CN113521319A - Flexible high-density multifunctional nerve probe for biological implantation and preparation method thereof - Google Patents

Flexible high-density multifunctional nerve probe for biological implantation and preparation method thereof Download PDF

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CN113521319A
CN113521319A CN202110889837.6A CN202110889837A CN113521319A CN 113521319 A CN113521319 A CN 113521319A CN 202110889837 A CN202110889837 A CN 202110889837A CN 113521319 A CN113521319 A CN 113521319A
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polymer
film
nerve probe
polymer material
release layer
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CN113521319B (en
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刘景全
奚野
郭哲俊
王隆春
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Shanghai Jiaotong University
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Abstract

The invention provides a flexible high-density multifunctional nerve probe for biological implantation and a preparation method thereof, wherein the method comprises the following steps: sputtering a release layer; patterning and curing the conductive polymer material; spin-coating and curing the insulating polymer material; after corroding the release layer, cleaning and drying the composite polymer film; winding and attaching a polymer film on the cylindrical surface of a polymer shaft core to prepare a polymer prefabricated blank; drawing the prefabricated blank into filaments by adopting a hot drawing method; and cutting the required polymer composite filament, and grinding and polishing one end face of the polymer composite filament. The flexible nerve probe prepared based on the hot drawing method can realize the multifunctional and multi-channel integration of electrode recording points, liquid channels and optical channels, can freely and flexibly integrate different types, quantities and geometric parameters of the functional channels according to specific application, can realize stimulation or signal acquisition on the same plane or different depths by grinding and polishing at different angles, and has the advantages of simple and convenient preparation process, lower cost and more flexible combination.

Description

Flexible high-density multifunctional nerve probe for biological implantation and preparation method thereof
Technical Field
The invention relates to the technical field of biomedical engineering, in particular to a flexible high-density multifunctional nerve probe for biological implantation and a preparation method thereof.
Background
Implantable nerve probes play an important role in brain science research as the primary means of identifying and manipulating neural behavior, and have great scientific and technical potential. The invention and development of the nerve probe greatly promote the progress of a plurality of fields such as nerve regeneration, brain disease diagnosis, gene editing, tumor immunology, cell manipulation technology and the like.
The currently used nerve probe mainly adopts silicon-based, metal or glass materials, and the Young modulus of the materials is usually 50-500 Gpa, and is different from that of organism soft tissue by more than 2 orders of magnitude. Under the influence of normal physiological activities of organisms such as organism respiration, blood vessel expansion and contraction and the like, the implanted device can continuously generate friction and shearing action with biological tissues of an implanted area, thereby causing and accelerating inflammatory reaction of the implanted area and reducing the recording capacity of the electrode caused by colloid coating. In addition, due to the limitations of material processing methods and capabilities, conventional nerve probes generally have only a single function of electrophysiological signal acquisition, optical stimulation (signal acquisition), and drug delivery. The nerve probe is prepared from a polymer material different from a traditional nerve probe substrate material, so that the overall Young modulus of the device can be effectively reduced, and the biocompatibility of the nerve probe is improved.
Through the search discovery for the prior art:
shifeng Zhou et al, university of southern china, written "Flexible Fiber Probe for effective Neural Stimulation and protection" on Advanced Science, 2020,7, uses polymer materials such as Polycarbonate (PC), polyvinylidene fluoride (PVDF), and Polymethyl methacrylate (PMMA), and realizes a multimodal Fiber optic nerve Probe with high biocompatibility through a hot-drawing process, thereby realizing long-term Stimulation and recording functions with high resolution and high sensitivity.
Polina anikava et al, university of massachusetts, drafted "Multifunctional fibers for multiple tissue optical, electrical and chemical interactions of neural circuits in vivo" on Nature Biotechnology, 2015,33, which used Polycarbonate (PC), Cyclic Olefin Copolymer (COC), Conductive Polyethylene (CPE), and other polymer materials to organize pre-embryos on various polymer material rods and films, then prepared by a hot-drawing process to obtain a flexible nerve probe capable of integrating three functions of electrophysiological signal collection, light stimulation, and drug supply, and successfully applied to long-term in vivo experiments on mice.
In conclusion, the nerve probe prepared based on the polymer material can realize the integration of multiple functions such as electrophysiological signal acquisition, light stimulation, drug supply and the like, and because the nerve probe based on the polymer material has a Young modulus closer to that of biological tissues, the biocompatibility of the nerve probe is obviously improved, and the nerve probe is easier to carry out long-term embedding experiments in vivo. However, the nerve probe made of the existing polymer material has low density of functional pathways, and usually has only several to tens of acquisition/recording functional channels, so a method for preparing a flexible high-density multifunctional nerve probe is urgently needed.
