CN116377030A - Colorimetric method miRNA sensor based on graphene oxide coated gold nanoparticles, material and application of colorimetric method miRNA sensor - Google Patents
Colorimetric method miRNA sensor based on graphene oxide coated gold nanoparticles, material and application of colorimetric method miRNA sensor Download PDFInfo
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Abstract
The invention discloses a colorimetric method miRNA sensor based on graphene oxide coated gold nanoparticles, a material and application thereof. Based on electrostatic interaction, the GO-AuNPs composite particles are prepared, and the graphene oxide can amplify the LSPR effect of the composite particles, so that the sensitivity and stability of the sensor are improved. When the RNA probe fixed on the surface of the graphene oxide-gold nanocomposite particle and target RNA undergo sandwich hybridization reaction, the distance between GO-AuNPs particles is reduced, the local surface plasma effect of the particles is influenced, the local surface plasma peak position changes, and the color of the solution is changed from red to purple. The qualitative detection of the target miRNA can be realized by observing the color change by naked eyes; based on the LSPR effect of the composite material, quantitative detection of miRNA is realized by combining an ultraviolet-visible spectrophotometer. The method overcomes the defects of time consumption, high cost and the like of the traditional method, realizes the rapid, sensitive and stable detection of the target miRNA, and provides a novel method and path for the detection and application of the miRNA sensor.
Description
Technical Field
The invention relates to the field of miRNA detection, in particular to a colorimetric miRNA sensor based on graphene oxide coated gold nanoparticles, a material and application thereof.
Background
Lung cancer is one of the most rapidly growing malignancies with current morbidity and mortality, and severely threatens the physical health of humans. If it can be found and treated in early stage of lung cancer, it can greatly raise the survival rate of lung cancer treatment, so that it is necessary for early diagnosis and prognosis of lung cancer. miRNAs are widely involved in evolutionary processes such as tumor development, invasion and metastasis, drug resistance, etc., and are considered as biomarkers for early tumor discovery, classification and predictive diagnosis. However, the short sequence and high similarity characteristics of mirnas greatly limit the development of their detection means. Therefore, research and development of a rapid, sensitive, label-free, high-stability, low-cost miRNA detection technology has become an important topic in the clinical medicine field.
Heretofore, the means for detecting miRNAs have mainly involved northern blot analysis with radiolabeled probes, gene chip technology, polymerase Chain Reaction (PCR) based and the like. Among them, northern blotting is a common method for analyzing miRNAs based on hybridization, but in this process, radioactive elements are required to be used as labeling probes, which have a certain risk and are difficult to design, and cannot meet the standards of clinical practical technologies; the gene chip technology is a high-throughput multi-component simultaneous analysis method, but the method needs a large instrument and has poor repeatability; the quantitative PCR method has the defects of low sensitivity, complicated operation, easy generation of false positive signals and the like. Therefore, developing a rapid, sensitive, label-free, highly stable, inexpensive technique for detecting miRNAs is an important topic in the academic and clinical fields.
Disclosure of Invention
The invention provides a colorimetric method miRNA sensor based on graphene oxide coated gold nanoparticles (GO-Au) for solving the problems that an existing miRNA detection means is complex, an instrument is expensive, detection time is long and the like. The gold nanoparticles are fixed on the surface of the graphene oxide or are coated in the graphene oxide by a chemical bond method, so that aggregation of the gold nanoparticles is reduced, and possibility is provided for improving the sensitivity of the sensor and reducing the detection lower limit of the sensor. And respectively fixing RNA1 and RNA2 which are complementarily paired with the specific base of the target miRNA on the GO-Au surface to prepare the sensing probe for specific response of the target miRNA. The detection of the target miRNA is realized by utilizing sandwich hybridization reaction, the color of the solution changes from red to purple, and the detection of the miRNA can be realized by observing the color change by naked eyes or an ultraviolet-visible spectrophotometer. Provides a method and means with high sensitivity and low detection limit for miRNAs detection, and has important scientific significance and great practical value for promoting the development and application of miRNA detection technology.
The technical scheme adopted by the invention is as follows:
the colorimetric method miRNA sensor based on the graphene oxide coated gold nano particles is characterized in that the sensor uses graphene oxide coated gold nano composite particles as a carrier, and an RNA probe is functionalized on the surfaces of the composite particles, so that miRNA detection is realized based on sandwich hybridization reaction.
