A vertical structure OECT flexible glucose sensor and a preparation method thereof

Abstract

This invention relates to the field of glucose electrochemical sensor technology, specifically to a vertically structured OECT flexible glucose sensor and its fabrication method. The sensor employs a vertical structure design, arranging the drain, source, and channel vertically, which improves the sensor's integration and reduces its size. Simultaneously, PVA doping enhances the electrochemical and mechanical properties of the PEDOT:PSS material, improving the electrochemical performance of the channel layer. Due to the vertical structure, the PEDOT:PSS-PVA composite material can be used to form a nanoscale flexible channel layer via high-speed spin coating, effectively shortening the electron path between the drain and source, significantly accelerating the device's response speed, greatly improving the channel current modulation efficiency, effectively increasing the transconductance of the channel layer, and also enhancing its flexibility. This allows the sensor to maintain good transconductance retention even under high periodic stress, enabling its application in wearable devices and other scenarios.

Description

Technical Field

[0001] This invention relates to the field of glucose electrochemical sensor technology, specifically to a vertical OECT flexible glucose sensor and its preparation method. Background Technology

[0002] Organic electrochemical transistors (OECTs), as a class of semiconductor devices that combine electronic and ionic conductivity, have shown broad application prospects in biosensing, especially in the field of small molecule detection, due to their excellent electrochemical activity, good biocompatibility, and inherent flexible integration potential.

[0003] Glucose, as a key indicator of human metabolism, plays a crucial role in the non-invasive detection of glucose in sweat for early screening, daily management, and real-time monitoring of exercise and health status in diabetes. Therefore, developing highly sensitive and stable glucose sensors using OECT (Optical Electron Conduction) technology has become a research hotspot in the field of bioelectronics. In existing technologies, OECT glucose sensors generally employ a horizontal structure design. These sensors typically define micron-scale channels on a planar substrate using micro / nano fabrication techniques, utilizing conductive polymers (such as poly(3,4-ethylenedioxythiophene):polystyrene sulfonate, PEDOT:PSS) as the active channel material, and combining them with biological enzymes (such as glucose oxidase, GOx) to recognize specific biomolecules.

[0004] Traditional horizontal OECT glucose sensors (such as the flexible sensor disclosed in CN 120131007 B) arrange the drain, source, and gate in the same plane, resulting in a large overall sensor size. When applied to wearable devices, they often encounter bending or even folding problems. Furthermore, the conventional channel material PEDOT:PSS has weak mechanical flexibility and is prone to cracking in bending or humid environments, resulting in a short lifespan.

[0005] Furthermore, since the channel length of traditional horizontal OECT is typically on the order of micrometers, this greatly limits the depth and uniformity of ion injection from the electrolyte into the channel, resulting in low modulation efficiency of the channel current and ultimately low transconductance, often below 10 mS. This inherent low transconductance directly restricts the device's ability to amplify weak biological signals, making the detection sensitivity of glucose sensors insufficient. Their detection limit often remains above 1 micromolar (μM), making it difficult to meet the demand for accurate detection of trace glucose in sweat (typically at the nanomolar (nM) to micromolar (μM) level). Summary of the Invention

[0006] To address the technical problems of short lifespan and low detection accuracy of traditional horizontal OECT glucose sensors, this application provides a vertical OECT flexible glucose sensor and its fabrication method.

[0007] The sensor includes:

[0008] Substrate;

[0009] A bottom electrode is disposed on the upper surface of the substrate, and an adhesive layer is disposed on the side of the bottom electrode that contacts the substrate, and a conductive layer is disposed on the upper surface of the adhesive layer;

[0010] A channel layer is disposed on the upper surface of the conductive layer of the bottom electrode and is in electrical contact with the conductive layer. The channel layer is composed of PEDOT:PSS-PVA composite material.

[0011] A top electrode is disposed on the upper surface of the channel layer and is in electrical contact with the channel layer;

[0012] An insulating layer is disposed on the upper surface of the substrate;

[0013] A gate modification layer is disposed on the upper surface of the substrate, and an insulating layer is disposed around the gate modification layer;

[0014] The gate modification layer consists of a gate, a Prussian blue mediator layer, an enzyme complex layer, and a protective layer, arranged sequentially from bottom to top.

[0015] The preparation method provided by this invention includes the following steps:

[0016] The substrate is cleaned and dried.

[0017] A bottom electrode is formed by depositing a chromium thin film and a gold thin film sequentially from bottom to top on the upper surface of the substrate using thermal evaporation technology.

[0018] A PEDOT:PSS-PVA mixture was prepared and spin-coated and cured onto the upper surface of the bottom electrode to form a channel layer.

[0019] The top electrode region is defined using a shadow mask, and a gold thin film is deposited on the upper surface of the channel layer using a thermal evaporation process to form the top electrode;

[0020] Photoresist is spin-coated onto the upper surface of the top electrode, and photolithography is used to remove the photoresist on the channels and contacts, leaving a portion of the photoresist as an insulating layer.

[0021] A gate, a Prussian blue mediator layer, an enzyme complex layer, and a protective layer are sequentially formed from bottom to top on the upper surface of the substrate, ultimately forming a gate modification layer.

