阅读说明：本技术 一种Ni3(HITP)2场效应晶体管生物传感器及其制备方法 (Ni3(HITP)2Field effect transistor biosensor and preparation method thereof ) 是由 段国韬 沈树阳 谭彭伟 唐宇枢 于 2021-08-27 设计创作，主要内容包括：本发明属于生物传感器领域,公开了一种Ni-(3)(HITP)-(2)场效应晶体管生物传感器及其制备方法,该制备方法是基于Ni-(3)(HITP)-(2)场效应晶体管,先制备溶液液槽,使液槽内溶液能够与晶体管的沟道区域相接触,随后将戊二醛交联剂修饰至沟道区域材料表面,再将新冠病毒抗原蛋白探针分子通过戊二醛交联剂固定至沟道材料表面,由此得到Ni-(3)(HITP)-(2)场效应晶体管生物传感器；该液槽能够容纳待测液体,利用生物传感器的电学性能变化,实现对待测液体中新型冠状病毒抗体分子检测。本发明通过对生物传感器的细节结构进行设计改进,得到的生物传感器能够实现对新型冠状病毒抗体分子(尤其是低浓度新型冠状病毒抗体分子)的快速灵敏检测,检测限低至10pg/mL。(The invention belongs to the field of biosensors and discloses Ni 3 (HITP) 2 A field effect transistor biosensor and a method for preparing the same, the method for preparing the same is based on Ni 3 (HITP) 2 Preparing a solution liquid tank, enabling the solution in the liquid tank to be in contact with a channel region of the transistor, modifying a glutaraldehyde crosslinking agent to the surface of a channel region material, and fixing new coronavirus antigen protein probe molecules to the surface of the channel material through the glutaraldehyde crosslinking agent to obtain Ni 3 (HITP) 2 A field effect transistor biosensor; the liquid tank can contain liquid to be detected, and the detection of the novel coronavirus antibody molecules in the liquid to be detected is realized by utilizing the change of the electrical property of the biosensor. The invention relates to a biosensorThe detail structure of the biosensor is improved in design, and the obtained biosensor can realize rapid and sensitive detection of novel coronavirus antibody molecules (particularly low-concentration novel coronavirus antibody molecules), and the detection limit is as low as 10 pg/mL.)

1. Ni₃(HITP)₂A method for manufacturing a field effect transistor biosensor, characterized in that the method is based on Ni₃(HITP)₂Field effect transistor, first of all, of the Ni₃(HITP)₂Preparing a solution tank for containing the liquid to be measured in the channel region of the field effect transistor so that the liquid to be measured can be mixed with the Ni₃(HITP)₂Contacting channel region sensitive materials of the field effect transistor, and modifying glutaraldehyde crosslinking agent to channel region Ni₃(HITP)₂Fixing new coronavirus antigen protein probe molecules on the surface of the material to a channel region Ni through a glutaraldehyde cross-linking agent₃(HITP)₂On the surface of the material, Ni is obtained₃(HITP)₂A field effect transistor biosensor; the Ni₃(HITP)₂The field effect transistor biosensor can contain the liquid to be measured in the solution tank and use the Ni₃(HITP)₂And (3) judging whether the liquid to be detected contains the novel coronavirus antibody molecules or not by changing the electrical property of the field effect transistor biosensor, thereby realizing the detection of the novel coronavirus antibody molecules.

2. The method of claim 1, wherein the Ni is₃(HITP)₂The field effect transistor biosensor can apply fixed gate voltage and source-drain currentAnd (3) measuring the change of a source drain terminal current signal, thereby realizing the detection of the novel coronavirus antibody molecule.

3. The method of claim 1, wherein the glutaraldehyde cross-linking agent is modified to channel region Ni₃(HITP)₂Fixing new coronavirus antigen protein probe molecules on the surface of the material to a channel region Ni through a glutaraldehyde cross-linking agent₃(HITP)₂The surface of the material is, in particular:

dropwise adding a glutaraldehyde solution into the solution tank for cultivation, wherein the cultivation temperature is 25 ℃, and the cultivation time is 1-2 h; after the culture is finished, sucking away the glutaraldehyde solution, then dropwise adding the new crown antigen molecule solution into the solution liquid tank for culture, wherein the culture temperature is 0-4 ℃, and the culture time is 8-12 h.

