Organic electrochemical transistor for improving biological monitoring performance, preparation method and application

Abstract

The invention belongs to the technical field of biosensing of organic electrochemical transistors, and particularly relates to an organic electrochemical transistor for improving biological monitoring performance, a preparation method and application. The organic electrochemical transistor comprises a substrate, a source electrode, a drain electrode, an active layer, an ionic gel layer and a bioactive solution layer, the source electrode and the drain electrode are deposited on the substrate, the active layer is attached above the source electrode and the drain electrode, the ionic gel layer is attached above the active layer, and the bioactive solution layer is attached above the ionic gel layer. The bioactive solution layer is composed of guar gum, glycerin and a metal chloride aqueous solution. The organic electrochemical transistor can be tightly attached to the biological epidermis, toxic and side effects on organisms are avoided, meanwhile, the OECT detection performance is improved, and the monitoring sensitivity is improved.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of organic electrochemical transistor biosensing, and particularly relates to an organic electrochemical transistor for improving biosensing performance, a preparation method and application. By preparing a buffer solution with biocompatible ions, the adhesion of the device to the biological surface can be effectively improved, and the detection performance can be improved. BACKGROUND

[0002] An organic electrochemical transistor (OECTs) is a three-terminal device composed of a source / drain electrode, an active layer, an electrolyte layer, and a gate electrode. It relies on the characteristics of ion and electron cooperative transmission and has the ability to monitor biological ion information in real time, and can be used in electrolyte ion detection, biological cell detection and other scenes. Due to low working voltage (<1 V) and good compatibility with water environment, it is widely used in the field of bioelectronics.

[0003] The electrolyte layer of OECTs is usually an aqueous solution, and the ions in it can penetrate into the active layer to produce electrochemical doping in the conductive channel, so that the device has high transconductance characteristics. To achieve biological monitoring, the ions generated by the organism (such as glucose, dopamine, NaCl, KCl, etc.) need to exchange ions with the active layer, so the device must be closely attached to the detection object. However, the active layer is mostly organic, and direct contact with biological tissue will have adverse effects. Although ion gel as an electrolyte layer can isolate the active layer and reduce oxidation, it still cannot solve the adhesion problem of the device to the biological surface, so how to improve the adhesion has become a research focus.

[0004] CN117347453A describes a multilayer porous semiconductor organic electrochemical transistor and its fabrication method. The organic electrochemical transistor includes a substrate layer, an electrode layer, a semiconductor layer, an ion gel layer, an electrolyte layer, and a gate electrode. It utilizes the increased interfacial contact between the electrolyte and the ion gel layer in the electrolyte layer to achieve high permeability, thus fabricating an organic electrochemical transistor with high transconductance, large drain current, and low hysteresis. This overcomes the shortcomings of electrochemical transistors where insufficient contact and low permeability between the electrolyte and semiconductor layers lead to unsatisfactory output current. CN119355090A describes a biosensor based on an organic electrochemical transistor and its fabrication method. Based on the capillary force of the conical micropores and the difference in hydrophilicity and hydrophobicity between the upper and lower surfaces of the device, sweat is spontaneously absorbed from the substrate side and transferred to the biofunctionalized vertical gold nanowire side, achieving automated sweat extraction and detection. CN118946219A discloses a fast-response fiber-optic vertical organic electrochemical transistor and its fabrication method. The method involves winding a thin-film source electrode around the curved surface of a fiber drain electrode to form a coaxial stepped source-drain electrode. Then, an organic semiconductor layer is loaded at the step to form a small-sized vertical channel, thereby obtaining a fast-response fiber-optic vertical organic electrochemical transistor that enables real-time monitoring of rapidly changing electrocardiogram signals within biological soft tissues. Summary of the Invention

[0005] To address the shortcomings of existing technologies, this invention provides an organic electrochemical transistor (OECT) for improving biomonitoring performance, its preparation method, and its application. This invention solves problems such as poor adhesion between the OECT and the target organism, and the toxicity risks associated with direct contact between the active layer's organic matter and the target organism. It allows for bioactivity monitoring by adhering to the organism's epidermis, avoiding toxic side effects and significantly improving OECT detection performance.

[0006] The technical solution of the present invention is an organic electrochemical transistor for improving biomonitoring performance, comprising a substrate, a source electrode, a drain electrode, an active layer, an ion gel layer, and a bioactive solution layer. The source electrode and the drain electrode are deposited on the substrate, the active layer is attached above the source electrode and the drain electrode, the ion gel layer is attached above the active layer, and the bioactive solution layer is attached above the ion gel layer.

