Implantable soluble microneedle array electrode and preparation method thereof

Abstract

The invention discloses an implantable soluble microneedle array electrode and a preparation method thereof, and the microneedle array electrode comprises a substrate which is made of a degradable flexible material and comprises a microneedle substrate and a plurality of microneedles; the flexible electrode substrate is covered on the microneedle substrate and the microneedle; the flexible electrode conducting layer covers the surface of the flexible electrode substrate; the flexible electrode insulating layer is arranged on the surface of the flexible electrode conducting layer, the part, corresponding to the needle tip of the microneedle, of the flexible electrode conducting layer is exposed out of the flexible electrode insulating layer and forms an electrode point, and the length of the electrode point is smaller than 100 micrometers. Mechanical mismatching between the electrode and the cerebral cortex is reduced, long-term implantation is facilitated, potential signals can be collected in real time during implantation, an implantation functional area can be positioned conveniently, meanwhile, the electrode point at the tip can accurately collect corresponding neuron action potential or field potential, signal crosstalk is reduced, and the spatial resolution of signal collection is improved.

Description

Technical Field

[0001] The present invention relates to the technical field of brain function detection, and in particular to an implantable soluble microneedle array electrode and a preparation method thereof. Background Art

[0002] Brain-Computer Interface (BCI) refers to a direct connection between the human or animal brain and an external device to achieve information exchange between the brain and the device. BCI technology has achieved a series of achievements in brain science and clinical practice. With the help of BCI technology, paralyzed patients can control robotic arms with their minds, spell with their minds, and assist in the recovery of body functions.

[0003] As the front end of the brain-computer interface system, electrodes will significantly affect the signal quality, thereby affecting the performance of the entire brain-computer interface system; invasive electrodes implanted in the cerebral cortex can collect the action potential of single neurons and the field potential of neuronal clusters. A typical representative of these is the Utah Electrode Array (UEA). The unique silicon-based three-dimensional microneedle array structure of the Utah electrode has high spatial resolution.

[0004] However, invasive brain-computer interface electrodes represented by the Utah electrode have the following limitations: (1) The needle body and substrate of the Utah or Utah-like electrode are made of hard materials such as silicon and metal. Long-term implantation will cause a large mechanical mismatch with the cerebral cortex, thereby causing side effects after implantation and causing electrode failure, which cannot meet the needs of long-term implantation. (2) Flexible electrodes usually use polymer materials with a lower Young's modulus, which is closer to the Young's modulus of the brain and has higher biocompatibility, making them suitable for long-term implantation. However, the flexible electrode implantation process requires the use of a rigid guide needle or wrapping it in a soluble material. The flexible electrode probe will be pulled out during the removal of the guide needle, affecting the implantation accuracy. Flexible electrodes wrapped in soluble materials are difficult to achieve high-precision positioning and arraying. In addition, during the implantation process, the soluble material will affect the acquisition of electrical signals, making it impossible to judge the implanted functional area through the signal, affecting the implantation accuracy. Summary of the invention

[0005] The main purpose of the present invention is to provide an implantable soluble microneedle array electrode and a preparation method thereof, so as to solve the problem of limitations of implantable electrodes in the implantation process and long-term application in the related art.

[0006] In order to achieve the above object, the present invention provides an implantable soluble microneedle array electrode, comprising:

[0007] A substrate, wherein the substrate is made of a degradable flexible material and comprises a microneedle substrate and a plurality of microneedles;

[0008] A flexible electrode substrate, the flexible electrode substrate covers the microneedle substrate and the microneedles, and the flexible electrode substrate is made of insulating material;

[0009] A flexible electrode conductive layer, wherein the flexible electrode conductive layer covers the surface of the flexible electrode substrate;

[0010] A flexible electrode insulating layer is arranged on the surface of the flexible electrode conductive layer, and a portion of the flexible electrode conductive layer corresponding to the needle tip of the microneedle is exposed outside the flexible electrode insulating layer to form an electrode point, and the length of the electrode point is less than 100 μm.

[0011] Furthermore, the microneedle substrate is made of a different material from the microneedles, and the dissolution rate of the microneedle substrate is greater than the dissolution rate of the microneedles.

[0012] Furthermore, the bottom diameter of the microneedle is 50 μm-300 μm, and the center distance between adjacent microneedles is 100 μm-1 mm.

