Biosensor, test kit and test device

Abstract

The present application relates to a biosensor, a test kit and a test device. The biosensor comprises: a substrate; a channel layer; a source electrode; a drain electrode; a dielectric layer; a gate electrode, which has an extension end; and a biological probe, which is fixed on the surface of the extension end that is away from the dielectric layer. The biosensor has a relatively high test speed and is easy to operate when testing a target test object.

Description

Biosensors, test kits, and testing equipment

[0001] This application claims priority to the Chinese patent application filed with the China Patent Office on July 26, 2023, with application number 202310921361.9 and invention name “Biosensor, Detection Kit and Detection Equipment”, the entire contents of which are incorporated by reference into this application. Technical Field

[0002] The present application relates to the field of sensor technology, and in particular to a biosensor, a detection kit, and a detection device. Background Art

[0003] Virus classification and detection have found widespread application in fields such as biology and medicine. Currently, these methods primarily rely on conventional polymerase chain reaction (PCR) or fluorescent quantitative PCR. These methods require long detection times and high requirements for instrument operation and laboratory environment. Therefore, there is a need for a method that can rapidly classify and easily detect target viruses.

[0004] Summary of the Invention

[0005] Based on this, it is necessary to provide a biosensor, a detection kit, and a detection device. When the biosensor detects a target object, the detection speed is fast and the operation is simple.

[0006] In a first aspect, the present application provides a biosensor, comprising:

[0007] substrate;

[0008] a channel layer, the channel layer being located on the surface of the substrate;

[0009] a source electrode and a drain electrode, wherein the source electrode and the drain electrode are alternately and spaced apart from each other on a surface of the channel layer away from the substrate;

[0010] a dielectric layer, the dielectric layer covering a surface of the channel layer on which the source electrode and the drain electrode are not provided, and a surface of the source electrode and the drain electrode away from the substrate;

[0011] a gate electrode, wherein the gate electrodes are multiple in number and are located on a surface of the dielectric layer away from the channel layer; the multiple gate electrodes are spaced apart from the source electrode and the drain electrode and are located between the source electrode and the drain electrode; the gate electrode has an extended end, and the extended end protrudes from the source electrode, the drain electrode, the channel layer, and the dielectric layer in the length direction of the gate electrode;

[0012] A biological probe is fixed on the surface of the extended end away from the dielectric layer.

[0013] In some embodiments, the gate electrode further has a connecting portion, the connecting portion is detachably connected to the extended end, and the biological probe is fixed on a surface of the connecting portion.

[0014] In some embodiments, the biosensor further includes a sample slot for receiving a sample to be tested, the sample slot is disposed on the surface of the medium layer, and the connecting portion is located in the sample slot.

[0015] In some embodiments, each of the extended ends is fixed with the biological probe capable of specifically binding to a different target detection substance.

[0016] In some embodiments, the dielectric layer covers the surface of the substrate not provided with the channel layer.

[0017] In some embodiments, a surface of the gate electrode close to the substrate is flush with a surface of the dielectric layer away from the substrate.

[0018] In some embodiments, the biological probe comprises at least one of an antibody, an antigen, an enzyme, RNA, PNA, a single-stranded DNA, a double-stranded DNA, a two-dimensional DNA nanostructure, and a three-dimensional DNA nanostructure.

[0019] In some embodiments, the material of the channel layer includes at least one of graphene, transition metal dichalcogenide, silicon, oxide semiconductor, and polymer semiconductor.

[0020] In some embodiments, the material of the dielectric layer includes at least one of zirconium oxide and hafnium oxide.

[0021] In some embodiments, the substrate includes one of glass, silicon dioxide, sapphire, and mica.

[0022] In some embodiments, the materials of the source electrode, the drain electrode, and the gate electrode are each independently selected from at least one of gold, silver, copper, titanium, chromium, a carbon material, and a conductive polymer material.

[0023] In some embodiments, the thickness of the source electrode, the drain electrode, and the gate electrode are each independently selected from 20 nm to 500 nm.

[0024] In a second aspect, the present application provides a detection kit comprising: a biosensor as described in any one of the above items.

[0025] In a third aspect, the present application provides a detection device, comprising: any of the above-mentioned biosensors or the above-mentioned detection kits.