[0022] The technical effects and advantages of this invention are as follows: The flexible glucose sensor with a vertical OECT structure provided by this invention improves the sensor's integration and reduces its size by vertically arranging the drain, source, channel, and gate. Simultaneously, the vertical structure allows the PEDOT:PSS-PVA composite material to form a nanoscale flexible channel layer through a high-speed spin-coating process, effectively shortening the electron path between the drain and source, significantly accelerating the device's response speed, and greatly improving the modulation efficiency of the channel current, thus effectively increasing the transconductance of the channel layer. Furthermore, the PEDOT:PSS-PVA composite material enhances the flexibility of the channel layer, enabling it to maintain good transconductance retention even under high periodic stress, allowing the sensor to be applied in wearable devices and other applications. Attached Figure Description

[0023] Figure 1 This is a schematic diagram of the sensor structure provided by the present invention.

[0024] Figure 2 This is a schematic diagram of the gate modification layer structure of the sensor provided by the present invention.

[0025] Figure 3 This is a SEM image of the Prussian blue mediator layer of the sensor provided by the present invention.

[0026] Figure 4 This is a SEM image of the microvascular network within the channel layer of the sensor of the present invention.

[0027] Figure 5 The transfer curves of the sensor of the present invention with different PVA doping ratios when using a PI thin film as a substrate are shown.

[0028] Figure 6 The transfer curves of the sensor of the present invention with different PVA doping ratios when the silicon wafer is used as the substrate are shown.

[0029] Figure 7 This is a comparison diagram of the transconductance of the sensor of the present invention with different PVA doping ratios when using a PI thin film as a substrate.

[0030] Figure 8 This is a comparison diagram of the transconductance of the sensor of the present invention with different PVA doping ratios when the silicon wafer is used as the substrate.

[0031] Figure 9 This is a peak current graph of the sensor of the present invention in glucose solutions of different concentrations.

[0032] Figure 10 The figure shows the bending test results of the sensor of the present invention.

[0033] The attached figures are labeled as follows: 1. Substrate; 2. Bottom electrode; 21. Adhesion layer; 22. Conductive layer; 3. Channel layer; 4. Top electrode; 5. Insulating layer; 6. Gate modification layer; 61. Gate; 62. Prussian blue mediator layer; 621. Gold nanorod; 63. Enzyme complex layer; 64. Protective layer; 100. Detection solution. Detailed Implementation

[0034] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0035] To address the issues of insufficient sensitivity and poor flexibility in existing glucose sensors, this invention provides a vertically structured OECT flexible glucose sensor, as shown in the reference... Figure 1 The sensor is provided with the following components from bottom to top: substrate 1, bottom electrode 2, channel layer 3, top electrode 4, insulating layer 5, and gate modification layer 6.

[0036] Substrate 1 is used to support the entire sensor. Different materials can be selected for substrate 1 depending on the application scenario. For example, silicon wafers can be used when applied to high-precision scenarios, while flexible polyimide (PI) films can be used when applied to wearable devices.

[0037] The bottom electrode 2 is disposed on the upper surface of the substrate 1. A 10nm Cr (chromium) adhesion layer 21 is formed on the side of the bottom electrode 2 in contact with the substrate 1 through thermal evaporation. Its core function is to significantly enhance the interfacial adhesion between the subsequently deposited conductive layer 22 and the substrate 1 material, effectively suppressing and fundamentally eliminating film peeling caused by stress mismatch or interfacial defects, thereby ensuring the structural stability of the device under long-term operation and mechanical deformation. A 50nm Au (gold) conductive layer 22 is formed on the adhesion layer 21 through thermal evaporation. Gold's excellent conductivity, flexibility, and chemical inertness make it an ideal material for electrode fabrication.

[0038] The channel layer 3 is disposed on the upper surface of the conductive layer 22 of the bottom electrode 2 and is in electrical contact with the conductive layer 22. The channel layer 3 is prepared by a high-speed spin coating process using PEDOT:PSS-PVA composite material, and its thickness can be controlled between 50-300nm.

[0039] In the PEDOT:PSS-PVA composite material, the weight fraction of PVA (polyvinyl alcohol) (the weight ratio of PVA to the total weight of PEDOT:PSS+PVA) is less than or equal to 50%, preferably, the weight fraction of PVA is preferably between 16.67% and 50%.

[0040] First, as a flexible polymer, the addition of PVA molecular chains significantly improves the inherent brittleness of the PEDOT:PSS film, endowing the composite channel material with excellent mechanical flexibility. This allows the channel layer 3 to withstand repeated bending and stretching mechanical stresses common in wearable applications without cracking, breaking, or significant degradation of electrical performance, thereby greatly improving the sensor's durability and adaptability.

[0041] Secondly, PVA molecules are rich in hydroxyl groups (-OH), and these hydrophilic groups significantly enhance the surface hydrophilicity and bulk permeability of the PEDOT:PSS-PVA composite membrane. This enhanced hydrophilicity promotes the efficient and uniform penetration of water-soluble electrolytes (such as various ions in sweat, especially H+, the product of GOx reaction) deep into the channel membrane. Efficient ion penetration is crucial for achieving the ion-electron coupling effect in PEDOT:PSS-based OECTs, directly affecting the modulation efficiency of the channel current and the transconductance performance of the device.

[0042] Furthermore, the introduction of PVA induces and assists in a more ordered arrangement and stacking of PEDOT:PSS polymer segments through hydrogen bonding and steric hindrance effects. This ordered arrangement helps optimize the ion transport path and electron transport network within the channel, thereby improving the synergistic efficiency between ion transport and electron transport, ultimately significantly enhancing the overall transconductance performance of the device and making it more sensitive to gate 61 signals.

