A tree-shaped flexible electrode and a preparation method and an implantation method thereof

Abstract

The present application relates to a kind of tree-shaped flexible electrode and its preparation method and implantation method, the tree-shaped flexible electrode includes stem structure and branch structure;The branch structure includes at least two levels of branch structure;One end of first branch structure is connected with the side surface of stem structure;One end of lower level branch structure is connected with the side surface of upper level branch structure;The last level branch structure is tip structure;Conductive circuit is arranged on the stem structure and the branch structure;At least one electrode site is arranged on the tip structure.The stem structure is mainly used to arrange conductive circuit and external input-output interface, and the branch structure is used to extend to target area, and the tip structure is mainly used for electrical signal recording and regulation in target area.The tree-shaped flexible neural electrode structure provided by the present application is conducive to reducing the implantation trauma of high-throughput electrode, and can be used for three-dimensional and high-time-space resolution neural electrical signal acquisition and stimulation.

Description

Technical Field

[0001] This invention relates to the fields of neural engineering and bioelectronics, and in particular to a tree-shaped flexible electrode and its preparation and implantation methods. Background Technology

[0002] With the development of neuroscience and brain-computer interfaces in recent years, implantable flexible neural electrodes are increasingly used in neural signal recording and electrical stimulation. Compared with traditional implantable rigid neural electrodes, implantable flexible neural electrodes have a more compatible mechanical fit with brain tissue, which can greatly reduce the micro-movement of the electrode after implantation, reduce the immune response of the electrode to brain tissue, and achieve long-term stable recording and stimulation of neural signals.

[0003] Existing implantable flexible neural electrodes are often arranged linearly on both sides of the implantation structure. To maintain stability during implantation, the overall structure is often quite wide to prevent electrode breakage. However, a large overall structure size further increases the risk of implantation injury and can trigger a stronger acute immune response. Furthermore, the recording sites linearly distributed on both sides of the overall structure cannot directly interact with the neural tissue, making it difficult to perform high spatiotemporal resolution neural recording and stimulation.

[0004] Existing technologies have drawbacks such as large overall structural size of flexible neural electrodes, significant damage during implantation, and inability to directly interact with neural tissue. Therefore, how to further reduce implantation damage and enhance the direct interaction between flexible electrodes and neural tissue to achieve high spatiotemporal resolution neural recording has become an urgent problem to be solved. Summary of the Invention

[0005] To address the aforementioned technical problems, the present invention aims to provide a tree-shaped flexible electrode and its preparation and implantation methods. The tree-shaped flexible neural electrode structure provided by the present invention helps to reduce the implantation trauma of high-throughput electrodes and can be used for three-dimensional and high spatiotemporal resolution neural electrical signal acquisition and stimulation. After implantation, it can form multi-dimensional interactions with neurons, covering more complex three-dimensional neural networks.

[0006] To achieve this objective, the present invention adopts the following technical solution:

[0007] In a first aspect, the present invention provides a tree-shaped flexible electrode, the tree-shaped flexible electrode comprising a trunk structure and a branch structure; the branch structure comprising at least two levels of branch structure;

[0008] One end of the first branch structure is connected to the side of the main structure; one end of the next-level branch structure is connected to the side of the previous-level branch structure; the last-level branch structure is a terminal structure; conductive lines are arranged on the main structure and the branch structures; at least one electrode site is arranged on the terminal structure.

[0009] The tree-shaped flexible electrode provided by this invention includes a trunk structure and a branch structure. The trunk structure is mainly used to lay out conductive lines and external input / output interfaces. The branch structure is mainly used to lay out conductive lines to extend to the target area. The terminal structure is mainly used to lay out electrode sites for recording and controlling electrical signals in the target area.

[0010] The tree-shaped flexible neural electrode structure provided by this invention helps reduce the implantation trauma of high-throughput electrodes and can be used for three-dimensional and high spatiotemporal resolution neural electrical signal acquisition and stimulation. After implantation, it can form multi-dimensional interactions with neurons, covering more complex three-dimensional neural networks.

[0011] In this invention, "high throughput" refers to the fact that the multi-level structure of the electrode can accommodate more electrode sites, thus greatly increasing the number of channels in the electrode.

[0012] The following are preferred technical solutions of the present invention, but are not intended to limit the technical solutions provided by the present invention. The technical objectives and beneficial effects of the present invention can be better achieved and realized through the following preferred technical solutions.

