A fiber-optic biosensor for detecting ab42 and a method for preparing the same

Abstract

The application discloses a kind of detection A beta 42 optical fiber biosensor and preparation method thereof, belong to optical fiber biosensor technical field, including the following steps: S1, using seedless growth method preparation gold nano triangle piece, and through HS-PEG-COOH ligand replacement;S2, after removing the coating of single-mode optical fiber matrix to be processed region, it is washed, using optical fiber fusion machine to single-mode optical fiber matrix is handled to pull cone, then through CO2 laser periodic effect, form TLPG sensor;S3, TLPG sensor is modified with surface silanization, gold nano triangle piece is loaded, carboxyl activation and antibody fixation, obtain optical fiber biosensor;The application utilizes the unique tip electric field enhancement of gold nano triangle piece and the evanescent field enhancement effect of micro-taper long-period fiber grating synergistic effect, realizes the high sensitivity, rapid detection to A beta 42.

Description

Technical Field

[0001] This invention belongs to the field of fiber optic biosensor technology, specifically relating to a fiber optic biosensor for detecting Aβ42 and its preparation method. Background Technology

[0002] Alzheimer's disease (AD) is a serious neurodegenerative disease, and early diagnosis is crucial for slowing disease progression and improving patients' quality of life. β-amyloid 1-42 (Aβ42) is a recognized core biomarker for AD, and developing highly sensitive, highly specific, rapid, and convenient Aβ42 detection methods is currently a hot research topic.

[0003] Existing methods for Aβ42 detection, such as enzyme-linked immunosorbent assay (ELISA), electrochemical analysis, and fluorescence analysis, generally suffer from drawbacks such as cumbersome operation, long processing time, and reliance on expensive equipment. Fiber optic biosensors, with their advantages of interference resistance, small size, and remote monitoring capabilities, have become an ideal alternative. Among them, fiber optic sensors based on localized surface plasmon resonance (LSPR) can significantly amplify signals by modifying the fiber surface with noble metal nanomaterials. Gold nanospheres and gold nanorods are commonly used nanomaterials in existing technologies, but the electric field enhancement effect of gold nanospheres is limited, and the preparation of gold nanorods using a seed method involves multiple steps, long processing time, and large batch-to-batch variations, also resulting in limited electric field enhancement effects and restricting their application in practical sensor fabrication.

[0004] Therefore, how to develop a high-performance fiber optic biosensor for detecting Aβ42 based on nanomaterial-enhanced sensitization is a technical problem that urgently needs to be solved. Summary of the Invention

[0005] The purpose of this invention is to provide a fiber optic biosensor for detecting Aβ42 and its preparation method. A seedless growth method is used to synthesize uniform, sharp-tipped gold nanotriangles in one step. These nanotriangles are then efficiently loaded onto the surface of a microconical long-period fiber grating via Au-S bonds. Utilizing the unique tip electric field enhancement effect of the gold nanotriangles, combined with the evanescent field enhancement of the microconical grating, a dual sensitization mechanism is achieved, resulting in excellent detection performance for Aβ42. This overcomes the technical problems of insufficient sensitivity, long detection cycle, limited LSPR enhancement effect of nano-sensitizing materials in existing fiber optic sensors, and cumbersome and unstable preparation processes.

