Biosensing element, biosensor and biological detection chip

Abstract

A biosensing element. The biosensing element comprises: a substrate, and a thin film transistor and a reaction chamber which are located on one side of the substrate. The thin film transistor comprises: a gate, a gate insulating layer, an active layer, a source and a drain which are stacked. The thin film transistor is located in the reaction chamber, and antibodies are provided in the reaction chamber. The thin film transistor further comprises a protective layer including at least one of a first protective layer and a second protective layer, wherein the first protective layer is located between the gate insulating layer and the active layer, the second protective layer comprises a first portion that is located on the side of the part of the active layer exposed by the source and the drain away from the substrate, and a water contact angle of a material of the protective layer is greater than that of a material of the gate insulating layer.

Description

Biosensing element, biosensor and bio-detection chip

[0001] This application claims priority to Chinese Patent Application No. 202510080758.9, filed on January 17, 2025, the entire contents of which are incorporated herein by reference. TECHNICAL FIELD

[0002] The present disclosure relates to the field of chip technology, and in particular, to a biosensing element, a biosensor and a bio-detection chip. BACKGROUND

[0003] Thin Film Transistor (TFT) type biosensor technology, as a fast, accurate and label-free detection technology, has been used in medical and environmental analysis. In the field of clinical diagnosis, it is predicted that there will be an increasing demand for rapid bedside detection analysis near the testee in different fields.

[0004] The electrical detection method can realize label-free detection, which utilizes the electrical signal changes of the surface potential, electric potential or electric conductance of the biomolecular carrier material caused by DNA hybridization reaction or antigen-antibody biological recognition reaction to realize detection. The detection process is simple and fast, with high detection sensitivity, without the need for complex detection equipment, and can truly achieve the purpose of low cost, miniaturization and portability. SUMMARY

[0005] In one aspect, a biosensing element is provided, comprising: a substrate, a thin film transistor and a reaction chamber located on one side of the substrate, the thin film transistor comprising: a gate electrode, a gate insulating layer, an active layer, a source electrode and a drain electrode which are stacked, the thin film transistor being located in the reaction chamber, and an antibody being arranged in the reaction chamber; the thin film transistor further comprises: a protective layer, the protective layer comprising: at least one of a first protective layer and a second protective layer; wherein the first protective layer is located between the gate insulating layer and the active layer; the second protective layer comprises: a first part, the first part being located on the side of the part of the active layer exposed by the source electrode and the drain electrode away from the substrate; wherein the water contact angle of the material of the protective layer is greater than the water contact angle of the material of the gate insulating layer.

[0006] In some embodiments, the material of the protective layer comprises any one of: an organic semiconductor material, an inorganic semiconductor material and a hydrophobic material.

[0007] In some embodiments, the material of the protective layer comprises at least one of the following groups. -F and -CN.

[0008] wherein R1 is selected from n1 is selected from 1, 2, or 3.

[0009] In some embodiments, the material of the protective layer comprises at least one of the following structural formulas.

[0010] R2 comprises: R3 comprises: R4 comprises: R5 comprises: 2-EtHex, -C 16 H 33 or -(CH2)2CH(C 10 H 21 )2; n2 is selected from a positive integer greater than or equal to 50 and less than or equal to 10,000.

[0011] In some embodiments, the thickness of the protective layer ranges from 5 nm to 100 nm.

[0012] In some embodiments, the material of the protective layer comprises at least one of perfluoroalkyl triethoxysilane, perfluoroalkyl methacrylate, and fluorinated graphene.

[0013] In some embodiments, the thickness of the protective layer ranges from 3 nm to 10 nm.

[0014] In some embodiments, the material of the protective layer is an inorganic semiconductor material, and the density of the material of the protective layer is greater than the density of the material of the gate insulating layer.

[0015] In some embodiments, the material of the protective layer comprises at least one of zinc oxide, zirconium oxide, iridium oxide, titanium dioxide, indium tin oxide, molybdenum disulfide, silicon carbide, and gallium nitride.

[0016] In some embodiments, the thickness of the protective layer ranges from 1 nm to 5 nm.

[0017] In some embodiments, the material of the protective layer comprises at least one of zinc oxide, zirconium oxide, iridium oxide, titanium dioxide, and indium tin oxide; and the antibody is connected to the surface of the first part.

[0018] In some embodiments, the biosensor element further comprises an interlayer medium layer, the interlayer medium layer is located on the side of the first part away from the active layer; the biosensor element further comprises a detection electrode and a sensing electrode located in the reaction cavity, the detection electrode is located on the side of the interlayer medium layer away from the substrate, and the detection electrode is electrically connected to the sensing electrode; wherein the antibody is connected to the surface of the sensing electrode.

[0019] In some embodiments, the material of the protective layer comprises a semiconductor material, and the second protective layer further comprises a second part connected to the first part, wherein the second part is located between the active layer and the source electrode, and between the active layer and the drain electrode.

[0020] In some embodiments, the material of the active layer comprises indium gallium zinc oxide.

[0021] In another aspect, a biosensor is provided, which comprises a plurality of biosensing elements arranged in an array, wherein at least one of the plurality of biosensing elements is the biosensing element according to any one of the above embodiments; the gate of each of the biosensing elements is connected to a gate signal line, respectively; the source of each biosensing element in the same column is connected to the same source connection line; and the drain of each biosensing element in the same row is connected to the same drain connection line.

[0022] In yet another aspect, a biosensor chip is provided, which comprises the biosensor according to any one of the above embodiments, a detector connected to the biosensor, and a controller; wherein the controller is configured to analyze an antigen sample injected into the reaction cavity of each biosensing element of the biosensor according to the electrical signal of the biosensor detected by the detector, and output a detection result.

[0023] In yet another aspect, the biosensor chip according to any one of the above embodiments is applied in the detection of Alzheimer's disease. BRIEF DESCRIPTION OF DRAWINGS

[0024] In order to more clearly illustrate the technical solutions in the present disclosure, the following will briefly introduce the drawings needed to be used in some embodiments of the present disclosure. Obviously, the drawings described in the following description are only the drawings of some embodiments of the present disclosure, and other drawings can also be obtained by those skilled in the art according to these drawings. In addition, the drawings described in the following description can be regarded as schematic diagrams, and are not limited to the actual size, actual process, etc. of the products involved in the embodiments of the present disclosure.

