Optoelectronic microneedle glucose monitoring sensor

Abstract

An enzyme-free photoelectric microneedle blood glucose sensor includes a flexible substrate, a conductive electrode layer, a microneedle array, an enzyme-free photoelectric sensing layer, a hydrogel anti-interference layer, and a miniature light source / photoelectric signal acquisition module. First, BiVO4 photocatalyst and MXene two-dimensional conductive material are prepared and composited into a BiVO4-MXene composite material, with FeCoO2 loaded onto it. x BiVO4-MXene-FeCoO x A ternary heterojunction material is used to form a hydrogel anti-interference layer inside a microneedle array, which is then integrated with a conductive electrode layer, a flexible substrate, and a photoelectric signal acquisition module. The ternary heterojunction material, along with the microneedle matrix material, conductive components, and gel, is filled into a microneedle mold, cured, dried, and cross-linked before demolding. The design is scientifically sound, the preparation method is easy to operate, it eliminates dependence on biological enzymes, and exhibits strong stability. It also boasts high sensitivity, high charge separation efficiency, strong anti-interference ability, minimal invasiveness and low pain, and is easy to scale up, making it valuable for practical application.

Description

Technical Field

[0001] This invention relates to the field of in vitro biosensing technology, particularly based on BiVO4-MXene-FeCoO4. x A photoelectric microneedle glucose monitoring sensor based on a ternary heterojunction. Background Technology

[0002] People with diabetes and abnormal glucose metabolism require long-term, frequent access to glucose level information to support diet, exercise, medication, and hypoglycemia risk management. Current blood glucose testing technologies mainly include finger-prick blood glucose meters and continuous glucose monitoring systems (CGM). The former typically requires pricking a finger and relies on disposable test strips, which has drawbacks such as pain, inconsistent data, and difficulty reflecting 24-hour fluctuations. The latter can continuously monitor tissue fluid glucose, but it often uses subcutaneously implanted sensor probes, which may still present problems such as foreign body sensation, discomfort, high cost, and a high barrier to entry for use. Therefore, blood glucose monitoring has become a crucial infrastructure for chronic disease management.

[0003] From a sensing mechanism perspective, most commercial glucose detection sensors rely on biological enzymes such as glucose oxidase or glucose dehydrogenase. Enzyme-based sensors have the advantage of good selectivity, but enzyme activity is easily affected by temperature, pH, humidity, storage environment, and long-term use, which may lead to problems such as enzyme inactivation, response drift, and shortened lifespan. Although enzyme-free sensors can avoid enzyme inactivation, some enzyme-free electrochemical materials suffer from insufficient sensitivity, weak anti-interference ability, and insufficient stability in complex biological matrices.

[0004] Photoelectrochemical sensing technology combines photoexcitation with electrical signal readout, possessing the potential for low background noise and high sensitivity. BiVO4 is a class of semiconductor photocatalytic materials with visible light response capabilities; however, the photogenerated electron-hole pairs in single BiVO4 readily recombine, limiting charge utilization efficiency and sensing response intensity. MXene two-dimensional materials possess high conductivity and abundant surface functional groups, serving as electron extraction and transport channels; FeCoO4... x (x=2~4) exhibits good hole trapping and catalytic oxidation capabilities, which can promote glucose oxidation. However, how to synergistically construct a stable, efficient, and low-interference sensing system on the microneedle interface, and further realize the integration of minimally invasive devices for tissue fluid detection, remains an urgent problem to be solved.

[0005] Therefore, it is necessary to provide a photoelectric microneedle glucose monitoring sensor and its preparation method that does not require biological enzymes, can directly contact tissue fluid, has high charge separation efficiency, strong anti-interference ability and minimally invasive wearing comfort, but no public reports have been found to date. Summary of the Invention

[0006] In view of the above situation and to overcome the shortcomings of the prior art, the purpose of this invention is to provide an enzyme-free photoelectric microneedle blood glucose sensor, which aims to solve the problems of existing enzyme-based glucose sensors being easily deactivated by environmental influences, insufficient sensitivity and anti-interference ability of traditional enzyme-free sensors, high carrier recombination rate of single photocatalytic materials, and the foreign body sensation and high cost of existing continuous glucose monitoring devices.

