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

Abstract

The invention discloses a high-precision patterned hydrogel, a preparation method thereof and a flexible electronic device. The preparation method of the high-precision patterned hydrogel comprises the following steps: taking a buffer solution containing a polyethylene glycol mercaptan derivative and hydrogen peroxide as a No.1 prepolymerization solution, coating the surface of a substrate with the No.1 prepolymerization solution, and reacting to obtain the substrate with a film; taking 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 pre-polymerization solution, soaking the substrate with the first film in the second pre-polymerization solution, and after soaking is completed, washing and removing the solvent to obtain a substrate with a dry film; and carrying out photoetching on the substrate with the dry film to pattern, and removing an unexposed area by using a developing agent to obtain the high-precision patterned hydrogel. According to the method, the precision of the patterned hydrogel can be effectively improved, and meanwhile, the high-precision patterned hydrogel has relatively high biocompatibility and ion permeability.

Description

Technical Field

[0001] The invention relates to a high-precision patterned hydrogel and a preparation method thereof and a flexible electronic device, belonging to the technical field of flexible electronics and micro-nano processing. Background Art

[0002] Hydrogel is a material with a three-dimensional hydrophilic polymer network structure that can store a large amount of water. It is widely used in biomedicine, drug release, tissue engineering and soft robotics due to its good biocompatibility and Young's modulus close to that of human tissue. The loose network structure of hydrogel provides strong support for its good molecular / ion permeability, including gas molecules, drug molecules and salt ions, which expands its application in the human body as a human-machine interface.

[0003] Hydrogel patterning is an extremely important technical means in the field of flexible electronic technology, including planar patterning and three-dimensional patterning. At present, the most widely used patterning method is the photoinitiator method. By adding a photoinitiator to the hydrogel prepolymer, a large number of free radical chain reactions can be formed to form a strong three-dimensional network structure after absorbing light in the corresponding band. Commonly used methods include stereolithography and two-photon printing. However, these methods often have defects. Due to the presence of a large amount of water in the hydrogel prepolymer, the free radicals generated by photoinitiation have a high migration speed and migration distance. Therefore, there are often problems such as low channel fidelity, a large number of residual channels, and severe edge overexposure, which leads to low precision (about 50-100μm). Alternatively, the water content in the hydrogel prepolymer is reduced, the photoinitiator content and monomer content are greatly increased, and the high concentration of free radicals generated after photoinitiation can quickly terminate the chain, reduce the free radical migration distance, and increase the exposure accuracy (maskless lithography: 1-5μm; two-photon lithography: <1μm). However, this method is often accompanied by decreased biocompatibility, extremely high network density, and extremely slow lithography speed (two-photon lithography). Therefore, the traditional system cannot simultaneously meet the requirements of biocompatibility and device miniaturization for related applications in the human body.

[0004] In summary, in order to better realize the functions of wearable devices, it is necessary to design a new high-precision patterned hydrogel system that has good biocompatibility, a loose pore structure that allows drug molecules and ions to pass through, and adapt to the miniaturization requirements as low as 5μm. Summary of the invention

[0005] In order to solve the above technical problems, the purpose of the present invention is to provide a high-precision patterned hydrogel and a preparation method thereof and a flexible electronic device. The present invention can effectively improve the precision of the patterned hydrogel and at the same time make the high-precision patterned hydrogel have higher biocompatibility and ion permeability.

[0006] In order to achieve the above object, the first aspect of the present invention provides a method for preparing a high-precision patterned hydrogel, which comprises the following steps:

[0007] S1: using a buffer solution containing a polyethylene glycol thiol derivative and hydrogen peroxide as a No. 1 prepolymerization solution, applying the No. 1 prepolymerization solution to the surface of a substrate, and obtaining a substrate having a thin film after reaction;

[0008] S2: using an aqueous solution containing a monoolefin water-soluble monomer, a diene water-soluble monomer, a water-soluble photoinitiator and an inhibitor as a No. 2 prepolymerization solution, immersing the substrate having the first thin film in the No. 2 prepolymerization solution, and after immersion, washing and removing the solvent to obtain a substrate having a dry film;

[0009] S3: The substrate with the dry film is subjected to photolithography for patterning, and then the unexposed area is 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 wafer, flexible transparent polyparaxylene film, and the like.

