CN115624336B - Nuclear magnetic compatible nerve electrical stimulation-electrical recording system and preparation method thereof - Google Patents
Nuclear magnetic compatible nerve electrical stimulation-electrical recording system and preparation method thereof Download PDFInfo
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Abstract
The invention belongs to the field of medical appliances, and particularly relates to a nuclear magnetic compatible nerve electrical stimulation-electrical recording system and a preparation method thereof. The invention forms a fiber nerve electrode by wet spinning of conductive polymer solution, then carries out insulation treatment on the fiber nerve electrode, and then is connected with a printed circuit board to obtain the nuclear magnetic compatible nerve electrical stimulation-electrical recording system. The fiber nerve electrode prepared by the invention has low impedance, high charge injection and storage capacity and excellent nuclear magnetic compatibility. The assembled nerve electrical stimulation-electrical recording system can obtain the full brain complete functional nuclear magnetic resonance image, and simultaneously can carry out multichannel nerve electrical stimulation and electrophysiological recording in the animal brain, thereby providing an effective platform for multi-modal observation of brain activities and having great application potential in brain science research and diagnosis and treatment of brain diseases.
Description
Technical Field
The invention belongs to the field of medical appliances, and particularly relates to a nuclear magnetic compatible nerve electrical stimulation-electrical recording system and a preparation method thereof.
Background
With the continuous development of brain science and the rising of brain plans of various countries, scientists have conducted intensive studies on brain working mechanisms, pathogenesis and diagnosis and treatment means, and effective detection of multi-scale signals in the brain through various means is the basis for developing the studies.
Currently, neural activity observers of different temporal spatial resolutions including implantable neural electrodes, cortical electroencephalography, positron emission computed tomography, and functional magnetic resonance imaging have been developed. However, a single means cannot achieve high time and spatial resolution at the same time, and it is difficult to obtain a correlation mechanism of various signals, so that comprehensive explanation and judgment of brain diseases are affected. In order to solve the above problems, researchers combine different-scale neural activity observation means and develop a multi-mode neural activity detection technology, wherein the development of a functional nuclear magnetism-electroencephalogram combined technology is mature, but the two detection technologies covering the whole brain still cannot achieve higher spatial resolution. The combination of functional magnetic resonance imaging technology with implanted nerve electrodes can solve the problem, and the functional activity of the whole brain can be observed while the specific brain region is subjected to electric stimulation/electric signal recording.
The traditional implanted nerve electrode can generate serious nuclear magnetic artifacts due to electromagnetic interaction in a nuclear magnetic environment to destroy nuclear magnetic resonance images, so that normal observation of brain region activities of an implanted part is influenced. Researchers have developed nuclear magnetic compatible neural electrodes based on metal alloys, carbon materials, and others. On one hand, because the magnetic susceptibility of the used materials still has a large difference with that of human tissues, the generated artifacts still affect the integrity of the whole brain imaging; on the other hand, the developed electrode only realizes simultaneous electrical stimulation on the brain in the nuclear magnetic environment, and does not realize the closed loop of electrical stimulation-electrophysiological recording in the nuclear magnetic environment, but the closed loop system has pioneering significance for researching the special response of a specific brain area to the electrical stimulation, and the intervention, diagnosis and treatment and pathogenesis of diseases such as epilepsy, autism and the like. Therefore, the preparation of the multi-mode nerve activity monitoring system which can perform closed-loop electric stimulation-electrophysiological recording on a specific brain region and can perform functional nuclear magnetic resonance imaging at the same time to obtain a complete brain region moving image without artifacts is a technical problem to be solved.
Disclosure of Invention
The invention aims to provide a nuclear magnetic compatible nerve electrical stimulation-electrical recording system and a preparation method thereof, which are used for solving the problem that the existing implanted nerve electrode cannot perform closed loop electrical stimulation-electrophysiological recording on a specific brain region in a nuclear magnetic environment. Because the fiber nerve electrode prepared by the invention has good electrochemical performance and nuclear magnetic compatibility, the nerve electrical stimulation-electrical recording system formed based on the assembly of the fiber nerve electrode can be implanted into the brain of a rat for nuclear magnetic resonance imaging-electrical stimulation-electrophysiological recording.
