A preparation method of a hydrogel-based high-density flexible electrode array film based on photoetching transfer and frozen nanomachining technology

Abstract

The application discloses a preparation method of a hydrogel-based high-density flexible electrode array film based on photoetching transfer and frozen nanometric cutting technology. Firstly, a photoetching master is used to limit the planar pattern and microstructure size of electrode sites, conductive interconnections and connection ends. Then, a filling structure with flexible support and electrical insulation is formed by PDMS replication, a conductive polymer hydrogel precursor is filled into the structure and in-situ gelled, so that the conductive hydrogel pattern and the PDMS form an integrated composite. Then, the composite is rapidly cooled by low-temperature isopentane, and overall ultrathin cutting is carried out in a constant-temperature freezing cavity by using a diamond knife, so that an electrode array film with thickness controlled by feed amount and maintaining array pattern is obtained. The process flow has the advantages of reusable template, designable array parameters, adjustable thickness, controllable processing, high device integration potential and the like, and can provide a new technical route for large-scale and standardized preparation of high-density brain-computer interface electrode arrays.

Description

Technical Field

[0001] This invention belongs to the field of flexible electronics, bioelectrodes and conductive polymer hydrogel micro / nano manufacturing technology, and relates to a method for preparing flexible electrode array films. Specifically, it relates to a method for preparing ultrathin high-density electrode array films by photolithographic template transfer, PDMS soft elastic structure replication, in-situ in-situ infusion and curing of conductive polymer hydrogel, and low-temperature cryogenic nano-cutting. Background Technology

[0002] Cortical surface electrodes in brain-computer interfaces need to minimize bending stiffness while maintaining electrical performance to adapt to the working environment of soft, complexly curved, and continuously micro-moving brain tissue. Traditional metal thin-film electrodes typically rely on polyimide, parylene, or other polymer substrates. Although they can achieve micro-patterning, there is still a modulus difference between the metal and soft tissue. During long-term contact, the device may experience interface slippage, local stress concentration, and changes in electrode impedance.

[0003] Conductive polymer hydrogels combine the high water content, flexibility, and biocompatibility of hydrogels with the electron / ion transport capabilities of conductive polymers, demonstrating significant application potential in neural electrodes, flexible sensors, and bioelectronic interfaces. Compared to traditional rigid electrodes, conductive polymer hydrogels can better mimic the mechanical environment of biological tissues, reduce the modulus difference at the tissue-device interface, and synergistically improve electrode interface properties through wet ion transport and electron transport. However, existing hydrogel microelectrodes are typically fabricated using direct photolithography, printing, molding, or coating. For array devices with further reduced thickness, these methods may face challenges related to pattern integrity, thickness uniformity, demolding and transfer, mass production, and mechanical manipulation. Therefore, a fabrication route that can simultaneously maintain array patterning, composite interfaces, and film continuity is needed. Summary of the Invention

[0004] To address the challenges of precisely controlling the thickness of ultrathin hydrogel electrode arrays, the difficulty in completely transferring array patterns, and the tendency of composite materials to crack or delaminate during low-temperature cutting, this invention provides a method for preparing hydrogel-based high-density flexible electrode array films based on photolithography transfer and cryogenic nano-cutting technology. These electrode array films can be used in brain-computer interfaces, neural signal acquisition, and adhesive flexible bioelectronic devices.

[0005] The objective of this invention is achieved through the following technical solution:

[0006] A method for preparing a hydrogel-based high-density flexible electrode array film based on photolithography transfer and cryogenic nano-cutting technology includes the following steps:

[0007] Step 1, Master mold preparation:

[0008] Step 1-1: Clean the silicon wafer and perform dehydration and baking;

[0009] Steps 1-2: Spin-coat photoresist on the silicon wafer surface, and form a transfer master mold through pre-baking, mask exposure, post-baking and development. The mask pattern includes multiple electrode sites with a diameter of 20~120μm and a microstructure height of 10~80μm.