[0043] Due to its vertical structure, the PEDOT:PSS-PVA composite material can form a nanoscale channel layer 3 through a high-speed spin coating process (spin coating speed 1200 rpm), which effectively shortens the electron channel between the drain and source electrodes (i.e., between the top electrode 4 and the bottom electrode 2). This extremely short electron transport distance significantly accelerates the device's response speed and greatly improves the modulation efficiency of the channel current, thus laying the physical foundation for achieving ultra-high transconductance performance.

[0044] The top electrode 4 is disposed on the upper surface of the channel layer 3 and is in electrical contact with the channel layer 3. A 50nm gold thin film is formed by mask thermal evaporation, which can ensure effective electrical connection with the channel layer 3 and minimize parasitic capacitance and resistance.

[0045] An insulating layer 5 is disposed on the upper surface of the substrate 1, and the channels and contact pads are determined by photolithography.

[0046] A gate modification layer 6 is disposed on the upper surface of the substrate 1 and surrounded by an insulating layer 5. The gate modification layer 6 maintains a certain distance from the channel layer 3 to increase the contact area between the liquid to be detected 100 (i.e., the liquid for which glucose concentration needs to be detected, such as blood or sweat) and the channel layer 3.

[0047] The gate modification layer 6 is provided with a gate 61, a Prussian blue mediator layer 62, an enzyme complex layer 63 and a protective layer 64 from bottom to top.

[0048] The gate 61 is made of the same material as the bottom electrode and the top electrode, which are all gold thin films formed by thermal evaporation process.

[0049] A Prussian blue mediator layer 62 is disposed on the upper surface of the gate 61, and the Prussian blue mediator layer 62 is deposited on the surface of the gate 61 by cyclic voltammetry.

[0050] The enzyme composite layer 63 is fabricated using a mixture of chitosan, graphene, and GOx. Chitosan, as a natural biocompatible polymer, provides a stable microenvironment for GOx enzyme molecules, helping to maintain the enzyme's native conformation and activity. The abundant amino groups (-NH2) in chitosan molecules can form numerous hydrogen bonds and electrostatic interactions with the carboxyl or amino groups on GOx enzyme molecules, effectively assisting in the immobilization of enzyme molecules and preventing their diffusion and loss in solution. Furthermore, the porous gel structure of chitosan provides a three-dimensional channel for the rapid diffusion of glucose substrate and H2O2 product, ensuring the efficiency of the enzymatic reaction. The introduction of graphene is to further enhance the overall performance of the composite layer. Graphene is renowned for its ultra-large specific surface area and excellent conductivity. Its presence in the composite layer significantly increases the effective loading of GOx, thereby improving the sensor's signal output capability. More importantly, graphene's excellent electron transport capability accelerates the electron transfer process between GOx and the Prussian blue mediator layer 62, as well as within the enzyme's active site, further enhancing the sensor's response speed and sensitivity.

[0051] A protective layer 64 covers the enzyme complex layer 63. The protective layer 64 is made of Nafion solution and glutaraldehyde solution. First, a 0.5 wt% Nafion solution is drop-coated onto the upper surface of the enzyme complex layer 63. After drying at room temperature, a 1.2 wt% glutaraldehyde solution is drop-coated to crosslink and fix the enzyme complex layer 63, protecting it from mechanical wear, chemical corrosion or microbial attack, thereby significantly extending the active life of GOx and the overall service life of the sensor.

[0052] Nafion membranes (ion exchange membranes based on perfluorosulfonic acid resin, chemical formula C9HF17O5S, CAS number 31175-20-9) allow small molecule ions (such as enzyme reaction products H2O2 and glucose substrates) to pass freely and efficiently, thereby ensuring the normal progress of enzymatic reactions and effective signal transmission. Nafion membranes effectively block or selectively repel large molecular interferences (such as uric acid, ascorbic acid, and other common biological fluid interferences) or harmful substances that may cause GOx inactivation into the fragile enzyme complex layer 63. This selective permeation capability significantly enhances the selectivity and anti-interference ability of the sensor, thereby improving the accuracy of detection in complex biological samples (such as sweat).

[0053] Glutaraldehyde, as a highly efficient dialdehyde crosslinking agent, contains reactive aldehyde groups at both ends of its molecule. Through precise drop-coating and drying processes, glutaraldehyde molecules can undergo a highly efficient Schiff base reaction with free amino groups (-NH2) present in biomolecules such as GOx enzyme molecules and chitosan. This reaction forms extremely strong covalent bonds, thereby firmly fixing the GOx enzyme molecules and the entire biocomposite matrix therein to the surface of the gate 61. This improves the sensor's adaptability to mechanical stress and complex biological environments, enabling the sensor to be used in wearable devices.

[0054] The flexible glucose sensor with a vertical OECT structure provided by this invention improves the sensor's integration and reduces its size by vertically arranging the drain, source, channel, and gate 61. Simultaneously, the use of PEDOT:PSS-PVA composite material to form a nanoscale flexible channel layer 3 via spin coating enhances the flexibility of the channel layer 3 while reducing its thickness, thereby improving the sensor's response speed and accuracy to meet real-time monitoring requirements. A protective layer 64 is formed on the surface of the enzyme composite layer 63 through crosslinking of a Nafion membrane and glutaraldehyde, improving GOx stability and extending the device's lifespan.

