Instrument capable of being separated through light control as well as preparation method and application of instrument

Abstract

The invention discloses an instrument capable of being separated through light control and a preparation method and application of the instrument, and belongs to the technical field of biomedical engineering and flexible electronics. The instrument capable of being separated through light control comprises a flexible substrate layer, an electrode layer and a gel integration layer, the preparation method comprises the following steps: (1) forming an electrode pattern on a silicon wafer through photoetching, and carrying out oxygen plasma treatment to prepare a hydrophilic surface; (2) spin-coating a water-soluble polymer solution to form a sacrificial layer; (3) spin-coating silicone rubber pre-polymerized liquid and curing to form a flexible substrate layer; (4) dissolving the sacrificial layer with water to realize demolding, and embedding a patterned conductive material into the surface to form an electrode layer; and (5) coating the photo-responsive adhesive hydrogel pre-polymerization liquid, and performing cross-linking curing to form a gel integration layer, thereby obtaining the photo-responsive adhesive hydrogel. Through integrated structural design and functional material integration, the brain-computer interface ECoG electrode with high flexibility, high adhesion, high conductivity and controllable debonding capacity and the like is provided, and a technical basis and an application platform are provided for a next-generation intelligent implantable brain-computer system.

Description

Technical Field

[0001] The present invention relates to the fields of biomedical engineering and flexible electronic technology, and more particularly to a light-controlled detachable device and a preparation method and application thereof. Background Art

[0002] In recent years, with the rapid development of brain science research and brain-computer interface technology, the design of flexible bioelectrodes and implantable devices faces two core challenges: mechanical property adaptability and biocompatibility. Traditional rigid electrodes (such as metal or silicon-based electrodes) have significant differences in modulus (1-10kPa) from brain tissue, which can easily induce inflammatory reactions and signal attenuation. For example, although the Utah electrode is approved by the FDA, its rigid structure causes the signal quality to drop by 40%-60% within 6 months after implantation. Although flexible substrates such as polyimide (modulus 1-3GPa) are improved compared to metals, they are still 3-5 orders of magnitude higher than brain tissue.

[0003] In terms of signal acquisition capability, scalp electroencephalogram (EEG) has a signal-to-noise ratio of less than 0.1 due to skull attenuation, while electrocorticogram (ECoG) has become an important tool for clinical research because of its high spatiotemporal resolution and minimal invasiveness. For example, patent CN118592963 A discloses an ECoG electrode and a preparation method thereof. The implantable electrode of the invention includes a flexible support layer, an electrode metal layer, and a packaging layer. By setting different materials on the exposed surfaces of the electrode contacts and solder joints, different materials can give full play to their respective advantages. However, the base material used in the invention is polyimide, which has a Young's modulus (GPa level) much higher than that of brain tissue (kPa level), and is prone to interface micro-motion damage or signal drift due to mechanical mismatch.

[0004] Patent CN 111938632 A discloses a brain signal acquisition device and its preparation method. The device comprises a biological silk protein substrate and brain electrodes positioned on the silk protein substrate. This device offers advantages such as multifunctionality, implantability, biodegradability, long-term in vivo stable recording, and high spatiotemporal resolution. However, the silk protein adhesive used lacks the ability to dynamically adapt to brain tissue deformation. Furthermore, long-term implantation can lead to interfacial debonding due to inflammatory reactions or fluid infiltration, compromising signal quality.

[0005] In recent years, the development of flexible electronics has promoted the application of soft materials such as PDMS (polydimethylsiloxane) and hydrogels, but limitations still exist. For example, patent CN 114271828 A discloses a degradable high-array flexible device for brain-computer interface, including a flexible substrate, flexible conductive electrodes, a support layer, an electrical insulation layer, and a semiconductor layer stacked in sequence. The flexible sensor device is made of materials with good biocompatibility and biodegradability, which enables the acquisition of signals with a high level of temporal and spatial resolution, and can achieve breakthrough monitoring and recording of physiological electrical signals at the cellular level. However, this patent suffers from interface packaging defects: the interface between the flexible substrate and the metal electrode is prone to cracking due to mechanical deformation, leading to electrode failure.

[0006] Patents CN 113057637 A and CN 117736467 A disclose two flexible bioelectrodes based on conductive bioadhesive hydrogels and their preparation methods. These electrodes possess mechanical properties that enhance their compatibility with brain tissue and enable the acquisition of higher-quality signals. However, these electrodes currently lack the ability to be non-invasively removed on demand after signal acquisition, limiting their clinical safety.

[0007] Therefore, how to improve the electrode's adaptability to brain tissue, signal acquisition stability, and controllable removal capability after surgery is an urgent problem that needs to be solved by those skilled in the art. Summary of the Invention

[0008] In view of this, the purpose of the present invention is to provide a light-controlled detachable device and its preparation method and application, so as to solve the technical bottlenecks of existing ECoG electrodes in tissue flexibility, fitting stability, reliability of biological signal collection and non-invasive detachment after surgery.

[0009] In order to achieve the above object, the present invention adopts the following technical solutions:

[0010] A light-controlled detachable device comprises a flexible base layer, an electrode layer and a gel integration layer;

[0011] Wherein, the flexible base layer is composed of a silicon-based elastic polymer material;

[0012] The electrode layer is composed of a patterned conductive material and is embedded in the flexible base layer;

[0013] The gel integration layer is composed of a conductive photoresponsive adhesive hydrogel and covers the surface of the electrode layer and the flexible substrate layer.

[0014] In the present invention, the gel integration layer forms an integrated bonding structure with the flexible base layer and the patterned conductive material. In addition, the electrode layer can directly serve as the base layer if it is self-supporting, without the need for an additional flexible base layer.

[0015] The novelty and applicability of the light-controlled detachable device of the present invention are as follows:

[0016] Through integrated structural design and functional material integration, the present invention provides a brain-computer interface ECoG electrode with high flexibility, high adhesion, high conductivity and controllable debonding ability, providing a technical foundation and application platform for the next generation of intelligent implantable brain-computer systems.

[0017] The present invention prepares an electrocortical (ECoG) electrode for an implantable brain-computer interface (BCI) through the collaborative design of a photoresponsive adhesive gel integration layer and a flexible substrate-electrode. This electrode overcomes the technical bottlenecks of traditional ECoG electrodes in terms of brain tissue adhesion stability, long-term signal acquisition reliability, and controllable on-demand removal after surgery. It is suitable for neural signal acquisition, brain disease diagnosis and treatment, and the construction of brain-computer interaction systems.

[0018] The present invention prepares an ECoG electrode based on photoresponsive adhesive gel integration. Through the integrated design of flexible substrate-electrode layer-gel integration layer, combined with light-controlled debonding function and conductivity optimization, the electrode's brain tissue adaptability, signal acquisition stability and controllable removal capability after surgery are significantly improved, providing an innovative solution for the next generation of implantable brain-computer interface systems.

