A flexible electrode for spinal cord and its manufacturing method
By designing a multi-layered flexible electrode and using biocompatible materials and wires for connection, the shortcomings of existing spinal nerve electrodes in recording and stimulation accuracy have been overcome. This has enabled high spatial resolution signal recording and precise nerve stimulation, while improving the stability and lifespan of the electrode.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2022-06-17
- Publication Date
- 2026-03-10
AI Technical Summary
Existing spinal nerve electrodes have shortcomings in recording and stimulation accuracy. Epidural electrodes have low spatial resolution, and intraspinal electrodes have a limited number of channels and are made of rigid materials, making them prone to breakage and unable to record neuronal activity stably for a long time.
A flexible electrode was designed, comprising an attachment part and an implantation part, employing a multi-layer structure. It uses biocompatible insulating layers such as polyimide and polydimethylsiloxane, and the lead wire layer is made of materials such as titanium and gold. The electrode sites are connected to the lead wires through through holes, and the rear part can be integrated with the rear circuit to achieve high spatial resolution signal recording and stimulation.
It achieves high spatial resolution signal recording and precise nerve stimulation. The flexible electrode can adapt to the deformation of the spinal cord, improving the stability and long service life of the electrode.
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Figure CN115054260B_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The present disclosure relates to the technical field of life science, and more particularly to a flexible electrode for spinal cord and a manufacturing method thereof. BACKGROUND
[0002] Spinal cord electrodes include epidural electrodes and intraspinal electrodes. SUMMARY
[0003] A brief summary of the present disclosure is presented in the following for the purpose of providing a basic understanding of some aspects of the present disclosure. However, this summary is not an extensive overview of the present disclosure. It is not intended to identify key or critical elements of the present disclosure or to delineate the scope of the present disclosure. Its sole purpose is to present some concepts of the present disclosure in a simplified form as a prelude to the more detailed description that is presented later.
[0004] According to a first aspect of the present disclosure, there is provided a flexible electrode for spinal cord, the flexible electrode comprising: an attaching portion configured to be able to be outside the white matter epidurally or intradurally, and configured to collect or apply an electrical signal on the surface of the spinal cord; wherein the attaching portion of the flexible electrode comprises a first insulating layer and a second insulating layer and a wire layer between the first insulating layer and the second insulating layer; wherein the attaching portion of the flexible electrode further comprises one or more electrode sites, each electrode site being electrically coupled to one of the wires in the wire layer and being in contact with the spinal cord after implantation of the flexible electrode to collect an electrical signal from the spinal cord nerve and transmit the collected electrical signal through the wire, or to apply an electrical signal received through the wire to the spinal cord nerve.
[0005] According to a second aspect of the present disclosure, there is provided a manufacturing method of a flexible electrode for spinal cord, the flexible electrode being the flexible electrode according to the first aspect of the present disclosure, the method comprising: manufacturing a first insulating layer, a wire layer, a second insulating layer and an electrode site on a substrate; and separating the flexible electrode from the substrate; wherein a through hole is manufactured in at least one of the first insulating layer and the second insulating layer at a position corresponding to the electrode site by patterning.
[0006] Other features of the present disclosure, and its advantages, will become apparent in the following detailed description of exemplary embodiments of the present disclosure, with reference to the drawings. BRIEF DESCRIPTION OF DRAWINGS
[0007] The accompanying drawings, which constitute a part of this specification, illustrate embodiments of the present disclosure and, together with the description, serve to explain the principles of the present disclosure.
[0008] This disclosure will be more clearly understood with reference to the accompanying drawings and the following detailed description, wherein:
[0009] Figure 1 A schematic diagram of at least a portion of a flexible electrode for the spinal cord according to an embodiment of the present disclosure is shown;
[0010] Figure 2 A schematic diagram illustrating an implantation method of at least a portion of a flexible electrode for the spinal cord according to an embodiment of the present disclosure is shown.
[0011] Figure 3 An exploded view of at least a portion of a flexible electrode according to an embodiment of the present disclosure is shown;
[0012] Figure 4 A flowchart illustrating a method for manufacturing a flexible electrode according to an embodiment of the present disclosure is shown;
[0013] Figure 5 A schematic diagram of a method for manufacturing a flexible electrode according to an embodiment of the present disclosure is shown;
[0014] Figure 6 A schematic diagram of a method for manufacturing a flexible electrode according to an embodiment of the present disclosure is shown;
[0015] Figure 7 A schematic diagram of a method for manufacturing a flexible electrode according to an embodiment of the present disclosure is shown. Detailed Implementation
[0016] The following detailed description is based on the accompanying drawings and provides various exemplary embodiments of the present disclosure to aid in a comprehensive understanding. Various details are included in the following description to aid understanding; however, these details are considered exemplary only and not intended to limit the present disclosure, which is defined by the appended claims and their equivalents. The words and phrases used in the following description are intended only to provide a clear and consistent understanding of the present disclosure. Additionally, descriptions of well-known structures, functions, and configurations may have been omitted for clarity and brevity. Those skilled in the art will recognize that various changes and modifications can be made to the examples described herein without departing from the spirit and scope of the present disclosure.
[0017] The following description of at least one exemplary embodiment is merely illustrative and is in no way intended to limit the scope of this disclosure or its application or use. That is, the structures and methods herein are shown in an exemplary manner to illustrate different embodiments of the structures and methods in this disclosure. However, those skilled in the art will understand that they merely illustrate exemplary ways that can be used to implement this disclosure, and not exhaustive ways. Furthermore, the drawings are not necessarily drawn to scale, and some features may be enlarged to show details of specific components.
[0018] Techniques, methods, and equipment known to those skilled in the art may not be discussed in detail, but where appropriate, such techniques, methods, and equipment should be considered part of the specification.
[0019] In all examples shown and discussed herein, any specific values should be interpreted as merely exemplary and not as limitations. Therefore, other examples of exemplary embodiments may have different values.
[0020] Compared to spinal electrodes, epidural electrodes can only record local field potentials (LFP) signals due to their less-than-ideal spatial resolution. In contrast, spinal electrodes utilize higher spatial precision and can simultaneously record LFP and single neuronal spike signals. However, current spinal electrodes also face various challenges. Electrodes with a low channel count are limited by the number of neurons they can record, making it impossible to fully utilize their spatial resolution for motor decoding and fine limb manipulation. In addition to channel counting, when electrodes are implanted in the repeatedly deforming spinal cord, the physical brittleness caused by the stiffness of the electrode material may cause the electrodes to break during electrical interface and real-time decoding, resulting in unstable long-term recording. As for stimulation, the stimulation precision is low, only stimulating nerve bundles and being far from motor nerves.
