Flexible hydrogel neural electrode and preparation method and application thereof

Abstract

The invention discloses a flexible hydrogel neural electrode and a preparation method and application thereof. The flexible hydrogel neural electrode comprises a flexible substrate layer, an electrode layer and a packaging layer which are sequentially arranged in a stacked mode, the flexible substrate layer and the packaging layer are each of a hydrogel fiber composite film structure formed by compounding a fiber film and hydrogel, and the fiber film is embedded in the hydrogel; the fiber film is a polycaprolactam fiber film, and the hydrogel is polyvinyl alcohol hydrogel; the electrode layer comprises a plurality of metal electrodes, and each metal electrode is provided with an electrode point and a bonding pad; the packaging layer is provided with a plurality of hole structures, and the holes are arranged corresponding to the electrode points and the bonding pads and enable the electrode points and the bonding pads to be exposed. The flexible hydrogel neural electrode provided by the invention has good biocompatibility, swelling resistance and process compatibility; meanwhile, the flexible hydrogel neural electrode can be stably applied to an implantable brain-computer interface and is used for realizing long-term stable acquisition and transmission of neural signals.

Description

Technical Field

[0001] This invention belongs to the fields of flexible electronics, neural engineering and biosensing technology, specifically relating to a flexible hydrogel neural electrode and its preparation method and application. Background Technology

[0002] Implantable flexible neural electrodes are key interfaces for information interaction between the brain and external devices, and have significant application value in neuroscience research, diagnosis and treatment of neurological diseases, and brain-computer interfaces. Existing flexible neural electrodes typically use polymers such as polyimide (PI), polyethylene terephthalate (PET), and polyethylene terephthalate (PEN) as substrates. While these materials possess flexibility and processability to a certain extent, they still present the following problems: First, the biocompatibility of the materials themselves is limited, and long-term implantation can easily trigger inflammatory responses; second, the Young's modulus of these polymer materials is generally in the GPa range, which presents a significant mechanical mismatch with soft brain tissue (ranging from several hundred Pa to kPa), easily leading to chronic tissue damage and scar formation in the implantation area, thereby affecting the long-term stability of the electrode signal.

[0003] To improve the stability and performance of flexible neural electrodes, an encapsulation layer is typically introduced outside the electrode structure. This encapsulation layer must simultaneously possess good insulation, swelling resistance, and biostability. However, while traditional encapsulation materials such as polyimide (PI) have excellent insulation properties and a certain degree of chemical stability, their processing requires high-temperature curing, resulting in weak interfacial bonding with flexible substrates or hydrogel materials. This can easily lead to delamination and leakage during long-term use, causing encapsulation failure. Furthermore, with the increasing demand for high-density electrode arrays, traditional hydrogel substrates are limited by the compatibility of micro / nano fabrication processes, making it difficult to achieve the precise fabrication of micron-level channel spacing and large-scale electrode points.

[0004] In recent years, hydrogels have been considered promising new materials for neural electrodes due to their excellent biocompatibility, tunable mechanical properties, and Young's modulus similar to that of soft tissue. As a substrate or encapsulation layer for flexible electrodes, hydrogels are expected to significantly reduce tissue reaction and improve the long-term stability of the electrode-tissue interface. However, hydrogels still face many challenges in implantable flexible neural electrode applications: First, hydrogels are prone to swelling in body fluid environments, leading to device dimensional instability, interface failure, and even damage to electrode signal quality. Second, most hydrogels lack compatibility with standard micro / nano fabrication processes, making it difficult to directly apply photolithography, metal deposition, etching, and other processes, thus limiting their application in high-precision and high-throughput neural electrode fabrication. Furthermore, the long-term mechanical stability and degradation resistance of hydrogels still need further improvement to meet the reliability requirements of long-term implantation. Therefore, developing novel hydrogel-based flexible neural electrode structures with good biocompatibility, swelling resistance, and process compatibility has become a core problem urgently needing to be solved in this field. Summary of the Invention

[0005] The main objective of this invention is to provide a flexible hydrogel neural electrode, its preparation method, and its application, achieving the combination of hydrogel and a fine-linewidth metal electrode array. This flexible neural electrode uses a hydrogel with excellent biocompatibility, and improves its anti-swelling properties by forming a composite encapsulation film through electrospinning. Combined with micro-nano fabrication processes, a high-density flexible neural electrode based on a hydrogel substrate is designed and realized, meeting the requirements for high-resolution neural signal detection. This solves the problems of poor biocompatibility, low tissue compatibility, easy swelling, and insufficient process compatibility of existing neural electrodes.