[0011] According to a specific embodiment of the present invention, preferably, the preparation method further comprises before step S1: S0: pre-treating the substrate, wherein the pre-treatment comprises solution pre-treatment or vacuum pre-treatment, and the pre-treatment uses a silane coupling agent. More preferably, the silane coupling agent comprises γ-methacryloxypropyltrimethoxysilane and the like.

[0012] More preferably, in step S0, the solution method pretreatment comprises: immersing the substrate in a pretreatment solution, reacting after immersion, and then drying to obtain a pretreated substrate; the pretreatment solution comprises a solution of γ-methacryloxypropyltrimethoxysilane. Specifically, the solution of γ-methacryloxypropyltrimethoxysilane is a water and isopropanol solution of γ-methacryloxypropyltrimethoxysilane, wherein the volume ratio of γ-methacryloxypropyltrimethoxysilane, water and isopropanol is 1: (50-100): (50-100). The ratio of the substrate and the pretreatment solution can be conventionally adjusted by a person 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 allowed to stand in the air for 15 minutes to react. Before drying, it can be rinsed with isopropanol and then blown dry. Before the above-mentioned pretreatment, the substrate can also be cleaned with water and / or ethanol.

[0013] More preferably, in step S0, the vacuum pretreatment comprises: dripping an appropriate amount of γ-methacryloxypropyltrimethoxysilane into an unsealed vessel, placing the vessel together with the substrate in a vacuum sealed environment, and treating at 80-100°C for a suitable time under vacuum to obtain a pretreated substrate. Specifically, the amount of γ-methacryloxypropyltrimethoxysilane dripped into the unsealed vessel can be adjusted by a person skilled in the art according to the area of ​​the substrate, for example, 200-500 μl of γ-methacryloxypropyltrimethoxysilane can be dripped into the unsealed vessel. The vacuum sealed environment can be provided by a vacuum oven. The vacuum degree of the vacuum state can be 10-200 Pa. The treatment time at 80-100°C under vacuum is preferably such that γ-methacryloxypropyltrimethoxysilane volatilizes and grows on the surface of the substrate, for example, it can be 1-3 hours. Before the above-mentioned 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 derivative of a macromolecular polyethylene glycol with two arms, four arms or eight arms whose terminal groups are thiol groups. 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-arm polyethylene glycol thiol. Further preferably, the molecular weight of the four-arm polyethylene glycol thiol is 5000.

[0015] According to a specific embodiment of the present invention, preferably, in step S1, the prepolymer solution No. 1 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 a buffer solution to obtain a second solution with a hydrogen peroxide mass concentration of 1 to 5%; and uniformly mixing the first solution and the second solution in a volume ratio of 3:(1 to 2) to obtain the prepolymer solution No. 1. More preferably, the pH value of the buffer solution is 7.0 to 8.0, more preferably 7.5, and the concentration is 0.001M to 0.1M, more preferably 0.01M. 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, and after the coating is completed, it is allowed to stand for 5 to 15 minutes to allow the reaction to be complete, thereby obtaining the substrate with a thin film. The process of standing to react can be carried out at room temperature.

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

[0018] According to a specific embodiment of the present invention, preferably, in step S2, the diene water-soluble monomer includes a derivative of a small molecule polyethylene glycol with a vinyl end group. More preferably, the molecular weight of the diene water-soluble monomer is 400 to 700. Specifically, the diene water-soluble monomer includes polyethylene glycol diacrylate (PEGDA) and the like. Further preferably, the molecular weight of the polyethylene glycol diacrylate is 400 to 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-methylpropiophenone and lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP), etc. 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylpropiophenone and lithium phenyl-2,4,6-trimethylbenzoylphosphinate can be used to absorb light in the 365nm and 405nm 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 monoolefinic 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). More preferably, the mass ratio of the monoolefinic water-soluble monomer, the diene 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).

[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 method of removing the solvent includes: heating at 30°C to 70°C for 1 to 10 minutes. Specifically, the method of removing the solvent may include: heating at 30°C to 70°C for 5 to 10 minutes; or, first naturally air-drying for 20 to 40 minutes and / or purging with high-purity nitrogen for 1 to 3 minutes, and then heating at 40°C to 70°C for 1 to 5 minutes. After washing, the residual monomers on the surface of the film can be washed away, and then the above-mentioned solvent removal step is performed to remove the residual hydrogen peroxide and reduce the radical migration rate, thereby increasing the 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 may be 50 mM.