[0007] The technical solution provided by this invention is: an enzyme-free photoelectric microneedle blood glucose sensor, comprising a flexible substrate 3, a conductive electrode layer 4 supported on the flexible substrate 3, a microneedle array 1 connected to the conductive electrode layer 4 and used for contacting subcutaneous tissue fluid, an enzyme-free photoelectric sensing layer 1-2 loaded on the surface of the microneedle array 1, a hydrogel anti-interference layer 2 covering the microneedle array 1, and a connecting micro-light source / photoelectric signal acquisition module 5 connected to the conductive electrode layer 4; wherein, the enzyme-free photoelectric sensing layer 1-2 comprises BiVO4, MXene two-dimensional conductive material and FeCoO4. x The BiVO4, MXene and FeCoO x Together, they form a ternary heterojunction for enzyme-free photoelectrocatalytic oxidation detection of glucose, where x = 2~4, and Fe and Co are mainly Fe. 3+ and Co 3+ It also contains Fe-O-Co bonds; Its preparation method includes the following steps: 1) BiVO4 photocatalyst materials were prepared by hydrothermal synthesis or electrodeposition. 2) MXene two-dimensional conductive material was prepared by etching with hydrofluoric acid and lithium fluoride, and then the MXene two-dimensional conductive material was combined with BiVO4 to form BiVO4-MXene composite material; 3) FeCoO2 was loaded onto the surface of BiVO4-MXene composite material by spin coating via dip-coating, electrodeposition, and photodeposition. x BiVO4-MXene-FeCoO x Ternary heterojunction materials; 4) A hydrogel anti-interference layer is formed inside the microneedle array and integrated with the conductive electrode layer, flexible substrate and photoelectric signal acquisition module; 5) The ternary heterojunction material, microneedle matrix material, conductive components and gel are filled into a microneedle mold, and after curing, drying and cross-linking, the mold is demolded to obtain the photoelectric microneedle glucose monitoring sensor.

[0008] This invention is scientifically and rationally designed, with an easy-to-operate preparation method that eliminates dependence on biological enzymes, exhibits strong stability, high sensitivity, high charge separation efficiency, strong anti-interference ability, minimally invasive and painless operation, and is easy to prepare on a large scale, thus having practical application value. Attached Figure Description

[0009] Figure 1 This is a schematic diagram of the structure of the enzyme-free photoelectric microneedle blood glucose sensor of the present invention; Figure 2 This is an enlarged view of the structure of the microneedle of the present invention; Figure 3 This is a flowchart illustrating the fabrication process of the enzyme-free photoelectric microneedle blood glucose sensor of the present invention. Figure 4 The present invention is BiVO4-MXene-FeCoO x The current response curves of the composite material at different glucose concentrations are used to characterize the sensor's ability to respond to changes in glucose concentration. Figure 5 This is a comparison chart of the test results of the enzyme-free photoelectric microneedle blood glucose sensor of the present invention and a commercially available blood glucose meter, used to verify the accuracy and reliability of the sensor's detection results. Figure 6 The present invention is BiVO4-MXene-FeCoO x Linear sweep voltammetry curves of composite materials under different loading levels are used to compare the effects of different material loading levels on photoelectric response performance. Detailed Implementation

[0010] The specific embodiments of the present invention will be described in detail below with reference to the accompanying drawings and specific circumstances.

