WO2023186053A1 - 柔性神经电极复合结构及制造、植入方法和辅助植入组件 - Google Patents

柔性神经电极复合结构及制造、植入方法和辅助植入组件 Download PDF

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Publication number
WO2023186053A1
WO2023186053A1 PCT/CN2023/085296 CN2023085296W WO2023186053A1 WO 2023186053 A1 WO2023186053 A1 WO 2023186053A1 CN 2023085296 W CN2023085296 W CN 2023085296W WO 2023186053 A1 WO2023186053 A1 WO 2023186053A1
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Prior art keywords
auxiliary
implant
flexible neural
flexible
auxiliary implant
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PCT/CN2023/085296
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English (en)
French (fr)
Inventor
方英
田慧慧
方润九
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北京智冉医疗科技有限公司
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Publication of WO2023186053A1 publication Critical patent/WO2023186053A1/zh

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
    • A61B5/25—Bioelectric electrodes therefor
    • A61B5/279—Bioelectric electrodes therefor specially adapted for particular uses
    • A61B5/291—Bioelectric electrodes therefor specially adapted for particular uses for electroencephalography [EEG]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
    • A61B5/25—Bioelectric electrodes therefor
    • A61B5/279—Bioelectric electrodes therefor specially adapted for particular uses
    • A61B5/291—Bioelectric electrodes therefor specially adapted for particular uses for electroencephalography [EEG]
    • A61B5/293—Invasive
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
    • A61B5/316—Modalities, i.e. specific diagnostic methods
    • A61B5/369—Electroencephalography [EEG]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode

Definitions

  • the present disclosure relates to the technical field of neuroscience, and in particular to a flexible neural electrode composite structure, its manufacturing method and implantation method, composite structural components and its implantation method, and auxiliary implantation components.
  • implantable neural electrodes have developed rapidly as an important tool for brain function analysis, brain disease treatment and brain-computer interface.
  • traditional implantable neural electrodes are rigid and do not match the mechanical properties of brain tissue, after they are implanted in the brain, they will move with each other under the influence of breathing and movement, thus causing damage to the electrodes.
  • the surrounding brain tissue will cause greater damage, which in turn triggers an inflammatory response.
  • immune proliferating cells wrap around the electrode surface, the brain electrode recording signal will continue to weaken until it becomes ineffective.
  • flexible neural electrodes Compared with rigid neural electrodes, flexible neural electrodes have mechanical properties that are more consistent with neural tissue, can reduce immune damage to brain tissue, thereby improving the stability of neural signal detection, and can be used for long-term recording of brain electrical signals.
  • flexible neural electrodes Compared with rigid neural electrodes, flexible neural electrodes have mechanical properties that are more consistent with neural tissue, can reduce immune damage to brain tissue, thereby improving the stability of neural signal detection, and can be used for long-term recording of brain electrical signals.
  • how to achieve high-throughput and large-scale implantation of flexible neural electrodes in the brain (and other neural tissues) is an urgent problem that needs to be solved.
  • Embodiments of the present disclosure provide a flexible neural electrode composite structure, a manufacturing method and an implantation method thereof, a composite structural component and an implantation method thereof, and an auxiliary implantation component.
  • a flexible neural electrode composite structure including: a plurality of flexible neural electrodes, each of the flexible neural electrodes including an implanted portion and an implanted portion disposed on the implanted portion.
  • Auxiliary structure including a plurality of auxiliary implant needles corresponding to the plurality of flexible nerve electrodes, each of the auxiliary implant needles including an auxiliary implant located close to one end of the corresponding flexible nerve electrode end, the auxiliary implant end is configured to be assembled with the auxiliary structure; and a fixer is configured to fix the assembled auxiliary implant end and the auxiliary structure.
  • a method for manufacturing a flexible neural electrode composite structure including: providing a plurality of flexible neural electrodes, each of the flexible neural electrodes including an implanted portion and an auxiliary electrode formed on the implanted portion. Structure; forming an auxiliary implant assembly, the auxiliary implant assembly including a plurality of auxiliary implant needles, each of the auxiliary implant needles including an auxiliary implant end located close to the side of the plurality of flexible nerve electrodes; assembling the The auxiliary implant end and the auxiliary structure; and the fixedly assembled auxiliary implant end and the auxiliary structure.
  • a method for implanting a flexible neural electrode using the aforementioned flexible neural electrode composite structure including: moving the flexible neural electrode composite structure to drive the implantation of the plurality of flexible neural electrodes. Move the part to the surface of the target tissue; melt or dissolve the fixation so that the auxiliary implant end and the auxiliary structure are in a detachable state; move the auxiliary implant component toward the target tissue to drive all moving the plurality of implanted portions of the plurality of flexible neural electrodes to the target tissue; and removing the auxiliary implant assembly and leaving the plurality of flexible neural electrodes at the target tissue.
  • a composite structural assembly including the aforementioned flexible neural electrode composite structure.
  • a method for implanting flexible neural electrodes using the aforementioned composite structure assembly including: using the plurality of flexible neural electrode composite structures to implant multiple groups of flexible neural electrodes into target tissues, each The set of flexible neural electrodes includes a plurality of flexible neural electrodes.
  • an auxiliary implant assembly including: an auxiliary fixation component, the auxiliary fixation component including at least one auxiliary fixation plate; a plurality of auxiliary implant needles configured to connect with the at least one auxiliary fixation plate. Connection, the extension direction of the plurality of auxiliary implant needles is not parallel to the plane where the at least one auxiliary fixation plate is located.
  • Figure 1 is a three-dimensional schematic diagram of a flexible neural electrode composite structure provided by an embodiment of the present disclosure.
  • Figure 2 is a schematic cross-sectional view of the flexible neural electrode composite structure of Figure 1 taken along the dotted plane a.
  • Figure 3 is a partially enlarged schematic diagram of the flexible neural electrode composite structure in Figure 2.
  • FIG. 4A is a partial three-dimensional structural diagram of region b of the flexible neural electrode composite structure in FIG. 1 .
  • FIG. 4B is a top view of the flexible neural electrode array of FIG. 1 .
  • Figure 5 is a schematic structural diagram of an auxiliary implant component provided by an embodiment of the present disclosure.
  • Figure 6 is a schematic cross-sectional view of an auxiliary implant component according to another embodiment of the present disclosure.
  • Figure 7 is a schematic structural diagram of a flexible neural electrode composite structure provided by another embodiment of the present disclosure.
  • Figure 8 is a flow chart of a method for manufacturing a flexible neural electrode composite structure provided by an embodiment of the present disclosure.
  • Figure 9 is a schematic structural diagram of a flexible neural electrode formed in the manufacturing method of a flexible neural electrode composite structure provided by an embodiment of the present disclosure.
  • FIG. 10 is a schematic cross-sectional view taken along line AA in FIG. 9 .
  • 11 to 13 are schematic cross-sectional views of a method for manufacturing an auxiliary implant component according to an embodiment of the present disclosure.
  • Figure 14 is a schematic structural diagram of a composite structural component provided by an embodiment of the present disclosure.
  • Figure 15 is a method for implanting a flexible neural electrode using the flexible neural electrode composite structure of Figure 1 provided by an embodiment of the present disclosure.
  • embodiments of the present disclosure provide a flexible neural electrode composite structure, a manufacturing method and an implantation method thereof, a composite structure component and an implantation method thereof, and an auxiliary implantation component.
  • a flexible neural electrode with an auxiliary implantation component The composite structure enables high-throughput implantation, reduces implantation difficulty, and shortens operation time.
  • At least one embodiment of the present disclosure provides a flexible neural electrode composite structure, including: a plurality of flexible neural electrodes, each flexible neural electrode including an implant part and an auxiliary structure disposed on the implant part; an auxiliary implant component including a plurality of A plurality of auxiliary implant needles corresponding to one flexible nerve electrode, each auxiliary implant needle including an auxiliary implant end located close to one end of the corresponding flexible nerve electrode, and the auxiliary implant end is configured to be assembled with the auxiliary structure; and a fixture configured to secure the assembled auxiliary implant end and auxiliary structure.
  • the auxiliary implant end and the auxiliary structure are fixed with a fixation, thereby fixing the auxiliary implant component and the multiple flexible neural electrodes together, so that during the flexible neural electrode implantation process , multiple flexible neural electrodes can be implanted into target tissues at the same time.
  • the implantation time is shortened and the difficulty of implantation is reduced, thereby achieving the implantation of high-throughput and high-coverage flexible neural electrode arrays; on the other hand, in the implantation of flexible Before the nerve electrode is installed, the assembled flexible nerve electrode and the auxiliary implant component are fixed or connected together with a fixation, which eliminates the need to assemble the flexible nerve electrode and the auxiliary implant component together on site during implantation, and improves the efficiency of the nerve electrode.
  • the implantation efficiency is improved and the operation time is shortened; in addition, because the flexible neural electrode and auxiliary implant components are assembled into a whole structure, they are easy to transport and use.
  • "multiple" Refers to two or more.
  • multiple flexible neural electrodes can be arranged in one row or multiple rows, thereby forming a flexible neural electrode array.
  • Multiple auxiliary implant needles can also be arranged in one or more rows to form an auxiliary implant needle array.
  • the auxiliary implanted needle array is an array of optical fibers, tungsten wires, platinum-iridium alloy wires, and nickel-chromium alloy wires arranged in three-dimensional space; or a silicon needle array prepared by micro-electro-mechanical system (MEMS). ; Or a comb-shaped array obtained by deep silicon etching; or a needle-shaped array obtained by MEMS processing.
  • MEMS micro-electro-mechanical system
  • Figure 1 is a three-dimensional schematic diagram of a flexible neural electrode composite structure provided by an embodiment of the present disclosure.
  • a flexible neural electrode composite structure 100 includes a plurality of flexible neural electrodes 1 (ie, flexible neural electrode arrays), an auxiliary implant component 2 and a fixation 3 .
  • each flexible neural electrode 1 includes an implant portion 10 and an auxiliary structure 11 provided on the implant portion 10 .
  • the implantation part 10 is configured to be implanted into a target tissue, such as human or animal brain tissue, under the action of external force.
  • Figure 2 is a schematic cross-sectional view of the flexible neural electrode composite structure of Figure 1 taken along the dotted plane a.
  • Figure 3 is a partially enlarged schematic diagram of the flexible neural electrode composite structure in Figure 2.
  • the implanted portion 10 of the flexible neural electrode 1 includes, for example, a flexible insulating layer 101 and at least one conductive layer 102 embedded in the flexible insulating layer 101 .
  • the conductive layer 102 includes a plurality of conductive lines 103 .
  • the plurality of conductive lines 103 are insulated from each other by the flexible insulating layer 101 .
  • a plurality of electrode sites 104 are provided on the implanted part 10 , and the plurality of electrode sites 104 are connected to a plurality of conductive wires 103 in one-to-one correspondence for nerve recording or regulation.
  • electrode sites 104 are formed by removing portions of flexible insulating layer 101 to expose conductive lines 103 .
  • each implanted part 10 in FIG. 3 and FIG. 4A only shows 10 electrode sites 104 and 10 conductive lines 103 connected thereto. It can be understood that in other embodiments of the present disclosure, each implanted part 10 The number of electrode sites 104 and the number of conductive lines 103 can be determined according to actual needs. The embodiment does not limit this.
  • the plurality of implant parts 10 of the plurality of flexible neural electrodes 1 may be arranged in various ways.
  • FIG. 4B is a top view of the plurality of flexible neural electrodes of FIG. 1 .
  • multiple implant parts 10 are arranged in a 4 ⁇ 3 array.
  • the multiple implant structures 10 can also be arranged in m rows and n columns, where m is greater than or equal to 1. , n is greater than or equal to 1.
  • each coiled structure is approximately 1 mm.
  • the width of each flexible neural electrode is approximately 15 ⁇ m, and each flexible neural electrode has 10 detection sites (i.e., electrode sites 104).
  • the implanted part is divided into a five-layer structure (insulating layer/conductive layer/insulating layer/ conductive layer/insulating layer).
  • the overall thickness of the flexible neural electrode is approximately 2.5 ⁇ m.
  • the implanted part 10 is located at the front end of each flexible nerve electrode 1, and the rear end of each flexible nerve electrode 1 is provided with a soldering pad corresponding to each electrode site 104, and the soldering pad is connected to an external circuit.
  • the implant portion 10 is provided with an auxiliary structure 11 configured to be connected with the auxiliary implant component 2 .
  • the auxiliary structure 11 and the auxiliary implant component 2 are connected to each other through plugging.
  • the auxiliary implantation component 2 includes, for example, a plurality of auxiliary implantation needles 20 corresponding to a plurality of flexible nerve electrodes 1.
  • Each auxiliary implantation needle 20 includes an auxiliary implantation end 201 and a fixed end 202.
  • the auxiliary implantation end 201 is located at one end of the auxiliary implantation needle 20 close to the flexible nerve electrode 1
  • the fixed end 202 is located at the other end of the auxiliary implantation needle 20 away from the flexible nerve electrode 1 .
  • the auxiliary implant end 201 is configured to be assembled with the auxiliary structure 11, so that the flexible neural electrode 1 and the auxiliary implant component 2 can be assembled together.
