WO2023240700A1 - 用于与可植入光学器件结合的柔性电极装置及制造方法 - Google Patents

用于与可植入光学器件结合的柔性电极装置及制造方法 Download PDF

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WO2023240700A1
WO2023240700A1 PCT/CN2022/102566 CN2022102566W WO2023240700A1 WO 2023240700 A1 WO2023240700 A1 WO 2023240700A1 CN 2022102566 W CN2022102566 W CN 2022102566W WO 2023240700 A1 WO2023240700 A1 WO 2023240700A1
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electrode
layer
flexible
flexible electrode
insulating layer
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PCT/CN2022/102566
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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 WO2023240700A1 publication Critical patent/WO2023240700A1/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
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0082—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes
    • A61B5/0084—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes for introduction into the body, e.g. by catheters
    • 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
    • A61B5/291—Bioelectric electrodes therefor specially adapted for particular uses for electroencephalography [EEG]
    • A61B5/293—Invasive
    • 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
    • A61B5/369—Electroencephalography [EEG]
    • A61B5/37—Intracranial electroencephalography [IC-EEG], e.g. electrocorticography [ECoG]
    • 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
    • A61B5/6868—Brain
    • 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
    • A61B2562/02—Details of sensors specially adapted for in-vivo measurements
    • A61B2562/0233—Special features of optical sensors or probes classified in A61B5/00
    • 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
    • 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 flexible electrode devices and manufacturing methods for use in combination with implantable optical devices, and specifically relates to being able to be matched with prisms for optical signal acquisition in deep brain regions, thereby achieving real-time synchronization of optical and electrical signals in the same area. Collected flexible electrode devices and manufacturing methods.
  • BCI Brain-Computer Interface
  • BMI Brain-Machine Interface
  • existing flexible electrodes are in contact with biological tissues such as brain tissue to receive electrical signals from the biological tissue for further processing, or to transmit external electrical signals to the biological tissue to, for example, apply Stimulate.
  • biological tissues such as brain tissue
  • optical devices for observing macroscopic changes in cell signals over time such as prisms for optical signal collection in deep brain areas.
  • Current techniques for measuring neural signals either acquire broad areas at low temporal resolution (such as calcium imaging) or record discrete regions at high temporal resolution (such as electrophysiology).
  • flexible electrodes need to be implanted in the brain together with prisms.
  • Electrodes combined with optical devices such as prisms need to be implanted into biological tissues and in long-term contact with the tissues.
  • electrodes In addition to transmitting as many signals as possible while being as small as possible, electrodes also need to be capable of simultaneous optical imaging and electrophysiological recording. without producing any light-induced artifacts in electrical recordings. Therefore, the electrode needs to have relatively good stability, biocompatibility, etc. to achieve long-term signal interaction; on the other hand, the electrode also needs to meet various requirements such as flexibility and light transmittance.
  • this application proposes a flexible electrode device and manufacturing method for combination with implantable optical devices.
  • a flexible electrode device for combination with an implantable optical device including an implantable and flexible high transmittance multi-channel mesh electrode, the multi-channel mesh
  • the mesh-shaped electrode is attached to the surface of the optical device and comes into contact with the biological tissue after the optical device is implanted, wherein the attachment portion of the multi-channel mesh electrode attached to the optical device includes: a wire located on the first insulating layer of the flexible electrode and between the second insulating layer; and electrode sites located on the second insulating layer and electrically coupled to the conductive wires through the through holes in the second insulating layer, wherein the flexible electrode device is configured to achieve the operation performed by the optical device Optical interaction is performed simultaneously with electrophysiological signal recording and electrical stimulation of neural activity by flexible electrodes.
  • an implantable electrode device including: a high transmittance multi-channel mesh electrode and an implantable optical device, wherein the multi-channel mesh electrode is attached to the optical device surface, and in contact with biological tissue after the optical device is implanted, wherein the attachment portion of the multi-channel mesh electrode to which the optical device is attached includes: a wire located between the first insulating layer and the second insulating layer of the flexible electrode; and electrode sites located over the second insulating layer and electrically coupled to the wires through the vias in the second insulating layer, wherein the electrode device is configured to enable neural activity by the flexible electrode while optical interaction is by the optical device Electrophysiological signal recording and electrical stimulation.
  • a method of manufacturing a flexible electrode device including a flexible electrode for combination with an implantable optical device as in the first aspect, the method comprising: Manufacturing a flexible separation layer on the substrate; manufacturing a first insulation layer, a conductor layer, a second insulation layer and an electrode site layer layer by layer on the flexible separation layer; and removing the flexible separation layer to separate the flexible electrode from the substrate; wherein, Before fabricating the electrode site layer, via holes are formed in the second insulating layer at positions corresponding to the electrode sites by patterning.
  • an implantation method of a flexible electrode device including a flexible electrode for combination with an implantable optical device as in the first aspect, the method comprising: Adjust the position of the flexible electrode so that the wire is aligned with the optical device; fix the optical device, drop pure water on the upper surface of the optical device, and move the electrode site of the flexible electrode into the water droplets on the upper surface of the optical device; blot the water droplets dry
  • the flexible electrode is brought into contact with the upper surface of the optical device; and the attached flexible electrode and the optical device are surgically implanted so that the attached part is in contact with the biological tissue.
  • an advantage of embodiments according to the present disclosure is that the flexible electrodes can be matched with prisms used for optical signal collection in deep brain areas, thereby achieving real-time synchronous collection of optical signals and electrical signals in the same area. Based on the observation of changes in macroscopic cell optical signals over time, local high-temporal resolution electrical signal information can be provided, which is conducive to in-depth analysis of dynamic network information in the later stage, thereby helping to understand network-level information. encoding mechanism.
  • FIG. 1 is a schematic diagram illustrating at least a portion of a flexible electrode device according to an embodiment of the present disclosure.
  • FIG. 2 is an exploded view illustrating at least a portion of a flexible electrode device according to an embodiment of the present disclosure.
  • FIG. 3 is a schematic diagram illustrating electrode sites of a flexible electrode device according to an embodiment of the present disclosure.
  • FIG. 4 is a schematic diagram showing a configuration of a flexible electrode device according to an embodiment of the present disclosure.
  • FIG. 5 is a schematic diagram showing another configuration of a flexible electrode device according to an embodiment of the present disclosure.
