WO2023240693A1 - 一种用于周围神经的柔性电极及其制造方法 - Google Patents

一种用于周围神经的柔性电极及其制造方法 Download PDF

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Publication number
WO2023240693A1
WO2023240693A1 PCT/CN2022/102335 CN2022102335W WO2023240693A1 WO 2023240693 A1 WO2023240693 A1 WO 2023240693A1 CN 2022102335 W CN2022102335 W CN 2022102335W WO 2023240693 A1 WO2023240693 A1 WO 2023240693A1
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Prior art keywords
flexible electrode
layer
electrode
flexible
insulating layer
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PCT/CN2022/102335
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English (en)
French (fr)
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李雪
赵郑拓
李肖城
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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 WO2023240693A1 publication Critical patent/WO2023240693A1/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
    • A61B5/48—Other medical applications
    • A61B5/4836—Diagnosis combined with treatment in closed-loop systems or methods
    • 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
    • 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
    • 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
    • A61N1/36128—Control systems
    • A61N1/36135—Control systems using physiological parameters
    • 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 field of life science technology, and more specifically to a flexible electrode for peripheral nerves and a manufacturing method thereof.
  • Nerve electrodes can be used to control peripheral nerves in amputated limbs.
  • a flexible electrode for peripheral nerves including a flexible electrode that is implantable into an amputated peripheral nerve or nerve stump and configured to collect within and on the surface of a peripheral nerve bundle or An implanted part that applies an electrical signal
  • 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
  • the implanted part includes one or more Each electrode site is electrically coupled to one of the wires in the wire layer and contacts the peripheral nerves after the flexible electrode is implanted to collect electrical signals from the peripheral nerves and transmit the collected electrical signals through the wires.
  • the implanted part has holes to facilitate the reconstruction of the peripheral nerves and to be in close contact with the peripheral nerves after reconstruction.
  • a method for manufacturing a flexible electrode for peripheral nerves comprising: on a substrate manufacturing a first insulating layer, a conductor layer, a second insulating layer and an electrode site; and separating a flexible electrode from a substrate; wherein, by patterning at least one layer of the first insulating layer and the second insulating layer with the electrode site Create through holes at the corresponding points.
  • FIG. 1 illustrates an exploded view of at least a portion of a flexible electrode for peripheral nerves in accordance with an embodiment of the present disclosure
  • FIG. 2 illustrates an enlarged view of at least a portion of a lead and electrode site at an implanted portion of a flexible electrode for peripheral nerves in accordance with an embodiment of the present disclosure
  • FIG. 3 illustrates an enlarged view of at least a portion of an extension of a lead and electrode site at an implanted portion of a flexible electrode for peripheral nerves in accordance with an embodiment of the present disclosure
  • FIG. 4 illustrates an exploded view of at least a portion of a flexible electrode for peripheral nerves in accordance with an embodiment of the present disclosure
  • FIG. 5 illustrates an enlarged view of at least a portion of a lead and electrode site at an implanted portion of a flexible electrode for peripheral nerves in accordance with an embodiment of the present disclosure
  • FIG. 6 illustrates an enlarged view of at least a portion of a lead and an electrode site of an extension of an implanted portion of a flexible electrode for peripheral nerves in accordance with an embodiment of the present disclosure
  • FIG. 7 illustrates an enlarged view of an extended portion and an inner annular portion of an implanted portion of a flexible electrode for peripheral nerves in accordance with an embodiment of the present disclosure
  • FIG. 8 illustrates a flow chart of a method of manufacturing a flexible electrode for peripheral nerves in accordance with an embodiment of the present disclosure
  • FIG. 9 shows a schematic diagram of a method of manufacturing a flexible electrode for peripheral nerves according to an embodiment of the present disclosure
  • FIG. 10 shows a schematic diagram of an implantation manner of a flexible electrode for peripheral nerves according to an embodiment of the present disclosure
  • Figure 11 shows a schematic diagram of an implantation manner of a flexible electrode for peripheral nerves according to an embodiment of the present disclosure
  • Figure 12 shows a schematic diagram of the deformation of an implanted portion of a flexible electrode according to an embodiment of the present disclosure
  • Figure 13 shows a schematic diagram of a method for manufacturing a flexible electrode for peripheral nerves 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.
  • Extrafascicular nerve electrodes When applied, extrafascicular nerve electrodes are usually wrapped around the outside of the peripheral nerve bundle. Usually the number of sites is less than 10. They can only record local field potential signals, and due to the existence of immune scars, they cannot stably record and stimulate for a long time.
  • Extrafascicular neural electrodes include Cuff electrodes, FINE electrodes, and flexible Helical electrodes. During use, the extrafascicular nerve electrode is assembled on the inner wall of a silicone hose or flat catheter, and then the silicone hose or flat catheter is wrapped around the outside of the nerve bundle.
  • the silicone hose wrapped around the outside of the nerve of the extra-bundle nerve electrode may be displaced relative to the nerve bundle; and during long-term use, friction between the hard catheter and the nerve bundle may cause damage to the nerve.
  • the scar formed on the nerve will affect the recording and stimulation of the signal; the extra-fascicular nerve electrode can only record the compound action potential signal and perform a wide range of nerve stimulation, and the recording and stimulation accuracy is far from meeting the needs of fine control; in addition, the electrode The recorded resolution is also lower.
  • Intrafascicular nerve electrodes usually arrange the electrode recording ends on a long strip base and insert the base into the nerve bundle.
  • Commonly used intrafascicular nerve electrodes include hard Utah electrodes, floating electrodes, and Michigan electrodes. Intrafascicular electrodes are implanted in peripheral nerve bundles and can simultaneously record action potentials and local field potential signals.
  • hard electrodes can cause greater tissue damage, leading to local aggregation of glial cells around the electrodes, and the tips of hard electrodes are relatively brittle. , easy to fall off and break, resulting in inability to record and stimulate stably for a long time.
  • the current bottleneck of related technologies is how to provide long-term and stable multi-channel control signals. Specifically, it is necessary to directly control the peripheral nerves of amputated limbs to have the potential to output high-throughput fine control signals and receive signals including temperature, pressure, and pain. complex sensory signals within. Therefore, there is an urgent need for a peripheral nerve electrode with high channel count, high selectivity, ultra-flexibility, and capable of long-term stable recording and stimulation.
  • Figure 1 shows an exploded view of at least a portion of a flexible electrode 100 for peripheral nerves in accordance with an embodiment of the present disclosure.
  • the flexible electrode 100 takes advantage of the characteristic that peripheral nerves can be reconstructed and can be implanted into two completely amputated nerves.
  • the flexible electrode 100 actively forms a tight electrode tissue interface with the electrode to achieve signal recording and measurement. Superior performance to intrafascicular and extrafascicular neural electrodes as described above.
  • the flexible electrode 100 may include an implant portion 110 that may be implanted into an amputated peripheral nerve or nerve stump and configured to collect or apply electrical signals within and on the surface of the peripheral nerve bundle.
  • Implant portion 110 may be porous and stretchable. The porosity and stretchability of the implanted portion 110 can facilitate the reconstruction of the peripheral nerve into which it is implanted, and allow the implanted portion 110 to be in close contact with the peripheral nerve after reconstruction.
  • the shape and size of the pores can be designed according to the size of the peripheral nerves, and the porosity of the implanted part 110 is more than 70%.
  • the implant portion 110 may include an outer annular portion 111 and one or more extension portions 112 extending inwardly from the outer annular portion 111 .
  • the six extension portions 112 symmetrically extend serpentinely inwardly from the outer annular portion 111 and are parallel to each other so as to be between the outer annular portion 111 and the one or more extension portions 112 Apertures are formed, but it should be understood that the shape, number and arrangement of the extensions are not limited thereto.
  • the extension portion 412 extends linearly inward, and this embodiment will be described in detail below.
  • these extending portions 112 may also be asymmetric or non-parallel to each other.
  • the outer annular portion 111 can surround the reconstructed peripheral nerve, and one or more extension portions 112 can extend from the outer annular portion 111 toward the inside of the peripheral nerve and deform as the peripheral nerve is reconstructed.
  • one or more extension portions 112 can be stretched longer due to the reconstruction of the peripheral nerve and thus maintain close contact with the peripheral nerve.
  • the serpentine structure of the extension portion 112 and the flexibility of the flexible electrode 100 Materials can facilitate this deformation.
  • the one or more extension portions 112 may conform to the reconstruction of the peripheral nerve and have a different arrangement than the arrangement in which the flexible electrode 100 was originally manufactured.