[0010] Steps 1-3: Apply fluorosilane anti-stick treatment to the surface of the master mold;

[0011] Step 2, PDMS copy:

[0012] Step 2-1: Mix the PDMS prepolymer with the curing agent and degas under vacuum, pour it onto the transfer master mold, and cure it in an oven. Control the curing temperature to be 80~100℃ and the time to be 1~3 hours.

[0013] Step 2-2: After curing, demold to obtain a PDMS elastic matrix with an electrode array-shaped infused microstructure;

[0014] Steps 2-3: Based on connection and packaging requirements, reserve positioning holes, lead-out slots, or cut reference edges on the PDMS elastic substrate;

[0015] Step 3, Precursor Infusion:

[0016] Step 3-1: Perform oxygen plasma treatment on the PDMS-infused microstructures, controlling the power to be 50~100W and the treatment time to be 10~60s;

[0017] Step 3-2: Fill the microstructure with precursor by vacuum-assisted infusion and scrape off excess precursor from the PDMS surface;

[0018] Step 4, In-situ gelation:

[0019] Step 4-1: The precursor is polymerized into a gel within the infused microstructure using a redox initiation method;

[0020] Step 4-2: After gelation, wash thoroughly with deionized water or physiological buffer to remove unreacted monomers, thereby forming an integrated electrode array composite with PDMS surrounding the conductive polymer hydrogel pattern.

[0021] Step 5, Freeze Protection and Rapid Cooling:

[0022] Step 5-1: Based on the requirements for hydrogel water content and slice integrity, place the electrode array composite in an OCT cryoprotectant solution for treatment;

[0023] Step 5-2: Pre-cool isopentane to -160℃, then immerse the composite in isopentane for 30~60 seconds to allow the composite to quickly pass through the water phase crystallization temperature range.

[0024] Step 5-3: After rapid cooling, maintain the low temperature and transfer to a cryo-slicing device;

[0025] Step 6, trimming and ultra-thin cutting:

[0026] Step 6-1: Fix the composite onto the sample holder of the cryosectioning device, ensuring that the cutting direction is aligned with the target film formation direction of the electrode array pattern;

[0027] Step 6-2: Stabilize the constant temperature freezing chamber at -130℃, first use a glass cutter to trim the block, then replace it with a diamond cutter, set the cutting thickness, cutting speed and cutter angle and then cut to obtain a continuous electrode array film with a thickness of 50~500nm.

[0028] Step 6-3: Use an antistatic device, eyelash pen, film collection ring, or flexible carrier film to complete film collection and transfer;

[0029] Step 7, Post-processing and Connection:

[0030] Step 7-1: Allow the electrode array membrane to rewarm in a controlled humidity or buffer environment;

[0031] Step 7-2: When it is necessary to restrict the exposure of non-electrode areas, an insulating layer is formed on the conductive interconnect, and the electrode sites and connection ends are exposed through a mask, laser windowing or photolithography windowing.

[0032] Compared with the prior art, the present invention has the following advantages:

[0033] 1. This invention predefines the geometry, number of channels, unit size, and array spacing of the electrode array by using a photolithography template and PDMS transfer structure, which can improve the consistency and repeatability of the electrode array structure.

[0034] 2. This invention uses a PDMS soft elastic structure to spatially confine and flexibly support the conductive polymer hydrogel, enabling the hydrogel microelectrode to maintain array integrity during infusion, gelation, freezing, cutting, and transfer, thereby reducing the problems of easy breakage, curling, and difficult handling of ultrathin hydrogel films.

[0035] 3. The present invention uses isopentane pre-cooled with liquid nitrogen to rapidly freeze the composite electrode array block, which can reduce the damage to the gel network and microarray structure caused by the growth of ice crystals inside the hydrogel, and is beneficial to obtaining continuous and complete ultrathin electrode array slices.

