid in distinguishing human Aurora A vs. human Aurora B kinase in vivo. The application of SERS to identify the specific interactions between small mols. and therapeutically important proteins by differentiating competitive and noncompetitive inhibition demonstrates its ability as a complementary technique. The authors also present felodipine as a specific inhibitor for oncogenic Aurora A kinase. Felodipine retards the rate of tumor progression in a xenografted nude mice model. This study reveals a potential surface pocket that may be useful for developing small mols. by selectively targeting the Aurora family kinases.
- 619Kundu, P. P.; Bhowmick, T.; Swapna, G.; Pavan Kumar, G. V.; Nagaraja, V.; Narayana, C. Allosteric Transition Induced by Mg2+ Ion in a Transactivator Monitored by SERS. J. Phys. Chem. B 2014, 118, 5322– 5330, DOI: 10.1021/jp5000733Google Scholar619Allosteric Transition Induced by Mg2+ Ion in a Transactivator Monitored by SERSKundu, Partha P.; Bhowmick, Tuhin; Swapna, Ganduri; Pavan Kumar, G. V.; Nagaraja, Valakunja; Narayana, ChandrabhasJournal of Physical Chemistry B (2014), 118 (20), 5322-5330CODEN: JPCBFK; ISSN:1520-5207. (American Chemical Society)We demonstrate the utility of the surface-enhanced Raman spectroscopy (SERS) to monitor conformational transitions in protein upon ligand binding. The changes in protein's secondary and tertiary structures were monitored using amide and aliph./arom. side chain vibrations. Changes in these bands are suggestive of the stabilization of the secondary and tertiary structure of transcription activator protein C in the presence of Mg2+ ion, whereas the spectral fingerprint remained unaltered in the case of a mutant protein, defective in Mg2+ binding. The importance of the acidic residues in Mg2+ binding, which triggers an overall allosteric transition in the protein, is visualized in the mol. model. The present study thus opens up avenues toward the application of SERS as a potential tool for gaining structural insights into the changes occurring during conformational transitions in proteins.
- 620Matteini, P.; Cottat, M.; Tavanti, F.; Panfilova, E.; Scuderi, M.; Nicotra, G.; Menziani, M. C.; Khlebtsov, N.; de Angelis, M.; Pini, R. Site-Selective Surface-Enhanced Raman Detection of Proteins. ACS Nano 2017, 11, 918– 926, DOI: 10.1021/acsnano.6b07523Google Scholar620Site-Selective Surface-Enhanced Raman Detection of ProteinsMatteini, Paolo; Cottat, Maximilien; Tavanti, Francesco; Panfilova, Elizaveta; Scuderi, Mario; Nicotra, Giuseppe; Menziani, Maria Cristina; Khlebtsov, Nikolai; de Angelis, Marella; Pini, RobertoACS Nano (2017), 11 (1), 918-926CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Strategies for protein detection via surface-enhanced Raman spectroscopy (SERS) currently exploit the formation of randomly generated hot spots at the interfaces of metal colloidal nanoparticles, which are clustered together by intrusive chem. or phys. processes in the presence of the target biomol. The authors propose a different approach based on selective and quant. gathering of protein mols. at regular hot spots generated on the corners of individual silver nanocubes in aq. medium at physiol. pH. Here, the protein, while keeping its native configuration, experiences an intense local E-field, which boosts SERS efficiency and detection sensitivity. Uncontrolled signal fluctuations caused by variable mol. adsorption to different particle areas or inside clustered nanoparticles are circumvented. Advanced electron microscopy analyses and computational simulations outline a strategy relying on a site-selective mechanism with superior Raman signal enhancement, which offers the perspective of highly controlled and reproducible routine SERS detection of proteins.
- 621Ma, H.; Liu, S.; Liu, Y.; Zhu, J.; Han, X. X.; Ozaki, Y.; Zhao, B. In-situ fingerprinting phosphorylated proteins via surface-enhanced Raman spectroscopy: Single-site discrimination of Tau biomarkers in Alzheimer’s disease. Biosens. Bioelectron. 2021, 171, 112748, DOI: 10.1016/j.bios.2020.112748Google Scholar621In-situ fingerprinting phosphorylated proteins via surface-enhanced Raman spectroscopy: Single-site discrimination of Tau biomarkers in Alzheimer's diseaseMa, Hao; Liu, Songlin; Liu, Yawen; Zhu, Jinyu; Han, Xiao Xia; Ozaki, Yukihiro; Zhao, BingBiosensors & Bioelectronics (2021), 171 (), 112748CODEN: BBIOE4; ISSN:0956-5663. (Elsevier B.V.)Protein phosphorylation, a post-translational modification of proteins, is of vital importance in biol. regulation. Highly sensitive and site-specific identification of phosphorylated proteins is a key requirement for unraveling crucial signal transduction pathways relevant to cancers and neurodegenerative disorders. Traditional detection methods, however, suffer from relying on antibodies, labels or fragmentation prior to anal. Here, an antibody- and label-free in situ approach to fingerprint protein phosphorylation was developed based on intrinsic Raman vibrational information of phosphorylated tyrosine, serine, threonine, or histidine residues. Combining surface-enhanced Raman scattering (SERS) spectroscopy and an immobilized-metal affinity strategy, this method is ultrasensitive to discriminate a single-site phosphorylated S396 in a Tau410 protein, an important biomarker in Alzheimer's disease. The binding feasibility of phosphorylated proteins to the modified SERS-active materials is further evidenced by mol. dynamics simulations. This proof-of-concept study paves a new way for the evaluation of site-specific and intact protein phosphorylation in both fundamental mech. investigation and clin. applications.
- 622Aprà, E.; Bhattarai, A.; El-Khoury, P. Z. Gauging Molecular Orientation through Time Domain Simulations of Surface-Enhanced Raman Scattering. J. Phys. Chem. A 2019, 123, 7142– 7147, DOI: 10.1021/acs.jpca.9b06182Google Scholar622Gauging Molecular Orientation through Time Domain Simulations of Surface-Enhanced Raman ScatteringApra, Edoardo; Bhattarai, Ashish; El-Khoury, Patrick Z.Journal of Physical Chemistry A (2019), 123 (32), 7142-7147CODEN: JPCAFH; ISSN:1089-5639. (American Chemical Society)Mol. reorientation dynamics modulate the phys. and chem. properties of mols. at interfaces. This is particularly the case for org. mols. interacting with metallic surfaces-structural motifs of current interest to ultrasensitive chem./biol. detection/imaging. In this context, surface-enhanced Raman scattering (SERS) can be used to gauge the orientation of mols. in the immediate vicinity of plasmonic metals. Herein , we analyze SERS spectra of two arom. thiols (4-mercaptobenzonitrile and thiophenol) chemisorbed onto silver substrates using ab initio mol. dynamics-based Raman spectral simulations that account for the optical response of mols. in the bulk and oriented mols. at the surface. Through a comparison with prior works aimed at gauging the orientation of our two model systems on metallic substrates, we describe the advantages and discuss the limitations of our described models and approach to gauging the orientation of mols. on metals through time domain simulations of their SERS signatures.
- 623Mullin, J.; Valley, N.; Blaber, M. G.; Schatz, G. C. Combined Quantum Mechanics (TDDFT) and Classical Electrodynamics (Mie Theory) Methods for Calculating Surface Enhanced Raman and Hyper-Raman Spectra. J. Phys. Chem. A 2012, 116, 9574– 9581, DOI: 10.1021/jp307003pGoogle Scholar623Combined Quantum Mechanics (TDDFT) and Classical Electrodynamics (Mie Theory) Methods for Calculating Surface Enhanced Raman and Hyper-Raman SpectraMullin, Jonathan; Valley, Nicholas; Blaber, Martin G.; Schatz, George C.Journal of Physical Chemistry A (2012), 116 (38), 9574-9581CODEN: JPCAFH; ISSN:1089-5639. (American Chemical Society)Multiscale models that combine quantum mechanics and classical electrodynamics are presented, which allow for the evaluation of surface-enhanced Raman (SERS) and hyper-Raman scattering spectra (SEHRS) for both chem. (CHEM) and electrodynamic (EM) enhancement mechanisms. In these models, time-dependent d. functional theory (TDDFT) for a system consisting of the adsorbed mol. and a metal cluster fragment of the metal particle is coupled to Mie theory for the metal particle, with the surface of the cluster being overlaid with the surface of the metal particle. In model A, the electromagnetic enhancement from plasmon-excitation of the metal particle is combined with the chem. enhancement assocd. with a static treatment of the mol.-metal structure to det. overall spectra. In model B, the frequency dependence of the Raman spectrum of the isolated mol. is combined with the enhancements detd. in model A to refine the enhancement est. An equivalent theory at the level of model A is developed for hyper-Raman spectra calcns. Application to pyridine interacting with a 20. nm diam. Ag sphere is presented, including comparisons with an earlier model (denoted G), which combines plasmon enhanced fields with gas-phase Raman (or hyper-Raman) spectra. The EM enhancement factor for spherical particles at 357 nm is 104 and 106 for SERS and SEHRS, resp. Including both chem. and electromagnetic mechanisms at the level of model A leads to enhancements ∼104 and 109 for SERS and SEHRS.
- 624Mullin, J.; Schatz, G. C. Combined Linear Response Quantum Mechanics and Classical Electrodynamics (QM/ED) Method for the Calculation of Surface-Enhanced Raman Spectra. J. Phys. Chem. A 2012, 116, 1931– 1938, DOI: 10.1021/jp2087829Google Scholar624Combined Linear Response Quantum Mechanics and Classical Electrodynamics (QM/ED) Method for the Calculation of Surface-Enhanced Raman SpectraMullin, Jonathan; Schatz, George C.Journal of Physical Chemistry A (2012), 116 (8), 1931-1938CODEN: JPCAFH; ISSN:1089-5639. (American Chemical Society)A multiscale method is presented that allows for evaluation of plasmon-enhanced optical properties of nanoparticle/mol. complexes with no addnl. cost compared to std. electrodynamics (ED) and linear response quantum mechanics (QM) calcns. for the particle and mol., resp., but with polarization and orientation effects automatically described. The approach 1st calcs. the total field of the nanoparticle by ED using the finite difference time domain (FDTD) method. The field intensity in the frequency domain as a function of distance from the nanoparticle is calcd. via a Fourier transform. The mol. optical properties are then calcd. with QM in the frequency domain in the presence of the total field of the nanoparticle. Back-coupling due to dipolar reradiation effects is included in the single-mol. plane wave approxn. The effects of polarization and partial orientation averaging are considered. The QM/ED method is evaluated for the well-characterized test case of surface-enhanced Raman scattering (SERS) of pyridine bound to Ag, as well as for the resonant Raman chromophore rhodamine 6G. The electromagnetic contribution to the enhancement factor is 104 for pyridine and 102 for rhodamine 6G.
- 625Banik, M.; El-Khoury, P. Z.; Nag, A.; Rodriguez-Perez, A.; Guarrottxena, N.; Bazan, G. C.; Apkarian, V. A. Surface-Enhanced Raman Trajectories on a Nano-Dumbbell: Transition from Field to Charge Transfer Plasmons as the Spheres Fuse. ACS Nano 2012, 6, 10343– 10354, DOI: 10.1021/nn304277nGoogle Scholar625Surface-Enhanced Raman Trajectories on a Nano-Dumbbell: Transition from Field to Charge Transfer Plasmons as the Spheres FuseBanik, Mayukh; El-Khoury, Patrick Z.; Nag, Amit; Rodriguez-Perez, Alejandro; Guarrottxena, Nekane; Bazan, Guillermo C.; Apkarian, Vartkess A.ACS Nano (2012), 6 (11), 10343-10354CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)By taking advantage of the tensor nature of surface-enhanced Raman scattering (SERS), the authors track trajectories of the linker mol. and a CO mol. chemisorbed at the hot spot of a nano-dumbbell consisting of dibenzyldithio-linked Ag nanospheres. The linear Stark shift of CO serves as an abs. gauge of the local field, while the polyat. spectra characterize the vector components of the local field. The authors identify surface-enhanced Raman optical activity due to a transient asperity in the nanojunction in an otherwise uneventful SERS trajectory. During fusion of the spheres, the authors observe sequential evolution of the enhanced spectra from dipole-coupled Raman to quadrupole- and magnetic dipole-coupled Raman, followed by a transition from line spectra to band spectra, and the full reversal of the sequence. From the spectrum of CO, the sequence can be understood to track the evolution of the junction plasmon resonance from dipolar to quadrupolar to charge transfer as a function of intersphere sepn., which evolves at a speed of ∼1 Å/min. The crossover to the conduction limit is marked by the transition of line spectra to Stark-broadened and shifted band spectra. As the junction closes on CO, the local field reaches 1 V/Å, limited to a current of 1 electron per vibrational cycle passing through the mol., with assocd. Raman enhancement factor via the charge transfer plasmon resonance of 1012. The local field identifies that a sharp protrusion is responsible for room-temp. chemisorption of CO on Ag. The asym. phototunneling junction, Ag-CO-Ag, driven by the frequency-tunable charge transfer plasmon of the dumbbell antenna, combines the design elements of an ideal rectifying photocollector.
- 626Ma, H.; Yan, S.; Lu, X.; Bao, Y.-F.; Liu, J.; Liao, L.; Dai, K.; Cao, M.; Zhao, X.; Yan, H.; Wang, H.-L.; Peng, X.; Chen, N.; Feng, H.; Zhu, L.; Yao, G.; Fan, C.; Wu, D.-Y.; Wang, B.; Wang, X.; Ren, B. Rapidly determining the 3D structure of proteins by surface-enhanced Raman spectroscopy. Science Advances 2023, 9, eadh8362, DOI: 10.1126/sciadv.adh8362Google ScholarThere is no corresponding record for this reference.
- 627Hu, W.; Ye, S.; Zhang, Y.; Li, T.; Zhang, G.; Luo, Y.; Mukamel, S.; Jiang, J. Machine Learning Protocol for Surface-Enhanced Raman Spectroscopy. J. Phys. Chem. Lett. 2019, 10, 6026– 6031, DOI: 10.1021/acs.jpclett.9b02517Google Scholar627Machine Learning Protocol for Surface-Enhanced Raman SpectroscopyHu, Wei; Ye, Sheng; Zhang, Yujin; Li, Tianduo; Zhang, Guozhen; Luo, Yi; Mukamel, Shaul; Jiang, JunJournal of Physical Chemistry Letters (2019), 10 (20), 6026-6031CODEN: JPCLCD; ISSN:1948-7185. (American Chemical Society)Surface-enhanced Raman spectroscopy (SERS) is a powerful technique that can capture the electronic-vibrational fingerprint of mols. on surfaces. Ab initio prediction of Raman response is a long-standing challenge because of the diversified interfacial structures. A cost-effective machine learning (ML) random forest method can predict SERS signals of a trans-1,2-bis(4-pyridyl)ethylene (BPE) mol. adsorbed on a Au substrate. Using geometric descriptors extd. from quantum chem. simulations of thousands of ab initio mol. dynamics conformations, the ML protocol predicts vibrational frequencies and Raman intensities. The resulting spectra agree with d. functional theory calcns. and expt. Predicted SERS responses of the mol. on different surfaces, or under external fields of elec. fields and solvent environment, demonstrate the good transferability of the protocol.
- 628Granato, T.; Porpora, M. G.; Longo, F.; Angeloni, A.; Manganaro, L.; Anastasi, E. HE4 in the differential diagnosis of ovarian masses. Clin. Chim. Acta 2015, 446, 147– 155, DOI: 10.1016/j.cca.2015.03.047Google ScholarThere is no corresponding record for this reference.
- 629Gallo, V.; Lai, A.; Pasquo, A.; Almaviva, S.; Iacobelli, S.; Persichetti, L.; Capellini, G.; Antonini, G. Surface-enhanced Raman scattering (SERS)–based immunosystem for ultrasensitive detection of the 90K biomarker. Anal. Bioanal. Chem. 2020, 412, 7659– 7667, DOI: 10.1007/s00216-020-02903-2Google ScholarThere is no corresponding record for this reference.
- 630Muhammad, M.; Shao, C.-s.; Huang, Q. Aptamer-functionalized Au nanoparticles array as the effective SERS biosensor for label-free detection of interleukin-6 in serum. Sens. Actuators B Chem. 2021, 334, 129607, DOI: 10.1016/j.snb.2021.129607Google Scholar630Aptamer-functionalized Au nanoparticles array as the effective SERS biosensor for label-free detection of interleukin-6 in serumMuhammad, Muhammad; Shao, Chang-sheng; Huang, QingSensors and Actuators, B: Chemical (2021), 334 (), 129607CODEN: SABCEB; ISSN:0925-4005. (Elsevier B.V.)A label-free, highly sensitive, and selective biosensor for detection of interleukin-6 (IL-6), which is an important inflammatory and cancer progression cytokine, has been achieved by combining gold nanoparticles (NPs) array surface-enhanced Raman spectroscopy (SERS) substrate and DNA aptamer. The SERS substrate consisted of Au NPs array is functionalized with the aptamer which is composed of the IL-6 recognition sequence and the output signal reporter. Upon recognition of target IL-6 in serum, the aptamer changes its conformation, resulting in the corresponding change of the output Raman intensity ratio (I660/I736), with which the quant. evaluation of IL-6 in 10-12-10-7 M range can be realized. This SERS approach was employed to detect IL-6 in mice serum for inspecting the effect of drug and bacterial infection, and particularly, the radiation injury in the treated animals. This work therefore exemplifies that the aptamer-based SERS biosensor can serve as a promising tool for quick and convenient medical diagnosis applications.
- 631Li, J.; Wuethrich, A.; Sina, A. A. I.; Cheng, H. H.; Wang, Y.; Behren, A.; Mainwaring, P. N.; Trau, M. A digital single-molecule nanopillar SERS platform for predicting and monitoring immune toxicities in immunotherapy. Nat. Commun. 2021, 12, 1087, DOI: 10.1038/s41467-021-21431-wGoogle Scholar631A digital single-molecule nanopillar SERS platform for predicting and monitoring immune toxicities in immunotherapyLi, Junrong; Wuethrich, Alain; Sina, Abu A. I.; Cheng, Han-Hao; Wang, Yuling; Behren, Andreas; Mainwaring, Paul N.; Trau, MattNature Communications (2021), 12 (1), 1087CODEN: NCAOBW; ISSN:2041-1723. (Nature Research)The introduction of immune checkpoint inhibitors has demonstrated significant improvements in survival for subsets of cancer patients. However, they carry significant and sometimes life-threatening toxicities. Prompt prediction and monitoring of immune toxicities have the potential to maximise the benefits of immune checkpoint therapy. Herein, we develop a digital nanopillar SERS platform that achieves real-time single cytokine counting and enables dynamic tracking of immune toxicities in cancer patients receiving immune checkpoint inhibitor treatment - broader applications are anticipated in other disease indications. By analyzing four prospective cytokine biomarkers that initiate inflammatory responses, the digital nanopillar SERS assay achieves both highly specific and highly sensitive cytokine detection down to attomolar level. Significantly, we report the capability of the assay to longitudinally monitor 10 melanoma patients during immune inhibitor blockade treatment. Here, we show that elevated cytokine concns. predict for higher risk of developing severe immune toxicities in our pilot cohort of patients.
- 632Lee, H.; Kim, W.; Song, M. Y.; Kim, D. H.; Jung, H. S.; Kim, W.; Choi, S. One-Stop Plasmonic Nanocube-Excited SERS Immunoassay Platform of Multiple Cardiac Biomarkers for Rapid Screening and Progressive Tracing of Acute Myocardial Infarction. Small 2024, 20, 2304999, DOI: 10.1002/smll.202304999Google ScholarThere is no corresponding record for this reference.
- 633Ouyang, Y.; Xie, W.; Tang, T.; Su, X.; Xiao, S.; Liu, Z.; Li, M.; Wu, M.; Liu, J.; Luo, J.; Chen, P. Quantitative SERS detection of serum protein biomarkers for assessment of tumor microwave ablation outcomes. Chemical Engineering Journal 2024, 496, 154004, DOI: 10.1016/j.cej.2024.154004Google ScholarThere is no corresponding record for this reference.
- 634Su, X.; Liu, X.; Ouyang, Y.; Xie, Y.; Chen, M.; Chen, P.; Liu, J.; Wu, M.; Lin, C.-h.; Zhong, H.; Li, M. SERS lateral flow strip detection of serum biomarkers for noninvasive assessment of operative microwave ablation outcomes of unresectable hepatocellular carcinoma. Chemical Engineering Journal 2024, 485, 149833, DOI: 10.1016/j.cej.2024.149833Google ScholarThere is no corresponding record for this reference.
- 635Gao, X.; Boryczka, J.; Zheng, P.; Kasani, S.; Yang, F.; Engler-Chiurazzi, E. B.; Simpkins, J. W.; Wigginton, J. G.; Wu, N. A “hot Spot”-Enhanced paper lateral flow assay for ultrasensitive detection of traumatic brain injury biomarker S-100β in blood plasma. Biosens. Bioelectron. 2021, 177, 112967, DOI: 10.1016/j.bios.2021.112967Google Scholar635A "hot Spot"-Enhanced paper lateral flow assay for ultrasensitive detection of traumatic brain injury biomarker S-100β in blood plasmaGao, Xuefei; Boryczka, Jennifer; Zheng, Peng; Kasani, Sujan; Yang, Feng; Engler-Chiurazzi, Elizabeth B.; Simpkins, James W.; Wigginton, Jane G.; Wu, NianqiangBiosensors & Bioelectronics (2021), 177 (), 112967CODEN: BBIOE4; ISSN:0956-5663. (Elsevier B.V.)Currently colorimetric paper lateral flow strips (PLFS) encounter two major limitations, i.e., low sensitivity and severe interference from complex sample matrixes such as blood. These shortcomings limit their application in detection of low-concn. analytes in complex samples. To solve these problems, a PLFS has been developed by utilizing surface-enhanced Raman scattering (SERS) for sensing signal transduction. In particular, a hierarchical three-dimensional nanostructure has been designed to create "hot spots", which can significantly amplify the SERS sensing signal, leading to high sensitivity. As a result, this PLFS has demonstrated a limit of detection (LOD) of 5.0 pg mL-1 toward detection of S-100β, a traumatic brain injury (TBI) protein biomarker in blood plasma. The PLFS has been successfully used for rapid measurement of S-100β in clin. TBI patient samples taken in the emergency department. Availability of PLFS for blood testing would shift the paradigm of TBI patient management and clin. outcome in emergency departments. It is expected that this type of PLFS can be adapted for rapid detection of various human diseases due to its capability of measuring a low level of protein blood biomarkers in complex human fluids.
- 636Fan, M.; Li, Y.; Chen, J.; Lin, Y.; Lai, S.; Peng, S.; Lin, D.; Wang, J.; Lu, Y.; Feng, S. Plasmonic internal standard-decorated nitrocellulose membranes for duplex detection of circulating tumor biomarkers. Sens. Actuators B Chem. 2023, 395, 134508, DOI: 10.1016/j.snb.2023.134508Google ScholarThere is no corresponding record for this reference.
- 637Lu, D.; Ran, M.; Liu, Y.; Xia, J.; Bi, L.; Cao, X. SERS spectroscopy using Au-Ag nanoshuttles and hydrophobic paper-based Au nanoflower substrate for simultaneous detection of dual cervical cancer–associated serum biomarkers. Anal. Bioanal. Chem. 2020, 412, 7099– 7112, DOI: 10.1007/s00216-020-02843-xGoogle ScholarThere is no corresponding record for this reference.
- 638Cao, X.; Liu, Z.; Qin, X.; Gu, Y.; Huang, Y.; Qian, Y.; Wang, Z.; Li, H.; Zhu, Q.; Wei, W. LoC-SERS platform for rapid and sensitive detection of colorectal cancer protein biomarkers. Talanta 2024, 270, 125563, DOI: 10.1016/j.talanta.2023.125563Google ScholarThere is no corresponding record for this reference.
- 639Plou, J.; Valera, P. S.; García, I.; de Albuquerque, C. D. L.; Carracedo, A.; Liz-Marzán, L. M. Prospects of Surface-Enhanced Raman Spectroscopy for Biomarker Monitoring toward Precision Medicine. ACS Photonics 2022, 9, 333– 350, DOI: 10.1021/acsphotonics.1c01934Google Scholar639Prospects of Surface-Enhanced Raman Spectroscopy for Biomarker Monitoring toward Precision MedicinePlou, Javier; Valera, Pablo S.; Garcia, Isabel; de Albuquerque, Carlos D. L.; Carracedo, Arkaitz; Liz-Marzan, Luis M.ACS Photonics (2022), 9 (2), 333-350CODEN: APCHD5; ISSN:2330-4022. (American Chemical Society)Future precision medicine will be undoubtedly sustained by the detection of validated biomarkers that enable a precise classification of patients based on their predicted disease risk, prognosis, and response to a specific treatment. Up to now, genomics, transcriptomics, and immunohistochem. have been the main clin. amenable tools at hand for identifying key diagnostic, prognostic, and predictive biomarkers. However, other mol. strategies, including metabolomics, are still in their infancy and require the development of new biomarker detection technologies, toward routine implementation into clin. diagnosis. In this context, surface-enhanced Raman scattering (SERS) spectroscopy has been recognized as a promising technol. for clin. monitoring thanks to its high sensitivity and label-free operation, which should help accelerate the discovery of biomarkers and their corresponding screening in a simpler, faster, and less-expensive manner. Many studies have demonstrated the excellent performance of SERS in biomedical applications. However, such studies have also revealed several variables that should be considered for accurate SERS monitoring, in particular, when the signal is collected from biol. sources (tissues, cells or biofluids). This Perspective is aimed at piecing together the puzzle of SERS in biomarker monitoring, with a view on future challenges and implications. We address the most relevant requirements of plasmonic substrates for biomedical applications, as well as the implementation of tools from artificial intelligence or biotechnol. to guide the development of highly versatile sensors.
- 640Frantz, C.; Stewart, K. M.; Weaver, V. M. The extracellular matrix at a glance. J. Cell Sci. 2010, 123, 4195– 4200, DOI: 10.1242/jcs.023820Google Scholar640The extracellular matrix at a glanceFrantz, Christian; Stewart, Kathleen M.; Weaver, Valerie M.Journal of Cell Science (2010), 123 (24), 4195-4200CODEN: JNCSAI; ISSN:0021-9533. (Company of Biologists Ltd.)A review describes the main mol. components of the extracellular matrix (ECM) and then compares and contrasts the ECM within a normal simple epithelial tissue with that found within a pathol. modified tissue, as exemplified in aged tissue, wounded or fibrotic tissue and tumors. It focuses on the compn. and architecture of the ECM and interactions with its cellular constituents, and describe in detail common post- translational modifications that evoke defined topol. and viscoelasticity changes in the tissue. It also discusses the functional consequences of RM remodeling on cellular behaviors including altered growth factor sensitivity elicited by changes in ECM tension. It also discusses interstitial stroma of simple glandular epithelial tissues. A brief discussion on application of natural and synthetic ECMs that can be used to either recapitulate the interstitial ECM in culture to study tissue behaviors or to deconstruct and analyze how specific ECM parameters (stiffness, fiber orientation, ligand presentation. dimensionality) provoke specific cellular behaviors is also given.
- 641Prieto-García, E.; Díaz-García, C. V.; García-Ruiz, I.; Agulló-Ortuño, M. T. Epithelial-to-mesenchymal transition in tumor progression. Med. Oncol. 2017, 34, 122, DOI: 10.1007/s12032-017-0980-8Google ScholarThere is no corresponding record for this reference.
- 642Basson, C.; Serem, J. C.; Hlophe, Y. N.; Bipath, P. The tryptophan–kynurenine pathway in immunomodulation and cancer metastasis. Cancer Med. 2023, 12, 18691– 18701, DOI: 10.1002/cam4.6484Google ScholarThere is no corresponding record for this reference.
- 643Plou, J.; García, I.; Charconnet, M.; Astobiza, I.; García-Astrain, C.; Matricardi, C.; Mihi, A.; Carracedo, A.; Liz-Marzán, L. M. Multiplex SERS Detection of Metabolic Alterations in Tumor Extracellular Media. Adv. Funct. Mater. 2020, 30, 1910335, DOI: 10.1002/adfm.201910335Google Scholar643Multiplex SERS Detection of Metabolic Alterations in Tumor Extracellular MediaPlou, Javier; Garcia, Isabel; Charconnet, Mathias; Astobiza, Ianire; Garcia-Astrain, Clara; Matricardi, Cristiano; Mihi, Agustin; Carracedo, Arkaitz; Liz-Marzan, Luis M.Advanced Functional Materials (2020), 30 (17), 1910335CODEN: AFMDC6; ISSN:1616-301X. (Wiley-VCH Verlag GmbH & Co. KGaA)The compn. and intercellular interactions of tumor cells in the tissues dictate the biochem. and metabolic properties of the tumor microenvironment. The metabolic rewiring has a profound impact on the properties of the microenvironment, to an extent that monitoring such perturbations could harbor diagnostic and therapeutic relevance. A growing interest in these phenomena has inspired the development of novel technologies with sufficient sensitivity and resoln. to monitor metabolic alterations in the tumor microenvironment. In this context, surface-enhanced Raman scattering (SERS) can be used for the label-free detection and imaging of diverse mols. of interest among extracellular components. Herein, the application of nanostructured plasmonic substrates comprising Au nanoparticles, self-assembled as ordered superlattices, to the precise SERS detection of selected tumor metabolites, is presented. The potential of this technol. is first demonstrated through the anal. of kynurenine, a secreted immunomodulatory deriv. of the tumor metab. and the related mols. tryptophan and purine derivs. SERS facilitates the unambiguous identification of trace metabolites and allows the multiplex detection of their characteristic fingerprints under different conditions. Finally, the effective plasmonic SERS substrate is combined with a hydrogel-based three-dimensional cancer model, which recreates the tumor microenvironment, for the real-time imaging of metabolite alterations and cytotoxic effects on tumor cells.
- 644Mahmoudi, M.; Lohse, S. E.; Murphy, C. J.; Fathizadeh, A.; Montazeri, A.; Suslick, K. S. Variation of Protein Corona Composition of Gold Nanoparticles Following Plasmonic Heating. Nano Lett. 2014, 14 (1), 6– 12, DOI: 10.1021/nl403419eGoogle Scholar644Variation of Protein Corona Composition of Gold Nanoparticles Following Plasmonic HeatingMahmoudi, Morteza; Lohse, Samuel E.; Murphy, Catherine J.; Fathizadeh, Arman; Montazeri, Abbas; Suslick, Kenneth S.Nano Letters (2014), 14 (1), 6-12CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)It is well recognized that the primary interaction of most biol. environments with nanoparticles (NPs) is strongly influenced by a long-lived ("hard") protein corona that surrounds the NP and remains strongly adsorbed to its surface. The amt. and compn. of assocd. proteins in the corona adsorbed onto the NPs is related to several important factors, including the physicochem. properties of the NPs and the compn. of the protein soln. Here, for the first time, it is shown that plasmonic heat induction (by laser activation) leads to significant changes in the compn. of the hard protein corona adsorbed on low aspect ratio gold nanorods. Using mass spectrometry, several proteins in the corona were identified whose concns. change most substantially as a result of photoinduced (plasmonic) heating vs. simple thermal heating. Mol. modeling suggests that the origin of these changes in protein adsorption may be the result of protein conformational changes in response to much higher local temps. that occur near the gold nanorods during photoinduced, plasmonic heating. These results may define new applications in vivo for NPs with hyperthermia capability and better define the likely interactions of cells with NPs after plasmonic heating. Potential changes in the protein corona following hyperthermia treatment may influence the final biol. fate of plasmonic NPs in clin. applications and help elucidate safety considerations for hyperthermia applications.
- 645Plou, J.; Valera, P. S.; García, I.; Vila-Liarte, D.; Renero-Lecuna, C.; Ruiz-Cabello, J.; Carracedo, A.; Liz-Marzán, L. M. Machine Learning-Assisted High-Throughput SERS Classification of Cell Secretomes. Small 2023, 19, 2207658, DOI: 10.1002/smll.202207658Google Scholar645Machine Learning-Assisted High-Throughput SERS Classification of Cell SecretomesPlou, Javier; Valera, Pablo S.; Garcia, Isabel; Vila-Liarte, David; Renero-Lecuna, Carlos; Ruiz-Cabello, Jesus; Carracedo, Arkaitz; Liz-Marzan, Luis M.Small (2023), 19 (51), 2207658CODEN: SMALBC; ISSN:1613-6810. (Wiley-VCH Verlag GmbH & Co. KGaA)During the response to different stress conditions, damaged cells react in multiple ways, including the release of a diverse cocktail of metabolites. Moreover, secretomes from dying cells can contribute to the effectiveness of anticancer therapies and can be exploited as predictive biomarkers. The nature of the stress and the resulting intracellular responses are key determinants of the secretome compn., but monitoring such processes remains tech. arduous. Hence, there is growing interest in developing tools for noninvasive secretome screening. In this regard, it has been previously shown that the relative concns. of relevant metabolites can be traced by surface-enhanced Raman scattering (SERS), thereby allowing label-free biofluid interrogation. However, conventional SERS approaches are insufficient to tackle the requirements imposed by high-throughput modalities, namely fast data acquisition and automatized anal. Therefore, machine learning methods were implemented to identify cell secretome variations while extg. std. features for cell death classification. To this end, ad hoc microfluidic chips were devised, to readily conduct SERS measurements through a prototype relying on capillary pumps made of filter paper, which eventually would function as the SERS substrates. The developed strategy may pave the way toward a faster implementation of SERS into cell secretome classification, which can be extended even to labs. lacking highly specialized facilities.
- 646Valera, P. S.; Henriques-Pereira, M.; Wagner, M.; Gaspar, V. M.; Mano, J. F.; Liz-Marzán, L. M. Surface-Enhanced Raman Scattering Monitoring of Tryptophan Dynamics in 3D Pancreatic Tumor Models. ACS Sens. 2024, 9, 4236– 4247, DOI: 10.1021/acssensors.4c01210Google ScholarThere is no corresponding record for this reference.
- 647Bi, X.; Ma, B.; Liu, W.; Gao, W.-Q.; Ye, J.; Rao, H. Transcriptome-Aligned Metabolic Profiling by SERSome Reflects Biological Changes Following Mesenchymal Stem Cells Expansion. Stem Cell Res Ther 2024, 15, 467, DOI: 10.1186/s13287-024-04109-0Google ScholarThere is no corresponding record for this reference.
- 648Bi, X.; Wang, J.; Xue, B.; He, C.; Liu, F.; Chen, H.; Lin, L. L.; Dong, B.; Li, B.; Jin, C.; Pan, J.; Xue, W.; Ye, J. SERSomes for metabolic phenotyping and prostate cancer diagnosis. Cell Reports Medicine 2024, 5, 101579, DOI: 10.1016/j.xcrm.2024.101579Google ScholarThere is no corresponding record for this reference.
- 649Liu, F.; Wu, T.; Tian, A.; He, C.; Bi, X.; Lu, Y.; Yang, K.; Xia, W.; Ye, J. Intracellular metabolic profiling of drug resistant cells by surface enhanced Raman scattering. Anal. Chim. Acta 2023, 1279, 341809, DOI: 10.1016/j.aca.2023.341809Google ScholarThere is no corresponding record for this reference.
- 650Liu, F.; Liu, J.; Luo, Y.; Wu, S.; Liu, X.; Chen, H.; Luo, Z.; Yuan, H.; Shen, F.; Zhu, F.; Ye, J. A Single-Cell Metabolic Profiling Characterizes Human Aging via SlipChip-SERS. Advanced Science 2024, 11, 2406668, DOI: 10.1002/advs.202406668Google ScholarThere is no corresponding record for this reference.
- 651Liu, F.; Sun, Z.; Li, B.; Liu, J.; Chen, Z.; Ye, J. Surface-enhanced Raman scattering spatial fingerprinting decodes the digestion behavior of lysosomes in live single cells. VIEW 2024, 5, 20240004, DOI: 10.1002/VIW.20240004Google ScholarThere is no corresponding record for this reference.
- 652He, C.; Liu, F.; Wang, J.; Bi, X.; Pan, J.; Xue, W.; Qian, X.; Chen, Z.; Ye, J. When surface-enhanced Raman spectroscopy meets complex biofluids: A new representation strategy for reliable and comprehensive characterization. Anal. Chim. Acta 2024, 1312, 342767, DOI: 10.1016/j.aca.2024.342767Google ScholarThere is no corresponding record for this reference.
- 653Ye, J.; Bi, X.; Deng, S.; Wang, X.; Liu, Z.; Suo, Q.; Wu, J.; Chen, H.; Wang, Y.; Qian, K.; Shi, R.; Zhao, J.; Yang, G.-Y.; Ye, J.; Tang, Y. Hypoxanthine is a metabolic biomarker for inducing GSDME-dependent pyroptosis of endothelial cells during ischemic stroke. Theranostics 2024, 14, 6071– 6087, DOI: 10.7150/thno.100090Google ScholarThere is no corresponding record for this reference.
- 654Lu, J.; Yuan, K.; Sun, F.; Zheng, K.; Zhang, Z.; Zhu, J.; Wang, X.; Zhang, X.; Zhuang, Y.; Ma, Y.; Cao, X.; Zhang, J.; Tang, D. Self-Assembled Monolayers for the Polymer/Semiconductor Interface with Improved Interfacial Thermal Management. ACS Appl. Mater. & Interfaces 2019, 11, 42708– 42714, DOI: 10.1021/acsami.9b12006Google ScholarThere is no corresponding record for this reference.
- 655Kim, S. Y.; Kang, H.; Chang, K.; Yoon, H. J. Case Studies on Structure-Property Relations in Perovskite Light-Emitting Diodes via Interfacial Engineering with Self-Assembled Monolayers. ACS Appl. Mater. & Interfaces 2021, 13, 31236– 31247, DOI: 10.1021/acsami.1c03797Google ScholarThere is no corresponding record for this reference.
- 656Yuan, X.; Wolf, N.; Hondrich, T. J. J.; Shokoohimehr, P.; Milos, F.; Glass, M.; Mayer, D.; Maybeck, V.; Prömpers, M.; Offenhäusser, A.; Wördenweber, R. Engineering Biocompatible Interfaces via Combinations of Oxide Films and Organic Self-Assembled Monolayers. ACS Appl. Mater. & Interfaces 2020, 12, 17121– 17129, DOI: 10.1021/acsami.0c02141Google ScholarThere is no corresponding record for this reference.
- 657Minamiki, T.; Ichikawa, Y.; Kurita, R. Systematic Investigation of Molecular Recognition Ability in FET-Based Chemical Sensors Functionalized with a Mixed Self-Assembled Monolayer System. ACS Appl. Mater. & Interfaces 2020, 12, 15903– 15910, DOI: 10.1021/acsami.0c00293Google ScholarThere is no corresponding record for this reference.
- 658Tsoutsi, D.; Montenegro, J. M.; Dommershausen, F.; Koert, U.; Liz-Marzán, L. M.; Parak, W. J.; Alvarez-Puebla, R. A. Quantitative Surface-Enhanced Raman Scattering Ultradetection of Atomic Inorganic Ions: The Case of Chloride. ACS Nano 2011, 5, 7539– 7546, DOI: 10.1021/nn2025176Google Scholar658Quantitative Surface-Enhanced Raman Scattering Ultradetection of Atomic Inorganic Ions: The Case of ChlorideTsoutsi, Dionysia; Montenegro, Jose Maria; Dommershausen, Fabian; Koert, Ulrich; Liz-Marzan, Luis M.; Parak, Wolfgang J.; Alvarez-Puebla, Ramon A.ACS Nano (2011), 5 (9), 7539-7546CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Surface-enhanced Raman scattering (SERS) spectroscopy can be used for the detn. and quantification of biol. representative at. ions. The detection and quantification of chloride is demonstrated by monitoring the vibrational changes occurring at a specific interface (a Cl-sensitive dye) supported on a silver-coated silica microbead. The engineered particles play a key role in the detection, as they offer a stable substrate to support the dye, with a dense collection of SERS hot spots. These results open a new avenue toward the generation of microsensors for fast ultradetection and quantification of relevant ions inside living organisms such as cells. Addnl., the use of discrete particles rather than rough films, or other conventional SERS supports, will also enable a safe remote interrogation of highly toxic sources in environmental problems or biol. fluids.
- 659Lee, H. K.; Lee, Y. H.; Koh, C. S. L.; Phan-Quang, G. C.; Han, X.; Lay, C. L.; Sim, H. Y. F.; Kao, Y. C.; An, Q.; Ling, X. Y. Designing surface-enhanced Raman scattering (SERS) platforms beyond hotspot engineering: emerging opportunities in analyte manipulations and hybrid materials. Chem. Soc. Rev. 2019, 48, 731– 756, DOI: 10.1039/C7CS00786HGoogle Scholar659Designing surface-enhanced Raman scattering (SERS) platforms beyond hotspot engineering: emerging opportunities in analyte manipulations and hybrid materialsLee, Hiang Kwee; Lee, Yih Hong; Koh, Charlynn Sher Lin; Phan-Quang, Gia Chuong; Han, Xuemei; Lay, Chee Leng; Sim, Howard Yi Fan; Kao, Ya-Chuan; An, Qi; Ling, Xing YiChemical Society Reviews (2019), 48 (3), 731-756CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)Surface-enhanced Raman scattering (SERS) is a mol.-specific spectroscopic technique with diverse applications in (bio)chem., clin. diagnosis and toxin sensing. While hotspot engineering has expedited SERS development, it is still challenging to detect mols. with no specific affinity to plasmonic surfaces. With the aim of improving detection performances, we venture beyond hotspot engineering in this tutorial review and focus on emerging material design strategies to capture and confine analytes near SERS-active surfaces as well as various promising hybrid SERS platforms. We outline five major approaches to enhance SERS performance: (1) enlarging Raman scattering cross-sections of non-resonant mols. via chem. coupling reactions; (2) targeted chem. capturing of analytes through surface-grafted agents to localize them on plasmonic surfaces; (3) phys. confining liq. analytes on non-wetting SERS-active surfaces and (4) confining gaseous analytes using porous materials over SERS hotspots; (5) synergizing conventional metal-based SERS platforms with functional materials such as graphene, semiconducting materials, and piezoelec. polymers. These approaches can be integrated with engineered hotspots as a multifaceted strategy to further boost SERS sensitivities that are unachievable using hotspot engineering alone. Finally, we highlight current challenges in this research area and suggest new research directions towards efficient SERS designs crit. for real-world applications.
- 660Tan, E. X.; Leong, S. X.; Liew, W. A.; Phang, I. Y.; Ng, J. Y.; Tan, N. S.; Lee, Y. H.; Ling, X. Y. Forward-predictive SERS-based chemical taxonomy for untargeted structural elucidation of epimeric cerebrosides. Nat. Commun. 2024, 15, 2582, DOI: 10.1038/s41467-024-46838-zGoogle ScholarThere is no corresponding record for this reference.
- 661Yang, T.; Ma, J.; Zhen, S. J.; Huang, C. Z. Electrostatic Assemblies of Well-Dispersed AgNPs on the Surface of Electrospun Nanofibers as Highly Active SERS Substrates for Wide-Range pH Sensing. ACS Appl. Mater. & Interfaces 2016, 8, 14802– 14811, DOI: 10.1021/acsami.6b03720Google ScholarThere is no corresponding record for this reference.
- 662Leong, S. X.; Kao, Y. C.; Han, X.; Poh, Z. W.; Chen, J. R. T.; Tan, E. X.; Leong, Y. X.; Lee, Y. H.; Teo, W. X.; Yip, G. W.; Lam, Y.; Ling, X. Y. Achieving Molecular Recognition of Structural Analogues in Surface-Enhanced Raman Spectroscopy: Inducing Charge and Geometry Complementarity to Mimic Molecular Docking. Angew. Chem., Int. Ed. Engl. 2023, 62, e202309610, DOI: 10.1002/anie.202309610Google ScholarThere is no corresponding record for this reference.
- 663Lee, M.; Kim, H.; Kim, E.; Yi, S. Y.; Hwang, S. G.; Yang, S.; Lim, E. K.; Kim, B.; Jung, J.; Kang, T. Multivalent Antibody-Nanoparticle Conjugates To Enhance the Sensitivity of Surface-Enhanced Raman Scattering-Based Immunoassays. ACS Appl. Mater. & Interfaces 2018, 10, 37829– 37834, DOI: 10.1021/acsami.8b13180Google ScholarThere is no corresponding record for this reference.
- 664Wang, C.; Wang, C.; Wang, X.; Wang, K.; Zhu, Y.; Rong, Z.; Wang, W.; Xiao, R.; Wang, S. Magnetic SERS Strip for Sensitive and Simultaneous Detection of Respiratory Viruses. ACS Appl. Mater. & Interfaces 2019, 11, 19495– 19505, DOI: 10.1021/acsami.9b03920Google ScholarThere is no corresponding record for this reference.
- 665Er, E.; Sánchez-Iglesias, A.; Silvestri, A.; Arnaiz, B.; Liz-Marzán, L. M.; Prato, M.; Criado, A. Metal Nanoparticles/MoS2 Surface-Enhanced Raman Scattering-Based Sandwich Immunoassay for α-Fetoprotein Detection. ACS Appl. Mater. & Interfaces 2021, 13, 8823– 8831, DOI: 10.1021/acsami.0c22203Google Scholar665Metal Nanoparticles/MoS2 Surface-Enhanced Raman Scattering-Based Sandwich Immunoassay for α-Fetoprotein DetectionEr, Engin; Sanchez-Iglesias, Ana; Silvestri, Alessandro; Arnaiz, Blanca; Liz-Marzan, Luis M.; Prato, Maurizio; Criado, AlejandroACS Applied Materials & Interfaces (2021), 13 (7), 8823-8831CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)The detection of cancer biomarkers at an early stage of tumor development is vital for effective diagnosis and treatment of cancer. Current diagnostic tools can often detect cancer only when the biomarker levels are already too high, so that the tumors have spread and treatments are less effective. It is urgent therefore to develop highly sensitive assays for the detection of such biomarkers at the lowest possible concn. In this context, we developed a sandwich immunoassay based on surface-enhanced Raman scattering (SERS) for the ultrasensitive detection of α-fetoprotein (AFP), which is typically present in human serum as a biomarker indicative of early stages of hepatocellular carcinoma. In the immunoassay design, molybdenum disulfide (MoS2) modified with a monoclonal antibody was used as a capture probe for AFP. A secondary antibody linked to an SERS-encoded nanoparticle was employed as the Raman signal reporter, i.e., the transducer for AFP detection. The sandwich immunocomplex "capture probe/target/SERS tag" was deposited on a silicon wafer and decorated with silver-coated gold nanocubes to increase the d. of "hot spots" on the surface of the immunosensor. The developed SERS immunosensor exhibits a wide linear detection range (1 pg mL-1 to 10 ng mL-1) with a limit of detection as low as 0.03 pg mL-1 toward AFP with good reproducibility (RSD < 6%) and stability. These parameters demonstrate that the proposed immunosensor has the potential to be used as an anal. platform for the detection of early-stage cancer biomarkers in clin. applications.
- 666Wang, X.; Park, S.-G.; Ko, J.; Xiao, X.; Giannini, V.; Maier, S. A.; Kim, D.-H.; Choo, J. Sensitive and Reproducible Immunoassay of Multiple Mycotoxins Using Surface-Enhanced Raman Scattering Mapping on 3D Plasmonic Nanopillar Arrays. Small 2018, 14, 1801623, DOI: 10.1002/smll.201870179Google ScholarThere is no corresponding record for this reference.
- 667Zhao, Y.; Yang, Y.; Luo, Y.; Yang, X.; Li, M.; Song, Q. Double Detection of Mycotoxins Based on SERS Labels Embedded Ag@Au Core-Shell Nanoparticles. ACS Appl. Mater. & Interfaces 2015, 7, 21780– 21786, DOI: 10.1021/acsami.5b07804Google ScholarThere is no corresponding record for this reference.
- 668Kim, N.; Thomas, M. R.; Bergholt, M. S.; Pence, I. J.; Seong, H.; Charchar, P.; Todorova, N.; Nagelkerke, A.; Belessiotis-Richards, A.; Payne, D. J.; Gelmi, A.; Yarovsky, I.; Stevens, M. M. Surface enhanced Raman scattering artificial nose for high dimensionality fingerprinting. Nat. Commun. 2020, 11, 207, DOI: 10.1038/s41467-019-13615-2Google Scholar668Surface enhanced Raman scattering artificial nose for high dimensionality fingerprintingKim, Nayoung; Thomas, Michael R.; Bergholt, Mads S.; Pence, Isaac J.; Seong, Hyejeong; Charchar, Patrick; Todorova, Nevena; Nagelkerke, Anika; Belessiotis-Richards, Alexis; Payne, David J.; Gelmi, Amy; Yarovsky, Irene; Stevens, Molly M.Nature Communications (2020), 11 (1), 207CODEN: NCAOBW; ISSN:2041-1723. (Nature Research)Label-free surface-enhanced Raman spectroscopy (SERS) can interrogate systems by directly fingerprinting their components' unique physicochem. properties. In complex biol. systems however, this can yield highly overlapping spectra that hinder sample identification. Here, we present an artificial-nose inspired SERS fingerprinting approach where spectral data is obtained as a function of sensor surface chem. functionality. Supported by mol. dynamics modeling, we show that mildly selective self-assembled monolayers can influence the strength and configuration in which analytes interact with plasmonic surfaces, diversifying the resulting SERS fingerprints. Since each sensor generates a modulated signature, the implicit value of increasing the dimensionality of datasets is shown using cell lysates for all possible combinations of up to 9 fingerprints. Reliable improvements in mean discriminatory accuracy towards 100% are achieved with each addnl. surface functionality. This arrayed label-free platform illustrates the wide-ranging potential of high-dimensionality artificial-nose based sensing systems for more reliable assessment of complex biol. matrixes.
- 669Shan, B.; Broza, Y. Y.; Li, W.; Wang, Y.; Wu, S.; Liu, Z.; Wang, J.; Gui, S.; Wang, L.; Zhang, Z.; Liu, W.; Zhou, S.; Jin, W.; Zhang, Q.; Hu, D.; Lin, L.; Zhang, Q.; Li, W.; Wang, J.; Liu, H.; Pan, Y.; Haick, H. Multiplexed Nanomaterial-Based Sensor Array for Detection of COVID-19 in Exhaled Breath. ACS Nano 2020, 14, 12125– 12132, DOI: 10.1021/acsnano.0c05657Google Scholar669Multiplexed Nanomaterial-Based Sensor Array for Detection of COVID-19 in Exhaled BreathShan, Benjie; Broza, Yoav Y.; Li, Wenjuan; Wang, Yong; Wu, Sihan; Liu, Zhengzheng; Wang, Jiong; Gui, Shuyu; Wang, Lin; Zhang, Zhihong; Liu, Wei; Zhou, Shoubing; Jin, Wei; Zhang, Qianyu; Hu, Dandan; Lin, Lin; Zhang, Qiujun; Li, Wenyu; Wang, Jinquan; Liu, Hu; Pan, Yueyin; Haick, HossamACS Nano (2020), 14 (9), 12125-12132CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)This article reports on a noninvasive approach in detecting and following-up individuals who are at-risk or have an existing COVID-19 infection, with a potential ability to serve as an epidemic control tool. The proposed method uses a developed breath device composed of a nanomaterial-based hybrid sensor array with multiplexed detection capabilities that can detect disease-specific biomarkers from exhaled breath, thus enabling rapid and accurate diagnosis. An exploratory clin. study with this approach was examd. in Wuhan, China, during March 2020. The study cohort included 49 confirmed COVID-19 patients, 58 healthy controls, and 33 non-COVID lung infection controls. When applicable, pos. COVID-19 patients were sampled twice: during the active disease and after recovery. Discriminant anal. of the obtained signals from the nanomaterial-based sensors achieved very good test discriminations between the different groups. The training and test set data exhibited resp. 94% and 76% accuracy in differentiating patients from controls as well as 90% and 95% accuracy in differentiating between patients with COVID-19 and patients with other lung infections. While further validation studies are needed, the results may serve as a base for technol. that would lead to a redn. in the no. of unneeded confirmatory tests and lower the burden on hospitals, while allowing individuals a screening soln. that can be performed in PoC facilities. The proposed method can be considered as a platform that could be applied for any other disease infection with proper modifications to the artificial intelligence and would therefore be available to serve as a diagnostic tool in case of a new disease outbreak.
- 670Shang, L.; Liu, C.; Chen, B.; Hayashi, K. Plant Biomarker Recognition by Molecular Imprinting Based Localized Surface Plasmon Resonance Sensor Array: Performance Improvement by Enhanced Hotspot of Au Nanostructure. ACS Sens. 2018, 3, 1531– 1538, DOI: 10.1021/acssensors.8b00329Google Scholar670Plant Biomarker Recognition by Molecular Imprinting Based Localized Surface Plasmon Resonance Sensor Array: Performance Improvement by Enhanced Hotspot of Au NanostructureShang, Liang; Liu, Chuanjun; Chen, Bin; Hayashi, KenshiACS Sensors (2018), 3 (8), 1531-1538CODEN: ASCEFJ; ISSN:2379-3694. (American Chemical Society)Detection of plant volatile org. compds. (VOCs) enables monitoring of pests and diseases in agriculture. The authors previously revealed that a localized surface plasmon resonance (LSPR) sensor coated with a molecularly imprinted sol-gel (MISG) can be used for cis-jasmone vapor detection. Although the selectivity of the LSPR sensor was enhanced by the MISG coating, its sensitivity was decreased. Here, gold nanoparticles (AuNPs) were doped in the MISG to enhance the sensitivity of the LSPR sensor through hot spot generation. The size and amt. of AuNPs added to the MISG were studied and optimized. The sensor coated with the MISG contg. 20 μL of 30 nm AuNPs exhibited higher sensitivity than that of the sensors coated with other films. Furthermore, an optical multichannel sensor platform contg. different channels that were bare and coated with four types of MISGs was developed to detect plant VOCs in single and binary mixts. Linear discriminant anal., k-nearest neighbor (KNN), and naive Bayes classifier approaches were used to establish plant VOC identification models. The KNN model had good potential to identify plant VOCs quickly and efficiently (96.03%). An LSPR sensor array coated with a AuNP-embedded MISG combined with a pattern recognition approach can be used for plant VOC detection and identification. This research is expected to provide useful technologies for agricultural applications.
- 671Geng, Y.; Peveler, W. J.; Rotello, V. M. Array-based ″Chemical Nose″ Sensing in Diagnostics and Drug Discovery. Angew. Chem., Int. Ed. Engl. 2019, 58, 5190– 5200, DOI: 10.1002/anie.201809607Google ScholarThere is no corresponding record for this reference.
- 672Jo, Y.-M.; Jo, Y. K.; Lee, J.-H.; Jang, H. W.; Hwang, I.-S.; Yoo, D. J. MOF-Based Chemiresistive Gas Sensors: Toward New Functionalities. Adv. Mater. 2023, 35, 2206842, DOI: 10.1002/adma.202370308Google ScholarThere is no corresponding record for this reference.
- 673Yuan, H.; Li, N.; Fan, W.; Cai, H.; Zhao, D. Metal-Organic Framework Based Gas Sensors. Advanced Science 2022, 9, e2104374, DOI: 10.1002/advs.202104374Google ScholarThere is no corresponding record for this reference.
- 674Liu, Y.; Chui, K. K.; Fang, Y.; Wen, S.; Zhuo, X.; Wang, J. Metal-Organic Framework-Enabled Trapping of Volatile Organic Compounds into Plasmonic Nanogaps for Surface-Enhanced Raman Scattering Detection. ACS Nano 2024, 18, 11234– 11244, DOI: 10.1021/acsnano.4c00208Google ScholarThere is no corresponding record for this reference.
- 675Qiao, X.; Su, B.; Liu, C.; Song, Q.; Luo, D.; Mo, G.; Wang, T. Selective Surface Enhanced Raman Scattering for Quantitative Detection of Lung Cancer Biomarkers in Superparticle@MOF Structure. Adv. Mater. 2018, 30, 1702275, DOI: 10.1002/adma.201702275Google ScholarThere is no corresponding record for this reference.
- 676Hu, Y.; Liao, J.; Wang, D.; Li, G. Fabrication of gold nanoparticle-embedded metal-organic framework for highly sensitive surface-enhanced Raman scattering detection. Anal. Chem. 2014, 86, 3955– 3963, DOI: 10.1021/ac5002355Google Scholar676Fabrication of Gold Nanoparticle-Embedded Metal-Organic Framework for Highly Sensitive Surface-Enhanced Raman Scattering DetectionHu, Yuling; Liao, Jia; Wang, Dongmei; Li, GongkeAnalytical Chemistry (Washington, DC, United States) (2014), 86 (8), 3955-3963CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Surface-enhanced Raman scattering (SERS) signals strongly rely on the interactions and distance between analyte mols. and metallic nanostructures. The use of a gold nanoparticle (AuNP)-embedded metal-org. framework was introduced for the highly sensitive SERS detection. The AuNPs were in situ grown and encapsulated within the host matrix of MIL-101 by a soln. impregnation strategy. The as-synthesized AuNPs/MIL-101 nanocomposites combined the localized surface plasmon resonance properties of the gold nanoparticles and the high adsorption capability of metal-org. framework, making them highly sensitive SERS substrates by effectively preconcg. analytes in close proximity to the electromagnetic fields at the SERS-active metal surface. The authors discussed the fabrication, phys. characterization, and SERS activity of the authors' novel substrates by measuring the Raman signals of a variety of model analytes. The SERS substrate is highly sensitive, robust, and amiable to several different target analytes. A SERS detection limit of 41.75 and 0.54 fmol for Rhodamine 6G and benzidine, resp., was demonstrated. The substrate also showed high stability and reproducibility, as well as mol. sieving effect thanks to the protective shell of the metal-org. framework. Subsequently, the potential practical application of the novel SERS substrate was evaluated by quant. anal. of org. pollutant p-phenylenediamine in environmental water and tumor marker alpha-fetoprotein in human serum. The method showed good linearity between 1.0 and 100.0 ng/mL for p-phenylenediamine and 1.0-130.0 ng/mL for alpha-fetoprotein with the correlation coeffs. of 0.9950 and -0.9938, resp. The recoveries ranged from 80.5% to 114.7% for p-phenylenediamine in environmental water and 79.3% to 107.3% for alpha-fetoprotein in human serum. These results foresee promising application of the novel metal-org. framework based composites as sensitive SERS-active substrates in both environmental and clin. samples.
- 677Li, Q.; Ge, X.; Ye, J.; Li, Z.; Su, L.; Wu, Y.; Yang, H.; Song, J. Dual Ratiometric SERS and Photoacoustic Core-Satellite Nanoprobe for Quantitatively Visualizing Hydrogen Peroxide in Inflammation and Cancer. Angew. Chem., Int. Ed. Engl. 2021, 60, 7323– 7332, DOI: 10.1002/anie.202015451Google Scholar677Dual Ratiometric SERS and Photoacoustic Core-Satellite Nanoprobe for Quantitatively Visualizing Hydrogen Peroxide in Inflammation and CancerLi Qingqing; Ge Xiaoguang; Ye Jiamin; Li Zhi; Su Lichao; Wu Ying; Yang Huanghao; Song JibinAngewandte Chemie (International ed. in English) (2021), 60 (13), 7323-7332 ISSN:.Excessive production of oxidative species alters the normal redox balance and leads to diseases, such as chronic inflammation and cancer. Oxidative species are short-lived species, which makes direct, precise, and real-time measurements difficult. Herein, we report a novel core-satellite gold nanostructure for dual, ratiometric surface-enhanced Raman scattering (SERS) and photoacoustic (PA) imaging to enable the precise detection of inflammation/cancer-related H2 O2 . The combination of H2 O2 -activated second near-infrared (NIR-II) PA imaging and SERS imaging enables the differentiation between the inflamed region and normal tissue with high accuracy. The mesoporous silica shell of the nanoprobe could be used to deliver drugs to the target area to precisely treat disease. Therefore, this core-satellite nanostructure can not only quantitatively and precisely monitor H2 O2 produced in inflammation, tumor, and osteoarthritis in rabbits in real-time, but can also be used to track the progress of the anti-inflammatory treatment in real-time.
- 678Seydel, C. Single-cell metabolomics hits its stride. Nat. Methods 2021, 18, 1452– 1456, DOI: 10.1038/s41592-021-01333-xGoogle Scholar678Single-cell metabolomics hits its strideSeydel, CarolineNature Methods (2021), 18 (12), 1452-1456CODEN: NMAEA3; ISSN:1548-7091. (Nature Portfolio)An array of new techniques allow researchers to catalog the chem. contents of a single cell, or even a single organelle.
- 679Moragues, T.; Arguijo, D.; Beneyton, T.; Modavi, C.; Simutis, K.; Abate, A. R.; Baret, J.-C.; deMello, A. J.; Densmore, D.; Griffiths, A. D. Droplet-based microfluidics. Nature Reviews Methods Primers 2023, 3, 32, DOI: 10.1038/s43586-023-00212-3Google ScholarThere is no corresponding record for this reference.
- 680Sun, D.; Cao, F. H.; Cong, L. L.; Xu, W. Q.; Chen, Q. D.; Shi, W.; Xu, S. P. Cellular heterogeneity identified by single-cell alkaline phosphatase (ALP) via a SERRS-microfluidic droplet platform. Lab Chip 2019, 19, 335– 342, DOI: 10.1039/C8LC01006DGoogle Scholar680Cellular heterogeneity identified by single-cell alkaline phosphatase (ALP) via a SERRS-microfluidic droplet platformSun, Dan; Cao, Fanghao; Cong, Lili; Xu, Weiqing; Chen, Qidan; Shi, Wei; Xu, ShupingLab on a Chip (2019), 19 (2), 335-342CODEN: LCAHAM; ISSN:1473-0189. (Royal Society of Chemistry)Alk. phosphatase (ALP) is a useful indicator for disease state diagnosis and clin. outcome. Investigation of ALP expression among cells is still challenging since ALP expression in a single cell is too low to be detectable. In our work, an ultrasensitive, high-throughput anal. method was applied for ALP detn. in a single cell by using a surface-enhanced resonance Raman scattering (SERRS)-based microfluidic droplet technique. An ALP catalyzed substrate (5-bromo-4-chloro-3-indolyl phosphate, BCIP) was used to evaluate ALP activity in the cell within one droplet. When BCIP was incubated with cells, ALP can catalyze a hydrolysis reaction of colorless BCIP and oxidize the intermediate compd. to form blue 5,5'-dibromo-4,4'-dichloro-1H,1H-[2,2']biindolylidene-3,3'-dione (BCI), which is a resonant Raman-active species. The encapsulation of BCI in droplets is favorable for detecting extremely low levels of mols. due to an accumulation effect along with reaction time. The ALP concn. as low as 1.0 × 10-15 M can be successfully detected in a uniform droplet. In addn., cellular heterogeneity profiled by ALP expression on single-cell resoln. was monitored with this SERRS-based microfluidic droplet technique. Ultrasensitive detn. of ALP secreted from individual cells can help us to understand cell-to-cell heterogeneity.
- 681Sun, D.; Cao, F. H.; Xu, W. Q.; Chen, Q. D.; Shi, W.; Xu, S. P. Ultrasensitive and Simultaneous Detection of Two Cytokines Secreted by Single Cell in Microfluidic Droplets via Magnetic-Field Amplified SERS. Anal. Chem. 2019, 91, 2551– 2558, DOI: 10.1021/acs.analchem.8b05892Google Scholar681Ultrasensitive and Simultaneous Detection of Two Cytokines Secreted by Single Cell in Microfluidic Droplets via Magnetic-Field Amplified SERSSun, Dan; Cao, Fanghao; Xu, Weiqing; Chen, Qidan; Shi, Wei; Xu, ShupingAnalytical Chemistry (Washington, DC, United States) (2019), 91 (3), 2551-2558CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)A surface-enhanced Raman scattering (SERS)-microfluidic droplet platform for the rapid, ultrasensitive and simultaneous detection of vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) secreted by a single cell is presented. The high-throughput water-in-oil droplets contg. an individual cell along with four kinds of immune-particles (antibody-conjugated silver nanoparticles or magnetic beads, AgNPs@Ab1 and MNs@Ab2) in each were achieved by a cross-typed microfluidic chip, and then they were captured by a collection channel array for SERS measurements. In the appearance of cytokines secreted by one cell, AgNPs@Ab1 can be linked onto the surface of MNs@Ab2 through the immune-recognition to form an immune-sandwich, which makes the "turn on" SERS signal of the Raman reporters previously laid on the surface of MNs due to the adjacent AgNPs. Furthermore, the second SERS signal amplification is from the magnetic field-induced spontaneous collection effect, which brings 75 times enhancement for SERS signal. Addnl., the encapsulation of cytokines in an isolated droplet permits an accumulation effect of targets with time. Owing to the dual signal enhancement and the accumulation effect, such few cytokines secreted by a single cell become detectable and a limit of detection is achieved as 1.0 fg/mL in one droplet. By using this ultrasensitive SERS-microdroplet method, the VEGF and IL-8 secretions from several cells in one droplet were explored and the data show that the cell-cell interaction may promote angiogenesis of cancer cells through the up-regulation of VEGF and IL-8.
- 682Cong, L. L.; Wang, J. Q.; Li, X. L.; Tian, Y.; Xu, S. Z.; Liang, C. Y.; Xu, W. Q.; Wang, W. G.; Xu, S. P. Microfluidic Droplet-SERS Platform for Single-Cell Cytokine Analysis via a Cell Surface Bioconjugation Strategy. Anal. Chem. 2022, 94, 10375– 10383, DOI: 10.1021/acs.analchem.2c01249Google Scholar682Microfluidic Droplet-SERS Platform for Single-Cell Cytokine Analysis via a Cell Surface Bioconjugation StrategyCong, Lili; Wang, Jiaqi; Li, Xinli; Tian, Yu; Xu, Shizhi; Liang, Chongyang; Xu, Weiqing; Wang, Weigang; Xu, ShupingAnalytical Chemistry (Washington, DC, United States) (2022), 94 (29), 10375-10383CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)A microfluidic-based surface-enhanced Raman scattering (SERS) platform for analyzing cytokines secreted by single cells is reported based on the elaborate bioconjugation of the immuno-sandwich complex on the probed cell surface. This platform integrates the dual functions of microfluidic droplet sepn. of single cells and SERS measurement. Two immune nanoprobes (capture probe and SERS probe) are introduced into a microfluidic droplet along with a single cell. They were anchored to the cell membrane protein surface by capturing secreted cytokines to form an immune sandwich structure, realizing the enrichment effect of cytokines above the cell membrane surface and the amplification effect of SERS detection probes. This single-cell anal. platform was applied to track specific cell-secreted vascular endothelial growth factor (VEGF) of different cell lines (MCF-7, SGC, and T24), and highly sensitive detection of VEGF was achieved. Chemometric methods (principal component anal. and t-distributed stochastic neighbor embedding) were adopted for the SERS data anal., and the support vector machine (SVM) discriminant model was established to test the data. These chemometric methods successfully identify significant differences in the secreting ability of cytokines among three kinds of cancer cell lines, revealing cell heterogeneity. In addn., the behavior of single cells secreting VEGF was monitored time-dependently and was shown to increase with time. This work demonstrates the importance of tracking specific cells secreting cytokines based on the cell surface bioconjugation strategy. Our developed platform provides guidelines for using the single-cell exocytosis factors as biomarkers to assess the early diagnosis of cancer and provide physiol. cues for learning single-cell secretions.
- 683Wang, J. Q.; Cong, L. L.; Shi, W.; Xu, W. Q.; Xu, S. P. Single-Cell Analysis and Classification according to Multiplexed Proteins via Microdroplet-Based Self-Driven Magnetic Surface-Enhanced Raman Spectroscopy Platforms Assisted with Machine Learning Algorithms. Anal. Chem. 2023, 95, 11019– 11027, DOI: 10.1021/acs.analchem.3c01273Google ScholarThere is no corresponding record for this reference.
- 684Wang, X.; Wang, J. Q.; Xu, S. P. Microdroplet-SERS platform for single cell-secreted VEGF and extracellular pH analysis in oxidative stress event. Sensors and Actuators: B. Chemical 2025, 422, 136545, DOI: 10.1016/j.snb.2024.136545Google ScholarThere is no corresponding record for this reference.
- 685Sun, D.; Cao, F. H.; Tian, Y.; Li, A. S.; Xu, W. Q.; Chen, Q. D.; Shi, W.; Xu, S. P. Label-Free Detection of Multiplexed Metabolites at Single-Cell Level via a SERS-Microfluidic Droplet Platform. Anal. Chem. 2019, 91, 15484– 15490, DOI: 10.1021/acs.analchem.9b03294Google Scholar685Label-Free Detection of Multiplexed Metabolites at Single-Cell Level via a SERS-Microfluidic Droplet PlatformSun, Dan; Cao, Fanghao; Tian, Yu; Li, Aisen; Xu, Weiqing; Chen, Qidan; Shi, Wei; Xu, ShupingAnalytical Chemistry (Washington, DC, United States) (2019), 91 (24), 15484-15490CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Single-cell metabolomics could be used to discover the chem. strategies of cells for coping with chem. or environmental stress because metabolomics provides a more immediate and dynamic picture of cell functionality. However, these small-mol. metabolites are the most difficult to measure because they characterize rapid metabolic dynamics, structural diversity, and incapacity to achieve signal amplification or labeling. In order to solve above problems, we presented a surface-enhanced Raman scattering (SERS)-microfluidic droplet platform to realize the label-free simultaneous anal. of multiplexed metabolites at the single-cell level via a versatile magnetic SERS substrate composed by silver nanoparticles (AgNPs, 30 nm)-decorated 400 nm Fe3O4 magnetic microspheres. This metal-magnetic composite substrate is beneficial to efficient adsorption of single cell metabolites, fast sepn. from complex matrixes, and high SERS sensitivity. Also, the endocytosis effect can be fully prohibited due to its relatively large size. This work achieves label-free, nondestructive, simultaneous detn. of three single-cell metabolites, pyruvate, ATP (ATP), and lactate, owing to their intrinsic SERS fingerprints. The "hotspots" effect induced by the magnetic aggregation of Fe3O4@AgNPs allows highly sensitive SERS detection. Encapsulating metabolites in such a limited and isolated droplet accelerates the process of diffusion and adsorption equil. Activation with saponin for metabolites was assessed on different cell lines. The SERS-microdroplet platform is a powerful tool for exploring single-cell heterogeneity at the metabolic level.
- 686Sun, D.; Cao, F. H.; Yi, X.; Zhu, H. Y.; Qi, G. H.; Xu, W. Q.; Xu, S. P. MicroRNA-21 expression in single living cells revealed by fluorescence and SERS dual-response microfluidic droplet platform. Lab Chip 2022, 22, 2165– 2172, DOI: 10.1039/D2LC00096BGoogle Scholar686MicroRNA-21 expression in single living cells revealed by fluorescence and SERS dual-response microfluidic droplet platformSun, Dan; Cao, Fanghao; Yi, Xuan; Zhu, Hongyan; Qi, Guohua; Xu, Weiqing; Xu, ShupingLab on a Chip (2022), 22 (11), 2165-2172CODEN: LCAHAM; ISSN:1473-0189. (Royal Society of Chemistry)Anal. of single-cell microRNA is essential to reveal cell heterogeneity at the genetic level. It raises a high demand for single-cell anal. methods because single-cell microRNA sequences are highly similar and small in size and feature low-level expression. Herein, SERS and fluorescence imaging technol. were introduced into a microfluidic droplet platform to realize direct in situ, nondestructive, and highly sensitive detection of a small no. of microRNA-21 (miR-21) in a single intact living cell. A multifunctional plasmonic nanoprobe was designed by decorating a gold nanoparticle with fluorescent dye (ROX)-labeled probe DNA and capture DNA strands. The dual-signal switching of fluorescence turn-off and SERS turn-on of ROX in response to miR-21 achieves highly sensitive and reliable detection of miR-21 in a single cell. The turn-on of SERS signal with a zero background guarantees the sensitivity of the detection. The fluorescence-SERS simultaneous response strategy was able to mutually corroborate the test results, improving the reliability of detg. low-level expression of miR-21. SERS combined with encapsulation of microdroplets provides a feasible way to conduct in situ, nondestructive detn. of miR-21 secreted by single cells, avoiding cell lysis and tedious time-consuming steps of miR-21 isolation. As a result, the miR-21 expressed by various types of single cells was investigated by fluorescence imaging and the cellular heterogeneity in miR-21 expression was evaluated accurately and quant. by SERS. This research would provide important ref. information for understanding the effects of miRNAs on cancer diseases at the single-cell level.
- 687Kalluri, R.; McAndrews, K. M. The role of extracellular vesicles in cancer. Cell 2023, 186, 1610– 1626, DOI: 10.1016/j.cell.2023.03.010Google Scholar687The role of extracellular vesicles in cancerKalluri, Raghu; McAndrews, Kathleen M.Cell (Cambridge, MA, United States) (2023), 186 (8), 1610-1626CODEN: CELLB5; ISSN:0092-8674. (Cell Press)A review. Intercellular communication is a key feature of cancer progression and metastasis. Extracellular vesicles (EVs) are generated by all cells, including cancer cells, and recent studies have identified EVs as key mediators of cell-cell communication via packaging and transfer of bioactive constituents to impact the biol. and function of cancer cells and cells of the tumor microenvironment. Here, we review recent advances in understanding the functional contribution of EVs to cancer progression and metastasis, as cancer biomarkers, and the development of cancer therapeutics.
- 688Alix-Panabières, C.; Pantel, K. Liquid Biopsy: From Discovery to Clinical Application. Cancer Discov 2021, 11, 858– 873, DOI: 10.1158/2159-8290.CD-20-1311Google ScholarThere is no corresponding record for this reference.
- 689De Giorgis, V.; Barberis, E.; Manfredi, M. Extracellular vesicles proteins for early cancer diagnosis: From omics to biomarkers. Semin Cancer Biol. 2024, 104–105, 18– 31, DOI: 10.1016/j.semcancer.2024.07.003Google ScholarThere is no corresponding record for this reference.
- 690Han, J.; Jung, J. H.; Lee, S. Y.; Park, J. H. Nanoplasmonic Detection of EGFR Mutations Based on Extracellular Vesicle-Derived EGFR-Drug Interaction. ACS Appl. Mater. Interfaces 2024, 16, 8266– 8274, DOI: 10.1021/acsami.3c14907Google ScholarThere is no corresponding record for this reference.
- 691Hinestrosa, J. P.; Kurzrock, R.; Lewis, J. M. Early-stage multi-cancer detection using an extracellular vesicle protein-based blood test. Commun Med 2022, 2, 29, DOI: 10.1038/s43856-022-00088-6Google Scholar691Early-stage multi-cancer detection using an extracellular vesicle protein-based blood testHinestrosa, Juan Pablo; Kurzrock, Razelle; Lewis, Jean M.; Schork, Nicholas J.; Schroeder, Gregor; Kamat, Ashish M.; Lowy, Andrew M.; Eskander, Ramez N.; Perrera, Orlando; Searson, David; Rastegar, Kiarash; Hughes, Jake R.; Ortiz, Victor; Clark, Iryna; Balcer, Heath I.; Arakelyan, Larry; Turner, Robert; Billings, Paul R.; Adler, Mark J.; Lippman, Scott M.; Krishnan, RajaramCommunications Medicine (2022), 2 (1), 29CODEN: CMOECM; ISSN:2730-664X. (Nature Portfolio)Abstr.: Background: Detecting cancer at early stages significantly increases patient survival rates. Because lethal solid tumors often produce few symptoms before progressing to advanced, metastatic disease, diagnosis frequently occurs when surgical resection is no longer curative. One promising approach to detect early-stage, curable cancers uses biomarkers present in circulating extracellular vesicles (EVs). To explore the feasibility of this approach, we developed an EV-based blood biomarker classifier from EV protein profiles to detect stages I and II pancreatic, ovarian, and bladder cancer. Methods: Utilizing an a.c. electrokinetics (ACE) platform to purify EVs from plasma, we use multi-marker EV-protein measurements to develop a machine learning algorithm that can discriminate cancer cases from controls. The ACE isolation method requires small sample vols., and the streamlined process permits integration into high-throughput workflows. Results: In this case-control pilot study, comparison of 139 pathol. confirmed stage I and II cancer cases representing pancreatic, ovarian, or bladder patients against 184 control subjects yields an area under the curve (AUC) of 0.95 (95% CI: 0.92 to 0.97), with sensitivity of 71.2% (95% CI: 63.2 to 78.1) at 99.5% (97.0 to 99.9) specificity. Sensitivity is similar at both early stages [stage I: 70.5% (60.2 to 79.0) and stage II: 72.5% (59.1 to 82.9)]. Detection of stage I cancer reaches 95.5% in pancreatic, 74.4% in ovarian (73.1% in Stage IA) and 43.8% in bladder cancer. Conclusions: This work demonstrates that an EV-based, multi-cancer test has potential clin. value for early cancer detection and warrants future expanded studies involving prospective cohorts with multi-year follow-up.
- 692Tavakkoli Yaraki, M.; Tukova, A.; Wang, Y. Emerging SERS biosensors for the analysis of cells and extracellular vesicles. Nanoscale 2022, 14, 15242– 15268, DOI: 10.1039/D2NR03005EGoogle ScholarThere is no corresponding record for this reference.
- 693Lee, C.; Carney, R. P.; Hazari, S.; Smith, Z. J.; Knudson, A.; Robertson, C. S.; Lam, K. S.; Wachsmann-Hogiu, S. 3D plasmonic nanobowl platform for the study of exosomes in solution. Nanoscale 2015, 7, 9290– 7, DOI: 10.1039/C5NR01333JGoogle Scholar6933D plasmonic nanobowl platform for the study of exosomes in solutionLee, Changwon; Carney, Randy P.; Hazari, Sidhartha; Smith, Zachary J.; Knudson, Alisha; Robertson, Christopher S.; Lam, Kit S.; Wachsmann-Hogiu, SebastianNanoscale (2015), 7 (20), 9290-9297CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)Thin silver film coated nanobowl Surface Enhanced Raman Spectroscopy (SERS) substrates are used to capture exosomes in soln. for SERS measurements that can provide biochem. anal. of intact and ruptured exosomes. Exosomes derived via Total Exosome Isolation Reagent (TEIR) as well as ultracentrifugation (UC) from the SKOV3 cell line were analyzed. Spectra of exosomes derived via TEIR are dominated by a signal characteristic for the TEIR kit that needs to be subtracted for all measurements. Differences in SERS spectra recorded at different times during the drying of the exosome soln. are statistically analyzed with Principal Component Anal. (PCA). At the beginning of the drying process, SERS spectra of exosomes exhibit peaks characteristic for both lipids and proteins. Later on during the drying process, new SERS peaks develop, suggesting that the initially intact exosome ruptures over time. This time-dependent evolution of SERS peaks enables anal. of exosomal membrane contents and the contents inside the exosomes.
- 694Fraire, J. C.; Stremersch, S.; Bouckaert, D.; Monteyne, T.; De Beer, T.; Wuytens, P.; De Rycke, R.; Skirtach, A. G.; Raemdonck, K.; De Smedt, S.; Braeckmans, K. Improved Label-Free Identification of Individual Exosome-like Vesicles with Au@Ag Nanoparticles as SERS Substrate. ACS Appl. Mater. Interfaces 2019, 11, 39424– 39435, DOI: 10.1021/acsami.9b11473Google Scholar694Improved Label-Free Identification of Individual Exosome-like Vesicles with Au@Ag Nanoparticles as SERS SubstrateFraire, Juan C.; Stremersch, Stephan; Bouckaert, Davinia; Monteyne, Tinne; De Beer, Thomas; Wuytens, Pieter; De Rycke, Riet; Skirtach, Andre G.; Raemdonck, Koen; De Smedt, Stefaan; Braeckmans, KevinACS Applied Materials & Interfaces (2019), 11 (43), 39424-39435CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Exosome-like vesicles (ELVs) are nanovectors released by cells which are endowed with a variety of mols., including proteins, nucleic acids and chems. that reflect the mol. signature of the producing cell. Given their presence in many biofluids they form an easily accessible biomarker for early disease detection. Previously the authors demonstrated the possibility of identifying individual ELVs by analyzing their mol. signatures with Surface Enhanced Raman Scattering (SERS) after functionalization of ELVs with 4-Dimethylaminopyridine (DMAP)-stabilized gold nanoparticles (AuNP). Although this strategy was capable of distinguishing ELVs from different cellular origins, the quality of the SERS spectra was suboptimal due to high background coming from the DMAP stabilizing mols. at the AuNP surface. In this study the authors demonstrate that it is possible to eliminate interfering SERS signals from stabilizing mols. at the AuNP surface by overgrowing in situ the ELV-attached AuNP with a silver layer so as to form a core-shell nanoparticle (Au@AgNPs) directly at the ELV surface. As such it represents the first known strategy to generate clear SERS spectral fingerprints of delicate biol. structures without interference of linker mols. that are needed to ensure colloidal stability of the plasmonic NP and to allow them to assoc. to the ELV surface. This new strategy using core-shell plasmonic NPs as SERS substrate showed higher near-field enhancements than previous approaches, which resulted in SERS spectra with improved signal to noise ratio. This allowed us to discriminate individual vesicles derived from B16F10 melanoma cells and red blood cells (RBC) with an unprecedented sensitivity and specificity > 90%. Importantly, thanks to the higher near field enhancement the acquisition time could be reduced by 20-fold in comparison to previously reported strategies, paving the way towards high-throughput label-free single ELV identification.
- 695Koster, H. J.; Rojalin, T.; Powell, A.; Pham, D.; Mizenko, R. R.; Birkeland, A. C.; Carney, R. P. Surface enhanced Raman scattering of extracellular vesicles for cancer diagnostics despite isolation dependent lipoprotein contamination. Nanoscale 2021, 13, 14760– 14776, DOI: 10.1039/D1NR03334DGoogle Scholar695Surface enhanced Raman scattering of extracellular vesicles for cancer diagnostics despite isolation dependent lipoprotein contaminationKoster, Hanna J.; Rojalin, Tatu; Powell, Alyssa; Pham, Dina; Mizenko, Rachel R.; Birkeland, Andrew C.; Carney, Randy P.Nanoscale (2021), 13 (35), 14760-14776CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)Given the emerging diagnostic utility of extracellular vesicles (EVs), it is important to account for non-EV contaminants. Lipoprotein present in EV-enriched isolates may inflate particle counts and decrease sensitivity to biomarkers of interest, skewing chem. analyses and perpetuating downstream issues in labeling or functional anal. Using label free surface enhanced Raman scattering (SERS), we confirm that three common EV isolation methods (differential ultracentrifugation, d. gradient ultracentrifugation, and size exclusion chromatog.) yield variable lipoprotein content. We demonstrate that a dual-isolation method is necessary to isolate EVs from the major classes of lipoprotein. However, combining SERS anal. with machine learning assisted classification, we show that the disease state is the main driver of distinction between EV samples, and largely unaffected by choice of isolation. Ultimately, this study describes a convenient SERS assay to retain accurate diagnostic information from clin. samples by overcoming differences in lipoprotein contamination according to isolation method.
- 696Beeram, R.; Vepa, K. R.; Soma, V. R. Recent Trends in SERS-Based Plasmonic Sensors for Disease Diagnostics, Biomolecules Detection, and Machine Learning Techniques. Biosensors (Basel) 2023, 13, 328, DOI: 10.3390/bios13030328Google ScholarThere is no corresponding record for this reference.
- 697Rojalin, T.; Koster, H. J.; Liu, J.; Mizenko, R. R.; Tran, D.; Wachsmann-Hogiu, S.; Carney, R. P. Hybrid Nanoplasmonic Porous Biomaterial Scaffold for Liquid Biopsy Diagnostics Using Extracellular Vesicles. ACS Sens 2020, 5, 2820– 2833, DOI: 10.1021/acssensors.0c00953Google Scholar697Hybrid Nanoplasmonic Porous Biomaterial Scaffold for Liquid Biopsy Diagnostics Using Extracellular VesiclesRojalin, Tatu; Koster, Hanna J.; Liu, Juanjuan; Mizenko, Rachel R.; Tran, Di; Wachsmann-Hogiu, Sebastian; Carney, Randy P.ACS Sensors (2020), 5 (9), 2820-2833CODEN: ASCEFJ; ISSN:2379-3694. (American Chemical Society)For more effective early-stage cancer diagnostics, there is a need to develop sensitive and specific, non- or minimally invasive, and cost-effective methods for identifying circulating nanoscale extracellular vesicles (EVs). Here, we report the utilization of a simple plasmonic scaffold composed of a microscale biosilicate substrate embedded with silver nanoparticles for surface-enhanced Raman scattering (SERS) anal. of ovarian and endometrial cancer EVs. These substrates are rapidly and inexpensively produced without any complex equipment or lithog. We extensively characterize the substrates with electron microscopy and outline a reproducible methodol. for their use in analyzing EVs from in vitro and in vivo biofluids. We report effective chem. treatments for (i) decoration of metal surfaces with cysteamine to nonspecifically pull down EVs to SERS hotspots and (ii) enzymic cleavage of extraluminal moieties at the surface of EVs that prevent localization of complementary chem. features (lipids/proteins) to the vicinity of the metal-enhanced fields. We observe a major loss of sensitivity for ovarian and endometrial cancer following enzymic cleavage of EVs' extraluminal domain, suggesting its crit. significance for diagnostic platforms. We demonstrate that the SERS technique represents an ideal tool to assess and measure the high heterogeneity of EVs isolated from clin. samples in an inexpensive, rapid, and label-free assay.
- 698Jalali, M.; Isaac Hosseini, I.; AbdelFatah, T.; Montermini, L.; Wachsmann Hogiu, S.; Rak, J.; Mahshid, S. Plasmonic nanobowtiefluidic device for sensitive detection of glioma extracellular vesicles by Raman spectrometry. Lab Chip 2021, 21, 855– 866, DOI: 10.1039/D0LC00957AGoogle Scholar698Plasmonic nanobowtiefluidic device for sensitive detection of glioma extracellular vesicles by Raman spectrometryJalali, Mahsa; Isaac Hosseini, Imman; AbdelFatah, Tamer; Montermini, Laura; Wachsmann Hogiu, Sebastian; Rak, Janusz; Mahshid, SaraLab on a Chip (2021), 21 (5), 855-866CODEN: LCAHAM; ISSN:1473-0189. (Royal Society of Chemistry)Cancer cells shed into biofluids extracellular vesicles (EVs) - nanoscale membrane particles carrying diagnostic information. EVs shed by heterogeneous populations of tumor cells offer a unique opportunity to access biol. important aspects of disease complexity. Glioblastoma (GBM) exemplifies cancers that are incurable, because their temporal dynamics and mol. complexity evade std. diagnostic methods and confound therapeutic efforts. Liq. biopsy based on EVs offers unprecedented real-time access to complex tumor signatures, but it is not used clin. due to inefficient testing methods. We report on a nanostructured microfluidic-device that employs SERS for unambiguous identification of EVs from different GBM cell populations. The device features fabless plasmonic nanobowties for label-free and non-immunol. SERS detection of EVs. This nanobowtiefluidic device combines the advanced characteristics of plasmonic nanobowties with a high throughput sample-delivery system for concn. of the analytes in the vicinity of the detection site. We showed theor. and exptl. that the fluidic device assists the monolayer distribution of the EVs, which dramatically increase the probability of EV's existence in the laser illumination area. In addn., the optimized fabless nanobowtie structures with an av. elec. field enhancement factor of 9 x 105 achieve distinguishable and high intensity SERS signals.
- 699Tavakkoli Yaraki, M.; Wongtrakul-Kish, K.; Moh, E. S. X.; Packer, N. H.; Wang, Y. Lectin-conjugated nanotags with high SERS stability: selective probes for glycans. Analyst 2024, 149, 1774– 1783, DOI: 10.1039/D3AN02108DGoogle ScholarThere is no corresponding record for this reference.
- 700Li, Y.; Zhang, S.; Liu, C. Thermophoretic glycan profiling of extracellular vesicles for triple-negative breast cancer management. Nat Commun 2024, 15, 2292, DOI: 10.1038/s41467-024-46557-5Google ScholarThere is no corresponding record for this reference.
- 701Zhou, Q.; Niu, X.; Zhang, Z.; O’Byrne, K.; Kulasinghe, A.; Fielding, D.; Möller, A.; Wuethrich, A.; Lobb, R. J.; Trau, M. Glycan Profiling in Small Extracellular Vesicles with a SERS Microfluidic Biosensor Identifies Early Malignant Development in Lung Cancer. Advanced Science 2024, 11, 2401818, DOI: 10.1002/advs.202401818Google ScholarThere is no corresponding record for this reference.
- 702Kazemzadeh, M.; Martinez-Calderon, M.; Otupiri, R.; Artuyants, A.; Lowe, M.; Ning, X.; Reategui, E.; Schultz, Z. D.; Xu, W.; Blenkiron, C.; Chamley, L. W.; Broderick, N. G. R.; Hisey, C. L. Deep autoencoder as an interpretable tool for Raman spectroscopy investigation of chemical and extracellular vesicle mixtures. Biomed Opt Express 2024, 15, 4220– 4236, DOI: 10.1364/BOE.522376Google ScholarThere is no corresponding record for this reference.
- 703Welsh, J. A.; Goberdhan, D. C. I.; O’Driscoll, L.; Buzas, E. I.; Blenkiron, C.; Bussolati, B.; Cai, H.; Di Vizio, D.; Driedonks, T. A. P.; Erdbrügger, U.; Falcon-Perez, J. M.; Fu, Q. L.; Hill, A. F.; Lenassi, M.; Lim, S. K.; Mahoney, M. G.; Mohanty, S.; Möller, A.; Nieuwland, R.; Ochiya, T.; Sahoo, S.; Torrecilhas, A. C.; Zheng, L.; Zijlstra, A.; Abuelreich, S.; Bagabas, R.; Bergese, P.; Bridges, E. M.; Brucale, M.; Burger, D.; Carney, R. P.; Cocucci, E.; Crescitelli, R.; Hanser, E.; Harris, A. L.; Haughey, N. J.; Hendrix, A.; Ivanov, A. R.; Jovanovic-Talisman, T.; Kruh-Garcia, N. A.; Ku’ulei-Lyn Faustino, V.; Kyburz, D.; Lässer, C.; Lennon, K. M.; Lötvall, J.; Maddox, A. L.; Martens-Uzunova, E. S.; Mizenko, R. R.; Newman, L. A.; Ridolfi, A.; Rohde, E.; Rojalin, T.; Rowland, A.; Saftics, A.; Sandau, U. S.; Saugstad, J. A.; Shekari, F.; Swift, S.; Ter-Ovanesyan, D.; Tosar, J. P.; Useckaite, Z.; Valle, F.; Varga, Z.; van der Pol, E.; van Herwijnen, M. J. C.; Wauben, M. H. M.; Wehman, A. M.; Williams, S.; Zendrini, A.; Zimmerman, A. J.; Théry, C.; Witwer, K. W. Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches. J. Extracell Vesicles 2024, 13, e12404, DOI: 10.1002/jev2.12404Google ScholarThere is no corresponding record for this reference.
- 704Markus, A. F.; Kors, J. A.; Rijnbeek, P. R. The role of explainability in creating trustworthy artificial intelligence for health care: A comprehensive survey of the terminology, design choices, and evaluation strategies. J. Biomed Inform 2021, 113, 103655, DOI: 10.1016/j.jbi.2020.103655Google ScholarThere is no corresponding record for this reference.
- 705Wang, J.; Trau, M.; Wuethrich, A. A Microfluidic SERS Assay to Characterize the Phenotypic Heterogeneity in Cancer-Derived Small Extracellular Vesicles. Methods Mol. Biol. 2023, 2679, 241– 253, DOI: 10.1007/978-1-0716-3271-0_17Google ScholarThere is no corresponding record for this reference.
- 706Veliz, L.; Cooper, T. T.; Grenier-Pleau, I.; Abraham, S. A.; Gomes, J.; Pasternak, S. H.; Dauber, B.; Postovit, L. M.; Lajoie, G. A.; Lagugné-Labarthet, F. Tandem SERS and MS/MS Profiling of Plasma Extracellular Vesicles for Early Ovarian Cancer Biomarker Discovery. ACS Sens 2024, 9, 272– 282, DOI: 10.1021/acssensors.3c01908Google ScholarThere is no corresponding record for this reference.
- 707Sloan-Dennison, S.; Wallace, G. Q.; Hassanain, W. A. Advancing SERS as a quantitative technique: challenges, considerations, and correlative approaches to aid validation. Nano Convergence 2024, 11, 33, DOI: 10.1186/s40580-024-00443-4Google ScholarThere is no corresponding record for this reference.
- 708Jiang, C.; Wang, Y.; Song, W.; Lu, L. Delineating the tumor margin with intraoperative surface-enhanced Raman spectroscopy. Anal. Bioanal. Chem. 2019, 411, 3993– 4006, DOI: 10.1007/s00216-019-01577-9Google Scholar708Delineating the tumor margin with intraoperative surface-enhanced Raman spectroscopyJiang, Chunhuan; Wang, Ying; Song, Wei; Lu, LehuiAnalytical and Bioanalytical Chemistry (2019), 411 (18), 3993-4006CODEN: ABCNBP; ISSN:1618-2642. (Springer)A review. The failure of complete tumor resection during cancer surgery is a leading cause of lethal recurrence and metastasis. However, achieving accurate delineation of tumor margins intraoperatively remains extremely difficult because the infiltrated nature of a tumor usually gives an obscure margin and spreading microtumors. Recent studies show that surface-enhanced Raman scattering (SERS) has the potential to depict precisely the actual tumor extent with high sensitivity, specificity, and spatial resoln.; thus providing a promising platform to improve the therapeutic efficiency. In this review, the recent progress in the use of SERS spectroscopy for intraoperative image-guided resection are discussed. The authors highlight key successes in the development of SERS tags and give insights into the design mechanism of rational SERS tags. The authors also discuss how to improve the performance of intraoperative navigation based on SERS and explore the challenges and future opportunities for the development of a more effective SERS-based platform.
- 709Deng, S.; Gu, J.; Jiang, Z.; Cao, Y.; Mao, F.; Xue, Y.; Wang, J.; Dai, K.; Qin, L.; Liu, K.; Wu, K.; He, Q.; Cai, K. Application of nanotechnology in the early diagnosis and comprehensive treatment of gastrointestinal cancer. J. Nanobiotechnol. 2022, 20, 415, DOI: 10.1186/s12951-022-01613-4Google ScholarThere is no corresponding record for this reference.
- 710Hu, S.; Brooks, D.; Nemirovsky, D.; Gupta, P.; Chiu, B.; Razavi, M. Detecting esophageal cancer using surface-enhanced Raman spectroscopy: a narrative review. Annals of Esophagus 2024, 7, 4, DOI: 10.21037/aoe-22-24Google ScholarThere is no corresponding record for this reference.
- 711Davis, R. M.; Kiss, B.; Trivedi, D. R.; Metzner, T. J.; Liao, J. C.; Gambhir, S. S. Surface-Enhanced Raman Scattering Nanoparticles for Multiplexed Imaging of Bladder Cancer Tissue Permeability and Molecular Phenotype. ACS Nano 2018, 12, 9669– 9679, DOI: 10.1021/acsnano.8b03217Google Scholar711Surface-Enhanced Raman Scattering Nanoparticles for Multiplexed Imaging of Bladder Cancer Tissue Permeability and Molecular PhenotypeDavis, Ryan M.; Kiss, Bernhard; Trivedi, Dharati R.; Metzner, Thomas J.; Liao, Joseph C.; Gambhir, Sanjiv S.ACS Nano (2018), 12 (10), 9669-9679CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Bladder cancer has the highest recurrence rate of all cancers due in part to inadequate transurethral resection. Inadequate resection is caused by the inability of cystoscopes to detect invisible lesions during the resection procedure. To improve detection and resection of nonmuscle invasive bladder cancer, the authors quantified the ability of a surface-enhanced Raman nanoparticle and endoscope system to classify bladder tissue as normal or cancerous. Both antibody-based (active) and tissue permeability-based (passive) targeting mechanisms were evaluated by topically applying nanoparticles to ex vivo human bladder tissue samples. Multiplexed mol. imaging of CD47 and Carbonic Anhydrase 9 tumor proteins gave a receiver operating characteristic area under the curve (ROC AUC of 0.93, 0.75, 1.00). Furthermore, passively targeted nanoparticles enabled tissue classification with an ROC AUC of 0.93 (0.73, 1.00). Passively targeted nanoparticles penetrated 5-fold deeper and bound to tumor tissue at 3.3-fold higher concns. in cancer compared to normal bladder urothelium, suggesting the existence of an enhanced surface permeability and retention effect in human bladder cancer.
- 712Wu, Z.; Wang, Z.; Xie, H.; Wang, Y.; He, H.; Nie, S.; Ye, J.; Lin, L. Raman-Guided Bronchoscopy: Feasibility and Detection Depth Studies Using Ex Vivo Lung Tissues and SERS Nanoparticle Tags. Photonics 2022, 9, 429, DOI: 10.3390/photonics9060429Google ScholarThere is no corresponding record for this reference.
- 713Zhang, Q.; Inose, T.; Ricci, M.; Li, J.; Tian, Y.; Wen, H.; Toyouchi, S.; Fron, E.; Ngoc Dao, A. T.; Kasai, H.; Rocha, S.; Hirai, K.; Fortuni, B.; Uji-i, H. Gold-Photodeposited Silver Nanowire Endoscopy for Cytosolic and Nuclear pH Sensing. ACS Applied Nano Materials 2021, 4, 9886– 9894, DOI: 10.1021/acsanm.1c02363Google ScholarThere is no corresponding record for this reference.
- 714Li, P.; Pan, D.; Yang, L.; Wei, H.; He, S.; Xu, H.; Li, Z. Silver nano-needles: focused optical field induced solution synthesis and application in remote-excitation nanofocusing SERS. Nanoscale 2019, 11, 2153– 2161, DOI: 10.1039/C8NR07141AGoogle Scholar714Silver nano-needles: focused optical field induced solution synthesis and application in remote-excitation nanofocusing SERSLi, Pan; Pan, Deng; Yang, Longkun; Wei, Hong; He, Shuli; Xu, Hongxing; Li, ZhipengNanoscale (2019), 11 (5), 2153-2161CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)Tapered metallic nanostructures that harbor surface plasmons are highly interesting for nanophotonic applications because of their waveguiding and field-focusing properties. Here, we developed a focused optical field induced soln. synthesis for unique crystd. silver nano-needles. Under the focused laser spot, inhomogeneous Ag monomer concn. is created, which triggers the uniaxial growth of silver nanostructures along the radial direction with decreasing rate, forming nano-needle structures. These nano-needles are several micrometers long, with diam. attenuating from hundreds to tens of nanometers, and terminated by a sharp apex only a few nanometers in diam. Moreover, nano-needles with atomically smooth surfaces show excellent performance for plasmonic waveguiding and unique near-field compression abilities. This nano-needle structure can be used for effective remote-excitation detection/sensing. We also demonstrate the assembling and picking up of nano-needles, which indicate potential applications in intracellular endoscopy, high resoln. scanning tips, on-chip nanophotonic devices, etc.
- 715Zhu, H.; Masson, J.-F.; Bazuin, C. G. Templating Gold Nanoparticles on Nanofibers Coated with a Block Copolymer Brush for Nanosensor Applications. ACS Applied Nano Materials 2020, 3, 516– 529, DOI: 10.1021/acsanm.9b02081Google ScholarThere is no corresponding record for this reference.
- 716Zhao, X.; Luo, X.; Bazuin, C. G.; Masson, J.-F. In Situ Growth of AuNPs on Glass Nanofibers for SERS Sensors. ACS Appl. Mater. & Interfaces 2020, 12, 55349– 55361, DOI: 10.1021/acsami.0c15311Google ScholarThere is no corresponding record for this reference.
- 717Ricci, M.; Fortuni, B.; Vitale, R.; Zhang, Q.; Fujita, Y.; Toyouchi, S.; Lu, G.; Rocha, S.; Inose, T.; Uji-i, H. Gold-Etched Silver Nanowire Endoscopy: Toward a Widely Accessible Platform for Surface-Enhanced Raman Scattering-Based Analysis in Living Cells. Anal. Chem. 2021, 93, 5037– 5045, DOI: 10.1021/acs.analchem.0c04120Google Scholar717Gold-Etched Silver Nanowire Endoscopy: Toward a Widely Accessible Platform for Surface-Enhanced Raman Scattering-Based Analysis in Living CellsRicci, Monica; Fortuni, Beatrice; Vitale, Raffaele; Zhang, Qiang; Fujita, Yasuhiko; Toyouchi, Shuichi; Lu, Gang; Rocha, Susana; Inose, Tomoko; Uji-i, HiroshiAnalytical Chemistry (Washington, DC, United States) (2021), 93 (12), 5037-5045CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Recently, our group introduced the use of silver nanowires (AgNWs) as novel non-invasive endoscopic probes for detecting intracellular Raman signals. This method, although innovative and promising, relies exclusively on the plasmonic waveguiding effect for signal enhancement. It, therefore, requires sophisticated operational tools and protocols, drastically limiting its applicability. Herein, an advanced strategy is offered to significantly enhance the performance of these endoscopic probes, making this approach widely accessible and versatile for cellular studies. By uniformly forming gold structures on the smooth AgNW surface via a galvanic replacement reaction, the d. of the light coupling points along the whole probe surface is drastically increased, enabling high surface-enhanced Raman scattering (SERS) efficiency upon solely focusing the excitation light on the gold-etched AgNW. The applicability of these gold-etched AgNW probes for mol. sensing in cells is demonstrated by detecting site-specific and high-resolved SERS spectra of cell compartment-labeling dyes, namely, 4',6-diamidino-2-phenylindole in the nucleus and 3,3'-dioctadecyloxacarbocyanine on the membrane. The remarkable spectral sensitivity achieved provides essential structural information of the analytes, indicating the overall potential of the proposed approach for cellular studies of drug interactions with biomol. items.
- 718Pan, X.-T.; Yang, X.-Y.; Mao, T.-Q.; Liu, K.; Chen, Z.-Z.; Ji, L.-N.; Jiang, D.-C.; Wang, K.; Gu, Z.-Z.; Xia, X.-H. Super-Long SERS Active Single Silver Nanowires for Molecular Imaging in 2D and 3D Cell Culture Models. Biosensors 2022, 12, 875, DOI: 10.3390/bios12100875Google Scholar718Super-Long SERS Active Single Silver Nanowires for Molecular Imaging in 2D and 3D Cell Culture ModelsPan, Xiao-Tong; Yang, Xuan-Ye; Mao, Tian-Qi; Liu, Kang; Chen, Zao-Zao; Ji, Li-Na; Jiang, De-Chen; Wang, Kang; Gu, Zhong-Ze; Xia, Xing-HuaBiosensors (2022), 12 (10), 875CODEN: BIOSHU; ISSN:2079-6374. (MDPI AG)Establishing a systematic mol. information anal. strategy for cell culture models is of great significance for drug development and tissue engineering technologies. Here, we fabricated single silver nanowires with high surface-enhanced Raman scattering activity to ext. SERS spectra in situ from two-dimensional (2D) and three-dimensional (3D) cell culture models. The silver nanowires were super long, flexible and thin enough to penetrate through multiple cells. A single silver nanowire was used in combination with a four-dimensional microcontroller as a cell endoscope for spectrally analyzing the components in cell culture models. Then, we adopted a machine learning algorithm to analyze the obtained spectra. Our results show that the abundance of proteins differs significantly between the 2D and 3D models, and that nucleic acid-rich and protein-rich regions can be distinguished with satisfactory accuracy.
- 719Fortuni, B.; Ricci, M.; Vitale, R.; Inose, T.; Zhang, Q.; Hutchison, J. A.; Hirai, K.; Fujita, Y.; Toyouchi, S.; Krzyzowska, S.; Van Zundert, I.; Rocha, S.; Uji-i, H. SERS Endoscopy for Monitoring Intracellular Drug Dynamics. ACS Sens. 2023, 8, 2340– 2347, DOI: 10.1021/acssensors.3c00394Google ScholarThere is no corresponding record for this reference.
- 720Zhang, Q.; Murasugi, T.; Watanabe, K.; Wen, H.; Tian, Y.; Ricci, M.; Rocha, S.; Inose, T.; Kasai, H.; Taemaitree, F.; Uji-i, H.; Hirai, K.; Fortuni, B. Selective Detection of Intracellular Drug Metabolism by Metal-Organic Framework-Coated Plasmonic Nanowire. Advanced Optical Materials 2023, 11, 2300856, DOI: 10.1002/adom.202300856Google ScholarThere is no corresponding record for this reference.
- 721Chisanga, M.; Masson, J.-F. Machine Learning–Driven SERS Nanoendoscopy and Optophysiology. Annual Review of Analytical Chemistry 2024, 17, 313– 338, DOI: 10.1146/annurev-anchem-061622-012448Google ScholarThere is no corresponding record for this reference.
- 722Boudries, R.; Williams, H.; Paquereau--Gaboreau, S.; Bashir, S.; Hojjat Jodaylami, M.; Chisanga, M.; Trudeau, L.-É.; Masson, J.-F. Surface-Enhanced Raman Scattering Nanosensing and Imaging in Neuroscience. ACS Nano 2024, 18, 22620– 22647, DOI: 10.1021/acsnano.4c05200Google ScholarThere is no corresponding record for this reference.
- 723Stone, N.; Faulds, K.; Graham, D.; Matousek, P. Prospects of Deep Raman Spectroscopy for Noninvasive Detection of Conjugated Surface Enhanced Resonance Raman Scattering Nanoparticles Buried within 25 mm of Mammalian Tissue. Anal. Chem. 2010, 82, 3969– 3973, DOI: 10.1021/ac100039cGoogle Scholar723Prospects of Deep Raman Spectroscopy for Noninvasive Detection of Conjugated Surface Enhanced Resonance Raman Scattering Nanoparticles Buried within 25 mm of Mammalian TissueStone, Nicholas; Faulds, Karen; Graham, Duncan; Matousek, PavelAnalytical Chemistry (Washington, DC, United States) (2010), 82 (10), 3969-3973CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)This letter discusses the potential of deep Raman spectroscopy, surface enhanced spatially offset Raman spectroscopy (SESORS and its variants), for noninvasively detecting small, deeply buried lesions using surface enhanced resonance Raman scattering (SERRS) active nanoparticles. An exptl. demonstration of this concept is performed in transmission Raman geometry. This method opens prospects for in vivo, noninvasive, specific detection of mol. changes assocd. with disease up to depths of several centimeters representing significant improvement over traditionally detected Raman signals by 2 orders of magnitude. The disease specific signals can be achieved using uniquely tagged nanoparticles conjugated to target mols., e.g., antibodies for prodn. of the SERRS signal. This provides the mol. specific signal which is many orders of magnitude greater than normal biol. Raman signals and can be easily multiplexed. To date, there have been no studies demonstrating the viability of deep Raman spectroscopy coupled to surface enhanced techniques for detecting low concns. of mols. of interest at depths of greater than 5.5 mm in tissue. Such a breakthrough would open a host of new applications in medical diagnoses. Here the authors propose to facilitate such capability by combining SERRS (as a probe for disease specific changes) with deep Raman spectroscopy techniques. This permits noninvasive measurement of Raman signatures from conjugated SERRS nanoparticles at clin. relevant concns. through tissues of between 15 and 25 mm thick.
- 724Stone, N.; Kerssens, M.; Lloyd, G. R.; Faulds, K.; Graham, D.; Matousek, P. Surface enhanced spatially offset Raman spectroscopic (SESORS) imaging – the next dimension. Chemical Science 2011, 2, 776– 780, DOI: 10.1039/c0sc00570cGoogle Scholar724Surface enhanced spatially offset Raman spectroscopic (SESORS) imaging - the next dimensionStone, Nicholas; Kerssens, Marleen; Lloyd, Gavin Rhys; Faulds, Karen; Graham, Duncan; Matousek, PavelChemical Science (2011), 2 (4), 776-780CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)SESORS - Surface enhanced spatially offset Raman spectroscopy-imaging is explored for the first time in this study. Multiplexed surface enhanced Raman scattering (SERS) signals have been recovered non-invasively from a depth of 20 mm in tissues for the first time and reconstructed to produce a false color image. Four unique 'flavours' of SERS nanoparticles (NPs) were injected into a 20 × 50 × 50 mm porcine tissue block at the corners of a 10 mm square. A transmission Raman data cube was acquired over an 11 × 11 pixel grid made up of 2 mm steps. The signals were reconstructed using the unique peak intensities of each of the nanoparticles. A false color image of the relative signal levels was produced, demonstrating the capability of multiplexed imaging of SERS nanoparticles using deep Raman spectroscopy. A secondary but no less significant achievement was to demonstrate that Raman signals from SERS nanoparticles can be recovered non-invasively from samples of the order of 45-50 mm thick. This is a significant step forward in the ability to detect and identify vibrational fingerprints within tissue and offers the opportunity to adapt these particles and this approach into a clin. setting for disease diagnosis.
- 725Matousek, P.; Clark, I. P.; Draper, E. R. C.; Morris, M. D.; Goodship, A. E.; Everall, N.; Towrie, M.; Finney, W. F.; Parker, A. W. Subsurface Probing in Diffusely Scattering Media Using Spatially Offset Raman Spectroscopy. Appl. Spectrosc. 2005, 59, 393– 400, DOI: 10.1366/0003702053641450Google Scholar725Subsurface probing in diffusely scattering media using spatially offset Raman spectroscopyMatousek, P.; Clark, I. P.; Draper, E. R. C.; Morris, M. D.; Goodship, A. E.; Everall, N.; Towrie, M.; Finney, W. F.; Parker, A. W.Applied Spectroscopy (2005), 59 (4), 393-400CODEN: APSPA4; ISSN:0003-7028. (Society for Applied Spectroscopy)We describe a simple methodol. for the effective retrieval of Raman spectra of subsurface layers in diffusely scattering media. The technique is based on the collection of Raman scattered light from surface regions that are laterally offset away from the excitation laser spot on the sample. The Raman spectra obtained in this way exhibit a variation in relative spectral intensities of the surface and subsurface layers of the sample being investigated. The data set is processed using a multivariate data anal. to yield pure Raman spectra of the individual sample layers, providing a method for the effective elimination of surface Raman scatter. The methodol. is applicable to the retrieval of pure Raman spectra from depths well in excess of those accessible with conventional confocal microscopy. In this first feasibility study we have differentiated between surface and subsurface Raman signals within a diffusely scattering sample composed of two layers: trans-stilbene powder beneath a 1 mm thick over-layer of PMMA (poly(Me methacrylate)) powder. The improvement in contrast of the subsurface trans-stilbene layer without numerical processing was 19 times. The potential applications include biomedical subsurface probing of specific tissues through different overlying tissues such as assessment of bone quality through skin, providing an effective noninvasive means of screening for bone degeneration, other skeletal disease diagnosis, and dermatol. studies, as well as materials and catalyst research.
- 726Mosca, S.; Dey, P.; Salimi, M.; Gardner, B.; Palombo, F.; Stone, N.; Matousek, P. Spatially Offset Raman Spectroscopy─How Deep?. Anal. Chem. 2021, 93, 6755– 6762, DOI: 10.1021/acs.analchem.1c00490Google Scholar726Spatially Offset Raman Spectroscopy-How Deep?Mosca, Sara; Dey, Priyanka; Salimi, Marzieh; Gardner, Benjamin; Palombo, Francesca; Stone, Nick; Matousek, PavelAnalytical Chemistry (Washington, DC, United States) (2021), 93 (17), 6755-6762CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Spatially offset Raman spectroscopy (SORS) is a technique for interrogating the subsurface compn. of turbid samples noninvasively. This study generically addresses a fundamental question relevant to a wide range of SORS studies, which is how deep SORS probes for any specific spatial offset when analyzing a turbid sample or, in turn, what magnitude of spatial offset one should select to probe a specific depth. This issue is addressed by using Monte Carlo simulations, under the assumption of negligible absorption, which establishes that the key parameter governing the extent of the probed zone for a point-like illumination and point-like collection SORS geometry is the reduced scattering coeff. of the medium. This can either be deduced from literature data or directly estd. from a SORS measurement by evaluating the Raman intensity profile from multiple spatial offsets. Once this is known, the extent of the probed zone can be detd. for any specific SORS spatial offset using the Monte Carlo simulation results presented here. The proposed method was tested using exptl. data on stratified samples by analyzing the signal detected from a thin layer that was moved through a stack of layers using both non-absorbing and absorbing samples. The proposed simple methodol. provides important addnl. information on SORS measurements with direct relevance to a wide range of SORS applications including biomedical, pharmaceutical, security, forensics, and cultural heritage.