[0013] Preferably, the width of different hierarchical structures in the tree-shaped flexible electrode decreases progressively.

[0014] The tree-shaped flexible electrode provided by this invention has different electrode structure widths between different layers, and the widths decrease layer by layer to reduce the mechanical compatibility between different layers, match the nerve dendrites, facilitate the deformation of the overall structure, and reduce implantation damage and resistance.

[0015] Preferably, the branching structure includes a two-level hierarchical structure, namely a first branching structure and a terminal structure.

[0016] To further reduce implantation damage, this invention uses a tree-shaped flexible electrode with a two-level hierarchical structure as an example to demonstrate the specific structure and parameters. To further expand the signal capture area, the number of hierarchical structures can be further increased.

[0017] Preferably, the width of the main structure is 100μm-300μm, for example, it can be 100μm, 120μm, 140μm, 150μm, 160μm, 180μm, 200μm, 220μm, 240μm, 250μm, 260μm, 280μm or 300μm, but is not limited to the listed values, and other unlisted values ​​within the range are also applicable.

[0018] Preferably, the length of the main structure is 10mm-50mm, for example, it can be 10mm, 15mm, 20mm, 25mm, 30mm, 35mm, 40mm, 45mm or 50mm, but is not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0019] Preferably, the width of the first branch structure is 50μm-100μm, for example, it can be 50μm, 52μm, 54μm, 55μm, 56μm, 58μm, 60μm, 65μm, 70μm, 75μm, 80μm, 85μm, 90μm, 95μm or 100μm, but is not limited to the listed values, and other unlisted values ​​within the range are also applicable.

[0020] Preferably, the length of the first branch structure is 3mm-10mm, for example, it can be 3mm, 3.5mm, 4mm, 4.5mm, 5mm, 5.5mm, 6mm, 6.5mm, 7mm, 7.5mm, 8mm, 8.5mm, 9mm, 9.5mm, or 10mm, but is not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0021] Preferably, the width of the terminal structure is 3μm-50μm, for example, it can be 3μm, 5μm, 10μm, 15μm, 20μm, 25μm, 30μm, 35μm, 40μm, 45μm or 50μm, but is not limited to the listed values, and other unlisted values ​​within the range are also applicable.

[0022] In this invention, the width of the terminal structure is further controlled to be 3μm-50μm. A narrower terminal structure can not only reduce the implantation trauma of high-throughput electrodes, but also be used for three-dimensional and high spatiotemporal resolution neural electrical signal acquisition and stimulation. If the width of the terminal structure is too large, it cannot form a compatible neural interface with the neural tissue; if the width of the terminal structure is too narrow, it is easy to break during the implantation process.

[0023] Preferably, the length of the distal structure is 1mm-5mm, for example, it can be 1mm, 1.5mm, 2mm, 2.5mm, 3mm, 3.5mm, 4mm, 4.5mm or 5mm, but is not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0024] Preferably, the ratio of the number of main structures to the number of first branch structures is 1:(2-100), for example, it can be 1:2, 1:5, 1:8, 1:10, 1:20, 1:30, 1:40, 1:50, 1:60, 1:70, 1:80, 1:90 or 1:100, but is not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0025] Preferably, the ratio of the number of the first branch structures to the number of the terminal structures is 1:(2-10), for example, it can be 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9 or 1:10, but is not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0026] In this invention, the number of first branch structures on the main trunk structure can be adjusted as needed. When the length of the main trunk structure is long enough, the number of first branch structures can be increased. Similarly, the number of terminal structures on the first branch structure can be adjusted as needed. When the length of the first branch structure is long enough, the number of terminal structures can be increased.

[0027] The present invention further controls the ratio of the number of trunk structures to the number of first branch structures to be 1:(2-100), and the ratio of the number of first branch structures to the number of terminal structures to be 1:(2-10). Within an appropriate ratio range, while reducing the density of first branch structures and terminal structures to reduce implantation damage, the signal detection area can be expanded as much as possible.

[0028] Preferably, an auxiliary implantation structure is provided at the end of the main structure that forms an obtuse angle with the first branch structure.

[0029] Preferably, the auxiliary implantation structure is a hole or groove, which facilitates the assembly of the flexible electrode and the rigid auxiliary implant.