[0055] Furthermore, due to the vertical structure design, the contact area between the channel layer 3 and the gate 61 and the liquid to be detected 100 is reduced. At the same time, since PVA is introduced into the channel layer 3 to improve its various performance characteristics, its drain current also decreases due to the influence of PVA. This leads to a decrease in the signal-to-noise ratio of the acquired signal and increases the difficulty of subsequent signal processing.

[0056] Based on the above phenomena, this application introduces gold nanorods 621 (AuNRs) to improve the Prussian blue mediator layer 62 of the above sensor.

[0057] Specifically, refer to Figure 2When depositing the Prussian blue mediator layer 62 on the upper surface of the gate 61, the gate 61 is modified with APTES ((3-aminopropyl)triethoxysilane) to give the gate 61 a positive electrostatic charge. A gold nanorod CTAB (hexadecyltrimethylammonium bromide) solution is added to the Prussian blue solution, and the gold nanorods 621 are arranged vertically upward through electrostatic adsorption, finally forming gold nanorods 621 perpendicular to the upper surface of the gate 61. Then, Prussian blue is precipitated again to form a mediator layer mixed with Prussian blue and AuNRs.

[0058] The spacing of gold nanorods 621 can be controlled by adjusting the concentration of CTAB in the CTAB solution. After centrifugation and filtration, the concentration of the CTAB solution was controlled at 0.1 mmol·L⁻¹, and the concentration of gold nanorods 621 in the CTAB solution was controlled at 0.05 mg / ml. The sensor prepared under these conditions exhibited good electrochemical performance.

[0059] In actual fabrication, due to limitations in precision (e.g., variations in the concentration of gold nanorods 621, and uneven distribution of positive charge on the upper surface of the gate 61), the crystalline gold nanorods 621 are not strictly perpendicular to the upper surface of the gate 61, but rather partially interleaved, such as... Figure 3 As shown. When the preparation process is properly controlled, this partial interleaving has no significant impact on the sensor's performance.

[0060] Gold nanorods 621 are rod-shaped gold nanoparticles ranging in size from a few nanometers to hundreds of nanometers. Studies have found that gold nanorods 621 and Prussian blue can synergistically enhance the redox reactivity of glucose, thereby increasing the sensitivity of the gate-modified layer 6 to glucose. Specifically, the heterostructure (such as core-shell or supported type) of gold nanorods 621 and Prussian blue shortens the electron transport path, while the cyanide vacancies (VCN) in Prussian blue enhance electronic coupling with gold nanorods 621, lowering the reaction energy barrier.

[0061] The vertical array arrangement of gold nanorods 621 on the upper surface of the gate 61 increases the contact area between the gold nanorods 621 and Prussian blue, enhancing their synergistic effect. Simultaneously, the Prussian blue mediator layer 62 doped with gold nanorods 621 exhibits superior mechanical properties, maintaining good adhesion and stability on the gate 61 and resisting detachment or deformation. This is crucial for fabricating flexible glucose sensors, ensuring accurate glucose concentration detection even under varying bending and stretching conditions. Furthermore, this staggered structure allows for optimization of sensor performance by adjusting the doping ratio and arrangement density of the gold nanorods 621, catering to diverse application requirements.

[0062] Gold nanorods 621 possess high electron mobility and excellent conductivity, enabling rapid electron conduction. Introducing gold nanorods 621 into the Prussian blue mediator layer 62 of the sensor offers several advantages. First, the high conductivity of gold nanorods 621 improves the electron transport performance of the gate 61. Gold nanorods 621 provide more transport channels for electrons, increasing the electron migration rate and thus improving the drain current, ultimately enhancing the strength of the acquired signal. Simultaneously, gold nanorods 621 and the Prussian blue mediator layer 62 can form a synergistic effect. Prussian blue itself has excellent electrocatalytic properties; the interaction between gold nanorods 621 and Prussian blue further optimizes the electrochemical performance of the sensor, resulting in better selectivity and stability when detecting glucose, meeting the requirements for real-time and accurate glucose concentration monitoring.

[0063] Furthermore, since the sensor in this application adopts a vertical OECT structure, when the sensor is bent, the top electrode 4, bottom electrode 2, and channel layer 3 have different elastic moduli, resulting in different deformations. Therefore, relative displacement may occur between the top electrode 4, channel layer 3, and bottom electrode 2, potentially tearing the channel layer 3 and causing vertically extending cracks. This not only alters the contact state between the layers but also changes the transconductance of the channel layer 3, leading to changes in the resistance between the top electrode 4, channel layer 3, and bottom electrode 2. This affects the current between the electrodes, impacting the accuracy and sensitivity of glucose concentration measurement results. In particular, when the relative displacement is large relative to the sensor's scale, it may prevent measurement from being performed.

[0064] Based on the above analysis, during the preparation of channel layer 3, a microvascular network with self-healing function is fabricated within channel layer 3 using laser ablation technology, such as... Figure 4 As shown, DCPD (dicyclopentadiene) crystals and catalysts (such as second-generation Grubbs catalysts or Hoveyda-Grubbs catalysts) are placed within the microvascular network. DCPD has a melting point of 33.6℃, ​​is a crystal at room temperature, and melts into a liquid state when it comes into contact with the human body due to body temperature.