[0021] Figure 1 A schematic diagram of at least a portion of a flexible electrode 100 for the spinal cord according to an embodiment of the present disclosure is shown. Figure 1As shown, the flexible electrode 100 may include an attachment portion 110, which may be configured to be located on the white matter outside the epidural space or within the epidural space, and configured to acquire or apply electrical signals to the surface of the spinal cord. The flexible electrode 100 may also include one or more implantation portions 120, which are arranged symmetrically or asymmetrically, each extending from the attachment portion, and may be configured to be implanted into the spinal cord or into neural tissue (such as nerve roots, ganglia, etc.) connected to the spinal cord, and configured to acquire or apply electrical signals at a corresponding location within the spinal cord. Because the attachment portion 110 and the implantation portion 120 have different implantation locations and methods, the required strength, adhesion, and flexibility of the attachment portion 110 and the implantation portion 120 may differ. Specifically, the attachment portion 110 and the implantation portion 120 may have different thicknesses and may be made of different materials. Alternatively, the attachment portion 110 and the implantation portion 120 may have the same thickness and be made of the same material. Furthermore, the flexible electrode may also include a rear end portion 130, which can be used to connect the flexible electrode 100 and rear end circuitry for a rear end connection, and an attachment portion 110 can extend from the rear end portion 130. The flexible electrode 100 has good flexibility, so when applied to the spinal cord, it can conform to the attachment or implantation site. Figure 1 The flexible electrode 100 shown includes an attachment portion 110 with an elongated shape, and ten implantation portions 120 symmetrically arranged along the two long sides of the attachment portion 110. However, it should be understood that... Figure 1 The examples shown are merely non-limiting; flexible electrodes for the spinal cord may have attachment portions 110 of different shapes and sizes and implant portions 120 of different numbers, shapes, sizes and arrangements, as needed.
[0022] Although Figure 1 The flexible electrode 100 shown includes both an attachment portion 110 and an implantation portion 120. However, it should be understood that the flexible electrode in this disclosure may also include only the attachment portion configured to be attached to the epidural space or the intradural space, without including the implantation portion configured to be implanted into the spinal cord or into the neural tissue connected to the spinal cord.
[0023] Figure 2 A schematic diagram illustrating at least a portion of the implantation of a flexible electrode 200 for the spinal cord according to an embodiment of the present disclosure is shown, particularly an enlarged view of the implanted electrode 200. Figure 2As shown, when the flexible electrode 200 is implanted into the spine, the attachment portion 210 can be parallel to the nerve bundles within the spine, and the implantation portion 220 can be perpendicular to the nerve bundles or at an angle relative to the vertical direction. Both the attachment portion 210 and each implantation portion 220 can include one or more electrode sites, which can be used to acquire electrical signals from or apply electrical signals to the spinal nerves. In this way, when the flexible electrode 200 is used as a recording electrode, the electrode sites of the attachment portion 210 can record local field potential (LFP) signals on the dura mater or the lateral portion of the white matter in contact with it, and the electrode sites of the implantation portion 220 can record spike signals of individual neurons in the spinal cord, nerve roots, and ganglia in contact with it, thus enabling the flexible electrode 200 to simultaneously record local field potential signals and spike signals; and when the flexible electrode 200 is used as a stimulation electrode, the electrode sites of the attachment portion 210 can apply electrical signals to the dura mater in contact with it, and the electrode sites of the implantation portion 220 can apply electrical signals to the spinal cord in contact with it. Figure 2 The illustration shows an embodiment of implanting a flexible electrode 200 into multiple spinal segments. However, it should be understood that this disclosure is not limited thereto. Rather, the size, shape, and arrangement of electrode sites of the flexible electrode can be adjusted as needed to make the flexible electrode suitable for one, multiple, or all spinal nerve segments when implanted into one, multiple, or all spinal segments, so as to achieve the function of recording electrophysiological signals and electrical stimulation of neurons in one, multiple, or all spinal cord segments.
[0024] Figure 3 An exploded view of at least a portion of a flexible electrode 300 according to an embodiment of the present disclosure is shown. Figure 3 It can be clearly seen that the flexible electrode 300 has a multi-layer structure, specifically including a bottom insulating layer 301, a top insulating layer 302, a conductive layer 303, an electrode site layer 304, a rear end site layer 306, and a flexible separation layer 308. It should be understood that... Figure 3 The layers of the flexible electrode 300 shown are merely non-limiting examples; the flexible electrode in this disclosure may omit one or more layers, and may include many other layers. The flexible electrode 300 may include a bottom insulating layer 301 and a top insulating layer 302. Specifically, as shown... Figure 3As shown, the attachment portion, implantation portion, and rear end portion of the flexible electrode 300 may all include insulating layers 301 and 302. The insulating layer in the flexible electrode can refer to the outer surface layer that serves an insulating function. Since the insulating layer of the flexible electrode needs to come into contact with biological tissue after implantation, the material of the insulating layer is required to have both good insulation and good biocompatibility. In embodiments of this disclosure, the materials of insulating layers 301 and 302 may include polyimide (PI), polydimethylsiloxane (PDMS), parylene, epoxy resin, polyamide-imide (PAI), SU-8 photoresist, silicone, silicone rubber, etc. In embodiments according to this disclosure, to further enhance the biodegradability of the flexible electrode, the materials of insulating layers 301 and 302 may also include polylactic acid, polylactic acid-glycolic acid copolymer, etc. Furthermore, insulating layers 301 and 302 are also the main components providing strength in the flexible electrode 300. An excessively thin insulating layer reduces the strength of the electrode, while an excessively thick insulating layer reduces its flexibility. Furthermore, implanting an electrode with an excessively thick insulating layer can cause significant damage to the organism. In embodiments according to this disclosure, the thickness of the insulating layers 301 and 302 can be from 100 nm to 300 μm, preferably from 300 nm to 20 μm.
