Flexible implantable biosensor and manufacturing method thereof

Abstract

The invention relates to the technical field of biosensor manufacturing, in particular to a flexible implantable biosensor and a manufacturing method thereof.The flexible implantable biosensor is characterized in that a reference electrode film, a working electrode film and a counter electrode film are stacked together to form a soft needle stacked body, and the reference electrode film comprises a first flexible substrate and a reference electrode layer; the working electrode thin film comprises a second flexible substrate and a working electrode layer, the counter electrode thin film comprises a third flexible substrate and a counter electrode layer, each layer of electrode is provided with a corresponding wire circuit and electrode arrangement, and the manufacturing method of the sensor comprises the steps of thin film preparation, hot pressing overlapping, pattern cutting and the like. Through the reasonable electrode layout and manufacturing process, the sensor is convenient to install and use, meanwhile, the laser tolerance of the working electrode is improved, the needed electrode can be accurately exposed out of the needle contact area, the active material can be formed on the surface of the electrode, the protective coating can be coated on the surface of the electrode, and the performance and stability of the sensor are guaranteed.

Description

Technical Field

[0001] The present application relates to the technical field of biosensor manufacturing, and in particular to a flexible implantable biosensor and a manufacturing method thereof. Background Art

[0002] With the advancement of healthcare and sensor technology, implantable flexible biosensors, such as continuous glucose monitoring, have become a major research focus for clinical applications such as diabetes management. These sensors play a vital role in accurately acquiring real-time physiological information from the human body, providing strong support for disease diagnosis, treatment, and prevention. They can help doctors adjust treatment plans promptly and improve patients' quality of life. Furthermore, with increasing awareness of health, market demand for these sensors is also growing, driving the continuous advancement of related technologies. An increasing number of research institutions and companies are investing in R&D in this field, striving to develop sensor products with improved performance and lower costs.

[0003] Currently, multi-layer screen printing is widely used in the manufacture of flexible implantable biosensors (such as continuous glucose monitoring devices). This technique involves sequentially stacking functional layers, such as electrodes, conductive wires, and insulating layers, onto a flexible substrate (e.g., PET or PI). For example, as described in the Chinese patent (Title: Implantable Biosensor and Preparation Method, Publication Number: CN114224334A), the process involves screen-printing a first layer of conductive paste onto the substrate and curing it. Next, an insulating material is applied locally or throughout the substrate to form a barrier layer. A second layer of conductive or sensitive material is then printed, and this process is repeated multiple times until the entire electrode structure is complete. To ensure insulation between the functional layers, the insulating ink or resin is typically cured by UV curing or drying after each printed layer. This method is relatively mature for mass production, but the process involves multiple operations, including stacking, screen replacement, curing, and insulation, making the production process quite complex.

[0004] Traditional multi-layer screen printing processes present numerous challenges. They are complex, requiring multiple precise alignments and rigorous control of each screen printing layer. This places extremely high demands on both the operator's skill level and the equipment's precision. Furthermore, the process is cumbersome, requiring multiple layers to be printed sequentially and combined with processes such as local baking or UV curing. This not only complicates the process but also leads to relatively long production cycles and increased costs. Furthermore, the curing conditions of different inks (conductive and insulating layers) vary significantly, affecting the interlayer bond strength. Furthermore, improper alignment and process control can easily lead to defects such as disconnections, short circuits, and interlayer defects between layers. Summary of the Invention

[0005] In order to overcome the shortcomings of the above-mentioned existing technologies, the present application provides a method for manufacturing a flexible implantable biosensor, which can simplify the process flow, reduce the process difficulty, shorten the production cycle, and the resulting sensor is not prone to defects such as broken wires, short circuits or poor interlayer properties, thereby realizing the independent manufacturing and efficient integration of multi-electrode soft needle systems while ensuring biocompatibility and long-term stability.

[0006] This application is achieved through the following technical solutions: A flexible implantable biosensor comprising: A reference electrode film comprising a first flexible substrate and an independent reference electrode layer formed on the first flexible substrate, the reference electrode layer comprising a first wire circuit and a reference electrode connected to the first wire circuit and disposed in the needle contact area; A working electrode film comprising a second flexible substrate and a composite working electrode layer formed on the second flexible substrate, wherein the working electrode layer comprises a second wire circuit and a working electrode connected to the second wire circuit and disposed in the needle contact area; a counter electrode film, comprising a third flexible substrate and a counter electrode layer formed on the third flexible substrate, wherein the counter electrode layer comprises a counter electrode; Among them, the reference electrode film, the working electrode film and the counter electrode film are combined together by hot pressing and laminating and formed into a soft needle laminate, and the soft needle laminate has a needle contact area and an installation area. The second flexible substrate and the first flexible substrate have different lengths in the needle contact area, so that the needle contact area of the soft needle laminate reveals the working electrode and the reference electrode.