4. The preparation method according to claim 3, wherein the mass percentage concentration of glutaraldehyde in the glutaraldehyde solution is 0.10-0.50%; the concentration of the neocorona antigen molecules in the neocorona antigen molecule solution is 100-200 mug/mL.

5. The method according to claim 1, wherein the solution tank is a PDMS solution tank; preferably, the PDMS solution liquid tank is formed by curing Polydimethylsiloxane (PDMS) at 20-25 ℃;

the PDMS solution liquid groove is a cylinder, the inner diameter of the cross section of the PDMS solution liquid groove is 3-4 mm, and the height of the cylinder is 1-1.5 mm.

6. The method according to claim 3, wherein the solution tank is capable of holding a volume of 20 to 30 μ L of liquid;

the volume of the glutaraldehyde solution is 15-25 mu L; the volume of the neocorona antigen molecule solution is 15-25 mu L.

7. Ni produced by the production method according to any one of claims 1 to 6₃(HITP)₂A field effect transistor biosensor.

Technical Field

Hair brushBelongs to the field of biosensors, and particularly relates to Ni₃(HITP)₂A field effect transistor biosensor and a preparation method thereof are provided, and the biosensor can be applied to novel coronavirus detection.

Background

The Metal Organic Framework (MOF) is an organic-inorganic hybrid material with adjustable structure formed by self-assembly of organic ligands and metal centers, has the advantages of adjustable structure, large specific surface area, many active adsorption sites and the like, and is widely applied to the fields of gas storage and separation, catalysis, sensing and the like. In the traditional MOF materials, most of them have the defect of poor conductivity, which limits their application in electronic devices, but with the successful preparation of conductive MOF materials, electronic devices based on two-dimensional conductive MOF materials become a hot research.

The novel coronavirus pneumonia is a novel infectious disease which is outbreak and gradually spread from the early 2020, the main basis for the accurate diagnosis of the novel coronavirus is virus nucleic acid detection, and immunological detection serving as an auxiliary method is also one of aetiological evidences for accurate diagnosis. The immunological detection mainly comprises the detection of antibody molecules of the new coronavirus. However, the traditional immunological detection methods such as colloidal gold method and enzyme-linked immunosorbent assay have the limitations of complex operation, long detection time, inconvenience in carrying and the like. Therefore, it is necessary to develop a method for detecting an antibody and a corresponding device, which are fast and sensitive in monitoring, simple in operation and easy to carry.

The sensing detection method based on the field effect transistor has the advantages of high detection speed, high sensitivity, simplicity in operation, easiness in carrying and the like, and is a novel, quick and effective detection method. The inventor of the present invention obtained Chinese patent application CN110429032A through earlier research of subject group, wherein the invention discloses a Ni-based alloy₃(HITP)₂A conductive MOF film field effect transistor and a preparation method thereof. However, in the prior art, a MOF-based field effect transistor biosensor for realizing convenient and sensitive detection of new coronavirus antibody molecules has not yet been developed.

Disclosure of Invention

The above deficiencies and needs in the art are addressed by the present inventionIn providing a Ni₃(HITP)₂A field effect transistor biosensor and a method for manufacturing the same, based on Ni by improving the design of the detail structure of the biosensor₃(HITP)₂The biosensor capable of detecting the novel coronavirus antibody molecules is prepared by the field effect transistor, and the specific combination of the molecules to be detected and the probe molecules is utilized to change the electrical signals of the sensor, so that the sensitive and specific detection of the sensor on the novel coronavirus antibody molecules (especially the novel coronavirus antibody molecules with low concentration) is realized, and the detection limit is as low as 10 pg/mL. The biosensor is used for detecting novel coronavirus antibody molecules, a quick, simple and convenient novel method is provided for virus detection, and the sensor has wide application prospects in the fields of clinical medicine and the like due to the characteristics of sensitivity, quick response, good selectivity and the like.

