Graphene neural electrode, preparation method therefor, and use thereof

Abstract

A graphene neural electrode, a preparation method therefor, and use thereof. The preparation method comprises the following steps: (1) performing laser printing on a polyimide film according to a preset electrode pattern to obtain laser-induced graphene; (2) subjecting the laser-induced graphene to transfer printing to a water-soluble adhesive tape, then arranging a thermoplastic polymer thin film on one side of the laser-induced graphene away from the water-soluble adhesive tape, and then removing the water-soluble adhesive tape, so that the laser-induced graphene is subjected to transfer printing to the thermoplastic polymer thin film to obtain a first prefabricated product; (3) placing the first prefabricated product in a conductive polymer monomer solution for electrochemical polymerization, and forming a conductive polymer layer to obtain a second prefabricated product; and (4) arranging a thermoplastic polymer packaging layer on the conductive polymer layer of the second prefabricated product to obtain the graphene neural electrode. The graphene neural electrode prepared by using the method has excellent flexible characteristics and mechanical properties, high mechanical and electrochemical stability, and low electrochemical impedance, thereby achieving long-term stable signal monitoring in an organism.

Description

A graphene neural electrode and its preparation method and application Technical Field

[0001] The present application belongs to the field of biomedical materials technology, and specifically relates to a graphene neural electrode and its preparation method and application. Background Art

[0002] As we all know, the brain, a biological tissue composed of nerve cells, is a comprehensive organ responsible for complex functions such as learning, memory, movement, and thinking. Neurons emit neural signals, forming neural circuits. Implantable neural electrodes are one of the key tools for revealing brain neural circuits and treating neurological diseases. They can convert complex neural signals within the brain into recognizable electrical signals, enabling communication between the human brain and machines. Therefore, neural electrodes play a key role in understanding the brain and cracking its code. In addition, neural electrodes are of great significance for the diagnosis and mechanism research of neurological diseases. For example, neural electrodes can be used to stimulate neurons in the cerebral cortex of epilepsy patients, achieving treatment through neuromodulation. For Parkinson's disease patients, neural electrodes can be used to study the neural circuit mechanisms, identify the disease's causes, and develop relevant treatment strategies. For patients with amputations or paralysis, neural signals can be extracted to control tools such as wheelchairs or prosthetic limbs, helping patients live better lives. In short, the development of neural electrode technology is of great significance for human research on the brain and the ability to read and control brain information.

[0003] According to the difference in mechanical properties of neural electrodes, they can be divided into two categories: rigid neural electrodes and flexible neural electrodes. At present, the rigid neural electrodes used in clinical practice mainly include: metal microwire electrodes and silicon-based electrodes. Metal microwire electrodes are usually made of metal materials such as platinum, iridium, tungsten, nickel-chromium alloy, etc. to make microwires with a diameter of less than 100μm, and an insulating layer is wrapped on the surface of the metal wire. The end of the microwire is used to record the discharge activity of neuronal cells. Alternatively, multiple silicon probes are used to prepare a multi-channel electrode array, which is implanted in the brain to record neural signals. In clinical practice, rigid neural electrodes such as metal microwire electrodes and silicon-based electrodes are usually used to record neural signals in the brain or peripheral areas. The elastic modulus of these rigid neural electrodes and brain tissue and neural tissue do not match, which brings a series of problems caused by mechanical mismatch, such as damage to brain tissue after implantation in the brain, causing tissue immune response, etc.

[0004] Compared with rigid materials, flexible neural electrodes have unparalleled advantages. They can not only reduce brain tissue damage and reduce the immune response of the organism, but also extend the service life of the electrode and establish a long-term stable neuro-biological interface. At present, the development directions of flexible electrodes are as follows: the first is to use flexible polymers as electrode substrates to prepare neural electrodes, such as flexible materials such as polyimide (PI) and polydimethylsiloxane (PDMS). For example, CN110367978A discloses a flexible neural electrode, including an elastic substrate, an adhesion layer, a polyimide substrate layer, a metal electrode layer and a polyimide encapsulation layer, wherein the polyimide substrate layer, the metal electrode layer and the polyimide encapsulation layer constitute a two-dimensional planar structure electrode; the adhesion layer includes a Ti layer and a SiO2 layer, the Ti layer is arranged on the surface of the polyimide substrate layer, and the SiO2 layer is arranged on the Ti layer. The SiO2 layer undergoes a condensation reaction with the elastic substrate to produce a strong chemical bond that causes the two-dimensional planar structure electrode to adhere to the surface of the elastic substrate. Through the deformation of the elastic substrate, the two-dimensional planar structure electrode forms a three-dimensional buckled structure electrode under the action of extrusion. The second is to adjust the existing neural electrode structure, design flexible electrodes of different shapes, and improve their mechanical properties. The third is to use new electrode materials, such as graphene, carbon nanotubes, conductive polymers, etc. as electrode materials to prepare flexible neural electrodes. For example, CN108577827A discloses a neural electrode, including a base electrode, the surface of which is provided with alginate gel, multi-walled carbon nanotubes and conductive polymer nanocomposite materials; the neural electrode has both the flexibility of alginate gel and the conductivity of conductive polymers, has good biocompatibility, is tightly combined with the base electrode, and can achieve relatively sensitive signal conduction.

[0005] Although flexible electrodes solve the mechanical mismatch problem between neural electrodes and brain and neural tissue, they suffer from poor mechanical properties and generally lack physical, mechanical, and electrochemical stability, making it difficult to stably record neural signals in vivo over the long term. Therefore, developing flexible electrodes with excellent mechanical properties, mechanical stability, and electrochemical stability is an urgent challenge in this field.

