A silicon nanowire field effect transistor biosensor and a preparation method and application thereof

Abstract

The application provides a silicon nanowire field effect transistor biosensor and a preparation method and application thereof. 1‑42 The PBS solution of the nucleic acid aptamer contains A 1‑42 The base sequence of the nucleic acid aptamer is 5'-NH2-(CH2)4-UAGCGUAUGCCACUCUCCUGGGACCCCCCGCCGGAUGGCCACAUCC-3'. S3, performing surface functionalization treatment on the silicon nanowire of the silicon nanowire field effect transistor sensor; S4, placing the silicon nanowire of the silicon nanowire field effect transistor sensor in an anhydrous ethanol solution containing 3-aminopropyl triethoxysilane to perform condensation reaction, then cleaning and heating with anhydrous ethanol after the condensation reaction is completed, and finally adding the PBS solution containing A 1‑42 The PBS solution of the nucleic acid aptamer contains A 1‑42 The nucleic acid aptamer can detect A 1‑42 This characteristic biomarker can realize rapid, accurate and high-sensitivity detection.

Description

Technical Field

[0001] This invention relates to the field of biosensor technology, specifically to a silicon nanowire field-effect transistor biosensor, its fabrication method, and its application. Background Technology

[0002] Alzheimer's disease is the most common neurodegenerative disease.

[0003] Although early diagnosis and treatment of Alzheimer's disease are crucial, current treatment methods are still in their early stages, lacking effective drugs or treatment strategies to prevent or slow disease progression. Most Alzheimer's patients are diagnosed in the middle or late stages of the disease, missing the optimal window for early intervention and thus exacerbating the disease burden.

[0004] Given that there are currently no effective drugs to prevent or significantly slow the progression of Alzheimer's disease, early diagnosis and intervention are particularly important. Biomarkers, as a key tool, can reveal the stage-specific abnormal biological and pathological processes of Alzheimer's disease. According to the amyloid-beta (Aβ) toxicity hypothesis, the physiological and pathological mechanisms of Alzheimer's disease are closely related to Aβ. Aβ formation is the product of cleavage of Aβ precursor proteins by β-secretase and γ-secretase. Different cleavage sites by γ-secretase yield Aβ with different numbers of amino acids. 1-42 It is considered a hallmark biomarker of Alzheimer's disease. Early identification of Aβ. 1-42 The deposition of these deposits is crucial for the early detection and intervention of Alzheimer's disease.

[0005] Currently, there are several methods for using Aβ. 1-42 While methods like positron emission tomography (PET) and cerebrospinal fluid analysis can be used for detection, these methods are generally costly, complex, and require specialized equipment, making them difficult to widely implement in primary healthcare settings. Furthermore, traditional immunoassay methods (such as enzyme-linked immunosorbent assay, immunofluorescence chromatography, immunoprecipitation mass spectrometry, and colloidal gold methods) can effectively detect Aβ. 1-42 However, these methods generally suffer from low sensitivity, high cost, and cumbersome operation. In many cases, irreversible cognitive decline has already occurred by the time the disease is detected, which severely affects the effectiveness of interventions for Alzheimer's disease.

[0006] To overcome these challenges, nucleic acid aptamer-based biosensor technology has offered a novel approach to the detection of Alzheimer's disease biomarkers in recent years. Nucleic acid aptamers, as highly specific and affinity single-stranded oligonucleotide molecules, can specifically bind to target molecules. Combining nucleic acid aptamers with semiconductor sensor technology enables real-time, label-free, and highly sensitive monitoring of Alzheimer's disease biomarkers. This method allows for sensitive detection of target molecules at relatively low concentrations, overcoming the limitations of traditional detection methods and offering significant advantages in sensitivity and cost. However, these sensors are susceptible to non-specific adsorption on the device surface and the Debye shielding effect during actual detection, limiting accuracy and sensitivity. Optimization of the device structure and modification methods is necessary to overcome these limitations. Summary of the Invention

[0007] To address the shortcomings of existing technologies, this invention provides a silicon nanowire field-effect transistor biosensor, its fabrication method, and its applications, which utilizes specific nucleic acid aptamers with Aβ... 1-42 The specific binding of silicon nanowires enables biosensors to achieve highly sensitive detection through changes in the electrical signals of silicon nanowire field-effect transistors, thus solving the problems mentioned in the background art.