To achieve the above object, according to one aspect of the present invention, there is provided Ni₃(HITP)₂A method for manufacturing a field effect transistor biosensor, characterized in that the method is based on Ni₃(HITP)₂Field effect transistor, first of all, of the Ni₃(HITP)₂Preparing a solution tank for containing the liquid to be measured in the channel region of the field effect transistor so that the liquid to be measured can be mixed with the Ni₃(HITP)₂Contacting channel region sensitive materials of the field effect transistor, and modifying glutaraldehyde crosslinking agent to channel region Ni₃(HITP)₂Fixing new coronavirus antigen protein probe molecules on the surface of the material to a channel region Ni through a glutaraldehyde cross-linking agent₃(HITP)₂On the surface of the material, Ni is obtained₃(HITP)₂A field effect transistor biosensor; the Ni₃(HITP)₂The field effect transistor biosensor can contain the liquid to be measured in the solution tank and use the Ni₃(HITP)₂And (3) judging whether the liquid to be detected contains the novel coronavirus antibody molecules or not by changing the electrical property of the field effect transistor biosensor, thereby realizing the detection of the novel coronavirus antibody molecules.

As a further aspect of the inventionPreferably, the Ni₃(HITP)₂The field effect transistor biosensor can measure the change of a source drain terminal current signal by applying a fixed grid voltage and a source drain voltage, thereby realizing the detection of novel coronavirus antibody molecules.

As a further preference of the invention, the glutaraldehyde crosslinking agent is modified to channel region Ni₃(HITP)₂Fixing new coronavirus antigen protein probe molecules on the surface of the material to a channel region Ni through a glutaraldehyde cross-linking agent₃(HITP)₂The surface of the material is, in particular:

dropwise adding a glutaraldehyde solution into the solution tank for cultivation, wherein the cultivation temperature is 25 ℃, and the cultivation time is 1-2 h; after the culture is finished, sucking away the glutaraldehyde solution, then dropwise adding the new crown antigen molecule solution into the solution liquid tank for culture, wherein the culture temperature is 0-4 ℃, and the culture time is 8-12 h.

According to further optimization of the invention, the mass percentage concentration of the glutaraldehyde in the glutaraldehyde solution is 0.10-0.50%; the concentration of the neocorona antigen molecules in the neocorona antigen molecule solution is 100-200 mug/mL.

As a further preferred aspect of the present invention, the solution tank is specifically a PDMS solution tank; preferably, the PDMS solution liquid tank is formed by curing Polydimethylsiloxane (PDMS) at 20-25 ℃;

the PDMS solution liquid groove is a cylinder, the inner diameter of the cross section of the PDMS solution liquid groove is 3-4 mm, and the height of the cylinder is 1-1.5 mm.

In a further preferred embodiment of the present invention, the volume of the liquid that can be contained in the solution tank is 20 to 30 μ L;

the volume of the glutaraldehyde solution is 15-25 mu L; the volume of the neocorona antigen molecule solution is 15-25 mu L.

According to another aspect of the present invention, the present invention provides Ni prepared by the above-mentioned preparation method₃(HITP)₂A field effect transistor biosensor.

Through the technical scheme, compared with the prior art, the invention has the following beneficial effects:

MOF materials are diverse, but conductive MOF materials are less common. The present invention focuses on conductive MOF materials, utilizing Ni₃(HITP)₂The conductive MOF-based field effect transistor formed by the MOF material with better conductivity further obtains an MOF-FET biosensor, and is particularly applicable to new crown detection. The invention is based on Ni₃(HITP)₂The conductive MOF-based field effect transistor channel region is prepared by first preparing a solution reservoir for holding a liquid (e.g., a reservoir for storing an analyte solution to be tested can be prepared using Polydimethylsiloxane (PDMS)), and then a channel material (i.e., Ni) within the reservoir₃(HITP)₂Material) surface sequentially modifies glutaraldehyde linking molecules and antigen protein probe molecules (the antigen protein probe molecules are fixed on the surface of the channel material through chemical bonding with glutaraldehyde), and the specific sensitive detection of novel coronavirus (SARS-COV-2) antibody molecules is realized by utilizing the change of channel MOF material conductivity caused by the specific combination between the protein antigen and the protein antibody. Compared with the reported detection materials, Ni₃(HITP)₂The film has good conductivity, can grow in situ at a channel, is in good contact with a substrate, is uniform, is porous, has a plurality of active sites, and is easy to adsorb virus molecules to be detected, so that the detection sensitivity of the virus molecules is improved to a great extent, and the detection time is shortened.

