Three-dimensional flexible microelectrode implantation device for assisting hydrogel filling through glass microtubes

Abstract

The invention provides a three-dimensional flexible microelectrode implantation device with a glass microtube assisting in hydrogel filling. The three-dimensional flexible microelectrode implantation device comprises a glass microtube-three-dimensional flexible microelectrode assembly and hydrogel. The forming process of the assembly comprises the steps that a planar flexible microelectrode is prepared, the planar flexible microelectrode comprises a plurality of strip-shaped flexible microelectrodes composed of a substrate layer, a metal layer and a packaging layer, one ends of the strip-shaped flexible microelectrodes are connected in the same plane, the strip-shaped flexible microelectrodes are evenly distributed in the circumferential direction, and micropores are formed in the middles of the strip-shaped flexible microelectrodes; inserting the tips of the glass microtubes into the micropores facing the substrate layer; and folding the flexible microelectrode so that the flexible microelectrode is attached to the glass microtube. After the combination body is implanted into the biological tissue, the hydrogel is filled into the cavity of the microelectrode by virtue of the glass microtube, and the glass microtube is pulled out from the microelectrode while the hydrogel is injected into the glass microtube. According to the invention, the three-dimensional flexible microelectrode is combined with the hydrogel, so that the whole three-dimensional flexible microelectrode is soft enough and has certain mechanical strength, and the problems of large trauma and displacement of recording sites after implantation of a piercing type three-dimensional flexible microelectrode can be effectively solved.

Description

Technical Field

[0001] The invention belongs to the technical field of biomedical engineering neural microelectrode implantation, and in particular relates to a three-dimensional flexible microelectrode implantation device assisted by glass microtubes and filled with hydrogel. Background Art

[0002] Implantable brain-computer interface technology is constantly developing in the recovery and replacement of brain function. Among them, piercing brain electrodes are an extremely important type. In order to reduce the damage of piercing microelectrodes to the brain, rigid electrodes with very small diameters, such as Michigan electrodes, are often used. However, due to the mismatch between the mechanical properties of rigid electrodes and brain tissue, tissue damage and inflammatory reactions will occur, affecting the long-term stable recording of neural signals, which puts higher demands on piercing flexible microelectrodes.

[0003] The piercing flexible microelectrode can reduce the mechanical damage and foreign body reaction of brain tissue by using flexible materials with better biocompatibility. However, the piercing flexible microelectrode requires an overly rigid microneedle to assist in the insertion, and in order to prevent the flexible microelectrode from shifting in the brain after implantation, the microneedle is usually not pulled out after insertion. Since the Young's modulus of the rigid microneedle is 7-8 orders of magnitude higher than that of the brain, the flexible microelectrode still causes some trauma to the brain tissue after implantation. At the same time, most of the current piercing flexible microelectrodes are planar flexible microelectrodes, which only record unidirectional EEG signals and cannot meet the requirements of recording multi-directional stereo EEG signals. These factors will affect the implantation time and recording effect of the piercing flexible microelectrode in the brain tissue. Therefore, the development of a low-traumatic piercing stereo flexible microelectrode implantation device is of great significance for reducing the trauma after the implantation of the piercing flexible microelectrode and recording stable stereo EEG signals.

[0004] After searching the prior art, it was found that David LH et al. of the Howard Hughes Medical Institute in the United States wrote an article in Nature Biomedical Engineering, 2019, 3, 741-753, "Multimodal in vivo brain electrophysiology with integrated glass microelectrodes", in which a flexible microelectrode with three 10×10 micron platinum recording sites was implanted into the CA1 region of the rat hippocampus using a glass pipette to simultaneously obtain multimodal intracellular and extracellular information, electrochemical evaluation, and optogenetic perturbation of neural activity in vivo. However, after the flexible microelectrode was implanted into the rat hippocampus, the glass pipette remained inside the brain, which would result in a rigid glass pipette remaining in the rat brain, resulting in greater implantation trauma.

