Flexible electrode devices, methods of making and using the same

Abstract

This application relates to flexible electrode devices, their fabrication methods, and applications. The fabrication method involves: molding medical-grade silicone to form a flexible substrate; using liquid metal as a raw material, screen printing and curing are performed on the surface of the flexible substrate to form a conductive network; after the conductive network is connected to a circuit, it is encapsulated with food-grade silicone adhesive while retaining predetermined electrode sites; the predetermined electrode sites are wetted with a pretreatment solution, and then a hydrogel prepolymer is placed on the predetermined electrode sites and photocured to form electrodes; wherein the pretreatment solution is a mixed solution of benzophenone and a silane coupling agent, and the solvent in the pretreatment solution is toluene; the solvent interaction parameter between the medical-grade silicone, the food-grade silicone adhesive, and the toluene in the pretreatment solution is 0.4~0.5. In this flexible electrode device, the hydrogel electrode, the conductive network, and the flexible substrate are covalently cross-linked, resulting in excellent conductivity stability and high reliability.

Description

Technical Field

[0001] This application relates to the field of biomedical electrical stimulation technology, and in particular to a flexible electrode device, its preparation method, and its application. Background Technology

[0002] With the development of scalp electrical stimulation hair growth technology, the market has put forward higher requirements for the wearing comfort, signal transmission stability and electrode firmness of electrode caps. However, traditional electrode caps still have many problems: (1) Traditional electrode caps are made of hydrogel electrodes that are physically adsorbed and attached to the surface of elastic base (such as silicone, elastic cloth). During long-term wear, they are prone to displacement or even falling off due to scalp oil, sweat or head movements (such as bending down or turning the head), which will disrupt the continuity of electrical stimulation; (2) The metal wire and hydrogel electrode are mechanically connected. The contact resistance between the wire and the gel is large. Repeated deformation can easily lead to wire breakage. Moreover, ion migration is easy to occur at the interface between metal and hydrogel, which will affect the stability of conductivity; (3) The base of traditional electrode caps is mostly planar, which cannot fit the curved surface of the scalp. Some elastic materials (such as latex) are prone to allergies when in contact with the scalp for a long time; In animal experiments (such as electrical stimulation of the back of mice to promote hair growth), the existing electrodes are mostly independent patches that need to be fixed with tape. They are easy to fall off due to scratching by the animals and cannot simulate the scene of synchronous stimulation of multiple areas. Summary of the Invention

[0003] Based on this, it is necessary to provide a flexible electrode device, its preparation method, and its application to address the above-mentioned problems. In the flexible electrode device described in this application, the hydrogel electrode, the conductive network, and the flexible substrate are covalently cross-linked, resulting in excellent conductivity stability and high reliability of the flexible electrode device.

[0004] A method for fabricating a flexible electrode device includes the following steps:

[0005] Medical-grade silicone is molded to form a flexible substrate;

[0006] Using liquid metal as raw material, a conductive network is formed by screen printing and curing on the surface of a flexible substrate.

[0007] After connecting the conductive network to the circuit, it is encapsulated with food-grade silicone adhesive and the preset electrode sites are retained.

[0008] The preset electrode sites are wetted with a pretreatment solution, and then the hydrogel prepolymer is placed on the preset electrode sites and photocured to form electrodes.

[0009] The pretreatment solution is a mixed solution of benzophenone and silane coupling agent, and the solvent in the pretreatment solution is toluene. The solvent interaction parameter between medical grade silicone and toluene in the pretreatment solution is 0.4~0.5, and the solvent interaction parameter between food grade silicone adhesive and toluene in the pretreatment solution is 0.4~0.5.

[0010] In one embodiment, the surface tension of the liquid metal is 0.5 N / m to 0.7 N / m;

[0011] And / or, the electrical conductivity of liquid metal is 3 × 10⁻⁶. 4 S / cm ~4×10 4 S / cm;

[0012] And / or, the bonding strength between liquid metal and medical-grade silicone is 0.8 N / cm to 1.2 N / cm;

[0013] And / or, the liquid metal is selected from at least one of gallium indium alloy, gallium indium tin alloy, gallium indium tin silver alloy, gallium indium tin bismuth alloy, and gallium indium tin zinc alloy.

[0014] In one embodiment, after the impregnation treatment, the swelling degree of the medical-grade silicone at the preset electrode site is 5% to 10%.

[0015] In one embodiment, the molar ratio of the benzophenone to the silane coupling agent is 1:10 to 10:1;

[0016] And / or, the total concentration of benzophenone and silane coupling agent in the pretreatment solution is 1wt%~20wt%;

[0017] And / or, the silane coupling agent is selected from one of aminosilane coupling agents, acryloyloxysilane coupling agents, methacryloxysilane coupling agents, and mercaptosilane coupling agents.

[0018] In one embodiment, the molding process includes hot melt molding.

