Preparation method of pluggable microneedle electrode array

Abstract

The invention discloses a preparation method of a pluggable microneedle electrode array. The method comprises the following steps of: providing an array bottom plate which is fixedly provided with microneedle insertion holes; a detachable connecting structure is arranged in the microneedle insertion hole; assembling a plurality of micro-needle electrodes and a micro connector into a micro-needle connector; the microneedle connectors are embedded into the microneedle insertion holes through the detachable connection structures, and the pluggable microneedle electrode array is formed by the microneedle connectors and the array bottom plate. According to the embodiment of the invention, the detachable installation of the microneedle electrode is realized through the detachable connection structure, the replacement of the microneedle electrode in the detection process is facilitated, and the convenience is improved. Meanwhile, according to the embodiment of the invention, the microneedle array is prepared in a conventional preparation mode, and the cost is controllable. Therefore, the preparation method provided by the embodiment of the invention is beneficial to reducing the cost and improving the convenience. The method can be widely applied to the technical field of electrochemical detection.

Description

Technical Field

[0001] The invention relates to the technical field of electrochemical detection, in particular to a method for preparing a pluggable microneedle electrode array. Background Art

[0002] In related technologies, microneedle arrays often use an integrated design, such as photolithography, micromolding, and 3D printing. In actual testing and applications, if the function of one electrode in the microneedle array is damaged, the entire microneedle array may fail or be unable to achieve all functions. This results in a low fault tolerance and lack of convenience when the microneedle array is used for detection. On the other hand, the integrated microneedle array design is also difficult to control in large-scale batch production. In particular, photolithography technology involves complex, multi-step and expensive procedures, and the extremely high machine prices of precision 3D printing have a great impact on the cost control of microneedle preparation. Summary of the invention

[0003] The purpose of the present invention is to solve one of the technical problems existing in the prior art to at least a certain extent.

[0004] Therefore, the object of the present invention is to provide a low-cost method for preparing a pluggable microneedle electrode array.

[0005] In order to achieve the above technical objectives, the technical solutions adopted by the embodiments of the present invention include:

[0006] On the one hand, an embodiment of the present invention provides a method for preparing a pluggable microneedle electrode array, comprising the following steps:

[0007] The method for preparing a pluggable microneedle electrode array according to an embodiment of the present invention comprises: providing an array base plate, on which a microneedle socket is fixed; a detachable connection structure is installed inside the microneedle socket; assembling a plurality of microneedle electrodes and a microconnector into a microneedle connector; embedding the microneedle connector into the microneedle socket through the detachable connection structure to form a pluggable microneedle electrode array with the array base plate. The embodiment of the present application realizes the detachable installation of the microneedle electrode through the detachable connection structure, which is convenient for replacing the microneedle electrode during the detection process and is conducive to improving convenience. At the same time, the embodiment of the present application prepares the microneedle array through a conventional preparation method, and the cost is controllable. Therefore, the preparation method provided in the embodiment of the present application is conducive to reducing costs and improving convenience.

[0008] In addition, the method for preparing the pluggable microneedle electrode array according to the above embodiment of the present invention may also have the following additional technical features:

[0009] Furthermore, the method for preparing the pluggable microneedle electrode array according to the embodiment of the present invention further comprises:

[0010] A shell is customized by 3D printing, and the microneedle electrode passes through the shell to contact the shell with the array bottom plate.

[0011] Further, in one embodiment of the present invention, the microneedle connector is prepared by the following steps:

[0012] Determining that the microneedle electrode is based on a stainless steel needle, performing an acid wash to clean the oxide film of the stainless steel microneedle electrode and electroplating a precious metal to obtain a gold electrode;

[0013] The gold electrode is cut to obtain a size electrode; the size electrode is assembled with the micro connector via a detachable connection structure to obtain a microneedle connector.

[0014] Further, in one embodiment of the present invention, the step of cleaning the oxide film of the stainless steel microneedle electrode with an acid wash solution and electroplating the noble metal to obtain a gold electrode comprises:

[0015] The oxide layer on the surface of the stainless steel microneedle electrode is removed by pickling solution, the treated stainless steel microneedle electrode is fixed on the electrode clip of the working electrode, and immersed in a sodium gold sulfite solution; the counter electrode is a Ag / AgCl reference electrode and a gold sheet;

[0016] According to the ISTEP method, electroplating is performed by a first current for a first time using an electrochemical workstation to form a stable gold layer on the surface of the stainless steel microneedle electrode to obtain a gold electrode; the first current is -1 to -4 mA, and the first time is 400 to 600 seconds.

[0017] Further, in one embodiment of the present invention, the gold electrode is cut to obtain a size electrode; and the size electrode is assembled with the micro connector through a detachable connection structure to obtain a microneedle connector, comprising:

[0018] Putting the gold electrode into the cutting through hole to cut the gold electrode to obtain a size electrode; the height of the cutting through hole is the length of the size electrode;

[0019] Solder paste is put into the hole of the micro joint, and then the size electrode is put into the micro joint, and a welding and fixing operation is performed to obtain a micro needle joint.

[0020] Further, in one embodiment of the present invention, the microneedle electrode comprises a H2O2 sensing electrode, and the H2O2 sensing electrode is prepared by the following steps:

[0021] Fixing the microneedle connector to the electrode holder of the working electrode and immersing it in a platinum sulfite solution;

[0022] Electroplating is performed for a second period of time at a second current using an electrochemical workstation, and after electroplating, the electrode is cleaned using an ultrasonic cleaning device; the electrode cleaning time is 5 to 15 minutes; the second current is -200μA to -400μA, and the second period of time is 100 to 300s.

[0023] Further, in one embodiment of the present invention, the microneedle electrode includes a sensing electrode, and the sensing electrode is prepared by the following steps:

[0024] The microneedle electrode part of the prepared microneedle connector is dipped in an oxidase solution and slowly dried overnight at room temperature to obtain a metabolite oxidase sensing electrode;

[0025] Alternatively, an ion selective membrane is modified on a microneedle electrode modified with a gold layer to obtain an ion sensing electrode.

[0026] Further, in one embodiment of the present invention, the microneedle electrode includes a reference electrode, and the reference electrode is prepared by the following steps:

[0027] The microneedle electrode modified with the gold layer is subjected to a pull coating process in an Ag / AgCl paste and placed in an oven for drying; the temperature of the oven is 70 to 90° C., and the drying time is 1.5 to 2.5 hours;

[0028] The prepared PVB solution is subjected to ultrasonic oscillation treatment, and the dried Ag / AgCl is placed in liquid PVB for stretch coating treatment, and then waits for drying to obtain a reference electrode.

