Organic electrochemical transistor sensor for in-situ rapid detection and real-time monitoring of C-reactive protein in complex biological environment

Abstract

The invention relates to a sensor based on an intrinsic antifouling organic electrochemical transistor and preparation and application thereof, the sensor comprises a source electrode, a drain electrode, a grid electrode and a channel arranged between the source electrode and the drain electrode, and the grid electrode is an intrinsic antifouling grid electrode formed by modifying a phosphorylcholine group modified conductive polymer material on the surface of a gold substrate; and the channel is an intrinsic antifouling channel formed by a conductive polymer material modified by a modified phosphorylcholine group, and realizes specific recognition and sensing of C-reactive protein (CRP) under an anti-fouling condition. The prepared product can rapidly detect CRP in a complex biological environment, in-situ detection, real-time monitoring and in-situ detection of the CRP are achieved, and the reliability and practicability of sensing detection of the CRP are remarkably improved.

Description

Technical Field

[0001] The present invention belongs to the technical field of biosensing, and relates to the preparation and application of a sensor of an intrinsically anti-fouling organic electrochemical transistor for detecting C-reactive protein based on a conductive polymer material containing a phosphocholine group. Background Art

[0002] As a core biomarker of acute inflammatory response, C-reactive protein (CRP) has irreplaceable clinical value in infection differentiation, postoperative monitoring, cardiovascular risk assessment and chronic disease management. For example, when infected with bacteria, the CRP level can rapidly increase to 100-500 mg / L, while in viral infection it is usually below 50 mg / L. This characteristic makes it a key basis for quickly differentiating the type of infection in the emergency department. In addition, the early warning ability of high-sensitivity CRP (hs-CRP) to atherosclerosis further expands its application scenarios in the prevention and control of chronic diseases. However, existing detection technologies (such as immunoturbidimetry, enzyme-linked immunosorbent assay technology) rely heavily on laboratory equipment, with a detection time of up to several hours and unable to achieve dynamic monitoring, resulting in limited application in scenarios such as emergency decision-making, real-time early warning during the perioperative period and home health management. Taking postoperative infection monitoring as an example, traditional single detection is difficult to capture the dynamic change trend of CRP, and although existing rapid test strips shorten the detection time, they are difficult to meet the needs of precision medicine due to insufficient sensitivity (especially in the low-concentration range of hs-CRP) and inability to continuously sample. With the development of hierarchical diagnosis and treatment and telemedicine, there is an urgent clinical need for a CRP detection technology with rapid response, high sensitivity, real-time dynamic monitoring ability and portability to support early intervention in infection, personalized medication guidance and long-term health management of high-risk groups. Based on this, developing a new detection platform to break through the bottleneck of existing technologies has become the key breakthrough point for promoting precision diagnosis and proactive health management. In recent years, electrochemical label-free biosensing technology has attracted extensive attention from researchers. It has the characteristics of fast label-free detection, high sensitivity, and in-liquid in-situ detection. At the same time, it also has advantages such as a small sensing core device and automatic quantification and reading of results, which well meet the development requirements of rapid in-situ detection technology for body fluids and have potential application values in multiple health care fields such as community / home health monitoring of major chronic diseases and rapid in-situ detection of individuals during major epidemics.

[0003] Among them, organic electrochemical transistor (OECT) sensors are considered to have the potential to achieve label-free and highly sensitive detection of trace biomarkers, and have gained the favor of researchers due to their low operating voltage level, relatively low manufacturing technology, and compatibility with the aqueous environment. An organic electrochemical transistor is an electronic device based on organic semiconductor materials. Its core structure includes a source electrode, a drain electrode, and a gate electrode. By applying a voltage to the OECT gate, the ion injection in the electrolyte between the source electrode and the drain electrode into the organic semiconductor channel is regulated, causing doping or de-doping effects in the channel material, thereby changing the conductivity of the channel and further changing the magnitude of the current between the source and the drain. A small current change from the gate can achieve a large range of changes in the source-drain current, realizing accurate signal amplification.

[0004] Although OECTs have high signal amplification capabilities, their application in the field of real-time monitoring still faces the following core problems. Traditional OECT sensors mostly rely on multiple scans of the transfer curve to obtain the target concentration information. Frequent voltage switching leads to repeated doping / dedoping of the channel material, accelerating the aging of the channel material and significantly affecting the detection and monitoring stability.

[0005] In addition, existing organic electrochemical transistor (OECT) sensors still face the problem of limited detection rate. To break through this technical bottleneck, Reference 1 (Advanced Materials, 2022, 34(35): 2202972.) proposed a design scheme of integrating the alternating current electrothermal effect (ACET) with OECT. By the action of the alternating electric field, the protein recognition time is shortened to 2 minutes, and the detection time is significantly shortened. However, this technology increases its detection complexity and hinders its point-of-care testing (POCT) application.

[0006] Moreover, the practical application of OECT in in-situ detection of CRP also faces technical bottlenecks. Existing OECT sensors are fabricated using traditional electronic materials without material design optimization for biological applications, and their electrode surfaces do not have the ability to resist interference from complex biological environments. Biomolecules or cells rich in clinical samples are prone to non-specific adhesion to the gate and channel surfaces, generating strong non-specific interference signals and significantly weakening the detection accuracy. Currently, Document 2 (Nature Biomedical Engineering, 2021, 5(7): 666-677.), Document 3 (Science Advances, 2021, 7(38).), Document 4 (Advanced Materials, 2022, 34(35).), and Document 5 (Advanced Materials, 2022, 34(35).) all report that using bovine serum albumin (BSA) to block the gate and channel surfaces can inhibit their non-specific interactions with interferents in complex biological environments. However, BSA blocking usually takes 30 - 60 minutes, significantly increasing the detection time and complexity, and it is difficult to meet the rapid and convenient usage requirements of point-of-care testing; moreover, commercial BSA often contains trace amounts of heterologous proteins or antibody residues, and the OECT sensors blocked by it will respond to specific interferents, affecting the detection accuracy; in addition, the blocking of the gate and channel by BSA will hinder the ion channels, affecting the device performance and reducing the device sensitivity.

[0007] In summary, the existing OECT sensing technology is difficult to meet the requirements of rapid in-situ detection and real-time monitoring of CRP in complex biological environments. Therefore, there is an urgent need to develop a CRP sensing technology based on an intrinsically antifouling organic electrochemical transistor. Summary of the Invention

[0008] The present invention aims to develop a C-reactive protein (CRP) sensing technology based on an intrinsically antifouling organic electrochemical transistor to address the technical problems of existing sensors, such as insufficient real-time monitoring ability, slow detection speed, and inaccurate in-situ detection, and to achieve rapid in-situ detection and real-time monitoring of CRP in complex biological environments, providing an advanced solution for point-of-care testing (POCT) applications.

[0009] To achieve the above object, the technical solution adopted by the present invention is as follows:

[0010] A sensor based on an intrinsically anti-fouling organic electrochemical transistor as described above, comprising a source electrode, a drain electrode, a gate electrode, and a channel disposed between the source electrode and the drain electrode, characterized in that the gate electrode is composed of a modified conductive polymer material with phosphorylcholine groups modified on the surface of a gold electrode to form an intrinsically anti-fouling gate electrode, and the channel is an intrinsically anti-fouling channel modified with a conductive polymer material modified with phosphorylcholine groups, which can achieve rapid detection and real-time monitoring of biomarkers under a constant gate voltage in a complex biological environment.