[0025] The flexible electrode 300 may further include wires in a conductor layer 303 between a bottom insulating layer 301 and a top insulating layer 302. In embodiments according to this disclosure, the flexible electrode 300 may include one or more wires in the same conductor layer 303, wherein each wire may be electrically coupled to an electrode site in an electrode site layer 304 and electrically coupled to a rear end site in a rear end site layer 306. In embodiments of this disclosure, the thickness of the conductor layer 303 and each wire therein may be from 5 nm to 200 μm. The spacing between the wires may be as low as 10 nm, for example. The linewidth of the wires and the spacing between the wires may be from 10 nm to 500 μm, for example, preferably from 100 nm to 30 μm. It should be understood that the dimensions of the wires, etc., are not limited to the ranges listed above, but may vary according to design requirements.
[0026] In embodiments according to this disclosure, the conductors in the conductor layer 303 may be a thin film structure comprising multiple superimposed layers in the thickness direction. The materials of these layers may be materials that enhance the conductors' properties such as adhesion, ductility, and conductivity. As a non-limiting example, the conductor layer 303 may be a metal thin film comprising three superimposed layers, wherein the first and second layers, respectively in contact with the insulating layers 301 and 302, are adhesive layers and may be metallic or non-metallic adhesive materials such as titanium (Ti), titanium nitride (TiN), chromium (Cr), tantalum (Ta), or tantalum nitride (TaN); and the third layer, located between the first and second layers, is a conductive layer and may be a highly conductive material such as gold (Au), platinum (Pt), iridium (Ir), tungsten (W), platinum-iridium alloys, titanium alloys, graphite, carbon nanotubes, or PEDOT. In embodiments according to this disclosure, to further endow the flexible electrode with biodegradable properties, the conductive layer may also be made of materials such as magnesium (Mg), molybdenum (Mo), and their alloys. It should be understood that the conductive layer can be made of other conductive metallic or non-metallic materials, or it can be made of conductive polymer materials or composite conductive materials. In the embodiments according to this disclosure, the thickness of the adhesion layer can be from 1 nm to 50 nm, and the thickness of the conductive layer can be from 5 nm to 200 μm.
[0027] The flexible electrode 300 may further include electrode sites in a top electrode site layer 304 located above the top insulating layer 302, each electrode site being electrically coupled to one of the wires in the wire layer 303, and contacting the spinal cord after implantation of the flexible electrode 300 to acquire electrical signals from the spinal nerves and transmit the acquired electrical signals through the wires, or to apply the electrical signals received through the wires to the spinal nerves. Figure 3 In the flexible electrode 300 shown, each of the attachment portion and multiple implantation portions includes multiple corresponding electrode sites. However, it should be understood that this disclosure is not limited thereto; each implantation portion of the flexible electrode may include multiple electrode sites for applying or acquiring signals within the spinal cord, and the attachment portion of the flexible electrode may include multiple electrode sites for applying or acquiring signals on the surface of the spinal cord, as needed. Furthermore, since each electrode site is coupled to its corresponding wire, when the flexible electrode 300 is used as a stimulation electrode, each electrode site can synchronously or asynchronously apply the same or different electrical signals at different locations deep and / or on the surface; and when the flexible electrode 300 is used as a recording electrode, these electrode sites can simultaneously and precisely acquire electrical signals at different locations deep and / or on the surface.
[0028] In the flexible electrode 300, electrode sites in the top electrode site layer 304 can be electrically coupled to corresponding wires through vias in the top insulating layer 302 at positions corresponding to the electrode sites. When the flexible electrode includes multiple wires, it can correspondingly include multiple electrode sites in the top electrode site layer 304, and each of these electrode sites is electrically coupled to one of the multiple wires through a corresponding via in the top insulating layer 302. In embodiments according to this disclosure, the electrode sites in the top electrode site layer 304 can be a thin film structure comprising multiple superimposed layers in the thickness direction. The material of the adhesion layer adjacent to the wire layer 303 among the multiple layers can be a material that enhances the adhesion between the electrode sites and the wires, and the thickness of the adhesion layer can be from 1 nm to 50 nm. As a non-limiting example, the electrode site layer 304 can be a metal thin film comprising two superimposed layers, wherein the first layer adjacent to the wire layer 303 is Ti, TiN, Cr, Ta, or TaN, and the exposed second layer of the electrode site layer 304 is Au. It should be understood that the electrode site layer can also be similar to the conductive layer, made of other conductive metallic or non-metallic materials, such as Pt, Ir, W, Mg, Mo, platinum-iridium alloy, titanium alloy, graphite, carbon nanotubes, PEDOT, etc.
[0029] Each electrode site can have a planar size on the micrometer scale and a thickness on the nanometer scale. In embodiments according to this disclosure, the shape of the electrode sites can be configured as various regular or irregular shapes as needed, and the number can be one or more. The maximum side length or diameter of the electrode sites in the attachment portion can be 1 μm to 2 mm, and the spacing between the electrode sites can be 10 μm to 20 mm. The shape of the electrode sites in the implantation portion can be configured as various regular or irregular shapes as needed, with a maximum side length or diameter of 1 μm to 500 μm, and the spacing between the electrode sites can be 1 μm to 5 mm. It should be understood that the shape, number, size, and spacing of the electrode sites can be selected according to the characteristics of the biological tissue area to be recorded or stimulated.
[0030] In embodiments according to this disclosure, the exposed surface of the electrode site in contact with biological tissue may also have a surface-modified layer to improve the electrochemical properties of the electrode site. As a non-limiting example, the surface-modified layer can be obtained by methods such as electroinitiated polymerization coating of PEDOT:PSS, sputtering of iridium oxide films, etc., to reduce impedance (e.g., electrochemical impedance at an operating frequency of 1 kHz) when the flexible electrode acquires electrical signals, and to improve charge injection capability when the flexible electrode is stimulated by an electrical signal, thereby improving interaction efficiency.
[0031] In embodiments according to this disclosure, although in Figure 3Not shown, but the flexible electrode may further include electrode sites in a bottom electrode site layer 305 located below the bottom insulating layer 301, which can contact biological tissue after implantation to directly acquire or apply electrical signals. Similar to the electrode sites in the top electrode site layer 304, in the flexible electrode 300, the electrode sites in the bottom electrode site layer 305 can be electrically coupled to corresponding wires through through-holes in the bottom insulating layer 301 at positions corresponding to the electrode sites. In embodiments according to this disclosure, the electrode sites in the bottom electrode site layer 305 may be located at relative positions to the electrode sites in the top electrode site layer 304 on opposite sides of the top and bottom of the flexible electrode 300, and are electrically coupled to the same wire in the wire layer 303 to the electrode sites in the top electrode site layer 304 located at the opposite positions. In embodiments according to this disclosure, the electrode sites in the bottom electrode site layer 305 may also be located at different positions on the top and bottom sides of the flexible electrode 300, respectively, to collect or apply electrical signals in different regions of biological tissue; and in embodiments according to this disclosure, the electrode sites in the bottom electrode site layer 305 may also be electrically coupled to wires in the wire layer 303 that are different from the electrode sites in the top electrode site layer 304.