Disclosure of Invention
Aiming at the defects in the prior art, the invention aims to provide a flexible high-density multifunctional nerve probe for biological implantation and a preparation method thereof.
In a first aspect, the present invention provides a method for preparing a flexible high-density multifunctional nerve probe for bioimplantation, comprising the steps of:
s1, depositing a release layer on the substrate for releasing the upper layer structure;
s2, spin-coating a layer of photosensitive thermoplastic conductive polymer material A precursor solution on the release layer to obtain a polymer A film, and patterning the polymer A film to obtain a patterned polymer A film;
s3, after the patterned polymer A film is completely cured, spin-coating a layer of photosensitive thermoplastic insulating polymer material B precursor solution on the patterned polymer A film, and curing to obtain a polymer B film;
s4, removing release layers among the substrate, the polymer A film and the polymer B film, releasing to obtain a composite polymer film formed by the patterned polymer A film and the polymer B film, and cleaning and drying the composite polymer film;
s5, winding the dried composite polymer film of S4 on a prefabricated polymer material shaft core, and winding a plurality of layers along the circumferential direction of the prefabricated polymer material shaft core to obtain a columnar polymer prefabricated blank, and integrating tens to tens of thousands of recording electrodes on the outer layer of the prefabricated polymer material shaft core; an optical path and/or an administration path arranged along the axial direction of the preformed polymer material mandrel;
s6, drawing the polymer preform into a polymer filament by adopting a hot drawing method under preset parameters;
s7, intercepting the polymer filament with a set length, grinding and polishing one end of the intercepted polymer filament, optimizing the surface appearance of each functional passage, forming a horizontal end face or an inclined plane at the end part of the polymer filament so as to realize the stimulation, administration and/or signal acquisition of nerve tissues in the same plane or different depths, and then cleaning and drying to obtain the flexible high-density multifunctional nerve probe for biological implantation.
Preferably, in S1, the material of the release layer is aluminum or chromium;
preferably, the release layer has a thickness of 200nm to 1000 nm.
Preferably, at S2, the precursor solution of the photosensitive thermoplastic conductive polymer material a may be selected from, but not limited to, the following: any one of polyethylene, polypropylene, polystyrene, polymethyl methacrylate or polychloroacetic acid;
the S3, the photosensitive thermoplastic insulating polymer material B precursor solution can be selected from, but not limited to, the following: polycarbonate, polyethylene, polypropylene, polystyrene, polymethyl methacrylate, or polychloroacetic acid.
Optionally, the photosensitive thermoplastic polymer material precursor solutions in S2 and S3 include corresponding monofunctional monomers, photoinitiators, light absorbers, and molecular weight regulators for different thermoplastic polymer materials.
Preferably, in S2, spin-coating a layer of photosensitive thermoplastic conductive polymer material a precursor solution on the release layer to obtain a polymer a film, and patterning the polymer a film to obtain a patterned polymer a film, wherein the photosensitive thermoplastic conductive polymer material a precursor solution is spread on a substrate with a polished surface by using a homomixer, and the rotation speed of the mixer is in a range of 500-3000 rpm; and processing the whole block of polymer A film obtained by spin coating by using an MEMS (micro electro mechanical system) process to form a plurality of small films with solid shapes, thereby obtaining the patterned polymer A film.
Preferably, in step S3, after the patterned polymer a film is completely cured, a layer of precursor solution of photosensitive thermoplastic insulating polymer material B is spin-coated on the patterned polymer a film, wherein the photosensitive thermoplastic insulating polymer material B is spread on the polymer a film by using a homomixer, and the rotation speed of the spinner is in the range of 500-3000 revolutions per minute.
Preferably, the S4 is performed to remove the release layer between the substrate and the polymer a layer, wherein the substrate processed in S3 is immersed in an etching solution to remove the release layer, and the etching solution is applied to the metal material of the release layer selected in S1 to etch the metal material.
Preferably, in S5, the preformed polymer material core is in the form of a solid cylinder, a solid cylinder embedded with a hollow liquid passage, or a cylinder embedded with a solid cylinder.
Preferably, in S6, the polymer preform is drawn into the polymer filament by a hot-drawing method under preset parameters, wherein the heating temperature of the preset parameters is set to be 150 ℃ to 250 ℃.