[0030] Preferably, the angle between the first branch structure and the side of the main structure opposite to where the auxiliary implantation structure is located is 30°-60°, for example, it can be 30°, 32°, 34°, 35°, 36°, 38°, 40°, 42°, 44°, 45°, 46°, 48°, 50°, 52°, 54°, 55°, 56°, 58° or 60°, but is not limited to the listed values, and other unlisted values ​​within the range are also applicable.

[0031] The angle between the first branch structure of the tree-shaped flexible electrode provided by this invention and the side opposite to the auxiliary implantation structure in the trunk structure is 30°-60°. The size of the angle mainly affects the deformation of the electrode during the implantation process. An acute angle is more conducive to the electrode attaching to the trunk structure and reducing implantation damage; while an obtuse angle may be easily torn during the implantation process because the force is downward.

[0032] Preferably, the angle between the terminal structure and the side of the branch structure furthest from the main structure is 15°-45°, for example, it can be 15°, 20°, 22°, 24°, 25°, 26°, 28°, 30°, 32°, 34°, 35°, 36°, 38°, 40°, 42°, 44° or 45°, but is not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0033] The tree-shaped flexible electrode provided by this invention has an angle of 15°-45° between its terminal structure and the side of the branch structure furthest from the trunk in the previous level, which facilitates interaction with nerve dendrites. Because the angle of the terminal structure is narrower, it is more easily deformed and may bundle together during implantation, implanting into the target area along with the branch structure of the electrode. At the same time, the different bifurcation angles between different levels match the nerve dendrites, facilitating the deformation of the overall structure and reducing implantation damage and resistance. If the angle between the terminal structure and the side of the branch structure furthest from the trunk in the previous level is too large, the electrode will not deform easily during implantation, which may cause greater implantation damage. If the angle between the terminal structure and the side of the branch structure furthest from the trunk in the previous level is too small, the terminal structures will directly adhere to each other, resulting in an insufficient detection area.

[0034] Preferably, the electrode sites arranged in the terminal structure include conductive polymers or conductive polymers with conductive metal nanoparticles electroplated or coated on their surface.

[0035] In this invention, in order to reduce the impedance of the electrode sites, the electrode site surface modification method includes electroplating conductive metal nanoparticles and conductive polymers or coating conductive polymers on the site surface.

[0036] Preferably, the diameter of the electrode site is 10μm-30μm, for example, it can be 10μm, 20μm, 21μm, 22μm, 23μm, 24μm, 25μm, 26μm, 27μm, 28μm, 29μm or 30μm, but is not limited to the listed values, and other unlisted values ​​within the range are also applicable.

[0037] Preferably, the spacing between the electrode sites is 20μm-50μm, for example, it can be 20μm, 22μm, 24μm, 25μm, 26μm, 28μm, 30μm, 32μm, 34μm, 35μm, 36μm, 38μm, 40μm, 42μm, 44μm, 45μm, 46μm, 48μm or 50μm, but is not limited to the listed values, and other unlisted values ​​within the range are also applicable.

[0038] In a second aspect, the present invention provides a method for preparing a dendritic flexible electrode as described in the first aspect, the method comprising the following steps:

[0039] (1) A photoresist layer is coated on the substrate and etched to form a patterned marking pattern;

[0040] (2) Prepare a sacrificial layer on the graphic marking pattern prepared in step (1);

[0041] (3) Coat the sacrificial layer prepared in step (2) with a flexible insulating substrate layer;

[0042] (4) A photoresist layer is coated on the flexible insulating substrate layer prepared in step (3), and patterned conductive lines and electrode sites are formed by etching. Then an adhesion layer and a conductive layer are prepared, and the electrode sites, conductive lines and electrical input and output ports are obtained by peeling.

[0043] (5) A flexible insulating layer is prepared on the electrode sites, conductive lines and electrical input / output port layers prepared in step (4);

[0044] (6) Photoresist is coated on the flexible insulating layer prepared in step (5), and a photoresist mask is formed by etching. Then, the electrode sites and welding points are exposed by dry etching.

[0045] (7) Remove the sacrificial layer prepared in step (2) to obtain a dendritic flexible electrode.

[0046] The method for fabricating the tree-shaped flexible electrode provided by the present invention is a micro-nano fabrication process, including patterning of the conductive layer by photolithography and metal deposition, and patterning of inorganic carbon materials to form at least one conductive layer.