[0026] According to a specific embodiment of the present invention, preferably, in step S3, the process of removing the unexposed area with a developer includes: immersing the substrate with the dry film after photolithography in the developer for 5 to 30 minutes to remove the unexposed area. The specific development time may depend on 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-mentioned method for preparing the high-precision patterned hydrogel.

[0028] According to a specific embodiment of the present invention, preferably, the high-precision patterned hydrogel includes an interwoven first heavy polymer network and a second heavy polymer network, wherein the first heavy polymer network includes a polymer network formed of at least a polyethylene glycol thiol derivative, and the second heavy polymer network includes a polymer network formed of at least a monoolefin water-soluble monomer and a diene water-soluble monomer. It should be noted that the interweaving refers to the interpenetration of the first heavy polymer network and the second heavy polymer network.

[0029] According to a specific embodiment of the present invention, preferably, the first heavy polymer network comprises a polymer network formed by reacting a buffer solution containing a polyethylene glycol thiol derivative 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 monoolefin water-soluble monomer, a diene water-soluble monomer, a water-soluble photoinitiator and an inhibitor as prepolymer solution No. 2.

[0031] The third aspect of the present invention provides a flexible electronic device, which comprises the above-mentioned 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] The present invention is to prepare a high-precision patterned hydrogel by micro-nano processing on a substrate after pretreatment, using polyethylene glycol thiol derivatives as the basic polymer skeleton network (i.e., the first polymer network), introducing monomers and photoinitiators that can form a second polymer network by a solution exchange method, and using the reversibility of the cross-linked disulfide bonds that can be broken under the action of a developer to wash away the unexposed part to form a high-precision patterned hydrogel. The high-precision patterned hydrogel of the present invention avoids the low fidelity of traditional photolithography hydrogels and the problem of excessively high monomer and initiator concentrations in some high-precision system photolithography hydrogels. The high-precision patterned hydrogel of the present invention has good biocompatibility, a water absorption of up to 250%, and a loose pore structure that allows drug molecules and ions to pass through, which is conducive to the exchange of molecules and ions in the polymer network and the external environment, and has high ion permeability. The photolithography accuracy of the high-precision patterned hydrogel of the present invention can reach 4μm. At the same time, the exposure pattern of the present invention is relatively clean, and there is less residue in the development area. Moreover, the present invention adopts a traditional planar exposure process and has the advantage of fast photolithography speed. The high-precision patterned hydrogel of the present invention can be applied to flexible electronic devices, especially as an ion channel. For example, the present invention can be used for the adhesive interface layer of an implantable device, such as the electrolyte layer in an electrochemical transistor, which can ensure both the interface contact and the effectiveness of ion exchange. The present invention is expected to be widely used in various types of flexible implantable devices as one of the technologies for preparing customized patterned adhesion layers. In short, the present invention solves the incompatibility of existing patterned hydrogels in terms of loose pore structure, biocompatibility and precision, and can be well matched with the implant system. BRIEF DESCRIPTION OF THE DRAWINGS

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

[0035] Figure 2 The embodiment 1 of the present invention provides Figure 1 Schematic diagram of high-precision patterned hydrogel under scanning electron microscope.

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

[0037] Figure 4It 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 Example 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 Example 2 of the present invention under a light microscope.

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

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

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

[0043] Fig.10 Schematic diagram of the structure of a vertical type electrochemical transistor for ion permeability testing.

[0044] Fig.11 This is the electrical transfer characteristic curve of the electrochemical transistor assembled with the high-precision patterned hydrogel in Example 1 when working in a 0.1 M standard sodium chloride solution.

[0045] Fig.12 This is the porous network structure of the high-precision patterned hydrogel of Example 1 after freeze-drying. DETAILED DESCRIPTION

[0046] In order to have a clearer understanding of the technical features, purposes and beneficial effects of the present invention, the present invention is now described in detail below, but it should not be construed as limiting the scope of implementation of the present invention.

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

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

[0049] It should be understood that the terms "comprises," "comprising" and / or "containing" when used herein specify the presence of stated features, integers, steps, components or combinations thereof, but do not preclude 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 the present 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 each range, the endpoint values ​​of each range and the individual point values, and the individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be regarded as specifically disclosed in the present invention.