Unlike field effect transistors that use graphene or silicon nanowires as channel sensitive materials, the present invention uses metal organic framework materials as sensor sensitive materials for the first time to form biosensors capable of detecting novel coronavirus antibody molecules. According to the invention, the source-drain gold electrodes are prepared, then the MOF material is grown in situ by a hydrothermal method (namely, a uniform MOF film can be prepared by using a simple in-situ growth method, the MOF field effect transistor is prepared), then the liquid tank is made by using PDMS, aldehyde groups are introduced by direct glutaraldehyde chemical modification, and the sensor can be prepared by chemically connecting the aldehyde groups with the amino groups of the probe antigen, so that the steps are simple and stable.

2. The invention utilizes Ni₃(HITP)₂Conductive MOF film field effect transistor, preparing device PDMS liquid tank and obtainingMOF-based field effect transistor biosensors. The sensor has good stability, small volume and convenient carrying and transfer.

3. When the biosensor is used for carrying out new corona virus antibody molecules, antigen probe molecules are functionally modified on the surface of the MOF material, and the electrical signals of the sensor are changed through the specific combination of molecules to be detected and the probe molecules, so that the detection of the new corona antibody molecules by the sensor can be realized, particularly the detection of the low-concentration specific new corona antibody molecules, and the detection limit is as low as 10 pg/mL. The biosensor can be matched with the existing semiconductor parameter analyzer for direct detection, and after the solution to be detected of the new coronavirus is added, the change of the current value is directly measured in the liquid tank area to realize detection, so that the biosensor has the advantages of rapid detection and high sensitivity.

In conclusion, the invention provides a new way for the detection of novel coronavirus antibody molecules, and has the great advantages of high detection speed, high sensitivity, simple and convenient operation, easy carrying, real-time detection and the like; the biosensor based on the invention can realize low-concentration sensitive test of novel coronavirus antibody molecules, and the detection limit is as low as 10 pg/mL. The invention can be applied to the rapid and sensitive detection of new coronavirus antibody molecular immunology and has wide application prospect.

Drawings

FIG. 1 shows Ni according to the present invention₃(HITP)₂Schematic structure of field effect transistor biosensor.

FIG. 2 shows Ni prepared in example 1 of the present invention₃(HITP)₂Transfer characteristic curve of field effect transistor biosensor.

FIG. 3 shows Ni prepared in example 1 of the present invention₃(HITP)₂Graph of output characteristics of a field effect transistor biosensor.

FIG. 4 shows Ni prepared in example 1 of the present invention₃(HITP)₂A field effect transistor biosensor is used for detecting 10 pg/mL-1 mu g/mL new coronavirus antibody molecules.

Detailed Description

In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described in further detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention. In addition, the technical features involved in the embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.

Ni on which the following examples are based₃(HITP)₂The preparation method of the field effect transistor comprises the following steps:

step 1, in Si/SiO₂Spin-coating positive photoresist on the surface of a wafer substrate, rotating at 5000rpm for 60 s; pre-baking the substrate coated with the photoresist for 3min on a heating table at 100 ℃; ultraviolet exposure is carried out on the device for 10s under a fixed mask; soaking the exposed substrate into a developing solution for developing for 15 s; after the development is finished, taking the substrate out, drying the substrate by a nitrogen gun, and baking the substrate for 3min on a heating table at 110 ℃; after photoetching, carrying out magnetron sputtering gold plating process on the device, wherein the sputtering vacuum degree is 26mTorr, the sputtering current is 38mA, and the sputtering time is 100 s; and ultrasonically stripping by using acetone after sputtering is finished so as to realize the preparation of the patterned source drain electrode, wherein the ultrasonic time is 15 s.

Step 2, in-situ growth of Ni on the surface of the electrode through low-temperature hydrothermal reaction after preparation of the source electrode and the drain electrode₃(HITP)₂A material. Firstly, weighing 6.6mg of 2,3,6,7,10, 11-hexaamino triphenyl Hexahydrochloride (HATP), fully stirring and dissolving in 5mL of deionized water; 10mg of nickel chloride hexahydrate (NiCl) were weighed₂·6H₂O) fully stirring and dissolving in 5mL of deionized water; 0.3mL of ammonia water (NH) was taken₃·6H₂O) adding the mixture into a nickel chloride hexahydrate solution; then, dropwise adding the mixed solution of ammonia water and nickel chloride into the HATP solution, and stirring for 1 min; inverting the device containing the source and drain electrodes prepared in the step 1 on the surface of the reaction mixed solution, and heating the reaction mixed solution by adopting a water bath to enable the MOF material to grow between the source and drain electrodes in situ, wherein the reaction time is 1h and the reaction temperature is 65 ℃; taking out the device after the reaction is finished, carrying out vacuum drying on the device at the drying temperature of 100 ℃ for 2h, and successfully preparing Ni after the drying is finished₃(HITP)₂A field effect transistor.

