WO2023240695A1 - 一种用于脊髓的柔性电极及其制造方法 - Google Patents

一种用于脊髓的柔性电极及其制造方法 Download PDF

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Publication number
WO2023240695A1
WO2023240695A1 PCT/CN2022/102350 CN2022102350W WO2023240695A1 WO 2023240695 A1 WO2023240695 A1 WO 2023240695A1 CN 2022102350 W CN2022102350 W CN 2022102350W WO 2023240695 A1 WO2023240695 A1 WO 2023240695A1
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layer
electrode
flexible electrode
insulating layer
flexible
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PCT/CN2022/102350
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English (en)
French (fr)
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李雪
赵郑拓
李肖城
樊杰
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中国科学院脑科学与智能技术卓越创新中心
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Publication of WO2023240695A1 publication Critical patent/WO2023240695A1/zh

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
    • A61B5/25—Bioelectric electrodes therefor
    • A61B5/263—Bioelectric electrodes therefor characterised by the electrode materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
    • A61B5/25—Bioelectric electrodes therefor
    • A61B5/279—Bioelectric electrodes therefor specially adapted for particular uses
    • A61B5/294—Bioelectric electrodes therefor specially adapted for particular uses for nerve conduction study [NCS]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
    • A61B5/316—Modalities, i.e. specific diagnostic methods
    • A61B5/388—Nerve conduction study, e.g. detecting action potential of peripheral nerves
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6846—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive
    • A61B5/6867—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive specially adapted to be attached or implanted in a specific body part
    • A61B5/6877—Nerve
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6846—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive
    • A61B5/6867—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive specially adapted to be attached or implanted in a specific body part
    • A61B5/6878—Bone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode
    • A61N1/0551—Spinal or peripheral nerve electrodes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/3606—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
    • A61N1/36062—Spinal stimulation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/372—Arrangements in connection with the implantation of stimulators
    • A61N1/375—Constructional arrangements, e.g. casings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
    • A61B2562/02—Details of sensors specially adapted for in-vivo measurements
    • A61B2562/0209—Special features of electrodes classified in A61B5/24, A61B5/25, A61B5/283, A61B5/291, A61B5/296, A61B5/053
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
    • A61B2562/12—Manufacturing methods specially adapted for producing sensors for in-vivo measurements
    • A61B2562/125—Manufacturing methods specially adapted for producing sensors for in-vivo measurements characterised by the manufacture of electrodes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
    • A61B2562/16—Details of sensor housings or probes; Details of structural supports for sensors
    • A61B2562/164—Details of sensor housings or probes; Details of structural supports for sensors the sensor is mounted in or on a conformable substrate or carrier

Definitions

  • the present disclosure relates to the technical field of life sciences, and more specifically to a flexible electrode for spinal cord and a manufacturing method thereof.
  • Spinal nerve electrodes include epidural electrodes and intraspinal electrodes.
  • a flexible electrode for a spinal cord comprising: an attachment portion configured to be external to the white matter epidurally or intradurally, and is configured to collect or apply electrical signals on the surface of the spinal cord; wherein the attached portion of the flexible electrode includes a first insulating layer and a second insulating layer and a wire layer located between the first insulating layer and the second insulating layer; Wherein, the attached part of the flexible electrode also includes one or more electrode sites, each electrode site is electrically coupled to one of the wires in the wire layer, and is in contact with the spinal cord after the flexible electrode is implanted to from The spinal nerves collect electrical signals and transmit the collected electrical signals through the wires, or apply the electrical signals received through the wires to the spinal nerves.
  • a method of manufacturing a flexible electrode for spinal cord comprising: manufacturing on a substrate The first insulating layer, the conductor layer, the second insulating layer and the electrode sites; and separating the flexible electrode from the substrate; wherein, by patterning at least one layer of the first insulating layer and the second insulating layer with the electrode sites Through holes are made at corresponding locations.
  • FIG. 1 shows a schematic diagram of at least a portion of a flexible electrode for the spinal cord according to an embodiment of the present disclosure
  • FIG. 2 shows a schematic diagram of an implantation manner of at least a portion of a flexible electrode for the spinal cord according to an embodiment of the present disclosure
  • FIG. 3 shows an exploded view of at least a portion of a flexible electrode in accordance with an embodiment of the present disclosure
  • FIG. 4 shows a flow chart of a method of manufacturing a flexible electrode according to an embodiment of the present disclosure
  • FIG. 5 shows a schematic diagram of a method of manufacturing a flexible electrode according to an embodiment of the present disclosure
  • FIG. 6 shows a schematic diagram of a method of manufacturing a flexible electrode according to an embodiment of the present disclosure
  • FIG. 7 shows a schematic diagram of a method of manufacturing a flexible electrode according to an embodiment of the present disclosure.
  • any specific values are to be construed as illustrative only and not as limiting. Accordingly, other examples of the exemplary embodiments may have different values.
  • LFP local field potential
  • Intraspinal electrodes can record LFP simultaneously by utilizing higher spatial accuracy. and single neuron spike signals; however, current intraspinal electrodes also face various challenges. Electrodes with a lower channel number are limited by the number of recorded neuronal activities and cannot fully utilize their spatial resolution for motion decoding.
  • the physical fragility caused by the stiffness of the electrode material may cause the electrode to break during the electrical interface and real-time decoding and result in the inability to record stably for a long time; for stimulation Generally speaking, the stimulation accuracy is low, and it can only stimulate the nerve bundles, which are far away from the motor nerves.
  • FIG. 1 shows a schematic diagram of at least a portion of a flexible electrode 100 for the spinal cord, in accordance with an embodiment of the present disclosure.
  • the flexible electrode 100 may include an attachment portion 110 that may be configured to be external to the white matter epidurally or intradurally and configured to collect or apply electrical signals at the surface of the spinal cord.
  • the flexible electrode 100 may also include one or more implant portions 120 that are symmetrically or asymmetrically arranged, each extending from the attachment portion, and may be configured to be implantable within the spinal cord or with the spinal cord.
  • the spinal cord connects the interior of neural tissue (such as nerve roots, ganglia, etc.) and is configured to collect or apply electrical signals at corresponding locations within the spinal cord.
  • neural tissue such as nerve roots, ganglia, etc.
  • the attachment part 110 and the implant part 120 have different implantation locations and implantation methods, the strength, adhesion, ductility, etc. required to be achieved by the attachment part 110 and the implant part 120 may be different.
  • the attachment part 110 and the implant part 120 may have different thicknesses and may also be made of different materials.
  • the attachment part 110 and the implant part 120 may also have the same thickness and be made of the same material.
  • the flexible electrode may further include a rear end portion 130 that can be used to couple the flexible electrode 100 and the rear end circuit to perform a rear end transfer, and the 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 location where it is attached or implanted.
  • the flexible electrode 100 shown in FIG. 1 includes an attachment portion 110 having an elongated shape, and 10 implant portions 120 symmetrically arranged on two long sides of the attachment portion 110 .
  • the flexible electrode for the spinal cord can have different shapes and sizes of attachment portions 110 and different numbers, shapes, sizes and arrangements of implant portions as needed. 120.
  • the flexible electrode 100 shown in FIG. 1 includes both an attachment portion 110 and an implant portion 120, it should be understood that the flexible electrode in the present disclosure may also include only one configured to be attached to the epidural or epidural membrane.
  • the intradural attachment portion does not include an implant portion configured to be implanted into the spinal cord or into neural tissue connected to the spinal cord.
  • FIG. 2 shows a schematic diagram of an implantation manner of at least a portion of a flexible electrode 200 for the spinal cord according to an embodiment of the present disclosure, particularly an enlarged view of the electrode 200 after implantation.
  • the attachment portion 210 can be parallel to the nerve bundle in the spine, and the implant portion 220 can be perpendicular to the nerve bundle or at an angle relative to the vertical direction.
  • the attachment portion 210 and each implant portion 220 may include one or more electrode sites that may be used to collect electrical signals from or apply electrical signals to spinal nerves.
  • the electrode site of the attached portion 210 can record a local field potential (LFP) signal on the dura mater or the outer part of the white matter in contact with it.
  • the electrode sites of the entry part 220 can record the spike signals of each neuron in the spinal nerves, nerve roots and ganglia in contact with them, so that the flexible electrode 200 can be used to simultaneously record local field potential signals and spike signals; and
  • the electrode sites of the attached part 210 can apply electrical signals to the dura mater in contact with it, and the electrode sites of the implanted part 220 can apply electrical signals to the spinal cord in contact with it.
  • FIG. 2 shows an embodiment in which flexible electrodes 200 are implanted into multiple spinal segments, but it should be understood that the present disclosure is not limited thereto, and the size, shape, and electrode sites of the flexible electrodes can be adjusted as needed. Arrangements, etc., so that the flexible electrode is suitable for one, multiple or all spinal nerves when implanted into one spinal segment, multiple spinal segments or all spinal segments, so as to realize the control of a segment of spinal cord, multiple segments of spinal cord or all spinal cords. Electrophysiological signal recording and electrical stimulation functions of neurons.
  • Figure 3 shows an exploded view of at least a portion of flexible electrode 300 in accordance with an embodiment of the present disclosure.
  • the flexible electrode 300 has a multi-layer structure, specifically, including a bottom insulation layer 301, a top insulation layer 302, a wire layer 303, an electrode site layer 304, a back-end site layer 306, a flexible Separation layer 308, etc.
  • the layers of the flexible electrode 300 shown in FIG. 3 are only non-limiting examples, and the flexible electrode in the present disclosure may omit one or more of the layers, and may also include more other layers.
  • the flexible electrode 300 may include an insulating layer 301 at the bottom and an insulating layer 302 at the top. Specifically, as shown in FIG.
  • the attachment part, the implanted part and the rear end part of the flexible electrode 300 may all include the insulating layer 301 ,302.
  • the insulation layer in the flexible electrode may refer to the outer surface layer of the electrode that plays an insulating role. Since the insulating layer of the flexible electrode needs to be in contact with biological tissue after implantation, the material of the insulating layer is required to have good insulation and good biocompatibility.
  • the materials of the insulating layers 301 and 302 may include polyimide (PI), polydimethylsiloxane (PDMS), parylene (Parylene), epoxy resin, Polyamide-imide (PAI), SU-8 photoresist, silicone, silicone rubber, etc.
  • the materials of the insulating layers 301 and 302 may also include polylactic acid, polylactic acid-glycolic acid copolymer, etc.
