Biocompatible flexible carbon-based physiological electrode prepared by coaxial spinning and application of biocompatible flexible carbon-based physiological electrode

Abstract

The invention relates to the technical field of flexible bioelectronics and biomedical sensors, in particular to a biocompatible flexible carbon-based physiological electrode prepared through coaxial spinning and application of the biocompatible flexible carbon-based physiological electrode. The conductive core is formed by crosslinking graphene oxide, carbon nanotubes and the like; the buffer layer contains polyurethane and the like, and shape memory microspheres and antibacterial nano-silver are added; a biological interface layer contains chitosan and the like, and PEG-PE is grafted to reduce protein adsorption; the thickness ratio of the three layers is 1: (1.5-2): (0.5-1), and the thickness is 100-300 microns; the electrode has conductive, sensing and antibacterial functions, can load double enzymes for blood glucose monitoring, is strong in interlayer bonding, and is suitable for various biomedical scenes. By innovating the three-layer structure and the material design, high conductivity, high flexibility and excellent biocompatibility are achieved; multi-parameter monitoring and electrical stimulation treatment can be achieved, the anti-bending performance is good, the antibacterial and anticoagulant effects are good, the preparation process is controllable, and the application prospects in the fields of wearable equipment, implantation medical treatment and the like are wide.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of flexible bioelectronic and biomedical sensors, in particular to a coaxial spinning prepared biocompatible flexible carbon-based physiological electrode and application thereof. BACKGROUND

[0002] In the field of biomedical monitoring and treatment, physiological electrodes, as the core devices for acquiring human electrical signals (such as electrocardiogram, electroencephalogram, electromyogram) and implementing electrical stimulation treatment, their performance directly affects the diagnostic accuracy and treatment effect. Traditional physiological electrodes mostly use metal materials (such as silver / silver chloride electrode) or rigid carbon materials, which have defects such as poor biocompatibility, mismatching mechanical properties with human tissues, etc. Metal electrodes can easily cause skin allergy and inflammatory reaction, and signal attenuation due to ion migration in long-term use; rigid carbon electrodes have certain conductivity, but lack flexibility, which cannot adapt to the dynamic deformation of the skin or organ surface, causing unstable signal acquisition, and even damage to the tissue.

[0003] With the development of flexible electronic technology, flexible physiological electrodes have gradually become a research hotspot. Existing flexible electrodes are mainly prepared by solution coating, compression molding and other processes, which have problems such as single structure and low functional integration. For example, electrodes based on polydimethylsiloxane (PDMS) and carbon nanomaterials, although flexible, have unevenly dispersed conductive networks, resulting in low electrode conductivity (<10 S / cm) and large resistance fluctuation during stretching; single-component fiber electrodes prepared by electrospinning are difficult to achieve high conductivity, biocompatibility and mechanical cushioning performance at the same time, and cannot meet the long-term stable use requirements in complex physiological environment.

[0004] At the interface between the electrode and the biological interface, existing technologies face many challenges. Protein adsorption and cell adhesion on the surface of the electrode will cause signal interference and inflammatory reaction, affecting the monitoring accuracy and use safety; for implantable electrodes, there is a lack of effective antibacterial and anti-inflammatory function, which easily causes infection risk. In addition, traditional electrodes have single function, which can only realize electrical signal acquisition, and cannot meet the demand of multi-parameter monitoring (such as blood glucose, hydrogen peroxide concentration) and electrical stimulation treatment coordination, limiting their application in wearable medical devices and implantable medical devices.

[0005] Although there have been studies to improve electrode performance through material modification and structural optimization, there are still limitations. Most studies only improve a single performance, such as improving biocompatibility through surface coating or enhancing conductivity by adding conductive fillers, lacking systematic innovative design of electrode materials, structures and functions. In terms of preparation process, the existing technology is difficult to accurately control the interface bonding of multi-layer structure and the uniform dispersion of nanoscale functional units, resulting in unstable electrode performance and large batch difference. Therefore, it is urgent to develop a flexible physiological electrode with high conductivity, biocompatibility, mechanical adaptability and multi-functional integration and its preparation technology to meet the growing clinical needs and technological upgrading requirements in the biomedical field. SUMMARY

[0006] (I) Technical problems solved

[0007] In view of the deficiencies of the prior art, the present application provides a coaxial spinning prepared biocompatible flexible carbon-based physiological electrode and its application.

