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LetterMarch 4, 2025

DNA Sensing with Whispering Gallery Mode Microlasers
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Soraya Caixeiro*
Soraya Caixeiro
Department of Chemistry and Biochemistry, Humboldt Centre for Nano- and Biophotonics, Institute for Light and Matter, Greinstrasse 4-6, 50939 Cologne, Germany
Centre for Photonics and Photonic Materials, Department of Physics, University of Bath, Bath BA2 7AY, United Kingdom
*[email protected]
More by Soraya Caixeiro
https://orcid.org/0000-0003-4605-957X
Robert Dörrenhaus
Robert Dörrenhaus
Department of Chemistry and Biochemistry, Institute of Organic Chemistry, Greinstrasse 4, 50939 Cologne, Germany
More by Robert Dörrenhaus
https://orcid.org/0009-0006-4685-9939
Anna Popczyk
Anna Popczyk
Department of Chemistry and Biochemistry, Humboldt Centre for Nano- and Biophotonics, Institute for Light and Matter, Greinstrasse 4-6, 50939 Cologne, Germany
More by Anna Popczyk
Marcel Schubert
Marcel Schubert
Department of Chemistry and Biochemistry, Humboldt Centre for Nano- and Biophotonics, Institute for Light and Matter, Greinstrasse 4-6, 50939 Cologne, Germany
More by Marcel Schubert
Stephanie Kath-Schorr*
Stephanie Kath-Schorr
Department of Chemistry and Biochemistry, Institute of Organic Chemistry, Greinstrasse 4, 50939 Cologne, Germany
*[email protected]
More by Stephanie Kath-Schorr
https://orcid.org/0000-0002-5180-360X
Malte C. Gather*
Malte C. Gather
Department of Chemistry and Biochemistry, Humboldt Centre for Nano- and Biophotonics, Institute for Light and Matter, Greinstrasse 4-6, 50939 Cologne, Germany
Centre of Biophotonics, SUPA School of Physics and Astronomy, University of St Andrews, St Andrews KY16 9SS, United Kingdom
*[email protected]
More by Malte C. Gather
https://orcid.org/0000-0002-4857-5562

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Nano Letters

Cite this: Nano Lett. 2025, 25, 11, 4467–4475

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https://doi.org/10.1021/acs.nanolett.5c00078

Published March 4, 2025

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Abstract

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Nucleic acid sensing is crucial for advancing diagnostics, therapeutic monitoring, and molecular biology research by enabling the precise identification of DNA and RNA interactions. Here, we present an innovative sensing platform based on DNA-functionalized whispering gallery mode (WGM) microlasers. By correlating spectral shifts in laser emission to changes in the refractive index, we demonstrate real-time detection of DNA hybridization and structural changes. The addition of gold nanoparticles to the DNA strands significantly enhances sensitivity, and exclusively labeling the sensing strand or a hairpin strand eliminates the need for secondary labeling of the target strand. We further show that ionic strength influences DNA compactness, and we introduce a hairpin-based system as a dual-purpose sensor and controlled release mechanism for drug delivery. This versatile WGM-based platform offers promise for sequence-specific nucleic acid sensing, multiplexed detection, and in vivo applications in diagnostics and cellular research.

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Keywords

Nucleic acid chemistry is a fast-growing field with major implications for diagnostic and therapeutic applications as well as materials science. (1−3) A comprehensive understanding of the structure and dynamics of DNA and RNA is essential for a better understanding of their functions and for deeper insight into their mechanisms of action. (4) In addition to the formation of double-stranded DNA helices, the diverse folding of RNA or single-stranded DNA (ssDNA) and the dynamic changes in their structures under different conditions are essential for the function of nucleic acids. (5−7) In particular, oligonucleotide-based sensors are an expanding field of research and have proven to be a groundbreaking tool for prognosis and diagnosis. (8−14)

Lasers are well suited for enhancing the sensitivity of a wide range of measurements, primarily due to their narrow emission spectra resulting from stimulated emission. These properties are sometimes overlooked, and lasers are often used simply as a bright, directed, and narrow band excitation source for various applications, including excitation of fluorescence, Raman, surface plasmon resonance, and others. Instead, lasers can also be employed as sensors in their own right, (15−17) e.g., when their spectrum is used as a highly accurate external spectral ruler that shifts (18,19) and changes in intensity (20−22) through interaction of the laser with an analyte. This variant of laser-based sensing benefits considerably from the ability to make microscopic (volume of ≪50 μm³), low-cost, robust, and biocompatible lasers. In this context, the use of whispering gallery mode (WGM) lasers is particularly attractive. WGM lasers often operate by optical pumping of dye molecules embedded in an otherwise transparent microsphere, made, for instance, of polystyrene, and rely on the optical confinement of the resulting emission inside the microsphere due to a refractive index (RI) contrast with the environment. Over the past decade, there has been a quickly growing body of work where such lasers have been directly integrated with biological matter, e.g., for tracking of cell migration (23−25) and sensing cellular forces, (26,27) the latter even including noncontact measurements of local contractility in the living heart. (19) Looking at laser-based DNA sensing, double-stranded DNA (dsDNA) intercalated with a fluorescent dye has been employed both as a laser gain medium (28) and as a sensing conduit, with sensing activated through staining after the DNA is hybridized, a process that occurs only when the base pairs between the strands match. (29)

Gold nanoparticles (Au NPs) have a wide range of applications in optics, catalysis, biomedicine, and sensing, owing to their controllable physiochemical properties, high chemical stability, good biocompatibility, and excellent accessibility by wide-ranging surface functionalization. (30−32) These unique characteristics make Au NPs valuable for sensing applications involving variations in interactions between nanoparticles with differences in parameters such as particle type, shape, relative position, and number of particles (33,34) or even by assembling Au NPs with DNA to build complex structures with target-tailored functionalities. (35,36) Polystyrene microspheres coated with Au NPs have been used to sense viral DNA using a fluorescently labeled single-stranded (ssDNA) capture oligonucleotide; this method relies on a fluorescently labeled ssDNA capture oligonucleotide, where fluorescence quenching occurs upon hybridization with the target DNA. (8)

Beyond fluorescence-based sensing, Au NPs have also been used to locally enhance the electric field, therby improving WGM-based detection of DNA. (37−39) Their ability to concentrate electromagnetic fields at the nanoscale enhances optical signals, increasing the sensitivity of the biosensors. Over the past few decades, techniques for detecting short oligonucleotide sequences through in situ hybridization have expanded considerably. (8,40−42)

Here, to gain insight into the structure and dynamics of oligonucleotides, we developed a novel method for sensing structural changes in DNA immobilized on a WGM microlaser that uses the minute local variation in RI caused by these structural changes. This approach exploits the unique optical properties of WGM microlasers and their ability to measure external RI. We further enhance the sensitivity of our measurement by the addition of Au NPs to the DNA, which allows for the specific sensing of short DNA fragments.

In the example used in this study, the probe is based on a green-emitting, polystyrene-based WGM microlaser that is functionalized with ssDNA. Our model system consists of complementary strand DNA (csDNA) strands and DNA hairpin-forming strands. The polystyrene microlaser is covalently bound via a short linker to the strained cyclooctyne (SCO)-PEG3--modified 3′-end of an ssDNA sequence, which is modified with an amino group on its 5′-end and bound to a 2.2 nm diameter Au NP. Hybridization with csDNA leads to an increase of the RI in the immediate vicinity of the microlaser. This increase can be detected reliably through ensemble experiments on multiple lasers or via live analysis of an individual laser; the latter also provides insights into the hybridization dynamics. Moreover, we have developed a test system for a cleavable hairpin-based carrier that releases its Au NP only after the detection of specific DNA fragments.

In the future, with further investigation, our method could be adapted to detect the dynamics of ssDNA folding or to indicate hybridization or denaturation under different conditions. Our platform is highly versatile and can be adapted to detect different sequences of interest. Taken together, these characteristics make DNA-functionalized WGM lasers valuable tools for various applications in DNA sensing and analysis.

The WGM microlasers used in this study are commercially available, monodisperse fluorescent polystyrene (PS) microspheres, approximately 11 μm in diameter, featuring carboxyl groups on their surface for functionalization with ssDNA, and containing a green-emitting fluorescent dye dispersed within the PS matrix. The DNA sequences used are provided in Table S1. In brief, these sequences consist of a 22-base sequence modified at the 5′-end with an amine group for coupling to the carboxyl groups on the WGM microlasers or on Au NPs. Modifications at the 3′-end varied; some sequences were left unmodified, while others were conjugated with SCO-PEG3 for Au NP attachment or tagged with Cy5 dye for conjugation confirmation (see Figure S1).

Carboxyl groups on both the microlasers and the Au NPs were activated using carbodiimide chemistry, facilitating the formation of amide bonds with the amine-modified DNA. To prevent nonspecific binding, ethanolamine was used to block unreacted carboxyl groups. The DNA was then conjugated either to the Au NPs or directly to the microlasers.

To conjugate Au NPs, the Au NPs were covalently bound to the amino modification on the DNA’s 5′-end and the microlasers were first modified with 11-azido-3,6,9-trioxaundecan-1-amine, allowing the strain-promoted alkyne azide cycloaddition reaction (SPAAC) with the SCO-PEG3-terminated modified DNA, as described in the section 2 of the Supporting Information and illustrated in Figure 1a.

Figure 1. Preparation and optical characterization of the surface coating with gold nanoparticle (Au NP)-functionalized DNA on microlasers. (a) Schematic of the nanoparticle ssDNA conjugation to a carboxyl-functionalized microlaser. (b) Electron microscopy image of a carboxyl-functionalized microlaser. The scale bar is 2 μm. (c) Electron microscopy image of a microlaser decorated with DNA functionalized with 40 nm diameter Au NPs. Scale bars are 2 μm and 500 nm (inset). (e) Green fluorescence from a microlaser functionalized with ssDNA with Cy5 dye. (f) Red fluorescence of same microlaser. (g) Overlay of green and red emission. (h–j) Microlaser with dye-free ssDNA on the surface showing no red fluorescence (h). The hybridization with csDNA containing Cy5 illustrated in panel i leads to the appearance of a red ring in the fluorescence image (j). Scale bars for panels e–h and j are 20 μm.

To confirm successful modification of the microlaser surfaces with ssDNA, ssDNA tagged with the fluorescent dye Cy5 at its 3′-end was conjugated to the microlaser surface. Cy5 was selected for its red emission, which is well-separated from the absorption and emission spectra of the microlasers. Panels e–g of Figure 1 show the green fluorescence from the microlasers, the red fluorescence from ssDNA conjugated to its surface, and an overlay of the two images, respectively. The clearly visible fluorescent ring at the microlaser surface confirms the successful conjugation of ssDNA.

To confirm the modification of ssDNA strands with Au NPs and their subsequent attachment to the microlasers, we used 40 nm diameter Au NPs. This size was chosen for its ease of visualization using scanning electron microscopy (SEM), as detailed in section 2.6 of the Supporting Information. (Due to their small size and resolution limitations, 2.2 nm Au NPs were not visible via SEM, as shown in Figure S2.) All subsequent work used Au NPs with a diameter of 2.2 nm to avoid influencing DNA folding by NPs that are large compared to the DNA duplexes used, which have a calculated length of 6.6 nm for B-DNA duplexes. Figure 1b shows an SEM image of the smooth surface of an unmodified, carboxylated microlaser, while Figure 1c depicts a microlaser surface decorated with ssDNA conjugated with 40 nm Au NPs; a further magnified image is provided in Figure S3.

As further evidence for successful NP functionalization, we look at the addition of ssDNA conjugated with 40 nm Au NPs to a solution of azide-modified microlasers. Initially, the solution appeared red (Figure 1d, left tube) due to the plasmon resonance of the Au NPs dispersed in the solution. After 3 h, most of the NP-conjugated ssDNA has reacted with the microlasers, which precipitated to the bottom of the container due to their size and weight. As a result, the solution became nearly transparent (Figure 1d, right tube).

Lastly, csDNA was introduced, matching the sequence of ssDNA conjugated to the microlaser surface. To confirm conjugation, microlasers previously modified with the ssDNA were reacted with csDNA that was conjugated with Cy5 on its 3′-end (Figure 1i). While microlasers conjugated with ssDNA alone showed minimal red fluorescence (Figure 1h), there was a distinct ring-like emission on the surface after reaction with csDNA (Figure 1j), confirming successful hybridization to dsDNA.

The fluorescent molecules embedded within the PS microspheres can provide optical gain. When pumped with pulsed laser light above a threshold energy density of approximately 125 μJ/cm², as established by previous studies, (18) the microspheres therefore emit laser light, and their emission spectra are dominated by a series of WGM lasing peaks. The emission spectrum of the lasers is characterized by a series of sharp peaks associated with alternating transverse-electric (TE) and transverse-magnetic (TM) modes, where the electric field of the light in the WGM is oriented either parallel (TE) or perpendicular (TM) to the surface. The exact wavelength of these peaks strongly depends on both the microlaser size and the RI in the immediate vicinity of the laser. A typical experimentally observed lasing spectrum is shown in Figure 2a. Panels b and c of Figure 2 show simulated emission spectra for a microlaser embedded in two media with different RIs (details on how these spectra were generated can be found in section 2.7 of the Supporting Information). For the medium with a higher RI, a red-shift in the positions of all peaks/modes is observed. By carefully analyzing the modal positions and knowing the internal RI of the microlaser, we were able to determine both the microlaser size and the external RI, following a routine described, e.g., in ref (43). Using this approach, the external RI for the microlaser in Figure 2a is determined to be 1.339.

