Flexible neural electrode composite structures and methods of manufacture, implantation and auxiliary implantation assemblies

Abstract

The embodiments of the present disclosure provide a flexible neural electrode composite structure and a manufacturing method, an implantation method and an auxiliary implantation assembly. The flexible neural electrode composite structure comprises: a plurality of flexible neural electrodes, each of the flexible neural electrodes comprising an implantation part and an auxiliary structure arranged on the implantation part; an auxiliary implantation assembly comprising a plurality of auxiliary implantation needles corresponding to the plurality of flexible neural electrodes one by one, each of the auxiliary implantation needles comprising an auxiliary implantation end located close to one end of the flexible neural electrode corresponding thereto, the auxiliary implantation end being configured to be assembled with the auxiliary structure; and a fixing object configured to fix the assembled auxiliary implantation end and the auxiliary structure.

Description

TECHNICAL FIELD

[0001] The present disclosure relates to the technical field of neuroscience, and in particular, to a flexible neural electrode composite structure and a manufacturing method and an implantation method thereof, a composite structure assembly and an implantation method thereof, and an auxiliary implantation assembly. BACKGROUND

[0002] In recent years, implantable neural electrodes have been rapidly developed as an important tool for brain function analysis, brain disease treatment, and brain-computer interface. However, since traditional implantable neural electrodes are rigid, they do not match the mechanical properties of brain tissue. After being implanted into the brain, the two will move relative to each other under the influence of breathing and movement, thereby causing great damage to the brain tissue around the electrode and further triggering an inflammatory response. When the immune proliferative cells wrap around the electrode surface, the brain electrode recording signal will continuously weaken until failure.

[0003] Compared with rigid neural electrodes, flexible neural electrodes have more matched mechanical properties with neural tissue, which can reduce the immune damage to brain tissue, thereby improving the stability of neural signal detection and enabling long-time recording of brain electrical signals. However, how to achieve high-throughput and large-range implantation of flexible neural electrodes in the brain (and other neural tissues) is a problem to be solved at present. SUMMARY

[0004] Embodiments of the present disclosure provide a flexible neural electrode composite structure and a manufacturing method and an implantation method thereof, a composite structure assembly and an implantation method thereof, and an auxiliary implantation assembly.

[0005] According to a first aspect of the present disclosure, a flexible neural electrode composite structure is provided, comprising: a plurality of flexible neural electrodes, each of the flexible neural electrodes comprising an implantation part and an auxiliary structure arranged on the implantation part; an auxiliary implantation assembly comprising a plurality of auxiliary implantation needles corresponding one-to-one to the plurality of flexible neural electrodes, each of the auxiliary implantation needles comprising an auxiliary implantation end located close to one end of the flexible neural electrode corresponding thereto, the auxiliary implantation end being configured to be assembled with the auxiliary structure; and a fixing object configured to fix the assembled auxiliary implantation end and the auxiliary structure.

[0006] According to a second aspect of the present disclosure, a manufacturing method of a flexible neural electrode composite structure is provided, comprising: providing a plurality of flexible neural electrodes, each of the flexible neural electrodes comprising an implantation part and an auxiliary structure formed on the implantation part; forming an auxiliary implantation assembly, the auxiliary implantation assembly comprising a plurality of auxiliary implantation needles, each of the auxiliary implantation needles comprising an auxiliary implantation end located close to one side of the plurality of flexible neural electrodes; assembling the auxiliary implantation end with the auxiliary structure; and fixing the assembled auxiliary implantation end and the auxiliary structure.

[0007] According to a third aspect of this disclosure, a method for implanting a flexible neural electrode using the aforementioned flexible neural electrode composite structure is provided, comprising: moving the flexible neural electrode composite structure to move the implantation portions of the plurality of flexible neural electrodes to the surface of a target tissue; melting or dissolving the fixation material to make the auxiliary implantation end separable from the auxiliary structure; moving the auxiliary implantation assembly toward the target tissue to move the plurality of implantation portions of the plurality of flexible neural electrodes to the target tissue; and removing the auxiliary implantation assembly, leaving the plurality of flexible neural electrodes at the target tissue.

[0008] According to a fourth aspect of this disclosure, a composite structure component is provided, including the aforementioned flexible neural electrode composite structure.

[0009] According to a fifth aspect of this disclosure, a method for implanting a flexible neural electrode using the aforementioned composite structure component is provided, comprising: implanting multiple sets of flexible neural electrodes into a target tissue using the multiple flexible neural electrode composite structure, wherein each set of flexible neural electrodes includes multiple flexible neural electrodes.

[0010] According to a sixth aspect of this disclosure, an auxiliary implantation assembly is provided, comprising: an auxiliary fixation member, the auxiliary fixation member including at least one auxiliary fixation plate; and a plurality of auxiliary implantation needles configured to be connected to the at least one auxiliary fixation plate, wherein the extension direction of the plurality of auxiliary implantation needles is not parallel to the plane in which the at least one auxiliary fixation plate is located. Attached Figure Description

[0011] To more clearly illustrate the technical solutions of the embodiments of this disclosure, the accompanying drawings of the embodiments will be briefly described below. Obviously, the drawings described below only relate to some embodiments of this disclosure and are not intended to limit this disclosure.

[0012] Figure 1 This is a three-dimensional schematic diagram of the flexible neural electrode composite structure provided in the embodiments of this disclosure.

[0013] Figure 2 for Figure 1 A schematic diagram of the cross-section of the flexible neural electrode composite structure taken along the dashed plane a.

[0014] Figure 3 for Figure 2 A partially enlarged schematic diagram of the flexible neural electrode composite structure.

[0015] Figure 4A for Figure 1 A schematic diagram of the local three-dimensional structure of region b of the flexible neural electrode composite structure.

[0016] Figure 4B for Figure 1a top view of a flexible neural electrode array.

[0017] Figure 5 A structural schematic diagram of an auxiliary implant assembly provided by an embodiment of the present disclosure.

[0018] Figure 6 A cross-sectional schematic diagram of an auxiliary implant assembly of another embodiment of the present disclosure.

[0019] Figure 7 A structural schematic diagram of a flexible neural electrode composite structure provided by another embodiment of the present disclosure.

[0020] Figure 8 A flowchart of a manufacturing method of a flexible neural electrode composite structure provided by an embodiment of the present disclosure.

[0021] Figure 9 A structural schematic diagram of a flexible neural electrode formed in a manufacturing method of a flexible neural electrode composite structure provided by an embodiment of the present disclosure.

[0022] Figure 10 A cross-sectional schematic diagram taken along an AA line of Figure 9 .

[0023] Figures 11 to 13 A cross-sectional schematic diagram of a manufacturing method of an auxiliary implant assembly provided by an embodiment of the present disclosure.

[0024] Figure 14 A structural schematic diagram of a composite structure assembly provided by an embodiment of the present disclosure.

[0025] Figure 15 An implantation method of a flexible neural electrode of a flexible neural electrode composite structure provided by an embodiment of the present disclosure. Figure 1 DETAILED DESCRIPTION

[0026] In order to make the purposes, technical solutions, and advantages of the embodiments of the present disclosure clearer, the technical solutions of the embodiments of the present disclosure will be described clearly and completely below with reference to the drawings of the embodiments of the present disclosure. Obviously, the described embodiments are some but not all of the embodiments of the present disclosure. Based on the described embodiments of the present disclosure, all other embodiments obtained by those of ordinary skill in the art without creative effort belong to the scope of protection of the present disclosure.

[0027] ​Unless otherwise defined, technical terms or scientific terms used herein shall have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. The use of the terms "first", "second", and the like do not imply any order, quantity, or importance, but are used to distinguish one element from another. The terms "include", "comprise", and the like are used synonymously with the term "comprising" and are intended not to exclude, but to include, whatever falls within scope of the stated formula or integers. The terms "connected", "coupled", and the like are not restricted to direct connections or couplings, but can include indirect connections or couplings through an intermediary. The terms "upper", "lower", "left", "right", and the like are used to indicate relative positions, and can change according to an absolute position of the described object.

[0028] To stably combine with neural tissue closely at a large spatial scale, it is necessary to prepare a flexible neural electrode array with high throughput and high coverage. However, the implantation process of the current flexible neural electrode is limited by a lengthy implantation operation and a limited electrode implantation area. For example, when a single flexible neural electrode array is implanted one by one, not only is it time-consuming and labor-intensive, but also it is easy to cause intraoperative and postoperative complications due to a long craniotomy time during the operation.