[0025] FIG. 1 is a structural diagram of a biosensor according to some embodiments of the present disclosure;

[0026] FIG. 2 is a sectional view of the biosensor of FIG. 1 along the sectional line AA;

[0027] FIG. 3 is a structural diagram of a biosensing element according to some embodiments of the present disclosure;

[0028] FIG. 4 is another structural diagram of a biosensing element according to some embodiments of the present disclosure;

[0029] FIG. 5 is yet another structural diagram of a biosensing element according to some embodiments of the present disclosure;

[0030] FIG. 6 is a structural diagram of a bio-detection chip according to some embodiments of the present disclosure;

[0031] FIG. 7 is a characteristic transfer curve of an antibody on a bio-sensing element provided by Embodiment 1 of the present disclosure after binding with different concentrations of antigens;

[0032] FIG. 8 is a characteristic transfer curve of a bio-sensing element provided by Embodiments 1-5 and Comparative Example 1 of the present disclosure. DETAILED DESCRIPTION

[0033] The technical solutions in some embodiments of the present disclosure will be described clearly and completely below with reference to the drawings. Obviously, the described embodiments are only some of the embodiments of the present disclosure, but not all the embodiments. Based on the embodiments provided by the present disclosure, all other embodiments obtained by a person of ordinary skill in the art belong to the scope of protection of the present disclosure.

[0034] Unless otherwise required by context, the term "comprise" and other forms of the term "comprise", such as "comprises" and "comprising", are used in the sense of "include", "include but not limited to", or "including, but not limited to", and not in the sense of "consist" or "consisting of". In the description of the specification, the terms "one embodiment", "some embodiments", "exemplary embodiments", "example", "specific example" or "some examples" are intended to mean that the specific feature, structure, material or characteristic related to the embodiment or example is included in at least one embodiment or example of the present disclosure. The illustrative representation of the above terms does not necessarily mean the same embodiment or example. In addition, the specific features, structures, materials or characteristics described can be included in any one or more embodiments or examples in any appropriate manner.

[0035] Hereinafter, the terms "first" and "second" are used only for descriptive purposes, and cannot be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Therefore, the features defined with "first" and "second" can explicitly or implicitly include one or more of the features. In the description of the embodiments of the present disclosure, unless otherwise specified, the meaning of "a plurality of" is two or more.

[0036] In describing some embodiments, the use of "connection" and / or "coupling" and / or terms of similar import will likely be used. The term "connection" is to be construed broadly, for example, a "connection" can be a fixed connection, or a detachable connection, or integral; can be directly connected, or indirectly connected through an intermediate medium. The term "coupling" indicates, for example, that two or more components have direct physical contact or electrical contact. The embodiments disclosed herein are not necessarily limited by the content herein.

[0037] "A, B, and C at least one of" is synonymous with "at least one of A, B, or C," and includes the following combinations of A, B, and C: only A, only B, only C, a combination of A and B, a combination of A and C, a combination of B and C, and a combination of A, B, and C.

[0038] "A and / or B" includes the following three combinations: only A, only B, and a combination of A and B.

[0039] As used herein, "about," "approximately," or "around" includes the recited value and the average value within an acceptable range of deviation from the recited value, as determined by one of ordinary skill in the art taking into account the measurement being discussed and the error associated with measuring a particular quantity (i.e., the limitations of the measurement system).

[0040] As used herein, "parallel," "perpendicular," and "equal" include the recited condition and conditions that approximate the recited condition, the approximation being within an acceptable range of deviation, as determined by one of ordinary skill in the art taking into account the measurement being discussed and the error associated with measuring a particular quantity (i.e., the limitations of the measurement system). For example, "parallel" includes absolute parallel and near parallel, where the acceptable range of deviation for near parallel can be, for example, within 5°; "perpendicular" includes absolute perpendicular and near perpendicular, where the acceptable range of deviation for near perpendicular can also be, for example, within 5°. "Equal" includes absolute equality and near equality, where the acceptable range of deviation for near equality can be, for example, a difference between the two that is less than or equal to 5% of either.

[0041] It should be understood that when a layer or element is referred to as being "on" another layer or substrate, it can be directly on the other layer or substrate, or intervening layers can also be present.

[0042] This document describes exemplary embodiments with reference to cross-sectional views and / or plan views, which are idealized exemplary drawings. In the drawings, the thickness of layers and the area of ​​regions are enlarged for clarity. Therefore, variations in shape relative to the drawings are contemplated due to, for example, manufacturing techniques and / or tolerances. Thus, exemplary embodiments should not be construed as being limited to the shapes of the regions shown herein, but rather include shape deviations due to, for example, manufacturing processes. For example, etched areas shown as rectangular would typically have curved features. Therefore, the regions shown in the drawings are schematic in nature, and their shapes are not intended to show the actual shapes of the areas of the device, nor are they intended to limit the scope of the exemplary embodiments.

[0043] Alzheimer's disease (AD) is a progressive neurodegenerative disease that primarily affects older adults and is the most common cause of dementia. With the increasing aging of the global population, the incidence of AD is rising rapidly, with over 35 million patients worldwide in 2023, and over 10 million patients aged 60 and above in my country.

[0044] Early stages of Alzheimer's disease (AD) often present with no obvious symptoms; however, this stage may be the most effective for treatment. With the approval of anti-AD drugs, early screening and treatment are expected to become effective interventions to inhibit AD progression. Currently, patients in my country are scattered, and the penetration rate of AD testing at the grassroots level is low. Conventional scales and imaging methods are not suitable for detection in primary healthcare settings and are only used for mid-to-late-stage diagnosis, not for early screening.

[0045] Field-effect transistor (FET) biosensors are fast and highly sensitive, and have been widely used in research on early screening of Alzheimer's disease (AD) in recent years. However, the stability and reliability issues of biosensors limit their potential for large-scale application.

[0046] For example, indium gallium zinc oxide thin-film transistors (IGZO-TFTs) are widely used in organic light-emitting diodes (OLEDs) due to their high on / off ratio and high output current.

[0047] However, when a voltage is applied to the IGZO-TFT device, oxygen atoms or ions can migrate in the IGZO thin film, causing changes in the chemical composition and electronic structure of the IGZO thin film. Such changes can affect the conductivity and mobility of the IGZO thin film, causing the IGZO-TFT device to drift in characteristics. Among them, the IGZO-TFT device characteristic drift refers to the change of the electrical characteristics of the TFT when the TFT works for a long time or is affected by a specific environmental condition, causing the threshold voltage of the TFT to drift within a certain range, and the drift of the threshold voltage eventually shows the change of the transfer curve of the TFT characteristics,

[0048] In addition, the IGZO thin film is sensitive to humidity and oxygen in the environment. After applying a voltage, water molecules and oxygen in the environment can react with the IGZO thin film, causing changes in the characteristics of the IGZO thin film, which can also cause the IGZO-TFT device to drift in characteristics.

