A high-precision patterned hydrogel, its preparation method, and flexible electronic devices

Abstract

This invention discloses a high-precision patterned hydrogel, its preparation method, and a flexible electronic device. The preparation method of the high-precision patterned hydrogel includes the following steps: using a buffer solution containing polyethylene glycol thiol derivatives and hydrogen peroxide as a prepolymer solution (prepolymer solution 1), applying the prepolymer solution 1 to the surface of a substrate, and reacting to obtain a substrate with a thin film; using an aqueous solution containing a monoene water-soluble monomer, a diene water-soluble monomer, a water-soluble photoinitiator, and a polymerization inhibitor as a prepolymer solution (prepolymer solution 2), immersing the substrate with the first thin film in the prepolymer solution 2; after immersion, washing and solvent removal to obtain a substrate with a dry film; photolithographically patterning the substrate with the dry film, and then removing unexposed areas with a developer to obtain the high-precision patterned hydrogel. This invention can effectively improve the precision of the patterned hydrogel, while also giving the high-precision patterned hydrogel high biocompatibility and ion permeability.

Description

Technical Field

[0001] This invention relates to a high-precision patterned hydrogel, its preparation method, and flexible electronic devices, belonging to the fields of flexible electronics and micro / nano fabrication technology. Background Technology

[0002] Hydrogels are materials with a three-dimensional hydrophilic polymer network structure capable of storing large amounts of water. Due to their excellent biocompatibility and Young's modulus close to that of human tissue, they are widely used in biomedicine, drug delivery, tissue engineering, and soft robotics. The loose network structure of hydrogels provides strong support for their excellent molecular / ionic permeability, including that of gas molecules, drug molecules, and salt ions. This property expands their applications in the human body as human-computer interaction interfaces.

[0003] Hydrogel patterning is a crucial technique in flexible electronics, encompassing both planar and three-dimensional patterning. Currently, the most widely used patterning method is photoinitiation. By adding a photoinitiator to the hydrogel prepolymer, a robust three-dimensional network structure is formed through a large number of free radical chain reactions after absorbing light of the corresponding wavelength. Common methods include stereolithography and two-photon printing. However, these methods often have drawbacks. Due to the high water content in the hydrogel prepolymer, the free radicals generated by photoinitiation have a high migration speed and distance, often resulting in low channel fidelity, significant channel residue, and severe edge overexposure, leading to low precision (approximately 50-100 μm). Alternatively, reducing the water content in the hydrogel prepolymer and significantly increasing the photoinitiator and monomer content can utilize the principle that the high concentration of free radicals generated after photoinitiation can rapidly terminate chains, reducing the free radical migration distance and increasing exposure precision (maskless lithography: 1-5 μm; two-photon lithography: <1 μm). However, this method is often accompanied by decreased biocompatibility, extremely high network density, and extremely slow lithography speed (two-photon lithography). Therefore, traditional systems cannot simultaneously meet the requirements of biocompatibility and device miniaturization for related applications in the human body.

[0004] In summary, to better realize the functions of wearable devices, it is necessary to design new high-precision patterned hydrogel systems that have good biocompatibility, loose pore structures that allow drug molecules and ions to pass through, and adapt to miniaturization requirements down to 5 μm. Summary of the Invention

[0005] To address the aforementioned technical problems, the present invention aims to provide a high-precision patterned hydrogel, its preparation method, and a flexible electronic device. The present invention effectively improves the precision of patterned hydrogels while simultaneously enabling the high-precision patterned hydrogel to possess high biocompatibility and ion permeability.

[0006] To achieve the above objectives, the first aspect of the present invention provides a method for preparing a high-precision patterned hydrogel, comprising the following steps:

[0007] S1: A buffer solution containing polyethylene glycol thiol derivatives and hydrogen peroxide is used as prepolymer solution No. 1. The prepolymer solution No. 1 is applied to the surface of the substrate. After reaction, a substrate with a thin film is obtained.

[0008] S2: An aqueous solution containing monoene water-soluble monomers, diene water-soluble monomers, water-soluble photoinitiators and polymerization inhibitors is used as prepolymer solution No. 2. The substrate with the first film is immersed in the prepolymer solution No. 2. After immersion, the substrate with a dry film is obtained after washing and solvent removal.

