Preparation of high-performance organic electrochemical transistor and application of high-performance organic electrochemical transistor in biosensing

Abstract

The invention relates to preparation of a high-performance organic electrochemical transistor and application of the high-performance organic electrochemical transistor in biosensing, the organic electrochemical transistor comprises a grid electrode, a source electrode, a drain electrode and a channel, the channel is located between the source electrode and the drain electrode, the grid electrode is formed by modifying a ferrocene functionalized and bionic functionalized conductive polymer copolymer material on the surface of a gold substrate, and the channel is formed by modifying ferrocene functionalized and bionic functionalized conductive polymer copolymer material on the surface of the gold substrate. The ferrocene functionalized and bionic functionalized conductive polymer copolymer material is an EDOT copolymer containing a ferrocene group side chain and a bionic group side chain; the biosensor is obtained by performing photoetching patterning on the surface of a substrate, depositing a source electrode, a drain electrode, a grid electrode and a connecting circuit, depositing a packaging passivation layer, exposing a window capable of forming a channel, the source electrode, the drain electrode and the grid electrode, and finally preparing a functionalized grid electrode. The transconductance is increased by improving the gate capacitance, the detection sensitivity is improved by improving the gate charge transfer capability, and the detection limit is reduced; the probe is used for targeted recognition of cells, viruses and biomolecules. The preparation method disclosed by the invention is simple in process, and the prepared product can improve the transconductance of the organic electrochemical transistor, improve the sensing detection sensitivity and reduce the detection limit at the same time.

Description

Technical Field

[0001] The invention belongs to the technical field of biosensors, and relates to the preparation of a high-performance organic electrochemical transistor and its application in biosensors. Background Art

[0002] Organic electrochemical transistors (OECTs) have gradually attracted people's attention due to their high signal amplification ability, high sensitivity, low cost, easy manufacturing, and stable operation in aqueous solution. They are considered to have the potential to achieve non-labeled and highly sensitive detection of trace biomarkers. Their structure includes a source, a drain, and a gate, and an organic semiconductor is mounted between the source and the drain to form a channel. A small change in the gate current can cause a large change in the current between the source and the drain.

[0003] Transconductance (g m ) is defined as the derivative of the drain current with respect to the gate voltage and is considered the most critical performance parameter of OECTs and an important indicator for evaluating their ability to effectively amplify electrical signals. Higher transconductance can significantly enhance the amplification effect of weak signals, which is particularly important for the detection of low-concentration biomarkers.

[0004] Therefore, in order to further improve the sensing performance, it is particularly important to improve the transconductance of OECT. In terms of improving the transconductance of OECT, researchers face many challenges. For example, document 1 (Advanced Materials, 2024, 36 (1), 2310503.) points out that in order to improve the channel carrier mobility, finding high conductivity, high electron mobility and new organic semiconductor channel materials has become an important research direction. However, the current n-type semiconductor polymers with high carrier mobility are unstable in the air, and their applicability cannot be compared with PEDOT:PSS. Secondly, document 2 (Advanced Functional Materials, 2007, 17 (17): 3538-3544.) and document 3 (Advanced Materials, 2018, 30 (5): 1705031.) report that optimizing the device structure and preparation process of OECT is also the key to improving transconductance. However, for devices with small channel lengths, they still face problems such as demanding manufacturing processes and difficult processing. In addition, it is reported in document 4 (Flexible and Printed Electronics, 2018, 3:034002) that although gate materials with large capacitance can bring large transconductance and high signal amplification capability to OECT, in biosensing, it may cause insufficient disturbance of surrounding charges and reduce sensing sensitivity.

[0005] In summary, the current challenges of OECTs are still focused on improving device transconductance and sensing sensitivity, which is inseparable from the gate / electrolyte interface. When the gate capacitance increases, the transconductance of the OECT device will increase and the signal amplification capability will be enhanced. However, excessive capacitance will reduce the sensing sensitivity of the gate / electrolyte interface. In order to improve the transconductance and sensing performance of OECTs, it is necessary to find a material with high capacitance and high charge transfer capability to modify the gate. Summary of the invention

[0006] The purpose of the present invention is to solve the above problems existing in the prior art and to provide a method for preparing a high-performance organic electrochemical transistor and its application in biosensing.

[0007] To achieve the above object, the technical solution adopted by the present invention is as follows:

[0008] A preparation of a high-performance organic electrochemical transistor and its application in biosensing, wherein the organic electrochemical transistor includes a gate, a source, a drain and a channel, wherein the channel is between the source and the drain, and the gate is a conductive polymer copolymer material modified with ferrocene functionalization and bionic functionalization on the surface of a gold substrate, wherein the ferrocene functionalization and bionic functionalization conductive polymer copolymer material is an EDOT copolymer containing ferrocene group side chains and zwitterionic group side chains; the biosensor is obtained by photolithographic patterning on the surface of the substrate, and then depositing the source, drain, gate and connecting lines, and then depositing an encapsulation passivation layer thereon, and then exposing a window that can form a channel as well as the source, drain and gate, and finally preparing a functionalized gate; it is used for targeted identification of cells, viruses and biological molecules. The preparation method of the present invention is simple in process, and the obtained product can improve the transconductance of the organic electrochemical transistor while improving the sensing detection sensitivity and reducing the detection limit;

[0009] Compared with the organic electrochemical transistor biosensor based on gold gate electrode, the high-performance organic electrochemical transistor transconductance of the present invention is significantly improved, which is not less than 1.4 times; the increase in transconductance comes from the gate-modified EDOT copolymer containing ferrocene group side chains and biomimetic group side chains, which can increase the capacitance of the gate and electrolyte interface, thereby improving transconductance. And using this ferrocene group with a high electron transfer rate constant as a gate modification material, after the positive voltage is applied to the gate of the OECT, the ferrocene group itself undergoes an oxidation reaction and becomes positively charged, causing greater charge disturbance on both sides of the electrolyte solution, thereby improving its sensitivity in biosensing detection and reducing the detection limit.