[0019] In one embodiment, the hydrogel prepolymer includes a hydrogel monomer, a conductive material, a crosslinking agent, a photoinitiator, and a solvent.

[0020] In one embodiment, the photocuring wavelength is 360nm~370nm, and the intensity is 20mW / cm². 2 ~30mW / cm 2 The duration is 90s~120s.

[0021] In one embodiment, the photocuring process further includes dialysis.

[0022] A flexible electrode device prepared by the method described above includes a flexible substrate and an encapsulation layer stacked together; a conductive network is provided between the flexible substrate and the encapsulation layer; the encapsulation layer has a through-hole structure, and a hydrogel electrode passes through the through-hole structure and communicates with the conductive network.

[0023] A bioelectric stimulation device, comprising the flexible electrode device as described above.

[0024] The preparation method described in this application utilizes a specific pretreatment solution to pretreat the preset electrode sites on a flexible substrate, which serves as a common anchoring platform. This allows the ends of the conductive network to be "embedded" when the hydrogel electrode is polymerized in situ on the flexible substrate. This not only helps to eliminate resistance fluctuations at the metal-gel interface and ensure the stability and accuracy of the electrical stimulation signal, but also constructs a four-layer heterogeneous synergistic integrated architecture of "substrate-circuit-encapsulation-electrode" through chemical-level integration. This architecture can meet the requirements of low-loss and high-efficiency signal transmission, while fundamentally solving the problem of electrode detachment and improving the reliability of flexible electrode devices. Detailed Implementation

[0025] To facilitate understanding of this application, it will be described in more detail below. However, it should be understood that this application can be implemented in many different forms and is not limited to the embodiments or examples described herein. Rather, these embodiments or examples are provided to provide a more thorough and complete understanding of the disclosure of this application.

[0026] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used herein in the specification of this application is for the purpose of describing particular implementations or embodiments only and is not intended to be limiting of this application. The optional range of the term "and / or" as used herein includes any one of two or more of the related listed items, as well as any and all combinations of the related listed items, including any two related listed items, any more related listed items, or a combination of all related listed items. In this application, when numerical ranges are involved, unless otherwise specified, the numerical ranges are considered continuous and include the minimum and maximum values ​​of the range, and every value between such minimum and maximum values. Further, when a range refers to an integer, it includes every integer between the minimum and maximum values ​​of the range. Furthermore, when multiple ranges are provided to describe a feature or characteristic, the ranges may be merged. In other words, unless otherwise specified, all ranges disclosed herein should be understood to include any and all sub-ranges to which they are incorporated.

[0027] This application provides a method for fabricating a flexible electrode device, comprising the following steps:

[0028] Medical-grade silicone is molded to form a flexible substrate;

[0029] Using liquid metal as raw material, a conductive network is formed by screen printing and curing on the surface of a flexible substrate.

[0030] After connecting the conductive network to the circuit, it is encapsulated with food-grade silicone adhesive and the preset electrode sites are retained.

[0031] The preset electrode sites are wetted with a pretreatment solution, and then the hydrogel prepolymer is placed on the preset electrode sites and photocured to form electrodes.

[0032] The pretreatment solution is a mixed solution of benzophenone and silane coupling agent, and the solvent is toluene. The solvent in the toluene pretreatment solution is toluene. The solvent interaction parameter between medical grade silicone and toluene in the pretreatment solution is 0.4~0.5, and the solvent interaction parameter between food grade silicone adhesive and toluene in the pretreatment solution is 0.4~0.5.

[0033] It should be noted that the interaction parameter (Huggins parameter) is a parameter that reflects the change in the interaction energy when the polymer and solvent are mixed.

[0034] Considering that flexible electrode devices need to balance structural stability, flexibility, and long-term reliability, this application specifically uses a combination of medical-grade silicone as the substrate and food-grade silicone adhesive as the encapsulation layer. On the one hand, the elastic modulus of medical-grade silicone (PDMS) is about 0.5MPa~1.5MPa, and the elastic modulus of food-grade silicone adhesive is about 0.3MPa~2.0MPa. The moduli of the two are on the same order of magnitude, which is conducive to forming a "flexible-flexible" synergistic system. This matching avoids the stress concentration caused by excessive modulus difference in traditional "rigid substrate-flexible encapsulation" or "flexible substrate-rigid encapsulation". When the flexible electrode device moves with the scalp or bends the animal's body, the substrate and encapsulation layer can deform synchronously without the risk of peeling or cracking, thereby ensuring the long-term integrity of the circuit encapsulation. Furthermore, compared to traditional encapsulation materials (such as epoxy resin adhesive with a modulus > 10 MPa), food-grade silicone adhesives have low modulus characteristics and high compatibility with medical-grade silicone. They can also solve the problem of traditional rigid encapsulation layers falling off under flexible deformation, while ensuring the overall soft touch of flexible electrode devices and improving wearing comfort.

