An ultra-flexible hydrogel-based optical computer interface device and a preparation method thereof

Abstract

The application discloses a kind of super-flexible hydrogel-based optical computer interface devices and preparation method, including flexible substrate, electrode body, micro LED chip array and interface end.Micro LED chip light emitting work, activate neuron to carry out potential emission, and its transmission is transmitted to interface end by electrode point collection cerebral cortex electric signal.The specific preparation process is as follows: step one, preparation collection electrode and light stimulation electrode using MEMS process;Step two, adjust initiator concentration, crosslinking agent concentration and type, and prepare hydrogel substrate by doping silver nanowire ratio;Step three, interface integration is realized in order by light stimulation electrode transfer printing, liquid hydrogel substrate regulation and collection electrode transfer printing.The device has the ability of brain cortex multi-site light stimulation and synchronous spatial multi-site nerve signal monitoring, by the performance regulation of hydrogel-polymer film photoelectric nerve electrode integrated interface, the device is endowed with super-flexibility and adhesion, can be more closely fitted to cerebral cortex.

Description

TECHNICAL FIELD

[0001] The application belongs to the field of bio-medical electrical technology, and particularly relates to a super-flexible hydrogel-based optical computer interface device and a preparation method. BACKGROUND

[0002] In recent years, optogenetics has brought revolutionary influence to neural circuit research. Compared with electrical stimulation, drug stimulation and other neural regulation methods, optical stimulation has millisecond-level time response accuracy, can selectively regulate specific neurons, and can accurately explore the causal relationship between specific neural circuits and brain functions by forming a closed-loop system combined with electrophysiological recording. In view of the softness of brain tissue, the mechanical matching performance of the device after implantation is prone to deteriorate over time, thereby causing signal artifact problems. The development of a super-flexible hydrogel-based optical computer interface device can effectively solve the above problems.

[0003] In terms of electrophysiological recording function, a planar electrode attached to the cerebral cortex can capture the activity of a large range of shallow neuron groups, i.e., electrocorticography (ECoG), which is crucial for basic brain science and clinical brain disease research. Therefore, it is urgent to develop a brain-computer interface device with multi-site optical stimulation and synchronous spatial multi-site neural signal monitoring function, which has super flexibility and adhesion, and provides a new tool for neuroscience research.

[0004] Through the search of the prior art, it is found that in 2013, Professor Wen Li's team of Michigan State University published an article: "Opto-μECoG array: A Hybrid neural interface with transparent μECoG electrode array and integrated LEDs for optogenetics" (IEEE transactions on biomedical circuits and systems, 2013, 7(5):593-600), which proposes a flexible cortical electroencephalogram acquisition electrode and an integrated 16-micro LED array optical stimulation electrode based on a Parylene substrate. The two are integrated by means of 50-micron-thick epoxy SU-8 glue, and do not have the ability to stretch and deform.

[0005] In 2020, Professor Liu Jingquan's team from Shanghai Jiaotong University published a paper titled "Flexible and stretchable opto-electric neural interface for low-noise electrocorticogram recordings and neuromodulation in vivo" (Biosensors and Bioelectronics, 2020, 153:112009), which proposed a stretchable optoelectronic neural electrode based on polyimide (PI) substrate and Dragonskin silicone substrate. By depositing a layer of Ti / SiO2 material on the back of the PI substrate and using chemical condensation reaction, the 100-micron-thick silicone substrate was bonded. However, there was a phenomenon of wire debonding under large tensile deformation.

[0006] In 2021, Williams et al. published a paper titled "Design and Fabrication of Blue LED-Integrated Graphene Electrodes for Neural Stimulation and Signal Recording", which proposed a flexible cortical electroencephalogram acquisition electrode based on flexible polymer film SU-8 substrate and an optical stimulation electrode integrated with 16 micro-LED arrays. The two were integrated by a 50-micron-thick ultraviolet-curable polyurethane. However, they did not have the ability to stretch and deform. It can be seen that the current optoelectronic integrated brain-computer interface device does not have super flexibility, which is important for improving the biocompatibility of the device and reducing the immune rejection reaction of long-term implantation.