[0006] Summary of the Invention

[0007] The present application provides a graphene neural electrode, a preparation method thereof, and an application thereof. Through the design of laser-induced graphene, the modification of the conductive polymer layer, and the combination thereof with the process steps, the graphene neural electrode obtained by the preparation method has excellent flexibility characteristics and mechanical properties, improves the stability between biological interfaces, has high mechanical and electrochemical stability, and low electrochemical impedance, and can achieve long-term stable signal monitoring in vivo.

[0008] In a first aspect, the present application provides a method for preparing a graphene neural electrode, the method comprising the following steps:

[0009] (1) laser printing a preset electrode pattern on a polyimide film to obtain laser-induced graphene;

[0010] (2) transferring the laser-induced graphene obtained in step (1) onto a water-soluble tape, then placing a thermoplastic polymer film on the side of the laser-induced graphene away from the water-soluble tape, and then removing the water-soluble tape to transfer the laser-induced graphene onto the thermoplastic polymer film to obtain a first preform;

[0011] (3) placing the first preform obtained in step (2) in a conductive polymer monomer solution for electrochemical polymerization to form a conductive polymer layer on the surface of the laser-induced graphene to obtain a second preform; and

[0012] (4) Arranging a thermoplastic polymer encapsulation layer on the conductive polymer layer of the second preform obtained in step (3) to obtain the graphene neural electrode.

[0013] In the preparation method provided in the present application, laser-induced graphene (LIG) is prepared on a polyimide film using laser direct writing carbonization technology, and a conductive polymer layer is modified on the LIG by electrochemical polymerization. In combination with specific process steps, the LIG modified with the conductive polymer layer is embedded in a thermoplastic polymer elastomer to form an interconnected graphene nanonetwork, so that the prepared graphene neural electrode has flexible characteristics and excellent tensile properties, improves its mechanical properties, solves the problem of mechanical mismatch, can better cooperate with the deformation caused by tissue movement in the body, and reduces the damage of the electrode to the body; at the same time, the electrochemical impedance of the graphene neural electrode is significantly reduced, the sensitivity is high, and neural signals can be recorded more clearly and accurately, realizing real-time monitoring of brain neural signals; moreover, the graphene neural electrode has excellent electrochemical stability and mechanical stability, effectively improving the stability between biological interfaces, and can realize long-term and stable signal monitoring in the body.

[0014] The following are preferred technical solutions of this application, but are not intended to limit the technical solutions provided in this application. Through the following preferred technical solutions, the objectives and beneficial effects of this application can be better achieved and realized.

[0015] In this application, the preset electrode pattern can be designed through professional design software to obtain different electrode shapes. Laser direct writing carbonization technology can be used to independently realize graphene neural electrodes with different patterns according to needs, achieving a patterned effect.

[0016] Preferably, the thickness of the polyimide film is 50-200 μm, for example, it can be 60 μm, 70 μm, 80 μm, 90 μm, 100 μm, 110 μm, 120 μm, 130 μm, 140 μm, 150 μm, 160 μm, 170 μm, 180 μm or 190 μm, as well as specific point values ​​between the above point values. Due to space limitations and for the sake of simplicity, this application no longer exhaustively lists the specific point values ​​included in the range, and 100-150 μm is further preferred.

[0017] Preferably, the laser printing device is a carbon dioxide laser.

[0018] Preferably, the laser printing power is 6-12W, for example, it can be 6.5W, 7W, 7.5W, 8W, 8.5W, 9W, 9.5W, 10W, 10.5W, 11W or 11.5W, as well as specific point values ​​between the above point values. Due to space limitations and for the sake of simplicity, this application no longer exhaustively lists the specific point values ​​included in the range.

[0019] Preferably, the scanning speed of the laser printing is 200-600 mm / s, for example, it can be 250 mm / s, 300 mm / s, 350 mm / s, 400 mm / s, 450 mm / s, 500 mm / s or 550 mm / s, as well as specific point values ​​between the above point values. Due to space limitations and for the sake of simplicity, this application no longer exhaustively lists the specific point values ​​included in the range.

[0020] Preferably, the thickness of the laser-induced graphene is 30-50 μm, for example, it can be 32 μm, 33 μm, 38 μm, 40 μm, 42 μm, 45 μm or 48 μm, as well as specific point values ​​between the above point values. Due to space limitations and for the sake of simplicity, this application no longer exhaustively lists the specific point values ​​included in the range.

[0021] Preferably, the method of transferring laser-induced graphene to a water-soluble tape comprises: applying a water-soluble tape to the laser-induced graphene, peeling off the water-soluble tape after applying the tape tightly, and transferring the laser-induced graphene to the water-soluble tape.

[0022] Preferably, the thermoplastic polymer in step (2) includes any one or a combination of at least two of SEBS (hydrogenated styrene-butadiene block copolymer), SIS (styrene-isoprene-styrene block copolymer), SBS (styrene-butadiene-styrene block copolymer), SEPS (hydrogenated styrene-isoprene block copolymer), or PDMS (polydimethylsiloxane), and SEBS is further preferred.

[0023] Preferably, the method for providing the thermoplastic polymer film comprises: spin-coating a thermoplastic polymer solution on a side of the laser-induced graphene away from the water-soluble tape, and drying the solution to obtain the thermoplastic polymer film.

[0024] Preferably, the concentration of the thermoplastic polymer solution is 0.01-0.3 g / mL, for example, 0.02 g / mL, 0.05 g / mL, 0.08 g / mL, 0.1 g / mL, 0.12 g / mL, 0.15 g / mL, 0.18 g / mL, 0.2 g / mL, 0.22 g / mL, 0.25 g / mL or 0.28 g / mL, as well as specific values ​​between the above points. Due to space limitations and for the sake of brevity, this application no longer exhaustively lists the specific points included in the range, and 0.05-0.2 g / mL is further preferred.