[0010] As the preferred technical solution:

[0011] In the high-performance organic electrochemical transistor as described above, the gate is a ferrocene-functionalized and biomimetic-functionalized conductive polymer material, and the ferrocene-functionalized and biomimetic-functionalized conductive polymer material is an EDOT copolymer containing a ferrocene group side chain and a zwitterionic group side chain. The ferrocene group with a large capacitance can improve the OECT transconductance and achieve high signal amplification performance.

[0012] As described above, a high-performance organic electrochemical transistor biosensor comprises a ferrocene-functionalized and biomimetic-functionalized conductive polymer copolymer material and a conductive polymer with a bio-coupling group side chain; the gate sensing interface may further contain a bio-coupling group to achieve specific capture of biological molecules such as proteins and viruses. The ferrocene group with a high electron transfer rate constant can be oxidized to a positively charged ferrocene ion after a positive voltage is applied to the gate, thereby causing a greater disturbance in the charge in the electrolyte solution during the biosensing process, making the current change more obvious and thus improving the sensing sensitivity.

[0013] A high-performance organic electrochemical transistor as described above, wherein the monomer unit structure where the zwitterionic group side chain in the biomimetic functional conductive polymer material is located is shown in formula (I);

[0014]

[0015] In formula (I):

[0016] It is a repeating unit constituting the main chain of the conductive polymer;

[0017] -L 1 -for-(CH 2 ) x1 -、-(CH 2 ) x1 -O-(CH 2 ) y1 -、-(CH2) x1 -O-CO-(CH 2 ) y1 -、-(CH 2 ) x1 -(CH 2 -CH 2 -O) y1 -、-(CH 2 ) x1 -O-(CH 2 -CH 2 -O) y1 -、-O-(CH 2 ) x1 -(CH 2 -CH 2 -O) y1- and -O-(CH 2 ) x1 -O-(CH 2 -CH 2 -O) y1 -, wherein x1 and y1 are integers, and 0≤x1≤20, 0≤y1≤20;

[0018] -L 2 -for-(CH 2 ) x2 -、-(CH 2 ) x2 -O-, -CO-O-(CH 2 ) x2 -、-O-CO-(CH 2 ) x2 -、-CO-NH-(CH 2 ) x2 -、-C(CH 3 ) 2 -CO-O-(CH 2 ) x2 、-CH(CH 3 )-O-(CH 2 ) x2 、-S-CH 2 -CH 2 -O-(CH 2 ) x2 and-S-CH 2 -CH(CH 3 )-CO-O-(CH 2 ) x2 One or more of , wherein x2 is an integer and 0≤x2≤20;

[0019] -R 2 for

[0020] A high-performance organic electrochemical transistor as described above, wherein the monomer unit structure of the biomimetic functional conductive polymer material where the bio-coupling group side chain is located is shown in formula (II);

[0021]

[0022] In formula (II):

[0023] It is a repeating unit constituting the main chain of the conductive polymer;

[0024] -L 3 -for-(CH 2 ) x3 -、-(CH 2 )x3 -O-(CH 2 ) y3 -、-(CH2) x3 -O-CO-(CH 2 ) y3 -、-(CH 2 ) x3 -NH-CO-O-, -(CH 2 ) x3 -(CH 2 -CH 2 -O) y3 -、-(CH 2 ) x3 -O-(CH 2 -CH 2 -O) y3 -、-O-(CH 2 ) x33 -(CH 2 -CH 2 -O) y3 - and -O-(CH 2 ) x3 -O-(CH 2 -CH 2 -O) y3 -, wherein x3 and y3 are integers, and 0≤x3≤20, 0≤y3≤20;

[0025] -L 4 -is -O-, -CO-O-, -O-CH 2 -CO-O-, -S-(CH 2 ) x4 -CO-O-(CH 2 ) y4 -、-CO-NH-(CH 2 ) x4 -、-NH-(CH 2 ) x4 -、-NH-CO-(CH 2 ) x4 -、-O-CO-(CH 2 ) x4 -、-CO-NH-(CH 2 ) x4 -、 One or more of, wherein x4 and y4 are integers, and 0≤x4≤20, 0≤y4≤20;

[0026] -R 3 -COOH, -NH 2 、-O-NH 2、-N 3 ,

[0027] For a high-performance organic electrochemical transistor as described above, the monomer unit structure where the ferrocene group side chain in the ferrocene functionalized conductive polymer material is located is shown in formula (III);

[0028]

[0029] In formula (I):

[0030] It is a repeating unit constituting the main chain of the conductive polymer;

[0031] -L 5 -for-(CH 2 ) x5 -、-(CH 2 ) x5 -O-(CH 2 ) y5 -、-(CH2) x5 -O-CO-(CH 2 ) y5 -、-(CH 2 ) x5 -(CH 2 -CH 2 -O) y5 -、

[0032] -(CH 2 ) x5 -O-(CH 2 -CH 2 -O) y5 -、-O-(CH 2 ) x5 -(CH 2 -CH 2 -O) y5 - and -O-(CH 2 ) x5 -O-(CH 2 -CH 2 -O) y5 -, wherein x5 and y5 are integers, and 0≤x5≤20, 0≤y5≤20;

[0033] -L 6 -for-(CH 2 ) x6 -、-(CH 2 ) x6 -O-, -CO-O-(CH 2 ) x6 -、-O-CO-(CH2 ) x6 -、-CO-NH-(CH 2 ) x6 -、-C(CH 3 ) 2 -CO-O-(CH 2 ) x6 、-CH(CH 3 )-O-(CH 2 ) x6 、-S-CH 2 -CH 2 -O-(CH 2 ) x6 and-S-CH 2 -CH(CH 3 )-CO-O-(CH 2 ) x6 One or more of , wherein x6 is an integer and 0≤x6≤20;

[0034] -R 4 It is ferrocene and its derivatives, catechol and its derivatives or hydroquinone and its derivatives.