[0013] Furthermore, the thickness of the flexible electrode substrate is 500nm-100μm, the thickness of the flexible electrode conductive layer is 10nm-10μm, and the bottom diameter of the electrode point is 5-100μm.

[0014] According to another aspect of the present invention, a method for preparing an implantable soluble microneedle array electrode is provided, the method comprising:

[0015] Providing an elastic mold, wherein the elastic mold comprises a plurality of micro pinholes;

[0016] Casting a degradable flexible material on the surface of the microneedle hole and the elastic mold and curing the material to form a substrate having a microneedle substrate and a plurality of microneedles;

[0017] Peeling the substrate off the elastic mold, and fixing the peeled substrate onto a flat substrate;

[0018] Growing a flexible electrode substrate on the surface of the microneedle substrate and the microneedles using an insulating material;

[0019] Growing a metal layer on the surface of the flexible electrode substrate, and patterning the metal layer to form a flexible electrode conductive layer;

[0020] Growing a flexible electrode insulating layer on the surface of the flexible electrode conductive layer using an insulating material;

[0021] A window is opened on a portion of the flexible electrode insulating layer corresponding to the needle tip of the microneedle to expose the tip of the flexible electrode conductive layer to form an electrode point, wherein the length of the electrode point is less than 100 μm.

[0022] Furthermore, the elastic mold is prepared by the following method:

[0023] Providing a rigid mold, the rigid mold comprising a rigid substrate and a rigid microneedle array disposed on the rigid substrate;

[0024] Placing the rigid mold in a container, pouring elastic material into the rigid mold and heating and curing it to form the elastic mold;

[0025] The elastic mold is peeled off from the rigid mold.

[0026] Furthermore, before pouring the degradable flexible material, the required drugs are mixed into the degradable flexible material.

[0027] Furthermore, a degradable flexible material is poured on the surface of the microneedle hole and the elastic mold and solidified to form a substrate having a microneedle substrate and a plurality of microneedles, comprising:

[0028] pouring a first degradable flexible material into the microneedle holes and curing the material to form a plurality of microneedles;

[0029] Covering the elastic mold with a second degradable flexible material and curing it to form a microneedle substrate, wherein the microneedle substrate and the microneedle are bonded to form the base;

[0030] The dissolution rate of the second degradable flexible material is greater than the dissolution rate of the first degradable flexible material.

[0031] Furthermore, the second degradable material carries the desired drug.

[0032] Furthermore, the thickness of the flexible electrode substrate is 500nm-100μm, the thickness of the flexible electrode conductive layer is 10nm-10μm, and the bottom diameter of the electrode point is 5-100μm.

[0033] In the embodiment of the present invention, a substrate is provided, the substrate is made of a degradable flexible material, and the substrate includes a microneedle substrate and a plurality of microneedles; a flexible electrode substrate, the flexible electrode substrate covers the microneedle substrate and the microneedles, and the flexible electrode substrate is made of an insulating material; a flexible electrode conductive layer, the flexible electrode conductive layer covers the surface of the flexible electrode substrate; a flexible electrode insulating layer, the flexible electrode insulating layer is provided on the surface of the flexible electrode conductive layer, the portion of the flexible electrode conductive layer corresponding to the needle tip of the microneedle is exposed outside the flexible electrode insulating layer and forms an electrode point, and the length of the electrode point is less than 100 μm. On the one hand, a degradable flexible material is used as the substrate material, which has high mechanical strength before and during electrode implantation, and facilitates electrode implantation. After implantation, as the soluble material gradually dissolves or degrades, the Young's modulus of the needle tip and the substrate will be significantly reduced, thereby reducing the mechanical mismatch between the electrode and the cerebral cortex, and is suitable for long-term implantation;

[0034] On the other hand, the flexible electrode conductive layer is wrapped on the outer surface of the soluble substrate. During the implantation process, the signal collection of the flexible electrode conductive layer is not affected by the dissolution process of the substrate. Therefore, the potential signal can be collected in real time during implantation, which is convenient for locating the implanted functional area. In addition, since the soluble substrate does not need to be dissolved quickly to quickly obtain the potential signal during the implantation process, the requirement for the dissolution rate of the substrate is reduced. When the substrate carries the drug, the release process of the drug can be better controlled by controlling the dissolution rate of the substrate.