[0025] Preferably, the solvent of the thermoplastic polymer solution is an organic solvent, illustratively including but not limited to: any one of toluene, xylene, trimethylbenzene, chlorobenzene, or a combination of at least two thereof.

[0026] Preferably, the thickness of the thermoplastic polymer film is 30-60 μm, for example, it can be 32 μm, 33 μm, 38 μm, 40 μm, 42 μm, 45 μm, 48 μm, 50 μm, 52 μm, 55 μm or 58 μm, as well as specific point values ​​between the above point values. Due to space limitations and for the sake of simplicity, this application no longer exhaustively lists the specific point values ​​included in the range.

[0027] As the preferred technical solution of the present application, step (2) adopts the method of transferring LIG with a water-soluble tape, which can prepare an ultra-thin SEBS film (30-60 μm), thereby preparing a thinner graphene neural electrode, further reducing the damage of the electrode to the organism. If the water-soluble tape transfer method is not adopted, for example, the SEBS film is directly used to transfer LIG, due to the firm adhesion between LIG and the PI film, a SEBS film of about 30 μm thickness will break during the transfer process. Therefore, it is necessary to increase the thickness of the SEBS film, and a SEBS film of about 200 μm thickness can successfully transfer LIG. A thicker SEBS film will increase the overall thickness of the LIG neural electrode, thereby increasing the damage to the tissue after implantation into the organism.

[0028] Preferably, the conductive polymer monomer solution includes 3,4-ethylenedioxythiophene and optionally a styrenesulfonic acid polymer, and more preferably a combination of 3,4-ethylenedioxythiophene and a styrenesulfonic acid polymer.

[0029] As a preferred technical solution of this application, the conductive polymer monomer solution includes a combination of EDOT and sodium polystyrene sulfonate (PSS), which is electrochemically polymerized to form PEDOT or PEDOT:PSS, thereby modifying the PEDOT conductive polymer layer on LIG. This reduces the electrochemical impedance of the graphene neural electrode, allowing for clearer and more accurate recording of neural signals, enabling real-time monitoring of brain neural signals. Furthermore, LIG ​​and PEDOT are both very stable materials. The resulting graphene neural electrode containing LIG-PEDOT has excellent electrochemical and mechanical stability, enabling long-term and stable signal monitoring in vivo.

[0030] Preferably, the conductive polymer monomer solution includes a combination of 3,4-ethylenedioxythiophene (EDOT), styrenesulfonic acid polymer (PSS) and water.

[0031] Preferably, the concentration of 3,4-ethylenedioxythiophene in the conductive polymer monomer solution is 1-30 mmol / L, for example, it can be 2 mmol / L, 5 mmol / L, 8 mmol / L, 10 mmol / L, 12 mmol / L, 15 mmol / L, 18 mmol / L, 20 mmol / L, 22 mmol / L, 25 mmol / L or 28 mmol / L, as well as specific point values ​​between the above point values. Due to space limitations and for the sake of simplicity, this application no longer exhaustively lists the specific point values ​​included in the range, and 5-20 mmol / L is further preferred.

[0032] Preferably, the styrenesulfonic acid-based polymer is selected from polystyrenesulfonic acid and / or polystyrenesulfonate, more preferably sodium polystyrenesulfonate.

[0033] Preferably, the concentration of sodium polystyrene sulfonate in the conductive polymer monomer solution is 0.01-0.5 mol / L, for example, 0.02 mol / L, 0.05 mol / L, 0.08 mol / L, 0.1 mol / L, 0.12 mol / L, 0.15 mol / L, 0.18 mol / L, 0.2 mol / L, 0.22 mol / L, 0.25 mol / L, 0.28 mol / L, 0.3 mol / L, 0.32 mol / L, 0.35 mol / L, 0.38 mol / L, 0.4 mol / L, 0.42 mol / L, 0.45 mol / L or 0.48 mol / L, as well as specific values ​​between the above points. Due to space limitations and for the sake of brevity, this application does not exhaustively enumerate the specific values ​​included in the above range, and 0.05-0.3 mol / L is further preferred.

[0034] Preferably, the voltage of the electrochemical polymerization is 0.5-1.5 V, for example, 0.6 V, 0.7 V, 0.8 V, 0.9 V, 1 V, 1.1 V, 1.2 V, 1.3 V or 1.4 V, as well as specific values ​​between the above points. Due to space limitations and for the sake of brevity, this application does not exhaustively list the specific values ​​included in the range.

[0035] Preferably, the electrochemical polymerization time is 100-1000s, for example, it can be 150s, 200s, 250s, 300s, 350s, 400s, 450s, 500s, 550s, 600s, 650s, 700s, 800s or 900s, as well as specific point values ​​between the above point values. Due to space limitations and for the sake of simplicity, this application no longer exhaustively lists the specific point values ​​included in the range, and 200-600s is further preferred.

[0036] Preferably, the method for providing the thermoplastic polymer encapsulation layer comprises: spin-coating a thermoplastic polymer solution on the conductive polymer layer, and drying the solution to obtain the thermoplastic polymer encapsulation layer.

[0037] Preferably, the thermoplastic polymer in step (4) comprises any one of SEBS, SIS, SBS, SEPS or PDMS or a combination of at least two thereof, more preferably SEBS.

[0038] As a preferred technical solution of the present application, the thermoplastic polymer in step (2) and step (4) is SEBS, so that the conductive polymer-modified LIG is embedded in the SEBS elastomer, giving the graphene neural electrode excellent tensile properties, which can better cooperate with the deformation caused by tissue movement in the body.