[0005] Yan D et al. from the Department of Electrical Engineering and Computer Science at the University of Michigan wrote an article titled "Self-Assembled Origami Neural Probes for Scalable, Multifunctional, Three-Dimensional Neural Interface" in bioRxiv, 2024, 591141. First, immerse the manufactured probe in IPA, which has a lower surface tension coefficient than water. After taking it out and drying it completely, transfer the probe to a temporary bracket so that the probe handle stands freely. Then, roughly align and connect an optical fiber to the end of the flexible cable so that the tip of the optical fiber protrudes. Finally, immerse the free-standing probe handle and the tip of the optical fiber in deionized water and slowly pull it out. During this process, the capillary force will completely wrap the sub-handle of the origami probe around the optical fiber. However, during chronic implantation, although the rigid microneedle is pulled out of the brain tissue to prevent the rigid microneedle from staying in the brain for a long time, a cavity will still form inside the flexible microelectrode, and displacement may occur, affecting the stability of the recorded signal.

[0006] CN 111990995 B discloses a flexible electrode implantation system, which uses a foldable flexible electrode and an implantation guide instrument to deliver the flexible electrode into a target brain area. The implantation guide platform and the implantation "triangular prism" guide column enable the foldable flexible electrode to generate a folding angle and maintain the folded state, assisting the foldable flexible electrode to be implanted and then withdrawn and recovered. However, the diameter of the "triangular prism" guide column is larger than the foldable flexible electrode, and a cavity will be formed around the foldable flexible electrode after being pulled out, resulting in increased implantation trauma, and the foldable flexible electrode is prone to displacement during long-term implantation.

[0007] CN 119034104 A discloses a flexible electrode implantation device, including a flexible electrode and a puncture tube. The flexible electrode passes through the puncture tube. After the puncture tube assists the flexible electrode to reach the target position, the puncture tube withdraws from the flexible electrode, and the fixing seat is fixed on the surface of the organism by means of adhesive or binding to complete the stable fixation of the flexible electrode. However, after the puncture tube withdraws from the flexible electrode, a large cavity is formed around the flexible electrode, thereby causing a large implantation trauma, and the cavity easily leads to an unstable recording site position after the flexible electrode is implanted.

[0008] In summary, existing piercing three-dimensional flexible microelectrodes have the problems of large trauma when piercing biological tissues and displacement of the microelectrode recording site when implanted for a long time. Summary of the invention

[0009] In view of the defects and gaps in the prior art, the present invention provides a three-dimensional flexible microelectrode implantation device with glass microtube assisted hydrogel filling, which can effectively reduce the implantation trauma of the piercing flexible microelectrode and at the same time ensure the spatial position stability of the piercing flexible microelectrode during long-term recording of physiological signals.

[0010] To achieve the above purpose, the technical solution provided by the present invention is:

[0011] Provided is a glass microtube-assisted hydrogel-filled three-dimensional flexible microelectrode implantation device, comprising a glass microtube-three-dimensional flexible microelectrode assembly and a hydrogel;

[0012] The glass microtube of the assembly is inserted into and fitted into the three-dimensional flexible microelectrode, and the assembly is used to be implanted into a target biological tissue;

[0013] After the assembly is implanted into the target biological tissue, the hydrogel is filled into the cavity of the three-dimensional flexible microelectrode with the help of a glass microtube to form a soft inner core. The glass microtube is pulled out from the three-dimensional flexible microelectrode while the hydrogel is injected.

[0014] The formation process of the assembly is as follows: prepare a planar flexible microelectrode, which includes a plurality of strip-shaped flexible microelectrodes composed of a substrate layer, a metal layer and a packaging layer, which are connected at one end in the same plane and are evenly distributed in the circumference, and have microholes at the middle connection; the substrate layer facing the planar flexible microelectrode is perpendicular to the plane of the planar flexible microelectrode to insert the tip of the glass microtube into the microhole in the middle of the planar flexible electrode; and each strip-shaped flexible microelectrode is folded to make it fit with the glass microtube.

[0015] Furthermore, a biocompatible coating is filled between the glass microtube and the three-dimensional flexible microelectrode of the assembly.

