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WO2023240686A1 - 用于与seeg电极结合的柔性电极装置及其制造方法 - Google Patents

用于与seeg电极结合的柔性电极装置及其制造方法 Download PDF

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Publication number
WO2023240686A1
WO2023240686A1 PCT/CN2022/102151 CN2022102151W WO2023240686A1 WO 2023240686 A1 WO2023240686 A1 WO 2023240686A1 CN 2022102151 W CN2022102151 W CN 2022102151W WO 2023240686 A1 WO2023240686 A1 WO 2023240686A1
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Prior art keywords
electrode
flexible
layer
seeg
insulating layer
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PCT/CN2022/102151
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English (en)
French (fr)
Inventor
赵郑拓
李雪
冯成聪
杨佳宁
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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 WO2023240686A1 publication Critical patent/WO2023240686A1/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
    • A61B5/279—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
    • A61B5/25—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
    • A61B5/316—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
    • A61B5/40—Detecting, measuring or recording for evaluating the nervous system
    • A61B5/4076—Diagnosing or monitoring particular conditions of the nervous system
    • A61B5/4094—Diagnosing or monitoring seizure diseases, e.g. epilepsy
    • 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
    • A61N1/0526—Head electrodes
    • A61N1/0529—Electrodes for brain stimulation
    • A61N1/0534—Electrodes for deep brain stimulation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/3606—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
    • A61N1/36064—Epilepsy
    • 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
    • A61N1/37514—Brain implants
    • 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 flexible electrode devices for use in conjunction with stereotactic electroencephalography (SEEG) electrodes and methods of manufacturing the same, and in particular to methods that can achieve secure attachment without the use of specific adhesives and without significantly affecting the SEEG electrodes.
  • SEEG stereotactic electroencephalography
  • SEEG technology uses a minimally invasive method and does not require surgical incisions. It only requires drilling 2mm micro holes in the scalp and skull to place deep electrodes into specific locations deep in the brain. Therefore, this technology is suitable for patients with epilepsy who require EEG localization of intracranial electrodes.
  • SEEG technology introduces the positioning method from 2D to the 3D level. It can be directly placed in the deep frontal lobe, medial surface of the brain, cingulate gyrus, medial temporal lobe, etc.
  • Conventional cortical electrodes cannot reach any target parts in the brain, providing comprehensive three-dimensional coverage of the brain. , so as to achieve the purpose of accurately locating the focus and improving the treatment effect. It is a brand-new epilepsy focus positioning technology, which plays an important role in identifying the focus of epilepsy patients.
  • This application proposes a flexible electrode device for combination with SEEG electrodes and a manufacturing method thereof.
  • a flexible electrode device for combination with a SEEG electrode including: at least one implantable and flexible electrode wire, wherein each electrode wire respectively includes: a wire located at between the first insulating layer and the second insulating layer of the flexible electrode; and an electrode site located above the second insulating layer and electrically coupled to the conductor through a through hole in the second insulating layer, wherein the at least one electrode
  • the wire is configured to attach to the SEEG electrode and come into contact with biological tissue after the SEEG electrode is implanted.
  • a method for manufacturing a flexible electrode device includes a flexible electrode for combination with a SEEG electrode as described in the first aspect.
  • the method includes: manufacturing a flexible separation layer on top; 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 manufacturing the electrode site layer, through holes are formed in the second insulating layer at positions corresponding to the electrode sites through patterning.
  • a processing method of a flexible electrode device the flexible electrode device including the flexible electrode for combination with a SEEG electrode as described in the first aspect, the method includes: combining the SEEG The roots of the electrode and the flexible electrode are in contact and fit together in pure water; the fitting angle is adjusted to slowly pull the combination of the SEEG electrode and the flexible electrode out of the water; and the combination is baked to strengthen the relationship between the SEEG electrode and the flexible electrode. of adhesion.
  • the flexible film can be firmly attached to the SEEG electrode without using any adhesive and without affecting the size, physical and chemical properties and surgical process of the SEEG electrode, thereby providing a better connection between the SEEG electrode and the SEEG electrode.
  • Various flexible films provide a basis for surgical implantation, which expands the application scope of SEEG electrodes. For example, when paired with flexible electrodes, it can have functions such as multi-channel, single-cell-level precise EEG signal collection and electrical stimulation.
  • FIG. 1 is an exploded schematic diagram showing a flexible electrode according to an embodiment of the present disclosure.
  • FIG. 2 is a schematic diagram showing different views of a flexible electrode device combined with a SEEG electrode according to an embodiment of the present disclosure.
  • FIG. 3 is a schematic diagram illustrating an end of a flexible electrode device combined with a SEEG electrode according to an embodiment of the present disclosure.
  • Figure 4 is another schematic diagram illustrating a flexible electrode device combined with a SEEG electrode according to an embodiment of the present disclosure.
  • FIG. 5 is a flowchart illustrating a method of manufacturing a flexible electrode according to an embodiment of the present disclosure.
  • FIG. 6 is a schematic diagram illustrating a method of manufacturing a flexible electrode according to an embodiment of the present disclosure.
  • Figure 7 is a schematic diagram illustrating a method of attaching a flexible electrode to a SEEG electrode according to an embodiment of the present disclosure.
