Download Hi-Res ImageDownload to MS-PowerPointCite This:ACS Appl. Mater. Interfaces 2017, 9, 14, 12272-12281

Research ArticleMarch 23, 2017

Oligonucleotide Sensor Based on Selective Capture of Upconversion Nanoparticles Triggered by Target-Induced DNA Interstrand Ligand Reaction
Click to copy article linkArticle link copied!

View Author Information

Open PDF Supporting Information (1)

ACS Applied Materials & Interfaces

Cite this: ACS Appl. Mater. Interfaces 2017, 9, 14, 12272–12281

Click to copy citationCitation copied!

https://doi.org/10.1021/acsami.7b00575

Published March 23, 2017

Abstract

Click to copy section linkSection link copied!

We present a sensor that exploits the phenomenon of upconversion luminescence to detect the presence of specific sequences of small oligonucleotides such as miRNAs among others. The sensor is based on NaYF₄:Yb,Er@SiO₂ nanoparticles functionalized with ssDNA that contain azide groups on the 3′ ends. In the presence of a target sequence, interstrand ligation is possible via the click-reaction between one azide of the upconversion probe and a DBCO-ssDNA-biotin probe present in the solution. As a result of this specific and selective process, biotin is covalently attached to the surface of the upconversion nanoparticles. The presence of biotin on the surface of the nanoparticles allows their selective capture on a streptavidin-coated support, giving a luminescent signal proportional to the amount of target strands present in the test samples. With the aim of studying the analytical properties of the sensor, total RNA samples were extracted from healthy mosquitoes and were spiked-in with a specific target sequence at different concentrations. The result of these experiments revealed that the sensor was able to detect 10^–17 moles per well (100 fM) of the target sequence in mixtures containing 100 ng of total RNA per well. A similar limit of detection was found for spiked human serum samples, demonstrating the suitability of the sensor for detecting specific sequences of small oligonucleotides under real conditions. In contrast, in the presence of noncomplementary sequences or sequences having mismatches, the luminescent signal was negligible or conspicuously reduced.

Subjects

Keywords

1 Introduction

Click to copy section linkSection link copied!

In recent years, the advances in deep sequencing techniques have facilitated the discovery of the presence of noncoding nucleic acids, such as microRNAs (miRNAs), small-interfering RNAs (siRNAs), and Piwi-interacting RNAs (piRNAs), involved in the regulation of gene expression, modulating protein production, (1, 2) and lately used as biomarkers for different diseases. Furthermore, these biomarkers appear at the very beginning of the disease, facilitating early diagnostics. (3, 4) Among them, miRNAs are the best known due to their potential role as biomarkers in cancer, cardiovascular diseases, (5, 6) as well as in many viral infections such as HIV-1, (7) Ebola, (8) and so forth. Other small RNAs like piRNAs, small nucleolar RNAs, and small nuclear RNAs are also gaining support as biomarkers for male infertility (9) or for viral infections like that produced by DENV2. (10) However, in most cases, proper diagnosis of disease requires the analysis of multiple sequences (multiplexing) by qRT-PCR or next-generation sequencing, limiting its application to wealthy regions as these techniques require specific labs, trained personnel, and expensive reagents. In addition, these techniques are time consuming and difficult to apply as a screening tool, especially in developing countries. These drawbacks have prompted scientists to investigate alternative methods that could be used as screening tools in the detection of these oligonucleotides without the requirement of enzymatic transcription and amplification. Among the new technologies, the use of molecular beacons based on upconversion nanoparticles has opened the possibility to create highly sensitive systems capable of analyzing the presence of these oligonucleotides at extremely low concentrations in a fast, cheap and easy way. (11-18) These systems exploit the use of lanthanide-doped nanoparticles, which can absorb two or more low energy photons and emit one at higher energy. (19, 20) In addition, these nanoparticles have interesting photoluminescent properties, like high photostability, the absence of blinking and photobleaching, along with large anti-Stokes shifts, which allow the creation of robust analytical systems with low backgrounds and high signal-to-noise ratios. (19, 21-26) Furthermore, the narrow emission bands exhibited by these nanoparticles and the possibility to tune their emission wavelengths make them ideal candidates to be used for multiplexed analytical systems (27-29) in immunoassays (ULISA) (30) where the upconversion nanoparticles (UCNPs) are linked to antibodies or aptamers (25) as reporters. In these analytical systems, the target and the functionalized UCNP are captured on a solid support giving a signal proportional to the amount of target. The high affinity and specificity between the UCNPs and the targets yield highly thermodynamically stable complexes, which allows stringent cleaning processes of the capture-surface that permit washing away of any nonspecifically physisorbed UCNPs. This yields low detection limits comparable to those obtained by enzymatic amplification techniques like ELISA. However, when this strategy is applied to the detection of small oligonucleotides, like miRNAs (20–30 bp), a major problem related to the low thermodynamic stability of the complexes prevents the use of stringent cleaning steps, which in turn hampers target detection.

In this work, we present an analytical system that allows the detection of oligonucleotides (RNA or DNA) on a solid support, which is based on ssDNA functionalized NaYF₄:Yb,Er@SiO₂ nanoparticles that contain azide groups on the 3′ ends. In the presence of a target sequence, an interstrand ligand reaction occurs via a click-reaction between an azide of the upconversion probe and a DBCO-ssDNA-biotin probe present in the solution. As a result of this specific and selective reaction, biotin-functionalized upconversion nanoparticles are produced. After that, the biotin-functionalized upconversion nanoparticles are selectively captured on a streptavidin-coated surface, producing an upconversion emission intensity that is proportional to the target concentration present in the sample. The validity of the system was checked using samples containing total RNA extracted from mosquitoes or human serum samples that have been doped with a synthetic sequence that appears in the small subunit ribosomal RNA of the Plasmodium falciparum and which was used as a target model. The result of these experiments demonstrated an exceptionally low detection limit close to 1 × 10^–17 moles per well (100 fM). The simplicity and potential of the presented system could allow its use as a screening tool for multiple RNA or DNA sequence analyses.

2 Materials

Click to copy section linkSection link copied!

Methanol (99.9%), n-hexane (95%), N,N-dimethylformamide anhydrous (99.8%), tetraethyl orthosilicate (99.999%), polyoxyethylene (5) nonylphenylether branched (IGEPAL CO-520), ammonium hydroxide solution (30%), (3-aminopropyl)triethoxysilane (99%), succinic anhydride (99%), Bionic buffer 10× concentrated, HEPES 99.5%, NaCl BioXtra 99.5%, dimethyl sulfoxide 99.9%, N-(3-(dimethylamino)propyl)-N′-ethylcarbodiimide hydrochloride (99%), and N-hydroxysulfosuccinimide sodium salt (Sulfo-NHS) (98%) were purchased from Sigma-Aldrich and used as received. The modified DNA sequences NH₂-ssDNA-N₃ probes 1 and 2 were purchased from ATDBio. The target strands and the noncomplementary strands were acquired from Invitrogen. The mismatch strands were acquired from Integrated DNA Technologies. A complete description of the sequences is given in Table 1. Streptavidin-coated well-plates (UniverSA96) were purchased from Kaivogen (Turku, Finland).

Table 1. Oligonucleotide Sequences Used in This Work

name	sequence
probe 1	5′ NH₂-C(6)-TTTTT-TT-GTA-TAT-TTA-TA-N₃ 3′
probe 2	5′ DBCO-A-CAT-AGT-TGT-ACG-TTTTT-Bio-teg 3′
targets	*DNA 5′ CGT-ACA-ACT-ATG-TTA-TAA-ATA-TAC-AA 3′
targets	*RNA 5′ CGU-ACA-ACU-AUG-UUA-UAA-AUA-UAC-AA 3′
one mismatch (lateral)	5′ CGT-AAA-ACT-ATG-TTA-TAA-ATA-TAC-AA 3′
one mismatch (middle)	5′ CGT-ACA-ACT-ATG-TCA-TAA-ATA-TAC-AA 3′
three mismatches	5′ CGT-ACA-ACT-ATT-CCA-TAA-ATA-TAC-AA 3′
noncomplementary	5′ CAG-AAG-UCA-GGU-CGG-AUU-AAG-CC 3′

3 Characterization

Click to copy section linkSection link copied!

Transmission electron microscopy (TEM) analyses were carried out using a JEOL JEM 1010 operated at 80 kV coupled with a digital camera GATAN MegaView II. High-resolution TEM (HRTEM) studies were performed in a JEOL JEM 2100 operated at 200 kV with a digital camera GATAN CCD Orius SC1000. Z-potential experiments were carried out using a Malvern Nano-ZS. Thermogravimetric experiments were performed using a TGA/DSC-1 (Mettler-Toledo) working under an air atmosphere. The upconversion emission spectra were collected from the well-plate using a homemade system as depicted in Scheme 2C. The light beam from a 3 W CW laser (MDL-H-980-3W) working at 980 nm was transmitted through a 200 μm core fiber, which was coupled to a collimator lens. Then, the laser beam was reflected toward the well-plate using a short-pass dichroic mirror (Thorlabs DMSP950R) and focused on the sample using a 10× objective. The upconversion luminescence coming from the well-plate passed through the short-pass dichroic mirror and through a short-pass filter (Thorlabs FES900), which blocks the excitation wavelength. A collimator lens focused the light into an optical fiber that goes to the spectrometer Glacier X (B&W Tek).

4 Experimental Section

Click to copy section linkSection link copied!

The synthesis of the upconversion nanoparticles and their functionalization was carried out using sequential steps that are described in detail within the Supporting Information. Scheme 1 summarizes the chemical route followed to obtain the upconversion nanoparticles.

Scheme 1. Schematic Illustration of the Chemical Route for the Synthesis and Functionalization of NaYF₄:Yb,Er@SiO₂-DNA-N₃ Nanoparticles

5 Results and Discussion

Click to copy section linkSection link copied!

5.1 Particle Preparation, Characterization, and Functionalization

The synthesis of the fluorescent nanoparticles afforded monodisperse nanoparticles with a mean diameter of 36 ± 3 nm, as obtained from the TEM micrograph (see Figure 1A). X-ray energy dispersive spectroscopy analysis (Figure S1A) gave a composition of NaY_0.792F₄:Yb_0.189,Er_0.019 while the X-ray diffraction pattern of the particles (Figure S1B) demonstrated that they can be indexed to the hexagonal phase. In Figure 1B, one can observe a thin and homogeneous layer around each nanoparticle with a mean thickness of 7 nm, which was the result of the silica deposition reaction. Figure 1C,D depicts an HRTEM photograph of a NaYF₄:Yb,Er@SiO₂, nanoparticle, showing its crystalline structure in contrast with the amorphous silica shell. The silica layer confers hydrophilic behavior to the nanoparticles and permits their dispersion in aqueous media, as well as being a functional platform for their successive functionalization with ssDNA, as depicted in Scheme 1. A complete description of the nanoparticle functionalization and characterization is given in the Supporting Information. Figure S1C shows the upconversion luminescence spectrum of the NaYF₄:Yb,Er@SiO₂ nanoparticles under excitation with a 980 nm CW laser. We observed two green emission peaks near 525 and 545 nm due to the ²H_11/2 → ⁴I_15/2 and ⁴S_3/2 → ⁴I_15/2 transitions of the Er³⁺ ions, respectively. A red emission, with similar intensity, near 655 nm is also observed due to the ⁴F_9/2 → ⁴I_15/2 transition of the Er³⁺ ions.

Figure 1. TEM micrographs of the synthesized NaYF₄;Yb,Er nanoparticles (A) and NaYF₄;Yb,Er@SiO₂ nanoparticles (B). (C) HRTEM image of a NaYF₄;Yb,Er@SiO₂ nanoparticle. (D) Magnification of the image in (C). The scale bars in (A) and (B) are 50 nm, whereas in (C) and (D) they are 10 and 5 nm, respectively.

5.2 Well-Plate Signal Detection and Protocol Optimization

5.2.1 Interstrand Ligand Reaction

The sensor is based on a hybridization process that renders an interstrand ligand reaction between the NaYF₄;Yb,Er@SiO₂-ssDNA-N₃ strand (probe 1) and the DBCO-ssDNA-biotin strand (probe 2). This hybridization requires the presence of a target sequence, which acts as splint strand bringing the probes 1 and 2 closer, yielding the strain-promoted alkyne–azide cycloaddition (SPAAC) reaction, (31) as seen in Scheme 2. This process permits in a subsequent step the selective capture of the resulting NaYF₄;Yb,Er@SiO₂-dsDNA-biotin nanoparticles on a streptavidin-coated surface. To analyze the performance of the sensor, we computed the intensity of the upconversion emission by integrating the emission spectra around the red band between 640 and 680 nm.

Scheme 2. Schematic Illustration of the Action Mechanism of the Proposed Sensor^a

This strategy was designed to provide robustness to the sensor, because, in the absence of the click-reaction, any variation of the physicochemical properties of the media, like temperature or ionic strength, could revert the hybridization process, inducing the separation of probe 2 from probe 1, particularly when targets with low melting temperatures are involved in the hybridization. Therefore, the interstrand ligation stabilizes the incorporation of biotin moieties on the NaYF₄;Yb,Er@SiO₂-dsDNA nanoparticles and permits use of a stringent cleaning process to remove the physisorbed UCNPs without the risk of removing the selectively captured UCNPs. To highlight the relevance of the click-reaction process, we compared the photoluminescence obtained from a system designed to enable the interstrand ligand reaction with another system unable to yield such a reaction (see Figure 2). In both cases, we washed the solid support with different cleaning protocols.

Figure 2. Luminescence spectra obtained from NaYF₄;Yb,Er@SiO₂-ssDNA-N₃ and DBCO-ssDNA-biotin able to produce interstrand ligation (blue line) and NaYF₄;Yb,Er@SiO₂-ssDNA-N₃ and ssDNA-biotin, which are unable to produce interstrand ligation (red line), in the presence of 10^–13 moles per well (1 nM) of target sequence and after washing the solid support with 10 mM of HEPES buffer and different concentrations of NaCl at 50 °C: 150 mM in (A) and 50 mM in (B).

As one can observe from these experiments, there was a notable reduction of the photoluminescent intensity, when probes 1 and 2 were not able to yield the interstrand ligand reaction. This reduction could be attributed to a denaturalization of the double strands during the solid support cleaning process, which separates probes 1 and 2, washing away the UCNPs from the surface. When the interstrand ligand reaction takes place, probes 1 and 2 are still bound together after denaturalization and therefore remain attached on the well surface. Consequently, the NaYF₄;Yb,Er@SiO₂-dsDNA-biotin nanoparticles with inter-strand that have undergone the interstrand ligand reaction resist the cleaning steps with the buffer at 50 °C or with buffer with low ionic strength, which in principle could denaturalize the double strands constituted by the short oligonucleotides. Figure S2 depicts the results when the same experiments were carried out in the absence of target sequences. From these experiments we can observe that the background signals are basically the same and due to nonspecific physisorption.

5.2.2 Binding Kinetic Experiments

One of the parameters studied to optimize the signal of the sensor was the incubation time required by the streptavidin-coated well-plate to capture the maximum amount of biotin-functionalized nanoparticles. These experiments were performed by measuring the fluorescence signal for three independent samples with a fixed target amount of 10^–12 moles per well (10 nM) and comparing this signal with the one obtained from three blank samples. Figure 3 shows the luminescence signal collected from the streptavidin-coated surface after being incubated with 1 μg of UCNP@SiO₂-dsDNA-biotin produced by the hybridization of 10^–12 moles of the target and 2 × 10^–12 moles (20 nM) of probe 2. Figure 3A shows the increment of the luminescence signal as a function of time, reaching a plateau after 120 min. The time evolution of simple receptor–ligand interactions is usually described by a single exponential process with an observed rate constant k_obs that depends on the kinetic parameters, that is, the association (k_on) and dissociation (k_off) rate constants, and the ligand concentration (C), so that k_obs = k_off(C/K_d + 1). (32) By fitting our data to an exponential function, we obtained a value of the rate constant of k_obs = 3.8 × 10^–4 s^–1, which means that the half-time of the equilibrium reaction is nearly 30 min. Assuming an equilibrium dissociation constant of K_d = K_off/K_on = 10^–12 M, (33) and a ligand concentration of 10^–10 M, the calculated k_on and k_off values for our system would be 3 × 10⁶ M^–1 s^–1 and 3 × 10^–6 s^–1, respectively. These values are similar to the ones found in other works. (34)Figure 3A also shows the signal obtained from the blank samples (background signal), which increases linearly with time (red line). Therefore, specific and nonspecific interactions exhibit different kinetics, which must be taken into account to optimize the system. For this reason, we analyzed the time evolution of the signal to background ratio and the result is shown in Figure 3B. We can observe that the signal to background ratio reaches a maximum value of 15 after 120 min (see red line). However, the signal-to-noise ratio (S/N = average signal/standard deviation of the blank) obtained from the measurements also reaches a plateau with a value of 140 after 120 min, as depicted in Figure 3B (black line). As a result of these kinetic experiments, we decided to use an incubation time of 120 min for all experiments.

Figure 3. (A) Time evolution of the upconversion signal on the streptavidin-coated well-plate during the incubation process. The blue points correspond to the signal measured after incubating the biotin-functionalized UCNPs obtained from hybridization with 1 μg of probe 1 and 2 × 10^–12 moles of probe 2 with 10^–12 moles (10 nM) of target sequence per well. The red points represent the signal of the blank samples using the same procedure described before but without the target sequence. (B) Signal-to-background ratio (left axis) and signal-to-noise ratio (right axis) as a function of incubation time.

5.2.3 Sensor Calibration

Figure 4A shows the red upconversion emission spectra collected from the multiwell-plates for different concentrations of target sequence. Here, we can see that the intensity of the emission spectrum collected from the multiwell-plate gradually increases with the amount of complementary target sequence added during the hybridization step. This result indicates that the presence of higher amounts of target sequences yields more biotin-functionalized UCNPs that can be captured on the streptavidin-coated wells during the incubation process. We computed the intensity of the upconversion emission by integrating the emission spectra around the red peak. The result versus the target concentration is shown in Figure 4B in a log–log plot demonstrating the feasibility of our sensor. Each point of this graph was obtained averaging the luminescence intensity of 10 different positions at each well from three independent samples; the shown intensities are blank subtracted.

Figure 4. (A) Upconversion emission spectra collected from the multiwell-plate after being incubated with biotin-functionalized upconversion nanoparticles produced by hybridization with different amounts of target sequences. (B) Upconversion intensity collected from the multiwell-plate as a function of target concentration from 1 × 10^–18 to 1 × 10^–13 moles per well (10 fM to 1 nM). The signal intensity is blank subtracted. The error bars are the standard deviation obtained from measurements at 10 different positions on each well out of three independent samples for each target concentration. The blue dashed line indicates the LOD based on 3-fold SD of the blank samples.

As one can observe, the emission intensity collected from the well-plate roughly follows a straight line in the log–log plot of Figure 4B. From these data, we obtain the relative sensitivity changes with target concentration as S_r (%/moles per well) = 30/C_target, which means a relative sensitivity of 0.3%/attomoles per well for a target concentration of 10^–16 moles per well. The sensor shows high sensitivity and a large dynamic range, which spans over 4 orders of magnitude. Also, the blank value obtained was 950 counts/s nm with a standard deviation of 120 counts/s nm. This result defined the lowest target concentration (limit of detection, LOD) that the system can detect, which is close to 10^–17 moles per well (100 fM). The LOD was calculated as 3-fold the standard deviation of the blank value.

With the aim of evaluating the specificity of the sensor, we analyzed the fluorescence signal in the presence of different amounts of total RNA obtained from healthy mosquitoes but in the absence of target sequences. This experiment can give us an idea about the proportion of true negatives identified as such under different amounts of total RNA. The results are presented in Figure 5A. Here, one can observe that independent of the amount of total RNA, the signal of the sensor is constant with an average value of 830 ± 102 counts/s nm, which is close to the background obtained in the absence of total RNA (950 ± 120 counts/s nm). This result demonstrates that in the presence of noncomplementary sequences, the sensor gives a signal similar to the negative control.