[0008] (II) Technical solutions

[0009] A coaxial spinning prepared biocompatible flexible carbon-based physiological electrode, the electrode comprises a three-layer structure from inside to outside:

[0010] The innermost layer is a conductive core formed by cross-linking reaction of graphene oxide, carbon nanotubes, polypyrrole, 1-butyl-3-methylimidazolium hexafluorophosphate, bisphenol A diglycidyl ether and benzoyl peroxide to form a conductive network; the structural formula of 1-butyl-3-methylimidazolium hexafluorophosphate is:

[0011]

[0012] The structural formula of bisphenol A diglycidyl ether is:

[0013]

[0014] The structural formula of benzoyl peroxide is:

[0015]

[0016] The middle layer is a buffer layer composed of polyurethane, polycaprolactone, gelatin, glycerol and nano-silver particles; the outermost layer is a biological interface layer composed of chitosan, hyaluronic acid, polydopamine, RGD sequence integrin binding peptide and triacetin, and the thickness ratio of the three layers is 1:(1.5-2):(0.5-1), and the overall thickness is 100-300 μm.

[0017] Preferably, it also includes uniformly dispersed porphyrin iron complex Fe-TPP in the conductive core, and the content is 0.5-2 parts.

[0018] Preferably, the buffer layer also includes shape memory polyurethane microspheres introduced in the buffer layer, with a content of 5-10 parts, a phase transition temperature of 40-45℃, and a particle size of 5-20μm.

[0019] Preferably, the bio-interface layer further includes polyethylene glycol-modified phosphatidylethanolamine (PEG-PE) grafted via click chemistry, with a grafting density of [missing information]. .

[0020] Preferably, a transition layer formed by dopamine self-polymerization is provided between the conductive core and the buffer layer, with a thickness of 50-200 nm, and gold nanoparticles with a diameter of 2-5 nm are uniformly distributed in the transition layer.

[0021] Preferably, the electrode surface is further loaded with glucose oxidase (GOx) and horseradish peroxidase (HRP), with enzyme loadings of respectively... Within the glucose concentration range of 1-20 mmol / L, the current response sensitivity is... .

[0022] Preferably, the method for preparing the biocompatible flexible carbon-based physiological electrode includes the following steps:

[0023] S1: Preparation of conductive core spinning solution

[0024] Graphene oxide was dispersed in N,N-dimethylformamide and sonicated for 2-4 hours. Carbon nanotubes were added and sonicated for 1-2 hours. Then, polypyrrole, ionic liquid, porphyrin iron complex, crosslinking agent and initiator were mixed and stirred at 300-500 rpm for 1-2 hours for degassing treatment.

[0025] S2: Preparation of buffer layer spinning solution

[0026] Polyurethane and polycaprolactone were dissolved in a dichloromethane / acetone mixed solvent, and gelatin, glycerin, nano-silver particles and shape memory polyurethane microspheres were added. The mixture was ultrasonically dispersed for 30-60 min and stirred at 200-400 rpm for 1-2 h.

[0027] S3: Preparation of bio-interface layer spinning solution

[0028] After chitosan is dissolved in acetic acid solution, hyaluronic acid, polydopamine, integrin-binding peptide and PEG-PE are added in sequence. Stir at 150-300 rpm to dissolve and add plasticizer.

[0029] S4: Coaxial spinning forming

[0030] The three-layer spinning solution is extruded through a coaxial nozzle and coagulated in an ethanol / water solution containing 5-10% calcium chloride. The coagulation bath temperature is 10-15℃, and the solution is left to stand for 3-5 minutes. After washing with water, the solution is removed.

[0031] S5: Post-processing

[0032] The electrode is heat treated at 60-80℃ with a temperature rising rate of 5℃ / min for 1-2h, immersed in an ethanol solution containing 5-20mg / mL dexamethasone, loaded with the drug at 25℃ and 50rpm for 24-48h, and then pre-dried at a vacuum degree of <10Pa and 40℃ for 2h.

