Flexible microelectrode array, preparation method thereof and brain-computer interface device

Abstract

The invention discloses a flexible microelectrode array, a preparation method thereof and a brain-computer interface device, and relates to the field of artificial intelligence. Comprising a flexible substrate, a plurality of brain signal metal electrodes, a first metal conductive connection assembly and a second metal conductive connection assembly, and the flexible substrate is provided with a first side and a second side which are oppositely arranged; the plurality of brain signal metal electrodes are arranged on the first side to form an electrode array; the first metal conducting assembly is arranged on the second side of the flexible substrate, is packaged in the flexible substrate, and comprises a plurality of first connecting sites and a plurality of connecting wires; the second metal conducting and connecting assembly comprises a plurality of second connecting sites exposed to the flexible substrate, and the second connecting sites are arranged on the first side or the second side of the flexible substrate; the plurality of first connecting sites are respectively connected with the plurality of brain signal metal electrodes, and are respectively connected with the plurality of second connecting sites through the plurality of connecting wires; and the plurality of second connection sites are used for being in communication connection with a processor.

Description

Technical Field

[0001] The present application relates to the field of artificial intelligence technology, and in particular to a flexible microelectrode array and a preparation method thereof, and a brain-computer interface device. Background Art

[0002] Flexible microelectrode arrays have good flexibility and stretchability, and can better fit with the interface of nerve cells, thereby achieving long-term stable culture of neuronal cells and real-time signal detection, and can also improve the sensitivity and quality of neuroelectrophysiological signal detection. Flexible microelectrode arrays can be used in the field of neuroscience to study brain function and nervous system diseases. By recording the electrical activity of different brain regions, the functional state and pathological changes of the brain can be understood. It can also be used in the study of brain-computer interfaces to help achieve direct communication between the human brain and computers or other devices.

[0003] Currently, the flexible electrode structure used in the cerebral cortex is generally a flat thin-film brain signal metal electrode with a certain height. In the long-term implantation environment in the brain, there are problems such as multiple packaging times, large implantation wounds, and great damage to the human body. Summary of the invention

[0004] The present application provides a flexible microelectrode array for brain-computer interface and a preparation method thereof, as well as a brain-computer interface device, to solve the problems of multiple packaging times, large implantation wounds, and great damage to the human body.

[0005] In a first aspect, the present application provides a flexible microelectrode array for a brain-computer interface, comprising:

[0006] A flexible substrate having a first side and a second side disposed opposite to each other;

[0007] A plurality of metal electrodes for brain signals are disposed on the first side and spaced apart to form an electrode array;

[0008] a first metal conductive component, disposed on the second side of the flexible substrate and encapsulated in the flexible substrate, comprising a plurality of first connection sites and a plurality of connection wires; and

[0009] A second metal conductive component includes a plurality of second connection sites exposed to the flexible substrate, wherein the second connection sites are arranged on the first side or the second side of the flexible substrate;

[0010] Wherein, a plurality of the first connection sites are respectively connected to a plurality of the brain signal metal electrodes, and are respectively connected to a plurality of the second connection sites through a plurality of connecting wires;

[0011] The plurality of second connection sites are used for communication connection with the processor.

[0012] In the present application, when the flexible microelectrode array is implanted in the brain, the brain signal metal electrode contacts the nerves of the brain, and the first metal conductive component is connected to the brain signal metal electrode to transmit the brain signal received by the brain signal metal electrode to the second metal conductive component, and the second metal conductive component transmits the signal to the processor through the connection site to achieve control or response. Since the plurality of the first connection sites are respectively connected to the plurality of the brain signal metal electrodes, and are respectively connected to the plurality of second connection sites through a plurality of connecting wires, the plurality of first connection sites and the plurality of connecting wires are encapsulated in the flexible substrate, so there is no need to additionally set up leads connecting the first connection sites to the second connection sites, and the signals of the first connection sites and the second connection sites are directly connected through patterned connecting wires. Since the second connection site is exposed, it can be directly welded to the solder joint array of the processor. After welding, it is only necessary to integrate the processor and the electrode array to achieve the packaging and protection of the entire flexible microelectrode array, without the need to encapsulate the leads connecting the first connection site to the second connection site once more, and there is no need to lead out the leads, which reduces the volume of the flexible microelectrode array, makes the implantation wound smaller, and causes less damage to the brain tissue.

[0013] It should be noted that there are two forms of the second connection sites being arranged on the first side or the second side of the flexible substrate. One is that all the second connection sites are arranged on the second side of the flexible substrate; the other is that all the second connection sites are arranged on the first side of the flexible substrate.

[0014] The first metal conducting component is encapsulated in the insulating layer on the second side of the flexible substrate, which can fix and protect the electrode, reduce the movement of the electrode, and reduce the damage to the brain tissue. The second metal conducting component is exposed outside the insulating layer on the first side or the second side of the flexible substrate, and can be directly welded to the solder joint array of the processor without the need to lead out additional leads from the electrode array and perform secondary encapsulation on the leads. Without the need for complex wire settings, large-area wire laying, or large implantation wounds, good signal conduction can be achieved.