[0019] The present invention prepares the flexible substrate part by photolithographic pattern transfer, so that the patterned electrode can be better embedded with the flexible substrate. At the same time, the selected bioadhesive hydrogel can simultaneously realize the integrated packaging of the flexible substrate layer and the metal electrode layer and form a stable fit with the soft brain tissue. The cortical brain electrode thus prepared has good flexibility, stable tissue adhesion and expandable light-controlled debonding function, and is suitable for the construction of implantable brain-computer interface systems, biological signal collection and on-demand removal.

[0020] The preparation method of the present invention combines standardized micro-nano processing with soft material technology to ensure the structural integrity, adhesion stability and functional controllability of the device.

[0021] Furthermore, the above-mentioned silicon-based elastic polymer material is a two-component room temperature curing silicone rubber (such as series), medical silicone (PDMS, such as ), medical polyurethane (PU), polylactic acid-glycolic acid copolymer (PLGA), polycaprolactone (PCL), polyvinylidene fluoride (PVDF) and its copolymers and polyvinyl alcohol-polyacrylic acid (PVA-PAA) interpenetrating network materials.

[0022] A further beneficial effect of the above is that the silicon-based elastic polymer material selected in the present invention can give the electrode good tissue mechanical matching and flexible adhesion. It is a type of two-component room temperature curing silicone rubber (RTV Silicone Rubber) produced by Smooth-On. Its characteristics are: soft, highly elastic, and the medical / food grade version is biocompatible. It is commonly used in flexible electronics, bionic robots, soft devices, skin models, etc. Different from traditional condensation silicone rubber, It is an addition-type silicone rubber that does not release low molecular weight substances during the cross-linking process, and the curing process is more stable and more environmentally friendly.

[0023] Furthermore, the above-mentioned patterned conductive material is at least one of gold (Au), platinum (Pt), platinum-iridium alloy, magnesium (Mg), zinc (Zn), poly(3,4-ethylenedioxythiophene)-polystyrene sulfonic acid (PEDOT:PSS), graphene, carbon nanotube film, laser-induced graphene (LIG) and gallium-indium-tin alloy (Galinstan).

[0024] A further beneficial effect of the above is that the patterned conductive material selected by the present invention can be embedded in a flexible substrate to form a precise electrode pattern, and also supports liquid metal or degradable metal (Mg, Zn) materials to meet the application needs of multiple scenarios.

[0025] Furthermore, the above-mentioned photoresponsive adhesive hydrogel includes a macromonomer containing a photo-controlled cleavage unit and an oxidant; wherein the macromonomer containing a photo-controlled cleavage unit is composed of a polymer chain, a photoresponsive cleavage functional group and a molecular fragment containing a catechol structure covalently connected by chemical bonds.

[0026] A further beneficial effect of the above-mentioned method is that the photoresponsive adhesive hydrogel of the present invention is a photoresponsive hydrogel composed of a hydrophilic or amphiphilic polymer main chain as a skeleton, and photoresponsive cleavage functional groups bonded to adhesion groups containing catechol structures through oxidative cross-linking. Under irradiation with ultraviolet light of a wavelength of 300-405 nm, end group decomposition occurs, resulting in a gel-sol transition, thereby allowing the ECoG electrode to be detached from the surface of the brain tissue without the need for large traction force.

[0027] Furthermore, the above-mentioned polymer chain is a hydrophilic polymer main chain or an amphiphilic polymer main chain containing a flexible chain segment, preferably at least one of polyethylene glycol (PEG), polyoxyethylene-polyoxypropylene-polyoxyethylene (PEO-PPO-PEO) block copolymer (Pluronic), poly(polyethylene glycol methacrylate) (POEGMA), polycaprolactone-polyethylene glycol (PCL-PEG) block copolymer, poly(lactic acid-glycolic acid)-polyethylene glycol (PLGA-PEG) block copolymer and poly(lactic acid-glycolic acid)-polyethylene glycol-poly(lactic acid-glycolic acid) (PLGA-PEG-PLGA) triblock copolymer, preferably at least one of linear polyethylene glycol, three-arm polyethylene glycol, four-arm polyethylene glycol and eight-arm polyethylene glycol, with a number average molecular weight of 1000-50000 Daltons.

[0028] A further beneficial effect of the above is that the polymer chains selected in the present invention are used to provide controllable mechanical properties and network flexibility.

[0029] Furthermore, the photoresponsive cleavage functional group is connected to the end or side group of the polymer chain and is at least one of o-nitrobenzyl ester, coumarin, anthracene, thymine and O-acyl oxime.

[0030] A further beneficial effect of the above is that the photoresponsive cleavage functional group selected in the present invention can undergo a cleavage reaction under irradiation with ultraviolet light of a specific wavelength (300-405 nm), thereby achieving structural disintegration or degradation of the hydrogel.

[0031] Furthermore, the molecular fragment containing catechol structure is at least one of dopamine, catechin, epicatechin, protocatechuic acid, catecholamine and tannic acid.

[0032] A further beneficial effect of the above method is that the molecular fragments containing catechol structures selected by the present invention can form strong adhesion to the surfaces of various materials and have antioxidant and tissue-friendly properties.

[0033] Furthermore, the above-mentioned photoresponsive adhesive hydrogel further includes a conductive material, which is at least one of a conductive polymer, a carbon-based filler, a metal nanoparticle, an ion conductive medium and a composite conductive network; wherein,

[0034] 1) Conductive polymer: poly(3,4-ethylenedioxythiophene)-polystyrene sulfonic acid (PEDOT:PSS) nanofibers, with a mass fraction of 5%-15%;

[0035] 2) Carbon-based filler: graphene oxide (GO) or carboxylated carbon nanotubes (CNT-COOH), with a mass fraction of 0.1%-3%;

[0036] 3) Metal nanoparticles: gold nanoparticles (AuNPs, particle size 10-50 nm) or silver nanowires (AgNWs, diameter ≤100 nm), with a mass fraction of 0.5%-5%;

[0037] 4) Ionic conductive medium: lithium chloride (LiCl) or choline-acrylic acid ionic liquid, with a molar concentration of 0.1-1M;

[0038] 5) Composite conductive network: PEDOT:PSS is blended with liquid metal droplets (Galinstan, particle size 1-5 μm), with the liquid metal accounting for 10%-30% by mass.

[0039] A further beneficial effect of the above is that the present invention preferably uses a photoresponsive biohydrogel composed of o-nitrobenzyl ester-dopamine modified polyethylene glycol (PEG-o-NB-DA) as the surface encapsulation layer. The gel has excellent tissue adhesion, biocompatibility and light-triggered debonding ability, and can also be incorporated with conductive components such as PEDOT:PSS nanofibers, GO, AuNPs, AgNWs, etc. to improve its interfacial conductivity and signal stability.

[0040] A method for preparing the above-mentioned light-controllable detachable device specifically comprises the following steps:

[0041] (1) Electrode patterns were formed on a silicon wafer by photolithography, and then oxygen plasma treatment was performed to prepare a hydrophilic surface;

[0042] (2) spin coating a water-soluble polymer solution on the surface of the electrode pattern to form a sacrificial layer;

[0043] (3) spin coating the silicone rubber prepolymer on the sacrificial layer and curing it to form a flexible base layer;

[0044] (4) dissolving the sacrificial layer with water to achieve demolding, and embedding a patterned conductive material on the surface to form an electrode layer;

[0045] (5) The photoresponsive adhesive hydrogel prepolymer is coated on the surface of the electrode layer and the flexible substrate layer, and cross-linked and cured to form a gel integration layer, thereby obtaining a device that can be light-controlled and detached.