Figure 5. A) Upconversion emission obtained from blank samples prepared in the presence of different amounts of total RNA from healthy mosquitoes and in the absence of target sequences. The red line indicates the average value 830 counts/s nm. (B) Upconversion emission obtained after hybridizing 1 μg of upconversion nanoparticles with 10^–12 moles per well of different sequences: full complementary sequences (Target), a sequence containing a single mismatch in the middle (MS1), a sequence containing three mismatches in the middle (MS2), a sequence containing a single mismatch in the first quarter of the strand (MS3), noncomplementary sequences (NCS), and in the absence of target sequences (BCK). The error bars indicate the standard deviation obtained from the experiments. (C) Upconversion intensity obtained after spiking samples containing 100 ng of total RNA with varying concentrations of target sequences. (D) Upconversion intensity obtained after spiking samples containing human serum with varying concentrations of target sequences. The intensities in (C) and (D) were blank subtracted and the blue dashed line indicates the threshold resulting from three times the standard deviation of the control signal. In all graphs, the error bars indicate the standard deviation.

In addition, the capacity of the sensor to discriminate between target sequences and mismatched sequences was also studied. Figure 5B represents the upconversion emission obtained after hybridizing 1 μg of upconversion nanoparticles in the presence of 2 × 10^–12 moles per well of biotin-functionalized probe 2 with 10^–12 moles per well of different sequences: full complementary target sequences (Target), a sequence containing a single mismatch in the middle of the strand (MS1), a sequence containing three mismatches in the middle of the strand (MS2), a sequence containing a single mismatch in the first quarter of the strand (MS3), noncomplementary sequences, and in the absence of target sequences (BCK). Scheme 3 illustrates the different mismatch sequences used in this experiment.

Scheme 3. Graphical Representation of the Possible Duplexes Formed^a

These experiments show that when the particles were hybridized with sequences that have a single mismatch placed on the center of the strand (MS1), the sensor signal decreases slightly with respect to the signal obtained with full complementary targets (see Figure 5B). This small reduction of the signal intensity could be attributed to the small hampering that this single mismatch introduces in the 3′ end of probe 1. In contrast, when the particles were hybridized with a sequence that has three mismatches located on the center of the strands (MS2), the signal decreased conspicuously due to the hybridization hindrance that under this scenario affects the 3′ and 5′ ends of probes 1 and 2, respectively. Finally, when the sensor was tested against a sequence that has a single mismatch that affected its hybridization with the central part of probe 2 (MS3), the signal obtained by the sensor was similar to those obtained with the noncomplementary sequences and blank, indicating that this mutation could completely hamper the incorporation of the biotin moiety on the surface of the UCNP, which is the base of the sensor. These results demonstrate that the proposed sensor exhibits a selectivity that is dependent on the position of the mismatch.

Furthermore, the analytical properties of the system were studied by analyzing samples containing 100 ng of total RNA spiked with different amounts of target strands. As expected, we observed an increment of upconversion emission when the concentration of the target sequence was increased (see log–log curve of Figure 5C). In this case, the relative sensitivity is slightly lower with Sr of 20/C_target%/moles per well, which means a sensitivity of 0.2%/attomoles per well for a target concentration of 10^–16 moles per well. The small variation in the sensitivity of the sensor could be related to the high amount of total RNA added in the sample that somehow hampers the hybridization process, reducing the number of biotin-functionalized UCNPs. Nevertheless, under this condition, the sensor can detect the presence of small oligonucleotides with a LOD close to 10^–17 moles per well (100 fM).

Finally, we studied the analytical properties of our sensor in the presence of human serum. For that, different serum samples obtained from humans were spiked with varying amounts of target containing small oligonucleotides and were analyzed without sample pretreatment. The result of these experiments is shown in Figure 5D. Here, one can observe that the system was able to detect the small oligonucleotides in the serum samples, with a LOD of around 10^–17 moles per well, showing the capacity of the proposed sensor to work with raw samples, facilitating the measurement and reducing the cost that would involve the use of RNA extraction kits.

All of these results reveal that the detection limit of the proposed sensor is in the range of 10 attomoles per well (100 fM), indicating the potential of the proposed sensor to detect extremely low amounts of target sequences. This LOD is significantly smaller than the one found in other sensors based on the solid phase, which are summarized in Table 2.

Table 2. Comparison of the Sensor LOD for Different Techniques

sensor methodology^a	linear range	LOD	reference
FRET	30 fmol to 30 pmol	30 fmol	34
EIS	1 pM to 500 nM	0.5 pM	35
SERS	10 pM to 10 nM	10 pM	36
ELC	50 pM to 10 nM	10 pM	37
PLGA	100 pM to 1 nM	100 pM	38
SCUP	100 fM to 10 nM	100 fM	this work

FRET, fluorescence resonant energy transfer; EIS, electrochemical impedance spectroscopy; SERS, surface enhancement Raman spectroscopy; ELC, electrochemical redox detection; PLGA; photoluminescence graphene assay; SCUP, selective capture of upconversion nanoparticles.

6 Conclusions

Click to copy section linkSection link copied!

In this work, we have synthesized upconversion nanoparticles conveniently functionalized with ssDNA strands to create a sensor able to detect the presence of specific target sequences on a solid support. The LOD of the proposed sensor was around 10^–17 moles per well and the relative sensitivity at this target concentration was around 0.3%/attomoles per well. The signal produced by the sensor upon hybridization with sequences that have mismatches or noncomplementary sequences was significantly smaller than the one obtained for the full complementary sequence at the same concentration. Finally, spiked-in samples were prepared by adding different amounts of a synthetic target sequence in samples containing 100 ng of total RNA extracted from healthy mosquitoes or human serum samples. The results of these experiments demonstrate the capacity of the sensor to detect the target sequence with high selectivity and sensitivity. In addition, its capacity to directly detect the target sequence in serum samples demonstrates its suitability to be used as a low cost point-of-care diagnostic, as the use of RNA extraction kits or sample pretreatment are not necessary.

Supporting Information

Click to copy section linkSection link copied!

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsami.7b00575.

Materials, synthesis, characterization and detection method (PDF)

am7b00575_si_001.pdf (758.97 kb)

Terms & Conditions

Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

Author Information

Click to copy section linkSection link copied!

Corresponding Authors
- Sonia Melle - Faculty of Optics and Optometry, Complutense University of Madrid, Arcos de Jalón 118, 28037 Madrid, Spain; Email: [email protected]
- Jorge Rubio-Retama - Department of Physical Chemistry II, Faculty of Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain; http://orcid.org/0000-0002-1785-5844; Email: [email protected]
Authors
- Diego Mendez-Gonzalez - Department of Physical Chemistry II, Faculty of Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain
- Marco Laurenti - Department of Physical Chemistry II, Faculty of Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain
- Alfonso Latorre - Nanobiotecnología (IMDEA-Nanociencia), Unidad Asociada al Centro Nacional de Biotecnología (CSIC), 28049 Madrid, Spain
- Alvaro Somoza - Nanobiotecnología (IMDEA-Nanociencia), Unidad Asociada al Centro Nacional de Biotecnología (CSIC), 28049 Madrid, Spain; http://orcid.org/0000-0001-9873-435X
- Ana Vazquez - Laboratorio de Arbovirus, Centro Nacional de Microbiología-Instituto de Salud Carlos III, Majadahonda, 28220 Madrid, Spain
- Ana Isabel Negredo - Laboratorio de Arbovirus, Centro Nacional de Microbiología-Instituto de Salud Carlos III, Majadahonda, 28220 Madrid, Spain
- Enrique López-Cabarcos - Department of Physical Chemistry II, Faculty of Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain
- Oscar G. Calderón - Faculty of Optics and Optometry, Complutense University of Madrid, Arcos de Jalón 118, 28037 Madrid, Spain
Notes
The authors declare no competing financial interest.

Acknowledgment

Click to copy section linkSection link copied!

The authors are grateful for the financial support from the Bill & Melinda Gates Foundation, with Grant OPP1128411, Asociación Española Contra el Cáncer, Santander-Universidad Complutense project PR26/16-12B-3, and from the Spanish MINECO for the projects MAT2014-55065-R, SAF2014-56763-R, and FIS2013-41709-P.

References

Click to copy section linkSection link copied!

This article references 38 other publications.

