Soft neural electrode based on micro-wrinkle and micro-pore composite interface and its preparation method

Abstract

The present invention discloses a soft neural electrode based on a composite interface of micro-wrinkles and micro-pores and a preparation method thereof, which is composed of a soft base layer, a flexible substrate layer, a conductive metal layer, a flexible packaging layer and a modified coating. The micro-electrode points exposed by the openings of the flexible packaging layer are composite interfaces composed of a micro-wrinkle structure and a micro-pore structure. The preparation method includes: 1. Spin coating and curing of a soft silicone material mixed with silicone oil, followed by soaking in an organic solvent to extract the silicone oil, to form a soft base layer; 2. Depositing a layer of polymer film on the surface as a flexible substrate layer to automatically form a micro-wrinkle structure; 3. Using a laser cutting process to form a micro-pore structure on the surface of the flexible substrate layer; 4. Using deposition, photolithography, and etching processes to sequentially form a conductive metal layer and a flexible packaging layer; 5. Using an electrochemical workstation to complete the deposition of the modified coating of the micro-electrode points. The present invention can effectively improve the long-term stability of the modified coating material on the surface of the micro-electrode points.

Description

Technical Field

[0001] The present invention belongs to the field of biomedical electronics technology, and in particular relates to a soft neural electrode and a preparation method thereof. Background Art

[0002] In recent years, probe-type flexible neural electrodes made of flexible polymer substrate materials such as polyimide and parylene are gradually becoming an important alternative to rigid Michigan probes. Because flexible neural electrodes not only have high micro-nano processing precision and low processing cost, but also can adapt to micro-movements of brain tissue, reduce damage during implantation and the formation of glial scars after long-term implantation. However, compared with the Young's modulus of soft brain tissue (0.4-15kPa), the Young's modulus of flexible polymer materials reaches several GPa, which is still about 5 orders of magnitude higher. New research shows that soft neural electrodes based on stretchable materials can better adapt to complex tissue deformation and movement, minimize tissue damage during deformation, and effectively reduce inflammation or rejection reactions, thereby avoiding the problem of decreased recording signal quality caused by the rapid increase in interface resistance that hinders charge transfer.

[0003] Since the electrode point size of the probe-type neural microelectrode is extremely small, how to ensure good and stable electrochemical performance under the trend of smaller and smaller microelectrode size has become one of the focuses of flexible or even soft neural electrodes. Polystyrene sulfonate (PEDOT:PSS) is one of the most commonly used conductive polymer modified materials. It not only has good biocompatibility, but also can effectively reduce surface impedance and improve the quality of collected signals. It has good application prospects. For example, the flexible electrode wire developed by Neuralink uses this surface modified material on a single gold microelectrode point with a size of 14×24 microns. However, due to the lack of strong covalent bonds after deposition on the metal electrode surface and the volume expansion and contraction when used in a physiological environment, the material has poor bonding with the metal electrode substrate and weak mechanical stability, which easily causes the PEDOT:PSS film on the electrode surface to crack or fall off completely.

[0004] One method is to increase the effective surface area of ​​the electrode point, which can improve the bonding force between the conductive polymer coating and the electrode substrate to a certain extent and improve long-term stability. For example, the effective area of ​​the electrode can be increased by depositing nano-clustered platinum, nanoporous gold, carbon nanotubes and other materials on the electrode surface. The above treatment methods mainly increase the surface roughness of the electrode to anchor the deposited modified material, but delamination may occur after bidirectional current pulse testing or steam sterilization. After searching the prior art, it was found that in 2018, M. Ganji et al. of the University of California, San Diego, USA, wrote an article in Advanced healthcare materials, 2018, 7 (22): 1800923, "Monolithic and scalable Au nanorod substrates improve PEDOT–Metal adhesion and stability in neural electrodes", proposing a gold nanorod substrate, the surface of the gold nanorod-shaped electrode has a uniformly distributed microscopic nanomorphology, which is a gold nanorod layer formed by the dealloying element corrosion method on the basis of a general gold electrode, which is used to improve the bonding force and stability between the modified material PEDOT:PSS and the metal. After 10,000 CV cycles in PBS solution, the spin-coated PEDOT:PSS did not delaminate and the electrochemical impedance did not change significantly, but the PEDOT:PSS on the ordinary planar gold substrate delaminated in less than 1,000 cycles. However, the dealloying element corrosion method requires multi-metal co-sputtering during the metal layer film formation process, and chemical corrosion of one of the metals, such as silver (Ag), may affect the bonding ability between another metal, such as gold (Au), and the flexible substrate, and the co-sputtering process of the two metals is also a cross-contamination of the target material itself.