[0011] Depend on Figure 1-2 The present invention discloses a photoelectric microneedle glucose monitoring sensor, characterized in that it comprises a flexible substrate 3, a conductive electrode layer 4 supported on the flexible substrate 3, a microneedle array 1 connected to the conductive electrode layer 4 and used for contacting subcutaneous tissue fluid, an enzyme-free photoelectric sensing layer 1-2 loaded on the surface of the microneedle array 1, a hydrogel anti-interference layer 2 covering the microneedle array 1, and a connecting micro-light source / photoelectric signal acquisition module 5 connected to the conductive electrode layer 4; wherein, the enzyme-free photoelectric sensing layer 1-2 comprises BiVO4, MXene two-dimensional conductive material and FeCoO4. x The BiVO4, MXene and FeCoO x Together, they form a ternary heterojunction for enzyme-free photoelectrocatalytic oxidation detection of glucose, where x = 2~4, and Fe and Co are mainly Fe. 3+ and Co 3+ It also contains Fe-O-Co bonds.

[0012] The BiVO4 is monoclinic scheelite phase BiVO4 nanoparticles; the MXene is Ti3C2T x T xThe variable end groups on the Ti3C2 surface mainly include one or more of -O, -OH, and -F; the FeCoO x This is a simplified expression for Fe-Co oxide / hydroxy oxide composite cocatalyst.

[0013] In the enzyme-free photosensitive layer, the mass percentage of MXene relative to BiVO4 is 10%-25%, and FeCoO4 is... x The loading relative to the BiVO4-MXene complex is 1%-10%.

[0014] BiVO4, as a visible-light-responsive photocatalytic active substrate, generates electron-hole pairs under illumination; MXene, as a two-dimensional conductive material, forms a tight interfacial contact with BiVO4 to extract and transport photogenerated electrons, reducing the probability of electron-hole recombination; FeCoO4... x Loaded on the surface or interface region of BiVO4-MXene composite materials, these components capture migrating holes and promote glucose oxidation. Together, they form a ternary heterojunction, enhancing the separation efficiency of photogenerated carriers and the intensity of the glucose oxidation signal at the material interface.

[0015] The microneedle array comprises multiple evenly distributed microneedles, all of which are hollow or coated microneedles, with a height of 200-1200 μm, a tip curvature radius of less than 50 μm, and a center-to-center distance of 300-1500 μm between adjacent microneedles. The microneedles are composed of an outer anti-interference hydrogel 2-1, an inner anti-interference hydrogel 2-2, a microneedle substrate 1-1, and an enzyme-free photoelectric sensing layer 1-2. The microneedle substrate 1-1 is made of a biocompatible polymer material, which is selected from one or a mixture of multiple materials in any mass ratio from chitosan, carboxymethyl chitosan, hyaluronic acid, sodium alginate, gelatin, gelatin methacrylamide, polyvinyl alcohol, polyvinylpyrrolidone, polyethylene glycol polymers, and 2-methacryloyloxyethyl phosphocholine polymers.

[0016] The hydrogel anti-interference layer 2 is disposed at the tip region of the microneedle array, the outer side of the enzyme-free photoelectric sensing layer, or a combination of the above regions. It is formed of an anti-sewage gel material selected from one or more of chitosan, carboxymethyl chitosan, hyaluronic acid, sodium alginate, gelatin, polyvinyl alcohol, polyethylene glycol polymers, polyvinylpyrrolidone, 2-methacryloyloxyethyl phosphocholine polymers, sulfobetaine polymers, and carboxybetaine polymers. The hydrogel anti-interference layer is used to reduce the influence of proteins, uric acid, ascorbic acid, lactic acid, sweat components, or other reducing substances on the glucose detection signal. The conductive electrode layer 4 includes one or a mixture of multiple materials in any mass ratio selected from gold, platinum, silver / silver chloride, carbon materials, graphene, MXene, or conductive polymers.

[0017] The photoelectric signal acquisition module 5 includes a miniature light source, a current acquisition unit, an analog-to-digital conversion unit, a data processing unit, and a wireless communication unit. The miniature light source can be an LED or a miniature laser, with an emission wavelength preferably between 400-470 nm. The data processing unit can convert changes in photocurrent into tissue fluid glucose concentration or glucose change trends based on a calibration curve.