Figure 2. Refractive index sensing of DNA surface modifications. (a) Representative lasing spectra from a microlaser in a buffered solution, along with the fitted refractive index. (b) Simulated lasing spectra for microlasers embedded in media of two different refractive indices: n = 1.340 (orange), and n = 1.345 (blue). (c) Close-up of the simulated spectra, highlighting the spectral shifts across different refractive indices and polarization, for azimuthal mode number m = 105. Histograms of external refractive indices calculated from measured laser spectra, with a corresponding box plot, showing (d) carboxyl-functionalized microlasers (N = 71), (e) microlasers conjugated with ssDNA (N = 99), (f) microlasers conjugated with dsDNA (N = 90), (g) microlasers conjugated with ssDNA and Au NPs (N = 65), and (h) microlasers conjugated with dsDNA and Au NPs (N = 91). The illustrations to the right of each histogram depict the configuration for each case.

Panels d–h of Figure 2 summarize the external RI for N > 40 microlasers for each successive step of surface functionalization, measured in the same buffered solution, clearly demonstrating a trend of increasing RI. As expected, the carboxylated microlasers exhibit the lowest external RI (Figure 2d), serving as the baseline for later modifications. Upon addition of ssDNA, we observe a modest increase in the mean external RI of just 0.0013 RIU, slightly smaller than the standard deviation of the mean, which is around 0.002 RIU and not statistically significant (Figure 2e). Similarly, the transition from ssDNA to helical B-form dsDNA through hybridization does not produce a statistically significant change in the RI (Figure 2f), suggesting that the structural alterations associated with hybridization are not captured within the resolution limit of the ensemble measurement.

A more pronounced effect is observed when ssDNA is conjugated with Au NPs at the 5′-end; in this scenario, the RI increases by 0.004 RIU (Figure 2g) compared to ssDNA without Au NPs and by 0.005 RIU compared to the bare carboxylated microlasers, resulting in statistically significant differences in RI distributions (p < 0.05). The larger standard deviation of 0.004 RIU likely reflects increased sample heterogeneity.

Compared to our initial experiment with unmodified DNA, the RI change from ssDNA-Au NPs to dsDNA-Au NPs conjugates is relatively small but statistically significant (p < 0.05), with an average increase of 0.002 RIU (Figure 2h). Overall, these results demonstrate that the attachment of Au NPs is important for producing measurable and significant changes in the external RI upon DNA binding to microlasers.

WGM modes decay exponentially away from the surface of the microlasers or resonators; (44) for the resonator geometry described here, the 1/e extension for a typical TE mode is approximately 120 nm. (18) The observed increase in the average external refractive index is influenced by the full extension, with the highest sensitivity occurring near the surface, where the field overlap is strongest.

Thus, the refractive index measurement does not represent the intrinsic refractive index of DNA or Au NPs alone but rather their combined effect with the buffer medium. When the DNA helix forms, bringing Au NPs closer to the surface, the increased overlap with the evanescent field leads to a higher measured RI.

Next, we examined how the ionic strength and buffer concentration affect the RI measured by microlasers. Microlasers modified with ssDNA-Au NPs were hybridized with complementary csDNA in buffers of varying concentrations. Since the buffer concentration correlates with ionic strength, this approach enabled us to systematically investigate the role of ion shielding on DNA hybridization and compaction. The increased ionic strength corresponds to higher cation concentrations, which effectively shield the negatively charged phosphate groups along the DNA backbone and thus lead to a more stable structure. (45−47) Salt ions weaken the electrostatic repulsion of the phosphates and allow the DNA strands to approach one another, promoting a more compact structure. (48,49)

Figure 3 presents the RI distributions for N > 40 microlasers under different buffer conditions. Figure 3a shows ssDNA-Au NP-functionalized microlasers and provides a baseline for sample-to-sample variations. Upon hybridization with csDNA, a notable upshift in the RI distribution is observed, as shown in Figure 3b for a buffer concentration of 0.01 M. We attribute the increase in RI to the hybridization bringing Au NPs closer to the microlaser surface due to formation of the compact B-form double helix of the DNA. (50)

Figure 3. Detection of DNA compaction at varying ionic strengths of buffer solutions. Histograms of the refractive index of (a) ssDNA-Au NP-functionalized microlasers in a 0.01 M buffer solution (N = 48) and microlasers following hybridization with csDNA in (b) 0.01 M (N = 47) and (c) 0.1 M (N = 49) buffer solutions.

At a higher buffer concentration of 0.1 M, we observed a further increase in RI, with an average change of 0.004 RIU relative to the 0.01 M buffer concentration (p < 0.05). This finding further confirms that an increase in ionic strength increases the compactness of the dsDNA helix, facilitates the closer proximity of the Au NPs to the microlaser surface, and thereby amplifies the RI perceived by the lasing modes.

Having demonstrated that microlasers functionalized with Au NPs provide an effective platform for sensing DNA hybridization and distinguishing different ionic strengths in ensembles of microlasers, we now explore the detection of DNA hybridization of strands with varying lengths. To do so, we follow the RI change in the vicinity of individual microlasers due to hybridization events in real time. Specifically, a microlaser decorated with ssDNA conjugated to a NP at its 5′-terminus is continuously monitored for spectral changes, while csDNA is added in solution (Figure 4a). In Figure 4b, we show a TE/TM pair of WGM modes and follow their shift over the course of the experiment. The corresponding changes in RI, calculated from the spectral shifts, are plotted in Figure 4c. (Additional lasing modes are present in the spectrum but are not displayed for the sake of simplicity.)

Figure 4. Real-time detection of DNA hybridization on the surface of a microlaser. (a) Schematic representation of DNA hybridization on single-stranded DNA (ssDNA) functionalized with Au nanoparticles (Au NPs). (b) Spectral shifts of a selected TM and TE mode from a single microlaser at different time points during the reaction. (c) Transient refractive index change calculated from the microlaser spectra acquired during DNA hybridization on the laser surface. Time zero (t = 0) indicates the moment csDNA was introduced into the solution. Filled diamonds indicate specific time points with corresponding spectra shown in panel b.

Before the addition of csDNA, the spectra and the calculated corresponding RIs remain unchanged, as indicated by the blue and lilac points and spectra in panels c and b, respectively, of Figure 4. Upon introduction of csDNA at time zero, a red-shift in both the TM and TE modes is observed, corresponding to an increase in the RI. Once the system reaches equilibrium, the spectra stabilize, as represented by the green and pink points and spectra in panels c and b, respectively, of Figure 4. As these experiments are not influenced by inherent variability between microlasers (e.g., in size, internal RI, coverage, etc.), they can monitor the binding of molecules in real time and provide drastically improved sensitivity. As such, it is also possible to measure the hybridization of DNA in the absence of Au NPs (Figure S4). To further validate our findings, we also perform measurements on a control sample consisting of carboxylated microlasers without ssDNA attached to the surface. Upon addition of csDNA, no significant increase in the refractive index is observed (Figure S5), confirming that the observed RI shift in our primary experiments is specifically due to DNA hybridization rather than nonspecific interactions.

We also explored different hybridization configurations. The Au NPs were on the ssDNA, csDNA, both, or neither; real-time hybridization curves were obtained, and the changes in refractive index are compared in Figure S6. Notably, the RI change was found to be most pronounced when the Au NPs were attached to the ssDNA, which is the primary focus of this study.

Finally, we developed an inverted microlaser-based test system for DNA sensing, which may also be employed in the future as target-sensitive hairpin-based drug delivery system. (51) To explore this, we employed a six-nucleotide hairpin (HP) sequence construct forming a four-nucleotide loop (51) and modified with Au NPs by amide coupling of COOH-modified Au NPs with amino linker-functionalized hairpin DNA strands on the 5′-end, as detailed in the Methods of the Supporting Information. The baseline RI distribution for microlasers conjugated with a ssDNA (Figure 5a) agrees with the RI values previously seen in samples with ssDNA-NPs (Figure 2g) and hybridized systems containing csDNA (Figure 2h). When adding csDNA, we expected that csDNA replaces the HP, resulting in a decrease in RI by removal of the Au NPs. However, contrary to this expectation, an increase in RI was observed. Binding energy predictions (see Figure S7) and melting temperature measurements (see Figures S8 and S9) indicate that at room temperature (RT), the high binding energies, derived from two sets of three matching base pairs, maintain the stability of the test system. This causes a contraction in the overall construct length, bringing Au NPs closer to the microlaser surface, as observed when the csDNA binds, and consequently increasing the measured RI.

Figure 5. Refractive index change upon addition and substitution of hairpin DNA. (a) Refractive index histogram for microlasers functionalized with ssDNA. (b) Refractive index histogram after addition of the HP33 hairpin. (c–e) Refractive index histograms after substitution was performed by addition of csDNA for a 1 h reaction at (c) room temperature (RT), (d) 37 °C, and (e) 60 °C. Refractive index measurements were performed at RT in all cases.

After performing hybridization at increased temperatures of 37 and 60 °C for 1 h, we observed the anticipated substitution of HP-Au NPs, evidenced by the decrease in the local RI. At 37 °C (Figure 5d), partial removal of HP-Au NPs was observed, with the RI remaining significantly above that of ssDNA-conjugated microlasers. At 60 °C (Figure 5e), nearly complete removal was achieved, and the RI returned to the range observed for unmodified samples (Figure 5a).

In summary, we demonstrated an innovative approach to nucleic acid sensing using WGM microlasers functionalized with DNA and Au NPs. Our method leverages real-time monitoring of RI changes near the microlaser surface, providing a sensitive platform for detecting DNA hybridization and structural dynamics. It enables detection of sequences in two distinct configurations: either by immobilizing the target complementary strand on the laser surface with a Au NP attached to its 5′-end or by binding a bare strand to the laser surface and complementing this with a Au NP-modified hairpin strand. In both scenarios, we successfully detected an unmodified target DNA sequence. Compared to many fluorescence-based methods, our technique requires only minor 5′-end modifications on the DNA, effectively circumventing the issue of fluorophore quenching. (52) The addition of Au NPs significantly enhances the sensitivity of this WGM-based detection as RI changes become more pronounced with nanoparticle proximity. Additionally, we explored the influence of ionic strength on hybridization, showing that variations in ion concentration affect DNA compactness and, consequently, RI shifts. Furthermore, a hairpin-based test system has been developed to assess DNA hybridization as a potential controlled release mechanism, enabling potential applications in targeted drug delivery.

Our findings pave the way for broader applications of WGM microlaser sensors, particularly in areas requiring precise detection of nucleic acid interactions, such as diagnostics and environmental monitoring. This platform enables the use of customizeable DNA sequences tailored to bind various targets, e.g., nucleic acid sequences by base pairing, to small molecules or peptide/proteins using aptamer sequences.

Finally, our platform provides a highly adaptable basis for sequence-specific detection systems. Understanding conformational changes in nucleic acids and investigating biomechanical forces within cells are increasingly important for elucidating cellular functions and molecular interactions. The structural transitions in DNA and RNA─such as folding, hybridization, and denaturation─are critical for processes such as transcription, replication, and signaling. Integration of this system with different capture strands has the potential to enhance multiplexed sensing capabilities, enabling simultaneous monitoring of multiple analytes in complex biological samples, potentially redefining current approaches to nucleic acid detection and analysis.

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The research data underpinning this publication can be accessed at https://doi.org/10.15125/BATH-01497. (53)

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Corresponding Authors
- Soraya Caixeiro - Department of Chemistry and Biochemistry, Humboldt Centre for Nano- and Biophotonics, Institute for Light and Matter, Greinstrasse 4-6, 50939 Cologne, Germany; Centre for Photonics and Photonic Materials, Department of Physics, University of Bath, Bath BA2 7AY, United Kingdom; https://orcid.org/0000-0003-4605-957X; Email: [email protected]
- Stephanie Kath-Schorr - Department of Chemistry and Biochemistry, Institute of Organic Chemistry, Greinstrasse 4, 50939 Cologne, Germany; https://orcid.org/0000-0002-5180-360X; Email: [email protected]
- Malte C. Gather - Department of Chemistry and Biochemistry, Humboldt Centre for Nano- and Biophotonics, Institute for Light and Matter, Greinstrasse 4-6, 50939 Cologne, Germany; Centre of Biophotonics, SUPA School of Physics and Astronomy, University of St Andrews, St Andrews KY16 9SS, United Kingdom; https://orcid.org/0000-0002-4857-5562; Email: [email protected]
Authors
- Robert Dörrenhaus - Department of Chemistry and Biochemistry, Institute of Organic Chemistry, Greinstrasse 4, 50939 Cologne, Germany; https://orcid.org/0009-0006-4685-9939
- Anna Popczyk - Department of Chemistry and Biochemistry, Humboldt Centre for Nano- and Biophotonics, Institute for Light and Matter, Greinstrasse 4-6, 50939 Cologne, Germany
- Marcel Schubert - Department of Chemistry and Biochemistry, Humboldt Centre for Nano- and Biophotonics, Institute for Light and Matter, Greinstrasse 4-6, 50939 Cologne, Germany
Author Contributions
S.C. and R.D. contributed equally to this work.
Funding
This work received financial support from the Humboldt Foundation (Alexander von Humboldt professorship to M.C.G.).
Notes
The authors declare no competing financial interest.
The research data underpinning this publication can be accessed at https://doi.org/10.15125/BATH-01497 (ref 53).

Acknowledgments

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The authors thank Prof. Jan Riemer for fruitful discussions.