  • FIG. 6 is a diagram illustrating imaging effects obtained after implantation of a flexible electrode device according to an embodiment of the present disclosure.
  • FIG. 7 is a flowchart illustrating a method of manufacturing a flexible electrode according to an embodiment of the present disclosure.
  • FIG. 8 is a schematic diagram illustrating a method of manufacturing a flexible electrode according to an embodiment of the present disclosure.
  • FIG. 9 is a flowchart illustrating a method of implanting a flexible electrode device according to an embodiment of the present disclosure.
  • the technical solution of the present disclosure is mainly directed to flexible electrodes combined with optical devices.
  • the field requires applications that simultaneously collect optical signals and electrophysiological signals.
  • This requires the integration of invasive electrodes for electrical stimulation and electrical signal collection into the brain with optical devices such as prisms for collecting optical signals, which in addition to having the flexible characteristics of general brain implant electrodes , it also has adhesion to the surface of optical devices and light transmittance that is conducive to optical imaging.
  • Transparent graphene electrodes enable simultaneous optical imaging and electrophysiological recording without producing any light-induced artifacts in electrical recordings.
  • Stretchable carbon nanotube (CNT) transparent electrode arrays can simultaneously measure photoelectric signals in a mechanical deformation environment.
  • the flexible transparent array of 32 double-layered nanomesh microelectrodes allows simultaneous coupling of large, time-resolved electrophysiological data with optically measured, spatially resolved, and type-resolved single neuron activity with a high degree of uniformity and good biological Compatibility with state-of-the-art wireless recording and real-time artifact suppression systems.
  • the highly transparent double-layer nanomesh microelectrode array can perform in vivo two-photon imaging of single neurons in layer 2/3 of the visual cortex of awake mice, while performing high-fidelity simultaneous electrical recording of visual evoked activity through time-domain visual evoked potentials.
  • the measurements are at multiple unit activity bands and at lower frequencies.
  • the overall structure of the flexible electrode can be a strip-shaped high-transmittance multi-channel mesh electrode, which includes a wire portion connected to an external circuit, an electrode site, and an attachment portion attached to an optical device ( back-end part) and parts in contact with biological tissue, etc.
  • the flexible electrode has a multi-layer structure, specifically including a flexible separation layer 210, a first insulating layer 220, a circuit board connection layer 230, a wire layer 240, and a second insulating layer. 250, electrode site layer 260, etc.
  • the layers of the flexible electrode shown in Figures 1 and 2 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 conductors in the multi-channel mesh electrode include a plurality of conductors located in the conductor layer and spaced apart from each other, wherein the electrode sites in the multi-channel mesh electrode include respective vias in the bottom insulating layer.
  • a hole is a plurality of electrode sites electrically coupled to one of the plurality of conductors.
  • Multi-channel mesh electrodes have good flexibility and can be partially or fully implanted in biological tissues to collect electrical signals from or apply electrical signals to biological tissues.
  • the conductive layer of the multi-channel mesh electrode shown in Figure 1 includes a plurality of conductors, however it should be understood that in different embodiments, the electrodes in the present disclosure may include a single conductor or other specified number of conductors.
  • These wires may have widths and thicknesses on the nanometer or micrometer scale, and lengths that are orders of magnitude greater than the width and thickness, such as centimeters, as desired.
  • the shapes, sizes, etc. of these wires are not limited to the ranges listed above, but can be changed according to design needs.
  • the multi-channel mesh electrode may include a first insulating layer 220 at the bottom of the electrode and a second insulating layer 250 at the top of the electrode.
  • the insulating layer in the multi-channel mesh electrode may refer to the outer surface layer in 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 220 and 250 may include polyimide (PI), polydimethylsiloxane (PDMS), parylene (Parylene), epoxy resin, Polyamide-imide (PAI), SU-8 photoresist, silicone, silicone rubber, etc.
  • the insulating layers 220, 250 are also a major portion of the multi-channel mesh electrode providing 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 220, 250 may be 100 nm to 300 ⁇ m, preferably 300 nm to 20 ⁇ m, more preferably 1 ⁇ m to 2 ⁇ m, 500 nm to 1 ⁇ m, or the like.
  • each multi-channel mesh electrode may include one or more conductive wires located in the same conductive wire layer 240 .
  • the wire layer 240 of the multi-channel mesh electrode includes a plurality of wires, wherein each wire includes an elongated body portion and an end portion corresponding to a corresponding electrode site.
  • the line width of the wires and the spacing between the wires may be, for example, 10 nm to 500 ⁇ m, and the spacing between the wires may be as low as 10 nm, for example, preferably 100 nm to 30 ⁇ m. It should be understood that the shape, size, spacing, etc. of the conductors are not limited to the ranges listed above, but can be changed according to design needs.
  • the wires in the wire layer 240 may be a film structure including a plurality of superimposed layers in the thickness direction. These layered materials may be materials that enhance the wire's properties such as adhesion, ductility, and conductivity.
  • the wire layer 240 may include a superimposed conductive layer and an adhesion layer, wherein the adhesion layer in contact with the insulating layer 220 and/or 250 is titanium (Ti), titanium nitride (TiN), chromium (Cr).
  • the conductive layer is gold (Au), platinum (Pt), iridium (Ir), tungsten (W) , magnesium (Mg), molybdenum (Mo), platinum-iridium alloy, titanium alloy, graphite, carbon nanotubes, PEDOT and other materials with good conductivity.
  • the conductor layer can also be made of other conductive metal materials or non-metal materials, or can also be made of polymer conductive materials and composite conductive materials.
  • the thickness of the conductive layer of these wires is 5 nm to 200 ⁇ m, and the thickness of the adhesion layer is 1 to 50 nm.
  • the multi-channel mesh electrode may also include electrode sites in the electrode site layer 260 located above the first insulating layer 220. These electrode sites may be in contact with biological tissue to directly collect or apply electrical signals after the flexible electrode is implanted. .
  • the electrode sites in the electrode site layer 260 can be electrically coupled to corresponding wires through through holes in the first insulation layer 220 at positions corresponding to the electrode sites.
  • the multi-channel mesh electrode may correspondingly include a plurality of electrode sites in the electrode site layer 260 , and each of these electrode sites passes through the first insulating layer 220 A corresponding via is electrically coupled to one of the plurality of conductors.