- 727Mosca, S.; Conti, C.; Stone, N.; Matousek, P. Spatially offset Raman spectroscopy. Nat. Rev. Methods Prim. 2021, 1, 21, DOI: 10.1038/s43586-021-00019-0Google ScholarThere is no corresponding record for this reference.
- 728Moody, A. S.; Payne, T. D.; Barth, B. A.; Sharma, B. Surface-enhanced spatially-offset Raman spectroscopy (SESORS) for detection of neurochemicals through the skull at physiologically relevant concentrations. Analyst 2020, 145, 1885– 1893, DOI: 10.1039/C9AN01708AGoogle Scholar728Surface-enhanced spatially-offset Raman spectroscopy (SESORS) for detection of neurochemicals through the skull at physiologically relevant concentrationsMoody, Amber S.; Payne, Taylor D.; Barth, Brian A.; Sharma, BhavyaAnalyst (Cambridge, United Kingdom) (2020), 145 (5), 1885-1893CODEN: ANALAO; ISSN:0003-2654. (Royal Society of Chemistry)Detection techniques for neurotransmitters that are rapid, label-free, and non-invasive are needed to move towards earlier diagnosis of neurol. disease. Surface-enhanced Raman spectroscopy (SERS) allows for sensitive and selective detection of target analytes. The combination of SERS with spatially offset Raman spectroscopy (SORS) in a technique termed surface enhanced spatially offset Raman spectroscopy (SESORS) permits a sensitive and selective detection of neurotransmitters through the skull. Here, the authors present the SESORS detection of individual neurotransmitters and mixts. of neurotransmitters at physiol. relevant concns., while also establishing limits of detection.
- 729Nicolson, F.; Andreiuk, B.; Andreou, C.; Hsu, H.-T.; Rudder, S.; Kircher, M. F. Non-invasive In Vivo Imaging of Cancer Using Surface-Enhanced Spatially Offset Raman Spectroscopy (SESORS). Theranostics 2019, 9, 5899– 5913, DOI: 10.7150/thno.36321Google Scholar729Non-invasive in vivo imaging of cancer using surface-enhanced spatially offset Raman spectroscopy (SESORS)Nicolson, Fay; Andreiuk, Bohdan; Andreou, Chrysafis; Hsu, Hsiao-Ting; Rudder, Scott; Kircher, Moritz F.Theranostics (2019), 9 (20), 5899-5913CODEN: THERDS; ISSN:1838-7640. (Ivyspring International Publisher)The goal of imaging tumors at depth with high sensitivity and specificity represents a significant challenge in the field of biomedical optical imaging. 'Surface enhanced Raman scattering' (SERS) nanoparticles (NPs) have been employed as image contrast agents and can be used to specifically target cells in vivo. By tracking their unique "fingerprint" spectra, it becomes possible to det. their precise location. However, while the detection of SERS NPs is very sensitive and specific, conventional Raman spectroscopy imaging devices are limited in their inability to probe through tissue depths of more than a few millimetres, due to scattering and absorption of photons by biol. tissues. Here, we combine the use of "Spatially Offset Raman spectroscopy" (SORS) with that of "surface-enhanced resonance Raman spectroscopy" (SERRS) in a technique known as "surface enhanced spatially offset resonance Raman spectroscopy" (SESO(R)RS) to image deep-seated glioblastoma multiforme (GBM) tumors in vivo in mice through the intact skull. A SORS imaging system was built inhouse. Proof of concept SORS imaging was achieved using a PTFE-skull-tissue phantom. Imaging of GBMs in the RCAS-PDGF/N-tva transgenic mouse model was achieved through the use of gold nanostars functionalized with a resonant Raman reporter to create SERRS nanostars. These were then encapsulated in a thin silica shell and functionalized with a cyclic-RGDyK peptide to yield integrin-targeting SERRS nanostars. Non-invasive in vivo SORS image acquisition of the integrin-targeted nanostars was then performed in living mice under general anesthesia. Conventional non-SORS imaging was used as a direct comparison. Using a low power d. laser, GBMs were imaged via SESORRS in mice (n = 5) and confirmed using MRI and histopathol. The results demonstrate that via utilization of the SORS approach, it is possible to acquire clear and distinct Raman spectra from deep-seated GBMs in mice in vivo through the skull. SESORRS images generated using classical least squares outlined the tumors with high precision as confirmed via MRI and histol. Unlike SESORRS, conventional Raman imaging of the same areas did not provide a clear delineation of the tumor. To the best of our knowledge this is the first report of in vivo SESO(R)RS imaging. In a relevant brain tumor mouse model we demonstrate that this technique can overcome the limitations of conventional Raman imaging with regards to penetration depth. This work therefore represents a significant step forward in the potential clin. translation of SERRS nanoparticles for high precision cancer imaging.
- 730Gardner, B.; Matousek, P.; Stone, N. Subsurface Chemically Specific Measurement of pH Levels in Biological Tissues Using Combined Surface-Enhanced and Deep Raman. Anal. Chem. 2019, 91, 10984– 10987, DOI: 10.1021/acs.analchem.9b01015Google Scholar730Subsurface Chemically Specific Measurement of pH Levels in Biological Tissues Using Combined Surface-Enhanced and Deep RamanGardner, Benjamin; Matousek, Pavel; Stone, NicholasAnalytical Chemistry (Washington, DC, United States) (2019), 91 (17), 10984-10987CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)There is much interest in using nanosensors to monitor biol. relevant species such as glucose, or cellular pH, as these often become dysregulated in diseases such as cancer. This information is often inaccessible at depth in biol. tissue, due to the highly scattering nature of tissue. Here we show that gold nanoparticles labeled with pH-sensitive reporter mols. can monitor pH at depth in biol. tissues. This was achieved using deep Raman spectroscopy (spatially offset Raman and transmission Raman) in combination with surface-enhanced Raman spectroscopy, allowing chem. information to be retrieved significantly deeper than conventional Raman spectroscopy permits. Combining these approaches with chemometrics enabled pH changes to be monitored with an error of ±∼0.1 pH units noninvasively through 22 mm of soft tissue. This development opens the opportunity for the next generation of light-based medical diagnostic methods, such as monitoring of cancers, known to significantly alter pH levels.
- 731Gardner, B.; Stone, N.; Matousek, P. Noninvasive simultaneous monitoring of pH and depth using surface-enhanced deep Raman spectroscopy. J. Raman Spectrosc. 2020, 51, 1078– 1082, DOI: 10.1002/jrs.5875Google ScholarThere is no corresponding record for this reference.
- 732Liberti, M. V.; Locasale, J. W. The Warburg Effect: How Does it Benefit Cancer Cells?. Trends Biochem. Sci. 2016, 41, 211– 218, DOI: 10.1016/j.tibs.2015.12.001Google Scholar732The Warburg Effect: How Does it Benefit Cancer Cells?Liberti, Maria V.; Locasale, Jason W.Trends in Biochemical Sciences (2016), 41 (3), 211-218CODEN: TBSCDB; ISSN:0968-0004. (Elsevier Ltd.)Cancer cells rewire their metab. to promote growth, survival, proliferation, and long-term maintenance. The common feature of this altered metab. is the increased glucose uptake and fermn. of glucose to lactate. This phenomenon is obsd. even in the presence of completely functioning mitochondria and, together, is known as the 'Warburg Effect'. The Warburg Effect has been documented for over 90 years and extensively studied over the past 10 years, with thousands of papers reporting to have established either its causes or its functions. Despite this intense interest, the function of the Warburg Effect remains unclear. Here, we analyze several proposed explanations for the function of Warburg Effect, emphasize their rationale, and discuss their controversies.
- 733Gardner, B.; Stone, N.; Matousek, P. Non-invasive chemically specific measurement of subsurface temperature in biological tissues using surface-enhanced spatially offset Raman spectroscopy. Faraday Discuss. 2016, 187, 329– 339, DOI: 10.1039/C5FD00154DGoogle Scholar733Non-invasive chemically specific measurement of subsurface temperature in biological tissues using surface-enhanced spatially offset Raman spectroscopyGardner, Benjamin; Stone, Nicholas; Matousek, PavelFaraday Discussions (2016), 187 (Advanced Vibrational Spectroscopy for Biomedical Applications), 329-339CODEN: FDISE6; ISSN:1359-6640. (Royal Society of Chemistry)Here we demonstrate for the first time the viability of characterizing non-invasively the subsurface temp. of SERS nanoparticles embedded within biol. tissues using spatially offset Raman spectroscopy (SORS). The proposed anal. method (T-SESORS) is applicable in general to diffusely scattering (turbid) media and features high sensitivity and high chem. selectivity. The method relies on monitoring the Stokes and anti-Stokes bands of SERS nanoparticles in depth using SORS. The approach has been conceptually demonstrated using a SORS variant, transmission Raman spectroscopy (TRS), by measuring subsurface temps. within a slab of porcine tissue (5 mm thick). Root-mean-square errors (RMSEs) of 0.20 °C were achieved when measuring temps. over ranges between 25 and 44 °C. This unique capability complements the array of existing, predominantly surface-based, temp. monitoring techniques. It expands on a previously demonstrated SORS temp. monitoring capability by adding extra sensitivity stemming from SERS to low concn. analytes. The technique paves the way for a wide range of applications including subsurface, chem.-specific, non-invasive temp. anal. within turbid translucent media including: the human body, subsurface monitoring of chem. (e.g. catalytic) processes in manuf. quality and process control and research. Addnl., the method opens prospects for control of thermal treatment of cancer in vivo with direct non-invasive feedback on the temp. of mediating plasmonic nanoparticles.
- 734Nicolson, F.; Andreiuk, B.; Lee, E.; O’Donnell, B.; Whitley, A.; Riepl, N.; Burkhart, D. L.; Cameron, A.; Protti, A.; Rudder, S.; Yang, J.; Mabbott, S.; Haigis, K. M. In vivo imaging using surface enhanced spatially offset raman spectroscopy (SESORS): balancing sampling frequency to improve overall image acquisition. npj Imaging 2024, 2, 7, DOI: 10.1038/s44303-024-00011-9Google ScholarThere is no corresponding record for this reference.
- 735Gardner, B.; Stone, N.; Matousek, P. Noninvasive Determination of Depth in Transmission Raman Spectroscopy in Turbid Media Based on Sample Differential Transmittance. Anal. Chem. 2017, 89, 9730– 9733, DOI: 10.1021/acs.analchem.7b01469Google Scholar735Noninvasive Determination of Depth in Transmission Raman Spectroscopy in Turbid Media Based on Sample Differential TransmittanceGardner, Benjamin; Stone, Nicholas; Matousek, PavelAnalytical Chemistry (Washington, DC, United States) (2017), 89 (18), 9730-9733CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Here the authors propose a simple noninvasive approach to det. the depth of a buried object using transmission Raman spectroscopy. In accordance with theory, the photons arising from spectral peaks that are suitably sepd. will be subjected to different optical properties in the media through which they travel. These differences can impact the relative intensities of Raman peaks as a function of the transmission path length, thereby the depth of signal generation is inherently encoded in the spectra. In a proof-of-concept study, through only external calibrations, it was possible to accurately predict the depth of Polytetrafluoroethylene (PTFE) layer purely on the basis of relative intensity of two peaks in a predominantly absorbing soln. Indian ink (0.1 μL/mL; RMSE 0.42 mm) and a scattering soln. (RMSE 0.50 mm). This simple approach offers the possibility to noninvasively identify the depth of a buried object, such as breast calcifications, using simple transmission measurement geometries for the first time.
- 736Mosca, S.; Dey, P.; Tabish, T. A.; Palombo, F.; Stone, N.; Matousek, P. Determination of inclusion depth in ex vivo animal tissues using surface enhanced deep Raman spectroscopy. J. Biophotonics 2020, 13, e201960092, DOI: 10.1002/jbio.201960092Google ScholarThere is no corresponding record for this reference.
- 737Mosca, S.; Dey, P.; Salimi, M.; Palombo, F.; Stone, N.; Matousek, P. Non-invasive depth determination of inclusion in biological tissues using spatially offset Raman spectroscopy with external calibration. Analyst 2020, 145, 7623– 7629, DOI: 10.1039/D0AN01292KGoogle Scholar737Non-invasive depth determination of inclusion in biological tissues using spatially offset Raman spectroscopy with external calibrationMosca, Sara; Dey, Priyanka; Salimi, Marzieh; Palombo, Francesca; Stone, Nick; Matousek, PavelAnalyst (Cambridge, United Kingdom) (2020), 145 (23), 7623-7629CODEN: ANALAO; ISSN:0003-2654. (Royal Society of Chemistry)Spatially offset Raman spectroscopy (SORS) allows chem. characterization of biol. tissues at depths of up to two orders of magnitude greater than conventional Raman spectroscopy. In this study, we demonstrate the use of SORS for the non-invasive prediction of depth of an inclusion within turbid media (e.g. biol. tissues) using only external calibration data sets, thus extending our previous approach that required internal calibration. As with the previous methodol., the concept is based on relative changes in Raman band intensities of the inclusion that are directly related to the path length of Raman photons travelling through the medium thereby encoding the information of depth of the inclusion. However, here the calibration model is created using data only from external measurements performed at the tissue surface. This new approach facilitates a fully non-invasive methodol. applicable potentially to in vivo medical diagnosis without any a priori knowledge. Monte Carlo simulations of photon propagation have been used to provide insight into the relationship between the spatial offset and the photon path lengths inside the tissues enabling one to derive a general scaling factor permitting the use of spatial offset measurements for the depth prediction. The approach was validated by predicting the depth of surface-enhanced Raman scattering (SERS) labeled nanoparticles (NPs) acting as inclusions inside a slab of ex vivo porcine tissue yielding an av. root mean square error of prediction of 7.3% with respect to the overall tissue thickness. Our results pave the way for future non-invasive deep Raman spectroscopy in vivo by enabling, for example, the localisation of cancer lesions or cancer biomarkers in early disease diagnosis and targeted treatments.
- 738Berry, M. E.; McCabe, S. M.; Sloan-Dennison, S.; Laing, S.; Shand, N. C.; Graham, D.; Faulds, K. Tomographic Imaging and Localization of Nanoparticles in Tissue Using Surface-Enhanced Spatially Offset Raman Spectroscopy. ACS Appl. Mater. & Interfaces 2022, 14, 31613– 31624, DOI: 10.1021/acsami.2c05611Google ScholarThere is no corresponding record for this reference.
- 739Mosca, S.; Mehta, M.; Skinner, W. H.; Gardner, B.; Palombo, F.; Stone, N.; Matousek, P. Active Surface-Enhanced Raman Spectroscopy (SERS): A Novel Concept for Enhancing Signal Contrast in Complex Matrices Using External Perturbation. Appl. Spectrosc. 2024, 37028241267898, DOI: 10.1177/00037028241267898Google ScholarThere is no corresponding record for this reference.
- 740Mellor, R. D.; Schätzlein, A. G.; Uchegbu, I. F. Development of Bio-Functionalized, Raman Responsive, and Potentially Excretable Gold Nanoclusters. Nanomaterials 2021, 11, 2181, DOI: 10.3390/nano11092181Google ScholarThere is no corresponding record for this reference.
- 741Yu, J. H.; Jeong, M. S.; Cruz, E. O.; Alam, I. S.; Tumbale, S. K.; Zlitni, A.; Lee, S. Y.; Park, Y. I.; Ferrara, K.; Kwon, S.-H.; Gambhir, S. S.; Rao, J. Highly Excretable Gold Supraclusters for Translatable In Vivo Raman Imaging of Tumors. ACS Nano 2023, 17, 2554– 2567, DOI: 10.1021/acsnano.2c10378Google ScholarThere is no corresponding record for this reference.
- 742Buckley, K.; Matousek, P. Recent advances in the application of transmission Raman spectroscopy to pharmaceutical analysis. J. Pharm. Biomed. Anal. 2011, 55, 645– 652, DOI: 10.1016/j.jpba.2010.10.029Google Scholar742Recent advances in the application of transmission Raman spectroscopy to pharmaceutical analysisBuckley, Kevin; Matousek, PavelJournal of Pharmaceutical and Biomedical Analysis (2011), 55 (4), 645-652CODEN: JPBADA; ISSN:0731-7085. (Elsevier B.V.)A review. This article reviews recent advances in transmission Raman spectroscopy and its applications, from the perspective of pharmaceutical anal. The emerging concepts enable rapid non-invasive volumetric anal. of pharmaceutical formulations and could lead to many important applications in pharmaceutical settings, including quant. bulk anal. of intact pharmaceutical tablets and capsules in quality and process control.
- 743Dey, P.; Vaideanu, A.; Mosca, S.; Salimi, M.; Gardner, B.; Palombo, F.; Uchegbu, I.; Baumberg, J.; Schatzlein, A.; Matousek, P.; Stone, N. Surface enhanced deep Raman detection of cancer tumour through 71 mm of heterogeneous tissue. Nanotheranostics 2022, 6, 337– 349, DOI: 10.7150/ntno.71510Google ScholarThere is no corresponding record for this reference.
- 744Bi, X.; Gu, Y.; Ye, J. Ag-Coated Au Nanopetals: Dual-Type Single-Nanoparticle Detection of Gap-Enhanced Resonance Raman Tags. ACS Applied Nano Materials 2020, 3, 6987– 6995, DOI: 10.1021/acsanm.0c01317Google ScholarThere is no corresponding record for this reference.
- 745Zhang, Y.; Lin, L.; He, J.; Ye, J. Optical penetration of surface-enhanced micro-scale spatial offset Raman spectroscopy in turbid gel and biological tissue. J. Innov. Opt. Health Sci. 2021, 14, 2141001, DOI: 10.1142/S1793545821410017Google ScholarThere is no corresponding record for this reference.
- 746Zhang, Y.; Lin, L.; Ye, J. A rapid and universal method for depth estimation of lesions in heterogeneous tissues via photosafe ratiometric transmission Raman spectroscopy. VIEW 2023, 4, 20230022, DOI: 10.1002/VIW.20230022Google ScholarThere is no corresponding record for this reference.
- 747Wu, Z.; Deng, B.; Zhou, Y.; Xie, H.; Zhang, Y.; Lin, L.; Ye, J. Non-Invasive Detection, Precise Localization, and Perioperative Navigation of In Vivo Deep Lesions Using Transmission Raman Spectroscopy. Advanced Science 2023, 10, 2301721, DOI: 10.1002/advs.202301721Google ScholarThere is no corresponding record for this reference.
- 748Demers, J. L.; Esmonde-White, F. W.; Esmonde-White, K. A.; Morris, M. D.; Pogue, B. W. Next-generation Raman tomography instrument for non-invasive in vivo bone imaging. Biomed Opt Express 2015, 6, 793– 806, DOI: 10.1364/BOE.6.000793Google Scholar748Next-generation Raman tomography instrument for non-invasive in vivo bone imagingDemers Jennifer-Lynn H; Esmonde-White Francis W L; Esmonde-White Karen A; Morris Michael D; Pogue Brian WBiomedical optics express (2015), 6 (3), 793-806 ISSN:2156-7085.Combining diffuse optical tomography methods with Raman spectroscopy of tissue provides the ability for in vivo measurements of chemical and molecular characteristics, which have the potential for being useful in diagnostic imaging. In this study a system for Raman tomography was developed and tested. A third generation microCT coupled system was developed to combine 10 detection fibers and 5 excitation fibers with laser line filtering and a Cytop reference signal. Phantom measurements of hydroxyapatite concentrations from 50 to 300 mg/ml had a linear response. Fiber placement and experiment design was optimized using cadaver animals with live animal measurements acquired to validate the systems capabilities. Promising results from the initial animal experiments presented here, pave the way for a study of longitudinal measurements during fracture healing and the scaling of the Raman tomography system towards human measurements.
- 749Xie, H.; Zhang, Y.; Wu, Z.; Bao, Z.; Lin, L.; Ye, J. Locating Three-Dimensional Position of Deep-Seated SERS Phantom Lesions in Thick Tissues Using Tomographic Transmission Raman Spectroscopy. ACS Appl. Mater. Interfaces 2023, 15, 44665– 44675, DOI: 10.1021/acsami.3c07792Google ScholarThere is no corresponding record for this reference.
- 750Stepula, E.; Walther, A. R.; Jensen, M.; Mehrotra, D. R.; Yuan, M. H.; Pedersen, S. V.; Kumar, V.; Gentleman, E.; Albro, M. B.; Hedegaard, M. A. B.; Bergholt, M. S. Label-free 3D molecular imaging of living tissues using Raman spectral projection tomography. Nat. Commun. 2024, 15, 7717, DOI: 10.1038/s41467-024-51616-yGoogle ScholarThere is no corresponding record for this reference.
- 751Czaja, A.; Jiang, A. J.; Blanco, M. Z.; Eremina, O. E.; Zavaleta, C. A Raman topography imaging method toward assisting surgical tumor resection. npj Imaging 2024, 2, 2, DOI: 10.1038/s44303-024-00006-6Google ScholarThere is no corresponding record for this reference.
- 752Wang, C.; Wang, C.; Li, J.; Tu, Z.; Gu, B.; Wang, S. Ultrasensitive and multiplex detection of four pathogenic bacteria on a bi-channel lateral flow immunoassay strip with three-dimensional membrane-like SERS nanostickers. Biosens. Bioelectron. 2022, 214, 114525, DOI: 10.1016/j.bios.2022.114525Google Scholar752Ultrasensitive and multiplex detection of four pathogenic bacteria on a bi-channel lateral flow immunoassay strip with three-dimensional membrane-like SERS nanostickersWang, Chongwen; Wang, Chaoguang; Li, Jiaxuan; Tu, Zhijie; Gu, Bing; Wang, ShengqiBiosensors & Bioelectronics (2022), 214 (), 114525CODEN: BBIOE4; ISSN:0956-5663. (Elsevier B.V.)A lateral flow immunoassay (LFA) technique for sensitive and multiplexed on-site detection of bacteria remains a challenge. Here, we develop a bi-channel surface-enhanced Raman scattering (SERS)-based LFA by using three-dimensional membrane-like SERS tags as nanostickers (named GO@Au/Ag) for direct and ultrasensitive anal. of multiple pathogens in a single test. The grafting of numerous Ag satellites onto nanosticker significantly increased the relative surface area for bacteria binding and generated efficient SERS hotspots over large area to improve the sensing sensitivity. Antibody-labeled GO@Au/Ag nanostickers can rapidly stick onto the target bacteria and generate superior SERS signals and fluidity on the paper strip, thus conquering the adverse effect of bacteria size and improving the multiplex anal. ability of LFA. The integration of two different Raman reporter mols. into nanostickers allows simultaneous detection of four pathogens on two test lines, which significantly simplifies the reading process of SERS signals. The proposed biosensor can quant. detect four different bacteria in real clin. samples with low detection limit (9 cells mL-1 level), short assay time (20 min), high accuracy and excellent stability, indicating its great application potential for on-site detection of pathogens.
- 753Ye, Z.; Lin, L.; Tan, Z.; Zeng, Y.-J.; Ruan, S.; Ye, J. Sub-100 nm multi-shell bimetallic gap-enhanced Raman tags. Appl. Surf. Sci. 2019, 487, 1058– 1067, DOI: 10.1016/j.apsusc.2019.05.200Google Scholar753Sub-100 nm multi-shell bimetallic gap-enhanced Raman tagsYe, Zhixiang; Lin, Li; Tan, Ziyang; Zeng, Yu-Jia; Ruan, Shuangchen; Ye, JianApplied Surface Science (2019), 487 (), 1058-1067CODEN: ASUSEE; ISSN:0169-4332. (Elsevier B.V.)Gap-enhanced Raman tags (GERTs) with built-in Raman mols. show excellent surface-enhanced Raman scattering (SERS) performance and great potential for biomedical applications. In this work, we add a silver (Ag) shell to gold (Au) single-shell GERTs (Au@BDT@Au) to form Au-Ag hybrid multi-shell nanoparticles. It is found that this modification enhances the SERS performance of the NPs and that the thickness of the Ag shell is a key factor in detg. the enhancement. Double-shell bimetallic GERTs with a Au core, Au shell and exterior 2 nm-thickness silver shell (Au@BDT@Au@BDT@Ag) show the best SERS performance and good photostability. Moreover, we utilize the double-shell bimetallic GERTs to develop a new kind of SERS-based lateral flow immunoassay (LFIA), acheiving limit of detection as low as 0.7 mIU/mL (0.077 ng/mL). We demonstrated a simple way to fabricate sub-100 nm multi-shell bimetallic GERTs for use as SERS probes with strong Raman signals with potential for in vivo and in vitro application as bioimaging and biosensing probes.
- 754Zhang, D.; Huang, L.; Liu, B.; Ge, Q.; Dong, J.; Zhao, X. Rapid and Ultrasensitive Quantification of Multiplex Respiratory Tract Infection Pathogen via Lateral Flow Microarray based on SERS Nanotags. Theranostics 2019, 9, 4849– 4859, DOI: 10.7150/thno.35824Google ScholarThere is no corresponding record for this reference.
- 755Zhang, D.; Huang, L.; Liu, B.; Su, E.; Chen, H.-Y.; Gu, Z.; Zhao, X. Quantitative detection of multiplex cardiac biomarkers with encoded SERS nanotags on a single T line in lateral flow assay. Sens. Actuators, B 2018, 277, 502– 509, DOI: 10.1016/j.snb.2018.09.044Google Scholar755Quantitative detection of multiplex cardiac biomarkers with encoded SERS nanotags on a single T line in lateral flow assayZhang, Di; Huang, Li; Liu, Bing; Su, Enben; Chen, Hong-Yuan; Gu, Zhongze; Zhao, XiangweiSensors and Actuators, B: Chemical (2018), 277 (), 502-509CODEN: SABCEB; ISSN:0925-4005. (Elsevier B.V.)Quick and accurate quantification of multiple biomarkers is quite a challenge in high throughput detection. Herein, we developed a novel lateral flow assay (LFA) based on Raman dyes (RDs) encoded core-shell surface enhanced Raman scattering (SERS) nanotags for rapid quantification of three cardiac biomarkers on a single test (T) line for early diagnosis of acute myocardial infarction (AMI). Owing to the signal amplification of encoded SERS nanotags and high surface area to vol. ratio (SVR) of nitrocellulose (NC) membrane, rapid quantification of CK-MB, cTnI, and Myo with ultra-high sensitivity and wide linear dynamic range (LDR) was realized. We envision this method to find wide applications in in vitro diagnostics (IVD).
- 756Liu, X.; Yang, X.; Zhao, Z.; Li, X.; Liang, J.; Sun, Y.; Xiao, R.; Wang, G. Four-in-One” multifunctional nanohybrids integrated magnetic colorimetric catalytic SERS-driven lateral flow immunoassay for ultrasensitive detection of MPXV. Chemical Engineering Journal 2024, 499, 155995, DOI: 10.1016/j.cej.2024.155995Google ScholarThere is no corresponding record for this reference.
- 757Zheng, P.; Wu, L.; Raj, P.; Kim, J. H.; Paidi, S. K.; Semancik, S.; Barman, I. Multiplexed SERS Detection of Serum Cardiac Markers Using Plasmonic Metasurfaces. Advanced Science 2024, 11, 2405910, DOI: 10.1002/advs.202405910Google ScholarThere is no corresponding record for this reference.
- 758Zhang, Z.; Wu, Y.; Cao, X.; Gao, J.; Yan, S.; Su, S.; Wu, Y.; Zhou, N.; Wang, X.; Chen, L. Highly Monodisperse Stable Gold Nanorod Powder for Optical Sensor. Nano Lett. 2024, 24, 15127– 15135, DOI: 10.1021/acs.nanolett.4c04640Google ScholarThere is no corresponding record for this reference.
- 759Zhong, D.; Chen, W.; Xia, Z.; Hu, R.; Qi, Y.; Zhou, B.; Li, W.; He, J.; Wang, Z.; Zhao, Z.; Ding, D.; Tian, M.; Tang, B. Z.; Zhou, M. Aggregation-induced emission luminogens for image-guided surgery in non-human primates. Nat. Commun. 2021, 12, 6485, DOI: 10.1038/s41467-021-26417-2Google Scholar759Aggregation-induced emission luminogens for image-guided surgery in non-human primatesZhong, Danni; Chen, Weiyu; Xia, Zhiming; Hu, Rong; Qi, Yuchen; Zhou, Bo; Li, Wanlin; He, Jian; Wang, Zhiming; Zhao, Zujin; Ding, Dan; Tian, Mei; Tang, Ben Zhong; Zhou, MinNature Communications (2021), 12 (1), 6485CODEN: NCAOBW; ISSN:2041-1723. (Nature Research)During the past two decades, aggregation-induced emission luminogens (AIEgens) have been intensively exploited for biol. and biomedical applications. Although a series of investigations have been performed in non-primate animal models, there is few pilot studies in non-human primate animal models, strongly hindering the clin. translation of AIE luminogens (AIEgens). Herein, we present a systemic and multifaceted demonstration of an optical imaging-guided surgical operation via AIEgens from small animals (e.g., mice and rabbits) to rhesus macaque, the typical non-human primate animal model. Specifically, the folic conjugated-AIE luminogen (folic-AIEgen) generates strong and stable fluorescence for the detection and surgical excision of sentinel lymph nodes (SLNs). Moreover, with the superior tumor/normal tissue ratio and rapid tumor accumulation, folic-AIEgen successfully images and guides the precise resection of invisible cancerous metastases. Taken together, the presented strategies of folic-AIEgen based fluorescence intraoperative imaging and visualization-guided surgery show potential for clin. applications.
- 760Gao, S.; Zhang, Y.; Cui, K.; Zhang, S.; Qiu, Y.; Liao, Y.; Wang, H.; Yu, S.; Ma, L.; Chen, H.; Ji, M.; Fang, X.; Lu, W.; Xiao, Z. Self-stacked small molecules for ultrasensitive, substrate-free Raman imaging in vivo. Nat. Biotechnol. 2024, 1– 12, DOI: 10.1038/s41587-024-02342-9Google ScholarThere is no corresponding record for this reference.
- 761Kang, J. W.; Park, Y. S.; Chang, H.; Lee, W.; Singh, S. P.; Choi, W.; Galindo, L. H.; Dasari, R. R.; Nam, S. H.; Park, J.; So, P. T. C. Direct observation of glucose fingerprint using in vivo Raman spectroscopy. Science Advances 2020, 6, eaay5206, DOI: 10.1126/sciadv.aay5206Google ScholarThere is no corresponding record for this reference.
- 762Ou, Z.; Duh, Y.-S.; Rommelfanger, N. J.; Keck, C. H. C.; Jiang, S.; Brinson, K.; Zhao, S.; Schmidt, E. L.; Wu, X.; Yang, F.; Cai, B.; Cui, H.; Qi, W.; Wu, S.; Tantry, A.; Roth, R.; Ding, J.; Chen, X.; Kaltschmidt, J. A.; Brongersma, M. L.; Hong, G. Achieving optical transparency in live animals with absorbing molecules. Science 2024, 385, eadm6869, DOI: 10.1126/science.adm6869Google ScholarThere is no corresponding record for this reference.
- 763Liu, L.; Chu, H.; Yang, J.; Sun, Y.; Ma, P.; Song, D. Construction of a magnetic-fluorescent-plasmonic nanosensor for the determination of MMP-2 activity based on SERS-fluorescence dual-mode signals. Biosens. Bioelectron. 2022, 212, 114389, DOI: 10.1016/j.bios.2022.114389Google Scholar763Construction of a magnetic-fluorescent-plasmonic nanosensor for the determination of MMP-2 activity based on SERS-fluorescence dual-mode signalsLiu, Lin; Chu, Hongyu; Yang, Jukun; Sun, Ying; Ma, Pinyi; Song, DaqianBiosensors & Bioelectronics (2022), 212 (), 114389CODEN: BBIOE4; ISSN:0956-5663. (Elsevier B.V.)Matrix metalloproteinase 2 (MMP-2) is a crucial biomarker of tumor growth, invasion and metastasis. In the present study, a core-satellite magnetic-fluorescent-plasmonic nanosensor (FMNS@Au) was constructed through biol. self-assembly to generate localized SERS "hot spots" and an efficient FRET system for the sensitive detn. of MMP-2 activity in a SERS-fluorescence dual-mode assay. In this hybrid nanosensor, a biotin-labeled peptide contg. a specific MMP-2 substrate (PLGVR) was employed as a bridge for the assembly of gold nanoparticles (AuNPs) and avidin functionalized fluorescent-magnetic nanospheres (FMNS). The modified RB on FMNS served as a Raman reporter and a donor of FRET, while the AuNPs assembled on FMNS acted as SERS substrates and acceptors of FRET. In the presence of MMP-2, the SERS "hot spot" effect was weakened and the FRET system was disrupted through enzymic cleavage of PLGVR, resulting in a redn. of SERS signal and the recovery of fluorescence emission. Importantly, this combination of SERS and fluorescence assay methods in the dual-mode nanosensor broadened the detection range for MMP-2 to 1-200 ng mL-1, with a limit of detection of 0.35 ng mL-1 and a limit of quantitation of 1.17 ng mL-1. In addn., our novel nanosensor affords semi-quant. sensing of MMP-2 by naked-eye observation and accurate detection of MMP-2 through dual-mode anal. The practicality of FMNS@Au was validated by detn. of MMP-2 activity in cell secretions and human serum samples. The designed FMNS@Au nanosensor holds great potential for clin. diagnosis of protease-related diseases.
- 764Bi, X.; Lin, L.; Chen, Z.; Ye, J. Artificial Intelligence for Surface-Enhanced Raman Spectroscopy. Small Methods 2024, 8, e2301243, DOI: 10.1002/smtd.202301243Google ScholarThere is no corresponding record for this reference.
- 765Kumar, P. P. P.; Kaushal, S.; Lim, D.-K. Recent advances in nano/microfabricated substrate platforms and artificial intelligence for practical surface-enhanced Raman scattering-based bioanalysis. TrAC Trends in Analytical Chemistry 2023, 168, 117341, DOI: 10.1016/j.trac.2023.117341Google ScholarThere is no corresponding record for this reference.
- 766Mahmoud, A. Y.F.; Teixeira, A.; Aranda, M.; Relvas, M. S.; Quintero, S.; Sousa-Silva, M.; Chicharo, A.; Chen, M.; Hashemi, M.; King, J. B.; Tunnell, J. W.; Morasso, C.; Piccotti, F.; Corsi, F.; Henriksen-Lacey, M.; de Aberasturi, D. J.; Mendez-Merino, D.; Rodriguez-Paton, A.; Abalde-Cela, S.; Dieguez, L. Will data analytics revolution finally bring SERS to the clinic?. TrAC Trends in Analytical Chemistry 2023, 169, 117311, DOI: 10.1016/j.trac.2023.117311Google ScholarThere is no corresponding record for this reference.
- 767Yang, Y.; Chen, X.; Ai, B.; Zhao, Y. The impact of analyte size on SERS enhancement location, enhancement factor, excitation wavelength, and spectrum. Sensors & Diagnostics 2024, 3, 668– 676, DOI: 10.1039/D4SD00014EGoogle ScholarThere is no corresponding record for this reference.
- 768Bell, S. E.; McCourt, M. R. SERS enhancement by aggregated Au colloids: effect of particle size. Phys. Chem. Chem. Phys. 2009, 11, 7455– 7462, DOI: 10.1039/b906049aGoogle Scholar768SERS enhancement by aggregated Au colloids: effect of particle sizeBell, Steven E. J.; McCourt, Maighread R.Physical Chemistry Chemical Physics (2009), 11 (34), 7455-7462CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)Aggregated Au colloids were widely used as SERS enhancing media for many years but to date there was no systematic study of the effect of the particle size on the enhancements given by simple aggregated Au colloid solns. Previous systematic studies on isolated particles in soln. or multiple particles deposited onto surfaces reported widely different optimum particle sizes for the same excitation wavelength and also disagreed on the extent to which surface plasmon absorption spectra were a good predictor of enhancement factors. The spectroscopic properties of a range of samples of monodisperse Au colloids with diams. ranging from 21 to 146 nm were studied in soln. The UV/visible absorption spectra of the colloids show complex changes as a function of aggregating salt (MgSO4) concn. which diminish when the colloid is fully aggregated. Under these conditions, the relative SERS enhancements provided by the variously sized colloids vary very significantly across the size range. The largest signals in the raw data are obsd. for 46 nm colloids but correction for the total surface area available to generate enhancement shows that particles with 74 nm diam. give the largest enhancement per unit surface area. The obsd. enhancements do not correlate with absorbance at the excitation wavelength but the large differences between differently sized colloids demonstrate that even in the randomly aggregated particle assemblies studied here, inhomogeneous broadening does not mask the underlying changes due to differences in particle diam.
- 769Le Ru, E.; Meyer, M.; Blackie, E.; Etchegoin, P. Advanced aspects of electromagnetic SERS enhancement factors at a hot spot. Journal of Raman Spectroscopy: An International Journal for Original Work in all Aspects of Raman Spectroscopy, Including Higher Order Processes, and also Brillouin and Rayleigh Scattering 2008, 39, 1127– 1134, DOI: 10.1002/jrs.1945Google ScholarThere is no corresponding record for this reference.
- 770Pan, L.; Zhang, P.; Daengngam, C.; Peng, S.; Chongcheawchamnan, M. A review of artificial intelligence methods combined with Raman spectroscopy to identify the composition of substances. J. Raman Spectrosc. 2022, 53, 6– 19, DOI: 10.1002/jrs.6225Google Scholar770A review of artificial intelligence methods combined with Raman spectroscopy to identify the composition of substancesPan, Liangrui; Zhang, Peng; Daengngam, Chalongrat; Peng, Shaoliang; Chongcheawchamnan, MitchaiJournal of Raman Spectroscopy (2022), 53 (1), 6-19CODEN: JRSPAF; ISSN:0377-0486. (John Wiley & Sons Ltd.)A review. In general, most of the substances in nature exist in mixts., and the noninvasive identification of mixt. compn. with high speed and accuracy remains a difficult task. However, the development of Raman spectroscopy, machine learning, and deep learning techniques has paved the way for achieving efficient anal. tools capable of identifying mixt. components, thus leading to an apparent breakthrough in the identification of mixts. beyond traditional chem. anal. methods. This review summarizes the work of Raman spectroscopy in identifying the compn. of substances; reviews the preprocessing process of Raman spectroscopy, artificial intelligence anal. methods, and anal. procedures; and examines the application of artificial intelligence. Finally, the advantages and disadvantages and development prospects of Raman spectroscopy are discussed in detail.
- 771He, Q.; Tong, T.; Habib, F.; Yu, C. Machine learning-assisted surface-enhanced Raman spectroscopic characterization of biological systems. In Machine Learning and Artificial Intelligence in Chemical and Biological Sensing; Elsevier: 2024; pp 147– 175.Google ScholarThere is no corresponding record for this reference.
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Abstract
Figure 1
Figure 1. Schematic illustration of the direct and indirect adsorption.
Figure 2
Figure 2. Examples of solution-phase NP-based application. (a) Digital SERS analysis of paraquat in lake water and thiram in bean sprouts extract by using chloride-capped Ag NPs as the enhancing substrates. Reproduced from ref (16). Copyright 2024, The Authors, under exclusive license to Springer Nature Limited. (b) SERS spectra of CV, doxorubicin (DOX), niraparib (NI) obtained on pristine (i), hedroxyethyl-cellulose stabilized (ii), and PVP-capped Au nanostars. Reproduced from ref (17). Copyright 2021, The Authors. (c) SERS spectra of negatively charged dye labeled DNA using Ag NPs modified by spermine (blue), spermidine (red), and ethylenedioxy-diethylamine (black) as the enhancing substrates, respectively. Reproduced from ref (18). Copyright 2012, Royal Society of Chemistry. (d) SERS spectra of MDMA detected by Ag NPs modified with different feedstock proportion of mixed thiols, as well as the normal Raman spectrum of MDMA pow der. Reproduced from ref (19). Copyright 2012, Royal Society of Chemistry. (e) SERS analysis of methanol by using CB modified Au NPs as the enhancing substrates. Reproduced from ref (20). Copyright 2017, Royal Society of Chemistry.
Figure 3
Figure 3. Methods and application of self-assembled NPs. (a–d) Schematic illustrations of the different methods for overcoming interparticle electrostatic repulsion in interfacial NP self-assembly. Panels a–d were adapted with permission from ref (46). Copyright 2021, The Royal Society of Chemistry. (e) Schematic illustrations of interfacial plasmonic arrays used as the enhancing substrate for SERS detection of norepinephrine in rat brain microdialysates. Reproduced with permission from ref (67). Copyright 2022, Wiley-VCH-GmbH. (f) Schematic illustration of in situ biphasic SERS performed using interfacial arrays as the enhancing substrate. (g) SERS spectra of (i) Au interfacial arrays, (ii–iii) Au interfacial arrays containing 10–3 and 10–5 M naphthalene introduced from the oil phase, (iv–vii) Au interfacial array containing 10–5 M naphthalene introduced from water, hexane, or chloroform phase of the interfacial array, respectively. Panels f–g were adapted with permission fromref (21). Copyright 2022, The Authors. (h) Examples of plasmonic interfacial arrays deposited on various supporting materials. The scalebars corresponds to 0.5 cm. Adapted with permissions from ref (68). Copyright 2021, The Authors. (I) Schematic illustration and photograph showing bacterial headspace probed in situ via SERS using interfacial arrays deposited on quartz as the enhancing substrate. Headspace SERS spectra of the time dependent adsorption from broth spiked with 10–2 M dimethyl disulfide. Adapted with permissions from ref (69). Copyright 2028, Wiley-VCH-GmbH.
Figure 4
Figure 4. Dynamic SERS method. (a) Dark-field optical microscopy for real-time tracing of the morphological alterations of a specific aggregate in the evaporation process of a 1 mL sample. This sample of Ag sols was 10-fold diluted with 0.01 mM citrate solution to avoid overly strong light scattering. Reproduce from ref (88). Long-period and high-stability 3D hotspots for the detection of different molecules. SERS spectra obtained at different concentrations of (b1) NOD and (c1) TBZ in 5% glycerol system. Time-dependent Raman spectra of (b2) NOD and (c2) TBZ based on the long period and high-stability 3D hotspot matrix constructed with the assistance of 5% glycerol. (88,89) A liquid-phase SERS method. (d) Reversible O/W encasing for self-assembly of metal liquid-like Au nanorod arrays is realized in a common cuvette. (e) SERS spectra of TBZ with concentrations of 1, 101, 102, 103, and 104 ppm, respectively. (f) A linear plot of r780/662 against logarithmic concentration of pesticide. Reproduce from ref (14). Capillary capturing target molecules into small gaps method. Schematic diagram of the assembled NP film (g1–i1) and high-speed camera picture (g2–i2) from the initial wet stage to final dry stage of the monolayer NP film. (j) SERS spectra collected from a single A549 cell during the cell death process caused by photothermal stimulation. (k) Schematic diagram of the capillary SERS method for in situ monitoring of the single-cell death process under photothermal stimulation. Reproduced from ref (93).
Figure 5
Figure 5. Scheme of enrichment process of dye molecules. (a) Schematic of the multianalyte and multiphase enrichment using the acoustic levitating platform and the consequent multiplex and multiphase SERS detection. (b) Enrichment process of dye molecules from 10 μL of ethanol solutions. Reproduced from ref (90). Copyright 2022, The Authors.
Figure 6
Figure 6. Raman imaging of SERS hydrogels. (a) 2D imaging of the SERS intensity at 1083 cm–1 in hydrogels with different Au nanorod concentrations: (i) 0.1 mM, (ii) 0.5 mM, (iii) 1 mM, and (iv) 1.5 mM, respectively. Adapted with permission from ref (105). Copyright 2020, John Wiley and Sons. (b) Comparison between the CFM imaging and high-spatial-resolution SERS imaging of the hydrogel scaffold supporting SERS nanotag-labeled tumoroids. Adapted with permission from ref (106). Copyright 2024, The Authors.
Figure 7
Figure 7. Fabrication of MOFs. (a) TEM images of Au spherical particles coated with a homogeneous silica shell. Of 98.5 ± 7.0 nm. Adapted with permission from ref (119). Copyright 2009, American Chemical Society. (b) TEM images of a single Au nanostar mesoporous silica coated yolk shell. Adapted with permission from ref (122). Copyright 2019, Royal Society of Chemistry. (c) SEM and TEM/XED analysis of mesoporous silica shells containing Au island films in their interior. Adapted with permission from ref (123). Copyright 2019, John Wiley and Sons. (d) SEM image of core–shell Au nanostars coated with MOF (ZIF-8). Adapted with permission from ref (133). Copyright 2019, John Wiley and Sons. (e) TEM image of yolk shell Au nanostars coated with MOF (ZIF-8) after dissolution of the inner ZIF-67. Adapted with permission from ref (128). Copyright 2023, John Wiley and Sons. (f) STEM images (bright and dark field) for PS@Ag, Ag@ZIF-thin, and thick plasmonic-MOFs. Adapted with permission from ref (135). Copyright 2024, John Wiley and Sons.
Figure 8
Figure 8. Applications of SERS MOFs. (a) (i) SERS spectra of different concentrations of bathocuproine adsorbed on PS@Ag@ZIF-8. (ii) SERS spectrum of the sediments obtained after several washing cycles. (iii) Comparison between the SERS intensities of bathocuproine (band at 1377 cm–1) on PS@Ag@ZIF-8 and PS@Ag after the same washing samples. (iv) SERS spectra of bathocuproine on PS@Ag@ZIF-8 upon immersion into Cu(II) solutions in PBS buffer at different copper concentrations (from 38 to 254 ppb). Adapted with permission from ref (134). Copyright 2023, American Chemical Society. (b) (i) SERS spectral kinetics acquired on a nanostar coated with MOF and loaded with a nucleus dye (Hoechst 33258, HOE) with and without NIR illumination (785 nm); solid and dashed lines represent the time points 0 and 8 h, respectively. Kinetics was built with the SERS intensity of the ring breathing mode of HOE (980 cm–1). (ii) White light image (top) and SERS images of a single cell with the MOF composite time 0 (middle) and after 8 h of irradiation (down). (iii) Confocal microscopy image of cells incubated with core–shell containing HOE before and after NIR treatment. Blue and orange colors represent HOE and cell membrane staining (CellMask Deep Red), respectively. Adapted with permission from ref (133). Copyright 2019, John Wiley and Sons. (c) Photocatalytical degradation curves of rhodamine B under green illumination. Intensity corresponds to band 1202 cm–1. SERS spectra are presented as a 3D graph to guide the diminishing of the intensity across the full spectrum. Adapted with permission from ref (135). Copyright 2024, John Wiley and Sons.
Figure 9
Figure 9. ZnO superstructures and related optical properties. (a) Diagram that illustrates the microstructure of a ZnO superstructure comprised of closely packed nanocrystallites. (b) The comparison of enhancement factor and near-field scattering efficiency observed on ZnO superstructures with different diameters under the 532 nm excitation. Inset shows the corresponding SEM and electric-field distribution images of ZnO superstructures. (c) Potential CT transition pathway and vibronic coupling mechanism. Adapted with permission from ref (168). Copyright 2019, Wiley-VCH Verlag.
Figure 10
Figure 10. Typical fabrication process of SERS nanotags: noble metal NPs, Raman reporter molecule adsorption, protective layer coating, and modification layer attachment.
Figure 11
Figure 11. Characterization and formation mechanism of GERTs. (a) Geometrical illustration of a GERT. (b) The molecular structures, (c) TEM images, and (d) SERS spectra of GERTs with different organic molecules embedded. Reproduced from ref (194). Copyright 2020, The Authors. (e) GERTs with interior gaps of different thickness. Reproduced from ref (211). Copyright 2018, American Chemical Society. (f) Growth mechanism illustration using molecular dynamics simulation. Reproduced from ref (212). Copyright 2021, American Chemical Society. (g) Different core morphologies of GERTs. (i) Petal-like shell GERTs. Reproduced from ref (203). Copyright 2019, The Authors. (ii) Au bipyramid GERTs. Reproduced from ref (214). Copyright 2024, The Authors. (iii) Au nanotriangle GERTs. Reproduced from ref (215). Copyright 2019, American Chemical Society. (iv) Dual-gap nanodumbbell GERTs. Reproduced from ref (216). Copyright 2023, Wiley. (v) Multishell nanorod GERTs. Reproduced from ref (217). Copyright 2016, Elsevier. (vi) Au petal-like core with Ag shell GERTs. Reproduced from ref (218). Copyright 2023, The Authors.
Figure 12
Figure 12. Design and application of orthogonal Raman molecules. (a) Three-color SERS imaging of HeLa cells using SERS nanotags of an alkyne SERS palette; the SERS nanotags were modified with OPE0 (red), OPE1 (green), and OPE2 (blue). Reproduced from ref (239). (b) (i) “Click” SERS for 10-plex synchronous biomarkers detection. Reproduce from ref (240). (ii) “Mixing” SERS for multiplex detection of liver cancer antigens. Reproduce from ref (241). (iii) “Combined” SERS emissions for high-throughput optical labels on microscale objects, such as bacterium. Reproduce from ref (242).
Figure 13
Figure 13. Representative NIR-II SERS nanotags. (a) Quantitative enhancement factor study of NIR-II resonant nanorods. Reproduced from ref (257). Copy 2022, American Chemical Society. (b) Design and optical properties of Au@Au–Ag dot-in-cubic nanoframes. They show high SERS intensity to penetrate thick phantoms. Reproduced from ref (261). Copyright 2021, Wiley. (c) NIR-II SERS nanotags made with pc-AuAg NSs and its application for in vivo SERS imaging of tumors. (i) Schematic illustration of the synthetic process of pc-AuAg NSs. (ii) SEM image of Ag and Au of pc-AuAg NSs. (iii) Schematic illustration of the application of NIR-II SERS nanotags for in vivo imaging of tumors in a 4T1 tumor-bearing mouse. Reproduced from ref (262). Copyright 2022, The Authors. (d) The core–shell nanotags with IR-1064 molecules embedded. (i) Schematic illustration of the synthetic process of the core–shell nanotags. (ii) Absorbance spectra of IR-1064 molecules and core–shell nanotags. (iii) They were applied for sentinel lymph node (SLN) detection. Reproduced from ref (263). Copyright 2024, Elsevier.
Figure 14
Figure 14. RBCm coated SERS NPs. (a) Schematic diagram showing preparation of RBCm vesicles and successful coating on anisotropic Au NPs, leading to RBCM-coated AuNP-RBCm with enhanced dispersibility and biofunctionalization properties. Physicochemical characterization of anisotropic RBCM-coated AuNPs. Negative-stained transmission electron micrographs of (b) bare AuNP1, (c) RBCm-coated AuNP1, (e) bare AuNP2, (f) RBCm-coated AuNP2, (h) bare AuNP3, and (i) RBCm-coated AuNP3. The membrane coating in (c, f, i) are highlighted with white lines. (d, g, j) UV–vis absorbance spectra of AuNPs and AuNP-RBCMs, with the inset boxes zoomed. The inset shows the intrinsic plasmonic absorbance peak shift for different anisotropic AuNPs upon RBCM coating. Reproduced from ref (280). Copyright 2022, American Chemical Society.
Figure 15
Figure 15. Illustration of optical tweezers-coupled SERS platforms. (a) SERS-active satellite transport by laser tweezers to the surface of a cell. (b) Raman tweezing. (c) Autoenhanced Raman spectroscopy and time-dependent Raman signals after laser exposure. (d) Optical tweezers-coupled Raman spectroscopic platform. SERS spectra and intensity as a function of the distance between two Ag NP-coated beads from beads approaching to beads separating. (e) Optical plasmonic tweezer-coupled SERS platform. SERS spectra recorded at a Ag NP-coated bead dimer with the switching of trapping laser between on (red) and off (black) states. Adapted with permission from refs (284−288). Copyrights 2015, Royal Society of Chemistry; 2011, American Chemical Society; 2016, American Chemical Society; 2021, The Author(s); and 2023, The Authors, respectively.
Figure 16
Figure 16. Plasmonic nanopores and related applications. (a) Plasmonic nanopore-based single molecule electrical and optical measurement. Reproduced from ref (309). (b) Integrated system for the optical and electrical detection of nanopore analysis. Reproduced from ref (309). (c) In situ electrochemical modification of metallic nanopore. Reproduced from ref (309). (d) Schematic of a solid-state nanopore with an integrated bowtie-antenna structure for DNA translocation experiments. Reproduced from refs (310and311). (e) Schematic of the bowl-shaped plasmonic nanopore system for Raman detection of single DNA molecules. Reproduced from ref (316). (f) Schematic diagram for the dynamic SM-SERS detection by plasmonic nanopipettes. Reproduced from refs (318and319).
Figure 17
Figure 17. Plasmonic nanopore for biomolecule sequencing. (a) Unfolding a protein for plasmonic nanopore sequencing. (b) The schematic of the plasmonic bowl-shaped nanopore system in which the DNA (green line) would be first uncoiled by the hydrogel (blue circles) and then passed through the hot spot. (c) The cross-sectional distribution of the surface charge of the bowl-shaped nanopore under electric bias. (d) The simulated EO flow distribution in the bowl-shaped nanopore and path of the DNA movement under electric bias (white line). (e) Schematic of the particle-in-pore sensor that could trap single Au NP for tens of seconds. (f) The molecule would be adsorbed on the NP before trapping. (g) The generated gap-mode hot spot with size of 1–3 amino acids. (h) The time series of collected single-molecule SERS spectra of the vasopressin peptide in the electro-plasmonic nanopore. (i, j, k) Single-molecule SERS spectra at different times from (h) that represent the neighboring amino acids. Panels (b–d) are adapted with permission from ref (316). Copyright 2023, American Chemical Society, and panels (e–k) are adapted with permission from ref (283). Copyright 2022, American Chemical Society.
Figure 18
Figure 18. Wearable SERS-based sensing devices. SEM images of (a) Ag nanomushroom array, (b) Au nanosphere cone array, (c) Au-coated electrospun thermoplastic polyurethane fibers, and (d) Au nanomesh. (e) TEM image of Ag nanocube superlattice. Scale bar: 50 nm. SEM images of (f) plasmonic nanovoids array (scale bars: 1 μm (top) and 200 nm (bottom)), (g) Au nanorods on chromatography paper, and (h) Au nanospheres on alkalized V2C MXene membrane. Inset: optical image of the Au NP-modified MXene membrane. (i) Optical image of a SERS sensor within PDMS microfluidics and (j) corresponding continuous SERS measurements of lactate with varying concentrations. (k) Optical image of SERS sensors distributed along a paper microfluidic channel and (l) continuous SERS measurements of uric acid with varying concentrations. (m) Optical image of a portable Raman spectrometer used in on-body measurements. (n) Optical image of a multiplex sensor array with a sweat extraction system. Scale bar: 1 cm. (a, i, j) Reproduced from ref (341). Open access. (b) Reproduced with permission from ref (335). Copyright ACS. (c) Reproduced with permission from ref (339). Copyright ACS. (d) Reproduced from ref (340). (e, n) Reproduced from ref (337). Open access. (f) Reproduced with permission from ref (342). Copyright Wiley. (g, k, l, m) Reproduced from ref (336). Open access. (h) Reproduced with permission from ref (345). Copyright ACS.
Figure 19
Figure 19. Widefield and holography Raman imaging. (a) Schematic widefield microscope extended with “beam homogenization” and “imaging and spectroscopy” modules. The beam homogenization module ensures a flat illumination profile over the entire field of observation to allow quantitative SERS intensity measurements. The imaging and spectroscopy unit simultaneously records an image of the sample plane alongside a spectrally dispersed copy of said image on the same sCMOS camera. This combination ultimately allows extracting single-particle spectra from the camera recordings. Adapted with permission from ref (369). Copyright 2022, John Wiley and Sons. (b) Optical image and single shot SERS imaging of large plasmonic surfaces of 3 mm × 3 mm and the corresponding and SERS spectra taken along the blue lines marked. The bold spectrum represents the mean spectrum. Adapted with permission from ref (368). Copyright 2022, American Chemical Society. (c) Schematic of the spectrally resolved holographic widefield microscope composed of a Michelson and a shearing interferometer enabling simultaneously spectrally resolved imaging and image-phase measurements. The sample is widefield illuminated and the red-shifted SERS signal separated from residual laser light with a dichroic beamsplitter and a long-pass filter. After propagating through a Michelson interferometer, a conjugate image is formed that is relay-imaged onto an sCMOS camera. A 2D 0-π phase grating is placed slightly offset with respect to the conjugate image plane and generates multiple diffraction orders which propagate through the relay imaging system. A hard aperture placed into the Fourier plane isolates the four first diffraction orders which ultimately self-interfere on the camera. The insets highlight the grating-induced change in PSF (left vs right) alongside a schematic of the Fourier filter. (d) Live cell SERS particle tracking. The SERS signal (pink), recorded at a fluence of 1.8 kW/cm2 and an integration time of 250 ms, is superimposed onto a brightfield image, recorded using Koehler illumination with a 470 nm fiber-coupled LED, of the cells. The trajectories of individual SERS particles are color-coded to show the respective z-positions which are obtained by 3D localizing the particles from image stacks generated via numerical propagation. 40 time-points are recorded per minute. (c, d) Adapted with permission from ref (371). Copyright 2020, Springer-Nature.
Figure 20
Figure 20. Conventional SERS frequency analysis strategies. (a) Summary of conventional steps for SERS frequency analysis. (b) Schematic illustration of spectral preprocessing strategies. (c) Peak identification and deconvolution to unravel the reaction events at Ag-MP@ZIF by deconvolution of SERS spectra from 1280 to 1400 cm–1. Reprinted and adapted with permission from (c) ref (385). Copyright 2020, American Chemical Society.
Figure 21
Figure 21. Standardization and calibration of SERS frequency shift among samples. (a) (i) Scheme illustration of external standard calibration method and (ii) calibration for R6G ranging from 10–7 to 10–16 M using 610 cm–1 intensity. (b) (i) Scheme illustration of internal standard calibration method and (ii) calibration for Cu2+ quantification showing SERS spectra and ratio (I2223/I1378) as Cu2+ concentration ranging from 0 to 18 mM. (c) (i) Scheme illustration of standard addition method and calibration of nitroxoline in urine and SERS spectra upon spiking different concentration of nitroxoline. Reprinted and adapted with permission from (a) ref (406), (b) ref (408), and (b) ref (412). Copyrights 2013, 2016, 2021, American Chemical Society.
Figure 22
Figure 22. Unsupervised machine learning for SERS frequency shift analysis. (a) 3D PCA score plot of the ternary mixture (FE: 0.1 μg/mL, HER: 10 μg/mL, KET: 10 μg/mL) and its single components and the corresponding LLI SERS spectra. (b) UMAP plot showing an overlaid density contour plot and pixels reordered in correct spatial correlation and colored by clusters identified in UMAP. (c) Hierarchical clustering analysis of measured MPY SERS, which categorizes the bacteria species on three main levels using ECM surface chemotype-based classification factors, namely, surface charge, overall ECM chemical characteristics, and type and number of interacting functional groups. Reprinted and adapted with permission from (a) ref (424), (b) ref (429), and (c) ref (432). Copyright 2023, American Chemical Society.
Figure 23
Figure 23. Supervised machine learning for SERS frequency shift analysis. (a) PLS regression plot of measured against actual mol % L-TRP. The calibration curve is constructed from spectra collected in varying mol % L-TRP mixtures at 10 mM total [TRP] and comparison of measured vs actual mol % L-TRP in different test samples using the NPGB/EC-SERS platform. (b) Support vector machine classification for differentiation between SERS spectra collected from healthy control and prenatal disease. (c) Confusion matrix of averaged classification outcomes across 100 model iterations using a random forest (RF) classifier. The F1 scores are indicated in brackets. Reprinted and adapted with permission from (a) ref (434), (b) ref (437), and (c) ref (432). Copyrights 2018, 2021, 2023, American Chemical Society.
Figure 24
Figure 24. Enhancing machine learning model interpretability. (a) Feature importance scores extracted from SHAP analysis for classification among SERS spectra of with high, medium, and low concentration of biomarker 2,3-DHBA. (b) Correlation between PCA score plot and PCA loading plot unravel the spectral changes induced by different types of interactions from different probe molecules. (c) Density function theory (DFT) simulation reveal ring complexation between APDS and SO2 to confirm the identified SERS spectral changes. Reprinted and adapted with permission from (a) ref (457), (b) ref (425), and (c) ref (426). Copyright 2021, American Chemical Society. Copyright 2024, Elsevier. Copyright 2022, Wiley.
Figure 25
Figure 25. Development of denoising strategies in Raman spectrum (1D) and Raman imaging (3D), from conventional signal processing algorithms to supervised and self-supervised deep learning ones. For spectral denoising: (a) PEER, a signal processing algorithm integrating peak extraction and retention, (470) (b) a supervised algorithm based on instrumental noise learning, (471) and (c) P2P, a zero-shot self-supervised spectral denoising algorithm. (472) For Raman imaging denoising: (d) a signal processing algorithm integrating Fourier transform denoising with imaging moving average filter, (473) (e) a two-stage supervised algorithm integrating both spectral and imaging processing, (474) and (f) S2S, a zero-shot self-supervised hyperspectral imaging denoising algorithm. (475)
Figure 26
Figure 26. Emerging techniques for SERS quantification. (a) Different factors causing SERS intensity fluctuations including different electromagnetic enhancement due to variable distance between the analyte and the substrate surface (i, ii) and variable adsorption site (i, iii), different adsorption orientations (iv), atomic mobilization (v), NP aggregation (vi), and heterogeneous substrate morphology (vii). (b) Signal calibration by the internal standard. The signal intensity of the analytes can be interfered by a lot of uncontrollable factors while the ratio of analyte signal to internal standard signal can correct these variations, realizing more robust quantification. Three typical strategies of internal standards: (c) co-adsorption of the internal standard molecules with the analytes on the SERS substrate and (d) embedment of the internal standard molecules in the core–shell NP and sensing of the analytes on the outer layer via direct adsorption, specific capturing or analyte-induced chemical change of the surface functionalized molecules. (e) Intrinsic internal standards originated from the substrate and the solvent. (f) The concept of digital colloid-enhanced Raman spectroscopy by single-molecule counting. (g) Dual-mode SERS and electrochemical detection of miRNA. Adapted from ref (523).
Figure 27
Figure 27. Multiplex SERS detection of nucleic acids. (a) An LFA-SERS sensor combined with CHA for multiplex detection of miRNAs on a single test line. Adapted from ref (575). (b) Magnetic pull-down of target miRNAs for multiplex SERS labeling, forming core–satellite complexes in the presence of target miRNAs. Adapted from ref (576). (c) Identification of nucleic acid targets using acetylene-tagged Hoechst molecules binding to DNA-tethered Au NPs. Adatped from ref (578). (d) Locker probes-assisted RPA combined with proximity-programmed SERS nanotags for the detection of fusion genes. Adapted from ref (582).
Figure 28
Figure 28. Prediction and modeling of protein molecular species. (a) Three different fields involved in SERS: Raman spectroscopy, nanosurface science, and nanoplasmonics. The most representative examples for modeling nanoplasmonics (left) and nanosurface science (right) in the very beginning are illustrated. (601,610). (b) Models for protein in different environment: powder, solution, adsorbed protein, and free protein in the hotspots. Adapted from ref (602). (c) MD simulation can be used for screening orientations of peptides or proteins. (d) Quantum and classical electrodynamics indicate the distance-dependent phenomenon for SERS. (e) SERS trajectory in Euler space can be described as different orientations in the hotspots. (f) Schematic diagram of SPARC for calculating SERS spectra of proteins. Adapted from ref (626).
Figure 29
Figure 29. SERS immunoassays for liquid biopsy-based protein marker detection. (a) The Au NP array functionalized with IL-6 aptamers for detecting IL-6 through changes in the aptamer’s SERS signal. Adapted from ref (630). (b) A digital single-molecule nanopillar SERS platform for parallel counting of four types of cytokines. Adapted from ref (631). (c) A plasmonic internal standard-embedded LFA-SERS platform for the duplex detection of protein markers. Adapted from ref (636). (d) A multiplex, pump-free SERS microfluidic chip for the duplex detection of protein biomarkers across multiple samples. Adapted from ref (638).
Figure 30
Figure 30. SERS analysis of metabolites. (a) SERS analysis of the conversion of tryptophan (Trp) into Kynurenine (Kyn), catalyzed by the IDO-1 enzyme. Reproduced from ref (643). Copyright 2020, John Wiley and Sons. (b) Evaluation of cell death mechanisms by application of SERS and machine learning. Reproduced from ref (646). Copyright 2024, The Authors.
Figure 31
Figure 31. SERSome for robust metabolic profiling. (a) The concept of SERSome and the comparison with single spectra and averaged spectra for the detection of complex molecular systems. Reproduced from ref (652). (b) Convolutional neural network for SERSome analysis and SERS-based disease diagnosis. Reproduced from ref (648). (c) SERSome-based biomarker screening and the subsequent biological validation of the biomarker candidates. Reproduced from ref (650).
Figure 32
Figure 32. Overview of strategies for selective small metabolites sensing.
Figure 33
Figure 33. Analyte manipulation and capturing strategy for selective small metabolite sensing. (a) Schematic illustration of the use of charge and geometry complementarity/mismatch to direct the probe–analogue coupling toward the chondroitin sulfates’ isomerism sites and induce multidentate interactions for formation of analogue-specific complex geometries when 4-mercaptopyridine (MPY) is selected as the multidentate probe, yielding differentiable SERS spectra as evidenced by distinct clusters on PCA score plot. (b) Detection of mycotoxins using SERS competitive immunoassays. (c) SERS-based sensor chip consisting of multiple SERS nanotags for accurate COVID-19 detection. (d) Mechanism of selective physical confinement using MOF, in which molecules with diameter larger than the pore aperture (2-naphthaldehyde) is separated , whereas 4-ethylbenzaldehyde can diffuse into the MOF, thus provide accurate quantification of 4-ethylbenzaldehyde. Reprinted and adapted with permission from (a) ref (662), (b) ref (666), (c) ref (435), and (d) ref (675). Copyright 2018, 2023 Wiley. Copyright 2022, American Chemical Society.
Figure 34
Figure 34. Multimodal techniques for selective small metabolites sensing. (a) Multimodal technique using SERS and photoacoustic for accurate in vivo quantification of H2O2. (b) Hyphenated technique using electrochemical-SERS (EC-SERS) to manipulate the analyte (d- and l-tryptophan) orientation and adsorption onto the Au nanoporous bowl (NPGB), showing superiority of EC-SERS, as evidenced by distinct clusters on the PCA score plot, in contrast to the conventional SERS (no Vapplied) which results in overlapping clusters. Reprinted and adapted with permission from (a) ref (677) and (b) ref (434). Copyright 2021, Wiley. Copyright 2021, American Chemical Society.
Figure 35
Figure 35. Workflow of microfluidic droplet-SERS platform for single-cell encapsulation and simultaneous detection of three metabolites produced by a single cell. Reproduce with permission from ref (685).
Figure 36
Figure 36. SERS imaging and endoscopic imaging of tumors. (a) Photograph and distribution of SERS nanotags related with s420-CA9, s421-IgG4, and s440-CD47 in bladder tumor. (b) Stem plot to illustrate tumor and normal tissue. (c) Binding of s421-IgG4 in normal and tumor tissue samples. Reproduced with permission from ref (711). (d) The estimation of the pH value employing a SERS-based endoscope equipped with a pH sensitive Raman reporter molecule in HeLa cells treated with cisplatin. (e) Variation of fluorescence intensity in HeLa cells treated with cisplatin and (f) the related fluorescence images. The incubation time with cisplatin was 0, 1, 3, 9, and 24 h. The scale bar in (f) represents 20 μm. Reproduced with permission from ref (713).
Figure 37
Figure 37. Concepts and applications of deep Raman spectroscopy. (a) SESORS concept: SERS signal is recovered noninvasively using SORS concept in which the illumination and collection zones are spatially separated from each other on sample surface. SETRS concept: The configuration separates the excitation laser and the Raman detector on opposite sides of the sample to collect the SERS signals. (b) SETRS detections through 7.1 cm-thick biological tissues. Reproduced from ref (743). (c) SETRS detections through 14 cm thick ex vivo porcine tissues. Reproduced from ref (226). (d) The home-built TRS system with ultrabright SERS nanotags, a fiber-optic Raman probe, a 785 nm laser with a diffuse beam. Adapted from ref (226). (e) Scheme of ratiometric Raman spectroscopy to calculate the depth of SERS in biological tissues. (f) Noninvasive in vivo detection and localization of 6.5 mm deep SLNs in rats using ratiometric TRS. Adapted from ref (747). (g) Tomographic TRS enables the rapid three-dimensional localization of SERS nanotags in thick tissues. Adapted from ref (749). (h) Raman spectral projection tomography system to the imaging and visualization of Raman molecules in phantoms. Reproduced from ref (750).
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- 3Ervin, K. M.; Koglin, E.; Sequaris, J. M.; Valenta, P.; Nürnberg, H. W. Surface enhanced Raman spectra of nucleic acid components adsorbed at a silver electrode. Journal of Electroanalytical Chemistry and Interfacial Electrochemistry 1980, 114, 179– 194, DOI: 10.1016/S0022-0728(80)80446-33Surface enhanced Raman spectra of nucleic acid components adsorbed at a silver electrodeErvin, K. M.; Koglin, E.; Sequaris, J. M.; Valenta, P.; Nuernberg, H. W.Journal of Electroanalytical Chemistry and Interfacial Electrochemistry (1980), 114 (2), 179-94CODEN: JEIEBC; ISSN:0022-0728.High-resoln. vibrational spectra of nucleic acid components adsorbed on Ag electrode were obtained using a spectroelectrochem. method based on the large-intensity enhancement for Raman scattering at electrode surfaces. The laser surface Raman spectra of purine, adenine, adenosine, deoxyadenosine, adenine mononucleotides, adenylyl-3',5'-adenosine and polyriboadenylic acid were recorded in the range of 150-3500 cm-1. The intensities of the vibrational bands were highly dependent upon the electrochem. prepn. of the electrode, the applied potential and the nature of the adsorbate species. High-intensity spectra in rather dil. bulk solns. were obtained. The phosphate derivs. of adenosine exhibited strongly enhanced Raman scattering. Spectral band frequencies corresponded closely with normal Raman spectra of these mols. in soln. The adenine ring breathing mode at 740 cm-1 and the adenine ring skeletal vibration at 1335 cm-1 produced prominent Raman scattering. A strong band at about 240 cm-1 for the adenine mononucleotides was attributed to Ag/adsorbed phosphate group vibrations.
- 4Koglin, E.; Séquaris, J. M.; Valenta, P. Surface enhanced raman spectroscopy of nucleic acid bases on Ag electrodes. J. Mol. Struct. 1982, 79, 185– 189, DOI: 10.1016/0022-2860(82)85050-3There is no corresponding record for this reference.
- 5Cotton, T. M.; Schultz, S. G.; Van Duyne, R. P. Surface-enhanced resonance Raman scattering from cytochrome c and myoglobin adsorbed on a silver electrode. J. Am. Chem. Soc. 1980, 102, 7960– 7962, DOI: 10.1021/ja00547a0365Surface-enhanced resonance Raman scattering from cytochrome c and myoglobin adsorbed on a silver electrodeCotton, Therese M.; Schultz, Steven G.; Van Duyne, Richard P.Journal of the American Chemical Society (1980), 102 (27), 7960-2CODEN: JACSAT; ISSN:0002-7863.Surface enhanced resonance Raman spectra are reported for cytochrome c and myoglobin spontaneously adsorbed from micromolar solns. onto a Ag electrode. The enhancement factor is estd. to be ∼105 above that produced by the conventional resonance Raman effect. The signal intensities in both proteins are anodization and potential dependent. All resonance Raman bands are depolarized (ρ ≥0.5) on the electrode. These observations are consistent with an enhancement mechanism similar to that underlying the surface enhanced Raman (SER) effect in small mols. adsorbed on Ag electrodes. Both cytochrome and myoglobin undergo potential dependent redox changes at the electrode. These results clearly indicate the great potential of combined SER and resonance Raman spectroscopy for bioanal. applications such as the study of: (1) rare, difficult to isolate, or highly dil. prepns. and (2) redox active biomols. adsorbed on electrodes.
- 6Cotton, T. M.; Kim, J.-H.; Chumanov, G. D. Application of surface-enhanced Raman spectroscopy to biological systems. J. Raman Spectrosc. 1991, 22, 729– 742, DOI: 10.1002/jrs.1250221203There is no corresponding record for this reference.
- 7Ozaki, Y. Medical Application of Raman Spectroscopy. Appl. Spectrosc. Rev. 1988, 24, 259– 312, DOI: 10.1080/05704928808060459There is no corresponding record for this reference.
- 8Nie, S.; Emory, S. R. Probing Single Molecules and Single Nanoparticles by Surface-Enhanced Raman Scattering. Science 1997, 275, 1102– 1106, DOI: 10.1126/science.275.5303.11028Probing single molecules and single nanoparticles by surface-enhanced Raman scatteringNie, Shuming; Emory, Steven R.Science (Washington, D. C.) (1997), 275 (5303), 1102-1106CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)Optical detection and spectroscopy of single mols. and single nanoparticles were achieved at room temp. using surface-enhanced Raman scattering. Individual Ag colloidal nanoparticles were screened from a large heterogeneous population for special size-dependent properties and were then used to amplify the speculation for special size-dependent properties and were then used to amplify the spectroscopic signatures of adsorbed mols. For single rhodamine 6G mols. adsorbed on the selected nanoparticles, the intrinsic Raman enhancement factors were ∼1014 to 1015, much larger than the ensemble-averaged values derived from conventional measurements. This enormous enhancement leads to vibrational Raman signals that are more intense and more stable than single-mol. fluorescence.
- 9Kneipp, K.; Wang, Y.; Kneipp, H.; Perelman, L. T.; Itzkan, I.; Dasari, R. R.; Feld, M. S. Single Molecule Detection Using Surface-Enhanced Raman Scattering (SERS). Phys. Rev. Lett. 1997, 78, 1667– 1670, DOI: 10.1103/PhysRevLett.78.16679Single molecule detection using surface-enhanced Raman scattering (SERS)Kneipp, Katrin; Wang, Yang; Kneipp, Harald; Perelman, Lev T.; Itzkan, Irving; Dasari, Ramachandra R.; Feld, Michael S.Physical Review Letters (1997), 78 (9), 1667-1670CODEN: PRLTAO; ISSN:0031-9007. (American Physical Society)By exploiting the extremely large effective cross sections (10-17-10-16 cm2/mol.) available from surface-enhanced Raman scattering (SERS), the authors achieved the 1st observation of single mol. Raman scattering. Measured spectra of a single crystal violet mol. in aq. colloidal Ag soln. using one 2nd collection time and ∼2 × 105 W/cm2 nonresonant near-IR excitation show a clear fingerprint of its Raman features between 700 and 1700 cm-1. Spectra obsd. in a time sequence for an av. of 0.6 dye mol. in the probed vol. exhibited the expected Poisson distribution for actually measuring 0, 1, 2, or 3 mols.
- 10Qian, X.; Peng, X.-H.; Ansari, D. O.; Yin-Goen, Q.; Chen, G. Z.; Shin, D. M.; Yang, L.; Young, A. N.; Wang, M. D.; Nie, S. In vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tags. Nat. Biotechnol. 2008, 26, 83– 90, DOI: 10.1038/nbt137710In vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tagsQian, Ximei; Peng, Xiang-Hong; Ansari, Dominic O.; Yin-Goen, Qiqin; Chen, Georgia Z.; Shin, Dong M.; Yang, Lily; Young, Andrew N.; Wang, May D.; Nie, ShumingNature Biotechnology (2008), 26 (1), 83-90CODEN: NABIF9; ISSN:1087-0156. (Nature Publishing Group)The authors describe biocompatible and nontoxic nanoparticles for in vivo tumor targeting and detection based on pegylated gold nanoparticles and surface-enhanced Raman scattering (SERS). Colloidal gold has been safely used to treat rheumatoid arthritis for 50 years, and has recently been found to amplify the efficiency of Raman scattering by 14-15 orders of magnitude. Here the authors show that large optical enhancements can be achieved under in vivo conditions for tumor detection in live animals. An important finding is that small-mol. Raman reporters such as org. dyes were not displaced but were stabilized by thiol-modified polyethylene glycols. These pegylated SERS nanoparticles were considerably brighter than semiconductor quantum dots with light emission in the near-IR window. When conjugated to tumor-targeting ligands such as single-chain variable fragment (ScFv) antibodies, the conjugated nanoparticles were able to target tumor biomarkers such as epidermal growth factor receptors on human cancer cells and in xenograft tumor models.
- 11Doctor, E. L.; McCord, B. Comparison of aggregating agents for the surface-enhanced Raman analysis of benzodiazepines. Analyst 2013, 138, 5926– 5932, DOI: 10.1039/c3an00669gThere is no corresponding record for this reference.
- 12Sahu, B. K.; Dwivedi, A.; Pal, K. K.; Pandian, R.; Dhara, S.; Das, A. Optimized Au NRs for efficient SERS and SERRS performances with molecular and longitudinal surface plasmon resonance. Appl. Surf. Sci. 2021, 537, 147615, DOI: 10.1016/j.apsusc.2020.14761512Optimized Au NRs for efficient SERS and SERRS performances with molecular and longitudinal surface plasmon resonanceSahu, Binaya Kumar; Dwivedi, Aradhana; Pal, Kuntal Kumar; Pandian, R.; Dhara, S.; Das, A.Applied Surface Science (2021), 537 (), 147615CODEN: ASUSEE; ISSN:0169-4332. (Elsevier B.V.)Chem. stable and biocompatible gold nanorods (Au NRs) are an excellent building block for plasmonic-based applications, including surface-enhanced Raman spectroscopy (SERS). However, the quest for controlling the aspect ratio (AR) for desirable application needs an in-depth understanding of the synthesis procedure. In this article, the seed-mediated growth of Au NRs with a controlled AR is reported. Influencing reagents, including the seed concn., are varied individually to unfurl the impact of them on AR. A subsequent optimized protocol is developed to achieve a fine-tuning in the longitudinal surface plasmonic resonance (LSPR) of Au NRs with a narrow distribution of NRs and minimal byproducts. The effect of resonance of LSPR peaks closely tallying both 785 and 532 nm with laser excitations are studied for SERS applications using rhodamine 6G (R6G) dye. Furthermore, the mol. resonance of R6G analyte is achieved successfully with a 532 nm excitation laser to accomplish as high of 10-12 M, thanks to the suitable ARs and the surface-enhanced resonance Raman scatterings (SERRS) phenomenon. The enhancement factor is calcd. to be 5 x 109, which allows Raman intensity mapping for a trace amt. of R6G, demonstrating the potential utility of Au NRs for applications.
- 13Valera, P. S.; Plou, J.; Garcia, I.; Astobiza, I.; Viera, C.; Aransay, A. M.; Martin, J. E.; Sasselli, I. R.; Carracedo, A.; Liz-Marzan, L. M. SERS analysis of cancer cell-secreted purines reveals a unique paracrine crosstalk in MTAP-deficient tumors. Proc. Natl. Acad. Sci. U. S. A. 2023, 120, e2311674120, DOI: 10.1073/pnas.2311674120There is no corresponding record for this reference.
- 14Tian, L.; Su, M.; Yu, F.; Xu, Y.; Li, X.; Li, L.; Liu, H.; Tan, W. Liquid-state quantitative SERS analyzer on self-ordered metal liquid-like plasmonic arrays. Nat. Commun. 2018, 9, 3642, DOI: 10.1038/s41467-018-05920-z14Liquid-state quantitative SERS analyzer on self-ordered metal liquid-like plasmonic arraysTian Li; Su Mengke; Yu Fanfan; Xu Yue; Li Lei; Liu Honglin; Xu Yue; Liu Honglin; Tan Weihong; Li Xiaoyun; Tan WeihongNature communications (2018), 9 (1), 3642 ISSN:.Liquid interfacial plasmonic platform is emerging for new sensors, catalysis, and tunable optical devices, but also promises an alternative for practical applications of surface-enhanced Raman spectroscopy (SERS). Here we show that vigorous mixing of chloroform with citrate-capped gold nanorod sols triggers the rapid self-assembly of three-dimensional plasmonic arrays at the chloroform/water (O/W) interface and produces a self-healing metal liquid-like brilliant golden droplet. The O phase itself generates stable SERS fingerprints and is a good homogeneous internal standard for quantitative analysis. This platform presents reversible O/W encasing in a common cuvette determined just by surface wettability of the container. Both O-in-W and W-in-O platforms exhibit excellent SERS sensitivity and reproducibility for different analytes by the use of a portable Raman device. It paves the way toward a practical and quantitative liquid-state SERS analyzer, likened to a simple UV-Vis spectrometer, that is far superior to typical solid substrate-based or nanoparticle sol-based analysis.
- 15Ansar, S. M.; Ameer, F. S.; Hu, W.; Zou, S.; Pittman, C. U., Jr; Zhang, D. Removal of molecular adsorbates on gold nanoparticles using sodium borohydride in water. Nano Lett. 2013, 13, 1226– 9, DOI: 10.1021/nl304703w15Removal of Molecular Adsorbates on Gold Nanoparticles Using Sodium Borohydride in WaterAnsar, Siyam M.; Ameer, Fathima S.; Hu, Wenfang; Zou, Shengli; Pittman, Charles U.; Zhang, DongmaoNano Letters (2013), 13 (3), 1226-1229CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)The mechanism of sodium borohydride removal of organothiols from gold nanoparticles (AuNPs) was studied using an exptl. investigation and computational modeling. Organothiols and other AuNP surface adsorbates such as thiophene, adenine, rhodamine, small anions (Br- and I-), and a polymer (PVP, poly(N-vinylpyrrolidone)) can all be rapidly and completely removed from the AuNP surfaces. A computational study showed that hydride derived from sodium borohydride has a higher binding affinity to AuNPs than organothiols. Thus, it can displace organothiols and all the other adsorbates tested from AuNPs. Sodium borohydride may be used as a hazard-free, general-purpose detergent that should find utility in a variety of AuNP applications including catalysis, biosensing, surface enhanced Raman spectroscopy, and AuNP recycle and reuse.
- 16Bi, X.; Czajkowsky, D. M.; Shao, Z.; Ye, J. Digital colloid-enhanced Raman spectroscopy by single-molecule counting. Nature 2024, 628, 771– 775, DOI: 10.1038/s41586-024-07218-1There is no corresponding record for this reference.
- 17Ye, Z.; Li, C.; Celentano, M.; Lindley, M.; O’Reilly, T.; Greer, A. J.; Huang, Y.; Hardacre, C.; Haigh, S. J.; Xu, Y.; Bell, S. E. J. Surfactant-free Synthesis of Spiky Hollow Ag–Au Nanostars with Chemically Exposed Surfaces for Enhanced Catalysis and Single-Particle SERS. JACS Au 2022, 2, 178– 187, DOI: 10.1021/jacsau.1c0046217Surfactant-free Synthesis of Spiky Hollow Ag-Au Nanostars with Chemically Exposed Surfaces for Enhanced Catalysis and Single-Particle SERSYe, Ziwei; Li, Chunchun; Celentano, Maurizio; Lindley, Matthew; O'Reilly, Tamsin; Greer, Adam J.; Huang, Yiming; Hardacre, Christopher; Haigh, Sarah J.; Xu, Yikai; Bell, Steven E. J.JACS Au (2022), 2 (1), 178-187CODEN: JAAUCR; ISSN:2691-3704. (American Chemical Society)Spiky/hollow metal nanoparticles have applications across a broad range of fields. However, the current bottom-up methods for producing spiky/hollow metal nanoparticles rely heavily on the use of strongly adsorbing surfactant mols., which is undesirable because these passivate the product particles' surfaces. Here we report a high-yield surfactant-free synthesis of spiky hollow Au-Ag nanostars (SHAANs). Each SHAAN is composed of >50 spikes attached to a hollow ca. 150 nm diam. cubic core, which makes SHAANs highly plasmonically and catalytically active. Moreover, the surfaces of SHAANs are chem. exposed, which gives them significantly enhanced functionality compared with their surfactant-capped counterparts, as demonstrated in surface-enhanced Raman spectroscopy (SERS) and catalysis. The chem. accessibility of the pristine SHAANs also allows the use of hydroxyethyl cellulose as a weakly bound stabilizing agent. This produces colloidal SHAANs that remain stable for >1 mo while retaining the functionalities of the pristine particles and allows even single-particle SERS to be realized.
- 18van Lierop, D.; Krpetić, Ž.; Guerrini, L.; Larmour, I. A.; Dougan, J. A.; Faulds, K.; Graham, D. Positively charged silver nanoparticles and their effect on surface-enhanced Raman scattering of dye-labelled oligonucleotides. Chem. Commun. 2012, 48, 8192– 8194, DOI: 10.1039/c2cc31731a18Positively charged silver nanoparticles and their effect on surface-enhanced Raman scattering of dye-labelled oligonucleotidesvan Lierop, Danny; Krpetic, Zeljka; Guerrini, Luca; Larmour, Iain A.; Dougan, Jennifer A.; Faulds, Karen; Graham, DuncanChemical Communications (Cambridge, United Kingdom) (2012), 48 (66), 8192-8194CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)Improved pos. charged nanoparticles are described to provide a simplified SERS substrate for DNA detection. Complete flocculation of the nanoparticles is prevented due to the controlled analyte induced aggregation. This provides a stable aggregation state which significantly extends the anal. window simplifying DNA detection by SERS.
- 19Stewart, A.; Bell, S. E. J. Modification of Ag nanoparticles with mixed thiols for improved SERS detection of poorly adsorbing target molecules: detection of MDMA. Chem. Commun. 2011, 47, 4523– 4525, DOI: 10.1039/c0cc05312kThere is no corresponding record for this reference.
- 20de Nijs, B.; Kamp, M.; Szabó, I.; Barrow, S. J.; Benz, F.; Wu, G.; Carnegie, C.; Chikkaraddy, R.; Wang, W.; Deacon, W. M.; Rosta, E.; Baumberg, J. J.; Scherman, O. A. Smart supramolecular sensing with cucurbit[n]urils: probing hydrogen bonding with SERS. Faraday Discuss. 2017, 205, 505– 515, DOI: 10.1039/C7FD00147A20Smart supramolecular sensing with cucurbit[n]urils: probing hydrogen bonding with SERSde Nijs, Bart; Kamp, Marlous; Szabo, Istvan; Barrow, Steven J.; Benz, Felix; Wu, Guanglu; Carnegie, Cloudy; Chikkaraddy, Rohit; Wang, Wenting; Deacon, William M.; Rosta, Edina; Baumberg, Jeremy J.; Scherman, Oren A.Faraday Discussions (2017), 205 (Surface Enhanced Raman Scattering--SERS), 505-515CODEN: FDISE6; ISSN:1359-6640. (Royal Society of Chemistry)Rigid gap nano-aggregates of Au nanoparticles formed using cucurbit[n]uril (CB[n]) mols. are used to investigate the competitive binding of ethanol and methanol in an aq. environment. We show it is possible to detect as little as 0.1% methanol in water and a ten times higher affinity to methanol over ethanol, making this a useful technol. for quality control in alc. prodn. We demonstrate strong interaction effects in the SERS peaks, which we demonstrate are likely from the hydrogen bonding of water complexes in the vicinity of the CB[n]s.
- 21Li, C.; Chen, Z.; Huang, Y.; Zhang, Y.; Li, X.; Ye, Z.; Xu, X.; Bell, S. E. J.; Xu, Y. Uncovering strong π-metal interactions on Ag and Au nanosurfaces under ambient conditions via in-situ surface-enhanced Raman spectroscopy. Chem. 2022, 8, 2514– 2528, DOI: 10.1016/j.chempr.2022.06.00821Uncovering strong π-metal interactions on Ag and Au nanosurfaces under ambient conditions via in-situ surface-enhanced Raman spectroscopyLi, Chunchun; Chen, Zheng; Huang, Yiming; Zhang, Yingrui; Li, Xinyuan; Ye, Ziwei; Xu, Xin; Bell, Steven E. J.; Xu, YikaiChem (2022), 8 (9), 2514-2528CODEN: CHEMVE; ISSN:2451-9294. (Cell Press)The interactions between arom. mols. and metal nanoparticles are ubiquitous in nanotechnol. Currently, π-metal interactions under ambient conditions are well appreciated for VIIIB but not for IB metals. Here, we demonstrate the direct probing of π-metal interactions under ambient conditions with mol. specificity using surface-enhanced Raman spectroscopy (SERS), which reveals that arom. hydrocarbons adsorb strongly from soln. onto the surfaces of Ag and Au nanoparticles, provided there is no surface oxidn. Theor. modeling shows that this adsorption is driven by dispersive π-metal interactions and that the arom. mols. co-adsorb alongside surface ligands that are present initially on the nanosurface. Finding direct evidence for this long-neglected interaction has significant implications for various applications. This is demonstrated with SERS sensing of an arom. drug mol. whose structure would typically suggest it to be weakly adsorbing, and indeed it is not detected on conventional Ag colloids due to surface oxidn., but it is found to adsorb strongly onto Au particles.
- 22Ye, Z.; Li, C.; Xu, Y.; Bell, S. E. J. Exploiting the chemical differences between Ag and Au colloids allows dramatically improved SERS detection of “non-adsorbing” molecules. Analyst 2019, 144, 448– 453, DOI: 10.1039/C8AN01927D22Exploiting the chemical differences between Ag and Au colloids allows dramatically improved SERS detection of "non-adsorbing" moleculesYe, Ziwei; Li, Chunchun; Xu, Yikai; Bell, Steven E. J.Analyst (Cambridge, United Kingdom) (2019), 144 (2), 448-453CODEN: ANALAO; ISSN:0003-2654. (Royal Society of Chemistry)In colloidal SERS only analytes that can spontaneously adsorb onto nanoparticles are detected. Therefore, considerable effort has been placed on modifying the surface properties of colloidal particles, particularly Ag particles, to promote the absorption of "difficult" analytes which do not spontaneously adsorb to as-prepd. nanoparticles. In contrast, much less attention has been paid to the role which the identity of the underlying metal plays in the absorption since it is widely believed that the chem. properties of Ag and Au are very similar. This leads to the assumption that mols. which do not adsorb to Ag, such as hydrocarbons, will also not adsorb to aggregated Au colloids for SERS measurements. Here, we challenge this common perception by showing that SERS detection of "difficult" arom. targets such as naphthalene, trinitrotoluene and 3,4-methylenedioxymethamphetamine which cannot be achieved even at >10-3 M concns. with bare aggregated Ag colloids is possible at ≥10-8 M with unmodified aggregated Au colloids. For naphthalene and 3,4-methylenedioxymethamphetamine the detection limit obtained in this work with bare citrate-capped Au particles exceeds the previous best limit of detection obtained with surface-modified nanoparticles by an order of magnitude.
- 23Bell, S. E. J.; Sirimuthu, N. M. S. Surface-Enhanced Raman Spectroscopy (SERS) for Sub-Micromolar Detection of DNA/RNA Mononucleotides. J. Am. Chem. Soc. 2006, 128, 15580– 15581, DOI: 10.1021/ja066263w23Surface-Enhanced Raman Spectroscopy (SERS) for Sub-Micromolar Detection of DNA/RNA MononucleotidesBell, Steven E. J.; Sirimuthu, Narayana M. S.Journal of the American Chemical Society (2006), 128 (49), 15580-15581CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Surface-enhanced Raman (SER) spectra of all the DNA/RNA mononucleotides have been obtained with high sensitivity using citrate-reduced silver colloids aggregated with MgSO4, rather than the more usual halide ions, which were found to prevent enhancement of these compds. The SERS spectra of adenine, guanine, thymine, cytosine, and uracil were recorded along with their corresponding nucleosides and 5'-deoxynucleotides. For the cytosine series, all three spectra had similar relative band intensities but the spectra of adenine were different from those of adenosine and dAMP, probably due to differences in orientation on the surface. No enhanced bands from the phosphate or sugar groups were obsd. There were general similarities between the SERS spectra of the purine mononucleotides and the pyrimidine mononucleotides, but the spectra were sufficiently different to allow each of them to be distinguished. This method can therefore be used for high sensitivity, label-free identification of mononucleotides.
- 24Xie, L.; Lu, J.; Liu, T.; Chen, G.; Liu, G.; Ren, B.; Tian, Z. Key Role of Direct Adsorption on SERS Sensitivity: Synergistic Effect among Target, Aggregating Agent, and Surface with Au or Ag Colloid as Surface-Enhanced Raman Spectroscopy Substrate. J. Phys. Chem. Lett. 2020, 11, 1022– 1029, DOI: 10.1021/acs.jpclett.9b0372424Key Role of Direct Adsorption on SERS Sensitivity: Synergistic Effect among Target, Aggregating Agent, and Surface with Au or Ag Colloid as Surface-Enhanced Raman Spectroscopy SubstrateXie, Lifang; Lu, Jianglong; Liu, Tao; Chen, Ganyu; Liu, Guokun; Ren, Bin; Tian, ZhongqunJournal of Physical Chemistry Letters (2020), 11 (3), 1022-1029CODEN: JPCLCD; ISSN:1948-7185. (American Chemical Society)It is widely accepted that the sensitivity of surface-enhanced Raman spectroscopy (SERS) is mainly manipulated by the electromagnetic enhancement mechanism (EM). Herein, the direct adsorption of the target on the SERS active surface is vital as well, through the systematic study of the SERS behavior of 3 pos. charged mols. on neg. charged Au or Ag nanoparticles. Facilitated by the synergistic effect among the mol., the surface, and the specific adsorbed halide ions (Cl-, Br-, and I-), high SERS sensitivity for trace target was realized, which was mainly from the directly adsorbed mols. Noteworthy, little contribution from the nondirectly adsorbed mols. was discernible, although the EM enhancement was at the same level for these 2 surface species dwelling within a distance significantly <1 nm from the surface. Further, the related strategy for trace detection sheds light on how to realize sensitive SERS detection of new targets.
- 25Zhou, Z.; Lu, J.; Wang, J.; Zou, Y.; Liu, T.; Zhang, Y.; Liu, G.; Tian, Z. Trace detection of polycyclic aromatic hydrocarbons in environmental waters by SERS. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 2020, 234, 118250, DOI: 10.1016/j.saa.2020.118250There is no corresponding record for this reference.
- 26Simpson, J.; Craig, D.; Faulds, K.; Graham, D. Mixed-monolayer glyconanoparticles for the detection of cholera toxin by surface enhanced Raman spectroscopy. Nanoscale Horizons 2016, 1, 60– 63, DOI: 10.1039/C5NH00036JThere is no corresponding record for this reference.
- 27Gao, J.; Huang, X.; Liu, H.; Zan, F.; Ren, J. Colloidal Stability of Gold Nanoparticles Modified with Thiol Compounds: Bioconjugation and Application in Cancer Cell Imaging. Langmuir 2012, 28, 4464– 4471, DOI: 10.1021/la204289k27Colloidal Stability of Gold Nanoparticles Modified with Thiol Compounds: Bioconjugation and Application in Cancer Cell ImagingGao, Jie; Huang, Xiangyi; Liu, Heng; Zan, Feng; Ren, JicunLangmuir (2012), 28 (9), 4464-4471CODEN: LANGD5; ISSN:0743-7463. (American Chemical Society)Gold nanoparticles (GNPs) are attractive alternative optical probes and good biocompatible materials due to their special phys. and chem. properties. However, GNPs have a tendency to aggregate particularly in the presence of high salts and certain biol. mols. such as nucleic acids and proteins. How to improve the stability of GNPs and their bioconjugates in aq. soln. is a crit. issue in bioapplications. In this study, we first synthesized 17 nm GNPs in aq. soln. and then modified them with six thiol compds., including glutathione, mercaptopropionic acid (MPA), cysteine, cystamine, dihydrolipoic acid, and thiol-ending polyethylene glycol (PEG-SH), via a Au-S bond. We systematically investigated the effects of the thiol ligands, buffer pH, and salt concns. of the solns. on the colloidal stability of GNPs using UV-vis absorption spectroscopy. We found that GNPs modified with PEG-SH were the most stable in aq. soln. compared to other thiol compds. On the basis of the above results, we developed a simple and efficient approach for modification of GNPs using a mixt. of PEG-SH and MPA as ligands. These biligand-modified GNPs were facilely conjugated to antibody using 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide and N-hydroxysulfosuccinimide as linkage reagents. We conjugated GNPs to epidermal growth factor receptor antibodies and successfully used the antibody-GNP conjugates as targeting probes for imaging of cancer cells using the illumination of a dark field. Compared to current methods for modification and conjugation of GNPs, our method described here is simple, has a low cost, and has potential applications in bioassays and cancer diagnostics and studies.
- 28Gu, Y.; Wu, S.; Luo, Z.; Lin, L. L.; Ye, J. Oppositely-charged silver nanoparticles enable selective SERS molecular enhancement through electrostatic interactions. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 2024, 322, 124852, DOI: 10.1016/j.saa.2024.124852There is no corresponding record for this reference.
- 29Milligan, K.; Shand, N. C.; Graham, D.; Faulds, K. Detection of Multiple Nitroaromatic Explosives via Formation of a Janowsky Complex and SERS. Anal. Chem. 2020, 92, 3253– 3261, DOI: 10.1021/acs.analchem.9b0506229Detection of Multiple Nitroaromatic Explosives via Formation of a Janowsky Complex and SERSMilligan, Kirsty; Shand, Neil C.; Graham, Duncan; Faulds, KarenAnalytical Chemistry (Washington, DC, United States) (2020), 92 (4), 3253-3261CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Military-grade explosives such as 2,4,6-trinitroluene (TNT) are still a major worldwide concern in terms of terror threat and environmental impact. The most common methods currently employed for the detection of explosives involve colorimetric tests, which are known to be rapid and portable; however, they often display false positives and lack sensitivity. Other methods used include ion mobility mass spectrometry, gas chromatog.-mass spectrometry (GC-MS), and liq. chromatog.-mass spectrometry (LC-MS), which despite producing more reliable results often require large, expensive instrumentation and specially trained staff. Here we demonstrate an alternative approach that utilizes the formation of a colored Janowsky complex with nitroarom. explosives through reaction of the enolate ion of 3-mercapto-2-butanone. The colored complex is formed rapidly and can then be detected sensitively using surface-enhanced Raman scattering (SERS). We demonstrate that SERS can be used as a quick, sensitive, and selective technique for the detection of 2,4,6-trinitrotoluene (TNT), hexanitrostillbene (HNS), and 2,4,6-trinitrophenylmethylnitramine (tetryl) with a detection limit of 6.81 ng mL-1 achieved for TNT, 17.2 ng mL-1 for tetryl, and 135.1 ng mL-1 for HNS. This method of detection also requires minimal sample prepn., can be done in a soln.-based format, and utilizes the same precursor reagents for complex formation with each of the explosives which can then be identified due to the specificity of the unique SERS response obtained. We demonstrate the ability to simultaneously identify three explosive compds. within a total anal. time of 10 min. This method of detection shows promise for the development of rapid and portable SERS-based assays which can be utilized in the field in order to achieve reliable and quant. detection.
- 30Saha, K.; Agasti, S. S.; Kim, C.; Li, X.; Rotello, V. M. Gold Nanoparticles in Chemical and Biological Sensing. Chem. Rev. 2012, 112, 2739– 2779, DOI: 10.1021/cr200117830Gold nanoparticles in chemical and biological sensingSaha, Krishnendu; Agasti, Sarit S.; Kim, Chaekyu; Li, Xiaoning; Rotello, Vincent M.Chemical Reviews (Washington, DC, United States) (2012), 112 (5), 2739-2779CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review. Topics include synthesis ans surface functionalization; phys. properties; colorimetric and fluorimetric sensing; elec. al and electrochem. sensing; SERS; gold nanoparticles in quartz crystal microbalance-based sensing; application of gold nanoparticles in bio-barcode assays.
- 31Kasera, S.; Biedermann, F.; Baumberg, J. J.; Scherman, O. A.; Mahajan, S. Quantitative SERS Using the Sequestration of Small Molecules Inside Precise Plasmonic Nanoconstructs. Nano Lett. 2012, 12, 5924– 5928, DOI: 10.1021/nl303345z31Quantitative SERS Using the Sequestration of Small Molecules Inside Precise Plasmonic NanoconstructsKasera, Setu; Biedermann, Frank; Baumberg, Jeremy J.; Scherman, Oren A.; Mahajan, SumeetNano Letters (2012), 12 (11), 5924-5928CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)The authors show how the macrocyclic host, cucurbit[8]uril (CB[8]), creates precise subnanometer junctions between gold nanoparticles while its cavity simultaneously traps small mols.; this enables their reproducible surface-enhanced Raman spectroscopy (SERS) detection. Explicit shifts in the SERS frequencies of CB[8] on complexation with guest mols. provides a direct strategy for abs. quantification of a range of mols. down to 10-11 M levels. This provides a new anal. paradigm for quant. SERS of small mols.
- 32Stewart, A.; Murray, S.; Bell, S. E. J. Simple preparation of positively charged silver nanoparticles for detection of anions by surface-enhanced Raman spectroscopy. Analyst 2015, 140, 2988– 2994, DOI: 10.1039/C4AN02305F32Simple preparation of positively charged silver nanoparticles for detection of anions by surface-enhanced Raman spectroscopyStewart, A.; Murray, S.; Bell, S. E. J.Analyst (Cambridge, United Kingdom) (2015), 140 (9), 2988-2994CODEN: ANALAO; ISSN:0003-2654. (Royal Society of Chemistry)Modification of citrate and hydroxylamine reduced Ag colloids with thiocholine bromide, a thiol functionalized quaternary ammonium salt, creates particles where the zeta potential is switched from the normal values of ∼-50 mV to approx. + 50 mV. These colloids are stable but can be aggregated with metal salts in much the same way as the parent colloids. They are excellent SERS substrates for detection of anionic targets since their pos. zeta potentials promote adsorption of neg. charged ions. This is important because the vast majority of published SERS studies involve cationic or neutral targets. Also, the fact that the modifier is a quaternary ammonium ion means that the neg. surface charge is maintained even at alk. pH. The modified colloids can be used to detect compds. which cannot be detected using conventional neg.-charged citrate or hydroxylamine reduced metal nanoparticles, for example the detection limit was 5.0 × 10-5 M for perchlorate and <8.7 × 10-7 M for tetraphenylporphine tetrasulfonic acid (TPPS). More importantly, picric acid (an explosive) and diclofenac (a nonsteroidal antiinflammatory) could also be analyzed quant. at low concns., 2.5 × 10-5 M and 1.9 × 10-5 M, resp. The correct choice of aggregating agent is important for achieving high sensitivity since the anion in the aggregating salt may compete with anionic targets for surface binding sites. Finally, since the modification procedure simply involves reaction of nanoparticles with a small alkyl thiol deriv., it can easily be adapted to other particle morphologies or metals.
- 33Guan, P.-C.; Zhang, H.; Li, Z.-Y.; Xu, S.-S.; Sun, M.; Tian, X.-M.; Ma, Z.; Lin, J.-S.; Gu, M.-M.; Wen, H.; Zhang, F.-L.; Zhang, Y.-J.; Yu, G.-J.; Yang, C.; Wang, Z.-X.; Song, Y.; Li, J.-F. Rapid Point-of-Care Assay by SERS Detection of SARS-CoV-2 Virus and Its Variants. Anal. Chem. 2022, 94, 17795– 17802, DOI: 10.1021/acs.analchem.2c0343733Rapid Point-of-Care Assay by SERS Detection of SARS-CoV-2 Virus and Its VariantsGuan, Peng-Cheng; Zhang, Hong; Li, Zhi-Yong; Xu, Shan-Shan; Sun, Miao; Tian, Xian-Min; Ma, Zhan; Lin, Jia-Sheng; Gu, Man-Man; Wen, Huan; Zhang, Fan-Li; Zhang, Yue-Jiao; Yu, Guang-Jun; Yang, Chaoyong; Wang, Zhan-Xiang; Song, Yanling; Li, Jian-FengAnalytical Chemistry (Washington, DC, United States) (2022), 94 (51), 17795-17802CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Addressing the spread of coronavirus disease 2019 (COVID-19) has highlighted the need for rapid, accurate, and low-cost diagnostic methods that detect specific antigens for SARS-CoV-2 infection. Tests for COVID-19 are based on reverse transcription PCR (RT-PCR), which requires lab. services and is time-consuming. Here, by targeting the SARS-CoV-2 spike protein, we present a point-of-care SERS detection platform that specifically detects SARS-CoV-2 antigen in one step by captureing substrates and detection probes based on aptamer-specific recognition. Using the pseudovirus, without any pretreatment, the SARS-CoV-2 virus and its variants were detected by a handheld Raman spectrometer within 5 min. The limit of detection (LoD) for the pseudovirus was 124 TU μL-1 (18 fM spike protein), with a linear range of 250-10,000 TU μL-1. Moreover, this assay can specifically recognize the SARS-CoV-2 antigen without cross reacting with specific antigens of other coronaviruses or influenza A. Therefore, the platform has great potential for application in rapid point-of-care diagnostic assays for SARS-CoV-2.
- 34Nguyen, M. T. T.; Dang, L. T.; Van Pham, H. Gold nanorods coated by molecularly imprinted polymer for sensitive and specific SERS detection of dyes. Colloid Polym. Sci. 2023, 301, 577– 586, DOI: 10.1007/s00396-023-05097-y34Gold nanorods coated by molecularly imprinted polymer for sensitive and specific SERS detection of dyesNguyen, Mai Tuyet Thi; Dang, Lan Thi; Van Pham, HaiColloid and Polymer Science (2023), 301 (6), 577-586CODEN: CPMSB6; ISSN:0303-402X. (Springer)Although surface-enhanced Raman scattering (SERS) is an advanced anal. technique, the challenge of low specificity in real sample anal. remains. In this study, we synthesized a hybrid structure based on gold nanorods (AuNRs) coated with a molecularly imprinted polymer (MIP) as a SERS substrate. While the AuNRs strongly enhance the Raman signal of the analyte, the MIP layer allows specific trapping of analyte mols. close to the gold surface. A very thin film of polydopamine with exclusive cavities of rhodamine B enabled ultrasensitive detection of rhodamine B with a 120-fold increase compared to non-imprinted sample. The selectivity of our AuNR@MIP substrate for the detection of rhodamine B in a mixt. of different dyes was also clearly improved. Fortunately, the AuNR@MIP substrate exhibited attractive accuracy and sensitivity toward rhodamine B in spiked orange juice samples. This report demonstrates a promising hybrid structure to improve SERS-based sensing of real samples.
- 35Ding, Q.; Wang, J.; Chen, X.; Liu, H.; Li, Q.; Wang, Y.; Yang, S. Quantitative and Sensitive SERS Platform with Analyte Enrichment and Filtration Function. Nano Lett. 2020, 20, 7304– 7312, DOI: 10.1021/acs.nanolett.0c0268335Quantitative and Sensitive SERS Platform with Analyte Enrichment and Filtration FunctionDing, Qianqian; Wang, Jing; Chen, Xueyan; Liu, Hong; Li, Quanjiang; Wang, Yanling; Yang, ShikuanNano Letters (2020), 20 (10), 7304-7312CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)Surface-enhanced Raman scattering (SERS) technique with naturally born analyte identification capability can achieve ultrahigh sensitivity. However, the sensitivity and quantification capability of SERS are assumed to be mutually exclusive. Here, the authors prohibit the formation of the ultrasensitive SERS sites to achieve a high quantification capability through sepg. the gold (Au) nanorods from approaching each other with thick metal org. framework (MOF) shells. The sensitivity decrease caused by the absence of the ultrasensitive SERS sites is compensated by the analyte enrichment function of a slippery surface. The porous MOF shell around the Au nanorod only allows analytes smaller than the pore size to approach the Au nanorods and contribute to the SERS spectrum within the complex sample, greatly enhancing the analyte identification capability. Overall, the authors demonstrated an integrated SERS platform with analyte enrichment and analyte filtration function, realizing sensitive, quant., and size selective analyte identification in complex environments.
- 36Zhang, L.; Liu, F.; Zou, Y.; Hu, X.; Huang, S.; Xu, Y.; Zhang, L.; Dong, Q.; Liu, Z.; Chen, L.; Chen, Z.; Tan, W. Surfactant-Free Interface Suspended Gold Graphitic Surface-Enhanced Raman Spectroscopy Substrate for Simultaneous Multiphase Analysis. Anal. Chem. 2018, 90, 11183– 11187, DOI: 10.1021/acs.analchem.8b0304036Surfactant-Free Interface Suspended Gold Graphitic Surface-Enhanced Raman Spectroscopy Substrate for Simultaneous Multiphase AnalysisZhang, Liang; Liu, Fang; Zou, Yuxiu; Hu, Xiaoxiao; Huang, Siqi; Xu, Yiting; Zhang, Lufeng; Dong, Qian; Liu, Zhangkun; Chen, Long; Chen, Zhuo; Tan, WeihongAnalytical Chemistry (Washington, DC, United States) (2018), 90 (19), 11183-11187CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Simultaneous multiphase detection of multiplex analytes is important, albeit challenging, esp. in pharmaceuticals anal. since drugs with lipid and water soly. were often administered together for synergistic therapy. Surface-enhanced Raman spectroscopy (SERS) is a label-free and sensitive tool for multiplex analytes detection at multiphase interfaces. However, the requirements of inducers or surfactant surface modification of the SERS substrate have restricted extensive applications. Herein, the authors developed a graphene-isolated-Au-nanocrystal based multiphase anal. system. Unexpectedly, the gold graphitic SERS substrate can simply suspend at the interface of the different phase without the involvement of any surfactant. Therefore, the proximity of substrate with analyte mols. remains unaffected. Such suspended substrate not only ensures sensitive SERS detection but also enables the enrichment of analytes from the different phase simultaneously without interference. Moreover, the graphitic shell of the SERS substrate has a unique vibration band located in the Raman biol. silence region which is utilized as the internal std. and improves the SERS quantification accuracy. Efficient ex vivo multiphase enrichment and detection of mimic lipid- and water-sol. drugs injected into mice were demonstrated with such gold graphitic substrate, showing the potential of this simultaneous multiplex pharmacokinetic anal.
- 37Kwon, S.; Oh, M. J.; Lee, S.; Lee, G.; Jung, I.; Oh, M.; Park, S. Au Octahedral Nanosponges: 3D Plasmonic Nanolenses for Near-Field Focusing. J. Am. Chem. Soc. 2023, 145, 27397– 27406, DOI: 10.1021/jacs.3c08315There is no corresponding record for this reference.
- 38Oh, M. J.; Kwon, S.; Lee, S.; Jung, I.; Park, S. Octahedron in a Cubic Nanoframe: Strong Near-Field Focusing and Surface-Enhanced Raman Scattering. ACS Nano 2024, 18, 7656– 7665, DOI: 10.1021/acsnano.4c00734There is no corresponding record for this reference.
- 39Zhao, L.; Wang, Y.; Jin, S.; An, N.; Yan, M.; Zhang, X.; Hong, Z.; Yang, S. Rational Electrochemical Design of Hierarchical Microarchitectures for SERS Sensing Applications. Nat. Synth. 2024, 3, 867– 877, DOI: 10.1038/s44160-024-00553-1There is no corresponding record for this reference.