[0011] A sensor based on an intrinsically anti-fouling organic electrochemical transistor as described above, characterized in that the zwitterionic modified conductive polymer materials modified on the surfaces of the gate electrode and the channel comprise structural units shown in Formula (I) and Formula (II);

[0012]

[0013] Wherein Formula (I) is a conductive polymer material modified with phosphorylcholine groups on the gate electrode, and the number of polymer repeating units is m;

[0014] Formula (II) is a conductive polymer material modified with phosphorylcholine groups on the channel, and the number of polymer repeating units is n;

[0015] In Formula (I) and (II), and are repeating units of the polymer main chain;

[0016] -L1- and -L2- are linking groups between the phosphorylcholine groups and the polymer main chain;

[0017] -R1 is

[0018] and can independently be any one of

[0019] or its derivatives.

[0020] The sensing sensitivity of the intrinsically anti-fouling organic electrochemical transistor sensor to C-reactive protein is greater than 7 μA / dec;

[0021] The detection limit of the intrinsically anti-fouling organic electrochemical transistor sensor to C-reactive protein is not higher than 1 pg / mL;

[0022] During the real-time detection under a constant gate voltage of the intrinsically anti-fouling organic electrochemical transistor sensor, the applied gate voltage is not greater than 0.7 V;

[0023] The non-specific response of the intrinsic anti-fouling organic electrochemical transistor sensor to bovine serum albumin is no greater than 1 μA.

[0024] As a preferred technical solution:

[0025] A sensor based on an intrinsic anti-fouling organic electrochemical transistor as described above, characterized in that

[0026] and can be independently any one of

[0027] The sensing sensitivity of the intrinsic anti-fouling organic electrochemical transistor sensor to C-reactive protein is greater than 10 μA / dec;

[0028] The detection limit of the intrinsic anti-fouling organic electrochemical transistor sensor to C-reactive protein is not higher than 0.5 pg / mL;

[0029] During the real-time detection at a constant gate voltage of the intrinsic anti-fouling organic electrochemical transistor sensor, the applied gate voltage is not greater than 0.5 V;

[0030] The detection time of the intrinsic anti-fouling organic electrochemical transistor to C-reactive protein does not exceed 100 seconds;

[0031] The non-specific response of the intrinsic anti-fouling organic electrochemical transistor sensor to bovine serum albumin is no greater than 0.5 μA.

[0032] As a preferred technical solution:

[0033] A sensor based on an intrinsic anti-fouling organic electrochemical transistor as described above, characterized in that

[0034] and are independently selected from any one of

[0035] The sensing sensitivity of the intrinsic anti-fouling organic electrochemical transistor sensor to C-reactive protein is greater than 13 μA / dec;

[0036] The detection limit of the intrinsic anti-fouling organic electrochemical transistor sensor to C-reactive protein is not higher than 0.11 pg / mL;

[0037] During the real-time detection at a constant gate voltage of the intrinsic anti-fouling organic electrochemical transistor sensor, the applied gate voltage is not greater than 0.4 V;

[0038] The detection time of the intrinsic anti-fouling organic electrochemical transistor to C-reactive protein does not exceed 60 seconds;

[0039] The non-specific response of the intrinsic anti-fouling organic electrochemical transistor sensor to bovine serum albumin is not greater than 0.3 μA.

[0040] A sensor based on an intrinsic anti-fouling organic electrochemical transistor as described above, characterized in that the preparation method of the intrinsic anti-fouling organic electrochemical transistor sensor is: directly modifying a phosphorylcholine group-modified conductive polymer material on the gate and the channel by an electrochemical method or a spin-coating method.

[0041] The intrinsic anti-fouling organic electrochemical transistor sensor as described above is characterized in that it can achieve accurate in-situ rapid detection and real-time monitoring of C-reactive protein in clinical samples.

[0042] Principle of the invention:

[0043] Currently, the OECT detection technology based on the antibody-antigen interaction usually requires multiple scans of the transfer curve to obtain the target concentration. However, the frequent switching of the gate voltage will accelerate the aging of the channel material in the doping / dedoping cycle, resulting in a decrease in the stability of the sensor. Through experimental research, it is found that the phosphorylcholine-modified conductive polymer material has a porous structure, and its high specific surface area characteristics can significantly enhance its interaction with CRP. At the same time, the experimental results show that compared with the traditional antigen-antibody binding mechanism, after using the phosphorylcholine-modified conductive polymer material to modify the gate and the channel, the specific interaction between CRP and the gate and channel electrodes can be more significantly enhanced, thereby significantly changing the electrochemical properties of the gate and the channel. Moreover, the high dielectric characteristics of the zwitterionic-modified conductive polymer are also beneficial to the further expansion of the double layer on the gate surface, strengthening the perturbation of CRP on the gate double layer and enhancing the sensing response. In addition, the combined effect of the constant voltage applied on the gate and the channel and the conductive characteristics of the phosphorylcholine-modified conductive polymer may also enhance the specific binding of CRP to the functionalized interface, thereby enhancing the signal response intensity of the sensor. It is precisely due to the combined action of the above factors that the highly sensitive detection of CRP can be achieved under the condition of a constant potential.

[0044] At the same time, the present invention constructs a water-like microenvironment on the surfaces of the gate and the channel by using a phosphorylcholine group-modified conductive polymer material, which may promote and accelerate the specific binding of C-reactive protein (CRP) on the surfaces of the gate and the channel. At the same time, as described above, under the condition of synchronously applying a constant voltage to the gate and the channel, this electric field may also further enhance the specific interaction between CRP and the functionalized interface, which is more conducive to the rapid binding of CRP to the gate and the channel compared with the variable gate voltage detection condition. The above two mechanisms work together, thus facilitating the rapid response of the OECT sensor to CRP.

[0045] In addition, the experimental results show that after introducing phosphorylcholine groups to modify the conductive polymer material on the gate and channel surfaces, compared with conventional electrode materials, even under the condition of applying a specific voltage, it still exhibits the anti-adsorption characteristics of a quasi-neutral surface, can effectively inhibit the non-specific binding of positively or negatively charged proteins, and significantly improves the ability of the OECT sensor to resist interference from complex biological environments under a constant voltage. Considering that a relatively high applied voltage may also affect the sensor performance, we systematically explored the influence of the gate and channel voltages on the anti-interference performance and determined the optimal operating voltage range of the device. Further interference verification was carried out using positively charged bovine serum albumin (BSA) and fibrinogen, negatively charged lysozyme, and complex biological matrices such as fetal bovine serum (FBS). The results show that the OECT sensor can still achieve in-situ detection and real-time monitoring of CRP without blocking treatment, demonstrating excellent selectivity and biocompatibility.

[0046] In summary, in view of the technical problems of the existing sensors, such as difficult real-time monitoring, insufficient detection speed, and inaccurate in-situ detection, the present invention develops a CRP sensing technology based on an intrinsically anti-fouling organic electrochemical transistor, which can achieve rapid detection, real-time monitoring, and in-situ detection of CRP in a complex biological environment, and has high reliability, high sensitivity, and clinical practicability, providing an innovative solution for point-of-care testing (POCT) applications.

[0047] Beneficial effects:

[0048] (1) The sensor based on an intrinsically anti-fouling organic electrochemical transistor of the present invention can sensitively and specifically detect CRP at a low constant voltage, achieve stable real-time monitoring of CRP at a constant voltage, and avoid the problems of easy aging of the channel material and unstable detection caused by traditional transfer curve testing.

[0049] (2) The sensor based on an intrinsically anti-fouling organic electrochemical transistor of the present invention significantly improves the detection speed and realizes the rapid detection of CRP by modifying the conductive polymer material with phosphorylcholine groups on the gate and channel surfaces of the organic electrochemical transistor.