[0016] Furthermore, the preparation process of the assembly filled with the biocompatible coating is as follows:

[0017] Step 1, heating the solid coating material to melt it into a liquid state;

[0018] Step 2, placing the glass microtube into the liquid coating material and dipping it so that the outside of the glass microtube is covered with the liquid coating material;

[0019] Step 3, naturally cooling the glass microtube wrapped with the liquid coating material to solidify the liquid coating material and complete the three-dimensionalization of the liquid coating material;

[0020] Step 4, placing the planar flexible microelectrode at the tip of the glass microtube after the liquid coating material is three-dimensionalized for assembly;

[0021] Step 5, heating the assembled planar flexible microelectrode and glass microtube to melt the coating material, and folding the planar flexible microelectrode to make it adhere to the glass microtube;

[0022] Step 6, naturally cool the glass microtube with the three-dimensional flexible microelectrode attached to the outside as a whole to solidify the coating material, thereby obtaining a combination of the three-dimensional flexible microelectrode and the glass microtube filled with a biocompatible coating.

[0023] Furthermore, the biocompatible coating is made of one or more materials selected from polyethylene glycol, sodium alginate, polyvinyl alcohol and sucrose.

[0024] Furthermore, the substrate layer and the packaging layer are made of one or both of polyimide and polyparaxylene.

[0025] Furthermore, the hydrogel is made of one or more materials selected from the group consisting of chitosan, alginate and polyethylene glycol.

[0026] Furthermore, the number of the strip-shaped flexible microelectrodes is three or four.

[0027] Furthermore, each strip-shaped flexible microelectrode is provided with six to twenty microelectrode points for recording physiological signals.

[0028] Furthermore, the diameter of the microelectrode point is 50 to 200 microns.

[0029] Furthermore, the glass microtube is manufactured by a needle pulling apparatus.

[0030] The advantages of the present invention are:

[0031] The glass microtube-assisted hydrogel-filled three-dimensional flexible microelectrode implantation device proposed in the present invention can accurately implant the three-dimensional flexible microelectrode into the target biological tissue area through the glass microtube; at the same time, when the glass microtube is pulled out, the hydrogel is filled into the interior of the three-dimensional flexible microelectrode to form a soft inner core, thereby the three-dimensional flexible microelectrode is subjected to a balanced outward force of the hydrogel and an inward force of the biological tissue inside the target biological tissue, so that the three-dimensional flexible microelectrode does not shift in the biological tissue, thereby stably fixing the three-dimensional flexible microelectrode inside the biological tissue through the hydrogel, and the flexible microelectrode filled with hydrogel is soft enough in contact with the surrounding tissue, thereby reducing the trauma to the target biological tissue, and solving the stability and trauma problems of the three-dimensional flexible electrode after implantation into the biological tissue. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] The above and / or other features and advantages of the present invention will become more easily understood through the following description with reference to the accompanying drawings, which are not drawn to scale and some features are exaggerated or reduced to show details of specific components. In the accompanying drawings:

[0033] Figure 1 This is the assembly process of the glass microtube-assisted hydrogel-filled three-dimensional flexible microelectrode implantation device of the present invention;

[0034] Figure 2 It is a schematic diagram of the metal layer structure of the planar flexible microelectrode in the implant device of the present invention;

[0035] Figure 3 It is a schematic diagram of the packaging layer structure of the planar flexible microelectrode in the implant device of the present invention;

[0036] Figure 4 This is a schematic diagram of the process of implanting a three-dimensional flexible microelectrode into biological tissue by glass microtube-assisted hydrogel filling in the present invention;

[0037] Figure 5 It is a process flow chart of the preparation of the glass microtube-three-dimensional flexible microelectrode assembly with added biocompatible coating of the present invention;

[0038] Figure 6 is another schematic diagram of the structure of the planar flexible microelectrode in the implant device of the present invention;

[0039] Figure 7 The present invention utilizes Figure 6 A glass microtube-three-dimensional flexible microelectrode assembly formed by a planar flexible microelectrode.

[0040] In the figure: 1-glass microtube; 2-planar flexible microelectrode; 3-three-dimensional flexible microelectrode; 4-hydrogel; 5-metal layer electrode point area; 6-metal layer wire; 7-metal layer pad; 8-encapsulation layer electrode point opening; 9-encapsulation layer pad opening; 10-biological tissue; 11-solid PEG; 12-liquid PEG; 13-microelectrode group; 14-microelectrode point. DETAILED DESCRIPTION

[0041] The present invention will be described in detail below with reference to the accompanying drawings by means of exemplary embodiments of the present invention. It should be noted that the following detailed description of the present invention is only for the purpose of illustration, and is not intended to limit the present invention.

