A neural interface with a degradable coating

Abstract

The application belongs to the technical field of neural interface, and particularly relates to a neural interface with a degradable coating, which comprises at least one flexible electrode, at least one auxiliary structure and a degradable coating, wherein the flexible electrode is bonded to the auxiliary structure through the degradable coating. The flexible electrode is bonded to the auxiliary structure through a degradable material, so that the flexible electrode can be easily implanted into brain tissue under the assistance of the auxiliary structure, after a period of time, the cerebrospinal fluid in the brain tissue dissolves the degradable material, the flexible electrode is separated from the auxiliary structure, the auxiliary structure is pulled out, and the flexible electrode remains in the brain tissue. The method for implanting the flexible electrode through microneedle paving assistance has small implantation injury, can increase the stability of long-term implantation, and the flexible electrode comprises multiple body electrodes, can adapt to the structural deformation of brain tissue, avoids the generation of foreign body sensation caused by friction with tissue organs, can realize multi-electrode recording, and improves spatial resolution and signal accuracy.

Description

Technical Field

[0001] This application relates to the field of neural interface technology, and more specifically to a neural interface with a biodegradable coating. Background Technology

[0002] A neural interface is a communication system that bypasses the normal output pathways composed of peripheral nerves and muscles, providing a new pathway for exchanging information with external devices. It can stimulate nerve cells to generate action potentials through external devices, or record the action potentials generated by nerve cells, thereby achieving bidirectional communication between nerve cells and external devices. Therefore, neural interfaces are widely used in the research and treatment of various neurological diseases.

[0003] Neural interface devices are mainly divided into implantable and non-implantable types. Compared to non-implantable neural electrodes, implantable neural electrodes have received significant attention from scholars both domestically and internationally due to their high resolution. Currently, most implantable microneedle structures utilize EcoG, Utah electrodes, Michigan electrodes, and sewing machine flexible electrodes. Among implantable neural electrodes, microneedle array electrodes, represented by Utah electrodes, possess high spatial resolution and exhibit the highest stability during long-term implantation. They are the only neural interface devices approved by the U.S. Food and Drug Administration (FDA) for use in humans. However, in practical applications, implantable microneedles require craniotomy for implantation, which is challenging and can cause significant implantation damage, affecting organ and tissue activity and growth, thus hindering long-term implantation. Therefore, a better solution is needed to address the problems in existing technologies. Summary of the Invention

[0004] The main purpose of this application is to propose a neural interface that aims to solve the technical problem that current implantable neural interface microneedle arrays cause significant damage to brain tissue and cannot achieve long-term implantation.

[0005] To solve the above-mentioned technical problems, according to one aspect of this application, the following technical solution is provided: a neural interface is provided, comprising: at least one flexible electrode, at least one auxiliary structure and a biodegradable coating, wherein the flexible electrode is bonded to the auxiliary structure by the biodegradable coating.

[0006] Furthermore, the biodegradable coating comprises silk fibroin.

[0007] Furthermore, according to the set concentration of silk protein solution, spin coating speed, and number of spin coatings, silk protein solution is coated on the flexible electrode to form the biodegradable coating.

[0008] Furthermore, the biodegradable coating is doped with PLGA, PVA, PEG, gelatin, chitosan, maltose, or sucrose to adjust the softening and dissolving time.

[0009] Furthermore, the doping ratio is 10% to 50%.

[0010] Furthermore, the biodegradable coating comprises polyethylene glycol.

[0011] Furthermore, the polyethylene glycol is analytical grade polyethylene glycol with a viscosity-average molecular weight of 10,000 g / mol or higher.

[0012] Furthermore, at least one electrode point is provided on the front side of the flexible electrode, and the biodegradable coating is on the back side of the flexible electrode.

[0013] Furthermore, the flexible electrode and the auxiliary structure are arranged in a one-to-one correspondence, and the flexible electrode and the auxiliary structure have the same shape.

[0014] Furthermore, the flexible electrode is provided with at least one slit. When the flexible electrode is provided with at least two slits, the slits are spaced apart along the length direction of the flexible electrode, and adjacent two slits are staggered. The slits are perpendicular or inclined to the length direction of the flexible electrode.