References

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A review. The proposal of a double-helical structure for DNA over 60 years ago provided an eminently satisfying explanation for the heritability of genetic information. But why is DNA, and not RNA, now the dominant biol. information store. We argue that in addn. to its coding function, the ability of DNA, unlike RNA, to adopt a B-DNA structure confers advantages both for information accessibility and for packaging. The information encoded by DNA is both digital - the precise base specifying, for example, amino acid sequences - and analog. The latter dets. the sequence-dependent physicochem. properties of DNA, for example, its stiffness and susceptibility to strand sepn. Most importantly, DNA chirality enables the formation of supercoiling under torsional stress. We review recent evidence suggesting that DNA supercoiling, particularly that generated by DNA translocases, is a major driver of gene regulation and patterns of chromosomal gene organization, and in its guise as a promoter of DNA packaging enables DNA to act as an energy store to facilitate the passage of translocating enzymes such as RNA polymerase.
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Schroeder, R.; Barta, A.; Semrad, K. Strategies for RNA folding and assembly. Nat. Rev. Mol. Cell Biol. 2004, 5, 908– 919, DOI: 10.1038/nrm1497
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Strategies for RNA folding and assembly
Schroeder, Renee; Barta, Andrea; Semrad, Katharina
Nature Reviews Molecular Cell Biology (2004), 5 (11), 908-919CODEN: NRMCBP; ISSN:1471-0072. (Nature Publishing Group)
A review. RNA is structurally very flexible, which provides the basis for its functional diversity. An RNA mol. can often adopt different conformations, which enables the regulation of its function through folding. Proteins help RNAs reach their functionally active conformation by increasing their structural stability or by chaperoning the folding process. Large, dynamic RNA-protein complexes, such as the ribosome or the spliceosome, require numerous proteins that coordinate conformational switches of the RNA components during assembly and during their resp. activities.
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Saccà, B.; Niemeyer, C. M. DNA origami: The art of folding DNA. Angew. Chemie - Int. Ed. 2012, 51, 58– 66, DOI: 10.1002/anie.201105846
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DNA Origami: The Art of Folding DNA
Sacca, Barbara; Niemeyer, Christof M.
Angewandte Chemie, International Edition (2012), 51 (1), 58-66CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
A review. The advent of DNA origami technol. greatly simplified the design and construction of nanometer-sized DNA objects. The self-assembly of a DNA-origami structure is a straightforward process in which a long single-stranded scaffold (often from the phage M13mp18) is folded into basically any desired shape with the help of a multitude of short helper strands. This approach enables the ready generation of objects with an addressable surface area of a few thousand nm2 and with a single "pixel" resoln. of about 6 nm. The process is rapid, puts low demands on exptl. conditions, and delivers target products in high yields. These features make DNA origami the method of choice in structural DNA nanotechnol. when two- and three-dimensional objects are desired. This Minireview summarizes recent advances in the design of DNA origami nanostructures, which open the door to numerous exciting applications.
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Fallmann, J. Recent advances in RNA folding. J. Biotechnol. 2017, 261, 97– 104, DOI: 10.1016/j.jbiotec.2017.07.007
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Recent advances in RNA folding
Fallmann, Joerg; Will, Sebastian; Engelhardt, Jan; Gruening, Bjoern; Backofen, Rolf; Stadler, Peter F.
Journal of Biotechnology (2017), 261 (), 97-104CODEN: JBITD4; ISSN:0168-1656. (Elsevier B.V.)
In the realm of nucleic acid structures, secondary structure forms a conceptually important intermediate level of description and explains the dominating part of the free energy of structure formation. Secondary structures are well conserved over evolutionary time-scales and for many classes of RNAs evolve slower than the underlying primary sequences. Given the close link between structure and function, secondary structure is routinely used as a basis to explain exptl. findings. Recent technol. advances, finally, have made it possible to assay secondary structure directly using high throughput methods. From a computational biol. point of view, secondary structures have a special role because they can be computed efficiently using exact dynamic programming algorithms. In this contribution we provide a short overview of RNA folding algorithms, recent addns. and variations and address methods to align, compare, and cluster RNA structures, followed by a tabular summary of the most important software suites in the fields.
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Fakih, H. H.; Itani, M. M.; Karam, P. Gold nanoparticles-coated polystyrene beads for the multiplex detection of viral DNA. Sensors Actuators, B Chem. 2017, 250, 446– 452, DOI: 10.1016/j.snb.2017.04.066
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There is no corresponding record for this reference.
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Qi, Y.; Song, D.; Chen, Y. Colorimetric oligonucleotide-based sensor for ultra-low Hg2+ in contaminated environmental medium: Convenience, sensitivity and mechanism. Sci. Total Environ. 2021, 766, 142579, DOI: 10.1016/j.scitotenv.2020.142579
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Colorimetric oligonucleotide-based sensor for ultra-low Hg2+ in contaminated environmental medium: Convenience, sensitivity and mechanism
Qi, Yingying; Song, Dandan; Chen, Yiting
Science of the Total Environment (2021), 766 (), 142579CODEN: STENDL; ISSN:0048-9697. (Elsevier B.V.)
A colorimetric sensor for detection of Hg2+ is developed via graphene oxide/gold nanoparticles (GO/AuNPs) nanocomposite as peroxidase mimic. In the absence of Hg2+ the adsorption of ss-DNA on GO/AuNPs resulted in the decrease of peroxidase-like activity of GO/AuNPs, which catalyzed the oxidn. of 3, 3, 5, 5-tetramethylbenzidine (TMB) to be very light blue. In the presence of Hg2+ the oligonucleotides of T-Hg2+-T conformation formed by thymine-Hg(II)-thymine interaction could not be adsorbed or bonded on GO/AuNPs, and the GO/AuNPs resumed their original high activity of peroxidase mimic and catalyzed the oxidn. of TMB into distinct blue product. Under optimized conditions, the absorbance value at the wavelength of 655 nm (A655) was linearly related with the concn. of Hg2+ in the range between 5.2 x 10-9 M and 1.2 x 10-7 M with a detection limit of 3.8 x 10-10 M. By visual observation with the naked eye, Hg2+as low as 3.3 x 10-7 M could cause color change in soln. The specific T-Hg2+-T binding made it easy to selectively detect Hg2+. The results show that the colorimetric assay offers great potential for the detection of Hg2+ in real samples.
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García-Mendiola, T. Functionalization of a Few-Layer Antimonene with Oligonucleotides for DNA Sensing. ACS Appl. Nano Mater. 2020, 3, 3625– 3633, DOI: 10.1021/acsanm.0c00335
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Functionalization of a Few-Layer Antimonene with Oligonucleotides for DNA Sensing
Garcia-Mendiola, Tania; Gutierrez-Sanchez, Cristina; Gibaja, Carlos; Torres, Inigo; Buso-Rogero, Carlos; Pariente, Felix; Solera, Jesus; Razavifar, Zahra; Palacios, Juan J.; Zamora, Felix; Lorenzo, Encarnacion
ACS Applied Nano Materials (2020), 3 (4), 3625-3633CODEN: AANMF6; ISSN:2574-0970. (American Chemical Society)
Antimonene, a novel group 15 two-dimensional material, is functionalized with an oligonucleotide as a first step to DNA sensor development. The functionalization process leads to a few-layer antimonene modified with DNA that after deposition on gold screen-printed electrodes gives a simple and efficient DNA electrochem. sensing platform. The authors provide theor. and exptl. data of the DNA-antimonene interaction, confirming that oligonucleotides interact noncovalently but strongly with antimonene. The potential utility of this antimonene-based sensing device is assessed using, as a case of study, a sequence from the BRCA1 gene as the target DNA. The selectivity of the device allows not only recognition of a specific DNA sequence but also detection of a mutation in this gene assocd. with breast cancer, directly in clin. samples.
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Ambartsumyan, O.; Gribanyov, D.; Kukushkin, V.; Kopylov, A.; Zavyalova, E. SERS-based biosensors for virus determination with oligonucleotides as recognition elements. Int. J. Mol. Sci. 2020, 21, 3373, DOI: 10.3390/ijms21093373
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SERS-based biosensors for virus determination with oligonucleotides as recognition elements
Ambartsumyan, Oganes; Gribanyov, Dmitry; Kukushkin, Vladimir; Kopylov, Alexey; Zavyalova, Elena
International Journal of Molecular Sciences (2020), 21 (9), 3373CODEN: IJMCFK; ISSN:1422-0067. (MDPI AG)
A review. Viral infections are among the main causes of morbidity and mortality of humans; sensitive and specific diagnostic methods for the rapid identification of viral pathogens are required. Surface-enhanced Raman spectroscopy (SERS) is one of the most promising techniques for routine anal. due to its excellent sensitivity, simple and low-cost instrumentation and minimal required sample prepn. The outstanding sensitivity of SERS is achieved due to tiny nanostructures which must be assembled before or during the anal. As for specificity, it may be provided using recognition elements. Antibodies, complimentary nucleic acids and aptamers are the most usable recognition elements for virus identification. Here, SERS-based biosensors for virus identification with oligonucleotides as recognition elements are reviewed, and the potential of these biosensors is discussed.
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Zheng, J.; Chen, C.; Wang, X.; Zhang, F.; He, P. A sequence-specific DNA sensor for Hepatitis B virus diagnostics based on the host-guest recognition. Sensors Actuators, B Chem. 2014, 199, 168– 174, DOI: 10.1016/j.snb.2014.03.110
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There is no corresponding record for this reference.
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Paludan, S. R.; Bowie, A. G. Immune Sensing of DNA. Immunity 2013, 38, 870– 880, DOI: 10.1016/j.immuni.2013.05.004
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Immune Sensing of DNA
Paludan, Soeren R.; Bowie, Andrew G.
Immunity (2013), 38 (5), 870-880CODEN: IUNIEH; ISSN:1074-7613. (Elsevier Inc.)
A review. Although it has been appreciated for some years that cytosolic DNA is immune stimulatory, it is only in the past five years that the mol. basis of DNA sensing by the innate immune system has begun to be revealed. In particular it has been described how DNA induces type I interferon, central in antiviral responses and a mediator of autoimmunity. To date more than ten cytosolic receptors of DNA have been proposed, but STING is a key adaptor protein for most DNA-sensing pathways, and we are now beginning to understand the signaling mechanisms for STING. In this review we describe the recent progress in understanding signaling mechanisms activated by DNA and the relevance of DNA sensing to pathogen responses and autoimmunity. We highlight new insights gained into how and why the immune system responds to both pathogen and self DNA and define important questions that now need to be addressed in the field of innate immune activation by DNA.
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Huang, K. J. Signal amplification for electrochemical DNA biosensor based on two-dimensional graphene analogue tungsten sulfide-graphene composites and gold nanoparticles. Sensors Actuators, B Chem. 2014, 191, 828– 836, DOI: 10.1016/j.snb.2013.10.072
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Signal amplification for electrochemical DNA biosensor based on two-dimensional graphene analogue tungsten sulfide-graphene composites and gold nanoparticles
Huang, Ke-Jing; Liu, Yu-Jie; Wang, Hai-Bo; Gan, Tian; Liu, Yan-Ming; Wang, Ling-Ling
Sensors and Actuators, B: Chemical (2014), 191 (), 828-836CODEN: SABCEB; ISSN:0925-4005. (Elsevier B.V.)
