A flexible microneedle electrode and its preparation method

Abstract

This application relates to a flexible microneedle electrode and a preparation method thereof. The method includes: providing a prefabricated structure obtained by 3D printing, the prefabricated structure including a support plate and a plurality of microneedles arranged on the support plate; transferring the plurality of microneedles on the support plate to a first flexible material layer to obtain a microneedle array arranged on the first flexible material layer; forming a conductive layer, the conductive layer being arranged on the first flexible material layer and the microneedles of the microneedle array; forming a packaging layer, the packaging layer being arranged on the conductive layer to wrap the microneedles of the microneedle array and expose a part of the conductive layer located on the microneedles. Since a prefabricated structure with microneedles is first obtained by 3D printing and then the microneedles are transferred onto the flexible material layer to form a microneedle array, the flexibility of the microneedle electrode is ensured, the process is simple and the cost is reduced.

Description

Technical Field

[0001] This application relates to the field of microfabrication technology for flexible electronic devices, and particularly to a flexible microneedle electrode and a preparation method thereof. Background Art

[0002] Microneedles generally refer to needle-like structures with micron-scale dimensions fabricated through microfabrication processes, and the materials can be silicon, polymers, metals, etc. Microneedle electrodes for the body surface do not need to be implanted into the body or the nervous system through complex surgical procedures. They can extract bioelectric signals such as electroencephalogram (EEG), electrocardiogram (ECG), and electromyogram (EMG) just by attaching to the skin surface. This not only has a simple operation but also has no side effects. At the same time, microneedle electrodes have the characteristics of small size and good biocompatibility, and can be applied to narrow spaces that cannot be reached by traditional medical devices, providing better freedom for patients and causing less medical trauma to users. In addition, the microneedles have high dimensional accuracy and can accurately control the depth of penetration into the skin, and can be applied to precision medical instruments. Therefore, microneedle electrodes are of great significance for the research and development in the fields of life science and medicine.

[0003] However, rigid microneedle electrodes cannot fit well with the skin surface, which greatly interferes with the signal acquisition work and the accuracy of signals. Currently, there is relatively little research on flexible microneedle electrodes, and there are still problems such as complex processes and high costs. Summary of the Invention

[0004] In view of the above technical problems, this application provides a flexible microneedle electrode and a preparation method thereof. First, a prefabricated structure with microneedles is obtained by 3D printing, and then the microneedles are transferred onto a flexible material layer to form a microneedle array, ensuring the flexibility of the microneedle electrode, with a simple process and reduced costs.

[0005] To solve the above technical problems, this application provides a preparation method for a flexible microneedle electrode, including the following steps:

[0006] S1. Provide a prefabricated structure obtained by 3D printing, where the prefabricated structure includes a support plate and a plurality of microneedles arranged on the support plate;

[0007] S2. Transfer the plurality of microneedles on the support plate to a first flexible material layer to obtain a microneedle array arranged on the first flexible material layer;

[0008] S3. Form a conductive layer, where the conductive layer is arranged on the first flexible material layer and the microneedles of the microneedle array;

[0009] S4. Form a packaging layer, where the packaging layer is arranged on the conductive layer to wrap the microneedles of the microneedle array and expose a part of the conductive layer located on the microneedles.

[0010] Optionally, the step S1 includes:

[0011] Perform 3D printing using photosensitive resin to obtain the support plate and a plurality of microneedles disposed on the support plate;

[0012] Perform light irradiation curing on the support plate and the plurality of microneedles disposed on the support plate to obtain the prefabricated structure.

[0013] Optionally, the microneedles are arranged in an array on the support plate that is consistent with the microneedle array, and the step S2 includes:

[0014] Form a second flexible material layer on the side of the support plate where the microneedles are provided to wrap the microneedles;

[0015] Remove the support plate;

[0016] Transfer the microneedles wrapped by the second flexible material layer to the first flexible material layer to obtain a microneedle array disposed on the first flexible material layer.

[0017] Optionally, the step of removing the support plate includes:

[0018] Form a whole-surface protective layer on the second flexible material layer;

[0019] Use reactive ion etching to remove the support plate to obtain the microneedles wrapped by the second flexible material layer.

[0020] Optionally, a hollow structure is provided in the area of the support plate connected to the microneedles, and the step S2 includes:

[0021] Apply an external force to the microneedles on the prefabricated structure to break the hollow structure so that the microneedles are separated from the support plate;

[0022] Fix the separated microneedles on the first flexible material layer according to the arrangement of the microneedle array to obtain a microneedle array disposed on the first flexible material layer.

