A self-curling flexible peripheral nerve electrode and methods of making and using the same

Abstract

The application provides a self-coiled flexible peripheral nerve electrode and a preparation method and application thereof, and the preparation method comprises the following steps: preparing a double-layer flexible liquid metal electrode with an exposed site; stretching the double-layer flexible liquid metal electrode, and then fixing two ends of the double-layer flexible liquid metal electrode to obtain a stretched electrode; coating a polymer prepolymer reaction solution on a surface of the stretched electrode which is opposite to the exposed site, and curing the polymer prepolymer reaction solution to form a fixing layer, so as to obtain a three-layer composite electrode; under the condition that the two ends are fixed, the fixing layer in the three-layer composite electrode faces downward, the fixing of one end of the three-layer composite electrode is released, and the three-layer composite electrode is self-coiled. The self-coiled flexible peripheral nerve electrode prepared by the preparation method of the self-coiled flexible peripheral nerve electrode has high conductivity, can realize self-coiling of the electrode, improves the detection quality and long-term stability of nerve signals, and avoids mechanical damage of nerve tissue caused by electrode implantation.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of flexible neural electrode, in particular to a self-curling flexible peripheral nerve electrode and a preparation method and application thereof. BACKGROUND

[0002] Peripheral nerve signal acquisition and electrical stimulation treatment has wide clinical application value in the diagnosis of special diseases such as depression, epilepsy and prosthesis which are difficult to treat by traditional drugs. Peripheral nerve electrode is the core component connecting external acquisition device and peripheral nerve tissue, which plays a decisive role in nerve signal acquisition quality and electrical stimulation treatment effect. The commonly used peripheral nerve electrode, such as Cuff electrode, mainly adopts the method of wrapping and winding the outer layer of peripheral nerve with insulating sleeve to collect signal and stimulate the peripheral nerve. However, the Young's modulus of the peripheral nerve electrode in the prior art is quite different from the soft nerve bundle, which is easy to cause mechanical damage to the nerve bundle after implantation, and the lock type sleeve cannot completely conform to the nerve bundle. If it is wrapped too loosely, it will affect the quality of nerve signal acquisition, and if it is wrapped too tightly, it will cause serious compression to the nerve bundle and affect the normal nerve conduction function. In addition, the Cuff peripheral nerve electrode mainly uses polymer material as the electrode base material, combined with additional lock structure to wrap or wrap the nerve bundle. It lacks a safe and efficient electrode matching method for high-precision and high-throughput implantable nerve signal acquisition. It is urgent to develop a flexible peripheral nerve electrode with self-curling performance and low elastic modulus, which has important clinical value to meet the long-term implantation needs of peripheral nerve. SUMMARY

[0003] The problem solved by the present application is to provide a self-curling flexible peripheral nerve electrode with high conductivity, which can realize self-curling wrapping of the electrode, improve the detection quality and long-term stability of the nerve signal, and avoid mechanical damage to the nerve tissue caused by electrode implantation.

[0004] To solve at least one aspect of the above problem, the present application provides a preparation method of a self-curling flexible peripheral nerve electrode, comprising the following steps:

[0005] Step S1, preparing a double-layer flexible liquid metal electrode with an exposed site;

[0006] Step S2, stretching the double-layer flexible liquid metal electrode, and then fixing the two ends of the double-layer flexible liquid metal electrode to obtain a stretched electrode;

[0007] Step S3, coating a high molecular pre-polymer reaction solution on the surface of the stretched electrode opposite to the exposed site, and forming a fixed layer after solidifying the high molecular pre-polymer reaction solution to obtain a three-layer composite electrode;

[0008] Step S4, the fixed layer in the three-layer composite electrode is made to face downward while keeping both ends fixed, the fixation of one end of the three-layer composite electrode is released, the three-layer composite electrode is self-coiled, and a self-coiled flexible peripheral nerve electrode is obtained.

[0009] Preferably, the step S1 comprises: combining a liquid metal electrode with a flexible substrate to obtain an electrode layer, and then encapsulating the electrode layer using a flexible polymer to obtain the double-layer flexible liquid metal electrode with the electrode layer and the encapsulation layer.

[0010] Preferably, the preparation method of the electrode layer comprises one of a screen printing method, an inkjet printing method and a micro-channel pipe filling method.