[0047] Preferably, the substrate used in step (1) is cleaned and dried with acetone and water, and then cleaned with oxygen plasma.

[0048] Preferably, the photoresist in step (1) includes S1813 positive photoresist.

[0049] Preferably, the material of the sacrificial layer in step (2) includes aluminum and / or nickel.

[0050] Preferably, the etching step (4) includes pre-baking, exposure and development processes in sequence.

[0051] Preferably, the flexible insulating substrate and flexible insulating layer in steps (3) and (5) are made of any one or a combination of at least two of polyimide, SU-8 or parylene.

[0052] Preferably, the conductive layer in step (4) comprises any one or a combination of at least two of gold, platinum, liquid metal or graphene.

[0053] In this invention, the flexible electrode uses a metal and inorganic carbon material with good ductility as the conductive layer to reduce the influence of the conductive layer on the overall deformation.

[0054] Preferably, the material of the adhesive layer in step (4) includes Cr.

[0055] Preferably, the conductive layer in step (4) is made of Au.

[0056] Preferably, the method for preparing the adhesion layer and the conductive layer in step (4) includes electron beam evaporation.

[0057] Preferably, the thickness of the adhesion layer and the conductive layer in step (4) is 5nm-30nm, for example, it can be 5nm, 6nm, 7nm, 8nm, 9nm, 10nm, 15nm, 20nm, 25nm, 30nm, 35nm, 40nm, 45nm or 50nm, but is not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0058] Preferably, the thickness of the conductive layer in step (4) is 50nm-5000nm, for example, it can be 50nm, 100nm, 200nm, 300nm, 400nm, 500nm, 600nm, 700nm, 800nm, 900nm, 1000nm, 1500nm, 2000nm, 2500nm, 3000nm, 3500nm, 4000nm, 4500nm or 5000nm, but is not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0059] Preferably, the flexible insulating substrate and flexible insulating layer in steps (3) and (5) each include at least two layers, such as two, three, four or five layers, but not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0060] Preferably, the method for removing the sacrificial layer in step (7) is to soak the dendritic flexible electrode in ferric chloride solution to release it.

[0061] Thirdly, the present invention provides a method for implanting a tree-shaped flexible electrode as described in the first aspect, the method comprising the following steps:

[0062] Step 1: Connect one end of the rigid auxiliary implantation needle to the tree-shaped flexible electrode through the auxiliary implantation structure;

[0063] Step 2: Implant the rigid auxiliary implantation needle and the tree-shaped flexible electrode into the target area;

[0064] Step 3: Remove the rigid auxiliary implantation needle from the target area, leaving the tree-shaped flexible electrode in the target area to complete the implantation.

[0065] The implantation method of the tree-shaped flexible electrode involves assembling a steel needle with an auxiliary implantation hole or groove and implanting it with the flexible electrode. After reaching the target point, the steel needle is removed, leaving the flexible electrode in the target area.

[0066] The layered structure in the tree-shaped flexible electrode provided by this invention can shrink and deform during implantation, reducing damage during implantation and enabling high-throughput integration of flexible electrodes.

[0067] Fourthly, the present invention provides an application of the flexible electrode as described in the first aspect, wherein the tree-shaped flexible electrode is used for high-throughput and high spatiotemporal resolution neural signal acquisition and stimulation.

[0068] The flexible electrode provided by this invention can be used for high-throughput and high spatiotemporal resolution neural signal acquisition and stimulation, enabling the simultaneous acquisition of a large number of neuronal signals through a greater number of channels and in greater data volume. High spatiotemporal resolution refers to high temporal and spatial resolution, the ability to accurately capture changes in neural signals over a short period of time, and the ability to precisely distinguish neural signals at different locations in the brain.

[0069] The numerical range described in this invention includes not only the point values ​​listed above, but also any point values ​​within the numerical ranges not listed above. Due to space limitations and for the sake of brevity, this invention will not exhaustively list all the specific point values ​​included in the range.

[0070] Compared with the prior art, the present invention has at least the following beneficial effects:

[0071] (1) By setting up a multi-level branch structure, the flexible electrode wiring and recording sites are distributed on different hierarchical structures. The main structure can ensure the implantation stability of the flexible electrode, and the terminal structure can ensure the effective interaction between the recording site and the nerve tissue and improve the recording resolution.

