Flexible organic electrochemical transistor for non-invasive detection of hormones and method of making the same

Abstract

The application discloses a flexible organic electrochemical transistor for noninvasive detection of sex hormones and a preparation method thereof. The flexible organic electrochemical transistor comprises a source electrode, a drain electrode, a gate electrode and a channel arranged on a substrate, and the channel is located between the parallel arranged source electrode and drain electrode. The source electrode, the drain electrode, the gate electrode and the channel are all solidified from ink containing a conductive polymer composite material, and the conductive polymer composite material comprises a polymer of 3,4-ethylenedioxythiophene monomer, polystyrene sulfonic acid and lithium bis-trifluoromethylsulfonylimide. The surface of the gate electrode or the channel is deposited with gold nanoparticles, and the surface of the gold nanoparticles is provided with hormone recognition antibodies or aptamers. The application introduces gold nanoparticles on the surface of the conductive polymer gate electrode or the channel, and fixes the hormone recognition antibodies or aptamers, so that the sub-femtomolar sex hormone detection is realized by using the channel current change of the electrochemical transistor. The sex hormones with extremely low concentration can be noninvasively detected, and the rapid real-time monitoring of the sex hormone concentration is realized.

Description

Technical Field

[0001] This invention belongs to the field of detection technology, specifically relating to a flexible organic electrochemical transistor for non-invasive detection of sex hormones and its preparation method. Background Technology

[0002] Small molecule steroid hormones with biological activity are directly related to human growth, development, and health. Although steroid hormones are present in extremely low concentrations in the body, they play a crucial role in promoting the maturation of sexual organs, the development of secondary sexual characteristics, and maintaining sexual function. Currently, the conventional method for detecting sex hormones involves chemiluminescence immunoassay in a blood sample. This method generally requires specialized equipment and personnel, involves invasive blood sample collection, and is cumbersome, costly, and does not provide real-time results, thus hindering the widespread adoption and development of timely sex hormone detection.

[0003] Furthermore, the extremely low concentrations of sex hormones in vivo pose a major challenge to their detection. To address this issue, detection methods need to achieve low detection limits and high sensitivity. Electrochemical sensing, as an efficient, rapid, and simple method, has been widely used in the analysis and detection of biomolecules. Currently, relatively mature electrochemical sensors for sex hormones include carbon nanotube paper-based electrochemical sensors (see Yang Wang, Jinping Luo, Juntao Liu, Xinrong Li, Zhuang Kong, Hongyan Jin, Xinxia Cai. Electrochemical integrated paper-based immunosensor modified with multi-walled carbon nanotubes nanocomposites for point-of-care testing of 17β-estradiol. Biosensors and Bioelectronics. 2018, 107, 47-53) and magnetic particle electrochemical sensors (see Beatriz Arévalo, Verónica Serafín, José Francisco Beltrán-Sánchez, Juan Aznar-Poveda, José Antonio López-Pastor, Antonio Javier García-Sánchez, Joan García-Haro, Susana Campuzano, Paloma) - José M. Pingarrón. Simultaneous determination of four fertility-related hormones insaliva using disposable multiplexed immunoplatforms coupled to a custom-designed and field-portable potentiostat. Analytical Methods. 2021, 13(31), 3471-3478, etc. Although these electrochemical sensors can perform qualitative and quantitative detection of sex hormones, they still have drawbacks such as high detection limits, low sensitivity, high cost, and poor stability and reproducibility.

[0004] Organic electrochemical transistors (OETTs), as a novel electronic device structure, possess the signal amplification function of transistors and offer advantages such as simple operation, low operating voltage, biocompatibility, and low cost, leading to their widespread application in the detection of small biological molecules both in vivo and in vitro. However, research on OETTs in the detection of extremely low concentrations of sex hormones remains incomplete.

[0005] Therefore, developing a flexible, highly sensitive organic electrochemical transistor device capable of real-time detection of sex hormone levels is of great significance for non-invasive and timely clinical monitoring of sex hormones. Summary of the Invention

[0006] This invention aims to solve at least one of the technical problems existing in the prior art. To this end, this invention proposes a flexible organic electrochemical transistor for non-invasive detection of sex hormones and its preparation method. The organic electrochemical transistor introduces gold nanoparticles onto the surface of a conductive polymer gate or channel, and immobilizes hormone-recognizing antibodies or aptamers. It utilizes changes in the channel current of the electrochemical transistor to achieve sub-femtosecond-level sex hormone detection, enabling non-invasive detection of extremely low concentrations of sex hormones in saliva or sweat, and achieving rapid real-time monitoring of sex hormone concentrations.

