Hollow electrical stimulation electrode array device and preparation method thereof

Abstract

The invention provides a hollow electrical stimulation electrode array device and a preparation method thereof, and belongs to the technical field of medical instruments, the hollow electrical stimulation electrode array device comprises a substrate and a microneedle array, the substrate comprises a substrate base body, a first conductive lead, a second conductive lead and a substrate insulating layer, the first conductive lead and the second conductive lead are oppositely arranged and are laid on the first surface of the substrate base body at a certain interval; the microneedle array comprises a microneedle array base body, and a hollow channel used as a drug delivery channel is formed in a microneedle base body of the microneedle array base body. An electroporation electrode is improved to be a hollow electrode, medicine in a liquid storage tank can enter intracellular fluid through a hollow channel, the medicine can be injected into a human body through a medicine feeding opening by adopting the hollow electrode, then electroporation is applied to open nanometer through holes of a cell membrane, the medicine enters the intracellular fluid, the steps are simple, the cost is low, and the efficiency is high. The infection risk and the treatment cost of a user are reduced, and due to the design of the liquid storage pool, the functions of medicine storage and injection buffering can be achieved.

Description

Technical Field

[0001] The present application relates to the field of medical device technology, and in particular to a hollow electrical stimulation electrode array device and a preparation method thereof. Background Art

[0002] For some macromolecular drugs such as nucleic acids or plasmids, the drugs need to enter the intracellular fluid to exert their effects. Limited by the selective permeability of the cell membrane, these drugs are difficult to directly pass through the cell membrane into the intracellular fluid, and require the use of external methods to assist the drugs to efficiently enter the intracellular fluid. Electroporation technology is a commonly used method to assist drugs to enter cells. Its principle is to use electric pulses to instantaneously open the cell membrane and then produce instantaneous nanopores. These nanopores allow macromolecular drugs such as nucleic acids to diffuse into the intracellular fluid with the help of the concentration difference between the inside and outside of the cell membrane to exert their effects. After the external electric pulse (electric field) is removed, the nanopores on the cell membrane surface are restored.

[0003] Currently, the electrodes used for electroporation are usually solid electrodes. When using solid electrodes for electroporation research, it is necessary to use a disposable syringe to inject a large molecule drug solution such as nucleic acid into the subcutaneous tissue in advance, and then use a solid electroporation electrode to perform electroporation. Drug injection and electroporation delivery need to be performed in steps, which increases the infection risk and treatment cost of the user and is cumbersome to operate. Summary of the invention

[0004] The purpose of the present application is to provide a hollow electrical stimulation electrode array device and a preparation method thereof, aiming to solve the problem that when solid electrodes are used for electroporation in the related art, drug injection is required in advance and then electroporation delivery is performed, which increases the infection risk and treatment cost of the user and is cumbersome to operate.

[0005] Additional aspects and advantages of the present application will be set forth in part in the description which follows and, in part, will be obvious from the description, or may be learned by practice of the present application.

[0006] According to a first aspect of the present application, a hollow electrical stimulation electrode array device is provided, comprising a substrate and a microneedle array, wherein the substrate comprises a substrate base, a first conductive lead, a second conductive lead and a substrate insulating layer, wherein the first conductive lead and the second conductive lead are arranged opposite to each other and laid on a first surface of the substrate base at a certain interval, wherein the substrate insulating layer covers an area on the first surface except for the first conductive lead and the second conductive lead, wherein a liquid reservoir is formed inside the substrate base, and a drug delivery port connected to the liquid reservoir is also provided on the substrate base, wherein one of the first conductive lead and the second conductive lead is suitable for connecting to a positive electrode of a stimulation power source, and the other is suitable for connecting to a negative electrode of the stimulation power source;

[0007] The microneedle array comprises a microneedle array substrate, a microneedle array conductive layer, and a microneedle array insulating layer. The microneedle array substrate is arranged on the first conductive lead and the second conductive lead. The microneedle array conductive layer covers the microneedle array substrate and is electrically connected to the corresponding first conductive lead and the second conductive lead. The microneedle array insulating layer covers the area on the microneedle array conductive layer except the tip of the microneedle substrate. The microneedle substrate of the microneedle array substrate is provided with a hollow channel used as a drug delivery channel. One end of the hollow channel is opened on the tip surface of the microneedle substrate, and the other end is opened to connect to the liquid reservoir.

[0008] In an exemplary embodiment of the present application, the first conductive lead includes a plurality of first conductive branches arranged in parallel and a first connecting lead for electrically connecting the plurality of first conductive branches, the second conductive lead includes a plurality of second conductive branches arranged in parallel and a second connecting lead for electrically connecting the plurality of second conductive branches, the microneedle array substrate is arranged on the plurality of first conductive branches and the plurality of second conductive branches, the plurality of first conductive branches are parallel to and staggered with the plurality of second conductive branches, and the intervals between adjacent first conductive branches and second conductive branches are equal.