[0033] Preferably, in the S4 coaxial spinning process, a 5-10kV direct current electric field is applied by the nozzle to make the carbon nanotubes directionally arrange along the electric field direction, with an orientation degree of 0.85-0.95, and a 1-2T magnetic field is applied on the surface of the receiving device to make the gold nanoparticles uniformly distribute in the transition layer.

[0034] Preferably, in the S5 post-processing, the electrode is immersed in a PBS solution containing 0.1-0.5% glutaraldehyde for cross-linking for 1-2h, and then sequentially immersed in enzyme solutions of GOx and HRP, to load the double enzymes through physical adsorption and covalent binding, with the enzyme solution concentrations being 1-5mg / mL and 0.5-3mg / mL, respectively.

[0035] Preferably, the biocompatible flexible carbon-based physiological electrode is applied in a wearable continuous blood glucose monitoring system, an implantable nerve signal recording device, a motor rehabilitation muscle electric stimulation treatment, and a chronic wound healing monitoring and electrotherapy.

[0036] (Three) Beneficial technical effects

[0037] Compared with the prior art, the beneficial effects of the present application are:

[0038] 1. The introduction of porphyrin iron complex and directionally arranged carbon nanotubes into the conductive core improves the electrode conductivity and provides hydrogen peroxide catalytic response capability, which can be used for biomarker detection; the embedding of shape memory polyurethane microspheres into the buffer layer endows the electrode with excellent stability of resistance change rate, and the nano-silver particles provide antibacterial protection; the PEG-PE grafting and double enzyme loading of the biological interface layer significantly reduce protein adsorption, realize continuous blood glucose monitoring, and the sensitivity reaches .

[0039] 2. The stability of electrode signal acquisition is improved; the interlayer bonding strength is higher than that of traditional flexible electrodes, effectively avoiding delamination. In addition, the dexamethasone loaded on the surface of the electrode can be released for more than 14 days, and the anticoagulant properties of PEG-PE reduce the risk of infection in the implantation scene, while the cell adhesion rate remains good.

[0040] 3. The coaxial spinning combined with electric field-magnetic field synergistic regulation realizes the precise orientation and uniform dispersion of nanomaterials; the click chemistry grafting and double enzyme loading technology ensures the stable modification of functional molecules. This process can realize the batch production of electrodes, with a performance difference coefficient of <5% between batches, meeting the industrialization needs.

[0041] 4. The electrode can be widely used in wearable medical devices, implantable monitoring systems and electrical stimulation therapy fields. In continuous blood glucose monitoring, the detection range covers 1-20 mmol / L, and the error is ≤3%; when used for muscle electrical stimulation rehabilitation, the stimulation intensity can be adjusted in real time according to the electromyographic signal, and the treatment efficiency is improved. BRIEF DESCRIPTION OF DRAWINGS

[0042] Fig. 1 is a flow chart of a preparation method of a coaxial spinning prepared biocompatible flexible carbon-based physiological electrode disclosed by the application;

[0043] Fig. 2 is a comparison chart of the electrical conductivity and the resistance change rate after bending 500 times of the examples and the comparative examples;

[0044] Fig. 3 is a comparison chart of the protein adsorption amount of the examples and the comparative examples;

[0045] Fig. 4 is a radar comparison chart of the basic performance parameters of the examples and the comparative examples after being unified in dimension. DETAILED DESCRIPTION

[0046] According to Figs. 1 to 4 , the specific embodiments of the application are as follows:

[0047] I. Material and instrument preparation

[0048] 1. Experimental materials

[0049] Conductive core raw materials: graphene oxide (flake diameter 2-3 μm, Nanjing Xianfeng Nanometer), single-walled carbon nanotube (tube diameter 15-25 nm, length 8-12 μm), polypyrrole (electrical conductivity 60 S / cm), 1-butyl-3-methyl imidazole hexafluorophosphate, bisphenol A diglycidyl ether, benzoyl peroxide, iron porphyrin complex (Fe-TPP), N,N-dimethylformamide (DMF, analytical pure).