[0006] To achieve the aforementioned objectives, the technical solution adopted by this invention includes: This invention provides a flexible hydrogel neural electrode, comprising a flexible substrate layer, an electrode layer, and an encapsulation layer stacked sequentially. The flexible substrate layer and the encapsulation layer are both hydrogel-fiber composite film structures formed by combining a fiber film and a hydrogel, with the fiber film embedded inside the hydrogel. The fiber film is a polycaprolactam (PA66) fiber film, and the hydrogel is a polyvinyl alcohol (PVA) hydrogel. The electrode layer comprises a plurality of metal electrodes, each of which has an electrode point and a pad; The encapsulation layer is provided with a plurality of opening structures, and the openings are provided corresponding to the electrode points and pads, thereby exposing the electrode points and pads.

[0007] This invention also provides a method for preparing the aforementioned flexible hydrogel neural electrode, comprising: A sacrificial layer is prepared on the surface of a silicon wafer using photolithography and magnetron sputtering techniques. A fiber film is prepared on the surface of the sacrificial layer using electrospinning technology. Then, a hydrogel solution is spin-coated onto the surface of the fiber film and subjected to thermal curing to form a hydrogel fiber composite film, thereby obtaining a flexible substrate layer. Electrode layers are fabricated on the surface of a flexible substrate using photolithography, electron beam evaporation, or magnetron sputtering. Furthermore, the aforementioned steps are repeated to prepare a hydrogel fiber composite film on the surface of the electrode layer, and then photolithography and plasma etching are used to expose the electrode points and pads in the electrode layer to form an encapsulation layer, thereby obtaining the flexible hydrogel neural electrode.

[0008] This invention also provides the application of the aforementioned flexible hydrogel neural electrode in the fabrication of a flexible brain-computer interface.

[0009] This invention also provides a neural signal acquisition and transmission system, which includes the aforementioned flexible hydrogel neural electrode.

[0010] Compared with the prior art, the beneficial effects of the present invention are as follows: (1) The present invention uses a flexible base layer of "PA66 fiber film embedded in PVA hydrogel", which not only retains the mechanical matching between hydrogel and soft brain tissue (Young's modulus kPa level), but also reduces tissue damage and inflammatory response caused by long-term implantation; at the same time, the fiber film can inhibit the swelling and deformation of hydrogel in body fluid, improve the dimensional stability of the device, and completely solve the problems of "unstable size and interface failure" of traditional hydrogel electrodes. (2) The hydrogel fiber composite film in this invention can be adapted to MEMS processes such as photolithography, magnetron sputtering, and plasma etching, and can achieve fine control of "electrode point size 20~50μm and adjacent spacing 100~200μm", supporting the array preparation of micron-level channel spacing and electrode points, breaking the limitation of traditional hydrogel electrodes being "difficult to process finely"; (3) In this invention, the base layer and the encapsulation layer of the electrode adopt the same hydrogel fiber composite structure, which avoids the delamination and leakage problems of long-term implantation and extends the service life of the device. (4) The electrodes of the present invention can reduce scar tissue encapsulation after implantation, and can still stably collect high-quality neural electrical signals after 10 weeks of continuous implantation, solving the pain point of "long-term signal quality decay" of traditional electrodes, and meeting the needs of diagnosis and treatment of neurological diseases (epilepsy, Parkinson's disease) and scientific research-level EEG research. Attached Figure Description

[0011] To more clearly illustrate the technical solutions in the embodiments of this application or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments recorded in this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0012] Figure 1 This is a schematic diagram of a hydrogel fiber composite film in a typical embodiment of the present invention; Figure 2 This is a schematic diagram of a flexible hydrogel neural electrode in a typical embodiment of the present invention; Figure 3 This is a schematic diagram of the tip of a flexible hydrogel neural electrode in a typical embodiment of the present invention; Figure 4 This is a physical image of the flexible hydrogel neural electrode prepared in Example 1 of the present invention; Figure 5 This is a scanning electron microscope image of the hydrogel fiber composite film prepared in Example 1 of the present invention; Figure 6 This is an atomic force microscope image of the surface of the hydrogel fiber composite film prepared in Example 1 of the present invention; Figure 7 These are mechanical test diagrams of the hydrogel fiber composite film prepared in Example 1 of this invention; Figure 8 This is an optical image of the electrode layer pattern in the flexible hydrogel neural electrode prepared in Example 1 of this invention; Figure 9 This is a scanning electron microscope image of the cross-section of the flexible hydrogel neural electrode prepared in Example 1 of the present invention; Figure 10 This is an impedance test diagram of the flexible hydrogel neural electrode prepared in Example 1 of the present invention; Figure 11 This is an actual neural signal waveform diagram of the flexible hydrogel neural electrode prepared in Embodiment 1 of the present invention used for brain neural acquisition; Figures 12a-12b These are scanning electron microscope images of the surface of the hydrogel fiber composite film of Example 1 and Comparative Example 4 of the present invention; Figure 13 These are physical optical images of the flexible hydrogel neural electrodes of Embodiment 1 and Comparative Example 1 of the present invention; Figure 14 This is a cell biocompatibility diagram of Example 1 and Comparative Example 1 of the present invention. Detailed Implementation