[0009] In an exemplary embodiment of the present application, the first conductive lead also includes a first lead end connected to any one of the first conductive branches or the first connecting lead, and the second conductive lead also includes a second lead end connected to any one of the second conductive branches or the second connecting lead, and one of the first lead end and the second lead end is suitable for connecting to the positive pole of the stimulation power supply, and the other is suitable for connecting to the negative pole of the stimulation power supply.

[0010] In an exemplary embodiment of the present application, the first conductive lead and the second conductive lead are both bent serpentine structures, and the two bent serpentine structures are arranged opposite to each other and are equidistant from each other.

[0011] In an exemplary embodiment of the present application, the end of the hollow channel communicating with the liquid reservoir has an opening, and the opening gradually increases in size from the microneedle substrate to the liquid reservoir.

[0012] In an exemplary embodiment of the present application, the drug delivery port is opened on a second surface of the substrate base opposite to the first surface, and the drug delivery port is connected to the liquid storage tank.

[0013] According to a second aspect of the present application, a method for preparing a hollow electrical stimulation electrode array device is provided, comprising the following steps:

[0014] Processing an electrode matrix, the electrode matrix comprising a substrate matrix and a microneedle array matrix located on a first surface of the substrate matrix, each microneedle matrix in the microneedle array matrix has a hollow channel inside, the substrate matrix is ​​provided with a liquid reservoir inside, one end of the hollow channel is opened on the tip surface of the microneedle matrix, and the other end is opened to connect to the liquid reservoir, and the substrate matrix is ​​also provided with a drug delivery port connected to the liquid reservoir;

[0015] Depositing a conductive layer, covering the first mask plate with a hollowed-out conductive layer deposition area on the first surface of the substrate base, allowing the microneedle array base to pass through the hollowed-out portion of the first mask plate, depositing a conductive layer on the unshielded portion of the first mask plate, removing the first mask plate after the deposition is completed, forming a microneedle array conductive layer on the unshielded portion of the microneedle array base of the first mask plate, and forming a first conductive lead and a second conductive lead on the substrate base, wherein the first conductive lead and the second conductive lead are insulated from each other and are electrically connected to their corresponding microneedle array conductive layers respectively;

[0016] Deposit an insulating layer, cover the tip of the microneedle array substrate with a second mask, insert the tip of the microneedle array substrate into the second mask, deposit an insulating layer on the unshielded portion of the second mask, and remove the second mask after deposition is completed.

[0017] In an exemplary embodiment of the present application, in the step of depositing the conductive layer, the conductive layer deposited on the unshielded portion of the first mask plate is a conductive thin layer serving as a subsequent electroplating seed layer; the step of depositing the conductive layer also includes placing the microneedle array electrode on which the surface conductive thin layer deposition has been completed into the electroplating solution, connecting the first conductive lead and the second conductive lead to the cathode of the power supply device, connecting the anode of the power supply device to the plated metal electrode or the inert electrode, and electroplating a thicker conductive layer on the surface of the conductive thin layer, and finally the thickness of the conductive layer is 2-10μm.

[0018] In an exemplary embodiment of the present application, in the step of depositing an insulating layer, it also includes: using a third mask plate to cover the first conductive lead and the stimulation power supply connection area, using a fourth mask plate to cover the second conductive lead and the stimulation power supply connection area, covering the unshielded parts of the third mask plate and the fourth mask plate with an insulating layer, and removing the third mask plate and the fourth mask plate after the deposition is completed.

[0019] In an exemplary embodiment of the present application, in the step of processing the electrode substrate, an integrated electrode substrate is produced by 3D printing.

[0020] The exemplary embodiments of the present application may have some or all of the following beneficial effects:

[0021] The hollow electrical stimulation electrode array device provided in the exemplary embodiment of the present application includes a substrate and a microneedle array, the substrate includes a substrate base, a first conductive lead, a second conductive lead and a substrate insulating layer, the first conductive lead and the second conductive lead are arranged opposite to each other and laid on the first surface of the substrate base with a certain interval, the substrate insulating layer covers the area on the first surface except the first conductive lead and the second conductive lead, a liquid reservoir is formed inside the substrate base, and a drug delivery port connected to the liquid reservoir is opened on the substrate base, one of the first conductive lead and the second conductive lead is used to connect the positive electrode of the stimulation power supply, and the other is used to connect the negative electrode of the stimulation power supply. In this embodiment, the first conductive lead and the second conductive lead are connected to the positive electrode of the stimulation power supply. The conductive lead is connected to the positive electrode of the stimulation power supply, and the second conductive lead is connected to the negative electrode of the stimulation power supply; the microneedle array includes a microneedle array substrate, a microneedle array conductive layer, and a microneedle array insulating layer. The microneedle array substrate is arranged on the first conductive lead and the second conductive lead, the microneedle array conductive layer covers the microneedle array substrate and is electrically connected to the corresponding first conductive lead and the second conductive lead, the microneedle array insulating layer covers the area on the microneedle array conductive layer except the tip of the microneedle substrate, and the microneedle substrate of the microneedle array substrate is provided with a hollow channel for serving as a drug delivery channel, one end of the hollow channel is opened on the tip surface of the microneedle substrate, and the other end is opened to connect to the liquid storage tank.