[0035] On the other hand, since the portion of the flexible electrode conductive layer corresponding to the needle tip of the microneedle is exposed outside the flexible electrode insulating layer and forms an electrode point with a shorter length, during the electrode implantation process, the electrode point can accurately contact a single neuron, thereby accurately collecting the corresponding neuron action potential or field potential, reducing signal crosstalk, and improving the spatial resolution and accuracy of signal collection;

[0036] On the other hand, a flexible electrode insulating layer is provided between the soluble substrate and the flexible electrode conductive layer. Even if the substrate dissolves after implantation, the flexible electrode insulating layer can still ensure that the microneedles remain insulated, thereby reducing signal crosstalk between the microneedles. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] The accompanying drawings constituting a part of the present invention are used to provide a further understanding of the present invention, so that other features, purposes and advantages of the present invention become more obvious. The accompanying drawings of the exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute an improper limitation of the present invention. In the accompanying drawings:

[0038] Figure 1 is a schematic structural diagram of a microneedle array electrode according to an embodiment of the present invention;

[0039] Figure 2 is a schematic structural diagram of a rigid mold according to an embodiment of the present invention;

[0040] Figure 3 is a schematic diagram of preparing an elastic mold according to an embodiment of the present invention;

[0041] Figure 4 is a schematic structural diagram of an elastic mold according to an embodiment of the present invention;

[0042] Figure 5 is a schematic diagram of preparing a substrate according to an embodiment of the present invention;

[0043] Figure 6 is a schematic structural diagram of a substrate according to an embodiment of the present invention;

[0044] Figure 7 is a schematic diagram of preparing a flexible electrode substrate according to an embodiment of the present invention;

[0045] Figure 8 is a schematic diagram of preparing a flexible electrode conductive layer according to an embodiment of the present invention;

[0046] Fig. 9 is a schematic diagram of preparing a flexible electrode insulating layer and electrode points according to an embodiment of the present invention;

[0047] Fig.10 is a schematic diagram of preparing a microneedle according to another embodiment of the present invention;

[0048] Fig.11 is a schematic diagram of preparing a microneedle substrate according to another embodiment of the present invention;

[0049] Among them, 1 substrate, 10 microneedle substrate, 11 microneedle, 2 flexible electrode substrate, 3 flexible electrode conductive layer, 4 flexible electrode insulating layer, 5 electrode point, 6 rigid substrate, 61 rigid microneedle array, 7 elastic mold, 70 microneedle hole. DETAILED DESCRIPTION

[0050] In order to enable those skilled in the art to better understand the scheme of the present invention, the technical scheme in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work should fall within the scope of protection of the present invention.

[0051] It should be noted that the terms "first", "second", etc. in the specification and claims of the present invention and the above-mentioned drawings are used to distinguish similar objects, and are not necessarily used to describe a specific order or sequence. It should be understood that the numbers used in this way can be interchanged under appropriate circumstances to facilitate the embodiments of the present invention described herein.

[0052] In the present invention, the directions or positional relationships indicated by the terms "upper", "lower", "inner", etc. are based on the directions or positional relationships shown in the drawings. These terms are mainly used to better describe the present invention and its embodiments, and are not used to limit the indicated devices, elements or components to have a specific direction, or to be constructed and operated in a specific direction.

[0053] In addition, some of the above terms may be used to express other meanings in addition to indicating orientation or positional relationship. For example, the term "on" may also be used to express a certain dependency or connection relationship in some cases. For those skilled in the art, the specific meanings of these terms in the present invention can be understood according to specific circumstances.

[0054] In addition, the terms "disposed", "provided with", "connected", "fixed" and the like should be understood in a broad sense. For example, "connected" can be a fixed connection, a detachable connection, or an integral structure; it can be a mechanical connection, or an electrical connection; it can be a direct connection, or an indirect connection through an intermediate medium, or it can be an internal connection between two devices, elements or components. For those of ordinary skill in the art, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0055] In addition, the term "plurality" shall mean two or more.

[0056] It should be noted that, in the absence of conflict, the embodiments of the present invention and the features in the embodiments can be combined with each other. The present invention will be described in detail below with reference to the accompanying drawings and in combination with the embodiments.