[0029] To this end, the embodiments of the present disclosure provide a flexible neural electrode composite structure and a manufacturing method and an implantation method thereof, a composite structure assembly and an implantation method thereof, and an auxiliary implantation assembly, which realize high-throughput implantation by using a flexible neural electrode composite structure with an auxiliary implantation assembly, reduce the difficulty of implantation, and shorten the operation time.

[0030] At least one embodiment of the present disclosure provides a flexible neural electrode composite structure, comprising: a plurality of flexible neural electrodes, each of which comprises an implantation part and an auxiliary structure arranged on the implantation part; an auxiliary implantation assembly comprising a plurality of auxiliary implantation needles corresponding to the plurality of flexible neural electrodes one by one, each of which comprises an auxiliary implantation end located near one end of the corresponding flexible neural electrode, the auxiliary implantation end being configured to be assembled with the auxiliary structure; and a fixing object configured to fix the assembled auxiliary implantation end and auxiliary structure.

[0031] In the flexible neural electrode composite structure provided in this disclosure, a fixator is used to fix the auxiliary implantation end and the auxiliary structure, thereby fixing the auxiliary implantation component and multiple flexible neural electrodes together. This allows multiple flexible neural electrodes to be implanted into the target tissue simultaneously during the implantation process. Compared to the method of implanting one electrode at a time, this approach shortens implantation time and reduces implantation difficulty, enabling the implantation of high-throughput, high-coverage flexible neural electrode arrays. Furthermore, by fixing or connecting the assembled flexible neural electrodes and the auxiliary implantation component together with a fixator before implantation, the need for on-site assembly during implantation is eliminated, improving implantation efficiency and shortening surgical time. Additionally, since the flexible neural electrodes and the auxiliary implantation component are pre-assembled as a single structure, they are easy to transport and use. In this disclosure, "multiple" refers to two or more.

[0032] In this embodiment of the disclosure, multiple flexible neural electrodes can be arranged in one or more rows to form a flexible neural electrode array. Multiple auxiliary implantation needles can also be arranged in one or more rows to form an auxiliary implantation needle array. For example, the auxiliary implantation needle array can be an array of optical fibers, tungsten wires, platinum-iridium alloy wires, or nickel-chromium alloy wires arranged in three-dimensional space; or a silicon needle array fabricated using a micro-electro-mechanical system (MEMS); or a comb-shaped array obtained through deep silicon etching; or a needle-shaped array obtained through MEMS processing.

[0033] The present disclosure will now be described through several specific embodiments. To keep the following description of the embodiments of the present disclosure clear and concise, detailed descriptions of known functions and components may be omitted. When any component of an embodiment of the present disclosure appears in more than one drawing, the component may be represented by the same reference numerals in each drawing.

[0034] Figure 1 This is a three-dimensional schematic diagram of the flexible neural electrode composite structure provided in the embodiments of this disclosure.

[0035] like Figure 1 As shown, the flexible neural electrode composite structure 100 includes multiple flexible neural electrodes 1 (i.e., a flexible neural electrode array), an auxiliary implantation component 2, and a fixation device 3.

[0036] For example, each flexible neural electrode 1 includes an implantation portion 10 and an auxiliary structure 11 disposed on the implantation portion 10. The implantation portion 10 is configured to be implanted into a target tissue, such as the brain tissue of a human or animal, under the action of external force.

[0037] Figure 2 for Figure 1 A schematic diagram of the cross-section of the flexible neural electrode composite structure taken along the dashed plane a.Figure 3 For Figure 2 A partial enlarged view of the flexible neural electrode composite structure.

[0038] As Figure 3 shown, 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. For example, the conductive layer 102 includes a plurality of conductive wires 103. The plurality of conductive wires 103 are insulated from each other by the flexible insulating layer 101. As shown in FIG. 4, a plurality of electrode sites 104 are provided on the implanted portion 10, which are connected to the plurality of conductive wires 103 one by one for neural recording or regulation. The more the number of conductive wires 103, the more the electrode sites 104 of the flexible neural electrode 1, and the larger the range of signal recording. In one example, the electrode sites 104 are formed by removing part of the flexible insulating layer 101 to expose the conductive wires 103.

[0039] Figure 3 And Figure 4A each implanted portion 10 is shown to have only 10 electrode sites 104 and 10 conductive wires 103 connected thereto, it can be understood that the number of electrode sites 104 and the number of conductive wires 103 of each implanted portion 10 in other embodiments of the present disclosure can be determined according to actual needs, and the embodiments of the present disclosure are not limited in this regard.

[0040] In embodiments of the present disclosure, the arrangement of the plurality of implanted portions 10 of the plurality of flexible neural electrodes 1 can be various. Figure 4B For Figure 1 a top view of the plurality of flexible neural electrodes. As Figure 4B shown, the plurality of implanted portions 10 are arranged in the form of a 4x3 array, however, embodiments of the present disclosure are not limited thereto, and the plurality of implanted structures 10 can also be arranged in m rows and n columns, where m is greater than or equal to 1, and n is greater than or equal to 1.

[0041] Figure 4B In the flexible neural electrode array of

[0042] As Figure 2 and Figure 3As shown, the implantation portion 10 is provided with an auxiliary structure 11, which is configured to connect with the auxiliary implantation component 2. For example, the auxiliary structure 11 and the auxiliary implantation component 2 are interconnected by a plug-in connection.

[0043] like Figure 1 As shown, the auxiliary implantation component 2 includes, for example, a plurality of auxiliary implantation needles 20 corresponding one-to-one with a plurality of flexible neural electrodes 1. Each auxiliary implantation needle 20 includes an auxiliary implantation end 201 and a fixed end 202, wherein the auxiliary implantation end 201 is located at one end of the auxiliary implantation needle 20 closer to the flexible neural electrode 1, and the fixed end 202 is located at the other end of the auxiliary implantation needle 20 away from the flexible neural electrode 1. The auxiliary implantation end 201 is configured to be assembled with the auxiliary structure 11, so that the flexible neural electrode 1 and the auxiliary implantation component 2 can be assembled together.

[0044] In this embodiment, multiple flexible neural electrodes 1 are connected to the auxiliary implantation component 2 using the assembled auxiliary implantation end 201 and auxiliary structure 11, which facilitates the batch implantation of multiple flexible neural electrodes 1 through the auxiliary implantation component 2, thereby achieving high-throughput and high-coverage electrode implantation.

[0045] In this embodiment of the present disclosure, the extension directions of the plurality of auxiliary implantation needles 20 are not parallel to the extension directions of the plurality of implantation portions 10 of the plurality of flexible neural electrodes 1. In other words, the extension directions of the plurality of auxiliary implantation needles 20 and the extension directions of the plurality of implantation portions 10 of the plurality of flexible neural electrodes 1 spatially intersect, that is, they may or may not intersect.

[0046] For example, such as Figure 1 and Figure 2 As shown, multiple auxiliary implantation needles 20 extend parallel to each other along the z-direction. The implantation portion 10 of each flexible neural electrode 1 is, for example, a stretchable spiral structure, with the plane of the spiral structure being the xy-plane. The extension direction z of the auxiliary implantation needles 20 is not parallel to the xy-plane of the spiral structure; for example, they are perpendicular to each other. Thus, when implanting the flexible neural electrode, by making the extension directions of the multiple auxiliary implantation needles 20 perpendicular to the extension directions of the multiple implantation portions 10 of the multiple flexible neural electrodes 1, it is beneficial to control the implantation depth of the flexible neural electrode, thereby enabling the flexible neural electrode to reach the target tissue.

[0047] Figure 1 and Figure 2Only the case that the extension direction of the auxiliary implant needle 20 is perpendicular to the extension direction of the implanting part 10 of the flexible neural electrode is shown, and it can be understood that in other embodiments of the present disclosure, the extension direction of the auxiliary implant needle 20 can have a certain inclination angle relative to the xy plane where the spiral structure is located, for example, greater than 0 degrees and less than or equal to 90 degrees, which is also beneficial to control the implanting depth of the flexible neural electrode, and thus the embodiments of the present disclosure do not limit this.

[0048] As shown in Figure 1 and Figure 4A , when the implanting part 10 of each flexible neural electrode 1 is a stretchable spiral structure, it is beneficial to use the auxiliary implant assembly 2 to deploy the spiral structure during the implantation of the flexible neural electrode 1, so as to flexibly adjust the implanting depth of the flexible neural electrode 1 and further reduce the implanting difficulty.

