A flexible hollow electrostimulation electrode array device and its fabrication method

Abstract

This application provides a flexible hollow electrostimulation electrode array device and its preparation method, belonging to the field of medical device technology. Specifically, it includes a flexible substrate and a microneedle array; the microneedle array includes multiple microneedles, at least some of which have different heights; the leads of the microneedles are used for electrical connection to a detection device and an electrical pulse generator. When it is necessary to use electroporation to allow macromolecular drugs to enter the intracellular fluid, the flexible hollow electrostimulation electrode array device is implanted into human tissue. Microneedles of different heights penetrate into different depths within the tissue. The leads of the microneedles are first connected to a detection device to detect the neurophysiological signals of the target brain region to determine the location and type of the disease. Then, an electrical pulse generator is connected to provide pulsed current to the microneedles, enabling macromolecular drugs to enter the intracellular fluid through the nanopores of the cell membrane via electroporation for treatment of the lesion. After a period of treatment, the detection device is connected again to assess the treatment effect.

Description

Technical Field

[0001] This application relates to the field of medical device technology, and more specifically, to a flexible hollow electrical stimulation electrode array device and its preparation method. Background Technology

[0002] For certain macromolecular drugs such as nucleic acids or plasmids, the drugs need to enter the intracellular fluid to exert their effects. Due to the selective permeability of the cell membrane, these drugs cannot directly enter the intracellular fluid through the cell membrane and require external methods to assist in the efficient entry of drugs into the intracellular fluid. Electroporation is a commonly used method to assist in the entry of drugs into cells. Its principle is to use an electric pulse to momentarily open the cell membrane, thereby creating transient nanopores. These nanopores allow macromolecular drugs such as nucleic acids to diffuse into the intracellular fluid by means of the concentration difference across 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] For certain neurological diseases, a detection electrode needs to be implanted to detect the lesion before electroporation, and then an electroporation electrode needs to be implanted to electroporate the lesion. This method requires two punctures into the lesion, which can easily cause puncture damage to the patient's lesion. Summary of the Invention

[0004] The purpose of this application is to provide a flexible hollow electrostimulation electrode array device and its preparation method, which aims to solve the problem in related technologies that require the implantation of detection electrodes first and then electroporation electrodes, requiring two punctures into the lesion site, which can easily cause puncture damage to the patient's lesion site.

[0005] Additional aspects and advantages of this 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 this application.

[0006] According to a first aspect of this application, a flexible hollow electrical stimulation electrode array device is provided, comprising a flexible substrate and a microneedle array.

[0007] The flexible substrate is provided with a drug delivery channel;

[0008] The microneedle array is disposed on the flexible substrate, and the microneedle array includes multiple microneedles, at least some of which have different heights, so that the microneedles can penetrate into the tissue to different depths.

[0009] The lead end of the microneedle is used for electrical connection with the detection equipment and the electrical pulse generator;

[0010] The microneedle has a hollow channel, with one end of the hollow channel opening at the tip of the microneedle and the other end opening connected to the drug delivery channel.

[0011] In one exemplary embodiment of this application, a plurality of independent conductive leads are disposed on the flexible substrate, and the plurality of conductive leads are electrically connected to the lead ends of the plurality of microneedles respectively. The other end of the conductive leads extends out of the flexible substrate for electrical connection with a detection device and an electrical pulse generating device.

[0012] In one exemplary embodiment of this application, in the microneedle array, at least some of the microneedles among the plurality of microneedles in a first direction have different heights, and in a second direction, at least some of the microneedles among the plurality of microneedles have different heights; or

[0013] In the second direction, the height of the multiple microneedles gradually changes.

[0014] In one exemplary embodiment of this application, the lead ports of a plurality of conductive leads converge into three buses, which are respectively connected to three electrodes of an electrical pulse generator to control the electrodes of the corresponding microneedles to change between the anode and cathode.

[0015] In one exemplary embodiment of this application, the lead ports of the conductive leads of the same row of microneedles converge on the same bus, and the conductive leads of adjacent rows of microneedles converge on different buses.

[0016] In one exemplary embodiment of this application, the bus of the conductive lead connected to any one of the multiple microneedles is different from the bus of the conductive leads connected to the surrounding microneedles.

[0017] In one exemplary embodiment of this application, the needle body of the microneedle structure is provided with a barb structure for limiting the position of the flexible hollow electrical stimulation electrode array device within human tissue.