[0007] To solve the above-mentioned technical problems, a first aspect of the present invention provides a flexible organic electrochemical transistor, including a source, a drain, a gate, and a channel disposed on a substrate, wherein the channel is located between the source and the drain disposed in parallel.

[0008] The source, drain, gate, and channel are all formed by curing ink containing conductive polymer composite material, which includes a polymer of 3,4-ethylenedioxythiophene monomer, polystyrene sulfonic acid, and lithium bis(trifluoromethanesulfonyl)imide (PEDOT:PSS / LiTFSI).

[0009] Gold nanoparticles are deposited on the surface of the gate or the channel, and the surface of the gold nanoparticles is provided with hormone recognition antibodies or aptamers.

[0010] Specifically, the flexible organic electrochemical transistor of this invention uses a conductive polymer composite material PEDOT:PSS / LiTFSI as the electrode, and introduces gold nanoparticles on the surface of the conductive polymer gate or channel to immobilize hormone recognition antibodies or aptamers. Utilizing the excellent binding ability of gold nanoparticles to biomolecules and their large specific surface area, the immobilization performance of antibodies or aptamers on the conductive polymer film is improved. The more antibodies or aptamers immobilized, the more antigen molecules will specifically bind, thereby causing changes in electrical signals on the conductive polymer surface and thus improving detection performance.

[0011] Meanwhile, the transistor of the present invention is an all-polymer flexible transistor, which achieves high flexibility sensing performance based on stretchable conductive polymer. By modifying different parts (gate or channel) of the organic electrochemical transistor and adjusting different doping states of the conductive polymer, various types of sensor devices can be prepared. By using signals such as statistical transconductance, maximum source-drain current and real-time current, sex hormones can be detected, and various devices with excellent detection effects can be obtained.

[0012] Preferably, the hormone recognition antibody includes a progesterone monoclonal antibody or an estradiol monoclonal antibody.

[0013] Preferably, the aptamer includes an estradiol-specific recognition nucleic acid aptamer.

[0014] Preferably, the surface of the gold nanoparticles is further bound with bovine serum albumin or 6-mercaptohexanol.

[0015] Preferably, the substrate is a flexible resin material; more preferably, the flexible resin material is polyethylene terephthalate (PET).

[0016] A second aspect of the present invention provides a method for fabricating a flexible organic electrochemical transistor, the method comprising the following steps:

[0017] (1) The source and drain electrodes are prepared by coating an ink containing conductive polymer composite material onto a substrate using a mask plate method.

[0018] (2) Coating the channel between the source and drain electrodes with an ink containing a conductive polymer composite material and drying it to form a film;

[0019] (3) The ink containing conductive polymer composite material is coated on the substrate and dried to form a film to obtain the gate;

[0020] (4) Gold nanoparticles are first deposited on the surface of the gate or the channel treated in step (2); then hormone recognition antibodies or aptamers are fixed to obtain the flexible organic electrochemical transistor.

[0021] Preferably, the preparation steps of the ink containing conductive polymer composite material are as follows: a polymer of 3,4-ethylenedioxythiophene monomer with a solid content of 1.1-1.3 wt% and an aqueous solution of polystyrene sulfonic acid are mixed with a lithium bis(trifluoromethanesulfonyl)imide solution at a volume ratio of (8-12):1.

[0022] Preferably, in steps (2) and (3), the drying and film formation is carried out at 120-140°C for 10-15 minutes.

[0023] Preferably, in step (4), the preparation steps of the fixed hormone recognition antibody or aptamer are as follows: an antibody solution or aptamer solution is added dropwise to the surface of the deposited gold nanoparticles and incubated at room temperature for 10-15 hours; then bovine serum albumin solution or 6-mercaptohexanol solution is added dropwise and incubated at room temperature for 1-2 hours; after washing the membrane layer with 6-mercaptohexanol solution, bovine serum albumin solution is added dropwise again and incubated at room temperature for another 1-2 hours to obtain the final product.

[0024] Preferably, the concentration of the antibody solution is 80-120 μg / mL.

[0025] Preferably, the concentration of the aptamer solution is 0.5-1.5 μM.

[0026] Preferably, the concentration of the bovine serum albumin solution is 0.5-1.5 mg / mL.

[0027] Preferably, the concentration of the 6-mercaptohexanol solution is 1-3 μM.