  • Figure 8 is a flowchart illustrating a method of attaching a flexible electrode to a SEEG electrode according to an embodiment of the present disclosure.
  • SEEG field potential signal
  • SEEG electrodes have a relatively single function and are often used to locate epileptic lesions. They lack scalability in other functions.
  • Flexible electrodes can be used in combination with flexible electrodes. Record action potential (spike) data to improve the precision and accuracy of epileptic focus location, and can also provide other medical or scientific research uses.
  • the technical solution of the present disclosure mainly relates to a flexible electrode for brain electrical stimulation and electrical signal collection, which has technical effects such as smaller size, better adhesion, and multi-channel, and the flexible electrode is Combined with SEEG electrodes to be implanted into the brain, it can obtain expanded comprehensive detection results, such as achieving multi-channel, single-cell-level accurate EEG signal collection and electrical stimulation, and physiological signal monitoring (ion concentration, pH value, etc.) wait.
  • Figure 1 shows an exploded view of a flexible electrode according to an embodiment of the present disclosure.
  • the shape of the flexible electrode can be strip-shaped, which includes the wire part connected to the external circuit, the electrode site, the attachment part (back end part) attached to the SEEG electrode, and the contact with biological tissue. Partially etc.
  • the actual shape and/or individual components of the electrode can be designed according to requirements and are not limited to the shape and size relationships shown.
  • the flexible electrode has a multi-layer structure, specifically including a flexible separation layer 110, a first insulating layer 120, a circuit board connection layer 130, a conductor layer 140, and a second insulating layer. 150. Electrode site layer 160 and so on.
  • the layer distribution of the flexible electrode shown in Figure 1 is only a non-limiting example, and the flexible electrode in the present disclosure may omit one or more of the layers, and may also include more other layers.
  • the wires in the flexible electrode include a plurality of wires located in the wire layer and spaced apart from each other, wherein the electrode sites in the flexible electrode include respective connections with the plurality of wires through corresponding through holes in the bottom insulating layer.
  • Flexible 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 flexible 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 flexible electrode may include a first insulating layer 120 at the bottom of the electrode and a second insulating layer 150 at the top of the electrode.
  • 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 120 and 150 may include polyimide (PI), polydimethylsiloxane (PDMS), parylene (Parylene), epoxy resin, Polyamide-imide (PAI), etc.
  • the insulating layers 120, 150 are a major portion of the flexible electrode that provide strength.
  • the thickness of the insulating layers 120, 150 may be 100 nm to 300 ⁇ m, preferably 300 nm to 3 ⁇ m, more preferably 1 ⁇ m to 2 ⁇ m, 500 nm to 1 ⁇ m, or the like.
  • each flexible electrode may include one or more wires located in the same wire layer 140 .
  • the conductive wire layer 140 of the flexible electrode includes a plurality of conductive wires, wherein each conductive 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 3 ⁇ 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 140 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 wire's properties such as adhesion, ductility, and conductivity.
  • the wire layer 140 may include a superimposed conductive layer and an adhesion layer, wherein the adhesion layer in contact with the insulating layer 120 and/or 150 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 it 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 flexible electrode may also include electrode sites in the electrode site layer 160 located above the first insulating layer 120. 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 160 may be electrically coupled to corresponding wires through through holes in the first insulating layer 120 at positions corresponding to the electrode sites.
  • the flexible electrode may correspondingly include a plurality of electrode sites in the electrode site layer 160 , and the electrode sites are each connected to a plurality of electrode sites through corresponding through holes in the first insulating layer 120 .
  • One of the conductors is electrically coupled.
  • each electrode site may have a corresponding conductor in conductor layer 140 .
  • 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 160 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 140 among the plurality of layers may be a material that can enhance the adhesion between the electrode site and the wire.
  • the electrode site layer 160 may be a metal film including two superimposed layers, wherein the first layer close to the wire layer 140 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 flexible electrode may further include a bottom electrode site layer (not shown) located under the first insulating layer 120, which electrode site may be in contact with biological tissue after the flexible electrode is implanted. Collect or apply electrical signals directly.
  • the bottom electrode site layer is similar to the electrode sites in the electrode site layer 160.
  • the electrode sites in the bottom electrode site layer can be connected to the electrode site through the bottom insulating layer corresponding to the electrode site. The vias at the locations electrically couple to the 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 160 on both sides of the top and bottom of the flexible electrode, and at opposite positions to the electrode sites in the electrode site layer 160
  • the electrode sites in the electrode site layer 160 are electrically coupled to the same conductor in the conductor layer 140 .
  • the electrode sites in the bottom electrode site layer may also be located at different positions on the top and bottom sides of the flexible electrode from the electrode sites in the electrode site layer 160, so as to be in the biological tissue. Different regions collect or apply electrical signals; and in embodiments according to the present disclosure, electrode sites in the bottom electrode site layer may also be electrically coupled to electrode sites in the conductor layer 140 and in the electrode site layer 160 Different wires.
  • the flexible electrode may further include a flexible separation layer 110 .
  • the flexible separation layer 110 is mainly used in the manufacturing process of flexible electrodes.
