A T-gate FET biosensor based on atomic layer deposition semiconductor channel

Abstract

The present invention proposes a T-gate FET biosensor based on an atomic layer deposition semiconductor channel, comprising a substrate, a plurality of T-shaped metal layers are arranged at intervals on the surface of the substrate, a high-k dielectric layer is coated on the substrate and the plurality of T-shaped metal layers, an oxide semiconductor channel layer is coated on the high-k dielectric layer, source-drain metal electrode structures that can be used as source electrodes or drain electrodes are arranged at both ends of the channel layer, and insulating layers are arranged on the source electrode and the drain electrode; the channel layer comprises an oxide semiconductor channel groove in a T-shaped structure, and the surface of the channel layer is modified with a biological probe for specifically capturing target biological molecules; the biological probe is confined within the Debye length of the inner wall of the T-shaped structure groove to overcome the influence of Debye shielding in the detection process; the present invention can overcome the influence of Debye shielding and can detect disease markers with lower concentrations in high ionic strength solutions.

Description

Technical Field

[0001] The invention relates to the technical field of microelectronic devices and sensors, in particular to a T-gate FET biosensor based on an atomic layer deposition semiconductor channel. Background Art

[0002] Field-effect transistor (FET) biosensor FET biosensor is an important research direction of biosensors. Compared with electrochemical biosensors and optical biosensors, it has the advantages of no labeling, high sensitivity, easy integration, easy portability, and only requires a trace amount of biological samples. With the development of low-dimensional nano-semiconductor materials such as one-dimensional and two-dimensional, the performance of field-effect transistor biosensors has been further improved. However, low-dimensional nano-semiconductors have the problem of difficult material preparation and device manufacturing processes, which greatly limits the practical application of field-effect transistor biosensors. Recent studies have shown that oxide semiconductors have high carrier concentrations and mobility, and when their film thickness is greatly reduced, the carrier transport performance is not affected. In addition, the material preparation process of oxide semiconductors is compatible with the existing mainstream thin film growth process, and the device preparation process is also compatible with the CMOS process. Therefore, compared with low-dimensional nano-semiconductor materials, oxide semiconductors will be the most potential semiconductor channel material for large-scale mass production of FET biosensors.

[0003] Although FET biosensors are one of the most promising biodetection technologies, due to the existence of Debye shielding, when detecting biological samples with high ionic strength such as blood, serum, urine, and sweat, the sensitivity of FET biosensors will be greatly reduced or the target molecules will not be detected at all. The current methods to overcome Debye shielding are: (1) Dilution method. Dilute biological samples with high ionic strength with low ionic strength buffer solutions or deionized water. This method is simple and convenient, but excessive dilution will cause serious salt dissolution effect on proteins, which will reduce the specific binding effect and affect the detection results. (2) Desalting method. Purify target molecules from biological samples with high ionic strength and remove irrelevant biological molecules and ions. This method is complex and time-consuming and cannot meet the requirements of instant detection. (3) Modify the sensing surface with polyethylene glycol (PEG) permeable polymer layer. PEG is widely used in biosensor antifouling to increase specificity. It is also used to modify the sensing surface of FET biosensors to overcome Debye shielding to a certain extent. However, PEG is easily oxidized, and the PEG permeable polymer layer cannot penetrate all biological molecules, which may block the target molecules. (4) Optimize the device structure. For example, a flat graphene channel can be deformed into a wrinkled graphene, thereby forming an "electric hot spot" in the concave part, extending the Debye length. However, the preparation process of wrinkled graphene is more difficult than that of flat graphene. In addition to the four main methods listed above, there are also cutting antibody method, destroying double electric layer method, etc. Summary of the invention

[0004] The present invention provides a T-gate FET biosensor based on an atomic layer deposition semiconductor channel, which can overcome the influence of Debye screening and detect disease markers with lower concentrations in a high ionic strength solution.

[0005] The present invention adopts the following technical solutions.

[0006] A T-gate FET biosensor based on an atomic layer deposition semiconductor channel, the sensor comprising a substrate, a plurality of T-shaped metal layers are arranged on the surface of the substrate, a high-k dielectric layer is coated on the substrate and the plurality of T-shaped metal layers, an oxide semiconductor channel layer is coated on the high-k dielectric layer, source-drain metal electrode structures that can be used as source electrodes or drain electrodes are arranged at both ends of the channel layer, and an insulating layer is arranged on the source electrode and the drain electrode;

[0007] The oxide semiconductor channel layer includes a T-shaped structure groove, and its surface is modified with a biological probe for specifically capturing target biological molecules;

[0008] The biological probe is confined within the Debye length of the inner wall of the T-channel to overcome the influence of Debye shielding during the detection process.

[0009] The substrate comprises a silicon wafer. When preparing a T-shaped metal layer spaced apart on the surface of the substrate, a double-layer photoresist structure with a plurality of T-shaped grooves spaced apart on the surface of the substrate silicon wafer is first prepared. The method comprises:

[0010] Method A: sequentially performing spin coating of a double-layer photoresist, baking, ultraviolet exposure, development, fixing, and oxygen plasma residual resist removal processes on a substrate;

[0011] Method B, sequentially performing spin coating of a double-layer photoresist, baking, electron beam exposure, and oxygen plasma residual resist removal processes on a substrate;

[0012] Method C, sequentially performing spin coating of a double-layer photoresist, baking, nano-imprinting, developing, fixing, and oxygen plasma residual resist removal processes on a substrate.