[0065] When a crack appears in channel layer 3, the molten DCPD flows into the crack. The DCPD can undergo a polymerization reaction under the action of a catalyst to generate polydicyclopentadiene, which connects with the hydroxyl groups (-OH) in the PEDOT:PSS-PVA composite material, closing the crack and preventing further crack propagation, thus completing the automatic repair of channel layer 3.

[0066] This self-repair mechanism allows the channel layer 3 to quickly restore its structural integrity after cracking due to external forces such as bending. After recovery, the transconductance of the channel layer 3 stabilizes at a normal level, and the contact state between the top electrode 4, the channel layer 3, and the bottom electrode 2 returns to near-initial optimal conditions, ensuring stable inter-electrode resistance. This allows for stable current transmission within the sensor, significantly improving the accuracy and sensitivity of glucose concentration measurements. Even if the sensor is frequently subjected to complex external forces such as bending during use, as long as there are remaining DCPD crystals and catalysts in the microvascular network, the channel layer 3 can continuously self-repair, effectively extending the sensor's lifespan and reducing sensor failures caused by damage to the channel layer 3.

[0067] Specifically, the microvascular network can be configured as follows: Figure 4 The simple orthogonal grid shown can also be set to other shapes.

[0068] The present invention also provides a method for preparing the above-mentioned sensor, specifically including the following steps:

[0069] 1) Fabrication of substrate 1:

[0070] Clean the silicon wafer or PI film sequentially with acetone, deionized water, and isopropanol, then dry it with nitrogen gas for later use.

[0071] 2) Fabrication of bottom electrode 2:

[0072] On the upper surface of the pretreated substrate 1, a 10 nm Cr thin film (adhesion layer 21) and a 50 nm Au thin film (conductive layer 22) are deposited sequentially from bottom to top using thermal evaporation technology.

[0073] When depositing Cr and Au films, the deposition rate is controlled at approximately 1 Å / s to ensure that the formed Au film has high density, uniform grain size, and minimum defect density, thus guaranteeing the excellent electrical performance and reliability of the bottom electrode 2.

[0074] 3) Preparation of channel layer 3:

[0075] A PEDOT:PSS-PVA mixture was prepared and spin-coated and cured onto the upper surface of the bottom electrode 2 to form a channel layer 3.

[0076] The preparation process of PEDOT:PSS-PVA mixture is as follows:

[0077] S31. Add 5 vol% ethylene glycol, 0.25 vol% DBSA (dodecylbenzenesulfonic acid), and 1 vol% GOPS (trimethoxysilane) to the PEDOT:PSS stock solution and stir until homogeneous.

[0078] In this formulation, ethylene glycol acts as a high-boiling-point solvent and an effective plasticizer. Its role is to finely adjust the rheological properties of the PEDOT:PSS solution, enabling it to form a more uniform and smoother wet film during spin coating. It also helps to improve the microstructure of the PEDOT:PSS film during the subsequent curing process, promotes the orderly arrangement of polymer chains, and thus enhances the conductivity of the final channel layer 3.

[0079] DBSA, as an anionic surfactant, has the core function of significantly reducing the surface tension of the PEDOT:PSS mixture, thereby improving the uniformity of the solution spreading on the substrate 1 surface during spin coating, effectively suppressing the "coffee ring" effect or defects of uneven film thickness, and further optimizing the microstructure of the film, increasing the carrier transport path, which can effectively reduce the thickness of the channel layer 3 and realize the preparation of the nanoscale channel layer 3.

[0080] GOPS, a bifunctional coupling agent with epoxy and trimethoxysilyl groups, functions to achieve chemical crosslinking between PEDOT:PSS molecular chains and potentially subsequent PVA molecular chains. By forming strong covalent bonds, it enhances the mechanical stability and chemical bonding of the composite film at the molecular level, especially its resistance to swelling and degradation in humid environments.

[0081] S32. Dissolve PVA in deionized water (or ultrapure water) and stir until completely dissolved to prepare a 1wt% PVA solution;

[0082] S33. Mix the above PEDOT:PSS blend with PVA solution in proportion to make the PVA weight fraction 16.67%~50%, and magnetically stir at 500 rpm for 3 h to prepare a PEDOT:PSS-PVA mixture with a PVA weight ratio of 16.67%-50% (total weight ratio of PVA to PEDOT:PSS+PVA).

[0083] After preparing the PEDOT:PSS-PVA mixture, the mixture was spin-coated onto the upper surface of the bottom electrode 2 at 1200 rpm for 35 s. After spin-coating, the sample was cured at 130 °C for 1 h to form a PEDOT:PSS-PVA composite film (channel layer 3) with a thickness of 50-300 nm.

[0084] By efficiently evaporating the solvent, the density of the film is ensured, which promotes the further stacking and orderly arrangement of PEDOT:PSS polymer segments. At the same time, it induces and accelerates the crosslinking reaction between PVA, PEDOT:PSS and GOPS, thereby forming a PEDOT:PSS-PVA composite trench membrane with high mechanical strength, excellent electrical properties and the required thickness.

[0085] Furthermore, a microvascular network is prepared within channel layer 3 through the following steps:

[0086] S34. Melt the DCPD at 40°C and dope it with a catalyst (e.g., second-generation Grubbs catalyst or Hoveyda-Grubbs catalyst), with the catalyst mass fraction controlled at 1 wt%-1.5 wt%.