  • the flexible separation layer can be removed by a specific substance to separate parts of the flexible electrode and avoid damage to the flexible electrode, and is provided with an adhesion layer.
  • the material of the flexible separation layer is any one of nickel, chromium, aluminum or a combination thereof.
  • the flexible separation layer 110 is also provided with an adhesion layer, the material of which includes chromium, tantalum, tantalum nitride, titanium or titanium nitride.
  • the bottom electrode site layer is an optional but not essential part of the flexible electrode.
  • the flexible electrode may only include the electrode site layer 160 without including the 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 flexible electrode may include at least one rear end site, and the attachment portions of the flexible electrode attached to the optical device each extend from the rear end portion, and the rear end site may pass through the first
  • the via hole in the insulating layer 120 and/or the second insulating layer 150 is electrically coupled to one of the conductors and the back-end circuit to achieve bidirectional signal transmission between the electrode site electrically coupled to the conductor and the back-end circuit.
  • the back-end circuit may refer to the circuit at the back end of the flexible electrode, such as a recording circuit, a processing 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 flexible electrode can also be integrated with the back-end circuit.
  • pre-processing functions such as signal amplification and filtering can be integrated on a dedicated chip, and then integrated with the flexible electrode through bonding or other methods.
  • the integrated PCB at the back end is connected and packaged to achieve wireless transmission and charging.
  • independent flexible electrodes and independent special-purpose chips as back-end circuits can be used, and the electrical connection between the flexible electrodes and the special-purpose chips can be made through ball mounting patches or ACF Bonding; it can also be used as a back-end circuit.
  • a certain space is reserved on the pre-striped wafer of the terminal circuit chip, and the electrodes are directly produced on this basis, so that joint processing or separate processing of the chip and electrode can be realized to achieve a higher level of integration.
  • the backend sites can have planar dimensions on the micron scale and thicknesses on the nanoscale.
  • the back-end site may be a BGA package site with a diameter of 50 ⁇ m to 2000 ⁇ m, or may be a circular, oval, rectangular, rounded rectangle, or chamfered rectangular site with a side length of 50 ⁇ m to 2000 ⁇ m. 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 140 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 conductive layer 140 mentioned above.
  • the metal material is a metal material, and the outermost layer among the multiple layers that may be exposed through the insulating layers 120 and 150 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 wire layer 140 may be nanometer-scale layered to improve the connection between the back-end site layer and the wire.
  • the adhesion layer as the middle layer of 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 flexible 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 flexible 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 site of the flexible electrode and the rear end site for transfer in the rear end portion can both be parts in the conductor layer and be electrically coupled to the corresponding conductor in the conductor 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. 2 is a schematic diagram showing the device after the flexible electrode and the SEEG electrode of the present disclosure are combined from different viewing angles, wherein (A) to (C) respectively show the device after the flexible electrode and the SEEG electrode are combined from the upper side, the side and the top surface. status.
  • the SEEG electrode 201 is generally in a long cylindrical shape, and the flexible electrode 202 is attached to the cylindrical outer wall of the SEEG electrode 201.
  • the inner diameter of the SEEG electrode is usually 0.5 mm to 2 mm, and preferably the inner diameter of the electrode shown in the figure is 1 mm.
  • the commonly used thickness of flexible electrodes is 300nm-10 ⁇ m, and the thickness shown in the picture is 10 ⁇ m; the commonly used width is 100 ⁇ m-500 ⁇ m, and the specific width can be adjusted according to the usage scenario and function.
  • tight adhesion to the SEEG electrode can be achieved without the use of adhesives, which will be described later. Therefore, the flexible electrode itself has the characteristics of ultra-thin, ultra-flexible and good adhesion, and the size and position relationship of the flexible electrode compared to the SSEG electrode can be adjusted in practical applications. Therefore, it is easy to combine the flexible electrode with the SEEG electrode. Can significantly affect the size (such as cross-sectional area), physicochemical properties and/or implantation procedure of the SEEG electrode.
  • the device after the above-mentioned flexible electrode and SEEG electrode are combined is further shown in Figure 3, in which (A) in Figure 3 shows a front schematic view of the device, and (B) in Figure 3 is the area 300 (in (A)) (i.e., an enlarged schematic diagram of the end of the device).
  • the SEEG electrode site 301 is made of a metallic material, such as any one of platinum-iridium alloy, platinum, silver, stainless steel, or a combination thereof.
  • the SEEG electrode posts 302 between them are generally made of insulating material.
  • the electrode site of the flexible electrode 303 is partially attached to the outer wall of the electrode post 302, forming a relatively tightly attached combination.
  • FIG. 4 is another schematic diagram illustrating a flexible electrode device combined with a SEEG electrode according to an embodiment of the present disclosure. That is, in addition to the adhesiveness of the flexible electrode itself, the flexible electrode can also be connected mechanically.
  • the structure of the SEEG electrode 400 can be customized so that the SEEG electrode site 402 (usually a metal ring structure) or the post material forms a gap for the flexible electrode 401 to pass through.
