Annular three-dimensional cortical electrode integrated with nerve stimulation tool, preparation method and electrode array

Abstract

The invention provides an annular three-dimensional cortical electrode integrated with a nerve stimulation tool, a preparation method and an electrode array. The electrode comprises a soft elastic silica gel substrate, an electrode point and a nerve stimulation tool, wherein the silica gel substrate comprises a plane base and a cylindrical boss which extends vertically. In the electrode points, the strip-shaped electrode arms and the annular electrode contacts are attached to the silica gel substrate after being attached to the flexible substrate layer, the electrode contacts are located on the bottom face of the boss, and the electrode arms axially extend to the base along the circumferential wall of the boss. The nerve stimulation tool is inserted into the through hole at the electrode contact and is fixed to the silica gel substrate through the sealing silica gel. By using the electrode, the soft elastic silica gel cylindrical boss with the annular electrode contact can be in elastic deformation contact with the surface of the cerebral cortex groove, so that the soft elastic silica gel cylindrical boss is tightly attached to the cerebral cortex; nerve stimulation tools with different functions can be inserted into the single electrode, so that the cortical electrode and the stimulation electrode are synergistically integrated; meanwhile, the elastic deformation of the soft and elastic silica gel boss is beneficial for controlling the depth of the nerve stimulation tool penetrating into the cerebral cortex.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomedical electronics, and particularly relates to an annular three-dimensional cortical electrode integrating a nerve stimulation tool, a preparation method of the annular three-dimensional cortical electrode, and an electrode array including the annular three-dimensional cortical electrode. Background Art

[0002] The integration of microelectromechanical system (MEMS) technology and flexible electronics technology has laid a solid foundation for the development of high-precision and high-flexibility brain science research tools. Implantable flexible cortical electrodes are important tools for brain science research and brain-computer interface technology. Compared with traditional rigid electrodes, flexible electrodes cause less trauma to brain tissue during implantation and can better maintain adhesion to brain tissue after long-term implantation, thereby improving the stability and accuracy of signal acquisition. In addition, the high-density integration ability of flexible electrodes also enables them to capture finer nerve signals. This high-precision signal acquisition ability is of great significance for analyzing the mechanism of brain nerve circuits, behavior mapping, and decoding of brain-computer interface systems.

[0003] However, how to improve the adhesion performance of the electrode and the multifunctional ability of different types of stimuli while ensuring flexibility is the focus and difficulty of current research on implantable flexible cortical electrodes. In terms of improving the adhesion performance of cortical electrodes, currently, it usually relies on thinning the substrate or using intrinsically flexible materials (such as silicone and hydrogel) to improve flexibility. However, while these methods improve flexibility, they are vulnerable to external force damage due to substrate thinning or insufficient mechanical strength of the material, and the implantation operation difficulty increases. Some studies also adopt mesh or finger-like structure designs to enhance adhesion performance, but such designs cannot meet the reliability requirements in practical applications. At the same time, in existing research, the multifunctional ability is mainly achieved by stacking other functional elements on the electrode. This stacked design often increases the overall thickness and rigidity of the electrode, thereby weakening the adhesion performance between the flexible electrode and the cerebral cortex. In addition, for multifunctional flexible probes, they are prone to deformation and displacement under the influence of external forces during implantation, and there is no support to fix their positions. Therefore, how to improve the precise adhesion performance, stable insertion performance, and multifunctional ability of the electrode while ensuring flexibility has always been a challenge.

[0004] Through a search of the prior art, it was found that Wei Ouyang et al. from the Department of Neurosurgery, Feinberg School of Medicine, Northwestern University, USA, published an article "All-polymeric transient neural probe for prolonged in-vivo electrophysiological recordings" in Biomaterials. In this article, a wireless and battery-free implant for multi-modal closed-loop neuromodulation in small animals was implanted subcutaneously on the back of small animals. Four serpentine wire ends extended from it, and different neuromodulation tools were used at the ends, respectively for autonomously recording electroencephalogram, electromyogram and body temperature, and for closed-loop neuromodulation through optogenetics and pharmacology. The recording electrode consists of a polyimide film, which is double-layer mounted on the surface of a PDMS column (100 nm), and thin films of platinum black (PtBk) and polydopamine (pDA) are formed layer by layer on the bare gold surface. However, the functionality of this electrode is achieved by lateral stacking, which increases the operational complexity and implantation difficulty of the overall structure.

[0005] In addition, the applicant of the present application disclosed a bionic three-dimensional soft and elastic cortical microelectrode and its preparation method in CN115893298A. A claw-shaped structure is provided around the electrode contact. After bending, it can fully wrap and adhere to the soft and elastic silicone boss, so as to ensure that the flexible polymer film microelectrode has both high mechanical strength and conformal contact ability, effectively solving the balance problem between the substrate thickness and conformal attachment ability of the current flexible polymer film microelectrode, and providing an important reference for the development of new minimally invasive implantable brain-computer interface electrodes. However, during the actual use of the microelectrode later, it was found that the electrode only has a single recording function and does not have the ability to perform different stimulations in vivo for a long time. At the same time, its claw-shaped structure is prone to edge warping. Summary of the Invention

[0006] Aiming at the defects and gaps in the prior art, the present invention provides an annular three-dimensional cortical electrode integrated with a nerve stimulation tool, a preparation method of the annular three-dimensional cortical electrode, and an electrode array including the annular three-dimensional cortical electrode, which can ensure the stable insertion of the electrode and its close attachment to the cerebral cortex while realizing the multi-functionality of the electrode, contributing to accurate signal recording and effective electrical stimulation.