Preferably, the S7, cutting a set length of the polymer filament, and sanding and polishing one end of the cut polymer filament, wherein a sanding and polishing angle is set to 0 ° to 85 °.
In a second aspect, the present invention provides a flexible high-density multifunctional nerve probe for bioimplantation, which is obtained by using the method for preparing the flexible high-density multifunctional nerve probe for bioimplantation.
Compared with the prior art, the invention has at least one of the following beneficial effects:
according to the method, the composite polymer film is wound on the polymer material shaft core, the photoetching process is combined, the high-density multifunctional flexible electrode is prepared on the basis of the hot drawing method, the multifunctional and multi-channel integration of electrode recording points, liquid channels and optical channels can be realized, the functional channels with different types, numbers and geometric parameters can be freely and flexibly integrated according to specific application, and meanwhile, the stimulation or signal acquisition on the same plane or different depths can be realized through polishing and polishing at different angles. The preparation process is simple and convenient, the cost is lower, and the combination is more flexible.
Drawings
Other features, objects and advantages of the invention will become more apparent upon reading of the detailed description of non-limiting embodiments with reference to the following drawings:
FIG. 1 is a schematic flow chart illustrating the preparation of a flexible high-density multifunctional nerve probe for bioimplantation according to a preferred embodiment of the present invention;
FIG. 2 is a schematic view of a composite polymer film structure according to various alternative patterning schemes in accordance with a preferred embodiment of the present invention;
FIG. 3a is a schematic structural diagram of a composite polymer film according to a preferred embodiment of the present invention;
FIG. 3b is a schematic view of a composite polymeric film wrapped around a cylindrical surface of a mandrel of polymeric material according to a preferred embodiment of the present invention;
FIG. 4a is a schematic structural view of the flexible high-density multifunctional nerve probe for bioimplantation prepared in example 1;
FIG. 4b is a front view of FIG. 4 a;
FIG. 5a is a schematic view of a polymer core structure for use in the fabrication of a flexible high density neuroprobe according to a preferred embodiment of the present invention;
FIG. 5b is a schematic view of the polymer core structure for preparing a flexible high-density optical/electrical integrated nerve probe according to a preferred embodiment of the present invention;
FIG. 5c is a schematic view of the structure of a polymer core for preparing a flexible high-density optical/electrical/drug delivery integrated nerve probe according to a preferred embodiment of the present invention;
FIG. 6a is a schematic diagram of a polymer pre-fabricated embryo structure for use in the fabrication of a flexible high-density optical/electrical integrated neural probe in accordance with a preferred embodiment of the present invention;
FIG. 6b is a schematic diagram of a polymer pre-embryo structure for preparing a flexible high-density optical/electrical/drug delivery integrated neural probe in accordance with a preferred embodiment of the present invention;
FIG. 7 is a schematic view showing a process of preparing a polymer preform into a polymer filament by a hot-drawing method according to a preferred embodiment of the present invention;
FIG. 8 is a schematic view of a process for preparing a flexible high-density multifunctional integrated neural probe by cutting a portion of a polymer filament according to a preferred embodiment of the present invention;
FIG. 9a is a schematic illustration of the end portion of the polymer filament of example 1 forming a horizontal end face;
FIG. 9b is a schematic representation of the end-beveling of the polymer filament of example 2;
FIG. 9c is a schematic representation of the end-beveling of the polymer filament of example 3;
FIGS. 10a and 10b are schematic views of the polishing surface of the flexible high-density multifunctional nerve probe after polishing at different angles according to the present invention;
the scores in the figure are indicated as: 1 is a composite polymer film, 2 is a polymer material shaft core, 11 is a functional passage, 21 is an optical passage, and 22 is an administration passage.
Detailed Description
The present invention will be described in detail with reference to specific examples. The following examples will assist those skilled in the art in further understanding the invention, but are not intended to limit the invention in any way. It should be noted that variations and modifications can be made by persons skilled in the art without departing from the spirit of the invention. All falling within the scope of the present invention.
Example 1
The present embodiment provides a method for preparing a flexible high-density multifunctional nerve probe for bioimplantation, as shown in fig. 1, according to the following steps:
s1, sputtering a layer of aluminum on the substrate as a release layer for releasing the polymer film layer, wherein the substrate can be a silicon wafer with a polished surface or a glass wafer, as shown in fig. 1 (b); the material of the release layer can be chromium besides aluminum; the thickness of the sputter release layer can be selected from, but is not limited to, 200nm to 1000 nm.