[0087] S35. After spin-coating the PEDOT:PSS-PVA mixture onto the upper surface of the bottom electrode 2 and curing it, spin-coat a water-soluble sacrificial layer (e.g., PVA) with a thickness of 1-2 μm onto the surface of the channel layer 3.

[0088] S36. Microchannels with a preset pattern are ablated on the channel layer 3 by laser ablation technology, and DCPD is melted at 40°C and then drop-coated onto the channel layer 3 under vacuum.

[0089] S37. Cool the DCPD at room temperature to allow it to crystallize within the microchannel, forming a DCPD crystal doped with the catalyst.

[0090] S38. Clean the channel layer 3 with low-temperature (below 20°C) deionized water to remove the water-soluble sacrificial layer and the DCPD crystals attached thereto, while retaining the DCPD crystals in the microchannel.

[0091] S39. Spin-coat the PEDOT:PSS-PVA mixture again and heat it at 130℃ for 1 hour to complete the preparation of the microvascular network.

[0092] 4) Fabrication of top electrode 4:

[0093] The top electrode 4 region is defined using a shadow mask, and a 50nm Au thin film is deposited on the upper surface of the channel layer 3 by thermal evaporation to form the top electrode 4.

[0094] 5) Preparation of insulating layer 5:

[0095] SU-82000 photoresist is spin-coated on the upper surface of substrate 1. Photolithography is used to remove the photoresist on the channels and contacts (electrode contacts, including bottom electrode 2 and top electrode 4), so that there is a 100 μm / 100 μm channel between the gate modification layer 6 and the channel layer 3 that can accommodate the test liquid 100. A portion of the photoresist is retained around the gate 61 and the channel layer 3 as an insulating layer 5.

[0096] 6) Fabrication of gate modification layer 6:

[0097] On the upper surface of substrate 1, from bottom to top, a gate 61, a Prussian blue mediator layer 62, an enzyme complex layer 63, and a protective layer 64 are formed sequentially, ultimately forming a gate modification layer 6.

[0098] The fabrication process of gate 61 is similar to that of bottom electrode 2 and top electrode 4, that is, an Au thin film is formed on the upper surface of substrate 1 by thermal evaporation technology.

[0099] Prussian blue mediator layer 62 was prepared using the following steps:

[0100] Prussian blue was deposited on the surface of an Au electrode (gate 61) by cyclic voltammetry (0–0.5 V vs Ag / AgCl, scan rate 20 mV / s, 1 cycle) in a mixture of 2.5 mmol·L⁻¹ FeCl₃, 10 mmol·L⁻¹ KCl solution, 2.5 mmol·L⁻¹ K₃Fe(CN)₆ and 100 mmol·L⁻¹ HCl.

[0101] Furthermore, during the preparation of the Prussian blue mediator layer 62, a Prussian blue mediator layer 62 doped with gold nanorods 621 was formed. The specific preparation process is as follows:

[0102] S65. Clean the upper surface of gate 61. Immerse the upper surface of gate 61 in an ethanol or toluene solution with an APTES concentration of 0.5 vol% to 1 vol% for 30 minutes, then clean the upper surface of gate 61 and dry it with nitrogen gas. This allows APTES molecules to form a self-assembled monolayer (SAM) on the upper surface of gate 61. The amino groups (-NH2) at the ends of the SAM will be protonated under neutral or weakly acidic conditions, thereby giving the entire upper surface of gate 61 a positive charge.

[0103] S66. Preparation of gold nanorod CTAB solution: Add gold nanorods to a CTAB solution with a concentration of 0.08-0.12 mmol·L-1 to make the concentration of gold nanorods 0.03-0.05 mg / ml.

[0104] S67. Soak the upper surface of the gate 61 in a gold nanorod CTAB solution at room temperature or slightly higher temperature (30-40℃) for more than 12 hours, so that the positively charged upper surface of the gate 61 adsorbs the negatively charged gold nanorods coated with CTAB, forming vertically grown gold nanorods 621.

[0105] S68. Slowly clean the upper surface of the gate 61 with deionized water, and slowly dry it with nitrogen or let it air dry at room temperature.

[0106] S69. Treat the upper surface of gate 61 with cysteine ​​and PVP (polyvinylpyrrolidone) to replace the CTAB encapsulating the gold nanorods, exposing the gold nanorods 621.

[0107] Prepare a 1-5 mmol·L⁻¹ aqueous solution of cysteine, adjust the pH to 3.0-4.0, and soak the upper surface of the gate 61 at room temperature for 2-4 h. This allows the thiol groups of cysteine ​​to form a strong gold-sulfur (Au-S) covalent bond with the surface of the gold nanorod 621, thereby displacing CTAB molecules. Then, slowly rinse the gate 61 with deionized water (ultrapure water) to remove the detached CTAB and free cysteine. Subsequently, immerse the gate 61 in a 0.5-1 mg / mL PVP aqueous solution and incubate at room temperature for at least 1 h. PVP molecules further stabilize the nanorods through the weak interaction between their carbonyl groups and the gold surface, as well as physical encapsulation, forming a more hydrophilic and inert interface. Finally, slowly rinse the gate 61 again with deionized water (ultrapure water) to remove the PVP adhering to the surface of the gold nanorod 621, and dry with nitrogen gas.