[0029] Further, in one embodiment of the present invention, the microneedle electrode comprises a pH sensing electrode, and the pH sensing electrode is prepared by the following steps:

[0030] The gold-layered microneedle electrode was drawn and coated in a CNT solution and then immersed in a PANI solution;

[0031] The electrochemical workstation was used to perform electroplating using the CV method with 60 segments; the electroplating parameters were -0.1 to 0.8 V, and the scan rate was 0.02 to 0.08 V / s.

[0032] Furthermore, in one embodiment of the present invention, the method further comprises:

[0033] The microneedle array was determined to be arranged in a regular hexagonal shape, the number of the microneedle electrodes was 7, and the center position was the reference electrode.

[0034] On the other hand, an embodiment of the present invention provides a pluggable microneedle electrode array, which is prepared by the above-mentioned method for preparing a pluggable microneedle electrode array.

[0035] On the other hand, an embodiment of the present invention provides a detection device, including the above-mentioned pluggable microneedle electrode array.

[0036] The embodiment of the present invention provides a method for preparing a pluggable microneedle electrode array, the method comprising: providing an array base plate, on which a microneedle socket is fixed; a detachable connection structure is installed inside the microneedle socket; a plurality of microneedle electrodes and a microconnector are assembled into a microneedle connector; the microneedle connector is embedded into the microneedle socket through the detachable connection structure to form a pluggable microneedle electrode array with the array base plate. The embodiment of the present application realizes the detachable installation of the microneedle electrode through the detachable connection structure, which is convenient for replacing the microneedle electrode during the detection process, and is conducive to improving convenience. At the same time, the embodiment of the present application prepares the microneedle array through a conventional preparation method, and the cost is controllable. Therefore, the preparation method provided in the embodiment of the present application is conducive to reducing costs and improving convenience. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the embodiments of the present invention or the drawings of related technical solutions in the prior art are introduced below. It should be understood that the drawings introduced below are only for the convenience of clearly describing some embodiments of the technical solutions of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative work.

[0038] Figure 1 A schematic diagram of the assembly relationship of the microneedle connector provided in an embodiment of the present application;

[0039] Figure 2 A schematic diagram of components of an embodiment of a microneedle electrode substrate provided in the present application;

[0040] Figure 3 A schematic diagram of components of an embodiment of a microneedle electrode modified with a noble metal layer provided in the present application;

[0041] Figure 4 A cross-sectional schematic diagram of an embodiment of a micro connector provided in the present application;

[0042] Figure 5 A schematic diagram of components of an embodiment of a micro connector provided by the present application;

[0043] Figure 6 A schematic diagram of components of another embodiment of a micro connector provided by the present application;

[0044] Figure 7 A schematic diagram of components of an embodiment of a jack provided in the present application;

[0045] Figure 8A schematic diagram of components of an embodiment of the connection between a micro connector and a socket provided by the present application;

[0046] Fig. 9 A schematic diagram of components of an embodiment of an array base plate provided in the present application;

[0047] Fig.10 A schematic diagram of components of an embodiment of fixing the array base plate and the plug hole provided by the present application;

[0048] Fig.11 A schematic diagram of components of an embodiment of a microneedle electrode array provided in the present application;

[0049] Fig.12 A schematic diagram of components of another embodiment of the microneedle electrode array provided in the present application;

[0050] Fig.13 An assembly flow chart of an embodiment of a microneedle electrode array provided in the present application;

[0051] Fig.14 An assembly flow chart of another embodiment of the microneedle electrode array provided in the present application;

[0052] Fig.15 A physical assembly flow chart of an embodiment of a microneedle electrode array provided in the present application;

[0053] Fig.16 A flowchart of an embodiment of a preparation process of a microneedle electrode provided in the present application;

[0054] Fig.17a A flow chart of an embodiment of the preparation process of the gold electrode and the reference electrode provided in the present application;

[0055] Fig.17b A flow chart of an embodiment of the preparation process of the H2O2 electrode and the pH electrode provided in the present application;

[0056] Fig.18 A schematic diagram of an embodiment of electron microscope characterization of a microneedle electrode provided in the present application;

[0057] Fig.19 A schematic diagram of an embodiment of the in vitro performance characterization of the microneedle electrode provided in the present application. DETAILED DESCRIPTION

[0058] The embodiments of the present invention are described in detail below, and examples of the embodiments are shown in the accompanying drawings, wherein the same or similar reference numerals throughout represent the same or similar elements or elements having the same or similar functions. The embodiments described below with reference to the accompanying drawings are exemplary and are only used to explain the present invention, and are not to be construed as limitations of the present invention. For the step numbers in the following embodiments, they are only provided for the convenience of explanation, and the order between the steps is not limited in any way, and the execution order of each step in the embodiment can be adaptively adjusted according to the understanding of those skilled in the art.

[0059] The microneedle electrode array is a device that connects biological subcutaneous tissue with external analysis equipment. Its structure can penetrate the skin, directly contact subcutaneous tissue fluid, and does not cause nerve damage and bleeding. The working principle of the microneedle electrode is to convert the biochemical signals in the tissue fluid into electrical signals that can be collected and processed, thereby realizing the dynamic detection of tissue fluid biomarkers. Tissue fluid is a human body fluid under the skin, which continuously exchanges substances with blood through capillaries. The material composition and content of each component in it are close to those of blood. The detection technology based on tissue fluid is most likely to replace the current gold standard of clinical diagnosis based on blood. Therefore, microneedle electrodes have always been the core device for subcutaneous tissue fluid detection, and have become a powerful tool for biomarker sampling and diagnosis, and have been widely used in healthcare fields such as real-time monitoring and remote care.

[0060] At present, almost all reported microneedle sensors are based on electrochemical sensing methods. Microneedle electrochemical sensors are generally combined with biorecognition elements on microneedles, and can meet high sensitivity and high selectivity. In microneedle electrodes based on electrochemical detection, the recognition process is achieved through the chemical reaction of biomarkers and recognition elements, such as catalysis by oxidase. This process makes the intensity of the electrical signal strongly correlated with the target analyte, thereby achieving quantitative detection. Electrochemical sensing has unique advantages for signal conversion, such as miniaturized design, high speed, low cost, low power consumption, etc., as well as highly scalable manufacturing and easier detection in subcutaneous tissue fluid environments. At present, biosensors based on microneedle arrays are particularly outstanding in multi-parameter system integration and in vivo biomarker analysis through functional modifications, such as biological proteases and ion-selective membranes.

[0061] Compared with sensors used for other alternative body fluids such as sweat and saliva, microneedle electrodes for subcutaneous tissue fluid can provide better signal quality and achieve strong correlation with blood. In order to reduce the damage caused by microneedles breaking the skin, on the one hand, the length of the microneedles and the area of ​​the microneedle array are reduced; on the other hand, the sensing microneedles combined with electrochemical technology are mostly solid or hollow microneedles. In this type of microneedles, the manufacturing method of microneedle electrodes is often based on photolithography technology, micromolding technology, etc. The preparation materials of photolithography technology are often based on silicon substrates and can be used to manufacture hollow, solid and planar microneedle arrays. Micromolding technology is the casting of microneedles through molds, such as molten metal or resin.