A novel two-dimensional graphene analog tungsten sulfide-graphene (WS2-Gr) composite was synthesized to achieve excellent electrochem. properties for applications as DNA biosensor. Gr served as a 2D conductive skeleton that supported a highly electrolytic accessible surface area of WS2 nanocomposite which was prepd. by a hydrothermal method. A sensitive electrochem. DNA biosensor was fabricated by using the WS2-Gr-chitosan composites modified glassy carbon electrode to anchor Au nanoparticles (AuNPs), which subsequently used to capture ssDNA sequences. Cyclic voltammetry and electrochem. impedance spectroscopy were carried out for the characterization of modified electrodes. Under optimum conditions, the developed biosensor showed a good linear relationship between the current value and logarithm of the target DNA concn. ranging from 0.01 to 500 pM with a detection limit of 0.0023 pM. The DNA biosensor exhibited excellent discrimination ability to detect one-base mismatched DNA, three-base mismatched DNA and non-complementary DNA sequence. This work described a simple strategy for the prepn. of a stable and conductive interface for electrochem. detection of DNA hybridization and opened a path for the application of WS2-Gr nanocomposite in DNA electrochem. biosensing anal.
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Toropov, N. Review of biosensing with whispering-gallery mode lasers. Light: Sci. Appl. 2021, 10, 42, DOI: 10.1038/s41377-021-00471-3
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Review of biosensing with whispering-gallery mode lasers
Toropov, Nikita; Cabello, Gema; Serrano, Mariana P.; Gutha, Rithvik R.; Rafti, Matias; Vollmer, Frank
Light: Science & Applications (2021), 10 (1), 42CODEN: LSAIAZ; ISSN:2047-7538. (Nature Research)
Abstr.: Lasers are the pillars of modern optics and sensing. Microlasers based on whispering-gallery modes (WGMs) are miniature in size and have excellent lasing characteristics suitable for biosensing. WGM lasers have been used for label-free detection of single virus particles, detection of mol. electrostatic changes at biointerfaces, and barcode-type live-cell tagging and tracking. The most recent advances in biosensing with WGM microlasers are described in this review. We cover the basic concepts of WGM resonators, the integration of gain media into various active WGM sensors and devices, and the cutting-edge advances in photonic devices for micro- and nanoprobing of biol. samples that can be integrated with WGM lasers.
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Fan, X.; Yun, S.-H. The potential of optofluidic biolasers. Nat. Methods 2014, 11, 141– 7, DOI: 10.1038/nmeth.2805
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The potential of optofluidic biolasers
Fan, Xudong; Yun, Seok-Hyun
Nature Methods (2014), 11 (2), 141-147CODEN: NMAEA3; ISSN:1548-7091. (Nature Publishing Group)
A review. Optofluidic biolasers are emerging as a highly sensitive way to measure changes in biol. mols. Biolasers, which incorporate biol. material into the gain medium and contain an optical cavity in a fluidic environment, can use the amplification that occurs during laser generation to quantify tiny changes in biol. processes in the gain medium. We describe the principle of the optofluidic biolaser, review recent progress and provide our outlooks on potential applications and directions for developing this technol.
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Pan, T.; Lu, D.; Xin, H.; Li, B. Biophotonic probes for bio-detection and imaging. Light: Sci. Appl. 2021, 10, 124, DOI: 10.1038/s41377-021-00561-2
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Biophotonic probes for bio-detection and imaging
Pan, Ting; Lu, Dengyun; Xin, Hongbao; Li, Baojun
Light: Science & Applications (2021), 10 (1), 124CODEN: LSAIAZ; ISSN:2047-7538. (Nature Research)
A review. The rapid development of biophotonics and biomedical sciences makes a high demand on photonic structures to be interfaced with biol. systems that are capable of manipulating light at small scales for sensitive detection of biol. signals and precise imaging of cellular structures. However, conventional photonic structures based on artificial materials (either inorg. or toxic org.) inevitably show incompatibility and invasiveness when interfacing with biol. systems. The design of biophotonic probes from the abundant natural materials, particularly biol. entities such as virus, cells and tissues, with the capability of multifunctional light manipulation at target sites greatly increases the biocompatibility and minimizes the invasiveness to biol. microenvironment. In this review, advances in biophotonic probes for bio-detection and imaging are reviewed. We emphatically and systematically describe biol. entities-based photonic probes that offer appropriate optical properties, biocompatibility, and biodegradability with different optical functions from light generation, to light transportation and light modulation. Three representative biophotonic probes, i.e., biol. lasers, cell-based biophotonic waveguides and bio-microlenses, are reviewed with applications for bio-detection and imaging. Finally, perspectives on future opportunities and potential improvements of biophotonic probes are also provided.
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Caixeiro, S. Local Sensing of Absolute Refractive Index During Protein-Binding using Microlasers with Spectral Encoding. Adv. Opt. Mater. 2023, 11, 2300530, DOI: 10.1002/adom.202300530
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There is no corresponding record for this reference.
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Schubert, M. Monitoring contractility in cardiac tissue with cellular resolution using biointegrated microlasers. Nat. Photonics 2020, 14, 452– 458, DOI: 10.1038/s41566-020-0631-z
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Monitoring contractility in cardiac tissue with cellular resolution using biointegrated microlasers
Schubert, Marcel; Woolfson, Lewis; Barnard, Isla R. M.; Dorward, Amy M.; Casement, Becky; Morton, Andrew; Robertson, Gavin B.; Appleton, Paul L.; Miles, Gareth B.; Tucker, Carl S.; Pitt, Samantha J.; Gather, Malte C.
Nature Photonics (2020), 14 (7), 452-458CODEN: NPAHBY; ISSN:1749-4885. (Nature Research)
Abstr.: The contractility of cardiac cells is a key parameter that describes the biomech. characteristics of the beating heart, but functional monitoring of three-dimensional cardiac tissue with single-cell resoln. remains a major challenge. Here, we introduce microscopic whispering-gallery-mode lasers into cardiac cells to realize all-optical recording of transient cardiac contraction profiles with cellular resoln. The brilliant emission and high spectral sensitivity of microlasers to local changes in refractive index enable long-term tracking of individual cardiac cells, monitoring of drug administration, accurate measurements of organ-scale contractility in live zebrafish, and robust contractility sensing through hundreds of micrometres of rat heart tissue. Our study reveals changes in sarcomeric protein d. as an underlying factor to cardiac contraction. More broadly, the use of novel micro- and nanoscopic lasers as non-invasive, biointegrated optical sensors brings new opportunities to monitor a wide range of physiol. parameters with cellular resoln.
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Caixeiro, S.; Gaio, M.; Marelli, B.; Omenetto, F. G.; Sapienza, R. Silk-Based Biocompatible Random Lasing. Adv. Opt. Mater. 2016, 4, 998– 1003, DOI: 10.1002/adom.201600185
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Silk-Based Biocompatible Random Lasing
Caixeiro, Soraya; Gaio, Michele; Marelli, Benedetto; Omenetto, Fiorenzo G.; Sapienza, Riccardo
Advanced Optical Materials (2016), 4 (7), 998-1003CODEN: AOMDAX; ISSN:2195-1071. (Wiley-VCH Verlag GmbH & Co. KGaA)
Here, a biocompatible random laser made entirely of doped silk, functional in aq. media, showing clear threshold behavior and spectral narrowing are demonstrated. Furthermore, the device is capable of probing changes in a chem. environment, namely, pH, due to the intrinsic nonlinear response and the large spectral purity.
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Wang, Y. Demonstration of intracellular real-time molecular quantification via FRET-enhanced optical microcavity. Nat. Commun. 2022, 13, 6685, DOI: 10.1038/s41467-022-34547-4
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There is no corresponding record for this reference.
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Duan, R.; Hao, X.; Li, Y.; Li, H. Detection of acetylcholinesterase and its inhibitors by liquid crystal biosensor based on whispering gallery mode. Sensors Actuators, B Chem. 2020, 308, 127672, DOI: 10.1016/j.snb.2020.127672
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There is no corresponding record for this reference.
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Schubert, M. Lasing within Live Cells Containing Intracellular Optical Microresonators for Barcode-Type Cell Tagging and Tracking. Nano Lett. 2015, 15, 5647– 5652, DOI: 10.1021/acs.nanolett.5b02491
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Lasing within Live Cells Containing Intracellular Optical Microresonators for Barcode-Type Cell Tagging and Tracking
Schubert, Marcel; Steude, Anja; Liehm, Philipp; Kronenberg, Nils M.; Karl, Markus; Campbell, Elaine C.; Powis, Simon J.; Gather, Malte C.
Nano Letters (2015), 15 (8), 5647-5652CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)
The authors report on a laser that is fully embedded within a single live cell. By harnessing natural endocytosis of the cell, the authors introduce a fluorescent whispering gallery mode (WGM) microresonator into the cell cytoplasm. On pumping with nanojoule light pulses, green laser emission was generated inside the cells. The authors' approach can be applied to different cell types, and cells with microresonators remain viable for weeks under std. conditions. The characteristics of the lasing spectrum provide each cell with a barcode-type label which enables uniquely identifying and tracking individual migrating cells. Self-sustained lasing from cells paves the way to new forms of cell tracking, intracellular sensing, and adaptive imaging.
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Martino, N. Wavelength-encoded laser particles for massively multiplexed cell tagging. Nat. Photonics 2019, 13, 720– 727, DOI: 10.1038/s41566-019-0489-0
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Wavelength-encoded laser particles for massively multiplexed cell tagging
Martino, Nicola; Kwok, Sheldon J. J.; Liapis, Andreas C.; Forward, Sarah; Jang, Hoon; Kim, Hwi-Min; Wu, Sarah J.; Wu, Jiamin; Dannenberg, Paul H.; Jang, Sun-Joo; Lee, Yong-Hee; Yun, Seok-Hyun
Nature Photonics (2019), 13 (10), 720-727CODEN: NPAHBY; ISSN:1749-4885. (Nature Research)
Large-scale single-cell analyses have become increasingly important given the role of cellular heterogeneity in complex biol. systems. However, no techniques at present enable optical imaging of uniquely tagged individual cells. Fluorescence-based approaches can distinguish only a small no. of distinct cells or cell groups at a time because of spectral crosstalk between conventional fluorophores. Here we investigate large-scale cell tracking using intracellular laser particles as imaging probes that emit coherent laser light with a characteristic wavelength. Made of silica-coated semiconductor microcavities, these laser particles have single-mode emission over a broad range from 1,170 nm to 1,580 nm with sub-nanometer linewidths, enabling massive spectral multiplexing. We explore the stability and biocompatibility of these probes in vitro and their utility for wavelength-multiplexed cell tagging and imaging. We demonstrate real-time tracking of thousands of individual cells in a three-dimensional tumor model over several days, showing different behavioral phenotypes.
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Fikouras, A. H. Non-obstructive intracellular nanolasers. Nat. Commun. 2018, 9, 4817, DOI: 10.1038/s41467-018-07248-0
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Non-obstructive intracellular nanolasers
Fikouras Alasdair H; Schubert Marcel; Karl Markus; Kumar Jothi D; Di Falco Andrea; Gather Malte C; Powis Simon J
Nature communications (2018), 9 (1), 4817 ISSN:.
Molecular dyes, plasmonic nanoparticles and colloidal quantum dots are widely used in biomedical optics. Their operation is usually governed by spontaneous processes, which results in broad spectral features and limited signal-to-noise ratio, thus restricting opportunities for spectral multiplexing and sensing. Lasers provide the ultimate spectral definition and background suppression, and their integration with cells has recently been demonstrated. However, laser size and threshold remain problematic. Here, we report on the design, high-throughput fabrication and intracellular integration of semiconductor nanodisk lasers. By exploiting the large optical gain and high refractive index of GaInP/AlGaInP quantum wells, we obtain lasers with volumes 1000-fold smaller than the eukaryotic nucleus (Vlaser < 0.1 μm(3)), lasing thresholds 500-fold below the pulse energies typically used in two-photon microscopy (Eth ≈ 0.13 pJ), and excellent spectral stability (<50 pm wavelength shift). Multiplexed labeling with these lasers allows cell-tracking through micro-pores, thus providing a powerful tool to study cell migration and cancer invasion.
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Dalaka, E. Deformable microlaser force sensing. Light: Sci. Appl. 2024, 13, 129, DOI: 10.1038/s41377-024-01471-9