[0028] A third aspect of the present invention provides the application of the above-described flexible organic electrochemical transistor in sex hormone detection.

[0029] Preferably, the sex hormone includes progesterone or estradiol.

[0030] Preferably, the test sample includes saliva or sweat, enabling non-invasive testing.

[0031] A fourth aspect of the present invention provides a sensor comprising the above-described flexible organic electrochemical transistor.

[0032] Compared with the prior art, the above-described technical solution of the present invention has at least the following technical effects or advantages:

[0033] (1) The flexible organic electrochemical transistor of the present invention introduces gold nanoparticles onto the surface of a conductive polymer electrode. Utilizing the excellent binding ability of gold nanoparticles to biomolecules and their large specific surface area, the immobilization performance of antibody aptamers on the conductive polymer film is improved. The more antibodies immobilized, the more antigen molecules will specifically bind, thereby causing changes in the electrical signal on the conductive polymer surface. Results confirm that PEDOT:PSS / LiTFSI modified with gold nanoparticles, as the gate of the organic transistor, possesses excellent detection performance, exhibiting superior linearity and an extremely wide detection range.

[0034] (2) The flexible organic electrochemical transistor of the present invention utilizes the inherent signal amplification function of the transistor structure to amplify the minute signal generated by the binding of extremely low concentration antigen molecules with antibodies, thereby making it easier to capture the signal on the instrument and achieving the beneficial effects of improving sensitivity and lowering the detection limit. This device combines the advantages of good biocompatibility, low operating voltage, adjustable electrochemical window, simple and readily available materials, low cost, and simple and convenient preparation process of electrochemical transistors, realizing a flexible electronic device that can be applied to the detection of extremely low concentration sex hormones, which is expected to lower the detection threshold and become popular in people's daily lives.

[0035] (3) This invention applies the PEDOT:PSS / LiTFSI conductive polymer to organic electrochemical transistors. Utilizing the flexibility of PEDOT:PSS and the excellent detection sensitivity and configurational flexibility of organic electrochemical transistors, flexible organic electrochemical transistor devices with different configurations produce different detection effects. Therefore, when using the device, the modification sites and detection methods can be selected according to the actual situation to achieve better detection results. This invention achieves the detection of extremely low concentrations of sex hormones while being more flexible, convenient, and faster; it also provides a reference for advancements in the detection of small biological molecules in wearable flexible electronics and personalized medicine.

[0036] (4) This invention utilizes a modified aptamer-based flexible organic electrochemical transistor to detect two sex hormones, progesterone and estradiol. By optimizing the gate area and gate thickness, extremely low concentrations of sex hormones are detected based on the transistor-amplified signal. Simultaneously, this invention also achieves the detection of relatively low concentrations of salivary sex hormones, demonstrating broad application prospects for timely clinical diagnosis of sex hormones through non-invasive methods. Attached Figure Description

[0037] Figure 1 This is a flowchart illustrating the fabrication process of the modified gate flexible organic electrochemical transistor of Example 1;

[0038] Figure 2 This is a flowchart illustrating the fabrication process of the modified channel flexible organic electrochemical transistor of Example 1;

[0039] Figure 3 This is a schematic diagram of the structure of the flexible organic electrochemical transistor prepared in Example 1;

[0040] Figure 4 Transfer curves of the flexible organic electrochemical transistor prepared for Experimental Example 1 under different concentrations of antigen;

[0041] Figure 5 Transconductance curves of the flexible organic electrochemical transistor prepared for Experimental Example 1 under different concentrations of antigen;

[0042] Figure 6 Standard curves of the change in maximum transconductance versus the logarithm of concentration for the flexible organic electrochemical transistor prepared for Example 1 under different concentrations of antigen;

[0043] Figure 7 The transfer curves of the flexible organic electrochemical transistor prepared for Experimental Example 2 under different antigen concentrations and the relationship between the maximum source-drain current and the antigen concentration;

[0044] Figure 8 Real-time variation curves of source and drain currents of the flexible organic electrochemical transistor prepared for Experiment Example 3 under different concentrations of antigen.

[0045] Figure 9 The transfer curves of the flexible organic electrochemical transistor prepared in Example 4 under each modification step of the nucleic acid aptamer;

[0046] Figure 10 The transfer curves of flexible organic electrochemical transistors fabricated with gates of different areas in Experimental Example 5 and the relationship between source and drain currents and estradiol concentrations are shown in the figure.