  • connection between multiple flexible neural electrodes 1 and the auxiliary implant component 2 is realized by using the assembled auxiliary implant end 201 and the auxiliary structure 11, which is conducive to batch implantation of multiple flexible neural electrodes 1 through the auxiliary implant component 2.
  • the extension direction of the plurality of auxiliary implant needles 20 is not parallel to the extension direction of the plurality of implant portions 10 of the plurality of flexible neural electrodes 1 .
  • the extension directions of the plurality of auxiliary implant needles 20 and the extension directions of the plurality of implant portions 10 of the plurality of flexible neural electrodes 1 intersect in space, that is, they may or may not intersect.
  • a plurality of auxiliary implant needles 20 are parallel to each other and extend along the z direction.
  • the implanted part 10 of each flexible neural electrode 1 is, for example, a stretchable spiral structure, and the plane where the spiral structure is located is the xy plane.
  • the extension direction z of the auxiliary implant needle 20 is different from the xy plane where the spiral structure is located. Parallel, e.g. perpendicular to each other.
  • the flexible nerve electrode when the flexible nerve electrode is implanted, by making the extension direction of the plurality of auxiliary implantation needles 20 and the extension direction of the plurality of implant portions 10 of the plurality of flexible nerve electrodes 1 perpendicular to each other, it is beneficial to control the implantation of the flexible nerve electrode. penetration depth, allowing the flexible neural electrode to reach the target tissue.
  • the auxiliary implant needle 20 can have a certain tilt angle relative to the xy plane where the spiral structure is located.
  • the tilt angle is, for example, greater than 0 degrees and less than or equal to 90 degrees. This is also beneficial to controlling the implantation depth of the flexible neural electrode. Therefore, the embodiment of the present disclosure is suitable for This is not limited.
  • each flexible neural electrode 1 when the implanted part 10 of each flexible neural electrode 1 is a stretchable spiral structure, it is beneficial to use the auxiliary implant component 2 to implant the flexible neural electrode 1 during the implantation process.
  • the spiral structure unfolds to flexibly adjust the implantation depth of the flexible neural electrode 1, further reducing the difficulty of implantation.
  • the spiral structure when the thickness of the spiral structure in the z direction is ignored, can be a two-dimensional planar structure as shown in Figure 1, or a three-dimensional three-dimensional structure, that is, it spirals in the z-direction into a three-dimensional shape. There are no public restrictions on this. Further, when the spiral structure is a two-dimensional planar structure as shown in Figure 1, the spiral structure has, for example, a circle, a triangle, a quadrilateral, a polygon or a rounded triangle, a rounded quadrilateral, a rounded polygon, etc. Preferably, the spiral structure It has a circular shape, which can be formed into a semicircle (i.e.
  • the auxiliary structure 11 is located at the end of the spiral structure, that is, the end of the implantation part 10 , which facilitates easier traction or pulling of the spiral structure to unfold during the implantation process of the flexible neural electrode. It can be understood that in other embodiments of the present disclosure, the auxiliary structure 11 may also be located at other positions at the end of the implant part 10 (for example, the C1 position between the two electrode sites 104 in FIG. 4A), or at the implant site. The part of the insertion part 10 far away from the end (for example, the C2 position in FIG. 4A) can also extend or unfold the flexible nerve electrode. Therefore, the embodiment of the present disclosure does not limit the position of the auxiliary structure 11.
  • FIGS. 1 and 2 only show that the implant part 10 is a stretchable spiral structure. It can be understood that in other embodiments of the present disclosure, the implant part 10 can also have other shapes, such as a linear structure or Wave structure, etc.
  • the implant portion 10 may be one or more of a spiral structure, a wavy structure, and a linear structure.
  • auxiliary implant end 201 and the auxiliary structure 11 are detachably assembled together, for example, by plugging, which facilitates installation and disassembly.
  • the auxiliary implant end 201 and the auxiliary structure 11 are assembled together by plugging.
  • the auxiliary structure 11 is, for example, a through hole 111 located on the implant part 10 .
  • the auxiliary implant end 201 includes a tip 203 , the diameter of which is smaller than or equal to the diameter of the auxiliary implant needle 20 .
  • the tip 203 has a cross-section that gradually decreases toward the auxiliary structure 11 , such as a cone shape as shown in the figure, and the cone shape may be a cone or a pyramid. In this way, when assembling the auxiliary implant end 201 and the auxiliary structure 11, the tip 203 can play a guiding role, which facilitates rapid insertion of the auxiliary structure 11 for assembly.
  • the tip 203 may also have a flat head, and the embodiment of the disclosure does not specifically limit the shape of the tip 203 .
  • FIG. 4A only shows the case where the auxiliary structure 11 is a through hole.
  • the auxiliary structure 11 can also be a groove or a protrusion. As long as it can be plugged into the auxiliary implant end 201, it can be used. included in the embodiments of the present disclosure.
  • part or all of the auxiliary implant end 201 is inserted into the auxiliary structure 11 .
  • the auxiliary implant end 201 when the auxiliary implant end 201 is fully inserted into the auxiliary structure 11, the firmness after assembly can be improved; when the auxiliary implant end 201 is partially inserted into the auxiliary structure 11, it is convenient to insert the flexible neural electrode 1 after implantation.
  • the flexible neural electrode 1 and the auxiliary implant component 2 are separated.
  • the auxiliary implant end 201 is partially inserted into the through hole 111 , that is, the tip 203 is inserted into the through hole 111 .
  • each auxiliary implant needle 20 includes one of a triangle, a rectangle, a circle, an ellipse, and a regular polygon.
  • the cross-sectional shape of the auxiliary implant needle 20 refers to the cross-sectional shape of the auxiliary implant needle 20 in the xy plane in Figure 1.
  • the cross-sectional shape is circular or oval, damage to brain tissue can be reduced, so it is preferred. .
  • each auxiliary implant needle 20 includes one or more of metal, alloy and non-metal.
  • Metals include, for example, tungsten.
  • Non-metals include, for example, silicon or silicon dioxide.
  • Examples of the alloy include platinum-iridium alloy, nickel-chromium alloy, and the like.
  • the auxiliary implant needle 20 is a rigid microwire, which is processed by optical fiber or tungsten wire with good collimation; or a silicon-based needle array obtained by deep silicon etching using a microelectromechanical system (MEMS) method; or The high aspect ratio SU-8 needle array structure is processed by MEMS technology. Further Ground, when using optical fiber or tungsten wire, it not only has high strength but also has good collimation.
  • MEMS microelectromechanical system
  • the diameter of the auxiliary implant needle 20 is 5 to 200 ⁇ m, for example, it can be 5 ⁇ m, 10 ⁇ m, 50 ⁇ m, or 100 ⁇ m. , 150 ⁇ m, 200 ⁇ m.
  • the larger the diameter D the greater the damage to brain tissue.
  • the diameter D is 50-150 ⁇ m, for example, it can be 50 ⁇ m, 75 ⁇ m, 100 ⁇ m, 125 ⁇ m, or 150 ⁇ m; further, for example, it is 75-100 ⁇ m.
  • the auxiliary implant needle 20 is processed by an etching process, for example.
  • the maximum diameter d of the tip of the auxiliary implant needle 20 is 1 to 100 ⁇ m, for example, it may be 1 ⁇ m, 10 ⁇ m, 50 ⁇ m, or 100 ⁇ m. In one example, the maximum diameter d is 10 to 100 ⁇ m, such as 10 ⁇ m, 20 ⁇ m, 50 ⁇ m, and 100 ⁇ m; further, for example, it is 20 to 50 ⁇ m.
  • the diameter difference between the two is 20-50 ⁇ m.
  • the diameter of the through hole 111 is 1 to 100 ⁇ m, for example, it may be 1 ⁇ m, 10 ⁇ m, 50 ⁇ m, or 100 ⁇ m. In one example, the diameter of the through hole 111 is 5-100 ⁇ m, such as 5 ⁇ m, 10 ⁇ m, 20 ⁇ m, 50 ⁇ m, 100 ⁇ m; further, for example, 20-50 ⁇ m. In the embodiment of the present disclosure, in order to ensure the cooperation between the tip 203 and the through hole 111, the diameter of the through hole 111 is greater than or equal to the diameter d of the tip and less than or equal to the diameter D of the auxiliary implant needle.
  • the fixation device 3 is configured to fix the assembled auxiliary implant end 201 and the auxiliary structure 11 .
  • the fixture 3 is located between the auxiliary implant end 201 and the auxiliary structure 11 to maintain the relative position between the auxiliary implant end 201 and the auxiliary structure 11 , thus ensuring that the flexible neural electrode 1 and the auxiliary implant assembly 3 No relative positional movement will occur during transportation.
  • the assembled flexible nerve electrode 1 and the auxiliary implant component 3 are fixed or connected together by using the fixture 3, which eliminates the need to attach the flexible nerve electrode 1 and the auxiliary implant during implantation.
  • the on-site assembly of the components 3 improves the implantation efficiency and shortens the operation time; in addition, since the flexible nerve electrode 1 and the auxiliary implant component 3 are assembled into an overall structure, they are easy to transport and use.
  • the fixed object 3 is configured so that its physical state changes with changes in external conditions.
  • at least one physical parameter used to characterize the physical state changes with changes in external conditions, and the physical parameter is, for example, volume.
  • the fixed object 3 can change from a solid state to a liquid state, thereby changing the volume.
  • the fixed object 3 when fixing 3 When a specific liquid is dropped, although the fixed object 3 remains solid, its volume changes from small to large (that is, swelling occurs).
  • the auxiliary implant component 2 and the flexible nerve electrode 1 are no longer bound together by the fixture 3 and are in a detachable state, which facilitates the subsequent operation of implanting the flexible nerve electrode.
  • the fixation 3 includes one or more of photo-melting materials, thermal melting materials, liquid-swelling materials and liquid-dissolving materials.
  • photo-melting materials include positive photosensitive resins, such as diazocain-based photosensitive resins.
  • positive photosensitive resins such as diazocain-based photosensitive resins.
  • the working principle is that the photosensitive film decomposes and denitrifies after being exposed to light. Through a molecular rearrangement reaction, it turns into acid when exposed to water.
  • thermally meltable materials include thermally meltable polymers such as polyethylene glycol (PEG) and polylactic acid-glycolic acid copolymer-polyethylene glycol (PLGA-PEG) one or more of them.
  • PEG polyethylene glycol
  • PLGA-PEG polylactic acid-glycolic acid copolymer-polyethylene glycol
  • liquid swellable materials include water-swellable polymers such as poly(ethylene glycol)alginate diacrylate (PEGDA) and poly(acrylamide)-alginate (PAAm). ) one or more.
  • PEGDA poly(ethylene glycol)alginate diacrylate
  • PAAm poly(acrylamide)-alginate
  • liquid-soluble materials include water-soluble polymers such as polyvinyl alcohol (PVA), fibroin, polyethylene glycol (PEG), polylactic acid-co-glycolic acid-polyethylene glycol (PLGA-PEG) and one or more of gelatin; the liquid includes one or more of ultrapure water, physiological saline and phosphate buffer (PBS).
  • PVA polyvinyl alcohol
  • PEG polyethylene glycol
  • PLGA-PEG polylactic acid-co-glycolic acid-polyethylene glycol
  • gelatin the liquid includes one or more of ultrapure water, physiological saline and phosphate buffer (PBS).
  • PBS physiological saline and phosphate buffer
  • concentration of the PVA solution is 2% to 10%, such as 2%, 5%, 10%, etc., such as 5%.
  • the fixture 3 is, for example, in the form of a membrane, and the membrane fixes the plurality of auxiliary implant ends 201 and the plurality of auxiliary structures 11 together.
  • the formation process of the fixture 3 can be simplified, that is, multiple auxiliary implant ends 201 and multiple auxiliary structures 11 are fixed together through a single film formation process.
  • the membrane at least fixes together the connections of the plurality of auxiliary implant ends 201 and the plurality of auxiliary structures 11 . This can reduce the amount of fixation material used and reduce the impact on the target tissue due to excessive use.
  • the thickness of the film is greater than the width of the connection along the z direction, for example, the thickness ranges from 30 to 50 ⁇ m.
  • the auxiliary implant assembly 2 further includes: an auxiliary fixing member 21 , which is located on a side of the plurality of auxiliary implant needles 20 away from the plurality of flexible nerve electrodes 1 and is configured to fix a plurality of Auxiliary implant needle 20.
  • an auxiliary fixing member 21 which is located on a side of the plurality of auxiliary implant needles 20 away from the plurality of flexible nerve electrodes 1 and is configured to fix a plurality of Auxiliary implant needle 20.
  • Figure 5 is a schematic structural diagram of an auxiliary implant component provided by an embodiment of the present disclosure.
  • the auxiliary fixation member 21 includes two auxiliary fixation plates 211.
  • the plane where the auxiliary fixation plates 211 are located is the xy plane, and the extension direction of the plurality of auxiliary implant needles 20 is the z direction. Therefore, the auxiliary fixation plates 211 are located on the xy plane.
  • the xy plane is perpendicular to the extending direction z of the plurality of auxiliary implant needles 20 .