[0007] Tao Hu et al. from the Chinese Academy of Sciences Microsystem Institute disclosed an invention patent CN111973181A, which proposed a cortical electrode integrated with signal acquisition and stimulation functions and its manufacturing method. The electrode includes a light stimulation electrode structure, a thermal stimulation electrode structure, and an acquisition electrode structure, which enables the electrode to have both light and thermal stimulation functions and to acquire and record signals generated by the light and thermal stimulation through the acquisition electrode structure. However, the light stimulation electrode uses a whole piece of PI or SU-8 as the substrate, which has high rigidity after integrating with micro-scale LED lights, making it difficult to closely adhere to the brain cortex tissue with complex surface.

[0008] An invention patent CN112259570A disclosed by Wang Minghao et al. of Hangzhou University of Electronic Science and Technology proposes a flexible brain cortex electrode for neural recording and optical stimulation and a preparation method thereof, which comprises a flexible optical probe array layer, a flexible adhesive layer and a flexible micro LED array layer, and a plurality of micro LED units are arranged on the flexible micro LED array layer; each micro LED unit is aligned with each recording and stimulation unit. The electrode also uses a whole PI as a recording electrode substrate, and combines an LED coupled SU-8 optical waveguide structure to realize neural recording and stimulation, but due to the introduction of the high-rigidity SU-8 optical waveguide probe with a three-dimensional structure, the overall rigidity of the electrode is further increased, which is not conducive to the expansion of the use in large-area complex curved brain areas.

[0009] In summary, there is no optoelectronic integrated brain-computer interface device with super flexibility and adhesion, and capable of realizing multi-site optical stimulation and synchronous electrical recording of the brain cortex in the existing flexible non-embedded brain-computer interface. SUMMARY

[0010] In order to overcome the shortcomings of the prior art, the present application provides a super flexible hydrogel-based optical brain-computer interface device and a preparation method thereof, which comprises a flexible substrate, an electrode body, a micro LED chip array and an interface end. The micro LED chip emits light to activate neurons to generate potential, and the cerebral cortex electrical signals are collected by the electrode points and transmitted to the interface end. The specific preparation process is as follows: step one, preparing the collection electrode and the optical stimulation electrode by MEMS process; step two, adjusting the initiator concentration, crosslinking agent concentration and type, and the proportion of doped silver nanowires to prepare the hydrogel substrate; step three, realizing the interface integration in sequence by transferring the optical stimulation electrode, adjusting the liquid hydrogel substrate and transferring the collection electrode. The device has the ability of multi-site optical stimulation and synchronous spatial multi-site neural signal monitoring of the brain cortex, and through the performance regulation of the hydrogel-polymer film optoelectronic neural electrode integrated interface, the device is endowed with super flexibility and adhesion, and can be more closely attached to the cerebral cortex.

[0011] The technical solution adopted by the application to solve the technical problems comprises the following steps:

[0012] A super flexible hydrogel-based optical brain-computer interface device comprises a flexible substrate, an electrode body, a micro LED chip array, a serpentine wire and an interface end; the electrode body comprises a collection electrode and an optical stimulation electrode; the serpentine wire comprises a recording serpentine wire and a power supply serpentine wire;

[0013] The collection electrode comprises a plurality of cortex recording electrode points, and the cortex recording electrode points are connected to the bonding pad of the interface end through the recording serpentine wire;

[0014] The cathode bonding pad and the anode bonding pad of the micro LED chip are connected to the bonding pad of the interface end by the power supply serpentine wire through different optical stimulation electrodes.

[0015] The micro-LED chip, the light stimulation electrode and the power supply serpentine wire are clamped in the middle of the two flexible substrates;

[0016] The cortex recording electrode point and the recording serpentine wire are attached to the outer surface of the flexible substrate, and are attached to the cerebral cortex area for work in use;

[0017] The micro-LED chip emits light in work, activates neurons to generate potential, and the cortex recording electrode point collects the cerebral cortex electrical signals induced by the micro-LED chip, and the multiple cerebral cortex electrical signals are transmitted simultaneously through the collection electrode.

[0018] Further, the flexible substrate is a super-flexible hydrogel substrate.

[0019] Further, the electrode body comprises an electrode substrate, a metal layer and an encapsulation layer.

[0020] Further, the cortex recording electrode point has a diameter of 50-200 microns and is attached to the surface of the cerebral cortex for collecting the cerebral cortex electrical signals.

[0021] Further, the micro-LED chip is encapsulated by transparent material polyisobutylene, and the length of the micro-LED chip is not greater than 270 microns and the width is not greater than 220 microns.