[0007] To achieve the above object, the technical solution provided by the present invention is:

[0008] On the one hand, an annular three-dimensional cortical electrode integrated with a nerve stimulation tool is provided, which includes a soft and elastic silicone substrate, electrode points and nerve stimulation tools. The electrode points include an electrode flexible substrate layer, electrode arms, electrode contacts, an electrode flexible encapsulation layer, electrode metal wires and pads;

[0009] The soft and elastic silicone substrate includes a planar base and cylindrical bosses vertically extending from the base; the electrode metal wires and pads are disposed on the electrode flexible substrate layer;

[0010] The electrode contact is annular, the electrode arm is strip-shaped, and one end of the electrode arm is electrically connected to the electrode contact, and the other end is electrically connected to the electrode metal wire; the electrode arm and the electrode contact are attached to the electrode flexible substrate layer on one side surface and then adhered to the soft and elastic silicone substrate. The electrode contact is located at the bottom surface of the boss of the soft and elastic silicone substrate, and the electrode arm axially extends along the circumferential wall of the boss until the base; the electrode arm and the electrode contact are encapsulated by the electrode flexible encapsulation layer on the other side surface;

[0011] A through hole is coaxially formed in the annular three-dimensional cortical electrode within the inner ring edge line of the electrode contact. The nerve stimulation tool is inserted into the through hole and extends out at both ends, and is fixed to the soft and elastic silicone substrate by the sealing silicone.

[0012] Furthermore, a layer of reinforced silicone substrate is provided between the soft and elastic silicone substrate and the electrode flexible substrate layer.

[0013] Furthermore, the nerve stimulation tool can be a probe electrode, an optical fiber, or a drug delivery microneedle.

[0014] Furthermore, the metal layer of the electrode contact is made of gold material and is deposited on the electrode flexible substrate layer by sputtering or thermal evaporation process.

[0015] Furthermore, the diameter of the outer ring of the annular exposed area of the electrode contact is 50 - 500 microns, the diameter of the inner ring is 25 - 250 microns, the thickness of the metal layer is 50 - 300 nanometers, and the diameter of the through hole is 25 - 250 microns.

[0016] Furthermore, the soft and elastic silicone substrate is made of polydimethylsiloxane material.

[0017] Furthermore, the electrode flexible substrate layer uses polyimide as the polymer thin film material and has a thickness of 10 - 50 microns.

[0018] On the other hand, a preparation method of the above-mentioned annular three-dimensional cortical electrode integrated with the nerve stimulation tool is provided, including the following steps:

[0019] In the first step, a planar cortical electrode point including a through hole is fabricated on a silicon wafer deposited with a metal sacrificial layer by MEMS process, wherein the electrode arm and the electrode contact are in the same plane. Then the silicon wafer is immersed in hydrochloric acid solution to release the electrode point from the silicon wafer, and after cleaning and drying the electrode point;

[0020] In the second step, use a silicone mold to align the electrode contact downward and press it into a glass mold with a cylindrical pit against the axis of the pit, so that the electrode flexible encapsulation layers at the electrode contact and the electrode arm are respectively in close contact with the bottom and side surfaces of the pit, thereby obtaining an annular three-dimensional cortical electrode point;

[0021] In the third step, place the glass mold in a high-temperature oven to perform thermal annealing and stress reshaping on the annular three-dimensional cortical electrode point;

[0022] In the fourth step, after completion, pull out the silicone mold from the pit. The three-dimensional cortical electrode point is reshaped by stress into a stress-free three-dimensional form. At this time, the annular three-dimensional cortical electrode point is in close contact with the bottom and side surfaces of the glass mold;

[0023] In the fifth step, inject liquid soft elastic silicone into the pit until it completely levels naturally and fills the groove, and then heat and cure it to form a soft elastic silicone substrate with a boss;

[0024] In the sixth step, after the liquid soft elastic silicone is completely solidified, use a tool to lift the annular three-dimensional cortical electrode to separate it from the glass mold, and obtain an annular three-dimensional cortical electrode point with a soft elastic silicone substrate;

[0025] In the seventh step, use femtosecond laser to coaxially cut the soft elastic silicone substrate inside the inner ring edge line of the electrode contact, so that the soft elastic silicone substrate is completely penetrated to form a through hole with the same diameter as the inner ring edge line;

[0026] In the eighth step, insert the nerve stimulation tool along the axis into the through hole, and use sealing silicone to seal the insertion port of the nerve stimulation tool, thereby obtaining an annular three-dimensional cortical electrode integrated with the nerve stimulation tool.

[0027] On the other hand, there is also provided a preparation method of the above-mentioned annular three-dimensional cortical electrode integrated with the nerve stimulation tool, including the following steps:

[0028] In the first step, use MEMS technology to fabricate a planar cortical electrode point including a through hole on a silicon wafer deposited with a metal sacrificial layer, where the electrode arm and the electrode contact are in the same plane. Then immerse the silicon wafer in hydrochloric acid solution to release the electrode point from the silicon wafer, and then clean and dry the electrode point;

[0029] In the second step, spin-coat a reinforcing silicone substrate with a certain thickness on another silicon wafer with a metal sacrificial layer, and heat it to a semi-cured state;

[0030] In the third step, attach the planar cortical electrode point flatly to the semi-cured reinforcing silicone substrate, and then heat and cure it to make the planar cortical electrode point adhere tightly to the reinforcing silicone substrate;

[0031] In the fourth step, immerse the silicon wafer in hydrochloric acid solution to release the electrode from the silicon wafer, and then clean and dry the electrode;

[0032] In the fifth step, turn over the planar cortical electrode points with the reinforced silicone substrate and perform laser cutting along the hole position gaps of the electrode flexible substrate layer. The cutting depth is the thickness of the reinforced silicone substrate.