[0032] It should be understood that the bottom electrode site layer 305 is an optional, not essential, part of the flexible electrode. For example, the flexible electrode in this disclosure may include only the top electrode site layer 304 without the bottom electrode site layer 305. The shape, size, material, etc., of the bottom electrode sites may be similar to those of the top electrode sites, and will not be described in detail here.
[0033] In embodiments of this disclosure, the flexible electrode may further include additional conductive layers; that is, the flexible electrode in this disclosure may include one or more conductive layers. The dimensions, materials, manufacturing methods, etc., of the additional conductive layers may be similar to those of conductive layer 303, and will not be detailed here. When the flexible electrode includes additional conductive layers, these conductive layers may be spaced apart by additional insulating layers. The dimensions, materials, and manufacturing methods of the additional insulating layers may be similar to those of the bottom insulating layer 301 and / or the top insulating layer 302, and will not be detailed here. One or more conductors in these additional conductive layers may be electrically coupled to electrode sites located below the bottom insulating layer or above the top insulating layer through vias in one or more of the bottom insulating layer, the top insulating layer, and the additional insulating layers. By including multiple conductive layers in the flexible electrode, the number and accuracy of signals transmitted through the flexible electrode can be increased with the same cross-sectional width; that is, a high-precision and multi-channel electrode is provided, which is beneficial for achieving high-throughput interaction.
[0034] In embodiments according to this disclosure, the rear end portion of the flexible electrode 300 may include a rear end point in a rear end point layer 306. The rear end point can be electrically coupled to one of the wires and a rear end circuit via through-holes in the bottom insulating layer 301 and / or the top insulating layer 302 to achieve bidirectional signal transmission between the electrode point electrically coupled to the wire and the rear end circuit. Here, the rear end circuit can refer to circuitry located at the rear end of the flexible electrode, such as a signal recording circuit, signal processing circuit, signal generation circuit, etc., associated with a signal from the flexible electrode. Preferably, the rear end point layer 306 may be located between at least one of the top insulating layer 302 and the bottom insulating layer 301 and the wire layer 303. In embodiments according to this disclosure, the flexible electrode can be coupled to a back-end circuit via a connection. Specifically, the ball gate array (BGA) package site, serving as the back-end site, can be transferred to a commercial signal recording system via a printed circuit board (PCB), flexible printed circuit (FPC), etc. Before the transfer, the flexible electrode can be released from the substrate (e.g., by peeling the flexible electrode directly from the substrate, or by removing the flexible release layer to separate the flexible electrode from the substrate). The back-end portion is then connected to the back-end circuit using connection methods such as ball-mount patch and anisotropic conductive film bonding (ACF bonding), and then encapsulated using silicone or the like. In embodiments according to this disclosure, the flexible electrode can also be integrated with the back-end circuit; that is, the back-end portion of the flexible electrode is first connected to the back-end circuit, and then the entire electrode is separated from the substrate. Specifically, preprocessing functions such as signal amplification and filtering can be integrated onto a dedicated chip, and then connected and encapsulated to an integrated PCB at the back end of the flexible electrode via bonding or other methods, thereby enabling wireless transmission and charging. In this case, independent flexible electrodes and dedicated chips as back-end circuits can be used, and the electrical connection between the flexible electrodes and the dedicated chips can be achieved through methods such as ball-mount bonding or ACF bonding. Alternatively, a certain space can be reserved on the pre-fabricated wafer of the chip as the back-end circuit, and the electrodes can be fabricated directly on this basis. This enables the joint processing or separate processing of chips and electrodes, achieving a higher degree of integration.
[0035] The back-end sites can have micrometer-scale planar dimensions and nanometer-scale thicknesses. As a non-limiting example, the back-end sites can be BGA packaging sites with diameters ranging from 50 μm to 2000 μm, or they can be circular, elliptical, rectangular, rounded rectangular, or chamfered rectangular sites with side lengths ranging from 50 μm to 2000 μm. The thickness of the back-end site layer 306 and the back-end sites therein can range from 5 nm to 200 μm. It should be understood that the shape, size, etc., of the back-end sites are not limited to the ranges listed above, but can vary according to design requirements.
[0036] The back-end site for connection can include multiple layers in the thickness direction. The material of the adhesion layer near the conductor layer 303 can be a material that enhances the adhesion between the electrode site and the conductor. The material of the flux layer in the middle of the multiple layers can be a flux material. The conductive layer in the multiple layers can be other conductive metallic or non-metallic materials as described above for the conductor layer. The outermost layer that may be exposed through the insulating layers 301 and 302 is an oxidation-resistant protective layer. As a non-limiting example, the back-end site layer 306 can be a metal film comprising three superimposed layers. The first layer near the conductor layer 303 can be a nanoscale adhesion layer to improve the adhesion between the back-end site layer 306 and the conductor layer 303. The material of the first layer as the adhesion layer can be any one or a combination of chromium, tantalum, tantalum nitride, titanium, or titanium nitride. The material of the second layer as the flux layer can be nickel (Ni), Pt, or palladium (Pd). The material of the third layer as the conductive layer can be Au, Pt, Ir, W, Mg, Mo, platinum-iridium alloy, titanium alloy, graphite, carbon nanotubes, PEDOT, etc. It should be understood that the back-end site layer can also be made of other conductive metallic or non-metallic materials. Figure 3 The back-end site layer 306 serves as the part that connects to the back-end processing system or chip. The size, spacing, shape, etc. of its sites can be changed according to different connection methods of the back-end.
[0037] In embodiments according to this disclosure, the flexible electrode may not include site layers such as a top electrode site layer, a bottom electrode site layer, and a rear end site layer. In this case, the electrode sites on the electrode and the rear end sites for connection in the rear portion can both be portions of a wire layer and electrically coupled to corresponding wires in the wire layer. That is, the flexible electrode may not include a top electrode site layer, a bottom electrode site layer, and a rear end site layer, so both the electrode sites and the rear end sites are implemented in the wire layer. Furthermore, the electrode sites for sensing and applying electrical signals can directly contact the tissue region to which the electrode is implanted. As a non-limiting example, each electrode site can be electrically coupled to a corresponding wire in the wire layer and exposed to the outer surface of the electrode and in contact with biological tissue through corresponding vias in the top or bottom insulating layer. Similarly, in embodiments according to this disclosure, the rear end sites can also be connected to the rear-end circuit through corresponding vias in the top or bottom insulating layer, in which case the flexible electrode may not include a separate rear end site layer.