[0022] On the one hand, a hollow channel is formed in the microneedle matrix, one end of the hollow channel opens on the tip surface of the microneedle matrix, and the other end opens to connect to a reservoir, which can store drugs. The operator can deliver the drugs to the reservoir through the drug delivery port, and the electroporation electrode is improved to a hollow electrode, the interior of the hollow electrode can accommodate drug solution, the drug is first injected into the body, and then electroporation is applied to open the nanopores of the cell membrane, the drug in the reservoir can enter the intracellular fluid through the hollow channel, there is no need to pre-inject macromolecular drug solutions such as nucleic acids into the subcutaneous tissue, and then use a solid electroporation electrode to apply electroporation, the use of hollow electrodes is simple, reduces the infection risk and treatment cost of users, and is simple to operate; at the same time, the design of the reservoir can realize the functions of drug storage and injection buffering.

[0023] On the other hand, the first conductive lead and the second conductive lead on the substrate base are respectively connected to the positive electrode and the negative electrode of the stimulation power supply, and the first conductive lead and the second conductive lead are both arranged on the first surface of the substrate base, and the first conductive lead and the second conductive lead are arranged oppositely and at intervals, so that a positive electrode and a negative electrode are formed between the first conductive lead and the second conductive lead, and the microneedle array substrate located on the first conductive lead and the second conductive lead forms a positive electrode or a negative electrode corresponding to it on each lead. After the hollow electrical stimulation electrode array device is implanted in the tissue, the first conductive lead and the second conductive lead are connected to the stimulation power supply, and the microneedle substrate on the first conductive lead and the microneedle substrate on the second conductive lead are connected to the stimulation power supply. The microneedle matrix forms a circuit path through the tissue itself and the tissue fluid, and electroporates the cells around the microneedle matrix. A first conductive lead and a second conductive lead connected to the positive and negative electrodes of the stimulation power source are respectively arranged on the substrate matrix, thereby avoiding the need to implant one of the electrodes into the tissue in advance to form a circuit path with the electrical stimulation electrode array device to electroporate the cells in the tissue. The hollow electrical stimulation electrode array device provided in this embodiment only needs to be implanted into the tissue and connected to the stimulation power source to form a circuit path between the microneedle matrices and electroporate the cells around the microneedle matrix, thereby reducing the infection risk of the user and facilitating operation.

[0024] It should be understood that the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the present application. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] The drawings herein are incorporated into the specification and constitute a part of the specification, illustrate embodiments consistent with the present application, and together with the specification are used to explain the principles of the present application. Obviously, the drawings described below are only some embodiments of the present application, and for ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0026] Figure 1 A schematic diagram of the structure of a hollow electrical stimulation electrode array device at a first angle in Example 1 of the present application is shown;

[0027] Figure 2 A second angle structural schematic diagram of a hollow electrical stimulation electrode array device in Example 1 of the present application is shown;

[0028] Figure 3 A cross-sectional view of a hollow electrical stimulation electrode array device in Example 1 of the present application is shown;

[0029] Figure 4 The schematic diagram of the structure of the microneedle substrate in Example 1 of the present application is shown;

[0030] Figure 5 Shows Figure 4Enlarged view of point A in the middle;

[0031] Figure 6 A schematic diagram showing the structure of the hollow electrical stimulation electrode array device connected to a flexible circuit board in Example 1 of the present application is shown;

[0032] Figure 7 A schematic diagram of the structure of the hollow electrical stimulation electrode array device connected to the infusion hose at a first angle in Example 1 of the present application is shown;

[0033] Figure 8 A second angle structural schematic diagram of the hollow electrical stimulation electrode array device connected to the infusion hose in Example 1 of the present application is shown;

[0034] Fig. 9 A schematic diagram of the first angle structure of the electrode substrate in Example 2 of the present application is shown;

[0035] Fig.10 A second angle structural schematic diagram of the electrode substrate in Example 2 of the present application is shown;

[0036] Fig.11 A third angle structural schematic diagram of the electrode substrate in Example 2 of the present application is shown;

[0037] Fig.12 A schematic diagram of the structure of the first mask plate in Embodiment 2 of the present application is shown;

[0038] Fig.13 A schematic diagram of the structure in which the first mask plate covers the electrode substrate in Example 2 of the present application is shown;

[0039] Fig.14 A schematic diagram of the structure of an electrode substrate on which a first conductive lead and a second conductive lead are deposited in Example 2 of the present application is shown;

[0040] Fig.15 A schematic diagram of the structure of covering the second mask plate, the third mask plate, and the fourth mask plate in Embodiment 2 of the present application is shown;

[0041] Fig.16 A side view of the second mask plate, the third mask plate, and the fourth mask plate in Embodiment 2 of the present application is shown.