[0057] To solve relevant technical problems, such as Figure 1 As shown, an embodiment of the present invention provides an implantable soluble microneedle array electrode, comprising:

[0058] A substrate 1, which is made of a degradable flexible material and includes a microneedle substrate 10 and a plurality of microneedles 11;

[0059] A flexible electrode substrate 2, the flexible electrode substrate 2 covers the microneedle substrate 10 and the microneedle 11, and the flexible electrode substrate 2 is made of insulating material;

[0060] A flexible electrode conductive layer 3, wherein the flexible electrode conductive layer 3 covers the surface of the flexible electrode substrate 2;

[0061] The flexible electrode insulating layer 4 is arranged on the surface of the flexible electrode conductive layer 3. The portion of the flexible electrode conductive layer 3 corresponding to the needle tip of the microneedle 11 is exposed outside the flexible electrode insulating layer 4 to form an electrode point 5. The length of the electrode point 5 is less than 100 μm.

[0062] In this embodiment, the implantable soluble microneedle array electrode mainly includes a substrate 1, a flexible electrode substrate 2, a flexible electrode conductive layer 3 and a flexible electrode insulating layer 4, wherein the innermost layer is the substrate 1, and the outer layers are the flexible electrode substrate 2, the flexible electrode conductive layer 3 and the flexible electrode insulating layer 4 in sequence.

[0063] The substrate 1 includes a microneedle substrate 10 and a plurality of microneedles 11 formed on the microneedle substrate 10. The plurality of microneedles 11 form a microneedle array, and the center distance between adjacent microneedles 11 can be set according to demand. In this embodiment, the microneedle 11 is a sharp and slender structure, which can be set to a cone or a pyramid. In order to enable the microneedle array electrode to have sufficient mechanical strength during the implantation process to facilitate implantation, it can have sufficient flexibility after implantation to facilitate long-term maintenance in the implanted state. In this embodiment, the substrate 1 is made of a degradable flexible material, and the materials used for the microneedle substrate 10 and the microneedle 11 in the substrate 1 may be the same or different. During preparation, it can be formed by mold casting or etching, and this embodiment does not limit it here. The degradable flexible material can be a material that can be dissolved or degraded in the body, such as polyvinyl alcohol, polyvinyl pyrrolidone, hyaluronic acid, glucose, etc.

[0064] Before degradation, the Young's modulus of the microneedle array electrode is relatively high, so that the microneedle array electrode has a certain mechanical strength, so that the mechanical strength of the entire microneedle array electrode can meet the implantation requirements. After degradation, the microneedle array electrode only retains the flexible electrode substrate 2, the flexible electrode conductive layer 3 and the flexible electrode insulating layer 4 with better flexibility, so that the Young's modulus of the microneedle array electrode is significantly reduced, thereby reducing the mechanical mismatch between the electrode and the cerebral cortex, and is suitable for long-term implantation.

[0065] In this embodiment, a flexible electrode substrate 2 is provided between the flexible electrode conductive layer 3 and the substrate 1, and the flexible electrode substrate 2 is an insulating material. After implantation, the substrate 1 dissolves, and at this time, the flexible electrode substrate 2 contacts the cerebrospinal fluid. The flexible electrode conductive layer 3 is isolated from the cerebrospinal fluid by the flexible electrode substrate 2, so that the electrodes of each microneedle 11 in the microneedle array electrode can be kept insulated to avoid crosstalk between signals. In this embodiment, the flexible electrode substrate 2 covers the surface of the microneedle substrate 10 and the microneedle 11 in the substrate 1. During preparation, insulating materials such as polyparaxylene or polyimide can be wrapped on the surface of the microneedle substrate 10 and the microneedle 11 by chemical vapor deposition or spraying processes to form an insulating flexible electrode substrate 2.

[0066] As for the flexible electrode conductive layer 3, it is covered on the flexible electrode substrate 2. The flexible electrode conductive layer 3 is used as the part for collecting and transmitting the potential signal, and is made of a conductive material. In this embodiment, one microneedle 11 corresponds to a layer of flexible electrode conductive layer 3, and the flexible electrode conductive layers 3 corresponding to adjacent microneedles 11 are insulated to avoid signal crosstalk. In this embodiment, the surface of the flexible electrode conductive layer 3 is also covered with a flexible electrode insulating layer 4, and the flexible electrode insulating layer 4 is made of an insulating material. During preparation, insulating materials such as polyparaxylene or polyimide can be covered on the surface of the flexible electrode conductive layer 3 by processes such as chemical vapor deposition or spraying. Since the flexible electrode conductive layer 3 needs to collect the potential signal, a part of the flexible conductive layer needs to be exposed outside the flexible electrode insulating layer 4, and the exposed part is used to contact the position where the potential signal needs to be collected, and the unexposed part is kept insulated from the brain tissue under the action of the flexible electrode insulating layer 4.