[0062] To achieve reliable skin penetration and transdermal sensing, the sharpness and diameter of the microneedle need to be taken into account, and it should be able to penetrate the skin while minimizing pain and skin damage. In addition, safety factors such as the mechanical fracture toughness of the microneedle material, the microneedle stiffness, and the biocompatibility of the material need to be considered. When designing the geometric features of the microneedle, special attention should also be paid to the biomechanical properties of the skin to overcome the offsetting effect of skin elasticity.

[0063] Existing microneedle arrays often use an integrated design, such as photolithography, micromolding, and 3D printing. In actual testing and applications, if the function of one electrode in the microneedle array is damaged, it may cause the entire microneedle array to fail or fail to realize all functions. This results in a low fault tolerance and lack of convenience when the microneedle array is used for detection. On the other hand, the integrated microneedle array design is also difficult to control the cost in large-scale batch production. In particular, photolithography technology involves complex, multi-step and expensive procedures, and the extremely high machine price of precision 3D printing has a great impact on the cost control of microneedle preparation. Although the method of preparing electrodes by micromolding casting is more suitable for large-scale production and cost reduction, the sensor resolution is often low and there are greater restrictions on materials.

[0064] The following describes in detail a method and system for preparing a pluggable microneedle electrode array according to an embodiment of the present invention with reference to the accompanying drawings. First, the method for preparing a pluggable microneedle electrode array according to an embodiment of the present invention will be described with reference to the accompanying drawings.

[0065] A method for preparing a pluggable microneedle electrode array is provided in an embodiment of the present invention. The method for preparing a pluggable microneedle electrode array in an embodiment of the present invention mainly comprises the following steps:

[0066] An array base plate is provided, on which a microneedle insertion hole is fixed; a detachable connection structure is installed inside the microneedle insertion hole;

[0067] Assembling a plurality of microneedle electrodes and a microconnector into a microneedle connector;

[0068] The microneedle connector is embedded in the microneedle socket through a detachable connection structure to form a pluggable microneedle electrode array with the array base plate.

[0069] In some possible implementations, reference Figure 1 The assembly relationship diagram of the micro-needle connector is shown. The socket is fixed to the base plate by soldering, and the micro-needle connector is connected by a detachable connection structure. The detachable connection structure can be a spring structure, a claw spring structure, or a magnetic attraction structure.

[0070] The microneedle electrodes in the embodiments of the present application can be made of stainless steel as the substrate. Figure 2 As shown, a noble metal layer can be modified on the surface of the stainless steel needle, that is, the microneedle electrode can be made based on stainless steel and noble metals, refer to Figure 3 The noble metal layer includes gold and platinum. Figure 4 As shown. The microneedle electrode and the microconnector are assembled into a microneedle connector, refer to Figure 5 As shown. After the microneedle surface is modified with a noble metal layer, Figure 6 The cross-sectional view of the microneedle insertion hole is shown in Figure 7 As shown, the microneedle connector shown in the above figure is assembled into an electrode array, such as Figure 8 As shown. Fig. 9 As shown, there are through holes on the top for fixing with the micro-needle plug hole. The structure after the bottom plate and the micro-needle plug hole are fixed, as shown in FIG. Fig.10 The microneedle connector is embedded in the microneedle socket through a detachable connection structure, and together with the array base plate, a pluggable microneedle electrode array is formed, as shown in FIG. Fig.11 At the same time, a shell can be mounted on the microneedle to adjust the exposed length of the microneedle tip, see Fig.12 As shown. The above are the components of the microneedle electrode array. Fig.13 In other embodiments, refer to Fig.14 The physical assembly diagram shown, Fig.15 The effect after installation of the shell is shown.

[0071] The present application aims to provide a pluggable microneedle electrode array device and its preparation method based on the functional modification and micromachining of stainless steel fine needles. Combining a convenient and stable pluggable design with electrochemical sensing technology satisfies the microneedle electrodes on a customizable sensing detection array. In some embodiments, the main materials of the microneedle electrodes are based on stainless steel, precious metals gold and platinum, and stainless steel gives the entire microneedle structure good mechanical properties. Continuing to modify gold and platinum on stainless steel can make the material biocompatible and stable. To realize the integration of microneedles into a microneedle array, it is necessary to design the interface between the microneedles and the array base plate. In this design, a pluggable interface design is adopted, which selects mutually matching micro-connectors and micro-jacks to achieve stable pluggable operation. In this design, the microneedles modified with the precious metal layer and the micro-connectors are assembled into a pluggable microneedle connector by solder paste welding, and then the complete functional modification is further achieved on the microneedles by technical means such as drawing or electroplating. The matching microneedle sockets are welded and fixed to the array base plate, and the microneedle sockets can fix the embedded pluggable microneedle connectors through the internal claw spring structure.

[0072] By 3D printing a customized shell, an insulating base for the microneedle array is realized. Firstly, the length of the microneedles can be customized by the thickness of the shell. Secondly, the insulating shell can isolate the skin surface from contact with the microconnector or microjack, preventing impedance changes from causing changes in signal acquisition.

[0073] The pluggable microneedle electrode array is designed to improve the functionality, flexibility and reliability of the device. This design can be flexibly integrated into a variety of platforms and systems, such as wearable devices and portable monitoring devices, broadening its application range. In resource-limited environments, such as remote medical points or field research stations, the use of pluggable microneedles can reduce the need to store spare parts, and only replaceable microneedles need to be stored. For non-professionals, the pluggable design simplifies the replacement process, reduces the difficulty of operation, and improves user-friendliness. In addition, the pluggable interface encourages innovation in microneedle materials and designs, because newly developed microneedles can be more easily integrated into existing substrate systems without the need to redesign the entire system. On the other hand, microneedle electrodes can be quickly replaced to adapt to different marker detection or application scenarios. In addition, the pluggable design helps to extend the service life of the microneedle array and reduce the generation of waste. In summary, the design of pluggable microneedle electrode array has significant advantages in improving device performance, reducing maintenance costs, enhancing user experience, and promoting technological innovation, making this technology have broad application prospects in multiple fields, especially in biomarker detection, precision medicine, and personalized diagnosis and treatment.

[0074] In short, this technical solution uses a low-cost commercial pluggable interface to prepare the sensor. If the connection interface between the microneedle and the array substrate is customized, it can ensure pluggability while achieving a smaller microneedle array distribution area, stable electrical connection and reliable plug-in replacement. The pluggable solution in this technical solution is based on mechanical fixation of the retaining spring in the socket. Mechanical fixation will cause mechanical deformation after long-term use, affecting the effect. Considering a customized magnetic suction structure will further increase the stability of the microneedle array.