- 40Xiong, M.; Jin, X.; Ye, J. Strong plasmon coupling in self-assembled superparamagnetic nanoshell chains. Nanoscale 2016, 8, 4991– 4999, DOI: 10.1039/C5NR09101B40Strong plasmon coupling in self-assembled superparamagnetic nanoshell chainsXiong, Min; Jin, Xiulong; Ye, JianNanoscale (2016), 8 (9), 4991-4999CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)Construction of ordered patterns of plasmonic nanoparticles is greatly important for nanophotonics relevant applications. We have reported a facile and low-cost magnetic field induced self-assembly approach to construct plasmonic superparamagnetic nanoshell (SN) chains up to several hundred micrometers in a few seconds in a large area without templates or other assistance processes. Exptl. and theor. investigations of the near- and far-field optical properties indicate that the super- and sub-radiant modes of the SN chains continuously red shift with the increase of SN no. and the Fano resonance emerges in the infinite double- and triple-line SN chains. Strong plasmon coupling effects in the SN chains result in great elec. field enhancements at visible and IR wavelengths, which indicates that these chain structures potentially can be used as a common substrate for both surface enhanced Raman scattering (SERS) and surface-enhanced IR absorption (SEIRA) application. This fabrication method also offers a general strategy alternative to top-down processing that enables the construction of nanostructures for metamaterials, electromagnetic energy transport, and optical waveguide.
- 41Ye, J.; Wen, F.; Sobhani, H.; Lassiter, J. B.; Van Dorpe, P.; Nordlander, P.; Halas, N. J. Plasmonic nanoclusters: near field properties of the Fano resonance interrogated with SERS. Nano Lett. 2012, 12, 1660– 7, DOI: 10.1021/nl300045341Plasmonic Nanoclusters: Near Field Properties of the Fano Resonance Interrogated with SERSYe, Jian; Wen, Fangfang; Sobhani, Heidar; Lassiter, J. Britt; Dorpe, Pol Van; Nordlander, Peter; Halas, Naomi J.Nano Letters (2012), 12 (3), 1660-1667CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)While the far field properties of Fano resonances are well-known, clusters of plasmonic nanoparticles also possess Fano resonances with unique and spatially complex near field properties. Here we examine the near field properties of individual Fano resonant plasmonic clusters using surface-enhanced Raman scattering (SERS) both from mols. distributed randomly on the structure and from dielec. nanoparticles deposited at specific locations within the cluster. Cluster size, geometry, and interparticle spacing all modify the near field properties of the Fano resonance. For mols., the spatially dependent SERS response obtained from near field calcns. correlates well with the relative SERS intensities obsd. for individual clusters and for specific Stokes modes of a para-mercaptoaniline adsorbate. In all cases, the largest SERS enhancement is found when both the excitation and the Stokes shifted wavelengths overlap the Fano resonances. In contrast, for SERS from carbon nanoparticles we find that the dielec. screening introduced by the nanoparticle can drastically redistribute the field enhancement assocd. with the Fano resonance and lead to a significantly modified SERS response compared to what would be anticipated from the bare nanocluster.
- 42Zhao, Y.; Shi, L.; Tian, Y.; Zhang, L. Self-assembly at Liquid-Liquid Interface: A New SERS Substrate for Analytical Sensing†. Chin. J. Chem. 2023, 41, 569– 580, DOI: 10.1002/cjoc.202200508There is no corresponding record for this reference.
- 43Yogev, D.; Efrima, S. Novel silver metal liquidlike films. J. Phys. Chem. 1988, 92, 5754– 5760, DOI: 10.1021/j100331a041There is no corresponding record for this reference.
- 44Gordon, K. C.; McGarvey, J. J.; Taylor, K. P. Enhanced Raman scattering from liquid metal films formed from silver sols. J. Phys. Chem. 1989, 93, 6814– 6817, DOI: 10.1021/j100355a046There is no corresponding record for this reference.
- 45Booth, S. G.; Dryfe, R. A. W. Assembly of Nanoscale Objects at the Liquid/Liquid Interface. J. Phys. Chem. C 2015, 119, 23295– 23309, DOI: 10.1021/acs.jpcc.5b0773345Assembly of Nanoscale Objects at the Liquid/Liquid InterfaceBooth, Samuel G.; Dryfe, Robert A. W.Journal of Physical Chemistry C (2015), 119 (41), 23295-23309CODEN: JPCCCK; ISSN:1932-7447. (American Chemical Society)A review. Self-assembly of various materials, such as metallic nanoparticles, Janus particles, and carbon nanomaterials, at liq.-liq. interface is discussed. Strategies to induce particle assembly include manipulation of surface chem., surface charge, and potential control. Liq./liq. assembly can be exploited to synthesize materials in situ and template preformed structures. The difficulties encountered when attempting to fully understand the structure of assemblies present at the liq./liq. interface and the development of exptl. techniques to elucidate information about the structure, stability, chem. compn., and reactivity of interfacial assemblies, are discussed.
- 46Ye, Z.; Li, C.; Chen, Q.; Xu, Y.; Bell, S. E. J. Self-assembly of colloidal nanoparticles into 2D arrays at water–oil interfaces: rational construction of stable SERS substrates with accessible enhancing surfaces and tailored plasmonic response. Nanoscale 2021, 13, 5937– 5953, DOI: 10.1039/D0NR08803J46Self-assembly of colloidal nanoparticles into 2D arrays at water-oil interfaces: rational construction of stable SERS substrates with accessible enhancing surfaces and tailored plasmonic responseYe, Ziwei; Li, Chunchun; Chen, Qinglu; Xu, Yikai; Bell, Steven E. J.Nanoscale (2021), 13 (12), 5937-5953CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)A review. Self-assembly at water-oil interfaces has been shown to be a cheap, convenient and efficient route to obtain densely packed layers of plasmonic nanoparticles which have small interparticle distances. This creates highly plasmonically active materials that can be used to give strong SERS enhancement and whose structure means that they are well suited to creating the highly stable, reproducible and uniform substrates that are needed to allow routine and accurate quant. SERS measurements. A variety of methods have been developed to induce nanoparticle self-assembly at water-oil interfaces, fine tune the surface chem. and adjust the position of the nanoparticles at the interface but only some of these are compatible with eventual use in SERS, where it is important that target mols. can access the active surface unimpeded. Similarly, it is useful to transform liq. plasmonic arrays into easy-to-handle free-standing solid films but these can only be used as solid SERS substrates if the process leaves the surface nanoparticles exposed. Here, we review the progress made in these research areas and discuss how these developments may lead towards achieving rational construction of tailored SERS substrates for sensitive and quant. SERS anal.
- 47Yang, N.; You, T.; Gao, Y.; Lu, S.; Yin, P. One-Step Preparation Method of Flexible Metafilms on the Water–Oil Interface: Self-Assembly Surface Plasmon Structures for Surface-Enhanced Raman Scattering Detection. Langmuir 2019, 35, 4626– 4633, DOI: 10.1021/acs.langmuir.8b0427147One-Step Preparation Method of Flexible Metafilms on the Water-Oil Interface: Self-Assembly Surface Plasmon Structures for Surface-Enhanced Raman Scattering DetectionYang, Nan; You, Tingting; Gao, Yukun; Lu, Sichen; Yin, PenggangLangmuir (2019), 35 (13), 4626-4633CODEN: LANGD5; ISSN:0743-7463. (American Chemical Society)The present study demonstrated a one-step method for the first time to fabricate self-assembled gold nanoparticle (AuNP) metafilms at the water-toluene interface by adding polystyrene-polyisoprene-polystyrene as the support layer. The thiolated polyethylene glycol and ethanol were used to tune the surface charge d. on the AuNPs, constructing a balanced situation at the water-toluene interface. The flexible (AuNP) metafilm can be easily obtained after evapn. of the toluene phase and further used as a surface-enhanced Raman scattering (SERS) substrate for trace thiram detection. The SERS sensitivity was tested using std. Raman probes such as crystal violet and malachite green, both with the detect concn. reaching 1 × 10-11 M. Moreover, the excellent reproducibility and elastic properties make the metafilm promising in practical detection. Hence, the trace thiram detection on an orange pericarp was inspected with the detection limit of 0.5 ppm (1 × 10-6 M) as well as a favorable linearity relation with a correlation coeff. of 0.979, exactly matching the realistic application requirements.
- 48Lee, Y. H.; Lee, H. K.; Ho, J. Y. C.; Yang, Y.; Ling, X. Y. Assembling substrate-less plasmonic metacrystals at the oil/water interface for multiplex ultratrace analyte detection. Analyst 2016, 141, 5107– 5112, DOI: 10.1039/C6AN01239F48Assembling substrate-less plasmonic metacrystals at the oil/water interface for multiplex ultratrace analyte detectionLee, Yih Hong; Lee, Hiang Kwee; Ho, Jonathan Yong Chew; Yang, Yijie; Ling, Xing YiAnalyst (Cambridge, United Kingdom) (2016), 141 (17), 5107-5112CODEN: ANALAO; ISSN:0003-2654. (Royal Society of Chemistry)Current substrate-less SERS platforms are limited to uncontrolled aggregation of plasmonic nanoparticles or quasi-cryst. arrays of spherical nanoparticles, with no study on how the lattice structures formed by nanoparticle self-assembly affect their detection capabilities. Here, we organize Ag octahedral building blocks into two large-area plasmonic metacrystals at the oil/water interface, and investigate their in situ SERS sensing capabilities. Amphiphilic octahedra assemble into a hcp. metacrystal, while hydrophobic octahedra assemble into an open square metacrystal. The lower packing d. square metacrystal gives rise to much stronger SERS enhancement than the denser packing hexagonal metacrystal, arising from the larger areas of plasmonic hotspots within the square metacrystal at the excitation wavelength. We further demonstrate the ability of the square metacrystal to achieve quant. ultratrace detection of analytes from both the aq. and org. phases. Detection limits are at the nano-molar levels, with anal. enhancement factors reaching 108. In addn., multiplex detection across both phases can be achieved in situ without any loss of signal quantitation.
- 49Zhang, Y.; Ye, Z.; Li, C.; Chen, Q.; Aljuhani, W.; Huang, Y.; Xu, X.; Wu, C.; Bell, S. E. J.; Xu, Y. General approach to surface-accessible plasmonic Pickering emulsions for SERS sensing and interfacial catalysis. Nat. Commun. 2023, 14, 1392, DOI: 10.1038/s41467-023-37001-149General approach to surface-accessible plasmonic Pickering emulsions for SERS sensing and interfacial catalysisZhang, Yingrui; Ye, Ziwei; Li, Chunchun; Chen, Qinglu; Aljuhani, Wafaa; Huang, Yiming; Xu, Xin; Wu, Chunfei; Bell, Steven E. J.; Xu, YikaiNature Communications (2023), 14 (1), 1392CODEN: NCAOBW; ISSN:2041-1723. (Nature Portfolio)Pickering emulsions represent an important class of functional materials with potential applications in sustainability and healthcare. Currently, the synthesis of Pickering emulsions relies heavily on the use of strongly adsorbing mol. modifiers to tune the surface chem. of the nanoparticle constituents. This approach is inconvenient and potentially a dead-end for many applications since the adsorbed modifiers prevent interactions between the functional nanosurface and its surroundings. Here, we demonstrate a general modifier-free approach to construct Pickering emulsions by using a combination of stabilizer particles, which stabilize the emulsion droplet, and a second population of unmodified functional particles that sit alongside the stabilizers at the interface. Freeing Pickering emulsions from chem. modifiers unlocks their potential across a range of applications including plasmonic sensing and interfacial catalysis that have previously been challenging to achieve. More broadly, this strategy provides an approach to the development of surface-accessible nanomaterials with enhanced and/or addnl. properties from a wide range of nano-building blocks including org. nanocrystals, carbonaceous materials, metals and oxides.
- 50Tian, H.; Li, H.; Fang, Y. Binary Thiol-Capped Gold Nanoparticle Monolayer Films for Quantitative Surface-Enhanced Raman Scattering Analysis. ACS Appl. Mater. & Interfaces 2019, 11, 16207– 16213, DOI: 10.1021/acsami.9b02069There is no corresponding record for this reference.
- 51Wang, X.; Liang, Z.; Chi, X.; Zhao, M.; Shi, X.; Ma, Y. The construction and destruction of gold nanoparticle assembly at liquid-liquid interface for Cd2+ sensing. Anal. Chim. Acta 2022, 1234, 340520, DOI: 10.1016/j.aca.2022.340520There is no corresponding record for this reference.
- 52Si, S.; Liang, W.; Sun, Y.; Huang, J.; Ma, W.; Liang, Z.; Bao, Q.; Jiang, L. Facile Fabrication of High-Density Sub-1-nm Gaps from Au Nanoparticle Monolayers as Reproducible SERS Substrates. Adv. Funct. Mater. 2016, 26, 8137– 8145, DOI: 10.1002/adfm.20160233752Facile Fabrication of High-Density Sub-1-nm Gaps from Au Nanoparticle Monolayers as Reproducible SERS SubstratesSi, Shaorong; Liang, Wenkai; Sun, Yinghui; Huang, Jing; Ma, Weiliang; Liang, Zhiqiang; Bao, Qiaoliang; Jiang, LinAdvanced Functional Materials (2016), 26 (44), 8137-8145CODEN: AFMDC6; ISSN:1616-301X. (Wiley-VCH Verlag GmbH & Co. KGaA)A facile and low-cost approach is demonstrated for the fabrication of high-d. sub-1-nm gaps from Au nanoparticle monolayers as reproducible surface-enhanced Raman scattering (SERS) substrates. Au nanoparticles with larger diams. possess lower surface charge; the obtained large-area nanoparticle monolayer generates a high-d. of sub-1-nm gaps. A remarkable SERS performance with a 1011 magnitude for the Raman enhancement is achieved for 120 nm Au nanoparticle monolayers due to the dramatic increase in the electromagnetic field enhancement when the obtained gap is smaller than 0.5 nm. The Au nanoparticle monolayer is transferred onto a stretchable PDMS substrate and the structural stability and reproducibility of the high-d. sub-1-nm gaps in Au monolayer films are illustrated. The resultant Au nanoparticle monolayer substrates with an increasing particle diam. exhibit tunable plasmonic properties, which control the plasmon-enhanced photocatalytic efficiency for the dimerization of p-aminothiophenol. The findings reported here offer a new opportunity for expanding the SERS application.
- 53Liu, J.-W.; Zhang, S.-Y.; Qi, H.; Wen, W.-C.; Yu, S.-H. A General Strategy for Self-Assembly of Nanosized Building Blocks on Liquid/Liquid Interfaces. Small 2012, 8, 2412– 2420, DOI: 10.1002/smll.20120017253A General Strategy for Self-Assembly of Nanosized Building Blocks on Liquid/Liquid InterfacesLiu, Jian-Wei; Zhang, Shao-Yi; Qi, Hao; Wen, Wu-Cheng; Yu, Shu-HongSmall (2012), 8 (15), 2412-2420, S2412/1-S2412/5CODEN: SMALBC; ISSN:1613-6810. (Wiley-VCH Verlag GmbH & Co. KGaA)A family of water/oil interfaces is introduced to provide effective platforms for rapid fabrication of large-area self-assembled nanofilms composed of various nanosized building blocks, including nanoparticles (NPs), nanocubes (NC), nanowires (NWs), and nanosheets, at room temp. As a general interfacial assembly method, NWs and NPs are co-assembled at the liq./liq. interface. The as-prepd. co-assembled Ag NW and Ag NC films show high surface-enhanced Raman spectroscopy (SERS) intensity, the SERS performance being strongly dependent on the no. ratio of the two kinds of nanosized building blocks. The results demonstrate that this interfacial system provides a general method for the assembly of various nanosized building blocks with different shapes and dimensionalities, and thus paves an alternative pathway for further applications of macroscopic assemblies with different functionalities.
- 54Park, Y.-K.; Yoo, S.-H.; Park, S. Assembly of Highly Ordered Nanoparticle Monolayers at a Water/Hexane Interface. Langmuir 2007, 23, 10505– 10510, DOI: 10.1021/la701445a54Assembly of Highly Ordered Nanoparticle Monolayers at a Water/Hexane InterfacePark, Yong-Kyun; Yoo, Sang-Hoon; Park, SunghoLangmuir (2007), 23 (21), 10505-10510CODEN: LANGD5; ISSN:0743-7463. (American Chemical Society)This paper reports a methodol. for prepg. ordering hydrophilic metal nanoparticles into close-packed 2-dimensional arrays at a hexane-water interface with alkanethiol in the hexane layer. The destabilization of metal nanoparticles by the addn. of alc. caused the nanoparticles to adsorb to an interface where the surface of entrapped Au nanoparticle was in situ coated with the long-chain alkanethiols present in a hexane layer. The adsorption of alkanethiol to the nanoparticle surface caused the conversion of the electrostatic repulsive force to a van der Waals interaction, which is a key feature in forming highly ordered close-packed nanoparticle arrays.
- 55Reincke, F.; Hickey, S. G.; Kegel, W. K.; Vanmaekelbergh, D. Spontaneous Assembly of a Monolayer of Charged Gold Nanocrystals at the Water/Oil Interface. Angew. Chem., Int. Ed. 2004, 43, 458– 462, DOI: 10.1002/anie.20035233955Spontaneous assembly of a monolayer of charged gold nanocrystals at the water/oil interfaceReincke, Francois; Hickey, Stephen G.; Kegel, Willem K.; Vanmaekelbergh, DanielAngewandte Chemie, International Edition (2004), 43 (4), 458-462CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)Dense layers of individual, charged nanocrystals are formed at the aq./org. interface upon a slight redn. of the surface charge. The layers are remarkably robust, they creep up the glass. This method should be widely applicable to a broad range of charged colloids and will lead to the prodn. of new materials.
- 56Du, Y.; Wei, W.; Zhang, X.; Li, Y. Tuning Metamaterials Nanostructure of Janus Gold Nanoparticle Film for Surface-Enhanced Raman Scattering. J. Phys. Chem. C 2018, 122, 7997– 8002, DOI: 10.1021/acs.jpcc.8b0067656Tuning Metamaterials Nanostructure of Janus Gold Nanoparticle Film for Surface-Enhanced Raman ScatteringDu, Yixuan; Wei, Wei; Zhang, Xiaowei; Li, YunboJournal of Physical Chemistry C (2018), 122 (14), 7997-8002CODEN: JPCCCK; ISSN:1932-7447. (American Chemical Society)Large-area metamaterial nanostructures of a Janus gold nanoparticle (AuNP) film decorated with thiol-terminated polymers have been fabricated and tuned at an oil/water interface by a facile and innovative process. The results show that AuNPs had been arrayed with ultrasmall gaps between neighboring particles laminated with polymer which is called a Janus film. This film exhibits a sensitive property for surface-enhanced Raman scattering (SERS) for detn. of both hydrophilic methylene blue and hydrophobic thiram. The structure-dependent SERS of the Janus AuNP film has also been confirmed by a finite-difference time domain (FDTD) method.
- 57Li, J.; Wang, Q.; Wang, J.; Li, M.; Zhang, X.; Luan, L.; Li, P.; Xu, W. Quantitative SERS sensor based on self-assembled Au@Ag heterogeneous nanocuboids monolayer with high enhancement factor for practical quantitative detection. Anal. Bioanal. Chem. 2021, 413, 4207– 4215, DOI: 10.1007/s00216-021-03366-9There is no corresponding record for this reference.
- 58Li, L.; Chin, W. S. Rapid Fabrication of a Flexible and Transparent Ag Nanocubes@PDMS Film as a SERS Substrate with High Performance. ACS Appl. Mater. & Interfaces 2020, 12, 37538– 37548, DOI: 10.1021/acsami.0c07178There is no corresponding record for this reference.
- 59Cecchini, M. P.; Turek, V. A.; Paget, J.; Kornyshev, A. A.; Edel, J. B. Self-assembled nanoparticle arrays for multiphase trace analyte detection. Nat. Mater. 2013, 12, 165– 171, DOI: 10.1038/nmat348859Self-assembled nanoparticle arrays for multiphase trace analyte detectionCecchini, Michael P.; Turek, Vladimir A.; Paget, Jack; Kornyshev, Alexei A.; Edel, Joshua B.Nature Materials (2013), 12 (2), 165-171CODEN: NMAACR; ISSN:1476-1122. (Nature Publishing Group)Nanoplasmonic structures designed for trace analyte detection using surface-enhanced Raman spectroscopy typically require sophisticated nanofabrication techniques. An alternative to fabricating such substrates is to rely on self-assembly of nanoparticles into close-packed arrays at liq./liq. or liq./air interfaces. The d. of the arrays can be controlled by modifying the nanoparticle functionality, pH of the soln. and salt concn. Importantly, these arrays are robust, self-healing, reproducible and extremely easy to handle. Here, the authors report on the use of such platforms formed by Au nanoparticles for the detection of multi-analytes from the aq., org. or air phases. The interfacial area of the Au array in the authors' system is ≈25 mm2 and can be made smaller, making this platform ideal for small-vol. samples, low concns. and trace analytes. Importantly, the ease of assembly and rapid detection make this platform ideal for in-the-field sample testing of toxins, explosives, narcotics or other hazardous chems.
- 60Turek, V. A.; Cecchini, M. P.; Paget, J.; Kucernak, A. R.; Kornyshev, A. A.; Edel, J. B. Plasmonic Ruler at the Liquid–Liquid Interface. ACS Nano 2012, 6, 7789– 7799, DOI: 10.1021/nn302941k60Plasmonic Ruler at the Liquid-Liquid InterfaceTurek, Vladimir A.; Cecchini, Michael P.; Paget, Jack; Kucernak, Anthony R.; Kornyshev, Alexei A.; Edel, Joshua B.ACS Nano (2012), 6 (9), 7789-7799CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)We report on a simple, fast, and inexpensive method to study adsorption and desorption of metallic nanoparticles at a liq./liq. interface. These interfaces provide an ideal platform for the formation of two-dimensional monolayers of nanoparticles, as they form spontaneously and are defect-correcting, acting as 2D "nanoparticle traps". Such two-dimensional, self-assembled nanoparticle arrays have a vast range of potential applications in displays, catalysis, plasmonic rulers, optoelectronics, sensors, and detectors. Here, we show that 16 nm diam. gold nanoparticles can be controllably adsorbed to a water/1,2-dichloroethane interface, and that we can control the av. interparticle spacing at the interface over the range 6-35 nm. The particle d. and av. interparticle spacing are exptl. assessed by measuring the optical plasmonic response of the nanoparticles in the bulk and at the interface and by comparing the exptl. data with existing theor. results.
- 61Velleman, L.; Sikdar, D.; Turek, V. A.; Kucernak, A. R.; Roser, S. J.; Kornyshev, A. A.; Edel, J. B. Tuneable 2D self-assembly of plasmonic nanoparticles at liquid|liquid interfaces. Nanoscale 2016, 8, 19229– 19241, DOI: 10.1039/C6NR05081F61Tuneable 2D self-assembly of plasmonic nanoparticles at liquid|liquid interfacesVelleman, Leonora; Sikdar, Debabrata; Turek, Vladimir A.; Kucernak, Anthony R.; Roser, Steve J.; Kornyshev, Alexei A.; Edel, Joshua B.Nanoscale (2016), 8 (46), 19229-19241CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)Understanding the structure and assembly of nanoparticles at liq.|liq. interfaces is paramount to their integration into devices for sensing, catalysis, electronics and optics. However, many difficulties arise when attempting to resolve the structure of such interfacial assemblies. In this article we use a combination of X-ray diffraction and optical reflectance to det. the structural arrangement and plasmon coupling between 12.8 nm diam. gold nanoparticles assembled at a water|1,2-dichloroethane interface. The liq.|liq. interface provides a molecularly flat and defect-correcting platform for nanoparticles to self-assemble. The amt. of nanoparticles assembling at the interface can be controlled via the concn. of electrolyte within either the aq. or org. phase. At higher electrolyte concn. more nanoparticles can settle at the liq.|liq. interface resulting in a decrease in nanoparticle spacing as obsd. from X-ray diffraction expts. The plasmonic coupling between the nanoparticles as they come closer together is obsd. by a red-shift in the optical reflectance spectra. The optical reflectance and the X-ray diffraction data are combined to introduce a new 'plasmon ruler'. This allows extn. of structural information from simple optical spectroscopy techniques, with important implications for understanding the structure of self-assembled nanoparticle films at liq. interfaces.
- 62Li, C.; Xu, Y.; Li, X.; Ye, Z.; Yao, C.; Chen, Q.; Zhang, Y.; Bell, S. E. J. Unexpected Dual Action of Cetyltrimethylammonium Bromide (CTAB) in the Self-Assembly of Colloidal Nanoparticles at Liquid–Liquid Interfaces. Adv. Mater. Interfaces 2020, 7, 2000391, DOI: 10.1002/admi.20200039162Unexpected Dual Action of Cetyltrimethylammonium Bromide (CTAB) in the Self-Assembly of Colloidal Nanoparticles at Liquid-Liquid InterfacesLi, Chunchun; Xu, Yikai; Li, Xinyuan; Ye, Ziwei; Yao, Chaoyi; Chen, Qinglu; Zhang, Yuanfeng; Bell, Steven E. J.Advanced Materials Interfaces (2020), 7 (14), 2000391CODEN: AMIDD2; ISSN:2196-7350. (Wiley-VCH Verlag GmbH & Co. KGaA)Self-assembly of colloidal nanoparticles at water-oil interfaces offers an efficient way to construct multi-dimensional arrays. Self-assembly is generally induced by using adsorbing mol. "modifiers" or co-solvents to remove the nanoparticles' surface charge. Here, it is shown that cetyltrimethylammonium bromide (CTAB), which is commonly used in bulk quantities in colloidal synthesis, can induce self-assembly of neg. charged colloidal nanoparticles at water-oil interfaces, even at sub-micromolar levels but it does this by providing charge screening rather than removing the surface charge. Since this is a phys. effect, CTAB can promote assembly of nanoparticles regardless of their morphol. or material compn. In the specific case of nanoparticles which allow CTAB to adsorb, such as Au, the self-assembly mechanism switches from charge screening to chem. adsorption as the concn. is increased. These both explain previous observations of spontaneous interfacial assembly and open up further possibilities for deliberately constructing functional nanoparticle arrays without the need for addnl. modifiers or co-solvents.
- 63Lin, X.; Fang, G.; Liu, Y.; He, Y.; Wang, L.; Dong, B. Marangoni Effect-Driven Transfer and Compression at Three-Phase Interfaces for Highly Reproducible Nanoparticle Monolayers. J. Phys. Chem. Lett. 2020, 11, 3573– 3581, DOI: 10.1021/acs.jpclett.0c0111663Marangoni Effect-Driven Transfer and Compression at Three-Phase Interfaces for Highly Reproducible Nanoparticle MonolayersLin, Xiang; Fang, Guoqiang; Liu, Yuanlan; He, Yangyang; Wang, Li; Dong, BinJournal of Physical Chemistry Letters (2020), 11 (9), 3573-3581CODEN: JPCLCD; ISSN:1948-7185. (American Chemical Society)Interfacial self-assembly is a powerful technol. for prepg. large scale nanoparticle monolayers, but fabrication of highly repeatable large scale nanoparticle monolayers remains a challenge. Here the authors develop an oil/H2O/oil (O/W/O) 3-phase system based on the Marangoni effect to fabricate highly reproducible nanoparticle monolayers. Nanoparticles could be easily transferred and compressed from the lower O/W interface to the upper O/W interface due to the interfacial tension gradient. The O/W/O system can be constructed using different kinds of org. solvents. Through this approach, good uniformity and reproducibility of the nanoparticle monolayers could be guaranteed even using a wide range of nanoparticle concns. Also, this strategy is generally applicable to various nanoparticles with different sizes, shapes, components, and surface ligands, which offers a facile and general approach to functional nanodevices.
- 64Konrad, M. P.; Doherty, A. P.; Bell, S. E. J. Stable and Uniform SERS Signals from Self-Assembled Two-Dimensional Interfacial Arrays of Optically Coupled Ag Nanoparticles. Anal. Chem. 2013, 85, 6783– 6789, DOI: 10.1021/ac400860764Stable and Uniform SERS Signals from Self-Assembled Two-Dimensional Interfacial Arrays of Optically Coupled Ag NanoparticlesKonrad, Magdalena P.; Doherty, Andrew P.; Bell, Steven E. J.Analytical Chemistry (Washington, DC, United States) (2013), 85 (14), 6783-6789CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Densely packed interfacial nanoparticle films form spontaneously when aq. Ag colloid is shaken with CH2Cl2 in the presence of a "promoter" such as 10-4 mol dm-3 tetrabutylammonium nitrate (TBA+NO3-), which induces rapid self-assembly of the nanoparticles at the liq./liq. interface without adsorbing onto their surfaces. The particles within these reflective, metal-like liq. films (MeLLFs) are optically coupled and give strong SERS enhancement, similar to that obtained for the same colloid aggregated with optimized concn. of metal salt. However, unlike aggregated colloids, their structure means that they do not settle out of soln. so they give SERS spectra that are stable for >20 h and have good uniformity (relative std. deviation in abs. intensity over 1 mm2 array of 25 points was 1.1%). Since the films lie at the aq./org. interface, they are open to adsorption of analytes from either of the phases and can be probed in situ to detect both water- and non-water-sol. analytes. The detection limit for mercaptobenzoic acid (MBA) added to the org. layer was found to be <2 ppb. These materials therefore combine many of the best features of both patterned surfaces and metal colloids for quant. SERS anal.
- 65Xu, Y.; Konrad, M. P.; Lee, W. W. Y.; Ye, Z.; Bell, S. E. J. A Method for Promoting Assembly of Metallic and Nonmetallic Nanoparticles into Interfacial Monolayer Films. Nano Lett. 2016, 16, 5255– 5260, DOI: 10.1021/acs.nanolett.6b0241865A Method for Promoting Assembly of Metallic and Nonmetallic Nanoparticles into Interfacial Monolayer FilmsXu, Yikai; Konrad, Magdalena P.; Lee, Wendy W. Y.; Ye, Ziwei; Bell, Steven E. J.Nano Letters (2016), 16 (8), 5255-5260CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)Two-dimensional metal nanoparticle arrays are normally constructed at liq.-oil interfaces by modifying the surfaces of the constituent nanoparticles so that they self-assemble. Here we present a general and facile new approach for promoting such interfacial assembly without any surface modification. The method use salts that have hydrophobic ions of opposite charge to the nanoparticles, which sit in the oil layer and thus reduce the Coulombic repulsion between the particles in the org. phase, allowing the particles to sit in close proximity to each other at the interface. The advantage of this method is that because it does not require the surface of the particles to be modified it allows nonmetallic particles including TiO2 and SiO2 to be assembled into dense interfacial layers using the same procedure as is used for metallic particles. This opens up a route to a new family of nanostructured functional materials.
- 66Xu, Y.; Zhang, Y.; Li, C.; Ye, Z.; Bell, S. E. J. SERS as a Probe of Surface Chemistry Enabled by Surface-Accessible Plasmonic Nanomaterials. Acc. Chem. Res. 2023, 56, 2072– 2083, DOI: 10.1021/acs.accounts.3c0020766SERS as a Probe of Surface Chemistry Enabled by Surface-Accessible Plasmonic NanomaterialsXu, Yikai; Zhang, Yingrui; Li, Chunchun; Ye, Ziwei; Bell, Steven E. J.Accounts of Chemical Research (2023), 56 (15), 2072-2083CODEN: ACHRE4; ISSN:0001-4842. (American Chemical Society)A review. The efforts in the development of modifier-free synthetic approaches to synthesize surface-accessible, plasmonic nanomaterials for SERS are discussed. The definition of modifiers and surface-accessibility, esp. in the context of surface chem. studies in SERS, is established. As a general rule of thumb, the chem. ligands on surface-accessible nanomaterials should be easily displaceable by a wide range of target mols. relevant to potential applications. Modifier-free approaches for the bottom-up synthesis of colloidal nanoparticles, which are the basic building blocks for nanotechnol. are introduced. Modifier-free interfacial self-assembly approaches developed by the authors' group that allow the creation of multidimensional plasmonic nanoparticle arrays from different types of nanoparticle-building blocks are introduced. These multidimensional arrays can be further combined with different types of functional materials to form surface-accessible multifunctional hybrid plasmonic materials. Applications for surface-accessible nanomaterials as plasmonic substrates for SERS studies of surface chem. are demonstrated. The removal of modifiers led to significantly enhanced properties and the observation of new surface chem. phenomena that had been previously overlooked or misunderstood in the literature. Realizing the current limitations of modifier-based approaches provides new perspectives in manipulating mol.-metal interactions in nanotechnol. and can have significant implications in the design and synthesis of the next generation of nanomaterials.
- 67Shi, L.; Liu, M.; Zhang, L.; Tian, Y. A Liquid Interfacial SERS Platform on a Nanoparticle Array Stabilized by Rigid Probes for the Quantification of Norepinephrine in Rat Brain Microdialysates. Angew. Chem., Int. Ed. 2022, 61, e202117125, DOI: 10.1002/anie.20211712567A Liquid Interfacial SERS Platform on a Nanoparticle Array Stabilized by Rigid Probes for the Quantification of Norepinephrine in Rat Brain MicrodialysatesShi, Lu; Liu, Mengmeng; Zhang, Limin; Tian, YangAngewandte Chemie, International Edition (2022), 61 (21), e202117125CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)For the reliable detn. of trace chems. in the brain, we created a SERS platform based on a functionalized AuNPs array formed at a liq./liq. interface in a uniform fashion over a large substrate area through ternary regulations for real-time quantification of trace norepinephrine (NE). The rigid mol., 4-(thiophen-3-ylethynyl)-benzaldehyde (RP1) was designed and co-assembled at AuNPs with 4-mercaptophenylboronic acid (MPBA) to chem. define NE via dual recognition. Meanwhile, the rigid structure assembly of RP1 and MPBA efficiently fixed the interparticle gap, guaranteeing reproducible SERS anal. Furthermore, the Raman peak of C≃C group in the silent region was taken as a response element to further improve the accuracy. Combined with microdialysis, this SERS platform was developed for in-the-field testing of NE in rat brain microdialyzates following anxiety.
- 68Song, L.; Xu, B. B.; Cheng, Q.; Wang, X.; Luo, X.; Chen, X.; Chen, T.; Huang, Y. J. S. A. Instant interfacial self-assembly for homogeneous nanoparticle monolayer enabled conformal “lift-on” thin film technology. Science Advances 2021, 7, 2852, DOI: 10.1126/sciadv.abk2852There is no corresponding record for this reference.
- 69Cong, T.; Wang, J.; Zhao, Y.; Zhang, D.; Fan, Z.; Pan, L. Tip-to-tip assembly of urchin-like Au nanostar at water-oil interface for surface-enhanced Raman spectroscopy detection. Anal. Chim. Acta 2021, 1154, 338323, DOI: 10.1016/j.aca.2021.33832369Tip-to-tip assembly of urchin-like Au nanostar at water-oil interface for surface-enhanced Raman spectroscopy detectionCong, Tianze; Wang, Jianzhen; Zhao, Yongpeng; Zhang, Dongmei; Fan, Zeng; Pan, LujunAnalytica Chimica Acta (2021), 1154 (), 338323CODEN: ACACAM; ISSN:0003-2670. (Elsevier B.V.)Au Nanostar (NS) monolayer as a surface enhanced Raman scattering (SERS) substrate was synthesized by self-assembly at a H2O-oil interface. It is confirmed from the expt. and simulation results that the Au NS monolayer includes lots of hot spots at or between the tips of the Au NSs, enhancing the local electromagnetic fields and giving rise to strong SERS signals sequentially. The limit of detection is down to 4.2 × 10-12 M for rhodamine 6G. Also, the Au NS monolayer can detect multiple mols., including thiabendazole, methylene blue, 4-mercaptobenzoic acid, and p-amino thiophenol, indicating that the SERS substrate composed of Au NS monolayer has potential applications in anal. chem., food safety, and environmental safety.
- 70Ma, Y.; Liu, H.; Mao, M.; Meng, J.; Yang, L.; Liu, J. Surface-Enhanced Raman Spectroscopy on Liquid Interfacial Nanoparticle Arrays for Multiplex Detecting Drugs in Urine. Anal. Chem. 2016, 88, 8145– 8151, DOI: 10.1021/acs.analchem.6b0188470Surface-Enhanced Raman Spectroscopy on Liquid Interfacial Nanoparticle Arrays for Multiplex Detecting Drugs in UrineMa, Yongmei; Liu, Honglin; Mao, Mei; Meng, Juan; Yang, Liangbao; Liu, JinhuaiAnalytical Chemistry (Washington, DC, United States) (2016), 88 (16), 8145-8151CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)The design and application of liq. interfacial plasmonic platform is still in its infancy but is an exciting topic in tunable optical devices, sensors, and catalysis. Here, we developed an interfacial surface-enhanced Raman scattering (SERS) platform through the large-scale self-assembly of gold nanoparticle (GNP) arrays at the cyclohexane (CYH)/water interface for detecting trace drug mols. in the urine of humans. The mols. extd. by the CYH phase from a urine sample were directly localized into the self-organized plasmonic hotspots, yielded excellent Raman enhancement, and realized the substrate-free interfacial SERS detection. Synchrotron radiation small-angle X-ray scattering (SR-SAXS) expts. reveals a good uniformity of approx. 2-3 nm interparticle distance in the GNP arrays. SERS colocalization expts. demonstrated that amphetamine mols. of different concn. levels could be loaded into the interfacial GNP arrays and realized the coassembly together with nanoparticles at the liq./liq. interface. Interfacial GNP arrays with dynamic nanogaps in liq. interfacial structure can make surrounding mols. easily diffuse into the nanogaps. In contrast, the fixed GNP arrays on Si wafer were more irregular, such as multilayer stack, random aggregates, and voids, during the drying process. When the drugs directly participate in the self-assembly process, it becomes easier for analytes diffusing into the nanogaps of GNP arrays, produces a concn. effect, and amplified the SERS sensitivity. This feature also enables mols. to be adsorbed evenly in the arrays and makes a more uniform distribution of both the analytes and GNPs in the liq. interface and realizes the significant increase in signal reproducibility. Interfacial SERS produced a std. deviation of 12.5% at 1001 cm-1 peak of methamphetamine (MAMP) mols. under the concn. of 1 ppm, implying a good reproducibility. Moreover, dual-analyte detection at org. and aq. phases was also realized and confirmed a good capability for analytes detection by liq. interfacial SERS platform, which promises nonengineering detection of analytes dissolved in often-inaccessible environments.
- 71Zhang, C.; You, E.; Jin, Q.; Yuan, Y.; Xu, M.; Ding, S.; Yao, J.; Tian, Z. Observing the dynamic “hot spots” on two-dimensional Au nanoparticles monolayer film. Chem. Commun. 2017, 53, 6788– 6791, DOI: 10.1039/C7CC03020G71Observing the dynamic "hot spots" on two-dimensional Au nanoparticles monolayer filmZhang, Chenjie; You, Enming; Jin, Qi; Yuan, Yaxian; Xu, Minmin; Ding, Songyuan; Yao, Jianlin; Tian, ZhongqunChemical Communications (Cambridge, United Kingdom) (2017), 53 (50), 6788-6791CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)Interparticle spacing was controlled by evapg. water on 2D Au nanoparticles arrays. Relationships among SERS effect, SPR catalysis, and gap distance were exptl. and theor. studied.
- 72Kelly, J.; Patrick, R.; Patrick, S.; Bell, S. E. J. Surface-Enhanced Raman Spectroscopy for the Detection of a Metabolic Product in the Headspace Above Live Bacterial Cultures. Angew. Chem., Int. Ed. 2018, 57, 15686– 15690, DOI: 10.1002/anie.20180818572Surface-Enhanced Raman Spectroscopy for the Detection of a Metabolic Product in the Headspace Above Live Bacterial CulturesKelly, Jessica; Patrick, Robin; Patrick, Sheila; Bell, Steven E. J.Angewandte Chemie, International Edition (2018), 57 (48), 15686-15690CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)In situ surface-enhanced Raman spectra of the headspace above cultures of six bacterial species showed strong characteristic bands from chemisorbed Me sulfide. This marker compd. is created by dissocn. of di-Me disulfide (DMDS), a fermentative metabolite of bacteria, on the surface of the enhancing Au or Ag nanoparticle films. Kinetic binding plots of media spiked with DMDS and of live cultures showed that the Au-based substrates were more suitable for the rapid detection of bacteria than Ag-based substrates. For E. coli DH5α, the sensitivity limit for headspace SERS detection was 1.5×107 CFU mL-1, which corresponded to detection 15 min after inoculation of the growth medium. Since the metabolites are only produced by viable bacteria, antibiotic (gentamicin) treatment stopped the normal signal growth of the marker peak. This work is a promising step towards rapid bedside detection of bacterial infections and rapid screening of antibiotics against bacteria.
- 73Li, C.; Zhang, Y.; Ye, Z.; Bell, S. E. J.; Xu, Y. Combining surface-accessible Ag and Au colloidal nanomaterials with SERS for in situ analysis of molecule–metal interactions in complex solution environments. Nat. Protoc 2023, 18, 2717– 2744, DOI: 10.1038/s41596-023-00851-6There is no corresponding record for this reference.
- 74Zhong, Y.; Moore, T. C.; Dwyer, T.; Butrum-Griffith, A.; Allen, V. R.; Chen, J.; Wang, Y.; Cheng, F.; Glotzer, S. C.; Ye, X. Engineering and direct imaging of nanocube self-assembly pathways. Nature Chemical Engineering 2024, 1, 532– 541, DOI: 10.1038/s44286-024-00102-9There is no corresponding record for this reference.
- 75Li, C.; Chai, L.; Chen, Q.; Ye, Z.; Xu, Y.; Bell, S. E. J. Superhydrophobic needles tipped with 2-dimensional arrays of plasmonic colloidal nanoparticles for microdroplet SERS analysis. J. Raman Spectrosc. 2021, 52, 386– 393, DOI: 10.1002/jrs.599275Superhydrophobic needles tipped with 2-dimensional arrays of plasmonic colloidal nanoparticles for microdroplet SERS analysisLi, Chunchun; Chai, Lin; Chen, Qinglu; Ye, Ziwei; Xu, Yikai; Bell, Steven E. J.Journal of Raman Spectroscopy (2021), 52 (2), 386-393CODEN: JRSPAF; ISSN:0377-0486. (John Wiley & Sons Ltd.)Aq. microdroplets strongly attach to metallic needles with superhydrophobic sides and flat hydrophilic tips. Such needles can be made surface-enhanced Raman spectroscopy (SERS)-active by adsorbing a layer of densely packed and uniform plasmonic nanoparticles onto the hydrophilic tip. The resulting particle-tipped needles allow dual enhancement of the Raman signals from microdroplets of low concn. analytes by combining analyte enrichment through solvent evapn. and plasmonic SERS enhancement. The combination of small sample vol., preconcn., and SERS allows extremely low total amts. of analytes to be detected. Here, we show that with crystal violet as the model analyte, the limit of detection can reach 2 pg. The method can be readily used to fabricate superhydrophobic needles tipped with different types of plasmonic colloidal nanoparticles for enhanced Raman anal., for example, silver cube tipped needles could be used to detect as little as 2.5 ng of trinitrotoluene.
- 76Zhang, L.; Li, X.; Liu, W.; Hao, R.; Jia, H.; Dai, Y.; Usman Amin, M.; You, H.; Li, T.; Fang, J. Highly active Au NP microarray films for direct SERS detection. Journal of Materials Chemistry C 2019, 7, 15259– 15268, DOI: 10.1039/C9TC04848KThere is no corresponding record for this reference.
- 77Kim, K.; Han, H. S.; Choi, I.; Lee, C.; Hong, S.; Suh, S.-H.; Lee, L. P.; Kang, T. Interfacial liquid-state surface-enhanced Raman spectroscopy. Nat. Commun. 2013, 4, 2182, DOI: 10.1038/ncomms318277Interfacial liquid-state surface-enhanced Raman spectroscopyKim Kihoon; Han Hye Soo; Choi Inhee; Lee Chiwon; Hong SoonGweon; Suh Sang-Hee; Lee Luke P; Kang TaewookNature communications (2013), 4 (), 2182 ISSN:.Oriented assemblies of functional nanoparticles, with the aid of external physical and chemical driving forces, have been prepared on two-dimensional solid substrates. It is challengeable, however, to achieve three-dimensional assembly directly in solution, owing to thermal fluctuations and free diffusion. Here we describe the self-orientation of gold nanorods at an immiscible liquid interface (that is, oleic acid-water) and exploit this novel phenomenon to create a substrate-free interfacial liquid-state surface-enhanced Raman spectroscopy. Dark-field imaging and Raman scattering results reveal that gold nanorods spontaneously adopt a vertical orientation at an oleic acid-water interface in a stable trapping mode, which is in good agreement with simulation results. The spontaneous vertical alignment of gold nanorods at the interface allows one to accomplish significant additional amplification of the Raman signal, which is up to three to four orders of magnitude higher than that from a solution of randomly oriented gold nanorods.
- 78Zhang, K.; Zhao, J.; Xu, H.; Li, Y.; Ji, J.; Liu, B. Multifunctional Paper Strip Based on Self-Assembled Interfacial Plasmonic Nanoparticle Arrays for Sensitive SERS Detection. ACS Appl. Mater. & Interfaces 2015, 7, 16767– 16774, DOI: 10.1021/acsami.5b04534There is no corresponding record for this reference.
- 79Luo, W.; Wu, C.; Huang, S.; Luo, X.; Yuan, R.; Yang, X. Liquid Phase Interfacial Surface-Enhanced Raman Scattering Platform for Ratiometric Detection of MicroRNA 155. Anal. Chem. 2020, 92, 15573– 15578, DOI: 10.1021/acs.analchem.0c0363379Liquid Phase Interfacial Surface-Enhanced Raman Scattering Platform for Ratiometric Detection of MicroRNA 155Luo, Wei; Wu, Caijun; Huang, Siqi; Luo, Xiliang; Yuan, Ruo; Yang, XiaAnalytical Chemistry (Washington, DC, United States) (2020), 92 (23), 15573-15578CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)The self-assembly of gold nanoparticles (Au NPs) on a liq. phase interface is often employed as a surface-enhanced Raman scattering (SERS) platform with advantages of simple prepn., high reproducibility, and a defect-free character, but they are limited to only detect a target with Raman signals. To overcome this problem, microRNA 155 without a Raman signal can be detected by a liq. phase interfacial ratiometric SERS platform. Compared with the typical solid phase SERS platform, we propose a distinctive strategy not only owning the advantages of the liq. phase interfacial platform but also breaking the limitation of recent liq.-liq. interfacial SERS anal. This platform presents a fabulous sensitivity with a limit of detection (LOD) of 1.10 aM for microRNA 155. By simply altering the duplex-specific nuclease (DSN) enzyme amplification, our strategy can realize detection of a variety of microRNAs, paving the way to practical applications of a liq. phase SERS platform.
- 80Dong, J.; Yang, C.; Wu, H.; Wang, Q.; Cao, Y.; Han, Q.; Gao, W.; Wang, Y.; Qi, J.; Sun, M. Two-Dimensional Self-Assembly of Au@Ag Core–Shell Nanocubes with Different Permutations for Ultrasensitive SERS Measurements. ACS Omega 2022, 7, 3312– 3323, DOI: 10.1021/acsomega.1c0545280Two-Dimensional Self-Assembly of Au@Ag Core-Shell Nanocubes with Different Permutations for Ultrasensitive SERS MeasurementsDong, Jun; Yang, Chengyuan; Wu, Haoran; Wang, Qianying; Cao, Yi; Han, Qingyan; Gao, Wei; Wang, Yongkai; Qi, Jianxia; Sun, MengtaoACS Omega (2022), 7 (4), 3312-3323CODEN: ACSODF; ISSN:2470-1343. (American Chemical Society)Different self-assembly methods not only directly change the arrangement of noble metal particles on the substrate but also indirectly affect the local electromagnetic field distribution and intensity of the substrate under specific optical excitation conditions, which leads to distinguished different enhancement effects of the structure on mol. Raman signals. In this paper, first, the gold species growth method was used to prep. the silver-coated gold nanocubes (Au@Ag NCs) with regular morphol. and uniform size, and then the two-phase and three-phase liq.-liq. self-assembly and evapn.-induced self-assembly methods were used to obtain the substrate structure with different NC arrangement patterns. The optimal arrangement of NCs was found by transverse comparison of Raman signal detection of probe mols. with the same concn. Subsequently, surface-enhanced Raman scattering (SERS) measurements of Rhodamine (Rh6G) and aspartame (APM) were carried out. Furthermore, the finite element method (FEM) was employed to calc. the local electromagnetic fields of the substrates with different Au@Ag NC arrangements, and the calcd. results were in agreement with the exptl. results. The exptl. results show that the SERS-active substrate was largely assocd. with the different arrangements of Au@Ag NCs, and the island membrane Au@Ag NCs array substrate obtained by evapn.-induced self-assembly can generate a strong local electromagnetic field due to the edge and corner bonding gap between the tightly arranged NCs; this endows the substrate with benign sensitivity and reproducibility and has great potential in mol. detection, biosensing, and food safety monitoring.
- 81Chen, X.; Cui, A.; He, M.; Yan, M.; Zhang, X.; Ruan, J.; Yang, S. Slippery Au Nanosphere Monolayers with Analyte Enrichment and SERS Enhancement Functions. Nano Lett. 2023, 23, 6736– 6743, DOI: 10.1021/acs.nanolett.3c02238There is no corresponding record for this reference.
- 82Zhang, K.; Ji, J.; Li, Y.; Liu, B. Interfacial Self-Assembled Functional Nanoparticle Array: A Facile Surface-Enhanced Raman Scattering Sensor for Specific Detection of Trace Analytes. Anal. Chem. 2014, 86, 6660– 6665, DOI: 10.1021/ac501383x82Interfacial Self-Assembled Functional Nanoparticle Array: A Facile Surface-Enhanced Raman Scattering Sensor for Specific Detection of Trace AnalytesZhang, Kun; Ji, Ji; Li, Yixin; Liu, BaohongAnalytical Chemistry (Washington, DC, United States) (2014), 86 (13), 6660-6665CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Surface-enhanced Raman scattering (SERS) has proven to be promising for the detection of trace analytes; however, the precise nanofabrication of a specific and sensitive plasmonic SERS-active substrate is still a major challenge that limits the scope of its applications. In this work, gold nanoparticles are self-assembled into densely packed two-dimensional arrays at a liq./liq. interface between di-Me carbonate and water in the absence of template controller mols. Both the simulation and expt. results show that the particles within these film-like arrays exhibit strong electromagnetic coupling and enable large amplification of Raman signals. In order to realize the level of sensing specificity, the surface chem. of gold nanoparticles (Au NPs) is rationally tailored by incorporating an appropriate chem. moiety that specifically captures mols. of interest. The ease of fabrication and good uniformity make this platform ideal for in situ SERS sensing of trace targets in complex samples.
- 83Lee, Y. H.; Shi, W.; Lee, H. K.; Jiang, R.; Phang, I. Y.; Cui, Y.; Isa, L.; Yang, Y.; Wang, J.; Li, S.; Ling, X. Y. Nanoscale surface chemistry directs the tunable assembly of silver octahedra into three two-dimensional plasmonic superlattices. Nat. Commun. 2015, 6, 6990, DOI: 10.1038/ncomms799083Nanoscale surface chemistry directs the tunable assembly of silver octahedra into three two-dimensional plasmonic superlatticesLee, Yih Hong; Shi, Wenxiong; Lee, Hiang Kwee; Jiang, Ruibin; Phang, In Yee; Cui, Yan; Isa, Lucio; Yang, Yijie; Wang, Jianfang; Li, Shuzhou; Ling, Xing YiNature Communications (2015), 6 (), 6990CODEN: NCAOBW; ISSN:2041-1723. (Nature Publishing Group)A major challenge in nanoparticle self-assembly is programming the large-area organization of a single type of anisotropic nanoparticle into distinct superlattices with tunable packing efficiencies. Here we utilize nanoscale surface chem. to direct the self-assembly of silver octahedra into three distinct two-dimensional plasmonic superlattices at a liq./liq. interface. Systematically tuning the surface wettability of silver octahedra leads to a continuous superlattice structural evolution, from close-packed to progressively open structures. Notably, silver octahedra standing on vertices arranged in a square lattice is obsd. using hydrophobic particles. Simulations reveal that this structural evolution arises from competing interfacial forces between the particles and both liq. phases. Structure-to-function characterizations reveal that the standing octahedra array generates plasmonic 'hotstrips', leading to nearly 10-fold more efficient surface-enhanced Raman scattering compared with the other more densely packed configurations. The ability to assemble these superlattices on the wafer scale over various platforms further widens their potential applications.
- 84Zhao, W.; Zhang, Y.; Yang, J.; Li, J.; Feng, Y.; Quan, M.; Yang, Z.; Xiao, S. Synergistic plasmon resonance coupling and light capture in ordered nanoarrays as ultrasensitive and reproducible SERS substrates. Nanoscale 2020, 12, 18056– 18066, DOI: 10.1039/D0NR02972F84Synergistic plasmon resonance coupling and light capture in ordered nanoarrays as ultrasensitive and reproducible SERS substratesZhao, Weidong; Zhang, Yuxian; Yang, Jiajia; Li, Jinming; Feng, Yun; Quan, Maohua; Yang, Zhou; Xiao, ShuyuanNanoscale (2020), 12 (35), 18056-18066CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)An effective SERS substrate for on-field detection needs to satisfy high sensitivity to analyte and signal reproducibility even in the special case of tilting or bending of substrates. Herein, we transferred monolayer AuNPs into a nanocavity to construct a Au particle-in-hemispherical honeycomb nanoarray (PIHHN) as an ultrasensitive and spatially reproducible SERS substrate. The capacity of detection for R6G in an optimal PIHHN substrate is as low as a concn. of 10-15 M, and the RSD of signal deviation is no more than 5.6%. FDTD simulations explain that placing AuNPs into a metallic nanocavity can capture and focus the light field to improve the interaction between the light and the substrate and provide the collective effect of multiple plasmon coupling, which can induce a stronger electromagnetic field. In addn., the system can generate more hot spots between AuNPs and between AuNPs and the metallic nanocavity. In particular, when the substrate is tilted or bent at an angle from 0° to 60°, the SERS performance remains stable due to the rotational symmetry of the PIHHN structure, which demonstrates the capability of on-field detection. Furthermore, the PIHHN substrate is employed as a highly sensitive multiplex sensor in on-field anal. for contaminated soil, achieving the detection of analytes down to 0.5 ppb.
- 85Su, M.; Jiang, Q.; Guo, J.; Zhu, Y.; Cheng, S.; Yu, T.; Du, S.; Jiang, Y.; Liu, H. Quality alert from direct discrimination of polycyclic aromatic hydrocarbons in edible oil by liquid-interfacial surface-enhanced Raman spectroscopy. LWT 2021, 143, 111143, DOI: 10.1016/j.lwt.2021.111143There is no corresponding record for this reference.
- 86Lee, Y. H.; Lee, C. K.; Tan, B.; Rui Tan, J. M.; Phang, I. Y.; Ling, X. Y. Using the Langmuir–Schaefer technique to fabricate large-area dense SERS-active Au nanoprism monolayer films. Nanoscale 2013, 5, 6404– 6412, DOI: 10.1039/c3nr00981e86Using the Langmuir-Schaefer technique to fabricate large-area dense SERS-active Au nanoprism monolayer filmsLee, Yih Hong; Lee, Choon Keong; Tan, Baorui; Tan, Joel Ming Rui; Phang, In Yee; Ling, Xing YiNanoscale (2013), 5 (14), 6404-6412CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)Interfacial self-assembly of nanoparticles is capable of creating large-area close-packed structures for a variety of applications. However, monolayers of hydrophilic cetyltrimethylammonium bromide (CTAB)-coated Au nanoparticles are challenging to assemble via interfacial self-assembly. This report presents a facile and scalable process to fabricate large-area monolayer films of ultrathin CTAB-coated Au nanoprisms at the air-water interface using the Langmuir-Schaefer technique. This is first achieved by a one-step functionalization of Au nanoprisms with poly(vinylpyrrolidone) (PVP). PVP functionalization is completed within a short time without loss of nanoprisms due to aggregation. Uniform and near close-packed monolayers of the Au nanoprisms formed over large areas (∼1 cm2) at the air-water interface can be transferred to substrates with different wettabilities. The inter-prism gaps are tuned qual. through the introduction of dodecanethiol and oleylamine. The morphol. integrity of the nanoprisms is maintained throughout the entire assembly process, without truncation of the nanoprism tips. The near close-packed arrangement of the nanoprism monolayers generates large nos. of hot spots in the 2D arrays in the tip-to-tip and edge-to-edge inter-particle regions, giving rise to strong surface-enhanced Raman scattering (SERS) signals. When deposited on an Au mirror film, addnl. hotspots are created in the 3rd dimension in the gaps between the 2D nanoprism monolayers and the Au film. SERS enhancement factors reaching 104 for non-resonant probe mols. are achieved.
- 87Zhang, H.; Wei, J.; Zhang, X.-G.; Zhang, Y.-J.; Radjenovica, P. M.; Wu, D.-Y.; Pan, F.; Tian, Z.-Q.; Li, J.-F. Plasmon-Induced Interfacial Hot-Electron Transfer Directly Probed by Raman Spectroscopy. Chem. 2020, 6, 689– 702, DOI: 10.1016/j.chempr.2019.12.01587Plasmon-Induced Interfacial Hot-Electron Transfer Directly Probed by Raman SpectroscopyZhang, Hua; Wei, Jie; Zhang, Xia-Guang; Zhang, Yue-Jiao; Radjenovica, Petar M.; Wu, De-Yin; Pan, Feng; Tian, Zhong-Qun; Li, Jian-FengChem (2020), 6 (3), 689-702CODEN: CHEMVE; ISSN:2451-9294. (Cell Press)Plasmon-mediated photocatalysis via hot-electron transfer attracts increasing interest due to its capability to improve energy utilization efficiency. However, more insightful information is still needed to reveal the mechanism of interfacial hot-electron transfer. Herein, the plasmon-induced hot-electron transfer at different plasmonic interfaces, including Au-insulator (SiO2), Au-semiconductor (TiO2 and Cu2O), and Au-metal (Pd and Pt), is directly investigated using surface-enhanced Raman spectroscopy (SERS) and d. functional theory calcn. with a (sub)nanometer spatial resoln., through the fabrication of well-defined plasmonic nanostructures. (Sub)nanometer-distance dependence of interfacial hot-electron transfer has been identified for the first time. Hot electrons can migrate across the Au-semiconductor or Au-metal interfaces and transfer more than 10 nm in semiconductors but decay to thermally equilibrated states rapidly in metals in less than 1 nm. Such a transfer process is blocked at the Au-insulator interface. This work promotes the fundamental understanding of plasmon-induced hot-electron transmission and photocatalysis at plasmonic interfaces.
- 88Liu, H. L.; Yang, Z. L.; Meng, L.; Sun, Y.; Wang, J.; Yang, L.; Liu, J.; Tian, Z. Three-Dimensional and Time-Ordered Surface-Enhanced Raman Scattering Hotspot Matrix. J. Am. Chem. Soc. 2014, 136, 5332– 5341, DOI: 10.1021/ja501951v88Three-Dimensional and Time-Ordered Surface-Enhanced Raman Scattering Hotspot MatrixLiu, Honglin; Yang, Zhilin; Meng, Lingyan; Sun, Yudie; Wang, Jie; Yang, Liangbao; Liu, Jinhuai; Tian, ZhongqunJournal of the American Chemical Society (2014), 136 (14), 5332-5341CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)The "fixed" or "flexible" design of plasmonic hotspots is a frontier area of research in the field of surface-enhanced Raman scattering (SERS). Most reported SERS hotspots have been shown to exist in zero-dimensional point-like, one-dimensional linear, or two-dimensional planar geometries. Here, we demonstrate a novel three-dimensional (3D) hotspot matrix that can hold hotspots between every two adjacent particles in 3D space, simply achieved by evapg. a droplet of citrate-Ag sols on a fluorosilylated silicon wafer. In situ synchrotron-radiation small-angle X-ray scattering (SR-SAXS), combined with dark-field microscopy and in situ micro-UV, was employed to explore the evolution of the 3D geometry and plasmonic properties of Ag nanoparticles in a single droplet. In such a droplet, there is a distinct 3D geometry with minimal polydispersity of particle size and maximal uniformity of interparticle distance, significantly different from the dry state. According to theor. simulations, the liq. adhesive force promotes a closely packed assembly of particles, and the interparticle distance is not fixed but can be balanced in a small range by the interplay of the van der Waals attraction and electrostatic repulsion experienced by a particle. The "trapping well" for immobilizing particles in 3D space can result in a large no. of hotspots in a 3D geometry. Both theor. and exptl. results demonstrate that the 3D hotspots are predictable and time-ordered in the absence of any sample manipulation. Use of the matrix not only produces giant Raman enhancement at least 2 orders of magnitude larger than that of dried substrates, but also provides the structural basis for trapping mols. Even a single mol. of resonant dye can generate a large SERS signal. With a portable Raman spectrometer, the detection capability is also greatly improved for various analytes with different natures, including pesticides and drugs. This 3D hotspot matrix overcomes the long-standing limitations of SERS for the ultrasensitive characterization of various substrates and analytes and promises to transform SERS into a practical anal. technique.
- 89Ge, M. H.; Li, P.; Cao, C. T.; Li, S. F.; Lin, D. Y.; Yang, L. B. A long-period and high-stability three-dimensional surface-enhanced Raman scattering hotspot matrix. Chem. Commun. 2019, 55, 8647– 8650, DOI: 10.1039/C9CC02980J89A long-period and high-stability three-dimensional surface-enhanced Raman scattering hotspot matrixGe, Meihong; Li, Pan; Cao, Chentai; Li, Shaofei; Lin, Dongyue; Yang, LiangbaoChemical Communications (Cambridge, United Kingdom) (2019), 55 (59), 8647-8650CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)A novel long-period and high-stability 3D hotspot matrix was constructed with the assistance of glycerol based on our previous study on the dynamic-SERS approach in the water system: it could increase efficient hotspot duration from few seconds to twenty minutes and strongly improve sensitivity and reproducibility for SERS detection.
- 90Chen, X.; Ding, Q.; Bi, C.; Ruan, J.; Yang, S. Lossless Enrichment of Trace Analytes in Levitating Droplets for Multiphase and Multiplex Detection. Nat. Commun. 2022, 13, 7807, DOI: 10.1038/s41467-022-35495-990Lossless enrichment of trace analytes in levitating droplets for multiphase and multiplex detectionChen, Xueyan; Ding, Qianqian; Bi, Chao; Ruan, Jian; Yang, ShikuanNature Communications (2022), 13 (1), 7807CODEN: NCAOBW; ISSN:2041-1723. (Nature Portfolio)Concg. a trace amt. of mols. from liqs., solid objects, or the gas phase and delivering them to a localized area are crucial for almost any trace analyte detection device. Analytes within a liq. droplet resting on micro/nanostructured surfaces with liq.-repellent coatings can be concd. during solvent evapn. However, these coatings suffer from complex manufg. procedures, poor versatility, and limited analyte enrichment efficiency. Here, we report on the use of an acoustic levitation platform to losslessly conc. the analyte mols. dissolved in any volatile liq., attached to solid objects, or spread in air. Gold nanoparticles can be simultaneously concd. with the analytes in different phases, realizing sensitive, surface-enhanced Raman scattering detection even at attomolar (10-18 mol/L) concn. levels. The acoustic levitation platform-enabled, lossless analyte enrichment can significantly increase the anal. performance of many conventional microsensing techniques.
- 91Yang, L. B.; Li, P.; Liu, H. L.; Tang, X. H.; Liu, J. H. A dynamic surface enhanced Raman spectroscopy method for ultra-sensitive detection: from the wet state to the dry state. Chem. Soc. Rev. 2015, 44, 2837– 2848, DOI: 10.1039/C4CS00509K91A dynamic surface enhanced Raman spectroscopy method for ultra-sensitive detection: from the wet state to the dry stateYang, Liangbao; Li, Pan; Liu, Honglin; Tang, Xianghu; Liu, JinhuaiChemical Society Reviews (2015), 44 (10), 2837-2848CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)Surface-enhanced Raman spectroscopy (SERS) has been demonstrated to be an excellent anal. tool for a wide range of research and practical applications owing to its ability to achieve highly sensitive detection and provide fingerprint information for analytes. Improving the sensitivity of SERS is beneficial for the rapid anal. of target mols. in various systems, where the ultimate goal is to obtain quant. anal. and detection. Considerable efforts have been made to develop new methods for SERS detection that improve upon its high sensitivity and reproducibility. In this tutorial review, we first introduce the traditional methods for SERS detection and then report in detail on the features of a new strategy for implementing SERS. This new method, namely, a dynamic surface-enhanced Raman spectroscopy method proposed by our group, is based on state translation nanoparticle-enhanced Raman spectroscopy (STNERS) from the wet state to the dry state. Notably, during this process, a three-dimensional (3D) hotspot matrix that can hold hotspots between every two adjacent particles in 3D space, with minimal polydispersity of the particle size and maximal uniformity of the interparticle distance, can be simply achieved. Expts. and applications using STNERS are reviewed starting with an investigation of STNERS mechanisms and a discussion of sample prepn. Next, evidence of the advantages of STNERS and practical applications are discussed. Finally, the future outlook for STNERS and the development of STNERS as an ultra-sensitive detection method are also discussed.
- 92Zhou, G. L.; Li, P.; Ge, M. H.; Wang, J. P.; Chen, S. Y.; Nie, Y. M.; Wang, Y. X.; Qin, M.; Huang, G. Y.; Lin, D. Y.; Wang, H. Z.; Yang, L. B. Controlling the Shrinkage of 3D Hot Spot Droplets as a Microreactor for Quantitative SERS Detection of Anticancer Drugs in Serum Using a Handheld Raman Spectrometer. Anal. Chem. 2022, 94, 4831– 4840, DOI: 10.1021/acs.analchem.2c0007192Controlling the Shrinkage of 3D Hot Spot Droplets as a Microreactor for Quantitative SERS Detection of Anticancer Drugs in Serum Using a Handheld Raman SpectrometerZhou, Guoliang; Li, Pan; Ge, Meihong; Wang, Junping; Chen, Siyu; Nie, Yuman; Wang, Yaoxiong; Qin, Miao; Huang, Guangyao; Lin, Dongyue; Wang, Hongzhi; Yang, LiangbaoAnalytical Chemistry (Washington, DC, United States) (2022), 94 (11), 4831-4840CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Quant. measurement is one of the ultimate targets for surface-enhanced Raman spectroscopy (SERS), but it suffers from difficulties in controlling the uniformity of hot spots and placing the target mols. in the hot spot space. Here, a convenient approach of three-phase equil. controlling the shrinkage of three-dimensional (3D) hot spot droplets has been demonstrated for the quant. detection of the anticancer drug 5-fluorouracil (5-FU) in serum using a handheld Raman spectrometer. Droplet shrinkage, triggered by the shaking of aq. nanoparticle (NP) colloids with immiscible oil chloroform (CHCl3) after the addn. of neg. ions and acetone, not only brings the nanoparticles in close proximity but can also act as a microreactor to enhance the spatial enrichment capability of the analyte in plasmonic sites and thereby realize simultaneously controlling 3D hot spots and placing target mols. in hot spots. Moreover, the shrinking process of Ag colloid droplets has been investigated using a high-speed camera, an in situ transmission electron microscope (in situ TEM), and a dark-field microscope (DFM), demonstrating the high stability and uniformity of nanoparticles in droplets. The shrunk Ag NP droplets exhibit excellent SERS sensitivity and reproducibility for the quant. anal. of 5-FU over a large range of 50-1000 ppb. Hence, it is promising for quant. anal. of complex systems and long-term monitoring of bioreactions.
- 93Ge, M. H.; Li, P.; Zhou, G. L.; Chen, S. Y.; Han, W.; Qin, F.; Nie, Y. M.; Wang, Y. X.; Qin, M.; Huang, G. Y.; Li, S. F.; Wang, Y. T.; Yang, L. B.; Tian, Z. Q. General Surface-Enhanced Raman Spectroscopy Method for Actively Capturing Target Molecules in Small Gaps. J. Am. Chem. Soc. 2021, 143, 7769– 7776, DOI: 10.1021/jacs.1c0216993General Surface-Enhanced Raman Spectroscopy Method for Actively Capturing Target Molecules in Small GapsGe, Meihong; Li, Pan; Zhou, Guoliang; Chen, Siyu; Han, Wei; Qin, Feng; Nie, Yuman; Wang, Yaoxiong; Qin, Miao; Huang, Guangyao; Li, Shaofei; Wang, Yongtao; Yang, Liangbao; Tian, ZhongqunJournal of the American Chemical Society (2021), 143 (20), 7769-7776CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Over the past decade, many efforts have been devoted to designing and fabricating substrates for surface-enhanced Raman spectroscopy (SERS) with abundant hot spots to improve the sensitivity of detection. However, there have been many difficulties involved in causing mols. to enter hot spots actively or effectively. Here, we report a general SERS method for actively capturing target mols. in small gaps (hot spots) by constructing a nanocapillary pumping model. The ubiquity of hot spots and the inevitability of mols. entering them lights up all the hot spots and makes them effective. This general method can realize the highly sensitive detection of different types of mols., including org. pollutants, drugs, poisons, toxins, pesticide residues, dyes, antibiotics, amino acids, antitumor drugs, explosives, and plasticizers. Addnl., in the dynamic detection process, an efficient and stable signal can be maintained for 1-2 min, which increases the practicality and operability of this method. Moreover, a dynamic detection process like this corresponds to the processes of material transformation in some organisms, so the method can be used to monitor transformation processes such as the death of a single cell caused by photothermal stimulation. Our method provides a novel pathway for generating hot spots that actively attract target mols., and it can achieve general ultratrace detection of diverse substances and be applied to the study of cell behaviors in biol. systems.
- 94Wang, W.; Pu, S.; Hu, W.; Gu, J.; Ren, B.; Tian, Z.; Liu, G. Revealing the synergistic effect of capillary force and electrostatic attraction for D-SERS sensitivity. Chem. Commun. (Camb) 2022, 58, 3953– 3956, DOI: 10.1039/D2CC00824FThere is no corresponding record for this reference.
- 95Qin, M.; Ge, M.; Li, P.; Chen, S.; Huang, G.; Tong, X.; Han, W.; Ren, D.; He, Y.; Lin, D.; Yang, L.; Tian, Z. Natural < 3 nm Interbedded Gaps to Trap Target Molecules and Provide an Enhanced Raman Spectroscopy Method. Advanced Optical Materials 2022, 10, 2200551, DOI: 10.1002/adom.202200551There is no corresponding record for this reference.
- 96Chen, S.; Ge, M.; Weng, S.; Li, J.; Huang, Y.; Li, P.; Yang, L. Development of a MoS(2)/Ag NP Nanopocket to Trap Target Molecules for Surface-Enhanced Raman Scattering Detection with Long-Term Stability and High Sensitivity. Anal. Chem. 2023, 95, 10257– 10264, DOI: 10.1021/acs.analchem.3c00665There is no corresponding record for this reference.
- 97Deegan, R. D.; Bakajin, O.; Dupont, T. F.; Huber, G.; Nagel, S. R.; Witten, T. A. Capillary Flow as the Cause of Ring Stains from Dried Liquid Drops. Nature 1997, 389, 827– 829, DOI: 10.1038/3982797Capillary flow as the cause of ring stains from dried liquid dropsDeegan, Robert D.; Bakajin, Olgica; Dupont, Todd F.; Huber, Greg; Nagel, Sidney R.; Witten, Thomas A.Nature (London) (1997), 389 (6653), 827-829CODEN: NATUAS; ISSN:0028-0836. (Macmillan Magazines)When a spilled drop of coffee dries on a solid surface, it leaves a dense, ring-like deposit along the perimeter. The coffee - initially dispersed over the entire drop - becomes concd. into a tiny fraction of it. Such ring deposits are common wherever drops contg. dispersed solids evap. on a surface, and they influence processes such as printing, washing and coating. Ring deposits also provide a potential means to write or deposit a fine pattern onto a surface. Here we ascribe the characteristic pattern of the deposition to a form of capillary flow in which pinning of the contact line of the drying drop ensures that liq. evapg. from the edge is replenished by liq. from the interior. The resulting outward flow can carry virtually all the dispersed material to the edge. This mechanism predicts a distinctive power-law growth of the ring mass with time - a law independent of the particular substrate, carrier fluid or deposited solids. We have verified this law by microscopic observations of colloidal fluids.
- 98De Angelis, F.; Gentile, F.; Mecarini, F.; Das, G.; Moretti, M.; Candeloro, P.; Coluccio, M. L.; Cojoc, G.; Accardo, A.; Liberale, C.; Zaccaria, R. P.; Perozziello, G.; Tirinato, L.; Toma, A.; Cuda, G.; Cingolani, R.; Di Fabrizio, E. Breaking the Diffusion Limit with Super-Hydrophobic Delivery of Molecules to Plasmonic Nanofocusing SERS Structures. Nat. Photonics 2011, 5, 682– 687, DOI: 10.1038/nphoton.2011.22298Breaking the diffusion limit with super-hydrophobic delivery of molecules to plasmonic nanofocusing SERS structuresDe Angelis, F.; Gentile, F.; Mecarini, F.; Das, G.; Moretti, M.; Candeloro, P.; Coluccio, M. L.; Cojoc, G.; Accardo, A.; Liberale, C.; Zaccaria, R. P.; Perozziello, G.; Tirinato, L.; Toma, A.; Cuda, G.; Cingolani, R.; Di Fabrizio, E.Nature Photonics (2011), 5 (11), 682-687CODEN: NPAHBY; ISSN:1749-4885. (Nature Publishing Group)The detection of a few mols. in a highly dild. soln. is of paramount interest in fields including biomedicine, safety and eco-pollution in relation to rare and dangerous chems. Nanosensors based on plasmonics are promising devices in this regard, in that they combine the features of high sensitivity, label-free detection and miniaturization. However, plasmonic-based nanosensors, in common with general sensors with sensitive areas on the scale of nanometers, cannot be used directly to detect mols. dissolved in femto- or attomolar solns. They are diffusion-limited and their detection times become impractical at such concns. In this Article, the authors demonstrate, by combining super-hydrophobic artificial surfaces and nanoplasmonic structures, that few mols. can be localized and detected even at attomolar (10-18 mol l-1) concn. Also, the detection can be combined with fluorescence and Raman spectroscopy, such that the chem. signature of the mols. can be clearly detd.
- 99Chen, X.; Ma, R.; Li, J.; Hao, C.; Guo, W.; Luk, B. L.; Li, S. C.; Yao, S.; Wang, Z. Evaporation of Droplets on Superhydrophobic Surfaces: Surface Roughness and Small Droplet Size Effects. Phys. Rev. Lett. 2012, 109, 116101, DOI: 10.1103/PhysRevLett.109.11610199Evaporation of droplets on superhydrophobic surfaces: surface roughness and small droplet size effectsChen, Xuemei; Ma, Ruiyuan; Li, Jintao; Hao, Chonglei; Guo, Wei; Luk, B. L.; Li, Shuai Cheng; Yao, Shuhuai; Wang, ZuankaiPhysical Review Letters (2012), 109 (11), 116101/1-116101/6CODEN: PRLTAO; ISSN:0031-9007. (American Physical Society)Evapn. of a sessile droplet is a complex, nonequil. phenomenon. Although evapg. droplets upon superhydrophobic surfaces have been known to exhibit distinctive evapn. modes such as a const. contact line (CCL), a const. contact angle (CCA), or both, our fundamental understanding of the effects of surface roughness on the wetting transition remains elusive. We show that the onset time for the CCL-CCA transition and the crit. base size at the Cassie-Wenzel transition exhibit remarkable dependence on the surface roughness. Through global interfacial energy anal. we reveal that, when the size of the evapg. droplet becomes comparable to the surface roughness, the line tension at the triple line becomes important in the prediction of the crit. base size. Last, we show that both the CCL evapn. mode and the Cassie-Wenzel transition can be effectively inhibited by engineering a surface with hierarchical roughness.
- 100Yang, S.; Dai, X.; Stogin, B. B.; Wong, T.-S. Ultrasensitive Surface-Enhanced Raman Scattering Detection in Common Fluids. Proc. Natl. Acad. Sci. U. S. A. 2016, 113, 268– 273, DOI: 10.1073/pnas.1518980113100Ultrasensitive surface-enhanced Raman scattering detection in common fluidsYang, Shikuan; Dai, Xianming; Stogin, Birgitt Boschitsch; Wong, Tak-SingProceedings of the National Academy of Sciences of the United States of America (2016), 113 (2), 268-273CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)Detecting target analytes with high specificity and sensitivity in any fluid is of fundamental importance to anal. science and technol. Surface-enhanced Raman scattering (SERS) has proven to be capable of detecting single mols. with high specificity, but achieving single-mol. sensitivity in any highly dild. solns. remains a challenge. Here we demonstrate a universal platform that allows for the enrichment and delivery of analytes into the SERS-sensitive sites in both aq. and nonaq. fluids, and its subsequent quant. detection of Rhodamine 6G (R6G) down to ∼75 fM level (10-15 mol·L-1). Our platform, termed slippery liq.-infused porous surface-enhanced Raman scattering (SLIPSERS), is based on a slippery, omniphobic substrate that enables the complete concn. of analytes and SERS substrates (e.g., Au nanoparticles) within an evapg. liq. droplet. Combining our SLIPSERS platform with a SERS mapping technique, we have systematically quantified the probability, p(c), of detecting R6G mols. at concns. c ranging from 750 fM (p > 90%) down to 75 aM (10-18 mol·L-1) levels (p ≤ 1.4%). The ability to detect analytes down to attomolar level is the lowest limit of detection for any SERS-based detection reported thus far. We have shown that analytes present in liq., solid, or air phases can be extd. using a suitable liq. solvent and subsequently detected through SLIPSERS. Based on this platform, we have further demonstrated ultrasensitive detection of chem. and biol. mols. as well as environmental contaminants within a broad range of common fluids for potential applications related to anal. chem., mol. diagnostics, environmental monitoring, and national security.
- 101Wong, T.-S.; Kang, S. H.; Tang, S. K. Y.; Smythe, E. J.; Hatton, B. D.; Grinthal, A.; Aizenberg, J. Bioinspired Self-Repairing Slippery Surfaces with Pressure-Stable Omniphobicity. Nature 2011, 477, 443– 447, DOI: 10.1038/nature10447101Bioinspired self-repairing slippery surfaces with pressure-stable omniphobicityWong, Tak-Sing; Kang, Sung Hoon; Tang, Sindy K. Y.; Smythe, Elizabeth J.; Hatton, Benjamin D.; Grinthal, Alison; Aizenberg, JoannaNature (London, United Kingdom) (2011), 477 (7365), 443-447CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)Creating a robust synthetic surface that repels various liqs. would have broad technol. implications for areas ranging from biomedical devices and fuel transport to architecture but proved extremely challenging. Inspirations from natural nonwetting structures, particularly the leaves of the lotus, led to the development of liq.-repellent microtextured surfaces that rely on the formation of a stable air-liq. interface. Despite over a decade of intense research, these surfaces are, however, still plagued with problems that restrict their practical applications: limited oleophobicity with high contact angle hysteresis, failure under pressure and upon phys. damage, inability to self-heal and high prodn. cost. To address these challenges, here the authors report a strategy to create self-healing, slippery liq.-infused porous surface(s) (SLIPS) with exceptional liq.- and ice-repellency, pressure stability and enhanced optical transparency. The approach-inspired by Nepenthes pitcher plants-is conceptually different from the lotus effect, because the authors use nano/microstructured substrates to lock in place the infused lubricating fluid. The authors define the requirements for which the lubricant forms a stable, defect-free and inert slippery' interface. This surface outperforms its natural counterparts and state-of-the-art synthetic liq.-repellent surfaces in its capability to repel various simple and complex liqs. (water, hydrocarbons, crude oil and blood), maintain low contact angle hysteresis ( < 2.5°), quickly restore liq.-repellency after phys. damage (within 0.1-1 s), resist ice adhesion, and function at high pressures (up to ∼680 atm). These properties are insensitive to the precise geometry of the underlying substrate, making the approach applicable to various inexpensive, low-surface-energy structured materials (such as porous Teflon membrane). The authors envision that these slippery surfaces will be useful in fluid handling and transportation, optical sensing, medicine, and as self-cleaning and anti-fouling materials operating in extreme environments.
- 102Aldeanueva-Potel, P.; Faoucher, E.; Alvarez-Puebla, R. A.; Liz-Marzán, L. M.; Brust, M. Recyclable molecular trapping and SERS detection in silver-loaded agarose gels with dynamic hot spots. Anal. Chem. 2009, 81, 9233– 8, DOI: 10.1021/ac901333p102Recyclable Molecular Trapping and SERS Detection in Silver-Loaded Agarose Gels with Dynamic Hot SpotsAldeanueva-Potel, Paula; Faoucher, Erwan; Alvarez-Puebla, Ramon A.; Liz-Marzan, Luis M.; Brust, MathiasAnalytical Chemistry (Washington, DC, United States) (2009), 81 (22), 9233-9238CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)We describe the design and fabrication of composite agarose gels, highly loaded with silver nanoparticles. Because the gel can collapse upon drying and recover when rehydrated, it can be foreseen as an excellent mech. mol. trap that addnl. gives rise to dynamic hot spots as the network vol. decreases and the silver particles get close to each other, thereby generating the high electromagnetic fields that are needed for ultradetection. Addnl., as silver nanoparticles are phys. trapped inside the polymer network, analytes can be washed out by dialysis when immersed in a washing soln., so that recycling can be achieved. Finally, the use of SERS for ultradetection of dichlorodiphenyl-trichloroethane (DDT) is reported for the first time, demonstrating the ability of this novel nanocomposite material to reversibly sequester nonconventional SERS analytes.
- 103Troncoso-Afonso, L.; Vinnacombe-Willson, G. A.; García-Astrain, C.; Liz-Márzan, L. M. SERS in 3D cell models: a powerful tool in cancer research. Chem. Soc. Rev. 2024, 53, 5118– 5148, DOI: 10.1039/D3CS01049JThere is no corresponding record for this reference.
- 104Jimenez de Aberasturi, D.; Henriksen-Lacey, M.; Litti, L.; Langer, J.; Liz-Marzán, L. M. Using SERS Tags to Image the Three-Dimensional Structure of Complex Cell Models. Adv. Funct. Mater. 2020, 30, 1909655, DOI: 10.1002/adfm.201909655104Using SERS Tags to Image the Three-Dimensional Structure of Complex Cell ModelsJimenez de Aberasturi, Dorleta; Henriksen-Lacey, Malou; Litti, Lucio; Langer, Judith; Liz-Marzan, Luis M.Advanced Functional Materials (2020), 30 (14), 1909655CODEN: AFMDC6; ISSN:1616-301X. (Wiley-VCH Verlag GmbH & Co. KGaA)Methods to image complex 3D cell cultures are limited by issues such as fluorophore photobleaching and decompn., poor excitation light penetration, and lack of complementary techniques to verify the 3D structure. Although it remains insufficiently demonstrated, surface-enhanced Raman scattering (SERS) imaging is a promising tool for the characterization of biol. complex systems. To this aim, a controllable 3D cell culture model which spans nearly 1 cm2 in surface footprint is designed. This structure is composed of fibroblasts contg. SERS-encoded nanoparticles (i.e., SERS tags), arranged in an alternating layered structure. This "sandwich" type structure allows monitoring of the SERS signals in the z-axis and with mm dimensions in the xy-axis. Taking advantage of correlative microscopy techniques such as electron microscopy, it is possible to corroborate nanoparticle positioning and distances in z-depths of up to 150μm. This study reveals a proof-of-concept method for detailed 3D SERS imaging of a complex, dense 3D cell culture model.
- 105García-Astrain, C.; Lenzi, E.; Jimenez de Aberasturi, D.; Henriksen-Lacey, M.; Binelli, M. R.; Liz-Marzán, L. M. 3D-Printed Biocompatible Scaffolds with Built-In Nanoplasmonic Sensors. Adv. Funct. Mater. 2020, 30, 2005407, DOI: 10.1002/adfm.2020054071053D-Printed Biocompatible Scaffolds with Built-In Nanoplasmonic SensorsGarcia-Astrain, Clara; Lenzi, Elisa; Jimenez de Aberasturi, Dorleta; Henriksen-Lacey, Malou; Binelli, Marco R.; Liz-Marzan, Luis M.Advanced Functional Materials (2020), 30 (45), 2005407CODEN: AFMDC6; ISSN:1616-301X. (Wiley-VCH Verlag GmbH & Co. KGaA)3D printing strategies have acquired great relevance toward the design of 3D scaffolds with precise macroporous structures, for supported mammalian cell growth. Despite advances in 3D model designs, there is still a shortage of detection tools to precisely monitor in situ cell behavior in 3D, thereby allowing a better understanding of the progression of diseases or to test the efficacy of drugs in a more realistic microenvironment. Even if the no. of available inks has exponentially increased, they do not necessarily offer the required functionalities to be used as internal sensors. Herein the potential of surface-enhanced Raman scattering (SERS) spectroscopy for the detection of biorelevant analytes within a plasmonic hydrogel-based, 3D-printed scaffold is demonstrated. Such SERS-active scaffolds allow for the 3D detection of model mols., such as 4-mercaptobenzoic acid. Flexibility in the choice of plasmonic nanoparticles is demonstrated through the use of gold nanoparticles with different morphologies, gold nanorods showing the best balance between SERS enhancement and scaffold transparency. Detection of the biomarker adenosine is also demonstrated as a proof-of-concept toward the use of these plasmonic scaffolds for SERS sensing of cell-secreted mols. over extended periods of time.
- 106García-Astrain, C.; Henriksen-Lacey, M.; Lenzi, E.; Renero-Lecuna, C.; Langer, J.; Piñeiro, P.; Molina-Martínez, B.; Plou, J.; Jimenez de Aberasturi, D.; Liz-Marzán, L. M. A Scaffold-Assisted 3D Cancer Cell Model for Surface-Enhanced Raman Scattering-Based Real-Time Sensing and Imaging. ACS Nano 2024, 18, 11257– 11269, DOI: 10.1021/acsnano.4c00543There is no corresponding record for this reference.
- 107González-Callejo, P.; García-Astrain, C.; Herrero-Ruiz, A.; Henriksen-Lacey, M.; Seras-Franzoso, J.; Abasolo, I.; Liz-Marzán, L. M. 3D Bioprinted Tumor-Stroma Models of Triple-Negative Breast Cancer Stem Cells for Preclinical Targeted Therapy Evaluation. ACS Appl. Mater. & Interfaces 2024, 16, 27151– 27163, DOI: 10.1021/acsami.4c04135There is no corresponding record for this reference.
- 108Quintanilla, M.; Henriksen-Lacey, M.; Renero-Lecuna, C.; Liz-Marzán, L. M. Challenges for optical nanothermometry in biological environments. Chem. Soc. Rev. 2022, 51, 4223– 4242, DOI: 10.1039/D2CS00069E108Challenges for optical nanothermometry in biological environmentsQuintanilla, Marta; Henriksen-Lacey, Malou; Renero-Lecuna, Carlos; Liz-Marzan, Luis M.Chemical Society Reviews (2022), 51 (11), 4223-4242CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)Temp. monitoring is useful in medical diagnosis, and essential during hyperthermia treatments to avoid undesired cytotoxic effects. Aiming to control heating doses, different temp. monitoring strategies have been developed, largely based on luminescent materials, a.k.a. nanothermometers. However, for such nanothermometers to work, both excitation and emission light beams must travel through tissue, making its optical properties a relevant aspect to be considered during the measurements. In complex tissues, heterogeneity, and real-time alterations as a result of therapeutic treatment may have an effect on light-tissue interaction, hindering accuracy in the thermal reading. In this Tutorial Review we discuss various methods in which nanothermometers can be used for temp. sensing within heterogeneous environments. We discuss recent developments in optical (nano)thermometry, focusing on the incorporation of luminescent nanoparticles into complex in vitro and in vivo models. Methods formulated to avoid thermal misreading are also discussed, considering their resp. advantages and drawbacks.
- 109Lenzi, E.; Jimenez de Aberasturi, D.; Liz-Marzán, L. M. Surface-Enhanced Raman Scattering Tags for Three-Dimensional Bioimaging and Biomarker Detection. ACS Sens. 2019, 4, 1126– 1137, DOI: 10.1021/acssensors.9b00321109Surface-Enhanced Raman Scattering Tags for Three-Dimensional Bioimaging and Biomarker DetectionLenzi, Elisa; Jimenez de Aberasturi, Dorleta; Liz-Marzan, Luis M.ACS Sensors (2019), 4 (5), 1126-1137CODEN: ASCEFJ; ISSN:2379-3694. (American Chemical Society)A review. The authors have recently witnessed a major improvement in the quality of nanoparticles encoded with Raman-active mols. (SERS tags). Such a progress relied mainly on a major improvement of fabrication methods for building-blocks, resulting in widespread application of this powerful tool in various fields, with the potential to replace commonly used techniques, such as those based on fluorescence. The authors present hereby a brief perspective on SERS tags, regarding their compn., morphol. and structure, and describe the own selection from the current state-of-the-art. The authors then focus on the main bioimaging applications of SERS tags, showing a gradual evolution from two-dimensional studies to three-dimensional anal. Recent improvements in sensitivity and multiplexing ability have enabled great advancements toward in vivo applications, e.g. highlighting tumor boundaries to guide surgery. In addn., the high level of biomol. sensitivity reached by SERS tags, promises an expansion toward biomarker detection in cases for which traditional methods offer limited reliability, as a consequence of the frequently low analyte concns.
- 110Vázquez-Aristizabal, P.; Henriksen-Lacey, M.; García-Astrain, C.; Jimenez de Aberasturi, D.; Langer, J.; Epelde, C.; Litti, L.; Liz-Marzán, L. M.; Izeta, A. Biofabrication and Monitoring of a 3D Printed Skin Model for Melanoma. Adv. Healthc. Mater. 2024, 13, 2401136, DOI: 10.1002/adhm.202401136There is no corresponding record for this reference.
- 111Jimenez de Aberasturi, D.; Serrano-Montes, A. B.; Langer, J.; Henriksen-Lacey, M.; Parak, W. J.; Liz-Marzán, L. M. SERS-Encoded Gold Nanostars for Multiplexed Cell Discrimination. Chem. Mater. 2016, 28, 6779– 6810, DOI: 10.1021/acs.chemmater.6b03349111Surface Enhanced Raman Scattering Encoded Gold Nanostars for Multiplexed Cell DiscriminationJimenez de Aberasturi, Dorleta; Serrano-Montes, Ana B.; Langer, Judith; Henriksen-Lacey, Malou; Parak, Wolfgang J.; Liz-Marzan, Luis M.Chemistry of Materials (2016), 28 (18), 6779-6790CODEN: CMATEX; ISSN:0897-4756. (American Chemical Society)Labeled nanoparticles have attracted much interest toward applications in bioimaging and diagnostics. In particular, surface enhanced Raman scattering (SERS) nanotags have been demonstrated to be excellent candidates for multiplexed imaging and biol. detection. The authors propose an alternative, effective method to easily prep. gold nanostars exhibiting plasmon bands in the near IR range, encoded with Raman reporter mols., concomitantly acting as capping agents which are then protected with an amphiphilic polymer. The resulting nanotags are non-cytotoxic and display long-term stability against aggregation and reporter leakage, while showing reproducible SERS signals suitable for multiplexing. These tags were used to distinguish five different types of breast cancer cells by imaging of a quintuple cell coculture. Time-lapse SERS imaging of the coculture was addnl. performed, demonstrating the applicability of these nanotags for cell tracing over time scales >24 h.
- 112Zhuo, X.; Henriksen-Lacey, M.; Jimenez de Aberasturi, D.; Sánchez-Iglesias, A.; Liz-Marzán, L. M. Shielded Silver Nanorods for Bioapplications. Chem. Mater. 2020, 32, 5879– 5889, DOI: 10.1021/acs.chemmater.0c01995112Shielded Silver Nanorods for BioapplicationsZhuo, Xiaolu; Henriksen-Lacey, Malou; Jimenez de Aberasturi, Dorleta; Sanchez-Iglesias, Ana; Liz-Marzan, Luis M.Chemistry of Materials (2020), 32 (13), 5879-5889CODEN: CMATEX; ISSN:0897-4756. (American Chemical Society)Silver is arguably the best plasmonic material in terms of optical performance. However, wide application of Ag and Ag-contg. nanoparticles is usually hindered by two major drawbacks, namely, chem. degrdn. and cytotoxicity. The authors report herein a synthetic method for highly monodisperse polymer-coated Ag nanorods, which are thereby protected against external stimuli (oxidn., light, heat) and are noncytotoxic to various cell lines. The monodispersity of Ag nanorods endows them with narrow plasmon bands, which are tunable into the near-IR biol. transparency window, thus facilitating application in bioanal. and therapeutic techniques. The authors demonstrate intracellular surface-enhanced Raman scattering (SERS) imaging using Ag nanorods encoded with five different Raman reporter mols. Encoded Ag nanorods display long-term stability in terms of size, shape, optical response, and SERS signal. The authors' results help eliminate concerns of instability and cytotoxicity in the application of Ag-contg. nanoparticles with enhanced optical response, toward the development of bioapplications.
- 113Plou, J.; Molina-Martínez, B.; García-Astrain, C.; Langer, J.; García, I.; Ercilla, A.; Perumal, G.; Carracedo, A.; Liz-Marzán, L. M. Nanocomposite Scaffolds for Monitoring of Drug Diffusion in Three-Dimensional Cell Environments by Surface-Enhanced Raman Spectroscopy. Nano Lett. 2021, 21, 8785– 8793, DOI: 10.1021/acs.nanolett.1c03070113Nanocomposite Scaffolds for Monitoring of Drug Diffusion in Three-Dimensional Cell Environments by Surface-Enhanced Raman SpectroscopyPlou, Javier; Molina-Martinez, Beatriz; Garcia-Astrain, Clara; Langer, Judith; Garcia, Isabel; Ercilla, Amaia; Perumal, Govindaraj; Carracedo, Arkaitz; Liz-Marzan, Luis M.Nano Letters (2021), 21 (20), 8785-8793CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)Monitoring dynamic processes in complex cellular environments requires the integration of uniformly distributed detectors within such three-dimensional (3D) networks, to an extent that the sensor could provide real-time information on nearby perturbations in a non-invasive manner. In this context, the development of 3D-printed structures that can function as both sensors and cell culture platforms emerges as a promising strategy, not only for mimicking a specific cell niche but also toward identifying its characteristic physicochem. conditions, such as concn. gradients. We present herein a 3D cancer model that incorporates a hydrogel-based scaffold contg. gold nanorods. In addn. to sustaining cell growth, the printed nanocomposite inks display the ability to uncover drug diffusion profiles by surface-enhanced Raman scattering, with high spatiotemporal resoln. We addnl. demonstrate that the acquired information could pave the way to designing novel strategies for drug discovery in cancer therapy, through correlation of drug diffusion with cell death.
- 114Aizarna-Lopetegui, U.; García-Astrain, C.; Renero-Lecuna, C.; González-Callejo, P.; Villaluenga, I.; del Pozo, M. A.; Sánchez-Álvarez, M.; Henriksen-Lacey, M.; Jimenez de Aberasturi, D. Remodeling arteries: studying the mechanical properties of 3D-bioprinted hybrid photoresponsive materials. J. Mater. Chem. B 2023, 11, 9431– 9442, DOI: 10.1039/D3TB01480KThere is no corresponding record for this reference.
- 115Zhu, K.; Shin, S. R.; van Kempen, T.; Li, Y. C.; Ponraj, V.; Nasajpour, A.; Mandla, S.; Hu, N.; Liu, X.; Leijten, J.; Lin, Y. D.; Hussain, M. A.; Zhang, Y. S.; Tamayol, A.; Khademhosseini, A. Gold Nanocomposite Bioink for Printing 3D Cardiac Constructs. Adv. Funct Mater. 2017, 27, 1605352, DOI: 10.1002/adfm.201605352There is no corresponding record for this reference.
- 116Alvarez-Puebla, R. A.; Liz-Marzán, L. M. SERS-Based Diagnosis and Biodetection. Small 2010, 6, 604– 610, DOI: 10.1002/smll.200901820116SERS-Based Diagnosis and BiodetectionAlvarez-Puebla, Ramon A.; Liz-Marzan, Luis M.Small (2010), 6 (5), 604-610CODEN: SMALBC; ISSN:1613-6810. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. Surface-enhanced Raman scattering (SERS) spectroscopy is one of the most powerful anal. techniques for identification of mol. species, with the potential to reach single-mol. detection under ambient conditions. This concept article presents a brief introduction and discussion of both recent advances and limitations of SERS in the context of diagnosis and biodetection, ranging from direct sensing to the use of encoded nanoparticles, in particular focusing on ultradetection of relevant bioanalytes, rapid diagnosis of diseases, marking of organelles within individual cells, and non-invasive tagging of anomalous tissues in living animals.
- 117Álvarez-Puebla, R. A.; Liz-Marzán, L. M. Environmental applications of plasmon assisted Raman scattering. Energy Environ. Sci. 2010, 3, 1011– 1017, DOI: 10.1039/c002437f117Environmental applications of plasmon assisted Raman scatteringAlvarez-Puebla, R. A.; Liz-Marzan, L. M.Energy & Environmental Science (2010), 3 (8), 1011-1017CODEN: EESNBY; ISSN:1754-5706. (Royal Society of Chemistry)We present in this review article an overview of the capabilities of surface enhanced Raman scattering (SERS) spectroscopy as a technique for applications related to environmental anal. and monitoring, ranging from the structural characterization of soils, through ultrasensitive detection of pollutants and heavy metal ions, to the anal. of plants, tissues and microorganisms, with a crit. approach in which the drawbacks and difficulties assocd. to the various exptl. configurations and enhancing substrates are introduced, as well as perspectives in the different fields.
- 118Alvarez-Puebla, R. A.; Liz-Marzán, L. M. Traps and cages for universal SERS detection. Chem. Soc. Rev. 2012, 41, 43– 51, DOI: 10.1039/C1CS15155J118Traps and cages for universal SERS detectionAlvarez-Puebla, Ramon A.; Liz-Marzan, Luis M.Chemical Society Reviews (2012), 41 (1), 43-51CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)A review. In this tutorial review, we provide an overview of the recent research toward surface functionalization of plasmonic nanoparticles for the generation of advanced optical sensors that make possible the anal. of various moieties by means of surface enhanced Raman scattering (SERS). Such moieties include at. ions, low affinity target mols., inorg. anions, biometabolites, pathogen markers and/or other analytes of interest even under very demanding circumstances such as those related to real life samples. We expect this review to be of interest to researchers in a broad diversity of fields that can take advantage of the unprecedented sensitivity of this type of mol. spectroscopy, in a wide variety of anal. and bioanal. problems.
- 119Fernández-López, C.; Mateo-Mateo, C.; Álvarez-Puebla, R. A.; Pérez-Juste, J.; Pastoriza-Santos, I.; Liz-Marzán, L. M. Highly Controlled Silica Coating of PEG-Capped Metal Nanoparticles and Preparation of SERS-Encoded Particles. Langmuir 2009, 25, 13894– 13899, DOI: 10.1021/la9016454119Highly Controlled Silica Coating of PEG-Capped Metal Nanoparticles and Preparation of SERS-Encoded ParticlesFernandez-Lopez, Cristina; Mateo-Mateo, Cintia; Alvarez-Puebla, Ramon A.; Perez-Juste, Jorge; Pastoriza-Santos, Isabel; Liz-Marzan, Luis M.Langmuir (2009), 25 (24), 13894-13899CODEN: LANGD5; ISSN:0743-7463. (American Chemical Society)Thiol-modified poly(ethylene glycol) (mPEG-SH) has been used to replace std. capping agents from the surfaces of gold nanoparticles with different sizes and shapes. Upon PEG stabilization, the nanoparticles can be transferred into ethanol, where silica can be directly grown on the particle surfaces through the std. Stober process. The obtained silica shells are uniform and homogeneous, and the method allows a high degree of control over shell thickness for any particle size and shape. Addnl., Raman-active mols. can be readily incorporated within the composite nanoparticles during silica growth so that SERS/SERRS-encoded nanoparticles can be fabricated contg. a variety of tags, thereby envisaging multiplexing capability.
- 120Alvarez-Puebla, R.; Liz-Marzán, L. M.; García de Abajo, F. J. Light Concentration at the Nanometer Scale. J. Phys. Chem. Lett. 2010, 1, 2428– 2434, DOI: 10.1021/jz100820m120Light Concentration at the Nanometer ScaleAlvarez-Puebla, Ramon; Liz-Marzan, Luis M.; Garcia de Abajo, F. JavierJournal of Physical Chemistry Letters (2010), 1 (16), 2428-2434CODEN: JPCLCD; ISSN:1948-7185. (American Chemical Society)Visible and near-IR optical excitations are common currency in the biol. world, and consequently, they are routinely used to study microscopic phenomena taking place in living organisms and their environment. However, the wavelength of light within that energy region is above hundreds of nanometers, thus averting the possibility of direct nanometer-scale resoln. The authors show in this perspective that narrow gaps between metals and sharp tips in colloidal Au particles constitute excellent light confiners that permit solving this problem, and in particular, they lead to record levels of surface-enhanced Raman scattering. The authors' results are framed in the context of a historical quest toward achieving optical focusing in the near field, and the authors offer a tutorial explanation of why evanescent waves such as plasmons are needed for deep-subwavelength focusing. These results provide the required elements of intuition to understand light concn. at the nanometer scale and to design optimized systems for application in ultrasensitive optical analyses and nonlinear photonics.
- 121Becerril-Castro, I. B.; Calderon, I.; Pazos-Perez, N.; Guerrini, L.; Schulz, F.; Feliu, N.; Chakraborty, I.; Giannini, V.; Parak, W. J.; Alvarez-Puebla, R. A. Gold nanostars: Synthesis, optical and SERS analytical properties. Analysis & Sensing 2022, 2, e202200005, DOI: 10.1002/anse.202200022There is no corresponding record for this reference.
- 122Blanco-Formoso, M.; Sousa-Castillo, A.; Xiao, X.; Mariño-Lopez, A.; Turino, M.; Pazos-Perez, N.; Giannini, V.; Correa-Duarte, M. A.; Alvarez-Puebla, R. A. Boosting the analytical properties of gold nanostars by single particle confinement into yolk porous silica shells. Nanoscale 2019, 11, 21872– 21879, DOI: 10.1039/C9NR07889D122Boosting the analytical properties of gold nanostars by single particle confinement into yolk porous silica shellsBlanco-Formoso, Maria; Sousa-Castillo, Ana; Xiao, Xiaofei; Marino-Lopez, Andrea; Turino, Mariacristina; Pazos-Perez, Nicolas; Giannini, Vincenzo; Correa-Duarte, Miguel A.; Alvarez-Puebla, Ramon A.Nanoscale (2019), 11 (45), 21872-21879CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)Herein we illustrate an effective protocol to boost the optical enhancing properties of gold nanostars. By coating single nanostars with a mesoporous silica layer of the appropriate size (yolk capsules), to localize them under optical microscopy, it is possible to enumerate single particles and design SERS quant. methods with minute amts. of metallic particles.
- 123Mariño-Lopez, A.; Sousa-Castillo, A.; Blanco-Formoso, M.; Furini, L. N.; Rodríguez-Lorenzo, L.; Pazos-Perez, N.; Guerrini, L.; Pérez-Lorenzo, M.; Correa-Duarte, M. A.; Alvarez-Puebla, R. A. Microporous Plasmonic Capsules as Stable Molecular Sieves for Direct SERS Quantification of Small Pollutants in Natural Waters. ChemNanoMat 2019, 5, 46– 50, DOI: 10.1002/cnma.201800355123Microporous Plasmonic Capsules as Stable Molecular Sieves for Direct SERS Quantification of Small Pollutants in Natural WatersMarino-Lopez, Andrea; Sousa-Castillo, Ana; Blanco-Formoso, Maria; Furini, Leonardo N.; Rodriguez-Lorenzo, Laura; Pazos-Perez, Nicolas; Guerrini, Luca; Perez-Lorenzo, Moises; Correa-Duarte, Miguel A.; Alvarez-Puebla, Ramon A.ChemNanoMat (2019), 5 (1), 46-50CODEN: CHEMSB; ISSN:2199-692X. (Wiley-VCH Verlag GmbH & Co. KGaA)Fast and versatile optical SERS methods represent a major advance in chem. anal. of environmental samples such as water. To date, however, these ultrasensitive methods are hindered by two key drawbacks: (i) colloidal stability and (ii) chem. diversity, both arising from the compositional complexity of natural samples. Here, we present an engineered material that, due to its unique microporous structure, imparts colloidal stability and provides selectivity while confining a densely populated film of gold nanoparticles optimized for the generation of large electromagnetic fields. The material is tested against natural water for the ultraquantification of dichlorodiphenyl-trichloroethane (DDT), a ubiquitous environmental pollutant.
- 124Sanles-Sobrido, M.; Exner, W.; Rodriguez-Lorenzo, L.; Rodriguez-Gonzalez, B.; Correa-Duarte, M. A.; Alvarez-Puebla, R. A.; Liz-Marzan, L. M. Design of SERS-encoded, submicron, hollow particles through confined growth of encapsulated metal nanoparticles. J. Am. Chem. Soc. 2009, 131, 2699– 2705, DOI: 10.1021/ja8088444124Design of SERS-Encoded, Submicron, Hollow Particles Through Confined Growth of Encapsulated Metal NanoparticlesSanles-Sobrido, Marcos; Exner, Wibke; Rodriguez-Lorenzo, Laura; Rodriguez-Gonzalez, Benito; Correa-Duarte, Miguel A.; Alvarez-Puebla, Ramon A.; Liz-Marzan, Luis M.Journal of the American Chemical Society (2009), 131 (7), 2699-2705CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)The synthetic architectures of complex inorg. nanostructures, including multifunctional hollow capsules, are expected to play key roles in many different applications, such as drug delivery, photonic crystals, nanoreactors, and sensing. Implementation of novel strategies for the fabrication of such materials is needed because of the infancy of this knowledge, which still limits progress in certain areas. Herein the authors report a straightforward synthetic approach for the development of multifunctional submicron reactors comprising catalytic gold nanoparticles (2-3 nm) confined inside hollow silica capsules. Addnl., the confined growth of encapsulated metal nanoparticles was carried out to evidence the usefulness and functionality of these reactors in catalytic applications and as an approach for the development of novel complex nanostructures. Their potential and multifunctionality were pointed out by fabrication of SERS-encoded submicrometer particles with shape and size uniformity for use in antigen biosensing; this was accomplished via codification of gold nanoparticle islands grown onto their inner surfaces.
- 125Riveragil, P.; Vazquez-Vazquez, C.; Giannini, V.; Callao, M. P.; Parak, W. J.; Correa-Duarte, M. A.; Alvarez-Puebla, R. A. Plasmonic nanoprobes for real-time optical monitoring of nitric oxide inside living cells. Angewandte Chemie - International Edition 2013, 52, 13694– 13698, DOI: 10.1002/anie.201306390There is no corresponding record for this reference.
- 126Vázquez-Vázquez, C.; Vaz, B.; Giannini, V.; Pérez-Lorenzo, M.; Alvarez-Puebla, R. A.; Correa-Duarte, M. A. Nanoreactors for simultaneous remote thermal activation and optical monitoring of chemical reactions. J. Am. Chem. Soc. 2013, 135, 13616– 13619, DOI: 10.1021/ja4051873126Nanoreactors for Simultaneous Remote Thermal Activation and Optical Monitoring of Chemical ReactionsVazquez-Vazquez, Carmen; Vaz, Belen; Giannini, Vincenzo; Perez-Lorenzo, Moises; Alvarez-Puebla, Ramon A.; Correa-Duarte, Miguel A.Journal of the American Chemical Society (2013), 135 (37), 13616-13619CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)We report herein the design of plasmonic hollow nanoreactors capable of concg. light at the nanometer scale for the simultaneous performance and optical monitoring of thermally activated reactions. These reactors feature the encapsulation of plasmonic nanoparticles on the inner walls of a mesoporous silica capsule. A Diels-Alder cycloaddn. reaction was carried out in the inner cavities of these nanoreactors to evidence their efficacy. Thus, it is demonstrated that reactions can be accomplished in a confined vol. without alteration of the temp. of the bulk solvent while allowing real-time monitoring of the reaction progress.
- 127Zorlu, T.; Correa-Duarte, M. A.; Alvarez-Puebla, R. A. Composite nanoparticle-metal-organic frameworks for SERS sensing. J. Chem. Phys. 2023, 158, 171001, DOI: 10.1063/5.0144695There is no corresponding record for this reference.
- 128Zorlu, T.; Becerril-Castro, I. B.; Puertolas, B.; Giannini, V.; Correa-Duarte, M. A.; Alvarez-Puebla, R. A. Yolk-Shell Nanostars@Metal Organic Frameworks as Molecular Sieves for Optical Sensing and Catalysis. Angew. Chem., Int. Ed. Engl. 2023, 62, e202305299, DOI: 10.1002/anie.202305299There is no corresponding record for this reference.
- 129Men, D.; Feng, S.; Liu, G.; Hang, L.; Zhang, T. A Sensitive “Optical Nose” for Detection of Volatile Organic Molecules Based on Au@ MOFs Nanoparticle Arrays through Surface-Enhanced Raman Scattering. Particle & Particle Systems Characterization 2020, 37, 1900452, DOI: 10.1002/ppsc.201900452There is no corresponding record for this reference.
- 130Cai, Y.; Wu, Y.; Xuan, T.; Guo, X.; Wen, Y.; Yang, H. Core–shell Au@ metal–organic frameworks for promoting Raman detection sensitivity of methenamine. ACS Appl. Mater. Interfaces 2018, 10, 15412– 15417, DOI: 10.1021/acsami.8b01765130Core-Shell Au@Metal-Organic Frameworks for Promoting Raman Detection Sensitivity of MethenamineCai, Yanzheng; Wu, Yiping; Xuan, Tong; Guo, Xiaoyu; Wen, Ying; Yang, HaifengACS Applied Materials & Interfaces (2018), 10 (18), 15412-15417CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Abuse of methenamine in foodstuff is harmful to the health of people. Routine methods recommended by the national std. are indirect assays with complicated pretreatment of samples or less sensitivity. Core-shell Au nanoparticles@inositol hexaphosphate@MIL-101(Fe) nanoparticles, designated as Au@MIL-101, are successfully synthesized by layer-by-layer assembly. Metal-org. framework (MOF; MIL-101)-modified AuNPs could narrow the distance between neighboring Au@MIL-101, which increases the amt. of hot spots and contributes excellent enhancement of Raman scattering. Certain target mols. could access the proximity to the hot spots by the strong interaction capability of MOF with -COOH groups. Taking the syngeneic effect of hot spots and chem. enhancement via specific binding, Au@MIL-101-based Raman protocol with huge sensitivity is developed to achieve direct detection of methenamine. It has good linearity of dynamic concn. from 3.16 × 10-6 to 1.0 × 10-8 M with correlation coeff. (R2) of 0.9908. The limit of detection reaches 5.0 × 10-10 M. As a practical application, such an Au@MIL-101-based Raman protocol could be used for the direct detn. of trace methenamine in vermicelli, which meets the requirements of the national std.
- 131Shang, W.; Zeng, C.; Du, Y.; Hui, H.; Liang, X.; Chi, C.; Wang, K.; Wang, Z.; Tian, J. Core-shell gold nanorod@ metal-organic framework nanoprobes for multimodality diagnosis of glioma. Advanced Materials (Deerfield Beach, Fla.) 2017, 29, na, DOI: 10.1002/adma.201604381There is no corresponding record for this reference.