[0036] 4. This invention uses a -130℃ constant temperature freezing chamber, a cryo-slicer, and diamond tools for directional cutting, which can achieve precise control of the electrode array film thickness and obtain flexible electrode array films with nanometer or submicron thickness.

[0037] 5. The electrode array film obtained by the present invention combines the softness, wet affinity, biocompatibility and low interfacial impedance of conductive polymer hydrogels with the flexible support and insulating isolation of PDMS structure, making it suitable for brain-computer interface neural signal acquisition, neural electrical stimulation, flexible bioelectrodes and implantable / attached bioelectronic devices.

[0038] 6. The process flow of this invention has the advantages of reusable templates, designable array parameters, adjustable thickness, controllable processing, and high device integration potential, which can provide a new technical route for the large-scale and standardized fabrication of high-density brain-computer interface electrode arrays. Attached Figure Description

[0039] Figure 1 This is a schematic diagram of the master mold preparation process;

[0040] Figure 2 This is a schematic diagram of the PDMS copying process;

[0041] Figure 3 A mirror image of the master mold for photolithography transfer.

[0042] Figure 4 To reproduce the demolded structured light mirror image using PDMS;

[0043] Figure 5 This is a schematic diagram of the precursor infusion process;

[0044] Figure 6 Cross-sectional view of the PDMS / conductive polymer hydrogel electrode array block formed after cross-linking and curing;

[0045] Figure 7 A schematic diagram of cryogenic nano-cutting of a composite electrode array block in a -130℃ constant temperature freezing chamber;

[0046] Figure 8 This is a schematic diagram of the structure of an ultrathin high-density electrode array film;

[0047] Figure 9 This study explores the application of ultrathin, high-density electrode array films in brain-computer interfaces. Detailed Implementation

[0048] The technical solution of the present invention will be further described below with reference to the accompanying drawings, but it is not limited thereto. Any modifications or equivalent substitutions to the technical solution of the present invention that do not depart from the spirit and scope of the technical solution of the present invention should be covered within the protection scope of the present invention.

[0049] This invention provides a method for preparing a hydrogel-based high-density flexible electrode array film based on photolithography transfer and cryogenic nano-cutting technology. First, a photolithography master mold is used to define the planar pattern and microstructure dimensions of electrode sites, conductive interconnects, and connection ends. Then, a PDMS-based infusion structure with both flexible support and electrical insulation is formed. A conductive polymer hydrogel precursor is then infused into this structure and gelled in situ, forming an integrated composite of the conductive hydrogel pattern and PDMS. Next, the composite is rapidly cooled using low-temperature isopentane, and ultra-thin cutting is performed using a diamond blade in a cryogenic chamber, thereby obtaining an electrode array film whose thickness is controlled by the feed rate and maintains the array pattern. The specific steps include the following:

[0050] (1) Preparation of the master mold. For example... Figure 1 As shown, the silicon wafer is cleaned and dehydrated, then baked. Photoresist is spin-coated onto the wafer surface, followed by pre-baking, mask exposure, post-baking, and development to form a transfer master mold. Figure 3 As shown. The mask pattern includes multiple electrode sites with diameters ranging from 20 to 120 μm and microstructure heights ranging from 10 to 80 μm. The surface of the master mold is treated with fluorosilane for anti-sticking.

[0051] (2) PDMS copying. For example... Figure 2 As shown, PDMS prepolymer and curing agent were mixed at a mass ratio of 10:1 and vacuum degassed. The mixture was then poured onto a transfer master mold and cured in an oven at 80°C for 2 hours. After curing, the mold was removed to obtain a PDMS elastic matrix with an electrode array-shaped infused microstructure, as shown. Figure 4 As shown. Depending on the connection and packaging requirements, positioning holes, lead-out slots, or cutting reference edges can be pre-drilled in the PDMS elastic substrate.