[0038] In embodiments according to this disclosure, the flexible electrode 300 may further include a flexible separation layer 308. Figure 3 The flexible separation layer 308 of the flexible electrode 300 is shown as being located at the bottom layer of the entire flexible electrode; however, it should be understood that the location of the flexible separation layer is not limited to this, and the flexible electrode may include one or more flexible separation layers located at different positions. Preferably, the flexible separation layer can be fabricated between the substrate and the bottom insulating layer. The flexible separation layer can be made of a material that can be removed by a specific substance (such as a solution) to separate the two portions of the flexible electrode above and below the flexible separation layer while avoiding damage to the flexible electrode. In embodiments of this disclosure, the material of the flexible separation layer can be a metallic or non-metallic material such as Ni, Cr, or aluminum (Al). It should be understood that the flexible separation layer is an optional but not necessary part of the flexible electrode, and without the flexible separation layer, the flexible electrode can be fabricated to be directly separable from the substrate. In embodiments according to this disclosure, the flexible separation layer 308 also includes an adhesive layer, the material of which can be chromium, tantalum, tantalum nitride, titanium, or titanium nitride.
[0039] Figure 4 A flowchart of a method 400 for manufacturing a flexible electrode according to an embodiment of the present disclosure is shown. In this disclosure, nanoscale flexible electrodes can be manufactured using fabrication methods based on Micro-Electro Mechanical System (MEMS) processes. Figure 4As shown, method 400 may include: at S41, fabricating a first insulating layer, a conductive layer, and a second insulating layer on a substrate, wherein a through-hole is fabricated by patterning at a position corresponding to an electrode site in at least one of the first and second insulating layers; and at S42, separating a flexible electrode from the substrate. The following is in conjunction with... Figures 5 to 7 The steps for fabricating each layer of the flexible electrode at S41 are described in detail.
[0040] Figure 5 A schematic diagram of a method 500 for manufacturing a flexible electrode according to an embodiment of the present disclosure is shown, wherein the attachment portion and the implantation portion of the flexible electrode have the same thickness and are made of the same material, and the flexible electrode includes at least a flexible separation layer, a bottom insulating layer, a conductive layer, a top insulating layer, and a top electrode site layer. Figure 5 The manufacturing process and structure of the flexible electrode, including the flexible separation layer, bottom insulating layer, conductive layer, top insulating layer, and electrode site layer, are described in more detail.
[0041] Figure 5 View (A) shows the substrate of the electrode. In embodiments according to this disclosure, a rigid substrate, such as glass, quartz, silicon wafer, etc., may be used. In embodiments of this disclosure, other soft materials may also be used as the substrate, such as the same material as the insulating layer.
[0042] Figure 5 View (B) illustrates the steps involved in fabricating a flexible separation layer on a substrate. The flexible separation layer can be removed by applying a specific substance, thereby facilitating the separation of the flexible portion of the electrode from the rigid substrate. Figure 5 The embodiments shown use Ni as the material for the flexible release layer, but other materials such as Cr and Al can also be used. In embodiments according to this disclosure, when fabricating the flexible release layer on a substrate by vapor deposition, a portion of the exposed substrate can be etched first, thereby improving the overall flatness of the substrate after vapor deposition. It should be understood that the flexible release layer is an optional, not necessary, component of the flexible electrode. Depending on the properties of the selected material, the flexible electrode can be easily separated even without a flexible release layer. In embodiments according to this disclosure, the flexible release layer may also have markings that can be used for alignment of subsequent layers.
[0043] Figure 5View (C) illustrates the fabrication of a bottom insulating layer on top of a flexible release layer. As a non-limiting example, when the insulating layer is made of polyimide, the fabrication of the bottom insulating layer may include steps such as film formation, film curing, and enhanced curing to create a thin film as the insulating layer. The film formation process may include coating polyimide onto the flexible release layer, for example, by spin-coating a layer of polyimide at segmented rotation speeds. Film curing may include gradually heating to a higher temperature and holding at that temperature to form a film for subsequent processing steps. Enhanced curing may include multi-gradient heating before fabricating subsequent layers, preferably in a vacuum or nitrogen atmosphere, followed by baking for several hours. It should be understood that the above-described fabrication process is merely a non-limiting example of the fabrication process for the bottom insulating layer, and one or more steps may be omitted, or more additional steps may be included.
[0044] It should be noted that the above manufacturing process pertains to an embodiment where a bottom insulating layer is fabricated in a flexible electrode without a bottom electrode site layer and where no vias correspond to the electrode sites are present in the bottom insulating layer. If the flexible electrode includes a bottom electrode site layer, the bottom electrode site layer can be fabricated on the flexible separation layer before fabricating the bottom insulating layer. For example, Au and Ti can be sequentially deposited on the flexible separation layer. The patterning step for the bottom electrode sites will be described in detail later regarding the top electrode sites. Accordingly, when the flexible electrode includes bottom electrode sites, the fabrication of the bottom insulating layer may include a patterning step, in addition to the steps described above, for etching vias at positions corresponding to the bottom electrode sites in the bottom insulating layer. The patterning step for the insulating layer will be described in detail later regarding the top insulating layer.
[0045] Figure 5 Views (D) to (G) illustrate the fabrication of a conductive layer on a bottom insulating layer. As shown in view (D), photoresist and a mask can be applied over the bottom insulating layer. It should be understood that other photolithographic methods, such as laser direct writing and electron beam lithography, can also be used for the fabrication of patterned thin films. In embodiments according to this disclosure, for metal thin films such as conductive layers, a double layer of photoresist can be applied to facilitate the fabrication (evaporation or sputtering) and stripping of the patterned thin film. By setting a pattern for the mask associated with the conductive layer, for example, it is possible to achieve... Figure 3The pattern of the conductive layer 303 shown is the outline of one or more conductors in the electrodes extending from the rear end portion. Next, exposure and development can be performed to obtain the structure shown in view (E). In embodiments according to this disclosure, exposure can be performed using contact lithography, exposing the mask and structure in a vacuum contact mode. In embodiments according to this disclosure, different developers and their concentrations can be used for patterns of different sizes. This step may also include layer-to-layer alignment. Next, film deposition can be performed on the structure shown in view (E), such as using processes like evaporation or sputtering, to deposit a thin metal film material, such as Au, to obtain the structure shown in view (F). Next, a stripping process can be performed to separate the film in the non-patterned areas from the film in the patterned areas by removing the photoresist in the non-patterned areas, to obtain the structure shown in view (G), i.e., the conductive layer is fabricated. In embodiments according to this disclosure, a second stripping process can be performed after the stripping to further remove residual photoresist from the structure surface.