Preferably, when the RNA probe fixed on the surface of the composite particle and target RNA undergo sandwich hybridization reaction, the distance between GO-AuNPs particles is reduced, the LSPR effect of the particles is influenced, the LSPR peak position of the particles changes, the color of the solution changes from red to purple, and the qualitative detection of the target miRNA is realized by observing the color change by naked eyes; based on the LSPR effect of the composite material, quantitative detection of miRNA is realized by combining an ultraviolet-visible spectrophotometer.
Preferably, the RNA probes are GO-AuNPs-RNAprobe1 and GO-AuNPs-RNAprobe2, which respectively only accord with the base complementary pairing principle with the target miRNA, and do not accord with the base complementary pairing principle with each other.
Further preferably, taking miRNA-126 as an example, the segment of miRNA-126 is the nucleotide sequence shown in SEQ ID NO. 1, and the corresponding RNA probe can be designed into the nucleotide sequence shown in SEQ ID NO. 2 and the nucleotide sequence shown in SEQ ID NO. 3.
Preferably, in the sensitive material, gold nanoparticles coated with graphene oxide are combined based on electrostatic action, and the gold nanoparticles are coated inside the graphene oxide; RNAprobe can be immobilized on the surface of the composite particle by chemical cross-linking using sulfhydryl groups.
Preferably, graphene oxide can amplify the LSPR effect of the composite particles, increasing the sensitivity and stability of the sensor.
Preferably, the gold nanoparticles are prepared by adopting a water phase reduction method, graphene Oxide (GO) is synthesized by adopting a Hummers method, and the GO-AuNPs composite particles specifically comprise the following steps:
(1) Cleaning glassware required in experiments by using aqua regia, washing with deionized water, and drying for later use;
the cleaning of the reaction environment can avoid introducing impurities in the growth process of AuNPs;
(2) Adding a trisodium citrate solution into the boiled chloroauric acid solution, and continuing the reaction when the color of the mixed solution is observed to be changed from light yellow to black and finally to be changed into wine red so as to obtain AuNPs with different particle sizes;
(3) The preparation method of the GO-AuNPs composite material comprises the following steps: and mixing the synthesized AuNPs solution and the GO solution according to different proportions, and stirring to obtain the GO-AuNPs composite particles, wherein oxygen-containing groups on the surface of GO can promote the embedding of GO into AuNPs, so that the GO-AuNPs composite particles are formed.
A colorimetric method miRNA sensor sensing Probe based on graphene oxide coated gold nanoparticles comprises the following preparation steps of the GO-AuNPs-RNA Probe composite material:
step one preparation of GO-AuNPs-RNAp: dispersing the prepared GO-AuNPs solution in PBS buffer solution after washing for a plurality of times, respectively adding TCEP aqueous solution into RNA probe1 and RNA probe2 to activate sulfhydryl at the end of the solution, adding the activated RNA probe into the GO-AuNPs solution, and incubating at room temperature;
step two, salinization of GO-AuNPs-RNAp: adding NaCl into the GO-AuNPs-RNA probe1 and GO-AuNPs-RNA probe2 solutions respectively, incubating after ultrasonic treatment, repeatedly adding NaCl for multiple times, and continuing incubating;
step three, sample washing: the incubation solution was centrifuged with PBS, and unbound RNA was removed from the solution and dispersed in buffer PBS.
The colorimetric method miRNA sensor based on graphene oxide coated gold nanoparticles senses or the probe is used for quantitative detection of RNA, and the UV-Vis absorption spectrum of GO-AuNPs-RNAp1, GO-AuNPs-RNAp2 and a target detector miRNA-126 solution are detected after mixed incubation.
The invention has the beneficial effects that:
(1) Realizes the stable detection of miRNA-126, has good biocompatibility and has good application prospect in the early diagnosis field of lung cancer.
(2) The colorimetric sensor for detecting miRNA-126 provided by the invention has the advantages of economy, rapidness, sensitivity, stable performance, simple structure, easiness in preparation and the like, and shows good selectivity. Provides a new approach and strategy for developing a stable and economical detection probe for early diagnosis markers of cancers.