  • Figure 5 only shows the situation where the plane of the auxiliary fixing plate 211 is perpendicular to the extension direction of the multiple auxiliary implant needles 20. It can be understood that in other embodiments of the present disclosure, the extension direction of the multiple auxiliary implant needles 20 It may not be parallel to the xy plane where the auxiliary fixation plate 211 is located. For example, the extension direction of the plurality of auxiliary implant needles 20 has a certain inclination angle relative to the xy plane. The inclination angle is, for example, greater than 0 degrees and less than or equal to 90 degrees. Likewise, It is beneficial to control the implantation depth of the flexible neural electrode, so the embodiment of the present disclosure does not limit this.
  • the auxiliary fixing plate 211 is detachably connected or fixedly connected to the plurality of auxiliary implant needles 20 .
  • detachable connection the number and position of the auxiliary implant needles 20 fixed on the auxiliary fixation plate 211 can be selected according to actual needs.
  • fixed connections are used, the stability of the entire flexible neural electrode composite structure can be improved.
  • Figure 6 is a schematic cross-sectional view of an auxiliary implant component according to another embodiment of the present disclosure.
  • an opening 212 is provided on the auxiliary fixing plate 211 .
  • the plurality of auxiliary implant needles 20 include a fixed end 202 away from the auxiliary implant end 201 along its extending direction.
  • the fixed end 202 is configured to pass through the opening 212 to connect with the auxiliary fixing plate 211.
  • the auxiliary implant assembly 2 further includes an adhesive 22 , at least part of the adhesive 22 is located between the auxiliary fixing plate 211 and the plurality of auxiliary implant needles 20 and connects the auxiliary fixing plate 211 and the plurality of auxiliary implants.
  • the insertion needles 20 are bonded to each other.
  • FIG. 6 shows the case of having two auxiliary fixing plates 211. It can be understood that the number of auxiliary fixing plates 211 can also be one or more, and the embodiment of the present disclosure does not limit this. Book In the embodiment, the use of two auxiliary fixing plates 211 with gaps can further ensure the alignment of the auxiliary implant needles and further improve the firmness between the auxiliary fixing plates 211 and the plurality of auxiliary implant needles 20 .
  • auxiliary implant needles 20 can be arranged in various ways.
  • a plurality of auxiliary implant needles 20 are arranged in an array.
  • the arrangement of the plurality of auxiliary implant needles 20 may be determined by the arrangement of the plurality of flexible nerve electrodes.
  • the auxiliary implant needle array is also arranged in a circular, square or polygonal shape to correspond to the multiple flexible neural electrodes 1 one-to-one.
  • FIG. 7 is a schematic structural diagram of a flexible neural electrode composite structure provided by another embodiment of the present disclosure.
  • the flexible nerve electrode composite structure 100a includes four flexible nerve electrodes 1a, an auxiliary implant component 2a and a fixation (not shown).
  • Four flexible neural electrodes 1a are arranged in a 2 ⁇ 2 array.
  • each flexible neural electrode 1a includes an implantation part 10a and an auxiliary structure 11a provided on the implantation part 10a.
  • the implant portion 10a is configured to be implanted into the target tissue under the action of external force.
  • the specific structure of the implanted part 10a of the flexible nerve electrode 1a can be referred to the description of the previous embodiment, and will not be repeated here.
  • восем ⁇ electrode sites 104a are provided on the implanted part 10a, and the eight electrode sites 104a are connected to eight conductive wires 103a in one-to-one correspondence for nerve recording or regulation.
  • the electrode sites 104a in Figure 7 are distributed on both sides of the implanted part 10a, which can increase the number of electrode sites per unit area, thereby enabling Record or regulate more signals.
  • each implant part 10 a is a linear structure
  • the extension direction of the plurality of auxiliary implant needles 20 is the z direction
  • the extension direction of the plurality of linear structures is the x direction. Therefore, the plurality of auxiliary implant needles 20 extend in the z direction.
  • the extending direction of the needle 20a is perpendicular to the extending directions of the plurality of linear structures.
  • Figure 7 only shows the situation where the extension direction of the auxiliary implant needle 20a is perpendicular to the extension direction of the implant part 10a of the flexible neural electrode 1a. It can be understood that in other embodiments of the present disclosure, the extension direction of the auxiliary implant needle 20a The extension direction can have a certain inclination angle relative to the extension direction of the linear structure. The inclination angle is, for example, greater than 0 degrees and less than or equal to 90 degrees, which is also beneficial to controlling flexible nerves.
  • the implantation depth of the electrode is not limited in this embodiment of the disclosure.
  • multiple flexible neural electrodes 1 may include multiple implant parts 10 , one part of the multiple implant parts 10 is a linear structure as shown in FIG. 7 , and the other part is a pullable structure as shown in FIG. 1 Extended spiral structure. In this way, different needs for implanted electrodes can be met during surgery. .
  • the implanted part can have a variety of shapes. Only linear structures and spiral structures are shown above, and other structures such as spring structures and mesh structures can also be included.
  • the shape of the spiral structure is not limited to the circle shown above, and can also be a triangle, a quadrilateral, a polygon, a rounded triangle, a rounded quadrilateral, a rounded polygon, and other other structures.
  • the flexible neural electrode composite structure 100 may also include a support assembly 4 .
  • the support component 4 connects the multiple implanted parts of the multiple flexible nerve electrodes 1 and plays a supporting role to facilitate the overall transfer of the multiple flexible nerve electrodes 1 .
  • the support assembly 4 includes a first support member 41 and a second support member 42 connected to the first support member 41 , wherein the first support member 41 includes the flexible insulating layer 101 and the conductive layer 102 of the flexible neural electrode 1 .
  • the second supporting component 42 only includes the flexible insulating layer 101, which plays an insulating role.
  • At least one embodiment of the present disclosure also provides a method of manufacturing a flexible neural electrode composite structure.
  • Figure 8 is a flow chart of a method for manufacturing a flexible neural electrode composite structure provided by an embodiment of the present disclosure. As shown in Figure 8, the manufacturing method of the flexible neural electrode composite structure 100 of Figure 1 provided by an embodiment of the present disclosure includes the following steps:
  • S100 Provide multiple flexible neural electrodes 1, each flexible neural electrode 1 including an implanted part 10 and an auxiliary structure 11 formed on the implanted part 10;
  • the auxiliary implant component 2 includes a plurality of auxiliary implant needles 20, and each auxiliary implant needle 20 includes an auxiliary implant end 201 located close to one end of the plurality of flexible nerve electrodes 1;
  • the manufacturing method of the flexible neural electrode composite structure provided by the embodiment of the present disclosure, by fixing the auxiliary implant component and the multiple flexible neural electrodes together, during the flexible neural electrode implantation process, multiple flexible neural electrodes can be implanted simultaneously. into the target organization.
  • the implantation time is shortened and the difficulty of implantation is reduced, thereby achieving the implantation of high-throughput and high-coverage flexible neural electrode arrays;
  • use fixtures to secure the The installed flexible nerve electrode and the auxiliary implant component are fixed or connected together, eliminating the need to assemble the flexible nerve electrode and the auxiliary implant component together on site during implantation, improving implantation efficiency and shortening operation time;
  • the flexible neural electrode and auxiliary implant components are assembled into an integral structure, they are easy to transport and use.
  • step S100 there are many methods to form the flexible neural electrode 1, such as photolithography process, micro-electromechanical system (MEMS), etc.
  • MEMS micro-electromechanical system
  • a method for preparing multiple flexible neural electrodes includes the following steps:
  • the substrate is a silicon wafer, which is cleaned ultrasonically, dried with nitrogen, and then cleaned with plasma.
  • S102 Form a plurality of grooves on the base, the plurality of grooves corresponding to the plurality of auxiliary structures 11 on the plurality of implant parts 10 of the plurality of flexible neural electrodes 1.
  • the auxiliary structure 11 can be a through hole, a groove or a protrusion. By providing multiple grooves, it is convenient to provide accommodating space for the auxiliary implant end 201 passing through the through hole when the auxiliary implant needle 20 is inserted into the through hole. , which is conducive to the transfer of electrodes.
  • S103 Form a sacrificial layer on the substrate on which multiple grooves are formed.
  • the sacrificial layer may be one or more of polymethyl methacrylate (PMMA), aluminum (Al), nickel (Ni), etc.
  • PMMA is used as the sacrificial layer, and the flexible neural electrode array is formed on the sacrificial layer.
  • the flexible neural electrode array is partially immersed in a solution such as acetone, the solution does not cover the PMMA sacrificial layer.
  • the PMMA sacrificial layer is completely dissolved, the flexible neural electrode array is released from the substrate.
  • S104 Form a flexible neural electrode array on the substrate on which the sacrificial layer is formed.
  • the flexible nerve electrode array includes a plurality of flexible nerve electrodes 1.
  • the flexible nerve electrode 1 includes a flexible insulating layer 101 and a conductive layer 102, wherein the conductive layer 102 includes a plurality of conductive lines 103; the flexible nerve electrode 1 also includes an implant portion 1 and Auxiliary structures 11 located on the implanted part 1 .
  • Electrode sites 104 are formed by removing portions of the flexible insulating layer 101 to expose portions of the conductive lines 103 .
  • the conductive layer 102 may be formed using a photolithography process.
  • the photolithography process includes, but is not limited to, coating photoresist, using a mask to expose Light, development, etching, stripping off remaining photoresist, etc.
  • the conductive layer 102 may have only one layer, or may have multiple layers. Each conductive layer 102 may be provided with multiple conductive lines 103 , and adjacent conductive layers 102 may be insulated from each other.
  • Figure 9 is a schematic structural diagram of a flexible neural electrode formed in the manufacturing method of a flexible neural electrode composite structure provided by an embodiment of the present disclosure.
  • FIG. 10 is a schematic cross-sectional view taken along line AA in FIG. 9 .
  • a circular groove 320 is formed in the silicon wafer 310 for accommodating the auxiliary implant needle passing through the auxiliary structure 11 b.
  • the circular groove 320 has a diameter of 60 ⁇ m and a depth of 100 ⁇ m.
  • a PMMA sacrificial layer 330 is formed on the silicon wafer 310 on which the circular groove 320 is formed.
  • a flexible neural electrode 1b is formed on the PMMA sacrificial layer 330.
  • the flexible nerve electrode 1b includes an implanted part 10b with a spiral structure.
  • the implanted portion 10b includes an auxiliary structure 11b (through hole 111b as shown in the figure) and an electrode site 104b.
  • the flexible neural electrode 1b also includes a conductive wire 103b connected to the electrode site 111b.
  • the diameter of the circular groove may be 5-100 ⁇ m, such as 5 ⁇ m, 10 ⁇ m, 20 ⁇ m, 25 ⁇ m, 30 ⁇ m, 40 ⁇ m, 50 ⁇ m, 100 ⁇ m, etc., for example, 40-60 ⁇ m;
  • the depth of the circular groove may be 1 -200 ⁇ m, such as 0 ⁇ m, 5 ⁇ m, 10 ⁇ m, 15 ⁇ m, 25 ⁇ m, 30 ⁇ m, 40 ⁇ m, 50 ⁇ m, 100 ⁇ m, 150 ⁇ m, 200 ⁇ m, etc., for example, 100-150 ⁇ m.
  • the thickness of the sacrificial layer is 0-20 ⁇ m, such as 1 ⁇ m, 2 ⁇ m, 5 ⁇ m, 10 ⁇ m, 20 ⁇ m, etc., for example, 1 ⁇ m.
  • step S200 may further include:
  • FIG. 11 to 13 are schematic cross-sectional views of a method for manufacturing an auxiliary implant component according to an embodiment of the present disclosure.
  • Figures 11 to 13 show the manufacturing process of the auxiliary implant component of Figure 6, which includes the following steps:
  • Each optical fiber 30 is composed of a high-purity silica (SiO2) core with a diameter of 125 ⁇ m and an acrylate coating with an outer diameter of 250 ⁇ m.
  • the optical fiber 30 is cut into fiber segments with a length of approximately 1 cm using a fiber cleaver, and approximately 50 ⁇ m of the acrylic coating at the tip is stripped off using a wire stripper.
  • three silicon wafers 2111 to 2113 are selected as auxiliary fixing plates, and multiple openings 212 are formed on each silicon wafer.
  • laser is used to etch the silicon wafer 2111 to obtain to a plurality of openings 212 arranged in a 3 ⁇ 4 array.
  • the 3 ⁇ 4 opening array is the same as the arrangement of the 3 ⁇ 4 through holes 111 of the flexible neural electrode array.
  • the diameter of the opening 212 is, for example, 260 ⁇ m.
  • multiple optical fibers 30 are inserted into the 12 openings 212 corresponding to the silicon wafers 2111 to 2113 for fixation and alignment.
  • the silicon wafers 2111 to 2112 play a role in collimating the plurality of optical fibers 30 , and the silicon wafer 2113 is used to fix the position of the optical fibers 30 .
  • the tip of the optical fiber 30 is etched with BOE (Buffered Oxide Etch) buffered oxide etching solution.