[0006] The objective of this invention can be achieved through the following technical solutions: A method for preparing an optical fiber biosensor for detecting Aβ42 includes the following steps: S1. Preparation and carboxylation of gold nanotriangles: Gold nanotriangles were prepared by seedless growth method and ligand replacement was performed by mercaptopolyethylene glycol carboxylic acid (HS-PEG-COOH) to obtain a carboxyl-modified gold nanotriangle dispersion. S2. Fabrication of Micro-tapered Long Period Fiber Grating (TLPG): After removing the coating layer from the area to be processed of the single-mode fiber substrate and cleaning it, it is then mounted on a fiber fusion splicer for tapering to form a micro-tapered fiber (T-SMF). The tapered region is periodically treated with CO2 laser to form a TLPG sensor. S3. Preparation of fiber optic biosensor: The TLPG sensor obtained in step S2 was subjected to surface cleaning and hydroxyl activation treatment. After cleaning and drying, it was immersed in a 3-mercaptopropyltrimethoxysilane (MPTMS) ethanol solution for silanization modification to introduce thiol functional groups on its surface. After cleaning, it was immersed in the carboxyl-modified gold nanotriangle dispersion obtained in step S1. The gold nanotriangles were fixed to the surface of the fiber optic sensing area through Au-S covalent bonds. After removal, it was immersed in an EDC / NHS mixed solution for activation treatment to fully activate the carboxyl groups on the surface of the gold nanotriangles. Then, it was immersed in an Aβ42 monoclonal antibody PBS solution to fix the Aβ42 monoclonal antibody to the surface of the gold nanotriangles through covalent bonds. Finally, it was washed with PBS buffer to remove unbound free antibody, thus obtaining the fiber optic biosensor.

[0007] Furthermore, the seedless growth method for preparing gold nano-triangular sheets described in step S1 specifically includes the following steps: First, hexadecyltrimethylammonium bromide (CTAC) solution was added to deionized water, followed by potassium iodide (KI) solution, then chloroauric acid (HAuCl4) solution and a portion of NaOH solution. The mixture was then thoroughly mixed, followed by rapid addition of ascorbic acid solution and thorough mixing. Finally, the remaining NaOH solution was added and rapidly stirred for 2-3 seconds. After standing, the mixture was centrifuged and washed. The washed precipitate was then added to deionized water and ultrasonically dispersed to obtain a gold nanotriangular sheet solution. Under the synergistic guiding effect of hexadecyltrimethylammonium bromide and potassium iodide, ascorbic acid reduced chloroauric acid to form gold nanotriangular sheets. Iodide ions effectively improved the yield of triangular sheet morphology through selective adsorption and oxidative etching.

[0008] Further, the volume ratio of the CTAC solution, KI solution, HAuCl4 solution, NaOH solution, ascorbic acid solution, and deionized water is 6.4 mL: 300 μL: 320 μL: 122 μL: 320 μL: 32 mL; the concentration of the CTAC solution is 0.1 M; the concentration of the KI solution is 0.01 M; the concentration of the HAuCl4 solution is 25.5 mM; the concentration of the NaOH solution is 0.1 M; and the concentration of the ascorbic acid solution is 64 mM; wherein the NaOH solution is added in two separate applications at a volume ratio of 2:1. By precisely controlling the amount and order of addition of NaOH, anisotropic nucleation and growth of gold nanotriangular sheets are achieved.

[0009] Furthermore, the ligand replacement in step S1 includes the following steps: HS-PEG-COOH solution was added to the gold nanoparticle triangular sheet solution and stirred at room temperature for 12 h to carry out ligand replacement, so that the thiol ligand gradually replaced the CTAC molecules on the surface of the gold nanoparticle triangular sheet to form a stable Au-S covalent bond, which provides a reaction site for subsequent antibody conjugation. After the reaction was completed, the unreacted excess ligand was removed by centrifugation and washing. The precipitate was redispersed in deionized water to obtain a carboxyl-modified gold nanoparticle triangular sheet dispersion.

[0010] Furthermore, the volume ratio of the gold nanoparticle triangular sheet solution, the HS-PEG-COOH solution, and the deionized water is 1:1:2, the concentration of the gold nanoparticle triangular sheet solution is 1 mg / mL, and the concentration of the HS-PEG-COOH solution is 0.01 g / mL.

[0011] Further, the hydroxyl activation treatment in step S3 involves immersing the sensing area of ​​the TLPG sensor in a piranha solution for 0.5 hours.

[0012] Furthermore, in step S3, the volume fraction of the MPTMS ethanol solution is 15%, and the soaking time is 5 hours.