[0049] Therefore, in order to apply mass-produced IGZO devices to AD early screening detection devices, the problem of transfer curve drift of characteristics needs to be solved.

[0050] Based on this, as shown in FIGS. 1-3, an embodiment of the present disclosure provides a biosensor element 10, FIG. 1 is a structural diagram of a biosensor 100, and FIG. 2 is a cross-sectional view of the biosensor 100 along the cross-sectional line AA of FIG. 1. The biosensor 100 includes the biosensor element 10, and the description of the biosensor 100 is referred to the subsequent content, which is not described here.

[0051] The biosensor element 10 includes a substrate 101, a thin film transistor 102 and a reaction chamber 103 located on one side of the substrate 101. The thin film transistor 102 includes a gate electrode 12, a gate insulating layer 15, an active layer 14, a source electrode 16 and a drain electrode 17 which are stacked, and the thin film transistor 102 is located in the reaction chamber 103. The reaction chamber 103 is provided with an antibody 24.

[0052] For example, the substrate 101 includes a glass substrate, the material of the gate insulating layer 15 includes silicon oxide, and the material of the active layer 14 includes indium gallium zinc oxide.

[0053] In some examples, as shown in FIGS. 2 and 3, the biosensor element 10 further includes an interlayer dielectric layer 21 located on the side of the active layer 14 away from the substrate 101. The biosensor element 10 further includes a detection electrode 22 and a sensing electrode 23 located in the reaction chamber 103. The detection electrode 22 is located on the side of the interlayer dielectric layer 21 away from the substrate 101, and the detection electrode 22 is electrically connected to the sensing electrode 23. Among them, the antibody 24 is connected to the surface of the sensing electrode 23.

[0054] Exemplarily, the material of the interlayer medium layer 21 includes silicon nitride, and the material of the sensing electrode 23 includes gold. For example, in the orthographic projection to the substrate 101, the sensing electrode 23 is in a square shape, and the area of the sensing electrode 23 is 0.64 cm 2 .

[0055] The connection of the antibody 24 to the sensing electrode 23 will be described in the subsequent content, and will not be described here.

[0056] The biosensor element 10 can be used for detecting Alzheimer's disease, wherein the reaction cavity 103 is a containing space for the detection reaction between the sample solution input in the detection process and the antibody pre-set on the sensing electrode 23.

[0057] Exemplarily, the barrier wall 25 is formed by photoresist, and the barrier wall 25 encloses to form a plurality of reaction cavities 103. For example, the height of the barrier wall 25 is 0.5 cm; in the orthographic projection to the substrate 101, the reaction cavity 103 is in a square shape, and the area of the reaction cavity 103 is 1.44 cm 2 .

[0058] The detection principle of the biosensor element 10 is as follows: the detection electrode 22 and the sensing electrode 23 are arranged outside the thin film transistor 102, the antibody 24 is adsorbed on the sensing electrode 23, and reacts with the antigen of the sample solution injected into the reaction cavity 103, for example, biological protein binding. When the protein is combined on the sensing electrode 23, the protein has a double-layer charge in the non-isoelectric point area, the antigen-antibody combination causes the double-layer charge of the solution on the surface of the sensing electrode 23 to change, causing the surface potential of the sensing electrode 23 to change, the electron migration of the detection electrode 22 connected to the sensing electrode 23 changes, further causing the voltage signal of the thin film transistor 102 to change, thereby detecting and analyzing the sample solution.

[0059] In some examples, as shown in FIGS. 2 and 3, in order to improve the stability and accuracy of the biosensor element 10 detection, the thin film transistor 102 further includes: a protective layer 13, the protective layer 13 includes: at least one of a first protective layer 131 and a second protective layer 132; wherein the first protective layer 131 is located between the gate insulating layer 15 and the active layer 14; the second protective layer 132 includes: a first part 1321, the first part 1321 is located on the side of the active layer 14 away from the substrate 101, which is exposed to the source electrode 16 and the drain electrode 17. Wherein the water contact angle of the material of the protective layer 13 is greater than the water contact angle of the material of the gate insulating layer 15.

[0060] The water contact angle is an angle between a tangent line of a solid-liquid interface made at a liquid-solid intersection point and a solid-liquid intersection line on a liquid side. The water contact angle is an important parameter for measuring the wetting performance of the liquid on the material surface. If the angle is less than 90 degrees, the solid surface is hydrophilic, i.e., the liquid is easy to wet the solid, and the smaller the angle, the better the wettability. If the angle is greater than 90 degrees, the solid surface is hydrophobic, i.e., the liquid is not easy to wet the solid and is easy to move on the surface.

[0061] That is, the water contact angle can be used to judge the strength of the hydrophobic performance of the material. The greater the water contact angle of the material, the stronger the hydrophobic performance of the material.

[0062] For example, the hydrogen bond content of the material surface can be tested by XRD (X-ray diffraction) or X-ray photoelectron spectroscopy. The smaller the hydrogen bond content, the stronger the hydrophobic performance of the material.

[0063] The part of the active layer 14 exposed by the source electrode 16 and the drain electrode 17 refers to the part of the active layer 14 not covered by the source electrode 16 and the drain electrode 17 after the source electrode 16 and the drain electrode 17 are formed. It can also be understood as the part of the active layer 14 not covered by the source electrode 16 and the drain electrode 17 in the orthographic projection of the substrate 101.

[0064] For example, the thin film transistor 102 includes the first protective layer 131. In another example, the thin film transistor 102 includes the second protective layer 132.

[0065] For example, as shown in FIG. 3, the thin film transistor 102 includes the first protective layer 131 and the second protective layer 132.

[0066] From the above analysis of the influence of the change of the IGZO film on the performance of the IGZO-TFT device, it can be known that the IGZO film is the active layer 14, and the oxygen atoms or oxygen ions can migrate in the active layer 14, causing the chemical composition and electronic structure of the active layer 14 to change. In addition, the active layer 14 is sensitive to humidity and oxygen in the environment. When a voltage is applied to the gate electrode 12, the moisture and oxygen in the environment can react with the active layer 14, causing the characteristics of the active layer 14 to change, thereby causing the transfer curve of the characteristics of the thin film transistor 102 to drift, and making the stability and accuracy of the biological sensing element 10 poor.