  • the insulating layers 301, 302 are also the main part of the flexible electrode 300 that provide strength. An insulating layer that is too thin will reduce the strength of the electrode, and an insulating layer that is too thick will reduce the flexibility of the electrode. Moreover, the implantation of an electrode including an insulating layer that is too thick will cause greater damage to the living body.
  • the thickness of the insulating layers 301, 302 may be 100 nm to 300 ⁇ m, preferably 300 nm to 20 ⁇ m.
  • the flexible electrode 300 may also include wires in the wire layer 303 between the bottom insulating layer 301 and the top insulating layer 302 .
  • flexible electrode 300 may include one or more conductors in the same conductor layer 303 , wherein each conductor may be electrically coupled to an electrode site in electrode site layer 304 and to a rear Backend sites in endsite layer 306.
  • the thickness of the wire layer 303 and each wire therein may range from 5 nm to 200 ⁇ m.
  • the spacing between the individual conductors can be as low as 10 nm, for example.
  • the line width of the conductive lines and the spacing between each conductive line may be, for example, 10 nm to 500 ⁇ m, for example, preferably 100 nm to 30 ⁇ m. It should be understood that the size of the wires, etc. are not limited to the ranges listed above, but can vary according to design needs.
  • the wires in the wire layer 303 may be a thin film structure including a plurality of superimposed layers in the thickness direction. These layered materials may be materials that enhance the conductor's properties such as adhesion, extensibility, conductivity, etc.
  • the conductive layer 303 may be a metal film including three stacked layers, wherein the first layer and the second layer in contact with the insulating layers 301 and 302 respectively are adhesive layers, which may be Titanium (Ti), titanium nitride (TiN) chromium (Cr), tantalum (Ta) or tantalum nitride (TaN) and other metal adhesive materials or non-metal adhesive materials are located in the first layer and the second layer
  • the third layer between the layers is the conductive layer, which can be gold (Au), platinum (Pt), iridium (Ir), tungsten (W), platinum-iridium alloy, titanium alloy, graphite, carbon nanotube, PEDOT Materials with good electrical conductivity.
  • the conductive layer may also be made of materials such as magnesium (Mg), molybdenum (Mo) and their alloys. It should be understood that the conductor layer can be made of other conductive metal materials or non-metallic materials, or can also be made of polymer conductive materials and composite conductive materials.
  • the thickness of the adhesive layer may be 1 nm to 50 nm, and the thickness of the conductive layer may be 5 nm to 200 ⁇ m.
  • the flexible electrode 300 may also 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 conductors in the conductor layer 303 and implanted on the flexible electrode 300. After entering, it makes contact with the spinal cord to collect electrical signals from the spinal nerves and transmit the collected electrical signals through the wires, or to apply the electrical signals received through the wires to the spinal nerves.
  • the attachment portion and each of the plurality of implant portions include a plurality of corresponding electrode sites.
  • the present disclosure is not limited thereto.
  • Each implanted portion of the flexible electrode may include multiple electrode sites for applying or collecting signals inside the spinal cord as needed, and the attached portion of the flexible electrode may include Multiple electrode sites used to apply or collect signals on the surface of the spinal cord. Additionally, since each electrode site is coupled to its corresponding lead, when flexible electrode 300 is used as a stimulating electrode, each of the electrode sites can apply the same force at different locations deep and/or superficially, either synchronously or asynchronously. or different electrical signals; and when the flexible electrode 300 is used as a recording electrode, these electrode sites can simultaneously and precisely collect electrical signals at different locations in the depth and/or surface.
  • an electrode site in the top electrode site layer 304 can be electrically coupled to a corresponding wire through a via hole in the top insulating layer 302 at a position corresponding to the electrode site.
  • the flexible electrode may accordingly include a plurality of electrode sites in the top electrode site layer 304, and each of the electrode sites may be connected to a plurality of electrode sites through corresponding through holes in the top insulating layer 302.
  • One of the conductors is electrically coupled.
  • the electrode sites in the top electrode site layer 304 may be a thin film structure including a plurality of stacked layers in the thickness direction.
  • the material of the adhesion layer close to the wire layer 303 in the multiple layers may be a material that can enhance the adhesion between the electrode site and the wire, and the thickness of the adhesion layer may be 1 nm to 50 nm.
  • the electrode site layer 304 may be a metal film including two superimposed layers, wherein the first layer close to the wire layer 303 is Ti, TiN, Cr, Ta or TaN, and the electrode site layer The exposed second layer of 304 is Au.
  • the electrode site layer can also be made of other conductive metallic materials or non-metallic materials, such as Pt, Ir, W, Mg, Mo, platinum-iridium alloy, titanium alloy, and graphite, similar to the wire layer. , carbon nanotubes, PEDOT, etc.
  • Each electrode site may have planar dimensions on the micron scale and thickness on the nanoscale.
  • the shape of the electrode site can be set into 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 of the attached part can be 1 ⁇ m to 2 mm, and the spacing between the electrode sites can be 10 ⁇ m to 20 mm.
  • the shape of the electrode sites of the implanted part can be set into various regular or irregular shapes as needed, the maximum side length or diameter can be 1 ⁇ m to 500 ⁇ m, and the spacing between electrode sites can be 1 ⁇ m to 5 mm. It should be understood that the shape, number, size, spacing, etc. of the electrode sites can be selected according to the conditions of the biological tissue area to be recorded or stimulated.
  • the surface of the electrode site that is exposed in contact with the biological tissue may also have a surface modification layer to improve the electrochemical characteristics of the electrode site.
  • the surface modification layer can be obtained by electrically initiated polymerization coatings using PEDOT:PSS, sputtering iridium oxide films, etc., for reducing impedance in the case of flexible electrodes collecting electrical signals (such as 1kHz operation electrochemical impedance at frequency), as well as improved charge injection capabilities under electrical signal stimulation applied by flexible electrodes, thereby improving interaction efficiency.
  • the flexible electrode may also include electrode sites in the bottom electrode site layer 305 below the bottom insulating layer 301 , after the flexible electrode is implanted.
  • the electrode site can be in contact with biological tissue to directly collect or apply electrical signals.
  • the electrode sites in the bottom electrode site layer 305 can pass through the electrode sites in the bottom insulating layer 301 at positions corresponding to the electrode sites.
  • the vias are electrically coupled to corresponding conductors.
  • the electrode sites in the bottom electrode site layer 305 may be located at opposite positions to the electrode sites in the top electrode site layer 304 on both top and bottom sides of the flexible electrode 300 and with Electrode sites in the oppositely located top electrode site layer 304 are electrically coupled to the same conductors in the conductor layer 303 .
  • 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 than the electrode sites in the top electrode site layer 304, so as to Electrical signals are collected or applied in different areas of biological tissue; and in embodiments according to the present disclosure, the electrode sites in the bottom electrode site layer 305 can also be electrically coupled to the top electrode site layer 304 in the wire layer 303 The electrode sites in the wires are different.
  • the bottom electrode site layer 305 is an optional but not essential part of the flexible electrode.
  • the flexible electrode in the present disclosure may only include the top electrode site layer 304 but not the bottom electrode site layer 305 .
  • the shape, size, material, etc. of the bottom electrode site may be similar to the top electrode site and will not be described in detail here.
  • the flexible electrode may also include additional wire layers, that is, the flexible electrode in the present disclosure may include one or more wire layers.
  • the size, material, manufacturing method, etc. of the additional conductor layer may be similar to the conductor layer 303 and will not be described in detail here.
  • these conductive layers may be separated by additional insulating layers, which may be similar in size, material, and manufacturing method to the bottom insulating layer 301 and/or the top insulating layer 302, where No more details.
  • One or more of the additional conductive layers may be electrically coupled to the bottom insulating layer or to the top insulating layer through vias in one or more of the bottom insulating layer, the top insulating layer, the additional insulating layers. electrode sites on.
  • the back end portion of the flexible electrode 300 may include a back end site in the back end site layer 306 , and the back end site may be passed through the bottom insulating layer 301 and/or the top insulating layer 302 .
  • the via is electrically coupled to one of the conductors and the back-end circuit to enable bidirectional signal transmission between the electrode site electrically coupled to the conductor and the back-end circuit.
  • the back-end circuit may refer to the circuit at the back-end of the flexible electrode, such as a signal recording circuit, a signal processing circuit, a signal generation circuit, etc. associated with the signal of the flexible electrode.
  • the backend site layer 306 may be located between at least one of the top insulating layer 302 and the bottom insulating layer 301 and the conductor layer 303 .
  • the flexible electrodes may be coupled to the back-end circuit in a connection manner.
  • the Ball Gate Array (BGA) packaging site as the back-end site may be connected via a printed circuit board ( Printed Circuit Board (PCB), Flexible Printed Circuit (FPC), etc. are transferred to a commercial signal recording system.
  • the flexible electrode can be released from the substrate before transfer (for example, by directly peeling the flexible electrode from the substrate).
  • the flexible electrode can also be integrated with the back-end circuit, that is, the back-end part of the flexible electrode is first connected to the back-end circuit and then is separated from the substrate as a whole.
  • pre-processing functions such as signal amplification and filtering can be integrated on a dedicated chip, and then connected and packaged with an integrated PCB at the back end of the flexible electrode through bonding and other methods to achieve wireless transmission and charging.
  • independent flexible electrodes and independent special-purpose chips as back-end circuits can be used, and the electrical connection between the flexible electrodes and the special-purpose chips can be made through ball mounting patches or ACF Bonding; it can also be used as a back-end circuit.
  • a certain space is reserved on the pre-striped wafer of the terminal circuit chip, and the electrodes are directly produced on this basis, so that joint processing or separate processing of the chip and electrode can be realized to achieve a higher level of integration.
  • the backend sites can have planar dimensions on the micron scale and thicknesses on the nanoscale.
  • the back-end site may be a BGA package site with a diameter of 50 ⁇ m to 2000 ⁇ m, or may be a circular, oval, rectangular, rounded rectangle, or chamfered rectangular site with a side length of 50 ⁇ m to 2000 ⁇ m.
  • the thickness of the dot, back-end site layer 306 and the back-end sites therein may range from 5 nm to 200 ⁇ m. It should be understood that the shape, size, etc. of the rear end site are not limited to the ranges listed above, but can be changed according to design needs.
  • the rear end site for connection may include multiple layers in the thickness direction, and the material of the adhesive layer close to the wire layer 303 in the multiple layers may be a material that can enhance the adhesion between the electrode site and the wire.
  • the material of the soldering flux layer in the middle of the multiple layers can be a soldering flux material
  • the conductive layer in the multiple layers can be other conductive metal materials or non-conducting materials such as the wire layer mentioned above.