The invention is realized by the following technical scheme:
a nuclear magnetic compatible nerve electric stimulation-electric recording system and a preparation method thereof are provided, wherein a nuclear magnetic compatible fiber nerve electrode is formed by conducting polymer solution through wet spinning, twisting and solution post-treatment, then the fiber nerve electrode is connected with a printed circuit board after insulation treatment, and finally the nuclear magnetic compatible nerve electric stimulation-electric recording system is assembled.
Further, the preparation steps of the nuclear magnetic compatible fiber neural electrode are as follows: (1) preparation of a conductive polymer spinning solution. Heating and evaporating water in the conductive polymer poly (3, 4-ethylenedioxythiophene) -poly (styrenesulfonic acid) aqueous dispersion liquid, continuously stirring, concentrating to a mass fraction of 2.0-10.0%, then adding a small amount of dimethyl sulfoxide, rapidly magnetically stirring for 2h, filtering by using a water system filter with the thickness of 0.45 mu m, and removing bubbles from the filtrate in a room temperature vacuum drying oven to obtain a conductive polymer spinning stock solution; (2) preparing a fiber electrode by wet spinning and post-treatment: comprises the steps of conducting polymer spinning dope wet spinning, fiber electrode cleaning, fiber electrode drying, fiber electrode twisting and solution treatment.
Further, the specific process for preparing the fiber electrode by wet spinning is as follows: extruding the spinning solution in the step (1) into a coagulating bath through a microinjection pump by using a 16-32G dispensing needle at a flow rate of 20-50 mu L/min to solidify and shape a fiber electrode, wherein the coagulating bath is a mixed solution of isopropanol and dimethyl sulfoxide, and then soaking and cleaning the mixed solution with deionized water to remove the residual coagulating bath components on the surface; expanding the cleaned fiber electrode to a straightened state, naturally airing at room temperature, and twisting a plurality of spirals according to the requirement to obtain a cross-sectional area with adjustable size for electric stimulation and electric recording; the twisted fiber is soaked in a mixed solution of poly (3, 4-ethylenedioxythiophene) -poly (styrenesulfonic acid) aqueous dispersion liquid and glycerin with the mass ratio of 1:1-20:1 for 20 minutes, and then taken out, and dried at room temperature, so that the nuclear magnetic compatible fiber nerve electrode is obtained.
The insulation treatment of the fiber electrode comprises two schemes of fluororubber insulation treatment and polymer film insulation treatment, and the specific steps are as follows:
(1) Fluororubber insulation treatment
Dissolving fluororubber with the mass fraction of 10-20% in 4-methyl-2-pentanone solution, stirring at 50-80 ℃ until the fluororubber is completely dissolved, immersing the nuclear-magnetic compatible fiber nerve electrode prepared in the first step into the solution, rapidly drawing out, and airing to form an elastic fluororubber insulating layer on the surface of the fiber;
(2) Insulation treatment of polymer film
Placing the fiber nerve electrode into a vapor deposition box, adding a parylene monomer, setting the deposition temperature to be 500-800 ℃, vacuumizing to 5-20 millitorr, and depositing a layer of parylene film on the fiber.
The nuclear magnetic compatible nerve electrical stimulation-electrical recording system comprises a nerve electrical stimulation-electrical recording system based on a hard printed circuit board and a nerve electrical stimulation-electrical recording system based on a flexible printed circuit board, and the specific preparation method comprises the following steps:
(1) The nerve electrical stimulation-electrical recording system based on a hard printed circuit board adopts the structure that the positive and negative sides of the hard printed circuit board are correspondingly and uniformly distributed with the same number of electrode contact pads, and the other end of the circuit board is provided with an interface for connecting with an external circuit; the fiber nerve electrodes with corresponding numbers are used as electric stimulation electrodes and are respectively connected with a copper wire reference electrode through conductive silver colloid and a circuit board front electrode contact pad; the other end of the fiber electrode exceeds the circuit board by at least 1.5cm, polyethylene glycol melted at 120-140 ℃ is adhered to an auxiliary implantation carrier by coating, and after the polyethylene glycol is rapidly solidified, a combined fiber stimulating electrode is formed, and the combined fiber electrode and the circuit board are kept on the same plane and perpendicular to the side edge of the circuit board; the other end of the reference electrode is reserved for being connected with an external circuit; covering the electrode connection pad with silicon rubber to realize insulation; correspondingly, a corresponding number of fiber nerve electrodes are used as electric recording electrodes, are connected with the back of the circuit board in the same mode with a copper wire grounding electrode and are adhered to an auxiliary implantation carrier to form a combined fiber recording electrode, and the two combined fiber electrodes are kept at a certain distance and parallel to each other according to the requirement of implantation positions, so that the nuclear magnetic compatible nerve electric stimulation-electric recording system based on the hard printed circuit board is prepared.