[0026] The biosensor comprises a substrate, a channel layer, a source electrode, a drain electrode, a dielectric layer, a gate electrode, and a bioprobe. The gate electrodes are multiple and have extended ends, with the bioprobes affixed to the surface of each extended end away from the dielectric layer. The biosensor is based on a field-effect transistor and has multiple channels, with the bioprobes affixed to the surfaces of the extended ends. When using the biosensor to detect a target substance, a specific bioprobe can be affixed to the surface of the extended end. When a sample to be tested is dripped onto the area on the gate electrode surface where the bioprobe is affixed, if the sample contains a target substance that can be specifically recognized by the bioprobe, the bioprobe will specifically bind to the target substance, and the electrical signal between the source and drain electrodes will be monitored. If the bioprobe specifically binds to the target substance, the electrical signal will immediately and significantly change when specific binding occurs. If no specific binding occurs, the electrical signal will not change significantly. When using this biosensor to detect a target substance, the detection speed is fast and the operation is simple. Furthermore, the multi-channel transistor can be used to affix multiple different probes to the multiple gate electrodes, allowing for simultaneous detection of different target substances. Furthermore, the gate electrode has an extended end. When adding samples, the sample to be tested only needs to be added to the area on the extended end where the probe is attached, thereby reducing the risk of contamination of the source electrode, drain electrode and channel. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] FIG1 is a schematic diagram of a partial structure of a biosensor provided in one embodiment of the present application;

[0028] FIG2 is a schematic structural diagram of a biosensor provided in one embodiment of the present application;

[0029] FIG3 is a schematic structural diagram of a biosensor provided in another embodiment of the present application;

[0030] FIG4 is a schematic diagram of the detection results of the novel coronavirus provided in Example 1 of the present application;

[0031] FIG5 is a schematic diagram of the detection results of influenza A virus provided in Example 1 of the present application;

[0032] FIG6 is a schematic diagram of the influenza B virus detection results provided in Example 1 of the present application.

[0033] DESCRIPTION OF REFERENCE NUMERALS 100 , substrate; 200 , channel layer; 300 , drain electrode; 400 , source electrode; 500 , dielectric layer; 600 , gate electrode; 620 , extension end; 630 , connection portion; 700 , biological probe DETAILED DESCRIPTION

[0034] To make the above-mentioned objects, features, and advantages of the present application more clearly understood, the specific embodiments of the present application are described in detail below with reference to the accompanying drawings. The following description sets forth many specific details to facilitate a full understanding of the present application. However, the present application can be implemented in many other ways than those described herein, and those skilled in the art can make similar improvements without violating the scope of the present application. Therefore, the present application is not limited to the specific embodiments disclosed below.

[0035] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this application pertains. The terms used herein in the specification of this application are for the purpose of describing specific embodiments only and are not intended to limit this application. The term "and / or" as used herein includes any and all combinations of one or more of the associated listed items.

[0036] Referring to Figures 1 and 2, the direction indicated by the arrow is the length direction of the gate electrode 600. It can be understood that Figure 2 is a top view of the biosensor. Since the dielectric layer 500 covers the surface of the channel layer 200 where the source electrode 400 and the drain electrode 300 are not provided, as well as the surface of the source electrode 400 and the drain electrode 300 away from the substrate 100, the channel layer 200 is blocked by the dielectric layer 500 in the top view. An embodiment of the present application provides a biosensor, comprising: a substrate 100; a channel layer 200, the channel layer 200 is located on the surface of the substrate 100; a source electrode 400, a drain electrode 300, the source electrode 400 and the drain electrode 300 are alternately arranged on the surface of the channel layer 200 away from the substrate 100; a dielectric layer 500, the dielectric layer 500 covers the surface of the channel layer 200 where the source electrode 400 and the drain electrode 300 are not provided, as well as the surface of the source electrode 400 and the drain electrode 300 away from the substrate 100; a gate electrode 600, the gate electrode 60 0 is multiple, the gate electrode 600 is located on the surface of the dielectric layer 500 away from the channel layer 200; the multiple gate electrodes 600 are spaced apart from the source electrode 400 and the drain electrode 300, and are located between the source electrode 400 and the drain electrode 300, the gate electrode 600 has an extended end 620, and in the length direction of the gate electrode 600, the extended end 620 protrudes from the source electrode 400, the drain electrode 300, the channel layer 200 and the dielectric layer 500; the biological probe 700, the biological probe 700 is fixed on the surface of the gate electrode 600 away from the dielectric layer 500.