- 132Xie, X.; Zhang, Y.; Zhang, L.; Zheng, J.; Huang, Y.; Fa, H. Plasmon-Driven Interfacial Catalytic Reactions in Plasmonic MOF Nanoparticles. Anal. Chem. 2021, 93, 13219– 13225, DOI: 10.1021/acs.analchem.1c02272132Plasmon-Driven Interfacial Catalytic Reactions in Plasmonic MOF NanoparticlesXie, Xin; Zhang, Yaoyao; Zhang, Lingjun; Zheng, Jiangen; Huang, Yingzhou; Fa, HuanbaoAnalytical Chemistry (Washington, DC, United States) (2021), 93 (39), 13219-13225CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Benefiting from the noble metal nanoparticle core and org. porous nanoshell, plasmonic metal-org. frameworks (MOFs) become a nanostructure with great enhancement of the electromagnetic field and a high d. of reaction sites, which has fantastic optical properties in surface plasmon-related fields. In this work, the plasmon-driven interfacial catalytic reactions involving p-aminothiophenol to 4,4'-dimercaptoazobenzene (trans-DMAB) in both the liq. and gaseous phases are studied in plasmonic MOF nanoparticles, which consist of a Ag nanoparticle core and an org. shell (ZIF-8). The surface-enhanced Raman spectroscopy (SERS) spectra recorded at the plasmonic MOF in an aq. environment demonstrate that the reversible plasmon-driven interfacial catalytic reactions could be modulated by a reductant (NaBH4) or oxidant (H2O2). Also, the situ SERS spectra also point out that plasmonic MOF (AgNP@ZIF-8) nanoparticles exhibit much better catalytic performance in the H2O2 soln. compared to pure Ag nanoparticles for the anti-oxidn. caused by the MOF shell. It is surprising that although there is greater SERS enhancement obtained at pure Ag nanoparticles, the plasmon-driven interfacial catalytic reactions only occur at plasmonic AgNP@ZIF-8 nanoparticles in the gaseous phase. This interesting phenomenon is further confirmed and analyzed by simulated electromagnetic field distributions, which could be understood by the effective capture of gaseous mols. by the org. porous nanoshell. Our work not only explores the plasmonic MOF nanoparticles with unique optical properties but also strengthens the understanding of plasmon-driven interfacial catalytic reactions.
- 133Carrillo-Carrión, C.; Martínez, R.; Navarro Poupard, M. F.; Pelaz, B.; Polo, E.; Arenas-Vivo, A.; Olgiati, A.; Taboada, P.; Soliman, M. G.; Catalán, Ú.; Fernández-Castillejo, S.; Solà, R.; Parak, W. J.; Horcajada, P.; Alvarez-Puebla, R. A.; del Pino, P. Aqueous Stable Gold Nanostar/ZIF-8 Nanocomposites for Light-Triggered Release of Active Cargo Inside Living Cells. Angewandte Chemie - International Edition 2019, 58, 7078– 7082, DOI: 10.1002/anie.201902817There is no corresponding record for this reference.
- 134Zorlu, T.; Puértolas, B.; Becerril-Castro, I. B.; Guerrini, L.; Giannini, V.; Correa-Duarte, M. A.; Alvarez-Puebla, R. A. Optical Quantification of Metal Ions Using Plasmonic Nanostructured Microbeads Coated with Metal-Organic Frameworks and Ion-Selective Dyes. ACS Nanoscience Au 2023, 3, 222– 229, DOI: 10.1021/acsnanoscienceau.2c00063There is no corresponding record for this reference.
- 135Zorlu, T.; Becerril-Castro, I. B.; Sousa-Castillo, A.; Puértolas, B.; Besteiro, L. V.; Wang, Z.; Govorov, A.; Correa-Duarte, M. A.; Alvarez-Puebla, R. A. Metal–Organic Frameworks Photocatalyst Through Plasmon-Induced Hot-Electrons. Adv. Funct. Mater. 2024, 34, 2410352, DOI: 10.1002/adfm.202410352There is no corresponding record for this reference.
- 136Huang, C.; Li, A.; Chen, X.; Wang, T. Understanding the Role of Metal–Organic Frameworks in Surface-Enhanced Raman Scattering Application. Small 2020, 16, 2004802, DOI: 10.1002/smll.202004802136Understanding the Role of Metal-Organic Frameworks in Surface-Enhanced Raman Scattering ApplicationHuang, Chuanhui; Li, Ailin; Chen, Xiangyu; Wang, TieSmall (2020), 16 (43), 2004802CODEN: SMALBC; ISSN:1613-6810. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. Metal-org. frameworks (MOFs), built from org. linkers and metal ions/clusters, have emerged as highly promising materials for wide applications. Combining highly porous cryst. MOFs with the surface-enhanced Raman scattering (SERS) technique can achieve unprecedented advantages of high selectivity, high sensitivity, and expedience in anal. and detection. In this crit. review, the aim is to present a comprehensive review of recent advances in understanding of the roles of MOFs in MOF-SERS systems, particularly their structure-to-property correlation. Key examples are selected from representative literature to illustrate crit. concepts and the MOF-based property-dependent applications are particularly emphasized. The barriers, future trends, and prospects for further advances in MOF-SERS platforms are discussed.
- 137Kalaj, M.; Cohen, S. M. Postsynthetic modification: an enabling technology for the advancement of metal–organic frameworks. ACS Central Science 2020, 6, 1046– 1057, DOI: 10.1021/acscentsci.0c00690137Postsynthetic Modification: An Enabling Technology for the Advancement of Metal-Organic FrameworksKalaj, Mark; Cohen, Seth M.ACS Central Science (2020), 6 (7), 1046-1057CODEN: ACSCII; ISSN:2374-7951. (American Chemical Society)A review. Metal-org. frameworks (MOFs) are a class of porous materials with immense chem. tunability derived from their org. and inorg. building blocks. Presynthetic approaches were used to construct tailor-made MOFs, but with a rather restricted functional group scope limited by the typical MOF solvothermal synthesis conditions. Postsynthetic modification (PSM) of MOFs has matured into an alternative strategy to broaden the functional group scope of MOFs. PSM has many incarnations, but 2 main avenues include (1) covalent PSM, in which the org. linkers of the MOF are modified with a reagent resulting in new functional groups, and (2) coordinative PSM, where org. mols. contg. metal ligating groups are introduced onto the inorg. secondary building units (SBUs) of the MOF. These methods have evolved from simple efforts to modifying MOFs to demonstrate proof-of-concept, to becoming key synthetic tools for advancing MOFs for a range of emerging applications, including selective gas sorption, catalysis, and drug delivery. Also, both covalent and coordinative PSM were used to create hierarchal MOFs, MOF-based porous liqs., and other unusual MOF materials. This Outlook highlights recent reports that have extended the scope of PSM in MOFs, some seminal reports that have contributed to the advancement of PSM in MOFs, and view on future directions of the field. The authors highlight recent advances in covalent and coordinative postsynthetic modification of metal-org. frameworks (MOFs) and how these methods have advanced the use of MOFs as functional materials.
- 138Dolgopolova, E. A.; Brandt, A. J.; Ejegbavwo, O. A.; Duke, A. S.; Maddumapatabandi, T. D.; Galhenage, R. P.; Larson, B. W.; Reid, O. G.; Ammal, S. C.; Heyden, A.; Chandrashekhar, M. V. S.; Stavila, V.; Chen, D.; Shustova, N. B. Electronic Properties of Bimetallic Metal–Organic Frameworks (MOFs): Tailoring the Density of Electronic States Through MOF Modularity. J. Am. Chem. Soc. 2017, 139, 5201– 5209, DOI: 10.1021/jacs.7b01125138Electronic Properties of Bimetallic Metal-Organic Frameworks (MOFs): Tailoring the Density of Electronic States through MOF ModularityDolgopolova, Ekaterina A.; Brandt, Amy J.; Ejegbavwo, Otega A.; Duke, Audrey S.; Maddumapatabandi, Thathsara D.; Galhenage, Randima P.; Larson, Bryon W.; Reid, Obadiah G.; Ammal, Salai C.; Heyden, Andreas; Chandrashekhar, Mvs; Stavila, Vitalie; Chen, Donna A.; Shustova, Natalia B.Journal of the American Chemical Society (2017), 139 (14), 5201-5209CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)The development of porous well-defined hybrid materials (e.g., metal-org. frameworks or MOFs) will add a new dimension to a wide no. of applications ranging from supercapacitors and electrodes to smart membranes and thermoelecs. From this perspective, the understanding and tailoring of the electronic properties of MOFs are key fundamental challenges that could unlock the full potential of these materials. The authors focused on the fundamental insights responsible for the electronic properties of three distinct classes of bimetallic systems, Mx-yM'y-MOFs, MxM'y-MOFs, and Mx(ligand-M'y)-MOFs, in which the 2nd metal (M') incorporation occurs through (i) metal (M) replacement in the framework nodes (type I), (ii) metal node extension (type II), and (iii) metal coordination to the org. ligand (type III), resp. The authors employed microwave cond., XPS, diffuse reflectance spectroscopy, powder x-ray diffraction, inductively coupled plasma at. emission spectroscopy, pressed-pellet cond., and theor. modeling to shed light on the key factors responsible for the tunability of MOF electronic structures. Exptl. prescreening of MOFs was performed based on changes in the d. of electronic states near the Fermi edge, which was used as a starting point for further selection of suitable MOFs. As a result, the tailoring of MOF electronic properties could be performed as a function of metal node engineering, framework topol., and/or the presence of unsatd. metal sites while preserving framework porosity and structural integrity. These studies unveil the possible pathways for transforming the electronic properties of MOFs from insulating to semiconducting, as well as provide a blueprint for the development of hybrid porous materials with desirable electronic structures.
- 139Guselnikova, O.; Postnikov, P.; Kolska, Z.; Zaruba, K.; Kohout, M.; Elashnikov, R.; Svorcik, V.; Lyutakov, O. Homochiral metal-organic frameworks functionalized SERS substrate for atto-molar enantio-selective detection. Applied Materials Today 2020, 20, 100666, DOI: 10.1016/j.apmt.2020.100666There is no corresponding record for this reference.
- 140Arabi, M.; Ostovan, A.; Wang, Y.; Mei, R.; Fu, L.; Li, J.; Wang, X.; Chen, L. Chiral molecular imprinting-based SERS detection strategy for absolute enantiomeric discrimination. Nat. Commun. 2022, 13, 5757, DOI: 10.1038/s41467-022-33448-w140Chiral molecular imprinting-based SERS detection strategy for absolute enantiomeric discriminationArabi, Maryam; Ostovan, Abbas; Wang, Yunqing; Mei, Rongchao; Fu, Longwen; Li, Jinhua; Wang, Xiaoyan; Chen, LingxinNature Communications (2022), 13 (1), 5757CODEN: NCAOBW; ISSN:2041-1723. (Nature Portfolio)Chiral discrimination is crit. in environmental and life sciences. However, an ideal chiral discrimination strategy has not yet been developed because of the inevitable nonspecific binding entity of wrong enantiomers or insufficient intrinsic optical activities of chiral mols. Here, we propose an "inspector" recognition mechanism (IRM), which is implemented on a chiral imprinted polydopamine (PDA) layer coated on surface-enhanced Raman scattering (SERS) tag layer. The IRM works based on the permeability change of the imprinted PDA after the chiral recognition and scrutiny of the permeability by an inspector mol. Good enantiomer can specifically recognize and fully fill the chiral imprinted cavities, whereas the wrong cannot. Then a linear shape aminothiol mol., as an inspector of the recognition status is introduced, which can only percolate through the vacant and nonspecifically occupied cavities, inducing the SERS signal to decrease. Accordingly, chirality information exclusively stems from good enantiomer specific binding, while nonspecific recognition of wrong enantiomer is curbed. The IRM benefits from sensitivity and versatility, enabling abs. discrimination of a wide variety of chiral mols. regardless of size, functional groups, polarities, optical activities, Raman scattering, and the no. of chiral centers.
- 141Yang, R.; Zhang, B.; Wang, Y.; Zheng, Y.; Zhang, Q.; Yang, X. Sensitive Determination of Thiram in Apple Samples Using a ZIF-67 Modified Si/Au@Ag Composite as a SERS Substrate. Analytical Methods 2023, 15, 4851– 4861, DOI: 10.1039/D3AY01338CThere is no corresponding record for this reference.
- 142Phan-Quang, G. C.; Han, X.; Koh, C. S. L.; Sim, H. Y. F.; Lay, C. L.; Leong, S. X.; Lee, Y. H.; Pazos-Perez, N.; Alvarez-Puebla, R. A.; Ling, X. Y. Three-Dimensional Surface-Enhanced Raman Scattering Platforms: Large-Scale Plasmonic Hotspots for New Applications in Sensing, Microreaction, and Data Storage. Acc. Chem. Res. 2019, 52, 1844– 1854, DOI: 10.1021/acs.accounts.9b00163142Three-Dimensional Surface-Enhanced Raman Scattering Platforms: Large-Scale Plasmonic Hotspots for New Applications in Sensing, Microreaction, and Data StoragePhan-Quang, Gia Chuong; Han, Xuemei; Koh, Charlynn Sher Lin; Sim, Howard Yi Fan; Lay, Chee Leng; Leong, Shi Xuan; Lee, Yih Hong; Pazos-Perez, Nicolas; Alvarez-Puebla, Ramon A.; Ling, Xing YiAccounts of Chemical Research (2019), 52 (7), 1844-1854CODEN: ACHRE4; ISSN:0001-4842. (American Chemical Society)A review. Surface-enhanced Raman scattering (SERS) is a mol.-specific spectroscopic technique that provides up to 1010-fold enhancement of signature Raman fingerprints using nanometer-scale 0D to 2D platforms. Over the past decades, 3D SERS platforms with addnl. plasmonic materials in the z-axis have been fabricated at sub-micrometer to centimeter scale, achieving higher hotspot d. in all x, y, and z spatial directions and higher tolerance to laser misalignment. Moreover, the flexibility to construct platforms in arbitrary sizes and 3D shapes creates attractive applications besides traditional SERS sensing. In this Account, we introduce our library of substrate-based and substrate-less 3D plasmonic platforms, with an emphasis on their non-sensing applications as microlabs. and data storage labels. We aim to provide a scientific synopsis on these high-potential yet currently overlooked applications of SERS and ignite new scientific discoveries and technol. development in 3D SERS platforms to tackle real-world issues. One highlight of our substrate-based SERS platforms is multilayered platforms built from micrometer-thick assemblies of plasmonic particles, which can achieve up to 1011 enhancement factor. As an alternative, constructing 3D hotspots on non-plasmonic supports significantly reduces waste of plasmonic materials while allowing high flexibility in structural design. We then introduce our emerging substrate-less plasmonic capsules including liq. marbles and colloidosomes, which we further incorporate the latter within an aerosol to form centimeter-scale SERS-active plasmonic cloud, the world's largest 3D SERS platform to date. We then discuss the various emerging applications arising only from these 3D platforms, in the fields of sensing, microreactions, and data storage. An important novel sensing application is the stand-off detection of airborne analytes that are several meters away, made feasible with aerosolized plasmonic clouds. We also describe plasmonic capsules as excellent miniature lab-in-droplets that can simultaneously provide in situ monitoring at the mol. level during reaction, owing to their ultrasensitive 3D plasmonic shells. We highlight the emergence of 3D SERS-based data storage platforms with 10-100-fold higher storage d. than 2D platforms, featuring a new approach in the development of level 3 security (L3S) anti-counterfeiting labels. Ultimately, we recognize that 3D SERS research can only be developed further when its sensing capabilities are concurrently strengthened. With this vision, we foresee the creation of highly applicable 3D SERS platforms that excel in both sensing and non-sensing areas, providing modern solns. in the ongoing Fourth Industrial Revolution.
- 143Phan-Quang, G. C.; Yang, N.; Lee, H. K.; Sim, H. Y. F.; Koh, C. S. L.; Kao, Y. C.; Wong, Z. C.; Tan, E. K. M.; Miao, Y. E.; Fan, W.; Liu, T.; Phang, I. Y.; Ling, X. Y. Tracking Airborne Molecules From Afar: Three-Dimensional Metal–Organic Framework-Surface-Enhanced Raman Scattering Platform for Stand-Off and Real-Time Atmospheric Monitoring. ACS Nano 2019, 13, 12090– 12099, DOI: 10.1021/acsnano.9b06486143Tracking Airborne Molecules from Afar: Three-Dimensional Metal-Organic Framework-Surface-Enhanced Raman Scattering Platform for Stand-Off and Real-Time Atmospheric MonitoringPhan-Quang, Gia Chuong; Yang, Ningchen; Lee, Hiang Kwee; Sim, Howard Yi Fan; Koh, Charlynn Sher Lin; Kao, Ya-Chuan; Wong, Zhao Cai; Tan, Eddie Khay Ming; Miao, Yue-E.; Fan, Wei; Liu, Tianxi; Phang, In Yee; Ling, Xing YiACS Nano (2019), 13 (10), 12090-12099CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Stand-off Raman spectroscopy combines advantages of Raman spectroscopy and remote detection to retrieve mol. vibrational fingerprints of chems. at inaccessible sites. It is currently restricted to detecting pure solids and liqs. and is not widely applicable for dispersed mols. in air. This work used real-time, stand-off SERS spectroscopy for remote, multiplex detection of atm. airborne species by integrating a long-range optic system with a three-dimensional (3D) analyte-sorbing metal-org. framework (MOF)-integrated SERS platform. Formed by the self-assembly of Ag@MOF core-shell nanoparticles, this 3D plasmonic architecture exhibited a micrometer-thick SERS hot-spot to allow active sorption and rapid detection of aerosols, gases, and volatile org. compds. down to parts-per-billion concns., notably up to a 10-m apart distance. The platform is highly sensitive to changes in atm. content, as demonstrated in the temporal monitoring of gaseous CO2 over several cycles. Remote, multiplex quantification of polycyclic arom. hydrocarbon mixts. were demonstrated in real time in outdoor sunlight. By overcoming core challenges in current remote Raman spectroscopy, this strategy creates an opportunity for long-distance, sensitive monitoring of air/gaseous environments at the mol. level, particularly important for environmental conservation, disaster prevention, and homeland defense.
- 144Sun, H.; Cong, S.; Zheng, Z.; Wang, Z.; Chen, Z.; Zhao, Z. Metal–Organic Frameworks as Surface Enhanced Raman Scattering Substrates with High Tailorability. J. Am. Chem. Soc. 2019, 141, 870– 878, DOI: 10.1021/jacs.8b09414144Metal-Organic Frameworks as Surface Enhanced Raman Scattering Substrates with High TailorabilitySun, Hongzhao; Cong, Shan; Zheng, Zuhui; Wang, Zhen; Chen, Zhigang; Zhao, ZhigangJournal of the American Chemical Society (2019), 141 (2), 870-878CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Surface enhanced Raman scattering (SERS) is a widely used anal. technique for detecting trace-level mols. based on an indispensable SERS substrate. SERS substrates with high tailorability are assumed to be attractive and desirable for SERS detection, because the substrates match the need for the selective detection of different species. Nevertheless, the rational design of such SERS substrates is rather challenging for both noble-metal and semiconductor substrates. Herein, expanding beyond conventional SERS substrates, we demonstrate that metal-org. framework (MOF) materials can serve as a type of SERS substrate with mol. selectivity, which are rarely realized for SERS detection without any special pretreatment. A salient structural characteristic of MOF-based SERS substrates benefiting the SERS selectivity is their high tailorability. By controlling the metal centers, org. ligands, and framework topologies of our MOF-based SERS substrates, we show that the electronic band structures of MOF-based SERS substrate can be purposively manipulated to match those of the target analytes, thus resulting in different detectable species. Going further, the SERS enhancement factors (EFs) of the MOF-based SERS substrates can be greatly enhanced to as high as 106 with a low detection limit of 10-8 M by pore-structure optimization and surface modification, which is comparable to the EFs of noble metals without "hot spots" and recently reported semiconductors. This selective enhancement is interpreted as being due to the controllable combination of several resonances, such as the charge-transfer, interband and mol. resonances, together with the ground-state charge-transfer interactions. Our study opens a new venue for the development of SERS substrates with high-design flexibility, which is esp. important for selective SERS detection toward specific analytes.
- 145Alvarez-Puebla, R. A.; Liz-Marzán, L. M. SERS Detection of Small Inorganic Molecules and Ions. Angew. Chem., Int. Ed. 2012, 51, 11214– 11223, DOI: 10.1002/anie.201204438145SERS Detection of Small Inorganic Molecules and IonsAlvarez-Puebla, Ramon A.; Liz-Marzan, Luis M.Angewandte Chemie, International Edition (2012), 51 (45), 11214-11223CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. Surface-enhanced Raman scattering (SERS) is one of the most straightforward applications of the so-called nanoplasmonics. This powerful mol. spectroscopy technique is based on the enhancement of the inelastic scattering from mols. located near nanostructured metallic surfaces when these are illuminated and surface plasmons are excited. The anal. applications of SERS are hindered when the Raman cross-section of the analyte is too low, which is often the case in inorg. mol. species. This problem is even more serious when at. species are to be identified, since these cannot display a vibrational signal. Herein the recent advancements toward the SERS detection of small inorg. compds., including both mol. and at. species are discussed.
- 146Xie, X.; Gao, N.; Huang, Y.; Fang, Y. SERS Monitored Kinetic Process of Gaseous Thiophenol Compound in Plasmonic MOF Nanoparticles. ACS Appl. Mater. Interfaces 2022, 14, 51468– 51475, DOI: 10.1021/acsami.2c13820146SERS Monitored Kinetic Process of Gaseous Thiophenol Compound in Plasmonic MOF NanoparticlesXie, Xin; Gao, Nan; Huang, Yingzhou; Fang, YuruiACS Applied Materials & Interfaces (2022), 14 (45), 51468-51475CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Benefiting from the electromagnetic enhancement of noble metal nanoparticles (NPs) and capture ability of org. frameworks, plasmonic metal-org. frameworks (MOFs) structures have greatly promoted the development of gases detection by surface-enhanced Raman spectroscopy (SERS). In those detections, the kinetic process of gaseous mols. in plasmonic-MOF structures has great influence on SERS spectra, which is still lack of intensive investigation in previous reports. In this work, the kinetic processes of gaseous thiophenol compd. (TPC) in plasmonic Zeolitic Imidazolate Framework (Ag@ZIF) core-shell NPs are studied by SERS spectra. The exptl. data demonstrate the SERS intensities of gaseous TPC could be enhanced once more in a H2 mixed gas environment with different functional group of TPC. Further results reveal that the two-step enhancement of SERS intensities is not only related to the thicknesses of MOF Shell, but also effected by the ambient mixed gas. To understand this novel phenomenon, the binding energy between gaseous mol. and ZIF is calcd. based on first-principle computation. Combining with the plasmonic properties of Ag core, a mol. collision model is introduced here to show the distribution of gaseous TPC mols. in ZIF, which could be responsible for this interesting two-step enhancement of SERS intensities. Furthermore, the H2 assisted kinetic process of gaseous p-aminothiophenol (PATP) is also analyzed by the classical pseudo-first-order kinetic model, which is consistent with our exptl. SERS data. Our work not only reveals the novel phenomenon of plasmonic-MOF structures to improve the gases detection by SERS spectra, but also enriches the understanding the microcosmic process of gaseous mols. in mixed gas environment to optimize MOF structures for gas capture and store.
- 147Ji, W.; Zhao, B.; Ozaki, Y. Semiconductor materials in analytical applications of surface-enhanced Raman scattering. J. Raman Spectrosc. 2016, 47, 51– 58, DOI: 10.1002/jrs.4854147Semiconductor materials in analytical applications of surface-enhanced Raman scatteringJi, Wei; Zhao, Bing; Ozaki, YukihiroJournal of Raman Spectroscopy (2016), 47 (1), 51-58CODEN: JRSPAF; ISSN:0377-0486. (John Wiley & Sons Ltd.)Surface-enhanced Raman scattering (SERS) is increasingly becoming an important anal. technique in various fields, which can mostly be attributed to the significant evolution of SERS-active substrates. The semiconductor-based SERS technique is particularly interesting because the inherent physicochem. properties of semiconductor materials offer several possibilities for the development and improvement of SERS-based anal. techniques. According to the effect of the semiconductor materials in SERS, semiconductor-based SERS techniques can be categorized into two areas: (1) semiconductor-enhanced Raman scattering, in which a semiconductor material is directly used as a substrate for enhancing Raman signals of adsorbed mols., and (2) semiconductor-mediated-enhanced Raman scattering, in which a semiconductor is employed as an 'antenna' or 'trap' to modulate the Raman enhancement originating from a metal substrate. While the theory on semiconductor-based SERS is still incomplete and evolving, semiconductor-based SERS techniques have already resulted in substantial progress in biol. anal., photocatalysis, solar cells, sensing, and optoelectronic devices. The aim of this review is to outline the recent progress in this emerging research field, with a special emphasis on its anal. performance and application areas. Copyright © 2015 John Wiley & Sons, Ltd.
- 148Han, X. X.; Ji, W.; Zhao, B.; Ozaki, Y. Semiconductor-enhanced Raman scattering: active nanomaterials and applications. Nanoscale 2017, 9, 4847– 4861, DOI: 10.1039/C6NR08693D148Semiconductor-enhanced Raman scattering: active nanomaterials and applicationsHan, Xiao Xia; Ji, Wei; Zhao, Bing; Ozaki, YukihiroNanoscale (2017), 9 (15), 4847-4861CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)Surface-enhanced Raman scattering (SERS)-active nanomaterials have extended from noble metals and transition metals to semiconductor materials, since the first discovery of SERS in the mid-1970s. In comparison with metal substrates and transition metals, semiconductor materials have addnl. optical and elec. properties besides SERS enhancement ability, which enable them to display remarkable charge-transfer enhancement and catalytic ability. Moreover, their superior biocompatibility allows these nanomaterials to have great potential applications in bioscience. Herein we highlight the fast growing research field focusing on SERS-active semiconductor nanomaterials and semiconductor-other material heterostructures developed in our group as well as in other related research studies. The material size, morphol. and assembly-dependent SERS enhancement have been discussed in detail. Furthermore, a variety of promising applications of semiconductor-enhanced Raman scattering in photoelec. characterization, redox biochem., sensing, and the catalytic degrdn. of org. pollutants are introduced.
- 149Lombardi, J. R.; Birke, R. L. Theory of Surface-Enhanced Raman Scattering in Semiconductors. J. Phys. Chem. C 2014, 118, 11120– 11130, DOI: 10.1021/jp5020675149Theory of Surface-Enhanced Raman Scattering in SemiconductorsLombardi, John R.; Birke, Ronald L.Journal of Physical Chemistry C (2014), 118 (20), 11120-11130CODEN: JPCCCK; ISSN:1932-7447. (American Chemical Society)An anal. expression was developed for the lowest order nonzero contribution to the SERS from a system composed of a mol. adsorbed on a semiconductor nanoparticle. A combined mol.-semiconductor system and include Herzberg-Teller vibronic coupling of the zero-order Born-Oppenheimer states are considered. This follows a previous derivation for metallic SERS, but instead of a Fermi level, the semiconductor system involves a band gap and the SERS enhancement is maximized at either the conduction or valence band edge. The resulting expression may be regarded as an extension of the Albrecht A-, B-, and C-terms and show that the SERS enhancement is caused by several resonances in the combined system, namely, surface plasmon, exciton, charge-transfer, and mol. resonances. These resonances are coupled by terms in the numerator, which provide strict selection rules that enable one to test the theory and predict the relative intensities of the Raman lines. By considering interactions of the various contributions to the SERS enhancement, ways were developed to optimize the enhancement factor by tailoring the semiconductor nanostructure thereby adjusting the location of the various contributing resonances.
- 150Alessandri, I.; Lombardi, J. R. Enhanced Raman Scattering with Dielectrics. Chem. Rev. 2016, 116, 14921– 14981, DOI: 10.1021/acs.chemrev.6b00365150Enhanced Raman Scattering with DielectricsAlessandri, Ivano; Lombardi, John R.Chemical Reviews (Washington, DC, United States) (2016), 116 (24), 14921-14981CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review. Dielecs. represent a new frontier for surface-enhanced Raman scattering. They can serve as either a complement or an alternative to conventional, metal-based SERS, offering key advantages in terms of low invasiveness, reproducibility, versatility, and recyclability. In comparison to metals, dielec. systems and, in particular, semiconductors are characterized by a much greater variety of parameters and properties that can be tailored to achieve enhanced Raman scattering or related effects. Light-trapping and subwavelength-focusing capabilities, morphol.-dependent resonances, control of band gap and stoichiometry, size-dependent plasmons and excitons, and charge transfer from semiconductors to mols. and vice versa are a few examples of the manifold opportunities assocd. with the use of semiconductors as SERS-active materials. This review provides a broad anal. of SERS with dielecs., encompassing different optical phenomena at the basis of the Raman scattering enhancement and introducing future challenges for light harvesting, vibrational spectroscopy, imaging, and sensing.
- 151Itoh, T.; Procházka, M.; Dong, Z.-C.; Ji, W.; Yamamoto, Y. S.; Zhang, Y.; Ozaki, Y. Toward a New Era of SERS and TERS at the Nanometer Scale: From Fundamentals to Innovative Applications. Chem. Rev. 2023, 123, 1552– 1634, DOI: 10.1021/acs.chemrev.2c00316151Toward a New Era of SERS and TERS at the Nanometer Scale: From Fundamentals to Innovative ApplicationsItoh, Tamitake; Prochazka, Marek; Dong, Zhen-Chao; Ji, Wei; Yamamoto, Yuko S.; Zhang, Yao; Ozaki, YukihiroChemical Reviews (Washington, DC, United States) (2023), 123 (4), 1552-1634CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review. Surface-enhanced Raman scattering (SERS) and tip-enhanced Raman scattering (TERS) have opened a variety of exciting research fields. However, although a vast no. of applications have been proposed since the two techniques were first reported, none has been applied to real practical use. This calls for an update in the recent fundamental and application studies of SERS and TERS. Thus, the goals and scope of this review are to report new directions and perspectives of SERS and TERS, mainly from the viewpoint of combining their mechanism and application studies. Regarding the recent progress in SERS and TERS, this review discusses four main topics: (1) nanometer to subnanometer plasmonic hotspots for SERS; (2) Ångstrom resolved TERS; (3) chem. mechanisms, i.e., charge-transfer mechanism of SERS and semiconductor-enhanced Raman scattering; and (4) the creation of a strong bridge between the mechanism studies and applications.
- 152Lombardi, J. R.; Birke, R. L. A Unified View of Surface-Enhanced Raman Scattering. Acc. Chem. Res. 2009, 42, 734– 742, DOI: 10.1021/ar800249y152A Unified View of Surface-Enhanced Raman ScatteringLombardi, John R.; Birke, Ronald L.Accounts of Chemical Research (2009), 42 (6), 734-742CODEN: ACHRE4; ISSN:0001-4842. (American Chemical Society)A review. In the late 1970s, signal intensity in Raman spectroscopy is enormously enhanced, by a factor of 106 and more recently by ≤1014, when an analyte was placed in the vicinity of a metal nanoparticle (particularly Ag). The underlying source of this huge increase in signal in surface-enhanced Raman scattering (SERS) spectroscopy has since been characterized by considerable controversy. Three possible contributions to the enhancement factor were identified: (i) the surface plasmon resonance in the metal nanoparticle, (ii) a charge-transfer resonance involving transfer of electrons between the mol. and the conduction band of the metal, and (iii) resonances within the mol. itself. These 3 components are often treated as independently contributing to the overall effect, with the implication that by properly choosing the exptl. parameters, ≥1 can be ignored. Although varying exptl. conditions can influence the relative degree to which each resonance influences the total enhancement, higher enhancements can often be obtained by combining ≥2 resonances. Each resonance has a somewhat different effect on the appearance of the resulting Raman spectrum, and it is necessary to invoke ≥1 of these resonances to completely describe a particular expt. However, it is impossible to completely describe all observations of the SERS phenomenon without consideration of all 3 of these contributions. Also, the relative enhancements of individual spectral lines, and therefore the appearance of the spectrum, depend crucially on the exact extent to which each resonance makes a contribution. In this Account, by examg. breakdowns in the Born-Oppenheimer approxn., the authors used Herzberg-Teller coupling to derive a single expression for SERS, which includes contributions from all 3 resonances. Also, these 3 types of resonances are intimately linked by Herzberg-Teller vibronic coupling terms and cannot be considered sep. The authors also examine the differences between SERS and normal Raman spectra. Because of the various resonant contributions, SERS spectra vary with excitation wavelength considerably more than normal Raman spectra. The relative contributions of totally sym. and nontotally sym. lines are also quite different; these differences are due to several effects. The orientation of the mol. with respect to the surface and the inclusion of the metal Fermi level in the list of contributors to the accessible states of the mol.-metal system have a strong influence on the obsd. changes in the Raman spectrum.
- 153Yang, L.; Jiang, X.; Yang, M. Improvement of surface-enhanced Raman scattering performance for broad band gap semiconductor nanomaterial (TiO2): Strategy of metal doping. Appl. Phys. Lett. 2011, 99, 111114, DOI: 10.1063/1.3638467153Improvement of surface-enhanced Raman scattering performance for broad band gap semiconductor nanomaterial (TiO2): Strategy of metal dopingYang, Libin; Jiang, Xin; Yang, MingApplied Physics Letters (2011), 99 (11), 111114/1-111114/3CODEN: APPLAB; ISSN:0003-6951. (American Institute of Physics)The strategy of metal doping was performed to improve surface-enhanced Raman scattering (SERS) performance for semiconductor TiO2 and deeply understand the contributing/controlling factors of semiconductor (TiO2)-to-mol. charge transfer (CT) mechanism contributed to SERS. The amt. and intrinsic nature of doping ions have a great influence on SERS enhancement. An appropriate doping amt. of Fe3+, Co2+, and Ni2+ is 0.5%, 1%, 3% mol., resp., which can enormously improve SERS properties of TiO2 substrate. The considerable SERS enhancement is attributed to doped metal ions, which can embed abundant doping level in TiO2 band gap contributing to semiconductor (TiO2)-to-mol. CT and SERS effect. (c) 2011 American Institute of Physics.
- 154Cong, S.; Yuan, Y.; Chen, Z.; Hou, J.; Yang, M.; Su, Y.; Zhang, Y.; Li, L.; Li, Q.; Geng, F.; Zhao, Z. Noble metal-comparable SERS enhancement from semiconducting metal oxides by making oxygen vacancies. Nat. Commun. 2015, 6, 7800, DOI: 10.1038/ncomms8800154Noble metal-comparable SERS enhancement from semiconducting metal oxides by making oxygen vacanciesCong, Shan; Yuan, Yinyin; Chen, Zhigang; Hou, Junyu; Yang, Mei; Su, Yanli; Zhang, Yongyi; Li, Liang; Li, Qingwen; Geng, Fengxia; Zhao, ZhigangNature Communications (2015), 6 (), 7800CODEN: NCAOBW; ISSN:2041-1723. (Nature Publishing Group)Surface-enhanced Raman spectroscopy (SERS) represents a very powerful tool for the identification of mol. species, but unfortunately it has been essentially restricted to noble metal supports (Au, Ag and Cu). While the application of semiconductor materials as SERS substrate would enormously widen the range of uses for this technique, the detection sensitivity has been much inferior and the achievable SERS enhancement was rather limited, thereby greatly limiting the practical applications. Here, we report the employment of non-stoichiometric tungsten oxide nanostructure, sea urchin-like W18O49 nanowire, as the substrate material, to magnify the substrate-analyte mol. interaction, leading to significant magnifications in Raman spectroscopic signature. The enrichment of surface oxygen vacancy could bring addnl. enhancements. The detection limit concn. was as low as 10-7 M and the max. enhancement factor was 3.4 × 105, in the rank of the highest sensitivity, to our best knowledge, among semiconducting materials, even comparable to noble metals without 'hot spots'.
- 155Liu, H.; Teng, R.; Zhang, S.; Zhao, B.; Ruan, W.; He, D.; Jung, Y. M. Enhancement mechanism of copper ions doped TiO2 substrates based on surface-enhanced raman scattering. Colloids Surf., A 2024, 702, 135152, DOI: 10.1016/j.colsurfa.2024.135152There is no corresponding record for this reference.
- 156Wang, X.; Guo, L. SERS Activity of Semiconductors: Crystalline and Amorphous Nanomaterials. Angew. Chem., Int. Ed. 2020, 59, 4231– 4239, DOI: 10.1002/anie.201913375156SERS Activity of Semiconductors: Crystalline and Amorphous NanomaterialsWang, Xiaotian; Guo, LinAngewandte Chemie, International Edition (2020), 59 (11), 4231-4239CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. Surface-enhanced Raman scattering (SERS) spectroscopy on semiconductors has attracted increasing attention due to its high spectral reproducibility and unique selectively to target mols. Recently, endeavors have been made in fabricating novel SERS-active semiconductor substrates and exploring new enhancement mechanisms to improve the sensitivity of semiconductor substrates. This Minireview explains the enhancement mechanism of the semiconductor SERS effect in a brief tutorial and summarize recent developments of novel semiconductor substrates, in particular with regard to the remarkable SERS activity of amorphous semiconductor nanomaterials. Potential applications of semiconductor SERS are also a key issue of concern. We discuss a variety of promising applications of semiconductor SERS in the fields of in situ anal. chem., spectroelectrochem. anal., biol. sensing, and trace detection.
- 157Livingstone, R.; Zhou, X. C.; Tamargo, M. C.; Lombardi, J. R.; Quagliano, L. C.; Jean-Mary, F. Surface Enhanced Raman Spectroscopy of Pyridine on CdSe/ZnBeSe Quantum Dots Crown by Molecular Beam Epitaxy. J. Phys. Chem. C 2010, 114, 17460– 17464, DOI: 10.1021/jp105619m157Surface Enhanced Raman Spectroscopy of Pyridine on CdSe/ZnBeSe Quantum Dots Grown by Molecular Beam EpitaxyLivingstone, Richard; Zhou, Xuecong; Tamargo, Maria C.; Lombardi, John R.; Quagliano, Lucia G.; Jean-Mary, FleumingueJournal of Physical Chemistry C (2010), 114 (41), 17460-17464CODEN: JPCCCK; ISSN:1932-7447. (American Chemical Society)Using surface enhanced Raman spectroscopy (SERS), the authors obsd. Raman enhancements (104-105) for pyridine mols. adsorbed on II-VI semiconductor quantum dots on (uncapped CdSe/ZnBeSe) produced by MBE. When a monolayer of pyridine is adsorbed on these structures, excitation at 488 nm produces intense Raman spectra, a very large enhancement of the a1, b1, and b2 modes. This indicates charge transfer as a contributor to the enhancement. Also, the excitation wavelength is in the vicinity of several interband transitions located both in the quantum dots and the wetting layer, and probably these resonances also contribute to the enhancement factor.
- 158Yang, L.; Peng, Y.; Yang, Y.; Liu, J.; Huang, H.; Yu, B.; Zhao, J.; Lu, Y.; Huang, Z.; Li, Z.; Lombardi, J. R. A Novel Ultra-Sensitive Semiconductor SERS Substrate Boosted by the Coupled Resonance Effect. Advanced Science 2019, 6, 1900310, DOI: 10.1002/advs.201900310158A Novel Ultra-Sensitive Semiconductor SERS Substrate Boosted by the Coupled Resonance EffectYang Lili; Peng Yusi; Yang Yong; Liu Jianjun; Huang Zhengren; Yang Lili; Peng Yusi; Yang Yong; Yu Bohan; Zhao Jimin; Yang Lili; Peng Yusi; Yang Yong; Huang Haoliang; Lu Yalin; Yu Bohan; Zhao Jimin; Li Zhiyuan; Lombardi John RAdvanced science (Weinheim, Baden-Wurttemberg, Germany) (2019), 6 (12), 1900310 ISSN:2198-3844.Recent achievements in semiconductor surface-enhanced Raman scattering (SERS) substrates have greatly expanded the application of SERS technique in various fields. However, exploring novel ultra-sensitive semiconductor SERS materials is a high-priority task. Here, a new semiconductor SERS-active substrate, Ta2O5, is developed and an important strategy, the "coupled resonance" effect, is presented, to optimize the SERS performance of semiconductor materials by energy band engineering. The optimized Mo-doped Ta2O5 substrate exhibits a remarkable SERS sensitivity with an enhancement factor of 2.2 × 10(7) and a very low detection limit of 9 × 10(-9) m for methyl violet (MV) molecules, demonstrating one of the highest sensitivities among those reported for semiconductor SERS substrates. This remarkable enhancement can be attributed to the synergistic resonance enhancement of three components under 532 nm laser excitation: i) MV molecular resonance, ii) photoinduced charge transfer resonance between MV molecules and Ta2O5 nanorods, and iii) electromagnetic enhancement around the "gap" and "tip" of anisotropic Ta2O5 nanorods. Furthermore, it is discovered that the concomitant photoinduced degradation of the probed molecules in the time-scale of SERS detection is a non-negligible factor that limits the SERS performance of semiconductors with photocatalytic activity.
- 159Jiang, X.; Xu, L.; Ji, W.; Wang, W.; Du, J.; Yang, L.; Song, W.; Han, X.; Zhao, B. One plus one greater than Two: Ultrasensitive Surface-Enhanced Raman scattering by TiO2/ZnO heterojunctions based on Electron-Hole separation. Appl. Surf. Sci. 2022, 584, 152609, DOI: 10.1016/j.apsusc.2022.152609159Ultrasensitive surface-enhanced raman scattering by titanium dioxide/zinc oxide heterojunctions based on electron-hole separationJiang, Xin; Xu, Lin; Ji, Wei; Wang, Weie; Du, Juan; Yang, Libin; Song, Wei; Han, Xiaoxia; Zhao, BingApplied Surface Science (2022), 584 (), 152609CODEN: ASUSEE; ISSN:0169-4332. (Elsevier B.V.)The sepn. of electron-hole pairs has been explored to control the performance of photogenerated carriers in several catalytical and optoelectronic systems, yet its effect on the sensitivity of semiconductor-based surface-enhanced Raman scattering (SERS) is still unknown. Herein, we taken TiO2/ZnO heterojunction as an example to study the role of electron-hole sepn. in semiconductor SERS. The results show that the formation of TiO2/ZnO heterojunction can induce a strong coupling at interface, improving the sepn. of the photogenerated electron-hole pairs. In SERS spectrum, the selective enhancement of non-totally sym. modes (b2) of mol. clearly indicated that the charge-transfer efficiency and SERS-activity can be significantly improved using such a semiconductor-heterojunction. Furthermore, the enhancement factor of 105 was achieved for a non-resonance mol. and the lowest detection concn. can be down to 10-8 M. The findings of this work not only provide a fundamental insight into the role of electron-hole sepn. for semiconductor SERS enhancement, but also open up a novel strategy for design of semiconductor SERS-active substrate with a high charge-transfer contribution.
- 160Zhang, H.; Tang, Y.; Wang, W.; Yu, D.; Yang, L.; Jiang, X.; Song, W.; Zhao, B. A new semiconductor heterojunction SERS substrate for ultra-sensitive detection of antibiotic residues in egg. Food Chem. 2024, 431, 137163, DOI: 10.1016/j.foodchem.2023.137163There is no corresponding record for this reference.
- 161Jiang, X.; He, S.; Tang, Y.; Wang, X.; Zhang, H.; Yang, L.; Kan, W.; Zhao, B. High energy facet-dominated TiO2–X facet heterojunction with excellent carrier utilization for ultrasensitive SERS sensing and efficient degradation of antibiotic residues. Sens. Actuators, B 2024, 403, 135241, DOI: 10.1016/j.snb.2023.135241There is no corresponding record for this reference.
- 162Zhu, L.; Meng, Z.; Zhao, T.; Wang, Y.; Zhao, B. Dye-Sensitized Solar Cells Inspired Method to Modulate Photo-Induced Charge Transfer Efficiency for Enhancing the SERS Activity of Semiconductor. Advanced Materials Interfaces 2023, 2300548, DOI: 10.1002/admi.202300548There is no corresponding record for this reference.
- 163Rodriguez, I.; Shi, L.; Lu, X.; Korgel, B. A.; Alvarez-Puebla, R. A.; Meseguer, F. Silicon nanoparticles as Raman scattering enhancers. Nanoscale 2014, 6, 5666– 5670, DOI: 10.1039/C4NR00593G163Silicon nanoparticles as Raman scattering enhancersRodriguez, I.; Shi, L.; Lu, X.; Korgel, B. A.; Alvarez-Puebla, R. A.; Meseguer, F.Nanoscale (2014), 6 (11), 5666-5670CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)In this communication we demonstrate the large amplification values of the Raman signal of org. mols. attached to silicon nanoparticles (SiNPs). Light induced Mie resonances of high refractive index particles generate strong evanescent electromagnetic (EM) fields, thus boosting the Raman signal of species attached to the nanoparticles. The interest of this process is justified by the wide range of exptl. configurations that can be implemented including photonic crystals, the sharp spectral resonances easily tuneable with the particle size, the biocompatibility and biodegradability of silicon, and the possibility of direct anal. of mols. that do not contain functional groups with high affinity for gold and silver. Addnl., silicon nanoparticles present stronger field enhancement due to Mie resonances at larger sizes than gold.
- 164Öner, I. H.; Querebillo, C. J.; David, C.; Gernert, U.; Walter, C.; Driess, M.; Leimkühler, S.; Ly, K. H.; Weidinger, I. M. High Electromagnetic Field Enhancement of TiO2 Nanotube Electrodes. Angew. Chem., Int. Ed. 2018, 57, 7225– 7229, DOI: 10.1002/anie.201802597164High Electromagnetic Field Enhancement of TiO2 Nanotube ElectrodesOner Ibrahim Halil; Weidinger Inez M; Querebillo Christine Joy; Walter Carsten; Driess Matthias; David Christin; Gernert Ulrich; Leimkuhler Silke; Ly Khoa HoangAngewandte Chemie (International ed. in English) (2018), 57 (24), 7225-7229 ISSN:.We present the fabrication of TiO2 nanotube electrodes with high biocompatibility and extraordinary spectroscopic properties. Intense surface-enhanced resonance Raman signals of the heme unit of the redox enzyme Cytochrome b5 were observed upon covalent immobilization of the protein matrix on the TiO2 surface, revealing overall preserved structural integrity and redox behavior. The enhancement factor could be rationally controlled by varying the electrode annealing temperature, reaching a record maximum value of over 70 at 475 °C. For the first time, such high values are reported for non-directly surface-interacting probes, for which the involvement of charge-transfer processes in signal amplification can be excluded. The origin of the surface enhancement is exclusively attributed to enhanced localized electric fields resulting from the specific optical properties of the nanotubular geometry of the electrode.
- 165Han, X. X.; Köhler, C.; Kozuch, J.; Kuhlmann, U.; Paasche, L.; Sivanesan, A.; Weidinger, I. M.; Hildebrandt, P. Potential-Dependent Surface-Enhanced Resonance Raman Spectroscopy at Nanostructured TiO2: A Case Study on Cytochrome b5. Small 2013, 9, 4175– 4181, DOI: 10.1002/smll.201301070165Potential-Dependent Surface-Enhanced Resonance Raman Spectroscopy at Nanostructured TiO2: A Case Study on Cytochrome b5Han, Xiao Xia; Koehler, Christopher; Kozuch, Jacek; Kuhlmann, Uwe; Paasche, Lars; Sivanesan, Arumugam; Weidinger, Inez M.; Hildebrandt, PeterSmall (2013), 9 (24), 4175-4181CODEN: SMALBC; ISSN:1613-6810. (Wiley-VCH Verlag GmbH & Co. KGaA)Nanostructured titanium dioxide (TiO2) electrodes, prepd. by anodization of titanium, are employed to probe the electron-transfer process of cytochrome b5 (cyt b5) by surface-enhanced resonance Raman (SERR) spectroscopy. Concomitant with the increased nanoscopic surface roughness of TiO2, achieved by raising the anodization voltage from 10 to 20 V, the enhancement factor increases from 2.4 to 8.6, which is rationalized by calcns. of the elec. field enhancement. Cyt b5 is immobilized on TiO2 under preservation of its native structure but it displays a non-ideal redox behavior due to the limited cond. of the electrode material. The electron-transfer efficiency which depends on the cryst. phase of TiO2 has to be improved by appropriate doping for applications in bioelectrochem.
- 166Alessandri, I. Enhancing Raman Scattering without Plasmons: Unprecedented Sensitivity Achieved by TiO2 Shell-Based Resonators. J. Am. Chem. Soc. 2013, 135, 5541– 5544, DOI: 10.1021/ja401666p166Enhancing Raman Scattering without Plasmons: Unprecedented Sensitivity Achieved by TiO2 Shell-Based ResonatorsAlessandri, IvanoJournal of the American Chemical Society (2013), 135 (15), 5541-5544CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)A remarkable enhancement of Raman scattering is achieved by TiO2 shell-based spherical resonators in the absence of plasmonic enhancers. This effect is ascribed to the synergistic combination of high refractive index of the shell layer, multiple light scattering through the spheres, and related geometrical factors and can be exploited to fabricate a new generation of self-diagnostic, recyclable SERS-active substrates.
- 167Qi, D.; Lu, L.; Wang, L.; Zhang, J. Improved SERS Sensitivity on Plasmon-Free TiO2 Photonic Microarray by Enhancing Light-Matter Coupling. J. Am. Chem. Soc. 2014, 136, 9886– 9889, DOI: 10.1021/ja5052632167Improved SERS Sensitivity on Plasmon-Free TiO2 Photonic Microarray by Enhancing Light-Matter CouplingQi, Dianyu; Lu, Liujia; Wang, Lingzhi; Zhang, JinlongJournal of the American Chemical Society (2014), 136 (28), 9886-9889CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Highly sensitive surface-enhanced Raman scattering (SERS) detection was achieved on plasmon-free TiO2 photonic artificial microarray, which can be quickly recovered under simulated solar light irradn. and repeatedly used. The sensitive detection performance is attributed to the enhanced matter-light interaction through repeated and multiple light scattering in photonic microarray. The SERS sensitivity is unprecedentedly found to be dependent on the different light-coupling performance of microarray with various photonic band gaps, where microarray with band gap center near to laser wavelength shows a lower SERS signal due to depressed light propagation, while those with band gap edges near to laser wavelength show higher sensitivity due to slow light effect.
- 168Ji, W.; Li, L.; Song, W.; Wang, X.; Zhao, B.; Ozaki, Y. Enhanced Raman Scattering by ZnO Superstructures: Synergistic Effect of Charge Transfer and Mie Resonances. Angew. Chem., Int. Ed. 2019, 58, 14452– 14456, DOI: 10.1002/anie.201907283168Enhanced Raman Scattering by ZnO Superstructures: Synergistic Effect of Charge Transfer and Mie ResonancesJi, Wei; Li, Linfang; Song, Wei; Wang, Xinnan; Zhao, Bing; Ozaki, YukihiroAngewandte Chemie, International Edition (2019), 58 (41), 14452-14456CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)A remarkable enhancement of Raman scattering is achieved by sub-μm-sized spherical ZnO superstructures. The secondary superstructures of ZnO particles with a uniform diam. at 220-490 nm was formed by aggregating ∼13 nm primary single crystallites. By engineering the superstructure size to induce Mie resonances, leading to an electromagnetic contribution to the SERS enhancement. A highly efficient charge-transfer (CT) contribution derived from the primary structure of the ZnO nanocrystallites was able to enhance the SERS signals as well. The highest Raman enhancement factor of 105 was achieved for a nonresonant mol. by the synergistic effect of CT and Mie resonances. The Mie resonances scattered near-field effect studied in the present study provides not only an important guide for designing novel SERS-active semiconductor substrates, but also a coherent framework for modeling the electromagnetic mechanism of SERS on semiconductors.
- 169Liu, X.; Ye, Z.; Xiang, Q.; Xu, Z.; Yue, W.; Li, C.; Xu, Y.; Wang, L.; Cao, X.; Zhang, J. Boosting electromagnetic enhancement for detection of non-adsorbing analytes on semiconductor SERS substrates. Chem. 2023, 9, 1464– 1476, DOI: 10.1016/j.chempr.2023.01.017There is no corresponding record for this reference.
- 170Ji, W.; Li, L.; Guan, J.; Mu, M.; Song, W.; Sun, L.; Zhao, B.; Ozaki, Y. Hollow Multi-Shelled V2O5 Microstructures Integrating Multiple Synergistic Resonances for Enhanced Semiconductor SERS. Advanced Optical Materials 2021, 9, 2101866, DOI: 10.1002/adom.202101866There is no corresponding record for this reference.
- 171Li, J.; Xie, Q.; Li, J.; Sun, L.; Xie, Y.; Ozaki, Y.; Ji, W. Macroscale TiO2 Microspherical Arrays with Multiple Synergistic Effect for Highly Sensitive Surface-Enhanced Raman Scattering. Adv. Funct. Mater. 2024, 34, 2400523, DOI: 10.1002/adfm.202400523There is no corresponding record for this reference.
- 172Mu, M.; Wen, S.; Hu, S.; Zhao, B.; Song, W. Putting surface-enhanced Raman spectroscopy to work for nanozyme research: Methods, materials and applications. TrAC Trends in Analytical Chemistry 2022, 152, 116603, DOI: 10.1016/j.trac.2022.116603There is no corresponding record for this reference.
- 173Zhang, Y.; Yang, T.; Li, J.; Zhang, Q.; Li, B.; Gao, M. Construction of Ru, O Co-Doping MoS2 for Hydrogen Evolution Reaction Electrocatalyst and Surface-Enhanced Raman Scattering Substrate: High-Performance, Recyclable, and Durability Improvement. Adv. Funct. Mater. 2023, 33, 2210939, DOI: 10.1002/adfm.202210939There is no corresponding record for this reference.
- 174Zheng, X.; Ye, Z.; Akmal, Z.; He, C.; Zhang, J.; Wang, L. Recent progress in SERS monitoring of photocatalytic reactions. Chem. Soc. Rev. 2024, 53, 656– 683, DOI: 10.1039/D3CS00462GThere is no corresponding record for this reference.
- 175Fan, K. L.; Gao, L. Z.; Wei, H.; Jiang, B.; Wang, D. J.; Zhang, R. F.; He, J. Y.; Meng, X. Q.; Wang, Z. R.; Fan, H. Z.; Wen, T.; Duan, D. M.; Chen, L.; Jiang, W.; Lu, Y.; Jiang, B.; Wei, Y. H.; Li, W.; Yuan, Y.; Dong, H. J.; Zhang, L.; Hong, C. Y.; Zhang, Z. X.; Cheng, M. M.; Geng, X.; Hou, T. Y.; Hou, Y. X.; Li, J. R.; Tang, G. H.; Zhao, Y.; Zhao, H. Q.; Zhang, S.; Xie, J. Y.; Zhou, Z. J.; Ren, J. S.; Huang, X. L.; Gao, X. F.; Liang, M. M.; Zhang, Y.; Xu, H. Y.; Qu, X. G.; Yan, X. Y. Nanozymes. Progress in Chemistry 2023, 35, 1– 87, DOI: 10.7536/PC220833There is no corresponding record for this reference.
- 176Jin, J.; Song, W.; Wang, J. Q.; Li, L. J.; Tian, Y.; Zhu, S. J.; Zhang, Y. P.; Xu, S. P.; Yang, B.; Zhao, B. A highly sensitive SERS platform based on small-sized Ag/GQDs nanozyme for intracellular analysis. Chemical Engineering Journal 2022, 430, 132687, DOI: 10.1016/j.cej.2021.132687There is no corresponding record for this reference.
- 177Zhao, Q. N.; Cheng, X. H.; Hu, S. Z.; Zhao, M. H.; Chen, J. J.; Mu, M.; Yang, Y. M.; Liu, H.; Hu, L. H.; Zhao, B.; Song, W. Bilateral efforts to improve SERS detection efficiency of exosomes by Au/ Na7PMo11O39 Combined with Phospholipid Epitope Imprinting. Biosens. Bioelectron. 2024, 258, 116349, DOI: 10.1016/j.bios.2024.116349There is no corresponding record for this reference.
- 178Wen, S. S.; Ma, X. W.; Liu, H.; Chen, G.; Wang, H.; Deng, G. Q.; Zhang, Y. T.; Song, W.; Zhao, B.; Ozaki, Y. Accurate Monitoring Platform for the Surface Catalysis of Nanozyme Validated by Surface-Enhanced Raman-Kinetics Model. Anal. Chem. 2020, 92, 11763– 11770, DOI: 10.1021/acs.analchem.0c01886178Accurate Monitoring Platform for the Surface Catalysis of Nanozyme Validated by Surface-Enhanced Raman-Kinetics ModelWen, Sisi; Ma, Xiaowei; Liu, Hao; Chen, Gang; Wang, He; Deng, Gaoqiang; Zhang, Yuantao; Song, Wei; Zhao, Bing; Ozaki, YukihiroAnalytical Chemistry (Washington, DC, United States) (2020), 92 (17), 11763-11770CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Surface-enhanced Raman scattering (SERS) is a supersensitive technique for monitoring catalytic reactions. However, building a SERS-kinetics model to study catalytic efficiency on the surface or interface of the catalyst remains a great challenge. The authors successfully obtained an excellent semiconducting SERS substrate, reduced MnCo2O4 (R-MnCo2O4) nanotubes, whose favorable SERS sensitivity is mainly related to the promoted interfacial charge transfer caused by the introduction of oxygen vacancies as well as the electromagnetic enhancement effect. Also, the R-MnCo2O4 nanotubes showed a favorable oxidase-like activity toward oxidn. with the aid of O2. It was also showed the oxidase-like catalytic process could be monitored using the SERS technique. A new SERS-kinetics model to monitor the catalytic efficiency of the oxidase-like reaction was developed, and the Vm values measured by the SERS-kinetics method are close to that obtained by the UV-visible approach, while the Km values measured by the SERS-kinetics method are much lower, demonstrating the better affinity between the enzyme and the substrate from SERS results and further confirming the high sensitivity of the SERS-kinetics approach and the actual enzyme-like reaction on the surface of nanozymes, which provides guidance in understanding the kinetics process and catalytic mechanism of natural enzymic and other artificial enzymic reactions. This work demonstrated the improved SERS sensitivity of defective semiconductors for the application of enzyme mimicking, providing a new frontier to construct highly sensitive biosensors.
- 179Wen, S. S.; Jiang, W. J.; Yang, Y. M.; Shang, L. J.; Wang, X.; Zhao, B.; Song, W. Research on Surface-Enhanced Raman Spectroscopy and Simulated Laccase Activity of Two-Dimensional Metal Sulfide Nanosheets. J. Phys. Chem. C 2024, 128, 4224– 4232, DOI: 10.1021/acs.jpcc.4c00844There is no corresponding record for this reference.
- 180Huang, L. J.; Sun, D. W.; Pu, H. B.; Wei, Q. Y.; Luo, L. P.; Wang, J. L. A colorimetric paper sensor based on the domino reaction of acetylcholinesterase and degradable γ-MnOOH nanozyme for sensitive detection of organophosphorus pesticides. Sensors and Actuators B-Chemical 2019, 290, 573– 580, DOI: 10.1016/j.snb.2019.04.020There is no corresponding record for this reference.
- 181Xi, H. Y.; Gu, H. F.; Han, Y. R.; You, T. T.; Wu, P. F.; Liu, Q. Q.; Zheng, L. R.; Liu, S. H.; Fu, Q.; Chen, W. X.; Gao, Y. K.; Wang, Y. T.; Yin, P. G. Peroxidase-like single Fe atoms anchored on Ti3C2Tx MXene as surface enhanced Raman scattering substrate for the simultaneous discrimination of multiple antioxidants. Nano Research 2023, 16, 10053– 10060, DOI: 10.1007/s12274-023-5739-2There is no corresponding record for this reference.
- 182Chen, Y.; Zhang, J.; Li, J. Y.; Hu, Y. L.; Ge, K.; Li, G. K.; Liu, S. C. Bifunctional Mo2N Nanoparticles with Nanozyme and SERS Activity: A Versatile Platform for Sensitive Detection of Biomarkers in Serum Samples. Anal. Chem. 2024, 96, 2998– 3007, DOI: 10.1021/acs.analchem.3c04801There is no corresponding record for this reference.
- 183Yang, Y.; Wang, C.; Wang, N.; Li, J.; Zhu, Y.; Zai, J.; Fu, J.; Hao, Y. Photogenerated reactive oxygen species and hyperthermia by Cu3SnS4 nanoflakes for advanced photocatalytic and photothermal antibacterial therapy. J. Nanobiotechnol. 2022, 20, 195, DOI: 10.1186/s12951-022-01403-yThere is no corresponding record for this reference.
- 184Lin, L.; Bi, X.; Gu, Y.; Wang, F.; Ye, J. Surface-enhanced Raman scattering nanotags for bioimaging. J. Appl. Phys. 2021, 129, 191101, DOI: 10.1063/5.0047578184Surface-enhanced Raman scattering nanotags for bioimagingLin, Li; Bi, Xinyuan; Gu, Yuqing; Wang, Fu; Ye, JianJournal of Applied Physics (Melville, NY, United States) (2021), 129 (19), 191101CODEN: JAPIAU; ISSN:0021-8979. (American Institute of Physics)A review. Surface-enhanced Raman scattering (SERS) technique has shown extraordinary features for biomedical applications. The implementation of SERS nanotags has opened a new era for bioimaging and detections. As a powerful tool, SERS nanotags provide favorable properties such as fingerprint spectrum, narrow peak linewidth, good photostability, and high spatial resoln. accompanied by various rational designs of nanoparticles. They have proven as useful imaging agents for in vivo, ex vivo, and in vitro detection of cancerous cells and tissues. This tutorial provides the basic principles of SERS and SERS nanotags, including recent progress of SERS-based bioimaging applications, as well as the outlooks into the future developments toward practical clin. SERS. (c) 2021 American Institute of Physics.
- 185Jin, X.; He, J.; Ye, J. Nanotriangle-based gap-enhanced Raman tags for bioimaging and photothermal therapy. J. Appl. Phys. 2019, 125, 073102, DOI: 10.1063/1.5081891185Nanotriangle-based gap-enhanced Raman tags for bioimaging and photothermal therapyJin, Xiulong; He, Jing; Ye, JianJournal of Applied Physics (Melville, NY, United States) (2019), 125 (7), 073102/1-073102/11CODEN: JAPIAU; ISSN:0021-8979. (American Institute of Physics)Surface-enhanced Raman scattering (SERS) nanoparticles can be utilized as optical labeling nanoprobes for bioimaging with advantages of the fingerprint vibrational signal as a unique optical code and the ultra-narrow linewidth for multiplexing. As a new type of SERS nanoprobes, gap-enhanced Raman tags (GERTs) developed recently can overcome the common issues of poor photostability and limited Raman enhancement. In this work, we have constructed bright nanotriangle-based GERTs (NT-GERTs) for combined SERS bioimaging and photothermal therapy. With optimized Au shell morphol. and thickness, NT-GERTs possess 20 folds brighter SERS signal and a more efficient photothermal effect compared to conventional nanosphere-based GERTs. These NT-GERTs show great potential for intraoperative SERS bioimaging guided photothermal therapy of cancers. (c) 2019 American Institute of Physics.
- 186Gurav, D. D.; Jia, Y. A.; Ye, J.; Qian, K. Design of plasmonic nanomaterials for diagnostic spectrometry. Nanoscale Advances 2019, 1, 459– 469, DOI: 10.1039/C8NA00319JThere is no corresponding record for this reference.
- 187Gu, Y.; Bi, X.; Ye, J. Gap-enhanced resonance Raman tags for live-cell imaging. J. Mater. Chem. B 2020, 8, 6944– 6955, DOI: 10.1039/D0TB00659A187Gap-enhanced resonance Raman tags for live-cell imagingGu, Yuqing; Bi, Xinyuan; Ye, JianJournal of Materials Chemistry B: Materials for Biology and Medicine (2020), 8 (31), 6944-6955CODEN: JMCBDV; ISSN:2050-7518. (Royal Society of Chemistry)Surface-enhanced Raman scattering (SERS) nanotags are widely used in the biomedical field including live-cell imaging due to the high specificity from their fingerprint spectrum and the multiplexing capability from the ultra-narrow linewidth. However, long-term live-cell Raman imaging is limited due to the photodamage from a relatively long exposure time and a high laser power, which are needed for acquiring detectable Raman signals. The authors attempt to resolve this issue by developing ultrabright gap-enhanced resonance Raman tags (GERRTs), consisting of a petal-like gold core and a silver shell with the near-IR resonant reporter of IR-780 embedded in between, for long-term and high-speed live-cell imaging. GERRTs exhibit an ultrahigh Raman intensity down to a single-nanoparticle level in aq. soln. and the solid state upon 785 nm excitation, allowing for high-resoln. time-lapse live-cell Raman imaging with an exposure time of 1 ms per pixel and a laser power of 50μW. Under these measurement conditions, the authors can possibly capture dynamic cellular processes with a high temporal resoln., and track living cells for long periods of time owing to the reduced photodamage to cells. These nanotags open new opportunities for ultrasensitive, low-phototoxic, and long-term live-cell imaging.
- 188Liu, H.; Gao, X.; Xu, C.; Liu, D. SERS Tags for Biomedical Detection and Bioimaging. Theranostics 2022, 12, 1870– 1903, DOI: 10.7150/thno.66859188SERS tags for biomedical detection and bioimagingLiu, Huiqiao; Gao, Xia; Xu, Chen; Liu, DingbinTheranostics (2022), 12 (4), 1870-1903CODEN: THERDS; ISSN:1838-7640. (Ivyspring International Publisher)A review. Surface-enhanced Raman scattering (SERS) has emerged as a valuable technique for mol. identification. Due to the characteristics of high sensitivity, excellent signal specificity, and photobleaching resistance, SERS has been widely used in the fields of environmental monitoring, food safety, and disease diagnosis. By attaching the org. mols. to the surface of plasmonic nanoparticles, the obtained SERS tags show high-performance multiplexing capability for biosensing. The past decade has witnessed the progress of SERS tags for liq. biopsy, bioimaging, and theranostics applications. This review focuses on the advances of SERS tags in biomedical fields. We first introduce the building blocks of SERS tags, followed by the summarization of recent progress in SERS tags employed for detecting biomarkers, such as DNA, miRNA, and protein in biol. fluids, as well as imaging from in vitro cell, bacteria, tissue to in vivo tumors. Further, we illustrate the appealing applications of SERS tags for delineating tumor margins and cancer diagnosis. In the end, perspectives of SERS tags projecting into the possible obstacles are deliberately proposed in future clin. translation.
- 189Zhang, Y.; Gu, H.; Wu, Z.; Ye, J.; Lin, L. L. Nanoengineering for gap-enhanced Raman tags and related plasmonic applications. Ramamurthy, S. S.; Bhaskar, S.; Reddy, N., Eds.; In Micro and Nano Technologies, Nano-Engineering at Functional Interfaces for Multi-Disciplinary Applications; Elsevier: 2025; pp 75– 91, https://doi.org/10.1016/B978-0-443-21691-6.00005-6.There is no corresponding record for this reference.
- 190Lim, D.-K.; Jeon, K.-S.; Hwang, J.-H.; Kim, H.; Kwon, S.; Suh, Y. D.; Nam, J.-M. Highly uniform and reproducible surface-enhanced Raman scattering from DNA-tailorable nanoparticles with 1-nm interior gap. Nat. Nanotechnol. 2011, 6, 452– 460, DOI: 10.1038/nnano.2011.79190Highly uniform and reproducible surface-enhanced Raman scattering from DNA-tailorable nanoparticles with 1-nm interior gapLim, Dong-Kwon; Jeon, Ki-Seok; Hwang, Jae-Ho; Kim, Hyoki; Kwon, Sunghoon; Suh, Yung Doug; Nam, Jwa-MinNature Nanotechnology (2011), 6 (7), 452-460CODEN: NNAABX; ISSN:1748-3387. (Nature Publishing Group)An ideal surface-enhanced Raman scattering (SERS) nanostructure for sensing and imaging applications should induce a high signal enhancement, generate a reproducible and uniform response, and should be easy to synthesize. Many SERS-active nanostructures have been investigated, but they suffer from poor reproducibility of the SERS-active sites, and the wide distribution of their enhancement factor values results in an unquantifiable SERS signal. Here, we show that DNA on gold nanoparticles facilitates the formation of well-defined gold nanobridged nanogap particles (Au-NNP) that generate a highly stable and reproducible SERS signal. The uniform and hollow gap (∼1 nm) between the gold core and gold shell can be precisely loaded with a quantifiable amt. of Raman dyes. SERS signals generated by Au-NNPs showed a linear dependence on probe concn. (R2 > 0.98) and were sensitive down to 10fM concns. Single-particle nano-Raman mapping anal. revealed that >90% of Au-NNPs had enhancement factors greater than 1.0 × 108, which is sufficient for single-mol. detection, and the values were narrowly distributed between 1.0 × 108 and 5.0 × 109.
- 191Zhang, Y.; Gu, Y.; He, J.; Thackray, B. D.; Ye, J. Ultrabright gap-enhanced Raman tags for high-speed bioimaging. Nat. Commun. 2019, 10, 3905, DOI: 10.1038/s41467-019-11829-y191Ultrabright gap-enhanced Raman tags for high-speed bioimagingZhang Yuqing; Gu Yuqing; He Jing; Thackray Benjamin D; Ye Jian; Zhang Yuqing; Ye Jian; Ye JianNature communications (2019), 10 (1), 3905 ISSN:.Surface-enhanced Raman spectroscopy (SERS) is advantageous over fluorescence for bioimaging due to ultra-narrow linewidth of the fingerprint spectrum and weak photo-bleaching effect. However, the existing SERS imaging speed lags far behind practical needs, mainly limited by Raman signals of SERS nanoprobes. In this work, we report ultrabright gap-enhanced Raman tags (GERTs) with strong electromagnetic hot spots from interior sub-nanometer gaps and external petal-like shell structures, larger immobilization surface area, and Raman cross section of reporter molecules. These GERTs reach a Raman enhancement factor beyond 5 × 10(9) and a detection sensitivity down to a single-nanoparticle level. We use a 370 μW laser to realize high-resolution cell imaging within 6 s and high-contrast (a signal-to-background ratio of 80) wide-area (3.2 × 2.8 cm(2)) sentinel lymph node imaging within 52 s. These nanoprobes offer a potential solution to overcome the current bottleneck in the field of SERS-based bioimaging.
- 192Lin, L.; Gu, H.; Ye, J. Plasmonic multi-shell nanomatryoshka particles as highly tunable SERS tags with built-in reporters. Chem. Commun. (Camb) 2015, 51, 17740– 3, DOI: 10.1039/C5CC06599B192Plasmonic multi-shell nanomatryoshka particles as highly tunable SERS tags with built-in reportersLin, Li; Gu, Hongchen; Ye, JianChemical Communications (Cambridge, United Kingdom) (2015), 51 (100), 17740-17743CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)The synthesis and averaged SERS measurements of multi-shell nanomatryoshka SERS tags are reported. By tuning the no. of shells or by changing the Raman reporters in different gap layers, their Raman intensities and spectral bands were tunable. These tags show great potential for SERS-based biosensing and bioimaging.
- 193Gu, Y.; He, C.; Liu, F.; Ye, J. Raman ink for steganography. Advanced Optical Materials 2021, 9, 2002038, DOI: 10.1002/adom.202002038There is no corresponding record for this reference.
- 194Gu, Y.; He, C.; Zhang, Y.; Lin, L.; Thackray, B. D.; Ye, J. Gap-enhanced Raman tags for physically unclonable anticounterfeiting labels. Nat. Commun. 2020, 11, 516, DOI: 10.1038/s41467-019-14070-9194Gap-enhanced Raman tags for physically unclonable anticounterfeiting labelsGu, Yuqing; He, Chang; Zhang, Yuqing; Lin, Li; Thackray, Benjamin David; Ye, JianNature Communications (2020), 11 (1), 516CODEN: NCAOBW; ISSN:2041-1723. (Nature Research)Abstr.: Anticounterfeiting labels based on phys. unclonable functions (PUFs), as one of the powerful tools against counterfeiting, are easy to generate but difficult to duplicate due to inherent randomness. Gap-enhanced Raman tags (GERTs) with embedded Raman reporters show strong intensity enhancement and ultra-high photostability suitable for fast and repeated readout of PUF labels. Herein, we demonstrate a PUF label fabricated by drop-casting aq. GERTs, high-speed read using a confocal Raman system, digitized through coarse-grained coding methods, and authenticated via pixel-by-pixel comparison. A three-dimensional encoding capacity of over 3 × 1015051 can be achieved for the labels composed of ten types of GERTs with a mapping resoln. of 2500 pixels and quaternary encoding of Raman intensity levels at each pixel. Authentication expts. have ensured the robustness and security of the PUF system, and the practical viability is demonstrated. Such PUF labels could provide a potential platform to realize unbreakable anticounterfeiting.
- 195Chen, M.; Wang, J.; Li, D.; Wang, B.; Wang, S.; Zhao, X.; Meng, M. High-speed and wide-field 3D Raman imaging using flower-like gap-enhanced Raman tags. Appl. Phys. Lett. 2024, 124, 123701, DOI: 10.1063/5.0190009There is no corresponding record for this reference.
- 196Jiang, X.; Tan, Z.; Lin, L.; He, J.; He, C.; Thackray, B. D.; Zhang, Y.; Ye, J. Surface-Enhanced Raman Nanoprobes with Embedded Standards for Quantitative Cholesterol Detection. Small Methods 2018, 2, 1800182, DOI: 10.1002/smtd.201800182There is no corresponding record for this reference.
- 197Zhou, Y.; Zhang, Y.; Xie, H.; Wu, Z.; Shi, B.; Lin, L. L.; Ye, J. In Vivo Surface-Enhanced Transmission Raman Spectroscopy and Impact of Frozen Biological Tissues on Lesion Depth Prediction. ACS Nano 2024, 18 (52), 35393– 35404, DOI: 10.1021/acsnano.4c12469There is no corresponding record for this reference.
- 198Tu, D.; Holderby, A.; Guo, H.; Mabbott, S.; Tian, L.; Coté, G. L. Spectrally multiplexed assay using gap enhanced nanoparticle for detection of a myocardial infarction biomarker panel. Anal. Chim. Acta 2022, 1198, 339562, DOI: 10.1016/j.aca.2022.339562198Spectrally multiplexed assay using gap enhanced nanoparticle for detection of a myocardial infarction biomarker panelTu, Dandan; Holderby, Allison; Guo, Heng; Mabbott, Samuel; Tian, Limei; Cote, Gerard L.Analytica Chimica Acta (2022), 1198 (), 339562CODEN: ACACAM; ISSN:0003-2670. (Elsevier B.V.)Multiplexed assays are essential for the detection of biomarker panels. Differentiating signals from different biomarkers in a single test zone makes the detection more efficient. In this paper, a new method is designed for the synthesis of gap-enhanced nanoparticles (GeNPs) using Raman reporter mols. (RRM) and 6-amino-1-hexanethiol (6-AHT) as the spacer. The GeNPs show a nanometer-size gap, generate strong surface-enhanced Raman scattering (SERS) attributed to the gap, and exhibit discriminative spectral peaks. The strong Au-S bonds on both core and shell sides and the covalent bond between RRM and 6-AHT led to a stable structure, which ensured the stable SERS signal generation from the GeNPs. Using the GeNPs, a spectrally multiplexed assay for the detection of a biomarker panel is developed. The biomarker panel is composed of cardiac troponin I (cTnI), copeptin, and heart-type fatty acid-binding protein (h-FABP), which improves myocardial infarction (MI) diagnostic performance. A paper-based platform that is more amenable to point-of-care diagnostic anal. is used. The developed single biomarker assay achieves limits of detection of 0.01 ng mL-1, 0.86 ng mL-1, 0.004 ng mL-1 for cTnI, h-FABP, and copeptin in buffer solns. The dynamic range of the assay in human serum samples also covers the clin. relevant range of the biomarkers. The cross interference in the multiplexed assay is low. These results show the strong potential of the developed GeNPs in multiplexed detection of biomarkers and the developed simple-to-use multiplexed assay in the diagnosis of MI at the point of care.
- 199Shan, J.; Li, X.; Han, S.; Ren, T.; Jin, M.; Wang, X. Gap-enhance Raman tags (GERTs) competitive immunoassay based Raman imaging for the quantitative detection of trace florfenicol in milk. Food Chem. 2022, 391, 133233, DOI: 10.1016/j.foodchem.2022.133233There is no corresponding record for this reference.
- 200Zhu, S.; Deng, B.; Liu, F.; Li, J.; Lin, L.; Ye, J. Surface-enhanced Raman scattering bioimaging with an ultrahigh signal-to-background ratio under ambient light. ACS Appl. Mater. Interfaces 2022, 14, 8876– 8887, DOI: 10.1021/acsami.2c01063There is no corresponding record for this reference.
- 201Deng, B.; Wang, Y.; Wu, Y.; Yin, W.; Lu, J.; Ye, J. Raman Nanotags-Guided Intraoperative Sentinel Lymph Nodes Precise Location with Minimal Invasion. Advanced Science 2022, 9, 2102405, DOI: 10.1002/advs.202102405There is no corresponding record for this reference.
- 202Zhang, Y.; Lin, L.; He, J.; Ye, J. Optical penetration of surface-enhanced micro-scale spatial offset Raman spectroscopy in turbid gel and biological tissue. Journal of Innovative Optical Health Sciences 2021, 14, 2141001, DOI: 10.1142/S1793545821410017There is no corresponding record for this reference.
- 203Zhang, Y.; Gu, Y.; He, J.; Thackray, B. D.; Ye, J. Ultrabright gap-enhanced Raman tags for high-speed bioimaging. Nat. Commun. 2019, 10, 3905, DOI: 10.1038/s41467-019-11829-y203Ultrabright gap-enhanced Raman tags for high-speed bioimagingZhang Yuqing; Gu Yuqing; He Jing; Thackray Benjamin D; Ye Jian; Zhang Yuqing; Ye Jian; Ye JianNature communications (2019), 10 (1), 3905 ISSN:.Surface-enhanced Raman spectroscopy (SERS) is advantageous over fluorescence for bioimaging due to ultra-narrow linewidth of the fingerprint spectrum and weak photo-bleaching effect. However, the existing SERS imaging speed lags far behind practical needs, mainly limited by Raman signals of SERS nanoprobes. In this work, we report ultrabright gap-enhanced Raman tags (GERTs) with strong electromagnetic hot spots from interior sub-nanometer gaps and external petal-like shell structures, larger immobilization surface area, and Raman cross section of reporter molecules. These GERTs reach a Raman enhancement factor beyond 5 × 10(9) and a detection sensitivity down to a single-nanoparticle level. We use a 370 μW laser to realize high-resolution cell imaging within 6 s and high-contrast (a signal-to-background ratio of 80) wide-area (3.2 × 2.8 cm(2)) sentinel lymph node imaging within 52 s. These nanoprobes offer a potential solution to overcome the current bottleneck in the field of SERS-based bioimaging.
- 204Shi, B.; Li, D.; Yao, W.; Wang, W.; Jiang, J.; Wang, R.; Yan, F.; Liu, H.; Zhang, H.; Ye, J. Multifunctional theranostic nanoparticles for multi-modal imaging-guided CAR-T immunotherapy and chemo-photothermal combinational therapy of non-Hodgkin’s lymphoma. Biomaterials Science 2022, 10, 2577– 2589, DOI: 10.1039/D1BM01982A204Multifunctional theranostic nanoparticles for multi-modal imaging-guided CAR-T immunotherapy and chemo-photothermal combinational therapy of non-Hodgkins lymphomaShi, Bowen; Li, Dan; Yao, Weiwu; Wang, Wenfang; Jiang, Jiang; Wang, Ruiheng; Yan, Fuhua; Liu, Han; Zhang, Huan; Ye, JianBiomaterials Science (2022), 10 (10), 2577-2589CODEN: BSICCH; ISSN:2047-4849. (Royal Society of Chemistry)Accurate and effective tumor diagnosis, detection, and treatment are key for improving the survival rates of patients. Chimeric antigen receptor T (CAR-T) cell therapy has shown remarkable clin. success in eradicating hematol. malignancies. However, the hostile microenvironment in solid tumors severely prevents CAR-T cells from migrating and from infiltrating and killing malignant cells. Tumor microenvironment modulation strategies have attracted much attention in the field of cancer immunotherapy. Multifunctional nanoplatforms that integrate the advantages of different therapeutic techniques can allow for the multimodal synergistic treatment of tumors. In this study, a biocompatible, tumor-targeting, on-demand approach combining CAR-T cell immunotherapy and a chemo-photothermal therapy nanoplatform (FA-Gd-GERTs@Ibrutinib) based on gadolinium-loaded gap-enhanced Raman tags (Gd-GERTs) has been developed for multimodal imaging, and it provides a reliable treatment strategy for solid tumor immunotherapy via microenvironment reconstruction. In our study, folate (FA) receptor targeted mols. are used to improve the accuracy and sensitivity of computed tomog./magnetic resonance/Raman multimodal tumor imaging. The photothermal effect of the nanoprobe can promote the angiogenesis of lymphoma tissue, destroy the extracellular matrix, loosen compact tissue, stimulate chemokine secretion, and effectively enhance the infiltration ability in the case of non-Hodgkins lymphoma, without dampening the CD19 CAR-T cell activity. The treatment results in tumor-bearing mice proved the existence of excellent synergistic therapy; photothermal therapy improves the accumulation and effector function of CAR-T cells within solid tumors. It is believed that multifunctional nanomaterials with targeted multi-modal imaging capabilities that support combination therapy can provide an efficient route for accurate diagnosis and efficient treatment.
- 205Bao, Z.; Deng, B.; Zhang, Y.; Li, X.; Tan, Z.; Gu, Z.; Gu, B.; Shao, Z.; Di, W.; Ye, J. Ratiometric Raman nanotags enable intraoperative detection of metastatic sentinel lymph node. Biomaterials 2021, 276, 121070, DOI: 10.1016/j.biomaterials.2021.121070205Ratiometric Raman nanotags enable intraoperative detection of metastatic sentinel lymph nodeBao, Zhouzhou; Deng, Binge; Zhang, Yuqing; Li, Xiaowei; Tan, Ziyang; Gu, Zhuowei; Gu, Bobo; Shao, Zhifeng; Di, Wen; Ye, JianBiomaterials (2021), 276 (), 121070CODEN: BIMADU; ISSN:0142-9612. (Elsevier Ltd.)Sentinel lymph node (SLN) imaging and biopsy has been advocated as an important technique to evaluate the metastatic status of regional lymph nodes and det. subsequent surgical procedure for many cancers, yet there is no reliable means to provide accurate and rapid diagnosis of metastatic SLN during surgery. Here we develop a new approach, named "Ratiometric Raman dual-nanotag strategy", that using folic acid functionalized targeted and nontargeted gap-enhanced Raman tags (FA-GERTs and Nt-GERTs) to detect metastatic SLN based on Raman imaging combined with classical least square data processing methods. By using this strategy, with built-in self-calibration for signal correction, rather than abs. intensity-dependent signal readout, we realize the visualization and prompt intraoperative diagnosis of metastatic SLN with a high accuracy of 87.5% when the cut-off value of ratio (FA-GERTs/Nt-GERTs) set at 1.255. This approach may outperform the existing histopathol. assessment in diagnosing SLN metastasis and is promising for guiding surgical procedure in the future.
- 206Shi, B.; Zhang, B.; Zhang, Y.; Gu, Y.; Zheng, C.; Yan, J.; Chen, W.; Yan, F.; Ye, J.; Zhang, H. Multifunctional gap-enhanced Raman tags for preoperative and intraoperative cancer imaging. Acta Biomaterialia 2020, 104, 210– 220, DOI: 10.1016/j.actbio.2020.01.006There is no corresponding record for this reference.
- 207Kim, M.; Ko, S. M.; Kim, J.-M.; Son, J.; Lee, C.; Rhim, W.-K.; Nam, J.-M. Dealloyed intra-nanogap particles with highly robust, quantifiable surface-enhanced Raman scattering signals for biosensing and bioimaging applications. ACS Central Science 2018, 4, 277– 287, DOI: 10.1021/acscentsci.7b00584207Dealloyed Intra-Nanogap Particles with Highly Robust, Quantifiable Surface-Enhanced Raman Scattering Signals for Biosensing and Bioimaging ApplicationsKim, Minho; Ko, Sung Min; Kim, Jae-Myoung; Son, Jiwoong; Lee, Chungyeon; Rhim, Won-Kyu; Nam, Jwa-MinACS Central Science (2018), 4 (2), 277-287CODEN: ACSCII; ISSN:2374-7951. (American Chemical Society)Uniformly controlling a large no. of metal nanostructures with a plasmonically enhanced signal to generate quant. optical signals and the widespread use of these structures for surface-enhanced Raman scattering (SERS)-based biosensing and bioimaging applications are of paramount importance but are extremely challenging. Here, the authors report a highly controllable, facile selective-interdiffusive dealloying chem. for synthesizing the dealloyed intra-nanogap particles (DIPs) with a ∼ 2 nm intragap in a high yield (∼95%) without the need for an interlayer. The SERS signals from DIPs are highly quant. and polarization-independent with polarized laser sources. Remarkably, all the analyzed particles displayed the SERS enhancement factors (EFs) of ≥1.1 × 108 with a very narrow distribution of EFs. Finally, DIPs can be used as ultrasensitive SERS-based DNA detection probes for detecting 10 aM to 1 pM target concns. and highly robust, quant. real-time cell imaging probes for long-term imaging with low laser power and short exposure time.
- 208Khlebtsov, N. G.; Lin, L.; Khlebtsov, B. N.; Ye, J. Gap-enhanced Raman tags: fabrication, optical properties, and theranostic applications. Theranostics 2020, 10, 2067– 2094, DOI: 10.7150/thno.39968208Gap-enhanced Raman tags: fabrication, optical properties, and theranostic applicationsKhlebtsov, Nikolai G.; Lin, Li; Khlebtsov, Boris N.; Ye, JianTheranostics (2020), 10 (5), 2067-2094CODEN: THERDS; ISSN:1838-7640. (Ivyspring International Publisher)A review. Gap-enhanced Raman tags (GERTs) are emerging probes of surface-enhanced Raman scattering (SERS) spectroscopy that have found promising anal., bioimaging, and theranostic applications. Because of their internal location, Raman reporter mols. are protected from unwanted external environments and particle aggregation and demonstrate superior SERS responses owing to the strongly enhanced electromagnetic fields in the gaps between metal core-shell structures. In this review, we discuss recent progress in the synthesis, simulation, and exptl. studies of the optical properties and biomedical applications of novel spherically sym. and anisotropic GERTs fabricated with common plasmonic metals-gold (Au) and silver (Ag). Our discussion is focused on the design and synthetic strategies that ensure the optimal parameters and highest enhancement factors of GERTs for sensing and theranostics. In particular, we consider various core-shell structures with build-in nanogaps to explain why they would benefit the plasmonic GERTs as a superior SERS tag and how this would help future research in clin. analytics and therapeutics.
- 209Yang, W.; Lim, D.-K. Recent Advances in the Synthesis of Intra-Nanogap Au Plasmonic Nanostructures for Bioanalytical Applications. Adv. Mater. 2020, 32, 2002219, DOI: 10.1002/adma.202002219209Recent Advances in the Synthesis of Intra-Nanogap Au Plasmonic Nanostructures for Bioanalytical ApplicationsYang, Wonseok; Lim, Dong-KwonAdvanced Materials (Weinheim, Germany) (2020), 32 (51), 2002219CODEN: ADVMEW; ISSN:0935-9648. (Wiley-VCH Verlag GmbH & Co. KGaA)Plasmonic nanogap-enhanced Raman scattering has attracted considerable attention in the fields of Raman-based bioanal. applications and materials science. Various strategies have been proposed to prep. nanostructures with an inter- or intra-nanogap for fundamental study models or applications. This report focuses on recent advances in synthetic methods to fabricate intra-nanogap structures with diverse dimensions, with detailed focus on the theory and bioanal. applications. Synthetic strategies ranging from the use of a silica layer to small mols., the use of polymers and galvanic replacement, are extensively investigated. Furthermore, various core structures, such as spherical, rod-, and cube-shaped, are widely studied, and greatly expand the diversity of plasmonic nanostructures with an intra-nanogap. Theor. calcns., ranging from the first plasmonic hybridization model that is applied to a concentric Au-SiO2-Au nanosphere to the modern quantum cor. model, have evolved to accurately describe the plasmonic resonance property in concentric core-shell nanostructures with a subnanometer nanogap. The greatly enhanced and uniform Raman responses from the localized Raman reporter in the built-in nanogap have made it possible to achieve promising probes with an extraordinary high sensitivity in various formats, such as biomol. detection, high-resoln. cell imaging, and an in vivo imaging application.
- 210Lin, L.; Zapata, M.; Xiong, M.; Liu, Z.; Wang, S.; Xu, H.; Borisov, A. G.; Gu, H.; Nordlander, P.; Aizpurua, J.; Ye, J. Nanooptics of plasmonic nanomatryoshkas: shrinking the size of a core–shell junction to subnanometer. Nano Lett. 2015, 15, 6419– 6428, DOI: 10.1021/acs.nanolett.5b02931210Nanooptics of Plasmonic Nanomatryoshkas: Shrinking the Size of a Core-Shell Junction to SubnanometerLin, Li; Zapata, Mario; Xiong, Min; Liu, Zhonghui; Wang, Shanshan; Xu, Hong; Borisov, Andrei G.; Gu, Hongchen; Nordlander, Peter; Aizpurua, Javier; Ye, JianNano Letters (2015), 15 (10), 6419-6428CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)Quantum effects in plasmonic systems play an important role in defining the optical response of structures with subnanometer gaps. Electron tunneling across the gaps can occur, altering both the far-field optical response and the near-field confinement and enhancement. Plasmon coupling in Au nanomatryoshka (NM) nanoparticles with different core-shell sepns. were exptl. and theor. studied. Plasmon coupling effects between the core and the shell become significant when their sepn. decreases to 15 nm. When their sepn. decreases to <1 nm, the near- and far-field properties can no longer be described by classical approaches but require the inclusion of quantum mech. effects such as electron transport through the self-assembled monolayer of mol. junction. Surface-enhanced Raman scattering measurements indicate strong electron transport-induced charge transfer across the mol. junction. The quantum modeling provides an est. for the a.c. conductances of mols. in the junction. The insights acquired from this work pave the way for the development of novel quantum plasmonic devices and substrates for surface-enhanced Raman scattering.
- 211Lin, L.; Zhang, Q.; Li, X.; Qiu, M.; Jiang, X.; Jin, W.; Gu, H.; Lei, D. Y.; Ye, J. Electron Transport Across Plasmonic Molecular Nanogaps Interrogated with Surface-Enhanced Raman Scattering. ACS Nano 2018, 12, 6492– 6503, DOI: 10.1021/acsnano.7b08224211Electron Transport Across Plasmonic Molecular Nanogaps Interrogated with Surface-Enhanced Raman ScatteringLin, Li; Zhang, Qiang; Li, Xiyao; Qiu, Meng; Jiang, Xin; Jin, Wei; Gu, Hongchen; Lei, Dang Yuan; Ye, JianACS Nano (2018), 12 (7), 6492-6503CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Charge transport plays an important role in defining both far-field and near-field optical response of a plasmonic nanostructure with an ultrasmall built-in nanogap. As the gap size of a Au core-shell nanomatryoshka approaches the sub-nanometer length scale, charge transport may occur and strongly alter the near-field enhancement within the mol.-filled nanogap. Ultrasensitive surface-enhanced Raman spectroscopy (SERS) was used to study the plasmonic near-field variation induced by the mol. junction conductance-assisted electron transport in Au nanomatryoshkas, termed gap-enhanced Raman tags (GERTs). The GERTs, with interior gaps from 0.7 to 2 nm, are prepd. with a wet chem. method. The exptl. and theor. studies suggest that the electron transport through the mol. junction influences both far-field and near-field optical properties of the GERTs. In the far-field extinction response, the low-energy gap mode predicted by a classical electromagnetic model (CEM) is strongly quenched and hence unobservable in the expt., which can be well explained by a quantum-cor. model (QCM). In the near-field SERS response, the optimal gap size for max. Raman enhancement at the excitation wavelength of 785 nm (633 nm) is ∼1.35 nm (1.8 nm). Similarly, these near-field results do not tally with the CEM calcns. but agree well with the QCM results where the mol. junction conductance in the nanogap is fully considered. The study may improve understanding of charge-transport phenomena in ultrasmall plasmonic mol. nanogaps and promote the further development of mol. electronics-based plasmonic nanodevices.
- 212Lin, L.; Ji, W.; Zhang, L.-W.; Ye, J. Atomic Insights into the Evolution of Three-Dimensional Molecular Junctions in Plasmonic Core–Shell Nanoparticles. J. Phys. Chem. C 2021, 125, 1865– 1873, DOI: 10.1021/acs.jpcc.0c09552There is no corresponding record for this reference.
- 213Li, J.; Liu, F.; He, C.; Shen, F.; Ye, J. Orthogonal gap-enhanced Raman tags for interference-free and ultrastable surface-enhanced Raman scattering. Nanophotonics 2022, 11, 1549– 1560, DOI: 10.1515/nanoph-2021-0689213Orthogonal gap-enhanced Raman tags for interference-free and ultrastable surface-enhanced Raman scatteringLi, Jin; Liu, Fugang; He, Chang; Shen, Feng; Ye, JianNanophotonics (2022), 11 (8), 1549-1560CODEN: NANOLP; ISSN:2192-8614. (Walter de Gruyter GmbH)Spectral interference from backgrounds is not negligible for surface-enhanced Raman scattering (SERS) tags and often influences the accuracy and reliability of SERS applications. We report the design and synthesis of orthogonal gap-enhanced Raman tags (O-GERTs) by embedding alkyne and deuterium-based reporters in the interior metallic nanogaps of core-shell nanoparticles and explore their signal orthogonality as optical probes against different backgrounds from common substrates and media (e.g., glass and polymer) to related targets (e.g., bacteria, cancer cells, and tissues). Proof-of-concept expts. show that the O-GERT signals in the fingerprint region (200-1800 cm-1) are likely interfered by various backgrounds, leading to difficulty of accurate quantification, while the silent-region (1800-2800 cm-1) signals are completely interference-free. Moreover, O-GERTs show much higher photo and biol. stability compared to conventional SERS tags. This work not only demonstrates O-GERTs as universal optical tags for accurate and reliable detection onto various substrates and in complex media, but also opens new opportunities in a variety of frontier applications, such as three-dimensional data storage and security labeling.
- 214Fan, S.; Scarpitti, B. T.; Luo, Z.; Smith, A. E.; Ye, J.; Schultz, Z. D. Facile synthesis of intra-nanogap enhanced Raman tags with different shapes. Nano Research 2024, 17, 8415– 8423, DOI: 10.1007/s12274-024-6807-yThere is no corresponding record for this reference.
- 215Shen, J.; Jiang, X.; Xu, L.; Ge, Z.; Li, Q.; Song, B.; Wang, L.; Song, S. Poly-Adenine-Engineered Gold Nanogaps for SERS Nanostructures. ACS Applied Nano Materials 2019, 2, 3501– 3509, DOI: 10.1021/acsanm.9b00473215Poly-Adenine-Engineered Gold Nanogaps for SERS NanostructuresShen, Jianlei; Jiang, Xiankai; Xu, Lifeng; Ge, Zhilei; Li, Qian; Song, Bo; Wang, Lihua; Song, ShipingACS Applied Nano Materials (2019), 2 (6), 3501-3509CODEN: AANMF6; ISSN:2574-0970. (American Chemical Society)Surface-enhanced Raman scattering (SERS) effect, usually is assocd. with the highly confined electromagnetic field in plasmonic nanostructures, and has been widely investigated for mol. sensing and imaging applications. However, SERS substrates have confronted with poor reproducibility and inefficient nanometer-level structural control. By employing oligonucleotides, highly reproducible SERS substrates with uniform 1 nm nanogap could be constructed. In this work, we investigated the effect of oligonucleotides, esp. the unmodified oligonucleotides, on the morphol. of nanogaps. We found that the morphol. of nanogap is dependent on the sequence, length, and surface-coating d. of the unmodified oligonucleotide and speculate that the formation of nanogaps is dominated by stable self-assembled monolayers (SAMs) of unmodified oligonucleotides, which is supported by mol. dynamic simulation (MD) results. We further studied the morphologies of nanogaps, with oligonucleotide SAMs of different states and nanoseeds of different sizes and shapes. This work elucidated the relationships between the SAMs of unmodified oligonucleotides and the morphol. of nanogaps, which will facilitate the design of reliable SERS nanostructures.
- 216Kim, J.-M.; Kim, J.; Choi, K.; Nam, J.-M. Plasmonic Dual-Gap Nanodumbbells for Label-Free On-Particle Raman DNA Assays. Adv. Mater. 2023, 35, 2208250, DOI: 10.1002/adma.202208250There is no corresponding record for this reference.
- 217Acapulco, J. A. I.; Hong, S.; Kim, S. K.; Park, S. Controlling optical properties of metallic multi-shell nanoparticles through suppressed surface plasmon resonance. J. Colloid Interface Sci. 2016, 461, 376– 382, DOI: 10.1016/j.jcis.2015.09.040There is no corresponding record for this reference.
- 218Lin, L.; He, H.; Xue, R.; Zhang, Y.; Wang, Z.; Nie, S.; Ye, J. Direct and quantitative assessments of near-infrared light attenuation and spectroscopic detection depth in biological tissues using surface-enhanced Raman scattering. Med-X 2023, 1, 9, DOI: 10.1007/s44258-023-00010-2There is no corresponding record for this reference.
- 219Khlebtsov, B. N.; Burov, A. M.; Bratashov, D. N.; Tumskiy, R. S.; Khlebtsov, N. G. Petal-like Gap-Enhanced Raman Tags with Controllable Structures for High-Speed Raman Imaging. Langmuir 2020, 36, 5546– 5553, DOI: 10.1021/acs.langmuir.0c00623219Petal-like Gap-Enhanced Raman Tags with Controllable Structures for High-Speed Raman ImagingKhlebtsov, Boris N.; Burov, Andrey M.; Bratashov, Daniil N.; Tumskiy, Roman S.; Khlebtsov, Nikolai G.Langmuir (2020), 36 (20), 5546-5553CODEN: LANGD5; ISSN:0743-7463. (American Chemical Society)Surface-enhanced Raman scattering (SERS) is widely used for in vitro and in vivo bioimaging applications. However, reproducible and controllable fabrication of SERS tags with high d. of electromagnetic hot-spots is still challenging. We report an improved strategy for the synthesis of core/shell Raman tags with high d. of hot-spots and high immobilization of reporter mols. The strategy is based on simultaneous growth and functionalization of an Au shell around Au nanospheres coated with 4-nitrobenzenethiol (NBT). The amt. of added 4-NBT is key factor to control the structure SERS response of the resulting particles. Specifically, we demonstrate the formation of gap-enhanced Raman tags (GERTs) with a smooth solid shell (sGERTs), petal-like GERTs (pGERTs), and mesoporous Au particles (mGERTs) filled with Raman mols. In contrast to NBT mols., similar thiols such as 1,4-benzenedithiol (BDT) and 2-naphtalenethiol (NT) do not support the formation of pGERTs and mGERTs. To explain this finding, we proposed a growth mechanism based on the unique chem. structure of NBT. The SERS response of optimized pGERTs is 50 times higher than that from usual sGERTs, which makes pGERTs suitable for single-particle spectroscopy. We demonstrate successful application of pGERTs for high-speed cell imaging using 10 ms accumulation time per pixel and a total imaging time of about 1 min. Because of the high SERS response and unique porous structure, these nanoparticles have great potential for bioimaging and other applications.
- 220Chen, M.; Zhao, X.; Wang, B.; Liu, H.; Chen, Z.; Sun, L.; Xu, X. Graphene-wrapped petal-like gap-enhanced Raman tags for enhancing photothermal conversion and Raman imaging. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 2024, 304, 123306, DOI: 10.1016/j.saa.2023.123306There is no corresponding record for this reference.
- 221Zhang, M.; Xu, S.; Guan, P.-C.; Zhang, Y.-J.; Li, J.-F. Application of Gap Mode Ultrasensitive P-GERTs in SERS-Based Rapid Detection. Photonics 2024, 11, 708, DOI: 10.3390/photonics11080708There is no corresponding record for this reference.
- 222Lee, J. H.; Oh, J. W.; Nam, S. H.; Cha, Y. S.; Kim, G. H.; Rhim, W. K.; Kim, N. H.; Kim, J.; Han, S. W.; Suh, Y. D.; Nam, J. M. Synthesis, Optical Properties, and Multiplexed Raman Bio-Imaging of Surface Roughness-Controlled Nanobridged Nanogap Particles. Small 2016, 12, 4726– 34, DOI: 10.1002/smll.201600289222Synthesis, Optical Properties, and Multiplexed Raman Bio-Imaging of Surface Roughness-Controlled Nanobridged Nanogap ParticlesLee, Jung-Hoon; Oh, Jeong-Wook; Nam, Sang Hwan; Cha, Yeong Seok; Kim, Gyeong-Hwan; Rhim, Won-Kyu; Kim, Nam Hoon; Kim, Jongwoo; Han, Sang Woo; Suh, Yung Doug; Nam, Jwa-MinSmall (2016), 12 (34), 4726-4734CODEN: SMALBC; ISSN:1613-6810. (Wiley-VCH Verlag GmbH & Co. KGaA)Plasmonic nanostructures are widely studied and used because of their useful size, shape, compn. and assembled structure-based plasmonic properties. It is, however, highly challenging to precisely design, reproducibly synthesize and reliably utilize plasmonic nanostructures with enhanced optical properties. Here, we devise a facile synthetic method to generate Au surface roughness-controlled nanobridged nanogap particles (Au-RNNPs) with ultrasmall (≈1 nm) interior gap and tunable surface roughness in a highly controllable manner. Importantly, we found that particle surface roughness can be assocd. with and enhance the electromagnetic field inside the interior gap, and stronger nanogap-enhanced Raman scattering (NERS) signals can be generated from particles by increasing particle surface roughness. The finite-element method-based calcn. results support and are matched well with the exptl. results and suggest one needs to consider particle shape, nanogap and nanobridges simultaneously to understand and control the optical properties of this type of nanostructures. Finally, the potential of multiplexed Raman detection and imaging with RNNPs and the high-speed, high-resoln. Raman bio-imaging of Au-RNNPs inside cells with a wide-field Raman imaging setup with liq. crystal tunable filter are demonstrated. Our results provide strategies and principles in designing and synthesizing plasmonically enhanced nanostructures and show potential for detecting and imaging Raman nanoprobes in a highly specific, sensitive and multiplexed manner.
- 223Chen, S.; Fan, J.; Lv, M.; Hua, C.; Liang, G.; Zhang, S. Internal Standard Assisted Surface-Enhanced Raman Scattering Nanoprobe with 4-NTP as Recognition Unit for Ratiometric Imaging Hydrogen Sulfide in Living Cells. Anal. Chem. 2022, 94, 14675– 14681, DOI: 10.1021/acs.analchem.2c02961There is no corresponding record for this reference.
- 224Zhang, W.; Rahmani, M.; Niu, W.; Ravaine, S.; Hong, M.; Lu, X. Tuning Interior Nanogaps of Double-shelled Au/Ag Nanoboxes for Surface-Enhanced Raman Scattering. Sci. Rep. 2015, 5, 8382, DOI: 10.1038/srep08382224Tuning Interior Nanogaps of Double-shelled Au/Ag Nanoboxes for Surface-Enhanced Raman ScatteringZhang, Weiqing; Rahmani, Mohsen; Niu, Wenxin; Ravaine, Serge; Hong, Minghui; Lu, XianmaoScientific Reports (2015), 5 (), 8382CODEN: SRCEC3; ISSN:2045-2322. (Nature Publishing Group)Double-shelled Au/Ag hollow nanoboxes with precisely controlled interior nanogaps (1 to 16 nm) were synthesized for gap-tunable surface-enhanced Raman scattering (SERS). The double-shelled nanoboxes were prepd. via a two-step galvanic replacement reaction approach using Ag nanocubes as the templates, while 4-aminothiolphenol (4-ATP) as SERS probe mols. were loaded between the two shells. More than 10-fold enhancement of SERS is obsd. from the double-shelled nanoboxes than Ag nanocubes. In addn., the SERS of the double-shelled nanoboxes increase significantly with the decrease of gap size, consistent with the theor. prediction that smaller gap size induces larger localized electromagnetic enhancement.
- 225Jin, X.; Khlebtsov, B. N.; Khanadeev, V. A.; Khlebtsov, N. G.; Ye, J. Rational Design of Ultrabright SERS Probes with Embedded Reporters for Bioimaging and Photothermal Therapy. ACS Appl. Mater. Interfaces 2017, 9, 30387– 30397, DOI: 10.1021/acsami.7b08733225Rational Design of Ultrabright SERS Probes with Embedded Reporters for Bioimaging and Photothermal TherapyJin, Xiulong; Khlebtsov, Boris N.; Khanadeev, Vitaly A.; Khlebtsov, Nikolai G.; Ye, JianACS Applied Materials & Interfaces (2017), 9 (36), 30387-30397CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Plasmonic nanoparticles can be utilized as surface-enhanced Raman scattering (SERS) probes for bioimaging and as photothermal (PT) agents for cancer therapy. Typically, their SERS and PT efficiencies reach maximal values under the on-resonant condition, when the excitation wavelength overlaps the localized surface plasmon resonance (LSPR) wavelength preferably in the near-IR (NIR) biol. window. However, the photogenerated heat may inevitably disturb or even destroy biol. samples during the imaging process. Herein, the authors develop ultrabright SERS probes composed of metallic Au@Ag core-shell rodlike nanomatryoshkas (RNMs) with embedded Raman reporters. By rationally controlling the Ag shell thickness, the LSPR of RNMs can be tuned from UV to NIR range, resulting in highly tunable SERS and PT properties. As bright NIR SERS imaging nanoprobes, RNMs with a thick Ag shell are designed for minimal PT damage to the biol. targets under the off-resonance condition, as illustrated through monitoring the changes in mitochondrial membrane potential of cancer cells during SERS imaging procedure. By contrast, RNMs with a thin Ag shell are designed as multifunctional NIR theranostic probes that combine enhanced photothermal therapy capability, as exemplified by efficient PT killing of cancer cells, with reduced yet still efficient imaging properties at the on-resonance excitation.
- 226Zhang, Y.; Chen, R.; Liu, F.; Miao, P.; Lin, L.; Ye, J. In Vivo Surface-Enhanced Transmission Raman Spectroscopy under Maximum Permissible Exposure: Toward Photosafe Detection of Deep-Seated Tumors. Small Methods 2023, 7, 2201334, DOI: 10.1002/smtd.202201334There is no corresponding record for this reference.
- 227Prodan, E.; Radloff, C.; Halas, N. J.; Nordlander, P. A hybridization model for the plasmon response of complex nanostructures. Science 2003, 302, 419– 22, DOI: 10.1126/science.1089171227A hybridization model for the plasmon response of complex nanostructuresProdan, E.; Radloff, C.; Halas, N. J.; Nordlander, P.Science (Washington, DC, United States) (2003), 302 (5644), 419-422CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)The authors present a simple and intuitive picture, an electromagnetic analog of MO theory, that describes the plasmon response of complex nanostructures of arbitrary shape. The authors' model can be understood as the interaction or hybridization of elementary plasmons supported by nanostructures of elementary geometries. As an example, the approach is applied to the important case of a four-layer concentric nanoshell, where the hybridization of the plasmons of the inner and outer nanoshells dets. the resonant frequencies of the multilayer nanostructure.
- 228Savage, K. J.; Hawkeye, M. M.; Esteban, R.; Borisov, A. G.; Aizpurua, J.; Baumberg, J. J. Revealing the quantum regime in tunnelling plasmonics. Nature 2012, 491, 574– 7, DOI: 10.1038/nature11653228Revealing the quantum regime in tunnelling plasmonicsSavage, Kevin J.; Hawkeye, Matthew M.; Esteban, Ruben; Borisov, Andrei G.; Aizpurua, Javier; Baumberg, Jeremy J.Nature (London, United Kingdom) (2012), 491 (7425), 574-577CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)When 2 metal nanostructures are placed nanometers apart, their optically driven free electrons couple elec. across the gap. The resulting plasmons have enhanced optical fields of a specific color tightly confined inside the gap. Many emerging nanophotonic technologies depend on the careful control of this plasmonic coupling, including optical nanoantennas for high-sensitivity chem. and biol. sensors, nanoscale control of active devices, and improved photovoltaic devices. But for subnanometre gaps, coherent quantum tunnelling becomes possible and the system enters a regime of extreme nonlocality in which previous classical treatments fail. Electron correlations across the gap that are driven by quantum tunnelling require a new description of nonlocal transport, which is crucial in nanoscale optoelectronics and single-mol. electronics. Here, by simultaneously measuring both the elec. and optical properties of 2 Au nanostructures with controllable subnanometre sepn., the authors reveal the quantum regime of tunnelling plasmonics in unprecedented detail. All obsd. phenomena are in good agreement with recent quantum-based models of plasmonic systems, which eliminate the singularities predicted by classical theories. These findings imply that tunnelling establishes a quantum limit for plasmonic field confinement of ∼10-8λ3 for visible light (of wavelength λ). Work thus prompts new theor. and exptl. studies into quantum-domain plasmonic systems, and will affect the future of nanoplasmonic device engineering and nanoscale photochem.
- 229Song, Z.-L.; Chen, Z.; Bian, X.; Zhou, L.-Y.; Ding, D.; Liang, H.; Zou, Y.-X.; Wang, S.-S.; Chen, L.; Yang, C.; Zhang, X.-B.; Tan, W. Alkyne-Functionalized Superstable Graphitic Silver Nanoparticles for Raman Imaging. J. Am. Chem. Soc. 2014, 136, 13558– 13561, DOI: 10.1021/ja507368z229Alkyne-Functionalized Superstable Graphitic Silver Nanoparticles for Raman ImagingSong, Zhi-Ling; Chen, Zhuo; Bian, Xia; Zhou, Li-Yi; Ding, Ding; Liang, Hao; Zou, Yu-Xiu; Wang, Shan-Shan; Chen, Long; Yang, Chao; Zhang, Xiao-Bing; Tan, WeihongJournal of the American Chemical Society (2014), 136 (39), 13558-13561CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Noble metals, esp. gold, have been widely used in plasmon resonance applications. Although silver has a larger optical cross section and lower cost than gold, it has attracted much less attention because of its easy corrosion, thereby degrading plasmonic signals and limiting its applications. To circumvent this problem, the authors report the facile synthesis of superstable AgCu@graphene (ACG) nanoparticles (NPs). The growth of several layers of graphene onto the surface of AgCu alloy NPs effectively protects the Ag surface from contamination, even in the presence of hydrogen peroxide, hydrogen sulfide, and nitric acid. The ACG NPs have been used to enhance the unique Raman signals from the graphitic shell, making ACG an ideal candidate for cell labeling, rapid Raman imaging, and SERS detection. ACG is further functionalized with alkyne-polyethylene glycol, which has strong Raman vibrations in the Raman-silent region of the cell, leading to more accurate colocalization inside cells. In sum, this work provides a simple approach to fabricate corrosion-resistant, water-sol., and graphene-protected AgCu NPs having a strong surface plasmon resonance effect suitable for sensing and imaging.
- 230Palla, M.; Kumar, S.; Li, Z.; Jockusch, S.; Russo, J. J.; Ju, J.; Bosco, F. G.; Rindzevicius, T.; Alstrom, T. S.; Schmidt, M. S.; Boisen, A. Click chemistry based biomolecular conjugation monitoring using surface-enhanced Raman spectroscopy mapping; IEEE SENSORS , 30 Oct.–3 Nov. 2016; pp 1– 3. DOI: 10.1109/ICSENS.2016.7808595 .There is no corresponding record for this reference.
