Photoelectrochemical sensing microneedles, their preparation methods, monitoring systems, and detection methods

Abstract

This application relates to the field of biomedical sensing and wearable health monitoring technology, and discloses a photoelectrochemical sensing microneedle and its preparation method, monitoring system, and detection method. The sensing microneedle comprises a swellable dual-network hydrogel microneedle matrix, a three-dimensional conductive network composed of high aspect ratio metal nanowires with localized surface plasmon resonance effect, and a semiconductor nanostructure composited on the surface of the metal nanowires to form a Schottky heterojunction. The mechanical constraint of the rigid polymer framework and the high aspect ratio of the metal nanowires synergistically ensure the continuity of the conductive network in the swelled state. Under excitation light irradiation, hot electrons migrate through the built-in electric field of the Schottky junction to the semiconductor surface to generate reactive oxygen free radicals. These free radicals then non-enzymatically catalyze the oxidation of target analytes in the interstitial fluid under zero or low bias voltage, generating a photocurrent signal, thus integrating minimally invasive sampling with in-situ highly selective detection.

Description

Technical Field

[0001] This application relates to the fields of biomedical sensing and wearable health monitoring technology, and in particular to sensing microneedles and their detection technology based on minimally invasive interstitial fluid sampling and in-situ photoelectrochemical recognition. Background Technology

[0002] Uric acid (UA) is the end product of purine metabolism in the human body and an important biomarker for assessing metabolic health. Abnormally elevated serum uric acid concentrations are closely related to gout, chronic kidney disease, diabetic complications, and cardiovascular disease. Therefore, real-time and accurate monitoring of uric acid levels has significant clinical value.

[0003] Currently, clinical uric acid testing mainly relies on venous blood sampling and large-scale biochemical analyzers. While these methods offer high accuracy, they are highly invasive, time-consuming, and cannot achieve high-frequency dynamic monitoring. Uric acid concentrations in non-invasive bodily fluids such as sweat and saliva are extremely low and fluctuate greatly due to physiological conditions and environmental factors, making it difficult to establish a reliable correlation with actual blood values. In contrast, uric acid concentrations in interstitial fluid (ISF) show a higher correlation with blood, making it a more clinically representative testing medium. Microneedle technology, as a minimally invasive sampling method, can obtain ISF by penetrating the superficial layers of the skin. However, existing rigid microneedles have poor biocompatibility and lack the ability to actively extract ISF, while ordinary hydrogel microneedles, although hydrophilic, lack sufficient mechanical strength. Balancing puncture force with fluid absorption characteristics remains a key challenge.

[0004] At the detection mechanism level, most existing portable uric acid sensors employ uricase catalysis. However, enzyme molecules are prone to denaturation and inactivation in the complex environment of the body, resulting in short sensor lifespan and the need for frequent calibration. Non-enzymatic electrochemical pathways typically require high bias voltages, while electroactive substances such as ascorbic acid (AA) and dopamine (DA) coexisting in interstitial fluid can cause severe co-oxidative interference at similar potentials. Furthermore, hydrogel microneedles are highly susceptible to signal distortion due to the breakage of their internal conductive network after absorbing liquid and swelling, posing another technical bottleneck to their long-term operation in body fluid environments. Summary of the Invention

[0005] This application provides a photoelectrochemical sensing microneedle and its preparation method, monitoring system and detection method. One of the technical problems it solves is: how to simultaneously achieve minimally invasive and efficient extraction of interstitial fluid and in-situ non-enzymatic photoelectrochemical highly selective detection of target analytes in a single microneedle structure, and maintain the continuity of electron transport in the internal conductive network under the hydrogel absorption and swelling state.

[0006] This application discloses a photoelectrochemical sensing microneedle, comprising:

[0007] A swellable dual-network hydrogel microneedle matrix comprising a rigid polymer backbone providing mechanical constraint and a hydrophilic polymer network providing fluid absorption capability, configured to undergo constrained volume swelling upon insertion into the skin and absorption of interstitial fluid;

[0008] A three-dimensional conductive network is in situ embedded inside the swellable dual-network hydrogel microneedle matrix. The three-dimensional conductive network is composed of interconnected metal nanowires with localized surface plasmon resonance effect and high aspect ratio.

[0009] A semiconductor nanostructure is composited on the surface of the metal nanowire and forms a Schottky heterojunction with the metal nanowire at the contact interface.

[0010] The mechanical constraint of the rigid polymer skeleton and the high aspect ratio of the metal nanowires are configured in a synergistic way to maintain the physical overlap between adjacent metal nanowires when the swellable dual-network hydrogel microneedle matrix undergoes volume swelling, so as to maintain the continuity of electron transport in the three-dimensional conductive network.

[0011] Under excitation light irradiation, the metal nanowires generate hot electrons based on the localized surface plasmon resonance effect. Driven by the built-in electric field of the Schottky heterojunction, the hot electrons migrate to the semiconductor nanostructure and generate reactive oxygen free radicals to perform non-enzymatic catalytic oxidation of the target analyte in the interstitial fluid inside the matrix at a bias voltage with an absolute value of less than 0.3V, and generate a photocurrent signal.

[0012] In a preferred embodiment, the swellable dual-network hydrogel microneedle matrix is ​​a physically cross-linked dual-network hydrogel composed of polyvinyl alcohol and polyvinylpyrrolidone, wherein the mass ratio of polyvinyl alcohol to polyvinylpyrrolidone is 100:(0.5~5).

[0013] The microcrystalline regions formed by the polymer chains of polyvinyl alcohol during the physical cross-linking process constitute the rigid polymer skeleton, which provides puncture force to penetrate the stratum corneum of the skin in a dry state and limits excessive expansion in a wet state.

[0014] The polyvinylpyrrolidone forms the hydrophilic polymer network and is dispersed in the gaps of the microcrystalline region, which is used to form an osmotic pressure difference with the interstitial fluid to drive the body fluid to diffuse into the microneedles.

[0015] In a preferred embodiment, the metal nanowire is a silver nanowire with a length of 30-150 μm; the semiconductor nanostructure is a titanium dioxide nanostructure, which is in the form of a nanorod and grows in situ radially outward from the silver nanowire as the axis, forming a sea urchin-like composite morphology with a large three-dimensional specific surface area.

[0016] In a preferred embodiment, the target analyte is uric acid, and the reactive oxygen species is superoxide radical;

[0017] The non-enzymatic catalytic oxidation specifically includes: the hot electrons that migrate directionally to the surface of the semiconductor nanostructure undergo a reduction reaction with dissolved oxygen molecules to generate superoxide radicals, and the superoxide radicals are used to specifically oxidize uric acid into allantoin under zero bias voltage, so as to avoid the co-oxidation interference of electroactive substances coexisting in the interstitial fluid from a thermodynamic perspective.

[0018] In a preferred embodiment, the height of a single microneedle in the microneedle matrix is ​​800~1500μm, and the width of the matrix is ​​300~600μm; the breaking force of a single microneedle in the microneedle matrix under dry conditions is greater than 0.4 N.

[0019] This application also discloses a wearable photoelectrochemical monitoring system, comprising:

[0020] Flexible patch substrate;

[0021] The microneedle sensing array is disposed on the flexible patch substrate and includes at least a working electrode microneedle and a counter electrode and a reference electrode that are insulated and isolated from it, wherein the working electrode microneedle is a photoelectrochemical sensing microneedle as described above.

[0022] A light source module, disposed on the flexible patch substrate, is configured to provide the excitation light to the interior of the microneedle sensing array; and

[0023] The signal acquisition and processing module is electrically connected to the microneedle sensing array and is configured to acquire the photocurrent signal output by the working electrode microneedle under a bias voltage with an absolute value of less than 0.3V, and convert the photocurrent signal into concentration data of the target analyte.

[0024] In a preferred embodiment, the light source module includes a miniature light-emitting diode array;

[0025] The signal acquisition and processing module is mounted on a flexible printed circuit board and includes a potentiostat circuit, a transimpedance amplifier, and a microcontroller unit with integrated low-power Bluetooth communication functionality.

[0026] The working electrode microneedle, the counter electrode, and the reference electrode are connected to the signal acquisition and processing module via conductive circuits screen-printed on the flexible patch substrate;

[0027] The system also includes a flexible protective layer covering the flexible printed circuit board.

[0028] This application also discloses a method for detecting target analytes based on minimally invasive interstitial fluid sampling and in-situ photoelectrochemical recognition, including the following steps:

[0029] An electrochemical sensing microneedle array is attached to the skin surface to allow it to penetrate the stratum corneum and reach the dermis in a minimally invasive manner. The electrochemical sensing microneedle array is made of a swellable dual-network hydrogel. Metal nanowires with localized surface plasmon resonance effect and high aspect ratio are in situ embedded in the swellable dual-network hydrogel to form a three-dimensional conductive network. Semiconductor nanostructures are composited on the surface of the metal nanowires and form Schottky heterojunctions with the metal nanowires.

[0030] The swelling effect of the swellable dual-network hydrogel allows subcutaneous interstitial fluid to be extracted into the photoelectrochemical sensing microneedle array. Under the mechanical constraint of the rigid polymer skeleton in the hydrogel and the synergistic effect of the high aspect ratio of the metal nanowires, the three-dimensional conductive network maintains the continuity of the electron transport channel through the flexible overlap between the wires.

[0031] The Schottky heterojunction is excited by a light source, and the metal nanowire generates hot electrons based on the plasma resonance effect. The hot electrons migrate to the surface of the semiconductor nanostructure under the drive of the built-in electric field of the Schottky heterojunction and react with dissolved oxygen to generate reactive oxygen free radicals.

[0032] The reactive oxygen free radicals perform in-situ specific non-enzymatic catalytic oxidation of the target analyte in the interstitial fluid under zero bias voltage or low bias voltage conditions, generating a photocurrent signal related to the concentration of the target analyte.

[0033] The photocurrent signal is collected and processed to obtain the concentration information of the target analyte.