  • Figure 4 (A) and (B) respectively show the customized metal ring of the electrode site 401 and its enlarged schematic diagram. It should be noted that the gap in Figure 4 (B) is only schematic, and the gap in actual application The dimensional relationship between size and SSEG electrode diameter is not the same.
  • a tight connection between the flexible electrode and the SEEG electrode is formed through heat shrinkage or thermal expansion.
  • a groove suitable for the shape of the flexible electrode 401 can be customized on the structure of the SEEG electrode 400, thereby fixing the flexible electrode 401 in the groove, so that the flexible electrode 401 is in contact with the SEEG electrode 400 during the implantation process. No undesired relative movements can occur.
  • method 5000 may include: at S501, manufacturing a flexible separation layer on the substrate; at S502, manufacturing a first insulating layer, a conductor layer, a second insulating 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 S503, the flexible separation layer is removed to separate from the substrate Flexible electrodes.
  • FIG. 6 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. 6 .
  • View (A) of Figure 6 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 6 shows 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 6 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 6 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 6 illustrate the fabrication of the top insulating layer.
  • patterning can generally be achieved directly through patterned exposure and development.
  • patterning cannot be achieved through exposure and development of the insulating layer. Therefore, it can be patterned on top of this layer. Create a thick enough patterned anti-etching layer, and then remove the film in the areas not covered by the anti-etching layer by dry etching (the anti-etching layer will also become thinner, so the anti-etching layer needs to be ensured Thick enough), and then remove the etching resist layer to achieve patterning of the non-photosensitive layer.
  • the insulating layer may be manufactured using photoresist as an etching-resistant layer.
  • the manufacturing of the top insulating layer may include film forming processes, film forming and curing, patterning, enhanced curing and other steps.
  • View (H) shows the structure obtained after the top insulating layer is formed
  • view (I) shows the structure obtained after the top insulating layer is formed.
  • Photoresist and mask are applied on the top insulating layer after film formation.
  • View (J) shows the structure including the etching resist layer obtained after exposure and development.
  • View (K) shows the structure including the prepared The structure of the top insulation layer.
  • the film-forming process, film-forming curing and enhanced curing have been described in detail above for the bottom insulation layer, and are omitted here for the sake of brevity.
  • the patterning step can be performed after film formation and curing, or after enhanced curing. After enhanced curing, the insulating layer has stronger etching resistance.
  • a sufficiently thick layer of photoresist is created on the insulating layer through steps such as glue spreading and baking.
  • the pattern of the top insulating layer shown in FIG. 1 can be realized by arranging the pattern of the mask in relation to the top insulating layer, that is, on one or more conductors of the respective electrode wires extending from the rear end portion.
  • the pattern is transferred to the photoresist on the insulating layer through steps such as exposure and development to obtain an etching-resistant layer, in which the portion that needs to be removed from the top insulating layer is exposed.
  • the exposed portions of the top insulating layer may be removed by oxygen plasma etching to obtain the structure shown in view (K).
  • 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 6 shows the fabrication of the top electrode site layer over the top insulating layer.
  • Van der Waals force If the distance between the two materials is small enough, van der Waals force or hydrogen bonding will occur between the molecules, thereby obtaining good adhesion.
  • the SEEG electrode post material and the flexible film material are both non-polar materials. , it is easy to form such molecular forces.
  • the foregoing embodiments respectively illustrate the common manifestations of the above-mentioned forces.
  • the devices in Figures 2 and 3 mainly show examples of flexible electrodes attached to the surface of SEEG electrodes, which achieve the connection between the flexible electrodes and the SEEG electrodes without using adhesives and without relying on the constraints of mechanical structures. Attach.
  • the device in Figure 4 shows another example of using mechanical structures to assist electrode attachment, where a gap is created by customizing the structure of the SEEG electrode for the flexible electrode to pass through.
  • the method of attaching the flexible electrode to the SEEG electrode requires at least pure water (distilled water and above), an open container that can be used to hold water (including but not limited to beakers, Petri dishes, etc.), guide flexible
  • the tools required for the film including but not limited to thin tungsten wires, toothpicks, syringe needles, etc.
  • auxiliary implementation tools such as ovens and high-temperature-resistant containers (including but not limited to glass petri dishes, enamel cylinders, etc.).
  • FIG. 7 shows the SEEG electrode 701 and the flexible electrode 702 performing the attachment operation.
  • (A) and (B) of FIG. 7 respectively show the air 703 and the liquid (such as pure water) at different viewing angles. 704 and the dividing line between them.
  • the roots of the flexible electrodes 702 of the SEEG electrodes 701 are in contact with and attached to each other in pure water.
  • the assembly is slowly pulled out of the water in the direction indicated by the arrow in Figure 7 .
  • the remaining parts of the flexible electrode 702 will be sequentially attached to the surface of the SEEG electrode 701 under the surface tension of the water, so that the end of the flexible electrode 702 is finally placed on the non-metallic part of the SEEG electrode 701.
  • the device is baked to enhance the adhesion between the SEEG electrode 701 and the flexible electrode 702 .
  • the device combined with the SEEG electrode 701 and the flexible electrode 702 is placed in a high-temperature resistant container and placed in an oven.
  • the high-temperature resistant container should have a lid to prevent air flow interference in the oven.
