A Raman sensor for rapid detection of new coronavirus based on optofluidic microstructured optical fiber and SERS substrate
By chemically bonding the growth of nanosilver/nanographene oxide/nanogold particles in optical flow-controlled microstructured fibers and combining with ACE2 receptors, rapid and sensitive detection of the new coronavirus is achieved, and the costly and cumbersome detection in the existing technology is solved. , the time-consuming problem has the advantages of high efficiency, low cost and simple operation.
Patent Information
- Application Number
- CN202211073119.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2022-09-02
- Publication Date
- 2024-12-10
- Estimated Expiration
- 2042-09-02
AI Technical Summary
The existing methods of COVID-19 detection are expensive, cumbersome, and time-consuming. The conventional methods are susceptible to factors such as specimen quality, virus infection location and expression, and cannot be diagnosed quickly and accurately.
Raman sensor for rapid detection of new coronavirus virus is adopted based on optical flow-controlled microstructured fibers and SERS substrates. Nanosilver/nanographene oxide/nanogold particles are grown by chemical bonding on the surface of the suspension core inside the hollow fiber, and combined with ACE2 receptors for function. to achieve specific binding of SARS-CoV-2, and to achieve flow injection function through microsyringe pump.
It realizes rapid detection with high sensitivity, fast response speed, small sample consumption and strong anti-interference ability, reduces detection costs, simplifies operating procedures, and improves detection efficiency and accuracy.
Smart Images
Figure CN115508331B_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to a Raman sensor for rapid detection of the novel coronavirus based on an integrated optofluidic microstructure optical fiber and a SERS substrate, in particular to a Raman sensor for rapid detection based on a natural microfluidic optical fiber, with nanosilver / nanographene oxide / nanogold particles functionalized with ACE2 as a special SERS substrate integrated, which can specifically bind to SARS-CoV-2 and has a flow sampling function. Background Art
[0002] Since 2019, coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly around the world. At present, conventional epidemic prevention and control measures are the most effective measures to prevent the large-scale spread of the epidemic. More and more researchers are working in this field. The current methods for detecting viruses include reverse transcription polymerase chain reaction (RT-PCR), fluorescence detection, and immunological detection. However, the above methods require a long detection time and require samples to be labeled in advance. The operation is cumbersome and time-consuming, and the test results are easily affected by many factors such as specimen quality, virus infection site and expression level. In contrast, the surface enhanced Raman scattering (SERS) detection method has the advantages of label-free, rapid, and high sensitivity, and has good application prospects in rapid and accurate diagnosis and prevention of disease transmission.
[0003] In the process of testing the new coronavirus, in order to avoid sample leakage during the test and prevent the virus from spreading over a large area, a very small amount of test samples should be taken during the test. Fiber optic sensors have attracted widespread attention due to their high sensitivity, resistance to electromagnetic interference, and small size. In particular, some optical fibers with special structures, such as hollow optical fibers, have microstructure channels inside. Due to their special internal structure and flexible characteristics, they can be widely used in the detection of biological and chemical trace samples.
[0004] At present, gold and silver nanoparticles are widely used in Raman detection as common SERS substrates. At the same time, some new two-dimensional nanomaterials such as graphene oxide can be combined with nanoparticles to form a composite SERS substrate due to their special internal structure, which can greatly enhance the SERS detection effect. Summary of the invention
[0005] The purpose of the present invention is to solve the problems of expensive, cumbersome and time-consuming novel coronavirus detection methods, and propose a novel coronavirus Raman sensor based on an integrated optofluidic microstructure optical fiber and a SERS substrate for rapid detection, especially a Raman sensor based on a microstructure optical fiber, with nanosilver / nanographene oxide / nanogold particles functionalized with ACE2 as a special SERS substrate, which can specifically bind to SARS-CoV-2 and has a flow sampling function. The proposed sensor has the advantages of both Raman sensors and optical fiber sensors, and has the advantages of high sensitivity, fast response speed, small sample consumption, strong anti-interference ability, and flow sampling.