[0035] A high performance organic electrochemical transistor biosensor as described above, Independently selected from Any one of .

[0036] The present invention also provides a method for preparing a high-performance organic electrochemical transistor as described in any one of the above items, comprising the following steps:

[0037] (1) performing photolithographic patterning on the substrate surface, and then depositing the source, drain, gate and connecting lines;

[0038] (2) After the source electrode, drain electrode, gate electrode and connecting lines are deposited, a package passivation layer is deposited to package the source electrode, drain electrode, gate electrode and connecting lines, and then a window for forming a channel as well as the source electrode, drain electrode and gate electrode are exposed by photolithography and plasma dry etching processes;

[0039] (3) PEDOT:PSS is spin-coated on a window that can form a channel to prepare a channel, and a ferrocene-functionalized and biomimetic-functionalized conductive polymer copolymer material is modified on the gate to prepare a gate. The source, drain, biomimetic gate, and the channel between the source and drain together constitute a high-performance organic electrochemical transistor.

[0040] As the preferred technical solution:

[0041] The method for preparing a high-performance organic electrochemical transistor as described above comprises modifying a ferrocene functionalized conductive polymer material on a gate electrode by an electrochemical polymerization method.

[0042] The present invention also provides an application of a biosensor of a high-performance organic electrochemical transistor as described in any of the above items, which is used for targeted recognition of biological molecules such as proteins and viruses. The biosensor of a high-performance organic electrochemical transistor of the present invention improves the transconductance performance of OECT while improving the biosensor detection sensitivity and reducing the sensor detection limit.

[0043] Principle of the invention:

[0044] The present invention uses ferrocene group functionalized and biomimetic functionalized conductive copolymers as functionalized materials for OECT to improve the transconductance of OECT and enhance the signal amplification performance, and further adds conductive polymers with bio-coupling groups for targeted recognition of biological molecules such as cells, viruses, proteins, etc., thereby improving the sensitivity of biosensors and reducing the detection limit.

[0045] Material modification at the gate can lead to an increase in gate capacitance, thereby reducing the voltage drop at the gate electrode. As a result, ions in the electrolyte are more effectively injected into the channel and dedope the organic semiconductor material in the channel. As a result, the slope of the transfer curve becomes steeper and the transconductance increases. Therefore, the transconductance can be increased by increasing the gate capacitance.

[0046] Biofunctionalization is performed by using ferrocene as an electron mediator. Ferrocene (Fc) is a stable organic metal compound with good inherent properties (i.e., low molecular weight, good electrochemical stability, low potential reversibility, and the ability to form a stable redox state) and is often used in the field of biosensing. After adding the sample of the substrate to be tested, the charged analyte or enzyme is specifically captured by the material modified on the gate, causing a change in surface charge or an enzymatic reaction, and the ferrocene / ferro (Fc / Fc + ) cycle back, because ferrocene has a low oxidation potential and a high electron transfer rate constant, the mediating electron transfer rate is high, and the resulting change in channel current is proportional to the concentration of the substrate to be detected. Therefore, the sensitivity of biosensor detection can be improved by modifying the ferrocene group.

[0047] In addition, as a cell membrane-like component, the researchers found that the zwitterionic group can significantly inhibit the adsorption of proteins and the adhesion of cells, and has excellent biocompatibility and stability, which can enable OECT to maintain stable anti-fouling properties when detecting in complex body fluid environments.

[0048] In summary, the high-performance organic electrochemical transistor biosensor designed in the present invention can solve the technical problems that technicians in the field have been eager to solve but have not been able to solve successfully, and can improve the transconductance performance while improving the sensing sensitivity and reducing the detection limit.

[0049] Beneficial effects:

[0050] (1) The high-performance organic electrochemical transistor of the present invention can significantly improve the device transconductance by modifying the gate with a ferrocene-functionalized and biomimetic-functionalized conductive polymer copolymer material;

[0051] (2) The high-performance organic electrochemical transistor biosensor of the present invention can specifically detect C-reactive protein and H by introducing a conductive polymer copolymer material containing ferrocene functionalization and biomimetic functionalization and a coupleable biological group into the gate. 3 N 2 Influenza A virus N protein;

[0052] (3) The method for preparing the high-performance organic electrochemical transistor biosensor of the present invention has a simple process, strong operability, and is suitable for industrial production;

[0053] (4) The high-performance organic electrochemical transistor biosensor of the present invention is used for targeted recognition of cells, viruses and biological molecules, thereby improving the reliability and specificity of sensing detection. BRIEF DESCRIPTION OF THE DRAWINGS

[0054] Figure 1 The transfer curve and transconductance of the organic electrochemical transistor modified with gold gate (left), and the transfer curve and transconductance of the organic electrochemical transistor with ferrocene functionalized conductive polymer modified gate (right).

[0055] Figure 2 The transfer curve of the organic electrochemical transistor with a gold gate and a gate modified with ferrocene-functionalized and biomimetic-functionalized conductive polymer copolymers with different deposition amounts (left figure), and the transconductance of the organic electrochemical transistor with a gold gate and a gate modified with ferrocene-functionalized and biomimetic-functionalized conductive polymer copolymers with different deposition amounts obtained by derivation of the left figure (right figure).

[0056] Figure 3 The transfer curve of the organic electrochemical transistor with a gate modified with ferrocene-functionalized and biomimetic-functionalized conductive polymer copolymers deposited during 5 cycles of cyclic voltammetry scanning for sensing of different concentrations of C-reactive protein (left figure), and the response relationship between the current change and the C-reactive protein concentration when measuring different concentrations (right figure).