[0042] The present invention provides a glass microtube-assisted hydrogel-filled three-dimensional flexible microelectrode implantation device, which is used to implant the three-dimensional flexible microelectrode into the target biological tissue. During the implantation process, the three-dimensional flexible microelectrode is accurately implanted through the glass microtube, and when the glass microtube is pulled out, the hydrogel is filled into the three-dimensional flexible microelectrode to form a soft inner core, thereby completing the implantation. The implantation device combines the three-dimensional flexible microelectrode with the hydrogel, which not only makes the three-dimensional flexible microelectrode as a whole sufficiently soft and has a certain mechanical strength, but also has practical value and innovative significance for reducing the trauma after the implantation of the three-dimensional flexible microelectrode, avoiding the displacement of the electrode site due to tissue compression after implantation, and recording three-dimensional multi-directional physiological signals, and can effectively solve the problems of large trauma and displacement of the recording site after the implantation of the piercing three-dimensional flexible microelectrode.

[0043] Reference Figure 1 As an exemplary embodiment of the present invention, a glass microtube-assisted hydrogel-filled three-dimensional flexible microelectrode implantation device includes a glass microtube-three-dimensional flexible microelectrode assembly, and a hydrogel 4. The assembly includes a glass microtube 1 inserted into and attached to a three-dimensional flexible microelectrode 3, and the assembly is used to be implanted into a target biological tissue. The glass microtube 1 has a microchannel in the middle, which can be manufactured by a needle pulling instrument. The diameter and length of the glass microtube 1 are determined by the size of the three-dimensional flexible microelectrode to be implanted. It should be understood that the three-dimensional flexible microelectrode 3 is also tubular corresponding to the glass microtube.

[0044] The formation process of the assembly is as follows: prepare a planar flexible microelectrode 2, the planar flexible microelectrode 2 includes a plurality of strip-shaped flexible microelectrodes composed of a substrate layer, a metal layer and a packaging layer, which are connected at one end in the same plane and are evenly distributed in the circumference, and have micropores at the middle connection; the substrate layer facing the planar flexible microelectrode 2 is perpendicular to the plane of the planar flexible microelectrode 2 to insert the tip of the glass microtube 1 into the micropore in the middle of the planar flexible electrode; fold each strip-shaped flexible microelectrode to make it fit with the glass microtube 1 and attach it to the outer surface of the glass microtube 1, so that the planar flexible microelectrode becomes three-dimensional, and a assembly of the glass microtube 1 and the three-dimensional flexible microelectrode 3 is obtained.

[0045] exist Figure 1In the embodiment shown, the number of the strip-shaped flexible microelectrodes in the planar flexible microelectrode 2 is three, and each strip-shaped flexible microelectrode is provided with a plurality of microelectrode points for recording physiological signals, in particular six to twenty, to form a plurality of microelectrode groups, each microelectrode group including three microelectrode points, and the diameter of the microelectrode points is 50 to 200 microns. However, it will be understood by those skilled in the art that the number of strip-shaped flexible microelectrodes and the number of microelectrode points thereon are not subject to specific restrictions, and various numbers can be set as needed. The substrate layer and the encapsulation layer of the planar flexible microelectrode 2 can be made of one or more materials with low Young's modulus and high flexibility such as polyimide (PI) and polyparaxylene (Parylene).

[0046] The hydrogel 4 is used to fill the cavity containing the glass microtube 1 in the three-dimensional flexible microelectrode 3 with the help of the glass microtube 1 after the combination is implanted into the target biological tissue, so that the inner core of the three-dimensional flexible microelectrode 3 is filled with the hydrogel 4 to form a soft inner core. The glass microtube 1 is pulled out from the three-dimensional flexible microelectrode 3 while injecting the hydrogel 4. Thus, the hydrogel is used as the soft inner core of the electrode to make the three-dimensional flexible microelectrode as a whole sufficiently soft and have a certain mechanical strength, so that the flexible microelectrode is stably fixed inside the biological tissue, which can prevent the three-dimensional flexible microelectrode 3 from shifting in the biological tissue. At the same time, the microelectrode is soft in contact with the tissue, which can avoid large trauma after the flexible microelectrode is implanted in the target biological tissue area. According to the present invention, the hydrogel 4 can be made of one or more materials such as chitosan, alginate and polyethylene glycol, which have a fast dissolution rate and good biocompatibility.