[0018] The fabrication method of the photoelectric microneedle glucose monitoring sensor includes the following steps: 1) BiVO4 photocatalyst materials were prepared by hydrothermal synthesis or electrodeposition. 2) MXene two-dimensional conductive material was prepared by etching with hydrofluoric acid and lithium fluoride, and then the MXene two-dimensional conductive material was combined with BiVO4 to form BiVO4-MXene composite material; 3) FeCoO2 was loaded onto the surface of BiVO4-MXene composite material by spin coating via dip-coating, electrodeposition, and photodeposition. x BiVO4-MXene-FeCoO x Ternary heterojunction materials; 4) A hydrogel anti-interference layer is formed inside the microneedle array and integrated with the conductive electrode layer, flexible substrate and photoelectric signal acquisition module; 5) The ternary heterojunction material, along with the microneedle matrix material, conductive components, and gel, are filled into a microneedle mold. After curing, drying, and cross-linking, the mold is demolded to obtain the photoelectric microneedle glucose monitoring sensor. For example... Figure 4 The current response curves of the composite material at different glucose concentrations show that the sensor has a clear response to glucose. The current-time curve obtained by fitting the data shows a correlation of 0.98, indicating that it has good linear response capability to glucose concentration. Figure 3 The BiVO4-MXene-FeCoO x The specific preparation method of ternary heterojunction materials is as follows: 1) Preparation of BiVO4 electrode: The electrode was first prepared by electrodeposition to form a BiOI electrode precursor film, thus creating a nanoporous BiVO4 electrode. A typical plating solution was 50 mL of an aqueous solution containing 0.04 M Bi(NO3)3·5H2O and 0.4 M KI. The pH was adjusted to 1.7 by adding nitric acid. Then, 20 mL of an ethanol solution containing 0.23 M p-benzoquinone was slowly added to induce the precipitation of BiOI in the solution. The mixture was stirred for several minutes until the pH stabilized. Electrodeposition was performed using a typical three-electrode system: a fluorine-doped tin oxide (FTO) working electrode (WE), an Ag / silver chloride reference electrode (RE), and a platinum counter electrode (CE). Cathodic deposition was performed at a constant potential of -0.1 V relative to Ag / silver chloride at room temperature, with an adjustable deposition time (2.5–5 min). The resulting BiOI electrode was then obtained. 200 μL of a 0.2 M acetylacetonate vanadate solution in dimethyl sulfoxide (DMSO) was added dropwise to a BiOI electrode. The BiOI electrode was then heat-treated in air at 450°C for 2 h (heating rate 2°C / min) to convert it to BiVO4. After conversion, excess vanadium pentoxide in the BiVO4 electrode was removed by immersing the membrane in a 1 M sodium hydroxide solution with stirring (approximately 350 rpm / min) for 30 min. The electrode was then thoroughly rinsed with deionized water and dried with an airflow, and labeled as BiVO4.

[0019] 2) MXene loaded onto BiVO4: 40 mL of hydrochloric acid solution (36-38%) and 3.2 g of lithium fluoride were added to a polytetrafluoroethylene-lined stainless steel autoclave and stirred thoroughly for 15 min. 2.0 g of Ti3AlC2 precursor powder was gently added to the lithium fluoride / hydrochloric acid solution, and etching was performed at 35°C for 48 h. The etched black turbid substance was centrifuged at 3500 rpm for 5 min, washed with deionized water, and the process was repeated until pH > 6. After centrifugation, the supernatant gradually turned black; repeated washing was performed until the solid was fluffy, yielding a supernatant containing exfoliated MXene nanosheets. An aqueous MXene solution (aq) was dropped onto the film of the BiVO4 sample, and spin-coated at 2000 rpm / min for 30 seconds. Multiple BiVO4-MXene photodetectors were prepared by adding different concentrations of MXene (aq). Subsequently, an annealing step was used to enhance the interaction between FTO, BiVO4, and MXene. The BiVO4-MXene film was annealed at 300°C for 30 min in an argon atmosphere. Finally, a BiVO4-MXene sample was obtained.