[0052] (3) Precursor perfusion. For example... Figure 5 As shown, the PDMS-infused microstructures were subjected to oxygen plasma treatment at a power of 70W for 30 seconds. A hydrogel precursor solution was prepared by mixing AAM (acrylamide) monomer, crosslinking agent MBAA (N,N'-methylenebisacrylamide), initiator APS (ammonium persulfate), and PEDOT:PSS dispersion. The acrylamide content was 5-25% by mass, the crosslinking agent was 0.02-1% by mass of acrylamide, the initiator was 0.5-1% by mass of acrylamide, and the PEDOT:PSS solid content was 0.1-10% of the precursor solution. Vacuum-assisted infusion was used to fill the infused microstructures with the precursor solution, and excess precursor on the PDMS surface was scraped off.

[0053] (4) In-situ gelation. A redox initiation method is used to polymerize the precursor within the perfused microstructure. After gelation, the mixture is thoroughly washed with deionized water or physiological buffer to remove unreacted monomers. This forms an integrated electrode array composite with a conductive polymer hydrogel pattern surrounded by PDMS, such as... Figure 6 As shown.

[0054] (5) Cryoprotection and rapid cooling. Based on the requirements for hydrogel water content and section integrity, the electrode array composite was treated in a cryoprotectant containing OCT. Isopentane was pre-cooled to -160°C, and then the composite was immersed in isopentane for 30 seconds to allow the composite to quickly pass through the water phase's easily crystallizing temperature range. After treatment, it was kept at a low temperature and transferred to a cryosectioning device.

[0055] (6) Block trimming and ultra-thin cutting. For example... Figure 7 As shown, the composite was fixed on the sample holder of a cryo-microtome, with the cutting direction aligned with the target film formation direction of the electrode array pattern. The cryo-chamber was stabilized at -130°C. First, a glass cutter was used to trim the film, then a diamond cutter was used. After setting the cutting thickness, cutting speed, and cutter angle, cutting was performed to obtain a continuous electrode array film with a thickness of 50–500 nm. Figure 8 As shown. Antistatic devices, eyelash pens, film-retrieving rings, or flexible carrier films are used to complete film retrieval and transfer.

[0056] (7) Post-processing and connection. The electrode array film is rewarmed in a controlled humidity or buffer environment. When it is necessary to limit the exposure of non-electrode areas, an insulating layer is formed on the conductive interconnects, and electrode sites and connection terminals are exposed through a mask, laser windowing, or photolithographic windowing. The connection terminals can be electrically connected to flexible printed circuits, anisotropic conductive films, or conductive hydrogel connectors.