[0023] Optionally, a marker array is provided on the first flexible material layer, and the arrangement of the markers in the marker array is consistent with the arrangement of the microneedles in the microneedle array. The step of fixing the separated microneedles on the first flexible material layer according to the arrangement of the microneedle array to obtain a microneedle array disposed on the first flexible material layer includes:

[0024] Fix the separated microneedles at the positions of the markers in the marker array respectively to obtain a microneedle array disposed on the first flexible material layer.

[0025] Optionally, the step S2 further includes: first forming a preliminarily cured adhesive layer on the first flexible material layer, transferring a plurality of microneedles on the support plate to the preliminarily cured adhesive layer, and then curing the preliminarily cured adhesive layer.

[0026] Optionally, the step S3 includes:

[0027] Forming a photoresist layer on the surface of the microneedle array;

[0028] Patterning the photoresist layer;

[0029] Forming a metal layer on the photoresist layer;

[0030] Removing the photoresist layer and the part of the metal layer covering the photoresist layer to obtain the patterned conductive layer.

[0031] Optionally, the step S4 includes:

[0032] Forming a third flexible material layer on the conductive layer, and the third flexible material layer wraps the microneedles of the microneedle array;

[0033] Forming a patterned protective layer on the third flexible material layer, and the patterned protective layer exposes the target area corresponding to the microneedles on the third flexible material layer;

[0034] Using reactive ion etching to remove a part of the third flexible material layer corresponding to the target area to form the encapsulation layer.

[0035] The present application also provides a flexible microneedle electrode, which is prepared by using the preparation method of the flexible microneedle electrode described in any one of the above.

[0036] The flexible microneedle electrode and its preparation method of the present application, the method includes: providing a prefabricated structure obtained by 3D printing, the prefabricated structure includes a support plate and a plurality of microneedles arranged on the support plate; transferring the plurality of microneedles on the support plate to the first flexible material layer to obtain a microneedle array arranged on the first flexible material layer; forming a conductive layer, the conductive layer is arranged on the first flexible material layer and the microneedles of the microneedle array; forming an encapsulation layer, the encapsulation layer is arranged on the conductive layer to wrap the microneedles of the microneedle array and expose a part of the conductive layer located at the microneedles. Since a prefabricated structure with microneedles is first obtained by 3D printing and then the microneedles are transferred to the flexible material layer to form a microneedle array, the flexibility of the microneedle electrode is ensured, the process is simple and the cost is reduced. Description of the Drawings

[0037] Figure 1 is a schematic flowchart of a preparation method of a flexible microneedle electrode shown according to an embodiment;

[0038] Figure 2 It is a schematic diagram of a prefabricated structure used in the preparation method of a flexible microneedle electrode shown according to an embodiment;

[0039] Figures 3a - 3f It is a process schematic diagram of the preparation method of a flexible microneedle electrode shown according to an embodiment;

[0040] Figure 4 It is a schematic diagram of another prefabricated structure used in the preparation method of a flexible microneedle electrode shown according to an embodiment;

[0041] Figure 5 It is Figure 4 A top view schematic diagram of a microneedle at a prefabricated structure shown;

[0042] Figure 6 It is Figure 4 A partial cross-sectional schematic diagram of the prefabricated structure shown;

[0043] Figures 7a - 7f It is another process schematic diagram of the preparation method of a flexible microneedle electrode shown according to an embodiment. Specific embodiments

[0044] The following specific embodiments illustrate the implementation manners of the present application. Those skilled in the art can easily understand other advantages and effects of the present application from the content disclosed in this specification.

[0045] In the following description, reference is made to the accompanying drawings, which describe several embodiments of the present application. It should be understood that other embodiments may also be used, and mechanical composition, structure, electrical, and operational changes may be made without departing from the spirit and scope of the present application. The following detailed description should not be considered restrictive. The terms used herein are only for describing specific embodiments and are not intended to limit the present application.

[0046] Although in some instances the terms first, second, etc. are used herein to describe various elements, these elements should not be limited by these terms. These terms are only used to distinguish one element from another.

[0047] Furthermore, as used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, unless the context clearly dictates otherwise. It should be further understood that the terms "comprises" and / or "comprising", when used in this specification, specify the presence of stated features, steps, operations, elements, components, items, kinds, and / or groups, but do not preclude the presence, occurrence, or addition of one or more other features, steps, operations, elements, components, items, kinds, and / or groups. The terms "or" and "and / or" as used herein are to be construed as inclusive or meaning any one or any combination. Thus, "A, B or C" or "A, B and / or C" means "any of the following: A; B; C; A and B; A and C; B and C; A, B and C". Exceptions to this definition occur only when the combination of elements, functions, steps or operations are inherently mutually exclusive in some manner.