[0007] By adopting the above technical solution, compared with the existing multi-layer screen printing lamination process, this flexible implantable biosensor laminates the reference electrode film, working electrode film, and counter electrode film together, breaking through the traditional single-substrate limitation and enabling the independent manufacture of the reference electrode, working electrode, and counter electrode modules. This avoids the cumbersome processes of sequential multi-layer printing and localized baking or UV curing, solving the problems of the traditional process with cumbersome steps and long production cycles, and shortening the production cycle. At the same time, each film independently prepares the reference electrode layer, working electrode layer, and counter electrode layer, eliminating the need for direct lamination and printing. This reduces the difficulty of alignment and the problems of broken wires, short circuits, or interlayer defects caused by improper alignment or process control, reducing the risk of short circuits. In addition, the needle contact area of the soft needle laminate can expose the working electrode and reference electrode in a stepped manner, compensating for the difference in flexibility with axial pressure, and facilitating the sensor's detection of target analytes.

[0008] Optionally, the reference electrode layer, the working electrode layer and the counter electrode layer are stacked in sequence in the vertical direction and remain independent of each other, and the soft needle stack is provided with positioning holes in the installation area that penetrate the reference electrode film, the working electrode film and the counter electrode film.

[0009] By adopting the above technical solution, the reference electrode layer, the working electrode layer and the counter electrode layer are stacked in sequence in the vertical direction and remain independent of each other, which can avoid problems such as broken wires, short circuits or interlayer defects caused by improper interlayer alignment or process control in traditional multi-layer screen printing processes, reduce interference and short circuit risks between multiple layers, and improve the safety and reliability of the sensor; at the same time, the soft needle laminate is provided with positioning holes that pass through the reference electrode film, the working electrode film and the counter electrode film in the installation area, which facilitates the positioning and installation of the sensor during subsequent use, simplifies the assembly process, and improves production efficiency.

[0010] Optionally, the working electrode layer is located between the reference electrode and the counter electrode layer, and the working electrode film and the reference electrode film are positively stacked, so that the working electrode layer and the reference electrode layer are arranged in the same direction, and the counter electrode film and the working electrode film are reversely stacked, so that the counter electrode layer and the working electrode layer are arranged back to back, so that the needle contact area of the soft needle stack reveals the working electrode, the reference electrode and the counter electrode on the front and the back.

[0011] By adopting the above technical solution, the working electrode layer is located between the reference electrode and the counter electrode layer, and the working electrode layer and the reference electrode layer are arranged in the same direction, and the counter electrode layer and the working electrode layer are arranged back to back, so that the needle contact area of the soft needle laminate can reasonably distribute electrodes on both the front and back sides, thereby optimizing space utilization; and this layout method helps to identify the positions of each electrode more clearly and quickly during the assembly process, thereby improving assembly efficiency. At the same time, the needle contact area of the soft needle laminate can reveal the working electrode, reference electrode on the front and the counter electrode on the back, which is convenient for subsequent connection with the external circuit to realize the sensor function.

[0012] Optionally, the counter electrode film, the working electrode film and the reference electrode film are arranged in the same direction, and the third flexible substrate, the second flexible substrate and the first flexible substrate have different lengths in the needle contact area, so that the needle contact area of the soft needle stack exposes the counter electrode, the working electrode and the reference electrode in a step-by-step manner starting from the needle tip.

[0013] By adopting the above technical solution, the counter electrode film, the working electrode film and the reference electrode film are arranged in the same direction, and the third flexible substrate, the second flexible substrate and the first flexible substrate have different lengths in the needle contact area, so that the needle contact area of the soft needle laminate reveals the counter electrode, the working electrode and the reference electrode in sequence starting from the needle tip. This layout is conducive to the contact between the electrodes of the sensor and external substances, better exerting the detection function, and facilitating the electrodes to collect and transmit signals, effectively improving the detection performance of the sensor.

[0014] Optionally, the installation area of the soft needle stack has a bending portion, and the first wire circuit, the second wire circuit and the counter electrode are staggered at the bending portion, so that the installation area of the soft needle stack exposes the external connection ends of the first wire circuit, the second wire circuit and the counter electrode.

[0015] By adopting the above technical solution, a bending portion is provided in the installation area of the soft needle laminate and the three wire lines are staggered in the bending portion, so that the external connection ends of the three wire lines are exposed in the installation area, which is convenient for connection with external equipment and is beneficial to the use of the sensor and signal transmission.

[0016] Optionally, the needle contact area and the installation area are integrally connected and formed in the same laser cutting area.

[0017] By adopting the above technical solution, the needle contact area and the installation area can be formed simultaneously by one laser cutting, which simplifies the production process and improves production efficiency.