Claims

1. A method for preparing a hydrogel-based high-density flexible electrode array thin film based on photolithography transfer and cryogenic nano-cutting technology, characterized in that... The method includes the following steps: Step 1, Master mold preparation: Step 1-1: Clean the silicon wafer and perform dehydration and baking; Steps 1-2: Spin-coat photoresist onto the silicon wafer surface, and form a transfer master mold through pre-baking, mask exposure, post-baking, and development; Steps 1-3: Apply fluorosilane anti-stick treatment to the surface of the master mold; Step 2, PDMS copy: Step 2-1: Mix the PDMS prepolymer with the curing agent and degas under vacuum, pour it onto the transfer master mold, and cure it in an oven; Step 2-2: After curing, demold to obtain a PDMS elastic matrix with an electrode array-shaped infused microstructure; Step 3, Precursor Infusion: Step 3-1: Perform oxygen plasma treatment on the PDMS-infused microstructures; Step 3-2: Fill the microstructure with precursor by vacuum-assisted infusion and scrape off excess precursor from the PDMS surface; Step 4, In-situ gelation: Step 4-1: The precursor is polymerized into a gel within the infused microstructure using a redox initiation method; Step 4-2: After gelation, wash thoroughly with deionized water or physiological buffer to remove unreacted monomers, thereby forming an integrated electrode array composite with PDMS surrounding the conductive polymer hydrogel pattern. Step 5, Freeze Protection and Rapid Cooling: Step 5-1: Based on the requirements for hydrogel water content and slice integrity, place the electrode array composite in an OCT cryoprotectant solution for treatment; Step 5-2: Pre-cool isopentane to -160℃, then immerse the composite in isopentane for 30~60 seconds to allow the composite to quickly pass through the water phase crystallization temperature range. Step 5-3: After rapid cooling, maintain the low temperature and transfer to a cryo-slicing device; Step 6, trimming and ultra-thin cutting: Step 6-1: Fix the composite onto the sample holder of the cryosectioning device, ensuring that the cutting direction is aligned with the target film formation direction of the electrode array pattern; Step 6-2: Stabilize the constant temperature freezing chamber at -130℃, first use a glass cutter to trim the block, then replace it with a diamond cutter, set the cutting thickness, cutting speed and cutter angle and then cut to obtain a continuous electrode array film. Step 6-3: Use an antistatic device, eyelash pen, film collection ring, or flexible carrier film to complete film collection and transfer; Step 7, Post-processing and Connection: Step 7-1: Allow the electrode array membrane to rewarm in a controlled humidity or buffer environment; Step 7-2: When it is necessary to restrict the exposure of non-electrode areas, an insulating layer is formed on the conductive interconnect, and the electrode sites and connection ends are exposed through a mask, laser windowing or photolithography windowing.

2. The method for preparing a hydrogel-based high-density flexible electrode array film based on photolithography transfer and cryogenic nano-cutting technology according to claim 1, characterized in that... In steps 1-2, the mask pattern includes multiple electrode sites.

3. The method for preparing a hydrogel-based high-density flexible electrode array film based on photolithography transfer and cryogenic nano-cutting technology according to claim 2, characterized in that... The diameter of the electrode sites is 20~120μm, and the height of the microstructure is 10~80μm.

4. The method for preparing a hydrogel-based high-density flexible electrode array film based on photolithography transfer and cryogenic nano-cutting technology according to claim 1, characterized in that... In step 2-1, the curing temperature is 80~100℃ and the time is 1~3 hours.

5. The method for preparing a hydrogel-based high-density flexible electrode array film based on photolithography transfer and cryogenic nano-cutting technology according to claim 1, characterized in that... Step 2 also includes steps 2-3: according to connection and packaging requirements, pre-reserving positioning holes, lead-out grooves or cutting reference edges on the PDMS elastic substrate.

6. The method for preparing a hydrogel-based high-density flexible electrode array film based on photolithography transfer and cryogenic nano-cutting technology according to claim 1, characterized in that... In step 3-1, the power of the oxygen plasma treatment is 50~100W, and the treatment time is 10~60s.

7. The method for preparing a hydrogel-based high-density flexible electrode array film based on photolithography transfer and cryogenic nano-cutting technology according to claim 1, characterized in that... In step 3-2, the precursor is prepared into a hydrogel precursor solution by acrylamide monomer, crosslinking agent, initiator and PEDOT:PSS dispersion, wherein: the mass fraction of acrylamide is 5~25%, the amount of crosslinking agent is 0.02~1% of the mass of acrylamide, the amount of initiator is 0.5~1% of the mass of acrylamide, and the solid content of PEDOT:PSS is 0.1~10% of the precursor solution.

8. The method for preparing a hydrogel-based high-density flexible electrode array thin film based on photolithography transfer and cryogenic nano-cutting technology according to claim 7, characterized in that... The crosslinking agent is N,N'-methylenebisacrylamide, and the initiator is ammonium persulfate.

9. The method for preparing a hydrogel-based high-density flexible electrode array film based on photolithography transfer and cryogenic nano-cutting technology according to claim 1, characterized in that... In step 6-2, the thickness of the continuous electrode array film is 50~500nm.

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