[0057] Figure 4The cyclic voltammetry curves were scanned for 5 cycles. The organic electrochemical transistors with gates modified with ferrocene-functionalized and biomimetic-functionalized conductive polymer copolymers and bio-coupled groups were used for different concentrations of H 3 N 2 Transfer curve of influenza A virus N protein sensing detection (left), current change and H 3 N 2 Response relationship between influenza A virus N protein concentrations (right). DETAILED DESCRIPTION

[0058] The present invention will be further described below in conjunction with specific embodiments. It should be understood that these embodiments are only used to illustrate the present invention and are not intended to limit the scope of the present invention. In addition, it should be understood that after reading the content taught by the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms fall within the scope limited by the appended claims of the application equally.

[0059] The test methods involved in the embodiments are as follows:

[0060] Transfer curves: The high-performance organic electrochemical transistor biosensor was tested using a Keithley 2636B dual-channel source meter; performance characterization was performed in PBS solution with a pH of 7.4; the gate voltage ranged from -0.4 V to 0.8 V, and the source-drain voltage was -0.4 V.

[0061] Transconductance: Transconductance is defined as the first-order derivative of the transfer curve, which reflects the signal amplification capability of the OECT device. The higher the transconductance value, the stronger the signal amplification capability of the device.

[0062] Example 1

[0063] A method for preparing a high-performance organic electrochemical transistor, the specific steps are as follows:

[0064] (1) performing photolithographic patterning on the substrate surface, and then depositing a source electrode, a drain electrode, a gate electrode, and connecting lines all made of gold;

[0065] (2) After the source electrode, drain electrode, gate electrode and connecting lines are deposited, a polyparaxylene encapsulation passivation layer with a thickness of 30 μm is deposited to encapsulate the source electrode, drain electrode, gate electrode and connecting lines, and then a window for forming a channel as well as the source electrode, drain electrode and gate electrode are exposed by photolithography and plasma dry etching processes;

[0066] The process parameters of photolithography are: spin coating photoresist AZ9260 at a speed of 2000 rpm, followed by drying at 110°C for 180 seconds, and photolithography exposure time of 30 seconds;

[0067] The process parameters of plasma etching are: oxygen pressure 10Pa, power 400W, etching time 45min;

[0068] (3) Spin coating PEDOT:PSS (Heraeus, PH100) solution between the source and drain electrodes at 1500 rpm for 45 seconds, followed by annealing at 120 °C for 1 hour to prepare a PEDOT:PSS channel with a thickness of 150 nm, a length of 100 μm, and a width of 10 μm;

[0069] (4) Prepare the gate by modifying the biomimetic functional conductive polymer material on the gate using an electrochemical polymerization method: Weigh 3.8743 g of TBHAP into a reagent bottle containing 100 mL of anhydrous dichloromethane, stir overnight, and prepare a 100 mM TBHAP anhydrous dichloromethane electrolyte solution. Weigh 44 mg of Add 10mL of electrolyte solution and stir overnight to prepare EDOT-Fc electroplating solution with a monomer concentration of 10mM. Cyclic voltammetry electrochemical method was used for deposition during electropolymerization. A three-electrode system was selected, with a gold grid with a diameter of 2mm as the working electrode and Ag / AgNO 3 The organic phase electrode was used as the reference electrode, the platinum mesh was used as the counter electrode, and the potential scanning range was -0.6-1.4 V (relative to Ag / AgNO 3 ), the scanning rate is 0.1V / s, and the scanning is 2 circles.

[0070] (5) The source electrode, the drain electrode, the ferrocene-functionalized gate electrode, and the channel between the source electrode and the drain electrode together constitute a high-performance organic electrochemical transistor biosensor.

[0071] like Figure 1 As shown in the figure, the high-performance organic electrochemical transistor was tested for electrical performance in PBS buffer. After taking a derivative of the transfer curve, the transconductance value was calculated. The modified OECT showed a higher transconductance value of 8.34mS. This value is about 1.25 times higher than the 6.65mS before modification.

[0072] Example 2

[0073] A method for preparing a high-performance organic electrochemical transistor biosensor, the specific steps are as follows:

[0074] (1) performing photolithographic patterning on the substrate surface, and then depositing a source electrode, a drain electrode, a gate electrode, and connecting lines all made of gold;

[0075] (2) After the source electrode, drain electrode, gate electrode and connecting lines are deposited, a polyparaxylene encapsulation passivation layer with a thickness of 30 μm is deposited to encapsulate the source electrode, drain electrode, gate electrode and connecting lines, and then a window for forming a channel as well as the source electrode, drain electrode and gate electrode are exposed by photolithography and plasma dry etching processes;

[0076] The process parameters of photolithography are: spin coating photoresist AZ9260 at a speed of 2000 rpm, followed by drying at 110°C for 180 seconds, and photolithography exposure time of 30 seconds;

[0077] The process parameters of plasma etching are: oxygen pressure 10Pa, power 400W, etching time 45min;

[0078] (3) Spin-coat a PEDOT:PSS (Heraeus, PH100) solution between the source and drain electrodes at 1500 rpm for 45 s, and then anneal at 120 °C for 1 h to prepare a PEDOT:PSS channel with a thickness of 150 nm, a length of 20 μm, and a width of 40 μm;

[0079] (4) Using electrochemical polymerization method to modify the biomimetic functional conductive polymer material on the gold gate: weigh 4.4 mg 10.64mg LiClO 4 To 1mL 1-ethyl-3-methylimidazolium tetrafluoroborate ([EMIM][BF4]) ionic liquid, prepare a plating solution with a monomer concentration of 20mM; weigh 6.74mg 10.64mg LiClO 4 To 1mL 1-ethyl-3-methylimidazolium tetrafluoroborate ([EMIM][BF4]) ionic liquid, a plating solution with a monomer concentration of 20mM was prepared, stirred overnight, and then prepared in a ratio of 30% and 70% respectively. The potential scanning range was -0.4-1.3V (relative to Ag / AgCl), the scanning rate was 0.1V / s, and the number of scanning circles was 1 circle.

[0080] (5) The source electrode, the drain electrode, the bionic gate electrode, and the channel between the source electrode and the drain electrode together constitute a high-performance organic electrochemical transistor biosensor.