[0047] Reference Figure 2 The exemplary processing flow of the metal layer electrode point area 5, the metal layer wire 6 and the metal layer pad 7 in the middle of the planar flexible microelectrode 2 is as follows:

[0048] First, the silicon wafer was treated with O2 plasma (40w, 2min) before metal sputtering to increase the surface roughness of the PI substrate. Gold (200nm) was deposited on the treated PI substrate by metal magnetron sputtering to obtain an electrode metal layer.

[0049] Secondly, AZ 4620 photoresist was spin-coated on the surface of the metal layer at a speed of 500 rpm for 30 seconds and at a speed of 2500 rpm for 30 seconds, and then placed on a hot plate to bake the photoresist (100°C, 3 minutes) to solidify the photoresist; then, the silicon wafer was placed in a photolithography machine, loaded with a mask and exposed for 7 seconds, and then the silicon wafer was immersed in a developer and continuously shaken to remove the photoresist after UV exposure. After about 1 minute, the silicon wafer was taken out and the developer was cleaned with deionized water to obtain a patterned positive photoresist with a thickness of 5 μm, which was used as a mask for ion beam etching;

[0050] Finally, the metal layer is patterned in an ion beam etching system to obtain the metal layer electrode point area 5 , the metal layer wire 6 and the metal layer pad 7 of the planar flexible microelectrode 2 .

[0051] Reference Figure 3 The exemplary processing flow of the packaging layer electrode point opening 8 and the packaging layer pad opening 9 of the planar flexible microelectrode 2 is as follows:

[0052] First, soak the silicon wafer in acetone for about 90 seconds, then soak it in anhydrous ethanol for about 90 seconds, and then clean it with deionized water; then check it under a microscope, use acetone-soaked absorbent cotton to gently wipe off the unremoved photoresist, and be careful not to damage the three-dimensional flexible microelectrode metal layer, and finally clean it with anhydrous ethanol and deionized water in turn, repeat several times to ensure that the photoresist is completely removed;

[0053] Then, the silicon wafer was treated with O2 plasma again (40w, 1min) to improve the bonding strength between the metal layer and the packaging layer;

[0054] Finally, the negative photosensitive adhesive was spin-coated on the silicon wafer at a speed of 3800 rpm for 30 s, and then pre-baked (90 °C, 100 s), exposed (dose of 400 mJ / cm 2 ), developing (70s in developer, 60s in rinse solution, 30s in mixed solution), and post-baking (300°C, 1h) to obtain a PI packaging layer with a thickness of about 5μm, exposing the packaging layer electrode point openings 8 for collection and stimulation, and the packaging layer pad openings 9 for terminal connection to the FPC cable.

[0055] Reference Figure 4 The process of glass microtube-assisted hydrogel-filled three-dimensional flexible microelectrode implantation into biological tissue is as follows:

[0056] Step (a), under microscope observation, placing the glass microtube 1 and the three-dimensional flexible microelectrode 3 assembly above the target biological tissue 10, inserting the glass microtube-three-dimensional flexible microelectrode assembly into the biological tissue 10 through a micro displacement controller, and strictly controlling the XYZ three-axis movement to implant the assembly into the target biological tissue area, thereby using the rigid glass microtube 1 to accurately implant the soft three-dimensional flexible microelectrode 3 into the target tissue;

[0057] Step (b), after the assembly is implanted into the target biological tissue, the hydrogel 4 is slowly injected into the interior of the three-dimensional flexible microelectrode 3 through the glass microtube 1, and the glass microtube 1 is slowly pulled out while the hydrogel 4 is injected, so that the hydrogel 4 gradually fills the internal cavity of the three-dimensional flexible microelectrode 3. The whole process ensures the stability of the glass microtube 1 and the three-dimensional flexible microelectrode 3 to prevent displacement;

[0058] Step (c), after the hydrogel 4 fills the inner core of the three-dimensional flexible microelectrode 3, the glass microtube 1 is completely pulled out from the target biological tissue 10. At this time, the hydrogel 4 completely fills the internal cavity of the three-dimensional flexible microelectrode 3 to form a soft inner core, and the implantation is completed. After implantation, the three-dimensional flexible microelectrode 3 is subjected to the outward force of the hydrogel 4 and the inward force of the biological tissue 10 in the biological tissue 10, which is balanced, so that the three-dimensional flexible microelectrode 3 will not shift when recording physiological signals in the biological tissue 10 for a long time, and the flexible microelectrode filled with hydrogel is soft enough to contact the surrounding tissue, reducing the trauma to the tissue.