[0034] This application also discloses a method for preparing the above-mentioned photoelectrochemical sensing microneedles, comprising the following steps:

[0035] Fabrication of high aspect ratio metal nanowires with localized surface plasmon resonance effect;

[0036] Semiconductor nanostructures were constructed on the surface of the metal nanowires by in-situ growth, forming a Schottky heterojunction composite material of metal nanowires and semiconductor nanostructures.

[0037] The composite material is dispersed in a prepolymer solution containing a rigid polymer backbone precursor and a hydrophilic polymer;

[0038] A prepolymer containing the composite material is filled into a microneedle mold and then formed into a microneedle array with a swellable dual-network hydrogel microneedle matrix through a crosslinking process.

[0039] In a preferred embodiment, the metal nanowires are silver nanowires, prepared by a polyol method using polyvinylpyrrolidone and silver nitrate reacting in an ethylene glycol medium and introducing a halide salt as a crystal form inducing agent.

[0040] The in-situ growth method is a hydrothermal method, in which the silver nanowires are dispersed in a hydrothermal reaction solution containing a titanium source precursor and reacted at 180~220℃, so that the titanium dioxide nanostructure grows in a directional manner with the silver nanowires as a template to form a sea urchin-like composite morphology.

[0041] In the embodiments of this application, a three-dimensional conductive network is constructed by in-situ embedding high-aspect-ratio metal nanowires with localized surface plasmon resonance effect within a swellable dual-network hydrogel microneedle matrix. A semiconductor nanostructure is then composited on the surface of the metal nanowires to form a Schottky heterojunction. Simultaneously, the mechanical constraint of the rigid polymer framework and the high aspect ratio of the metal nanowires synergistically maintain the continuity of electron transport in the conductive network under swellable conditions. This allows for the simultaneous, minimally invasive, and efficient extraction of subcutaneous interstitial fluid and in-situ photoelectrochemical detection of target analytes within a single microneedle structure, eliminating signal attenuation and technical losses caused by the spatial separation of body fluid extraction and detection in traditional microneedle methods. Furthermore, the built-in electric field of the Schottky heterojunction drives thermal... Electron migration and the generation of reactive oxygen species enable non-enzymatic catalytic oxidation of target analytes at zero or low bias voltages. This thermodynamically avoids co-oxidation interference from coexisting electroactive substances such as ascorbic acid and dopamine in interstitial fluid, significantly improving molecular selectivity and signal-to-noise ratio. Simultaneously, it eliminates dependence on biological enzymes, overcoming the shortcomings of enzyme sensors such as short lifespan and frequent calibration due to inactivation caused by changes in temperature, humidity, and pH. This endows the sensing microneedle with the ability to operate stably for extended periods in complex bodily fluid environments. Furthermore, the anti-swelling conductive network design ensures that the hydrogel maintains reliable electrochemical response consistency even after absorbing interstitial fluid and undergoing volume swelling, providing a structural basis for continuous dynamic monitoring in wearable applications.

[0042] Furthermore, by using polyvinyl alcohol and polyvinylpyrrolidone in a specific mass ratio to form a physically cross-linked double-network hydrogel, the polyvinyl alcohol microcrystalline region is used as a rigid skeleton to provide puncture force in the dry state and limit excessive expansion in the wet state. At the same time, the hydrophilic properties of polyvinylpyrrolidone are used to form an osmotic pressure difference with the interstitial fluid to drive the diffusion of body fluid. This can balance the mechanical puncture strength of the microneedle with the rapid body fluid absorption capacity, and solve the performance contradiction between the puncture hardness and swelling sampling rate of the flexible microneedle material.

[0043] Furthermore, by using silver nanowires with a length of 30~150μm as metal nanowires and growing nanorod-shaped titanium dioxide in situ with the silver nanowires as the axis to form a sea urchin-like three-dimensional composite morphology with a large specific surface area, the photoactive interface area can be increased to improve light capture efficiency and photoelectric conversion efficiency. At the same time, the high aspect ratio of silver nanowires is beneficial to maintaining a stable conductive overlap network after the hydrogel swells.

[0044] Furthermore, by utilizing superoxide radicals to specifically oxidize uric acid to allantoin under zero bias voltage, the co-oxidation interference of coexisting electroactive substances such as ascorbic acid, dopamine, and glucose in the interstitial fluid at high potentials can be avoided from a thermodynamic perspective, thereby achieving highly selective and accurate detection of uric acid molecules.

[0045] Furthermore, by limiting the height of a single microneedle to 800~1500μm, the base width to 300~600μm, and the breaking force to greater than 0.4N in a dry state, it can be ensured that the microneedle has sufficient mechanical strength to penetrate the human stratum corneum without bending or breaking, while controlling the puncture depth within the dermis to achieve minimally invasive and painless sampling.

[0046] By integrating a microneedle sensing array containing working electrode microneedles, counter electrode and reference electrode on a flexible patch substrate, and in conjunction with a light source module and a signal acquisition and processing module, a complete closed-loop process from interstitial fluid sampling, photoelectrochemical excitation detection to signal processing output can be realized on a single wearable patch. This transforms the traditional photoelectrochemical detection that relies on large laboratory equipment into a portable monitoring platform that can operate in real time on the skin surface.

[0047] Furthermore, by using a micro LED array as the light source, a potentiostat circuit, a transimpedance amplifier, and a microcontroller unit with low-power Bluetooth communication function are integrated on a flexible printed circuit board. The electrical connection between each electrode and the signal module is achieved through screen-printed conductive circuits. This enables the system to be ultra-lightweight and highly integrated, meeting the requirements for portability, low power consumption, and wireless data transmission in home continuous monitoring scenarios.

[0048] Furthermore, by using a polyol method to prepare silver nanowires with halide salts as crystal inducing agents, and by using a hydrothermal method to directionally grow titanium dioxide with silver nanowires as templates at 180~220℃ to form a sea urchin-like composite morphology, it is possible to achieve close in-situ composite of semiconductor nanostructures on the surface of metal nanowires, construct a Schottky heterojunction with a stable metal-semiconductor contact interface, and ensure the effective establishment of the built-in electric field at the interface and the efficient separation and directional migration of photogenerated carriers. Attached Figure Description

[0049] Figure 1This is a schematic diagram of the structure of the photoelectrochemical sensing microneedle described in Embodiment 1 of this application;

[0050] Figure 2 This is a schematic diagram of the overall structure of the wearable photoelectrochemical monitoring system described in Embodiment 3 of this application;

[0051] Figure 3 This is a timing flowchart of the detection method described in Embodiment 4 of this application;

[0052] Figure 4 This is a photograph of the microneedle patch used in Embodiment 5 of this application on living skin for verification.

[0053] Figure 5 This is a flowchart illustrating the preparation process of the anti-expansion conductive photoelectrochemical hydrogel microneedles described in Embodiment 2 of this application.

[0054] Figure 6 This is a schematic diagram of the photocathode uric acid detection mechanism in Embodiment 1 of this application. Detailed Implementation

[0055] To make the objectives, technical solutions, and advantages of this application clearer, the application will be further described in detail below with reference to the accompanying drawings and specific embodiments. It should be understood that the following embodiments are only used to illustrate the technical solutions of this application and should not be considered as limiting the scope of protection of this application. Where there is no conflict, the following embodiments and their technical features can be combined with each other.

[0056] Example 1

[0057] This embodiment provides a photoelectrochemical sensing microneedle that can minimally penetrate the stratum corneum of the skin and extract subcutaneous interstitial fluid in situ. Simultaneously, under zero or low bias voltage conditions, it performs non-enzymatic catalytic oxidation detection of target analytes in the interstitial fluid via a photoelectrochemical mechanism. The overall structure of this sensing microneedle and its components are described in detail below.

[0058] Reference Figure 1 The photoelectrochemical sensing microneedle in this embodiment mainly includes a swellable dual-network hydrogel microneedle substrate 10, a three-dimensional conductive network 20 embedded in situ within the substrate, and a semiconductor nanostructure 30 composited on the surface of metal nanowires within the conductive network. These three components are highly coupled structurally and synergistically cooperate functionally, enabling a single microneedle structure to simultaneously perform the dual tasks of body fluid sampling and photoelectrochemical detection.

[0059] I. Swellable dual-network hydrogel microneedle matrix

[0060] The swellable dual-network hydrogel microneedle matrix serves as the structural carrier for the entire sensing microneedle. Its core function is to provide sufficient mechanical strength to penetrate the stratum corneum 101 and reach the dermis 102 (without needing to reach the subcutaneous tissue 103), and to actively absorb subcutaneous interstitial fluid through constrained volume swelling after insertion into the skin. This matrix consists of two functionally complementary polymer networks: a rigid polymer framework that provides mechanical constraint, and a hydrophilic polymer network that provides the ability to absorb body fluids.

[0061] A rigid polymer framework plays a key structural support role in the microneedle matrix. This framework consists of ordered microcrystalline regions formed by physical cross-linking of polymer chains (e.g., hydrogen bonding or microcrystalline cross-linking). These microcrystalline regions impart sufficient rigidity and compression resistance to the microneedles in their dry state, enabling them to withstand the puncture force required to penetrate the stratum corneum without bending or breaking. Simultaneously, these microcrystalline regions provide spatial constraint during the water absorption and swelling process of the microneedles, limiting excessive expansion of the hydrogel network and allowing the microneedles to maintain their basic geometric shape and structural integrity after absorbing interstitial fluid.

[0062] A hydrophilic polymer network is dispersed within the intercellular spaces of the microcrystalline region formed by the rigid polymer backbone, serving as the driving force for fluid adsorption. Due to its high intrinsic hydrophilicity, this hydrophilic polymer network can create a significant osmotic pressure difference with the subcutaneous interstitial fluid, thereby driving water molecules and solutes (including target analyte molecules) in the interstitial fluid into the microneedle matrix via passive diffusion. When the microneedle array is inserted into the skin, the hydrophilic polymer network rapidly absorbs water and swells. The interstitial fluid diffuses along the porous network structure of the hydrogel into the microneedles under the combined action of capillary force and osmotic pressure, thus achieving efficient fluid transport from the subcutaneous tissue to the microneedle sensing interface.