[0013] In view of the deficiencies of the prior art, the technical solution of the present invention is proposed. The technical solution of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0014] Specifically, as one aspect of the technical solution of the present invention, a flexible hydrogel neural electrode includes a flexible base layer, an electrode layer, and an encapsulation layer stacked sequentially. The flexible base layer and the encapsulation layer are both hydrogel-fiber composite film structures formed by combining fiber films and hydrogels, and the fiber films are embedded inside the hydrogels. The fiber films are polycaprolactam (PA66) fiber films, and the hydrogels are polyvinyl alcohol (PVA) hydrogels. The electrode layer comprises a plurality of metal electrodes, each of which has an electrode point and a pad; The encapsulation layer is provided with a plurality of opening structures, and the openings are provided corresponding to the electrode points and pads, thereby exposing the electrode points and pads.

[0015] The flexible substrate and encapsulation layer described in this invention are both hydrogel fiber composite film structures formed by embedding polycaprolactam (PA66) fiber films inside polyvinyl alcohol (PVA) hydrogels. This composite film structure can suppress the swelling of the hydrogel in a body fluid environment, ensuring the dimensional stability of the device and the reliability of the interface bonding. The hydrogel fiber composite film is compatible with micro-nano processing technologies such as photolithography, metal deposition, and etching, and can realize the arrayed fabrication of micron-level channel spacing and electrode points.

[0016] In some preferred embodiments, a schematic diagram of the hydrogel fiber composite film of the present invention is shown below. Figure 1 As shown.

[0017] In some preferred embodiments, a schematic diagram of the flexible hydrogel neural electrode of the present invention is shown below. Figure 2 As shown.

[0018] In some preferred embodiments, a schematic diagram of the tip of the flexible hydrogel neural electrode in this invention is shown below. Figure 3 As shown.

[0019] In some preferred embodiments, the thickness of the flexible substrate layer is 1~5μm.

[0020] In some preferred embodiments, the thickness of the encapsulation layer is 1~5μm.

[0021] In some preferred embodiments, the electrode layer adopts a chromium / gold composite structure with a thickness of 5nm / 100nm; the diameter of the electrode point is 20~50μm, and the spacing between adjacent electrode points is 100~200μm.

[0022] In some preferred embodiments, the thickness of the flexible hydrogel neural electrode is less than 10 μm.

[0023] Another aspect of the present invention provides a method for preparing the aforementioned flexible hydrogel neural electrode, comprising: A sacrificial layer is prepared on the surface of a silicon wafer using photolithography and magnetron sputtering techniques. A fiber film is prepared on the surface of the sacrificial layer using electrospinning technology. Then, a hydrogel solution is spin-coated onto the surface of the fiber film and subjected to thermal curing to form a hydrogel fiber composite film, thereby obtaining a flexible substrate layer. Electrode layers are fabricated on the surface of a flexible substrate using photolithography, electron beam evaporation, or magnetron sputtering. Furthermore, the aforementioned steps are repeated to prepare a hydrogel fiber composite film on the surface of the electrode layer, and then photolithography and plasma etching are used to expose the electrode points and pads in the electrode layer to form an encapsulation layer, thereby obtaining the flexible hydrogel neural electrode.

[0024] In some preferred embodiments, the preparation method specifically includes: forming a sacrificial layer pattern on the surface of a silicon wafer using photolithography, and then depositing a metal layer as a sacrificial layer on the surface of the silicon wafer using magnetron sputtering; wherein the metal includes aluminum and / or nickel; and the thickness of the sacrificial layer is 100~500nm.

[0025] In some preferred embodiments, the preparation method specifically includes: A fiber film was prepared on the surface of the sacrificial layer using electrospinning technology; wherein the concentration of the PA66 spinning solution used was 9~21wt%; the process parameters used in the electrospinning technology included: voltage of 15~25kV, receiving distance of 10~20cm, spinning rate of 0.5~2mL / h, and spinning time of 30~300s. Furthermore, a PVA hydrogel solution is spin-coated onto the surface of the fiber film and then thermosetting to form a flexible substrate layer; wherein the concentration of the PVA hydrogel solution is 5~15wt%; the spin-coating speed is 1000~5000rpm, the spin-coating time is 20~40s, and the film thickness is 1~5μm; the thermosetting temperature is 100~180℃, and the heating time is 20~40min.