[0042] Description of reference numerals:

[0043] 001, the first mask plate; 002, the second mask plate; 003, the third mask plate; 004, the fourth mask plate;

[0044] 11. substrate matrix; 12. microneedle matrix; 121. microneedle matrix tip; 122. microneedle array conductive layer; 123. microneedle array insulating layer; 13. hollow channel; 131. hollow channel conductive layer; 132. hollow channel insulating layer; 14. liquid reservoir; 15. drug delivery port; 21. first conductive lead; 22. second conductive lead; 23. first lead end; 24. flexible circuit board; 25. second lead end; 31. infusion hose. DETAILED DESCRIPTION

[0045] Example embodiments will now be described more fully with reference to the accompanying drawings. However, the example embodiments can be implemented in a variety of forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that the present application will be comprehensive and complete and fully convey the concepts of the example embodiments to those skilled in the art. The same reference numerals in the figures represent the same or similar structures, and thus their detailed descriptions will be omitted. In addition, the drawings are only schematic illustrations of the present application and are not necessarily drawn to scale.

[0046] Although relative terms such as "upper" and "lower" are used in this specification to describe the relative relationship of one component of the diagram to another component, these terms are used in this specification only for convenience, such as according to the direction of the examples in the drawings. It is understood that if the device of the diagram is turned upside down, the component described as "upper" will become the component "lower". When a structure is "on" other structures, it may mean that the structure is formed integrally on the other structure, or that the structure is "directly" disposed on the other structure, or that the structure is "indirectly" disposed on the other structure through another structure.

[0047] The terms "a", "an", "the" and "at least one" are used to indicate the presence of one or more elements / components / etc.; the terms "including" and "having" are used to express an open-ended inclusive meaning and mean that additional elements / components / etc. may exist in addition to the listed elements / components / etc.; the terms "first" and "second" are used merely as labels and are not intended to limit the quantity of their objects.

[0048] Example 1

[0049] The present application embodiment provides a specific implementation of a hollow electrical stimulation electrode array device, such as Figure 1 , Figure 2 and Figure 3As shown, it includes a substrate and a microneedle array, the substrate includes a substrate base 11, a first conductive lead 21, a second conductive lead 22 and a substrate insulating layer, the first conductive lead 21 and the second conductive lead 22 are arranged opposite to each other and laid on the first surface of the substrate base 11 with a certain interval, the substrate insulating layer covers the area on the first surface except the first conductive lead 21 and the second conductive lead 22, a liquid reservoir 14 is formed inside the substrate base 11, and a drug delivery port 15 connected to the liquid reservoir 14 is opened on the substrate base 11, one of the first conductive lead 21 and the second conductive lead 22 is used to connect the positive electrode of the stimulation power supply, and the other is used to connect the negative electrode of the stimulation power supply. In this embodiment, the first conductive lead 21 is connected to the positive electrode of the stimulation power supply. , the second conductive lead 22 is connected to the negative electrode of the stimulation power supply; the microneedle array includes a microneedle array substrate, a microneedle array conductive layer 122, and a microneedle array insulating layer 123. The microneedle array substrate is arranged on the first conductive lead 21 and the second conductive lead 22. The microneedle array conductive layer 122 covers the microneedle array substrate and is electrically connected to the corresponding first conductive lead 21 and the second conductive lead 22. The microneedle array insulating layer 123 covers the area on the microneedle array conductive layer 122 except the tip of the microneedle substrate 12. The microneedle substrate 12 of the microneedle array substrate is provided with a hollow channel 13 for serving as a drug delivery channel. One end of the hollow channel 13 is opened on the tip surface of the microneedle substrate 12, and the other end is opened to connect to the liquid reservoir 14.