[0033] In the sixth step, use a silicone mold to align the electrode contacts of the planar cortical electrode points with the reinforced silicone substrate downward to the center of the concave pit and push them into the glass mold with a cylindrical concave pit, so that the electrode contacts and the electrode flexible encapsulation layers at the electrode arms are closely attached to the bottom and side surfaces of the concave pit respectively, thereby obtaining annular three-dimensional cortical electrode points.

[0034] In the seventh step, place the glass mold in a high-temperature oven to perform thermal annealing and stress reshaping on the annular three-dimensional cortical electrode points.

[0035] In the eighth step, after completion, pull out the silicone mold from the concave pit. The three-dimensional cortical electrode points are reshaped into a stress-free three-dimensional form. At this time, the annular three-dimensional cortical electrode points are closely attached to the bottom and side surfaces of the glass mold.

[0036] In the ninth step, inject liquid soft elastic silicone into the concave pit until it completely levels naturally and fills the groove, and then heat and cure it to form a soft elastic silicone substrate with a boss.

[0037] In the tenth step, after the liquid soft elastic silicone is completely solidified, use a tool to lift the annular three-dimensional cortical electrode to separate it from the glass mold, and obtain annular three-dimensional cortical electrode points with a soft elastic silicone substrate.

[0038] In the eleventh step, use femtosecond laser to perform coaxial cutting inside the inner ring border line of the electrode contact, so that the soft elastic silicone substrate and the reinforced silicone substrate are completely penetrated to form a through hole with the same diameter as the inner ring border line.

[0039] In the twelfth step, insert the nerve stimulation tool along the axis into the through hole, and use sealing silicone to seal the insertion port of the nerve stimulation tool, thereby obtaining an annular three-dimensional cortical electrode integrated with the nerve stimulation tool.

[0040] On the other hand, an electrode array including the above-mentioned annular three-dimensional cortical electrode integrated with the nerve stimulation tool is provided. A plurality of electrode points are arranged in the electrode array, and a plurality of nerve stimulation tools with different functions are inserted into the through holes of each electrode point.

[0041] The advantages of the present invention are:

[0042] 1. The annular three-dimensional cortical electrode integrating a neural stimulation tool proposed by the present invention. The soft and elastic silicone substrate includes a planar base and a cylindrical boss. An annular electrode contact is provided at the bottom surface of the boss. The electrode arm connected to the electrode contact extends from the bottom surface of the boss of the soft and elastic silicone substrate along the side wall perpendicular to the bottom surface to the base, thus forming an annular three-dimensional cortical electrode. Thus, the soft and elastic silicone cylindrical boss with an annular electrode contact can form an elastic deformation contact with the surface of the cerebral cortical sulci, so as to closely adhere to the cerebral cortex, which is beneficial to realizing accurate neural signal acquisition.

[0043] 2. The electrode is provided with a through hole in the boss, and neural stimulation tools with different functions can be inserted therein, so that the cortical electrode and the stimulating electrode can be synergistically integrated, and seamless integration of signal acquisition and a multi-functional stimulation tool can be realized in a single electrode, which not only avoids the damage to the adhesion performance caused by the traditional stacked design, but also significantly improves the versatility and applicability of the electrode.

[0044] 3. The elastic deformation of the soft and elastic silicone boss helps to control the depth of the neural stimulation tool inserted into the cerebral cortex. The fixing effect it plays makes the inserted neural stimulation tool not easily shift and deform, and the depth of insertion into a specific area can be accurately controlled and adjusted, realizing a more stable and effective electrical stimulation function.

[0045] 4. In the present invention, a layer of reinforced silicone substrate is provided between the soft and elastic silicone substrate and the flexible electrode substrate layer, which can avoid the problem of electrode point failure caused by the easy flow of liquid soft and elastic silicone into the electrode contact during the preparation of the electrode.

[0046] 5. A plurality of electrode points are arranged in the electrode array of the present invention, and a plurality of neural stimulation tools with different functions can be inserted into the through holes in each electrode point according to needs, realizing the integration of multi-functional stimulation of the electrode. BRIEF DESCRIPTION OF THE DRAWINGS

[0047] Through the following description with reference to the drawings, the above and / or other features and advantages of the present invention will become more easily understood. The drawings are not drawn to scale, and some features are enlarged or reduced to show the details of specific components. In the drawings:

[0048] Figure 1 is a cross-sectional structural schematic diagram of the annular three-dimensional cortical electrode integrating a neural stimulation tool of the present invention;

[0049] Figure 2 is a three-dimensional attachment schematic diagram of the annular three-dimensional cortical electrode of the present invention on the surface of the cerebral cortex during use;

[0050] Figure 3 is a schematic diagram of the preparation process of the annular three-dimensional cortical electrode of the present invention Figure 1 ;

[0051] Figure 4 Schematic of the preparation process of the annular three-dimensional cortical electrode of the present invention Figure 2 ;

[0052] Figure 5 Schematic diagram of the three-dimensional structure of the electrode array of the annular three-dimensional cortical electrode of the present invention

[0053] In the figure: 1-soft elastic silicone substrate, 11-substrate, 12-boss; 2-electrode flexible substrate layer; 3-electrode arm; 4-electrode contact; 5-electrode flexible encapsulation layer; 6-nerve stimulation tool; 7-through hole; 8-sealing silicone; 9-annular three-dimensional cortical electrode; 10-cerebral cortex; 11-microneedle electrode; 12-optical fiber; 13-drug delivery microneedle Specific embodiments

[0054] The present invention will be described in detail below with reference to the accompanying drawings by means of exemplary embodiments of the present invention. It should be noted that the following detailed description of the present invention is for illustrative purposes only and does not limit the present invention