1
Fire, A.; Xu, S.; Montgomery, M. K.; Kostas, S. A.; Driver, S. E.; Mello, C. C. Potent and Specific Genetic Interference by Double-Stranded RNA in Caenorhabditis elegans Nature 1998, 391, 806– 811 DOI: 10.1038/35888
Google Scholar
1
Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans
Fire, Andrew; Xu, SiQun; Montgomery, Mary K.; Kostas, Steven A.; Driver, Samuel E.; Mello, Craig C.
Nature (London) (1998), 391 (6669), 806-811CODEN: NATUAS; ISSN:0028-0836. (Macmillan Magazines)
Exptl. introduction of RNA into cells can be used in certain biol. systems to interfere with the function of an endogenous gene. Such effects have been proposed to result from a simple antisense mechanism that depends on hybridization between the injected RNA and endogenous mRNA transcripts. RNA interference has been used in the nematode C. elegans to manipulate gene expression. Here we investigate the requirements for structure and delivery of the interfering RNA. To our surprise, we found that double-stranded RNA was substantially more effective at producing interference than was either strand individually. After injection into adult animals, purified single strands had at most a modest effect, whereas double-stranded mixts. caused potent and specific interference. The effects of this interference were evident in both the injected animals and their progeny. Only a few mols. of injected double-stranded RNA were required per affected cell, arguing against stoichiometric interference with endogenous mRNA and suggesting that there could be a catalytic or amplification component in the interference process.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK1cXhtlCju74%253D&md5=7bd291ca75d455bbbe1dee41c3362208
2
Hess, A. M.; Prasad, A. N.; Ptitsyn, A.; Ebel, G. D.; Olson, K. E.; Barbacioru, C.; Monighetti, C.; Campbell, C. L. Small RNA Profiling of Dengue Virus-Mosquito Interactions Implicates the PIWI RNA Pathway in Anti-Viral Defense BMC Microbiol. 2011, 11, 45 DOI: 10.1186/1471-2180-11-45
Google Scholar
2
Small RNA profiling of Dengue virus-mosquito interactions implicates the PIWI RNA pathway in anti-viral defense
Hess, Ann M.; Prasad, Abhishek N.; Ptitsyn, Andrey; Ebel, Gregory D.; Olson, Ken E.; Barbacioru, Catalin; Monighetti, Cinna; Campbell, Corey L.
BMC Microbiology (2011), 11 (), 45CODEN: BMMIBC; ISSN:1471-2180. (BioMed Central Ltd.)
Background: Small RNA (sRNA) regulatory pathways (SRRPs) are important to anti-viral defense in mosquitoes. To identify crit. features of the virus infection process in Dengue serotype 2 (DENV2)-infected Ae. aegypti, the authors deep-sequenced small non-coding RNAs. Triplicate biol. replicates were used so that rigorous statistical metrics could be applied. Results: In addn. to virus-derived siRNAs (20-23nts) previously reported for other arbovirus-infected mosquitoes, PIWI pathway sRNAs (piRNAs) (24-30nts) and unusually small RNAs (usRNAs) (13-19nts) were produced in DENV-infected mosquitoes. A major catalytic enzyme of the siRNA pathway, Argonaute 2 (Ago2), co-migrates with a 1 megadalton complex in adults prior to bloodfeeding. SRNAs were cloned and sequenced from Ago2 immunopptns. Viral sRNA patterns change over infection. Host sRNAs were mapped to the published aedine transcriptome and subjected to anal. using edgeR (Bioconductor). SRNA profiles are altered early in DENV2 infection, and mRNA targets from mitochondrial, transcription/translation, and transport functional categories are affected. Moreover, small non-coding RNAs (ncRNAs), such as tRNAs, spliceosomal U RNAs, and snoRNAs are highly enriched in DENV-infected samples at 2 and 4 dpi. Conclusions: These data implicate the PIWI pathway in anti-viral defense. Changes to host sRNA profiles indicate that specific cellular processes are affected during DENV infection, such as mitochondrial function and ncRNA levels. Together, these data provide important progress in understanding the DENV2 infection process in Ae. aegypti.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXjt1Khtbo%253D&md5=3e63ac4e618509bb0a3b14f61690a157
3
Lopez, J. P.; Diallo, A.; Cruceanu, C.; Fiori, L. M.; Laboissiere, S.; Guillet, I.; Fontaine, J.; Ragoussis, J.; Benes, V.; Turecki, G.; Ernst, C. Biomarker Discovery: Quantification of microRNAs and Other Small Non-Coding RNAs Using next Generation Sequencing BMC Med. Genomics 2015, 8, 35 DOI: 10.1186/s12920-015-0109-x
Google Scholar
3
Biomarker discovery: quantification of microRNAs and other small non-coding RNAs using next generation sequencing
Lopez Juan Pablo; Diallo Alpha; Cruceanu Cristiana; Fiori Laura M; Turecki Gustavo; Ernst Carl; Lopez Juan Pablo; Cruceanu Cristiana; Ragoussis Jiannis; Turecki Gustavo; Ernst Carl; Laboissiere Sylvie; Guillet Isabelle; Fontaine Joelle; Ragoussis Jiannis; Benes Vladimir
BMC medical genomics (2015), 8 (), 35 ISSN:.
BACKGROUND: Small ncRNAs (sncRNAs) offer great hope as biomarkers of disease and response to treatment. This has been highlighted in the context of several medical conditions such as cancer, liver disease, cardiovascular disease, and central nervous system disorders, among many others. Here we assessed several steps involved in the development of an ncRNA biomarker discovery pipeline, ranging from sample preparation to bioinformatic processing of small RNA sequencing data. METHODS: A total of 45 biological samples were included in the present study. All libraries were prepared using the Illumina TruSeq Small RNA protocol and sequenced using the HiSeq2500 or MiSeq Illumina sequencers. Small RNA sequencing data was validated using qRT-PCR. At each stage, we evaluated the pros and cons of different techniques that may be suitable for different experimental designs. Evaluation methods included quality of data output in relation to hands-on laboratory time, cost, and efficiency of processing. RESULTS: Our results show that good quality sequencing libraries can be prepared from small amounts of total RNA and that varying degradation levels in the samples do not have a significant effect on the overall quantification of sncRNAs via NGS. In addition, we describe the strengths and limitations of three commercially available library preparation methods: (1) Novex TBE PAGE gel; (2) Pippin Prep automated gel system; and (3) AMPure XP beads. We describe our bioinformatics pipeline, provide recommendations for sequencing coverage, and describe in detail the expression and distribution of all sncRNAs in four human tissues: whole-blood, brain, heart and liver. CONCLUSIONS: Ultimately this study provides tools and outcome metrics that will aid researchers and clinicians in choosing an appropriate and effective high-throughput sequencing quantification method for various study designs, and overall generating valuable information that can contribute to our understanding of small ncRNAs as potential biomarkers and mediators of biological functions and disease.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2MbptFCitA%253D%253D&md5=8daa76441523d6c5a5237aefa64cdc13
4
Gilad, S.; Meiri, E.; Yogev, Y.; Benjamin, S.; Lebanony, D.; Yerushalmi, N.; Kushnir, M.; Cholakh, H.; Melamed, N.; Bentwich, Z.; Hod, M.; Goren, Y.; Chajut, A. Serum MicroRNAs Are Promising Novel Biomarkers PLoS One 2008, 3e3148 DOI: 10.1371/journal.pone.0003148
Google Scholar
There is no corresponding record for this reference.
5
Calin, G. A.; Croce, C. M. MicroRNA Signatures in Human Cancers Nat. Rev. Cancer 2006, 6, 857– 866 DOI: 10.1038/nrc1997
Google Scholar
5
MicroRNA signatures in human cancers
Calin, George A.; Croce, Carlo M.
Nature Reviews Cancer (2006), 6 (11), 857-866CODEN: NRCAC4; ISSN:1474-175X. (Nature Publishing Group)
A review. MicroRNA (miRNA) alterations are involved in the initiation and progression of human cancer. The causes of the widespread differential expression of miRNA genes in malignant compared with normal cells can be explained by the location of these genes in cancer-assocd. genomic regions, by epigenetic mechanisms and by alterations in the miRNA processing machinery. MiRNA-expression profiling of human tumors has identified signatures assocd. with diagnosis, staging, progression, prognosis and response to treatment. In addn., profiling has been exploited to identify miRNA genes that might represent downstream targets of activated oncogenic pathways, or that target protein-coding genes involved in cancer.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XhtFWhs7fM&md5=3e20b58432ef9509e227fb1396e0ee15
6
Flemming, A. Targeting miRNA Pathology in Heart Disease Nat. Rev. Drug Discovery 2014, 13, 336 DOI: 10.1038/nrd4311
Google Scholar
There is no corresponding record for this reference.
7
Munshi, S. U.; Panda, H.; Holla, P.; Rewari, B. B.; Jameel, S. MicroRNA-150 Is a Potential Biomarker of HIV/AIDS Disease Progression and Therapy PLoS One 2014, 9e95920 DOI: 10.1371/journal.pone.0095920
Google Scholar
There is no corresponding record for this reference.
8
Liang, H.; Zhou, Z.; Zhang, S.; Zen, K.; Chen, X.; Zhang, C. Identification of Ebola Virus microRNAs and Their Putative Pathological Function Sci. China: Life Sci. 2014, 57, 973– 981 DOI: 10.1007/s11427-014-4759-2
Google Scholar
8
Identification of Ebola virus microRNAs and their putative pathological function
Liang, HongWei; Zhou, Zhen; Zhang, SuYang; Zen, Ke; Chen, Xi; Zhang, ChenYu
Science China: Life Sciences (2014), 57 (10), 973-981CODEN: SCLSCJ; ISSN:1674-7305. (Science China Press)
Ebola virus (EBOV), a member of the filovirus family, is an enveloped neg.-sense RNA virus that causes lethal infections in humans and primates. Recently, >1000 people have been killed by the Ebola virus disease in Africa, yet no specific treatment or diagnostic tests for EBOV are available. The authors identified two putative viral microRNA precursors (pre-miRNAs) and three putative mature microRNAs (miRNAs) derived from the EBOV genome. The prodn. of the EBOV miRNAs was further validated in HEK293T cells transfected with a pcDNA6.2-GW/EmGFP-EBOV-pre-miRNA plasmid, indicating that EBOV miRNAs can be produced through the cellular miRNA processing machinery. The authors also predicted the potential target genes of these EBOV miRNAs and their possible biol. functions. Overall, this study reports for the first time that EBOV may produce miRNAs, which could serve as non-invasive biomarkers for the diagnosis and prognosis of EBOV infection and as therapeutic targets for Ebola viral infection treatment.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhslSrsbnL&md5=19032eb8699c8371efc2351fd7092197
9
Hong, Y.; Wang, C.; Fu, Z.; Liang, H.; Zhang, S.; Lu, M.; Sun, W.; Ye, C.; Zhang, C. Y.; Zen, K.; Shi, L.; Zhang, C.; Chen, X. Systematic Characterization of Seminal Plasma piRNAs as Molecular Biomarkers for Male Infertility Sci. Rep. 2016, 624229 DOI: 10.1038/srep24229
Google Scholar
9
Systematic characterization of seminal plasma piRNAs as molecular biomarkers for male infertility
Hong, Yeting; Wang, Cheng; Fu, Zheng; Liang, Hongwei; Zhang, Suyang; Lu, Meiling; Sun, Wu; Ye, Chao; Zhang, Chen-Yu; Zen, Ke; Shi, Liang; Zhang, Chunni; Chen, Xi
Scientific Reports (2016), 6 (), 24229CODEN: SRCEC3; ISSN:2045-2322. (Nature Publishing Group)
Although piwi-interacting RNAs (piRNAs) play pivotal roles in spermatogenesis, little is known about piRNAs in the seminal plasma of infertile males. In this study, we systematically investigated the profiles of seminal plasma piRNAs in infertile males to identify piRNAs that are altered during infertility and evaluate their diagnostic value. Seminal plasma samples were obtained from 211 infertile patients (asthenozoospermia and azoospermia) and 91 fertile controls. High-throughput sequencing technol. was employed to screen piRNA profiles in seminal plasma samples pooled from healthy controls and infertile patients. The results identified 61 markedly altered piRNAs in infertile patient groups compared with control group. Next, a quant. RT-PCR assay was conducted in the training and validation sets to measure and confirm the concns. of altered piRNAs. The results identified a panel of 5 piRNAs that were significantly decreased in seminal plasma of infertile patients compared with healthy controls. ROC curve anal. and risk score anal. revealed that the diagnostic potential of these 5 piRNAs to distinguish asthenozoospermic and azoospermic individuals from healthy controls was high. In summary, this study identifies a panel of piRNAs that can accurately distinguish fertile from infertile males. This finding may provide pathophysiol. clues about the development of infertility.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XmtVKju7s%253D&md5=aafa4784167ba4ef48b4b0024a5770de
10
Morazzani, E. M.; Wiley, M. R.; Murreddu, M. G.; Adelman, Z. N.; Myles, K. M. Production of Virus-Derived Ping-Pong-Dependent piRNA-like Small RNAs in the Mosquito Soma PLoS Pathog. 2012, 8e1002470 DOI: 10.1371/journal.ppat.1002470
Google Scholar
There is no corresponding record for this reference.
11
Alonso-Cristobal, P.; Vilela, P.; El-Sagheer, A.; Lopez-Cabarcos, E.; Brown, T.; Muskens, O. L.; Rubio-Retama, J.; Kanaras, A. G. Highly Sensitive DNA Sensor Based on Upconversion Nanoparticles and Graphene Oxide ACS Appl. Mater. Interfaces 2015, 7, 12422– 12429 DOI: 10.1021/am507591u
Google Scholar
11
Highly Sensitive DNA Sensor Based on Upconversion Nanoparticles and Graphene Oxide
Alonso-Cristobal, P.; Vilela, P.; El-Sagheer, A.; Lopez-Cabarcos, E.; Brown, T.; Muskens, O. L.; Rubio-Retama, J.; Kanaras, A. G.
ACS Applied Materials & Interfaces (2015), 7 (23), 12422-12429CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)
In this work we demonstrate a DNA biosensor based on fluorescence resonance energy transfer (FRET) between NaYF4:Yb,Er nanoparticles and graphene oxide (GO). Monodisperse NaYF4:Yb,Er nanoparticles with a mean diam. of 29.1 ± 2.2 nm were synthesized and coated with a SiO2 shell of 11 nm, which allowed the attachment of single strands of DNA. When these DNA-functionalized NaYF4:Yb,Er@SiO2 nanoparticles were in the proximity of the GO surface, the π-π stacking interaction between the nucleobases of the DNA and the sp2 carbons of the GO induced a FRET fluorescence quenching due to the overlap of the fluorescence emission of the NaYF4:Yb,Er@SiO2 and the absorption spectrum of GO. By contrast, in the presence of the complementary DNA strands, the hybridization leads to double-stranded DNA that does not interact with the GO surface, and thus the NaYF4:Yb,Er@SiO2 nanoparticles remain unquenched and fluorescent. The high sensitivity and specificity of this sensor introduces a new method for the detection of DNA with a detection limit of 5 pM.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsF2ht7w%253D&md5=d4dc92c0e83a786d31ddeadaf28495ac
12
Laurenti, M.; Paez-Perez, M.; Algarra, M.; Alonso-Cristobal, P.; Lopez-Cabarcos, E.; Mendez-Gonzalez, D.; Rubio-Retama, J. Enhancement of the Upconversion Emission by Visible-to-Near-Infrared Fluorescent Graphene Quantum Dots for miRNA Detection ACS Appl. Mater. Interfaces 2016, 8, 12644– 12651 DOI: 10.1021/acsami.6b02361
Google Scholar
12
Enhancement of the Upconversion Emission by Visible-to-Near-Infrared Fluorescent Graphene Quantum Dots for miRNA Detection
Laurenti, Marco; Paez-Perez, Miguel; Algarra, Manuel; Alonso-Cristobal, Paulino; Lopez-Cabarcos, Enrique; Mendez-Gonzalez, Diego; Rubio-Retama, Jorge
ACS Applied Materials & Interfaces (2016), 8 (20), 12644-12651CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)
We developed a sensor for the detection of specific microRNA (miRNA) sequences that was based on graphene quantum dots (GQDs) and ssDNA-UCNP@SiO2. The proposed sensor exploits the interaction between the sp2 carbon atoms of the GQD, mainly π-π stacking, and the DNA nucleobases anchored on the upconversion nanoparticles (UCNPs). This interaction brings the GQD to the surface of the ssDNA-UCNP@SiO2 system, enhancing the upconversion emission. On the other hand, hybridization of the single-stranded DNA (ssDNA) chains anchored on the nanoparticles with their complementary miRNA sequences blocks the capacity of the UCNPs to interact with the GQD through π-π stacking. That gives as result a redn. of the fluorescent enhancement, which is dependent on the concn. of miRNA sequences. This effect was used to create a sensor for miRNA sequences with a detection limit of 10 fM.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XnsVWitbs%253D&md5=440d7d6c6e331bac6a7bd2365d2de75d
13
Yang, X.; Yu, Y.; Gao, Z. A Highly Sensitive Plasmonic DNA Assay Based on Triangular Silver Nanoprism Etching ACS Nano 2014, 8, 4902– 4907 DOI: 10.1021/nn5008786
Google Scholar
13
A Highly Sensitive Plasmonic DNA Assay Based on Triangular Silver Nanoprism Etching
Yang, Xinjian; Yu, Yuebo; Gao, Zhiqiang
ACS Nano (2014), 8 (5), 4902-4907CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)
Specific nucleic acid detection by using simple and low-cost assays is important in clin. diagnostics, mutation detection, and biodefense applications. Most current methods for the quantification of low concns. of DNA require costly and sophisticated instruments. Here, the authors have developed a facile DNA detection platform based on a plasmonic triangular silver nanoprism etching process, in which the shape and size of the nanoprisms were altered accompanied by a substantial surface plasmon resonance shift. Through the combination of enzyme-linked hybridization chain reaction amplification and inherent sensitivity of plasmonic silver nanoprisms, this assay could detect as low as 6.0 fM target DNA. Considering the high sensitivity and selectivity of this plasmonic DNA assay, it is expected to be of great interest in clin. diagnostics.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXmvFCjurc%253D&md5=a850a5eaf83c924d47304b5ba2bfb124
14
Tang, L.; Chun, I. S.; Wang, Z.; Li, J.; Li, X.; Lu, Y. DNA Detection Using Plasmonic Enhanced near-Infrared Photoluminescence of Gallium Arsenide Anal. Chem. 2013, 85, 9522– 9527 DOI: 10.1021/ac401169c
Google Scholar
14
DNA Detection Using Plasmonic Enhanced Near-Infrared Photoluminescence of Gallium Arsenide
Tang, Longhua; Chun, Ik Su; Wang, Zidong; Li, Jinghong; Li, Xiuling; Lu, Yi
Analytical Chemistry (Washington, DC, United States) (2013), 85 (20), 9522-9527CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)
Efficient near-IR detection of specific DNA with single nucleotide polymorphism selectivity is important for diagnostics and biomedical research. Herein, we report the use of gallium arsenide (GaAs) as a sensing platform for probing DNA immobilization and targeting DNA hybridization, resulting in ∼8-fold enhanced GaAs photoluminescence (PL) at ∼875 nm. The new signal amplification strategy, further coupled with the plasmonic effect of Au nanoparticles, is capable of detecting DNA mols. with a detection limit of 0.8 pM and selectivity against single base mismatches. Such an ultrasensitive near-IR sensor can find a wide range of biochem. and biomedical applications.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtlKktL3I&md5=e148ba21c812ac08bcff44370080f5f1
15
Tsang, M.-K.; Ye, W.; Wang, G.; Li, J.; Yang, M.; Hao, J. Ultrasensitive Detection of Ebola Virus Oligonucleotide Based on Upconversion Nanoprobe/Nanoporous Membrane System ACS Nano 2016, 10, 598– 605 DOI: 10.1021/acsnano.5b05622
Google Scholar
15
Ultrasensitive Detection of Ebola Virus Oligonucleotide Based on Upconversion Nanoprobe/Nanoporous Membrane System
Tsang, Ming-Kiu; Ye, WeiWei; Wang, Guojing; Li, Jingming; Yang, Mo; Hao, Jianhua
ACS Nano (2016), 10 (1), 598-605CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)
Ebola outbreaks are currently of great concern, and therefore, development of effective diagnosis methods is urgently needed. The key for lethal virus detection is high sensitivity, since early-stage detection of virus may increase the probability of survival. Here, we propose a luminescence scheme of assay consisting of BaGdF5:Yb/Er upconversion nanoparticles (UCNPs) conjugated with oligonucleotide probe and gold nanoparticles (AuNPs) linked with target Ebola virus oligonucleotide. As a proof of concept, a homogeneous assay was fabricated and tested, yielding a detection limit at picomolar level. The luminescence resonance energy transfer is ascribed to the spectral overlapping of upconversion luminescence and the absorption characteristics of AuNPs. Moreover, we anchored the UCNPs and AuNPs on a nanoporous alumina (NAAO) membrane to form a heterogeneous assay. Importantly, the detection limit was greatly improved, exhibiting a remarkable value at the femtomolar level. The enhancement is attributed to the increased light-matter interaction throughout the nanopore walls of the NAAO membrane. The specificity test suggested that the nanoprobes were specific to Ebola virus oligonucleotides. The strategy combining UCNPs, AuNPs, and NAAO membrane provides new insight into low-cost, rapid, and ultrasensitive detection of different diseases. Furthermore, we explored the feasibility of clin. application by using inactivated Ebola virus samples. The detection results showed great potential of our heterogeneous design for practical application.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtlSktw%253D%253D&md5=4d7221463dd314bbf3c1a937c1449c88
16
Chen, Z.; Chen, H.; Hu, H.; Yu, M.; Li, F.; Zhang, Q.; Zhou, Z.; Yi, T.; Huang, C. Versatile Synthesis Strategy for Carboxylic Acid-Functionalized Upconverting Nanophosphors as Biological Labels J. Am. Chem. Soc. 2008, 130, 3023– 3029 DOI: 10.1021/ja076151k
Google Scholar
16
Versatile Synthesis Strategy for Carboxylic Acid-functionalized Upconverting Nanophosphors as Biological Labels
Chen, Zhigang; Chen, Huili; Hu, He; Yu, Mengxiao; Li, Fuyou; Zhang, Qiang; Zhou, Zhiguo; Yi, Tao; Huang, Chunhui
Journal of the American Chemical Society (2008), 130 (10), 3023-3029CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
Up-converting rare-earth nanophosphors (UCNPs) have great potential to revolutionize biol. luminescent labels, but their use has been limited by difficulties in obtaining UCNPs that are biocompatible. To address this problem, the authors have developed a simple and versatile strategy for converting hydrophobic UCNPs into water-sol. and carboxylic acid-functionalized analogs by directly oxidizing oleic acid ligands with the Lemieux-von Rudloff reagent. This oxidn. process has no obvious adverse effects on the morphologies, phases, compns. and luminescent capabilities of UCNPs. Furthermore, as revealed by Fourier transform IR (FTIR) and NMR results, oleic acid ligands on the surface of UCNPs can be oxidized into azelaic acids (HOOC(CH2)7COOH), which results in the generation of free carboxylic acid groups on the surface. The presence of free carboxylic acid groups not only confers high soly. in water, but also allows further conjugation with biomols. such as streptavidin. A highly sensitive DNA sensor based on such streptavidin-coupled UCNPs have been prepd., and the demonstrated results suggest that these biocompatible UCNPs have great superiority as luminescent labeling materials for biol. applications.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXitVamt7w%253D&md5=882ec4da9fa107bff39cf7f4939c22ea
17
Ma, W.; Kuang, H.; Xu, L.; Ding, L.; Xu, C.; Wang, L.; Kotov, N. A. Attomolar DNA Detection with Chiral Nanorod Assemblies Nat. Commun. 2013, 42689 DOI: 10.1038/ncomms3689
Google Scholar
17
Attomolar DNA detection with chiral nanorod assemblies
Ma Wei; Kuang Hua; Xu Liguang; Ding Li; Xu Chuanlai; Wang Libing; Kotov Nicholas A
Nature communications (2013), 4 (), 2689 ISSN:.
Nanoscale plasmonic assemblies display exceptionally strong chiral optical activity. So far, their structural design was primarily driven by challenges related to metamaterials whose practical applications are remote. Here we demonstrate that gold nanorods assembled by the polymerase chain reaction into DNA-bridged chiral systems have promising analytical applications. The chiroplasmonic activity of side-by-side assembled patterns is attributed to a 7-9 degree twist between the nanorod axes. This results in a strong polarization rotation that matches theoretical expectations. The amplitude of the bisignate 'wave' in the circular dichroism spectra of side-by-side assemblies demonstrates excellent linearity with the amount of target DNA. The limit of detection for DNA using side-by-side assemblies is as low as 3.7 aM. This chiroplasmonic method may be particularly useful for biological analytes larger than 2-5 nm which are difficult to detect by methods based on plasmon coupling and 'hot spots'. Circular polarization increases for inter-nanorod gaps between 2 and 20 nm when plasmonic coupling rapidly decreases. Reaching the attomolar limit of detection for simple and reliable bioanalysis of oligonucleotides may have a crucial role in DNA biomarker detection for early diagnostics of different diseases, forensics and environmental monitoring.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2c7gt1Smsg%253D%253D&md5=1d0e5d950288b44286c90ae70a182060
18
Li, S.; Xu, L.; Ma, W.; Wu, X.; Sun, M.; Kuang, H.; Wang, L.; Kotov, N. A.; Xu, C. Dual-Mode Ultrasensitive Quantification of MicroRNA in Living Cells by Chiroplasmonic Nanopyramids Self-Assembled from Gold and Upconversion Nanoparticles J. Am. Chem. Soc. 2016, 138, 306– 312 DOI: 10.1021/jacs.5b10309
Google Scholar
18
Dual-mode ultrasensitive quantification of microRNA in living cells by chiroplasmonic nanopyramids self-assembled from gold and upconversion nanoparticles
Li, Si; Xu, Liguang; Ma, Wei; Wu, Xiaoling; Sun, Maozhong; Kuang, Hua; Wang, Libing; Kotov, Nicholas A.; Xu, Chuanlai
Journal of the American Chemical Society (2016), 138 (1), 306-312CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
Chiral self-assembled nanomaterials with biol. applications have attracted great interest. In this study, DNA-driven gold-upconversion nanoparticle (Au-UCNP) pyramids were fabricated to detect intracellular microRNA (miRNA) in real time. The Au-UCNP pyramids are doubly optically active, displaying strong plasmonic CD at 521 nm and significant luminescence in 500-600 nm, and therefore can be monitored by both of them. CD will decrease while the luminescence intensity increases in the presence of miRNA. The exptl. results show that the CD intensity had an outstanding linear range from 0.073 to 43.65 fmol/10 μgRNA and a limit of detection (LOD) of 0.03 fmol/10 μgRNA, whereas the luminescence intensity ranged from 0.16 to 43.65 fmol/10 μgRNA with a LOD of 0.12 fmol/10 μgRNA. These data indicate that the CD signal is much more sensitive to the concn. of miRNA than the luminescent signal, which is attributed to the strong CD intensity arising from the spin angular momentum of the photon interaction with chiral nanostructures and the plasmonic enhancement of the intrinsic chirality of DNA mols. in the pyramids. This approach opens up a new avenue to the ultrasensitive detection and quantification of miRNA in living cells.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXitVGrsr7F&md5=e389f8dfe701386660fff8d81b3e6537
19
Wang, F.; Liu, X. Recent Advances in the Chemistry of Lanthanide-Doped Upconversion Nanocrystals Chem. Soc. Rev. 2009, 38, 976– 989 DOI: 10.1039/b809132n
Google Scholar
19
Recent advances in the chemistry of lanthanide-doped upconversion nanocrystals
Wang, Feng; Liu, Xiaogang
Chemical Society Reviews (2009), 38 (4), 976-989CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)
A review. Lanthanide ions exhibit unique luminescent properties, including the ability to convert near IR long-wavelength excitation radiation into shorter visible wavelengths through a process known as photon upconversion. In recent years lanthanide-doped upconversion nanocrystals were developed as a new class of luminescent optical labels that have become promising alternatives to org. fluorophores and quantum dots for applications in biol. assays and medical imaging. These techniques offer low autofluorescence background, large anti-Stokes shifts, sharp emission bandwidths, high resistance to photobleaching, and high penetration depth and temporal resoln. Such techniques also show potential for improving the selectivity and sensitivity of conventional methods. They also pave the way for high throughput screening and miniaturization. This tutorial review focuses on the recent development of various synthetic approaches and possibilities for chem. tuning of upconversion properties, as well as giving an overview of biol. applications of these luminescent nanocrystals.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXjsFaisr4%253D&md5=6a5e2b96c141b9c8191bf9a6e139a15b
20
Liu, C.; Wang, H.; Li, X.; Chen, D. Monodisperse, Size-Tunable and Highly Efficient β-NaYF4:Yb,Er(Tm) up-Conversion Luminescent Nanospheres: Controllable Synthesis and Their Surface Modifications J. Mater. Chem. 2009, 19, 3546– 3553 DOI: 10.1039/b820254k