[0009] S3: The substrate with the dry film is patterned by photolithography, and the unexposed areas are removed with a developer to obtain the high-precision patterned hydrogel.

[0010] According to a specific embodiment of the present invention, preferably, the substrate includes one or more of glass, silicon wafers, and flexible transparent parylene films.

[0011] According to a specific embodiment of the present invention, preferably, the preparation method further includes the following steps before step S1: S0: pretreatment of the substrate, wherein the pretreatment includes solution pretreatment or vacuum pretreatment, and the pretreatment uses a silane coupling agent. More preferably, the silane coupling agent includes γ-methacryloyloxypropyltrimethoxysilane, etc.

[0012] More preferably, in step S0, the solution pretreatment includes: immersing the substrate in a pretreatment solution, reacting after immersion, and then drying to obtain a pretreated substrate; the pretreatment solution includes a solution of γ-methacryloxypropyltrimethoxysilane. Specifically, the γ-methacryloxypropyltrimethoxysilane solution is a solution of γ-methacryloxypropyltrimethoxysilane in water and isopropanol, wherein the volume ratio of γ-methacryloxypropyltrimethoxysilane, water, and isopropanol is 1:(50-100):(50-100). The ratio of the substrate to the pretreatment solution can be conventionally adjusted by those skilled in the art, as long as the substrate is completely immersed in the pretreatment solution. The immersion time can be 15 hours. The reaction can be carried out by standing in air for 15 minutes. Before drying, the substrate can be rinsed with isopropanol and then dried. Before performing the above pretreatment, the substrate can also be cleaned with water and / or ethanol.

[0013] More preferably, in step S0, the vacuum pretreatment includes: dropping an appropriate amount of γ-methacryloxypropyltrimethoxysilane into an unsealed container, placing the container and the substrate together in a vacuum-sealed environment, and treating under vacuum at 80–100°C for a suitable time to obtain the pretreated substrate. Specifically, the amount of γ-methacryloxypropyltrimethoxysilane dropped into the unsealed container can be adjusted by those skilled in the art according to the area of ​​the substrate; for example, 200–500 μl of γ-methacryloxypropyltrimethoxysilane can be dropped into the unsealed container. The vacuum-sealed environment can be provided by a vacuum oven. The vacuum level can be 10–200 Pa. The treatment time under vacuum at 80–100°C is preferably sufficient to allow the γ-methacryloxypropyltrimethoxysilane to volatilize and grow on the substrate surface, for example, 1–3 hours. Before performing the above pretreatment, the substrate can also be cleaned with water and / or ethanol.

[0014] According to a specific embodiment of the present invention, preferably, in step S1, the polyethylene glycol thiol derivative includes a two-, four-, or eight-armed macromolecular polyethylene glycol derivative with a thiol terminal group. More preferably, the molecular weight of the polyethylene glycol thiol derivative is 1000 to 10000. It should be noted that, in the present invention, the unit of molecular weight is Dalton (Da). Specifically, the polyethylene glycol thiol derivative includes a four-armed polyethylene glycol thiol. More preferably, the molecular weight of the four-armed polyethylene glycol thiol is 5000.

[0015] According to a specific embodiment of the present invention, preferably, in step S1, the No. 1 prepolymer solution is prepared by the following steps: dissolving a polyethylene glycol thiol derivative in a buffer solution to obtain a first solution with a polyethylene glycol thiol derivative concentration of 0.05 g / ml to 0.1 g / ml; diluting an aqueous hydrogen peroxide solution with the buffer solution to obtain a second solution with a hydrogen peroxide mass concentration of 1% to 5%; and mixing the first solution and the second solution uniformly at a volume ratio of 3:(1 to 2) to obtain the No. 1 prepolymer solution. More preferably, the pH value of the buffer solution is 7.0 to 8.0, more preferably 7.5, and the concentration is 0.001 M to 0.1 M, more preferably 0.01 M. Specifically, the buffer solution is an aqueous solution prepared from sodium dihydrogen phosphate and disodium hydrogen phosphate. The mass concentration of the aqueous hydrogen peroxide solution can be 30%.

