Soft 3D conical silica gel neural electrode tip exposure method

Abstract

The invention provides a method for exposing the tip of a soft 3D conical silica gel neural electrode. The method comprises the following steps: step 1, manufacturing a resin male die and a resin female die based on a photocuring 3D printer; secondly, patterning of a soft silica gel insulating layer at an electrode point is achieved through alignment pressing and covering between a resin male die and a resin female die; 3, transferring the cured soft silica gel insulating layer to an acrylic mold with a conical groove by using a water-soluble adhesive tape; and 4, blade-coating conductive silica gel to fill the conical groove of the acrylic mold, and spin-coating an insulating silica gel packaging layer. According to the invention, the insulating packaging layer and the internal conductive structure of the 3D neural electrode point are both based on the soft silica gel material, so that the same-matrix silica gel packaging of the 3D neural electrode point and the direct exposure of the electrode tip are realized; the problems that binding force is insufficient due to a heterogeneous material interface between an insulating layer and a conducting layer of an existing soft 3D neural electrode, and exposure patterning of the tip of the 3D electrode is difficult can be effectively solved.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomedical electronics, and particularly relates to a method for exposing the tip of a flexible 3D conical silicone nerve electrode. Background Art

[0002] Minimally invasive implantable brain-computer interface nerve electrodes are crucial for the treatment of neurological diseases. However, traditional flexible 2D planar nerve electrodes are difficult to conformally attach to the cerebral cortex, while rigid 3D piercing nerve electrodes are easily wrapped by glial cells, seriously affecting nerve signal acquisition and stimulation regulation. During signal acquisition, the amplitude of the recorded nerve signal will be significantly attenuated and the signal-to-noise ratio will decrease. During stimulation regulation, the stimulation voltage will increase exponentially to reach the threshold current, which is likely to cause tissue damage. Flexible 3D nerve electrodes effectively solve these two key problems. They not only achieve gapless direct contact between the nerve electrode and brain tissue without causing brain tissue damage, but also there are no glial cells on the electrode surface, enabling effective nerve signal acquisition and stimulation regulation.

[0003] However, how to expose only the tip region of the flexible 3D nerve electrode to accurately acquire and stimulate brain tissue and avoid the dissipation of electrical signals into the tissue fluid around the 3D electrode points is a key problem to be solved urgently. Traditional minimally invasive implantable nerve electrodes are mostly based on microelectromechanical system (MEMS) processes, involving key steps such as photolithography, etching, and transfer printing. This requires the material to be stable enough, not easily deformed, and have a relatively high etching rate. However, the Young's modulus of flexible silicone materials is low and they have high elasticity, and they are extremely susceptible to deformation during the photolithography process due to factors such as the centrifugal force during spin coating, the alignment pressure of the mask, and the thermal stress during heat treatment, seriously affecting the photolithography accuracy. Moreover, the low surface energy and surface chemical inertness on the surface of flexible silicone materials will lead to poor adhesion of photoresist, and it may fall off during the development process due to physical flushing or chemical corrosion, resulting in overdevelopment and further affecting the pattern size and accuracy. In addition, the etching rate of flexible silicone materials is very low, resulting in a significant increase in process complexity and cost. Finally, flexible silicone materials are prone to adsorbing and swelling in organic solvents (such as acetone), deforming or even degrading, affecting the accurate transfer of patterns. Therefore, traditional MEMS processes are only suitable for 2D planar patterning, and it is difficult to achieve 3D patterning with a high aspect ratio. The flexible silicone material exacerbates this problem, and how to accurately and controllably expose the tip of the flexible 3D nerve electrode has been facing a severe challenge.

[0004] Through the retrieval of the prior art, it was found that S.P. DeWeerth et al. from the Georgia Institute of Technology in the United States wrote the article "A stretchable microneedle electrode array for stimulating and measuring intramuscular electromyographic activity" in IEEE Transactions on Neural Systems and Rehabilitation Engineering, 2016, 25(9): 1440-1452, and developed a stretchable microneedle electrode array composed of a polydimethylsiloxane (PDMS) substrate, a stretchable wire formed by doping PDMS with gold powder, and a stainless steel needle electrode. The substrate, wire, and 3D hemispherical electrode points of this electrode are all made of soft materials, with good flexibility and stretchability. However, the tip of this electrode is exposed by piercing through the soft 3D hemispherical electrode point with a rigid stainless steel microneedle, and the problem of tip exposure of the soft 3D electrode point is not directly solved.