[0018] A method for manufacturing a flexible implantable biosensor comprises the following steps: S1. Prepare a reference electrode film, and form a reference electrode layer on a first flexible substrate by a printing process, wherein the reference electrode layer includes a first wire circuit and a reference electrode connected to the first wire circuit and disposed in a needle contact area; S2. preparing a working electrode film, and forming a working electrode layer on a second flexible substrate by a printing process, wherein the working electrode layer includes a second wire circuit and a working electrode connected to the second wire circuit and disposed in the needle contact area; S3, preparing a counter electrode thin film, and forming a counter electrode layer on the third flexible substrate by a printing process, wherein the counter electrode layer includes a counter electrode; S4, laminating the reference electrode film, the working electrode film and the counter electrode film together through a hot pressing process; S5. Use laser engraving technology to perform graphic cutting on the stacked body of step S4 to form a soft needle stacked body, wherein the soft needle stacked body has a needle contact area and an installation area, and the second flexible substrate and the first flexible substrate have different lengths in the needle contact area, so that the needle contact area of the soft needle stacked body reveals the working electrode and the reference electrode.

[0019] By adopting the above technical solution, the reference electrode layer, working electrode layer and counter electrode layer are printed separately on different flexible substrates, then laminated by hot pressing process, and finally formed by laser engraving, which greatly reduces the alignment requirements and error rate of the lamination process, shortens the production cycle, and improves the yield rate; each layer has been dried and cured before lamination, and is finally firmly bonded by hot pressing, which significantly reduces the problems of short circuit and leakage between layers; the multi-layer flexible substrate structure ensures the flexibility, stability and mass production feasibility of the sensor; laser engraving can accurately remove excess parts, so that the working electrode and reference electrode are exposed in the needle contact area, which facilitates the detection of target analytes, and can also flexibly cut the shape of the sensor to facilitate miniaturization and diversified design.

[0020] Optionally, in the hot pressing process of step S4, the hot pressing temperature is 80-120°C, the pressure is 0.2-0.5 MPa, the hot pressing time is 30-60 seconds, and the air between the functional layers is removed by vacuum.

[0021] By adopting the above technical solution, the reference electrode film, working electrode film, and counter electrode film are hot pressed under the conditions of a hot pressing temperature of 80-120°C, a pressure of 0.2-0.5MPa, and a hot pressing time of 30-60 seconds. This precise parameter setting can achieve effective superposition of the reference electrode film, working electrode film, and counter electrode film under conditions of lower temperature, appropriate pressure, and time, reducing the damage to the performance of the film material caused by high temperature and high pressure, and reducing the technical difficulty of the hot pressing process. It does not require excessively high temperature and pressure, and reduces the requirements for equipment. At the same time, the air between the functional layers is removed by vacuum, avoiding problems such as uneven hot pressing due to residual air, reducing the risk of defects such as bubbles and delamination during the hot pressing process, and effectively solving the problem of difficulty in completely exhausting air in conventional hot pressing processes. This allows the functional layers to fit better and improves the quality and performance of the soft needle laminate.

[0022] Optionally, the reference electrode film, the working electrode film and the electrode film are respectively aligned using separate positioning holes or edge marks during the printing process; and the reference electrode film is pre-laser engraving technology to form a hollow area on the first flexible substrate before the printing process, so that the needle contact area of the soft needle stack in step S4 reveals the working electrode in advance.

[0023] By adopting the above technical solution, the use of separate positioning holes or edge marks for alignment can ensure that the reference electrode film, working electrode film and electrode film are accurately aligned during the printing process; before the printing process of the reference electrode film, the pre-laser engraving technology is used to form a hollow area on the first flexible substrate, which can make the needle contact area of the soft needle laminate reveal the working electrode in advance, prepare for subsequent processes, and simplify the production process.

[0024] Optionally, in step S2, the material used for the working electrode is graphene and one or more of carbon, platinum carbon or carbon nanotubes, which are prepared into a composite material by chemical blending or physical mixing to enhance the laser tolerance of the working electrode, so that the needle contact area of the soft needle laminate in step S5 can be removed by laser engraving technology to remove the first flexible substrate superimposed on the working electrode to reveal the working electrode; the electrode surfaces of the reference electrode and the working electrode are formed into an electrochemically active layer by deposition or attachment, and a biocompatible protective layer is coated on the non-electrode surface of the sensor; step S4 includes a UV pre-curing process before the hot pressing process; the laser engraving technology of step S5 includes wavelength switching technology.