[0020] 3) FeCoO x Deposition: Fe precursor solution: Accurately weigh 0.1 mol / L Fe(SO4)2·7H2O, dissolve and dilute with deionized water, stir for 30 min until completely dissolved, ensuring the solution is homogeneous and transparent without precipitation.

[0021] Co precursor solution: Prepare 25×10 -3 Prepare a mol / L (25 mM) aqueous solution of (CH3COO)2Co·4H2O, stir for 20 min until clear, and seal for later use.

[0022] A FeOOH layer was deposited in a 0.1 M Fe(SO4)2·7H2O solution at a voltage of 0.25 V for 5 min. Then, a 25 × 10⁻⁶ layer was deposited. -3 CoO deposited in M ​​(CH3COO)2Co·4H2O solution x The voltage was 0.25 V and the reaction time was 40 s.

[0023] 4) Preparation of the hydrogel anti-interference layer: Take 10.0 mL of 2% carboxymethyl chitosan solution and place it in a 50 mL three-necked round-bottom flask, operating in the dark throughout the process. Calculate and weigh 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide, based on 1.2 times the total molar amount of amino groups on the chitosan molecule, maintaining a strict molar ratio of 2:1. First, add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride to the system and stir for 5 min until completely dissolved. Then, add N-hydroxysuccinimide. Purge the flask with high-purity nitrogen for 10 min to purge all air from the flask. Seal the flask and stir continuously at 200 rpm for 30 min at room temperature in the dark to activate the carboxyl sites of the chitosan.

[0024] Accurately weigh 0.040 g of 2-methacryloxyethylphosphocholine monomer at a mass ratio of 1:5 (2-methacryloxyethylphosphocholine to chitosan) and add it to the activated chitosan solution. Purge with high-purity nitrogen for 10 min to purge air from the system. Seal the three-necked flask and stir continuously at 200 rpm for 24 h at room temperature in the dark. After the reaction, a crude product solution is obtained, which needs to be purified: place the crude product solution into a pre-treated dialysis bag and clamp both ends with dialysis clamps to ensure no leakage. Place the dialysis bag in a beaker containing 2 L of deionized water and dialyze at room temperature in the dark. Replace the deionized water every 6 h and continue dialysis for 3 days to completely remove unreacted 2-methacryloxyethylphosphocholine monomer, residual activating reagent, and small molecule byproducts from the system. After dialysis, the solution in the dialysis bag was removed and concentrated at 35°C using a vacuum rotary evaporator. The solid content was calibrated by drying to constant weight until the solid content of the solution stabilized at 2% by mass, yielding a purified 2-methacryloyloxyethyl phosphorocholine-grafted carboxymethyl chitosan solution, which was stored at 4°C in the dark and sealed. 10.0 mL of a 10% by mass polyvinyl alcohol stock solution and 10.0 mL of a 2% by mass 2-methacryloyloxyethyl phosphorocholine-grafted carboxymethyl chitosan solution were added to a 50 mL centrifuge tube, with a strict volume ratio of 1:1. The mixture was stirred continuously at 300 rpm for 30 min at room temperature until the two solutions were completely mixed and the system was homogeneous and transparent, without layering or flocculent matter. The procedure is performed in a fume hood: A 2.5% (w / w) aqueous solution of glutaraldehyde is added dropwise to the well-mixed solution. The final amount of glutaraldehyde is 1%–1.5% of the total volume of the mixture (e.g., 0.2–0.3 mL of 2.5% glutaraldehyde solution is needed for 20 mL of mixture). The mixture is continuously and rapidly stirred during the addition process, and stirred for another 1 min after the addition is complete to ensure complete dispersion of the crosslinking agent. The resulting composite hydrogel precursor sol should be prepared and used immediately. Within 30 min of preparation, the slurry should be coated and molded into a microneedle mold, and centrifugation should be used to facilitate the slurry's entry into the needle tip region. Drying is then performed to form the microneedle array. A microneedle array containing an enzyme-free photosensitive layer is obtained.