[0067] The embodiments of this disclosure, through the provision of protective layer 13, have a stronger hydrophobicity due to the larger water contact angle of the material of protective layer 13 compared to the material of gate insulating layer 15. The provision of the first part 1321 of the second protective layer 132 can improve the resistance of the active layer 14 to water and oxygen corrosion. The provision of the first protective layer 131 can avoid the problem of oxygen vacancy defects caused by lattice mismatch between the active layer 14 and the gate insulating layer 15, or the first protective layer 131 can fill oxygen vacancy. Therefore, the first protective layer 131 can effectively prevent the problem of charge traps formed on the surface of the gate insulating layer 15 under bias voltage due to charge carrier transitions between the active layer 14 and the gate insulating layer 15, thereby alleviating the problem of characteristic transfer curve drift of the thin-film transistor 102 and improving the stability of the thin-film transistor 102, thus improving the stability and accuracy of the detection performance of the biosensing element 10.

[0068] In some embodiments, as shown in FIG3, the material of the protective layer 13 includes any one of organic semiconductor materials, inorganic semiconductor materials, and hydrophobic materials.

[0069] For example, the material of the protective layer 13 includes at least one of the following groups. -F and -CN.

[0070] Wherein, R1 is selected from n1 is selected from 1, 2, or 3. In the above structural formula, n1 is used... This indicates that the bond is used to connect with other groups.

[0071] The above-mentioned groups are highly electronegative groups. The stronger the electron-acquiring ability of the organic material containing the above-mentioned groups, the deeper its energy level structure. The protective layer 13 formed by the organic material can prevent the active layer 14 from contacting the gate insulating layer 15 to form a charge trap, alleviate the problem of characteristic transfer curve drift of the thin film transistor 102, and improve the stability of the thin film transistor 102, so as to improve the stability and accuracy of the detection performance of the biosensing element 10.

[0072] In some embodiments, as shown in FIG3, the material of the protective layer 13 includes at least one of the following structural formulas.

[0073] R2 includes: R3 includes: R4 includes: R5 includes: 2-EtHex, -C 16 H 33 or -(CH2)2CH(C 10 H 21)2; n2 is selected from positive integers greater than or equal to 50 and less than or equal to 10000. Among them, EtHex is an abbreviation for ethoxyacetylene.

[0074] P(NDI2OD-T2) is poly{[N,N′-bis(2-octyldodecyl)benzo[LMN][3,8]o-diazaphenanthroline-1,3,6,8(2H,7H)-tetraone-4,9-diyl)([2,2′]dithienyl-5,5′-diyl)}, also known as N2200.

[0075] Among them, P(NDI2OD-T2), P(NDI2OD-BiTz), PTzNDI-2FT, PNBT, P(NDI-BBTV-F), BDPPV and F4BDOPV-2T are n-type organic polymers containing highly electronegative groups. They are electron transport materials and belong to organic semiconductor materials.

[0076] Different values ​​of n2 result in n-type organic polymers with different molecular weights. The protective layer 13 formed using the above-mentioned n-type organic polymers is less prone to generating oxygen vacancies, alleviating the problem of characteristic transfer curve drift of thin-film transistor 102, improving the stability of thin-film transistor 102, and thus improving the stability and accuracy of the detection performance of biosensor 10.

[0077] Structural formulas I-1, I-2, I-3, I-4, I-5, I-6, I-7, I-8, I-9, I-10, I-11, I-12, and I-13 are n-type organic small molecule materials containing highly electronegative groups. They are electron transport materials and belong to organic semiconductor materials. The protective layer 13 formed using the above-mentioned n-type organic small molecule materials is less prone to generating oxygen vacancies, thus alleviating the problem of characteristic transfer curve drift in thin-film transistor 102.

[0078] In some embodiments, as shown in FIG3, when the material of the protective layer 13 is an organic semiconductor material, the thickness d1 of the protective layer 13 ranges from 5nm to 100nm.

[0079] For example, the thickness d1 of the protective layer 13 can be 5nm, 10nm, 15nm, 20nm, 25nm, 30nm, 35nm, 40nm, 45nm, 50nm, 55nm, 60nm, 65nm, 70nm, 75nm, 80nm, 85nm, 90nm, 95nm or 100nm, etc., and there is no limitation here.

[0080] For example, the thickness d11 of the first protective layer 131 and the thickness d12 of the second protective layer 132 can be the same or different, and there is no limitation here.

[0081] When the material of the protective layer 13 is an organic semiconductor material, by setting the thickness d1 of the protective layer 13 to be in the range of 5nm to 100nm, it is possible to improve the resistance of the active layer 14 to water and oxygen corrosion and effectively avoid the problem of charge traps formed on the surface of the gate insulating layer 15 when the active layer 14 and the gate insulating layer 15 are subjected to bias voltage. This can alleviate the problem of drift in the characteristic transfer curve of the thin film transistor 102, improve the stability of the thin film transistor 102, and thus improve the stability and accuracy of the detection performance of the biosensing element 10.

[0082] In some embodiments, as shown in FIG3, the material of the protective layer 13 includes at least one of perfluoroalkyltriethoxysilane, perfluoroalkyl methacrylate, and fluorinated graphene.

[0083] Among them, the chemical formula of perfluoroalkyltriethoxysilane is C6F. 15 O3Si, the chemical formula of perfluoroalkyl methacrylate is C4F3HO2. Fluorinated graphene is a two-dimensional planar structure, which is a product of partial or complete fluorination of graphene, in which carbon atoms and fluorine atoms are bonded in the form of covalent bonds.

[0084] Perfluoroalkyltriethoxysilane, perfluoroalkyl methacrylate and fluorinated graphene are hydrophobic semiconductor materials that can be vapor-deposited into films, and a protective layer can be formed through the vapor deposition process 13.

[0085] In some embodiments, as shown in FIG3, when the material of the protective layer 13 includes at least one of perfluoroalkyltriethoxysilane, perfluoroalkyl methacrylate and fluorinated graphene, the thickness d1 of the protective layer 13 ranges from 3 nm to 10 nm.

[0086] For example, the thickness d1 of the protective layer 13 is 3nm, 4nm, 5nm, 6nm, 7nm, 8nm, 9nm or 10nm, etc., and there is no limitation here.