[0006] The present invention is achieved in that:
[0007] An integrated Raman sensor based on optofluidic microstructured optical fiber and SERS substrate includes: an optical path, a SERS substrate, a Raman detection system, a flow sampling system, etc. The optical path is composed of a light source of a portable Raman spectrometer, a hollow optical fiber with a suspended core and a microstructure channel inside; the SERS substrate is constructed by chemically bonding the surface of the suspended core grown inside the hollow optical fiber; the Raman detection system includes a spectral detection device of a portable Raman spectrometer and Raman spectral analysis software; and the flow sampling function is realized by a micro-injection pump.
[0008] The preparation process of the optofluidic Raman sensor for detecting the novel coronavirus of the present invention comprises the following steps:
[0009] 1. Preparation of nano silver sol by sol-gel method: First, dissolve 30 mg of silver nitrate in 100 mL of deionized water and heat. Secondly, dissolve 20 mg of sodium citrate in 2 mL of deionized water to make a sodium citrate solution. When the silver nitrate solution is heated to boiling, slowly add the sodium citrate solution. Finally, heat with residual heat for 20 minutes, cool to room temperature, and obtain silver nanoparticles with a size of about 80 nm.
[0010] Optionally, the residual temperature heating time may be 10 to 30 minutes.
[0011] Alternatively, 20 mg of sodium citrate was dissolved in 3 mL of deionized water.
[0012] 2. Chemical bonding method to connect nanographene oxide: Mix the silver nano solution in step 1 and the graphene oxide solution in a ratio of 1:10. Select single-layer nanographene oxide (GO). First, use deionized water to prepare a GO solution with a concentration of 0.5 mg / mL. Before the two solutions are mixed, the GO solution needs to be pretreated. That is, 96 mg of polyvinyl pyrrolidone (PVP) is added to 24 mL of GO solution, and dissolved in 12 mL of deionized water after centrifugation. Then, 3 mL of PVP-modified GO solution is added to 12 mL of PDDA (30 wt%) solution and KCl mixed solution to obtain PDDA functionalized graphene oxide (GO / PDDA) solution, which is dissolved in 6 mL of deionized water after centrifugation. Finally, the GO / Ag NPs SERS substrate is obtained by mixing the GO / PDDA solution and Ag NPs and stirring for 3 minutes.
[0013] Optionally, the silver nanoparticle solution is mixed with the graphene oxide solution in a ratio of 1:8.
[0014] Optionally, the GO / PDDA solution and Ag NPs are mixed and stirred for 2-5 minutes.
[0015] 3. Growth of nano-gold particles: The nano-silver / nano-graphene oxide solution in the above step 2 was mixed with the gold nano-solution in a ratio of 1:2 under the action of PVP to prepare a SERS enhanced substrate of nano-silver / nano-graphene oxide / nano-gold. 1mL of 1% PVP was mixed with 100μL of 100mM ascorbic acid and 100μL of 200mM NaOH solution. After stirring for 5 minutes, 50μL of nano-silver / nano-graphene oxide and 100μL of 2mM HAuCl4 solution were added to the above solution. And kept shaking in the dark for 3h. Finally, the mixture was centrifuged and the precipitate was dissolved in 50μL of ultrapure water to prepare a SERS substrate of nano-silver / nano-graphene oxide / nano-gold.
[0016] Optionally, the nanosilver / nanographene oxide solution is mixed with the gold nanosolution in a ratio of 1:4 under the action of PVP.
[0017] Optionally, the shaking time is maintained in the dark for 2 to 4 hours.
