High-precision patterned hydrogel and preparation method therefor, and flexible electronic device

Abstract

Disclosed in the present invention are a high-precision patterned hydrogel and a preparation method therefor, and a flexible electronic device. The preparation method for the high-precision patterned hydrogel comprises the following steps: using a buffer solution containing a polyethylene glycol thiol derivative and hydrogen peroxide as a first prepolymer solution, applying same onto the surface of a substrate, and after reaction, obtaining a substrate having a 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 second prepolymer solution, immersing the substrate having the film in the second prepolymer solution, and after immersion, performing washing and solvent removal, so as to obtain a substrate having a dry film; and subjecting the substrate having the dry film to photolithography for patterning, and then removing unexposed regions with a developer, so as to obtain a high-precision patterned hydrogel.

Description

A high-precision patterned hydrogel, its preparation method, and flexible electronic devices 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 can be formed through a large number of free radical chain reactions after absorbing light of the corresponding wavelength. Common methods include stereolithography and two-photon lithography. However, these methods often have drawbacks. Due to the large amount of water 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 film is immersed in the prepolymer solution No. 2. After immersion, the substrate with the 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] 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.

[0011] A third aspect of the present invention provides a flexible electronic device comprising the above-described high-precision patterned hydrogel.

[0012] The present invention has at least the following beneficial effects:

[0013] 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

[0014] Figure 1 is a schematic diagram of the high-precision patterned hydrogel provided in Embodiment 1 of the present invention under an optical microscope.

[0015] Figure 2 is a schematic diagram of the high-precision patterned hydrogel in Figure 1 provided in Embodiment 1 of the present invention under a scanning electron microscope.

[0016] Figure 3 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.

[0017] Figure 4 is a schematic diagram of the patterned hydrogel provided in Comparative Example 1 of the present invention under a light microscope.

[0018] Figure 5 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.

[0019] Figure 6 is a schematic diagram of the high-precision patterned hydrogel provided in Embodiment 2 of the present invention under an optical microscope.

[0020] Figure 7 shows the biocompatibility results of the blank control group and the high-precision patterned hydrogel provided in Example 1 after 7 days.

[0021] Figure 8 shows the cell survival of the high-precision patterned hydrogel provided in Example 1 on days 1, 3, and 7.

[0022] Figure 9 shows the water absorption results of the high-precision patterned hydrogel provided in Example 1.

[0023] Figure 10 is a schematic diagram of the structure of a vertical electrochemical transistor used for ion permeability testing.

[0024] Figure 11 shows the electrochemical transistor assembled with high-precision patterned hydrogel in Example 1 when it operates in a 0.1M standard sodium chloride solution.

[0025] Figure 12 shows the porous network structure of the high-precision patterned hydrogel of Example 1 after freeze-drying. Detailed Implementation

[0026] 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.

[0027] 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.

[0028] 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.

[0029] 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.

[0030] 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.

[0031] According to a specific embodiment of the first aspect of the present invention, the present invention provides a method for preparing a high-precision patterned hydrogel, which includes the following steps:

[0032] 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.

[0033] 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 film is immersed in the prepolymer solution No. 2. After immersion, the substrate with the dry film is obtained after washing and solvent removal.

[0034] 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.

[0035] In some embodiments, the substrate includes one or more of glass, silicon wafers, and flexible transparent parylene films.

[0036] In some embodiments, the preparation method further includes, prior to step S1: S0: pretreatment of the substrate, the pretreatment including solution pretreatment or vacuum pretreatment, wherein the pretreatment employs a silane coupling agent. Preferably, the silane coupling agent includes γ-methacryloyloxypropyltrimethoxysilane, etc.

[0037] 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. The substrate can be rinsed with isopropanol first and then dried. Before performing the above pretreatment, the substrate can also be cleaned with water and / or ethanol.

[0038] 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.

[0039] In some embodiments, in step S1, the polyethylene glycol thiol derivative comprises a two-, four-, or eight-armed macromolecular polyethylene glycol derivative with a thiol terminal group. Preferably, the molecular weight of the polyethylene glycol thiol derivative is 1000 to 10000. It should be noted that, in this invention, the unit of molecular weight is Dalton (Da). Specifically, the polyethylene glycol thiol derivative comprises a four-armed polyethylene glycol thiol. More preferably, the molecular weight of the four-armed polyethylene glycol thiol is 5000.

[0040] In some embodiments, 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. 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%.

[0041] In some embodiments, 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 complete, thereby obtaining the substrate with the film. This standing process for reaction can be carried out at room temperature.

[0042] In some embodiments, in step S2, the monoolefin water-soluble monomer includes one or more of acrylic acid, acrylamide, vinylpyrrolidone, and ethyl methacrylate.

[0043] In some embodiments, in step S2, the diene-based water-soluble monomer includes a small-molecule polyethylene glycol derivative with a vinyl end group. 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. More preferably, the molecular weight of the polyethylene glycol diacrylate is 400-700.