[0108] S610, Prussian blue was deposited on the surface of the Au electrode (gate 61) by cyclic voltammetry (0~0.5 V vs Ag / AgCl, scan rate 20 mV / s, 1 cycle) in a mixture containing 2.5 mmol·L⁻¹ FeCl₃, 10 mmol·L⁻¹ KCl solution, 2.5 mmol·L⁻¹ K₃Fe(CN)₆ and 100 mmol·L⁻¹ HCl.

[0109] Gold nanorods 621 are vertically adsorbed onto the upper surface of gate 61 through an electrostatic adsorption process. During the cleaning and drying process, the flow rate of water and air is controlled to avoid damaging the vertical array of gold nanorods 621, thereby ensuring a good doping configuration of gold nanorods 621 and Prussian blue mediator layer 62.

[0110] Enzyme complex 63 was prepared using the following steps:

[0111] S61. Dissolve chitosan in 2wt% acetic acid to obtain a 1wt% chitosan solution;

[0112] S62. The chitosan solution and the 2 mg / ml graphene solution were ultrasonically mixed for 10 h to obtain a chitosan-graphene mixed solution.

[0113] S63. Dissolve GOx in PBS (phosphate buffer) solution with pH=7.5 and a concentration of 1 mmol / L to form a GOx solution with a concentration of 10 mg / ml;

[0114] S64. Mix the chitosan-graphene mixed solution with the GOx solution at a volume ratio of 2:1, drop-coat the mixture onto the Prussian blue mediator layer 62, and dry at room temperature.

[0115] The protective layer 64 is made of Nafion solution and glutaraldehyde solution. First, a 0.5 wt% Nafion solution is dropped onto the upper surface of the enzyme complex layer 63. After drying at room temperature, a 2 wt% glutaraldehyde solution is dropped onto the surface to crosslink and fix the enzyme complex layer 63.

[0116] The sensor provided in this application is fabricated by following the steps described above.

[0117] To verify the electrochemical performance of the sensor provided by this invention, electrochemical characterization was performed. A Keithley 2602B source meter was used for testing, and the output curve scan ranged from -0.1 to 0.9 V (drain voltage -0.6 V), while the transfer curve showed a fixed drain voltage of -0.6 V (gate voltage -0.1 to 0.9 V).

[0118] Figure 5 The transfer curve of the sensor prepared on a PI thin film substrate 1 is shown. Figure 6 The transfer curve of the sensor fabricated on a silicon wafer substrate 1 is shown.

[0119] As shown in the figure, the use of different substrate materials has a significant impact on the transfer curve of the sensor. The slope of the transfer curve of the sensor with silicon wafer substrate 1 is greater than that of the PI thin film substrate 1, indicating that the silicon wafer substrate 1 has better electrochemical performance.

[0120] Meanwhile, the glucose sensors prepared with different PVA doping ratios of PEDOT:PSS-PVA composite materials exhibited different transfer curves. As the proportion of PVA in the PEDOT:PSS-PVA composite material increased, the transfer curve continuously decreased. The slope of the conduction segment in the transfer curve of the undoped PEDOT:PSS material was significantly smaller than that of the PVA-doped PEDOT:PSS material, indicating that PVA doping significantly improves the electrochemical performance of PEDOT:PSS.

[0121] Figure 7 The transconductance comparison diagram of the sensor prepared on PI film as substrate 1 is shown. It can be seen from the figure that when the weight ratio of PVA doping is 37.5%, the transconductance of channel layer 3 is the largest, and its peak value is significantly higher than that of other PVA doping ratios.

[0122] Figure 8 The transconductance comparison diagram of the sensor fabricated on silicon wafer substrate 1 is shown. It can be seen that the transconductance of the sensor has a significant peak when the doping ratio of PVA is also 37.5%.

[0123] Figure 9 This is a peak current graph of the sensor of the present invention in glucose solutions of different concentrations. It can be seen that after the Prussian blue mediator layer 62 is doped with gold nanorods 621, the curve of the relationship between the drain current and the glucose concentration is generally higher than that of the mediator layer without gold nanorods 621, and the slope is significantly increased. It can be seen that gold nanorods 621 have a significant effect on increasing the drain current and improving the sensor's response sensitivity to glucose.

[0124] Figure 10 The bending experiment results of the sensor provided by this invention are shown. Bending experiments were performed on sensors without a microvascular network in the channel layer 3 and sensors with a microvascular network in the channel layer 3, respectively. The bending radius was 5 mm. After different numbers of bends, the transconductance of the sensor was measured with a 50 μM glucose solution. The sensor used in this experiment is based on a PI thin film substrate 1 with a PVA doping ratio of 37.5%. Figure 10 It is evident that the transconductance of the sensor without a microvascular network in the channel layer 3 decreased significantly after 2000 bending tests, while the transconductance of the sensor with a microvascular network began to decrease slowly after 1500 bending tests, and only began to decrease rapidly after 3500 bending tests. This shows that the vascular network effectively improved the lifespan of the sensor.