[0025] 5) Fabrication of photoelectric microneedle array: The microneedle array is assembled with a flexible substrate, a conductive electrode layer, an encapsulation layer, a micro light source, and a signal acquisition module. The flexible substrate can be made of polyimide, polyethylene terephthalate, polydimethylsiloxane, or medical adhesive materials.

[0026] Application of the photoelectric microneedle glucose monitoring sensor in tissue fluid glucose detection and blood glucose trend monitoring.

[0027] Application of the photoelectric microneedle glucose monitoring sensor in blood glucose abnormality risk warning.

[0028] Application of the photoelectric microneedle glucose monitoring sensor in chronic disease management devices or wearable health monitoring devices.

[0029] It should be noted that the embodiments given above are merely for illustrating specific implementations of the present invention, and are not intended to limit the scope of protection of the present invention. Any technical solutions that are essentially the same as those made using equivalent substitutions are within the scope of protection of the present invention. For example: 1. BiVO4 can replace or be combined with other visible light responsive semiconductor materials, such as WO3, TiO2 modified materials, ZnO modified materials, or other bismuth-based semiconductor materials, as long as they can react with MXene and FeCoO. x A composite interface is formed that is conducive to the separation of photogenerated carriers.

[0030] 2. FeCoO x It can be replaced with transition metal oxides, hydroxides, or hydroxyl oxides containing iron, cobalt, nickel, manganese, copper, etc., and can also be combined with FeCoO x Together they constitute a multi-metal catalytic unit.

[0031] 3. The microneedle array can be a disposable consumable or a separate structure with a reusable light source and signal reading module; after the microneedle consumable is replaced, it can be connected to the reading module by plug-in, magnetic attraction or flexible ribbon cable.

[0032] 4. The hydrogel anti-interference layer can simultaneously serve as a tissue fluid collection, buffer, pre-filtration, and skin adhesion layer. It can also be combined with drug release, anti-inflammatory and soothing, or antibacterial components to adapt to long-term wear.

[0033] In use, this invention involves attaching a photoelectric microneedle glucose monitoring sensor to the surface of the skin to be tested, allowing the microneedle array to penetrate the stratum corneum and contact the tissue fluid. A micro-light source is then activated to irradiate the enzyme-free photoelectric sensing layer. BiVO4 absorbs the light energy and generates electron-hole pairs. MXene extracts and transports the photogenerated electrons, and FeCoO4... x Capture photogenerated holes and promote glucose oxidation.

[0034] The signal acquisition module collects photocurrent changes in real time or intermittently, and then... Figure 4 The established standard curve is used to calculate the concentration or trend of glucose in tissue fluid. The standard curve can be established using photoelectric response curves at different glucose concentrations. In one application scenario, the sensor collects photoelectric response signals every 1-15 minutes and transmits the data to a mobile terminal or chronic disease management platform for displaying blood glucose trends, alerting to abnormal fluctuations, or for subsequent health management analysis.

[0035] like Figure 5 This study demonstrates the results of continuous glucose concentration monitoring using enzyme-free photoelectric microneedles, and compares them with reference blood glucose values ​​measured by a traditional blood glucose meter. In the experiment, a sugary beverage was consumed from a stable basal blood glucose level, resulting in a gradual increase in blood glucose levels, reaching a peak of approximately 9 mM after about 50 minutes, followed by a gradual decline. In the figure, the red curve represents the continuous monitoring results using the enzyme-free photoelectric microneedles, and the black dots represent the blood glucose meter measurements. Both methods showed good consistency in the glucose rise, peak appearance, and decline phases, indicating that the system can continuously track dynamic changes in glucose levels in vivo.