[0022] Further, the serpentine wires are all metal thin film materials, and the metal thin film material is gold or platinum or copper.

[0023] Further, the substrate layer and the encapsulation layer of the serpentine wire are both polyimide.

[0024] A preparation method of a super-flexible hydrogel-based optical computer interface device, comprising the following steps:

[0025] Step 1: evaporating or sputtering a layer of metal on a silicon wafer as a metal release layer;

[0026] Step 2: spin-coating a negative photosensitive polyimide on the surface of the silicon wafer, and preparing an electrode substrate by photolithography and development;

[0027] Step 3: sputtering a metal layer on the electrode substrate, then spin-coating a photoresist, patterning by photolithography, and then obtaining an electrode metal layer with a serpentine wire profile by ion beam etching or chemical wet etching;

[0028] Step 4: spin-coating a second layer of negative photosensitive polyimide on the electrode metal layer and performing photolithography and development to obtain an encapsulation layer;

[0029] Step 5: After the silicon wafer is soaked in the dilute hydrochloric acid solution, the silicon wafer is soaked, washed and dried with deionized water, and the release of the collection electrode and the light stimulation electrode is completed;

[0030] Step 6: 225-227 mg of recrystallized NIPAM monomer, 12.2-12.4 mg of MBA, 53-55 mg of KPS and 53-55 mg of SDS are weighed into four reagent bottles respectively, 1 mL of pure water is added to each, and the mixture is uniformly mixed;

[0031] Step 7: The NIPAM solution, the MBA solution and 95-105 microliters of the KPS solution are added to the flask respectively, 5 mL of pure water is further added to the flask, argon is bubbled for 30 minutes, and then the flask is sealed and placed in an environment of 60°C and 300 rpm for 30 minutes to obtain the PNG solution;

[0032] Step 8: The SDS solution is added, and after the bubbles above the liquid surface are eliminated, the flask is immediately sealed and placed in an environment of 60°C and 300 rpm for 30 minutes, and then the flask is taken out and cooled in an ice water bath to obtain the PNG solution;

[0033] Step 9: 335-340 mg of recrystallized NIPAM monomer and 53-55 mg of KPS are taken, 1 mL of pure water is added to the KPS, 0.9-1 mL of pure water, 1 mL of the PNG solution and an appropriate amount of the AgNWs solution are added to the NIPAM monomer, the mixture is ultrasonically shaken and uniformly mixed, finally 95-105 microliters of the KPS solution and 7-8 microliters of TEMED are added, argon is blown in, the flask is placed in an ice water bath for 2 hours and then taken out, and the hydrogel base in a gel state is obtained by standing;

[0034] Step 10: The micro-LED chip, the light stimulation electrode and the power supply serpentine wire are transferred to the surface of the hydrogel base by means of a water-soluble adhesive tape, and then the water-soluble adhesive tape is removed by using deionized water at room temperature, so that the micro-LED chip is ensured to be flatly bonded to the flexible base;

[0035] Step 11: The water on the surface of the hydrogel base is evaporated by standing at room temperature, a layer of liquid hydrogel precursor is spin-coated, the collection electrode and the recording serpentine wire are transferred to the surface of the top flexible base;

[0036] Step 12: The hydrogel is completely cured by standing, and the water-soluble adhesive tape is removed by using deionized water at room temperature, so that the device is prepared.

[0037] Preferably, the material of the metal release layer is chromium / gold or titanium / gold or tungsten / gold.

[0038] The beneficial effects of the present application are as follows:

[0039] 1、The application is endowed with super flexibility and adhesion by the use of super flexible material and the performance regulation of hydrogel-polymer film photoelectric neural electrode integrated interface, which significantly improves the mechanical matching of the device and brain soft tissue, effectively improves the long-term reliability of the system, and has important significance for reducing immune rejection reaction in long-term implantation.

[0040] 2、The device has the ability of brain cortex multi-site light stimulation and synchronous spatial multi-site neural signal monitoring by connecting the collection electrode points and light stimulation electrode points through independent interface ends and snake-shaped wires. BRIEF DESCRIPTION OF DRAWINGS

[0041] Figure 1 It is the overall structure schematic diagram of the super flexible hydrogel-based photo-computer interface device of the application.

[0042] Figure 2 It is the top view and local enlarged structure schematic diagram of the super flexible hydrogel-based photo-computer interface device of the application.