[0007] The active layer is composed of PBDTT-2T and / or PBDTT-TT, preferably PBDTT-TT. The ionogel layer is composed of PVDF-HFP and dopants, with the mass ratio of PVDF-HFP to dopants being 1:1.5-3, preferably 1:2. The dopants include, but are not limited to, any one or any combination of LiTFSI, EMIMTFSI, and BMIMTFSI, preferably LiTFSI.

[0008] The bioactive solution layer is composed of guar gum, glycerol, and an aqueous solution of a metal chloride. The ratio of guar gum, glycerol, and the aqueous solution of the metal chloride is 140-170 mg: 18-25 ml: 0.5-0.8 ml, preferably 150 mg: 20 ml: 0.6-0.65 ml. The concentration of the chloride aqueous solution is 0.05-0.5 mol / L, preferably 0.1 mol / L. The metal chloride is any one or any combination of NaCl, KCl, FeCl3, FeCl2, AlCl3, and MgCl2, preferably NaCl and / or FeCl3.

[0009] The source and drain are each selected from Au, Ag, and PEDOT:PSS, with Au being the preferred choice.

[0010] The substrate is polyethylene terephthalate (PET).

[0011] A method for fabricating an organic electrochemical transistor to improve biomonitoring performance, comprising the following steps: (1) Vacuum evaporation to deposit the source and drain electrodes on the substrate; (2) Spin-coating the solution containing the polymer onto the source and drain electrodes, and drying to obtain the active layer; (3) Dissolve PVDF-HFP and dopant in an organic solvent, heat and mix, solidify to obtain an ion gel layer, and adhere the ion gel layer to the active layer; (4) Add guar gum and glycerol to the aqueous solution of metal chloride, heat and mix well to obtain a bioactive solution, and drop the bioactive solution onto the ion gel layer to form a bioactive solution layer.

[0012] Step (1): The substrate is ultrasonically cleaned with deionized water, acetone, and isopropanol for 15 minutes each, then dried with nitrogen and baked at 50°C. The substrate is polyethylene terephthalate (PET).

[0013] Step (1), when using vacuum evaporation, the vacuum degree is <3×10 -4 Pa, deposition rate is 0.5-0.7 Å / s.

[0014] In step (1), the source and drain are any one of Au, Ag, and PEDOT:PSS, preferably Au.

[0015] In step (2), the polymer is PBDTT-2T and / or PBDTT-TT, preferably PBDTT-TT; the concentration of the polymer is 3-5 mg / ml, preferably 4 mg / ml; the volume of the solution containing the polymer is 18-25 μl, preferably 20 μl; the solvent used includes, but is not limited to, any one or any combination of chloroform, acetone, dimethyl sulfoxide, and ethyl acetate, preferably chloroform.

[0016] Step (3): The mass ratio of PVDF-HFP to dopant is 1:1.5-3, preferably 1:2; the concentration of PVDF-HFP is 90-150 mg / mL, preferably 100 mg / mL; the organic solvent is any one or any combination of acetone, tetrahydrofuran, toluene, chloroform, and dimethylformamide, preferably acetone; the dopant is not limited to any one or any combination of LiTFSI, EMIMTFSI, and BMIMTFSI, preferably LiTFSI.

[0017] Step (3): Heat at 50 ℃ to mix evenly, and cure under constant temperature and humidity.

[0018] In step (4), the ratio of guar gum, glycerol and metal chloride aqueous solution is 140-170mg:18-25ml:0.5-0.8ml, preferably 150mg:20ml:0.6-0.65ml, and the concentration of chloride aqueous solution is 0.05-0.5mol / L, preferably 0.1mol / L; the metal chloride is any one or any combination of NaCl, KCl, FeCl3, FeCl2, AlCl3 and MgCl2, preferably NaCl and / or FeCl3.

[0019] The organic electrochemical transistor provided above by the present invention is used for monitoring the bioactivity of organisms attached to the epidermis, or for H2O2 detection.

[0020] This invention provides a method for monitoring bioactivity, which involves attaching a bioactive solution layer of an organic electrochemical transistor with improved biomonitoring performance provided above to a biological epidermis for bioactivity monitoring.