[0025] By adopting the above technical solution, graphene is selected as the working electrode material by chemically blending or physically mixing one or more materials such as carbon, platinum carbon or carbon nanotubes to form a composite material, which enhances the laser tolerance of the working electrode, so that in step S5, the first flexible substrate superimposed on the working electrode can be removed by laser engraving technology to reveal the working electrode, and no reference electrode film is required. Before the printing process, a hollow area is formed on the first flexible substrate by pre-laser engraving technology, so that the needle contact area of the soft needle laminate in step S4 reveals the working electrode in advance, which greatly simplifies the process flow and improves production efficiency. In particular, graphene and carbon are mixed in a ratio of 1:2 to 1:5, or with platinum carbon in a ratio of 1:2 to 1:5. A composite material is prepared by chemical blending or physical mixing in a ratio of 1:1 to 1:3, or with carbon nanotubes in a ratio of 1:3 to 1:6, for use in a working electrode, which can effectively enhance the laser tolerance of the working electrode; an electrochemically active layer is formed on the electrode surfaces of the reference electrode and the working electrode to detect the target analyte, and a biocompatible protective layer is coated on the non-electrode surface of the sensor to improve the biocompatibility of the sensor and ensure the safety of implantation; adding a UV pre-curing process before the hot pressing process helps to improve the initial bonding strength and stability between the films, and the wavelength switching technology allows the laser engraving to flexibly adjust the wavelength according to the characteristics of different materials, thereby improving the cutting accuracy and efficiency and ensuring the forming quality of the soft needle laminate.

[0026] In summary, this application includes at least one of the following beneficial technical effects: 1. This application forms a soft needle laminate by laminating a reference electrode film, a working electrode film, and a counter electrode film, and each functional layer is printed on an independent flexible substrate, which greatly reduces the alignment requirements and error rate of the lamination process; 2. This application uses a printing process to prepare each electrode film, eliminating the need for multiple printing and insulation isolation on the same substrate, shortening the production cycle and improving the yield rate; 3. This application uses a hot pressing process to laminate the electrode films, and each layer is dried and cured before lamination, which significantly reduces the problems of short circuits and leakage between layers; 4. This application uses laser engraving technology to perform graphic cutting on the laminate, which can accurately remove excess parts and accurately define the integrated contour boundary of the needle contact area and the installation area. It has a more flexible miniaturized and diversified design. The flexible implantable biosensor produced is particularly suitable for dynamic blood glucose monitoring systems. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 1 is a schematic diagram of the front structure of the flexible implantable biosensor described in Example 1; Figure 2 1 is a schematic diagram of the back structure of the flexible implantable biosensor described in Example 1; Figure 3 is a schematic cross-sectional structural diagram of the flexible implantable biosensor described in Example 1; Figure 4 1 is a schematic diagram of the front structure of the flexible implantable biosensor described in Example 2; Figure 5 is a schematic cross-sectional view of the flexible implantable biosensor described in Example 2; Figure 6 Schematic diagram of the arrangement structure of the first flexible substrate and the reference electrode layer when preparing the reference electrode film in Example 3; Figure 7 This is a schematic diagram of the arrangement structure of the first flexible substrate and the reference electrode layer when preparing the working electrode film in Example 3; Figure 8 This is a schematic diagram of the arrangement structure of the first flexible substrate and the reference electrode layer when preparing the counter electrode film in Example 3; Figure 9 Schematic diagram of the relationship between the overlapping positions of the reference electrode film, the working electrode film, and the counter electrode film during the hot pressing process in Example 3; Figure 10 This is a schematic structural diagram of the laminated body in Example 4 formed into a soft needle laminated body using laser engraving technology; Figure 11 Schematic diagram of the relationship between the overlapping positions of the reference electrode film, the working electrode film, and the counter electrode film during the hot pressing process in Example 4; Figure 12 It is a schematic diagram of the arrangement structure of the electrochemical active layer and the biocompatible protective layer described in Example 5.

[0028] In the figure: 10, reference electrode film; 11, first flexible substrate; 12, reference electrode layer; 12a, first wire line; 12b, reference electrode; 13, hollow area; 20, working electrode film; 21, second flexible substrate; 22, working electrode layer; 22a, second wire line; 22b, working electrode; 30, counter electrode film; 31, third flexible substrate; 32, counter electrode; 4, needle contact area; 5, installation area; 51, bending part; 6, positioning hole; 7, edge mark; 8, electrochemical active layer; 9, biocompatible protective layer. DETAILED DESCRIPTION

[0029] The following will clearly and completely describe the technical solutions of the various embodiments of the present application in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present application, not all of the embodiments. Based on the embodiments of the present application, all other embodiments obtained by ordinary technicians in this field without making any creative work are within the scope of protection of this application.

[0030] Example 1 Reference Figures 1 to 3 The present invention discloses a flexible implantable biosensor, comprising: The reference electrode film 10 includes a first flexible substrate 11 and an independent reference electrode layer 12 formed on the first flexible substrate 11. The reference electrode layer 12 includes a first wire line 12a and a reference electrode 12b connected to the first wire line 12a and disposed in the needle contact area 4. The working electrode film 20 includes a second flexible substrate 21 and a composite working electrode layer 22 formed on the second flexible substrate 21. The working electrode layer 22 includes a second conductive line 22a and a working electrode 22b connected to the second conductive line 22a and disposed in the needle contact area 4. The counter electrode film 30 includes a third flexible substrate 31 and a counter electrode layer formed on the third flexible substrate 31 , wherein the counter electrode layer includes a counter electrode 32 ; Among them, reference Figures 1 to 3 The reference electrode film 10, the working electrode film 20 and the counter electrode film 30 are combined together by hot pressing and laminating to form a soft needle laminate. The soft needle laminate has a needle contact area 4 and an installation area 5. The needle contact area 4 and the installation area 5 are integrally connected and formed in the same laser cutting area; the second flexible substrate 21 and the first flexible substrate 11 have different lengths in the needle contact area 4, so that the needle contact area 4 of the soft needle laminate reveals the working electrode 22b and the reference electrode 12b.

