Microneedle sensor based on electrochemical transistor and preparation method thereof

Abstract

The invention provides a microneedle sensor based on an electrochemical transistor and a preparation method of the microneedle sensor, and belongs to the technical field of biosensors. According to the sensor, the microneedle is used for collecting the skin interstitial fluid and is also used as a grid electrode of the OECT, so that the signal amplification characteristic of the OECT and the minimally invasive sampling advantage of the microneedle are combined, the minimally invasive, in-situ and real-time detection of the biomarker in the skin interstitial fluid is realized, the complexity and lag of in-vitro sampling in a traditional detection method are avoided, and the detection accuracy of the biomarker in the skin interstitial fluid is improved. The detection capability on low-concentration markers is improved, and a new technical scheme is provided for real-time monitoring of biomarkers.

Description

Technical Field

[0001] This invention belongs to the field of biosensor technology, specifically relating to a microneedle sensor based on electrochemical transistor (OECT) and its preparation method. Background Technology

[0002] With the development of personalized medicine and wearable health monitoring, the demand for real-time, continuous, and non-invasive detection of biomarkers is increasing. Interstitial fluid (ISF), as a body fluid highly correlated with blood components, is an important medium for monitoring various metabolic indicators and disease-related biomarkers. However, traditional detection methods usually rely on blood sampling, which involves complex procedures, high invasiveness, and inconvenience for continuous monitoring, making it difficult to meet the needs of long-term health management and immediate diagnosis.

[0003] Electrochemical sensors are widely used in biomarker detection due to their high sensitivity, simple structure, and ease of miniaturization. Among them, organic electrochemical transistors (OECTs) have become important candidates for next-generation biosensors due to their low operating voltage, strong signal amplification capability, and compatibility with flexible substrates. However, most existing OECT-based sensors employ planar electrode structures and rely on external bodily fluid samples for detection, still requiring in vitro sampling or the introduction of the analyte liquid through complex microfluidic systems, which limits their application in in-situ real-time monitoring.

[0004] Microneedle technology has seen rapid development in the fields of minimally invasive sampling and drug delivery in recent years. Hollow or solid microneedles can penetrate the skin surface in a minimally invasive manner to enter the interstitial fluid region rich in biological information, while avoiding the pain and infection risks associated with traditional acupuncture. Microneedle-based sensors have been used to detect glucose, amino acids, drug molecules, etc., but most are still at the level of electrode or colorimetric detection, lacking effective signal amplification mechanisms. Although combining organic electrochemical transistors with microneedle mechanisms can achieve in-situ signal amplification, the integrated design of the two is quite challenging due to the limited space of the microneedle structure and the complexity of ion transport paths.

[0005] Therefore, how to combine OECT with hollow microneedle structures to utilize the high sensitivity and signal amplification characteristics of OECT while leveraging the advantages of microneedles in in-situ sampling and biocompatibility, and construct an electrochemical transistor sensor that can be directly and continuously monitored in vivo, is a technical problem that urgently needs to be solved in this field. Summary of the Invention

[0006] To address the problems existing in the background technology, the present invention aims to provide a microneedle sensor based on electrochemical transistor (OECT) and its preparation method. This sensor not only uses microneedles to collect interstitial fluid from the skin, but also serves as the gate of OECT, thus combining the signal amplification characteristics of OECT with the minimally invasive sampling advantages of microneedles. This enables minimally invasive, in-situ, and real-time detection of biomarkers in interstitial fluid, avoiding the cumbersome and delayed in vitro sampling of traditional detection methods, and improving the detection capability for low-concentration biomarkers, providing a new technical solution for real-time monitoring of biomarkers.

[0007] To achieve the above objectives, the technical solution of the present invention is as follows:

[0008] A microneedle sensor based on an electrochemical transistor includes: a substrate, a transistor, an array of hollow microneedles, and an ion gel;

[0009] The transistor is located on the substrate surface and includes a source, a drain, and a PEDOT:PSS trench between the source and drain.

[0010] The channel consists of a drain and a source, which have the same structure and are symmetrically arranged about the center line of the channel. The drain is composed of an "L"-shaped metal strip and a rectangular block, with the rectangular block connected to one end of the "L"-shaped metal strip. The two rectangular blocks of the drain and source are adjacent to each other but do not touch. The rectangular area between the two rectangular blocks serves as the channel area, and the surface of the channel area is covered with a PEDOT:PSS film to form a PEDOT:PSS channel.