[0018] According to a second aspect of this application, a method for fabricating a flexible hollow electrical stimulation electrode array device is provided, comprising the following steps:

[0019] The surface layer of the substrate is processed, multiple through holes are processed on the flexible substrate, and multiple conductive leads are processed on the surface of the substrate, with each of the multiple conductive leads corresponding to a multiple of the through holes;

[0020] Microneedle array additive manufacturing involves using 3D printing technology to construct several microneedle electrode substrates of different heights from bottom to top by aligning the through holes on the upper surface of the substrate.

[0021] Microneedle array coating involves covering the upper surface of the substrate with a first mask. The unmasked portion of the first mask is the area where the microneedle electrode substrate is located. A conductive thin layer is deposited on the unmasked portion of the first mask using a vacuum coating process. After completion, the first mask is removed.

[0022] The insulating layer is deposited using a vacuum phase deposition process or a dip coating process to cover the entire insulating layer.

[0023] Reactive ion etching involves nesting a second mask on the upper surface of the substrate. The second mask exposes only the tip of the microneedle electrode substrate, masking all other surfaces. Liquid polyethylene glycol is filled between the second mask and the microneedle electrode substrate, and then solidified. The reactive ion etching process is used to remove the insulating layer from the exposed tip of the microneedle electrode substrate. After etching is complete, the second mask is removed, and the polyethylene glycol is liquefied and removed.

[0024] In one exemplary embodiment of this application, the following step is further included before depositing the insulating layer:

[0025] Electroplating involves placing the hollow electroporated microneedle array electrodes, which have undergone surface metallization, into the electroplating solution. All electrode leads are connected to the cathode of the power supply device, and the anode of the power supply device is connected to the plated metal electrode or inert electrode. A conductive layer of 2-10 μm is electroplated on the surface of the conductive thin film deposited by the coating process.

[0026] In one exemplary embodiment of this application, the following steps are also included:

[0027] A flexible substrate is fabricated, a master mold is 3D printed, a negative mold is obtained through a molding process, and a flexible substrate with a liquid reservoir is obtained through another molding process. The lower surface of the substrate substrate surface layer, which has been etched by reactive ion etching, is then attached to the flexible substrate to complete the fabrication of the electrostimulation electrode array device.

[0028] The exemplary embodiments of this application may have some or all of the following beneficial effects:

[0029] The flexible hollow electrostimulation electrode array device provided in the example embodiment of this application includes a flexible substrate and a microneedle array. A drug delivery channel is provided within the flexible substrate. The microneedle array is disposed on the flexible substrate and includes multiple microneedles, at least some of which have different heights to allow them to penetrate tissues to different depths. The lead ends of the microneedles are used for electrical connection to a detection device and an electrical pulse generator. Each microneedle has a hollow channel, with one end open at the tip of the microneedle and the other end open to connect to the drug delivery channel. When electroporation is required to allow large molecule drugs to enter the intracellular fluid, the flexible hollow electrostimulation electrode array device is implanted. Within human tissue, microneedles of varying heights penetrate to different depths. The lead end of the microneedle is first connected to a detection device, which detects the neurophysiological signals of the target brain region to determine the location and type of disease. After the detection is completed, the lead end of the microneedle is connected to an electrical pulse generator, which provides pulsed current to the microneedles at the corresponding depths to electroporate the tissue between the microneedles. This allows macromolecular drugs to enter the intracellular fluid through the nanopores of the cell membrane via electroporation, thereby treating the lesion. Furthermore, after a period of treatment, the lead end of the microneedle is reconnected to the detection device to monitor the treatment effect.

[0030] In addition, the flexible substrate has multiple independent conductive leads, which are electrically connected to the lead ends of multiple microneedles. Each microneedle is individually connected to an independent conductive lead. When the electrical pulse generator is connected through the lead ends, the polarity of each microneedle can be controlled, so that the polarities of adjacent microneedles are as different as possible. This further slows down the intensification of water electrolysis and the accumulation of hydroxide ions, and avoids the excessively high pH value around the cathode, which could cause cell death.

[0031] It should be understood that the above general description and the following detailed description are exemplary and explanatory only, and do not limit this application. Attached Figure Description

[0032] The accompanying drawings, which are incorporated in and form part of this specification, illustrate embodiments consistent with this application and, together with the description, serve to explain the principles of this application. It is obvious that the drawings described below are merely some embodiments of this application, and those skilled in the art can obtain other drawings based on these drawings without any inventive effort.