Drawings
FIG. 1 GO-AuNPs composite particle, (a) UV absorption spectrum and TEM images (b), (c);
FIG. 2 UV-visible spectra of AuNPs, GO-AuNPs-RNAp1 and GO-AuNPs-RNAp 2;
FIG. 3 is an infrared spectrum of GO, GO-AuNPs and GO-AuNPs-RNAp complexes;
FIG. 4 is a schematic diagram of a miRNA-126 colorimetric sensor based on GO-AuNPs-RNAp complexes;
FIG. 5 (a) UV-visible spectra of complexes containing different concentrations of miRNA-126; (b) relationship of Δλ to miRNA-126 concentration;
the selectivity of the sensor of fig. 6;
FIG. 7 survival of cells after incubation with GO-AuNPs composite particles at different concentrations for different times.
Detailed Description
The invention will be further illustrated with reference to specific examples. The present invention will be described in further detail with reference to examples, but is not limited to these examples.
Example 1
A colorimetric method miRNA-126 detection method of graphene oxide coated gold nanoparticles comprises the following steps:
step 1: gold nanoparticles were prepared by aqueous phase reduction, and Graphene Oxide (GO) was synthesized by Hummers method. And cleaning glassware required in the experiment by using aqua regia, washing with deionized water, and drying for later use. The reaction environment is cleaned to avoid introducing impurities during the growth of AuNPs. To a boiling chloroauric acid solution (0.01% (w/w), 50 mL) was added 0.75mL of trisodium citrate solution (1% (w/w), and when the color of the mixture was observed to change from pale yellow to black and finally to reddish wine, the reaction was continued for 30min to obtain AuNPs of different particle sizes.
Step 2: and preparing the graphene oxide coated gold nanocomposite by utilizing the electrostatic bonding effect. And mixing the synthesized AuNPs solution and the GO solution according to the proportion of 2:1, and stirring for 2 hours and then preserving for later use. The oxygen-containing groups on the surface of the GO promote the embedding of the GO into the AuNPs, so that the GO-AuNPs composite particles are formed.
As shown in FIG. 1, the absorption spectra of AuNPs and GO-AuNPs composite particles were measured by an ultraviolet spectrophotometer, and as shown in FIG. 1 (a), the introduction of GO did not destroy the ultraviolet absorption characteristics of AuNPs, and the composite particles had a characteristic absorption peak at 525nm, which was caused by the LSPR effect of GO-AuNPs composite particles. The composite particles had smaller half-peak widths of absorption peaks than gold nanoparticles alone, indicating that the introduction of GO increased the stability of its LSPR phenomenon. The morphology and the size of the composite particles are characterized by using TEM, and the results are shown in fig. 1 (b) and (c), the black dots are gold nanoparticles, GO is coated around the black dots, the particle size of the GO-AuNPs composite particles is uniform, and the diameter of the GO-AuNPs composite particles is about 37nm. Indicating that the required GO-AuNPs composite particles have been synthesized.
Step 3: and modifying auxiliary RNA probes (GO-AuNPs-RNAprobe 1 and GO-AuNPs-RNAprobe 2) on the surface of the GO-AuNPs by a chemical crosslinking method. The resulting GO-AuNPs solution was washed multiple times and then dispersed in PBS (10 mm,0.01% (w/w) SDS, ph=6.8) buffer. TCEP (10. Mu.M) in water was added to RNAp1 and RNAp2, respectively, to activate the thiol groups at the ends, and the activated RNA probe was added to GO-AuNPs solution and incubated at room temperature for 12h. Adding a small amount of 2M NaCl into the GO-AuNPs-RNAp1 and GO-AuNPs-RNAp2 solutions respectively, performing ultrasonic treatment for 10s, incubating for 1h, repeatedly adding NaCl until the NaCl concentration is 0.1M, and further incubating for 24h. The incubation was washed by centrifugation with PBS, unbound RNA was removed from the solution and dispersed in buffer PBS (10 mm,0.01% (w/w) SDS,0.3M NaCl,pH =6.8).
The end-modified RNAp is used for chemical crosslinking with the GO-AuNPs composite particles, UV-Vis absorption spectra of AuNPs, GO-AuNPs and GO-AuNPs-RNAp composite are shown in figure 2, after RNAp modification, LSPR absorption peaks of the GO-AuNPs composite particles are subjected to a small red shift, which shows that RNAp is successfully crosslinked to the surfaces of the GO-AuNPs composite particles to form GO-AuNPs-RNAp composite.