  • Metal material, and the outermost layer among the multiple layers that may be exposed through the insulating layers 301 and 302 is an anti-oxidation protective layer.
  • the back-end site layer 306 may be a metal film including three stacked layers, wherein the first layer close to the conductor layer 303 may be a nanometer-scale adhesive layer to improve the back end.
  • the material of the first layer of the adhesion layer may be any one of chromium, tantalum, tantalum nitride, titanium or titanium nitride or a combination thereof.
  • the material of the second layer as the soldering flux layer can be nickel (Ni), Pt or palladium (Pd), and 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 nanotube, PEDOT, etc.
  • the backend site layer can also be made of other conductive metallic materials or non-metallic materials.
  • the back-end site layer 306 in Figure 3 is a part connected to the back-end processing system or chip, and the size, spacing, shape, etc. of its sites can be changed in design according to different connection methods of the back-end.
  • the flexible electrode may not include site layers such as a top electrode site layer, a bottom electrode site layer, a rear end site layer, and the like.
  • the electrode sites on the electrodes and the back-end sites for switching in the back-end portion can both be parts in the wire layer and be electrically coupled to corresponding wires in the wire layer. That is, the flexible electrode may not include the top electrode site layer, the bottom electrode site layer, and the back-end site layer, so the electrode sites and the back-end site are both implemented in the wire layer.
  • electrode sites for sensing and applying electrical signals can be in direct contact with the tissue region into which the electrodes are implanted.
  • each electrode site can be electrically coupled to a corresponding electrode site in the conductor layer.
  • the wires are exposed to the outer surface of the electrode and in contact with biological tissue through corresponding through holes in the top insulating layer or the bottom insulating layer.
  • the back-end sites may also be switched to the back-end circuit through corresponding vias in the top insulating layer or the bottom insulating layer, in which case the flexible electrode may not include a separate backend site layer.
  • the flexible electrode 300 may further include a flexible separation layer 308.
  • the flexible separation layer 308 of the flexible electrode 300 in FIG. 3 is shown as being located at the lowest layer of the entire flexible electrode, that is, but it should be understood that the position of the flexible separation layer is not limited to this, and the flexible electrode may include one or more Flexible separation layers at different locations.
  • a flexible separation layer can be fabricated between the substrate and the bottom insulating layer.
  • the flexible separation layer may be made of a material that can be removed by a specific substance (such as a solution) to separate the two parts of the flexible electrode above and below the flexible separation layer while avoiding damage to the flexible electrode.
  • the material of the flexible separation layer may be metal or non-metal material such as Ni, Cr, aluminum (Al). It should be understood that the flexible separation layer is an optional but not essential part of the flexible electrode and that the flexible electrode can be made directly detachable from the substrate without including the flexible separation layer.
  • the flexible separation layer 308 further includes an adhesive layer, and the material of the adhesive layer may be chromium, tantalum, tantalum nitride, titanium, or titanium nitride.
  • FIG. 4 shows a flowchart of a method 400 of manufacturing a flexible electrode according to an embodiment of the present disclosure.
  • a manufacturing method based on Micro-Electro Mechanical System (MEMS) technology can be used to manufacture nanoscale flexible electrodes.
  • the method 400 may include: at S41 , manufacturing a first insulating layer, a conductor layer and a second insulating layer on the substrate, wherein by patterning in the first insulating layer and the second insulating layer Through holes are created in at least one layer at positions corresponding to the electrode sites; and at S42, the flexible electrode is separated from the substrate.
  • the steps of manufacturing each layer of the flexible electrode at S41 are described in detail below with reference to FIGS. 5 to 7 .
  • FIG. 5 shows a schematic diagram of a method 500 for manufacturing a flexible electrode according to an embodiment of the present disclosure.
  • the attached part and the implanted part of the flexible electrode have the same thickness and are made of the same material, and the flexible electrode at least includes flexible separation. layer, bottom insulation layer, conductor layer, top insulation layer and top electrode site layer.
  • the manufacturing process and structure of the flexible separation layer, bottom insulation layer, conductor layer, top insulation layer, electrode site layer and other parts of the flexible electrode will be described in more detail with reference to FIG. 5 .
  • View (A) of Figure 5 shows the base of the electrode.
  • a hard substrate may be employed, such as glass, quartz, silicon wafer, etc.
  • other soft materials may also be used as the base, such as the same material as the insulating layer.
  • View (B) of Figure 5 shows the steps of fabricating a flexible separation layer over a substrate.
  • the flexible separation layer can be removed by applying specific substances, thereby facilitating the separation of the flexible part of the electrode from the hard substrate.
  • the embodiment shown in Figure 5 uses Ni as the material of the flexible separation layer, but other materials such as Cr and Al can also be used.
  • the flexible separation layer when the flexible separation layer is manufactured on the substrate by evaporation, a portion of the exposed substrate may be etched first, thereby improving the flatness of the entire substrate after evaporation.
  • the flexible separation layer is an optional but not required part of the flexible electrode. Depending on the properties of the chosen material, flexible electrodes can be easily separated without a flexible separation layer.
  • the flexible separation layer may also have markings, which may be used for alignment of subsequent layers.
  • View (C) of Figure 5 shows the fabrication of the bottom insulating layer over the flexible separation layer.
  • the manufacturing of the bottom insulating layer may include steps such as a film forming process, film forming curing, and strengthened curing to produce a thin film as an insulating layer.
  • the film forming process may include coating polyimide on the flexible separation layer, for example, a layer of polyimide may be spin-coated at a stepped rotation speed.
  • Film-forming curing may include gradually increasing the temperature to a higher temperature and maintaining the temperature to form a film for subsequent processing steps.
  • Enhanced curing may include multiple temperature ramps, preferably in a vacuum or nitrogen atmosphere, and baking for several hours before fabricating subsequent layers. It should be understood that the above-mentioned manufacturing process is only a non-limiting example of the manufacturing process of the bottom insulation layer, and one or more steps may be omitted, or more other steps may be included.
  • the above manufacturing process is directed to an embodiment in which the bottom insulating layer in the flexible electrode without the bottom electrode site layer is manufactured and the bottom insulating layer has no through holes corresponding to the electrode sites.
  • the bottom electrode site layer may be fabricated over the flexible separation layer prior to fabricating the bottom insulating layer. For example, Au and Ti can be evaporated sequentially on the flexible separation layer.
  • the patterning steps for the bottom electrode sites will be detailed later for the top electrode sites.
  • a patterning step may also be included for forming the bottom insulating layer corresponding to the bottom electrode site. A through hole is etched at the location. The patterning steps for the insulating layer will be detailed later with respect to the top insulating layer.
  • Views (D) to (G) of Figure 5 show the fabrication of conductor layers on the bottom insulating layer.
  • photoresist and mask can be applied over the bottom insulating layer.
  • other photolithography methods can also be used to prepare patterned films, such as laser direct writing and electron beam lithography.
  • a double layer of glue may be applied to facilitate fabrication (evaporation or sputtering) and peeling off of the patterned film.
  • the exposure may take the form of contact photolithography, in which the mask and the structure are exposed in a vacuum contact mode.
  • different developing solutions and their concentrations may be adopted for graphics of different sizes.
  • This step may also include layer-to-layer alignment.
  • a film can be formed on the structure as shown in view (E), such as evaporation, sputtering and other processes can be used to deposit a metal thin film material, such as Au, to obtain the structure as shown in view (F).
  • peeling can be performed to separate the film in the non-patterned area from the film in the patterned area by removing the photoresist in the non-patterned area, thereby obtaining a structure as shown in view (G), that is, the conductor layer is manufactured.
  • the glue removal process may be performed again after the glue removal stripping to further remove residual glue on the surface of the structure.
  • the backend site layer may also be manufactured.
  • the fabrication process of the backend site layer may be similar to the fabrication process of the metal film described above with respect to the conductor layer.
  • Views (H) to (K) of Figure 5 illustrate the fabrication of the top insulating layer.
  • patterning can generally be achieved directly through patterned exposure and development.
  • patterning cannot be achieved through exposure and development of the insulating layer. Therefore, it can be patterned on top of this layer. Create a thick enough patterned anti-etching layer, and then remove the film in the areas not covered by the anti-etching layer by dry etching (the anti-etching layer will also become thinner, so the anti-etching layer needs to be ensured Thick enough), and then remove the etching resist layer to achieve patterning of the non-photosensitive layer.
  • the insulating layer may be manufactured using photoresist as an etching-resistant layer.
  • the manufacturing of the top insulating layer may include film forming processes, film forming and curing, patterning, enhanced curing and other steps.
  • View (H) shows the structure obtained after the top insulating layer is formed
  • view (I) shows the structure obtained after the top insulating layer is formed.
  • Photoresist and mask are applied on the top insulating layer after film formation.
  • View (J) shows the structure including the etching resist layer obtained after exposure and development.
  • View (K) shows the structure including the prepared The structure of the top insulation layer.
  • the film-forming process, film-forming curing and enhanced curing have been described in detail above for the bottom insulation layer, and are omitted here for the sake of brevity.
  • the patterning step can be performed after film formation and curing, or after enhanced curing. After enhanced curing, the insulating layer has stronger etching resistance.
  • a sufficiently thick layer of photoresist is created on the insulating layer through steps such as glue spreading and baking.
  • the pattern of the top insulating layer 302 shown in FIG. 3 can be achieved by patterning the mask associated with the top insulating layer, that is, on one or more of the conductors of the electrodes extending from the rear end portion.
  • the pattern is transferred to the photoresist on the insulating layer through steps such as exposure and development to obtain an etching-resistant layer, in which the portion that needs to be removed from the top insulating layer is exposed.
  • the exposed portions of the top insulating layer may be removed by oxygen plasma etching to obtain the structure shown in view (K).
  • an adhesion-promoting treatment may also be performed before manufacturing the top insulating layer to improve the bonding force between the bottom insulating layer and the top insulating layer.
  • View (L) of FIG. 5 shows the fabrication of a top electrode site layer by evaporation or the like on the top insulating layer.
  • FIG. 6 shows a schematic diagram of a method 600 for manufacturing a flexible electrode according to an embodiment of the present disclosure.
  • the attached part and the implanted part of the flexible electrode have different thicknesses, and the flexible electrode at least includes a flexible separation layer and a bottom insulation layer. , wire layer, top insulation layer and top electrode site layer.
  • Views (A) to (G) of FIG. 6 illustrating the fabrication of the flexible separation layer, the bottom insulation layer and the conductor layer are similar to views (A) to (G) of FIG. 5 and will not be described again.