[0011] Preferably, the first flexible substrate comprises one or more of thermoplastic polyurethane, polycaprolactone, polylactic acid-glycolic acid copolymer, polyurethane, polystyrene-polybutadiene-polystyrene copolymer, polydimethylsiloxane and copolyester.

[0012] Preferably, in the step S2, the double-layer flexible liquid metal electrode comprises a pre-coiled area and a non-pre-coiled area, and only the pre-coiled area is stretched in the stretching process.

[0013] Preferably, in the step S2, the stretching rate of the double-layer flexible liquid metal electrode is 50-700%.

[0014] Preferably, in the step S3, the high-molecular pre-polymer reaction solution comprises a high-molecular pre-polymer and a curing agent, wherein the high-molecular pre-polymer comprises polydimethylsiloxane.

[0015] The present application changes the stress of the double-layer flexible liquid metal electrode by stretching the double-layer flexible liquid metal electrode with exposed sites, then coats a layer of high-molecular pre-polymer on the stretched electrode and cures it. Since the stress of the stretched electrode and the cured high-molecular pre-polymer is different, the electrode is self-coiled by internal stress driving when the fixation of one end is released. Compared with manual coiling or coiling with O-ring fixation, the influence of human factors is reduced, the electrode can better fit the nerve tissue, the detection quality and sensitivity of nerve signals are improved, the wrapping effect on nerve bundles is better, and the long-term stability is good. The liquid metal electrode has good tensile properties and high conductivity, the exposed sites in the double-layer flexible liquid metal electrode can be connected with wires, and the electrode used as a nerve signal acquisition electrode has good detection sensitivity and stability. The self-coiled flexible peripheral nerve electrode prepared by the preparation method of the self-coiled flexible peripheral nerve electrode provided by the present application has high conductivity, can realize self-coiling of the electrode, improve the detection quality and long-term stability of nerve signals, and avoid mechanical damage to nerve tissue caused by electrode implantation.

[0016] Another object of the present application is to provide a self-curling flexible peripheral nerve electrode prepared by the preparation method of the self-curling flexible peripheral nerve electrode as described above.

[0017] Preferably, the self-curling flexible peripheral nerve electrode comprises an encapsulation layer, an electrode layer and a fixing layer; wherein the electrode layer comprises a flexible substrate and a liquid metal electrode embedded on the flexible substrate; the encapsulation layer covers the surface of the liquid metal electrode; and the fixing layer is located below the electrode layer.

[0018] The self-curling flexible peripheral nerve electrode provided by the present application has the same beneficial effects as the preparation method of the self-curling flexible peripheral nerve electrode compared with the prior art, which will not be described here again.

[0019] Another object of the present application is to provide the use of the self-curling flexible peripheral nerve electrode as described above in peripheral nerve signal acquisition and electrical stimulation treatment.

[0020] The use of the self-curling flexible peripheral nerve electrode provided by the present application has the same beneficial effects as the preparation method of the self-curling flexible peripheral nerve electrode compared with the prior art, which will not be described here again. BRIEF DESCRIPTION OF DRAWINGS

[0021] Figure 1 The flow chart of the preparation method of the self-curling flexible peripheral nerve electrode in the embodiments of the present application;

[0022] Figure 2 The structural schematic diagram of the self-curling flexible peripheral nerve electrode in the embodiments of the present application;

[0023] Figure 3 The self-curling process schematic diagram of the self-curling flexible peripheral nerve electrode in Embodiment 1 of the present application;

[0024] Figure 4 The side view of the self-curling peripheral nerve electrode in Embodiment 1 of the present application;

[0025] Figure 5 The scanning electron microscope image of the self-curling peripheral nerve electrode in Embodiment 1 of the present application;

[0026] Figure 6 The relationship diagram between the elongation rate of the self-curling peripheral nerve electrode in Embodiment 1 of the present application and the innermost circle diameter of the curled part thereof.

[0027] EXPLANATION OF REFERENCE NUMERALS:

[0028] 1, encapsulation layer; 2, electrode layer; 3, fixing layer. DETAILED DESCRIPTION

[0029] In order to make the above objectives, characteristics and advantages of the present application more apparent and comprehensible, specific embodiments of the present application are described in detail below.