[0008] To achieve the above objectives, the present invention provides the following technical solution:

[0009] According to a first aspect of the present invention, a method for fabricating a silicon nanowire field-effect transistor biosensor is provided, comprising the following steps:

[0010] S1. Fabrication of silicon nanowire field-effect transistor sensors;

[0011] S2, Configuration containing Aβ 1-42 PBS solution of nucleic acid aptamers, wherein the Aβ 1-42 The base sequence of the nucleic acid aptamer is: 5'-NH2-(CH2)4-UAGCGUAUGCCACUCUCCUGGGACCCCCCGCCGGAUGGCCA-CAUCC-3';

[0012] S3. Surface functionalization treatment of silicon nanowires in silicon nanowire field-effect transistor sensors.

[0013] S4. The silicon nanowires of the silicon nanowire field-effect transistor sensor are placed in an anhydrous ethanol solution containing 3-aminopropyltriethoxysilane for a condensation reaction. After the condensation reaction is complete, the mixture is washed with anhydrous ethanol, heated, and finally the solution containing Aβ is added dropwise. 1-42 The PBS solution of the nucleic acid aptamer was allowed to stand for 2-4 hours and then stored at 4°C for later use.

[0014] Preferably, in step S1, the silicon nanowire field-effect transistor sensor is fabricated as follows:

[0015] S1-1. Define a rectangular photoresist pattern on the surface of the SiO2 layer of a SiO2 / n-type heavily doped silicon substrate using photolithography.

[0016] S1-2. Using inductively coupled plasma etching technology, C4F8 and O2 plasmas are used alternately to etch the SiO2 layer to obtain a multi-level guided step structure. Then, the layer is ultrasonically treated in acetone, ethanol and deionized water in sequence to remove the photoresist on the surface.

[0017] S1-3. Electron beam evaporation is used to deposit indium strips on the surface of the multi-level guided step structure. Then, annealing is performed to reduce the indium oxide strips and condense them into catalytic indium droplets. Then, SiH4 gas is introduced to deposit an amorphous silicon film on the surface of the guided step structure. Finally, the indium droplets are activated to absorb the pre-coated amorphous silicon film, and then etched to obtain crystalline silicon nanowires.

[0018] S1-4. The source and drain electrode patterns are transferred to the SiO2 / n type heavily doped silicon substrate using photolithography. The oxide layer on the surface of the crystalline silicon nanowire is then removed by buffer oxide etching solution. Platinum and aluminum are then deposited sequentially on the surface of the SiO2 / n type heavily doped silicon substrate. The source and drain electrodes are prepared by a lift-off process. Finally, the back gate electrode is led out using conductive silver paste to obtain the silicon nanowire field-effect transistor sensor.

[0019] Preferably, in steps S1-3, the annealing treatment method is as follows: using a plasma-enhanced chemical vapor deposition device, H2 plasma annealing treatment is performed at 250~270℃ to reduce the indium oxide strips and condense them into indium catalytic droplets.

[0020] The amorphous silicon layer is prepared at a temperature of 100~120℃.

[0021] Preferably, the step of activating the indium droplet absorption of the pre-coated amorphous silicon layer is as follows: raising the temperature to 340~360℃ and maintaining it for 1~2 hours under a vacuum or hydrogen atmosphere;

[0022] The etching step is as follows: the residual amorphous silicon layer is removed by low-temperature H2 plasma.

[0023] Preferably, in step S2, the substance containing Aβ 1-42 Aβ in phosphate buffer solution of nucleic acid aptamers 1-42 The concentration of the nucleic acid aptamer was 100 nM.

[0024] Preferably, in step S3, the surface functionalization treatment is performed using ozone treatment or O2 plasma treatment, and the surface functionalization treatment time is 90~110s.

[0025] Preferably, the ozone treatment time is 2 minutes;

[0026] The parameters for the O2 plasma treatment are as follows: the substrate temperature is room temperature, the radio frequency power is 20~100W, the reaction-coupled plasma power is 200~500W, the chamber pressure is 0.5~3Pa, the O2 flow rate is 20~200sccm, and the treatment time is 1~20min.

[0027] Preferably, in step S4, the volume fraction of 3-aminopropyltriethoxysilane in the anhydrous ethanol solution containing 3-aminopropyltriethoxysilane is 2-4%.