[0067] It is understandable that the portion of the flexible electrode conductive layer 3 that exposes the flexible electrode insulating layer 4 can contact the brain tissue, so the exposed position and the length of the microneedle will determine the position and depth at which the flexible electrode conductive layer 3 can contact the brain tissue. Since the position of the neuron in the brain has a certain depth and the diameter of the neuron is small, if the action potential of the neuron is to be accurately collected, the exposed portion of the flexible electrode conductive layer 3 needs to match the position of the neuron. To this end, in this embodiment, the portion of the flexible electrode conductive layer 3 corresponding to the needle tip of the microneedle 11 is exposed outside the flexible electrode insulating layer 4 and forms an electrode point 5, and the length of the electrode point 5 is less than 100 μm. Specifically, in this embodiment, only the tip portion of the flexible electrode conductive layer 3 corresponding to the needle tip of the microneedle 11 is exposed to form an electrode point 5, and the electrode point 5 is located at the tip of the microneedle array electrode and has a small length. After implantation, only the electrode point 5 on the flexible electrode conductive layer 3 can contact the neuron, and the rest of the flexible electrode insulating layer 4 remains insulated from the brain tissue, thereby enabling high-resolution neuronal electrical signal acquisition and collecting the action potential of a single neuron.

[0068] In this embodiment, the length of the electrode point 5 can be designed within a range of less than 100 μm according to the actual implantation object, and can meet the requirements of accurately collecting neuronal electrical signals.

[0069] On the one hand, the present invention uses a degradable flexible material as the substrate 1 material, which has high mechanical strength before and during electrode implantation, making electrode implantation convenient. After implantation, as the soluble material gradually dissolves or degrades, the Young's modulus of the needle tip and the substrate will be significantly reduced, thereby reducing the mechanical mismatch between the electrode and the cerebral cortex, making it suitable for long-term implantation.

[0070] On the other hand, the flexible electrode conductive layer 3 is wrapped on the outer surface of the soluble substrate 1. During the implantation process, the signal collection of the flexible electrode conductive layer 3 is not affected by the dissolution process of the substrate 1. Therefore, the potential signal can be collected in real time during implantation, which is convenient for locating the implantation functional area. In addition, since the soluble substrate 1 does not need to be dissolved quickly to quickly obtain the potential signal during the implantation process, the requirement for the dissolution rate of the substrate 1 is reduced. When the substrate 1 carries the drug, the release process of the drug can be better controlled by controlling the dissolution rate of the substrate 1.

[0071] On the other hand, since the portion of the flexible electrode conductive layer 3 corresponding to the needle tip of the microneedle 11 is exposed outside the flexible electrode insulating layer 4 and forms an electrode point 5 with a shorter length, during the electrode implantation process, the electrode point 5 can accurately contact a single neuron, so that the corresponding neuron action potential or field potential can be accurately collected, reducing signal crosstalk and improving the accuracy of signal collection;

[0072] On the other hand, a flexible electrode insulating layer 4 is provided between the soluble substrate 1 and the flexible electrode conductive layer 3. Even if the substrate 1 is dissolved after implantation, the flexible electrode insulating layer 4 can still ensure that the microneedles 11 remain insulated, thereby reducing signal crosstalk between the microneedles 11.

[0073] For the substrate 1 in the microneedle array electrode, it includes a microneedle substrate 10 and a microneedle 11, and both the microneedle substrate 10 and the microneedle 11 are made of degradable flexible materials. Since the microneedle substrate 10 serves as the basic structure of the microneedle array electrode, the microneedle substrate 10 has a greater influence on the Young's modulus of the microneedle array electrode. Therefore, after the microneedle substrate 10 is provided, the microneedle array electrode can have sufficient mechanical strength before and during implantation, but at the same time, the bending ability of the microneedle array electrode will be reduced. After implantation, it is expected that the Young's modulus of the microneedle array electrode can be rapidly reduced, so that the microneedle 11 electrode array can be better bent, so that it can better fit in the cerebral cortex.