[0048] Figure 1 is a schematic flow chart of a method for preparing a flexible microneedle electrode according to an embodiment. As Figure 1 shown, the method for preparing a flexible microneedle electrode of the present application includes the following steps:

[0049] S1. Provide a prefabricated structure obtained by 3D printing, the prefabricated structure including a support plate and a plurality of microneedles disposed on the support plate;

[0050] Among them, the materials and processes of 3D printing can be selected according to the required hardness, size, dimensional accuracy, etc. of the microneedles. In this embodiment, a photosensitive resin is preferably used for 3D printing, and the prefabricated structure is obtained by curing under ultraviolet light or other light beams, and microneedles with a smooth surface and high precision can be obtained. The process is simple and the preparation cost is reduced. Optionally, step S1 includes:

[0051] Perform 3D printing using a photosensitive resin to obtain a support plate and a plurality of microneedles disposed on the support plate;

[0052] Perform light irradiation curing on the support plate and the plurality of microneedles disposed on the support plate to obtain a prefabricated structure.

[0053] Among them, the support plate is integrally connected to multiple microneedles and is used to stably support the microneedles before transfer. In one embodiment, the microneedles include a first part and a second part that are integrally connected. The first part has a tip, which can facilitate the penetration of the microneedles into the skin. The second part is a pedestal-shaped support structure located at the bottom of the first part, which can provide bottom support for the microneedles after the microneedles are transferred to a flexible substrate, so that the microneedles can be designed to be of a greater height and avoid collapse. When the height of the microneedles increases, the depth of the microneedles inserted into the skin becomes deeper, enabling the electrodes to penetrate through the dermis layer to be closer to the signal source, thereby greatly improving the quality of the collected bioelectric signals. In actual implementation, the multiple microneedles are arranged on the support plate in a regular or irregular shape, and the microneedles can have the same or different shapes among them.

[0054] S2. Transfer the multiple microneedles on the support plate to the first flexible material layer to obtain a microneedle array disposed on the first flexible material layer;

[0055] Among them, the first flexible material layer has flexibility, which can enable the device to better conform to the skin surface and reduce the influence of human movement on the circuit and signal acquisition. The material of the first flexible material layer can be at least one of PI (polyimide), Parylene (poly-p-xylene), and PDMS (polydimethylsiloxane). In this embodiment, PI with better flexibility is preferably used. The thickness of the first flexible material layer is 5 - 15 μm. If the thickness is too thin, it is not sufficient to support the microneedles; if the thickness is too thick, it will limit the flexibility of the device.

[0056] In one embodiment, the microneedles are arranged on the support plate in an array consistent with the microneedle array. The step S2 includes:

[0057] Form a second flexible material layer on the side of the support plate provided with the microneedles to wrap the microneedles;

[0058] Remove the support plate;

[0059] Transfer the microneedles wrapped by the second flexible material layer to the first flexible material layer to obtain a microneedle array disposed on the first flexible material layer.

[0060] Among them, the second flexible material layer uses Parylene. Parylene has good conformal properties, can firmly wrap the microneedles, and plays a role in conformal and support, ensuring the position accuracy during the transfer process. Optionally, the step of removing the support plate includes:

[0061] Form a whole-surface protective layer on the second flexible material layer;

[0062] Remove the support plate by reactive ion etching to obtain the microneedles wrapped by the second flexible material layer.

[0063] Among them, magnetron sputtering or deposition can be used to coat the surface of the second flexible material layer with metallic copper as a protective layer, which plays a role in protecting Parylene during reactive ion etching and facilitating observation. After removing the support plate by reactive ion etching, microneedles wrapped by the second flexible material layer can be obtained. Transferring the microneedles wrapped by the second flexible material layer to the first flexible material layer can directly obtain a microneedle array disposed on the first flexible material layer.

[0064] In another embodiment, a hollow structure is provided in the region of the support plate connected to the microneedles. Step S2 includes:

[0065] Applying an external force to the microneedles on the prefabricated structure to break the hollow structure so that the microneedles are separated from the support plate;

[0066] Fixing the separated microneedles on the first flexible material layer according to the arrangement of the microneedle array to obtain a microneedle array disposed on the first flexible material layer.

[0067] Among them, a hollow structure is provided in the region of the support plate connected to the microneedles. Under the action of a relatively small external force, the microneedles can be removed from the support plate, avoiding or reducing damage to the microneedles. When using a hollow structure, multiple microneedles can be arranged on the support plate in regular or irregular shapes. During transfer, they are fixed on the first flexible material layer according to the arrangement of the microneedle array to obtain a microneedle array.