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There is no corresponding record for this reference.
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Pirnat, G.; Marinčič, M.; Ravnik, M.; Humar, M. Quantifying local stiffness and forces in soft biological tissues using droplet optical microcavities. Proc. Natl. Acad. Sci. U. S. A. 2024, 121 (4), e2314884121 DOI: 10.1073/pnas.2314884121
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There is no corresponding record for this reference.
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Leonetti, M. Optical gain in DNA-DCM for lasing in photonic materials. Opt. Lett. 2009, 34, 3764– 3766, DOI: 10.1364/OL.34.003764
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Optical gain in DNA-DCM for lasing in photonic materials
Leonetti, Marco; Sapienza, Riccardo; Ibisate, Marta; Conti, Claudio; Lopez, Cefe
Optics Letters (2009), 34 (24), 3764-3766CODEN: OPLEDP; ISSN:0146-9592. (Optical Society of America)
We present a detailed study of the gain length in an active medium obtained by doping of DNA strands with 4-(dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran dye mols. The superior thermal stability of the composite and its low quenching permit one to obtain an optical gain coeff. larger than 300 cm-1. We also demonstrate that such an active material is feasible for the infiltration into photonic nanostructures, allowing one to obtain fluorescent photonic crystals and promising lasing properties.
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Lee, W.; Chen, Q.; Fan, X.; Yoon, D. K. Digital DNA detection based on a compact optofluidic laser with ultra-low sample consumption. Lab Chip 2016, 16, 4770– 4776, DOI: 10.1039/C6LC01258B
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Digital DNA detection based on a compact optofluidic laser with ultra-low sample consumption
Lee, Wonsuk; Chen, Qiushu; Fan, Xudong; Yoon, Dong Ki
Lab on a Chip (2016), 16 (24), 4770-4776CODEN: LCAHAM; ISSN:1473-0189. (Royal Society of Chemistry)
DNA lasers self-amplify optical signals from a DNA analyte as well as thermodn. differences between sequences, allowing quasi-digital DNA detection. However, these systems have drawbacks, such as relatively large sample consumption and complicated dye labeling. Moreover, although the lasing signal can detect the target DNA, it is superimposed on an unintended fluorescence background, which persists for non-target DNA samples as well. From an optical point of view, it is thus not truly digital detection and requires spectral anal. to identify the target. In this work, we propose and demonstrate an optofluidic laser that has a single layer of DNA mols. as the gain material. A target DNA produces intensive laser emission comparable to existing DNA lasers, while any unnecessary fluorescence background is successfully suppressed. As a result, the target DNA can be detected with a single laser pulse, in a truly digital manner. Since the DNA mols. cover only a single layer on the surface of the laser microcavity, the DNA sample consumption is a few orders of magnitude lower than that of existing DNA lasers. Furthermore, the DNA mols. are stained by simply immersing the microcavity in the intercalating dye soln., and thus the proposed DNA laser is free of any complex dye-labeling process prior to anal.
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Tanwar, S.; Kaur, V.; Kaur, G.; Sen, T. Broadband SERS Enhancement by DNA Origami Assembled Bimetallic Nanoantennas with Label-Free Single Protein Sensing. J. Phys. Chem. Lett. 2021, 12, 8141– 8150, DOI: 10.1021/acs.jpclett.1c02272
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Broadband SERS Enhancement by DNA Origami Assembled Bimetallic Nanoantennas with Label-Free Single Protein Sensing
Tanwar, Swati; Kaur, Vishaldeep; Kaur, Gagandeep; Sen, Tapasi
Journal of Physical Chemistry Letters (2021), 12 (33), 8141-8150CODEN: JPCLCD; ISSN:1948-7185. (American Chemical Society)
Engineering hotspots in surface-enhanced Raman spectroscopy (SERS) through precisely controlled assembly of plasmonic nanostructures capable of expanding intense field enhancement are highly desirable to enhance the potentiality of SERS as a label-free optical tool for single mol. detection. Inspired by DNA origami technique, we constructed plasmonic dimer nanoantennas with a tunable gap decorated with Ag-coated Au nanostars on origami. Herein, we demonstrate the single-mol. SERS enhancements of three dyes with emission in different spectral regions after incorporation of single dye mols. in between two nanostars. The enhancement factors (EFs) achieved in the range of 109-1010 for all the single dye mols., under both resonant and nonresonant excitation conditions, would enable enhanced photostability during time-series measurement. We further successfully explored the potential of our designed nanoantennas to accommodate and detect a single thrombin protein mol. after selective placement in the wide nanogap of 10 nm. Our results suggest that such nanoantennas can serve as a broadband SERS enhancer and enable specific detection of target biol. mols. with single-mol. sensitivity.
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Das, M.; Shim, K. H.; An, S. S. A.; Yi, D. K. Review on gold nanoparticles and their applications. Toxicol. Environ. Health Sci. 2011, 3, 193– 205, DOI: 10.1007/s13530-011-0109-y
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Dreaden, E. C.; Alkilany, A. M.; Huang, X.; Murphy, C. J.; El-Sayed, M. A. The golden age: Gold nanoparticles for biomedicine. Chem. Soc. Rev. 2012, 41, 2740– 2779, DOI: 10.1039/C1CS15237H
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The golden age: gold nanoparticles for biomedicine
Dreaden, Erik C.; Alkilany, Alaaldin M.; Huang, Xiaohua; Murphy, Catherine J.; El-Sayed, Mostafa A.
Chemical Society Reviews (2012), 41 (7), 2740-2779CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)
A review. Gold nanoparticles have been used in biomedical applications since their first colloidal syntheses more than three centuries ago. However, over the past two decades, their beautiful colors and unique electronic properties have also attracted tremendous attention due to their historical applications in art and ancient medicine and current applications in enhanced optoelectronics and photovoltaics. In spite of their modest alchem. beginnings, gold nanoparticles exhibit phys. properties that are truly different from both small mols. and bulk materials, as well as from other nanoscale particles. Their unique combination of properties is just beginning to be fully realized in range of medical diagnostic and therapeutic applications. This crit. review will provide insights into the design, synthesis, functionalization, and applications of these artificial mols. in biomedicine and discuss their tailored interactions with biol. systems to achieve improved patient health. Further, we provide a survey of the rapidly expanding body of literature on this topic and argue that gold nanotechnol.-enabled biomedicine is not simply an act of gilding the (nanomedicinal) lily', but that a new Golden Age' of biomedical nanotechnol. is truly upon us. Moving forward, the most challenging nanoscience ahead of us will be to find new chem. and phys. methods of functionalizing gold nanoparticles with compds. that can promote efficient binding, clearance, and biocompatibility and to assess their safety to other biol. systems and their long-term term effects on human health and reprodn. (472 refs.).
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Hao, Y.; Fang, L.; Deng, Z. Solvo-driven dimeric nanoplasmon coupling under DNA direction. CCS Chem. 2021, 3, 1359– 1367, DOI: 10.31635/ccschem.020.202000290
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Solvo-driven dimeric nanoplasmon coupling under DNA direction
Hao, Yan; Fang, Lingling; Deng, Zhaoxiang
CCS Chemistry (2021), 3 (4), 1359-1367CODEN: CCCHB2 ISSN:. (Chinese Chemical Society)
Strong coupling is a prerequisite for nanoassemblies to deliver functions and applications unrealizable by noninteracting building units. DNA-Directed metamaterials, albeit highly programmable, often show negligible interunit coupling and accordingly limited functions. Herein a simple but highly effective solvent-driven process for dimeric plasmon coupling under DNA's guidance is reported. The DNA is responsible for a proximity control of plasmonic units to undergo electromagnetic hybridization. This process is inspired by a spontaneous formation of nanoparticle chains in less polar water-miscible solvents. The resulting 1.25 nm surface sepn. is insensitive to DNA linker length as well as solvent/water ratios above a certain threshold, consistent with a Van der Waals colloidal bonding model. Our strategy avoids surface contamination to the nanoassemblies with the DNA linker in position to ensure coupling selectivity and reversibility. The cooperative but orthogonal roles played by DNA and the org. solvents promise bottom-up materials and devices with prescribed functions.
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Proceedings of the National Academy of Sciences of the United States of America (2017), 114 (3), 457-461CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)
Three-dimensional plasmonic superlattice microcavities, made from programmable atom equiv. comprising Au nanoparticles functionalized with DNA, are used as a testbed to study directional light emission. DNA-guided nanoparticle colloidal crystn. allows for the formation of micrometer-scale single-crystal bcc. Au nanoparticle superlattices, with dye mols. coupled to the DNA strands that link the particles together, as a rhombic dodecahedron. Encapsulation in SiO2 allows 1 to create robust architectures with the plasmonically active particles and dye mols. fixed in space. At the micrometer scale, the anisotropic rhombic dodecahedron crystal habit couples with photonic modes to give directional light emission. At the nanoscale, the interaction between the dye dipoles and surface plasmons can be finely tuned by coupling the dye mols. to specific sites of the DNA particle-linker strands, thereby modulating dye-nanoparticle distance (3 different positions are studied). The ability to control dye position with subnanometer precision allows 1 to systematically tune plasmon-excition interaction strength and decay lifetime, the results of which were supported by electrodynamics calcns. that span length scales from nanometers to micrometers. The unique ability to control surface plasmon/exciton interactions within such superlattice microcavities will catalyze studies involving quantum optics, plasmon laser physics, strong coupling, and nonlinear phenomena.
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MicroRNAs are small regulatory RNAs with many biol. functions and disease assocns. The authors showed that in situ hybridization (ISH) using conventional formaldehyde fixation results in substantial microRNA loss from mouse tissue sections, which can be prevented by fixation with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide that irreversibly immobilizes the microRNA at its 5' phosphate. The authors detd. optimal hybridization parameters for 130 locked nucleic acid probes by recording nucleic acid melting temp. during ISH.
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We present a comprehensive overview of sensor technol. exploiting optical whispering gallery mode (WGM) resonances. After a short introduction we begin by detailing the fundamental principles and theory of WGMs in optical microcavities and the transduction mechanisms frequently employed for sensing purposes. Key recent theor. contributions to the modeling and anal. of WGM systems are highlighted. Subsequently we review the state of the art of WGM sensors by outlining efforts made to date to improve current detection limits. Proposals in this vein are numerous and range, for example, from plasmonic enhancements and active cavities to hybrid optomech. sensors, which are already working in the shot noise limited regime. In parallel to furthering WGM sensitivity, efforts to improve the time resoln. are beginning to emerge. We therefore summarize the techniques being pursued in this vein. Ultimately WGM sensors aim for real-world applications, such as measurements of force and temp., or alternatively gas and biosensing. Each such application is thus reviewed in turn, and important achievements are discussed. Finally, we adopt a more forward-looking perspective and discuss the outlook of WGM sensors within both a phys. and biol. context and consider how they may yet push the detection envelope further.
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Evgeniia O. Soloveva, Natalia N. Shevchenko, Nikita S. Kirilkin, Albert A. Rogachev, Mariia S. Kovova, Alexander S. Timin, Vladislava A. Rusakova, Sergei A. Shipilovskikh, Anton A. Starovoytov, Daler R. Dadadzhanov, Nikita Toropov. Inherent luminescence in undoped polystyrene microbeads supporting whispering-gallery modes. Optical Materials 2025, 165 , 117058. https://doi.org/10.1016/j.optmat.2025.117058