[0074] For this reason, the degradable flexible material used in the microneedle substrate 10 in this embodiment is different from the degradable flexible material used in the microneedle 11, and the dissolution rate of the microneedle substrate 10 is greater than the dissolution rate of the microneedle 11, so that the microneedle substrate 10 can be dissolved in a short time after the microneedle array electrode is implanted in the brain, and the bending ability of the microneedle array electrode is better after dissolution, thereby ensuring that the flexible electrode substrate 2 can better fit the cerebral cortex. Since the microneedle 11 is wrapped in the flexible electrode conductive layer 3 and the flexible electrode substrate 2, the drug carried in the microneedle 11 after implantation can be slowly dissolved during the long-term implantation process, so as to achieve slow release of the drug.

[0075] In addition, after the microneedle substrate 10 adopts a material with a higher dissolution rate, the microneedle substrate 10 can choose not to carry drugs, thereby saving drugs, and the microneedle substrate 10 can also choose a degradable material that does not carry drugs, thereby increasing the types of material choices.

[0076] The different dissolution rates between the microneedle substrate 10 and the microneedles 11 can be achieved by changing the molecular weight of the soluble material, the type of material, the solute concentration, etc., which will not be described in detail in this embodiment.

[0077] In one embodiment, the thickness of the microneedle substrate 10 is 1 μm-500 μm, the height of the microneedle 11 is 100 μm-5 mm, the bottom diameter of the microneedle 11 is 50 μm-300 μm, and the center distance between adjacent microneedles 11 is 100 μm-1 mm. In one embodiment, the thickness of the flexible electrode substrate 2 is 500 nm-100 μm, the thickness of the flexible electrode conductive layer 3 is 10 nm-10 μm, and the bottom diameter of the electrode point 5 is 5-100 μm.

[0078] According to another aspect of the present invention, a method for preparing an implantable soluble microneedle array electrode is provided, the method comprising:

[0079] like Figure 4 As shown, an elastic mold 7 is provided, and the elastic mold 7 includes a plurality of microneedle 11 holes. In a specific embodiment, the elastic mold 7 may be a silicone rubber mold, and the elastic mold 7 may be formed by etching or casting and peeling using a conformal micromolding method based on another mold. The elastic mold 7 may be square as a whole, and a plurality of microneedle 11 holes are formed in the elastic mold 7, and the size, position and spacing of the microneedle 11 holes match the microneedle 11 electrodes in the microneedle 11 electrode array.

[0080] like Figure 5 As shown, a degradable flexible material is poured on the surface of the microneedle 11 hole and the elastic mold 7 and cured to form a substrate 1 having a microneedle substrate 10 and a plurality of microneedles 11. In a specific embodiment, a degradable flexible material or a degradable flexible material carrying a drug is covered on the surface of the elastic mold 7, and the degradable flexible material is made to flow into the microneedle 11 hole. The degradable flexible material can be filled into the microneedle 11 hole by vacuuming or centrifugation, and the substrate 1 having a microneedle substrate 10 and a plurality of microneedles 11 is formed after heating and curing.

[0081] like Figure 6 As shown, the substrate 1 is peeled off from the elastic mold 7, and the peeled substrate 1 is fixed to a flat substrate;

[0082] like Figure 7As shown, an insulating material is grown on the surface of the microneedle substrate 10 and the microneedle 11 to form a flexible electrode substrate 2. In a specific embodiment, after the microneedle substrate 10 is fixed to a substrate with a flat surface, an insulating material such as polyparaxylene or polyimide can be wrapped on the surface of the microneedle substrate 10 and the surface of the microneedle 11 by chemical vapor deposition or spraying to form a flexible substrate.

[0083] like Figure 8 As shown, a metal layer is grown on the surface of the flexible electrode substrate 2, and the metal layer is patterned to form a flexible electrode conductive layer 3. In a specific embodiment, after the metal layer is grown, the metal layer can be patterned by a mask photolithography process and a physical vapor deposition process, thereby preparing a flexible electrode conductive layer 3, and making the surface of each microneedle 11 covered with a conductive circuit, and the wires on the surface of each microneedle 11 are insulated from each other.

[0084] like Fig. 9 As shown, an insulating material is grown on the surface of the flexible electrode conductive layer 3 to form a flexible electrode insulating layer 4. In a specific embodiment, an insulating material such as polyparaxylene or polyimide is wrapped on the surface of the flexible electrode conductive layer 3 by chemical vapor deposition or spraying process to form the flexible electrode insulating layer 4.