  • the one or more extension portions 112 may not be in the same plane. And are not parallel to each other, but may extend in different directions or angles from the outer annular portion 111.
  • the two extending portions 112 shown as collinear in the same plane in Figure 1 may form a certain angle.
  • one or more extensions 112 may be dipped in a biocompatible adhesive (such as, but not limited to, low modulus silicone) so that the one or more extensions 112 Or multiple extension parts 112 are coated with biocompatible adhesive to provide waterproofing.
  • a biocompatible adhesive such as, but not limited to, low modulus silicone
  • the extension part is shown as linear or serpentine, but it should be understood that the flexible electrode according to the present disclosure is not limited thereto, and the extension part may also take the shape of a horseshoe, a wheel, or a serpentine shape. Strip, strip, mesh and other shapes.
  • the flexible electrode 100 may further include a rear end portion 120, which may be implanted subcutaneously and used to couple the flexible electrode 100 and the rear end circuit to perform rear end transfer, implantation Portion 110 extends from the rear end portion 120 .
  • the flexible electrode 100 shown in Figure 1 includes an implant portion 110 having a circular profile and an elongated rear end portion 120, but it should be understood that Figure 1 shows only a non-limiting example for peripheral nerve bundles.
  • the flexible electrode can have the implant portion 110 and the rear end portion 120 of different shapes and sizes as needed.
  • the flexible electrode 100 has a multi-layer structure, specifically, including a bottom insulating layer 101, a top insulating layer 102, a conductor layer 103, an electrode site layer 104, a back-end site layer 106, a flexible Separation layer 108 etc. It should be understood that the layers of the flexible electrode 100 shown in FIG. 1 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 100 may include an insulating layer 101 on the bottom and an insulating layer 102 on the top. Specifically, as shown in FIG. 1 , the implant portion 110 and the rear end portion 120 of the flexible electrode 100 may each include insulating layers 101 , 102 .
  • 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 101 and 102 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 101 and 102 may also include polylactic acid, polylactic acid-glycolic acid copolymer, and the like.
  • the insulating layers 101, 102 are also the main part of the flexible electrode 100 that provide strength.
  • the thickness of the insulating layers 101, 102 may be 100 nm to 300 ⁇ m.
  • the outer annular portion 111 of the flexible electrode 100 may be thickened compared to other portions (such as the extension portion 112 or the like) to provide higher strength.
  • at least one of the bottom insulating layer 101 and the top insulating layer 102 at the outer annular portion 111 may be thickened.
  • the flexible electrode 100 may also include wires in the wire layer 103 between the bottom insulating layer 101 and the top insulating layer 102 .
  • the implant portion 110 and the rear end portion 120 of the flexible electrode 100 may each include a wire layer 103 .
  • these wires extend along the rear end portion 120 to the implant portion 120 and in the implant portion 120 along at least a portion of the outer annular portion 111 and one of the extension portions 112 to a position extending Part 112 of electrode sites.
  • the flexible electrode 100 may include one or more conductors in the same conductor layer 103 , wherein each conductor may be electrically coupled to an electrode site in the electrode site layer 104 and to a rear Backend sites in endsite layer 106.
  • Each wire may have a width on the micron scale and a thickness on the nanoscale.
  • the thickness of the wire layer 103 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 103 may be a thin film structure including a plurality of stacked layers in the thickness direction. These layered materials may be materials that enhance the conductor's properties such as adhesion, extensibility, conductivity, etc.
  • the conductor layer 103 may be a metal film including three stacked layers, wherein the first layer and the second layer in contact with the insulating layers 101 and 102 respectively are adhesive layers, which may be Metal adhesive materials or non-metal adhesive materials such as titanium (Ti), titanium nitride (TiN), chromium (Cr), tantalum (Ta) or tantalum nitride (TaN) 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. In embodiments according to the present disclosure, the thickness of the adhesion layer may be 1 nm to 50 nm.
  • the flexible electrode 100 may also include electrode sites in a top electrode site layer 104 located above the top insulating layer 102 , each electrode site being electrically coupled to one of the conductors in the conductor layer 103 and implanted on the flexible electrode 100 . After entering, it makes contact with the peripheral nerves to collect electrical signals from the peripheral nerves and transmit the collected electrical signals through the wires, or to apply the electrical signals received through the wires to the peripheral nerves.
  • each of the six extension portions 112 in the implant portion 110 includes a plurality of corresponding electrode sites, with electrode sites closer to the outer annular portion 111 It can be used to apply or collect signals on the surface of peripheral nerves, and electrode sites farther away from the outer annular portion 111 can be used to apply or collect signals inside the peripheral nerves.
  • each extended portion of the flexible electrode may include a plurality of electrode sites for applying or collecting signals within and on the surface of peripheral nerves as desired.
  • each electrode site is coupled to its corresponding lead, when flexible electrode 100 is used as a stimulating electrode, each electrode site may synchronously or asynchronously operate at different locations deep and/or superficially on the peripheral nerve surface. The same or different electrical signals are applied at the locations; and when the flexible electrode 100 is used as a recording electrode, these electrode sites can simultaneously and precisely collect electrical signals at different locations deep and/or on the surface of the peripheral nerve.
  • FIG. 2 illustrates an enlarged view of at least a portion of a lead and electrode site at an implanted portion of a flexible electrode for peripheral nerves, which is the implanted portion shown in FIG. 1 , in accordance with an embodiment of the present disclosure.
  • wires 213 extend along at least a portion of the outer annular portion of the implant portion and then snake along the extended portion of the implant portion and are electrically coupled to corresponding electrode sites 214 .
  • the wires 213 may be located in different layers from the electrode sites 214, such that the wires 213 are located in the wire layer 103 as shown in FIG.
  • the electrode sites 214 are located in the top electrode site layer as shown in FIG. In 104; the wire 213 may also be located in the same layer as the electrode site 214, that is, the flexible electrode may not include an electrode site layer, and both the wire and the electrode site are located in the wire layer between the top insulating layer and the bottom insulating layer, And the electrode site 214 is exposed to the outer surface of the electrode and in contact with the peripheral nerve through the through hole in at least one of the top insulation layer and the bottom insulation layer.
  • each extension part may include a plurality of conductive wires 313 extending in a serpentine shape and a corresponding plurality of electrode sites 314 , wherein each electrode site 314 is coupled to its corresponding one conductive wire 313 , and each conductive wire 313 are spaced apart from each other and extend in a serpentine manner parallel to each other.
  • an electrode site in the top electrode site layer 104 can be electrically coupled to a corresponding wire through a via hole in the top insulating layer 102 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 104 , and the electrode sites are each connected to a plurality of electrode sites through corresponding through holes in the top insulating layer 102 .
  • One of the conductors is electrically coupled.
  • the electrode sites in the top electrode site layer 104 may be a thin film structure including a plurality of superimposed layers in the thickness direction.
  • the material of the adhesion layer close to the wire layer 103 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 104 may be a metal film including two superimposed layers, wherein the first layer close to the wire layer 103 is Ti, TiN, Cr, Ta or TaN, and the electrode site layer The exposed second layer of 104 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, the number can be one or more, the maximum side length or diameter can be 1 ⁇ m to 500 ⁇ m, and each electrode site
  • the pitch of the dots can be from 10 ⁇ m to 10 mm, and the thickness can be from 5 nm to 200 ⁇ m. 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 105 below the bottom insulating layer 101 , 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 105 can pass through the electrode sites in the bottom insulating layer 101 at positions corresponding to the electrode sites.
  • the vias are electrically coupled to corresponding conductors.
  • the electrode sites in the bottom electrode site layer 105 may be located at opposite positions to the electrode sites in the top electrode site layer 104 on both top and bottom sides of the flexible electrode 100 and with Electrode sites in the oppositely located top electrode site layer 104 are electrically coupled to the same conductors in the conductor layer 103 .
  • the electrode sites in the bottom electrode site layer 105 may also be located at different positions on the top and bottom sides of the flexible electrode 100 than the electrode sites in the top electrode site layer 104, so as to Electrical signals are collected or applied in different areas of the biological tissue; and in embodiments according to the present disclosure, the electrode sites in the bottom electrode site layer 105 can also be electrically coupled to the top electrode site layer 104 in the conductor layer 103 The electrode sites in the wires are different.
  • the bottom electrode site layer 105 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 104 but not the bottom electrode site layer 105 .