[0039] Preferably, the concentration of the thermoplastic polymer solution is 0.01-0.3 g / mL, for example, 0.02 g / mL, 0.05 g / mL, 0.08 g / mL, 0.1 g / mL, 0.12 g / mL, 0.15 g / mL, 0.18 g / mL, 0.2 g / mL, 0.22 g / mL, 0.25 g / mL or 0.28 g / mL, as well as specific values ​​between the above points. Due to space limitations and for the sake of brevity, this application no longer exhaustively lists the specific points included in the range, and 0.05-0.2 g / mL is further preferred.

[0040] Preferably, the solvent of the thermoplastic polymer solution is an organic solvent, illustratively including but not limited to: any one of toluene, xylene, trimethylbenzene or chlorobenzene, or a combination of at least two thereof.

[0041] Preferably, the thickness of the thermoplastic polymer encapsulation layer is 30-60 μm, for example, it can be 32 μm, 33 μm, 38 μm, 40 μm, 42 μm, 45 μm, 48 μm, 50 μm, 52 μm, 55 μm or 58 μm, as well as specific point values ​​between the above point values. Due to space limitations and for the sake of simplicity, this application no longer exhaustively lists the specific point values ​​included in the said range.

[0042] Preferably, the step of cutting and / or tailoring is further included after the thermoplastic polymer encapsulation layer is provided.

[0043] Preferably, the preparation method comprises the following steps:

[0044] (1) introducing a preset electrode pattern into a carbon dioxide laser, and performing laser printing on a polyimide film according to the preset electrode pattern, wherein the laser printing power is 6-12 W and the scanning speed is 200-600 mm / s, to obtain laser-induced graphene with a thickness of 30-50 μm;

[0045] (2) firstly applying a water-soluble tape to the laser-induced graphene obtained in step (1), peeling off the water-soluble tape after applying the tape tightly, so that the laser-induced graphene is transferred to the water-soluble tape; then, spin-coating a SEBS solution on the side of the laser-induced graphene away from the water-soluble tape, drying, and forming a SEBS film with a thickness of 30-60 μm; then, removing the water-soluble tape, so that the laser-induced graphene is transferred to the SEBS film, and obtaining a first preform;

[0046] (3) placing the first preform obtained in step (2) in a 3,4-ethylenedioxythiophene-sodium polystyrene sulfonate aqueous solution for electrochemical polymerization, wherein the voltage of the electrochemical polymerization is 0.5-1.5 V and the time is 100-1000 s, so that a conductive polymer layer is formed on the surface of the laser-induced graphene to obtain a second preform;

[0047] wherein the concentration of 3,4-ethylenedioxythiophene in the 3,4-ethylenedioxythiophene-sodium polystyrene sulfonate aqueous solution is 1-30 mmol / L, and the concentration of sodium polystyrene sulfonate is 0.01-0.5 mol / L; and

[0048] (4) Spin-coating a SEBS solution on the conductive polymer layer of the second preform obtained in step (3) and drying the solution to form a SEBS encapsulation layer with a thickness of 30-60 μm; after the encapsulation is completed, the graphene neural electrode is obtained by optionally cutting and optionally trimming the preform.

[0049] In a second aspect, the present application provides a graphene neural electrode, which is prepared using the preparation method described in the first aspect.

[0050] In a third aspect, the present application provides an application of the graphene neural electrode as described in the second aspect in an electrode array, a stress-strain sensor, a biosensor or an implantable medical device.

[0051] Exemplarily, the graphene neural electrode is used in the manufacture of stress-strain sensors and biosensors, and can be used for testing finger bending, pressure, human pulse, breathing, sound, etc.

[0052] For example, the graphene neural electrode is applied to the manufacture of biosensors to monitor neurotransmitters such as dopamine, ascorbic acid, uric acid, and adrenaline.

[0053] Compared with the prior art, this application has the following beneficial effects:

[0054] In the preparation method provided in this application, laser-induced graphene (LIG) is prepared on a polyimide film using laser direct writing carbonization technology to achieve a patterned effect; a conductive polymer layer is modified on the LIG by electrochemical polymerization, and combined with specific process steps, the LIG modified with the conductive polymer layer is embedded in a thermoplastic polymer elastomer to form an interconnected graphene nanonetwork, so that the prepared graphene neural electrode has flexible characteristics and excellent tensile properties, improves its mechanical properties, can better cooperate with the deformation caused by tissue movement in the body, and reduces the damage of the electrode to the organism. At the same time, the electrochemical impedance of the graphene neural electrode is significantly reduced, and the impedance at 1kHz is 222.26-303.25Ω·mm 2 The cathode charge storage capacity is improved, the sensitivity is high, the clarity of the signal during the recording process is improved, and the neural signals can be recorded more clearly and accurately; moreover, the graphene neural electrode has excellent electrochemical stability and mechanical stability, which effectively improves the stability between the biological interfaces, and can achieve long-term stable real-time signal monitoring in the body, and has a wide range of application scenarios. BRIEF DESCRIPTION OF THE DRAWINGS

[0055] FIG1 is a schematic diagram of a process for preparing a graphene neural electrode provided in a specific embodiment.

[0056] FIG2 is a scanning electron microscope image of a surface of the laser-induced graphene prepared in Example 1.

[0057] FIG3 is a scanning electron microscope image of another surface of the laser-induced graphene prepared in Example 1.

[0058] FIG4 is a scanning electron microscope image of the conductive polymer layer modified laser-induced graphene prepared in Example 1.

[0059] FIG5 is a cyclic voltammogram of the graphene neural electrodes provided in Example 1 and Comparative Example 1.

[0060] FIG6 is an electrochemical impedance curve diagram of the graphene neural electrodes provided in Example 1 and Comparative Example 1.

[0061] FIG7 is a cyclic voltammetry curve diagram of the graphene neural electrodes provided in Example 2 and Comparative Example 1.

[0062] FIG8 is an electrochemical impedance curve diagram of the graphene nerve electrodes provided in Example 2 and Comparative Example 1.