[0030] It should be noted that the features in the embodiments of the present application can be combined with each other without conflict. The terms "comprise", "include", "contain", "have" are non-limiting, i.e. other steps and other components can be added without affecting the results. The above terms encompass the terms "consist of" and "consist essentially of". Unless otherwise specified, the materials, devices, reagents are commercially available.

[0031] The embodiment of the present application provides a preparation method of a self-coiled flexible peripheral nerve electrode, as shown in the figure, comprising the following steps: Figure 1 As shown in the figure, comprising the following steps:

[0032] Step S1, preparing a double-layer flexible liquid metal electrode with an exposed site;

[0033] Step S2, stretching the double-layer flexible liquid metal electrode, and then fixing both ends of the double-layer flexible liquid metal electrode to obtain a stretched electrode;

[0034] Step S3, coating a polymer prepolymer reaction solution on the side of the stretched electrode opposite to the exposed site, and forming a fixed layer 3 after curing the polymer prepolymer reaction solution to obtain a three-layer composite electrode;

[0035] Step S4, keeping the fixed layer 3 of the three-layer composite electrode facing down while keeping both ends fixed, and releasing the fixation of one end of the three-layer composite electrode, and the three-layer composite electrode is self-coiled to obtain a self-coiled flexible peripheral nerve electrode.

[0036] In step S1, the liquid metal electrode is combined with the flexible substrate to obtain an electrode layer 2, and then the electrode layer 2 is packaged with a flexible polymer to obtain the double-layer flexible liquid metal electrode with the electrode layer 2 and the packaging layer 1.

[0037] Specifically, the liquid metal electrode is combined with the flexible substrate to obtain the electrode layer 2 by a screen printing method, an inkjet printing method or a micro-channel pipeline filling method; wherein the material of the flexible substrate includes one or more of thermoplastic polyurethane (TPU), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA), polyurethane (PU), polystyrene-polybutadiene-polystyrene copolymer (SBS), polydimethylsiloxane (PDMS) and copolyester (Ecoflex).

[0038] Exemplarily, when the screen printing method is selected to prepare the electrode layer 2, the following steps are included: (1) adding liquid metal into a solvent, mixing uniformly to obtain liquid metal ink; (2) designing an electrode array pattern, and preparing a screen printing mask plate according to the electrode array pattern; (3) printing the liquid metal ink onto a PET substrate through the screen printing mask plate; (4) coating a flexible substrate material solution on the PET substrate, drying and curing to form a flexible substrate, and taking the flexible substrate away from the PET substrate, that is, transferring the liquid metal electrode on the PET substrate to the flexible substrate, to obtain the electrode layer 2.

[0039] After obtaining the electrode layer 2, the flexible polymer is used to encapsulate by the hot pressing method or the spin coating method, wherein the flexible polymer includes one or more of TPU, PCL, PLGA, PU, SBS, PDMS and Ecoflex.

[0040] The flexible substrate and the flexible polymer have good biocompatibility, mechanical properties and good ductility.

[0041] It should be understood that when the flexible polymer is selected, it should be considered whether the flexible polymer can be well attached to the flexible substrate in the electrode layer 2, that is, according to the selection of the flexible substrate material, a suitable flexible polymer is selected for encapsulation. In addition, when the electrode layer 2 is encapsulated, the exposure of the exposed site needs to be considered. Exemplarily, Ecoflex 00-30 (purchased from Smooth-On Company) is selected to occupy the position of the exposed site on the electrode layer 2, heated and cured, then the flexible polymer solution is coated, heated to a semi-cured state, the cured Ecoflex 00-30 is removed, and then the electrode layer 2 is heated to completely cure the flexible polymer, to obtain a double-layer flexible liquid metal electrode with suitable exposed sites.

[0042] In step S2, the double-layer flexible liquid metal electrode is stretched, and then both ends are fixed to obtain a stretched electrode.

[0043] In some embodiments, the double-layer flexible liquid metal electrode is stretched with the exposed site downward, and then both ends are fixed, to facilitate coating of a polymer prepolymer reaction solution in the subsequent step.