(2) The nerve electrical stimulation-electrical recording system based on the flexible printed circuit board adopts polyimide as a base material, takes a strip shape, has an implantation end and a connection end at two ends, wherein the implantation end is close to the front and back surfaces of the inner electrode plate, and the same number of electrode contact pads are correspondingly and uniformly distributed on the front and back surfaces of the inner electrode plate; the fiber nerve electrodes with corresponding numbers are used as electric stimulation electrodes and are connected with the contact pads of the front electrode of the circuit board through conductive silver colloid; at least 1.5cm beyond the circuit board at the other end of the fiber electrode, melting polyethylene glycol at 120-140 ℃, using the polyethylene glycol as a binder to adhere the fiber electrode to an auxiliary implantation carrier to form a combined fiber stimulating electrode, and keeping the tip of the fiber electrode aligned with the tip of the auxiliary implantation carrier, and keeping the combined fiber electrode and the circuit board on the same plane and perpendicular to the side edge of the circuit board; covering the electrode connection pad with silicon rubber to realize insulation; correspondingly, a corresponding number of fiber nerve electrodes are used as electric recording electrodes, are connected with the back of the circuit board in the same mode and adhered to the auxiliary implantation carrier to form a combined fiber recording electrode, and the two combined fiber electrodes are kept at a certain distance and parallel to each other according to the requirement of the implantation position, so that the nuclear magnetic compatible nerve electric stimulation-electric recording system based on the flexible printed circuit board is prepared.
Further, the auxiliary implantation carrier comprises an auxiliary implantation tungsten filament and an auxiliary implantation gelatin fiber, and the auxiliary implantation tungsten filament comprises the following components:
(1) The method comprises the steps of (1) auxiliary implanting tungsten wires, arranging two tungsten wires in parallel between electrode contact pads of a circuit board at a certain interval, and fixing the tungsten wires on the circuit board by using molten polyethylene glycol as an adhesive to keep the tungsten wires and the circuit board on the same plane and perpendicular to the side edges of the circuit board;
(2) Auxiliary implantation of gelatin fiber, mixing gelatin solid and deionized water in a volume ratio of 1:10-10:1, heating and dissolving at 100-160 ℃ to obtain a viscous aqueous solution of gelatin, rapidly stretching the viscous solution before solidification to obtain gelatin fiber, and naturally airing at room temperature; and arranging two gelatin fibers in parallel between electrode contact pads of the circuit board at a certain interval and fixing the positions, and keeping the gelatin fibers and the circuit board on the same plane and perpendicular to the side edges of the circuit board.
The invention has the beneficial effects that:
(1) The prepared polymer fiber neural electrode has the magnetic susceptibility similar to biological tissues, so that good nuclear magnetic compatibility is ensured, obvious artifacts are not generated in a nuclear magnetic environment after the electrode is implanted into the brain of a rat, and the acquisition of a complete functional nuclear magnetic resonance image is not influenced; the polymer fiber nerve electrode also has good flexibility and electrochemical performance, ensures that serious immune response is not induced after the polymer fiber nerve electrode is implanted into the brain, and can perform high-quality nerve electrical stimulation and electrical recording.
(2) The prepared nuclear magnetic compatible nerve electrical stimulation-electrical recording system can be implanted into the brain of an animal to perform functional nuclear magnetic resonance imaging-electrical stimulation-electrical recording, solves the technical problem of brain science research in the aspect of simultaneously performing multi-mode nerve activity monitoring, and provides an effective platform for researching pathogenesis, diagnosis and intervention of brain diseases.