[0018] 4. Microstructured fiber modification: The SERS substrate composed of nanosilver / nanographene oxide / nanogold synthesized in step 3 above is grown on the surface of the suspended core in the microstructured fiber. In order to construct an intra-fiber Raman signal enhancement substrate around the suspended core, nanosilver / nanographene oxide / nanogold is fixed around the suspended core by chemical bonds. The pretreatment process of the hollow fiber is to first inject piranha solution (4 volumes of H2SO4 and 1 volume of H2O2) into MHF; then expose the hydroxyl groups (-OH) on the surface of the suspended core. Subsequently, 3-aminopropyltriethoxysilane (APTES, the volume ratio of APTES to ethanol is 1:15) is injected to form amino groups (-NH2). The amino group and the exposed hydroxyl group combine to serve as a bridge connecting nanosilver / nanographene oxide / nanogold. Finally, nanosilver / nanographene oxide / nanogold are deposited on the inner surface of MHF through the reaction between the amino group and nanosilver / nanographene oxide / nanogold. In order to grow a large number of particles to the surface of the suspended core, the last process is repeated several times. Then the fiber optic optofluidic online SERS sensing fiber was prepared after rinsing with deionized water.
[0019] Optionally, the volume ratio of H2SO4 and H2O2 in the piranha solution can be 2:1.
[0020] Optionally, the volume ratio of APTES to ethanol can be 1:10.
[0021] 5. Modification of microstructured optical fiber by receptor domain: The Raman sensor device with SERS substrate of nanosilver / nanographene oxide / nanogold grown on the surface of the suspended core in the microstructured optical fiber in step 4 above was thoroughly rinsed with deionized water and dried with N2. Subsequently, 1 μL ACE2 solution (30 pg) was passed into the microstructure channel and placed in an incubator under constant temperature and humidity conditions (25°C; 75%, w / w) for 4 hours. A Raman sensor for detecting the new coronavirus based on microstructured optical fiber and SERS integration was prepared.
[0022] Optionally, 0.5 μL of ACE2 solution (30 pg) was passed into the microstructure channel.
[0023] Optionally, the culture time in the incubator can be 2 to 5 hours.
[0024] 6. Preparation of Raman detection device: The microstructured optical fiber surface with nanosilver / nanographene oxide / nanogold particles functionalized with ACE2 as a special SERS substrate that can specifically bind to SARS-CoV-2 is etched with micropores in step 5 above, and a CO2 laser is used to etch micropores without damaging the suspension core so that the detection sample solution can flow out, thereby preparing a microfluidic Raman sensor device. At the same time, a layer of gold film is coated on the tail end of the optical fiber using an optical fiber coating machine to prepare a reflective layer, thereby constructing a reflective microfluidic Raman sensor device.
[0025] Alternatively, a fiber optic grinder may be used to grind micro-holes on the surface of the optical fiber.
[0026] Optionally, a silver or aluminum film may be plated on the tail end of the optical fiber as a reflective layer.
[0027] The present invention proposes a microfluidic online Raman sensor based on microstructured optical fiber with high sensitivity, fast response speed, low cost and simple operation. The most significant advantage is the integration and miniaturization of the device. The micro COVID-19 Raman sensor of the present invention is expected to be used in the rapid and efficient detection of COVID-19.