[0063] The synergistic effect of the aforementioned dual-network structure enables the microneedle matrix to exhibit a "constrained volume swelling" characteristic: on the one hand, the hydrophilic polymer network provides a strong water absorption driving force, ensuring that the interstitial fluid can be fully extracted into the microneedle in a short time; on the other hand, the rigid polymer framework limits the degree and rate of swelling through the mechanical constraint of its microcrystalline regions, preventing the microneedle from losing its structural integrity or detaching from the skin interface due to excessive expansion. In this embodiment, the microneedle matrix can reach a swelling rate of approximately 125% within about 60 seconds after being inserted into the skin. This swelling rate and degree meet the requirements of rapid sampling without compromising the geometric structure and continuity of the internal conductive network of the microneedle due to excessive expansion.

[0064] It should be noted that the aforementioned rigid polymer backbone can be selected from various polymeric materials capable of forming physically cross-linked microcrystalline regions, such as polyvinyl alcohol (PVA), chitosan, or modified cellulose; the hydrophilic polymer network can be selected from polymers with high hydrophilicity, such as polyvinylpyrrolidone (PVP), polyacrylic acid (PAA), and polyethylene glycol (PEG). Those skilled in the art can flexibly select the specific material combination of the rigid polymer backbone and the hydrophilic polymer network according to the required mechanical strength, swelling rate, and biocompatibility requirements.

[0065] Two-dimensional and three-dimensional conductive networks

[0066] A three-dimensional conductive network is in situ embedded within a swellable dual-network hydrogel microneedle matrix. Its function is to provide an electron transport channel for photoelectrochemical reactions and simultaneously participate in the photoenergy conversion process as a plasmon resonance center. This three-dimensional conductive network is composed of interconnected metal nanowires with a high aspect ratio exhibiting localized surface plasmon resonance (LSPR) effect.

[0067] The metal nanowires are selected from noble metal or alloy nanowires exhibiting significant LSPR effects, such as silver nanowires (AgNWs), gold nanowires (AuNWs), or copper nanowires (CuNWs). The metal nanowires possess a high aspect ratio, with their length significantly exceeding the deformation scale of the microneedle matrix before and after swelling. In the prepolymerization stage, the metal nanowires are uniformly dispersed in the hydrogel precursor; after cross-linking, the nanowires form a random but highly interconnected three-dimensional overlapping network within the microneedle matrix. Due to the high conductivity of the metal nanowires, this overlapping network provides a low-impedance continuous pathway for electron collection and transport in the electrochemical reaction, enabling the photoelectrochemical detection signal generated in situ within the microneedle to be efficiently transmitted to the external acquisition circuit.

[0068] The LSPR effect of metal nanowires is another core functional feature of this conductive network. When excitation light shines on the surface of the metal nanowires, the free electrons in the nanowires undergo collective oscillations under the action of the incident photoelectric field, forming localized surface plasmon resonance. This resonance effect significantly enhances the local electromagnetic field intensity on the surface of the metal nanowires and can convert the captured light energy into high-energy hot electrons, providing energy input for subsequent photoelectric conversion at the Schottky heterojunction interface.

[0069] III. Semiconductor Nanostructures and Schottky Heterojunctions

[0070] Semiconductor nanostructures are composited on the surface of metal nanowires, forming a Schottky heterojunction at the interface. These semiconductor nanostructures can be selected from n-type semiconductor materials with suitable band gaps, such as titanium dioxide (TiO2), zinc oxide (ZnO), and cadmium sulfide (CdS). Using the metal nanowires as templates or axes, the semiconductor nanostructures are grown in situ to form a tight heterojunction on their surface. Due to the difference in work function between the metal and the n-type semiconductor, a space charge region and a built-in electric field, i.e., a Schottky barrier, are spontaneously formed at the interface. This built-in electric field is directed from the semiconductor to the metal (for n-type semiconductors), driving photogenerated electrons to migrate directionally from the metal side to the semiconductor side.

[0071] The morphology design of semiconductor nanostructures has a significant impact on photoelectrochemical performance. In this embodiment, the semiconductor nanostructures are arranged in high specific surface area morphologies such as nanorods, nanosheets, or nanospikes to increase the contact area with dissolved oxygen and target analyte molecules in the interstitial fluid, thereby improving the efficiency of the catalytic reaction. When the semiconductor nanostructures are arranged in a nanorod shape and radially outward from the axis of metal nanowires, a three-dimensional composite morphology resembling an urchin is formed. This structure significantly increases the light-harvesting area and the number of catalytically active sites.

[0072] IV. Anti-expansion synergistic mechanism

[0073] One of the key technical features of this embodiment is the synergistic configuration between the mechanical constraint of the rigid polymer skeleton and the high aspect ratio of the metal nanowires. This synergistic configuration ensures that when the swellable double-network hydrogel microneedle matrix undergoes volume swelling, the adjacent metal nanowires can still maintain physical overlap, thereby maintaining the continuity of electron transport in the three-dimensional conductive network.

[0074] Specifically, when the microneedle matrix absorbs water and swells, the hydrogel network undergoes isotropic or near-isotropic volume expansion. If the metal nanowires are short, during the hydrogel expansion process, the overlap points between adjacent nanowires may detach due to the increased spacing between the wires, leading to a break in the conductive path, a sharp increase in resistance, and consequently, attenuation or even loss of the photocurrent signal. This embodiment solves this problem through a two-pronged design. On the one hand, the microcrystalline regions provided by the rigid polymer framework act as spatial constraint nodes, limiting the maximum swelling degree of the hydrogel network and controlling the volume expansion of the microneedle matrix within a certain range. On the other hand, the high aspect ratio of the metal nanowires ensures that the length of a single nanowire is much greater than the change in spacing caused by swelling. During the microneedle swelling process, the high aspect ratio nanowires can adapt to the deformation of the matrix through flexible bending and sliding between the wires. At the same time, since there are multiple overlap points between a single nanowire and multiple adjacent nanowires, even if some overlap points detach during the swelling process, the entire three-dimensional network can still maintain macroscopic conductivity through redundant overlap paths.

[0075] Taking this embodiment as an example, when the microneedle matrix undergoes a 125% swelling rate, the resistance change rate of the internal three-dimensional conductive network is controlled within an acceptable range, and the deviation of the photocurrent signal does not exceed 5%. This "swelling-tolerant" design ensures that the sensing microneedles can work stably and sustainably in complex bodily fluid environments.

[0076] V. Photoelectric Detection Mechanism

[0077] Reference Figure 6 The detection process of the photoelectrochemical sensing microneedle under excitation light irradiation in this embodiment is as follows. Figure 6 This is a schematic diagram of the photocathode uric acid detection mechanism. The left side represents silver nanowires (labeled "silver nanowires" in the figure), and the elliptical area in the middle represents the energy band structure of titanium dioxide nanostructures grown in situ with silver nanowires as the axis. Figure 6 In titanium dioxide semiconductors, the "conduction band" (CB) refers to the lowest empty energy band that electrons can occupy, that is, the energy range in which electrons can move freely after being excited; the "valence band" (VB) refers to the highest energy band that electrons fill in the ground state in titanium dioxide semiconductors. Figure 6 The -0.37 eV indicated in the figure represents the potential of the conduction band bottom of titanium dioxide as -0.37 eV (relative to the standard hydrogen electrode NHE), and the 2.57 eV represents the potential of the valence band top of titanium dioxide as 2.57 eV (relative to the standard hydrogen electrode NHE). The difference between the two is the band gap of titanium dioxide (approximately 2.94 eV). Figure 6 The "e" -The arrow indicates the process by which hot electrons migrate from one side of the silver nanowire to the titanium dioxide conduction band under the drive of the built-in electric field of the Schottky heterojunction.

[0078] When excitation light emitted from an external light source is incident on the microneedle substrate, the metal nanowires embedded in the substrate absorb the light energy and generate high-energy hot electrons based on localized surface plasmon resonance. These hot electrons gain energy exceeding the height of the Schottky barrier and, driven by the built-in electric field of the Schottky heterostructure, migrate unidirectionally from one side of the metal nanowire to the conduction band of the semiconductor nanostructure. The electrons migrating to the conduction band of the semiconductor nanostructure are at a potential of -0.37 eV (vs NHE), while dissolved oxygen molecules are reduced to superoxide radicals (…). The standard reduction potential of titanium dioxide is -0.33 V (vs NHE). Since the conduction band bottom potential of titanium dioxide (-0.37 eV) is more negative than the reduction potential of oxygen molecules / superoxide radicals (-0.33 V), meaning the reducing power of the conduction band electrons is sufficient to reduce dissolved oxygen molecules to superoxide radicals, the two satisfy the reduction potential matching condition—this is... Figure 6 The meaning of "reduction potential matching" shown is that the potential of the semiconductor conduction band electrons must be more negative than the standard potential of the target reduction reaction in order to thermodynamically drive the spontaneous reduction reaction. Therefore, the hot electrons migrating to the titanium dioxide conduction band can react with dissolved oxygen molecules in the interstitial fluid to generate highly chemically reactive superoxide radicals (SVO2+). This reactive oxygen species can also be a hydroxyl radical ( ). Other strong oxidizing species, such as , depend on the band position of the selected semiconductor material and the reaction conditions.

[0079] When target analyte molecules in the subcutaneous interstitial fluid diffuse to the surface of the semiconductor nanostructure through a hydrogel network, a specific non-enzymatic catalytic oxidation reaction occurs between the aforementioned reactive oxygen species and the target analyte molecules. This oxidation reaction consumes electrons and is accompanied by a change in photocathode current, the magnitude of which is quantitatively related to the concentration of the target analyte. Since the above photoelectrochemical reaction process is driven by the hot electrons generated by the LSPR effect and the built-in electric field of the Schottky junction, the system can operate efficiently under zero bias voltage (0V) or low bias voltage (e.g., absolute value below 0.3V) conditions without the need for an additional high oxidation potential. This characteristic thermodynamically avoids co-oxidation interference from other coexisting electroactive substances in the interstitial fluid at high potentials, significantly improving the selectivity and signal-to-noise ratio of the detection.