[0075] Optionally, in one embodiment of the present invention, the method further comprises:

[0076] A custom shell was 3D printed, and the microneedle electrodes passed through the shell to contact the shell with the array base.

[0077] In some possible implementations, the array base plate and the microneedle insertion holes are fixed by soldering. The shell is used as an insulating base for the microneedle electrode array; the shell can achieve an insulating effect, and the thickness of the shell can be adjusted according to actual needs. The microneedle electrode can be a sensing electrode with a specific function to sense and detect various biochemical markers.

[0078] Optionally, in one embodiment of the present invention, the microneedle connector is prepared by the following steps:

[0079] The microneedle electrode is determined to have a stainless steel needle as the substrate, and the stainless steel microneedle electrode is treated by acid cleaning and oxidation film treatment and electroplating with precious metals to obtain a gold electrode;

[0080] The gold electrode is cut to obtain a size electrode; the size electrode is assembled with a micro connector through a detachable connection structure to obtain a microneedle connector.

[0081] Reference Fig.16 The preparation process of the microneedle electrode of one embodiment shown is from a stainless steel needle to a gold electrode; assembled into a microneedle joint, and then electroplated with a noble metal layer to obtain a counter electrode, and then through corresponding treatment, a metabolite working electrode is obtained. It can be understood that the microneedle can be based on a stainless steel needle with a diameter of 0.2 mm to enhance the mechanical strength of the electrode. Fig.17aAs shown in the figure, the stainless steel needle is electroplated with gold after the oxide film is cleaned with pickling solution to obtain a gold electrode. After the stainless steel needle is pickled with pickling solution, the gold plating effect can be optimized, so that it has a dense and uniform gold layer surface for easy modification. After the gold electrode is obtained by electroplating, the gold electrode is cut in batches to obtain gold electrodes with the same size accuracy. The cut stainless steel microneedle ends are welded and fixed with mini socket connectors by solder paste to form Au microneedle pin connectors, and then the microneedles with different functions are modified according to the requirements. The microneedle array substrate is designed by EDA. Due to the rapid development of printed circuit boards, the microneedle array substrate can be small, low-cost and mass-produced, and its electrical connection is stable and reliable. The microneedle array substrate vias and receptacle connectors are fixed by soldering to form a board receptacle. Thanks to the crown spring structure in the receptacle, the microneedle plug can be firmly fixed to the receptacle, and the microneedle plug can be safely and conveniently removed. After the functionally modified microneedle plug is combined with the hole seat, a dedicated plug-in microneedle array is formed. In specific applications, the plug-in design of the multi-parameter microneedle array only requires the replacement of microneedles with performance loss without replacing the entire array. Furthermore, the sensing electrodes of the multi-parameter microneedle sensor array prepared in this work can be adjusted as needed and replaced with a variety of functionalized microneedle sensing electrodes, in order to achieve the sensing detection of various biochemical markers, such as glucose, lactate, dopamine and various ions.

[0082] In some possible implementations, when preparing microneedle electrodes, the experimental materials that need to be prepared include the following:

[0083] Stainless steel needle (SS201, 0.20×40mm). Sodium gold sulfite solution (Yuncaitaotao Taobao Store). Platinum standard solution (Platinum standard solution, Yuncaitaotao Taobao Store). Stainless steel pickling solution (stainless-steel pickling solution). Uricase solution is used for functional modification of uric acid sensing electrode. When preparing uricase solution, 1wt% bovine serum albumin (BSA), 15mg / mL uricase oxidase (≥2 units / mg solid, from Candida) and 0.5wt% glutaraldehyde (20–25%) are mixed in sequence according to 5:1:2, and stirred evenly to make the uricase solution produce a gel-linked structure. If BSA and glutaraldehyde are mixed, the two will directly generate a gel-linked structure, which will reduce the gel-linked rate of uricase. Finally, uricase is modified on the surface of the metal electrode by immersing the electrode in the uricase solution. Polyaniline (PANI) is used for functional modification of pH electrode. The polyaniline solution was prepared by mixing 240 μL aniline, 0.54 mL 98% concentrated sulfuric acid, and 10 mL deionized water. The preparation of the reference electrode required PVB modification, and 791 mg PVB and 500 mg NaCl were diluted in 10 mL methanol to prepare the PVB solution. In the in vitro electrochemical characterization, uric acid (UA), sodium chloride (NaCl), potassium chloride (KCl), calcium chloride (CaCl2), magnesium chloride (MgCl2), glucose, etc. were all used in PBS buffer (pH = 7.2) as solvent. The pH sensing characterization solution was based on different ratios of 1 / 15 mol / L K2HPO4 and 1 / 15 mol / L NaH2PO4, and different pH solutions were prepared by pH meter. Unless otherwise stated, all chemicals were from Sigma-Aldrich and used as received. Unless otherwise stated, all solutions were prepared using PBS solution.

[0084] In some embodiments, Fig.17a The preparation process of the Au microneedle pin connectors shown is as follows:

[0085] The stainless steel needle was cut to leave the needle tip (about 3 cm long). The oxide layer on the needle surface was effectively removed by using a stainless-steel pickling solution. The treated stainless steel needle was fixed to the electrode holder of the working electrode to be immersed in the sodium gold sulfite solution. A commercial Ag / AgCl reference electrode and a gold sheet were selected as the counter electrode. An electrochemical workstation (CH Instruments) was used to electroplate for 500 s at a current of -2 mA according to the ISTEP method to form a stable gold layer on the needle surface. The board receptacle and mini socket connectors were purchased from the Taobao store of Shenzhen Shangyi Electronic Technology Company. The board receptacle model is a 0.9K crown spring adapter male needle sensor jack with a size of 2.5×2.0×5.2 mm. The mini socket connector model is YKZ-0515S-G with a size of 0.98×0.31×5.15 mm. The gold electrode was placed in the cutting through hole (16 mm high) to cut the microneedle electrode to a length of 1.6 cm. Then, solder paste was placed in the socket of the mini socket connector, and the gold electrode was placed in the mini socket connector. Finally, it was fixed by soldering with an electric soldering iron to ensure good conductivity, and the gold electrode microneedle pin connectors were prepared.

[0086] Optionally, in one embodiment of the present invention, the stainless steel microneedle electrode is subjected to an acid wash solution treatment for cleaning the oxide film and an electroplating treatment for a precious metal to obtain a gold electrode, comprising:

[0087] The oxide layer on the surface of the stainless steel microneedle electrode is removed by pickling solution, and the treated stainless steel microneedle electrode is fixed on the electrode clip of the working electrode and immersed in a sodium gold sulfite solution; the counter electrode is a Ag / AgCl reference electrode and a gold sheet;

[0088] According to the ISTEP method, electroplating is performed by a first current for a first time using an electrochemical workstation to form a stable gold layer on the surface of the stainless steel microneedle electrode to obtain a gold electrode; the first current is -1 to -4 mA, and the first time is 400 to 600 seconds.