[0063] FIG9 is a cyclic voltammogram of the graphene neural electrodes provided in Example 3 and Comparative Example 1.

[0064] FIG10 is an electrochemical impedance curve diagram of the graphene neural electrodes provided in Example 3 and Comparative Example 1.

[0065] FIG11 is a CV curve diagram of the mechanical stability test of the graphene neural electrode provided in Example 1.

[0066] FIG12 is an EIS curve diagram of the mechanical stability test of the graphene neural electrode provided in Example 1. DETAILED DESCRIPTION

[0067] The technical solution of the present application is further described below through specific implementation methods. Those skilled in the art should understand that the embodiments are only used to help understand the present application and should not be regarded as specific limitations of the present application.

[0068] As used herein, the terms "comprises," "including," "having," "containing" or any other variations thereof, are intended to cover a non-exclusive inclusion. For example, a composition, process, method, article, or apparatus that comprises a listed element is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, process, method, article, or apparatus.

[0069] "Optionally" or "either" means that the subsequently described event or circumstance can or cannot occur, and that the description includes instances where the event occurs and instances where it does not.

[0070] The indefinite articles "a" and "an" before an element or component of the present application do not limit the quantity requirement (i.e., the number of times the element or component appears). Therefore, "a" or "an" should be interpreted as including one or at least one, and elements or components in the singular also include plural forms, unless the quantity clearly refers to only the singular form.

[0071] In this application, features defined as "first" or "second" may explicitly or implicitly include one or more of the features, and are used to distinguish and describe features, without distinction of order or importance. In the description of this application, unless otherwise specified, "plurality" means two or more.

[0072] In one embodiment, the process diagram of the graphene neural electrode preparation method is shown in FIG1 , which includes the following steps:

[0073] (1) Laser printing a preset electrode pattern on a polyimide (PI) film to obtain laser-induced graphene (LIG);

[0074] (2) transferring the LIG obtained in step (1) onto a water-soluble tape, then placing a SEBS film on the side of the laser-induced graphene away from the water-soluble tape, and then removing the water-soluble tape to transfer the laser-induced graphene onto the SEBS film to obtain a first preform;

[0075] (3) placing the first preform obtained in step (2) in a 3,4-ethylenedioxythiophene (EDOT)-sodium polystyrene sulfonate aqueous solution for electrochemical polymerization to form a conductive polymer layer PEDOT on the surface of LIG, thereby obtaining a second preform; and

[0076] (4) Spin-coating a SEBS solution on the conductive polymer layer of the second preform obtained in step (3), and obtaining a SEBS encapsulation layer after drying, thereby obtaining the graphene neural electrode (referred to as "LIG-PEDOT neural electrode").

[0077] The materials involved in the following specific implementations of this application are as follows:

[0078] (1) SEBS, brand Tuftec H1062, purchased from Asahi Kasei;

[0079] (2) Polyimide (PI) film, thickness 125 μm, brand Kaptone HN500, purchased from Dupont;

[0080] (3) Water-soluble tape, brand 5414, purchased from 3M.

[0081] Example 1

[0082] A graphene neural electrode and a preparation method thereof, the preparation method comprising the following steps:

[0083] (1) A 125 μm thick PI film was pasted on a glass plate, and the preset electrode pattern designed by the software was introduced into a CO2 laser. Laser printing was performed on the PI according to the preset electrode pattern. The laser printing power was 9 W and the scanning speed was 400 mm / s, resulting in a laser-induced graphene (LIG) with a thickness of approximately 40 μm.

[0084] (2) First, a water-soluble tape is applied to the laser-induced graphene (LIG) obtained in step (1), and the water-soluble tape is removed after being applied tightly, so that the LIG is transferred to the water-soluble tape; then, a SEBS solution (the solvent is toluene, and the concentration is 0.1 g / mL) is spin-coated on the side of the LIG away from the water-soluble tape, and after the solution evaporates and dries, a SEBS film with a thickness of about 30 μm is formed; then, the water-soluble tape is dissolved and removed with water, so that the LIG is transferred to the SEBS film, thereby obtaining a first preform;

[0085] (3) placing the first preform obtained in step (2) in a 3,4-ethylenedioxythiophene EDOT-sodium polystyrene sulfonate aqueous solution (the concentration of EDOT is 10 mmol / L, and the concentration of sodium polystyrene sulfonate is 0.1 mol / L), connecting to an electrochemical workstation and performing electrochemical polymerization at a voltage of 0.9 V for 400 s to form a conductive polymer layer PEDOT on the surface of LIG, forming PEDOT-modified LIG, thereby obtaining a second preform;

[0086] (4) Spin-coating a SEBS solution (the solvent is toluene, the concentration is 0.1 g / mL) on the conductive polymer layer of the second preform obtained in step (3) and drying to form a SEBS encapsulation layer with a thickness of about 30 μm; after the encapsulation is completed, appropriate cutting and cutting are performed to obtain the graphene neural electrode, which is recorded as "LIG-PEDOT neural electrode".

[0087] Scanning electron microscopy (SEM, JSM-7610F, JOEL and TM4000, Hitachi) was used to characterize the morphology of the LIG and PEDOT-modified LIG prepared in this example. An SEM image of one surface (front) of the laser-induced graphene is shown in Figure 2, and an SEM image of the other surface (back) is shown in Figure 3. An SEM image of the laser-induced graphene modified with a conductive polymer layer is shown in Figure 4. The SEM images show that when laser-printed onto the PI film, both the LIG and the LIG transferred onto the SEBS film exhibit a three-dimensional, porous structure. Furthermore, Figure 4 clearly shows that high polymers are formed on the LIG surface after electrochemical polymerization, indicating that PEDOT has been successfully modified onto the LIG surface, forming a stable LIG-PEDOT electrode material.