[0016] According to a specific embodiment of the present invention, preferably, in step S1, after the preparation of the No. 1 prepolymer solution is completed, the No. 1 prepolymer solution is applied to the surface of the substrate within 1 minute. After application, it is allowed to stand for 5 to 15 minutes to allow the reaction to be complete, thereby obtaining the substrate with the thin film. This process of allowing the reaction to proceed can be carried out at room temperature.

[0017] According to a specific embodiment of the present invention, preferably, in step S2, the monoolefin water-soluble monomer includes one or more of acrylic acid, acrylamide, vinylpyrrolidone, and ethyl methacrylate.

[0018] According to a specific embodiment of the present invention, preferably, in step S2, the diene-based water-soluble monomer includes a small-molecule polyethylene glycol derivative with a vinyl end group. More preferably, the molecular weight of the diene-based water-soluble monomer is 400-700. Specifically, the diene-based water-soluble monomer includes polyethylene glycol diacrylate (PEGDA) and the like. Further preferably, the molecular weight of the polyethylene glycol diacrylate is 400-700.

[0019] According to a specific embodiment of the present invention, preferably, in step S2, the water-soluble photoinitiator includes one or two of 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylphenylacetone and phenyl-2,4,6-trimethylbenzoylphosphinic acid lithium (LAP). 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylphenylacetone and phenyl-2,4,6-trimethylbenzoylphosphinic acid lithium can be used to absorb light in the 365nm and 405nm wavelength bands, respectively.

[0020] According to a specific embodiment of the present invention, preferably, in step S2, the polymerization inhibitor includes one or more of phenolic compounds and nitrogen-containing heterocyclic compounds. More preferably, the polymerization inhibitor includes one or more of 4-methylphenol, benzothiazole, and hydroquinone.

[0021] According to a specific embodiment of the present invention, preferably, in step S2, the mass ratio of the monoene water-soluble monomer, the diene water-soluble monomer, the water-soluble photoinitiator, and the polymerization inhibitor in the prepolymer solution No. 2 is 1:(0.1-1):(0.2-0.5):(0.002-0.005). More preferably, the mass ratio of the monoene water-soluble monomer, the diene water-soluble monomer, the water-soluble photoinitiator, the polymerization inhibitor, and water in the prepolymer solution No. 2 is 1:(0.1-1):(0.2-0.5):(0.002-0.005):(10-100).

[0022] According to a specific embodiment of the present invention, preferably, in step S2, the soaking time is 6 to 24 hours.

[0023] According to a specific embodiment of the present invention, preferably, in step S2, the solvent removal method includes heating at 30°C to 70°C for 1 to 10 minutes. Specifically, the solvent removal method may include heating at 30°C to 70°C for 5 to 10 minutes; or, after air drying for 20 to 40 minutes and / or purging with high-purity nitrogen for 1 to 3 minutes, heating at 40°C to 70°C for 1 to 5 minutes. Washing removes residual monomers from the film surface, and then performing the above solvent removal step removes residual hydrogen peroxide and reduces the free radical migration rate, thereby increasing exposure accuracy.

[0024] According to a specific embodiment of the present invention, preferably, in step S3, the photolithography is maskless photolithography. More preferably, the photolithography is performed under light with a wavelength of 365nm or 405nm.

[0025] According to a specific embodiment of the present invention, preferably, in step S3, the developer comprises a tris(2-carboxyethyl)phosphine hydrochloride solution. Specifically, the concentration of the tris(2-carboxyethyl)phosphine hydrochloride solution can be 50 mM.

[0026] According to a specific embodiment of the present invention, preferably, in step S3, the process of removing the unexposed areas with a developer includes: immersing the photolithographically etched substrate with a dry film in a developer for 5 to 30 minutes to remove the unexposed areas. The specific development time can be determined according to the thickness of the dry film.

[0027] A second aspect of the present invention provides a high-precision patterned hydrogel, which is prepared by the above-described method for preparing a high-precision patterned hydrogel.