[0013] The double-layer photoresist is composed of two types of photoresists with different sensitivities to ultraviolet light and electron dose. The photoresist in contact with the silicon wafer is the bottom layer photoresist, and the sensitivity of the bottom layer photoresist to ultraviolet light or electron dose is lower than that of the upper layer photoresist. The size of the T-shaped structure is controlled by changing the type, thickness, and exposure conditions of the double-layer photoresist, thereby regulating the performance of the T field effect transistor biosensor.

[0014] The material used for the T-shaped metal layer is one or more of Cr, Ti, Al, Ni, Au, and Pt.

[0015] The high-k dielectric layer is Al2O3, HfO2, ZrO2, La2O3, HfAlOx, HfSiO x 、HfLaO x 、HfZrO x One or more high-k dielectrics such as HfSiON are prepared by atomic layer deposition with a thickness of 5-20 nm.

[0016] The oxide semiconductor channel layer is prepared by atomic layer deposition, and the oxide semiconductor channel layer adopts one or more oxide semiconductor materials such as zinc oxide ZnO, indium oxide In2O3, tin oxide SnO2, gallium oxide Ga2O3, titanium oxide TiO2, indium gallium zinc oxide IGZO, indium tin oxide ITO, indium zinc oxide IZO, etc., with a thickness of 3-20 nm; the channel layer includes a plurality of T-shaped structural grooves, the spacing between adjacent T-shaped structural grooves is L2, ranging from 100 to 1000 nm, the horizontal side length of the T-shaped structural groove is L3, ranging from 100 to 1000 nm; the height of the horizontal side is L5, ranging from 10 to 500 nm, the vertical side height of the T-shaped structural groove is L4, ranging from 10 to 200 nm, and the vertical side width is L1, ranging from 10 to 1000 nm.

[0017] The source electrode and the drain electrode are made of one of Au, Ni / Au, Ni / Au / Ni, and are formed at both ends of the oxide semiconductor channel layer by spin coating photoresist, baking, exposure, development, fixing, oxygen plasma debonding, metal evaporation, and micro-nano processing or shutter mask evaporation. The insulating layer is made of SU-8, PMMA, SiO2, or SiN x .

[0018] The biological probe is a biological probe of DNA or antibody. The modification method of the biological probe is: firstly treat the surface of the oxide semiconductor channel layer with oxygen plasma to form hydroxyl groups on the surface of the channel layer, then modify the amino groups, fix the biological probe of DNA or antibody on the surface of the channel layer, and drip it on the surface of the channel layer modified with amino groups, so that the chemically active groups in DNA and antibody react chemically with amino groups, and then fix the biological probe of DNA or antibody on the surface of the channel layer.

[0019] The preparation method of the sensor is as follows:

[0020] Step 1: Spin-coat a double layer of photoresist on the silicon substrate;

[0021] Step 2: Use ultraviolet exposure or electron beam exposure or nanoimprinting, combined with development, fixing, and residual adhesive removal processes to define the T-shaped structure;

[0022] Step 3: Prepare a T-shaped metal layer by electron beam evaporation process;

[0023] Step 4: Remove the double-layer photoresist;

[0024] Step 5: atomic layer deposition of high-k dielectric layer;

[0025] Step 6: atomic layer deposition of an oxide semiconductor channel layer;

[0026] Step 7: Form metal source and drain electrodes at both ends of the channel layer by a series of micro-nano processing processes or shutter mask evaporation processes such as spin coating photoresist, baking, exposure, development, fixing, oxygen plasma residual glue removal, metal evaporation, and stripping;

[0027] Step 8: Prepare an insulating layer on the metal source and drain.

[0028] The present invention discloses a T-type field effect transistor biosensor based on an atomic layer deposition semiconductor channel. By utilizing the excellent step coverage and precise control of atomic-level film thickness of the atomic layer deposition technology, a high-k dielectric and an oxide semiconductor are sequentially deposited on a three-dimensional T-shaped structure to prepare a three-dimensional T-shaped field effect transistor biosensor. The three-dimensional T-shaped structure device can overcome the influence of the Debye screening effect and achieve a larger Debye length than the planar structure. It can detect low-concentration disease markers in high-ionic strength solutions, has the advantages of high sensitivity and rapid detection, and shows broad application prospects in the fields of instant detection, in vitro diagnosis, biochemical analysis, etc.

[0029] The beneficial effects of the present invention are:

[0030] (1) The growth and device preparation process of oxide semiconductors is fully compatible with existing silicon-based CMOS processes and has great potential for mass production.

[0031] (2) The fabrication process of T-gate structure devices is compatible with silicon-based CMOS process.