[0011] The array-type hollow microneedle structure includes a U-shaped substrate and several microneedles arranged in an array on the horizontal surface of the U-shaped substrate. The two vertical sides of the U-shaped substrate are in contact with the substrate surface to form a cavity region, and the transistor is located in the cavity region. The microneedles are conical, hollow inside, and connected to the upper cavity. The outer surfaces of the microneedles and the substrate are metallized to serve as the gate of the transistor.

[0012] The ion gel is disposed in the chamber region and serves as the electrolyte for the transistor, enabling ion conduction between the gate and the PEDOT:PSS channel.

[0013] Furthermore, the aspect ratio of the transistor channel is 20:1.

[0014] Furthermore, the microneedle has a height of 0.8~1mm, a bottom diameter of 0.5~0.6mm, and a through hole with a diameter of 0.15~0.2mm in the needle wall; the height of the chamber (the height of the vertical side of the base) is 2mm.

[0015] Furthermore, the substrate is a single-sided silicon oxide wafer, and the oxide layer can provide an insulating layer to reduce leakage current or electric field interference, etc. The oxide layer thickness is 800~1000nm; the array-type hollow microneedle structure is formed by 3D printing photocurable resin, and the photocurable resin material is polyurethane acrylic resin.

[0016] Furthermore, the ionogel comprises polyvinyl alcohol (PVA) ionogel, glycerol, and inorganic salt to enhance its ionic conductivity and anti-drying properties; wherein the glycerol content is 5-15 wt%, and the inorganic salt is potassium chloride with a concentration of 0.05-0.15 mol / L.

[0017] A method for fabricating a microneedle sensor based on an electrochemical transistor includes the following steps:

[0018] S1. Prepare a single-sided silicon oxide wafer substrate;

[0019] S2. Patterned source and drain electrodes are fabricated on the oxide surface of the substrate using a photolithography-magnetron sputtering process;

[0020] S3. Preparation of PEDOT:PSS channel: Spin-coat the entire substrate surface with PEDOT:PSS solution and anneal it; then prepare a photoresist pattern in the channel region between the source and drain, remove the PEDOT:PSS in the non-channel region by photolithography and plasma etching, and retain only the PEDOT:PSS film in the channel region; finally remove the photoresist to obtain the desired PEDOT:PSS channel;

[0021] S4. The OECT substrate is encapsulated, and a silver wire is used to connect the other end of the unconnected rectangular block of the "L"-shaped metal strip to realize the output of electrical signals;

[0022] S5. An array of hollow microneedle structures was prepared by 3D printing and photocuring resin molding, and its outer surface was metallized to form a conductive layer, which served as the gate of a transistor.

[0023] S6. Inject ion gel into the hollow microneedles and their internal cavities to fill the microneedle holes and the cavity above them, and solidify it through a freeze-thaw crosslinking method to form a stable ion gel.

[0024] Furthermore, in S2, both the source and drain electrodes use gold as the electrode material; at the same time, in order to enhance the adhesion between the gold film and the substrate, a layer of titanium metal can be deposited on the substrate surface first using radio frequency magnetron sputtering as an adhesion layer, and then gold can be deposited on it using DC magnetron sputtering.

[0025] Furthermore, the surface of the microneedle is specifically modified with bio-recognition technology to achieve selectivity for target molecules.

[0026] Furthermore, the specific process of freeze-thaw crosslinking of the ionogel in S6 is as follows: first freeze for several hours, then refrigerate for a period of time, and finally thaw at room temperature to the gel state.

[0027] This invention also provides an application of the above-mentioned microneedle sensor based on electrochemical transistors, the specific process of which is as follows:

[0028] Microneedle arrays are directly contacted with the body fluids of the target organism or penetrate the skin to enter the interstitial fluid, allowing specific recognition elements on the microneedle gate surface to interact with target molecules in situ. A highly efficient ion transport channel is achieved by filling the microneedles and their cavities with PVA ion gel, enabling the action of target molecules to be rapidly coupled to the PEDOT:PSS channel, modulating its conductivity. Under appropriate gate-source voltage conditions, changes in drain current are measured, and the measured current signal is analyzed to obtain the concentration of the target analyte, achieving in-situ, rapid, and highly sensitive biomarker detection.