[0028] The condensation reaction is carried out at a temperature of 20-30°C for 30-60 minutes.

[0029] The heating temperature is 110~130℃, and the time is 10~20min.

[0030] According to a second aspect of the present invention, a silicon nanowire field-effect transistor biosensor obtained according to the above-described preparation method is provided.

[0031] According to a third aspect of the present invention, an application of a silicon nanowire field-effect transistor biosensor in the detection of amyloid protein, a biomarker of Alzheimer's disease, is provided.

[0032] This invention provides a silicon nanowire field-effect transistor biosensor, its fabrication method, and its application. It offers the following advantages:

[0033] (1) The present solution provides a silicon nanowire field-effect transistor biosensor, wherein Aβ is modified on the surface of silicon nanowires. 1-42 Nucleic acid aptamers can target Aβ 1-42 This characteristic biomarker enables rapid, accurate, and highly sensitive detection.

[0034] (2) The method provided in this scheme is to prepare a silicon nanowire field-effect transistor biosensor. The nanowire structure in the plane is prepared by plasma-enhanced chemical vapor deposition. It has excellent performance and high specific surface area. Furthermore, nucleic acid aptamer is modified on its surface, thereby making the detection of biomarkers more sensitive. Attached Figure Description

[0035] Figure 1 This is a schematic diagram illustrating the fabrication process of the silicon nanowire field-effect transistor sensor of the present invention;

[0036] Figure 2 This is a schematic diagram illustrating the process of immobilizing nucleic acid aptamers onto the surface of a silicon nanowire field-effect transistor sensor according to the present invention.

[0037] Figure 3 The XPS full spectrum and N 1s high-resolution spectrum of the silicon nanowires of the present invention at different processing steps are shown.

[0038] Figure 4 The water contact angle of the silicon nanowires of this invention after APTES modification under different treatments varies.

[0039] Figure 5 The images show the surface morphology of the silicon nanowire field-effect transistor sensor of the present invention. (a) is an optical microscope image, and (b) is a scanning electron microscope image.

[0040] Figure 6 The output characteristic curves of the silicon nanowire field-effect transistor sensor before and after immobilization of nucleic acid aptamers according to the present invention are shown.

[0041] Figure 7 The transfer characteristic curves of the silicon nanowire field-effect transistor sensor with immobilized nucleic acid aptamers according to the present invention are shown. Detailed Implementation

[0042] To better illustrate the content of this invention, the following description is provided in conjunction with specific embodiments.

[0043] Example 1

[0044] The fabrication process of a silicon nanowire field-effect transistor biosensor is as follows:

[0045] Step 1: Fabrication of silicon nanowire field-effect transistor sensors, such as... Figure 1 As shown:

[0046] (a) A rectangular photoresist pattern is defined on the SiO2 surface of a SiO2 / n type heavily doped silicon substrate using photolithography;

[0047] (b) Using an inductively coupled plasma etching apparatus, C4F8 and O2 plasmas are used alternately to etch the SiO2 layer multiple times to form a multi-stage guided step structure;

[0048] (c) Then, place the sample in acetone, ethanol, and deionized water in sequence for ultrasonic treatment to remove the surface photoresist;

[0049] (d) Deposit a strip of indium metal of a certain width on the surface of a multi-level guide step using electron beam evaporation;

[0050] (e) The indium oxide strips are reduced and condensed into uniform diameter indium catalytic droplets by H2 plasma annealing at 250°C using plasma-enhanced chemical vapor deposition equipment.

[0051] (f) At a reaction temperature of 100°C, SiH4 gas is introduced to deposit an amorphous silicon thin film on the surface of the guide step;

[0052] (g) Then the temperature is raised to 350°C and maintained in a vacuum or hydrogen atmosphere for 1 hour to activate the indium droplet, causing it to move along the sidewall, absorb and coat the amorphous silicon film, and grow uniform crystalline silicon nanowires along the stepped sidewall. After the silicon nanowire growth is completed, the remaining amorphous silicon layer is selectively removed by a low-temperature H2 plasma etching process to obtain high-quality and uniform crystalline silicon nanowires.