  • the oven baking temperature and time depend on the high temperature resistance of the flexible electrode 702 and the SEEG electrode 701. It is generally believed that the temperature should be above 40°C, preferably 60°C to 200°C, and the baking time should be above 3 minutes.
  • the most advantageous technical effect of the technical solution of the present application is to achieve flexible electrode attachment to the SEEG electrode without the need for adhesives.
  • it can also be attached through various adhesives including biodegradable materials.
  • the agent is attached to the SEEG electrode, in which biodegradable materials such as polyethylene glycol, polylactic acid, polylactic acid-glycolic acid copolymer, silk protein, etc.
  • FIG 8 is a flowchart illustrating a method of attaching a flexible electrode to a SEEG electrode according to the aforementioned embodiment. Specifically, in step S801, the SEEG electrode and the root of the flexible electrode are contacted and bonded in pure water. Then in step S802, the fitting angle is adjusted, and the combination of the SEEG electrode and the flexible electrode is slowly pulled out of the water. Finally, at step S803, the combination is baked to enhance the adhesion between the SEEG electrode and the flexible electrode.
  • the flexible electrodes of the present disclosure may be used in conjunction with DBS electrodes or attached to optical components.
  • 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SEEG电极结合的柔性电极装置，包括：可植入且柔性的至少一个电极丝，其中每个电极丝分别包括：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，其中至少一个电极丝被配置为附接到SEEG电极，并且在SEEG电极被植入后与生物组织接触。

Description

用于与SEEG电极结合的柔性电极装置及其制造方法 技术领域
本公开涉及用于与立体定向脑电图(SEEG)电极结合的柔性电极装置及其制造方法，并且具体地，涉及可以在不使用特定胶黏剂且不明显影响SEEG电极的情况下实现牢固贴附的柔性电极装置及其制造方法。
背景技术
对于药物难治性癫痫患者而言，及时正确诊断有利于不同级别医生和癫痫专科医生为病人提供更为有效的治疗和服务。SEEG技术运用微创的方法，无需手术切口，仅需头皮和颅骨2mm钻微孔，将深部电极放入脑深部特定的位置。因此，该技术适用于需要颅内电极脑电图定位的癫痫患者。
SEEG技术把定位方法从2D引入3D层面，可以直接放置至额叶深部、大脑内侧面、扣带回、颞叶内侧等常规皮层电极无法达到颅内任何靶向部位，对大脑进行全方位立体覆盖，从而到达准确定位病灶、提高治疗效果的目的，是一种全新的癫痫病灶定位技术，对于明确癫痫患者病灶有着重要作用。
发明内容
本申请提出了一种用于与SEEG电极结合的柔性电极装置及其制造方法。
根据本公开的实施例的第一方面，提供了一种用于与SEEG电极结合的柔性电极装置，包括：可植入且柔性的至少一个电极丝，其中每个电极丝分别包括：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，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，其中该至少一个电极丝被配置为附接到SEEG电极，并且在SEEG电极被植入后与生物组织接触。
根据本公开的实施例的第二方面，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所述的用于与SEEG电极结合的柔性电极，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三方面，提供了一种柔性电极装置的处理方法，该柔性电极 装置包括如第一方面所述的用于与SEEG电极结合的柔性电极，该方法包括：将SEEG电极与柔性电极的根部在纯水中接触并贴合；调整贴合角度，将SEEG电极与柔性电极的组合缓缓拉出水面；以及将该组合进行烘烤以增强SEEG电极与柔性电极之间的粘附力。
根据本公开的实施例的优点在于可以在不使用任何胶黏剂且不影响SEEG电极的尺寸、物化性质和手术过程的前提下，实现柔性薄膜与SEEG电极的牢固贴附，从而为SEEG电极与各种柔性薄膜共同进行手术植入提供基础，拓展了SEEG电极的应用面，诸如与柔性电极的搭配可使具备多通道、单细胞级精确脑电信号采集及电刺激等功能。
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的分解示意图。
图2是示出了根据本公开的实施例的与SEEG电极结合的柔性电极装置的不同视角示意图。
图3是示出了根据本公开的实施例的与SEEG电极结合的柔性电极装置的端部的示意图。
图4是示出了根据本公开的实施例的与SEEG电极结合的柔性电极装置的另一示意图。
图5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6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7是示出了根据本公开的实施例的将柔性电极附接到SEEG电极的方法的示意图。
图8是示出了根据本公开的实施例的将柔性电极附接到SEEG电极的方法的流程图。