As shown in fig. 3, to further confirm whether RNAp was successfully modified on the surface of GO-AuNPs, fourier transform infrared spectrometer was used to determine the variation of characteristic peaks before and after modification of GO-AuNPs with RNAp. As can be seen from the infrared spectrogram, the unmodified AuNPs have the following characteristic peaks respectively located at 3427cm -1 (-OH stretching vibration), 2925cm -1 、2855cm -1 (-CH 2 Antisymmetric telescopic vibration, symmetrical telescopic vibration) 1727cm -1 (C=O stretching vibration), 1200cm -1 Nearby (C-O stretching vibration), these are characteristic peaks of sodium citrate adsorbed on the gold nanoparticle surface as a protective agent, not all of the gold particles themselves. GO-AuNPs retain the characteristic peaks of AuNPs and are 1411cm in length -1 And 1060cm -1 Where are represented by C-O and C-O-C groups in GO, respectivelyStrong peaks caused by stretching vibration. After RNA modification, the infrared spectrogram of the GO-AuNPs-RNAp compound shows that besides all characteristic peaks of the sodium citrate on the surface, the characteristic peak 875cm of the nucleotide structure is also present -1 、991cm -1 (ring vibration of base five-carbon sugar and C-O vibration on ring), 632cm -1 (C-S stretching vibration) the characteristic peaks to which these novel nucleotides belong indicate that RNAp binds successfully to the surface of GO-AuNPs via covalent bonds.
Step 4: and (3) carrying out miRNA visual detection based on a base complementary pairing principle. The GO-AuNPs have a strong local surface plasma absorption effect, and show obvious extinction peaks under an ultraviolet-visible spectrophotometer, and after being combined with the RNA probe1 and the RNA probe2, the formed GO-AuNPs-RNAp1 and GO-AuNPs-RNAp2 still keep the extinction peaks unchanged. As shown in FIG. 4, when two complexes (GO-AuNPs-RNAp 1 and GO-AuNPs-RNAp 2) are mixed together, hybridization reaction does not occur in the system due to non-complementarity of the base sequences of RNA, and GO-AuNPs-RNAp1 and GO-AuNPs-RNAp2 still have good dispersibility. However, after the miRNA-126 solution is added into the mixed solution system, the hybridization reaction of the sandwich of the system starts to happen, which leads the GO-AuNPs-RNAp1 and GO-AuNPs-RNAp2 to gradually change from a dispersion state to an aggregation state, the surface plasmon resonance between the gold nanoparticles is coupled, GO further expands the coupling degree, the initial LSPR peak of the GO-AuNPs is red shifted, and the color of the solution changes from red to purple. Thus, we can detect different concentrations of the target miRNA-126 by a change in the UV-Vis absorbance spectrum.
And mixing and incubating the GO-AuNPs-RNAp1 and GO-AuNPs-RNAp2 with the miRNA-126 solution of the target detector, and detecting the UV-Vis absorption spectrum of the target detector. And mixing and incubating the GO-AuNPs-RNAp1 and GO-AuNPs-RNAp2 with the miRNA-126 solution of the target detector, and detecting the UV-Vis absorption spectrum of the target detector. The specific method comprises the following steps: 50. Mu.L of miRNA-126 solution was added to 450. Mu.L of buffer containing two GO-AuNPs-RNAp complexes (225. Mu.L each), and the mixture was heated in a water bath at 60℃for 5min, naturally cooled to room temperature and incubated for a period of time. The absorbance spectrum of the mixture was tested, and the concentration of miRNA-126 was calculated from the change in absorbance spectrum.
As shown in fig. 5, in order to study the detection performance of the colorimetric sensor, the detection lower limit and the test range of the sensor must be studied. FIG. 5 (a) shows UV-Vis absorbance spectra of GO-AuNPs-RNAp tested at different miRNA-126 concentrations. Quantitative detection of miRNA-126 was performed at a concentration ranging from 0.1nM to 0.1. Mu.M, with the detection concentration increasing by 10-fold. The trend of the variation of the peak position of the absorption peak under different miRNA-126 concentration conditions is shown in figure 5, wherein Deltalambda is defined as the drift amount of the ultraviolet absorption peak of the compound when the miRNA concentration is increased. The smaller the value of Δλ indicates a lower degree of complex agglomeration. Delta lambda showed an exponential change in the concentration range of 0.1nM to 100nM, and the standard curve equation was: Δλ=1.7 log 10 C+2.9(R 2 =0.98), the lower detection limit can reach 0.1nM. Compared with other recently reported detection methods, the detection method has lower detection lower limit and has important significance for clinical application.