[0059] In a preferred embodiment of the present invention, a biocompatible coating is filled between the glass microtube 1 of the assembly and the three-dimensional flexible microelectrode 3. The biocompatible coating is made of one or more materials selected from materials with fast dissolution speed and good biocompatibility such as PEG (Polyethylene glycol), sodium alginate, polyvinyl alcohol and sucrose.

[0060] Reference Figure 5 , taking PEG as the material of the biocompatible coating as an example, the preparation process of the assembly filled with the biocompatible coating is described:

[0061] Step (a), heating solid PEG 11 to 50-60 degrees Celsius to melt the solid PEG 11 into liquid PEG 12;

[0062] Step (b), placing the glass microtube 1 in liquid PEG 12 for dipping, so that the outside of the glass microtube 1 is coated with the liquid PEG 12;

[0063] Step (c), cooling the glass microtube 1 wrapped with liquid PEG 12 at room temperature to solidify the liquid PEG 12 and complete the three-dimensionalization of the liquid PEG 12;

[0064] Step (d), placing the planar flexible microelectrode 2 on the tip of the three-dimensional glass microtube 1 of liquid PEG 12 for assembly;

[0065] Step (e), heating the assembled planar flexible microelectrode 2 and the glass microtube 1 to 50-60 degrees Celsius to melt the PEG, folding the planar flexible microelectrode 2 to make it adhere to the glass microtube 1, and then the planar flexible microelectrode 2 becomes a three-dimensional flexible microelectrode 3, ensuring that the three-dimensional flexible microelectrode 3 is stably adhered to the surface of the glass microtube 1;

[0066] Step (f), naturally cooling the glass microtube 1 with the three-dimensional flexible microelectrode 3 attached to the outside at room temperature to solidify the PEG, thereby obtaining an implant with a PEG biocompatible coating filled between the three-dimensional flexible microelectrode base layer and the glass microtube.

[0067] Reference Figure 6 and Figure 7 In another embodiment of the present invention, the planar flexible microelectrode 2 with different numbers of microelectrode points is matched according to the size of the target biological tissue, and has 4×6 channels. Specifically, the number of strip-shaped flexible microelectrodes in the planar flexible microelectrode 2 is four, that is, it includes four flexible microelectrode bundles, and each electrode bundle is provided with six microelectrode points. The four microelectrode points in the circumferential direction corresponding to each electrode bundle form a group of microelectrode groups 13. In other words, a group of microelectrode groups 13 includes four microelectrode points 14. By combining the three-dimensional flexible microelectrode with a changed structure with the glass microtube, a three-dimensional flexible microelectrode assembly with a changed structure can be obtained, thereby recording more EEG signals in different directions at the same position of the biological tissue in groups.

[0068] Therefore, as described above, the present invention accurately implants the three-dimensional flexible microelectrode into the target biological tissue area through the glass microtube; at the same time, when the glass microtube is pulled out, hydrogel is filled into the interior of the three-dimensional flexible microelectrode to form a soft inner core, thereby, the three-dimensional flexible microelectrode is subjected to the balance of the outward force of the hydrogel and the inward force of the biological tissue inside the target biological tissue, so that the three-dimensional flexible microelectrode does not shift in the biological tissue, thereby stably fixing the three-dimensional flexible microelectrode inside the biological tissue through the hydrogel, and the flexible microelectrode filled with hydrogel is soft enough in contact with the surrounding tissue, thereby reducing the trauma to the target biological tissue and solving the stability and trauma problems of the three-dimensional flexible electrode after implantation into the biological tissue.

[0069] Finally, it should be noted that the features mentioned and / or shown in the above description of the exemplary embodiments of the present invention may be combined in the same or similar manner into one or more other embodiments, combined with the features in other embodiments or substituted for the corresponding features in other implementations. The technical solutions obtained by these combinations or substitutions shall also be deemed to be included in the protection scope of the present invention.