[0005] Another method is to obtain an intermediate functionalized monolayer or organic molecules through chemical treatment to form covalent bonds at the electrode interface, but the cyclic voltammetric stability test is poor and the impedance will increase. In 2016, C. Boehler et al. from the University of Freiburg in Germany wrote an article titled “Long-term stable adhesion for conducting polymers in biomedical applications: IrOx and nanostructured platinum solve the chronic challenge” in ACS applied materials & interfaces, 2016, 9(1): 189-197. They first sputtered a layer of iridium oxide (SIROF) on the surface of a metal electrode with a diameter of 500 μm as a bonding promotion layer, and then electrodeposited PEDOT:PSS to obtain a good bonding effect. However, whether it is suitable for smaller microelectrode points such as 10 to 20 μm still needs further verification. In 2021, M. Yang et al. from Huazhong University of Science and Technology wrote an article titled “Poly (5-nitroindole) Thin Film as Conductive and Adhesive Interfacial Layer for Robust Neural Networks” in Advanced Functional Materials, 2021, 31(49): 2105857. Interface", and in the applied invention patent CN113368390A "Preparation of conductive adhesion layer of polyindole derivatives for neural electrode modification", a polymer poly (5-nitroindole) PIN-5NO2 with good conductivity, adhesion and biocompatibility is introduced. During the electropolymerization process, the amino group formed by the reduction of the nitro group in 5-nitroindole can form a strong adhesion with the gold (Au) electrode substrate through electrografting. However, the formation process of the polymer adhesion layer is complicated and a variety of chemical reagents are introduced and used, and the potential adverse effects are unknown.

[0006] In previous work, a significant surface micro-wrinkle structure has been obtained by mixing and extracting silicone oil in an elastic polymer substrate and then depositing a poly(p-xylene) film on the elastic polymer substrate. This method significantly enhances the wrinkle amplitude and pattern density, increases the specific surface area, and is applied to flexible neural electrodes for collecting EEG signals in the cerebral cortex. In 2020, a related work was published in Journal of Micromechanics and Microengineering 30(10),104001, entitled "Micro-wrinkle strategy for stable soft neural interface with optimized electroplated PEDOT:PSS", which studied the effect of electroplating time parameters on the electrochemical properties and stability of PEDOT:PSS coatings. The electrode point diameter reported in this work reached 200 microns. As the electrode point diameter decreased, the effect of micro-wrinkles on the specific surface area of ​​the electrode point gradually weakened, and it became unknown whether the coating could be reliably maintained on the electrode point surface for a long time.

[0007] In summary, it is relatively simpler and more reliable to increase the effective surface area of ​​electrode points to ensure that the electrode has stable electrochemical properties. However, the currently reported technical methods for increasing the effective surface area of ​​electrode points still have many problems and defects. Summary of the invention

[0008] In order to overcome the shortcomings of the prior art, the present invention provides a soft neural electrode based on a composite interface of micro-wrinkles and micro-pores and a preparation method thereof, which is composed of a soft base layer, a flexible substrate layer, a conductive metal layer, a flexible packaging layer and a modified coating layer. The microelectrode points exposed by the openings of the flexible packaging layer are a composite interface composed of a micro-wrinkle structure and a micro-pore structure. The preparation method includes: 1. Spin coating and curing of a soft silicone material mixed with silicone oil, and then soaking in an organic solvent to complete the silicone oil extraction to form a soft base layer; 2. Depositing a layer of polymer film on the surface as a flexible substrate layer to automatically form a micro-wrinkle structure; 3. Using a laser cutting process to form a microporous structure on the surface of the flexible substrate layer; 4. Using deposition, photolithography, and etching processes to sequentially form a conductive metal layer and a flexible packaging layer; 5. Using an electrochemical workstation to complete the deposition of the modified coating of the microelectrode point. The present invention can effectively improve the long-term stability of the modified coating material on the surface of the microelectrode point.

[0009] The technical solution adopted by the present invention to solve the technical problem includes the following steps:

[0010] A soft neural electrode based on a micro-wrinkle and micro-porous composite interface, comprising a soft base layer, a flexible substrate layer, a conductive metal layer, a flexible packaging layer and a modified plating layer;

[0011] The soft base layer is located at the bottom of the electrode, the lower surface of the flexible base layer is in contact with the soft base layer, and the upper and lower surfaces of the flexible base layer both present micro-wrinkled structures with regular morphology;

[0012] The upper surface of the flexible substrate layer is provided with a plurality of micro-electrode point areas, and a plurality of evenly distributed blind holes are opened in the micro-electrode point areas to form a micro-pore structure;

[0013] The conductive metal layer covers the flexible substrate layer and includes microelectrode points arranged in the microelectrode point area and extendable wires connected to the microelectrode points;

[0014] The modified plating layer is electroplated on the upper surface of the micro-electrode point.