[0037] The biosensor comprises a substrate 100, a channel layer 200, a source electrode 400, a drain electrode 300, a dielectric layer 500, a gate electrode 600, and a bioprobe 700. The gate electrodes 600 are multiple and have extended ends 620. The bioprobes 700 are affixed to the surface of each extended end 620, away from the dielectric layer 500. The biosensor is based on a field-effect transistor and has multiple channels. The bioprobes 700 are affixed to the surface of the gate electrode 600. When using the biosensor to detect a target object, a specific bioprobe 700 can be affixed to the surface of the extended end 620. When a sample is dripped onto the surface of the gate electrode 600 where the bioprobe 700 is affixed, if the sample contains a target substance that can be specifically recognized by the bioprobe 700, the bioprobe 700 will specifically bind to the target substance, and the electrical signal between the source electrode 400 and the drain electrode 300 will be monitored. If the bioprobe 700 specifically binds to the target substance, the electrical signal will immediately and significantly change when the specific binding occurs, resulting in a faster detection speed. If no specific binding occurs, the electrical signal will not change significantly. When using this biosensor to detect target substances, the detection speed is fast, the operation is simple, and the specificity is high. Furthermore, the multi-channel transistor can be used to affix multiple different bioprobes 700 to multiple gate electrodes 600, allowing for simultaneous detection of different target substances. The gate electrode 600 has an extended end 620. When adding the sample, the sample only needs to be added to the area of ​​the extended end where the probe is attached. This reduces the risk of contamination of the source electrode, drain electrode, and channel, improves the utilization rate of the biosensor, and enables reuse of the biosensor.

[0038] It is understandable that the biological probe 700 can specifically bind to target detection objects such as nucleic acid biomarkers of viruses, bacteria, fungi, and chlamydia, antibodies, antigens, metabolic small molecules or ions.

[0039] It is understood that the biological probes 700 immobilized on the surface of the gate electrode 600 may be one or more types. Multiple biological probes 700 refer to biological probes 700 that can specifically identify different target analytes. When the biological probes 700 on the surface of the gate electrode 600 are of one type, a single target analyte can be identified and detected. When multiple types of biological probes 700 are immobilized on the surface of the gate electrode 600, the presence of multiple corresponding target analytes in the sample to be tested can also be detected simultaneously.

[0040] For example, when the target detection object is a single-stranded DNA, the biological probe can be a single-stranded DNA complementary thereto. When the target detection object is a bacterium or virus, the biological probe can be an antibody against the bacterium or virus. When the target detection object is an antibody, the biological probe can be a secondary antibody that can specifically recognize the antibody.

[0041] Compared with traditional detection platforms, the biosensor of the present application constructs a field effect transistor biosensor that can detect target detection objects, and can detect multiple target detection objects at the same time. By modifying and fixing multiple biological probes 700 on the gate electrode 600, the complementary hybridization of the nucleic acid molecule base sequence between the biological probe 700 and the corresponding target detection object causes the change in the conductivity of the device to detect multiple target detection objects. It has the advantages of high stability, high integration, simple operation, high sensitivity, short response time, high throughput, and low cost. The present application can solve the problems of long detection time and complex operation of ordinary polymerase chain reaction or fluorescent quantitative polymerase chain reaction, and can overcome the defects of directly fixing the modified biological probe 700 on the semiconductor channel surface in the liquid gate field effect transistor. The biosensor in the present application has a low risk of contamination to the sensor body when in use and can be reused.

[0042] In some embodiments, the gate electrode 600 further includes a connecting portion 630, which is detachably connected to the extension end 620, and the biological probe 700 is fixed to the surface of the connecting portion 630. By providing a detachable connecting portion 630, when using the biosensor for detection, only the sample to be tested is added to the connecting portion 630 for detection, thereby reducing contamination of other components of the biosensor. At the same time, after the detection is completed, the connecting portion 630 can be easily replaced, enabling the reuse of the biosensor. Furthermore, by replacing the connecting portion 630 with different biological probes 700, different target detection objects can be detected.