[0028] According to a specific embodiment of the present invention, preferably, the high-precision patterned hydrogel comprises an interwoven first polymer network and a second polymer network. The first polymer network comprises a polymer network formed at least of polyethylene glycol thiol derivatives, and the second polymer network comprises a polymer network formed at least of monoene water-soluble monomers and diene water-soluble monomers. It should be noted that the interweaving refers to the first polymer network and the second polymer network interpenetrating each other.

[0029] According to a specific embodiment of the present invention, preferably, the first polymer network comprises a polymer network formed by reacting a buffer solution containing polyethylene glycol thiol derivatives and hydrogen peroxide as a No. 1 prepolymer solution.

[0030] According to a specific embodiment of the present invention, preferably, the second polymer network comprises a polymer network formed by reacting an aqueous solution containing a monoene water-soluble monomer, a diene water-soluble monomer, a water-soluble photoinitiator, and a polymerization inhibitor as a No. 2 prepolymer solution.

[0031] A third aspect of the present invention provides a flexible electronic device comprising the aforementioned high-precision patterned hydrogel. More preferably, in the flexible electronic device, the high-precision patterned hydrogel serves as an ion channel.

[0032] The present invention has at least the following beneficial effects:

[0033] This invention produces a high-precision patterned hydrogel by micro-nano fabrication on a pretreated substrate. A polyethylene glycol thiol derivative is used as the basic polymer backbone network (i.e., the first polymer network). Monomers and photoinitiators that can form a second polymer network are introduced via solution exchange. The reversible nature of cross-linked disulfide bonds breaking under the action of a developer is utilized to wash away unexposed portions, forming the high-precision patterned hydrogel. This invention avoids the low fidelity of traditional photolithographic hydrogels and the problem of excessively high monomer and initiator concentrations in some high-precision photolithographic hydrogel systems. The high-precision patterned hydrogel of this invention exhibits good biocompatibility, with a water absorption rate of up to 250%. It has a porous structure that allows drug molecules and ions to pass through, facilitating the exchange of molecules and ions between the polymer network and the external environment, resulting in high ion permeability. The photolithographic precision of the high-precision patterned hydrogel of this invention can reach 4 μm. Simultaneously, the exposed pattern of this invention is relatively clean, with minimal residue in the developed area. Moreover, this invention uses a traditional planar exposure process, offering the advantage of high photolithography speed. The high-precision patterned hydrogel of this invention can be applied to flexible electronic devices, especially as ion channels. For example, this invention can be used as an adhesive interface layer in implantable devices, such as the electrolyte layer in electrochemical transistors, ensuring both interfacial contact and effective ion exchange. This invention is expected to be widely applied to various flexible implantable devices as one of the technologies for preparing customized patterned adhesive layers. In summary, this invention solves the incompatibilities of existing patterned hydrogels in terms of loose pore structure, biocompatibility, and precision, and is well-matched with implantation systems. Attached Figure Description

[0034] Figure 1 This is a schematic diagram of the high-precision patterned hydrogel provided in Embodiment 1 of the present invention under a light microscope.

[0035] Figure 2 This is provided in Embodiment 1 of the present invention. Figure 1 A schematic diagram of a high-precision patterned hydrogel under a scanning electron microscope.

[0036] Figure 3 This is a schematic diagram of a pattern of a high-precision patterned hydrogel provided in Embodiment 1 of the present invention under a light microscope.

[0037] Figure 4This is a schematic diagram of the patterned hydrogel provided in Comparative Example 1 of the present invention under a light microscope.

[0038] Figure 5 This is a schematic diagram of another pattern of the high-precision patterned hydrogel provided in Embodiment 1 of the present invention under a light microscope.

[0039] Figure 6 This is a schematic diagram of the high-precision patterned hydrogel provided in Embodiment 2 of the present invention under an optical microscope.

[0040] Figure 7 The results show the biocompatibility of the blank control group and the high-precision patterned hydrogel provided in Example 1 after 7 days.

[0041] Figure 8 Cell survival of the high-precision patterned hydrogel provided in Example 1 on days 1, 3, and 7.

[0042] Figure 9 The results show the water absorption properties of the high-precision patterned hydrogel provided in Example 1.

[0043] Figure 10 This is a schematic diagram of a vertical electrochemical transistor used for ion permeability testing.