[0049] In the embodiments of the present disclosure, ignoring the thickness of the spiral structure in the z direction, the spiral structure can be a two-dimensional planar structure as shown in Figure 1 , and can also be a three-dimensional structure, that is, a three-dimensional shape in the z direction, and the present disclosure does not limit this. Further, when the spiral structure is a two-dimensional planar structure as shown in Figure 1 , the spiral structure has, for example, a circular shape, a triangular shape, a quadrilateral shape, a polygonal shape, or a rounded triangular shape, a rounded quadrilateral shape, a rounded polygonal shape, and the like, and preferably, the spiral structure has a circular shape, which can be formed into a semicircle (i.e., 1 / 2 circle), 2 / 3 circle, or at least one circle, and the like. Those skilled in the art can determine the number of turns of the spiral structure according to the actual needs of the implanting depth, and the embodiments of the present disclosure do not limit this. When the number of turns increases, the implanting depth or length can be increased.

[0050] In the embodiments of the present disclosure, the auxiliary structure 11 is located at the end of the spiral structure, that is, the end of the implanting part 10, which is beneficial to more easily pull or stretch the spiral structure to deploy during the implantation of the flexible neural electrode. It can be understood that in other embodiments of the present disclosure, the auxiliary structure 11 can also be located at other positions of the end of the implanting part 10 (for example, the C1 position between the two electrode sites 104 of Figure 4A ) or at a part of the implanting part 10 away from the end (for example, the C2 position of Figure 4A ), which can also elongate or deploy the flexible neural electrode, and thus the embodiments of the present disclosure do not limit the position of the auxiliary structure 11.

[0051] Figure 1 and Figure 2Only the implanting part 10 is shown as a stretchable spiral structure, and it can be understood that the implanting part 10 can also have other shapes, such as a straight line structure or a wave structure, in other embodiments of the present disclosure. For example, the implanting part 10 can be one or more of a spiral structure, a wave structure, and a straight line structure.

[0052] In embodiments of the present disclosure, the auxiliary implanting end 201 and the auxiliary structure 11 are detachably assembled together, for example, assembled together by plugging, so as to facilitate installation and disassembly.

[0053] For example, as shown in Figure 2 , the auxiliary implanting 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 implanting part 10. In order to facilitate insertion into the through hole 111, the auxiliary implanting end 201 includes a pointed end 203, which has a diameter less than or equal to that of the auxiliary implanting needle 20.

[0054] For example, the pointed end 203 has a cross section that gradually decreases towards the auxiliary structure 11, such as the taper shown in the figure, which can be a circular cone or a pyramid. In this way, when assembling the auxiliary implanting end 201 and the auxiliary structure 11, the pointed end 203 can play a guiding role, facilitating quick insertion and assembly of the auxiliary structure 11. The pointed end 203 can also be flat, and embodiments of the present disclosure do not make specific limitations on the shape of the pointed end 203.

[0055] Figure 4A Only the case where the auxiliary structure 11 is a through hole is shown, and in other embodiments of the present disclosure, the auxiliary structure 11 can also be a groove or a protrusion, as long as it is a structure that can be plugged with the auxiliary implanting end 201, which is included in embodiments of the present disclosure.

[0056] In embodiments of the present disclosure, the auxiliary implanting end 201 is partially or entirely inserted into the auxiliary structure 11. For example, when the auxiliary implanting end 201 is entirely inserted into the auxiliary structure 11, the firmness after assembly can be improved; when the auxiliary implanting end 201 is partially inserted into the auxiliary structure 11, it is convenient to separate the flexible neural electrode 1 and the auxiliary implanting assembly 2 after implanting the flexible neural electrode 1. As shown in Figure 3 , the auxiliary implanting end 201 is partially inserted into the through hole 111, that is, the pointed end 203 is inserted into the through hole 111.

[0057] In embodiments of the present disclosure, the cross-sectional shape of each auxiliary implanting needle 20 includes one of a triangle, a rectangle, a circle, an ellipse, and a regular polygon. The cross-sectional shape of the auxiliary implanting needle 20 refers to Figure 1 the cross-sectional shape of the auxiliary implanting needle 20 in the xy plane, and when the cross-sectional shape is a circle or an ellipse, the damage to the brain tissue can be reduced, and thus it is preferred.

[0058] In this embodiment of the disclosure, each auxiliary implantation needle 20 is made of one or more of metals, alloys, and non-metals. Metals include, for example, tungsten. Non-metals include, for example, silicon or silicon dioxide. Alloys include, for example, platinum-iridium alloys or nickel-chromium alloys.

[0059] For example, the auxiliary implantation needle 20 can be a rigid microfilament, fabricated using optical fiber or tungsten wire with good collimation; or a silicon-based needle array obtained by deep silicon etching using microelectromechanical systems (MEMS); or a high aspect ratio SU-8 needle array structure fabricated using MEMS technology. Furthermore, when optical fiber or tungsten wire is used, it not only has high strength but also good collimation.

[0060] In this embodiment of the disclosure, when the cross-sectional shape of the auxiliary implantation needle 20 is circular, the diameter of the auxiliary implantation needle 20 ( Figure 3 The diameter D shown is 5–200 μm, for example, it can be 5 μm, 10 μm, 50 μm, 100 μm, 150 μm, or 200 μm. The larger the diameter D, the greater the damage to brain tissue. In one example, the diameter D is 50–150 μm, for example, it can be 50 μm, 75 μm, 100 μm, 125 μm, or 150 μm; further, for example, it is 75–100 μm. The auxiliary implantation needle 20 is, for example, manufactured by an etching process.

[0061] In this embodiment of the disclosure, the maximum diameter d of the tip of the auxiliary implantation needle 20 is 1 to 100 μm, for example, it can be 1 μm, 10 μm, 50 μm, or 100 μm. In one example, the maximum diameter d is 10 to 100 μm, such as 10 μm, 20 μm, 50 μm, or 100 μm; further, for example, it is 20 to 50 μm.

[0062] In this embodiment of the disclosure, the greater the difference in diameter between the tip 203 of the auxiliary implantation needle 20 and the auxiliary implantation needle 201, the better, for example, the difference in diameter between the two is 20 to 50 μm.

[0063] In this embodiment, the diameter of the through hole 111 is 1–100 μm, for example, it can be 1 μm, 10 μm, 50 μm, or 100 μm. In one example, the diameter of the through hole 111 is 5–100 μm, such as 5 μm, 10 μm, 20 μm, 50 μm, or 100 μm; further, for example, it is 20–50 μm. In this embodiment, in order to ensure the fit 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 implantation needle.

[0064] like Figures 1 to 3As shown, the fixing object 3 is configured to fix the assembled auxiliary implant end 201 and the auxiliary structure 11. For example, at least a portion of the fixing object 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, so as to ensure that the flexible neural electrode 1 and the auxiliary implant assembly 3 do not move relative to each other during transportation. Moreover, before implanting the flexible neural electrode, the fixing object 3 is used to fix or connect the assembled flexible neural electrode 1 and the auxiliary implant assembly 3 together, which eliminates the operation of assembling the flexible neural electrode 1 and the auxiliary implant assembly 3 on site during implantation, improves the implantation efficiency, and shortens the operation time. In addition, since the flexible neural electrode 1 and the auxiliary implant assembly 3 are an assembled whole structure, they are convenient to transport and use.

[0065] In the embodiments of the present disclosure, the fixing object 3 is configured to change its physical state with the change of external conditions. For example, at least one physical parameter used to characterize the physical state, such as volume, changes with the change of external conditions. In one example, the fixing object 3 changes from a solid state to a liquid state when the light or the ambient temperature changes, so that the volume changes. In another example, when a specific liquid is dropped on the fixing object 3, the fixing object 3 remains unchanged in the solid state, but the volume changes from small to large (i.e., swelling phenomenon occurs). When the physical state of the fixing object 3 changes, the auxiliary implant assembly 2 and the flexible neural electrode 1 are no longer bound together by the fixing object 3, and the two are in a separable state, which facilitates the subsequent operation of implanting the flexible neural electrode.

[0066] In the embodiments of the present disclosure, the fixing object 3 includes one or more of a light-melting material, a heat-melting material, a liquid-swelling material, and a liquid-dissolving material.

[0067] For example, the light-melting material includes a positive photosensitive resin, such as a diazo photosensitive resin, which works as follows: after the photosensitive film is exposed to light, the exposed part is decomposed and denitrated, and through a molecular rearrangement reaction, it becomes acid when it encounters water.

[0068] For example, the heat-melting material includes a heat-melting polymer, such as one or more of polyethylene glycol (PEG) and polylactic acid-glycolic acid copolymer-polyethylene glycol (PLGA-PEG).