  • Figure 3 shows a schematic diagram of an electrode site of a flexible electrode device according to an embodiment of the present disclosure. Specifically, (A) of FIG. 3 shows an enlarged view of the end of the wire corresponding to the electrode site in the conductor layer, and (B) of FIG. 3 shows an enlarged view of the end of the insulating layer corresponding to the electrode site, where respectively schematically One electrode site 310 and one via site 320 are shown.
  • each electrode site may have a corresponding conductor in conductor layer 240 .
  • Each electrode site may have planar dimensions on the micron scale and thickness on the nanoscale.
  • the electrode sites may include sites with a diameter of 1 ⁇ m to 500 ⁇ m, and a spacing between electrode sites may be 1 ⁇ m to 5 mm.
  • the electrode sites may take the shape of a circle, an ellipse, a rectangle, a rounded rectangle, a chamfered rectangle, etc. It should be understood that the shape, size and spacing of the electrode sites can be selected according to the conditions of the biological tissue area to be recorded.
  • the electrode sites in the electrode site layer 260 may be a thin film structure including a plurality of stacked layers in the thickness direction.
  • the material of the layer close to the wire layer 240 among the plurality of layers may be a material that can enhance the adhesion of the electrode site to the wire.
  • the electrode site layer 260 may be a metal film including two superimposed layers, wherein the first layer close to the wire layer 240 is Ti, TiN, Cr, Ta or TaN, and the electrode site layer The exposed second layer of 260 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.
  • 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 multi-channel mesh electrode may further include a bottom electrode site layer (not shown) located under the first insulating layer 220, which electrode site may be in contact with the biological body after the flexible electrode is implanted. Tissue contact to directly collect or apply electrical signals.
  • the bottom electrode site layer is similar to the electrode sites in the electrode site layer 260.
  • the electrode sites in the bottom electrode site layer can be connected to the electrode through the bottom insulating layer. Vias at corresponding locations of the sites are electrically coupled to corresponding conductors.
  • the electrode sites in the bottom electrode site layer may be located at opposite positions to the electrode sites in the electrode site layer 260 on both sides of the top and bottom of the multi-channel mesh electrode, and with Electrode sites in the oppositely located electrode site layer 260 are electrically coupled to the same conductor in the conductor layer 240 .
  • the electrode sites in the bottom electrode site layer may also be located at different positions on the top and bottom sides of the multi-channel mesh electrode from the electrode sites in the electrode site layer 260, 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 can also be electrically coupled to the electrode sites in the conductor layer 240 and the electrode site layer 260 Wires with different electrode locations.
  • the multi-channel mesh electrode may further include a flexible separation layer 210 .
  • the flexible separation layer 210 is mainly used in the manufacturing process of multi-channel mesh electrodes, and is made of metal or non-metal materials such as nickel (Ni), chromium (Cr), aluminum (Al).
  • the flexible separation layer 210 is also provided with an adhesion layer, the material of which includes any one of Ti, TiN, Cr, Ta or TaN or a combination thereof.
  • the bottom electrode site layer is an optional but not essential part of the multi-channel mesh electrode.
  • the multi-channel mesh electrode may only include the electrode site layer 260. Excludes bottom electrode site layer.
  • 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 rear end portion of the multi-channel mesh electrode may include at least one rear end site, the attachment portions of the multi-channel mesh electrode attached to the optical device each extend from the rear end portion, and the rear end portion
  • the site may be electrically coupled to one of the conductors and the back-end circuit through a through hole in the first insulating layer 220 and/or the second insulating layer 250 to achieve communication between the electrode site electrically coupled to the conductor and the back-end circuit.
  • Bidirectional signal transmission may refer to the circuit at the rear end of the multi-channel mesh electrode, such as a recording circuit, a processing circuit, etc. associated with the signal of the multi-channel mesh electrode.
  • the multi-channel mesh electrode can be coupled to the back-end circuit in a connected manner.
  • the Ball Gate Array (BGA) packaging site as the back-end site can be printed by
  • the flexible electrode can be released from the substrate before transfer (for example, by directly connecting the flexible electrode Peel it off from the base, or separate the flexible electrode from the base by removing the flexible separation layer), and connect the back end part through ball mounting patches and Anisotropic Conductive Film Bonding (ACF Bonding). Connect to the back-end circuit and then encapsulate using silicone etc.
  • BGA Ball Gate Array
  • PCB Printed Circuit Board
  • FPC Flexible Printed Circuit
  • ACF Bonding Anisotropic Conductive Film Bonding
  • 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. point.
  • 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 back-end site in the connection mode may include multiple layers in the thickness direction, and the material of the adhesive layer close to the wire layer 240 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 conductor layer 240 mentioned above.
  • Metal material, and the outermost layer among the multiple layers that may be exposed through the insulating layers 220 and 250 is an anti-oxidation protective layer.
  • the back-end site layer may include a superimposed conductive layer and an adhesive layer, wherein the adhesion layer close to the conductor layer 240 may be nanometer-scale layered to improve the connection between the back-end site layer and the conductor layer.
  • the adhesion layer as the middle layer of the soldering flux can be nickel (Ni), Pt or palladium (Pd), and the third layer as the outermost 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 in Figure 1 is a part connected to the back-end processing system or chip.
  • the size, spacing, shape, etc. of the sites can be changed according to the different connection methods of the back-end.
  • the multi-channel mesh electrode used has 512-channel electrode sites, including 4 128BGAs. It should be understood that other channel numbers of electrode sites may be included as desired, such as 32, 36, 64, 128 channels, etc.
  • the multi-channel mesh electrode may not include a site layer such as an electrode site layer (and/or a bottom electrode site layer), a rear end site layer, or the like.
  • the electrode sites of the multi-channel mesh electrode 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.
  • the electrode sites for sensing and applying electrical signals can be in direct contact with the tissue area into which the electrode wire is implanted.
  • each electrode site can be electrically coupled to the conductor layer in the conductor layer.
  • Corresponding wires are exposed to the outer surface of the electrode wire through corresponding through holes in the top insulating layer or the bottom insulating layer and are in contact with the biological tissue.
  • FIG. 4 is a schematic diagram showing a configuration of a flexible electrode device according to an embodiment of the present disclosure.
  • the optical device that needs to be implanted in the brain is the prism 410 as an example.
  • the multi-channel mesh electrode 420 is attached to the end of the prism 410 as shown in Figure 4 (A), so that the multi-channel mesh electrode 420 is included in the patch.