  • the etching process is as follows: first, etch the 125 ⁇ m core of the tip of the optical fiber 30 to a diameter of about 60 ⁇ m; then, take the optical fiber 30 out of the etching solution and clean it three times with deionized water, and immerse it in 50°C. Soak in absolute ethanol to remove the acrylate coating on the surface of the optical fiber 30; finally, continue to etch the optical fiber 30 with the acrylate coating removed using BOE buffered oxide etching solution to obtain an optical fiber with a tip diameter of approximately 20 ⁇ m.
  • the auxiliary implant component shown in Figure 6 is obtained.
  • step 4 tungsten wire can also be used as an auxiliary implant needle instead of the optical fiber 30 .
  • step 4 above can be replaced by step 4’) below:
  • step S300 the above manufacturing method further includes:
  • aligning at least one auxiliary implant end 201 of the plurality of auxiliary implant ends 201 with at least one auxiliary structure 11 of the plurality of auxiliary structures 11 is beneficial to more quickly assembling the auxiliary implant end 201 and the auxiliary structure 11 together.
  • the auxiliary implant component 2 is pre-fixed with a stereotaxic instrument, and the array of flexible neural electrodes 1 is adjusted on a rotating table to align the auxiliary implant component 2.
  • the rotating table is, for example, a multi-axis precision multi-axis device that can rotate at multiple angles. Air flotation turntable.
  • step S400 may further include: forming the fixation 3 at least at the connection between the auxiliary implant end 201 and the auxiliary structure 11, as shown in FIGS. 2 and 3 .
  • the fixture 3 is at least filled between the tip 203 of the auxiliary implant end 201 and the through hole 111, so that the relative position between the tip 203 and the through hole 111 remains unchanged.
  • the fixture 3 is formed into a membrane, and the membrane connects the plurality of auxiliary implant ends 201 and the plurality of auxiliary structures 11 together.
  • the specific material of the fixing object 3 reference can be made to the description of the previous embodiments and will not be described again here.
  • the following steps are performed:
  • the flexible neural electrode array Place the silicon wafer 310 formed with the circular groove 320, the PMMA sacrificial layer 330 and a plurality of flexible neural electrodes 1b (hereinafter referred to as the flexible neural electrode array) on a multi-axis precision air flotation turntable;
  • At least one embodiment of the present disclosure also provides a composite structural assembly, which includes a plurality of flexible neural electrode composite structures described in any of the foregoing embodiments.
  • Figure 14 is a schematic structural diagram of a composite structural component provided by an embodiment of the present disclosure.
  • the composite structure assembly 40 includes a plurality of flexible neural electrode composite structures 410 (for example, three as shown in the figure).
  • Each flexible neural electrode composite structure 410 has a structure similar to the flexible neural electrode composite structure shown in FIG. 1 . 100 same construction.
  • the composite structural assembly 40 further includes a connection portion 420 having a plurality of conductive lines. Each conductive Wires are connected between the electrode sites of the flexible neural electrode and the pads (not shown) to achieve signal transmission.
  • each flexible neural electrode composite structure uses a fixture to fix the auxiliary implant end and the auxiliary structure, the auxiliary implant assembly and multiple flexible neural electrodes are fixed together, so that in the flexible During the nerve electrode implantation process, multiple flexible nerve electrodes can be implanted 431 at the same time.
  • the implantation time is shortened and the difficulty of implantation is reduced, thereby achieving the implantation of high-throughput and high-coverage flexible neural electrode arrays; on the other hand, in the implantation of flexible Before the nerve electrode is installed, the assembled flexible nerve electrode and the auxiliary implant component are fixed or connected together with a fixation, which eliminates the need to assemble the flexible nerve electrode and the auxiliary implant component together on site during implantation, and improves the efficiency of the nerve electrode.
  • the implantation efficiency is improved and the operation time is shortened; in addition, because the flexible neural electrode and auxiliary implant components are assembled into a whole structure, they are easy to transport and use.
  • At least one embodiment of the present disclosure also provides a method for implanting a flexible neural electrode using the flexible neural electrode composite structure described in any of the previous embodiments.
  • Figure 15 is a method for implanting a flexible neural electrode using the flexible neural electrode composite structure of Figure 1 provided by an embodiment of the present disclosure.
  • the auxiliary implant component 2 when moving the auxiliary implant assembly 2 toward the target tissue, the plurality of implanted portions 10 of the plurality of flexible neural electrodes 1 move to the target tissue simultaneously.
  • the auxiliary implant component 2 can be lifted up to separate the auxiliary implant component 2 from the flexible nerve electrode 1 left on the target tissue. In this way, the auxiliary implant component 2 can be reused or directly throw away.
  • the flexible nerve electrodes left at the target tissue may be some or all of the plurality of flexible nerve electrodes 1 . When all of the flexible neural electrodes 1 are left at the target tissue, more electrode sites can be provided on the target tissue.
  • the auxiliary structure 11 when each implant portion 10 is a stretchable spiral structure, the auxiliary structure 11 is located on the stretchable spiral structure. In this way, when moving the auxiliary implant component 2 toward the target tissue to drive the multiple implant parts 10 of the multiple flexible neural electrodes 1 to move to the target tissue, the auxiliary implant end 201 can be used to push the auxiliary structure 11 downward, so that the auxiliary structure 11 can be pushed downward.
  • the stretched spiral structure unfolds in the z direction.
  • each implanted portion 10a is a linear structure, and the auxiliary structure 11a is located on the linear structure.
  • the auxiliary implant end 201a can be used to move the auxiliary structure 11a to drive the linear structure Move to target organization.
  • the flexible nerve electrode implantation method provided by the embodiments of the present disclosure, multiple flexible nerve electrodes can be implanted into the target tissue at the same time.
  • the implantation time is shortened and the difficulty of implantation is reduced, thereby achieving the implantation of high-throughput and high-coverage flexible neural electrode arrays;
  • the assembled flexible nerve electrode and the auxiliary implant component are fixed or connected together with a fixation, which eliminates the need to assemble the flexible nerve electrode and the auxiliary implant component together on site during implantation, and improves the efficiency of the nerve electrode.
  • the implantation efficiency is improved and the operation time is shortened; in addition, because the flexible neural electrode and auxiliary implant components are assembled into a whole structure, they are easy to transport and use.
  • a method of implanting flexible neural electrodes includes the following steps:
  • Rat anesthesia Take a healthy SPF rat and inject sodium pentobarbital according to the standard of 0.01g/mL to anesthetize the rat; after the rat is deeply anesthetized, fix it on the stereotaxic instrument and follow-up
  • Use gas anesthesia for small animals use cotton swabs dipped in iodophor to apply disinfection on the rat's head, and cut off the hair; use scissors to cut off the rat's scalp along the middle seam, clean the surface tissue of the skull, and expose the clean skull.
  • Craniotomy window Use a cranial drill to drill a 5mm x 7mm rectangular cranial window 2.5mm before and after the anterior fontanel and 3.5mm left and right of the midline of the rat, and carefully remove the dura mater to provide a location for implanting flexible neural electrodes. .
  • Electrode implantation Fix the flexible neural electrode composite structure fixed with PVA film prepared in any of the previous embodiments on the stereotaxic instrument, and gradually approach it into the cranial window of the rat brain surface; wait for the flexible neural electrode array After the PVA film is in contact with the brain surface, drop physiological saline into the gap between the PVA film and the silicon wafer to dissolve the PVA film; after the PVA film is dissolved and the flexible neural electrode is completely released, start When electrode implantation begins, the stereotaxic clamping rod descends at a speed of approximately 20 ⁇ m/s.
  • the descent height is about 1mm, that is, the height after the fiber tip contacts the brain surface
  • At least one embodiment of the present disclosure also provides a method for implanting flexible neural electrodes using the composite structure assembly described in the previous embodiment, including: using multiple flexible neural electrode composite structures to implant multiple sets of flexible neural electrodes into target tissues. , each set of flexible neural electrodes includes multiple flexible neural electrodes.
  • the implantation method includes using a plurality of flexible neural electrode composite structures 410 to sequentially implant a first group of flexible nerve electrodes 431, a second group of flexible nerve electrodes 432, and a third group of flexible nerve electrodes 433 into the target tissue.
  • each group of flexible nerve electrodes includes, for example, 12 flexible nerve electrodes.
  • multiple flexible nerve electrode composite structures 410 can also be used to simultaneously implant the first group of flexible nerve electrodes 431, the second group of flexible nerve electrodes 432, and the third group of flexible nerve electrodes 433 into the target tissue.
  • the auxiliary implant assembly 2 includes: an auxiliary fixator 21 including at least one auxiliary fixation plate 211 ; a plurality of auxiliary implant needles 20 configured to be connected to the at least one auxiliary fixation plate 211 , the extension direction of the plurality of auxiliary implant needles 20 (z direction as shown in the figure) is not parallel to the plane where at least one auxiliary fixation plate 211 is located (xy plane as shown in the figure).
  • connection between at least one auxiliary fixing plate 211 and the plurality of auxiliary implant needles 20 is detachable or fixed.
  • at least one auxiliary fixing plate 211 is provided with an opening 212
  • the plurality of auxiliary implant needles 20 include a fixed end 202 arranged opposite to the auxiliary implant end 201.
  • the fixed end 202 is configured to pass through the opening 212 to connect with at least one The auxiliary fixing plate 211 is connected.
  • the auxiliary implant assembly 2 further includes: an adhesive 22 , at least part of the adhesive 22 is located between at least one auxiliary fixation plate and a plurality of auxiliary implant needles 20 .
  • the implantable flexible neural electrode array can be transferred and implanted as a whole.
  • the array implantation and transfer method can greatly improve the transfer and release. and implantation efficiency, reducing implantation time and time, and providing a simple and efficient method for large-scale implantation of implantable flexible neural electrode arrays.
  • the implantation speed is 1 to 200 ⁇ m/s (micron/second), such as 1 ⁇ m/s, 5 ⁇ m/s, 10 ⁇ m/s, 15 ⁇ m/s, 20 ⁇ m/s, 30 ⁇ m/s, 50 ⁇ m/s, 100 ⁇ m/s, 200 ⁇ m/s, for example, 10 ⁇ m/s to 20 ⁇ m/s.