[0044] The stress of the double-layer flexible liquid metal electrode is changed by stretching the double-layer flexible liquid metal electrode and fixing both ends of the double-layer flexible liquid metal electrode, wherein the stretching rate of the double-layer flexible liquid metal electrode is 50-700%, and a too small stretching rate is easy to cause a too small stress difference between the stretched double-layer liquid metal electrode and the fixed layer 3, so that the self-rolling cannot be realized, and a too large stretching rate is easy to cause the separation between the encapsulation layer 1 and the electrode layer 2 during the stretching. Moreover, with the increase of the stretching rate, the stress of the double-layer flexible liquid metal electrode after being stretched increases, the stress difference between the double-layer flexible liquid metal electrode after being stretched and the fixed layer 3 increases, and the innermost diameter of the self-rolling part is smaller.

[0045] It should be understood that the stretching rate range of the double-layer flexible liquid metal electrode is different when the flexible substrate and the flexible polymer used in the double-layer flexible liquid metal electrode are different, for example, when PDMS is selected as the flexible substrate and the flexible polymer, the stretching rate range is 50-430%, and when TPU is selected as the flexible substrate and the flexible polymer, the stretching rate can be up to 700%. In addition, the thickness of the encapsulation layer 1 and the electrode layer 2 also affects the stretching rate range.

[0046] Further, the double-layer flexible liquid metal electrode comprises a pre-rolling area and a non-pre-rolling area, and only the pre-rolling area is stretched during the stretching. By dividing the double-layer flexible liquid metal electrode into the pre-rolling area and the non-pre-rolling area, the self-rolling flexible peripheral nerve electrode obtained finally can be partially rolled, that is, the pre-rolling area can be self-rolled, and the non-pre-rolling area remains normal, so that the application range of the self-rolling flexible peripheral nerve electrode prepared can be further improved.

[0047] In step S3, a polymer prepolymer reaction solution is coated on the surface of the stretched electrode opposite to the exposure site, the polymer prepolymer reaction solution is solidified to form a fixed layer 3, and a three-layer composite electrode is obtained; wherein the polymer prepolymer reaction solution comprises a polymer prepolymer and a curing agent, and the polymer prepolymer comprises polydimethylsiloxane (PDMS). Coating the polymer prepolymer reaction solution on the surface of the stretched electrode opposite to the exposure site can avoid that the fixed layer 3 formed after the solidification of the polymer prepolymer reaction solution covers the exposure site.

[0048] Since the stretched electrode is fixed at both ends after being stretched, the stretched electrode has a large stress, and the fixed layer 3 has a normal stress, so there is a stress difference between the stretched electrode and the fixed layer 3.

[0049] In step S4, the fixed layer 3 of the three-layer composite electrode is made to face downward while keeping both ends fixed, and the fixation of one end is released, so that the three-layer composite electrode is self-rolled to obtain a self-rolled flexible peripheral nerve electrode. In the process of making the fixed layer 3 of the three-layer composite electrode face downward, i.e. the packaging layer 1 is on the top and the fixed layer 3 is on the bottom, while keeping both ends fixed, the fixation of one end is released, so that the three-layer composite electrode is rolled toward the direction with greater stress due to the greater stress of the packaging layer 1 and the electrode layer 2 and the smaller stress of the fixed layer 3, thereby obtaining a self-rolled flexible peripheral nerve electrode.

[0050] Exemplarily, the fixed layer 3 of the three-layer composite electrode is made to face downward, both ends of the three-layer composite electrode are fixed by using adhesive tape, and one end of the three-layer composite electrode is cut by using a blade, i.e. the fixation of one end is released, so that the end of the three-layer composite electrode with the released fixation can be rolled toward the direction with greater stress due to the greater stress of the packaging layer 1 and the electrode layer 2 and the smaller stress of the fixed layer 3.

[0051] Another embodiment of the present application provides a self-rolled flexible peripheral nerve electrode prepared by using the preparation method of the self-rolled flexible peripheral nerve electrode as described above.

[0052] Specifically, as shown in Figure 2 , Figure 2 Fig. (a) is a side view of the self-rolled flexible peripheral nerve electrode, Figure 2 Fig. (b) is a schematic view of the self-rolled flexible peripheral nerve electrode, which comprises a packaging layer 1, an electrode layer 2 and a fixed layer 3; wherein the electrode layer 2 comprises a flexible substrate and a liquid metal electrode embedded on the flexible substrate, the liquid metal electrode comprises a wire and exposed sites at both ends of the wire; the packaging layer 1 covers the surface of the liquid metal electrode; and the fixed layer 3 is located below the electrode layer 2.