[0043] In one embodiment, the connecting portion 630 is a detection sheet with the biological probe 700 attached thereto, and the detection sheet is connected to the extension section 620 via a wire point.

[0044] In some embodiments, the biosensor further includes a sample well for receiving a sample to be tested. The sample well is disposed on the surface of the dielectric layer 500, and the connector 630 is located within the sample well. The sample well can limit the location where the sample to be tested can be added. Positioning the sample well so that the connector 630 is located within the sample well allows the sample to be tested to contact and be detected only with the connector 630, thereby reducing contamination of the sample to other components of the biosensor. The biosensor can be reused by simply replacing the connector 630.

[0045] In some embodiments, the sample reservoir is a liquid reservoir or a microfluidic channel.

[0046] Referring to Figure 3 , in some embodiments, a dielectric layer 500 covers the surface of the substrate 100 not provided with the channel layer 200. It will be appreciated that Figure 3 is a top view of the biosensor. Because the dielectric layer 500 covers the surface of the substrate 100 not provided with the channel layer 200, the lower layers in the top view are obscured by the dielectric layer 500. The dielectric layer completely covers the lower layers, further reducing the risk of contamination of the lower layers during sample loading.

[0047] In some embodiments, a surface of the gate electrode 600 close to the substrate 100 is flush with a surface of the dielectric layer 500 away from the substrate 100 .

[0048] In some embodiments, the bioprobe 700 includes at least one of an antibody, an antigen, an enzyme, RNA, PNA, a single-stranded DNA, a double-stranded DNA, a two-dimensional DNA nanostructure, and a three-dimensional DNA nanostructure. It is understood that a DNA nanostructure is an artificial DNA structure that is artificially designed and produces a useful nucleic acid structure.

[0049] In some embodiments, the bio-probe 700 is immobilized on the surface of the gate electrode 600 by at least one of a covalent bonding method, an adsorption method, an embedding method, and a cross-linking method.

[0050] Covalent bonding is one method for modifying electrode surfaces. First, the base electrode surface is pretreated to introduce bonding groups. The desired functional groups are then attached to the electrode surface through chemical bonding organic synthesis reactions. These modified electrodes exhibit numerous excellent properties, such as selective molecular recognition, selective response, and high stability. This modification method allows chemical modifiers with different desired functional groups to be covalently bonded to different pretreated electrode surfaces.

[0051] The adsorption method is a method that uses the non-covalent bond between the base electrode and the modifier to fix the modifier on the surface of the solid base electrode to form a film.

[0052] The principle of the encapsulation method is to trap biomolecules within the porous network of a water-insoluble gel polymer. The encapsulation method is simple to operate, has minimal impact on the activity of the biomolecules, and produces immobilized biomolecules with high strength.

[0053] Cross-linking involves the use of bifunctional or multifunctional reagents to directly cross-link with reactive groups on the biomolecule's surface, such as amino or carboxyl groups, forming covalent bonds to immobilize the biomolecule. This method results in a tight bond between the biomolecule and the carrier. Commonly used cross-linking agents include glutaraldehyde, toluene diisocyanate, and bis(azobiphenyl).

[0054] In some embodiments, the material of the channel layer 200 includes at least one of graphene, transition metal dichalcogenides, silicon, oxide semiconductors, and polymer semiconductors. Transition metal dichalcogenides refer to compounds containing transition metal elements and sulfur elements. Optionally, the transition metal dichalcogenides include at least one of molybdenum disulfide and tungsten disulfide.

[0055] In some embodiments, the material of the dielectric layer 500 includes at least one of zirconium oxide and hafnium oxide, both of which are dielectric materials with high dielectric constants.

[0056] In some embodiments, the substrate 100 includes one of glass, silicon dioxide, sapphire, and mica.

[0057] In some embodiments, the material of the source electrode 400 includes at least one of gold, silver, copper, titanium, chromium, a carbon material, and a conductive polymer material.

[0058] In some embodiments, the material of the drain electrode 300 includes at least one of gold, silver, copper, titanium, chromium, a carbon material, and a conductive polymer material.

[0059] In some embodiments, the material of the gate electrode 600 includes at least one of gold, silver, copper, titanium, chromium, a carbon material, and a conductive polymer material.