[0068] Optionally, to improve the position accuracy during transfer, a mark array can be pre-formed on the first flexible material layer. The arrangement of the marks in the mark array is consistent with the arrangement of the microneedles in the microneedle array. Then, the step of fixing the separated microneedles on the first flexible material layer according to the arrangement of the microneedle array to obtain a microneedle array disposed on the first flexible material layer specifically includes: respectively fixing the separated microneedles at the marks in the mark array to obtain a microneedle array disposed on the first flexible material layer. Among them, the mark array can adopt a patterned metal layer. For example, a layer of metallic copper is sputtered on the first flexible material layer, and then the metallic copper layer is patterned by photolithography etching to define an array pattern to mark the arrangement position of the microneedles on the first flexible material layer.

[0069] Optionally, step S2 further includes: first forming a preliminarily cured adhesive layer on the first flexible material layer, transferring the multiple microneedles on the support plate to the preliminarily cured adhesive layer, and then curing the preliminarily cured adhesive layer.

[0070] Among them, first, a sacrificial layer and a first flexible material layer are sequentially spin-coated on a clean rigid substrate and cured by gradient thermal baking. The sacrificial layer can be made of polymethyl methacrylate (PMMA). Then, if the microneedles are transferred by the aforementioned method of directly removing the support plate, a preliminarily cured adhesive layer is formed on the first flexible material layer. For example, a material of the first flexible material layer with a lower concentration suitable for transfer is spin-coated on the surface of the first flexible material layer and preliminarily cured by short-time low-temperature baking to form an adhesive layer. Then, the microneedles wrapped by the second flexible material layer are transferred onto the incompletely cured adhesive layer. Finally, the adhesive layer is cured to fix the microneedles on the first flexible material layer. Or, if the microneedles are transferred by the aforementioned method of setting a hollow structure to separate the microneedles from the support plate, first, the aforementioned mark array is formed on the first flexible material layer, and then a preliminarily cured adhesive layer is formed on the first flexible material layer. For example, a material of the first flexible material layer with a lower concentration suitable for transfer is spin-coated on the surface of the first flexible material layer and preliminarily cured by short-time low-temperature baking to form an adhesive layer. Then, under a microscope, the microneedles are removed from the support plate with sharp tweezers and placed at the marked positions on the first flexible material layer. Finally, the adhesive layer is cured to fix the microneedles on the first flexible material layer.

[0071] S3. Form a conductive layer, which is disposed on the first flexible material layer and the microneedles of the microneedle array;

[0072] Among them, the material of the conductive layer is a metal with good conductivity such as CrAu or TiAu, preferably CrAu. The Cr layer is located below the Au layer. The conductivity of Au is good and can transmit various nerve signals and electrical signals. The thickness of Au is sufficient to meet the conductivity requirements and will not fall off. Optionally, the conductive layer includes a wire part for connecting the microneedles and the circuit interface. The wire part is wavy, which can increase the ductility of the device and will not damage the circuit when the device fits the skin surface. Optionally, the microneedle array includes microneedle units arranged in a matrix. The microneedle unit includes at least one microneedle. The wire part includes a plurality of laterally extending wires and a plurality of longitudinally extending wires. The microneedle unit is located at the intersection of the laterally extending wires and the longitudinally extending wires. Thus, compared with the case where all the microneedles in the traditional microneedle array belong to the same electrode, the circuit patterning process can also realize the functions of multiple discrete microneedle electrodes according to requirements, ensuring the quality and accuracy of the collected signals.

[0073] When forming the conductive layer, first form a photoresist layer on the surface of the microneedle array. After patterning the photoresist layer, form a metal layer on the photoresist layer. Remove the photoresist layer and the part of the metal layer covering the photoresist layer, and then the patterned conductive layer can be obtained. In one implementation, first form a first photoresist layer, perform a full-surface exposure on the first photoresist layer, and then form a second photoresist layer on the first photoresist layer. The first photoresist layer and the second photoresist layer can be formed by spraying to make the photoresist evenly distributed, so as to avoid the less photoresist at the tip of the microneedle affecting the pattern accuracy of the conductive layer. Then, use laser direct writing to perform patterned exposure on the second photoresist layer. Using this non-contact exposure technology of laser direct writing for high-step patterning of the photoresist can improve the pattern accuracy and avoid damaging the microneedles caused by traditional contact exposure. After that, develop the first photoresist layer and the second photoresist layer to expose the areas of the microneedles and the first flexible material layer where the conductive layer needs to be formed. Then, use the magnetron sputtering process to form a metal layer. Finally, soak the device in acetone to remove the first photoresist layer, the second photoresist layer, and the metal layer covering the second photoresist layer, and form a patterned conductive layer.