[0015] It should be noted that, in some embodiments, the brain signal metal electrode can adopt a raised tip electrode structure design, which improves the mechanical strength of the electrode, improves the mechanical properties and ductility of long-term implantation, and meets the needs of long-term implantation. The flexible tip electrode array is easier to adapt to the curved surface of the cerebral cortex, reduces displacement and sliding in a long-term implantation environment, and makes signal transmission more accurate. In order to improve the biocompatibility of the flexible microelectrode array, a plurality of protrusions containing mounting channels can be set on the first side of the flexible substrate, and the brain signal metal electrodes can be placed in the mounting channels of the protrusions respectively, with the tip exposed, thereby increasing the pressure on the tip during implantation, reducing implantation resistance, and at the same time improving the accuracy of signal transmission and reducing the damage of hard metal materials to brain tissue.

[0016] The present application does not limit the shape of the flexible microelectrode array, which may be circular, square, triangular, diamond or polygonal.

[0017] In some embodiments, the second metal conductive component is arranged on the peripheral side of the first metal conductive component. Since the first metal conductive component is encapsulated in the insulating layer on the second side of the flexible substrate and is respectively connected to the plurality of brain signal metal electrodes, and the second metal conductive component is exposed outside the insulating layer on the second side of the flexible substrate for connection with the processor, in order to reduce the interference of the second metal conductive component on the first metal conductive component, the second metal conductive component is arranged on the peripheral side of the first metal conductive component, so that the first metal conductive component is located in the middle position and the second metal conductive component is located at the edge position, which can also reduce the wiring distance of the second metal conductive component and facilitate connection with the processor.

[0018] In some embodiments, the material of the flexible substrate includes at least one of polydimethylsiloxane, polymethyl methacrylate, polyimide, p-xylene polymer and silicone, which is a material with good biocompatibility, thereby reducing the risk of rejection reaction; and / or,

[0019] The material of the brain signal metal electrode includes at least one of gold, silver, copper and platinum. The brain signal metal electrode has good mechanical strength and ductility, meeting the needs of long-term implantation. Using at least one of the above materials can improve the stability of the brain signal metal electrode and reduce the harm of electrode corrosion to the human body.

[0020] In some embodiments, the number of the brain signal metal electrodes is 8 to 64. The electrode array formed by 8 to 64 brain signal metal electrodes is usually a low-flux electrode array, with a small amount of signal and low transmission resistance. The integrated packaging form can realize direct data transmission and reduce the transmission pressure caused by excessive data volume.

[0021] The shapes of the first connection site and the second connection site include, but are not limited to, square, circle, triangle, rhombus, trapezoid or polygon. The second connection site can be distributed at equal intervals or non-equal intervals, and can be arranged only on one side of the flexible microelectrode array, on two opposite or adjacent sides, or on all sides.

[0022] It should be noted that the position and number of the first connection sites correspond one-to-one to the brain signal metal electrodes, and the number of the second connection sites corresponds to the number of the first connection sites, that is, each brain signal metal electrode is connected to a first connection site, and each first connection site is connected to a second connection site through a connecting wire, thereby realizing the transmission of the signal of each brain signal metal electrode to the processor, and the signals of each electrode do not interfere with each other and are transmitted independently.

[0023] It should be noted that the thickness of the flexible substrate can be 10 to 70 μm. The total height of the brain signal metal electrode can be 0.5 to 2 mm, the exposed height can be 0.1 to 0.5 mm, and the diameter can be 0.1 to 1.5 mm. The shape of the protrusion can be cylindrical or conical. In order to improve implantation efficiency and reduce implantation resistance, the shape of the protrusion is usually conical.

[0024] In a second aspect, the present application provides a method for preparing a flexible microelectrode array, comprising the following steps:

[0025] A flexible substrate having a plurality of protrusions arranged at intervals on one side is prepared;

[0026] A metal conductive layer including a plurality of connection sites and connection wires is prepared on a side of the flexible substrate without protrusions;

[0027] A flexible substrate material is used to encapsulate the connection sites and connection wires of a part of the metal conductive layer to form a plurality of first connection sites and a plurality of connection wires of a first metal conductive component, and another part of the connection sites of the metal conductive layer is exposed to form a plurality of second connection sites of a second metal conductive component;

[0028] A brain signal metal electrode installation channel is formed on the protrusion of the flexible substrate, and a brain signal metal electrode is prepared in the installation channel and connected to the first metal conducting component to obtain a flexible microelectrode array.

[0029] By preparing a metal conductive layer containing multiple connection sites and connecting wires on the side of the flexible substrate without protrusions, and using insulating materials to encapsulate and wrap part of the connection sites of the metal conductive layer to form a first metal conductive component, and exposing another part of the connection sites of the metal conductive layer to form a second metal conductive component, the reliability of the communication connection between the first metal conductive component and the second metal conductive component can be achieved, and the molding of the two metal conductive components can be achieved in one molding. By forming a brain signal metal electrode installation channel on the protrusion of the flexible substrate, preparing a brain signal metal electrode in the installation channel, and connecting it to the first metal conductive component, a flexible microelectrode array can be obtained. The number and size of electrodes can be customized according to the requirements of specific application scenarios, and the electrode shape suitable for different brain regions can be designed, which is more flexible and changeable. By patterning during the preparation of the metal conducting layer, a plurality of first connection sites and a plurality of connection wires of the first metal conducting component and a plurality of second connection sites of the second metal conducting component can be formed at one time. By encapsulating the plurality of first connection sites and the plurality of connection wires through a flexible substrate material, a reliable connection between the first connection site and the second connection site can be achieved. There is no need to lead out additional leads from the first connection site, and there is no need to encapsulate the leads additionally. The structure is simple, and data transmission is direct and real.