  • 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 103 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 101 and/or the top insulating layer 102, 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 120 of the flexible electrode 100 may include a back end site in the back end site layer 106 , and the back end site may be electrically coupled to one of the conductors (shown in FIG. 1 ).
  • the backend sites in the backend site layer 106 are electrically coupled to the metal ring at the end of one of the wires) and are electrically coupled to the backend circuitry through a via in at least one of the bottom insulating layer 101 and the top insulating layer 102 , to achieve bidirectional signal transmission between the electrode site electrically coupled to the wire and the back-end circuit.
  • FIG. 1 shows an embodiment according to the present disclosure, as shown in FIG.
  • the back-end site is located between the conductor layer 103 and the bottom insulation layer 101 , and the back-end site passes through the metal ring of the conductor layer 103 and the top insulation layer 102
  • the through hole can be electrically coupled to 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 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 commercial signal recording systems.
  • the connection methods include ball mounting and Anisotropic Conductive Film Bonding (ACF). Bonding) etc.
  • 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 106 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 vary according to design needs.
  • the back-end site in a connected manner may include multiple layers in the thickness direction, and the material of the adhesive layer close to the wire layer 103 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 101 and 102 is an anti-oxidation protective layer.
  • the back-end site layer 106 may be a metal film including three superimposed layers, wherein the first layer close to the conductor layer 103 may be a nanometer-scale adhesive layer to improve the back end.
  • the material of the first layer as the adhesion layer can be Cr, Ta, TaN, Ti or TiN
  • the material of the second layer as the soldering flux layer can be It is nickel (Ni), Pt or palladium (Pd)
  • the third layer as the conductive layer can be Au, Pt, Ir, W, Mg, Mo, platinum-iridium alloy, titanium alloy, graphite, carbon nanotube, PEDOT wait.
  • backend site layer can also be made of other conductive metallic materials or non-metallic materials.
  • the back-end site layer 106 in Figure 1 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 100 and the back-end circuit connected to the back-end portion 120 may be packaged together by any one of epoxy resin and polydimethylsiloxane or a combination thereof to improve its intensity.
  • 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.
  • 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 flexible electrode 100 may further include a flexible separation layer 108 .
  • the flexible separation layer 108 of the flexible electrode 100 in FIG. 1 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 thereto, 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 flexible separation layer can be used to separate the entire electrode or only the flexible part of the electrode from the substrate, separate the flexible substrate from the hard substrate, separate parts that have too strong adhesion and need to be separated, etc.
  • the material of the flexible separation layer may be metallic or non-metallic materials such as Ni, Cr, aluminum (Al).
  • FIG. 4 illustrates an exploded view of at least a portion of a flexible electrode 400 for peripheral nerves in accordance with an embodiment of the present disclosure.
  • the flexible electrode 400 is similar to the flexible electrode 100 described above with reference to FIG. 1, and can be implanted into two completely amputated nerves, and utilizes the active formation of a tight electrode tissue interface with the electrode during the nerve and blood vessel repair process to achieve signal transmission. Record and measure.
  • flexible electrode 400 may include an implant portion 410 that may be implanted into an amputated peripheral nerve or nerve stump and configured to collect or apply electrical signals within and on the surface of the peripheral nerve bundle.
  • the implant part 410 may have pores and be stretchable. The pores and stretchability of the implant part 410 may facilitate the reconstruction of the peripheral nerve into which it is implanted, and make the implant part 410 closely connected to the peripheral nerve after reconstruction. touch.
  • the shape and size of the pores can be designed according to the size of the peripheral nerves, and the porosity of the implanted part 410 is more than 70%.
  • the implant portion 410 may include an outer annular portion 411 and one or more extension portions 412 extending inwardly from the outer annular portion 411 .
  • extension portions 412 symmetrically extend linearly and radially inwardly from the outer annular portion 411 , respectively, to form a sector-shaped gap between the outer annular portion 414 and the extension portion 412 .
  • the shape, number and arrangement of the extension parts are not limited thereto.
  • the extension portions 412 may also be asymmetrical to each other.
  • the outer annular portion 411 can surround the reconstructed peripheral nerve, and the one or more extension portions 412 can extend inside the peripheral nerve and deform as the peripheral nerve is reconstructed.
  • one or more extension portions 412 may be stretched longer due to reconstruction of the peripheral nerve and thus remain in close contact with the peripheral nerve, and the flexible material from which flexible electrode 400 is made may facilitate such deformation.
  • the one or more extension portions 412 may conform to the reconstruction of the peripheral nerve and have a different arrangement than the arrangement in which the flexible electrode 400 was originally manufactured.
  • the one or more extension portions 412 may not be in the same plane. And are not symmetrical to each other, but can extend in different directions or angles from the outer annular portion 411.
  • the two extending portions 412 shown as collinear in the same plane in Figure 4 can form a certain angle.
  • the one or more extensions 412 may be dipped in a biocompatible adhesive such as, but not limited to, low modulus silicone such that the one or more extensions 412 are coated with a biocompatible adhesive. Adhesive for waterproofing.
  • the flexible electrode 400 may further include a rear end portion 420, which may be implanted subcutaneously and may be used to couple the flexible electrode 400 and the rear end circuit to perform rear end transfer, implantation Portion 410 extends from the rear end portion 420 .
  • the flexible electrode 400 shown in Figure 1 includes an implant portion 410 having a circular profile and an elongated rear end portion 420, but it should be understood that Figure 4 shows only a non-limiting example for peripheral nerve bundles.
  • the flexible electrode can have implant portion 410 and rear end portion 420 of different shapes and sizes as needed.
  • the flexible electrode 400 has a multi-layer structure, specifically, including a bottom insulating layer 401 , a top insulating layer 402 , a wire layer 403 , and an electrode site layer 404 , back-end site layer 406, flexible separation layer 408, etc., these layers are the same as the bottom insulating layer 101, the top insulating layer 102, the conductor layer 103, the electrode site layer 104, the back-end described above with respect to the flexible electrode 100 of Figure 1
  • the site layer 106 and the flexible separation layer 108 are similar and will not be described again here.
  • the layers of the flexible electrode 400 shown in FIG. 4 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.
  • FIG. 5 illustrates an enlarged view of at least a portion of a lead and electrode site at an implanted portion of a flexible electrode for peripheral nerves, the view being the implanted portion shown in FIG. 4 , in accordance with an embodiment of the present disclosure.
  • wires 513 extend along at least a portion of the outer annular portion of the implant portion and then extend linearly along the extended portion of the implant portion and are electrically coupled to corresponding electrode sites 514 .
  • the wires 513 may be located in different layers from the electrode sites 514, such that the wires 513 are located in the wire layer 403 as shown in Figure 4, and the electrode sites 514 are located in the top electrode site layer as shown in Figure 4 In 404; the wire 513 can also be located in the same layer as the electrode site 514, that is, the flexible electrode may not include an electrode site layer, and both the wire and the electrode site are located in the wire layer between the top insulating layer and the bottom insulating layer, And the electrode site 514 is exposed to the outer surface of the electrode and in contact with the peripheral nerve through the through hole in at least one of the top insulating layer and the bottom insulating layer.
  • each extension portion may include a plurality of conductive wires 613 extending linearly along it and a corresponding plurality of electrode sites 614 , wherein each electrode site 614 is coupled to its corresponding one conductive wire 613 , and each conductive wire 613 spaced apart from each other and extending linearly parallel to each other.
  • the implant portion shown in Figure 7 includes an inner annular portion 713 in addition to an outer annular portion and one or more extension portions respectively extending inwardly therefrom.
  • one or more extension portions 712 respectively extend radially from the outer annular portion (not shown in FIG. 7 ) to the inner annular portion 713 , narrow where they meet the inner annular portion 713 , and The one or more extension portions 712 may deform or disconnect from the inner annular portion 713 during reconstruction of the peripheral nerve after implantation.
  • the inner annular portion 713 may be disposed with conductive wires and electrode sites.
  • the conductive wires may extend to the inner annular portion 713 along the rear end portion, at least a portion of the outer annular portion, and the extension portion and be electrically coupled. to the electrode site at inner annular portion 713.
  • the inner annular portion 713 may not be arranged with wires and electrode sites, and may only include at least one of a top insulation layer and a bottom insulation layer.
  • the outer diameter of the inner annular portion 713 may be 300 nm to 10 ⁇ m
  • the inner diameter may be 250 nm to 40 ⁇ m
  • the width may be 5 ⁇ m to 40 ⁇ m.
  • FIG. 12 shows a schematic diagram of deformation of an implanted portion of a flexible electrode according to an embodiment of the present disclosure.