Drawings
FIG. 1 is a schematic illustration of a wet spinning and fiber finishing process;
FIG. 2 is a schematic diagram of a fluororubber insulation process;
FIG. 3 is a schematic diagram of an insulation process for a polymer film;
FIG. 4 is an image of artifacts of a nuclear magnetic resonance compatible nerve electrode under nuclear magnetic resonance conditions;
FIG. 5 is a neural electro-stimulation-electrographic system (front and back) based on a rigid printed circuit board;
FIG. 6 is a flexible printed circuit board based neuro-electrical stimulation-recording system (front and back);
FIG. 7 shows that the fibrous nerve electrode of examples 1-3 has a high charge injection capacity (10-20 mC/cm 2);
FIG. 8 is a graph showing that the fibrous nerve electrode of examples 1-3 has a charge storage capacity exceeding 1000mC/cm 2;
FIG. 9 shows that the fibrous nerve electrode of examples 1-3 has a magnetic susceptibility similar to that of human tissue;
FIG. 10 shows the distribution of NeuN cells around the electrodes after implantation of the fibrous nerve electrodes in the body in examples 1-3 without significant immune response.
Detailed Description
The following describes in further detail the embodiments of the present invention with reference to examples and drawings. The following examples and figures are illustrative of the invention and are not intended to limit the scope of the invention.
Example 1 preparation of hard printed Circuit Board based Nuclear magnetic compatible neuro-electro-stimulation-electrographic System
(1) Preparing a conductive polymer spinning solution. 2g of an aqueous dispersion of the conductive polymer poly (3, 4-ethylenedioxythiophene) -poly (styrenesulfonic acid) was evaporated with constant stirring at 50℃on a hot plate and concentrated to a mass fraction of 2.0%. Then, a small amount of dimethyl sulfoxide was added and mixed, followed by rapid magnetic stirring for two hours, and then filtration was performed with a 0.45 μm aqueous filter. And (3) removing bubbles from the filtered solution in a vacuum drying oven at room temperature to obtain the conductive polymer spinning stock solution.
(2) Wet spinning and post-treatment of the fiber electrode. 1mL of the spinning solution prepared in the step (1) is taken in a disposable syringe and placed in a microinjection pump. Connecting a syringe needle with a hollow silica gel hose, connecting the other end of the hose with a 16G dispensing needle, extruding spinning solution into a coagulating bath by a micro injection pump at a flow of 20 mu L/min for wet spinning, placing the coagulating bath into a 500mL flask, soaking and cleaning the molded fiber in deionized water for 1h, and removing the coagulating bath components remained on the surface; the cleaned fiber electrode is unfolded to be in a straightened state, and naturally dried at room temperature. And (3) helically twisting 6 fiber electrodes with the same length, soaking the fiber electrodes in a solution of uniformly mixing poly (3, 4-ethylenedioxythiophene) -poly (styrenesulfonic acid) aqueous dispersion with glycerol for 20min, taking out the fiber electrodes, and airing the fiber electrodes at room temperature to obtain the nuclear magnetic compatible fiber nerve electrode.
(3) The fiber electrode is insulated by a polymer film layer. Placing the fiber nerve electrode prepared in the step (2) into a vapor deposition box, adding PARYLENE C monomers, setting the deposition temperature to be 600 ℃, vacuumizing to 5 millitorr, and depositing a PARYLENE C film with the thickness of about 2 mu m on the fiber.
(4) Assembly of a neurostimulation-electrographic system based on a rigid printed circuit board. The front and back sides of the hard circuit board are correspondingly and uniformly provided with 4 electrode contact pads, and the other end of the circuit board is provided with an interface for connecting with an external circuit; gelatin solid and deionized water are mixed according to the volume ratio of 3:1, placing the gelatin into a glass bottle, heating and dissolving the gelatin at 100 ℃ to obtain a viscous water solution of gelatin, rapidly stretching the viscous water solution immediately before solidification to obtain gelatin fibers, and naturally airing the gelatin fibers at room temperature; 2 gelatin fibers are arranged in parallel between electrode contact pads of the circuit board at a distance of 1.7mm, and the positions of the gelatin fibers exceed the side edge of the circuit board by 1.5cm and are fixed, so that the gelatin fibers and the circuit board are kept in the same plane and are vertical to the side edge of the circuit board; the 3 fiber nerve electrodes are used as electric stimulation electrodes and are respectively connected with a copper wire reference electrode with the diameter of 600 mu m through conductive silver colloid and a circuit board front electrode contact pad in sequence; melting polyethylene glycol to viscous liquid at 120 ℃, adhering the parts of the other ends of the 3 fiber electrodes beyond the circuit board to a gelatin fiber in a straightened state through polyethylene glycol liquid, keeping the electrodes aligned with the tips of the gelatin fiber, and forming a combined fiber stimulating electrode after the polyethylene glycol is rapidly solidified, wherein the other ends of the reference electrodes are reserved for being connected with an external circuit; covering the electrode connection pad with silicon rubber to realize insulation; correspondingly, 3 fiber nerve electrodes are used as electric recording electrodes and are connected with the back of the circuit board in the same manner with a copper wire grounding electrode, and are adhered to another gelatin fiber to form a combined fiber recording electrode, so that the nuclear magnetic compatible nerve electric stimulation-electric recording system based on the hard printed circuit board is prepared.