[0030] The insulating layer material includes, but is not limited to, PDMS (polydimethylsiloxane), PMMA (polymethyl methacrylate), PI (polyimide), Parylene-C (paraxylene polymer) and silicone, which are flexible materials with good biocompatibility. The material of this layer is selected to be consistent with the material of the flexible substrate layer to further improve flexibility and compatibility. The method of forming the insulating layer includes, but is not limited to, thin film deposition process (CVD, PVD), spin coating process, template casting process, electrochemical deposition process, etc.

[0031] In some embodiments, preparing a flexible substrate having a plurality of protrusions spaced apart on one side includes:

[0032] preparing a flexible mold layer on a substrate;

[0033] cutting a plurality of tapered holes arranged at intervals in the flexible mold layer;

[0034] A flexible substrate having a plurality of protrusions arranged at intervals is prepared on the side of the flexible mold layer having the tapered holes.

[0035] By cutting a plurality of tapered holes at intervals on the flexible mold layer, a flexible substrate containing a plurality of protrusions at intervals is prepared on the side of the flexible mold layer containing the tapered holes. The flexible substrate containing a plurality of protrusions at intervals can be prepared by means of a mold. The shape of the flexible substrate can be changed by changing the shape of the mold, which is more flexible and simple. The flexible mold layer and the substrate can be removed by demolding later. The substrate can be a hard substrate including but not limited to a silicon wafer and a quartz wafer, which improves the supporting force of the flexible substrate during preparation and reduces deformation. The flexible substrate containing a plurality of protrusions at intervals can be prepared by thin film deposition processes (CVD, PVD), template casting processes, and electrochemical deposition processes to form the flexible substrate.

[0036] In some embodiments, the step of preparing a metal conductive layer including a plurality of connection sites and connection wires on a side of the flexible substrate without protrusions comprises:

[0037] Spin coating photoresist on a flexible substrate and obtaining a photoresist mask;

[0038] A metal layer is prepared under the cover of a photoresist mask, and the photoresist is removed to obtain a metal conductive layer containing multiple connection sites and connection wires.

[0039] Since the metal conductive layer is not a flat plane, but forms different conductive layer patterns according to the positions of the brain signal metal electrodes and the wires connecting the multiple brain signal metal electrodes, in order to prepare a metal conductive layer with a specific pattern, the photoresist mask is used to cover it. After the metal layer is prepared, the photoresist is removed to obtain a metal conductive layer containing multiple connection sites and connecting wires. The photoresist can be a positive photoresist or a negative photoresist. The positive photoresist is cured by light, and the negative photoresist is dissolved by light. The method for preparing the metal layer includes but is not limited to thin film deposition processes (CVD, PVD, evaporation), template casting processes, electrochemical deposition processes, electroplating processes, machining and other processes.

[0040] In some embodiments, a brain signal metal electrode installation channel is formed on the protrusion of the flexible substrate, a brain signal metal electrode is prepared in the installation channel, and connected to the first metal conducting component to obtain a flexible microelectrode array:

[0041] The method of forming the brain signal metal electrode installation channel includes laser cutting or dry etching. By forming the brain signal metal electrode installation channel in the flexible mold layer by laser cutting or dry etching, the number, shape and position of the brain signal metal electrodes can be better controlled; and / or,

[0042] The method for preparing brain signal metal electrodes includes any one of electrochemical deposition, capillary effect and metal welding. By using electrochemical deposition, capillary effect and metal welding to prepare brain signal metal electrodes, the preparation amount of the metal electrode can be controlled to achieve the desired effect.

[0043] In some embodiments, the material of the flexible substrate includes at least one of polydimethylsiloxane, polymethyl methacrylate, polyimide, p-xylene polymer and silicone, which is a material with good biocompatibility, thereby reducing the risk of rejection reaction; and / or,

[0044] The material of the brain signal metal electrode includes at least one of gold, silver, copper and platinum. The brain signal metal electrode has good mechanical strength and ductility, meeting the needs of long-term implantation. Using at least one of the above materials can improve the stability of the brain signal metal electrode and reduce the harm of electrode corrosion to the human body.

[0045] In a third aspect, the present application proposes a brain-computer interface device, comprising the flexible microelectrode array of the first aspect of the present application. BRIEF DESCRIPTION OF THE DRAWINGS

[0046] In order to more clearly illustrate the technical solutions in the embodiments of the present application, the drawings required for use in the description of the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0047] Figure 1 This is a schematic diagram of the flexible microelectrode array structure according to an embodiment of the present application.

[0048] Figure 2 This is a bottom view of a flexible microelectrode array structure according to an embodiment of the present application.

[0049] Figure 3 It is a cross-sectional view of a flexible microelectrode array structure according to an embodiment of the present application.

[0050] Figure 4 Schematic diagram of the process flow of a method for preparing a flexible microelectrode array according to an embodiment of the present application.

[0051] Description of Figure Numbers:

[0052] 100 flexible microelectrode array; 1 flexible substrate; 11 protrusion; 12 insulating layer; 2 brain signal metal electrode; 3 first metal conducting component; 31 first connection site; 32 connecting wire; 4 second metal conducting component; 41 second connection site. DETAILED DESCRIPTION

[0053] In order to make the purpose, technical solution and advantages of the present application clearer, the technical solution of the present application will be clearly and completely described below in combination with the embodiments of the present application. Obviously, the described embodiments are part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present application.