[0069] For example, the liquid swelling material includes a water swelling polymer, such as one or more of poly(ethylene glycol) alginate diacrylate (PEGDA) and polyacrylamide-alginate (PAAm).

[0070] For example, the liquid dissolving material includes a water dissolving polymer, such as one or more of polyvinyl alcohol (PVA), silk fibroin, polyethylene glycol (PEG), poly(lactic-co-glycolic acid)-polyethylene glycol (PLGA-PEG), and gelatin; and the liquid includes one or more of ultrapure water, normal saline, and phosphate buffered saline (PBS). When the PVA solution is selected, the concentration of the PVA solution is 2% to 10%, such as 2%, 5%, 10%, and the like, for example, 5%.

[0071] As shown in Figures 1 to 3 The fixing material 3 is in the form of a film, for example, which fixes the plurality of auxiliary implant ends 201 and the plurality of auxiliary structures 11 together. In this way, the forming process of the fixing material 3 can be simplified, i.e., the plurality of auxiliary implant ends 201 and the plurality of auxiliary structures 11 are fixed together by a one-time film forming process. For example, the film at least fixes the plurality of connection portions of the plurality of auxiliary implant ends 201 and the plurality of auxiliary structures 11 together. In this way, the amount of fixing material can be reduced, and the impact on the target tissue due to the large amount of fixing material can be reduced. For example, the thickness of the film is greater than the width of the connection portion in the z direction, such as 30-50 μm.

[0072] As shown in Figure 1 and Figure 2 The auxiliary implant assembly 2 further includes an auxiliary fixing member 21, which is located on the side of the plurality of auxiliary implant needles 20 away from the plurality of flexible neural electrodes 1 and is configured to fix the plurality of auxiliary implant needles 20. By providing the auxiliary fixing member 21, the plurality of flexible neural electrodes 1 can be connected to the same object, so that when implanted, the doctor can move or implant the plurality of flexible neural electrodes 1 as a whole by grabbing the auxiliary fixing member.

[0073] Figure 5 A structural schematic diagram of an auxiliary implant assembly provided by an embodiment of the present disclosure.

[0074] As shown in Figure 5As shown, for example, the auxiliary fixing member 21 includes two auxiliary fixing plates 211, the plane where the auxiliary fixing plates 211 are located is the xy plane, and the extension direction of the plurality of auxiliary implant needles 20 is the z direction, so the xy plane where the auxiliary fixing plates 211 are located is perpendicular to the extension direction z of the plurality of auxiliary implant needles 20. By setting the plane where the auxiliary fixing plates 211 are located and the extension direction of the plurality of auxiliary implant needles 20 to be perpendicular to each other, it is beneficial to facilitate the control of the implantation depth of the flexible neural electrode in the process of implanting the flexible neural electrode.

[0075] Figure 5 Only the case where the plane where the auxiliary fixing plates 211 are located is perpendicular to the extension direction of the plurality of auxiliary implant needles 20 is shown, and it can be understood that in other embodiments of the present disclosure, the extension direction of the plurality of auxiliary implant needles 20 can not be parallel to the xy plane where the auxiliary fixing plates 211 are located, for example, the extension direction of the plurality of auxiliary implant needles 20 has a certain inclination angle relative to the xy plane, for example, the inclination angle is greater than 0 degrees and less than or equal to 90 degrees, which is also beneficial to control the implantation depth of the flexible neural electrode, so embodiments of the present disclosure do not limit this.

[0076] For example, the auxiliary fixing plates 211 and the plurality of auxiliary implant needles 20 are detachably connected or fixedly connected. When detachable connection is adopted, the number and position of the auxiliary implant needles 20 fixed to the auxiliary fixing plates 211 can be selected according to actual needs. When fixed connection is adopted, the stability of the entire flexible neural electrode composite structure can be improved.

[0077] Figure 6 A cross-sectional view of an auxiliary implant assembly according to another embodiment of the present disclosure is shown.

[0078] As shown in Figure 6 The auxiliary fixing plates 211 are provided with openings 212, and the plurality of auxiliary implant needles 20 include fixed ends 202 away from the auxiliary implant ends 201 along the extension direction thereof, and the fixed ends 202 are configured to pass through the openings 212 to be connected with the auxiliary fixing plates 211. By providing the openings 212 on the auxiliary fixing plates 211, detachable connection between the auxiliary implant needles 20 and the auxiliary fixing plates 211 can be achieved.

[0079] As shown in Figure 6 The auxiliary implant assembly 2 further includes an adhesive 22, and at least part of the adhesive 22 is located between the auxiliary fixing plates 211 and the plurality of auxiliary implant needles 20 and bonds the auxiliary fixing plates 211 and the plurality of auxiliary implant needles 20 to each other. By providing the adhesive 22, the firmness between the auxiliary fixing plates 211 and the plurality of auxiliary implant needles 20 can be improved, and the falling off or deviation of the auxiliary implant needles 20 during movement of the flexible neural electrode composite structure can be avoided, thereby affecting the implantation effect.

[0080] Figure 6In the embodiment shown in FIG. 2, two auxiliary fixation plates 211 are provided. It should be understood that the number of auxiliary fixation plates 211 can be one or more than two, and the present disclosure does not limit the number of auxiliary fixation plates 211. In the embodiment, two auxiliary fixation plates 211 with gaps are used to further ensure the collimation of the auxiliary implant needles and to further improve the firmness between the auxiliary fixation plates 211 and the plurality of auxiliary implant needles 20.

[0081] In the embodiment of the present disclosure, the plurality of auxiliary implant needles 20 can be arranged in various ways. For example, Figure 5 In the embodiment shown in FIG. 2, the plurality of auxiliary implant needles 20 are arranged in an array. However, in other embodiments, the arrangement of the plurality of auxiliary implant needles 20 can be determined by the arrangement of the plurality of flexible neural electrodes. For example, when the plurality of flexible neural electrodes are arranged in a circular, square, or polygonal shape, the plurality of auxiliary implant needles are also arranged in a circular, square, or polygonal shape to correspond one-to-one with the plurality of flexible neural electrodes 1.

[0082] Figure 7 FIG. 3 shows a structural schematic diagram of a flexible neural electrode composite structure according to another embodiment of the present disclosure. As shown in FIG. 3, the flexible neural electrode composite structure 100a includes four flexible neural electrodes 1a, an auxiliary implant assembly 2a, and a fixation (not shown). The four flexible neural electrodes 1a are arranged in a 2x2 array. Figure 7 For example, each flexible neural electrode 1a includes an implant portion 10a and an auxiliary structure 11a disposed on the implant portion 10a. The implant portion 10a is configured to be implanted into a target tissue under the action of an external force. The specific structure of the implant portion 10a of the flexible neural electrode 1a can refer to the description of the previous embodiments, which will not be repeated here.

[0083] As shown in FIG. 3, the implant portion 10a is provided with eight electrode sites 104a, and the eight electrode sites 104a are connected one-to-one with eight conductive wires 103a for neural recording or regulation.

[0084] In the embodiment shown in FIG. 1, the electrode sites 104 are located on one side of the implant portion 10 compared to Figure 7 In the embodiment shown in FIG. 3, the electrode sites 104a are distributed on both sides of the implant portion 10a, which can increase the number of electrode sites in a unit area, thereby recording or regulating more signals. Figure 4A Figure 7 As shown in FIG. 3, the implant portion 10a is provided with eight electrode sites 104a, and the eight electrode sites 104a are connected one-to-one with eight conductive wires 103a for neural recording or regulation.

[0085] As shown in FIG. 3, the implant portion 10a is provided with eight electrode sites 104a, and the eight electrode sites 104a are connected one-to-one with eight conductive wires 103a for neural recording or regulation. Figure 7 ​As shown, each implanting portion 10a is a linear structure, the extension direction of the plurality of auxiliary implanting needles 20 is the z direction, the extension direction of the plurality of linear structures is the x direction, and thus the extension direction of the plurality of auxiliary implanting needles 20a is perpendicular to the extension direction of the plurality of linear structures. In this way, when implanting the flexible neural electrode, by making the extension direction of the plurality of auxiliary implanting needles 20a perpendicular to the extension direction of the plurality of implanting portions 10a of the plurality of flexible neural electrodes 1a, the implanting depth of the flexible neural electrode can be controlled, so that the flexible neural electrode reaches the target tissue.