Google Scholar
20
Monodisperse, size-tunable and highly efficient β-NaYF4:Yb,Er(Tm) up-conversion luminescent nanospheres: controllable synthesis and their surface modifications
Liu, Chenghui; Wang, Hui; Li, Xiao; Chen, Depu
Journal of Materials Chemistry (2009), 19 (21), 3546-3553CODEN: JMACEP; ISSN:0959-9428. (Royal Society of Chemistry)
Monodisperse, oil-dispersible β-NaYF4:Yb,Er(Tm) up-conversion (UC) luminescent nanospheres (NPs) were successfully synthesized. The as-prepd. NPs show high size-uniformity without any size-selection process, and the sizes of the NPs can be tuned in 18-45 nm, which are well suitable for biolabels. The NPs are thoroughly characterized and a growth mechanism is proposed. By co-doping Yb-Er or Yb-Tm, the as-prepd. NPs can show bright green or blue UC luminescence under the irradn. of a 980. nm near-IR (NIR) laser, and the UC luminescence can be obviously enhanced by constructing a NaYF4:Yb,Er@NaYF4 core/shell structure. Also, the hydrophobic UC nanospheres (UCNPs) are converted into H2O-sol. by a robust ligand-exchange pathway with poly(acrylic acid). The presence of free carboxylic acid groups on their surfaces not only results in high soly. in H2O, but also allows further conjugation with biomols. such as antigens, antibodies and oligonucleotides, which pave the way for potential bio-applications of the UCNPs.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXmtFCjsr0%253D&md5=eb45d95fe7fa741f5f371bb444bb84d6
21
Liu, B.; Chen, Y.; Li, C.; He, F.; Hou, Z.; Huang, S.; Zhu, H.; Chen, X.; Lin, J. Poly(Acrylic Acid) Modification of Nd³⁺ -Sensitized Upconversion Nanophosphors for Highly Efficient UCL Imaging and pH-Responsive Drug Delivery Adv. Funct. Mater. 2015, 25, 4717– 4729 DOI: 10.1002/adfm.201501582
Google Scholar
There is no corresponding record for this reference.
22
Zhang, C.; Yuan, Y.; Zhang, S.; Wang, Y.; Liu, Z. Biosensing Platform Based on Fluorescence Resonance Energy Transfer from Upconverting Nanocrystals to Graphene Oxide Angew. Chem., Int. Ed. Engl. 2011, 50, 6851– 6854 DOI: 10.1002/anie.201100769
Google Scholar
There is no corresponding record for this reference.
23
Wu, S.; Duan, N.; Ma, X.; Xia, Y.; Wang, H.; Wang, Z.; Zhang, Q. Multiplexed Fluorescence Resonance Energy Transfer Aptasensor between Upconversion Nanoparticles and Graphene Oxide for the Simultaneous Determination of Mycotoxins Anal. Chem. 2012, 84, 6263– 6270 DOI: 10.1021/ac301534w
Google Scholar
23
Multiplexed Fluorescence Resonance Energy Transfer Aptasensor between Upconversion Nanoparticles and Graphene Oxide for the Simultaneous Determination of Mycotoxins
Wu, Shijia; Duan, Nuo; Ma, Xiaoyuan; Xia, Yu; Wang, Hongxin; Wang, Zhouping; Zhang, Qian
Analytical Chemistry (Washington, DC, United States) (2012), 84 (14), 6263-6270CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)
We presented a new aptasensor for mycotoxins, which was based on multiplexed fluorescence resonance energy transfer (FRET) between multicolor upconversion fluorescent nanoparticles (UCNPs) as donors and graphene oxide (GO) as the entire and effective acceptor. BaY0.78F5:Yb0.2,Er0.02 and BaY0.78F5:Yb0.7,Tm0.02 upconversion nanoparticles were synthesized and functionalized, resp., with immobilized ochratoxin A (OTA)-aptamers and fumonisin B1 (FB1)-aptamers. On the basis of the strong π-π stacking effect between the nucleobases of the aptamers and the sp2 atoms of GO, the aptamer modified-UCNPs can be brought in close proximity to the GO surface. The strong upconversion fluorescence both of BaY0.78F5:Yb0.2, Er0.02 and BaY0.78F5:Yb0.2, Tm0.02 can be completely quenched by the GO, because of a good overlap between the fluorescence emission of multicolor UCNPs and the absorption spectrum of GO. In contrast, in the presence of OTA and FB1, the aptamers preferred to bind to their corresponding mycotoxins, which led to changes in the formation of aptamers, and therefore, aptamer modified-UCNPs were far away from the GO surface. Our study results showed that the fluorescence intensity of BaYF5:Yb Er and BaYF5:Yb Tm were related to the concn. of OTA and FB1. We therefore developed a sensitive and simple platform for the simultaneous detection of OTA and FB1 with multicolor UCNPs and GO as the FRET pair. The aptasensor provided a linear range from 0.05 to 100 ng·mL-1 for OTA and 0.1 to 500 ng·mL-1 for FB1; the detection limit of OTA was 0.02 ng·mL-1 and FB1 was 0.1 ng·mL-1. As a practical application, the aptasensor was used to monitor OTA and FB1 level in naturally contaminated maize samples with the results consistent with that of a classic ELISA method. More importantly, the novel multiplexed FRET was established for the first time based on multiplexed energy donors to the entire energy acceptor; this work was expected to open up a new field of FRET system applications for various targets.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XptFSqt74%253D&md5=8de949b0a57d38397bd208e0b3233a77
24
Sedlmeier, A.; Gorris, H. H. Surface Modification and Characterization of Photon-Upconverting Nanoparticles for Bioanalytical Applications Chem. Soc. Rev. 2015, 44, 1526– 1560 DOI: 10.1039/C4CS00186A
Google Scholar
24
Surface modification and characterization of photon-upconverting nanoparticles for bioanalytical applications
Sedlmeier, Andreas; Gorris, Hans H.
Chemical Society Reviews (2015), 44 (6), 1526-1560CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)
A review. Photon-upconverting nanoparticles (UCNPs) can be excited by near-IR light and emit visible light (anti-Stokes emission) which prevents autofluorescence and light scattering of biol. samples. The potential for background-free imaging has attracted wide interest in UCNPs in recent years. Small and homogeneous lanthanide-doped UCNPs that display high upconversion efficiency have typically been synthesized in org. solvents. Bioanal. applications, however, require a subsequent phase transfer to aq. solns. Hence, the surface properties of UCNPs must be well designed and characterized to grant both a stable aq. colloidal dispersion and the ability to conjugate biomols. and other ligands on the nanoparticle surface. In this review, we introduce various routes for the surface modification of UCNPs and critically discuss their advantages and disadvantages. The last part covers various anal. methods that enable a thorough examn. of the progress and success of the surface functionalization.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsVGjur7K&md5=103ff17432cb75c8fa71ea384111f65e
25
Doughan, S.; Han, Y.; Uddayasankar, U.; Krull, U. J. Solid-Phase Covalent Immobilization of Upconverting Nanoparticles for Biosensing by Luminescence Resonance Energy Transfer ACS Appl. Mater. Interfaces 2014, 6, 14061– 14068 DOI: 10.1021/am503391m
Google Scholar
25
Solid-Phase Covalent Immobilization of Upconverting Nanoparticles for Biosensing by Luminescence Resonance Energy Transfer
Doughan, Samer; Han, Yi; Uddayasankar, Uvaraj; Krull, Ulrich J.
ACS Applied Materials & Interfaces (2014), 6 (16), 14061-14068CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)
Monodisperse water-sol. upconverting nanoparticles (UCNPs) were immobilized onto modified glass substrates for development of biosensing surfaces that operated using luminescence resonance energy transfer (LRET). Amine modified UCNPs were prepd. from oleic acid capped UCNPs by ligand exchange using o-phosphorylethanolamine (PEA). PEA-UCNPs were covalently immobilized on aldehyde functionalized coverslips. Environmental SEM (ESEM) images indicated a homogeneous distribution of UCNPs on surfaces with a high immobilization d. of approx. 1.3 × 1011 UCNP cm-2. This is the first account of covalent immobilization of UCNPs for bioassay and biosensor development where the d. is on par with the high immobilization densities reported for other types of nanoparticles. The functionality and stability of the immobilized NPs were demonstrated by examg. an LRET-based bioassay. The well-known sandwich assay for the detection of thrombin was selected as a model in which UCNPs were used as donors and quantum dots (QDs) as acceptors. The closely packed UCNPs on the glass surface showed a 2.5-fold enhancement in assay sensitivity compared to less-densely packed surfaces. In addn., a 1.5-fold enhancement in energy transfer efficiency was shown for solid-phase compared to soln.-phase LRET.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtFOqtbrO&md5=f3bf8690004507e37459b076003cc3d8
26
Sedlmeier, A.; Hlavek, A.; Birner, L.; Mickert, M. J.; Muhr, V.; Hirsch, T.; Corstjens, P. L. A. M.; Tanke, H. J.; Soukka, T.; Gorris, H. H. Highly Sensitive Laser Scanning of Photon-Upconverting Nanoparticles on a Macroscopic Scale Anal. Chem. 2016, 88, 1835– 1841 DOI: 10.1021/acs.analchem.5b04147
Google Scholar
26
Highly Sensitive Laser Scanning of Photon-Upconverting Nanoparticles on a Macroscopic Scale
Sedlmeier, Andreas; Hlavacek, Antonin; Birner, Lucia; Mickert, Matthias J.; Muhr, Verena; Hirsch, Thomas; Corstjens, Paul L. A. M.; Tanke, Hans J.; Soukka, Tero; Gorris, Hans H.
Analytical Chemistry (Washington, DC, United States) (2016), 88 (3), 1835-1841CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)
An upconversion laser scanner has been optimized to exploit the advantages of photon-upconverting nanoparticles (UCNPs) for background-free imaging on a macroscopic scale. A collimated 980 nm laser beam afforded high local excitation densities to account for the nonlinear luminescence response of UCNPs. As few as 2000 nanoparticles were detectable, and the linear dynamic range covered more than 5 orders of magnitude, which is essentially impossible by using conventional fluorescent dyes. UCNPs covered by a dye-doped silica shell were sepd. by agarose gel electrophoresis and scanned by a conventional fluorescence scanner as well as the upconversion scanner. Both optical labels could be detected independently. Finally, upconversion images of lateral flow test strips were recorded to facilitate the sensitive and quant. detection of disease markers. A marker for the parasitic worm Schistosoma was used in this study.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXitV2nsbzK&md5=abbab3239a2114b4d7bb3bd9c09bc27b
27
Kale, V.; Päkkilä, H.; Vainio, J.; Ahomaa, A.; Sirkka, N.; Lyytikäinen, A.; Talha, S. M.; Kutsaya, A.; Waris, M.; Julkunen, I.; Soukka, T. Spectrally and Spatially Multiplexed Serological Array-in-Well Assay Utilizing Two-Color Upconversion Luminescence Imaging Anal. Chem. 2016, 88, 4470– 4477 DOI: 10.1021/acs.analchem.6b00337
Google Scholar
27
Spectrally and Spatially Multiplexed Serological Array-in-Well Assay Utilizing Two-Color Upconversion Luminescence Imaging
Kale, Vishal; Pakkila, Henna; Vainio, Jiri; Ahomaa, Anna; Sirkka, Nina; Lyytikainen, Annika; Talha, Sheikh Mohammad; Kutsaya, Anna; Waris, Matti; Julkunen, Ilkka; Soukka, Tero
Analytical Chemistry (Washington, DC, United States) (2016), 88 (8), 4470-4477CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)
We demonstrate a simple dual-mode multiplexed array-in-well immunoassay for simultaneous classification and detection of serum IgG and IgM antibodies against influenza A and human adenoviruses based on the color and position of the upconversion luminescence on the array. Biotinylated influenza A/H1N1 and A/H5N1 as well as adenovirus serotype 2 and 5 hexon antigens along with pos. and neg. controls were printed in an array format onto the bottom of streptavidin-coated microtiter wells. The anti-influenza A and antiadenovirus antibodies present in the sample were captured to the array and detected with antihuman antibody-coated upconverting nanophosphors (UCNPs). The green emitting UCNPs (NaYF4:Yb3+,Er3+) coated with antihuman IgG and blue emitting UCNPs (NaYF4:Yb3+,Tm3+) coated with antihuman IgM were used to detect human IgG and IgM antibodies, resp. The emission of the bound UCNPs was imaged free of autofluorescence with anti-Stokes photoluminescence microwell imager. No spectral cross-talk was obsd. between green and blue emitting UCNPs. Also the cross-reactivities between UCNP-conjugates and immobilized human IgG and IgM antibodies were negligible. Position of the signal on the array defined the antigen specificity and the antibody class was defined by the color of the upconversion luminescence. This technol. could be used for differentiation between acute infection from past infection and immunity. Addnl., the class of the antibody response can be used for the differentiation between primary and secondary infections, hence, facilitating epidemiol. seroprevalence studies.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XksVGrsLY%253D&md5=5c9bce5cfcde3e4e1837fbb85fab8f24
28
Ylihärsilä, M.; Valta, T.; Karp, M.; Hattara, L.; Harju, E.; Hölsä, J.; Saviranta, P.; Waris, M.; Soukka, T. Oligonucleotide Array-in-Well Platform for Detection and Genotyping Human Adenoviruses by Utilizing Upconverting Phosphor Label Technology Anal. Chem. 2011, 83, 1456– 1461 DOI: 10.1021/ac103155f
Google Scholar
There is no corresponding record for this reference.
29
van de Rijke, F.; Zijlmans, H.; Li, S.; Vail, T.; Raap, A. K.; Niedbala, R. S.; Tanke, H. J. Up-converting Phosphor Reporters for Nucleic Acid Microarrays Nat. Biotechnol. 2001, 19, 273– 276 DOI: 10.1038/85734
Google Scholar
29
Up-converting phosphor reporters for nucleic acid microarrays
van de Rijke, Frans; Zijlmans, Henry; Li, Shang; Vail, Tim; Raap, Anton K.; Niedbala, R. Sam; Tanke, Hans J.
Nature Biotechnology (2001), 19 (3), 273-276CODEN: NABIF9; ISSN:1087-0156. (Nature America Inc.)
An important application of robotically spotted DNA microarrays is the monitoring of RNA expression levels. A clear limitation of this technol. is the relatively large amt. of RNA that is required per hybridization as a result of low hybridization efficiency and limiting detection sensitivity provided by conventional fluorescent reporters. We have used a recently introduced luminescent reporter technol., called UPT (up-converting phosphor technol.). Down-converting phosphors have been applied before to detect nucleic acids on filters using time-resolved fluorometry. The unique feature of the phosphor particles (size 0.4 μm) used here is that they emit visible light when illuminated with IR (IR) light (980 nm) as a result of a phenomenon called up-conversion. Because neither support material of microarrays nor biomols. possess up-conversion properties, an enhanced image contrast is expected when these nonfading phosphor particles are applied to detect nucleic acid hybrids on microarrays. Comparison of the UPT reporter to cyanine 5 (Cy5), in a low-complexity model system showed a two order of magnitude linear relationship between phosphor luminescence and target concn. and resulted in an excellent correlation between the two reporter systems for variable target concns. (R2 = 0.95). However, UPT proved to be superior in sensitivity, even though a wide-field microscope equipped with a xenon lamp was used. This higher sensitivity was demonstrated by complementary DNA (cDNA) microarray hybridizations using cDNAs for housekeeping genes as probes and complex cDNA as target. These results suggest that UPT reporter technol. in combination with a dedicated IR laser array-scanner holds significant promise for various microarray applications.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3MXhslejs7g%253D&md5=49aaef5decb0b894d0a6a050a6a6bcb2
30
Hlaváček, A.; Farka, Z.; Hübner, M.; Horňáková, V.; Němeček, D.; Niessner, R.; Skládal, P.; Knopp, D.; Gorris, H. H. Competitive Upconversion-Linked Immunosorbent Assay for the Sensitive Detection of Diclofenac Anal. Chem. 2016, 88, 6011– 6017 DOI: 10.1021/acs.analchem.6b01083
Google Scholar
30
Competitive Upconversion-Linked Immunosorbent Assay for the Sensitive Detection of Diclofenac
Hlavacek, Antonin; Farka, Zdenek; Huebner, Maria; Hornakova, Veronika; Nemecek, Daniel; Niessner, Reinhard; Skladal, Petr; Knopp, Dietmar; Gorris, Hans H.
Analytical Chemistry (Washington, DC, United States) (2016), 88 (11), 6011-6017CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)
Photon-upconverting nanoparticles (UCNPs) emit light of shorter wavelength under near-IR excitation and thus avoid optical background interference. We have exploited this unique photophys. feature to establish a sensitive competitive immunoassay for the detection of the pharmaceutical micropollutant diclofenac (DCF) in water. The so-called upconversion-linked immunosorbent assay (ULISA) was critically dependent on the design of the upconversion luminescent detection label. Silica-coated UCNPs (50 nm in diam.) exposing carboxyl groups on the surface were conjugated to a secondary anti-IgG antibody. We investigated the structure and monodispersity of the nanoconjugates in detail. Using a highly affine anti-DCF primary antibody, the optimized ULISA reached a detection limit of 0.05 ng DCF per mL. This performance came close to a conventional ELISA (ELISA) without the need for an enzyme-mediated signal amplification step. The ULISA was further employed for analyzing drinking and surface water samples. The results were were consistent with a conventional ELISA as well as liq. chromatog.-mass spectrometry (LC-MS).
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XnslCru7Y%253D&md5=c13c4d145820a8fd0358805b9af4f11d
31
El-Sagheer, A. H.; Brown, T. Click Chemistry with DNA Chem. Soc. Rev. 2010, 39, 1388– 1405 DOI: 10.1039/b901971p
Google Scholar
31
Click chemistry with DNA
El-Sagheer, Afaf H.; Brown, Tom
Chemical Society Reviews (2010), 39 (4), 1388-1405CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)
A review. The advent of click chem. has led to an influx of new ideas in the nucleic acids field. The copper catalyzed alkyne-azide cycloaddn. (CuAAC) reaction is the method of choice for DNA click chem. due to its remarkable efficiency. It was used to label oligonucleotides with fluorescent dyes, sugars, peptides and other reporter groups, to cyclize DNA, to synthesize DNA catenanes, to join oligonucleotides to PNA, and to produce analogs of DNA with modified nucleobases and backbones. In this crit. review the authors describe some of the pioneering work that was carried out in this area (78 refs.).
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXjs1Ggtbk%253D&md5=686633602294b9f76f289e8d97ecd737
32
Hulme, E. C.; Trevethick, M. A. Ligand Binding Assays at Equilibrium: Validation and Interpretation Br. J. Pharmacol. 2010, 161, 1219– 1237 DOI: 10.1111/j.1476-5381.2009.00604.x
Google Scholar
32
Ligand binding assays at equilibrium: validation and interpretation
Hulme, Edward C.; Trevethick, Mike A.
British Journal of Pharmacology (2010), 161 (6), 1219-1237CODEN: BJPCBM; ISSN:1476-5381. (Wiley-Blackwell)
The focus of this review paper is factors affecting data interpretation in ligand binding assays under equil. conditions. Protocols for detg. Kd (the equil. dissocn. const.) and KdA (the equil. inhibitor const.) for receptor ligands are discussed. The basic theory describing the interaction of a radiotracer and an unlabeled competitor ligand with a receptor is developed. Inappropriate exptl. design may result in ligand depletion and non-attainment of equil., distorting the calcn. of Kd and KdA. Strategies, both theor. and practical, will be given to avoid and correct such errors, thus leading to the detn. of reliable values for these consts. In detg. KdA from competition binding studies, two addnl. concepts are discussed. First, the necessity to measure an adequate specific binding signal from the bound radiotracer ligand limits the range of affinity consts. that can be measured: a particular set of assay conditions may lead to an upper limit on the apparent affinity of unlabeled ligands. Second, an extension of the basic assay methodol. can indicate whether the interaction between the tracer and a test ligand is mediated by a competitive or an allosteric mechanism. Finally, the review ends with a discussion of two factors that are often overlooked: buffer compn. and the temp. at which the assay is conducted, and the impact these can have on affinity measurements and the understanding of drug interactions.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhsFWhsr3J&md5=03875d96fbc7ae409b8f4c8a084dbc99
33
Broder, G. R.; Ranasinghe, R. T.; Neylon, C.; Morgan, H.; Roach, P. L. Kinetics and Thermodynamics of Biotinylated Oligonucleotide Probe Binding to Particle-Immobilized Avidin and Implications for Multiplexing Applications Anal. Chem. 2011, 83, 2005– 2011 DOI: 10.1021/ac102762q
Google Scholar
33
Kinetics and Thermodynamics of Biotinylated Oligonucleotide Probe Binding to Particle-Immobilized Avidin and Implications for Multiplexing Applications
Broder, Graham R.; Ranasinghe, Rohan T.; Neylon, Cameron; Morgan, Hywel; Roach, Peter L.
Analytical Chemistry (Washington, DC, United States) (2011), 83 (6), 2005-2011CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)
In this work, the kinetics and dissocn. const. for the binding of a biotin-modified oligonucleotide to microparticle-immobilized avidin were measured. Avidin has been immobilized by both covalent coupling and bioaffinity capture to a surface prefunctionalized with biotin. The measured rate and equil. dissocn. consts. of avidin immobilized by these different methods have been compared with those for nonimmobilized avidin. The authors found that immobilization resulted in both a decrease in the rate of binding and an increase in the rate of dissocn. leading to immobilized complexes having equil. dissocn. consts. of 7±3 × 10-12 M, higher than the value measured for the complex between biotin-modified oligonucleotide and nonimmobilized avidin and approx. 4 orders of magnitude larger than values for the wild-type avidin-biotin complex. Immobilized complex half-lives were reduced to 5 days, which resulted in biotin ligands migrating between protein attached to different particles. Different immobilization methods showed little variation in complex stability but differed in total binding and nonspecific biotin-modified oligonucleotide binding. These findings are crit. for the design of multiplexed assays where probe mols. are immobilized to biosensors via the avidin-biotin interaction.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhsVektLs%253D&md5=beef8a51efd3dea3fcbe330c152c3e77
34
Noor, M. O.; Krull, U. J. Camera-Based Ratiometric Fluorescence Transduction of Nucleic Acid Hybridization with Reagentless Signal Amplification on a Paper-Based Platform Using Immobilized Quantum Dots as Donors Anal. Chem. 2014, 86, 10331– 10339 DOI: 10.1021/ac502677n
Google Scholar
34
Camera-Based Ratiometric Fluorescence Transduction of Nucleic Acid Hybridization with Reagentless Signal Amplification on a Paper-Based Platform Using Immobilized Quantum Dots as Donors
Noor, M. Omair; Krull, Ulrich J.
Analytical Chemistry (Washington, DC, United States) (2014), 86 (20), 10331-10339CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)
Paper-based diagnostic assays are gaining increasing popularity for their potential application in resource-limited settings and for point-of-care screening. Achievement of high sensitivity with precision and accuracy can be challenging when using paper substrates. Herein, the authors implement the red-green-blue color palette of a digital camera for quant. ratiometric transduction of nucleic acid hybridization on a paper-based platform using immobilized quantum dots (QDs) as donors in fluorescence resonance energy transfer (FRET). A nonenzymic and reagentless means of signal enhancement for QD-FRET assays on paper substrates is based on the use of dry paper substrates for data acquisition. This approach offered at least a 10-fold higher assay sensitivity and at least a 10-fold lower limit of detection (LOD) as compared to hydrated paper substrates. The surface of paper was modified with imidazole groups to assemble a transduction interface that consisted of immobilized QD-probe oligonucleotide conjugates. Green-emitting QDs (gQDs) served as donors with Cy3 as an acceptor. A hybridization event that brought the Cy3 acceptor dye in close proximity to the surface of immobilized gQDs was responsible for a FRET-sensitized emission from the acceptor dye, which served as an anal. signal. A hand-held UV lamp was used as an excitation source and ratiometric anal. using an iPad camera was possible by a relative intensity anal. of the red (Cy3 photoluminescence (PL)) and green (gQD PL) color channels of the digital camera. For digital imaging using an iPad camera, the LOD of the assay in a sandwich format was 450 fmol with a dynamic range spanning 2 orders of magnitude, while an epifluorescence microscope detection platform offered a LOD of 30 fmol and a dynamic range spanning 3 orders of magnitude. The selectivity of the hybridization assay was demonstrated by detection of a single nucleotide polymorphism at a contrast ratio of 60:1. This work provides an important framework for the integration of QD-FRET methods with digital imaging for a ratiometric transduction of nucleic acid hybridization on a paper-based platform.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsFKns77P&md5=e37bec4a9c00170d444fc47adf9cfaaa
35
Yang, Y.; Li, C.; Yin, L.; Liu, M.; Wang, Z.; Shu, Y.; Li, G. Enhanced Charge Transfer by Gold Nanoparticle at DNA Modi Fi Ed Electrode and Its Application to Label-Free DNA Detection ACS Appl. Mater. Interfaces 2014, 6, 7579– 7584 DOI: 10.1021/am500912m
Google Scholar
There is no corresponding record for this reference.
36
Kang, T.; Yoo, S. M.; Yoon, I.; Lee, S. Y.; Kim, B. Patterned Multiplex Pathogen DNA Detection by Au Particle-on-Wire SERS Sensor Nano Lett. 2010, 10, 1189– 1193 DOI: 10.1021/nl1000086
Google Scholar
36
Patterned multiplex pathogen DNA detection by Au particle-on-wire SERS sensor
Kang, Taejoon; Yoo, Seung Min; Yoon, Ilsun; Lee, Sang Yup; Kim, Bongsoo
Nano Letters (2010), 10 (4), 1189-1193CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)
A gold particle-on-wire system that can be used as a specific, sensitive, and multiplex DNA sensor is developed. A pattern formed by multiple Au nanowire sensors provides positional address and identification for each sensor. By using this system, multiplex sensing of target DNAs was possible in a quant. manner with a detection limit of 10 pM. Target DNAs from ref. bacteria and clin. isolates were successfully identified by this sensor system, enabling diagnostics for infectious diseases.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXjtFSjs7g%253D&md5=79134bae75d137af1c56341a3d3b7168
37
López, M. S.; Cabanillas, G. F.; Castañón, M. J. L.; López-Ruiz, B. Development of a Genosensor for Peanut Allergen ARA H 2 Detection and Its Optimization by Surface Response Methodology Biosens. Bioelectron. 2014, 62, 350– 356 DOI: 10.1016/j.bios.2014.06.065
Google Scholar
There is no corresponding record for this reference.
38
Du, Y.; Guo, S.; Dong, S.; Wang, E. An Integrated Sensing System for Detection of DNA Using New Parallel-Motif DNA Triplex System and Graphene-Mesoporous Silica-Gold Nanoparticle Hybrids Biomaterials 2011, 32, 8584– 8592 DOI: 10.1016/j.biomaterials.2011.07.091
Google Scholar
38
An integrated sensing system for detection of DNA using new parallel-motif DNA triplex system and graphene-mesoporous silica-gold nanoparticle hybrids
Du, Yan; Guo, Shaojun; Dong, Shaojun; Wang, Erkang
Biomaterials (2011), 32 (33), 8584-8592CODEN: BIMADU; ISSN:0142-9612. (Elsevier Ltd.)
In this article, we demonstrate the use of graphene-mesoporous silica-gold NP hybrids (GSGHs) as an enhanced element of the integrated sensing platform for the ultra-sensitive and selective detection of DNA by using strand-displacement DNA polymn. and parallel-motif DNA triplex system as dual amplifications. We find that the present new sensing strategy based on GSGHs is able to detect target DNA with a fairly high detection sensitivity of 10 fm through the hybridization of duplex DNA to the acceptor DNA for the formation of parallel-motif DNA triplex on the multilayer film (contg. GSGHs and redox probe) modified functional interface, and even has a good capability to investigate the single nucleotide polymorphisms (SNPs). The detection limit for target DNA is about two orders of magnitude lower than that of graphene-based DNA electrochem. impedance spectroscopy (EIS) sensor (6.6 pm), four orders of magnitude lower than those of graphene-based DNA sensors coupled with fluorescent assay (100 pm and 1 nm) and five orders of magnitude lower than those of field effect transistor (FET)-based assays (1 nm and 2 nm). Most importantly, our present sensing system can also be facilely achieved in the ITO electrode array, which is of paramount importance for possible multiplex anal. in lab-on-chip.
>> More from SciFinder ^®
https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhtFOlsrrE&md5=bf41573654fe52b413f8287c89889293