[0031] Specifically, refer to Figures 1 to 3 The first flexible substrate 11, the second flexible substrate 21 and the third flexible substrate 31 can preferably be made of PET material with a thickness of 0.038 mm ± 0.005 mm. PET has good flexibility and chemical stability and can also be replaced by other flexible materials such as PI.

[0032] Reference Figures 1 to 3 The reference electrode film 10 includes a first flexible substrate 11 and a reference electrode layer 12 formed on the first flexible substrate 11, wherein the reference electrode layer 12 includes a first wire line 12a and a reference electrode 12b connected to the first wire line 12a and configured in the needle contact area 4; the first wire line 12a is used to transmit the signal of the reference electrode 12b, and can be produced by a printing process, such as screen printing or inkjet printing; the reference electrode 12b is generally made of silver, silver chloride, or a mixture of silver and silver chloride, etc. These materials have stable chemical properties and can provide a stable reference potential; the reference electrode 12b is connected to the first wire line 12a by conductive ink, etc. The conductive ink has good conductivity and adhesion, which can ensure a stable connection between the two.

[0033] Reference Figures 1 to 3 The working electrode film 20 includes a second flexible substrate 21 and a working electrode layer 22 formed on the second flexible substrate 21; the working electrode layer 22 includes a second wire line 22a and a working electrode 22b connected to the second wire line 22a and arranged in the needle contact area 4; the function of the second wire line 22a is to transmit the signal of the working electrode 22b, and the manufacturing method is similar to that of the first wire line 12a; the material used for the working electrode 22b can be one or more of carbon, platinum carbon or carbon nanotubes, and can also be prepared into a composite material by chemical blending or physical mixing with graphene. This composite material can enhance the laser tolerance of the working electrode 22b.

[0034] Reference Figures 1 to 3 The counter electrode film 30 includes a third flexible substrate 31 and a counter electrode layer formed on the third flexible substrate 31; the counter electrode layer includes a counter electrode 32, and the counter electrode 32 is generally made of carbon material or silver material, and no special sensitive material part needs to be printed.

[0035] Among them, reference Figures 1 to 3 The reference electrode layer 12, the working electrode layer 22 and the counter electrode layer are stacked in sequence in the vertical direction and remain independent of each other, so as to avoid mutual interference between the electrodes; and the soft needle laminate body is provided with a positioning hole 6 that penetrates the reference electrode film 10, the working electrode film 20 and the counter electrode film 30 in the installation area 5. The positioning hole 6 facilitates the installation and fixation of the sensor.

[0036] Reference Figures 1 to 3The working electrode layer 22 is located between the reference electrode 12b and the counter electrode layer, and the working electrode layer 22 and the reference electrode layer 12 are arranged in the same direction, and the counter electrode layer and the working electrode layer 22 are arranged back to back, so that the needle contact area 4 of the soft needle laminate body exposes the working electrode 22b and the reference electrode 12b on the front and the counter electrode 32 on the back. This arrangement allows the electrodes to better play their respective roles and improve detection efficiency.

[0037] Reference Figures 1 to 3 The installation area 5 of the soft needle laminate has a bending portion 51, and the first wire line 12a, the second wire line 22a and the counter electrode 32 are staggered at the bending portion 51, so that the installation area 5 of the soft needle laminate exposes the external connection ends of the first wire line 12a, the second wire line 22a and the counter electrode 32, which are convenient for connection with external equipment to realize signal transmission.

[0038] The implementation principle of this embodiment is: by stacking the reference electrode film 10, the working electrode film 20 and the counter electrode film 30 to form a soft needle laminate, each electrode layer is independently set, which effectively avoids interference between the electrodes and improves the performance of the sensor. The length difference design of different flexible substrates in the needle contact area 4 allows the working electrode 22b and the reference electrode 12b to be exposed so as to contact the detection object. The setting of the positioning hole 6 and the external terminal facilitates the installation of the sensor and signal transmission. Compared with the traditional biosensor preparation process, this design simplifies the process, reduces the risk of short circuit, and can achieve flexible shape design through technologies such as laser engraving to meet different application requirements.

[0039] Example 2 Reference Figure 4 and Figure 5 The difference between this embodiment and the first embodiment is that the counter electrode film 30, the working electrode film 20, and the reference electrode film 10 are arranged in the same direction, and the third flexible substrate 31, the second flexible substrate 21, and the first flexible substrate 11 have different lengths in the needle contact area 4, so that the needle contact area 4 of the soft needle laminate body exposes the counter electrode 32, the working electrode 22b, and the reference electrode 12b in a step-by-step manner starting from the needle tip; this arrangement can also achieve effective contact between the electrodes and the detection object, and the exposure order of each electrode may have different effects on the detection results, which can be selected according to specific detection requirements.