[0072] (2) The tree-shaped hierarchical structure provided by the present invention can shrink and deform during the implantation process, reducing damage during the implantation process, and can be used for high-throughput integration of flexible electrodes. Attached Figure Description

[0073] Figure 1 This is a schematic diagram of the tree-shaped flexible electrode structure of Embodiment 1 of the present invention, wherein 1-tree-shaped flexible electrode, 2-main trunk structure, 3-first branch structure, 4-terminal structure, 5-electrode site, and 6-auxiliary implantation hole;

[0074] Figure 2 This is a schematic diagram of the layered structure of the tree-shaped flexible electrode in Embodiment 1 of the present invention, wherein 7-flexible base layer, 8-electrode structure, and 9-flexible insulating layer;

[0075] Figure 3 This is a flowchart of the processing of the tree-shaped flexible electrode according to Embodiment 1 of the present invention;

[0076] Figure 4 This is a schematic diagram of the tree-shaped flexible electrode implantation method according to Embodiment 1 of the present invention, wherein 10 is a rigid auxiliary implantation needle. Detailed Implementation

[0077] The technical solution of the present invention will be further described below with reference to the accompanying drawings and specific embodiments. However, the following examples are merely simplified examples of the present invention and do not represent or limit the scope of protection of the present invention. The scope of protection of the present invention is determined by the claims.

[0078] Unless otherwise specified, all reagents and consumables used in the following examples and comparative examples were purchased from conventional reagent manufacturers in the art; unless otherwise specified, the experimental methods and techniques used were conventional methods and techniques in the art.

[0079] Example 1

[0080] This embodiment provides a tree-shaped flexible electrode, the structural schematic of which is shown below. Figure 1 As shown, the tree-shaped flexible electrode includes a trunk structure 2, a first branch structure 3, and a terminal structure 4; one end of the first branch structure is connected to the side of the trunk structure; one end of the terminal structure is connected to the side of the first branch structure; an auxiliary implantation structure, namely an auxiliary implantation hole 6, is provided at the end of the trunk structure that forms an obtuse angle with the first branch structure.

[0081] The main structure has a width of 200μm and a length of 20mm;

[0082] The angle between the first branch structure and the side opposite to the auxiliary implantation structure in the main structure is 45°; the width of the first branch structure is 80μm, the length is 4mm, and the number is 4;

[0083] The bifurcation angle between the terminal structure and the first-order branch structure is 35°; the width of the terminal structure is 25μm and the length is 1mm, and there are 3 terminal structures on each first-order branch structure.

[0084] The method for fabricating a tree-shaped flexible electrode provided in this embodiment includes the following steps, and the process flow diagram of the tree-shaped flexible electrode is as follows: Figure 3 As shown:

[0085] (1) The substrate is cleaned with acetone and water, then dried, and then cleaned with oxygen plasma. S1813 positive photoresist is spin-coated onto the substrate, and a patterned marking pattern is formed by pre-baking, exposure and development.

[0086] (2) An aluminum sacrificial layer is deposited on the pattern obtained after step (1) by electron beam evaporation, and the aluminum sacrificial layer and the marking pattern are peeled off;

[0087] (3) Spin-coating polyimide onto one side of the aluminum sacrificial layer formed in step (2), and baking it to form a flexible insulating substrate layer;

[0088] (4) S1813 positive photoresist is spin-coated onto the flexible insulating substrate layer formed in step (3). After pre-baking, exposure and development, patterned electrode sites and connecting lines are formed. Then, a 5nm Cr adhesion layer and a 100nm Au conductive layer are formed by electron beam evaporation. Then, electrode sites, connecting lines and electrical input and output ports are prepared by peeling.

[0089] (5) Polyimide is spin-coated onto the metal layer of the electrode sites, connecting lines and electrical input / output ports formed in step (4), and a flexible insulating layer is formed after baking;

[0090] (6) Photoresist is spin-coated onto the flexible insulating layer formed in step (5), and after pre-baking, exposure, post-baking and development, a photoresist mask is formed. The electrode sites and welding points are exposed by dry etching to prepare a flexible electrode structure.

[0091] (7) The flexible electrode obtained in step (6) is diced to obtain a single flexible electrode chip, and then the sacrificial layer is removed by ferric chloride solution to obtain a tree-shaped flexible electrode 1.