[0074] S4. Form an encapsulation layer. The encapsulation layer is disposed on the conductive layer to wrap the microneedles of the microneedle array and expose a part of the conductive layer located at the microneedles.

[0075] Among them, the encapsulation layer is disposed on the conductive layer to wrap the microneedles and expose the part of the conductive layer located at the microneedles, that is, the part of the conductive layer at the position of the microneedles is not blocked by the encapsulation layer to realize the function of the microneedles as electrodes. Preferably, the part of the conductive layer located at the tips of the microneedles is exposed to better protect and support the microneedles. In actual implementation, the encapsulation layer also exposes the part of the conductive layer located at the circuit interface, for example, exposes the position of the pad. The encapsulation layer uses Parylene. Parylene has good conformal properties, can firmly coat the microneedles, play a role in conformal and support, and has good tensile properties, and can fit well with the skin surface.

[0076] When forming the encapsulation layer, first form a third flexible material layer on the conductive layer. The third flexible material layer wraps the microneedles of the microneedle array. Then, form a patterned protective layer on the third flexible material layer. The patterned protective layer exposes the corresponding target area of the third flexible material layer where the microneedles are located. Then, use reactive ion etching to remove the part of the third flexible material layer corresponding to the target area to form the encapsulation layer. Specifically, first deposit a whole surface of Parylene on the microneedle array using a vapor deposition process, sputter a layer of copper on the surface of the Parylene as a protective layer, then spin-coat a layer of photoresist on it, and perform an exposure process on the photoresist through a laser direct writing device. The exposed part is the part of the microneedles. After that, develop and remove the photoresist located on the microneedles, use a copper etching solution to remove the copper located on the microneedle part, exposing the Parylene located on the microneedles, while the other parts of the Parylene are blocked by copper. Then, place the device in a Rie etching machine and etch the exposed Parylene with oxygen, finally exposing the part of the conductive layer located on the microneedles to transmit electrical signals. After that, use a copper etching solution to remove the copper located on the other parts of the microneedles.

[0077] Through the above steps, first use 3D printing to obtain a prefabricated structure with microneedles, and then transfer the microneedles to a flexible material layer to form a microneedle array, which not only ensures the flexibility of the microneedle electrodes, but also makes the process simpler and reduces the cost.

[0078] The following details two specific preparation processes of the present application.

[0079] The first preparation process:

[0080] Figure 2 is a schematic diagram of a prefabricated structure used in a preparation method of a flexible microneedle electrode shown according to an embodiment. As Figure 2As shown, the prefabricated structure is obtained by 3D printing, including a support plate 51 and a plurality of microneedles 5 arranged on the support plate 51. The microneedles 5 are arranged in an array on the support plate 51 that is consistent with the microneedle array. The support plate 51 and the plurality of microneedles 5 are integrally connected to stably support the microneedles 5 before transfer. The microneedles 5 include a first part and a second part that are integrally connected. The first part has a tip to facilitate the insertion of the microneedles 5 into the skin. The second part is a pedestal-shaped support structure at the bottom of the first part, which can provide bottom support for the microneedles 5 after the microneedles 5 are transferred to a flexible substrate. Thus, the microneedles 5 can be designed to be of a greater height and can avoid collapse. When the height of the microneedles 5 increases, the depth of insertion of the microneedles 5 into the skin is deeper, enabling the electrodes to penetrate through the dermis layer to be closer to the signal source, thereby greatly improving the quality of the collected bioelectric signals. Among them, the materials and processes of 3D printing can be selected according to requirements such as the required hardness, size, and dimensional accuracy of the microneedles 5. In this embodiment, a photosensitive resin is preferably used for 3D printing, and the prefabricated structure is obtained by curing through ultraviolet light or other light beams irradiation, and smooth-surface and high-precision microneedles 5 can be obtained. The process is simple and the preparation cost is reduced.

[0081] Use Figure 2 A preparation process for preparing a flexible microneedle electrode using the prefabricated structure shown is as Figures 3a - 3f shown. Please refer to Figure 3a , after obtaining the prefabricated structure by 3D printing, first form a second flexible material layer 71 on the side of the support plate 51 where the microneedles 5 are provided to wrap the microneedles 5. Then, deposit a layer of metallic copper 81 on the surface of the second flexible material layer 71 by magnetron sputtering or deposition as a protective layer 81. The metallic copper 81 does not serve as a conductive layer but plays a role in protecting the second flexible material layer 71 during reactive ion etching and facilitating observation.