[0046] In embodiments according to this disclosure, a back-end site layer may also be fabricated prior to the fabrication of the conductive layer. As a non-limiting example, the fabrication process of the back-end site layer may be similar to the fabrication process of the metal thin film described above with respect to the conductive layer.
[0047] Figure 5 Views (H) to (K) show the fabrication of the top insulating layer. For photosensitive films, patterning can generally be achieved directly through patterning exposure and development. However, for non-photosensitive materials used in the insulating layer, patterning cannot be achieved by exposing and developing the material itself. Therefore, a sufficiently thick patterned resist layer can be fabricated on top of this layer. Then, the film in the areas not covered by the resist layer is removed by dry etching (the resist layer will also become thinner, so it is necessary to ensure that the resist layer is thick enough). The resist layer is then removed to achieve the patterning of the non-photosensitive layer. As a non-limiting example, photoresist can be used as the resist layer in the fabrication of the insulating layer. The fabrication of the top insulating layer may include steps such as film deposition, film curing, patterning, and enhanced curing. View (H) shows the structure obtained after the top insulating layer is formed, View (I) shows the application of photoresist and a mask on the top insulating layer after film deposition, View (J) shows the structure including the resist layer obtained after exposure and development, and View (K) shows the structure including the fabricated top insulating layer. The film formation process, film curing, and enhanced curing have been detailed in the previous section on the bottom insulating layer and are omitted here for brevity. The patterning step can be performed after film curing or after enhanced curing; enhanced curing results in a more etch-resistant insulating layer. Specifically, in view (I), a sufficiently thick photoresist layer is fabricated on the insulating layer through steps such as spin coating and baking. By setting a mask pattern related to the top insulating layer, for example, [further details can be provided]. Figure 3The pattern of the top insulating layer 302 shown is the outline of the top insulating layer realized on one or more wires of the electrodes extending from the rear end portion, and the outline of the vias realized at positions corresponding to the electrode sites in the top insulating layer. In view (J), the pattern is transferred onto photoresist on the insulating layer through steps such as exposure and development to obtain an etch-resistant layer, wherein the portion to be removed from the top insulating layer is exposed. The exposed portion of the top insulating layer can be removed by oxygen plasma etching to obtain the structure shown in view (K).
[0048] In embodiments according to this disclosure, an adhesion-enhancing treatment may also be performed prior to the fabrication of the top insulating layer to improve the bonding strength between the bottom and top insulating layers.
[0049] Figure 5 The view (L) shows the fabrication of the top electrode site layer on top of the top insulating layer by methods such as vapor deposition.
[0050] Figure 6 A schematic diagram of a method 600 for manufacturing a flexible electrode according to an embodiment of the present disclosure is shown, wherein the attached portion and the implanted portion of the flexible electrode have different thicknesses, and the flexible electrode includes at least a flexible separation layer, a bottom insulating layer, a wire layer, a top insulating layer and a top electrode site layer.
[0051] Figure 6 Views (A) to (G) illustrating the fabrication of the flexible release layer, bottom insulation layer, and conductor layer are similar to those shown in the original. Figure 5 The views (A) to (G) are not described in detail here.
[0052] Figure 6 Views (H) to (K) show the fabrication of the top insulating layer. For simplicity, the fabrication process of the top insulating layer will not be described in detail here. Figure 5 Similar content to views (H) to (K). In order to make the attachment portion and the implant portion have different thicknesses, the top insulating layer of the attachment portion and the implant portion is made to have different thicknesses. Figure 6 View (H) shows the structure obtained after the top insulating layer is filmed. Figure 6 View (I) shows the application of photoresist and a mask over the top insulating layer after film deposition, wherein the pattern of the mask is set in relation to the top insulating layer, for example, to achieve... Figure 3 The pattern of the top insulating layer 302 shown is the outline of the top insulating layer implemented on one or more wires of the electrodes extending from the rear end portion, and the outline of the through-holes implemented at positions corresponding to the electrode sites in the top insulating layer. Figure 6 View (J) shows the structure including the etch-resistant layer obtained after exposure and development. Figure 6View (K) shows the structure of the top insulating layer after etching, where the thickness of the top insulating layer is the same for both the attached portion and the implanted portion. Figure 6 View (L) shows the application of photoresist and a mask again on the top insulating layer after etching in view (K), wherein the pattern of the mask is set to relate to the top insulating layer of the attachment portion, for example, enabling the following: Figure 3 The pattern of the top insulating layer 302 of the attached portion shown. Figure 6 View (M) shows the structure including an anti-etching layer obtained after re-exposure and development, which is located on the insulating layer of the attachment portion to protect the insulating layer of the attachment portion and expose the insulating layer of the implanted portion. Figure 6 View (N) shows the final top insulating layer obtained after etching, where a portion of the insulating layer of the implanted portion was etched away, so its thickness is less than that of the insulating layer of the attached portion.
[0053] Figure 6 View (O) shows the fabrication of the top electrode site layer on top of the top insulating layer by methods such as vapor deposition.
[0054] Figure 7 A schematic diagram of a method 700 for manufacturing a flexible electrode according to an embodiment of the present disclosure is shown, wherein the attached portion and the implanted portion of the flexible electrode have different thicknesses, and the flexible electrode includes at least a flexible separation layer, a bottom insulating layer, a wire layer and a top insulating layer, but does not include an electrode site layer.
[0055] Figure 7 Views (A) to (N) are similar Figure 6 Views (A) to (N), but it should be noted that, unlike... Figure 5 and Figure 6 The mask in view (D) has a pattern associated with the wires, electrode sites, and back-end sites, such that the resulting flexible electrode's wire layer includes the flexible electrode's wires, electrode sites for acquiring or applying electrical signals, and back-end sites for connecting to back-end circuitry. Furthermore, unlike... Figure 5 and Figure 6 , Figure 7 The method shown does not include the step of fabricating the top electrode site layer.