[0087] When the material of the protective layer 13 includes at least one of perfluoroalkyltriethoxysilane, perfluoroalkyl methacrylate and fluorinated graphene, by setting the thickness d1 of the protective layer 13 to be in the range of 3nm to 10nm, it is possible to improve the water and oxygen corrosion resistance of the active layer 14 and effectively avoid the problem of charge traps formed on the surface of the gate insulating layer 15 when the active layer 14 and the gate insulating layer 15 are subjected to bias voltage. This alleviates the problem of characteristic transfer curve drift of the thin film transistor 102, improves the stability of the thin film transistor 102, and thus improves the stability and accuracy of the detection performance of the biosensing element 10.

[0088] In some embodiments, as shown in FIG3, the material of the protective layer 13 is an inorganic semiconductor material, and the density of the material of the protective layer 13 is greater than the density of the material of the gate insulating layer 15.

[0089] In semiconductor materials, packing density refers to the percentage of volume occupied by atoms within a unit cell, that is, the ratio of the volume of atoms contained in the unit cell to the volume of the unit cell. It is also known as packing ratio or maximum space utilization.

[0090] The density of inorganic semiconductor materials is greater than that of the gate insulating layer 15. The protective layer 13 formed by using such inorganic semiconductor materials can effectively prevent water and oxygen from entering the active layer 14, thereby improving the water and oxygen corrosion resistance of the active layer 14. Moreover, no charge traps are generated between the interface between the protective layer 13 and the active layer 14, which alleviates the problem of characteristic transfer curve drift of the thin film transistor 102 and improves the stability of the thin film transistor 102, thereby improving the stability and accuracy of the detection performance of the biosensing element 10.

[0091] In some embodiments, as shown in FIG3, the material of the protective layer 13 includes at least one of zinc oxide, zirconium oxide, iridium oxide, titanium dioxide, indium tin oxide, molybdenum disulfide, silicon carbide, and gallium nitride.

[0092] For example, iridium oxide is iridium trioxide, with the chemical formula Ir₂O₃ and a molecular weight of 432.432.

[0093] Zinc oxide, zirconium oxide, iridium oxide, titanium dioxide, indium tin oxide, molybdenum disulfide, silicon carbide, and gallium nitride are all inorganic semiconductor materials with high density. The protective layer 13 formed by these materials can fill oxygen vacancies, thereby improving the stability of the thin film transistor 102 and thus improving the stability and accuracy of the detection performance of the biosensor 10.

[0094] In some embodiments, as shown in FIG3, when the material of the protective layer 13 is an inorganic semiconductor material, the thickness d1 of the protective layer 13 ranges from 1 nm to 5 nm.

[0095] For example, the thickness d1 of the protective layer 13 is 1nm, 2nm, 3nm, 4nm or 5nm, etc., and there is no limitation here.

[0096] For example, an inorganic semiconductor material is formed into a protective layer 13 by a sputtering process.

[0097] When the material of the protective layer 13 is an inorganic semiconductor material, by setting the thickness d1 of the protective layer 13 to be in the range of 1nm to 5nm, it is possible to improve the water and oxygen corrosion resistance of the active layer 14 and effectively avoid the problem of charge traps formed on the surface of the gate insulating layer 15 when the active layer 14 and the gate insulating layer 15 are subjected to bias voltage. This can alleviate the problem of characteristic transfer curve drift of the thin film transistor 102, improve the stability of the thin film transistor 102, and thus improve the stability and accuracy of the detection performance of the biosensing element 10.

[0098] In some embodiments, as shown in FIG3, the materials of the first protective layer 131 and the second protective layer 132 may be the same or different, and no limitation is set here.

[0099] In some embodiments, as shown in FIG4, when the material of the protective layer 13 includes at least one of zinc oxide, zirconium oxide, iridium oxide, titanium dioxide and indium tin oxide, the antibody 24 is attached to the surface of the first part 1321.

[0100] Because the protective layer 13, formed by zinc oxide, zirconium oxide, iridium oxide, titanium dioxide, and indium tin oxide, has hydroxyl groups on its surface, the presence of these hydroxyl groups allows antibody 24 to be attached to the surface of the first part 1321. A description of antibody 24 attachment to the surface of the first part 1321 will follow later and will not be elaborated here.

[0101] By attaching antibody 24 to the surface of the first part 1321, the formation of detection electrode 22 and sensing electrode 23 is unnecessary, simplifying the fabrication steps of biosensor 10. Furthermore, this biosensor 10 can more directly detect changes in interfacial charge caused by antibody-antigen binding, without requiring a dual-gate structure formed by detection electrode 22 and gate 12 to control conduction detection, thus facilitating more sensitive detection performance of the biosensor 10.

[0102] In some embodiments, as shown in FIG4 and FIG5, the material of the protective layer 13 includes a semiconductor material, and the second protective layer 132 further includes a second part 1322 connected to the first part 1321; the second part 1322 is located between the active layer 14 and the source electrode 16, and between the active layer 14 and the drain electrode 17.

[0103] In other words, the second protective layer 132 covers the surface of the active layer 14 away from the substrate 101 and the side surface of the active layer 14. Thus, after the second protective layer 132 is formed by sputtering, the portions of the second protective layer 132 located between the active layer 14 and the source electrode 16 and between the active layer 14 and the drain electrode 17 do not need to be removed, so as to form the second portion 1322.

[0104] Moreover, when the second protective layer 132 includes the first part 1321 and the second part 1322, the second protective layer 132 has a larger coverage area on the active layer 14, which allows the second protective layer 132 to better protect the active layer 14 from water and oxygen erosion.

[0105] Furthermore, since the protective layer 13 is made of a semiconductor material, the arrangement of the second part 1322 does not affect the electron transport between the active layer 14 and the source 16, or between the active layer 14 and the drain 17. For example, when the protective layer 13 is made of an organic semiconductor material, the polymer material itself has deeper least occupied molecular orbitals, which is beneficial for electron transport from the active layer 14 to the source 16 and the drain 17. When the protective layer 13 is made of an inorganic semiconductor material, the thickness d1 of the protective layer 13 ranges from 1 nm to 5 nm, and this thickness d1 does not affect the electron transport from the active layer 14 to the source 16 and the drain 17.

[0106] As shown in Figures 1 to 3, embodiments of this disclosure also provide a biosensor 100, which includes a plurality of biosensing elements 10 arranged in an array, wherein at least one of the plurality of biosensing elements 10 is a biosensing element 10 as described in any of the above embodiments.

[0107] For example, multiple biosensor elements 10 are arranged in an array along the row direction X and the column direction Y.

[0108] For example, the biosensor 100 has a barrier 25 that encloses to form a plurality of reaction chambers 103. The outer boundary of the barrier 25 has a dimension d2 of approximately 6 cm in the row direction X and a dimension d3 of approximately 5 cm in the column direction Y.