[0035] On the other hand, the core components of both medical-grade and food-grade silicone adhesives are siloxane polymers (-Si-O-), exhibiting high molecular homology. At the interface, molecular chains can interpenetrate and entangle, creating a dual effect of physical adsorption and chemical affinity. This homology results in a significantly stronger bond between the encapsulation layer and the substrate compared to combinations of dissimilar materials (such as a silicone substrate and an acrylic encapsulation layer), with a peel strength reaching 1.5 N / cm to 2.5 N / cm. This effectively avoids risks such as circuit oxidation and short circuits caused by encapsulation layer detachment. Furthermore, food-grade silicone adhesives possess both insulation and biocompatibility, releasing no toxic or harmful substances after curing. Together with the medical-grade silicone substrate, they form a biocompatible system, causing no irritation or allergies with long-term contact with the scalp or animal skin, making them suitable for various applications, including medical settings and animal experiments.

[0036] Based on this, this application specifically employs a particular pretreatment solution as the pretreatment system for the medical-grade silicone substrate and the food-grade silicone adhesive encapsulation layer. On one hand, the solvent interaction parameter between the medical-grade silicone and toluene in the pretreatment solution is 0.4~0.5, and the solvent interaction parameter between the food-grade silicone adhesive and toluene in the pretreatment solution is also 0.4~0.5. This facilitates the control of slight swelling of the silicone surface by the solvent, resulting in relaxed polymer chains and a loose interfacial structure. This controllable and mild swelling not only avoids damaging the bulk structure of the substrate and encapsulation layer, maintaining their structural integrity, but also provides permeation channels for benzophenone molecules, allowing them to fully penetrate and uniformly disperse on the substrate and encapsulation layer surfaces. Furthermore, toluene and benzophenone exhibit good compatibility, which helps ensure the stability of the pretreatment solution. This synergistic effect of toluene on the swelling of silicone ensures that benzophenone molecules are uniformly anchored on the substrate and encapsulation layer surfaces, laying the foundation for subsequent covalent cross-linking.

[0037] On the other hand, benzophenone, as a photosensitizer, under 360nm~370nm light excitation, can not only initiate the polymerization of hydrogel monomers in the hydrogel prepolymer to form a hydrogel network, but also cause benzophenone molecules to transition from the ground state to the excited state, capturing hydrogen atoms from the silica gel surface and generating free radical active sites (-Si-CH2·). This transforms the originally hydrophobic and inert silica gel interface into an active interface. Combined with swelling, this promotes the formation of covalent bonds (-Si-CH2-C-) between benzophenone and the active groups (-OH, -C=C-) in the hydrogel network and the silica gel polymer chains. This molecular-level covalent anchoring makes the bonding strength between the hydrogel and the substrate and encapsulation layer far exceed that of physical adsorption, effectively solving the problem of electrode detachment.

[0038] In one embodiment of this application, after the impregnation treatment, the swelling degree of the medical-grade silicone at the preset electrode site is preferably 5% to 10%, including but not limited to any one of 5%, 6%, 7%, 8%, 9%, 10%, or any range between two.

[0039] In one embodiment of this application, after the impregnation treatment, the swelling degree of the food-grade silicone adhesive at the preset electrode site is preferably 5% to 10%, including but not limited to any one of 5%, 6%, 7%, 8%, 9%, 10%, or any range between two.

[0040] By precisely controlling the swelling degree of medical-grade silicone and / or food-grade silicone adhesive at preset electrode sites, the silicone polymer on the surface of the medical-grade silicone and / or food-grade silicone adhesive can achieve a better structural state, which is beneficial for further optimizing the covalent cross-linking structure and improving the reliability and conductivity stability of flexible electrode devices.

[0041] It should be noted that this application does not limit the soaking time, as long as the swelling degree is reached; after the swelling degree is reached, excess solution can be removed with absorbent paper, and the solution can be dried with nitrogen or air-dried at room temperature.

[0042] In one embodiment of this application, the molar ratio of benzophenone to the silane coupling agent is 1:10 to 10:1, including but not limited to any one of 1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1 or any range between the two.

[0043] In one embodiment of this application, the mass fraction of benzophenone in the pretreatment solution is preferably 5% to 15%, including but not limited to any one of 5%, 8%, 10%, 12%, and 15%, or any range between two of them.

[0044] By adjusting the amount of benzophenone and silane coupling agent in the pretreatment solution, it is beneficial to further optimize the permeation effect of benzophenone molecules while ensuring the stability of the pretreatment solution.

[0045] In one embodiment of this application, the silane coupling agent includes, but is not limited to, one of aminosilane coupling agents, acryloyloxysilane coupling agents, methacryloxysilane coupling agents, and mercaptosilane coupling agents.

[0046] In one embodiment of this application, the molding process preferably includes thermoforming, which is more conducive to obtaining a flexible silicone substrate that conforms to the contours of the scalp or the back of an animal. It should be noted that this application does not limit the thickness of the flexible substrate, which can be adjusted according to different product requirements. Furthermore, the flexible substrate provided in this application can adopt an ergonomic curved surface design, which is beneficial for fully conforming to areas with dense hair follicles such as the forehead, crown, and temples of the scalp.