  • Views (H) to (K) of Figure 6 illustrate the fabrication of the top insulating layer.
  • Views (H) to (K) of Figure 6 illustrate the fabrication of the top insulating layer.
  • FIG. 6 shows the structure obtained after the top insulating layer is formed.
  • View (I) of FIG. 6 shows the application of photoresist and mask on the top insulating layer after film formation, wherein the pattern of the mask is set to be related to the top insulating layer.
  • View (J) of FIG. 6 shows a structure including an etching resist layer obtained after exposure and development.
  • View (K) of FIG. 6 shows the structure of the top insulating layer after etching. At this time, the thickness of the top insulating layer of the attached part and the implanted part is the same.
  • View (L) of Figure 6 shows the re-application of photoresist and mask on the etched top insulating layer of view (K), where the pattern of the mask is set to coincide with the top of the attached part Insulation layer related, for example, the pattern of the top insulating layer 302 of the attached portion shown in FIG. 3 may be implemented.
  • View (M) of FIG. 6 shows a structure including an etching-resistant layer obtained after exposure and development again. The etching-resistant layer is located on the insulating layer of the attached part to protect the insulating layer of the attached part, and Expose the insulation of the implanted part.
  • View (N) of FIG. 6 shows the final top insulating layer obtained after etching, in which a portion of the insulating layer of the implanted portion is etched away, so that its thickness is smaller than that of the attached portion.
  • View (O) of FIG. 6 shows the fabrication of a top electrode site layer by evaporation or the like on the top insulating layer.
  • FIG. 7 shows a schematic diagram of a method 700 for manufacturing a flexible electrode according to an embodiment of the present disclosure.
  • the attached portion and the implanted portion of the flexible electrode have different thicknesses, and the flexible electrode at least includes a flexible separation layer and a bottom insulation layer. , conductor layer and top insulation layer, but does not include the electrode site layer.
  • Views (A) to (N) of FIG. 7 are similar to views (A) to (N) of FIG. 6 , but it should be noted that, unlike FIGS. 5 and 6 , the mask in view (D) Having patterns related to wires, electrode sites and back-end sites, so that the wire layer of the prepared flexible electrode includes the wires of the flexible electrode, electrode sites for collecting or applying electrical signals and for switching to the backend site of the backend circuit. Also, unlike Figures 5 and 6, the method shown in Figure 7 does not include the step of fabricating the top electrode site layer.
  • the present disclosure provides a flexible electrode for the spinal cord and a manufacturing method thereof. It has both deep and surface structures. It can be attached to the epidural mater and implanted into the spinal cord. It can be used for spinal cord electrical signal collection. Simultaneous recording of epidural and spinal cord LFP and Spike signals can be used for functional electrical stimulation of the spinal cord in the spinal canal and epidural; by proportionally increasing or reducing the size of the electrode, the electrode can be adapted to different human bodies or other vertebrates, and electrodes with different number of layers, different sizes, different shapes, different number of electrode sites, different electrode site arrangements and manufactured by nano-fabrication technology can be designed as needed.
  • the electrodes have good spatial resolution and The high channel count can record a large number of neuronal activities, allowing for further movement decoding and fine limb manipulation; the material used in the flexible electrode can significantly reduce the stiffness of the electrode, which can effectively avoid breakage and provide Long-term stable spinal nerve interface; the material used in this flexible electrode only causes a slight immune response after implantation, and has an ultra-thin structure, which can avoid microenvironment deterioration and surrounding neuron death, further improving its biocompatibility and chronic stability.
  • the flexible electrode has good application prospects and value in neuroscience research and rehabilitation medicine applications.
  • the word "exemplary” means “serving as an example, instance, or illustration” rather than as a “model” that will be accurately reproduced. Any implementation illustratively described herein is not necessarily to be construed as preferred or advantageous over other implementations. Furthermore, the disclosure is not bound by any expressed or implied theory presented in the above technical field, background, brief summary or detailed description.