[0050] The hollow electrical stimulation electrode array device provided in the present embodiment, on the one hand, forms a hollow channel 13 on the microneedle matrix 12, one end of the hollow channel 13 is opened on the tip surface of the microneedle matrix 12, and the other end is opened to connect to the reservoir 14, the reservoir 14 can store drugs, and the operator can deliver the drugs to the reservoir 14 through the drug delivery port 15, and the electroporation electrode is improved to a hollow electrode. When electroporation is applied, the drugs in the reservoir 14 can enter the body through the hollow channel 13, and there is no need to inject a macromolecular drug solution such as nucleic acid into the subcutaneous tissue in advance, and then use a solid electroporation electrode to apply electroporation. The hollow electrode can be used to first inject the drug into the body through the drug delivery port 15, and then electroporation is applied to open the nanopores of the cell membrane, and the drug flows into the intracellular fluid through the hollow channel 13. The steps are simple, the infection risk and treatment cost of the user are reduced, and the operation is simple; at the same time, the design of the reservoir 14 can realize the functions of drug storage and injection buffering.

[0051] On the other hand, the first conductive lead 21 and the second conductive lead 22 on the substrate base 11 are respectively connected to the positive electrode and the negative electrode of the stimulation power supply, and the first conductive lead 21 and the second conductive lead 22 are both arranged on the first surface of the substrate base 11, and the first conductive lead 21 and the second conductive lead 22 are arranged opposite to each other and spaced apart, so that a positive electrode and a negative electrode are formed between the first conductive lead 21 and the second conductive lead 22, and the microneedle array substrates located on the first conductive lead 21 and the second conductive lead 22 form a positive electrode or a negative electrode corresponding to them on their respective leads. After the hollow electrical stimulation electrode array device is implanted in the tissue, the first conductive lead 21 and the second conductive lead 22 are connected to the stimulation power supply, and the microneedle substrate 12 on the first conductive lead 21 The microneedle matrix 12 on the second conductive lead 22 forms a circuit path through the tissue itself and the tissue fluid, and electroporates the cells around the microneedle matrix 12. The first conductive lead 21 and the second conductive lead 22 connected to the positive and negative poles of the stimulation power source are respectively arranged on the substrate matrix 11, which avoids the need to implant one of the electrodes into the tissue in advance to form a circuit path with the electrical stimulation electrode array device to electroporate the cells in the tissue. The hollow electrical stimulation electrode array device provided in this embodiment only needs to be implanted into the tissue and connected to the stimulation power source to form a circuit path between the microneedle matrix 12 and electroporate the cells around the microneedle matrix 12, thereby reducing the infection risk of the user and facilitating operation.

[0052] In this embodiment, Figure 4 and Figure 5 As shown, the preferred dimensions of the microneedle matrix 12 are: height 500-2000 μm, bottom diameter 100-1000 μm, top diameter 5-60 μm, the center distance between adjacent microneedle matrixes 12 is preferably 300-2000 μm, the size of the substrate matrix 11 is determined by the number and arrangement of the microneedle array matrix and the electrode interconnection structure, preferably 1 mm×1 mm to 20 mm×20 mm, the size of the hollow channel 13 in the microneedle matrix 12 is limited by the size of the microneedle matrix 12, and the side wall thickness between the hollow channel 13 and the microneedle matrix 12 is preferably 20-400 μm.

[0053] Furthermore, the microneedle array conductive layer 122 is made of a conductive material with high conductivity, high biocompatibility, and stable electrochemical performance, including but not limited to nickel, gold, and platinum. The substrate insulating layer is made of an insulating material with high biocompatibility, including but not limited to polyparaxylene, polyimide, polyurethane, and polytetrafluoroethylene.

[0054] In the present embodiment, a microneedle array substrate is laid on the first surface of the substrate base 11, which may also be referred to as a microneedle surface, and other surfaces without the microneedle array substrate are non-microneedle surfaces. Specifically, the substrate insulating layer covers the area on the microneedle surface except for the first conductive lead 21 and the second conductive lead 22. Such a design can reduce the overall thickness of the electrical stimulation electrode array device, reduce the bending stiffness of the electrical stimulation electrode array device, and improve the electrode flexibility. In some other embodiments, the substrate insulating layer may also cover the non-microneedle surface of the substrate base 11, so that the electrical stimulation electrode array device does not separate from the layers when it is immersed in tissue fluid for a long time, thereby ensuring the structural stability of the electrical stimulation electrode array device during long-term implantation.

[0055] In this embodiment, the first conductive lead 21 includes a plurality of first conductive branches arranged in parallel and a first connecting lead for electrically connecting the plurality of first conductive branches, the second conductive lead 22 includes a plurality of second conductive branches arranged in parallel and a second conductive lead 22 for electrically connecting the plurality of second conductive branches, and the microneedle array substrate is arranged on the plurality of first conductive branches and the plurality of second conductive branches, wherein the plurality of first conductive branches and the plurality of second conductive branches are arranged in parallel and staggered, and the intervals between adjacent first conductive branches and second conductive branches are equal.