[0053] (h) The source and drain electrode patterns are transferred to a SiO2 / n type heavily doped silicon substrate using photolithography. Then, the oxide on the surface of the crystalline silicon nanowires is removed by buffer oxide etching solution. Platinum and aluminum are then deposited sequentially on the surface of the SiO2 / n type heavily doped silicon substrate. The source and drain electrodes are prepared by a lift-off process. Finally, the back gate electrode is led out using conductive silver paste to obtain a silicon nanowire field-effect transistor sensor.

[0054] Step 2: Immobilization of nucleic acid aptamers on the silicon nanowire field-effect transistor sensor, such as... Figure 2 As shown:

[0055] (a) The silicon nanowires of the silicon nanowire field-effect transistor sensor were subjected to ozone treatment for 100s, of which the ozone treatment time was 2min.

[0056] (b) The silicon nanowires of the silicon nanowire field-effect transistor sensor were placed in an anhydrous ethanol solution containing 2% by volume of 3-aminopropyltriethoxysilane and allowed to stand at room temperature for 30 min to promote the condensation reaction to form amide bonds. Then, the silicon nanowire field-effect transistor sensor was rinsed with anhydrous ethanol solution to remove uncoupled APTES and heated at 120 °C for 10 min to enhance the coupling strength.

[0057] (c) Adding 100 nM Aβ solution to the silicon nanowires of a silicon nanowire field-effect transistor sensor at room temperature 1-42 Nucleic acid aptamer PBS solution, after standing for 2 hours, is stored at 4°C for later use. Aβ is included. 1-42 The base sequence of the nucleic acid aptamer is: 5'-NH2-(CH2)4-UAGCGUAUGCCACUCUCCUGGGACCCCCCGCCGGAUGGCCA-CAUCC-3'.

[0058] The surface morphology image of the silicon nanowire field-effect transistor biosensor prepared in this embodiment is shown below. Figure 5 As shown.

[0059] Example 2

[0060] The preparation method of this embodiment is the same as that of the previous embodiment. The difference is that in the process of fixing the nucleic acid aptamer on the silicon nanowire field-effect transistor sensor, step (a) uses an inductively coupled plasma etching device to perform surface treatment on the silicon nanowires with O2 plasma for 100s.

[0061] Performance testing

[0062] (1) X-ray electron spectroscopy was used to characterize the silicon nanowires before and after APTES modification and nucleic acid aptamer immobilization to verify whether the nucleic acid aptamers were successfully immobilized on the surface of the silicon nanowires, as well as the changes in elemental composition before and after immobilization. The results were also compared with untreated silicon nanowires. Figure 3 As shown.

[0063] in, Figure 3 Figure (a) shows the XPS full spectrum of Example 1 after ozone treatment. The red curve represents the full spectrum of silicon nanowires after any treatment, mainly containing Si 2p and C 1s peaks; the blue curve is the full spectrum of silicon nanowires modified with APTES after ozone treatment, showing N 1s and O 1s peaks, indicating successful amination modification on the surface of the silicon nanowires; the green curve is the full spectrum after further immobilization of nucleic acid aptamers.

[0064] Figure 3 Figure (b) shows the XPS full spectrum of silicon nanowires treated with O2 plasma in Example 2. The red curve represents the full spectrum of untreated silicon nanowires, mainly containing Si 2p and C 1s peaks; the blue curve is the full spectrum of silicon nanowires modified with APTES after O2 plasma treatment, showing N 1s and O 1s peaks, indicating successful amination modification; the green curve shows the full spectrum after further immobilization of nucleic acid aptamers; from Figure 3 A comparison of Figures (a) and (b) shows that ozone treatment and O2 plasma treatment can be substituted for each other, and both methods can effectively achieve APTES modification and nucleic acid aptamer immobilization.

[0065] Figure 3 Figure (c) shows the high-resolution N 1s spectrum of the untreated silicon nanowire. The N 1s signal is close to the background noise, indicating that no significant nitrogen element was detected on the surface of the original silicon nanowire. Figure 3 Figure (d) shows the high-resolution N 1s spectrum of APTES-modified silicon nanowires after ozone treatment. After APTES modification, the N 1s peak is significantly enhanced, and multiple chemical states of N 1s peaks appear, such as C–NH2 (400.51 eV), C–NH–C (401.59 eV), and NSi. x O (399.41 eV) proves that the APTES modification was successful; Figure 3Figure e shows the N 1s high-resolution spectrum of silicon nanowires after ozone treatment to immobilize nucleic acid aptamers, in which the C–NH2 peak is enhanced (400.86 eV), indicating that nitrogen element was successfully introduced into the aptamer molecule.