[0050] (3) The present invention provides a sensor based on an intrinsically anti-fouling organic electrochemical transistor. The phosphorylcholine group-modified conductive polymer material used still maintains excellent non-specific protein adsorption resistance within a specific voltage range, enabling the device to have excellent anti-interference performance against complex biological environments under constant voltage detection conditions. Description of the Drawings

[0051] Figure 1Transfer curves of a sensor based on an organic electrochemical transistor with an unfunctionalized gate and channel (left figure) and a sensor based on an intrinsic antifouling organic electrochemical transistor with both functionalized gate and channel (right figure) before and after BSA treatment (i.e., before and after soaking in an aqueous BSA solution for 30 minutes);

[0052] Figure 2 Transconductance curves of a sensor based on an organic electrochemical transistor with an unfunctionalized gate and channel (left figure) and a sensor based on an intrinsic antifouling organic electrochemical transistor with both functionalized gate and channel (right figure) before and after BSA treatment (i.e., before and after soaking in an aqueous BSA solution for 30 minutes);

[0053] Figure 3 Real-time detection of CRP by a sensor based on an intrinsic antifouling organic electrochemical transistor with both functionalized gate and channel, where the CRP concentration range in HEPES (Ga 2+ ) is from 1 to 10 6 Relationship curve between the channel current response and CRP concentration.

[0054] Figure 4 Real-time channel current response of a sensor based on an intrinsic antifouling organic electrochemical transistor with both functionalized gate and channel to the continuous addition of buffer, bovine serum albumin, fibrinogen, fetal bovine serum, lysozyme, and C-reactive protein. Detailed implementation manners

[0055] The present invention will be further described below in conjunction with the detailed implementation manners. It should be understood that these embodiments are only used to illustrate the present invention and not 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 also fall within the scope defined by the appended claims of this application.

[0056] The test methods involved in the embodiments are as follows:

[0057] Transfer curve: A sensor based on an intrinsic antifouling organic electrochemical transistor is tested using a Keithley 2636B dual-channel source meter; the performance characterization is carried out in a PBS solution with a pH of 7.4; the gate voltage ranges from -0.4 V to 0.8 V, and the source-drain voltage is -0.4 V.

[0058] Example 1

[0059] A preparation method of a sensor based on an intrinsic antifouling organic electrochemical transistor, the specific steps are as follows:

[0060] (1) An intrinsic antifouling channel is prepared by electrochemically polymerizing a phosphorylcholine group-modified conductive polymer material on the channel, with Using [monomer] as the monomer, with the channel as the working electrode, a platinum mesh as the counter electrode, and Ag / Ag⁺ as the reference electrode, cyclic voltammetry was applied for polymerization. The scanning range was -0.6 to 1.02 V, and the scanning speed was 100 mV / s to obtain a channel modified with a phosphorylcholine group-modified conductive polymer material.

[0061] (2) A spin-coating method was used to coat a layer of phosphorylcholine group-modified conductive polymer material with a thickness of 10 nm on the gate to prepare an intrinsic anti-fouling gate.

[0062] (3) The intrinsic anti-fouling gate modified with the phosphorylcholine group-modified conductive polymer material and the intrinsic anti-fouling channel together form a sensor based on an intrinsic anti-fouling organic electrochemical transistor.

[0063] The sensitivity of the sensor based on the intrinsic anti-fouling organic electrochemical transistor to C-reactive protein is 13.8 μA / dec; the detection time of the sensor based on the intrinsic anti-fouling organic electrochemical transistor to C-reactive protein is 56 s; the detection limit (LOD) of the sensor based on the intrinsic anti-fouling organic electrochemical transistor to C-reactive protein is 0.102 pg / mL.

[0064] Example 2

[0065] A preparation method of a sensor based on an intrinsic anti-fouling organic electrochemical transistor is as follows:

[0066] (1) A spin-coating method was used to coat a layer of phosphorylcholine group-modified conductive polymer material with a thickness of 10 nm on the channel to prepare an intrinsic anti-fouling channel.

[0067] (2) An electrochemical polymerization method was used to modify the phosphorylcholine group-modified conductive polymer material on the gate to prepare an intrinsic anti-fouling gate. Using as the monomer, with the gate as the working electrode, a platinum mesh as the counter electrode, and Ag / Ag⁺ as the reference electrode, cyclic voltammetry was applied for polymerization. The scanning range was -0.6 to 1.1 V, and the scanning speed was 100 mV / s to obtain a gate modified with the phosphorylcholine group-modified conductive polymer material.

[0068] (3) The intrinsic anti-fouling gate modified with the phosphorylcholine group-modified conductive polymer material and the intrinsic anti-fouling channel together form a sensor based on an intrinsic anti-fouling organic electrochemical transistor.

[0069] The sensitivity of the sensor based on the intrinsic anti-fouling organic electrochemical transistor to C-reactive protein is 13.7 μA / dec; the detection time of the sensor based on the intrinsic anti-fouling organic electrochemical transistor to C-reactive protein is 53 s; the detection limit (LOD) of the sensor based on the intrinsic anti-fouling organic electrochemical transistor to C-reactive protein is 0.11 pg / mL.

[0070] Example 3

[0071] A preparation method of a sensor based on an intrinsically anti-fouling organic electrochemical transistor is as follows:

[0072] (1) Prepare an intrinsically anti-fouling channel by modifying a conductive polymer material modified with choline phosphate groups on the channel using an electrochemical polymerization method. Using as a monomer, using the channel as the working electrode, a platinum mesh as the counter electrode, and Ag / Ag⁺ as the reference electrode, apply cyclic voltammetry for polymerization with a scanning range of -0.6 to 1.02 V and a scanning speed of 100 mV / s to obtain a channel modified with a conductive polymer material modified with choline phosphate groups;

[0073] (2) Prepare an intrinsically anti-fouling gate by modifying a conductive polymer material modified with choline phosphate groups on the gate using an electrochemical polymerization method. Using as a monomer, using the gate as the working electrode, a platinum mesh as the counter electrode, and Ag / Ag⁺ as the reference electrode, apply cyclic voltammetry for polymerization with a scanning range of -0.6 to 1.1 V and a scanning speed of 100 mV / s to obtain a gate modified with a conductive polymer material modified with choline phosphate groups;

[0074] (3) The intrinsically anti-fouling gate modified with a conductive polymer material modified with choline phosphate groups and the intrinsically anti-fouling channel together form a sensor based on an intrinsically anti-fouling organic electrochemical transistor.

[0075] The sensitivity of the sensor based on an intrinsically anti-fouling organic electrochemical transistor to C-reactive protein is 13.5 μA / dec; the detection time of the sensor based on an intrinsically anti-fouling organic electrochemical transistor to C-reactive protein is 52 seconds; the detection limit (LOD) of the sensor based on an intrinsically anti-fouling organic electrochemical transistor to C-reactive protein is 0.108 pg / mL.

[0076] Example 4

[0077] A preparation method of a sensor based on an intrinsically anti-fouling organic electrochemical transistor is as follows:

[0078] (1) Prepare an intrinsically anti-fouling channel by modifying a conductive polymer material modified with choline phosphate groups on the channel using an electrochemical polymerization method. Using as a monomer, using the channel as the working electrode, a platinum mesh as the counter electrode, and Ag / Ag⁺ as the reference electrode, apply cyclic voltammetry for polymerization with a scanning range of -0.6 to 1.025 V and a scanning speed of 100 mV / s to obtain a channel modified with a conductive polymer material modified with choline phosphate groups;

[0079] (2) Prepare an intrinsically anti-fouling gate by spin-coating a layer of a conductive polymer material modified with choline phosphate groups with a thickness of 10 nm on the gate;

[0080] (3) The intrinsic anti-fouling gate and the intrinsic anti-fouling channel modified with phosphocholine group modified conductive polymer materials together constitute a sensor based on the intrinsic anti-fouling organic electrochemical transistor.