[0081] like Figure 2 As shown, the electrical performance of a high-performance organic electrochemical transistor was tested in PBS buffer. The transconductance value was calculated after taking the derivative of the transfer curve. The gate with more deposited electricity had a maximum transconductance of 10.56mS for the OECT, which was 1.4 times higher than the 7.6mS of the gold gate, and had a lower operating voltage.

[0082] like Figure 3As shown, a biosensor based on a high-performance organic electrochemical transistor is used to specifically sense and detect C-reactive protein. In this experiment, the transfer curve is measured three times and the relationship between the current change value and the concentration is calculated, and an error bar analysis is performed.

[0083] Comparative Example 2

[0084] A method for preparing a biosensor based on an organic electrochemical transistor is basically the same as in Example 2, except that in step (4), a conductive polymer material is modified on the gate electrode by an electrochemical polymerization method: 1.02 mg of 4.7mg and 10.64 mg of LiClO 4 Add to 1mL 1-ethyl-3-methylimidazolium tetrafluoroborate ([EMIM][BF4]) ionic liquid to prepare a total concentration of 20mM, with the ratio of the two being 30% and 70% respectively. Use the gate as the working electrode, the platinum mesh as the counter electrode, and Ag / AgCl as the reference electrode to perform polymerization using scanning cyclic voltammetry, with a scanning range of -0.6 to 1.13V, a scanning speed of 100mV / s, and a scanning cycle of 1 circle to obtain a gate modified with a conductive polymer material;

[0085] The electrical performance of the high-performance organic electrochemical transistor was tested in PBS buffer, and the transconductance was calculated after taking a derivative of the transfer curve.

[0086] As shown, a biosensor based on a high-performance organic electrochemical transistor is used to specifically sense and detect C-reactive protein. In this experiment, the transfer curve is measured three times and the relationship between the current change value and the concentration is calculated, and an error bar analysis is performed.

[0087] Example 3

[0088] A method for preparing a high-performance organic electrochemical transistor biosensor, the specific steps are as follows:

[0089] (1) performing photolithographic patterning on the substrate surface, and then depositing a source electrode, a drain electrode, a gate electrode, and connecting lines all made of gold;

[0090] (2) After the source electrode, drain electrode, gate electrode and connecting lines are deposited, a polyparaxylene encapsulation passivation layer with a thickness of 30 μm is deposited to encapsulate the source electrode, drain electrode, gate electrode and connecting lines, and then a window for forming a channel as well as the source electrode, drain electrode and gate electrode are exposed by photolithography and plasma dry etching processes;

[0091] The process parameters of photolithography are: spin coating photoresist AZ9260 at a speed of 2000 rpm, followed by drying at 110°C for 180 seconds, and photolithography exposure time of 30 seconds;

[0092] The process parameters of plasma etching are: oxygen pressure 10Pa, power 400W, etching time 45min;

[0093] (3) Spin-coat a PEDOT:PSS (Heraeus, PH100) solution between the source and drain electrodes at 1500 rpm for 45 s, and then anneal at 120 °C for 1 h to prepare a PEDOT:PSS channel with a thickness of 150 nm, a length of 20 μm, and a width of 40 μm;

[0094] (4) Modifying the biomimetic functional conductive polymer material on the gold gate by electrochemical polymerization: and LiClO 4 The electroplating solution was prepared in 1-ethyl-3-methylimidazolium tetrafluoroborate ([EMIM][BF4]) ionic liquid with a monomer concentration of 20 mM; the ratios of the two monomers were 30% and 70%, respectively. The potential scanning range was -0.4-1.3 V (relative to Ag / AgCl), the scanning rate was 0.1 V / s, and the number of scanning cycles was 3 cycles.

[0095] (5) The source, drain, bionic gate, and channel between the source and drain together constitute a high-performance organic electrochemical transistor biosensor.

[0096] The electrical performance of high-performance organic electrochemical transistors was tested in PBS buffer, and the transconductance was calculated after taking the derivative of the transfer curve.

[0097] Example 4

[0098] A method for preparing a high-performance organic electrochemical transistor biosensor, the specific steps are as follows:

[0099] (1) performing photolithographic patterning on the substrate surface, and then depositing a source electrode, a drain electrode, a gate electrode, and connecting lines all made of gold;

[0100] (2) After the source electrode, drain electrode, gate electrode and connecting lines are deposited, a polyparaxylene encapsulation passivation layer with a thickness of 30 μm is deposited to encapsulate the source electrode, drain electrode, gate electrode and connecting lines, and then a window for forming a channel as well as the source electrode, drain electrode and gate electrode are exposed by photolithography and plasma dry etching processes;

[0101] The process parameters of photolithography are: spin coating photoresist AZ9260 at a speed of 2000 rpm, followed by drying at 110°C for 180 seconds, and photolithography exposure time of 30 seconds;

[0102] The process parameters of plasma etching are: oxygen pressure 10Pa, power 400W, etching time 45min;

[0103] (3) Spin-coat a PEDOT:PSS (Heraeus, PH100) solution between the source and drain electrodes at 1500 rpm for 45 s, and then anneal at 120 °C for 1 h to prepare a PEDOT:PSS channel with a thickness of 150 nm, a length of 20 μm, and a width of 40 μm;

[0104] (4) Modifying the biomimetic functional conductive polymer material on the gold gate by electrochemical polymerization: and LiClO 4 The electroplating solution was prepared in 1-ethyl-3-methylimidazolium tetrafluoroborate ([EMIM][BF4]) ionic liquid with a monomer concentration of 20 mM; the ratios of the two monomers were 30% and 70%, respectively. The potential scanning range was -0.4-1.3 V (relative to Ag / AgCl), the scanning rate was 0.1 V / s, and the number of scanning cycles was 5.

[0105] (5) The source electrode, the drain electrode, the bionic gate electrode, and the channel between the source electrode and the drain electrode together constitute a high-performance organic electrochemical transistor biosensor.