By usingNi as above₃(HITP)₂The field effect transistor further forms a biosensor to detect the novel coronavirus, and may include the steps of: in Ni₃(HITP)₂Preparing a PDMS solution liquid tank (the cross-sectional area of the solution liquid tank can be larger than the surface area of the channel area, for example, the channel area can be completely in the solution liquid tank), modifying a glutaraldehyde crosslinking agent to the surface of the channel MOF material through cultivation, and then fixing antigen protein probe molecules to the surface of the MOF material through glutaraldehyde connection through cultivation, thereby obtaining the MOF-based field effect transistor biosensor. By applying fixed grid voltage and source-drain voltage, the change of source-drain end electric signals is measured, thereby realizing the detection of the novel coronavirus antibody molecules.

The method comprises the steps of modifying glutaraldehyde connecting molecules to the surface of a channel MOF material, then modifying antigen protein probe molecules to the surface of the MOF material through glutaraldehyde connection, specifically, dropwise adding a glutaraldehyde solution into a device liquid tank for cultivation at the cultivation temperature of 25 ℃ for 1-2 hours, sucking away the glutaraldehyde solution, dropwise adding a neo-corona antigen molecule solution into the device liquid tank for cultivation at the cultivation temperature of 0-4 ℃, and cultivating for 8-12 hours.

In the detection, for example, the following steps may be performed:

(S1) taking out the cultured MOF-based field effect transistor biosensor from a low-temperature environment, sucking away the antigen probe molecule solution in the liquid tank, adding 15-20 mu L of PBS solution to clean the residual probe molecules in the liquid tank, and standing for 5-10 min to restore the device to a stable state.

(S2) mixing the PBS solution with the pH of 7.4 with the antibody molecules to prepare solutions with different concentrations, wherein the concentration is 10 pg/mL-1 mu g/mL; and (3) dropwise adding casein solution serving as a confining liquid into a sensor liquid groove for incubation at room temperature.

(S3) respectively contacting source and drain end probes of a Keysight B1500A semiconductor testing system with source and drain end electrode press pins of a sensor, and extending a grid end probe into a liquid grid PBS (phosphate buffer solution) solution of a liquid tank of the sensor without contacting MOF (metal organic framework) materials of a channel in the liquid tank.

(S4) fixing the gate voltage to-0.1V, fixing the source-drain voltage to-0.1V,the value of the source-drain current of the sensor, namely the substrate current signal I, is measured when the PBS solution is used as a liquid grid_pbs(ii) a And (2) sequentially dripping a virus antibody solution with small concentration to large concentration into a sensor liquid tank, then sequentially testing the change conditions of electric signals of a source electrode and a drain electrode of a device after the antibody solution with 10pg/mL, 100pg/mL, 1ng/mL,10ng/mL,100ng/mL and 1 mu g/mL is added into the sensor liquid tank, and realizing the rapid and sensitive detection of the novel coronavirus antibody molecule by recognizing the change of the electric signals.

Wherein, the culture of the sealing solution is to suck out the PBS solution in the liquid tank, add 15-20 mul of the sealing solution, namely 5% casein PBS solution, and culture for 1-2 h at room temperature and 25 ℃.

And (3) testing a substrate current signal, namely sucking the sealing liquid from the liquid tank, adding 5-10 mu L of PBS (phosphate buffer solution) solution to clean residual casein molecules in the liquid tank of the sensor, adding 15-20 mu L of PBS solution again, and testing the change condition of a source drain end current signal with time by using a testing system for 180s to obtain I_pbsA substrate current signal.

The detection process of the new coronavirus antibody solution comprises the steps of sucking away the solution in a liquid tank, adding 5-10 mu L of PBS solution to clean a sensor liquid tank, then adding 15-20 mu L of new coronavirus antibody solution, and after incubation for 5-10 min, measuring the change of a current signal at a source drain terminal along with time to obtain a current signal under the antibody concentration.

When detecting the new coronavirus antibody solution, the source-drain voltage and the grid voltage are fixed at-0.1V.