[0081] The sensitivity of the sensor based on the intrinsic anti-fouling organic electrochemical transistor to C-reactive protein is 13.9 μA / dec; the detection time of the sensor based on the intrinsic anti-fouling organic electrochemical transistor to C-reactive protein is 55 s; the detection limit (LOD) of the sensor based on the intrinsic anti-fouling organic electrochemical transistor to C-reactive protein is 0.105 pg / mL.

[0082] Example 5

[0083] A preparation method of a sensor based on an intrinsic anti-fouling organic electrochemical transistor, the specific steps are as follows:

[0084] (1) A layer of phosphocholine group modified conductive polymer material with a thickness of 10 nm is spin-coated on the channel to prepare an intrinsic anti-fouling channel;

[0085] (2) The intrinsic anti-fouling gate is prepared by electrochemically polymerizing the phosphocholine group modified conductive polymer material on the gate. Using as the monomer, the gate as the working electrode, the platinum mesh as the counter electrode, and Ag / Ag⁺ as the reference electrode, cyclic voltammetry is applied for polymerization, the scanning range is -0.6 to 1.13 V, and the scanning speed is 100 mV / s to obtain a gate modified with phosphocholine group modified conductive polymer material;

[0086] (3) The intrinsic anti-fouling gate and the intrinsic anti-fouling channel modified with phosphocholine group modified conductive polymer materials together constitute a sensor based on the intrinsic anti-fouling organic electrochemical transistor.

[0087] The sensitivity of the sensor based on the intrinsic anti-fouling organic electrochemical transistor to C-reactive protein is 13.8 μA / dec; the detection time of the sensor based on the intrinsic anti-fouling organic electrochemical transistor to C-reactive protein is 53 s; the detection limit (LOD) of the sensor based on the intrinsic anti-fouling organic electrochemical transistor to C-reactive protein is 0.11 pg / mL.

[0088] Example 6

[0089] A preparation method of a sensor based on an intrinsic anti-fouling organic electrochemical transistor, the specific steps are as follows:

[0090] (1) The intrinsic anti-fouling channel is prepared by electrochemically polymerizing the phosphocholine group modified conductive polymer material on the channel. Using Using [monomer] as the monomer, with the channel as the working electrode, a platinum mesh as the counter electrode, and Ag / Ag+ as the reference electrode, cyclic voltammetry was applied for polymerization. The scanning range was -0.6 to 1.025 V, and the scanning speed was 100 mV / s to obtain a channel modified with a phosphorylcholine group-modified conductive polymer material;

[0091] (2) An intrinsic anti-fouling gate was prepared by electrochemically polymerizing a phosphorylcholine group-modified conductive polymer material on the gate. Using as the monomer, with the gate as the working electrode, a platinum mesh as the counter electrode, and Ag / Ag+ as the reference electrode, cyclic voltammetry was applied for polymerization. The scanning range was -0.6 to 1.13 V, and the scanning speed was 100 mV / s to obtain a gate modified with a phosphorylcholine group-modified conductive polymer material;

[0092] (3) The intrinsic anti-fouling gate modified with a phosphorylcholine group-modified conductive polymer material and the intrinsic anti-fouling channel together form a sensor based on an intrinsic anti-fouling organic electrochemical transistor.

[0093] The sensitivity of the sensor based on the intrinsic anti-fouling organic electrochemical transistor to C-reactive protein is 14.1 μA / dec; the detection time of the sensor based on the intrinsic anti-fouling organic electrochemical transistor to C-reactive protein is 52 seconds; the detection limit (LOD) of the sensor based on the intrinsic anti-fouling organic electrochemical transistor to C-reactive protein is 0.11 pg / mL.

[0094] Example 7

[0095] A method for preparing a sensor based on an intrinsic anti-fouling organic electrochemical transistor, the specific steps are as follows:

[0096] (1) A layer of phosphorylcholine group-modified conductive polymer material with a thickness of 10 nm was spin-coated on the channel to prepare an intrinsic anti-fouling channel;

[0097] (2) A layer of phosphorylcholine group-modified conductive polymer material with a thickness of 10 nm was spin-coated on the gate to prepare an intrinsic anti-fouling gate;

[0098] (3) The intrinsic anti-fouling gate modified with a phosphorylcholine group-modified conductive polymer material and the intrinsic anti-fouling channel together form a sensor based on an intrinsic anti-fouling organic electrochemical transistor.

[0099] The sensitivity of the sensor based on the intrinsic anti-fouling organic electrochemical transistor to C-reactive protein is 13.7 μA / dec; the detection time of the sensor based on the intrinsic anti-fouling organic electrochemical transistor to C-reactive protein is 60 seconds; the detection limit (LOD) of the sensor based on the intrinsic anti-fouling organic electrochemical transistor to C-reactive protein is 0.1 pg / mL.

[0100] Example 8

[0101] A preparation method of a sensor based on an intrinsically anti-fouling organic electrochemical transistor is as follows:

[0102] (1) Modify the conductive polymer material modified with choline phosphate groups on the channel by electrochemical polymerization to prepare an intrinsically anti-fouling channel. Using as the monomer, using the channel as the working electrode, a platinum mesh as the counter electrode, and Ag / Ag+ as the reference electrode, apply cyclic voltammetry for polymerization. The scanning range is -0.6 to 1.03 V, and the scanning speed is 100 mV / s to obtain a channel modified with a conductive polymer material modified with choline phosphate groups;

[0103] (2) Modify the conductive polymer material modified with choline phosphate groups on the gate by electrochemical polymerization to prepare an intrinsically anti-fouling gate. Using as the monomer, using the gate as the working electrode, a platinum mesh as the counter electrode, and Ag / Ag+ as the reference electrode, apply cyclic voltammetry for polymerization. The scanning range is -0.6 to 1.14 V, and the scanning speed is 100 mV / s to obtain a gate modified with a conductive polymer material modified with choline phosphate groups;

[0104] (3) The intrinsically anti-fouling gate modified with a conductive polymer material modified with choline phosphate groups and the intrinsically anti-fouling channel together form a sensor based on an intrinsically anti-fouling organic electrochemical transistor.

[0105] The sensitivity of the sensor based on the intrinsically anti-fouling organic electrochemical transistor to C-reactive protein is 13.6 μA / dec; the detection time of the sensor based on the intrinsically anti-fouling organic electrochemical transistor to C-reactive protein is 55 seconds; the detection limit (LOD) of the sensor based on the intrinsically anti-fouling organic electrochemical transistor to C-reactive protein is 0.108 pg / mL.

[0106] Example 9

[0107] A preparation method of a sensor based on an intrinsically anti-fouling organic electrochemical transistor is as follows:

[0108] (1) Modify the conductive polymer material modified with choline phosphate groups on the channel by electrochemical polymerization to prepare an intrinsically anti-fouling channel. Using as the monomer, using the channel as the working electrode, a platinum mesh as the counter electrode, and Ag / Ag+ as the reference electrode, apply cyclic voltammetry for polymerization. The scanning range is -0.6 to 1.03 V, and the scanning speed is 100 mV / s to obtain a channel modified with a conductive polymer material modified with choline phosphate groups;

[0109] (2) Spin-coat a layer of conductive polymer material modified with choline phosphate groups with a thickness of 10 nm on the gate to prepare an intrinsically anti-fouling gate;

[0110] (3) The intrinsic anti-fouling gate electrode and the intrinsic anti-fouling channel modified with phosphocholine group modified conductive polymer materials together constitute a sensor based on an intrinsic anti-fouling organic electrochemical transistor.