[0092] A schematic diagram of the layered structure of the fabricated tree-shaped flexible electrode is shown below. Figure 2 As shown, 7 is a flexible substrate, 8 is an electrode structure, and 9 is a flexible insulating layer.

[0093] Example 2

[0094] This embodiment provides a tree-shaped flexible electrode, which includes a trunk structure, a first branch structure, and a terminal structure; one end of the first branch structure is connected to the side of the trunk structure; one end of the terminal structure is connected to the side of the first branch structure; an auxiliary implantation structure, namely an auxiliary implantation hole, is provided at the end of the trunk structure that forms an obtuse angle with the first branch structure.

[0095] The main structure has a width of 100μm and a length of 10mm;

[0096] The angle between the first branch structure and the side opposite to the auxiliary implantation structure in the main structure is 55°; the width of the first branch structure is 50μm, the length is 3mm, and the number is 6.

[0097] The bifurcation angle between the terminal structure and the first branch structure is 40°; the width of the terminal structure is 30μm and the length is 1mm, and there are 7 terminal structures on each first branch structure.

[0098] The method for preparing the tree-shaped flexible electrode provided in this embodiment is the same as that in Embodiment 1.

[0099] Example 3

[0100] This embodiment provides a tree-shaped flexible electrode, which includes a trunk structure, a first branch structure, a second branch structure, and a terminal structure; one end of the first branch structure is connected to the side of the trunk structure; one end of the second branch structure is connected to the side of the first branch structure; one end of the terminal structure is connected to the side of the second branch structure; an auxiliary implantation structure, namely an auxiliary implantation hole, is provided at the end of the trunk structure that forms an obtuse angle with the first branch structure.

[0101] The main structure has a width of 300 μm and a length of 50 mm;

[0102] The angle between the first branch structure and the side opposite to the auxiliary implantation structure in the main structure is 45°; the width of the first branch structure is 100μm, the length is 10mm, and the number is 80.

[0103] The bifurcation angle between the second branch structure and the first branch structure is 35°; the width of the second branch structure is 100μm and the length is 10mm; there are 15 second branch structures on each first branch structure.

[0104] The bifurcation angle between the terminal structure and the second branch structure is 20°; the width of the terminal structure is 50μm and the length is 4mm, and there are 8 terminal structures on each second branch structure.

[0105] The method for preparing the tree-shaped flexible electrode provided in this embodiment is the same as that in Embodiment 1.

[0106] Example 4

[0107] This embodiment provides a tree-shaped flexible electrode, which differs from Embodiment 1 only in that the width of the terminal structure is 1 μm, while the other steps are the same as in Embodiment 1.

[0108] Example 5

[0109] This embodiment provides a tree-shaped flexible electrode, which differs from Embodiment 1 only in that the width of the terminal structure is 80 μm, while the other steps are the same as in Embodiment 1.

[0110] Example 6

[0111] This embodiment provides a tree-shaped flexible electrode, which differs from Embodiment 1 only in that the angle between the first branch structure and the side opposite to the auxiliary implantation structure in the main structure is 20°, and the rest of the steps are the same as in Embodiment 1.

[0112] Example 7

[0113] This embodiment provides a tree-shaped flexible electrode, which differs from Embodiment 1 only in that the angle between the first branch structure and the side opposite to the main trunk structure where the auxiliary implantation structure is located is 70°. All other steps are the same as in Embodiment 1.

[0114] Example 8

[0115] This embodiment provides a tree-shaped flexible electrode, which differs from Embodiment 1 only in that the bifurcation angle between the terminal structure and the first branch structure is 10°, while the rest of the steps are the same as in Embodiment 1.

[0116] Example 9

[0117] This embodiment provides a tree-shaped flexible electrode, which differs from Embodiment 1 only in that the bifurcation angle between the terminal structure and the first branch structure is 60°, while the rest of the steps are the same as in Embodiment 1.

[0118] Comparative Example 1

[0119] This comparative example provides a flexible electrode, which differs from Example 1 only in that the flexible electrode includes a main structure and a first branch structure, but does not contain a terminal structure, and the preparation method is the same as that of Example 1.