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。
本申请的发明人在研究中发现，现有的SEEG技术受制于体积、通道数和电极位点大小，即使能用于确定癫痫病灶位置，但无法进行单细胞级的精确脑电数据采集、电刺激及脑内微环境的监控。具体而言，单独的SEEG电极受制于体积和原始设计，通道数一般为十余个，电极位点较大，为毫米尺度，因此通道数较少且通道信息量庞杂，记录精度较低，通常得到的数据为场电位信号(LFP)，无法胜任单细胞级脑电信号采集；SEEG电极功能较为单一，常用于癫痫病灶定位，在其他功能方面缺乏拓展性，与柔性电极组合使用可以借助柔性电极记录动作电位(spike)数据，提高癫痫病灶定位精度和准确性，也可提供其他医疗或科研用途。
基于此，本申请的技术方案尝试将超薄超柔性的薄膜电极贴附到SEEG电极上以改善、拓展SEEG电极的功能。
概括而言，本公开的技术方案主要涉及一种用于脑部电刺激和电信号收集的柔性电极，其具备尺寸更小、贴附性更好以及多通道等技术效果，并将该柔性电极结合到SEEG电极上以配合植入到脑区，从而获得拓展性的综合检测结果，诸如实现多通道、单细胞级精确脑电信号采集及电刺激，生理信号监测(离子浓度、pH值等)等。
图1示出了根据本公开的实施例的柔性电极的分解图。如图1所示，柔性电极的外形可以是条状的，其中包括连接到外部电路的导线部分、电极位点、贴附到SEEG电极的贴附部分(后端部分)以及与生物组织的接触部分等。需要注意的是，该电极的实际形状以及/或者单个组成部分均可以根据需求进行设计，而并不限于已示出的形状和尺寸关系。具体地，从图中可以清楚地看出，柔性电极为多层结构，具体而言，包括柔性分离层110、第一绝缘层120、与线路板连接层130、导线层140、第二绝缘层150、电极位点层160等。应理解的是，图1中示出的柔性电极的各层分布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，柔性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，柔性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。柔性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中示出的柔性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，柔性电极可以包括位于电极底部的第一绝缘层120和位于电极顶部的第二绝缘层150。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120、150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)等。此外，绝缘层120、150还是柔性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120、150的厚度可以为100nm至300μm，优选地为300nm至3μm，更优选地为1μm至2μm、500nm至1μm等。
柔性电极中的导线层分布在第一绝缘层120和第二绝缘层150之间的导线层140中。在根据本公开的实施例中，每个柔性电极可以包括位于同一导线层140中的一个或多个导线。例如，从图1中可以清楚地看出，柔性电极的导线层140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3μm。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140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140可以包括叠加的导电层和粘附层，其中，与绝缘层120和/或150接触的粘附层为钛(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，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。
柔性电极还可以包括位于第一绝缘层120之上的电极位点层160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。在柔性电极中，电极位点层160中的电极位点可以通过第一绝缘层120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电极位点层160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120中的相应通孔与多个导线之一电耦合。
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140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160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140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160可以是包括叠加的两个分层的金属薄膜，其中，接近导线层140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，柔性电极还可以包括位于第一绝缘层120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160中的电极位点类似，在柔性电极中，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160中的电极位点位于柔性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160中的电极位点电耦合到导线层140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160中的电极位点位于柔性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140中的与电极位点层160中的电极位点不同的导线。
在根据本公开的实施例中，柔性电极还可以包括柔性分离层110。柔性分离层110主要用于柔性电极的制造过程，柔性分离层能够被特定物质去除以分离柔性电极的部分并避免对柔性电极的损伤，并且设置有粘附层。柔性分离层的材料为镍、铬、铝中的任一种或其组合。柔性分离层110还设置有粘附层，其材料包括铬、钽、氮化钽、钛或氮化钛。