[0109] For example, the biosensor 100 has a dimension d4 of approximately 8 cm in the row direction X and a dimension d5 of approximately 6 cm in the column direction Y.

[0110] Each biosensor 10 has its gate 12 connected to a gate signal line G. The sources 16 of biosensors 10 in the same column are connected to the same source connection line S, and the drains 17 of biosensors 10 in the same row are connected to the same drain connection line D. The gates 12 of the thin-film transistors 102 of each biosensor 10 are controlled by different gate signal lines G, thereby achieving individual control of each biosensor 10.

[0111] The biosensor 100 includes at least one biosensing element 10 as described in any of the above embodiments. Therefore, the biosensor 100 has the same beneficial effects as the biosensing element 10 described above, which will not be repeated here.

[0112] Based on the biosensor 100 described above, as shown in Figures 3 and 6, embodiments of this disclosure also provide a biosensor chip 1000, which includes the biosensor 100, a detector 200 connected to the biosensor 100, and a controller 300. The controller 300 is configured to analyze the antigen samples injected into the reaction chambers 103 of each biosensing element 10 of the biosensor 100 based on the electrical signals of the biosensor 100 detected by the detector 200 and output the detection results.

[0113] In this embodiment, the biodetection chip 1000 controls the biosensor 100 via the controller 300 to detect the sample solution injected into the reaction chamber 103. Based on the electrical signal output by the biosensor 100 detected by the detector 200—that is, the voltage signal formed during the detection process due to the reaction between the adsorbed antibody 24 on the sensing electrode 23 of the biosensor element 10 and the antigen in the sample solution—the controller 300 analyzes the voltage signal to obtain the detection result of the sample solution. Because the biosensor element 10 is provided with a protective layer 13, the detection accuracy and stability of the biodetection chip 1000 are improved, thereby enhancing the detection precision and stability of the biosensor element 10.

[0114] Embodiments of this disclosure also provide an application of the biodetection chip 1000 as described in any of the foregoing embodiments in the detection of Alzheimer's disease.

[0115] Because the biosensor 10 is provided with a protective layer 13, the biosensor 10 has high detection accuracy and detection stability, and the biosensor chip 1000 can be mass-produced for AD early screening detection.

[0116] Based on the content of the biosensing element 10, biosensor 100 and biodetection chip 1000 disclosed herein, the following specific embodiments are provided.

[0117] Example 1

[0118] The structure of the biosensor 10 is shown in Figure 3.

[0119] (1) Preparation of protective layer 13

[0120] The material of protective layer 13 was dissolved in a 5 mg / mL chlorobenzene solution. For example, the material of protective layer 13 was N2200. The structure of N2200 is described above and will not be repeated here. The electron mobility of N2200 is 0.06 cm⁻¹.2 V -1 S -1 .

[0121] In a nitrogen atmosphere, a patterned protective layer 13 was prepared by spin-coating the surface of the sacrificial layer. The coating process was: 1500 rpm (Revolutions Per Minute), spin-coating time was 60 seconds, and film thickness was 10 nm. After removing the sacrificial layer, a patterned protective layer 13 was obtained.

[0122] By spin-coating a second protective layer 132 onto the surface of the active layer 14, water and oxygen in the air can be effectively prevented from penetrating into the active layer 14, thereby improving the stability of the biosensor 10. Furthermore, the presence of the first protective layer 131 prevents the migration of charge carriers from inside the active layer 14 to the interface between the active layer 14 and the first protective layer 131 due to the applied bias from reacting to generate new oxygen vacancies or hydroxyl groups, thus improving the repeatability and stability of the biosensor 10.

[0123] (2) Preparation of sensing electrode 23

[0124] By aligning and bonding a customized hard mask with the biosensor element 10 to be fabricated as the sensing electrode 23, gold material is directly sputtered in the sputtering equipment cavity. After sputtering, the hard mask is peeled off from the biosensor element 10, and the patterned sensing electrode 23 can be obtained directly.

[0125] (3) Antibody modification

[0126] Prior to antibody 24 modification of sensing electrode 23, the process includes: surface modification of sensing electrode 23.

[0127] The steps for surface modification of sensing electrode 23 include: injecting a 10 μg / mL ethanol solution of mercaptohexanoic acid into the surface of sensing electrode 23 and reacting it at room temperature for 4 hours to give sensing electrode 23 a carboxyl functional group, and further activating the carboxyl group by EDC / NHC for use in the next step of antibody modification reaction.

[0128] EDC is short for 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, a crosslinking agent used for the coupling of carboxyl groups with primary amines. EDC is mainly used to activate carboxyl groups, promoting the formation of amides and esters.

[0129] NHC stands for N-heterocyclic carbene. NHC is a class of heterocyclic organic molecules with two-electron coordination ability. Due to its unique coordination properties and stability, it has become an important ligand in the fields of organic synthesis and organometallic chemistry.

[0130] The steps for modifying the antibody 24 of the sensing electrode 23 include: injecting a PBS solution containing 1 mg / mL biotin-labeled P-tau181 antibody into the reaction chamber 103, incubating at room temperature for 3 hours, removing the liquid, washing three times with PBS buffer containing Tris-HCl, aspirating the liquid, and then blocking with 50 μM BSA PBS buffer for 30 minutes. After blocking, removing the liquid, washing three times with PBS buffer containing Tris-HCl, aspirating the liquid, and using it for the next step of testing.

[0131] The pH of the PBS buffer for the P-tau181 antibody is 7.2. PBS buffer is one of the most widely used buffers in biochemical research, and its main components include Na2HPO4, KH2PO4, NaCl, and KCl. It is generally used as a solvent to dissolve and protect reagents. The P-tau181 antibody is a human phosphorylated Tau-P181 protein.

[0132] In the Tris-HCl PBS buffer, the volume ratio of Tris-HCl to PBS is 10%.

[0133] BSA stands for bovine serum albumin, which is a type of albumin found in bovine serum.

[0134] (4) Antigen capture

[0135] PBS buffers containing different gradient concentrations of P-tau181 antigen were introduced into different reaction chambers 103 and incubated at 37°C for 10 minutes. The PBS buffers containing Tris-HCl were aspirated and washed three times, and the liquid was aspirated for the next step of the test.

[0136] The concentration range of P-tau181 antigen is 10 pg / mL to 1 ng / mL, the pH of the PBS buffer is 7.2, and the volume ratio of Tris-HCl to PBS in the Tris-HCl PBS buffer is 10%.