[0032] (3) When testing samples with high ionic strength such as blood, urine, and sweat, although the biological molecules exceed the Debye length, the biological molecules are within the Debye length of the side walls and inner walls of the T-shaped structure groove, which can effectively overcome the influence of the Debye length. That is, the T-shaped structure oxide semiconductor channel groove of the present invention can effectively overcome the influence of Debye shielding, further increasing the potential of field effect transistors for clinical sample detection. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] The present invention is further described in detail below with reference to the accompanying drawings and specific embodiments:

[0034] Attached Figure 1 : is a schematic diagram of the structure of the sensor of the present invention (the upper part of the figure is a side view; the lower part of the figure is a top view);

[0035] Attached Figure 2 Schematic diagram of the structure of a T-type oxide semiconductor channel layer (the structure regulates the performance of the T-type field effect transistor by adjusting the sizes of L1, L2, L3, L4, and L5);

[0036] Attached Figure 3 A schematic diagram of the manufacturing process steps of a T-type field effect transistor biosensor based on an atomic layer deposition semiconductor channel;

[0037] Attached Figure 4This is a schematic diagram of the principle of DNA detection by a T-type field effect transistor biosensor based on an atomic layer deposition semiconductor channel (in the figure, a1, a2, a3, a4, and a5 are the Debye lengths of the sample on different surfaces of the T-shaped channel; a6 is the double-stranded DNA formed by the specific binding of the biological probe DNA and the target DNA; when detecting samples with high ionic strength such as blood, urine, and sweat, although the length of the double-stranded DNA exceeds the Debye length, the double-stranded DNA is within the Debye length of the inner wall of the T-shaped structure groove, which can effectively overcome the influence of the Debye length);

[0038] Attached Figure 5 Schematic diagram of the principle of antigen detection by a T-type field effect transistor biosensor based on an atomic layer deposition semiconductor channel (in the figure, b1, b2, b3, b4, and b5 are the Debye lengths of the sample on different surfaces of the T-shaped channel; b6 is the complex of the biological probe antibody and the target antigen, and the antibody specifically captures the antigen; when detecting samples with high ionic strength such as blood, urine, and sweat, although the length of the antibody or antibody-antigen complex exceeds the Debye length, the antibody or antibody-antigen complex is within the Debye length of the inner wall of the T-shaped channel, which can effectively overcome the influence of the Debye length);

[0039] In the figure: 1 is a substrate, 2 is a T-shaped metal layer, 3 is a high-k dielectric layer, 4 is an oxide semiconductor channel layer, 5 is a source-drain metal electrode structure, 6 is an insulating layer, 7 and 9 are lead-out electrodes of the source-drain metal electrode structure 5 (without an insulating layer on the surface, used to connect to a test device), 8 is a lead-out metal electrode of the T-shaped metal layer 2 (without an insulating layer on the surface, used as a gate to connect to a test device), and 10 is an oxide semiconductor channel groove of a T-shaped structure. DETAILED DESCRIPTION

[0040] As shown in the figure, a T-gate FET biosensor based on an atomic layer deposition semiconductor channel comprises a substrate 1, a plurality of T-shaped metal layers 2 are arranged on the surface of the substrate, a high-k dielectric layer 3 is arranged on the substrate and the plurality of T-shaped metal layers, an oxide semiconductor channel layer 4 is arranged on the high-k dielectric layer, source-drain metal electrode structures 5 that can be used as source electrodes or drain electrodes are arranged at both ends of the channel layer, and an insulating layer 6 is arranged on the source electrode and the drain electrode;

[0041] The ITO channel layer includes a T-shaped channel groove 10, the surface of which is modified with a biological probe for specifically capturing target biological molecules;

[0042] The biological probe is confined within the Debye length of the inner wall of the T-shaped structural groove to overcome the influence of the Debye length in the detection process.

[0043] The substrate comprises a silicon wafer. When preparing a T-shaped metal layer spaced apart on the surface of the substrate, a double-layer photoresist structure with a plurality of T-shaped grooves spaced apart on the surface of the substrate silicon wafer is first prepared. The method comprises:

[0044] Method A: sequentially performing spin coating of a double-layer photoresist, baking, ultraviolet exposure, development, fixing, and oxygen plasma residual resist removal processes on a substrate;

[0045] Method B, sequentially performing spin coating of a double-layer photoresist, baking, electron beam exposure, and oxygen plasma residual resist removal processes on a substrate;

[0046] Method C, sequentially performing spin coating of a double-layer photoresist, baking, nano-imprinting, developing, fixing, and oxygen plasma residual resist removal processes on a substrate.

[0047] The double-layer photoresist is composed of two types of photoresists with different sensitivities to ultraviolet light and electron dose. The photoresist in contact with the silicon wafer is the bottom layer photoresist, and the sensitivity of the bottom layer photoresist to ultraviolet light or electron dose is lower than that of the upper layer photoresist. The size of the T-shaped structure is controlled by changing the type, thickness, and exposure conditions of the double-layer photoresist, thereby regulating the performance of the T field effect transistor biosensor.

[0048] The material used for the T-shaped metal layer is one or more of Cr, Ti, Al, Ni, Au, and Pt.

[0049] The high-k dielectric layer is Al2O3, HfO2, ZrO2, La2O3, HfAlOx, HfSiO x 、HfLaO x 、HfZrO x , HfSiON high-k dielectric, and one or more thereof, prepared by atomic layer deposition with a thickness of 5-20 nm.