[0015] Preferably, the soft base layer is polydimethylsiloxane (PDMS) or platinum-catalyzed silicone rubber (Ecoflex or Dragonskin), and has a thickness of 50 to 100 microns.

[0016] Preferably, the material of the flexible substrate layer and the flexible packaging layer is polyparaxylene Parylene-C, the thickness of the flexible substrate layer is 5 to 15 microns, and the thickness of the flexible packaging layer is 1 to 3 microns; the material of the conductive metal layer is gold or platinum or platinum-iridium alloy, and the thickness is 200 to 500 microns.

[0017] Preferably, the material of the modified coating is polystyrene sulfonate PEDOT:PSS.

[0018] Preferably, the wavelength range of the micro-corrugated structure is 5 to 50 microns, the diameter range of the blind hole is 2 to 30 microns, and the diameter range of the micro-electrode point is 20 to 200 microns.

[0019] A method for preparing a soft neural electrode based on a micro-wrinkle and micro-porous composite interface comprises the following steps:

[0020] Step 1: Deposit a layer of aluminum on the surface of the silicon wafer as a sacrificial layer;

[0021] Step 2: Spin-coat polydimethylsiloxane (PDMS) and silicone oil in a set ratio on a silicon wafer and solidify it, then immerse it in an organic solvent to extract the silicone oil, thus forming a soft base layer;

[0022] Step 3: Depositing a first layer of poly(para-xylene) Parylene-C as a flexible substrate layer on the surface of the soft substrate layer by a chemical vapor deposition (CVD) method, the upper and lower surfaces of the flexible substrate layer form a micro-wrinkle structure with a regular morphology due to stress release;

[0023] Step 4: setting a plurality of micro-electrode point areas on the upper surface of the flexible substrate layer, and forming a plurality of evenly distributed blind holes in the micro-electrode point areas by laser cutting technology to form a micro-hole structure;

[0024] Step 5: depositing a layer of chromium and a layer of gold on the upper surface of the flexible substrate layer by sputtering or thermal evaporation process, then spin-coating a positive photoresist, performing pre-baking and photolithography, and then obtaining a patterned conductive metal layer by dry etching; the conductive metal layer includes micro-electrode points arranged in the micro-electrode point area and a ductile wire connected to the micro-electrode points;

[0025] Step 6: Deposit a second layer of Parylene-C as a flexible encapsulation layer by chemical vapor deposition (CVD), then spin-coat a positive photoresist, perform pre-baking and photolithography, and place the device in an oxygen plasma etcher to simultaneously etch the first and second Parylene-C layers in the micro-electrode point area to expose the micro-electrode points;

[0026] Step 7: Soak the whole obtained in step 6 in dilute hydrochloric acid to release the soft neural electrode from the silicon wafer;

[0027] Step 8: Use an electrochemical workstation to electroplate a conductive polymer PEDOT:PSS on the surface of the microelectrode point as a modified coating.

[0028] Preferably, the method for obtaining the microporous structure in step 4 is: obtaining a microporous mask by photolithography, and then obtaining a depth-controllable and non-penetrating microporous structure on the flexible substrate layer with a micro-wrinkled structure by controlling the oxygen plasma etching power and time.

[0029] Preferably, after the step 5 is completed, physical treatment is performed on the surface of the micro-electrode point to form metal-etched micro-nano holes, and then step 6 is performed, which is specifically as follows:

[0030] Place the product obtained in step 5 into a reactive ion etcher with the microelectrode point facing upward and perform etching in an argon atmosphere. When the microelectrode point begins to react, the etching is stopped. At this time, metal etched micro-nanopores are formed along the micro-wrinkle structure and micro-pore structure on the surface of the microelectrode point.

[0031] Preferably, after the step 5 is completed, chemical treatment is performed on the surface of the micro-electrode point to form metal-etched micro-nano holes, and then step 6 is performed, which is specifically as follows:

[0032] When gold is used as the conductive metal layer, the product obtained in step 5 is immersed in a gold etching solution composed of iodine, potassium iodide and water. When the microelectrode points begin to react, they are taken out and cleaned. At this time, metal etching micro-nanopores are formed on the surface of the microelectrode points along the micro-wrinkle structure and micro-pore structure.

[0033] Preferably, in step 8, when the conductive polymer PEDOT:PSS is electroplated on the surface of the microelectrode point using an electrochemical workstation, the thickness of the modified coating is increased by increasing the electroplating time or current intensity until the microporous structure is filled.