[0005] To avoid introducing rigid microneedles into the soft 3D electrode to achieve tip exposure of the electrode point, Flavia Vitale et al. from the University of Pennsylvania in the United States wrote the article "MXene-infused bioelectronic interfaces for multiscale electrophysiology and stimulation" in Science Translational Medicine, 2021, 13(612): eabf8629, and developed a class of soft, high-resolution, large-scale 3D bioelectronic interfaces realized by Ti 3 C 2 MXene (a two-dimensional transition metal carbide nanomaterial) and scalable solution processing. This electrode is based on rapid prototyping and customizing the array geometry through a laser patterning process, and the top encapsulation layer is cut with a biopsy punch to expose the 3D electrode contacts. However, this 3D electrode point exposure process lacks reliable and precise control over the exposed area, and only cylindrical soft 3D electrode points can be formed. Moreover, the insulating coating of the 3D electrode point is not homogeneous with the electrode conductive material and is prone to delamination and failure.

[0006] To fabricate a conical soft 3D electrode, Peng Shi et al. from City University of Hong Kong, China, published an article "Multifunctional hydrogel electronics for closed-loop antiepileptic treatment" in Science Advances, 2024, 10(47): eadq9207, reporting a hydrogel-based soft 3D conical nerve electrode. The hydrogel solution was filled into a PDMS mold with conical grooves and induced polymerization by ultraviolet irradiation to achieve a soft 3D hydrogel conical electrode point. However, this soft 3D conical electrode point is completely exposed without an insulating layer coating, making it impossible to achieve precise focusing of nerve signal acquisition and stimulation regulation.

[0007] Similarly, CN118163355A discloses a method for fabricating a soft 3D hydrogel microneedle electrode array. This method uses a silicon mold with conical grooves and a silica hard mask to inject a conductive hydrogel precursor solution, ultimately forming a conical soft 3D hydrogel electrode point. This fabrication process has simple steps, low cost, and is easy to scale up production. However, this soft 3D conical electrode point is also completely exposed without an insulating layer coating, only having the problem of the tip being exposed.

[0008] Through the analysis of the above existing technologies, it can be seen that the currently disclosed soft 3D conical silicone nerve electrodes have problems such as easy delamination and cracking of the insulating layer, difficulty in exposing the tip, and inability to precisely control the exposed area. Summary of the Invention

[0009] The purpose of the present invention is to solve the defects and blanks in the existing technologies, and provides a method for exposing the tip of a soft 3D conical silicone nerve electrode, which can effectively achieve the encapsulation of the soft silicone 3D nerve electrode point with the same matrix silicone and directly expose the electrode tip, effectively solving the problems that the current soft 3D nerve electrodes are prone to delamination and falling off due to the heterogeneous material interface between the insulating layer and the conductive layer, resulting in electrode failure, it is difficult to pattern soft silicone materials by traditional MEMS processes, and it is difficult to expose the tip of the soft 3D conical silicone nerve electrode.

[0010] To achieve the above purpose, the technical solution provided by the present invention is:

[0011] On the one hand, a method for exposing the tip of a soft 3D conical silicone nerve electrode is provided, including the following steps:

[0012] Step 1: Fabricate a resin male mold and a female mold based on a stereolithography 3D printer. The multiple protrusions of the male mold and the multiple grooves of the female mold are both of an isosceles trapezoidal cross-sectional structure. The top side lengths of the trapezoids of the protrusions and the corresponding grooves are equal. The height and the base angle of the trapezoid of the male mold are both larger than those of the trapezoid of the female mold, so as to form a structured void during alignment and pressing. The dimensions of each of the trapezoids of the male mold and the female mold are determined according to the pattern of the nerve electrode to be formed.

[0013] Step 2: Spin-coat insulating silicone on the surface of the resin female mold, and then align and press the resin male mold and the female mold.

[0014] Step 3: Cure the insulating silicone to obtain a 3D electrode point soft silicone insulating layer that has been patterned and formed, and then remove the resin male mold.

[0015] Step 4: Use a water-soluble tape to bond the surface of the soft silicone insulating layer on the resin female mold, transfer it to an acrylic mold with conical grooves inside, and then dissolve the water-soluble tape with water. Among them, the number and distribution of the conical grooves in the acrylic mold are the same as those of the trapezoidal resin female mold, but the height is greater. The conical angle determines the exposed shape of the tip of the 3D electrode point to be formed.

[0016] Step 5: Scrape and coat conductive silicone to fill the conical grooves of the acrylic mold, and dry and cure it to form a soft silicone conductive area inside the electrode point, thereby obtaining a formed 3D conical silicone electrode point.

[0017] Step 6: Spin-coat an insulating silicone encapsulation layer and dry and cure it, and demold to form an array of soft 3D conical silicone nerve electrode points with exposed tips.

[0018] Further, Step 4 can be replaced with the following steps:

[0019] Step 4.1: Spin-coat photoresist to fill the internal grooves of the cured soft silicone insulating layer.

[0020] Step 4.2: Irradiate ultraviolet light to cure the photoresist.

[0021] Step 4.3: Use a water-soluble tape to bond the surface of the cured photoresist, and transfer it and the soft silicone insulating layer together to an acrylic mold with conical grooves inside.

[0022] Step 4.4: Dissolve the water-soluble tape with water.