  • the word “substantially” is meant to include any minor variations resulting from design or manufacturing defects, device or component tolerances, environmental effects, and/or other factors.
  • the word “substantially” also allows for differences from perfect or ideal conditions due to parasitic effects, noise, and other practical considerations that may be present in actual implementations.

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Abstract

本公开涉及一种用于脊髓的柔性电极及其制造方法。提供了一种用于脊髓的柔性电极，所述柔性电极包括：贴附部分，所述贴附部分被配置为能够在硬膜外或硬膜内的白质外侧，并且被配置为在脊髓表面采集或施加电信号；其中，所述柔性电极的贴附部分包括第一绝缘层和第二绝缘层以及位于第一绝缘层和第二绝缘层之间的导线层；其中，所述柔性电极的贴附部分还包括一个或多个电极位点，每个电极位点电耦合到导线层中的导线之一，并且在柔性电极的植入后与脊髓接触，以从脊柱神经采集电信号并通过导线传输采集到的电信号，或向脊柱神经施加通过导线接收到的电信号。

Description

一种用于脊髓的柔性电极及其制造方法
相关申请的交叉引用
本申请是以CN申请号为202210689989.6，申请日为2022年6月17日的申请为基础，并主张其优先权，该CN申请的公开内容在此作为整体引入本申请中。
技术领域
本公开涉及生命科学技术领域，更具体地涉及一种用于脊髓的柔性电极及其制造方法。
背景技术
脊柱神经电极包括硬膜外电极(epidural electrode)和椎管内电极。
发明内容
在下文中给出了关于本公开的简要概述，以便提供关于本公开的一些方面的基本理解。但是，应当理解，这个概述并不是关于本公开的穷举性概述。它并不是意图用来确定本公开的关键性部分或重要部分，也不是意图用来限定本公开的范围。其目的仅仅是以简化的形式给出关于本公开的某些概念，以此作为稍后给出的更详细描述的前序。
根据本公开的第一方面，提供了一种用于脊髓的柔性电极，所述柔性电极包括：贴附部分，所述贴附部分被配置为能够在硬膜外或硬膜内的白质外侧，并且被配置为在脊髓表面采集或施加电信号；其中，所述柔性电极的贴附部分包括第一绝缘层和第二绝缘层以及位于第一绝缘层和第二绝缘层之间的导线层；其中，所述柔性电极的贴附部分还包括一个或多个电极位点，每个电极位点电耦合到导线层中的导线之一，并且在柔性电极的植入后与脊髓接触，以从脊柱神经采集电信号并通过导线传输采集到的电信号，或向脊柱神经施加通过导线接收到的电信号。
根据本公开的第二方面，提供了一种用于脊髓的柔性电极的制造方法，所述柔性电极为根据本公开的第一方面所述的柔性电极，所述方法包括：在基底之上制造第一绝缘层、导线层、第二绝缘层和电极位点；以及从基底分离出柔性电极；其中，通过图形化在第一绝缘层和第二绝缘层中的至少一层的与电极位点对应的位置制造出通 孔。
通过以下参照附图对本公开的示例性实施例的详细描述，本公开的其他特征及其优点将会变得更为清楚。
附图说明
构成说明书的一部分的附图描述了本公开的实施例，并且连同说明书一起用于解释本公开的原理。
参照附图，根据下面的详细描述，可以更清楚地理解本公开，其中：
图1示出了根据本公开的实施例的用于脊髓的柔性电极的至少一部分的示意图；
图2示出了根据本公开的实施例的用于脊髓的柔性电极的至少一部分的植入方式的示意图；
图3示出了根据本公开的实施例的柔性电极的至少一部分的分解图；
图4示出了根据本公开的实施例的制造柔性电极的方法的流程图；
图5示出了根据本公开的实施例的制造柔性电极的方法的示意图；
图6示出了根据本公开的实施例的制造柔性电极的方法的示意图；
图7示出了根据本公开的实施例的制造柔性电极的方法的示意图。
具体实施方式
参考附图进行以下详细描述，并且提供以下详细描述以帮助全面理解本公开的各种示例实施例。以下描述包括各种细节以帮助理解，但是这些细节仅被认为是示例，而不是为了限制本公开，本公开是由随附权利要求及其等同内容限定的。在以下描述中使用的词语和短语仅用于能够清楚一致地理解本公开。另外，为了清楚和简洁起见，可能省略了对公知的结构、功能和配置的描述。本领域普通技术人员将认识到，在不脱离本公开的精神和范围的情况下，可以对本文描述的示例进行各种改变和修改。
以下对至少一个示例性实施例的描述实际上仅仅是说明性的，决不作为对本公开及其应用或使用的任何限制。也就是说，本文中的结构及方法是以示例性的方式示出，以说明本公开中的结构和方法的不同实施例。然而，本领域技术人员将会理解，它们仅仅说明可以用来实施的本公开的示例性方式，而不是穷尽的方式。此外，附图不必按比例绘制，一些特征可能被放大以示出具体组件的细节。
对于相关领域普通技术人员已知的技术、方法和设备可能不作详细讨论，但在适 当情况下，所述技术、方法和设备应当被视为授权说明书的一部分。
在这里示出和讨论的所有示例中，任何具体值应被解释为仅仅是示例性的，而不是作为限制。因此，示例性实施例的其他示例可以具有不同的值。
与椎管内电极相比，由于空间分辨率不理想，硬膜外电极只能记录局部场电位(Local Field Potentials，LFP)信号，椎管内电极则利用较高的空间精度，可以同时记录LFP和单个神经元峰电位(Spike)信号；但目前的椎管内电极同样面临着各种挑战，通道数较低的电极受到记录神经元活动数量的限制，无法充分利用其空间分辨率进行运动解码和精细肢体操作；除了通道计数外，当电极植入于重复变形的脊髓时，由于电极材料刚度引起的物理脆性可能使电极在电气接口和实时解码期间发生断裂并导致不能长期稳定记录；对于刺激而言，刺激精度较低，只能刺激到神经束，距离运动神经较远。
图1示出了根据本公开的实施例的用于脊髓的柔性电极100的至少一部分的示意图。如图1所示，柔性电极100可以包括贴附部分110，该贴附部分110可以被配置为能够在硬膜外或硬膜内的白质外侧，并且被配置为在脊髓表面采集或施加电信号。柔性电极100还可以包括一个或多个植入部分120，该一个或多个植入部分120对称或不对称地布置，各自从贴附部分延伸，可以被配置为能够植入到脊髓内部或与脊髓连接的神经组织(诸如，神经根、神经节等)内部，并且被配置为在脊髓内部的对应位置采集或施加电信号。由于贴附部分110和植入部分120的植入位置及植入方式不同，因此贴附部分110和植入部分120所需实现的强度、贴附性、延展性等可以是不同的。具体而言，贴附部分110和植入部分120可以具有不同厚度，也可以采取不同的材料。当然，贴附部分110和植入部分120也可以具有相同的厚度并采取相同的材料。此外，柔性电极还可以包括后端部分130，该后端部分130可用于接合柔性电极100和后端电路以进行后端转接，贴附部分110可从该后端部分130延伸。该柔性电极100具有良好的柔性，因此当应用于脊髓时可以顺应于所贴附或植入的位置。图1中示出的柔性电极100包括具有细长形状的贴附部分110，以及在贴附部分110的两条长边上对称布置的10个植入部分120。但应理解的是，图1示出的仅仅是非限制性示例，用于脊髓的柔性电极可以根据需要，具有不同形状和尺寸的贴附部分110以及不同数量、形状、尺寸和布置的植入部分120。
虽然图1中示出的柔性电极100包括贴附部分110和植入部分120两者，但应理解的是，本公开中的柔性电极也可以仅包括被配置为能够贴附在硬膜外或硬膜内的贴 附部分而不包括被配置为能够植入到脊髓内部或与脊髓连接的神经组织内部的植入部分。
图2示出了根据本公开的实施例的用于脊髓的柔性电极200的至少一部分的植入方式的示意图，特别是植入后的电极200的放大视图。如图2所示，在将柔性电极200植入到脊柱内时，贴附部分210可以平行于脊柱内的神经束，植入部分220可以与该神经束垂直或相对于垂直方向成一定角度。贴附部分210和每个植入部分220均可以包括一个或多个电极位点，这些电极位点可以用于从脊柱神经采集电信号或向脊柱神经施加电信号。以这样的方式，在将柔性电极200用作记录电极时，贴附部分210的电极位点可以在与其接触硬脊膜上或白质外侧部分记录局部场电位(Local Field Potential，LFP)信号，植入部分220的电极位点可以在与其接触的脊髓神经、神经根以及神经节记录各个神经元的峰电位(Spike)信号，以利用该柔性电极200同时记录局部场电位信号和峰电位信号；以及在将柔性电极200用作刺激电极时，贴附部分210的电极位点可以在与其接触的硬脊膜施加电信号，植入部分220的电极位点可以在与其接触的脊髓施加电信号。图2中示出了将柔性电极200植入到多个脊柱节段的实施例，但应理解的是，本公开不限于此，而是可以根据需要调整柔性电极的尺寸、形状、电极位点的布置等，以使得该柔性电极在植入到一个脊柱节段、多个脊柱节段或所有脊柱节段时适用于一段、多段或全部脊柱神经，以实现对一段脊髓、多段脊髓或所有脊髓中的神经元的电生理信号记录和电刺激功能。
图3示出了根据本公开的实施例的柔性电极300的至少一部分的分解图。从图3可以清楚地看出，柔性电极300为多层结构，具体而言，包括底部绝缘层301、顶部绝缘层302、导线层303、电极位点层304、后端位点层306、柔性分离层308等。应理解的是，图3中示出的柔性电极300的各层仅仅是非限制性示例，本公开中的柔性电极可以省略其中一层或多层，也可以包括更多的其他层。柔性电极300可以包括位于底部的绝缘层301和位于顶部的绝缘层302，具体而言，如图3所示，柔性电极300的贴附部分、植入部分和后端部分可以均包括绝缘层301、302。柔性电极中的绝缘层可以是指电极中起到绝缘作用的外表面层。由于在植入后柔性电极的绝缘层需要与生物组织接触，因此要求绝缘层的材料在具有良好绝缘性的同时具有良好的生物相容性。在本公开的实施例中，绝缘层301、302的材料可以包括聚酰亚胺(Polyimide，PI)、聚二甲基硅氧烷(PDMS)、聚对二甲苯(Parylene)、环氧树脂、聚酰胺酰亚胺(PAI)、SU-8光刻胶、硅胶、硅橡胶等等。在根据本公开的实施例中，为了使得柔性电极进一 步具有生物可降解特性，绝缘层301、302的材料还可以包括聚乳酸、聚乳酸-羟基乙酸共聚物等。此外，绝缘层301、302还是柔性电极300中提供强度的主要部分。绝缘层过薄会降低电极的强度，绝缘层过厚则会降低电极的柔性，并且包括过厚的绝缘层的电极的植入会给生物体带来较大的损伤。在根据本公开的实施例中，绝缘层301、302的厚度可以为100nm至300μm，优选地300nm至20μm。
柔性电极300还可以包括在底部绝缘层301和顶部绝缘层302之间的导线层303中的导线。在根据本公开的实施例中，柔性电极300可以包括同一导线层303中的一个或多个导线，其中，每个导线可以电耦合到电极位点层304中的电极位点并且电耦合到后端位点层306中的后端位点。在本公开的实施例中，导线层303及其中各导线的厚度可以为5nm至200μm。各导线之间的间距例如可以低至10nm。导线的线宽和各导线之间的间距例如可以为10nm至500μm，例如，优选地为100nm至30μm。应理解的是，导线的尺寸等不限于以上列举的范围，而是可以根据设计需要而变化。