[0043] Figure 3 It is the planar processing structure schematic diagram of the super flexible hydrogel-based photo-computer interface device of the application.

[0044] Figure 4 It is the schematic diagram of the super flexible hydrogel-based photo-computer interface device of the application adhering to the mouse brain cortex for neural signal collection and the side structure schematic diagram thereof.

[0045] Figure 5 It is the in-situ collection schematic diagram of the super flexible hydrogel-based photo-computer interface device of the application after replacing the transparent conductive material in the second embodiment.

[0046] In the figure: 1-hydrogel base, 2-interface end, 3-electrode body, 4-collection electrode, 5-cortex recording electrode point, 6-micro LED chip, 7-light stimulation electrode, 8-recording snake-shaped wire, 9-power supply snake-shaped wire, 10-LED cathode pad, 11-LED anode pad, 12-super flexible hydrogel-based photo-computer interface device, 13-brain cortex region. DETAILED DESCRIPTION

[0047] The application will be further described below in combination with the drawings and embodiments.

[0048] The application provides a super-flexible hydrogel-based optical brain-computer interface device and a preparation method thereof. The application provides a super-flexible hydrogel-based optical brain-computer interface device and a preparation method thereof. The device has the abilities of multi-site optical stimulation of the cerebral cortex and synchronous spatial multi-site neural signal monitoring, and has super flexibility and adhesion through performance regulation of a hydrogel-polymer film photoelectric electrode integrated interface, can be more closely attached to the cerebral cortex, can be used as a new generation of implantable brain-computer interface tool with the functions of "optical stimulation-electric recording", and supports neural function circuit basic research based on optogenetics.

[0049] A super-flexible hydrogel-based optical brain-computer interface device, comprising a flexible substrate 1, an electrode body 3, a micro-LED chip 6 array, a serpentine wire and an interface end 2; the electrode body 3 comprises a collection electrode 4 and a light stimulation electrode 7; the serpentine wire comprises a recording serpentine wire 8 and a power supply serpentine wire 9;

[0050] The collection electrode 4 comprises a plurality of cortical recording electrode points 5, and the cortical recording electrode points 5 are connected to the pads of the interface end 2 through the recording serpentine wire 8;

[0051] The cathode pads 10 and the anode pads 11 of the micro-LED chip are connected to the pads of the interface end 2 by the power supply serpentine wire 9 through different light stimulation electrodes 7.

[0052] The micro-LED chip, the light stimulation electrode 7 and the power supply serpentine wire 9 are clamped between the two layers of flexible substrates 1;

[0053] The cortical recording electrode points 5 and the recording serpentine wire 8 are attached to the outer surface of the flexible substrate 1 and are attached to the cerebral cortex area 13 for work in use;

[0054] The micro-LED chip 6 emits light when working, activates neurons to generate potential emission, the cortical recording electrode points 5 collect the cerebral cortex electrical signals induced by the micro-LED chip 6, and a plurality of cerebral cortex electrical signals are simultaneously transmitted through the collection electrode 4.

[0055] Further, the flexible substrate 1 is a super-flexible hydrogel substrate.

[0056] Further, the electrode body 3 comprises an electrode substrate, a metal layer and an encapsulation layer.

[0057] Further, the skin recording electrode point 5 has a diameter of 50-200 microns and is attached to the cerebral cortex surface 13 for collecting the cerebral cortex electrical signal.

[0058] Further, the micro-LED chip 6 is encapsulated by transparent polyisobutylene, and the length of the micro-LED chip 6 is not greater than 270 microns and the width is not greater than 220 microns.

[0059] Further, the serpentine wires are all metal thin film materials, and the metal thin film material is gold or platinum or copper.

[0060] Further, the substrate layer and the encapsulation layer of the serpentine wire are both polyimide.