[0013] Further, in step S3, the concentrations of EDC and NHS in the EDC / NHS mixed solution are 12 mM and 30 mM, respectively, and the activation treatment time is 30 min.

[0014] Furthermore, in step S3, the concentration of the Aβ42 antibody PBS solution is 50 μg / mL, the soaking reaction temperature is 4°C, and the reaction time is 30 min.

[0015] A fiber optic biosensor for detecting Aβ42 is fabricated using the method described above. The fiber optic biosensor comprises: a single-mode fiber substrate, a microconical long-period fiber grating formed in the sensing region of the single-mode fiber substrate, a gold nanoparticle triangular layer fixed to the surface of the microconical long-period fiber grating, and an Aβ42 monoclonal antibody recognition layer fixed to the surface of the gold nanoparticle triangular layer. The microconical long-period fiber grating enhances evanescent field and intermodal coupling. The gold nanoparticle triangular layer is fabricated using a seedless growth method and has sharp triangular apex angles, which are used to generate a strong LSPR effect under photoexcitation, amplifying the optical signal changes caused by surface antibody-antigen binding events. The Aβ42 monoclonal antibody recognition layer specifically captures the Aβ42 antigen.

[0016] The beneficial effects of this invention are: Compared with the traditional seeded method, the seedless growth method adopted in this invention does not require the pre-preparation and aging of gold seeds. All reactions are completed sequentially in one pot, with fewer operation steps, shorter total time, and reduced instability caused by batch differences in seed quality. It also has a higher morphological yield and is more suitable for the standardization and large-scale application of sensor fabrication. The gold nanotriangular plates of this invention provide a significantly stronger local electric field enhancement through the lightning rod effect generated by their sharp apex. Simulation results clearly show that the electric field intensity at the sharp corners of the triangular plates is far greater than that of spherical particles, and the coexistence of multiple triangular plates also generates coupling enhancement, laying a physical foundation for ultra-high sensitivity detection. The extreme LSPR enhancement of the gold nanotriangular plates combined with the evanescent field enhancement of the microconical long-period fiber grating achieves highly sensitive and rapid detection of Aβ42, with good linearity in the concentration range of 25-300 ng / mL, a detection sensitivity of 3.9 pm / (ng / mL), a theoretical detection limit as low as 15.4 ng / mL, and a response time of only 4 min. The overall performance is significantly better than most existing Aβ42 detection methods. Attached Figure Description

[0017] The present invention will now be further described with reference to the accompanying drawings.

[0018] Figure 1 This is a transmission electron microscope image of the gold nanotriangular sheet prepared in Example 1 of the present invention; Figure 2 This is a physical image of the gold nano-triangular sheet solution prepared in Example 1 of the present invention; Figure 3 This is a schematic diagram of the structure of the TLPG sensor obtained in Embodiment 2 of the present invention; Figure 4 This is a SEM image of the fiber optic biosensor prepared in Example 3 of the present invention at a magnification of 90k×. Figure 5These are near-field intensity distribution diagrams of the TLPG sensor (a) prepared in Example 2 of the present invention, the optical fiber biosensor (c) and (d) prepared in Comparative Example 1, and Example 3. Figure 6 This is a linear fitting diagram of the resonant peak wavelength of the TLPG sensor prepared in Example 2 of the present invention in NaCl solutions with different refractive indices; Figure 7 This is a linear fitting diagram of the resonant peak wavelength of the fiber optic biosensor prepared in Example 3 of the present invention in NaCl solutions with different refractive indices. Figure 8 This is a linear fitting diagram of the resonant peak wavelength of the fiber optic biosensor prepared in Example 3 of the present invention in Aβ42 solutions of different concentrations; Figure 9 This is a comparison of the resonant peak wavelength shift of the fiber optic biosensor prepared in Example 3 of the present invention in solutions of Aβ42, BSA, IgG, HSA, and HFg. Figure 10 This is a scatter plot showing the change in wavelength shift of the resonant peak of the fiber optic biosensor prepared in Example 3 of the present invention over time in Aβ42 solution. Detailed Implementation