[0089] Optionally, in one embodiment of the present invention, the gold electrode is cut to obtain a size electrode; the size electrode is assembled with a micro connector through a detachable connection structure to obtain a microneedle connector, comprising:

[0090] Put the gold electrode into the cutting through hole to cut the gold electrode to obtain a size electrode; the height of the cutting through hole is the length of the size electrode;

[0091] Solder paste is put into the hole of the micro connector, and then the size electrode is put into the micro connector, and a welding and fixing operation is performed to obtain a micro needle connector.

[0092] Optionally, in one embodiment of the present invention, the microneedle electrode comprises a H2O2 sensing electrode, and the H2O2 sensing electrode is prepared by the following steps:

[0093] The microneedle connector is fixed to the electrode holder of the working electrode and immersed in the platinum sulfite solution;

[0094] Electroplating is performed for a second period of time at a second current using an electrochemical workstation, and after electroplating, the electrode is cleaned using an ultrasonic cleaning device; the electrode cleaning time is 5 to 15 minutes; the second current is -200μA to -400μA, and the second period of time is 100 to 300s.

[0095] In some possible embodiments, in order to enhance the sensitivity of the sensing electrode, in a three-electrode system, a gold electrode microneedle pin connector based on a stainless steel needle is fixed to the electrode clip of the working electrode, immersed in a platinum sulfite solution (Cloudy Amoy), and then electroplated at -300μA for 200s through an electrochemical workstation, and after the electroplating is completed, the electrode is cleaned for 10 minutes using an ultrasonic cleaning device. The prepared Au / Pt electrode has sensing sensitivity to H2O2, and a H2O2 sensing electrode is obtained.

[0096] Optionally, in one embodiment of the present invention, referring to Fig.17b As shown, the microneedle electrode includes a sensing electrode, and the sensing electrode is prepared by the following steps:

[0097] The microneedle electrode part of the prepared microneedle connector is dipped in an oxidase solution and slowly dried overnight at room temperature to obtain a metabolite oxidase sensing electrode;

[0098] Alternatively, an ion selective membrane is modified on a microneedle electrode modified with a gold layer to obtain an ion sensing electrode.

[0099] Further, in one embodiment of the present invention, the microneedle electrode includes a reference electrode, and the reference electrode is prepared by the following steps:

[0100] The microneedle electrode modified with the gold layer is subjected to a pull coating process in an Ag / AgCl paste and placed in an oven for drying; the temperature of the oven is 70 to 90° C., and the drying time is 1.5 to 2.5 hours;

[0101] The prepared PVB solution is subjected to ultrasonic oscillation treatment, and the dried Ag / AgCl is placed in liquid PVB for stretch coating treatment, and then waits for drying to obtain a reference electrode.

[0102] In some embodiments, the preparation process of the counter electrode and the reference electrode is:

[0103] In this work, SS201 / Au / Pt electrode was used as the counter electrode. For the preparation of the reference electrode, Au microneedle pin connectors based on stainless steel needles were drawn and coated in Ag / AgCl paste (JY-20, DongFangJianCai), and then dried in an oven at 80°C for 2 hours. Subsequently, the prepared PVB solution was ultrasonically vibrated, and the dried Ag / AgCl was placed in liquid PVB for uniform drawing and coating, and then dried.

[0104] Further, in one embodiment of the present invention, the microneedle electrode includes a pH sensing electrode, and the pH sensing electrode is prepared by the following steps:

[0105] The gold-layered microneedle electrode was drawn and coated in a CNT solution and then immersed in a PANI solution;

[0106] The electrochemical workstation was used to perform electroplating using the CV method with 60 segments; the electroplating parameters were -0.1 to 0.8 V, and the scan rate was 0.02 to 0.08 V / s.

[0107] Based on the H2O2 sensing electrode, it can be further modified into a uric acid sensing electrode. For the uric acid sensing electrode, the Pt / Au electrode was dip-coated in a uricase solution and slowly dried overnight at room temperature to obtain a uric acid sensing electrode. For the pH sensing electrode, a gold electrode (Au electrode) based on a stainless steel needle was drawn in a CNT solution and then immersed in a PANI solution. The electrochemical workstation was electroplated using the CV method with 60 segments, the electroplating parameters were -0.1 to 0.8 V, and the scan rate was 0.05 V / s. All chemicals were from Sigma-Aldrich.

[0108] Furthermore, in one embodiment of the present invention, the method further comprises:

[0109] The microneedle array was determined to be arranged in a regular hexagonal shape, the number of microneedle electrodes was 7, and the center position was the reference electrode.

[0110] In some embodiments, the microneedle array is arranged in a regular hexagon, with a total of 7 microneedle electrodes to achieve high-precision sensing of three parameters. Specifically, the center of the regular hexagon is a PVB reference electrode. Three sensing electrodes (illustratively, can be used to detect uric acid, ROS and pH) and three short-circuited counter electrodes are evenly distributed in six corners, and the distance between each electrode is 3mm. The miniaturized design of the microneedle array enables it to be implanted in subcutaneous lesions according to the patient's specific condition, and UA, ROS and pH values ​​are detected in the interstitial fluid.

[0111] Reference Fig.18 As shown, each sensing electrode sample is fixed to the sample stage by conductive glue, and the surface morphology and microstructure of each sensing electrode of the multi-parameter microneedle array are observed by scanning electron microscopy (SUPRA 60, Zeiss). Among them, (a) SEM characterization of the electrode substrate SS201 stainless steel needle, (b) characterization of the stainless steel needle after gold electroplating. (c) The surface morphology after the gold layer is modified with a platinum layer, which can be used as a counter electrode and H2O2 electrode. (d) Characterization of uricase modified on the Pt layer. (e) Characterization of different layers of the pH electrode. The intermediate modification process is to draw CNT on the gold layer, and finally electroplating PANI on the CNT to achieve H+ selective membrane. (f) Electron microscopy characterization of different modified layers of the reference electrode. The intermediate modification process is to draw Ag / AgCl coating on the gold and dry it, and finally draw a layer of PVB on the Ag / AgCl coating to ensure the stability of Ag / AgCl.