[0028] Compared with the prior art, the present invention has the following beneficial effects:
[0029] The present invention prepares a SERS substrate that specifically binds to the SARS-CoV-2 spike protein, and combines it with a hollow optical fiber to form an optofluidic Raman detector to achieve rapid detection of the SARS-CoV-2 spike protein. The microfluidic Raman SARS-CoV-2 spike protein sensor of the present invention has the advantages of high degree of integration, high sensitivity, fast response speed, low cost and simple operation. BRIEF DESCRIPTION OF THE DRAWINGS
[0030] Figure 1 Schematic diagram of the synthesis process of nanosilver / nanographene oxide / nanogold;
[0031] Figure 2 Schematic diagram of the process of growing nanosilver / nanographene oxide / nanogold microstructured hollow optical fiber for ACE2 modification;
[0032] Figure 3 This is a connection diagram of the various parts of the microstructured optical fiber microfluidic Raman sensor;
[0033] Figure 4 Schematic diagram of the construction process of microstructured optical fiber microfluidic Raman sensor;
[0034] Figure 5 This is the Raman spectrum of rhodamine solution detected by microstructured optical fiber microfluidic Raman sensor. DETAILED DESCRIPTION
[0035] The process of constructing a microstructured hollow optical fiber with ACE2 modified and grown nanosilver / nanographene oxide / nanogold can be found in Figure 1 and Figure 2 For the connection method of each part of the microstructured optical fiber microfluidic Raman sensor proposed in the present invention, please refer to Figure 3 , please refer to the construction process Figure 4The left side of the figure is a stereogram, and the right side is a cross-sectional view of the fiber end face. The numbers of the various parts represent: microstructured hollow fiber [1], inner wall of hollow fiber [1-1], microstructured channel of hollow fiber [1-2], hanging core of hollow fiber [1-3], ACE2-modified SERS substrate grown on the surface of hanging core [1-4], ACE2 layer in SERS substrate [1-5], graphene oxide layer in SERS substrate [1-6], silver nanoparticle layer in SERS substrate [1-7], gold nanoparticle layer in SERS substrate [1-8], sample outlet [2].
[0036] The present invention relates to a method for preparing a Raman sensor for rapid detection of novel coronavirus based on an integrated optofluidic microstructure optical fiber and a SERS substrate. The specific embodiments are as follows:
[0037] 1. Preparation of nanosilver sol by sol-gel method: First, dissolve 30 mg of silver nitrate in 100 mL of deionized water and heat it in an electric furnace. Secondly, dissolve 20 mg of sodium citrate in 2 mL of deionized water to make a sodium citrate solution. When the silver nitrate solution is heated to boiling, slowly add 0.1 mL of sodium citrate solution. After 2 minutes, slowly and gradually add the remaining sodium citrate solution to the silver nitrate solution and react for 10 minutes. Finally, turn off the power, heat with residual heat for 20 minutes, put the solution into a magnetic stirrer, stir and cool the solution to room temperature to obtain silver nanoparticles with a size of about 80 nm.
[0038] Preferably, in this embodiment, the residual heat heating time is 20 minutes.
[0039] Preferably, in this embodiment, 20 mg of sodium citrate is dissolved in 2 mL of deionized water.
[0040] 2. Chemical bonding method to connect nanographene oxide: Mix the silver nano solution in step 1 and the graphene oxide solution in a ratio of 1:10. Select single-layer nanographene oxide (GO) First, use deionized water to prepare a GO solution with a concentration of 0.5 mg / mL. Before the two solutions are mixed, the GO solution needs to be pretreated. That is, 96 mg of polyvinyl pyrrolidone (PVP) is added to 24 mL of GO solution, stirred with a magnetic stirrer for 1.5 hours, centrifuged 3 times to remove impurities and dissolved in 12 mL of deionized water. Then, 3 mL of PVP-modified GO solution is added to 12 mL of PDDA (30 wt%) solution and KCl mixed solution, and stirred for 30 minutes to obtain PDDA functionalized graphene oxide (GO / PDDA) solution, which is dissolved in 6 mL of deionized water after removing excess impurities after 2 centrifugations. Finally, the GO / Ag NPs SERS substrate is obtained by mixing the GO / PDDA solution and Ag NPs in a ratio of 10:1 and stirring for 3 minutes.
[0041] Preferably, in this embodiment, the silver nanoparticle solution and the graphene oxide solution are mixed in a ratio of 1:10.
[0042] Preferably, in this embodiment, the GO / PDDA solution and Ag NPs are mixed and stirred for 3 minutes.