[0040] The implementation principle of this embodiment is: by changing the arrangement direction of the electrode film and the length difference of the flexible substrate, the exposure order of the electrodes in the needle contact area 4 is changed, which provides more possibilities for the design of the sensor, can better adapt to different detection scenarios and needs, and further improves the applicability and flexibility of the sensor.

[0041] Example 3 The present invention also discloses a method for manufacturing a flexible implantable biosensor, comprising the following steps: S1, prepare reference electrode film 10, reference Figure 6 A reference electrode layer 12 is formed on the first flexible substrate 11 by a printing process. The reference electrode layer 12 includes a first wire line 12a and a reference electrode 12b connected to the first wire line 12a and configured in the needle contact area 4. The printing process can be screen printing or inkjet printing. Before printing the reference electrode layer 12, the first flexible substrate 11 needs to be cleaned to ensure the adhesion of the electrode layer. The reference electrode 12b can be made of silver, silver chloride, or a mixture of silver and silver chloride.

[0042] S2, prepare working electrode film 20, reference Figure 7 The working electrode layer 22 is formed on the second flexible substrate 21 by a printing process. The working electrode layer 22 includes a second wire line 22a and a working electrode 22b connected to the second wire line 22a and arranged in the needle contact area 4. The material used for the working electrode 22b is one or more of carbon, platinum carbon or carbon nanotubes. When printing the working electrode layer 22, it is important to control the thickness and uniformity of the printing to ensure the performance of the working electrode 22b. For details, please refer to Figure 7 .

[0043] S3, prepare the electrode film 30, reference Figure 8 The counter electrode layer is formed on the third flexible substrate 31 through a printing process, and the counter electrode layer includes a counter electrode 32. Similarly, before printing the counter electrode layer, the third flexible substrate 31 must be pretreated. The counter electrode 32 is generally made of carbon material or silver material, and there is no need to print special sensitive material parts.

[0044] S4. References Figure 9 The reference electrode film 10, the working electrode film 20 and the counter electrode film 30 are laminated together through a hot pressing process; wherein, in the hot pressing process, the hot pressing temperature used is 80-120°C, the pressure is 0.2-0.5MPa, the hot pressing time is 30-60 seconds, and the air between the functional layers can be removed by vacuum.

[0045] S5. Use laser engraving technology to perform graphic cutting on the laminated body of step S4 to form a soft needle laminated body. The soft needle laminated body has a needle contact area 4 and a mounting area 5. The second flexible substrate 21 and the first flexible substrate 11 have different lengths in the needle contact area 4, so that the needle contact area 4 of the soft needle laminated body reveals the working electrode 22b and the reference electrode 12b. Among them, the laser engraving technology can be selected from ultraviolet laser cutting or infrared laser cutting. The laser cutting tolerance is generally ±50μm. After the cutting is completed, the fine debris is removed by ultrasonic cleaning. For details, refer to Figure 10 .

[0046] Among them, reference Figures 6 to 8 , separate positioning holes 6 are formed on the reference electrode film 10, the working electrode film 20 and the electrode film respectively by using pre-laser engraving technology before the printing process, and a hollow area 13 is formed on the first flexible substrate 11 of the reference electrode film 10 by using pre-laser engraving technology before the printing process, so that the needle contact area 4 of the soft needle laminate in step S4 reveals the working electrode 22b in advance; and the single-layer conductive layer printing thickness of the reference electrode layer 12, the working electrode layer 22 and the counter electrode layer arranged by the above printing process can be 2-10μm, preferably 5-8μm; if an insulating layer needs to be covered, such as the outermost insulating layer, the thickness of the single-layer insulating layer can be 5-10μm.

[0047] The implementation principle of the embodiment of the present application is as follows: by preparing the reference electrode film 10, the working electrode film 20 and the counter electrode film 30 separately, then stacking them together using a hot pressing process, and finally forming them through laser engraving technology. This production method avoids the multiple precise alignments and complex curing processes in the traditional multi-layer screen printing process, reduces the process difficulty and short circuit risk, and improves production efficiency. The reasonable setting and parameter control of each step ensure the performance and quality of the sensor; by using the positioning holes 6 for alignment, the accuracy of the printing process is improved, and the accurate position of each electrode layer is ensured. The hollow area 13 is formed in advance on the reference electrode film 10, so that the working electrode 22b is exposed in advance, which simplifies the subsequent production process, and also reduces the impact of laser engraving on the working electrode 22b, thereby improving the yield and performance stability of the sensor.