- 231Kong, K. V.; Lam, Z.; Goh, W. D.; Leong, W. K.; Olivo, M. Metal Carbonyl-Gold Nanoparticle Conjugates for Live-Cell SERS Imaging. Angew. Chem. Int. Edit 2012, 51, 9796– 9799, DOI: 10.1002/anie.201204349231Metal Carbonyl-Gold Nanoparticle Conjugates for Live-Cell SERS ImagingKong, Kien Voon; Lam, Zhiyong; Goh, Wenda Douglas; Leong, Weng Kee; Olivo, MaliniAngewandte Chemie, International Edition (2012), 51 (39), 9796-9799, S9796/1-S9796/7CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)A novel metal carbonyl-based biotag has been prepd. by combining osmium carbonyl clusters and gold nanoparticles, as an example of an organometallic-nanoparticle (OM-NP) conjugate. These OM-NP conjugates display excellent aq. dispersibility and storage stability. Furthermore, they can be readily functionalized with suitable binding ligands to produce biol. functional OM-NP-L conjugates, which the authors have demonstrated in live-cell imaging. It shows clearly the advantage of transition-metal carbonyl compds., for which the CO stretching vibration signal is well-sepd. from other mol. vibrational modes of the cell, in live-cell imaging. In addn., in comparison to the other detection modes, the authors' approach offers both greater sensitivity (signal strength and signal-to-noise) and good spatial resoln.
- 232Stiles, P. L.; Dieringer, J. A.; Shah, N. C.; Van Duyne, R. P. Surface-enhanced Raman spectroscopy. Annu. Rev. Anal Chem. (Palo Alto Calif) 2008, 1, 601– 26, DOI: 10.1146/annurev.anchem.1.031207.112814232Surface-enhanced Raman spectroscopyStiles Paul L; Dieringer Jon A; Shah Nilam C; Van Duyne Richard PAnnual review of analytical chemistry (Palo Alto, Calif.) (2008), 1 (), 601-26 ISSN:.The ability to control the size, shape, and material of a surface has reinvigorated the field of surface-enhanced Raman spectroscopy (SERS). Because excitation of the localized surface plasmon resonance of a nanostructured surface or nanoparticle lies at the heart of SERS, the ability to reliably control the surface characteristics has taken SERS from an interesting surface phenomenon to a rapidly developing analytical tool. This article first explains many fundamental features of SERS and then describes the use of nanosphere lithography for the fabrication of highly reproducible and robust SERS substrates. In particular, we review metal film over nanosphere surfaces as excellent candidates for several experiments that were once impossible with more primitive SERS substrates (e.g., metal island films). The article also describes progress in applying SERS to the detection of chemical warfare agents and several biological molecules.
- 233Shao, F.; Lu, Z.; Liu, C.; Han, H.; Chen, K.; Li, W.; He, Q.; Peng, H.; Chen, J. Hierarchical Nanogaps within Bioscaffold Arrays as a High-Performance SERS Substrate for Animal Virus Biosensing. Acs Appl. Mater. Inter 2014, 6, 6281– 6289, DOI: 10.1021/am4045212233Hierarchical Nanogaps within Bioscaffold Arrays as a High-Performance SERS Substrate for Animal Virus BiosensingShao, Feng; Lu, Zhicheng; Liu, Chen; Han, Heyou; Chen, Kun; Li, Wentao; He, Qigai; Peng, Hui; Chen, JuanniACS Applied Materials & Interfaces (2014), 6 (9), 6281-6289CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)A three-dimensional (3D) biomimetic SERS substrate with hierarchical nanogaps was formed on the bioscaffold arrays of cicada wings by one-step and reagents-free ion-sputtering techniques. This approach requires a minimal fabrication effort and cost and offers Ag nanoislands and Ag nanoflowers with four types of nanogaps (<10 nm) on the chitin nanopillars to generate a high d. of hotspots (∼2000/μm2). The 3D biomimetic substrate shows a low detection limit to Rhodamine 6G (10-13 M), high av. enhancement factor (EF, 5.8 × 107), excellent signal uniformity (5.4%), good stability, and suitability in biosensing. Furthermore, the finite-difference time-domain (FDTD) elec.-field-distribution simulations illustrate that the 3D biomimetic SERS substrate provides the high-d. hotspot area within a detection vol., resulting in enormous SERS enhancement. In addn., the conspicuous far-field plasmon resonance peaks were not found to be a strong requirement for a high EF in 3D biomimetic substrates. Addnl., the novel substrate was applied in label-free animal viruses detection and differentiation with small amts. (1.0 μL) and low concns. of analyte (1 × 103 PFU/mL), and it exhibited potential as an effective SERS platform for virus detection and sensing.
- 234Liu, H.-L.; Cao, J.; Hanif, S.; Yuan, C.; Pang, J.; Levicky, R.; Xia, X.-H.; Wang, K. Size-Controllable Gold Nanopores with High SERS Activity. Anal. Chem. 2017, 89, 10407– 10413, DOI: 10.1021/acs.analchem.7b02410234Size-Controllable Gold Nanopores with High SERS ActivityLiu, Hai-Ling; Cao, Jiao; Hanif, Sumaira; Yuan, Chunge; Pang, Jie; Levicky, Rastislav; Xia, Xing-Hua; Wang, KangAnalytical Chemistry (Washington, DC, United States) (2017), 89 (19), 10407-10413CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Nanopore structures have been successfully employed in next-generation DNA sequencing. For more complicated protein which normally contains 20 different amino acids, identifying the fluctuation of ionic current caused by different amino acids appears inadequate for protein sequencing. Therefore, it is highly desirable to develop size-controllable nanopores with optical activity that can provide addnl. structural information. Herein, the authors discovered the novel nanopore properties of the self-assembled ultramicroelectrodes originally developed by Bard and coworkers. Using a slightly modified method, the self-assembly of 7±1 nm gold nanoparticles (AuNPs) can be precisely controlled to form a gold nanoporous sphere (GPS) on the tip of a glass capillary. Different dithiol linker mols. (1,3-propanedithiol, C3; 1,6-hexanedithiol, C6; and 1,9-nonanedithiol, C9) reproducibly led to rather similar nanopore sizes (5.07±0.02, 5.13±0.02, and 5.25±0.01 nm), resp. The GPS nanostructures were found to exhibit high ionic current rectification as well as surface-enhanced Raman scattering (SERS) activity due to the presence of nanopores and numerous "hot spots" among the crosslinked AuNPs on the surface of GPS. The rectification effect of the small nanopores was obsd. even under high concn. of electrolyte (290 mM), along with SERS enhancement factors well above 1 × 105. The GPS nanostructures were successfully applied for SERS-based detection of glutathione from a single HeLa cell.
- 235Martin, L. C.; Larmour, I. A.; Faulds, K.; Graham, D. Turning up the lights─fabrication of brighter SERRS nanotags. Chem. Commun. 2010, 46, 5247– 5249, DOI: 10.1039/c0cc00722fThere is no corresponding record for this reference.
- 236Huang, Y.; Swarup, V. P.; Bishnoi, S. W. Rapid Raman Imaging of Stable, Functionalized Nanoshells in Mammalian Cell Cultures. Nano Lett. 2009, 9, 2914– 2920, DOI: 10.1021/nl901234x236Rapid Raman Imaging of Stable, Functionalized Nanoshells in Mammalian Cell CulturesHuang, Yiming; Swarup, Vimal P.; Bishnoi, Sandra WhaleyNano Letters (2009), 9 (8), 2914-2920CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)Two Raman-active poly(ethylene glycol) (PEG) mols., one linear (MW 5000) and the other branched (MW 2420), are synthesized to stabilize gold-silica nanoshells in cell culture media and track nanoparticles in mammalian cell cultures. The linear PEG provides greater nanoshell stability in saline soln. compared to com. available PEG-thiol or the branched PEG. Surface enhanced Raman scattering rapidly tracks the probes and provides semiquant. information regarding particle localization within mouse macrophage (RAW 264.7) and human breast cancer (MCF 7) cell cultures.
- 237Kneipp, K.; Kneipp, H.; Itzkan, I.; Dasari, R. R.; Feld, M. S. Ultrasensitive Chemical Analysis by Raman Spectroscopy. Chem. Rev. 1999, 99, 2957– 2976, DOI: 10.1021/cr980133r237Ultrasensitive chemical analysis by Raman spectroscopyKneipp, Katrin; Kneipp, Harald; Itzkan, Irving; Dasari, Ramachandra R.; Feld, Michael S.Chemical Reviews (Washington, D. C.) (1999), 99 (10), 2957-2975CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review with 133 refs. is given on surface-enhanced Raman scattering, single-mol. Raman spectroscopy, crit. anal. and prospects of single-mol. Raman spectroscopy.
- 238McNay, G.; Eustace, D.; Smith, W. E.; Faulds, K.; Graham, D. Surface-Enhanced Raman Scattering (SERS) and Surface-Enhanced Resonance Raman Scattering (SERRS): A Review of Applications. Appl. Spectrosc. 2011, 65, 825– 837, DOI: 10.1366/11-06365238Surface-enhanced Raman scattering (SERS) and surface-enhanced resonance Raman scattering (SERRS): a review of applicationsMcNay, Graeme; Eustace, David; Smith, W. Ewen; Faulds, Karen; Graham, DuncanApplied Spectroscopy (2011), 65 (8), 825-837CODEN: APSPA4; ISSN:0003-7028. (Society for Applied Spectroscopy)A review. Surface-enhanced Raman scattering (SERS) and surface-enhanced resonance Raman scattering (SERRS) can provide pos. identification of an analyte or an analyte mixt. with high sensitivity and selectivity. Better understanding of the theory and advances in the understanding of the practice have led to the development of practical applications in which the unique advantages of SERS/SERRS have been used to provide effective solns. to difficult anal. problems. This review presents a basic theory and illustrates the way in which SERS/SERRS has been developed for practical use.
- 239Chen, Y.; Ren, J.-Q.; Zhang, X.-G.; Wu, D.-Y.; Shen, A.-G.; Hu, J.-M. Alkyne-modulated surface-enhanced Raman scattering-palette for optical interference-free and multiplex cellular imaging. Anal. Chem. 2016, 88, 6115– 6119, DOI: 10.1021/acs.analchem.6b01374239Alkyne-Modulated Surface-Enhanced Raman Scattering-Palette for Optical Interference-Free and Multiplex Cellular ImagingChen, Yong; Ren, Jia-Qiang; Zhang, Xia-Guang; Wu, De-Yin; Shen, Ai-Guo; Hu, Ji-MingAnalytical Chemistry (Washington, DC, United States) (2016), 88 (12), 6115-6119CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)The alkyne tags possess unique interference-free Raman emissions but are still hindered for further application in the field of biochem. labels due to its extremely weak spontaneous Raman scattering. With the aid of computational chem., herein, an alkyne-modulated surface-enhanced Raman scattering (SERS) palette is constructed based on rationally designed 4-ethynylbenzenethiol derivs. for spectroscopic signature, Au@Ag core for optical enhancement and an encapsulating polyallylamine shell for protection and conjugation. Even for the pigment rich plant cell (e.g., pollen), the alkyne-coded SERS tag can be highly discerned on two-dimension distribution impervious to strong org. interferences originating from resonance-enhanced Raman scattering or autofluorescence. In addn., the alkynyl-contg. Raman reporters contribute esp. narrow emission, band shift-tunable (2100-2300 cm-1) and tremendously enhanced Raman signals when the alkynyl group locates at para position of mercaptobenzene ring. Depending on only single Raman band, the suggested alkyne-modulated SERS-palette potentially provides a more effective soln. for multiplex cellular imaging with vibrant colors, when the hyperspectral and fairly intense optical noises originating from lower wavenumber region (<1800 cm-1) are inevitable under complex ambient conditions.
- 240Zeng, Y.; Ren, J.-Q.; Shen, A.-G.; Hu, J.-M. Splicing Nanoparticles-Based “Click” SERS Could Aid Multiplex Liquid Biopsy and Accurate Cellular Imaging. J. Am. Chem. Soc. 2018, 140, 10649– 10652, DOI: 10.1021/jacs.8b04892240Splicing Nanoparticles-Based "Click" SERS Could Aid Multiplex Liquid Biopsy and Accurate Cellular ImagingZeng, Yi; Ren, Jia-Qiang; Shen, Ai-Guo; Hu, Ji-MingJournal of the American Chemical Society (2018), 140 (34), 10649-10652CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Here, a completely new readout technique, so-called "Click" SERS, has been developed based on Raman scattered light splice derived from nanoparticle (NP) assemblies. The single and narrow (1-2 nm) emission originating from triple bond-contg. reporters undergoes dynamic combinatorial output, by controllable splice of SERS-active NPs analogous to small mol. units in click chem. Entirely different to conventional "sole code related to sole target" readout protocol, the intuitional, predictable and uniquely identifiable "Click" SERS is relies on the no. rather than the intensity of combinatorial emissions. By this technique, 10-plex synchronous biomarkers detection under a single scan, and accurate cellular imaging under double exposure have been achieved. "Click" SERS demonstrated multiple single band Raman scattering could be an authentic optical anal. method in biomedicine.
- 241Bai, X.-R.; Wang, L.-H.; Ren, J.-Q.; Bai, X.-W.; Zeng, L.-W.; Shen, A.-G.; Hu, J.-M. Accurate Clinical Diagnosis of Liver Cancer Based on Simultaneous Detection of Ternary Specific Antigens by Magnetic Induced Mixing Surface-Enhanced Raman Scattering Emissions. Anal. Chem. 2019, 91, 2955– 2963, DOI: 10.1021/acs.analchem.8b05153241Accurate Clinical Diagnosis of Liver Cancer Based on Simultaneous Detection of Ternary Specific Antigens by Magnetic Induced Mixing Surface-Enhanced Raman Scattering EmissionsBai, Xiang-Ru; Wang, Li-Hua; Ren, Jia-Qiang; Bai, Xiang-Wei; Zeng, Ling-Wen; Shen, Ai-Guo; Hu, Ji-MingAnalytical Chemistry (Washington, DC, United States) (2019), 91 (4), 2955-2963CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Establishing an accurate, simple, and rapid serodiagnosis method aiming for specific cancer antigens is critically important for the clin. diagnosis, therapy, and prognostication of cancer. Currently, surface-enhanced Raman scattering (SERS) readout techniques challenge fluorescent-based detection methods in terms of both optical stability and more importantly multiple detection capability, which become more desirable for clin. diagnostics. The authors thus started using an interference-free mixing SERS emission (m-SERS) readout to simultaneously indicate, for the first time, three specific liver cancer antigens, including α-fetoprotein (AFP), carcinoembryonic antigen (CEA), and ferritin (FER), even in one clin. serum sample. Here, three triple bonds (C≡N and C≡C) coded SERS tags contribute sep. SERS emissions located at 2105, 2159, and 2227 cm-1, resp.; must have one-to-one correspondence from AFP, to FER, to CEA, In the process of detection, the mature double antibody sandwich gave microscale core-satellite assembly structure between a magnetic bead (MB) and single SERS tags, and therefore a pure and single SERS emission can be obsd. under the routine excitation laser spot. Because of the action of magnetic force, the uniform 3D packing of SERS tags absorbed MBs will in contrast generate a so-called m-SERS signals. With the help of enrichment and sepn. by MBs, the proposed m-SERS immunoassay provides an extremely rapid, sensitive, and accurate soln. for multiplex detection of antigens or other biomarkers. Herein, the limit of detection (LOD) for simultaneous m-SERS detection of AFP, CEA, and FER was 0.15, 20, and 4 pg/mL, resp. As expected for 39 clin. serum samples, simultaneous detection of ternary specific antigens can significantly improve the accuracy of liver cancer diagnosis.
- 242Gao, M.-Y.; Chen, Q.; Li, W.; Shen, A.-G.; Hu, J.-M. Combined Surface-Enhanced Raman Scattering Emissions for High-Throughput Optical Labels on Micrometer-Scale Objects. Anal. Chem. 2019, 91, 13866– 13873, DOI: 10.1021/acs.analchem.9b03357242Combined Surface-Enhanced Raman Scattering Emissions for High-Throughput Optical Labels on Micrometer-Scale ObjectsGao, Meng-Yue; Chen, Qiao; Li, Wei; Shen, Ai-Guo; Hu, Ji-MingAnalytical Chemistry (Washington, DC, United States) (2019), 91 (21), 13866-13873CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)High-throughput optical labeling technologies have become increasingly important with the growing demands for mol. detection, disease diagnosis, and drug discovery. In this thought, a series of CN-bridged coordination polymer encapsulated gold nanoparticles have been developed as a universal and interference-free optical label through a facile and auxiliary agent-free self-assembly route. Moreover, surface-enhanced Raman scattering (SERS) emissions of CN-bridge can be tuned flexibly by simple replacement of Fe2+/Fe3+ with other metal ions relying on synthesis of three Prussian blue analogs encapsulated gold nanoparticles (Au@PBA NPs). Thus, three distinct Raman frequencies have been acquired, merely replaced the metal irons. Based on the potential super-multiplex optical label, space-confined surface-enhanced Raman scattering (SERS) emissions has been realized. Relying on 'Abbe theorem', the focused laser allows the pure and single triple bond-coded SERS emissions being combined into a unique and independent output, so called 'combined SERS emission' (c-SERS), if the Au@PBA NPs were confined into one micron-scale object. This study demonstrated c-SERS may simultaneously provide 2n-1 optical labels only using n single emissions in Raman-silent region for micron-size objects.
- 243Zeng, Y.; Ren, J.; Shen, A.; Hu, J. Field and Pretreatment-Free Detection of Heavy-Metal Ions in Organic Polluted Water through an Alkyne-Coded SERS Test Kit. Acs Appl. Mater. Inter 2016, 8, 27772– 27778, DOI: 10.1021/acsami.6b09722There is no corresponding record for this reference.
- 244Zeng, Y.; Ren, J.-Q.; Wang, S.-K.; Mai, J.-M.; Qu, B.; Zhang, Y.; Shen, A.-G.; Hu, J.-M. Rapid and Reliable Detection of Alkaline Phosphatase by a Hot Spots Amplification Strategy Based on Well-Controlled Assembly on Single Nanoparticle. Acs Appl. Mater. Inter 2017, 9, 29547– 29553, DOI: 10.1021/acsami.7b09336There is no corresponding record for this reference.
- 245Zhang, Y.; Zou, Y.; Liu, F.; Xu, Y.; Wang, X.; Li, Y.; Liang, H.; Chen, L.; Chen, Z.; Tan, W. Stable Graphene-Isolated-Au-Nanocrystal for Accurate and Rapid Surface Enhancement Raman Scattering Analysis. Anal. Chem. 2016, 88, 10611– 10616, DOI: 10.1021/acs.analchem.6b02958245Stable Graphene-Isolated-Au-Nanocrystal for Accurate and Rapid Surface Enhancement Raman Scattering AnalysisZhang, Yin; Zou, Yuxiu; Liu, Fang; Xu, Yiting; Wang, Xuewei; Li, Yunjie; Liang, Hao; Chen, Long; Chen, Zhuo; Tan, WeihongAnalytical Chemistry (Washington, DC, United States) (2016), 88 (21), 10611-10616CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Various interferences from measurement conditions and substrate inhomogeneity are known confounding factors for poor reproducibility, which is a challenge in surface-enhanced Raman scattering (SERS) quantification. To address these issues, novel substrates and versatile internal stds. have been designed and the repeatability is improved to some degree. However, these internal stds. are either complex or unstable enough to resist harsh environments such as acid and oxidn. Graphene-isolated-Au-nanocrystal (GIAN) has unique properties and been applied for cell multimodal imaging and chemotherapy but not for SERS quantification anal. yet. Herein, the authors chose GIANs to improve the accuracy of SERS anal. GIAN integrates the SERS effect and internal std. into a simple nanoparticle and is an ideal platform for SERS anal. given its superior properties: (1) chem. stability, it remains stable in strong acid and oxidn., even mimic bioenvironment; (2) a simple core-shell structure, with a thin graphitic shell which is not only a protector that avoids inner Au catalysis unnecessary reaction but also an internal std. to eliminate the interference during the Raman detections; (3) the big-Π structure can absorb target mol. thus achieving an enrichment effect and quenching background fluorescence. Laser power, focus, and substrate fluctuations as well as coexist substance interferences were studied and the accuracy was improved greatly with the introduction of 2D band internal std. in Raman silent region with less background. Moreover, GIAN was applied for crystal violet detn. directly on fish muscle and scale, which was rapid and convenient without complex extn. process. All these results indicate GIAN is an optimum choice for SERS anal. in complex systems.
- 246Meng, X.; Wang, H.; Chen, N.; Ding, P.; Shi, H.; Zhai, X.; Su, Y.; He, Y. A Graphene–Silver Nanoparticle–Silicon Sandwich SERS Chip for Quantitative Detection of Molecules and Capture, Discrimination, and Inactivation of Bacteria. Anal. Chem. 2018, 90, 5646– 5653, DOI: 10.1021/acs.analchem.7b05139246A Graphene-Silver Nanoparticle-Silicon Sandwich SERS Chip for Quantitative Detection of Molecules and Capture, Discrimination, and Inactivation of BacteriaMeng, Xinyu; Wang, Houyu; Chen, Na; Ding, Pan; Shi, Huayi; Zhai, Xia; Su, Yuanyuan; He, YaoAnalytical Chemistry (Washington, DC, United States) (2018), 90 (9), 5646-5653CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)There currently exists increasing concerns on the development of a kind of high-performance SERS platform, which is suitable for sensing applications ranging from the mol. to cellular (e.g., bacteria) level. Herein, we develop a novel kind of universal SERS chip, made of graphene (G)-silver nanoparticle (AgNP)-silicon (Si) sandwich nanohybrids (G@AgNPs@Si), in which AgNPs are in situ grown on a silicon wafer through hydrofluoric acid-etching-assisted chem. redn., followed by coating with single-layer graphene via a polymer-protective etching method. The resultant chip features a strong, stable, reproducible surface-enhanced Raman scattering (SERS) effect and reliable quant. capability. By virtues of these merits, the G@AgNPs@Si platform is capable for not only mol. detection and quantification but also cellular anal. in real systems. As a proof-of-concept application, the chip allows ultrahigh sensitive and reliable detection of ATP, with a detection limit of ∼1 pM. In addn., the chip, serving as a novel multifunctional platform, enables simultaneous capture, discrimination, and inactivation of bacteria. Typically, the bacterial capture efficiency is 54% at 108 CFU mL-1 bacteria, and the antibacterial rate reaches 93% after 24 h of treatment. Of particular note, Escherichia coli and Staphylococcus aureus spiked into blood can be readily distinguished via the chip, suggesting its high potential for clin. applications.
- 247Yin, Y.; Li, Q.; Ma, S.; Liu, H.; Dong, B.; Yang, J.; Liu, D. Prussian Blue as a Highly Sensitive and Background-Free Resonant Raman Reporter. Anal. Chem. 2017, 89, 1551– 1557, DOI: 10.1021/acs.analchem.6b03521247Prussian Blue as a Highly Sensitive and Background-Free Resonant Raman ReporterYin, Yongmei; Li, Qiang; Ma, Sisi; Liu, Huiqiao; Dong, Bo; Yang, Jie; Liu, DingbinAnalytical Chemistry (Washington, DC, United States) (2017), 89 (3), 1551-1557CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)The authors report a surprising discovery that Prussian blue (PB) can be employed as a highly sensitive and background-free resonant Raman reporter. Conventional Raman reporters show multiple spectral bands in the fingerprint region, which are generally overlapped with those from dominant endogenous biomols., and are thus difficult to be sepd. Herein, PB only possesses a strong and sharp single-band in the cellular Raman-silent region, where no Raman signals from biol. species were obsd. Therefore, the Raman spectra from PB and endogenous biomols. are completely resolved without resorting to complicated spectral unmixing. Moreover, PB holds a strong UV-visible absorption band between 500 and 900 nm, which is resonant with the incident detection lasers, providing extremely high sensitivity. Through assembly of PB onto plasmonic cores, a new surface-enhanced resonance Raman scattering (SERRS) probe was achieved with a high signal-to-background ratio (SBR). The authors demonstrated the performance of the PB-based SERRS tags for high-sensitivity immunoassay and cancer cell imaging.
- 248Li, J.; Liu, F.; Ye, J. Boosting the Brightness of Thiolated Surface-Enhanced Raman Scattering Nanoprobes by Maximal Utilization of the Three-Dimensional Volume of Electromagnetic Fields. J. Phys. Chem. Lett. 2022, 13, 6496– 6502, DOI: 10.1021/acs.jpclett.2c01741There is no corresponding record for this reference.
- 249Li, J.; Liu, F.; Bi, X.; Ye, J. Imaging immune checkpoint networks in cancer tissues with supermultiplexed SERS nanoprobes. Biomaterials 2023, 302, 122327, DOI: 10.1016/j.biomaterials.2023.122327There is no corresponding record for this reference.
- 250Smith, A. M.; Mancini, M. C.; Nie, S. Second window for in vivo imaging. Nat. Nanotechnol. 2009, 4, 710– 711, DOI: 10.1038/nnano.2009.326250Second window for in vivo imagingSmith, Andrew M.; Mancini, Michael C.; Nie, ShumingNature Nanotechnology (2009), 4 (11), 710-711CODEN: NNAABX; ISSN:1748-3387. (Nature Publishing Group)Enhanced fluorescence from carbon nanotubes and advances in near-IR cameras have opened up a new wavelength window for small animal imaging.
- 251Kenry; Duan, Y.; Liu, B. Recent Advances of Optical Imaging in the Second Near-Infrared Window. Adv. Mater. 2018, 30, 1802394, DOI: 10.1002/adma.201802394There is no corresponding record for this reference.
- 252Deng, B.; Zhang, Y.; Qiu, G.; Li, J.; Lin, L. L.; Ye, J. NIR-II Surface-Enhanced Raman Scattering Nanoprobes in Biomedicine: Current Impact and Future Directions. Small 2024, 2402235, DOI: 10.1002/smll.202402235There is no corresponding record for this reference.
- 253Lane, L. A.; Xue, R.; Nie, S. Emergence of two near-infrared windows for in vivo and intraoperative SERS. Curr. Opin. Chem. Biol. 2018, 45, 95– 103, DOI: 10.1016/j.cbpa.2018.03.015253Emergence of two near-infrared windows for in vivo and intraoperative SERSLane, Lucas A.; Xue, Ruiyang; Nie, ShumingCurrent Opinion in Chemical Biology (2018), 45 (), 95-103CODEN: COCBF4; ISSN:1367-5931. (Elsevier B.V.)A review. Two clear windows in the near-IR (NIR) spectrum are of considerable current interest for in vivo mol. imaging and spectroscopic detection. The main rationale is that near-IR light can penetrate biol. tissues such as skin and blood more efficiently than visible light because these tissues scatter and absorb less light at longer wavelengths. The first clear window, defined as light wavelengths between 650 nm and 950 nm, has been shown to be far superior for in vivo and intraoperative optical imaging than visible light. The second clear window, operating in the wavelength range of 1000-1700 nm, has been reported to further improve detection sensitivity, spatial resoln., and tissue penetration because tissue photon scattering and background interference are further reduced at longer wavelengths. Here we discuss recent advances in developing biocompatible plasmonic nanoparticles for in vivo and intraoperative surface-enhanced Raman scattering (SERS) in both the first and second NIR windows. In particular, a new class of 'broad-band' plasmonic nanostructures is well suited for surface Raman enhancement across a broad range of wavelengths allowing a direct comparison of detection sensitivity and tissue penetration between the two NIR window. Also, optimized and encoded SERS nanoparticles are generally nontoxic and are much brighter than near-IR quantum dots (QDs), raising new possibilities for ultrasensitive detection of microscopic tumors and image-guided precision surgery.
- 254Antaris, A. L.; Chen, H.; Cheng, K.; Sun, Y.; Hong, G.; Qu, C.; Diao, S.; Deng, Z.; Hu, X.; Zhang, B.; Zhang, X.; Yaghi, O. K.; Alamparambil, Z. R.; Hong, X.; Cheng, Z.; Dai, H. A small-molecule dye for NIR-II imaging. Nat. Mater. 2016, 15, 235– 242, DOI: 10.1038/nmat4476254A small-molecule dye for NIR-II imagingAntaris, Alexander L.; Chen, Hao; Cheng, Kai; Sun, Yao; Hong, Guosong; Qu, Chunrong; Diao, Shuo; Deng, Zixin; Hu, Xianming; Zhang, Bo; Zhang, Xiaodong; Yaghi, Omar K.; Alamparambil, Zita R.; Hong, Xuechuan; Cheng, Zhen; Dai, HongjieNature Materials (2016), 15 (2), 235-242CODEN: NMAACR; ISSN:1476-1122. (Nature Publishing Group)Fluorescent imaging of biol. systems in the second near-IR window (NIR-II) can probe tissue at centimetre depths and achieve micrometre-scale resoln. at depths of millimetres. Unfortunately, all current NIR-II fluorophores are excreted slowly and are largely retained within the reticuloendothelial system, making clin. translation nearly impossible. Here, we report a rapidly excreted NIR-II fluorophore (∼90% excreted through the kidneys within 24 h) based on a synthetic 970-Da org. mol. (CH1055). The fluorophore outperformed indocyanine green (ICG)-a clin. approved NIR-I dye-in resolving mouse lymphatic vasculature and sentinel lymphatic mapping near a tumor. High levels of uptake of PEGylated-CH1055 dye were obsd. in brain tumors in mice, suggesting that the dye was detected at a depth of ∼4 mm. The CH1055 dye also allowed targeted mol. imaging of tumors in vivo when conjugated with anti-EGFR Affibody. Moreover, a superior tumor-to-background signal ratio allowed precise image-guided tumor-removal surgery.
- 255Shan, B.; Pu, Y.; Chen, Y.; Liao, M.; Li, M. Novel SERS labels: Rational design, functional integration and biomedical applications. Coord. Chem. Rev. 2018, 371, 11– 37, DOI: 10.1016/j.ccr.2018.05.007255Novel SERS labels: Rational design, functional integration and biomedical applicationsShan, Beibei; Pu, Yuhan; Chen, Yingfan; Liao, Mengling; Li, MingCoordination Chemistry Reviews (2018), 371 (), 11-37CODEN: CCHRAM; ISSN:0010-8545. (Elsevier B.V.)Driven by the growing demand for healthcare and point-of-care test applications, next-generation diagnostic tools of diseases require sensing platforms that enable rapid, quant. readout of analytes with excellent specificity and sensitivity. Although label-free detection permits simplicity, flexibility and high specificity, it has usually poor throughput, limited sensitivity and requires professional instrumentation. Label-based detection using optical labels overcomes many of these drawbacks and has been demonstrated to be an effective alternative for improved sensing performances. The current research focus has been directed towards innovating high-performance optical labels for ultrasensitive biosensing and disease diagnostics in place of conventional optical labels. Surface-enhanced Raman scattering (SERS) labels have proven to be excellent labels for biosensing because of their merits in many aspects, such as flexibility, less interference from biol. matrixes, high photostability, easy multiplex encoding, etc. These fantastic features make SERS labels particularly suitable for ultrasensitive detection of disease biomarkers in body fluids and targeted imaging of diseased cells and tissues, resp. In this Review, we introduce the design and deployment of SERS labels for ultrasensitive detection, and summarize recent research progress in the development of SERS label-based sensing platforms and their applications in disease biomarker detection, targeted cellular imaging and spectroscopic detection of tumor lesions. First, we will discuss the design principles and comprehensive considerations of SERS labels, and the on-demand integration of functionalities. Next, we introduce the design of SERS sensing platforms on basis of SERS labels for ultrasensitive and selective detection of diverse pathol.-related biomarkers, including proteins, nucleic acids, small mols. and inorg. ions. In addn., through the rational incorporation of targeting ligands on SERS labels, novel SERS probes are created for targeting near-IR (NIR) imaging and spectroscopic detection of tumor, taking advantages of large NIR light penetration depth, high brightness, stability, etc. Our and other research efforts have demonstrated the promising potential of SERS label-based sensing platforms for detection of diverse circulating biomarkers for non-invasive disease diagnostics and deep-tissue spectroscopic detection of tumor. It is believed that this review will motivate further exploration of clin. applications of SERS labels in near future.
- 256Reguera, J.; Langer, J.; Jiménez de Aberasturi, D.; Liz-Marzán, L. M. Anisotropic metal nanoparticles for surface enhanced Raman scattering. Chem. Soc. Rev. 2017, 46, 3866– 3885, DOI: 10.1039/C7CS00158D256Anisotropic metal nanoparticles for surface enhanced Raman scatteringReguera, Javier; Langer, Judith; Jimenez de Aberasturi, Dorleta; Liz-Marzan, Luis M.Chemical Society Reviews (2017), 46 (13), 3866-3885CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)The optimization of the enhancement of Raman scattering by plasmonic effects is largely detd. by the properties of the enhancing substrates. The main parameters behind this effect are related to the morphol. of plasmonic nanoparticles and their relative distribution within the substrate. We focus this tutorial review on the effects of nanoparticle morphol., for the particular case of anisotropic metal nanoparticles. Anisotropy in silver and gold nanoparticles offers the possibility to tailor their plasmonic properties and intrinsic electromagnetic "hotspots". We describe the effect of varying particle size and shape on the SERS signal, focusing on the most common anisotropic morphologies used for SERS. Especial emphasis is made on existing comparative studies that shed light on the effect of nanoparticle anisotropy on their enhancement capabilities. We aim at providing a general perspective toward understanding the general key factors and highlighting the difficulty in quant. detg. SERS performance.
- 257He, H.; Zhang, Y.; Zhu, S.; Ye, J.; Lin, L. Resonant Strategy in Designing NIR-II SERS Nanotags: A Quantitative Study. J. Phys. Chem. C 2022, 126, 12575– 12581, DOI: 10.1021/acs.jpcc.2c02512There is no corresponding record for this reference.
- 258Chen, Y.-S.; Zhao, Y.; Yoon, S. J.; Gambhir, S. S.; Emelianov, S. Miniature gold nanorods for photoacoustic molecular imaging in the second near-infrared optical window. Nat. Nanotechnol. 2019, 14, 465– 472, DOI: 10.1038/s41565-019-0392-3258Miniature gold nanorods for photoacoustic molecular imaging in the second near-infrared optical windowChen, Yun-Sheng; Zhao, Yang; Yoon, Soon Joon; Gambhir, Sanjiv Sam; Emelianov, StanislavNature Nanotechnology (2019), 14 (5), 465-472CODEN: NNAABX; ISSN:1748-3387. (Nature Research)In photoacoustic imaging, the second near-IR (NIR-II) window is where tissue generates the least background signal. However, the large size of the few available contrast agents in this spectral range impedes their pharmacokinetics and decreases their thermal stability, leading to unreliable photoacoustic imaging. Here, the authors report the synthesis of miniaturized gold nanorods absorbing in the NIR-II that are 5-11 times smaller than regular-sized gold nanorods with a similar aspect ratio. Under nanosecond pulsed laser illumination, small nanorods are ∼3 times more thermally stable and generate 3.5 times stronger photoacoustic signal than their absorption-matched larger counterparts. These unexpected findings are confirmed using theor. and numerical anal., showing that photoacoustic signal is not only proportional to the optical absorption of the nanoparticle soln. but also to the surface-to-vol. ratio of the nanoparticles. In living tumor-bearing mice, these small targeted nanorods display a 30% improvement in efficiency of agent delivery to tumors and generate 4.5 times greater photoacoustic contrast.
- 259Tsai, M.-F.; Chang, S.-H. G.; Cheng, F.-Y.; Shanmugam, V.; Cheng, Y.-S.; Su, C.-H.; Yeh, C.-S. Au Nanorod Design as Light-Absorber in the First and Second Biological Near-Infrared Windows for in Vivo Photothermal Therapy. ACS Nano 2013, 7, 5330– 5342, DOI: 10.1021/nn401187c259Au Nanorod Design as Light-Absorber in the First and Second Biological Near-Infrared Windows for in Vivo Photothermal TherapyTsai, Ming-Fong; Chang, Shih-Hui Gilbert; Cheng, Fong-Yu; Shanmugam, Vijayakumar; Cheng, Yu-Sheng; Su, Chia-Hao; Yeh, Chen-ShengACS Nano (2013), 7 (6), 5330-5342CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Photothermal cancer therapy using near-IR (NIR) laser radiation is an emerging treatment. In the NIR region, two biol. transparency windows are located in 650-950 nm (first NIR window) and 1000-1350 nm (second NIR window) with optimal tissue transmission obtained from low scattering and energy absorption, thus providing max. radiation penetration through tissue and minimizing autofluorescence. To date, intensive effort has resulted in the generation of various methods that can be used to shift the absorbance of nanomaterials to the 650-950 nm NIR regions for studying photoinduced therapy. However, NIR light absorbers smaller than 100 nm in the second NIR region have been scant. We report that a Au nanorod (NR) can be designed with a rod-in-shell (rattle-like) structure smaller than 100 nm that is tailored to be responsive to the first and second NIR windows, in which we can perform hyperthermia-based therapy. In vitro performance clearly displays high efficacy in the NIR photothermal destruction of cancer cells, showing large cell-damaged area beyond the laser-irradiated area. This marked phenomenon has made the rod-in-shell structure a promising hyperthermia agent for the in vivo photothermal ablation of solid tumors when activated using a continuous-wave 808 m (first NIR window) or a 1064 nm (second NIR window) diode laser. We tailored the UV-vis-NIR spectrum of the rod-in-shell structure by changing the gap distance between the Au NR core and the AuAg nanoshell, to evaluate the therapeutic effect of using a 1064 nm diode laser. Regarding the first NIR window with the use of an 808 nm diode laser, rod-in-shell particles exhibit a more effective anticancer efficacy in the laser ablation of solid tumors compared to Au NRs.
- 260Skrabalak, S. E.; Au, L.; Li, X.; Xia, Y. Facile synthesis of Ag nanocubes and Au nanocages. Nat. Protoc 2007, 2, 2182– 2190, DOI: 10.1038/nprot.2007.326260Facile synthesis of Ag nanocubes and Au nanocagesSkrabalak, Sara E.; Au, Leslie; Li, Xingde; Xia, YounanNature Protocols (2007), 2 (9), 2182-2190CODEN: NPARDW; ISSN:1750-2799. (Nature Publishing Group)This protocol describes a method for the synthesis of Ag nanocubes and their subsequent conversion into Au nanocages via the galvanic replacement reaction. The Ag nanocubes were prepd. by a rapid (reaction time < 15 min), sulfide-mediated polyol method in which Ag(I) is reduced to Ag(0) by ethylene glycol in the presence of poly(vinyl pyrrolidone) (PVP) and a trace amt. of Na2S. When the concn. of Ag atoms reaches supersatn., they agglomerate to form seeds that then grow into Ag nanostructures. The presence of both PVP and Na2S facilitate the formation of nanocubes. With this method, Ag nanocubes can be prepd. and isolated for use within ∼3 h. The Ag nanocubes can then serve as sacrificial templates for the prepn. of Au nanocages, with a method for their prepn. also described herein. The procedure for Au nanocage prepn. and isolation requires ∼5 h.
- 261Shan, B.; Li, L.; Zhao, Y.; Wang, H.; Li, M. Near-Infrared II Plasmonic Au@Au–Ag Dot-in-Cubic Nanoframes for In Vivo Surface-Enhanced Raman Spectroscopic Detection and Photoacoustic Imaging. Adv. Funct. Mater. 2021, 31, 2103186, DOI: 10.1002/adfm.202103186261Near-Infrared II Plasmonic Au@Au-Ag Dot-in-Cubic Nanoframes for In Vivo Surface-Enhanced Raman Spectroscopic Detection and Photoacoustic ImagingShan, Beibei; Li, Linhu; Zhao, Yawen; Wang, Haitao; Li, MingAdvanced Functional Materials (2021), 31 (29), 2103186CODEN: AFMDC6; ISSN:1616-301X. (Wiley-VCH Verlag GmbH & Co. KGaA)Near-IR II (NIR-II) plasmonic noble-metallic nanostructures are highly desirable for in vivo photodiagnostics because of their multiple functionalities and deep-tissue optical imaging capability. Herein, a novel class of Au@Au-Ag dot-in-cubic nanoframes (DCFs) comprising a solid Au core and a Au-Ag alloy shell with a wall hole on each side face is reported, which exhibit remarkable plasmonic properties spectrally tunable beyond 1400 nm while maintaining a small size. The synthesis of Au@Au-Ag DCFs is principally based on the facet-selective etching of Ag atoms and co-deposition of Au and Ag atoms on the edges and corners of Au@Ag dot-in-cubes. The geometry (e.g., edge length and wall hole size) can be controllably tailored by simply varying the silver nitrate and chloroauric acid concns. Superior in vitro and in vivo NIR-II photoacoustic imaging performances of Au@Au-Ag DCFs are demonstrated. Addnl., remarkable NIR-II surface-enhanced Raman spectroscopy (SERS) activity of Au@Au-Ag DCFs is evidenced with the max. NIR-II SERS enhancement occurring at a plasmon resonance wavelength blue-shifting from the incident laser wavelength and an excellent effective detection depth. Finally, the potential of the developed Au@Au-Ag DCFs is highlighted for in vivo NIR-II SERS detection of microtumors in animals.
- 262Li, L.; Jiang, R.; Shan, B.; Lu, Y.; Zheng, C.; Li, M. Near-infrared II plasmonic porous cubic nanoshells for in vivo noninvasive SERS visualization of sub-millimeter microtumors. Nat. Commun. 2022, 13, 5249, DOI: 10.1038/s41467-022-32975-w262Near-infrared II plasmonic porous cubic nanoshells for in vivo noninvasive SERS visualization of sub-millimeter microtumorsLi, Linhu; Jiang, Renting; Shan, Beibei; Lu, Yaxuan; Zheng, Chao; Li, MingNature Communications (2022), 13 (1), 5249CODEN: NCAOBW; ISSN:2041-1723. (Nature Portfolio)In vivo surface-enhanced Raman scattering (SERS) imaging allows non-invasive visualization of tumors for intraoperative guidance and clin. diagnostics. However, the in vivo utility of SERS is greatly hampered by the strong optical scattering and autofluorescence background of biol. tissues and the lack of highly active plasmonic nanostructures. Herein, we report a class of porous nanostructures comprising a cubic AuAg alloy nanoshell and numerous nanopores. Such porous nanostructures exhibit excellent near-IR II plasmonic properties tunable in a broad spectral range by varying the pore features while maintaining a small dimension. We demonstrate their exceptional near-IR II SERS performance varying with the porous properties. Addnl., near-IR II SERS probes created with porous cubic AuAg nanoshells are demonstrated with remarkable capability for in vivo visualization of sub-millimeter microtumors in a living mouse model. Our near-IR II SERS probes hold great potentials for precise demarcation of tumor margins and identification of microscopic tumors.
- 263Deng, B.; Wang, Y.; Bu, X.; Li, J.; Lu, J.; Lin, L. L.; Wang, Y.; Chen, Y.; Ye, J. Sentinel lymph node identification using NIR-II ultrabright Raman nanotags on preclinical models. Biomaterials 2024, 308, 122538, DOI: 10.1016/j.biomaterials.2024.122538There is no corresponding record for this reference.
- 264Lu, Y.; Li, M. Rational Design of Near-infrared II Plasmonic Optofunctional Materials for Diagnostic and Therapeutic Applications. Adv. Funct. Mater. 2024, 34, 2312753, DOI: 10.1002/adfm.202312753There is no corresponding record for this reference.
- 265Li, J.; Deng, B.; Ye, J. Fluorescence-free bis(dithiolene)nickel dyes for surface-enhanced resonance Raman imaging in the second near-infrared window. Biomaterials 2023, 300, 122211, DOI: 10.1016/j.biomaterials.2023.122211There is no corresponding record for this reference.
- 266Tian, Y.-F.; Zhou, W.; Yin, B.-C.; Ye, B.-C. Highly sensitive surface-enhanced Raman scattering detection of adenosine triphosphate based on core–satellite assemblies. Analytical Methods 2017, 9, 6038– 6043, DOI: 10.1039/C7AY02096AThere is no corresponding record for this reference.
- 267Wang, Y.; Salehi, M.; Schütz, M.; Rudi, K.; Schlücker, S. Microspectroscopic SERS detection of interleukin-6 with rationally designed gold/silver nanoshells. Analyst 2013, 138, 1764– 1771, DOI: 10.1039/c3an36610c267Microspectroscopic SERS detection of interleukin-6 with rationally designed gold/silver nanoshellsWang, Yuling; Salehi, Mohammad; Schuetz, Max; Rudi, Katharina; Schluecker, SebastianAnalyst (Cambridge, United Kingdom) (2013), 138 (6), 1764-1771CODEN: ANALAO; ISSN:0003-2654. (Royal Society of Chemistry)Rationally designed gold/silver nanoshells (Au/Ag-NS) with plasmon resonances optimized for red laser excitation in order to minimize autofluorescence from clin. samples exhibit scattering cross-sections, which are ca. one order of magnitude larger compared with solid quasi-spherical gold nanoparticles (Au-NPs) of the same size. Hydrophilic stabilization and sterical accessibility for subsequent bioconjugation of Au/Ag-NS is achieved by coating their surface with a self-assembled monolayer (SAM) of rationally designed Raman reporter mols. comprising terminal mono- and tri-ethylene glycol (EG) spacers, resp. The stability of the hydrophilically stabilized metal colloid was tested under different conditions. In contrast to metal colloids coated with a SAM without terminal EG spacers, the hydrophilically stabilized SERS particles do not aggregate under physiol. relevant conditions, i.e., buffer solns. with high ionic strength. Using these rationally designed SERS particles in conjunction with a microspectroscopic acquisition scheme, a sandwich immunoassay for the sensitive detection of interleukin-6 (IL-6) was developed. Several control expts. demonstrate the high specificity of the assay towards IL-6, with a lowest detectable concn. of ca. 1 pg mL-1. The signal strength of the Au/Ag-NS is at least one order of magnitude higher compared with hydrophilically stabilized, non-aggregated solid quasi-spherical Au-NPs of the same size.
- 268Wang, H.; Wang, Y.; Yuan, C.; Xu, X.; Zhou, W.; Huang, Y.; Lu, H.; Zheng, Y.; Luo, G.; Shang, J.; Sui, M. Polyethylene glycol (PEG)-associated immune responses triggered by clinically relevant lipid nanoparticles in rats. NPJ. Vaccines 2023, 8, 169, DOI: 10.1038/s41541-023-00766-zThere is no corresponding record for this reference.
- 269Bodelón, G.; Montes-García, V.; Fernández-López, C.; Pastoriza-Santos, I.; Pérez-Juste, J.; Liz-Marzán, L. M. Au@pNIPAM SERRS Tags for Multiplex Immunophenotyping Cellular Receptors and Imaging Tumor Cells. Small 2015, 11, 4149– 4157, DOI: 10.1002/smll.201500269269Au@pNIPAM SERRS Tags for Multiplex Immunophenotyping Cellular Receptors and Imaging Tumor CellsBodelon, Gustavo; Montes-Garcia, Veronica; Fernandez-Lopez, Cristina; Pastoriza-Santos, Isabel; Perez-Juste, Jorge; Liz-Marzan, Luis M.Small (2015), 11 (33), 4149-4157CODEN: SMALBC; ISSN:1613-6810. (Wiley-VCH Verlag GmbH & Co. KGaA)Detection technologies employing optically encoded particles have gained much interest toward clin. diagnostics and drug discovery, but the portfolio of available systems is still limited. The fabrication and characterization of highly stable surface-enhanced resonance Raman scattering (SERRS)-encoded colloids for the identification and imaging of proteins expressed in cells are reported. These plasmonic nanostructures are made of gold octahedra coated with poly(N-isopropylacrylamide) microgels and can be readily encoded with Raman active dyes while retaining high colloidal stability in biofluids. A layer-by-layer polyelectrolyte coating was used to seal the outer surface of the encoded particles and to provide a reactive surface for covalent conjugation with antibodies. The targeted multiplexing capabilities of the SERRS tags are demonstrated by the simultaneous detection and imaging of three tumor-assocd. surface biomarkers: epidermal growth factor receptor (EGFR), epithelial cell adhesion mol. (EpCAM), and homing cell adhesion mol. (CD44) by SERRS spectroscopy. The plasmonic microgels are able to discriminate tumor A431 (EGFR+/EpCAM+/CD44+) and nontumor 3T3 2.2 (EGFR-/EpCAM-/CD44+) cells while cocultured in vitro.
- 270Casado-Rodriguez, M. A.; Sanchez-Molina, M.; Lucena-Serrano, A.; Lucena-Serrano, C.; Rodriguez-Gonzalez, B.; Algarra, M.; Diaz, A.; Valpuesta, M.; Lopez-Romero, J. M.; Perez-Juste, J.; Contreras-Caceres, R. Synthesis of vinyl-terminated Au nanoprisms and nanooctahedra mediated by 3-butenoic acid: direct Au@pNIPAM fabrication with improved SERS capabilities. Nanoscale 2016, 8, 4557– 4564, DOI: 10.1039/C5NR08054A270Synthesis of vinyl-terminated Au nanoprisms and nanooctahedra mediated by 3-butenoic acid: direct Au@pNIPAM fabrication with improved SERS capabilitiesCasado-Rodriguez, M. A.; Sanchez-Molina, M.; Lucena-Serrano, A.; Lucena-Serrano, C.; Rodriguez-Gonzalez, B.; Algarra, M.; Diaz, A.; Valpuesta, M.; Lopez-Romero, J. M.; Perez-Juste, J.; Contreras-Caceres, R.Nanoscale (2016), 8 (8), 4557-4564CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)Here we describe the first seedless synthesis of vinyl-terminated Au nanotriangular prisms (AuNTPs) and nanooctahedra (AuNOC) in aq. media. This synthesis is performed by chem. redn. of chloroauric acid (HAuCl4) with 3-butenoic acid (3BA) in the presence of benzyldimethylammonium chloride (BDAC). The principal novelties of the presented method are the use of a mixt. of 3BA and BDAC, the synthesis of gold prisms and octahedra with controllable size, and the presence of terminal double bonds on the metal surface. Initially this method produces a mixt. of triangular gold nanoprisms and octahedra; however, both morphologies are successfully sepd. by surfactant micelle induced depletion interaction, reaching percentages up to~ 90%. Moreover, the alkene moieties present on the gold surface are exploited for the fabrication of hybrid core@shell particles. Gold octahedra and triangular prisms are easily encapsulated by free radical polymn. of N-isopropylacrylamide (NIPAM). Finally, in order to obtain a gold core with the most no. of tips, AuNTP@pNIPAM microgels were subjected to gold core overgrowth, thus resulting in star-shaped nanoparticles (AuSTs@pNIPAM). We use 4-amino-benzenethiol as the model analyte for SERS investigations. As expected, gold cores with tips and high curvature sites produced the highest plasmonic responses.
- 271Yokota, K.; Usuda, S.; Nishimura, N.; Takahashi, R.; Taoka, Y.; Kobayashi, S.; Tanaka, M.; Matsumura, K.; Yusa, S.-I. Self-Assembly and Drug Encapsulation Properties of Biocompatible Amphiphilic Diblock Copolymers. Langmuir 2025, 41 (1), 765– 773, DOI: 10.1021/acs.langmuir.4c04048There is no corresponding record for this reference.
- 272Alipour, E.; Halverson, D.; McWhirter, S.; Walker, G. C. Phospholipid Bilayers: Stability and Encapsulation of Nanoparticles. Annu. Rev. Phys. Chem. 2017, 68, 261– 283, DOI: 10.1146/annurev-physchem-040215-112634272Phospholipid Bilayers: Stability and Encapsulation of NanoparticlesAlipour, Elnaz; Halverson, Duncan; McWhirter, Samantha; Walker, Gilbert C.Annual Review of Physical Chemistry (2017), 68 (), 261-283CODEN: ARPLAP; ISSN:0066-426X. (Annual Reviews)Nanoparticles are widely studied for their potential medical uses in diagnostics and therapeutics. The interface between a nanoparticle and its target has been a focus of research, both to guide the nanoparticle and to prevent it from deactivating. Given nature's frequent use of phospholipid vesicles as carriers, much attention has been paid to phospholipids as a vehicle for drug delivery. The phys. chem. of bilayer formation and nanoparticle encapsulation is complex, touching on fundamental properties of hydrophobicity. Understanding the design rules for particle synthesis and encapsulation is an active area of research. The aim of this review is to provide a perspective on what preparative guideposts have been empirically discovered and how these are related to theor. understanding. In addn., we aim to summarize how modern theory is beginning to help guide the design of functional particles that can effectively cross biol. membranes.
- 273Bruzas, I.; Brinson, B. E.; Gorunmez, Z.; Lum, W.; Ringe, E.; Sagle, L. Surface-Enhanced Raman Spectroscopy of Fluid-Supported Lipid Bilayers. ACS Appl. Mater. & Interfaces 2019, 11, 33442– 33451, DOI: 10.1021/acsami.9b09988There is no corresponding record for this reference.
- 274Tam, N. C.; McVeigh, P. Z.; MacDonald, T. D.; Farhadi, A.; Wilson, B. C.; Zheng, G. Porphyrin-lipid stabilized gold nanoparticles for surface enhanced Raman scattering based imaging. Bioconjugate Chem. 2012, 23, 1726– 30, DOI: 10.1021/bc300214z274Porphyrin-Lipid Stabilized Gold Nanoparticles for Surface Enhanced Raman Scattering Based ImagingTam, Natalie C. M.; McVeigh, Patrick Z.; MacDonald, Thomas D.; Farhadi, Arash; Wilson, Brian C.; Zheng, GangBioconjugate Chemistry (2012), 23 (9), 1726-1730CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)A porphyrin-phospholipid conjugate with quenched fluorescence was utilized to serve as both the Raman dye and a stabilizing, biocompatible surface coating agent on gold nanoparticles. Through simple synthesis and validation with spectroscopy and confocal microscopy, it was shown that this porphyrin-phospholipid stabilized AuNP is a novel SERS probe capable of cellular imaging. To date, this is the first use of porphyrin as a Raman reporter mol. for SERS based imaging.
- 275Zheng, X.-S.; Hu, P.; Cui, Y.; Zong, C.; Feng, J.-M.; Wang, X.; Ren, B. BSA-Coated Nanoparticles for Improved SERS-Based Intracellular pH Sensing. Anal. Chem. 2014, 86, 12250– 12257, DOI: 10.1021/ac503404u275BSA-Coated Nanoparticles for Improved SERS-Based Intracellular pH SensingZheng, Xiao-Shan; Hu, Pei; Cui, Yan; Zong, Cheng; Feng, Jia-Min; Wang, Xin; Ren, BinAnalytical Chemistry (Washington, DC, United States) (2014), 86 (24), 12250-12257CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Local microenvironment pH sensing is one of the key parameters for the understanding of many biol. processes. As a noninvasive and high sensitive technique, surface-enhanced Raman spectroscopy (SERS) has attracted considerable interest in the detection of the local pH of live cells. We herein develop a facile way to prep. Au-(4-MPy)-BSA (AMB) pH nanosensor. The 4-MPy (4-mercaptopyridine) was used as the pH sensing mol. The modification of the nanoparticles with BSA not only provides a high sensitive response to pH changes ranging from pH 4.0 to 9.0 but also exhibits a high sensitivity and good biocompatibility, stability, and reliability in various solns. (including the solns. of high ionic strength or with complex compn. such as the cell culture medium), both in the aggregation state or after long-term storage. The AMB pH nanosensor shows great advantages for reliable intracellular pH anal. and has been successfully used to monitor the pH distribution of live cells and can address the grand challenges in SERS-based pH sensing for practical biol. applications.
- 276Blanco-Covián, L.; Montes-García, V.; Girard, A.; Fernández-Abedul, M. T.; Pérez-Juste, J.; Pastoriza-Santos, I.; Faulds, K.; Graham, D.; Blanco-López, M. C. Au@Ag SERRS tags coupled to a lateral flow immunoassay for the sensitive detection of pneumolysin. Nanoscale 2017, 9, 2051– 2058, DOI: 10.1039/C6NR08432J276Au@Ag SERRS tags coupled to a lateral flow immunoassay for the sensitive detection of pneumolysinBlanco-Covian, Lucia; Montes-Garcia, Veronica; Girard, Alexandre; Fernandez-Abedul, M. Teresa; Perez-Juste, Jorge; Pastoriza-Santos, Isabel; Faulds, Karen; Graham, Duncan; Blanco-Lopez, M. CarmenNanoscale (2017), 9 (5), 2051-2058CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)Establishing a definitive diagnosis of pneumonia using conventional tests is difficult and expensive. Lateral flow immunoassays (LFIAs) are an advantageous point of care (POC) test option, but they have some limitations in terms of detection and quantification. In this work we have developed a lateral flow immunoassay for the ultrasensitive detection of penumolysin employing plasmonic Surface-Enhanced Resonance Raman Scattering (SERRS) tag as labeled probe. The combination of Au@Ag core-shell nanoparticles as plasmonic platform and Rhodamine B Isothiocyanate as Raman reporter has allowed us to fabricate a SERRS tag with high efficiency and reliability. The limit of detection of the SERRS-based LFIA was 1 pg mL-1. This could be a strong foundation for a pneumonia diagnosis test based on pneumolysin detection.
- 277Sun, L.; Sung, K.-B.; Dentinger, C.; Lutz, B.; Nguyen, L.; Zhang, J.; Qin, H.; Yamakawa, M.; Cao, M.; Lu, Y.; Chmura, A. J.; Zhu, J.; Su, X.; Berlin, A. A.; Chan, S.; Knudsen, B. Composite Organic–Inorganic Nanoparticles as Raman Labels for Tissue Analysis. Nano Lett. 2007, 7, 351– 356, DOI: 10.1021/nl062453t277Composite Organic-Inorganic Nanoparticles as Raman Labels for Tissue AnalysisSun, Lei; Sung, Kung-Bin; Dentinger, Claire; Lutz, Barry; Nguyen, Lienchi; Zhang, Jingwu; Qin, Haoyu; Yamakawa, Mineo; Cao, Manqiu; Lu, Yu; Chmura, Aj; Zhu, Jing; Su, Xing; Berlin, Andrew A.; Chan, Selena; Knudsen, BeatriceNano Letters (2007), 7 (2), 351-356CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)Composite org.-inorg. nanoparticles (COINs) are novel optical labels for detection of biomols. The authors have previously developed methods to encapsulate COINs and to functionalize them with antibodies. Here the authors report the first steps toward application of COINs to the detection of proteins in human tissues. Two analytes, PSA and CK18, are detected simultaneously using two different COINs in a direct binding assay, and two different COINs are shown to simultaneously label PSA in tissue samples.
- 278Küstner, B.; Gellner, M.; Schütz, M.; Schöppler, F.; Marx, A.; Ströbel, P.; Adam, P.; Schmuck, C.; Schlücker, S. SERS labels for red laser excitation: silica-encapsulated SAMs on tunable gold/silver nanoshells. Angew. Chem., Int. Ed 2009, 48, 1950– 1953, DOI: 10.1002/anie.200804518There is no corresponding record for this reference.
- 279Wang, C.; Yan, Q.; Liu, H.-B.; Zhou, X.-H.; Xiao, S.-J. Different EDC/NHS Activation Mechanisms between PAA and PMAA Brushes and the Following Amidation Reactions. Langmuir 2011, 27, 12058– 12068, DOI: 10.1021/la202267p279Different EDC/NHS Activation Mechanisms between PAA and PMAA Brushes and the Following Amidation ReactionsWang, Cuie; Yan, Qin; Liu, Hong-Bo; Zhou, Xiao-Hui; Xiao, Shou-JunLangmuir (2011), 27 (19), 12058-12068CODEN: LANGD5; ISSN:0743-7463. (American Chemical Society)IR spectroscopy was applied to investigate the well-known EDC/NHS (N-ethyl-N'-(3-(dimethylamino)propyl)carbodiimide/N-hydroxysuccinimide) activation details of poly(acrylic acid) (PAA) and poly(methacrylic acid) (PMAA) brushes grafted on porous silicon. Succinimidyl ester (NHS-ester) is generally believed to be the dominant intermediate product, conveniently used to immobilize biomols. contg. free primary amino groups via amide linkage. To the authors' surprise, the IR spectral details revealed that the EDC/NHS activation of PMAA generated anhydride (estd. at around 76% yield and 70% compn.), but not NHS-ester (around 5% yield and 11% compn.) under the well-documented reaction conditions, as the predominant intermediate product. In contrast, EDC/NHS activation of PAA still follows the general rule, i.e., the expected NHS-ester is the dominant intermediate product (around 45% yield and 57% compn.), anhydride the side product (40% yield and 28% compn.), under the optimum reaction conditions. The following amidation on PAA-based NHS-esters with a model amine-contg. compd., L-leucine Me ester, generated approx. 70% amides and 30% carboxylates. In contrast, amidation of PAA- or PMAA-based anhydrides with L-leucine Me ester only produced less than 30% amides but more than 70% carboxylates. The above reaction yields and percentage compns. were estd. by fitting the carbonyl stretching region with 5 possible species, NHS-ester, anhydride, N-acylurea, unreacted acid, unhydrolyzed tert-Bu ester, and using the Beer-Lambert law. The different surface chem. mechanisms will bring significant effects on the performance of surface chem.-derived devices such as biochips, biosensors, and biomaterials.
- 280Srivastava, I.; Xue, R.; Jones, J.; Rhee, H.; Flatt, K.; Gruev, V.; Nie, S. Biomimetic Surface-Enhanced Raman Scattering Nanoparticles with Improved Dispersibility, Signal Brightness, and Tumor Targeting Functions. ACS Nano 2022, 16, 8051– 8063, DOI: 10.1021/acsnano.2c01062280Biomimetic Surface-Enhanced Raman Scattering Nanoparticles with Improved Dispersibility, Signal Brightness, and Tumor Targeting FunctionsSrivastava, Indrajit; Xue, Ruiyang; Jones, Jamie; Rhee, Hyunjoon; Flatt, Kristen; Gruev, Viktor; Nie, ShumingACS Nano (2022), 16 (5), 8051-8063CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)The development of biocompatible and nontoxic surface-enhanced Raman scattering (SERS) nanoparticles is of considerable current interest because of their attractive biomedical applications such as ultrasensitive in vitro diagnostics, in vivo tumor imaging, and spectroscopy-guided cancer surgery. However, current SERS nanoparticles are prepd. and stored in aq. soln., have limited stability and dispersibility, and are not suitable for lyophilization and storage by freeze-drying or other means. Here, we report a simple but robust method to coat colloidal SERS nanoparticles by naturally derived biomimetic red blood cell membranes (RBCM), leading to a dramatic improvement in stability and dispersibility under freeze-thawing, lyophilization, heating, and physiol. conditions. The results demonstrate that the lyophilized SERS nanoparticles in the solid form can be readily dissolved and dispersed in physiol. buffer solns. A surprising finding is that the RBCM-coated SERS particles are considerably brighter (by as much as 5-fold) than PEGylated SERS particles under similar exptl. conditions. This addnl. enhancement is believed to arise from the hydrophobic nature of RBCM's hydrocarbon chains, which is known to reduce electronic dampening and boost electromagnetic field enhancement. A further advantage in using biomimetic membrane coatings is that the bilayer membrane structure allows nonvalent insertion of mol. ligands for tumor targeting. In particular, we show that cyclic-RGD, a tumor-targeting peptide, can be efficiently inserted into the membrane coatings of SERS nanoparticles for targeting the ανβ3 integrin receptors expressed on cancer cells. Thus, biomimetic RBCMs provide major advantages over traditional polyethylene glycols for prepg. SERS nanoparticles with improved dispersibility, higher signal intensity, and more efficient biofunctionalization.
- 281Srivastava, I.; Xue, R.; Huang, H.-K.; Wang, Z.; Jones, J.; Vasquez, I.; Pandit, S.; Lin, L.; Zhao, S.; Flatt, K.; Gruev, V.; Chen, Y.-S.; Nie, S. Biomimetic-Membrane-Protected Plasmonic Nanostructures as Dual-Modality Contrast Agents for Correlated Surface-Enhanced Raman Scattering and Photoacoustic Detection of Hidden Tumor Lesions. ACS Appl. Mater. & Interfaces 2024, 16, 8554– 8569, DOI: 10.1021/acsami.3c18488There is no corresponding record for this reference.
- 282Srivastava, I.; Lew, B.; Wang, Y.; Blair, S.; George, M. B.; Hajek, B. S.; Bangru, S.; Pandit, S.; Wang, Z.; Ludwig, J.; Flatt, K.; Gruebele, M.; Nie, S.; Gruev, V. Cell-Membrane Coated Nanoparticles for Tumor Delineation and Qualitative Estimation of Cancer Biomarkers at Single Wavelength Excitation in Murine and Phantom Models. ACS Nano 2023, 17, 8465– 8482, DOI: 10.1021/acsnano.3c00578There is no corresponding record for this reference.
- 283Gill, N.; Srivastava, I.; Tropp, J. Rational Design of NIR-II Emitting Conjugated Polymer Derived Nanoparticles for Image-Guided Cancer Interventions. Adv. Healthc Mater. 2024, 13, e2401297, DOI: 10.1002/adhm.202401297There is no corresponding record for this reference.
- 284Stetciura, I. Y.; Yashchenok, A.; Masic, A.; Lyubin, E. V.; Inozemtseva, O. A.; Drozdova, M. G.; Markvichova, E. A.; Khlebtsov, B. N.; Fedyanin, A. A.; Sukhorukov, G. B.; Gorin, D. A.; Volodkin, D. Composite SERS-based satellites navigated by optical tweezers for single cell analysis. Analyst 2015, 140, 4981– 4986, DOI: 10.1039/C5AN00392JThere is no corresponding record for this reference.
- 285Messina, E.; Cavallaro, E.; Cacciola, A.; Saija, R.; Borghese, F.; Denti, P.; Fazio, B.; D’Andrea, C.; Gucciardi, P. G.; Iatì, M. A.; Meneghetti, M.; Compagnini, G.; Amendola, V.; Maragò, O. M. Manipulation and Raman Spectroscopy with Optically Trapped Metal Nanoparticles Obtained by Pulsed Laser Ablation in Liquids. J. Phys. Chem. C 2011, 115, 5115– 5122, DOI: 10.1021/jp109405j285Manipulation and Raman Spectroscopy with Optically Trapped Metal Nanoparticles Obtained by Pulsed Laser Ablation in LiquidsMessina, E.; Cavallaro, E.; Cacciola, A.; Saija, R.; Borghese, F.; Denti, P.; Fazio, B.; D'Andrea, C.; Gucciardi, P. G.; Iati, M. A.; Meneghetti, M.; Compagnini, G.; Amendola, V.; Marago, O. M.Journal of Physical Chemistry C (2011), 115 (12), 5115-5122CODEN: JPCCCK; ISSN:1932-7447. (American Chemical Society)Optical trapping of metal nanoparticles and aggregates were studied exptl. and theor. Light forces can be used to trap individual Au nanoaggregates of controlled size and structure obtained by laser ablation synthesis in soln. Due to their surface charge, no agglomeration of isolated nanoparticles was obsd. during trapping expts. and reliable optical force measurements of isolated and aggregated nanoparticles was possible through an anal. of the Brownian motion in the trap. The field-enhancement properties of these nanostructures enables surface-enhanced Raman spectroscopy of mols. adsorbed on aggregates optically trapped in a Raman tweezers setup. The authors finally discuss calcns. of extinction and optical forces based on a full electromagnetic scattering theory for aggregated Au nanostructures where the occurrence of plasmon resonances at longer wavelength play a crucial role in the enhancement of the trapping forces.
- 286Hong, S.; Shim, O.; Kwon, H.; Choi, Y. Autoenhanced Raman Spectroscopy via Plasmonic Trapping for Molecular Sensing. Anal. Chem. 2016, 88, 7633– 7638, DOI: 10.1021/acs.analchem.6b01451286Autoenhanced Raman Spectroscopy via Plasmonic Trapping for Molecular SensingHong, Soonwoo; Shim, On; Kwon, Hyosung; Choi, YeonhoAnalytical Chemistry (Washington, DC, United States) (2016), 88 (15), 7633-7638CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)As a label-free and sensitive biosensor, surface-enhanced Raman spectroscopy (SERS) is a rapidly emerging technique. However, because SERS spectra are obtained in the area of light excitation and the enhancement effect can be varied depending on the position of a substrate, it is important to match the enhanced area with an illuminated spot. Here, in order to overcome such difficulty, we demonstrated a new technique combining SERS with plasmonic trapping. By plasmonic trapping, we can collect gold nanoparticles (GNPs) in the middle of initially fabricated nanobowtie structures where a laser is excited. As a result of trapping GNPs, hot-spots are formed at that area. Because SERS is measured in the area irradiated by a laser, hot-spot can be simultaneously coincided with a detection site for SERS. By using this, we detected Rhodamine 6G to 100 pM. To further verify and improve the reproducibility of our technique, we also calcd. the elec. field distribution, trapping force and trapping potential.
- 287Dai, X.; Fu, W.; Chi, H.; Mesias, V. S. D.; Zhu, H.; Leung, C. W.; Liu, W.; Huang, J. Optical tweezers-controlled hotspot for sensitive and reproducible surface-enhanced Raman spectroscopy characterization of native protein structures. Nat. Commun. 2021, 12, 1292, DOI: 10.1038/s41467-021-21543-3287Optical tweezers-controlled hotspot for sensitive and reproducible surface-enhanced Raman spectroscopy characterization of native protein structuresDai, Xin; Fu, Wenhao; Chi, Huanyu; Mesias, Vince St. Dollente; Zhu, Hongni; Leung, Cheuk Wai; Liu, Wei; Huang, JinqingNature Communications (2021), 12 (1), 1292CODEN: NCAOBW; ISSN:2041-1723. (Nature Research)Surface-enhanced Raman spectroscopy (SERS) has emerged as a powerful tool to detect biomols. in aq. environments. However, it is challenging to identify protein structures at low concns., esp. for the proteins existing in an equil. mixt. of various conformations. Here, we develop an in situ optical tweezers-coupled Raman spectroscopy to visualize and control the hotspot between two Ag nanoparticle-coated silica beads, generating tunable and reproducible SERS enhancements with single-mol. level sensitivity. This dynamic SERS detection window is placed in a microfluidic flow chamber to detect the passing-by proteins, which precisely characterizes the structures of three globular proteins without perturbation to their native states. Moreover, it directly identifies the structural features of the transient species of alpha-synuclein among its predominant monomers at physiol. concn. of 1μM by reducing the ensemble averaging. Hence, this SERS platform holds the promise to resolve the structural details of dynamic, heterogeneous, and complex biol. systems.
- 288Fu, W.; Chi, H.; Dai, X.; Zhu, H.; Mesias, V. S. D.; Liu, W.; Huang, J. Efficient optical plasmonic tweezer-controlled single-molecule SERS characterization of pH-dependent amylin species in aqueous milieus. Nat. Commun. 2023, 14, 6996, DOI: 10.1038/s41467-023-42812-3There is no corresponding record for this reference.
- 289McNay, G.; Docherty, F. T.; Graham, D.; Smith, W. E.; Jordan, P.; Padgett, M.; Leach, J.; Sinclair, G.; Monaghan, P. B.; Cooper, J. M. Visual Observations of SERRS from Single Silver-Coated Silica Microparticles within Optical Tweezers. Angew. Chem., Int. Ed. 2004, 43, 2512– 2514, DOI: 10.1002/anie.200352999There is no corresponding record for this reference.
- 290Bálint, Š.; Kreuzer, M. P.; Rao, S.; Badenes, G.; Miškovský, P.; Petrov, D. Simple Route for Preparing Optically Trappable Probes for Surface-Enhanced Raman Scattering. J. Phys. Chem. C 2009, 113, 17724– 17729, DOI: 10.1021/jp906318n290Simple Route for Preparing Optically Trappable Probes for Surface-Enhanced Raman ScatteringBalint, Stefan; Kreuzer, Mark P.; Rao, Satish; Badenes, Goncal; Miskovsky, Pavol; Petrov, DmitriJournal of Physical Chemistry C (2009), 113 (41), 17724-17729CODEN: JPCCCK; ISSN:1932-7447. (American Chemical Society)Surface-enhanced Raman scattering (SERS) has proven to be a powerful technique for a wide range of topics such as chem. anal., materials research, and biol. imaging. In this work, the authors report in detail on the development and characterization of micrometer-sized dielec. beads with metal colloids attached to their surface. The metalized beads were sufficiently transparent enabling optical trapping while the presence of metal islands provided the SERS. This method is fast and simple and is void of complications when compared to the Tollen's test used in previous publications. This highly efficient probe can be placed and scanned with nanometric accuracy near living cells. The process to create such probes is described including discussion of various parameters that are crit. in achieving the desired results. Addnl., their use is demonstrated by detecting low quantities of a drug in aq. soln. and in a cell membrane.
- 291Svedberg, F.; Li, Z.; Xu, H.; Käll, M. Creating Hot Nanoparticle Pairs for Surface-Enhanced Raman Spectroscopy through Optical Manipulation. Nano Lett. 2006, 6, 2639– 2641, DOI: 10.1021/nl062101m291Creating Hot Nanoparticle Pairs for Surface-Enhanced Raman Spectroscopy through Optical ManipulationSvedberg, Fredrik; Li, Zhipeng; Xu, Hongxing; Kaell, MikaelNano Letters (2006), 6 (12), 2639-2641CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)We use optical tweezers to move single silver nanoparticles into near-field contact with immobilized particles, forming isolated surface-enhanced Raman spectroscopy (SERS) active Ag particle dimers. The surface-averaged SERS intensity increases by a factor ∼20 upon dimerization. Electrodynamics calcns. indicate that the final approach between the particles is due to "optical binding". The described methodol. may facilitate controlled single mol. SERS anal.
- 292Tong, L.; Righini, M.; Gonzalez, M. U.; Quidant, R.; Käll, M. Optical aggregation of metal nanoparticles in a microfluidic channel for surface-enhanced Raman scattering analysis. Lab Chip 2009, 9, 193– 195, DOI: 10.1039/B813204F292Optical aggregation of metal nanoparticles in a microfluidic channel for surface-enhanced Raman scattering analysisTong, Lianming; Righini, Maurizio; Gonzalez, Maria Ujue; Quidant, Romain; Kaell, MikaelLab on a Chip (2009), 9 (2), 193-195CODEN: LCAHAM; ISSN:1473-0197. (Royal Society of Chemistry)Aggregated metal nanoparticles exhibit enhanced localized electromagnetic fields that enable highly sensitive vibrational spectroscopy anal. based on surface-enhanced Raman scattering (SERS). We demonstrate SERS detection of org. analytes adsorbed to optically aggregated silver nanoparticles in a microfluidic device. The combination of optical tweezers and microfluidics technologies paves the way for novel lab-on-a-chip based plasmonic chemo/bio sensors and overcomes two important drawbacks of std. SERS sensing schemes; i.e. the renewal of nanofabricated metallic substrates and the difficulty of avoiding uncontrolled aggregation in metal colloids.
- 293Fazio, B.; D’Andrea, C.; Foti, A.; Messina, E.; Irrera, A.; Donato, M. G.; Villari, V.; Micali, N.; Maragò, O. M.; Gucciardi, P. G. SERS detection of Biomolecules at Physiological pH via aggregation of Gold Nanorods mediated by Optical Forces and Plasmonic Heating. Sci. Rep. 2016, 6, 26952, DOI: 10.1038/srep26952293SERS detection of Biomolecules at Physiological pH via aggregation of Gold Nanorods mediated by Optical Forces and Plasmonic HeatingFazio, Barbara; D'Andrea, Cristiano; Foti, Antonino; Messina, Elena; Irrera, Alessia; Donato, Maria Grazia; Villari, Valentina; Micali, Norberto; Marago, Onofrio M.; Gucciardi, Pietro G.Scientific Reports (2016), 6 (), 26952CODEN: SRCEC3; ISSN:2045-2322. (Nature Publishing Group)Strategies for in-liq. mol. detection via Surface Enhanced Raman Scattering (SERS) are currently based on chem.-driven aggregation or optical trapping of metal nanoparticles in presence of the target mols. Such strategies allow the formation of SERS-active clusters that efficiently embed the mol. at the "hot spots" of the nanoparticles and enhance its Raman scattering by orders of magnitude. Here we report on a novel scheme that exploits the radiation pressure to locally push gold nanorods and induce their aggregation in buffered solns. of biomols., achieving biomol. SERS detection at almost neutral pH. The sensor is applied to detect non-resonant amino acids and proteins, namely Phenylalanine (Phe), Bovine Serum Albumin (BSA) and Lysozyme (Lys), reaching detection limits in the μg/mL range. Being a chem. free and contactless technique, our methodol. is easy to implement, fast to operate, needs small sample vols. and has potential for integration in microfluidic circuits for biomarkers detection.
- 294Lu, W.; Chen, X.; Wang, L.; Li, H.; Fu, Y. V. Combination of an Artificial Intelligence Approach and Laser Tweezers Raman Spectroscopy for Microbial Identification. Anal. Chem. 2020, 92, 6288– 6296, DOI: 10.1021/acs.analchem.9b04946294Combination of an Artificial Intelligence Approach and Laser Tweezers Raman Spectroscopy for Microbial IdentificationLu, Weilai; Chen, Xiuqiang; Wang, Lu; Li, Hanfei; Fu, Yu VincentAnalytical Chemistry (Washington, DC, United States) (2020), 92 (9), 6288-6296CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Raman spectroscopy is a nondestructive, label-free, highly specific approach that provides the chem. information on materials. Thus, it is suitable to be used as an effective anal. tool to characterize biol. samples. Here we introduce a novel method that uses artificial intelligence to analyze biol. Raman spectra and identify the microbes at a single-cell level. The combination of a framework of convolutional neural network (ConvNet) and Raman spectroscopy allows the extn. of the Raman spectral features of a single microbial cell and then categorizes cells according to their spectral features. As the proof of concept, we measured Raman spectra of 14 microbial species at a single-cell level and constructed an optimal ConvNet model using the Raman data. The av. accuracy of classification by ConvNet is 95.64 ± 5.46%. Meanwhile, we introduced an occlusion-based Raman spectra feature extn. to visualize the wts. of Raman features for distinguishing different species.
- 295Shang, L.; Liang, P.; Xu, L.; Xue, Y.; Liu, K.; Wang, Y.; Bao, X.; Chen, F.; Peng, H.; Wang, Y.; Ju, J.; Li, B. Stable SERS Detection of Lactobacillus fermentum Using Optical Tweezers in a Microfluidic Environment. Anal. Chem. 2024, 96, 248– 255, DOI: 10.1021/acs.analchem.3c03852There is no corresponding record for this reference.
- 296Kitahama, Y.; Funaoka, M.; Ozaki, Y. Plasmon-Enhanced Optical Tweezers for Single Molecules on and near a Colloidal Silver Nanoaggregate. J. Phys. Chem. C 2019, 123, 18001– 18006, DOI: 10.1021/acs.jpcc.9b05626296Plasmon-Enhanced Optical Tweezers for Single Molecules on and near a Colloidal Silver NanoaggregateKitahama, Yasutaka; Funaoka, Misato; Ozaki, YukihiroJournal of Physical Chemistry C (2019), 123 (29), 18001-18006CODEN: JPCCCK; ISSN:1932-7447. (American Chemical Society)At the junction of an Ag nanoaggregate, single mols. can emit surface-enhanced Raman scattering and fluorescence (SERS and SEF) and can be optically trapped by an enhanced electromagnetic field via plasmon resonance. Blinking SERS and SEF from a single mol. on the same nanoaggregate were obsd. simultaneously in a bicolor movie. By super-resoln. imaging, the positions of the SERS- and SEF-active mols. were detected beyond the diffraction limit. The spatial fluctuation of the mol. on the nanoaggregate was suppressed as the excitation laser intensity increased. The reason is that the single mol. was optically trapped at the junction via plasmon resonance because the mislocalization effect and the signal intensity do not influence a change in the spatial fluctuation in the super-resoln. imaging. The spatial fluctuation of the SEF-active mol. near the Ag surface was larger than that of the SERS-active mol. adsorbed on the surface. The power spectral d. revealed that the plasmon-enhanced optically trapped mol. by excitation at high laser intensity moved randomly rather than harmonically.
- 297Oyamada, N.; Minamimoto, H.; Murakoshi, K. Room-Temperature Molecular Manipulation via Plasmonic Trapping at Electrified Interfaces. J. Am. Chem. Soc. 2022, 144, 2755– 2764, DOI: 10.1021/jacs.1c12213297Room-Temperature Molecular Manipulation via Plasmonic Trapping at Electrified InterfacesOyamada, Nobuaki; Minamimoto, Hiro; Murakoshi, KeiJournal of the American Chemical Society (2022), 144 (6), 2755-2764CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)For the motion control of individual mols. at room temp., optical tweezers could be one of the best approaches to realize desirable selectivity with high resoln. in time and space. Because of phys. limitations due to the thermal fluctuation, optical manipulation of small mols. at room temp. is still a challenging subject. The difficulty of the manipulation also emerged from the variation of mol. polarizability depending on the choice of mols. as well as the mol. orientation to the optical field. In this article, we have demonstrated plasmonic optical trapping of small size mols. with less than 1 nm at the gap of a single metal nanodimer immersed in an electrolyte soln. In situ electrochem. surface-enhanced Raman scattering measurements prove that a plasmonic structure under electrochem. potential control realizes not only the selective mol. condensation but also the formation of unique mixed mol. phases which is distinct from those under a thermodn. equil. Through detailed analyses of optical trapping behavior, we established the methodol. of plasmonic optical trapping to create the novel adsorption isotherm under applying an optical force at electrified interfaces.
- 298Yang, W.; van Dijk, M.; Primavera, C.; Dekker, C. FIB-milled plasmonic nanoapertures allow for long trapping times of individual proteins. iScience 2021, 24, 103237, DOI: 10.1016/j.isci.2021.103237298FIB-milled plasmonic nanoapertures allow for long trapping times of individual proteinsYang, Wayne; van Dijk, Madeleine; Primavera, Christian; Dekker, CeesiScience (2021), 24 (11), 103237CODEN: ISCICE; ISSN:2589-0042. (Elsevier B.V.)We have developed a fabrication methodol. for label-free optical trapping of individual nanobeads and proteins in inverted-bowtie-shaped plasmonic gold nanopores. Arrays of these nanoapertures can be reliably produced using focused ion beam (FIB) milling with gap sizes of 10-20 nm, single-nanometer variation, and with a remarkable stability that allows for repeated use. We employ an optical readout where the presence of the protein entering the trap is marked by an increase in the transmission of light through the nanoaperture from the shift of the plasmonic resonance. In addn., the optical trapping force of the plasmonic nanopores allows 20-nm polystyrene beads and proteins, such as beta-amylase and Heat Shock Protein (HSP90), to be trapped for very long times (approx. minutes). On demand, we can release the trapped mol. for another protein to be interrogated. Our work opens up new routes to acquire information on the conformation and dynamics of individual proteins.
- 299Hernández-Sarria, J. J.; Oliveira, O. N.; Mejía-Salazar, J. R. Toward Lossless Infrared Optical Trapping of Small Nanoparticles Using Nonradiative Anapole Modes. Phys. Rev. Lett. 2021, 127, 186803, DOI: 10.1103/PhysRevLett.127.186803299Toward Lossless Infrared Optical Trapping of Small Nanoparticles Using Nonradiative Anapole ModesHernandez-Sarria, J. J.; Oliveira, Jr., Osvaldo N.; Mejia-Salazar, J. R.Physical Review Letters (2021), 127 (18), 186803CODEN: PRLTAO; ISSN:1079-7114. (American Physical Society)A challenge in plasmonic trapping of small nanoparticles is the heating due to the Joule effect of metallic components. This heating can be avoided with electromagnetic field confinement in high-refractive-index materials, but nanoparticle trapping is difficult because the electromagnetic fields are mostly confined inside the dielec. nanostructures. Herein, we present the design of an all-dielec. platform to capture small dielec. nanoparticles without heating the nanostructure. It consists of a Si nanodisk engineered to exhibit the second-order anapole mode at the IR regime (λ=980 nm), where Si has negligible losses, with a slot at the center. A strong electromagnetic hot spot is created, thus allowing us to capture nanoparticles as small as 20 nm. The numerical calcns. indicate that optical trapping in these all-dielec. nanostructures occurs without heating only in the IR, since for visible wavelengths the heating levels are similar to those in plasmonic nanostructures.
- 300Hernandez-Sarria, J. J.; Oliveira, O. N., Jr; Mejía-Salazar, J. R. Numerical simulations of double-well optical potentials in all-dielectric nanostructures for manipulation of small nanoparticles in aqueous media. ACS Applied Nano Materials 2023, 6, 1405– 1412, DOI: 10.1021/acsanm.2c05047There is no corresponding record for this reference.
- 301Hong, I.; Hong, C.; Tutanov, O. S.; Massick, C.; Castleberry, M.; Zhang, Q.; Jeppesen, D. K.; Higginbotham, J. N.; Franklin, J. L.; Vickers, K.; Coffey, R. J.; Ndukaife, J. C. Anapole-Assisted Low-Power Optical Trapping of Nanoscale Extracellular Vesicles and Particles. Nano Lett. 2023, 23, 7500– 7507, DOI: 10.1021/acs.nanolett.3c02014301Anapole-Assisted Low-Power Optical Trapping of Nanoscale Extracellular Vesicles and ParticlesHong, Ikjun; Hong, Chuchuan; Tutanov, Oleg S.; Massick, Clark; Castleberry, Mark; Zhang, Qin; Jeppesen, Dennis K.; Higginbotham, James N.; Franklin, Jeffrey L.; Vickers, Kasey; Coffey, Robert J.; Ndukaife, Justus C.Nano Letters (2023), 23 (16), 7500-7507CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)This study addresses the challenge of trapping nanoscale biol. particles using optical tweezers without the photothermal heating effect and the limitation presented by the diffraction limit. Optical tweezers are effective for trapping microscopic biol. objects but not for nanoscale specimens due to the diffraction limit. To overcome this, we present an approach that uses optical anapole states in all-dielec. nanoantenna systems on distributed Bragg reflector substrates to generate strong optical gradient force and potential on nanoscale biol. objects with negligible temp. rise below 1 K. The anapole antenna condenses the accessible electromagnetic energy to scales as small as 30 nm. Using this approach, we successfully trapped nanosized extracellular vesicles and supermeres (approx. 25 nm in size) using low laser power of only 10.8 mW. This nanoscale optical trapping platform has great potential for single mol. anal. while precluding photothermal degrdn.
- 302Conteduca, D.; Brunetti, G.; Barth, I.; Quinn, S. D.; Ciminelli, C.; Krauss, T. F. Multiplexed Near-Field Optical Trapping Exploiting Anapole States. ACS Nano 2023, 17, 16695– 16702, DOI: 10.1021/acsnano.3c03100There is no corresponding record for this reference.
- 303Zhang, R.; Zhang, Y.; Dong, Z. C.; Jiang, S.; Zhang, C.; Chen, L. G.; Zhang, L.; Liao, Y.; Aizpurua, J.; Luo, Y.; Yang, J. L.; Hou, J. G. Chemical mapping of a single molecule by plasmon-enhanced Raman scattering. Nature 2013, 498, 82– 86, DOI: 10.1038/nature12151303Chemical mapping of a single molecule by plasmon-enhanced Raman scatteringZhang, R.; Zhang, Y.; Dong, Z. C.; Jiang, S.; Zhang, C.; Chen, L. G.; Zhang, L.; Liao, Y.; Aizpurua, J.; Luo, Y.; Yang, J. L.; Hou, J. G.Nature (London, United Kingdom) (2013), 498 (7452), 82-86CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)Visualizing individual mols. with chem. recognition is a longstanding target in catalysis, mol. nanotechnol. and biotechnol. Mol. vibrations provide a valuable fingerprint' for such identification. Vibrational spectroscopy based on tip-enhanced Raman scattering allows us to access the spectral signals of mol. species very efficiently via the strong localized plasmonic fields produced at the tip apex. However, the best spatial resoln. of the tip-enhanced Raman scattering imaging is still limited to 3-15 nm, which is not adequate for resolving a single mol. chem. Here we demonstrate Raman spectral imaging with spatial resoln. below one nanometer, resolving the inner structure and surface configuration of a single mol. This is achieved by spectrally matching the resonance of the nanocavity plasmon to the mol. vibronic transitions, particularly the downward transition responsible for the emission of Raman photons. This matching is made possible by the extremely precise tuning capability provided by scanning tunneling microscopy. Exptl. evidence suggests that the highly confined and broadband nature of the nanocavity plasmon field in the tunnelling gap is essential for ultrahigh-resoln. imaging through the generation of an efficient double-resonance enhancement for both Raman excitation and Raman emission. Our technique not only allows for chem. imaging at the single-mol. level, but also offers a new way to study the optical processes and photochem. of a single mol.
- 304Jaculbia, R. B.; Imada, H.; Miwa, K.; Iwasa, T.; Takenaka, M.; Yang, B.; Kazuma, E.; Hayazawa, N.; Taketsugu, T.; Kim, Y. Single-molecule resonance Raman effect in a plasmonic nanocavity. Nat. Nanotechnol. 2020, 15, 105– 110, DOI: 10.1038/s41565-019-0614-8304Single-molecule resonance Raman effect in a plasmonic nanocavityJaculbia, Rafael B.; Imada, Hiroshi; Miwa, Kuniyuki; Iwasa, Takeshi; Takenaka, Masato; Yang, Bo; Kazuma, Emiko; Hayazawa, Norihiko; Taketsugu, Tetsuya; Kim, YousooNature Nanotechnology (2020), 15 (2), 105-110CODEN: NNAABX; ISSN:1748-3387. (Nature Research)Tip-enhanced Raman spectroscopy (TERS) is a versatile tool for chem. anal. at the nanoscale. In earlier TERS expts., Raman modes with components parallel to the tip were studied based on the strong elec. field enhancement along the tip. Perpendicular modes were usually neglected. Here, we investigate an isolated copper naphthalocyanine mol. adsorbed on a triple-layer NaCl on Ag(111) using scanning tunnelling microscope TERS imaging. For flat-lying mols. on NaCl, the Raman images present different patterns depending on the symmetry of the vibrational mode. Our results reveal that components of the elec. field perpendicular to the tip should be considered aside from the parallel components. Moreover, under resonance excitation conditions, the perpendicular components can play a substantial role in the enhancement. This single-mol. study in a well-defined environment provides insights into the Raman process at the plasmonic nanocavity, which may be useful in the nanoscale metrol. of various mol. systems.
- 305Benz, F.; Tserkezis, C.; Herrmann, L. O.; de Nijs, B.; Sanders, A.; Sigle, D. O.; Pukenas, L.; Evans, S. D.; Aizpurua, J.; Baumberg, J. J. Nanooptics of Molecular-Shunted Plasmonic Nanojunctions. Nano Lett. 2015, 15, 669– 674, DOI: 10.1021/nl5041786305Nanooptics of Molecular-Shunted Plasmonic NanojunctionsBenz, Felix; Tserkezis, Christos; Herrmann, Lars O.; de Nijs, Bart; Sanders, Alan; Sigle, Daniel O.; Pukenas, Laurynas; Evans, Stephen D.; Aizpurua, Javier; Baumberg, Jeremy J.Nano Letters (2015), 15 (1), 669-674CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)Gold nanoparticles are sepd. above a planar gold film by 1.1 nm thick self-assembled mol. monolayers of different conductivities. Incremental replacement of the nonconductive mols. with a chem. equiv. conductive version differing by only one atom produces a strong 50 nm blue-shift of the coupled plasmon. With modeling this gives a conductance of 0.17G0 per biphenyl-4,4'-dithiol mol. and a total conductance across the plasmonic junction of 30G0. Our approach provides a reliable tool quantifying the no. of mols. in each plasmonic hotspot, here <200.
- 306Li, L.; Hutter, T.; Steiner, U.; Mahajan, S. Single molecule SERS and detection of biomolecules with a single gold nanoparticle on a mirror junction. Analyst 2013, 138, 4574– 4578, DOI: 10.1039/c3an00447c306Single molecule SERS and detection of biomolecules with a single gold nanoparticle on a mirror junctionLi, Li; Hutter, Tanya; Steiner, Ullrich; Mahajan, SumeetAnalyst (Cambridge, United Kingdom) (2013), 138 (16), 4574-4578CODEN: ANALAO; ISSN:0003-2654. (Royal Society of Chemistry)Using the bianalyte method we unambiguously demonstrate that a single gold nanosphere on a metal film junction, in the so-called nanoparticle on a mirror configuration, is capable of single mol. detection with surface-enhanced Raman spectroscopy (SERS). Also this configuration serves as a convenient and highly sensitive SERS sensor for detection of biomols. Such simple nano-junction based systems are ideal for chem. and biomedical anal.
- 307Zhang, Y.; Zhen, Y.-R.; Neumann, O.; Day, J. K.; Nordlander, P.; Halas, N. J. Coherent anti-Stokes Raman scattering with single-molecule sensitivity using a plasmonic Fano resonance. Nat. Commun. 2014, 5, 4424, DOI: 10.1038/ncomms5424307Coherent anti-Stokes Raman scattering with single-molecule sensitivity using a plasmonic Fano resonanceZhang, Yu; Zhen, Yu-Rong; Neumann, Oara; Day, Jared K.; Nordlander, Peter; Halas, Naomi J.Nature Communications (2014), 5 (), 4424CODEN: NCAOBW; ISSN:2041-1723. (Nature Publishing Group)Plasmonic nanostructures are of particular interest as substrates for the spectroscopic detection and identification of individual mols. Single-mol. sensitivity Raman detection has been achieved by combining resonant mol. excitation with large electromagnetic field enhancements experienced by a mol. assocd. with an interparticle junction. Detection of mols. with extremely small Raman cross-sections (∼10-30 cm2 sr-1), however, has remained elusive. Here we show that coherent anti-Stokes Raman spectroscopy (CARS), a nonlinear spectroscopy of great utility and potential for mol. sensing, can be used to obtain single-mol. detection sensitivity, by exploiting the unique light harvesting properties of plasmonic Fano resonances. The CARS signal is enhanced by ∼11 orders of magnitude relative to spontaneous Raman scattering, enabling the detection of single mols., which is verified using a statistically rigorous bi-analyte method. This approach combines unprecedented single-mol. spectral sensitivity with plasmonic substrates that can be fabricated using top-down lithog. strategies.
- 308Lim, D.-K.; Jeon, K.-S.; Kim, H. M.; Nam, J.-M.; Suh, Y. D. Nanogap-engineerable Raman-active nanodumbbells for single-molecule detection. Nat. Mater. 2010, 9, 60– 67, DOI: 10.1038/nmat2596308Nanogap-engineerable Raman-active nanodumbbells for single-molecule detectionLim, Dong-Kwon; Jeon, Ki-Seok; Kim, Hyung Min; Nam, Jwa-Min; Suh, Yung DougNature Materials (2010), 9 (1), 60-67CODEN: NMAACR; ISSN:1476-1122. (Nature Publishing Group)Surface-enhanced Raman scattering (SERS)-based signal amplification and detection methods using plasmonic nanostructures have been widely investigated for imaging and sensing applications. However, SERS-based mol. detection strategies have not been practically useful because there is no straightforward method to synthesize and characterize highly sensitive SERS-active nanostructures with sufficiently high yield and efficiency, which results in an extremely low cross-section area in Raman sensing. Here, the authors report a high-yield synthetic method for SERS-active gold-silver core-shell nanodumbbells, where the gap between two nanoparticles and the Raman-dye position and environment can be engineered on the nanoscale. Atomic-force-microscope-correlated nano-Raman measurements of individual dumbbell structures demonstrate that Raman signals can be repeatedly detected from single-DNA-tethered nanodumbbells. These programmed nanostructure fabrication and single-DNA detection strategies open avenues for the high-yield synthesis of optically active smart nanoparticles and structurally reproducible nanostructure-based single-mol. detection and bioassays.
- 309Liu, S.-C.; Xie, B.-K.; Zhong, C.-B.; Wang, J.; Ying, Y.-L.; Long, Y.-T. An advanced optical–electrochemical nanopore measurement system for single-molecule analysis. Rev. Sci. Instrum. 2021, 92, 121301, DOI: 10.1063/5.0067185309An advanced optical-electrochemical nanopore measurement system for single-molecule analysisLiu, Shao-Chuang; Xie, Bao-Kang; Zhong, Cheng-Bing; Wang, Jia; Ying, Yi-Lun; Long, Yi-TaoReview of Scientific Instruments (2021), 92 (12), 121301CODEN: RSINAK; ISSN:0034-6748. (American Institute of Physics)Nanopore measurement has advanced in single-mol. anal. by providing a transient time and confined space window that only allows one interested mol. to exist. By optimization and integration of the elec. and optical anal. strategies in this transient window, the acquisition of comprehensive information could be achieved to resolve the intrinsic properties and heterogeneity of a single mol. In this work, we present a roadmap to build a unified optical and electrochem. synchronous measurement platform for the research of a single mol. We design a low-cost ultralow-current amplifier with low noise and high-bandwidth to measure the ionic current events as a single mol. translocates through a nanopore and combine a multi-functional optical system to implement the acquisition of the fluorescence, scattering spectrum, and photocurrent intensity of single mol. events in a nanopore confined space. Our system is a unified and unique platform for the protein nanopore, the solid-state nanopore, and the glass capillary nanopore, which has advantages in the comprehensive research of nanopore single-mol. techniques. (c) 2021 American Institute of Physics.
- 310Belkin, M.; Chao, S.-H.; Jonsson, M. P.; Dekker, C.; Aksimentiev, A. Plasmonic Nanopores for Trapping, Controlling Displacement, and Sequencing of DNA. ACS Nano 2015, 9, 10598– 10611, DOI: 10.1021/acsnano.5b04173310Plasmonic nanopores for trapping, controlling displacement, and sequencing of DNABelkin, Maxim; Chao, Shu-Han; Jonsson, Magnus P.; Dekker, Cees; Aksimentiev, AlekseiACS Nano (2015), 9 (11), 10598-10611CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)With the aim of developing a DNA sequencing methodol., we theor. examine the feasibility of using nanoplasmonics to control the translocation of a DNA mol. through a solid-state nanopore and to read off sequence information using surface-enhanced Raman spectroscopy. Using mol. dynamics simulations, we show that high-intensity optical hot spots produced by a metallic nanostructure can arrest DNA translocation through a solid-state nanopore, thus providing a phys. knob for controlling the DNA speed. Switching the plasmonic field on and off can displace the DNA mol. in discrete steps, sequentially exposing neighboring fragments of a DNA mol. to the pore as well as to the plasmonic hot spot. Surface-enhanced Raman scattering from the exposed DNA fragments contains information about their nucleotide compn., possibly allowing the identification of the nucleotide sequence of a DNA mol. transported through the hot spot. The principles of plasmonic nanopore sequencing can be extended to detection of DNA modifications and RNA characterization.
- 311Shi, X.; Verschueren, D.; Pud, S.; Dekker, C. Integrating Sub-3 nm Plasmonic Gaps into Solid-State Nanopores. Small 2018, 14, 1703307, DOI: 10.1002/smll.201703307There is no corresponding record for this reference.
- 312Shi, X.; Verschueren, D. V.; Dekker, C. Active Delivery of Single DNA Molecules into a Plasmonic Nanopore for Label-Free Optical Sensing. Nano Lett. 2018, 18, 8003– 8010, DOI: 10.1021/acs.nanolett.8b04146312Active Delivery of Single DNA Molecules into a Plasmonic Nanopore for Label-Free Optical SensingShi, Xin; Verschueren, Daniel V.; Dekker, CeesNano Letters (2018), 18 (12), 8003-8010CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)Plasmon resonance biosensors provide ultimate sensitivity at the single-mol. level. This sensitivity is, however, assocd. with a nanometer-sized confined hotspot, and mol. transport toward the sensor relies on inefficient diffusion. Here, the authors combine a plasmonic nanoantenna with a solid-state nanopore and demonstrate that single DNA mols. can be efficiently delivered to the plasmonic hotspots and detected in a label-free manner at submillisecond acquisition rates by monitoring the backscattered light intensity from the plasmonic nanoantennas. The method realizes a better than 200 μs temporal resoln. together with a down to subsecond waiting time, which is orders of magnitude better than traditional single-mol. plasmonic resonance sensing methods. Furthermore, the elec. field applied to the nanopore can actively drive biomols. away from the hotspot, preventing mols. to permanently bind to the gold sensor surface and allowing efficient reuse of the sensor. The plasmonic nanopore sensor thus significantly outperforms conventional plasmon resonance sensors and provides great opportunities for high-throughput optical single-mol.-sensing assays.
- 313Li, W.; Zhou, J.; Maccaferri, N.; Krahne, R.; Wang, K.; Garoli, D. Enhanced Optical Spectroscopy for Multiplexed DNA and Protein-Sequencing with Plasmonic Nanopores: Challenges and Prospects. Anal. Chem. 2022, 94, 503– 514, DOI: 10.1021/acs.analchem.1c04459313Enhanced Optical Spectroscopy for Multiplexed DNA and Protein-Sequencing with Plasmonic Nanopores: Challenges and ProspectsLi, Wang; Zhou, Juan; Maccaferri, Nicolo; Krahne, Roman; Wang, Kang; Garoli, DenisAnalytical Chemistry (Washington, DC, United States) (2022), 94 (2), 503-514CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)A review. Nanopore sequencing is currently a widely used technol. for single-mol. DNA detection and anal. Although the error rate is still too high to enable diagnostic applications, biol. nanopores have demonstrated to be able to read the sequence of single DNA mol., and massive efforts are now ongoing to exploit the same technol. for decoding single proteins. In this framework, solid-state nanopore-based sensors have emerged as alternative platforms for single-mol. sequencing. They did not demonstrate yet to enable reliable DNA sequencing, but they can be easily engineered to include addnl. functionalities, such as mech. robustness and versatile chem. functionalization. Among the different classes of solid-state nanopores, plasmonic nanopores have rapidly attracted the interest within the nanopore community, since they allow to engineer the electromagnetic field, which can be exploited as an advanced tool for enhanced optical spectroscopy and tweezing, as well as local control over temp. More importantly, plasmonic nanopores are the most versatile platform to realize electro-optical single-mol. detection and to explore integrated sequencing methods. In particular, the use of optical read-out in single-mol. sequencing is a key aspect to tackle the challenging goal of protein sequencing, a goal that is more than challenging to achieve using elec. read-out approaches. This crit. Review offers a comprehensive understanding of the most recent state-of-the-art plasmonic nanopores for single-mol. detection and biomol. sequencing applications, and discusses the latest advances and future perspectives on plasmonic nanopore-based technologies, focusing the discussion on the crit. aspects to be overcome to enable multiplexing anal. of DNA and protein with single-mol. sensitivity.
- 314Hubarevich, A.; Huang, J.-A.; Giovannini, G.; Schirato, A.; Zhao, Y.; Maccaferri, N.; De Angelis, F.; Alabastri, A.; Garoli, D. λ-DNA through Porous Materials─Surface-Enhanced Raman Scattering in a Simple Plasmonic Nanopore. J. Phys. Chem. C 2020, 124, 22663– 22670, DOI: 10.1021/acs.jpcc.0c06165314λ-DNA through Porous Materials-Surface-Enhanced Raman Scattering in a Simple Plasmonic NanoporeHubarevich, Aliaksandr; Huang, Jian-An; Giovannini, Giorgia; Schirato, Andrea; Zhao, Yingqi; Maccaferri, Nicolo; De Angelis, Francesco; Alabastri, Alessandro; Garoli, DenisJournal of Physical Chemistry C (2020), 124 (41), 22663-22670CODEN: JPCCCK; ISSN:1932-7447. (American Chemical Society)Engineered electromagnetic fields in plasmonic nanopores enable enhanced optical detection for single-mol. sensing and sequencing. Here, a plasmonic nanopore prepd. in a thick nanoporous film was used to study, by surface-enhanced Raman spectroscopy, the interaction between the metallic surface of the pore and a long-chain double-strand DNA mol. free to diffuse through the pore. How the matrix of the porous material can interact with the mol. thanks to: (1) transient aspecific interactions between the porous surface and DNA; (2) diffusion; and (3) thermal and optical forces exerted by the localized field in a metallic nanostructure on the DNA mol are discussed. An interaction time up to tens of milliseconds enables the authors to collect high signal-to-noise Raman signatures, allowing an easy label-free reading of information from the DNA mol. Moreover, to increase the rate of detection, the authors tested a polymeric porous hydrogel placed beneath the solid-state membrane. The hydrogel enables a slowdown of the mol. diffusion time, thus increasing the no. of detected interaction events by a factor 20. The anal. of the obsd. Raman peaks and their relative intensities, combined with theor. simulations, allows the authors to get further information on the process of translocation and the folding state and orientation of the translocating mol. The authors' results demonstrate temporary adsorption of the DNA mol. on the porous material during the translocation due to the diffusion force. Finally, the authors provide a qual. evaluation of the nucleotides' contents in the different groups of collected signal. The proposed approach can find interesting applications not only in DNA sensing and sequencing but also on generic nanopore spectroscopy.
- 315Assad, O. N.; Gilboa, T.; Spitzberg, J.; Juhasz, M.; Weinhold, E.; Meller, A. Light-Enhancing Plasmonic-Nanopore Biosensor for Superior Single-Molecule Detection. Adv. Mater. 2017, 29, 1605442, DOI: 10.1002/adma.201605442There is no corresponding record for this reference.
- 316Zhao, Y.; Hubarevich, A.; De Fazio, A. F.; Iarossi, M.; Huang, J.-A.; De Angelis, F. Plasmonic Bowl-Shaped Nanopore for Raman Detection of Single DNA Molecules in Flow-Through. Nano Lett. 2023, 23, 4830– 4836, DOI: 10.1021/acs.nanolett.3c00340316Plasmonic Bowl-Shaped Nanopore for Raman Detection of Single DNA Molecules in Flow-ThroughZhao, Yingqi; Hubarevich, Aliaksandr; De Fazio, Angela Federica; Iarossi, Marzia; Huang, Jian-An; De Angelis, FrancescoNano Letters (2023), 23 (11), 4830-4836CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)A review. Plasmonic nanopores combined with Raman spectroscopy are emerging as platforms for single-mol. detection and sequencing in label-free mode. Recently, the ability of identifying single DNA bases or amino acids has been demonstrated for mols. adsorbed on plasmonic particles and then delivered into the plasmonic pores. Here, we report on bowl-shaped plasmonic gold nanopores capable of direct Raman detection of single λ-DNA mols. in a flow-through scheme. The bowl shape enables the incident laser to be focused into the nanopore to generate a single intense hot spot with no cut off in pore size. Therefore, we achieved ultrasmall focusing of NIR light in a spot of 3 nm. This enabled us to detect 7 consecutive bases along the DNA chain in flow-through conditions. Furthermore, we found a novel electrofluidic mechanism to manipulate the mol. trajectory within the pore vol. so that the mol. is pushed toward the hot spot, thus improving the detection efficiency.
- 317Shen, Q.; Zhou, P.-L.; Huang, B.-T.; Zhou, J.; Liu, H.-L.; Ahmed, S. A.; Ding, X.-L.; Li, J.; Zhai, Y.-M.; Wang, K. Mass transport through a sub-10 nm single gold nanopore: SERS and ionic current measurement. J. Electroanal. Chem. 2021, 894, 115373, DOI: 10.1016/j.jelechem.2021.115373317Mass transport through a sub-10 nm single gold nanopore: SERS and ionic current measurementShen, Qi; Zhou, Pan-Ling; Huang, Bin-Tong; Zhou, Juan; Liu, Hai-Ling; Ahmed, Saud Asif; Ding, Xin-Lei; Li, Jian; Zhai, Yue-Ming; Wang, KangJournal of Electroanalytical Chemistry (2021), 894 (), 115373CODEN: JECHES; ISSN:1873-2569. (Elsevier B.V.)Au nanopore is promising to be used in single mol. sequencing by measuring surface enhanced Raman scattering (SERS) spectrum. To achieve this goal, fabrication of small and size-controllable single Au nanopore is in urgent need. The authors synthesized Au nanoplates with a sub-10 nm single nanopore at the center, which was then successfully attached at the tip of a glass nanopipette using sulfhydryl silane. The transport of ∼1.4 × 103 rhodamine 6G mols. was detected using SERS. The current blockage caused by single lambda DNA passing through the nanopore was also obsd. The translocation time of lambda DNA through the Au nanopore was much longer than that of lambda DNA through the bare glass nanopipette, revealing the strong DNA-Au nanopore interaction affected the transport behavior of lambda DNA. The obsd. result further shows that the time resoln. of SERS ( approx. ms) may match the transport time of DNA through plasmonic nanopore. The sub-10 nm Au nanopore is possible to be used in single mol. transport detection with the improvement of the nanopore attachment.
- 318Cao, J.; Liu, H.-L.; Yang, J.-M.; Li, Z.-Q.; Yang, D.-R.; Ji, L.-N.; Wang, K.; Xia, X.-H. SERS Detection of Nucleobases in Single Silver Plasmonic Nanopores. ACS Sens. 2020, 5, 2198– 2204, DOI: 10.1021/acssensors.0c00844318SERS Detection of Nucleobases in Single Silver Plasmonic NanoporesCao, Jiao; Liu, Hai-Ling; Yang, Jin-Mei; Li, Zhong-Qiu; Yang, Dong-Rui; Ji, Li-Na; Wang, Kang; Xia, Xing-HuaACS Sensors (2020), 5 (7), 2198-2204CODEN: ASCEFJ; ISSN:2379-3694. (American Chemical Society)Conventional ion current-based nanopore techniques that identify single mols. are hampered by limitations of providing only the ionic current information. Here, the authors introduce a silver nanotriangle-based nanopore (diam. < 50 nm) system for detecting mol. translocation using surface-enhanced Raman scattering. Rhodamine 6G was used as a model mol. to study the effect of an elec. field (-1 V) on the mass transport. The four DNA bases also show significantly different SERS signals when they are transported into the plasmonic nanopore. The observations suggest that in the elec. field, analyte mols. are driven into the nanopipette through the hot spot of the silver nanopore. The plasmonic nanopore shows great potential as a highly sensitive SERS platform for detecting mol. transport and paves the way for single mol. probing.
- 319Zhou, J.; Lan, Q.; Li, W.; Ji, L.-N.; Wang, K.; Xia, X.-H. Single Molecule Protein Segments Sequencing by a Plasmonic Nanopore. Nano Lett. 2023, 23, 2800– 2807, DOI: 10.1021/acs.nanolett.3c00086There is no corresponding record for this reference.
- 320Shendure, J.; Balasubramanian, S.; Church, G. M.; Gilbert, W.; Rogers, J.; Schloss, J. A.; Waterston, R. H. DNA sequencing at 40: past, present and future. Nature 2017, 550, 345– 353, DOI: 10.1038/nature24286320DNA sequencing at 40: past, present and futureShendure, Jay; Balasubramanian, Shankar; Church, George M.; Gilbert, Walter; Rogers, Jane; Schloss, Jeffery A.; Waterston, Robert H.Nature (London, United Kingdom) (2017), 550 (7676), 345-353CODEN: NATUAS; ISSN:0028-0836. (Nature Research)This review commemorates the 40th anniversary of DNA sequencing, a period in which we have already witnessed multiple technol. revolutions and a growth in scale from a few kilobases to the first human genome, and now to millions of human and a myriad of other genomes. DNA sequencing has been extensively and creatively repurposed, including as a 'counter' for a vast range of mol. phenomena. We predict that in the long view of history, the impact of DNA sequencing will be on a par with that of the microscope.