[0034] The beneficial effects of the present invention are as follows:

[0035] From the perspective of process preparation, the present invention proposes how to form a controllable micro-nano morphology on the soft neural electrode interface, aiming to combine the dual advantages of micron-scale wrinkles and small holes, improve the specific surface area and roughness of microelectrode points, and form anchor points through micropores. It can effectively improve the long-term stability of modified coating materials such as conductive polymer PEDOT:PSS at the electrode interface, and provide a powerful tool for the in vivo, long-term, stable and high-quality collection of neural signals by soft neural electrodes. It is of great value for the development of the next generation of implantable brain-computer interface core basic devices with excellent electrochemical stability. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] Figure 1 It is a schematic diagram of the two-dimensional structure of the microelectrode point of the soft neural electrode with a composite interface of microfolds and micropores of the present invention.

[0037] Figure 2 The present invention is a process flow chart for preparing a soft neural electrode having a composite interface of micro-wrinkles and micro-pores.

[0038] Figure 3 It is a schematic diagram of the overall three-dimensional structure of the soft neural electrode of the present invention and the microelectrode point with a composite interface of microfolds and micropores.

[0039] Figure 4 This is a schematic diagram of the two-dimensional structure of the soft neural microelectrode point in an embodiment of the present invention, in which the electroplating time is increased so that the plated layer completely fills the interface microporous structure.

[0040] Figure 5 This is a schematic diagram of the two-dimensional structure of soft neural microelectrode points with micro-nano pores formed by gold etching and completely filled with electrochemically modified materials according to an embodiment of the present invention.

[0041] Figure numerals: soft base layer 1, flexible substrate layer 2, conductive metal layer 3, flexible packaging layer 4, modified coating 5, micro-corrugated structure 6, microporous structure 7, stretchable wire 8, micro-electrode point 9, microporous modified coating filled with micropores 10, metal etched micro-nanopores 11. DETAILED DESCRIPTION

[0042] The present invention is further described below in conjunction with the accompanying drawings and embodiments.

[0043] In view of the defects in the prior art, the present invention provides a soft neural electrode based on a composite interface of micro-wrinkles and micropores and a preparation method thereof, in order to effectively solve the problems that the modified coating represented by PEDOT:PSS lacks strong covalent bonds after electroplating on the exposed part of the conductive metal layer, i.e., the surface of the microelectrode point, and that it will expand and shrink in volume when used in a physiological environment, resulting in poor bonding with the metal microelectrode substrate, weak mechanical stability, and low long-term reliability. A new interface construction method is provided, which integrates the dual advantages of the micro-wrinkle structure and the micropore structure, effectively increases the specific surface area, and the modified coating has good anchoring ability in the micropores, which can further improve the long-term stability of the modified coating.

[0044] A soft neural electrode based on a micro-wrinkle and micro-porous composite interface, comprising a soft base layer 1, a flexible substrate layer 2, a conductive metal layer 3, a flexible packaging layer 4 and a modified plating layer 5;

[0045] The soft base layer 1 is located at the bottom of the electrode, the lower surface of the flexible substrate layer 2 is in contact with the soft base layer 1, and the upper and lower surfaces of the flexible substrate layer 2 both present micro-wrinkle structures 6 with regular morphology;

[0046] The upper surface of the flexible substrate layer 2 is provided with a plurality of micro-electrode point areas, and a plurality of evenly distributed blind holes are opened in the micro-electrode point areas to form a micro-pore structure 7;

[0047] The conductive metal layer 3 covers the flexible substrate layer 2, and includes micro-electrode points 9 arranged in the micro-electrode point area and an extendable wire 8 connected to the micro-electrode points 9;

[0048] The modified plating layer 5 is electroplated on the upper surface of the micro-electrode point 9 .

[0049] Preferably, the soft base layer 1 is polydimethylsiloxane (PDMS) or platinum-catalyzed silicone rubber (Ecoflex or Dragonskin), and has a thickness of 50 to 100 microns.

[0050] Preferably, the material of the flexible substrate layer 2 and the flexible packaging layer 4 is polyparaxylene Parylene-C, the thickness of the flexible substrate layer 2 is 5 to 15 microns, and the thickness of the flexible packaging layer 4 is 1 to 3 microns; the material of the conductive metal layer 3 is gold or platinum or platinum-iridium alloy, and the thickness is 200 to 500 microns.

[0051] Preferably, the material of the modified coating layer 5 is polystyrene sulfonate PEDOT:PSS.

[0052] Preferably, the wavelength range of the micro-corrugated structure 6 is 5 to 50 microns, the diameter range of the blind hole is 2 to 30 microns; the diameter size range of the micro-electrode point 9 is 20 to 200 microns, which can be suitable for different types of soft neural electrodes that penetrate deep into brain tissue or adhere to the surface of the cerebral cortex.