[0029] The mechanism of this invention is as follows:

[0030] This invention leverages the ion-electron coupling mechanism of organic electrochemical transistors (OECTs) and the minimally invasive sampling characteristics of microneedles to achieve rapid in-situ detection of biomarkers. The sensor uses a PEDOT:PSS thin film as the channel material, whose conductivity can be reversibly controlled by ion injection and migration within the channel. Hollow microneedles, after metallization, serve as the transistor gate and can undergo specific biorecognition modifications on their surface, thus endowing them with selectivity for target molecules. The microneedles directly penetrate the skin into the interstitial fluid, eliminating the need for additional body fluid extraction; target molecules interact with the gate in situ. PVA ionogel filling the microneedles and their cavities constructs a highly efficient ion transport channel, enabling rapid coupling of ion signals to the channel, triggering changes in the PEDOT:PSS conductivity, and converting this into a significant electrical signal output, thereby achieving in-situ, rapid, and highly sensitive detection.

[0031] In summary, due to the adoption of the above technical solution, the beneficial effects of the present invention are:

[0032] 1. Enables in-situ detection: Utilizes hollow microneedles to directly collect subcutaneous interstitial fluid, achieving in-situ detection under minimally invasive conditions, avoiding the cumbersome steps of body fluid extraction and in vitro analysis in traditional methods;

[0033] 2. Fast response characteristics: PVA ion gel constructs a stable and efficient ion transport channel, enabling changes in target molecules to modulate the conductivity of the OECT channel within seconds, achieving rapid detection; when no ion gel is introduced, the device has no obvious electrical signal output;

[0034] 3. High sensitivity: The high transconductance of OECT converts minute fluctuations in ion concentration into significant electrical signals, ensuring the sensitivity and reliability of the detection results;

[0035] 4. Compact and easy-to-integrate sensor structure: The source, drain and channel are patterned using photolithography, and the microneedles also serve as gates, resulting in miniaturized overall devices suitable for wearable applications;

[0036] 5. Wide applicability: This sensor enables rapid in-situ detection of various biomarkers, including but not limited to glucose and uric acid; the detection range for glucose is 5 μM to 3 mM, and the detection range for uric acid is 0.1 μM to 1 mM. These results demonstrate that the sensor has good versatility and can meet the application needs of various scenarios such as health monitoring, disease screening, and personalized medicine. Attached Figure Description

[0037] Figure 1 This is a schematic diagram of the overall structure of the microneedle sensor based on OECT of the present invention.

[0038] Figure 2 This is a structural diagram of the transistor in the OECT-based microneedle sensor of this invention;

[0039] (a) is a schematic diagram, and (b) is a physical image.

[0040] Figure 3 This is an optical micrograph of the microneedles of the present invention.

[0041] Figure 4 Optical micrograph of microneedles after metallization;

[0042] In the figure, (a) is the top view and (b) is the side view.

[0043] Figure 5 Comparison images of OECT-based microneedle sensors before and after filling with PVA ionogel.

[0044] Figure 6 This is a diagram of the microneedle portion of an OECT-based microneedle sensor.

[0045] Figure 7 This is the transfer characteristic curve of the sensor of the present invention.

[0046] Figure 8 This is the output characteristic curve of the sensor of the present invention.

[0047] Figure 9 The image shows the I-T response curves of the sensor of this invention to different concentrations of glucose.

[0048] Figure 10The image shows the I-T response curves of the sensor of this invention to different concentrations of uric acid. Detailed Implementation

[0049] To make the objectives, technical solutions, and advantages of the present invention clearer, the present invention will be further described in detail below with reference to the embodiments and accompanying drawings.

[0050] A microneedle sensor based on OECT, the schematic diagram of which is shown below. Figure 1 As shown, it includes: a substrate, a transistor, an array of hollow microneedle structures, and an ion gel;

[0051] The schematic diagram of the transistor structure is as follows: Figure 2 As shown, (a) is a schematic diagram and (b) is a physical image, the crystal...

[0052] The body tube is located on the substrate surface and includes a source, a drain, and a PEDOT:PSS channel between the source and drain. The drain and source have the same structure and are symmetrically arranged about the center line of the channel. The drain consists of an "L"-shaped metal strip and two rectangular blocks. The first rectangular block is connected to one end of the "L"-shaped metal strip, and the second rectangular block is connected to the other end of the "L"-shaped metal strip. The second rectangular block is only used as an electrode lead to increase the contact area of ​​the electrode lead and can be omitted. The two first rectangular blocks of the drain and source are adjacent to each other but do not contact each other. The rectangular area between the two first rectangular blocks is the channel area. The surface of the channel area is covered with a PEDOT:PSS film to form the PEDOT:PSS channel.