[0047] Figure 11 For Example 6, transfer curves of estradiol were obtained using flexible organic electrochemical transistors with gates prepared at different dilution ratios.

[0048] Figure 12 Real-time variation curves of source and drain currents of the flexible organic electrochemical transistor prepared for Experimental Example 6 under different concentrations of estradiol.

[0049] Figure 13 The transfer curves of the flexible organic electrochemical transistor prepared for Experimental Example 7 under different concentrations of estradiol and the relationship between source and drain current and progesterone concentration are shown in the figure. Detailed Implementation

[0050] The present invention will now be described in detail with reference to embodiments to facilitate understanding of the invention by those skilled in the art. It is particularly important to note that the embodiments are merely illustrative of the invention and should not be construed as limiting the scope of protection of the invention. Non-essential improvements and adjustments made to the invention by those skilled in the art based on the above description should still fall within the scope of protection of the invention. Furthermore, all raw materials mentioned below, unless otherwise specified, are commercially available products; all process steps or preparation methods not mentioned in detail are process steps or preparation methods known to those skilled in the art.

[0051] Example 1

[0052] A flexible organic electrochemical transistor for sex hormone detection, such as Figure 1-2 As shown, it includes the following steps:

[0053] (1) The PET substrate was ultrasonically cleaned in a 50% (v / v) ethanol aqueous solution for 15 minutes and then dried with nitrogen gas.

[0054] (2) Mix an aqueous solution of PEDOT:PSS with a solid content of 1.1-1.3wt% (Clevios PH1000) with a LiTFSI solution at a volume ratio of 10:1. After stirring for 3 minutes, a homogeneous solution is obtained. The concentration of PEDOT:PSS in the solution is 1wt% and the concentration of LiTFSI is 2wt%, which is denoted as PEDOT:PSS / LiTFSI.

[0055] (3) Using a mask method, PEDOT:PSS / LiTFSI (10mg / mL) prepared in step (2) is drop-coated onto a PET substrate as the source and drain, with a channel area of ​​5mm×0.2mm between the source and drain.

[0056] (4) Drop 5 μL of the PEDOT:PSS / LiTFSI solution (concentration of 1-10 mg / mL) prepared in step (2) into the channel treated with oxygen plasma and dry at 130 °C;

[0057] (5) The PEDOT:PSS / LiTFSI solution (concentration of 1 mg / mL) obtained in step (2) after dilution with deionized water was drop-coated onto PET as a gate, and then dried naturally to form a film. After that, it was dried at 130°C for 10 min.

[0058] (6) 100 μL of 1 mM tetrachloroauric acid solution was dropped onto the gate obtained in step (5). Using an Ag / AgCl electrode as the reference electrode (standard potential of 0.2224 V at 25 °C) and a platinum electrode as the counter electrode, gold nanoparticles were deposited on the gate surface by cyclic voltammetry (-0.2 V to 0.6 V, 10 cycles).

[0059] (7) Add 40 μL of a 100 μg / mL progesterone monoclonal antibody solution to the gate after gold nanoparticle deposition in step (6) and incubate at room temperature for 12 hours; or, add 100 μL of a 1 μM nucleic acid aptamer solution specifically recognizing sex hormones to the gate after gold nanoparticle deposition in step (6) and incubate at room temperature for 12 hours; wherein:

[0060] The sequence of the progesterone aptamer is: 5`-GATTAACATTAGCCCACCGCCCACC-C6-HS-SH-3`. The sequence of the estradiol aptamer is: 5`-SH C6-AAGGGATGCCGTTTGGGCCCAAGTTCGGCATAGTG-3`;

[0061] (8) After incubating the antibody in step (7), add 40 μL of 1 mg / mL bovine serum albumin solution to the gate and incubate at room temperature for 2 hours; or, after incubating the aptamer in step (7), add 100 μL of 2 mM 6-mercaptohexanol solution to the electrode and incubate at room temperature for 1 hour; after cleaning the gate with the added 6-mercaptohexanol solution, add another 100 μL of 1 mg / mL bovine serum albumin solution and incubate at room temperature for 1 hour.

[0062] (9) Steps (5)-(8) above are the preparation process for modifying the gate; the preparation process for modifying the channel is the same as that for the gate, only the modification object "gate" in steps (5)-(8) needs to be replaced with "channel".