[0080] In summary, the photoelectrochemical sensing microneedle of this embodiment achieves minimally invasive puncture and body fluid extraction through a swellable dual-network hydrogel microneedle matrix. It constructs an anti-expansion three-dimensional conductive network using internally embedded high aspect ratio metal nanowires, and forms a Schottky heterojunction through in-situ grown semiconductor nanostructures on the surface of the metal nanowires. Hot electrons generated by LSPR migrate to the semiconductor surface under the drive of a built-in electric field, generating reactive oxygen species (ROS). This enables highly selective non-enzymatic photoelectrocatalytic oxidation detection of target analytes in interstitial fluid at zero or low bias voltages. This microneedle spatially integrates "sampling" and "detection" functions, simplifying the path from body fluid extraction to signal generation and significantly reducing signal attenuation.

[0081] The following describes several optional improvements to the sensing microneedles in this embodiment.

[0082] In some alternative implementations, the swellable dual-network hydrogel microneedle matrix can be prepared from a physically cross-linked dual-network hydrogel composed of polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP), wherein the mass ratio of PVA to PVP is 100:(0.5~5). Within this ratio range, the microcrystalline regions formed by the PVA polymer chains during the physical cross-linking process (e.g., room temperature drying hydrogen bonding cross-linking or freeze-thaw cycle cross-linking) constitute a rigid polymer backbone, providing puncture force to penetrate the stratum corneum in the dry state and limiting excessive swelling in the wet state. PVP constitutes a hydrophilic polymer network and is dispersed in the intercellular spaces of the microcrystalline regions. Its high hydrophilicity allows it to form a significant osmotic pressure difference with the interstitial fluid, thereby driving the body fluid to diffuse rapidly into the microneedle.

[0083] The mass ratio of PVA to PVP determines the relative proportion between the rigid framework and the hydrophilic network, thus affecting the puncture strength and swelling sampling rate of the microneedles. When the relative content of PVP is low (e.g., a mass ratio of 100:0.5 in one embodiment), the PVA microcrystalline region dominates in the matrix, resulting in high dry stiffness and puncture strength of the microneedles, but the hydrophilic network is relatively sparse, leading to a relatively slow swelling rate and interstitial fluid extraction rate. When the relative content of PVP is high (e.g., a mass ratio of 100:5 in one embodiment), the hydrophilic network is more abundant, the swelling driving force is enhanced, and the interstitial fluid sampling rate is significantly accelerated, but the relative volume proportion of the PVA microcrystalline region decreases, and the puncture strength decreases accordingly. Within the entire ratio range of 100:(0.5~5), the PVA microcrystalline region can form an effective rigid framework, ensuring that the fracture force of the microneedles in the dry state meets the mechanical requirements for penetrating the stratum corneum. At the same time, the PVP hydrophilic network can establish a sufficient osmotic pressure difference with the interstitial fluid to drive the diffusion of body fluids. In a preferred formulation, the mass ratio of PVA to PVP is 100:1.25. This ratio achieves a good balance between puncture strength and swelling absorption rate, with the microneedles reaching a swelling rate of approximately 125% within about 60 seconds and a single microneedle breaking force of approximately 0.48 N. When the PVA / PVP system is not used, other polymer combinations capable of forming a dual-network structure can also be selected, such as the PVA / polyacrylic acid (PAA) system or the chitosan / PEG system. Those skilled in the art can flexibly adjust the formulation according to actual mechanical properties and biocompatibility requirements.

[0084] As a preferred but not essential improvement, the aforementioned metal nanowires can be silver nanowires (AgNWs) with a length of 30~150μm. Silver nanowires have a strong LSPR effect in the visible light range and extremely high conductivity.

[0085] The length of silver nanowires directly affects the anti-swelling performance and photoelectrochemical response characteristics of three-dimensional conductive networks. When the length of the silver nanowires is short (e.g., approximately 30 μm in one embodiment), the spatial span of a single nanowire in the hydrogel matrix is ​​small, resulting in better dispersion uniformity in the prepolymer solution and a more uniform spatial distribution of the conductive network after molding. However, due to the relatively small number of overlap points between a single nanowire and adjacent nanowires, the redundancy in maintaining the continuity of the conductive pathway during hydrogel swelling is relatively low, and the tolerance margin for the degree of swelling is small. When the length of the silver nanowires is long (e.g., approximately 150 μm in one embodiment), a single nanowire spans a larger spatial range, forming more overlap points with adjacent nanowires. Even when the spacing between lines increases due to hydrogel swelling, the continuity of the conductive network can still be maintained through sufficient redundant overlap paths, resulting in stronger anti-swelling stability of the three-dimensional conductive network. However, excessively long nanowires are more difficult to disperse in the prepolymer solution, and are prone to entanglement and local aggregation, which may lead to uneven network distribution. Within a length range of 30–150 μm, the lengths of the silver nanowires are significantly greater than the deformation scale of the microneedle matrix during swelling. This allows them to adapt to the volume expansion of the matrix through flexible bending and sliding between the nanowires, maintaining the continuity of electron transport in the three-dimensional conductive network, while remaining mechanically constrained by the rigid polymer framework. Simultaneously, the silver nanowires within this length range possess sufficient aspect ratio to exhibit a significant localized surface plasmon resonance (LSPR) effect, enabling efficient generation of hot electrons under excitation light irradiation. In a preferred embodiment, the silver nanowires have a length of approximately 80 μm and a diameter of approximately 60–100 nm, achieving a good overall balance between dispersion uniformity, overlap redundancy, and the intensity of the LSPR effect.

[0086] Semiconductor nanostructures can utilize titanium dioxide (TiO2) nanostructures. These TiO2 nanostructures are rod-shaped and radiate outwards from silver nanowires in situ, forming a three-dimensional, urchin-like composite morphology with a large specific surface area, namely the AgNWs@ULTiO2 structure. This urchin-like morphology allows each silver nanowire to be loaded with a large number of TiO2 nanorods, significantly increasing the Schottky heterojunction interface area and the number of catalytically active sites, which is beneficial for improving visible light utilization and the generation efficiency of reactive oxygen species. Besides silver nanowires, gold or copper nanowires can also be used; and in addition to TiO2, other materials with suitable band structures, such as ZnO nanorods or CdS nanoparticles, can also be used for semiconductor nanostructures.

[0087] Optionally, the target analyte can specifically be uric acid (UA), and correspondingly, the reactive oxygen species can be superoxide radicals (SOR). In this specific application scenario, the photoelectrochemical non-enzymatic catalytic oxidation process is as follows: hot electrons that migrate directionally to the surface of the semiconductor nanostructure react with oxygen molecules dissolved in the interstitial fluid. A reduction reaction occurs, generating superoxide radicals ( ). Subsequently, superoxide radicals specifically oxidize uric acid molecules diffused from the interstitial fluid to the semiconductor surface into allantoin under zero bias voltage. This oxidation reaction is accompanied by an increase in photocathode current, with the increase in current being proportional to the uric acid concentration. Since the above reaction can proceed efficiently at 0V bias, and the oxidation potentials of common coexisting electroactive substances in the interstitial fluid, such as ascorbic acid (AA), dopamine (DA), and glucose, are significantly higher than 0V, these interfering substances will not undergo electrochemical oxidation reactions in this detection system, achieving highly selective recognition of uric acid molecules from a thermodynamic perspective. It should be noted that uric acid is only one preferred target analyte in this application. By adjusting the band structure of the semiconductor material or changing the catalytic system, this detection method is also applicable to the detection of other electroactive small molecules, such as dopamine, creatinine, or amino acid metabolites.

[0088] To further improve the puncture reliability and wearing safety of microneedles, the height of a single microneedle in the microneedle matrix can be set in the range of 800~1500μm, and the base width can be set in the range of 300~600μm.

[0089] The height and base width of the microneedle directly affect the puncture depth, mechanical strength, and wearing safety. When the microneedle height is low (e.g., approximately 800 μm in one embodiment), the depth of penetration into the dermis after penetrating the stratum corneum is shallow, minimizing the probability of touching nerve endings and capillaries, resulting in minimal pain and bleeding risk during the puncture process and maximizing wearing safety. Simultaneously, due to the smaller overall height of the microneedle, the cone angle is relatively larger for the same base width, resulting in a more robust overall structure and stronger bending resistance. However, a shallower puncture depth means a relatively smaller contact area between the microneedle and the interstitial fluid in the dermis, potentially leading to a lower extraction volume. When the microneedle height is high (e.g., approximately 1500 μm in one embodiment), the microneedle can penetrate the stratum corneum and epidermis to reach deeper into the dermis, resulting in a larger contact area with the interstitial fluid, which is beneficial for improving the extraction rate and volume of the interstitial fluid. However, the puncture depth should not exceed the upper dermis to avoid touching deep dermal nerve endings and capillary networks. Regarding the base width, a smaller base width (e.g., approximately 300 μm in one embodiment) makes the microneedle tip sharper, requiring less pressure to penetrate the stratum corneum, but the cross-sectional compressive strength is relatively lower; a larger base width (e.g., approximately 600 μm in one embodiment) provides a larger cross-sectional area, resulting in greater overall stiffness and flexural strength of the microneedle, but correspondingly increased puncture resistance. Within a height range of 800–1500 μm and a base width range of 300–600 μm, the mechanical properties of the PVA / PVP dual-network hydrogel material ensure that the breaking force of the microneedle in a dry state is greater than 0.4 N. This force value far exceeds the minimum force required to penetrate the human stratum corneum (generally 0.05–0.1 N / needle), ensuring that the microneedle will not bend or break during pressure application; at the same time, the puncture depth is controlled within the dermis layer, without touching subcutaneous tissue, meeting the safety requirements of minimally invasive and painless sampling.