[0026] In some preferred embodiments, the preparation method specifically includes: preparing a photoresist film on the surface of a flexible substrate by spin coating, then patterning the photoresist film using photolithography, then depositing an electrode layer material using electron beam evaporation, and finally peeling off the photoresist to obtain the electrode layer; wherein the electrode layer material includes a 5nm / 100nm thick chromium / gold alloy.

[0027] In some preferred embodiments, the preparation method specifically includes: A fiber film was prepared on the surface of the electrode layer by electrospinning technology. Then, a PVA hydrogel solution was spin-coated onto the surface of the fiber film and subjected to thermal curing to obtain a hydrogel fiber composite film. A photoresist film was prepared on the surface of a hydrogel fiber composite film by spin coating. The photoresist film was then patterned by photolithography and then etched by plasma etching to expose the electrode points and pads. Furthermore, the sacrificial layer is removed to release the electrode from the silicon wafer, thereby obtaining a flexible hydrogel neural electrode.

[0028] Furthermore, the sacrificial layer is made of aluminum or nickel, and the sacrificial layer is removed in a metal etching solution of the metal to release the electrode from the silicon wafer.

[0029] This invention combines hydrogel micro-nano fabrication technology compatible with microelectromechanical systems (MEMS) processes to construct an ultra-flexible hydrogel layer; then, it combines masking, photolithography, metal evaporation or sputtering to obtain an electrode layer; finally, it uses RIE etching technology to precisely control the electrode morphology at specific points, thereby realizing a flexible neural electrode that can work stably in vivo for a long time.

[0030] In some preferred embodiments, the method for preparing the flexible hydrogel neural electrode includes the following steps: Step 1: Clean the silicon wafer; Step 2: A sacrificial layer pattern is formed on the surface of the processed silicon wafer using photolithography. Step 3: Deposit a metal layer as a sacrificial layer on the silicon wafer surface using magnetron sputtering technology; Step 4: Prepare a fiber film on the surface of the sacrificial layer using electrospinning technology; Step 5: Prepare a hydrogel-fiber composite film on the surface of the fiber film obtained in Step 4 using a spin-coating process, and then heat-cur it. This composite film serves as the bottom insulating layer (i.e., the flexible substrate layer). Step 6: Form a metal electrode array pattern on the surface of the composite thin film obtained in step 5 by photolithography; Step 7: Prepare a metal electrode array (i.e., electrode layer) on the surface of the hydrogel fiber composite film using electron beam evaporation technology. Step 8: Repeat steps 4 and 5 to prepare a hydrogel fiber composite film on the surface of the metal electrode as a top insulating layer (i.e., encapsulation layer). Step 9: Prepare electrode shape patterns on the surface of the top insulating layer by photolithography; Step 10: Using plasma etching technology, an electrode outline is formed based on the photolithography pattern, and the electrode points at the front end and the pads at the rear end are exposed to obtain a flexible neural electrode; Step 11: Peel the flexible neural electrode off the sacrificial layer to obtain the flexible neural electrode.

[0031] Preferably, a silicon wafer is first provided, and then a sacrificial layer is formed on the surface of the silicon wafer. The sacrificial layer is deposited by magnetron sputtering with a 100nm thick layer of metallic aluminum, which is used to finally release the flexible electrode from the silicon wafer.

[0032] Preferably, a fiber film is formed on the sacrificial layer by electrospinning. The spinning solution is PA66 with a concentration of 9~21wt%. The specific electrospinning process parameters are: voltage 15~25kV, receiving distance 10~20cm, spinning rate 0.5-2mL / h, and spinning time 30~300s.

[0033] Preferably, a PVA solution is spin-coated onto the surface of the fiber film to form a hydrogel fiber composite film as a flexible substrate layer. The hydrogel material is polyvinyl alcohol (PVA), and its preparation process is as follows: PVA is added to deionized water and dissolved under conditions of heating temperature 60~90℃ and stirring speed 300~500rpm to obtain a PVA solution, wherein the concentration of PVA is 5~15wt%. The spin-coating speed is 1000~3000rpm, the spin-coating time is 20~40s, the film thickness is 1~5μm, and then it is cured by heating at a temperature of 100~180℃ for 20~40 minutes.

[0034] Preferably, a photoresist film, such as an AZ5214 photoresist film, is spin-coated onto the surface of a flexible substrate. The photoresist is patterned using photolithography, and then an electrode layer material is deposited by electron beam evaporation. The electrode material is a 5nm / 100nm thick chromium / gold (Cr / Au) alloy. The chromium / gold alloy has relatively stable chemical properties and good biocompatibility. The photoresist is then peeled off using a lift-off process to form the electrode layer structure.