[0137] (5) Detection of biological target molecules

[0138] The electrical performance of the thin-film transistor 102 is tested, and the specific test steps include the following 5.1 to 5.6.

[0139] 5.1 Apply a control signal to the gate 12 of the blank biosensor 10 and measure the initial Ids-Vg (characteristic transfer) curve of the thin film transistor 102 of the blank biosensor 10.

[0140] 5.2. Immerse the biosensing element 10 in the antibody 24 solution so that the antibody 24 is adsorbed on the sensing electrode 23, that is, modify the sensing electrode 23 with antibody 24.

[0141] 5.3 Apply an electrical signal to the drain 17 of the thin film transistor 102 of the biosensing element 10, apply a control signal to the gate 12 of the thin film transistor 102 of each biosensing element 10, and measure the Ids-Vg curve of the biosensing element 10 after antibody 24 modification. The shift in the characteristic transfer curve after antibody 24 modification can be measured.

[0142] 5.4. A sample solution is injected into the reaction chamber 103 of the biosensor element 10. The target antigen in the sample solution specifically binds to the antibody 24, causing a change in the induced charge on the detection electrode 22 of the thin-film transistor 102, i.e., the induced charge Q on the detection electrode 22 changes. G2 =Q SENS The sensing electrode 22 senses the electrical quantity Q. G2 The change in electrical charge Q caused by the reaction between antigen and antibody 24 SENS equal.

[0143] 5.5. The Ids-Vg curve of the thin-film transistor 102 was measured again, and the characteristic transfer curve shifted; V FG =V G1 +Q SENS / C, where V FG V is the equivalent gate voltage of active layer 14. G1 The voltage across gate 12 is given by V, where C is the double-layer capacitance of the water, and V is the equivalent gate voltage. FG Affects IDs.

[0144] 5.6 Compare the initial Ids-Vg curve, the Ids-Vg curve before antibody 24 antigen binding, and the Ids-Vg curve after antibody 24 antigen binding, and obtain the change in value for quantitative analysis of the concentration of P-tau181 antigen.

[0145] Figure 7 shows the characteristic transfer curves of antibody 24 on the biosensor element 10 provided in Embodiment 1 of this disclosure after binding with antigens of different concentrations. The horizontal axis represents the gate voltage Vg, in V; the vertical axis represents the current Ids between the source and drain, in A. Curve 1 represents the Ids-Vg curve of the biosensor element 10 before antibody 24 antigen binding, curve 2 represents the Ids-Vg curve of the biosensor element 10 when the antigen concentration is 100 fg / mL, curve 3 represents the Ids-Vg curve of the biosensor element 10 when the antigen concentration is 1 pg / mL, and curve 4 represents the Ids-Vg curve of the biosensor element 10 when the antigen concentration is 100 pg / mL.

[0146] As shown in Figure 7, compared with the Ids-Vg curve of biosensor element 10 before antigen binding to antibody 24, the characteristic transfer curve of biosensor element 10 remains basically unchanged when the antigen concentration is 100 fg / mL; however, the characteristic transfer curve of biosensor element 10 shifts significantly to the right when the antigen concentrations are 1 pg / mL and 100 pg / mL. Therefore, the drift of the Ids-Vg curve of sample solutions containing different concentrations of antigen is positively correlated with the antigen concentration of the sample solution.

[0147] Example 2

[0148] The structure of the biosensor 10 is shown in Figure 3.

[0149] The protective layer 13 in this embodiment is made of F4BDOPV-2T. The structure of F4BDOPV-2T is described above and will not be repeated here.

[0150] The polymer F4BDOPV-2T was dissolved in a chlorobenzene / NMP (N-Methylpyrrolidone) mixed solvent, wherein the concentration of F4BDOPV-2T was 2 mg / mL and the volume ratio of chlorobenzene to NMP was 9:1. During the preparation of the protective layer 13, the spin-coating speed was 1000 rpm and the spin-coating time was 60 seconds.

[0151] The modification and testing conditions for antibody 24 are as described in Example 1.

[0152] In Example 1, the electron mobility of the material N2200 in the protective layer 13 is 0.06 cm⁻¹. 2 V -1 S -1 In Example 2, the electron mobility of F4BDOPV-2T was 14.9 cm⁻¹. 2 V -1 S -1 The F4BDOPV-2T has a higher electron mobility, which is more conducive to electron transport and can improve the detection sensitivity of the biosensor element 10.

[0153] Example 3

[0154] The structure of the biosensor 10 is shown in Figure 3.

[0155] In this embodiment, the protective layer 13 is made of an n-type organic small molecule material. For example, the protective layer 13 is formed by vapor deposition. The process of forming the protective layer 13 using an n-type organic small molecule material is more suitable for mass production. In addition, compared with n-type organic polymer materials, the n-type organic small molecule material can obtain a protective layer 13 with higher purity through vapor deposition, avoiding charge trapping problems caused by impurities in the material, thereby further improving the working life of the biosensor element 10.

[0156] Example 4

[0157] The structure of the biosensor 10 is shown in Figure 3.

[0158] In this embodiment, the protective layer 13 is made of zinc oxide. For example, a film with a thickness d1 of 5 nm is formed on the side of the active layer 14 away from the substrate 101 by sputtering, and a dense protective layer 13 is formed by further annealing. Compared with organic materials, the inorganic zinc oxide film has lower photoelectric reactivity, which is beneficial to improving the working life of the biosensor element 10.

[0159] Example 5

[0160] The structure of the biosensing element 10 is shown in Figure 4. The protective layer 13 in this embodiment is made of zinc oxide.

[0161] Compared to the biosensor element 10 shown in Figure 3, the fabrication process of the biosensor element 10 in this embodiment is simpler. It avoids the use of expensive precious metal material gold to form the sensing electrode 23, and the antibody 24 directly binds to the surface of the first part 1321 of the protective layer 13. This allows for more direct detection of the interface charge change caused by antibody 24-antigen binding, without the need for dual-gate control of conduction detection, which is beneficial for achieving more sensitive detection performance. At the same time, the setting of the protective layer 13 can effectively prevent the surface of the active layer 14 from directly contacting water, thereby improving the stability of the biosensor element 10.

[0162] For example, zinc oxide has hydroxyl groups on its surface. These hydroxyl groups react with 3-aminopropyltrimethoxysilane to form an amino-modified zinc oxide layer. After further activation with EDC / NHC, antibody 24 can be directly linked to form a biosensor 100. The antibody 24 modification process can be referred to the relevant content in Example 1. The antigen concentration can be directly quantitatively analyzed by detecting the drift of the characteristic transfer curve of the thin-film transistor 102 under different antigen concentration conditions.