[0086] Figure 7 Only the case where the extension direction of the auxiliary implanting needle 20a is perpendicular to the extension direction of the implanting portion 10a of the flexible neural electrode 1a is shown, and it can be understood that in other embodiments of the present disclosure, the extension direction of the auxiliary implanting needle 20a can have a certain inclination angle with respect to the extension direction of the linear structure, for example, greater than 0 degrees and less than or equal to 90 degrees, which is also beneficial to control the implanting depth of the flexible neural electrode, and thus the present disclosure does not limit this.

[0087] In an embodiment of the present disclosure, the plurality of flexible neural electrodes 1 can include a plurality of implanting portions 10, a part of the plurality of implanting portions 10 is a linear structure as shown, and another part is a stretchable spiral structure as shown. Figure 7 Figure 1 In this way, different requirements for the implanted electrode can be met during the operation.

[0088] In an embodiment of the present disclosure, the shape of the implanting portion can be various, and only the linear structure and the spiral structure are shown above, and other structures such as spring structure, mesh structure, etc. can also be included. In addition, the shape of the spiral structure is not limited to the circular shape shown above, and other structures such as triangular shape, quadrilateral shape, polygonal shape, or rounded triangular shape, rounded quadrilateral shape, rounded polygonal shape, etc. can also be included.

[0089] Returning to Figure 4B , the flexible neural electrode composite structure 100 can further include a support assembly 4. The support assembly 4 connects the plurality of implanting portions of the plurality of flexible neural electrodes 1, plays a supporting role, and facilitates the overall transfer of the plurality of flexible neural electrodes 1. The support assembly 4 includes a first support component 41 and a second support component 42 connected with the first support component 41, wherein the first support component 41 includes the flexible insulating layer 101 and the conductive layer 102 of the flexible neural electrode 1. The second support component 42 only includes the flexible insulating layer 101 and plays an insulating role.

[0090] At least one embodiment of the present disclosure also provides a manufacturing method of a flexible neural electrode composite structure.

[0091] Figure 8 ​A flowchart of a manufacturing method of a flexible neural electrode composite structure is provided for embodiments of the present disclosure. As shown in Figure 8 FIG. 1, the manufacturing method of the flexible neural electrode composite structure 100 provided by embodiments of the present disclosure includes the following steps: Figure 1

[0092] S100: providing a plurality of flexible neural electrodes 1, each of which includes an implanting portion 10 and an auxiliary structure 11 formed on the implanting portion 10;

[0093] S200: forming an auxiliary implanting assembly 2, which includes a plurality of auxiliary implanting needles 20, each of which includes an auxiliary implanting end 201 located close to one end of the plurality of flexible neural electrodes 1;

[0094] S300: assembling the auxiliary implanting end 201 and the auxiliary structure 11; and

[0095] S400: fixing the assembled auxiliary implanting end 201 and the auxiliary structure 11.

[0096] In the manufacturing method of the flexible neural electrode composite structure provided by embodiments of the present disclosure, by fixing the auxiliary implanting assembly and the plurality of flexible neural electrodes together, the plurality of flexible neural electrodes can be implanted into the target tissue at the same time during the implanting process of the flexible neural electrodes. Compared with the single implanting method, on the one hand, the implanting time is shortened and the implanting difficulty is reduced, so as to realize the implanting of the flexible neural electrode array with high throughput and high coverage; on the other hand, before the implanting of the flexible neural electrode, the assembled flexible neural electrode and the auxiliary implanting assembly are fixed or connected together by the fixing object, so that the operation of assembling the flexible neural electrode and the auxiliary implanting assembly on site during the implanting is omitted, the implanting efficiency is improved, and the operation time is shortened; in addition, since the flexible neural electrode and the auxiliary implanting assembly are the assembled whole structure, the transportation and use are facilitated.

[0097] For example, in step S100, there are various methods for forming the flexible neural electrode 1, such as photolithography process, micro-electro-mechanical system (MEMS), etc.

[0098] In one example, the preparation method of the plurality of flexible neural electrodes includes the following steps:

[0099] S101: cleaning and drying the substrate.

[0100] For example, the substrate is a silicon wafer, which is cleaned by ultrasonic cleaning and dried by nitrogen blowing, and then cleaned by plasma.

[0101] S102: forming a plurality of grooves on the substrate, the plurality of grooves corresponding to a plurality of auxiliary structures 11 on a plurality of implanting portions 10 of the plurality of flexible neural electrodes 1.

[0102] ​For example, the auxiliary structure 11 can be a through hole, a groove or a protrusion. By providing a plurality of grooves, a space can be provided for the auxiliary implant end 201 to pass through the through hole when the auxiliary implant needle 20 is inserted into the through hole, facilitating the transfer of the electrode.

[0103] S103: Forming a sacrificial layer on the substrate with the plurality of grooves.

[0104] In the assembly of the flexible neural electrode array and the auxiliary implant assembly, by forming a sacrificial layer on the substrate, the flexible neural electrode array formed on the substrate is facilitated to be released. For example, the sacrificial layer can be one or more of polymethyl methacrylate (PMMA), aluminum (Al), nickel (Ni), etc. In the present embodiment, PMMA is used as the sacrificial layer, and the flexible neural electrode array is formed on the sacrificial layer. When the flexible neural electrode array is partially soaked in a solution such as acetone, the solution reaches the PMMA sacrificial layer, and when the PMMA sacrificial layer is completely dissolved, the flexible neural electrode array is released from the substrate.

[0105] S104: Forming a flexible neural electrode array on the substrate with the sacrificial layer.

[0106] For example, the flexible neural electrode array includes a plurality of flexible neural electrodes 1, each flexible neural electrode 1 including a flexible insulating layer 101 and a conductive layer 102, wherein the conductive layer 102 includes a plurality of conductive wires 103; the flexible neural electrode 1 further includes an implant portion 1 and an auxiliary structure 11 on the implant portion 1. By removing part of the flexible insulating layer 101 to expose part of the conductive wires 103 to form an electrode site 104. For example, the conductive layer 102 can be formed by a photolithography process.

[0107] In the present embodiment of the disclosure, the photolithography process includes but is not limited to coating photoresist, exposure with a mask plate, development, etching, stripping of remaining photoresist, etc. It can be understood that the conductive layer 102 can be only one layer, or can have multiple layers, each conductive layer 102 can be provided with a plurality of conductive wires 103, and adjacent conductive layers 102 are insulated from each other.

[0108] Figure 9 Structure diagram of the flexible neural electrode formed in the manufacturing method of the flexible neural electrode composite structure provided by the present disclosure. Figure 10 Structure diagram of the flexible neural electrode formed in the manufacturing method of the flexible neural electrode composite structure provided by the present disclosure. Figure 9 Structure diagram of the flexible neural electrode formed in the manufacturing method of the flexible neural electrode composite structure provided by the present disclosure. Structure diagram of the flexible neural electrode formed in the manufacturing method of the flexible neural electrode composite structure provided by the present disclosure.

[0109] Structure diagram of the flexible neural electrode formed in the manufacturing method of the flexible neural electrode composite structure provided by the present disclosure. Figure 9 Structure diagram of the flexible neural electrode formed in the manufacturing method of the flexible neural electrode composite structure provided by the present disclosure. Figure 10As shown, a circular recess 320 is formed in the silicon wafer 310 for accommodating the auxiliary implant needle passing through the auxiliary structure 11b, and the diameter of the circular recess 320 is 60 μm and the depth is 100 μm. A PMMA sacrificial layer 330 is formed on the silicon wafer 310 with the circular recess 320. The flexible neural electrode 1b is formed on the PMMA sacrificial layer 330. The flexible neural electrode 1b includes an implant portion 10b with a spiral structure. The implant portion 10b includes the auxiliary structure 11b (a through hole 111b as shown in the figure) and the electrode site 104b. The flexible neural electrode 1b further includes a conductive wire 103b connected with the electrode site 111b.

[0110] In the embodiments of the present disclosure, the diameter of the circular recess can be 5-100 μm, such as 5 μm, 10 μm, 20 μm, 25 μm, 30 μm, 40 μm, 50 μm, 100 μm, etc., for example, 40-60 μm; the depth of the circular recess can be 1-200 μm, such as 0 μm, 5 μm, 10 μm, 15 μm, 25 μm, 30 μm, 40 μm, 50 μm, 100 μm, 150 μm, 200 μm, etc., for example, 100-150 μm. The thickness of the sacrificial layer is 0-20 μm, such as 1 μm, 2 μm, 5 μm, 10 μm, 20 μm, etc., for example, 1 μm.