[0044] In some embodiments, in step S2, the water-soluble photoinitiator includes one or two of 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylphenylacetone and lithium phenyl-2,4,6-trimethylbenzoylphosphinic acid (LAP). 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylphenylacetone and lithium phenyl-2,4,6-trimethylbenzoylphosphinic acid can be used to absorb light in the 365 nm and 405 nm wavelength bands, respectively.

[0045] In some embodiments, in step S2, the polymerization inhibitor includes one or more of phenolic compounds and nitrogen-containing heterocyclic compounds. Preferably, the polymerization inhibitor includes one or more of 4-methylphenol, benzothiazole, and hydroquinone.

[0046] In some embodiments, 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). 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).

[0047] In some embodiments, the soaking time in step S2 is 6 to 24 hours.

[0048] In some embodiments, the solvent removal method in step S2 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 solvent removal step described above removes residual hydrogen peroxide and reduces the free radical migration rate, thereby increasing exposure accuracy.

[0049] In some embodiments, the photolithography in step S3 is maskless photolithography. Preferably, the photolithography is performed under light with a wavelength of 365 nm or 405 nm.

[0050] In some embodiments, in step S3, the developer comprises a tris(2-carboxyethyl)phosphine hydrochloride solution. Specifically, the concentration of the tris(2-carboxyethyl)phosphine hydrochloride solution may be 50 mM.

[0051] In some embodiments, step S3, the process of removing 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 may vary depending on the thickness of the dry film.

[0052] According to a specific embodiment of the second aspect of the present invention, the present invention provides a high-precision patterned hydrogel, which is prepared by the above-described method for preparing a high-precision patterned hydrogel.

[0053] In some embodiments, 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 and second polymer networks being interwoven with each other.

[0054] In some embodiments, the first polymer network comprises a polymer network formed by reacting a buffer solution containing polyethylene glycol thiol derivatives and hydrogen peroxide as a prepolymer solution No. 1.

[0055] In some embodiments, 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 prepolymer solution No. 2.

[0056] According to a specific embodiment of a third aspect of the present invention, the present invention provides a flexible electronic device comprising the above-described high-precision patterned hydrogel.

[0057] In some embodiments, the high-precision patterned hydrogel serves as an ion channel in the flexible electronic device.

[0058] The technical solutions of the present invention are specifically illustrated below through embodiments, but the present invention is not limited to these embodiments. Of course, various modifications can be made within the scope of the key points of the present invention.

[0059] Example 1

[0060] 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.

[0061] 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.

[0062] 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.

[0063] 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.

[0064] 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.

[0065] The high-precision patterned hydrogel prepared in this embodiment is shown in Figure 1 under an optical microscope and Figure 2 under a scanning electron microscope. High-precision patterned hydrogels with different patterns obtained by adjusting the photolithographic pattern are shown in Figures 3 and 5 under an optical microscope. It can be seen that 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, resulting in a porous network structure as shown in Figure 12. This high-precision patterned hydrogel includes an interpenetrating first polymer network and a second polymer network. The first polymer network includes a polymer network formed by at least four-arm polyethylene glycol thiols, and the second polymer network includes a polymer network formed by at least acrylic acid and PEGDA.

[0066] Example 2

[0067] 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 is shown in Figure 6 under a light microscope. The photolithographic precision of the high-precision patterned hydrogel prepared in this embodiment can reach 5 μm.

[0068] Example 3

[0069] 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.

[0070] Comparative Example 1

[0071] 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.

[0072] Figure 4 shows the patterned hydrogel prepared in this comparative example under a light microscope. It can be seen that there is a significant amount of residue at the channels, indicating lower precision. Comparing Figures 4 and 5 reveals that the high-precision patterned hydrogel with the same pattern prepared in Example 1 has less residue at the channels. Furthermore, this comparative example uses a different polymerization system, not the polyethylene glycol thiol derivative used in the previous examples, but gelatin. This results 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 high surface tension, making it impossible to maintain a uniform thickness on the substrate surface.

[0073] Comparative Example 2

[0074] 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.

[0075] Comparative Example 3

[0076] 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.

[0077] Comparative Example 4

[0078] 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.

[0079] Comparative Example 5

[0080] 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.

[0081] Test case

[0082] 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.

[0083] The biocompatibility testing method included: immersing the patterned hydrogel in HT22 (mouse hippocampal neurons) medium at 37°C for 24 hours, then extracting the extract as the experimental group, and using HT22 medium without extract 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 medium, and the blank group with the medium without extract. Cells were cultured at 37°C in a 5% CO2 environment 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 from Example 1 after 7 days are shown in Figure 7. The cell proliferation results with different concentrations of extract are shown in Figure 8, indicating that the patterned hydrogel of Example 1 has excellent biocompatibility.