  • the electrode sites in the attached portion 430 are combined with the prism 410 to produce an effect as shown in (B) of FIG. 4 .
  • FIG. 5 is a schematic diagram showing another configuration of a flexible electrode device according to an embodiment of the present disclosure.
  • FIG. 5(A) shows the arrangement state after the optical device (prism) attached with the flexible electrode is implanted in the brain. It can be seen that the end of the prism is connected to the brain via the attached part of the electrode. Direct contact with biological tissue.
  • FIG. 5(B) shows the arrangement state after the prism to which the flexible electrode is attached has been removed from the brain implantation site.
  • the multi-channel mesh electrode is attached to the surface of the optical device through van der Waals forces, thereby forming a strong adhesion between the electrode and the prism, so that the flexible electrode device is integrally implanted in the brain. It has friction with the surface of the cortex and will not fall off after being taken out.
  • the aforementioned flexible electrode device as a whole can be attached to the cerebral sulcus.
  • FIG. 6 is a diagram illustrating imaging effects obtained after implantation of a flexible electrode device according to an embodiment of the present disclosure. As shown in the figure, after imaging the brain, the electrode sites at the ends of the flexible electrodes according to the present disclosure can be seen, and the part in the wire spacing is not blocked, that is, the optical imaging of the prism can still be achieved even with the flexible electrodes attached. can be delivered effectively.
  • method 7000 may include: at S701, manufacturing a flexible separation layer on the substrate; at S702, manufacturing a first insulation layer, a conductor layer, a second insulation layer and a second insulation layer on the flexible separation layer layer by layer.
  • the electrode site layer wherein, before manufacturing the electrode sites, through holes are formed in the first insulating layer at positions corresponding to the electrode sites by patterning; and at S703, the flexible separation layer is removed to separate from the substrate Flexible electrodes.
  • FIG. 8 is a schematic diagram illustrating a method 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. 8 .
  • View (A) of Figure 8 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 8 illustrates the steps of fabricating a flexible release 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 8 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 8 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 8 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.
  • 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 8 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 outline of the top insulating layer is realized and the outline of the through hole is realized in the position of the top insulating layer corresponding to the electrode site.
  • 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 8 shows the fabrication of the top electrode site layer over the top insulating layer.
  • the method 9000 may include: at S901, adjusting the position of the flexible electrode to align the conductor with the optical device, including making the conductor longitudinally a first distance lower than the upper end face of the optical device, and adjusting the position of the electrode laterally so that the conductor at the rear end of the electrode spreads out.
  • the first distance is 0mm-2.5mm
  • the flexible electrode is laterally 3mm-20mm away from the edge of the optical device.
  • the optical device is fixed, pure water is dropped on the upper surface of the optical device, and the electrode site of the flexible electrode is moved into the water droplets on the upper surface of the optical device, including exposing the optical device to a second distance for clamping and fixing. , the electrode sites are adjusted in the water droplet so that the electrode sites are flat on the upper surface of the optical device. Preferably, the second distance is 3-10mm.
  • the water droplets are sucked dry so that the flexible electrode is attached to the upper surface of the optical device; and at step S904, the attached flexible electrode and the optical device are surgically implanted so that the attached part is in contact with the biological tissue.
  • a transparent adhesive may be dripped on the upper surface of the optical device to attach the electrode site portion of the flexible electrode to the upper surface of the optical device.
  • the electrode wire and the circular site at the front end are first detached from the flexible separation layer, and then the electrode site area is moved to the water droplet on the upper surface of the prism, and the electrode site area is adjusted in the water droplet Lay it flat on the upper surface of the prism, and then absorb the water.
  • the electrode array will be closely attached to the upper surface of the prism. Then, attach the rear wire to the side wall of the prism, and the assembly is completed.
  • the assembled prism with flexible electrode attached use the following steps to implant it into the corresponding area of the brain: First, determine the implantation area of the brain, place the assembled electrodes and prism above the implantation area, and pass the prism through the prism. The support device adjusts the position of the prism so that it faces the hole to be implanted, thereby pressing the prism into the corresponding area. It should be noted that the conductor must have a certain degree of freedom of movement during the operation to avoid breakage of the conductor or movement of the site area. Then, lay the back-end wire flat on the surface of the skull so that the prism is tightly combined with the skull, and move the supporting device upward to separate it from the prism. Thereafter, electrical signal recording can be carried out after the prism and electrode are completely implanted, and the field potential signal can be recorded relatively stably. Calcium signal recording requires waiting time to allow the tissue to fully recover.
  • the flexible electrode array using stretchable carbon nanotubes can have, for example, 16 recording sites, the electrode recording site size is 100 ⁇ m ⁇ 100 ⁇ m, and the lead width is 50 ⁇ m.
  • the flexible electrode array using transparent graphene can have, for example, 8-16 recording sites, and the recording site size is 300m ⁇ 300 ⁇ m.
  • Stretchable carbon nanotubes and graphene use PDMS as the substrate and have a thickness of more than 100 ⁇ m, so the preparation process is more complex and the adhesion is insufficient.
  • the flexible electrodes in the embodiments of the present disclosure have electrode sites with smaller sizes, and the line widths can be less than 1.5 ⁇ m or even hundreds of nanometers, allowing for a higher number of channels with the same electrode size.
  • the line widths can be less than 1.5 ⁇ m or even hundreds of nanometers, allowing for a higher number of channels with the same electrode size.
  • a 64-channel electrode can be realized, and hundreds or thousands of channels can be realized; on the other hand, the thickness of the electrode is only 1 ⁇ m, so it can achieve technical effects of being thinner, more transparent, and better adherent.