[0033] Figure 1 This paper shows a schematic diagram of the structure of a flexible hollow electrostimulation electrode array device according to Embodiment 1 of this application;

[0034] Figure 2 A side view of the flexible hollow electrostimulation electrode array device in Embodiment 1 of this application is shown;

[0035] Figure 3 This shows a schematic diagram of the conductive lead arrangement of the flexible substrate in Embodiment 1 of this application;

[0036] Figure 4 A schematic diagram of the back structure of the flexible substrate in Embodiment 1 of this application is shown;

[0037] Figure 5 A schematic diagram of the tip structure of the microneedle in Embodiment 1 of this application is shown;

[0038] Figure 6 This paper shows a schematic diagram of the structure of the flexible substrate connected to the infusion tube in Embodiment 1 of this application;

[0039] Figure 7 A schematic diagram of the convergence structure of the conductive leads in Embodiment 1 of this application is shown;

[0040] Figure 8 A schematic diagram of the upper surface of the substrate layer processed in Embodiment 2 of this application is shown;

[0041] Figure 9 A schematic diagram of the lower surface of the substrate layer processed in Embodiment 2 of this application is shown;

[0042] Figure 10 This paper shows a schematic diagram of the structure of the microneedle substrate produced by additive manufacturing in Embodiment 2 of this application;

[0043] Figure 11 This shows a schematic diagram of the structure covering the first mask plate in Embodiment 2 of this application;

[0044] Figure 12 A schematic diagram of the structure of the deposited insulating layer in Embodiment 2 of this application is shown;

[0045] Figure 13 A schematic diagram of the reactive ion etching structure in Embodiment 2 of this application is shown;

[0046] Figure 14 A side view of reactive ion etching in Embodiment 2 of this application is shown;

[0047] Figure 15 This shows a schematic diagram of the first angle structure of the flexible substrate processed by the molding process in Embodiment 2 of this application;

[0048] Figure 16 This paper shows a schematic diagram of the second angle structure of the flexible substrate processed by the molding process in Embodiment 2 of this application.

[0049] Explanation of reference numerals in the attached figures:

[0050] 001, First mask; 002, Second mask; 11, Flexible substrate; 111, Through-hole; 112, Conductive lead; 113, Lead port; 12, Microneedle array; 121, Electrode substrate; 122, Electrode conductive layer; 123, Electrode insulating layer; 13, Hollow channel; 14, Liquid reservoir; 15, Drug delivery port; 21, Conductive silver paste; 22, Signal line; 31, Infusion tube. Detailed Implementation

[0051] Exemplary embodiments will now be described more fully with reference to the accompanying drawings. However, these exemplary embodiments can be implemented in many forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this application will be thorough and complete, and will fully convey the concept of the exemplary embodiments to those skilled in the art. The same reference numerals in the drawings denote the same or similar structures, and therefore their detailed descriptions will be omitted. Furthermore, the drawings are merely illustrative of this application and are not necessarily drawn to scale.

[0052] Although relative terms such as "upper" and "lower" are used in this specification to describe the relative relationship of one component of an icon to another, these terms are used only for convenience, such as according to the orientation of the examples in the accompanying drawings. It is understood that if the device of the icon is flipped so that it is upside down, the component described as "upper" will become the component described as "lower." When a structure is "upper" of another structure, it may mean that the structure is integrally formed on the other structure, or that the structure is "directly" mounted on the other structure, or that the structure is "indirectly" mounted on the other structure through another structure.

[0053] The terms “a,” “one,” “the,” and “at least one” are used to indicate the existence of one or more elements / components / etc.; the terms “including” and “having” are used to indicate an open-ended inclusion and to mean that there may be other elements / components / etc. in addition to the listed elements / components / etc.; the terms “first” and “second” are used only as markers and are not a limitation on the number of objects. Example 1