[0043] 3. Growth of nano-gold particles: The nano-silver / nano-graphene oxide solution in the above step 2 was mixed with the gold nano-solution in a ratio of 1:2 under the action of PVP to prepare a SERS enhanced substrate of nano-silver / nano-graphene oxide / nano-gold. 1 mL of 1% PVP was mixed with 100 μL of 100 mM ascorbic acid and 100 μL of 200 mM NaOH solution. After stirring with a magnetic stirrer for 5 minutes, 50 μL of nano-silver / nano-graphene oxide and 100 μL of 2 mM HAuCl4 solution were added to the above solution. And kept shaking in the dark for 3 hours. Finally, the mixture was centrifuged 5 times to remove excess impurities, and the concentrated precipitate was dissolved in 50 μL of deionized water to prepare a SERS substrate of nano-silver / nano-graphene oxide / nano-gold.
[0044] Preferably, in this embodiment, the nano-silver / nano-graphene oxide solution is mixed with the gold nano-solution in a ratio of 1:2 under the action of PVP.
[0045] Preferably, in this embodiment, the shaking time in the dark is 3 hours.
[0046] 4. Microstructure fiber modification: The SERS substrate composed of nanosilver / nanographene oxide / nanogold synthesized in step 3 above is grown on the surface of the suspended core in the microstructure fiber. In order to construct the Raman signal enhancement substrate in the fiber around the suspended core, nanosilver / nanographene oxide / nanogold is fixed around the suspended core by chemical bonds. The pretreatment process of the hollow fiber is to first inject piranha solution (4 volumes of H2SO4 and 1 volume of H2O2) into MHF; in order to fully expose the hydroxyl groups (-OH) on the surface of the suspended core, the piranha solution is repeatedly passed into the hollow fiber for 3 times, and the solution stays inside for 30 minutes after each entry. Subsequently, 3-aminopropyltriethoxysilane (APTES, the volume ratio of APTES to ethanol is 1:15) is injected 4 times and each time it stays inside for 30 minutes to form amino groups (-NH2). The amino group and the exposed hydroxyl group are combined as a bridge connecting nanosilver / nanographene oxide / nanogold. The treated microstructure hollow fiber is repeatedly rinsed with deionized water and dried. Finally, through the reaction between amino groups and nanosilver / nanographene oxide / nanogold, nanosilver / nanographene oxide / nanogold were deposited on the inner surface of the MHF. In order to grow a large number of particles into the optical fiber, the last process was repeated several times. Then, the in-fiber optofluidic online SERS sensing fiber was prepared after rinsing with deionized water.
[0047] Preferably, in this embodiment, the volume ratio of H2SO4 and H2O2 in the piranha solution may be 4:1.
[0048] Preferably, in this embodiment, the volume ratio of APTES to ethanol may be 1:15.
[0049] 5. Modification of microstructured optical fiber by receptor domain: The Raman sensor device with SERS substrate of nanosilver / nanographene oxide / nanogold grown on the surface of the suspended core in the microstructured optical fiber in step 4 above was thoroughly rinsed with deionized water and dried with N2. Subsequently, 1 μL ACE2 solution (30 pg) was passed into the microstructured channel. In order to allow ACE2 to fully cover the surface of the SERS substrate, ACE2 was repeatedly passed after the first ACE2 was passed for 1 hour, and finally placed in an incubator under constant temperature and humidity conditions (25°C; 75%, w / w) for 4 hours. A Raman sensor for detecting the new coronavirus based on microstructured optical fiber and SERS integration was prepared.
[0050] Preferably, in this embodiment, 1 μL of ACE2 solution (30 pg) is passed into the microstructure channel.
[0051] Preferably, in this embodiment, the culture time in the incubator can be 4 hours.
[0052] 6. Preparation of Raman detection device: The surface of the microstructured optical fiber with nanosilver / nanographene oxide / nanogold particles functionalized with ACE2 as a special SERS substrate that can specifically bind to SARS-CoV-2 in step 5 above is subjected to micropore etching. A CO2 laser is used to etch micropores without damaging the suspension core. The micropores are 15 cm away from the tail end of the optical fiber. The sample solution can enter from the tail end and flow out from the micropores to prepare a microfluidic Raman sensor device. At the same time, a layer of gold film is coated on the tail end of the optical fiber using an optical fiber coating machine for 5 minutes to prepare a reflective layer and construct a reflective microfluidic Raman sensor device.