[0111] The sensitivity of the sensor based on the intrinsic anti-fouling organic electrochemical transistor to C-reactive protein is 13.5 μA / dec; the detection time of the sensor based on the intrinsic anti-fouling organic electrochemical transistor to C-reactive protein is 56 s; the detection limit (LOD) of the sensor based on the intrinsic anti-fouling organic electrochemical transistor to C-reactive protein is 0.107 pg / mL.

[0112] Example 10

[0113] A preparation method of a sensor based on an intrinsic anti-fouling organic electrochemical transistor, the specific steps are as follows:

[0114] (1) Spin-coat a layer of phosphocholine group modified conductive polymer material with a thickness of 10 nm on the channel to prepare an intrinsic anti-fouling channel;

[0115] (2) Electrochemically polymerize to modify the phosphocholine group modified conductive polymer material on the gate electrode to prepare an intrinsic anti-fouling gate electrode, using as the monomer, the gate electrode as the working electrode, a platinum mesh as the counter electrode, and Ag / Ag⁺ as the reference electrode, and apply cyclic voltammetry for polymerization. The scanning range is -0.6 to 1.14 V, and the scanning speed is 100 mV / s to obtain a gate electrode modified with a phosphocholine group modified conductive polymer material;

[0116] (3) The intrinsic anti-fouling gate electrode and the intrinsic anti-fouling channel modified with phosphocholine group modified conductive polymer materials together constitute a sensor based on an intrinsic anti-fouling organic electrochemical transistor.

[0117] The sensitivity of the sensor based on the intrinsic anti-fouling organic electrochemical transistor to C-reactive protein is 13.4 μA / dec; the detection time of the sensor based on the intrinsic anti-fouling organic electrochemical transistor to C-reactive protein is 57 s; the detection limit (LOD) of the sensor based on the intrinsic anti-fouling organic electrochemical transistor to C-reactive protein is 0.106 pg / mL.

[0118] Example 11

[0119] A preparation method of a sensor based on an intrinsic anti-fouling organic electrochemical transistor, the specific steps are as follows:

[0120] (1) Electrochemically polymerize to modify the phosphocholine group modified conductive polymer material on the channel to prepare an intrinsic anti-fouling channel, using Using [monomer] as the monomer, with the channel as the working electrode, a platinum mesh as the counter electrode, and Ag / Ag⁺ as the reference electrode, cyclic voltammetry was applied for polymerization. The scanning range was -0.6 to 1.04 V, and the scanning speed was 100 mV / s, to obtain a channel modified with a phosphorylcholine group-modified conductive polymer material;

[0121] (2) An intrinsic anti-fouling gate was prepared by electrochemically polymerizing a phosphorylcholine group-modified conductive polymer material on the gate. Using as the monomer, with the gate as the working electrode, a platinum mesh as the counter electrode, and Ag / Ag⁺ as the reference electrode, cyclic voltammetry was applied for polymerization. The scanning range was -0.6 to 1.15 V, and the scanning speed was 100 mV / s, to obtain a gate modified with a phosphorylcholine group-modified conductive polymer material;

[0122] (3) The intrinsic anti-fouling gate modified with a phosphorylcholine group-modified conductive polymer material and the intrinsic anti-fouling channel together form a sensor based on an intrinsic anti-fouling organic electrochemical transistor.

[0123] The sensitivity of the sensor based on the intrinsic anti-fouling organic electrochemical transistor to C-reactive protein is 13.2 μA / dec; the detection time of the sensor based on the intrinsic anti-fouling organic electrochemical transistor for C-reactive protein is 57 seconds; the detection limit (LOD) of the sensor based on the intrinsic anti-fouling organic electrochemical transistor for C-reactive protein is 0.105 pg / mL.

[0124] Example 12

[0125] A preparation method of a sensor based on an intrinsic anti-fouling organic electrochemical transistor, the specific steps are as follows:

[0126] (1) A layer of phosphorylcholine group-modified conductive polymer material with a thickness of 10 nm was spin-coated on the channel to prepare an intrinsic anti-fouling channel;

[0127] (2) An intrinsic anti-fouling gate was prepared by electrochemically polymerizing a phosphorylcholine group-modified conductive polymer material on the gate. Using as the monomer, with the gate as the working electrode, a platinum mesh as the counter electrode, and Ag / Ag⁺ as the reference electrode, cyclic voltammetry was applied for polymerization. The scanning range was -0.6 to 1.15 V, and the scanning speed was 100 mV / s, to obtain a gate modified with a phosphorylcholine group-modified conductive polymer material;

[0128] (3) The intrinsic anti-fouling gate modified with a phosphorylcholine group-modified conductive polymer material and the intrinsic anti-fouling channel together form a sensor based on an intrinsic anti-fouling organic electrochemical transistor.

[0129] The sensitivity of the sensor based on the intrinsically anti-fouling organic electrochemical transistor to C-reactive protein is 13.3 μA / dec; the detection time of the sensor based on the intrinsically anti-fouling organic electrochemical transistor to C-reactive protein is 56 s; the detection limit (LOD) of the sensor based on the intrinsically anti-fouling organic electrochemical transistor to C-reactive protein is 0.106 pg / mL.

[0130] Example 13

[0131] A preparation method of a sensor based on an intrinsically anti-fouling organic electrochemical transistor is as follows:

[0132] (1) An intrinsically anti-fouling channel is prepared by electrochemically polymerizing a phosphocholine group-modified conductive polymer material on the channel. Using as a monomer, using the channel as the working electrode, a platinum mesh as the counter electrode, and Ag / Ag⁺ as the reference electrode, applying cyclic voltammetry for polymerization, with a scanning range of -0.6 to 1.04 V and a scanning speed of 100 mV / s, to obtain a channel modified with a phosphocholine group-modified conductive polymer material;

[0133] (2) A layer of phosphocholine group-modified conductive polymer material with a thickness of 10 nm is spin-coated on the gate to prepare an intrinsically anti-fouling gate;

[0134] (3) The intrinsically anti-fouling gate modified with a phosphocholine group-modified conductive polymer material and the intrinsically anti-fouling channel together form a sensor based on an intrinsically anti-fouling organic electrochemical transistor.

[0135] The sensitivity of the sensor based on the intrinsically anti-fouling organic electrochemical transistor to C-reactive protein is 13.1 μA / dec; the detection time of the sensor based on the intrinsically anti-fouling organic electrochemical transistor to C-reactive protein is 59 s; the detection limit (LOD) of the sensor based on the intrinsically anti-fouling organic electrochemical transistor to C-reactive protein is 0.109 pg / mL.