S2, a layer of conductive polyethylene precursor liquid is spin-coated on the release layer to obtain a polymer A film, the polymer A film is patterned to obtain a patterned polymer A film, and different geometric shapes and parameters of the patterned polymer A film can be designed according to actual requirements. Refer to fig. 1 (c); the precursor solution of the photosensitive thermoplastic conductive polymer material A can be selected from polyethylene, polypropylene, polystyrene, polymethyl methacrylate, polychloroacetic acid and other polymer materials.
S3, after the conductive polyethylene precursor liquid is completely cured, spin-coating a layer of polycarbonate precursor liquid on the conductive polyethylene precursor liquid, and curing to obtain a polymer B film, as shown in (d) of fig. 1; the precursor solution of the photosensitive thermoplastic insulating polymer material B can also adopt polymer materials such as polyethylene, polypropylene, polystyrene, polymethyl methacrylate, polyvinyl chloride acetic acid and the like.
And S4, soaking the substrate in corrosive liquid to remove release layers among the substrate, the polymer A film and the polymer B film, releasing to obtain a composite polymer film 1 formed by the polymer A film and the polymer B film, washing the composite polymer film 1 by using deionized water, acetone, absolute ethyl alcohol and deionized water in sequence, and drying. The corrosive liquid is suitable for the metal material of the release layer selected in the S1, the metal material of the release layer of the S1 is aluminum, and the corrosive liquid is dilute hydrochloric acid for corroding the metal aluminum release layer. For example, when the metal material of the release layer of S1 is chromium, the etching solution is a chromium etching solution.
S5, referring to fig. 5a, a polymeric material core 2 of a solid cylindrical structure is prefabricated. Referring to fig. 3a and 3b, the composite polymer film 1 cleaned and dried in S4 is wound and attached on the cylindrical surface of the prefabricated polymer material core 2, and is wound in multiple layers along the circumferential direction of the prefabricated polymer material core 2 as required, so as to realize integration of tens to tens of thousands of functional pathways 11 (recording electrodes), and obtain a cylindrical polymer preform. The preformed polymeric material core is provided with optical waveguides distributed in the axial direction and/or said preformed polymeric material core is provided with optical waveguides distributed in the axial direction and/or the administration channel 22.
The function of the functional channel 11 is to prepare different functional channels during the later drawing, such as electrical stimulation/collection or drug delivery functions. The administration channel is disposed on the core of the polymeric material.
S6, drawing the polymer preform into a filament by a hot drawing method under preset parameters, as shown in FIG. 7; the hot-drawing method mainly comprises parameter settings of heating temperature and drawing speed in preset parameters, wherein the heating temperature is related to the composite polymer material and is generally set to be between 150 and 250 ℃ but not limited to.
S7, referring to fig. 8, intercepting a polymer filament of a certain length, and polishing one end of the polymer filament, wherein the polishing angle is 0 ° as shown in fig. 9 (a), so that the end of the polymer filament forms a horizontal end face, and the polymer filament is sequentially washed with deionized water, acetone, absolute ethyl alcohol, and deionized water, and dried, referring to fig. 4a and 4b, to obtain a flexible high-density multifunctional nerve probe for bioimplantation, which can be used for signal acquisition and stimulation in the same brain region plane.
The composite polymer film 1 in S2 and S3 may be, but is not limited to, a precursor solution of the photosensitive thermoplastic conductive polymer material a and a precursor solution of the photosensitive thermoplastic insulating polymer material B, and the composite polymer film 1 to be patterned is prepared. Referring to FIG. 2, the composite polymer film may be selected from a combination of different patterning schemes.
Example 2
The present embodiment provides a method for preparing a flexible high-density multifunctional nerve probe for bioimplantation, comprising the steps of:
s1, sputtering an aluminum release layer on the substrate for subsequent release of the polymer film layer, as shown in fig. 1 (b).
S2, a layer of the precursor solution mixed with the graphite conductive polyethylene is spin-coated on the release layer to obtain a polymer a film, and the polymer a film is patterned to obtain a patterned polymer a film, as shown in fig. 1 (c).
S3, after the graphite conductive polyethylene precursor solution is completely solidified, spin-coating a layer of cyclic olefin copolymer precursor solution on the graphite conductive polyethylene precursor solution, and solidifying to obtain a polymer B film, as shown in fig. 1 (d).