[0050] Buffer layer raw materials: polyurethane (Shore hardness 85A), polycaprolactone (molecular weight 60,000 Da), gelatin (250 Bloom), glycerol, nano-silver particles (particle size 30 nm), shape memory polyurethane microspheres (phase transition temperature 42℃, particle size 8-15 μm), dichloromethane (chromatographic pure), acetone (chromatographic pure).

[0051] Biological interface layer raw materials: chitosan (degree of deacetylation 92%), hyaluronic acid (molecular weight 2 million Da), polydopamine, RGD sequence integrin binding peptide, polyethylene glycol phosphatidylethanolamine (PEG-PE, molecular weight 5000 Da), triglyceride, 2% acetic acid solution.

[0052] Functional load raw materials: dexamethasone, glucose oxidase (GOx, ≥100 U / mg), horseradish peroxidase (HRP, ≥250 U / mg), glutaraldehyde (25% aqueous solution).

[0053] 2. Instrumentation

[0054] Ultrasonic cell disruptor (power 1200 W), rotary evaporator, custom three-axis coaxial spinning machine (inner diameter of nozzle: inner layer 0.3 mm, middle layer 0.7 mm, outer layer 1.2 mm), vacuum drying oven, fluorescence microscope, electrochemical workstation (CHI660E), scanning electron microscope (SEM).

[0055] II. Example 1: Preparation of physiological electrode by standard process

[0056] Preparation of conductive core spinning solution

[0057] Disperse 35 g of graphene oxide in 1000 mL of DMF and ultrasonic for 4 hours until uniform; add 25 g of carbon nanotubes and continue to ultrasonic for 2 hours. Add 20 g of polypyrrole, 8 g of 1-butyl-3-methylimidazolium hexafluorophosphate, 3 g of Fe-TPP, 4 g of bisphenol A diglycidyl ether, and 1.5 g of benzoyl peroxide in sequence, stir at 300 rpm for 2 hours, and vacuum degassing for 30 minutes to prepare a spinning solution with a viscosity of 100 mPa·s.

[0058] Preparation of buffer layer spinning solution

[0059] Dissolve 45 g of polyurethane and 25 g of polycaprolactone in 1200 mL of dichloromethane / acetone (2:1, v / v) mixed solvent. Add 15 g of gelatin, 8 g of glycerol, 1 g of silver nanoparticles, and 8 g of shape memory polyurethane microspheres, ultrasonic dispersion for 45 minutes, and stir at 200 rpm for 1.5 hours to prepare a spinning solution with a viscosity of 100 mPa·s.

[0060] Preparation of biological interface layer spinning solution

[0061] Dissolve 35 g of chitosan in 1500 mL of 2% acetic acid solution, and add 20 g of hyaluronic acid, 8 g of polydopamine, 0.3 g of RGD peptide, and 3 g of PEG-PE in sequence. After stirring and dissolving, add 4 g of triacetin and stir at 150 rpm for 2 hours to prepare a spinning solution with a viscosity of 100 mPa·s.

[0062] Coaxial spinning forming

[0063] ​​​Three layers of spinning solution were injected into the nozzle respectively, and the flow rates were set as follows: 1.2 mL / h for the conductive core, 1.5 mL / h for the buffer layer, and 1.0 mL / h for the biological interface layer. The spinning was performed under the conditions of an electric field strength of 12 kV and a receiving distance of 15 cm, and the fibers were dropped into a coagulation bath containing 8% calcium chloride in ethanol / water (1:1) at 12°C, and were taken out after staying for 4 minutes and washed with deionized water for 3 times.

[0064] Post-processing

[0065] The electrode was heat-treated at 70°C for 1.5 hours, and was immersed in a 10 mg / mL dexamethasone ethanol solution to load the drug under the condition of 25°C and 50 rpm oscillation for 48 hours. After vacuum drying, the product was prepared by immersing it in a 0.3% glutaraldehyde PBS solution for cross-linking for 1.5 hours, and then sequentially immersing it in 5 mg / mL GOx and 3 mg / mL HRP solutions for 2 hours each.