[0054] Flexible microelectrode arrays have good flexibility and stretchability, and can better fit with the interface of nerve cells, thereby achieving long-term stable culture of neuronal cells and real-time signal detection, and can also improve the sensitivity and quality of neuroelectrophysiological signal detection. Flexible microelectrode arrays can be used in the field of neuroscience to study brain function and nervous system diseases. By recording the electrical activity of different brain regions, the functional state and pathological changes of the brain can be understood. It can also be used in the study of brain-computer interfaces to help achieve direct communication between the human brain and computers or other devices.

[0055] Currently, the flexible electrode structure used in the cerebral cortex is generally a flat thin-film brain signal metal electrode with a certain height. In the long-term brain implantation environment, there are problems such as large implantation wounds, great damage to the human body, and inability to achieve integrated implantation.

[0056] For example, a brain-computer interface with gel microneedle brain electrodes is disclosed, which includes a plurality of microneedle electrodes, each of which includes a plurality of microneedles, and the microneedles include a gel electrolyte and a columnar electrode, the microneedle electrode has a hollow conical outer layer of biomimetic material, the columnar electrode passes through the inside of the gel electrolyte and is exposed from the tip of the microneedle, and the other side of the columnar electrode is connected to a metal film wire and fully covered with an insulating layer. The electrode is connected to a communication device through a flexible wire, and the brain-computer interface with gel microneedle brain electrodes disclosed in the present invention has low impedance and can quickly and accurately collect brain electrical signals. However, the gel microneedle brain electrode has a large area, and the implantation wound is large, which causes great damage to the human body, and cannot be implanted in an integrated manner.

[0057] A microneedle array brain-computer interface device and a preparation method thereof, discloses using a non-conductive material as an inter-needle insulating layer, preparing a plurality of through holes in the inter-needle insulating layer; preparing a plurality of metal pads on a conductive material layer; arranging a conductive material layer below the inter-needle insulating layer, and connecting the upper surface of the conductive material layer to the lower surface of the inter-needle insulating layer; processing the conductive material layer into a micro-columnar structure distributed in an array, so that the micro-columnar structures are mutually insulated; processing the micro-columnar structure into a micro-needle structure with a needle tip at the bottom end, forming a micro-needle array layer distributed in an array and with the needle tip facing downward; preparing an external lead for connecting an external circuit above the micro-needle array layer; preparing an electrode point on the needle tip of the micro-needle array layer; and obtaining a micro-needle array brain-computer interface device. The present invention has the advantages of reducing the process steps of the micro-needle array brain-computer interface device, improving production efficiency and yield, and reducing the processing cost of the device. However, silicon-based microneedles are prone to brittle fracture during implantation of Si-based array electrodes. In addition, this hard substrate material can easily cause cuts in brain tissue and is not convenient for integrated implantation when connected to subsequent devices via flexible wires.

[0058] In view of this, the present application provides a flexible microelectrode array for brain-computer interface and its preparation method, and a brain-computer interface device to solve the problems of multiple packaging times, large implantation wounds, and great damage to the human body.

[0059] First, as Figures 1 to 3As shown, the present application provides a flexible microelectrode array 100 for a brain-computer interface, comprising a flexible substrate 1, a plurality of brain signal metal electrodes 2, a first metal conduction component 3 and a second metal conduction component 4, wherein the flexible substrate 1 has a first side and a second side arranged opposite to each other; the plurality of brain signal metal electrodes 2 are arranged on the first side, and are spaced to form an electrode array; the first metal conduction component 3 is arranged on the second side of the flexible substrate 1 and is encapsulated in the flexible substrate 1, comprising a plurality of first connection sites 31 and a plurality of connecting wires 32; the second metal conduction component 4 comprises a plurality of second connection sites 41 exposed to the flexible substrate 1, and the second connection sites 41 are arranged on the first side or the second side of the flexible substrate 1; the plurality of first connection sites 31 are respectively connected to the plurality of brain signal metal electrodes 2, and are respectively connected to the plurality of second connection sites 41 through the plurality of connecting wires 32; the plurality of second connection sites 41 are used to communicate with the processor.

[0060] In the present application, when the flexible microelectrode array 100 is implanted in the brain, the brain signal metal electrode 2 contacts the nerves of the brain, and the first metal conduction component 3 is connected to the brain signal metal electrode 2 to transmit the brain signal received by the brain signal metal electrode 2 to the second metal conduction component 4. The second metal conduction component 4 transmits the signal to the processor through the second connection site 41 to achieve control or response. Since the multiple first connection sites 31 are respectively connected to the multiple brain signal metal electrodes 2, and are respectively connected to the multiple second connection sites 41 through the multiple connecting wires 32, the multiple first connection sites 31 and the multiple connecting wires 32 are encapsulated in the flexible substrate 1. Therefore, there is no need to additionally set leads connecting the first connection sites 31 and the second connection sites 41. The signals of the first connection sites 31 and the second connection sites 41 are directly connected through the patterned connecting wires 32. Since the second connection sites 41 are exposed, they can be directly welded to the solder joint array of the processor. After welding, it is only necessary to integrate the processor and the electrode array to achieve the packaging and protection of the entire flexible microelectrode array 100, without the need to encapsulate the leads connecting the first connection sites 31 and the second connection sites 41 again, and there is no need to lead out the leads, thereby reducing the volume of the flexible microelectrode array 100, making the implantation wound smaller, and causing less damage to the brain tissue.