[0035] Preferably, a PVA hydrogel layer is formed on the surface of the electrode layer as an encapsulation layer. In one specific implementation, the encapsulation layer is formed by spin-coating a PVA solution, with a thickness of 1~5μm.

[0036] Preferably, a photoresist film is spin-coated onto the surface of the encapsulation layer, and the photoresist is patterned using photolithography. Then, the encapsulation layer is etched using RIE etching technology to form the front and rear openings of the electrode and the overall outline of the electrode.

[0037] Preferably, the sacrificial layer is removed to release the electrode from the silicon wafer, resulting in a hydrogel flexible neural electrode based on micro / nano fabrication. PVA hydrogels exhibit excellent corrosion resistance to common metal etchants, such as aluminum etchants, which can be used to release the electrode from the silicon wafer.

[0038] The flexible deep brain electrode manufactured through the above steps has an overall thickness of less than 10 μm, which makes the bending force of the electrode equivalent to the stretching force of nerve tissue, without causing shear damage, and improving the long-term stability after electrode implantation.

[0039] Another aspect of the present invention provides the application of the aforementioned flexible hydrogel neural electrode in the fabrication of a flexible brain-computer interface.

[0040] Another aspect of the present invention provides a neural signal acquisition and transmission system, which includes the aforementioned flexible hydrogel neural electrode.

[0041] The technical solution of the present invention will be further described in detail below with reference to several preferred embodiments and accompanying drawings. This embodiment is implemented on the premise of the technical solution of the invention, and provides detailed implementation methods and specific operation processes. However, the protection scope of the present invention is not limited to the following embodiments.

[0042] Unless otherwise specified, the experimental materials used in the examples below can be purchased from conventional biochemical reagent companies.

[0043] Example 1 Step 1: Clean the silicon wafer; Step 2: A sacrificial layer pattern is formed on the surface of the processed silicon wafer using photolithography. Step 3: Deposit a 100nm thick layer of metallic aluminum by magnetron sputtering; Step 4: Prepare a fiber film on the surface of the sacrificial layer by electrospinning technology; the spinning solution is PA66 with a concentration of 15wt%, and the specific electrospinning process parameters are: voltage 20kV, receiving distance 15cm, spinning rate 0.5mL / h, and spinning time 60s. Step 5: Spin-coat a PVA solution onto the surface of the fiber film to form a hydrogel fiber composite film as a flexible substrate layer; wherein, the hydrogel material is polyvinyl alcohol (PVA), and its preparation process is as follows: PVA is added to deionized water and dissolved under the conditions of heating temperature of 70℃ and stirring speed of 400rpm to obtain a PVA solution with a concentration of 10wt%, spin-coating speed of 2000rpm, spin-coating time of 30s, film thickness of 3μm, and then heated and cured at a temperature of 150℃ for 30min; Step 6: Spin-coat a photoresist film onto the surface of the flexible substrate, and pattern the photoresist using photolithography to form a metal electrode array pattern; Step 7: Electrode layer material is deposited by electron beam evaporation. The electrode material is a 5nm / 100nm thick chromium / gold (Cr / Au) alloy. The photoresist is removed by a lift-off process to form the electrode layer. Step 8: Repeat steps 4 and 5 to prepare a hydrogel fiber composite film on the surface of the electrode layer as a top insulating layer (i.e., encapsulation layer). Step 9: Spin-coat a thin film of photoresist onto the surface of the encapsulation layer, and pattern the photoresist using photolithography. Step 10: Use plasma etching technology to form the electrode outline according to the photolithography pattern, and expose the electrode front electrode point and the rear pad. Step 11: Remove the sacrificial layer using a metal etching solution to release the electrode from the silicon wafer, thus obtaining a flexible hydrogel neural electrode, such as... Figure 4 As shown.