[0050] The oxide semiconductor channel layer is prepared by atomic layer deposition, and the oxide semiconductor channel layer adopts one or more of zinc oxide ZnO, indium oxide In2O3, tin oxide SnO2, gallium oxide Ga2O3, titanium oxide TiO2, indium gallium zinc oxide IGZO, indium tin oxide ITO, and indium zinc oxide IZO oxide semiconductor materials, with a thickness of 3-20nm. The channel layer includes a plurality of T-shaped structural grooves, and the spacing between adjacent T-shaped structural grooves is L2, ranging from 100 to 1000 nm, the horizontal side length of the T-shaped structural groove is L3, ranging from 100 to 1000nm; the height of the horizontal side is L5, ranging from 10 to 500 nm, the vertical side height of the T-shaped structural groove is L4, ranging from 10 to 200nm, and the vertical side width is L1, ranging from 10 to 1000 nm.

[0051] The source electrode and the drain electrode are made of one of Au, Ni / Au, Ni / Au / Ni, and are formed at both ends of the channel layer by spin coating photoresist, baking, exposure, development, fixing, oxygen plasma debonding, metal evaporation, and micro-nano processing or shutter mask evaporation. The insulating layer is made of SU-8, PMMA, SiO2, or SiN x .

[0052] The biological probe is a biological probe of DNA or antibody. The modification method of the biological probe is: firstly treat the surface of the channel layer with oxygen plasma to form hydroxyl groups on the surface of the channel layer, then modify the amino groups, fix the biological probe of DNA or antibody on the surface of the channel layer, and drip it on the surface of the channel layer modified with amino groups, so that the chemically active groups in DNA and antibody react chemically with amino groups, and then fix the biological probe of DNA or antibody on the surface of the channel layer.

[0053] The preparation method of the sensor is as follows:

[0054] Step 1: Spin-coat a double layer of photoresist on the silicon substrate;

[0055] Step 2: Using ultraviolet exposure or electron beam exposure or nanoimprinting, combined with development, fixing, and degumming processes, to define the T-shaped structure;

[0056] Step 3: Prepare a T-shaped metal layer by electron beam evaporation process;

[0057] Step 4: Remove the double-layer photoresist;

[0058] Step 5: atomic layer deposition of high-k dielectric layer;

[0059] Step 6: atomic layer deposition of an oxide semiconductor channel layer;

[0060] Step 7: Form metal source and drain electrodes at both ends of the channel layer by a series of micro-nano processing processes or shutter mask evaporation processes such as spin coating photoresist, baking, exposure, development, fixing, oxygen plasma residual glue removal, metal evaporation, and stripping;

[0061] Step 8: Prepare an insulating layer on the metal source and drain.

[0062] Specifically:

[0063] Step S1, cleaning the substrate silicon. The silicon wafer is P-type and doped with boron (B), and the resistance is less than 0.005 ohms. Use the standard RCA1 cleaning process to remove particles and organic matter on the substrate. After cleaning, blow dry with high-purity nitrogen gas for standby use.

[0064] Step S2, spin coating a double layer of photoresist on the silicon substrate, using one of the following two methods;

[0065] Method A: The bottom layer photoresist is 495PMMA A resists (Microchem, solid content 6%), and the spin coating process parameters are: accelerating from 0 rpm to 3000 rpm within 5 s, maintaining 3000 rpm for 30 s, and baking on a hot plate at 180 °C for 60 s;

[0066] Method B: The bottom layer photoresist is Copolymer resists (Microchem, solid content 9%), and the spin coating process parameters are: accelerate from 0 rpm to 3500 rpm within 5 seconds, maintain 3500 rpm for 30 seconds, and bake on a hot plate at 150°C for 60 seconds;

[0067] Step S3: electron beam exposure. Electron beam exposure parameters: voltage 30 kV, electron beam dose 150 μC / cm 2 ;

[0068] Step S4, development, post-baking, and degumming, specifically includes:

[0069] (1) The developer is a mixture of MIBK and IPA in a volume ratio of 1:3. The sample after electron beam exposure is immersed in the developer. The development temperature is 21°C and the development time is 10 s. After the development is completed, the sample is immersed in deionized water for cleaning and blown dry with nitrogen.

[0070] (2) Post-baking, used to remove residual developer and water, baking on a hot plate at 100°C for 60 seconds;

[0071] (3) Remove the glue using Remover PG (Microchem) at a temperature of 21°C for about 60 seconds. After degumming, rinse the sample in deionized water and dry it with nitrogen.