[0085] The portion of the flexible electrode insulating layer 4 corresponding to the needle tip of the microneedle 11 is opened to expose the tip of the flexible electrode conductive layer 3 to form an electrode point 5, and the length of the electrode point 5 is less than 100 μm. In a specific embodiment, after the flexible electrode insulating layer 4 is prepared and formed, the flexible electrode insulating layer 4 completely covers the flexible electrode conductive layer 3. In order to enable at least a portion of the flexible electrode conductive layer 3 to contact the brain tissue to collect electrical signals, the flexible electrode insulating layer 4 needs to be opened. In this embodiment, the electrode window is completed on the portion of the flexible electrode insulating layer 4 corresponding to the needle tip of the microneedle 11 to form an electrode point 5 through a maskless photolithography process and an etching process.

[0086] Of course, during the process of forming the flexible electrode insulating layer 4 , a mask may be used to protect the tip of the flexible electrode conductive layer 3 , and after the flexible electrode insulating layer 4 is formed, the mask may be removed to form the electrode point 5 .

[0087] like Figure 2 As shown, a rigid mold is provided, and the rigid mold includes a rigid substrate 6 and a rigid microneedle array disposed on the rigid substrate 6. In a specific embodiment, the rigid mold can be prepared by mechanical preparation or 3D printing and other molding technologies;

[0088] like Figure 3 As shown, a rigid mold is placed in a container, and an elastic material is poured into the rigid mold and heated and cured to form an elastic mold 7;

[0089] like Figure 4 As shown, the elastic mold 7 is peeled off from the rigid mold.

[0090] Furthermore, before pouring the degradable flexible material, the required drugs are mixed into the degradable flexible material. The drug type can be selected according to actual needs, and is not limited in this embodiment.

[0091] The substrate 1 includes a microneedle substrate 10 and a microneedle 11. In one embodiment, when the microneedle substrate 10 and the microneedle 11 are made of the same degradable flexible material, the microneedle substrate 10 and the microneedle 11 can be prepared simultaneously during the process of casting and curing to form the substrate 1.

[0092] In another embodiment, when the degradable flexible materials used in the microneedle substrate 10 and the microneedles 11 are different, the degradable flexible material is cast on the surface of the microneedle 11 hole and the elastic mold 7 and cured to form a substrate 1 having the microneedle substrate 10 and a plurality of microneedles 11, comprising:

[0093] like Fig.10 As shown, a first degradable flexible material is poured into the hole of the microneedle 11 and cured to form a plurality of microneedles 11. In a specific embodiment, a degradable flexible material (first degradable flexible material) or a degradable flexible material carrying a drug is covered on the surface of the elastic mold 7, and the degradable flexible material is filled into the hole of the microneedle 11 by vacuuming or centrifugation, and the material on the surface of the elastic mold 7 is scraped off, and heated and cured to form the microneedle 11;

[0094] like Fig.11 As shown, the second degradable flexible material is covered on the elastic mold 7 and cured to form a microneedle substrate 10, and the microneedle substrate 10 and the microneedle 11 are bonded to form a base 1. In a specific embodiment, after the microneedle 11 is formed, another component of the degradable flexible material (the second degradable flexible material) or the degradable flexible material carrying the drug is covered on the surface of the elastic mold 7 by a method such as scraping or glue, and heated and cured to form the microneedle substrate 10. A physical or chemical bond is formed between the microneedle substrate 10 and the microneedle 11 to form a degradable base 1.

[0095] In this embodiment, the dissolution rate of the second degradable flexible material is greater than the dissolution rate of the first degradable flexible material, so that the microneedle substrate 10 can dissolve in a short time after the microneedle array electrode is implanted in the brain, and the bending ability of the microneedle array electrode is better after dissolution, thereby ensuring that the flexible electrode substrate 2 can better fit the cerebral cortex. Since the microneedles 11 are wrapped in the flexible electrode conductive layer 3 and the flexible electrode substrate 2, the drugs carried in the microneedles 11 after implantation can slowly dissolve during the long-term implantation process, thereby achieving slow drug release.

[0096] In the present invention, the drugs include drugs for increasing brain activity and drugs for alleviating side effects after electrodes are implanted in the cerebral cortex, and may be drugs used in other brain science drug research.