[0044] Figure 11 The electrochemical transistor assembled with high-precision patterned hydrogel in Example 1 is shown as an electrical transfer characteristic curve when it operates in a 0.1M standard sodium chloride solution.

[0045] Figure 12 The porous network structure exhibited by the high-precision patterned hydrogel of Example 1 after freeze-drying. Detailed Implementation

[0046] To provide a clearer understanding of the technical features, objectives, and beneficial effects of the present invention, the present invention will now be described in detail below, but this should not be construed as limiting the scope of the invention.

[0047] It should be noted that, unless otherwise specified, all technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0048] Unless otherwise specified, all raw materials, reagents, instruments and equipment used in this invention can be purchased from the market or prepared by existing methods.

[0049] It should be understood that the terms “comprising,” “including,” and / or “containing” as used herein specify the presence of the stated features, integers, steps, components, or combinations thereof, but do not exclude the presence or addition of one or more other features, integers, steps, components, or combinations thereof.

[0050] The endpoints and any values ​​of the ranges disclosed in this invention are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed in this invention.

[0051] Example 1

[0052] A pretreatment solution of γ-methacryloyloxypropyltrimethoxysilane:pure water:isopropanol with a volume ratio of 1:100:100 was prepared and allowed to stand for 2 hours. A glass substrate with a planar dimension of 2 cm × 1.5 cm was immersed in the pretreatment solution. Before immersion, the glass was cleaned with pure water and / or ethanol. After immersion for 15 minutes, the substrate was removed and allowed to stand in air for 15 minutes to allow the reaction to complete. It was then rinsed with isopropanol and dried with nitrogen to obtain the pretreated substrate, which was then stored. The pretreated substrate needed to undergo photolithography within 30 hours.

[0053] Prepare the required solutions. Dissolve the four-armed polyethylene glycol thiol with a molecular weight of 5000 in a 0.01M (mol / L) sodium dihydrogen phosphate-disodium hydrogen phosphate buffer solution at pH 7.5, and sonicate for 3-5 minutes until completely dissolved and defoamed to obtain the first solution with a four-armed polyethylene glycol thiol concentration of 0.1 g / ml. Dilute a 30% (w / w) aqueous solution of hydrogen peroxide with a 0.01M (w / w) sodium dihydrogen phosphate-disodium hydrogen phosphate buffer solution at pH 7.5 to obtain a 1% (w / w) hydrogen peroxide buffer solution as the second solution. Mix 0.1 g of acrylic acid, 0.1 g of PEGDA (molecular weight 400-700), 0.025 g of LAP, and 0.25 mg of 4-methylphenol in 9.8 g of pure water, and sonicate for 10 minutes until all components are completely dissolved and evenly dispersed to obtain the second prepolymer solution.

[0054] Take 12 μl of the first solution and 8 μl of the second solution, and mix them evenly for 1 minute to obtain prepolymer solution No. 1. Quickly aspirate prepolymer solution No. 1 and drop it onto the pretreated substrate, then cover the surface with a layer of hydrophobic PET, ensuring there are no air bubbles under the PET and that prepolymer solution No. 1 contacts the hydrophobic surface of the PET. Let it stand for 8 minutes to allow the reaction to complete, then peel off the hydrophobic PET to obtain the substrate with the film. The thickness of the obtained film is 66.7 μm.

[0055] The substrate with the film was immersed in prepolymer solution No. 2 overnight (about 12 hours) to allow the monomers and photoinitiators in prepolymer solution No. 2 to be completely exchanged into the film. Then the substrate was removed, rinsed with pure water to remove residual monomers on the surface, dried, and then heated at 50°C for 5 minutes to remove residual hydrogen peroxide and water, resulting in a substrate with a dry film.

[0056] The substrate with the dry film was photolithographically lithographically patterned using a maskless lithography machine at a wavelength of 405 nm. After that, it was immersed in a 50 mM tris(2-carboxyethyl)phosphine hydrochloride solution for development for 30 minutes. Then, it was removed and washed with pure water to remove the residual developer, resulting in a high-precision patterned hydrogel.