[0063] A schematic diagram of the flexible organic electrochemical transistor fabricated in this embodiment is shown below. Figure 3 As shown, the flexible organic electrochemical transistor includes a source 200, a drain 300, a gate 400, and a channel 500 disposed on a substrate 100, wherein the source 200 and the drain 300 are arranged in parallel and form the channel 500. Before conducting sex hormone tests, the flexible organic electrochemical transistor needs to be placed in an electrolyte solution to cover the surface of the transistor with a layer of electrolyte 600, and then connected to a transistor tester (Keithley 2612) to perform a blank test of the transistor transfer curve.

[0064] Unless otherwise specified, the electrolyte used in the following experiments is 1x phosphate buffer solution, the antibody is progesterone monoclonal antibody, and the antigen is progesterone. The aptamer is an estradiol-specific recognition nucleic acid aptamer, and the analyte is estradiol. Low doping refers to a LiTFSI doping concentration of 0.2-0.5 wt% in PEDOT:PSS, and high doping refers to a doping concentration of 1-5 wt%, with a PEDOT:PSS dilution concentration of 0.25-1 mg / mL.

[0065] Experimental Example 1

[0066] Gates, sources, and drains of different doped materials were placed in an electrolyte, and a series of antigen standard solutions of varying concentrations were quantitatively added to perform transfer curve testing. The test results are as follows: Figure 4 As shown, where: Figure 4 A indicates a device with a gate made of highly doped PEDOT:PSS, a channel made of highly doped diluted PEDOT:PSS, and antibody-modified channel. Figure 4 B indicates a device with a highly doped PEDOT:PSS gate, a highly doped diluted PEDOT:PSS channel, and an antibody-modified gate. Figure 4 C indicates a device with an Ag / AgCl gate, a highly doped diluted PEDOT:PSS channel, and antibody-modified channel.

[0067] The transconductance is the first derivative of the transfer curve, and the result is as follows: Figure 5 As shown, where: Figure 5 A indicates a device with a gate made of highly doped PEDOT:PSS, a channel made of highly doped diluted PEDOT:PSS, and antibody-modified channel. Figure 5 B indicates a device with a highly doped PEDOT:PSS gate, a highly doped diluted PEDOT:PSS channel, and an antibody-modified gate. Figure 5 C indicates a device with an Ag / AgCl gate, a highly doped diluted PEDOT:PSS channel, and antibody-modified channel.

[0068] The maximum transconductance change (ΔGm) at the current concentration can be obtained by calculating the difference between the maximum transconductance value and the initial maximum value.

[0069]

[0070] ΔGm max =Gm maxn -Gm max0

[0071] Among them: I DS Source-drain current value; V G Gate voltage; Gm maxn : Transconductance value at the current concentration; Gm max0 The initial transconductance value. Plotting concentration on the x-axis and the maximum transconductance change on the y-axis yields the standard curve for the current sensor, as shown below. Figure 6 As shown, where: Figure 6 A indicates a device with a gate made of highly doped PEDOT:PSS, a channel made of highly doped diluted PEDOT:PSS, and antibody-modified channel. Figure 6B indicates a device with a highly doped PEDOT:PSS gate, a highly doped diluted PEDOT:PSS channel, and an antibody-modified gate. Figure 6 C indicates a device with an Ag / AgCl gate, a highly doped diluted PEDOT:PSS channel, and antibody-modified channel.

[0072] The sensing principle of this device utilizes the specific recognition and binding of antibodies to antigens, forming non-conductive immune complexes on the surface of conductive polymers, thus hindering the ion pathway between the electrode and the electrolyte. When antibodies are modified on the channel, the resulting immune complexes cover the channel surface, obstructing the doping / dedoping process of ions in the channel, resulting in a decrease in the transistor's transconductance. When antibodies are modified on the gate, the resulting immune complexes reduce the effective voltage applied to the channel by the gate, leading to a decrease in both transconductance and gate current, and causing a shift in the transconductance curve peak. Figure 5 As can be seen, the maximum transconductance change value has a certain linear relationship with the antigen concentration. The higher the antigen concentration, the greater the transconductance decrease. This conclusion is consistent with the expected design.

[0073] This experiment fabricated three different configurations of sex hormone-sensing flexible electrochemical transistors by changing the antibody modification sites and gate materials: Type A: a device with a highly doped PEDOT:PSS gate, a highly doped diluted PEDOT:PSS channel, and antibody modification in the channel; Type B: a device with a highly doped PEDOT:PSS gate, a highly doped diluted PEDOT:PSS channel, and antibody modification in the gate; and Type C: a device with an Ag / AgCl gate, a highly doped diluted PEDOT:PSS channel, and antibody modification in the channel. Figure 4-6 The experimental results showed that the type A device exhibited the highest sensitivity, the type B device had the best linearity, and the type C device had the lowest detection limit. This indicates that the flexible electrochemical transistor for sex hormone sensing can better meet application requirements by flexibly selecting device materials or antibody modification sites.