[0120] Application Example 1

[0121] This application example provides a method for implanting a tree-shaped flexible electrode, as illustrated in the schematic diagram below. Figure 4 As shown, it includes the following steps:

[0122] Step 1: Connect one end of the rigid auxiliary implantation needle 10 to the tree-shaped flexible electrode 1 prepared in Example 1 through the auxiliary implantation hole 6;

[0123] Step 2: Implant the rigid auxiliary implantation needle and the tree-shaped flexible electrode into the mouse brain;

[0124] Step 3: Remove the rigid auxiliary implantation needle from the mouse brain, leaving the tree-shaped flexible electrode in the mouse brain to complete the implantation.

[0125] Application Examples 2-9

[0126] Application Examples 2-9 each provide a method for implanting a tree-shaped flexible electrode. The only difference between the tree-shaped flexible electrode implantation method and Application Example 1 is that the tree-shaped flexible electrode prepared in Examples 2-9 is used.

[0127] Comparative Application Example 1

[0128] This comparative application example 1 provides a method for implanting a flexible electrode. The only difference between this method and application example 1 is that the flexible electrode prepared in comparative example 1 is used.

[0129] Test method: The dendritic flexible electrodes prepared in the examples and comparative examples were tested.

[0130] The test results show that:

[0131] (1) As can be seen from Examples 1-3, the present invention, by setting a multi-level branching structure, distributes the flexible electrode wiring and recording sites on different hierarchical structures. The trunk structure can ensure the implantation stability of the flexible electrode, while the terminal structure can ensure effective interaction between the recording sites and neural tissue and improve the recording resolution. The tree-like hierarchical structure can shrink and deform during implantation, reducing damage during the implantation process, and can be used for high-throughput integration of flexible electrodes.

[0132] (2) By comparing Example 1 with Examples 4-5, it can be seen that the present invention further controls the width of the terminal structure to 3μm-50μm. The narrower terminal structure can not only reduce the implantation trauma of high-throughput electrodes, but also be used for three-dimensional and high spatiotemporal resolution neural electrical signal acquisition and stimulation. If the width of the terminal structure is too large, it cannot form a compatible neural interface with the neural tissue; if the width of the terminal structure is too narrow, it is easy to break during the implantation process.

[0133] (3) By comparing Example 1 with Examples 6-7, it can be seen that the present invention further controls the angle between the peripheral structure and the side of the upper-level branch structure away from the main structure to be 15°-45°, which facilitates interaction with the nerve dendrites. If the angle between the peripheral structure and the side of the upper-level branch structure away from the main structure is too large, the electrode is not easy to deform during implantation, which can easily cause greater implantation damage. If the angle between the peripheral structure and the side of the upper-level branch structure away from the main structure is too small, the peripheral structures will directly adhere to each other, resulting in a small detection area.

[0134] (4) By comparing Example 1 with Examples 8-9, it can be seen that the present invention further controls the angle between the first branch structure of the tree-shaped flexible electrode and the side opposite to the auxiliary implantation structure in the trunk structure to be 30°-60°, which facilitates the deformation of the overall structure of the flexible electrode and reduces implantation damage.

[0135] (5) As can be seen from Example 1 and Comparative Example 1, the present invention arranges the terminal structure and sets up electrode sites on the terminal structure. The electrical signals are collected by the electrode sites on the terminal structure for recording and regulating the electrical signals of the target area. While reducing implantation damage, it can expand the contact area between the electrode sites and the nerve tissue and increase the detection area.

[0136] In summary, this invention, through a multi-level branching structure, distributes the flexible electrode wiring and recording sites across different hierarchical levels. The trunk structure ensures the implantation stability of the flexible electrode, while the terminal structure ensures effective interaction between the recording sites and neural tissue, and improves recording resolution. The tree-like hierarchical structure can contract and deform during implantation, reducing damage and enabling high-throughput integration of flexible electrodes.

[0137] The applicant declares that the above description is only a specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Those skilled in the art should understand that any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention fall within the protection and disclosure scope of the present invention.

Claims

1. A tree-shaped flexible electrode, characterized in that, The tree-shaped flexible electrode includes a trunk structure and a branch structure; the branch structure includes at least two levels of branch structure. One end of the first branch structure is connected to the side of the main structure; one end of the next level branch structure is connected to the side of the previous level branch structure; the last level branch structure is the terminal structure. Conductive lines are arranged on the main structure and the branch structure. At least one electrode site is provided on the terminal structure.