[0044] Characterization: The scanning electron microscope image of the hydrogel fiber composite film prepared in step 5 of this embodiment is shown below. Figure 5 As shown, the PA66 fiber film exhibits a continuous network structure, completely embedded within the PVA hydrogel matrix. There are no obvious pores between the fibers and the hydrogel, and the interface is tightly bonded. This structure provides mechanical support for the hydrogel through the fiber film while retaining the hydrogel's flexibility, and simultaneously provides a stable substrate for subsequent electrode layer deposition. Surface atomic force microscopy images are shown below. Figure 6 As shown, quantitative analysis revealed that its root mean square roughness (RMS) was only 6.5 nm. This low-roughness surface avoids film defects caused by substrate undulations during metal electrode deposition, ensuring the continuity and conductivity of the electrode layer and fully meeting the requirements of high-precision metal electrode fabrication processes. Mechanical test results are shown below. Figure 7 As shown, its elastic modulus is highly matched with the modulus of brain tissue, which avoids the defects of pure PVA hydrogel with low modulus and easy deformation, and avoids the mechanical mismatch between traditional rigid base and brain tissue. It can significantly reduce the mechanical damage to surrounding nerve tissue after long-term electrode implantation. The optical pattern of the electrode layer in the flexible hydrogel neural electrode prepared in this embodiment is shown in the figure below. Figure 8 As shown, the metal electrode array pattern is regular and clear. This result directly confirms the good compatibility between hydrogel fiber composite films and MEMS processes such as photolithography and metal deposition, realizing the precise fabrication of electrode arrays and laying the structural foundation for high-resolution neural signal acquisition. A scanning electron microscope image of the cross-section of the flexible hydrogel neural electrode prepared in this embodiment is shown below. Figure 9 As shown, the three-layer composite structure of the electrode, consisting of a flexible substrate layer, an electrode layer, and an encapsulation layer, is clearly presented, and the interface bonding is stable. The impedance test diagram of the flexible hydrogel neural electrode prepared in this embodiment is shown below. Figure 10 As shown, the low impedance electrical properties perfectly match the requirements of neural signal acquisition, ensuring efficient acquisition of neural electrical signals. The flexible hydrogel neural electrode prepared in this embodiment was used for brain nerve acquisition, and the actual acquired neural signal waveform is shown in the figure below. Figure 11 As shown, the typical spike waveform of the neuronal action potential is clearly presented, verifying its excellent neural signal acquisition capability.

[0045] The key performance indicators of the hydrogel fiber composite film and flexible hydrogel array electrode prepared in this embodiment are shown in Table 1.

[0046] Example 2 This embodiment provides a method for preparing a flexible hydrogel neural electrode, as detailed below: (1) Material proportions: The PA66 spinning solution concentration is 15wt%; the PVA solution concentration is 10wt%.

[0047] The raw material sources of PA66 and PVA in this embodiment are the same as those in Example 1.

[0048] (2) Preparation process: Except for the electrospinning time of 30s, the other process parameters are completely consistent with those in Example 1; The key performance indicators of the hydrogel fiber composite film and flexible hydrogel array electrode prepared in this embodiment are shown in Table 1.

[0049] Example 3 This embodiment provides a method for preparing a flexible hydrogel neural electrode, as detailed below: (1) Material proportions: The PA66 spinning solution concentration is 15wt%; the PVA solution concentration is 10wt%.

[0050] The raw material sources of PA66 and PVA in this embodiment are the same as those in Example 1.

[0051] (2) Preparation process: Except for the electrospinning time of 90s, the other process parameters are completely consistent with those in Example 1; The key performance indicators of the hydrogel fiber composite film and flexible hydrogel array electrode prepared in this embodiment are shown in Table 1.

[0052] Example 4 This embodiment provides a method for preparing a flexible hydrogel neural electrode, as detailed below: (1) Material proportions: The PA66 spinning solution concentration is 9wt%, and the PVA solution concentration is 10wt%.

[0053] The PA66 and PVA used in this embodiment are from the same sources as in Example 1.

[0054] (2) Preparation process: The process parameters are completely consistent with those of Example 1; The key performance indicators of the hydrogel fiber composite film and flexible hydrogel array electrode prepared in this embodiment are shown in Table 1.

[0055] Example 5 This embodiment provides a method for preparing a flexible hydrogel neural electrode, as detailed below: (1) Material proportions: The PA66 spinning solution concentration is 21wt%, and the PVA solution concentration is 10wt%.

[0056] The PA66 and PVA used in this embodiment are from the same sources as in Example 1.

[0057] (2) Preparation process: The process parameters are completely consistent with those of Example 1; The key performance indicators of the hydrogel fiber composite film and flexible hydrogel array electrode prepared in this embodiment are shown in Table 1.

[0058] Example 6 This embodiment provides a method for preparing a flexible hydrogel neural electrode, as detailed below: (1) Material proportions: The PA66 spinning solution concentration is 15wt%, and the PVA solution concentration is 10wt%.

[0059] The PA66 and PVA used in this embodiment are from the same sources as in Example 1.

[0060] (2) Preparation process: Except for the curing temperature of 180℃, the other process parameters are the same as in Example 1.

[0061] The key performance indicators of the hydrogel fiber composite film and flexible hydrogel array electrode prepared in this embodiment are shown in Table 1.

[0062] Example 7 This embodiment provides a method for preparing a flexible hydrogel neural electrode, as detailed below: (1) Material proportions: The PA66 spinning solution concentration is 15wt%, and the PVA solution concentration is 10wt%.