[0112] Reference Fig.19As shown, an electrochemical workstation (CHI760E, CH Instruments) was used to perform electrochemical characterization on the three sensing electrodes, using commercial Ag / AgCl electrodes and platinum electrodes as reference electrodes and counter electrodes, respectively, to provide a stable evaluation of the working electrode. The selectivity of the electrochemical sensing electrodes for pH, ROS and uric acid was evaluated by adding a certain concentration of interfering substances to the solution in turn. For the pH sensing electrode, the electrochemical workstation characterized the open circuit potential of the two-electrode system (working electrode and reference electrode). The changes in the open circuit potential of the test substance at different concentrations were recorded. For the metabolite sensing electrode, a three-electrode system (working electrode, counter electrode and reference electrode) was used, in which the potentials applied to the two sensing electrodes (uric acid and H2O2) were 0.5V and -0.5V, respectively). In vitro performance characterization of the sensing electrode, the gradient changes in the detection of each parameter are indicated by arrows. Among them, (a) i-iv electrochemical detection performance of UA electrodes. The uric acid detection gradient is 0.1mM, ranging from 0.1mM to 1.0mM. The specificity of the UA sensing electrode was tested with MgCl2 (0.5mM), KCl (1mM), NaCl (1mM), Glucose (0.1mM), CaCl2 (0.5mM) and NaH2PO4 (0.1mM) as interfering substances. (b)i-iv are the electrochemical detection performance of the ROS electrode. The ROS detection gradient is 1.25mM, ranging from 1.25mM to 10.00mM. The specificity of the ROS sensing electrode was tested with Uric acid (0.4mM), CaCl2 (0.5mM) and NaH2PO4 (0.1mM) as interfering substances. (c)i-iv are the electrochemical detection performance of the pH electrode. The pH detection gradient is 0.5, and the pH value ranges from pH=6.0 to pH=8.0. The specificity of the pH sensing electrode was tested using NaCl (1 mM), Glucose (0.1 mM), CaCl2 (0.5 mM), Uric acid (0.4 mM) and KCl (1 mM) as interferents.

[0113] The following is a detailed introduction to the preparation method of the pluggable microneedle electrode array proposed in this application using a specific embodiment:

[0114] Based on functionalized microneedle electrodes, a pluggable microneedle electrode array was prepared, which can be integrated into a dedicated portable device to realize the collection and processing functions of the entire monitoring system. The number and shape of the microneedle array can be adjusted according to demand. In the example of the application of this technical solution, the microneedle array is designed to be arranged in a regular hexagon, with a total of 7 microneedle electrodes, which can achieve high-precision sensing of three different parameters. Specifically, the center of the regular hexagon is set as the reference electrode to ensure a closer distance to the working electrode. Three sensing electrodes and three short-circuited counter electrodes are evenly distributed in the six corners, and the distance between each electrode is 3mm. Miniaturized design of the microneedle array.

[0115] All microneedles are based on stainless steel needles with a diameter of 0.2 mm ( Figure 2 ) to enhance the mechanical strength of the electrode. The stainless steel needle is cleaned of the oxide film with pickling solution and then electroplated with gold to obtain a gold electrode ( Figure 3 ). After the stainless steel needle is pickled with pickling liquid, the gold plating effect can be optimized, so that it has a dense and uniform gold layer surface for easy modification. After the gold electrode is obtained by electroplating, the gold electrode is cut in batches to obtain gold electrodes with the same size accuracy. The claw spring structure inside the micro connector can initially fix the microneedle ( Figure 4 ), and then the cut stainless steel microneedle end is welded and fixed to the micro connector through solder paste to form a pluggable microneedle connector ( Figure 5 and Figure 6 ), and then modify the different functional microneedles according to needs.

[0116] The crown spring structure and aperture size inside the micro jack ( Figure 7 ), which enables stable and secure connection with micro connectors ( Figure 8 The microneedle array substrate is designed by EDA (Electronic Design Automation). Fig. 9 ). Due to the rapid development of printed circuit boards, microneedle array substrates can be small, low-cost and mass-produced, and their electrical connections are stable and reliable. The microneedle array base plate vias and micro-jacks are fixed by soldering ( Fig.10) to form a pluggable microneedle electrode array base. Thanks to the mechanical structure of the crown spring, the microneedle connector can be firmly and conveniently fixed and removed in the micro-jack. After the functionally modified microneedle connector is combined with the microneedle array base, a dedicated pluggable microneedle array is formed. In specific applications, the plug-in design only requires the replacement of microneedles with performance loss without replacing the entire array. In addition, the pluggable microneedle electrode array can achieve microneedles of different lengths by combining with insulating shells of different thicknesses for application in in vivo detection. Furthermore, the sensing electrodes of the multi-parameter microneedle sensor array prepared in this work can be adjusted as needed and replaced with a variety of functionalized microneedle sensing electrodes in order to realize the sensing detection of various biochemical markers, such as glucose, lactate, dopamine and various ions. The pluggable microneedle electrode array is miniaturized and low-cost, and can be functionally modified based on precious metal materials, bioproteases and ion-selective membranes to achieve tight electrical connection of the sensor and simple replaceable design.

[0117] Preparation process of pluggable microneedle connector: Cut the stainless steel needle and leave the needle tip (about 3 cm long). Use stainless steel pickling solution to effectively remove the oxide layer on the needle surface. Fix the treated stainless steel needle to the electrode clip of the working electrode to immerse it in sodium gold sulfite solution, and select commercial Ag / AgCl reference electrode and gold sheet as counter electrode. Use electrochemical workstation according to ISTEP method, generally use -1~-4mA current for electroplating for 400~600s to form a stable gold layer on the needle surface. In order to enhance the sensitivity of the sensing electrode, in the three-electrode system, the gold electrode microneedle connector with stainless steel needle as the substrate is fixed to the electrode clip of the working electrode, immersed in platinum sulfite solution, and then electroplated at -300μA for 200s through the electrochemical workstation. After the electroplating is completed, the electrode is cleaned with ultrasonic cleaning equipment for 10min. The micro connector and micro jack are purchased from the Taobao store of Shenzhen Shangyi Electronic Technology Co., Ltd. The micro-jack is a 0.9K crown spring adapter male needle sensor jack with a size of 2.5×2.0×5.2mm. The micro-connector model is YKZ-0515S-G, with a size of 0.98×0.31×5.15mm. The gold electrode is placed in the cut through hole (16mm high) to cut the micro-needle electrode to a length of 1.6cm. Then, solder paste is placed in the hole of the micro-connector, and the stainless steel electrode modified with a precious metal layer is placed in the micro-connector. Finally, it is soldered and fixed by an electric soldering iron to ensure its good conductivity and prepared as a pluggable micro-needle connector.

[0118] Preparation process of sensing electrode: Based on the above, the pluggable microneedle connector can be further modified into a sensing electrode with biological protease. For the sensing electrode modified with oxidase, the microneedle electrode part of the prepared pluggable microneedle connector is generally dipped in the oxidase solution and slowly dried overnight at room temperature to obtain the metabolite oxidase sensing electrode. For ion sensing electrodes, the ion selective membrane is often further modified on the microneedle electrode modified with the gold layer.