[0055] The present invention provides an annular three-dimensional cortical electrode integrated with a nerve stimulation tool, a preparation method of the annular three-dimensional cortical electrode, and an electrode array including the annular three-dimensional cortical electrode. The annular three-dimensional cortical electrode can be stably inserted into the brain tissue, closely adhere to the cerebral cortex, and simultaneously achieve the multifunctional ability of different types of stimulation

[0056] First, the annular three-dimensional cortical electrode integrated with a nerve stimulation tool provided by the present invention will be described in detail

[0057] Refer to Figure 1 and Figure 2 , the annular three-dimensional cortical electrode integrated with a nerve stimulation tool of the present invention includes a soft elastic silicone substrate 1 and electrode points for collecting nerve signals. The electrode points include an electrode flexible substrate layer 2, an electrode arm 3, an electrode contact 4, an electrode flexible encapsulation layer 5, electrode metal wires and pads (not marked in the figure). The annular three-dimensional cortical electrode further includes a nerve stimulation tool 6 for performing nerve stimulation

[0058] The soft elastic silicone substrate 1 includes a planar substrate 11 and a cylindrical boss 12 vertically extending from the substrate 11. The soft elastic silicone substrate 1 can be made of polydimethylsiloxane (PDMS) material. The electrode flexible substrate layer 2 can use polyimide (PI) as the polymer film material and has a thickness of 10-50 microns. The electrode metal wires and pads are arranged on the electrode flexible substrate layer 2. In particular, the electrode metal wires are arranged inside the flexible substrate, and the pads are arranged on the surface of the flexible substrate

[0059] The electrode contact 4 is in a circular ring shape, the electrode arm 3 is in a strip shape, and one end of the electrode arm 3 is electrically connected to the electrode contact 4, and the other end is electrically connected to the electrode metal wire. The electrode arm 3 and the electrode contact 4 are attached to the soft elastic silicone substrate 1 after being attached to the electrode flexible substrate layer 2 on one side end surface. Optionally, the metal layer of the electrode contact 4 is made of gold material and is deposited on the electrode flexible substrate layer 2 by sputtering or thermal evaporation process.

[0060] The electrode contact 4 is located at the bottom surface of the convex platform 12 of the soft elastic silicone substrate 1, and the electrode arm 3 axially extends along the circumferential wall of the convex platform 12 until it reaches the base 11. In other words, the electrode arm 3 extends perpendicular to the bottom surface of the convex platform and the electrode contact 4 thereon and adheres to the base 11. Therefore, the cortical electrode proposed by the present invention is an annular three-dimensional cortical electrode, and the soft elastic silicone cylindrical convex platform with an annular electrode contact can form elastic deformation contact with the surface of the cerebral cortical sulci, so as to closely adhere to the cerebral cortex, which is beneficial to realizing accurate nerve signal acquisition.

[0061] The electrode arm 3 and the electrode contact 4 are encapsulated by the electrode flexible encapsulation layer 5 on the other side end surface. It should be understood that as mentioned above, the electrode contact 4 is encapsulated inside the inner ring side line and outside the outer ring side line, exposing an annular area for signal acquisition. In a specific embodiment of the present invention, the diameter of the outer ring of the annular exposed area of the electrode contact 4 is 50 - 500 microns, the diameter of the inner ring is 25 - 250 microns, the thickness of the metal layer is 50 - 300 nanometers, and the diameter of the through hole 7 is 25 - 250 microns.

[0062] A circular through hole 7 is coaxially arranged through the annular three-dimensional cortical electrode inside the inner ring side line of the electrode contact 4. Preferably, the through hole 7 is located in the middle of the convex platform 12. The nerve stimulation tool 6 is inserted into the through hole 7 and extends out at both ends, and is fixed to the soft elastic silicone substrate 1 through the sealing silicone 8, especially biocompatible sealing silicone. The nerve stimulation tool 6 can be selected as a probe electrode, an optical fiber, a drug delivery micro needle, etc. according to needs to realize different functions of stimulation. Thus, the cortical electrode and the stimulation electrode can be synergistically integrated, and the seamless integration of signal acquisition and a multi-functional stimulation tool can be realized in a single electrode, which not only avoids the damage to the attachment performance of the traditional stacked design, but also significantly improves the multi-functionality and applicability of the electrode.

[0063] Using the annular three-dimensional cortical electrode integrated with the nerve stimulation tool of the present invention, the elastic deformation of the soft elastic silicone convex platform helps to control the depth of the nerve stimulation tool inserted into the cerebral cortex. Its fixing effect makes the inserted nerve stimulation tool not easily shift and deform, and the depth of insertion into a specific area can be accurately controlled and adjusted to realize a more stable and effective electrical stimulation function.

[0064] As Figure 2As shown in the figure, the three-dimensional attachment of the annular three-dimensional cortical electrode 9 of the present invention on the surface of the cerebral cortex 10 is such that the soft elastic silicone below the microelectrode can deform to a depth of 600 microns after contact. The cortical electrode can form an elastic deformation contact relationship with the surface of the cerebral cortex gyrus using the deformation ability of the silicone. Among them, the electrode contacts can be closely attached to the cortical surface under extrusion, and the nerve stimulation tool can be stably inserted into a specific area with a fixed depth under the fixing action of the soft elastic silicone boss, which can not only accurately and stably record electroencephalogram signals but also achieve effective and diverse electrical stimulations.

[0065] Next, a detailed description will be given to the preparation method of the above-mentioned annular three-dimensional cortical electrode of the integrated nerve stimulation tool provided by the present invention.