Cited By

Click to copy section linkSection link copied!

This article is cited by 32 publications.

Huimin Yuan, Jinping Hu, Qi-qin Ge, Wen-jing Liu, Fei Ma, Chun-yang Zhang. Construction of a Spatial-Confined Self-Stacking Catalytic Circuit for Rapid and Sensitive Imaging of Piwi-Interacting RNA in Living Cells. Nano Letters 2024, 24 (28) , 8732-8740. https://doi.org/10.1021/acs.nanolett.4c02230
Kamaljit Kaur, Bandana Kumari Sahu, Kanchan Swami, Mahima Chandel, Anshika Gupta, Li-Hua Zhu, Jeffrey P. Youngblood, Selvaraju Kanagarajan, Vijayakumar Shanmugam. Phone Camera Nano-Biosensor Using Mighty Sensitive Transparent Reusable Upconversion Paper. ACS Applied Materials & Interfaces 2022, 14 (23) , 27507-27514. https://doi.org/10.1021/acsami.2c06894
Lin Yang, Sha Yu, Yongcun Yan, Sai Bi, Jun-Jie Zhu. Upconversion Nanoparticle@Au Core–Satellite Assemblies for In Situ Amplified Imaging of MicroRNA in Living Cells and Combined Cancer Phototherapy. Analytical Chemistry 2022, 94 (19) , 7075-7083. https://doi.org/10.1021/acs.analchem.2c00477
Elsa Lu, Jothirmayanantham Pichaandi, Chandresh Kumar Rastogi, Mitchell A. Winnik. Effect of Excess Ligand on the Reverse Microemulsion Silica Coating of NaLnF4 Nanoparticles. Langmuir 2022, 38 (10) , 3316-3326. https://doi.org/10.1021/acs.langmuir.2c00372
Ludivine Taiariol, Carole Chaix, Carole Farre, Emmanuel Moreau. Click and Bioorthogonal Chemistry: The Future of Active Targeting of Nanoparticles for Nanomedicines?. Chemical Reviews 2022, 122 (1) , 340-384. https://doi.org/10.1021/acs.chemrev.1c00484
Rishabh Rastogi, Ekoue A. Dogbe Foli, Remi Vincent, Suresh Poovathingal, Pierre-Michel Adam, Sivashankar Krishnamoorthy. Hierarchically Structured Plasmonic Nanoparticle Assemblies with Dual-Length Scale Electromagnetic Hot Spots for Enhanced Sensitivity in the Detection of (Bio)Molecular Analytes. The Journal of Physical Chemistry C 2021, 125 (16) , 8647-8655. https://doi.org/10.1021/acs.jpcc.0c10467
Mingyuan Yin, Chen Wu, Haijie Li, Zhixin Jia, Qiliang Deng, Shuo Wang, Yukui Zhang. Simultaneous Sensing of Seven Pathogenic Bacteria by Guanidine-Functionalized Upconversion Fluorescent Nanoparticles. ACS Omega 2019, 4 (5) , 8953-8959. https://doi.org/10.1021/acsomega.9b00775
Zhiming Zhang, Swati Shikha, Jinliang Liu, Jing Zhang, Qingsong Mei, Yong Zhang. Upconversion Nanoprobes: Recent Advances in Sensing Applications. Analytical Chemistry 2019, 91 (1) , 548-568. https://doi.org/10.1021/acs.analchem.8b04049
Diego Mendez-Gonzalez, Satu Lahtinen, Marco Laurenti, Enrique López-Cabarcos, Jorge Rubio-Retama, Tero Soukka. Photochemical Ligation to Ultrasensitive DNA Detection with Upconverting Nanoparticles. Analytical Chemistry 2018, 90 (22) , 13385-13392. https://doi.org/10.1021/acs.analchem.8b03106
Birui Jin, Chuyao Zhang, Chuan Ma, Huiling Yin, Siyu Li, Zhiguo Du, Guoxu Zhao, Huimei Huang, Zedong Li. Innovative strategies and approaches for enhancing performance in optical probe-based biosensors for point-of-care testing. TrAC Trends in Analytical Chemistry 2024, 176 , 117775. https://doi.org/10.1016/j.trac.2024.117775
Alejandro Casillas-Rubio, Diego Mendez-Gonzalez, Marco Laurenti, Jorge Rubio-Retama, Oscar G. Calderón, Sonia Melle. Impact of excitation pulse width on the upconversion luminescence lifetime of NaYF 4 :Yb 3+ ,Er 3+ nanoparticles. Nanoscale 2024, 16 (25) , 12184-12195. https://doi.org/10.1039/D4NR00718B
Elena Sanz-de Diego, Antonio Aires, Pablo Palacios-Alonso, David Cabrera, Niccolo Silvestri, Cinthia C. Vequi-Suplicy, Emilio J. Artés-Ibáñez, José Requejo-Isidro, Rafael Delgado-Buscalioni, Teresa Pellegrino, Aitziber L. Cortajarena, Francisco J. Terán. Multiparametric modulation of magnetic transduction for biomolecular sensing in liquids. Nanoscale 2024, 16 (8) , 4082-4094. https://doi.org/10.1039/D3NR06489A
Pablo Palacios-Alonso, Elena Sanz-de-Diego, Raúl P. Peláez, A. L. Cortajarena, F. J. Teran, Rafael Delgado-Buscalioni. Predicting the size and morphology of nanoparticle clusters driven by biomolecular recognition. Soft Matter 2023, 19 (46) , 8929-8944. https://doi.org/10.1039/D3SM00536D
Yuchun Guo, Jiangtao Ren, Erkang Wang. DNA‐Encoded Nanomaterials with Controllable Properties. Analysis & Sensing 2023, 3 (3) https://doi.org/10.1002/anse.202200067
Yueying Cao, Jiehua Wu, Xianlin Zheng, Yanling Lu, James A. Piper, Yiqing Lu, Nicolle H. Packer. Assessing the activity of antibodies conjugated to upconversion nanoparticles for immunolabeling. Analytica Chimica Acta 2022, 1209 , 339863. https://doi.org/10.1016/j.aca.2022.339863
María López-Valls, Carmen Escalona-Noguero, Ciro Rodríguez-Díaz, Demian Pardo, Milagros Castellanos, Paula Milán-Rois, Carlos Martínez-Garay, Rocío Coloma, Melanie Abreu, Rafael Cantón, Juan Carlos Galán, Rodolfo Miranda, Álvaro Somoza, Begoña Sot. CASCADE: Naked eye-detection of SARS-CoV-2 using Cas13a and gold nanoparticles. Analytica Chimica Acta 2022, 1205 , 339749. https://doi.org/10.1016/j.aca.2022.339749
Chunning Sun, Michael Gradzielski. Advances in fluorescence sensing enabled by lanthanide-doped upconversion nanophosphors. Advances in Colloid and Interface Science 2022, 300 , 102579. https://doi.org/10.1016/j.cis.2021.102579
Pandiyaraj Kanagavalli, Chrysanthus Andrew, Murugan Veerapandian, Mani Jayakumar. In-situ redox-active hybrid graphene platform for label-free electrochemical biosensor: Insights from electrodeposition and electroless deposition. TrAC Trends in Analytical Chemistry 2021, 143 , 116413. https://doi.org/10.1016/j.trac.2021.116413
Vivian Torres Vera, Diego Mendez-Gonzalez, Diego J. Ramos-Ramos, Asmae Igalla, Marco Laurenti, Rafael Contreras-Caceres, Enrique Lopez-Cabarcos, Elena Díaz, Jorge Rubio-Retama, Sonia Melle, Oscar G. Calderón. The effects of dopant concentration and excitation intensity on the upconversion and downconversion emission processes of β-NaYF 4 :Yb 3+ ,Er 3+ nanoparticles. Journal of Materials Chemistry C 2021, 9 (28) , 8902-8911. https://doi.org/10.1039/D1TC01419F
Anees A Ansari, Vijay K. Thakur, Guanying Chen. Functionalized upconversion nanoparticles: New strategy towards FRET-based luminescence bio-sensing. Coordination Chemistry Reviews 2021, 436 , 213821. https://doi.org/10.1016/j.ccr.2021.213821
Aastha Kukreja, Byunghoon Kang, Seungmin Han, Moo-Kwang Shin, Hye Young Son, Yuna Choi, Eun-Kyung Lim, Yong-Min Huh, Seungjoo Haam. Inner structure- and surface-controlled hollow MnO nanocubes for high sensitive MR imaging contrast effect. Nano Convergence 2020, 7 (1) https://doi.org/10.1186/s40580-020-00227-6
Diego Mendez-Gonzalez, Oscar G. Calderón, Sonia Melle, Jesús González-Izquierdo, Luis Bañares, David López-Díaz, M. Mercedes Velázquez, Enrique López-Cabarcos, Jorge Rubio-Retama, Marco Laurenti. Contribution of resonance energy transfer to the luminescence quenching of upconversion nanoparticles with graphene oxide. Journal of Colloid and Interface Science 2020, 575 , 119-129. https://doi.org/10.1016/j.jcis.2020.04.076
Thomas L. Derrien, Shogo Hamada, Max Zhou, Detlef-M. Smilgies, Dan Luo. Three-dimensional nanoparticle assemblies with tunable plasmonics via a layer-by-layer process. Nano Today 2020, 30 , 100823. https://doi.org/10.1016/j.nantod.2019.100823
Suresh Kumar Kailasa, Janardhan Reddy Koduru, Thriveni Thenepalli. Fabrication of Nanostructured Materials with Rare-Earth Elements for Bioanalytical Applications. 2020, 137-152. https://doi.org/10.1007/978-3-030-38106-6_7
Jie Hu, Kang Xiao, Birui Jin, Xuyang Zheng, Fanpu Ji, Dan Bai. Paper‐based point‐of‐care test with xeno nucleic acid probes. Biotechnology and Bioengineering 2019, 116 (10) , 2764-2777. https://doi.org/10.1002/bit.27106
Hong Zhou, Jing Liu, Jing-Juan Xu, Shusheng Zhang, Hong-Yuan Chen. Advances in DNA/RNA detection using nanotechnology. 2019, 31-98. https://doi.org/10.1016/bs.acc.2019.03.002
Alex Gee, Xiaoxue Xu. Surface Functionalisation of Upconversion Nanoparticles with Different Moieties for Biomedical Applications. Surfaces 2018, 1 (1) , 96-121. https://doi.org/10.3390/surfaces1010009
Keying Zhang, Shuting Song, Shan Huang, Lin Yang, Qianhao Min, Xingcai Wu, Feng Lu, Jun‐Jie Zhu. Lighting Up MicroRNA in Living Cells by the Disassembly of Lock‐Like DNA‐Programmed UCNPs‐AuNPs through the Target Cycling Amplification Strategy. Small 2018, 14 (40) https://doi.org/10.1002/smll.201802292
Keying Zhang, Lin Yang, Feng Lu, Xingcai Wu, Jun‐Jie Zhu. A Universal Upconversion Sensing Platform for the Sensitive Detection of Tumour‐Related ncRNA through an Exo III‐Assisted Cycling Amplification Strategy. Small 2018, 14 (10) https://doi.org/10.1002/smll.201703858
Diego Mendez-Gonzalez, Enrique Lopez-Cabarcos, Jorge Rubio-Retama, Marco Laurenti. Sensors and bioassays powered by upconverting materials. Advances in Colloid and Interface Science 2017, 249 , 66-87. https://doi.org/10.1016/j.cis.2017.06.003
Zhengzong Wu, Enbo Xu, Aiquan Jiao, Zhengyu Jin, Joseph Irudayaraj. Bimodal counterpropagating-responsive sensing material for the detection of histamine. RSC Advances 2017, 7 (71) , 44933-44944. https://doi.org/10.1039/C7RA07362C
Meral Yüce, Hasan Kurt. How to make nanobiosensors: surface modification and characterisation of nanomaterials for biosensing applications. RSC Adv. 2017, 7 (78) , 49386-49403. https://doi.org/10.1039/C7RA10479K

Download PDF

Get e-Alerts

ACS Applied Materials & Interfaces

Cite this: ACS Appl. Mater. Interfaces 2017, 9, 14, 12272–12281

Click to copy citationCitation copied!

https://doi.org/10.1021/acsami.7b00575

Published March 23, 2017

Article Views

Altmetric

Citations

Learn about these metrics

Article Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.

Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.

The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.