[0060] In some embodiments, the thickness of the source electrode 400 is 20 nm to 500 nm. Alternatively, the thickness of the source electrode 400 is 20 nm, 30 nm, 40 nm, 50 nm, 60 nm, 70 nm, 80 nm, 90 nm, 100 nm, 110 nm, 120 nm, 130 nm, 140 nm, 150 nm, 160 nm, 170 nm, 180 nm, 190 nm, 200 nm, 210 nm, 220 nm, 230 nm, 240 nm, 250 nm, 260nm, 270nm, 280nm, 290nm, 300nm, 310nm, 320nm, 330nm, 340nm, 350nm, 360nm, 370nm, 380nm, 390nm, 400nm, 410nm, 420nm, 430nm, 440nm, 450nm, 460nm, 470nm, 480nm, 490nm or 500nm.

[0061] In some embodiments, the thickness of the drain electrode 300 is 20 nm to 500 nm. Alternatively, the thickness of the drain electrode 300 is 20 nm, 30 nm, 40 nm, 50 nm, 60 nm, 70 nm, 80 nm, 90 nm, 100 nm, 110 nm, 120 nm, 130 nm, 140 nm, 150 nm, 160 nm, 170 nm, 180 nm, 190 nm, 200 nm, 210 nm, 220 nm, 230 nm, 240 nm, 250 nm, 260nm, 270nm, 280nm, 290nm, 300nm, 310nm, 320nm, 330nm, 340nm, 350nm, 360nm, 370nm, 380nm, 390nm, 400nm, 410nm, 420nm, 430nm, 440nm, 450nm, 460nm, 470nm, 480nm, 490nm or 500nm.

[0062] In some embodiments, the thickness of the gate electrode 600 is 20 nm to 500 nm. Alternatively, the thickness of the gate electrode 600 is 20 nm, 30 nm, 40 nm, 50 nm, 60 nm, 70 nm, 80 nm, 90 nm, 100 nm, 110 nm, 120 nm, 130 nm, 140 nm, 150 nm, 160 nm, 170 nm, 180 nm, 190 nm, 200 nm, 210 nm, 220 nm, 230 nm, 240 nm, 250 nm, 260nm, 270nm, 280nm, 290nm, 300nm, 310nm, 320nm, 330nm, 340nm, 350nm, 360nm, 370nm, 380nm, 390nm, 400nm, 410nm, 420nm, 430nm, 440nm, 450nm, 460nm, 470nm, 480nm, 490nm or 500nm.

[0063] Another embodiment of the present application provides a method for preparing a biosensor, comprising:

[0064] forming a channel layer 200 on a substrate 100;

[0065] A source electrode 400 and a drain electrode 300 are formed on the surface of the channel layer 200 , and the source electrode 400 and the drain electrode 300 are alternately arranged;

[0066] A dielectric layer 500 is formed on the surface of the channel layer 200 , and the dielectric layer 500 covers the surface of the channel layer 200 where the source electrode 400 and the drain electrode 300 are not formed, as well as the surface where the source electrode 400 and the drain electrode 300 are formed.

[0067] A gate electrode 600 is formed on the surface of the dielectric layer 500. The gate electrodes 600 are multiple and are located on the surface of the dielectric layer 500. The multiple gate electrodes 600 are spaced apart from the source electrode 400 and the drain electrode 300 and are located between the source electrode 400 and the drain electrode 300. The gate electrode 600 has an extended end 620. In the length direction of the gate electrode 600, the extended end 620 protrudes from the source electrode 400, the drain electrode 300, the channel layer 200, and the dielectric layer 500.

[0068] The bio-probe 700 is fixed on the surface of the gate electrode 600 away from the dielectric layer 500 .

[0069] In some embodiments, a method for preparing a biosensor comprises:

[0070] (1) The channel layer 200 is formed on the substrate 100 .

[0071] (2) The positions of the patterned source electrode 400 and the drain electrode 300 are defined on the surface of the channel layer 200 by photolithography, and the source electrode 400 and the drain electrode 300 are then deposited. The source electrode 400 and the drain electrode 300 are alternately arranged. The materials of the source electrode 400 and the drain electrode 300 are independently selected from at least one of gold, silver, copper, titanium, chromium, carbon materials and conductive polymer materials. The thickness of the source electrode and the drain electrode are independently selected from 20 nm to 500 nm.