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Abstract
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Figure 1
Figure 1. Preparation and optical characterization of the surface coating with gold nanoparticle (Au NP)-functionalized DNA on microlasers. (a) Schematic of the nanoparticle ssDNA conjugation to a carboxyl-functionalized microlaser. (b) Electron microscopy image of a carboxyl-functionalized microlaser. The scale bar is 2 μm. (c) Electron microscopy image of a microlaser decorated with DNA functionalized with 40 nm diameter Au NPs. Scale bars are 2 μm and 500 nm (inset). (e) Green fluorescence from a microlaser functionalized with ssDNA with Cy5 dye. (f) Red fluorescence of same microlaser. (g) Overlay of green and red emission. (h–j) Microlaser with dye-free ssDNA on the surface showing no red fluorescence (h). The hybridization with csDNA containing Cy5 illustrated in panel i leads to the appearance of a red ring in the fluorescence image (j). Scale bars for panels e–h and j are 20 μm.
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Figure 2
Figure 2. Refractive index sensing of DNA surface modifications. (a) Representative lasing spectra from a microlaser in a buffered solution, along with the fitted refractive index. (b) Simulated lasing spectra for microlasers embedded in media of two different refractive indices: n = 1.340 (orange), and n = 1.345 (blue). (c) Close-up of the simulated spectra, highlighting the spectral shifts across different refractive indices and polarization, for azimuthal mode number m = 105. Histograms of external refractive indices calculated from measured laser spectra, with a corresponding box plot, showing (d) carboxyl-functionalized microlasers (N = 71), (e) microlasers conjugated with ssDNA (N = 99), (f) microlasers conjugated with dsDNA (N = 90), (g) microlasers conjugated with ssDNA and Au NPs (N = 65), and (h) microlasers conjugated with dsDNA and Au NPs (N = 91). The illustrations to the right of each histogram depict the configuration for each case.
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Figure 3
Figure 3. Detection of DNA compaction at varying ionic strengths of buffer solutions. Histograms of the refractive index of (a) ssDNA-Au NP-functionalized microlasers in a 0.01 M buffer solution (N = 48) and microlasers following hybridization with csDNA in (b) 0.01 M (N = 47) and (c) 0.1 M (N = 49) buffer solutions.
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Figure 4
Figure 4. Real-time detection of DNA hybridization on the surface of a microlaser. (a) Schematic representation of DNA hybridization on single-stranded DNA (ssDNA) functionalized with Au nanoparticles (Au NPs). (b) Spectral shifts of a selected TM and TE mode from a single microlaser at different time points during the reaction. (c) Transient refractive index change calculated from the microlaser spectra acquired during DNA hybridization on the laser surface. Time zero (t = 0) indicates the moment csDNA was introduced into the solution. Filled diamonds indicate specific time points with corresponding spectra shown in panel b.
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Figure 5
Figure 5. Refractive index change upon addition and substitution of hairpin DNA. (a) Refractive index histogram for microlasers functionalized with ssDNA. (b) Refractive index histogram after addition of the HP33 hairpin. (c–e) Refractive index histograms after substitution was performed by addition of csDNA for a 1 h reaction at (c) room temperature (RT), (d) 37 °C, and (e) 60 °C. Refractive index measurements were performed at RT in all cases.
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  Colorimetric oligonucleotide-based sensor for ultra-low Hg2+ in contaminated environmental medium: Convenience, sensitivity and mechanism
  Qi, Yingying; Song, Dandan; Chen, Yiting
  Science of the Total Environment (2021), 766 (), 142579CODEN: STENDL; ISSN:0048-9697. (Elsevier B.V.)
  A colorimetric sensor for detection of Hg2+ is developed via graphene oxide/gold nanoparticles (GO/AuNPs) nanocomposite as peroxidase mimic. In the absence of Hg2+ the adsorption of ss-DNA on GO/AuNPs resulted in the decrease of peroxidase-like activity of GO/AuNPs, which catalyzed the oxidn. of 3, 3, 5, 5-tetramethylbenzidine (TMB) to be very light blue. In the presence of Hg2+ the oligonucleotides of T-Hg2+-T conformation formed by thymine-Hg(II)-thymine interaction could not be adsorbed or bonded on GO/AuNPs, and the GO/AuNPs resumed their original high activity of peroxidase mimic and catalyzed the oxidn. of TMB into distinct blue product. Under optimized conditions, the absorbance value at the wavelength of 655 nm (A655) was linearly related with the concn. of Hg2+ in the range between 5.2 x 10-9 M and 1.2 x 10-7 M with a detection limit of 3.8 x 10-10 M. By visual observation with the naked eye, Hg2+as low as 3.3 x 10-7 M could cause color change in soln. The specific T-Hg2+-T binding made it easy to selectively detect Hg2+. The results show that the colorimetric assay offers great potential for the detection of Hg2+ in real samples.
10. 10
  García-Mendiola, T. Functionalization of a Few-Layer Antimonene with Oligonucleotides for DNA Sensing. ACS Appl. Nano Mater. 2020, 3, 3625– 3633, DOI: 10.1021/acsanm.0c00335
  10
  Functionalization of a Few-Layer Antimonene with Oligonucleotides for DNA Sensing
  Garcia-Mendiola, Tania; Gutierrez-Sanchez, Cristina; Gibaja, Carlos; Torres, Inigo; Buso-Rogero, Carlos; Pariente, Felix; Solera, Jesus; Razavifar, Zahra; Palacios, Juan J.; Zamora, Felix; Lorenzo, Encarnacion
  ACS Applied Nano Materials (2020), 3 (4), 3625-3633CODEN: AANMF6; ISSN:2574-0970. (American Chemical Society)
  Antimonene, a novel group 15 two-dimensional material, is functionalized with an oligonucleotide as a first step to DNA sensor development. The functionalization process leads to a few-layer antimonene modified with DNA that after deposition on gold screen-printed electrodes gives a simple and efficient DNA electrochem. sensing platform. The authors provide theor. and exptl. data of the DNA-antimonene interaction, confirming that oligonucleotides interact noncovalently but strongly with antimonene. The potential utility of this antimonene-based sensing device is assessed using, as a case of study, a sequence from the BRCA1 gene as the target DNA. The selectivity of the device allows not only recognition of a specific DNA sequence but also detection of a mutation in this gene assocd. with breast cancer, directly in clin. samples.
11. 11
  Ambartsumyan, O.; Gribanyov, D.; Kukushkin, V.; Kopylov, A.; Zavyalova, E. SERS-based biosensors for virus determination with oligonucleotides as recognition elements. Int. J. Mol. Sci. 2020, 21, 3373, DOI: 10.3390/ijms21093373
  11
  SERS-based biosensors for virus determination with oligonucleotides as recognition elements
  Ambartsumyan, Oganes; Gribanyov, Dmitry; Kukushkin, Vladimir; Kopylov, Alexey; Zavyalova, Elena
  International Journal of Molecular Sciences (2020), 21 (9), 3373CODEN: IJMCFK; ISSN:1422-0067. (MDPI AG)
  A review. Viral infections are among the main causes of morbidity and mortality of humans; sensitive and specific diagnostic methods for the rapid identification of viral pathogens are required. Surface-enhanced Raman spectroscopy (SERS) is one of the most promising techniques for routine anal. due to its excellent sensitivity, simple and low-cost instrumentation and minimal required sample prepn. The outstanding sensitivity of SERS is achieved due to tiny nanostructures which must be assembled before or during the anal. As for specificity, it may be provided using recognition elements. Antibodies, complimentary nucleic acids and aptamers are the most usable recognition elements for virus identification. Here, SERS-based biosensors for virus identification with oligonucleotides as recognition elements are reviewed, and the potential of these biosensors is discussed.
12. 12
  Zheng, J.; Chen, C.; Wang, X.; Zhang, F.; He, P. A sequence-specific DNA sensor for Hepatitis B virus diagnostics based on the host-guest recognition. Sensors Actuators, B Chem. 2014, 199, 168– 174, DOI: 10.1016/j.snb.2014.03.110
  There is no corresponding record for this reference.
13. 13
  Paludan, S. R.; Bowie, A. G. Immune Sensing of DNA. Immunity 2013, 38, 870– 880, DOI: 10.1016/j.immuni.2013.05.004
  13
  Immune Sensing of DNA
  Paludan, Soeren R.; Bowie, Andrew G.
  Immunity (2013), 38 (5), 870-880CODEN: IUNIEH; ISSN:1074-7613. (Elsevier Inc.)
  A review. Although it has been appreciated for some years that cytosolic DNA is immune stimulatory, it is only in the past five years that the mol. basis of DNA sensing by the innate immune system has begun to be revealed. In particular it has been described how DNA induces type I interferon, central in antiviral responses and a mediator of autoimmunity. To date more than ten cytosolic receptors of DNA have been proposed, but STING is a key adaptor protein for most DNA-sensing pathways, and we are now beginning to understand the signaling mechanisms for STING. In this review we describe the recent progress in understanding signaling mechanisms activated by DNA and the relevance of DNA sensing to pathogen responses and autoimmunity. We highlight new insights gained into how and why the immune system responds to both pathogen and self DNA and define important questions that now need to be addressed in the field of innate immune activation by DNA.
14. 14
  Huang, K. J. Signal amplification for electrochemical DNA biosensor based on two-dimensional graphene analogue tungsten sulfide-graphene composites and gold nanoparticles. Sensors Actuators, B Chem. 2014, 191, 828– 836, DOI: 10.1016/j.snb.2013.10.072
  14
  Signal amplification for electrochemical DNA biosensor based on two-dimensional graphene analogue tungsten sulfide-graphene composites and gold nanoparticles
  Huang, Ke-Jing; Liu, Yu-Jie; Wang, Hai-Bo; Gan, Tian; Liu, Yan-Ming; Wang, Ling-Ling
  Sensors and Actuators, B: Chemical (2014), 191 (), 828-836CODEN: SABCEB; ISSN:0925-4005. (Elsevier B.V.)
  A novel two-dimensional graphene analog tungsten sulfide-graphene (WS2-Gr) composite was synthesized to achieve excellent electrochem. properties for applications as DNA biosensor. Gr served as a 2D conductive skeleton that supported a highly electrolytic accessible surface area of WS2 nanocomposite which was prepd. by a hydrothermal method. A sensitive electrochem. DNA biosensor was fabricated by using the WS2-Gr-chitosan composites modified glassy carbon electrode to anchor Au nanoparticles (AuNPs), which subsequently used to capture ssDNA sequences. Cyclic voltammetry and electrochem. impedance spectroscopy were carried out for the characterization of modified electrodes. Under optimum conditions, the developed biosensor showed a good linear relationship between the current value and logarithm of the target DNA concn. ranging from 0.01 to 500 pM with a detection limit of 0.0023 pM. The DNA biosensor exhibited excellent discrimination ability to detect one-base mismatched DNA, three-base mismatched DNA and non-complementary DNA sequence. This work described a simple strategy for the prepn. of a stable and conductive interface for electrochem. detection of DNA hybridization and opened a path for the application of WS2-Gr nanocomposite in DNA electrochem. biosensing anal.
15. 15
  Toropov, N. Review of biosensing with whispering-gallery mode lasers. Light: Sci. Appl. 2021, 10, 42, DOI: 10.1038/s41377-021-00471-3
  15
  Review of biosensing with whispering-gallery mode lasers
  Toropov, Nikita; Cabello, Gema; Serrano, Mariana P.; Gutha, Rithvik R.; Rafti, Matias; Vollmer, Frank
  Light: Science & Applications (2021), 10 (1), 42CODEN: LSAIAZ; ISSN:2047-7538. (Nature Research)
  Abstr.: Lasers are the pillars of modern optics and sensing. Microlasers based on whispering-gallery modes (WGMs) are miniature in size and have excellent lasing characteristics suitable for biosensing. WGM lasers have been used for label-free detection of single virus particles, detection of mol. electrostatic changes at biointerfaces, and barcode-type live-cell tagging and tracking. The most recent advances in biosensing with WGM microlasers are described in this review. We cover the basic concepts of WGM resonators, the integration of gain media into various active WGM sensors and devices, and the cutting-edge advances in photonic devices for micro- and nanoprobing of biol. samples that can be integrated with WGM lasers.
16. 16
  Fan, X.; Yun, S.-H. The potential of optofluidic biolasers. Nat. Methods 2014, 11, 141– 7, DOI: 10.1038/nmeth.2805
  16
  The potential of optofluidic biolasers
  Fan, Xudong; Yun, Seok-Hyun
  Nature Methods (2014), 11 (2), 141-147CODEN: NMAEA3; ISSN:1548-7091. (Nature Publishing Group)
  A review. Optofluidic biolasers are emerging as a highly sensitive way to measure changes in biol. mols. Biolasers, which incorporate biol. material into the gain medium and contain an optical cavity in a fluidic environment, can use the amplification that occurs during laser generation to quantify tiny changes in biol. processes in the gain medium. We describe the principle of the optofluidic biolaser, review recent progress and provide our outlooks on potential applications and directions for developing this technol.
17. 17
  Pan, T.; Lu, D.; Xin, H.; Li, B. Biophotonic probes for bio-detection and imaging. Light: Sci. Appl. 2021, 10, 124, DOI: 10.1038/s41377-021-00561-2
  17
  Biophotonic probes for bio-detection and imaging
  Pan, Ting; Lu, Dengyun; Xin, Hongbao; Li, Baojun
  Light: Science & Applications (2021), 10 (1), 124CODEN: LSAIAZ; ISSN:2047-7538. (Nature Research)
  A review. The rapid development of biophotonics and biomedical sciences makes a high demand on photonic structures to be interfaced with biol. systems that are capable of manipulating light at small scales for sensitive detection of biol. signals and precise imaging of cellular structures. However, conventional photonic structures based on artificial materials (either inorg. or toxic org.) inevitably show incompatibility and invasiveness when interfacing with biol. systems. The design of biophotonic probes from the abundant natural materials, particularly biol. entities such as virus, cells and tissues, with the capability of multifunctional light manipulation at target sites greatly increases the biocompatibility and minimizes the invasiveness to biol. microenvironment. In this review, advances in biophotonic probes for bio-detection and imaging are reviewed. We emphatically and systematically describe biol. entities-based photonic probes that offer appropriate optical properties, biocompatibility, and biodegradability with different optical functions from light generation, to light transportation and light modulation. Three representative biophotonic probes, i.e., biol. lasers, cell-based biophotonic waveguides and bio-microlenses, are reviewed with applications for bio-detection and imaging. Finally, perspectives on future opportunities and potential improvements of biophotonic probes are also provided.
18. 18
  Caixeiro, S. Local Sensing of Absolute Refractive Index During Protein-Binding using Microlasers with Spectral Encoding. Adv. Opt. Mater. 2023, 11, 2300530, DOI: 10.1002/adom.202300530
  There is no corresponding record for this reference.
19. 19
  Schubert, M. Monitoring contractility in cardiac tissue with cellular resolution using biointegrated microlasers. Nat. Photonics 2020, 14, 452– 458, DOI: 10.1038/s41566-020-0631-z
  19
  Monitoring contractility in cardiac tissue with cellular resolution using biointegrated microlasers
  Schubert, Marcel; Woolfson, Lewis; Barnard, Isla R. M.; Dorward, Amy M.; Casement, Becky; Morton, Andrew; Robertson, Gavin B.; Appleton, Paul L.; Miles, Gareth B.; Tucker, Carl S.; Pitt, Samantha J.; Gather, Malte C.
  Nature Photonics (2020), 14 (7), 452-458CODEN: NPAHBY; ISSN:1749-4885. (Nature Research)