[0119] Preparation process of counter electrode and reference electrode: The design of the pluggable microneedle electrode array adopts the scheme of common reference electrode and counter electrode to improve the integration of the sensing end and hardware to realize the dynamic information collection of biomarkers. In this design, SS201 / Au / Pt electrode is used as the counter electrode. For the example preparation of the reference electrode, the microneedle electrode modified with the gold layer is drawn in the Ag / AgCl paste and then placed in an 80℃ oven for 2h. Subsequently, the prepared PVB solution is ultrasonically oscillated, and the dried Ag / AgCl is placed in the liquid PVB for uniform drawing and drying, and then it is ready.

[0120] Preparation and integration of pluggable microneedle electrodes: Fig.16 As shown, the oxidase modification is taken as an example. The integration of the pluggable microneedle electrode array is shown in Fig.13 As shown, the array base plate is fixed to the micro-jack by soldering, and then the prepared microneedle electrode is inserted into the micro-jack by tweezers and fixed. Finally, the insulating shell is assembled to obtain the pluggable microneedle electrode that can be used. Thanks to the maturity of PCB design and manufacturing technology, the miniaturized microneedle array can be flexibly worn on the body, achieving minimally invasive transdermal and ISF analysis.

[0121] Specific embodiment 1:

[0122] 1. In the specific example, this design can detect uric acid, reactive oxygen and pH value, and can connect the hardware circuit system to realize the dynamic collection of multiple physiological parameters. The real-time collected data can be transmitted to the mobile device via low-power Bluetooth and dynamically displayed in the custom-designed Android application.

[0123] 2. The preparation of the uric acid sensing electrode is to fix the gold electrode microneedle connector based on the stainless steel needle to the electrode clip of the working electrode in the three-electrode system, immerse it in a platinum sulfite solution, and then electroplate it at -300μA for 200s through an electrochemical workstation. After the electroplating is completed, the electrode is cleaned with an ultrasonic cleaning device for 10 minutes. After drying, the uricase solution is then applied and slowly dried overnight at room temperature to obtain a uric acid sensing electrode.

[0124] 3. The preparation of the active oxygen sensing electrode is to fix the gold electrode microneedle connector based on the stainless steel needle to the electrode clip of the working electrode in the three-electrode system, immerse it in a platinum sulfite solution, and then electroplate it at -300μA for 200s through an electrochemical workstation. After the electroplating is completed, the electrode is cleaned with an ultrasonic cleaning device for 10 minutes. After drying, the active oxygen sensing electrode is obtained.

[0125] The pH sensing electrode was prepared by drawing and coating the gold electrode with stainless steel needle as the substrate in the CNT solution, and then immersed in the PANI solution. The electrochemical workstation was electroplated by CV method with 60 segments, the electroplating parameters were -0.1 to 0.8V, and the scanning rate was 0.05V / s. After the electroplating was completed, it was dried to obtain the active oxygen sensing electrode.

[0126] In summary, the method for preparing a pluggable microneedle electrode array according to an embodiment of the present invention comprises: providing an array base plate, on which a microneedle socket is fixed; a detachable connection structure is installed inside the microneedle socket; assembling a plurality of microneedle electrodes and a microconnector into a microneedle connector; embedding the microneedle connector into the microneedle socket through the detachable connection structure, and forming a pluggable microneedle electrode array with the array base plate. The embodiment of the present application realizes the detachable installation of the microneedle electrode through the detachable connection structure, which is convenient for replacing the microneedle electrode during the detection process, and is conducive to improving convenience. At the same time, the embodiment of the present application prepares the microneedle array through a conventional preparation method, and the cost is controllable. Therefore, the preparation method provided in the embodiment of the present application is conducive to reducing costs and improving convenience.

[0127] On the other hand, an embodiment of the present invention provides a pluggable microneedle electrode array, which is prepared by the above-mentioned method for preparing a pluggable microneedle electrode array.

[0128] It should be noted that the embodiments of the present application can set different types of microneedles corresponding to different preparation processes according to the specific use of the microneedle array. The present application does not limit the specific type and preparation process of each microneedle.

[0129] It can be seen that the contents of the above method embodiments are all applicable to the pluggable microneedle electrode array embodiment. The functions specifically implemented by the pluggable microneedle electrode array embodiment are the same as those of the above method embodiments, and the beneficial effects achieved are also the same as those achieved by the above method embodiments.

[0130] On the other hand, an embodiment of the present invention provides a detection device, including the above-mentioned pluggable microneedle electrode array.

[0131] Similarly, the contents of the above method embodiments are all applicable to the present device embodiments. The functions specifically implemented by the present device embodiments are the same as those of the above method embodiments, and the beneficial effects achieved are also the same as those achieved by the above method embodiments.

[0132] In some selectable embodiments, the function / operation mentioned in the block diagram may not occur in the order mentioned in the operation diagram. For example, depending on the function / operation involved, the two boxes shown in succession can actually be executed substantially simultaneously or the boxes can sometimes be executed in reverse order. In addition, the embodiment presented and described in the flow chart of the present invention is provided by way of example, for the purpose of providing a more comprehensive understanding of technology. The disclosed method is not limited to the operation and logic flow presented herein. Selectable embodiments are expected, wherein the order of various operations is changed and the sub-operation of a part for which is described as a larger operation is performed independently.

[0133] In addition, although the present invention is described in the context of functional modules, it should be understood that, unless otherwise specified, one or more of the functions and / or features can be integrated into a single physical device and / or software module, or one or more functions and / or features can be implemented in a separate physical device or software module. It is also understood that a detailed discussion of the actual implementation of each module is unnecessary for understanding the present invention. More specifically, in view of the properties, functions and internal relationships of the various functional modules in the device disclosed herein, the actual implementation of the module will be understood within the conventional skills of the engineer. Therefore, those skilled in the art can implement the present invention set forth in the claims without excessive experimentation using ordinary techniques. It is also understood that the specific concepts disclosed are merely illustrative and are not intended to limit the scope of the present invention, which is determined by the full scope of the appended claims and their equivalents.

[0134] If the functions are implemented in the form of software functional units and sold or used as independent products, they can be stored in a computer-readable storage medium. Based on this understanding, the technical solution of the present invention, or the part that contributes to the prior art or the part of the technical solution, can be embodied in the form of a software product. The computer software product is stored in a storage medium, including several programs to enable a computer device (which can be a personal computer, a server, or a network device, etc.) to perform all or part of the steps of the methods described in each embodiment of the present invention. The aforementioned storage medium includes: U disk, mobile hard disk, read-only memory (ROM, Read-Only Memory), random access memory (RAM, Random Access Memory), disk or optical disk, etc., which can store program codes.