[0066] Refer to Figure 3 , the preparation method of an embodiment of the present invention includes the following steps:

[0067] Step S1, using MEMS technology to fabricate a planar cortical electrode point including a through hole on a silicon wafer deposited with a metal sacrificial layer, where the strip-shaped electrode arm and the annular electrode contact are in the same plane, and a through hole is opened inside the inner ring border line of the annular electrode contact. Then, the silicon wafer is immersed in hydrochloric acid solution to release the electrode point from the silicon wafer, and after cleaning the electrode point, it is dried;

[0068] Step S2, using a silicone mold to push the electrode contact downward and align it with the center of the concave pit into a glass mold with a cylindrical concave pit, so that the electrode flexible encapsulation layers at the electrode contact and the electrode arm are closely attached to the bottom surface and the side surface of the concave pit respectively, thereby obtaining an annular three-dimensional cortical electrode point; in this regard, those skilled in the art will understand that if there are multiple electrode points, in step S1, circular gaps slightly larger than the outer ring border line diameter of the electrode contact and annular gaps slightly larger than the outer dimension of the electrode arm are opened at the corresponding electrode sites on the integral electrode flexible substrate layer, so that in this step S2, when the silicone mold presses the electrode contact, the electrode contact and the electrode arm are lifted relative to the electrode plane and the electrode contact is no longer in the same plane as the electrode arm;

[0069] Step S3, placing the glass mold in a high-temperature oven to perform thermal annealing and stress reshaping on the annular three-dimensional cortical electrode point;

[0070] Step S4, after completion, pulling out the silicone mold from the concave pit, the three-dimensional cortical electrode point is reshaped into a stress-free three-dimensional form by stress, and at this time, the annular three-dimensional cortical electrode point is closely attached to the bottom and side surfaces of the glass mold;

[0071] Step S5, injecting liquid soft elastic silicone at the concave pit until it completely levels naturally and fills the groove, and then heating and curing to form a soft elastic silicone substrate with a boss;

[0072] Step S6, after the liquid soft elastic silicone is completely solidified, use a tool to lift the annular three-dimensional cortical electrode to separate it from the glass mold, obtaining an annular three-dimensional cortical electrode point with a soft elastic silicone substrate;

[0073] Step S7, use femtosecond laser to coaxially cut the soft elastic silicone substrate within the inner ring border of the electrode contact, so that the soft elastic silicone substrate is completely penetrated to form a through hole with the same diameter as the inner ring border;

[0074] Step S8, insert the nerve stimulation tool along the axis into the through hole, and use sealing silicone to seal the insertion opening of the nerve stimulation tool, thereby obtaining an annular three-dimensional cortical electrode integrated with the nerve stimulation tool.

[0075] This embodiment can be specifically implemented through the following steps:

[0076] Step (a), use MEMS process to fabricate a planar cortical electrode point based on PI material on a silicon wafer deposited with a metal sacrificial layer; then, immerse the 4-inch silicon wafer in 3% hydrochloric acid solution for 12 - 15 h to release the cortical electrode point from the silicon wafer; finally, clean the cortical electrode point and dry it in an oven at 35 °C for 15 minutes; in this electrode point, the outer diameter of the electrode contact is 400 microns, the inner diameter is 200 microns, the metal layer thickness is 200 nanometers, the PI layer thickness is 10 microns, the electrode arm length is 700 microns, and the width is 320 microns;

[0077] Step (b), use a silicone mold with the same shape and pit to align the electrode contact downward and push it into a glass mold with a cylindrical pit along the pit axis, so that the electrode flexible encapsulation layers at the electrode contact and the electrode arm are respectively in close contact with the bottom and side surfaces of the pit, where the depth of the pit is 660 microns, thereby obtaining an annular three-dimensional cortical electrode point;

[0078] Step (c), place the glass mold in a high-temperature oven (180 °C, 24 h) to perform thermal annealing and stress reshaping on the electrode point;

[0079] Step (d), after completion, gently pull out the silicone mold from the pit. The three-dimensional electrode point is reshaped by stress into a stress-free three-dimensional form. At this time, the annular three-dimensional cortical electrode point is in close contact with the bottom and side surfaces of the glass mold;

[0080] Step (e), slowly inject liquid soft elastic silicone PDMS at the pit until it completely levels naturally and fills the groove, and then heat and cure it at 85 °C for 5 h to form a soft elastic silicone substrate with a boss;

[0081] Step (f), wait until the liquid soft elastic silicone PDMS is completely solidified, and then gently lift the annular three-dimensional cortical electrode with tweezers to separate it from the glass mold, obtaining an annular three-dimensional cortical electrode point with a soft elastic silicone substrate;

[0082] Step (g): Use a femtosecond laser to cut along the inner ring edge of the annular three-dimensional cortical electrode contact at a power of 20 W, so that the soft elastic silicone substrate is completely penetrated to form a laser through-hole with a diameter of 200 microns.

[0083] Step (h): Insert nerve stimulation tools with different functions along the axis into the laser through-hole, and use biocompatible sealing silicone to seal the insertion openings of the nerve stimulation tools.

[0084] To make up for the deficiency that PDMS easily flows into the electrode contacts in step (e), a cured PDMS layer can be added between the soft elastic silicone substrate and the electrode flexible substrate layer as a reinforced silicone substrate to prevent the failure of the electrode points.

[0085] Regarding this, refer to Figure 4 , the preparation method as another embodiment of the present invention includes the following steps:

[0086] Step S1: Use MEMS technology to fabricate planar cortical electrode points including through-holes on a silicon wafer deposited with a metal sacrificial layer, where the strip-shaped electrode arms and the annular electrode contacts are in the same plane, and a through-hole is opened inside the inner ring edge of the annular electrode. Then, immerse the silicon wafer in hydrochloric acid solution to release the electrode points from the silicon wafer, and then clean and dry the electrode points.

[0087] Step S2: Spin-coat a certain thickness of reinforced silicone substrate on another silicon wafer with a metal sacrificial layer, and heat it to a semi-cured state.