[0056] This invention provides a flexible electrode for the spinal cord and its manufacturing method. The electrode possesses both deep and surface structures, allowing it to be attached to the epidural space or implanted within the spinal cord. It can be used for spinal cord electrical signal acquisition, simultaneously recording epidural and spinal cord LFP and Spike signals, and for functional electrical stimulation of the spinal cord both intraspinally and epidurally. By proportionally increasing or decreasing the electrode size, it can be adapted to different humans or other vertebrates. Electrodes with different numbers of layers, sizes, shapes, electrode sites, and arrangements can be designed and manufactured using nanotechnology. This electrode exhibits excellent spatial resolution and a high channel count, enabling the recording of a large number of neuronal activities, thus facilitating further motor decoding and fine motor manipulation. The material used in this flexible electrode significantly reduces electrode stiffness, effectively preventing breakage and providing a long-term stable spinal nerve interface when applied to the repeatedly deforming spinal cord. The material used in this flexible electrode induces only a mild immune response after implantation, and its ultra-thin structure prevents microenvironment deterioration and surrounding neuronal death, further improving its biocompatibility and chronic stability.
[0057] This flexible electrode has promising application prospects and value in neuroscience research and rehabilitation medicine.
[0058] The terms “front,” “back,” “top,” “bottom,” “above,” “below,” etc., used in the specification and claims, if present, are for descriptive purposes and are not necessarily used to describe unchanging relative positions. It should be understood that such terms are interchangeable where appropriate, so that embodiments of this disclosure described herein can, for example, operate on orientations different from those shown or otherwise described herein.
[0059] As used herein, the term "exemplary" means "serving as an example, instance, or illustration," and not as a "model" to be precisely copied. Any implementation described herein by example is not necessarily to be construed as preferred or advantageous over other implementations. Furthermore, this disclosure is not limited to any theory expressed or implied as given in the foregoing technical field, background, summary of invention, or detailed description.
[0060] As used herein, the term "substantially" means any minor variation resulting from design or manufacturing defects, device or component tolerances, environmental influences, and / or other factors. The term "substantially" also allows for differences from the perfect or ideal situation due to parasitic effects, noise, and other practical considerations that may exist in the actual implementation.
[0061] For reference purposes only, terms such as “first,” “second,” and similar terms may be used in this document and are therefore not intended to be limiting. For example, unless the context clearly indicates otherwise, the words “first,” “second,” and other such numerical terms relating to structures or elements do not imply order or sequence.
[0062] It should also be understood that when the term “including / contains” is used herein, it indicates the presence of the indicated feature, whole, step, operation, unit and / or component, but does not preclude the presence or addition of one or more other features, wholes, steps, operations, units and / or components and / or combinations thereof.
[0063] As used herein, the term “and / or” includes any and all combinations of one or more of the listed items in association. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of this disclosure. As used herein, the singular forms “a,” “an,” and “the” are also intended to include the plural forms unless the context clearly indicates otherwise.
[0064] Those skilled in the art will recognize that the boundaries between the above operations are merely illustrative. Multiple operations may be combined into a single operation, a single operation may be distributed among additional operations, and operations may be performed with at least partial overlap in time. Moreover, alternative embodiments may include multiple instances of a particular operation, and the order of operations may be changed in various other embodiments. However, other modifications, variations, and substitutions are equally possible. Therefore, this specification and the accompanying drawings should be considered illustrative rather than restrictive.
[0065] While specific embodiments of this disclosure have been described in detail by way of example, those skilled in the art should understand that the examples are for illustrative purposes only and not intended to limit the scope of this disclosure. The various embodiments disclosed herein can be combined in any way without departing from the spirit and scope of this disclosure. Those skilled in the art should also understand that various modifications can be made to the embodiments without departing from the scope and spirit of this disclosure. The scope of this disclosure is defined by the appended claims.
Claims
1. A flexible electrode for a spinal cord, the flexible electrode comprising an attaching portion configured to be attachable outside the white matter of the epidural space or the intradural space and configured to collect or apply an electrical signal at the surface of the spinal cord, wherein the attaching portion of the flexible electrode comprising a first insulating layer and a second insulating layer and a wire layer between the first insulating layer and the second insulating layer, wherein the attaching portion of the flexible electrode further comprises one or more electrode sites, each electrode site being electrically coupled to one of the wires in the wire layer and being in contact with the spinal cord after implantation of the flexible electrode to collect an electrical signal from the spinal nerve and transmit the collected electrical signal through the wire, or to apply an electrical signal received through the wire to the spinal nerve, wherein the flexible electrode further comprises one or more implanting portions, each implanting portion extending from the attaching portion and being configured to be implantable into the spinal cord or into a nerve tissue connected with the spinal cord and being configured to collect or apply an electrical signal at a corresponding position inside the spinal cord, wherein the implanting portion comprises a first insulating layer and a second insulating layer and a wire layer between the first insulating layer and the second insulating layer, wherein the implanting portion further comprises one or more electrode sites, each electrode site being electrically coupled to one of the wires in the wire layer and being in contact with the spinal cord after implantation of the flexible electrode to collect an electrical signal from the spinal nerve and transmit the collected electrical signal through the wire, or to apply an electrical signal received through the wire to the spinal nerve, and wherein the attaching portion and the implanting portion of the flexible electrode have the same or different thicknesses and are made of the same or different materials.
2. The flexible electrode of claim 1, wherein: the flexible electrode comprises a plurality of wire layers, the plurality of wire layers being spaced apart by additional insulating layers, and each wire layer comprising a plurality of wires spaced apart from each other.
3. The flexible electrode of claim 1, wherein: the electrode sites are in electrode site layers outside at least one of the first insulating layer and the second insulating layer and are electrically coupled to the wires in the wire layer through vias in the at least one layer.
4. The flexible electrode of claim 3, wherein, the electrode sites comprise a conductive sublayer, the conductive sublayer being made of any one of gold, platinum, iridium, tungsten, magnesium, molybdenum, platinum-iridium alloy, titanium alloy, graphite, carbon nanotube, PEDOT, or a combination thereof.
5. The flexible electrode of claim 4, wherein, the electrode sites further comprise an adhesive sublayer close to the wire layer, the adhesive sublayer being made of a material capable of enhancing adhesion of the electrode sites to the wire layer.