[0053] Preferably, the self-rolled flexible peripheral nerve electrode has a pre-rolled region and a non-pre-rolled region, wherein the pre-rolled region is self-rolled by internal stress driving, which reduces the influence of human factors compared with the manual rolling or the rolling using an O-ring in the prior art, and can better fit the nerve tissue, thereby increasing the detection quality and sensitivity.

[0054] Still another embodiment of the present application provides the use of the self-rolled flexible peripheral nerve electrode as described above in peripheral nerve signal acquisition and electrical stimulation treatment.

[0055] Because this self-rolling flexible peripheral nerve electrode has good biocompatibility, high conductivity and excellent tensile properties, and these properties are stable over a long period of time, it can achieve self-rolling and wrapping of the electrode, resulting in good adhesion to the surface of the nerve bundle. This improves the detection quality and long-term stability of nerve signals and avoids mechanical damage to nerve tissue caused by electrode implantation.

[0056] The present invention will be further illustrated below through specific embodiments. However, these embodiments are merely for the purpose of helping to understand the present invention and should not be used to limit the present invention in any way.

[0057] Example 1

[0058] 1.1 Weigh 8g of gallium indium alloy and add it to 1mL of n-decyl alcohol. Use an ultrasonic cell disruptor to sonicate at 28% amplitude for 5min. The liquid metal is transformed into micro-nano particles under ultrasonic action to obtain liquid metal ink.

[0059] 1.2 The electrode array pattern is designed using AutoCAD software. The array pattern contains 8 electrodes. Each electrode includes an electrode site, an interface, and a wire connecting the electrode site and the interface. The diameter of the electrode site is 60μm, the spacing between adjacent electrode sites is 200μm, and the line width of the wire is 20μm. A professional manufacturer prepares a screen printing mask based on the electrode pattern.

[0060] 1.3. Using a screen printing mask, liquid metallic ink is printed onto a polyethylene terephthalate (PET) substrate;

[0061] 1.4. Mix TPU and N,N-dimethylformamide (DMF) at a mass ratio of 12:88 until homogeneous, and then spin-coat the mixture onto the PET substrate from step 1.3 at a spin speed of 2000 rpm for 60 s. Then, place the PET substrate in a forced-air drying oven and bake at 80°C for 15 min. Remove the substrate from the oven and carefully remove the TPU film from the PET substrate. Transfer this liquid metal electrode onto the TPU film to obtain the electrode layer.

[0062] 1.5. Mix PDMS prepolymer and curing agent at a mass ratio of 10:1 to prepare PDMS prepolymer reaction solution; mix components A and B of Ecoflex00-30 (purchased from Smooth-On) at a mass ratio of 1:1 to obtain Ecoflex00-30 reaction solution.

[0063] 1.6, using Ecoflex 00-30 reaction liquid to occupy the exposed site on the electrode layer (i.e. the head and tail end of the electrode), the electrode layer is placed in an oven at 80°C for about 5 min to solidify the Ecoflex 00-30 reaction liquid; after taking out, spin-coating PDMS prepolymer reaction liquid on the liquid metal electrode surface of the electrode layer, the speed is 1000 rpm, and the time is 60 s; then placed in an oven at 80°C for 3 min, at this time the PDMS is in a semi-cured state, after taking out, the cured Ecoflex is removed, the exposed site is exposed, and the exposed site is obtained; then placed in an oven at 80°C for about 30 min to solidify the PDMS prepolymer reaction liquid, after taking out the double-layer flexible liquid metal electrode, a silver wire is placed at the tail end, and the silver paste is used to wrap the electrode tail end with the silver wire, so as to realize good conduction of the silver wire and the electrode, and placed for 15 min to wait for the formation of an oxide layer on the surface of the silver paste, a small amount of mixed and uniform Ecoflex 00-30 reaction liquid is added to the electrode tail end, and placed in an oven at 80°C for about 5 min to solidify the Ecoflex, and a double-layer flexible liquid metal electrode is obtained;

[0064] 1.7, after the double-layer flexible liquid metal electrode is stretched to 200% of the original length (i.e. the stretching rate is 100%) along the pre-curling direction, the exposed site is placed downward in a culture dish and fixed well at the appropriate position by adhesive tape, and a stretched electrode is obtained;