[0074] Experimental Example 2

[0075] By comparing the antibody-modified interface of unmodified gold nanoparticles with that of antigen detection, the influence of gold nanoparticle modification on antigen assay was investigated. The results are as follows: Figure 7 As shown, where: Figure 7 A and Figure 7 B represents the transfer curves of the flexible organic electrochemical transistor with channel-deposited gold nanoparticles under different antigen concentrations and the relationship between the maximum source-drain current and the antigen concentration. Figure 7 C and Figure 7D represents the transfer curves of a flexible organic electrochemical transistor without gold nanoparticles deposited in the channel under different antigen concentrations, and the relationship between the maximum source / drain current and the antigen concentration. Figure 7 It can be seen that the channel after gold nanoparticle deposition exhibits better linearity in the antigen test with the same concentration gradient, proving that depositing gold nanoparticles on the modified interface is more conducive to antigen detection.

[0076] Experimental Example 3

[0077] A flexible organic electrochemical transistor (OLED) was fabricated using a lightly doped gate and a channel modified with diluted, lightly doped antibody. This transistor was then used for real-time sensing of sex hormones. The real-time source-drain current variation curves of this flexible OLED under different antigen concentrations are shown in the figure below. Figure 8 As shown. By Figure 8 It is observed that the source-drain current of the transistor suddenly decreases upon the addition of an antigen greater than 3 pM, and then tends to stabilize, forming a step-like current change. This current change process corresponds to the process of antigen-antibody binding and the formation of immune complexes in Experiment 1, which is in line with expectations. This also confirms that flexible organic electrochemical transistors can be used for rapid real-time monitoring of sex hormones, exhibiting an extremely low detection limit (approximately 30 pM) and a wide detection range (30 pM to 2 μM), and can be applied to achieve non-invasive detection and dynamic monitoring of sex hormones at pM levels in saliva and sweat.

[0078] Test Example 4

[0079] A flexible organic electrochemical transistor was fabricated using low-doped PEDOT:PSS, with a channel of low-doped diluted PEDOT:PSS and a gate modified with a progesterone aptamer. The sex hormone progesterone was detected using this flexible organic electrochemical transistor with a gate modified with a progesterone aptamer. The results are as follows: Figure 9 As shown. Wherein: Figure 9 A represents the transfer curve of the flexible organic electrochemical transistor at each modification step of the nucleic acid aptamer. Figure 9 B represents the transfer curves of a gate-modified progesterone-recognized nucleic acid aptamer flexible organic electrochemical transistor at different progesterone concentrations. Figure 9 C represents the relationship between the source-drain current of the flexible organic electrochemical transistor at a gate voltage of 0.4V and the progesterone concentration.

[0080] The transfer curves characterizing the stepwise modification process of the flexible organic electrochemical transistor are as follows: Figure 9 As shown in Figure A, incubation with gold nanoparticles, aptamers, 6-mercaptohexanol, and bovine serum albumin all resulted in a shift in the transfer curve, demonstrating the successful modification of these substances. The response of the flexible organic electrochemical transistor to different concentrations of progesterone is shown in Figure A. Figure 9As shown in Figure B, the transfer curve gradually shifts negatively with increasing progesterone concentration. This is because the aptamer on the gate of the flexible organic electrochemical transistor binds to progesterone, leading to a change in capacitance at the gate / electrolyte interface, which in turn reduces the source-drain current. Figure 9 By statistically analyzing the source-drain currents at a gate voltage of 0.4V, it can be determined that this flexible organic electrochemical transistor exhibits a good linear response to progesterone in the range of 500fM-500nM (R0). 2 =0.99), proving that this flexible organic electrochemical transistor can be used for the quantitative detection of progesterone.