[0053] Preferably, in this embodiment, a CO2 laser is used to etch the microholes without damaging the suspension core.
[0054] Preferably, in this embodiment, a gold film is plated on the tail end of the optical fiber as a reflective layer.
[0055] Please refer to the Raman spectrum of rhodamine solution detected by microstructured optical fiber microfluidic Raman sensor. Figure 5 When a rhodamine solution with a concentration of 10-14M is injected, the Raman characteristic peak of rhodamine can be clearly detected. This proves that the Raman sensor based on the optofluidic microstructure optical fiber and the SERS substrate integrated type of the present invention has good sensitivity and detection ability.
[0056] The working principle of the integrated coronavirus Raman sensor based on optofluidic microstructured optical fiber and SERS substrate proposed in the present invention is as follows: the cell receptor angiotensin-converting enzyme 2 (ACE2) is modified on the surface of the suspended core of the microstructured hollow optical fiber. When the SARS-CoV-2 spike protein sample passes through the microstructured channel inside the hollow optical fiber, it can bind to the ACE2-modified composite SERS substrate on the surface of the suspended core to form a recognition and receptor binding domain (RBD) for the SARS-CoV-2 spike protein. At the same time, the evanescent field can collect the Raman signal into the suspended core. This binding domain successfully inhibits ACE2, which originally has obvious Raman characteristic peaks. The SARS-CoV-2 spike protein RBD targets the short β5 and β6 chains, α4 and α5 helices and loops on ACE2, which are rich in phenylalanine and amide III for CN stretching and NH bending. The SERS signal intensity quenching phenomenon will appear in the entire spectrum.
[0057] Gold and silver nanoparticles are widely used as common SERS enhancement substrates. Their Raman enhancement principle is based on the LSPR effect. By changing the size of the particles and the spacing between the particles, their electromagnetic field can be changed, that is, the Raman enhancement effect. Synthesizing nanogold and nanosilver into a composite SERS substrate can have a stronger Raman enhancement effect than a SERS substrate composed of a single particle. At the same time, by utilizing the special structure inside the two-dimensional material graphene oxide, nanosilver and nanogold are embedded in the surface of nanographene oxide, which means that the distance between nanoparticles is greatly shortened, thereby obtaining a stronger Raman enhancement effect, which is conducive to the detection of tracer and lower concentration samples.
[0058] Since the hollow optical fiber is a purely natural optofluidic device with a suspended core and a microstructure channel inside, the test sample can flow from the microstructure channel into direct contact with the suspended core. At the same time, the suspended core can use chemical methods to grow special materials on its surface to achieve a series of sensing effects. In other words, when SARS-CoV-2 flows into the hollow optical fiber, it can contact the ACE2-modified nanosilver / nanographene oxide / nanogold SERS substrate grown on the surface of the suspended core, and the excited Raman signal is collected and transmitted to the detector through the evanescent field of the suspended core. Thus, the Raman spectrum is obtained.