[0021] This invention provides a method for detecting H2O2, which involves contacting the test solution with the bioactive solution layer of an organic electrochemical transistor for improving biomonitoring performance provided above, to perform qualitative and / or quantitative detection of H2O2 in the test solution.

[0022] Compared with the prior art, the beneficial effects of the present invention are: 1. The gel covers the active layer to protect it and reduces toxicity upon contact. This is mainly because the organic toxicity cannot come into contact with the biological surface after a biocompatible solution is dropped onto the gel.

[0023] 2. Highly adaptable, it can be combined with other forms of organic electrochemical transistors. Using a viscous, biocompatible solution, it perfectly adheres to biological surfaces, allowing for the detection of biological data even if the organic electrochemical transistor itself lacks flexibility.

[0024] 3. Some ions, such as FeCl3 and FeCl2, can improve the performance of organic electrochemical transistors. Attached Figure Description

[0025] Figure 1 This is a schematic diagram of the organic electrochemical transistor of the present invention; wherein 1-substrate layer, 2-source and drain electrodes, 3-active layer, 4-ion gel layer, 5-bioactive solution layer, and 6-analyte.

[0026] Figure 2 The transfer characteristic curves and transconductance curves of an organic electrochemical transistor prepared using a biocompatible solution prepared with 0.1 mol / L NaCl solution.

[0027] Figure 3 Characteristic curves of organic electrochemical transistors prepared using biocompatible solutions with different metal salt solutions are shown. a) Biocompatible solution prepared using 0.1 mol / L NaCl solution, b) Biocompatible solution prepared using 0.1 mol / L FeCl3 solution, b) shows faster recovery of the initial state.

[0028] Figure 4 The 300-second cycle test curve of an organic electrochemical transistor prepared using a biocompatible solution prepared with 0.1 mol / L NaCl solution.

[0029] Figure 5 The reaction diagram of the Venus flytrap prepared in Example 1 is shown.

[0030] Figure 6 The source and drain current curves of the organic electrochemical transistor sensor prepared in Example 2 when detecting H2O2 concentration. Detailed Implementation

[0031] To make the technical means, creative features, objectives and effects of this invention easier to understand, the following embodiments are described in detail with reference to the accompanying drawings. It should be noted that the description of these embodiments is for the purpose of helping to understand this invention, but does not constitute a limitation of this invention.

[0032] Example 1 (1) Substrate: The polyethylene terephthalate (PET) substrate was placed in deionized water, acetone solution and isopropanol solution in sequence and ultrasonically cleaned for 15 minutes each. After cleaning, the PET was dried with a nitrogen gun and then placed in a clean petri dish and heated to 50°C to dry. (2) Vacuum deposition electrode: A 60 nm thick gold layer was deposited on the cleaned PET as the source and drain electrodes using vacuum deposition method, with a deposition rate of 0.5-0.7 Å / s.

[0033] (3) Preparation of active layer: The organic polymer PBDTT-TT was placed in a glass bottle containing chloroform and stirred to prepare a solution with a concentration of 4 mg / ml. The solution was then dissolved evenly and 20 μl was spin-coated onto the PET of the deposition source and drain electrode at 2000 r / min. The active layer was then obtained by heating in a vacuum oven at 80°C for 2 h.

[0034] (4) Preparation of biocompatible solution: Prepare 20 mL of 0.1 mol / L NaCl solution. Place the prepared solution in an ultrasonic cleaner and vibrate for 15 minutes to fully dissolve it. Take out a weighing bottle and put the fully dissolved sodium chloride solution and magnetic rotor into the weighing bottle. Heat the heating plate and put 150 mg of guar gum and 0.625 mL of glycerol into the weighing bottle. Place the weighing bottle on the heating plate and heat and stir until the solution is uniform and gel-like.

[0035] (5) Preparation of ion gel: Weigh 300mg PVDF-HFP into a small bottle, add 3 mL acetone, heat and stir on a 50 ℃ heating plate for about 2 hours until transparent gel is formed, then add 600mg LiTFSI and heat and stir for about 2 hours. After stabilization, cure at constant temperature and humidity for 1 week. After curing, cover the organic active layer.

[0036] (6) Connect the source and drain of the organic electrochemical transistor to a semiconductor parameter analysis instrument. Use a dropper to take 3 ml of the prepared biocompatible solution from the weighing bottle, then drop it onto the prepared organic electrochemical transistor ionogel, and place it on the back of the Venus flytrap leaf. At regular intervals, use a toothpick to touch the internal hairs of the Venus flytrap to trigger its fly-trapping mechanism. Figure 5 .