2. The tree-shaped flexible electrode according to claim 1, characterized in that, The width of different hierarchical structures in the tree-shaped flexible electrode decreases progressively. Preferably, the first branch structure is arranged alternately on both sides of the main structure.

3. The tree-shaped flexible electrode according to claim 1 or 2, characterized in that, The branching structure includes a two-level hierarchical structure, namely a first branching structure and a terminal structure; Preferably, the width of the main structure is 100μm-300μm and the length is 10mm-50mm; Preferably, the width of the first branch structure is 50μm-100μm and the length is 3mm-10mm; Preferably, the width of the terminal structure is 3μm-50μm and the length is 1mm-5mm; Preferably, the ratio of the number of the main structure to the number of the first branch structure is 1:(2-100); Preferably, the ratio of the number of the first branch structures to the number of the terminal structures is 1:(2-10).

4. The tree-shaped flexible electrode according to any one of claims 1-3, characterized in that, An auxiliary implantation structure is provided at the end of the main structure that forms an obtuse angle with the first branch structure; Preferably, the auxiliary implantation structure is a hole or a groove.

5. The tree-shaped flexible electrode according to any one of claims 1-4, characterized in that, The angle between the first branch structure and the side opposite to the auxiliary implantation structure in the main structure is 30°-60°. Preferably, the angle between the terminal structure and the side of the branch structure furthest from the main trunk is 15°-45°. Preferably, the electrode sites arranged in the terminal structure include conductive polymers or conductive polymers with conductive metal nanoparticles electroplated or coated on the surface. Preferably, the diameter of the electrode sites is 10μm-30μm, and the spacing between the electrode sites is 20μm-50μm.

6. A method for preparing a tree-shaped flexible electrode as described in any one of claims 1-5, characterized in that, The preparation method includes the following steps: (1) A photoresist layer is coated on the substrate and etched to form a patterned marking pattern; (2) Prepare a sacrificial layer on the graphic marking pattern prepared in step (1); (3) Coat the sacrificial layer prepared in step (2) with a flexible insulating substrate layer; (4) A photoresist layer is coated on the flexible insulating substrate layer prepared in step (3), and patterned conductive lines and electrode sites are formed by etching. Then an adhesion layer and a conductive layer are prepared, and the electrode sites, conductive lines and electrical input and output ports are obtained by peeling. (5) A flexible insulating layer is prepared on the electrode sites, conductive lines and electrical input / output port layers prepared in step (4); (6) Photoresist is coated on the flexible insulating layer prepared in step (5), and a photoresist mask is formed by etching. Then, the electrode sites and welding points are exposed by dry etching. (7) Remove the sacrificial layer prepared in step (2) to obtain a dendritic flexible electrode.

7. The preparation method according to claim 6, characterized in that, The photoresist in step (1) includes S1813 positive photoresist; Preferably, the material of the sacrificial layer in step (2) includes aluminum and / or nickel; Preferably, the flexible insulating substrate and flexible insulating layer in steps (3) and (5) are made of any one or a combination of at least two of polyimide, SU-8 or parylene.

8. The preparation method according to claim 6 or 7, characterized in that, The conductive layer in step (4) comprises any one or a combination of at least two of gold, platinum, liquid metal or graphene; Preferably, the thickness of the adhesion layer in step (4) is 5 nm-30 nm; Preferably, the thickness of the conductive layer in step (4) is 50nm-5000nm; Preferably, the flexible insulating substrate and the flexible insulating layer in steps (3) and (5) each comprise at least two layers; Preferably, the method for removing the sacrificial layer in step (7) is to soak the dendritic flexible electrode in ferric chloride solution to release it.

9. A method for implanting a tree-shaped flexible electrode as described in any one of claims 1-5, characterized in that, The implantation method includes the following steps: Step 1: Connect one end of the rigid auxiliary implantation needle to the tree-shaped flexible electrode through the auxiliary implantation structure; Step 2: Implant the rigid auxiliary implantation needle and the tree-shaped flexible electrode into the target area; Step 3: Remove the rigid auxiliary implantation needle from the target area, leaving the tree-shaped flexible electrode in the target area to complete the implantation.

10. Use of a tree-shaped flexible electrode as described in any one of claims 1-5, characterized in that, The tree-shaped flexible electrode is used for high-throughput and high spatiotemporal resolution neural signal acquisition and stimulation.

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