[0053] A method for preparing a soft neural electrode based on a micro-wrinkle and micro-porous composite interface comprises the following steps:

[0054] Step 1: Deposit a layer of aluminum on the surface of the silicon wafer as a sacrificial layer;

[0055] Step 2: Spin-coat and solidify polydimethylsiloxane (PDMS) mixed with silicone oil in a set ratio on a silicon wafer, and then immerse the wafer in an organic solvent to extract the silicone oil, thereby forming a soft base layer 1;

[0056] Step 3: depositing a first layer of polyparaxylene Parylene-C as a flexible substrate layer 2 on the surface of the soft substrate layer 1 by a chemical vapor deposition (CVD) method, and the upper and lower surfaces of the flexible substrate layer 2 form a micro-wrinkle structure 6 with a regular morphology due to stress release;

[0057] Step 4: setting a plurality of micro-electrode point areas on the upper surface of the flexible substrate layer 2, and forming a plurality of evenly distributed blind holes in the micro-electrode point areas by laser cutting technology to form a micro-pore structure 7;

[0058] Step 5: depositing a layer of chromium and a layer of gold on the upper surface of the flexible substrate layer 2 by sputtering or thermal evaporation process, then spin coating a positive photoresist, performing pre-baking and photolithography, and then obtaining a patterned conductive metal layer 3 by dry etching; the conductive metal layer 3 includes micro-electrode points 9 arranged in the micro-electrode point area and an extendable wire 8 connected to the micro-electrode points;

[0059] Step 6: Deposit a second layer of polyparaxylene Parylene-C by chemical vapor deposition (CVD) as the flexible encapsulation layer 4, then spin-coat a positive photoresist, perform pre-baking and photolithography, and place the first and second layers of Parylene-C in the micro-electrode point area in an oxygen plasma etcher to simultaneously etch, exposing the micro-electrode point 9, which is a composite interface composed of a micro-wrinkle structure and a micro-porous structure;

[0060] Step 7: Soak the whole obtained in step 6 in dilute hydrochloric acid to release the soft neural electrode from the silicon wafer;

[0061] Step 8: Use an electrochemical workstation to electroplate a conductive polymer PEDOT:PSS on the surface of the microelectrode point 9 as a modified coating 5; the modified coating is deposited on the exposed surface of the microelectrode point, completely and conformally covering the micro-wrinkle structure and the microporous structure. As the deposition time increases, the modified coating material will fill the micropores.

[0062] Preferably, the method for obtaining the microporous structure in step 4 is: obtaining a microporous mask by photolithography, and then obtaining a depth-controllable and non-penetrating microporous structure on the flexible substrate layer with a micro-wrinkled structure by controlling the oxygen plasma etching power and time.

[0063] Preferably, after the step 5 is completed, physical treatment is performed on the surface of the micro-electrode point 9 to form metal-etched micro-nano holes, and then step 6 is performed, which is specifically as follows:

[0064] Place the product obtained in step 5 into a reactive ion etcher with the microelectrode point 9 facing upwards, and perform etching in an argon atmosphere. When the microelectrode point 9 begins to react, the etching is stopped. At this time, metal etching micro-nanopores are formed on the surface of the microelectrode point 9 along the micro-wrinkle structure 6 and the microporous structure 7, which is more conducive to the long-term and stable anchoring of the modified coating on the microelectrode point.

[0065] Preferably, after the step 5 is completed, chemical treatment is performed on the surface of the micro-electrode point 9 to form metal-etched micro-nano holes, and then step 6 is performed, which is specifically as follows:

[0066] When gold is used for the conductive metal layer 3, the product obtained in step 5 is immersed in a gold etching solution composed of iodine, potassium iodide and water. When the microelectrode point 9 begins to react, it is taken out and cleaned. At this time, metal etching micro-nanopores are formed on the surface of the microelectrode point 9 along the micro-wrinkle structure 6 and the micro-pore structure 7.

[0067] Preferably, in step 8, when the conductive polymer PEDOT:PSS is electroplated on the surface of the micro-electrode point 9 using an electrochemical workstation, the thickness of the modified coating 5 is increased by increasing the electroplating time or current intensity until the microporous structure is filled.

[0068] Preferably, the conductive metal layer 3 and the flexible packaging layer 4 may be prepared first, and then a local microporous structure may be formed at the exposed microelectrode point positions by a laser cutting process. Specific embodiment:

[0070] Embodiment 1:

[0071] like Figure 1 As shown, this embodiment provides a schematic diagram of the two-dimensional structure of a microelectrode point of a soft neural electrode with a composite interface of microfolds and micropores, which is composed of five parts from bottom to top: a soft base layer 1, a flexible substrate layer 2, a conductive metal layer 3, a flexible packaging layer 4, and a modified coating layer 5. The surface of the microelectrode point exposed by the opening of the flexible packaging layer is a composite interface composed of a microfold structure 6 and a micropore structure 7.