And S4, soaking the substrate in corrosive liquid to remove the release layer between the substrate and the polymer A film and the polymer B film, releasing to obtain a composite polymer film formed by the polymer A film and the polymer B film, washing the released composite polymer film by using deionized water, acetone, absolute ethyl alcohol and deionized water in sequence, and drying.
S5, referring to fig. 5b, which is a schematic structural view of the prefabricated optical via 21-integrated polymer material core 2; and (3) winding and attaching the cleaned and dried composite polymer film on the cylindrical surface of the polymer material shaft core 2 integrated with the optical path 21 to prepare a polymer prefabricated blank, and referring to fig. 6 a.
S6, drawing the polymer preform into a filament by a hot-drawing method under predetermined parameters, as shown in fig. 7.
S7, referring to the figure 8, intercepting the polymer filament with the set length, referring to the figure 9b, grinding and polishing one end of the polymer filament at a certain angle to enable the end face of the polymer filament to be an inclined plane, sequentially cleaning the polymer filament by using deionized water, acetone, absolute ethyl alcohol and deionized water, and drying to obtain the flexible high-density multifunctional nerve probe for biological implantation, wherein the probe can be used for stimulation and signal acquisition of nerve tissues in different brain region depths.
Example 3
The present embodiment provides a method for preparing a flexible high-density multifunctional nerve probe for bioimplantation, comprising the steps of:
s1, sputtering an aluminum release layer on the substrate for subsequent release of the polymer film layer, as shown in fig. 1 (b).
S2, a layer of the precursor solution mixed with the graphite conductive polyethylene is spin-coated on the release layer to obtain a polymer a film, and the polymer a film is patterned to obtain a patterned polymer a film, as shown in fig. 1 (c).
And S3, after the graphite-mixed conductive polyethylene is completely cured, spin-coating a layer of cycloolefin copolymer precursor solution on the graphite-mixed conductive polyethylene, and curing to obtain a polymer B film, as shown in (d) in FIG. 1.
And S4, soaking the substrate in corrosive liquid to remove the release layer between the substrate and the polymer A film and the polymer B film, releasing to obtain a composite polymer film formed by the polymer A film and the polymer B film, washing the released composite polymer film by using deionized water, acetone, absolute ethyl alcohol and deionized water in sequence, and drying.
S5, referring to fig. 5c, the preformed polymer material core 2 is provided with an optical path formed by the optical waveguide polymer and a drug delivery path for liquid flow formed by a hollow channel along the axial direction, and the optical path is parallel to the drug delivery path. And (3) winding and attaching the cleaned and dried composite polymer film on the cylindrical surface of the prefabricated polymer material shaft core 2 to prepare a polymer prefabricated blank, and referring to fig. 6 b.
S6, drawing the polymer preform into a filament by a hot-drawing method under predetermined parameters, as shown in fig. 7.
S7, referring to fig. 8, cutting a polymer filament with a predetermined length, polishing one end of the polymer filament to make the end surface of the polymer filament an inclined surface, cleaning the polymer filament with deionized water, acetone, absolute ethyl alcohol, and deionized water, and drying the polymer filament.
In the above S7, different angles may be adopted for polishing, which is used for optimizing the surface topography of each functional pathway 11, and the polishing angle may be set to 0 ° -85 ° but not limited thereto, and is used for realizing stimulation, drug delivery and signal acquisition of nerve tissues in the same plane or different depths; referring to fig. 10a and 10b, schematic diagrams of the polishing surface of the flexible high-density multifunctional nerve probe when the grinding and polishing angle is greater than 0 °.
According to the embodiment, the flexible nerve probe prepared based on the hot drawing method can realize the multifunctional and multi-channel integration of the electrode recording points, the liquid channels and the optical paths, can freely and flexibly integrate the functional channels with different types, quantities and geometric parameters according to specific application, and can realize the stimulation or signal acquisition on the same plane or different depths by grinding and polishing at different angles. The method has the advantages of simple and convenient preparation process, low cost and more flexible combination.
The foregoing description of specific embodiments of the present invention has been presented. It is to be understood that the present invention is not limited to the specific embodiments described above, and that various changes or modifications may be made by one skilled in the art within the scope of the appended claims without departing from the spirit of the invention.