[0046] Furthermore, in the above step (5), the preparation method of the photoresponsive adhesive hydrogel prepolymer solution is:

[0047] 1) Synthesizing intermediate A containing a photoresponsive cleavage functional group;

[0048] 2) coupling the intermediate A with a molecular fragment containing a catechol structure to obtain a photosensitive adhesion small molecule structural unit B;

[0049] 3) coupling the photosensitive adhesive small molecule structural unit B with a polymer chain containing an active functional group in a solvent under the catalytic action of a condensing agent to obtain a macromonomer containing a photo-controlled bond-breaking unit; wherein the condensing agent is at least one of 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate / N,N-diisopropylethylamine, 1-ethyl-(3-dimethylaminopropyl)carbodiimide / N-hydroxysuccinimide, N,N'-dicyclohexylcarbodiimide / 1-hydroxybenzotriazole, 1,1'-carbonyldiimidazole, and triphosgene; and the solvent is at least one of N,N-dimethylformamide, dimethyl sulfoxide, and N-methylpyrrolidone;

[0050] 4) dissolving the macromonomer containing the photo-scissile bond in a dispersion medium to obtain a photoresponsive adhesive hydrogel prepolymer solution; wherein the dispersion medium is a 10 mM PBS buffer solution containing 0.15 M NaCl and a pH of 7.4, physiological saline, or simulated cerebrospinal fluid.

[0051] Furthermore, in the above step (5), the coating is performed by spin coating or spray coating; wherein, the rotation speed of the spin coating method is 1000-2000 rpm, and the gel thickness is controlled at 20-100 μm; the air pressure of the spray gun of the spray coating method is 0.1-0.3 MPa, and the spraying distance is 10-20 cm, forming a gradient pore structure with a pore size of 5-50 μm.

[0052] Furthermore, in the above step (5), the oxidant selected for cross-linking and curing is sodium periodate, ferric chloride or H2O2 / HRP.

[0053] Preferably, the method for preparing the above-mentioned light-controllable detachable device specifically comprises the following steps:

[0054] (1) Electrode pattern construction

[0055] A 4-inch single-polish silicon wafer was used as the substrate. After cleaning the surface, SU-82075 negative photoresist was spin-coated at 1000 rpm for 60 seconds to form a pattern layer with a thickness of 70-100 μm. A soft bake was then performed, with the recommended temperature increasing from 65°C (5 minutes) to 95°C (30 minutes) to remove the solvent.

[0056] The electrode pattern is drawn using computer-aided design (CAD) software and input into a laser direct write lithography system (such as the Heidelberg DWL series) via CleWin 5 for exposure. After exposure, a post-exposure bake is performed at 65°C (1 minute) → 95°C (10 minutes). Finally, the pattern is developed with a SU-8 developer for 10-15 minutes to remove the unexposed areas, resulting in an electrode pattern with micron-level precision.

[0057] (2) Hydrophilic treatment of substrate surface

[0058] The patterned silicon wafer was placed in an oxygen plasma treatment instrument with an oxygen flow rate of 50 sccm, a treatment power of 100 W, and a treatment time of 120 s. After treatment, the surface contact angle dropped to ≤10°, significantly improving the subsequent interfacial bonding ability between the PVA film and PDMS.

[0059] (3) Construction of PVA sacrificial layer and PDMS flexible substrate

[0060] A polyvinyl alcohol (PVA) aqueous solution (degree of polymerization 2400, degree of alcoholysis 88%) with a concentration of 500 mg / mL was evenly spin-coated on the patterned area at a spin-coating speed of 4000 rpm, a drying temperature of 60° C., and a drying time of 30 min to form a uniform and soluble sacrificial layer.

[0061] PDMS (Sylgard 184) prepolymer components A and B were then mixed in a 10:1 mass ratio. After thorough degassing (vacuuming for 30 minutes), they were spin-coated at 500 rpm onto the PVA layer to form a flexible substrate layer approximately 150 μm thick. The curing temperature was 80°C for 2 hours.

[0062] (4) Demolding and electrode fitting

[0063] After the PDMS is fully cured, the entire silicon wafer is immersed in room temperature deionized water for 1 hour to allow the PVA sacrificial layer to fully dissolve and the PDMS structure to automatically release from the silicon wafer surface. At this point, the electrode pattern has been completely transferred to the flexible PDMS substrate, maintaining pattern consistency.

[0064] Silver wires (≈100 μm in diameter) are then embedded in pre-defined grooves in the PDMS surface, corresponding to the photolithographic electrode channels. A small amount of uncured PDMS is then used to encapsulate the pin connection area and heat-cured again to secure the wire position.

[0065] (5) Preparation of photoresponsive hydrogel integration layer

[0066] o-Nitrobenzyl ester-dopamine-modified polyethylene glycol (PEG-o-NB-DA) was prepared into a 22 wt% prepolymer solution in PBS buffer. Conductive enhancement components (such as PEDOT:PSS, GO, and AuNPs) can be optionally doped to enhance signal conduction.

[0067] The prepolymer liquid was evenly covered on the surface of the electrode and substrate by spin coating (1000-2000 rpm, 60 s) or spraying (air pressure 0.2 MPa, spray distance 15 cm). After being treated with an oxidative cross-linking agent such as sodium periodate or FeCl3 (volume ratio 1:5, 5 wt%), it was allowed to stand for 3 minutes to complete the gel cross-linking and form a dense photoresponsive adhesion layer.

[0068] The present invention also seeks to protect the use of the above-mentioned light-controllable detachable device or the light-controllable detachable device obtained by the above-mentioned preparation method in constructing an implantable brain-computer interface system for EEG signal acquisition, biological tissue bonding and postoperative on-demand debonding and removal.