[0106] The electrical performance of high-performance organic electrochemical transistors was tested in PBS buffer, and the transconductance was calculated after taking the derivative of the transfer curve.

[0107] Example 5

[0108] A method for preparing a high-performance organic electrochemical transistor biosensor, the specific steps are as follows:

[0109] (1) performing photolithographic patterning on the substrate surface, and then depositing a source electrode, a drain electrode, a gate electrode, and connecting lines all made of gold;

[0110] (2) After the source electrode, drain electrode, gate electrode and connecting lines are deposited, a polyparaxylene encapsulation passivation layer with a thickness of 30 μm is deposited to encapsulate the source electrode, drain electrode, gate electrode and connecting lines, and then a window for forming a channel as well as the source electrode, drain electrode and gate electrode are exposed by photolithography and plasma dry etching processes;

[0111] The process parameters of photolithography are: spin coating photoresist AZ9260 at a speed of 2000 rpm, followed by drying at 110°C for 180 seconds, and photolithography exposure time of 30 seconds;

[0112] The process parameters of plasma etching are: oxygen pressure 10Pa, power 400W, etching time 45min;

[0113] (3) Spin-coat a PEDOT:PSS (Heraeus, PH100) solution between the source and drain electrodes at 1500 rpm for 45 s, and then anneal at 120 °C for 1 h to prepare a PEDOT:PSS channel with a thickness of 150 nm, a length of 20 μm, and a width of 40 μm;

[0114] (4) Using electrochemical polymerization method to modify biomimetic functional conductive polymer materials on the gold gate: and LiClO 4 Dissolved in 1 mL of 1-ethyl-3-methylimidazolium tetrafluoroborate ([EMIM][BF4]) ionic liquid, the monomer concentration was 20 mM, and the monomer concentrations were 30%, 60%, and 10%, respectively. The copolymerization reaction was carried out by cyclic voltammetry electrochemical method in the potential range of -0.4 V to 1.3 V (relative to Ag / AgCl reference electrode), with a scan rate of 0.1 V / s and a scan number of 1 circle.

[0115] (5) The source, drain, bionic gate, and channel between the source and drain together constitute a high-performance organic electrochemical transistor biosensor.

[0116] High-performance organic electrochemical transistor-based biosensor for specific detection of H 3 N 2 Influenza A virus N protein, this experiment measured the transfer curve three times and calculated the relationship between the current change value and the concentration, and made an error bar analysis.

[0117] Comparative Example 5

[0118] A method for preparing a high-performance organic electrochemical transistor biosensor, the specific steps are as follows:

[0119] (1) performing photolithographic patterning on the substrate surface, and then depositing a source electrode, a drain electrode, a gate electrode, and connecting lines all made of gold;

[0120] (2) After the source electrode, drain electrode, gate electrode and connecting lines are deposited, a polyparaxylene encapsulation passivation layer with a thickness of 30 μm is deposited to encapsulate the source electrode, drain electrode, gate electrode and connecting lines, and then a window for forming a channel as well as the source electrode, drain electrode and gate electrode are exposed by photolithography and plasma dry etching processes;

[0121] The process parameters of photolithography are: spin coating photoresist AZ9260 at a speed of 2000 rpm, followed by drying at 110°C for 180 seconds, and photolithography exposure time of 30 seconds;

[0122] The process parameters of plasma etching are: oxygen pressure 10Pa, power 400W, etching time 45min;

[0123] (3) Spin-coat a PEDOT:PSS (Heraeus, PH100) solution between the source and drain electrodes at 1500 rpm for 45 s, and then anneal at 120 °C for 1 h to prepare a PEDOT:PSS channel with a thickness of 150 nm, a length of 20 μm, and a width of 40 μm;

[0124] (4) Using electrochemical polymerization method to modify biomimetic functional conductive polymer materials on the gold gate: and LiClO 4 Dissolved in 1 mL of 1-ethyl-3-methylimidazolium tetrafluoroborate ([EMIM][BF4]) ionic liquid, the monomer concentration was 20 mM, and the monomer concentrations were 30%, 60%, and 10%, respectively. The copolymerization reaction was carried out by cyclic voltammetry electrochemical method in the potential range of -0.4 V to 1.3 V (relative to Ag / AgCl reference electrode), with a scan rate of 0.1 V / s and a scan number of 1 circle.

[0125] (5) The source electrode, the drain electrode, the bionic gate electrode, and the channel between the source electrode and the drain electrode together constitute a high-performance organic electrochemical transistor biosensor.

[0126] High-performance organic electrochemical transistor-based biosensor for specific detection of H 3 N 2 Influenza A virus N protein, this experiment measured the transfer curve three times and calculated the relationship between the current change value and the concentration, and made an error bar analysis.

[0127] Example 6

[0128] A method for preparing a high-performance organic electrochemical transistor biosensor, the specific steps are as follows:

[0129] (1) performing photolithographic patterning on the substrate surface, and then depositing a source electrode, a drain electrode, a gate electrode, and connecting lines all made of gold;

[0130] (2) After the source electrode, drain electrode, gate electrode and connecting lines are deposited, a polyparaxylene encapsulation passivation layer with a thickness of 30 μm is deposited to encapsulate the source electrode, drain electrode, gate electrode and connecting lines, and then a window for forming a channel as well as the source electrode, drain electrode and gate electrode are exposed by photolithography and plasma dry etching processes;

[0131] The process parameters of photolithography are: spin coating photoresist AZ9260 at a speed of 2000 rpm, followed by drying at 110°C for 180 seconds, and photolithography exposure time of 30 seconds;

[0132] The process parameters of plasma etching are: oxygen pressure 10Pa, power 400W, etching time 45min;

[0133] (3) Spin-coat a PEDOT:PSS (Heraeus, PH100) solution between the source and drain electrodes at 1500 rpm for 45 s, and then anneal at 120 °C for 1 h to prepare a PEDOT:PSS channel with a thickness of 150 nm, a length of 20 μm, and a width of 40 μm;

[0134] (4) Using electrochemical polymerization method to modify biomimetic functional conductive polymer materials on the gold gate: and LiClO 4 Dissolved in 1 mL of 1-ethyl-3-methylimidazolium tetrafluoroborate ([EMIM][BF4]) ionic liquid, the electroplating solution was prepared with a monomer concentration of 20 mM, and the monomer concentrations were 30%, 60%, and 10%, respectively. The copolymerization reaction was carried out by cyclic voltammetry electrochemical method in the potential range of -0.4 V to 1.3 V (relative to Ag / AgCl reference electrode), with a scan rate of 0.1 V / s and 3 scans.