[0125] In conclusion, the above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A vertical structure OECT flexible glucose sensor, characterized in that, include: Substrate; A bottom electrode is disposed on the upper surface of the substrate, and an adhesive layer is disposed on the side of the bottom electrode that contacts the substrate, and a conductive layer is disposed on the upper surface of the adhesive layer; A channel layer is disposed on the upper surface of the conductive layer of the bottom electrode and is in electrical contact with the conductive layer. The channel layer is composed of PEDOT:PSS-PVA composite material. A top electrode is disposed on the upper surface of the channel layer and is in electrical contact with the channel layer; An insulating layer is disposed on the upper surface of the substrate; A gate modification layer is disposed on the upper surface of the substrate, and an insulating layer is disposed around the gate modification layer; The gate modification layer is provided from bottom to top with a gate, a Prussian blue mediator layer, an enzyme complex layer and a protective layer; In the PEDOT:PSS-PVA composite material, the weight fraction of PVA is 16.67% to 50%. The channel layer is provided with a microvascular network, which is filled with DCPD and catalyst to repair cracks in the channel layer. The Prussian blue mediator layer contains gold nanorods perpendicular to the upper surface of the gate.

2. The sensor of claim 1, wherein, The enzyme complex layer in the gate modification layer is a composite layer of GOx, chitosan, and graphene. The enzyme complex layer is prepared by the following steps: Chitosan was dissolved in 2 wt% acetic acid to obtain a 1 wt% chitosan solution; Chitosan solution was ultrasonically mixed with 2 mg / ml graphene solution for 10 h to obtain chitosan-graphene mixed solution; GOx was dissolved in a PBS solution with a pH of 7.5 and a concentration of 0.001 mol / L to form a GOx solution with a concentration of 10 mg / ml; The chitosan-graphene mixture was mixed with the GOx solution at a volume ratio of 2:1, and then drop-coated onto the Prussian blue mediator layer and dried at room temperature.

3. A method of manufacture for the manufacture of a sensor according to any one of claims 1-2, c h a r a c t e r i s e d in that, Includes the following steps; The substrate is cleaned and dried. A bottom electrode is formed by depositing a chromium thin film and a gold thin film sequentially from bottom to top on the upper surface of the substrate using thermal evaporation technology. A PEDOT:PSS-PVA mixture was prepared and spin-coated and cured onto the upper surface of the bottom electrode to form a channel layer. The top electrode region is defined using a shadow mask, and a gold thin film is deposited on the upper surface of the channel layer using a thermal evaporation process to form the top electrode; Photoresist is spin-coated onto the upper surface of the top electrode, and photolithography is used to remove the photoresist on the channels and contacts, leaving a portion of the photoresist as an insulating layer. A gate, a Prussian blue mediator layer, an enzyme complex layer, and a protective layer are sequentially formed from bottom to top on the upper surface of the substrate, ultimately forming a gate modification layer.

4. The production method according to claim 3, characterized by, The PEDOT:PSS-PVA mixture was prepared using the following steps: Add 5 vol% ethylene glycol solution, 0.25 vol% DBSA solution and 1 vol% GOPS solution to the PEDOT:PSS stock solution and stir until homogeneous; Dissolve PVA in deionized water and stir until completely dissolved to prepare a 1wt% PVA solution; The above PEDOT:PSS blend and PVA solution were mixed in proportion to make the PVA weight fraction 16.67%~50%, and the mixture was magnetically stirred at 500 rpm for 3 h to prepare the PEDOT:PSS-PVA mixture.

5. The preparation method according to claim 4, characterized in that, The PEDOT:PSS-PVA mixture is spin-coated onto the upper surface of the bottom electrode using the following steps: The PEDOT:PSS-PVA mixture was spin-coated onto the upper surface of the bottom electrode at 1200 rpm for 35 s. The mixture was then cured at 130 °C for 1 h to form a PEDOT:PSS-PVA composite film.

6. The production method according to claim 5, wherein A microvascular network is prepared within the channel layer using the following steps: DCPD was melted at 40°C and doped with a catalyst, the mass fraction of which was controlled at 1 wt%-1.5 wt%. A water-soluble sacrificial layer with a thickness of 1-2 μm is spin-coated onto the surface of the channel layer; Microchannels with a pre-designed pattern are ablated on the channel layer using laser ablation technology, and DCPD molten at 40°C is drop-coated onto the channel layer under vacuum. Cooling at room temperature allows DCPD to crystallize within the microchannel, forming DCPD crystals doped with the catalyst. Clean the channel layer with deionized water at a temperature below 20°C; The PEDOT:PSS-PVA mixture was spin-coated again and cured at 130℃ for 1 hour to complete the preparation of the microvascular network.

7. The preparation method according to claim 3, characterized in that, The enzyme complex layer is prepared by the following steps: Chitosan was dissolved in 2 wt% acetic acid to obtain a 1 wt% chitosan solution; Chitosan solution was ultrasonically mixed with 2 mg / ml graphene solution for 10 h to obtain chitosan-graphene mixed solution; GOx was dissolved in a PBS solution with a pH of 7.5 and a concentration of 0.001 mol / L to form a GOx solution with a concentration of 10 mg / ml; The chitosan-graphene mixture was mixed with the GOx solution at a volume ratio of 2:1, and then drop-coated onto the Prussian blue mediator layer and dried at room temperature.

8. The preparation method according to claim 3, characterized in that, A protective layer is formed on the upper surface of the enzyme complex layer through the following steps: A 0.5 wt% Nafion solution was drop-coated onto the upper surface of the enzyme composite layer. After drying at room temperature, a 2 wt% glutaraldehyde solution was drop-coated onto the surface to crosslink and fix the enzyme composite layer.

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