  • 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

一种用于与可植入光学器件结合的柔性电极装置，包括：可植入且柔性的高透光率多通道网状电极，网状电极附接于光学器件表面，并且在光学器件被植入后与生物组织接触，多通道网状电极与光学器件附接的贴附部分包括：导线，位于电极的第一绝缘层(220)和第二绝缘层(250)之间；以及电极位点(310)，位于第二绝缘层(250)之上，并且通过第二绝缘层(250)中的通孔电耦合到导线。柔性电极装置能实现在由光学器件进行光学交互的同时由电极进行神经活动电生理信号记录和电刺激。

Description

用于与可植入光学器件结合的柔性电极装置及制造方法 技术领域
本公开涉及用于与可植入光学器件结合的柔性电极装置及制造方法，并且具体地涉及能够与用于深部脑区光学信号采集的棱镜匹配，从而实现相同区域光学信号和电信号的实时同步采集的柔性电极装置及制造方法。
背景技术
脑机接口(Brain-Computer Interface，BCI，也可以被称为Brain-Machine Interface，BMI)***是一种用于实现脑和外部世界之间的直接信号传输的***，其不依赖于传统的通过外周神经***等组成的通路来实现神经信号的采集和输出，在医疗领域和非医疗领域中具有广泛的应用前景。
现有的柔性电极作为脑机接口***的重要组成部分，其与诸如脑组织之类的生物组织接触以从生物组织接收电信号以供进一步处理，或将外部电信号传输到生物组织以例如施加刺激。另一方面，已有观测宏观的细胞信号随时间变化的光学器件，诸如用于深部脑区光学信号采集的棱镜等。目前测量神经信号的技术或者以低时间分辨率(如钙成像)采集广阔区域，或者以高时间分辨率(如电生理学)记录离散区域。为了将光信号交互与电生理技术进行整合，需要配合棱镜共同植入脑区的柔性电极。
与棱镜等光学器件结合的电极除了需要植入到生物组织中并与组织长期接触、需要在体积尽量小的情况下传输尽量多的信号之外，还需要满足同时进行光学成像和电生理记录，而不会在电记录中产生任何光致伪影。因此该电极需要具有相对好的稳定性、生物相容性等，以实现长期信号交互；另一方面，该电极还需要满足柔性、透光性等多方面的要求。
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。
概括而言，本申请提出了一种用于与可植入光学器件结合的柔性电极装置及制造方法。
根据本公开的实施例的第一方面，提供了一种用于与可植入光学器件结合的柔性电极装置，包括可植入且柔性的高透光率多通道网状电极，该多通道网状电极附接于光学器件表面，并且在光学器件被植入后与生物组织接触，其中多通道网状电极与光学器件附接的贴附部分包括：导线，位于柔性电极的第一绝缘层和第二绝缘层之间；以及电极位点，位于第二绝缘层之上，并且通过第二绝缘层中的通孔电耦合到导线，其中所述柔性电极装置被配置为实现在由光学器件进行光学交互的同时由柔性电极进行神经活动电生理信号记录和电刺激。
根据本公开的实施例的第二方面，提供了一种可植入电极装置，包括：高透光率多通道网状电极以及可植入光学器件，其中多通道网状电极附接于光学器件表面，并且在光学器件被植入后与生物组织接触，其中多通道网状电极与光学器件附接的贴附部分包括：导线，位于柔性电极的第一绝缘层和第二绝缘层之间；以及电极位点，位于第二绝缘层之上，并且通过第二绝缘层中的通孔电耦合到导线，其中电极装置被配置为实现在由光学器件进行光学交互的同时由柔性电极进行神经活动电生理信号记录和电刺激。
根据本公开的实施例的第三方面，提供了一种柔性电极装置的制造方法，该柔性电极装置包括如第一方面的用于与可植入光学器件结合的柔性电极，该方法包括：在基底之上制造柔性分离层；在柔性分离层之上逐层制造第一绝缘层、导线层、第二绝缘层和电极位点层；以及去除柔性分离层以从基底分离出柔性电极；其中，在制造电极位点层之前，通过图形化在第二绝缘层中的与电极位点对应的位置制造出通孔。
根据本公开的实施例的第四方面，提供了一种柔性电极装置的植入方法，该柔性电极装置包括如第一方面的用于与可植入光学器件结合的柔性电极，该方法包括：调整柔性电极的位置使得导线与光学器件对齐；固定光学器件，并在光学器件的上表面滴上纯水，将柔性电极的电极位点移到光学器件的上表面的水滴里；将水滴吸干使得柔性电极与光学器件的上表面贴合；以及对附接的柔性电极与光学器件进行手术植入，以所得贴附部分与生物组织接触。
根据本公开的实施例的优点在于柔性电极能够与用于深部脑区光学信号采集的棱镜匹配，从而实现相同区域光学信号和电信号的实时同步采集。在观测到宏观的细胞光学信号随时间变化的基础上，可以提供局部的高时间分辨率的电信号信息，有利于后期对动态的网络化信息进行深入的分析，从而帮助理解网络化层面的信息编码机制。
应当认识到，上述优点不需全部集中在一个或一些特定实施例中实现，而是可以部分分散在根据本公开的不同实施例中。根据本公开的实施例可以具有上述优点中的一个或一 些，也可以替代地或者附加地具有其它的优点。
通过以下参照附图对本发明的示例性实施例的详细描述，本发明的其它特征及其优点将会变得更为清楚。
附图说明
图1是示出了根据本公开的实施例的柔性电极装置的至少一部分的示意图。
图2是示出了根据本公开的实施例的柔性电极装置的至少一部分的分解图。
图3是示出了根据本公开的实施例的柔性电极装置的电极位点的示意图。
图4是示出了根据本公开的实施例的柔性电极装置的一个配置示意图。
图5是示出了根据本公开的实施例的柔性电极装置的另一个配置示意图。
图6是示出了根据本公开的实施例的柔性电极装置植入后的获得的成像效果图。
图7是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8是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9是示出了根据本公开的实施例的植入柔性电极装置的方法的流程图。
具体实施方式
下面将参照附图来详细描述本公开的各种示例性实施例。应注意到：除非另外具体说明，否则在这些实施例中阐述的部件和步骤的相对布置、数字表达式和数值不限制本公开的范围。
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。
概括而言，本公开的技术方案主要针对与光学器件相结合的柔性电极。为了实现在测量神经信号的同时以高时间分辨率记载离散区域的技术目的，本领域需要同时采集光学信号与电生理信号的应用。这要求在对脑部进行诸如采集光学信号的棱镜之类的光学器件时整合地植入进行电刺激和电信号收集的侵入式电极，该电极除了具有一般脑部植入电极的 柔性特征之外，还具备针对光学器件表面的贴附性以及有利于光学成像的透光性。
现有技术中解决该技术问题的方案主要是使用不同的材质或结构的透明电极。透明石墨烯电极能够同时进行光学成像和电生理记录，而不会在电记录中产生任何光致伪影。可拉伸碳纳米管(CNT)透明电极阵列可在机械形变环境中同时测量光电信号。32个双层纳米网微电极的柔性透明阵列允许大的、时间分辨的电生理数据与光学测量的、空间分辨的和类型分辨的单个神经元活动同时耦合，具有高度的均匀性，良好的生物相容性，以及与最先进的无线记录和实时伪影抑制***的兼容性。高度透明的双层纳米网微电极阵列可以对清醒小鼠视皮层2/3层的单个神经元进行活体双光子成像，同时对视觉诱发活动进行高保真的同步电记录，通过时域视觉诱发电位的测量，在多个单位的活动带和较低的频率。应用植入式EEG电极和钙成像联合记录用于癫痫研究。非侵入式多电极阵列与钙指示剂结合，对组织切片进行研究。