[0072] Step S5, preparing a T-shaped metal layer by uniform electron beam evaporation and stripping process, wherein the metals are 10 nm Ni and 150 nm Au. After the preparation of the T-shaped metal layer is completed, the double-layer photoresist is removed by acetone;

[0073] Step S6, using an atomic layer deposition system to grow a 5 nm thick high-k dielectric layer HfO2 as a gate dielectric on the substrate silicon and the T-shaped metal layer. TEMAHf and O3 are used as precursors during the growth, and gaseous precursor pulses are alternately introduced into the reaction chamber through the carrier gas N2 for growth, and the growth temperature is 250°C;

[0074] Step S7, using an atomic layer deposition system to grow indium tin oxide ITO with a thickness of 10 nm on the high-k dielectric layer HfO2; the indium precursor used is trimethyl indium (TMIn), the tin precursor is tetrakis (dimethylamino) tin (TDMASn), the oxygen source is plasma O2, the growth temperature is 200 ° C, and the composition ratio of indium oxide InOx to tin oxide SnOx is about 9:1;

[0075] The size of the T-shaped structure: L1 is about 30-40 nm, L2 is about 200 nm, L3 is about 200 nm, L4 is about 40-50 nm, and L5 is about 30-40 nm;

[0076] Step S8, preparing the source electrode and the drain electrode by photoresist, exposure, development, electron beam evaporation and stripping process, the contact metal is 15 nm Ni and 20 nm Au; the source electrode and the drain electrode are composed of 5-10 nm Cr and 30-50 nm Au, and the ITO channel length is 20 μm and the width is 50 μm;

[0077] Step S9, coating, baking, exposure, development, fixing, and degumming process, forming an insulating layer on the source electrode and the drain electrode to isolate the source electrode and the drain electrode from contact with the test sample, specifically:

[0078] (1) Spin coating SU-8, the spin coating parameters are 800 rpm / 3 s, 3000 rpm / 30 s, and bake at 110 °C for 3 min after spin coating;

[0079] (2) Exposure for 6 s, baking at 110 °C for 2 min;

[0080] (3) PGMEA development for 60 s, IPA development for 30 s. Rinse with deionized water and blow dry with nitrogen;

[0081] Step S10: fix the DNA probe, specifically:

[0082] (1) The device was treated with oxygen plasma. The ITO surface was hydroxyl-containing. The ratio of argon to oxygen was 4:1, the power was 15 W, and the treatment time was 5 min.

[0083] (2) Immerse the device treated with oxygen plasma in an APTES solution with a concentration of 2% and a solvent of a mixture of anhydrous ethanol and water with a water content of 5%; react at room temperature for 3 hours. After the reaction is completed, clean the device with anhydrous ethanol and deionized water, and blow dry with nitrogen for later use;

[0084] (3) Prepare a 2 μmol / mL DNA probe with a 1× PBS buffer solution at pH = 7.4, and fix it on the ITO using the EDC / NHS method; the concentration of EDC is 2 mmol / L, and the concentration of NHS is 10 mmol / L; react at room temperature in the dark for 0.5 h; after the reaction, clean the device with a 1× PBS buffer solution at pH = 7.4, blow dry with nitrogen gas and set aside.

[0085] Embodiment 1:

[0086] DNA testing

[0087] DNA probe sequence:

[0088] COOH-5'-TTTTTTCCATAACCTTTCCACATACCGCAGACGG-3';

[0089] DNA target sequence:

[0090] 5'-CCGTCTGCGGTATGTGGAAAGGTTATGG-3';

[0091] The DNA probe and DNA target were synthesized by Shanghai Shenggong Bioengineering Co., Ltd.

[0092] A T-type field effect transistor biosensor based on atomic layer deposition semiconductor channel, the sensor comprises a substrate 1, a plurality of T-shaped metal structures 2 are arranged on the surface of the substrate 1, a high-k dielectric layer 3 is arranged on the substrate 1 and the T-shaped metal structure 2, an ITO channel layer 4 is arranged on the high-k dielectric layer 3, a source electrode and a drain electrode 5 are arranged at both ends of the ITO channel layer 3, and an insulating layer 6 is arranged on the source electrode and the drain electrode 5; the following is a method for preparing the sensor:

[0093] 1. Clean the substrate silicon. The silicon wafer is P-type and doped with boron (B), with a resistance of less than 0.005 ohms. Use the standard RCA1 cleaning process to remove particles and organic matter on the substrate. After cleaning, blow dry with high-purity nitrogen and set aside.

[0094] 2. Spin-coat a double layer of photoresist on the substrate silicon. (1) The bottom photoresist is 495PMMA A6 resists (Microchem, solid content 6%), and the spin coating process parameters are: accelerate from 0 rpm to 3000 rpm within 5 seconds, and maintain 3000 rpm for 30 seconds. Bake on a hot plate at 180 °C for 60 seconds. (2) The bottom photoresist is Copolymer resists (Microchem, solid content 9%), and the spin coating process parameters are: accelerate from 0 rpm to 3500 rpm within 5 seconds, and maintain 3500 rpm for 30 seconds. Bake on a hot plate at 150 °C for 60 seconds.

[0095] 3. Electron beam exposure. Electron beam exposure parameters: voltage 30 kV, electron beam dose 150 μC / cm 2 .

[0096] 4. Development, post-baking, and degumming. (1) The developer is a mixture of MIBK and IPA in a volume ratio of 1:3. The sample after electron beam exposure is immersed in the developer. The development temperature is 21 °C and the development time is 10 s. After the development is completed, the sample is immersed in deionized water for cleaning and blown dry with nitrogen. (2) Post-baking. To remove residual developer, water, etc., bake on a hot plate at 100 °C for 60 s. (3) Use the degumming solution Remover PG (Microchem) for degumming. The degumming temperature is 21 °C and the degumming time is about 60 s. After degumming, the sample is immersed in deionized water for cleaning and blown dry with nitrogen.