[0019] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0020] Example 1

[0021] This embodiment provides a carboxyl-modified gold nanoparticle triangular sheet dispersion, which is prepared through the following steps: A) Seedless growth: Add 6.4 mL of 0.1 M CTAC solution to 32 mL of deionized water, then add 300 μL of 0.01 M KI solution, followed by 320 μL of 25.5 mM HAuCl4 solution and 82 μL of 0.1 M NaOH solution. Mix thoroughly to obtain a light yellow solution. Then, quickly add 320 μL of 64 mM ascorbic acid solution and mix thoroughly. The solution color gradually changes from light yellow to colorless. Finally, add 40 μL of 0.1 M NaOH solution and stir rapidly for 2-3 seconds. After standing, centrifuge to separate the precipitate and wash with deionized water. Then, add deionized water and sonicate to disperse, preparing a 1 mg / mL gold nanoparticle triangular sheet solution. Figure 2 As shown, the gold nanoparticle triangular sheet solution is blue; from Figure 1As can be seen, the gold nanotriangular pieces are generally regular triangular in shape with clear edge contours, indicating that the gold nanotriangular pieces have good morphological consistency. Combined with the scale bar in the figure, it can be seen that its feature size is about 60 nm. B) Ligand substitution and carboxylation: 1 mL of 0.01 g / mL HS-PEG-COOH solution was added to 1 mL of gold nanotriangular sheet solution, and the mixture was stirred at room temperature for 12 h to carry out the ligand substitution reaction. After the reaction was completed, the mixture was separated and washed by centrifugation at 8000 rpm, and then redispersed in 2 mL of deionized water to obtain a carboxyl-modified gold nanotriangular sheet dispersion.

[0022] Example 2

[0023] This embodiment provides a TLPG sensor, which is manufactured by the following steps: After removing the coating layer from the area to be processed of the single-mode fiber substrate, it is cleaned and then installed on an LZM-100 fiber fusion splicer for tapering treatment to form a T-SMF with a tapered area diameter of 22μm. The tapered area is then moved to the CO2 laser action area, and the tapered area is periodically acted on by the CO2 laser to form a series of periodic microcones on the surface of the tapered area, thereby obtaining the TLPG sensor. Depend on Figure 3 (a) The T-SMF and its conical structure can be seen, formed by... Figure 3 (b) It can be seen that the overall structure of the TLPG sensor is composed of... Figure 3 (c) It can be seen that after introducing periodic microcones on the basis of T-SMF, a clear and distinguishable periodic structure is formed on the surface of the cone region. The diameter of the T-SMF cone region is reduced from 21.41 μm to 20.27 μm, and the interval between the two microcones is 402.57 μm, indicating that the TLPG sensor has been successfully fabricated.

[0024] Example 3

[0025] This embodiment provides a fiber optic biosensor, which is prepared by the following steps: The TLPG sensor prepared in Example 2 was washed sequentially with acetone and deionized water. Then, the sensing area of ​​the TLPG sensor was activated by immersing it in piranha solution for 0.5 h to activate the hydroxyl groups on the surface of the sensing area. After washing with deionized water, it was dried in air for 0.5 h, and then immersed in a 15% (v / v) MPTMS ethanol solution for 5 h. After the reaction, unbound MPTMS was washed away with ethanol, and then immersed in 2 mL of the carboxyl-modified gold nanotriangular sheet dispersion prepared in Example 1 for 6 h. After removal, it was activated by immersing in a mixed solution containing 12 mM EDC and 30 mM NHS for 30 min. After removal, it was immersed in a 50 μg / mL Aβ42 monoclonal antibody PBS solution and reacted at 4 °C for 30 min. After the reaction, it was washed with PBS buffer for 15 min to obtain the fiber optic biosensor.