[0047] This application also selects liquid metal as the conductive component, which, in conjunction with a flexible substrate of a specific material, an encapsulation layer, and pretreatment steps, has the following technical advantages:

[0048] (1) Liquid metal is liquid at room temperature and has low surface tension. When it comes into contact with medical silicone substrate, it can be fully wetted. After screen printing, it can flow and deform with the bending and stretching of the substrate to form a "flexible substrate-flexible circuit" synergistic system. Compared with traditional rigid conductive silver paste, liquid metal does not require heating and curing and can be formed at room temperature. Moreover, it will not generate internal stress due to substrate deformation, which can effectively avoid problems such as circuit cracking and breakage. At the same time, there is no chemical reaction between liquid metal and silicone substrate. It achieves bonding through physical wetting and mechanical interlocking. The bonding strength is high. It still maintains the integrity of conductive path after repeated deformation (bending 1000 times), which solves the fatigue resistance problem of traditional rigid circuits.

[0049] (2) During the pretreatment of the silicone substrate, some toluene molecules will penetrate to the interface between the liquid metal and the substrate. While the silicone surface is slightly swollen, benzophenone molecules will also be adsorbed on the surface of the liquid metal. The oxide layer on the surface of the liquid metal forms a weak interaction with benzophenone. Under ultraviolet light irradiation, benzophenone is excited to generate free radicals, which not only form covalent bonds with the silicone substrate and hydrogel, but also react with the hydroxyl groups of the oxide layer on the surface of the liquid metal to form a covalent cross-linked network of "liquid metal-benzophenone-hydrogel". This network can effectively eliminate the interfacial gap between the liquid metal and the hydrogel, thereby significantly reducing the contact resistance. At the same time, the covalent cross-linked network can also inhibit the ion migration at the interface between the metal and the hydrogel and block the intrusion of environmental media such as sweat and scalp oil. This ensures that the resistance change rate of the electrode is <10% during long-term use (such as 7 days of continuous wear), which significantly improves the electrical stability and service life.

[0050] (3) Liquid metal has a higher electrical conductivity than traditional stretchable conductive silver paste and conductive polymer, enabling low-loss transmission of electrical stimulation signals. At the same time, the liquid properties of liquid metal ensure that the conductive path remains continuous during substrate deformation, avoiding the resistance abrupt changes caused by deformation in traditional conductive materials, which helps to ensure the stability and accuracy of electrical stimulation signals.

[0051] In one embodiment of this application, the surface tension of the liquid metal is preferably 0.5 N / m to 0.7 N / m, including but not limited to any one of 0.5 N / m, 0.55 N / m, 0.6 N / m, 0.65 N / m, 0.7 N / m or any range between two of them.

[0052] In one embodiment of this application, the electrical conductivity of the liquid metal is preferably 3 × 10⁻⁶. 4 S / cm ~4×10 4 S / cm, including but not limited to 3×10 4 S / cm, 3.2×10 4 S / cm, 3.5×10 4 S / cm, 3.8×10 4S / cm, 4×10 4 Any point value in S / cm or any range of values ​​between the two.

[0053] In one embodiment of this application, the bonding strength between the liquid metal and medical-grade silicone is preferably 0.8 N / cm to 1.2 N / cm, including but not limited to any one of 0.8 N / cm, 0.9 N / cm, 1.0 N / cm, 1.1 N / cm, 1.2 N / cm or any range between two of them.

[0054] In one embodiment of this application, the liquid metal preferably includes at least one of gallium indium alloy, gallium indium tin alloy, gallium indium tin silver alloy, gallium indium tin bismuth alloy, and gallium indium tin zinc alloy.

[0055] Screen printing can be used to create precise patterns such as serpentine lines with a width as low as 1 mm, which can be adapted to the distribution of stimulation target points such as hair follicles.

[0056] In one embodiment of this application, the hydrogel prepolymer includes hydrogel monomers, conductive materials, crosslinking agents, photoinitiators, and solvents. Specifically, the hydrogel monomers include, but are not limited to, hydroxyethyl acrylate (HEA), acrylamide (AM), N-isopropylacrylamide (NIPAM), or acrylic acid (AA). The conductive materials include, but are not limited to, PEDOT:PSS, sodium alginate / calcium chloride systems, and chitosan / glycerol systems, which are beneficial for ensuring the ionic conductivity, biocompatibility, and covalent bonding ability with the substrate of the hydrogel. The photoinitiators include, but are not limited to, LAP, Irgacure 2959 (I2959), and benzoin ether (BE), which are well adapted to short-wave ultraviolet light excitation and have good solubility in the hydrogel system without affecting biocompatibility. The crosslinking agents include, but are not limited to, MBA, and the solvents include, but are not limited to, deionized water.