[0036] The photoelectric microneedle glucose monitoring sensor of this invention can be fabricated using processes such as hydrothermal synthesis, in-situ loading, molding, coating crosslinking, and flexible electrode integration. The process route is clear, facilitating adjustments to size, material ratios, and modular structure according to different wearing durations and detection requirements. This sensor can be used for glucose trend monitoring in tissue fluid of diabetic patients, blood glucose abnormality risk alerts, wearable devices for chronic disease management, and related in vitro or quasi-in vivo glucose detection scenarios, demonstrating promising industrial application prospects. Compared with existing technologies, the beneficial technical effects of this invention are: 1. Free from dependence on biological enzymes, with stability up to 21 days: This invention utilizes BiVO4-MXene-FeCoO4... x Ternary heterojunctions, as glucose photoelectrocatalytic sensing interfaces, avoid the problem of traditional enzyme-based sensors being deactivated by temperature, pH and storage environment. 2. High charge separation efficiency: MXene provides a fast electron transport channel, FeCoO x It promotes hole trapping and glucose oxidation, and the two work synergistically to reduce the recombination probability of photogenerated carriers in BiVO4 and improve the photoelectric response intensity; the results are as follows. Figure 4 BiVO4-MXene-FeCoO x The influence of composite materials on photoelectric response performance; and compared with pure bismuth vanadate, at an oxidation potential of 0.3V, BiVO4-MXene-FeCoO4... x The current response intensity of the ternary composite electrode is approximately 6-9 times that of pure BiVO4, indicating that the composite modification significantly enhances the photoelectrochemical activity of the electrode, and greatly improves the efficiency of charge separation and interfacial reaction. 3. Anti-interference capability: Adding a hydrogel anti-interference layer can weaken the influence of reducing substances and macromolecular components in tissue fluid and sweat, improving the detection stability under complex biological matrices; verification shows that glucose permeability can reach 98%, while other substances such as ascorbic acid and sweat are rejected by only 2%; 4. Minimally invasive and less painful: The microneedle array mainly penetrates the stratum corneum of the skin and comes into contact with tissue fluid, without touching the pain nerves in the dermis. Compared with traditional finger-prick blood sampling or deeper subcutaneous probes, it can reduce pain and foreign body sensation, and improve long-term monitoring compliance. 5. Easy to prepare on a large scale: This invention can be integrated using processes such as in-situ loading, microneedle molding and hydrogel coating, reducing complex biological enzyme immobilization and post-processing steps, which is beneficial for batch preparation.

Claims

1. A photoelectric microneedle glucose monitoring sensor, characterized in that, The system includes a flexible substrate 3, a conductive electrode layer 4 supported on the flexible substrate 3, a microneedle array 1 connected to the conductive electrode layer 4 and used for contacting subcutaneous tissue fluid, an enzyme-free photoelectric sensing layer 1-2 loaded on the surface of the microneedle array 1, a hydrogel anti-interference layer 2 covering the microneedle array 1, and a connecting micro-light source / photoelectric signal acquisition module 5 connected to the conductive electrode layer 4; wherein, the enzyme-free photoelectric sensing layer 1-2 includes BiVO4, MXene two-dimensional conductive material and FeCoO4. x The BiVO4, MXene and FeCoO x Together, they form a ternary heterojunction for enzyme-free photoelectrocatalytic oxidation detection of glucose, where x = 2~4, and Fe and Co are mainly Fe. 3+ and Co 3+ It also contains Fe-O-Co bonds.

2. The photoelectric microneedle glucose monitoring sensor according to claim 1, characterized in that, The BiVO4 is monoclinic scheelite phase BiVO4 nanoparticles; the MXene is Ti3C2T x T x This indicates variable end groups on the Ti3C2 surface, mainly including one or more of -O, -OH, and -F; the FeCoO x This is a simplified expression for Fe-Co oxide / hydroxy oxide composite cocatalyst.