[0053] The array-type hollow microneedle structure includes a U-shaped substrate and several microneedles arranged in an array on the horizontal surface of the U-shaped substrate. The two vertical sides of the U-shaped substrate are in contact with the substrate to form a cavity region. The microneedles are conical, hollow inside, and connected to the upper cavity. The outer surfaces of the microneedles and the substrate are metallized to serve as transistor gates.

[0054] The ion gel is disposed in the chamber region and serves as the electrolyte for the transistor, enabling ion conduction between the gate and the PEDOT:PSS channel.

[0055] Figure 3 The images shown are optical micrographs of the microneedles of the present invention, wherein (a) and (b) are top views of the microneedles, and the two views are taken at different magnifications.

[0056] (c) is a side view at high magnification. The microneedles are prepared by 3D printing with photocurable resin and are arranged in a regular array. Each microneedle has an oblique hole in the middle for the introduction of interstitial fluid and OECT signal transmission. The height of the microneedles is about 1 mm.

[0057] Figure 4These are optical micrographs of microneedles after metallization, where (a) is a top view, showing the microneedle array and each

[0058] (a) shows the hole distribution of the microneedles; (b) is a side view that clearly shows the microneedles and channels. After metallization, the surface of the microneedles becomes conductive, thus enabling them to serve as gates for OECT.

[0059] Figure 5 Comparison images of OECT-based microneedle sensors before and after filling with PVA ionogel, showing the microneedle channels before filling.

[0060] It has a hollow structure, which is filled and occupied by PVA ionogel, thus forming a stable ion-conducting pathway.

[0061] Figure 6 The diagram shows the transistor and microneedle components of an OECT-based microneedle sensor. The top part shows the OECT transistor structure, and the bottom part shows a schematic diagram of the metallized microneedle. Both the microneedle and the transistor are 1cm × 1cm in size.

[0062] Example 1

[0063] A method for fabricating a microneedle sensor based on OECT includes the following steps:

[0064] Step 1. Transistor fabrication:

[0065] Step 1.1. Prepare a single-sided silicon oxide substrate, wherein the substrate is a single-sided silicon oxide wafer with an oxide layer thickness of 1000 nm;

[0066] Step 1.2. Spin-coat AZ5214 photoresist onto the oxide layer surface of the silicon wafer. The spin-coating conditions are: first 1000 r / min for 10 s, then 3000 r / min for 30 s. After spin-coating, place the silicon wafer on a 100 ℃ hot stage for 60 s for pre-baking. Then perform the first exposure for 4 s. After the exposure, place the silicon wafer on a 120 ℃ hot stage for 90 s and perform the second exposure for 40 s. Finally, place the silicon wafer in the developer for 40 s to remove the photoresist from the non-patterned areas, obtaining the patterned mask.

[0067] Step 1.3. Sputter an Au layer on the mask using magnetron sputtering; to enhance the adhesion between the gold film and the substrate, first sputter a titanium metal layer on the substrate surface as an adhesion layer, wherein the titanium is sputtered using radio frequency magnetron sputtering with a sputtering power of 200W and a pre-sputtering time of 5 minutes, and deposited for 5 minutes under the same parameters; then gold is deposited on it using DC magnetron sputtering with a sputtering power of 50W and a sputtering time of 5 minutes, to obtain the source and drain electrode structure;

[0068] Step 1.4. Immerse the silicon wafer in acetone to remove the photoresist, and you will get the patterned gold source and drain electrodes;

[0069] Step 1.5. Spin-coat the entire silicon wafer surface with PEDOT:PSS solution. The spin-coating conditions are: 500 r / min for 6 s, then 2500 r / min for 30 s, followed by annealing at 120℃ for 60 minutes. Then, perform photolithography on the channel region between the source and drain electrodes using AZ6112 photoresist. The photoresist spin-coating conditions are: 1000 r / min for 10 s, then 3000 r / min for 30 s. After spin-coating, bake on a 100℃ hot plate for 60 s, expose for 4 s, and then develop in the developer for 45 s to obtain a rectangular photoresist pattern covering the channel region, which serves as a mask. Finally, use oxygen plasma etching to remove the PEDOT:PSS not covered by the photoresist. The thin film was etched with a power of 200W and an etching time of 240s. Finally, the device was immersed in acetone to remove the photoresist in the channel area, thus obtaining a regular rectangular PEDOT:PSS channel.