[0135] The logic and / or steps represented in the flowchart or otherwise described herein, for example, may be considered as an ordered list of executable programs for implementing the logical functions, and may be embodied in any computer-readable medium for use by a program execution system, device or apparatus (such as a computer-based system, a system including a processor, or other system that can fetch and execute a program from a program execution system, device or apparatus), or in conjunction with such program execution systems, devices or apparatuses. For purposes of this specification, a "computer-readable medium" may be any device that can contain, store, communicate, propagate or transmit a program for use by a program execution system, device or apparatus, or in conjunction with such program execution systems, devices or apparatuses.

[0136] More specific examples of computer-readable media (a non-exhaustive list) include the following: an electrical connection with one or more wires (electronic device), a portable computer disk case (magnetic device), a random access memory (RAM), a read-only memory (ROM), an erasable and programmable read-only memory (EPROM or flash memory), an optical fiber device, and a portable compact disk read-only memory (CDROM). In addition, the computer-readable medium may even be a paper or other suitable medium on which the program is printed, since the program may be obtained electronically, for example, by optically scanning the paper or other medium, followed by editing, deciphering or, if necessary, processing in another suitable manner, and then stored in a computer memory.

[0137] It should be understood that the various parts of the present invention can be implemented by hardware, software, firmware or a combination thereof. In the above-mentioned embodiments, a plurality of steps or methods can be implemented by software or firmware stored in a memory and executed by a suitable program execution system. For example, if implemented by hardware, as in another embodiment, it can be implemented by any one of the following technologies known in the art or their combination: a discrete logic circuit having a logic gate circuit for implementing a logic function for a data signal, a dedicated integrated circuit having a suitable combination of logic gate circuits, a programmable gate array (PGA), a field programmable gate array (FPGA), etc.

[0138] In the above description of this specification, the description with reference to the terms "one embodiment / example", "another embodiment / example" or "certain embodiments / examples" etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representation of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described may be combined in any one or more embodiments or examples in a suitable manner.

[0139] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the claims and their equivalents.

[0140] The above is a specific description of the preferred implementation of the present invention, but the present invention is not limited to the embodiments. Those skilled in the art may make various equivalent modifications or substitutions without violating the spirit of the present invention. These equivalent modifications or substitutions are all included in the scope defined by the claims of the present invention.

Claims

1. A method for preparing a pluggable microneedle electrode array, characterized in that: The following steps are involved: Providing an array bottom plate, on which a microneedle insertion hole is fixed; a detachable connection structure is installed inside the microneedle insertion hole; Assembling a plurality of microneedle electrodes and a microconnector into a microneedle connector; The microneedle connector is embedded into the microneedle insertion hole through the detachable connection structure to form a pluggable microneedle electrode array with the array bottom plate.

2. The method for preparing a pluggable microneedle electrode array according to claim 1, characterized in that: The method further comprises: A shell is customized by 3D printing, and the microneedle electrode passes through the shell to contact the shell with the array bottom plate.

3. The method for preparing a pluggable microneedle electrode array according to claim 2, characterized in that: The microneedle connector is prepared by the following steps: Determining that the microneedle electrode is based on a stainless steel needle, performing an acid wash to clean the oxide film of the stainless steel microneedle electrode and electroplating a precious metal to obtain a gold electrode; Cutting the gold electrode to obtain a size electrode; The size electrode is assembled with the micro connector via a detachable connection structure to obtain a microneedle connector.

4. The method for preparing a pluggable microneedle electrode array according to claim 3, characterized in that: The step of washing the stainless steel microneedle electrode with an acid wash solution to clean the oxide film and electroplating the stainless steel microneedle electrode with a precious metal to obtain a gold electrode comprises: The oxide layer on the surface of the stainless steel microneedle electrode is removed by pickling solution, the treated stainless steel microneedle electrode is fixed on the electrode clip of the working electrode, and immersed in a sodium gold sulfite solution; the counter electrode is a Ag / AgCl reference electrode and a gold sheet; According to the ISTEP method, electroplating is performed by a first current for a first time using an electrochemical workstation to form a stable gold layer on the surface of the stainless steel microneedle electrode to obtain a gold electrode; the first current is -1 to -4 mA, and the first time is 400 to 600 seconds.

5. The method for preparing a pluggable microneedle electrode array according to claim 3, characterized in that: The gold electrode is cut to obtain a size electrode; The size electrode is assembled with the micro connector via a detachable connection structure to obtain a microneedle connector, comprising: Putting the gold electrode into the cutting through hole to cut the gold electrode to obtain a size electrode; the height of the cutting through hole is the length of the size electrode; Solder paste is put into the hole of the micro joint, and then the size electrode is put into the micro joint, and a welding and fixing operation is performed to obtain a micro needle joint.

6. The method for preparing a pluggable microneedle electrode array according to claim 1, characterized in that: The microneedle electrode comprises a H2O2 sensing electrode, and the H2O2 sensing electrode is prepared by the following steps: Fixing the microneedle connector to the electrode holder of the working electrode and immersing it in a platinum sulfite solution; Electroplating is performed for a second period of time at a second current using an electrochemical workstation, and after electroplating, the electrode is cleaned using an ultrasonic cleaning device; the electrode cleaning time is 5 to 15 minutes; the second current is -200μA to -400μA, and the second period of time is 100 to 300s.

7. The method for preparing a pluggable microneedle electrode array according to claim 1, characterized in that: The microneedle electrode includes a sensing electrode, and the sensing electrode is prepared by the following steps: The microneedle electrode part of the prepared microneedle connector is dipped in an oxidase solution and slowly dried overnight at room temperature to obtain a metabolite oxidase sensing electrode; Alternatively, an ion selective membrane is modified on a microneedle electrode modified with a gold layer to obtain an ion sensing electrode.

8. The method for preparing a pluggable microneedle electrode array according to claim 1, characterized in that: The microneedle electrode includes a reference electrode, and the reference electrode is prepared by the following steps: The microneedle electrode modified with the gold layer is subjected to a pull coating process in an Ag / AgCl paste and placed in an oven for drying; the temperature of the oven is 70 to 90° C., and the drying time is 1.5 to 2.5 hours; The prepared PVB solution is subjected to ultrasonic oscillation treatment, and the dried Ag / AgCl is placed in liquid PVB for stretch coating treatment, and then waits for drying to obtain a reference electrode.

9. The method for preparing a pluggable microneedle electrode array according to claim 1, characterized in that: The microneedle electrode comprises a pH sensing electrode, and the pH sensing electrode is prepared by the following steps: The gold-layered microneedle electrode was drawn and coated in a CNT solution and then immersed in a PANI solution; Electroplating was performed using an electrochemical workstation with CV method set to 60 segments; Plating parameters - 0.1 to 0.8 V, scan rate 0.02 to 0.08 V / s.

10. The method for preparing a pluggable microneedle electrode array according to claim 1, characterized in that: The method further includes: determining that the microneedle array is arranged in a regular hexagon, the number of the microneedle electrodes is 7, and the center position is a reference electrode.

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