应理解的是，底部电极位点层是柔性电极的可选而非必要的一部分，例如图1中所示的分解结构中，柔性电极可以仅包括电极位点层160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，柔性电极的后端部分可以包括至少一个后端位点，柔性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120和/或第二绝缘层150中的通孔电耦合到导线之一和后端电路，以实现与该导线电耦合的电极位点和后端电路之间的双向信号传输。这里，后端电路可以是指在柔性电极后端的电路，诸如与柔性电极的信号相关联的记录电路、处理电路等。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。在根据本公开的实施例中，柔性电极也可以与后端电路集成，具体而言，可以将信号放大和滤波等预处理功能集成在专用芯片上，然后再通过键合等方式与在柔性电极后端的一体化的PCB进行连接和封装，从而实现无线传输和充电等。在这种情况下，可以采用独立的柔性电极和独立的作为后端电路的专用芯片，通过植球贴片或ACF Bonding等方式进行柔性电极和专用芯片之间的电气连接；也可以在作为后端电路的芯片的预先流片好的晶圆上预留出一定空间，在此基础上直接进行电极的制作，从而能够实现芯片和电极的联合 加工或分离加工工艺，达到更高的集成度。
后端位点可以具有微米级的平面尺寸和纳米级的厚度。作为非限制性示例，后端位点可以是直径为50μm至2000μm的BGA封装位点，或者可以是边长为50μm至2000μm的圆形、椭圆形、矩形、圆角矩形、倒角矩形的位点。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140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140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120、150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140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140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，采用的柔性电极具有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，柔性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，柔性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2是以不同视角示出本公开的柔性电极与SEEG电极结合后的装置的示意图，其中(A)至(C)分别从侧上方、侧面以及顶面示出了柔性电极与SEEG电极结合后的状态。在一个非限制性实施例中，如图所示，SEEG电极201大致为长圆柱状外形，柔性电极202贴附在SEEG电极201的柱状外壁上。
如图2所示，SEEG电极内径通常为0.5mm至2mm，优选地以图示电极内径为1mm。柔性电极常用的厚度为300nm-10μm，图中所示厚度为10μm；常用宽度为100μm-500μm， 具体宽度可根据使用情景和功能进行调整。此外，可以在不使用胶黏剂的情况下实现与SEEG电极的紧密贴附，这一点将在稍后进行描述。由此，柔性电极自身具备的超薄超柔性以及贴附性良好等特征，以及可以在实际应用中调整柔性电极相比于SSEG电极的尺寸和位置关系，因而将柔性电极与SEEG电极组合之后不会显著地影响SEEG电极的尺寸(诸如横截面积)、物化性质和/或植入手术过程。
上述柔性电极与SEEG电极结合后的装置进一步如图3所示，其中图3中的(A)示出了该装置的正面示意图，图3中的(B)是(A)中的区域300(即装置端部)的放大示意图。在一个非限制性实施例中，如图所示，SEEG电极位点301由金属材料制成，诸如铂-铱合金、铂金、银、不锈钢中的任一种或其组合，在各电极位点之间的SEEG电极接杆302一般由绝缘材料制成。柔性电极303的电极位点部分地贴附到电极接杆302外侧壁，形成相对紧密贴附的组合。
可替代地，图4是示出了根据本公开的实施例的与SEEG电极结合的柔性电极装置的另一示意图。即，除了基于柔性电极自身贴附性之外，还可以通过机械连接方式将柔性电极。具体而言，如图4所示，可以对SEEG电极400结构进行定制，使SEEG电极位点402(常为金属环结构)或接杆材料形成可供柔性电极401穿过的空隙。图4中(A)和(B)分别示出了定制的电极位点401的金属环及其放大示意图，需要注意的是，图4(B)中的空隙仅为示意性，实际应用中空隙大小与SSEG电极直径之间的尺寸关系并非如此。此外，在柔性电极402穿过电极位点401的金属环空隙后，通过热缩或热胀等方法形成柔性电极与SEEG电极之间的紧固连接。可替代地，可以在SEEG电极400的结构上定制出与柔性电极401外形相适应的凹槽，从而将柔性电极401固定在该凹槽中，使得在植入过程中柔性电极401与SEEG电极400不会发生不期望的相对移动。
图5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5所示，方法5000可以包括：在S501处，在基底之上制造柔性分离层；在S502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S503处，去除柔性分离层以从基底分离出柔性电极。
图6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6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6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6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6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6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140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6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，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6的视图(L)示出了在顶部绝缘层之上制造顶部电极位点层。
接下来，将结合图7描述根据本公开的实施例的将柔性电极附接到SEEG电极的方法。
一般地，将根据本公开的柔性电极贴附到SEEG电极时，两者之间会同时形成多种力，这些力的合力共同造成了紧密贴附、不易剥离的技术效果。这些力包括但不限于以下几种：
(1)机械结合：常见于热熔胶膜与被粘物的粘接力，柔性电极与SEEG电极之间经干燥固化产生的摩擦力形成机械结合力。
(2)范德华力：两种材料靠近距离足够小时，分子间就产生了范德华力或氢键的结合，从而获得良好的粘接力，SEEG电极接杆材料与柔性薄膜材料均为非极性材料，易形成此种分子作用力。
(3)互相扩散：高分子化合物之间的粘接，是由于大分子本身或其链段通过热运动引起的扩散作用，实质上是界面发生了互溶，从而形成了牢固的结合。
(4)电荷引力：来源于双电层中正负电荷之间的吸引力，这种吸引力与电荷密度的平方成正比。
前述实施例分别说明了上述几种力的常见体现形式。图2和图3中的装置主要示出了柔性电极贴附到SEEG电极表面的示例，其在不使用胶黏剂并且不依赖于机械结构的约束的情况下实现柔性电极与SEEG电极之间的贴附。可替代地，图4中的装置示出了使用机械结构辅助电极附接的另一示例，其中通过定制SEEG电极的结构形成可供柔性电极穿过的空隙。