[0023] Step 4.5: Heat the dimethyl sulfoxide solution to dissolve the photoresist.

[0024] Further, in Step 1, the depth of the protrusions and the grooves is 50 - 1000 μm, and the base angle of the trapezoid is 10° - 170°.

[0025] Furthermore, the resin punch and die are made of one or more photocurable resin materials such as polyurethane acrylate, epoxy acrylate, epoxy resin, and composite photocurable resin.

[0026] Furthermore, in Steps 2 and 6, the insulating silica gel is made of one or more of polydimethylsiloxane, linear triblock copolymer, and Ecoflex / Dragonskin series platinum-catalyzed silicone rubber.

[0027] Furthermore, in Step 4, the acrylic mold with conical grooves is fabricated by numerical control milling and polished to make its surface smooth.

[0028] Furthermore, in Step 5, the conductive silica gel is obtained by uniformly blending multi-walled carbon nanotube powder into the insulating silica gel material, with a doping mass ratio of 5% - 30% and the tube length of a single carbon nanotube being 2 - 50 μm.

[0029] Furthermore, the photoresist is selected from SU-8 photoresist or AZ photoresist.

[0030] On the other hand, a method for exposing the tip of a flexible 3D conical silica gel nerve electrode is also provided, including the following steps:

[0031] Step 1, fabricate a conical resin punch and die based on a photocurable 3D printer. The multiple protrusions of the punch and the multiple grooves of the die are both dome conical structures. The dome sizes of the protrusions and the corresponding grooves are the same. The height and bottom angle of the punch cone are both larger than those of the die cone to form a structured void during alignment and pressing, and the dimensions of the trapezoids of the punch and the die are determined according to the pattern of the nerve electrode to be formed;

[0032] Step 2, spray a release agent on the surface of the resin punch, spin-coat insulating silica gel on the surface of the resin die, and then align and press the resin punch and die;

[0033] Step 3, cure the insulating silica gel to obtain a 3D electrode point flexible silica gel insulating layer with a patterned shape, and then remove the resin punch;

[0034] Step 4, scrape and coat the conductive silica gel to fill the conical grooves of the resin die, and dry and cure it to form a flexible silica gel conductive area inside the electrode point, thereby obtaining a formed 3D conical silica gel electrode point;

[0035] Step 5, spin-coat an insulating silica gel encapsulation layer and dry and cure it to demold and form an array of tip-exposed flexible 3D conical silica gel nerve electrode points.

[0036] The advantages of the present invention are:

[0037] 1. In the present invention, both the insulating encapsulation layer and the internal conductive structure of the 3D neural electrode points are based on a soft silicone material, realizing the encapsulation of the 3D neural electrode points with the same matrix silicone and the direct exposure of the electrode tips.

[0038] 2. The present invention prepares a resin silicone mold based on a photocuring 3D printing mechanism, realizes the patterning of the soft silicone encapsulation layer through the direct alignment and pressing of the molds, and realizes the transfer through a water-soluble tape, capable of quickly, accurately, and controllably preparing a tip-exposed soft silicone 3D neural electrode without delamination and cracking failure phenomena.

[0039] 3. The present invention also uses a cured photoresist as a transfer support layer, capable of avoiding the alignment difficulties and low transfer accuracy caused by the extremely easy deformation of the soft ultra-thin silicone structure during the transfer process.

[0040] 4. The present invention also designs a tip-precise exposure process for a one-step forming soft silicone 3D neural electrode without transfer, effectively reducing the process difficulty and further improving the tip exposure accuracy of the soft silicone 3D neural electrode. BRIEF DESCRIPTION OF THE DRAWINGS

[0041] Through the following description with reference to the drawings, the above and / or other features and advantages of the present invention will become more readily understood. The drawings are not drawn to scale, and some features are enlarged or reduced to show the details of specific components. In the drawings:

[0042] Figure 1 is a schematic structural diagram of a soft 3D tapered silicone neural electrode array of the present invention;

[0043] Figure 2 is a schematic diagram of the pressure deformation of the tip-exposed soft 3D tapered silicone neural electrode of the present invention;

[0044] Figure 3 is a process flow diagram of the tip exposure process of the soft 3D tapered silicone neural electrode of the present invention;

[0045] Figure 4 is a schematic diagram of the optimized process of photoresist-assisted transfer of the present invention;

[0046] Figure 5 is a schematic diagram of the optimized process of direct forming without transfer of the present invention.

[0047] In the figure: 1 - tip exposure area; 2 - tip insulation area; 3 - soft substrate; 4 - pad exposure area; 5 - wire; 6 - pressure source; 7 - trapezoidal resin punch; 8 - trapezoidal resin die; 9 - conical acrylic die; 10 - conical resin punch; 11 - conical resin die. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0048] The present invention will be described in detail below with reference to the accompanying drawings by means of exemplary embodiments of the present invention. It should be noted that the following detailed description of the present invention is for illustrative purposes only and does not limit the present invention.