[0056] In this embodiment, the first conductive branch line and the second conductive branch line are preferably parallel straight lines to facilitate better arrangement of the microneedle array substrate; in some other embodiments, the first conductive lead 21 and the second conductive lead 22 can also be set as a bent serpentine structure. As long as the two bent serpentine structures are arranged relative to each other and are equally spaced, and their conductive branches are staggered and equally spaced, there is no specific restriction on their specific shape.

[0057] Furthermore, the first conductive lead 21 also includes a first lead end 23 connected to any one of the first conductive branches or the first connecting lead, and the second conductive lead 22 also includes a second lead end 25 connected to any one of the second conductive branches or the second connecting lead. One of the first lead end 23 and the second lead end 25 is used to connect to the positive pole of the stimulation power supply, and the other is used to connect to the negative pole of the stimulation power supply. In this embodiment, the first lead end 23 is connected to the positive pole of the stimulation power supply, and the second lead end 25 is connected to the negative pole of the stimulation power supply; in some other embodiments, the first lead end 23 may be connected to the negative pole of the stimulation power supply, and the second lead end 25 may be connected to the positive pole of the stimulation power supply. There is no specific limitation on this, and the operator can make a selection according to actual conditions.

[0058] Furthermore, if Figure 6 , Figure 7 and Figure 8As shown, the first conductive lead 21 is connected to the flexible circuit board 24 through the first lead end 23, and the second conductive lead 22 is connected to the flexible circuit board 24 through the second lead end 25. Through the flexible circuit board 24, the first conductive lead 21 and the second conductive lead 22 are respectively connected to the positive and negative electrodes of the stimulation power supply; the first lead end 23 and the second lead end 25 are both silver pastes. In some other embodiments, the first lead end 23 and the second lead end 25 can also be conductive adhesives such as solder and conductive paste; the flexible circuit board 24 can be replaced by conductive leads such as DuPont wires and metal wires, and the area not covered by the insulating layer in the hollow electrical stimulation electrode array device can also be connected to the positive and negative output interfaces of the stimulation power supply.

[0059] In this embodiment, the opening position where the hollow channel 13 is connected to the liquid reservoir 14 has an opening, and the opening gradually increases from the direction of the microneedle matrix 12 to the liquid reservoir 14, forming a trumpet shape, so that the drug in the liquid reservoir 14 can flow into the hollow channel 13 through the trumpet-shaped opening. Further, the inner surface of the hollow channel 13 is also covered with a hollow channel conductive layer 131 of a certain depth, and the microneedle array conductive layer 122 and the hollow channel conductive layer 131 are connected to the conductive lead of the substrate matrix 11; the inner surface of the hollow channel 13 is provided with a hollow channel insulating layer 132, and only the microneedle matrix tip 121 is exposed for several microns to tens of microns, and the size of the exposed area of ​​the microneedle matrix tip 121 can be adjusted according to the actual stimulation range and stimulation effect.

[0060] In this embodiment, the drug delivery port 15 is provided on the second surface of the substrate base 11 opposite to the first surface, and the drug delivery port 15 is connected to the liquid reservoir 14, and the drug delivery port 15 is used to deliver the drug to the liquid reservoir 14. The drug delivery port 15 is provided on the second surface of the substrate base 11, and after the hollow electrical stimulation electrode array device is implanted in the tissue, the first surface penetrates the tissue, and the second surface is exposed to the outside, and the drug delivery port 15 can be used to continuously deliver the drug to the liquid reservoir 14. The drug delivery port 15 can be connected to the infusion hose 31, and the operator injects the drug into the liquid reservoir 14 through the infusion hose 31, and the infusion hose 31 can also be replaced by other pipes that can be used for drug injection.

[0061] In this embodiment, the shape of the substrate matrix 11 is not limited to a square, and can be any shape, as long as the drug injection and electrode lead-out functions can be achieved through the hollow channel 13; the shape of the microneedle matrix 12 is not limited to a cone, and can be customized to any shape, as long as it can penetrate the skin and a hollow channel 13 can be set inside the microneedle array for drug injection; the number of microneedle matrices 12 contained in the microneedle array matrix is ​​not limited, as long as it can be divided into two arrays to which positive and negative voltages are applied simultaneously; the shape of the hollow channel 13 is not limited to a cylinder, as long as a drug delivery passage can be formed, and the number of hollow channels 13 corresponds to the number of microneedle matrices 12; the shape of the liquid reservoir 14 is not limited to a square, and can be customized to any shape, as long as the injection buffer function of the drug storage box can be achieved; the shape of the drug delivery port 15 is not limited to a circle, and can be customized to any shape, as long as it is opened on the non-microneedle surface of the substrate matrix 11 and is connected to the liquid reservoir 14 and the hollow channel 13 to achieve the drug injection function, and at the same time, the number of drug delivery ports 15 is not limited to one.