[0061] It should be noted that there are two forms in which the second connection sites 41 are arranged on the first side or the second side of the flexible substrate 1 . One is that all the second connection sites 41 are arranged on the second side of the flexible substrate 1 ; the other is that all the second connection sites 41 are arranged on the first side of the flexible substrate 1 .

[0062] The first metal conducting component 3 is encapsulated in the insulating layer 12 on the second side of the flexible substrate 1, which can fix and protect the electrode, reduce the movement of the electrode, and reduce the damage to the brain tissue. The second metal conducting component 4 is exposed outside the insulating layer 12 on the first side or the second side of the flexible substrate 1, and can be directly welded to the solder joint array of the processor without additionally leading out the lead from the electrode array and performing secondary encapsulation on the lead. Without complex wire settings, large-area wire laying, and large implantation wounds, good signal conduction can be achieved.

[0063] The present application does not limit the shape of the flexible microelectrode array 100, which can be circular, square, triangular, rhombus or polygonal. It should be noted that in some embodiments, the brain signal metal electrode 2 can adopt a raised tip electrode structure design, which improves the mechanical strength of the electrode, improves the mechanical properties and ductility of long-term implantation, and meets the needs of long-term implantation. The flexible tip electrode array is easier to adapt to the curved surface of the cerebral cortex, reduces displacement and sliding under long-term implantation conditions, and makes signal transmission more accurate. In order to improve the biocompatibility of the flexible microelectrode array 100, a plurality of protrusions 11 containing mounting channels can be provided on the first side of the flexible substrate 1, and the brain signal metal electrodes 2 are respectively placed in the mounting channels of the protrusions 11, with the tip exposed, thereby increasing the pressure on the tip during implantation, reducing implantation resistance, and at the same time improving the accuracy of signal transmission and reducing the damage of hard metal materials to brain tissue.

[0064] In combination with the first aspect, in some embodiments provided in the present application, the second metal conductive component 4 is arranged on the peripheral side of the first metal conductive component 3. Since the first metal conductive component 3 is encapsulated in the insulating layer 12 on the second side of the flexible substrate 1 and is respectively connected to the plurality of brain signal metal electrodes 2, and the second metal conductive component 4 is exposed outside the insulating layer 12 on the second side of the flexible substrate 1 for connection with the processor, in order to reduce the interference of the second metal conductive component 4 on the first metal conductive component 3, the second metal conductive component 4 is arranged on the peripheral side of the first metal conductive component 3, so that the first metal conductive component 3 is located in the middle position and the second metal conductive component 4 is located at the edge position, and the wiring distance of the second metal conductive component 4 can also be reduced, which is convenient for connection with the processor.

[0065] In combination with the first aspect, in some embodiments provided in the present application, the material of the flexible substrate 1 includes at least one of polydimethylsiloxane, polymethyl methacrylate, polyimide, paraxylene polymer and silicone, which is a material with good biocompatibility, reducing the risk of rejection reaction.

[0066] In combination with the first aspect, in some embodiments provided in the present application, the material of the brain signal metal electrode 2 includes at least one of gold, silver, copper and platinum. The brain signal metal electrode 2 has good mechanical strength and ductility, meeting the needs of long-term implantation. Using at least one of the above materials can improve the stability of the brain signal metal electrode 2 and reduce the harm of electrode corrosion to the human body.

[0067] In combination with the first aspect, in some embodiments provided in the present application, the number of the brain signal metal electrodes 2 is 8 to 64. The electrode array formed by 8 to 64 brain signal metal electrodes 2 is usually a low-flux electrode array with a small amount of signal and low transmission resistance. The integrated packaging form can realize direct data transmission and reduce the transmission pressure caused by excessive data volume.

[0068] The shapes of the first connection sites 31 and the second connection sites 41 include, but are not limited to, square, circle, triangle, rhombus, trapezoid or polygon. The second connection sites 41 may be distributed at equal intervals or at non-equal intervals, and may be arranged only on one side of the flexible microelectrode array 100, on two opposite or adjacent sides, or on all sides.

[0069] It should be noted that the position and number of the first connection sites 31 correspond one-to-one to the brain signal metal electrodes 2, and the number of the second connection sites 41 corresponds to the number of the first connection sites 31, that is, each brain signal metal electrode 2 is connected to a first connection site 31, and each first connection site 31 is connected to a second connection site 41 through a connecting wire 32, thereby realizing the transmission of the signal of each brain signal metal electrode 2 to the processor, and the signals of each electrode do not interfere with each other and are transmitted independently.

[0070] It should be noted that the thickness of the flexible substrate 1 can be 10 to 70 μm. The total height of the brain signal metal electrode 2 can be 0.5 to 2 mm, the exposed height can be 0.1 to 0.5 mm, and the diameter can be 0.1 to 1.5 mm. The shape of the protrusion 11 can be cylindrical or conical. In order to improve the implantation efficiency and reduce the implantation resistance, the shape of the protrusion 11 is usually conical.