Example 2 preparation of hard printed Circuit Board based Nuclear magnetic compatible Multi-brain nerve Electrical stimulation-electrographic System
(1) Preparing a conductive polymer spinning solution, evaporating water from 4g of conductive polymer poly (3, 4-ethylenedioxythiophene) -poly (styrenesulfonic acid) aqueous dispersion on a hot table at 80 ℃, continuously stirring, concentrating to 10% by mass, adding a small amount of dimethyl sulfoxide, mixing, rapidly magnetically stirring for two hours, filtering by using a water system filter with the diameter of 0.45 mu m, and removing bubbles from the filtered solution in a vacuum drying oven at room temperature to obtain the conductive polymer spinning solution.
(2) Wet spinning and post-treatment of a fiber electrode, namely placing 1mL of spinning solution in a disposable injector in a microinjection pump, connecting a needle head of the injector with a hollow silica gel hose, connecting the other end of the hose with a 32G dispensing needle, extruding the spinning solution into a coagulating bath at a flow rate of 50 mu L/min by the microinjection pump to carry out wet spinning, placing the coagulating bath in a 500mL flask, soaking and cleaning the molded fiber in deionized water for 1h, and removing residual coagulating bath components on the surface; the washed fiber electrode is unfolded to be in a straightened state, naturally dried at room temperature, 12 fiber electrodes with the same length are twisted in a spiral way, soaked in a solution which is prepared by uniformly mixing poly (3, 4-ethylenedioxythiophene) -poly (styrenesulfonic acid) aqueous dispersion liquid and glycerol for 20min and then taken out, and dried at room temperature, so that the nuclear-magnetic compatible fiber nerve electrode is obtained.
(3) The fiber electrode is insulated by a polymer film layer, the fiber nerve electrode prepared in the step (2) is placed into a vapor deposition box, PARYLENE C monomers are added, the deposition temperature is set to be 700 ℃, the vacuum is pumped to 5 millitorr, and a PARYLENE C film with the thickness of about 4 mu m is deposited on the fiber.
(4) Based on the assembly of the nerve electrical stimulation-electrical recording system of the hard printed circuit board, the front and back surfaces of the hard circuit board are correspondingly and uniformly provided with 8 electrode contact pads, and the other end of the circuit board is provided with an interface for being connected with an external circuit; gelatin solid and deionized water are mixed according to the volume ratio of 3:1, placing the gelatin into a glass bottle, heating and dissolving the gelatin at 160 ℃ to obtain a viscous water solution of gelatin, rapidly stretching the viscous water solution immediately before solidification to obtain gelatin fibers, and naturally airing the gelatin fibers at room temperature; 3 gelatin fibers are arranged between electrode contact pads of the circuit board in parallel at a distance of 1.7mm, and the positions of the gelatin fibers exceed the side edge of the circuit board by 1.5cm and are fixed, so that the gelatin fibers and the circuit board are kept to be in the same plane and perpendicular to the side edge of the circuit board; a total of 5 bundles of electrodes are formed, each bundle comprises 3 fiber electrodes, 2 of the fiber electrodes are stimulation loops, 1 fiber electrode is a recording channel, and a copper wire reference electrode with the diameter of 600 mu m is sequentially connected with a circuit board front electrode contact pad through conductive silver colloid respectively; melting polyethylene glycol to viscous liquid at 120 ℃, adhering the parts of the other ends of the 3 fiber electrodes beyond the circuit board to a tungsten wire in a straightened state through the polyethylene glycol melt, keeping the electrodes aligned with the tips of the tungsten wire, and forming a combined fiber stimulation electrode after the polyethylene glycol is rapidly solidified, wherein the other ends of the reference electrodes are reserved for being connected with an external circuit; covering the electrode connection pad with silicon rubber to realize insulation; correspondingly, 3 fiber nerve electrodes serving as electric recording electrodes and a copper wire grounding electrode are connected with the back of the circuit board in the same mode and adhered to another gelatin fiber to form a combined fiber recording electrode, and the nuclear magnetic compatible multi-brain-area nerve electric stimulation-electric recording system based on the hard printed circuit board is prepared.