[0088] Step S3: Flatly attach the planar cortical electrode points to the semi-cured reinforced silicone substrate, and then heat and cure them to make the planar cortical electrode points tightly adhere to the reinforced silicone substrate.

[0089] Step S4: Immerse the silicon wafer in hydrochloric acid solution to release the electrodes from the silicon wafer, and then clean and dry the electrodes.

[0090] Step S5: Flip the planar cortical electrode points with the reinforced silicone substrate, and perform laser cutting along the hole position gaps of the electrode flexible substrate layer. The cutting depth is the thickness of the reinforced silicone substrate.

[0091] Step S6: Use a silicone mold to align the electrode contacts of the planar cortical electrode points with the reinforced silicone substrate downward and push them into a glass mold with a cylindrical pit along the axis of the pit, so that the electrode flexible encapsulation layers at the electrode contacts and the electrode arms are respectively in close contact with the bottom and side surfaces of the pit, thereby obtaining annular three-dimensional cortical electrode points.

[0092] Step S7: Place the glass mold in a high-temperature oven to perform thermal annealing and stress reshaping on the annular three-dimensional cortical electrode points.

[0093] Step S8, after completion, pull out the silicone mold from the pit. The three-dimensional cortical electrode points are reshaped into a stress-free three-dimensional form by stress. At this time, the annular three-dimensional cortical electrode points are closely attached to the bottom and side of the glass mold.

[0094] Step S9, inject liquid soft elastic silicone into the pit until it completely levels off naturally and fills the groove, and then heat and cure it to form a soft elastic silicone substrate with a boss. At this time, the soft elastic silicone substrate will not flow into the position of the electrode contact due to the blocking effect of the cured reinforced silicone substrate.

[0095] Step S10, after the liquid soft elastic silicone is completely solidified, use a tool to lift the annular three-dimensional cortical electrode to separate it from the glass mold, and obtain an annular three-dimensional cortical electrode point with a soft elastic silicone substrate.

[0096] Step S11, use femtosecond laser to cut coaxially inside the inner ring edge line of the electrode contact, so that the soft elastic silicone substrate and the reinforced silicone substrate are completely penetrated to form a through hole with the same diameter as the inner ring edge line.

[0097] Step S12, insert the nerve stimulation tool along the axis into the through hole, and use sealing silicone to seal the insertion port of the nerve stimulation tool, so as to obtain an annular three-dimensional cortical electrode integrated with the nerve stimulation tool.

[0098] This embodiment can be specifically implemented through the following steps:

[0099] Step (a), first fabricate a planar cortical electrode point based on PI material on a silicon wafer deposited with a metal sacrificial layer by MEMS process; then immerse the silicon wafer in 3% hydrochloric acid solution for 12 - 15 h to release the cortical electrode from the silicon wafer; finally, clean the cortical electrode and dry it in an oven at 35 °C for 15 minutes; here, the outer diameter of the electrode contact is 400 microns, the inner diameter is 200 microns, the metal layer thickness is 200 nm, the PI layer thickness is 10 microns, the electrode arm length is 700 microns, and the width is 320 microns.

[0100] Step (b), spin-coat a certain thickness of PDMS on another silicon wafer with a metal sacrificial layer, and heat it at 60 °C for 1 h to become semi-cured.

[0101] Step (c), flatly attach the planar cortical electrode point to the semi-cured PDMS, and then heat it at 85 °C for 5 h until the PDMS is cured, so that the electrode point is tightly adhered to the PDMS.

[0102] Step (d), immerse the silicon wafer in 3% hydrochloric acid solution for 12 - 15 h to release the planar cortical electrode point from the silicon wafer, then clean the electrode point and dry it in an oven at 35 °C for 15 minutes.

[0103] Step (e): Flip the planar cortical electrode points with the PDMS substrate and perform laser cutting along the hole position gaps of the PI substrate layer. The cutting depth is the thickness of the PDMS substrate.

[0104] Step (f): Use a silicone mold with the same shape and pits to align the electrode contacts of the planar cortical electrode points with the PDMS substrate downward to the center of the pit axis and press them into a glass mold with cylindrical pits, so that the electrode contacts and the electrode flexible encapsulation layers at the electrode arms are closely attached to the bottom and side surfaces of the pits respectively. The depth of the pits is 660 microns, thereby obtaining annular three-dimensional cortical electrode points.

[0105] Step (g): Place the glass mold in a high-temperature oven (180 °C, 24 h) to perform thermal annealing and stress reshaping on the annular three-dimensional cortical electrode points.

[0106] Step (h): After completion, gently pull out the silicone mold from the pits. The three-dimensional cortical electrode points are reshaped by stress into a stress-free three-dimensional form.

[0107] Step (i): Slowly inject liquid soft elastic silicone PDMS into the pits until it completely levels naturally and fills the grooves, and then heat and cure it at 85 °C for 5 h to form a soft elastic silicone substrate with a boss. At this time, PDMS will not flow into the electrode contact position due to the blocking effect of the cured PDMS substrate.

[0108] Step (j): Wait for the liquid soft elastic silicone PDMS to completely solidify, and then gently lift the annular three-dimensional cortical electrode with tweezers to separate it from the glass mold to obtain annular three-dimensional cortical electrode points with a soft elastic silicone substrate.

[0109] Step (k): Use femtosecond laser to cut along the inner ring edge line of the electrode contact with a power of 20 w, so that the soft elastic silicone substrate and the reinforced silicone substrate are completely penetrated to form a laser through-hole with a diameter of 200 microns.

[0110] Step (l): Insert different functional nerve stimulation tools along the axis into the laser through-holes, and use biocompatible sealing silicone to seal the insertion ports of the nerve stimulation tools, thereby obtaining an annular three-dimensional cortical electrode integrated with nerve stimulation tools.