[0037] Example 2 (1) Substrate: The polyethylene terephthalate (PET) substrate was placed in deionized water, acetone solution and isopropanol solution in sequence and ultrasonically cleaned for 15 minutes each. After cleaning, the PET was dried with a nitrogen gun and then placed in a clean petri dish and heated to 50°C to dry. (2) Vacuum deposition electrode: A 60 nm thick gold layer was deposited on the cleaned PET as the source and drain electrodes using vacuum deposition method, with a deposition rate of 0.5-0.7 Å / s.

[0038] (3) Preparation of active layer: PBDTT-TT is placed in a glass bottle containing chloroform and stirred to prepare a solution with a concentration of 4 mg / ml. The solution is then dissolved evenly and 20 μl is spin-coated onto the PET of the deposition source and drain electrode at 2000 r / min. The active layer is then obtained by heating in a vacuum oven at 80°C for 2 h.

[0039] (4) Preparation of biocompatible solution: Prepare 20 mL of 0.1 mol / L NaCl solution. Place the prepared solution in an ultrasonic cleaner and vibrate for 15 minutes to fully dissolve it. Take out a weighing bottle and put the fully dissolved sodium chloride solution and magnetic rotor into the weighing bottle. Heat the heating plate and put 150 mg of guar gum and 0.625 mL of glycerol into the weighing bottle. Place the weighing bottle on the heating plate and heat and stir until the solution is uniform and gel-like.

[0040] (5) Preparation of ion gel: Weigh 300mg PVDF-HFP into a small bottle, add 3 mL acetone, heat and stir on a 50 ℃ heating plate for about 2 hours until transparent gel is formed, then add 600mg LiTFSI and heat and stir for about 2 hours. After stabilization, cure at constant temperature and humidity for 1 week. After curing, cover the organic active layer.

[0041] (6) Connect the source and drain of the organic electrochemical transistor to a semiconductor parameter analysis instrument. Using a dropper, take 3 ml of the prepared biocompatible solution from the weighing bottle and drop it onto the prepared organic electrochemical transistor ion gel. Add H2O2 of different concentrations to the biocompatible solution at intervals to obtain… Figure 6 The detected H2O2 concentration range was 10 nM-75 μM.

[0042] Example 3 (1) Substrate: The polyethylene terephthalate (PET) substrate was placed in deionized water, acetone solution and isopropanol solution in sequence and ultrasonically cleaned for 15 minutes each. After cleaning, the PET was dried with a nitrogen gun and then placed in a clean petri dish and heated to 50°C to dry. (2) Vacuum deposition electrode: A 60 nm thick gold layer was deposited on the cleaned PET as the source and drain electrodes using vacuum deposition method, with a deposition rate of 0.5-0.7 Å / s.

[0043] (3) Preparation of active layer: The organic polymer PBDTT-TT was placed in a glass bottle containing chloroform and stirred to prepare a solution with a concentration of 4 mg / ml. The solution was then dissolved evenly and 20 μl was spin-coated onto the PET of the deposition source and drain electrode at 2000 r / min. The active layer was then obtained by heating in a vacuum oven at 80°C for 2 h.

[0044] (4) Preparation of biocompatible solution: Prepare 20 mL of 0.1 mol / L NaCl solution (or other ionic solutions such as FeCl3). Place the prepared solution in an ultrasonic cleaner and vibrate for 15 minutes to fully dissolve it. Take out a weighing bottle and put 10 mL of fully dissolved sodium chloride solution and a magnetic rotor into the weighing bottle. Heat the heating plate, put 150 mg of guar gum and 0.625 mL of glycerol into the weighing bottle, place the weighing bottle on the heating plate and heat and stir until the solution is uniform and gel-like.

[0045] (5) Preparation of ion gel: Weigh 300mg PVDF-HFP into a small bottle, add 3 mL acetone, heat and stir on a 50 ℃ heating plate for about 2 hours until transparent gel is formed, then add 600mg LiTFSI and heat and stir for about 2 hours. After stabilization, cure at constant temperature and humidity for 1 week. After curing, cover the organic active layer.

[0046] (6) Connect the source and drain of the organic electrochemical transistor to the semiconductor parameter analyzer. Use a dropper to take 3 ml of the prepared biocompatible solution from the weighing bottle and then drop it onto the prepared organic electrochemical transistor ion gel. Soak it in a 0.1 mol / L NaCl solution (non-biocompatible solution). The gate is the gate of the semiconductor analyzer.