Claims (10)

1. A method of making a flexible, high-density multifunctional nerve probe for bioimplantation, comprising:
s1, depositing a release layer on the substrate for releasing the upper layer structure;
s2, spin-coating a layer of photosensitive thermoplastic conductive polymer material A precursor solution on the release layer to obtain a polymer A film, and patterning the polymer A film to obtain a patterned polymer A film;
s3, after the patterned polymer A film is completely cured, spin-coating a layer of photosensitive thermoplastic insulating polymer material B precursor solution on the patterned polymer A film, and curing to obtain a polymer B film;
s4, removing release layers among the substrate, the polymer A film and the polymer B film, releasing to obtain a composite polymer film formed by the patterned polymer A film and the polymer B film, and cleaning and drying the composite polymer film;
s5, winding the dried composite polymer film of S4 on a prefabricated polymer material shaft core, and winding a plurality of layers along the circumferential direction of the prefabricated polymer material shaft core to obtain a columnar polymer prefabricated blank, and integrating tens to tens of thousands of recording electrodes on the outer layer of the prefabricated polymer material shaft core; an optical path and/or an administration path arranged along the axial direction of the preformed polymer material mandrel;
s6, drawing the polymer preform into a polymer filament by adopting a hot drawing method under preset parameters;
s7, intercepting the polymer filament with a set length, grinding and polishing one end of the intercepted polymer filament, optimizing the surface appearance of each functional passage, forming a horizontal end face or an inclined plane at the end part of the polymer filament so as to realize the stimulation, administration and/or signal acquisition of nerve tissues in the same plane or different depths, and then cleaning and drying to obtain the flexible high-density multifunctional nerve probe for biological implantation.
2. The method for preparing a flexible high-density multifunctional nerve probe for bioimplantation as claimed in claim 1, wherein in S1, the material of the release layer is selected from aluminum or chromium;
the thickness of the release layer is 200nm-1000 nm.
3. The method for preparing a flexible high-density multifunctional nerve probe for bioimplantation as claimed in claim 1, wherein said S2 precursor solution of photosensitive thermoplastic conductive polymer material a is selected from any one of polymer materials of polyethylene, polypropylene, polystyrene, polymethyl methacrylate or polychloroacetic acid;
and S3, selecting any one polymer material of polycarbonate, polyethylene, polypropylene, polystyrene, polymethyl methacrylate or polychloroacetic acid as the precursor liquid of the photosensitive thermoplastic insulating polymer material B.
4. The method according to claim 1, wherein in step S2, a layer of precursor solution of photosensitive thermoplastic conductive polymer material a is spin-coated on the release layer to obtain a polymer a film, and the polymer a film is patterned to obtain a patterned polymer a film, wherein the precursor solution of photosensitive thermoplastic conductive polymer material a is spread on a surface-polished substrate by a homomixer, and the rotation speed of the spinner is in the range of 500-3000 rpm; and processing the whole block of polymer A film obtained by spin coating by using an MEMS (micro electro mechanical system) process to form a plurality of small films with solid shapes, thereby obtaining the patterned polymer A film.
5. The method as claimed in claim 1, wherein the step S3 of preparing the flexible high-density multifunctional nerve probe for bioimplantation comprises, after the patterned polymer a film is completely cured, spin-coating a precursor solution of photosensitive thermoplastic insulating polymer material B on the patterned polymer a film, wherein the photosensitive thermoplastic insulating polymer material B is spread on the polymer a film by a homomixer, and the rotation speed of the spinner is in the range of 500-3000 rpm.
6. The method of claim 1, wherein the step S4 is performed to remove the release layer between the substrate and the polymer A layer, wherein the substrate subjected to the step S3 is immersed in an etching solution to remove the release layer, and the etching solution is applied to the metal material of the release layer selected in the step S1 to etch the metal material.
7. The method of claim 1, wherein the preformed polymer material core is formed in any one of a solid cylindrical structure, a solid cylindrical structure having an optical waveguide embedded therein, and a cylindrical structure having a hollow fluid passage embedded therein, in S5.
8. The method for preparing a flexible high-density multifunctional nerve probe for bioimplantation as claimed in claim 1, wherein the S6 is prepared by drawing the polymer preform into polymer filament using hot drawing method under preset parameters, wherein the heating temperature of the preset parameters is set at 150-250 ℃.
9. The method of preparing a flexible high-density multifunctional nerve probe for bioimplantation as claimed in claim 1, wherein the S7 cutting a set length of the polymer filament and grinding and polishing one end of the cut polymer filament, wherein the grinding and polishing angle is set to 0 ° to 85 °.
10. A flexible high-density multifunctional nerve probe for bioimplantation, which is obtained by the method for preparing the flexible high-density multifunctional nerve probe for bioimplantation according to any one of claims 1 to 9.
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