[0088] Example 2

[0089] A graphene neural electrode and a preparation method thereof, the preparation method comprising the following steps:

[0090] (1) A 125 μm thick PI film was pasted on a glass plate, and the preset electrode pattern designed by the software was introduced into a CO2 laser. Laser printing was performed on the PI according to the preset electrode pattern. The laser printing power was 9 W and the scanning speed was 400 mm / s, resulting in a laser-induced graphene (LIG) with a thickness of approximately 40 μm.

[0091] (2) First, a water-soluble tape is applied to the laser-induced graphene (LIG) obtained in step (1), and the water-soluble tape is removed after being applied tightly, so that the LIG is transferred to the water-soluble tape; then, a SEBS solution (the solvent is toluene, and the concentration is 0.1 g / mL) is spin-coated on the side of the LIG away from the water-soluble tape, and after the solution evaporates and dries, a SEBS film with a thickness of about 30 μm is formed; then, the water-soluble tape is dissolved and removed with water, so that the LIG is transferred to the SEBS film, thereby obtaining a first preform;

[0092] (3) placing the first preform obtained in step (2) in a 3,4-ethylenedioxythiophene EDOT-sodium polystyrene sulfonate aqueous solution (the concentration of EDOT is 10 mmol / L, and the concentration of sodium polystyrene sulfonate is 0.1 mol / L), connecting it to an electrochemical workstation and performing electrochemical polymerization at a voltage of 0.9 V for 300 s to form a conductive polymer layer PEDOT on the surface of LIG, forming PEDOT-modified LIG, thereby obtaining a second preform;

[0093] (4) Spin-coating a SEBS solution (the solvent is toluene, the concentration is 0.1 g / mL) on the conductive polymer layer of the second preform obtained in step (3) and drying to form a SEBS encapsulation layer with a thickness of about 30 μm; after the encapsulation is completed, appropriate cutting and cutting are performed to obtain the graphene neural electrode, which is recorded as "LIG-PEDOT neural electrode".

[0094] Example 3

[0095] A graphene neural electrode and a preparation method thereof, the preparation method comprising the following steps:

[0096] (1) A 125 μm thick PI film was pasted on a glass plate, and the preset electrode pattern designed by the software was introduced into a CO2 laser. Laser printing was performed on the PI according to the preset electrode pattern. The laser printing power was 9 W and the scanning speed was 400 mm / s, resulting in a laser-induced graphene (LIG) with a thickness of approximately 40 μm.

[0097] (2) First, a water-soluble tape is applied to the laser-induced graphene (LIG) obtained in step (1), and the water-soluble tape is removed after being applied tightly, so that the LIG is transferred to the water-soluble tape; then, a SEBS solution (the solvent is toluene, and the concentration is 0.1 g / mL) is spin-coated on the side of the LIG away from the water-soluble tape, and after the solution evaporates and dries, a SEBS film with a thickness of about 30 μm is formed; then, the water-soluble tape is dissolved and removed with water, so that the LIG is transferred to the SEBS film, thereby obtaining a first preform;

[0098] (3) placing the first preform obtained in step (2) in a 3,4-ethylenedioxythiophene EDOT-sodium polystyrene sulfonate aqueous solution (the concentration of EDOT is 10 mmol / L and the concentration of sodium polystyrene sulfonate is 0.1 mol / L), connecting to an electrochemical workstation and performing electrochemical polymerization at a voltage of 0.9 V for 500 s to form a conductive polymer layer PEDOT on the surface of LIG, forming PEDOT-modified LIG, and obtaining a second preform;

[0099] (4) Spin-coating a SEBS solution (the solvent is toluene, the concentration is 0.1 g / mL) on the conductive polymer layer of the second preform obtained in step (3) and drying to form a SEBS encapsulation layer with a thickness of about 30 μm; after the encapsulation is completed, appropriate cutting and cutting are performed to obtain the graphene neural electrode, which is recorded as "LIG-PEDOT neural electrode".

[0100] Comparative Example 1

[0101] A graphene neural electrode and a preparation method thereof, the preparation method comprising the following steps:

[0102] (1) A 125 μm thick PI film was pasted onto a glass plate. The preset electrode pattern designed by the software was introduced into a CO2 laser. The preset electrode pattern was laser printed on the PI at a power of 9 W and a scanning speed of 400 mm / s, resulting in a LIG film with a thickness of approximately 40 μm.

[0103] (2) First, a water-soluble tape is applied to the LIG obtained in step (1), and after being applied tightly, the water-soluble tape is removed to transfer the LIG to the water-soluble tape; then, a SEBS solution (the solvent is toluene, the concentration is 0.1 g / mL) is spin-coated on the side of the LIG away from the water-soluble tape, and after the solution evaporates and dries, a SEBS film with a thickness of approximately 30 μm is formed; then, the water-soluble tape is dissolved and removed with water to transfer the LIG to the SEBS film, thereby obtaining a first preform;

[0104] (3) Spin-coating a SEBS solution (the solvent is toluene, the concentration is 0.1 g / mL) on the side of the first preform obtained in step (2) away from the SEBS film, and drying to form a SEBS encapsulation layer with a thickness of about 30 μm; after the encapsulation is completed, appropriate cutting and cutting are performed to obtain the graphene neural electrode, which is recorded as "LIG neural electrode".

[0105] The performance of the graphene neural electrodes provided in Examples 1-3 and Comparative Example 1 was tested as follows:

[0106] (1) Electrochemical performance and stability test

[0107] Electrochemical tests, including electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV), were performed on the electrodes in phosphate-buffered saline (PBS) buffer. Electrochemical experiments were conducted using a Reference 600 electrochemical workstation (GAMRY) and a six-electrode system. The graphene neural electrode served as the working electrode, a platinum wire as the counter electrode, and a saturated calomel electrode (SCE) as the reference electrode. All electrochemical tests were performed at 25°C.