[0097] 5. Prepare the T-shaped metal layer by uniform electron beam evaporation and lift-off process, using 10 nm Ni and 150 nm Au as the metal. After the T-shaped metal layer is prepared, remove the double-layer photoresist with acetone.

[0098] 6. A 5 nm thick high-k dielectric layer HfO2 was grown on the substrate silicon and T-shaped metal layer using an atomic layer deposition system as a gate dielectric. TEMAHf and O3 were used as precursors during the growth, and gaseous precursor pulses were alternately introduced into the reaction chamber through the carrier gas N2 for growth at a growth temperature of 250 °C.

[0099] 7. An atomic layer deposition system was used to grow 10 nm thick ITO on the high-k dielectric layer HfO2. The indium precursor used was trimethyl indium (TMIn), the tin precursor was tetrakis(dimethylamino)tin (TDMASn), the oxygen source was plasma O2, the growth temperature was 200 °C, and the composition ratio of indium oxide InOx to tin oxide SnOx was about 9:1. The dimensions of the T-shaped structure: L1 is about 30-40nm, L2 is about 200nm, L3 is about 200nm, L4 is about 40-50nm, and L5 is about 30-40nm.

[0100] 8. The source and drain electrodes are prepared by photoresist, exposure, development, electron beam evaporation and stripping processes. The metals used are 15 nm Ni and 20 nm Au. The source and drain electrodes are composed of 5-10 nm Cr and 30-50 nm Au. The ITO channel is 20 μm long and 50 μm wide.

[0101] 9. After the process steps of coating, baking, exposure, development, fixing, and debonding, an insulating layer is formed on the source electrode and the drain electrode to isolate the source electrode and the drain electrode from contact with the test sample. (1) Spin coating SU-8, the coating parameters are 800 rpm / 3s, 3000 rpm / 30s, and bake at 110℃ for 3min after spin coating. (2) Expose for 6s, bake at 110℃ for 2min. (3) PGMEA development for 60s, IPA development for 30s. Rinse with deionized water and blow dry with nitrogen.

[0102] 10. Fixing DNA probes. (1) Treat the device with oxygen plasma. The ratio of argon to oxygen is 4:1. The power is 15 W and the treatment time is 5 min. (2) Soak the device treated with oxygen plasma in an APTES solution. The concentration of APTES is 2%. The solvent is a mixture of anhydrous ethanol and water. The water content is 5%. The reaction is carried out at room temperature for 3 hours. After the reaction is completed, the device is cleaned with anhydrous ethanol and deionized water, and dried with nitrogen gas for later use. (3) Prepare a 2 μmol / mL DNA probe with a 1× PBS buffer solution at pH=7.4, and fix it on ITO using the EDC / NHS method. The concentration of EDC is 2 mmol / L, and the concentration of NHS is 10 mmol / L. The reaction is carried out at room temperature in the dark for 0.5 hour. After the reaction is completed, the device is cleaned with a 1× PBS buffer solution at pH=7.4, and dried with nitrogen gas for later use.

[0103] 11. Prepare target DNA with different concentrations of 10 pmol / L, 100 pmol / L, and 1 nmol / L in 1× PBS buffer solution with pH=7.4. In 1× PBS buffer solution, the Debye length of the ITO interface is about 1 nm, which is much smaller than the length of the DNA probe and the target DNA. First, drip 100 μL of 1× PBS buffer solution on the device and let it stand for 2 hours. Then drip 10 μL of target DNA solution in turn and start the test. The test parameters are: gate voltage V g = -0.1V, source-drain voltage V d = 50 mV, test channel current I d -t curve.

[0104] Embodiment 2:

[0105] Detect COVID-19 IgG (COVID-19-IgG).

[0106] The N protein (COVID-19-N) of COVID-19 was used as a probe to specifically capture COVID-19 IgG. The COVID-19-N and COVID-19-IgG were purchased from Nearshore Protein Technology Co., Ltd.

[0107] A T-type field effect transistor biosensor based on atomic layer deposition semiconductor channel, the sensor comprises a substrate 1, a plurality of T-shaped metal structures 2 are arranged on the surface of the substrate 1, a high-k dielectric layer 3 is arranged on the substrate 1 and the T-shaped metal structure 2, an ITO channel layer 4 is arranged on the high-k dielectric layer 3, a source electrode and a drain electrode 5 are arranged at both ends of the ITO channel layer 3, and an insulating layer 6 is arranged on the source electrode and the drain electrode 5; the following is a method for preparing the sensor:

[0108] 1. Clean the substrate silicon. The silicon wafer is P-type and doped with boron (B), with a resistance of less than 0.005 ohms. Use the standard RCA1 cleaning process to remove particles and organic matter on the substrate. After cleaning, blow dry with high-purity nitrogen and set aside.