[0057] The high-precision patterned hydrogel prepared in this embodiment appears as follows under a light microscope: Figure 1 As shown, under a scanning electron microscope Figure 2 As shown; high-precision patterned hydrogels with different patterns obtained by adjusting the photolithography pattern are displayed under a light microscope as follows. Figure 3 and Figure 5 As shown in the figure, the photolithographic precision of the high-precision patterned hydrogel prepared in this embodiment can reach 4 μm. After soaking the prepared high-precision patterned hydrogel in water for 2–3 hours until complete water absorption, it was frozen in liquid nitrogen for half an hour, then removed and dried in a freeze dryer for 1 day. The resulting porous network structure is shown in the figure. Figure 12 As shown. This high-precision patterned hydrogel comprises an interpenetrating first polymer network and a second polymer network. The first polymer network comprises a polymer network formed by at least four-arm polyethylene glycol thiols, and the second polymer network comprises a polymer network formed by at least acrylic acid and PEGDA.

[0058] Example 2

[0059] This embodiment is basically the same as Example 1, except that the acrylic acid in the prepolymer solution No. 2 is replaced with N-vinylpyrrolidone, while the amount remains the same; everything else is the same as in Example 1. The high-precision patterned hydrogel prepared in this embodiment appears as shown under a light microscope... Figure 6 As shown. The photolithographic precision of the high-precision patterned hydrogel prepared in this embodiment can reach 5 μm.

[0060] Example 3

[0061] This embodiment is basically the same as Embodiment 1, except that the ratio of the first solution to the second solution is changed to 15 μl and 5 μl, respectively. All other aspects are the same as in Embodiment 1. The photolithographic precision of the high-precision patterned hydrogel prepared in this embodiment can reach 5 μm.

[0062] Comparative Example 1

[0063] Mix 0.2g acrylic acid, 0.02g PEGDA (molecular weight 400-700), 1g gelatin, 0.04g 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylphenylacetone, 0.0025g 4-methylphenol, and 1.8g pure water. Heat at 70°C for 2-3 hours until the gelatin is completely dissolved and evenly dispersed to obtain a prepolymer solution. Spin-coat the prepolymer solution onto a silicon wafer at 3000 rpm, then cover it with a layer of hydrophobic PET, ensuring no air bubbles under the PET and that the prepolymer solution contacts the hydrophobic surface of the PET. Expose the PET-coated substrate to a 365nm mask lithography machine for 20 seconds, then wash away unreacted areas with pure water to obtain a patterned hydrogel.

[0064] The patterned hydrogel prepared in this comparative example appears as follows under a light microscope: Figure 4 As shown, there are many residual particles at the channel, resulting in lower accuracy. By... Figure 4 and Figure 5 The comparison shows that the high-precision patterned hydrogel with the same pattern prepared in Example 1 has less residue at the channels. Furthermore, this comparative example changed the polymerization system, using gelatin instead of the polyethylene glycol thiol derivative used in the examples. This resulted in the prepolymer liquid in this comparative example failing to solidify after being coated onto the substrate surface. Therefore, this comparative example requires a PET coating on the substrate during photolithography. If the PET is removed, the prepolymer liquid will quickly agglomerate into droplets due to the high surface tension, making it impossible to maintain a uniform thickness on the substrate surface.

[0065] Comparative Example 2

[0066] This comparative example is essentially the same as Example 1, except that the four-armed polyethylene glycol thiol with a molecular weight of 5000 is replaced with polyethylene glycol with a molecular weight of 5000, while the amount remains the same. The preparation steps are also the same as in Example 1. The results show that when the No. 1 prepolymer droplet is placed on the pretreated substrate and covered with hydrophobic PET, it fails to form a solid after standing.

[0067] Comparative Example 3

[0068] This comparative example is basically the same as Example 1, except that PEGDA was not added to the prepolymer solution No. 2, while the remaining components and amounts were the same as in Example 1. The preparation steps were also the same as in Example 1. The results showed that the hydrogel could not be formed after photolithography and could not be patterned.

[0069] Comparative Example 4

[0070] This comparative example is basically the same as Example 1, except that LAP was not added to the prepolymer solution No. 2, while the remaining components and amounts were the same as in Example 1. The preparation steps were also the same as in Example 1. The results showed that the hydrogel could not be formed after photolithography and could not be patterned.