[0069] It can be seen from the above technical solution that compared with the prior art, the beneficial effects of the present invention are as follows:

[0070] 1. Better flexibility: The base modulus matches that of brain tissue, significantly reducing mechanical stress and inflammation risks;

[0071] 2. More stable adhesion: Photoresponsive hydrogels provide stable adhesion to biological tissues and controllable debonding;

[0072] 3. More reliable interface: Conductive gel simultaneously realizes the triple functions of encapsulation, conduction and adhesion;

[0073] 4. More compatible processes: adaptable to a variety of conductive materials, multiple processing platforms and various brain region morphologies;

[0074] 5. Wider application: Suitable for scenarios such as implantable neural signal acquisition systems, brain disease intervention platforms and flexible neural interface devices. BRIEF DESCRIPTION OF THE DRAWINGS

[0075] Figure 1 Schematic diagram of the overall structure of the ECoG electrode in Example 1;

[0076] Figure 2 Schematic diagram of the layered structure of the ECoG electrode in Example 1,

[0077] Figure 3 Flow chart of the preparation process of the ECoG electrode in Example 1;

[0078] Figure 4 This is the electrical impedance spectroscopy (EIS) test diagram of the ECoG electrode in Example 1;

[0079] Figure 5 The linear voltammetry (LSV) test curve and the calculated resistivity result of the ECoG electrode in Example 1 are shown;

[0080] Figure 6 1 is a cyclic voltammetry (CV) test curve of the ECoG electrode in Example 1 and a graph showing the charge storage capacity calculated;

[0081] Figure 7 The constant current charge and discharge (GCD) test curve of the ECoG electrode in Example 1 and the calculated charge storage capacity change results with the number of charge and discharge times;

[0082] Figure 8 The electrophysiological signal acquisition results and channel correlation coefficients of the cerebral cortex of SD rats using the ECoG electrodes in Example 1 are as follows;

[0083] Figure 9 The results of collecting electrophysiological signals from the cerebral cortex of SD rats using the steady-state induced visual potential method using the ECoG electrodes in Example 1 and performing Fourier transform and signal-to-noise ratio analysis on the signals;

[0084] Figure 10 This is the experimental process of removing the ECoG electrode by light-triggered debonding 10 days after implantation in the brain of SD rats in Example 1, as well as the results of immunofluorescence staining of brain injury sections. DETAILED DESCRIPTION

[0085] The following is a clear and complete description of the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making any creative efforts are within the scope of protection of the present invention.

[0086] Example 1

[0087] The invention relates to a method for preparing a device capable of light-controlled detachment, specifically an electrocortico-gyroscope (ECoG) electrode containing gel, using PDMS as a flexible substrate material, such as Figure 1-3 As shown, Figure 2 The three-layer structure of the flexible base layer, electrode layer and gel integration layer and the schematic diagram of the complete brain-computer interface that closely fits the surface of brain tissue are shown. Figure 3 The schematic diagram shows the process of flexible substrate patterning, PVA sacrificial layer and PDMS molding, silver wire embedding and PDMS encapsulation, and PEG-o-NB-DA gel integration, which includes the following steps:

[0088] (1) SU-82075 photoresist was spin-coated on a 4-inch single-polished silicon wafer (1000 rpm, 80 μm thickness). After soft baking, the electrode pattern was formed using laser direct writing technology.

[0089] (2) After development, oxygen plasma treatment (50 sccm, 100 W, 120 s) was performed to enhance surface hydrophilicity;

[0090] (3) Spin coating of 500 mg / mL PVA aqueous solution (4000 rpm) and drying at 60 °C for 30 min to form a sacrificial layer;

[0091] (4) Prepare PDMS (Sylgard 184, 10:1), degas, and spin-coat (500 rpm) to a thickness of 150 μm, then cure at 80°C for 2 h;

[0092] (5) Demolding the PDMS membrane and embedding a 0.1 mm diameter silver wire;

[0093] (6) 0.9 mL of PEG-o-NB-DA hydrogel prepolymer solution was added with 0.1 mL of 5.4 wt% sodium periodate solution and spin-coated on the PDMS-silver surface (1500 rpm) before complete cross-linking. The gel integration was completed after 3 min.

[0094] The obtained electrode has good flexibility, can adhere to the surface of the cerebral cortex, and has light-responsive debonding properties.

[0095] The preparation method of PEG-o-NB-DA hydrogel prepolymer solution is as follows:

[0096] (1) Vanillyl acetone (30 g, 180.5 mmol) was dissolved in 150 mL of anhydrous DMF, and ethyl 4-bromobutyrate (31 mL, 217 mmol) and potassium carbonate (37.4 g, 271 mmol) were added in sequence. The mixture was stirred overnight under a nitrogen atmosphere. After the reaction was completed, the reaction solution was poured into 2 L of ice water for sedimentation, stirred at room temperature for 2 h, and allowed to stand at 4 °C overnight. The precipitate was filtered and vacuum dried to obtain intermediate 1 (ethyl 4-(4-acetyl-2-methoxyphenoxy)butyrate) with a yield of 95%.

[0097] (2) Intermediate 1 (25 g, 89 mmol) was added in batches to 70 mL of 70% concentrated nitric acid pre-cooled in an ice bath, with the temperature controlled not to exceed 35°C. After reacting at 32°C for 1 h, the mixture was added dropwise to 4°C deionized water for precipitation. The mixture was stirred, allowed to stand, and filtered to obtain intermediate 2 (nitration product). The mixture was recrystallized from ethanol to obtain a light yellow solid with a yield of 60%.

[0098] (3) Intermediate 2 (6.36 g, 19.5 mmol) was dissolved in ethanol (100 mL). After bubbling nitrogen at 38°C, sodium borohydride (0.459 g, 12.1 mmol) was slowly added and stirred overnight to obtain a red solution. After sedimentation and filtration, yellow powder intermediate 3 (reduction product) was obtained with a yield of 62%.

[0099] (4) Intermediate 3 (3.58 g, 10.9 mmol) was dissolved in 15 mL of anhydrous pyridine and azeotropically dehydrated. The mixture was then dissolved in 30 mL of anhydrous DCM (dichloromethane), and CDI (2.66 g, 16.4 mmol) was added. The mixture was stirred at room temperature in the dark for 2.5 h, and then dopamine hydrochloride (6.22 g, 32.8 mmol) and triethylamine (5.32 mL, 38.3 mmol) were added. The mixture was reacted in 20 mL of anhydrous DMF for 24 h. The solvent was removed by rotary evaporation, and the mixture was purified by silica gel column chromatography (methanol / DCM = 1:4) to obtain an orange solid intermediate 4 (amide coupling product) with a yield of 66%.

[0100] (5) Intermediate 4 (4.89 g, 9.7 mmol) and sodium hydroxide (0.57 g, 14.5 mmol) were dissolved in EtOH / H2O (3:1, 50 mL), stirred at room temperature overnight, and the solvent was removed by rotary evaporation. The mixture was redissolved in water and the pH was adjusted to ~4. The mixture was centrifuged and washed to obtain brown solid intermediate 5 (o-nitrobenzyl dopamine photosensitive small molecule o-NB-DA) with a yield of 60%.

[0101] (6) PEG (Mn = 6000, 10 g, 1.66 mmol) and triethylamine (5.54 mL, 40 mmol) were dissolved in 120 mL of anhydrous DCM and stirred in an ice bath. Methanesulfonyl chloride (3.6 mL, 46.5 mmol) was dissolved in 40 mL of anhydrous DCM and slowly added at a rate of 2 h. The reaction was continued in an ice bath for 48 h. After the reaction, deionized water and DCM (100 mL:40 mL) were added. The phases were separated using a separatory funnel. The organic phase was washed with 1N HCl and saturated NaCl in sequence. After drying and settling, PEG-SO2CH3 (9.7 g) was obtained with a yield of 97%.