Example 3 preparation of Nuclear magnetic compatible neuro-electro-stimulation-electrographic System based on Flexible printed Circuit Board
(1) Preparing a conductive polymer spinning solution, evaporating water from 3g of conductive polymer poly (3, 4-ethylenedioxythiophene) -poly (styrenesulfonic acid) aqueous dispersion on a hot table, continuously stirring, concentrating to 3% by mass, adding a small amount of dimethyl sulfoxide, mixing, rapidly magnetically stirring for 2h, filtering by a water system filter with the diameter of 0.45 mu m, and removing bubbles from the filtered solution in a vacuum drying oven at room temperature to obtain the conductive polymer spinning solution.
(2) Wet spinning and post-treatment of the fiber electrode, taking 1mL of spinning solution in a disposable injector, and placing a microinjection pump. The syringe needle is connected with a hollow silica gel hose, the other end of the hose is connected with a 32G dispensing needle, the spinning solution is extruded into coagulation bath at the flow of 30 mu L/min, and then the formed fiber is soaked in deionized water and washed for 1 hour, so that the residual coagulation bath components on the surface are removed; the washed fiber electrode is unfolded to be in a straightened state, naturally dried at room temperature, 12 fiber electrodes with the same length are twisted in a spiral way, soaked in a solution which is prepared by uniformly mixing poly (3, 4-ethylenedioxythiophene) -poly (styrenesulfonic acid) aqueous dispersion liquid and glycerol for 20 minutes and then taken out, and the fiber electrode with nuclear magnetic compatibility is obtained after being dried at room temperature.
(3) The fiber electrode is insulated by fluororubber, the fluororubber is dissolved in 4-methyl-2-pentanone solution, and the solution is stirred at 80 ℃ until the fluororubber is completely dissolved, thus obtaining transparent viscous solution with the mass fraction of 20%. Immersing the fiber nerve electrode prepared in the step (2) into the solution, rapidly drawing the fiber nerve electrode, and forming an elastic fluororubber insulating layer on the surface of the fiber after airing.
(4) The nerve electrical stimulation-electrical recording system based on the flexible printed circuit board is assembled by taking polyimide as a base material, taking a strip shape, arranging 3 click contact pads on the front and back surfaces of an electrode plate at the inner side of the implantation end correspondingly and uniformly at two ends of the flexible printed circuit board respectively, wherein the middle pad is in a hollow circular ring shape for placing skull nails, and an interface is arranged at the connecting end of the circuit board and is connected with an external circuit; arranging two tungsten wires in parallel between electrode contact pads of a circuit board at a distance of 1.7mm, wherein the distance exceeds the side edge of the circuit board by 1.5cm, and the tungsten wires are fixed at a position, keep the tungsten wires and the circuit board in the same plane and are perpendicular to the side edge of the circuit board; 3 fiber nerve electrodes are used as electric stimulation electrodes and are sequentially connected with a contact pad of a front electrode of the circuit board through conductive silver paste; melting polyethylene glycol to viscous liquid at 120 ℃, adhering the parts of the other ends of the 3 fiber electrodes beyond the circuit board to a tungsten wire in a straightened state through polyethylene glycol liquid, keeping the electrodes aligned with the tips of the tungsten wire, and forming a combined fiber stimulation electrode after the polyethylene glycol is rapidly solidified, wherein the other ends of the reference electrodes are reserved for being connected with an external circuit; covering the electrode connection pad with silicon rubber to realize insulation; correspondingly, 3 fiber nerve electrodes are used as electric recording electrodes, are connected with the back of the circuit board in the same mode and are adhered to tungsten wires to form a combined fiber recording electrode, and the nuclear magnetic compatible nerve electric stimulation-electric recording system based on the flexible printed circuit board is prepared.