  Abstr.: The contractility of cardiac cells is a key parameter that describes the biomech. characteristics of the beating heart, but functional monitoring of three-dimensional cardiac tissue with single-cell resoln. remains a major challenge. Here, we introduce microscopic whispering-gallery-mode lasers into cardiac cells to realize all-optical recording of transient cardiac contraction profiles with cellular resoln. The brilliant emission and high spectral sensitivity of microlasers to local changes in refractive index enable long-term tracking of individual cardiac cells, monitoring of drug administration, accurate measurements of organ-scale contractility in live zebrafish, and robust contractility sensing through hundreds of micrometres of rat heart tissue. Our study reveals changes in sarcomeric protein d. as an underlying factor to cardiac contraction. More broadly, the use of novel micro- and nanoscopic lasers as non-invasive, biointegrated optical sensors brings new opportunities to monitor a wide range of physiol. parameters with cellular resoln.
20. 20
  Caixeiro, S.; Gaio, M.; Marelli, B.; Omenetto, F. G.; Sapienza, R. Silk-Based Biocompatible Random Lasing. Adv. Opt. Mater. 2016, 4, 998– 1003, DOI: 10.1002/adom.201600185
  20
  Silk-Based Biocompatible Random Lasing
  Caixeiro, Soraya; Gaio, Michele; Marelli, Benedetto; Omenetto, Fiorenzo G.; Sapienza, Riccardo
  Advanced Optical Materials (2016), 4 (7), 998-1003CODEN: AOMDAX; ISSN:2195-1071. (Wiley-VCH Verlag GmbH & Co. KGaA)
  Here, a biocompatible random laser made entirely of doped silk, functional in aq. media, showing clear threshold behavior and spectral narrowing are demonstrated. Furthermore, the device is capable of probing changes in a chem. environment, namely, pH, due to the intrinsic nonlinear response and the large spectral purity.
21. 21
  Wang, Y. Demonstration of intracellular real-time molecular quantification via FRET-enhanced optical microcavity. Nat. Commun. 2022, 13, 6685, DOI: 10.1038/s41467-022-34547-4
  There is no corresponding record for this reference.
22. 22
  Duan, R.; Hao, X.; Li, Y.; Li, H. Detection of acetylcholinesterase and its inhibitors by liquid crystal biosensor based on whispering gallery mode. Sensors Actuators, B Chem. 2020, 308, 127672, DOI: 10.1016/j.snb.2020.127672
  There is no corresponding record for this reference.
23. 23
  Schubert, M. Lasing within Live Cells Containing Intracellular Optical Microresonators for Barcode-Type Cell Tagging and Tracking. Nano Lett. 2015, 15, 5647– 5652, DOI: 10.1021/acs.nanolett.5b02491
  23
  Lasing within Live Cells Containing Intracellular Optical Microresonators for Barcode-Type Cell Tagging and Tracking
  Schubert, Marcel; Steude, Anja; Liehm, Philipp; Kronenberg, Nils M.; Karl, Markus; Campbell, Elaine C.; Powis, Simon J.; Gather, Malte C.
  Nano Letters (2015), 15 (8), 5647-5652CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)
  The authors report on a laser that is fully embedded within a single live cell. By harnessing natural endocytosis of the cell, the authors introduce a fluorescent whispering gallery mode (WGM) microresonator into the cell cytoplasm. On pumping with nanojoule light pulses, green laser emission was generated inside the cells. The authors' approach can be applied to different cell types, and cells with microresonators remain viable for weeks under std. conditions. The characteristics of the lasing spectrum provide each cell with a barcode-type label which enables uniquely identifying and tracking individual migrating cells. Self-sustained lasing from cells paves the way to new forms of cell tracking, intracellular sensing, and adaptive imaging.
24. 24
  Martino, N. Wavelength-encoded laser particles for massively multiplexed cell tagging. Nat. Photonics 2019, 13, 720– 727, DOI: 10.1038/s41566-019-0489-0
  24
  Wavelength-encoded laser particles for massively multiplexed cell tagging
  Martino, Nicola; Kwok, Sheldon J. J.; Liapis, Andreas C.; Forward, Sarah; Jang, Hoon; Kim, Hwi-Min; Wu, Sarah J.; Wu, Jiamin; Dannenberg, Paul H.; Jang, Sun-Joo; Lee, Yong-Hee; Yun, Seok-Hyun
  Nature Photonics (2019), 13 (10), 720-727CODEN: NPAHBY; ISSN:1749-4885. (Nature Research)
  Large-scale single-cell analyses have become increasingly important given the role of cellular heterogeneity in complex biol. systems. However, no techniques at present enable optical imaging of uniquely tagged individual cells. Fluorescence-based approaches can distinguish only a small no. of distinct cells or cell groups at a time because of spectral crosstalk between conventional fluorophores. Here we investigate large-scale cell tracking using intracellular laser particles as imaging probes that emit coherent laser light with a characteristic wavelength. Made of silica-coated semiconductor microcavities, these laser particles have single-mode emission over a broad range from 1,170 nm to 1,580 nm with sub-nanometer linewidths, enabling massive spectral multiplexing. We explore the stability and biocompatibility of these probes in vitro and their utility for wavelength-multiplexed cell tagging and imaging. We demonstrate real-time tracking of thousands of individual cells in a three-dimensional tumor model over several days, showing different behavioral phenotypes.
25. 25
  Fikouras, A. H. Non-obstructive intracellular nanolasers. Nat. Commun. 2018, 9, 4817, DOI: 10.1038/s41467-018-07248-0
  25
  Non-obstructive intracellular nanolasers
  Fikouras Alasdair H; Schubert Marcel; Karl Markus; Kumar Jothi D; Di Falco Andrea; Gather Malte C; Powis Simon J
  Nature communications (2018), 9 (1), 4817 ISSN:.
  Molecular dyes, plasmonic nanoparticles and colloidal quantum dots are widely used in biomedical optics. Their operation is usually governed by spontaneous processes, which results in broad spectral features and limited signal-to-noise ratio, thus restricting opportunities for spectral multiplexing and sensing. Lasers provide the ultimate spectral definition and background suppression, and their integration with cells has recently been demonstrated. However, laser size and threshold remain problematic. Here, we report on the design, high-throughput fabrication and intracellular integration of semiconductor nanodisk lasers. By exploiting the large optical gain and high refractive index of GaInP/AlGaInP quantum wells, we obtain lasers with volumes 1000-fold smaller than the eukaryotic nucleus (Vlaser < 0.1 μm(3)), lasing thresholds 500-fold below the pulse energies typically used in two-photon microscopy (Eth ≈ 0.13 pJ), and excellent spectral stability (<50 pm wavelength shift). Multiplexed labeling with these lasers allows cell-tracking through micro-pores, thus providing a powerful tool to study cell migration and cancer invasion.
26. 26
  Dalaka, E. Deformable microlaser force sensing. Light: Sci. Appl. 2024, 13, 129, DOI: 10.1038/s41377-024-01471-9
  There is no corresponding record for this reference.
27. 27
  Pirnat, G.; Marinčič, M.; Ravnik, M.; Humar, M. Quantifying local stiffness and forces in soft biological tissues using droplet optical microcavities. Proc. Natl. Acad. Sci. U. S. A. 2024, 121 (4), e2314884121 DOI: 10.1073/pnas.2314884121
  There is no corresponding record for this reference.
28. 28
  Leonetti, M. Optical gain in DNA-DCM for lasing in photonic materials. Opt. Lett. 2009, 34, 3764– 3766, DOI: 10.1364/OL.34.003764
  28
  Optical gain in DNA-DCM for lasing in photonic materials
  Leonetti, Marco; Sapienza, Riccardo; Ibisate, Marta; Conti, Claudio; Lopez, Cefe
  Optics Letters (2009), 34 (24), 3764-3766CODEN: OPLEDP; ISSN:0146-9592. (Optical Society of America)
  We present a detailed study of the gain length in an active medium obtained by doping of DNA strands with 4-(dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran dye mols. The superior thermal stability of the composite and its low quenching permit one to obtain an optical gain coeff. larger than 300 cm-1. We also demonstrate that such an active material is feasible for the infiltration into photonic nanostructures, allowing one to obtain fluorescent photonic crystals and promising lasing properties.
29. 29
  Lee, W.; Chen, Q.; Fan, X.; Yoon, D. K. Digital DNA detection based on a compact optofluidic laser with ultra-low sample consumption. Lab Chip 2016, 16, 4770– 4776, DOI: 10.1039/C6LC01258B
  29
  Digital DNA detection based on a compact optofluidic laser with ultra-low sample consumption
  Lee, Wonsuk; Chen, Qiushu; Fan, Xudong; Yoon, Dong Ki
  Lab on a Chip (2016), 16 (24), 4770-4776CODEN: LCAHAM; ISSN:1473-0189. (Royal Society of Chemistry)
  DNA lasers self-amplify optical signals from a DNA analyte as well as thermodn. differences between sequences, allowing quasi-digital DNA detection. However, these systems have drawbacks, such as relatively large sample consumption and complicated dye labeling. Moreover, although the lasing signal can detect the target DNA, it is superimposed on an unintended fluorescence background, which persists for non-target DNA samples as well. From an optical point of view, it is thus not truly digital detection and requires spectral anal. to identify the target. In this work, we propose and demonstrate an optofluidic laser that has a single layer of DNA mols. as the gain material. A target DNA produces intensive laser emission comparable to existing DNA lasers, while any unnecessary fluorescence background is successfully suppressed. As a result, the target DNA can be detected with a single laser pulse, in a truly digital manner. Since the DNA mols. cover only a single layer on the surface of the laser microcavity, the DNA sample consumption is a few orders of magnitude lower than that of existing DNA lasers. Furthermore, the DNA mols. are stained by simply immersing the microcavity in the intercalating dye soln., and thus the proposed DNA laser is free of any complex dye-labeling process prior to anal.
30. 30
  Tanwar, S.; Kaur, V.; Kaur, G.; Sen, T. Broadband SERS Enhancement by DNA Origami Assembled Bimetallic Nanoantennas with Label-Free Single Protein Sensing. J. Phys. Chem. Lett. 2021, 12, 8141– 8150, DOI: 10.1021/acs.jpclett.1c02272
  30
  Broadband SERS Enhancement by DNA Origami Assembled Bimetallic Nanoantennas with Label-Free Single Protein Sensing
  Tanwar, Swati; Kaur, Vishaldeep; Kaur, Gagandeep; Sen, Tapasi
  Journal of Physical Chemistry Letters (2021), 12 (33), 8141-8150CODEN: JPCLCD; ISSN:1948-7185. (American Chemical Society)
  Engineering hotspots in surface-enhanced Raman spectroscopy (SERS) through precisely controlled assembly of plasmonic nanostructures capable of expanding intense field enhancement are highly desirable to enhance the potentiality of SERS as a label-free optical tool for single mol. detection. Inspired by DNA origami technique, we constructed plasmonic dimer nanoantennas with a tunable gap decorated with Ag-coated Au nanostars on origami. Herein, we demonstrate the single-mol. SERS enhancements of three dyes with emission in different spectral regions after incorporation of single dye mols. in between two nanostars. The enhancement factors (EFs) achieved in the range of 109-1010 for all the single dye mols., under both resonant and nonresonant excitation conditions, would enable enhanced photostability during time-series measurement. We further successfully explored the potential of our designed nanoantennas to accommodate and detect a single thrombin protein mol. after selective placement in the wide nanogap of 10 nm. Our results suggest that such nanoantennas can serve as a broadband SERS enhancer and enable specific detection of target biol. mols. with single-mol. sensitivity.
31. 31
  Das, M.; Shim, K. H.; An, S. S. A.; Yi, D. K. Review on gold nanoparticles and their applications. Toxicol. Environ. Health Sci. 2011, 3, 193– 205, DOI: 10.1007/s13530-011-0109-y
  There is no corresponding record for this reference.
32. 32
  Dreaden, E. C.; Alkilany, A. M.; Huang, X.; Murphy, C. J.; El-Sayed, M. A. The golden age: Gold nanoparticles for biomedicine. Chem. Soc. Rev. 2012, 41, 2740– 2779, DOI: 10.1039/C1CS15237H
  32
  The golden age: gold nanoparticles for biomedicine
  Dreaden, Erik C.; Alkilany, Alaaldin M.; Huang, Xiaohua; Murphy, Catherine J.; El-Sayed, Mostafa A.
  Chemical Society Reviews (2012), 41 (7), 2740-2779CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)
  A review. Gold nanoparticles have been used in biomedical applications since their first colloidal syntheses more than three centuries ago. However, over the past two decades, their beautiful colors and unique electronic properties have also attracted tremendous attention due to their historical applications in art and ancient medicine and current applications in enhanced optoelectronics and photovoltaics. In spite of their modest alchem. beginnings, gold nanoparticles exhibit phys. properties that are truly different from both small mols. and bulk materials, as well as from other nanoscale particles. Their unique combination of properties is just beginning to be fully realized in range of medical diagnostic and therapeutic applications. This crit. review will provide insights into the design, synthesis, functionalization, and applications of these artificial mols. in biomedicine and discuss their tailored interactions with biol. systems to achieve improved patient health. Further, we provide a survey of the rapidly expanding body of literature on this topic and argue that gold nanotechnol.-enabled biomedicine is not simply an act of gilding the (nanomedicinal) lily', but that a new Golden Age' of biomedical nanotechnol. is truly upon us. Moving forward, the most challenging nanoscience ahead of us will be to find new chem. and phys. methods of functionalizing gold nanoparticles with compds. that can promote efficient binding, clearance, and biocompatibility and to assess their safety to other biol. systems and their long-term term effects on human health and reprodn. (472 refs.).
33. 33
  Hao, Y.; Fang, L.; Deng, Z. Solvo-driven dimeric nanoplasmon coupling under DNA direction. CCS Chem. 2021, 3, 1359– 1367, DOI: 10.31635/ccschem.020.202000290
  33
  Solvo-driven dimeric nanoplasmon coupling under DNA direction
  Hao, Yan; Fang, Lingling; Deng, Zhaoxiang
  CCS Chemistry (2021), 3 (4), 1359-1367CODEN: CCCHB2 ISSN:. (Chinese Chemical Society)
  Strong coupling is a prerequisite for nanoassemblies to deliver functions and applications unrealizable by noninteracting building units. DNA-Directed metamaterials, albeit highly programmable, often show negligible interunit coupling and accordingly limited functions. Herein a simple but highly effective solvent-driven process for dimeric plasmon coupling under DNA's guidance is reported. The DNA is responsible for a proximity control of plasmonic units to undergo electromagnetic hybridization. This process is inspired by a spontaneous formation of nanoparticle chains in less polar water-miscible solvents. The resulting 1.25 nm surface sepn. is insensitive to DNA linker length as well as solvent/water ratios above a certain threshold, consistent with a Van der Waals colloidal bonding model. Our strategy avoids surface contamination to the nanoassemblies with the DNA linker in position to ensure coupling selectivity and reversibility. The cooperative but orthogonal roles played by DNA and the org. solvents promise bottom-up materials and devices with prescribed functions.
34. 34
  Wang, P. Magnetic Plasmon Networks Programmed by Molecular Self-Assembly. Adv. Mater. 2019, 31, 1901364, DOI: 10.1002/adma.201901364
  There is no corresponding record for this reference.
35. 35
  Xie, M.; Jiang, J.; Chao, J. DNA-Based Gold Nanoparticle Assemblies: From Structure Constructions to Sensing Applications. Sensors 2023, 23, 9229, DOI: 10.3390/s23229229
  There is no corresponding record for this reference.
36. 36
  Park, D. J. Directional emission from dye-functionalized plasmonic DNA superlattice microcavities. Proc. Natl. Acad. Sci. U. S. A. 2017, 114, 457– 461, DOI: 10.1073/pnas.1619802114
  36
  Directional emission from dye-functionalized plasmonic DNA superlattice microcavities
  Park, Daniel J.; Ku, Jessie C.; Sun, Lin; Lethiec, Clotilde M.; Stern, Nathaniel P.; Schatz, George C.; Mirkin, Chad A.
  Proceedings of the National Academy of Sciences of the United States of America (2017), 114 (3), 457-461CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)