[0026] from Figure 4 As can be seen, the gold nanoparticles are uniformly distributed on the surface of the TLPG sensor, indicating that the gold nanoparticles have been successfully grown in the TLPG sensing region through the above surface modification method.

[0027] Comparative Example 1 The difference between this comparative example and Example 3 is that the carboxyl-modified gold nanosphere dispersion prepared in Example 1 is replaced by an equal amount of carboxyl-modified gold nanotriangular sheet dispersion, while the other raw materials and steps are the same.

[0028] Depend on Figure 5 (a) It can be seen that when no metal nanoparticles are introduced, the electric field distribution in the calculation area of ​​the TLPG sensor is relatively uniform and no obvious local enhancement region appears. This indicates that when relying solely on the fiber body structure, although there is a certain evanescent field near the surface, the overall field enhancement effect is limited. Figure 5 (b) It can be seen that, in Comparative Example 1, after the introduction of gold nanospheres, a certain degree of local electric field enhancement occurs around them, indicating that the gold nanospheres can excite local surface plasmon resonance under the action of incident light; however, this enhancement is mainly limited to the vicinity of the particles, and the overall enhancement effect is relatively weak; Figure 5 (c) It can be seen that a significant high-field concentration phenomenon is observed at the three sharp corners of a single gold nanotriangular sheet, indicating that compared with spherical gold nanoparticles, gold nanotriangular sheets are more likely to form a local strong electric field at the sharp corners, thus exhibiting a stronger local field enhancement capability; Figure 5(d) The electric field distribution when multiple gold nanotriangles coexist can be directly observed. It can be seen that, in addition to the significant electric field enhancement at the sharp corners of each gold nanotriangle, a certain degree of near-field coupling occurs between the particles, further expanding the local field enhancement region. Compared to a single gold nanotriangle, the overall field enhancement effect is more significant when multiple particles are distributed together. This indicates that forming a certain density of gold nanotriangles on the fiber surface can further improve the local electric field strength of the sensing area, thereby enhancing the sensor's response to changes in the external dielectric environment. From the sensing mechanism perspective, the wave vector shift caused by changes in the external dielectric environment is directly related to the degree of electric field overlap within the sensing area.

[0029] The sensors prepared in Examples 2 and 3 were subjected to performance testing, and the testing methods are as follows: The fiber optic sensor is fixed to the support platform, and UV glue is used to fix both ends of the sensor to reduce the impact of external vibration and environmental disturbance. An adjustable lifting platform is set below the sensing area to place the liquid to be tested. By adjusting the height of the lifting platform, the sensing area is stably immersed in the liquid to be tested, and the immersion depth remains basically consistent in each test. The sensor input is connected to a broadband light source, and the output is connected to a spectrometer to monitor the change of the center wavelength of the resonance peak of the transmission spectrum in real time.

[0030] Test Example 1 In this test example, NaCl solution was selected as the test liquid. The linear fitting results of the resonant peak wavelengths of the sensing regions of the TLPG sensor (bare optical fiber) prepared in Example 2 and the optical fiber biosensor prepared in Example 3 in NaCl solutions with different refractive indices were tested. The results are as follows: Figure 6 and Figure 7 As shown; from Figure 6 As can be seen, with the increase of the refractive index of the NaCl solution, the resonance peak shifts towards longer wavelengths, exhibiting a significant redshift. When the refractive index of the NaCl solution is 1.33249, the resonance wavelength is 1401.20 nm; when the refractive index of the NaCl solution is 1.33869, the resonance wavelength is 1403.20 nm, a redshift of 2.0 nm. R1 2 The value >0.996 indicates a good linear relationship in the fitting results, and the center wavelength of the resonance peak shifts to the right as the external refractive index increases. The refractive index sensitivity S of the TLPG sensor is... R1 It is 316.0 nm / RIU.