[0071] Comparative Example 5

[0072] This comparative example is basically the same as Example 1, except that the sample soaked overnight in prepolymer solution No. 2 was taken out and directly photolithographically etched without heating. The remaining components and amounts are the same as in Example 1. The preparation steps are also the same as in Example 1. The results show that the patterned hydrogel obtained after photolithography has severe residue at the channels and low precision.

[0073] Test case

[0074] The patterned hydrogels provided in the above embodiments were subjected to tests for biocompatibility, water absorption, and ion permeability. Because the precision of the comparative examples or the patterned hydrogels was too low, or because patterned hydrogels could not be prepared, the biocompatibility, water absorption, and ion permeability of these comparative examples were not tested.

[0075] The biocompatibility testing method included: patterned hydrogels were immersed in HT22 (mouse hippocampal neurons) culture medium and cultured at 37°C for 24 hours. The extract was then used as the experimental group, while HT22 culture medium without extract served as the blank control group. HT22 cells were seeded in 48-well plates and cultured for 24 hours to allow them to adhere. The experimental group was then replaced with the extract culture medium, and the blank group with the culture medium without extract. Cells were cultured at 37°C and 5% CO2 for 1, 3, and 7 days, and cell proliferation was assessed using the CCK-8 assay. The biocompatibility results of the blank control group and the high-precision patterned hydrogel used in Example 1 after 7 days are as follows: Figure 7 As shown in the figure. Cell proliferation results of extracts at different concentrations are as follows. Figure 8 As shown, the patterned hydrogel of Example 1 exhibits excellent biocompatibility.

[0076] The water absorption test method includes: measuring the thickness of the dry gel before water absorption and the thickness of the wet gel after water absorption using a step tester, and obtaining the water absorption rate by (wet gel thickness - dry gel thickness) ÷ dry gel thickness × 100%. The dry gel used in this test is a patterned hydrogel obtained by heat drying. The water absorption results of the high-precision patterned hydrogel in Example 1 are as follows: Figure 9 As shown, the hydrogel of Example 1 has a water absorption rate of 200%–250%, and the comparison of transverse and longitudinal deformations indicates that the main water absorption direction is longitudinal. The hydrogels of Examples 2 and 3 also have a water absorption rate of 200%–250%, exhibiting high water absorption as well. The water absorption results verify that the hydrogels of each example have a loose porous structure, allowing drug molecules and ions to pass through.

[0077] Methods for testing ion permeability include: assembly such as Figure 10A vertical-type electrochemical transistor with the structure shown was tested to determine the ion permeability of the patterned hydrogel. This vertical-type electrochemical transistor includes a drain circuit, an organic semiconductor, a source circuit, a patterned hydrogel (i.e., a photolithographic hydrogel), a parylene film, a standard sodium chloride solution, and a gate. Figure 11 The electrochemical transistor assembled with high-precision patterned hydrogel in Example 1 operates in a 0.1M standard sodium chloride solution, and the electrical transfer characteristic curve shows that the hydrogel of Example 1 has good ion permeability, thereby providing sufficient ions for the operation of the electrochemical transistor.