[0111] Next, the electrode array of the annular three-dimensional cortical electrode including the above integrated nerve stimulation tools provided by the present invention will be described in detail.

[0112] Refer to Figure 5 , the electrode array is designed to achieve various stimulation effects, in which multiple electrode points are arranged, and different functional multiple nerve stimulation tools are inserted into the through-holes of each electrode point, including micro-needle electrodes 11, optical fibers 12 and drug delivery micro-needles 13, which can provide customized solutions for different neuroscience research and clinical application requirements.

[0113] Specifically, the microneedle electrode 11 penetrates the tissue in a minimally invasive manner, capable of precisely delivering electrical stimulation to the target area, achieving electrical stimulation with high spatiotemporal resolution while reducing damage to the surrounding tissue. In addition, the microneedle electrode 11 can also be used to record electrophysiological signals, providing support for the monitoring of neural activities. The optical fiber 12 is used to achieve optical stimulation. By transmitting light of a specific wavelength through the optical fiber, photosensitive proteins can be activated or optogenetic responses can be triggered, thereby achieving precise regulation of neuronal activities. This optical stimulation method combines the high light conductivity and biocompatibility of the optical fiber, enabling long-term stable stimulation. In addition, the drug delivery microneedle 13 can achieve drug stimulation. This microneedle can directly deliver drugs to the target tissue, increasing the local concentration of the drug while reducing systemic side effects. The drug delivery microneedle 13 allows the drug to be released under specific stimuli, such as triggering drug release through electrical stimulation or optical stimulation, thereby achieving spatiotemporally controllable drug delivery. These three types of stimulations are applicable to different scenarios, and different structures of stimulating electrodes are required according to different needs. The integrated annular three-dimensional cortical electrode and the electrode array of different nerve stimulation tools demonstrate the advantage of combining different stimulation functions on a single electrode, eliminating the need to redesign the electrode and implant it each time, and realizing the integration of multi-functional stimulation of the electrode.

[0114] By integrating the microneedle electrode 11, the optical fiber 12, and the drug delivery microneedle 13 into the annular three-dimensional cortical electrode, not only can the synergistic effect of electrical stimulation, optical stimulation, and drug stimulation be achieved, but also the stimulation method and intensity can be adjusted according to different application scenarios.

[0115] Regarding the preparation of this electrode array, Figure 3 the bosses of the soft and elastic silicone substrate in step (e) are uniformly arranged bosses on one layer of the soft and elastic silicone substrate. Specifically, after the electrode arm, the electrode contact, and the pit are closely attached, liquid soft and elastic silicone PDMS is injected, and then a certain thickness of the same material silicone is uniformly spin-coated on the back of the annular three-dimensional cortical electrode point using a spin coater. After the silicone is cured, a whole silicone layer with many bosses is formed. Finally, the annular three-dimensional cortical electrode point is gently lifted and separated from the glass mold to obtain an annular three-dimensional cortical electrode point with a silicone substrate and multiple soft and elastic silicone bosses.

[0116] Finally, it should be noted that the features mentioned and / or shown in the above description of the exemplary embodiments of the present invention can be combined in the same or similar manner into one or more other embodiments, combined with the features in other embodiments, or replace the corresponding features in other embodiments. The technical solutions obtained through such combination or replacement should also be regarded as being included within the protection scope of the present invention.

Claims

1. A ring-shaped three-dimensional cortical electrode integrated with a neural stimulation tool, characterized in that: It includes a soft elastic silicone substrate, an electrode point and a nerve stimulation tool, wherein the electrode point includes an electrode flexible substrate layer, an electrode arm, an electrode contact, an electrode flexible packaging layer, an electrode metal wire and a welding pad; The soft elastic silicone substrate comprises a planar base and a cylindrical boss extending vertically from the base; the electrode metal wire and the pad are arranged on the electrode flexible substrate layer; The electrode contact is ring-shaped, the electrode arm is strip-shaped, and one end of the electrode arm is electrically connected to the electrode contact, and the other end is electrically connected to the electrode metal wire; the electrode arm and the electrode contact are adhered to the soft elastic silicone substrate after being bonded to the electrode flexible substrate layer on one end surface, the electrode contact is located at the bottom surface of the boss of the soft elastic silicone substrate, and the electrode arm extends axially along the peripheral wall of the boss to the base; the electrode arm and the electrode contact are encapsulated by the electrode flexible encapsulation layer on the other end surface; A through hole is coaxially provided within the inner ring edge of the electrode contact and passes through the annular three-dimensional cortical electrode. The neural stimulation tool is inserted into the through hole and extends out at both ends and is fixed to the soft elastic silicone substrate through sealing silicone.

2. The annular three-dimensional cortical electrode integrated with a neural stimulation tool according to claim 1, characterized in that: A layer of reinforced silicone substrate is arranged between the soft elastic silicone substrate and the electrode flexible substrate layer.

3. The annular three-dimensional cortical electrode integrated with a neural stimulation tool according to claim 1 or 2, characterized in that: The neural stimulation tool can be a probe electrode, an optical fiber, or a drug delivery microneedle.

4. The annular three-dimensional cortical electrode of the integrated neural stimulation tool according to claim 1 or 2, characterized in that: The metal layer of the electrode contact is a gold material, which is deposited on the electrode flexible substrate layer by sputtering or thermal evaporation process.

5. The annular three-dimensional cortical electrode integrated with a neural stimulation tool according to claim 4, characterized in that: The outer ring diameter of the annular exposed area of ​​the electrode contact is 50-500 microns, the inner ring diameter is 25-250 microns, the thickness of the metal layer is 50-300 nanometers, and the diameter of the through hole is 25-250 microns.