[0090] In a preferred size configuration, the height of a single microneedle is 1200 μm, the base width is 500 μm, and the microneedle is pyramidal in shape. This size design achieves an optimal balance between puncture depth, interstitial fluid contact area, mechanical strength, and wearing comfort, with a single microneedle breaking force of approximately 0.48 N in a dry state. Of course, those skilled in the art can adjust the microneedle size within the above range according to the specific monitoring site (e.g., forearm, abdomen) and skin characteristics (e.g., elderly skin, children's skin).

[0091] Example 2

[0092] This embodiment provides a method for preparing photoelectrochemical sensing microneedles according to Example 1, such as... Figure 5As shown, the preparation method mainly includes four steps: metal nanowire preparation, in-situ growth of semiconductor nanostructures, prepolymer solution preparation, and microneedle forming. Each step is described in detail below.

[0093] Step 501: Prepare high aspect ratio metal nanowires with localized surface plasmon resonance (LSPR) effect. In this embodiment, silver nanowires are used as an example, but this step is also applicable to the preparation of other metal nanowires with LSPR effect. Specifically, an appropriate amount of polymeric surfactant is dissolved in a polyol solvent, heated to a predetermined temperature, and then a silver salt precursor solution is added. A trace amount of halide salt or metal chloride is introduced as a crystal form inducing agent to promote the crystallization of silver nanowires. <110> Anisotropic growth was observed. The reaction was carried out under stirring for several hours until the solution showed a silvery-gray filamentous suspension, indicating that a large amount of high aspect ratio silver nanowires had been generated. After the reaction, unreacted precursors and byproducts were removed by centrifugation and repeated solvent washing, finally obtaining a high-purity silver nanowire suspension dispersed in an alcohol solvent. The length of the obtained silver nanowires can be controlled by reaction time, reaction temperature, and the amount of inducer, generally in the range of 30–150 μm.

[0094] Step 502 involves constructing a semiconductor nanostructure on the surface of metal nanowires using an in-situ growth method, forming a Schottky heterojunction composite material of metal nanowires and semiconductor nanostructures. Specifically, the metal nanowires prepared in step 501 are dispersed in a reaction solution containing a semiconductor precursor. In-situ growth processes such as hydrothermal, solvothermal, or chemical bath deposition are used to allow the semiconductor nanostructure to directly nucleate and grow directionally on the surface of the metal nanowires. Taking titanium dioxide (TiO2) nanostructures as an example, silver nanowires are dispersed in a hydrothermal reaction solution containing a titanium source precursor (e.g., tetrabutyl titanate or isopropyl titanate), and a hydrothermal reaction is carried out at a certain temperature. During the reaction, the titanium source precursor hydrolyzes and condenses on the surface of the silver nanowires to form TiO2 nuclei. Subsequently, TiO2 nanorods grow radially outwards using the silver nanowires as templates, ultimately forming an AgNWs@ULTiO2 Schottky heterojunction composite material with a sea urchin-like three-dimensional composite morphology. At the direct interface between silver nanowires and TiO2 nanorods, a Schottky barrier and a built-in electric field spontaneously form due to the Fermi level difference between silver (work function approximately 4.26 eV) and anatase TiO2 (work function approximately 4.2 eV, conduction band position approximately -0.5 V vsNHE). After the reaction, the product was collected by centrifugation and washing, and then dried and stored at low temperature. It should be noted that the above-mentioned in-situ growth method is not limited to hydrothermal methods; solvothermal methods and chemical bath deposition methods can also achieve the in-situ construction of semiconductor nanostructures on the surface of metal nanowires.

[0095] Step 503 involves dispersing the composite material in a prepolymer solution containing a rigid polymer backbone precursor and a hydrophilic polymer. Specifically, an aqueous solution containing a rigid polymer backbone precursor (such as PVA) and a hydrophilic polymer (such as PVP) is first prepared as the prepolymer solution base. The rigid polymer backbone precursor is dissolved in deionized water under heating conditions. After complete dissolution, the solution is cooled to room temperature, and the hydrophilic polymer is added and stirred until homogeneous. Subsequently, the Schottky heterojunction composite material (such as AgNWs@ULTiO2) obtained in step 502 is added to the prepolymer solution. Mechanical stirring and ultrasonic dispersion are used to ensure that the composite material is uniformly distributed in the prepolymer solution without agglomeration. The mass concentration of the composite material in the prepolymer solution can be adjusted according to the required conductivity and photoelectric response intensity, generally in the range of 0.5~10 mg / mL. After dispersion, the prepolymer solution is degassed to remove air bubbles, obtaining a homogeneous precursor mixture suitable for microneedle molding.

[0096] Step 504: The prepolymer liquid containing the composite material is filled into the microneedle mold, and a microneedle array with a swellable double-network hydrogel microneedle matrix is ​​formed through a crosslinking process. Specifically, a precision polydimethylsiloxane (PDMS) mold or a silicon mold with the required microneedle shape and size is selected. The prepolymer liquid prepared in step 503 is slowly poured or dripped onto the mold surface, and then vacuum treatment is performed under vacuum conditions to ensure that the prepolymer liquid fully fills the microneedle cavity of the mold under negative pressure, ensuring that each conical cavity is completely filled without leaving air bubbles. After vacuuming, prepolymer liquid is added on top of the mold to form the base layer of the microneedles. Subsequently, the mold filled with prepolymer liquid is crosslinked. The crosslinking process can use physical crosslinking methods, such as room temperature drying hydrogen bonding crosslinking or freeze-thaw cycle crosslinking. Taking the room-temperature drying hydrogen bond crosslinking method as an example, the mold is placed in a constant temperature and humidity environment and slowly dried at room temperature for 24-48 hours. During this process, microcrystalline regions are spontaneously formed between polymer chain segments (such as PVA segments) through hydrogen bonding, constructing a rigid framework for the dual-network hydrogel. After crosslinking is completed, the molded microneedle array is carefully demolded from the mold to obtain a swellable dual-network hydrogel microneedle array with Schottky heterostructure composite material embedded inside. The demolded microneedle array can be stored for a long time under dry and sealed conditions and can be directly applied to the skin surface when needed.

[0097] The photoelectrochemical sensing microneedles of this embodiment can be prepared by following steps 501 to 504 above. The resulting microneedle array has sufficient puncture strength in a dry state, and can quickly establish a sampling-detection interface after being inserted into the skin and absorbing water and swelling. Moreover, the internal three-dimensional conductive network maintains continuity in the swollen state.

[0098] The following describes several optional improvements to the preparation method of this embodiment.

[0099] In some alternative implementations, the silver nanowires in step 501 can be prepared using a polyol method. Specifically, polyvinylpyrrolidone (PVP, molecular weight approximately 1,300,000) is dissolved in ethylene glycol (EG) medium and stirred until completely dissolved in an oil bath at 130°C. Subsequently, a trace amount of ferric chloride (FeCl3) is introduced into the solution as a crystal form inducer. The chloride ions in FeCl3 preferentially adsorb onto the {100} crystal planes of the silver nanocrystals, inhibiting their lateral growth and promoting axial growth. <110> The growth exhibits longitudinal anisotropy. After the inducing agent is completely dissolved, a solution of silver nitrate (AgNO3) in ethylene glycol is slowly added dropwise, and the reaction is continued at 130°C for 5 hours. During the reaction, ethylene glycol acts as both a solvent and a mild reducing agent, promoting the growth of Ag... + The ions are slowly reduced to Ag. 0 Atoms are deposited on the surface of PVP-protected nanocrystal seeds. After the reaction, free PVP and byproducts are removed by repeated centrifugation and washing, finally yielding ultralong silver nanowires with a length of approximately 80 μm and a diameter of approximately 60–100 nm. It should be noted that the halide salt inducer is not limited to FeCl3; other halide salts such as sodium chloride (NaCl), potassium chloride (KCl), or copper chloride (CuCl2) can also be used. Those skilled in the art can flexibly adjust the amount of halide salt according to the target length and diameter of the nanowires. Besides the polyol method, silver nanowires can also be prepared by other methods such as seed-mediated growth and template methods.

[0100] As a preferred but not mandatory method for implementing step 502, the in-situ growth method can be a hydrothermal method. Specifically, the silver nanowires prepared in step 501 are dispersed in a hydrothermal reaction solution containing tetrabutyl titanate (TBT) as a titanium source precursor. Acetylacetone (ACAC) and disodium ethylenediaminetetraacetate (EDTA-Na2) may also be added to the reaction solution as a hydrolysis control agent and a morphology modifier, respectively. The reaction solution is transferred to a polytetrafluoroethylene-lined hydrothermal reactor and reacted at 180–220°C for 12–24 hours. Under hydrothermal conditions, TBT hydrolyzes on the surface of the silver nanowires and forms anatase TiO2 nuclei through heterogeneous nucleation. Subsequently, the TiO2 grows along specific crystal planes into nanorod-like structures, radiating outwards from the silver nanowires as the axis. ACAC controls the hydrolysis rate of TBT through complexation, avoiding excessively rapid homogeneous nucleation that causes TiO2 particles to form independently in the solution rather than grow on the surface of silver nanowires; EDTA-Na2 regulates the growth orientation of TiO2 through selective adsorption, promoting the formation of nanorod-like morphology.