[0054] This embodiment provides a specific implementation of a flexible hollow electrical stimulation electrode array device, such as... Figure 1 and Figure 2As shown, the device includes a flexible substrate 11 and a microneedle array 12. The microneedle array 12 is disposed on the flexible substrate 11 and includes multiple microneedles. At least some of the microneedles have different heights, which allows the microneedles to penetrate into tissues at different depths. The lead ends of the microneedles are used for electrical connection with a detection device and an electrical pulse generator. A drug delivery channel is provided in the flexible substrate 11. The microneedles have hollow channels 13. One end of the hollow channel 13 is open at the tip of the microneedle, and the other end is open to connect to the drug delivery channel. When electroporation is needed to open the cell membrane and generate a transient nanopore 111, a flexible hollow electrostimulation electrode array device is implanted into human tissue. The microneedles in the microneedle array 12 penetrate the tissue to different depths. The lead end of the microneedle is first connected to a detection device, which detects the neurophysiological signals at different depths to determine the location and type of disease in the target brain region. After the detection is completed, the lead end of the microneedle is then connected to an electrical pulse generator, which provides pulsed current to the microneedle, which can momentarily open the cell membrane and generate a transient nanopore 111. At this time, macromolecular drugs can enter the intracellular fluid through the nanopore 111. During the electroporation process, the hollow channel 13 of the microneedle is connected to the external drug through the drug delivery channel. The drug enters the hollow channel 13 through the drug delivery channel and enters the tip of the microneedle. When the transient nanopore 111 is generated by electroporation, the drug enters the intracellular fluid. After a period of treatment, the lead end of the microneedle can be reconnected to the detection device to detect the treatment effect.

[0055] In related technologies, the cerebral cortex is not a flat two-dimensional surface, but is composed of complex sulci and gyri (for example, the depth of the sulci in the human brain is 1-2 cm, and the width of the gyri is 2-3 cm). This complex anatomical structure means that existing microelectrode arrays may not be able to cover the target cortical area, which limits their coverage and accuracy in capturing neural signals. When performing electroporation, for some neurological diseases, it is usually necessary to detect the disease first and then perform electroporation. During the detection process, due to the unique structure of the cerebral cortex, the length of the detection needle may be insufficient or too long, requiring multiple needle replacements to detect the location of the lesion. There is even a possibility that the detection needle may be too long or too short, leading to deviations in detection. The technical solution of this application provides a microneedle array device for electroporation with microneedles of different heights. The height of the microneedles can be flexibly adjusted according to the depth of the target area. After the microneedles of different heights are inserted into human tissue, their tips can penetrate to different depths in the tissue. During the detection process, the condition at different depths in the tissue can be detected, thereby mitigating the negative impact that may be caused by the length of the detection needle. At the same time, the lead ends of the microneedles are connected to the detection device and the electrical pulse generation device respectively. The detection is carried out first and then the electrical pulse generation device is turned on. In this way, during the electroporation process, there is no need to replace the implanted microneedles, and the detection and electroporation operations can be completed simultaneously, saving operation steps and reducing damage to human tissue.

[0056] In this embodiment, as Figure 3 and Figure 4 As shown, multiple independent conductive leads 112 are provided on the flexible substrate 11. The multiple conductive leads 112 are electrically connected to the lead ends of multiple microneedles respectively. The other end of the conductive leads 112 extends from the flexible substrate 11 and is used to electrically connect with the detection equipment and the electrical pulse generating equipment. The microneedles can be electrically connected to the external detection equipment and electrical pulse generating equipment through the conductive leads 112.

[0057] In this embodiment, as Figure 6 As shown, in the microneedle array 12, multiple microneedles in the first direction have the same height, while in the second direction, at least some of the microneedles have different heights. Specifically, the heights of two adjacent microneedles may be different, or the heights of spaced-apart microneedles may be different. In other embodiments, the heights of the microneedles may be staggered, as long as there are microneedles of different heights to detect the corresponding tissue depth.

[0058] In other embodiments, the height of the microneedles in the second direction can vary gradually. Of course, regardless of whether it is the first or second direction, the overall microneedle array 12 can be irregular. The first and second directions can be horizontal and vertical, or they can be two directions at a certain angle, without specific limitations.

[0059] In related technologies, electroporation electrodes are all single-phase or biphase electrical pulses, which can lead to intensified water electrolysis and accumulation of hydroxide ions. The high pH value around the cathode can cause cell death. To solve this problem, in this embodiment, the lead ports 113 of several conductive leads 112 are combined into three buses. The three buses are connected to the three electrodes of the electrical pulse generator, which are used to control the corresponding microneedle electrodes to change between the anode and cathode, so that the tip of the electrode can electroporate the surrounding tissue, using a three-phase electrical pulse. When applying electrical stimulation, the several lead ports 113 are combined into three buses. The time interval is set according to the requirements, and one bus is alternately set as the anode and the other two buses are set as the cathode. The three buses are connected to the positive and negative terminals of the electrical pulse generator to apply stimulation pulse voltage. On the other hand, when performing nerve signal detection, each wire of the lead port 113 is connected to the detection device as a channel.