Example 4
Electrochemical characterization was performed using an electrochemical workstation (CHI 660E, CH Instruments). A PEDOT electrode, ag/AgCl wire and platinum wire immersed in PBS (0.01 m, ph=7.4) were used as the working electrode, reference electrode and counter electrode, respectively. And in the voltage range of-0.6V, the scanning speed is 0.1V/s, and the cyclic voltammogram is obtained. Calculated as a time integral of the cathodic current recorded in the second period over the potential range of-0.6 to 0.6V, the result is shown in figure 8.
The above examples are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above examples, and any other changes, modifications, substitutions, combinations, and simplifications that do not depart from the spirit and principle of the present invention should be made in the equivalent manner, and the embodiments are included in the protection scope of the present invention.
Claims (8)
1. A fiber nerve electrode is characterized in that firstly, conducting polymer spinning solution is subjected to wet spinning, twisting and solution post-treatment to form a nuclear magnetic compatible fiber nerve electrode;
the preparation method comprises the following specific steps:
Step (1): preparing a conductive polymer spinning solution, namely heating, evaporating and concentrating conductive polymer poly (3, 4-ethylenedioxythiophene) -poly (styrenesulfonic acid) aqueous dispersion until the mass fraction is 2.0-10.0%, adding dimethyl sulfoxide, uniformly mixing, and then filtering and defoaming to obtain the conductive polymer spinning solution;
step (2): preparing a fiber electrode by wet spinning and post-treatment, firstly, carrying out wet spinning on a conductive polymer spinning solution to obtain the fiber electrode, and then, cleaning, drying, twisting and solution treatment on the fiber electrode;
The specific preparation process of the fiber electrode in the step (2) comprises the following steps: extruding the conductive polymer spinning solution prepared in the step (1) into a coagulating bath through a 16-32G dispensing needle by a microinjection pump to exchange solvents, and solidifying and molding to obtain primary fibers; the coagulating bath is a mixed solution of isopropanol and dimethyl sulfoxide; then soaking and cleaning the primary fiber with deionized water to remove water-soluble impurities; then spreading the primary fiber to a straightened state, naturally airing at room temperature, and twisting a plurality of spirals according to the requirement to obtain a fiber electrode with adjustable size; finally, soaking the twisted primary fiber in a mixed solution of poly (3, 4-ethylenedioxythiophene) -poly (styrenesulfonic acid) aqueous dispersion liquid and glycerol for post-treatment; and airing the treated fiber at room temperature to obtain the nuclear-magnetic compatible fiber nerve electrode.
2. The fiber nerve electrode according to claim 1, wherein the fiber nerve electrode is subjected to insulation treatment and then connected with a printed circuit board, and finally assembled to obtain the nuclear magnetic compatible nerve electrical stimulation-electrical recording system.
3. The neurostimulation-electrographic system of claim 2, wherein the insulation treatment protocol comprises two types: fluororubber insulation treatment and polymer film insulation treatment;
When the treatment scheme is fluororubber insulation treatment, the specific steps are as follows: dispersing fluororubber in a 4-methyl-2-pentanone solution in a mass fraction of 5-20%, then immersing a fiber nerve electrode in the solution and rapidly drawing out, wherein different fluororubber concentrations correspond to different drawing-out speeds; after the fiber is dried, an elastic fluororubber insulating layer is formed on the surface of the fiber;
when the treatment scheme is polymer film insulation treatment, the specific steps are as follows: placing the fiber nerve electrode into a vapor deposition box, adding a parylene (PARYLENE C) monomer, and depositing a layer of parylene (PARYLENE C) film on the fiber; setting the deposition temperature to 500-800 ℃, and vacuumizing to 5-20 millitorr.
4. The nerve electrical stimulation-electrical recording system of claim 2, comprising two types: one is a neural electro-stimulation-electrical recording system based on a rigid printed circuit board, and the other is a neural electro-stimulation-electrical recording system based on a flexible printed circuit board.