[0049] The present invention provides a method for exposing the tip of a soft 3D conical silicone nerve electrode, which has very important practical value and innovative significance for achieving precise nerve signal acquisition and stimulation. It can effectively solve the problems of the current soft 3D nerve electrode, such as the inhomogeneity between the insulating layer and the electrode material, the difficulty in tip exposure, and the lack of reliable and precise control of the exposed area, and provides support for the innovative process research of soft 3D nerve electrodes.

[0050] The overall structure of the soft 3D conical silicone nerve electrode array prepared according to the present invention is as Figure 1 shown. The electrode is entirely made of soft silicone material, including multiple soft electrode points. The soft electrode points are 3D conical structures, including a tip exposure area 1 based on conductive silicone and a tip insulation area 2 based on insulating silicone. The nerve electrode array also includes a soft substrate 3, a pad exposure area 4, and a wire 5, and has flexibility and stretchability. The tip of the soft electrode point is precisely exposed, and the soft silicone material endows the soft 3D electrode with the ability to withstand pressure deformation without failure, which is conducive to achieving precise focused nerve signal acquisition and stimulation and is suitable for long-term in vivo implantation.

[0051] The structural schematic of the tip-exposed soft 3D conical silicone nerve electrode prepared according to the present invention under pressure deformation is as Figure 2 shown. Different from traditional rigid 3D microneedle nerve electrodes, the 3D nerve electrode of the present invention is entirely based on silicone material, including a soft electrode tip and a soft substrate 3. The entire 3D nerve electrode has no metal material, and the entire electrode array has the same low Young's modulus characteristics as the silicone material, and can be stretched, bent, or elastically deformed without failure. It can not only conformally adhere to the cerebral cortex, but also adapt to the deformation of brain tissue caused by reasons such as changes in intracranial pressure. Under the action of an external pressure source 6, the soft 3D conical silicone nerve electrode of the present invention can withstand pressure deformation, and the tip exposure area 1 and the tip insulation area 2 of the electrode will not be stratified, cracked, or failed, and will not affect normal nerve signal acquisition and stimulation. The soft and stable 3D conical silicone nerve electrode is of great significance for long-term and effective in vivo implantation of nerve signal acquisition and stimulation.

[0052] Next, the method for exposing the tip of the soft 3D conical silicone nerve electrode provided by the present invention will be described in detail.

[0053] The method for exposing the tip of the soft 3D conical silicone nerve electrode according to an exemplary embodiment of the present invention includes the following steps:

[0054] Step S1, fabricate a resin male mold and a female mold based on a stereolithography 3D printer. The multiple protrusions of the male mold and the multiple grooves of the female mold are both of an isosceles trapezoid cross-sectional structure. The top side lengths of the trapezoids of the protrusions and the corresponding grooves are equal. The height and the base angle of the trapezoid of the male mold are both larger than those of the trapezoid of the female mold, so as to form a structured void when aligned and pressed. The respective dimensions of the trapezoids of the male mold and the female mold are determined according to the pattern of the neural electrode points to be formed.

[0055] Step S2, spin-coat insulating silicone on the surface of the resin female mold, and then align and press the resin male mold and the female mold.

[0056] Step S3, cure the insulating silicone to obtain a 3D electrode point soft silicone insulating layer that has been patterned and formed, and then remove the resin male mold.

[0057] Step S4, use a water-soluble tape to bond the surface of the soft silicone insulating layer on the resin female mold, transfer it to an acrylic mold with conical grooves inside, and then dissolve the water-soluble tape with water. Among them, the number and distribution of the conical grooves in the acrylic mold are the same as those of the trapezoidal resin female mold, but the height is greater. The cone angle determines the exposed shape of the tip of the 3D electrode point to be formed.

[0058] Step S5, scrape and coat conductive silicone to fill the conical grooves of the acrylic mold, and dry and cure it to form a soft silicone conductive area inside the electrode point, thereby obtaining a formed 3D conical silicone electrode point.

[0059] Step S6, spin-coat an insulating silicone encapsulation layer and dry and cure it, and demold to obtain a soft 3D conical silicone neural electrode point array with exposed tips.

[0060] According to the present invention, the depth of the protrusions and the grooves is 50 - 1000 μm, and the base angle of the trapezoid is 10° - 80°.

[0061] The resin male mold and the female mold are optionally made of one or more photocurable resin materials such as polyurethane acrylate, epoxy acrylate, epoxy resin, and composite photocurable resin.

[0062] In Steps 2 and 6, the insulating silicone can be made of one or more of polydimethylsiloxane (PDMS), linear triblock copolymer (SEBS), and platinum-catalyzed silicone rubbers of the Ecoflex / Dragonskin series.

[0063] In Step S4, the shape of the conical groove is generally a round-top cone to form an arc-shaped exposed area of the 3D electrode point. When the arc surface can better adhere to the cerebral cortex, it will not cause damage to the brain tissue.