[0082] Please refer to Figure 3b , remove the support plate 51 by reactive ion etching to obtain the microneedles 5 wrapped by the second flexible material layer 71, and then place the microneedles 5 wrapped by the second flexible material layer 71 in a copper etching solution to etch and remove the metallic copper 81 on the surface.

[0083] Please refer to Figure 3c , first spin-coat a sacrificial layer 2 and a first flexible material layer 3 on a clean rigid substrate 1 in sequence and cure them by gradient thermal baking. The rigid substrate 1 can be a silicon wafer, and the sacrificial layer 2 can be polymethyl methacrylate (PMMA). Then, form a preliminarily cured adhesive layer on the first flexible material layer 3 ( Figure 3c(not shown in the figure). For example, a material with a lower concentration suitable for transfer is spin-coated on the surface of the first flexible material layer 3 to form a sticking layer through preliminary curing by baking at a low temperature for a short time. Then, the microneedles 5 wrapped by the second flexible material layer 71 are transferred onto the not fully cured sticking layer. Finally, the sticking layer is cured to fix the microneedles 5 on the first flexible material layer 3, realizing the transfer of the microneedles 5 wrapped by the second flexible material layer 71 to the first flexible material layer 3, and obtaining a microneedle array disposed on the first flexible material layer 3.

[0084] Please refer to Figure 3d , a conductive layer 6 is formed. The conductive layer 6 is disposed on the first flexible material layer 3 and the microneedles 5 of the microneedle array. The preparation process of the conductive layer 6 refers to the description of the above-mentioned step S3 and will not be elaborated here. After forming the conductive layer 6, a third flexible material layer 72 such as Parylene is plated on the whole surface.

[0085] Please refer to Figure 3e , a patterned protective layer 82 is formed on the third flexible material layer 72. The patterned protective layer 82 exposes the target area of the third flexible material layer 72 corresponding to the position of the microneedles 5. Then, the corresponding part of the third flexible material layer 72 in the target area is removed by reactive ion etching to form a packaging layer. Specifically, when forming the patterned protective layer 82, a layer of metallic copper is sputtered on the surface of the third flexible material layer 72, and then a layer of photoresist 9 is spin-coated on it. The photoresist 9 is exposed by a laser direct writing device. The exposed part is the part of the microneedles 5. After that, the photoresist located on the microneedles 5 is developed and removed, and the metallic copper located on the part of the microneedles 5 is removed by a copper etching solution, thus obtaining the patterned protective layer 82, exposing the third flexible material layer 72 located on the microneedles 5, while the other parts of the third flexible material layer 72 are blocked.

[0086] Please refer to Figure 3f , the device is placed in a Rie etching machine, and the exposed third flexible material layer 72 is etched by reactive ion to form a packaging layer, exposing the parts of the conductive layer 6 located on the microneedles 5 and the circuit interface for transmitting electrical signals. Finally, the photoresist 9 and the patterned protective layer 82 are removed, and the device is taken off the rigid substrate 1 to complete the preparation of the flexible microneedle electrode.

[0087] The second preparation process:

[0088] Figure 4 is a schematic diagram of another prefabricated structure used in the preparation method of the flexible microneedle electrode shown according to an embodiment. As Figure 4 shown, the prefabricated structure is obtained by 3D printing, including a support plate 51 and a plurality of microneedles 5 disposed on the support plate 51. The microneedles 5 can be arranged in an array on the support plate 51 or arranged irregularly.

[0089] The material and process of 3D printing can be selected according to the requirements of the hardness, size, dimensional accuracy, etc. of the microneedles 5. In this embodiment, photosensitive resin is preferably used for 3D printing, and after being irradiated and cured by ultraviolet light or other light beams, a prefabricated structure can be obtained, and microneedles 5 with a smooth surface and high precision can be obtained. The process is simple and the preparation cost is reduced.

[0090] The support plate 51 is integrally connected to the multiple microneedles 5 and is used to stably support the microneedles 5 before transfer. The microneedles 5 include an integrally connected first part and second part. The first part has a tip, which can facilitate the microneedles 5 to pierce the skin. The second part is a frustum-shaped support structure located at the bottom of the first part, which can provide bottom support for the microneedles 5 after the microneedles 5 are transferred to the flexible substrate, so that the microneedles 5 can be allowed to be designed to be of a greater height and can avoid collapse. When the height of the microneedles 5 is increased, the depth of the microneedles 5 inserted into the skin is deeper, so that the electrode can penetrate through the dermis layer to be closer to the signal source, thereby greatly improving the quality of the collected bioelectric signals.