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Abstract

一种柔性神经电极复合结构及制造、植入方法和辅助植入组件。上述柔性神经电极复合结构(100)，包括：多个柔性神经电极(1)，每个所述柔性神经电极(1)包括植入部分(10)和设置于所述植入部分(10)的辅助结构(11)；辅助植入组件(2)，包括与所述多个柔性神经电极(1)一一对应的多个辅助植入针(20)，每个所述辅助植入针(20)包括位于靠近与其对应的柔性神经电极(1)一端的辅助植入端(201)，所述辅助植入端(201)构造为与所述辅助结构(11)组装；和固定物(3)，构造为将组装的所述辅助植入端(201)和所述辅助结构(11)固定。利用固定物(3)将辅助植入组件(2)和多个柔性神经电极(1)固定在一起，从而能同时将多个柔性神经电极(1)植入到目标组织，实现高通量、高覆盖率的柔性神经电极阵列的植入。

Description

柔性神经电极复合结构及制造、植入方法和辅助植入组件
相关申请的交叉引用
本申请基于并且要求于2022年4月2日递交、名称为“柔性神经电极复合结构及制造、植入方法和辅助植入组件”的中国专利申请第202210351875.0号的优先权，在此全文引用上述中国专利申请公开的内容以作为本申请的一部分。
技术领域
本公开涉及神经科学技术领域，尤其涉及一种柔性神经电极复合结构及其制造方法和植入方法、复合结构组件及其植入方法、以及辅助植入组件。
背景技术
近年来，作为大脑功能解析、脑部疾病治疗以及脑机接口的重要工具，植入式神经电极得到了快速的发展。然而，由于传统的植入式神经电极都是刚性的，与脑组织的力学性能不匹配，在其植入大脑以后，两者之间会在呼吸和运动的影响下产生相互运动，从而对电极周围的脑组织会产生较大的损伤，并进而引发炎症反应。当免疫增生的细胞包裹电极表面，会使得脑电极记录信号不断减弱，直至失效。
相比刚性神经电极，柔性神经电极具有与神经组织更加匹配的力学性能，可减小对脑组织的免疫损伤，从而提高神经信号检测的稳定性，能够用于脑电信号的长时记录。然而，如何实现柔性神经电极在大脑(和其他神经组织)的高通量、大范围植入，是目前亟待解决的问题。
发明内容
本公开实施例提供一种柔性神经电极复合结构及其制造方法和植入方法、复合结构组件及其植入方法、以及辅助植入组件。
根据本公开第一方面，提供一种柔性神经电极复合结构，包括：多个柔性神经电极，每个所述柔性神经电极包括植入部分和设置于所述植入部分的 辅助结构；辅助植入组件，包括与所述多个柔性神经电极一一对应的多个辅助植入针，每个所述辅助植入针包括位于靠近与其对应的柔性神经电极一端的辅助植入端，所述辅助植入端构造为与所述辅助结构组装；和固定物，构造为将组装的所述辅助植入端和所述辅助结构固定。
根据本公开第二方面，提供一种柔性神经电极复合结构的制造方法，包括：提供多个柔性神经电极，每个所述柔性神经电极包括植入部分和形成于所述植入部分上的辅助结构；形成辅助植入组件，所述辅助植入组件包括多个辅助植入针，每个所述辅助植入针包括位于靠近所述多个柔性神经电极一侧的辅助植入端；组装所述辅助植入端与所述辅助结构；和固定组装的所述辅助植入端和所述辅助结构。
根据本公开第三方面，提供一种采用前述的柔性神经电极复合结构的柔性神经电极的植入方法，包括：移动所述柔性神经电极复合结构，以带动所述多个柔性神经电极的植入部分移动到目标组织的表面；融解或溶解所述固定物，以使所述辅助植入端与所述辅助结构处于可分离状态；向所述目标组织移动所述辅助植入组件，以带动所述多个柔性神经电极的多个植入部分移动到所述目标组织；以及移去所述辅助植入组件，并且将所述多个柔性神经电极留在所述目标组织处。
根据本公开第四方面，提供一种复合结构组件，包括前述的柔性神经电极复合结构。
根据本公开第五方面，提供一种采用前述的复合结构组件的柔性神经电极的植入方法，包括：利用所述多个柔性神经电极复合结构将多组柔性神经电极植入到目标组织，每组柔性神经电极包括多个柔性神经电极。
根据本公开第六方面，提供一种辅助植入组件，包括：辅助固定件，所述辅助固定件包括至少一个辅助固定板；多个辅助植入针，构造为与所述至少一个辅助固定板连接，所述多个辅助植入针的延伸方向与所述至少一个辅助固定板所在的平面不平行。
附图说明
为了更清楚地说明本公开实施例的技术方案，下面将对实施例的附图作简单地介绍，显而易见地，下面描述中的附图仅仅涉及本公开的一些实施例， 而非对本公开的限制。
图1为本公开实施例提供的柔性神经电极复合结构的立体示意图。
图2为图1的柔性神经电极复合结构沿虚线平面a截取的截面示意图。
图3为图2中柔性神经电极复合结构的局部放大示意图。
图4A为图1的柔性神经电极复合结构的区域b的局部立体结构示意图。
图4B为图1的柔性神经电极阵列的俯视图。
图5为本公开实施例提供的辅助植入组件的结构示意图。
图6为本公开另一实施例的辅助植入组件的截面示意图。
图7为本公开另一实施例提供的柔性神经电极复合结构的结构示意图。
图8为本公开实施例提供的柔性神经电极复合结构的制造方法的流程图。
图9为本公开实施例提供的柔性神经电极复合结构的制造方法中形成的柔性神经电极的结构示意图。
图10为沿图9的AA线截取的截面示意图。
图11至图13为本公开实施例提供的辅助植入组件的制作方法的截面示意图。
图14为本公开实施例提供的复合结构组件的结构示意图。
图15为本公开实施例提供的采用图1的柔性神经电极复合结构的柔性神经电极的植入方法。
具体实施方式
为使本公开实施例的目的、技术方案和优点更加清楚，下面将结合本公开实施例的附图，对本公开实施例的技术方案进行清楚、完整地描述。显然，所描述的实施例是本公开的一部分实施例，而不是全部的实施例。基于所描述的本公开的实施例，本领域普通技术人员在无需创造性劳动的前提下所获得的所有其他实施例，都属于本公开保护的范围。
除非另作定义，此处使用的技术术语或者科学术语应当为本公开所属领域内具有一般技能的人士所理解的通常意义。本公开专利申请说明书以及权利要求书中使用的“第一”、“第二”以及类似的词语并不表示任何顺序、数量或者重要性，而只是用来区分不同的组成部分。“包括”或者“包含”等类似的 词语意指出现在“包括”或者“包含”前面的元件或者物件涵盖出现在“包括”或者“包含”后面列举的元件或者物件及其等同，并不排除其他元件或者物件。“连接”或者“相连”等类似的词语并非限定于物理的或者机械的连接，而是可以包括电性的连接，不管是直接的还是间接的。“上”、“下”、“左”、“右”等仅用于表示相对位置关系，当被描述对象的绝对位置改变后，则所述相对位置关系也可能相应地改变。
为了在大空间尺度上与神经组织紧密稳定地结合，需要制备高通量、高覆盖率的柔性神经电极阵列。但是，目前的柔性神经电极的植入过程受限于冗长的植入操作和有限的电极植入面积。例如，当对柔性神经电极阵列采用单根逐一植入时，不仅耗时耗力，而且由于手术过程中开颅时间过长，易引发术中和术后并发症。
为此，本公开实施例提供一种柔性神经电极复合结构及其制造方法和植入方法、复合结构组件及其植入方法、以及辅助植入组件，通过采用具有辅助植入组件的柔性神经电极复合结构实现高通量植入，降低植入难度，并缩短手术时间。
本公开至少一个实施例提供一种柔性神经电极复合结构，包括：多个柔性神经电极，每个柔性神经电极包括植入部分和设置于植入部分的辅助结构；辅助植入组件，包括与多个柔性神经电极一一对应的多个辅助植入针，每个辅助植入针包括位于靠近与其对应的柔性神经电极一端的辅助植入端，辅助植入端构造为与所述辅助结构组装；和固定物，构造为将组装的辅助植入端和辅助结构固定。
本公开实施例提供的柔性神经电极复合结构中，利用固定物固定辅助植入端和辅助结构，从而将辅助植入组件和多个柔性神经电极固定在一起，这样在柔性神经电极植入过程中，可同时将多个柔性神经电极植入到目标组织。相比于单根逐一的植入方法，一方面，缩短植入时间，降低植入难度，从而实现高通量、高覆盖率的柔性神经电极阵列的植入；另一方面，在植入柔性神经电极之前，利用固定物把组装后的柔性神经电极和辅助植入组件固定或连接在一起，省去了在植入时将柔性神经电极和辅助植入组件现场组装在一起的操作，提高了植入效率，缩短手术时间；另外，由于柔性神经电极和辅助植入组件为组装好的整体结构，便于运输和使用。本公开实施例中，“多个” 指的是两个或两个以上。
本公开实施例中，多个柔性神经电极可排列为一排或多排，从而形成柔性神经电极阵列。多个辅助植入针也可以排列为一排或多排，从而形成辅助植入针阵列。例如，辅助植入针阵列为三维空间排布得到的光纤、钨丝、铂铱合金丝、镍铬合金丝阵列；或用微机电系统(MEMS,Micro-Electro-Mechanical System)制备的硅针阵列；或通过深硅刻蚀得到的梳齿状阵列；或通过MEMS加工得到的针状阵列。
下面通过几个具体的实施例对本公开进行说明。为了保持本公开实施例以下的说明清楚且简明，可省略已知功能和已知部件的详细说明。当本公开实施例的任一部件在一个以上的附图中出现时，该部件在每个附图中可以由相同的参考标号表示。
图1为本公开实施例提供的柔性神经电极复合结构的立体示意图。
如图1所示，柔性神经电极复合结构100包括多个柔性神经电极1(即柔性神经电极阵列)、辅助植入组件2和固定物3。
例如，每个柔性神经电极1包括植入部分10和设置于植入部分10的辅助结构11。植入部分10构造为在外力的作用下植入到目标组织，例如人或动物的脑组织。
图2为图1的柔性神经电极复合结构沿虚线平面a截取的截面示意图。图3为图2中柔性神经电极复合结构的局部放大示意图。
如图3所示，柔性神经电极1的植入部分10例如包括柔性绝缘层101和埋设在柔性绝缘层101中的至少一个导电层102。例如，导电层102包括多条导电线103。多条导电线103之间通过柔性绝缘层101彼此绝缘。如图4所示，植入部分10上设置有多个电极位点104，多个电极位点104与多条导电线103一一对应地连接，用于神经记录或者调控。导电线103的数量越多，柔性神经电极1的电极位点104越多，进行信号记录的范围也越大。在一个示例中，电极位点104通过去除部分柔性绝缘层101以暴露导电线103的方式形成。
图3和图4A的每个植入部分10仅示出10个电极位点104和与其连接的10条导电线103，可以理解的是，本公开其他实施例中，每个植入部分10的电极位点104的数量和导电线103的数量可根据实际需要来确定，本公开 实施例对此不做限定。
本公开实施例中，多个柔性神经电极1的多个植入部分10的排列方式可以有多种。图4B为图1的多个柔性神经电极的俯视图。如图4B所示，多个植入部分10排列为4×3的阵列形式，然而本公开实施例不限于此，多个植入结构10还可以排列为m行n列，其中m大于等于1，n大于等于1。
图4B的柔性神经电极阵列中，每个盘旋结构的直径为大约1mm。每根柔性神经电极的宽度为大约15μm，每根柔性神经电极分布有10个检测位点(即电极位点104)，其中植入部分共分五层结构(绝缘层/导电层/绝缘层/导电层/绝缘层)。柔性神经电极整体厚度为大约2.5μm。植入部分10位于每根柔性神经电极1的前端，每根柔性神经电极1的后端设置有与每个电极位点104对应的焊盘，焊盘连接到外部电路。
如图2和图3所示，植入部分10设置有辅助结构11，辅助结构11构造为与辅助植入组件2连接。例如，辅助结构11与辅助植入组件2之间通过插接方式相互连接。
如图1所示，辅助植入组件2例如包括与多个柔性神经电极1一一对应的多个辅助植入针20，每个辅助植入针20包括辅助植入端201和固定端202，其中辅助植入端201位于辅助植入针20的靠近柔性神经电极1的一端，固定端202位于辅助植入针20的远离柔性神经电极1的另一端。辅助植入端201构造为与辅助结构11组装，这样，可将柔性神经电极1与辅助植入组件2组装在一起。
本公开实施例中，多个柔性神经电极1与辅助植入组件2之间利用组装好的辅助植入端201和辅助结构11来实现连接，有利于通过辅助植入组件2批量植入多个柔性神经电极1，从而实现高通量、高覆盖率的电极植入。
本公开实施例中，多个辅助植入针20的延伸方向与多个柔性神经电极1的多个植入部分10的延伸方向不平行。换言之，多个辅助植入针20的延伸方向与多个柔性神经电极1的多个植入部分10的延伸方向为空间交叉，即二者可以相交，也可以不相交。
例如，如图1和图2所示，多个辅助植入针20相互平行且沿z方向延伸。每个柔性神经电极1的植入部分10例如为可拉伸的盘旋结构，盘旋结构所在的平面为xy平面。辅助植入针20的延伸方向z与盘旋结构所在的xy平面不 平行，例如为相互垂直。这样，当植入柔性神经电极时，通过使多个辅助植入针20的延伸方向与多个柔性神经电极1的多个植入部分10的延伸方向相互垂直，有利于控制柔性神经电极的植入深度，从而使柔性神经电极到达目标组织。