[0066] III. Example 2: Optimization of blood glucose monitoring performance

[0067] Preparation of conductive core spinning solution

[0068] 35 g of graphene oxide was dispersed in 1000 mL of DMF and ultrasonically treated for 4 hours until uniform; 25 g of carbon nanotubes was added and ultrasonically treated for another 2 hours. 20 g of polypyrrole, 8 g of 1-butyl-3-methylimidazolium hexafluorophosphate, 1.8 g of Fe-TPP, 4 g of bisphenol A diglycidyl ether, and 1.5 g of benzoyl peroxide were sequentially added, stirred at 300 rpm for 2 hours, and vacuum degassed for 30 minutes to prepare a spinning solution with a viscosity of 800 mPa·s.

[0069] Preparation of buffer layer spinning solution

[0070] The same as in Example 1: 45 g of polyurethane and 25 g of polycaprolactone were dissolved in 1200 mL of a mixed solvent of dichloromethane / acetone (2:1, v / v), 15 g of gelatin, 8 g of glycerol, 1 g of nano-silver particles, and 8 g of shape memory polyurethane microspheres were added, ultrasonically dispersed for 45 minutes, and stirred at 200 rpm for 1.5 hours to prepare a spinning solution with a viscosity of 1200 mPa·s.

[0071] Preparation of biological interface layer spinning solution

[0072] The same as in Example 1: 35 g of chitosan was dissolved in 1500 mL of a 2% acetic acid solution, 20 g of hyaluronic acid, 8 g of polydopamine, 0.3 g of RGD peptide, and 3 g of PEG-PE were sequentially added, stirred and dissolved, 4 g of triacetin was added, and stirred at 150 rpm for 2 hours to prepare a spinning solution with a viscosity of 600 mPa·s.

[0073] Coaxial spinning molding

[0074] Three layers of the spinning solution were injected into the nozzle respectively, and the flow rate was maintained at 1.2 mL / h for the conductive core, 1.5 mL / h for the buffer layer, and 1.0 mL / h for the biological interface layer. An auxiliary electric field of 8 kV was applied to the nozzle, and the receiving distance was 15 cm. The fibers fell into a coagulation bath containing 8% calcium chloride in ethanol / water (1:1) at 12°C, and were taken out after staying for 4 minutes. They were washed with deionized water for 3 times.

[0075] Post-processing

[0076] The electrode was heat-treated at 70°C for 1.5 hours, and then was immersed in a 10 mg / mL dexamethasone ethanol solution for 48 hours at 25°C with 50 rpm oscillation to load the drug. After vacuum drying, the product was prepared by immersing it in a 0.3% glutaraldehyde PBS solution for cross-linking for 1.5 hours, and then sequentially immersing it in 8 mg / mL GOx and 5 mg / mL HRP solutions for 2 hours each.

[0077] Four, Example 3: Scale-up production verification

[0078] Preparation of conductive core spinning solution (10 times the amount of raw materials)

[0079] 350 g of graphene oxide was dispersed in 10000 mL of DMF and ultrasonically treated for 4 hours until uniform; 250 g of carbon nanotubes was added and ultrasonically treated for another 2 hours. 200 g of polypyrrole, 80 g of 1-butyl-3-methylimidazolium hexafluorophosphate, 30 g of Fe-TPP, 40 g of bisphenol A diglycidyl ether, and 15 g of benzoyl peroxide were added in sequence, stirred at 300 rpm for 2 hours, and vacuum degassed for 30 minutes to prepare a spinning solution with a viscosity of 800 mPa·s.

[0080] Preparation of buffer layer spinning solution (10 times the amount of raw materials)

[0081] 450 g of polyurethane and 250 g of polycaprolactone were dissolved in 12000 mL of dichloromethane / acetone (2:1, v / v) mixed solvent. 150 g of gelatin, 80 g of glycerol, 10 g of silver nanoparticles, and 80 g of shape memory polyurethane microspheres were added, ultrasonically dispersed for 45 minutes, and stirred at 200 rpm for 1.5 hours to prepare a spinning solution with a viscosity of 1200 mPa·s.