[0091] A hollow structure 52 is provided in the area of the support plate 51 connected to the microneedles 5, so that the microneedles 5 can be removed from the support plate 51 under a relatively small external force, avoiding or reducing damage to the microneedles 5. Please refer to Figure 5 , the hollow structure 52 includes a hollow area and connecting beams 521. The slender support structure formed by the connecting beams 521 can effectively reduce the external force required to separate the microneedles 5. In actual implementation, please also refer to Figure 6 , a groove 522 is provided at one end of the connecting beam 521 connected to the microneedles 5 to further reduce the cross-sectional area at the connection between the connecting beam 521 and the microneedles 5. A cavity 523 can also be provided below the hollow structure 52. Thus, when it is necessary to remove the microneedles 5 from the support plate 51, the hollow structure 52 can be damaged by simply pressing down slightly, and the operation is simple.

[0092] Use Figure 4 A preparation process for preparing a flexible microneedle electrode using the prefabricated structure shown is as Figures 7a - 7f shown. Please refer to Figure 7a , first, a sacrificial layer 2 and a first flexible material layer 3 are sequentially spin-coated on a clean rigid substrate 1 and cured by gradient heat baking. The sacrificial layer 2 can be made of polymethyl methacrylate (PMMA). Then, a marker array is formed on the first flexible material layer 3. The arrangement of the markers 4 in the marker array is the same as the arrangement of the microneedles 5 in the expected microneedle array. The marker array can be a patterned metal layer. For example, a layer of metallic copper is sputtered on the first flexible material layer 3, and then the metallic copper layer is patterned by photolithography etching to define an array pattern composed of the markers 4 to mark the arrangement positions of the microneedles 5 on the first flexible material layer 3. After that, a preliminarily cured adhesive layer is formed on the first flexible material layer 3 ( Figure 7a(not shown in the figure), for example, a material with a relatively low concentration suitable for transfer is spin-coated on the surface of the first flexible material layer 3, and preliminary curing is performed through short-time low-temperature baking to form an adhesive layer.

[0093] Please refer to Figure 7b , use Figure 4 For the prefabricated structure shown, metal copper can be pre-coated on the surface of the microneedles 5 by magnetron sputtering or deposition to facilitate observation during operation. Then, an external force is applied to the microneedles 5 on the prefabricated structure to break the hollow structure 52 so that the microneedles 5 are separated from the support plate 51. Specifically, under a microscope, the microneedles 5 can be removed from the support plate 51 with sharp tweezers. Next, the microneedles 5 removed from the support plate 51 are placed at the position of the mark 4 on the first flexible material layer 3, and then the adhesive layer is cured to fix the microneedles 5 on the first flexible material layer 3, realizing the fixation of the separated microneedles 5 on the first flexible material layer 3 according to the arrangement of the microneedle array, and obtaining a microneedle array provided on the first flexible material layer 3. After that, the device can be placed in a copper etching solution to remove the copper on the surface of the microneedles 5.

[0094] Please refer to Figure 7c , a conductive layer 6 is formed. The conductive layer 6 is provided on the first flexible material layer 3 and the microneedles 5 of the microneedle array. The preparation process of the conductive layer 6 refers to the description of the above S3 step and will not be elaborated here.

[0095] Please refer to Figure 7d , after forming the conductive layer 6, a third flexible material layer 7 such as Parylene is coated on the whole surface.

[0096] Please refer to Figure 7e , a patterned protective layer 8 is formed on the third flexible material layer 7. The patterned protective layer 8 exposes the target area of the third flexible material layer 7 corresponding to the microneedles 5, and then the corresponding part of the third flexible material layer 7 in the target area is removed by reactive ion etching to form a packaging layer. Specifically, when forming the patterned protective layer 8, a layer of metal copper is sputtered on the surface of the third flexible material layer 7, and then a layer of photoresist 9 is spin-coated on it. The photoresist 9 is exposed by a laser direct writing device. The exposed part is the part of the microneedles 5. After that, the photoresist 9 located on the microneedles 5 is developed and removed, and the metal copper located on the part of the microneedles 5 is removed with a copper etching solution, and then the patterned protective layer 8 can be obtained, exposing the third flexible material layer 7 located on the microneedles 5, while the other parts of the third flexible material layer 7 are blocked.

[0097] Please refer to Figure 7f, place the device into a RIE etcher, and use reactive ions to etch the exposed third flexible material layer 7 to form a packaging layer, exposing the portions of the conductive layer 6 located at the microneedles 5 and the circuit interface for transmitting electrical signals. Finally, remove the photoresist 9 and the patterned protective layer 8, and remove the device from the rigid substrate 1 to complete the preparation of the flexible microneedle electrode.

[0098] This application also provides a flexible microneedle electrode, which is prepared by using the preparation method of the flexible microneedle electrode described in any one of the above.