3. The photoelectric microneedle glucose monitoring sensor according to claim 1, characterized in that, In the enzyme-free photosensitive layer, the mass percentage of MXene relative to BiVO4 is 10%-25%, and FeCoO4 is... x The loading relative to the BiVO4-MXene complex is 1%-10%.

4. The photoelectric microneedle glucose monitoring sensor according to claim 1, characterized in that, The microneedle array comprises multiple evenly distributed microneedles, all of which are hollow or coated microneedles, with a height of 200-1200 μm, a tip curvature radius of less than 50 μm, and a center-to-center distance of 300-1500 μm between adjacent microneedles. The microneedles are composed of an outer anti-interference hydrogel 2-1, an inner anti-interference hydrogel 2-2, a microneedle substrate 1-1, and an enzyme-free photoelectric sensing layer 1-2. The microneedle substrate 1-1 is made of a biocompatible polymer material, which is selected from one or a mixture of multiple materials in any mass ratio from chitosan, carboxymethyl chitosan, hyaluronic acid, sodium alginate, gelatin, gelatin methacrylamide, polyvinyl alcohol, polyvinylpyrrolidone, polyethylene glycol polymers, and 2-methacryloyloxyethyl phosphocholine polymers.

5. The photoelectric microneedle glucose monitoring sensor according to claim 1, characterized in that, The hydrogel anti-interference layer 2 is formed of an anti-sewage gel material, which is selected from one or more of chitosan, carboxymethyl chitosan, hyaluronic acid, sodium alginate, gelatin, polyvinyl alcohol, polyethylene glycol polymers, polyvinylpyrrolidone, 2-methacryloyloxyethyl phosphocholine polymers, sulfobetaine polymers, and carboxybetaine polymers. The hydrogel anti-interference layer is used to reduce the influence of proteins, uric acid, ascorbic acid, lactic acid, sweat components, or other reducing substances on the glucose detection signal. The conductive electrode layer 4 includes one or a mixture of multiple materials in any mass ratio selected from gold, platinum, silver / silver chloride, carbon materials, graphene, MXene, or conductive polymers.

6. The photoelectric microneedle glucose monitoring sensor according to claim 1, characterized in that, The photoelectric signal acquisition module 5 includes a miniature light source, a current acquisition unit, a data processing unit, and a wireless transmission unit; the emission wavelength of the miniature light source is 365-550 nm.

7. The method for preparing the photoelectric microneedle glucose monitoring sensor according to any one of claims 1-6, characterized in that, The process includes the following steps: 1) Preparing BiVO4 photocatalyst materials using hydrothermal synthesis or electrodeposition methods; 2) MXene two-dimensional conductive material was prepared by etching with hydrofluoric acid and lithium fluoride, and then combined with BiVO4 to form BiVO4-MXene composite material; 3) FeCoO2 was loaded onto the surface of BiVO4-MXene composite material by spin coating via dip-coating, electrodeposition, and photodeposition. x BiVO4-MXene-FeCoO x Ternary heterojunction materials; 4) A hydrogel anti-interference layer is formed inside the microneedle array and integrated with the conductive electrode layer, flexible substrate and photoelectric signal acquisition module; 5) The ternary heterojunction material, microneedle matrix material, conductive components and gel are filled into a microneedle mold, and after curing, drying and cross-linking, the mold is demolded to obtain the photoelectric microneedle glucose monitoring sensor.

8. The application of the photoelectric microneedle glucose monitoring sensor according to any one of claims 1-7 in tissue fluid glucose detection and blood glucose trend monitoring.

9. The application of the photoelectric microneedle glucose monitoring sensor according to any one of claims 1-7 in the warning of abnormal blood glucose risk.

10. The application of the photoelectric microneedle glucose monitoring sensor according to any one of claims 1-7 in chronic disease management devices or wearable health monitoring devices.

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