Abstract
High Resolution Image
Download MS PowerPoint Slide
Scheme 1
Scheme 1. Schematic Illustration of the Chemical Route for the Synthesis and Functionalization of NaYF₄:Yb,Er@SiO₂-DNA-N₃ Nanoparticles
High Resolution Image
Download MS PowerPoint Slide
Figure 1
Figure 1. TEM micrographs of the synthesized NaYF₄;Yb,Er nanoparticles (A) and NaYF₄;Yb,Er@SiO₂ nanoparticles (B). (C) HRTEM image of a NaYF₄;Yb,Er@SiO₂ nanoparticle. (D) Magnification of the image in (C). The scale bars in (A) and (B) are 50 nm, whereas in (C) and (D) they are 10 and 5 nm, respectively.
High Resolution Image
Download MS PowerPoint Slide
Scheme 2
Scheme 2. Schematic Illustration of the Action Mechanism of the Proposed Sensor^a
High Resolution Image
Download MS PowerPoint Slide
Scheme a(A) The presence of the target sequence allows the hybridization and brings in close proximity the azide group on probe 1 and the DBCO groups on probes 1 and 2 producing the SPAAC reaction that gives NaYF₄;Yb,Er@SiO₂-dsDNA-biotin nanoparticles. (B) Biotin moieties on the surface of the UCNPs allow their immobilization on the surface of the streptavidin-coated well-plates. (C) The fluorescence detection was performed using the homemade device.
Figure 2
Figure 2. Luminescence spectra obtained from NaYF₄;Yb,Er@SiO₂-ssDNA-N₃ and DBCO-ssDNA-biotin able to produce interstrand ligation (blue line) and NaYF₄;Yb,Er@SiO₂-ssDNA-N₃ and ssDNA-biotin, which are unable to produce interstrand ligation (red line), in the presence of 10^–13 moles per well (1 nM) of target sequence and after washing the solid support with 10 mM of HEPES buffer and different concentrations of NaCl at 50 °C: 150 mM in (A) and 50 mM in (B).
High Resolution Image
Download MS PowerPoint Slide
Figure 3
Figure 3. (A) Time evolution of the upconversion signal on the streptavidin-coated well-plate during the incubation process. The blue points correspond to the signal measured after incubating the biotin-functionalized UCNPs obtained from hybridization with 1 μg of probe 1 and 2 × 10^–12 moles of probe 2 with 10^–12 moles (10 nM) of target sequence per well. The red points represent the signal of the blank samples using the same procedure described before but without the target sequence. (B) Signal-to-background ratio (left axis) and signal-to-noise ratio (right axis) as a function of incubation time.
High Resolution Image
Download MS PowerPoint Slide
Figure 4
Figure 4. (A) Upconversion emission spectra collected from the multiwell-plate after being incubated with biotin-functionalized upconversion nanoparticles produced by hybridization with different amounts of target sequences. (B) Upconversion intensity collected from the multiwell-plate as a function of target concentration from 1 × 10^–18 to 1 × 10^–13 moles per well (10 fM to 1 nM). The signal intensity is blank subtracted. The error bars are the standard deviation obtained from measurements at 10 different positions on each well out of three independent samples for each target concentration. The blue dashed line indicates the LOD based on 3-fold SD of the blank samples.
High Resolution Image
Download MS PowerPoint Slide
Figure 5
Figure 5. A) Upconversion emission obtained from blank samples prepared in the presence of different amounts of total RNA from healthy mosquitoes and in the absence of target sequences. The red line indicates the average value 830 counts/s nm. (B) Upconversion emission obtained after hybridizing 1 μg of upconversion nanoparticles with 10^–12 moles per well of different sequences: full complementary sequences (Target), a sequence containing a single mismatch in the middle (MS1), a sequence containing three mismatches in the middle (MS2), a sequence containing a single mismatch in the first quarter of the strand (MS3), noncomplementary sequences (NCS), and in the absence of target sequences (BCK). The error bars indicate the standard deviation obtained from the experiments. (C) Upconversion intensity obtained after spiking samples containing 100 ng of total RNA with varying concentrations of target sequences. (D) Upconversion intensity obtained after spiking samples containing human serum with varying concentrations of target sequences. The intensities in (C) and (D) were blank subtracted and the blue dashed line indicates the threshold resulting from three times the standard deviation of the control signal. In all graphs, the error bars indicate the standard deviation.
High Resolution Image
Download MS PowerPoint Slide
Scheme 3
Scheme 3. Graphical Representation of the Possible Duplexes Formed^a
High Resolution Image
Download MS PowerPoint Slide
Scheme aThe mismatches bases are colored in red. Melting temperatures (T_m) of probes 1 and 2 with the target DNA and the mismatches DNA sequences were calculated using IDT SciTools.
References
This article references 38 other publications.
1. 1
  Fire, A.; Xu, S.; Montgomery, M. K.; Kostas, S. A.; Driver, S. E.; Mello, C. C. Potent and Specific Genetic Interference by Double-Stranded RNA in Caenorhabditis elegans Nature 1998, 391, 806– 811 DOI: 10.1038/35888
  1
  Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans
  Fire, Andrew; Xu, SiQun; Montgomery, Mary K.; Kostas, Steven A.; Driver, Samuel E.; Mello, Craig C.
  Nature (London) (1998), 391 (6669), 806-811CODEN: NATUAS; ISSN:0028-0836. (Macmillan Magazines)
  Exptl. introduction of RNA into cells can be used in certain biol. systems to interfere with the function of an endogenous gene. Such effects have been proposed to result from a simple antisense mechanism that depends on hybridization between the injected RNA and endogenous mRNA transcripts. RNA interference has been used in the nematode C. elegans to manipulate gene expression. Here we investigate the requirements for structure and delivery of the interfering RNA. To our surprise, we found that double-stranded RNA was substantially more effective at producing interference than was either strand individually. After injection into adult animals, purified single strands had at most a modest effect, whereas double-stranded mixts. caused potent and specific interference. The effects of this interference were evident in both the injected animals and their progeny. Only a few mols. of injected double-stranded RNA were required per affected cell, arguing against stoichiometric interference with endogenous mRNA and suggesting that there could be a catalytic or amplification component in the interference process.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK1cXhtlCju74%253D&md5=7bd291ca75d455bbbe1dee41c3362208
2. 2
  Hess, A. M.; Prasad, A. N.; Ptitsyn, A.; Ebel, G. D.; Olson, K. E.; Barbacioru, C.; Monighetti, C.; Campbell, C. L. Small RNA Profiling of Dengue Virus-Mosquito Interactions Implicates the PIWI RNA Pathway in Anti-Viral Defense BMC Microbiol. 2011, 11, 45 DOI: 10.1186/1471-2180-11-45
  2
  Small RNA profiling of Dengue virus-mosquito interactions implicates the PIWI RNA pathway in anti-viral defense
  Hess, Ann M.; Prasad, Abhishek N.; Ptitsyn, Andrey; Ebel, Gregory D.; Olson, Ken E.; Barbacioru, Catalin; Monighetti, Cinna; Campbell, Corey L.
  BMC Microbiology (2011), 11 (), 45CODEN: BMMIBC; ISSN:1471-2180. (BioMed Central Ltd.)
  Background: Small RNA (sRNA) regulatory pathways (SRRPs) are important to anti-viral defense in mosquitoes. To identify crit. features of the virus infection process in Dengue serotype 2 (DENV2)-infected Ae. aegypti, the authors deep-sequenced small non-coding RNAs. Triplicate biol. replicates were used so that rigorous statistical metrics could be applied. Results: In addn. to virus-derived siRNAs (20-23nts) previously reported for other arbovirus-infected mosquitoes, PIWI pathway sRNAs (piRNAs) (24-30nts) and unusually small RNAs (usRNAs) (13-19nts) were produced in DENV-infected mosquitoes. A major catalytic enzyme of the siRNA pathway, Argonaute 2 (Ago2), co-migrates with a 1 megadalton complex in adults prior to bloodfeeding. SRNAs were cloned and sequenced from Ago2 immunopptns. Viral sRNA patterns change over infection. Host sRNAs were mapped to the published aedine transcriptome and subjected to anal. using edgeR (Bioconductor). SRNA profiles are altered early in DENV2 infection, and mRNA targets from mitochondrial, transcription/translation, and transport functional categories are affected. Moreover, small non-coding RNAs (ncRNAs), such as tRNAs, spliceosomal U RNAs, and snoRNAs are highly enriched in DENV-infected samples at 2 and 4 dpi. Conclusions: These data implicate the PIWI pathway in anti-viral defense. Changes to host sRNA profiles indicate that specific cellular processes are affected during DENV infection, such as mitochondrial function and ncRNA levels. Together, these data provide important progress in understanding the DENV2 infection process in Ae. aegypti.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXjt1Khtbo%253D&md5=3e63ac4e618509bb0a3b14f61690a157
3. 3
  Lopez, J. P.; Diallo, A.; Cruceanu, C.; Fiori, L. M.; Laboissiere, S.; Guillet, I.; Fontaine, J.; Ragoussis, J.; Benes, V.; Turecki, G.; Ernst, C. Biomarker Discovery: Quantification of microRNAs and Other Small Non-Coding RNAs Using next Generation Sequencing BMC Med. Genomics 2015, 8, 35 DOI: 10.1186/s12920-015-0109-x
  3
  Biomarker discovery: quantification of microRNAs and other small non-coding RNAs using next generation sequencing
  Lopez Juan Pablo; Diallo Alpha; Cruceanu Cristiana; Fiori Laura M; Turecki Gustavo; Ernst Carl; Lopez Juan Pablo; Cruceanu Cristiana; Ragoussis Jiannis; Turecki Gustavo; Ernst Carl; Laboissiere Sylvie; Guillet Isabelle; Fontaine Joelle; Ragoussis Jiannis; Benes Vladimir
  BMC medical genomics (2015), 8 (), 35 ISSN:.
  BACKGROUND: Small ncRNAs (sncRNAs) offer great hope as biomarkers of disease and response to treatment. This has been highlighted in the context of several medical conditions such as cancer, liver disease, cardiovascular disease, and central nervous system disorders, among many others. Here we assessed several steps involved in the development of an ncRNA biomarker discovery pipeline, ranging from sample preparation to bioinformatic processing of small RNA sequencing data. METHODS: A total of 45 biological samples were included in the present study. All libraries were prepared using the Illumina TruSeq Small RNA protocol and sequenced using the HiSeq2500 or MiSeq Illumina sequencers. Small RNA sequencing data was validated using qRT-PCR. At each stage, we evaluated the pros and cons of different techniques that may be suitable for different experimental designs. Evaluation methods included quality of data output in relation to hands-on laboratory time, cost, and efficiency of processing. RESULTS: Our results show that good quality sequencing libraries can be prepared from small amounts of total RNA and that varying degradation levels in the samples do not have a significant effect on the overall quantification of sncRNAs via NGS. In addition, we describe the strengths and limitations of three commercially available library preparation methods: (1) Novex TBE PAGE gel; (2) Pippin Prep automated gel system; and (3) AMPure XP beads. We describe our bioinformatics pipeline, provide recommendations for sequencing coverage, and describe in detail the expression and distribution of all sncRNAs in four human tissues: whole-blood, brain, heart and liver. CONCLUSIONS: Ultimately this study provides tools and outcome metrics that will aid researchers and clinicians in choosing an appropriate and effective high-throughput sequencing quantification method for various study designs, and overall generating valuable information that can contribute to our understanding of small ncRNAs as potential biomarkers and mediators of biological functions and disease.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2MbptFCitA%253D%253D&md5=8daa76441523d6c5a5237aefa64cdc13
4. 4
  Gilad, S.; Meiri, E.; Yogev, Y.; Benjamin, S.; Lebanony, D.; Yerushalmi, N.; Kushnir, M.; Cholakh, H.; Melamed, N.; Bentwich, Z.; Hod, M.; Goren, Y.; Chajut, A. Serum MicroRNAs Are Promising Novel Biomarkers PLoS One 2008, 3e3148 DOI: 10.1371/journal.pone.0003148
  There is no corresponding record for this reference.
5. 5
  Calin, G. A.; Croce, C. M. MicroRNA Signatures in Human Cancers Nat. Rev. Cancer 2006, 6, 857– 866 DOI: 10.1038/nrc1997
  5
  MicroRNA signatures in human cancers
  Calin, George A.; Croce, Carlo M.
  Nature Reviews Cancer (2006), 6 (11), 857-866CODEN: NRCAC4; ISSN:1474-175X. (Nature Publishing Group)
  A review. MicroRNA (miRNA) alterations are involved in the initiation and progression of human cancer. The causes of the widespread differential expression of miRNA genes in malignant compared with normal cells can be explained by the location of these genes in cancer-assocd. genomic regions, by epigenetic mechanisms and by alterations in the miRNA processing machinery. MiRNA-expression profiling of human tumors has identified signatures assocd. with diagnosis, staging, progression, prognosis and response to treatment. In addn., profiling has been exploited to identify miRNA genes that might represent downstream targets of activated oncogenic pathways, or that target protein-coding genes involved in cancer.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XhtFWhs7fM&md5=3e20b58432ef9509e227fb1396e0ee15
6. 6
  Flemming, A. Targeting miRNA Pathology in Heart Disease Nat. Rev. Drug Discovery 2014, 13, 336 DOI: 10.1038/nrd4311
  There is no corresponding record for this reference.
7. 7
  Munshi, S. U.; Panda, H.; Holla, P.; Rewari, B. B.; Jameel, S. MicroRNA-150 Is a Potential Biomarker of HIV/AIDS Disease Progression and Therapy PLoS One 2014, 9e95920 DOI: 10.1371/journal.pone.0095920
  There is no corresponding record for this reference.
8. 8
  Liang, H.; Zhou, Z.; Zhang, S.; Zen, K.; Chen, X.; Zhang, C. Identification of Ebola Virus microRNAs and Their Putative Pathological Function Sci. China: Life Sci. 2014, 57, 973– 981 DOI: 10.1007/s11427-014-4759-2
  8
  Identification of Ebola virus microRNAs and their putative pathological function
  Liang, HongWei; Zhou, Zhen; Zhang, SuYang; Zen, Ke; Chen, Xi; Zhang, ChenYu
  Science China: Life Sciences (2014), 57 (10), 973-981CODEN: SCLSCJ; ISSN:1674-7305. (Science China Press)
  Ebola virus (EBOV), a member of the filovirus family, is an enveloped neg.-sense RNA virus that causes lethal infections in humans and primates. Recently, >1000 people have been killed by the Ebola virus disease in Africa, yet no specific treatment or diagnostic tests for EBOV are available. The authors identified two putative viral microRNA precursors (pre-miRNAs) and three putative mature microRNAs (miRNAs) derived from the EBOV genome. The prodn. of the EBOV miRNAs was further validated in HEK293T cells transfected with a pcDNA6.2-GW/EmGFP-EBOV-pre-miRNA plasmid, indicating that EBOV miRNAs can be produced through the cellular miRNA processing machinery. The authors also predicted the potential target genes of these EBOV miRNAs and their possible biol. functions. Overall, this study reports for the first time that EBOV may produce miRNAs, which could serve as non-invasive biomarkers for the diagnosis and prognosis of EBOV infection and as therapeutic targets for Ebola viral infection treatment.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhslSrsbnL&md5=19032eb8699c8371efc2351fd7092197
9. 9
  Hong, Y.; Wang, C.; Fu, Z.; Liang, H.; Zhang, S.; Lu, M.; Sun, W.; Ye, C.; Zhang, C. Y.; Zen, K.; Shi, L.; Zhang, C.; Chen, X. Systematic Characterization of Seminal Plasma piRNAs as Molecular Biomarkers for Male Infertility Sci. Rep. 2016, 624229 DOI: 10.1038/srep24229
  9
  Systematic characterization of seminal plasma piRNAs as molecular biomarkers for male infertility
  Hong, Yeting; Wang, Cheng; Fu, Zheng; Liang, Hongwei; Zhang, Suyang; Lu, Meiling; Sun, Wu; Ye, Chao; Zhang, Chen-Yu; Zen, Ke; Shi, Liang; Zhang, Chunni; Chen, Xi
  Scientific Reports (2016), 6 (), 24229CODEN: SRCEC3; ISSN:2045-2322. (Nature Publishing Group)
  Although piwi-interacting RNAs (piRNAs) play pivotal roles in spermatogenesis, little is known about piRNAs in the seminal plasma of infertile males. In this study, we systematically investigated the profiles of seminal plasma piRNAs in infertile males to identify piRNAs that are altered during infertility and evaluate their diagnostic value. Seminal plasma samples were obtained from 211 infertile patients (asthenozoospermia and azoospermia) and 91 fertile controls. High-throughput sequencing technol. was employed to screen piRNA profiles in seminal plasma samples pooled from healthy controls and infertile patients. The results identified 61 markedly altered piRNAs in infertile patient groups compared with control group. Next, a quant. RT-PCR assay was conducted in the training and validation sets to measure and confirm the concns. of altered piRNAs. The results identified a panel of 5 piRNAs that were significantly decreased in seminal plasma of infertile patients compared with healthy controls. ROC curve anal. and risk score anal. revealed that the diagnostic potential of these 5 piRNAs to distinguish asthenozoospermic and azoospermic individuals from healthy controls was high. In summary, this study identifies a panel of piRNAs that can accurately distinguish fertile from infertile males. This finding may provide pathophysiol. clues about the development of infertility.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XmtVKju7s%253D&md5=aafa4784167ba4ef48b4b0024a5770de
10. 10
  Morazzani, E. M.; Wiley, M. R.; Murreddu, M. G.; Adelman, Z. N.; Myles, K. M. Production of Virus-Derived Ping-Pong-Dependent piRNA-like Small RNAs in the Mosquito Soma PLoS Pathog. 2012, 8e1002470 DOI: 10.1371/journal.ppat.1002470
  There is no corresponding record for this reference.
11. 11
  Alonso-Cristobal, P.; Vilela, P.; El-Sagheer, A.; Lopez-Cabarcos, E.; Brown, T.; Muskens, O. L.; Rubio-Retama, J.; Kanaras, A. G. Highly Sensitive DNA Sensor Based on Upconversion Nanoparticles and Graphene Oxide ACS Appl. Mater. Interfaces 2015, 7, 12422– 12429 DOI: 10.1021/am507591u
  11
  Highly Sensitive DNA Sensor Based on Upconversion Nanoparticles and Graphene Oxide
  Alonso-Cristobal, P.; Vilela, P.; El-Sagheer, A.; Lopez-Cabarcos, E.; Brown, T.; Muskens, O. L.; Rubio-Retama, J.; Kanaras, A. G.
  ACS Applied Materials & Interfaces (2015), 7 (23), 12422-12429CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)
  In this work we demonstrate a DNA biosensor based on fluorescence resonance energy transfer (FRET) between NaYF4:Yb,Er nanoparticles and graphene oxide (GO). Monodisperse NaYF4:Yb,Er nanoparticles with a mean diam. of 29.1 ± 2.2 nm were synthesized and coated with a SiO2 shell of 11 nm, which allowed the attachment of single strands of DNA. When these DNA-functionalized NaYF4:Yb,Er@SiO2 nanoparticles were in the proximity of the GO surface, the π-π stacking interaction between the nucleobases of the DNA and the sp2 carbons of the GO induced a FRET fluorescence quenching due to the overlap of the fluorescence emission of the NaYF4:Yb,Er@SiO2 and the absorption spectrum of GO. By contrast, in the presence of the complementary DNA strands, the hybridization leads to double-stranded DNA that does not interact with the GO surface, and thus the NaYF4:Yb,Er@SiO2 nanoparticles remain unquenched and fluorescent. The high sensitivity and specificity of this sensor introduces a new method for the detection of DNA with a detection limit of 5 pM.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsF2ht7w%253D&md5=d4dc92c0e83a786d31ddeadaf28495ac
12. 12
  Laurenti, M.; Paez-Perez, M.; Algarra, M.; Alonso-Cristobal, P.; Lopez-Cabarcos, E.; Mendez-Gonzalez, D.; Rubio-Retama, J. Enhancement of the Upconversion Emission by Visible-to-Near-Infrared Fluorescent Graphene Quantum Dots for miRNA Detection ACS Appl. Mater. Interfaces 2016, 8, 12644– 12651 DOI: 10.1021/acsami.6b02361
  12
  Enhancement of the Upconversion Emission by Visible-to-Near-Infrared Fluorescent Graphene Quantum Dots for miRNA Detection
  Laurenti, Marco; Paez-Perez, Miguel; Algarra, Manuel; Alonso-Cristobal, Paulino; Lopez-Cabarcos, Enrique; Mendez-Gonzalez, Diego; Rubio-Retama, Jorge
  ACS Applied Materials & Interfaces (2016), 8 (20), 12644-12651CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)
  We developed a sensor for the detection of specific microRNA (miRNA) sequences that was based on graphene quantum dots (GQDs) and ssDNA-UCNP@SiO2. The proposed sensor exploits the interaction between the sp2 carbon atoms of the GQD, mainly π-π stacking, and the DNA nucleobases anchored on the upconversion nanoparticles (UCNPs). This interaction brings the GQD to the surface of the ssDNA-UCNP@SiO2 system, enhancing the upconversion emission. On the other hand, hybridization of the single-stranded DNA (ssDNA) chains anchored on the nanoparticles with their complementary miRNA sequences blocks the capacity of the UCNPs to interact with the GQD through π-π stacking. That gives as result a redn. of the fluorescent enhancement, which is dependent on the concn. of miRNA sequences. This effect was used to create a sensor for miRNA sequences with a detection limit of 10 fM.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XnsVWitbs%253D&md5=440d7d6c6e331bac6a7bd2365d2de75d
13. 13
  Yang, X.; Yu, Y.; Gao, Z. A Highly Sensitive Plasmonic DNA Assay Based on Triangular Silver Nanoprism Etching ACS Nano 2014, 8, 4902– 4907 DOI: 10.1021/nn5008786
  13
  A Highly Sensitive Plasmonic DNA Assay Based on Triangular Silver Nanoprism Etching
  Yang, Xinjian; Yu, Yuebo; Gao, Zhiqiang
  ACS Nano (2014), 8 (5), 4902-4907CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)
  Specific nucleic acid detection by using simple and low-cost assays is important in clin. diagnostics, mutation detection, and biodefense applications. Most current methods for the quantification of low concns. of DNA require costly and sophisticated instruments. Here, the authors have developed a facile DNA detection platform based on a plasmonic triangular silver nanoprism etching process, in which the shape and size of the nanoprisms were altered accompanied by a substantial surface plasmon resonance shift. Through the combination of enzyme-linked hybridization chain reaction amplification and inherent sensitivity of plasmonic silver nanoprisms, this assay could detect as low as 6.0 fM target DNA. Considering the high sensitivity and selectivity of this plasmonic DNA assay, it is expected to be of great interest in clin. diagnostics.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXmvFCjurc%253D&md5=a850a5eaf83c924d47304b5ba2bfb124
14. 14
  Tang, L.; Chun, I. S.; Wang, Z.; Li, J.; Li, X.; Lu, Y. DNA Detection Using Plasmonic Enhanced near-Infrared Photoluminescence of Gallium Arsenide Anal. Chem. 2013, 85, 9522– 9527 DOI: 10.1021/ac401169c
  14
  DNA Detection Using Plasmonic Enhanced Near-Infrared Photoluminescence of Gallium Arsenide
  Tang, Longhua; Chun, Ik Su; Wang, Zidong; Li, Jinghong; Li, Xiuling; Lu, Yi
  Analytical Chemistry (Washington, DC, United States) (2013), 85 (20), 9522-9527CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)
  Efficient near-IR detection of specific DNA with single nucleotide polymorphism selectivity is important for diagnostics and biomedical research. Herein, we report the use of gallium arsenide (GaAs) as a sensing platform for probing DNA immobilization and targeting DNA hybridization, resulting in ∼8-fold enhanced GaAs photoluminescence (PL) at ∼875 nm. The new signal amplification strategy, further coupled with the plasmonic effect of Au nanoparticles, is capable of detecting DNA mols. with a detection limit of 0.8 pM and selectivity against single base mismatches. Such an ultrasensitive near-IR sensor can find a wide range of biochem. and biomedical applications.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtlKktL3I&md5=e148ba21c812ac08bcff44370080f5f1
15. 15
  Tsang, M.-K.; Ye, W.; Wang, G.; Li, J.; Yang, M.; Hao, J. Ultrasensitive Detection of Ebola Virus Oligonucleotide Based on Upconversion Nanoprobe/Nanoporous Membrane System ACS Nano 2016, 10, 598– 605 DOI: 10.1021/acsnano.5b05622
  15
  Ultrasensitive Detection of Ebola Virus Oligonucleotide Based on Upconversion Nanoprobe/Nanoporous Membrane System
  Tsang, Ming-Kiu; Ye, WeiWei; Wang, Guojing; Li, Jingming; Yang, Mo; Hao, Jianhua
  ACS Nano (2016), 10 (1), 598-605CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)
  Ebola outbreaks are currently of great concern, and therefore, development of effective diagnosis methods is urgently needed. The key for lethal virus detection is high sensitivity, since early-stage detection of virus may increase the probability of survival. Here, we propose a luminescence scheme of assay consisting of BaGdF5:Yb/Er upconversion nanoparticles (UCNPs) conjugated with oligonucleotide probe and gold nanoparticles (AuNPs) linked with target Ebola virus oligonucleotide. As a proof of concept, a homogeneous assay was fabricated and tested, yielding a detection limit at picomolar level. The luminescence resonance energy transfer is ascribed to the spectral overlapping of upconversion luminescence and the absorption characteristics of AuNPs. Moreover, we anchored the UCNPs and AuNPs on a nanoporous alumina (NAAO) membrane to form a heterogeneous assay. Importantly, the detection limit was greatly improved, exhibiting a remarkable value at the femtomolar level. The enhancement is attributed to the increased light-matter interaction throughout the nanopore walls of the NAAO membrane. The specificity test suggested that the nanoprobes were specific to Ebola virus oligonucleotides. The strategy combining UCNPs, AuNPs, and NAAO membrane provides new insight into low-cost, rapid, and ultrasensitive detection of different diseases. Furthermore, we explored the feasibility of clin. application by using inactivated Ebola virus samples. The detection results showed great potential of our heterogeneous design for practical application.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtlSktw%253D%253D&md5=4d7221463dd314bbf3c1a937c1449c88
16. 16
  Chen, Z.; Chen, H.; Hu, H.; Yu, M.; Li, F.; Zhang, Q.; Zhou, Z.; Yi, T.; Huang, C. Versatile Synthesis Strategy for Carboxylic Acid-Functionalized Upconverting Nanophosphors as Biological Labels J. Am. Chem. Soc. 2008, 130, 3023– 3029 DOI: 10.1021/ja076151k
  16
  Versatile Synthesis Strategy for Carboxylic Acid-functionalized Upconverting Nanophosphors as Biological Labels
  Chen, Zhigang; Chen, Huili; Hu, He; Yu, Mengxiao; Li, Fuyou; Zhang, Qiang; Zhou, Zhiguo; Yi, Tao; Huang, Chunhui
  Journal of the American Chemical Society (2008), 130 (10), 3023-3029CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  Up-converting rare-earth nanophosphors (UCNPs) have great potential to revolutionize biol. luminescent labels, but their use has been limited by difficulties in obtaining UCNPs that are biocompatible. To address this problem, the authors have developed a simple and versatile strategy for converting hydrophobic UCNPs into water-sol. and carboxylic acid-functionalized analogs by directly oxidizing oleic acid ligands with the Lemieux-von Rudloff reagent. This oxidn. process has no obvious adverse effects on the morphologies, phases, compns. and luminescent capabilities of UCNPs. Furthermore, as revealed by Fourier transform IR (FTIR) and NMR results, oleic acid ligands on the surface of UCNPs can be oxidized into azelaic acids (HOOC(CH2)7COOH), which results in the generation of free carboxylic acid groups on the surface. The presence of free carboxylic acid groups not only confers high soly. in water, but also allows further conjugation with biomols. such as streptavidin. A highly sensitive DNA sensor based on such streptavidin-coupled UCNPs have been prepd., and the demonstrated results suggest that these biocompatible UCNPs have great superiority as luminescent labeling materials for biol. applications.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXitVamt7w%253D&md5=882ec4da9fa107bff39cf7f4939c22ea
17. 17
  Ma, W.; Kuang, H.; Xu, L.; Ding, L.; Xu, C.; Wang, L.; Kotov, N. A. Attomolar DNA Detection with Chiral Nanorod Assemblies Nat. Commun. 2013, 42689 DOI: 10.1038/ncomms3689
  17
  Attomolar DNA detection with chiral nanorod assemblies
  Ma Wei; Kuang Hua; Xu Liguang; Ding Li; Xu Chuanlai; Wang Libing; Kotov Nicholas A
  Nature communications (2013), 4 (), 2689 ISSN:.
  Nanoscale plasmonic assemblies display exceptionally strong chiral optical activity. So far, their structural design was primarily driven by challenges related to metamaterials whose practical applications are remote. Here we demonstrate that gold nanorods assembled by the polymerase chain reaction into DNA-bridged chiral systems have promising analytical applications. The chiroplasmonic activity of side-by-side assembled patterns is attributed to a 7-9 degree twist between the nanorod axes. This results in a strong polarization rotation that matches theoretical expectations. The amplitude of the bisignate 'wave' in the circular dichroism spectra of side-by-side assemblies demonstrates excellent linearity with the amount of target DNA. The limit of detection for DNA using side-by-side assemblies is as low as 3.7 aM. This chiroplasmonic method may be particularly useful for biological analytes larger than 2-5 nm which are difficult to detect by methods based on plasmon coupling and 'hot spots'. Circular polarization increases for inter-nanorod gaps between 2 and 20 nm when plasmonic coupling rapidly decreases. Reaching the attomolar limit of detection for simple and reliable bioanalysis of oligonucleotides may have a crucial role in DNA biomarker detection for early diagnostics of different diseases, forensics and environmental monitoring.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2c7gt1Smsg%253D%253D&md5=1d0e5d950288b44286c90ae70a182060
18. 18
  Li, S.; Xu, L.; Ma, W.; Wu, X.; Sun, M.; Kuang, H.; Wang, L.; Kotov, N. A.; Xu, C. Dual-Mode Ultrasensitive Quantification of MicroRNA in Living Cells by Chiroplasmonic Nanopyramids Self-Assembled from Gold and Upconversion Nanoparticles J. Am. Chem. Soc. 2016, 138, 306– 312 DOI: 10.1021/jacs.5b10309
  18
  Dual-mode ultrasensitive quantification of microRNA in living cells by chiroplasmonic nanopyramids self-assembled from gold and upconversion nanoparticles
  Li, Si; Xu, Liguang; Ma, Wei; Wu, Xiaoling; Sun, Maozhong; Kuang, Hua; Wang, Libing; Kotov, Nicholas A.; Xu, Chuanlai
  Journal of the American Chemical Society (2016), 138 (1), 306-312CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)
  Chiral self-assembled nanomaterials with biol. applications have attracted great interest. In this study, DNA-driven gold-upconversion nanoparticle (Au-UCNP) pyramids were fabricated to detect intracellular microRNA (miRNA) in real time. The Au-UCNP pyramids are doubly optically active, displaying strong plasmonic CD at 521 nm and significant luminescence in 500-600 nm, and therefore can be monitored by both of them. CD will decrease while the luminescence intensity increases in the presence of miRNA. The exptl. results show that the CD intensity had an outstanding linear range from 0.073 to 43.65 fmol/10 μgRNA and a limit of detection (LOD) of 0.03 fmol/10 μgRNA, whereas the luminescence intensity ranged from 0.16 to 43.65 fmol/10 μgRNA with a LOD of 0.12 fmol/10 μgRNA. These data indicate that the CD signal is much more sensitive to the concn. of miRNA than the luminescent signal, which is attributed to the strong CD intensity arising from the spin angular momentum of the photon interaction with chiral nanostructures and the plasmonic enhancement of the intrinsic chirality of DNA mols. in the pyramids. This approach opens up a new avenue to the ultrasensitive detection and quantification of miRNA in living cells.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXitVGrsr7F&md5=e389f8dfe701386660fff8d81b3e6537