[0072] Among them, the soft base layer material is polydimethylsiloxane (PDMS) or platinum-catalyzed silicone rubber (such as Ecoflex, Dragonskin, etc.), and the spin coating curing thickness is determined according to actual needs. For example, the thickness of the soft neural electrode used to penetrate deep into the brain tissue can be processed to 50 to 100 microns to effectively reduce the size of the brain tissue wound caused by implantation.

[0073] The flexible substrate layer and the flexible encapsulation layer are made of polyparaxylene, which makes full use of its advantages such as room temperature deposition without introducing additional thermal stress, dense deposited thin film without pinholes, and biocompatibility in line with ISO 10993 medical device certification. The thickness of the flexible substrate layer is 5 to 15 microns, and the thickness of the flexible encapsulation layer is 1 to 3 microns, ensuring that the ultrafast femtosecond laser will not cut through the flexible substrate layer during the subsequent formation of the microporous structure on the flexible substrate layer.

[0074] The conductive metal layer is made of inert precious metals with good biocompatibility, such as gold (Au), platinum (Pt), platinum-iridium alloy (Pt-Ir), etc., and has a thickness of 200 to 500 microns.

[0075] The modified coating uses a conductive polymer material, polystyrene sulfonate (PEDOT:PSS), which has good biocompatibility and can effectively reduce surface impedance and improve the quality of collected signals. The surface of the microelectrode points is covered by an electrochemical plating method.

[0076] The wavelength of the micro-wrinkle structure can be adjusted by process parameters, ranging from 5 to 50 microns; the diameter of the micro-pore structure can be adjusted by ultrafast femtosecond laser processing parameters, ranging from 2 to 30 microns.

[0077] like Figure 2 (a)-(g) show the preparation method of the soft neural electrode with micro-wrinkles and micro-pore composite interface, which is prepared according to the following steps:

[0078] 1) If Figure 2 As shown in (a), a layer of aluminum (Al) with a thickness of 300 nanometers is deposited on the surface of the silicon wafer as a sacrificial layer;

[0079] 2) If Figure 2 As shown in (b), PDMS is mixed with silicone oil, spin-coated on a silicon wafer, and heated and cured. The silicone oil in the PDMS is extracted by immersing the PDMS in an organic solvent such as chloroform to form a soft base layer.

[0080] 3) If Figure 2 As shown in (c), a layer of Parylene-C with a thickness of 10 microns is deposited on the PDMS surface by chemical vapor deposition (CVD) as a flexible substrate layer. Due to stress release, a micro-wrinkle structure with regular morphology is formed on the interface;

[0081] 4) If Figure 2 As shown in (d), an ultrafast femtosecond laser cutting machine is used to form a uniformly distributed microporous structure with a cutting depth of about 1 / 2 of the thickness of the flexible substrate layer on the surface of the flexible substrate layer;

[0082] 5) If Figure 2As shown in (e), a layer of chromium and a layer of gold are sequentially deposited on the surface of the flexible substrate layer by sputtering or thermal evaporation process, the thickness of chromium and gold are 30 nanometers and 300 nanometers respectively, and then a positive photoresist with a thickness of 3 micrometers is spin-coated, pre-baking and photolithography are performed, and then a patterned conductive metal layer is obtained by dry etching;

[0083] 6) If Figure 2 As shown in (f), a second layer of Parylene-C with a thickness of 1 micron is deposited by chemical vapor deposition (CVD) as a flexible encapsulation layer, followed by spin coating of a 15 micron thick positive photoresist, pre-baking, photolithography, and placing in an oxygen plasma etcher to simultaneously etch two layers of Parylene-C to expose the microelectrode points and form the outer contours of the flexible substrate layer and the flexible encapsulation layer, and finally soaking in dilute hydrochloric acid for 6 hours to release the soft neural electrodes from the silicon wafer;

[0084] 7) If Figure 2 As shown in (g), a conductive polymer PEDOT:PSS is electroplated on the surface of the microelectrode point using an electrochemical workstation as a modified coating.

[0085] like Figure 3 As shown in the figure, a schematic diagram of the overall three-dimensional structure of a soft neural electrode that can penetrate brain tissue is given. The electrode body includes a soft base layer 1, a stretchable wire 8 and a microelectrode point 9, wherein the stretchable wire is composed of a flexible substrate layer, a conductive metal layer, and a flexible packaging layer, mainly to cooperate with the soft base layer below to give the electrode the ability to stretch and deform. The local enlarged image shows that the microelectrode point is composed of a composite interface including a micro-wrinkle structure 6 and a microporous structure 7. The diameter, spacing and number of the microporous structure can be drilled on demand by an ultrafast femtosecond laser. Figure 3 Taking the medium-soft neural electrode as an example, if the diameter of the microelectrode point is 50 microns, the wavelength of the micro-wrinkle structure is 10 microns, and the diameter of the micropore structure is 5 microns, it can ensure that the microelectrode point composite interface has a significant specific surface area and a sufficient number of anchor points, which is beneficial to ensure the anchoring and binding ability of the modified coating PEDOT:PSS.