  • the implanted part of the flexible electrode will deform, wherein the extension part 1212 extending from the outer annular part 1211 will deform with the reconstruction, For example, being stretched, the inner annular portion 1213 to which extension portion 1212 extends may shift with reconstruction, such as no longer being in the same plane as the remainder of the implanted portion, and may become displaced due to reconstruction of the surrounding nerves.
  • the stress exerted on the implanted part reaches a certain value, the inner annular part 1213 will break away from the flexible electrode and thus separate from the extension part 1212.
  • internal portions of the implanted portion of the flexible electrode may be configured to perform post-implantation reconstruction of peripheral nerves. Capable of deforming or at least partially disconnecting from the implanted portion.
  • the flexible electrode after the flexible electrode is fabricated, the flexible electrode may be separated from the substrate from which it is fabricated (such as by removing its flexible separation layer) and then connected (e.g., welded ) to the back-end circuit.
  • the flexible electrode and the back-end circuit connected to the back-end part may be encapsulated together by any one of epoxy resin and polydimethylsiloxane or a combination thereof to improve its strength .
  • a gap between the back-end part and the package of the back-end circuit is coated with high-viscosity waterproof glue to ensure the waterproofness of the connection between the flexible electrode and the back-end circuit after implantation.
  • Figure 10 shows a schematic diagram of an implantation manner of a flexible electrode 1000 for peripheral nerves according to an embodiment of the present disclosure.
  • the implanted portion 1010 of the flexible electrode 1000 can be placed between the amputated peripheral nerves or at the nerve stump, and the rear end portion 1020 is placed outside the peripheral nerves and can be implanted subcutaneously.
  • Figure 11 shows a schematic diagram of an implantation manner of a flexible electrode 1100 for peripheral nerves according to an embodiment of the present disclosure.
  • the implanted portion 1110 of the flexible electrode 1100 can be placed between the amputated peripheral nerves or at the nerve stump, and the back-end portion 1120 can be packaged with the back-end circuit before implantation, and can be placed during the implantation.
  • the neck of the flexible electrode between the implanted part and the rear end part can also be coated with a biocompatible adhesive (such as but not limited to silicone), which neck is also located in the body after the flexible electrode is implanted. , so its biocompatibility needs to be improved.
  • a biocompatible adhesive such as but not limited to silicone
  • the implantation of the flexible electrode may include the following steps: inserting the amputated peripheral nerves into a catheter set for auxiliary implantation, and fixing the catheter set to the peripheral nerves using surgical wires for the nerves ; Lay the flexible electrode between the cross-sections of the two sections of the catheter kit, and make the electrode site of the implanted part of the flexible electrode located in the hollow part of the catheter kit to ensure that the electrode site is in contact with the peripheral nerves after implantation; The portions of the implant portion that are in contact with the catheter set, such as the outer annular portion, are coated with a biocompatible adhesive for protection and fixation.
  • the implantation of the flexible electrode may also include welding the rear end portion of the flexible electrode to the rear end circuit, encapsulating the rear end portion and the rear end circuit together, and coating the rear end portion and the rear end circuit with high-viscosity waterproof glue.
  • the catheter set for assisting implantation may be a Cuff electrode, and electrode sites are arranged on the inner side of the Cuff electrode.
  • a plurality of parallel wire rings may be fixed on the inner side of the Cuff electrode.
  • the Cuff electrode can be configured to open and close on the surface of the peripheral nerve, so that the flexible electrode can be used to record the action potential signal of a single nerve fiber within the nerve bundle, while the Cuff electrode can be used to record the action potential signal outside the nerve bundle. local field potential signal.
  • the catheter set used for assisted implantation may also be a silicone tube with good flexibility and elasticity, etc.
  • FIG. 8 shows a flowchart of a method 800 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 800 may include: at S81 , manufacturing a first insulating layer, a conductor layer and a second insulating layer on the substrate, wherein the first insulating layer and the second insulating layer are formed by patterning. Through-holes are made in at least one layer at positions corresponding to the electrode sites; and at S82 , the flexible electrode is separated from the substrate.
  • the steps of manufacturing each layer of the flexible electrode at S81 are described in detail below with reference to FIG. 9 .
  • Figure 9 shows a schematic diagram of a method 900 of manufacturing a flexible electrode according to an embodiment of the present disclosure.
  • 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. 9 .
  • View (A) of Figure 9 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 9 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 9 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 9 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 9 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 lithography, in which the mask and the structure are exposed in a vacuum contact mode. 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 9 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.
  • 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 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 part of the top insulating layer can be removed by oxygen plasma etching, and then the remaining photoresist on the top insulating layer can be removed with a developer or acetone after flood exposure to obtain the structure shown in view (K) .
  • the top insulating layer may also undergo an adhesion-promoting treatment before manufacturing to improve the bonding force between the bottom insulating layer and the top insulating layer.
  • View (L) of Figure 9 shows the fabrication of the top electrode site layer over the top insulating layer.
  • the manufacturing method 900 shown in FIG. 9 is suitable for the case where each part of the flexible electrode has the same thickness of each layer.
  • the flexible electrode may have different thicknesses between portions, such that at least one of the first insulating layer and the second insulating layer of the outer annular portion in the implanted portion may be thickened .
  • Figure 13 shows a schematic diagram of a method 1300 for fabricating flexible electrodes for peripheral nerves in accordance with an embodiment of the present disclosure.
  • the manufacturing method 1300 shown in FIG. 13 is suitable for the case where the top insulation layer of the outer annular portion is thickened.
  • Views (A) to (G) of FIG. 13 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. 9 and will not be described again.
  • Views (H) to (K) of Figure 13 illustrate the fabrication of the top insulating layer.
  • FIG. 13 shows the structure obtained after the top insulating layer is formed.
  • View (I) of FIG. 13 shows the application of photoresist and mask on top of the filmed top insulating layer, wherein the pattern of the mask is set to be related to the top insulating layer.
  • FIG. 13 shows the application of photoresist and mask on top of the filmed top insulating layer, wherein the pattern of the mask is set to be related to the top insulating layer.
  • View (J) of FIG. 13 shows a structure including an etching resist layer obtained after exposure and development.
  • View (K) of FIG. 13 shows the structure of the top insulating layer after etching. At this time, the thickness of the top insulating layer of the outer annular portion, the extension portion, the inner annular portion, etc. is the same.
  • View (L) of Figure 13 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 outer annular portion Insulation layer related, for example, the pattern of the top insulating layer 102 of the outer annular portion shown in Figure 1 can be achieved.
  • View (M) of FIG. 13 shows a structure including an etching-resistant layer obtained after re-exposure and development. The etching-resistant layer is located on the insulating layer of the outer annular portion to protect the insulating layer of the outer annular portion, and Expose the insulation of extensions and inner ring sections, etc.
  • View (N) of FIG. 13 shows the final top insulating layer obtained after etching, in which a portion of the insulating layer of the extension portion, the inner annular portion, etc. is etched away, so that its thickness is smaller than that of the outer annular portion.
  • View (O) of FIG. 13 shows the fabrication of a top electrode site layer by evaporation or the like on the top insulating layer.
  • the present disclosure provides a flexible electrode for peripheral nerves and a method of manufacturing the same.
  • This flexible electrode uses flexible materials to replace hard silicon-based electrodes, uses polymers as an insulating layer to wrap conductive materials, and reduces the thickness of the electrode to reduce its bending stiffness, thereby improving the mechanical properties between the electrode and tissue. mismatch problem, ultimately providing a long-term stable electrical signal recording and stimulation interface.
  • the flexible electrode adopts a porous design, and uses the characteristics of peripheral nerves to be rebuilt to implant the electrodes into the completely amputated nerves at both ends. During the nerve and blood vessel repair process, it actively forms a tight electrode tissue interface with the electrode to achieve signal transmission. Record and stimulate.