5. The nerve electrical stimulation-electrical recording system according to claim 4, wherein when the system is a nerve electrical stimulation-electrical recording system based on a hard printed circuit board, the same number of electrode contact pads are uniformly arranged on the front and back surfaces of the adopted hard printed circuit, and an interface is arranged at the other end of the circuit board so as to be connected with an external circuit; the fiber nerve electrodes with corresponding numbers are used as electric stimulation electrodes and are respectively connected with a copper wire reference electrode through conductive silver colloid and a circuit board front electrode contact pad; the other end of the fiber electrode exceeds the circuit board by at least 1.5 cm, is adhered to an auxiliary implantation carrier together through a bio-soluble solidified polymer polyethylene glycol to form a combined fiber stimulating electrode, and keeps the tip of the fiber electrode aligned with the tip of the auxiliary implantation carrier, and keeps the combined fiber electrode and the circuit board in the same plane and vertical to the side edge of the circuit board; the other end of the reference electrode is reserved for being connected with an external circuit; covering the electrode connection pads with silicone rubber to insulate; correspondingly, the fiber nerve electrodes with corresponding numbers are used as electric recording electrodes, are connected with the back of the circuit board in the same manner with a copper wire grounding electrode and are adhered to another auxiliary implantation carrier to form a combined fiber recording electrode; the two combined fiber electrodes keep a certain distance according to the requirement of the implantation position and are parallel to each other, so that the nuclear magnetic compatible nerve electrical stimulation-electrical recording system based on the hard printed circuit board is prepared.
6. The nerve electrical stimulation-electrical recording system according to claim 4, wherein when the system is a nerve electrical stimulation-electrical recording system based on a flexible printed circuit board, the flexible printed circuit board is a polyimide substrate, and has a strip shape, and two ends are respectively an implantation end and a connection end; the electrode contact pads with the same number are correspondingly and uniformly distributed on the front and back sides of the electrode plate close to the inner side of the implantation end, wherein one pad at the middle position adopts a hollow circular ring shape for placing skull nails, and the connection end of the circuit board is provided with an interface to be connected with an external circuit; the fiber nerve electrodes with corresponding numbers are used as electric stimulation electrodes and are connected with the contact pads of the front electrode of the circuit board through conductive silver colloid; the other end of the fiber electrode exceeds the circuit board by at least 1.5 cm, is adhered to an auxiliary implantation carrier together through a bio-soluble solidified polymer polyethylene glycol to form a combined fiber stimulating electrode, and keeps the tip of the fiber electrode aligned with the tip of the auxiliary implantation carrier, and keeps the combined fiber electrode and the circuit board in the same plane and vertical to the side edge of the circuit board; covering the electrode connection pad with silicon rubber to realize insulation; correspondingly, the fiber nerve electrodes with corresponding numbers are used as electric recording electrodes, are connected with the back of the circuit board in the same way and are adhered to another auxiliary implantation carrier to form a combined fiber recording electrode; the two combined fiber electrodes are kept at a certain distance according to the requirement of the implantation position and are parallel to each other, and the nuclear magnetic compatible nerve electrical stimulation-electrical recording system based on the flexible printed circuit board is prepared.
7. The nuclear magnetic compatible neurostimulation-electrographic system of any of claims 5 or 6, wherein the auxiliary implant carrier comprises an auxiliary implant tungsten filament and an auxiliary implant gelatin fiber;
when the auxiliary implantation carrier is an auxiliary implantation tungsten wire, the preparation process is as follows: arranging two tungsten wires in parallel between electrode contact pads of a circuit board at a certain interval; melting polyethylene glycol at 120-140 ℃, and fixing a tungsten wire on a circuit board by taking the polyethylene glycol as an adhesive, wherein the tungsten wire and the circuit board are kept on the same plane and perpendicular to the side edge of the circuit board;
When the auxiliary implantation carrier is auxiliary implantation gelatin fiber, the preparation process is as follows: mixing gelatin solid with deionized water in a certain volume ratio, heating and dissolving at 100-160 ℃ to obtain a viscous gelatin solution, and rapidly stretching the viscous solution to obtain gelatin fibers immediately before solidification; two gelatin fibers are arranged in parallel between electrode contact pads of a circuit board at a certain interval, and the gelatin fibers and the circuit board are kept on the same plane and perpendicular to the side edges of the circuit board.
8. The nuclear magnetic compatible neuro-electrical stimulation-recording system according to claim 7, wherein it can be applied in the field of brain science.
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