图1和图2分别示出了根据本公开的实施例的柔性电极装置的至少一部分的示意图和分解图。如图1所示，柔性电极的整体构造可以是条状的高透光率多通道网状电极，其中包括连接到外部电路的导线部分、电极位点、贴附到光学器件的贴附部分(后端部分)以及与生物组织的接触部分等。具体地，从图2可以清楚地看出，柔性电极为多层结构，具体而言，包括柔性分离层210、第一绝缘层220、与线路板连接层230、导线层240、第二绝缘层250、电极位点层260等。应理解的是，图1和图2中示出的柔性电极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它层。
如图1所示，多通道网状电极中的导线包括位于导线层中并且彼此间隔开的多个导线，其中，多通道网状电极中的电极位点包括各自通过底部绝缘层中的相应通孔与该多个导线之一电耦合的多个电极位点。多通道网状电极具有良好的柔性，其可以部分或全部地可植入生物组织中以从生物组织采集或向生物组织施加电信号。图1中示出的多通道网状电极的导电层包括多个导线，然而应理解的是，在不同的实施例中，本公开中的电极可以包括单个导线或其它指定数量的导线。这些导线可以具有纳米级或微米级的宽度和厚度，以及根据需要与宽度和厚度相比大若干数量级(诸如，厘米级)的长度。在根据本公开的实施例中，这些导线的形状、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。
具体而言，多通道网状电极可以包括位于电极底部的第一绝缘层220和位于电极顶部的第二绝缘层250。多通道网状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220、250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。此外，绝缘层220、250还是多通道网状电极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220、250的厚度可以为100nm至300μm，优选地为300nm至20μm，更优选地为1μm至2μm、500nm至1μm等。
多通道网状电极中的导线层分布在第一绝缘层220和第二绝缘层250之间的导线层240中。在根据本公开的实施例中，每个多通道网状电极可以包括位于同一导线层240中的一个或多个导线。例如，从图2中可以清楚地看出，多通道网状电极的导线层240包括多个导线，其中每个导线包括细长的主体部分和与相应电极位点对应的端部。导线的线宽和各导线之间的间距例如可以为10nm至500μm，各导线之间的间距例如可以低至10nm，例如，优选地为100nm至30μm。应理解的是，导线的形状、尺寸、间距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240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诸如粘附性、延展性、导电性的材料。作为非限制性示例，导线层240可以包括叠加的导电层和粘附层，其中，与绝缘层220和/或250接触的粘附层为钛(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，导电层为金(Au)、铂(Pt)、铱(Ir)、钨(W)、镁(Mg)、钼(Mo)、铂铱合金、钛合金、石墨、碳纳米管、PEDOT等导电性良好的材料。应理解的是，导线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，也可以采用高分子导电材料以及复合导电材料制成。在一个非限制性实施例中，这些导线的导电层的厚度为5nm至200μm，粘附层的厚度为1至50nm。
多通道网状电极还可以包括位于第一绝缘层220之上的电极位点层260中的电极位点，这些电极位点在植入柔性电极后可与生物组织接触以直接采集或施加电信号。在多通道网状电极中，电极位点层260中的电极位点可以通过第一绝缘层220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。在多通道网状电极包括多个导线的情况下，该多通道网状电极可以相应地包括电极位点层260中的多个电极位点，并且这些电极位点各自通过第一绝缘层220中的相应通孔与多个导线之一电耦合。例如，图3示出了根据本公开的 实施例的柔性电极装置的电极位点的示意图。具体地，图3的(A)放大示出了导线层中对应于电极位点的导线末端，图3的(B)放大示出了绝缘层中对应于电极位点的末端，其中分别示意地示出了一个电极位点310和一个通孔位置320。
在一个非限制性实施例中，每个电极位点可以均具有导线层240中的对应的导线。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，电极位点可以包括直径为1μm至500μm的位点，各电极位点之间的间距可以为1μm至5mm。在根据本公开的实施例中，电极位点可以采取圆形、椭圆形、矩形、圆角矩形、倒角矩形等形状。应理解的是，电极位点的形状、大小和间距等可以根据所需记录的生物组织区域的情况来选择。
在根据本公开的实施例中，电极位点层260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240的分层的材料可以为可增强电极位点与导线的粘附的材料。作为非限制性示例，电极位点层260可以是包括叠加的两个分层的金属薄膜，其中，接近导线层240的第一分层为Ti、TiN、Cr、Ta或TaN，电极位点层260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。
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，多通道网状电极还可以包括位于第一绝缘层220之下的底部电极位点层(未示出)，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。具体而言，底部电极位点层与电极位点层260中的电极位点类似，在多通道网状电极中，底部电极位点层中的电极位点可以通过底部绝缘层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，底部电极位点层中的电极位点可以与电极位点层260中的电极位点位于多通道网状电极的顶部和底部两侧的相对位置处，并且与位于相对位置的电极位点层260中的电极位点电耦合到导线层240中的同一导线。在根据本公开的实施例中，底部电极位点层中的电极位点也可以与电极位点层260中的电极位点位于多通道网状电极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，底部电极位点层中的电极位点也可以电耦合到导线层240中的与电极位点层260中的电极位点不同的导线。
在根据本公开的实施例中，多通道网状电极还可以包括柔性分离层210。柔性分离层210主要用于多通道网状电极的制造过程，其材料镍(Ni)、铬(Cr)、铝(Al)等金属或者非金属材料。柔性分离层210还设置有粘附层，其材料包括Ti、TiN、Cr、Ta或TaN中的任一种或其组合。
应理解的是，底部电极位点层是多通道网状电极的可选而非必要的一部分，例如图2中所示的分解结构中，多通道网状电极可以仅包括电极位点层260而不包括底部电极位点层。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，在此不作赘述。