[0060] Furthermore, the lead ports of the conductive leads 112 of the same row of microneedles converge on the same bus, and the conductive leads 112 of adjacent rows of microneedles converge on different buses. This design allows the microneedles of adjacent rows to be the anode and cathode, respectively. For example, the three adjacent rows are the first row, the second row, and the third row, with the first and third rows being the cathodes and the second row being the anode, which enhances the effect of electroporation and can slow down water electrolysis and the accumulation of hydroxide ions.

[0061] Specifically, the bus line of the conductive lead 112 connected to any one of the microneedles is different from the bus line of the conductive lead 112 connected to the surrounding microneedles. This ensures that not only are the polarities of microneedles in different rows different, but also the polarities of two adjacent microneedles in the same row are different. This further slows down the intensification of water electrolysis and the accumulation of hydroxide ions, preventing the pH value around the cathode from becoming too high and causing cell death. Specifically, as... Figure 4 As shown, the position corresponding to through-hole 111 is used to construct microneedles. To illustrate this more clearly, [the following text is missing]. Figure 4 For example, I, II, and III correspond to three buses, each of which is electrically connected to the three electrodes of the electrical pulse generator. The electrical pulse generator can individually control the change of each bus between the anode and cathode. By continuously changing the polarity of the microneedles, the phenomenon of intensified water electrolysis and the accumulation of hydroxide ions can be further mitigated.

[0062] In this embodiment, the flexible substrate 11 can better fit the brain's tissue structure. Since the cerebral cortex has a certain curvature, the flexible substrate 11 can be adjusted according to the curvature of the cerebral cortex, and can better fit the cerebral cortex.

[0063] In this embodiment, the needle body of the microneedle structure is provided with a barb structure for limiting the position of the flexible hollow electrical stimulation electrode array device in human tissue.

[0064] Specifically, the microneedle body includes an upper cone and a lower frustum. The diameter of the bottom of the upper cone is larger than the top surface of the lower frustum. The portion of the bottom surface of the upper cone that is larger than the top surface of the lower frustum forms a barb structure. After being inserted into human tissue, the portion of the bottom surface of the upper cone that extends beyond the top surface of the lower frustum will block the microneedle from moving outward, thereby limiting the position of the microneedle array 12 device.

[0065] In other embodiments, the barb structure can also be a hook or claw extending from the side of the microneedle body, as long as it can prevent the microneedle from moving outward.

[0066] In this embodiment, as Figure 5 As shown, the tip of the microneedle includes an electrode substrate 121, an electrode conductive layer 122, and an electrode insulating layer 123. The electrode conductive layer 122 completely covers the surface of the electrode substrate 121 and is connected to conductive leads 112 on the surface of the flexible substrate 11. To accurately achieve local nerve signal acquisition while reducing unnecessary damage to skin and other tissues caused by stimulation voltage conducted through the conductive interface, and to improve the biosafety and accuracy of the stimulation area of ​​the hollow electroporation microneedle array electrode, a conformal insulating layer design is adopted on the electrode surface. The electrode insulating layer 123 exposes a region of several micrometers to tens of micrometers at the microneedle tip, and the size of the exposed area at the microneedle tip is adjusted according to the actual acquisition and stimulation range and the acquisition and stimulation effect. Specifically, the conductive layer of the microneedle electrode is made of a conductive material with high conductivity, high biocompatibility, and stable electrochemical performance, including but not limited to gold and platinum. The electrode insulating layer 123 is made of a highly biocompatible insulating material, including but not limited to parylene, polyimide, polyurethane, and polytetrafluoroethylene.

[0067] In this embodiment, as Figure 7 As shown, the lead port 113 of the microneedle array electrode is connected to the signal line 22 via conductive silver paste 21. When the function of acquiring neural electrical signals is realized, the other end of the signal line 22 is connected to an external interface or device; when the function of electrical stimulation is realized, the signal lines 22 are combined into three buses, and the other end is connected to a three-phase power supply that applies the electroporation stimulation voltage. The drug delivery port 15 on the bottom surface of the hollow electroporation microneedle array electrode is connected to the infusion tube 31. In other embodiments, the conductive silver paste 21 can be replaced with conductive adhesives such as solder or conductive paste; the signal line 22 can be conductive leads such as DuPont wire or metal wire; and the infusion tube 31 can be replaced with other tubing that can be used for drug injection.