6. The flexible electrode of claim 2, wherein: the electrode sites are in the wire layer and are exposed through vias in at least one of the first insulating layer and the second insulating layer.
7. The flexible electrode of claim 1, wherein, the electrode sites are shaped as needed and are one or more in number, wherein: the maximum side length or diameter of the electrode sites of the attaching portion is 1 micrometer to 2 millimeters, and the spacing between the electrode sites is 10 micrometers to 20 millimeters; the maximum side length or diameter of the electrode sites of the implanting portion is 1 micrometer to 500 micrometers, and the spacing between the electrode sites is 1 micrometer to 5 millimeters.
8. The flexible electrode of claim 1, further comprising a back end portion, wherein: the attachment portion extends from the back end portion, and the back end portion includes a back end site coupled to one of the conductive lines in the conductive line layer and the back end circuitry to enable bidirectional signal transmission between the electrode site electrically coupled to the one of the conductive lines and the back end circuitry.
9. The flexible electrode of claim 8, wherein, is separated from the base of the flexible electrode after coupling the back end portion to the back end circuitry, or is coupled to the back end circuitry after the flexible electrode is separated from the base.
10. The flexible electrode of claim 8, wherein: the back end site is located in the conductive line layer and is interfaced to the back end circuitry through a via in at least one of the first and second insulating layers; or the back end site is located in a back end site layer between at least one of the first and second insulating layers and the conductive line layer, and is electrically coupled to the conductive line in the conductive line layer through a via in the at least one layer.
11. The flexible electrode of claim 8, wherein, the back end site includes a conductive sublayer, a material of the conductive sublayer being any one or a combination of gold, platinum, iridium, tungsten, magnesium, molybdenum, platinum-iridium alloy, titanium alloy, graphite, carbon nanotube, PEDOT.
12. The flexible electrode of claim 8, wherein, a thickness of the back end site is 5 nanometers to 200 micrometers.
13. The flexible electrode of claim 11, wherein, the back end site further includes an adhesion sublayer proximate to the conductive line layer, a material of the adhesion sublayer being any one or a combination of chromium, tantalum, tantalum nitride, titanium, or titanium nitride.
14. The flexible electrode of claim 1, wherein, the conductive line layer includes a conductive sublayer, a material of the conductive sublayer being any one or a combination of gold, platinum, iridium, tungsten, platinum-iridium alloy, titanium alloy, graphite, carbon nanotube, PEDOT.
15. The flexible electrode of claim 14, wherein, a thickness of the conductive sublayer is 5 nanometers to 200 micrometers.
16. The flexible electrode of claim 8, wherein, the conductive line layer includes a conductive sublayer and an adhesion sublayer proximate to any one of the electrode site and the back end site, a material of the adhesion sublayer being any one or a combination of chromium, tantalum, tantalum nitride, titanium, or titanium nitride.
17. The flexible electrode of claim 1, wherein, a thickness of the first and second insulating layers is 100 nanometers to 300 micrometers.
18. The flexible electrode of claim 1, wherein, a material of the first and second insulating layers is any one or a combination of polyimide, polydimethylsiloxane, parylene, epoxy, polyamide-imide, SU-8 photoresist, silicone gel, silicone rubber.
19. The flexible electrode of claim 1, further comprising a flexible separation layer, wherein, the flexible separation layer is removable by a specific substance to separate a portion of the flexible electrode and avoid damage to the flexible electrode.
20. The flexible electrode of claim 19, wherein, a material of the flexible separation layer is any one or a combination of nickel, chromium, aluminum.
21. The flexible electrode of claim 19, wherein, the flexible separation layer further includes an adhesion sublayer, a material of the adhesion sublayer being chromium, tantalum, tantalum nitride, titanium, or titanium nitride.
22. The flexible electrode of claim 1, wherein, the attachment portion is parallel to a nerve bundle within the spinal column, and the implant portion is perpendicular or at an angle relative to perpendicular to the nerve bundle.
23. The flexible electrode of claim 1, wherein: the electrode site of the attachment portion is configured to enable recording of local field potential signals epidurally or intradurally outside the lateral white matter, and the electrode site of the implant portion is configured to enable recording of spike potential signals of individual neurons within the nerve root, ganglion, and inside the spinal cord to enable simultaneous recording of local field potential signals and spike potential signals using the flexible electrode; and and The electrode sites of the attaching portion are configured to be capable of applying electrical signals at the lateral white matter outside the dura mater or the endura, and the electrode sites of the implanting portion are configured to be capable of applying electrical signals at the nerve root, the ganglion, and the internal part of the spinal cord.
24. The flexible electrode of claim 1, wherein, The flexible electrode comprises an elongated attaching portion and a plurality of implanting portions extending from opposite two long edges of the attaching portion.
25. The flexible electrode of claim 24, wherein, The plurality of implanting portions are symmetrically or asymmetrically arranged on the two long edges.
26. The flexible electrode of claim 1, wherein, The material of the wire layer is any one or a combination of magnesium, molybdenum and alloys thereof, and the material of the first and second insulating layers is any one or a combination of polylactic acid and poly(lactic-co-glycolic acid) so that the flexible electrode is biodegradable.
27. The flexible electrode of claim 1, wherein, The flexible electrode is configured to be capable of being used for one spinal segment, multiple spinal segments, or all spinal segments, thereby collecting or applying electrical signals to neurons in one spinal segment, multiple spinal segments, or all spinal segments, respectively.
28. A manufacturing method of a flexible electrode for a spinal cord, the flexible electrode being the flexible electrode of any one of claims 1-27, the method comprising: manufacturing a first insulating layer, a wire layer, a second insulating layer, and electrode sites on a substrate; and separating the flexible electrode from the substrate; wherein a via is manufactured by patterning at a position of at least one of the first and second insulating layers corresponding to the electrode sites.
29. The manufacturing method of claim 28, wherein: the electrode sites are manufactured to be in the wire layer and exposed through the via in at least one of the first and second insulating layers; or the electrode sites are manufactured to be in an electrode site layer outside at least one of the first and second insulating layers and electrically coupled to the wires in the wire layer through the via in the at least one layer.
30. The manufacturing method of claim 28, wherein: the back end sites are manufactured to be in the wire layer and interfaced to the back end circuitry through the via in at least one of the first and second insulating layers; or the back end sites are manufactured to be in a back end site layer between at least one of the first and second insulating layers and the wire layer and electrically coupled to the wires in the wire layer through the via in the at least one layer.
Citation Information
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