图1和图2仅示出了辅助植入针20的延伸方向与柔性神经电极的植入部分10的延伸方向相互垂直的情况，可以理解的是，本公开其他实施例中，辅助植入针20的延伸方向可相对盘旋结构所在的xy平面具有一定倾斜角度，该倾斜角度例如为大于0度且小于或者等于90度，同样有利于控制柔性神经电极的植入深度，因此本公开实施例对此不做限定。
如图1和图4A所示，当每个柔性神经电极1的植入部分10为可拉伸的盘旋结构时，有利于在植入柔性神经电极1的过程中，利用辅助植入组件2将盘旋结构展开，从而灵活调整柔性神经电极1的植入深度，进一步降低植入难度。
本公开实施例中，在忽略盘旋结构在z方向的厚度的情况下，盘旋结构可以为图1所示的二维平面结构，还可以为三维立体结构，即沿z方向盘旋为立体形状，本公开对此不做限定。进一步地，当盘旋结构为图1所示的二维平面结构时，盘旋结构例如具有圆形、三角形、四边形、多边形或圆角三角形、圆角四边形、圆角多边形等，优选地，该盘旋结构具有圆形，该圆形可形成为半圆(即1/2圈)、2/3圆或至少一个圆等等，本领域技术人员可根据植入深度的实际需要，确定盘旋结构的圈数，本公开实施例对此不做限定。当圈数增多时，可增加植入深度或植入长度。
本公开实施例中，辅助结构11位于盘旋结构的端部处，即植入部分10的末端，这样有利于在柔性神经电极的植入过程中，更容易牵引或拉动盘旋结构展开。可以理解的是，在本公开其他实施例中，辅助结构11还可以位于植入部分10的端部的其他位置(例如图4A的两个电极位点104之间的C1位置)，或者位于植入部分10的远离末端的部分(例如图4A的C2位置)，同样能够使柔性神经电极伸长或展开，因此本公开实施例对辅助结构11的位置不做限定。
图1和图2仅示出了植入部分10为可拉伸的盘旋结构，可以理解的是，在本公开其他实施例中植入部分10还可以具有其他形状，例如直线形结构或 波浪形结构等。例如，植入部分10可为盘旋结构、波浪形结构和直线形结构中的一种或多种。
本公开实施例中，辅助植入端201和辅助结构11之间为拆卸地组装在一起，例如通过插接方式组装在一起，这样便于安装和拆卸。
例如，如图2所示，辅助植入端201和辅助结构11通过插接方式组装在一起。辅助结构11例如为位于植入部分10上的通孔111。为便于插入通孔111中，辅助植入端201包括尖端203，该尖端203的直径小于或等于辅助植入针20的直径。
例如，该尖端203具有朝辅助结构11逐渐缩小的横截面，例如图中所示的锥形，该锥形可以为圆锥或棱锥。这样，当组装辅助植入端201和辅助结构11时，尖端203可起到导向作用，利于快速插入辅助结构11进行组装。尖端203也可以为平头，本公开实施例对此尖端203的形状不做具体限定。
图4A仅示出了辅助结构11为通孔的情况，本公开其他实施例中，辅助结构11还可以是凹槽或凸起，只要能和辅助植入端201插接在一起的结构，均包含在本公开实施例中。
本公开实施例中，辅助植入端201部分或全部插入辅助结构11中。例如，当将辅助植入端201全部插入辅助结构11时，可提高组装后的牢固性；当将辅助植入端201部分插入辅助结构11中时，方便在植入柔性神经电极1后，对柔性神经电极1和辅助植入组件2进行分离。如图3所示，辅助植入端201部分插入通孔111中，也就是尖端203插入到通孔111中。
本公开实施例中，每个辅助植入针20的截面形状包括三角形、长方形、圆形、椭圆形和正多边形中的一种。辅助植入针20的截面形状是指图1中的辅助植入针20在xy平面内的截面形状，当该截面形状为圆形或椭圆形时，可降低对脑组织的损伤，因此为优选。
本公开实施例中，每个辅助植入针20的材料包括金属、合金和非金属中的一种或多种。金属例如包括钨。非金属例如包括硅或二氧化硅。合金例如包括铂铱合金或镍铬合金等。
例如，辅助植入针20例如为刚性微丝，采用准直性好的光纤、钨丝进行加工；或通过微机电系统(MEMS)的方法进行深硅刻蚀得到的硅基针状阵列；或通过MEMS技术加工得到的高深宽比的SU-8针状阵列结构。进一步 地，当采用光纤或钨丝时，不仅强度高而且准直性好。
本公开实施例中，辅助植入针20的截面形状为圆形时，辅助植入针20的直径(图3中所示直径D)为5～200μm，例如可以是5μm、10μm、50μm、100μm、150μm、200μm。如果直径D越大，对脑组织的损伤越大。在一个示例中，直径D为50～150μm，例如可以是50μm、75μm、100μm、125μm、150μm；进一步地，例如为75～100μm。辅助植入针20例如通过刻蚀工艺加工而成。
本公开实施例中，辅助植入针20的尖端的最大直径d为1～100μm,例如可以是1μm、10μm、50μm、100μm。在一个示例中，最大直径d为10～100μm,如10μm，20μm，50μm，100μm；进一步地，例如为20～50μm。
本公开实施例中，辅助植入针20的尖端203和辅助植入针201的直径差越大越好，例如二者的直径差为20～50μm。
本公开实施例中，通孔111的直径为1～100μm,例如可以是1μm、10μm、50μm、100μm。在一个示例中，通孔111的直径为5～100μm，如5μm，10μm，20μm，50μm，100μm；进一步地，例如为20～50μm。本公开实施例中，为了保证尖端203和通孔111之间的配合，通孔111的直径大于或者等于尖端的直径d且小于或等于辅助植入针的直径D。
如图1至图3所示，固定物3构造为将组装的辅助植入端201和辅助结构11固定。例如，固定物3的至少一部分位于辅助植入端201和辅助结构11之间以保持辅助植入端201和辅助结构11之间的相对位置，这样可保证柔性神经电极1和辅助植入组件3在运输过程中不会发生相对位置移动。而且，在植入柔性神经电极之前，利用固定物3把组装后的柔性神经电极1和辅助植入组件3固定或连接在一起，省去了在植入时将柔性神经电极1和辅助植入组件3现场组装在一起的操作，提高植入效率，缩短手术时间；另外，由于柔性神经电极1和辅助植入组件3为组装好的整体结构，便于运输和使用。
本公开实施例中，固定物3构造为其物理状态随着外界条件的改变而变化。例如，用于表征物理状态的至少一个物理参数随着外界条件的改变而变化，该物理参数例如为体积。一个示例中，改变光照或环境温度，固定物3可由固态变化为液态，由此体积发生了变化。另一个示例中，当在固定物3 滴下特定液体时，固定物3虽保持固态不变，但体积由小变大(即发生溶胀现象)。当固定物3的物理状态发生变化时，辅助植入组件2和柔性神经电极1不再被固定物3束缚在一起，二者处于可分离状态，这样便于后续植入柔性神经电极的操作。
本公开实施例中，固定物3包括光融解材料、热融解材料、液体溶胀材料和液体溶解材料中的一种或多种。
例如，光融解材料包括正性感光性树脂，例如重氮蔡醒系感光树脂，工作原理是感光膜经光照后曝光部分分解脱氮，通过分子重排反应，遇水成酸。
例如，热融解材料包括热融解聚合物，例如聚乙二醇(polyethylene glycol，PEG)和聚乳酸-羟基乙酸共聚物-聚乙二醇(Polylactic acid-glycolic acid copolymer-polyethylene glycol，PLGA-PEG)中的一种或多种。
例如，液体溶胀材料包括水溶胀聚合物，例如聚(乙二醇)海藻酸二丙烯酸酯(poly(ethylene glycol)alginate diacrylate，PEGDA)和聚(丙烯酰胺)-海藻酸盐(polyacrylamide-alginate，PAAm)中的一种或多种。
例如，液体溶解材料包括水溶解聚合物，例如聚乙烯醇(polyvinyl alcohol，PVA)、蚕丝蛋白、聚乙二醇(PEG)、聚乳酸-羟基乙酸共聚物-聚乙二醇(PLGA-PEG)和明胶中的一种或多种；液体包括超纯水、生理盐水和磷酸盐(PBS)缓冲液中的一种或多种。当选用PVA溶液时，PVA溶液的浓度为2％～10％，例如为2％、5％、10％等，例如为5％。
如图1至图3所示，固定物3例如采用膜的形式，膜将多个辅助植入端201和多个辅助结构11固定在一起。这样，可简化固定物3的形成工艺，即通过一次成膜工艺将多个辅助植入端201和多个辅助结构11固定在一起。例如，该膜至少将多个辅助植入端201和多个辅助结构11的多个连接处固定在一起。这样可减小固定材料的用量，减少由于用量多对目标组织的影响。例如，该膜的厚度大于连接处沿z方向的宽度，例如厚度的取值范围为30-50μm。
如图1和图2所示，辅助植入组件2还包括：辅助固定件21，辅助固定件21位于多个辅助植入针20远离多个柔性神经电极1的一侧并且构造为固定多个辅助植入针20。通过设置辅助固定件21，可将多个柔性神经电极1连接到同一对象，这样在植入时，医生可通过抓住辅助固定件来整体移动或 整体植入多个柔性神经电极1。
图5为本公开实施例提供的辅助植入组件的结构示意图。
如图5所示，例如，辅助固定件21包括两个辅助固定板211，辅助固定板211所在平面为xy平面，多个辅助植入针20的延伸方向为z方向，因此辅助固定板211所在的xy平面与多个辅助植入针20的延伸方向z相互垂直。通过将辅助固定板211所在平面与多个辅助植入针20的延伸方向设置为相互垂直，有利于在植入柔性神经电极的过程中，方便控制柔性神经电极的植入深度。
图5仅示出了辅助固定板211所在平面与多个辅助植入针20的延伸方向相互垂直的情况，可以理解的是，本公开其他实施例中，多个辅助植入针20的延伸方向可与辅助固定板211所在的xy平面不平行，例如，多个辅助植入针20的延伸方向相对xy平面具有一定的倾斜角度，该倾斜角度例如为大于0度且小于或等于90度，同样有利于控制柔性神经电极的植入深度，因此本公开实施例对此不做限定。
例如，辅助固定板211与多个辅助植入针20之间为可拆卸连接或固定连接。当采用可拆卸连接时，可根据实际需要选择固定到辅助固定板211上的辅助植入针20的数量和位置。当采用固定连接时，可提高整个柔性神经电极复合结构的稳固性。
图6为本公开另一实施例的辅助植入组件的截面示意图。
如图6所示，辅助固定板211上设置有开孔212，多个辅助植入针20包括沿其延伸方向远离辅助植入端201的固定端202，固定端202构造为穿过开孔212以与辅助固定板211连接。通过在辅助固定板211上设置开孔212，有利于辅助植入针20与辅助固定板211之间实现可拆卸连接。
如图6所示，辅助植入组件2还包括粘合剂22，至少部分粘合剂22位于辅助固定板211和多个辅助植入针20之间并将辅助固定板211和多个辅助植入针20相互粘结。通过设置粘合剂22，可提高辅助固定板211和多个辅助植入针20之间的牢固性，避免柔性神经电极复合结构在移动过程中发生辅助植入针20的脱落或偏移，影响植入效果。
图6中示出了具有两个辅助固定板211的情况，可以理解的是，辅助固定板211的数量还可以是一个或两个以上，本公开实施例对此不做限定。本 实施例中，采用具有间隙的两个辅助固定板211，可进一步保证辅助植入针的准直性，同时进一步提高辅助固定板211和多个辅助植入针20之间的牢固性。
本公开实施例中，多个辅助植入针20可以多种方式排列。例如，图5中，多个辅助植入针20排列为阵列形式。然而在其他实施例中，多个辅助植入针20的排列方式可由多个柔性神经电极的布置方式决定。例如，当多个柔性神经电极阵列布置为圆形、方形或多边形时，辅助植入针阵列也排列为圆形、方形或多边形以与多个柔性神经电极1一一对应。
图7为本公开另一实施例提供的柔性神经电极复合结构的结构示意图。如图7所示，柔性神经电极复合结构100a包括四个柔性神经电极1a、辅助植入组件2a和固定物(未示出)。四个柔性神经电极1a排列为2×2的阵列。
例如，每个柔性神经电极1a包括植入部分10a和设置于植入部分10a的辅助结构11a。植入部分10a构造为在外力的作用下植入到目标组织。柔性神经电极1a的植入部分10a的具体结构可参见前面实施例的描述，此处不再重复。
如图7所示，植入部分10a上设置有8个电极位点104a，8个电极位点104a与8条导电线103a一一对应地连接，用于神经记录或者调控。与图4A中电极位点104位于植入部分10的单侧相比，图7中电极位点104a分布在植入部分10a的两侧，可在单位面积内增加电极位点的数目，从而可记录或者调控更多信号。
如图7所示，每个植入部分10a为直线形结构，多个辅助植入针20的延伸方向为z方向，多个直线形结构的延伸方向为x方向，因此，多个辅助植入针20a的延伸方向与多个直线形结构的延伸方向相互垂直。这样，当植入柔性神经电极时，通过使多个辅助植入针20a的延伸方向与多个柔性神经电极1a的多个植入部分10a的延伸方向相互垂直，有利于控制柔性神经电极的植入深度，从而使柔性神经电极到达目标组织。
图7仅示出了辅助植入针20a的延伸方向与柔性神经电极1a的植入部分10a的延伸方向相互垂直的情况，可以理解的是，本公开其他实施例中，辅助植入针20a的延伸方向可相对直线形结构的延伸方向具有一定倾斜角度，该倾斜角度例如为大于0度且小于或者等于90度，同样有利于控制柔性神经 电极的植入深度，因此本公开实施例对此不做限定。
本公开实施例中，多个柔性神经电极1可包括多个植入部分10，多个植入部分10中的一部分为图7所示的直线形结构，另一部分为图1所示的可拉伸的盘旋结构。这样，可在手术中满足对植入电极的不同需求。。