6. The annular three-dimensional cortical electrode integrated with a neural stimulation tool according to claim 1 or 2, characterized in that: The soft elastic silicone substrate is made of polydimethylsiloxane material.

7. The annular three-dimensional cortical electrode integrated with a neural stimulation tool according to claim 1 or 2, characterized in that: The electrode flexible substrate layer uses polyimide as a polymer film material and has a thickness of 10 to 50 microns.

8. A method for preparing a ring-shaped three-dimensional cortical electrode of an integrated neural stimulation tool according to any one of claims 1 to 7, characterized in that: The following steps are involved: In the first step, a planar cortical electrode point including a through hole is made on a silicon wafer with a metal sacrificial layer deposited thereon using a MEMS process, wherein the electrode arm and the electrode contact point are in the same plane, and then the silicon wafer is immersed in a hydrochloric acid solution to release the electrode point from the silicon wafer, and then the electrode point is cleaned and dried; In the second step, the electrode contact is aligned downward with the axis of the pit using a silicone mold and pushed into the glass mold with a cylindrical pit, so that the electrode flexible packaging layer at the electrode contact and the electrode arm is tightly attached to the bottom and side of the pit respectively, thereby obtaining a ring-shaped three-dimensional cortical electrode point; In the third step, the glass mold is placed in a high-temperature oven to perform thermal annealing and stress reshaping on the annular three-dimensional cortical electrode points; Step 4: After completion, the silicone mold is pulled out of the pit, and the three-dimensional cortical electrode point is reshaped into a stress-free three-dimensional shape by stress. At this time, the annular three-dimensional cortical electrode point is tightly attached to the bottom and side of the glass mold; Step 5: inject liquid soft elastic silicone into the pit until it is completely naturally leveled and fills the groove, and then heats and solidifies to form a soft elastic silicone substrate with a boss; Step 6: After the liquid soft elastic silicone is completely solidified, use a tool to lift the annular three-dimensional cortical electrode to separate it from the glass mold, thereby obtaining an annular three-dimensional cortical electrode point with a soft elastic silicone substrate; Step 7: Use a femtosecond laser to coaxially cut the soft elastic silicone substrate within the inner ring edge of the electrode contact, so that the soft elastic silicone substrate is completely opened to form a through hole with the same diameter as the inner ring edge; In the eighth step, the neural stimulation tool is inserted into the through hole along the axis, and the insertion port of the neural stimulation tool is sealed with sealing silicone, thereby obtaining a ring-shaped three-dimensional cortical electrode integrated with the neural stimulation tool.

9. A method for preparing a ring-shaped three-dimensional cortical electrode of an integrated neural stimulation tool according to any one of claims 2 to 7, characterized in that: The following steps are involved: In the first step, a planar cortical electrode point including a through hole is made on a silicon wafer with a metal sacrificial layer deposited thereon using a MEMS process, wherein the electrode arm and the electrode contact point are in the same plane, and then the silicon wafer is immersed in a hydrochloric acid solution to release the electrode point from the silicon wafer, and then the electrode point is cleaned and dried; In the second step, a reinforced silicone substrate of a certain thickness is spin-coated on another silicon wafer with a metal sacrificial layer, and heated to make it semi-cured; The third step is to flatly attach the planar cortical electrode points to the semi-cured reinforced silicone substrate, and then heat and cure them so that the planar cortical electrode points are tightly adhered to the reinforced silicone substrate; The fourth step is to immerse the silicon wafer in a hydrochloric acid solution to release the electrode from the silicon wafer, and then clean and dry the electrode; Step 5: Flip the flat cortical electrode with the reinforced silicone substrate over and perform laser cutting along the hole gap of the flexible substrate layer of the electrode. The cutting depth is the thickness of the reinforced silicone substrate. Step 6: Use a silicone mold to align the electrode contact of the flat cortical electrode point with a reinforced silicone substrate downwardly with the axis of the pit and push it into the glass mold with a cylindrical pit, so that the electrode contact and the electrode flexible packaging layer at the electrode arm are closely attached to the bottom and side of the pit respectively, thereby obtaining a ring-shaped three-dimensional cortical electrode point; Step 7: Place the glass mold in a high-temperature oven to perform thermal annealing and stress reshaping on the annular three-dimensional cortical electrode points; Step 8. After completion, the silicone mold is pulled out of the pit, and the three-dimensional cortical electrode point is reshaped into a stress-free three-dimensional shape by stress. At this time, the annular three-dimensional cortical electrode point is tightly attached to the bottom and side of the glass mold; Step 9: inject liquid soft elastic silicone into the pit until it is completely naturally leveled and fills the groove, and then heats and solidifies to form a soft elastic silicone substrate with a boss; Step 10: After the liquid soft elastic silicone is completely solidified, use a tool to lift the annular three-dimensional cortical electrode to separate it from the glass mold, thereby obtaining an annular three-dimensional cortical electrode point with a soft elastic silicone substrate; Step 11: Using a femtosecond laser to coaxially cut inside the inner ring edge of the electrode contact, the soft elastic silicone substrate and the reinforced silicone substrate are completely opened to form a through hole with the same diameter as the inner ring edge; In the twelfth step, the neural stimulation tool is inserted into the through hole along the axis, and the insertion port of the neural stimulation tool is sealed with sealing silicone, thereby obtaining a ring-shaped three-dimensional cortical electrode integrated with the neural stimulation tool.

10. An electrode array comprising a ring-shaped three-dimensional cortical electrode of an integrated neural stimulation tool according to any one of claims 1 to 7, characterized in that: A plurality of electrode points are arranged in the electrode array, and a plurality of nerve stimulation tools with different functions are inserted into the through holes in the respective electrode points.

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