[0108] Figure 5 shows cyclic voltammograms of the graphene neural electrodes provided in Example 1 and Comparative Example 1, respectively showing the cyclic voltammogram of the LIG-PEDOT neural electrode provided in Example 1, the cyclic voltammogram of Example 1 after 100 cycles, and the cyclic voltammogram of the LIG neural electrode provided in Comparative Example 1. The potential range was -0.4 V to 0.6 V, and the scan rate was 50 mV / s. Compared to the unmodified PEDOT LIG neural electrode in Comparative Example 1, the LIG-PEDOT neural electrode provided in Example 1 exhibited significantly higher peak current, a larger cyclic voltammogram area, and a 162.12-fold increase in cathode charge storage, indicating superior electrochemical performance. Furthermore, Example 1 maintained its excellent cyclic voltammogram after 100 cycles, with no significant decrease in cathode charge storage, indicating excellent electrochemical stability.

[0109] FIG6 is an electrochemical impedance curve diagram of the graphene neural electrodes provided in Example 1 and Comparative Example 1, showing the electrochemical impedance curve of the LIG-PEDOT neural electrode provided in Example 1, the electrochemical impedance curve of Example 1 after 100 cycles, and the electrochemical impedance curve of the LIG neural electrode provided in Comparative Example 1. As can be seen from FIG6 , compared with Comparative Example 1, the impedance of the LIG-PEDOT neural electrode provided in Example 1 at 1 kHz is significantly reduced to 230.45 Ω·mm 2, decreased by 91.63%, indicating that the sensitivity of the LIG-PEDOT neural electrode is good, which effectively improves the clarity of the signal during the recording process and can record neural signals more clearly and accurately; moreover, the impedance of Example 1 after 100 CV cycles did not change significantly, and the electrochemical stability was excellent.

[0110] Figure 7 shows the cyclic voltammograms of the graphene neural electrodes provided in Example 2 and Comparative Example 1, respectively. The potential range is -0.4 V to 0.6 V, and the scan rate is 50 mV / s. Compared to the unmodified PEDOT LIG neural electrode in Comparative Example 1, the LIG-PEDOT neural electrode provided in Example 2 exhibits significantly higher peak current, a larger cyclic voltammogram area, and a 60.47-fold increase in cathode charge storage, resulting in superior electrochemical performance.

[0111] FIG8 is an electrochemical impedance curve diagram of the graphene neural electrodes provided in Example 2 and Comparative Example 1, respectively showing the electrochemical impedance curve of the LIG-PEDOT neural electrode provided in Example 2 and the electrochemical impedance curve of the LIG neural electrode provided in Comparative Example 1. As can be seen from FIG8 , compared with Comparative Example 1, the impedance of the LIG-PEDOT neural electrode provided in Example 2 at 1 kHz is significantly reduced to 303.25 Ω·mm 2 , decreased by 88.99%, indicating that the LIG-PEDOT neural electrode has good sensitivity, effectively improves the clarity of the signal during the recording process, and can record neural signals more clearly and accurately.

[0112] Figure 9 shows the cyclic voltammograms of the graphene neural electrodes provided in Example 3 and Comparative Example 1, respectively. The potential range is -0.4 V to 0.6 V, and the scan rate is 50 mV / s. Compared to the unmodified PEDOT LIG neural electrode in Comparative Example 1, the LIG-PEDOT neural electrode provided in Example 3 exhibits significantly higher peak current, a larger cyclic voltammogram area, and a 144.74-fold increase in cathode charge storage, resulting in superior electrochemical performance.

[0113] FIG10 is an electrochemical impedance curve diagram of the graphene neural electrodes provided in Example 3 and Comparative Example 1, respectively showing the electrochemical impedance curve of the LIG-PEDOT neural electrode provided in Example 3 and the electrochemical impedance curve of the LIG neural electrode provided in Comparative Example 1. As can be seen from FIG10 , compared with Comparative Example 1, the impedance of the LIG-PEDOT neural electrode provided in Example 3 at 1 kHz is significantly reduced to 222.26 Ω·mm2 , a decrease of 91.93%, indicating that the LIG-PEDOT neural electrode has good sensitivity, effectively improves the clarity of the signal during the recording process, and can record neural signals more clearly and accurately.

[0114] 2. Mechanical stability test

[0115] The electrodes to be tested were treated in ultrasound for 1 min, 5 min, and 10 min, respectively. The CV test and EIS test of the electrodes before and after ultrasound treatment were performed using the same method as in “Electrochemical Performance and Stability Test”.

[0116] Figure 11 is a CV curve diagram of the mechanical stability test of the graphene neural electrode provided in Example 1, and Figure 12 is an EIS curve diagram of the mechanical stability test of the graphene neural electrode provided in Example 1. According to Figures 11 and 12, the LIG-PEDOT neural electrode provided in Example 1 was subjected to an ultrasonic test to simulate the microscopic damage of the electrode in the biological body. The results showed that there was no significant decrease in the cathode charge storage and impedance before and after ultrasonic treatment; combined with the test results of Figures 5 and 6, neither 100 CV cycles nor ultrasonic treatment had a significant effect on the impedance and cathode charge storage of the LIG-PEDOT neural electrode, indicating that the LIG-PEDOT neural electrode provided in this application has excellent electrochemical and mechanical stability, verifying its feasibility of long-term recording in the biological body.

[0117] The applicant declares that while the above-described embodiments are used to illustrate the graphene neural electrodes, their preparation methods, and applications, this application is not limited to the aforementioned process steps, nor does it imply that implementation of this application requires reliance on these process steps. Persons skilled in the art should understand that any improvements to this application, equivalent substitutions for the raw materials used, additions of auxiliary components, and selection of specific methods, etc., fall within the scope of protection and disclosure of this application.