[0015] Compared with the prior art, this application has the following beneficial effects:

[0016] This application provides a neural interface with a rigid auxiliary structure. A flexible electrode is adhered to the auxiliary structure using a biodegradable material, allowing the flexible electrode to be easily implanted into neural tissue with the assistance of the auxiliary structure. After a period of time, the biodegradable material dissolves, separating the flexible electrode from the auxiliary structure. The auxiliary structure can then be removed, leaving only the flexible electrode in the brain tissue. The flexible electrode can adaptively deform according to the expansion and contraction of blood vessels, reducing implantation damage. Attached Figure Description

[0017] To more clearly illustrate the technical solutions of this application, the accompanying drawings used in the embodiments will be briefly described below. It should be understood that the following drawings only show some embodiments of this application and should not be considered as a limitation on the scope of protection of this application. In the various drawings, similar components are numbered similarly.

[0018] Figure 1 This is a schematic diagram of the exploded structure of the microneedle-assisted implantable neural interface proposed in the embodiments of this application;

[0019] Figure 2 This is a schematic diagram of a single structure of the microneedle-assisted implantable neural interface proposed in the embodiments of this application;

[0020] Figure 3 This is a schematic diagram of the microneedle-assisted implantable neural interface array structure proposed in the embodiments of this application;

[0021] Figure 4 This is a schematic diagram of the bonding between the auxiliary structure and the flexible electrode proposed in the embodiments of this application.

[0022] Among them, 1-integrated circuit chip, 2-flexible electrode, 3-body electrode point, 4-auxiliary structure, 5-adhesive end. Detailed Implementation

[0023] The technical solutions in the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this application, and not all embodiments.

[0024] The components of the embodiments of this application described and illustrated in the accompanying drawings can be arranged and designed in a variety of different configurations. Therefore, the following detailed description of the embodiments of this application provided in the drawings is not intended to limit the scope of the claimed application, but merely to illustrate selected embodiments of the application. All other embodiments obtained by those skilled in the art based on the embodiments of this application without inventive effort are within the scope of protection of this application.

[0025] In the following, the terms “comprising,” “having,” and their cognates, which may be used in various embodiments of this application, are intended only to indicate a particular feature, number, step, operation, element, component, or combination thereof, and should not be construed as excluding, firstly, the presence of one or more other features, numbers, steps, operations, elements, components, or combinations thereof, or adding the possibility of one or more features, numbers, steps, operations, elements, components, or combinations thereof.

[0026] Furthermore, the terms "first," "second," and "third" are used only to distinguish descriptions and should not be interpreted as indicating or implying relative importance.

[0027] Unless otherwise specified, all terms used herein (including technical and scientific terms) shall have the same meaning as commonly understood by one of ordinary skill in the art to which the various embodiments of this application pertain. Terms (such as those defined in commonly used dictionaries) shall be interpreted as having the same meaning as in their contextual meaning in the relevant technical field and shall not be construed as having an idealized or overly formal meaning, unless clearly defined in the various embodiments of this application.

[0028] Example 1

[0029] This embodiment provides a neural interface, including: at least one flexible electrode, at least one auxiliary structure, and a biodegradable coating. The flexible electrode is adhered to the auxiliary structure via the biodegradable coating. The flexible electrode and the auxiliary structure are arranged in a one-to-one correspondence, and the flexible electrode and the auxiliary structure have the same shape. In other embodiments, the number of auxiliary structures may be less than the number of flexible electrodes, as long as the auxiliary structures facilitate the implantation of the flexible electrode into the target location.

[0030] In this embodiment, at least one electrode point is provided on the front side of the flexible electrode, and the biodegradable coating is provided on the back side of the flexible electrode to prevent the biodegradable coating from covering the electrode point. Specifically, the bulk electrode point is provided on the front side of the flexible electrode, and the auxiliary structure is provided on the back side of the flexible electrode.

[0031] Furthermore, the neural interface also includes an integrated circuit chip connected to the body electrode point, which is used to acquire neural signals, and the integrated circuit chip is used to receive and analyze the neural signals acquired by the body electrode point.