在根据本公开的实施例中，多通道网状电极的后端部分可以包括至少一个后端位点，多通道网状电极贴附到光学器件的贴附部分各自从后端部分延伸，后端位点可以通过第一绝缘层220和/或第二绝缘层250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多通道网状电极后端的电路，诸如与多通道网状电极的信号相关联的记录电路、处理电路等。在根据本公开的实施例中，多通道网状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***，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。
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。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240的黏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240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220、250暴露的最外层为防氧化的保护分层。作为非限制性示例，后端位点层可以包括叠加的 导电层和粘附层，其中，接近导线层240的粘附层可以为纳米量级的分层，以改善后端位点层与导线层240之间的粘附，作为助焊中间分层的粘附层可以为镍(Ni)、Pt或钯(Pd)，作为最外层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中的后端位点层作为与后端处理***或芯片连接的部分，其位点的大小、间距、形状等可以根据可以后端的不同连接方式来更换设计，在一个非限制性实施例中，采用的多通道网状电极具有512通道的电极的位点，包括4个128BGA。应理解的是，可以根据需要包括其他通道数的电极位点，诸如32、36、64、128通道等。
在根据本公开的实施例中，多通道网状电极可以不包括诸如电极位点层(以及/或者底部电极位点层)、后端位点层等位点层。在这种情况下，多通道网状电极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丝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丝的外表面并与生物组织接触。
图4是示出了根据本公开的实施例的柔性电极装置的一个配置示意图。需要植入脑补的光学器件以棱镜410为例，将多通道网状电极420如图4的(A)所示地贴附到棱镜410的端部，使得多通道网状电极420包含在贴附部分430中的电极位点与棱镜410结合为如图4的(B)所示的效果。
图5是示出了根据本公开的实施例的柔性电极装置的另一个配置示意图。具体地，图5的(A)中示出了将贴附有柔性电极的光学器件(棱镜)植入脑部后的配置状态，可以看出棱镜的端部经由电极的贴附部分与脑部生物组织直接接触。图5的(B)中示出了将贴附有柔性电极的棱镜从脑部植入位置取出后的配置状态。在一个非限制性实施例中，多通道网状电极通过范德华力附接到光学器件的表面，从而形成电极与棱镜之间较强的贴附性，使得柔性电极装置整体植入脑部后虽然与皮层表面有摩擦，取出后仍不会掉落。此外，在另一个实施例中，前述的柔性电极装置整体能够贴附到大脑沟回中。
图6是示出了根据本公开的实施例的柔性电极装置植入后的获得的成像效果图。如图所示对脑部成像后能看到根据本公开的柔性电极端部的电极位点，而导线间距中的部分未被遮挡，即棱镜的光学成像在有柔性电极贴附的情况下仍能有效传递。
图7是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。在本公开中，可以采取基于微型电子机械***(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2所示，方法7000可以包括：在S701处，在基底之上制造柔性分离层；在S702处，在柔性分离层之上逐层制造第一绝缘层、导线层、第二绝缘层和电极位点层，其中，在制造电极位点之前，通过图形化在第一绝缘层中的与电极位点对应的位置制造出通孔；以及在S703处，去除柔性分离层以从基底分离出柔性电极。
图8是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。结合图8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8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8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8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8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8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1中所示的导线层240的图案，即，从后端部分延伸的各个电极丝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，将掩模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8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中所示的第一绝缘层的图案，即，从后端部分延伸的各个电极丝中的一个或多个导线上实现的顶部绝缘层的轮廓并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，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8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是示出了根据本公开的实施例的植入柔性电极装置的方法的流程图。该方法9000可以包括：在S901处，调整柔性电极的位置使得导线与光学器件对齐，包括使得导线纵向上低于所述光学器件上端面第一距离,横向上调整电极位置使电极后端导线展平以避免折叠。优选地，第一距离为0mm-2.5mm，柔性电极横向上距离光学器件边缘3mm-20mm。在S902处，固定光学器件，并在光学器件的上表面滴上纯水，将柔性电极的电极位点移到光学器件的上表面的水滴里，包括使得光学器件露出第二距离以便夹持固定，在水滴中对电极位点进行调整使得电极位点平铺在光学器件的上表面。优选地，第二距离为3-10mm。在S903处，将水滴吸干使得柔性电极与光学器件的上表面贴合；以及在步骤S904处，对附接的柔性电极与光学器件进行手术植入，以所得贴附部分与生物组织接触。可替代地，也可以在光学器件的上表面滴上透明黏合剂，以将柔性电极的电极位点部分附接到光学器件的上表面。
在一个非限制性实施例中，首先将电极导线以及前端的圆形位点从柔性分离层脱离出来，然后，将电极位点区域移到棱镜上表面水滴里，在水滴中调整电极位点区域使之平铺在棱镜上表面，后将水吸干，电极阵列会与棱镜上表面紧密贴合，其后将后端导线贴在棱镜侧壁，装配完成。
对于已经完成装配的贴附有柔性电极的棱镜，采用以下步骤植入到脑部相应区域：首先，确定脑部的植入区域，将装配好的电极与棱镜置于植入区域上方，通过棱镜的支持装置调整棱镜位置，使之正对要植入的孔，从而将棱镜压入对应区域。需要注意的是，操作过程中需保持导线有一定的移动自由度，避免导线断裂或者位点区域位置发生移动。接着，将后端导线平铺在颅骨表面，使得棱镜与颅骨紧密结合，并向上移动支持装置使之与棱镜 分离。此后，待棱镜与电极完成植入后即可进行电信号记录，可以比较稳定的记录到场电位信号，钙信号记录需等待时间，使组织充分恢复。