[0071] In a second aspect, the present application provides a method for preparing a flexible microelectrode array, comprising the following steps:

[0072] A flexible substrate having a plurality of protrusions arranged at intervals on one side is prepared;

[0073] A metal conductive layer including a plurality of connection sites and connection wires is prepared on a side of the flexible substrate without protrusions;

[0074] A flexible substrate material is used to encapsulate the connection sites and connection wires of a part of the metal conductive layer to form a plurality of first connection sites and a plurality of connection wires of a first metal conductive component, and another part of the connection sites of the metal conductive layer is exposed to form a plurality of second connection sites of a second metal conductive component;

[0075] A brain signal metal electrode installation channel is formed on the protrusion of the flexible substrate, and a brain signal metal electrode is prepared in the installation channel and connected to the first metal conducting component to obtain a flexible microelectrode array.

[0076] By preparing a metal conductive layer containing multiple connection sites and connecting wires on the side of the flexible substrate without protrusions, and using insulating materials to encapsulate and wrap part of the connection sites of the metal conductive layer to form a first metal conductive component, and exposing another part of the connection sites of the metal conductive layer to form a second metal conductive component, the reliability of the communication connection between the first metal conductive component and the second metal conductive component can be achieved, and the molding of the two metal conductive components can be achieved in one molding. By forming a brain signal metal electrode installation channel on the protrusion of the flexible substrate, preparing a brain signal metal electrode in the installation channel, and connecting it to the first metal conductive component, a flexible microelectrode array can be obtained. The number and size of electrodes can be customized according to the requirements of specific application scenarios, and the electrode shape suitable for different brain regions can be designed, which is more flexible and changeable. By patterning during the preparation of the metal conducting layer, a plurality of first connection sites and a plurality of connection wires of the first metal conducting component and a plurality of second connection sites of the second metal conducting component can be formed at one time. By encapsulating the plurality of first connection sites and the plurality of connection wires through a flexible substrate material, a reliable connection between the first connection site and the second connection site can be achieved. There is no need to lead out additional leads from the first connection site, and there is no need to encapsulate the leads additionally. The structure is simple, and data transmission is direct and real.

[0077] The insulating layer material includes, but is not limited to, PDMS (polydimethylsiloxane), PMMA (polymethyl methacrylate), PI (polyimide), Parylene-C (paraxylene polymer) and silicone, which are flexible materials with good biocompatibility. The material of this layer is selected to be consistent with the material of the flexible substrate layer to further improve flexibility and compatibility. The method of forming the insulating layer includes, but is not limited to, thin film deposition process (CVD, PVD), spin coating process, template casting process, electrochemical deposition process, etc.

[0078] In conjunction with the second aspect, in some embodiments provided in the present application, preparing a flexible substrate having a plurality of protrusions disposed at intervals on one side includes:

[0079] preparing a flexible mold layer on a substrate;

[0080] cutting a plurality of tapered holes arranged at intervals in the flexible mold layer;

[0081] A flexible substrate having a plurality of protrusions arranged at intervals is prepared on the side of the flexible mold layer having the tapered holes.

[0082] By cutting a plurality of tapered holes at intervals on the flexible mold layer, a flexible substrate containing a plurality of protrusions at intervals is prepared on the side of the flexible mold layer containing the tapered holes. The flexible substrate containing a plurality of protrusions at intervals can be prepared by means of a mold. The shape of the flexible substrate can be changed by changing the shape of the mold, which is more flexible and simple. The flexible mold layer and the substrate can be removed by demolding later. The substrate can be a hard substrate including but not limited to a silicon wafer and a quartz wafer, which improves the supporting force of the flexible substrate during preparation and reduces deformation. The flexible substrate containing a plurality of protrusions at intervals can be prepared by using a thin film deposition process (CVD, PVD), a template casting process, or an electrochemical deposition process to form the flexible substrate.

[0083] In combination with the second aspect, in some embodiments provided in the present application, the step of preparing a metal conductive layer including a plurality of connection sites and connection wires on a side of the flexible substrate without protrusions comprises:

[0084] Spin coating photoresist on a flexible substrate and obtaining a photoresist mask;

[0085] A metal layer is prepared under the cover of a photoresist mask, and the photoresist is removed to obtain a metal conductive layer containing multiple connection sites and connection wires.

[0086] Since the metal conductive layer is not a flat plane, but forms different conductive layer patterns according to the positions of the brain signal metal electrodes and the wires connecting the multiple brain signal metal electrodes, in order to prepare a metal conductive layer with a specific pattern, the photoresist mask is used to cover it. After the metal layer is prepared, the photoresist is removed to obtain a metal conductive layer containing multiple connection sites and connecting wires. The photoresist can be a positive photoresist or a negative photoresist. The positive photoresist is cured by light, and the negative photoresist is dissolved by light. The method for preparing the metal layer includes but is not limited to thin film deposition processes (CVD, PVD, evaporation), template casting processes, electrochemical deposition processes, electroplating processes, machining and other processes.

[0087] In combination with the second aspect, in some embodiments provided in the present application, a brain signal metal electrode mounting channel is formed on the protrusion of the flexible substrate, and a brain signal metal electrode is prepared in the mounting channel and connected to the first metal conductive component to obtain a flexible microelectrode array: the method of forming the brain signal metal electrode mounting channel includes laser cutting or dry etching. By forming the brain signal metal electrode mounting channel by laser cutting or dry etching on the flexible mold layer, the number, shape and position of the brain signal metal electrodes can be better controlled.