[0102] (7) PEG-SO2CH3 was dissolved in 300 mL of concentrated ammonia water, and ammonium chloride (35.5 g, 663.8 mmol) was added. The mixture was reacted at room temperature for 48 h. NaCl (36 g) was added and the mixture was extracted with DCM. The organic phase was dried and precipitated to obtain PEG-NH2 (9.5 g) with a yield of 95%.

[0103] (8) Intermediate 5 (2.65 g, 5.54 mmol) was dissolved in 20 mL of anhydrous DMF, and HBTU (2.1 g, 5.54 mmol) and DIPEA (0.96 mL, 5.54 mmol) were added. PEG-NH2 (10.13 g, 1.68 mmol) was dissolved in 10 mL of DMF and slowly added to the reaction solution. The reaction was allowed to react at room temperature for 48 h. The reaction solution was diluted with DCM and washed with saturated NaHCO3, 1N HCl, and saturated NaCl solutions in sequence. After drying and concentration, a yellow solid was precipitated. The solid was dissolved in deionized water and dialyzed for 3 days (MWCO = 3500). Finally, it was freeze-dried to obtain PEG-o-NB-DA (9.5 g, Mw = 6000) with a yield of 95%.

[0104] (9) Weigh 200 mg of PEG-o-NB-DA and add it to 0.9 mL of PBS buffer. Vortex and mix thoroughly to dissolve it completely, forming a viscous, transparent macromolecular monomer solution, which is the PEG-o-NB-DA hydrogel prepolymer solution.

[0105] Example 2

[0106] A method for preparing a device that can be light-controlled and detached, specifically an electrocortico-gyroscope (ECoG) electrode containing gel, is to transfer a SU-8 patterned electrode to a silicon wafer surface, using the same processing method as in Example 1, specifically comprising the following steps:

[0107] (1) Ecoflex 00-30 (A:B = 1:1) was used as the substrate layer, which was degassed and spin-coated onto the PVA sacrificial layer to form an ultra-flexible film with a thickness of 100 μm.

[0108] (2) PEDOT:PSS / EG (ethylene glycol) conductive solution was deposited on the electrode channel area by spraying, with a surface impedance of 800Ω·cm 2 ;

[0109] (3) 10 wt % PEDOT:PSS nanofibers and 0.5 wt % LiCl were added to the 25 wt % PEG-COU-PCA (containing coumarin and protocatechuic acid) hydrogel prepolymer to improve the conductivity;

[0110] (4) The porous structure gel layer (pore size 5-20 μm) was evenly coated by spraying (0.2 MPa, spray distance 15 cm).

[0111] UV light (365nm, 10mW / cm 2 ) to test its gel-sol transition ability and verify the controllable debonding effect.

[0112] Wherein, the preparation method of PEG-COU-PCA hydrogel prepolymer solution is:

[0113] (1) 4-Hydroxycoumarin (6.0 g, 33.3 mmol) was dissolved in 100 mL of anhydrous DMF, 4-bromobutyric acid (4.5 mL, 39.6 mmol) and potassium carbonate (6.0 g, 43.5 mmol) were added, and the mixture was stirred at room temperature under nitrogen atmosphere for 24 h. The reaction solution was poured into 300 mL of ice water for precipitation, filtered, and dried to obtain a light yellow solid intermediate 1 (4-hydroxycoumarin butyrate) with a yield of 88%.

[0114] (2) Intermediate 1 (3.0 g, 11 mmol) and protocatechuic acid (PCA, 3.4 g, 20 mmol) were dissolved in 50 mL of anhydrous DMF. EDC·HCl (3.8 g, 19.8 mmol), NHS (2.3 g, 19.8 mmol) and triethylamine (3.0 mL, 21.5 mmol) were added and reacted at room temperature in the dark for 24 h. The reaction solution was evaporated to remove the solvent and purified by silica gel column chromatography (ethyl acetate / petroleum ether 1:3) to obtain orange solid intermediate 2 (COU-PCA).

[0115] (3) PEG (Mn = 6000, 10 g, 1.66 mmol) and triethylamine (5.54 mL, 40 mmol) were dissolved in 120 mL of anhydrous DCM and stirred in an ice bath. Methanesulfonyl chloride (3.6 mL, 46.5 mmol) was dissolved in 40 mL of anhydrous DCM and slowly added dropwise to the PEG solution. Stirring in an ice bath was continued for 48 h. After the reaction was completed, deionized water and DCM (100 mL:40 mL) were added, the mixture was separated, and washed with 1N HCl and saturated NaCl solution in sequence. The organic phase was dried and rotary evaporated to obtain PEG-SO2CH3 (9.7 g) with a yield of 97%.

[0116] (4) PEG-SO2CH3 was dissolved in 300 mL of concentrated ammonia water, and ammonium chloride (35.5 g, 663.8 mmol) was added. The mixture was reacted at room temperature for 48 h. After adding NaCl (36 g), the mixture was extracted with DCM. The organic phase was dried and concentrated by rotary evaporation to obtain PEG-NH2 (9.5 g) with a yield of 95%.

[0117] (5) Intermediate 2 (COU-PCA, 2.65 g, 5.54 mmol) was dissolved in 20 mL of anhydrous DMF, and HBTU (2.1 g, 5.54 mmol) and DIPEA (0.96 mL, 5.54 mmol) were added and mixed for 10 min for activation. PEG-NH2 (10.13 g, 1.68 mmol) was then dissolved in 10 mL of DMF and slowly added dropwise to the reaction mixture. The mixture was stirred at room temperature for 48 h to complete the condensation reaction.

[0118] (6) The reaction solution was diluted with DCM, washed with saturated NaHCO3, 1N HCl, and saturated NaCl solutions, dried, and concentrated to obtain a light yellow solid. The solid was dissolved in deionized water, dialyzed with a MWCO 3500 dialysis bag for 3 days, with the water changed 4 times per day, and freeze-dried to obtain the PEG-COU-PCA macromonomer (yield approximately 90%).

[0119] (7) Weigh 200 mg of PEG-COU-PCA macromer and add it to 0.9 mL of PBS buffer (pH 7.4). Vortex and mix at room temperature until completely dissolved to obtain a viscous, transparent hydrogel prepolymer solution, which is the PEG-COU-PCA hydrogel prepolymer solution.

[0120] Example 3

[0121] A method for preparing a device that can be light-controlled and detached, specifically an electrocortico-gauge (ECoG) electrode containing gel, comprises the following steps:

[0122] (1) A medical polyurethane (PU) film was used instead of the PDMS substrate and adhered to the SU-8 electrode pattern by hot pressing;

[0123] (2) The thickness of the PVA sacrificial layer is controlled at 20 μm to ensure that the PU can be completely demolded after molding;

[0124] (3) The electrode material is 100 μm silver wire, embedded in the preset groove on the PU surface, and encapsulated with PU prepolymer liquid at the pin;

[0125] (4) 1 wt % gold nanoparticles (AuNPs, particle size ≈ 30 nm) were added to the hydrogel to enhance the charge injection capacity of the electrode interface;

[0126] (5) The hydrogel prepolymer solution was made of 20 wt% POEGMA-AZO-DA (AZO is azobenzene group), PBS was used as the dispersion medium, and the cross-linking time was 5 min.