[0135] (5) The source, drain, bionic gate, and channel between the source and drain together constitute a high-performance organic electrochemical transistor biosensor.

[0136] High-performance organic electrochemical transistor-based biosensor for specific detection of H 3 N 2 Influenza A virus N protein, this experiment measured the transfer curve three times and calculated the relationship between the current change value and the concentration, and made an error bar analysis.

[0137] Example 7

[0138] A method for preparing a high-performance organic electrochemical transistor biosensor, the specific steps are as follows:

[0139] (1) performing photolithographic patterning on the substrate surface, and then depositing a source electrode, a drain electrode, a gate electrode, and connecting lines all made of gold;

[0140] (2) After the source electrode, drain electrode, gate electrode and connecting lines are deposited, a polyparaxylene encapsulation passivation layer with a thickness of 30 μm is deposited to encapsulate the source electrode, drain electrode, gate electrode and connecting lines, and then a window for forming a channel as well as the source electrode, drain electrode and gate electrode are exposed by photolithography and plasma dry etching processes;

[0141] The process parameters of photolithography are: spin coating photoresist AZ9260 at a speed of 2000 rpm, followed by drying at 110°C for 180 seconds, and photolithography exposure time of 30 seconds;

[0142] The process parameters of plasma etching are: oxygen pressure 10Pa, power 400W, etching time 45min;

[0143] (3) Spin-coat a PEDOT:PSS (Heraeus, PH100) solution between the source and drain electrodes at 1500 rpm for 45 s, and then anneal at 120 °C for 1 h to prepare a PEDOT:PSS channel with a thickness of 150 nm, a length of 20 μm, and a width of 40 μm;

[0144] (4) Using electrochemical polymerization method to modify biomimetic functional conductive polymer materials on the gold gate: and LiClO 4 Dissolved in 1 mL of 1-ethyl-3-methylimidazolium tetrafluoroborate ([EMIM][BF4]) ionic liquid, the electroplating solution was prepared with a monomer concentration of 20 mM, and the monomer concentrations were 30%, 60%, and 10%, respectively. The copolymerization reaction was carried out by cyclic voltammetry electrochemical method in the potential range of -0.4 V to 1.3 V (relative to Ag / AgCl reference electrode), with a scan rate of 0.1 V / s and 5 scans.

[0145] (5) The source, drain, bionic gate, and channel between the source and drain together constitute a high-performance organic electrochemical transistor biosensor.

[0146] High-performance organic electrochemical transistor-based biosensor for specific detection of H 3 N 2 Influenza A virus N protein, this experiment measured the transfer curve three times and calculated the relationship between the current change value and the concentration, and made an error bar analysis.

[0147] Example 8

[0148] A method for preparing a high-performance organic electrochemical transistor biosensor, the specific steps are as follows:

[0149] (1) performing photolithographic patterning on the substrate surface, and then depositing a source electrode, a drain electrode, a gate electrode, and connecting lines all made of gold;

[0150] (2) After the source electrode, drain electrode, gate electrode and connecting lines are deposited, a polyparaxylene encapsulation passivation layer with a thickness of 30 μm is deposited to encapsulate the source electrode, drain electrode, gate electrode and connecting lines, and then a window for forming a channel as well as the source electrode, drain electrode and gate electrode are exposed by photolithography and plasma dry etching processes;

[0151] The process parameters of photolithography are: spin coating photoresist AZ9260 at a speed of 2000 rpm, followed by drying at 110°C for 180 seconds, and photolithography exposure time of 30 seconds;

[0152] The process parameters of plasma etching are: oxygen pressure 10Pa, power 400W, etching time 45min;

[0153] (3) Spin-coat a PEDOT:PSS (Heraeus, PH100) solution between the source and drain electrodes at 1500 rpm for 45 s, and then anneal at 120 °C for 1 h to prepare a PEDOT:PSS channel with a thickness of 150 nm, a length of 20 μm, and a width of 40 μm;

[0154] (4) Using electrochemical polymerization method to modify biomimetic functional conductive polymer materials on the gold gate: and LiClO 4 Dissolved in 1 mL of 1-ethyl-3-methylimidazolium tetrafluoroborate ([EMIM][BF4]) ionic liquid, the electroplating solution was prepared with a monomer concentration of 20 mM, and the monomer concentrations were 30%, 60%, and 10%, respectively. The copolymerization reaction was carried out by cyclic voltammetry electrochemical method in the potential range of -0.4 V to 1.3 V (relative to Ag / AgCl reference electrode), with a scan rate of 0.1 V / s and 5 scans.

[0155] (5) The source, drain, bionic gate, and channel between the source and drain together constitute a high-performance organic electrochemical transistor biosensor.

[0156] High-performance organic electrochemical transistor-based biosensor for specific detection of H 3 N 2 Influenza A virus N protein, this experiment measured the transfer curve three times and calculated the relationship between the current change value and the concentration, and made an error bar analysis.

Claims

1. A high-performance organic electrochemical transistor biosensor, comprising a source electrode, a drain electrode and a gate electrode, wherein a channel is provided between the source electrode and the drain electrode, wherein: The gate is a conductive polymer copolymer material modified with ferrocene functionalization and biomimetic functionalization on the surface of a gold substrate; The transconductance of the high-performance organic electrochemical transistor is increased by at least 1.4 times compared with that before modification; it has a higher detection sensitivity for biological molecules such as proteins, viruses, and cells.