[0061] A preparation method of a super-flexible hydrogel-based optical computer interface device, comprising the following steps:

[0062] Step 1: evaporate or sputter a layer of metal on a silicon wafer as a metal release layer;

[0063] Step 2: spin-coat a negative photosensitive polyimide on the surface of the silicon wafer, and prepare an electrode substrate by photolithography and development;

[0064] Step 3: sputter a metal layer on the electrode substrate, then spin-coat a photoresist, patternize by photolithography, and then obtain an electrode metal layer with a serpentine wire profile by ion beam etching or chemical wet etching;

[0065] Step 4: spin-coat a second layer of negative photosensitive polyimide on the electrode metal layer and perform photolithography and development to obtain an encapsulation layer;

[0066] Step 5: after the silicon wafer is soaked in a dilute hydrochloric acid solution, it is then soaked in deionized water, rinsed and dried to complete the release of the recording electrode and the light stimulation electrode;

[0067] Step 6: weigh 225-227 mg of recrystallized NIPAM monomer, 12.2-12.4 mg of MBA, 53-55 mg of KPS and 53-55 mg of SDS into four reagent bottles respectively, and add 1 mL of pure water to each, and mix well;

[0068] Step 7: add the NIPAM solution, the MBA solution and 95-105 microliters of the KPS solution into the flask respectively, add 5 mL of pure water into the flask, and bubble with argon for 30 minutes;

[0069] Step 8: Add SDS solution, and blow gas above the liquid surface. After eliminating the bubbles above the liquid surface, seal immediately, and place in a 60℃, 300rpm environment for 30 minutes. Then, take out the flask and cool in an ice water bath to obtain the PNG solution;

[0070] Step 9: Take 335-340 mg of recrystallized NIPAM monomer and 53-55 mg of KPS, and add 1 mL of pure water to the KPS. Add 0.9-1 mL of pure water, 1 mL of PNG solution, and an appropriate amount of AgNWs solution to the NIPAM monomer, and ultrasonically shake to mix uniformly. Finally, add 95-105 microliters of KPS solution and 7-8 microliters of TEMED, blow in argon, and place in an ice water bath for 2 hours. Then, take out and stand to obtain the hydrogel base in a gel state;

[0071] Step 10: Transfer the micro-LED chip, light stimulation electrode 7, and power supply serpentine wire 9 to the surface of the hydrogel base by using a water-soluble adhesive tape. Then, wash with normal temperature deionized water to remove the water-soluble adhesive tape, and ensure flat bonding with the flexible base.

[0072] Step 11: Stand at room temperature to evaporate the water on the surface of the hydrogel base, and spin a layer of liquid hydrogel precursor. Then, transfer the collection electrode 4 and recording serpentine wire 8 to the surface of the top flexible base.

[0073] Step 12: Stand and wait for the hydrogel to completely solidify, and wash with normal temperature deionized water to remove the water-soluble adhesive tape, to complete the preparation of the device. Specific embodiments:

[0075] An ultra-flexible hydrogel-based optical computer interface device includes a flexible base 1, an electrode body 3, a micro-LED chip 6 array, and an interface end 2. The flexible base 1 is an ultra-flexible hydrogel base 1, the micro-LED chip array is located in the middle of the hydrogel base 1, the electrode body includes a collection electrode 4 and a light stimulation electrode 7, the collection electrode 4 is attached to the surface of the brain tissue 13 for work, and the interface end 2 is a unified interface end.

[0076] The collection electrode 4 includes a plurality of cortical recording electrode points 5, which are connected to the pads through recording serpentine wires 8.

[0077] The micro-LED chip array includes a plurality of micro-LED chips 6, which are connected to the pads through the light stimulation electrode 7 connected to the power supply serpentine wire 9.

[0078] The micro-LED chip 6 works by emitting light in the brain cortex tissue area 13, activating neurons to emit potential, and the cortical recording electrode points collect the brain cortex electrical signals induced by the micro-LED chip 6. A plurality of brain cortex electrical signals are simultaneously transmitted through the collection electrode 4.

[0079] The super-flexible hydrogel base 1 and the electrode body 3 are independently prepared by using a cross-linking process and MEMS micro-nano processing and transfer printing technology, respectively, and then are integrally processed and formed by using an interface integration process, so that the super-flexibility and adhesion of the device are ensured.

[0080] The electrode body includes the collection electrode 4 and the light stimulation electrode 7, and both of the electrodes are composed of an electrode substrate, a metal layer and an encapsulation layer.

[0081] The cortex recording electrode point 5 has a diameter of 50-200 microns and is attached to the cerebral cortex surface 13 to collect the cerebral cortex electrical signal.

[0082] The cathode pads 10 and the anode pads 11 of all the micro-LED chips are independently connected to the interface end by different power supply serpentine wires 9, so that the independent controllability of the light stimulation and the extensibility of the brain-computer interface device are ensured.

[0083] The micro-LED chip 6 is encapsulated by using transparent material polyisobutylene.