[0088] In combination with the second aspect, in some embodiments provided in the present application, a brain signal metal electrode installation channel is formed on the protrusion of the flexible substrate, and a brain signal metal electrode is prepared in the installation channel and connected to the first metal conductive component to obtain a flexible microelectrode array: the method for preparing the brain signal metal electrode includes any one of electrochemical deposition, capillary effect and metal welding. The brain signal metal electrode is prepared by electrochemical deposition, capillary effect and metal welding, and the preparation amount of the metal electrode can be controlled to achieve the expected effect.

[0089] In combination with the second aspect, in some embodiments provided in the present application, the material of the flexible substrate includes at least one of polydimethylsiloxane, polymethyl methacrylate, polyimide, paraxylene polymer and silicone, which is a material with good biocompatibility, reducing the risk of rejection reaction.

[0090] In combination with the second aspect, in some embodiments provided in the present application, the material of the brain signal metal electrode includes at least one of gold, silver, copper and platinum. The brain signal metal electrode has good mechanical strength and ductility, meeting the needs of long-term implantation. The use of at least one of the above materials can improve the stability of the brain signal metal electrode and reduce the harm of electrode corrosion to the human body.

[0091] In some embodiments of the present application, Figure 4 As shown, the steps of preparing the flexible microelectrode array may specifically be:

[0092] S10, spin coating a flexible material on the substrate to obtain a flexible mold;

[0093] S20, preparing a tapered hole structure on the flexible mold by laser etching but not limited to this process technology;

[0094] S30, spin coating a flexible material on the flexible mold to obtain a flexible substrate layer;

[0095] S40, depositing a wire metal layer on the flexible substrate layer by a PVD process;

[0096] S50, spin coating a photoresist on the surface of the metal layer, where the photoresist type can be a positive photoresist or a negative photoresist;

[0097] S60, exposing the photoresist layer using a photolithography machine, and developing the surface of the photoresist layer to reveal the wire metal layer area that needs to be etched;

[0098] S70, etching the exposed metal layer area through an etching process to form a metal conductor pattern;

[0099] S80, removing all photoresist on the surface (dry etching or wet etching);

[0100] S90, spin coating an insulating layer material on the metal wire pattern so that the insulating layer material wraps the metal wire;

[0101] S100, spin coating a photoresist on the surface of the insulating layer material, and the photoresist type can be positive photoresist or negative photoresist;

[0102] S110, exposing the photoresist by a photolithography machine, and developing the surface of the photoresist to reveal the insulating layer area to be etched;

[0103] S120, etching the area of ​​the insulating layer to be etched by dry etching to form a metal wire window;

[0104] S130, removing all photoresist on the surface;

[0105] S140, spin coating and stripping photoresist on the surface of the insulating layer material, the photoresist type can be positive photoresist or negative photoresist;

[0106] S150, exposing the photoresist by a photolithography machine, and developing the surface of the photoresist to reveal the metal wire window to be etched;

[0107] S160, depositing metal contacts in the metal wire window by a PVD process to form a plurality of second connection sites;

[0108] S170, removing the surface stripping photoresist through a stripping process;

[0109] S180, separating the flexible mold layer from the flexible substrate layer to obtain a flexible substrate with a protruding tip structure;

[0110] S190, turning over the flexible substrate;

[0111] S200, spin coating a photoresist on one side of the tip structure of the flexible substrate, and the photoresist type can be positive photoresist or negative photoresist;

[0112] S210, exposing the photoresist by a photolithography machine, and developing the surface of the photoresist to reveal the metal tip window to be etched;

[0113] S220, etching the protruding tip structure to prepare a through-hole structure, wherein the etching method includes but is not limited to laser etching and dry etching;

[0114] S230, removing all photoresists;

[0115] S240, preparing a conductive metal material in the through-hole structure to obtain a metal tip structure, i.e., a metal electrode, wherein the preparation means include but are not limited to electrochemical deposition, metal welding, siphoning and other methods.

[0116] in Figure 4 (a) is a process flow chart of step S10 to step S40, Figure 4(b) is a process flow chart of step S50 to step S80, Figure 4 (c) is a process flow chart of step S90 to step S120, Figure 4 (d) is a process flow chart of step S130 to step S160, Figure 4 (e) is a process flow chart of step S170 to step S200, Figure 4 (f) is a process flow chart of step S210 to step S240.

[0117] In a third aspect, the present application proposes a brain-computer interface device, comprising the flexible microelectrode array of the first aspect of the present application.

[0118] In summary, when the flexible microelectrode array is implanted in the brain, the brain signal metal electrode contacts the nerves of the brain, and the first metal conductive component transmits the brain signal received by the brain signal metal electrode to the second metal conductive component by connecting to the brain signal metal electrode, and the second metal conductive component transmits the signal to the processor through the connection site to achieve control or response. Since the plurality of the first connection sites are respectively connected to the plurality of the brain signal metal electrodes, and are respectively connected to the plurality of second connection sites through a plurality of connecting wires, the plurality of first connection sites and the plurality of connecting wires are encapsulated in the flexible substrate, and therefore, there is no need to additionally set up leads connecting the first connection sites to the second connection sites, and the signals of the first connection sites to the second connection sites are directly connected through patterned connecting wires, and since the second connection sites are exposed, they can be directly welded to the solder joint array of the processor, and after welding, only the processor and the electrode array need to be integrated to achieve the packaging and protection of the entire flexible microelectrode array, without the need to encapsulate the leads connecting the first connection sites to the second connection sites once more, and there is no need to lead out the leads, which reduces the volume of the flexible microelectrode array, makes the implantation wound smaller, and causes less damage to the brain tissue.