[0031] Depend on Figure 7It can be seen that as the refractive index of the NaCl solution increases, the resonance peak shifts towards longer wavelengths, exhibiting a significant redshift. When the refractive index of the NaCl solution is 1.33287, the resonant wavelength is 1402.87 nm; when the refractive index of the NaCl solution is 1.33661, the TLPG resonant wavelength is 14015.4 nm, a redshift of 2.26 nm. Compared with Example 2, the sensor in Example 3 exhibits a more significant wavelength shift within the same refractive index variation range. 2 The value >0.996 indicates a good linear relationship in the fitting results, suggesting that the refractive index sensitivity of the fiber optic biosensor prepared in Example 3 reaches 601.2 nm / RIU.

[0032] Test Example 2 In this test example, Aβ42 solution was selected as the test liquid. Different concentrations of Aβ42 sample solutions were sequentially brought into contact with the sensing area. As Aβ42 specifically binds to the antibody on the sensor surface, a linear fitting result of the resonant peak wavelength was formed, as shown in the figure. Figure 8 As shown; Depend on Figure 8 It can be seen that as the concentration of Aβ42 gradually increases, the resonance peak of the sensor in Example 3 continuously shifts towards longer wavelengths, exhibiting a significant redshift trend. This indicates that as the concentration of the target protein increases, the amount of antigen and antibody binding on the sensor surface continuously increases, thereby causing a change in the local refractive index of the sensing region, which ultimately manifests as a shift in the resonance wavelength. Within the concentration range of 25-300 ng / mL, there is a good correlation between the increase in Aβ42 concentration and the redshift of the resonance peak, with a detection sensitivity of 3.9 pm / (ng / mL). Furthermore, the linear fit is good, and the correlation coefficient satisfies R0. 2 >0.994. Typically, the theoretical detection limit of a sensor can be expressed as... Based on the resolution of the spectrometer used in this experiment and the sensitivity obtained through fitting, the detection limit of the fiber optic biosensor prepared in Example 3 for Aβ42 can be calculated to be 15.4 ng / mL. The test results show that this sensor can effectively detect low concentrations of Aβ42 protein and has good application potential in the analysis of early biomarkers for Alzheimer's disease.

[0033] Test Example 3 In this test example, bovine serum albumin (BSA), human immunoglobulin (IgG), human serum albumin (HSA), and human fibrinogen (HFg) solutions were selected as interfering agents. The wavelength shift of Aβ42 was compared with that of Aβ42 at a concentration of 300 ng / mL to test the specificity of the fiber optic biosensor prepared in Example 3 for Aβ42. The results are as follows: Figure 9 As shown; Depend on Figure 9It can be seen that the wavelength drift of the fiber optic biosensor prepared in Example 3 when interacting with Aβ42 reaches 1.12 nm, while the wavelength drift when interacting with interfering substances BSA, IgG, HSA, and HFg is very small, indicating that the sensor meets the purpose of specific detection.

[0034] Test Example 4 To evaluate the sensor's responsiveness, this test example investigated the variation trend of the resonant wavelength drift of the fiber optic biosensor prepared in Example 3 under a concentration of 300 ng / mL Aβ42. The results are as follows: Figure 10 As shown; Depend on Figure 10 It can be seen that as the Aβ42 antibody on the sensor surface specifically reacts with the Aβ42 antigen, the change in the sensor's resonant wavelength drift tends to stabilize, indicating that the sensor reaction gradually slows down and eventually stops, remaining stable after 4 minutes. This suggests that the biosensor has a response time of 4 minutes, which is relatively short and beneficial for its practical application in disease detection.

[0035] It should be noted that, in this document, relational terms such as "first" and "second" are used only to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, method, article, or apparatus.