[0062] Example 2

[0063] This embodiment provides a specific implementation method of a method for preparing a hollow electrical stimulation electrode array device. The preparation of the hollow electrical stimulation electrode array device in Example 1 includes the following steps:

[0064] Processing the electrode substrate, such as Fig. 9 , Fig.10 and Fig.11 As shown, the electrode matrix includes a substrate matrix 11 and a microneedle array matrix located on the first surface of the substrate matrix 11, each microneedle matrix 12 in the microneedle array matrix has a hollow channel 13 inside, and a liquid reservoir 14 is provided inside the substrate matrix 11, one end of the hollow channel 13 is opened on the tip surface of the microneedle matrix 12, and the other end is opened to connect to the liquid reservoir 14, and a drug delivery port 15 connected to the liquid reservoir 14 is also provided on the substrate matrix;

[0065] Deposition of conductive layers, such as Fig.12 , Fig.13 and Fig.14 As shown, the first mask plate 001 with a hollowed-out conductive layer deposition area is covered on the first surface of the substrate base 11, so that the microneedle array substrate passes through the hollowed-out portion of the first mask plate 001, and the conductive layer is deposited on the unblocked portion of the first mask plate 001. After the deposition is completed, the first mask plate 001 is removed, and a microneedle array conductive layer 122 is formed on the unblocked portion of the microneedle array substrate of the first mask plate 001, and a first conductive lead 21 and a second conductive lead 22 are formed on the substrate base 11. The first conductive lead 21 and the second conductive lead 22 are insulated from each other and are electrically connected to the corresponding microneedle array conductive layer 122 respectively; further, a vacuum coating process is used when depositing the conductive layer.

[0066] Deposition of insulating layers, such as Fig.15 As shown, the second mask plate is covered on the tip of the microneedle array substrate, and the tip of the microneedle array substrate penetrates into the second mask plate, and an insulating layer is deposited on the unshielded portion of the second mask plate. After the deposition is completed, the second mask plate is removed to form a substrate insulating layer.

[0067] In this embodiment, the second mask plate is preferably an elastic mask plate.

[0068] In this embodiment, in the step of depositing a conductive layer, the conductive layer deposited on the unshielded portion of the first mask plate 001 is used as a conductive thin layer for a subsequent electroplating seed layer. The step of depositing a conductive layer also includes placing the microneedle array electrode on which the surface conductive thin layer has been deposited into an electroplating solution, connecting the first conductive lead 21 and the second conductive lead 22 to the cathode of a power supply device, and connecting the anode of the power supply device to a plated metal electrode or an inert electrode, and electroplating a thicker conductive layer on the surface of the conductive thin layer. The final thickness of the conductive layer is 2-10 μm.

[0069] In this embodiment, in the step of depositing the insulating layer, Fig.15 and Fig.16 As shown, it also includes using a third mask plate 003 to cover the first conductive lead 21 and the stimulation power supply connection area, using a fourth mask plate 004 to cover the second conductive lead 22 and the stimulation power supply connection area, covering the unshielded parts of the third mask plate 003 and the fourth mask plate 004 with an insulating layer, and removing the third mask plate 003 and the fourth mask plate 004 after deposition is completed.

[0070] In this embodiment, in the step of processing the electrode substrate, an integrated electrode substrate is produced by 3D printing.

[0071] Those skilled in the art will easily think of other embodiments of the present application after considering the specification and practicing the embodiments of the present application. The present application is intended to cover any modification, use or adaptation of the present application, which follows the general principles of the present application and includes common knowledge or customary techniques in the art that the present application does not apply for. The specification and embodiments are only regarded as exemplary, and the true scope and spirit of the present application are pointed out by the appended claims.

Claims

1. A hollow electrical stimulation electrode array device, comprising a substrate and a microneedle array, characterized in that: The substrate comprises a substrate base, a first conductive lead, a second conductive lead and a substrate insulating layer, the first conductive lead and the second conductive lead are arranged opposite to each other and laid on the first surface of the substrate base at a certain interval, the substrate insulating layer covers the area on the first surface except the first conductive lead and the second conductive lead, a liquid reservoir is formed inside the substrate base, and a drug delivery port connected to the liquid reservoir is also opened on the substrate base, one of the first conductive lead and the second conductive lead is suitable for connecting the positive electrode of the stimulation power supply, and the other is suitable for connecting the negative electrode of the stimulation power supply; The microneedle array comprises a microneedle array substrate, a microneedle array conductive layer, and a microneedle array insulating layer. The microneedle array substrate is arranged on the first conductive lead and the second conductive lead. The microneedle array conductive layer covers the microneedle array substrate and is electrically connected to the corresponding first conductive lead and the second conductive lead. The microneedle array insulating layer covers the area on the microneedle array conductive layer except the tip of the microneedle substrate. The microneedle substrate of the microneedle array substrate is provided with a hollow channel used as a drug delivery channel. One end of the hollow channel is opened on the tip surface of the microneedle substrate, and the other end is opened to connect to the liquid reservoir.