In addition, the above step (S4) can be repeated, the change of the electric signals generated by the antibody solution under the concentration of 10pg/mL, 100pg/mL, 1ng/mL,10ng/mL,100ng/mL and 1 μ g/mL is tested in sequence, and the sensitive detection of the new coronavirus antibody molecule is realized by recognizing different current signals under different concentrations.

The following are specific examples:

example 1:

ni₃(HITP)₂A field effect transistor biosensor and a method for preparing the same, comprising the steps of:

step 1, based on Ni₃(HITP)₂Field effect crystalA tube, which uses Polydimethylsiloxane (PDMS) to prepare a cylindrical fluid bath in a channel area, and the cross section of the fluid bath has an inner diameter of 3mm and a height of 1 mm; and curing at 25 ℃ to form a PDMS liquid tank for storing the solution to be detected.

Step 2, dripping 15 mu L of glutaraldehyde solution with the mass concentration of 0.1% into a liquid tank of the device for cultivation, wherein the cultivation temperature is 25 ℃, and the cultivation time is 1 h; sucking away glutaraldehyde solution after the incubation is finished, taking 15 mu L of neocoronal antigen molecule solution (SRAS-COV-2N protein, 0588-V07E, Nano Biological Inc.) with the concentration of 100 mu g/mL, and dropwise adding the neocoronal antigen molecule solution into a device liquid tank for incubation at the incubation temperature of about 0 ℃ for 8 hours; obtaining Ni after the cultivation₃(HITP)₂A field effect transistor biosensor has a device structure as shown in FIG. 1.

And 3, taking the prepared field effect transistor biosensor out of the low-temperature environment, sucking away the antigen probe molecule solution in the liquid tank, adding 20 mu L of PBS (phosphate buffer solution) solution to clean residual probe molecules in the liquid tank, and standing for 10min to restore the device to a stable state.

Step 4, adopting a Keysight B1500A semiconductor test system to test Ni₃(HITP)₂And (3) testing the electrical property of the field effect transistor biosensor. And respectively contacting the source drain end probe of the test system with the source drain end electrode pressing pin of the sensor, and extending the grid end probe into a PBS (phosphate buffer solution) solution of a liquid grid of a liquid tank of the sensor without contacting the MOF material of a channel in the liquid tank. Setting parameters to test the transfer output characteristics of the device: setting a fixed source-drain voltage of-0.1V, and testing the source-drain current change under the scanning grid voltage of-1.5-1V to obtain a device transfer characteristic curve as shown in figure 2; setting the interval gate voltages of-0.1V, -0.05V, 0V, 0.05V and 0.1V, and testing the source leakage current change under the scanning source-drain voltage of 0-0.2V to obtain a device output characteristic curve as shown in figure 3; the result shows that the transfer curve shows the P-type hole multi-photon conduction characteristic of the device, and the output characteristic curve represents the good modulation effect of the device under the gate voltage of-0.1V.

Step 5, mixing phosphate buffer solution (PBS solution) with the pH of 7.4 with antibody molecules (SRAS-COV-2N protein antibody, 40588-R00004, Sino Biological Inc.) to prepare solutions with different concentrations, wherein the concentrations are 10 pg/mL-1 mug/mL; 20 mu.L of 5% casein solution is taken as a confining liquid and dripped into a sensor liquid groove to be incubated for 1h at room temperature.

Step 6, sucking the sealing liquid from the liquid tank, then adding 5 mu L of PBS (phosphate buffer solution) solution to clean the residual casein molecules in the liquid tank of the sensor, adding 20 mu L of PBS solution again, and standing and culturing for 10 min; setting the grid voltage of a test system to-0.1V, fixing the source-drain voltage to-0.1V, and testing the source-drain current value of the sensor in the PBS solution, namely a substrate current signal I_pbs(ii) a Adding 20 μ L of new coronavirus antibody solution with concentration of 10pg/mL, and testing the change of the current signal at the source and drain terminals with time after 10min incubation to obtain the current signal at the concentration of 10 pg/mL. After the concentration test is finished, 5 mu L of PBS solution is added to clean a sensor liquid tank, the test steps are repeated, 20 mu L of 100pg/mL, 1ng/mL,10ng/mL,100ng/mL and 1 mu g/mL antibody solutions are sequentially added from low concentration to high concentration, the change condition of the electric signals of the source and drain terminals of the device is tested, the quick and sensitive detection on the novel coronavirus antibody molecules is realized by recognizing the change of the electric signals, and the antibody concentration test result is shown in figure 4. The result shows that the sensor can realize rapid and sensitive detection on the antibody molecules of the new coronavirus, and the detection limit is as low as 10 pg/mL.