[0057] In one embodiment of this application, the wavelength for photocuring is preferably 360nm~370nm, including but not limited to any value among 360nm, 362nm, 365nm, 368nm, and 370nm, or any range between two; the intensity is preferably 20mW / cm². 2 ~30mW / cm 2 including but not limited to 20mW / cm 2 23mW / cm 2 25mW / cm 2 27mW / cm 2 30mW / cm 2 The value is any point in the time range or any range between two values; the time is preferably 90s to 120s, including but not limited to any point in the time range of 90s, 100s, 110s, and 120s or any range between two values.

[0058] In one embodiment of this application, the photocuring process further includes dialysis to remove unreacted monomers and impurities, thereby improving biocompatibility. It is understood that this application does not limit the specific operation of the dialysis process; conventional techniques can be used, such as immersing the photocured product in phosphate-buffered saline (PBS) for thorough dialysis.

[0059] In summary, the fabrication method of the flexible electrode device provided in this application has several advantages over traditional technologies:

[0060] (1) The double inert interface between the medical-grade silicone substrate and the food-grade silicone adhesive encapsulation layer is activated by benzophenone pretreatment, and then covalent bond anchoring is formed by UV light induction. The bonding strength between the hydrogel electrode and the substrate is far greater than that of physical adsorption. It can withstand scalp movement, animal scratching and dynamic friction, and solves the problems of displacement and detachment caused by physical adsorption or adhesive of traditional electrodes. It has super strong interface bonding stability, and the covalent bond structure is not affected by water, sweat and scalp oil. There is no risk of open circuit, which meets the stable use requirements of long-term wear or animal experiments. It solves the problem of electrode failure in humid environment and has excellent environmental reliability.

[0061] (2) The ends of the patterned circuit are embedded in situ by hydrogel electrodes, forming a large-area, tightly fused interface. The contact impedance is much lower than that of traditional mechanical connections, and the impedance fluctuation range is small, ensuring low transmission loss and low distortion of the electrical stimulation signal, thus giving the flexible electrode device low and stable contact impedance. At the same time, the stretchable liquid metal circuit deforms in synergy with the flexible substrate and hydrogel, eliminating the risk of cracking or breakage. This solves the signal interruption problem of traditional rigid circuits under deformation and effectively suppresses ion migration at the metal-gel interface, ensuring long-term stability of conductivity and giving the flexible electrode device circuit performance resistant to mechanical fatigue.

[0062] (3) The medical-grade silicone base adheres to the scalp and the curved surface of the animal's head, with uniform pressure distribution; the food-grade silicone adhesive encapsulation layer releases no toxic or harmful substances, and there is no risk of irritation or allergies from long-term skin contact, solving the problem of poor biocompatibility of traditional elastic materials, making the flexible electrode device comfortable to fit and biosafety guaranteed. Furthermore, by using a template to fix the hydrogel electrode at specific points, the target position can be customized according to the distribution of hair follicles or experimental needs, ensuring that the stimulation is accurately applied to the target area and avoiding stimulation deviation caused by displacement. This integrated design can achieve multi-channel synchronous stimulation, breaking through the functional limitations of traditional independent patches, and is suitable for human scalp hair growth and animal experiments (such as promoting hair growth on the back of mice), without the need for additional fixing tools, making operation convenient.

[0063] (4) The food-grade silicone adhesive has good compatibility with the medical-grade silicone substrate material and is firmly bonded. It can effectively wrap the circuit, prevent oxidation and short circuit, and isolate the circuit from the skin, thus improving the safety of use. The encapsulation layer is firm and reliable, which can avoid equipment failure caused by the encapsulation layer falling off. At the same time, the four-layer integrated architecture of "substrate-circuit-encapsulation-electrode" has excellent mechanical matching and can be flexibly deformed with the head or animal body without failure. It takes into account both wearing comfort and structural durability, extends the product's service life, and reduces the cost of use.

[0064] This application provides a flexible electrode device prepared by the method described above, comprising a flexible substrate and an encapsulation layer stacked together; a conductive network is provided between the flexible substrate and the encapsulation layer; the encapsulation layer is provided with a through-hole structure, and a hydrogel electrode passes through the through-hole structure and communicates with the conductive network.

[0065] This application also provides a bioelectric stimulation device, including the flexible electrode device described above.

[0066] The flexible electrode device provided in this application has excellent conductivity stability and high reliability. Bioelectric stimulation devices with this flexible electrode device can be applied to technical fields such as nerve electrical stimulation and tumor immunomodulation adjuvant therapy.

[0067] The flexible electrode device, its fabrication method, and its application will be further described below through specific embodiments. However, those skilled in the art will understand that the following embodiments are for illustrative purposes only and should not be considered as limiting the scope of this application. Unless otherwise specified, specific conditions in the embodiments are performed under conventional conditions or conditions recommended by the manufacturer. Reagents or instruments used without specified manufacturers are all commercially available conventional products.