Example 2
In order to make the sensing system possible in the practical application of clinical diagnosis, the method has important significance in carrying out the selective experiment on the target miRNA-126. We prepared several 1nM solutions of other miRNAs (miRNA-148 a, miRNA-21, miRNA-106 and random sequences) to study the specificity of the colorimetric sensor for miRNA-126 detection. The miRNAs sample solution with the concentration of 1nM is respectively added into the GO-AuNPs-RNAp complex solution, and the solution without any RNA is used as a blank control group for experimental detection. As shown in FIG. 6, it was found that the RNA probe was not base-paired with the miRNA sample at the same concentration, and thus the hybridization reaction was hardly triggered, and the absorbance was slightly changed. In contrast, only the miRNA-126 solution base-paired with the RNA probe was able to smoothly perform hybridization reaction, causing aggregation of GO-AuNPs, and the change in absorbance of the sample solution was clearly observed. By comparing the absorbance of each group of sample solutions, the colorimetric sensor is confirmed to have good selectivity.
Example 3
Low cytotoxicity and biocompatibility are one of the important properties of sensitive materials in biosensors. To investigate the biocompatibility of GO-AuNPs composite particles in vivo, we performed cytotoxicity assays using the CCK-8 method.
The GO-AuNPs composite particle cytotoxicity assay was performed using SY5Y cells by means of a cell counting kit (Cell Counting Kit, CCK-8). The flow is as follows: (1) Cells in the growth phase are digested with trypsin, which breaks down various extracellular proteins contained outside the cells and prevents the cells from sticking together, thereby obtaining individual cells, which are arranged as a cell suspension, dispersed in a 96-well plate. (2) The well plate containing the cells was placed in an incubator for culturing, and the cells were allowed to grow on the wall for 24 hours. (3) And replacing a cell culture medium, wherein a control group is a culture medium without the GO-AuNPs solution, an experimental group is a culture medium with the GO-AuNPs solution subjected to extraction and purification, and respectively culturing cells of the experimental group and the control group corresponding to each experimental group for 48 hours and 24 hours, wherein each sample concentration is repeated for more than three times. (4) The absorbance of the system was recorded with the aid of a microplate reader, and the cell viability was calculated from the absorbance of the cells (formula 1) three times.
Wherein D is s For the absorbance of the experimental group, D b Absorbance of the blank group, D c Absorbance was used as control.
Cells were cultured in pure AuNPs, GO and different ratios of GO-AuNPs composite particles for 24h and 48h, respectively. Fig. 7 shows the survival rate of cells after being cultured for different time by the composite particles of the GO-AuNPs with different concentrations, and as can be seen from fig. 7, the composite particles of the composite particles have obvious low toxicity to the cells, and the survival rate of the cells of all materials is more than 85%. This demonstrates that the GO-AuNPs composite particles have very low biotoxicity and good biocompatibility, and can be applied to biosensor preparation, cell imaging and cell testing.
Example 4
A colorimetric method miRNA-21 detection method of graphene oxide coated gold nanoparticles selects RNA probes 1 and 2 combined with miRNA-21 specific response, and the rest methods are the same as in example 1, so as to construct a sensor for the miRNA-21 specific response.
Example 5
The ratio of GO to AuNPs was adjusted to 1:1, preparing GO-AuNPs composite particles, and the other steps are the same as in the embodiment 1, wherein the composite particles can also realize the specific detection of target miRNA.
Claims (9)
1. The colorimetric method miRNA sensor based on the graphene oxide coated gold nano particles is characterized in that the sensor uses graphene oxide coated gold nano composite particles as a carrier, and an RNA probe is functionalized on the surfaces of the composite particles, so that miRNA detection is realized based on sandwich hybridization reaction.
2. The colorimetric miRNA sensor based on graphene oxide coated gold nanoparticles according to claim 1, wherein when the RNA probe immobilized on the surface of the composite particle undergoes a sandwich hybridization reaction with the target RNA, the distance between GO-AuNPs particles is reduced, the LSPR effect of the particles is affected, the LSPR peak position of the particles is changed, the color of the solution is changed from red to purple, and qualitative detection of the target miRNA is achieved by observing the color change by naked eyes; based on the LSPR effect of the composite material, the quantitative detection of MiRNA is realized by combining an ultraviolet-visible spectrophotometer.