[0109] 2. Spin-coat a double layer of photoresist on the substrate silicon. (1) The bottom photoresist is 950PMMA C resists (Microchem, solid content 10%), and the spin coating process parameters are: accelerate from 0 rpm to 2000 rpm within 5 s, and keep at 2000 rpm for 30 s. Bake on a hot plate at 180℃ for 60 s. (2) The bottom photoresist is Copolymer resists (Microchem, solid content 11%), and the spin coating process parameters are: accelerate from 0 rpm to 2000 rpm within 5 s, and keep at 2000 rpm for 30 s. Bake on a hot plate at 150℃ for 60 s.

[0110] 3. Electron beam exposure. Electron beam exposure parameters: voltage 30 kV, electron beam dose 150 μC / cm 2 .

[0111] 4. Development, post-baking, and degumming. (1) The developer is a mixture of MIBK and IPA in a volume ratio of 1:3. The sample after electron beam exposure is immersed in the developer. The development temperature is 21 °C and the development time is 10 s. After the development is completed, the sample is immersed in deionized water for cleaning and blown dry with nitrogen. (2) Post-baking. To remove residual developer, water, etc., bake on a hot plate at 100 °C for 60 s. (3) Use the degumming solution Remover PG (Microchem) for degumming. The degumming temperature is 21 °C and the degumming time is about 60 s. After degumming, the sample is immersed in deionized water for cleaning and blown dry with nitrogen.

[0112] 5. Prepare the T-shaped metal layer by uniform electron beam evaporation and lift-off process, using 10 nm Ni and 150 nm Au as the metal. After the T-shaped metal layer is prepared, remove the double-layer photoresist with acetone.

[0113] 6. A 5 nm thick high-k dielectric layer HfO2 was grown on the substrate silicon and T-shaped metal layer using an atomic layer deposition system as a gate dielectric. TEMAHf and O3 were used as precursors during the growth, and gaseous precursor pulses were alternately introduced into the reaction chamber through the carrier gas N2 for growth at a growth temperature of 250 °C.

[0114] 7. An atomic layer deposition system was used to grow 10 nm thick ITO on the high-k dielectric layer HfO2. The indium precursor used was trimethyl indium (TMIn), the tin precursor was tetrakis(dimethylamino)tin (TDMASn), the oxygen source was plasma O2, the growth temperature was 200 °C, and the composition ratio of indium oxide InOx to tin oxide SnOx was about 9:1. The dimensions of the T-shaped structure: L1 was about 100 nm, L2 was about 200 nm, L3 was about 200 nm, L4 was about 80-100 nm, and L5 was about 300-350 nm.

[0115] 8. The source and drain electrodes are prepared by photoresist, exposure, development, electron beam evaporation and stripping processes. The metals are 15 nm Ni and 20 nm Au. The source and drain electrodes are composed of 5-10 nm Cr and 30-50 nm Au. The ITO channel is 20 μm long and 50 μm wide.

[0116] 9. After the process steps of coating, baking, exposure, development, fixing, and debonding, an insulating layer is formed on the source electrode and the drain electrode to isolate the source electrode and the drain electrode from contact with the test sample. (1) Spin coating SU-8, the coating parameters are 800 rpm / 3 s, 3000 rpm / 30 s, and bake at 110 ℃ for 3 min after spin coating. (2) Expose for 6 s, bake at 110 ℃ for 2 min. (3) PGMEA development for 60 s, IPA development for 30 s. Rinse with deionized water and blow dry with nitrogen.

[0117] 10. Fix the COVID-19-N probe. (1) Treat the device with oxygen plasma. The ITO surface has hydroxyl groups. The ratio of argon to oxygen is 4:1, the power is 15 W, and the treatment time is 5 min. (2) Soak the device treated with oxygen plasma in APTES solution. The concentration of APTES is 2%. The solvent is a mixture of anhydrous ethanol and water, and the water content is 5%. React at room temperature for 3 hours. After the reaction is completed, clean the device with anhydrous ethanol and deionized water, and blow dry with nitrogen for use. (3) Prepare 20 g / mL COVID-19-N probe was fixed on ITO using the EDC / NHS method. The concentration of EDC was 2mmol / L and the concentration of NHS was 10 mmol / L. The reaction was carried out at room temperature and protected from light for 0.5 hours. After the reaction, the device was cleaned with 1× PBS buffer solution with a pH of 7.4 and dried with nitrogen for later use. 2% BSA was added dropwise on the ITO surface and incubated at room temperature for 30 min. The surface was then cleaned with 1× PBS buffer solution and dried with nitrogen gas for later use.

[0118] 11. Prepare COVID-19-IgG at different concentrations of 1 pg / mL, 10 pg / mL, and 1 ng / mL using 1× PBS buffer solution at pH 7.4. First, add 100 L 1× PBS buffer solution was placed on the device and allowed to stand for 2 hours. Then 10 μL of COVID-19-IgG solution was added dropwise and the test was started. The test parameters were: back gate voltage Vg = -0.1V, source-drain voltage Vd = 50 mV, and the channel current Id-t curve was tested.