- 321Alfaro, J. A.; Bohlander, P.; Dai, M.; Filius, M.; Howard, C. J.; van Kooten, X. F.; Ohayon, S.; Pomorski, A.; Schmid, S.; Aksimentiev, A.; Anslyn, E. V.; Bedran, G.; Cao, C.; Chinappi, M.; Coyaud, E.; Dekker, C.; Dittmar, G.; Drachman, N.; Eelkema, R.; Goodlett, D.; Hentz, S.; Kalathiya, U.; Kelleher, N. L.; Kelly, R. T.; Kelman, Z.; Kim, S. H.; Kuster, B.; Rodriguez-Larrea, D.; Lindsay, S.; Maglia, G.; Marcotte, E. M.; Marino, J. P.; Masselon, C.; Mayer, M.; Samaras, P.; Sarthak, K.; Sepiashvili, L.; Stein, D.; Wanunu, M.; Wilhelm, M.; Yin, P.; Meller, A.; Joo, C. The emerging landscape of single-molecule protein sequencing technologies. Nat. Methods 2021, 18, 604– 617, DOI: 10.1038/s41592-021-01143-1321The emerging landscape of single-molecule protein sequencing technologiesAlfaro, Javier Antonio; Bohlander, Peggy; Dai, Mingjie; Filius, Mike; Howard, Cecil J.; van Kooten, Xander F.; Ohayon, Shilo; Pomorski, Adam; Schmid, Sonja; Aksimentiev, Aleksei; Anslyn, Eric V.; Bedran, Georges; Cao, Chan; Chinappi, Mauro; Coyaud, Etienne; Dekker, Cees; Dittmar, Gunnar; Drachman, Nicholas; Eelkema, Rienk; Goodlett, David; Hentz, Sebastien; Kalathiya, Umesh; Kelleher, Neil L.; Kelly, Ryan T.; Kelman, Zvi; Kim, Sung Hyun; Kuster, Bernhard; Rodriguez-Larrea, David; Lindsay, Stuart; Maglia, Giovanni; Marcotte, Edward M.; Marino, John P.; Masselon, Christophe; Mayer, Michael; Samaras, Patroklos; Sarthak, Kumar; Sepiashvili, Lusia; Stein, Derek; Wanunu, Meni; Wilhelm, Mathias; Yin, Peng; Meller, Amit; Joo, ChirlminNature Methods (2021), 18 (6), 604-617CODEN: NMAEA3; ISSN:1548-7091. (Nature Portfolio)Single-cell profiling methods have had a profound impact on the understanding of cellular heterogeneity. While genomes and transcriptomes can be explored at the single-cell level, single-cell profiling of proteomes is not yet established. Here we describe new single-mol. protein sequencing and identification technologies alongside innovations in mass spectrometry that will eventually enable broad sequence coverage in single-cell profiling. These technologies will in turn facilitate biol. discovery and open new avenues for ultrasensitive disease diagnostics.
- 322Zhao, Y. Q.; Iarossi, M.; De Fazio, A. F.; Huang, J. A.; De Angelis, F. Label-Free Optical Analysis of Biomolecules in Solid-State Nanopores: Toward Single-Molecule Protein Sequencing. Acs Photonics 2022, 9, 730– 742, DOI: 10.1021/acsphotonics.1c01825322Label-Free Optical Analysis of Biomolecules in Solid-State Nanopores: Toward Single-Molecule Protein SequencingZhao, Yingqi; Iarossi, Marzia; De Fazio, Angela Federica; Huang, Jian-An; De Angelis, FrancescoACS Photonics (2022), 9 (3), 730-742CODEN: APCHD5; ISSN:2330-4022. (American Chemical Society)Sequence identification of peptides and proteins is central to proteomics. Protein sequencing is mainly conducted by insensitive mass spectroscopy because proteins cannot be amplified, which hampers applications such as single-cell proteomics and precision medicine. The com. success of portable nanopore sequencers for single DNA mols. has inspired extensive research and development of single-mol. techniques for protein sequencing. Among them, three challenges remain: (1) discrimination of the 20 amino acids as building blocks of proteins; (2) unfolding proteins; and (3) controlling the motion of proteins with nonuniformly charged sequences. In this context, the emergence of label-free optical anal. techniques for single amino acids and peptides by solid-state nanopores shows promise for addressing the first challenge. In this Perspective, we first discuss the current challenges of single-mol. fluorescence detection and nanopore resistive pulse sensing in a protein sequencing. Then, label-free optical methods are described to show how they address the single-amino-acid identification within single peptides. They include localized surface plasmon resonance detection and surface-enhanced Raman spectroscopy on plasmonic nanopores. Notably, we report new data to show the ability of plasmon-enhanced Raman scattering to record and discriminate the 20 amino acids at a single-mol. level. In addn., we discuss briefly the manipulation of mol. translocation and liq. flow in plasmonic nanopores for controlling mol. movement to allow high-resoln. reading of protein sequences. We envision that a combination of Raman spectroscopy with plasmonic nanopores can succeed in single-mol. protein sequencing in a label-free way.
- 323Huang, J.-A.; Mousavi, M. Z.; Zhao, Y.; Hubarevich, A.; Omeis, F.; Giovannini, G.; Schütte, M.; Garoli, D.; De Angelis, F. SERS discrimination of single DNA bases in single oligonucleotides by electro-plasmonic trapping. Nat. Commun. 2019, 10, 5321, DOI: 10.1038/s41467-019-13242-x323SERS discrimination of single DNA bases in single oligonucleotides by electro-plasmonic trappingHuang Jian-An; Mousavi Mansoureh Z; Zhao Yingqi; Hubarevich Aliaksandr; Omeis Fatima; Giovannini Giorgia; Garoli Denis; De Angelis Francesco; Schutte Moritz; Garoli DenisNature communications (2019), 10 (1), 5321 ISSN:.Surface-enhanced Raman spectroscopy (SERS) sensing of DNA bases by plasmonic nanopores could pave a way to novel methods for DNA analyses and new generation single-molecule sequencing platforms. The SERS discrimination of single DNA bases depends critically on the time that a DNA strand resides within the plasmonic hot spot. In fact, DNA molecules flow through the nanopores so rapidly that the SERS signals collected are not sufficient for single-molecule analysis. Here, we report an approach to control the residence time of molecules in the hot spot by an electro-plasmonic trapping effect. By directly adsorbing molecules onto a gold nanoparticle and then trapping the single nanoparticle in a plasmonic nanohole up to several minutes, we demonstrate single-molecule SERS detection of all four DNA bases as well as discrimination of single nucleobases in a single oligonucleotide. Our method can be extended easily to label-free sensing of single-molecule amino acids and proteins.
- 324Chen, C.; Li, Y.; Kerman, S.; Neutens, P.; Willems, K.; Cornelissen, S.; Lagae, L.; Stakenborg, T.; Van Dorpe, P. High spatial resolution nanoslit SERS for single-molecule nucleobase sensing. Nat. Commun. 2018, 9, 1733, DOI: 10.1038/s41467-018-04118-7324High spatial resolution nanoslit SERS for single-molecule nucleobase sensingChen Chang; Li Yi; Kerman Sarp; Neutens Pieter; Willems Kherim; Cornelissen Sven; Lagae Liesbet; Stakenborg Tim; Van Dorpe Pol; Chen Chang; Kerman Sarp; Neutens Pieter; Lagae Liesbet; Van Dorpe Pol; Li Yi; Cornelissen Sven; Willems KherimNature communications (2018), 9 (1), 1733 ISSN:.Solid-state nanopores promise a scalable platform for single-molecule DNA analysis. Direct, real-time identification of nucleobases in DNA strands is still limited by the sensitivity and the spatial resolution of established ionic sensing strategies. Here, we study a different but promising strategy based on optical spectroscopy. We use an optically engineered elongated nanopore structure, a plasmonic nanoslit, to locally enable single-molecule surface enhanced Raman spectroscopy (SERS). Combining SERS with nanopore fluidics facilitates both the electrokinetic capture of DNA analytes and their local identification through direct Raman spectroscopic fingerprinting of four nucleobases. By studying the stochastic fluctuation process of DNA analytes that are temporarily adsorbed inside the pores, we have observed asynchronous spectroscopic behavior of different nucleobases, both individual and incorporated in DNA strands. These results provide evidences for the single-molecule sensitivity and the sub-nanometer spatial resolution of plasmonic nanoslit SERS.
- 325Li, W.; Guo, L.; Ding, X.; Ding, Y.; Ji, L.; Xia, X.; Wang, K. High-Throughput Single-Molecule Surface-Enhanced Raman Spectroscopic Profiling of Single-Amino Acid Substitutions in Peptides by a Gold Plasmonic Nanopore. ACS Nano 2024, 18, 19200– 19207, DOI: 10.1021/acsnano.4c04775There is no corresponding record for this reference.
- 326Iarossi, M.; Darvill, D.; Hubarevich, A.; Huang, J.; Zhao, Y.; De Fazio, A.; O’Neill, D.; Tantussi, F.; De Angelis, F. High-Density Plasmonic Nanopores for DNA Sensing at Ultra-Low Concentrations by Plasmon-Enhanced Raman Spectroscopy. Adv. Funct. Mater. 2023, 33, 2301934, DOI: 10.1002/adfm.202301934There is no corresponding record for this reference.
- 327Huang, J.-A.; Mousavi, M. Z.; Giovannini, G.; Zhao, Y.; Hubarevich, A.; Soler, M. A.; Rocchia, W.; Garoli, D.; De Angelis, F. Multiplexed Discrimination of Single Amino Acid Residues in Polypeptides in a Single SERS Hot Spot. Angew. Chem., Int. Ed. 2020, 59, 11423– 11431, DOI: 10.1002/anie.202000489327Multiplexed Discrimination of Single Amino Acid Residues in Polypeptides in a Single SERS Hot SpotHuang, Jian-An; Mousavi, Mansoureh Z.; Giovannini, Giorgia; Zhao, Yingqi; Hubarevich, Aliaksandr; Soler, Miguel A.; Rocchia, Walter; Garoli, Denis; De Angelis, FrancescoAngewandte Chemie, International Edition (2020), 59 (28), 11423-11431CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)The SERS-based detection of protein sequences with single-residue sensitivity suffers from signal dominance of arom. amino acid residues and backbones, impeding detection of non-arom. amino acid residues. Herein, the authors trap a gold nanoparticle in a plasmonic nanohole to generate a single SERS hot spot for single-mol. detection of 2 similar polypeptides (vasopressin and oxytocin) and 10 distinct amino acids that constitute the 2 polypeptides. Significantly, both arom. and non-arom. amino acids were detected and discriminated at the single-mol. level either at individual amino acid mols. or within the polypeptide chains. Correlated with mol. dynamics simulations, the authors' results suggest that the signal dominance due to large spatial occupancy of arom. rings of the polypeptide sidechains on gold surfaces can be overcome by the high localization of the single hot spot. The superior spectral and spatial discriminative power of the authors' approach can be applied to single-protein anal., fingerprinting, and sequencing.
- 328Ray, T. R.; Choi, J.; Bandodkar, A. J.; Krishnan, S.; Gutruf, P.; Tian, L.; Ghaffari, R.; Rogers, J. A. Bio-Integrated Wearable Systems: A Comprehensive Review. Chem. Rev. 2019, 119, 5461– 5533, DOI: 10.1021/acs.chemrev.8b00573328Bio-Integrated Wearable Systems: A Comprehensive ReviewRay, Tyler R.; Choi, Jungil; Bandodkar, Amay J.; Krishnan, Siddharth; Gutruf, Philipp; Tian, Limei; Ghaffari, Roozbeh; Rogers, John A.Chemical Reviews (Washington, DC, United States) (2019), 119 (8), 5461-5533CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review. Bio-integrated wearable systems can measure a broad range of biophys., biochem., and environmental signals to provide crit. insights into overall health status and to quantify human performance. Recent advances in material science, chem. anal. techniques, device designs, and assembly methods form the foundations for a uniquely differentiated type of wearable technol., characterized by noninvasive, intimate integration with the soft, curved, time-dynamic surfaces of the body. This review summarizes the latest advances in this emerging field of "bio-integrated" technologies in a comprehensive manner that connects fundamental developments in chem., material science, and engineering with sensing technologies that have the potential for widespread deployment and societal benefit in human health care. An introduction to the chemistries and materials for the active components of these systems contextualizes essential design considerations for sensors and assocd. platforms that appear in following sections. The subsequent content highlights the most advanced biosensors, classified according to their ability to capture biophys., biochem., and environmental information. Addnl. sections feature schemes for elec. powering these sensors and strategies for achieving fully integrated, wireless systems. The review concludes with an overview of key remaining challenges and a summary of opportunities where advances in materials chem. will be critically important for continued progress.
- 329Heikenfeld, J.; Jajack, A.; Feldman, B.; Granger, S. W.; Gaitonde, S.; Begtrup, G.; Katchman, B. A. Accessing analytes in biofluids for peripheral biochemical monitoring. Nat. Biotechnol. 2019, 37, 407– 419, DOI: 10.1038/s41587-019-0040-3329Accessing analytes in biofluids for peripheral biochemical monitoringHeikenfeld, Jason; Jajack, Andrew; Feldman, Benjamin; Granger, Steve W.; Gaitonde, Supriya; Begtrup, Gavi; Katchman, Benjamin A.Nature Biotechnology (2019), 37 (4), 407-419CODEN: NABIF9; ISSN:1087-0156. (Nature Research)Peripheral biochem. monitoring involves the use of wearable devices for minimally invasive or noninvasive measurement of analytes in biofluids such as interstitial fluid, saliva, tears and sweat. The goal in most cases is to obtain measurements that serve as surrogates for circulating analyte concns. in blood. Key technol. developments to date include continuous glucose monitors, which use an indwelling sensor needle to measure glucose in interstitial fluid, and device-integrated sweat stimulation for continuous access to analytes in sweat. Further development of continuous sensing technologies through new electrochem. sensing modalities will be a major focus of future research. While there has been much investment in wearable technologies to sense analytes, less effort has been directed to understanding the physiol. of biofluid secretion. Elucidating the underlying biol. is crucial for accelerating technol. progress, as the biofluid itself often presents the greatest challenge in terms of sample vols., secretion rates, filtration, active analyte channels, variable pH and salinity, analyte breakdown and other confounding factors.
- 330Min, J.; Tu, J.; Xu, C.; Lukas, H.; Shin, S.; Yang, Y.; Solomon, S. A.; Mukasa, D.; Gao, W. Skin-Interfaced Wearable Sweat Sensors for Precision Medicine. Chem. Rev. 2023, 123, 5049– 5138, DOI: 10.1021/acs.chemrev.2c00823330Skin-Interfaced Wearable Sweat Sensors for Precision MedicineMin, Jihong; Tu, Jiaobing; Xu, Changhao; Lukas, Heather; Shin, Soyoung; Yang, Yiran; Solomon, Samuel A.; Mukasa, Daniel; Gao, WeiChemical Reviews (Washington, DC, United States) (2023), 123 (8), 5049-5138CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review. Wearable sensors hold great potential in empowering personalized health monitoring, predictive analytics, and timely intervention toward personalized healthcare. Advances in flexible electronics, material sciences, and electrochem. have spurred the development of wearable sweat sensors that enable the continuous and noninvasive screening of analytes indicative of health status. Existing major challenges in wearable sensors include: improving the sweat extn. and sweat sensing capabilities, improving the form factor of the wearable device for minimal discomfort and reliable measurements when worn, and understanding the clin. value of sweat analytes toward biomarker discovery. This review provides a comprehensive review of wearable sweat sensors and outlines state-of-the-art technologies and research that strive to bridge these gaps. The physiol. of sweat, materials, biosensing mechanisms and advances, and approaches for sweat induction and sampling are introduced. Addnl., design considerations for the system-level development of wearable sweat sensing devices, spanning from strategies for prolonged sweat extn. to efficient powering of wearables, are discussed. Furthermore, the applications, data analytics, commercialization efforts, challenges, and prospects of wearable sweat sensors for precision medicine are discussed.
- 331Yang, Y.; Gao, W. Wearable and flexible electronics for continuous molecular monitoring. Chem. Soc. Rev. 2019, 48, 1465– 1491, DOI: 10.1039/C7CS00730B331Wearable and flexible electronics for continuous molecular monitoringYang, Yiran; Gao, WeiChemical Society Reviews (2019), 48 (6), 1465-1491CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)A review. Wearable biosensors have received tremendous attention over the past decade owing to their great potential in predictive analytics and treatment toward personalized medicine. Flexible electronics could serve as an ideal platform for personalized wearable devices because of their unique properties such as light wt., low cost, high flexibility and great conformability. Unlike most reported flexible sensors that mainly track phys. activities and vital signs, the new generation of wearable and flexible chem. sensors enables real-time, continuous and fast detection of accessible biomarkers from the human body, and allows for the collection of large-scale information about the individuals dynamic health status at the mol. level. In this article, we review and highlight recent advances in wearable and flexible sensors toward continuous and non-invasive mol. anal. in sweat, tears, saliva, interstitial fluid, blood, wound exudate as well as exhaled breath. The flexible platforms, sensing mechanisms, and device and system configurations employed for continuous monitoring are summarized. We also discuss the key challenges and opportunities of the wearable and flexible chem. sensors that lie ahead.
- 332Chung, M.; Fortunato, G.; Radacsi, N. Wearable flexible sweat sensors for healthcare monitoring: a review. J. R Soc. Interface 2019, 16, 20190217– 20190217, DOI: 10.1098/rsif.2019.0217332Wearable flexible sweat sensors for healthcare monitoring: a reviewChung, Michael; Fortunato, Giuseppino; Radacsi, NorbertJournal of the Royal Society, Interface (2019), 16 (159), 20190217CODEN: JRSICU; ISSN:1742-5662. (Royal Society)A review. The state-of-the-art in wearable flexible sensors (WFSs) for sweat analyte detection was investigated. Recent advances show the development of integrated, mech. flexible and multiplexed sensor systems with on-site circuitry for signal processing and wireless data transmission. When compared with single-analyte sensors, such devices provide an opportunity to more accurately analyze analytes that are dependent on other parameters (such as sweat rate and pH) by improving calibration from in situ real-time anal., while maintaining a lightwt. and wearable design. Important health conditions can be monitored and on-demand regulating drugs can be delivered using integrated wearable systems but require correlation verification between sweat and blood measurements using in vivo validation tests before any clin. application can be considered. Improvements are necessary for device sensitivity, accuracy and repeatability to provide more reliable and personalized continuous measurements. With rapid recent development, it can be concluded that non-invasive WFSs for sweat anal. have only skimmed the surface of their health monitoring potential and further significant advancement is sure to be made in the medical field.
- 333Suzuki, S.; Yoshimura, M. Chemical Stability of Graphene Coated Silver Substrates for Surface-Enhanced Raman Scattering. Sci. Rep. 2017, 7, 14851, DOI: 10.1038/s41598-017-14782-2333Chemical Stability of Graphene Coated Silver Substrates for Surface-Enhanced Raman ScatteringSuzuki Seiya; Yoshimura MasamichiScientific reports (2017), 7 (1), 14851 ISSN:.Surface enhanced Raman spectroscopy (SERS) is a novel method to sense molecular and lattice vibrations at a high sensitivity. Although nanostructured silver surface provides intense SERS signals, the silver surface is unstable under acidic environment and heated environment. Graphene, a single atomic carbon layer, has a prominent stability for chemical agents, and its honeycomb lattice completely prevents the penetration of small molecules. Here, we fabricated a SERS substrate by combining nanostructured silver surface and single-crystal monolayer graphene (G-SERS), and focused on its chemical stability. The G-SERS substrate showed SERS even in concentrated hydrochloric acid (35-37%) and heated air up to 400 °C, which is hardly obtainable by normal silver SERS substrates. The chemically stable G-SERS substrate posesses a practical and feasible application, and its high chemical stability provides a new type of SERS technique such as molecular detections at high temperatures or in extreme acidic conditions.
- 334Yang, Y.; Liu, J.; Fu, Z.-W.; Qin, D. Galvanic Replacement-Free Deposition of Au on Ag for Core–Shell Nanocubes with Enhanced Chemical Stability and SERS Activity. J. Am. Chem. Soc. 2014, 136, 8153– 8156, DOI: 10.1021/ja502472x334Galvanic Replacement-Free Deposition of Au on Ag for Core-Shell Nanocubes with Enhanced Chemical Stability and SERS ActivityYang, Yin; Liu, Jingyue; Fu, Zheng-Wen; Qin, DongJournal of the American Chemical Society (2014), 136 (23), 8153-8156CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)The authors report a robust synthesis of Ag@Au core-shell nanocubes by directly depositing Au atoms on the surfaces of Ag nanocubes as conformal, ultrathin shells. The success relies on the introduction of a strong reducing agent to compete with and thereby block the galvanic replacement between Ag and HAuCl4. An ultrathin Au shell of 0.6 nm thick was able to protect the Ag in the core in an oxidative environment. Significantly, the core-shell nanocubes exhibited surface plasmonic properties essentially identical to those of the original Ag nanocubes, while the SERS activity showed a 5.4-fold further enhancement owing to an improvement in chem. enhancement. The combination of excellent SERS activity and chem. stability may enable a variety of new applications.
- 335Xiao, J.; Wang, J.; Luo, Y.; Xu, T.; Zhang, X. Wearable Plasmonic Sweat Biosensor for Acetaminophen Drug Monitoring. ACS Sens 2023, 8, 1766– 1773, DOI: 10.1021/acssensors.3c00063335Wearable Plasmonic Sweat Biosensor for Acetaminophen Drug MonitoringXiao, Jingyu; Wang, Jing; Luo, Yong; Xu, Tailin; Zhang, XuejiACS Sensors (2023), 8 (4), 1766-1773CODEN: ASCEFJ; ISSN:2379-3694. (American Chemical Society)Monitoring the acetaminophen dosage is important to prevent the occurrence of adverse reactions such as liver failure and kidney damage. Traditional approaches to monitoring acetaminophen dosage mainly rely on invasive blood collection. Herein, we developed a noninvasive microfluidic-based wearable plasmonic sensor to achieve simultaneous sweat sampling and acetaminophen drug monitoring for vital signs. The fabricated sensor employs an Au nanosphere cone array as the key sensing component, which poses a substrate with surface-enhanced Raman scattering (SERS) activity to noninvasively and sensitively detect the fingerprint of acetaminophen mols. based on its unique SERS spectrum. The developed sensor enabled the sensitive detection and quantification of acetaminophen at concns. as low as 0.13μM. We further evaluated the sweat sensor integrated with a Raman spectrometer for monitoring acetaminophen in drug-administered subjects. These results indicated that the sweat sensor could measure acetaminophen levels and reflect drug metab. The sweat sensors have revolutionized wearable sensing technol. by adopting label-free and sensitive mol. tracking methods for noninvasive and point-of-care drug monitoring and management.
- 336Mogera, U.; Guo, H.; Namkoong, M.; Rahman, M. S.; Nguyen, T.; Tian, L. Wearable plasmonic paper-based microfluidics for continuous sweat analysis. Sci. Adv. 2022, 8, eabn1736, DOI: 10.1126/sciadv.abn1736There is no corresponding record for this reference.
- 337Wang, Y.; Zhao, C.; Wang, J.; Luo, X.; Xie, L.; Zhan, S.; Kim, J.; Wang, X.; Liu, X.; Ying, Y. Wearable plasmonic-metasurface sensor for noninvasive and universal molecular fingerprint detection on biointerfaces. Science Advances 2021, 7, eabe4553, DOI: 10.1126/sciadv.abe4553There is no corresponding record for this reference.
- 338Koh, E. H.; Lee, W. C.; Choi, Y. J.; Moon, J. I.; Jang, J.; Park, S. G.; Choo, J.; Kim, D. H.; Jung, H. S. A Wearable Surface-Enhanced Raman Scattering Sensor for Label-Free Molecular Detection. ACS Appl. Mater. Interfaces 2021, 13, 3024– 3032, DOI: 10.1021/acsami.0c18892338A wearable surface-enhanced raman scattering sensor for label-free molecular detectionKoh, Eun Hye; Lee, Won-Chul; Choi, Yeong-Jin; Moon, Joung-Il; Jang, Jinah; Park, Sung-Gyu; Choo, Jaebum; Kim, Dong-Ho; Jung, Ho SangACS Applied Materials & Interfaces (2021), 13 (2), 3024-3032CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)A wearable surface-enhanced Raman scattering (SERS) sensor has been developed as a patch type to utilize as a mol. sweat sensor. Here, the SERS patch sensor is designed to comprise a sweat-absorbing layer, which is an interface to the human skin, an SERS active layer, and a dermal protecting layer that prevents damage and contaminations. A silk fibroin protein film (SFF) is a basement layer that absorbs aq. solns. and filtrates mols. larger than the nanopores created in the β-sheet matrix of the SFF. On the SFF layer, a plasmonic silver nanowire (AgNW) layer is formed to enhance the Raman signal of the mols. that penetrated through the SERS patch in a label-free method. A transparent dermal protecting layer (DP) allows laser penetration to the AgNW layer enabling Raman measurement through the SERS patch without its detachment from the surface. The mol. detection capability and time-dependent absorption properties of the SERS patch are investigated, and then, the feasibility of its use as a wearable drug detection sweat sensor is demonstrated using 2-fluoro-methamphetamine (2-FMA) on the human cadaver skin. It is believed that the developed SERS patch can be utilized as various flexible and wearable biosensors for healthcare monitoring.
- 339Chung, M.; Skinner, W. H.; Robert, C.; Campbell, C. J.; Rossi, R. M.; Koutsos, V.; Radacsi, N. Fabrication of a Wearable Flexible Sweat pH Sensor Based on SERS-Active Au/TPU Electrospun Nanofibers. ACS Appl. Mater. Interfaces 2021, 13, 51504– 51518, DOI: 10.1021/acsami.1c15238339Fabrication of a Wearable Flexible Sweat pH Sensor Based on SERS-Active Au/TPU Electrospun NanofibersChung, Michael; Skinner, William H.; Robert, Colin; Campbell, Colin J.; Rossi, Rene M.; Koutsos, Vasileios; Radacsi, NorbertACS Applied Materials & Interfaces (2021), 13 (43), 51504-51518CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Development of wearable sensing platforms is essential for the advancement of continuous health monitoring and point-of-care testing. Eccrine sweat pH is an analyte that can be noninvasively measured and used to diagnose and aid in monitoring a wide range of physiol. conditions. Surface-enhanced Raman scattering (SERS) offers a rapid, optical technique for fingerprinting of biomarkers present in sweat. In this paper, a mech. flexible, nanofibrous, SERS-active substrate was fabricated by a combination of electrospinning of thermoplastic polyurethane (TPU) and Au sputter coating. This substrate was then investigated for suitability toward wearable sweat pH sensing after functionalization with two commonly used pH-responsive mols., 4-mercaptobenzoic acid (4-MBA), and 4-mercaptopyridine (4-MPy). The developed SERS pH sensor was found to have good resoln. (0.14 pH units for 4-MBA; 0.51 pH units for 4-MPy), with only 1μL of sweat required for a measurement, and displayed no statistically significant difference in performance after 35 days (p = 0.361). Addnl., the Au/TPU nanofibrous SERS pH sensors showed fast sweat-absorbing ability as well as good repeatability and reversibility. The proposed methodol. offers a facile route for the fabrication of SERS substrates which could also be used to measure a wide range of health biomarkers beyond sweat pH.
- 340Liu, L.; Martinez Pancorbo, P.; Xiao, T. H.; Noguchi, S.; Marumi, M.; Segawa, H.; Karhadkar, S.; Gala de Pablo, J.; Hiramatsu, K.; Kitahama, Y.; Itoh, T.; Qu, J.; Takei, K.; Goda, K. Highly Scalable, Wearable Surface-Enhanced Raman Spectroscopy. Advanced Optical Materials 2022, 10, 2200054, DOI: 10.1002/adom.202200054340Highly Scalable, Wearable Surface-Enhanced Raman SpectroscopyLiu, Limei; Martinez Pancorbo, Pablo; Xiao, Ting-Hui; Noguchi, Saya; Marumi, Machiko; Segawa, Hiroki; Karhadkar, Siddhant; Gala de Pablo, Julia; Hiramatsu, Kotaro; Kitahama, Yasutaka; Itoh, Tamitake; Qu, Junle; Takei, Kuniharu; Goda, KeisukeAdvanced Optical Materials (2022), 10 (17), 2200054CODEN: AOMDAX; ISSN:2195-1071. (Wiley-VCH Verlag GmbH & Co. KGaA)The last two decades have witnessed a dramatic growth of wearable sensor technol., mainly represented by flexible, stretchable, on-skin electronic sensors that provide rich information of the wearer's health conditions and surroundings. A recent breakthrough in the field is the development of wearable chem. sensors based on surface-enhanced Raman spectroscopy (SERS) that can detect mol. fingerprints universally, sensitively, and noninvasively. However, while their sensing properties are excellent, these sensors are not scalable for widespread use beyond small-scale human health monitoring due to their cumbersome fabrication process and limited multifunctional sensing capabilities. Here, a highly scalable, wearable SERS sensor is demonstrated based on an easy-to-fabricate, low-cost, ultrathin, flexible, stretchable, adhesive, and biointegratable gold nanomesh. It can be fabricated in any shape and worn on virtually any surface for label-free, large-scale, in situ sensing of diverse analytes from low to high concns. (10-106 x 10-9M). To show the practical utility of the wearable SERS sensor, the sensor is tested for the detection of sweat biomarkers, drugs of abuse, and microplastics. This wearable SERS sensor represents a significant step toward the generalizability and practicality of wearable sensing technol.
- 341He, X.; Fan, C.; Luo, Y.; Xu, T.; Zhang, X. Flexible microfluidic nanoplasmonic sensors for refreshable and portable recognition of sweat biochemical fingerprint. npj Flexible Electronics 2022, 6, 60, DOI: 10.1038/s41528-022-00192-6341Flexible microfluidic nanoplasmonic sensors for refreshable and portable recognition of sweat biochemical fingerprintHe, Xuecheng; Fan, Chuan; Luo, Yong; Xu, Tailin; Zhang, Xuejinpj Flexible Electronics (2022), 6 (1), 60CODEN: NFEPB8; ISSN:2397-4621. (Nature Portfolio)Wearable sweat sensors with various sensing systems can provide noninvasive medical diagnostics and healthcare monitoring. Here, we demonstrate a wearable microfluidic nanoplasmonic sensor capable of refreshable and portable recognition fingerprint information of targeted biomarkers including urea, lactate, and pH in sweat. A miniature, thin plasmonic metasurface with homogeneous mushroom-shaped hot spots and high surface-enhanced Raman scattering (SERS) activity is designed and integrated into a microfluidics platform. Compared to conventional wearable SERS platforms with the risk of mixed effect between new and old sweat, the microfluidic SERS system allows sweat administration in a controllable and high temporal-resoln. fashion, providing refreshable SERS anal. We use a portable and customized Raman analyzer with a friendly human-machine interface for portable recognition of the spectroscopic signatures of sweat biomarkers. This study integrates epidermal microfluidics with portable SERS mol. recognition, presenting a controllable, handy, and dynamical biofluid sensing system for personalized medicine.
- 342Zhu, K.; Yang, K.; Zhang, Y.; Yang, Z.; Qian, Z.; Li, N.; Li, L.; Jiang, G.; Wang, T.; Zong, S.; Wu, L.; Wang, Z.; Cui, Y. Wearable SERS Sensor Based on Omnidirectional Plasmonic Nanovoids Array with Ultra-High Sensitivity and Stability. Small 2022, 18, e2201508, DOI: 10.1002/smll.202201508342Wearable SERS Sensor Based on Omnidirectional Plasmonic Nanovoids Array with Ultra-High Sensitivity and StabilityZhu, Kai; Yang, Kuo; Zhang, Yizhi; Yang, Zhaoyan; Qian, Ziting; Li, Na; Li, Lang; Jiang, Guohua; Wang, Tingyu; Zong, Shenfei; Wu, Lei; Wang, Zhuyuan; Cui, YipingSmall (2022), 18 (32), 2201508CODEN: SMALBC; ISSN:1613-6810. (Wiley-VCH Verlag GmbH & Co. KGaA)Surface-enhanced Raman spectroscopy (SERS) is a promising technol. for wearable sensors due to its fingerprint spectrum and high detection sensitivity. However, since SERS-activity is sensitive to both the distribution of "hotspots" and excitation angle, it is profoundly challenging to develop a wearable SERS sensor with high stability under various deformations during movements. Herein, inspired by omnidirectional light-harvesting of the compd. eye of Xenos Peckii, a wearable SERS sensor is developed using omnidirectional plasmonic nanovoids array (OPNA), which is prepd. by assembling a monolayer of metal nanoparticles into the artificial plasmonic compd.-eye (APC). Specifically, APC is an interconnected frame contg. omnidirectional "pockets" and acts as an "armour", not only rendering a broadband and omnidirectional enhancement of "hotspots" in the delicate nanoparticles array, but also maintaining an integrity of the "hotspots" against external mech. deformations. Furthermore, an asymmetry super-hydrophilic pattern is fabricated on the surface of OPNA, endowing the hydrophobic OPNA with the ability to spontaneously ext. and conc. the analytes from sweat. Such an armored SERS sensor can enable the wearable and in situ anal. with high sensitivity and stability, exhibiting great potential in point-of-care anal.
- 343Lee, C. H.; Hankus, M. E.; Tian, L.; Pellegrino, P. M.; Singamaneni, S. Highly Sensitive Surface Enhanced Raman Scattering Substrates Based on Filter Paper Loaded with Plasmonic Nanostructures. Anal. Chem. 2011, 83, 8953– 8958, DOI: 10.1021/ac2016882343Highly Sensitive Surface Enhanced Raman Scattering Substrates Based on Filter Paper Loaded with Plasmonic NanostructuresLee, Chang H.; Hankus, Mikella E.; Tian, Limei; Pellegrino, Paul M.; Singamaneni, SrikanthAnalytical Chemistry (Washington, DC, United States) (2011), 83 (23), 8953-8958CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)The authors report a novel surface enhanced Raman scattering (SERS) substrate platform based on a common filter paper adsorbed with plasmonic nanostructures that overcomes many of the challenges assocd. with existing SERS substrates. The paper-based design results in a substrate that combines all of the advantages of conventional rigid and planar SERS substrates in a dynamic flexible scaffolding format. The fabrication, phys. characterization, and SERS activity of the authors' novel substrates using nonresonant analytes are discussed. The SERS substrate is highly sensitive, robust, and amiable to several different environments and target analytes. It is also cost-efficient and demonstrates high sample collection efficiency and does not require complex fabrication methodologies. The paper substrate has high sensitivity (0.5 nM trans-1,2-bis(4-pyridyl)ethene (BPE)) and excellent reproducibility (∼15% relative std. deviation ). The paper substrates demonstrated here establish a novel platform for integrating SERS with already existing anal. techniques such as chromatog. and microfluidics, imparting chem. specificity to these techniques.
- 344Lee, C. H.; Tian, L.; Singamaneni, S. Paper-Based SERS Swab for Rapid Trace Detection on Real-World Surfaces. ACS Appl. Mater. Interfaces 2010, 2, 3429– 3435, DOI: 10.1021/am1009875344Paper-based SERS swab for rapid trace detection on real-world surfacesLee, Chang H.; Tian, Limei; Singamaneni, SrikanthACS Applied Materials & Interfaces (2010), 2 (12), 3429-3435CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)One of the important but often overlooked considerations in the design of surface-enhanced Raman scattering (SERS) substrates for trace detection is the efficiency of sample collection. Conventional designs based on rigid substrates such as silicon, alumina, and glass resist conformal contact with the surface under study, making the sample collection inefficient. The authors demonstrate a novel SERS substrate based on common filter paper adsorbed with gold nanorods, which allows conformal contact with real-world surfaces, thus dramatically enhancing the sample collection efficiency compared to conventional rigid substrates. The authors demonstrate the detection of trace amts. of analyte (140 pg spread over 4 cm2) by simply swabbing the surface under study with the novel SERS substrate. The hierarchical fibrous structure of paper serves as a 3-dimensional vasculature for easy uptake and transport of the analytes to the electromagnetic hot spots. Simple yet highly efficient and cost-effective SERS substrate demonstrated here brings SERS-based trace detection closer to real-world applications.
- 345Liu, X.; Li, T.; Lee, T. C.; Sun, Y.; Liu, Y.; Shang, L.; Han, Y.; Deng, W.; Yuan, Z.; Dang, A. Wearable Plasmonic Sensors Engineered via Active-Site Maximization of TiVC MXene for Universal Physiological Monitoring at the Molecular Level. ACS Sens 2024, 9, 483– 493, DOI: 10.1021/acssensors.3c02285345Wearable Plasmonic Sensors Engineered via Active-Site Maximization of TiVC MXene for Universal Physiological Monitoring at the Molecular LevelLiu, Xin; Li, Tiehu; Lee, Tung-Chun; Sun, Yiting; Liu, Yuhui; Shang, Li; Han, Yanying; Deng, Weibin; Yuan, Zeqi; Dang, AleiACS Sensors (2024), 9 (1), 483-493CODEN: ASCEFJ; ISSN:2379-3694. (American Chemical Society)Two-dimensional transition metal carbon/nitrides (MXenes) are promising candidates to revolutionize next-generation wearable sensors as high-performance surface-enhanced Raman scattering (SERS) substrates. However, low sensitivity of pure MXene nanosheets and weak binding force or uncontrolled in situ growth of plasmonic nanoparticles on hybrid MXene composites limit their progress toward universal and reliable sensors. Herein, we designed and manufd. a highly sensitive, structurally stable wearable SERS sensor by in situ fabrication of plasmonic nanostructures on the flexible TiVC membranes via the maximization of chem. reducing sites using alk. treatment. DFT calcns. and exptl. characterization demonstrated that the hydroxyl functional groups on the surface of MXenes can facilitate the redn. of metal precursors and the nucleation of gold nanoparticles (AuNPs) and can be covalently attached to AuNPs. Thus, the fabricated flexible TiVC-OH-Au sensor satisfied the rigorous mech. requirements for wearable sensors. In addn., combining the electromagnetic (EM) enhancement from dense AuNPs formed by the activation of nucleation sites and charge transfer (CT) between target mol. and substrate induced by the abundant DOS near the Fermi level of TiVC, the fabricated sensor exhibits ultrasensitivity, long-term stability, good signal repeatability, and excellent mech. durability. Moreover, the proof-of-concept application of the wearable SERS sensor in sweat sensing was demonstrated to monitor the content of nicotine, methotrexate, nikethamide, and 6-acetylmorphine in sweat at the mol. level, which was an important step toward the universality and practicality of the wearable sensing technol.
- 346Nergiz, S. Z.; Gandra, N.; Farrell, M. E.; Tian, L. M.; Pellegrino, P. M.; Singamaneni, S. Biomimetic SERS substrate: peptide recognition elements for highly selective chemical detection in chemically complex media. J. Mater. Chem. A 2013, 1, 6543– 6549, DOI: 10.1039/c3ta00138e346Biomimetic SERS substrate: peptide recognition elements for highly selective chemical detection in chemically complex mediaNergiz, Saide Z.; Gandra, Naveen; Farrell, Mikella E.; Tian, Limei; Pellegrino, Paul M.; Singamaneni, SrikanthJournal of Materials Chemistry A: Materials for Energy and Sustainability (2013), 1 (22), 6543-6549CODEN: JMCAET; ISSN:2050-7496. (Royal Society of Chemistry)Surface enhanced Raman scattering (SERS) is rapidly emerging as a sensitive transduction platform for the trace detection of chem. and biol. analytes. A crit. challenge that needs to be addressed to propel this technique into real world applications is the poor chem. selectivity of the existing SERS substrates. The authors demonstrate a novel biomimetic approach to enhance the selectivity of plasmonic nanostructures to target chem. analytes. In particular, material-binding peptides, identified through phage-display, serve as recognition elements for selective capture of target chem. species from a complex chem. mixt. As a proof of concept, a nitroarom. explosive mol., trinitrotoluene (TNT), can be detected down to 100 pM concn. even in a complex org. chem. mixt. This ultrasensitive and selective detection is enabled by TNT-binding peptides appended to Au nanorods, which serve as selective SERS media. To the best of the authors' knowledge, this is the 1st demonstration of a biomimetic SERS substrate facilitating selective and sensitive detection of a target chem. analyte in the presence of numerous unknown interfering species.
- 347Tian, L.; Jiang, Q.; Liu, K.-K.; Luan, J.; Naik, R. R.; Singamaneni, S. Bacterial Nanocellulose-Based Flexible Surface Enhanced Raman Scattering Substrate. Advanced Materials Interfaces 2016, 3, 1600214, DOI: 10.1002/admi.201670073There is no corresponding record for this reference.
- 348Tian, L.; Luan, J.; Liu, K.-K.; Jiang, Q.; Tadepalli, S.; Gupta, M. K.; Naik, R. R.; Singamaneni, S. Plasmonic Biofoam: A Versatile Optically Active Material. Nano Lett. 2016, 16, 609– 616, DOI: 10.1021/acs.nanolett.5b04320348Plasmonic Biofoam: A Versatile Optically Active MaterialTian, Limei; Luan, Jingyi; Liu, Keng-Ku; Jiang, Qisheng; Tadepalli, Sirimuvva; Gupta, Maneesh K.; Naik, Rajesh R.; Singamaneni, SrikanthNano Letters (2016), 16 (1), 609-616CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)The authors demonstrate a simple method to create plasmonically active three-dimensional biofoams by integrating plasmonic nanostructures with highly porous biomaterial aerogels. Plasmonic biofoam is a versatile optically active platform that can be harnessed for numerous applications including (i) ultrasensitive chem. detection using surface-enhanced Raman scattering; (ii) highly efficient energy harvesting and steam generation through plasmonic photothermal heating; and (iii) optical control of enzymic activity by triggered release of biomols. encapsulated within the aerogel. 3D plasmonic biofoam exhibits significantly higher sensing, photothermal, and loading efficiency compared to conventional 2D counterparts.
- 349Tian, L.; Morrissey, J. J.; Kattumenu, R.; Gandra, N.; Kharasch, E. D.; Singamaneni, S. Bioplasmonic Paper as a Platform for Detection of Kidney Cancer Biomarkers. Anal. Chem. 2012, 84, 9928– 9934, DOI: 10.1021/ac302332g349Bioplasmonic Paper as a Platform for Detection of Kidney Cancer BiomarkersTian, Limei; Morrissey, Jeremiah J.; Kattumenu, Ramesh; Gandra, Naveen; Kharasch, Evan D.; Singamaneni, SrikanthAnalytical Chemistry (Washington, DC, United States) (2012), 84 (22), 9928-9934CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)We demonstrate that a common lab. filter paper uniformly adsorbed with biofunctionalized plasmonic nanostructures can serve as a highly sensitive transduction platform for rapid detection of trace bioanalytes in physiol. fluids. In particular, we demonstrate that bioplasmonic paper enables rapid urinalysis for the detection of kidney cancer biomarkers in artificial urine down to a concn. of 10 ng/mL. Compared to conventional rigid substrates, bioplasmonic paper offers numerous advantages such as high sp. surface area (resulting in large dynamic range), excellent wicking properties (naturally microfluidic), mech. flexibility, compatibility with conventional printing approaches (enabling multiplexed detection and multimarker biochips), and significant cost redn.
- 350Tian, L.; Tadepalli, S.; Hyun Park, S.; Liu, K.-K.; Morrissey, J. J.; Kharasch, E. D.; Naik, R. R.; Singamaneni, S. Bioplasmonic calligraphy for multiplexed label-free biodetection. Biosens. Bioelectron. 2014, 59, 208– 215, DOI: 10.1016/j.bios.2014.03.043350Bioplasmonic calligraphy for multiplexed label-free biodetectionTian, Limei; Tadepalli, Sirimuvva; Park, Sang Hyun; Liu, Keng-Ku; Morrissey, Jeremiah J.; Kharasch, Evan D.; Naik, Rajesh R.; Singamaneni, SrikanthBiosensors & Bioelectronics (2014), 59 (), 208-215CODEN: BBIOE4; ISSN:0956-5663. (Elsevier B.V.)Printable multi-marker biochips that enable simultaneous quant. detection of multiple target biomarkers in point-of-care and resource-limited settings are a holy grail in the field of biodiagnostics. However, preserving the functionality of biomols., which are routinely employed as recognition elements, during conventional printing approaches remains challenging. In this article, we introduce a simple yet powerful approach, namely plasmonic calligraphy, for realizing multiplexed label-free bioassays. Plasmonic calligraphy involves a regular ballpoint pen filled with biofunctionalized gold nanorods as plasmonic ink for creating isolated test domains on paper substrates. Biofriendly plasmonic calligraphy approach serves as a facile method to miniaturize the test domain size to few mm2, which significantly improves the sensitivity of the plasmonic biosensor compared to bioplasmonic paper fabricated using immersion approach. Furthermore, plasmonic calligraphy also serves as a simple and efficient means to isolate multiple test domains on a single test strip, which facilitates multiplexed biodetection and multi-marker biochips. Plasmonic calligraphy, which can be potentially automated by implementing with a robotic arm, serves as an alternate path forward to overcome the limitations of conventional ink-jet printing.
- 351Tian, L. M.; Tadepalli, S.; Farrell, M. E.; Liu, K. K.; Gandra, N.; Pellegrino, P. M.; Singamaneni, S. Multiplexed charge-selective surface enhanced Raman scattering based on plasmonic calligraphy. J. Mater. Chem. C 2014, 2, 5438– 5446, DOI: 10.1039/c4tc00768a351Multiplexed charge-selective surface enhanced Raman scattering based on plasmonic calligraphyTian, Limei; Tadepalli, Sirimuvva; Farrell, Mikella E.; Liu, Keng-Ku; Gandra, Naveen; Pellegrino, Paul M.; Singamaneni, SrikanthJournal of Materials Chemistry C: Materials for Optical and Electronic Devices (2014), 2 (27), 5438-5446CODEN: JMCCCX; ISSN:2050-7534. (Royal Society of Chemistry)Multiplexed surface enhanced Raman scattering (SERS) substrates, which enable chem. selective detection of two or more target analytes from a complex chem. mixt., are highly attractive for chem. detection in real-world settings. We introduce a new approach called plasmonic calligraphy that involves the formation of chem. selective test domains on paper substrates using functionalized plasmonic nanostructures as ink in a regular ballpoint pen. We demonstrate selective detection of pos. and neg. charged analytes (rhodamine 6G and methyl orange) from complex chem. mixts. using polyelectrolyte-coated gold nanorods as SERS medium. The approach demonstrated here obviates the need for complex patterning techniques such as photolithog. to create isolated test domains on paper substrates for multiplexed chem. detection. Plasmonic calligraphy can be easily extended to other shape-controlled nanostructures with different surface functionalities and potentially automated by implementation with a robotic arm.
- 352Yin, Z.; Guo, H.; Li, Y.; Chiu, J.; Tian, L. Ultrastable Plasmonic Bioink for Printable Point-Of-Care Biosensors. ACS Appl. Mater. Interfaces 2020, 12, 35977– 35985, DOI: 10.1021/acsami.0c11799352Ultrastable Plasmonic Bioink for Printable Point-Of-Care BiosensorsYin, Ze; Guo, Heng; Li, Yixuan; Chiu, Joshua; Tian, LimeiACS Applied Materials & Interfaces (2020), 12 (32), 35977-35985CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Point-of-care biosensors are critically important for early disease diagnosis and timely clin. intervention in resource-limited settings. The real-world application of these biosensors requires the use of stable biol. reagents and cost-effective fabrication approaches. To meet these stringent requirements, the authors introduce a generic encapsulation strategy to realize ultrastable plasmonic bioink by encapsulating antibodies with an organosiloxane polymer through in situ polymn. Plasmonic nanostructures serve as sensitive nanotransducers, allowing for label-free biochem. detection. The plasmonic bioink with encapsulated antibodies exhibits excellent thermal, biol., and colloidal stabilities making it compatible with printing process. As a proof-of-concept, the authors demonstrate the printability of the ultrastable plasmonic bioinks on different types of substrates with direct writing techniques. The organosiloxane polymer preserves the biorecognition capabilities of the biosensors under harsh conditions, including elevated temp., exposure to chem./biol. denaturants, and ultrasonic agitation. Plasmonic biochips fabricated with the ultrastable ink exhibit superior stability compared to the biochips with unencapsulated antibodies.
- 353Kant, K.; Beeram, R.; Cao, Y.; dos Santos, P. S. S.; González-Cabaleiro, L.; García-Lojo, D.; Guo, H.; Joung, Y.; Kothadiya, S.; Lafuente, M.; Leong, Y. X.; Liu, Y.; Liu, Y.; Moram, S. S. B.; Mahasivam, S.; Maniappan, S.; Quesada-González, D.; Raj, D.; Weerathunge, P.; Xia, X.; Yu, Q.; Abalde-Cela, S.; Alvarez-Puebla, R. A.; Bardhan, R.; Bansal, V.; Choo, J.; Coelho, L. C. C.; de Almeida, J. M. M. M.; Gómez-Graña, S.; Grzelczak, M.; Herves, P.; Kumar, J.; Lohmueller, T.; Merkoçi, A.; Montaño-Priede, J. L.; Ling, X. Y.; Mallada, R.; Pérez-Juste, J.; Pina, M. P.; Singamaneni, S.; Soma, V. R.; Sun, M.; Tian, L.; Wang, J.; Polavarapu, L.; Santos, I. P. Plasmonic nanoparticle sensors: current progress, challenges, and future prospects. Nanoscale Horizons 2024, 9, 2085, DOI: 10.1039/D4NH00226AThere is no corresponding record for this reference.
- 354Heikenfeld, J.; Jajack, A.; Rogers, J.; Gutruf, P.; Tian, L.; Pan, T.; Li, R.; Khine, M.; Kim, J.; Wang, J.; Kim, J. Wearable sensors: modalities, challenges, and prospects. Lab Chip 2018, 18, 217– 248, DOI: 10.1039/C7LC00914C354Wearable sensors: modalities, challenges, and prospectsHeikenfeld, J.; Jajack, A.; Rogers, J.; Gutruf, P.; Tian, L.; Pan, T.; Li, R.; Khine, M.; Kim, J.; Wang, J.; Kim, J.Lab on a Chip (2018), 18 (2), 217-248CODEN: LCAHAM; ISSN:1473-0189. (Royal Society of Chemistry)Wearable sensors have recently seen a large increase in both research and commercialization. However, success in wearable sensors has been a mix of both progress and setbacks. Most of com. progress has been in smart adaptation of existing mech., elec. and optical methods of measuring the body. This adaptation has involved innovations in how to miniaturize sensing technologies, how to make them conformal and flexible, and in the development of companion software that increases the value of the measured data. However, chem. sensing modalities have experienced greater challenges in com. adoption, esp. for non-invasive chem. sensors. There have also been significant challenges in making significant fundamental improvements to existing mech., elec., and optical sensing modalities, esp. in improving their specificity of detection. Many of these challenges can be understood by appreciating the body's surface (skin) as more of an information barrier than as an information source. With a deeper understanding of the fundamental challenges faced for wearable sensors and of the state-of-the-art for wearable sensor technol., the roadmap becomes clearer for creating the next generation of innovations and breakthroughs.
- 355Tian, L.; Zimmerman, B.; Akhtar, A.; Yu, K. J.; Moore, M.; Wu, J.; Larsen, R. J.; Lee, J. W.; Li, J.; Liu, Y.; Metzger, B.; Qu, S.; Guo, X.; Mathewson, K. E.; Fan, J. A.; Cornman, J.; Fatina, M.; Xie, Z.; Ma, Y.; Zhang, J.; Zhang, Y.; Dolcos, F.; Fabiani, M.; Gratton, G.; Bretl, T.; Hargrove, L. J.; Braun, P. V.; Huang, Y.; Rogers, J. A. Large-area MRI-compatible epidermal electronic interfaces for prosthetic control and cognitive monitoring. Nature Biomedical Engineering 2019, 3, 194– 205, DOI: 10.1038/s41551-019-0347-xThere is no corresponding record for this reference.
- 356Chandra, S.; Li, J.; Afsharipour, B.; Cardona, A. F.; Suresh, N. L.; Tian, L.; Deng, Y.; Zhong, Y.; Xie, Z.; Shen, H.; Huang, Y.; Rogers, J. A.; Rymer, W. Z. Performance Evaluation of a Wearable Tattoo Electrode Suitable for High-Resolution Surface Electromyogram Recording. IEEE Transactions on Biomedical Engineering 2021, 68, 1389– 1398, DOI: 10.1109/TBME.2020.3032354There is no corresponding record for this reference.
- 357Zhang, H.; Zhao, H.; Zhao, X.; Xu, C.; Franklin, D.; Vázquez-Guardado, A.; Bai, W.; Zhao, J.; Li, K.; Monti, G.; Lu, W.; Kobeissi, A.; Tian, L.; Ning, X.; Yu, X.; Mehta, S.; Chanda, D.; Huang, Y.; Xu, S.; Perez White, B. E.; Rogers, J. A. Biocompatible Light Guide-Assisted Wearable Devices for Enhanced UV Light Delivery in Deep Skin. Adv. Funct. Mater. 2021, 31, 2100576, DOI: 10.1002/adfm.202100576There is no corresponding record for this reference.
- 358Namkoong, M.; Guo, H.; Rahman, M. S.; Wang, D.; Pfeil, C. J.; Hager, S.; Tian, L. Moldable and transferrable conductive nanocomposites for epidermal electronics. npj Flexible Electronics 2022, 6, 41, DOI: 10.1038/s41528-022-00170-yThere is no corresponding record for this reference.
- 359Deo, K. A.; Jaiswal, M. K.; Abasi, S.; Lokhande, G.; Bhunia, S.; Nguyen, T.-U.; Namkoong, M.; Darvesh, K.; Guiseppi-Elie, A.; Tian, L.; Gaharwar, A. K. Nanoengineered Ink for Designing 3D Printable Flexible Bioelectronics. ACS Nano 2022, 16, 8798– 8811, DOI: 10.1021/acsnano.1c09386359Nanoengineered Ink for Designing 3D Printable Flexible BioelectronicsDeo, Kaivalya A.; Jaiswal, Manish K.; Abasi, Sara; Lokhande, Giriraj; Bhunia, Sukanya; Nguyen, Thuy-Uyen; Namkoong, Myeong; Darvesh, Kamran; Guiseppi-Elie, Anthony; Tian, Limei; Gaharwar, Akhilesh K.ACS Nano (2022), 16 (6), 8798-8811CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Flexible electronics require elastomeric and conductive biointerfaces with native tissue-like mech. properties. The conventional approaches to engineer such a biointerface often utilize conductive nanomaterials in combination with polymeric hydrogels that are cross-linked using toxic photoinitiators. Moreover, these systems frequently demonstrate poor biocompatibility and face trade-offs between cond. and mech. stiffness under physiol. conditions. To address these challenges, we developed a class of shear-thinning hydrogels as biomaterial inks for 3D printing flexible bioelectronics. These hydrogels are engineered through a facile vacancy-driven gelation of MoS2 nanoassemblies with naturally derived polymer-thiolated gelatin. Due to shear-thinning properties, these nanoengineered hydrogels can be printed into complex shapes that can respond to mech. deformation. The chem. cross-linked nanoengineered hydrogels demonstrate a 20-fold rise in compressive moduli and can withstand up to 80% strain without permanent deformation, meeting human anatomical flexibility. The nanoengineered network exhibits high cond., compressive modulus, pseudocapacitance, and biocompatibility. The 3D-printed cross-linked structure demonstrates excellent strain sensitivity and can be used as wearable electronics to detect various motion dynamics. Overall, the results suggest that these nanoengineered hydrogels offer improved mech., electronic, and biol. characteristics for various emerging biomedical applications including 3D-printed flexible biosensors, actuators, optoelectronics, and therapeutic delivery devices.
- 360Roy, S.; Deo, K. A.; Lee, H. P.; Soukar, J.; Namkoong, M.; Tian, L.; Jaiswal, A.; Gaharwar, A. K. 3D Printed Electronic Skin for Strain, Pressure and Temperature Sensing. Adv. Funct. Mater. 2024, 34, 2313575, DOI: 10.1002/adfm.202470121There is no corresponding record for this reference.
- 361Kim, H. S.; Kim, H. J.; Lee, J.; Lee, T.; Yun, J.; Lee, G.; Hong, Y. Hand-Held Raman Spectrometer-Based Dual Detection of Creatinine and Cortisol in Human Sweat Using Silver Nanoflakes. Anal. Chem. 2021, 93, 14996– 15004, DOI: 10.1021/acs.analchem.1c02496361Hand-held Raman spectrometer-based dual detection of creatinine and cortisol in human sweat using silver nanoflakesKim, Hyun Soo; Kim, Hyun Jung; Lee, Jaehun; Lee, Taeha; Yun, Jongsu; Lee, Gyudo; Hong, YoochanAnalytical Chemistry (Washington, DC, United States) (2021), 93 (45), 14996-15004CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)The conventional tissue biopsy method yields isolated snapshots of a narrow region. Therefore, it cannot facilitate comprehensive disease characterization and monitoring. Recently, the detection of tumor-derived components in body fluids-a practice known as liq. biopsy-has attracted increased attention from the biochem. research and clin. application viewpoints. In this vein, surface-enhanced Raman scattering (SERS) has been identified as one of the most powerful liq.-biopsy anal. techniques, owing to its high sensitivity and specificity. Moreover, it affords high-capacity spectral multiplexing for simultaneous target detection and a unique ability to obtain intrinsic biomol.-fingerprint spectra. This paper presents the fabrication of silver nanosnowflakes (SNSFs) using the polyol method and their subsequent dropping onto a hydrophobic filter paper. The SERS substrate, which comprises the SNSFs and hydrophobic filter paper, facilitates the simultaneous detection of creatinine and cortisol in human sweat using a hand-held Raman spectrometer. The proposed SERS system affords Raman spectrometry to be performed on small sample vols. (2μL) to identify the normal and at-risk creatinine and cortisol groups.
- 362Song, S.; Wang, L.; Li, J.; Fan, C.; Zhao, J. Aptamer-based biosensors. TrAC Trends in Analytical Chemistry 2008, 27, 108– 117, DOI: 10.1016/j.trac.2007.12.004362Aptamer-based biosensorsSong, Shiping; Wang, Lihua; Li, Jiang; Fan, Chunhai; Zhao, JianlongTrAC, Trends in Analytical Chemistry (2008), 27 (2), 108-117CODEN: TTAEDJ; ISSN:0165-9936. (Elsevier Ltd.)A review. Nucleic-acid aptamers have attracted intense interest and found wide applications in a range of areas. In this review, we summarize recent advances in the development of aptamer-based biosensors and bioassay methods, most of which have employed electrochem., optical and mass-sensitive anal. techniques. Aptamers exhibit many advantages as recognition elements in biosensing when compared to traditional antibodies. They are small in size, chem. stable and cost effective. More importantly, aptamers offer remarkable flexibility and convenience in the design of their structures, which has led to novel biosensors that have exhibited high sensitivity and selectivity. Recently, the combination of aptamers with novel nanomaterials has significantly improved the performance of aptamer-based sensors, which we also review in this article. In view of the unprecedented advantages brought by aptamers, we expect aptamer-based biosensors to find broad applications in biomedical diagnostics, environmental monitoring and homeland security.
- 363Abbas, A.; Tian, L.; Morrissey, J. J.; Kharasch, E. D.; Singamaneni, S. Hot Spot-Localized Artificial Antibodies for Label-Free Plasmonic Biosensing. Adv. Funct. Mater. 2013, 23, 1789– 1797, DOI: 10.1002/adfm.201202370363Hot Spot-Localized Artificial Antibodies for Label-Free Plasmonic BiosensingAbbas, Abdennour; Tian, Limei; Morrissey, Jeremiah J.; Kharasch, Evan D.; Singamaneni, SrikanthAdvanced Functional Materials (2013), 23 (14), 1789-1797CODEN: AFMDC6; ISSN:1616-301X. (Wiley-VCH Verlag GmbH & Co. KGaA)The development of biomol. imprinting over the last decade has raised promising perspectives in replacing natural antibodies with artificial antibodies. A significant no. of reports have been dedicated to imprinting of org. and inorg. nanostructures, but very few were performed on nanomaterials with a transduction function. Herein, a relatively fast and efficient plasmonic hot spot-localized surface imprinting of gold nanorods using reversible template immobilization and siloxane copolymn. is described. The technique enables a fine control of the imprinting process at the nanometer scale and provides a nanobiosensor with high selectivity and reusability. Proof of concept was established by the detection of neutrophil gelatinase-assocd. lipocalin (NGAL), a biomarker for acute kidney injury, using localized surface plasmon resonance spectroscopy. The work represents a valuable step towards plasmonic nanobiosensors with synthetic antibodies for label-free and cost-efficient diagnostic assays. It is expected that this novel class of surface imprinted plasmonic nanomaterials will open up new possibilities in advancing biomedical applications of plasmonic nanostructures.
- 364Tian, L. M.; Liu, K. K.; Morrissey, J. J.; Gandra, N.; Kharasch, E. D.; Singamaneni, S. Gold nanocages with built-in artificial antibodies for label-free plasmonic biosensing. J. Mater. Chem. B 2014, 2, 167– 170, DOI: 10.1039/C3TB21551B364Gold nanocages with built-in artificial antibodies for label-free plasmonic biosensingTian, Limei; Liu, Keng-Ku; Morrissey, Jeremiah J.; Gandra, Naveen; Kharasch, Evan D.; Singamaneni, SrikanthJournal of Materials Chemistry B: Materials for Biology and Medicine (2014), 2 (2), 167-170CODEN: JMCBDV; ISSN:2050-7518. (Royal Society of Chemistry)We demonstrate that gold nanocages (AuNCs) with built-in artificial antibodies enable the detection of kidney injury biomarker from synthetic urine down to a concn. of 25 ng ml-1. Molecularly imprinted AuNCs exhibit excellent selectivity against numerous interfering urinary proteins and remarkable stability over a wide range of pH and sp. gr.
- 365Garg, M.; Guo, H.; Maclam, E.; Zhanov, E.; Samudrala, S.; Pavlov, A.; Rahman, M. S.; Namkoong, M.; Moreno, J. P.; Tian, L. Molecularly Imprinted Wearable Sensor with Paper Microfluidics for Real-Time Sweat Biomarker Analysis. ACS Appl. Mater. Interfaces 2024, 16, 46113– 46122, DOI: 10.1021/acsami.4c10033There is no corresponding record for this reference.
- 366Wang, W.; Chen, Y.; Xiao, C.; Xiao, S.; Wang, C.; Nie, Q.; Xu, P.; Chen, J.; You, R.; Zhang, G.; Lu, Y. Flexible SERS wearable sensor based on nanocomposite hydrogel for detection of metabolites and pH in sweat. Chemical Engineering Journal 2023, 474, 145953, DOI: 10.1016/j.cej.2023.145953366Flexible SERS wearable sensor based on nanocomposite hydrogel for detection of metabolites and pH in sweatWang, Wenxi; Chen, Yiming; Xiao, Chongxin; Xiao, Siying; Wang, Chuyi; Nie, Qingling; Xu, Peipei; Chen, Jingbo; You, Ruiyun; Zhang, Guifeng; Lu, YudongChemical Engineering Journal (Amsterdam, Netherlands) (2023), 474 (), 145953CODEN: CMEJAJ; ISSN:1385-8947. (Elsevier B.V.)Flexible wearable sensors can detect analytes continuously, in real time, and non-invasively, and their application in human health monitoring has received great attention. However, traditional sensors suffer from insufficient biocompatibility, wearing discomfort, and low detection sensitivity, so hydrogel is introduced as a sensor patch to improve the contact between skin and sensor, and combined with surface-enhanced Raman spectroscopy (SERS) technol. for rapid and sensitive anal. of biomarkers in sweat. Here, a flexible SERS wearable sensor based on a sulfonated cellulose nanocomposite hydrogel (S-CNF-Ag NPs/PAA) was developed. The hydrogel was prepd. by photo-crosslinking of sulfonated cellulose silver nanocomposites (S-CNF-Ag NPs) with acrylic acid (AA), which is a quick and easy prepn. process. The network structure of hydrogel can retain small mols. and adsorb sweat through hydrophilic groups, which diffuse sweat into the hydrogel and can effectively collect the analyses in sweat. The introduction of cellulose and silver nanoparticles not only provides excellent mech. and adhesive properties (toughness of 3790 kJ/m3, interfacial toughness of ∼116.23 J/m2), but also good antimicrobial properties and biocompatibility. The SERS technol. enabled the quant. anal. of metabolites in sweat (the detection limits for urea and uric acid were 63.1 μM and 3.98 μM, resp.) and real-time monitoring of pH. S-CNF-Ag NPs/PAA sensor maintained excellent sensitivity, stability and mech. properties during the detection process, effectively expanding the application of hydrogels in flexible SERS sensing and human health detection.
- 367Zong, C.; Cheng, R.; Chen, F.; Lin, P.; Zhang, M.; Chen, Z.; Li, C.; Yang, C.; Cheng, J.-X. Wide-Field Surface-Enhanced Coherent Anti-Stokes Raman Scattering Microscopy. ACS Photonics 2022, 9, 1042– 1049, DOI: 10.1021/acsphotonics.1c02015367Wide-Field Surface-Enhanced Coherent Anti-Stokes Raman Scattering MicroscopyZong, Cheng; Cheng, Ran; Chen, Fukai; Lin, Peng; Zhang, Meng; Chen, Zhicong; Li, Chuan; Yang, Chen; Cheng, Ji-XinACS Photonics (2022), 9 (3), 1042-1049CODEN: APCHD5; ISSN:2330-4022. (American Chemical Society)Surface-enhanced Raman scattering (SERS) spectroscopy has been used extensively to study biol., chem., and materials. However, point-by-point SERS mapping is time-consuming, taking minutes to hours for large-scale imaging. Here, we report a wide-field surface-enhanced coherent anti-Stokes Raman scattering (WISE-CARS) microscope for monitoring nanotags in live cells and label-free detection of metabolic mols. The WISE-CARS microscope achieves an imaging speed of 120 fps for a field of view of 130μm x 130μm. By spectral focusing of femtosecond lasers, a hyperspectral WISE-CARS stack of 60 frames can be acquired within 0.5 s, where over 1 million Raman spectra are parallelly recorded with a spectral resoln. of 10 cm-1. As applications, we demonstrate time-lapse, three-dimensional (3D) WISE-CARS imaging of nanotags in live cells as well as label-free detection of adenine released from S. aureus.
- 368Becerril-Castro, I. B.; Calderon, I.; Ockova, J.; Liebel, M.; van Hulst, N. F.; Giannini, V.; Alvarez-Puebla, R. A. Direct Modular Printing of Plasmonic Chemosensors. ACS Appl. Mater. Interfaces 2022, 14, 57165– 57170, DOI: 10.1021/acsami.2c17202There is no corresponding record for this reference.
- 369Liebel, M.; Calderon, I.; Pazos-Perez, N.; van Hulst, N. F.; Alvarez-Puebla, R. A. Widefield SERS for High-Throughput Nanoparticle Screening. Angewandte Chemie - International Edition 2022, 61, e202200072, DOI: 10.1002/anie.202200072There is no corresponding record for this reference.
- 370Romo-Herrera, J. M.; Juárez-Moreno, K.; Guerrini, L.; Kang, Y. L.; Feliu, N.; Parak, W. J.; Álvarez-Puebla, R. A. Paper-Based Plasmonic Substrates as Surface-Enhanced Raman Scattering Spectroscopy Platforms for Cell Culture Applications. Materials Today Bio 2021, 11, 100125, DOI: 10.1016/j.mtbio.2021.100125There is no corresponding record for this reference.
- 371Liebel, M.; Pazos-Perez, N.; van Hulst, N. F.; Alvarez-Puebla, R. A. Surface-enhanced Raman scattering holography. Nat. Nanotechnol. 2020, 15, 1005– 1011, DOI: 10.1038/s41565-020-0771-9371Surface-enhanced Raman scattering holographyLiebel, Matz; Pazos-Perez, Nicolas; van Hulst, Niek F.; Alvarez-Puebla, Ramon A.Nature Nanotechnology (2020), 15 (12), 1005-1011CODEN: NNAABX; ISSN:1748-3387. (Nature Research)Nanometric probes based on surface-enhanced Raman scattering (SERS) are promising candidates for all-optical environmental, biol. and technol. sensing applications with intrinsic quant. mol. specificity. However, the effectiveness of SERS probes depends on a delicate trade-off between particle size, stability and brightness that has so far hindered their wide application in SERS imaging methodologies. In this Article, we introduce holog. Raman microscopy, which allows single-shot three-dimensional single-particle localization. We validate our approach by simultaneously performing Fourier transform Raman spectroscopy of individual SERS nanoparticles and Raman holog., using shearing interferometry to ext. both the phase and the amplitude of wide-field Raman images and ultimately localize and track single SERS nanoparticles inside living cells in three dimensions. Our results represent a step towards multiplexed single-shot three-dimensional concn. mapping in many different scenarios, including live cell and tissue interrogation and complex anti-counterfeiting applications.
- 372Lindquist, N. C.; Brolo, A. G. Ultra-High-Speed Dynamics in Surface-Enhanced Raman Scattering. J. Phys. Chem. C 2021, 125, 7523– 7532, DOI: 10.1021/acs.jpcc.0c11150372Ultra-High-Speed Dynamics in Surface-Enhanced Raman ScatteringLindquist, Nathan C.; Brolo, Alexandre G.Journal of Physical Chemistry C (2021), 125 (14), 7523-7532CODEN: JPCCCK; ISSN:1932-7447. (American Chemical Society)A review. In this perspective, we discuss recent observations related to the temporal dynamics of intensities in surface-enhanced Raman scattering (SERS) expts. SERS is a well-established and highly active research field, driven by the potential of the technique in anal. and bioanal. applications. However, there are several fundamental aspects of the effect that still challenge and fascinate researchers in the area. Here we will focus on the recent observation that strong SERS intensity fluctuations (SIFs) are seen when expts. are performed at fast acquisition rates, even when the metal surface is completely covered by an adsorbate. Interestingly, the SIF dynamics indicate bursts of SERS activities that last only a few hundreds of microseconds, followed by a longer period of inactivity. This type of behavior has been obsd. from several systems and configurations, including single metallic nanoshells and nanostars, immobilized colloidal aggregates, nanoparticle-on-a-mirror configurations, and metal-coated microspheres. This diversity suggests that the dynamical behavior is a fundamental characteristic of the SERS effect. Time-dependent at. rearrangements within the confined environment of the SERS hotspots are suggested as the main mechanism driving these fluctuations. The dynamical SERS behavior, revealed with high-speed acquisitions, should provide a new direction for the study of at. reconstruction and single mol. interactions with metallic nanoenvironments with an unprecedented level of detail.
- 373Mueller, N. S.; Arul, R.; Jakob, L. A.; Blunt, M. O.; Földes, T.; Rosta, E.; Baumberg, J. J. Collective Mid-Infrared Vibrations in Surface-Enhanced Raman Scattering. Nano Lett. 2022, 22, 7254– 7260, DOI: 10.1021/acs.nanolett.2c02806373Collective Mid-Infrared Vibrations in Surface-Enhanced Raman ScatteringMueller, Niclas S.; Arul, Rakesh; Jakob, Lukas A.; Blunt, Matthew Oliver; Foldes, Tamas; Rosta, Edina; Baumberg, Jeremy J.Nano Letters (2022), 22 (17), 7254-7260CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)Surface-enhanced Raman scattering (SERS) is typically assumed to occur at individual mols. neglecting intermol. vibrational coupling. Here, we show instead how collective vibrations from IR (IR) coupled dipoles are seen in SERS from mol. monolayers. Mixing IR-active mols. with IR-inactive spacer mols. controls the intermol. sepn. Intermol. coupling leads to vibrational frequency upshifts up to 8 cm-1, tuning with the mixing fraction and IR dipole strength, in excellent agreement with microscopic models and d. functional theory. These cooperative frequency shifts can be used as a ruler to measure intermol. distance and disorder with angstrom resoln. We demonstrate this for photochem. reactions of 4-nitrothiophenol, which depletes the no. of neighboring IR-active mols. and breaks the collective vibration, enabling direct tracking of the reaction. Collective mol. vibrations reshape SERS spectra and need to be considered in the anal. of vibrational spectra throughout anal. chem. and sensing.
- 374Das, S.; Saxena, K.; Tinguely, J. C.; Pal, A.; Wickramasinghe, N. L.; Khezri, A.; Dubey, V.; Ahmad, A.; Perumal, V.; Ahmad, R.; Wadduwage, D. N.; Ahluwalia, B. S.; Mehta, D. S. SERS Nanowire Chip and Machine Learning-Enabled Classification of Wild-Type and Antibiotic-Resistant Bacteria at Species and Strain Levels. ACS Appl. Mater. Interfaces 2023, 15, 24047– 24058, DOI: 10.1021/acsami.3c00612374SERS Nanowire Chip and Machine Learning-Enabled Classification of Wild-Type and Antibiotic-Resistant Bacteria at Species and Strain LevelsDas, Sathi; Saxena, Kanchan; Tinguely, Jean-Claude; Pal, Arijit; Wickramasinghe, Nima L.; Khezri, Abdolrahman; Dubey, Vishesh; Ahmad, Azeem; Perumal, Vivekanandan; Ahmad, Rafi; Wadduwage, Dushan N.; Ahluwalia, Balpreet Singh; Mehta, Dalip SinghACS Applied Materials & Interfaces (2023), 15 (20), 24047-24058CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Antimicrobial resistance (AMR) is a major health threat worldwide and the culture-based bacterial detection methods are slow. Surface-enhanced Raman spectroscopy (SERS) can be used to identify target analytes in real time with sensitivity down to the single-mol. level, providing a promising soln. for the culture-free bacterial detection. We report the fabrication of SERS substrates having tightly packed silver (Ag) nanoparticles loaded onto long silicon nanowires (Si NWs) grown by the metal-assisted chem. etching (MACE) method for the detection of bacteria. The optimized SERS chips exhibited sensitivity down to 10-12 M concn. of R6G mols. and detected reproducible Raman spectra of bacteria down to a concn. of 100 colony forming units (CFU)/mL, which is a thousand times lower than the clin. threshold of bacterial infections like UTI (105 CFU/mL). A Siamese neural network model was used to classify SERS spectra from bacteria specimens. The trained model identified 12 different bacterial species, including those which are causative agents for tuberculosis and urinary tract infection (UTI). Next, the SERS chips and another Siamese neural network model were used to differentiate AMR strains from susceptible strains of Escherichia coli (E. coli). The enhancement offered by SERS chip-enabled acquisitions of Raman spectra of bacteria directly in the synthetic urine by spiking the sample with only 103 CFU/mL E. coli. Thus, the present study lays the ground for the identification and quantification of bacteria on SERS chips, thereby offering a potential future use for rapid, reproducible, label-free, and low limit detection of clin. pathogens.
- 375Pérez-Jiménez, A. I.; Lyu, D.; Lu, Z.; Liu, G.; Ren, B. Surface-enhanced Raman spectroscopy: benefits, trade-offs and future developments. Chemical Science 2020, 11, 4563– 4577, DOI: 10.1039/D0SC00809E375Surface-enhanced Raman spectroscopy: benefits, trade-offs and future developmentsPerez-Jimenez, Ana Isabel; Lyu, Danya; Lu, Zhixuan; Liu, Guokun; Ren, BinChemical Science (2020), 11 (18), 4563-4577CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)Surface-enhanced Raman spectroscopy (SERS) is a vibrational spectroscopy technique with sensitivity down to the single mol. level that provides fine mol. fingerprints, allowing for direct identification of target analytes. Extensive theor. and exptl. research, together with continuous development of nanotechnol., has significantly broadened the scope of SERS and made it a hot research field in chem., physics, materials, biomedicine, and so on. However, SERS has not been developed into a routine anal. technique, and continuous efforts have been made to address the problems preventing its real-world application. The present minireview focuses on analyzing current and potential strategies to tackle problems and realize the SERS performance necessary for translation to practical applications.
- 376Zhao, Z.; Bao, H.; Zhao, Q.; Fu, H.; Zhou, L.; Zhang, H.; Li, Y.; Cai, W. Efficient SERS Response of Porous-ZnO-Covered Gold Nanoarray Chips to Trace Benzene-Volatile Organic Compounds. ACS Appl. Mater. Interfaces 2022, 14, 47999– 48010, DOI: 10.1021/acsami.2c11682376Efficient SERS Response of Porous-ZnO-Covered Gold Nanoarray Chips to Trace Benzene-Volatile Organic CompoundsZhao, Zhipeng; Bao, Haoming; Zhao, Qian; Fu, Hao; Zhou, Le; Zhang, Hongwen; Li, Yue; Cai, WeipingACS Applied Materials & Interfaces (2022), 14 (42), 47999-48010CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Fast and sensitive detection of gaseous volatile org. compds. (VOCs), based on surface-enhanced Raman spectroscopy (SERS), is still a challenge due to their weak interaction with plasmonic metals and overly small Raman scattering cross sections. Herein, we propose a simple strategy to achieve the SERS-based highly efficient detection of trace benzene-VOCs (B-VOCs) based on a composite chip. The composite chip is designed and fabricated via covering the porous zinc oxide on gold nanoarrays by a one-step soln. growth method. Such composite chip shows highly selective capture of gaseous B-VOCs (benzene, toluene, nitrobenzene, xylene, and chlorobenzene, etc.), which leads to the rapid and sensitive SERS responses to them. Typically, this chip can response to gaseous toluene within 30 s, and the lowest detectable concn. is below 10 ppb. Further expts. have revealed that there exists an optimal thickness of the ZnO covering layer for the highly efficient SERS response to the B-VOCs, which is about 150 nm. Also, such a composite chip is recoverable in SERS response and hence reusable. The highly efficient SERS response of the composite chip to the B-VOCs is attributed to the porous structure-enhanced mol. adsorption and the electromagnetic-chem. dual-enhancement mechanism. This work not only presents a practical SERS chip for the efficient detection of the typical B-VOCs but also provides a deep understand the interaction between the B-VOCs and the ZnO as well as the chem. enhancement mechanism.
- 377Rodriguez-Nieves, A. L.; Taylor, M. L.; Wilson, R.; Eldridge, B. K.; Nawalage, S.; Annamer, A.; Miller, H. G.; Alle, M. R.; Gomrok, S.; Zhang, D.; Wang, Y.; Huang, X. Multiplexed Surface Protein Detection and Cancer Classification Using Gap-Enhanced Magnetic-Plasmonic Core-Shell Raman Nanotags and Machine Learning Algorithm. ACS Appl. Mater. Interfaces 2024, 16, 2041– 2057, DOI: 10.1021/acsami.3c13921There is no corresponding record for this reference.
- 378Kho, K. W.; Dinish, U. S.; Kumar, A.; Olivo, M. Frequency Shifts in SERS for Biosensing. ACS Nano 2012, 6, 4892– 4902, DOI: 10.1021/nn300352b378Frequency Shifts in SERS for BiosensingKho, Kiang Wei; Dinish, U. S.; Kumar, Anil; Olivo, MaliniACS Nano (2012), 6 (6), 4892-4902CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)The authors report an observation of a peculiar effect in which the vibrational frequencies of antibody-conjugated SERS-active reporter mols. are shifted in quant. correlation with the concn. of the targeted antigen. The authors attribute the frequency shifts to mech. perturbations in the antibody-reporter complex, as a result of antibody-antigen interaction forces. The authors' observation thus demonstrates the potentiality of an antibody-conjugated SERS-active reporter complex as a SERS-active nanomech. sensor for biodetection. Remarkably, the authors' sensing scheme, despite employing only one antibody, is able to achieve detection sensitivity comparable to that of a conventional sandwich immunoassay. Addnl., the authors have carried out a proof-of-concept study into using multiple 'stress-sensitive' SERS reporters for multiplexed detection of antigen-antibody bindings at the subdiffraction limit. The current work could therefore pave the way to realizing a label-free high-d. protein nanoarray.
- 379Langer, J.; Jimenez de Aberasturi, D.; Aizpurua, J.; Alvarez-Puebla, R. A.; Auguié, B.; Baumberg, J. J.; Bazan, G. C.; Bell, S. E. J.; Boisen, A.; Brolo, A. G.; Choo, J.; Cialla-May, D.; Deckert, V.; Fabris, L.; Faulds, K.; García de Abajo, F. J.; Goodacre, R.; Graham, D.; Haes, A. J.; Haynes, C. L.; Huck, C.; Itoh, T.; Käll, M.; Kneipp, J.; Kotov, N. A.; Kuang, H.; Le Ru, E. C.; Lee, H. K.; Li, J.-F.; Ling, X. Y.; Maier, S. A.; Mayerhöfer, T.; Moskovits, M.; Murakoshi, K.; Nam, J.-M.; Nie, S.; Ozaki, Y.; Pastoriza-Santos, I.; Perez-Juste, J.; Popp, J.; Pucci, A.; Reich, S.; Ren, B.; Schatz, G. C.; Shegai, T.; Schlücker, S.; Tay, L.-L.; Thomas, K. G.; Tian, Z.-Q.; Van Duyne, R. P.; Vo-Dinh, T.; Wang, Y.; Willets, K. A.; Xu, C.; Xu, H.; Xu, Y.; Yamamoto, Y. S.; Zhao, B.; Liz-Marzán, L. M. Present and Future of Surface-Enhanced Raman Scattering. ACS Nano 2020, 14, 28– 117, DOI: 10.1021/acsnano.9b04224379Present and Future of Surface-Enhanced Raman ScatteringLanger, Judith; Jimenez de Aberasturi, Dorleta; Aizpurua, Javier; Alvarez-Puebla, Ramon A.; Auguie, Baptiste; Baumberg, Jeremy J.; Bazan, Guillermo C.; Bell, Steven E. J.; Boisen, Anja; Brolo, Alexandre G.; Choo, Jaebum; Cialla-May, Dana; Deckert, Volker; Fabris, Laura; Faulds, Karen; Garcia de Abajo, F. Javier; Goodacre, Royston; Graham, Duncan; Haes, Amanda J.; Haynes, Christy L.; Huck, Christian; Itoh, Tamitake; Kall, Mikael; Kneipp, Janina; Kotov, Nicholas A.; Kuang, Hua; Le Ru, Eric C.; Lee, Hiang Kwee; Li, Jian-Feng; Ling, Xing Yi; Maier, Stefan A.; Mayerhofer, Thomas; Moskovits, Martin; Murakoshi, Kei; Nam, Jwa-Min; Nie, Shuming; Ozaki, Yukihiro; Pastoriza-Santos, Isabel; Perez-Juste, Jorge; Popp, Juergen; Pucci, Annemarie; Reich, Stephanie; Ren, Bin; Schatz, George C.; Shegai, Timur; Schlucker, Sebastian; Tay, Li-Lin; Thomas, K. George; Tian, Zhong-Qun; Van Duyne, Richard P.; Vo-Dinh, Tuan; Wang, Yue; Willets, Katherine A.; Xu, Chuanlai; Xu, Hongxing; Xu, Yikai; Yamamoto, Yuko S.; Zhao, Bing; Liz-Marzan, Luis M.ACS Nano (2020), 14 (1), 28-117CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)A review. The discovery of the enhancement of Raman scattering by mols. adsorbed on nanostructured metal surfaces is a landmark in the history of spectroscopic and anal. techniques. Significant exptl. and theor. effort has been directed toward understanding the surface-enhanced Raman scattering (SERS) effect and demonstrating its potential in various types of ultrasensitive sensing applications in a wide variety of fields. In the 45 years since its discovery, SERS has blossomed into a rich area of research and technol., but addnl. efforts are still needed before it can be routinely used anal. and in com. products. In this Review, prominent authors from around the world joined together to summarize the state of the art in understanding and using SERS and to predict what can be expected in the near future in terms of research, applications, and technol. development. This Review is dedicated to SERS pioneer and our coauthor, the late Prof. Richard Van Duyne, whom we lost during the prepn. of this article.
- 380Song, C.; Jiang, X.; Yang, Y.; Zhang, J.; Larson, S.; Zhao, Y.; Wang, L. High-Sensitive Assay of Nucleic Acid Using Tetrahedral DNA Probes and DNA Concatamers with a Surface-Enhanced Raman Scattering/Surface Plasmon Resonance Dual-Mode Biosensor Based on a Silver Nanorod-Covered Silver Nanohole Array. ACS Appl. Mater. Interfaces 2020, 12, 31242– 31254, DOI: 10.1021/acsami.0c08453380High-Sensitive Assay of Nucleic Acid Using Tetrahedral DNA Probes and DNA Concatamers with a Surface-Enhanced Raman Scattering/Surface Plasmon Resonance Dual-Mode Biosensor Based on a Silver Nanorod-Covered Silver Nanohole ArraySong, Chunyuan; Jiang, Xinyu; Yang, Yanjun; Zhang, Jingjing; Larson, Steven; Zhao, Yiping; Wang, LianhuiACS Applied Materials & Interfaces (2020), 12 (28), 31242-31254CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)A novel surface-enhanced Raman scattering/surface plasmon resonance (SERS/SPR) dual-mode biosensor prepd. on a silver nanorod-covered silver nanohole (Ag NR-NH) array by surface modification of tetrahedral DNA probes is proposed for highly sensitive detecting nucleic acids by a special signal amplification strategy of DNA supersandwich. The Ag NR-NH with a large area and uniformly arrayed nanostructure possesses excellent anisotropic extraordinary optical transmission and strong localized surface plasmon resonance, which lead to sensitive SPR response to the change of a local refractive index and strong localized elec. fields for excellent SERS activity. To obtain high sensitivity and specificity, smart tetrahedral DNA probes are immobilized onto the Ag NR-NH array and the DNA supersandwich sensing strategy, including the signal amplification of DNA concatamers, was used. About 10 times signal enhancement for SPR and 4 times for SERS are achieved by this sensing strategy. In the detection of the target DNA in the human serum, the two sensing modes have complementary performances, i.e., the limit of detection for the SPR array is high (0.51 pM), while for SERS, it is low (0.77 fM), but the specificity for SPR is much higher than that of SERS. This improves the robustness of the DNA sensors, and subsequent recovery tests also confirm good reliability of the biosensor. The proposed SERS/SPR dual-mode biosensor has a great potential for high performance and reliable detection of trace disease-related nucleic acid biomarkers in the serum and is a powerful sensing platform for early-stage disease diagnosis.
- 381Tseng, Y. M.; Chen, K. L.; Chao, P. H.; Han, Y. Y.; Huang, N. T. Deep Learning-Assisted Surface-Enhanced Raman Scattering for Rapid Bacterial Identification. ACS Appl. Mater. Interfaces 2023, 15, 26398– 26406, DOI: 10.1021/acsami.3c03212There is no corresponding record for this reference.
- 382Leong, S. X.; Koh, L. K.; Koh, C. S. L.; Phan-Quang, G. C.; Lee, H. K.; Ling, X. Y. In Situ Differentiation of Multiplex Noncovalent Interactions Using SERS and Chemometrics. ACS Appl. Mater. Interfaces 2020, 12, 33421– 33427, DOI: 10.1021/acsami.0c08053382In Situ Differentiation of Multiplex Noncovalent Interactions Using SERS and ChemometricsLeong, Shi Xuan; Koh, Li Keng; Koh, Charlynn Sher Lin; Phan-Quang, Gia Chuong; Lee, Hiang Kwee; Ling, Xing YiACS Applied Materials & Interfaces (2020), 12 (29), 33421-33427CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Probing changes of noncovalent interactions is crucial to study the binding efficiencies and strengths of (bio)mol. complexes. While surface-enhanced Raman scattering (SERS) offers unique mol. fingerprints to examine such interactions in situ, current platforms are only able to recognize hydrogen bonds because of their reliance on manual spectral identification. Here, the authors differentiate multiple intermol. interactions between two interacting species by synergizing plasmonic liq. marble-based SERS platforms, chemometrics, and d. functional theory. Characteristic 3-mercaptobenzoic acid (probe) Raman signals have distinct peak shifts upon hydrogen bonding and ionic interactions with tert-butylamine, a model interacting species. Notably, the authors further quantify the contributions from each noncovalent interaction coexisting in different proportions. As a proof-of-concept, the authors detect and categorize biol. important nucleotide bases based on mol.-specific interactions. This will potentially be useful to study how subtle changes in biomol. interactions affect their structural and binding properties.
- 383Ma, H.; Liu, S.; Zheng, N.; Liu, Y.; Han, X. X.; He, C.; Lu, H.; Zhao, B. Frequency Shifts in Surface-Enhanced Raman Spectroscopy-Based Immunoassays: Mechanistic Insights and Application in Protein Carbonylation Detection. Anal. Chem. 2019, 91, 9376– 9381, DOI: 10.1021/acs.analchem.9b02640383Frequency Shifts in Surface-Enhanced Raman Spectroscopy-Based Immunoassays: Mechanistic Insights and Application in Protein Carbonylation DetectionMa, Hao; Liu, Songlin; Zheng, Naiqing; Liu, Yawen; Han, Xiao Xia; He, Chengyan; Lu, Hui; Zhao, BingAnalytical Chemistry (Washington, DC, United States) (2019), 91 (15), 9376-9381CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Frequency-shift based surface-enhanced Raman spectroscopy (SERS) has exhibited great potential applications in bioanal. chem. and biomedicine in recent years. The basis and the crucial factors detg. frequency shifts are, however, still unclear. Herein, the authors have systematically investigated how solvents, antigens, and antibodies affect the band shifts in SERS-based immunoassays. By applying the charge transfer theory together with the Stark effect and time-dependent d. functional theory (TDDFT) calcn., mechanistic insights into the frequency shifts in immunoreactions is proposed and discussed in detail. Accordingly, the exptl. condition is further optimized and is successfully applied for the first time to detect carbonylated proteins, promising diagnostic biomarkers for human diseases. This study provides theor. guidance for designing SERS frequency shift-based immunoassays and paves a new avenue for further applications of the strategy in clin. diagnosis.
- 384Guo, S.; Popp, J.; Bocklitz, T. Chemometric analysis in Raman spectroscopy from experimental design to machine learning-based modeling. Nat. Protoc 2021, 16, 5426– 5459, DOI: 10.1038/s41596-021-00620-3384Chemometric analysis in Raman spectroscopy from experimental design to machine learning-based modelingGuo, Shuxia; Popp, Jurgen; Bocklitz, ThomasNature Protocols (2021), 16 (12), 5426-5459CODEN: NPARDW; ISSN:1750-2799. (Nature Portfolio)Abstr.: Raman spectroscopy is increasingly being used in biol., forensics, diagnostics, pharmaceutics and food science applications. This growth is triggered not only by improvements in the computational and exptl. setups but also by the development of chemometric techniques. Chemometric techniques are the anal. processes used to detect and ext. information from subtle differences in Raman spectra obtained from related samples. This information could be used to find out, for example, whether a mixt. of bacterial cells contains different species, or whether a mammalian cell is healthy or not. Chemometric techniques include spectral processing (ensuring that the spectra used for the subsequent computational processes are as clean as possible) as well as the statistical anal. of the data required for finding the spectral differences that are most useful for differentiation between, for example, different cell types. For Raman spectra, this anal. process is not yet standardized, and there are many confounding pitfalls. This protocol provides guidance on how to perform a Raman spectral anal.: how to avoid these pitfalls, and strategies to circumvent problematic issues. The protocol is divided into four parts: exptl. design, data preprocessing, data learning and model transfer. We exemplify our workflow using three example datasets where the spectra from individual cells were collected in single-cell mode, and one dataset where the data were collected from a raster scanning-based Raman spectral imaging expt. of mice tissue. Our aim is to help move Raman-based technologies from proof-of-concept studies toward real-world applications.
- 385Lee, H. K.; Koh, C. S.; Lo, W.-S.; Liu, Y.; Phang, I. Y.; Sim, H. Y.; Lee, Y. H.; Phan-Quang, G. C.; Han, X.; Tsung, C.-K.; Ling, X. Y. Applying a Nanoparticle@MOF Interface To Activate an Unconventional Regioselectivity of an Inert Reaction at Ambient Conditions. J. Am. Chem. Soc. 2020, 142, 11521– 11527, DOI: 10.1021/jacs.0c04144385Applying a Nanoparticle@MOF Interface To Activate an Unconventional Regioselectivity of an Inert Reaction at Ambient ConditionsLee, Hiang Kwee; Koh, Charlynn Sher; Lo, Wei-Shang; Liu, Yejing; Phang, In Yee; Sim, Howard Yi; Lee, Yih Hong; Phan-Quang, Gia Chuong; Han, Xuemei; Tsung, Chia-Kuang; Ling, Xing YiJournal of the American Chemical Society (2020), 142 (26), 11521-11527CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Here we design an interface between a metal nanoparticle (NP) and a metal-org. framework (MOF) to activate an inert CO2 carboxylation reaction and in situ monitor its unconventional regioselectivity at the mol. level. Using a Kolbe-Schmitt reaction as model, our strategy exploits the NP@MOF interface to create a pseudo high-pressure CO2 microenvironment over the phenolic substrate to drive its direct C-H carboxylation at ambient conditions. Conversely, Kolbe-Schmitt reactions usually demand high reaction temp. (>125°C) and pressure (>80 atm). Notably, we observe an unprecedented CO2 meta-carboxylation of an arene that was previously deemed impossible in traditional Kolbe-Schmitt reactions. While the phenolic substrate in this study is fixed at the NP@MOF interface to facilitate spectroscopic investigations, free reactants could be activated the same way by the local pressurized CO2 microenvironment. These valuable insights create enormous opportunities in diverse applications including synthetic chem., gas valorization, and greenhouse gas remediation.
- 386Ehrentreich, F.; Sümmchen, L. Spike removal and denoising of Raman spectra by wavelet transform methods. Anal. Chem. 2001, 73, 4364– 4373, DOI: 10.1021/ac0013756386Spike Removal and Denoising of Raman Spectra by Wavelet Transform MethodsEhrentreich, F.; Suemmchen, L.Analytical Chemistry (2001), 73 (17), 4364-4373CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Wavelet decompns. of Raman spectra were studied with respect to their usability for spike removal and denoising of the raw data. Those operations should be performed sequentially. Suppression of spikes is not straightforwardly possible by wavelet transformation; however, the wavelet transform may be used to recognize the spikes by their 1st level detail coeffs. Spike locations could be projected from the details to the approxns. and, further, to appropriate locations of the original spectrum. After spike recognition, those regions will be replaced by interpolated values. To complete processing, denoising is performed with the despiked spectrum by repeated application of wavelet transform methods.
- 387Phillips, G. R.; Harris, J. M. Polynomial filters for data sets with outlying or missing observations: application to charge-coupled-device-detected Raman spectra contaminated by cosmic rays. Anal. Chem. 1990, 62, 2351– 2357, DOI: 10.1021/ac00220a017387Polynomial filters for data sets with outlying or missing observations: application to charge-coupled-device-detected Raman spectra contaminated by cosmic raysPhillips, G. R.; Harris, Joel M.Analytical Chemistry (1990), 62 (21), 2351-7CODEN: ANCHAM; ISSN:0003-2700.Occasionally data sets contain points with excess error so that no information about the underlying signal is available from these observations. Such points should be considered lost and be given no influence on the results. Polynomial filters suitable for smoothing data sets contg. outlying or missing observations are presented. Outliers are 1st identified by their deviation from the trends of the surrounding data, relative to a robust est. of the std. deviation. In the vicinity of an outlying point thus identified, the missing-point filter employs a polynomial fit to the points surrounding, but not including, the outlying or missing point. In the absence of outliers, the procedure reverts to ordinary Savitzky-Golay polynomial filtering. The equations for generating these filters and predicting their statistical properties were derived. Their performance was evaluated on CCD-detected Raman spectra contaminated with cosmic ray events and was compared with nonlinear smoothing algorithms. The linear, missing-point polynomial filters are efficient, both in speed and in ability to bridge gaps in data with minimal distortion.
- 388Guo, S.; Beleites, C.; Neugebauer, U.; Abalde-Cela, S.; Afseth, N. K.; Alsamad, F.; Anand, S.; Araujo-Andrade, C.; Aškrabić, S.; Avci, E.; Baia, M.; Baranska, M.; Baria, E.; Batista de Carvalho, L. A. E.; de Bettignies, P.; Bonifacio, A.; Bonnier, F.; Brauchle, E. M.; Byrne, H. J.; Chourpa, I.; Cicchi, R.; Cuisinier, F.; Culha, M.; Dahms, M.; David, C.; Duponchel, L.; Duraipandian, S.; El-Mashtoly, S. F.; Ellis, D. I.; Eppe, G.; Falgayrac, G.; Gamulin, O.; Gardner, B.; Gardner, P.; Gerwert, K.; Giamarellos-Bourboulis, E. J.; Gizurarson, S.; Gnyba, M.; Goodacre, R.; Grysan, P.; Guntinas-Lichius, O.; Helgadottir, H.; Grošev, V. M.; Kendall, C.; Kiselev, R.; Kölbach, M.; Krafft, C.; Krishnamoorthy, S.; Kubryck, P.; Lendl, B.; Loza-Alvarez, P.; Lyng, F. M.; Machill, S.; Malherbe, C.; Marro, M.; Marques, M. P. M.; Matuszyk, E.; Morasso, C. F.; Moreau, M.; Muhamadali, H.; Mussi, V.; Notingher, I.; Pacia, M. Z.; Pavone, F. S.; Penel, G.; Petersen, D.; Piot, O.; Rau, J. V.; Richter, M.; Rybarczyk, M. K.; Salehi, H.; Schenke-Layland, K.; Schlücker, S.; Schosserer, M.; Schütze, K.; Sergo, V.; Sinjab, F.; Smulko, J.; Sockalingum, G. D.; Stiebing, C.; Stone, N.; Untereiner, V.; Vanna, R.; Wieland, K.; Popp, J.; Bocklitz, T. Comparability of Raman Spectroscopic Configurations: A Large Scale Cross-Laboratory Study. Anal. Chem. 2020, 92, 15745– 15756, DOI: 10.1021/acs.analchem.0c02696388Comparability of Raman Spectroscopic Configurations: A Large Scale Cross-Laboratory StudyGuo, Shuxia; Beleites, Claudia; Neugebauer, Ute; Abalde-Cela, Sara; Afseth, Nils Kristian; Alsamad, Fatima; Anand, Suresh; Araujo-Andrade, Cuauhtemoc; Askrabic, Sonja; Avci, Ertug; Baia, Monica; Baranska, Malgorzata; Baria, Enrico; Batista de Carvalho, Luis A. E.; de Bettignies, Philippe; Bonifacio, Alois; Bonnier, Franck; Brauchle, Eva Maria; Byrne, Hugh J.; Chourpa, Igor; Cicchi, Riccardo; Cuisinier, Frederic; Culha, Mustafa; Dahms, Marcel; David, Catalina; Duponchel, Ludovic; Duraipandian, Shiyamala; El-Mashtoly, Samir F.; Ellis, David I.; Eppe, Gauthier; Falgayrac, Guillaume; Gamulin, Ozren; Gardner, Benjamin; Gardner, Peter; Gerwert, Klaus; Giamarellos-Bourboulis, Evangelos J.; Gizurarson, Sveinbjorn; Gnyba, Marcin; Goodacre, Royston; Grysan, Patrick; Guntinas-Lichius, Orlando; Helgadottir, Helga; Grosev, Vlasta Mohacek; Kendall, Catherine; Kiselev, Roman; Koelbach, Micha; Krafft, Christoph; Krishnamoorthy, Sivashankar; Kubryck, Patrick; Lendl, Bernhard; Loza-Alvarez, Pablo; Lyng, Fiona M.; Machill, Susanne; Malherbe, Cedric; Marro, Monica; Marques, Maria Paula M.; Matuszyk, Ewelina; Morasso, Carlo Francesco; Moreau, Myriam; Muhamadali, Howbeer; Mussi, Valentina; Notingher, Ioan; Pacia, Marta Z.; Pavone, Francesco S.; Penel, Guillaume; Petersen, Dennis; Piot, Olivier; Rau, Julietta V.; Richter, Marc; Rybarczyk, Maria Krystyna; Salehi, Hamideh; Schenke-Layland, Katja; Schluecker, Sebastian; Schosserer, Markus; Schuetze, Karin; Sergo, Valter; Sinjab, Faris; Smulko, Janusz; Sockalingum, Ganesh D.; Stiebing, Clara; Stone, Nick; Untereiner, Valerie; Vanna, Renzo; Wieland, Karin; Popp, Juergen; Bocklitz, ThomasAnalytical Chemistry (Washington, DC, United States) (2020), 92 (24), 15745-15756CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)The variable configuration of Raman spectroscopic platforms is one of the major obstacles in establishing Raman spectroscopy as a valuable physicochem. method within real-world scenarios such as clin. diagnostics. For such real world applications like diagnostic classification, the models should ideally be usable to predict data from different setups. Whether it is done by training a rugged model with data from many setups or by a primary-replica strategy where models are developed on a 'primary' setup and the test data are generated on 'replicate' setups, this is only possible if the Raman spectra from different setups are consistent, reproducible, and comparable. However, Raman spectra can be highly sensitive to the measurement conditions, and they change from setup to setup even if the same samples are measured. Although increasingly recognized as an issue, the dependence of the Raman spectra on the instrumental configuration is far from being fully understood and great effort is needed to address the resulting spectral variations and to correct for them. To make the severity of the situation clear, we present a round robin expt. investigating the comparability of 35 Raman spectroscopic devices with different configurations in 15 institutes within seven European countries from the COST (European Cooperation in Science and Technol.) action Raman4clinics. The expt. was developed in a fashion that allows various instrumental configurations ranging from highly confocal setups to fiber-optic based systems with different excitation wavelengths. We illustrate the spectral variations caused by the instrumental configurations from the perspectives of peak shifts, intensity variations, peak widths, and noise levels. We conclude this contribution with recommendations that may help to improve the inter-lab. studies.
- 389Jiang, X.; Yang, M.; Meng, Y.; Jiang, W.; Zhan, J. Cysteamine-Modified Silver Nanoparticle Aggregates for Quantitative SERS Sensing of Pentachlorophenol with a Portable Raman Spectrometer. ACS Appl. Mater. Interfaces 2013, 5, 6902– 6908, DOI: 10.1021/am401718p389Cysteamine-Modified Silver Nanoparticle Aggregates for Quantitative SERS Sensing of Pentachlorophenol with a Portable Raman SpectrometerJiang, Xiaohong; Yang, Min; Meng, Yanjing; Jiang, Wei; Zhan, JinhuaACS Applied Materials & Interfaces (2013), 5 (15), 6902-6908CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Cysteamine-modified silver nanoparticle aggregates has been fabricated for pentachlorophenol (PCP) sensing by surface-enhanced Raman spectroscopy (SERS) using a portable Raman spectrometer. The cysteamine monolayers could preconc. PCP close to the substrate surface through the electrostatic interaction, which makes the SERS detection of PCP possible. Moreover, the Raman bands of cysteamine could be used as the internal spectral ref. in the quant. anal. Qual. detection of PCP was carried out by SERS without any sample pretreatment. Quant. anal. of PCP was further realized based on the prepd. substrate, as the log-log plot of normalized SERS intensity of PCP vs. its concns. exhibits a good linear relationship. The SERS signals collected on 20 randomly selected points show that the relative std. deviation of the normalized Raman intensity is 5.8%, which indicates the substrate had good uniformity. The PCP sensor also shows good long-term stability in the analyte soln. The substrate was cyclic immersed into PCP and methanol soln.; after several cycles, the sensor still had good adsorption to PCP, which revealed the sensor has good reusability. Coupling with a portable Raman spectrometer, the cysteamine-modified silver nanoparticle aggregates have the potential to be used for in situ and routine SERS anal. of PCP in environmental samples.
- 390Lorenz, B.; Guo, S.; Raab, C.; Leisching, P.; Bocklitz, T.; Rösch, P.; Popp, J. Comparison of conventional and shifted excitation Raman difference spectroscopy for bacterial identification. J. Raman Spectrosc. 2022, 53, 1285– 1292, DOI: 10.1002/jrs.6360There is no corresponding record for this reference.
- 391Kazemzadeh, M.; Martinez-Calderon, M.; Xu, W.; Chamley, L. W.; Hisey, C. L.; Broderick, N. G. R. Cascaded Deep Convolutional Neural Networks as Improved Methods of Preprocessing Raman Spectroscopy Data. Anal. Chem. 2022, 94, 12907– 12918, DOI: 10.1021/acs.analchem.2c03082391Cascaded Deep Convolutional Neural Networks as Improved Methods of Preprocessing Raman Spectroscopy DataKazemzadeh, Mohammadrahim; Martinez-Calderon, Miguel; Xu, Weiliang; Chamley, Lawrence W.; Hisey, Colin L.; Broderick, Neil G. R.Analytical Chemistry (Washington, DC, United States) (2022), 94 (37), 12907-12918CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Machine learning has had a significant impact on the value of spectroscopic characterization tools, particularly in biomedical applications, due to its ability to detect latent patterns within complex spectral data. However, it often requires extensive data preprocessing, including baseline correction and denoising, which can lead to an unintentional bias during classification. To address this, we developed two deep learning methods capable of fully preprocessing raw Raman spectroscopy data without any human input. First, cascaded deep convolutional neural networks (CNN) based on either ResNet or U-Net architectures were trained on randomly generated spectra with augmented defects. Then, they were tested using simulated Raman spectra, surface-enhanced Raman spectroscopy (SERS) imaging of chem. species, low resoln. Raman spectra of human bladder cancer tissue, and finally, classification of SERS spectra from human placental extracellular vesicles (EVs). Both approaches resulted in faster training and complete spectral preprocessing in a single step, with more speed, defect tolerance, and classification accuracy compared to conventional methods. These findings indicate that cascaded CNN preprocessing is ideal for biomedical Raman spectroscopy applications in which large nos. of heterogeneous spectra with diverse defects need to be automatically, rapidly, and reproducibly preprocessed.
- 392Cerjan, B.; Yang, X.; Nordlander, P.; Halas, N. J. Asymmetric Aluminum Antennas for Self-Calibrating Surface-Enhanced Infrared Absorption Spectroscopy. ACS Photonics 2016, 3, 354– 360, DOI: 10.1021/acsphotonics.6b00024392Asymmetric Aluminum Antennas for Self-Calibrating Surface-Enhanced Infrared Absorption SpectroscopyCerjan, Benjamin; Yang, Xiao; Nordlander, Peter; Halas, Naomi J.ACS Photonics (2016), 3 (3), 354-360CODEN: APCHD5; ISSN:2330-4022. (American Chemical Society)While there was a tremendous increase of recent interest in noble metal-based antennas as substrates for surface-enhanced IR absorption spectroscopy, more abundant and manufacturable metals may offer similar or addnl. opportunities for this mid-IR sensing modality. The feasibility of Al antennas for SEIRA was examd., by designing and fabricating asym. Al cross antennas with nm-scale gaps. The asym. cross design enables the simultaneous detection of multiple IR vibrational resonances over a broad region of the mid-IR spectrum. The presence of the Al2O3 amorphous surface oxide layer passivates the metal antenna structures and enables a straightforward covalent binding chem. for analyte mols. to the antenna through multiple approaches, in this case using carboxylic acid functional groups. The Al-O stretching mode of the oxide can be used as a self-calibration std. to quantify the no. of analyte mols. on the antenna surface.
- 393Wang, Z.; Zhang, M.; Harrington, P. d. B. Comparison of Three Algorithms for the Baseline Correction of Hyphenated Data Objects. Anal. Chem. 2014, 86, 9050– 9057, DOI: 10.1021/ac501658k393Comparison of Three Algorithms for the Baseline Correction of Hyphenated Data ObjectsWang, Zhengfang; Zhang, Mengliang; Harrington, Peter de B.Analytical Chemistry (Washington, DC, United States) (2014), 86 (18), 9050-9057CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Three novel two-way baseline correction algorithms, i.e., orthogonal basis (OB), fuzzy optimal associative memory (FOAM), and polynomial fitting (PF), were evaluated with HPLC-mass spectrometry (HPLC-MS) and gas chromatog./mass spectrometry (GC/MS) data objects. Among these algorithms, both OB and FOAM are two-way baseline correction algorithms, which reconstruct the entire two-way backgrounds from blank data objects, while the PF algorithm is a pseudo-two-way method, which models each ion chromatogram baseline with a third-order polynomial. The performance of baseline correction methods was first evaluated with respect to the signal-to-noise ratios (SNRs) of 4 major peaks of the HPLC-MS total ion current (TIC) chromatograms of celery seed exts. Then, the effect of baseline correction on pattern recognition was evaluated by using 42 two-way headspace (HS) solid phase microextn. (SPME) GC/MS data objects of 7 polychlorinated biphenyl (PCB) mixt. std. solns. Two types of classifiers, i.e., a fuzzy rule-building expert system (FuRES) and partial least-squares-discriminant anal. (PLS-DA) were evaluated in parallel. Bootstrapped Latin partitions (BLPs) were used to give an unbiased and generalized evaluation of the classification accuracy. SNRs of major peaks of the TIC chromatogram representative of two-way HPLC-MS data objects are increased by baseline correction. In addn., higher prediction accuracies can be obtained by performing baseline correction on the entire GC/MS data set prior to pattern recognition. Also proper data transformation is able to improve the performance of baseline correction. This report is the first of two-way baseline correction methods for hyphenated chromatog./mass spectrometry data objects. Both the orthogonal basis and FOAM baseline correction methods are novel inhouse algorithms and are generally effective for two-way baseline correction. Polynomial fitting is a conventional baseline correction method for one-way data objects and is applied to two-way data objects for the first time. It is applicable when blank data objects are unavailable.
- 394Wolf, S.; Domes, R.; Merian, A.; Domes, C.; Frosch, T. Parallelized Raman Difference Spectroscopy for the Investigation of Chemical Interactions. Anal. Chem. 2022, 94, 10346– 10354, DOI: 10.1021/acs.analchem.2c00222394Parallelized Raman Difference Spectroscopy for the Investigation of Chemical InteractionsWolf, Sebastian; Domes, Robert; Merian, Andreas; Domes, Christian; Frosch, TorstenAnalytical Chemistry (Washington, DC, United States) (2022), 94 (29), 10346-10354CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Raman spectroscopy provides an extremely high chem. selectivity. Raman difference spectroscopy is a technique to reveal even the smallest differences that occur due to weak interactions between substances and changes in the mol. structure. To enable parallelized and highly sensitive Raman difference spectroscopy in a microtiter-array, a diffractive optical element, a lens array, and a fiber bundle were integrated into a Raman spectroscopy setup in a unique fashion. The setup was evaluated with a microtiter-array contg. pyridine-water complexes, and subwavenumber changes below the spectrometer's resoln. could be resolved. The spectral changes were emphasized with two-dimensional correlation anal. D. functional theory calcn. and "atoms in mol." anal. were performed to simulate the intermol. long-range interactions between water and pyridine mols. and to get insight into the involved noncovalent interactions, resp. It was found that by the addn. of pyridine, the energy portion of hydrogen bonds to the total complexation energy between pyridine and water reduces. These results demonstrate the unique abilities of the new setup to investigate subtle changes due to biochem. important mol. interactions and opens new avenues to perform drug binding assays and to monitor highly parallelized chem. reactions.
- 395Heraud, P.; Wood, B. R.; Beardall, J.; McNaughton, D. Effects of pre-processing of Raman spectra on in vivo classification of nutrient status of microalgal cells. Journal of Chemometrics 2006, 20, 193– 197, DOI: 10.1002/cem.990395Effects of pre-processing of Raman spectra on in vivo classification of nutrient status of microalgal cellsHeraud, Philip; Wood, Bayden R.; Beardall, John; McNaughton, DonJournal of Chemometrics (2007), 20 (5), 193-197CODEN: JOCHEU; ISSN:0886-9383. (John Wiley & Sons Ltd.)Raman spectra were obtained from cells of the chlorophyte unicellular eukaryotic alga Dunaliella tertiolecta, which had been grown either under nutrient-replete conditions or starved of nitrogen for 4 days. Spectra were rich in bands which could all be attributed to either chlorophyll a or β-carotene. A cursory examn. of the differences between the spectra of replete and starved cells indicated a decline in chlorophyll α and an increase in β-carotene in chlorophytes. Unprocessed spectra showed pronounced baseline effects. A variety of pre-processing techniques were used in an attempt to visualize the spectral, and hence chem., differences in the transformed data and perform classification based upon these differences. Six types of spectral pre-processing were compared: baseline correction with vector normalization; Multiplicative Scatter Correction (MSC), Extended Multiplicative Signal Correction (EMSC); Std. Normal Variate (SNV); and vector normalized 1st and 2nd deriv. spectra. Results for Soft Independent Modeling of Class Analogy (SIMCA) and Partial Least Squares (PLS) discriminant anal. were compared. All pre-processing methods allowed spectral differences between N-replete and N-starved spectra to be visualized, with derivs. and EMSC scoring the lowest RMSEC and RMSEV values with PLS and also the best overall classification results. SIMCA was not suited to classifying the nutrient classes under any of the pre-treatments, due to the small model distances involved.