Claims
1. A Raman sensor for rapid detection of novel coronavirus based on an integrated optofluidic microstructured optical fiber and a SERS substrate, characterized in that: The following steps are involved: Step 1: Preparation of nano silver sol by sol-gel method: using redox method, sodium citrate solution is added dropwise to boiling silver nitrate solution until the two solutions are completely reacted and cooled to room temperature, thereby obtaining silver nanoparticles with a size of 80 nm; Step 2, chemical bonding method to connect nano-graphene oxide: mix the silver nano-solution in step 1 with the graphene oxide solution in a ratio of 1:10; select single-layer nano-graphene oxide GO; first, use deionized water to prepare a GO solution with a concentration of 0.5 mg / mL; before the two solutions are mixed, the GO solution needs to be pretreated; that is, 96 mg of polyvinyl pyrrolidone PVP is added to 24 mL of GO solution, and the solution is dissolved in 12 mL of deionized water after centrifugation; then, 3 mL of PVP-modified GO solution is added to 12 mL of 30 wt% PDDA solution and KCl mixed solution to obtain PDDA functionalized graphene oxide GO / PDDA solution, which is dissolved in 6 mL of deionized water after centrifugation; finally, the GO / PDDA solution and AgNPs are mixed and stirred for 3 minutes to obtain a GO / AgNPs SERS substrate; Step 3, growth of nano-gold particles: the nano-silver / nano-graphene oxide solution prepared in step 2 was mixed with the gold nano-solution in a ratio of 1:2 under the action of PVP to prepare a SERS enhanced substrate of nano-silver / nano-graphene oxide / nano-gold; 1 mL of 1% PVP was mixed with 100 μL of 100 mM ascorbic acid and 100 μL of 200 mM NaOH solution; after stirring for 5 minutes, 50 μL of nano-silver / nano-graphene oxide and 100 μL of 2 mM HAuCl4 solution were added to the above solution; and the mixture was kept shaking for 3 hours in the dark; finally, the mixture was centrifuged and the precipitate was dissolved in 50 μL of ultrapure water to prepare a SERS substrate of nano-silver / nano-graphene oxide / nano-gold; Step 4, microstructure fiber modification: the SERS enhancement substrate of nanosilver / nanographene oxide / nanogold synthesized in the above step 3 is grown on the surface of the suspended core in the microstructure fiber under the action of chemical bonding, and then rinsed with deionized water to prepare an intra-fiber optofluidic online SERS sensing fiber; Step 5. Modification of the microstructured optical fiber by the receptor domain: The optical fiber in the above step 4, in which the SERS enhanced substrate of nanosilver / nanographene oxide / nanogold is grown on the surface of the suspended core of the microstructured optical fiber, is thoroughly rinsed with deionized water and dried with N2, and then the ACE2 solution is passed through and allowed to stand for 3 hours to prepare a Raman sensor for detecting the new coronavirus based on microstructured optical fiber and SERS integration; Step 6. Preparation of Raman detection device: The nanosilver / nanographene oxide / nanogold particles functionalized with ACE2 in step 5 above are used as micro-holes on the surface of the microstructured optical fiber and SERS integrated Raman sensor for detecting the new coronavirus that can specifically bind to SARS-CoV-2. A CO2 laser is used to etch micropores without damaging the suspension core so that the detection sample solution can flow out, thereby preparing a microfluidic Raman sensor device.
2. According to claim 1, a Raman sensor for rapid detection of novel coronavirus based on integrated optofluidic microstructured optical fiber and SERS substrate, characterized in that: A natural optofluidic microstructure optical fiber, which has a suspended core and a microstructure channel inside, can realize online monitoring of trace samples; at the same time, this optical fiber is conducive to device integration and miniaturization.
3. According to claim 1, a Raman sensor for rapid detection of novel coronavirus based on an integrated optofluidic microstructured optical fiber and a SERS substrate, characterized in that: In this microstructured optical fiber, the prepared nanosilver / nanographene oxide / nanogold is grown on the surface of the suspended core by chemical bonding method to form an optofluidic Raman sensor device with Raman enhancement effect.
4. According to claim 1, a Raman sensor for rapid detection of novel coronavirus based on integrated optofluidic microstructured optical fiber and SERS substrate, characterized in that: The microstructure channel inside the sensor can allow the sample solution to flow in from one end and out from the surface micropores, so it has a flow injection function and realizes an optofluidic Raman sensor device.
5. According to claim 1, a Raman sensor for rapid detection of novel coronavirus based on integrated optofluidic microstructured optical fiber and SERS substrate, characterized in that: The construction of this kind of nanosilver / nanographene oxide / nanogold particles functionalized with ACE2 as a special SERS substrate can specifically bind to SARS-CoV-2, eliminate external interference, and has high sensitivity and rapid detection characteristics.