  • 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周围神经的柔性电极及其制造方法。提供了一种用于周围神经的柔性电极，所述柔性电极包括可植入到截断的周围神经或神经残端并且被配置为在周围神经束内部和表面采集或施加电信号的植入部分，其中：所述柔性电极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；所述植入部分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周围神经接触，以从周围神经采集电信号并通过导线传输采集到的电信号，或向周围神经施加通过导线接收到的电信号；以及所述植入部分具有孔隙，以便于周围神经的重建并在重建后与周围神经紧密接触。

Description

一种用于周围神经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202210689969.9，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周围神经的柔性电极及其制造方法。
背景技术
在中国大约有两千四百万人正在遭受不同程度的四肢残疾，四肢残疾的产生原因有身体创伤、神经退行性疾病、以及截肢等。身体不便对这些残疾人士的日常生活产生了巨大的影响。神经电极可用于控制断肢的周围神经。
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，提供了一种用于周围神经的柔性电极，所述柔性电极包括可植入到截断的周围神经或神经残端并且被配置为在周围神经束内部和表面采集或施加电信号的植入部分，其中：所述柔性电极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；所述植入部分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周围神经接触，以从周围神经采集电信号并通过导线传输采集到的电信号，或向周围神经施加通过导线接收到的电信号；以及所述植入部分具有孔隙，以便于周围神经的重建并在重建后与周围神经紧密接触。
根据本公开的第二方面，提供了一种用于周围神经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周围神经的柔性电极的至少一部分的分解图；
图2示出了根据本公开的实施例的用于周围神经的柔性电极的植入部分处的导线及电极位点的至少一部分的放大视图；
图3示出了根据本公开的实施例的用于周围神经的柔性电极的植入部分处的一个延伸部分的导线及电极位点的至少一部分的放大视图；
图4示出了根据本公开的实施例的用于周围神经的柔性电极的至少一部分的分解图；
图5示出了根据本公开的实施例的用于周围神经的柔性电极的植入部分处的导线及电极位点的至少一部分的放大视图；
图6示出了根据本公开的实施例的用于周围神经的柔性电极的植入部分的延伸部分的导线及电极位点的至少一部分的放大视图；
图7示出了根据本公开的实施例的用于周围神经的柔性电极的植入部分的延伸部分和内部环形部分的放大视图；
图8示出了根据本公开的实施例的制造用于周围神经的柔性电极的方法的流程图；
图9示出了根据本公开的实施例的制造用于周围神经的柔性电极的方法的示意图；
图10示出了根据本公开的实施例的用于周围神经的柔性电极的植入方式的示意图；
图11示出了根据本公开的实施例的用于周围神经的柔性电极的植入方式的示意 图；
图12示出了根据本公开的实施例的柔性电极的植入部分发生形变的示意图；
图13示出了根据本公开的实施例的用于制造用于周围神经的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。
束外神经电极在应用时通常包裹在外周神经束的外侧，通常位点数量小于10，只可记录局部场电位信号，并且由于存在免疫疤痕导致无法长期稳定记录和刺激。束外神经电极包括Cuff电极、FINE电极以及柔性的Helical电极等。在使用时，束外神经电极被组装在硅胶软管或扁平导管内壁上，然后将硅胶软管或扁平导管包裹在神经束的外侧。因此，在使用时，束外神经电极的包裹在神经外侧的硅胶软管可能与神经束发生相对位移；并且在长期使用过程中，硬质的导管和神经束之间的摩擦会造成神经的损伤，神经上形成的瘢痕会影响信号的记录和刺激；束外神经电极只能记录到复合动作电位信号，并进行大范围的神经刺激，记录和刺激精度远不能满足精细控制的需求；另外，电极记录到的分辨率也较低。
束内神经电极通常将电极记录端排布在长条形基底上并将基底插入神经束中的电极。常用的束内神经电极包括硬质的Utah电极、Floating电极和Michigan电极等。束内电极植入于外周神经束内，可以同时记录动作电位与局部场电位信号，但硬质电极会引起较大组织损伤，导致电极周围胶质细胞的局部聚集，而且硬质电极尖端比较脆，容易脱落和折断，导致无法长期稳定记录和刺激。
目前相关技术的瓶颈是如何提供长期稳定多通道数的控制信号，具体而言，需要实现直接控制断肢的外周神经有潜质输出高通量的精细控制信号，并接收包括温度、压力、痛觉在内的复杂感知信号。因此亟需一款高通道数、高选择性、超柔性、能够进行长期稳定记录和刺激的外周神经电极。
图1示出了根据本公开的实施例的用于周围神经的柔性电极100的至少一部分的分解图。该柔性电极100利用周围神经能够重建的特性，可以被植入到完全截断的两段神经中，利用神经和血管修复过程中主动与电极形成紧密的电极组织界面来实现信号的记录和测量，具有优于如上所述的束内神经电极和束外神经电极的性能。
如图1所示，柔性电极100可以包括植入部分110，该植入部分110可植入到截断的周围神经或神经残端并且被配置为在周围神经束内部和表面采集或施加电信号。植入部分110可以具有孔隙并且可拉伸。植入部分110的孔隙和可拉伸性可以便于其所植入到的周围神经的重建，并在重建后使得该植入部分110与周围神经紧密接触。孔隙的形状和尺寸可以根据周围神经的尺寸设计，并且植入部分110的孔隙率为70％以上。在根据本公开的实施例中，植入部分110可以包括外部环形部分111和从该外部环形部分111向内延伸的一个或多个延伸部分112。在图1中示出的实施例中，六个延伸部分112对称地分别从外部环形部分111蛇形地向内延伸并且彼此平行，以在外部环形部分111和一个或多个延伸部分112之间形成孔隙，但应理解的是，延伸部分的形状、数量和布置不限于此。例如，图4示出的柔性电极400中，延伸部分412线性地向内延伸，该实施例将在下文详述。在根据本公开的实施例中，柔性电极100中，这些延伸部分112也可以是彼此不对称或不平行的。在植入后，外部环形部分111可以围绕重建后的周围神经，一个或多个延伸部分112可以从外部环形部分111向周围神经内部延伸并随着周围神经的重建而发生形变。例如，此时，一个或多个延伸部分112可以由于周围神经的重建而被拉伸得更长并因此保持与周围神经的紧密接触，延伸部分112的蛇形结构及制成柔性电极100的柔性材料可以有利于这种形变。并且，此时，一个或多个延伸部分112可以顺应于周围神经的重建而具有与柔性电极100被 初始制造成的布置不同的布置，例如，一个或多个延伸部分112可以不处于同一平面中并且彼此不平行，而是可以从外部环形部分111以不同方向或角度延伸，例如，图1中示出为同一平面中共线的两个延伸部分112可以形成一定角度。在柔性电极100制成之后进行与后端电路的连接或封装时，可以将一个或多个延伸部分112浸渍在生物兼容性黏附剂(诸如但不限于低模量硅酮)中以使得该一个或多个延伸部分112涂有生物兼容性黏附剂，起到防水作用。
在图1和图4所示的柔性电极中，延伸部分被示出为线性或蛇形，但应理解的是，根据本公开的柔性电极不限于此，延伸部分还可以采取马蹄形、轮状、带状、条状、网状等形状。
在根据本公开的实施例中，柔性电极100还可以包括后端部分120，该后端部分120可植入于皮下，可用于接合柔性电极100和后端电路以进行后端转接，植入部分110从该后端部分120延伸。图1中示出的柔性电极100包括具有圆形轮廓的植入部分110和细长的后端部分120，但应理解的是，图1示出的仅仅是非限制性示例，用于周围神经束的柔性电极可以根据需要，具有不同形状和尺寸的植入部分110以及后端部分120。
从图1可以清楚地看出，柔性电极100为多层结构，具体而言，包括底部绝缘层101、顶部绝缘层102、导线层103、电极位点层104、后端位点层106、柔性分离层108等。应理解的是，图1中示出的柔性电极100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100可以包括位于底部的绝缘层101和位于顶部的绝缘层102。具体而言，如图1所示，柔性电极100的植入部分110和后端部分120可以均包括绝缘层101、102。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101、102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101、102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101、102还是柔性电极100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101、102的厚度可以为100nm至300μm。
在根据本公开的实施例中，柔性电极100的外部环形部分111可以与其他部分(诸如，延伸部分112等)相比加厚，以提供更高的强度。例如，外部环形部分111处的底部绝缘层101和顶部绝缘层102中的至少一层可以加厚。
柔性电极100还可以包括在底部绝缘层101和顶部绝缘层102之间的导线层103中的导线。具体而言，如图1所示，柔性电极100的植入部分110和后端部分120可以均包括导线层103。在根据本公开的实施例中，这些导线沿着后端部分120延伸至植入部分120，并且在植入部分120中沿着外部环形部分111的至少一部分以及延伸部分112之一延伸至位于延伸部分112的电极位点。在根据本公开的实施例中，柔性电极100可以包括同一导线层103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104中的电极位点并且电耦合到后端位点层106中的后端位点。各导线可以具有微米级的宽度和纳米级的厚度。在本公开的实施例中，导线层103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103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103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101和102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。
柔性电极100还可以包括位于顶部绝缘层102之上的顶部电极位点层104中的电极位点，每个电极位点电耦合到导线层103中的导线之一，并且在柔性电极100的植入后与周围神经接触，以从周围神经采集电信号并通过导线传输采集到的电信号，或 向周围神经施加通过导线接收到的电信号。