[0065] 1.8, spin-coating PDMS prepolymer reaction liquid on the stretched electrode, the speed is 2000 rpm, and the time is 60 s, then placed in an oven at 80°C for about 30 min to solidify the PDMS prepolymer reaction liquid to form a solidification layer, and a three-layer composite electrode is obtained;

[0066] 1.9, the three-layer composite electrode is taken out with the adhesive tape by a scalpel, placed upside down and fixed at both ends of the pre-curling area, then the three-layer composite electrode is cut open at the curling end along the adhesive tape by using a scalpel, and due to the driving of internal stress, the three-layer composite electrode will curl by itself to form an outer peripheral nerve electrode with a multi-layer curl structure as shown in Figure 3 Figure 4

[0067] wherein, Figure 3 is the curling process of the three-layer composite electrode after cutting open the curling end in this embodiment, Figure 3 (a), (b), (c) and (d) are the curling states at 0 s, 1 s, 2 s and 3 s, respectively; Figure 4 is a side view of the self-curling flexible peripheral nerve electrode prepared in this embodiment.

[0068] The obtained self-curling flexible peripheral nerve electrode is scanned by a scanning electron microscope (SEM), as shown in Figure 5 ​​As shown, the self-curling flexible peripheral nerve electrode pre- curling zone achieves good fit between the layers, and the self-curling part has a small inner diameter.

[0069] Self-curling flexible peripheral nerve electrodes were prepared under different stretching conditions, and the inner diameter of the self-curling part of the self-curling flexible peripheral nerve electrodes obtained under different stretching conditions was measured by SEM, and the relationship between the innermost circle diameter of the self-curling part and the stretching rate was obtained; as shown, Figure 6 As shown, as the stretching rate increases, the innermost circle diameter becomes smaller and smaller, which is mainly due to the fact that the greater the stretching rate, the greater the stress of the electrode after stretching, and the greater the stress difference between the stretched electrode and the fixed layer 3, thereby resulting in a smaller innermost circle diameter of the self-curling part.

[0070] Example 2

[0071] 2.1, 3.5g of indium alloy was weighed into 0.5ml n-decanol, and an ultrasonic cell disruptor was used to ultrasonic at 30% amplitude for 5min, and the liquid metal was converted into micro-nanoparticles under the action of ultrasonic, and a liquid metal ink was obtained;

[0072] 2.2, the electrode array pattern was designed by AutoCAD software, there were 8 electrodes in the array pattern, each electrode included electrode sites, interfaces and wires connecting the electrode sites and interfaces, the diameter of the electrode sites was 60μm, the distance between adjacent electrode sites was 200μm, and the line width of the wire was 20μm, a screen printing mask plate was prepared according to the electrode pattern by a professional manufacturer;

[0073] 2.3, using the screen printing mask plate, the liquid metal ink was printed on the polyethylene terephthalate (PET) substrate;

[0074] 2.4, the TPU and N,N-dimethylformamide (DMF) were mixed in a mass ratio of 22:78 and then spin-coated on the PET substrate in step 2.3, the spin-coating speed was 500rpm and the time was 30s; then the PET substrate was placed in a forced air drying oven at 80℃ for 15min, and then taken out of the oven; the TPU film was carefully removed from the PET substrate, and the liquid metal electrode was transferred to the TPU film to obtain an electrode layer;

[0075] 2.5, the electrode exposure site was designed by CAD, and the PU film was punched by a laser puncher, and the exposure site of the PU film should be slightly larger than the exposure site of the electrode. The PU film with the exposure site was placed on the TPU film, and the exposure site of the head of the PU film was aligned with the electrode head site of the head of the TPU film. A PET sheet was placed below the TPU film and above the PU film, and the electrode was hot-pressed by a hot press at a temperature of 130℃ for 5min to obtain a double-layer flexible liquid metal electrode;

[0076] 2.6, after the double-layer flexible liquid metal electrode is stretched to 600% of the original length along the pre-wrinkling direction (i.e. the stretching rate is 500%), the exposed sites are placed downwards in a culture dish and fixed well in place by adhesive tape, to obtain a stretched electrode;

[0077] 2.7, the PDMs prepolymer reaction solution is spin-coated on the stretched electrode at a speed of 1000 rpm for 30 s, and then placed in an oven at 80°C for about 30 min to solidify the PDMS prepolymer reaction solution to form a solidified layer, to obtain a three-layer composite electrode;

[0078] 2.8, the three-layer composite electrode is taken out with a scalpel together with the adhesive tape, placed upside down and fixed at both ends of the pre-wrinkling area, and then cut open along the adhesive tape at the rolled end using a scalpel, and due to the driving of internal stress, the three-layer composite electrode will self-wrinkle to form a peripheral nerve electrode with a multi-layer roll structure, to obtain a self-wrinkled flexible peripheral nerve electrode.