[0066] The combined XPS full-spectrum and N 1s high-resolution spectra show that APTES can be successfully modified on the surface of silicon nanowires after ozone or O2 plasma treatment, further immobilizing nucleic acid aptamers. The N 1s peak shows significant changes during the modification process, reflecting the chemical characteristics of APTES modification and nucleic acid aptamer immobilization. These signal changes reflect the chemical characteristics of the modification process, verifying the effectiveness of the functionalization treatment of the silicon nanowire surface and aptamer immobilization, providing a solid foundation for the development of biosensors based on silicon nanowire field-effect transistors. This result demonstrates that this technology can be used to construct highly sensitive biosensors for detecting Alzheimer's disease-related biomarkers.

[0067] (2) Figure 4 The water contact angle of silicon nanowires modified with APTES after different treatments varies, specifically... Figure 4 Figure (a) shows the change in water contact angle after ozone treatment and APTES modification in Example 1. After three measurements, the initial water contact angles of the silicon nanowires were 29.9°, 33.9° and 35.0°, respectively. After ozone treatment, the water contact angles decreased to 21.6°, 26.7° and 26.6°, indicating that ozone treatment improved the hydrophilicity of the surface. After APTES modification, the water contact angles increased to 65.7°, 50.6° and 54.1°. Figure 4 Figure (b) shows the change in water contact angle after O2 plasma treatment and APTES modification in Example 2. After three measurements, the water contact angle further decreased to 26.7°, 25°, and 33.7° after O2 plasma treatment, while it increased to 25.3°, 31.9°, and 30° after APTES modification. APTES forms siloxane bonds by condensing its ethoxy groups with the hydroxyl groups on the silicon surface, introducing amino functional groups into the silicon nanowire surface. The introduction of these amino functional groups changes the chemical properties of the surface, thus transforming the silicon nanowire surface from hydrophilic to hydrophobic. After APTES modification, the water contact angle of the ozone-treated sample increased significantly, indicating successful modification and making the surface more hydrophobic. Furthermore, a comparison between Example 1 and Example 2 shows that the APTES modification effect of the sample after O2 plasma treatment is slightly worse than that after ozone treatment.

[0068] (3) Aβ of the silicon nanowire field-effect transistor sensor prepared in Example 1 1-42 Nucleic acid aptamer specificity measurement, measurement from 10 -7 M to 10 -15Aβ at different concentrations of M 1-42 The solution is dropped onto the sensor surface, therefore I ds -V gs change.

[0069] First, perform Aβ 1-42 Solution preparation: Add Aβ 1-42 After the lyophilized powder was dissolved in hexafluoroisopropanol (HFIP) until the powder was completely dissolved to form a clear and transparent solution, it was gently vortexed and incubated at room temperature for 30 min to obtain a homogeneous, aggregate-free Aβ. 1-42 The monomer solution was mixed with 60 μL of 20 μM sodium hydroxide solution, and HFIP was evaporated under nitrogen to obtain Aβ with a concentration of 1 mM. 1-42 Monomer solution, successively diluted to 10 -7 M to 10 -15 Different concentrations of M were used and stored at -20°C.