[0136] Example 14

[0137] A preparation method of a sensor based on an intrinsically anti-fouling organic electrochemical transistor is as follows:

[0138] (1) An intrinsically anti-fouling channel is prepared by electrochemically polymerizing a phosphocholine group-modified conductive polymer material on the channel. Using as a monomer, using the channel as the working electrode, a platinum mesh as the counter electrode, and Ag / Ag⁺ as the reference electrode, applying cyclic voltammetry for polymerization, with a scanning range of -0.6 to 1.05 V and a scanning speed of 100 mV / s, to obtain a channel modified with a phosphocholine group-modified conductive polymer material;

[0139] (2) The intrinsic anti-fouling gate is prepared by modifying the conductive polymer material with choline phosphate groups on the gate using an electrochemical polymerization method. Using as the monomer, with the gate as the working electrode, a platinum mesh as the counter electrode, and Ag / Ag+ as the reference electrode, cyclic voltammetry is applied for polymerization. The scanning range is -0.6 to 1.16 V, and the scanning speed is 100 mV / s, to obtain a gate modified with a choline phosphate group-modified conductive polymer material;

[0140] (3) The intrinsic anti-fouling gate modified with a choline phosphate group-modified conductive polymer material and the intrinsic anti-fouling channel together form a sensor based on an intrinsic anti-fouling organic electrochemical transistor.

[0141] The sensitivity of the sensor based on the intrinsic anti-fouling organic electrochemical transistor to C-reactive protein is 13.4 μA / dec; the detection time of the sensor based on the intrinsic anti-fouling organic electrochemical transistor to C-reactive protein is 60 seconds; the detection limit (LOD) of the sensor based on the intrinsic anti-fouling organic electrochemical transistor to C-reactive protein is 0.103 pg / mL.

[0142] Example 15

[0143] A preparation method of a sensor based on an intrinsic anti-fouling organic electrochemical transistor, the specific steps are as follows:

[0144] (1) The intrinsic anti-fouling channel is prepared by modifying the conductive polymer material with choline phosphate groups on the channel using an electrochemical polymerization method. Using as the monomer, with the channel as the working electrode, a platinum mesh as the counter electrode, and Ag / Ag+ as the reference electrode, cyclic voltammetry is applied for polymerization. The scanning range is -0.6 to 1.05 V, and the scanning speed is 100 mV / s, to obtain a channel modified with a choline phosphate group-modified conductive polymer material;

[0145] (2) A layer of choline phosphate group-modified conductive polymer material with a thickness of 10 nm is spin-coated on the gate to prepare an intrinsic anti-fouling gate;

[0146] (3) The intrinsic anti-fouling gate modified with a choline phosphate group-modified conductive polymer material and the intrinsic anti-fouling channel together form a sensor based on an intrinsic anti-fouling organic electrochemical transistor.

[0147] The sensitivity of the sensor based on the intrinsic anti-fouling organic electrochemical transistor to C-reactive protein is 13.3 μA / dec; the detection time of the sensor based on the intrinsic anti-fouling organic electrochemical transistor to C-reactive protein is 58 seconds; the detection limit (LOD) of the sensor based on the intrinsic anti-fouling organic electrochemical transistor to C-reactive protein is 0.106 pg / mL.

[0148] Example 16

[0149] A preparation method of a sensor based on an intrinsically anti-fouling organic electrochemical transistor is as follows:

[0150] (1) A layer of 10 nm thick choline phosphate group modified conductive polymer material is coated on the channel by spin coating to prepare an intrinsically anti-fouling channel;

[0151] (2) The intrinsically anti-fouling gate is prepared by electrochemically polymerizing the choline phosphate group modified conductive polymer material on the gate. Using as the monomer, the gate as the working electrode, the platinum net as the counter electrode, and Ag / Ag+ as the reference electrode, cyclic voltammetry is applied for polymerization. The scanning range is -0.6 to 1.16 V, and the scanning speed is 100 mV / s to obtain a gate modified with choline phosphate group modified conductive polymer material;

[0152] (3) The intrinsically anti-fouling gate modified with choline phosphate group modified conductive polymer material and the intrinsically anti-fouling channel together form a sensor based on an intrinsically anti-fouling organic electrochemical transistor.

[0153] The sensitivity of the sensor based on the intrinsically anti-fouling organic electrochemical transistor to C-reactive protein is 13.5 μA / dec; the detection time of the sensor based on the intrinsically anti-fouling organic electrochemical transistor to C-reactive protein is 59 seconds; the detection limit (LOD) of the sensor based on the intrinsically anti-fouling organic electrochemical transistor to C-reactive protein is 0.105 pg / mL.

[0154] Example 17

[0155] A preparation method of a sensor based on an intrinsically anti-fouling organic electrochemical transistor is as follows:

[0156] (1) The intrinsically anti-fouling channel is prepared by electrochemically polymerizing the choline phosphate group modified conductive polymer material on the channel. Using as the monomer, the channel as the working electrode, the platinum net as the counter electrode, and Ag / Ag+ as the reference electrode, cyclic voltammetry is applied for polymerization. The scanning range is -0.6 to 1.05 V, and the scanning speed is 100 mV / s to obtain a channel modified with choline phosphate group modified conductive polymer material;

[0157] (2) The intrinsically anti-fouling gate is prepared by electrochemically polymerizing the choline phosphate group modified conductive polymer material on the gate. Using as the monomer, the gate as the working electrode, the platinum net as the counter electrode, and Ag / Ag+ as the reference electrode, cyclic voltammetry is applied for polymerization. The scanning range is -0.6 to 1.16 V, and the scanning speed is 100 mV / s to obtain a gate modified with choline phosphate group modified conductive polymer material;

[0158] (3) The sensor based on the intrinsically anti-fouling organic electrochemical transistor is composed of an intrinsically anti-fouling gate electrode modified with a phosphocholine group-modified conductive polymer material and an intrinsically anti-fouling channel.

[0159] The sensitivity of the sensor based on the intrinsically anti-fouling organic electrochemical transistor to C-reactive protein is 13.6 μA / dec; the detection time of the sensor based on the intrinsically anti-fouling organic electrochemical transistor for C-reactive protein is 60 seconds; the detection limit (LOD) of the sensor based on the intrinsically anti-fouling organic electrochemical transistor for C-reactive protein is 0.102 pg / mL.

[0160] Example 18

[0161] A preparation method of a sensor based on an intrinsically anti-fouling organic electrochemical transistor, the specific steps are as follows:

[0162] (1) An intrinsically anti-fouling channel is prepared by electrochemically polymerizing a phosphocholine group-modified conductive polymer material on the channel. Using as the monomer, the channel as the working electrode, a platinum mesh as the counter electrode, and Ag / Ag+ as the reference electrode, cyclic voltammetry is applied for polymerization, the scanning range is -0.6 to 1.05 V, and the scanning speed is 100 mV / s to obtain a channel modified with a phosphocholine group-modified conductive polymer material;

[0163] (2) A layer of phosphocholine group-modified conductive polymer material with a thickness of 10 nm is spin-coated on the gate electrode to prepare an intrinsically anti-fouling gate electrode;

[0164] (3) The sensor based on the intrinsically anti-fouling organic electrochemical transistor is composed of an intrinsically anti-fouling gate electrode modified with a phosphocholine group-modified conductive polymer material and an intrinsically anti-fouling channel.

[0165] The sensitivity of the sensor based on the intrinsically anti-fouling organic electrochemical transistor to C-reactive protein is 13.3 μA / dec; the detection time of the sensor based on the intrinsically anti-fouling organic electrochemical transistor for C-reactive protein is 58 seconds; the detection limit (LOD) of the sensor based on the intrinsically anti-fouling organic electrochemical transistor for C-reactive protein is 0.104 pg / mL.