[0099] According to the preparation method of the present application, the distribution and shape of the microneedles on the flexible substrate can be designed according to requirements. At the same time, through 3D printing technology, complex microneedle shapes with more reasonable mechanical structures that are not available in other microneedle preparation methods can be realized, ensuring that the microneedles maintain their original shapes during repeated insertion and removal. In addition, 3D printing technology can achieve batch production of microneedles with simple processes; the flexible microneedle electrode prepared according to the preparation method of the present application can painlessly penetrate and adhere to the target surface to achieve long-term continuous in-situ real-time monitoring of the target; according to the preparation method of the present application, both of the two implementation processes can achieve the preparation of the flexible microneedle electrode and obtain good results. Among them, the second preparation process is more flexible than the first preparation process and is more suitable for experimental optimization of aspects such as the three-dimensional structure and distribution of microneedles in the early stage, while the first preparation process is more convenient than the second preparation process and has a greater prospect of mass production.

[0100] The above embodiments are only illustrative of the principles and effects of the present application and are not intended to limit the present application. Any person familiar with this technology can modify or change the above embodiments without departing from the spirit and scope of the present application. Therefore, all equivalent modifications or changes made by those with ordinary knowledge in the technical field without departing from the spirit and technical ideas disclosed in the present application should still be covered by the claims of the present application.

Claims

1. A preparation method of a flexible microneedle electrode, characterized in that, It includes the following steps: S1. Provide a prefabricated structure obtained by 3D printing, the prefabricated structure including a support plate and a plurality of microneedles arranged on the support plate; S2. Transfer the plurality of microneedles on the support plate to a first flexible material layer to obtain a microneedle array arranged on the first flexible material layer; S3. Form a conductive layer, the conductive layer being arranged on the first flexible material layer and on the microneedles of the microneedle array; S4. Form a packaging layer, the packaging layer being arranged on the conductive layer to wrap the microneedles of the microneedle array and exposing a part of the conductive layer located on the microneedles; Among them, step S2 includes: Form a second flexible material layer on the side of the support plate provided with microneedles to wrap the microneedles, the second flexible material layer being Parylene; Form a whole-surface protective layer on the second flexible material layer; Remove the support plate by reactive ion etching to obtain microneedles wrapped by the second flexible material layer; Transfer the microneedles wrapped by the second flexible material layer to the first flexible material layer to obtain a microneedle array arranged on the first flexible material layer.

2. The method according to claim 1, characterized in that The S1 step includes: Perform 3D printing using a photosensitive resin to obtain the support plate and a plurality of microneedles arranged on the support plate; Perform light irradiation curing on the support plate and the plurality of microneedles arranged on the support plate to obtain the prefabricated structure.

3. The method according to claim 1 or 2, characterized in that, A hollow structure is arranged in the area of the support plate connected to the microneedles. The S2 step includes: Apply an external force to the microneedles on the prefabricated structure to break the hollow structure so that the microneedles are separated from the support plate; Fix the separated microneedles on the first flexible material layer according to the arrangement of the microneedle array to obtain a microneedle array arranged on the first flexible material layer.

4. The method according to claim 3, characterized in that, A marking array is arranged on the first flexible material layer, and the arrangement of the marks in the marking array is consistent with the arrangement of the microneedles in the microneedle array. The step of fixing the separated microneedles on the first flexible material layer according to the arrangement of the microneedle array to obtain a microneedle array arranged on the first flexible material layer includes: Fix the separated microneedles at the corresponding marks in the marking array respectively to obtain a microneedle array arranged on the first flexible material layer.

5. The method according to claim 1, characterized in that The S2 step further includes: first form a preliminarily cured adhesive layer on the first flexible material layer, transfer the plurality of microneedles on the support plate to the preliminarily cured adhesive layer, and then cure the preliminarily cured adhesive layer.

6. The method according to claim 1, wherein The S3 step includes: Form a photoresist layer on the surface of the microneedle array; Pattern the photoresist layer; Form a metal layer on the photoresist layer; Remove the photoresist layer and the part of the metal layer covering the photoresist layer to obtain the patterned conductive layer.

7. The method according to claim 1, characterized in that, The S4 step includes: Form a third flexible material layer on the conductive layer, the third flexible material layer wrapping the microneedles of the microneedle array; A patterned protective layer is formed on the third flexible material layer, and the patterned protective layer exposes a target area of the third flexible material layer corresponding to the microneedles. A reactive ion etching is used to remove a part of the third flexible material layer corresponding to the target area to form the encapsulation layer.

8. A flexible microneedle electrode, characterized in that, It is prepared by using the preparation method of the flexible microneedle electrode according to any one of claims 1 to 7.

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