[0064] Refer to Figure 3 This embodiment can be implemented through the following steps:

[0065] Step (1): Fabricate a trapezoidal resin male mold 7 and a trapezoidal resin female mold 8 based on a stereolithography 3D printer. The protrusions and grooves are of an isosceles trapezoidal structure with different base angles. The height of the isosceles trapezoid of the male mold is 200 microns, and the height of the isosceles trapezoid of the female mold is 100 microns. The top side lengths of the male mold and the isosceles trapezoid of the male mold are both 100 microns, but the bottom side length of the isosceles trapezoid of the male mold is 150 microns, and the bottom side length of the isosceles trapezoid of the female mold is 200 microns. The base angle of the isosceles trapezoid of the male mold is approximately 60 degrees, and the base angle of the isosceles trapezoid of the female mold is approximately 55 degrees. Therefore, when aligning and pressing, the upper surface of the trapezoidal structure will be tightly pressed and aligned, while a structured gap will appear in the side wall area of the trapezoidal structure. The gap size is 1 - 30 microns (1 micron at the narrowest part and 30 microns at the thickest part), which is used for patterning and filling insulating silicone in Step 2 to form the electrode tip insulation region 2.

[0066] Step (2): Spray a silicone release agent (silicone oil-based release agent or polytetrafluoroethylene (PTFE)-type release agent) on the surface of the trapezoidal resin male mold 7, and spray 3 - 5 times to ensure that a layer of release agent adheres to the surface of the trapezoidal resin male mold 7.

[0067] Step (3): Spin-coat insulating silicone on the surface of the trapezoidal resin female mold 8 at a speed of 750 revolutions per minute, and the thickness of the obtained silicone is 200 microns to ensure that the insulating silicone completely fills the trapezoidal groove of the female mold.

[0068] Step (4): Align and press the trapezoidal resin male mold 7 and the trapezoidal resin female mold 8 so that the upper surfaces of the male and female molds of the trapezoidal structure are tightly pressed without gaps to prevent the uncured liquid insulating silicone from seeping in.

[0069] Step (5): Place the trapezoidal resin male mold 7 and the trapezoidal resin female mold 8 that are aligned and pressed in an oven at a temperature of 100 °C for 60 minutes to completely cure the insulating silicone.

[0070] Step (6): Slowly remove the trapezoidal resin male mold 7 to obtain the patterned and formed insulating silicone electrode tip insulation region 3, whose shape and size are determined by the dimensions of the trapezoidal resin male mold 7 and the trapezoidal resin female mold 8 in Step (1) (including the height of the isosceles trapezoid, the top side, the bottom side dimensions, and the base angle).

[0071] Step (7): Bond the surface of the cured insulating silicone in Step (5) with a water-soluble tape to demold the patterned and formed insulating silicone electrode tip insulation region 3 from the surface of the trapezoidal resin female mold 8 for the next transfer. The thickness of the water-soluble tape is 200 microns and it can be completely dissolved in deionized water.

[0072] Step (8): Precisely transfer the electrode tip insulation region 3 to the conical acrylic female mold 9 with a conical groove inside. The number, distribution, and bottom angle of the conical grooves are the same as those of the trapezoidal resin female mold 8, but the height is greater, which is 150 microns. The conical acrylic female mold 9 is fabricated by high-precision CNC milling and polished to make its surface smooth.

[0073] Step (9): Immerse the water-soluble tape in ionized water to completely dissolve it. It takes 20 minutes for the water-soluble tape to completely dissolve in water.

[0074] Step (10): Scrape and coat the conductive silicone to fill the conical grooves of the conical acrylic female mold 9, and place it in an oven for drying and curing at a temperature of 100 °C for 60 minutes. The conductive silicone is obtained by uniformly blending multi-walled carbon nanotube powder with a tube length of 30 microns into the insulating silicone, and the doping mass ratio is 5% - 30%, especially 15%. The tube length of a single carbon nanotube is 2 - 50 μm. After actual measurement, for the conductive silicone with a doping ratio of 15%, the sheet resistance can be as low as 5 Ω / Square. A doping ratio greater than 30% will cause the Young's modulus of the conductive silicone to increase, which is not conducive to the overall softness of the 3D nerve electrode. While a doping ratio lower than 5% will result in non-conductivity because the percolation threshold cannot be reached.

[0075] Step (11): Spin-coat the insulating silicone and dry and cure it. The spin-coating speed is 750 revolutions per minute, the oven temperature is 100 °C, and the time is 60 minutes. The obtained silicone soft substrate 4 has a thickness of 200 μm.

[0076] Step (12): Demold the encapsulated and formed finished electrode from the surface of the conical acrylic female mold 9 to obtain a soft 3D conical silicone nerve electrode dot array.