[0048] Example 4 refer to Figure 11 The embodiment of the present application also discloses a method for manufacturing a flexible implantable biosensor, which is different from the third embodiment in that: the reference electrode film 10, the working electrode film 20 and the electrode film are respectively formed with edge marks 7 by pre-laser engraving technology before the printing process; the material used for the working electrode 22b is graphene and one or more of carbon, platinum carbon or carbon nanotubes, which are prepared into a composite material by chemical blending or physical mixing to enhance the laser tolerance of the working electrode 22b, so that the needle contact area 4 of the soft needle laminate in step S5 can be removed by laser engraving technology to remove the first flexible substrate 11 superimposed on the working electrode 22b to reveal the working electrode 22b, wherein the graphene and carbon are in a ratio of 1:2 to 1:5, or in a ratio of 1:1 to 1:3 with platinum carbon, or in a ratio of 1:3 to 1:6 with carbon nanotubes.

[0049] The implementation principle of this embodiment is: graphene is selected with one or more materials such as carbon, platinum carbon or carbon nanotubes through chemical blending or physical mixing to form a composite material as the material of the working electrode 22b, thereby enhancing the laser tolerance of the working electrode 22b, so that in step S5, the first flexible substrate 11 superimposed on the working electrode 22b can be removed by laser engraving technology to reveal the working electrode 22b. There is no need for a reference electrode film 10 to form a hollow area on the first flexible substrate 11 using pre-laser engraving technology before the printing process, so that the needle contact area 4 of the soft needle laminate in step S4 reveals the working electrode 22b in advance, which greatly simplifies the process flow and improves production efficiency.

[0050] Example 5 refer to Figure 12 The embodiment of the present application discloses a method for manufacturing a flexible implantable biosensor, which differs from the above-mentioned embodiment 4 in that: after step S5, an electrochemically active layer 8 is formed on the electrode surfaces of the reference electrode 12b and the working electrode 22b by deposition or attachment, and a biocompatible protective layer 9 is coated on the non-electrode surface of the sensor; the electrochemically active layer 8 can enhance the detection performance of the electrode, and the biocompatible protective layer 9 can improve the adaptability and safety of the sensor in the organism; and an insulating layer or an adhesive layer can be set between any two thin films to prevent electrical short circuits and enhance mechanical strength.

[0051] The working principle of this embodiment is as follows: Adding an electrochemically active layer 8 and a biocompatible protective layer 9 to a prefabricated sensor further enhances the sensor's performance and applicability. The electrochemically active material reacts more effectively with the target, improving detection sensitivity and accuracy. The biocompatible protective layer 9 reduces adverse reactions between the sensor and the organism, extending the sensor's service life and making it more suitable for in vivo use.

[0052] Example 6 The embodiment of the present application discloses a method for manufacturing a flexible implantable biosensor, which differs from the above-mentioned embodiment 5 in that: a small amount of nano-metal particles are doped into the graphene particles to improve conductivity while ensuring toughness; and in the hot pressing process, the hot pressing temperature used is 90-100°C and the pressure is 0.3-0.4MPa to reduce the compression rate of the conductive layer to 15%-20%; step S4 includes a UV pre-curing process before the hot pressing process; and the laser engraving technology in step S5 includes wavelength switching technology.

[0053] The implementation principle of this embodiment is: adding a UV pre-curing process before the hot pressing process helps to improve the initial bonding strength and stability between the films. The wavelength switching technology enables the laser engraving to flexibly adjust the wavelength according to the characteristics of different materials, improve the cutting accuracy and efficiency, and ensure the forming quality of the soft needle laminate.

[0054] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present application, rather than to limit them. Although the present application has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some or all of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the technical solutions of the embodiments of the present application.

Claims

1. A flexible implantable biosensor, characterized in that: include: A reference electrode film (10) comprising a first flexible substrate (11) and an independent reference electrode layer (12) formed on the first flexible substrate (11), wherein the reference electrode layer (12) comprises a first wire circuit (12a) and a reference electrode (12b) connected to the first wire circuit (12a) and arranged in the needle contact area (4); A working electrode film (20) comprising a second flexible substrate (21) and a composite working electrode layer (22) formed on the second flexible substrate (21), wherein the working electrode layer (22) comprises a second wire circuit (22a) and a working electrode (22b) connected to the second wire circuit (22a) and arranged in the needle contact area (4); A counter electrode film (30) comprising a third flexible substrate (31) and a counter electrode (32) layer formed on the third flexible substrate (31), wherein the counter electrode (32) layer comprises a counter electrode (32); The reference electrode film (10), the working electrode film (20) and the counter electrode film (30) are combined together by hot pressing and laminating to form a soft needle laminate, wherein the soft needle laminate has a needle contact area (4) and a mounting area (5), and the second flexible substrate (21) and the first flexible substrate (11) have different lengths in the needle contact area (4), so that the needle contact area (4) of the soft needle laminate exposes the working electrode (22b) and the reference electrode (12b).