[0068] Example 1

[0069] Using a hot melt molding process, medical-grade silicone is prepared into a flexible substrate (approximately 1 mm thick) that conforms to the contour of an animal's back, with reserved electrode mounting sites.

[0070] Cover the substrate with a 200-mesh polyester screen, align it with the marked areas, and use a scraper to apply liquid gallium indium tin alloy (surface tension 0.5 N / m, conductivity 4 × 10⁻⁶). 4 The bonding strength with medical-grade silicone is 1.2 N / cm (S / cm). After the screen is scraped and removed, it cures to form a conductive network.

[0071] The flexible printed circuit board (FPCB) interface is connected to the conductive network, and the encapsulated circuit is coated with food-grade silicone adhesive while retaining the preset electrode sites.

[0072] In the pre-defined electrode site area, a toluene solution of benzophenone and aminosilane coupling agent (molar ratio of benzophenone to aminosilane coupling agent is 8:1, total concentration is 10wt%) is used to soak the area for 20 seconds (swelling degree reaches about 8%). Excess solution is absorbed with absorbent paper and dried with nitrogen. A hydrogel prepolymer solution is prepared by adding 20wt% hydroxyethyl acrylate, 10wt% PEDOT:PSS, 0.05wt% MBA, 0.3wt% LAP, and the balance deionized water. The hydrogel prepolymer solution is dropped onto the electrode site and exposed to 365nm ultraviolet light (intensity of 25mW / cm²). 2 Irradiate for 100 seconds to solidify the prepolymer and form a covalent anchor with the substrate. Finally, immerse the prepared flexible electrode device in PBS solution for dialysis for 24 hours.

[0073] Example 2

[0074] Using a hot melt molding process, medical-grade silicone is prepared into a flexible substrate (approximately 1 mm thick) that conforms to the contour of an animal's back, with reserved electrode mounting sites.

[0075] Cover the substrate with a 200-mesh polyester screen, align it with the marked areas, and use a scraper to apply liquid gallium indium alloy (surface tension 0.7 N / m, conductivity 3 × 10⁻⁶). 4 The bonding strength with medical-grade silicone is 1.0 N / cm (S / cm). After the screen is scraped and removed, it cures to form a conductive network.

[0076] The flexible printed circuit board (FPCB) interface is connected to the conductive network, and the encapsulated circuit is coated with food-grade silicone adhesive while retaining the preset electrode sites.

[0077] In the pre-defined electrode site area, a 5 wt% toluene solution of benzophenone and aminosilane coupling agent (molar ratio of benzophenone to aminosilane coupling agent is 5:1, total concentration is 12 wt%) is used to soak the area for 30 seconds (swelling degree reaches about 10%). Excess solution is absorbed with absorbent paper and dried with nitrogen. A hydrogel prepolymer solution is prepared by adding 20 wt% hydroxyethyl acrylate, 10 wt% PEDOT:PSS, 0.05 wt% MBA, 0.3 wt% LAP, and the balance deionized water. The hydrogel prepolymer solution is dropped onto the electrode site and exposed to 370 nm ultraviolet light (intensity of 20 mW / cm²). 2 Irradiate for 90 seconds to solidify the prepolymer and form a covalent anchor with the substrate. Finally, immerse the prepared flexible electrode device in PBS solution for dialysis for 24 hours.

[0078] Example 3

[0079] Using a hot melt molding process, medical-grade silicone is prepared into a flexible substrate (approximately 1 mm thick) that conforms to the contour of an animal's back, with reserved electrode mounting sites.

[0080] Cover the substrate with a 200-mesh polyester screen, align it with the marked areas, and use a scraper to apply liquid gallium indium tin alloy (surface tension 0.5 N / m, conductivity 4 × 10⁻⁶). 4 The bonding strength with medical-grade silicone is 1.2 N / cm (S / cm). After the screen is scraped and removed, it cures to form a conductive network.

[0081] The flexible printed circuit board (FPCB) interface is connected to the conductive network, and the encapsulated circuit is coated with food-grade silicone adhesive while retaining the preset electrode sites.

[0082] In the pre-defined electrode site area, a 15 wt% toluene solution of benzophenone and aminosilane coupling agent (molar ratio of benzophenone to aminosilane coupling agent is 1:1, total concentration is 15 wt%) is used to soak the area for 10 seconds (swelling degree reaches about 5%). Excess solution is absorbed with absorbent paper and dried with nitrogen. A hydrogel prepolymer solution is prepared by adding 20 wt% hydroxyethyl acrylate, 10 wt% PEDOT:PSS, 0.05 wt% MBA, 0.3 wt% LAP, and the remainder deionized water. The hydrogel prepolymer solution is dropped onto the electrode site and exposed to 360 nm ultraviolet light (intensity of 30 mW / cm²). 2 Irradiate for 120 seconds to solidify the prepolymer and form a covalent anchor with the substrate. Finally, immerse the prepared flexible electrode device in PBS solution for dialysis for 24 hours.