[0079] Example 3

[0080] 3.1, 6g of gallium-indium alloy is weighed into 1mL of n-decanol, and an ultrasonic cell disruptor is used to ultrasonicate at 30% amplitude for 5min, and the liquid metal is converted into micro-nanoparticles under the action of ultrasonic waves, to obtain a liquid metal ink;

[0081] 3.2, an electrode array pattern is designed by AutoCAD software, and the array pattern includes 8 electrodes in total, each electrode including an electrode site, an interface, and a wire connecting the electrode site and the interface, the diameter of the electrode site is 60μm, the spacing between adjacent electrode sites is 200μm, and the line width of the wire is 20μm, and a screen printing mask plate is prepared according to the electrode pattern by a professional manufacturer;

[0082] 3.3, the screen printing mask plate is used to print the liquid metal ink on the PET substrate;

[0083] 3.4, 4g of PCL particles, 14mL of N,N-dimethylformamide solvent, and 14mL of tetrahydrofuran solvent are stirred uniformly and spin-coated on the PET substrate in step 3.3 at a speed of 1200 rpm for 60 s, and then the PET substrate is placed in a forced air drying oven at 80°C for 30 min, taken out of the oven, and the PCL film is removed from the PET substrate, so that the liquid metal electrode is transferred to the polymer film, to obtain an electrode layer;

[0084] 3.5, PDMS prepolymer and curing agent were mixed in a mass ratio of 10:1 to prepare a PDMS prepolymer reaction solution; A and B components of Ecoflex 00-30 (purchased from Smooth-On Company) were uniformly mixed in a mass ratio of 1:1 to obtain an Ecoflex 00-30 reaction solution;

[0085] 3.6, the Ecoflex 00-30 reaction solution was used to occupy the exposed sites on the electrode layer (i.e. the head and tail ends of the electrode), and the electrode layer was placed in an oven at 80°C for about 5 min to cure the Ecoflex 00-30 reaction solution; after taking out, the PDMS prepolymer reaction solution was spin-coated on the surface of the liquid metal electrode of the electrode layer at a speed of 1000 rpm for 60 s; then it was placed in an oven at 80°C for 3 min, at this time the PDMS was in a semi-cured state, after taking out, the cured Ecoflex was removed, the exposed sites were exposed, and the exposed sites were obtained; then it was placed in an oven at 80°C for about 30 min to cure the PDMS prepolymer reaction solution, and the double-layer flexible liquid metal electrode was taken out, silver wires were placed at the tail end, and silver paste was used to wrap the electrode tail end with the silver wires, so as to realize good conduction between the silver wires and the electrode, and the silver paste was placed for 15 min to form an oxide layer on the surface, a small amount of mixed and uniform Ecoflex 00-30 reaction solution was added to the electrode tail end, and it was placed in an oven at 80°C for about 5 min to cure the Ecoflex, and a double-layer flexible liquid metal electrode was obtained;

[0086] 3.7, after the double-layer flexible liquid metal electrode was stretched to 150% of the original length along the pre-curling direction (i.e. the stretching rate was 50%), the exposed sites were placed downward in a culture dish and fixed at a suitable position by adhesive tape, and a stretched electrode was obtained;

[0087] 3.8, the PDMS prepolymer reaction solution was spin-coated on the stretched electrode at a speed of 2000 rpm for 60 s, and then it was placed in an oven at 80°C for about 30 min to cure the PDMS prepolymer reaction solution to form a cured layer, and a three-layer composite electrode was obtained;

[0088] 3.9, the three-layer composite electrode was taken out with the surgical knife and adhesive tape, placed upside down on a PET sheet, and the two ends were fixed;