[0063] The PA66 and PVA used in this embodiment are from the same sources as in Example 1.

[0064] (2) Preparation process: Electrospinning: The process parameters are completely consistent with those in Example 1; PVA spin coating and curing: Except for the curing temperature of 120℃, the other process parameters are the same as in Example 1.

[0065] The key performance indicators of the hydrogel fiber composite film and flexible hydrogel array electrode prepared in this embodiment are shown in Table 1.

[0066] Comparative Example 1 The method for fabricating a flexible hydrogel array electrode provided in this comparative example differs from that in Example 1 only in that PVA hydrogel is used instead of hydrogel fiber composite film in this comparative example.

[0067] The key performance indicators of the flexible hydrogel array electrode prepared in this comparative example are shown in Table 1.

[0068] Comparative Example 2 The method for fabricating a flexible hydrogel array electrode provided in this comparative example differs from that in Example 1 only in that PA66 film is used instead of hydrogel fiber composite film in this comparative example.

[0069] The key performance indicators of the flexible hydrogel array electrode prepared in this comparative example are shown in Table 1.

[0070] Comparative Example 3 The difference between the method for fabricating a flexible hydrogel array electrode provided in this comparative example and Example 1 is that the encapsulation layer in this comparative example does not use electrospinning technology to prepare a fiber film, but uses PVA hydrogel instead of hydrogel fiber composite film.

[0071] The key performance indicators of the flexible hydrogel array electrode prepared in this comparative example are shown in Table 1.

[0072] Comparative Example 4 The method for fabricating a flexible hydrogel array electrode provided in this comparative example differs from that in Example 1 only in that the concentration of the PVA solution in this comparative example is 2wt%.

[0073] The key performance indicators of the flexible hydrogel array electrode prepared in this comparative example are shown in Table 1.

[0074] Comparative Example 5 The method for fabricating a flexible hydrogel array electrode provided in this comparative example differs from that in Example 1 only in that the concentration of the PVA solution in this comparative example is 20 wt%.

[0075] The key performance indicators of the flexible hydrogel array electrode prepared in this comparative example are shown in Table 1.

[0076] Comparative Example 6 The method for fabricating a flexible hydrogel array electrode provided in this comparative example differs from that in Example 1 only in that the film curing temperature in this comparative example is 70°C.

[0077] The key performance indicators of the flexible hydrogel array electrode prepared in this comparative example are shown in Table 1.

[0078] Comparative Example 7 The method for fabricating a flexible hydrogel array electrode provided in this comparative example differs from that in Example 1 only in that the film curing temperature in this comparative example is 200°C. Because the curing temperature is too high, the elastic modulus of the composite film is excessively high, resulting in a significant difference from the modulus of brain tissue. This can easily lead to tissue damage and signal attenuation after implantation, making it unsuitable for fabricating flexible neural electrodes.

[0079] The key performance indicators of the flexible hydrogel array electrode prepared in this comparative example are shown in Table 1.

[0080] Table 1. Key performance indicators of the hydrogel fiber composite films and flexible hydrogel array electrodes prepared in the examples and comparative examples.

[0081] Test Example 1 The surface morphology of the hydrogel fiber composite films of Example 1 and Comparative Example 4 was photographed using a scanning electron microscope. The test results are as follows: Figures 12a-12b As shown, the surface of the hydrogel fiber composite film in Example 1 is a continuous, flat and dense state with no obvious exposed fiber structure. Only a uniform film substrate texture can be observed. This difference in morphology directly reflects the necessity of the synergistic process of "PA66 fiber spinning + PVA spin coating and curing".

[0082] Test Example 2 The morphological changes of the flexible hydrogel array electrodes of Example 1 and Comparative Example 1 after immersion in physiological saline were observed using an optical microscope. The test results are as follows: Figure 13 As shown, after immersion, the flexible hydrogel array electrode of Example 1 exhibits a neat and orderly arrangement of wires, a clear and complete pattern, and a smooth substrate surface without obvious swelling or deformation. This fully demonstrates the excellent anti-swelling properties of its hydrogel fiber composite film substrate, which can effectively maintain the structural integrity of the electrode.

[0083] Test Example 3 Biocompatibility experiments were conducted on the flexible hydrogel array electrodes of Example 1 and Comparative Example 1, as well as the blank control group. The experimental results are as follows: Figure 14 As shown, the flexible hydrogel array electrode of Example 1 demonstrates that it is non-toxic to cells, and the cells still retain good cell activity.

[0084] In addition, with reference to the foregoing embodiments, experiments were conducted using other raw materials, process operations, and process conditions described in this specification, and all yielded relatively ideal results.