[0047] contrast Figure 3 The characteristic curves of organic electrochemical transistors prepared by biocompatible solutions containing NaCl (a) and FeCl3 (b) show that the organic electrochemical transistor prepared by the biocompatible solution containing FeCl3 (b) has a greater amplification factor for small currents, a lower threshold voltage, and is easier to detect small-amplitude action potentials. At the same time, the detected source-drain current will be greater under the action of OECTs.

[0048] The above embodiments are preferred embodiments of the present invention and are not intended to limit the scope of protection of the present invention. Various modifications or variations that can be made by those skilled in the art without creative effort within the scope of the appended claims are still within the scope of protection of this patent.

Claims

1. An organic electrochemical transistor for improving biomonitoring performance, characterized in that, The device includes a substrate, a source electrode, a drain electrode, an active layer, an ion gel layer, and a bioactive solution layer. The source electrode and the drain electrode are deposited on the substrate. The active layer is attached above the source electrode and the drain electrode. The ion gel layer is attached above the active layer. The bioactive solution layer is attached above the ion gel layer. The bioactive solution layer is composed of guar gum, glycerol, and an aqueous solution of metal chloride.

2. The organic electrochemical transistor according to claim 1, characterized in that, The active layer is composed of PBDTT-2T and / or PBDTT-TT; the ion gel layer is composed of PVDF-HFP and dopant, with a mass ratio of PVDF-HFP to dopant of 1:1.5-3.

3. The organic electrochemical transistor according to claim 1, characterized in that, The ratio of guar gum, glycerol, and metal chloride aqueous solution is 140-170 mg: 18-25 ml: 0.5-0.8 ml, the concentration of chloride aqueous solution is 0.05-0.5 mol / L, and the metal chloride is any one or any combination of NaCl, KCl, FeCl3, FeCl2, AlCl3, and MgCl2.

4. A method for preparing an organic electrochemical transistor to improve biomonitoring performance, characterized in that the step... include: (1) Vacuum evaporation to deposit the source and drain electrodes on the substrate; (2) Spin-coating the solution containing the polymer onto the source and drain electrodes, and drying to obtain the active layer; (3) Dissolve PVDF-HFP and dopant in an organic solvent, heat and mix, solidify to obtain an ion gel layer, and adhere the ion gel layer to the active layer; (4) Add guar gum and glycerol to the aqueous solution of metal chloride, heat and mix well to obtain a bioactive solution, and drop the bioactive solution onto the ion gel layer to form a bioactive solution layer.

5. The preparation method according to claim 4, characterized in that, In step (2), the polymer is PBDTT-2T and / or PBDTT-TT, the polymer concentration is 3-5 mg / ml, and the volume of the solution containing the polymer is 18-25 μl.

6. The preparation method according to claim 4, characterized in that, Step (3): The mass ratio of PVDF-HFP to dopant is 1:1.5-3, the concentration of PVDF-HFP is 90-150 mg / mL, the organic solvent is any one or any combination of acetone, tetrahydrofuran, toluene, chloroform, and dimethylformamide, and the dopant is not limited to any one or any combination of LiTFSI, EMIMTFSI, and BMIMTFSI.

7. The preparation method according to claim 4, characterized in that, In step (4), the ratio of guar gum, glycerol and metal chloride aqueous solution is 140-170mg:18-25ml:0.5-0.8ml, the concentration of chloride aqueous solution is 0.05-0.5mol / L, and the metal chloride is any one or any combination of NaCl, KCl, FeCl3, FeCl2, AlCl3 and MgCl2.

8. The organic electrochemical transistor according to any one of claims 1-3 or the organic electrochemical transistor prepared by any one of claims 4-7 is used for bioactivity monitoring of biological epidermis or for H2O2 detection.

9. A method for monitoring biological activity, characterized in that, The bioactive solution layer of the organic electrochemical transistor according to any one of claims 1-3 or the organic electrochemical transistor prepared by any one of claims 4-7 is adhered to the biological epidermis for bioactivity monitoring.

10. A method for detecting H2O2, characterized in that, The test solution is brought into contact with the bioactive solution layer of the organic electrochemical transistor according to any one of claims 1-3 or the organic electrochemical transistor prepared by any one of claims 4-7, to perform qualitative and / or quantitative detection of H2O2 in the test solution.

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