[0077] In this embodiment, during the transfer process of step S4, since the thickness of the patterned and formed insulating silicone electrode tip insulation region 3 is extremely small (1 - 30 microns), the electrode tip insulation region 3 is extremely prone to deformation, surface adhesion, etc. during the transfer process, resulting in a significant decrease in transfer accuracy and even transfer failure. To solve this problem, this embodiment proposes a photoresist-assisted transfer method to improve the transfer accuracy and thus improve the tip exposure accuracy of the soft silicone 3D nerve electrode.

[0078] Specifically, step S4 can be replaced with the following steps:

[0079] Step S4.1, Spin-coat the photoresist to fill the internal grooves of the cured soft silicone insulating layer;

[0080] Step S4.2, Irradiate ultraviolet light to cure the photoresist;

[0081] Step S4.3: Bond the surface of the cured photoresist with a water-soluble tape, and transfer it together with the flexible silicone insulating layer to an acrylic mold with a conical groove inside.

[0082] Step S4.4: Dissolve the water-soluble tape with water.

[0083] Step S4.5: Heat the dimethyl sulfoxide solution to dissolve the photoresist.

[0084] Preferably, the photoresist can be selected from SU-8 photoresist or AZ photoresist.

[0085] Refer to Figure 4 , the optimized process of photoresist-assisted transfer proposed in this embodiment can be realized through the following steps:

[0086] Step (1): After the trapezoidal resin punch 7 and the trapezoidal resin die 8 are aligned and pressed to form the patterned electrode tip insulation region 2 and the punch is demolded, spin-coat the SU-8 photoresist. Initially at a low speed of 500 rpm for 10 seconds, then maintain a low-medium speed of 800 rpm for 60 seconds to evenly spread the SU-8 photoresist. Then, irradiate ultraviolet light to cure the SU-8 photoresist, with the ultraviolet light intensity of 20 mW / cm 2 , and the exposure time of 100 seconds. Finally, perform post-exposure baking at a temperature of 95 °C for 10 minutes to complete the cross-linking reaction of the SU-8 photoresist.

[0087] Step (2): Bond the surface of the cured SU-8 photoresist with a 200-micron-thick water-soluble tape for the next transfer step.

[0088] Step (3): Demold the electrode tip insulation region 3 from the surface of the photocuring resin 3 die and transfer it to the conical acrylic die 9.

[0089] It should be noted that the electrode tip insulation region 3 is a 1-30-micron-thick flexible silicone (1 micron at the narrowest part and 30 microns at the thickest part), which is extremely easy to deform or adhere to the surface during the transfer process, resulting in transfer failure. The cured SU-8 photoresist can provide a supporting role during the transfer process, which is beneficial to ensuring that the electrode tip insulation region 3 maintains its original shape and achieving accurate transfer.

[0090] Step (4): Immerse the water-soluble tape in water, and after 20 minutes, the water-soluble tape is completely dissolved.

[0091] Step (5): Heat the dimethyl sulfoxide (DMSO) solution to 80 °C and completely immerse the cured SU-8 photoresist. Keep the DMSO temperature at 80 °C and immerse for 6 hours to completely dissolve the SU-8 photoresist.

[0092] It should be noted that organic solvents such as acetone are difficult to dissolve the fully cross-linked and cured SU-8 photoresist, but can easily dissolve the conical acrylic female mold 9. However, the heated DMSO solution can slowly dissolve the SU-8 photoresist 4, but has a very weak dissolving ability for the conical acrylic female mold 9. Therefore, choosing the heated DMSO solution as the solvent can completely remove the SU-8 photoresist support structure while hardly affecting the conical acrylic female mold 9, facilitating the formation of the conductive silicone in the last step.

[0093] Step (6): Scraping and coating the conductive silicone to fill the conical groove of the conical acrylic female mold 9, and placing it in an oven for drying and curing at a temperature of 100 °C for 60 minutes to obtain the formed 3D conical silicone electrode point. The subsequent encapsulation and release steps are the same as those in the above embodiment.

[0094] Therefore, as described above, in this embodiment, both the insulating encapsulation layer and the internal conductive structure of the 3D nerve electrode point are based on the soft silicone material, realizing the homogeneous matrix silicone encapsulation of the 3D nerve electrode point and the direct exposure of the electrode tip. In addition, this embodiment is based on the photocuring 3D printing mechanism to prepare the resin silicone mold, realizes the patterning of the soft silicone encapsulation layer through the direct alignment and pressing of the molds, and realizes the transfer through the water-soluble tape, and can quickly, accurately, and controllably prepare the tip-exposed soft silicone 3D nerve electrode without delamination and cracking failure phenomena.

[0095] According to the present invention, in order to further improve the tip exposure accuracy of the soft silicone 3D nerve electrode, a high-precision dedicated photocuring 3D printer can be used to directly print the conical resin female mold with a domed conical groove, realizing the direct forming optimization process of the tip exposure of the soft 3D silicone electrode point without transfer. The reason is that only when the resolution is high enough can the domed conical structure be printed. In the above embodiment, a general photocuring 3D printer with a low resolution can only print a flat-top trapezoidal structure. Although the high-resolution photocuring 3D printer has a higher equipment cost, it will greatly reduce the process cost and complexity and improve the process accuracy.