在根据本公开的实施例中，导线层303中的导线可以是在厚度方向上包括叠加的多个分层的薄膜结构。这些分层的材料可以为可增强导线的诸如粘附性、延展性、导电性等的材料。作为非限制性示例，导线层303可以是包括叠加的三个分层的金属薄膜，其中，分别与绝缘层301和302接触的第一分层和第二分层为粘附分层，可以采取钛(Ti)、氮化钛(TiN)铬(Cr)、钽(Ta)或氮化钽(TaN)等等金属粘附性材料或非金属粘附性材料，位于第一分层和第二分层之间的第三分层为导电分层，可以采取金(Au)、铂(Pt)、铱(Ir)、钨(W)、铂铱合金、钛合金、石墨、碳纳米管、PEDOT等导电性良好的材料。在根据本公开的实施例中，为了使得柔性电极进一步具有生物可降解特性，导电分层还可以采取镁(Mg)、钼(Mo)及其合金等材料。应理解的是，导线层可以采用具有导电性的其他金属材料或非金属材料制成，也可以采用高分子导电材料以及复合导电材料制成。在根据本公开的实施例中，粘附分层的厚度可以为1nm至50nm，导电分层的厚度可以为5nm至200μm。
柔性电极300还可以包括位于顶部绝缘层302之上的顶部电极位点层304中的电极位点，每个电极位点电耦合到导线层303中的导线之一，并且在柔性电极300的植入后与脊髓接触，以从脊柱神经采集电信号并通过导线传输采集到的电信号，或向脊柱神经施加通过导线接收到的电信号。在图3中示出的柔性电极300中，贴附部分和多个植入部分中的每个植入部分均包括多个相应的电极位点。但应理解的是，本公开不限于此，柔性电极的每个植入部分可以根据需要包括用于在脊髓内部施加或采集信 号多个电极位点，并且柔性电极的贴附部分可以根据需要包括用于在脊髓表面施加或采集信号的多个电极位点。此外，由于每个电极位点耦合到其相应的导线，因此在将柔性电极300用作刺激电极时，其中每个电极位点可以同步或异步地在深部和/或表面的不同位置处施加相同或不同的电信号；而在将柔性电极300用作记录电极时，这些电极位点可以同时精细地采集深部和/或表面的不同位置处的电信号。
在柔性电极300中，顶部电极位点层304中的电极位点可以通过顶部绝缘层302中的与该电极位点相应的位置处的通孔电耦合到相应的导线。在柔性电极包括多个导线的情况下，该柔性电极可以相应地包括顶部电极位点层304中的多个电极位点，并且这些电极位点各自通过顶部绝缘层302中的相应通孔与多个导线之一电耦合。在根据本公开的实施例中，顶部电极位点层304中的电极位点可以是在厚度方向上包括叠加的多个分层的薄膜结构。多个分层中的接近导线层303的粘附分层的材料可以为可增强电极位点与导线的粘附的材料，粘附分层的厚度可以为1nm至50nm。作为非限制性示例，电极位点层304可以是包括叠加的两个分层的金属薄膜，其中，接近导线层303的第一分层为Ti、TiN、Cr、Ta或TaN，电极位点层304的暴露在外的第二分层为Au。应理解的是，电极位点层也可以类似于导线层，采用具有导电性的其他金属材料或非金属材料制成，诸如Pt、Ir、W、Mg、Mo、铂铱合金、钛合金、石墨、碳纳米管、PEDOT等。
各电极位点可以具有微米级的平面尺寸和纳米级的厚度。在根据本公开的实施例中，电极位点的形状可以根据需要设置为各种规则或不规则的形状，数量可以为一个或多个。贴附部分的电极位点最大边长或直径可以为1μm至2mm，各电极位点的间距可以为10μm至20mm。植入部分的电极位点的形状可以根据需要设置为各种规则或不规则的形状，最大边长或直径可以为1μm至500μm，各电极位点之间的间距可以为1μm至5mm。应理解的是，电极位点的形状、数量、大小和间距等可以根据所需记录或刺激的生物组织区域的情况来选择。
在根据本公开的实施例中，电极位点的暴露在外与生物组织接触的表面还可以具有表面改性层，以改善电极位点的电化学特性。作为非限制性示例，表面改性层可以通过利用PEDOT:PSS的电引发聚合涂层、溅射氧化铱薄膜等方法得到，用于在柔性电极采集电信号的情况下降低阻抗(诸如，1kHz工作频率下的电化学阻抗)，以及在柔性电极施加电信号刺激的情况下提高电荷注入能力，从而提高交互效率。
在根据本公开的实施例中，虽然在图3中未示出，但柔性电极还可以包括位于底 部绝缘层301之下的底部电极位点层305中的电极位点，在植入柔性电极后该电极位点可以与生物组织接触以直接采集或施加电信号。与顶部电极位点层304中的电极位点类似地，在柔性电极300中，底部电极位点层305中的电极位点可以通过底部绝缘层301中的与该电极位点相应的位置处的通孔电耦合到相应的导线。在根据本公开的实施例中，底部电极位点层305中的电极位点可以与顶部电极位点层304中的电极位点位于柔性电极300的顶部和底部两侧的相对位置处，并且与位于相对位置的顶部电极位点层304中的电极位点电耦合到导线层303中的同一导线。在根据本公开的实施例中，底部电极位点层305中的电极位点也可以与顶部电极位点层304中的电极位点位于柔性电极300的顶部和底部两侧的不同位置处，以在生物组织的不同区域采集或施加电信号；并且在根据本公开的实施例中，底部电极位点层305中的电极位点也可以电耦合到导线层303中的与顶部电极位点层304中的电极位点不同的导线。
应理解的是，底部电极位点层305是柔性电极的可选而非必要的一部分，例如，本公开中的柔性电极可以仅包括顶部电极位点层304而不包括底部电极位点层305。底部电极位点的形状、尺寸、材料等可以类似于顶部电极位点，在此不再详述。
在本公开的实施例中，柔性电极还可以包括附加的导线层，即，本公开中的柔性电极可以包括一个或多个导线层。附加导线层的尺寸、材料、制造方法等可以类似于导线层303，在此不再详述。在柔性电极包括附加导线层的情况下，这些导线层可以通过附加绝缘层而间隔开，附加绝缘层的尺寸、材料、制造方法可以类似于底部绝缘层301和/或顶部绝缘层302，在此不再详述。这些附加导线层中的一个或多个导线可以通过底部绝缘层、顶部绝缘层、附加绝缘层中的一层或多层中的通孔电耦合到位于底部绝缘层之下或位于顶部绝缘层之上的电极位点。通过在柔性电极中包括多个导线层，可以在相同截面宽度的情况下下提高通过柔性电极传输的信号的数量和精度，即，提供高精度和多通道的电极，有利于实现高通量交互。
在根据本公开的实施例中，柔性电极300的后端部分可以包括后端位点层306中的后端位点，后端位点可以通过底部绝缘层301和/或顶部绝缘层302中的通孔电耦合到导线之一和后端电路，以实现与该导线电耦合的电极位点和后端电路之间的双向信号传输。这里，后端电路可以是指在柔性电极后端的电路，诸如与柔性电极的信号相关联的信号记录电路、信号处理电路、信号生成电路等。优选地，后端位点层306可以位于顶部绝缘层302和底部绝缘层301中的至少一层与导线层303之间。在根据本公开的实施例中，柔性电极可以以连接方式耦合到后端电路，具体而言，作为后端位 点的球栅阵列(Ball Gate Array，BGA)封装位点可以通过印刷电路板(Printed Circuit Board，PCB)、柔性电路板(Flexible Printed Circuit，FPC)等转接至商用的信号记录系统，在转接前可以先将柔性电极从基底释放(例如，通过将柔性电极直接从基底揭下，或通过去除柔性分离层来将柔性电极与基底分离)，通过植球贴片以及异方性导电胶膜键合(Anisotropic Conductive Film Bonding，ACF Bonding)等连接方式将后端部分连接到后端电路，然后使用硅胶等进行封装。在根据本公开的实施例中，柔性电极也可以与后端电路集成，即，先将柔性电极的后端部分连接到后端电路，再整体地从基底分离。具体而言，可以将信号放大和滤波等预处理功能集成在专用芯片上，然后再通过键合等方式与在柔性电极后端的一体化的PCB进行连接和封装，从而实现无线传输和充电等。在这种情况下，可以采用独立的柔性电极和独立的作为后端电路的专用芯片，通过植球贴片或ACF Bonding等方式进行柔性电极和专用芯片之间的电气连接；也可以在作为后端电路的芯片的预先流片好的晶圆上预留出一定空间，在此基础上直接进行电极的制作，从而能够实现芯片和电极的联合加工或分离加工工艺，达到更高的集成度。
后端位点可以具有微米级的平面尺寸和纳米级的厚度。作为非限制性示例，后端位点可以是直径为50μm至2000μm的BGA封装位点，或者可以是边长为50μm至2000μm的圆形、椭圆形、矩形、圆角矩形、倒角矩形的位点，后端位点层306及其中的后端位点的厚度可以为5nm至200μm。应理解的是，后端位点的形状、尺寸等不限于以上列举的范围，而是可以根据设计需要而变化。
用于连接的后端位点可以在厚度方向上包括多个分层，多个分层中的接近导线层303的粘附分层的材料可以为可增强电极位点与导线的粘附的材料，多个分层中的在中间的助焊分层的材料可以为助焊材料，多个分层中的导电分层可以采取如前文所述的导线层的具有导电性的其他金属材料或非金属材料，并且多个分层中的可能通过绝缘层301、302暴露的最外层为防氧化的保护分层。作为非限制性示例，后端位点层306可以是包括叠加的三个分层的金属薄膜，其中，接近导线层303的第一分层可以为纳米量级的粘附分层，以改善后端位点层306与导线层303之间的粘附，作为粘附分层的第一分层的材料可以为铬、钽、氮化钽、钛或氮化钛中的任一种或其组合，作为助焊分层的第二分层的材料可以为镍(Ni)、Pt或钯(Pd)，作为导电分层的第三分层的材料可以为Au、Pt、Ir、W、Mg、Mo、铂铱合金、钛合金、石墨、碳纳米管、PEDOT等。应理解的是，后端位点层也可以采用具有导电性的其他金属材料或非金 属材料制成。图3中的后端位点层306作为与后端处理系统或芯片连接的部分，其位点的大小、间距、形状等可以根据后端的不同连接方式来更换设计。
在根据本公开的实施例中，柔性电极可以不包括诸如顶部电极位点层、底部电极位点层、后端位点层等位点层。在这种情况下，电极上的电极位点和后端部分中用于转接的后端位点可以均为导线层中的部分，并在导线层中电耦合到对应的导线。即，柔性电极可以不包括顶部电极位点层、底部电极位点层、后端位点层，因此电极位点和后端位点均在导线层中实现。并且，用于感测和施加电信号的电极位点可以直接与电极所植入到的组织区域接触，作为非限制性示例，各个电极位点可以在导线层中电耦合到导线层中的相应导线，并通过顶部绝缘层或底部绝缘层中的相应通孔而暴露于电极的外表面并与生物组织接触。类似地，在根据本公开的实施例中，后端位点也可以通过顶部绝缘层或底部绝缘层中的相应通孔而转接到后端电路，在这种情况下柔性电极可以不包括单独的后端位点层。
在根据本公开的实施例中，柔性电极300还可以包括柔性分离层308。图3中的柔性电极300的柔性分离层308被示出为位于整个柔性电极的最底层，即但应理解的是，柔性分离层的位置不限于此，并且柔性电极中可以包括一个或多个位于不同位置的柔性分离层。优选地，柔性分离层可以制造于衬底与底部绝缘层之间。柔性分离层可以采取能够被特定物质(诸如，溶液)去除的材料，以分离柔性电极的在柔性分离层上方及下方的两个部分，同时避免对柔性电极的损伤。在本公开的实施例中，柔性分离层的材料可以是Ni、Cr、铝(Al)等金属或者非金属材料。应理解的是，柔性分离层是柔性电极的可选而非必要的一部分，在不包括柔性分离层的情况下，柔性电极可以被制造为直接可从基底分离。在根据本公开的实施例中，柔性分离层308还包括粘附分层，该粘附分层的材料可以为铬、钽、氮化钽、钛或氮化钛。