[0084] The micro-LED chip 6 has a length of not more than 270 microns and a width of not more than 220 microns, and is used to provide cerebral cortex light stimulation.

[0085] The serpentine wire includes the recording serpentine wire 8 and the power supply serpentine wire 9, and both of them are metal thin film materials.

[0086] The substrate layer and the encapsulation layer of the serpentine wire are both polyimide.

[0087] The metal thin film material encapsulated in the recording serpentine wire 8 and the power supply serpentine wire 9 is gold or platinum or copper. Embodiment:

[0089] Referring to Figure 1 As shown in the figure, the super-flexible hydrogel-based optical computer interface device of the application comprises a flexible base 1, a micro-LED chip 6, an electrode body 3 and an interface end 2. The flexible base 1 is a super-flexible hydrogel base, the micro-LED chip 6 is located in the middle of the hydrogel base, the electrode body includes a collection electrode 4 and a light stimulation electrode 7, and the collection electrode is attached to the surface of the brain tissue to work. The number and size of all the cortex recording electrode points 5 and the micro-LED chips 6 can be designed according to actual needs, and this embodiment mainly faces rodents such as mice.

[0090] Referring to Figure 2 As shown in the figure, the cortex recording electrode point 5 is connected to the interface end through the recording serpentine wire 8, and the micro-LED chip 6 is connected to the interface end through the power supply serpentine wire 9. All the LED cathode pads 10 and the anode pads 11 are independently powered, so that the independent controllability of the light stimulation and the extensibility of the whole device are effectively ensured.

[0091] Referring to Figure 3As shown, a preparation method of a super-flexible hydrogel-based optical computer interface device, comprising the following steps:

[0092] Step 1: using a clean silicon wafer, evaporating or sputtering a layer of metal on the silicon wafer as a metal release layer;

[0093] Step 2: spin coating a negative photosensitive type polyimide on the surface of the silicon wafer, preparing an electrode substrate by photolithography and development method;

[0094] Step 3: sputtering a chromium / gold or titanium / gold or tungsten / gold metal layer on the electrode substrate, then spin coating a photoresist, patterning by photolithography, and then obtaining an electrode metal layer with a serpentine line profile by ion beam etching or chemical wet etching;

[0095] Step 4: spin coating a second layer of negative photosensitive type polyimide on the electrode metal layer and photolithography and development to obtain an encapsulation layer;

[0096] Step 5: immerse the whole silicon wafer in a 5% dilute hydrochloric acid solution for 24 hours, and finally immerse, rinse and dry with deionized water to complete the release of the collection electrode and the light stimulation electrode;

[0097] Step 6: respectively weigh 225-227 mg of recrystallized NIPAM monomer, 12.2-12.4 mg of MBA, 53-55 mg of KPS and 53-55 mg of SDS into four reagent bottles, and add 1 mL of pure water to each, and mix well;

[0098] Step 7: respectively add NIPAM solution, MBA solution and 95-105 microliters of KPS solution into the flask, add 5 mL of pure water to the flask, and bubble with argon for 30 minutes;

[0099] Step 8: add SDS solution and blow gas above the liquid surface, after eliminating the bubbles above the liquid surface, immediately seal, place in a 60℃, 300rpm environment for 30 minutes, then take out the flask and place in an ice water bath to cool to obtain a PNG solution;

[0100] Step 9: take 335-340 mg of recrystallized NIPAM monomer and 53-55 mg of KPS, add 1 mL of pure water to the KPS, add 0.9-1 mL of pure water, 1 mL of PNG solution and an appropriate amount of AgNWs solution to the NIPAM monomer, ultrasonic oscillation and mix well, finally add 95-105 microliters of KPS solution and 7-8 microliters of TEMED, blow in a certain amount of argon, place in an ice water bath for 2 hours, then take out and stand to obtain a hydrogel in a gel state.

[0101] Step 10: The LED light stimulation electrode is transferred to the surface of the hydrogel substrate with high curing degree and thickness not exceeding 200 microns by a water-soluble adhesive tape, and then the water-soluble adhesive tape is removed by flushing with deionized water at room temperature, to ensure that the serpentine line structure LED light stimulation electrode and the underlying hydrogel substrate are flatly bonded;

[0102] Step 11: Evaporate the water on the surface of the underlying hydrogel substrate at room temperature, spin-coat a layer of liquid hydrogel precursor, and transfer the serpentine line structure collection electrode to the surface of the top hydrogel substrate which has integrated the LED light stimulation electrode;

[0103] Step 12: Wait for the hydrogel to fully cure, and then remove the water-soluble adhesive tape by flushing with deionized water at room temperature, to complete the final interface integration.