[0085] It should be understood that the technical solutions of the present invention are not limited to the specific embodiments described above. Any technical modifications made to the technical solutions of the present invention without departing from the spirit and scope of the claims are within the scope of protection of the present invention.

Claims

1. A flexible hydrogel neural electrode, characterized in that, The device includes a flexible substrate layer, an electrode layer, and an encapsulation layer stacked sequentially. The flexible substrate layer and the encapsulation layer are both hydrogel-fiber composite film structures formed by combining a fiber film and a hydrogel, with the fiber film embedded inside the hydrogel. The fiber film is a polycaprolactam fiber film, and the hydrogel is a polyvinyl alcohol hydrogel. The electrode layer comprises a plurality of metal electrodes, each of which has an electrode point and a pad; The encapsulation layer is provided with a plurality of opening structures, and the openings are provided corresponding to the electrode points and pads, thereby exposing the electrode points and pads.

2. The flexible hydrogel neural electrode according to claim 1, characterized in that: The thickness of the flexible substrate layer is 1~5μm; and / or, the thickness of the encapsulation layer is 1~5μm; And / or, the electrode layer adopts a chromium / gold composite structure with a thickness of 5nm / 100nm; the diameter of the electrode point is 20~50μm, and the spacing between adjacent electrode points is 100~200μm.

3. The flexible hydrogel neural electrode according to claim 1, characterized in that: The thickness of the flexible hydrogel neural electrode is less than 10 μm.

4. The method for preparing the flexible hydrogel neural electrode according to any one of claims 1-3, characterized in that, include: A sacrificial layer is prepared on the surface of a silicon wafer using photolithography and magnetron sputtering techniques. A fiber film was prepared on the surface of the sacrificial layer using electrospinning technology. Then, a PVA hydrogel solution was spin-coated onto the surface of the fiber film and subjected to thermal curing to form a hydrogel fiber composite film, thereby obtaining a flexible substrate layer. Electrode layers are fabricated on the surface of a flexible substrate using photolithography, electron beam evaporation, or magnetron sputtering. Furthermore, the aforementioned steps are repeated to prepare a hydrogel fiber composite film on the surface of the electrode layer, and then photolithography and plasma etching are used to expose the electrode points and pads in the electrode layer to form an encapsulation layer, thereby obtaining the flexible hydrogel neural electrode.

5. The preparation method according to claim 4, characterized in that, Specifically, it includes: A sacrificial layer pattern is formed on the surface of a silicon wafer using photolithography, and then a metal layer is deposited on the surface of the silicon wafer as a sacrificial layer using magnetron sputtering; wherein the metal includes aluminum and / or nickel; and the thickness of the sacrificial layer is 100~500nm.

6. The preparation method according to claim 4, characterized in that, Specifically, it includes: A fiber film was prepared on the surface of the sacrificial layer using electrospinning technology; wherein the concentration of the PA66 spinning solution used was 9~21wt%; the process parameters used in the electrospinning technology included: voltage of 15~25kV, receiving distance of 10~20cm, spinning rate of 0.5~2mL / h, and spinning time of 30~300s. Furthermore, a PVA hydrogel solution is spin-coated onto the surface of the fiber film and then thermosetting to form a flexible substrate layer; wherein the concentration of the PVA hydrogel solution is 5~15wt%; the spin-coating speed is 1000~5000rpm, the spin-coating time is 20~40s, and the film thickness is 1~5μm; the thermosetting temperature is 100~180℃, and the heating time is 20~40min.

7. The preparation method according to claim 4, characterized in that, Specifically, it includes: A photoresist film is prepared on the surface of a flexible substrate by spin coating. The photoresist film is then patterned using photolithography. Electron beam evaporation is then used to deposit an electrode layer material. Finally, the photoresist is stripped off to obtain the electrode layer. The electrode layer material includes a 5nm / 100nm thick chromium / gold alloy.

8. The preparation method according to claim 4, characterized in that, Specifically, it includes: A fiber film was prepared on the surface of the electrode layer by electrospinning technology. Then, a PVA hydrogel solution was spin-coated onto the surface of the fiber film and subjected to thermal curing to obtain a hydrogel fiber composite film. A photoresist film was prepared on the surface of a hydrogel fiber composite film by spin coating. The photoresist film was then patterned by photolithography and then etched by plasma etching to expose the electrode points and pads. Furthermore, the sacrificial layer is removed to release the electrode from the silicon wafer, thereby obtaining a flexible hydrogel neural electrode.

9. The use of the flexible hydrogel neural electrode according to any one of claims 1-3 in the preparation of a flexible brain-computer interface.

10. A neural signal acquisition and transmission system, characterized in that, Includes the flexible hydrogel neural electrode according to any one of claims 1-3.

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