[0127] The obtained electrodes were tested on the surface of mouse brains, and the signal acquisition was stable, and they could be non-invasively peeled off after UV light exposure.

[0128] The preparation method of POEGMA-AZO-DA hydrogel prepolymer solution is as follows:

[0129] (1) Weigh p-nitroaniline (4.2 g, 30.4 mmol) and hydrochloric acid (12 mL, 37%), mix them in an ice bath and cool to 0°C. Then, add sodium nitrite aqueous solution (2.2 g, 32 mmol dissolved in 10 mL H2O) dropwise and stir for 30 min to generate the diazonium salt. This diazonium salt solution is slowly added dropwise to an ice-cold solution containing aniline (3.0 g, 32 mmol) and sodium acetate (5.2 g, 63.4 mmol) at 0°C and stirred for 2 h. The reaction generates azobenzene intermediate A (4-(phenylazo)aniline), which is filtered and washed with ethanol with a yield of 70%.

[0130] (2) Intermediate A (4.0 g, 20 mmol) was dissolved in 50 mL of anhydrous DMF, and CDI (3.2 g, 19.7 mmol) was added and stirred at room temperature for 1.5 h to activate the carbonyl group; dopamine hydrochloride (5.0 g, 26.4 mmol) and TEA (4.0 mL, 28.7 mmol) were added and the reaction was continued for 24 h to obtain intermediate B (AZO-DA small molecule) with a yield of about 68%, which could be purified by column chromatography;

[0131] (3) Weigh POEGMA-NH2 (Mn≈8000, 10 g, 1.25 mmol) and dissolve it in 100 mL of anhydrous DMSO for later use; POEGMA-NH2 can be prepared from POEGMA-Br by aminolysis or Gabriel reaction;

[0132] (4) Intermediate B (1.5 g, 3 mmol) was dissolved in 15 mL of DMF, and HBTU (1.1 g, 2.9 mmol) and DIPEA (0.5 mL, 2.9 mmol) were added for pre-activation for 10 min. The mixture was then slowly added dropwise to the POEGMA-NH2 solution and reacted at room temperature for 48 h to complete the amide coupling.

[0133] (5) The reaction solution was diluted and washed with 1N HCl, saturated NaHCO3, and saturated NaCl in sequence, extracted with DCM, dried, and rotary evaporated to obtain a yellow solid; dissolved in deionized water, dialyzed using a MWCO 3500 dialysis bag for 3 days, and freeze-dried to obtain the POEGMA-AZO-DA macromonomer with a yield of approximately 85%;

[0134] (6) Weigh 200 mg of POEGMA-AZO-DA macromer and add it to 0.9 mL of PBS buffer. Vortex and mix to fully dissolve it to form a transparent viscous prepolymer solution, which is the final POEGMA-AZO-DA hydrogel prepolymer solution, which can be used for photoresponsive hydrogel crosslinking.

[0135] Example 4

[0136] A method for preparing a device that can be light-controlled and detached, specifically an electrocortico-gauge (ECoG) electrode containing gel, comprises the following steps:

[0137] (1) A PLGA film (thickness ≈ 100 μm) was hot-pressed onto the SU-8 patterned layer to construct a biodegradable substrate;

[0138] (2) The electrode part uses a magnesium (Mg) film (thickness 300 nm) prepared by vapor deposition and covered with a layer of PLGA (20 nm) to regulate its degradation rate;

[0139] (3) Using 30 wt% PCL-PEG-oNB-PCA (PCA is protocatechuic acid) hydrogel prepolymer solution, 0.1 wt% carboxylated carbon nanotubes (CNT-COOH) were added to improve conductivity;

[0140] (4) The gel was spin-coated to a thickness of 50 μm and the cross-linking time was 4 min.

[0141] This device design is suitable for degradable neural interfaces that do not require secondary removal after surgery.

[0142] The preparation method of PCL-PEG-oNB-PCA hydrogel prepolymer solution is as follows:

[0143] (1) Synthesis of o-nitrobenzyl ester-protocatechuic acid small molecule (oNB-PCA): Vanillyl ethyl ketone (30 g, 180.5 mmol) was dissolved in 150 mL of anhydrous DMF, and ethyl 4-bromobutyrate (31 mL, 217 mmol) and potassium carbonate (37.4 g, 271 mmol) were added in sequence. The mixture was stirred overnight under nitrogen protection. The reaction solution was poured into 2 L of ice water for precipitation, stirred at room temperature for 2 h, and then allowed to stand at 4 °C overnight. The mixture was filtered and dried to obtain intermediate 1 with a yield of about 95%.

[0144] (2) Intermediate 1 (25 g, 89 mmol) was slowly added to pre-cooled 70% nitric acid (70 mL), reacted in an ice bath for 1 h (<35°C), then added dropwise to ice water for precipitation, filtered and recrystallized to obtain intermediate 2 with a yield of 60%;

[0145] (3) Intermediate 2 (6.36 g, 19.5 mmol) was dissolved in 100 mL of anhydrous ethanol. After bubbling nitrogen, sodium borohydride (0.459 g, 12.1 mmol) was slowly added. The mixture was reacted at 38°C overnight and filtered to obtain the yellow intermediate 3 with a yield of 62%.

[0146] (4) Intermediate 3 (3.58 g, 10.9 mmol) was dissolved in 30 mL of DCM, and CDI (2.66 g, 16.4 mmol) was added. The mixture was reacted at room temperature in the dark for 2.5 h. Protocatechuic acid (PCA, 3.0 g, 16.4 mmol) and TEA (2.5 mL, 18 mmol) were added and the reaction was continued in DMF for 24 h. The oNB-PCA small molecule building block, intermediate 4, was purified by column chromatography with a yield of approximately 65%.

[0147] (5) Synthesis of PCL-PEG block copolymer and terminal amination: The hydroxyl-terminated PCL-PEG copolymer (PCL2000-PEG2000, 5.0 g) was dissolved in anhydrous DCM, and methanesulfonyl chloride (1.0 mL) and TEA (1.5 mL) were added. The mixture was reacted at room temperature for 24 h to obtain PCL-PEG-SO2CH3. Concentrated ammonia and ammonium chloride were then added and reacted in an ice bath for 48 h. After extraction with DCM and drying, PCL-PEG-NH2 was obtained with a yield of 85%.

[0148] (6) Synthesis of PCL-PEG-oNB-PCA macromonomer: oNB-PCA (1.5 g, 3.3 mmol) obtained in step (4) was dissolved in DMF (20 mL), and activated with HBTU (1.25 g, 3.3 mmol) and DIPEA (0.57 mL, 3.3 mmol) for 10 min; the mixture was slowly added dropwise to a DMF solution containing PCL-PEG-NH2 (5.0 g, 1.1 mmol) and reacted at room temperature for 48 h;

[0149] (7) The reaction solution was diluted and washed with saturated NaHCO3, 1N HCl, and saturated NaCl in sequence. The organic phase was concentrated by rotary evaporation. The product was dissolved in deionized water, dialyzed (MWCO 3500) for 3 days, and then freeze-dried to obtain PCL-PEG-oNB-PCA macromonomer with a yield of approximately 90%;

[0150] (8) Preparation of hydrogel prepolymer solution: Weigh 200 mg of PCL-PEG-oNB-PCA macromer, add it to 0.9 mL of PBS buffer (pH 7.4), and shake until completely dissolved to form a transparent and viscous hydrogel prepolymer solution, which can be used for subsequent oxidative cross-linking reactions.