[0111] For example, the step S200 can further include:

[0112] S201: forming the auxiliary fixing member 21;

[0113] S202: forming the plurality of auxiliary implant needles 20;

[0114] S203: connecting the auxiliary fixing member 21 and the plurality of auxiliary implant needles 20 together.

[0115] Figures 11 to 13 A cross-sectional schematic view of the manufacturing method of the auxiliary implant assembly provided in the embodiments of the present disclosure is shown. For example, Figures 11 to 13 The manufacturing process of the auxiliary implant assembly of Figure 6 is shown, which includes the following steps:

[0116] 1) A plurality of commercial optical fibers 30 with a diameter of 250 μm are selected, each of which is composed of a high-purity silica (SiO2) core with a diameter of 125 μm and an acrylate coating with an outer diameter of 250 μm. The optical fiber 30 is cut into an optical fiber segment with a length of about 1 cm by an optical fiber cutter, and the acrylate coating at the tip of about 50 μm is stripped off by a wire stripper.

[0117] 2) As shown in Figure 11As shown, three silicon wafers 2111-2113 are selected as auxiliary fixation plates, and a plurality of holes 212 are formed on each silicon wafer. For example, the silicon wafer 2111 is etched by laser to obtain a plurality of holes 212 arranged in a 3x4 array. The 3x4 hole array is the same as the arrangement of the 3x4 through holes 111 of the flexible neural electrode array. The diameter of the hole 212 is, for example, 260 μm. Then, a plurality of optical fibers 30 are inserted into the corresponding 12 holes 212 of the silicon wafers 2111-2113 to serve as fixation and collimation. The silicon wafers 2111-2112 serve to collimate the plurality of optical fibers 30, and the silicon wafer 2113 is used for position fixation of the optical fibers 30.

[0118] 3) As shown in FIG. 3B, the tip of the optical fiber 30 is etched by a BOE (Buffered Oxide Etch) buffered oxide etchant. The etching process is as follows: first, the 125 μm core of the tip of the optical fiber 30 is etched to a diameter of about 60 μm; then, the optical fiber 30 is taken out of the etchant and washed with deionized water three times, and then immersed in 50°C anhydrous ethanol for soaking to remove the acrylate coating on the surface of the optical fiber 30; finally, the optical fiber 30 with the acrylate coating removed is further etched by the BOE buffered oxide etchant to obtain an optical fiber with a tip diameter of about 20 μm, and finally obtain the auxiliary implantation assembly as shown in FIG. 3C. Figure 12 Figure 13 As shown in FIG. 3B, the tip of the optical fiber 30 is etched by a BOE (Buffered Oxide Etch) buffered oxide etchant. The etching process is as follows: first, the 125 μm core of the tip of the optical fiber 30 is etched to a diameter of about 60 μm; then, the optical fiber 30 is taken out of the etchant and washed with deionized water three times, and then immersed in 50°C anhydrous ethanol for soaking to remove the acrylate coating on the surface of the optical fiber 30; finally, the optical fiber 30 with the acrylate coating removed is further etched by the BOE buffered oxide etchant to obtain an optical fiber with a tip diameter of about 20 μm, and finally obtain the auxiliary implantation assembly as shown in FIG. 3C.

[0119] 4) As shown in FIG. 3B, the tip of the optical fiber 30 is etched by a BOE (Buffered Oxide Etch) buffered oxide etchant. The etching process is as follows: first, the 125 μm core of the tip of the optical fiber 30 is etched to a diameter of about 60 μm; then, the optical fiber 30 is taken out of the etchant and washed with deionized water three times, and then immersed in 50°C anhydrous ethanol for soaking to remove the acrylate coating on the surface of the optical fiber 30; finally, the optical fiber 30 with the acrylate coating removed is further etched by the BOE buffered oxide etchant to obtain an optical fiber with a tip diameter of about 20 μm, and finally obtain the auxiliary implantation assembly as shown in FIG. 3C. Figure 13 Figure 6 As shown in FIG. 3B, the tip of the optical fiber 30 is etched by a BOE (Buffered Oxide Etch) buffered oxide etchant. The etching process is as follows: first, the 125 μm core of the tip of the optical fiber 30 is etched to a diameter of about 60 μm; then, the optical fiber 30 is taken out of the etchant and washed with deionized water three times, and then immersed in 50°C anhydrous ethanol for soaking to remove the acrylate coating on the surface of the optical fiber 30; finally, the optical fiber 30 with the acrylate coating removed is further etched by the BOE buffered oxide etchant to obtain an optical fiber with a tip diameter of about 20 μm, and finally obtain the auxiliary implantation assembly as shown in FIG. 3C.

[0120] In the above manufacturing method, a tungsten wire can also be used instead of the optical fiber 30 as an auxiliary implantation needle. In this case, the above step 4) can be replaced by the following step 4'):

[0121] The front end of the tungsten wire is immersed in a 2 mol / L NaOH solution for about 6 mm in length, and an electrochemical etching is performed in a constant potential mode of a CHI660 electrochemical workstation, with an overpotential of 5.0 V, to etch the diameter of the tungsten wire to about 100 μm; then, the tip of the tungsten wire is lifted up, and only the tip of the tungsten wire with a length of about 2 mm is immersed in the NaOH solution for further etching until the meniscus breaks, to obtain a tungsten wire with a flat tip, and finally obtain the auxiliary implantation assembly as shown in FIG. 3C. Figure 6

[0122] For example, before step S300, the above manufacturing method further includes: ​​​

[0123] S500: align the auxiliary implant end 201 to the auxiliary structure 11.

[0124] For example, aligning at least one of the plurality of auxiliary implant ends 201 to at least one of the plurality of auxiliary structures 11 facilitates faster assembly of the auxiliary implant end 201 and the auxiliary structure 11.

[0125] For example, the auxiliary implant assembly 2 is pre-fixed by a stereotactic instrument, and the array of flexible neural electrodes 1 is adjusted to be aligned to the auxiliary implant assembly 2 on a rotating table, for example, a multi-axis precision air bearing rotating table that can rotate at multiple angles.

[0126] For example, the step S400 can further comprise forming a fixing 3 at least at the connection between the auxiliary implant end 201 and the auxiliary structure 11, as shown in Figure 2 and Figure 3 For example, the fixing 3 at least fills 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. Further, for example, the fixing 3 is formed as a film that connects the plurality of auxiliary implant ends 201 and the plurality of auxiliary structures 11 together. The specific material of the fixing 3 can refer to the description of the previous embodiments, which will not be repeated here.

[0127] In one example, after the auxiliary implant assembly and the array of flexible neural electrodes are formed, the following steps are performed:

[0128] a) Place the silicon wafer 310 formed with the circular grooves 320, the PMMA sacrificial layer 330, and the plurality of flexible neural electrodes 1b (hereinafter referred to as the array of flexible neural electrodes) on a multi-axis precision air bearing rotating table;

[0129] b) Fix the top of the auxiliary implant assembly 2 prepared in Figure 6 on a stereotactic instrument that can move in three dimensions;

[0130] c) Adjust the stereotactic instrument to gradually lower the auxiliary implant assembly 2 to approach the surface of the array of flexible neural electrodes, and adjust the X, Y, Z axes of the air bearing rotating table to align the tips of the plurality of optical fibers 30 of the auxiliary implant assembly 2 with the plurality of through holes 111b in the array of flexible neural electrodes;

[0131] d) Continue to lower the auxiliary implant assembly 2 until the tips of the plurality of optical fibers 30 are inserted into the plurality of circular grooves 320 of the silicon wafer 310;

[0132] e) Drop 5% PVA aqueous solution on the tips of the optical fibers 30 and the surface of the array of flexible neural electrodes, and after the water in it evaporates, the array of flexible neural electrodes and the auxiliary implant assembly 2 are fixed by PVA;

[0133] f) Immerse the flexible neural electrode array in acetone for release. The amount of acetone should be above the PMMA sacrificial layer. Once the PMMA sacrificial layer is completely dissolved, the flexible neural electrode array is released, resulting in a flexible neural electrode array composite electrode.

[0134] At least one embodiment of this disclosure also provides a composite structure assembly, which includes a plurality of flexible neural electrode composite structures described in any of the foregoing embodiments.

[0135] Figure 14 This is a schematic diagram of the composite structure component provided in an embodiment of the present disclosure.

[0136] like Figure 14 As shown, the composite structure assembly 40 includes multiple flexible neural electrode composite structures 410 (e.g., three shown in the figure), each flexible neural electrode composite structure 410 having a similar structure to the preceding one. Figure 1 The flexible neural electrode composite structure 100 shown has the same construction.