Claims

1. A T-gate FET biosensor based on an atomic layer deposition semiconductor channel, characterized in that: The sensor comprises a substrate, a plurality of T-shaped metal layers are arranged on the surface of the substrate, a high-k dielectric layer is coated on the substrate and the plurality of T-shaped metal layers, an oxide semiconductor channel layer is coated on the high-k dielectric layer, source-drain metal electrode structures that can be used as source electrodes or drain electrodes are arranged at both ends of the channel layer, and an insulating layer is arranged on the source electrode and the drain electrode; The channel layer comprises an oxide semiconductor channel groove in a T-shaped structure, and the surface of the channel layer is modified with a biological probe for specifically capturing target biological molecules; The biological probe is confined within the Debye length of the inner wall of the T-shaped oxide semiconductor channel to overcome the influence of Debye shielding during the detection process; The substrate comprises a silicon wafer. When preparing a T-shaped metal layer spaced apart on the surface of the substrate, a double-layer photoresist structure with a plurality of T-shaped grooves spaced apart on the surface of the substrate silicon wafer is first prepared. The method comprises: Method A: sequentially performing spin coating of a double-layer photoresist, baking, ultraviolet exposure, development, fixing, and oxygen plasma residual resist removal processes on a substrate; Method B, sequentially performing spin coating of a double-layer photoresist, baking, electron beam exposure, and oxygen plasma residual resist removal processes on a substrate; Method C, sequentially performing spin coating of a double-layer photoresist, baking, nanoimprinting, developing, fixing, and oxygen plasma residual photoresist removal processes on a substrate; The double-layer photoresist is two types of photoresists with different sensitivities to ultraviolet light and electron doses, the photoresist in contact with the silicon wafer is the bottom layer photoresist, and the sensitivity of the bottom layer photoresist to ultraviolet light or electron dose is lower than that of the upper layer photoresist; By changing the type, thickness, and exposure conditions of the double-layer photoresist, the size of the T-shaped structure can be controlled, thereby regulating the performance of the T field effect transistor biosensor; The material used for the T-shaped metal layer is one or more of Cr, Ti, Al, Ni, Au, and Pt; The high-k dielectric layer is Al2O3, HfO2, ZrO2, La2O3, HfAlOx, HfSiO x 、HfLaO x 、HfZrO x , one or more of HfSiON high-k dielectrics, prepared by atomic layer deposition, with a thickness of 5-20 nm; The oxide semiconductor channel layer is prepared by atomic layer deposition, and the oxide semiconductor channel layer adopts one or more of zinc oxide ZnO, indium oxide In2O3, tin oxide SnO2, gallium oxide Ga2O3, titanium oxide TiO2, indium gallium zinc oxide IGZO, indium tin oxide ITO, indium zinc oxide IZO oxide semiconductor materials, and has a thickness of 3-20 nm; the oxide semiconductor channel layer includes a plurality of T-shaped structural grooves, the spacing between adjacent T-shaped structural grooves is L2, ranging from 100 to 1000 nm, the horizontal length of the T-shaped structural groove is L3, ranging from 100 to 1000 nm; the height of the horizontal side is L5, ranging from 10 to 500 nm, the vertical side height of the T-shaped structural groove is L4, ranging from 10 to 200 nm, and the vertical side width is L1, ranging from 10 to 1000 nm; The source electrode and the drain electrode are made of one of Au, Ni / Au, and Ni / Au / Ni, and are formed at both ends of the channel layer by spin coating photoresist, baking, exposure, development, fixing, oxygen plasma residual glue removal, metal evaporation, and micro-nano processing or shutter mask evaporation. The material of the insulating layer is SU-8, PMMA, SiO2 or SiN x ; The biological probe is a DNA or antibody biological probe, and the modification method of the biological probe is: firstly treat the surface of the ITO channel layer with oxygen plasma to form hydroxyl groups on the surface of the ITO channel layer, then modify the amino groups, fix the DNA or antibody biological probe on the surface of the channel layer, and drip it on the surface of the channel layer modified with the amino groups, so that the chemically active groups in the DNA and the antibody react chemically with the amino groups, and then fix the DNA or antibody biological probe on the surface of the channel layer; When detecting biomolecule samples with high ionic strength, the T-shaped oxide semiconductor trench overcomes the Debye screening effect by using a sidewall Debye length or an inner wall Debye length that is greater than the length of the biomolecule.

2. The T-gate FET biosensor based on atomic layer deposition semiconductor channel according to claim 1, characterized in that: The preparation method of the sensor is as follows: Step 1: Spin-coat a double layer of photoresist on the silicon substrate; Step 2: Use ultraviolet exposure or electron beam exposure or nanoimprinting, combined with development, fixing, and residual adhesive removal processes to define the T-shaped structure; Step 3: Prepare a T-shaped metal layer by electron beam evaporation process; Step 4: Remove the double-layer photoresist; Step 5: atomic layer deposition of high-k dielectric layer; Step 6: atomic layer deposition of an oxide semiconductor channel layer; Step 7: Form metal source and drain contact electrodes at both ends of the channel layer through a series of micro-nano processing processes or shutter mask evaporation processes such as spin coating photoresist, baking, exposure, development, fixing, oxygen plasma residual glue removal, metal evaporation, and stripping; Step 8: Prepare an insulating layer on the metal source and drain electrodes.

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