[0070] The PEDOT:PSS solution is composed of 94 wt% PEDOT:PSS (PH-1000), 5 wt% ethylene glycol, 1 wt% 3-glycidyl etheroxypropyltrimethoxysilane, and 0.1 wt% dodecylbenzenesulfonic acid;

[0071] Step 1.6. Encapsulate the entire device using SU-8 photoresist: Spin-coat the photoresist onto the substrate surface, first at 1000 r / min for 10 s, then at 5000 r / min for 30 s. Pre-bake by heating at 65 ℃ for 2 min and then at 95 ℃ for 5 min sequentially. Next, expose to ultraviolet light for 30 s. After exposure, post-bake by heating at 65 ℃ for 2 min and then at 95 ℃ for 5 min sequentially. Finally, develop the sample in a developer solution for 3 min 30 s to remove the photoresist from non-patterned areas, thus obtaining the desired patterned structure, exposing only the channel, source, and drain. Silver wires are used to bring out the electrode leads.

[0072] Step 2. Fabrication of an array of hollow microneedle structures;

[0073] Step 2.1. Hollow microneedles are prepared by 3D printing. The microneedles are formed by photocuring resin, and the photocuring resin material is polyurethane acrylic resin.

[0074] Step 2.2. Metallize the outer surface of the microneedle to form a conductive layer so that it can be used as the gate electrode of the transistor;

[0075] The conductive layer of the microneedle is made of gold and formed by magnetron sputtering. To improve the adhesion between the gold layer and the microneedle substrate, a titanium layer is first deposited on its surface as an adhesion layer. The titanium is deposited using radio frequency magnetron sputtering with a sputtering power of 200 W and a pre-sputtering time of 5 min, and then deposited for 5 min under the same parameters. Subsequently, a gold layer is deposited on the surface of the titanium layer using DC magnetron sputtering with a sputtering power of 50 W and a sputtering time of 6 min, thereby obtaining the metal conductive layer of the microneedle.

[0076] Step 3. Fill with iontophoresis gel:

[0077] PVA gel is injected into hollow microneedles and their internal cavities to fill the oblique holes and the cavity above the microneedles. The gel is then cured by a freeze-thaw crosslinking process to form a stable PVA ionogel.

[0078] The PVA ion gel is doped with glycerol and inorganic salt to enhance its ionic conductivity and resistance to drying; wherein the glycerol content is 10% and the inorganic salt is potassium chloride.

[0079] The specific parameters for the PVA ionogel freeze-thaw crosslinking curing method are: freeze for 12 hours, refrigerate for 4 hours, and then thaw at room temperature; thus, the required OECT-based microneedle sensor can be obtained.

[0080] Example 2

[0081] A method for preparing a microneedle glucose sensor based on OECT includes the following steps:

[0082] Step 1. Depositing platinum nanoparticles on microneedles

[0083] Step 1.1. Prepare the deposition solution. Dissolve 5 mM chloroplatinic acid in 0.05 M HCl and stir until completely dissolved. The resulting solution is used as the electrochemical deposition solution for platinum nanoparticles.

[0084] Step 1.2. Deposit platinum nanoparticles: Immerse the microneedles in the deposition solution and deposit them at a potential of -0.3V (relative to the Ag / AgCl reference electrode) for 60 seconds to obtain platinum nanoparticles on the surface of the microneedles, thereby improving the conductivity and catalytic activity of the microneedle surface.

[0085] Step 2. Glucose oxidase modification

[0086] Step 2.1. Prepare the enzyme solution by dissolving glucose oxidase (GOx) in chitosan (CS) solution and adding multi-walled carbon nanotubes (MWCNTs) to prepare a CS / GOx / MWCNT mixed solution. Stir the solution evenly to obtain a stable enzyme mixture. The concentration of GOx is 15 mg / mL, the concentration of CS is 1%, and the mass ratio of MWCNTs to CS is 1:3.