  Three-dimensional plasmonic superlattice microcavities, made from programmable atom equiv. comprising Au nanoparticles functionalized with DNA, are used as a testbed to study directional light emission. DNA-guided nanoparticle colloidal crystn. allows for the formation of micrometer-scale single-crystal bcc. Au nanoparticle superlattices, with dye mols. coupled to the DNA strands that link the particles together, as a rhombic dodecahedron. Encapsulation in SiO2 allows 1 to create robust architectures with the plasmonically active particles and dye mols. fixed in space. At the micrometer scale, the anisotropic rhombic dodecahedron crystal habit couples with photonic modes to give directional light emission. At the nanoscale, the interaction between the dye dipoles and surface plasmons can be finely tuned by coupling the dye mols. to specific sites of the DNA particle-linker strands, thereby modulating dye-nanoparticle distance (3 different positions are studied). The ability to control dye position with subnanometer precision allows 1 to systematically tune plasmon-excition interaction strength and decay lifetime, the results of which were supported by electrodynamics calcns. that span length scales from nanometers to micrometers. The unique ability to control surface plasmon/exciton interactions within such superlattice microcavities will catalyze studies involving quantum optics, plasmon laser physics, strong coupling, and nonlinear phenomena.
37. 37
  Wu, F. C.; Wu, Y.; Niu, Z.; Vollmer, F. Ratiometric detection of oligonucleotide stoichiometry on multi-functional gold nanoparticles by whispering gallery mode biosensing. Analyst 2015, 140, 2969– 2972, DOI: 10.1039/C5AN00179J
  There is no corresponding record for this reference.
38. 38
  Li, L.; Zhang, Y.-n.; Zheng, W.; Li, X.; Zhao, Y. Optical fiber SPR biosensor based on gold nanoparti-cle amplification for DNA hybridization detection. Talanta 2022, 247, 123599, DOI: 10.1016/j.talanta.2022.123599
  There is no corresponding record for this reference.
39. 39
  Baaske, M. D.; Foreman, M. R.; Vollmer, F. Single-molecule nucleic acid interactions monitored on a label-free microcavity biosensor platform. Nat. Nanotechnol. 2014, 9, 933– 939, DOI: 10.1038/nnano.2014.180
  39
  Single-molecule nucleic acid interactions monitored on a label-free microcavity biosensor platform
  Baaske, Martin D.; Foreman, Matthew R.; Vollmer, Frank
  Nature Nanotechnology (2014), 9 (11), 933-939CODEN: NNAABX; ISSN:1748-3387. (Nature Publishing Group)
  Biosensing relies on the detection of mols. and their specific interactions. It is therefore highly desirable to develop transducers exhibiting ultimate detection limits. Microcavities are an exemplary candidate technol. for demonstrating such a capability in the optical domain and in a label-free fashion. Addnl. sensitivity gains, achievable by exploiting plasmon resonances, promise biosensing down to the single-mol. level. Here, we introduce a biosensing platform using optical microcavity-based sensors that exhibits single-mol. sensitivity and is selective to specific single binding events. Whispering gallery modes in glass microspheres are used to leverage plasmonic enhancements in gold nanorods for the specific detection of nucleic acid hybridization, down to single 8-mer oligonucleotides. Detection of single intercalating small mols. confirms the observation of single-mol. hybridization. Matched and mismatched strands are discriminated by their interaction kinetics. Our platform allows us to monitor specific mol. interactions transiently, hence mitigating the need for high binding affinity and avoiding permanent binding of target mols. to the receptors. Sensor lifetime is therefore increased, allowing interaction kinetics to be statistically analyzed.
40. 40
  de Planell-Saguer, M.; Rodicio, M. C.; Mourelatos, Z. Rapid in situ codetection of noncoding RNAs and proteins in cells and formalin-fixed paraffin-embedded tissue sections without protease treatment. Nat. Protoc. 2010, 5, 1061– 1073, DOI: 10.1038/nprot.2010.62
  There is no corresponding record for this reference.
41. 41
  Nuovo, G. J.; Lee, E. J.; Lawler, S.; Godlewski, J.; Schmittgen, T. D. In situ detection of mature microRNAs by labeled extension on ultramer templates. Biotechniques 2009, 46, 115– 126, DOI: 10.2144/000113068
  There is no corresponding record for this reference.
42. 42
  Pena, J. T. G. miRNA in situ hybridization in formaldehyde and EDC - Fixed tissues. Nat. Methods 2009, 6, 139– 141, DOI: 10.1038/nmeth.1294
  42
  miRNA in situ hybridization in formaldehyde and EDC-fixed tissues
  Pena, John T. G.; Sohn-Lee, Cherin; Rouhanifard, Sara H.; Ludwig, Janos; Hafner, Markus; Mihailovic, Aleksandra; Lim, Cindy; Holoch, Daniel; Berninger, Philipp; Zavolan, Mihaela; Tuschl, Thomas
  Nature Methods (2009), 6 (2), 139-141CODEN: NMAEA3; ISSN:1548-7091. (Nature Publishing Group)
  MicroRNAs are small regulatory RNAs with many biol. functions and disease assocns. The authors showed that in situ hybridization (ISH) using conventional formaldehyde fixation results in substantial microRNA loss from mouse tissue sections, which can be prevented by fixation with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide that irreversibly immobilizes the microRNA at its 5' phosphate. The authors detd. optimal hybridization parameters for 130 locked nucleic acid probes by recording nucleic acid melting temp. during ISH.
43. 43
  Titze, V. M. Hyperspectral confocal imaging for high-throughput readout and analysis of bio-integrated microlasers. Nat. Protoc. 2024, 19, 928– 959, DOI: 10.1038/s41596-023-00924-6
  There is no corresponding record for this reference.
44. 44
  Foreman, M. R.; Swaim, J. D.; Vollmer, F. Whispering gallery mode sensors. Adv. Opt. Photonics 2015, 7, 168– 240, DOI: 10.1364/AOP.7.000168
  44
  Whispering gallery mode sensors
  Foreman, Matthew R.; Swaim, Jon D.; Vollmer, Frank
  Advances in Optics and Photonics (2015), 7 (2), 168-240CODEN: AOPAC7; ISSN:1943-8206. (Optical Society of America)
  We present a comprehensive overview of sensor technol. exploiting optical whispering gallery mode (WGM) resonances. After a short introduction we begin by detailing the fundamental principles and theory of WGMs in optical microcavities and the transduction mechanisms frequently employed for sensing purposes. Key recent theor. contributions to the modeling and anal. of WGM systems are highlighted. Subsequently we review the state of the art of WGM sensors by outlining efforts made to date to improve current detection limits. Proposals in this vein are numerous and range, for example, from plasmonic enhancements and active cavities to hybrid optomech. sensors, which are already working in the shot noise limited regime. In parallel to furthering WGM sensitivity, efforts to improve the time resoln. are beginning to emerge. We therefore summarize the techniques being pursued in this vein. Ultimately WGM sensors aim for real-world applications, such as measurements of force and temp., or alternatively gas and biosensing. Each such application is thus reviewed in turn, and important achievements are discussed. Finally, we adopt a more forward-looking perspective and discuss the outlook of WGM sensors within both a phys. and biol. context and consider how they may yet push the detection envelope further.
45. 45
  Owczarzy, R.; Moreira, B. G.; You, Y.; Behlke, M. A.; Wälder, J. A. Predicting stability of DNA duplexes in solutions containing magnesium and monovalent cations. Biochemistry 2008, 47, 5336– 5353, DOI: 10.1021/bi702363u
  45
  Predicting Stability of DNA Duplexes in Solutions Containing Magnesium and Monovalent Cations
  Owczarzy, Richard; Moreira, Bernardo G.; You, Yong; Behlke, Mark A.; Walder, Joseph A.
  Biochemistry (2008), 47 (19), 5336-5353CODEN: BICHAW; ISSN:0006-2960. (American Chemical Society)
  Accurate predictions of DNA stability in physiol. and enzyme buffers are important for the design of many biol. and biochem. assays. We therefore investigated the effects of magnesium, potassium, sodium, Tris ions, and deoxynucleoside triphosphates on melting profiles of duplex DNA oligomers and collected large melting data sets. An empirical correction function was developed that predicts melting temps., transition enthalpies, entropies, and free energies in buffers contg. magnesium and monovalent cations. The new correction function significantly improves the accuracy of predictions and accounts for ion concn., G-C base pair content, and length of the oligonucleotides. The competitive effects of potassium and magnesium ions were characterized. If the concn. ratio of [Mg2+]0.5/[Mon+] is less than 0.22 M-1/2, monovalent ions (K+, Na+) are dominant. Effects of magnesium ions dominate and det. duplex stability at higher ratios. Typical reaction conditions for PCR and DNA sequencing (1.5-5 mM magnesium and 20-100 mM monovalent cations) fall within this range. Conditions were identified where monovalent and divalent cations compete and their stability effects are more complex. When duplexes denature, some of the Mg2+ ions assocd. with the DNA are released. The no. of released magnesium ions per phosphate charge is sequence dependent and decreases surprisingly with increasing oligonucleotide length.
46. 46
  Morris, D. L. DNA-bound metal ions: Recent developments. Biomol. Concepts 2014, 5, 397– 407, DOI: 10.1515/bmc-2014-0021
  46
  DNA-bound metal ions: recent developments
  Morris, Daniel L., Jr.
  Biomolecular Concepts (2014), 5 (5), 397-407CODEN: BCIOB8; ISSN:1868-5021. (Walter de Gruyter GmbH)
  A review. The affinity of metal ions for DNA is logical considering that the structure of DNA includes a phosphate backbone with a net-neg. charge, a deoxyribose sugar with O atoms, and purine and pyrimidine bases that contain O and N atoms. DNA-metal ion interactions encompass a large area of research that ranges from the most fundamental characterization of DNA-metal ion binding to the role of DNA-bound metal ions in disease and human health. Alternative DNA base pairing mediated by metal binding is also being investigated and manipulated for applications in logic gates, mol. machines, and nanotechnol. This review highlights recent work aimed at understanding interactions of redox-active metal ions with DNA that provides a better understanding of the mechanisms by which various types of oxidative DNA damage (strand breakage and base modifications) occur. Antioxidants that mitigate oxidative DNA damage by coordinating metal ions that produce reactive oxygen species are addressed, as well as recent work on the effect of DNA-metal ion interactions and the efficacy of quinolone-based antibacterial drugs. Recent advances in metal-mediated base pairing that triggers conformational changes in DNA structure for use as selective metal ion sensors and novel nanotechnol. applications are also included.
47. 47
  Wetmur, J. G.; Fresco, J. DNA probes: Applications of the principles of nucleic acid hybridization. Crit. Rev. Biochem. Mol. Biol. 1991, 26, 227– 259, DOI: 10.3109/10409239109114069
  47
  DNA probes: applications of the principles of nucleic acid hybridization
  Wetmur, James G.
  Critical Reviews in Biochemistry and Molecular Biology (1991), 26 (3-4), 227-59CODEN: CRBBEJ; ISSN:1040-9238.
  A review with 222 refs. Nucleic acid hybridization with a labeled probe is the only practical way to detect a complementary target sequence in a complex nucleic acid mixt. The 1st section of this article covers quant. aspects of nucleic acid hybridization, thermodn. and kinetics. The probes considered are oligonucleotides or polynucleotides, DNA or RNA, single- or double-stranded, and natural or modified, either in the nucleotide bases or in the backbone. The hybridization products are duplexes or triplexes formed with targets in soln. or on solid supports. Addnl, topics include hybridization acceleration and reactions involving branch migration. The second section deals with synthesis or biosynthesis and detection of labeled probes, with a discussion of their sensitivity and specificity limits. Direct labeling is illustrated with radioactive probes. The discussion of indirect labels begins with biotinylated probes as prototypes. Reporter groups considered includ radioactive, fluorescent, and chemiluminescent nucleotides, as well as enzymes with colorimetric, fluorescent, and luminescent substrates.
48. 48
  Draper, D. E. Folding of RNA tertiary structure: Linkages between backbone phosphates, ions, and water. Biopolymers 2013, 99, 1105– 1113, DOI: 10.1002/bip.22249
  48
  Folding of RNA tertiary structure: Linkages between backbone phosphates, ions, and water
  Draper, David E.
  Biopolymers (2013), 99 (12), 1105-1113CODEN: BIPMAA; ISSN:0006-3525. (John Wiley & Sons, Inc.)
  A review. The functional forms of many RNAs have compact architectures. The placement of phosphates within such structures must be influenced not only by the strong electrostatic repulsion between phosphates, but also by networks of interactions between phosphates, water, and mobile ions. This review first explores what has been learned of the basic thermodn. constraints on these arrangements from studies of hydration and ions in simple DNA mols., and then gives an overview of what is known about ion and water interactions with RNA structures. A brief survey of RNA crystal structures identifies several interesting architectures in which closely spaced phosphates share hydration shells or phosphates are buried in environments that provide intramol. hydrogen bonds or site-bound cations. Formation of these structures must require strong coupling between the uptake of ions and release of water. © 2013 Wiley Periodicals, Inc. Biopolymers 99: 1105-1113, 2013.
49. 49
  Tan, Z. J.; Chen, S. J. Nucleic acid helix stability: Effects of salt concentration, cation valence and size, and chain length. Biophys. J. 2006, 90, 1175– 1190, DOI: 10.1529/biophysj.105.070904
  49
  Nucleic acid helix stability: effects of salt concentration, cation valence and size, and chain length
  Tan, Zhi-Jie; Chen, Shi-Jie
  Biophysical Journal (2006), 90 (4), 1175-1190CODEN: BIOJAU; ISSN:0006-3495. (Biophysical Society)
  Metal ions play crucial roles in thermal stability and folding kinetics of nucleic acids. For ions (esp. multivalent ions) in the close vicinity of nucleic acid surface, interion correlations and ion-binding mode fluctuations may be important. Poisson-Boltzmann theory ignores these effects whereas the recently developed tightly bound ion (TBI) theory explicitly accounts for these effects. Extensive exptl. data demonstrate that the TBI theory gives improved predictions for multivalent ions (e.g., Mg2+) than the Poisson-Boltzmann theory. In this study, we use the TBI theory to investigate how the metal ions affect the folding stability of B-DNA helixes. We quant. evaluate the effects of ion concn., ion size and valence, and helix length on the helix stability. Moreover, we derive practically useful anal. formulas for the thermodn. parameters as functions of finite helix length, ion type, and ion concn. We find that the helix stability is additive for high ion concn. and long helix and nonadditive for low ion concn. and short helix. All these results are tested against and supported by extensive exptl. data.
50. 50
  Wang, G.; Vasquez, K. M. Impact of alternative DNA structures on DNA damage, DNA repair, and genetic instability. DNA Repair (Amst). 2014, 19, 143– 151, DOI: 10.1016/j.dnarep.2014.03.017
  There is no corresponding record for this reference.
51. 51
  Shan, L. Hairpin DNA-Based Nanomaterials for Tumor Targeting and Synergistic Therapy. Int. J. Nanomedicine 2024, 19, 5781– 5792, DOI: 10.2147/IJN.S461774
  There is no corresponding record for this reference.
52. 52
  Epstein, J. R.; Biran, I.; Walt, D. R. Fluorescence-Based Nucleic Acid Detection and Microarrays ; 2002; Vol. 469.
  There is no corresponding record for this reference.
53. 53
  Caixeiro, S., Dörrenhaus, R., Popczyk, A., Schubert, M., Kath-Schorr, S., Gather, M. C., in press. Dataset for “DNA Sensing with Whispering Gallery Mode Microlaser”. Bath: University of Bath Research Data Archive. DOI: 10.15125/BATH-01497 .
  There is no corresponding record for this reference.
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DNA Sensing with Whispering Gallery Mode Microlasers
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DNA Sensing with Whispering Gallery Mode Microlasers
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