Claims

1. A three-dimensional flexible microelectrode implantation device assisted by glass microtubes and hydrogel filling, characterized in that: It includes a glass microtube-three-dimensional flexible microelectrode assembly and a hydrogel; The glass microtube of the assembly is inserted into the three-dimensional flexible microelectrode and fits in place, and the assembly is used for implantation into a target biological tissue; The hydrogel is used to be filled into the cavity of the three-dimensional flexible microelectrode containing the glass microtube by means of the glass microtube after the assembly is implanted into the target biological tissue to form a soft inner core, and the glass microtube is pulled out from the three-dimensional flexible microelectrode while injecting the hydrogel; The formation process of the combination is as follows: preparing a planar flexible microelectrode, wherein the planar flexible microelectrode includes a plurality of strip-shaped flexible microelectrodes composed of a substrate layer, a metal layer and a packaging layer, which are connected at one end in the same plane and are evenly distributed in the circumference, and have microholes at the middle connection; inserting the tip of a glass microtube into the microhole in the middle of the planar flexible electrode perpendicularly to the plane of the planar flexible microelectrode with the substrate layer facing the planar flexible microelectrode; and folding each strip-shaped flexible microelectrode to make it fit with the glass microtube.

2. The glass microtube-assisted hydrogel-filled three-dimensional flexible microelectrode implantation device according to claim 1, characterized in that: The glass microtube and the three-dimensional flexible microelectrode of the assembly are filled with a biocompatible coating.

3. The glass microtube-assisted hydrogel-filled three-dimensional flexible microelectrode implantation device according to claim 2, characterized in that: The preparation process of the combination filled with the biocompatible coating is as follows: Step 1, heating the solid coating material to melt it into a liquid state; Step 2, placing the glass microtube into the liquid coating material and dipping it so that the outside of the glass microtube is covered with the liquid coating material; Step 3, naturally cooling the glass microtube wrapped with the liquid coating material to solidify the liquid coating material and complete the three-dimensionalization of the liquid coating material; Step 4, placing the planar flexible microelectrode at the tip of the glass microtube after the liquid coating material is three-dimensionalized for assembly; Step 5, heating the assembled planar flexible microelectrode and glass microtube to melt the coating material, and folding the planar flexible microelectrode to make it adhere to the glass microtube; Step 6, naturally cool the glass microtube with the three-dimensional flexible microelectrode attached to the outside as a whole to solidify the coating material, thereby obtaining a combination of the three-dimensional flexible microelectrode and the glass microtube filled with a biocompatible coating.

4. The glass microtube-assisted hydrogel-filled three-dimensional flexible microelectrode implantation device according to claim 2 or 3, characterized in that: The biocompatible coating is made of one or more materials selected from polyethylene glycol, sodium alginate, polyvinyl alcohol and sucrose.

5. The glass microtube-assisted hydrogel-filled three-dimensional flexible microelectrode implantation device according to claim 1 or 2, characterized in that: The substrate layer and the packaging layer are made of one or both of polyimide and polyparaxylene.

6. The glass microtube-assisted hydrogel-filled three-dimensional flexible microelectrode implantation device according to claim 1 or 2, characterized in that: The hydrogel is made of one or more materials selected from the group consisting of chitosan, alginate and polyethylene glycol.

7. The glass microtube-assisted hydrogel-filled three-dimensional flexible microelectrode implantation device according to claim 1 or 2, characterized in that: The number of the strip-shaped flexible microelectrodes is three or four.

8. The glass microtube-assisted hydrogel-filled three-dimensional flexible microelectrode implantation device according to claim 7, characterized in that: Each strip-shaped flexible microelectrode is provided with six to twenty microelectrode sites for recording physiological signals.

9. The glass microtube-assisted hydrogel-filled three-dimensional flexible microelectrode implantation device according to claim 8, characterized in that: The diameter of the microelectrode point is 50 to 200 microns.

10. The glass microtube-assisted hydrogel-filled three-dimensional flexible microelectrode implantation device according to claim 1 or 2, characterized in that: The glass microtube is manufactured by a needle pulling instrument.

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