[0087] Step 2.2 Immerse the microneedles in the CS / GOx / MWCNT mixed solution to cover the surface of the microneedles with the enzyme solution, and refrigerate at 4°C overnight to allow glucose oxidase to be stably immobilized on the surface of the microneedles to form a biorecognition membrane;

[0088] Step 3. Membrane protection treatment

[0089] Nafion solution was dropped onto the surface of the microneedles to uniformly cover the entire surface, and then allowed to dry naturally. This allowed the Nafion membrane to adhere firmly to the surface of the biorecognition membrane, thereby enhancing the stability and selectivity of the membrane, preventing detachment and interference, and improving the long-term stability of the sensor in biological samples.

[0090] The Nafion solution is a perfluorosulfonic acid-based polymer with a concentration of 1%; thus, the desired OECT-based microneedle glucose sensor can be obtained.

[0091] Example 3

[0092] A method for fabricating a microneedle uric acid sensor based on OECT includes the following steps:

[0093] The microneedle gate modification steps in Example 3 are the same as those in Example 2, except that the glucose oxidase in step 2 is replaced with uricase and the enzyme concentration is adjusted to 10 mg / mL. The rest of the steps remain unchanged.

[0094] Figure 7 This is the transfer characteristic curve of the microneedle sensor based on OECT of the present invention, where the source-drain voltage V ds -0.2V, gate voltage V gs The scan is performed within the range of -0.4 to 0.6V. As can be seen from the graph, the drain current I... ds Significant modulation occurs with changes in gate voltage; the slope of the curve corresponds to the transconductance g. m Used to characterize the current amplification capability and response sensitivity to external signals of a device. A higher transconductance value means that a small change in gate voltage can cause a significant change in drain current, thereby improving sensing performance. The sensor of this invention operates at V... gs The transconductance reaches its maximum value of 9 mS at -0.2V, indicating that the device has excellent signal amplification capability and sensitivity, making it suitable for real-time detection of biomarkers. gsThe transistor is most sensitive to the input signal at -0.2V.

[0095] Figure 8 This is the output characteristic curve of the microneedle sensor based on OECT of the present invention, where the source-drain voltage V ds The gate voltage V varies within the range of 0–0.8 V. gs The voltage is adjustable within the range of 0–1 V, with a step interval of 0.1 V. As can be seen from the figure, the output curves under different gate voltage conditions show obvious differentiation, with V... dS As the voltage increases, the drain current gradually increases, indicating that the channel conductivity is effectively controlled by the gate voltage. The sensor of this invention can achieve continuous and controllable adjustment of the drain current under low-voltage drive, demonstrating the current amplification characteristics and good output response of OECT, and providing a stable electrical basis for the application of microneedle sensors in in-situ detection of biomarkers.

[0096] Figure 9 The image shows the I-T response curves of the sensor of this invention after modification with glucose enzyme biorecognition to different glucose concentrations, ranging from 1 μmol / L to 3 mmol / L. The OECT-based microneedle glucose sensor begins to generate a detectable current change at a glucose concentration of 5 μmol / L. When the concentration increases to approximately 3 mmol / L, the current response tends to saturate, indicating that the device has good detection range and response stability. Its experimental limit of detection is 5 μmol / L.

[0097] Figure 10 This image shows the I-T response curves of the sensor of this invention after modification with uricase biorecognition for different concentrations of uric acid, ranging from 0.1 μmol / L to 1 mmol / L. The microneedle uric acid sensor based on the OECT structure begins to show a detectable current change when the uric acid concentration reaches approximately 1 μmol / L. As the concentration further increases, the response current gradually increases and tends to saturate at approximately 1 mmol / L, indicating that the device has a wide detection range and good response stability. Its experimental limit of detection is 0.1 μmol / L.

[0098] The above description is merely a specific embodiment of the present invention. Any feature disclosed in this specification may be replaced by other equivalent or similar features unless otherwise specified. All disclosed features, or steps in all methods or processes, may be combined in any way except for mutually exclusive features and / or steps.