[0137] For example, the composite structure assembly 40 also includes a connection portion 420 having multiple conductive lines. Each conductive line is connected between the electrode site of the flexible neural electrode and a pad (not shown) to enable signal transmission.

[0138] In the composite structure assembly provided in this embodiment, since each flexible neural electrode composite structure uses a fixation device to fix the auxiliary implantation end and the auxiliary structure, thereby fixing the auxiliary implantation assembly and multiple flexible neural electrodes together, multiple flexible neural electrodes can be implanted simultaneously during the flexible neural electrode implantation process 431.

[0139] To the target tissue. Compared to the method of implanting individual electrodes one by one, on the one hand, it shortens the implantation time and reduces the implantation difficulty, thereby achieving the implantation of high-throughput, high-coverage flexible neural electrode arrays; on the other hand, before implanting the flexible neural electrodes, fixators are used to fix or connect the assembled flexible neural electrodes and auxiliary implantation components together, eliminating the need to assemble the flexible neural electrodes and auxiliary implantation components on-site during implantation, improving implantation efficiency and shortening surgical time; in addition, since the flexible neural electrodes and auxiliary implantation components are assembled as a whole structure, they are easy to transport and use.

[0140] At least one embodiment of this disclosure also provides a method for implanting a flexible neural electrode employing the flexible neural electrode composite structure described in any of the preceding embodiments.

[0141] Figure 15 The adoption provided for the embodiments of this disclosure Figure 1 An implantation method for a flexible neural electrode with a flexible neural electrode composite structure.

[0142] Combination Figure 1 and Figure 15 The above-mentioned implantation methods include:

[0143] S1: The mobile flexible neural electrode composite structure 100 drives the implantation portion 10 of multiple flexible neural electrodes 1 to move to the surface of the target tissue.

[0144] S2: Melt or dissolve the fixative 3 to make the auxiliary implantation end 201 and the auxiliary structure 11 separable;

[0145] S3: Move the assistive implantation component 2 toward the target tissue to move the multiple implantation portions 10 of the multiple flexible neural electrodes 1 to the target tissue; and

[0146] S4: Remove the auxiliary implantation component 2 and leave at least a portion of the flexible neural electrodes 1 at the target tissue.

[0147] For example, when moving the auxiliary implantation component 2 towards the target tissue, multiple implantation portions 10 of the multiple flexible neural electrodes 1 simultaneously move to the target tissue. When removing the auxiliary implantation component 2, it can be lifted to detach it from the flexible neural electrodes 1 remaining on the target tissue, thus allowing the auxiliary implantation component 2 to be reused or discarded. The flexible neural electrodes remaining on the target tissue can be some or all of the multiple flexible neural electrodes 1. When all the flexible neural electrodes 1 remain on the target tissue, more electrode sites can be provided on the target tissue.

[0148] like Figure 1 As shown, when each implanted portion 10 is a stretchable spiral structure, the auxiliary structure 11 is located on the stretchable spiral structure. Thus, when the auxiliary implantation component 2 is moved toward the target tissue to move the multiple implanted portions 10 of the multiple flexible neural electrodes 1 to the target tissue, the auxiliary implantation end 201 can be used to push the auxiliary structure 11 downward so that the stretchable spiral structure unfolds in the z-direction.

[0149] like Figure 7 As shown, each implanted portion 10a is a linear structure, and the auxiliary structure 11a is located on the linear structure. Thus, when the auxiliary implantation component 2a is moved towards the target tissue to move the multiple implanted portions 10a of the multiple flexible neural electrodes 1a to the target tissue, the auxiliary implantation end 201a can be used to move the auxiliary structure 11a, thereby moving the linear structure to the target tissue. Figure 1 Compared to the spiral structure shown, Figure 7 During implantation, the rear end of the flexible neural electrode 1a needs to be pushed along with the front end, or the rear end of the flexible neural electrode 1a needs to be folded before implantation to reserve a certain length, thereby reserving implantation space for the overall implantation of the flexible neural electrode.

[0150] The implantation method of the flexible neural electrode provided by the embodiments of the present disclosure can implant multiple flexible neural electrodes into target tissue at the same time. Compared with the single implantation method, on the one hand, the implantation time is shortened, and the implantation difficulty is reduced, so that high-throughput and high-coverage flexible neural electrode array implantation is realized; on the other hand, before implanting the flexible neural electrode, the assembled flexible neural electrode and the auxiliary implantation assembly are fixed or connected together by using the fixing object, so that the operation of assembling the flexible neural electrode and the auxiliary implantation assembly on site during implantation is omitted, the implantation efficiency is improved, and the operation time is shortened; in addition, since the flexible neural electrode and the auxiliary implantation assembly are an assembled whole structure, transportation and use are facilitated.

[0151] In one example, the implantation method of the flexible neural electrode comprises the following steps:

[0152] (1) Rat anesthesia: healthy SPF rats are taken, and the rats are anesthetized by injecting pentobarbital sodium at a standard of 0.01 g / mL; after the rats are deeply anesthetized, the rats are fixed on a stereotaxic instrument, and subsequent gas anesthesia is performed with a small animal anesthetic; the rat's head is disinfected with an iodophor-dipped cotton swab, and the hair is cut off; the rat's scalp is cut along the midline with scissors, the surface tissue of the skull is cleaned, and the clean skull is exposed.

[0153] (2) Craniotomy window: a 5mm×7mm rectangular craniotomy window is drilled 2.5mm before and after the rat's anterior fontanel and 3.5mm left and right of the midline with a skull drill, and the dura mater is carefully removed to provide a position for implanting the flexible neural electrode.

[0154] (3) Electrode implantation: the flexible neural electrode composite structure fixed by the PVA film prepared in any of the preceding embodiments is fixed on the stereotaxic instrument, and is gradually moved close to the rat's brain surface craniotomy window; after the PVA film of the flexible neural electrode array contacts the brain surface, physiological saline is added to the gap between the PVA film and the silicon wafer to dissolve the PVA film; after the PVA film is dissolved, the flexible neural electrode is completely released, and the electrode implantation is started, and the stereotaxic instrument clamping rod is lowered at a speed of about 20 μm / s. After the height is counted after the optical fiber tip contacts the brain surface, the clamping rod is continued to be lowered to an implantation depth of 1.5mm, and the implantation is stopped; the auxiliary implantation assembly is lifted up at a speed of about 100 μm / s, and the electrode implantation is completed; finally, the skull hole is sealed with isolation glue, and dental cement is applied between the electrode and the iron sheet support to fix them.

[0155] The implantation method of the flexible neural electrode provided by the embodiments of the present disclosure can implant multiple flexible neural electrodes into target tissue at the same time. Compared with the single implantation method, on the one hand, the implantation time is shortened, and the implantation difficulty is reduced, so that high-throughput and high-coverage flexible neural electrode array implantation is realized; on the other hand, before implanting the flexible neural electrode, the assembled flexible neural electrode and the auxiliary implantation assembly are fixed or connected together by using the fixing object, so that the operation of assembling the flexible neural electrode and the auxiliary implantation assembly on site during implantation is omitted, the implantation efficiency is improved, and the operation time is shortened; in addition, since the flexible neural electrode and the auxiliary implantation assembly are an assembled whole structure, transportation and use are facilitated.

[0156] Reference Figure 14 The implantation method includes sequentially implanting the first group of flexible neural electrodes 431, the second group of flexible neural electrodes 432, and the third group of flexible neural electrodes 433 into the target tissue by using the plurality of flexible neural electrode composite structures 410, each group of flexible neural electrodes including, for example, 12 flexible neural electrodes. Alternatively, the first group of flexible neural electrodes 431, the second group of flexible neural electrodes 432, and the third group of flexible neural electrodes 433 can also be implanted into the target tissue at the same time by using the plurality of flexible neural electrode composite structures 410. By the above method, the implantation efficiency can be improved, and the implantation time can be shortened.

[0157] The at least one embodiment of the present disclosure also provides an auxiliary implantation assembly. For example, as shown in Figure 5 The auxiliary implantation assembly 2 includes an auxiliary fixing member 21 including at least one auxiliary fixing plate 211, and a plurality of auxiliary implantation needles 20 configured to be connected with the at least one auxiliary fixing plate 211, and the extension direction (z direction shown in the figure) of the plurality of auxiliary implantation needles 20 is not parallel to the plane (xy plane shown in the figure) in which the at least one auxiliary fixing plate 211 is located.