[0166] Example 19

[0167] A preparation method of a sensor based on an intrinsically anti-fouling organic electrochemical transistor, the specific steps are as follows:

[0168] (1) An intrinsically anti-fouling channel is prepared by spin-coating a layer of phosphocholine group-modified conductive polymer material with a thickness of 10 nm on the channel;

[0169] (2) The intrinsic anti-fouling gate is prepared by electrochemically polymerizing a conductive polymer material modified with choline phosphate groups on the gate. Using as the monomer, the gate as the working electrode, a platinum mesh as the counter electrode, and Ag / Ag+ as the reference electrode, cyclic voltammetry is applied for polymerization with a scanning range of -0.6 to 1.16 V and a scanning speed of 100 mV / s to obtain a gate modified with a conductive polymer material modified with choline phosphate groups;

[0170] (3) The intrinsic anti-fouling gate modified with a conductive polymer material modified with choline phosphate groups and the intrinsic anti-fouling channel together form a sensor based on an intrinsic anti-fouling organic electrochemical transistor.

[0171] The sensitivity of the sensor based on the intrinsic anti-fouling organic electrochemical transistor to C-reactive protein is 13.5 μA / dec; the detection time of the sensor based on the intrinsic anti-fouling organic electrochemical transistor to C-reactive protein is 59 seconds; the detection limit (LOD) of the sensor based on the intrinsic anti-fouling organic electrochemical transistor to C-reactive protein is 0.108 pg / mL.

[0172] Example 20

[0173] A preparation method of a sensor based on an intrinsic anti-fouling organic electrochemical transistor, the specific steps are as follows:

[0174] (1) The intrinsic anti-fouling channel is prepared by electrochemically polymerizing a conductive polymer material containing choline phosphate groups on the channel. Using as the monomer, the channel as the working electrode, a platinum mesh as the counter electrode, and Ag / Ag+ as the reference electrode, cyclic voltammetry is applied for polymerization with a scanning range of -0.6 to 1.06 V and a scanning speed of 100 mV / s to obtain a channel modified with a conductive polymer material modified with choline phosphate groups;

[0175] (2) The intrinsic anti-fouling gate is prepared by electrochemically polymerizing a conductive polymer material modified with choline phosphate groups on the gate. Using as the monomer, the gate as the working electrode, a platinum mesh as the counter electrode, and Ag / Ag+ as the reference electrode, cyclic voltammetry is applied for polymerization with a scanning range of -0.6 to 1.17 V and a scanning speed of 100 mV / s to obtain a gate modified with a conductive polymer material modified with choline phosphate groups;

[0176] (3) The intrinsic anti-fouling gate modified with a conductive polymer material modified with choline phosphate groups and the intrinsic anti-fouling channel together form a sensor based on an intrinsic anti-fouling organic electrochemical transistor.

[0177] The sensitivity of the sensor based on the intrinsically anti-fouling organic electrochemical transistor to C-reactive protein is 13 μA / dec; the detection time of the sensor based on the intrinsically anti-fouling organic electrochemical transistor to C-reactive protein is 55 s; the detection limit (LOD) of the sensor based on the intrinsically anti-fouling organic electrochemical transistor to C-reactive protein is 0.103 pg / mL.

[0178] Example 21

[0179] A preparation method of a sensor based on an intrinsically anti-fouling organic electrochemical transistor is as follows:

[0180] (1) A layer of 10 nm thick choline phosphate group modified conductive polymer material is coated on the channel by spin coating to prepare an intrinsically anti-fouling channel;

[0181] (2) The choline phosphate group modified conductive polymer material is used to modify the gate by electrochemical polymerization to prepare an intrinsically anti-fouling gate. Using as the monomer, the gate as the working electrode, a platinum mesh as the counter electrode, and Ag / Ag⁺ as the reference electrode, cyclic voltammetry is applied for polymerization with a scanning range of -0.6 to 1.17 V and a scanning speed of 100 mV / s to obtain a gate modified with choline phosphate group modified conductive polymer material;

[0182] (3) The intrinsically anti-fouling gate modified with choline phosphate group modified conductive polymer material and the intrinsically anti-fouling channel together form a sensor based on an intrinsically anti-fouling organic electrochemical transistor.

[0183] The sensitivity of the sensor based on the intrinsically anti-fouling organic electrochemical transistor to C-reactive protein is 13.2 μA / dec; the detection time of the sensor based on the intrinsically anti-fouling organic electrochemical transistor to C-reactive protein is 57 s; the detection limit (LOD) of the sensor based on the intrinsically anti-fouling organic electrochemical transistor to C-reactive protein is 0.106 pg / mL.

[0184] Example 22

[0185] A preparation method of a sensor based on an intrinsically anti-fouling organic electrochemical transistor is as follows:

[0186] (1) The channel is modified with a conductive polymer material containing choline phosphate groups by electrochemical polymerization to prepare an intrinsically anti-fouling channel. Using as the monomer, the channel as the working electrode, a platinum mesh as the counter electrode, and Ag / Ag⁺ as the reference electrode, cyclic voltammetry is applied for polymerization with a scanning range of -0.6 to 1.06 V and a scanning speed of 100 mV / s to obtain a channel modified with choline phosphate group modified conductive polymer material;

[0187] (2) A method of spin coating is used to coat a layer of a phosphorylcholine group - modified conductive polymer material with a thickness of 10 nm on the gate to prepare an intrinsic anti - fouling gate;

[0188] (3) The intrinsic anti - fouling gate modified with the phosphorylcholine group - modified conductive polymer material and the intrinsic anti - fouling channel together form a sensor based on an intrinsic anti - fouling organic electrochemical transistor.

[0189] The sensitivity of the sensor based on the intrinsic anti - fouling organic electrochemical transistor to C - reactive protein is 13.1 μA / dec; the detection time of the sensor based on the intrinsic anti - fouling organic electrochemical transistor to C - reactive protein is 58 s; the detection limit (LOD) of the sensor based on the intrinsic anti - fouling organic electrochemical transistor to C - reactive protein is 0.104 pg / mL.

[0190] Example 23

[0191] A method for preparing a sensor based on an intrinsic anti - fouling organic electrochemical transistor, the specific steps are as follows:

[0192] (1) An electrochemical polymerization method is used to modify a conductive polymer material containing phosphorylcholine groups on the channel to prepare an intrinsic anti - fouling channel. Using as a monomer, using the channel as the working electrode, a platinum mesh as the counter electrode, and Ag / Ag⁺ as the reference electrode, applying cyclic voltammetry for polymerization, the scanning range is - 0.6~1.06 V, and the scanning speed is 100 mV / s, to obtain a channel modified with a phosphorylcholine group - modified conductive polymer material;

[0193] (2) An electrochemical polymerization method is used to modify the phosphorylcholine group - modified conductive polymer material on the gate to prepare an intrinsic anti - fouling gate. Using as a monomer, using the gate as the working electrode, a platinum mesh as the counter electrode, and Ag / Ag⁺ as the reference electrode, applying cyclic voltammetry for polymerization, the scanning range is - 0.6~1.17 V, and the scanning speed is 100 mV / s, to obtain a gate modified with a phosphorylcholine group - modified conductive polymer material;

[0194] (3) The intrinsic anti - fouling gate modified with the phosphorylcholine group - modified conductive polymer material and the intrinsic anti - fouling channel together form a sensor based on an intrinsic anti - fouling organic electrochemical transistor.

[0195] The sensitivity of the sensor based on the intrinsic anti - fouling organic electrochemical transistor to C - reactive protein is 13 μA / dec; the detection time of the sensor based on the intrinsic anti - fouling organic electrochemical transistor to C - reactive protein is 60 s; the detection limit (LOD) of the sensor based on the intrinsic anti - fouling organic electrochemical transistor to C - reactive protein is 0.107 pg / mL.