[0070] Figure 6 Figures (a) and (b) show the output characteristic curves of the silicon nanowire field-effect transistor sensor before and after immobilization of the nucleic acid aptamer, respectively, and the drain current I. ds With the drain voltage V ds The relationship between the changes in gate voltage V gs The test was conducted below, and as shown in the figure, with the gate voltage V... gs The output current increases significantly from 0 V to -6 V, indicating that a larger negative gate bias can enhance the carrier concentration in the channel, thereby improving conductivity. Compared to... Figure 6 (a), Figure 6 (b) The output current after immobilization of the nucleic acid aptamer generally shifts to the left, and the drain current I ds Significantly reduced, at the same drain voltage V ds and gate voltage V gs It exhibits a lower current value. Aβ 1-42 Nucleic acid aptamers are negatively charged. When immobilized on the surface of silicon nanowires, they alter the surface potential and carrier distribution of the device channels through charge effects. In an n-type heavily doped silicon substrate and SiO2 insulating layer structure, the immobilized negatively charged nucleic acid aptamers reduce the electron density at the surface of the silicon nanowire channels, leading to a decrease in channel conductivity and consequently, an increase in the drain current Id. ds The decrease in output characteristic curve further demonstrates the successful immobilization of the nucleic acid aptamer on the device surface. Furthermore, Figure 6 (b) with the gate voltage V gs The drain current I changes from 0 V to -6 V. dsThe magnitude of the change decreased. This indicates that the negative charge of the nucleic acid aptamer has a certain degree of shielding effect on the conductance, thus weakening the gate's ability to regulate the device. The decrease in device conductance after nucleic acid aptamer immobilization is the basis for its biosensing function. By changing the surface negative charge density after the aptamer binds to the target molecule, the device's conductance characteristics will change further. This change in output signal can be used to detect the presence and concentration of the target molecule. This phenomenon demonstrates the sensitivity of silicon nanowire field-effect transistors to surface modification, and also indicates that nucleic acid aptamer immobilization is a key step in the biochemical function of the device.

[0071] Figure 6 Figure (c) shows the effects of adding different concentrations of Aβ-containing reagents after immobilizing nucleic acid aptamers at a constant drain voltage. 1-42 The transfer characteristic curve after solution treatment. Based on... Figure 6 (c) It can be seen that as Aβ 1-42 As the concentration increases, the transfer curve gradually shifts, indicating that the threshold voltage V of the device... th With Aβ 1-42 The change in concentration is due to the alteration of surface charge distribution caused by the specific binding of the target molecule to the aptamer, which in turn modulates the device's conductivity and causes a change in the output signal.

[0072] Figure 6 Figure (d) shows the addition of different concentrations of Aβ-containing reagents after immobilization of nucleic acid aptamers. 1-42 The concentration dependence of the threshold voltage Vth after buffering was observed. A clear linear relationship was observed between the threshold voltage and concentration (at 10...). -14 M to 10 -11 (within the range of M) further demonstrates that the nucleic acid aptamer-modified biosensor can detect Aβ. 1-42 The concentration can be sensitively detected, and Aβ at the 10 fM level can be detected. 1-42 .

[0073] Figure 7 The transfer characteristic curves of silicon nanowire field-effect transistors before immobilization of nucleic acid aptamers are shown. The red curve in the figure (V...) gs =-0.1 V) and the green curve (V gs Both (e.g., -0.5 V) exhibit typical p-type field-effect transistor characteristics. Drain voltage V ds With gate voltage V gs The gradual increase in voltage as the gate voltage decreases indicates that the negative gate voltage enhances the channel's conduction capability. The device's on / off ratio I... on / I off ≈10 5 This indicates that the device has high sensitivity and good switching performance.

[0074] Aβ levels in cerebrospinal fluid of cognitively normal individuals and Alzheimer's patients 1-42 There were significant differences in concentration, Aβ 1-42 >325 pg / mL (approximately 10 -13 Aβ (M) is used as a standard for "amyloid-negative," while concentrations below this value may reflect abnormal accumulation of amyloid protein. Aβ in the plasma of Alzheimer's disease patients... 1-42 Concentrations are typically between 10 pg / mL and 100 pg / mL, approximately 2 × 10⁻⁶. -15 M~2×10 -14 M, the silicon nanowire field-effect transistor biosensor prepared in this invention for Aβ 1-42 The minimum concentration for concentration detection is 10. -14 M can provide accurate test results for the early detection and intervention of Alzheimer's disease.

[0075] 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 fabricating a silicon nanowire field-effect transistor biosensor, characterized in that: Includes the following steps: S1. Fabrication of silicon nanowire field-effect transistor sensors; S2, Configuration containing Aβ 1-42 Phosphate-buffered saline solution of nucleic acid aptamers, wherein the Aβ 1-42 The base sequence of the nucleic acid aptamer is: 5'-NH2-(CH2)4-UAGCGUAUGCCACUCUCCUGGGACCCCCCGCCGGAUGGCCA-CAUCC-3'; S3. Surface functionalization treatment of silicon nanowires in silicon nanowire field-effect transistor sensors. S4. The silicon nanowires of the silicon nanowire field-effect transistor sensor are placed in an anhydrous ethanol solution containing 3-aminopropyltriethoxysilane for a condensation reaction. After the condensation reaction is complete, the mixture is washed with anhydrous ethanol, heated, and finally the solution containing Aβ is added dropwise. 1-42 The PBS solution of the nucleic acid aptamer was allowed to stand for 2-4 hours and then stored at 4°C for later use.