[0104] Reference Figure 4 As shown in the figure, the super-flexible hydrogel-based optical computer interface device 12 is attached to the mouse cerebral cortex region 13, and has a very high degree of fit. Even at the junction of the two sides of the brain region with a large slope, a good fit can still be formed by using the high compliance and deformation ability of the super-flexible hydrogel substrate. The super-flexible hydrogel-based optical computer interface device can have an electrode extensibility of more than 30%, and can achieve a very high signal acquisition quality. The micro-LED chip 6 emits light in different regions of the cerebral cortex brain tissue, activates neurons to emit potential, and the cortical recording electrode point collects the ECoG signal induced by the micro-LED chip. Multiple cerebral cortex electrical signals are transmitted to the interface end at the same time. Thus, the brain cortex multi-site light stimulation and synchronous spatial multi-site neural signal monitoring are realized. The correlation analysis of the synchronous recorded neural signals can not only be used to answer the complex action potential transmission process between neurons, but also can more comprehensively and effectively support the research on neural circuit function and the pathogenesis of brain diseases, and provide a high-precision, high-reliability, and high-durability implantable cortical "electric collection-light stimulation" brain-computer interface front-end tool for basic brain science and clinical brain disease research, and lay a technical foundation for neural decoding and neural system disease diagnosis and treatment in the back end.

[0105] In a specific embodiment two, the conductive material of the recording serpentine wire 8 and the power supply serpentine wire 9 is replaced. The most commonly used conductive material for encapsulating the recording serpentine wire and the power supply serpentine wire is a metal film material, such as gold, platinum, or copper, etc. However, when the micro-LED chip is turned on and off, it will bring significant electromagnetic interference, and the noise component in the recording signal is further aggravated due to the existence of photoelectric effect, which may even drown out the amplitude of the neural signal induced by light activation. In addition, the metal film material is not transparent, and may block the light generated by the micro-LED chip to some extent. When collecting neural signals, only ectopic collection can be performed to obtain the signals in the vicinity of the micro-LED chip. Therefore, as shown in the figure, the recording serpentine wire 8 and the power supply serpentine wire 9 are replaced by a transparent conductive material, such as ITO, graphene, etc. Figure 5As shown, the replaceable conductive material is graphene, silver nanowire, indium tin oxide, etc. with high transparency, and light is transmitted vertically through the electrode site to the brain area to realize in-situ working ability of light stimulation induction and neural signal acquisition. At the same time, the noise interference resistance of the recording electrode site under the light emitting working condition of the micro-LED chip is effectively improved to obtain the neural signal without light-induced artifacts.

[0106] In a specific embodiment three, the performance of the super-flexible hydrogel base is improved by changing the material of the super-flexible hydrogel base. The super-flexible hydrogel base is in direct contact with the cerebral cortex and needs to have good biocompatibility and antibacterial property to reduce the damage to the brain tissue and increase the service life. The performance can be improved by using hydrogel materials with high antibacterial property and biocompatibility, such as natural antibacterial hydrogels, TiO2 / poly composite hydrogel inorganic antibacterial hydrogel or organic antibacterial hydrogel, etc.; since the hydrogel base needs to be adhered to the cerebral cortex and the neural electrode, and at the same time protect the internal structure, it needs to have excellent adhesion and sealing property, which can be improved by using heat-sensitive modified chitin hydrogel with excellent adhesion property; since the micro-LED generates heat when working, the heat will greatly affect the acquisition effect of the neural signal and the service life of the device, so the base material should have good thermal conductivity. A thin film with high transparency and strong thermal conductivity, such as diamond thin film, can be deposited on the back of the hydrogel base 1 to enhance the heat dissipation capacity of the device.