[0196] Example 24

[0197] A preparation method of a sensor based on an intrinsically anti-fouling organic electrochemical transistor is as follows:

[0198] (1) A layer of 10 nm thick phosphorylcholine group modified conductive polymer material is coated on the channel by spin coating to prepare an intrinsically anti-fouling channel;

[0199] (2) The phosphorylcholine group modified conductive polymer material is modified on the gate by electrochemical polymerization to prepare an intrinsically anti-fouling gate. Using as the monomer, the gate as the working electrode, a platinum mesh as the counter electrode, and Ag / Ag+ as the reference electrode, cyclic voltammetry is applied for polymerization with a scanning range of -0.6 to 1.17 V and a scanning speed of 100 mV / s to obtain a gate modified with phosphorylcholine group modified conductive polymer material;

[0200] (3) The intrinsically anti-fouling gate modified with phosphorylcholine group modified conductive polymer material and the intrinsically anti-fouling channel together form a sensor based on an intrinsically anti-fouling organic electrochemical transistor.

[0201] The sensitivity of the sensor based on the intrinsically anti-fouling organic electrochemical transistor to C-reactive protein is 13.2 μA / dec; the detection time of the sensor based on the intrinsically anti-fouling organic electrochemical transistor to C-reactive protein is 57 seconds; the detection limit (LOD) of the sensor based on the intrinsically anti-fouling organic electrochemical transistor to C-reactive protein is 0.109 pg / mL.

[0202] Example 25

[0203] A preparation method of a sensor based on an intrinsically anti-fouling organic electrochemical transistor is as follows:

[0204] (1) The phosphorylcholine group-containing conductive polymer material is modified on the channel by electrochemical polymerization to prepare an intrinsically anti-fouling channel. Using as the monomer, the channel as the working electrode, a platinum mesh as the counter electrode, and Ag / Ag+ as the reference electrode, cyclic voltammetry is applied for polymerization with a scanning range of -0.6 to 1.06 V and a scanning speed of 100 mV / s to obtain a channel modified with phosphorylcholine group modified conductive polymer material;

[0205] (2) A layer of 10 nm thick phosphorylcholine group modified conductive polymer material is coated on the gate by spin coating to prepare an intrinsically anti-fouling gate;

[0206] (3) The intrinsically anti-fouling gate modified with phosphorylcholine group modified conductive polymer material and the intrinsically anti-fouling channel together form a sensor based on an intrinsically anti-fouling organic electrochemical transistor.

[0207] The sensitivity of the sensor based on the intrinsically anti-fouling organic electrochemical transistor to C-reactive protein is 13.4 μA / dec; the detection time of the sensor based on the intrinsically anti-fouling organic electrochemical transistor to C-reactive protein is 58 seconds; the limit of detection (LOD) of the sensor based on the intrinsically anti-fouling organic electrochemical transistor to C-reactive protein is 0.11 pg / mL.

Claims

1. A sensor based on an intrinsic anti-fouling organic electrochemical transistor, comprising a source electrode, a drain electrode, a gate electrode, and a channel disposed between the source electrode and the drain electrode, characterized in that, The gate is composed of a modified conductive polymer material with phosphorylcholine groups modified on the surface of a gold electrode, forming an intrinsically anti-fouling gate. The channel is an intrinsically anti-fouling channel modified with a phosphorylcholine group-modified conductive polymer material, which can achieve rapid detection and real-time monitoring of biomarkers under a constant gate voltage in a complex biological environment.

2. The sensor based on an intrinsic anti-fouling organic electrochemical transistor according to claim 1, characterized in that The zwitterionic modified conductive polymer materials modified on the surfaces of the gate and the channel contain structural units shown in Formula (I) and Formula (II); Among them, Formula (I) is the phosphorylcholine group-modified conductive polymer material modified on the gate, and the number of polymer repeating units is m; Formula (II) is the phosphorylcholine group-modified conductive polymer material modified on the channel, and the number of polymer repeating units is n; In formulas (I) and (II), are repeating units of the polymer main chain; -L1- and -L2- are linking groups between the phosphorylcholine group and the polymer main chain; - R1 is Can be independently of each other as Any one of or its derivatives. The intrinsically anti-fouling organic electrochemical transistor sensor can rapidly detect and real-time monitor C-reactive protein under a constant gate voltage in a complex biological environment.

3. The sensor based on an intrinsic anti-fouling organic electrochemical transistor according to claim 2, wherein, The sensing sensitivity of the intrinsically anti-fouling organic electrochemical transistor sensor to C-reactive protein is greater than 7 μA / dec; The detection limit of the intrinsically anti-fouling organic electrochemical transistor sensor for C-reactive protein is not higher than 1 pg / mL; During the real-time detection under a constant gate voltage of the intrinsically anti-fouling organic electrochemical transistor sensor, the applied gate voltage is not greater than 0.7 V; The detection time of the intrinsically anti-fouling organic electrochemical transistor for C-reactive protein does not exceed 120 seconds; The non-specific response of the intrinsically anti-fouling organic electrochemical transistor sensor to bovine serum albumin is not greater than 1 μA.

4. The sensor based on an intrinsically anti-fouling organic electrochemical transistor according to claim 2, wherein Each may independently be any one of or its derivatives.

5. The sensor based on an intrinsic anti-fouling organic electrochemical transistor according to claim 4, characterized in that, the sensing sensitivity of the intrinsically anti-fouling organic electrochemical transistor sensor to C-reactive protein is greater than 10 μA / dec; the detection limit of the intrinsically anti-fouling organic electrochemical transistor sensor for C-reactive protein is not higher than 0.5 pg / mL; during the real-time detection under a constant gate voltage of the intrinsically anti-fouling organic electrochemical transistor sensor, the applied gate voltage is not greater than 0.5 V; the detection time of the intrinsically anti-fouling organic electrochemical transistor for C-reactive protein does not exceed 100 seconds; the non-specific response of the intrinsically anti-fouling organic electrochemical transistor sensor to bovine serum albumin is not greater than 0.5 μA.

6. The sensor based on an intrinsically anti-fouling organic electrochemical transistor according to claim 2, wherein independently selected from any one of or its derivatives 7. A sensor based on an intrinsic anti-fouling organic electrochemical transistor according to claim 6, wherein, the sensing sensitivity of the intrinsically anti-fouling organic electrochemical transistor sensor to C-reactive protein is greater than 13 μA / dec; the detection limit of the intrinsically anti-fouling organic electrochemical transistor sensor for C-reactive protein is not higher than 0.11 pg / mL; during the real-time detection under a constant gate voltage of the intrinsically anti-fouling organic electrochemical transistor sensor, the applied gate voltage is not greater than 0.4 V; the detection time of the intrinsically anti-fouling organic electrochemical transistor for C-reactive protein does not exceed 60 seconds; the non-specific response of the intrinsically anti-fouling organic electrochemical transistor sensor to bovine serum albumin is not greater than 0.3 μA.

8. A sensor based on an intrinsic anti-fouling organic electrochemical transistor according to claims 1 to 7, characterized in that, The preparation method of the intrinsic anti-fouling organic electrochemical transistor sensor is as follows: the phosphorylcholine group-modified conductive polymer material is directly modified on the gate and the channel by an electrochemical method or a spin-coating method.

9. The intrinsic anti-fouling organic electrochemical transistor sensor according to any one of claims 1 to 8, characterized in that, It can achieve precise in-situ rapid detection and real-time monitoring of C-reactive protein in clinical samples.

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