[0068] In this embodiment, the thickness of the flexible substrate 11 is preferably 5 μm-25 μm, characterized by its ability to conform to the tissue structure of the experimental brain. Its length and width are determined by the number of microneedles and the arrangement of the electrode interconnection structure, preferably 3 mm-10 mm. The preferred dimensions of the microneedle array 12 are: height 100 μm-2 mm, bottom diameter 30-300 μm, tip diameter less than 10 μm, and center-to-center distance between adjacent microneedles preferably 200-2000 μm. The size of the hollow channel 13 is limited by the size of the microneedle array 12, and the sidewall thickness between the hollow channel and the microneedles is preferably 20-400 μm. The size of the liquid reservoir 14 is set according to the overall size of the substrate 11 and the microneedle array 12, characterized by being smaller than the overall size of the substrate 11 and larger than the overall size of the microneedle array 12. The size of the drug delivery port 15 depends on the size of the subsequent drug injection tubing.

[0069] Example 2

[0070] This embodiment provides a specific implementation of a method for fabricating a flexible hollow electrical stimulation electrode array device. The method for fabricating the flexible hollow electrical stimulation electrode array device in Embodiment 1 includes the following steps:

[0071] The surface layer of the substrate is processed, and multiple through holes 111 are processed on the flexible substrate, and multiple conductive leads 112 are processed on the surface of the substrate, with the multiple conductive leads 112 corresponding to the multiple through holes 111 respectively.

[0072] Furthermore, such as Figure 8 and Figure 9 As shown, during the processing of conductive leads 112, photolithography, development, and coating processes can be used, and through holes 111 can be processed by mechanical drilling, laser drilling, and etching processes. Specifically, the material of the substrate surface layer includes, but is not limited to, flexible materials such as polyimide and polyethylene terephthalate.

[0073] Microneedle array 12 additive manufacturing, such as Figure 10 As shown, several microneedle electrode substrates 121 of different heights are constructed from bottom to top through alignment holes 111 on the upper surface of the substrate using 3D printing technology.

[0074] Microneedle array 12 coating, such as Figure 11 As shown, a first mask is placed on the upper surface of the substrate. The part of the first mask that is not covered is the area where the microneedle electrode substrate 121 is located. A conductive thin layer is deposited on the part of the first mask that is not covered by a vacuum deposition process. After completion, the first mask is removed.

[0075] Deposited insulating layer, such as Figure 12 As shown, the entire structure is covered with an insulating layer using either vacuum phase deposition or dip coating processes.

[0076] Reactive ion etching, such as Figure 13 and Figure 14 As shown, a second mask 002 is nested on the upper surface of the substrate. The second mask 002 exposes only a localized tip of the microneedle electrode substrate 121, while masking all other surfaces. Liquid polyethylene glycol is filled between the second mask 002 and the microneedle electrode substrate 121. After filling, the polyethylene glycol is cured. A reactive ion etching process is used to remove the insulating layer from the exposed tip of the microneedle electrode substrate 121. After etching is completed, the second mask 002 is removed, and the polyethylene glycol is liquefied and removed.

[0077] Furthermore, the second mask plate 002 is a sleeve, which is sleeved on the outside of the microneedle electrode substrate 121. The height of the sleeve is slightly lower than the height of the microneedle electrode substrate 121. For example, if the height of the microneedle electrode substrate 121 is 50-100μm higher than the sleeve, liquid polyethylene glycol is filled into the sleeve and then solidified, so that only the tip of the microneedle electrode substrate 121 is exposed, which facilitates etching. At the same time, it can avoid etching other parts of the microneedle electrode substrate 121 during the etching process. Specifically, since the microneedle electrode substrates 121 in the microneedle array 12 provided in this application have different heights, during the windowing process (i.e., etching the tip of the microneedle electrode substrate to expose the internal conductive part), it is necessary to expose microneedle tips of the same height. Traditional masks are usually plates covering the tip of the microneedle electrode substrate. They are placed on the tip of the microneedle electrode substrate 121 before the deposition of the insulating layer. The depth to which the tip penetrates is the exposed height. Through the shielding of the mask, the conductive layer is exposed without the deposition of the insulating layer at the tip. However, such masks are obviously not suitable for the microneedle electrode substrates of different heights in this application. Therefore, this application adopts a unique sleeve structure, using 3D printing to print a sleeve of a preset height on the outer circumference of each microneedle electrode substrate 121. This allows for the printing of sleeves of different heights according to the different heights of the microneedle electrode substrate 121. This method greatly reduces the design difficulty of the mask, can adapt to the etching of microneedle electrode substrates 121 of different heights, ensures that the parts of the microneedle electrode substrate 121 that do not need to be etched are blocked, ensures the uniformity of the window opening, can improve the equality during signal array analysis, and avoids signal aliasing or large spatial positioning errors caused by the size difference of the microneedle electrode substrate 121.