[0158] For example, the at least one auxiliary fixing plate 211 and the plurality of auxiliary implantation needles 20 are detachably connected or fixedly connected. For example, the at least one auxiliary fixing plate 211 is provided with an opening 212, and the plurality of auxiliary implantation needles 20 include a fixing end 202 opposite to the auxiliary implantation end 201, and the fixing end 202 is configured to pass through the opening 212 to be connected with the at least one auxiliary fixing plate 211.

[0159] For example, as shown in Figure 6 The auxiliary implantation assembly 2 further includes an adhesive 22, and at least part of the adhesive 22 is located between the at least one auxiliary fixing plate and the plurality of auxiliary implantation needles 20.

[0160] By using the auxiliary implantation assembly provided by the embodiments of the present disclosure, the implantable flexible neural electrode array can be transferred and implanted as a whole. Compared with single implantation, the array implantation and transfer method can greatly improve the transfer, release, and implantation efficiency, reduce the implantation time, and provide a simple and efficient method for large-scale implantation of the implantable flexible neural electrode array. In the implantation method provided by the embodiments of the present disclosure, the implantation speed is 1-200 μm / s (micrometers / second), such as 1 μm / s, 5 μm / s, 10 μm / s, 15 μm / s, 20 μm / s, 30 μm / s, 50 μm / s, 100 μm / s, 200 μm / s, for example, 10 μm / s-20 μm / s.

[0161] In this document, the following points need to be noted:

[0162] (1) The drawings of the embodiments of the present disclosure only relate to the structures involved in the embodiments of the present disclosure, and other structures can be referred to the general design.

[0163] (2) In the case of no conflict, the embodiments of the present disclosure and the features in the embodiments can be combined with each other to obtain new embodiments.

[0164] The above only describes exemplary embodiments of the present disclosure, and is not intended to limit the protection scope of the present disclosure, and the protection scope of the present disclosure is determined by the appended claims.

Claims

1. A flexible neural electrode composite structure, comprising: a flexible neural electrode array comprising a plurality of flexible neural electrodes arranged in an array, each of the flexible neural electrodes comprising an implant portion and an auxiliary structure disposed on the implant portion; an auxiliary implant assembly comprising a plurality of auxiliary implant needles corresponding to the plurality of flexible neural electrodes, the plurality of auxiliary implant needles arranged in an array, each of the auxiliary implant needles comprising an auxiliary implant end located proximate to one end of the corresponding flexible neural electrode, the auxiliary implant end configured to assemble with the auxiliary structure; and a fixation configured to fix the assembled auxiliary implant end and the auxiliary structure; wherein the fixation is located at least at the junction of the auxiliary implant end and the auxiliary structure, and at least a portion of the fixation is located between the auxiliary implant end and the auxiliary structure to maintain the relative position between the auxiliary implant end and the auxiliary structure, wherein the extension direction of the plurality of auxiliary implant needles is not parallel to the extension direction of the plurality of implant portions of the plurality of flexible neural electrodes, wherein the implant portion is a stretchable coil structure, the auxiliary structure is located on the stretchable coil structure, and the auxiliary implant end of the auxiliary implant needle is configured to push down the auxiliary structure to cause the stretchable coil structure to expand in the extension direction of the auxiliary implant needle.

2. The flexible neural electrode composite structure of claim 1, wherein the extension direction of the plurality of auxiliary implant needles is not parallel to the plane on which the plurality of coil structures are located.

3. The flexible neural electrode composite structure of claim 2, wherein the auxiliary structure is located at the end of the stretchable coil structure.

4. The flexible neural electrode composite structure of claim 1, wherein the extension direction of the plurality of auxiliary implant needles is perpendicular to the extension direction of the plurality of implant portions of the plurality of flexible neural electrodes.

5. The flexible neural electrode composite structure of claim 1, wherein the auxiliary implant end and the auxiliary structure are configured to be assembled together by a plug-in manner.

6. The flexible neural electrode composite structure of claim 5, wherein the auxiliary implant end is configured to be partially or fully inserted into the auxiliary structure.

7. The flexible neural electrode composite structure of claim 6, wherein the auxiliary structure is a through hole, a groove, or a protrusion on the implant portion.

8. The flexible neural electrode composite structure of claim 5, wherein the cross-sectional shape of each of the auxiliary implant needles comprises one of a triangle, a rectangle, a circle, an ellipse, and a regular polygon.

9. The flexible neural electrode composite structure of claim 5, wherein the material of each of the auxiliary implant needles comprises one or more of a metal and a non-metal.

10. The flexible neural electrode composite structure of claim 1, wherein the auxiliary implant assembly further comprises: an auxiliary fixation located on the side of the plurality of auxiliary implant needles distal to the plurality of flexible neural electrodes and configured to fix the plurality of auxiliary implant needles. ​ 11. The flexible neural electrode composite structure of claim 10, wherein the auxiliary fixation member comprises an auxiliary fixation plate, and a plane of the auxiliary fixation plate is not parallel to an extension direction of the plurality of auxiliary implant needles.

12. The flexible neural electrode composite structure of claim 11, wherein the plane of the auxiliary fixation plate is perpendicular to the extension direction of the plurality of auxiliary implant needles.

13. The flexible neural electrode composite structure of claim 11, wherein the auxiliary fixation plate is configured to be detachably connected or fixedly connected with the plurality of auxiliary implant needles.

14. The flexible neural electrode composite structure of claim 13, wherein the auxiliary fixation plate is provided with a plurality of openings, and the plurality of auxiliary implant needles comprise fixed ends away from the auxiliary implant ends along the extension direction, and the fixed ends are configured to pass through the plurality of openings to be connected with the auxiliary fixation plate.

15. The flexible neural electrode composite structure of claim 11, wherein the auxiliary implant assembly further comprises: an adhesive, at least part of which is located between the auxiliary fixation plate and the plurality of auxiliary implant needles and configured to bond the auxiliary fixation plate and the plurality of auxiliary implant needles with each other.

16. The flexible neural electrode composite structure of claim 1, wherein the fixation comprises one or more of a photo-fusible material, a thermal-fusible material, a liquid- swellable material, and a liquid-soluble material.

17. The flexible neural electrode composite structure of claim 16, wherein the liquid- soluble material comprises one or more of a polyvinyl alcohol, a silk fibroin, a polyethylene glycol, and a gelatin; and the liquid comprises one or more of ultrapure water, a physiological saline, and a phosphate buffer.

18. The flexible neural electrode composite structure of claim 1, wherein the fixation is in the form of a membrane, and the membrane fixes the plurality of auxiliary implant ends and the plurality of auxiliary structures together.

19. The flexible neural electrode composite structure of claim 18, wherein the membrane fixes at least a plurality of junctions between the plurality of auxiliary implant ends and the plurality of auxiliary structures together.

20. A method of manufacturing a flexible neural electrode composite structure, comprising: providing a flexible neural electrode array, the flexible neural electrode array comprising a plurality of flexible neural electrodes arranged in an array, each of the flexible neural electrodes comprising an implant portion and an auxiliary structure formed on the implant portion; forming an auxiliary implant assembly, the auxiliary implant assembly comprising a plurality of auxiliary implant needles arranged in an array, each of the auxiliary implant needles comprising an auxiliary implant end located on a side close to the plurality of flexible neural electrodes; assembling the auxiliary implant ends with the auxiliary structures; and fixing the assembled auxiliary implant ends and the auxiliary structures. ​ wherein the fixed assembly of the auxiliary implant end and the auxiliary structure comprises forming a fixture at least at a junction of the auxiliary implant end and the auxiliary structure, such that at least a portion of the fixture is located between the auxiliary implant end and the auxiliary structure to maintain a relative position between the auxiliary implant end and the auxiliary structure, wherein the extension direction of the plurality of auxiliary implant needles is not parallel to the extension direction of the plurality of implant portions of the plurality of flexible neural electrodes, wherein the implant portion is a stretchable coiled structure, the auxiliary structure is located on the stretchable coiled structure, and the auxiliary implant end of the auxiliary implant needle is configured to push down the auxiliary structure so as to expand the stretchable coiled structure in the extension direction of the auxiliary implant needle.

21. The manufacturing method of claim 20, wherein, Before assembling the auxiliary implant end with the auxiliary structure, the manufacturing method further comprises aligning the auxiliary implant end with the auxiliary structure.

22. The manufacturing method of claim 21, wherein, Aligning the auxiliary implant end with the auxiliary structure comprises aligning at least one auxiliary implant end of the plurality of auxiliary implant ends with at least one auxiliary structure of the plurality of auxiliary structures.

23. A composite assembly comprising a plurality of the flexible neural electrode composite structures of any one of claims 1 to 19.

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