Claims

1. A method for preparing a graphene neural electrode, comprising the following steps: (1) Laser printing is performed on a polyimide film according to a preset electrode pattern to obtain laser-induced graphene; (2) The laser-induced graphene obtained in step (1) is transferred to a water-soluble tape, then a thermoplastic polymer film is provided on the side of the laser-induced graphene away from the water-soluble tape, and then the water-soluble tape is removed, so that the laser-induced graphene is transferred to the thermoplastic polymer film to obtain a first preform; (3) The first preform obtained in step (2) is placed in a conductive polymer monomer solution for electrochemical polymerization, so that a conductive polymer layer is formed on the surface of the laser-induced graphene to obtain a second preform; and (4) A thermoplastic polymer encapsulation layer is provided on the conductive polymer layer of the second preform obtained in step (3) to obtain the graphene neural electrode.

2. The preparation method according to claim 1, wherein, The device for laser printing is a carbon dioxide laser; Preferably, the power of the laser printing is 6 - 12 W; Preferably, the scanning speed of the laser printing is 200 - 600 mm / s; Preferably, the thickness of the laser-induced graphene is 30 - 50 μm.

3. The preparation method according to claim 1 or 2, wherein, The method for transferring the laser-induced graphene onto the water-soluble tape includes: attaching the water-soluble tape onto the laser-induced graphene, and after pressing tightly, peeling off the water-soluble tape to transfer the laser-induced graphene onto the water-soluble tape.

4. The preparation method according to any one of claims 1-3, wherein, The thermoplastic polymer in step (2) includes any one or a combination of at least two of SEBS, SIS, SBS, SEPS, and PDMS, preferably SEBS; Preferably, the method for setting the thermoplastic polymer film includes: spin-coating a thermoplastic polymer solution on the side of the laser-induced graphene away from the water-soluble tape, and drying to obtain the thermoplastic polymer film; Preferably, the concentration of the thermoplastic polymer solution is 0.01 - 0.3 g / mL, and more preferably 0.05 - 0.2 g / mL; Preferably, the thickness of the thermoplastic polymer film is 30 - 60 μm.

5. The preparation method according to any one of claims 1-4, wherein, The conductive polymer monomer solution includes a combination of 3,4-ethylenedioxythiophene, styrenesulfonic acid-based polymer, and water; Preferably, the concentration of 3,4-ethylenedioxythiophene in the conductive polymer monomer solution is 1 - 30 mmol / L, and more preferably 5 - 20 mmol / L; Preferably, the styrenesulfonic acid-based polymer is selected from polystyrenesulfonic acid and / or polystyrenesulfonate, and more preferably sodium polystyrenesulfonate; Preferably, the concentration of sodium polystyrenesulfonate in the conductive polymer monomer solution is 0.01 - 0.5 mol / L, and more preferably 0.05 - 0.3 mol / L.

6. The preparation method according to any one of claims 1-5, wherein, The voltage for the electrochemical polymerization is 0.5 - 1.5 V; Preferably, the time for the electrochemical polymerization is 100 - 1000 s, and more preferably 200 - 600 s.

7. The preparation method according to any one of claims 1-6, wherein, The method for setting the thermoplastic polymer encapsulation layer includes: spin-coating a thermoplastic polymer solution on the conductive polymer layer, and drying to obtain the thermoplastic polymer encapsulation layer; Preferably, the thermoplastic polymer in step (4) includes any one or a combination of at least two of SEBS, SIS, SBS, SEPS, and PDMS, and more preferably SEBS; Preferably, the thickness of the thermoplastic polymer encapsulation layer is 30 - 60 μm; Preferably, after setting the thermoplastic polymer encapsulation layer, it further includes steps of cutting and / or trimming.

8. The preparation method according to any one of claims 1-7, wherein, The preparation method includes the following steps: (1) Importing a preset electrode pattern into a carbon dioxide laser, and performing laser printing on the polyimide film according to the preset electrode pattern, where the power of the laser printing is 6 - 12 W, the scanning speed is 200 - 600 mm / s, to obtain laser-induced graphene with a thickness of 30 - 50 μm; (2) First, attach the water-soluble tape to the laser-induced graphene obtained in step (1). After pressing it tightly, peel off the water-soluble tape to transfer the laser-induced graphene onto the water-soluble tape. Then, spin-coat the SEBS solution on the side of the laser-induced graphene away from the water-soluble tape and dry it to form an SEBS film with a thickness of 30 - 60 μm. Next, remove the water-soluble tape to transfer the laser-induced graphene onto the SEBS film, obtaining the first preform; (3) Place the first preform obtained in step (2) in an aqueous solution of 3,4-ethylenedioxythiophene-sodium polystyrene sulfonate for electrochemical polymerization. The voltage of the electrochemical polymerization is 0.5 - 1.5 V and the time is 100 - 1000 s, so as to form a conductive polymer layer on the surface of the laser-induced graphene, obtaining the second preform; The concentration of 3,4-ethylenedioxythiophene in the aqueous solution of 3,4-ethylenedioxythiophene-sodium polystyrene sulfonate is 1 - 30 mmol / L, and the concentration of sodium polystyrene sulfonate is 0.01 - 0.5 mol / L; (4) Spin-coat the SEBS solution on the conductive polymer layer of the second preform obtained in step (3) and dry it to form an SEBS encapsulation layer with a thickness of 30 - 60 μm; After encapsulation, through optional cutting and optional trimming steps, the graphene nerve electrode is obtained.

9. A graphene nerve electrode prepared by the preparation method according to any one of claims 1-8.

10. Use of a graphene nerve electrode according to claim 9 in an electrode array, a stress-strain sensor, a biosensor or an implantable medical device.

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