2. The method for fabricating a silicon nanowire field-effect transistor biosensor according to claim 1, characterized in that: In step S1, the silicon nanowire field-effect transistor sensor is fabricated as follows: S1-1. Define a rectangular photoresist pattern on the surface of the SiO2 layer of a SiO2 / n-type heavily doped silicon substrate using photolithography. S1-2. Using inductively coupled plasma etching technology, C4F8 and O2 plasmas are used alternately to etch the SiO2 layer to obtain a multi-level guided step structure. Then, the layer is ultrasonically treated in acetone, ethanol and deionized water in sequence to remove the photoresist on the surface. S1-3. Electron beam evaporation is used to deposit indium strips on the surface of the multi-stage guided step structure. Then, annealing is performed to reduce the indium oxide strips and condense them into catalytic indium droplets. Then, SiH4 gas is introduced to deposit an amorphous silicon film on the surface of the multi-stage guided step structure. Finally, the indium droplets are activated to absorb the pre-coated amorphous silicon film, and etched to obtain crystalline silicon nanowires. S1-4. The source and drain electrode patterns are transferred to the SiO2 / n type heavily doped silicon substrate using photolithography. The oxide layer on the surface of the crystalline silicon nanowire is then removed by buffer oxide etching solution. Platinum and aluminum are then deposited sequentially on the surface of the SiO2 / n type heavily doped silicon substrate. The source and drain electrodes are prepared by a lift-off process. Finally, the back gate electrode is led out using conductive silver paste to obtain the silicon nanowire field-effect transistor sensor.

3. The method for fabricating a silicon nanowire field-effect transistor biosensor according to claim 2, characterized in that: In steps S1-3, the annealing process is as follows: using a plasma-enhanced chemical vapor deposition device, H2 plasma annealing is performed at 250~270℃ to reduce the indium oxide strips and condense them into indium catalytic droplets. The amorphous silicon thin film is prepared at a temperature of 100~120℃.

4. The method for fabricating a silicon nanowire field-effect transistor biosensor according to claim 2, characterized in that: In steps S1-3, the step of activating indium droplets to absorb the pre-coated amorphous silicon film is as follows: under a vacuum or hydrogen atmosphere, the temperature is raised to 340~360℃ and maintained for 1~2 hours; The etching step is as follows: removing the residual amorphous silicon film by low-temperature H2 plasma.

5. The method for fabricating a silicon nanowire field-effect transistor biosensor according to claim 1, characterized in that: In step S2, the substance containing Aβ 1-42 Aβ in phosphate buffer solution of nucleic acid aptamers 1-42 The concentration of the nucleic acid aptamer was 100 nM.

6. The method for fabricating a silicon nanowire field-effect transistor biosensor according to claim 1, characterized in that: In step S3, the surface functionalization treatment is performed using ozone treatment or O2 plasma treatment, and the surface functionalization treatment time is 90~110s.

7. The method for fabricating a silicon nanowire field-effect transistor biosensor according to claim 6, characterized in that: The parameters for the O2 plasma treatment are as follows: the substrate temperature is room temperature, the radio frequency power is 20~100W, the reaction-coupled plasma power is 200~500W, the chamber pressure is 0.5~3Pa, the O2 flow rate is 20~200sccm, and the treatment time is 1~20min.

8. The method for fabricating a silicon nanowire field-effect transistor biosensor according to claim 1, characterized in that: In step S4, the volume fraction of 3-aminopropyltriethoxysilane in the anhydrous ethanol solution containing 3-aminopropyltriethoxysilane is 2-4%. The condensation reaction is carried out at a temperature of 20-30°C for 30-60 minutes. The heating temperature is 110~130℃, and the time is 10~20min.

9. A silicon nanowire field-effect transistor biosensor obtained by the preparation method according to any one of claims 1 to 8.

10. The application of the silicon nanowire field-effect transistor biosensor of claim 9 in the detection of amyloid protein, a biomarker of Alzheimer's disease.

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