在一个非限制性实施例中，柔性电极贴附到SEEG电极的方式至少需要纯水(蒸馏水及以上级别)、可用于盛水的开口容器(包括但不限于烧杯、培养皿等)、引导柔性薄膜所需的工具(包括但不限于细钨丝、牙签、注射器针头等)以及/或者烘箱和耐高温容器(包括但不限于玻璃培养皿、搪瓷缸等)等辅助实现工具。
实验可知，柔性电极通常为非极性材料，如果电极首先与脑表面或其它物质(诸如水)接触的一端附接在由极性材料制成的金属SEEG电极位点上，则会导致由于结合力不足而容易脱离，因此建议将首先进入脑区的末端结合在由非极性材料制成的SEEG接杆上。
具体而言，图7中示出了进行贴附操作的SEEG电极701与柔性电极702，图7的(A)和(B)分别示出了不同视角下的空气703和液体(诸如纯水)704及其之间的分界线。SEEG电极701的柔性电极702的根部在纯水中接触并贴合，调整好贴附角度后沿着图7中箭头指示的方向将组合体缓缓拉出水面。此时，柔性电极702的剩余部分会在水的表面张 力作用下随着依次贴附于SEEG电极701的表面，使得柔性电极702的端部最终置于SEEG电极701的非金属部分。SEEG电极701与柔性电极702结合后的装置完全提出水面后，将该装置进行烘烤以增强SEEG电极701与柔性电极702之间的粘附力。
在一个非限制性实施例中，将SEEG电极701与柔性电极702结合后的装置放置于耐高温容器中放入烘箱，耐高温容器宜有盖子以防止烘箱中气流干扰。烘箱烘烤温度和时间取决于柔性电极702及SEEG电极701的耐高温能力，一般认为温度应在40℃以上，60℃～200℃为宜，烘烤时间在3分钟以上。
需要注意的是，本申请的技术方案最有利的技术效果在于不需要胶黏剂的情况下实现柔性电极附接到SEEG电极，可替代地，也可以通过包括生物可降解材料等多种胶黏剂贴附到SEEG电极，其中生物可降解材料诸如聚乙二醇、聚乳酸、聚乳酸-羟基乙酸共聚物、蚕丝蛋白等。
图8是示出了根据前述实施例的将柔性电极附接到SEEG电极的方法的流程图。具体地，在步骤S801中，将SEEG电极与柔性电极的根部在纯水中接触并贴合。随后在步骤S802中，调整贴合角度，将SEEG电极与柔性电极的组合缓缓拉出水面。最后，在步骤S803处，将该组合进行烘烤以增强SEEG电极与柔性电极之间的粘附力。
可替代地，本申请的技术方案还可以用于其它应用场景。本公开的柔性电极可以与DBS电极结合使用，或者贴附到光学元件结合使用。
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 (19)

  1. 一种用于与SEEG电极结合的柔性电极装置，包括：
    可植入且柔性的至少一个电极丝，其中所述至少一个电极丝中的每个电极丝分别包括：
    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
    所述至少一个电极丝被配置为附接到SEEG电极，并且在所述SEEG电极被植入后与生物组织接触。
  2. 根据权利要求1所述的柔性电极装置，其中：
    每个电极丝中的导线包括位于所述柔性电极的导线层中并且彼此间隔开的多个导线，以及
    每个电极丝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。
  3. 根据权利要求1所述的柔性电极装置，其中
    后端部分，包括至少一个后端位点，
    其中，所述至少一个电极丝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。
  4. 根据权利要求1所述的柔性电极装置，其中：
    电极丝的厚度在300nm至200μm。
  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，其中，所述柔性分离层能够被特定物质去除以分离柔性电极的部分并避免对柔性电极的损伤。
  6. 根据权利要求5所述的柔性电极装置，其中：
    所述柔性分离层的其中，所述柔性分离层的材料为镍、铬、铝中的任一种或其组合。
  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：
    每个电极丝中的电极位点和导线分别包括导电金属层和粘附层。
  10. 根据权利要求9所述的柔性电极装置，其中：
    所述导电金属层的材料为金、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，并且厚度为5nm至200μm，以及
    所述粘附层的材料包括铬、钽、氮化钽、钛或氮化钛，并且厚度为1至50nm。
  11. 根据权利要求1所述的柔性电极装置，其中：
    所述至少一个电极丝以贴附的形式附接到所述SEEG电极表面。
  12. 根据权利要求1所述的柔性电极装置，其中：
    所述至少一个电极丝通过机械结构附接到所述SEEG电极表面。
  13. 根据权利要求12所述的柔性电极装置，其中：
    所述机械结构包括通过定制所述SEEG电极的结构形成可供柔性电极穿过的空隙。
  14. 根据权利要求1所述的柔性电极装置，其中：
    所述至少一个电极丝通过生物可降解材料贴附到所述SEEG电极表面。
  15. 根据权利要求14所述的柔性电极装置，其中：
    所述生物可降解材料包括聚乙二醇、聚乳酸、聚乳酸-羟基乙酸共聚物、蚕丝蛋白中的任一种或其组合。
  16. 根据权利要求1所述的柔性电极装置，其中：
    所述SEEG电极的材料为铂-铱合金、铂金、银、不锈钢中的任一种或其组合，并且所述SEEG电极内径为0.5mm至2mm。
  17. 一种可植入电极装置，包括：
    SEEG电极以及可植入且柔性的至少一个电极丝，
    其中所述至少一个电极丝中的每个电极丝分别包括：
    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，
    其中所述至少一个电极丝被配置为附接到所述SEEG电极，并且在所述SEEG电极被植入后与生物组织接触。
  18. 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1-16中的任一项所述的用于与SEEG电极结合的柔性电极，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。
  19. 一种柔性电极装置的处理方法，所述柔性电极装置包括如权利要求1-16中的任一项所述的用于与SEEG电极结合的柔性电极，所述方法包括：
    将SEEG电极与所述柔性电极的根部在液体中接触并贴合；
    调整贴合角度，将SEEG电极与所述柔性电极的组合缓缓拉出所述液体的表面；以及
    将该组合进行烘烤以增强SEEG电极与所述柔性电极之间的粘附力。
PCT/CN2022/102151 2022-06-17 2022-06-29 用于与seeg电极结合的柔性电极装置及其制造方法 WO2023240686A1 (zh)

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