[0032] In an optional embodiment, the flexible electrode may use a flexible material as a substrate to ensure that the flexible electrode can deform under external force. The flexible material includes PDMS to ensure that the electrode contacts nerve tissue in a more flexible manner.

[0033] In another optional embodiment, the flexible electrode is provided with at least one slit. When the flexible electrode is provided with at least two slits, the slits are spaced apart along the length direction of the flexible electrode, and adjacent slits are staggered. The slits are perpendicular or inclined to the length direction of the flexible electrode so that the flexible electrode can deform.

[0034] Specifically, the flexible electrode can use a rigid material as a substrate. The body electrode specifically includes a substrate and a plurality of slits distributed on the substrate. The slits are spaced apart along the length direction of the body electrode (hereinafter referred to as the first direction for ease of description), with adjacent slits staggered, and the slits are perpendicular or inclined to the first direction. The slits can be perpendicular to the length direction of the body electrode (i.e., the first direction) or inclined to the length direction of the body electrode. Setting slits on the substrate can reduce the rigidity of the entire body electrode to a certain extent, but the size of the slits needs to be controlled within a certain range and cannot be too small, otherwise it will cause a lack of flexibility.

[0035] Here, the shape of the slit is not specifically limited; it can be elongated, wavy, serrated, etc.

[0036] In one embodiment, the biodegradable coating comprises silk fibroin. Specifically, the biodegradable coating can be formed by coating the flexible electrode with a silk fibroin solution according to a set concentration, spin-coating speed, and spin-coating times, thereby forming the biodegradable coating.

[0037] Furthermore, the biodegradable coating is doped with PLGA, PVA, PEG, gelatin, chitosan, maltose, or sucrose to adjust the softening and dissolving time. Specifically, other materials with different dissolving times, such as PLGA, PVA, PEG, gelatin, and maltose / sucrose, are mixed into the silk protein solution to further regulate the softening and dissolving time of the biodegradable coating, thereby meeting the implantation time requirements for target areas at different depths. The doping ratio is 10%–50%.

[0038] In another alternative embodiment, the biodegradable coating comprises polyethylene glycol, wherein the polyethylene glycol is analytical grade polyethylene glycol with a viscosity-average molecular weight of 10,000 g / mol or higher.

[0039] In this embodiment, the auxiliary structure is rigid. A flexible electrode is adhered to the auxiliary structure using a biodegradable material, allowing the flexible electrode to be easily implanted into the neural tissue with the assistance of the auxiliary structure. After a period of time, the biodegradable material dissolves, separating the flexible electrode from the auxiliary structure. The auxiliary structure is then removed, leaving only the flexible electrode in the brain tissue. The flexible electrode can adaptively deform according to the expansion and contraction of blood vessels, reducing implantation damage.

[0040] Example 2

[0041] like Figure 1 As shown, this application provides a neural interface including an integrated circuit chip 1 and at least one flexible electrode 2. When there are multiple flexible electrodes 2, they are spaced apart. The flexible electrodes 2 are made of a flexible material. This application does not have any particular limitation on the material of the flexible material, as long as it is not harmful to human tissue. According to one embodiment of this application, the material of the flexible electrode 2 is preferably polyimide. The polyimide substrate is fabricated into a multi-contact flexible electrode 2 using micromachining. The flexible electrode 2 is electrically connected to the integrated circuit chip 1. The flexible electrode 2 includes at least one body electrode point 3, which can realize signal output and weak electrical stimulation signal input.

[0042] The neural interface also includes at least one auxiliary structure 4, which is configured one-to-one with the flexible electrode 2. The flexible electrode has the same shape as the auxiliary structure. The surface of the auxiliary structure 4 is smooth, and its width is greater than the width of the flexible electrode 2. The flexible electrode 2 can be attached to the surface of the auxiliary structure 4. In use, a portion of the flexible electrode 2 to be implanted into the brain tissue, preferably the end of the flexible electrode 2, is bonded to the auxiliary structure 4 with a biodegradable material to form an attachment assembly. This assembly is then inserted into the brain tissue. After a period of time, the auxiliary structure 4 separates from the flexible electrode 2. The auxiliary structure 4 is then removed, leaving the flexible electrode 2 in the brain tissue while the auxiliary structure 4 is removed from the body, thus preventing long-term implantation damage.