2. The hollow electrical stimulation electrode array device according to claim 1, characterized in that: The first conductive lead includes a plurality of first conductive branches arranged in parallel and a first connecting lead for electrically connecting the plurality of first conductive branches, the second conductive lead includes a plurality of second conductive branches arranged in parallel and a second connecting lead for electrically connecting the plurality of second conductive branches, the microneedle array substrate is arranged on the plurality of first conductive branches and the plurality of second conductive branches, the plurality of first conductive branches are parallel to and staggered with the plurality of second conductive branches, and the intervals between adjacent first conductive branches and second conductive branches are equal.

3. The hollow electrical stimulation electrode array device according to claim 2, characterized in that: The first conductive lead also includes a first lead end connected to any one of the first conductive branches or the first connecting lead, and the second conductive lead also includes a second lead end connected to any one of the second conductive branches or the second connecting lead, one of the first lead end and the second lead end is suitable for connecting to the positive pole of the stimulation power supply, and the other is suitable for connecting to the negative pole of the stimulation power supply.

4. The hollow electrical stimulation electrode array device according to claim 1, characterized in that: The first conductive lead and the second conductive lead are both bent serpentine structures, and the two bent serpentine structures are arranged opposite to each other and are equidistant from each other.

5. The hollow electrical stimulation electrode array device according to claim 1, characterized in that: The end of the hollow channel communicating with the liquid reservoir has an opening, and the opening gradually increases in size from the microneedle substrate to the liquid reservoir.

6. The hollow electrical stimulation electrode array device according to claim 1, characterized in that: The drug delivery port is opened on a second surface of the substrate base body opposite to the first surface, and the drug delivery port is communicated with the liquid storage tank.

7. A method for preparing a hollow electrical stimulation electrode array device, characterized in that: The following steps are involved: Processing an electrode matrix, the electrode matrix comprising a substrate matrix and a microneedle array matrix located on a first surface of the substrate matrix, each microneedle matrix in the microneedle array matrix has a hollow channel inside, the substrate matrix is ​​provided with a liquid reservoir inside, one end of the hollow channel is opened on the tip surface of the microneedle matrix, and the other end is opened to connect to the liquid reservoir, and the substrate matrix is ​​also provided with a drug delivery port connected to the liquid reservoir; Depositing a conductive layer, covering the first mask plate with a hollowed-out conductive layer deposition area on the first surface of the substrate base, allowing the microneedle array base to pass through the hollowed-out portion of the first mask plate, depositing a conductive layer on the unshielded portion of the first mask plate, removing the first mask plate after the deposition is completed, forming a microneedle array conductive layer on the unshielded portion of the microneedle array base of the first mask plate, and forming a first conductive lead and a second conductive lead on the substrate base, wherein the first conductive lead and the second conductive lead are insulated from each other and are electrically connected to their corresponding microneedle array conductive layers respectively; Deposit an insulating layer, cover the tip of the microneedle array substrate with a second mask, insert the tip of the microneedle array substrate into the second mask, deposit an insulating layer on the unshielded portion of the second mask, and remove the second mask after deposition is completed.

8. The method for preparing a hollow electrical stimulation electrode array device according to claim 7, characterized in that: In the step of depositing the conductive layer, the conductive layer deposited on the unshielded part of the first mask plate is a conductive thin layer used as a subsequent electroplating seed layer; the step of depositing the conductive layer also includes placing the microneedle array electrode on which the surface conductive thin layer deposition is completed into the electroplating solution, connecting the first conductive lead and the second conductive lead to the cathode of the power supply device, connecting the anode of the power supply device to the plated metal electrode or the inert electrode, and electroplating a thicker conductive layer on the surface of the conductive thin layer, and finally the thickness of the conductive layer is 2-10μm.

9. The method for preparing a hollow electrical stimulation electrode array device according to claim 7, characterized in that: The step of depositing an insulating layer also includes: using a third mask plate to cover the area where the first conductive lead is connected to the stimulation power supply, using a fourth mask plate to cover the area where the second conductive lead is connected to the stimulation power supply, covering the unshielded parts of the third mask plate and the fourth mask plate with an insulating layer, and removing the third mask plate and the fourth mask plate after the deposition is completed.

10. The method for preparing a hollow electrical stimulation electrode array device according to claim 7, characterized in that: In the step of processing the electrode substrate, an integrated electrode substrate is produced by 3D printing.

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