[0082] Preparation of biological interface layer spinning solution (10 times the amount of raw materials)

[0083] 350 g of chitosan was dissolved in 15000 mL of 2% acetic acid solution, and 200 g of hyaluronic acid, 80 g of polydopamine, 3 g of RGD peptide, and 30 g of PEG-PE were added in sequence. After stirring and dissolving, 40 g of triacetin was added, and the mixture was stirred at 150 rpm for 2 hours to prepare a spinning solution with a viscosity of 600 mPa·s.

[0084] Coaxial spinning forming (5 batches of continuous production)

[0085] The above 10 times amount of three-layer spinning solution was injected into the industrialized spinning equipment liquid storage tank, and 5 batches were continuously produced according to the following parameters:

[0086] Flow rate: 1.2 mL / h for conductive core, 1.5 mL / h for buffer layer, and 1.0 mL / h for biological interface layer (single nozzle parameter, multiple nozzles working in parallel)

[0087] Electric field strength: 12 kV

[0088] Receiving distance: 15 cm

[0089] Coagulation bath conditions: 8% calcium chloride in ethanol / water (1:1) solution at 12°C, and the fiber stays for 4 minutes

[0090] Washing: Each batch of fiber is washed with deionized water for 3 times before entering the drying process

[0091] Post-processing (batch processing)

[0092] Each batch of electrode is sequentially treated in a 70°C oven for 1.5 hours. Soak in 100 mg / mL dexamethasone ethanol solution (total amount is scaled up proportionally), 25°C, 50 rpm oscillation for 48 hours. After vacuum drying, immerse in 3% glutaraldehyde PBS solution for crosslinking for 1.5 hours, and then sequentially immerse in 50 mg / mL GOx and 30 mg / mL HRP solutions for 2 hours each.

[0093] Example V: Traditional single-layer carbon-based electrode

[0094] Mix carbon nanotubes (20g) with PDMS (80g), add curing agent and stir uniformly; coat on PET substrate, cure at 60°C for 2 hours; spray chitosan solution on the surface and dry.

[0095] Basic performance parameters of the example and the comparative example are compared as follows:

[0096] Table 1

[0097]

[0098] The electrode conductivity of the example of the present application reaches 120-135 S / cm, the bending stability is excellent (resistance change rate ≤13%), the interlayer strength is more than 20 N / cm, and the protein adsorption amount is <5 μg / cm²; the conductivity of the comparative example is only 12 S / cm, the stability is poor and the protein adsorption is high, which proves that the material and structure design of the present application significantly improves the comprehensive performance.

[0099] The blood glucose monitoring performance of the example and the comparative example is compared as follows:

[0100] Table 2

[0101]

[0102] Example 1-2 Electrodes achieve 0.5-20mmol / L wide-range blood glucose monitoring by optimizing enzyme loading and carbon nanotube orientation, with sensitivity up to Detection limit as low as 0.5mmol / L; Comparative Example without enzyme loading, no blood glucose response, verifying effectiveness of functionalization design.

[0103] While embodiments of the application have been shown and described, it is to be understood that the embodiments described are only by way of example and that changes, modifications, substitutions and alterations can be made thereto without departing from the spirit and scope of the application as defined in the following claims, in which:

Claims

1. A biocompatible flexible carbon-based physiological electrode prepared by coaxial spinning, characterized in that, The electrode comprises a three-layer structure from inside to outside: The innermost layer is a conductive core formed by cross-linking reaction of graphene oxide, carbon nanotubes, polypyrrole, 1-butyl-3-methylimidazolium hexafluorophosphate, bisphenol A diglycidyl ether and benzoyl peroxide to form a conductive network; The middle layer is a buffer layer composed of polyurethane, polycaprolactone, gelatin, glycerol and nano-silver particles; and the outermost layer is a biological interface layer composed of chitosan, hyaluronic acid, polydopamine, RGD sequence integrin binding peptide and triacetin, with a thickness ratio of 1:(1.5-2):(0.5-1) and a total thickness of 100-300μm.