[0101] The hydrothermal reaction temperature has a significant impact on the crystallinity, morphology, and interfacial quality of the Schottky heterostructure of titanium dioxide nanostructures. At lower reaction temperatures (e.g., approximately 180°C in one embodiment), the hydrolysis-condensation rate of TBT is relatively mild, the heterogeneous nucleation process of TiO2 nuclei on the silver nanowire surface is slower and more uniform, the grown nanorods are relatively short and thin, and the radiation density of the urchin-like composite morphology is relatively sparse, but the nanorods exhibit good uniformity of adhesion to the silver nanowire surface. At higher reaction temperatures (e.g., approximately 220°C in one embodiment), the hydrolysis-condensation reaction rate accelerates, the growth rate of TiO2 nanorods is higher, the resulting nanorods have higher crystallinity and longer length, the urchin-like composite morphology is more abundant and dense, and the interfacial area and number of catalytically active sites of the Schottky heterostructure increase accordingly, which is beneficial for improving the photoelectrochemical response intensity. However, excessively high temperatures may lead to intensified homogeneous nucleation, with some TiO2 particles detaching from the silver nanowire surface to form independently. Within a temperature range of 180–220 °C, TBT can undergo heterogeneous nucleation and directional growth using the surface of silver nanowires as the main nucleation sites, forming a urchin-like composite morphology centered on silver nanowires, and establishing a tight Schottky heterojunction interface between the silver nanowires and TiO2. In a preferred reaction condition, the hydrothermal reaction temperature is 200 °C and the reaction time is 18 hours, which achieves a good balance between the crystallinity of the nanorods, morphological uniformity, and the quality of the heterojunction interface.

[0102] After the reaction is complete, the mixture is allowed to cool naturally to room temperature. The product is collected and washed several times alternately with deionized water and anhydrous ethanol to obtain the urchin-like AgNWs@ULTiO2 composite material. Besides the hydrothermal method, in-situ growth of semiconductor nanostructures can also be achieved using a solvothermal method or a chemical bath deposition method. Those skilled in the art can choose the appropriate method based on equipment conditions and material requirements.

[0103] Example 3

[0104] This embodiment provides a wearable photoelectrochemical monitoring system, such as Figure 2 As shown, this system integrates the photoelectrochemical sensing microneedles described in Example 1 onto a flexible patch platform, realizing a closed-loop end-to-end process from interstitial fluid sampling and photoelectrochemical detection to wireless signal transmission. The overall architecture and components of this system are described in detail below.

[0105] I. Flexible Patch Substrate

[0106] The flexible patch substrate serves as the carrier platform for the entire wearable monitoring system, and it is a thin film substrate with good flexibility and skin adhesion. This substrate material can be selected from flexible polymer films such as thermoplastic polyurethane (TPU), polydimethylsiloxane (PDMS), or polyimide (PI). The thickness of the flexible patch substrate is generally in the range of 50~500μm, balancing mechanical strength and wearing comfort. The upper surface of the substrate supports the microneedle sensor array, light source module, signal acquisition and processing module, and their interconnecting circuits; the lower surface of the substrate is attached and fixed to the skin surface using medical tape or a biocompatible adhesive layer.

[0107] II. Microneedle Sensor Array

[0108] The microneedle sensing array is disposed on a flexible patch substrate and includes at least a working electrode microneedle and a counter electrode and a reference electrode that are insulated from it, constituting a complete three-electrode electrochemical detection system. The working electrode microneedle adopts the photoelectrochemical sensing microneedle described in Example 1, namely, a swellable double-network hydrogel microneedle with a metal nanowire / semiconductor nanostructure Schottky heterojunction composite material embedded inside, namely PVA microneedle 206. The counter electrode and the reference electrode can be prepared using materials and processes different from those of the working electrode, and their functions are to provide a current loop and a stable reference potential, respectively. For example, the counter electrode and the reference electrode can be made of polystyrene resin or other rigid polymer materials to obtain a microneedle structure using the same molding process as the working electrode. Then, a conductive layer (such as a chromium / gold bilayer film) and a reference layer (such as Ag / AgCl slurry) are sequentially deposited on the surface of the microneedle by magnetron sputtering, evaporation, or dip coating to realize the conductive function of the counter electrode and the potential reference function of the reference electrode, respectively, forming Ag / AgCl microneedle 207. The working electrode microneedle is kept insulated from the counter electrode and reference electrode on the patch substrate, and each electrode is led out to the signal acquisition and processing module through conductive circuits printed on the substrate.

[0109] III. Light Source Module

[0110] A light source module 203 is mounted on a flexible patch substrate and configured to provide excitation light to the interior of the microneedle sensing array. The core function of this light source module is to provide energy input to the Schottky heterojunction in the working electrode microneedles to excite the LSPR effect of the metal nanowires and generate hot electrons. The light source module can be selected from light-emitting diodes (LEDs), micro-laser diodes, or organic light-emitting diodes (OLEDs), and is electrically connected to the flexible patch substrate. The emission wavelength of the light source should be selected to match the LSPR absorption peak of the metal nanowires. The light source module is mounted on the patch substrate near the working electrode microneedle array, and its optical path is designed to effectively irradiate the Schottky heterojunction active layer inside the microneedles.

[0111] IV. Signal Acquisition and Processing Module

[0112] The signal acquisition and processing module is electrically connected to the microneedle sensor array and is configured to acquire the photocurrent signal output by the working electrode microneedles under zero or low bias voltage, and convert this photocurrent signal into concentration data of the target analyte. The core functions of this module include: applying a constant bias voltage to the working electrode (0V or a bias voltage with an absolute value less than 0.3V in this system); converting the weak photocathode current generated by the working electrode into a quantifiable voltage signal; amplifying, filtering, and performing analog-to-digital conversion on the signal; and converting the processed electrical signal into the concentration value of the target analyte using a preset calibration algorithm. The signal acquisition and processing module can be implemented based on integrated circuit chips or discrete component circuits. Its specific architecture includes a potentiostat circuit, a signal amplification circuit (such as a transimpedance amplifier), an analog-to-digital converter, and a microcontroller unit. The microcontroller unit is responsible for executing the timing control of data acquisition, the signal processing algorithm, and the concentration conversion program, and can output the calculated concentration data to an external display device or mobile terminal via a wired or wireless interface.

[0113] In summary, the wearable photoelectrochemical monitoring system of this embodiment integrates a microneedle sensor array, a light source module, and a signal acquisition and processing module on a flexible patch substrate. It achieves interstitial fluid sampling through minimally invasive puncture of PVA microneedles 206, generates photoelectrochemical reactions by exciting Schottky heterojunctions through the light source module 203, and realizes the conversion and output of photocurrent signals into concentration data through the signal acquisition and processing module, thus forming a closed-loop monitoring platform of "sampling-identification-processing".

[0114] The following describes several optional improvements to the system in this embodiment.

[0115] In some optional implementations, the light source module 203 can employ a micro-LED array. When the metal nanowires in the working electrode microneedles are silver nanowires, the LSPR absorption peak of silver nanowires is located in the visible light range (approximately 400-500 nm). Therefore, blue or white LEDs with an emission wavelength of approximately 450 nm can be selected as the excitation source. The LED array consists of multiple micro-LED chips arranged at uniform intervals around or above the working electrode microneedle array, ensuring that each PVA microneedle 206 receives sufficient and uniform excitation light irradiation. The brightness and switching frequency of the LEDs can be programmed and controlled by the microcontroller unit in the signal acquisition and processing module to achieve an intermittent excitation mode (e.g., turning on the LEDs for detection at regular intervals), thereby reducing system power consumption and extending battery life.

[0116] As a preferred but not essential improvement, the signal acquisition and processing module can be mounted on the flexible electronic system 202. The flexible electronic system 202 is based on a flexible printed circuit board (FPCB), which integrates a potentiostat circuit, a transimpedance amplifier, and a microcontroller unit with integrated Bluetooth Low Energy (BLE) communication capabilities. Taking the nRF52840 Bluetooth SoC (System on Chip) as an example, this chip integrates an ARM Cortex-M4F core processor, a Bluetooth 5.0 wireless communication module, a multi-channel analog-to-digital converter (ADC), and various low-power peripheral interfaces, enabling it to perform all tasks of data acquisition, signal processing, and wireless transmission on a single chip. The potentiostat circuit maintains a precise zero-bias voltage or preset bias voltage between the working electrode and the counter / reference electrode. The transimpedance amplifier converts the weak photocathode current (typically in the nanoamp to microamp range) output from the working electrode into a voltage signal that can be quantized by the ADC. The microcontroller unit executes a chronoamperometry program, continuously sampling photocurrent values ​​within a preset time window after the excitation light is turned on, and converts the current values ​​into the concentration of the target analyte using a built-in calibration curve algorithm. The converted concentration data is wirelessly packaged into a JSON data packet via Bluetooth connection 208 and sent to a paired smartphone or tablet mobile terminal 209. The working electrode microneedles (PVA microneedles 206), counter electrode, and reference electrode (Ag / AgCl microneedles 207) are connected to the signal acquisition and processing module on the flexible electronic system 202 via silver paste conductive circuits screen-printed on a flexible patch substrate (TPU layer 205). The screen printing process can quickly and cost-effectively form fine conductive circuit patterns on a flexible substrate, achieving a reliable electrical connection between the microneedle electrodes and the circuits on the flexible electronic system 202. The system also includes a silicone layer 204 (i.e., a flexible protective layer) covering the flexible electronic system 202. This silicone layer 204 is made of flexible insulating materials such as silicone rubber or PDMS to protect the circuitry from sweat, moisture, and mechanical damage, while maintaining the overall flexibility and wearing comfort of the patch. The entire system is powered by a lithium-ion battery 201, and the overall weight can be controlled to approximately 2.57 g, achieving an ultra-lightweight wearable experience. In addition to Bluetooth Low Energy connectivity 208, the wireless transmission protocol can also be replaced with other short-range wireless communication methods such as Near Field Communication (NFC) or Wi-Fi.

[0117] Example 4

[0118] This embodiment provides a method for detecting target analytes based on minimally invasive interstitial fluid sampling and in-situ photoelectrochemical recognition, referring to... Figure 3The timeline flowchart shown illustrates that this method mainly includes five steps: microneedle attachment and puncture, interstitial fluid extraction, photoelectric excitation, catalytic oxidation detection, and signal processing. Each step is described in detail below.