[0081] Experimental Example 5

[0082] A flexible organic electrochemical transistor was fabricated using gold nanoparticles-modified low-doped PEDOT:PSS, with a channel of low-doped diluted PEDOT:PSS and an estradiol aptamer-modified gate. To achieve better estradiol detection, the gate area and thickness were optimized. The flexible organic electrochemical transistor with an estradiol aptamer-modified gate was then tested, and the results are as follows: Figure 10 As shown. Wherein: Figure 10 A shows the transfer curves of a flexible organic electrochemical transistor with a gate diameter of 0.9 cm under different concentrations of estradiol. Figure 10 B is a graph showing the relationship between the source and drain currents of a flexible organic electrochemical transistor with a gate diameter of 0.9 cm and the concentration of estradiol at a gate voltage of 0.1 V. Figure 10 C represents the transfer curves of a flexible organic electrochemical transistor with a gate diameter of 0.6 cm under different concentrations of estradiol; Figure 10 D is a graph showing the relationship between the source-drain current and estradiol concentration of a flexible organic electrochemical transistor with a gate diameter of 0.6 cm at a gate voltage of 0.1 V; Figure 10 E represents the transfer curves of a flexible organic electrochemical transistor with a gate diameter of 0.4 cm at different concentrations of estradiol. Figure 10 It can be seen that flexible organic electrochemical transistors with gate diameters of 0.9-0.4 cm exhibit different responses to estradiol and have different detection ranges. Among them, the current variation is greatest when the gate diameter is 0.9 cm for different concentrations of estradiol.

[0083] Experimental Example 6

[0084] A flexible organic electrochemical transistor was fabricated using low-doped PEDOT:PSS modified with gold nanoparticles, with the channel being low-doped diluted PEDOT:PSS, and PEDOT:PSS diluted by 10 times (10×) to 80 times (80×) as the gate, and estradiol aptamer modified on the gate. Figure 11Transfer curves of estradiol to flexible organic electrochemical transistors fabricated with gates of different dilution factors are shown, where: Figure 11 A represents the transfer curves of a flexible organic electrochemical transistor with a gate of 10× diluted PEDOT:PSS at different concentrations of estradiol. Figure 11 B represents the transfer curves of a flexible organic electrochemical transistor with a gate of 20× diluted PEDOT:PSS at different concentrations of estradiol. Figure 11 C represents the relationship between the source-drain current and estradiol concentration of the flexible organic electrochemical transistor with a gate voltage of 0.1V corresponding to a gate voltage of 20× diluted PEDOT:PSS; Figure 11 D represents the transfer curves of a flexible organic electrochemical transistor with a gate of 40× diluted PEDOT:PSS at different concentrations of estradiol. Figure 11 E represents the relationship between the source-drain current and estradiol concentration of a flexible organic electrochemical transistor with a gate voltage of 0.1V corresponding to a gate voltage of 40× diluted PEDOT:PSS. Figure 11 F represents the transfer curves of a flexible organic electrochemical transistor with a gate of 80× diluted PEDOT:PSS at different concentrations of estradiol. Figure 11 G represents the relationship between the source-drain current and estradiol concentration of a flexible organic electrochemical transistor with a gate voltage of 0.1V corresponding to a gate voltage of 80× diluted PEDOT:PSS.

[0085] Depend on Figure 11 It is known that, under the same gate area, the gate at a dilution factor of 40× exhibits the largest transfer curve shift. Therefore, a gate diameter of 0.9 cm and a PEDOT:PSS dilution factor of 40× are preferred as the optimal conditions for this transistor to detect estradiol. Statistical analysis of the source-drain current at a gate voltage of 0.1V shows that this flexible organic electrochemical transistor exhibits good linearity for estradiol concentrations ranging from 0.05 fM to 500 nM, demonstrating that the optimized flexible organic electrochemical transistor can detect estradiol over a wide linear range. Real-time sensing tests of estradiol were performed using the optimized flexible organic electrochemical transistor, and the results are as follows... Figure 12 As shown, the addition of estradiol in the concentration range of 500 fM-500 nM resulted in a decrease in the source-drain current, a trend consistent with the results of the transfer curve test. These results demonstrate that this transistor holds promise for playing a significant role in real-time sex hormone detection and other related fields, providing accurate and reliable analytical tools for key areas such as clinical diagnosis and disease monitoring.

[0086] Experimental Example 7

[0087] A flexible organic electrochemical transistor was fabricated using an Ag / AgCl gate electrode and a channel of low-doped diluted PEDOT:PSS modified with gold nanoparticles. An estradiol aptamer was then applied to the gate electrode. By modifying the channel with gold nanoparticles, the estradiol aptamer could bind to the gold nanoparticles via thiol groups and become immobilized on the channel surface. The aptamer, after binding to the target material, hindered ion doping / dedoping of the channel material, thus leading to a decrease in channel current. The transfer curves of the flexible organic electrochemical transistor with the estradiol aptamer-modified channel to different concentrations of estradiol are shown below. Figure 13 As shown. Wherein: Figure 13 A represents the transfer curves of the flexible organic electrochemical transistor at different concentrations of estradiol; Figure 13 B represents the relationship between the source-drain current of the flexible organic electrochemical transistor at a gate voltage of 0.1V and the estradiol concentration.