[0072] (3) A dielectric layer 500 is deposited on the surface of the channel layer 200. The dielectric layer 500 covers the entire surface of the channel layer 200 where the source electrode 400 and the drain electrode 300 are not provided, as well as the surface of the source electrode 400 and the drain electrode 300. The material of the dielectric layer 500 includes at least one of zirconium oxide and hafnium oxide.

[0073] (4) Using photolithography, the position of the patterned gate electrode 600 is defined on the surface of the dielectric layer 500, and then the gate electrode 600 is deposited. The number of gate electrodes 600 is multiple, and the gate electrodes 600 are located on the surface of the dielectric layer 500; the multiple gate electrodes 600 are spaced apart from the source electrode 400 and the drain electrode 300, and are located between the source electrode 400 and the drain electrode 300. The material of the gate electrode 600 is selected from at least one of gold, silver, copper, titanium, chromium, carbon material and conductive polymer material, and the thickness of the gate electrode 600 is 20nm to 500nm; the gate electrode 600 has an extended end 620, and in the length direction of the gate electrode 600, the extended end 620 protrudes from the source electrode 400, the drain electrode 300, the channel layer 200 and the dielectric layer 500. The gate electrode 600 also has a connecting portion 630, and the connecting portion 630 is detachably connected to the extended end 620.

[0074] (5) The bioprobe 700 is fixed on the surface of the connection portion 630 of the gate electrode 600 away from the dielectric layer 500 .

[0075] In one embodiment, the biosensor is prepared by the following steps:

[0076] (1) The channel layer 200 is formed on the substrate 100 .

[0077] (2) The positions of the patterned source electrode 400 and the drain electrode 300 are defined on the surface of the channel layer 200 by photolithography, and the source electrode 400 and the drain electrode 300 are then deposited. The source electrode 400 and the drain electrode 300 are alternately arranged. The materials of the source electrode 400 and the drain electrode 300 are independently selected from at least one of gold, silver, copper, titanium, chromium, carbon materials and conductive polymer materials. The thickness of the source electrode and the drain electrode are independently selected from 20 nm to 500 nm.

[0078] (3) A dielectric layer 500 is deposited on the surface of the channel layer 200. The dielectric layer 500 covers the entire surface of the channel layer 200 where the source electrode 400 and the drain electrode 300 are not provided, as well as the surface of the source electrode 400 and the drain electrode 300. The material of the dielectric layer 500 includes at least one of zirconium oxide and hafnium oxide.

[0079] (4) Using photolithography, the position of the patterned gate electrode 600 is defined on the surface of the dielectric layer 500, and then the gate electrode 600 is deposited. The number of gate electrodes 600 is multiple, and the gate electrodes 600 are located on the surface of the dielectric layer 500; the multiple gate electrodes 600 are spaced apart from the source electrode 400 and the drain electrode 300, and are located between the source electrode 400 and the drain electrode 300. The material of the gate electrode 600 is selected from at least one of gold, silver, copper, titanium, chromium, carbon material and conductive polymer material, and the thickness of the gate electrode 600 is 20nm to 500nm; the gate electrode 600 has an extended end 620, and in the length direction of the gate electrode 600, the extended end 620 protrudes from the source electrode 400, the drain electrode 300, the channel layer 200 and the dielectric layer 500. The gate electrode 600 also has a connecting portion 630, and the connecting portion 630 is detachably connected to the extended end 620.

[0080] (5) The bioprobe 700 is fixed on the surface of the connection portion 630 of the gate electrode 600 away from the dielectric layer 500 .

[0081] Yet another embodiment of the present application provides a detection kit, comprising: any one of the above-mentioned biosensors.

[0082] Yet another embodiment of the present application provides a detection device, comprising: any of the above-mentioned biosensors or the above-mentioned detection kit.