[0084] 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 heating and drying. The water absorption results of the high-precision patterned hydrogel in Example 1 are shown in Figure 9. It can be seen that the water absorption rate of the hydrogel in Example 1 is 200%–250%, and the comparison of transverse and longitudinal deformation shows that the main water absorption direction is longitudinal. The water absorption rates of the hydrogels in Examples 2 and 3 are both 200%–250%, which also have high water absorption rates. The water absorption results verify that the hydrogels of each example have a loose porous structure, which allows drug molecules and ions to pass through.

[0085] The ion permeability testing method includes assembling a vertical electrochemical transistor with the structure shown in Figure 10 and testing its normal operation to determine the ion permeability of the patterned hydrogel. This vertical 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 shows the electrical transfer characteristic curves of the electrochemical transistor assembled with the high-precision patterned hydrogel of Example 1 when operating in a 0.1M standard sodium chloride solution, demonstrating that the hydrogel of Example 1 possesses good ion permeability, thus providing sufficient ions for the operation of the electrochemical transistor.

[0086] The above description is merely a preferred embodiment of the present invention and is not intended to limit the scope of the substantive technical content of the present invention. The substantive technical content of the present invention is broadly defined within the scope of the claims. Any technical entity or method implemented by others that is completely identical to or an equivalent modification of the claims is considered to be covered within the scope of the claims.

Claims

1. A method for preparing a high-precision patterned hydrogel, comprising the following steps: 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. 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 film is immersed in the prepolymer solution No.

2. After immersion, the substrate with the dry film is obtained after washing and solvent removal. 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.

2. The method for preparing high-precision patterned hydrogel according to claim 1, wherein, The substrate includes one or more of glass, silicon wafers, and flexible transparent parylene films.

3. The method for preparing high-precision patterned hydrogel according to claim 1, wherein, The preparation method further includes the following steps before step S1: S0: pretreatment of the substrate, the pretreatment including solution pretreatment or vacuum pretreatment, the pretreatment using a silane coupling agent.

4. The method for preparing high-precision patterned hydrogel according to claim 3, wherein, In step S0, the silane coupling agent includes γ-methacryloxypropyltrimethoxysilane.

5. The method for preparing high-precision patterned hydrogel according to claim 1, wherein, In step S1, the polyethylene glycol thiol derivative includes a derivative of a macromolecular polyethylene glycol with two, four, or eight arms and a thiol terminal group. And / or, the molecular weight of the polyethylene glycol thiol derivative is 1000 to 10000; And / or, the polyethylene glycol thiol derivative includes a tetra-arm polyethylene glycol thiol.

6. The method for preparing high-precision patterned hydrogel according to claim 1, wherein, In step S1, the No. 1 prepolymer solution is prepared by the following steps: dissolving 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 hydrogen peroxide aqueous solution with a buffer solution to obtain a second solution with a hydrogen peroxide mass concentration of 1% to 5%; 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; the pH value of the buffer solution is 7.0 to 8.0, and the concentration is 0.001 M to 0.1 M.

7. The method for preparing high-precision patterned hydrogel according to claim 1, wherein, In step S2, the monoolefin water-soluble monomer includes one or more of acrylic acid, acrylamide, vinylpyrrolidone, and ethyl methacrylate.

8. The method for preparing high-precision patterned hydrogel according to claim 1, wherein, In step S2, the diene water-soluble monomer includes a small molecule polyethylene glycol derivative with a vinyl end group; And / or, the molecular weight of the diene water-soluble monomer is 400 to 700; And / or, the diene water-soluble monomer includes polyethylene glycol diacrylate.

9. The method for preparing high-precision patterned hydrogel according to claim 1, wherein, In step S2, the water-soluble photoinitiator includes one or both of 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylphenylacetone and phenyl-2,4,6-trimethylbenzoyl lithium phosphinate.

10. The method for preparing high-precision patterned hydrogel according to claim 1, wherein, In step S2, the polymerization inhibitor includes one or more of phenolic compounds and nitrogen-containing heterocyclic compounds; And / or, the polymerization inhibitor includes one or more of 4-methylphenol, benzothiazole, and hydroquinone.

11. The method for preparing high-precision patterned hydrogel according to claim 1, wherein, 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 No. 2 prepolymer solution is 1:(0.1~1):(0.2~0.5):(0.002~0.005); And / or, the mass ratio of monoene water-soluble monomers, diene water-soluble monomers, water-soluble photoinitiators, polymerization inhibitors and water in the No. 2 prepolymer solution is 1:(0.1~1):(0.2~0.5):(0.002~0.005):(10~100).

12. The method for preparing high-precision patterned hydrogel according to claim 1, wherein, In step S2, the soaking time is 6 to 24 hours.

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

14. A high-precision patterned hydrogel, which is prepared by the method of any one of claims 1-13.

15. A flexible electronic device comprising the high-precision patterned hydrogel of claim 14.

16. The flexible electronic device according to claim 15, wherein, The high-precision patterned hydrogel serves as an ion channel.

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