[0088] Depend on Figure 13 It can be seen that the channel current gradually decreases with increasing estradiol concentration, which is consistent with the theoretical trend. In the concentration range of 5fM-5nM, the channel current has a linear relationship with the estradiol concentration, proving that the flexible electrochemical transistor with channel-modified aptamer can be used as another transistor configuration for the quantitative detection of estradiol.

[0089] For those skilled in the art, several simple deductions or substitutions can be made without departing from the inventive concept, without requiring creative effort. Therefore, any simple improvements made to this invention by those skilled in the art based on the disclosure of this invention should be within the scope of protection of this invention. The above embodiments are preferred embodiments of this invention, and all processes similar to this invention and equivalent changes should fall within the scope of protection of this invention.

Claims

1. A flexible organic electrochemical transistor, characterized in that, It includes a source, a drain, a gate, and a channel disposed on a substrate, wherein the channel is located between the source and the drain disposed in parallel. The source, drain, gate, and channel are all formed by curing ink containing conductive polymer composite material, which includes a polymer of 3,4-ethylenedioxythiophene monomer, polystyrene sulfonic acid, and lithium bis(trifluoromethanesulfonyl)imide. The preparation steps of the ink containing the conductive polymer composite material are as follows: a polymer of 3,4-ethylenedioxythiophene monomer with a solid content of 1.1-1.3 wt% and an aqueous solution of polystyrene sulfonic acid are mixed with a lithium bis(trifluoromethanesulfonyl)imide solution at a volume ratio of (8-12):1; and a low-doped diluted PEDOT:PSS is used, wherein the low doping refers to the doping concentration of LiTFSI in PEDOT:PSS being 0.2-0.5 wt% and the dilution concentration of PEDOT:PSS being 0.25-1 mg / mL; The diameter of the gate is 0.6-0.9 cm; Gold nanoparticles are deposited on the surface of the gate or the channel, and hormone recognition antibodies or aptamers are provided on the surface of the gold nanoparticles. The hormone recognition antibody includes a progesterone monoclonal antibody or an estradiol monoclonal antibody, and the aptamer includes an estradiol-specific recognition nucleic acid aptamer.

2. The flexible organic electrochemical transistor according to claim 1, characterized in that, The surface of the gold nanoparticles is also bound with bovine serum albumin or 6-mercaptohexanol.

3. The flexible organic electrochemical transistor according to claim 1, characterized in that, The substrate is a flexible resin material.

4. A method for fabricating a flexible organic electrochemical transistor as described in any one of claims 1 to 3, characterized in that, Includes the following steps: (1) The source and drain electrodes are prepared by coating an ink containing conductive polymer composite material onto a substrate using a mask plate method. (2) Coating the channel between the source and drain electrodes with an ink containing a conductive polymer composite material and drying it to form a film; (3) The ink containing conductive polymer composite material is coated on the substrate and dried to form a film to obtain the gate; (4) Gold nanoparticles are first deposited on the surface of the gate or the channel treated in step (2); then hormone recognition antibodies or aptamers are fixed to obtain the flexible organic electrochemical transistor.

5. The method for fabricating a flexible organic electrochemical transistor according to claim 4, characterized in that, The preparation steps of the fixed hormone recognition antibody or aptamer are as follows: antibody solution or aptamer solution is dropped onto the surface of the membrane after gold nanoparticle deposition and incubated at room temperature for 10-15 hours; then bovine serum albumin solution or 6-mercaptohexanol solution is dropped onto the membrane and incubated at room temperature for 1-2 hours; after washing the membrane with 6-mercaptohexanol solution, bovine serum albumin solution is dropped onto the membrane and incubated at room temperature for another 1-2 hours to obtain the final product.

6. The application of the flexible organic electrochemical transistor as described in any one of claims 1 to 3 in sex hormone detection.

7. The application according to claim 6, characterized in that, The sex hormones include progesterone or estradiol; and / or, the test sample includes saliva or sweat.

8. A sensor, characterized in that, The sensor includes the flexible organic electrochemical transistor according to any one of claims 1 to 3.

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