[0083] Example 4

[0084] The difference between Example 4 and Example 1 is that the degree of wetting is adjusted so that the degree of swelling reaches about 3%.

[0085] Example 5

[0086] The difference between Example 5 and Example 1 is that the degree of wetting is adjusted so that the degree of swelling reaches about 12%.

[0087] Comparative Example 1

[0088] The difference between Comparative Example 1 and Example 1 is that a silicone substrate and a sheet-like hydrogel electrode were prepared independently, and in use, they were attached to the electrode sites encapsulated with food-grade silicone adhesive using medical conductive adhesive.

[0089] Comparative Example 2

[0090] The difference between Comparative Example 2 and Example 1 is that the pretreatment liquid was not used to wet the preset electrode sites, but the hydrogel prepolymer was directly placed on the preset electrode sites and photocured to form electrodes.

[0091] Comparative Example 3

[0092] The difference between Comparative Example 3 and Example 1 is that the gallium indium tin alloy is replaced with epoxy resin-based conductive silver paste.

[0093] Comparative Example 4

[0094] The difference between Comparative Example 4 and Example 1 is that the gallium indium tin alloy was replaced with PEDOT:PSS-based ink.

[0095] Comparative Example 5

[0096] The difference between Comparative Example 5 and Example 1 is that the gallium indium tin alloy is replaced with graphene conductive paste.

[0097] Comparative Example 6

[0098] The difference between Comparative Example 6 and Example 1 is that medical-grade silicone was replaced with thermoplastic elastomer (TPE).

[0099] Comparative Example 7

[0100] The difference between Comparative Example 7 and Example 1 is that medical-grade silicone was replaced with medical-grade polyurethane (PU).

[0101] Comparative Example 8

[0102] The difference between Comparative Example 8 and Example 1 is that the food-grade silicone adhesive was replaced with medical-grade silicone adhesive.

[0103] Comparative Example 9

[0104] The difference between Comparative Example 9 and Example 1 is that the food-grade silicone adhesive was replaced with a flexible acrylic film.

[0105] Comparative Example 10

[0106] The difference between Comparative Example 10 and Example 1 is that the toluene solvent in the pretreatment solution was replaced with ethanol.

[0107] Comparative Example 11

[0108] The difference between Comparative Example 11 and Example 1 is that the toluene solvent in the pretreatment solution was replaced with acetone.

[0109] Comparative Example 12

[0110] The difference between Comparative Example 12 and Example 1 is that benzophenone in the pretreatment solution was replaced with benzoylbenzoate.

[0111] The flexible electrode devices prepared in all embodiments and comparative examples were subjected to the following performance tests:

[0112] (1) The cross-cut test is a classic engineering test method for evaluating the adhesion (interfacial bonding strength) between a coating, film or composite layer and a substrate. The core principle is to simulate mechanical friction or deformation in actual use by making regular grid-like cuts on the sample surface, and observe whether the coating / composite layer peels off or falls off, thereby quantifying the degree of interfacial bonding.

[0113] (2) Environmental stability impedance test: One end is connected to the gel electrode, and the other end is connected to the rear interface of the electrode cap to test the impedance fluctuation range of the embodiment.

[0114] The test results are shown in Table 1.

[0115] Table 1

[0116]

[0117] As shown in Table 1, compared with the comparative examples, the flexible electrode devices prepared in Examples 1 to 5 exhibit adhesion performance as high as 15.0 MPa and impedance performance of approximately 5 kΩ. The adhesion performance of Examples 4 and 5 is slightly lower than that of Example 1, indicating that adhesion performance can be further optimized by precisely controlling the swelling degree of medical-grade silicone at the preset electrode sites to 5%–10%.

[0118] Comparative Example 1 used a conventional physical bonding process. After 50 cycles of dynamic friction, the electrode displacement rate exceeded 30%, and some electrodes fell off. The adhesive caused mild skin allergies in 20% of the experimental animals, and the contact impedance fluctuation range was 3 times that of Example 1. In Comparative Example 2, since no wetting treatment was performed, the hydrogel was easily peeled off in the cross-cut test.

[0119] Comparative Example 3 used conventional rigid epoxy resin-based conductive silver paste. After repeated bending 100 times, obvious cracks appeared in the circuit, and the resistance change rate exceeded 100%, while the resistance change rate of Example 1 was less than 20%. Comparative Examples 4 and 5 used PEDOT:PSS-based ink and graphene conductive paste instead of liquid metal, respectively. However, both of them require heating to cure, and their impedance performance is not as good as that of Example 1.

[0120] Comparative Examples 6 and 7 used thermoplastic elastomer and medical polyurethane instead of medical-grade silicone as flexible substrates, respectively. Although medical polyurethane has excellent resistance to sweat corrosion, its adhesion performance is not as good as that of Example 1, and toluene will dissolve the medical polyurethane substrate, making it unusable.