图4示出了根据本公开的实施例的制造柔性电极的方法400的流程图。在本公开中，可以采取基于微型电子机械系统(Micro-Electro Mechanical System，MEMS)工艺的制造方法来制造纳米级的柔性电极。如图4所示，方法400可以包括：在S41处，在基底之上制造第一绝缘层、导线层和第二绝缘层，其中，通过图形化在第一绝缘层和第二绝缘层中的至少一层的与电极位点对应的位置制造出通孔；以及在S42处，从基底分离出柔性电极。以下结合图5至图7详述S41处制造柔性电极的各层的步骤。
图5示出了根据本公开的实施例的制造柔性电极的方法500的示意图，该柔性电极中贴附部分和植入部分具有相同的厚度并采取相同的材料，并且该柔性电极至少包 括柔性分离层、底部绝缘层、导线层、顶部绝缘层和顶部电极位点层。结合图5更详细地说明柔性电极的柔性分离层、底部绝缘层、导线层、顶部绝缘层、电极位点层等部分的制造过程和结构。
图5的视图(A)示出了电极的基底。在根据本公开的实施例中，可以采取硬质基底，诸如玻璃、石英、硅晶圆等。在本公开的实施例中，也可以采取其他软质的材料作为基底，诸如采取与绝缘层相同的材料。
图5的视图(B)示出了在基底之上制造柔性分离层的步骤。可以通过施加特定物质来去除柔性分离层，从而方便电极的柔性部分与硬质基底的分离。图5中所示的实施例采用Ni作为柔性分离层的材料，也可以采用Cr、Al等其他材料。在根据本公开的实施例中，在通过蒸镀在基底之上制造柔性分离层时，可以先刻蚀暴露的基底的一部分，从而提高蒸镀后整个基底的平整度。应理解的是，柔性分离层是柔性电极的可选而非必要的一部分。根据所选材料的特性，在没有柔性分离层的情况下也可以方便地分离柔性电极。在根据本公开的实施例中，柔性分离层上还可以具有标记，该标记可以用于后续层的对准。
图5的视图(C)示出了在柔性分离层之上制造底部的绝缘层。作为非限制性示例，在绝缘层采取聚酰亚胺材料的情况下，底部的绝缘层的制造可以包括成膜工艺、成膜固化和加强固化等步骤来制造作为绝缘层的薄膜。成膜工艺可以包括在柔性分离层之上涂敷聚酰亚胺，诸如，可以以分段转速旋涂一层聚酰亚胺。成膜固化可以包括逐步升温至较高温度并保温以成膜，从而进行后续加工步骤。加强固化可以包括在制造后续层之前进行多梯度升温，优选地在有真空或氮气氛围进行升温，并进行若干小时的烘烤。应理解的是，上述制造过程仅仅是底部绝缘层的制造过程的非限制性示例，可以省略其中一个或多个步骤，或可以包括更多其他的步骤。
应注意的是，上述制造过程针对的是制造没有底部电极位点层的柔性电极中的底部绝缘层并且该底部绝缘层中没有与电极位点对应的通孔的实施例。如果柔性电极包括底部电极位点层，则在制造底部绝缘层之前，可以先在柔性分离层之上制造底部电极位点层。诸如，可以在柔性分离层之上依次蒸镀Au以及Ti。底部电极位点的图形化步骤将在后文关于顶部电极位点详述。相应地，在柔性电极包括底部电极位点的情况下，在制造底部绝缘层的过程中，除了上述步骤之外还可以包括图形化步骤，用于在底部绝缘层中的与底部电极位点对应的位置刻蚀出通孔。绝缘层的图形化步骤将在后文关于顶部绝缘层详述。
图5的视图(D)至(G)示出了在底部的绝缘层上制造导线层。如视图(D)所示，可以在底部的绝缘层之上施加光刻胶和掩膜版。应理解的是，也可以采取其他光刻手段进行图形化薄膜的制备，诸如激光直写和电子束光刻等。在根据本公开的实施例中，对于导线层这样的金属薄膜，可以施加双层胶以便于图形化的薄膜的制造(蒸镀或溅射)和剥离。通过设置与导线层相关的掩膜版的图案，例如，可以实现图3中所示的导线层303的图案，即，从后端部分延伸的电极中的一个或多个导线的轮廓。接着，可以进行曝光、显影，得到如视图(E)所示的结构。在根据本公开的实施例中，曝光可以采取接触式光刻，将掩膜版与结构在真空接触模式下曝光。在根据本公开的实施例中，对于不同尺寸的图形，可以采取不同的显影液及其浓度。在该步骤中还可以包括进行层与层的对准。接着，可以在如视图(E)所示的结构上进行成膜，诸如可以使用蒸镀、溅射等工艺，以沉积金属薄膜材料，诸如Au，得到如视图(F)所示的结构。接着，可以进行剥离，通过去除非图形化区域中的光刻胶来将非图形区域的薄膜与图形区的薄膜分离，得到如视图(G)所示的结构，即制造得到导线层。在根据本公开的实施例中，在去胶剥离之后可以再次进行去胶处理，以进一步清除结构表面的残留胶。
在根据本公开的实施例中，在制造导线层之前，还可以制造后端位点层。作为非限制性示例，后端位点层的制造过程可以类似于前文关于导线层所述的金属薄膜的制造过程。
图5的视图(H)至(K)示出了制造顶部的绝缘层。对于光敏型的薄膜，一般可以直接通过图形化曝光和显影实现图形化，而对于绝缘层所采取的非光敏材料，不能通过对其本身进行曝光显影实现图形化，因此，可以在该层之上制造一层足够厚的图形化的抗刻蚀层，然后通过干法刻蚀将抗刻蚀层未覆盖的区域的薄膜去除(同时抗刻蚀层也会变薄，因此需保证抗刻蚀层足够厚)，再将抗刻蚀层去除，以实现非光敏层的图形化。作为非限制性示例，绝缘层的制造可以采用光刻胶作为抗刻蚀层。顶部绝缘层的制造可以包括成膜工艺、成膜固化、图形化、加强固化等步骤，其中，视图(H)示出了顶部绝缘层成膜后得到的结构，视图(I)示出了在成膜后的顶部绝缘层之上施加光刻胶和掩膜版，视图(J)示出了包括曝光、显影后得到的抗刻蚀层的结构，视图(K)示出了包括制得的顶部绝缘层的结构。成膜工艺、成膜固化和加强固化已在前文关于底部绝缘层详述，为简洁起见在此省略。图形化步骤可以在成膜固化后进行，也可以在加强固化后进行，加强固化后绝缘层的抗刻蚀能力更强。具体而言，视图(I) 中通过匀胶、烘烤等步骤，在绝缘层上制造一层足够厚的光刻胶。通过设置与顶部绝缘层相关的掩膜版的图案，例如，可以实现图3中所示的顶部绝缘层302的图案，即，从后端部分延伸的电极中的一个或多个导线上实现的顶部绝缘层的轮廓以及在顶部绝缘层中的与电极位点对应的位置实现的通孔的轮廓。视图(J)中通过曝光、显影等步骤，将图案转移到绝缘层上的光刻胶上，以得到抗刻蚀层，其中，需要从顶部绝缘层中去除的部分被暴露出来。可以通过氧等离子体刻蚀以去除暴露的顶部绝缘层的部分，以得到视图(K)中所示的结构。
在根据本公开的实施例中，还可以在制造顶部绝缘层之前进行增粘处理，以提高底部绝缘层和顶部绝缘层之间的结合力。
图5的视图(L)示出了在顶部绝缘层之上通过蒸镀等方法制造顶部电极位点层。
图6示出了根据本公开的实施例的制造柔性电极的方法600的示意图，该柔性电极中贴附部分和植入部分具有不同的厚度，并且该柔性电极至少包括柔性分离层、底部绝缘层、导线层、顶部绝缘层和顶部电极位点层。
图6的示出柔性分离层、底部绝缘层和导线层的制造的视图(A)至视图(G)类似于图5的视图(A)至视图(G)，在此不再赘述。
图6的视图(H)至(K)示出了制造顶部的绝缘层。为简洁起见，在此不再赘述顶部绝缘层的制造过程中与图5的视图(H)至(K)类似的内容。为了使得贴附部分和植入部分具有不同的厚度，这里将贴附部分和植入部分的顶部绝缘层制造为不同的厚度。图6的视图(H)示出了顶部绝缘层成膜后得到的结构。图6的视图(I)示出了在成膜后的顶部绝缘层之上施加光刻胶和掩膜版，其中，掩膜版的图案被设置为与顶部绝缘层相关，例如，可以实现图3中所示的顶部绝缘层302的图案，即，从后端部分延伸的电极中的一个或多个导线上实现的顶部绝缘层的轮廓以及在顶部绝缘层中的与电极位点对应的位置实现的通孔的轮廓。图6的视图(J)示出了包括曝光、显影后得到的抗刻蚀层的结构。图6的视图(K)示出了刻蚀后的顶部绝缘层的结构，此时，贴附部分和植入部分的顶部绝缘层的厚度相同。图6的视图(L)示出了在视图(K)的刻蚀后的顶部绝缘层上再次施加光刻胶和掩膜版，其中，掩膜版的图案被设置为与贴附部分的顶部绝缘层相关，例如，可以实现图3中所示的贴附部分的顶部绝缘层302的图案。图6的视图(M)示出了包括再次曝光、显影后得到的抗刻蚀层的结构，该抗刻蚀层位于贴附部分的绝缘层之上，以保护贴附部分的绝缘层，并暴露植入部分的绝缘层。图6的视图(N)示出了刻蚀之后得到的最终的顶部绝缘层，其中， 植入部分的绝缘层被刻蚀掉一部分，因此其厚度小于贴附部分的绝缘层。
图6的视图(O)示出了在顶部绝缘层之上通过蒸镀等方法制造顶部电极位点层。
图7示出了根据本公开的实施例的制造柔性电极的方法700的示意图，该柔性电极中贴附部分和植入部分具有不同的厚度，并且该柔性电极至少包括柔性分离层、底部绝缘层、导线层和顶部绝缘层，但不包括电极位点层。
图7的视图(A)至视图(N)类似于图6的视图(A)至视图(N)，但应注意的是，不同于图5和图6，视图(D)中的掩膜版具有与导线、电极位点以及后端位点相关的图案，从而使得制得的柔性电极的导线层中包括该柔性电极的导线、用于采集或施加电信号的电极位点和用于转接到后端电路的后端位点。并且，不同于图5和图6，图7所示的方法不包括制造顶层电极位点层的步骤。
本公开提供了一种用于脊髓的柔性电极及其制造方法，其同时具备深部与表面结构，既可以贴附于硬膜外，又可以植入脊髓内，既可以用于脊髓电信号采集，同时记录硬膜外和脊髓LFP和Spike信号，又可以用于在椎管内和硬膜外对脊髓进行功能电刺激；通过按比例增大或缩小电极的尺寸，可以使该电极适用于不同人体或其它脊椎动物，并且可以根据需要设计具有不同层数、不同尺寸、不同形状、不同电极位点数量、不同电极位点布置并且采取纳米制造技术制造的电极，该电极具有良好的空间分辨率和高通道数，能够记录大量神经元活动，从而进一步进行运动解码和精细肢体操作；该柔性电极所采取的材料能够显著降低电极的刚度，在应用于重复变形的脊髓时，能够有效避免断裂并提供长期稳定的脊柱神经界面；该柔性电极所采取的材料在植入后仅引起轻微的免疫反应，同时具备超薄结构，能够避免微环境恶化和周围神经元死亡，进一步提高了其生物相容性和慢性稳定性。
该柔性电极在神经科学的研究和康复医学的应用中具有良好的应用前景和价值。
在说明书及权利要求中的词语“前”、“后”、“顶”、“底”、“之上”、“之下”等，如果存在的话，用于描述性的目的而并不一定用于描述不变的相对位置。应当理解，这样使用的词语在适当的情况下是可互换的，使得在此所描述的本公开的实施例，例如，能够在与在此所示出的或另外描述的那些取向不同的其他取向上操作。
如在此所使用的，词语“示例性的”意指“用作示例、实例或说明”，而不是作为将被精确复制的“模型”。在此示例性描述的任意实现方式并不一定要被解释为比其他实现方式优选的或有利的。而且，本公开不受在上述技术领域、背景技术、发明内容或具体实施方式中所给出的任何所表述的或所暗示的理论所限定。
如在此所使用的，词语“基本上”意指包含由设计或制造的缺陷、器件或元件的容差、环境影响和/或其他因素所致的任意微小的变化。词语“基本上”还允许由寄生效应、噪声以及可能存在于实际的实现方式中的其他实际考虑因素所致的与完美的或理想的情形之间的差异。
仅仅为了参考的目的，可以在本文中使用“第一”、“第二”等类似术语，并且因而并非意图限定。例如，除非上下文明确指出，否则涉及结构或元件的词语“第一”、“第二”和其他此类数字词语并没有暗示顺序或次序。
还应理解，“包括/包含”一词在本文中使用时，说明存在所指出的特征、整体、步骤、操作、单元和/或组件，但是并不排除存在或增加一个或多个其他特征、整体、步骤、操作、单元和/或组件以及/或者它们的组合。
如本文所使用的，术语“和/或”包括相关联的列出项目中的一个或多个的任何和所有组合。本文中使用的术语只是出于描述特定实施例的目的，并不旨在限制本公开。如本文中使用的，单数形式“一”、“一个”和“该”也旨在包括复数形式，除非上下文另外清楚指示。