Claims

1. A microneedle sensor based on an electrochemical transistor, characterized in that, Including substrates, transistors, arrayed hollow microneedle structures, and ion gels; The transistor is located on the substrate surface and includes a source, a drain, and a PEDOT:PSS trench between the source and drain. The channel consists of a drain and a source with the same structure, arranged symmetrically about the center line of the channel. The drain is composed of an "L"-shaped metal strip and a rectangular block, with the rectangular block connected to one end of the "L"-shaped metal strip. The two rectangular blocks of the drain and source are adjacent to each other but do not touch. The rectangular area between the two rectangular blocks serves as the channel area, and the surface of the channel area is covered with a PEDOT:PSS thin film to form a PEDOT:PSS channel. The array-type hollow microneedle structure includes a U-shaped substrate and several microneedles arranged in an array on the horizontal surface of the U-shaped substrate. The two vertical sides of the U-shaped substrate are in contact with the substrate surface to form a cavity region, and the transistor is located in the cavity region. The microneedles are conical, hollow inside, and connected to the upper cavity. The outer surfaces of the microneedles and the substrate are metallized to serve as the gate of the transistor. The ion gel is disposed in the chamber region and serves as the electrolyte for the transistor, enabling ion conduction between the gate and the PEDOT:PSS channel.

2. The microneedle sensor based on electrochemical transistors as described in claim 1, characterized in that, The transistor channel aspect ratio is 20:

1.

3. The microneedle sensor based on electrochemical transistors as described in claim 1, characterized in that, The microneedle has a height of 0.8~1mm, a bottom diameter of 0.5~0.6mm, and a through hole with a diameter of 0.15~0.2mm in the needle wall. The height of the chamber is 2mm.

4. The microneedle sensor based on electrochemical transistors as described in claim 1, characterized in that, The substrate is a single-sided silicon oxide wafer with an oxide layer thickness of 800~1000nm; the array-type hollow microneedle structure is formed by 3D printing photocurable resin, and the photocurable resin material is polyurethane acrylic resin.

5. The microneedle sensor based on electrochemical transistors as described in claim 1, characterized in that, The ion gel comprises polyvinyl alcohol ion gel, glycerol, and inorganic salt; wherein the glycerol content is 5-15 wt%, and the inorganic salt is potassium chloride with a concentration of 0.05-0.15 mol / L.

6. A method for fabricating a microneedle sensor based on an electrochemical transistor as described in any one of claims 1-5, characterized in that, Includes the following steps: S1. Prepare a single-sided silicon oxide wafer substrate; S2. Patterned source and drain electrodes are fabricated on the oxide surface of the substrate using a photolithography-magnetron sputtering process; S3. Preparation of PEDOT:PSS channel: Spin-coat the entire substrate surface with PEDOT:PSS solution and anneal it; then prepare a photoresist pattern in the channel region between the source and drain, remove the PEDOT:PSS in the non-channel region by photolithography and plasma etching, and retain only the PEDOT:PSS film in the channel region; finally remove the photoresist to obtain the desired PEDOT:PSS channel; S4. The electrochemical transistor substrate is packaged by connecting a silver wire to the other end of the unconnected rectangular block of the "L"-shaped metal strip. To achieve the output of electrical signals; S5. An array of hollow microneedle structures was prepared by 3D printing and photocuring resin molding, and its outer surface was metallized to form a conductive layer, which served as the gate of a transistor. S6. Inject ion gel into the hollow microneedles and their internal cavities to fill the microneedle holes and the cavity above them, and solidify it through a freeze-thaw crosslinking method to form a stable ion gel.

7. The preparation method according to claim 6, characterized in that, In S2, both the source and drain electrodes use gold as the electrode material. To enhance the adhesion between the gold film and the substrate, a layer of titanium metal is first deposited on the substrate surface using radio frequency magnetron sputtering as an adhesion layer, and then gold is deposited on it using DC magnetron sputtering.

8. The preparation method according to claim 6, characterized in that, The surface of the microneedle is specifically modified with bio-recognition technology to achieve selectivity for target molecules.

9. The preparation method according to claim 6, characterized in that, The specific process of freezing-thawing crosslinking of the ionogel in S6 is as follows: first freeze for several hours, then refrigerate for a period of time, and finally thaw at room temperature to the gel state.

10. An application of a microneedle sensor based on an electrochemical transistor as described in any one of claims 1-5, characterized in that, The specific application process is as follows: The microneedle array is brought into direct contact with the body fluid of the target organism or penetrates the skin to enter the interstitial fluid, so that the specific recognition elements on the microneedle gate surface interact with the target molecules in situ. The PVA ionogel filled in the microneedle and its cavity serves as an ion transport channel, enabling the action of target molecules to be rapidly coupled to the PEDOT:PSS channel and modulating its conductivity changes. Under the condition of applying an appropriate gate-source voltage, the change of drain current is measured, and the measured current signal is analyzed to obtain the concentration of the target substance, thereby realizing the detection of biomarkers.

Images