[0043] like Figure 1-3 As shown, in an optional embodiment of this application, there are multiple auxiliary structures 4 and multiple flexible electrodes 2, which form an electrode array after being bonded to the integrated circuit chip 1. The spacing between the auxiliary structures 4 is the same as the spacing between the flexible electrodes 2, and the auxiliary structures 4 and flexible electrodes 2 can correspond one-to-one to achieve good adhesion. Figure 2 As shown; multiple microneedle electrode components can be combined to form a microneedle electrode array, such as Figure 3 As shown. When implanted into brain tissue, it can form regional coverage, improving spatial resolution and signal accuracy.

[0044] In an optional embodiment of this application, the material used to bond the flexible electrode 2 to the auxiliary structure 4 is a biodegradable material. This application does not have any particular restrictions on the material of the biodegradable material, as long as it is harmless to human tissue and can be degraded in brain tissue. Chitosan or silk protein is preferred. When the flexible electrode 2 bonded by the biodegradable material is implanted into human brain tissue with the assistance of the auxiliary structure 5, the biodegradable material at the bonding site can dissolve under the action of cerebrospinal fluid, realizing the separation of the auxiliary structure 4 from the flexible electrode 2. The auxiliary structure 5 can be easily removed, reducing damage to brain tissue.

[0045] In another optional embodiment of this application, the flexible electrode 2 can be cut to obtain flexible electrodes 2 of different lengths, and a protective film is provided at the cut end of the cut flexible electrode 2.

[0046] like Figure 1 As shown, the flexible electrode 2 includes at least one body electrode point 3. These body electrode points 3 are independent of each other and can operate independently under the control of the integrated circuit chip 1. Having multiple body electrode points 3 on a single flexible electrode 2 ensures that signal reading and stimulation occur simultaneously. In one optional embodiment, the body electrode points 3 on the flexible electrode 2 can be distributed in the same column or in different columns, depending on the width of the flexible electrode 2 and the actual situation.

[0047] like Figure 4 As shown, in an optional embodiment of this application, to better achieve the detachment and separation of the auxiliary structure 4 and the flexible electrode 2, the auxiliary structure 4 is designed as a stepped structure, that is, the thickness of the end of the auxiliary structure is greater than the thickness of the upper end, and the transition area of ​​the step is an inclined structure. The end of the flexible electrode 2, which is matched and bonded to it, is also an inclined wedge structure, which can fit into the upper region of the auxiliary structure 4 to form a component with the same thickness as the end of the auxiliary structure 4. This avoids the frictional resistance generated by the flexible electrode 2 being externally bonded to the auxiliary structure 4, eliminates the risk of the flexible electrode 2 falling off during assisted implantation, and reduces the area where biodegradable materials are used to bond the flexible electrode 2 and the auxiliary structure 4. That is, a smaller adhesive end 5 is needed to assistedly implant the flexible electrode 2 into the brain tissue, reducing the amount of biodegradable material used and also reducing the impact of biodegradable material dissolution on the brain tissue.

[0048] In one alternative embodiment, the neural interface further includes an external device comprising a data acquisition unit and a processing unit. The data acquisition unit is used to acquire external sensory signals; the processing unit is used to convert the sensory signals into stimulus signals for reproducing the sensory information.

[0049] In one alternative embodiment, the external device further includes a first wireless coil and a second wireless coil disposed on the side of the integrated circuit chip; the first wireless coil is used to transmit stimulation signals and the second wireless coil is used to receive stimulation signals.