[0036] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A method for preparing an optical fiber biosensor for detecting Aβ42, characterized in that, Includes the following steps: S1. Gold nano-triangular sheets were prepared by seedless growth method and ligand replacement was performed by HS-PEG-COOH to obtain a carboxyl-modified gold nano-triangular sheet dispersion. S2. After removing the coating layer from the area to be processed of the single-mode fiber substrate, clean it and then install it on the fiber fusion splicer for tapering to form a micro-tapered fiber. The tapered area is periodically treated with CO2 laser to form a TLPG sensor. S3. The TLPG sensor is surface cleaned and hydroxyl activated. After cleaning and drying, it is immersed in MPTMS ethanol solution for silanization modification. After cleaning, it is immersed in the carboxyl-modified gold nanoparticle dispersion. After removal, it is immersed in EDC / NHS mixed solution for activation treatment. Then it is immersed in Aβ42 monoclonal antibody PBS solution. Finally, it is washed with PBS buffer to obtain the fiber optic biosensor.

2. The method for preparing an optical fiber biosensor for detecting Aβ42 according to claim 1, characterized in that, The seedless growth method for preparing gold nano-triangular sheets specifically includes the following steps: First, add CTAC solution to deionized water, then add KI solution, followed by HAuCl4 solution and a portion of NaOH solution and mix thoroughly. Then, quickly add ascorbic acid solution and mix thoroughly. Finally, add the remaining NaOH solution and stir rapidly. After standing, centrifuge and wash. Add the washed precipitate to deionized water and sonicate to disperse, thus obtaining a gold nanoparticle triangular sheet solution.

3. The method for preparing an optical fiber biosensor for detecting Aβ42 according to claim 2, characterized in that, The volume ratio of CTAC solution, KI solution, HAuCl4 solution, NaOH solution, ascorbic acid solution, and deionized water is 6.4 mL: 300 μL: 320 μL: 122 μL: 320 μL: 32 mL; the concentration of CTAC solution is 0.1 M; the concentration of KI solution is 0.01 M; the concentration of HAuCl4 solution is 25.5 mM; the concentration of NaOH solution is 0.1 M; and the concentration of ascorbic acid solution is 64 mM; wherein, the NaOH solution is added in two portions at a volume ratio of 2:

1.

4. The method for preparing an optical fiber biosensor for detecting Aβ42 according to claim 1, characterized in that, The ligand replacement includes the following steps: HS-PEG-COOH solution was added to the gold nanotriangular sheet solution, and the mixture was stirred at room temperature for 12 h to carry out ligand replacement. After the reaction was completed, the mixture was centrifuged and washed, and the precipitate was redispersed in deionized water to obtain a carboxyl-modified gold nanotriangular sheet dispersion.

5. The method for preparing an optical fiber biosensor for detecting Aβ42 according to claim 4, characterized in that, The volume ratio of the gold nanoparticle triangular sheet solution, the HS-PEG-COOH solution, and the deionized water is 1:1:

2. The concentration of the gold nanoparticle triangular sheet solution is 1 mg / mL, and the concentration of the HS-PEG-COOH solution is 0.01 g / mL.

6. The method for preparing an optical fiber biosensor for detecting Aβ42 according to claim 1, characterized in that, The hydroxyl activation treatment involves immersing the sensing area of ​​the TLPG sensor in a piranha solution for 0.5 hours.

7. The method for preparing an optical fiber biosensor for detecting Aβ42 according to claim 1, characterized in that, The MPTMS ethanol solution had a volume fraction of 15% and a soaking time of 5 hours.

8. The method for preparing an optical fiber biosensor for detecting Aβ42 according to claim 1, characterized in that, The concentrations of EDC and NHS in the EDC / NHS mixed solution are 12 mM and 30 mM, respectively, and the activation treatment time is 30 min.

9. The method for preparing an optical fiber biosensor for detecting Aβ42 according to claim 1, characterized in that, The concentration of the Aβ42 antibody in the PBS solution was 50 μg / mL, the soaking reaction temperature was 4℃, and the reaction time was 30 min.

10. A fiber optic biosensor for detecting Aβ42, characterized in that, It is prepared by the preparation method according to any one of claims 1-9.

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