[0086] Example 2

[0087] The present embodiment provides a method for preparing a soft neural electrode based on a composite interface of micro-wrinkles and micropores. The specific implementation steps are the same as those in Example 1, except that in the step of electroplating the conductive polymer PEDOT:PSS on the surface of the microelectrode point, the thickness of the modified coating can be increased by increasing the electroplating time or the current intensity until the microporous structure is filled, forming a structure similar to a mortise and tenon joint, which can more effectively anchor the modified coating on the surface of the microelectrode point and improve the tolerance to working conditions such as stimulation current, body fluid immersion, and physical friction. The modified coating 10 filled with micropores also acts as a "water reservoir". When the microelectrode point works in the body for a long time and the coating is partially peeled off or falls off, a certain volume of modified material still exists in the micropores, which can continue to function and extend the working life of the electrode.

[0088] Example 3

[0089] This embodiment provides a method for preparing a soft neural electrode based on a composite interface of microfolds and micropores. The specific implementation steps are the same as those in Example 1, except that the metal is physically or chemically treated on the microelectrode surface exposed by the conductive metal layer to form metal etched micro-nanopores 11. The treatment methods are exemplified as follows: if a physical treatment method is used, the soft neural electrode can be placed in a reactive ion etcher, with the microelectrode facing upward, and short-term etching is performed in an argon (Ar) atmosphere. Since the reaction rate of the polymer film and silicone material is much lower than the metal etching rate, the soft substrate layer or the flexible packaging layer will hardly be affected. When the exposed metal microelectrode begins to react, the etching can be stopped. At this time, it can be observed that metal etching micro-nano holes are formed on the surface of the microelectrode along the micro-wrinkle structure and the micro-porous structure surface; if a chemical treatment method is used, when gold (Au) is used as the conductive metal layer, all microelectrode points can be immersed in a gold etching solution composed of iodine, potassium iodide and water at the same time. When the diamond begins to react, the electrode can be taken out and cleaned. At this time, significant metal etching micro-nano holes will be generated on the surface of the microelectrode along the micro-wrinkle structure and the micro-porous structure surface. In addition, other methods other than the above two examples can be used to form metal etching micro-nano holes to improve the interface anchoring strength of the subsequent modified coating on the microelectrode point.

[0090] The preparation method of the soft neural electrode in the present invention can be extended to different types of biological signal sensors, such as measuring neuro-electrophysiological signals such as electroencephalogram, electrocardiogram, electromyography, and electrooculography. It also has the potential to be used as a stimulation electrode for long-term and stable electrical stimulation of neural tissue, and the charge injection capacity of the modified coating will not be significantly reduced.

[0091] The soft neural electrode of the present invention combines the dual advantages of micron-scale wrinkles and small holes, improves the specific surface area and roughness of the microelectrode points, and forms anchor points through micropores, which can effectively improve the long-term stability of the modified coating material on the surface of the microelectrode points, and provide a reliable implantable brain-computer interface front-end tool for brain medical diagnosis, behavioral cognition, precise regulation, etc.