- 396Nguyen, C. Q.; Thrift, W. J.; Bhattacharjee, A.; Ranjbar, S.; Gallagher, T.; Darvishzadeh-Varcheie, M.; Sanderson, R. N.; Capolino, F.; Whiteson, K.; Baldi, P.; Hochbaum, A. I.; Ragan, R. Longitudinal Monitoring of Biofilm Formation via Robust Surface-Enhanced Raman Scattering Quantification of Pseudomonas aeruginosa-Produced Metabolites. ACS Appl. Mater. Interfaces 2018, 10, 12364– 12373, DOI: 10.1021/acsami.7b18592396Longitudinal Monitoring of Biofilm Formation via Robust Surface-Enhanced Raman Scattering Quantification of Pseudomonas aeruginosa-Produced MetabolitesNguyen, Cuong Quoc; Thrift, William John; Bhattacharjee, Arunima; Ranjbar, Saba; Gallagher, Tara; Darvishzadeh-Varcheie, Mahsa; Sanderson, Robert Noboru; Capolino, Filippo; Whiteson, Katrine; Baldi, Pierre; Hochbaum, Allon I.; Ragan, ReginaACS Applied Materials & Interfaces (2018), 10 (15), 12364-12373CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Detection of bacterial metabolites at low concns. in fluids with complex background allows for applications ranging from detecting biomarkers of respiratory infections to identifying contaminated medical instruments. Surface-enhanced Raman scattering (SERS) spectroscopy, when utilizing plasmonic nanogaps, has the relatively unique capacity to reach trace mol. detection limits in a label-free format, yet large-area device fabrication incorporating nanogaps with this level of performance has proven difficult. Here, the authors demonstrate the advantages of using chem. assembly to fabricate SERS surfaces with controlled nanometer gap spacings between plasmonic nanospheres. Control of nanogap spacings via the length of the chem. crosslinker provides uniform SERS signals, exhibiting detection of pyocyanin, a secondary metabolite of Pseudomonas aeruginosa, in aq. media at concn. of 100 pg·mL-1. When using machine learning algorithms to analyze the SERS data of the conditioned medium from a bacterial culture, having a more complex background, the authors achieve 1 ng·mL-1 limit of detection of pyocyanin and robust quantification of concn. spanning 5 orders of magnitude. Nanogaps are also incorporated in an in-line microfluidic device, enabling longitudinal monitoring of P. aeruginosa biofilm formation via rapid pyocyanin detection in a medium effluent as early as 3 h after inoculation and quantification in under 9 h. Surface-attached bacteria exposed to a bactericidal antibiotic were differentially less susceptible after 10 h of growth, indicating that these devices may be useful for early intervention of bacterial infections.
- 397Tang, Y.; Zhuang, Y.; Zhang, S.; Smith, Z. J.; Li, Y.; Mu, X.; Li, M.; He, C.; Zheng, X.; Pan, F.; Gao, T.; Zhang, L. Azo-Enhanced Raman Scattering for Enhancing the Sensitivity and Tuning the Frequency of Molecular Vibrations. ACS Central Science 2021, 7, 768– 780, DOI: 10.1021/acscentsci.1c00117There is no corresponding record for this reference.
- 398Zheng, X.; Yan, X.; Ma, J.; Yao, X.; Zhang, J.; Wang, L. Unidirectional/Bidirectional Electron Transfer at the Au/TiO2 Interface Operando Tracked by SERS Spectra from Au and TiO2. ACS Appl. Mater. Interfaces 2021, 13, 16498– 16506, DOI: 10.1021/acsami.1c02540398Unidirectional/Bidirectional Electron Transfer at the Au/TiO2 Interface Operando Tracked by SERS Spectra from Au and TiO2Zheng, Xinlu; Yan, Xuefeng; Ma, Jiayu; Yao, Xinyun; Zhang, Jinlong; Wang, LingzhiACS Applied Materials & Interfaces (2021), 13 (14), 16498-16506CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Although it is well-known that the size can influence the surface plasmon resonance property of coinage metals and the electronic state of the Mott-Schottky junction formed at the metal/semiconductor interface, insights into how the size can be exploited to optimize the photocatalytic activity and selectivity of metal/semiconductor composites are lacking. Here, we utilize operando SERS spectroscopy to identify the size effect on the electron-transfer dynamics and the direction at the Au/TiO2 interface. This effect was characterized by the photocatalytic redn. sites of p-nitrothiophenol, which were self-tracked with the SERS spectra from Au nanoparticle and inverse-opal structured TiO2, resp. The size-dependent unidirectional/bidirectional transfer of photoinduced electrons at the Au/TiO2 interface was revealed by operando SERS spectroscopy, which enables the rational tuning of the redn. selectivity.
- 399Razzell-Hollis, J.; Thiburce, Q.; Tsoi, W. C.; Kim, J. S. Interfacial Chemical Composition and Molecular Order in Organic Photovoltaic Blend Thin Films Probed by Surface-Enhanced Raman Spectroscopy. ACS Appl. Mater. Interfaces 2016, 8, 31469– 31481, DOI: 10.1021/acsami.6b12124There is no corresponding record for this reference.
- 400Zeng, Y.; Ananth, R.; Dill, T. J.; Rodarte, A.; Rozin, M. J.; Bradshaw, N.; Brown, E. R.; Tao, A. R. Metasurface-Enhanced Raman Spectroscopy (mSERS) for Oriented Molecular Sensing. ACS Appl. Mater. Interfaces 2022, 14, 32598– 32607, DOI: 10.1021/acsami.2c01656400Metasurface-Enhanced Raman Spectroscopy (mSERS) for Oriented Molecular SensingZeng, Yuan; Ananth, Riddhi; Dill, Tyler J.; Rodarte, Andrea; Rozin, Matthew J.; Bradshaw, Nathan; Brown, Eric R.; Tao, Andrea R.ACS Applied Materials & Interfaces (2022), 14 (28), 32598-32607CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Surface-enhanced Raman spectroscopy (SERS) is a widely used sensing technique for ultrasensitivity chem. sensing, biomedical detection, and environmental anal. Because SERS signal is proportional to the fourth power of the local elec. field, several SERS applications have focused on the design of plasmonic nanogaps to take advantage of the extremely strong near-field enhancement that results from plasmonic coupling, but few designs have focused on how SERS detection is affected by mol. orientation within these nanogaps. Here, we demonstrate a nanoparticle-on-metal metasurface designed for near-perfect optical absorption as a platform for Raman detection of highly oriented mol. analytes, including two-dimensional materials and arom. mols. This metasurface platform overcomes challenges in nanoparticle aggregation, which commonly leads to low or fluctuating Raman signals in other colloidal nanoparticle platforms. Our metasurface-enhanced Raman spectroscopy (mSERS) platform is based on a colloidal Langmuir-Schaefer deposition, with up to 32% surface coverage d. of nanogaps across an entire sensor chip. In this work, we perform both simulations of the local elec. field and exptl. characterization of the mSERS signal obtained for oriented mol. layers. We then demonstrate this mSERS platform for the quant. detection of the drinking-water toxin polybrominated di-Ph ether (BDE-15), with a limit of detection of 0.25μM under 530μW excitation. This detection limit is comparable to other SERS-based sensors operating at laser powers over 3 orders of magnitude higher, indicating the promise of our mSERS platform for nondestructive and low-level analyte detection.
- 401Yang, G.; Ivanov, I. N.; Ruther, R. E.; Sacci, R. L.; Subjakova, V.; Hallinan, D. T.; Nanda, J. Electrolyte Solvation Structure at Solid-Liquid Interface Probed by Nanogap Surface-Enhanced Raman Spectroscopy. ACS Nano 2018, 12, 10159– 10170, DOI: 10.1021/acsnano.8b05038401Electrolyte Solvation Structure at Solid-Liquid Interface Probed by Nanogap Surface-Enhanced Raman SpectroscopyYang, Guang; Ivanov, Ilia N.; Ruther, Rose E.; Sacci, Robert L.; Subjakova, Veronika; Hallinan, Daniel T.; Nanda, JagjitACS Nano (2018), 12 (10), 10159-10170CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Understanding the fundamental factors that drive ion solvation structure and transport is key to design high-performance, stable battery electrolytes. Reversible ion solvation and desolvation are crit. to the interfacial charge-transfer process across the solid-liq. interface as well as the resulting stability of the solid electrolyte interphase. Herein, the authors report the study of Li+ salt solvation structure in aprotic soln. in the immediate vicinity (∼20 nm) of the solid electrode-liq. interface using surface-enhanced Raman spectroscopy (SERS) from a Au nanoparticle (Au NP) monolayer. The plasmonic coupling between Au NPs produces strong electromagnetic field enhancement in the gap region, leading to a 5 orders of magnitude increase in Raman intensity for electrolyte components and their mixts. namely, LiPF6, fluoroethylene carbonate, ethylene carbonate, and di-Et carbonate. Further, the authors est. and compare the Li-ion solvation no. derived from SERS, std. Raman spectroscopy, and FTIR spectroscopy expts. to monitor and ascertain the changes in the solvation shell diam. in the confined nanogap region where there is max. enhancement of the elec. field. Findings provide a multimodal spectroscopic approach to gain fundamental insights into the mol. structure of the electrolyte at the solid-liq. interface.
- 402Höller, R. P. M.; Jahn, I. J.; Cialla-May, D.; Chanana, M.; Popp, J.; Fery, A.; Kuttner, C. Biomacromolecular-Assembled Nanoclusters: Key Aspects for Robust Colloidal SERS Sensing. ACS Appl. Mater. Interfaces 2020, 12, 57302– 57313, DOI: 10.1021/acsami.0c16398402Biomacromolecular-Assembled Nanoclusters: Key Aspects for Robust Colloidal SERS SensingHoller Roland P M; Fery Andreas; Kuttner Christian; Jahn Izabella J; Cialla-May Dana; Popp Jurgen; Jahn Izabella J; Cialla-May Dana; Popp Jurgen; Jahn Izabella J; Cialla-May Dana; Popp Jurgen; Chanana Munish; Fery Andreas; Fery Andreas; Kuttner Christian; Kuttner ChristianACS applied materials & interfaces (2020), 12 (51), 57302-57313 ISSN:.Superstructures of gold nanospheres offer augmented surface-enhanced Raman scattering (SERS) activities beyond the limits of their individual building blocks. However, for application as reliable and quantitative colloidal SERS probes, some key aspects need to be considered to combine efficiency and robustness with respect to hotspot excitation, analyte adsorption, signal stability, and colloidal stability. For this purpose, we studied core/satellite superstructures with spherical cores as a simple optically isotropic model system. Superstructures of different core sizes were assembled using bovine serum albumin (BSA), which serves as a non-specific biomacromolecular linker and provides electrosteric stabilization. We show that the "noisy" spectral footprint of the protein coating may serve as an internal standard, which allows accurate monitoring of the adsorption kinetics of analytes. The SERS activity was quantified using 4-mercaptobenzoic acid (MBA) as an aromatic low-molecular-weight model analyte. The molar SERS efficiency was studied by variation of the particle (Au(0)) and analyte concentrations with a limit of detection of 10(-7) M MBA. The practical importance of colloidal stability for robust measurement conditions was demonstrated by comparing the superstructures with their citrate-stabilized or protein-coated building blocks. We explain the theoretical background of hotspot formation by a leader/follower relationship of asymmetric control between the core and the satellites and give practical guidelines for robust colloidal SERS sensing probes.
- 403Jubb, A. M.; Allen, H. C. Vibrational Spectroscopic Characterization of Hematite, Maghemite, and Magnetite Thin Films Produced by Vapor Deposition. ACS Appl. Mater. Interfaces 2010, 2, 2804– 2812, DOI: 10.1021/am1004943403Vibrational Spectroscopic Characterization of Hematite, Maghemite, and Magnetite Thin Films Produced by Vapor DepositionJubb, Aaron M.; Allen, Heather C.ACS Applied Materials & Interfaces (2010), 2 (10), 2804-2812CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Thin films of three iron oxide polymorphs, hematite, maghemite, and magnetite, were produced on KBr substrates using a conventional electron beam deposition technique coupled with thermal annealing. This method allowed for iron oxide thin films free from chem. precursor contaminants. The films were characterized using FTIR spectroscopy, Raman microspectroscopy, and ellipsometry. These spectroscopic techniques allowed for a clear assignment of the phase of the iron oxide polymorph films produced along with an examn. of the degree of crystallinity possessed by the films. The films produced were uniform in phase and exhibited decreasing crystallinity as the thickness increased from 40 to 250 nm.
- 404Nguyen, L. H. B.; Olchowka, J.; Belin, S.; Sanz Camacho, P.; Duttine, M.; Iadecola, A.; Fauth, F.; Carlier, D.; Masquelier, C.; Croguennec, L. Monitoring the Crystal Structure and the Electrochemical Properties of Na3(VO)2(PO4)2F through Fe3+ Substitution. ACS Appl. Mater. Interfaces 2019, 11, 38808– 38818, DOI: 10.1021/acsami.9b14249404Monitoring the Crystal Structure and the Electrochemical Properties of Na3(VO)2(PO4)2F through Fe3+ SubstitutionNguyen, Long H. B.; Olchowka, Jacob; Belin, Stephanie; Sanz Camacho, Paula; Duttine, Mathieu; Iadecola, Antonella; Fauth, Francois; Carlier, Dany; Masquelier, Christian; Croguennec, LaurenceACS Applied Materials & Interfaces (2019), 11 (42), 38808-38818CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)We here present the synthesis of a new material, Na3(VO)Fe(PO4)2F2, by the sol-gel method. Its at. and electronic structural descriptions are detd. by a combination of several diffraction and spectroscopy techniques such as synchrotron X-ray powder diffraction and synchrotron X-ray absorption spectroscopy at V and Fe K edges, 57Fe Mossbauer, and 31P solid-state NMR spectroscopy. The crystal structure of this newly obtained phase is similar to that of Na3(VO)2(PO4)2F, with a random distribution of Fe3+ ions over vanadium sites. Even though Fe3+ and V4+ ions situate on the same crystallog. position, their local environment can be studied sep. using 57Fe Mossbauer and X-ray absorption spectroscopy at Fe and V K edges, resp. The Fe3+ ion resides in a sym. octahedral environment, while the octahedral site of V4+ is greatly distorted due to the presence of the vanadyl bond. No electrochem. activity of the Fe4+/Fe3+ redox couple is detected, at least up to 5 V, whereas the redn. of Fe3+ to Fe2+ has been obsd. at ∼1.5 V vs. Na+/Na through the insertion of 0.5 Na+ into Na3(VO)Fe(PO4)2F2. Comparing to Na3(VO)2(PO4)2F, the electrochem. profile of Na3(VO)Fe(PO4)2F2 in the same cycling condition shows a smaller polarization which could be due to a slight improvement in Na+ diffusion process thanks to the presence of Fe3+ in the framework. Furthermore, the desodiation mechanism occurring upon charging is investigated by operando synchrotron X-ray diffraction and operando synchrotron X-ray absorption at V K edge.
- 405Sanchez, S. R.; Bachilo, S. M.; Kadria-Vili, Y.; Lin, C. W.; Weisman, R. B. n,m)-Specific Absorption Cross Sections of Single-Walled Carbon Nanotubes Measured by Variance Spectroscopy. Nano Lett. 2016, 16, 6903– 6909, DOI: 10.1021/acs.nanolett.6b02819405(n,m)-Specific Absorption Cross Sections of Single-Walled Carbon Nanotubes Measured by Variance SpectroscopySanchez, Stephen R.; Bachilo, Sergei M.; Kadria-Vili, Yara; Lin, Ching-Wei; Weisman, R. BruceNano Letters (2016), 16 (11), 6903-6909CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)A new method based on variance spectroscopy has enabled the detn. of abs. absorption cross sections for the 1st electronic transition of 12 (n,m) structural species of semiconducting single-walled C nanotubes (SWCNTs). Spectrally resolved measurements of fluorescence variance in dil. bulk samples provided particle no. concns. of specific SWCNT species. These values were converted to C concns. and correlated with resonant components in the absorbance spectrum to deduce (n,m)-specific absorption cross sections (absorptivities) for nanotubes ranging in diam. from 0.69 to 1.03 nm. The measured cross sections per atom tend to vary inversely with nanotube diam. and are slightly greater for structures of mod 1 type than for mod 2. Directly measured and extrapolated values are now available to support quant. anal. of SWCNT samples through absorption spectroscopy.
- 406Lee, H. K.; Lee, Y. H.; Zhang, Q.; Phang, I. Y.; Tan, J. M. R.; Cui, Y.; Ling, X. Y. Superhydrophobic Surface-Enhanced Raman Scattering Platform Fabricated by Assembly of Ag Nanocubes for Trace Molecular Sensing. ACS Appl. Mater. Interfaces 2013, 5, 11409– 11418, DOI: 10.1021/am403655g406Superhydrophobic Surface-Enhanced Raman Scattering Platform Fabricated by Assembly of Ag Nanocubes for Trace Molecular SensingLee, Hiang Kwee; Lee, Yih Hong; Zhang, Qi; Phang, In Yee; Tan, Joel Ming Rui; Cui, Yan; Ling, Xing YiACS Applied Materials & Interfaces (2013), 5 (21), 11409-11418CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)An anal. platform suitable for trace detection using a small vol. of analyte is pertinent to the field of toxin detection and criminol. Plasmonic nanostructures provide surface-enhanced Raman scattering (SERS) that can potentially achieve trace toxins and/or mols. detection. However, the detection of highly dild., small vol. samples remains a challenge. Here, the authors fabricate a superhydrophobic SERS platform by assembling Ag nanocubes that support strong surface plasmon and chem. functionalization for trace detection with sample vol. of just 1 μL. The authors' strategy integrates the intense electromagnetic field confinement generated by Ag nanocubes with a superhydrophobic surface capable of analyte concn. to lower the mol. detection limit. Single cryst. Ag nanocubes are assembled using the Langmuir-Blodgett technique to create surface roughness. To create a stable superhydrophobic SERS platform, an addnl. 25 nm Ag coating is evapd. over the Ag nanocubes to 'weld' the Ag nanocubes onto the substrate followed by chem. functionalization with perfluorodecanethiol. The resulting substrate has an advancing contact angle of 169° ± 5°. The authors' superhydrophobic platform confines analyte mols. within a small area and prevents the random spreading of mols. An analyte concg. factor of 14-fold is attained, as compared to a hydrophilic surface. Consequently, the detection limit of the authors' superhydrophobic SERS substrate reaches 10-16 M (100 aM) for rhodamine 6G using 1 μL analyte solns. An anal. SERS enhancement factor of 1011 is achieved. The authors' protocol is a general method that provides a simple, cost-effective approach to develop a stable and uniform superhydrophobic SERS platform for trace mol. sensing.
- 407Hahm, E.; Cha, M. G.; Kang, E. J.; Pham, X. H.; Lee, S. H.; Kim, H. M.; Kim, D. E.; Lee, Y. S.; Jeong, D. H.; Jun, B. H. Multilayer Ag-Embedded Silica Nanostructure as a Surface-Enhanced Raman Scattering-Based Chemical Sensor with Dual-Function Internal Standards. ACS Appl. Mater. Interfaces 2018, 10, 40748– 40755, DOI: 10.1021/acsami.8b12640407Multilayer Ag-Embedded Silica Nanostructure as a Surface-Enhanced Raman Scattering-Based Chemical Sensor with Dual-Function Internal StandardsHahm, Eunil; Cha, Myeong Geun; Kang, Eun Ji; Pham, Xuan-Hung; Lee, Sang Hun; Kim, Hyung-Mo; Kim, Dong-Eun; Lee, Yoon-Sik; Jeong, Dae-Hong; Jun, Bong-HyunACS Applied Materials & Interfaces (2018), 10 (47), 40748-40755CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Surface-enhanced Raman scattering (SERS) spectroscopy is attractive in various detection anal. fields. However, the quant. method using SERS spectroscopy remains as an area to be developed. The key issues in developing quant. anal. methods by using SERS spectroscopy are the fabrication of reliable SERS-active materials such as nanoparticle-based structures and the acquisition of the SERS signal without any disturbance that may change the SERS signal intensity and frequency. Here, the fabrication of seamless multilayered core-shell nanoparticles with an embedded Raman label compd. as an internal std. (MLRLC dots) for quant. SERS anal. is reported. The embedded Raman label compd. in the nanostructure provides a ref. value for calibrating the SERS signals. By using the MLRLC dots, it is possible to gain target analyte signals of different concns. while retaining the Raman signal of the internal std. The ML4-BBT dots, contg. 4-bromobenzenethiol (4-BBT) as an internal std., are successfully applied in the quant. anal. of 4-fluorobenzenethiol and thiram, a model pesticide. Addnl., ratiometric anal. was proved practical through normalization of the relative SERS intensity. The ratiometric strategy could be applied to various SERS substrates for quant. detection of a wide variety of targets.
- 408Feng, H.; Fu, Q.; Du, W.; Zhu, R.; Ge, X.; Wang, C.; Li, Q.; Su, L.; Yang, H.; Song, J. Quantitative Assessment of Copper(II) in Wilson’s Disease Based on Photoacoustic Imaging and Ratiometric Surface-Enhanced Raman Scattering. ACS Nano 2021, 15, 3402– 3414, DOI: 10.1021/acsnano.0c10407408Quantitative Assessment of Copper(II) in Wilson's Disease Based on Photoacoustic Imaging and Ratiometric Surface-Enhanced Raman ScatteringFeng, Hongjuan; Fu, Qinrui; Du, Wei; Zhu, Rong; Ge, Xiaoguang; Wang, Chenlu; Li, Qingqing; Su, Lichao; Yang, Huanghao; Song, JibinACS Nano (2021), 15 (2), 3402-3414CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Cu2+ is closely related to the occurrence and development of Wilson's disease (WD), and quant. detection of various copper indicators (esp. liver Cu2 and urinary Cu2+) is the key step for the early diagnosis of WD in the clinic. However, the clinic Cu2+ detection approach was mainly based on testing the liver tissue through combined invasive liver biopsy and the ICP-MS method, which is painful for the patient and limited in detg. WD status in real-time. Herein, we rationally designed a type of Cu2+-activated nanoprobe based on nanogapped gold nanoparticles (AuNNP) and poly(N-isopropylacrylamide) (PNIPAM) to simultaneously quantify the liver Cu2+ content and urinary Cu2+ in WD by photoacoustic (PA) imaging and ratiometric surface-enhanced Raman scattering (SERS), resp. In the nanoprobe, one Raman mol. of 2-naphthylthiol (NAT) was placed in the nanogap of AuNNP. PNIPAM and the other Raman mol. mercaptobenzonitrile (MBN) were coated on the AuNNP surface, named AuNNP-NAT@MBN/PNIPAM. Cu2+ can efficiently coordinate with the chelator PNIPAM and lead to aggregation of the nanoprobe, resulting in the absorption red-shift and increased PA performance of the nanoprobe in the NIR-II window. Meanwhile, the SERS signal at 2223 cm-1 of MBN is amplified, while the SERS signal at 1378 cm-1 of NAT remains stable, generating a ratiometric SERS I2223/I1378 signal. Both NIR-II PA1250 nm and SERS I2223/I1378 signals of the nanoprobe show a linear relationship with the concn. of Cu2+. The nanoprobe was successfully applied for in vivo quant. detection of liver Cu2+ of WD mice through NIR-II PA imaging and accurate quantification of urinary Cu2+ of WD patients by ratiometric SERS. We anticipate that the activatable nanoprobe might be applied for assisting an early, precise diagnosis of WD in the clinic in the future.
- 409Subaihi, A.; Muhamadali, H.; Mutter, S. T.; Blanch, E.; Ellis, D. I.; Goodacre, R. Quantitative detection of codeine in human plasma using surface-enhanced Raman scattering via adaptation of the isotopic labelling principle. Analyst 2017, 142, 1099– 1105, DOI: 10.1039/C7AN00193BThere is no corresponding record for this reference.
- 410Fu, X.; Lou, T.; Chen, Z.; Lin, M.; Feng, W.; Chen, L. ″Turn-on″ fluorescence detection of lead ions based on accelerated leaching of gold nanoparticles on the surface of graphene. ACS Appl. Mater. Interfaces 2012, 4, 1080– 1086, DOI: 10.1021/am201711j410"Turn-on" Fluorescence Detection of Lead Ions Based on Accelerated Leaching of Gold Nanoparticles on the Surface of GrapheneFu, Xiuli; Lou, Tingting; Chen, Zhaopeng; Lin, Meng; Feng, Weiwei; Chen, LingxinACS Applied Materials & Interfaces (2012), 4 (2), 1080-1086CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)A novel platform for effective turn-on fluorescence sensing of lead ions (Pb2+) in aq. soln. was developed based on gold nanoparticle (AuNP)-functionalized graphene. The AuNP-functionalized graphene exhibited minimal background fluorescence because of the extraordinarily high quenching ability of AuNPs. The AuNP-functionalized graphene underwent fluorescence restoration as well as significant enhancement upon adding Pb2+, which was attributed to the fact that Pb2+ could accelerate the leaching rate of the AuNPs on graphene surfaces in the presence of both thiosulfate (S2O32-) and 2-mercaptoethanol (2-ME). Consequently, this could be used as the basis for selective detection of Pb2+. With the optimum conditions chosen, the relative fluorescence intensity showed good linearity vs. logarithm concn. of Pb2+ at 50-1000 nM (R = 0.9982), and a detection limit of 10 nM. High selectivity over common coexistent metal ions was also demonstrated. The practical application had been carried out for detn. of Pb2+ in tap water and mineral water samples. The Pb2+-specific turn-on fluorescence sensor, based on Pb2+ accelerated leaching of AuNPs on the surface of graphene, provided new opportunities for highly sensitive and selective Pb2+ detection in aq. media.
- 411Ci, Q.; Liu, J.; Qin, X.; Han, L.; Li, H.; Yu, H.; Lim, K. L.; Zhang, C. W.; Li, L.; Huang, W. Polydopamine Dots-Based Fluorescent Nanoswitch Assay for Reversible Recognition of Glutamic Acid and Al3+ in Human Serum and Living Cell. ACS Appl. Mater. Interfaces 2018, 10, 35760– 35769, DOI: 10.1021/acsami.8b12087411Polydopamine Dots-Based Fluorescent Nanoswitch Assay for Reversible Recognition of Glutamic Acid and Al3+ in Human Serum and Living CellCi, Qiaoqiao; Liu, Jinhua; Qin, Xiaofei; Han, Linqi; Li, Hai; Yu, Haidong; Lim, Kah-Leong; Zhang, Cheng-Wu; Li, Lin; Huang, WeiACS Applied Materials & Interfaces (2018), 10 (42), 35760-35769CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)We developed a facile and feasible fluorescent nanoswitch assay for reversible recognition of glutamate (Glu) and Al3+ in human serum and living cell. The proposed nanoswitch assay is based on our recently developed method for controlled synthesis of fluorescent polydopamine dots (PDADs) at room temp. with dopamine as the sole precursor. The fluorescence of nanoswitch assay could be quickly and efficiently quenched by Glu (turn-Off), and the addn. of Al3+ could recover the fluorescence of the PDADs-Glu system (turn-On). Meanwhile, the reversible recognition of Glu and Al3+ in this nanoswitch system was stable after three cycles. Addnl., the system displayed excellent performance for Glu and Al3+ detn. with a low detection limit of 0.12 and 0.2 μM, resp. Moreover, PDADs are successfully applied to det. Glu and monitor Al3+ in human serum. Noteworthy, the nanoswitch assay is transported into HepG2 cells and realized "Off" detection of Glu and "On" sensing Al3+ in the living cells. Therefore, this PDADs-based nanoswitch assay provides a strategy to develop reversible recognition biosensors for intracellular and external mol. anal.
- 412Hidi, I. J.; Jahn, M.; Weber, K.; Bocklitz, T.; Pletz, M. W.; Cialla-May, D.; Popp, J. Lab-on-a-Chip-Surface Enhanced Raman Scattering Combined with the Standard Addition Method: Toward the Quantification of Nitroxoline in Spiked Human Urine Samples. Anal. Chem. 2016, 88, 9173– 9180, DOI: 10.1021/acs.analchem.6b02316412Lab-on-a-Chip-Surface Enhanced Raman Scattering Combined with the Standard Addition Method: Toward the Quantification of Nitroxoline in Spiked Human Urine SamplesHidi, Izabella J.; Jahn, Martin; Weber, Karina; Bocklitz, Thomas; Pletz, Mathias W.; Cialla-May, Dana; Popp, JuergenAnalytical Chemistry (Washington, DC, United States) (2016), 88 (18), 9173-9180CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)The emergence of antibacterial resistance and the development of new drugs lead to a continuous change of guidelines for medical treatments. Hence, new anal. tools are required for the detection of drugs in biol. fluids. In this study, the first surface enhanced Raman scattering (SERS) detection of nitroxoline (NTX) in purified water and in spiked human urine samples is reported. Insights concerning the nature of the mol.-metal interaction and its influence on the overall SERS signal are provided. Furthermore, three randomly collected urine samples originating from a healthy volunteer were spiked to assess the limit of detection (LOD), the limit of quantification (LOQ), and the linear dynamic range of the lab-on-a-chip SERS (LoC-SERS) method for NTX detection in human urine. The LOD is ∼3 μM (0.57 mg/L), LOQ ∼ 6.5 μM (1.23 mg/L) while the linear range is between 4.28 and 42.8 μM (0.81-8.13 mg/L). This covers the min. inhibitory concn. (MIC) values of the most commonly encountered uropathogens. Finally, seven clin. samples having an "unknown" NTX concn. were simulated. The LoC-SERS technique combined with the std. addn. method and statistical data anal. provided a good prediction of the unknown concns. Addnl., it is also demonstrated that the predictions carried out by multicurve resoln. alternating least-squares (MCR-ALS) algorithm provides reliable results, and it is preferred to a univariate statistical approach.
- 413Qing, G.; Lu, Q.; Li, X.; Liu, J.; Ye, M.; Liang, X.; Sun, T. Hydrogen bond based smart polymer for highly selective and tunable capture of multiply phosphorylated peptides. Nat. Commun. 2017, 8, 461, DOI: 10.1038/s41467-017-00464-0413Hydrogen bond based smart polymer for highly selective and tunable capture of multiply phosphorylated peptidesQing Guangyan; Lu Qi; Sun Taolei; Li Xiuling; Liu Jing; Ye Mingliang; Liang Xinmiao; Sun TaoleiNature communications (2017), 8 (1), 461 ISSN:.Multisite phosphorylation is an important and common mechanism for finely regulating protein functions and subsequent cellular responses. However, this study is largely restricted by the difficulty to capture low-abundance multiply phosphorylated peptides (MPPs) from complex biosamples owing to the limitation of enrichment materials and their interactions with phosphates. Here we show that smart polymer can serve as an ideal platform to resolve this challenge. Driven by specific but tunable hydrogen bonding interactions, the smart polymer displays differential complexation with MPPs, singly phosphorylated and non-modified peptides. Importantly, MPP binding can be modulated conveniently and precisely by solution conditions, resulting in highly controllable MPP adsorption on material surface. This facilitates excellent performance in MPP enrichment and separation from model proteins and real biosamples. High enrichment selectivity and coverage, extraordinary adsorption capacities and recovery towards MPPs, as well as high discovery rates of unique phosphorylation sites, suggest its great potential in phosphoproteomics studies.Capture of low-abundance multiply phosphorylated peptides (MPPs) is difficult due to limitation of enrichment materials and their interactions with phosphates. Here the authors show, a smart polymer driven by specific but tunable hydrogen bonding interactions can differentially complex with MPPs, singly phosphorylated and non-modified peptides.
- 414Jordan, M. I.; Mitchell, T. M. Machine learning: Trends, perspectives, and prospects. Science 2015, 349, 255– 260, DOI: 10.1126/science.aaa8415414Machine learning: Trends, perspectives, and prospectsJordan, M. I.; Mitchell, T. M.Science (Washington, DC, United States) (2015), 349 (6245), 255-260CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)Machine learning addresses the question of how to build computers that improve automatically through experience. It is one of today's most rapidly growing tech. fields, lying at the intersection of computer science and statistics, and at the core of artificial intelligence and data science. Recent progress in machine learning has been driven both by the development of new learning algorithms and theory and by the ongoing explosion in the availability of online data and low-cost computation. The adoption of data-intensive machine-learning methods can be found throughout science, technol. and commerce, leading to more evidence-based decision-making across many walks of life, including health care, manufg., education, financial modeling, policing, and marketing.
- 415Leong, Y. X.; Tan, E. X.; Leong, S. X.; Lin Koh, C. S.; Thanh Nguyen, L. B.; Ting Chen, J. R.; Xia, K.; Ling, X. Y. Where Nanosensors Meet Machine Learning: Prospects and Challenges in Detecting Disease X. ACS Nano 2022, 16, 13279– 13293, DOI: 10.1021/acsnano.2c05731415Where Nanosensors Meet Machine Learning: Prospects and Challenges in Detecting Disease XLeong, Yong Xiang; Tan, Emily Xi; Leong, Shi Xuan; Lin Koh, Charlynn Sher; Thanh Nguyen, Lam Bang; Ting Chen, Jaslyn Ru; Xia, Kelin; Ling, Xing YiACS Nano (2022), 16 (9), 13279-13293CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Disease X is a hypothetical unknown disease that has the potential to cause an epidemic or pandemic outbreak in the future. Nanosensors are attractive portable devices that can swiftly screen disease biomarkers on site, reducing the reliance on lab.-based analyses. However, conventional data analytics limit the progress of nanosensor research. In this Perspective, we highlight the integral role of machine learning (ML) algorithms in advancing nanosensing strategies toward Disease X detection. We first summarize recent progress in utilizing ML algorithms for the smart design and fabrication of custom nanosensor platforms as well as realizing rapid on-site prediction of infection statuses. Subsequently, we discuss promising prospects in further harnessing the potential of ML algorithms in other aspects of nanosensor development and biomarker detection.
- 416Chen, A.; Wang, Z.; Zhang, X.; Chen, L.; Hu, X.; Han, Y.; Cai, J.; Zhou, Z.; Li, J. Accelerated Mining of 2D Van der Waals Heterojunctions by Integrating Supervised and Unsupervised Learning. Chem. Mater. 2022, 34, 5571– 5583, DOI: 10.1021/acs.chemmater.2c00641416Accelerated Mining of 2D Van der Waals Heterojunctions by Integrating Supervised and Unsupervised LearningChen, An; Wang, Zhilong; Zhang, Xu; Chen, Letian; Hu, Xu; Han, Yanqiang; Cai, Junfei; Zhou, Zhen; Li, JinjinChemistry of Materials (2022), 34 (12), 5571-5583CODEN: CMATEX; ISSN:0897-4756. (American Chemical Society)The contact resistance of the metal-semiconductor interface at the source and drain increases as the injection of carriers decreases, degrading the device performance. Reducing the Schottky barrier height (SBH) at the metal-semiconductor interface is an effective way of reducing the contact resistance. Therefore, exploring Ohmic contact (no Schottky barrier) or low contact resistance two-dimensional (2D) semiconductor/metal heterojunctions is crit. for developing high-performance electronic devices. We generate a comprehensive dataset from the periodic table consisting of 1092 potential 2D semiconductor/metal heterojunctions with good contact performances and demonstrate that the small interfacial dipole and the elimination of localized surface states are essential for designing advanced 2D metal-semiconductor systems with small SBHs. We use integrated supervised and unsupervised learning, as well as first-principles calcns., to screen 6 potential 2D van der Waals metal-semiconductor heterojunctions (BTe-NbSe2, Al2SO-Zn3C2, iAl2SO-Zn3C2, GaSe-NbS2, GaSe-NbSe2, and GeSe-VS2) with Ohmic contact and high tunneling probabilities from 1092 candidates. The proposed method takes less than 5 s to execute and is far superior to traditional first-principles calcns. in both time and cost, demonstrating the superiority of using machine learning for screening materials and that unsupervised assisted algorithm can alleviate the problem of data scarcity to predict the behaviors of complex dynamical systems.
- 417Anker, A. S.; Butler, K. T.; Selvan, R.; Jensen, K. M. Ø. Machine learning for analysis of experimental scattering and spectroscopy data in materials chemistry. Chemical Science 2023, 14, 14003– 14019, DOI: 10.1039/D3SC05081EThere is no corresponding record for this reference.
- 418Glielmo, A.; Husic, B. E.; Rodriguez, A.; Clementi, C.; Noé, F.; Laio, A. Unsupervised Learning Methods for Molecular Simulation Data. Chem. Rev. 2021, 121, 9722– 9758, DOI: 10.1021/acs.chemrev.0c01195418Unsupervised Learning Methods for Molecular Simulation DataGlielmo, Aldo; Husic, Brooke E.; Rodriguez, Alex; Clementi, Cecilia; Noe, Frank; Laio, AlessandroChemical Reviews (Washington, DC, United States) (2021), 121 (16), 9722-9758CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review. Unsupervised learning is becoming an essential tool to analyze the increasingly large amts. of data produced by atomistic and mol. simulations, in material science, solid state physics, biophysics, and biochem. In this Review, we provide a comprehensive overview of the methods of unsupervised learning that have been most commonly used to investigate simulation data and indicate likely directions for further developments in the field. In particular, we discuss feature representation of mol. systems and present state-of-the-art algorithms of dimensionality redn., d. estn., and clustering, and kinetic models. We divide our discussion into self-contained sections, each discussing a specific method. In each section, we briefly touch upon the math. and algorithmic foundations of the method, highlight its strengths and limitations, and describe the specific ways in which it has been used-or can be used-to analyze mol. simulation data.
- 419Yuan, Y.; Ren, J.; Xue, H.; Li, J.; Tang, F.; La, P.; Lu, X. Insight into the Electronic Properties of Semiconductor Heterostructure Based on Machine Learning and First-Principles. ACS Appl. Mater. Interfaces 2023, 15, 12462– 12472, DOI: 10.1021/acsami.2c15957There is no corresponding record for this reference.
- 420Willhelm, D.; Wilson, N.; Arroyave, R.; Qian, X.; Cagin, T.; Pachter, R.; Qian, X. Predicting Van der Waals Heterostructures by a Combined Machine Learning and Density Functional Theory Approach. ACS Appl. Mater. Interfaces 2022, 14, 25907– 25919, DOI: 10.1021/acsami.2c04403There is no corresponding record for this reference.
- 421Singh, A. V.; Maharjan, R. S.; Kanase, A.; Siewert, K.; Rosenkranz, D.; Singh, R.; Laux, P.; Luch, A. Machine-Learning-Based Approach to Decode the Influence of Nanomaterial Properties on Their Interaction with Cells. ACS Appl. Mater. Interfaces 2021, 13, 1943– 1955, DOI: 10.1021/acsami.0c18470421Machine-Learning-Based Approach to Decode the Influence of Nanomaterial Properties on Their Interaction with CellsSingh, Ajay Vikram; Maharjan, Romi-Singh; Kanase, Anurag; Siewert, Katherina; Rosenkranz, Daniel; Singh, Rishabh; Laux, Peter; Luch, AndreasACS Applied Materials & Interfaces (2021), 13 (1), 1943-1955CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)In an in vitro nanotoxicity system, cell-nanoparticle (NP) interaction leads to the surface adsorption, uptake, and changes into nuclei/cell phenotype and chem., as an indicator of oxidative stress, genotoxicity, and carcinogenicity. Different types of nanomaterials and their chem. compn. or "corona" have been widely studied in context with nanotoxicol. However, rare reports are available, which delineate the details of the cell shape index (CSI) and nuclear area factors (NAFs) as a descriptor of the type of nanomaterials. In this paper, we propose a machine-learning-based graph modeling and correlation-establishing approach using tight junction protein ZO-1-mediated alteration in the cell/nuclei phenotype to quantify and propose it as indexes of cell-NP interactions. We believe that the phenotypic variation (CSI and NAF) in the epithelial cell is governed by the physicochem. descriptors (e.g., shape, size, zeta potential, concn., diffusion coeffs., polydispersity, and so on) of the different classes of nanomaterials, which critically dets. the intracellular uptake or cell membrane interactions when exposed to the epithelial cells at sub-lethal concns. The intrinsic and extrinsic physicochem. properties of the representative nanomaterials (NMs) were measured using optical (dynamic light scattering, NP tracking anal.) methods to create a set of nanodescriptors contributing to cell-NM interactions via phenotype adjustments. We used correlation function as a machine-learning algorithm to successfully predict cell and nuclei shapes and polarity functions as phenotypic markers for five different classes of nanomaterials studied herein this report. The CSI and NAF as nanodescriptors can be used as intuitive cell phenotypic parameters to define the safety of nanomaterials extensively used in consumer products and nanomedicine.
- 422Pan, Z.; Zhou, Y.; Zhang, L. Photoelectrochemical Properties, Machine Learning, and Symbolic Regression for Molecularly Engineered Halide Perovskite Materials in Water. ACS Appl. Mater. Interfaces 2022, 14, 9933– 9943, DOI: 10.1021/acsami.2c00568422Photoelectrochemical Properties, Machine Learning, and Symbolic Regression for Molecularly Engineered Halide Perovskite Materials in WaterPan, Zheng; Zhou, Yinguo; Zhang, LeiACS Applied Materials & Interfaces (2022), 14 (7), 9933-9943CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)The machine learning techniques are capable of predicting virtual material design space and optimizing material fabrication parameters. In this article, we construct machine learning models to describe the photoelectrochem. properties of molecularly engineered halide perovskite materials based on CH3NH3PbI3 in an aq. soln. and predict a complex multidimensional design space for the halide perovskite materials. The machine learning models are trained and tested based on an exptl. photocurrent data set consisting of 360 data points with varying exptl. conditions and dye structures. Machine learning algorithms including support vector machine (SVM), random forest, k-nearest neighbors, Rpart, Xgboost, and Kriging algorithms are compared, with the Kriging algorithm achieving the best accuracies (r = 0.99 and R2 = 0.98) and SVM achieving the second best. A total of 50,905 data points representing the complex multidimensional design space are predicted via the machine-learned models to benefit the future perovskite studies. In addn., the symbolic regression based on the genetic algorithms effectively and automatically designs hybrid descriptors that outperform the individual descriptors. This article highlights the machine learning and symbolic regression methods for designing stable and high-performance halide perovskite materials and serves as a platform for further exptl. optimization of halide perovskite materials.
- 423Shin, H.; Jeong, H.; Park, J.; Hong, S.; Choi, Y. Correlation between Cancerous Exosomes and Protein Markers Based on Surface-Enhanced Raman Spectroscopy (SERS) and Principal Component Analysis (PCA). ACS Sensors 2018, 3, 2637– 2643, DOI: 10.1021/acssensors.8b01047423Correlation between Cancerous Exosomes and Protein Markers Based on Surface-Enhanced Raman Spectroscopy (SERS) and Principal Component Analysis (PCA)Shin, Hyunku; Jeong, Hyesun; Park, Jaena; Hong, Sunghoi; Choi, YeonhoACS Sensors (2018), 3 (12), 2637-2643CODEN: ASCEFJ; ISSN:2379-3694. (American Chemical Society)Exosomes, which are nanovesicles secreted by cells, are promising biomarkers for cancer diagnosis and prognosis, based on their sp. surface protein compns. Here, we demonstrate the correlation of nonsmall cell lung cancer (NSCLC) cell-derived exosomes and potential protein markers by unique Raman scattering profiles and principal component anal. (PCA) for cancer diagnosis. On the basis of surface enhanced Raman scattering (SERS) signals of exosomes from normal and NSCLC cells, we extd. Raman patterns of cancerous exosomes by PCA and clarified specific patterns as unique peaks through quant. anal. with ratiometric mixts. of cancerous and normal exosomes. The unique peaks correlated well with cancerous exosome ratio (R2 > 90%) as the unique Raman band of NSCLC exosome. To examine the origin of the unique peaks, we compared these unique peaks with characteristic Raman bands of several exosomal protein markers (CD9, CD81, EpCAM, and EGFR). EGFR had 1.97-fold similarity in Raman profiles than other markers, and it showed dominant expression against the cancerous exosomes in an immunoblotting result. We expect that these results will contribute to studies on exosomal surface protein markers for diagnosis of cancers.
- 424Ding, Z.; Wang, C.; Song, X.; Li, N.; Zheng, X.; Wang, C.; Su, M.; Liu, H. Strong π-Metal Interaction Enables Liquid Interfacial Nanoarray–Molecule Co-assembly for Raman Sensing of Ultratrace Fentanyl Doped in Heroin, Ketamine, Morphine, and Real Urine. ACS Appl. Mater. Interfaces 2023, 15, 12570– 12579, DOI: 10.1021/acsami.2c22607424Strong π-Metal Interaction Enables Liquid Interfacial Nanoarray-Molecule Co-assembly for Raman Sensing of Ultratrace Fentanyl Doped in Heroin, Ketamine, Morphine, and Real UrineDing, Zhongxiang; Wang, Chao; Song, Xin; Li, Ning; Zheng, Xinyong; Wang, Chenxue; Su, Mengke; Liu, HonglinACS Applied Materials & Interfaces (2023), 15 (9), 12570-12579CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Toward the challenge on reliable detn. of trace fentanyl to avoid opioid overdose death in drug crisis, here we realize rapid and direct detection of trace fentanyl in real human urine without pretreatment by a portable surface enhanced Raman spectroscopy (SERS) strategy on liq./liq. interfacial (LLI) plasmonic arrays. It was obsd. that fentanyl could interact with the gold nanoparticles (GNPs) surface, facilitate the LLI self-assembly, and consequently amplify the detection sensitivity with a limit of detection (LOD) as low as 1 ng/mL in aq. soln. and 50 ng/mL spiked in urine. Furthermore, we achieve multiplex blind sample recognition and classification of ultratrace fentanyl doped in other illegal drugs, which has extremely low LODs at mass concns. of 0.02% (2 ng in 10μg of heroin), 0.02% (2 ng in 10μg of ketamine), and 0.1% (10 ng in 10μg of morphine). A logic circuit of the AND gate was constructed for automatic recognition of illegal drugs with or without fentanyl doping. The data-driven analog soft independent modeling model could quickly distinguish fentanyl-doped samples from illegal drugs with 100% specificity. Mol. dynamics (MD) simulation elucidates the underlying mol. mechanism of nanoarray-mol. co-assembly through strong π-metal interactions and the differences in the SERS signal of various drug mols. It paves a rapid identification, quantification, and classification strategy for trace fentanyl anal., indicating broad application prospects in response to the opioid epidemic crisis.
- 425Leong, Y. X.; Lee, Y. H.; Koh, C. S. L.; Phan-Quang, G. C.; Han, X.; Phang, I. Y.; Ling, X. Y. Surface-Enhanced Raman Scattering (SERS) Taster: A Machine-Learning-Driven Multireceptor Platform for Multiplex Profiling of Wine Flavors. Nano Lett. 2021, 21, 2642– 2649, DOI: 10.1021/acs.nanolett.1c00416425Surface-Enhanced Raman Scattering (SERS) Taster: A Machine-Learning-Driven Multireceptor Platform for Multiplex Profiling of Wine FlavorsLeong, Yong Xiang; Lee, Yih Hong; Koh, Charlynn Sher Lin; Phan-Quang, Gia Chuong; Han, Xuemei; Phang, In Yee; Ling, Xing YiNano Letters (2021), 21 (6), 2642-2649CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)Integrating machine learning with surface-enhanced Raman scattering (SERS) accelerates the development of practical sensing devices. Such integration, in combination with direct detection or indirect analyte capturing strategies, is key to achieving high predictive accuracies even in complex matrixes. However, in-depth understanding of spectral variations arising from specific chem. interactions is essential to prevent model overfit. Herein, we design a machine-learning-driven "SERS taster" to simultaneously harness useful vibrational information from multiple receptors for enhanced multiplex profiling of five wine flavor mols. at parts-per-million levels. Our receptors employ numerous noncovalent interactions to capture chem. functionalities within flavor mols. By strategically combining all receptor-flavor SERS spectra, we construct comprehensive "SERS superprofiles" for predictive analytics using chemometrics. We elucidate crucial mol.-level interactions in flavor identification and further demonstrate the differentiation of primary, secondary, and tertiary alc. functionalities. Our SERS taster also achieves perfect accuracies in multiplex flavor quantification in an artificial wine matrix.
- 426Nguyen, L. B. T.; Leong, Y. X.; Koh, C. S. L.; Leong, S. X.; Boong, S. K.; Sim, H. Y. F.; Phan-Quang, G. C.; Phang, I. Y.; Ling, X. Y. Inducing Ring Complexation for Efficient Capture and Detection of Small Gaseous Molecules Using SERS for Environmental Surveillance. Angew. Chem., Int. Ed. Engl. 2022, 61, e202207447, DOI: 10.1002/anie.202207447There is no corresponding record for this reference.
- 427Lever, J.; Krzywinski, M.; Altman, N. Principal component analysis. Nat Methods 2017, 14, 641– 642, DOI: 10.1038/nmeth.4346427Points of Significance Principal component analysisLever, Jake; Krzywinski, Martin; Altman, NaomiNature Methods (2017), 14 (7), 641-642CODEN: NMAEA3; ISSN:1548-7091. (Nature Publishing Group)PCA helps you interpret your data, but it will not always find the important patterns.
- 428Nicholas, T. C.; Alexandrov, E. V.; Blatov, V. A.; Shevchenko, A. P.; Proserpio, D. M.; Goodwin, A. L.; Deringer, V. L. Visualization and Quantification of Geometric Diversity in Metal–Organic Frameworks. Chem. Mater. 2021, 33, 8289– 8300, DOI: 10.1021/acs.chemmater.1c02439428Visualization and Quantification of Geometric Diversity in Metal-Organic FrameworksNicholas, Thomas C.; Alexandrov, Eugeny V.; Blatov, Vladislav A.; Shevchenko, Alexander P.; Proserpio, Davide M.; Goodwin, Andrew L.; Deringer, Volker L.Chemistry of Materials (2021), 33 (21), 8289-8300CODEN: CMATEX; ISSN:0897-4756. (American Chemical Society)With ever-growing nos. of metal-org. framework (MOF) materials being reported, new computational approaches are required for a quant. understanding of structure-property correlations in MOFs. Here, we show how structural coarse-graining and embedding ("unsupervised learning") schemes can together give new insights into the geometric diversity of MOF structures. Based on a curated data set of 1262 reported exptl. structures, we automatically generate coarse-grained and rescaled representations which we couple to a kernel-based similarity metric and to widely used embedding schemes. This approach allows us to visualize the breadth of geometric diversity within individual topologies and to quantify the distributions of local and global similarities across the structural space of MOFs. The methodol. is implemented in an openly available Python package and is expected to be useful in future high-throughput studies.
- 429Sigle, M.; Rohlfing, A. K.; Kenny, M.; Scheuermann, S.; Sun, N.; Graeßner, U.; Haug, V.; Sudmann, J.; Seitz, C. M.; Heinzmann, D.; Schenke-Layland, K.; Maguire, P. B.; Walch, A.; Marzi, J.; Gawaz, M. P. Translating genomic tools to Raman spectroscopy analysis enables high-dimensional tissue characterization on molecular resolution. Nat. Commun. 2023, 14, 5799, DOI: 10.1038/s41467-023-41417-0There is no corresponding record for this reference.
- 430Qu, J.; Xie, Y. R.; Ciesielski, K. M.; Porter, C. E.; Toberer, E. S.; Ertekin, E. Leveraging language representation for materials exploration and discovery. npj Computational Materials 2024, 10, 58, DOI: 10.1038/s41524-024-01231-8There is no corresponding record for this reference.
- 431Martin, F. L.; Kelly, J. G.; Llabjani, V.; Martin-Hirsch, P. L.; Patel, I. I.; Trevisan, J.; Fullwood, N. J.; Walsh, M. J. Distinguishing cell types or populations based on the computational analysis of their infrared spectra. Nat. Protoc 2010, 5, 1748– 1760, DOI: 10.1038/nprot.2010.133431Distinguishing cell types or populations based on the computational analysis of their infrared spectraMartin, Francis L.; Kelly, Jemma G.; Llabjani, Valon; Martin-Hirsch, Pierre L.; Patel, Imran I.; Trevisan, Julio; Fullwood, Nigel J.; Walsh, Michael J.Nature Protocols (2010), 5 (11), 1748-1760CODEN: NPARDW; ISSN:1750-2799. (Nature Publishing Group)IR (IR) spectroscopy of intact cells results in a fingerprint of their biochem. in the form of an IR spectrum; this has given rise to the new field of biospectroscopy. This protocol describes sample prepn. (a tissue section or cytol. specimen), the application of IR spectroscopy tools, and computational anal. Exptl. considerations include optimization of specimen prepn., objective acquisition of a sufficient no. of spectra, linking of the derived spectra with tissue architecture or cell type, and computational anal. The prepn. of multiple specimens (up to 50) takes 8 h; the interrogation of a tissue section can take up to 6 h (∼100 spectra); and cytol. anal. (n = 50, 10 spectra per specimen) takes 14 h. IR spectroscopy generates complex data sets and analyses are best when initially based on a multivariate approach (principal component anal. with or without linear discriminant anal.). This results in the identification of class clustering as well as class-specific chem. entities.
- 432Leong, S. X.; Tan, E. X.; Han, X.; Luhung, I.; Aung, N. W.; Nguyen, L. B. T.; Tan, S. Y.; Li, H.; Phang, I. Y.; Schuster, S.; Ling, X. Y. Surface-Enhanced Raman Scattering-Based Surface Chemotaxonomy: Combining Bacteria Extracellular Matrices and Machine Learning for Rapid and Universal Species Identification. ACS Nano 2023, 17, 23132– 23143, DOI: 10.1021/acsnano.3c09101There is no corresponding record for this reference.
- 433Del Villar-Guerra, R.; Trent, J. O.; Chaires, J. B. G-Quadruplex Secondary Structure Obtained from Circular Dichroism Spectroscopy. Angew. Chem., Int. Ed. Engl. 2018, 57, 7171– 7175, DOI: 10.1002/anie.201709184433G-Quadruplex Secondary Structure Obtained from Circular Dichroism SpectroscopyDel Villar-Guerra Rafael; Trent John O; Chaires Jonathan BAngewandte Chemie (International ed. in English) (2018), 57 (24), 7171-7175 ISSN:.A curated library of circular dichroism spectra of 23 G-quadruplexes of known structure was built and analyzed. The goal of this study was to use this reference library to develop an algorithm to derive quantitative estimates of the secondary structure content of quadruplexes from their experimental CD spectra. Principal component analysis and singular value decomposition were used to characterize the reference spectral library. CD spectra were successfully fit to obtain estimates of the amounts of base steps in anti-anti, syn-anti or anti-syn conformations, in diagonal or lateral loops, or in other conformations. The results show that CD spectra of nucleic acids can be analyzed to obtain quantitative structural information about secondary structure content in an analogous way to methods used to analyze protein CD spectra.
- 434Leong, S. X.; Koh, C. S. L.; Sim, H. Y. F.; Lee, Y. H.; Han, X.; Phan-Quang, G. C.; Ling, X. Y. Enantiospecific Molecular Fingerprinting Using Potential-Modulated Surface-Enhanced Raman Scattering to Achieve Label-Free Chiral Differentiation. ACS Nano 2021, 15, 1817– 1825, DOI: 10.1021/acsnano.0c09670434Enantiospecific Molecular Fingerprinting Using Potential-Modulated Surface-Enhanced Raman Scattering to Achieve Label-Free Chiral DifferentiationLeong, Shi Xuan; Koh, Charlynn Sher Lin; Sim, Howard Yi Fan; Lee, Yih Hong; Han, Xuemei; Phan-Quang, Gia Chuong; Ling, Xing YiACS Nano (2021), 15 (1), 1817-1825CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Chiral differentiation is crit. in diverse fields ranging from pharmaceutics to chiral synthesis. While surface-enhanced Raman scattering (SERS) offers mol.-specific vibrational information with high detection sensitivity, current strategies rely on indirect detection using addnl. selectors and cannot exploit SERS' key advantages for univocal and generic chiral differentiation. Here, we achieve direct, label-free SERS sensing of biol. important enantiomers by synergizing asym. nanoporous gold (NPG) nanoparticles with electrochem.-SERS to generate enantiospecific mol. fingerprints. Exptl. and in silico studies reveal that chiral recognition is two pronged. First, the numerous surface at. defects in NPG provide the necessary localized asym. environment to induce enantiospecific mol. adsorptions and interaction affinities. Concurrently, the applied potential drives and orients the enantiomers close to the NPG surface for maximal analyte-surface interactions. Notably, our strategy is versatile and can be readily extended to detect various enantiomers. Furthermore, we can achieve multiplex quantification of enantiomeric ratios with excellent predictive performance. Our combinatorial approach thus offers an important paradigm shift from current approaches to achieve label-free chiral SERS sensing of various enantiomers.
- 435Leong, S. X.; Leong, Y. X.; Tan, E. X.; Sim, H. Y. F.; Koh, C. S. L.; Lee, Y. H.; Chong, C.; Ng, L. S.; Chen, J. R. T.; Pang, D. W. C.; Nguyen, L. B. T.; Boong, S. K.; Han, X.; Kao, Y.-C.; Chua, Y. H.; Phan-Quang, G. C.; Phang, I. Y.; Lee, H. K.; Abdad, M. Y.; Tan, N. S.; Ling, X. Y. Noninvasive and Point-of-Care Surface-Enhanced Raman Scattering (SERS)-Based Breathalyzer for Mass Screening of Coronavirus Disease 2019 (COVID-19) under 5 min. ACS Nano 2022, 16, 2629– 2639, DOI: 10.1021/acsnano.1c09371435Noninvasive and Point-of-Care Surface-Enhanced Raman Scattering (SERS)-Based Breathalyzer for Mass Screening of Coronavirus Disease 2019 (COVID-19) under 5 minLeong, Shi Xuan; Leong, Yong Xiang; Tan, Emily Xi; Sim, Howard Yi Fan; Koh, Charlynn Sher Lin; Lee, Yih Hong; Chong, Carice; Ng, Li Shiuan; Chen, Jaslyn Ru Ting; Pang, Desmond Wei Cheng; Nguyen, Lam Bang Thanh; Boong, Siew Kheng; Han, Xuemei; Kao, Ya-Chuan; Chua, Yi Heng; Phan-Quang, Gia Chuong; Phang, In Yee; Lee, Hiang Kwee; Abdad, Mohammad Yazid; Tan, Nguan Soon; Ling, Xing YiACS Nano (2022), 16 (2), 2629-2639CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Population-wide surveillance of COVID-19 requires tests to be quick and accurate to minimize community transmissions. The detection of breath volatile org. compds. presents a promising option for COVID-19 surveillance but is currently limited by bulky instrumentation and inflexible anal. protocol. Here, we design a hand-held surface-enhanced Raman scattering-based breathalyzer to identify COVID-19 infected individuals in under 5 min, achieving >95% sensitivity and specificity across 501 participants regardless of their displayed symptoms. Our SERS-based breathalyzer harnesses key variations in vibrational fingerprints arising from interactions between breath metabolites and multiple mol. receptors to establish a robust partial least-squares discriminant anal. model for high throughput classifications. Crucially, spectral regions influencing classification show strong corroboration with reported potential COVID-19 breath biomarkers, both through expt. and in silico. Our strategy strives to spur the development of next-generation, noninvasive human breath diagnostic toolkits tailored for mass screening purposes.
- 436Kao, Y.-C.; Han, X.; Lee, Y. H.; Lee, H. K.; Phan-Quang, G. C.; Lay, C. L.; Sim, H. Y. F.; Phua, V. J. X.; Ng, L. S.; Ku, C. W.; Tan, T. C.; Phang, I. Y.; Tan, N. S.; Ling, X. Y. Multiplex Surface-Enhanced Raman Scattering Identification and Quantification of Urine Metabolites in Patient Samples within 30 min. ACS Nano 2020, 14, 2542– 2552, DOI: 10.1021/acsnano.0c00515436Multiplex Surface-Enhanced Raman Scattering Identification and Quantification of Urine Metabolites in Patient Samples within 30 minKao, Ya-Chuan; Han, Xuemei; Lee, Yih Hong; Lee, Hiang Kwee; Phan-Quang, Gia Chuong; Lay, Chee Leng; Sim, Howard Yi Fan; Phua, Vanessa Jing Xin; Ng, Li Shiuan; Ku, Chee Wai; Tan, Thiam Chye; Phang, In Yee; Tan, Nguan Soon; Ling, Xing YiACS Nano (2020), 14 (2), 2542-2552CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Successful translation of lab.-based surface-enhanced Raman scattering (SERS) platforms to clin. applications requires multiplex and ultratrace detection of small biomarker mols. from a complex biofluid. However, these biomarker mols. generally exhibit low Raman scattering cross sections and do not possess specific affinity to plasmonic nanoparticle surfaces, significantly increasing the challenge of detecting them at low concns. Herein, we demonstrate a "confine-and-capture" approach for multiplex detection of two families of urine metabolites correlated with miscarriage risks, 5β-pregnane-3α,20α-diol-3α-glucuronide and tetrahydrocortisone. To enhance SERS signals by 1012-fold, we use specific nanoscale surface chem. for targeted metabolite capture from a complex urine matrix prior to confining them on a superhydrophobic SERS platform. We then apply chemometrics, including principal component anal. and partial least-squares regression, to convert mol. fingerprint information into quantifiable readouts. The whole screening procedure requires only 30 min, including urine pretreatment, sample drying on the SERS platform, SERS measurements, and chemometric analyses. These readouts correlate well with the pregnancy outcomes in a case-control study of 40 patients presenting threatened miscarriage symptoms.
- 437Kim, W.; Lee, S. H.; Kim, J. H.; Ahn, Y. J.; Kim, Y. H.; Yu, J. S.; Choi, S. Paper-Based Surface-Enhanced Raman Spectroscopy for Diagnosing Prenatal Diseases in Women. ACS Nano 2018, 12, 7100– 7108, DOI: 10.1021/acsnano.8b02917437Paper-Based Surface-Enhanced Raman Spectroscopy for Diagnosing Prenatal Diseases in WomenKim, Wansun; Lee, Soo Hyun; Kim, Jin Hwi; Ahn, Yong Jin; Kim, Yeon-Hee; Yu, Jae Su; Choi, SamjinACS Nano (2018), 12 (7), 7100-7108CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)The authors report the development of a surface-enhanced Raman spectroscopy sensor chip by decorating gold nanoparticles (AuNPs) on ZnO nanorod (ZnO NR) arrays vertically grown on cellulose paper (C). These chips can enhance the Raman signal by 1.25 × 107 with an excellent reproducibility of <6%. The authors can measure trace amts. of human amniotic fluids of patients with subclin. intra-amniotic infection (IAI) and preterm delivery (PTD) using the chip in combination with a multivariate statistics-derived machine-learning-trained bioclassification method. The authors can detect the presence of prenatal diseases and identify the types of diseases from amniotic fluids with >92% clin. sensitivity and specificity. The authors' technol. has the potential to be used for the early detection of prenatal diseases and can be adapted for point-of-care applications.
- 438Torrisi, S. B.; Carbone, M. R.; Rohr, B. A.; Montoya, J. H.; Ha, Y.; Yano, J.; Suram, S. K.; Hung, L. Random forest machine learning models for interpretable X-ray absorption near-edge structure spectrum-property relationships. npj Computational Materials 2020, 6, 109, DOI: 10.1038/s41524-020-00376-6There is no corresponding record for this reference.
- 439Chen, B.; Sheridan, R. P.; Hornak, V.; Voigt, J. H. Comparison of random forest and Pipeline Pilot Naïve Bayes in prospective QSAR predictions. J. Chem. Inf Model 2012, 52, 792– 803, DOI: 10.1021/ci200615h439Comparison of Random Forest and Pipeline Pilot Naive Bayes in Prospective QSAR PredictionsChen, Bin; Sheridan, Robert P.; Hornak, Viktor; Voigt, Johannes H.Journal of Chemical Information and Modeling (2012), 52 (3), 792-803CODEN: JCISD8; ISSN:1549-9596. (American Chemical Society)Random forest is currently considered one of the best QSAR methods available in terms of accuracy of prediction. However, it is computationally intensive. Naive Bayes is a simple, robust classification method. The Laplacian-modified Naive Bayes implementation is the preferred QSAR method in the widely used com. chemoinformatics platform Pipeline Pilot. We made a comparison of the ability of Pipeline Pilot Naive Bayes (PLPNB) and random forest to make accurate predictions on 18 large, diverse inhouse QSAR data sets. These include on-target and ADME-related activities. These data sets were set up as classification problems with either binary or multicategory activities. We used a time-split method of dividing training and test sets, as we feel this is a realistic way of simulating prospective prediction. PLPNB is computationally efficient. However, random forest predictions are at least as good and in many cases significantly better than those of PLPNB on our data sets. PLPNB performs better with ECFP4 and ECFP6 descriptors, which are native to Pipeline Pilot, and more poorly with other descriptors we tried.
- 440Sheridan, R. P.; Wang, W. M.; Liaw, A.; Ma, J.; Gifford, E. M. Extreme Gradient Boosting as a Method for Quantitative Structure-Activity Relationships. J. Chem. Inf Model 2016, 56, 2353– 2360, DOI: 10.1021/acs.jcim.6b00591440Extreme Gradient Boosting as a Method for Quantitative Structure-Activity RelationshipsSheridan, Robert P.; Wang, Wei Min; Liaw, Andy; Ma, Junshui; Gifford, Eric M.Journal of Chemical Information and Modeling (2016), 56 (12), 2353-2360CODEN: JCISD8; ISSN:1549-9596. (American Chemical Society)In the pharmaceutical industry it is common to generate many QSAR models from training sets contg. a large no. of mols. and a large no. of descriptors. The best QSAR methods are those that can generate the most accurate predictions but that are not overly expensive computationally. In this paper the authors compare extreme gradient boosting (XGBoost) to random forest and single-task deep neural nets on 30 inhouse data sets. While XGBoost has many adjustable parameters, the authors can define a set of std. parameters at which XGBoost makes predictions, on the av., better than those of random forest and almost as good as those of deep neural nets. The biggest strength of XGBoost is its speed. Whereas efficient use of random forest requires generating each tree in parallel on a cluster, and deep neural nets are usually run on GPUs, XGBoost can be run on a single cluster CPU in less than a third of the wall-clock time of either of the other methods.
- 441Schleder, G. R.; Acosta, C. M.; Fazzio, A. Exploring Two-Dimensional Materials Thermodynamic Stability via Machine Learning. ACS Appl. Mater. Interfaces 2020, 12, 20149– 20157, DOI: 10.1021/acsami.9b14530441Exploring Two-Dimensional Materials Thermodynamic Stability via Machine LearningSchleder, Gabriel R.; Acosta, Carlos Mera; Fazzio, AdalbertoACS Applied Materials & Interfaces (2020), 12 (18), 20149-20157CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)The increasing interest and research on two-dimensional (2D) materials has not yet translated into a reality of diverse materials applications. To go beyond graphene and transition metal dichalcogenides for several applications, suitable candidates with desirable properties must be proposed. Here we use machine learning techniques to identify thermodynamically stable 2D materials, which is the first essential requirement for any application. According to the formation energy and energy above the convex hull, we classify materials as having low, medium, or high stability. The proposed approach enables the stability evaluation of novel 2D compds. for further detailed investigation of promising candidates, using only compn. properties and structural symmetry, without the need for information about at. positions. We demonstrate the usefulness of the model generating more than a thousand novel compds., corroborating with DFT calcns. the classification for five of these materials. To illustrate the applicability of the stable materials, we then perform a screening of electronic materials suitable for photoelectrocatalytic water splitting, identifying the potential candidate Sn2SeTe generated by our model, and also PbTe, both not yet reported for this application.
- 442Ahmad, Z.; Xie, T.; Maheshwari, C.; Grossman, J. C.; Viswanathan, V. Machine Learning Enabled Computational Screening of Inorganic Solid Electrolytes for Suppression of Dendrite Formation in Lithium Metal Anodes. ACS Cent. Sci. 2018, 4, 996– 1006, DOI: 10.1021/acscentsci.8b00229442Machine Learning Enabled Computational Screening of Inorganic Solid Electrolytes for Suppression of Dendrite Formation in Lithium Metal AnodesAhmad, Zeeshan; Xie, Tian; Maheshwari, Chinmay; Grossman, Jeffrey C.; Viswanathan, VenkatasubramanianACS Central Science (2018), 4 (8), 996-1006CODEN: ACSCII; ISSN:2374-7951. (American Chemical Society)Next generation batteries based on lithium (Li) metal anodes have been plagued by the dendritic electrodeposition of Li metal on the anode during cycling, resulting in short circuit and capacity loss. Suppression of dendritic growth through the use of solid electrolytes has emerged as one of the most promising strategies for enabling the use of Li metal anodes. We perform a computational screening of over 12000 inorg. solids based on their ability to suppress dendrite initiation in contact with Li metal anode. Properties for mech. isotropic and anisotropic interfaces that can be used in stability criteria for detg. the propensity of dendrite initiation are usually obtained from computationally expensive first-principles methods. In order to obtain a large data set for screening, we use machine-learning models to predict the mech. properties of several new solid electrolytes. The machine-learning models are trained on purely structural features of the material, which do not require any first-principles calcns. We train a graph convolutional neural network on the shear and bulk moduli because of the availability of a large training data set with low noise due to low uncertainty in their first-principles-calcd. values. We use gradient boosting regressor and kernel ridge regression to train the elastic consts., where the choice of the model depends on the size of the training data and the noise that it can handle. The material stiffness is found to increase with an increase in mass d. and ratio of Li and sublattice bond ionicity, and decrease with increase in vol. per atom and sublattice electronegativity. Cross-validation/test performance suggests our models generalize well. We predict over 20 mech. anisotropic interfaces between Li metal and four solid electrolytes which can be used to suppress dendrite growth. Our screened candidates are generally soft and highly anisotropic, and present opportunities for simultaneously obtaining dendrite suppression and high ionic cond. in solid electrolytes.
- 443Tamtaji, M.; Guo, X.; Tyagi, A.; Galligan, P. R.; Liu, Z.; Roxas, A.; Liu, H.; Cai, Y.; Wong, H.; Zeng, L.; Xie, J.; Du, Y.; Hu, Z.; Lu, D.; Goddard, W. A., III; Zhu, Y.; Luo, Z. Machine Learning-Aided Design of Gold Core–Shell Nanocatalysts toward Enhanced and Selective Photooxygenation. ACS Appl. Mater. Interfaces 2022, 14, 46471– 46480, DOI: 10.1021/acsami.2c11101443Machine Learning-Aided Design of Gold Core-Shell Nanocatalysts toward Enhanced and Selective PhotooxygenationTamtaji, Mohsen; Guo, Xuyun; Tyagi, Abhishek; Galligan, Patrick Ryan; Liu, Zhenjing; Roxas, Alexander; Liu, Hongwei; Cai, Yuting; Wong, Hoilun; Zeng, Lun; Xie, Jianbo; Du, Yucong; Hu, Zhigang; Lu, Dong; Goddard III, William A.; Zhu, Ye; Luo, ZhengtangACS Applied Materials & Interfaces (2022), 14 (41), 46471-46480CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)We demonstrate the use of the machine learning (ML) tools to rapidly and accurately predict the elec. field as a guide for designing core-shell Au-silica nanoparticles to enhance 1O2 sensitization and selectivity of org. synthesis. Based on the feature importance anal., obtained from a deep neural network algorithm, we found a general and linear dependent descriptor (θ aD0.25t-1, where a, D, and t are the shape const., size of metal nanoparticles, and distance from the metal surface) for the elec. field around the core-shell plasmonic nanoparticle. Directed by the new descriptor, we synthesized gold-silica nanoparticles and validated their plasmonic intensity using scanning transmission electron microscopy-electron energy loss spectroscopy (STEM-EELS) mapping. The nanoparticles with θ = 0.40 demonstrate an ~ 3-fold increase in the reaction rate of photooxygenation of anthracene and 4% increase in the selectivity of photooxygenation of dihydroartemisinic acid (DHAA), a long-standing goal in org. synthesis. In addn., the combination of ML and exptl. investigations shows the synergetic effect of plasmonic enhancement and fluorescence quenching, leading to enhancement for 1O2 generation. Our results from time-dependent d. functional theory (TD-DFT) calcns. suggest that the presence of an elec. field can favor intersystem crossing (ISC) of methylene blue to enhance 1O2 generation. The strategy reported here provides a data-driven catalyst prepn. method that can significantly reduce exptl. cost while paving the way for designing photocatalysts for org. drug synthesis.
- 444Lussier, F.; Missirlis, D.; Spatz, J. P.; Masson, J.-F. Machine-Learning-Driven Surface-Enhanced Raman Scattering Optophysiology Reveals Multiplexed Metabolite Gradients Near Cells. ACS Nano 2019, 13, 1403– 1411, DOI: 10.1021/acsnano.8b07024444Machine-Learning-Driven Surface-Enhanced Raman Scattering Optophysiology Reveals Multiplexed Metabolite Gradients Near CellsLussier, Felix; Missirlis, Dimitris; Spatz, Joachim P.; Masson, Jean-FrancoisACS Nano (2019), 13 (2), 1403-1411CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)The extracellular environment is a complex medium in which cells secrete and consume metabolites. Mol. gradients are thereby created near cells, triggering various biol. and physiol. responses. However, investigating these mol. gradients remains challenging because the current tools are ill-suited and provide poor temporal and special resoln. while also being destructive. Herein, the authors report the development and application of a machine learning approach in combination with a surface-enhanced Raman spectroscopy (SERS) nanoprobe to measure simultaneously the gradients of at least eight metabolites in vitro near different cell lines. The authors found significant increase in the secretion or consumption of lactate, glucose, ATP, glutamine, and urea within 20 μm from the cells surface compared to the bulk. The authors also obsd. that cancerous cells (HeLa) compared to fibroblasts (REF52) have a greater glycolytic rate, as is expected for this phenotype. Endothelial (HUVEC) and HeLa cells exhibited significant increase in extracellular ATP compared to the control, shining light on the implication of extracellular ATP within the cancer local environment. Machine-learning-driven SERS optophysiol. is generally applicable to metabolites involved in cellular processes, providing a general platform on which to study cell biol.
- 445Shin, H.; Choi, B. H.; Shim, O.; Kim, J.; Park, Y.; Cho, S. K.; Kim, H. K.; Choi, Y. Single test-based diagnosis of multiple cancer types using Exosome-SERS-AI for early stage cancers. Nat. Commun. 2023, 14, 1644, DOI: 10.1038/s41467-023-37403-1445Single test-based diagnosis of multiple cancer types using Exosome-SERS-AI for early stage cancersShin, Hyunku; Choi, Byeong Hyeon; Shim, On; Kim, Jihee; Park, Yong; Cho, Suk Ki; Kim, Hyun Koo; Choi, YeonhoNature Communications (2023), 14 (1), 1644CODEN: NCAOBW; ISSN:2041-1723. (Nature Portfolio)Early cancer detection has significant clin. value, but there remains no single method that can comprehensively identify multiple types of early-stage cancer. Here, we report the diagnostic accuracy of simultaneous detection of 6 types of early-stage cancers (lung, breast, colon, liver, pancreas, and stomach) by analyzing surface-enhanced Raman spectroscopy profiles of exosomes using artificial intelligence in a retrospective study design. It includes classification models that recognize signal patterns of plasma exosomes to identify both their presence and tissues of origin. Using 520 test samples, our system identified cancer presence with an area under the curve value of 0.970. Moreover, the system classified the tumor organ type of 278 early-stage cancer patients with a mean area under the curve of 0.945. The final integrated decision model showed a sensitivity of 90.2% at a specificity of 94.4% while predicting the tumor organ of 72% of pos. patients. Since our method utilizes a non-specific anal. of Raman signatures, its diagnostic scope could potentially be expanded to include other diseases.
- 446Kalinin, S. V.; Kelley, K.; Vasudevan, R. K.; Ziatdinov, M. Toward Decoding the Relationship between Domain Structure and Functionality in Ferroelectrics via Hidden Latent Variables. ACS Appl. Mater. Interfaces 2021, 13, 1693– 1703, DOI: 10.1021/acsami.0c15085446Toward decoding relationship between domain structure and functionality in ferroelectrics via hidden latent variablesKalinin, Sergei V.; Kelley, Kyle; Vasudevan, Rama K.; Ziatdinov, MaximACS Applied Materials & Interfaces (2021), 13 (1), 1693-1703CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Polarization switching mechanisms in ferroelec. materials are fundamentally linked to local domain structure and the presence of the structural defects, which both can act as nucleation and pinning centers and create local electrostatic and mech. depolarization fields affecting wall dynamics. However, the general correlative mechanisms between domain structure and polarization dynamics are only weakly explored, precluding insight into the assocd. phys. mechanisms. Here, the correlation between local domain structures and switching behavior in ferroelec. materials is explored using convolutional encoder-decoder networks, enabling image to spectral (i.m.2spec) and spectral to image (spec2i.m.) translations via encoding of latent variables. The latter reflect the assumption that the relationship between domain structure and polarization switching is parsimonious, i.e., is based upon a small no. of local mechanisms. The anal. of latent variables distributions and their real-space representations provides insight into the predictability of the local switching behavior and hence assocd. phys. mechanisms. We further pose that the regions where these correlative relationships are violated, i.e., predictability of the polarization dynamics from domain structure is reduced, represent the obvious target for detailed studies, e.g., in the context of automated expts. This approach provides a workflow to establish the presence of correlation between local spectral responses and local structure and can be universally applied to spectral imaging techniques such as piezoresponse force microscopy (PFM), scanning tunneling microscopy (STM) and spectroscopy, and electron energy loss spectroscopy (EELS) in scanning transmission electron microscopy (STEM).
- 447Moses, I. A.; Joshi, R. P.; Ozdemir, B.; Kumar, N.; Eickholt, J.; Barone, V. Machine Learning Screening of Metal-Ion Battery Electrode Materials. ACS Appl. Mater. Interfaces 2021, 13, 53355– 53362, DOI: 10.1021/acsami.1c04627447Machine Learning Screening of Metal-Ion Battery Electrode MaterialsMoses, Isaiah A.; Joshi, Rajendra P.; Ozdemir, Burak; Kumar, Neeraj; Eickholt, Jesse; Barone, VeronicaACS Applied Materials & Interfaces (2021), 13 (45), 53355-53362CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Rechargeable batteries provide crucial energy storage systems for renewable energy sources, as well as consumer electronics and elec. vehicles. There are a no. of important parameters that det. the suitability of electrode materials for battery applications, such as the av. voltage and the max. specific capacity which contribute to the overall energy d. Another important performance criterion for battery electrode materials is their vol. change upon charging and discharging, which contributes to det. the cyclability, Coulombic efficiency, and safety of a battery. In this work, we present deep neural network regression machine learning models (ML), trained on data obtained from the Materials Project database, for predicting av. voltages and vol. change upon charging and discharging of electrode materials for metal-ion batteries. Our models exhibit good performance as measured by the av. mean abs. error obtained from a 10-fold cross-validation, as well as on independent test sets. We further assess the robustness of our ML models by investigating their screening potential beyond the training database. We produce Na-ion electrodes by systematically replacing Li-ions in the original database by Na-ions and, then, selecting a set of 22 electrodes that exhibit a good performance in energy d., as well as small vol. variations upon charging and discharging, as predicted by the machine learning model. The ML predictions for these materials are then compared to quantum-mechanics based calcns. Our results reaffirm the significant role of machine learning techniques in the exploration of materials for battery applications.
- 448Garg, A.; Nam, W.; Wang, W.; Vikesland, P.; Zhou, W. In Situ Spatiotemporal SERS Measurements and Multivariate Analysis of Virally Infected Bacterial Biofilms Using Nanolaminated Plasmonic Crystals. ACS Sensors 2023, 8, 1132– 1142, DOI: 10.1021/acssensors.2c02412There is no corresponding record for this reference.
- 449Matschulat, A.; Drescher, D.; Kneipp, J. Surface-Enhanced Raman Scattering Hybrid Nanoprobe Multiplexing and Imaging in Biological Systems. ACS Nano 2010, 4, 3259– 3269, DOI: 10.1021/nn100280z449Surface-Enhanced Raman Scattering Hybrid Nanoprobe Multiplexing and Imaging in Biological SystemsMatschulat, Andrea; Drescher, Daniela; Kneipp, JaninaACS Nano (2010), 4 (6), 3259-3269CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Surface-enhanced Raman scattering (SERS) labels and probes consisting of gold and silver nanoaggregates and attached reporter mols. can be identified by the Raman signature of the reporter mol. At the same time, SERS hybrid probes deliver sensitive mol. structural information on their nanoenvironment. Here the authors demonstrate full exploitation of the multifunctional and multiplexing capabilities inherent to such nanoprobes by applying cluster methods and principal components approaches for discrimination beyond the visual inspection of individual spectra that has been practiced so far. The reported results indicate that fast, multivariate evaluation of whole sets of multiple probes is feasible. Spectra of five different reporters were shown to be separable by hierarchical clustering and by principal components anal. (PCA). In a duplex imaging approach in live cells, hierarchical cluster anal., K-means clustering, and PCA were used for imaging the positions of different types of SERS probes along with the spectral information from cellular constituents. Parallel to cellular imaging expts., cytotoxicity of the SERS hybrid probes contg. arom. thiols as reporters is assessed. The reported results suggest multiplexing applications of the nontoxic SERS nanoprobes in high d. sensing and imaging in complex biol. structures.
- 450Meunier, C. J.; McCarty, G. S.; Sombers, L. A. Drift Subtraction for Fast-Scan Cyclic Voltammetry Using Double-Waveform Partial-Least-Squares Regression. Anal. Chem. 2019, 91, 7319– 7327, DOI: 10.1021/acs.analchem.9b01083There is no corresponding record for this reference.
- 451Wang, M.; Xu, Q.; Tang, H.; Jiang, J. Machine Learning-Enabled Prediction and High-Throughput Screening of Polymer Membranes for Pervaporation Separation. ACS Appl. Mater. Interfaces 2022, 14, 8427– 8436, DOI: 10.1021/acsami.1c22886451Machine Learning-Enabled Prediction and High-Throughput Screening of Polymer Membranes for Pervaporation SeparationWang, Mao; Xu, Qisong; Tang, Hongjian; Jiang, JianwenACS Applied Materials & Interfaces (2022), 14 (6), 8427-8436CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Pervaporation (PV) is considered as a robust membrane-based sepn. technol. for liq. mixts. However, the development of PV membranes is impeded largely by the lack of adequate models capable of reliably predicting the performance of PV membranes. In this study, we collect an exptl. data set with a total of 681 data samples including 16 polymers and 6 org. solvents for a wide variety of water/org. mixts. under various operating conditions. Then, two types of machine learning (ML) models are developed for prediction and high-throughput screening of polymer membranes for PV sepn. Based on the intrinsic properties of polymer and solvent (water contact angle of polymer and soly. parameter of solvent) as gross descriptors, the first type accurately predicts PV sepn. performance (total flux and sepn. factor). The second type is based on the mol. representation of polymer and solvent, giving accuracy comparable to the first type, and applied to screen ~ 1 million hypothetical polymers for PV sepn. of water/ethanol mixts. With a threshold of 700 for the PV sepn. index, 20 polymers are short listed, with many surpassing exptl. samples. Among these, 10 are further identified to be synthesizable in terms of a synthetic complexity score. The ML models developed in this study would facilitate the optimization of operating conditions and accelerate the development of new polymer membranes for high-performance PV sepn.
- 452Acosta, C. M.; Ogoshi, E.; Souza, J. A.; Dalpian, G. M. Machine Learning Study of the Magnetic Ordering in 2D Materials. ACS Appl. Mater. Interfaces 2022, 14, 9418– 9432, DOI: 10.1021/acsami.1c21558452Machine Learning Study of the Magnetic Ordering in 2D MaterialsAcosta Carlos Mera; Ogoshi Elton; Souza Jose Antonio; Dalpian Gustavo MACS applied materials & interfaces (2022), 14 (7), 9418-9432 ISSN:.Magnetic materials have been applied in a large variety of technologies, from data storage to quantum devices. The development of two-dimensional (2D) materials has opened new arenas for magnetic compounds, even when classical theories discourage their examination. Here we propose a machine-learning-based strategy to predict and understand magnetic ordering in 2D materials. This strategy couples the prediction of the existence of magnetism in 2D materials using a random forest and the Shapley additive explanations method with material maps defined by atomic features predicting the magnetic ordering (ferromagnetic or antiferromagnetic). While the random forest model predicts magnetism with an accuracy of 86%, the material maps obtained by the sure independence screening and sparsifying method have an accuracy of ∼90% in predicting the magnetic ordering. Our model indicates that 3d transition metals, halides, and structural clusters with regular transition-metal sublattices have a positive contribution in the total weight deciding the existence of magnetism in 2D compounds. This behavior is associated with the competition between crystal field and exchange splitting. The machine learning model also indicates that the atomic spin orbit coupling (SOC) is a determinant feature for the identification of the patterns separating ferro- from antiferromagnetic order. The proposed strategy is used to identify novel 2D magnetic compounds that, together with the fundamental trends in the chemical and structural space, pave novel routes for experimental exploration.
- 453Hu, W.; Zhang, L.; Pan, Z. Designing Two-Dimensional Halide Perovskites Based on High-Throughput Calculations and Machine Learning. ACS Appl. Mater. Interfaces 2022, 14, 21596– 21604, DOI: 10.1021/acsami.2c00564453Designing Two-Dimensional Halide Perovskites Based on High-Throughput Calculations and Machine LearningHu, Wenguang; Zhang, Lei; Pan, ZhengACS Applied Materials & Interfaces (2022), 14 (18), 21596-21604CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)The interactions between ions and the low-dimensional halide perovskites are crit. to realizing the next-generation energy storage devices such as photorechargeable ion batteries and ion capacitors. In this study, we performed high-throughput calcns. and machine-learning anal. for ion adsorption on two-dimensional A2BX4 halide perovskites. The first-principles calcns. obtained an initial data set contg. adsorption energies of 640 compositionally engineered ion/perovskite systems with diverse ions including Li+, Zn2+, K+, Na+, Al3+, Ca2+, Mg2+, and F-. The machine learning algorithms including k-nearest neighbors (KNN), Kriging, Random Forest, Rpart, SVM, and Xgboost algorithms were compared, and the Xgboost algorithm achieved the best accuracy (r = 0.97, R2 = 0.93) and was selected to predict the virtual design space consisting of 11 976 ion/perovskite systems. The features were then analyzed and ranked according to their Pearson correlations to the output values. In particular, to better understand the features, diverse feature selection methods were employed to comprehensively evaluate the features. The machine-learning-predicted virtual design space was subsequently screened to select stable lead-free ion/perovskite systems with suitable band gaps and halogen mixing features. The present study provides a theor. foundation to design halide perovskite materials for ion-based energy storage applications such as secondary ion batteries, ion capacitors, and solar-rechargeable batteries.
- 454Alobaidi, M.; Malik, K. M.; Sabra, S. Linked open data-based framework for automatic biomedical ontology generation. BMC Bioinformatics 2018, 19, 319, DOI: 10.1186/s12859-018-2339-3There is no corresponding record for this reference.
- 455Lu, M.; Gao, F.; Tan, Y.; Yi, H.; Gui, Y.; Xu, Y.; Wang, Y.; Zhou, Y.; Tang, X.; Chen, L. Knowledge-Driven Experimental Discovery of Ce-Based Metal Oxide Composites for Selective Catalytic Reduction of NOx with NH3 through Interpretable Machine Learning. ACS Appl. Mater. Interfaces 2024, 16, 3593– 3604, DOI: 10.1021/acsami.3c18490There is no corresponding record for this reference.
- 456Huang, Y.; Li, S.; Zhang, L. Accelerated Multisolvent Prediction for Aqueous Stable Halide Perovskite Materials. ACS Appl. Mater. Interfaces 2023, 15, 48771– 48784, DOI: 10.1021/acsami.3c09507There is no corresponding record for this reference.
- 457Kumar, A.; Islam, M. R.; Zughaier, S. M.; Chen, X.; Zhao, Y. Precision classification and quantitative analysis of bacteria biomarkers via surface-enhanced Raman spectroscopy and machine learning. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 2024, 320, 124627, DOI: 10.1016/j.saa.2024.124627There is no corresponding record for this reference.
- 458Rosa, L. C. S.; Argolo, C. O.; Nascimento, C. M. C.; Pimentel, A. S. Identifying Substructures That Facilitate Compounds to Penetrate the Blood-Brain Barrier via Passive Transport Using Machine Learning Explainer Models. ACS Chem. Neurosci. 2024, 15, 2144– 2159, DOI: 10.1021/acschemneuro.3c00840There is no corresponding record for this reference.
- 459Wellawatte, G. P.; Gandhi, H. A.; Seshadri, A.; White, A. D. A Perspective on Explanations of Molecular Prediction Models. J. Chem. Theory Comput. 2023, 19, 2149– 2160, DOI: 10.1021/acs.jctc.2c01235459A Perspective on Explanations of Molecular Prediction ModelsWellawatte, Geemi P.; Gandhi, Heta A.; Seshadri, Aditi; White, Andrew D.Journal of Chemical Theory and Computation (2023), 19 (8), 2149-2160CODEN: JCTCCE; ISSN:1549-9618. (American Chemical Society)A review. Chemists can be skeptical in using deep learning (DL) in decision making, due to the lack of interpretability in "black-box" models. Explainable artificial intelligence (XAI) is a branch of artificial intelligence (AI) which addresses this drawback by providing tools to interpret DL models and their predictions. We review the principles of XAI in the domain of chem. and emerging methods for creating and evaluating explanations. Then, we focus on methods developed by our group and their applications in predicting soly., blood-brain barrier permeability, and the scent of mols. We show that XAI methods like chem. counterfactuals and descriptor explanations can explain DL predictions while giving insight into structure-property relationships. Finally, we discuss how a two-step process of developing a black-box model and explaining predictions can uncover structure-property relationships.
- 460Wang, S.; Jiang, J. Interpretable Catalysis Models Using Machine Learning with Spectroscopic Descriptors. ACS Catal. 2023, 13, 7428– 7436, DOI: 10.1021/acscatal.3c00611460Interpretable Catalysis Models Using Machine Learning with Spectroscopic DescriptorsWang, Song; Jiang, JunACS Catalysis (2023), 13 (11), 7428-7436CODEN: ACCACS; ISSN:2155-5435. (American Chemical Society)The complexity and dynamics of catalytic systems make it challenging to study the catalysts and catalytic reactions. Fortunately, the advance of machine learning (ML) has made descriptor-based catalyst screening and rational design a mainstream research approach. Herein, the spectroscopic descriptors reported in recent years are highlighted in the field of catalysis. Both vibrational spectra and X-ray absorption spectra have demonstrated strong ability to predict catalytic structures and properties. Through several cases, the interpretable ML models based on spectroscopic descriptors are discussed to reveal phys. knowledge and catalytic mechanism and to exhibit superiority in transfer learning tasks and imperfect data scenarios. Finally, in this Viewpoint, we illustrate the challenges in the research field of interpretable ML models with spectroscopic descriptors and provide perspectives.
- 461Andersen, M.; Reuter, K. Adsorption Enthalpies for Catalysis Modeling through Machine-Learned Descriptors. Acc. Chem. Res. 2021, 54, 2741– 2749, DOI: 10.1021/acs.accounts.1c00153461Adsorption Enthalpies for Catalysis Modeling through Machine-Learned DescriptorsAndersen, Mie; Reuter, KarstenAccounts of Chemical Research (2021), 54 (12), 2741-2749CODEN: ACHRE4; ISSN:0001-4842. (American Chemical Society)A review. Heterogeneous catalysts are rather complex materials that come in many classes (e.g., metals, oxides, carbides) and shapes. At the same time, the interaction of the catalyst surface with even a relatively simple gas-phase environment such as syngas (CO and H2) may already produce a wide variety of reaction intermediates ranging from atoms to complex mols. The starting point for creating predictive maps of, e.g., surface coverages or chem. activities of potential catalyst materials is the reliable prediction of adsorption enthalpies of all of these intermediates. For simple systems, direct d. functional theory (DFT) calcns. are currently the method of choice. However, a wider exploration of complex materials and reaction networks generally requires enthalpy predictions at lower computational cost. The use of machine learning (ML) and related techniques to make accurate and low-cost predictions of quantum mech. calcns. has gained increasing attention lately. The employed approaches span from phys. motivated models over hybrid physics-ΔML approaches to complete black-box methods such as deep neural networks. In recent works the authors have explored the possibilities for using a compressed sensing method (Sure Independence Screening and Sparsifying Operator, SISSO) to identify sparse (low-dimensional) descriptors for the prediction of adsorption enthalpies at various active-site motifs of metals and oxides. The authors start from a set of phys. motivated primary features such as at. acid/base properties, coordination nos., or band moments and let the data and the compressed sensing method find the best algebraic combination of these features. Here the authors take this work as a starting point to categorize and compare recent ML-based approaches with a particular focus on model sparsity, data efficiency, and the level of phys. insight that 1 can obtain from the model. Looking ahead, while many works to date have focused only on the mere prediction of databases of, e.g., adsorption enthalpies, there is also an emerging interest in the field to start using ML predictions to answer fundamental science questions about the functioning of heterogeneous catalysts or perhaps even to design better catalysts than the authors know today. This task is significantly simplified in works that make use of scaling-relation-based models (volcano curves), where the model outcome is detd. by only one or 2 adsorption enthalpies and which consequently become the sole target for ML-based high-throughput screening or design. However, the availability of cheap ML energetics also allows going beyond scaling relations. From the own work in this direction, the authors will discuss the addnl. phys. insight that can be achieved by integrating ML-based predictions with traditional catalysis modeling techniques from thermal and electrocatalysis, such as the computational H electrode and microkinetic modeling, as well as the challenges that lie ahead.
- 462Restuccia, P.; Losi, G.; Chehaimi, O.; Marsili, M.; Righi, M. C. High-Throughput First-Principles Prediction of Interfacial Adhesion Energies in Metal-on-Metal Contacts. ACS Appl. Mater. Interfaces 2023, 15, 19624– 19633, DOI: 10.1021/acsami.3c00662462High-Throughput First-Principles Prediction of Interfacial Adhesion Energies in Metal-on-Metal ContactsRestuccia, Paolo; Losi, Gabriele; Chehaimi, Omar; Marsili, Margherita; Righi, M. CleliaACS Applied Materials & Interfaces (2023), 15 (15), 19624-19633CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Adhesion energy, a measure of the strength by which two surfaces bind together, ultimately dictates the mech. behavior and failure of interfaces. As natural and artificial solid interfaces are ubiquitous, adhesion energy represents a key quantity in a variety of fields ranging from geol. to nanotechnol. Because of intrinsic difficulties in the simulation of systems where two different lattices are matched, and despite their importance, no systematic, accurate first-principles detn. of heterostructure adhesion energy is available. We have developed robust, automatic high-throughput workflow able to fill this gap by systematically searching for the optimal interface geometry and accurately detg. adhesion energies. We apply it here for the first time to perform the screening of around a hundred metallic heterostructures relevant for technol. applications. This allows us to populate a database of accurate values, which can be used as input parameters for macroscopic models. Moreover, it allows us to benchmark commonly used, empirical relations that link adhesion energies to the surface energies of its constituent and to improve their predictivity employing only quantities that are easily measurable or computable.
- 463Trujillo, M. J.; Strausser, S. L.; Becca, J. C.; DeJesus, J. F.; Jensen, L.; Jenkins, D. M.; Camden, J. P. Using SERS To Understand the Binding of N-Heterocyclic Carbenes to Gold Surfaces. J. Phys. Chem. Lett. 2018, 9, 6779– 6785, DOI: 10.1021/acs.jpclett.8b02764463Using SERS To Understand the Binding of N-Heterocyclic Carbenes to Gold SurfacesTrujillo, Michael J.; Strausser, Shelby L.; Becca, Jeffrey C.; DeJesus, Joseph F.; Jensen, Lasse; Jenkins, David M.; Camden, Jon P.Journal of Physical Chemistry Letters (2018), 9 (23), 6779-6785CODEN: JPCLCD; ISSN:1948-7185. (American Chemical Society)Surface functionalization is an essential component of most applications of noble-metal surfaces. Thiols and amines are traditionally employed to attach mols. to noble-metal surfaces, but they have limitations. A growing body of research, however, suggests that N-heterocyclic carbenes (NHCs) can be readily employed for surface functionalization with superior chem. stability compared with thiols. The authors demonstrate the power of surface-enhanced Raman scattering combined with theory to present a comprehensive picture of NHC binding to Au surfaces. In particular, the authors synthesize a library of NHC isotopologues and use surface-enhanced Raman scattering to record the vibrational spectra of these NHCs while bound to Au surfaces. Exptl. data are compared with 1st-principles theory, yielding numerous new insights into the binding of NHCs to Au surfaces. In addn. to these insights, the authors expect approach to be a general method for probing the local surface properties of NHC-functionalized surfaces for their expanding use in sensing applications.
- 464Liu, X.-L.; Leng, Y.-C.; Lin, M.-L.; Cong, X.; Tan, P.-H. Signal-to-noise ratio of Raman signal measured by multichannel detectors*. Chin. Phys. B 2021, 30, 097807 DOI: 10.1088/1674-1056/ac1f06There is no corresponding record for this reference.
- 465Fang, S.; Wu, S.; Chen, Z.; He, C.; Lin, L. L.; Ye, J. Recent progress and applications of Raman spectrum denoising algorithms in chemical and biological analyses: A review. TrAC Trends in Analytical Chemistry 2024, 172, 117578, DOI: 10.1016/j.trac.2024.117578There is no corresponding record for this reference.
- 466Zhang, K.; Zuo, W.; Chen, Y.; Meng, D.; Zhang, L. Beyond a Gaussian Denoiser: Residual Learning of Deep CNN for Image Denoising. IEEE Trans. Image Process. 2017, 26, 3142– 3155, DOI: 10.1109/TIP.2017.2662206466Beyond a Gaussian Denoiser: Residual Learning of Deep CNN for Image DenoisingZhang Kai; Zuo Wangmeng; Chen Yunjin; Meng Deyu; Zhang LeiIEEE transactions on image processing : a publication of the IEEE Signal Processing Society (2017), 26 (7), 3142-3155 ISSN:.The discriminative model learning for image denoising has been recently attracting considerable attentions due to its favorable denoising performance. In this paper, we take one step forward by investigating the construction of feed-forward denoising convolutional neural networks (DnCNNs) to embrace the progress in very deep architecture, learning algorithm, and regularization method into image denoising. Specifically, residual learning and batch normalization are utilized to speed up the training process as well as boost the denoising performance. Different from the existing discriminative denoising models which usually train a specific model for additive white Gaussian noise at a certain noise level, our DnCNN model is able to handle Gaussian denoising with unknown noise level (i.e., blind Gaussian denoising). With the residual learning strategy, DnCNN implicitly removes the latent clean image in the hidden layers. This property motivates us to train a single DnCNN model to tackle with several general image denoising tasks, such as Gaussian denoising, single image super-resolution, and JPEG image deblocking. Our extensive experiments demonstrate that our DnCNN model can not only exhibit high effectiveness in several general image denoising tasks, but also be efficiently implemented by benefiting from GPU computing.
- 467Zhang, K.; Zuo, W.; Zhang, L. FFDNet: Toward a Fast and Flexible Solution for CNN-Based Image Denoising. IEEE Trans. Image Process. 2018, 27, 4608– 4622, DOI: 10.1109/TIP.2018.2839891There is no corresponding record for this reference.
- 468Tian, C.; Xu, Y.; Li, Z.; Zuo, W.; Fei, L.; Liu, H. Attention-guided CNN for image denoising. Neural Networks 2020, 124, 117– 129, DOI: 10.1016/j.neunet.2019.12.024468Attention-guided CNN for image denoisingTian Chunwei; Xu Yong; Li Zuoyong; Zuo Wangmeng; Fei Lunke; Liu HongNeural networks : the official journal of the International Neural Network Society (2020), 124 (), 117-129 ISSN:.Deep convolutional neural networks (CNNs) have attracted considerable interest in low-level computer vision. Researches are usually devoted to improving the performance via very deep CNNs. However, as the depth increases, influences of the shallow layers on deep layers are weakened. Inspired by the fact, we propose an attention-guided denoising convolutional neural network (ADNet), mainly including a sparse block (SB), a feature enhancement block (FEB), an attention block (AB) and a reconstruction block (RB) for image denoising. Specifically, the SB makes a tradeoff between performance and efficiency by using dilated and common convolutions to remove the noise. The FEB integrates global and local features information via a long path to enhance the expressive ability of the denoising model. The AB is used to finely extract the noise information hidden in the complex background, which is very effective for complex noisy images, especially real noisy images and bind denoising. Also, the FEB is integrated with the AB to improve the efficiency and reduce the complexity for training a denoising model. Finally, a RB aims to construct the clean image through the obtained noise mapping and the given noisy image. Additionally, comprehensive experiments show that the proposed ADNet performs very well in three tasks (i.e. synthetic and real noisy images, and blind denoising) in terms of both quantitative and qualitative evaluations. The code of ADNet is accessible at https://github.com/hellloxiaotian/ADNet.
- 469Dabov, K.; Foi, A.; Katkovnik, V.; Egiazarian, K. Image Denoising by Sparse 3-D Transform-Domain Collaborative Filtering. IEEE Trans. Image Process. 2007, 16, 2080– 2095, DOI: 10.1109/TIP.2007.901238There is no corresponding record for this reference.
- 470Luo, S.-h.; Wang, X.; Chen, G.-y.; Xie, Y.; Zhang, W.-h.; Zhou, Z.-f.; Zhang, Z.-m.; Ren, B.; Liu, G.-k.; Tian, Z.-q. Developing a Peak Extraction and Retention (PEER) Algorithm for Improving the Temporal Resolution of Raman Spectroscopy. Anal. Chem. 2021, 93, 8408– 8413, DOI: 10.1021/acs.analchem.0c05391470Developing a Peak Extraction and Retention (PEER) Algorithm for Improving the Temporal Resolution of Raman SpectroscopyLuo, Si-heng; Wang, Xin; Chen, Gan-yu; Xie, Yi; Zhang, Wen-han; Zhou, Zhi-fan; Zhang, Zhi-min; Ren, Bin; Liu, Guo-kun; Tian, Zhong-qunAnalytical Chemistry (Washington, DC, United States) (2021), 93 (24), 8408-8413CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)In spectroscopic anal., push-to-the-limit sensitivity is one of the important topics, particularly when facing the qual. and quant. analyses of the trace target. Normally, the effective recognition and extn. of weak signals are the first key steps, for which there has been considerable effort in developing various denoising algorithms for decades. Nevertheless, the lower the signal-to-noise ratio (SNR), the greater the deviation of the peak height and shape during the denoising process. Therefore, we propose a denoising algorithm along with peak extn. and retention (PEER). First, both the first and second derivs. of the Raman spectrum are used to det. Raman peaks with a high SNR whose peak information is kept away from the denoising process. Second, an optimized window smoothing algorithm is applied to the left part of the Raman spectrum, which is combined with the untreated Raman peaks to obtain the denoised Raman spectrum. The PEER algorithm is demonstrated with much better signal extn. and retention and successfully improves the temporal resoln. of Raman imaging of a living cell by at least 1 order of magnitude higher than those by traditional algorithms.
- 471He, H.; Cao, M.; Gao, Y.; Zheng, P.; Yan, S.; Zhong, J.-H.; Wang, L.; Jin, D.; Ren, B. Noise learning of instruments for high-contrast, high-resolution and fast hyperspectral microscopy and nanoscopy. Nat. Commun. 2024, 15, 754, DOI: 10.1038/s41467-024-44864-5There is no corresponding record for this reference.
- 472Lehtinen, J.; Munkberg, J.; Hasselgren, J.; Laine, S.; Karras, T.; Aittala, M.; Aila, T. Noise2Noise: Learning Image Restoration without Clean Data. In International Conference on Machine Learning , 2018; Vol. 80.There is no corresponding record for this reference.
- 473Wang, X.; Liu, G.; Xu, M.; Ren, B.; Tian, Z. Development of Weak Signal Recognition and an Extraction Algorithm for Raman Imaging. Anal. Chem. 2019, 91, 12909– 12916, DOI: 10.1021/acs.analchem.9b02887473Development of Weak Signal Recognition and an Extraction Algorithm for Raman ImagingWang, Xin; Liu, Guokun; Xu, Mengxi; Ren, Bin; Tian, ZhongqunAnalytical Chemistry (Washington, DC, United States) (2019), 91 (20), 12909-12916CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Improving time resoln. of Raman imaging is essential for the observation of dynamic processes involved in interfacial catalysis and biol. systems. The crucial step is how to recognize and ext. weak Raman signal overwhelmed in the strong noise under the low signal to noise ratio (SNR) condition. Here, by exploring the relationship between SNR of single Raman spectrum and SSIM (the key parameter evaluating image quality) of whole image, the authors detd. a semi-empirical threshold with SNR=0 dB for clear imaging for the first time. Therefore, the authors proposed one signal processing algorithm for fast Raman imaging by reconstructing the Raman spectrum with the aid of weak signal processing: extg. the reliable Raman signal of the target under low signal-noise ratio (SNR), and then detg. the suitable scanning time to obtain the Raman image with trustworthy image quality. In the first step, FFT, least square and 2-D median filter are sequentially applied to improve the SNR of each raw Raman spectrum. In the second step, a local SNR evaluation strategy is developed to predict image quality, as well as the detn. of clear imaging. The proposed method was successfully applied to the fast imaging of cell under low SNR condition.
- 474Tang, Q.; Hu, J.; Chen, J.; Xue, C.; Chen, J.; Dang, H.; Lu, D.; Liu, H.; Sun, Q.; Xiong, Q.; Cong, L.; Shum, P. P. A Two-stage Raman Imaging Denoising Algorithm Based on Deep Learning. In 2022 Asia Communications and Photonics Conference (ACP) , 2022; pp 2096– 2099.There is no corresponding record for this reference.
- 475Luo, S.-h.; Zhao, X.-j.; Cao, M.-f.; Xu, J.; Wang, W.-l.; Lu, X.-y.; Huang, Q.-t.; Yue, X.-x.; Liu, G.-k.; Yang, L.; Ren, B.; Tian, Z.-q. Signal2signal: Pushing the Spatiotemporal Resolution to the Limit by Single Chemical Hyperspectral Imaging. Anal. Chem. 2024, 96, 6550– 6557, DOI: 10.1021/acs.analchem.3c04609There is no corresponding record for this reference.
- 476Yu, H.; Zhao, L.; Wang, H. Image Denoising Using Trivariate Shrinkage Filter in the Wavelet Domain and Joint Bilateral Filter in the Spatial Domain. IEEE Trans. Image Process. 2009, 18, 2364– 2369, DOI: 10.1109/TIP.2009.2026685There is no corresponding record for this reference.
- 477Goyal, B.; Dogra, A.; Agrawal, S.; Sohi, B. S.; Sharma, A. Image denoising review: From classical to state-of-the-art approaches. Information Fusion 2020, 55, 220– 244, DOI: 10.1016/j.inffus.2019.09.003There is no corresponding record for this reference.
- 478Voulodimos, A.; Doulamis, N.; Doulamis, A.; Protopapadakis, E. Deep Learning for Computer Vision: A Brief Review. Comput. Intell. Neurosci. 2018, 2018, 7068349, DOI: 10.1155/2018/7068349478Deep Learning for Computer Vision: A Brief ReviewVoulodimos Athanasios; Voulodimos Athanasios; Doulamis Nikolaos; Doulamis Anastasios; Protopapadakis EftychiosComputational intelligence and neuroscience (2018), 2018 (), 7068349 ISSN:.Over the last years deep learning methods have been shown to outperform previous state-of-the-art machine learning techniques in several fields, with computer vision being one of the most prominent cases. This review paper provides a brief overview of some of the most significant deep learning schemes used in computer vision problems, that is, Convolutional Neural Networks, Deep Boltzmann Machines and Deep Belief Networks, and Stacked Denoising Autoencoders. A brief account of their history, structure, advantages, and limitations is given, followed by a description of their applications in various computer vision tasks, such as object detection, face recognition, action and activity recognition, and human pose estimation. Finally, a brief overview is given of future directions in designing deep learning schemes for computer vision problems and the challenges involved therein.
- 479Tian, C.; Fei, L.; Zheng, W.; Xu, Y.; Zuo, W.; Lin, C.-W. Deep learning on image denoising: An overview. Neural Networks 2020, 131, 251– 275, DOI: 10.1016/j.neunet.2020.07.025479Deep learning on image denoising: An overviewTian Chunwei; Fei Lunke; Zheng Wenxian; Xu Yong; Zuo Wangmeng; Lin Chia-WenNeural networks : the official journal of the International Neural Network Society (2020), 131 (), 251-275 ISSN:.Deep learning techniques have received much attention in the area of image denoising. However, there are substantial differences in the various types of deep learning methods dealing with image denoising. Specifically, discriminative learning based on deep learning can ably address the issue of Gaussian noise. Optimization models based on deep learning are effective in estimating the real noise. However, there has thus far been little related research to summarize the different deep learning techniques for image denoising. In this paper, we offer a comparative study of deep techniques in image denoising. We first classify the deep convolutional neural networks (CNNs) for additive white noisy images; the deep CNNs for real noisy images; the deep CNNs for blind denoising and the deep CNNs for hybrid noisy images, which represents the combination of noisy, blurred and low-resolution images. Then, we analyze the motivations and principles of the different types of deep learning methods. Next, we compare the state-of-the-art methods on public denoising datasets in terms of quantitative and qualitative analyses. Finally, we point out some potential challenges and directions of future research.
- 480Horgan, C. C.; Jensen, M.; Nagelkerke, A.; St-Pierre, J.-P.; Vercauteren, T.; Stevens, M. M.; Bergholt, M. S. High-Throughput Molecular Imaging via Deep-Learning-Enabled Raman Spectroscopy. Anal. Chem. 2021, 93, 15850– 15860, DOI: 10.1021/acs.analchem.1c02178480High-Throughput Molecular Imaging via Deep-Learning-Enabled Raman SpectroscopyHorgan, Conor C.; Jensen, Magnus; Nagelkerke, Anika; St-Pierre, Jean-Philippe; Vercauteren, Tom; Stevens, Molly M.; Bergholt, Mads S.Analytical Chemistry (Washington, DC, United States) (2021), 93 (48), 15850-15860CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Raman spectroscopy enables nondestructive, label-free imaging with unprecedented mol. contrast, but is limited by slow data acquisition, largely preventing high-throughput imaging applications. Here, we present a comprehensive framework for higher-throughput mol. imaging via deep-learning-enabled Raman spectroscopy, termed DeepeR, trained on a large data set of hyperspectral Raman images, with over 1.5 million spectra (400 h of acquisition) in total. We first perform denoising and reconstruction of low signal-to-noise ratio Raman mol. signatures via deep learning, with a 10x improvement in the mean-squared error over common Raman filtering methods. Next, we develop a neural network for robust 2-4x spatial super-resoln. of hyperspectral Raman images that preserve mol. cellular information. Combining these approaches, we achieve Raman imaging speed-ups of up to 40-90x, enabling good-quality cellular imaging with a high-resoln., high signal-to-noise ratio in under 1 min. We further demonstrate Raman imaging speed-up of 160x, useful for lower resoln. imaging applications such as the rapid screening of large areas or for spectral pathol. Finally, transfer learning is applied to extend DeepeR from cell to tissue-scale imaging. DeepeR provides a foundation that will enable a host of higher-throughput Raman spectroscopy and mol. imaging applications across biomedicine.