本公开实施例中，植入部分的形状可以有多种，以上仅示出了直线形结构和盘旋结构，还可以包括弹簧结构、网状结构等其他结构。另外，盘旋结构的形状也不局限于以上所示的圆形，还可以三角形、四边形、多边形或圆角三角形、圆角四边形、圆角多边形等等其他构造。
返回图4B，柔性神经电极复合结构100还可以包括支撑组件4。支撑组件4连接多个柔性神经电极1的多个植入部分，起到支撑作用，方便对多个柔性神经电极1进行整体转移。支撑组件4包括第一支撑部件41和与第一支撑部件41连接的第二支撑部件42，其中，第一支撑部件41包括柔性神经电极1的柔性绝缘层101和导电层102。第二支撑部件42仅包括柔性绝缘层101，起到绝缘作用。
本公开至少一个实施例还提供一种柔性神经电极复合结构的制造方法。
图8为本公开实施例提供的柔性神经电极复合结构的制造方法的流程图。如图8所示，本公开实施例提供的图1的柔性神经电极复合结构100的制造方法，包括以下步骤：
S100：提供多个柔性神经电极1，每个柔性神经电极1包括植入部分10和形成于植入部分10上的辅助结构11；
S200：形成辅助植入组件2，辅助植入组件2包括多个辅助植入针20，每个辅助植入针20包括位于靠近多个柔性神经电极1一端的辅助植入端201；
S300：组装辅助植入端201与辅助结构11；和
S400：固定组装的辅助植入端201和辅助结构11。
本公开实施例提供的柔性神经电极复合结构的制造方法中，通过将辅助植入组件和多个柔性神经电极固定在一起，在柔性神经电极植入过程中，可同时将多个柔性神经电极植入到目标组织。相比于单根逐一的植入方法，一方面，缩短植入时间，降低植入难度，从而实现高通量、高覆盖率的柔性神经电极阵列的植入；另一方面，在植入柔性神经电极之前，利用固定物把组 装后的柔性神经电极和辅助植入组件固定或连接在一起，省去了在植入时将柔性神经电极和辅助植入组件现场组装在一起的操作，提高了植入效率，缩短手术时间；另外，由于柔性神经电极和辅助植入组件为组装好的整体结构，便于运输和使用。
例如，步骤S100中，形成柔性神经电极1的方法有多种，例如光刻工艺、微机电系统(MEMS)等。
在一个示例中，多个柔性神经电极的制备方法包括如下步骤：
S101：清洗并且烘干基底。
例如，该基底为硅片，通过超声清洗并采用氮气吹干，再用等离子体进行清洗。
S102：在基底上形成多个凹槽，该多个凹槽对应于多个柔性神经电极1的多个植入部分10上的多个辅助结构11。
例如，辅助结构11可以为通孔、凹槽或凸起，通过设置多个凹槽，可方便在将辅助植入针20插入通孔时为穿过通孔的辅助植入端201提供容纳空间，利于电极的转移。
S103：在形成有多个凹槽的基底上形成牺牲层。
在组装柔性神经电极阵列和辅助植入组件时，通过在基底上形成牺牲层，有利于释放形成在基底上的柔性神经电极阵列。例如，牺牲层可采用聚甲基丙烯酸甲酯(polymethyl methacrylate，PMMA)、铝(Al)、镍(Ni)等中的一种或多种。本实施例中采用PMMA作为牺牲层，柔性神经电极阵列形成在牺牲层上。当柔性神经电极阵列部分浸泡到诸如丙酮的溶液中时，溶液没过PMMA牺牲层，待PMMA牺牲层彻底溶解，柔性神经电极阵列则从基底上被释放。
S104：在形成有牺牲层的基底上形成柔性神经电极阵列。
例如，柔性神经电极阵列包括多个柔性神经电极1，柔性神经电极1包括柔性绝缘层101和导电层102，其中导电层102包括多个导电线103；柔性神经电极1还包括植入部分1和位于植入部分1上的辅助结构11。通过去除部分柔性绝缘层101以使部分导电线103暴露以形成电极位点104。例如，导电层102可以采用光刻工艺形成。
本公开实施例中，光刻工艺包括但不限于，涂布光刻胶、利用掩模板曝 光、显影、刻蚀、剥离剩余光刻胶等。可以理解的是，导电层102可以仅一层，也可以有多层，每个导电层102可设置多个导电线103，并且相邻导电层102之间彼此绝缘。
图9为本公开实施例提供的柔性神经电极复合结构的制造方法中形成的柔性神经电极的结构示意图。图10为沿图9的AA线截取的截面示意图。
如图9和图10所示，硅片310中形成有圆形凹槽320，用于容纳穿过辅助结构11b的辅助植入针，圆形凹槽320的直径为60μm、深度为100μm。在形成有圆形凹槽320的硅片310上形成有PMMA牺牲层330。在PMMA牺牲层330上形成有柔性神经电极1b。其中，柔性神经电极1b包括具有盘旋结构的植入部分10b。植入部分10b包括辅助结构11b(如图中所示的通孔111b)和电极位点104b。柔性神经电极1b还包括导电线103b，该导电线103b与电极位点111b连接。
本公开实施例中，圆形凹槽直径可以为5～100μm，如5μm，10μm，20μm，25μm，30μm，40μm，50μm，100μm等，例如为40～60μm；圆形凹槽的深度可以为1-200μm，如0μm，5μm，10μm，15μm，25μm，30μm，40μm，50μm，100μm,150μm，200μm等，例如为100-150μm。牺牲层的厚度为0-20μm，如1μm，2μm，5μm，10μm，20μm等，例如为1μm。
例如，步骤S200可进一步包括：
S201：形成辅助固定件21；
S202：形成多个辅助植入针20；
S203：将辅助固定件21和多个辅助植入针20连接在一起。
图11至图13为本公开实施例提供的辅助植入组件的制作方法的截面示意图。例如，图11至图13示出了图6的辅助植入组件的制作过程，包括如下步骤：
1)选用直径为250μm的多个商品化光纤30，每个光纤30由直径为125μm的高纯度二氧化硅(SiO2)纤芯和外径为250μm的丙烯酸酯涂层组成。将光纤30用光纤切割刀切割成长度为大约1cm的光纤段，并用剥线钳剥离掉尖端大约50μm的丙烯酸酯涂层。
2)如图11所示，选用三个硅片2111～2113作为辅助固定板，并且在每个硅片上形成多个开孔212。例如，在硅片2111上利用激光进行刻蚀，以得 到3×4阵列方式排布的多个开孔212。3×4的开孔阵列方式与柔性神经电极阵列的3×4的通孔111的排列方式相同。开孔212的直径例如为260μm。然后，将多个光纤30插入到硅片2111～2113对应的12个开孔212中起到固定和准直的作用。硅片2111～2112起到准直多个光纤30的作用，硅片2113用于光纤30的位置固定。
3)如图12所示，将相邻两层硅片2111、2112之间以及光纤30和每个硅片2111、2112之间加入粘合剂22，例如环氧胶固定。如图13所示，将硅片2111的顶部用环氧胶固定在3D打印的底托中。
4)如图13所示，将光纤30的尖端用BOE(Buffered Oxide Etch)缓冲氧化物刻蚀液进行刻蚀。刻蚀过程如下：首先，将光纤30的尖端的125μm的纤芯刻蚀至直径大约60μm；然后，将光纤30从刻蚀液中取出并用去离子水清洗三遍，并将其浸入50℃的无水乙醇中浸泡，去除光纤30表面的丙烯酸酯涂层；最后，将去除丙烯酸酯涂层的光纤30继续用BOE缓冲氧化物刻蚀液刻蚀处理，得到尖端直径为大约20μm的光纤，最终得到图6所示的辅助植入组件。
上述制造方法中，也可以采用钨丝替代光纤30作为辅助植入针。在此情况下，上述步骤4)可替换为以下步骤4’):
将钨丝的前端大约6mm长度没入2mol/L的氢氧化钠(NaOH)溶液当中，采用辰华电化学工作站(CHI660)的恒电位模式进行电化学刻蚀，过电位5.0V，将钨丝的直径刻蚀到大约100μm；进而将钨丝尖端提起，只将钨丝大约2mm长度的尖端没入NaOH溶液中继续刻蚀，直到弯月面处断裂，刻蚀得到具有平头尖端的钨丝，最终同样得到图6所示的辅助植入组件。
例如，在步骤S300之前，上述制造方法还包括：
S500：将辅助植入端201对准辅助结构11。
例如，将多个辅助植入端201中的至少一个辅助植入端201对准多个辅助结构11中的至少一个辅助结构11，有利于更快速地将辅助植入端201与辅助结构11组装在一起。
例如，将辅助植入组件2用立体定位仪预固定，将柔性神经电极1的阵列至于旋转台上调整为辅助植入组件2对准，其中旋转台例如为可进行多角度旋转的多轴精密气浮转台。
例如，步骤S400可进一步包括：至少在辅助植入端201和辅助结构11的连接处形成固定物3，如图2和图3所示。例如，固定物3至少填充在辅助植入端201的尖端203与通孔111之间，以使尖端203与通孔111之间保持相对位置不变。进一步地，例如固定物3形成为膜，该膜将多个辅助植入端201和多个辅助结构11连接在一起。固定物3的具体材料可参考前面实施例的描述，此处不再赘述。
在一个示例中，当形成辅助植入组件和柔性神经电极阵列之后，进行以下步骤：
a)将形成有圆形凹槽320、PMMA牺牲层330和多个柔性神经电极1b(以下简称为柔性神经电极阵列)的硅片310置于多轴精密气浮转台上；
b)将图6中制备得到的辅助植入组件2的顶部固定在可三维移动的立体定位仪上；
c)调整立体定位仪，将辅助植入组件2降低逐渐接近柔性神经电极阵列表面，调整气浮转台的X、Y、Z轴，将多个辅助植入组件2的光纤30的尖端与柔性神经电极阵列中的多个通孔111b对齐；
d)继续将辅助植入组件2降低，直到多个光纤30的尖端插入到硅片310的多个圆形凹槽320中；
e)在光纤30的尖端与柔性神经电极阵列表面滴加5％PVA水溶液，待其中的水分蒸发后，柔性神经电极阵列与辅助植入组件2之间由PVA得到固定；
f)将柔性神经电极阵列部分浸泡入丙酮中进行释放，丙酮的量以没过PMMA牺牲层以上为准，待PMMA牺牲层彻底溶解，柔性神经电极阵列被释放，得到柔性神经电极阵列复合电极。
本公开至少一个实施例还提供一种复合结构组件，复合结构组件包括多个前述任一实施例描述的柔性神经电极复合结构。
图14为本公开实施例提供的复合结构组件的结构示意图。
如图14所示，复合结构组件40包括多个柔性神经电极复合结构410(例如图中所示三个)，每个柔性神经电极复合结构410具有与前面图1所示的柔性神经电极复合结构100相同的构造。
例如，复合结构组件40还包括具有多个导电线的连接部420。每个导电 线连接于柔性神经电极的电极位点与焊盘(未示出)之间，以实现信号传输。
本公开实施例提供的复合结构组件中，由于每个柔性神经电极复合结构利用固定物固定辅助植入端和辅助结构，从而将辅助植入组件和多个柔性神经电极固定在一起，这样在柔性神经电极植入过程中，可同时将多个柔性神经电极植入431。
到目标组织。相比于单根逐一的植入方法，一方面，缩短植入时间，降低植入难度，从而实现高通量、高覆盖率的柔性神经电极阵列的植入；另一方面，在植入柔性神经电极之前，利用固定物把组装后的柔性神经电极和辅助植入组件固定或连接在一起，省去了在植入时将柔性神经电极和辅助植入组件现场组装在一起的操作，提高了植入效率，缩短手术时间；另外，由于柔性神经电极和辅助植入组件为组装好的整体结构，便于运输和使用。
本公开至少一个实施例还提供一种采用前面任一实施例描述的柔性神经电极复合结构的柔性神经电极的植入方法。
图15为本公开实施例提供的采用图1的柔性神经电极复合结构的柔性神经电极的植入方法。
结合图1和图15，上述植入方法包括：
S1：移动柔性神经电极复合结构100，以带动多个柔性神经电极1的植入部分10移动到目标组织的表面；
S2：融解或溶解固定物3，以使辅助植入端201与辅助结构11处于可分离状态；
S3：向目标组织移动辅助植入组件2，以带动多个柔性神经电极1的多个植入部分10移动到目标组织；以及
S4：移去辅助植入组件2，并且将多个柔性神经电极1中的至少部分柔性神经电极留在所述目标组织处。
例如，在向目标组织移动辅助植入组件2时，多个柔性神经电极1的多个植入部分10同时移动到目标组织。在移去辅助植入组件2时，可将辅助植入组件提起，使辅助植入组件2与留在目标组织上的柔性神经电极1脱离，这样，辅助植入组件2可二次利用或直接丢弃。留在目标组织处的柔性神经电极可以是多个柔性神经电极1中的部分或全部。当全部柔性神经电极1都留在目标组织处时，可在目标组织上提供更多电极位点。
如图1所示，每个植入部分10为可拉伸的盘旋结构时，辅助结构11位于可拉伸的盘旋结构上。这样，在向目标组织移动辅助植入组件2以带动多个柔性神经电极1的多个植入部分10移动到目标组织时，可利用辅助植入端201向下推动辅助结构11，以使可拉伸的盘旋结构展开在z方向展开。
如图7所示，每个植入部分10a为直线形结构，辅助结构11a位于直线形结构上。这样，在向目标组织移动辅助植入组件2a以带动多个柔性神经电极1a的多个植入部分10a移动到目标组织时，可利用辅助植入端201a移动辅助结构11a，以带动直线形结构移动到目标组织。与图1所示的盘旋结构相比，图7中需要将柔性神经电极1a的后端随着前端的植入进行推动，或在植入之前，将柔性神经电极1a后端折叠预留一定的长度，从而为柔性神经电极的整体植入预留植入空间。