[0078] In this embodiment, before depositing the insulating layer, an electroplating step is also included. The electroplating process involves placing the hollow electroporated microneedle array 12 electrodes, which have completed surface metallization, into the electroplating solution, and connecting all electrode leads to the cathode of the power supply device. The anode of the power supply device is connected to the plated metal electrode or inert electrode, and a 2-10 μm conductive layer is deposited on the surface of the conductive thin film deposited by the coating process.

[0079] In this embodiment, the step of processing the flexible substrate 11 is also included, such as... Figure 15 and Figure 16 As shown, a 3D printed master mold is used to obtain a negative mold through a molding process. Then, a flexible substrate 11 with a liquid reservoir 14 is obtained through a molding process. The lower surface of the substrate substrate layer that has been etched by reactive ion etching is attached to the flexible substrate 11 to complete the fabrication of the entire electrostimulation electrode array device.

[0080] Other embodiments of this application will readily conceive of by those skilled in the art upon consideration of the specification and practice of the embodiments thereof. This application is intended to cover any variations, uses, or adaptations of this application that follow the general principles of this application and include common knowledge or customary techniques in the art not claimed in this application. The specification and embodiments are to be considered exemplary only, and the true scope and spirit of this application are indicated by the appended claims.

Claims

1. A method for fabricating a flexible hollow electrical stimulation electrode array device, characterized in that, Includes the following steps: The surface layer of the substrate is processed, multiple through holes are processed on the flexible substrate, and multiple conductive leads are processed on the surface of the substrate, with each of the multiple conductive leads corresponding to a multiple of the through holes; Microneedle array additive manufacturing involves using 3D printing technology to construct several microneedle electrode substrates of different heights from bottom to top by aligning the through holes on the upper surface of the substrate. Microneedle array coating involves covering the upper surface of the substrate with a first mask. The unmasked portion of the first mask is the area where the microneedle electrode substrate is located. A conductive thin layer is deposited on the unmasked portion of the first mask using a vacuum coating process. After completion, the first mask is removed. The insulating layer is deposited using a vacuum phase deposition process or a dip coating process to cover the entire insulating layer. Reactive ion etching involves nesting a second mask on the upper surface of the substrate. The second mask exposes only the tip of the microneedle electrode substrate, while masking all other surfaces. Liquid polyethylene glycol is filled between the second mask and the microneedle electrode substrate. After filling, the polyethylene glycol is cured. The reactive ion etching process is then used to remove the insulating layer from the exposed tip of the microneedle electrode substrate. After etching is completed, the second mask is removed, and the polyethylene glycol is liquefied and removed. The second mask is a sleeve, which is fitted on the outside of the microneedle electrode substrate. The height of the sleeve is lower than the height of the microneedle electrode substrate, while the height of the microneedle electrode substrate is 50-100 μm higher than the sleeve. After filling the sleeve with liquid polyethylene glycol, the liquid polyethylene glycol is then solidified, so that only the tip of the microneedle electrode substrate is exposed, so as to etch the tip of the microneedle.

2. The preparation method according to claim 1, characterized in that, Before depositing the insulating layer, the following steps are also included: Electroplating involves placing the hollow electroporated microneedle array electrodes, which have undergone surface metallization, into the electroplating solution. All electrode leads are connected to the cathode of the power supply device, and the anode of the power supply device is connected to the plated metal electrode or inert electrode. A conductive layer of 2-10 μm is electroplated on the surface of the conductive thin film deposited by the coating process.

3. The preparation method according to claim 2, characterized in that, It also includes the following steps: A flexible substrate is fabricated, a master mold is 3D printed, a negative mold is obtained through a molding process, and a flexible substrate with a liquid reservoir is obtained through another molding process. The lower surface of the substrate substrate surface layer, which has been etched by reactive ion etching, is then attached to the flexible substrate to complete the fabrication of the electrostimulation electrode array device.

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