[0089] 3.10, take an adult SD rat, pentobarbital with a dose of 50 mg / kg of SD rats anesthetized, using 70% alcohol solution of the mouse skin disinfection, the mouse abdominal skin up, using surgical scissors in the urethral opening near the skin open a small mouth, using surgical scissors from the urethral opening near the cut to the sternum xiphoid skin, using surgical scissors from the urethral opening near the cut to the skin near the knee. Using forceps to open the skin to the outside, using a scalpel in the tail of the bottom of the incision along the spine to peel the gluteal muscle, the two hind limbs of the fixed contact and using a hand holding the two hind legs of the calf position, the other hand tightly holding the rat tail, the tail gently from the hind legs to pull away, when you see the white sciatic nerve can stop, the sciatic nerve around the muscle gently apart to separate the sciatic nerve;

[0090] 3.11, the PET sheet with three layers of composite electrode is placed under the sciatic nerve, the head exposure site close to the sciatic nerve, using a scalpel in the head exposure site close to the electrode to cut open to release the electrode, and slowly to the electrode head moving PET sheet to achieve good electrode to the sciatic nerve package.

[0091] Although the present disclosure is disclosed as above, the protection scope of the present disclosure is not limited to this. Those skilled in the art can make various changes and modifications without departing from the spirit and scope of the present disclosure, and these changes and modifications will fall within the protection scope of the present disclosure.

Claims

1. A method for preparing a self-curling flexible peripheral nerve electrode, characterized in that, Includes the following steps: Step S1: Prepare a bilayer flexible liquid metal electrode with exposed sites; Step S2: Stretch the double-layer flexible liquid metal electrode, and then fix both ends of the double-layer flexible liquid metal electrode to obtain a stretched electrode; the double-layer flexible liquid metal electrode includes a pre-curled area and a non-pre-curled area, and only the pre-curled area is stretched during the stretching process; Step S3: Coat the surface of the stretching electrode opposite to the exposed site with a polymer prepolymer reaction liquid, and solidify the polymer prepolymer reaction liquid to form a fixing layer (3) to obtain a three-layer composite electrode; Step S4: While keeping both ends fixed, make the fixing layer (3) of the three-layer composite electrode face down, release the fixation of one end of the three-layer composite electrode, and the three-layer composite electrode completes self-rolling to obtain a self-rolling flexible peripheral nerve electrode.

2. The method for preparing a self-curling flexible peripheral nerve electrode according to claim 1, characterized in that, Step S1 includes: combining a liquid metal electrode with a flexible substrate to obtain an electrode layer (2), and then encapsulating the electrode layer (2) with a flexible polymer to obtain the double-layer flexible liquid metal electrode having an electrode layer (2) and an encapsulation layer (1).

3. The method for preparing a self-coiling flexible peripheral nerve electrode according to claim 2, characterized in that, The electrode layer (2) is prepared by one of the following methods: screen printing, inkjet printing, and microchannel filling.

4. The method for preparing a self-curling flexible peripheral nerve electrode according to claim 2, characterized in that, The flexible substrate includes one or more of polycaprolactone, polylactic acid-glycolic acid copolymer, polyurethane, polystyrene-polybutadiene-polystyrene copolymer, polydimethylsiloxane, and copolyester.

5. The method for preparing a self-curling flexible peripheral nerve electrode according to claim 1, characterized in that, In step S2, the stretching ratio of the double-layer flexible liquid metal electrode is 50-700%.

6. The method for preparing a self-curling flexible peripheral nerve electrode according to claim 1, characterized in that, In step S3, the polymer prepolymer reaction liquid includes a polymer prepolymer and a curing agent, wherein the polymer prepolymer includes polydimethylsiloxane.

7. A self-curling flexible peripheral nerve electrode, characterized in that, It was prepared using the method described in any one of claims 1-6 for the preparation of a self-curling flexible peripheral nerve electrode.

8. The self-coiling flexible peripheral nerve electrode according to claim 7, characterized in that, It includes an encapsulation layer (1), an electrode layer (2), and a fixing layer (3); The electrode layer (2) includes a flexible substrate and a liquid metal electrode embedded in the flexible substrate; The encapsulation layer (1) covers the surface of the liquid metal electrode; The fixing layer (3) is located below the electrode layer (2).

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