Example 2:

ni₃(HITP)₂A field effect transistor biosensor and a method for preparing the same, comprising the steps of:

step 1, based on Ni₃(HITP)₂A field effect transistor, wherein a cylindrical liquid groove is prepared in a channel region by using Polydimethylsiloxane (PDMS), and the cross section of the cylindrical liquid groove has the inner diameter of 4mm and the height of 1.5 mm; curing at 25 ℃ to form a PDMS liquid tank for storing the solution to be detected.

Step 2, dripping 25 mu L of glutaraldehyde solution with the mass concentration of 0.5% into a liquid tank of the device for cultivation, wherein the cultivation temperature is 25 ℃, and the cultivation time is 2 hours; after the cultivation is finished, sucking away the glutaraldehyde solution, dropwise adding 25 mu L of the new crown antigen molecule solution with the concentration of 200 mu g/mL into a liquid tank of the device for cultivation, wherein the cultivation temperature is about 0 ℃, and the cultivation time is 12 hours; obtaining Ni after the cultivation₃(HITP)₂A field effect transistor biosensor.

And 3, taking the prepared field effect transistor biosensor out of the low-temperature environment, sucking away the antigen probe molecule solution in the liquid tank, adding 20 mu L of PBS (phosphate buffer solution) solution to clean residual probe molecules in the liquid tank, and standing for 10min to restore the device to a stable state.

Step 4, adopting a Keysight B1500A semiconductor test system and using Ni₃(HITP)₂And (3) detecting the concentration of the antibody molecules of the new coronavirus by using a field effect transistor biosensor. And respectively contacting the source drain end probe of the test system with the source drain end electrode pressing pin of the sensor, and extending the grid end probe into a PBS (phosphate buffer solution) solution of a liquid grid of a liquid tank of the sensor without contacting the MOF material of a channel in the liquid tank.

Step 5, mixing the PBS solution and the antibody molecules to prepare solutions with different concentrations, wherein the concentration is 10 pg/mL-1 mu g/mL; 15 mu.L of 5% casein solution is taken as a confining liquid and dripped into a sensor liquid groove to be incubated for 1h at room temperature.

Step 6, sucking the sealing liquid from the liquid tank, then adding 5 mu L PBS solution to clean the residual casein molecules in the liquid tank of the sensor, adding 15 mu L PBS solution again, and standing and culturing for 10 min; setting the grid voltage of a test system to-0.1V, fixing the source-drain voltage to-0.1V, and testing the source-drain current value of the sensor in the PBS solution, namely a substrate current signal I_pbs(ii) a Adding 15 μ L of new coronavirus antibody solution with concentration of 10pg/mL, and testing the change of the current signal at the source and drain terminals with time after 10min incubation to obtain the current signal at the concentration of 10 pg/mL. After the concentration test is finished, 5 mu L of PBS solution is added to clean a sensor liquid tank, the test steps are repeated, 15 mu L of 100pg/mL, 1ng/mL,10ng/mL,100ng/mL and 1 mu g/mL antibody solutions are sequentially added from low concentration to high concentration, the change condition of the electric signals of the source and drain terminals of the device is tested, and the quick and sensitive detection on the novel coronavirus antibody molecules is realized by recognizing the change of the electric signals.

Since the invention is based on existing Ni₃(HITP)₂On the basis of the conductive MOF film field effect transistor, Ni is obtained by preparing a PDMS solution liquid tank and modifying and fixing probe molecules through a glutaraldehyde cross-linking agent₃(HITP)₂A field effect transistor biosensor; then, byThe specific combination of the molecules to be detected and the probe molecules changes the electrical signals of the sensor, thereby realizing the rapid and sensitive detection of the sensor on the novel coronavirus antibody molecules; with respect to Ni-based₃(HITP)₂Conductive MOF thin film field effect transistors, otherwise not specified, can be referred to in the art (CN 110429032A).

It will be understood by those skilled in the art that the foregoing is only a preferred embodiment of the present invention, and is not intended to limit the invention, and that any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the scope of the present invention.