本领域技术人员应当意识到，在上述操作之间的边界仅仅是说明性的。多个操作可以结合成单个操作，单个操作可以分布于附加的操作中，并且操作可以在时间上至少部分重叠地执行。而且，另选的实施例可以包括特定操作的多个实例，并且在其他各种实施例中可以改变操作顺序。但是，其他的修改、变化和替换同样是可能的。因此，本说明书和附图应当被看作是说明性的，而非限制性的。
虽然已经通过示例对本公开的一些特定实施例进行了详细说明，但是本领域的技术人员应该理解，以上示例仅是为了进行说明，而不是为了限制本公开的范围。在此公开的各实施例可以任意组合，而不脱离本公开的精神和范围。本领域的技术人员还应理解，可以对实施例进行多种修改而不脱离本公开的范围和精神。本公开的范围由所附权利要求来限定。

Claims (31)

  1. 一种用于脊髓的柔性电极，所述柔性电极包括贴附部分，所述贴附部分被配置为能够贴附在硬膜外或硬膜内的白质外侧，并且被配置为在脊髓表面采集或施加电信号；
    其中，所述柔性电极的贴附部分包括第一绝缘层和第二绝缘层以及位于第一绝缘层和第二绝缘层之间的导线层；
    其中，所述柔性电极的贴附部分还包括一个或多个电极位点，每个电极位点电耦合到导线层中的导线之一，并且在柔性电极的植入后与脊髓接触，以从脊柱神经采集电信号并通过导线传输采集到的电信号，或向脊柱神经施加通过导线接收到的电信号。
  2. 根据权利要求1所述的柔性电极，其中，所述柔性电极还包括一个或多个植入部分，所述一个或多个植入部分各自从所述贴附部分延伸，被配置为能够植入到脊髓内部或与脊髓连接的神经组织内部，并且被配置为在脊髓内部的对应位置采集或施加电信号；
    其中，所述植入部分包括第一绝缘层和第二绝缘层以及位于第一绝缘层和第二绝缘层之间的导线层；
    其中，所述植入部分还包括一个或多个电极位点，每个电极位点电耦合到导线层中的导线之一，并且在柔性电极的植入后与脊髓接触，以从脊柱神经采集电信号并通过导线传输采集到的电信号，或向脊柱神经施加通过导线接收到的电信号；以及
    其中，所述柔性电极的贴附部分和植入部分具有相同或不同的厚度，采取相同或不同的材料。
  3. 根据权利要求1或2所述的柔性电极，其中：
    所述柔性电极包括多个导线层，所述多个导线层之间通过附加绝缘层而间隔开，并且每个导线层中包括彼此间隔开的多个导线。
  4. 根据权利要求1或2所述的柔性电极，其中：
    所述电极位点位于第一绝缘层和第二绝缘层中的至少一层的外侧的电极位点层中，并通过所述至少一层中的通孔电耦合到导线层中的导线。
  5. 根据权利要求4所述的柔性电极，其中，所述电极位点包括导电分层，所述导电分层的材料为金、铂、铱、钨、镁、钼、铂铱合金、钛合金、石墨、碳纳米管、PEDOT中的任一种或其组合。
  6. 根据权利要求5所述的柔性电极，其中，所述电极位点还包括靠近导线层的粘附分层，所述粘附分层采取能够增强电极位点与导线层的粘附的材料。
  7. 根据权利要求3所述的柔性电极，其中：
    所述电极位点位于导线层中并通过第一绝缘层和第二绝缘层中的至少一层中的通孔暴露。
  8. 根据权利要求2所述的柔性电极，其中，所述电极位点的形状根据需要设置，数量为一个或多个，其中：
    贴附部分的电极位点的最大边长或直径为1微米至2毫米，各电极位点的间距为10微米至20毫米；
    植入部分的电极位点的最大边长或直径为1微米至500微米，各电极位点的间距为1微米至5毫米。
  9. 根据权利要求1或2所述的柔性电极，还包括后端部分，其中：
    所述贴附部分从所述后端部分延伸，以及
    所述后端部分包括后端位点，所述后端位点耦合到导线层中的导线之一和后端电路，以实现与所述导线之一电耦合的电极位点和后端电路之间的双向信号传输。
  10. 根据权利要求9所述的柔性电极，其中，在将所述后端部分耦合到所述后端电路后从所述柔性电极的基底分离，或在将所述柔性电极从基底分离之后将所述后端部分耦合到所述后端电路。
  11. 根据权利要求9所述的柔性电极，其中：
    所述后端位点位于导线层中并通过第一绝缘层和第二绝缘层中的至少一层中的 通孔转接到后端电路；或者
    所述后端位点位于第一绝缘层和第二绝缘层中的至少一层与导线层之间的后端位点层中，并通过所述至少一层中的通孔电耦合到导线层中的导线。
  12. 根据权利要求9所述的柔性电极，其中，所述后端位点包括导电分层，所述导电分层的材料为金、铂、铱、钨、镁、钼、铂铱合金、钛合金、石墨、碳纳米管、PEDOT中的任一种或其组合。
  13. 根据权利要求9所述的柔性电极，其中，后端位点的厚度为5纳米至200微米。
  14. 根据权利要求12所述的柔性电极，其中，所述后端位点还包括靠近导线层的粘附分层，所述粘附分层的材料为铬、钽、氮化钽、钛或氮化钛中的任一种或其组合。
  15. 根据权利要求1或2所述的柔性电极，其中，所述导线层包括导电分层，所述导电分层的材料为金、铂、铱、钨、铂铱合金、钛合金、石墨、碳纳米管、PEDOT中的任一种或其组合。
  16. 根据权利要求15所述的柔性电极，其中，所述导电分层的厚度为5纳米至200微米。
  17. 根据权利要求9所述的柔性电极，其中，所述导线层包括导电分层和靠近电极位点和后端位点中的任一者的粘附分层，所述粘附分层的材料为铬、钽、氮化钽、钛或氮化钛中的任一种或其组合。
  18. 根据权利要求1或2所述的柔性电极，其中，第一绝缘层和第二绝缘层的厚度为100纳米至300微米。
  19. 根据权利要求1或2所述的柔性电极，其中，第一绝缘层和第二绝缘层的 材料为聚酰亚胺、聚二甲基硅氧烷、聚对二甲苯、环氧树脂、聚酰胺酰亚胺、SU-8光刻胶、硅胶、硅橡胶中的任一种或其组合。
  20. 根据权利要求1或2所述的柔性电极，还包括柔性分离层，其中，所述柔性分离层能够被特定物质去除以分离柔性电极的部分并避免对柔性电极的损伤。
  21. 根据权利要求20所述的柔性电极，其中，所述柔性分离层的材料为镍、铬、铝中的任一种或其组合。
  22. 根据权利要求20所述的柔性电极，其中，所述柔性分离层还包括粘附分层，所述粘附分层的材料为铬、钽、氮化钽、钛或氮化钛。
  23. 根据权利要求2所述的柔性电极，其中，所述贴附部分平行于脊柱内的神经束，并且所述植入部分与所述神经束垂直或相对于垂直方向成一定角度。
  24. 根据权利要求2所述的柔性电极，其中：
    所述贴附部分的电极位点被配置为能够在硬膜外或硬膜内白质外侧记录局部场电位信号，所述植入部分的电极位点被配置为能够在神经根、神经节以及脊髓内部记录各个神经元的峰电位信号，以利用所述柔性电极同时记录局部场电位信号和峰电位信号；以及
    所述贴附部分的电极位点被配置为能够在硬膜外或硬膜内白质外侧施加电信号，所述植入部分的电极位点被配置为能够在神经根、神经节以及脊髓内部部分施加电信号。
  25. 根据权利要求2所述的柔性电极，其中，所述柔性电极包括细长的贴附部分和从所述贴附部分的相对的两个长边延伸的多个植入部分。
  26. 根据权利要求25所述的柔性电极，其中，所述多个植入部分在所述两个长边上对称或不对称地布置。
  27. 根据权利要求1或2所述的柔性电极，其中，导线层的材料为镁、钼及其合金中的任一种或其组合，第一绝缘层和第二绝缘层的材料为聚乳酸、聚乳酸-羟基乙酸共聚物中的任一种或其组合，以使得所述柔性电极生物可降解。
  28. 根据权利要求1或2所述的柔性电极，其中，所述柔性电极被配置为能够用于一个脊柱节段、多个脊柱节段或所有脊柱节段，从而对一个脊柱节段、多个脊柱节段或所有脊柱节段中的神经元分别采集或施加电信号。
  29. 一种用于脊髓的柔性电极的制造方法，所述柔性电极为如权利要求1-28中的任一项所述的柔性电极，所述方法包括：
    在基底之上制造第一绝缘层、导线层、第二绝缘层和电极位点；以及
    从基底分离出柔性电极；
    其中，通过图形化在第一绝缘层和第二绝缘层中的至少一层的与电极位点对应的位置制造出通孔。
  30. 根据权利要求29所述的制造方法，其中：
    所述电极位点被制造为位于导线层中并通过第一绝缘层和第二绝缘层中的至少一层中的通孔暴露；或者
    所述电极位点被制造为位于第一绝缘层和第二绝缘层中的至少一层的外侧的电极位点层中，并通过所述至少一层中的通孔电耦合到导线层中的导线。
  31. 根据权利要求29所述的制造方法，其中：
    所述后端位点被制造为位于导线层中并通过第一绝缘层和第二绝缘层中的至少一层中的通孔转接到后端电路；或者
    所述后端位点被制造为位于第一绝缘层和第二绝缘层中的至少一层与导线层之间的后端位点层中，并通过所述至少一层中的通孔电耦合到导线层中的导线。
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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110237921A1 (en) * 2009-09-23 2011-09-29 Ripple Llc Systems and methods for flexible electrodes
CN108751116A (zh) * 2018-05-08 2018-11-06 上海交通大学 用于生物电记录或电刺激的翘曲型柔性电极及其制备方法
CN110947094A (zh) * 2019-12-26 2020-04-03 东南大学 一种植入贴敷式神经电信号采集和功能电刺激电极阵列
CN112386262A (zh) * 2020-11-18 2021-02-23 中国科学院半导体研究所 U型柔性电极植入系统及其制备方法

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110237921A1 (en) * 2009-09-23 2011-09-29 Ripple Llc Systems and methods for flexible electrodes
CN108751116A (zh) * 2018-05-08 2018-11-06 上海交通大学 用于生物电记录或电刺激的翘曲型柔性电极及其制备方法
CN110947094A (zh) * 2019-12-26 2020-04-03 东南大学 一种植入贴敷式神经电信号采集和功能电刺激电极阵列
CN112386262A (zh) * 2020-11-18 2021-02-23 中国科学院半导体研究所 U型柔性电极植入系统及其制备方法

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
ZHUANG-HUI ZHU, ZHOU LIANG, ZHANG HUA ,LI GANG, JIN QING-HUI, ZHAO JIAN-LONG: "Fabrication of Carbon Film-Based Flexible Neural Microelectrode Array", NANOTECHNOLOGY AND PRECISION ENGINEERING, vol. 10, no. 2, 15 March 2012 (2012-03-15), pages 184 - 188, XP093117554, DOI: 10.13494/j.npe.2012.033 *

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