在图1中示出的柔性电极100中，植入部分110中的六个延伸部分112中的每一个均包括多个相应的电极位点，其中，距离外部环形部分111较近的电极位点可用于在周围神经表面施加或采集信号，距离外部环形部分111较远的电极位点可用于在周围神经内部施加或采集信号。但应理解的是，本公开不限于此，柔性电极的每个延伸部分可以根据需要包括用于在周围神经内部和表面施加或采集信号的一个多个电极位点。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100用作刺激电极时，其中每个电极位点可以同步或异步地在周围神经表面的深部和/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100用作记录电极时，这些电极位点可以同时精细地采集周围神经表面的深部和/或表面的不同位置处的电信号。
图2示出了根据本公开的实施例的用于周围神经的柔性电极的植入部分处的导线及电极位点的至少一部分的放大视图，该视图是如图1中所示的植入部分110的导线及电极位点的至少一部分的放大视图。如图2所示，导线213沿着植入部分的外部环形部分的至少一部分延伸，然后沿着植入部分的延伸部分蛇形延伸，并电耦合到相应的电极位点214。这里，导线213可以与电极位点214位于不同层中，诸如，导线213位于如图1中所示的导线层103中，并且电极位点214位于如图1中所示的顶部电极位点层104中；导线213也可以与电极位点214位于同一层中，即，柔性电极可以不包括电极位点层，导线和电极位点均位于顶部绝缘层和底部绝缘层之间的导线层中，并且电极位点214通过顶部绝缘层和底部绝缘层中的至少一层中的通孔而暴露于电极的外表面并与周围神经接触。
图3示出了根据本公开的实施例的用于周围神经的柔性电极的植入部分处的一个延伸部分的导线及电极位点的至少一部分的放大视图，该视图是如图1中所示的六个延伸部分112之一中的导线及电极位点的至少一部分的放大视图。如图3所示，每个延伸部分可以包括沿其蛇形延伸的多个导线313以及相应的多个电极位点314，其中每个电极位点314耦合到其对应的一个导线313，各导线313彼此间隔开一定距离并以彼此平行的方式蛇形延伸。
返回参考图1，在柔性电极100中，顶部电极位点层104中的电极位点可以通过顶部绝缘层102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104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102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104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103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104可以是包括叠加的两个分层的金属薄膜，其中，接近导线层103的第一分层为Ti、TiN、Cr、Ta或TaN，电极位点层104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，最大边长或直径可以为1μm至500μm，各电极位点的间距可以为10μm至10mm，厚度可以为5nm至200μm。应理解的是，电极位点的形状、数量、尺寸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1中未示出，但柔性电极还可以包括位于底部绝缘层101之下的底部电极位点层105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104中的电极位点类似地，在柔性电极100中，底部电极位点层105中的电极位点可以通过底部绝缘层101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105中的电极位点可以与顶部电极位点层104中的电极位点位于柔性电极100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104中的电极位点电耦合到导线层103中的同一导线。在根据本公开的实施例中，底部电极位点层105中的电极位点也可以与顶部电极位点层104中的电极位点位于柔性电极100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105中的电极位点也可以电耦合到导线层103中的与顶部电极位点层104中的电极位点不同的导线。
应理解的是，底部电极位点层105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104而不包括底部电极位点层105。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103，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101和/或顶部绝缘层102，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100的后端部分120可以包括后端位点层106中的后端位点，后端位点可以通过电耦合到导线之一(图1中示出为后端位点层106中的后端位点电耦合到导线之一末端的金属圈)并通过底部绝缘层101和顶部绝缘层102中的至少一层中的通孔电耦合到后端电路，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。在根据本公开的实施例中，如图1所示，后端位点位于导线层103与底部绝缘层101之间，并且后端位点通过导线层103的金属圈以及顶部绝缘层102中的通孔而可电耦合到后端电路，这种布置不将后端位点置于柔性电极100的外表面，从而有利于柔性电极100与后端电路的稳固连接。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。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，连接方式包括植球贴片以及异方性导电胶膜键合(Anisotropic Conductive Film Bonding，ACF Bonding)等。
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106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。
以连接方式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103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101、102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106可以是包括叠加的三个分层的金属薄膜，其中，接近导线层103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106与导线层103之间的粘附，作为粘附分层的第一分层的材料可以为Cr、Ta、TaN、Ti或TiN，作为助焊分层的第二分层可以为镍(Ni)、Pt或钯(Pd)，作为导电分层的第三分层可以为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1中的后端位点层106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100和与后端部分120连接的后端电路可以由环氧树脂和聚二甲基硅氧烷中的任一种或其组合封装在一起，以提高其强度。
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。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。
在根据本公开的实施例中，柔性电极100还可以包括柔性分离层108。图1中的柔性电极100的柔性分离层108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。具体而言，柔性分离层可以用于将整个电极或仅将电极的柔性部分与衬底分离、将柔性衬底与硬质衬底分离、分离粘合力过强而又需要分离的部分等。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。
图4示出了根据本公开的实施例的用于周围神经的柔性电极400的至少一部分的分解图。该柔性电极400与前文参考图1所述的柔性电极100类似，可以被植入到完全截断的两段神经中，利用神经和血管修复过程中主动与电极形成紧密的电极组织界面来实现信号的记录和测量。
如图4所示，柔性电极400可以包括植入部分410，该植入部分410可植入到截断的周围神经或神经残端并且被配置为在周围神经束内部和表面采集或施加电信号。植入部分410可以具有孔隙并且可拉伸，植入部分410的孔隙和可拉伸性可以便于其所植入到的周围神经的重建，并在重建后使得该植入部分410与周围神经紧密接触。孔隙的形状和尺寸可以根据周围神经的尺寸设计，并且植入部分410的孔隙率为70％以上。在根据本公开的实施例中，植入部分410可以包括外部环形部分411和从该外部环形部分411向内延伸的一个或多个延伸部分412。在图4中示出的实施例中，六个延伸部分412对称地分别从外部环形部分411线性地径向向内延伸，以在外部环形部分414和延伸部分412之间形成扇形的孔隙。但应理解的是，延伸部分的形状、数量和布置不限于此。柔性电极400中，延伸部分412也可以是彼此不对称的。在植入后，外部环形部分411可以围绕重建后的周围神经，一个或多个延伸部分412可以在周围神经内部延伸并随着周围神经的重建而发生形变。例如，此时，一个或多个延伸部分412可以由于周围神经的重建而被拉伸得更长并因此保持与周围神经的紧密接触，制成柔性电极400的柔性材料可以有利于这种形变。并且，此时，一个或多个延伸部分412可以顺应于周围神经的重建而具有与柔性电极400被初始制造成的布置不同的布置，例如，一个或多个延伸部分412可以不处于同一平面中并且彼此不对称，而是可以从外部环形部分411以不同方向或角度延伸，例如，图4中示出为同一平面中共线的两个延伸部分412可以形成一定角度。在柔性电极400制成之后，可以将一个或多个延伸部分412浸渍在生物兼容性黏附剂(诸如但不限于低模量硅酮)中以使得该一个或多个延伸部分412涂有生物兼容性黏附剂以起到防水作用。
在根据本公开的实施例中，柔性电极400还可以包括后端部分420，该后端部分420可植入于皮下，可用于接合柔性电极400和后端电路以进行后端转接，植入部分410从该后端部分420延伸。图1中示出的柔性电极400包括具有圆形轮廓的植入部分410和细长的后端部分420，但应理解的是，图4示出的仅仅是非限制性示例，用于周围神经束的柔性电极可以根据需要，具有不同形状和尺寸的植入部分410以及后 端部分420。
类似于图1中示出的柔性电极100，可以清楚地看出，柔性电极400为多层结构，具体而言，包括底部绝缘层401、顶部绝缘层402、导线层403、电极位点层404、后端位点层406、柔性分离层408等，这些层与前文关于图1的柔性电极100所描述的底部绝缘层101、顶部绝缘层102、导线层103、电极位点层104、后端位点层106、柔性分离层108类似，在此不再赘述。应理解的是，图4中示出的柔性电极400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。