[0097] In one embodiment, the thickness of the microneedle substrate 10 is 1 μm-500 μm, the height of the microneedle 11 is 100 μm-5 mm, the bottom diameter of the microneedle 11 is 50 μm-300 μm, and the center distance between adjacent microneedles 11 is 100 μm-1 mm. In one embodiment, the thickness of the flexible electrode substrate 2 is 500 nm-100 μm, the thickness of the flexible electrode conductive layer 3 is 10 nm-10 μm, and the bottom diameter of the electrode point 5 is 5-100 μm.

[0098] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Within the spirit and principle of the present invention, any modification, equivalent replacement, improvement, etc. made shall be included in the protection scope of the present invention.

Claims

1. An implantable soluble microneedle array electrode, characterized in that: include: A substrate, wherein the substrate is a degradable flexible material, and the substrate comprises a microneedle substrate and a plurality of microneedles; A flexible electrode substrate, the flexible electrode substrate covers the microneedle substrate and the microneedles, and the flexible electrode substrate is an insulating material; A flexible electrode conductive layer, wherein the flexible electrode conductive layer covers the surface of the flexible electrode substrate; A flexible electrode insulating layer is arranged on the surface of the flexible electrode conductive layer, and a portion of the flexible electrode conductive layer corresponding to the needle tip of the microneedle is exposed outside the flexible electrode insulating layer to form an electrode point, and the length of the electrode point is less than 100 μm.

2. The implantable soluble microneedle array electrode according to claim 1, characterized in that: The microneedle substrate is made of a different material from that of the microneedles, and the dissolution rate of the microneedle substrate is greater than the dissolution rate of the microneedles.

3. The implantable soluble microneedle array electrode according to claim 1, characterized in that: The bottom diameter of the microneedle is 50 μm-300 μm, and the center distance between adjacent microneedles is 100 μm-1 mm.

4. The implantable soluble microneedle array electrode according to claim 1, characterized in that: The thickness of the flexible electrode substrate is 500nm-100μm, the thickness of the flexible electrode conductive layer is 10nm-10μm, and the bottom diameter of the electrode point is 5-100μm.

5. A method for preparing an implantable soluble microneedle array electrode, characterized in that: The preparation method comprises: Providing an elastic mold, wherein the elastic mold comprises a plurality of micro pinholes; Casting a degradable flexible material on the surface of the microneedle hole and the elastic mold and curing the material to form a substrate having a microneedle substrate and a plurality of microneedles; Peeling the substrate off the elastic mold, and fixing the peeled substrate onto a flat substrate; Growing a flexible electrode substrate on the surface of the microneedle substrate and the microneedles using an insulating material; Growing a metal layer on the surface of the flexible electrode substrate, and patterning the metal layer to form a flexible electrode conductive layer; Growing a flexible electrode insulating layer on the surface of the flexible electrode conductive layer using an insulating material; A window is opened on a portion of the flexible electrode insulating layer corresponding to the needle tip of the microneedle to expose the tip of the flexible electrode conductive layer to form an electrode point, wherein the length of the electrode point is less than 100 μm.

6. The preparation method according to claim 5, characterized in that: The elastic mold is prepared by the following method: Providing a rigid mold, the rigid mold comprising a rigid substrate and a rigid microneedle array disposed on the rigid substrate; Placing the rigid mold in a container, pouring elastic material into the rigid mold and heating and curing it to form the elastic mold; The elastic mold is peeled off from the rigid mold.

7. The preparation method according to claim 5, characterized in that: Before casting the degradable flexible material, the required drugs are mixed into the degradable flexible material.

8. The preparation method according to claim 5, characterized in that: A degradable flexible material is poured on the surface of the microneedle hole and the elastic mold and solidified to form a substrate having a microneedle substrate and a plurality of microneedles, comprising: pouring a first degradable flexible material into the microneedle holes and curing the material to form a plurality of microneedles; Covering the elastic mold with a second degradable flexible material and curing it to form a microneedle substrate, wherein the microneedle substrate and the microneedle are bonded to form the base; The dissolution rate of the second degradable flexible material is greater than the dissolution rate of the first degradable flexible material.

9. The preparation method according to claim 8, characterized in that: The second degradable material carries the desired drug.

10. The preparation method according to claim 5, characterized in that: The thickness of the flexible electrode substrate is 500nm-100μm, the thickness of the flexible electrode conductive layer is 10nm-10μm, and the bottom diameter of the electrode point is 5-100μm.

Images