[0083] The following is a specific implementation method

[0084] Example 1

[0085] biosensors

[0086] 1 to 3 , the biosensor in this embodiment has the following structure: a substrate 100; a channel layer 200, the channel layer 200 being located on the surface of the substrate 100; a source electrode 400 and a drain electrode 300, the source electrodes 400 and the drain electrodes 300 being alternately spaced apart on the surface of the channel layer 200 away from the substrate 100; a dielectric layer 500, the dielectric layer 500 covering the surface of the channel layer 200 not provided with the source electrode 400 and the drain electrode 300, and covering the surface of the substrate 100 not provided with the channel 200; and a plurality of gate electrodes 600, the plurality of gate electrodes 600 being located on the surface of the dielectric layer 500 away from the channel layer 200 and alternately spaced apart with the source electrodes 400 and the drain electrodes 300. The gate electrodes 600 are located between the source electrodes 400 and the drain electrodes 300, and the surfaces of the gate electrodes 600 close to the substrate 100 are flush with the surface of the dielectric layer 500 away from the substrate 100. The gate electrode 600 has an extended end 620 that protrudes from the source electrode 400, the drain electrode 300, the channel layer 200, and the dielectric layer 500 along its length. The gate electrode 600 also has a connecting portion 630 that is detachably connected to the extended end 620. Three types of biological probes 700 are fixed to the surface of the connecting portion 630. The biological probes 700 are fixed to the surface of the gate electrode 600 that is away from the dielectric layer 500. In the present application, the substrate 100 is a silicon substrate 100 having a silicon dioxide layer on the surface, the channel layer 200 is made of a single-layer graphene film, the dielectric layer 500 is made of zirconium oxide, the source electrode 400 and the drain electrode 300 are both 5nm chromium-40nm gold composite electrodes, the gate electrode is a 40nm gold electrode, and there are three types of biological probes 700, three of which are modified with thiol groups at the ends. These three biological probes 700 can be connected to the nucleic acid molecules of three target detection objects, including the new coronavirus, influenza A virus, and influenza B virus, respectively, through the principle of base complementarity. A sample slot is also included, and the sample slot is arranged on the surface of the connecting portion 630.

[0087] Preparation of biosensors

[0088] (1) A single-layer graphene film is prepared on a copper foil by chemical vapor deposition, and the prepared graphene film is transferred to a clean silicon dioxide / silicon substrate 100 by electrochemical stripping.

[0089] (2) The patterned source electrode 400 and drain electrode 300 are defined by ultraviolet light lithography and oxygen ion etching technology, and then a 5 nm chromium-40 nm gold composite electrode is prepared as the source electrode 400 and drain electrode 300 by thermal evaporation.

[0090] (3) Zirconium oxide is deposited on the surface of the graphene film as a dielectric layer 500 . The dielectric layer 500 covers the surface of the channel layer 200 where the source electrode 400 and the drain electrode 300 are not provided, as well as the surface where the source electrode 400 and the drain electrode 300 are provided.

[0091] (4) A patterned gate electrode 600 is deposited on the surface of the dielectric layer 500. The gate electrode 600 is a gold electrode with a thickness of 40 nm. The gate electrode 600 has an extended end 620. In the length direction of the gate electrode 600, the extended end 620 protrudes from the source electrode 400, the drain electrode 300, the channel layer 200 and the dielectric layer 500. The gate electrode 600 also has a connecting portion 630, which is detachably connected to the extended end 620.

[0092] (5) The surfaces of the connecting portions 630 of three different gate electrodes 600 were contacted with three solutions containing three biological probes 700 that can specifically bind to the new coronavirus, influenza A virus, and influenza B virus, respectively, for 10 minutes each time. After each contact, the gate electrode 600 was rinsed with ultrapure water. The three biological probes 700 were fixedly connected to the surface of the connecting portion 630 of the gate electrode 600 through a gold-thiol covalent bond.

[0093] Target object detection

[0094] An upper respiratory tract swab sample containing the novel coronavirus (COVID-19) but free of influenza A and B viruses was processed to extract viral nucleic acid. The process involved extracting 200 microliters of sample from the collection tube of the upper respiratory tract swab sample and placing it in a nucleic acid extraction kit to obtain a solution containing COVID-19 nucleic acid molecules. This solution was then dripped onto the surface of the connector 630 in the sample well, and the current between the source electrode 400 and the drain electrode 300 was measured.

[0095] 4 to 6 , when a biosensor fixed with three biological probes 700 for detecting the novel coronavirus, influenza A virus, and influenza B virus is used to detect a sample containing the novel coronavirus but not influenza A virus and influenza B virus, it can be seen that the gate electrode 600 fixed with the novel coronavirus detection probe combines with the novel coronavirus in the sample, resulting in a significant change in the electrical signal between the source electrode 400 and the drain electrode 300, while the other two electrical signals do not undergo significant changes.