2. A biosensor based on a high-performance organic electrochemical transistor according to claim 1, characterized in that: The biomimetic functionalized conductive polymer material in the gate material is a conductive polymer containing zwitterionic group side chains.

3. A biosensor based on a high-performance organic electrochemical transistor according to claims 1 and 2, characterized in that: The biomimetic functionalized conductive polymer material in the gate material is a conductive polymer containing zwitterionic group side chains and bio-coupling group side chains.

4. A high performance organic electrochemical transistor biosensor according to claims 1-3, characterized in that: The monomer unit structure where the zwitterionic group side chain is located in the biomimetic functional conductive polymer material is shown in formula (I); In formula (I): It is a repeating unit constituting the main chain of the conductive polymer; -L 1 - is -(CH2) x1 -、-(CH2) x1 -O-(CH2) y1 -、-(CH2) x1 -O-CO-(CH2) y1 -、-(CH2) x1 -(CH2-CH2-O) y1 -、-(CH2) x1 -O-(CH2-CH2-O) y1 -、-O-(CH2) x1 -(CH2-CH2-O) y1 - and -O-(CH2) x1 -O-(CH2-CH2-O) y1 -, wherein x1 and y1 are integers, and 0≤x1≤20, 0≤y1≤20; -L 2 - is -(CH2) x2 -、-(CH2) x2 -O-, -CO-O-(CH2) x2 -、-O-CO-(CH2) x2 -、-CO-NH-(CH2) x2 -、-C(CH3)2-CO-O-(CH2) x2 、-CH(CH3)-O-(CH2) x2 、-S-CH2-CH2-O-(CH2) x2 and -S-CH2-CH(CH3)-CO-O-(CH2) x2 One or more of , wherein x2 is an integer and 0≤x2≤20; -R 2 for 5. A high performance organic electrochemical transistor biosensor according to claim 4, characterized in that: The monomer unit structure of the bio-coupling group side chain in the biomimetic functional conductive polymer material is shown in formula (II); In formula (II): It is a repeating unit constituting the main chain of the conductive polymer; -L 3 - is -(CH2) x3 -、-(CH2) x3 -O-(CH2) y3 -、-(CH2) x3 -O-CO-(CH2) y3 -、-(CH2) x3 -NH-CO-O-, -(CH2) x3 -(CH2-CH2-O) y3 -、-(CH2) x3 -O-(CH2-CH2-O) y3 -、-O-(CH2) x33 -(CH2-CH2-O) y3 - and -O-(CH2) x3 -O-(CH2-CH2-O) y3 -, wherein x3 and y3 are integers, and 0≤x3≤20, 0≤y3≤20; -L 4 -is -O-, -CO-O-, -O-CH2-CO-O-, -S-(CH2) x4 -CO-O-(CH2) y4 -、-CO-NH-(CH2) x4 -、-NH-(CH2) x4 -、-NH-CO-(CH2) x4 -、-O-CO-(CH2) x4 -、-CO-NH-(CH2) x4 -、 One or more of, wherein x4 and y4 are integers, and 0≤x4≤20, 0≤y4≤20; -R 3 -COOH, -NH2, -O-NH2, -N3, 6. A high performance organic electrochemical transistor biosensor according to claim 5, characterized in that: The monomer unit structure where the ferrocene group side chain is located in the conductive polymer material is shown in formula (III); In formula (I): It is a repeating unit constituting the main chain of the conductive polymer; -L 5 - is -(CH2) x5 -、-(CH2) x5 -O-(CH2) y5 -、-(CH2) x5 -O-CO-(CH2) y5 -、-(CH2) x5 -(CH2-CH2-O) y5 -、-(CH2) x5 -O-(CH2-CH2-O) y5 -、-O-(CH2) x5 -(CH2-CH2-O) y5 - and -O-(CH2) x5 -O-(CH2-CH2-O) y5 -, wherein x5 and y5 are integers, and 0≤x5≤20, 0≤y5≤20; -L 6 - is -(CH2) x6 -、-(CH2) x6 -O-, -CO-O-(CH2) x6 -、-O-CO-(CH2) x6 -、-CO-NH-(CH2) x6 -、-C(CH3)2-CO-O-(CH2) x6 、-CH(CH3)-O-(CH2) x6 、-S-CH2-CH2-O-(CH2) x6 and -S-CH2-CH(CH3)-CO-O-(CH2) x6 One or more of , wherein x6 is an integer and 0≤x6≤20; -R 4 It is ferrocene and its derivatives, catechol and its derivatives or hydroquinone and its derivatives.

7. A high performance organic electrochemical transistor biosensor according to claim 6, characterized in that: and Independently selected from Any one of .

8. The method for preparing a high-performance organic electrochemical transistor biosensor according to any one of claims 1 to 6, characterized in that The steps include: (1) performing photolithographic patterning on the substrate surface, and then depositing the source, drain, gate and connecting lines; (2) After the source electrode, drain electrode, gate electrode and connecting lines are deposited, a package passivation layer is deposited to package the source electrode, drain electrode, gate electrode and connecting lines, and then a window for forming a channel as well as the source electrode, drain electrode and gate electrode are exposed by photolithography and plasma dry etching processes; (3) Spin coating PEDOT:PSS on a window that can form a channel to prepare a channel, modifying the gate with a copolymer conductive polymer material with ferrocene function and biomimetic function, and the gate, source, drain and the channel between the source and drain together constitute a high-performance organic electrochemical transistor biosensor.

9. The method for preparing a high-performance organic electrochemical transistor biosensor according to claim 7, characterized in that: The gate is modified with a ferrocene-functionalized and biomimetic-functionalized copolymer conductive polymer material by an electrochemical polymerization method.

10. The use of a high performance organic electrochemical transistor biosensor according to any one of claims 1 to 5, characterized in that: Used for cell, virus and biomolecule sensing detection.

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