图5示出了根据本公开的实施例的用于周围神经的柔性电极的植入部分处的导线及电极位点的至少一部分的放大视图，该视图是如图4中所示的植入部分410的导线及电极位点的至少一部分的放大视图。如图5所示，导线513沿着植入部分的外部环形部分的至少一部分延伸，然后沿着植入部分的延伸部分线性延伸，并电耦合到相应的电极位点514。这里，导线513可以与电极位点514位于不同层中，诸如，导线513位于如图4中所示的导线层403中，并且电极位点514位于如图4中所示的顶部电极位点层404中；导线513也可以与电极位点514位于同一层中，即，柔性电极可以不包括电极位点层，导线和电极位点均位于顶部绝缘层和底部绝缘层之间的导线层中，并且电极位点514通过顶部绝缘层和底部绝缘层中的至少一层中的通孔而暴露于电极的外表面并与周围神经接触。
图6示出了根据本公开的实施例的用于周围神经的柔性电极的植入部分的延伸部分的导线及电极位点的至少一部分的放大视图，该视图是如图4中所示的六个延伸部分412之一中的导线及电极位点的至少一部分的放大视图。如图6所示，每个延伸部分可以包括沿其线性延伸的多个导线613以及相应的多个电极位点614，其中每个电极位点614耦合到其对应的一个导线613，各导线613彼此间隔开一定距离并以彼此平行的方式线性延伸。
图7示出了根据本公开的实施例的用于周围神经的柔性电极的植入部分的延伸部分和内部环形部分的放大视图，该视图示出了图4中所示的柔性电极400的优选实施例的至少一部分，图7中示出的植入部分除了外部环形部分和从外部环形部分分别向内延伸的一个或多个延伸部分之外还包括内部环形部分713。如图7所示，一个或多个延伸部分712分别从外部环形部分(图7中未示出)径向延伸到内部环形部分713，在与内部环形部分713相接的位置变窄，并且在植入后周围神经的重建过程中该一个 或多个延伸部分712可从内部环形部分713变形或断开。具有这种内部环形部分的结构能够进一步提供周围神经的重建空间。在根据本公开的实施例中，该内部环形部分713可以布置有导线及电极位点，例如，导线可以沿后端部分、外部环形部分的至少一部分以及延伸部分延伸至内部环形部分713并电耦合到内部环形部分713处的电极位点。在根据本公开的实施例中，该内部环形部分713也可以不布置有导线及电极位点，仅包括顶部绝缘层和底部绝缘层中的至少一层。作为非限制性示例，在图7所示的结构中，内部环形部分713的外径可以为300nm至10μm，内径可以为250nm至40μm，宽度可以为5μm至40μm。
图12示出了根据本公开的实施例的柔性电极的植入部分发生形变的示意图。如图12所示，在柔性电极植入后的周围神经的重建过程中，柔性电极的植入部分会发生形变，其中，从外部环形部分1211延伸的延伸部分1212会随着重建而发生形变，诸如，被拉伸，延伸部分1212延伸到的内部环形部分1213会随着重建而发生移位，诸如，不再和植入部分的其余部分位于同一平面中，并且，在由于周围神经的重建而施加在植入部分上的应力达到一定数值时，内部环形部分1213会从柔性电极断开，从而与延伸部分1212分离。
在根据本公开的实施例中，柔性电极的植入部分的内部部分(诸如但不限于前文所述的延伸部分和/或内部环形部分)可以被配置为在植入后周围神经的重建过程中能够发生形变或至少部分地从植入部分断开。
在根据本公开的实施例中，在柔性电极制成后，可以将柔性电极从其制造的基底分离(诸如，通过去除其柔性分离层而从基底分离)，然后将柔性电极连接(例如，焊接)到后端电路。在根据本公开的实施例中，柔性电极和与后端部分连接的后端电路可以由环氧树脂和聚二甲基硅氧烷中的任一种或其组合封装在一起，以提高其强度。在根据本公开的实施例中，后端部分与后端电路的封装的间隙涂抹有高粘性防水胶，以保证在植入后柔性电极和后端电路之间的连接的防水性。
图10示出了根据本公开的实施例的用于周围神经的柔性电极1000的植入方式的示意图。如图10所示，柔性电极1000的植入部分1010可以被置于截断的周围神经之间或置于或神经残端，后端部分1020置于周围神经之外，并且可以植入于皮下。图11示出了根据本公开的实施例的用于周围神经的柔性电极1100的植入方式的示意图。如图11所示，柔性电极1100的植入部分1110可以被置于截断的周围神经之间或置于神经残端，后端部分1120在植入之前可以与后端电路封装在一起，并在植入时置 于周围神经之外并且植入于皮下。在植入时，柔性电极的在植入部分和后端部分之间的颈部还可以涂抹有生物兼容性黏附剂(诸如但不限于硅胶)，该颈部在植入柔性电极后也位于体内，因此需提高其生物兼容性。
在根据本公开的实施例中，柔性电极的植入可以包括如下步骤：将截断的周围神经分别套入用于辅助植入的导管套件，并利用神经用外科手术线将导管套件固定到周围神经；将柔性电极平铺在两段导管套件的截面之间，并使得该柔性电极的植入部分的电极位点位于导管套件的中空部分中，以保证植入后电极位点与周围神经接触；利用生物兼容性黏附剂涂抹植入部分的与导管套件接触的部分(诸如，外部环形部分)，以进行保护和固定。此外，柔性电极的植入还可以包括诸如将柔性电极的后端部分焊接到后端电路、将后端部分与后端电路封装在一起、利用高粘性防水胶涂抹后端部分与后端电路的封装的间隙、利用生物兼容性黏附剂涂抹柔性电极的颈部等等步骤中的一个或多个。
在根据本公开的实施例中，用于辅助植入的导管套件可以是Cuff电极，Cuff电极的内侧布置有电极位点，诸如，Cuff电极的内侧可以固定有多个平行的金属丝环。在植入柔性电极时，Cuff电极可以被配置为开合套在周围神经的表面上，从而能够在利用柔性电极记录神经束内单个神经纤维的动作电位信号的同时利用Cuff电极记录神经束外的局部场电位信号。在根据本公开的实施例中，用于辅助植入的导管套件也可以是具有良好的柔性和弹性的硅胶管等。
图8示出了根据本公开的实施例的制造柔性电极的方法800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8所示，方法800可以包括：在S81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S82处，从基底分离出柔性电极。以下结合图9详述S81处制造柔性电极的各层的步骤。
图9示出了根据本公开的实施例的制造柔性电极的方法900的示意图。结合图9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9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9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9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9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9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，可以实现前文所述的导线层的图案，诸如，图1的导线层103和图4的导线层403的图案。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，将掩模版与结构在真空接触模式下曝光。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9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1中所示的顶部绝缘层102的图案，即，植入部分110(特别是植入部分110包括的孔隙)和后端部分120的柔性电极100的轮廓以及在顶部绝缘层中的与电极位点和后端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，进行泛曝光后用显影液或丙酮等去除顶 部绝缘层之上剩余的光刻胶，以得到视图(K)中所示的结构。
在根据本公开的实施例中，顶部绝缘层在制造之前还可以进行增粘处理，以提高底部绝缘层和顶部绝缘层之间的结合力。
图9的视图(L)示出了在顶部绝缘层之上制造顶部电极位点层。
图9示出的制造方法900适用于柔性电极的各部分之间具有相同的各层厚度的情况。在根据本公开的实施例中，柔性电极的各部分之间可以具有不同的厚度，诸如，植入部分中的外部环形部分的第一绝缘层和第二绝缘层中的至少一层可以加厚。
图13示出了根据本公开的实施例的用于制造用于周围神经的柔性电极的方法1300的示意图。图13所示的制造方法1300适用于外部环形部分的顶部绝缘层加厚的情况。
图13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9的视图(A)至视图(G)，在此不再赘述。
图13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。为了使得植入部分中的外部环形部分具有与延伸部分和内部环形部分等不同的厚度，这里将外部环形部分的顶部绝缘层制造得更厚。图13的视图(H)示出了顶部绝缘层成膜后得到的结构。图13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1中所示的顶部绝缘层102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13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13的视图(K)示出了刻蚀后的顶部绝缘层的结构，此时，外部环形部分与延伸部分和内部环形部分等的顶部绝缘层的厚度相同。图13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外部环形部分的顶部绝缘层相关，例如，可以实现图1中所示的外部环形部分的顶部绝缘层102的图案。图13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，该抗刻蚀层位于外部环形部分的绝缘层之上，以保护外部环形部分的绝缘层，并暴露延伸部分和内部环形部分等的绝缘层。图13的视图(N)示出了刻蚀之后得到的最终的顶部绝缘层，其中，延伸部分和内部环形部分等的绝缘层被刻蚀掉一部分，因此其厚度小于外部环形部分的绝缘层。
图13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。
本公开提供了一种用于周围神经的柔性电极及其制造方法。该柔性电极采取柔性材料来替代硬质硅基电极，使用高分子聚合物作为绝缘层包裹导电材料，并且降低电极的厚度，以减小其弯曲刚度，从而能够改善电极和组织之间的机械性能不匹配问题，最终提供长期稳定的电信号记录和刺激界面。并且，该柔性电极采用具有孔隙的设计，利用周围神经能够重建的特性将电极植入完全截断的两端神经中，利用神经和血管修复过程中主动与电极形成紧密的电极组织界面来实现信号的记录和刺激。
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 (37)

  1. 一种用于周围神经的柔性电极，所述柔性电极包括可植入到截断的周围神经或神经残端并且被配置为在周围神经束内部和表面采集或施加电信号的植入部分，其中：
    所述柔性电极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；
    所述植入部分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周围神经接触，以从周围神经采集电信号并通过导线传输采集到的电信号，或向周围神经施加通过导线接收到的电信号；以及