[0119] Step 301: The photoelectrochemical sensing microneedle array is attached to the skin surface, allowing it to penetrate the stratum corneum and reach the dermis via a minimally invasive procedure. In this embodiment, the user selects a relatively flat area such as the inner forearm or abdomen as the monitoring location. First, the skin surface is cleaned with an alcohol swab to remove oil and dirt. Then, with the microneedle face of the photoelectrochemical sensing microneedle array facing the skin, even pressure is applied to the top of the patch with a finger, allowing the microneedle array to penetrate the stratum corneum and enter the dermis. The photoelectrochemical sensing microneedle array is made of a swellable dual-network hydrogel. Within this hydrogel, metal nanowires with localized surface plasmon resonance and a high aspect ratio are in situ embedded to form a three-dimensional conductive network. Semiconductor nanostructures are composited on the surface of the metal nanowires, forming Schottky heterojunctions. The microneedles exhibit high rigidity in a dry state and will not bend or break during puncture. The puncture depth of microneedles is determined by the height of the microneedles and the width of the base. Generally, it can penetrate the stratum corneum (about 10~20μm) and part of the epidermis to reach the upper dermis rich in interstitial fluid. During the puncture process, the user only feels a slight tingling sensation and no obvious pain. After application, the patch is firmly attached to the skin surface by a biocompatible adhesive layer on a flexible base.

[0120] Step 302 involves extracting subcutaneous interstitial fluid into the photoelectrochemical sensing microneedle array through the swelling effect of the swellable dual-network hydrogel. After penetrating the stratum corneum, the microneedles' tips directly contact the interstitial fluid in the dermis. An osmotic pressure difference exists between the hydrophilic polymer network in the hydrogel microneedle matrix and the interstitial fluid. Driven by this osmotic pressure difference and capillary forces, water molecules and target analyte molecules (such as uric acid and electrolytes) in the interstitial fluid passively diffuse into the porous network structure of the microneedle matrix. The microneedle matrix swells after absorbing water, a process that lasts approximately 60 seconds to 15 minutes until swelling equilibrium is reached. During the swelling process, the three-dimensional conductive network maintains the continuity of electron transport channels through flexible overlap between the wires, under the mechanical constraint of the rigid polymer skeleton in the hydrogel and the synergistic effect of the high aspect ratio of the metal nanowires. The rigid polymer framework's microcrystalline regions constrain the hydrogel's maximum expansion, while the high aspect ratio metal nanowires adapt to volume changes during matrix deformation through bending and slippage, maintaining the overlap between adjacent nanowires. This synergistic mechanism ensures that even with significant swelling of the microneedles (e.g., 125% swelling rate), the internal conductive network maintains a low-impedance electron transport pathway, providing a reliable electrical basis for subsequent photoelectrochemical detection.

[0121] Step 303: The Schottky heterojunction is excited by a light source. Based on the plasmon resonance effect, the metal nanowires generate hot electrons. Driven by the built-in electric field of the Schottky heterojunction, these hot electrons migrate to the surface of the semiconductor nanostructure and react with dissolved oxygen to generate reactive oxygen species (ROS). After the microneedles swell to sampling equilibrium, the system control circuit activates the light source module to provide excitation light to the active layer of the Schottky heterojunction inside the microneedles. Photons of a specific wavelength emitted by the light source are incident on the surface of the metal nanowires, exciting the surface free electrons to undergo collective oscillation, i.e., localized surface plasmon resonance (LSPR). The LSPR effect efficiently converts light energy into high-energy hot electrons in the metal nanowires. The energy of these hot electrons exceeds the height of the Schottky barrier between the metal and semiconductor, and driven by the built-in electric field, they cross the barrier and are unidirectionally injected from one side of the metal nanowire into the conduction band of the semiconductor nanostructure. The electrons injected into the semiconductor surface are in a high-energy excited state and have strong reducing power, subsequently reacting with oxygen molecules dissolved in the interstitial fluid inside the microneedles. A reduction reaction occurs, reducing molecular oxygen to reactive oxygen species (ROS). This reaction can be represented as follows: (Superoxide radicals). Reactive oxygen radicals, as highly reactive intermediates, adsorb or remain on the surface catalytic sites of semiconductor nanostructures, waiting to undergo oxidation reactions with target analyte molecules that diffuse to these sites from the interstitial fluid.

[0122] Step 304: Reactive oxygen species (ROS) perform in-situ specific non-enzymatic catalytic oxidation of the target analyte in the interstitial fluid under zero or low bias voltage conditions, generating a photocurrent signal related to the target analyte concentration. In this step, the target analyte molecules, which have diffused to the vicinity of the semiconductor nanostructure surface via the hydrogel network, come into contact with the ROS generated in step 303 and undergo an oxidation reaction. This oxidation reaction is a non-enzymatic catalytic process, involving no biological enzymes, and is therefore unaffected by enzyme inactivation, enzyme loss, or batch-to-batch differences. During the reaction, the target analyte molecules are oxidized, contributing electrons to the semiconductor surface. These electrons flow from the working electrode to the counter electrode through an external circuit, forming a detectable photocathode current. Since the above photoelectrochemical reaction is entirely driven by the LSPR hot electrons and the built-in electric field of the Schottky junction, the system can generate a significant photocurrent signal under zero bias voltage (0V) or low bias voltage conditions without the need to apply a high oxidation bias voltage. The magnitude of the photocathode current follows a certain quantitative relationship with the concentration of the target analyte: within the detection range, as the concentration of the target analyte in the interstitial fluid increases, the number of analyte molecules participating in the oxidation reaction increases, and the resulting photocathode current increases accordingly.

[0123] Step 305: Acquire and process the photocurrent signal to obtain the concentration information of the target analyte. The potentiostat circuit in the signal acquisition and processing module maintains a zero bias or preset bias voltage between the working electrode and the reference electrode. The transimpedance amplifier converts the weak photocathode current output by the working electrode into a voltage signal in real time. The microcontroller unit executes a timing current analysis program, continuously sampling the photocurrent within a preset time window after the light source is turned on (e.g., 10-30 seconds after illumination begins), extracting the steady-state photocurrent value or the photocurrent variation amplitude as the analysis signal. The microcontroller unit pre-stores a calibration curve established through standard solution calibration. This calibration curve describes the correspondence between the photocurrent signal value and the concentration of the target analyte, typically in a linear form. (in Photocurrent, For the target analyte concentration, This is the sensitivity coefficient. The baseline intercept is used (or a logarithmic linear relationship is used). The microcontroller converts the collected photocurrent values ​​into the concentration of the target analyte based on the calibration curve. Finally, the concentration data can be transmitted to a mobile terminal for display and storage via a wireless communication module, or it can be recorded in local memory. The above detection process can be set to run periodically, with a detection cycle typically ranging from 20 minutes to 1 hour, to achieve continuous dynamic monitoring of the target analyte concentration.

[0124] Through steps 301 to 305 above, this embodiment realizes a complete detection process from microneedle minimally invasive adhesion, passive extraction of interstitial fluid, photoelectrochemical excitation and catalytic oxidation, to signal acquisition and processing. This method requires no blood sampling throughout the entire process, the sampling process is minimally invasive and painless, the detection process does not rely on biological enzymes and can operate at zero bias voltage, exhibiting high selectivity and long-term stability.

[0125] Example 5

[0126] Based on Examples 1 to 4, this embodiment uses uric acid (UA) as the target analyte, AgNWs@ULTiO2 Schottky heterojunction as the photosensitive recognition material, and PVA / PVP (mass ratio 100:1.25) as the dual-network hydrogel matrix material to comprehensively verify the detection performance of the photoelectrochemical sensing microneedle system in a simulated interstitial fluid environment and a live skin model.

[0127] I. In vitro detection performance verification

[0128] First, the uric acid detection performance of the AgNWs@ULTiO2 hydrogel photoelectrode was characterized in a standard phosphate buffer solution (PBS, pH 7.4). A miniature LED (wavelength 450 nm, power density approximately 20 mW / cm²) was used for the measurement. 2Using a photocathode as the excitation source, and under a 0V bias voltage, the photocathode current response corresponding to different concentrations of uric acid solutions was recorded by chronoamperometry. Experimental results show that within the uric acid concentration range of 10–1000 μM, there is a good linear relationship between the photocathode current value and the uric acid concentration, with the linear regression equation being: linear correlation coefficient The limit of detection (LOD) is 2.4 μM ( The physiological concentration range of uric acid in human subcutaneous interstitial fluid is approximately 100–400 μM. Therefore, the linear detection range and sensitivity of this sensing system can fully meet the requirements for quantitative detection of uric acid under physiological conditions.

[0129] Subsequently, the anti-interference selectivity of the sensing microneedles was systematically evaluated. High concentrations of ascorbic acid (AA, 500 μM), dopamine (DA, 50 μM), glucose (18 mM, simulating blood glucose levels in hyperglycemic patients), creatinine (200 μM), and urea (5 mM), all common interstitial fluid substances, were sequentially added to a PBS buffer containing 200 μM uric acid. The results showed that the addition of these interfering substances did not cause significant changes in the photocathode current (current fluctuation < 3%), but upon subsequent addition of 200 μM uric acid, the photocurrent signal exhibited a response jump equal to the initial amount. These results confirm that the sensing system possesses excellent selective recognition capability for uric acid under 0V bias, effectively eliminating the influence of common interfering substances in the physiological environment.

[0130] II. Long-term stability verification

[0131] To verify the long-term operational stability of the sensing microneedles, the AgNWs@ULTiO2 hydrogel photoelectrode was continuously immersed in a simulated interstitial fluid (PBS buffer containing 150 mM NaCl, 4.5 mM KCl, 2.5 mM CaCl2, 200 μM UA, and 500 μM AA) at 37°C, and periodic measurements were performed. The same electrode was measured three times weekly with a uric acid standard solution, and the photocurrent response was recorded. Experimental results showed that after 7 weeks of continuous monitoring, the photocurrent signal attenuation rate of the sensing microneedles was less than 5%, and the slope of the calibration curve remained within an acceptable range. This long-term stability is attributed to two factors: First, the AgNWs@ULTiO2 heterojunction is an all-inorganic material system, containing no easily mutated components such as biological enzymes, and its tolerance to temperature and pH is far superior to that of enzyme sensors; Second, the anti-swelling design of the PVA / PVP dual-network hydrogel ensures the structural stability of the three-dimensional conductive network under long-term immersion and swelling conditions, and the overlapping pathways of the silver nanowires do not undergo irreversible breakage due to repeated swelling and contraction of the hydrogel.