[0096] The technical features of the above-mentioned embodiments can be combined arbitrarily. In order to make the description concise, not all possible combinations of the technical features in the above-mentioned embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0097] The above-described embodiments merely represent several implementation methods of the present application. While the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the patent. It should be noted that a person skilled in the art could make several modifications and improvements without departing from the spirit of the present application, all of which fall within the scope of protection of the present application. Therefore, the scope of protection of the patent in this application shall be based on the appended claims, and the specification and drawings may be used to interpret the claims.

Claims

1. A biosensor comprising: substrate; a channel layer, the channel layer being located on a surface of the substrate; A source electrode and a drain electrode, wherein the source electrode and the drain electrode are alternately arranged at intervals on a surface of the channel layer away from the substrate; a dielectric layer, the dielectric layer covering a surface of the channel layer where the source electrode and the drain electrode are not provided, and a surface of the source electrode and the drain electrode away from the substrate; A gate electrode, wherein the number of the gate electrodes is plural and the gate electrodes are located on a surface of the dielectric layer away from the channel layer; The plurality of gate electrodes are spaced apart from the source electrode and the drain electrode and are located between the source electrode and the drain electrode; the gate electrode has an extended end, and in the length direction of the gate electrode, the extended end protrudes from the source electrode, the drain electrode, the channel layer and the dielectric layer; A biological probe is fixed on a surface of the extended end away from the medium layer.

2. The biosensor according to claim 1, wherein The gate electrode also has a connecting portion, which is detachably connected to the extended end, and the biological probe is fixed on the surface of the connecting portion.

3. The biosensor according to claim 2, wherein: The biosensor further comprises a sample slot for receiving a sample to be tested, and the sample slot is arranged on the surface of the connecting part.

4. The biosensor according to any one of claims 1 to 3, wherein The biological probe capable of specifically binding to different target detection objects is fixed on each of the extension ends.

5. The biosensor according to any one of claims 1 to 4, wherein The dielectric layer covers the surface of the substrate where no channel layer is provided.

6. The biosensor according to any one of claims 1 to 5, wherein A surface of the gate electrode close to the substrate is flush with a surface of the dielectric layer away from the substrate.

7. The biosensor according to any one of claims 1 to 6, wherein: The material of the channel layer includes at least one of graphene, transition metal dichalcogenide, silicon, oxide semiconductor and polymer semiconductor.

8. The biosensor according to any one of claims 1 to 7, wherein The material of the dielectric layer includes at least one of zirconium oxide and hafnium oxide.

9. The biosensor according to any one of claims 1 to 8, wherein The substrate includes one of glass, silicon dioxide, sapphire and mica.

10. The biosensor according to any one of claims 1 to 9, wherein The biological probe includes at least one of an antibody, an antigen, an enzyme, RNA, PNA, a single-stranded DNA, a double-stranded DNA, a two-dimensional DNA nanostructure, and a three-dimensional DNA nanostructure.

11. The biosensor according to any one of claims 1 to 10, wherein: The material of the source electrode is selected from at least one of gold, silver, copper, titanium, chromium, carbon materials and conductive polymer materials.

12. The biosensor according to any one of claims 1 to 11, wherein: The material of the drain electrode is selected from at least one of gold, silver, copper, titanium, chromium, carbon materials and conductive polymer materials.

13. The biosensor according to any one of claims 1 to 12, wherein: The material of the gate electrode is selected from at least one of gold, silver, copper, titanium, chromium, carbon materials and conductive polymer materials.

14. The biosensor according to any one of claims 1 to 13, wherein: The thickness of the source electrode is 20nm-500nm.

15. The biosensor according to any one of claims 1 to 14, wherein: The thickness of the drain electrode is 20nm-500nm.

16. The biosensor according to any one of claims 1 to 15, wherein: The thickness of the gate electrode is 20nm-500nm.

17. A detection kit comprising: The biosensor according to any one of claims 1 to 16.

18. A detection device comprising: The biosensor according to any one of claims 1 to 16 or the detection kit according to claim 17.

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