[0151] Example 5

[0152] A method for preparing a device that can be light-controlled and detached, specifically an electrocortico-gauge (ECoG) electrode containing gel, comprises the following steps:

[0153] (1) The substrate is made of PVDF film (thickness 120 μm), which has a certain piezoelectric response capability;

[0154] (2) The electrode pattern was generated by laser etching of laser-induced graphene (LIG) on the PVDF surface;

[0155] (3) 10 wt% PEDOT:PSS + 15 wt% Galinstan liquid metal droplets (particle size 3 μm) were blended into 60 wt% PEG-COU-Catechin hydrogel prepolymer to form a composite conductive network;

[0156] (4) The gel layer is deposited by spraying to form a 30 μm thin layer with good flexibility and interface packaging.

[0157] After being bent 1000 times, there is no significant increase in electrode resistance, verifying the mechanical stability and adhesion reliability.

[0158] The preparation method of PEG-COU-Catechin hydrogel prepolymer solution is as follows:

[0159] (1) Synthesis of 4-hydroxycoumarin butyrate intermediate: 4-hydroxycoumarin (6.0 g, 33.3 mmol) was dissolved in 100 mL of anhydrous DMF, 4-bromobutyric acid (4.5 mL, 39.6 mmol) and potassium carbonate (6.0 g, 43.5 mmol) were added, and the mixture was stirred at room temperature under nitrogen atmosphere for 24 h. After the reaction, the reaction solution was poured into 300 mL of ice water to precipitate a light yellow precipitate, which was filtered, washed and vacuum dried to obtain 4-hydroxycoumarin butyrate intermediate A with a yield of about 88%.

[0160] (2) Synthesis of COU-Catechin coupling small molecule: Intermediate A (3.0 g, 11 mmol) and catechin (5.0 g, 17.7 mmol) were dissolved in 50 mL of anhydrous DMF, and EDC·HCl (3.8 g, 19.8 mmol), NHS (2.3 g, 19.8 mmol) and triethylamine (3.0 mL, 21.5 mmol) were added. The mixture was reacted at room temperature for 24 h in the dark. The solvent was removed by rotary evaporation, and the crude product was purified by silica gel column chromatography (DCM / MeOH = 20:1 to 5:1) to obtain orange solid intermediate B (COU-Catechin coupling product) with a yield of about 70%.

[0161] (3) PEG-NH2 carboxylate coupling: Weigh four-arm polyethylene glycol amino (four-arm PEG-NH2, Mn≈10,000 Da, 10 g, 1.0 mmol) and dissolve it in 100 mL of anhydrous DMSO. Stir magnetically to dissolve it completely. Separately, take intermediate B (1.5 g) and dissolve it in 20 mL of DMF. Add HBTU (1.1 g, 2.9 mmol) and DIPEA (0.5 mL, 2.9 mmol) and activate it for 10 min. Then, slowly add it dropwise to the PEG-NH2 solution. The mixture is stirred in the dark at room temperature for 48 h.

[0162] (4) Purification and drying: The reaction system was diluted with DCM, and the organic phase was washed sequentially with 1N HCl, saturated NaHCO3, and saturated NaCl solutions; dehydrated with a desiccant and concentrated by rotary evaporation to obtain a yellow solid; the product was dissolved in deionized water and dialyzed using a dialysis bag with a MWCO of 3500 for 3 days (changing the water 4 times per day), and freeze-dried to obtain the PEG-COU-Catechin macromonomer with a yield of approximately 85%;

[0163] (5) Preparation of hydrogel prepolymer solution: Weigh 200 mg of PEG-COU-Catechin macromolecular monomer and add it to 0.9 mL of PBS buffer (pH 7.4). Vortex and mix until completely dissolved to form a transparent and uniform hydrogel prepolymer solution, which can be used for the subsequent oxidative cross-linking reaction of catechol groups to form a functional hydrogel with photoresponsive and adhesive properties.

[0164] Performance Testing

[0165] 1. Electrochemical impedance spectroscopy test

[0166] Based on Example 1, the ECoG electrode was subjected to electrochemical impedance spectroscopy (EIS) testing using a three-electrode system with a frequency range of 0.1 Hz to 100 kHz. The results are as follows: Figure 4 shown.

[0167] Depend on Figure 4The impedance amplitude is less than 500Ω at 1kHz; the phase angle changes smoothly, with distinct capacitive characteristics; and the interfacial charge transfer impedance (Rct) in the Nyquist plot is approximately 150Ω. These results demonstrate that the gel-integrated layer possesses excellent ionic / electronic coupling and conduction capabilities, meeting the requirements for EEG signal transmission.

[0168] 2. Linear voltammetry and resistivity evaluation

[0169] Based on Example 1, linear voltammetry and resistivity evaluation were performed on the ECoG electrodes. Linear sweep voltammetry (LSV) testing was performed in PBS using a two-electrode method. The current response was linear and the slope was stable over the voltage range of -0.5 V to +0.5 V. The surface resistivity of the material was calculated using Ohm's law: ρ ≈ 9.5 Ω·m in the electrode channel direction.

[0170] Figure 5 The test curve and resistivity calculation results are shown, indicating that the silver wire-gel contact area has good conductivity.

[0171] 3. Cyclic voltammetry (CV) test and charge storage capacity evaluation

[0172] Based on Example 1, the ECoG electrode was subjected to cyclic voltammetry (CV) testing and charge storage capacity evaluation. The CV test was performed in the range of -0.5 V to +0.5 V at a scan rate of 50 mV / s. The charge storage capacity (CSC) was calculated to be approximately: CSC ≈ 10.3 mC / cm 2 .

[0173] The results (see Figure 6 ) is significantly higher than that of traditional Pt electrodes (generally 1-5mC / cm 2 ), indicating that it has higher capacitive coupling ability, which helps to improve the resolution of neural signals.

[0174] 4. Constant current charge and discharge test

[0175] Based on Example 1, the ECoG electrode was subjected to a constant current charge and discharge test at 0.5 mA / cm 2 The current density was tested for 1000 times with constant current charge and discharge (GCD) and the charge and discharge curves were recorded. Figure 7 shown.

[0176] Depend on Figure 7 It can be seen that the first charge capacity is 17mC / cm 2 After 1000 times, the charge retention rate remained at 94.5%, which was a good value. There was no obvious polarization phenomenon, indicating that the electrode structure had excellent stability under multiple uses.

[0177] 5. Electrophysiological signal acquisition and verification

[0178] On the basis of Example 1, the electrophysiological signal acquisition and verification were performed using ECoG electrodes. The prepared ECoG electrodes were implanted into the cerebral cortex of SD rats to record spontaneous potential signals. The results were as follows: Figure 8 shown.