Claims

1. A method for preparing a soft neural electrode based on a composite interface of micro-folds and micro-pores, wherein the soft neural electrode comprises a soft substrate layer, a flexible substrate layer, a conductive metal layer, a flexible packaging layer and a modified coating layer; the soft substrate layer is located at the bottom of the electrode, the lower surface of the flexible substrate layer is in contact with the soft substrate layer, and the upper and lower surfaces of the flexible substrate layer both present a micro-fold structure with a regular morphology; a plurality of micro-electrode point areas are arranged on the upper surface of the flexible substrate layer, and a plurality of evenly distributed blind holes are opened in the micro-electrode point areas to form a micro-pore structure; the conductive metal layer covers the flexible substrate layer, including micro-electrode points arranged in the micro-electrode point areas and an extendable wire connected to the micro-electrode points; the modified coating layer is electroplated on the upper surface of the micro-electrode points, characterized in that The steps include: Step 1: Deposit a layer of aluminum on the surface of the silicon wafer as a sacrificial layer; Step 2: Spin-coat polydimethylsiloxane (PDMS) and silicone oil in a set ratio on a silicon wafer and solidify it, then immerse it in an organic solvent to extract the silicone oil, thus forming a soft base layer; Step 3: Depositing a first layer of poly(para-xylene) Parylene-C as a flexible substrate layer on the surface of the soft substrate layer by a chemical vapor deposition (CVD) method, the upper and lower surfaces of the flexible substrate layer form a micro-wrinkle structure with a regular morphology due to stress release; Step 4: setting a plurality of micro-electrode point areas on the upper surface of the flexible substrate layer, and forming a plurality of evenly distributed blind holes in the micro-electrode point areas by laser cutting technology to form a micro-hole structure; Step 5: depositing a layer of chromium and a layer of gold on the upper surface of the flexible substrate layer by sputtering or thermal evaporation process, then spin coating a positive photoresist, performing pre-baking and photolithography, and then obtaining a patterned conductive metal layer by dry etching; The conductive metal layer includes microelectrode points arranged in the microelectrode point area and an extendable wire connected to the microelectrode points; Step 6: Deposit a second layer of Parylene-C as a flexible encapsulation layer by chemical vapor deposition (CVD), then spin-coat a positive photoresist, perform pre-baking and photolithography, and place the device in an oxygen plasma etcher to simultaneously etch the first and second Parylene-C layers in the micro-electrode point area to expose the micro-electrode points; Step 7: Soak the whole obtained in step 6 in dilute hydrochloric acid to release the soft neural electrode from the silicon wafer; Step 8: Use an electrochemical workstation to electroplate a conductive polymer PEDOT:PSS on the surface of the microelectrode point as a modified coating.

2. The method for preparing a soft neural electrode based on a micro-wrinkle and micro-porous composite interface according to claim 1, characterized in that: The soft base layer is polydimethylsiloxane (PDMS) or platinum-catalyzed silicone rubber (Ecoflex or Dragonskin), and has a thickness of 50 to 100 microns.

3. The method for preparing a soft neural electrode based on a composite interface of micro-wrinkles and micro-pores according to claim 1, characterized in that: The material of the flexible substrate layer and the flexible packaging layer is polyparaxylene Parylene-C, the thickness of the flexible substrate layer is 5-15 microns, and the thickness of the flexible packaging layer is 1-3 microns; the material of the conductive metal layer is gold or platinum or platinum-iridium alloy, and the thickness is 200-500 microns.

4. The method for preparing a soft neural electrode based on a composite interface of micro-wrinkles and micro-pores according to claim 1, characterized in that: The material of the modified coating is polystyrene sulfonate PEDOT:PSS.

5. The method for preparing a soft neural electrode based on a composite interface of micro-wrinkles and micro-pores according to claim 1, characterized in that: The wavelength range of the micro-fold structure is 5-50 microns, the diameter range of the blind hole is 2-30 microns, and the diameter size range of the micro-electrode point is 20-200 microns.

6. The method for preparing a soft neural electrode based on a micro-wrinkle and micro-porous composite interface according to claim 1, characterized in that: The method for obtaining the microporous structure in step 4 is: obtaining a microporous mask by photolithography, and then obtaining a depth-controllable and non-penetrating microporous structure on the flexible substrate layer with a micro-wrinkled structure by controlling the oxygen plasma etching power and time.

7. The method for preparing a soft neural electrode based on a composite interface of micro-wrinkles and micro-pores according to claim 1, characterized in that: After step 5 is completed, physical treatment is performed on the surface of the microelectrode point to form metal-etched micro-nano holes, and then step 6 is performed, which is specifically as follows: Place the product obtained in step 5 into a reactive ion etcher with the microelectrode point facing upward and perform etching in an argon atmosphere. When the microelectrode point begins to react, the etching is stopped. At this time, metal etched micro-nanopores are formed along the micro-wrinkle structure and micro-pore structure on the surface of the microelectrode point.

8. The method for preparing a soft neural electrode based on a composite interface of micro-wrinkles and micro-pores according to claim 1, characterized in that: After step 5 is completed, chemical treatment is performed on the surface of the micro-electrode point to form metal-etched micro-nano holes, and then step 6 is performed, which is specifically as follows: When gold is used as the conductive metal layer, the product obtained in step 5 is immersed in a gold etching solution composed of iodine, potassium iodide and water. When the microelectrode points begin to react, they are taken out and cleaned. At this time, metal etching micro-nanopores are formed on the surface of the microelectrode points along the micro-wrinkle structure and micro-pore structure.

9. The method for preparing a soft neural electrode based on a composite interface of micro-wrinkles and micro-pores according to claim 1, characterized in that: In step 8, when the conductive polymer PEDOT:PSS is electroplated on the surface of the microelectrode point using an electrochemical workstation, the thickness of the modified coating is increased by increasing the electroplating time or current intensity until the microporous structure is filled.

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