[0132] III. Verification of Viviparous Skin Puncture and Interstitial Fluid Sampling

[0133] Reference Figure 4 The puncture performance and interstitial fluid sampling capability of the microneedle patch were validated in a rat skin model. A dried PVA / PVP dual-network hydrogel microneedle array was attached to the shaved skin surface of the rat's back and secured with gentle pressure applied by fingers. After puncture, a clear array of micro-needles corresponding to the microneedle arrangement was observed on the skin surface in the area where the microneedle array was removed, confirming successful penetration of the stratum corneum. The needle marks on the skin surface completely disappeared within 24 hours after puncture, and no adverse reactions such as redness, swelling, inflammation, or infection were observed, indicating that the minimally invasive puncture has good safety and tissue recovery capabilities. Simultaneously, analysis of the interstitial fluid components absorbed by the swollen microneedles revealed the presence of uric acid, glucose, sodium ions, and potassium ions, with concentrations less than 8% different from those of directly extracted interstitial fluid samples, validating the representativeness of the hydrogel microneedles in interstitial fluid sampling.

[0134] IV. Dynamic monitoring of uric acid in a chronic kidney disease model

[0135] Furthermore, the practical application capability of the wearable monitoring system was validated in a rat model of chronic kidney disease (CKD). A CKD rat model was established using a 5 / 6 nephrectomy, and the serum uric acid levels in the model animals were significantly higher than those in the normal control group. The wearable photoelectrochemical monitoring patch of this application was worn on the dorsal skin of the CKD model rats. The system automatically performed a detection cycle every 30 minutes (including LED excitation, photocurrent acquisition, and concentration conversion), and transmitted the data in real time to the paired receiving terminal via Bluetooth. During a continuous 72-hour monitoring period, the system successfully tracked the dynamic fluctuations in uric acid levels in the CKD rats, including the peak uric acid concentration after feeding and the decreasing trend after drug intervention. The uric acid concentration data obtained by the microneedle monitoring system was compared with the results of simultaneous venous blood sampling and biochemical analysis. The Pearson correlation coefficient between the two sets of data was... The root mean square error (RMSE) was less than 15 μM, confirming the detection accuracy and clinical reference value of this system in complex metabolic disease models.

[0136] Furthermore, the biocompatibility of the AgNWs@ULTiO2 active material in the microneedles was evaluated. After use, the microneedles were immersed in simulated interstitial fluid for 48 hours, and the concentration of silver ions in the immersion solution was detected by inductively coupled plasma mass spectrometry (ICP-MS). The results showed that the leaching amount of silver ions was extremely low, far below the biocompatibility threshold specified by international standards. This indicates that the physical cross-linking structure of the PVA / PVP dual-network hydrogel effectively locks the nanomaterials within the microneedle matrix, preventing the active material from penetrating and leaking into human tissues, thus ensuring biocompatibility during wear.

[0137] It should be noted that, in this application, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such a process, method, article, or apparatus. Without further limitations, an element defined by the phrase "comprising one" does not exclude the presence of other identical elements in the process, method, article, or apparatus that includes said element. In this application, if it refers to performing an action according to a certain element, it means performing the action at least according to that element, including two cases: performing the action only according to that element, and performing the action according to that element and other elements. Expressions such as "multiple," "repeatedly," and "various" include two, two times, two kinds, and more than two, more than two times, and more than two kinds.

[0138] This specification includes combinations of various embodiments described herein. Individual references to embodiments (e.g., “one embodiment”, “some embodiments”, or “preferred embodiments”) do not necessarily refer to the same embodiment; however, these embodiments are not mutually exclusive unless indicated to be mutually exclusive or are readily apparent to those skilled in the art. It should be noted that the word “or” is used in a non-exclusive sense throughout this specification unless the context explicitly indicates or requires it.

Claims

1. A photoelectrochemical sensing microneedle, characterized in that, include: A swellable dual-network hydrogel microneedle matrix comprising a rigid polymer backbone providing mechanical constraint and a hydrophilic polymer network providing fluid absorption capability, configured to undergo constrained volume swelling upon insertion into the skin and absorption of interstitial fluid; A three-dimensional conductive network is in situ embedded inside the swellable dual-network hydrogel microneedle matrix. The three-dimensional conductive network is composed of interconnected metal nanowires with localized surface plasmon resonance effect and high aspect ratio. A semiconductor nanostructure is composited on the surface of the metal nanowire and forms a Schottky heterojunction with the metal nanowire at the contact interface. The mechanical constraint of the rigid polymer skeleton and the high aspect ratio of the metal nanowires are configured in a synergistic way to maintain the physical overlap between adjacent metal nanowires when the swellable dual-network hydrogel microneedle matrix undergoes volume swelling, so as to maintain the continuity of electron transport in the three-dimensional conductive network. Under excitation light irradiation, the metal nanowires generate hot electrons based on the localized surface plasmon resonance effect. Driven by the built-in electric field of the Schottky heterojunction, the hot electrons migrate to the semiconductor nanostructure and generate reactive oxygen free radicals to perform non-enzymatic catalytic oxidation of the target analyte in the interstitial fluid inside the matrix at a bias voltage with an absolute value of less than 0.3V, and generate a photocurrent signal.

2. The photoelectrochemical sensing microneedle according to claim 1, characterized in that, The swellable dual-network hydrogel microneedle matrix is ​​a physically cross-linked dual-network hydrogel composed of polyvinyl alcohol and polyvinylpyrrolidone, wherein the mass ratio of polyvinyl alcohol to polyvinylpyrrolidone is 100:(0.5~5). The microcrystalline regions formed by the polymer chains of polyvinyl alcohol during the physical cross-linking process constitute the rigid polymer skeleton, which provides puncture force to penetrate the stratum corneum of the skin in a dry state and limits excessive expansion in a wet state. The polyvinylpyrrolidone forms the hydrophilic polymer network and is dispersed in the gaps of the microcrystalline region, which is used to form an osmotic pressure difference with the interstitial fluid to drive the body fluid to diffuse into the microneedles.

3. The photoelectrochemical sensing microneedle according to claim 1, characterized in that, The metal nanowires are silver nanowires with a length of 30~150μm; the semiconductor nanostructure is a titanium dioxide nanostructure, which is in the form of nanorods and grows in situ in a radial pattern centered on the silver nanowires, forming a sea urchin-like composite morphology with a large three-dimensional specific surface area.

4. The photoelectrochemical sensing microneedle according to any one of claims 1 to 3, characterized in that, The target analyte is uric acid, and the reactive oxygen species is superoxide radical. The non-enzymatic catalytic oxidation specifically includes: the hot electrons that migrate directionally to the surface of the semiconductor nanostructure undergo a reduction reaction with dissolved oxygen molecules to generate superoxide radicals, and the superoxide radicals are used to specifically oxidize uric acid into allantoin under zero bias voltage, so as to avoid the co-oxidation interference of electroactive substances coexisting in the interstitial fluid from a thermodynamic perspective.

5. The photoelectrochemical sensing microneedle according to claim 1, characterized in that, The height of a single microneedle in the microneedle matrix is ​​800~1500μm, and the width of the matrix is ​​300~600μm; the breaking force of a single microneedle in the microneedle matrix under dry conditions is greater than 0.4 N.

6. A wearable photoelectrochemical monitoring system, characterized in that, include: Flexible patch substrate; A microneedle sensing array, disposed on the flexible patch substrate, includes at least a working electrode microneedle and a counter electrode and a reference electrode that are insulated and isolated therefrom, wherein the working electrode microneedle is a photoelectrochemical sensing microneedle as described in any one of claims 1 to 5. A light source module, disposed on the flexible patch substrate, is configured to provide the excitation light to the interior of the microneedle sensing array; and The signal acquisition and processing module is electrically connected to the microneedle sensing array and is configured to acquire the photocurrent signal output by the working electrode microneedle under a bias voltage with an absolute value of less than 0.3V, and convert the photocurrent signal into concentration data of the target analyte.

7. The wearable photoelectrochemical monitoring system according to claim 6, characterized in that, The light source module includes a miniature light-emitting diode array; The signal acquisition and processing module is mounted on a flexible printed circuit board and includes a potentiostat circuit, a transimpedance amplifier, and a microcontroller unit with integrated low-power Bluetooth communication functionality. The working electrode microneedle, the counter electrode, and the reference electrode are connected to the signal acquisition and processing module via conductive circuits screen-printed on the flexible patch substrate; The system also includes a flexible protective layer covering the flexible printed circuit board.

8. A method for preparing a photoelectrochemical sensing microneedle according to any one of claims 1 to 5, characterized in that, Includes the following steps: Fabrication of high aspect ratio metal nanowires with localized surface plasmon resonance effect; Semiconductor nanostructures were constructed on the surface of the metal nanowires by in-situ growth, forming a Schottky heterojunction composite material of metal nanowires and semiconductor nanostructures. The composite material is dispersed in a prepolymer solution containing a rigid polymer backbone precursor and a hydrophilic polymer; A prepolymer containing the composite material is filled into a microneedle mold and then formed into a microneedle array with a swellable dual-network hydrogel microneedle matrix through a crosslinking process.

9. The preparation method according to claim 8, characterized in that, The metal nanowires are silver nanowires, which are prepared by the polyol method by reacting polyvinylpyrrolidone and silver nitrate in ethylene glycol medium and introducing halide salts as crystal inducing agents. The in-situ growth method is a hydrothermal method, in which the silver nanowires are dispersed in a hydrothermal reaction solution containing a titanium source precursor and reacted at 180~220℃, so that the titanium dioxide nanostructure grows in a directional manner with the silver nanowires as a template to form a sea urchin-like composite morphology.

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