Claims

1. A method for preparing a high-precision patterned hydrogel, comprising the following steps: S1: applying a buffer solution containing a polyethylene glycol thiol derivative and hydrogen peroxide as a first prepolymer solution to the surface of a substrate, and obtaining a substrate with a film after reaction; S2: immersing the substrate with the film in a water-soluble solution containing a mono-olefinic water-soluble monomer, a di-olefinic water-soluble monomer, a water-soluble photoinitiator and a polymerization inhibitor as a second prepolymer solution, and obtaining a substrate with a dry film after washing and removing the solvent after completion of the immersion; S3: performing photolithography on the substrate with the dry film to pattern, and removing the unexposed areas with a developer to obtain the high-precision patterned hydrogel. The substrate comprises one or more than two of glass, a silicon wafer and a flexible transparent parylene film. The method further comprises, before step S1, S0: pretreating the substrate, wherein the pretreatment comprises solution pretreatment or vacuum pretreatment, and the pretreatment uses a silane coupling agent. In step S0, the silane coupling agent comprises γ-methacryloxypropyltrimethoxysilane. In step S1, the polyethylene glycol thiol derivative comprises a derivative of a two-armed, four-armed or eight-armed macromolecular polyethylene glycol with a thiol group at the end; and the molecular weight of the polyethylene glycol thiol derivative is 1000-10000. In step S1, the polyethylene glycol thiol derivative comprises a four-armed polyethylene glycol thiol. In step S1, the first prepolymer solution is prepared by the following steps: dissolving the polyethylene glycol thiol derivative in a buffer solution to obtain a first solution with a polyethylene glycol thiol derivative concentration of 0.05 g / ml-0.1 g / ml; diluting an aqueous hydrogen peroxide solution with a buffer solution to obtain a second solution with a hydrogen peroxide mass concentration of 1-5%; and mixing the first solution and the second solution uniformly at a volume ratio of 3: (1-2) to obtain the first prepolymer solution. The buffer solution has a pH of 7.0-8.0 and a concentration of 0.001 M-0.1 M. In step S2, the mono-olefinic water-soluble monomer comprises one or more than two of acrylic acid, acrylamide, vinyl pyrrolidone and ethyl methacrylate. In step S2, the di-olefinic water-soluble monomer comprises a derivative of a small-molecular polyethylene glycol with a vinyl group at the end; and the molecular weight of the di-olefinic water-soluble monomer is 400-700. In step S2, the di-olefinic water-soluble monomer comprises polyethylene glycol diacrylate. In step S2, the water-soluble photoinitiator comprises one or more than two of 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone and lithium phenyl-2,4,6-trimethylbenzoylphosphinate. In step S2, the polymerization inhibitor comprises one or more than two of a phenolic compound and a nitrogen-containing heterocyclic compound. In step S2, the polymerization inhibitor comprises one or more than two of 4-methylphenol, benzothiazole and hydroquinone. ​ ​ ​ 2. The method of preparing a high precision patterned hydrogel according to claim 1, wherein, ​ 3. The method of claim 1, wherein the high-precision patterned hydrogel is prepared by a method comprising: ​ 4. The method of claim 3, wherein the high precision patterned hydrogel is prepared by, ​ 5. The method of claim 1, wherein the high-precision patterned hydrogel is prepared by a method comprising: ​ 6. The method of claim 5, wherein the high precision patterned hydrogel is prepared by, ​ 7. The method of preparing a high precision patterned hydrogel according to claim 1, wherein, ​ ​ ​ 8. The method of claim 1, wherein, ​ 9. The method of claim 1, wherein, ​ 10. The method of claim 9, wherein, ​ 11. The method of claim 1, wherein the high precision patterned hydrogel is prepared by, ​ 12. The method of claim 1, wherein, ​ 13. The method of claim 12, wherein the high precision patterned hydrogel is prepared by, ​ 14. The method of claim 1, wherein the high precision patterned hydrogel is prepared by, In step S2, the mass ratio of the mono-olefinic water-soluble monomer, the di-olefinic water-soluble monomer, the water-soluble photoinitiator and the polymerization inhibitor in the No. 2 prepolymer solution is 1:(0.1-1):(0.2-0.5):(0.002-0.005).

15. The method of claim 14, wherein the high precision patterned hydrogel is prepared by, In step S2, the mass ratio of the mono-olefinic water-soluble monomer, the di-olefinic water-soluble monomer, the water-soluble photoinitiator, the polymerization inhibitor and water in the No. 2 prepolymer solution is 1:(0.1-1):(0.2-0.5):(0.002-0.005):(10-100).

16. The method of claim 1, wherein, In step S2, the soaking time is 6-24 hours.

17. The method of preparing a high precision patterned hydrogel according to claim 1, wherein, In step S3, the photolithography is maskless photolithography; the photolithography is performed under light of a wavelength of 365 nm or 405 nm. The developer comprises a solution of tris(2-carboxyethyl)phosphine hydrochloride.

18. A high-precision patterned hydrogel prepared by the method for preparing a high-precision patterned hydrogel according to any one of claims 1-17.

19. A flexible electronic device comprising the high-precision patterned hydrogel according to claim 18; in the flexible electronic device, the high-precision patterned hydrogel is used as an ion channel.

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