[0119] In the description of the present application, it should be noted that the terms "upper", "lower", etc. indicate orientations or positional relationships based on the orientations or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present application and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation on the present application. Unless otherwise clearly specified and limited, the terms "installed", "connected", and "connected" should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection, or it can be an indirect connection through an intermediate medium, or it can be a connection between the two elements. For those of ordinary skill in the art, the specific meanings of the above terms in the present application can be understood according to the specific circumstances.

[0120] It should be noted that, in this application, relational terms such as "first" and "second" are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms "include", "comprise" or any other variants thereof are intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or device. In the absence of further restrictions, the elements defined by the sentence "comprise a ..." do not exclude the presence of other identical elements in the process, method, article or device including the elements.

[0121] The above description is only a specific implementation of the present application, so that those skilled in the art can understand or implement the present application. Various modifications to these embodiments will be apparent to those skilled in the art, and the general principles defined herein can be implemented in other embodiments without departing from the spirit or scope of the present application. Therefore, the present application will not be limited to the embodiments shown herein, but will conform to the widest scope consistent with the principles and novel features applied for herein.

Claims

1. A flexible microelectrode array for brain-computer interface, characterized in that: include: A flexible substrate having a first side and a second side disposed opposite to each other; A plurality of metal electrodes for brain signals are disposed on the first side and spaced apart to form an electrode array; A first metal conductive component is disposed on the second side of the flexible substrate and is encapsulated in the flexible substrate, comprising a plurality of first connection sites and a plurality of connection wires; as well as, A second metal conductive component includes a plurality of second connection sites exposed to the flexible substrate, wherein the second connection sites are arranged on the first side or the second side of the flexible substrate; Wherein, a plurality of the first connection sites are respectively connected to a plurality of the brain signal metal electrodes, and are respectively connected to a plurality of the second connection sites through a plurality of connecting wires; The plurality of second connection sites are used for communication connection with the processor.

2. The flexible microelectrode array for brain-computer interface according to claim 1, characterized in that: The second metal conducting component is arranged on the peripheral side of the first metal conducting component.

3. The flexible microelectrode array for brain-computer interface according to claim 1, characterized in that: The material of the flexible substrate includes at least one of polydimethylsiloxane, polymethyl methacrylate, polyimide, p-xylene polymer and silica gel; and / or, The material of the brain signal metal electrode includes at least one of gold, silver, copper and platinum.

4. The flexible microelectrode array for brain-computer interface according to claim 1, characterized in that: The number of the brain signal metal electrodes is 8 to 64.

5. A method for preparing a flexible microelectrode array for a brain-computer interface, characterized in that: The following steps are involved: A flexible substrate having a plurality of protrusions arranged at intervals on one side is prepared; A metal conductive layer including a plurality of connection sites and connection wires is prepared on a side of the flexible substrate without protrusions; A flexible substrate material is used to encapsulate the connection sites and connection wires of a part of the metal conductive layer to form a plurality of first connection sites and a plurality of connection wires of a first metal conductive component, and another part of the connection sites of the metal conductive layer is exposed to form a plurality of second connection sites of a second metal conductive component; A brain signal metal electrode installation channel is formed on the protrusion of the flexible substrate, a brain signal metal electrode is prepared in the installation channel, and the metal electrode is connected to the first metal conducting component to obtain a flexible microelectrode array; The plurality of first connection sites are respectively connected to the plurality of second connection sites through a plurality of connection wires.

6. The method for preparing a flexible microelectrode array for a brain-computer interface according to claim 5, characterized in that: The method of preparing a flexible substrate having a plurality of protrusions arranged at intervals on one side comprises: preparing a flexible mold layer on a substrate; cutting a plurality of tapered holes arranged at intervals in the flexible mold layer; A flexible substrate having a plurality of protrusions arranged at intervals is prepared on the side of the flexible mold layer having the tapered holes.

7. The method for preparing a flexible microelectrode array for a brain-computer interface according to claim 5, characterized in that: The step of preparing a metal conductive layer including a plurality of connection sites and connection wires on a side of the flexible substrate without protrusions comprises: Spin coating photoresist on a flexible substrate and obtaining a photoresist mask; A metal layer is prepared under the cover of a photoresist mask, and the photoresist is removed to obtain a metal conductive layer containing multiple connection sites and connection wires.

8. The method for preparing a flexible microelectrode array for a brain-computer interface according to claim 5, characterized in that: The brain signal metal electrode installation channel is formed on the protrusion of the flexible substrate, and the brain signal metal electrode is prepared in the installation channel and connected to the first metal conducting component to obtain the flexible microelectrode array: The method of forming the brain signal metal electrode installation channel includes laser cutting or dry etching; and / or, The method for preparing the metal electrode for brain signals includes any one of electrochemical deposition, capillary effect and metal welding.

9. The method for preparing a flexible microelectrode array for a brain-computer interface according to claim 5, characterized in that: The material of the flexible substrate includes at least one of polydimethylsiloxane, polymethyl methacrylate, polyimide, p-xylene polymer and silica gel; and / or, The material of the brain signal metal electrode includes at least one of gold, silver, copper and platinum.

10. A brain-computer interface device, characterized in that: Comprising a flexible microelectrode array for brain-computer interface as described in any one of claims 1 to 4.

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