[0121] Comparative Examples 8 and 9 used medical-grade silicone sealant and flexible acrylic film instead of food-grade silicone adhesive as the encapsulation layer, respectively. Due to the poor compatibility of medical-grade silicone, the hydrogel was easily peeled off in the cross-cut adhesion test.

[0122] Comparative Examples 10 and 11 used ethanol and acetone as solvents in the pretreatment solution, respectively. The solvent interaction parameters of medical-grade silicone and food-grade silicone adhesives with ethanol were 0.8~1.0, which could not effectively swell the silicone, resulting in a weak subsequent photo-initiated crosslinking effect. Therefore, the adhesion performance of Comparative Example 10 was significantly poor. The solvent interaction parameters of medical-grade silicone and food-grade silicone adhesives with acetone were about 0.6. Due to the limited swelling degree, the subsequent photo-initiated crosslinking effect was weak, resulting in a significantly poor adhesion performance of Comparative Example 11.

[0123] Comparative Example 12 used different photosensitizers. Due to the electron-withdrawing effect of the ester group (-COO-), the free radical activity of the carbonyl group was weakened, and its ability to abstract hydrogen atoms was significantly lower than that of benzophenone. Therefore, it could only weakly initiate the polymerization of hydrogel monomers and was difficult to form stable covalent crosslinks with the silicone surface, resulting in significantly poor adhesion performance.

[0124] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0125] The embodiments described above are merely illustrative of several implementation methods of this application, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the patent. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of this application, and these all fall within the protection scope of this application. Therefore, the protection scope of this patent application should be determined by the appended claims.

Claims

1. A method for fabricating a flexible electrode device, characterized in that, Includes the following steps: Medical-grade silicone is molded to form a flexible substrate; Using liquid metal as raw material, a conductive network is formed by screen printing and curing on the surface of a flexible substrate. After connecting the conductive network to the circuit, it is encapsulated with food-grade silicone adhesive and the preset electrode sites are retained. The preset electrode sites are wetted with a pretreatment solution, and then the hydrogel prepolymer is placed on the preset electrode sites and photocured to form electrodes. The pretreatment solution is a mixed solution of benzophenone and silane coupling agent, and the solvent in the pretreatment solution is toluene. The solvent interaction parameter between medical grade silicone and toluene in the pretreatment solution is 0.4~0.5, and the solvent interaction parameter between food grade silicone adhesive and toluene in the pretreatment solution is 0.4~0.

5.

2. The method for fabricating the flexible electrode device according to claim 1, characterized in that, The surface tension of liquid metal is 0.5 N / m to 0.7 N / m; and / or the electrical conductivity of the liquid metal is 3 x 10 4 S / cm ~ 4 x 10 4 S / cm; And / or, the bonding strength between liquid metal and medical-grade silicone is 0.8 N / cm to 1.2 N / cm; And / or, the liquid metal is selected from at least one of gallium indium alloy, gallium indium tin alloy, gallium indium tin silver alloy, gallium indium tin bismuth alloy, and gallium indium tin zinc alloy.

3. The method for fabricating the flexible electrode device according to claim 1, characterized in that, After impregnation treatment, the swelling degree of medical-grade silicone at the preset electrode sites is 5%~10%.

4. The method for fabricating the flexible electrode device according to claim 1, characterized in that, The molar ratio of benzophenone to the silane coupling agent is 1:10 to 10:1; And / or, the total concentration of benzophenone and silane coupling agent in the pretreatment solution is 1wt%~20wt%; And / or, the silane coupling agent is selected from one of aminosilane coupling agents, acryloyloxysilane coupling agents, methacryloxysilane coupling agents, and mercaptosilane coupling agents.

5. The method for fabricating the flexible electrode device according to claim 1, characterized in that, The forming process includes hot melt forming.

6. The method for fabricating the flexible electrode device according to claim 1, characterized in that, The hydrogel prepolymer solution includes hydrogel monomers, conductive materials, crosslinking agents, photoinitiators, and solvents.

7. The method for fabricating the flexible electrode device according to claim 1, characterized in that, The photocuring wavelength is 360nm~370nm, and the intensity is 20mW / cm². 2 ~30mW / cm 2 The duration is 90s~120s.

8. The method for fabricating the flexible electrode device according to claim 1, characterized in that, After photocuring, dialysis is also required.

9. A flexible electrode device prepared by the method of any one of claims 1 to 8, characterized in that, The flexible electrode device includes a flexible substrate and an encapsulation layer stacked together; a conductive network is provided between the flexible substrate and the encapsulation layer; the encapsulation layer has a through-hole structure, and the hydrogel electrode passes through the through-hole structure and communicates with the conductive network.

10. A bioelectric stimulation device, characterized in that, Including the flexible electrode device as described in claim 9.

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