[0096] In this regard, the method for tip exposure of the soft 3D conical silicone nerve electrode according to another exemplary embodiment of the present invention includes the following steps:

[0097] Step S1, making a conical resin male mold and a female mold based on a photocuring 3D printer. The multiple protrusions of the male mold and the multiple grooves of the female mold are both domed conical structures. The domed sizes of the protrusions and the corresponding grooves are the same. The height and the bottom angle of the cone of the male mold are both larger than those of the female mold to form a structured void during alignment and pressing. The respective sizes of the trapezoid of the male mold and the trapezoid of the female mold are determined according to the pattern of the nerve electrode to be formed;

[0098] Step S2: Spray a release agent on the surface of the resin male mold, spin-coat an insulating silica gel on the surface of the resin female mold, and then align and press the resin male mold and the female mold together.

[0099] Step S3: Cure the insulating silica gel to obtain a patterned and formed 3D electrode point soft silica gel insulating layer, and then remove the resin male mold.

[0100] Step S4: Scrape and coat a conductive silica gel to fill the conical grooves of the resin female mold, and dry and cure it to form a soft silica gel conductive area inside the electrode point, thereby obtaining a formed 3D conical silica gel electrode point.

[0101] Step S5: Spin-coat an insulating silica gel encapsulation layer and dry and cure it to demold and form a soft 3D conical silica gel nerve electrode point array with exposed tips.

[0102] Refer to Figure 5 , this embodiment can be realized through the following steps:

[0103] Step (1): Fabricate a conical resin male mold 10 and a conical resin female mold 11 based on a photocuring 3D printer. At this time, the protrusion and groove structures are optimized from the trapezoid in the above embodiment to a dome cone shape, thus avoiding the subsequent transfer step. Therefore, there is no need to worry about the deformation problem of the insulating area 3 at the electrode tip during the transfer process and the alignment problem during the transfer process. The protrusion height is 200 microns, and the depression depth is 150 microns. The bottom angle of the dome cone of the protrusion is 70 degrees, and the bottom angle of the dome cone of the depression is 50 degrees. Then, spray a release agent on the surface of the conical resin male mold 10 and spin-coat an insulating silica gel on the surface of the conical resin female mold 11.

[0104] Step (2): Align and press the conical resin male mold 10 and the conical resin female mold 11 together. The dome areas will be tightly pressed and aligned, and structured voids will appear in the sidewall areas for patterned filling of the insulating silica gel. The void size is 1 - 20 microns (1 micron at the narrowest part and 20 microns at the thickest part). Then, dry it in an oven to cure the insulating silica gel, at a temperature of 100 °C for 60 minutes.

[0105] Step (3): Slowly remove the conical resin male mold 10 to obtain the patterned and formed insulating area 3 at the electrode tip.

[0106] Step (4): At this time, the conical resin female mold 11 can replace the conical acrylic female mold 9 in the above embodiment. Therefore, without the transfer step, directly scrape and coat a conductive silica gel to fill the conical grooves of the conical resin female mold 11, and place it in an oven to dry and cure it, at a temperature of 100 °C for 60 minutes, to obtain a formed 3D conical silica gel electrode point.

[0107] Step (5): Spin-coat insulating silicone and dry and cure it. The spin-coating speed is 1000 revolutions per minute, the oven temperature is 100 °C, and the time is 60 minutes. The obtained soft substrate 4 has a thickness of 150 μm.

[0108] Step (6): Demold the formed finished electrode from the surface of the conical resin die 11 to obtain a soft 3D conical silicone nerve electrode point array.

[0109] Therefore, as described above, in this embodiment, both the insulating encapsulation layer and the internal conductive structure of the 3D nerve electrode points are based on soft silicone materials, realizing the homogenous matrix silicone encapsulation of the 3D nerve electrode points and the direct exposure of the electrode tips. In addition, the one-step forming process of the soft silicone 3D nerve electrode with accurate tip exposure without transfer effectively reduces the process difficulty and further improves the tip exposure accuracy of the soft silicone 3D nerve electrode.

[0110] Finally, it should be noted that the features mentioned and / or shown in the above description of the exemplary embodiments of the present invention can be combined in the same or similar manner into one or more other embodiments, combined with the features in other embodiments or replace the corresponding features in other embodiments. The technical solutions obtained through such combination or replacement should also be regarded as being included within the protection scope of the present invention.