与现有技术采用的技术方案相比，根据本公开的实施例具有更有利的技术效果。采用可拉伸碳纳米管的柔性电极阵列可以具有诸如16个记录位点，电极记录位点尺寸为100μm×100μm，引线宽度为50μm。采用透明石墨烯的柔性电极阵列可以具有诸如8-16个记录位点，极记录位点尺寸为300m×300μm。可拉伸碳纳米管和石墨烯采用PDMS作为基底，并且厚度100μm以上，因此制备工艺更复杂，并且贴附度不足。相比之下，本公开的实施例中的柔性电极具有尺寸更小的电极位点，线宽可以小于1.5μm以至百纳米，使得在电极尺寸相同的情况下具备更高的通道数。实验中可以实现64通道的电极，并且可以实现上百或上千数量级的通道；另一方面，电极厚度只有1μm，因此能够实现更薄、更透明以及贴附性更好的技术效果。
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 (25)

  1. 一种用于与可植入光学器件结合的柔性电极装置，包括：
    可植入且柔性的高透光率多通道网状电极，所述多通道网状电极附接于光学器件表面，并且在所述光学器件被植入后与生物组织接触，
    其中所述多通道网状电极与所述光学器件附接的贴附部分包括：
    导线，所述导线位于所述柔性电极的第一绝缘层和第二绝缘层之间；以及
    电极位点，所述电极位点位于所述第二绝缘层之上，并且通过所述第二绝缘层中的通孔电耦合到所述导线，
    其中所述柔性电极装置被配置为实现在由所述光学器件进行光学交互的同时由柔性电极进行神经活动电生理信号记录和电刺激。
  2. 根据权利要求1所述的柔性电极装置，其中：
    所述光学器件包括光纤、棱镜、梯度折射率透镜。
  3. 根据权利要求1所述的柔性电极装置，其中：
    所述多通道网状电极中的导线包括位于导线层中并且彼此间隔开的多个导线，以及
    所述多通道网状电极中的电极位点包括各自通过所述第二绝缘层中的相应通孔与所述多个导线之一电耦合的多个电极位点。
  4. 根据权利要求1所述的柔性电极装置，还包括：
    后端部分，包括至少一个后端位点，
    其中，所述贴附部分各自从所述后端部分延伸，并且
    每个后端位点通过所述第一绝缘层或所述第二绝缘层中的通孔电耦接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。
  5. 根据权利要求1所述的柔性电极装置，还包括：
    柔性分离层，所述柔性分离层的材料包括镍、铬、铝或者非金属材料。
  6. 根据权利要求5所述的柔性电极装置，其中：
    所述柔性分离层还设置有粘附层，所述粘附层的材料包括铬、钽、氮化钽、钛或氮化钛中的任一种或其组合。
  7. 根据权利要求1所述的柔性电极装置，其中：
    所述第一绝缘层和所述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、聚乳酸、聚乳酸-羟基乙酸共聚物、SU8光刻胶、硅胶、硅橡胶中的任一种或其组合。
  8. 根据权利要求1所述的柔性电极装置，其中：
    第一绝缘层和第二绝缘层的厚度为100nm至300μm。
  9. 根据权利要求1所述的柔性电极装置，其中：
    所述多通道网状电极中的电极位点包括导电层，并设置有粘附层。
  10. 根据权利要求9所述的柔性电极装置，其中：
    所述电极位点的导电层的材料为金、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，以及
    所述粘附层的材料包括铬、钽、氮化钽、钛或氮化钛中的任一种或其组合。
  11. 根据权利要求10所述的柔性电极装置，其中：
    所述电极位点的导电层的厚度为5nm至200μm，以及
    所述粘附层的厚度为1至50nm。
  12. 根据权利要求1所述的柔性电极装置，其中：
    所述多通道网状电极中的导线的线宽和各导线之间的间距为10nm至500μm。
  13. 根据权利要求1所述的柔性电极装置，其中：
    所述多通道网状电极中的导线包括导电层，并设置有粘附层。
  14. 根据权利要求13所述的柔性电极装置，其中：
    所述导线的导电层的材料为金、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，以及
    所述粘附层的材料包括铬、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14所述的柔性电极装置，其中：
    所述导线的导电层的厚度为5nm至200μm，以及
    所述粘附层的厚度为1至50nm。
  16. 根据权利要求1所述的柔性电极装置，其中：
    电极位点的形状为圆形、椭圆形、矩形、圆角矩形、倒角矩形，电极位点的最长边或直径为1μm至500μm，各电极位点之间的间距为1μm至5mm。
  17. 根据权利要求1所述的柔性电极装置，其中：
    后端位点为直径为50μm至2000μm的球栅阵列封装位点或边长为50μm至2000μm的圆形、椭圆形、矩形、圆角或倒角矩形位点。
  18. 根据权利要求1所述的柔性电极装置，其中：
    所述多通道网状电极通过范德华力附接到可植入光学器件表面。
  19. 根据权利要求1所述的柔性电极装置，其中：
    所述多通道网状电极通过生物兼容性胶黏剂附接到可植入光学器件表面。
  20. 根据权利要求1所述的柔性电极装置，其中：
    所述柔性电极装置能够贴附到大脑沟回中。
  21. 一种可植入电极装置，包括：
    高透光率多通道网状电极以及可植入光学器件，
    其中所述多通道网状电极附接于光学器件表面，并且在所述光学器件被植入后与生物组织接触，
    其中所述多通道网状电极与所述光学器件附接的贴附部分包括：
    导线，所述导线位于所述柔性电极的第一绝缘层和第二绝缘层之间；以及
    电极位点，所述电极位点位于所述第二绝缘层之上，并且通过所述第二绝缘层中的通孔电耦合到所述导线，
    其中所述电极装置被配置为实现在由所述光学器件进行光学交互的同时由柔性电极进行神经活动电生理信号记录和电刺激。
  22. 一种柔性电极装置的制造方法，所述柔性电极装置包括如权利要求1-20中的任一项所述的用于与可植入光学器件结合的柔性电极，所述方法包括：
    在基底之上制造柔性分离层；
    在柔性分离层之上逐层制造第一绝缘层、导线层、第二绝缘层和电极位点层；以及
    去除柔性分离层以从基底分离出柔性电极；
    其中，在制造电极位点层之前，通过图形化在第二绝缘层中的与电极位点对应的位置制造出通孔。
  23. 一种柔性电极装置的植入方法，所述柔性电极装置包括如权利要求1-20中的任一项所述的用于与可植入光学器件结合的柔性电极，所述方法包括：
    调整柔性电极的位置使得导线与所述光学器件对齐；
    固定所述光学器件，使得柔性电极与所述光学器件的上表面贴合；以及
    对附接的所述柔性电极与所述光学器件进行植入，以所得所述贴附部分与生物组织接触。
  24. 根据权利要求23所述的植入方法，其中：
    在所述光学器件的上表面滴上可蒸发的液体，将所述柔性电极的电极位点移动到所述液体中，并且将所述液体蒸干以实现贴合。
  25. 根据权利要求23所述的植入方法，其中：
    使用透明黏合剂将所述柔性电极贴合到所述光学器件的上表面。
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