19. 19
  Wang, F.; Liu, X. Recent Advances in the Chemistry of Lanthanide-Doped Upconversion Nanocrystals Chem. Soc. Rev. 2009, 38, 976– 989 DOI: 10.1039/b809132n
  19
  Recent advances in the chemistry of lanthanide-doped upconversion nanocrystals
  Wang, Feng; Liu, Xiaogang
  Chemical Society Reviews (2009), 38 (4), 976-989CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)
  A review. Lanthanide ions exhibit unique luminescent properties, including the ability to convert near IR long-wavelength excitation radiation into shorter visible wavelengths through a process known as photon upconversion. In recent years lanthanide-doped upconversion nanocrystals were developed as a new class of luminescent optical labels that have become promising alternatives to org. fluorophores and quantum dots for applications in biol. assays and medical imaging. These techniques offer low autofluorescence background, large anti-Stokes shifts, sharp emission bandwidths, high resistance to photobleaching, and high penetration depth and temporal resoln. Such techniques also show potential for improving the selectivity and sensitivity of conventional methods. They also pave the way for high throughput screening and miniaturization. This tutorial review focuses on the recent development of various synthetic approaches and possibilities for chem. tuning of upconversion properties, as well as giving an overview of biol. applications of these luminescent nanocrystals.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXjsFaisr4%253D&md5=6a5e2b96c141b9c8191bf9a6e139a15b
20. 20
  Liu, C.; Wang, H.; Li, X.; Chen, D. Monodisperse, Size-Tunable and Highly Efficient β-NaYF4:Yb,Er(Tm) up-Conversion Luminescent Nanospheres: Controllable Synthesis and Their Surface Modifications J. Mater. Chem. 2009, 19, 3546– 3553 DOI: 10.1039/b820254k
  20
  Monodisperse, size-tunable and highly efficient β-NaYF4:Yb,Er(Tm) up-conversion luminescent nanospheres: controllable synthesis and their surface modifications
  Liu, Chenghui; Wang, Hui; Li, Xiao; Chen, Depu
  Journal of Materials Chemistry (2009), 19 (21), 3546-3553CODEN: JMACEP; ISSN:0959-9428. (Royal Society of Chemistry)
  Monodisperse, oil-dispersible β-NaYF4:Yb,Er(Tm) up-conversion (UC) luminescent nanospheres (NPs) were successfully synthesized. The as-prepd. NPs show high size-uniformity without any size-selection process, and the sizes of the NPs can be tuned in 18-45 nm, which are well suitable for biolabels. The NPs are thoroughly characterized and a growth mechanism is proposed. By co-doping Yb-Er or Yb-Tm, the as-prepd. NPs can show bright green or blue UC luminescence under the irradn. of a 980. nm near-IR (NIR) laser, and the UC luminescence can be obviously enhanced by constructing a NaYF4:Yb,Er@NaYF4 core/shell structure. Also, the hydrophobic UC nanospheres (UCNPs) are converted into H2O-sol. by a robust ligand-exchange pathway with poly(acrylic acid). The presence of free carboxylic acid groups on their surfaces not only results in high soly. in H2O, but also allows further conjugation with biomols. such as antigens, antibodies and oligonucleotides, which pave the way for potential bio-applications of the UCNPs.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXmtFCjsr0%253D&md5=eb45d95fe7fa741f5f371bb444bb84d6
21. 21
  Liu, B.; Chen, Y.; Li, C.; He, F.; Hou, Z.; Huang, S.; Zhu, H.; Chen, X.; Lin, J. Poly(Acrylic Acid) Modification of Nd³⁺ -Sensitized Upconversion Nanophosphors for Highly Efficient UCL Imaging and pH-Responsive Drug Delivery Adv. Funct. Mater. 2015, 25, 4717– 4729 DOI: 10.1002/adfm.201501582
  There is no corresponding record for this reference.
22. 22
  Zhang, C.; Yuan, Y.; Zhang, S.; Wang, Y.; Liu, Z. Biosensing Platform Based on Fluorescence Resonance Energy Transfer from Upconverting Nanocrystals to Graphene Oxide Angew. Chem., Int. Ed. Engl. 2011, 50, 6851– 6854 DOI: 10.1002/anie.201100769
  There is no corresponding record for this reference.
23. 23
  Wu, S.; Duan, N.; Ma, X.; Xia, Y.; Wang, H.; Wang, Z.; Zhang, Q. Multiplexed Fluorescence Resonance Energy Transfer Aptasensor between Upconversion Nanoparticles and Graphene Oxide for the Simultaneous Determination of Mycotoxins Anal. Chem. 2012, 84, 6263– 6270 DOI: 10.1021/ac301534w
  23
  Multiplexed Fluorescence Resonance Energy Transfer Aptasensor between Upconversion Nanoparticles and Graphene Oxide for the Simultaneous Determination of Mycotoxins
  Wu, Shijia; Duan, Nuo; Ma, Xiaoyuan; Xia, Yu; Wang, Hongxin; Wang, Zhouping; Zhang, Qian
  Analytical Chemistry (Washington, DC, United States) (2012), 84 (14), 6263-6270CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)
  We presented a new aptasensor for mycotoxins, which was based on multiplexed fluorescence resonance energy transfer (FRET) between multicolor upconversion fluorescent nanoparticles (UCNPs) as donors and graphene oxide (GO) as the entire and effective acceptor. BaY0.78F5:Yb0.2,Er0.02 and BaY0.78F5:Yb0.7,Tm0.02 upconversion nanoparticles were synthesized and functionalized, resp., with immobilized ochratoxin A (OTA)-aptamers and fumonisin B1 (FB1)-aptamers. On the basis of the strong π-π stacking effect between the nucleobases of the aptamers and the sp2 atoms of GO, the aptamer modified-UCNPs can be brought in close proximity to the GO surface. The strong upconversion fluorescence both of BaY0.78F5:Yb0.2, Er0.02 and BaY0.78F5:Yb0.2, Tm0.02 can be completely quenched by the GO, because of a good overlap between the fluorescence emission of multicolor UCNPs and the absorption spectrum of GO. In contrast, in the presence of OTA and FB1, the aptamers preferred to bind to their corresponding mycotoxins, which led to changes in the formation of aptamers, and therefore, aptamer modified-UCNPs were far away from the GO surface. Our study results showed that the fluorescence intensity of BaYF5:Yb Er and BaYF5:Yb Tm were related to the concn. of OTA and FB1. We therefore developed a sensitive and simple platform for the simultaneous detection of OTA and FB1 with multicolor UCNPs and GO as the FRET pair. The aptasensor provided a linear range from 0.05 to 100 ng·mL-1 for OTA and 0.1 to 500 ng·mL-1 for FB1; the detection limit of OTA was 0.02 ng·mL-1 and FB1 was 0.1 ng·mL-1. As a practical application, the aptasensor was used to monitor OTA and FB1 level in naturally contaminated maize samples with the results consistent with that of a classic ELISA method. More importantly, the novel multiplexed FRET was established for the first time based on multiplexed energy donors to the entire energy acceptor; this work was expected to open up a new field of FRET system applications for various targets.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XptFSqt74%253D&md5=8de949b0a57d38397bd208e0b3233a77
24. 24
  Sedlmeier, A.; Gorris, H. H. Surface Modification and Characterization of Photon-Upconverting Nanoparticles for Bioanalytical Applications Chem. Soc. Rev. 2015, 44, 1526– 1560 DOI: 10.1039/C4CS00186A
  24
  Surface modification and characterization of photon-upconverting nanoparticles for bioanalytical applications
  Sedlmeier, Andreas; Gorris, Hans H.
  Chemical Society Reviews (2015), 44 (6), 1526-1560CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)
  A review. Photon-upconverting nanoparticles (UCNPs) can be excited by near-IR light and emit visible light (anti-Stokes emission) which prevents autofluorescence and light scattering of biol. samples. The potential for background-free imaging has attracted wide interest in UCNPs in recent years. Small and homogeneous lanthanide-doped UCNPs that display high upconversion efficiency have typically been synthesized in org. solvents. Bioanal. applications, however, require a subsequent phase transfer to aq. solns. Hence, the surface properties of UCNPs must be well designed and characterized to grant both a stable aq. colloidal dispersion and the ability to conjugate biomols. and other ligands on the nanoparticle surface. In this review, we introduce various routes for the surface modification of UCNPs and critically discuss their advantages and disadvantages. The last part covers various anal. methods that enable a thorough examn. of the progress and success of the surface functionalization.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsVGjur7K&md5=103ff17432cb75c8fa71ea384111f65e
25. 25
  Doughan, S.; Han, Y.; Uddayasankar, U.; Krull, U. J. Solid-Phase Covalent Immobilization of Upconverting Nanoparticles for Biosensing by Luminescence Resonance Energy Transfer ACS Appl. Mater. Interfaces 2014, 6, 14061– 14068 DOI: 10.1021/am503391m
  25
  Solid-Phase Covalent Immobilization of Upconverting Nanoparticles for Biosensing by Luminescence Resonance Energy Transfer
  Doughan, Samer; Han, Yi; Uddayasankar, Uvaraj; Krull, Ulrich J.
  ACS Applied Materials & Interfaces (2014), 6 (16), 14061-14068CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)
  Monodisperse water-sol. upconverting nanoparticles (UCNPs) were immobilized onto modified glass substrates for development of biosensing surfaces that operated using luminescence resonance energy transfer (LRET). Amine modified UCNPs were prepd. from oleic acid capped UCNPs by ligand exchange using o-phosphorylethanolamine (PEA). PEA-UCNPs were covalently immobilized on aldehyde functionalized coverslips. Environmental SEM (ESEM) images indicated a homogeneous distribution of UCNPs on surfaces with a high immobilization d. of approx. 1.3 × 1011 UCNP cm-2. This is the first account of covalent immobilization of UCNPs for bioassay and biosensor development where the d. is on par with the high immobilization densities reported for other types of nanoparticles. The functionality and stability of the immobilized NPs were demonstrated by examg. an LRET-based bioassay. The well-known sandwich assay for the detection of thrombin was selected as a model in which UCNPs were used as donors and quantum dots (QDs) as acceptors. The closely packed UCNPs on the glass surface showed a 2.5-fold enhancement in assay sensitivity compared to less-densely packed surfaces. In addn., a 1.5-fold enhancement in energy transfer efficiency was shown for solid-phase compared to soln.-phase LRET.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtFOqtbrO&md5=f3bf8690004507e37459b076003cc3d8
26. 26
  Sedlmeier, A.; Hlavek, A.; Birner, L.; Mickert, M. J.; Muhr, V.; Hirsch, T.; Corstjens, P. L. A. M.; Tanke, H. J.; Soukka, T.; Gorris, H. H. Highly Sensitive Laser Scanning of Photon-Upconverting Nanoparticles on a Macroscopic Scale Anal. Chem. 2016, 88, 1835– 1841 DOI: 10.1021/acs.analchem.5b04147
  26
  Highly Sensitive Laser Scanning of Photon-Upconverting Nanoparticles on a Macroscopic Scale
  Sedlmeier, Andreas; Hlavacek, Antonin; Birner, Lucia; Mickert, Matthias J.; Muhr, Verena; Hirsch, Thomas; Corstjens, Paul L. A. M.; Tanke, Hans J.; Soukka, Tero; Gorris, Hans H.
  Analytical Chemistry (Washington, DC, United States) (2016), 88 (3), 1835-1841CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)
  An upconversion laser scanner has been optimized to exploit the advantages of photon-upconverting nanoparticles (UCNPs) for background-free imaging on a macroscopic scale. A collimated 980 nm laser beam afforded high local excitation densities to account for the nonlinear luminescence response of UCNPs. As few as 2000 nanoparticles were detectable, and the linear dynamic range covered more than 5 orders of magnitude, which is essentially impossible by using conventional fluorescent dyes. UCNPs covered by a dye-doped silica shell were sepd. by agarose gel electrophoresis and scanned by a conventional fluorescence scanner as well as the upconversion scanner. Both optical labels could be detected independently. Finally, upconversion images of lateral flow test strips were recorded to facilitate the sensitive and quant. detection of disease markers. A marker for the parasitic worm Schistosoma was used in this study.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXitV2nsbzK&md5=abbab3239a2114b4d7bb3bd9c09bc27b
27. 27
  Kale, V.; Päkkilä, H.; Vainio, J.; Ahomaa, A.; Sirkka, N.; Lyytikäinen, A.; Talha, S. M.; Kutsaya, A.; Waris, M.; Julkunen, I.; Soukka, T. Spectrally and Spatially Multiplexed Serological Array-in-Well Assay Utilizing Two-Color Upconversion Luminescence Imaging Anal. Chem. 2016, 88, 4470– 4477 DOI: 10.1021/acs.analchem.6b00337
  27
  Spectrally and Spatially Multiplexed Serological Array-in-Well Assay Utilizing Two-Color Upconversion Luminescence Imaging
  Kale, Vishal; Pakkila, Henna; Vainio, Jiri; Ahomaa, Anna; Sirkka, Nina; Lyytikainen, Annika; Talha, Sheikh Mohammad; Kutsaya, Anna; Waris, Matti; Julkunen, Ilkka; Soukka, Tero
  Analytical Chemistry (Washington, DC, United States) (2016), 88 (8), 4470-4477CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)
  We demonstrate a simple dual-mode multiplexed array-in-well immunoassay for simultaneous classification and detection of serum IgG and IgM antibodies against influenza A and human adenoviruses based on the color and position of the upconversion luminescence on the array. Biotinylated influenza A/H1N1 and A/H5N1 as well as adenovirus serotype 2 and 5 hexon antigens along with pos. and neg. controls were printed in an array format onto the bottom of streptavidin-coated microtiter wells. The anti-influenza A and antiadenovirus antibodies present in the sample were captured to the array and detected with antihuman antibody-coated upconverting nanophosphors (UCNPs). The green emitting UCNPs (NaYF4:Yb3+,Er3+) coated with antihuman IgG and blue emitting UCNPs (NaYF4:Yb3+,Tm3+) coated with antihuman IgM were used to detect human IgG and IgM antibodies, resp. The emission of the bound UCNPs was imaged free of autofluorescence with anti-Stokes photoluminescence microwell imager. No spectral cross-talk was obsd. between green and blue emitting UCNPs. Also the cross-reactivities between UCNP-conjugates and immobilized human IgG and IgM antibodies were negligible. Position of the signal on the array defined the antigen specificity and the antibody class was defined by the color of the upconversion luminescence. This technol. could be used for differentiation between acute infection from past infection and immunity. Addnl., the class of the antibody response can be used for the differentiation between primary and secondary infections, hence, facilitating epidemiol. seroprevalence studies.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XksVGrsLY%253D&md5=5c9bce5cfcde3e4e1837fbb85fab8f24
28. 28
  Ylihärsilä, M.; Valta, T.; Karp, M.; Hattara, L.; Harju, E.; Hölsä, J.; Saviranta, P.; Waris, M.; Soukka, T. Oligonucleotide Array-in-Well Platform for Detection and Genotyping Human Adenoviruses by Utilizing Upconverting Phosphor Label Technology Anal. Chem. 2011, 83, 1456– 1461 DOI: 10.1021/ac103155f
  There is no corresponding record for this reference.
29. 29
  van de Rijke, F.; Zijlmans, H.; Li, S.; Vail, T.; Raap, A. K.; Niedbala, R. S.; Tanke, H. J. Up-converting Phosphor Reporters for Nucleic Acid Microarrays Nat. Biotechnol. 2001, 19, 273– 276 DOI: 10.1038/85734
  29
  Up-converting phosphor reporters for nucleic acid microarrays
  van de Rijke, Frans; Zijlmans, Henry; Li, Shang; Vail, Tim; Raap, Anton K.; Niedbala, R. Sam; Tanke, Hans J.
  Nature Biotechnology (2001), 19 (3), 273-276CODEN: NABIF9; ISSN:1087-0156. (Nature America Inc.)
  An important application of robotically spotted DNA microarrays is the monitoring of RNA expression levels. A clear limitation of this technol. is the relatively large amt. of RNA that is required per hybridization as a result of low hybridization efficiency and limiting detection sensitivity provided by conventional fluorescent reporters. We have used a recently introduced luminescent reporter technol., called UPT (up-converting phosphor technol.). Down-converting phosphors have been applied before to detect nucleic acids on filters using time-resolved fluorometry. The unique feature of the phosphor particles (size 0.4 μm) used here is that they emit visible light when illuminated with IR (IR) light (980 nm) as a result of a phenomenon called up-conversion. Because neither support material of microarrays nor biomols. possess up-conversion properties, an enhanced image contrast is expected when these nonfading phosphor particles are applied to detect nucleic acid hybrids on microarrays. Comparison of the UPT reporter to cyanine 5 (Cy5), in a low-complexity model system showed a two order of magnitude linear relationship between phosphor luminescence and target concn. and resulted in an excellent correlation between the two reporter systems for variable target concns. (R2 = 0.95). However, UPT proved to be superior in sensitivity, even though a wide-field microscope equipped with a xenon lamp was used. This higher sensitivity was demonstrated by complementary DNA (cDNA) microarray hybridizations using cDNAs for housekeeping genes as probes and complex cDNA as target. These results suggest that UPT reporter technol. in combination with a dedicated IR laser array-scanner holds significant promise for various microarray applications.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3MXhslejs7g%253D&md5=49aaef5decb0b894d0a6a050a6a6bcb2
30. 30
  Hlaváček, A.; Farka, Z.; Hübner, M.; Horňáková, V.; Němeček, D.; Niessner, R.; Skládal, P.; Knopp, D.; Gorris, H. H. Competitive Upconversion-Linked Immunosorbent Assay for the Sensitive Detection of Diclofenac Anal. Chem. 2016, 88, 6011– 6017 DOI: 10.1021/acs.analchem.6b01083
  30
  Competitive Upconversion-Linked Immunosorbent Assay for the Sensitive Detection of Diclofenac
  Hlavacek, Antonin; Farka, Zdenek; Huebner, Maria; Hornakova, Veronika; Nemecek, Daniel; Niessner, Reinhard; Skladal, Petr; Knopp, Dietmar; Gorris, Hans H.
  Analytical Chemistry (Washington, DC, United States) (2016), 88 (11), 6011-6017CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)
  Photon-upconverting nanoparticles (UCNPs) emit light of shorter wavelength under near-IR excitation and thus avoid optical background interference. We have exploited this unique photophys. feature to establish a sensitive competitive immunoassay for the detection of the pharmaceutical micropollutant diclofenac (DCF) in water. The so-called upconversion-linked immunosorbent assay (ULISA) was critically dependent on the design of the upconversion luminescent detection label. Silica-coated UCNPs (50 nm in diam.) exposing carboxyl groups on the surface were conjugated to a secondary anti-IgG antibody. We investigated the structure and monodispersity of the nanoconjugates in detail. Using a highly affine anti-DCF primary antibody, the optimized ULISA reached a detection limit of 0.05 ng DCF per mL. This performance came close to a conventional ELISA (ELISA) without the need for an enzyme-mediated signal amplification step. The ULISA was further employed for analyzing drinking and surface water samples. The results were were consistent with a conventional ELISA as well as liq. chromatog.-mass spectrometry (LC-MS).
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XnslCru7Y%253D&md5=c13c4d145820a8fd0358805b9af4f11d
31. 31
  El-Sagheer, A. H.; Brown, T. Click Chemistry with DNA Chem. Soc. Rev. 2010, 39, 1388– 1405 DOI: 10.1039/b901971p
  31
  Click chemistry with DNA
  El-Sagheer, Afaf H.; Brown, Tom
  Chemical Society Reviews (2010), 39 (4), 1388-1405CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)
  A review. The advent of click chem. has led to an influx of new ideas in the nucleic acids field. The copper catalyzed alkyne-azide cycloaddn. (CuAAC) reaction is the method of choice for DNA click chem. due to its remarkable efficiency. It was used to label oligonucleotides with fluorescent dyes, sugars, peptides and other reporter groups, to cyclize DNA, to synthesize DNA catenanes, to join oligonucleotides to PNA, and to produce analogs of DNA with modified nucleobases and backbones. In this crit. review the authors describe some of the pioneering work that was carried out in this area (78 refs.).
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXjs1Ggtbk%253D&md5=686633602294b9f76f289e8d97ecd737
32. 32
  Hulme, E. C.; Trevethick, M. A. Ligand Binding Assays at Equilibrium: Validation and Interpretation Br. J. Pharmacol. 2010, 161, 1219– 1237 DOI: 10.1111/j.1476-5381.2009.00604.x
  32
  Ligand binding assays at equilibrium: validation and interpretation
  Hulme, Edward C.; Trevethick, Mike A.
  British Journal of Pharmacology (2010), 161 (6), 1219-1237CODEN: BJPCBM; ISSN:1476-5381. (Wiley-Blackwell)
  The focus of this review paper is factors affecting data interpretation in ligand binding assays under equil. conditions. Protocols for detg. Kd (the equil. dissocn. const.) and KdA (the equil. inhibitor const.) for receptor ligands are discussed. The basic theory describing the interaction of a radiotracer and an unlabeled competitor ligand with a receptor is developed. Inappropriate exptl. design may result in ligand depletion and non-attainment of equil., distorting the calcn. of Kd and KdA. Strategies, both theor. and practical, will be given to avoid and correct such errors, thus leading to the detn. of reliable values for these consts. In detg. KdA from competition binding studies, two addnl. concepts are discussed. First, the necessity to measure an adequate specific binding signal from the bound radiotracer ligand limits the range of affinity consts. that can be measured: a particular set of assay conditions may lead to an upper limit on the apparent affinity of unlabeled ligands. Second, an extension of the basic assay methodol. can indicate whether the interaction between the tracer and a test ligand is mediated by a competitive or an allosteric mechanism. Finally, the review ends with a discussion of two factors that are often overlooked: buffer compn. and the temp. at which the assay is conducted, and the impact these can have on affinity measurements and the understanding of drug interactions.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhsFWhsr3J&md5=03875d96fbc7ae409b8f4c8a084dbc99
33. 33
  Broder, G. R.; Ranasinghe, R. T.; Neylon, C.; Morgan, H.; Roach, P. L. Kinetics and Thermodynamics of Biotinylated Oligonucleotide Probe Binding to Particle-Immobilized Avidin and Implications for Multiplexing Applications Anal. Chem. 2011, 83, 2005– 2011 DOI: 10.1021/ac102762q
  33
  Kinetics and Thermodynamics of Biotinylated Oligonucleotide Probe Binding to Particle-Immobilized Avidin and Implications for Multiplexing Applications
  Broder, Graham R.; Ranasinghe, Rohan T.; Neylon, Cameron; Morgan, Hywel; Roach, Peter L.
  Analytical Chemistry (Washington, DC, United States) (2011), 83 (6), 2005-2011CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)
  In this work, the kinetics and dissocn. const. for the binding of a biotin-modified oligonucleotide to microparticle-immobilized avidin were measured. Avidin has been immobilized by both covalent coupling and bioaffinity capture to a surface prefunctionalized with biotin. The measured rate and equil. dissocn. consts. of avidin immobilized by these different methods have been compared with those for nonimmobilized avidin. The authors found that immobilization resulted in both a decrease in the rate of binding and an increase in the rate of dissocn. leading to immobilized complexes having equil. dissocn. consts. of 7±3 × 10-12 M, higher than the value measured for the complex between biotin-modified oligonucleotide and nonimmobilized avidin and approx. 4 orders of magnitude larger than values for the wild-type avidin-biotin complex. Immobilized complex half-lives were reduced to 5 days, which resulted in biotin ligands migrating between protein attached to different particles. Different immobilization methods showed little variation in complex stability but differed in total binding and nonspecific biotin-modified oligonucleotide binding. These findings are crit. for the design of multiplexed assays where probe mols. are immobilized to biosensors via the avidin-biotin interaction.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhsVektLs%253D&md5=beef8a51efd3dea3fcbe330c152c3e77
34. 34
  Noor, M. O.; Krull, U. J. Camera-Based Ratiometric Fluorescence Transduction of Nucleic Acid Hybridization with Reagentless Signal Amplification on a Paper-Based Platform Using Immobilized Quantum Dots as Donors Anal. Chem. 2014, 86, 10331– 10339 DOI: 10.1021/ac502677n
  34
  Camera-Based Ratiometric Fluorescence Transduction of Nucleic Acid Hybridization with Reagentless Signal Amplification on a Paper-Based Platform Using Immobilized Quantum Dots as Donors
  Noor, M. Omair; Krull, Ulrich J.
  Analytical Chemistry (Washington, DC, United States) (2014), 86 (20), 10331-10339CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)
  Paper-based diagnostic assays are gaining increasing popularity for their potential application in resource-limited settings and for point-of-care screening. Achievement of high sensitivity with precision and accuracy can be challenging when using paper substrates. Herein, the authors implement the red-green-blue color palette of a digital camera for quant. ratiometric transduction of nucleic acid hybridization on a paper-based platform using immobilized quantum dots (QDs) as donors in fluorescence resonance energy transfer (FRET). A nonenzymic and reagentless means of signal enhancement for QD-FRET assays on paper substrates is based on the use of dry paper substrates for data acquisition. This approach offered at least a 10-fold higher assay sensitivity and at least a 10-fold lower limit of detection (LOD) as compared to hydrated paper substrates. The surface of paper was modified with imidazole groups to assemble a transduction interface that consisted of immobilized QD-probe oligonucleotide conjugates. Green-emitting QDs (gQDs) served as donors with Cy3 as an acceptor. A hybridization event that brought the Cy3 acceptor dye in close proximity to the surface of immobilized gQDs was responsible for a FRET-sensitized emission from the acceptor dye, which served as an anal. signal. A hand-held UV lamp was used as an excitation source and ratiometric anal. using an iPad camera was possible by a relative intensity anal. of the red (Cy3 photoluminescence (PL)) and green (gQD PL) color channels of the digital camera. For digital imaging using an iPad camera, the LOD of the assay in a sandwich format was 450 fmol with a dynamic range spanning 2 orders of magnitude, while an epifluorescence microscope detection platform offered a LOD of 30 fmol and a dynamic range spanning 3 orders of magnitude. The selectivity of the hybridization assay was demonstrated by detection of a single nucleotide polymorphism at a contrast ratio of 60:1. This work provides an important framework for the integration of QD-FRET methods with digital imaging for a ratiometric transduction of nucleic acid hybridization on a paper-based platform.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsFKns77P&md5=e37bec4a9c00170d444fc47adf9cfaaa
35. 35
  Yang, Y.; Li, C.; Yin, L.; Liu, M.; Wang, Z.; Shu, Y.; Li, G. Enhanced Charge Transfer by Gold Nanoparticle at DNA Modi Fi Ed Electrode and Its Application to Label-Free DNA Detection ACS Appl. Mater. Interfaces 2014, 6, 7579– 7584 DOI: 10.1021/am500912m
  There is no corresponding record for this reference.
36. 36
  Kang, T.; Yoo, S. M.; Yoon, I.; Lee, S. Y.; Kim, B. Patterned Multiplex Pathogen DNA Detection by Au Particle-on-Wire SERS Sensor Nano Lett. 2010, 10, 1189– 1193 DOI: 10.1021/nl1000086
  36
  Patterned multiplex pathogen DNA detection by Au particle-on-wire SERS sensor
  Kang, Taejoon; Yoo, Seung Min; Yoon, Ilsun; Lee, Sang Yup; Kim, Bongsoo
  Nano Letters (2010), 10 (4), 1189-1193CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)
  A gold particle-on-wire system that can be used as a specific, sensitive, and multiplex DNA sensor is developed. A pattern formed by multiple Au nanowire sensors provides positional address and identification for each sensor. By using this system, multiplex sensing of target DNAs was possible in a quant. manner with a detection limit of 10 pM. Target DNAs from ref. bacteria and clin. isolates were successfully identified by this sensor system, enabling diagnostics for infectious diseases.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXjtFSjs7g%253D&md5=79134bae75d137af1c56341a3d3b7168
37. 37
  López, M. S.; Cabanillas, G. F.; Castañón, M. J. L.; López-Ruiz, B. Development of a Genosensor for Peanut Allergen ARA H 2 Detection and Its Optimization by Surface Response Methodology Biosens. Bioelectron. 2014, 62, 350– 356 DOI: 10.1016/j.bios.2014.06.065
  There is no corresponding record for this reference.
38. 38
  Du, Y.; Guo, S.; Dong, S.; Wang, E. An Integrated Sensing System for Detection of DNA Using New Parallel-Motif DNA Triplex System and Graphene-Mesoporous Silica-Gold Nanoparticle Hybrids Biomaterials 2011, 32, 8584– 8592 DOI: 10.1016/j.biomaterials.2011.07.091
  38
  An integrated sensing system for detection of DNA using new parallel-motif DNA triplex system and graphene-mesoporous silica-gold nanoparticle hybrids
  Du, Yan; Guo, Shaojun; Dong, Shaojun; Wang, Erkang
  Biomaterials (2011), 32 (33), 8584-8592CODEN: BIMADU; ISSN:0142-9612. (Elsevier Ltd.)
  In this article, we demonstrate the use of graphene-mesoporous silica-gold NP hybrids (GSGHs) as an enhanced element of the integrated sensing platform for the ultra-sensitive and selective detection of DNA by using strand-displacement DNA polymn. and parallel-motif DNA triplex system as dual amplifications. We find that the present new sensing strategy based on GSGHs is able to detect target DNA with a fairly high detection sensitivity of 10 fm through the hybridization of duplex DNA to the acceptor DNA for the formation of parallel-motif DNA triplex on the multilayer film (contg. GSGHs and redox probe) modified functional interface, and even has a good capability to investigate the single nucleotide polymorphisms (SNPs). The detection limit for target DNA is about two orders of magnitude lower than that of graphene-based DNA electrochem. impedance spectroscopy (EIS) sensor (6.6 pm), four orders of magnitude lower than those of graphene-based DNA sensors coupled with fluorescent assay (100 pm and 1 nm) and five orders of magnitude lower than those of field effect transistor (FET)-based assays (1 nm and 2 nm). Most importantly, our present sensing system can also be facilely achieved in the ITO electrode array, which is of paramount importance for possible multiplex anal. in lab-on-chip.
  >> More from SciFinder ^®
  https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhtFOlsrrE&md5=bf41573654fe52b413f8287c89889293
Supporting Information
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsami.7b00575.
- Materials, synthesis, characterization and detection method (PDF)
- am7b00575_si_001.pdf (758.97 kb)
Terms & Conditions

Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

Oligonucleotide Sensor Based on Selective Capture of Upconversion Nanoparticles Triggered by Target-Induced DNA Interstrand Ligand ReactionClick to copy article linkArticle link copied!

ACS Applied Materials & Interfaces

Abstract

1 Introduction

2 Materials

3 Characterization

4 Experimental Section

Scheme 1

5 Results and Discussion

5.1 Particle Preparation, Characterization, and Functionalization

Figure 1

5.2 Well-Plate Signal Detection and Protocol Optimization

5.2.1 Interstrand Ligand Reaction

Scheme 2

Figure 2

5.2.2 Binding Kinetic Experiments

Figure 3

5.2.3 Sensor Calibration

Figure 4

Figure 5

Scheme 3

6 Conclusions

Supporting Information

Terms & Conditions

Author Information

Acknowledgment

References

Cited By

ACS Applied Materials & Interfaces

Article Views

Altmetric

Citations

Recommended Articles

Abstract

Scheme 1

Figure 1

Scheme 2

Figure 2

Figure 3

Figure 4

Figure 5

Scheme 3

References

Supporting Information

Supporting Information

Terms & Conditions

Oligonucleotide Sensor Based on Selective Capture of Upconversion Nanoparticles Triggered by Target-Induced DNA Interstrand Ligand Reaction
Click to copy article linkArticle link copied!