Claims

1. A method for exposing the tip of a soft 3D conical silicone nerve electrode, characterized in that: The following steps are involved: Step 1, making a resin male mold and a female mold based on a light-curing 3D printer, wherein the multiple protrusions of the male mold and the multiple grooves of the female mold are all isosceles trapezoidal cross-sectional structures, the top side lengths of the protrusions and the corresponding trapezoids of the grooves are equal, the height and bottom angle of the male mold trapezoid are larger than those of the female mold trapezoid, so as to form a structured gap during alignment and lamination, and the dimensions of the male mold trapezoid and the female mold trapezoid are determined according to the pattern of the neural electrode to be formed; Step 2, spin-coating insulating silicone on the surface of the resin concave mold, and then aligning the resin convex mold and the concave mold for pressing; Step 3, solidifying the insulating silicone to obtain a patterned 3D electrode point soft silicone insulating layer, and then removing the resin convex mold; Step 4, use water-soluble tape to bond the surface of the soft silicone insulation layer on the resin concave mold, transfer it to the acrylic mold with conical grooves inside, and then dissolve the water-soluble tape with water, wherein the number and distribution of the conical grooves in the acrylic mold are consistent with those of the trapezoidal resin concave mold, but the height is larger, and the cone angle determines the exposed shape of the tip of the 3D electrode point to be formed; Step 5, apply conductive silicone to fill the conical groove of the acrylic mold, and dry and solidify it to form a soft silicone conductive area inside the electrode point, thereby obtaining a formed 3D conical silicone electrode point; Step 6, spin-coat the insulating silicone encapsulation layer and dry and solidify it, and then demold the layer to obtain a soft 3D conical silicone neural electrode array with exposed tips.

2. The method for exposing the tip of a soft 3D conical silicone nerve electrode according to claim 1, characterized in that: Step 4 can be replaced by the following steps: Step 4.1, spin coating photoresist to fill the inner groove of the cured soft silicone insulating layer; Step 4.2, irradiating ultraviolet light to cure the photoresist; Step 4.3, using a water-soluble tape to bond the cured photoresist surface, and transferring it together with the soft silicone insulating layer to an acrylic mold having a conical groove inside; Step 4.4, dissolving the water-soluble tape with water; Step 4.5, heating the dimethyl sulfoxide solution to dissolve the photoresist.

3. The method for exposing the tip of a soft 3D conical silicone nerve electrode according to claim 1 or 2, characterized in that: In step 1, the depth of the protrusions and the grooves is 50 to 1000 μm, and the bottom angle of the trapezoid is 10° to 170°.

4. The method for exposing the tip of a soft 3D conical silicone nerve electrode according to claim 1 or 2, characterized in that: The resin male and female molds are made of one or more photocurable resin materials selected from the group consisting of polyurethane acrylate, epoxy acrylate, epoxy resin, and composite photocurable resin.

5. The method for exposing the tip of a soft 3D conical silicone nerve electrode according to claim 1 or 2, characterized in that: In step 2 and step 6, the insulating silicone is made of one or more of polydimethylsiloxane, linear triblock copolymer, and Ecoflex / Dragonskin series platinum-catalyzed silicone rubber.

6. The method for exposing the tip of a soft 3D conical silicone nerve electrode according to claim 1 or 2, characterized in that: In step 4, the acrylic mold with the conical groove is produced by CNC milling and is ground and polished to make its surface smooth.

7. The method for exposing the tip of a soft 3D conical silicone nerve electrode according to claim 1 or 2, characterized in that: In step 5, the conductive silicone is obtained by the following method: multi-walled carbon nanotube powder is uniformly mixed with insulating silicone material, the doping mass ratio is 5% to 30%, and the length of a single carbon nanotube is 2 to 50 μm.

8. The method for exposing the tip of a soft 3D conical silicone nerve electrode according to claim 2, characterized in that: The photoresist used is SU-8 photoresist or AZ photoresist.

9. A method for exposing the tip of a soft 3D conical silicone nerve electrode, characterized in that: The following steps are involved: Step 1, using a light-curing 3D printer to make a conical resin male mold and female mold, wherein the multiple protrusions of the male mold and the multiple grooves of the female mold are all dome-shaped conical structures, the dome sizes of the protrusions and the corresponding grooves are the same, the height and bottom angle of the male mold cone are larger than those of the female mold cone, so as to form a structured gap during alignment and lamination, and the dimensions of the male mold trapezoid and the female mold trapezoid are determined according to the pattern of the neural electrode to be formed; Step 2, spraying a release agent on the surface of the resin convex mold, spin-coating insulating silicone on the surface of the resin concave mold, and then aligning the resin convex mold and the concave mold for pressing; Step 3, solidifying the insulating silicone to obtain a patterned 3D electrode point soft silicone insulating layer, and then removing the resin convex mold; Step 4: Scrape the conductive silicone to fill the conical groove of the resin mold, and dry and solidify it to form a soft silicone conductive area inside the electrode point, thereby obtaining a molded 3D conical silicone electrode point; Step 5, spin-coat an insulating silicone encapsulation layer and dry and solidify it, and then demold the layer to obtain a soft 3D conical silicone neural electrode array with exposed tips.

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