3. The colorimetric miRNA sensor based on graphene oxide coated gold nanoparticles according to claim 1, wherein the RNA probes are GO-AuNPs-RNA probe1 and GO-AuNPs-RNA probe2, which respectively conform to the base complementary pairing principle only with the target mirnas and do not conform to the base complementary pairing principle.
4. The colorimetric miRNA sensor based on the graphene oxide coated gold nanoparticles according to claim 3, wherein, taking miRNA-126 as an example, the segment of miRNA-126 is the nucleotide sequence shown in SEQ ID NO. 1, and the corresponding RNA probes can be designed into the nucleotide sequence shown in SEQ ID NO. 2 and the nucleotide sequence shown in SEQ ID NO. 3.
5. The colorimetric miRNA sensor based on graphene oxide coated gold nanoparticles according to claim 1, wherein in the sensitive material, the graphene oxide coated gold nanoparticles are combined based on electrostatic action, and the gold nanoparticles are coated inside the graphene oxide; RNA probe can be immobilized on the surface of the composite particle by using sulfhydryl groups through a chemical crosslinking method.
6. A colorimetric miRNA sensor based on graphene oxide-coated gold nanoparticles according to claim 1, wherein graphene oxide amplifies LSPR effect of the composite particles and increases sensitivity and stability of the sensor.
7. The colorimetric miRNA sensor based on graphene oxide coated gold nanoparticles according to claim 1, wherein the gold nanoparticles are prepared by an aqueous phase reduction method, graphene Oxide (GO) is synthesized by a Hummers method, and the GO-AuNPs composite particles specifically comprise the following steps:
(1) Cleaning glassware required in experiments by using aqua regia, washing with deionized water, and drying for later use; the cleaning of the reaction environment can avoid introducing impurities in the growth process of AuNPs;
(2) Adding a trisodium citrate solution into the boiled chloroauric acid solution, and continuing the reaction when the color of the mixed solution is observed to be changed from light yellow to black and finally to be changed into wine red so as to obtain AuNPs with different particle sizes;
(3) The preparation method of the GO-AuNPs composite material comprises the following steps: and mixing the synthesized AuNPs solution and the GO solution according to different proportions, and stirring to obtain the GO-AuNPs composite particles, wherein oxygen-containing groups on the surface of GO can promote the embedding of GO into AuNPs, so that the GO-AuNPs composite particles are formed.
8. The colorimetric method miRNA sensor sensing Probe based on the graphene oxide coated gold nanoparticles is characterized by comprising the following preparation steps of the GO-AuNPs-RNA Probe composite material:
step one preparation of GO-AuNPs-RNAp: dispersing the prepared GO-AuNPs solution in PBS buffer solution after washing for a plurality of times, respectively adding TCEP aqueous solution into RNA probe1 and RNA probe2 to activate sulfhydryl at the end of the solution, adding the activated RNA probe into the GO-AuNPs solution, and incubating at room temperature;
step two, salinization of GO-AuNPs-RNAp: adding NaCl into the GO-AuNPs-RNA probe1 and GO-AuNPs-RNA probe2 solutions respectively, incubating after ultrasonic treatment, repeatedly adding NaCl for multiple times, and continuing incubating;
step three, sample washing: the incubation solution was centrifuged with PBS, and unbound RNA was removed from the solution and dispersed in buffer PBS.
9. The colorimetric miRNA sensor sensing based on graphene oxide-coated gold nanoparticles according to any one of claims 1 to 4 or the probe according to claim 7 for quantitative detection of RNA, characterized by the following detection steps: and mixing and incubating the GO-AuNPs-RNAp1 and GO-AuNPs-RNAp2 with the miRNA-126 solution of the target detector, and detecting the UV-Vis absorption spectrum of the target detector.
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| CN115308144B (en) * | 2022-07-21 | 2024-07-05 | 三峡大学 | Optical fiber miRNA sensor based on graphene oxide coated gold nanoparticles, material, probe and application of optical fiber miRNA sensor |
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| CN115308144A (en) * | 2022-07-21 | 2022-11-08 | 三峡大学 | Optical fiber miRNA sensor, material and probe based on graphene oxide coated gold nanoparticles and application of optical fiber miRNA sensor |
| CN115308144B (en) * | 2022-07-21 | 2024-07-05 | 三峡大学 | Optical fiber miRNA sensor based on graphene oxide coated gold nanoparticles, material, probe and application of optical fiber miRNA sensor |
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