[0050] Example 2

[0051] According to one embodiment of this application, a method for implanting a neural interface using microneedles based on biodegradable materials is also provided, the specific technical solution of which is as follows:

[0052] First, the size of the array of flexible electrodes 2 to be implanted, as well as the length of each flexible electrode 2 and the number of body electrode points 3, are determined according to the experimental or treatment plan. Then, a corresponding microneedle array is selected. The auxiliary structures 4 in the microneedle array can have the same length, and the flexible electrode 2 can be adhered to any position on the auxiliary structure. Alternatively, the lengths of the auxiliary structures 4 in the microneedle array can be different, matching the length of the auxiliary structure 4 to the length of the flexible electrode 2. Then, the flexible electrode 2 is adhered to the auxiliary structure 4. This application does not impose any particular limitation on the adhesion location between the flexible electrode 2 and the auxiliary structure 4. In an optional embodiment, at least a portion of the end of the flexible electrode 2 is adhered to the auxiliary structure 4, forming an adhesive end 5, so that the auxiliary structure 4 and the flexible electrode 2 are attached. The adhesive force formed by the adhesive end 5 at least ensures that the flexible electrode 2 can be inserted into the brain tissue without falling off during insertion. After the combined structure of auxiliary structure 4 and flexible electrode 2 is inserted into the brain tissue, it is left to stand for a period of time. In an optional embodiment, the standing time is greater than 15 minutes. After the biodegradable material dissolves, the auxiliary structure 4 is pulled out to achieve desorption treatment. The flexible electrode with multiple body electrode points 3 is left in the open brain tissue to realize signal output and weak electrical stimulation signal input.

[0053] The microneedle-assisted implantation method of flexible electrodes used in this application results in less implantation damage, which can increase the stability of long-term implantation. Furthermore, the flexible electrode includes multiple body electrodes, which can adapt to the structural deformation of brain tissue, avoid the discomfort caused by friction with tissues and organs, and enable multi-electrode recording, thereby improving spatial resolution and signal accuracy.

[0054] This application employs a stepped auxiliary structure and a wedge-shaped flexible electrode design, which avoids the frictional resistance caused by the flexible electrode being externally attached to the auxiliary structure, eliminates the risk of the flexible electrode falling off during assisted implantation, and reduces the scope of using biodegradable materials to bond the flexible electrode and the auxiliary structure, thereby reducing the amount of biodegradable materials used and also reducing the impact of biodegradable material dissolution on brain tissue.

[0055] The embodiments described above are merely illustrative of several implementation methods of this application, and while the descriptions are specific and detailed, they should not be construed as limiting the scope of this patent application. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of this application, and these all fall within the protection scope of this application. Therefore, the protection scope of this patent application should be determined by the appended claims.

Claims

1. A neural interface, characterized by, The application relates to a flexible electrode, which comprises at least one flexible electrode, at least one auxiliary structure and a degradable coating, wherein the flexible electrode is bonded to the auxiliary structure through the degradable coating, the degradable coating comprises silk fibroin, and PLGA, PVA, PEG, gelatin, chitosan, maltose or sucrose is doped in the degradable coating to adjust a softening and dissolving time, and the doping ratio is 10%-50%; the auxiliary structure is a step structure, the thickness of the end of the auxiliary structure is greater than the thickness of the upper end, the transition area of the step is an inclined structure, the end of the flexible electrode matched with the auxiliary structure is an inclined wedge structure, and the flexible electrode is embedded in the upper area of the auxiliary structure to form an assembly with the same thickness as the end of the auxiliary structure. According to a set silk fibroin solution concentration, spin coating speed and spin coating times, a silk fibroin solution is coated on the flexible electrode to form the degradable coating.

2. The neural interface of claim 1, wherein, The degradable coating comprises polyethylene glycol.

3. The neural interface of claim 1, wherein, The polyethylene glycol is analytical pure polyethylene glycol with a viscosity average molecular weight of 10000 g / mol or above.

4. The neural interface of claim 3, wherein, The front surface of the flexible electrode is provided with at least one electrode point, and the degradable coating is arranged on the back surface of the flexible electrode.

5. The neural interface of any one of claims 1-4, wherein, The flexible electrode is arranged in one-to-one correspondence with the auxiliary structure, and the flexible electrode has the same shape as the auxiliary structure.

6. The neural interface of any one of claims 1-4, wherein, At least one slit is arranged on the flexible electrode, when at least two slits are arranged on the flexible electrode, the slits are arranged at intervals along the length direction of the flexible electrode, the adjacent two slits are arranged staggeredly, and the slits are perpendicular or inclined to the length direction of the flexible electrode.

7. The neural interface of any one of claims 1-4, wherein, ​

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