    所述植入部分具有孔隙，以便于周围神经的重建并在重建后与周围神经紧密接触。
  2. 根据权利要求1所述的柔性电极，其中，所述植入部分包括外部环形部分以及从所述外部环形部分分别向内延伸的一个或多个延伸部分，所述一个或多个电极位点位于所述一个或多个延伸部分，所述导线层中的导线沿着所述外部环形部分的至少一部分以及所述一个或多个延伸部分中的一个延伸部分延伸到对应的电极位点。
  3. 根据权利要求2所述的柔性电极，其中，所述一个或多个延伸部分分别线性向内延伸。
  4. 根据权利要求3所述的柔性电极，其中，所述植入部分的内部部分被配置为在植入后周围神经的重建过程中能够发生形变或至少部分地从所述植入部分断开。
  5. 根据权利要求2所述的柔性电极，其中，所述一个或多个延伸部分在封装时涂有生物兼容性黏附剂。
  6. 根据权利要求2所述的柔性电极，其中，所述植入部分的所述外部环形部分加厚。
  7. 根据权利要求2所述的柔性电极，其中，所述延伸部分具有蛇形、马蹄形、轮状、带状、条状或网状的形状。
  8. 根据权利要求1至7中任一项所述的柔性电极，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。
  9. 根据权利要求1至7中任一项所述的柔性电极，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，并通过所述至少一层中的通孔电耦合到导线层中的导线。
  10. 根据权利要求9所述的柔性电极，其中，所述电极位点的材料为金、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。
  11. 根据权利要求9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。
  12. 根据权利要求11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，所述粘附分层采取可增强电极位点与导线层的粘附的材料。
  13. 根据权利要求9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。
  14. 根据权利要求1至7中任一项所述的柔性电极，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，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10微米至10毫米，厚度为5纳米至200微米。
  15. 根据权利要求1至7中任一项所述的柔性电极，还包括后端部分，所述后端部分植入于皮下，其中：
    所述植入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。
  16. 根据权利要求15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暴露。
  17. 根据权利要求15所述的柔性电极，其中，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，并电耦合到导线层中的导线。
  18. 根据权利要求17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。
  19. 根据权利要求17所述的柔性电极，其中，后端位点的厚度为5纳米至200微米。
  20. 根据权利要求17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、氮化钛中的任一种或其组合。
  21. 根据权利要求14所述的柔性电极，其中，在将所述柔性电极从基底分离后，所述后端部分连接到后端电路，并且所述后端部分和所述后端电路由环氧树脂和聚二甲基硅氧烷中的任一种或其组合封装在一起。
  22. 根据权利要求21所述的柔性电极，其中，所述后端部分与所述后端电路的封装的间隙涂抹有高粘性防水胶。
  23. 根据权利要求21所述的柔性电极，其中，所述柔性电极的在所述植入部分和所述后端部分之间的颈部涂抹有生物兼容性黏附剂。
  24. 根据权利要求1至7中任一项所述的柔性电极，其中，在植入所述柔性电极时，所述植入部分与用于辅助植入的导管套件的接触部分涂抹有生物兼容性黏附剂，其中在植入所述柔性电极时所述导管套件固定到截断的周围神经并且所述植入部分位于所述导管套件的截面之间。
  25. 根据权利要求24所述的柔性电极，其中，用于辅助植入的导管套件为Cuff电极，所述Cuff电极的内侧布置有电极位点，在植入所述柔性电极时，所述Cuff电极被配置为开合套在周围神经的表面上，从而能够在利用所述柔性电极记录神经束内单个神经纤维的动作电位信号的同时利用所述Cuff电极记录神经束外的局部场电位信号。
  26. 根据权利要求24所述的柔性电极，其中，用于辅助植入的导管套件为具有柔性和弹性的硅胶管。
  27. 根据权利要求1至7中任一项所述的柔性电极，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。
  28. 根据权利要求27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。
  29. 根据权利要求15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、氮化钛中的任一种或其组合。
  30. 根据权利要求1至7中任一项所述的柔性电极，其中，第一绝缘层和第二绝缘层的厚度为100纳米至300微米。
  31. 根据权利要求1至7中任一项所述的柔性电极，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。
  32. 根据权利要求1至7中任一项所述的柔性电极，还包括柔性分离层，其中，所述柔性分离层可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。
  33. 根据权利要求32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。
  34. 根据权利要求32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、钽或钛。
  35. 根据权利要求1至7中任一项所述的柔性电极，其中，所述孔隙的形状和尺寸根据周围神经的尺寸设计，并且所述植入部分的孔隙率为70％以上。
  36. 根据权利要求1至7中任一项所述的柔性电极，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。
  37. 一种用于周围神经的柔性电极的制造方法，所述柔性电极为如权利要求1至36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。
PCT/CN2022/102335 2022-06-17 2022-06-29 一种用于周围神经的柔性电极及其制造方法 WO2023240693A1 (zh)

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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060173263A1 (en) * 2003-02-04 2006-08-03 Jiping He Neural interface assembly and method for making and implanting the same
CN1911470A (zh) * 2006-07-28 2007-02-14 中国科学院上海微系统与信息技术研究所 一种集成药剂释放功能的植入式微电极、制作方法及应用
JP2009285154A (ja) * 2008-05-29 2009-12-10 Nippon Telegr & Teleph Corp <Ntt> 末梢神経型柔軟神経電極およびその作製方法
WO2012139124A1 (en) * 2011-04-07 2012-10-11 Georgia Tech Research Corporation Regenerative microchannel electrode array for peripheral nerve interfacing
US20160331326A1 (en) * 2015-02-13 2016-11-17 National University Of Singapore Flexible neural strip electrodes, flexible neural ribbon electrodes and compartment based embedded nerve tissue electrode interfaces for peripheral nerves
CN110841186A (zh) * 2019-11-19 2020-02-28 华中科技大学 一种植入式外周神经电极
CN113041496A (zh) * 2021-03-19 2021-06-29 国家纳米科学中心 一种神经电刺激电极、其制备方法和植入方法

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060173263A1 (en) * 2003-02-04 2006-08-03 Jiping He Neural interface assembly and method for making and implanting the same
CN1911470A (zh) * 2006-07-28 2007-02-14 中国科学院上海微系统与信息技术研究所 一种集成药剂释放功能的植入式微电极、制作方法及应用
JP2009285154A (ja) * 2008-05-29 2009-12-10 Nippon Telegr & Teleph Corp <Ntt> 末梢神経型柔軟神経電極およびその作製方法
WO2012139124A1 (en) * 2011-04-07 2012-10-11 Georgia Tech Research Corporation Regenerative microchannel electrode array for peripheral nerve interfacing
US20160331326A1 (en) * 2015-02-13 2016-11-17 National University Of Singapore Flexible neural strip electrodes, flexible neural ribbon electrodes and compartment based embedded nerve tissue electrode interfaces for peripheral nerves
CN110841186A (zh) * 2019-11-19 2020-02-28 华中科技大学 一种植入式外周神经电极
CN113041496A (zh) * 2021-03-19 2021-06-29 国家纳米科学中心 一种神经电刺激电极、其制备方法和植入方法

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