2. The flexible implantable biosensor according to claim 1, characterized in that: The reference electrode layer (12), the working electrode layer (22), and the counter electrode (32) layer are stacked in sequence in a vertical direction and remain independent of each other, and the soft needle laminate is provided with a positioning hole (6) penetrating the reference electrode film (10), the working electrode film (20), and the counter electrode film (30) in the installation area (5).

3. The flexible implantable biosensor according to claim 2, characterized in that: The working electrode layer (22) is located between the reference electrode (12b) and the counter electrode (32) layer, and the working electrode film (20) and the reference electrode film (10) are stacked in a positive direction, so that the working electrode layer (22) and the reference electrode layer (12) are arranged in the same direction, and the counter electrode film (30) and the working electrode film (20) are stacked in a negative direction, so that the counter electrode (32) layer and the working electrode layer (22) are arranged in a reverse direction, so that the needle contact area (4) of the soft needle laminate body reveals the working electrode (22b) located on the front, the reference electrode (12b) and the counter electrode (32) located on the back.

4. The flexible implantable biosensor according to claim 2, characterized in that: The counter electrode film (30), the working electrode film (20) and the reference electrode film (10) are arranged in the same direction, and the third flexible substrate (31), the second flexible substrate (21) and the first flexible substrate (11) have different lengths in the needle contact area (4), so that the needle contact area (4) of the soft needle laminate is exposed in a step-by-step manner starting from the needle tip to the counter electrode (32), the working electrode (22b) and the reference electrode (12b).

5. The flexible implantable biosensor according to claim 1, characterized in that: The installation area (5) of the soft needle laminate has a bending portion (51), and the first wire circuit (12a), the second wire circuit (22a) and the counter electrode (32) are staggered at the bending portion (51), so that the installation area (5) of the soft needle laminate exposes the external connection ends of the first wire circuit (12a), the second wire circuit (22a) and the counter electrode (32).

6. The flexible implantable biosensor according to any one of claims 1 to 5, characterized in that: The needle contact area (4) and the installation area (5) are integrally connected and formed in the same laser cutting area.

7. A method for manufacturing a flexible implantable biosensor, characterized in that: The following steps are involved: S1. preparing a reference electrode film (10), and forming a reference electrode layer (12) on a first flexible substrate (11) by a printing process, wherein the reference electrode layer (12) comprises a first wire circuit (12a) and a reference electrode (12b) connected to the first wire circuit (12a) and arranged in the needle contact area (4); S2, preparing a working electrode film (20), and forming a working electrode layer (22) on a second flexible substrate (21) by a printing process, wherein the working electrode layer (22) includes a second wire circuit (22a) and a working electrode (22b) connected to the second wire circuit (22a) and arranged in the needle contact area (4); S3, preparing a counter electrode film (30), and forming a counter electrode (32) layer on a third flexible substrate (31) by a printing process, wherein the counter electrode (32) layer includes a counter electrode (32); S4, laminating the reference electrode film (10), the working electrode film (20) and the counter electrode film (30) together through a hot pressing process; S5. Use laser engraving technology to perform graphic cutting on the stacked body of step S4 to form a soft needle stacked body, wherein the soft needle stacked body has a needle contact area (4) and a mounting area (5), and the second flexible substrate (21) and the first flexible substrate (11) have different lengths in the needle contact area (4), so that the needle contact area (4) of the soft needle stacked body exposes the working electrode (22b) and the reference electrode (12b).

8. The method for manufacturing a flexible implantable biosensor according to claim 7, wherein: In the hot pressing process of step S4 , the hot pressing temperature is 80–120° C., the pressure is 0.2–0.5 MPa, the hot pressing time is 30–60 seconds, and the air between the functional layers is removed by vacuum.

9. The method for manufacturing a flexible implantable biosensor according to claim 7, wherein: The reference electrode film (10), the working electrode film (20) and the electrode film are aligned using separate positioning holes (6) or edge marks (7) during the printing process; and the reference electrode film (10) is provided with a hollow area (13) on the first flexible substrate (11) using a pre-laser engraving technique before the printing process, so that the needle contact area (4) of the soft needle laminate in step S4 reveals the working electrode (22b) in advance.

10. The method for manufacturing a flexible implantable biosensor according to claim 6, wherein: In step S2, the material used for the working electrode (22b) is graphene and one or more of carbon, platinum carbon or carbon nanotubes, which are prepared into a composite material by chemical blending or physical mixing to enhance the laser tolerance of the working electrode (22b), so that the needle contact area (4) of the soft needle laminate in step S5 can be removed by laser engraving technology from the first flexible substrate (11) superimposed on the working electrode (22b) to expose the working electrode (22b); after step S5, the electrode surfaces of the reference electrode (12b) and the working electrode (22b) are formed into an electrochemically active layer (8) by deposition or attachment, and a biocompatible protective layer (9) is coated on the non-electrode surface of the sensor; step S4 includes a UV pre-curing process before the hot pressing process; the laser engraving technology of step S5 includes a wavelength switching technology.

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