[0163] Comparative Example 1

[0164] Compared with Example 5, the thin film transistor 102 in this example does not have a protective layer 13, and the antibody 24 is directly connected to the surface of the active layer 14.

[0165] Figure 8 is a characteristic transfer curve of the biosensor 10 provided in Embodiments 1 to 5 and Comparative Example 1 of this disclosure. The horizontal axis represents the gate voltage Vg, in V; the vertical axis represents the source and drain current Ids, in A.

[0166] Taking the characteristic transfer curve of Example 1 as an example, the closer the inflection point Q of the curve is to 0V, the smaller the threshold voltage offset of the biosensor 10, and the better the characteristics of the biosensor 10.

[0167] As can be seen from Figure 8, the threshold voltage deviation of the biosensor 10 provided in Examples 1 to 4 is relatively small. Compared with the dual-gate biosensor 10 provided in Examples 1 to 4, the threshold voltage deviation of the single-gate biosensor 10 provided in Example 5 is slightly larger. In other words, the characteristics of the dual-gate biosensor 10 provided in Examples 1 to 4 are better than those of the single-gate biosensor 10 provided in Example 5. Compared with the biosensor 10 provided in Examples 1 to 5 with a protective layer 13, the characteristics of the biosensor 10 without a protective layer 13 provided in Comparative Example 1 are relatively poor.

[0168] Therefore, the embodiments of this disclosure improve the resistance of the active layer 14 to water and oxygen corrosion by setting the protective layer 13, and / or effectively avoid the problem of charge traps forming on the surface of the gate insulating layer 15 when the active layer 14 and the gate insulating layer 15 are subjected to bias voltage, thereby alleviating the problem of characteristic transfer curve drift of the thin film transistor 102, improving the stability of the thin film transistor 102, and thus improving the stability and accuracy of the detection performance of the biosensing element 10.

[0169] The above description is merely a specific embodiment of this disclosure, but the scope of protection of this disclosure is not limited thereto. Any variations or substitutions conceived by those skilled in the art within the scope of the technology disclosed in this disclosure should be included within the scope of protection of this disclosure. Therefore, the scope of protection of this disclosure should be determined by the scope of the claims.

Claims

1. A biosensing element, comprising: A substrate, a thin-film transistor located on one side of the substrate, and a reaction chamber. The thin-film transistor includes a gate, a gate insulating layer, an active layer, a source, and a drain, all stacked together. The thin-film transistor is located within the reaction chamber, and an antibody is disposed within the reaction chamber. The thin-film transistor further includes: a protective layer, the protective layer comprising: at least one of a first protective layer and a second protective layer; wherein the first protective layer is located between the gate insulating layer and the active layer; the second protective layer comprises: a first portion located on the side of the active layer exposed by the source and the drain that is away from the substrate; The water contact angle of the material of the protective layer is greater than that of the material of the gate insulating layer.

2. The biosensing element according to claim 1, wherein, The material of the protective layer includes any one of organic semiconductor materials, inorganic semiconductor materials, and hydrophobic materials.

3. The biosensing element according to claim 1 or 2, wherein, The material of the protective layer includes at least one of the following groups; -F and -CN; Wherein, R1 is selected from n1 is selected from 1, 2, or 3.

4. The biosensing element according to claim 3, wherein, The material of the protective layer includes at least one of the following structural formulas; R2 includes: R3 includes: R4 includes: R5 includes: 2-EtHex, -C 16 H 33 or -(CH2)2CH(C 10 H 21 )2; n2 is selected from positive integers greater than or equal to 50 and less than or equal to 10000.

5. The biosensing element according to claim 3 or 4, wherein, The thickness of the protective layer ranges from 5 nm to 100 nm.

6. The biosensing element according to claim 1 or 2, wherein, The protective layer is made of at least one of the following: perfluoroalkyltriethoxysilane, perfluoroalkyl methacrylate, and fluorinated graphene.

7. The biosensing element according to claim 6, wherein, The thickness of the protective layer ranges from 3 nm to 10 nm.

8. The biosensing element according to claim 1 or 2, wherein, The protective layer is made of an inorganic semiconductor material, and the density of the protective layer is greater than that of the gate insulating layer.

9. The biosensing element according to claim 8, wherein, The material of the protective layer includes at least one of zinc oxide, zirconium oxide, iridium oxide, titanium dioxide, indium tin oxide, molybdenum disulfide, silicon carbide, and gallium nitride.

10. The biosensing element according to claim 8 or 9, wherein, The thickness of the protective layer ranges from 1 nm to 5 nm.

11. The biosensing element according to any one of claims 8 to 10, wherein, The material of the protective layer includes at least one of zinc oxide, zirconium oxide, iridium oxide, titanium dioxide, and indium tin oxide; The antibody is attached to the surface of the first part.

12. The biosensing element according to any one of claims 1 to 10, wherein, The biosensing element further includes: an interlayer dielectric layer; the interlayer dielectric layer is located on the side of the first part away from the active layer; The biosensing element further includes: a detection electrode and a sensing electrode located within the reaction chamber, wherein the detection electrode is located on the side of the interlayer dielectric layer away from the substrate, and the detection electrode is electrically connected to the sensing electrode; The antibody is attached to the surface of the sensing electrode.

13. The biosensing element according to any one of claims 1 to 12, wherein, The material of the protective layer includes a semiconductor material, and the second protective layer further includes a second part connected to the first part; the second part is located between the active layer and the source electrode, and between the active layer and the drain electrode.

14. The biosensing element according to any one of claims 1 to 13, wherein, The active layer is made of indium gallium zinc oxide.

15. A biosensor comprising an array of multiple biosensing elements, wherein, At least one of the plurality of biosensing elements is a biosensing element as described in any one of claims 1 to 14; Each of the aforementioned biosensing elements has its gate connected to a gate signal line; The sources of all biosensing elements in the same column are connected to the same source connection line; The drains of all biosensors in the same row are connected to the same drain connection line.

16. A biosensor chip, comprising a biosensor as described in claim 15, a detector connected to the biosensor, and a controller; in, The controller is configured to analyze antigen samples injected into the reaction chambers of each biosensing element of the biosensor based on the electrical signals of the biosensor detected by the detector and output the detection results.

17. The application of a biodetection chip as described in claim 16 in the detection of Alzheimer's disease.

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