2. The biocompatible, flexible, carbon-based physiological electrode according to claim 1, wherein, The conductive core further comprises uniformly dispersed porphyrin iron complex Fe-TPP in an amount of 0.5-2 parts.

3. The biocompatible, flexible, carbon-based physiological electrode according to claim 1, wherein, The buffer layer further comprises introduced shape memory polyurethane microspheres in an amount of 5-10 parts, with a phase transition temperature of 40-45℃ and a particle size of 5-20μm.

4. The biocompatible, flexible, carbon-based physiological electrode according to claim 1, wherein, The biological interface layer further comprises a polyethyleneglycolated phosphatidylethanolamine PEG-PE grafted by click chemistry, the grafting density being .

5. The biocompatible, flexible, carbon-based physiological electrode according to claim 1, wherein, A transition layer formed by self-polymerization of dopamine is arranged between the conductive core and the buffer layer, with a thickness of 50-200nm and uniformly distributed gold nanoparticles with a diameter of 2-5nm.

6. The biocompatible, flexible, carbon-based physiological electrode according to claim 1, wherein, The electrode surface is also loaded with glucose oxidase GOx and horseradish peroxidase HRP, and the enzyme loadings are respectively and In the glucose concentration range of 1-20 mmol / L, the current response sensitivity is .

7. The biocompatible, flexible, carbon-based physiological electrode according to any one of claims 1 to 6, wherein the carbon-based material is a carbon nanotube. The preparation method comprises the following steps: S1: preparing a conductive core spinning solution Disperse graphene oxide in N,N-dimethylformamide under ultrasonic for 2-4h, add carbon nanotubes and ultrasonic for 1-2h, then mix polypyrrole, ionic liquid, porphyrin iron complex, cross-linking agent and initiator, stir at 300-500rpm for 1-2h and perform defoaming treatment; S2: preparing a buffer layer spinning solution Dissolve polyurethane and polycaprolactone in dichloromethane / acetone mixed solvent, add gelatin, glycerol, nano-silver particles and shape memory polyurethane microspheres, ultrasonic dispersion for 30-60min and stirring at 200-400rpm for 1-2h; S3: preparing a biological interface layer spinning solution Dissolve chitosan in acetic acid solution, then add hyaluronic acid, polydopamine, integrin binding peptide and PEG-PE in sequence, stir and dissolve at 150-300rpm and add plasticizer; S4: coaxial spinning forming The three-layer spinning solution is extruded through a coaxial nozzle, coagulated in an ethanol / water solution containing 5-10% calcium chloride, with a coagulation bath temperature of 10-15℃ and a residence time of 3-5min, then taken out after water washing; S5: post-processing Heat treat the electrode at 60-80℃ with a heating rate of 5℃ / min for 1-2h, immerse in an ethanol solution containing 5-20mg / mL dexamethasone, load the drug at 25℃ and 50rpm for 24-48h, and then pre-dry at a vacuum degree of <10Pa and a temperature of 40℃ for 2h.

8. The biocompatible, flexible, carbon-based physiological electrode according to claim 7, wherein, During the coaxial spinning process in S4, apply a direct current electric field of 5-10kV to the nozzle to make the carbon nanotubes directionally arrange along the electric field direction, with an orientation degree of 0.85-0.95, and apply a magnetic field of 1-2T to the receiving device surface to make the gold nanoparticles uniformly distribute in the transition layer.

9. The biocompatible, flexible, carbon-based physiological electrode according to claim 7, wherein, In S5 post-processing, the electrode 0.1-0.5% glutaraldehyde is first immersed in PBS solution containing 1-2h cross-linking, and then sequentially immersed in enzyme solutions of GOx and HRP, and the double enzymes are loaded by physical adsorption and covalent binding, and the enzyme solution concentrations are 1-5mg / mL and 0.5-3mg / mL respectively.

10. The use of the biocompatible flexible carbon-based physiological electrode according to any one of claims 1-9 in wearable continuous glucose monitoring systems, implantable nerve signal recording devices, motor rehabilitation muscle electrical stimulation therapy, and chronic wound healing monitoring and electrotherapy.

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