Claims

1. A super flexible hydrogel-based optical computer interface device, characterized in that, The flexible substrate, the electrode body, the micro-LED chip array, the serpentine wire and the interface end; the electrode body includes a collection electrode and a light stimulation electrode; the serpentine wire includes a recording serpentine wire and a power supply serpentine wire; The flexible substrate is a super-flexible hydrogel substrate; The collection electrode includes a plurality of skin recording electrode points, and the skin recording electrode points are connected to the pads of the interface end through the recording serpentine wire; the collection electrode and the light stimulation electrode each include an electrode substrate, a metal layer and an encapsulation layer; wherein the skin recording electrode points have a diameter of 50-200 microns and are attached to the surface of the cerebral cortex for collecting the cerebral cortex electrical signals; The cathode pads and the anode pads of the micro-LED chip are connected to the pads of the interface end by the power supply serpentine wire through different light stimulation electrodes; wherein the micro-LED chip is encapsulated by a transparent material polyisobutylene, and the length of the micro-LED chip is not greater than 270 microns and the width is not greater than 220 microns; The micro-LED chip, the light stimulation electrode and the power supply serpentine wire are clamped between the two layers of flexible substrates; The skin recording electrode points and the recording serpentine wire are attached to the outer surface of the flexible substrate and work in the cerebral cortex region during use; The micro-LED chip emits light during work, activates neurons to emit potential, the skin recording electrode points collect the cerebral cortex electrical signals induced by the micro-LED chip, and a plurality of cerebral cortex electrical signals are transmitted simultaneously through the collection electrode.

2. The super flexible hydrogel-based optical computer interface device of claim 1, wherein, The serpentine wire is a metal thin film material, and the metal thin film material is gold, platinum or copper.

3. The super flexible hydrogel-based optical computer interface device of claim 1, wherein, The substrate layer and the encapsulation layer of the serpentine wire are both made of polyimide.

4. A method of manufacturing an interface device as claimed in claim 1, characterized in that, The method comprises the following steps: Step 1: evaporate or sputter a layer of metal on a silicon wafer as a metal release layer; Step 2: spin-coat a negative photosensitive polyimide on the surface of the silicon wafer, and prepare an electrode substrate by photolithography and development; Step 3: sputter a metal layer on the electrode substrate, then spin-coat a photoresist, patternize by photolithography, and then obtain an electrode metal layer with a serpentine wire profile by ion beam etching or chemical wet etching; Step 4: spin-coat a second layer of negative photosensitive polyimide on the electrode metal layer and perform photolithography and development to obtain an encapsulation layer; Step 5: after the silicon wafer is soaked in a dilute hydrochloric acid solution, it is then soaked, rinsed and dried with deionized water to complete the release of the collection electrode and the light stimulation electrode; Step 6: weigh 225-227 mg of recrystallized NIPAM monomer, 12.2-12.4 mg of MBA, 53-55 mg of KPS and 53-55 mg of SDS into four reagent bottles respectively, add 1 mL of pure water to each, and mix well; Step 7: add the NIPAM solution, the MBA solution and 95-105 microliters of the KPS solution into a flask respectively, add 5 mL of pure water to the flask, and bubble with argon for 30 minutes; Step 8: add the SDS solution and blow gas above the liquid surface, after the bubbles above the liquid surface are eliminated, immediately seal, and place in an environment of 60 ℃ and 300 rpm for 30 minutes, then take out the flask and cool it in an ice water bath to obtain a PNG solution; Step 9: Take 335-340 mg of recrystallized NIPAM monomer and 53-55 mg of KPS, add 1 mL of pure water to the KPS, add 0.9-1 mL of pure water, 1 mL of PNG solution and an appropriate amount of AgNWs solution to the NIPAM monomer, ultrasonic oscillation to mix uniformly, finally add 95-105 microliters of KPS solution and 7-8 microliters of TEMED, blow argon, put into ice water bath for 2 hours, take out, and get the gel state hydrogel substrate; Step 10: Transfer the micro-LED chip, light stimulation electrode and power supply serpentine wire to the surface of the hydrogel substrate by water-soluble adhesive tape, then wash with normal temperature deionized water to remove the water-soluble adhesive tape, and ensure flat bonding with the flexible substrate; Step 11: Evaporate the water on the surface of the hydrogel substrate at room temperature, spin a layer of liquid hydrogel precursor, transfer the collection electrode and recording serpentine wire to the surface of the top flexible substrate; Step 12: Wait for the hydrogel to completely solidify, wash with normal temperature deionized water to remove the water-soluble adhesive tape, and complete the preparation of the device.

5. The preparation method according to claim 4, characterized in that, The material of the metal release layer is chromium / gold or titanium / gold or tungsten / gold.

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