本公开实施例提供的柔性神经电极的植入方法中，可同时将多个柔性神经电极植入到目标组织。相比于单根逐一的植入方法，一方面，缩短植入时间，降低植入难度，从而实现高通量、高覆盖率的柔性神经电极阵列的植入；另一方面，在植入柔性神经电极之前，利用固定物把组装后的柔性神经电极和辅助植入组件固定或连接在一起，省去了在植入时将柔性神经电极和辅助植入组件现场组装在一起的操作，提高了植入效率，缩短手术时间；另外，由于柔性神经电极和辅助植入组件为组装好的整体结构，便于运输和使用。
在一个示例中，柔性神经电极的植入方法包括以下步骤：
(1)大鼠麻醉：取健康SPF级大鼠，按照0.01g/mL的标准注射戊巴比妥钠将大鼠麻醉；待大鼠深度麻醉之后，将其固定在立体定位仪上，并后续用小动物麻醉剂进行气体麻醉；用棉签蘸碘伏在大鼠头部涂抹消毒，并将毛发剪去；用剪刀将大鼠头皮沿中缝剪去，清理颅骨表面组织，露出干净颅骨。
(2)开颅窗：于大鼠前囟门前后2.5mm和中线左右3.5mm用颅钻钻出5mm×7mm的长方形颅窗，并小心挑去硬脑膜以提供用于植入柔性神经电极的位置。
(3)电极植入：将前面任一实施例制备的利用PVA膜固定的柔性神经电极复合结构固定在立体定位仪上，并将其逐渐靠近大鼠脑表颅窗内；待柔性神经电极阵列的PVA膜与脑表接触后，在PVA膜与硅片之间的空隙滴加生理盐水，溶解PVA膜；待PVA膜溶解后，柔性神经电极彻底释放后，开 始进行电极的植入，立体定位仪夹持杆下降速度大约20μm/s。待下降高度大约1mm，即光纤尖端接触脑表后计高度，继续下降夹持杆至植入深度为1.5mm后，停止植入；提起辅助植入组件，提起速度大约100μm/s，完成电极植入；最后，用隔离胶封闭颅骨孔，在电极周围和铁片底托之间涂抹牙科水泥进行固定。
本公开至少一个实施例还提供一种采用前面实施例中描述的复合结构组件的柔性神经电极的植入方法，包括：利用多个柔性神经电极复合结构将多组柔性神经电极植入到目标组织，每组柔性神经电极包括多个柔性神经电极。
参考图14，该植入方法包括利用多个柔性神经电极复合结构410分别将第一组柔性神经电极431、第二组柔性神经电极432和第三组柔性神经电极433依次植入到目标组织中，每组柔性神经电极例如包括12个柔性神经电极。可选地，还可以利用多个柔性神经电极复合结构410将第一组柔性神经电极431、第二组柔性神经电极432和第三组柔性神经电极433同时植入到目标组织中。通过上述方法，可以提高植入效率，缩短植入时间。
本公开至少一个实施例还提供一种辅助植入组件。例如，如图5所示，辅助植入组件2包括：辅助固定件21，辅助固定件21包括至少一个辅助固定板211；多个辅助植入针20，构造为与至少一个辅助固定板211连接，多个辅助植入针20的延伸方向(如图中所示z方向)与至少一个辅助固定板211所在的平面(如图中所示xy平面)不平行。
例如，至少一个辅助固定板211与多个辅助植入针20之间为可拆卸连接或固定连接。例如，至少一个辅助固定板211上设置有开孔212，多个辅助植入针20包括与辅助植入端201相对设置的固定端202，固定端202构造为穿过开孔212以与至少一个辅助固定板211连接。
例如，如图6所示，辅助植入组件2还包括：粘合剂22，至少部分粘合剂22位于至少一个辅助固定板和多个辅助植入针20之间。
利用本公开实施例提供的辅助植入组件，可以将植入式柔性神经电极阵列进行整体转移和植入，与单根逐一植入相比，阵列植入和转移的方法可以大大提高转移、释放和植入效率，降低植入时间耗时，为植入式柔性神经电极阵列的大范围植入提供简单、高效的方法。本公开实施例提供的植入方法中，其植入速度为1～200μm/s(微米/秒)，如1μm/s，5μm/s，10μm/s，15μm/s， 20μm/s，30μm/s，50μm/s，100μm/s，200μm/s，例如为10μm/s～20μm/s。
本文中，有以下几点需要注意：
(1)本公开实施例附图只涉及到与本公开实施例涉及到的结构，其他结构可参考通常设计。
(2)在不冲突的情况下，本公开的实施例及实施例中的特征可以相互组合以得到新的实施例。
以上所述仅是本公开的示范性实施方式，而非用于限制本公开的保护范围，本公开的保护范围由所附的权利要求确定。

Claims (38)

  1. 一种柔性神经电极复合结构，包括：
    多个柔性神经电极，每个所述柔性神经电极包括植入部分和设置于所述植入部分的辅助结构；
    辅助植入组件，包括与所述多个柔性神经电极一一对应的多个辅助植入针，每个所述辅助植入针包括位于靠近与其对应的柔性神经电极一端的辅助植入端，所述辅助植入端构造为与所述辅助结构组装；和
    固定物，构造为将组装的所述辅助植入端和所述辅助结构固定。
  2. 根据权利要求1所述的柔性神经电极复合结构，其中所述多个辅助植入针的延伸方向与所述多个柔性神经电极的多个植入部分的延伸方向不平行。
  3. 根据权利要求2所述的柔性神经电极复合结构，其中每个所述植入部分为直线形结构，所述多个辅助植入针的延伸方向与多个直线形结构的延伸方向不平行。
  4. 根据权利要求2所述的柔性神经电极复合结构，其中每个所述植入部分为可拉伸的盘旋结构，所述多个辅助植入针的延伸方向与所述多个盘旋结构所在的平面不平行。
  5. 根据权利要求4所述的柔性神经电极复合结构，其中所述辅助结构位于所述可拉伸的盘旋结构的端部处。
  6. 根据权利要求2所述的柔性神经电极复合结构，其中所述多个柔性神经电极包括多个植入部分，所述多个植入部分中的一部分为直线形结构，另一部分为可拉伸的盘旋结构。
  7. 根据权利要求2所述的柔性神经电极复合结构，其中所述多个辅助植入针的延伸方向与所述多个柔性神经电极的多个植入部分的延伸方向相互垂直。
  8. 根据权利要求1所述的柔性神经电极复合结构，其中所述辅助植入端和与所述辅助结构构造为通过插接方式组装在一起。
  9. 根据权利要求8所述的柔性神经电极复合结构，其中所述辅助植入端构造为部分或全部插入所述辅助结构中。
  10. 根据权利要求9所述的柔性神经电极复合结构，其中所述辅助结构为位于所述植入部分上的通孔、凹槽或凸起。
  11. 根据权利要求8所述的柔性神经电极复合结构，其中每个所述辅助植入针的截面形状包括三角形、长方形、圆形、椭圆形和正多边形中的一种。
  12. 根据权利要求8所述的柔性神经电极复合结构，其中每个所述辅助植入针的材料包括金属、合金和非金属中的一种或多种。
  13. 根据权利要求1所述的柔性神经电极复合结构，其中所述辅助植入组件还包括：
    辅助固定件，所述辅助固定件位于所述多个辅助植入针远离所述多个柔性神经电极的一侧并且构造为固定所述多个辅助植入针。
  14. 根据权利要求13所述的柔性神经电极复合结构，其中所述辅助固定件包括辅助固定板，所述辅助固定板所在平面与所述多个辅助植入针的延伸方向不平行。
  15. 根据权利要求14所述的柔性神经电极复合结构，其中所述辅助固定板所在平面与所述多个辅助植入针的延伸方向相互垂直。
  16. 根据权利要求14所述的柔性神经电极复合结构，其中所述辅助固定板与所述多个辅助植入针之间构造为可拆卸连接或固定连接。
  17. 根据权利要求16所述的柔性神经电极复合结构，其中所述辅助固定板上设置有多个开孔，所述多个辅助植入针包括沿其延伸方向远离所述辅助植入端的固定端，所述固定端构造为穿过所述多个开孔以与所述辅助固定板连接。
  18. 根据权利要求13所述的柔性神经电极复合结构，其中所述辅助植入组件还包括：
    粘合剂，至少部分所述粘合剂位于所述辅助固定板和所述多个辅助植入针之间并构造为将所述辅助固定板和所述多个辅助植入针相互粘结。
  19. 根据权利要求1所述的柔性神经电极复合结构，其中所述固定物的至少一部分位于所述辅助植入端和所述辅助结构之间以保持所述辅助植入端和所述辅助结构之间的相对位置。
  20. 根据权利要求19所述的柔性神经电极复合结构，其中所述固定物包括光融解材料、热融解材料、液体溶胀材料和液体溶解材料中的一种或多种。
  21. 根据权利要求20所述的柔性神经电极复合结构，其中所述液体溶解包括可被液体溶解的聚合物材料，所述聚合物材料包括聚乙烯醇、蚕丝蛋白、聚乙二醇和明胶中的一种或多种；所述液体包括超纯水、生理盐水和磷酸盐缓冲液中的一种或多种。
  22. 根据权利要求19所述的柔性神经电极复合结构，其中所述固定物采用膜的形式，所述膜将所述多个辅助植入端和所述多个辅助结构固定在一起。
  23. 根据权利要求22所述的柔性神经电极复合结构，其中所述膜至少将所述多个辅助植入端和所述多个辅助结构之间的多个连接处固定在一起。
  24. 一种柔性神经电极复合结构的制造方法，包括：
    提供多个柔性神经电极，每个所述柔性神经电极包括植入部分和形成于所述植入部分上的辅助结构；
    形成辅助植入组件，所述辅助植入组件包括多个辅助植入针，每个所述辅助植入针包括位于靠近所述多个柔性神经电极一侧的辅助植入端；
    组装所述辅助植入端与所述辅助结构；和
    固定组装的所述辅助植入端和所述辅助结构。
  25. 根据权利要求24所述的制造方法，其中，在将所述辅助植入端与所述辅助结构组装之前，所述制造方法还包括：将所述辅助植入端对准所述辅助结构。
  26. 根据权利要求25所述的制造方法，其中，将所述辅助植入端对准所述辅助结构包括：将多个所述辅助植入端中的至少一个辅助植入端对准多个所述辅助结构中的至少一个辅助结构。
  27. 根据权利要求24所述的制造方法，其中，所述固定组装的所述辅助植入端和所述辅助结构包括：
    至少在所述辅助植入端和所述辅助结构的连接处形成固定物。
  28. 一种采用权利要求1至23任一项所述的柔性神经电极复合结构的柔性神经电极的植入方法，包括：
    移动所述柔性神经电极复合结构，以带动所述多个柔性神经电极的植入部分移动到目标组织的表面；
    融解或溶解所述固定物，以使所述辅助植入端与所述辅助结构处于可分离状态；
    向所述目标组织移动所述辅助植入组件，以带动所述多个柔性神经电极的多个植入部分移动到所述目标组织；以及
    移去所述辅助植入组件，并且将所述多个柔性神经电极中的至少部分柔性神经电极留在所述目标组织处。
  29. 根据权利要求28所述的柔性神经电极的植入方法，其中，在向所述目标组织移动所述辅助植入组件时，所述多个柔性神经电极的多个植入部分同时移动到所述目标组织。
  30. 根据权利要求28所述的柔性神经电极的植入方法，其中，所述多个柔性神经电极包括多个植入部分，其中每个所述植入部分为可拉伸的盘旋结构，所述辅助结构位于所述可拉伸的盘旋结构上，
    所述向所述目标组织移动所述辅助植入组件以带动所述多个柔性神经电极的多个植入部分移动到所述目标组织，包括：
    利用所述辅助植入端移动所述辅助结构，以使所述可拉伸的盘旋结构展开。
  31. 根据权利要求28所述的柔性神经电极的植入方法，其中，所述多个柔性神经电极包括多个植入部分，其中每个所述植入部分为直线形结构，所述辅助结构位于所述直线形结构上，
    所述向所述目标组织移动所述辅助植入组件以带动所述多个柔性神经电极的多个植入部分移动到所述目标组织，包括：
    利用所述辅助植入端移动所述辅助结构，以带动所述直线形结构移动到所述目标组织。
  32. 一种复合结构组件，包括多个权利要求1至23任一项所述的柔性神经电极复合结构。
  33. 一种采用权利要求32所述的复合结构组件的柔性神经电极的植入方法，包括：利用所述多个柔性神经电极复合结构将多组柔性神经电极植入到目标组织，每组柔性神经电极包括多个柔性神经电极。
  34. 根据权利要求33所述的植入方法，其中，
    利用所述多个柔性神经电极复合结构将所述多组柔性神经电极同时植入到所述目标组织，或者
    利用所述多个柔性神经电极复合结构将所述多组柔性神经电极分别依次 植入到所述目标组织。
  35. 一种辅助植入组件，包括：
    辅助固定件，所述辅助固定件包括至少一个辅助固定板；
    多个辅助植入针，构造为与所述至少一个辅助固定板连接，所述多个辅助植入针的延伸方向与所述至少一个辅助固定板所在的平面不平行。
  36. 根据权利要求35所述的辅助植入组件，其中，所述至少一个辅助固定板与所述多个辅助植入针之间为可拆卸连接或固定连接。
  37. 根据权利要求36所述的辅助植入组件，其中，所述至少一个辅助固定板上设置有多个开孔，所述多个辅助植入针包括与所述辅助植入端相对设置的固定端，所述固定端构造为穿过所述开孔以与所述至少一个辅助固定板连接。
  38. 根据权利要求35所述的辅助植入组件，其中，所述辅助植入组件还包括：
    粘合剂，至少部分所述粘合剂位于所述至少一个辅助固定板和所述多个辅助植入针之间。
PCT/CN2023/085296 2022-04-02 2023-03-31 柔性神经电极复合结构及制造、植入方法和辅助植入组件 WO2023186053A1 (zh)

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