- 481Hu, J.; Chen, G. J.; Xue, C.; Liang, P.; Xiang, Y.; Zhang, C.; Chi, X.; Liu, G.; Ye, Y.; Cui, D.; Zhang, D.; yu, X.; Dang, H.; Zhang, W.; Chen, J.; Tang, Q.; Guo, P.; Ho, H.-P.; Li, Y.; Cong, L.; Shum, P. P. RSPSSL: A novel high-fidelity Raman spectral preprocessing scheme to enhance biomedical applications and chemical resolution visualization. Light Sci. Appl. 2024, 13, 52, DOI: 10.1038/s41377-024-01394-5There is no corresponding record for this reference.
- 482Luo, S.-H.; Pan, S.-Q.; Chen, G.-Y.; Xie, Y.; Ren, B.; Liu, G.-K.; Tian, Z.-Q. Revealing the Denoising Principle of Zero-Shot N2N-Based Algorithm from 1D Spectrum to 2D Image. Anal. Chem. 2024, 96, 4086– 4092, DOI: 10.1021/acs.analchem.3c04608There is no corresponding record for this reference.
- 483Drumetz, L.; Chanussot, J.; Jutten, C. Variability of the endmembers in spectral unmixing. In Data Handling in Science and Technology; Elsevier: 2019; pp 167– 203.There is no corresponding record for this reference.
- 484Schmidt, R. W.; Ariese, F.; Omidikia, N. A comparison of multivariate curve resolution with endmember extraction methods in hyperspectral Raman imaging. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 2024, 323, 124868, DOI: 10.1016/j.saa.2024.124868There is no corresponding record for this reference.
- 485Olmos, V.; Benitez, L.; Marro, M.; Loza-Alvarez, P.; Pina, B.; Tauler, R.; De Juan, A. Relevant aspects of unmixing/resolution analysis for the interpretation of biological vibrational hyperspectral images. TrAC Trends in Analytical Chemistry 2017, 94, 130– 140, DOI: 10.1016/j.trac.2017.07.004There is no corresponding record for this reference.
- 486Su, X.; Xie, Y.; Liu, X.; Chen, M.; Zheng, C.; Zhong, H.; Li, M. Absolute quantification of serum exosomes in patients with an sers-lateral flow strip biosensor for noninvasive clinical cancer diagnosis. ACS Appl. Mater. Interfaces 2023, 15, 37130– 37142, DOI: 10.1021/acsami.3c05039There is no corresponding record for this reference.
- 487Haessler, A.; Jung, N.; Windbergs, M. Unraveling Molecular Composition in Biological Samples–Systematic Evaluation of Statistical Methods for the Analysis of Hyperspectral Raman Data. Anal. Chem. 2023, 95, 17646– 17653, DOI: 10.1021/acs.analchem.3c03368There is no corresponding record for this reference.
- 488Zhang, Y.; Ye, Z.; Li, C.; Chen, Q.; Aljuhani, W.; Huang, Y.; Xu, X.; Wu, C.; Bell, S. E.; Xu, Y. General approach to surface-accessible plasmonic Pickering emulsions for SERS sensing and interfacial catalysis. Nat. Commun. 2023, 14, 1392, DOI: 10.1038/s41467-023-37001-1488General approach to surface-accessible plasmonic Pickering emulsions for SERS sensing and interfacial catalysisZhang, Yingrui; Ye, Ziwei; Li, Chunchun; Chen, Qinglu; Aljuhani, Wafaa; Huang, Yiming; Xu, Xin; Wu, Chunfei; Bell, Steven E. J.; Xu, YikaiNature Communications (2023), 14 (1), 1392CODEN: NCAOBW; ISSN:2041-1723. (Nature Portfolio)Pickering emulsions represent an important class of functional materials with potential applications in sustainability and healthcare. Currently, the synthesis of Pickering emulsions relies heavily on the use of strongly adsorbing mol. modifiers to tune the surface chem. of the nanoparticle constituents. This approach is inconvenient and potentially a dead-end for many applications since the adsorbed modifiers prevent interactions between the functional nanosurface and its surroundings. Here, we demonstrate a general modifier-free approach to construct Pickering emulsions by using a combination of stabilizer particles, which stabilize the emulsion droplet, and a second population of unmodified functional particles that sit alongside the stabilizers at the interface. Freeing Pickering emulsions from chem. modifiers unlocks their potential across a range of applications including plasmonic sensing and interfacial catalysis that have previously been challenging to achieve. More broadly, this strategy provides an approach to the development of surface-accessible nanomaterials with enhanced and/or addnl. properties from a wide range of nano-building blocks including org. nanocrystals, carbonaceous materials, metals and oxides.
- 489Masango, S. S.; Hackler, R. A.; Large, N.; Henry, A.-I.; McAnally, M. O.; Schatz, G. C.; Stair, P. C.; Van Duyne, R. P. High-resolution distance dependence study of surface-enhanced Raman scattering enabled by atomic layer deposition. Nano Lett. 2016, 16, 4251– 4259, DOI: 10.1021/acs.nanolett.6b01276489High-Resolution Distance Dependence Study of Surface-Enhanced Raman Scattering Enabled by Atomic Layer DepositionMasango, Sicelo S.; Hackler, Ryan A.; Large, Nicolas; Henry, Anne-Isabelle; McAnally, Michael O.; Schatz, George C.; Stair, Peter C.; Van Duyne, Richard P.Nano Letters (2016), 16 (7), 4251-4259CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)The authors present a high-resoln. distance dependence study of surface-enhanced Raman scattering (SERS) enabled by at. layer deposition (ALD) at 55 and 100°. ALD is used to deposit monolayers of Al2O3 on bare Ag film over nanospheres (AgFONs) and AgFONs functionalized with self-assembled monolayers. Operando SERS is used to measure the intensities of the Al-Me and C-H stretches from trimethylaluminum (TMA) as a function of distance from the AgFON surface. This study clearly demonstrates that SERS on AgFON substrates displays both a short- and long-range nm scale distance dependence. Agreement is obtained between these expts. and theory that incorporates both short-range and long-range terms. This is a high-resoln. operando SERS distance dependence study performed in 1 integrated expt. using ALD Al2O3 as the spacer layer and Raman label simultaneously. The long-range SERS distance dependence should make it possible to detect chemisorbed surface species located as far as ∼3 nm from the AgFON substrate and will provide new insight into the surface chem. of ALD and catalytic reactions.
- 490Bell, S. E.; Charron, G.; Cortés, E.; Kneipp, J.; de la Chapelle, M. L.; Langer, J.; Procházka, M.; Tran, V.; Schlücker, S. Towards reliable and quantitative surface-enhanced Raman scattering (SERS): from key parameters to good analytical practice. Angew. Chem., Int. Ed. 2020, 59, 5454– 5462, DOI: 10.1002/anie.201908154490Towards Reliable and Quantitative Surface-Enhanced Raman Scattering (SERS): From Key Parameters to Good Analytical PracticeBell, Steven E. J.; Charron, Gaelle; Cortes, Emiliano; Kneipp, Janina; de la Chapelle, Marc Lamy; Langer, Judith; Prochazka, Marek; Tran, Vi; Schluecker, SebastianAngewandte Chemie, International Edition (2020), 59 (14), 5454-5462CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. Exptl. results obtained in different labs. world-wide by researchers using surface-enhanced Raman scattering (SERS) can differ significantly. The authors, an international team of scientists with long-standing expertise in SERS, address this issue from the perspective by presenting considerations on reliable and quant. SERS. The central idea of this joint effort is to highlight key parameters and pitfalls that are often encountered in the literature. To that end, the authors provide here recommendations on: (a) the characterization of solid and colloidal SERS substrates by correlative electron and optical microscopy and spectroscopy, (b) the detn. of the SERS enhancement factor, including suitable Raman reporter/probe mols., and (c) good anal. practice. Hopefully newcomers and specialists will benefit from these recommendations to increase the inter-lab. comparability of exptl. SERS results and further establish SERS as an anal. tool.
- 491Villa, J. E. L.; Pasquini, C.; Poppi, R. J. Surface-enhanced Raman spectroscopy and MCR-ALS for the selective sensing of urinary adenosine on filter paper. Talanta 2018, 187, 99– 105, DOI: 10.1016/j.talanta.2018.05.022491Surface-enhanced Raman spectroscopy and MCR-ALS for the selective sensing of urinary adenosine on filter paperVilla, Javier E. L.; Pasquini, Celio; Poppi, Ronei J.Talanta (2018), 187 (), 99-105CODEN: TLNTA2; ISSN:0039-9140. (Elsevier B.V.)Adenosine is a purine nucleoside that is present in all human cells and is essential for regulating certain physiol. activities in tissues and organs. Since adenosine is considered to be a potential cancer biomarker in urine, its detn. may be crucial for the early diagnosis and non-invasive monitoring of cancer. Herein, we present a label-free method to quantify urinary adenosine using surface-enhanced Raman spectroscopy (SERS) and multivariate curve resoln.-alternating least squares (MCR-ALS). Ring-oven preconcn. and direct deposition of monodisperse gold nanoparticles on filter paper were employed to improve the sampling efficiency. Further, MCR-ALS (assessed with and without a correlation constraint), the std. addn. method and pH controls were combined to compensate for the matrix effect and to address overlapping bands in the anal. of human urine samples. As a result, the proposed method showed to be sensitive (LOD varying between 3.8 and 4.9 μmol L-1, S/R = 3), reproducible (RSD less than ± 15%), and selective over other nucleosides (guanosine, cytidine, thymidine and uridine) and unknown interferences (second-order advantage). This is the first report of a SERS-chemometric method applied to urinary adenosine sensing at physiol. relevant concns., with minimal sample prepn., and has strong potential to be a valuable tool in cancer research.
- 492He, J.; Abdel-Galeil, M. M.; Nemoto, M.; Kishimoto, N.; Morita, S.-i. Bio-Raman non-negative matrix factorization: its practical methodology. Applied Physics Express 2023, 16, 026502 DOI: 10.35848/1882-0786/acb6ceThere is no corresponding record for this reference.
- 493Deng, X.; Milligan, K.; Ali-Adeeb, R.; Shreeves, P.; Brolo, A.; Lum, J. J.; Andrews, J. L.; Jirasek, A. Group and basis restricted non-negative matrix factorization and random forest for molecular histotype classification and Raman biomarker monitoring in breast cancer. Applied spectroscopy 2022, 76, 462– 474, DOI: 10.1177/00037028211035398There is no corresponding record for this reference.
- 494Lobanova, E.; Lobanov, S. Efficient quantitative hyperspectral image unmixing method for large-scale Raman micro-spectroscopy data analysis. Anal. Chim. Acta 2019, 1050, 32– 43, DOI: 10.1016/j.aca.2018.11.018494Efficient quantitative hyperspectral image unmixing method for large-scale Raman micro-spectroscopy data analysisLobanova, E. G.; Lobanov, S. V.Analytica Chimica Acta (2019), 1050 (), 32-43CODEN: ACACAM; ISSN:0003-2670. (Elsevier B.V.)Vibrational micro-spectroscopy is a powerful optical tool, providing a non-invasive label-free chem. specific imaging for many chem. and biomedical applications. However, hyperspectral image produced by Raman micro-spectroscopy typically consists of thousands discrete pixel points, each having individual Raman spectrum at thousand wavenumbers, and therefore requires appropriate image unmixing computational methods to retrieve non-neg. spatial concn. and corresponding non-neg. spectra of the image biochem. constituents. Here, we present a new efficient Quant. Hyperspectral Image Unmixing (Q-HIU) method for large-scale Raman micro-spectroscopy data anal. This method enables to simultaneously analyze multi-set Raman hyperspectral images in three steps: (i) Singular Value Decompn. with innovative Automatic Divisive Correlation which autonomously filters spatially and spectrally uncorrelated noise from data; (ii) a robust subtraction of fluorescent background from the data using a newly developed algorithm called Bottom Gaussian Fitting; (iii) an efficient Quant. Unsupervised/Partially Supervised Non-neg. Matrix Factorization method, which rigorously retrieves non-neg. spatial concn. maps and spectral profiles of the samples' biochem. constituents with no a priori information or when one or several samples' constituents are known. As compared with state-of-the-art methods, our approach allows to achieve significantly more accurate results and efficient quantification with several orders of magnitude shorter computational time as verified on both artificial and real exptl. data. We apply Q-HIU to the anal. of large-scale Raman hyperspectral images of human atherosclerotic aortic tissues and our results show a proof-of-principle for the proposed method to retrieve and quantify the biochem. compn. of the tissues, consisting of both high and low concd. compds. Along with the established hallmarks of atherosclerosis including cholesterol/cholesterol ester, triglyceride and calcium hydroxyapatite crystals, our Q-HIU allowed to identify the significant accumulations of oxidatively modified lipids co-localizing with the atherosclerotic plaque lesions in the aortic tissues, possibly reflecting the persistent presence of inflammation and oxidative damage in these regions, which are in turn able to promote the disease pathol. For minor chem. components in the diseased tissues, our Q-HIU was able to detect the signatures of calcium hydroxyapatite and β-carotene with relative mean Raman concns. as low as 0.09% and 0.04% from the original Raman intensity matrix with noise and fluorescent background contributions of 3% and 94%, resp.
- 495Kneipp, J.; Kneipp, K. Surface Enhanced Nonlinear Raman Processes for Advanced Vibrational Probing. ACS Nano 2024, 18, 20851– 20860, DOI: 10.1021/acsnano.4c07508There is no corresponding record for this reference.
- 496Zhao, F.; Zheng, Y.; Zhao, Z.; Wang, W.; Xu, T.; Xue, X.; Fu, W.; Ling, Y.; Shi, J.; Zhang, Z. Re-understanding of SERS for General and Standardized Quantitative Analysis. Nano Lett. 2024, 24, 10290, DOI: 10.1021/acs.nanolett.4c02789There is no corresponding record for this reference.
- 497Xu, Y.; Aljuhani, W.; Zhang, Y.; Ye, Z.; Li, C.; Bell, S. E. J. A practical approach to quantitative analytical surface-enhanced Raman spectroscopy. Chem. Soc. Rev. 2025, 54, 62– 84, DOI: 10.1039/D4CS00861HThere is no corresponding record for this reference.
- 498Su, M.; Wang, C.; Wang, T.; Jiang, Y.; Xu, Y.; Liu, H. Breaking the affinity limit with dual-phase-accessible hotspot for ultrahigh Raman scattering of nonadsorptive molecules. Anal. Chem. 2020, 92, 6941– 6948, DOI: 10.1021/acs.analchem.9b05727498Breaking the Affinity Limit with Dual-Phase-Accessible Hotspot for Ultrahigh Raman Scattering of Nonadsorptive MoleculesSu, Mengke; Wang, Chao; Wang, Tengfei; Jiang, Yifan; Xu, Yue; Liu, HonglinAnalytical Chemistry (Washington, DC, United States) (2020), 92 (10), 6941-6948CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)For surface-enhanced Raman scattering (SERS) anal., only analytes that can be absorbed spontaneously onto a noble metal surface can be detected effectively. Therefore, getting nonadsorptive mols. close enough to the surface has always been a key challenge in SERS anal. Here absorbance measurements show that the liq.-interfacial array (LIA) does not adsorb or enrich benzopyrene (Bap) mols., which lack effective functional groups that can interact with the noble metal surfaces. But the SERS intensity of 0.1 ppm Bap on the LIA is 10 times larger than that of 10 ppm Bap on traditional solid substrate, i.e., 3 orders of magnitude of enhancement. The LIA overcomes the restriction of affinity between Bap mols. and the metal surface, and the Bap mols. can easily enter nanogaps without steric hindrance. Furthermore, both adsorptive and nonadsorptive mols. were used to observe the SERS enhancement behavior on the LIA platforms. In multiple detection, competitive SERS signal changes could be obsd. between adsorptive and nonadsorptive mols. or between nonadsorptive and nonadsorptive mols. A theor. scheme was profiled for localized surface plasmon resonance (SPR) properties of the LIA. Finite difference-time domain (FDTD) simulation shows that the LIAs have biphasic and accessible asym. hotspots, and the elec. field enhancement in the CHCl3 (O) phase is approx. four times larger than that of the water (W) phase. In addn., the position and relative strength of the electromagnetic field depend on the spatial position of gold nanoparticles (GNPs) relative to the liq.-liq. interface (LLI), i.e., when the GNP dimer is completely immersed in a certain phase, the electromagnetic field enhancement of the CHCl3 phase is approx. 7 times larger than that of the W phase. We speculate that dual-phase-accessible hotspots and the hydrophobic environment provided by CHCl3 are two important factors contributing to successful detection of four common polycyclic arom. hydrocarbons (PAHs) with a detection limit of 10 ppb. Finally, the LIA platform successfully realizes simultaneous detection of multiple PAHs in both plant and animal oils with good stability. This study provides a new direction for the development of high-efficiency and practical SERS technol. for nonadsorptive mols.
- 499Morton, S. M.; Jensen, L. Understanding the molecule– surface chemical coupling in SERS. J. Am. Chem. Soc. 2009, 131, 4090– 4098, DOI: 10.1021/ja809143c499Understanding the Molecule-Surface Chemical Coupling in SERSMorton, Seth M.; Jensen, LasseJournal of the American Chemical Society (2009), 131 (11), 4090-4098CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)The enhancement mechanism due to the mol.-surface chem. coupling in surface-enhanced Raman scattering (SERS) was characterized using time-dependent d. functional theory. This was achieved with a systematical study of the chem. enhancement of meta- and para-substituted pyridines interacting with a small silver cluster (Ag20). Changing the functional groups on pyridine enabled one to modulate the direct chem. interactions between the pyridine ring and the metal cluster. Surprisingly, the enhancement does not increase as more charge is transferred from the pyridine ring to the cluster. Instead, the magnitude of chem. enhancement is governed to a large extent by the energy difference between the highest occupied energy level (HOMO) of the metal and the lowest unoccupied energy level (LUMO) of the mol. The enhancement scales roughly as (ωX/‾ωe)4, where ‾ωe is an av. excitation energy between the HOMO of the metal and the LUMO of the mol. and ωX is the HOMO-LUMO gap of the free mol. The trend was verified by considering substituted benzenethiols, small mols., and silver clusters of varying sizes. The results imply that mols. that show significant stabilization of the HOMO-LUMO gaps (such as those that readily accept π-backbonding) would be likely to have strong chem. enhancement. The findings presented here provide the framework for designing new mols. which exhibit high chem. enhancements. However, it remains a challenge to accurately describe the magnitude of the Raman enhancements using electronic structure methods, esp. d. functional theory, because they often underestimate the energy gap.
- 500Su, Y.-Q.; Liu, J.; Huang, R.; Yang, H.-T.; Li, M.-X.; Pang, R.; Zhang, M.; Yang, M.-H.; Su, H.-F.; Devasenathipathy, R.; Wu, Y.-F.; Zhou, J.-Z.; Wu, D.-Y.; Xie, S.-Y.; Mao, B.-W.; Tian, Z.-Q. Plasmon-Mediated Photoelectrochemical Hot-Hole Oxidation Coupling Reactions of Adenine on Nanostructured Silver Electrodes. J. Phys. Chem. Lett. 2023, 14, 5163– 5171, DOI: 10.1021/acs.jpclett.3c00619500Plasmon-Mediated Photoelectrochemical Hot-Hole Oxidation Coupling Reactions of Adenine on Nanostructured Silver ElectrodesSu, Ya-Qiong; Liu, Jia; Huang, Rong; Yang, Hong-Tao; Li, Ming-Xue; Pang, Ran; Zhang, Meng; Yang, Meng-Han; Su, Hai-Feng; Devasenathipathy, Rajkumar; Wu, Yuan-Fei; Zhou, Jian-Zhang; Wu, De-Yin; Xie, Su-Yuan; Mao, Bing-Wei; Tian, Zhong-QunJournal of Physical Chemistry Letters (2023), 14 (22), 5163-5171CODEN: JPCLCD; ISSN:1948-7185. (American Chemical Society)Surface-enhanced Raman spectroscopy (SERS) has been widely applied in the identification and characterization of DNA structures with high efficiency. Esp., the SERS signals of the adenine group have exhibited high detection sensitivity in several biomol. systems. However, there is still no unanimous conclusion regarding the interpretation of some special kinds of SERS signals of adenine and its derivs. on silver colloids and electrodes. This Letter presents a new photochem. azo coupling reaction for adenyl residues, in which the adenine is selectively oxidized to (E)-1,2-di(7H-purin-6-yl) diazene (azopurine) in the presence of silver ions, silver colloids, and electrodes of nanostructures under visible light irradn. The product, azopurine, is first found to be responsible for the SERS signals. This photoelectrochem. oxidative coupling reaction of adenine and its derivs. is promoted by plasmon-mediated hot holes and is regulated by pos. potentials and pH of solns., which opens up new avenues for studying azo coupling in the photoelectrochem. of adenine-contg. biomols. on electrode surfaces of plasmonic metal nanostructures.
- 501Cabalo, J.; Guicheteau, J. A.; Christesen, S. Toward understanding the influence of intermolecular interactions and molecular orientation on the chemical enhancement of SERS. J. Phys. Chem. A 2013, 117, 9028– 9038, DOI: 10.1021/jp403458k501Toward Understanding the Influence of Intermolecular Interactions and Molecular Orientation on the Chemical Enhancement of SERSCabalo, Jerry; Guicheteau, Jason A.; Christesen, StevenJournal of Physical Chemistry A (2013), 117 (37), 9028-9038CODEN: JPCAFH; ISSN:1089-5639. (American Chemical Society)Implementation of SERS as an anal. technique is limited because the factors that govern the enhancement of individual vibrational modes are not well understood. Although the chem. effect only accounts for up to 2 orders of magnitude enhancement, it can still have a significant impact on the consistency of chem. spectral signatures. The authors report on a combined theor. and exptl. study on the benzenethiol on Ag and 4-mercaptophenol on Ag systems. The primary and unique finding was that for the benzenethiol on Ag system the inclusion of interaction between multiple benzenethiol analyte mols. was essential to account for the relative enhancements obsd. exptl. An examn. of the MOs showed sharing of electron d. across the entire model of multiple benzenethiol mols. mediated by the metal atoms. The addn. of multiple 4-mercaptophenol mols. to the theor. model had little effect on the predicted spectra, and the authors attribute this to the fact that a much larger model is necessary to replicate the networks of H bonds. Mol. orientation was also found to affect the predicted spectra, and an upright position improved agreement between theor. and exptl. spectra. An anal. of the vibrational frequency shifts between the normal Raman spectrum of the neat compd. and the SERS spectrum also suggests that both benzenethiol and 4-mercaptophenol are in an upright position.
- 502Burzynski, N.; Yuan, Y.; Felsen, A.; Reitano, D.; Wang, Z.; Sethi, K. A.; Lu, F.; Chiu, K. In Deep learning techniques for unmixing of hyperspectral stimulated raman scattering images. In 2021 IEEE International Conference on Big Data (Big Data) , 2021; pp 5862– 5864.There is no corresponding record for this reference.
- 503Qu, Y.; Qi, H. uDAS: An untied denoising autoencoder with sparsity for spectral unmixing. IEEE Transactions on Geoscience and Remote Sensing 2019, 57, 1698– 1712, DOI: 10.1109/TGRS.2018.2868690There is no corresponding record for this reference.
- 504Georgiev, D.; Fernandez-Galiana, A.; Vilms Pedersen, S.; Papadopoulos, G.; Xie, R.; Stevens, M. M.; Barahona, M. Hyperspectral unmixing for Raman spectroscopy via physics-constrained autoencoders. arXiv Preprint , arXiv:2403.04526, 2024. DOI: 10.1073/pnas.2407439121There is no corresponding record for this reference.
- 505Su, Y.; Li, J.; Plaza, A.; Marinoni, A.; Gamba, P.; Chakravortty, S. DAEN: Deep autoencoder networks for hyperspectral unmixing. IEEE Transactions on Geoscience and Remote Sensing 2019, 57, 4309– 4321, DOI: 10.1109/TGRS.2018.2890633There is no corresponding record for this reference.
- 506Zhang, X.; Sun, Y.; Zhang, J.; Wu, P.; Jiao, L. Hyperspectral unmixing via deep convolutional neural networks. IEEE Geoscience and Remote Sensing Letters 2018, 15, 1755– 1759, DOI: 10.1109/LGRS.2018.2857804There is no corresponding record for this reference.
- 507Hong, D.; Gao, L.; Yao, J.; Yokoya, N.; Chanussot, J.; Heiden, U.; Zhang, B. Endmember-guided unmixing network (EGU-Net): A general deep learning framework for self-supervised hyperspectral unmixing. IEEE Transactions on Neural Networks and Learning Systems 2022, 33, 6518– 6531, DOI: 10.1109/TNNLS.2021.3082289There is no corresponding record for this reference.
- 508Ghosh, P.; Roy, S. K.; Koirala, B.; Rasti, B.; Scheunders, P. Hyperspectral unmixing using transformer network. IEEE Transactions on Geoscience and Remote Sensing 2022, 60, 1– 16, DOI: 10.1109/TGRS.2022.3196057There is no corresponding record for this reference.
- 509Shahid, K. T.; Schizas, I. D. Unsupervised hyperspectral unmixing via nonlinear autoencoders. IEEE Transactions on Geoscience and Remote Sensing 2022, 60, 1– 13, DOI: 10.1109/TGRS.2021.3077833There is no corresponding record for this reference.
- 510Bai, S.; Serien, D.; Ma, Y.; Obata, K.; Sugioka, K. Attomolar Sensing Based on Liquid Interface-Assisted Surface-Enhanced Raman Scattering in Microfluidic Chip by Femtosecond Laser Processing. ACS Appl. Mater. Interfaces 2020, 12, 42328– 42338, DOI: 10.1021/acsami.0c11322510Attomolar Sensing Based on Liquid Interface-Assisted Surface-Enhanced Raman Scattering in Microfluidic Chip by Femtosecond Laser ProcessingBai, Shi; Serien, Daniela; Ma, Ying; Obata, Kotaro; Sugioka, KojiACS Applied Materials & Interfaces (2020), 12 (37), 42328-42338CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Surface-enhanced Raman scattering (SERS) is a multidisciplinary trace anal. technique based on plasmonic effects. The development of SERS microfluidic chips has been exploited extensively in recent times impacting on applications in diverse fields. However, despite much progress, the excitation of label-free mols. is extremely challenging when analyte concns. are <1 nM because of the blinking SERS effect. A novel anal. strategy which can achieve detection limits at an attomolar level is proposed. This performance improvement is due to the use of a glass microfluidic chip that features an analyte air-soln. interface which forms on the SERS substrate in the microfluidic channel, whereby the analyte mols. aggregate locally at the interface during the measurement, hence the term liq. interface-assisted SERS (LI-SERS). The microfluidic chips are fabricated using hybrid femtosecond (fs) laser processing consisting of fs laser-assisted chem. etching, selective metalization, and metal surface nanostructuring. The novel LI-SERS technique can achieve an anal. enhancement factor of 1.5 × 1014, providing a detection limit <10-17 M (<10 aM). The mechanism for the extraordinary enhancement afforded by LI-SERS is attributed to Marangoni convection induced by the photothermal effect.
- 511Hao, Q.; Li, M.; Wang, J.; Fan, X.; Jiang, J.; Wang, X.; Zhu, M.; Qiu, T.; Ma, L.; Chu, P. K.; Schmidt, O. G. Flexible Surface-Enhanced Raman Scattering Chip: A Universal Platform for Real-Time Interfacial Molecular Analysis with Femtomolar Sensitivity. ACS Appl. Mater. Interfaces 2020, 12, 54174– 54180, DOI: 10.1021/acsami.0c16315511Flexible Surface-Enhanced Raman Scattering Chip: A Universal Platform for Real-Time Interfacial Molecular Analysis with Femtomolar SensitivityHao, Qi; Li, Mingze; Wang, Jiawei; Fan, Xingce; Jiang, Jie; Wang, Xiaoxia; Zhu, Minshen; Qiu, Teng; Ma, Libo; Chu, Paul K.; Schmidt, Oliver G.ACS Applied Materials & Interfaces (2020), 12 (48), 54174-54180CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)We propose and demonstrate a flexible surface-enhanced Raman scattering (SERS) chip as a versatile platform for femtomolar detection and real-time interfacial mol. anal. The flexible SERS chip is composed of a flexible and transparent membrane and embedded plasmonic dimers with ultrahigh particle d. and ultrasmall dimer gap. The chip enables rapid identification for residuals on solid substrates with irregular surfaces or dissolved analytes in aq. soln. The sensitivity for liq.-state measurement is down to 0.06 mol. per dimers for 10-14 mol·L-1 Rhodamine 6G mol. without mol. enrichment. Strong signal fluctuation and blinking are obsd. at this concn., indicating that the detection limit is close to the single-mol. level. Meanwhile, the homogeneous liq. environment facilities accurate SERS quantification of analytes with a wide dynamic range. The synergy of flexibility and liq.-state measurement opens up avenues for the real-time study of chem. reactions. The redn. from p-nitrothiophenol (PNTP) to p-aminothiophenol (PATP) in the absence of the chem. reducing agents is obsd. at liq. interfaces by in situ SERS measurements, and the plasmon-induced hot electron is demonstrated to drive the catalytic reaction. We believe this robust and feasible approach is promising in extending the SERS technique as a general method for identifying interfacial mol. traces, tracking the evolution of heterogeneous reactions, elucidating the reaction mechanisms, and evaluating the environmental effects such as pH value and salty ions in SERS.
- 512Bhavya, M. B.; Prabhu, B. R.; Shenoy, B. M.; Bhol, P.; Swain, S.; Saxena, M.; John, N. S.; Hegde, G.; Samal, A. K. Femtomolar detection of thiram via SERS using silver nanocubes as an efficient substrate. Environmental Science: Nano 2020, 7, 3999– 4009, DOI: 10.1039/D0EN01049AThere is no corresponding record for this reference.
- 513Yu, Y.; Xiao, T.-H.; Wu, Y.; Li, W.; Zeng, Q.-G.; Long, L.; Li, Z.-Y. Roadmap for single-molecule surface-enhanced Raman spectroscopy. Advanced Photonics 2020, 2, 014002 DOI: 10.1117/1.AP.2.1.014002513Roadmap for single-molecule surface-enhanced Raman spectroscopyYu, Yang; Xiao, Ting-Hui; Wu, Yunzhao; Li, Wanjun; Zeng, Qing-Guang; Long, Li; Li, Zhi-YuanAdvanced Photonics (2020), 2 (1), 014002CODEN: APDHC9; ISSN:2577-5421. (Society of Photo-Optical Instrumentation Engineers)In the near future, single-mol. surface-enhanced Raman spectroscopy (SERS) is expected to expand the family of popular anal. tools for single-mol. characterization. We provide a roadmap for achieving single mol. SERS through different enhancement strategies for diverse applications. We introduce some characteristic features related to single-mol. SERS, such as Raman enhancement factor, intensity fluctuation, and data anal. We then review recent strategies for enhancing the Raman signal intensities of single mols., including electromagnetic enhancement, chem. enhancement, and resonance enhancement strategies. To demonstrate the utility of single-mol. SERS in practical applications, we present several examples of its use in various fields, including catalysis, imaging, and nanoelectronics. Finally, we specify current challenges in the development of single-mol. SERS and propose corresponding solns.
- 514Qian, X. M.; Nie, S. M. Single-molecule and single-nanoparticle SERS: from fundamental mechanisms to biomedical applications. Chem. Soc. Rev. 2008, 37, 912– 920, DOI: 10.1039/b708839f514Single-molecule and single-nanoparticle SERS: from fundamental mechanisms to biomedical applicationsQian, X.-M.; Nie, S. M.Chemical Society Reviews (2008), 37 (5), 912-920CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)This tutorial review discusses a new class of colloidal metal nanoparticles that is able to enhance the efficiencies of surface-enhanced Raman scattering (SERS) by as much as 1014-1015 fold. This enormous enhancement allows spectroscopic detection and identification of single mols. located on the nanoparticle surface or at the junction of two particles under ambient conditions. Considerable progress has been made in understanding the enhancement mechanisms, including definitive evidence for the single-mol. origin of fluctuating SERS signals. For applications, SERS nanoparticle tags have been developed based on the use of embedded reporter mols. and a silica or polymer encapsulation layer. The SERS nanoparticle tags are capable of providing detailed spectroscopic information and are much brighter than semiconductor quantum dots in the near-IR spectral window. These properties have raised new opportunities for multiplexed mol. diagnosis and in vivo Raman spectroscopy and imaging.
- 515Le Ru, E. C.; Meyer, M.; Etchegoin, P. G. Proof of Single-Molecule Sensitivity in Surface Enhanced Raman Scattering (SERS) by Means of a Two-Analyte Technique. J. Phys. Chem. B 2006, 110, 1944– 1948, DOI: 10.1021/jp054732v515Proof of Single-Molecule Sensitivity in Surface Enhanced Raman Scattering (SERS) by Means of a Two-Analyte TechniqueLe Ru, E. C.; Meyer, M.; Etchegoin, P. G.Journal of Physical Chemistry B (2006), 110 (4), 1944-1948CODEN: JPCBFK; ISSN:1520-6106. (American Chemical Society)A method is proposed to pin down unambiguous proof for single-mol. sensitivity in surface enhanced Raman spectroscopy (SERS). The simultaneous use of two analyte mols. enables a clear confirmation of the single (or few)-mol. nature of the signals. This method eliminates most of the uncertainties assocd. with low dye concns. in previous expts. It further shows that single- or few-mol. signals are very common in SERS, both in liqs. and on dry substrates.
- 516Lindquist, N. C.; de Albuquerque, C. D. L.; Sobral-Filho, R. G.; Paci, I.; Brolo, A. G. High-speed imaging of surface-enhanced Raman scattering fluctuations from individual nanoparticles. Nat. Nanotechnol. 2019, 14, 981– 987, DOI: 10.1038/s41565-019-0535-6516High-speed imaging of surface-enhanced Raman scattering fluctuations from individual nanoparticlesLindquist, Nathan C.; de Albuquerque, Carlos Diego L.; Sobral-Filho, Regivaldo G.; Paci, Irina; Brolo, Alexandre G.Nature Nanotechnology (2019), 14 (10), 981-987CODEN: NNAABX; ISSN:1748-3387. (Nature Research)The concept of plasmonic hotspots is central to the interpretation of the surface-enhanced Raman scattering (SERS) effect. Although plasmonic hotspots are generally portrayed as static features, single-mol. SERS (SM-SERS) is marked by characteristic time-dependent fluctuations in signal intensity. The origin of those fluctuations can be assigned to a variety of dynamic and complex processes, including mol. adsorption or desorption, surface diffusion, mol. reorientation and metal surface reconstruction. Since each of these mechanisms simultaneously contributes to a fluctuating SERS signal, probing their relative impact in SM-SERS remains an exptl. challenge. Here, we introduce a super-resoln. imaging technique with an acquisition rate of 800,000 frames per s to probe the spatial and temporal features of the SM-SERS fluctuations from single silver nanoshells. The technique has a spatial resoln. of ∼7 nm. The images reveal short ∼10 μs scattering events localized in various regions on a single nanoparticle. Remarkably, even a fully functionalized nanoparticle was 'dark' more than 98% of the time. The sporadic SERS emission suggests a transient hotspot formation mechanism driven by a random reconstruction of the metallic surface, an effect that dominates over any plasmonic resonance of the particle itself. Our results provide the SERS community with a high-speed exptl. approach to study the fast dynamic properties of SM-SERS hotspots in typical room-temp. exptl. conditions, with possible implications in catalysis and sensing.
- 517de Albuquerque, C. D. L.; Hokanson, K. M.; Thorud, S. R.; Sobral-Filho, R. G.; Lindquist, N. C.; Brolo, A. G. Dynamic Imaging of Multiple SERS Hotspots on Single Nanoparticles. ACS Photonics 2020, 7, 434– 443, DOI: 10.1021/acsphotonics.9b01395517Dynamic Imaging of Multiple SERS Hotspots on Single Nanoparticlesde Albuquerque, Carlos Diego L.; Hokanson, Kallai M.; Thorud, Sarah R.; Sobral-Filho, Regivaldo G.; Lindquist, Nathan C.; Brolo, Alexandre G.ACS Photonics (2020), 7 (2), 434-443CODEN: APCHD5; ISSN:2330-4022. (American Chemical Society)Signal intensity fluctuations are a ubiquitous characteristic of single-mol. surface-enhanced Raman scattering (SERS). In this work, we obsd. SERS intensity fluctuations (SIFs) from single nanoparticles fully coated with an adsorbate layer. Fluctuations from dry, fully coated nanoparticles are assigned to a dynamic mol./metal environment wherein at.-scale reconstructions support SERS. Using super resoln. imaging techniques, we were able to pinpoint the positions of the fluctuations with subparticle precision. We obsd. that the fluctuation events were sepd. spatially, temporally, and were unique to different laser excitation wavelengths and polarizations. Dual-wavelength super-resoln. SERS imaging with green and red lasers reveal various classes of SIFs that occur either simultaneously or nonsimultaneously and from either the same or different location on a single nanoparticle. Similar results were seen when the particle is excited with different polarizations. This suggests that single mol. responses from several different hotspots in the same nanoparticle were readily probed. Furthermore, each nanoparticle contains multiple unique hotspots of different strengths, and resonance conditions, which are accessible by the different illumination conditions. The plasmon resonances localized by the roughness features at the nanoparticle's surface play a significant role in the fluctuation events. Our expts. show that SERS hotspots that support single mols. are not a static feature of the nanoparticle. This information should be useful to guide future single-mol. SERS expts.
- 518Son, J.; Kim, G.-H.; Lee, Y.; Lee, C.; Cha, S.; Nam, J.-M. Toward Quantitative Surface-Enhanced Raman Scattering with Plasmonic Nanoparticles: Multiscale View on Heterogeneities in Particle Morphology, Surface Modification, Interface, and Analytical Protocols. J. Am. Chem. Soc. 2022, 144, 22337– 22351, DOI: 10.1021/jacs.2c05950518Toward Quantitative Surface-Enhanced Raman Scattering with Plasmonic Nanoparticles: Multiscale View on Heterogeneities in Particle Morphology, Surface Modification, Interface, and Analytical ProtocolsSon, Jiwoong; Kim, Gyeong-Hwan; Lee, Yeonhee; Lee, Chungyeon; Cha, Seungsang; Nam, Jwa-MinJournal of the American Chemical Society (2022), 144 (49), 22337-22351CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)A review. Surface-enhanced Raman scattering (SERS) provides significantly enhanced Raman scattering signals from mols. adsorbed on plasmonic nanostructures, as well as the mols.' vibrational fingerprints. Plasmonic nanoparticle systems are particularly powerful for SERS substrates as they provide a wide range of structural features and plasmonic couplings to boost the enhancement, often up to >108-1010. Nevertheless, nanoparticle-based SERS is not widely utilized as a means for reliable quant. measurement of mols. largely due to limited controllability, uniformity, and scalability of plasmonic nanoparticles, poor mol. modification chem., and a lack of widely used anal. protocols for SERS. Furthermore, multiscale issues with plasmonic nanoparticle systems that range from at. and mol. scales to assembled nanostructure scale are difficult to simultaneously control, analyze, and address. In this perspective, we introduce and discuss the design principles and key issues in prepg. SERS nanoparticle substrates and the recent studies on the uniform and controllable synthesis and newly emerging machine learning-based anal. of plasmonic nanoparticle systems for quant. SERS. Specifically, the multiscale point of view with plasmonic nanoparticle systems toward quant. SERS is provided throughout this perspective. Furthermore, issues with correctly estg. and comparing SERS enhancement factors are discussed, and newly emerging statistical and artificial intelligence approaches for analyzing complex SERS systems are introduced and scrutinized to address challenges that cannot be fully resolved through synthetic improvements.
- 519Porter, M. D.; Granger, J. H. Surface-enhanced Raman scattering II: concluding remarks. Faraday Discuss. 2017, 205, 601– 613, DOI: 10.1039/C7FD00206H519Surface-enhanced Raman scattering II: concluding remarksPorter, Marc D.; Granger, Jennifer H.Faraday Discussions (2017), 205 (Surface Enhanced Raman Scattering--SERS), 601-613CODEN: FDISE6; ISSN:1359-6640. (Royal Society of Chemistry)Surface-enhanced Raman scattering (SERS) enables the detection of a large no. of different adsorbates at extraordinarily low levels. This plasmonics-based technol. has undergone a no. of remarkable advances since its discovery over 40 years ago, and has emerged from being an investigative tool confined largely to the research lab. into a much more usable tool across a broad range of investigative studies, both within the lab. and beyond. The purpose of this Concluding remarks manuscript is to capture, at least in part, the developments in this area since the first Faraday discussion of SERS over a decade ago. It begins with a brief contextual overview and then moves into describing a few of the many highlights from the meeting. Along the way, we have added a few comments and perspectives as a means to more fully stage where the different areas of research with SERS stand today. An addendum is included that collects a few of the recent perspectives on the original work and activities in this area.
- 520De Silva Indrasekara, A. S.; Johnson, S. F.; Odion, R. A.; Vo-Dinh, T. Manipulation of the Geometry and Modulation of the Optical Response of Surfactant-Free Gold Nanostars: A Systematic Bottom-Up Synthesis. ACS Omega 2018, 3, 2202– 2210, DOI: 10.1021/acsomega.7b01700520Manipulation of the Geometry and Modulation of the Optical Response of Surfactant-Free Gold Nanostars: A Systematic Bottom-Up SynthesisDe Silva Indrasekara, Agampodi S.; Johnson, Sean F.; Odion, Ren A.; Vo-Dinh, TuanACS Omega (2018), 3 (2), 2202-2210CODEN: ACSODF; ISSN:2470-1343. (American Chemical Society)The optimization of the bottom-up synthesis that improves the reproducibility and homogeneity of Au-branched nanoparticles and the modulation of their morphol., particularly the branch d., geometrical features of the branches to obtain the desired optical properties. is presented. The order of reagent addn. is crucial for improved homogeneity of the branched nature of nanoparticles that enable a high batch-batch reproducibility and reliability. A different combination of the synthesis parameters, in particular, additive halides and concn. ratios of reactive Au to Ag and Au to Au seeds, which yield branched nanoparticle of similar localized surface plasmon resonances but with distinguishable changes in the dimensions of the branches, was realized. The study introduces the design parameters for the purpose-tailored manufg. of surfactant-free Au nanostars in a reliable manner.
- 521Song, T.; Gao, F.; Guo, S.; Zhang, Y.; Li, S.; You, H.; Du, Y. A review of the role and mechanism of surfactants in the morphology control of metal nanoparticles. Nanoscale 2021, 13, 3895– 3910, DOI: 10.1039/D0NR07339C521A review of the role and mechanism of surfactants in the morphology control of metal nanoparticlesSong, Tongxin; Gao, Fei; Guo, Siyu; Zhang, Yangping; Li, Shujin; You, Huaming; Du, YukouNanoscale (2021), 13 (7), 3895-3910CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)A review. Although great progress has been made in the synthesis of metal nanoparticles, good repeatability and accurate predictability are still difficult to achieve. This difficulty can be attributed to the synthetic method based primarily on observation and subjective experience, and the role of many surfactants remains unclear. It should be noted that surfactants play an important role in the synthetic process. Understanding their function and mechanism in the synthetic process is a prerequisite for the rational design of nanocatalysts with ideal morphol. and performance. In this review article, the function of surfactants is introduced first, and then the mechanism of action of surfactants in controlling the morphol. of nanoparticles is discussed according to the types of surfactants, and the promoting and sealing effects of surfactants on the crystal surface is revealed. The relationship between surfactants and the morphol. structure of nanoparticles is studied. The removal methods of surfactants are discussed, and the existing problems in the current development strategy are summarized. Finally, the application of surfactants in controlling the morphol. of metal nanocrystals is prospected. It is hoped that the review can open up new avenues for the synthesis of nanocrystals.
- 522Hossain, M. K. Nanoassembly of gold nanoparticles: An active substrate for size-dependent surface-enhanced Raman scattering. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 2020, 242, 118759, DOI: 10.1016/j.saa.2020.118759There is no corresponding record for this reference.
- 523Zhou, H.; Zhang, J.; Li, B.; Liu, J.; Xu, J.-J.; Chen, H.-Y. Dual-Mode SERS and Electrochemical Detection of miRNA Based on Popcorn-like Gold Nanofilms and Toehold-Mediated Strand Displacement Amplification Reaction. Anal. Chem. 2021, 93, 6120– 6127, DOI: 10.1021/acs.analchem.0c05221523Dual-Mode SERS and Electrochemical Detection of miRNA Based on Popcorn-like Gold Nanofilms and Toehold-Mediated Strand Displacement Amplification ReactionZhou, Hong; Zhang, Jishou; Li, Binxiao; Liu, Jing; Xu, Jing-Juan; Chen, Hong-YuanAnalytical Chemistry (Washington, DC, United States) (2021), 93 (15), 6120-6127CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)MicroRNA (miRNA) has emerged as one of the ideal target biomarker analytes for cancer detection because its abnormal expression is closely related to the occurrence of many cancers. In this work, we combined three-dimensional (3D) popcorn-like gold nanofilms as novel surface-enhanced Raman scattering (SERS)-electrochem. active substrates with toehold-mediated strand displacement reactions (TSDRs) to construct a DNA mol. machine for SERS-electrochem. dual-mode detection of miRNA. 3D popcorn-like spatial structures generated more active "hot spots" and thus enhanced the sensitivity of SERS and electrochem. signals. Besides, the TSDRs showed high sequence-dependence and high specificity. The addn. of target miRNA will trigger the mol. machine to perform two TSDRs in the presence of signal DNA strands modified by R6G (R6G-DNA), thus achieving an enzyme-free amplification detection of miRNA with a low limit of detection of 0.12 fM (for the SERS method) and 2.2 fM (for the electrochem. method). This biosensor can also serve as a universally amplified and sensitive detection platform for monitoring different biomarkers, such as cancer-related DNA, mRNA, or miRNA mols., with high selectivity by changing the corresponding probe sequence.
- 524Cortese, M.; Gigliobianco, M. R.; Magnoni, F.; Censi, R.; Di Martino, P. Compensate for or Minimize Matrix Effects? Strategies for Overcoming Matrix Effects in Liquid Chromatography-Mass Spectrometry Technique: A Tutorial Review. Molecules 2020, 25, 3047, DOI: 10.3390/molecules25133047524Compensate for or minimize matrix effects? Strategies for overcoming matrix effects in liquid chromatography-mass spectrometry technique: a tutorial reviewCortese, Manuela; Gigliobianco, Maria Rosa; Magnoni, Federico; Censi, Roberta; Di Martino, PieraMolecules (2020), 25 (13), 3047CODEN: MOLEFW; ISSN:1420-3049. (MDPI AG)A review. In recent decades, mass spectrometry techniques, particularly when combined with sepn. methods such as high-performance liq. chromatog., have become increasingly important in pharmaceutical, bio-anal., environmental, and food science applications because they afford high selectivity and sensitivity. However, mass spectrometry has limitations due to the matrix effects (ME), which can be particularly marked in complex mixes, when the analyte co-elutes together with other mols., altering anal. results quant. This may be detrimental during method validation, neg. affecting reproducibility, linearity, selectivity, accuracy, and sensitivity. Starting from literature and own experience, this review intends to provide a simple guideline for selecting the best operative conditions to overcome matrix effects in LC-MS techniques, to obtain the best result in the shortest time. The proposed methodol. can be of benefit in different sectors, such as pharmaceutical, bio-anal., environmental, and food sciences. Depending on the required sensitivity, analysts may minimize or compensate for ME. When sensitivity is crucial, anal. must try to minimize ME by adjusting MS parameters, chromatog. conditions, or optimizing clean-up. On the contrary, to compensate for ME analysts should have recourse to calibration approaches depending on the availability of blank matrix. When blank matrixes are available, calibration can occur through isotope labeled internal stds. and matrix matched calibration stds. conversely, when blank matrixes are not available, calibration can be performed through isotope labeled internal stds., background subtraction, or surrogate matrixes. In any case, an adjusting of MS parameters, chromatog. conditions, or a clean-up are necessary.
- 525Zhang, D.; Xie, Y.; Deb, S. K.; Davison, V. J.; Ben-Amotz, D. Isotope Edited Internal Standard Method for Quantitative Surface-Enhanced Raman Spectroscopy. Anal. Chem. 2005, 77, 3563– 3569, DOI: 10.1021/ac050338h525Isotope Edited Internal Standard Method for Quantitative Surface-Enhanced Raman SpectroscopyZhang, Dongmao; Xie, Yong; Deb, Shirshendu K.; Davison, V. Jo; Ben-Amotz, DorAnalytical Chemistry (2005), 77 (11), 3563-3569CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)A new isotope edited internal std. (IEIS) method for quant. surface-enhanced Raman spectroscopy (SERS) is demonstrated using rhodamine 6G (R6G-d0) and rhodamine 6G (R6G-d4) edited with deuterium. The reproducibility and accuracy of the IEIS method is investigated both under optical resonance (SERRS) and nonresonance (SERS) conditions. A batch-to-batch concn. measurement reproducibility of better than 3% is demonstrated over a concn. range of 200 pM-2 μM with up to a factor of 3 difference between the concn. of the analyte and its IEIS. The superior performance of the IEIS method is further illustrated by comparing results obtained using abs. SERS/SERRS intensity calibration (with no internal std.) or using adenine (rather than R6G-d4) as an internal std. for R6G concn. quantization. Potential biomedical gene expression and comparative proteomic applications of the IEIS method are discussed.
- 526Zong, C.; Xu, M.; Xu, L.-J.; Wei, T.; Ma, X.; Zheng, X.-S.; Hu, R.; Ren, B. Surface-Enhanced Raman Spectroscopy for Bioanalysis: Reliability and Challenges. Chem. Rev. 2018, 118, 4946– 4980, DOI: 10.1021/acs.chemrev.7b00668526Surface-Enhanced Raman Spectroscopy for Bioanalysis: Reliability and ChallengesZong, Cheng; Xu, Mengxi; Xu, Li-Jia; Wei, Ting; Ma, Xin; Zheng, Xiao-Shan; Hu, Ren; Ren, BinChemical Reviews (Washington, DC, United States) (2018), 118 (10), 4946-4980CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review. Surface-enhanced Raman spectroscopy (SERS) inherits the rich chem. fingerprint information on Raman spectroscopy and gains sensitivity by plasmon-enhanced excitation and scattering. In particular, most Raman peaks have a narrow width suitable for multiplex anal., and the measurements can be conveniently made under ambient and aq. conditions. These merits make SERS a very promising technique for studying complex biol. systems, and SERS has attracted increasing interest in biorelated anal. However, there are still great challenges that need to be addressed until it can be widely accepted by the biorelated communities, answer interesting biol. questions, and solve fatal clin. problems. SERS applications in bioanal. involve the complex interactions of plasmonic nanomaterials with biol. systems and their environments. The reliability becomes the key issue of bioanal. SERS to ext. meaningful information from SERS data. This review provides a comprehensive overview of bioanal. SERS with the main focus on the reliability issue. The authors first introduce the mechanism of SERS to guide the design of reliable SERS expts. with high detection sensitivity. The authors then introduce the current understanding of the interaction of nanomaterials with biol. systems, mainly living cells, to guide the design of functionalized SERS nanoparticles for target detection. The authors further introduce the current status of label-free (direct) and labeled (indirect) SERS detections, for systems from biomols., to pathogens, to living cells, and the potential interferences from exptl. design, measurement conditions, and data anal are discussed. In the end, the authors give an outlook of the key challenges in bioanal. SERS, including reproducibility, sensitivity, and spatial and time resoln.
- 527Deb, S. K.; Davis, B.; Ben-Amotz, D.; Davisson, V. J. Accurate Concentration Measurements Using Surface-Enhanced Raman and Deuterium Exchanged Dye Pairs. Appl. Spectrosc. 2008, 62, 1001– 1007, DOI: 10.1366/000370208785793290527Accurate concentration measurements using surface-enhanced Raman and deuterium exchanged dye pairsDeb, Shirshendu K.; Davis, Brandon; Ben-Amotz, Dor; Davisson, V. JoApplied Spectroscopy (2008), 62 (9), 1001-1007CODEN: APSPA4; ISSN:0003-7028. (Society for Applied Spectroscopy)Quant. applications of surface-enhanced resonance Raman scattering (SERRS) are often limited by the reproducibility of SERRS intensities, given the difficulty of controlling analyte-substrate interactions and the assocd. local field enhancement. As demonstrated here, SERRS from dye mols. even within the same structural class that compete with similar substrates display distinct spectral intensities that are not proportional to analyte concns., which limits their use as internal standardization probes and/or for multiplex anal. Recently, we demonstrated that isotopic variants of rhodamine 6G (R6G), namely R6G-d0 and R6G-d4, can be used for internal stds. in SERRS expts. with a linear optical response from picomolar to micromolar concns. (of total analytes). Here we extend these results by describing a straightforward method for obtaining isotopomeric pairs of other Raman active dyes by hydrogen-deuterium exchange conditions for substitution at electron-rich arom. heterocycles. Most of the known SERRS active probes can be converted into the corresponding isotopomeric mol. by this exchange method, which significantly expands the scope of the isotopic edited internal std. (IEIS) approach. The relative quantification using IEIS enables accurate, reproducible (residual std. deviation ±2.2%) concn. measurements over a range of 200 pM to 2 μM. These studies enable easy access to a variety of isotopically substituted Raman active dyes and establish the generality of the methodol. for quant. SERRS measurements. For the first time, three rhodamine 6G isotopomers have been created and show distinct Raman spectra, demonstrating the principle of the approach for application as a multiplex technique in biomol. detection/quantification.
- 528Yin, P.-G.; Jiang, L.; Lang, X.-F.; Guo, L.; Yang, S. Quantitative analysis of mononucleotides by isotopic labeling surface-enhanced Raman scattering spectroscopy. Biosens. Bioelectron. 2011, 26, 4828– 4831, DOI: 10.1016/j.bios.2011.05.042There is no corresponding record for this reference.
- 529Subaihi, A.; Xu, Y.; Muhamadali, H.; Mutter, S. T.; Blanch, E. W.; Ellis, D. I.; Goodacre, R. Towards improved quantitative analysis using surface-enhanced Raman scattering incorporating internal isotope labelling. Analytical Methods 2017, 9, 6636– 6644, DOI: 10.1039/C7AY02527KThere is no corresponding record for this reference.
- 530Qin, L.; Zhang, X.; Wu, J.; Zhang, W.; Lu, X.; Sun, H.; Zhang, J.; Guo, L.; Xie, J. Quantification and toxicokinetics of paraquat in mouse plasma and lung tissues by internal standard surface-enhanced Raman spectroscopy. Anal. Bioanal. Chem. 2022, 414, 2371– 2383, DOI: 10.1007/s00216-022-03875-1There is no corresponding record for this reference.
- 531Guo, P.; Zeng, W.; Tian, S.; Chen, H.; Liu, W.; Chen, C. Quantitative detection of nanomolar drug using surface-enhanced Raman scattering combined with internal standard method and two-step centrifugation method. Microchemical Journal 2020, 158, 105202, DOI: 10.1016/j.microc.2020.105202There is no corresponding record for this reference.
- 532Wu, Y.; Liu, J.; Xu, R.; Li, J.; Fu, C.; Shi, W.; Chen, J. Recent advances in ratiometric surface-enhanced Raman spectroscopy sensing strategies. Microchemical Journal 2024, 199, 110127, DOI: 10.1016/j.microc.2024.110127There is no corresponding record for this reference.
- 533Wei, W.; Hassan, M. M.; Wu, J.; Mu, X.; Li, H.; Chen, Q. Competitive Ratiometric Aptasensing with Core-Internal Standard-Shell Structure Based on Surface-Enhanced Raman Scattering. J. Agric. Food Chem. 2023, 71, 857– 866, DOI: 10.1021/acs.jafc.2c06850There is no corresponding record for this reference.
- 534Jiang, X.; Tan, Z.; Lin, L.; He, J.; He, C.; Thackray, B. D.; Zhang, Y.; Ye, J. Surface-Enhanced Raman Nanoprobes with Embedded Standards for Quantitative Cholesterol Detection. Small Methods 2018, 2, 1800182, DOI: 10.1002/smtd.201800182There is no corresponding record for this reference.
- 535Li, M.; Wang, J.-Y.; Chen, Q.-Q.; Lin, L.-H.; Radjenovic, P.; Zhang, H.; Luo, S.-Y.; Tian, Z.-Q.; Li, J.-F. Background-Free Quantitative Surface Enhanced Raman Spectroscopy Analysis Using Core–Shell Nanoparticles with an Inherent Internal Standard. Anal. Chem. 2019, 91, 15025– 15031, DOI: 10.1021/acs.analchem.9b03703535Background-Free Quantitative Surface Enhanced Raman Spectroscopy Analysis Using Core-Shell Nanoparticles with an Inherent Internal StandardLi, Mei; Wang, Jing-Yu; Chen, Qing-Qi; Lin, Long-Hui; Radjenovic, Petar; Zhang, Hua; Luo, Shi-Yi; Tian, Zhong-Qun; Li, Jian-FengAnalytical Chemistry (Washington, DC, United States) (2019), 91 (23), 15025-15031CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Surface enhanced Raman spectroscopy (SERS) is an ultrasensitive label-free anal. technique that can provide unique chem. and structural fingerprint information. However, gaining reliable quant. anal. with SERS remains a huge challenge because of poor reproducibility and the instability of nanostructured SERS active surfaces. Herein, an effective strategy of coating Au nanoparticles (NPs) with ultra-thin and uniform Prussian blue (PB) shell (Au@PB NPs) was developed for quant. detection of dopamine (DA) concns. in blood serum and crystal violet (CV) contaminants in lake water. The only intense PB Raman signal at 2155 cm-1 served as an ideal and interference-free internal std. (IS) for correcting fluctuations in the Raman intensities of analytes. Also, the stability of Au@PB NPs was investigated, exhibiting good functionality in strong acid solns. and thermal stability at 100°. This work demonstrates a convenient and fast quant. SERS technique for detecting analyte concns. in complex systems and has a great no. of potential applications for use in anal. chem.
- 536Mei, R.; Wang, Y.; Shi, S.; Zhao, X.; Zhang, Z.; Wang, X.; Shen, D.; Kang, Q.; Chen, L. Highly Sensitive and Reliable Internal-Standard Surface-Enhanced Raman Scattering Microneedles for Determination of Bacterial Metabolites as Infection Biomarkers in Skin Interstitial Fluid. Anal. Chem. 2022, 94, 16069– 16078, DOI: 10.1021/acs.analchem.2c03208536Highly Sensitive and Reliable Internal-Standard Surface-Enhanced Raman Scattering Microneedles for Determination of Bacterial Metabolites as Infection Biomarkers in Skin Interstitial FluidMei, Rongchao; Wang, Yunqing; Shi, Shang; Zhao, Xizhen; Zhang, Zhiyang; Wang, Xiaoyan; Shen, Dazhong; Kang, Qi; Chen, LingxinAnalytical Chemistry (Washington, DC, United States) (2022), 94 (46), 16069-16078CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Microneedles (MNs) are currently one of the most promising tools for skin interstitial fluid (ISF)-based biosensing, while it is still a challenge to expand the detectable biomarkers in ISF due to limited MNs types and detection techniques. Herein, highly sensitive internal-std. surface-enhanced Raman scattering microneedles (IS-SERS-MNs) were developed, which enabled the reliable detection of bacterial metabolites in ISF as new detectable biomarkers for infection diagnosis. The developed IS-SERS-MNs can not only directly detect pyocyanin (a representative bacterial metabolite) present in mouse dermal ISF but also indirectly detect pyocyanin in the hypodermis via its diffusion into the dermis, revealing a new possible pathway for the source of biomarkers in dermal ISF. Moreover, the SERS signal of pyocyanin was also clearly detected at real mouse wounds, indicating that the developed IS-SERS-MNs have great potential in minimally invasive and painless diagnosis of bacterial infection via a new ISF route. This work not only develops IS-SERS-MNs as a powerful tool for expanding the application of SERS-based MNs but also provides a new chance for ISF-related infection diagnosis.
- 537Zou, Y.; Chen, L.; Song, Z.; Ding, D.; Chen, Y.; Xu, Y.; Wang, S.; Lai, X.; Zhang, Y.; Sun, Y.; Chen, Z.; Tan, W. Stable and unique graphitic Raman internal standard nanocapsules for surface-enhanced Raman spectroscopy quantitative analysis. Nano Research 2016, 9, 1418– 1425, DOI: 10.1007/s12274-016-1037-6There is no corresponding record for this reference.
- 538Tian, H.; Zhang, N.; Tong, L.; Zhang, J. In Situ Quantitative Graphene-Based Surface-Enhanced Raman Spectroscopy. Small Methods 2017, 1, 1700126, DOI: 10.1002/smtd.201700126There is no corresponding record for this reference.
- 539Gao, J.; Zhao, C.; Zhang, Z.; Li, G. An intrinsic internal standard substrate of Au@PS-b-P4VP for rapid quantification by surface enhanced Raman scattering. Analyst 2017, 142, 2936– 2944, DOI: 10.1039/C7AN01061C539An intrinsic internal standard substrate of Au@PS-b-P4VP for rapid quantification by surface enhanced Raman scatteringGao, Jiamin; Zhao, Cheng; Zhang, Zhuomin; Li, GongkeAnalyst (Cambridge, United Kingdom) (2017), 142 (16), 2936-2944CODEN: ANALAO; ISSN:0003-2654. (Royal Society of Chemistry)Reliable quantification by surface enhanced Raman scattering (SERS) highly depends on the development of a reproducible substrate with excellent anti-interference capability. In this work, an intrinsic internal std. (IS) SERS substrate based on a diblock copolymer, polystyrene-block-poly-4-vinylpyridine (PS-b-P4VP), as a template was developed by a modified block copolymer lithog. (BCL) technique of reserving the diblock copolymer template. This substrate generated a stable vibration peak at 1066 cm-1 attributed to poly(4-vinylpyridine) (P4VP) which could be used as an intrinsic IS for precise SERS quantification. A series of characterization results showed that the diblock copolymer template endowed this substrate with homogeneous distribution of Au nanoparticles, excellent stability and reproducibility. A minor relative std. deviation (RSDs) of SERS responses at 1066 cm-1 was measured and calcd. to be 4.3% from ten different substrates in the same batch, which suggested good substrate-to-substrate reproducibility of this substrate. Finally, this intrinsic IS substrate was successfully applied for the rapid quantification of a trace banned dye, chrysoidine, in food samples with complicated matrixes by SERS. It was proved that chrysoidine could be found and quantified to be 0.50 and 0.41 mg L-1 in a pos. dried bean curd stick and chilli powder sample resp. with good recoveries by this substrate coupled with SERS. The development of intrinsic IS substrates would benefit rapid and accurate quantification of trace targets in complex samples coupled with SERS anal.
- 540Ameer, F. S.; Hu, W.; Ansar, S. M.; Siriwardana, K.; Collier, W. E.; Zou, S.; Zhang, D. Robust and Reproducible Quantification of SERS Enhancement Factors Using a Combination of Time-Resolved Raman Spectroscopy and Solvent Internal Reference Method. J. Phys. Chem. C 2013, 117, 3483– 3488, DOI: 10.1021/jp311752m540Robust and Reproducible Quantification of SERS Enhancement Factors Using a Combination of Time-Resolved Raman Spectroscopy and Solvent Internal Reference MethodAmeer, Fathima S.; Hu, Wenfang; Ansar, Siyam M.; Siriwardana, Kumudu; Collier, Willard E.; Zou, Shengli; Zhang, DongmaoJournal of Physical Chemistry C (2013), 117 (7), 3483-3488CODEN: JPCCCK; ISSN:1932-7447. (American Chemical Society)Recent research has demonstrated that the nanoparticle (NP) surface enhanced Raman spectroscopy (SERS) substrate modifies an analyte's Raman signal through two competitive mechanisms, SERS enhancement and NP inner filter effect, instead of SERS enhancement alone as commonly believed. Using a combination of time-resolved Raman spectroscopy and a solvent internal ref. method, reported herein is a quant. detn. of the SERS enhancement factors (EFs) of mercaptobenzimidazole (MBI), a model organothiol, adsorbed onto gold and silver nanoparticles (AuNPs and AgNPs). The peak MBI SERS EF depends only on the type and size of NPs, but not analyte and NP concns., or the type (KF, KCl, KBr, and K2SO4) and concns. of the electrolytic aggregation agents. The exptl. SERS EFs of MBI on both AuNPs and AgNPs can be fully explained by the electromagnetic mechanism alone. This result, combined with our recent findings that a series of structurally diverse organothiols have similar SERS EFs, argues quite strongly against the possibility of large chem. enhancement (e.g., >10 times) for organothiols adsorbed onto colloidal AuNPs and AgNPs.
- 541Yu, F.; Su, M.; Tian, L.; Wang, H.; Liu, H. Organic Solvent as Internal Standards for Quantitative and High-Throughput Liquid Interfacial SERS Analysis in Complex Media. Anal. Chem. 2018, 90, 5232– 5238, DOI: 10.1021/acs.analchem.8b00008541Organic Solvent as Internal Standards for Quantitative and High-Throughput Liquid Interfacial SERS Analysis in Complex MediaYu, Fanfan; Su, Mengke; Tian, Li; Wang, Hongyan; Liu, HonglinAnalytical Chemistry (Washington, DC, United States) (2018), 90 (8), 5232-5238CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Liq.-state interfacial nanoparticle arrays for surface-enhanced Raman scattering (SERS) promises a practical, substrate-free, and rapid anal. but faces a great challenge to develop a batch and uniform fabrication strategy with stable internal stds. (IS) because of the difficulties in precisely locating both the IS tags and analytes in the same local structure under the harsh conditions of biphasic liq. interface. Here, the authors develop a fast batch prepn. of self-ordered dense Au nanoparticle (GNP) arrays on cyclohexane/water biphasic interface in 96-well plates with the assist of acetone as the phase-crossing inducer. The acetone can ext. the pesticide mols. via a simple dipping sample peels and can rapidly capture and locate the pesticide mol. into the plasmonic hotspots. Meanwhile, this phase-crossing solvent, acetone itself, generates stable SERS signal and was used as the IS tags to calibrate the signal fluctuation. This platform presents an excellent uniformity with a relative std. deviation of 5.9% compared to the relative std. deviation of 14.5% without the IS's correction and a good sensitivity with a limit of detection (LOD) of 1 nM thiram. This high-throughput strategy for analyzing pesticide residues at fruit peels reached detection levels of nanograms per square centimeter (ng/cm2). Combined with the 96-well plates, this platform greatly facilitates the self-assembly and multiplex sampling. The self-ordered arrays at two immiscible phases interface evidenced the detection of both the oil-sol. thiabendazole and the water-sol. thiram mols. and also realized the multiplex and two-phase detection of these two pesticides. This platform offers vast possibilities for on-site sensing of various analytes and paves a new way for the quant. and high-throughput SERS analyzer just as convenient as the microplate reader.
- 542Li, D.; Zhang, Z.; Wang, X.; Wang, Y.; Gao, X.; Li, Y. A direct method for detecting proteins in body fluids by Surface-Enhanced Raman Spectroscopy under native conditions. Biosens. Bioelectron. 2022, 200, 113907, DOI: 10.1016/j.bios.2021.113907542A direct method for detecting proteins in body fluids by Surface-Enhanced Raman Spectroscopy under native conditionsLi, Dan; Zhang, Zhe; Wang, Xiaotong; Wang, Yunpeng; Gao, Xin; Li, YangBiosensors & Bioelectronics (2022), 200 (), 113907CODEN: BBIOE4; ISSN:0956-5663. (Elsevier B.V.)Surface enhanced Raman spectroscopy (SERS) is widely used in biomol. detection. However, maintaining the native structure of proteins while obtaining sensitive and reproducible SERS signals of unlabeled proteins remains a challenge. In this study, dichloromethane (DCM) and CaCl2 were used to optimize the aggregation of Ag nanoparticles (AgNPs), and several proteins were analyzed comprehensively. Calcium ions removed citrate ions outside AgNPs, inducing hot spots and achieving high-sensitivity SERS signals of proteins. Furthermore, 20 random samples of 0.5μg/mL Hb were analyzed by this method. The obtained spectra showed good repeatability and a high quality. Using the peak intensity of DCM as internal parameter, the differences in peak intensities at the same position were analyzed to distinguish different proteins and evaluate changes in protein structure. Subsequently, the protein content in protein mixts. and serum was quantified and a good linear relationship between peak intensity and protein concn. was obtained. This method shows great promise in the fields of food testing and clin. diagnosis.
- 543Nam, W.; Zhao, Y.; Song, J.; Ali Safiabadi Tali, S.; Kang, S.; Zhu, W.; Lezec, H. J.; Agrawal, A.; Vikesland, P. J.; Zhou, W. Plasmonic Electronic Raman Scattering as Internal Standard for Spatial and Temporal Calibration in Quantitative Surface-Enhanced Raman Spectroscopy. J. Phys. Chem. Lett. 2020, 11, 9543– 9551, DOI: 10.1021/acs.jpclett.0c03056543Plasmonic Electronic Raman Scattering as Internal Standard for Spatial and Temporal Calibration in Quantitative Surface-Enhanced Raman SpectroscopyNam, Wonil; Zhao, Yuming; Song, Junyeob; Ali Safiabadi Tali, Seied; Kang, Seju; Zhu, Wenqi; Lezec, Henri J.; Agrawal, Amit; Vikesland, Peter J.; Zhou, WeiJournal of Physical Chemistry Letters (2020), 11 (22), 9543-9551CODEN: JPCLCD; ISSN:1948-7185. (American Chemical Society)Ultrasensitive surface-enhanced Raman spectroscopy (SERS) still faces difficulties in quant. anal. because of its susceptibility to local optical field variations at plasmonic hotspots in metallo-dielec. nanostructures. Current SERS calibration approaches using Raman tags have inherent limitations due to spatial occupation competition with analyte mols., spectral interference with analyte Raman peaks, and photodegrdn. Herein, we report that plasmon-enhanced electronic Raman scattering (ERS) signals from metal can serve as an internal std. for spatial and temporal calibration of mol. Raman scattering (MRS) signals from analyte mols. at the same hotspots, enabling rigorous quant. SERS anal. We observe a linear dependence between ERS and MRS signal intensities upon spatial and temporal variations of excitation optical fields, manifesting the |E|4 enhancements for both ERS and MRS processes at the same hotspots in agreement with our theor. prediction. Furthermore, we find that the ERS calibration's performance limit can result from orientation variations of analyte mols. at hotspots.
- 544Kiefl, E. J.; Kiefl, R. F.; dos Santos, D. P.; Brolo, A. G. Evaluation of Surface-Enhanced Raman Spectroscopy Substrates from Single-Molecule Statistics. J. Phys. Chem. C 2017, 121, 25487– 25493, DOI: 10.1021/acs.jpcc.7b08691544Evaluation of Surface-Enhanced Raman Spectroscopy Substrates from Single-Molecule StatisticsKiefl, Evan J.; Kiefl, Robert F.; dos Santos, Diego P.; Brolo, Alexandre G.Journal of Physical Chemistry C (2017), 121 (45), 25487-25493CODEN: JPCCCK; ISSN:1932-7447. (American Chemical Society)Accurate quantification of substrate characteristics is a central pursuit within the field of surface-enhanced Raman spectroscopy (SERS). A theory based on single-mol. SERS (SM-SERS) statistics was developed for comprehensive substrate evaluation. This approach is applicable to general substrates possessing many hotspots and is capable of quantifying hotspot strength variation using a min. set of fitting parameters. The model was validated for simulated substrates and then applied to the SM-SERS statistics of a roughened Ag electrode, for which the degree of hotspot uniformity was quantified. The fitted model parameters provide important information concerning the structure-activity relation of hotspots and can be used to directly compare SERS substrates. Overall, the results present an exptl. determinable parameter set that potentially improves upon the widely used av. enhancement factor metric currently used for SERS substrate evaluation.
- 545Fukunaga, Y.; Okada, T. Quantification using statistical parameters derived from signal intensity distributions in surface enhanced Raman scattering (SERS). Anal. Chim. Acta 2021, 1181, 338931, DOI: 10.1016/j.aca.2021.338931545Quantification using statistical parameters derived from signal intensity distributions in surface enhanced Raman scattering (SERS)Fukunaga, Yu; Okada, TetsuoAnalytica Chimica Acta (2021), 1181 (), 338931CODEN: ACACAM; ISSN:0003-2670. (Elsevier B.V.)Raman spectroscopy is a powerful method, which provides information on mol. structures, conformations, interactions etc. However, its applications are severely restricted because of low sensitivity. Although surface enhanced Raman scattering (SERS) significantly enhances sensitivity and enables single-mol. detection, quantification by this method is still challenging because of large signal fluctuations. In the present study, the signal intensity distributions (SIDs) in SERS of adenine and thymine on the silver nanoparticle (AgNP) platform are analyzed based on more than 10000 spectra to pursue the possibility of SERS quantification. The signals always involve large fluctuations but show statistically relevant patterns. SIDs are well represented by the exponentially modified Gaussian function, which is characterized by reproducible parameters. Thus, robust quantification is feasible using the parameters derived from the SIDs. At least 200 spectra for a given concn. are necessary to derive reproducible parameter values from the SID. The mean signal intensity detd. from the SIDs is proportional to the adenine concn. in the range of 10-75 μM. However, this parameter becomes independent of the adenine concn. in the lower concn. range. In such concns., minor events, which give distinct SERS spectra, occasionally occur but have only marginal impacts on the mean signal intensity. The cor. std. deviation of the SID, which is estd. from the complementary error function, well represents the minor events and provides a clear correlation with the concn. in the range of 0.5-7.5 μM. Furthermore, the quantification in the nanomolar range is made possible by the incorporation of sample freezing, which enables to enrich target analytes and AgNPs in a liq. phase confined by ice.
- 546Brulé, T.; Bouhelier, A.; Yockell-Lelièvre, H.; Clément, J.-E.; Leray, A.; Dereux, A.; Finot, E. Statistical and Fourier Analysis for In-line Concentration Sensitivity in Single Molecule Dynamic-SERS. ACS Photonics 2015, 2, 1266– 1271, DOI: 10.1021/acsphotonics.5b00134There is no corresponding record for this reference.
- 547Fornasaro, S.; Alsamad, F.; Baia, M.; Batista de Carvalho, L. A. E.; Beleites, C.; Byrne, H. J.; Chiadò, A.; Chis, M.; Chisanga, M.; Daniel, A.; Dybas, J.; Eppe, G.; Falgayrac, G.; Faulds, K.; Gebavi, H.; Giorgis, F.; Goodacre, R.; Graham, D.; La Manna, P.; Laing, S.; Litti, L.; Lyng, F. M.; Malek, K.; Malherbe, C.; Marques, M. P. M.; Meneghetti, M.; Mitri, E.; Mohaček-Grošev, V.; Morasso, C.; Muhamadali, H.; Musto, P.; Novara, C.; Pannico, M.; Penel, G.; Piot, O.; Rindzevicius, T.; Rusu, E. A.; Schmidt, M. S.; Sergo, V.; Sockalingum, G. D.; Untereiner, V.; Vanna, R.; Wiercigroch, E.; Bonifacio, A. Surface Enhanced Raman Spectroscopy for Quantitative Analysis: Results of a Large-Scale European Multi-Instrument Interlaboratory Study. Anal. Chem. 2020, 92, 4053– 4064, DOI: 10.1021/acs.analchem.9b05658547Surface Enhanced Raman Spectroscopy for Quantitative Analysis: Results of a Large-Scale European Multi-Instrument Interlaboratory StudyFornasaro, Stefano; Alsamad, Fatima; Baia, Monica; Batista de Carvalho, Luis A. E.; Beleites, Claudia; Byrne, Hugh J.; Chiado, Alessandro; Chis, Mihaela; Chisanga, Malama; Daniel, Amuthachelvi; Dybas, Jakub; Eppe, Gauthier; Falgayrac, Guillaume; Faulds, Karen; Gebavi, Hrvoje; Giorgis, Fabrizio; Goodacre, Royston; Graham, Duncan; La Manna, Pietro; Laing, Stacey; Litti, Lucio; Lyng, Fiona M.; Malek, Kamilla; Malherbe, Cedric; Marques, Maria P. M.; Meneghetti, Moreno; Mitri, Elisa; Mohacek-Grosev, Vlasta; Morasso, Carlo; Muhamadali, Howbeer; Musto, Pellegrino; Novara, Chiara; Pannico, Marianna; Penel, Guillaume; Piot, Olivier; Rindzevicius, Tomas; Rusu, Elena A.; Schmidt, Michael S.; Sergo, Valter; Sockalingum, Ganesh D.; Untereiner, Valerie; Vanna, Renzo; Wiercigroch, Ewelina; Bonifacio, AloisAnalytical Chemistry (Washington, DC, United States) (2020), 92 (5), 4053-4064CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Surface-enhanced Raman scattering (SERS) is a powerful and sensitive technique for the detection of fingerprint signals of mols. and for the investigation of a series of surface chem. reactions. Many studies introduced quant. applications of SERS in various fields, and several SERS methods have been implemented for each specific application, ranging in performance characteristics, analytes used, instruments, and anal. matrixes. In general, very few methods have been validated according to international guidelines. As a consequence, the application of SERS in highly regulated environments is still considered risky, and the perception of a poorly reproducible and insufficiently robust anal. technique has persistently retarded its routine implementation. Collaborative trials are a type of interlab. study (ILS) frequently performed to ascertain the quality of a single anal. method. The idea of an ILS of quantification with SERS arose within the framework of Working Group 1 (WG1) of the EU COST Action BM1401 Raman4Clinics in an effort to overcome the problematic perception of quant. SERS methods. Here, we report the first interlab. SERS study ever conducted, involving 15 labs. and 44 researchers. In this study, we tried to define a methodol. to assess the reproducibility and trueness of a quant. SERS method and to compare different methods. In our opinion, this is a first important step toward a "standardization" process of SERS protocols, not proposed by a single lab. but by a larger community.
- 548de Albuquerque, C. D. L.; Sobral-Filho, R. G.; Poppi, R. J.; Brolo, A. G. Digital Protocol for Chemical Analysis at Ultralow Concentrations by Surface-Enhanced Raman Scattering. Anal. Chem. 2018, 90, 1248– 1254, DOI: 10.1021/acs.analchem.7b03968548Digital Protocol for Chemical Analysis at Ultralow Concentrations by Surface-Enhanced Raman Scatteringde Albuquerque, Carlos Diego L.; Sobral-Filho, Regivaldo G.; Poppi, Ronei J.; Brolo, Alexandre G.Analytical Chemistry (Washington, DC, United States) (2018), 90 (2), 1248-1254CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Single mol. surface-enhanced Raman spectroscopy (SM-SERS) has the potential to revolutionize quant. anal. at ultralow concns. (<1 nM). However, there are no established protocols to generalize the application of this technique in anal. chem. Here, a protocol for quantification at ultralow concns. using SM-SERS is proposed. The approach aims to take advantage of the stochastic nature of the single-mol. regime to achieved lower limits of quantification (LOQ). Two emerging contaminants commonly found in aquatic environments, enrofloxacin (ENRO) and ciprofloxacin (CIPRO), were chosen as nonresonant mol. probes. The methodol. involves a multivariate resoln. curve fitting known as nonneg. matrix factorization with alternating least-squares algorithm (NMF-ALS) to solve spectral overlaps. The key element of the quantification is to realize that, under SM-SERS conditions, the Raman intensity generated by a mol. adsorbed on a hotspot can be digitalized. Therefore, the no. of SERS event counts (rather than SERS intensities) is proportional to the soln. concn. This allowed the detn. of both ENRO and CIPRO with high accuracy and precision even at ultralow concns. regime. The LOQ for both ENRO and CIPRO were achieved at 2.8 pM. The digital SERS protocol, suggested here, is a roadmap for the implementation of SM-SERS as a routine tool for quantification at ultralow concns.
- 549Wang, W.; Srivastava, S.; Garg, A.; Xiao, C.; Hawks, S.; Pan, J.; Duggal, N.; Isaacman-VanWertz, G.; Zhou, W.; Marr, L. C.; Vikesland, P. J. Digital Surface-Enhanced Raman Spectroscopy–Lateral Flow Test Dipstick: Ultrasensitive, Rapid Virus Quantification in Environmental Dust. Environ. Sci. Technol. 2024, 58, 4926– 4936, DOI: 10.1021/acs.est.3c10311There is no corresponding record for this reference.
- 550Shim, J.-E.; Kim, Y. J.; Choe, J.-H.; Lee, T. G.; You, E.-A. Single-Nanoparticle-Based Digital SERS Sensing Platform for the Accurate Quantitative Detection of SARS-CoV-2. ACS Appl. Mater. Interfaces 2022, 14, 38459– 38470, DOI: 10.1021/acsami.2c07497550Single-Nanoparticle-Based Digital SERS Sensing Platform for the Accurate Quantitative Detection of SARS-CoV-2Shim, Jae-Eul; Kim, Young Jun; Choe, Jong-Ho; Lee, Tae Geol; You, Eun-AhACS Applied Materials & Interfaces (2022), 14 (34), 38459-38470CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)To prevent the ongoing spread of the highly infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), accurate and early detection based on a rapid, ultrasensitive, and highly reliable sensing method is crucially important. Here, we present a bumpy core-shell surface-enhanced Raman spectroscopy (SERS) nanoprobe-based sensing platform with single-nanoparticle (SNP)-based digital SERS anal. The tailorable bumpy core-shell SERS nanoprobe with an internal self-assembled monolayer of 4-nitrobenzenethiol Raman reporters, synthesized using HEPES biol. buffer, generates a strong, uniform, and reproducible SERS signal with an SNP-level sensitive and narrowly distributed enhancement factor (2.1 x 108 to 2.2 x 109). We also propose an SNP-based digital SERS anal. method that provides direct visualization of SNP detection at ultralow concns. and reliable quantification over a wide range of concns. The bumpy core-shell SERS nanoprobe-based sensing platform with SNP-based digital SERS anal. achieves the ultrasensitive and quant. detection of the SARS-CoV-2 spike protein with a limit of detection of 7.1 x 10-16 M over a wide dynamic range from 3.7 x 10-15 to 3.7 x 10-8 M, far outperforming the conventional ELISA method for the target protein. Furthermore, it can detect mutated spike proteins from the SARS-CoV-2 variants, representing the key mutations of Alpha, Beta, Gamma, Delta, and Omicron variants. Therefore, this sensing platform can be effectively and efficiently used for the accurate and early detection of SARS-CoV-2 and be adapted for the ultrasensitive and reliable detection of other highly infectious diseases.
- 551Nam, W.; Kim, W.; Zhou, W.; You, E.-A. A digital SERS sensing platform using 3D nanolaminate plasmonic crystals coupled with Au nanoparticles for accurate quantitative detection of dopamine. Nanoscale 2021, 13, 17340– 17349, DOI: 10.1039/D1NR03691B551A digital SERS sensing platform using 3D nanolaminate plasmonic crystals coupled with Au nanoparticles for accurate quantitative detection of dopamineNam, Wonil; Kim, Wansun; Zhou, Wei; You, Eun-AhNanoscale (2021), 13 (41), 17340-17349CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)We report a digital surface-enhanced Raman spectroscopy (SERS) sensing platform using the arrays of 3D nanolaminate plasmonic crystals (NLPC) coupled with Au nanoparticles and digital (on/off) SERS signal anal. for the accurate quant. detection of dopamine (DA) at ultralow concns. 3D NLPC SERS substrates were fabricated to support the optically dense arrays of vertically-stacked multi-nanogap hotspots and combined with Raman tag-conjugated Au nanoparticles for NLPC-based dual-recognition structures. We demonstrate that the 3D NLPC-based dual-recognition structures including Au nanoparticle-induced addnl. hotspots can enable more effective SERS enhancement through the mol. recognition of DA. For the accurate quantification of DA at ultralow concns., we conducted digital SERS anal. to reduce stochastic signal variation due to various microscopic effects, including mol. orientation/position variation and the spatial distribution of nanoparticle-coupled hotspots. The digital SERS anal. allowed the SERS mapping results from the DA-specific dual-recognition structures to be converted into binary "On/Off" states; the no. of "On" events was directly correlated with low-abundance DA mols. down to 1 pM. Therefore, the digital SERS platform using the 3D NLPC-based dual-recognition structures coupled with Au nanoparticles and digital SERS signal anal. can be used not only for the ultrasensitive, accurate, and quant. detn. of DA, but also for the practical and rapid anal. of various mols. on nanostructured surfaces.
- 552Tuckmantel Bido, A.; Brolo, A. G. Digital SERS Protocol Using Au Nanoparticle-Based Extrinsic Raman Labels for the Determination of SARS-CoV-2 Spike Protein in Saliva Samples. ACS Applied Nano Materials 2023, 6, 15426– 15436, DOI: 10.1021/acsanm.3c01979There is no corresponding record for this reference.
- 553Xu, J.; Xie, L.; Zhu, M.; Xiong, C.; Huang, Q.; Zhang, M.; Ren, B.; Tian, Z.; Liu, G. Rapid Sample Pretreatment Facilitating SERS Detection of Trace Weak Organic Acids/Bases in Simple Matrices. Anal. Chem. 2024, 96, 5968– 5975, DOI: 10.1021/acs.analchem.4c00229There is no corresponding record for this reference.
- 554Liu, C.; Weber, S.; Peng, R.; Wu, L.; Zhang, W.-s.; Luppa, P. B.; Popp, J.; Cialla-May, D. Toward SERS-based therapeutic drug monitoring in clinical settings: Recent developments and trends. TrAC Trends in Analytical Chemistry 2023, 164, 117094, DOI: 10.1016/j.trac.2023.117094There is no corresponding record for this reference.
- 555Markina, N. E.; Goryacheva, I. Y.; Markin, A. V. Sample pretreatment and SERS-based detection of ceftriaxone in urine. Anal. Bioanal. Chem. 2018, 410, 2221– 2227, DOI: 10.1007/s00216-018-0888-y555Sample pretreatment and SERS-based detection of ceftriaxone in urineMarkina, Natalia E.; Goryacheva, Irina Yu.; Markin, Alexey V.Analytical and Bioanalytical Chemistry (2018), 410 (8), 2221-2227CODEN: ABCNBP; ISSN:1618-2642. (Springer)The aim of the work is the development of the procedure for ceftriaxone (antibiotic drug of cephalosporin class) detection in urine using surface-enhanced Raman spectroscopy (SERS). Hydroxylamine stabilized silver nanoparticles were used as SERS-active material. Addnl. urine pretreatment steps were developed to eliminate the influence of creatinine on the ceftriaxone SERS signal. These steps include adjusting of the sample pH to alk. value (pH 13) and purifn. of the sample using silica gel column chromatog. Alkali pH increases SERS signal of ceftriaxone, while silica gel separates the analyte from creatinine-the main admixt. in urine which provides inappropriate SERS signal background. Addnl., total protein content up to 0.2 mg/mL (upper level for urine of healthy person) and pH deviation of initial urine do not influence on SERS signal of ceftriaxone. The proposed detection procedure enables fast (∼ 10 min) detn. of ceftriaxone in artificially spiked urine samples within 5 to 500 μg/mL range of concns. which matches the range of the drug concns. in urine after injection of therapeutically required dosages. Limits of detection (3σ) and quantification (10σ) are 0.4 and 2.0 μg/mL, correspondingly.
- 556Oakley, L. H.; Fabian, D. M.; Mayhew, H. E.; Svoboda, S. A.; Wustholz, K. L. Pretreatment Strategies for SERS Analysis of Indigo and Prussian Blue in Aged Painted Surfaces. Anal. Chem. 2012, 84, 8006– 8012, DOI: 10.1021/ac301814e556Pretreatment Strategies for SERS Analysis of Indigo and Prussian Blue in Aged Painted SurfacesOakley, Lindsay H.; Fabian, David M.; Mayhew, Hannah E.; Svoboda, Shelley A.; Wustholz, Kristin L.Analytical Chemistry (Washington, DC, United States) (2012), 84 (18), 8006-8012CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Surface-enhanced Raman scattering (SERS) spectroscopy is increasingly applied to the identification of org. colorants in cultural heritage objects because vibrational fingerprints can be measured from microscopic samples. However, the development of SERS into a reliable, broad-spectrum method for art anal. requires the study of a wide variety of org. and inorg. colorants as well as colorant mixts. in paint. Here, we demonstrate reliable protocols for SERS-based identification of insol. indigo, Prussian blue (PB), and mixts. thereof in aged painted surfaces. The use of simple salts and acids for sample pretreatment is evaluated. High-quality SERS spectra of PB and indigo are elucidated upon sample pretreatment with H2SO4. In several cases, SERS spectra of the colorants could not be obtained without sample pretreatment. We demonstrate the use of H2SO4 to solubilize PB as well as perform an in situ conversion of insol. indigo to sol. indigo carmine (IC) on indigo, indigo oil paint, and actual samples from historic painted surfaces. A microscopic H2SO4-treated sample from the Portrait of Evelyn Byrd produced a SERS spectrum that is consistent with a mixt. of PB and IC. To our knowledge, this work represents the first SERS spectrum of indigo in oil paint and the first simultaneous detection of a mixt. of blue org. and inorg. colorants in a single art sample using SERS.
- 557Song, C.; Li, J.; Sun, Y.; Jiang, X.; Zhang, J.; Dong, C.; Wang, L. Colorimetric/SERS dual-mode detection of mercury ion via SERS-Active peroxidase-like Au@AgPt NPs. Sens. Actuators, B 2020, 310, 127849, DOI: 10.1016/j.snb.2020.127849557Colorimetric/SERS dual-mode detection of mercury ion via SERS-Active peroxidase-like Au@AgPt NPsSong, Chunyuan; Li, Jinxiang; Sun, Youzhi; Jiang, Xinyu; Zhang, Jingjing; Dong, Chen; Wang, LianhuiSensors and Actuators, B: Chemical (2020), 310 (), 127849CODEN: SABCEB; ISSN:0925-4005. (Elsevier B.V.)The development of mercury ion (Hg2+) probes integrating the ability of facile preliminary evaluation and high-sensitive accurate assay with wide detection range is very important for water pollution prevention and human health. Herein, a novel colorimetric/SERS dual-mode detection of Hg2+ was proposed by using the SERS-active peroxidase-like Au@AgPt NPs. The Au@AgPt NP has hexoctahedral Au nanoparticle core with edges coating by Pt, which shows good SERS activity of Au and enhanced catalyst activity of Pt for designing colorimetric/SERS dual-mode probes. Basing on the colorimetric assay, 5μM-1 mM Hg2+ can be facile obsd. by naked eye and a linear sensing (1μM-100 M μ) with limit of detection (LOD) of 0.52μM was obtained by absorption anal. Besides, a linear calibration curve from 1 nM to 10μM was achieved by SERS with LOD of 0.28 nM. The proposed dual-mode probes with good selectivity and reliability integrate the advantages of facile detection by colorimetric anal. and high-sensitive trace assay by SERS, and possess relatively better performance on sensitivity and detection range in comparison to the previous probes/methods, which can be served as efficient probes for monitoring water quality.
- 558Dinish, U. S.; Song, Z.; Ho, C. J. H.; Balasundaram, G.; Attia, A. B. E.; Lu, X.; Tang, B. Z.; Liu, B.; Olivo, M. Single Molecule with Dual Function on Nanogold: Biofunctionalized Construct for In Vivo Photoacoustic Imaging and SERS Biosensing. Adv. Funct. Mater. 2015, 25, 2316– 2325, DOI: 10.1002/adfm.201404341558Single Molecule with Dual Function on Nanogold: Biofunctionalized Construct for In Vivo Photoacoustic Imaging and SERS BiosensingDinish, U. S.; Song, Zhegang; Ho, Chris Jun Hui; Balasundaram, Ghayathri; Attia, Amalina Binte Ebrahim; Lu, Xianmao; Tang, Ben Zhong; Liu, Bin; Olivo, MaliniAdvanced Functional Materials (2015), 25 (15), 2316-2325CODEN: AFMDC6; ISSN:1616-301X. (Wiley-VCH Verlag GmbH & Co. KGaA)Multimodal imaging provides complimentary information that is advantageous in studying both cellular and mol. mechanisms in vivo, which has tremendous potential in pre-clin. research and clin. translational imaging. It is desirable to design probes for multimodal imaging that can be administered minimally but provides multifaceted information. Herein, the authors demonstrate the complimentary dual functional ability of a nanoconstruct for mol. imaging in both photoacoustic (PA) and surface-enhanced Raman scattering (SERS) biosensing simultaneously in tandem. To realize this, a group of NIR active org. mols. are designed and synthesized that possess both SERS and PA activity. Nanoconstructs realized by anchoring such mols. onto gold nanoparticles are demonstrated for targeting cancer biomarkers in vivo while providing complimentary information about biodistribution and targeting efficiency. In future, such nanoconstructs could play a major role in identifying surgical margins and also for disease monitoring in translational medicine.
- 559Kenry; Nicolson, F.; Clark, L.; Panikkanvalappil, S. R.; Andreiuk, B.; Andreou, C. Advances in Surface Enhanced Raman Spectroscopy for in Vivo Imaging in Oncology. Nanotheranostics 2022, 6, 31– 49, DOI: 10.7150/ntno.62970There is no corresponding record for this reference.
- 560Xu, J.; Zhang, B.; Zhang, Y.; Mai, L.; Hu, W.; Chen, C.-J.; Liu, J.-T.; Zhu, G. Recent advances in disease diagnosis based on electrochemical-optical dual-mode detection method. Talanta 2023, 253, 124037, DOI: 10.1016/j.talanta.2022.124037560Recent advances in disease diagnosis based on electrochemical-optical dual-mode detection methodXu, Jiaqi; Zhang, Bo; Zhang, Yao; Mai, Luyu; Hu, Wenhao; Chen, Ching-Jung; Liu, Jen-Tsai; Zhu, GuixianTalanta (2023), 253 (), 124037CODEN: TLNTA2; ISSN:0039-9140. (Elsevier B.V.)A review. The electrochem. method is commonly applied in diagnosing and monitoring diseases. When used in conjunction with optical disease detection systems, it can broaden the detection range, lower the limit of detection and create mutual confirmation. Utilizing the electrochem.-optical dual-mode detection method for disease diagnosis is non-invasive, low-cost, easy-to-use, efficient and accurate compared with the traditional single-mode method. This paper reviews the reports of electrochem. and optical methods combined in recent years, such as colorimetry, fluorescence, Surface Enhanced Raman Spectroscopy (SERS), surface plasmon resonance (SPR) and spectroelectrochem. We cover researches on several electrochem.-optical dual-mode detection methods for identifying disease markers, including biochem., cancer, infection, cardiovascular and cerebrovascular disease, and neurol. diseases as well. These studies demonstrate the feasibility of electrochem.-optical dual-mode detection and its broad application prospects in the field of disease detection.
- 561Li, M.; Lin, H.; Paidi, S. K.; Mesyngier, N.; Preheim, S.; Barman, I. A Fluorescence and Surface-Enhanced Raman Spectroscopic Dual-Modal Aptasensor for Sensitive Detection of Cyanotoxins. ACS Sens. 2020, 5, 1419– 1426, DOI: 10.1021/acssensors.0c00307561A Fluorescence and Surface-Enhanced Raman Spectroscopic Dual-Modal Aptasensor for Sensitive Detection of CyanotoxinsLi, Ming; Lin, Hangduo; Paidi, Santosh Kumar; Mesyngier, Nicolas; Preheim, Sarah; Barman, IshanACS Sensors (2020), 5 (5), 1419-1426CODEN: ASCEFJ; ISSN:2379-3694. (American Chemical Society)The ability to detect trace analytes without necessitating solid surface attachment or complicated processing steps would facilitate the translation of sensors for monitoring environmental toxins in the field. To address a crit. unmet need in fresh water ecol., we have developed a dual-modal aptamer-based biosensor (aptasensor), featuring fluorescence and surface-enhanced Raman spectroscopy (SERS), for sensitive and selective detection of hepatotoxin microcystin-LR (MC-LR). The rational sensor design is based on the high affinity of the cyanine (Cy3) dye-modified complementary DNA (Cy3-cDNA) strand toward the plasmonic gold nanostars (GNSs) in comparison to the Cy3-cDNA/aptamer duplex. The preferential binding of MC-LR toward the MC-LR-specific aptamer triggers the dissocn. of Cy3-cDNA/aptamer duplexes, which switches the Cy3's fluorescence "off" and SERS "on" due to the proximity of Cy3 dye to the GNS surface. Both fluorescence and SERS intensities are obsd. to vary linearly with the MC-LR concn. over the range of investigation. We have achieved high sensitivity and excellent specificity with the aptasensor toward MC-LR, which can be attributed to the fluorescence quenching effect, significant SERS enhancement by the GNSs, and the high affinity of the aptamer toward the MC-LR analytes. We further demonstrate the applicability of the present aptasensor for detection of MC-LR in a diverse set of real water samples with high accuracy and excellent reproducibility. With further refinement, we believe that the aptamer-driven complementary assembly of the SERS and fluorescence sensing constructs can be applied for rapid, multiplexed, and robust measurements of environmental toxins in the field.
- 562Jeanmaire, D. L.; Van Duyne, R. P. Surface raman spectroelectrochemistry: Part I. Heterocyclic, aromatic, and aliphatic amines adsorbed on the anodized silver electrode. Journal of Electroanalytical Chemistry and Interfacial Electrochemistry 1977, 84, 1– 20, DOI: 10.1016/S0022-0728(77)80224-6562Surface Raman spectroelectrochemistry. Part I. Heterocyclic, aromatic, and aliphatic amines adsorbed on the anodized silver electrodeJeanmaire, David L.; Van Duyne, Richard P.Journal of Electroanalytical Chemistry and Interfacial Electrochemistry (1977), 84 (1), 1-20CODEN: JEIEBC; ISSN:0022-0728.The remarkable sensitivity of Raman spectroscopy was verified for the study of adsorbed pyridine on a Ag surface, and its applicability extended to other N heterocycles and amines. New bands in the scattering spectrum of adsorbed pyridine were characterized, which were not previously reported, as well as the Raman intensity response of all the surface pyridine bands as a function of electrode potential. As a result of these expts., a model is proposed of the adsorbed species for pyridine in which the adsorption is anion induced, leading to an axial end-on attachment to the electrode surface. The ability to obtain resonance Raman spectra with good signal-to-noise ratios with laser powers < 1.0 mW, opens up possibilities of surface Raman studies with relatively inexpensive laser systems. As laser power requirements are relaxed, reliability is improved, and greater tuning ranges can be achieved for wavelength dependent studies. The potential of resonance Raman spectroscopy was previously demonstrated for monitoring soln. kinetic behavior; now it is shown that normal Raman as well as resonance Raman spectroscopy have sufficient sensitivity to extend the studies of kinetic processes to include those occurring at electrode surfaces.
- 563Brosseau, C. L.; Colina, A.; Perales-Rondon, J. V.; Wilson, A. J.; Joshi, P. B.; Ren, B.; Wang, X. Electrochemical surface-enhanced Raman spectroscopy. Nat. Rev. Methods Prim. 2023, 3, 79, DOI: 10.1038/s43586-023-00263-6There is no corresponding record for this reference.
- 564Markin, A. V.; Arzhanukhina, A. I.; Markina, N. E.; Goryacheva, I. Y. Analytical performance of electrochemical surface-enhanced Raman spectroscopy: A critical review. TrAC Trends in Analytical Chemistry 2022, 157, 116776, DOI: 10.1016/j.trac.2022.116776There is no corresponding record for this reference.
- 565Gu, X.; Wang, K.; Qiu, J.; Wang, Y.; Tian, S.; He, Z.; Zong, R.; Kraatz, H.-B. Enhanced electrochemical and SERS signals by self-assembled gold microelectrode arrays: A dual readout platform for multiplex immumoassay of tumor biomarkers. Sens. Actuators, B 2021, 334, 129674, DOI: 10.1016/j.snb.2021.129674565Enhanced electrochemical and SERS signals by self-assembled gold microelectrode arrays: A dual readout platform for multiplex immumoassay of tumor biomarkersGu, Xuefang; Wang, Kaiyue; Qiu, Jiawei; Wang, Yajie; Tian, Shu; He, Zhenkuan; Zong, Ran; Kraatz, Heinz-BernhardSensors and Actuators, B: Chemical (2021), 334 (), 129674CODEN: SABCEB; ISSN:0925-4005. (Elsevier B.V.)In this study, a dual readout biosensor is reported that combines electrochem. and surface-enhanced Raman scattering (SERS) for a multiplexed immunoassay of tumor biomarkers. A gold microelectrode array (GMA) was fabricated by electrodeposition of Au to the bottom of numerous individual silica cavities. Electrochem. studies demonstrate that the GMA possesses unique charge selectivity and an inherently high S/N ratio, which make the GMA esp. suitable for differential pulse voltammetry (DPV) and square wave voltammetry (SWV) detection. Hybridization chain reaction (HCR) was designed to increase the load of labeled mols. in this super-sandwich structured biosensor. Meanwhile, the strong plasmon coupling between silver nanoparticles and the underlying gold particles enabled ultrahigh sensitivity of the GMA when using SERS readout. By combining electrochem. and SERS methods, we achieved the high-throughput preliminary screening of alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA). Further quant. anal. showed that the two proteins could be detd. in a wide concn. range, and their min. detection limits were 0.6 and 0.3 pg·mL-1 when using SERS method, resp. The applicability of the proposed dual readout platform in clin. diagnosis was verified by the detection in human serum samples.
- 566SPELEC Raman Electrochemistry. Metrohm. https://www.metrohm.com/en/products/electrochemistry/spelec-spectroelectrochemistry/SPELECRAMAN.There is no corresponding record for this reference.
- 567Sardar, S.; Fabris, L.; Javanmard, M. Improved Precision in Surface-Enhanced Raman Scattering Quantification of Analyte through Dual-Modality Multisite Sensing. Anal. Chem. 2019, 91, 4323– 4330, DOI: 10.1021/acs.analchem.8b02559567Improved Precision in Surface-Enhanced Raman Scattering Quantification of Analyte through Dual-Modality Multisite SensingSardar, Sakshi; Fabris, Laura; Javanmard, MehdiAnalytical Chemistry (Washington, DC, United States) (2019), 91 (7), 4323-4330CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)Accurate quantification of analyte using surface-enhanced Raman spectroscopy (SERS) is a desired, yet unfulfilled, ability that could enable a plethora of diagnostic- and defense-related applications. The major hurdles to overcome to achieve this goal are expensive manufg. for highly ordered and reproducible substrates and low reproducibility of substrates produced through low cost methods. A technol. that can set industry stds. for manufg./processing of SERS substrates is still yet to be achieved. A dual-modality multisite sensing approach was developed, that overcomes the limitations experienced when fabricating bottom-up, reproducible, sensitive, and low-cost SERS substrates. Electrochem. was combined with SERS for dual-modality sensing to improve precision by adding redundancy and encoding features, thus increasing measurement robustness and predictability. This technique works by calibrating SERS response with respect to active surface area, a parameter known to be proportional to charge, which can be estd. via electrochem. measurements. The dual-modality multisite measurement demonstrates at least 2.8× improvement in assay precision compared to the traditional single-site Raman measurements. The technique yields overall improved precision of measurement and is not limited to any particular SERS substrate or geometry, and thus it can be adapted and incorporated readily in any SERS sensing assay.
- 568Fabris, L. Bottom-up optimization of SERS hot-spots. Chem. Commun. 2012, 48, 9346– 9348, DOI: 10.1039/c2cc34068b568Bottom-up optimization of SERS hot-spotsFabris, LauraChemical Communications (Cambridge, United Kingdom) (2012), 48 (75), 9346-9348CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)The bottom-up optimization of signal-to-noise ratios for SERS tags employing SAMSA fluorescein as the reporter was achieved using a bifunctional linker with low Raman cross section. By holding the nanoparticles at sub-nm sepn., the linker allowed one to optimize the hot-spot thereby significantly reducing the fluorescence background.
- 569Dardir, K.; Wang, H.; Martin, B. E.; Atzampou, M.; Brooke, C. B.; Fabris, L. SERS Nanoprobe for Intracellular Monitoring of Viral Mutations. J. Phys. Chem. C 2020, 124, 3211– 3217, DOI: 10.1021/acs.jpcc.9b09253569SERS Nanoprobe for Intracellular Monitoring of Viral MutationsDardir, Kholud; Wang, Hao; Martin, Brigitte E.; Atzampou, Maria; Brooke, Christopher B.; Fabris, LauraJournal of Physical Chemistry C (2020), 124 (5), 3211-3217CODEN: JPCCCK; ISSN:1932-7447. (American Chemical Society)Gold nanostars, functionalized with thiolated DNA hairpins bearing a Raman-active fluorescent dye at the 3' terminus, were engineered to identify and quantify RNA mutations in the influenza A virus (IAV) genome employing surface enhanced Raman spectroscopy (SERS). The DNA hairpin structure was designed to selectively extend/fold in the absence/presence of the viral RNA targets, resulting in the fluorophore being brought away from or close to the gold nanostar surface, leading to an "OFF-ON" switching of the SERS signal. Validation of the switchable SERS nanostar probes was first carried out in buffer, showing that the detection is sequence-specific and that the high sensitivity provided by these SERS probes allows target detection at the single particle level. We also demonstrate that the degree of signal recovery can be closely correlated with the no. of genetic mutations. Further expts. carried out with HeLa cell lysate spiked with RNA oligonucleotides demonstrate that the functionality of these nanoprobes were not detrimentally affected by the complex matrix. As a proof of concept, we also tested these nanoparticle probes in vitro by specifically targeting the hemagglutinin (HA) segment in live HeLa cells transfected with plasmids coding for either HA or two other IAV segments, PB1 and PB2, as neg. controls. The intracellular SERS response in individual transfected HeLa cells demonstrates high sequence-selectivity of the probes for the HA segment, suggesting the applicability of these probes for multiplexed detection and quantification of viral RNAs in individual cells with an approach that can account for the viral population diversity. This also represents the first time that mol. beacon-based SERS probes have been employed to detect viral RNA target in intact individual cells.
- 570Wang, H.; Dardir, K.; Lee, K. B.; Fabris, L. Impact of Protein Corona in Nanoflare-Based Biomolecular Detection and Quantification. Bioconjugate Chem. 2019, 30, 2555– 2562, DOI: 10.1021/acs.bioconjchem.9b00495570Impact of Protein Corona in Nanoflare-Based Biomolecular Detection and QuantificationWang, Hao; Dardir, Kholud; Lee, Ki-Bum; Fabris, LauraBioconjugate Chemistry (2019), 30 (10), 2555-2562CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)Selective detection and precise quantification of biomols. in intracellular settings play a pivotal role in the diagnostics and therapeutics of diseases, including various cancers and infectious epidemics. Because of this clin. relevance, nanoprobes with high sensitivity, wide tunability, and excellent biol. stability have become of high demand. In particular, nanoflares based on gold nanoparticles have emerged as an attractive candidate for intracellular detection due to their efficient cellular uptake, enhanced binding affinity with complementary targets, and improved biol. compatibility. However, nanoprobes, including these nanoflares, are known to be susceptible to the adsorption of proteins present in the biol. environment which leads to the formation of a so-called protein corona layer on their surface, leading to an altered targeting efficiency and cellular uptake. In this work, the authors leverage the nanoflares platform to demonstrate the effect of protein corona on biomol. detection, quantification, as well as biol. stability against enzymic degrdn. Nanoflares incubated in a biol. relevant concn. of serum albumin proteins (0.50%) were shown to result in more than 20% signal redn. in target detection, with a decrease varying proportionally with the protein concns. In addn., similar signal redn. was obsd. for different serum proteins, and PEG backfilling was found to be ineffective in mitigating the neg. impact induced by the corona formation. Furthermore, nuclease resistance in nanoflares was also severely compromised by the presence of the corona shell (∼ 2 folds increase in hydrolysis activity). This work demonstrates the consequences of an in-situ formed protein corona layer on mol. detection/quantification and biol. stability of nanoflares in the presence of nuclease enzymes, highlighting the importance of calibrating similar nanoprobes in proper biol. media to improve the accuracy of mol. detection and quantification.
- 571Bhamidipati, M.; Cho, H. Y.; Lee, K. B.; Fabris, L. SERS-Based Quantification of Biomarker Expression at the Single Cell Level Enabled by Gold Nanostars and Truncated Aptamers. Bioconjugate Chem. 2018, 29, 2970– 2981, DOI: 10.1021/acs.bioconjchem.8b00397571SERS-Based Quantification of Biomarker Expression at the Single Cell Level Enabled by Gold Nanostars and Truncated AptamersBhamidipati, Manjari; Cho, Hyeon-Yeol; Lee, Ki-Bum; Fabris, LauraBioconjugate Chemistry (2018), 29 (9), 2970-2981CODEN: BCCHES; ISSN:1043-1802. (American Chemical Society)Surface-enhanced Raman spectroscopy (SERS)-based biosensors have been used increasingly over the past few years for cancer detection and diagnosis. SERS-based imaging offers excellent sensitivity and has advantages over other detection techniques such as fluorescence. The authors developed a novel biosensor to detect the cancer biomarker epithelial cell adhesion mol. (EpCAM) and quantify its expression at the single cell level. EpCAM is one of the most commonly expressed markers on a variety of cancer cells; importantly it has been suggested that redn. of its expression levels could be assocd. with the epithelial to mesenchymal transition (EMT) and thus to the onset of metastasis. Therefore, monitoring variations in expression levels of this membrane biomarker would improve the authors' ability to monitor cancer progression. The described substrate-based biosensor was developed employing gold nanostars functionalized with EpCAM aptamer mols. and was able to quantify subnanomolar concns. of EpCAM protein in soln. Importantly, the authors demonstrated its use to quantify EpCAM expression on the surface of two cancer cells, MCF-7 and PC-3. The authors also compared the binding efficiency of two EpCAM DNA aptamers of different lengths and obsd. a substantial improvement in the sensitivity of detection by employing the shorter aptamer sequence, probably due to the reduced no. of conformations possible at room temp. with the truncated oligonucleotide. Detailed characterization of the substrates was carried out using both SERS maps and at. force microscopy. These substrate-based diagnostic devices promise to be relevant for monitoring phenotype evolutions in cancer cells, blood, and other bodily fluids, thus improving the authors' ability to follow in real time disease onset and progression.
- 572Bhamidipati, M.; Lee, G.; Kim, I.; Fabris, L. SERS-Based Quantification of PSMA in Tissue Microarrays Allows Effective Stratification of Patients with Prostate Cancer. ACS Omega 2018, 3, 16784– 16794, DOI: 10.1021/acsomega.8b01839572SERS-Based Quantification of PSMA in Tissue Microarrays Allows Effective Stratification of Patients with Prostate CancerBhamidipati, Manjari; Lee, Geuntaek; Kim, Isaac; Fabris, LauraACS Omega (2018), 3 (12), 16784-16794CODEN: ACSODF; ISSN:2470-1343. (American Chemical Society)Prostate specific membrane antigen (PSMA), a type II membrane protein, is an attractive biomarker that has been validated clin. for the diagnosis of prostate cancer. The authors developed SERS nanoprobes for PSMA detection and quantification at the single cell level on prostate cancer cells. The cells were targeted employing SERS nanoprobes that consisted of gold nanostars functionalized with PSMA aptamer mols. The authors were able to quantify picomolar concns. of sol. PSMA protein and used the resulting calibration curve to est. the expression of PSMA on the surface of the prostate cancer cell, LNCaP, at the single cell level. Importantly, the authors employed these SERS tags to stratify prostate cancer patients by assessing PSMA expression in tissues contained in a prostate tissue microarray. The stratification results clearly correlated PSMA expression to recommended therapy groups, rendering the described method an effective tool to aid in designing personalized therapeutic protocols. Benchmarking detection sensitivity against immunofluorescence staining and comparing stratification results obtained with the two methods allowed the authors to validate the authors' novel approach against std. practices. Based on these results, the authors confirm the validity of PSMA as an effective biomarker for prostate cancer patient evaluation and propose SERS-based diagnostic techniques as integrative methods for the assessment of disease stage and the identification of effective th