[0179] Depend on Figure 8 It can be seen that the channel signal amplitude is clear; the Pearson correlation analysis between channels shows that the R value of adjacent channels is ~0.7, which has high spatial consistency.

[0180] 6. Rat visual stimulation test

[0181] Based on Example 1, visual stimulation (frequency 8 Hz) was performed on rats implanted with ECoG electrodes, and SSVEP signals were recorded and FFT transformed. The results are as follows: Figure 9 shown.

[0182] Depend on Figure 9 It can be seen that the power spectral density is significantly enhanced at the target frequency; the peak signal-to-noise ratio reaches 12dB, and external stimuli can be clearly distinguished; this shows that this electrode has good external event response and analysis capabilities and can be used in closed-loop brain-computer systems.

[0183] 7. In vivo on-demand debonding test

[0184] Based on Example 1, ECoG electrodes were implanted on the surface of the brain of SD rats for 10 days, and then an in vivo on-demand debonding test was performed using 365nm UV light. The results are as follows:

[0185] The electrode was peeled off without damage within 3 minutes after illumination, and no obvious mechanical traction was observed. The tissue was removed for GFAP and Iba-1 immunofluorescence staining. Figure 10 There was no significant difference in inflammatory response between the light-exposed group and the non-implanted control group, indicating that the debonding process did not cause obvious tissue damage.

[0186] The above description of the disclosed embodiments is intended to enable one skilled in the art to implement or use the present invention. Various modifications to these embodiments will be readily apparent to one skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention is not limited to the embodiments shown herein but is intended to conform to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A light-controlled detachable device, characterized in that: It includes a flexible base layer, an electrode layer and a gel integration layer; The flexible base layer is made of a silicon-based elastic polymer material; The electrode layer is composed of a patterned conductive material and is embedded in the flexible base layer; The gel integration layer is composed of a light-responsive adhesive hydrogel with electrical conductivity and covers the surfaces of the electrode layer and the flexible base layer.

2. The light-controlled detachable device according to claim 1, characterized in that: The silicon-based elastic polymer material is at least one of two-component room temperature curing silicone rubber, medical silicone, medical polyurethane, polylactic acid-glycolic acid copolymer, polycaprolactone, polyvinylidene fluoride and its copolymer and polyvinyl alcohol-polyacrylic acid interpenetrating network material.

3. The light-controlled detachable device according to claim 1, characterized in that: The patterned conductive material is at least one of gold, platinum, platinum-iridium alloy, magnesium, zinc, poly(3,4-ethylenedioxythiophene)-polystyrene sulfonic acid, graphene, carbon nanotube film, laser-induced graphene and gallium-indium-tin alloy.

4. The light-controlled detachable device according to claim 1, characterized in that: The photoresponsive adhesive hydrogel is formed by polymerizing macromonomers containing photo-controlled bond-breaking units; The macromonomer containing the light-controlled cleavage bond unit is composed of a polymer chain, a light-responsive cleavage functional group and a molecular fragment containing a catechol structure covalently connected through chemical bonds.

5. The light-controlled detachable device according to claim 4, characterized in that: The polymer chain is at least one of polyethylene glycol, polyoxyethylene-polyoxypropylene-polyoxyethylene block copolymer, poly(polyethylene glycol methacrylate), polycaprolactone-polyethylene glycol block copolymer, poly(lactic acid-glycolic acid)-polyethylene glycol block copolymer, and poly(lactic acid-glycolic acid)-polyethylene glycol-poly(lactic acid-glycolic acid) triblock copolymer; The photoresponsive cleavage functional group is at least one of o-nitrobenzyl ester, coumarin, anthracene, thymine and O-acyl oxime; The molecular fragment containing catechol structure is at least one of dopamine, catechin, epicatechin, protocatechuic acid, catecholamine and tannic acid.

6. The light-controlled detachable device according to claim 4, characterized in that: The photoresponsive adhesive hydrogel further comprises a conductive substance, which is at least one of a conductive polymer, a carbon-based filler, a metal nanoparticle, an ion conductive medium and a composite conductive network.

7. A method for preparing a device capable of light-controlled detachment according to any one of claims 1 to 6, characterized in that: The specific steps include: (1) Electrode patterns were formed on a silicon wafer by photolithography, and then oxygen plasma treatment was performed to prepare a hydrophilic surface; (2) spin coating a water-soluble polymer solution on the surface of the electrode pattern to form a sacrificial layer; (3) spin coating the silicone rubber prepolymer on the sacrificial layer and curing it to form a flexible base layer; (4) dissolving the sacrificial layer with water to achieve demolding, and embedding a patterned conductive material on the surface to form an electrode layer; (5) Applying the photoresponsive adhesive hydrogel prepolymer solution on the surface of the electrode layer and the flexible substrate layer, and curing the solution through cross-linking to form a gel integration layer, thereby obtaining the photo-controllable detachable device.

8. The method for preparing a light-controlled detachable device according to claim 7, characterized in that: In step (5), the preparation method of the photoresponsive adhesive hydrogel prepolymer solution is: 1) Synthesizing intermediate A containing a photoresponsive cleavage functional group; 2) coupling the intermediate A with a molecular fragment containing a catechol structure to obtain a photosensitive adhesion small molecule structural unit B; 3) coupling the photosensitive adhesive small molecule structural unit B with the polymer chain containing active functional groups in a solvent under the catalytic action of a condensation agent to obtain a macromonomer containing a photo-controlled bond-breaking unit; The condensing agent is at least one of 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate / N,N-diisopropylethylamine, 1-ethyl-(3-dimethylaminopropyl)carbodiimide / N-hydroxysuccinimide, N,N'-dicyclohexylcarbodiimide / 1-hydroxybenzotriazole, 1,1'-carbonyldiimidazole and triphosgene; the solvent is at least one of N,N-dimethylformamide, dimethyl sulfoxide and N-methylpyrrolidone; 4) dissolving the macromonomer containing the photo-scissile bond in a dispersion medium to obtain the photoresponsive adhesive hydrogel prepolymer solution; The dispersion medium is PBS buffer solution with a concentration of 10 mM, containing 0.15 M NaCl and a pH of 7.4, physiological saline or simulated cerebrospinal fluid.

9. The method for preparing a light-controlled detachable device according to claim 7, characterized in that: In step (5), the coating is performed by spin coating or spray coating; The spin coating method has a rotation speed of 1000-2000 rpm and the gel thickness is controlled at 20-100 μm; The spray gun air pressure of the spraying method is 0.1-0.3 MPa, the spraying distance is 10-20 cm, and a gradient pore structure with a pore size of 5-50 μm is formed; The oxidant selected for the cross-linking curing is sodium periodate, ferric chloride or H2O2 / HRP.

10. Use of a light-controllable detachable device as claimed in any one of claims 1 to 6 or a light-controllable detachable device prepared by the preparation method as claimed in any one of claims 7 to 9 in constructing an implantable brain-computer interface system.

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