[0051] Example 1

[0052] Prepare a pretreatment solution of γ-methacryloxypropyltrimethoxysilane: pure water: isopropanol in a volume ratio of 1:100:100 and let it stand for 2 hours. Soak a glass with a plane size of 2cm×1.5cm in the pretreatment solution. Before soaking, clean the glass with pure water and / or ethanol. Take it out after soaking for 15 minutes, let it stand in the air for 15 minutes to wait for the reaction to complete, rinse it with isopropanol, and then blow it dry with nitrogen to obtain the pretreated substrate and store it. The pretreated substrate needs to be photolithographically completed within 30 hours.

[0053] Prepare the required solution. Dissolve the four-arm polyethylene glycol thiol with a molecular weight of 5000 in a 0.01M (i.e., mol / L) sodium dihydrogen phosphate-disodium hydrogen phosphate buffer solution with a pH value of 7.5, and ultrasonicate for 3 to 5 minutes until it is completely dissolved and completely defoamed, to obtain a first solution with a concentration of 0.1g / ml of four-arm polyethylene glycol thiol. Dilute a 30% aqueous hydrogen peroxide solution with a 0.01M sodium dihydrogen phosphate-disodium hydrogen phosphate buffer solution with a pH value of 7.5 to a 1% hydrogen peroxide buffer solution as the second solution. Mix 0.1g acrylic acid, 0.1g PEGDA (molecular weight of 400 to 700), 0.025g LAP and 0.25mg 4-methylphenol in 9.8g pure water, and ultrasonicate for 10 minutes until all components are completely dissolved and dispersed evenly to obtain a No. 2 prepolymer solution.

[0054] Take 12 μl of the first solution and 8 μl of the second solution, mix them evenly for 1 minute, and obtain prepolymer solution No. 1. Quickly suck out prepolymer solution No. 1 and drop it on the pretreated substrate, and then cover its surface with a layer of hydrophobic PET, making sure there are no bubbles under the PET, and prepolymer solution No. 1 contacts the hydrophobic surface of the PET. Let it stand for 8 minutes to allow the reaction to be complete, uncover the hydrophobic PET, and obtain a substrate with a thin film. The thickness of the obtained film is 66.7 μm.

[0055] The substrate with the thin film is 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 thin film, and then the substrate is taken out, rinsed with pure water to remove residual monomers on the surface, and then blown dry, and then the substrate is heated at 50°C for 5 minutes to remove residual hydrogen peroxide and water to obtain a substrate with a dry film.

[0056] The substrate with the dry film was photolithographically processed under a maskless photolithography machine with a wavelength of 405 nm, and then immersed in a 50 mM tri(2-carboxyethyl)phosphine hydrochloride solution for development for 30 minutes. The substrate was then taken out and the residual developer was washed away with pure water to obtain a high-precision patterned hydrogel.

[0057] The high-precision patterned hydrogel prepared in this example is shown under a light microscope. Figure 1 As shown in the scanning electron microscope Figure 2 As shown; by adjusting the photolithographic pattern, the high-precision patterned hydrogels with different patterns are obtained under a light microscope. Figure 3 and Figure 5 As shown. It can be seen that the photolithography accuracy of the high-precision patterned hydrogel prepared in this embodiment can reach 4μm. The prepared high-precision patterned hydrogel was soaked in water for 2-3 hours to wait for complete water absorption, then placed in liquid nitrogen for half an hour, and then taken out and dried in a freeze dryer for 1 day. The obtained porous network structure is as shown Fig.12 The high-precision patterned hydrogel comprises a first heavy polymer network and a second heavy polymer network interpenetrating each other, wherein the first heavy polymer network comprises a polymer network formed by at least four-arm polyethylene glycol thiol, and the second heavy polymer network comprises a polymer network formed by at least acrylic acid and PEGDA.

[0058] Example 2

[0059] This example is basically the same as Example 1, except that the acrylic acid in the prepolymer solution No. 2 is replaced by N-vinyl pyrrolidone, the amount used remains unchanged, and the rest is the same as Example 1. The high-precision patterned hydrogel prepared in this example is as shown under a light microscope. Figure 6 The photolithography accuracy 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 the embodiment 1, except that the ratio of the first solution to the second solution is changed to 15 μl and 5 μl, and the rest is the same as the embodiment 1. The photolithography accuracy of the high-precision patterned hydrogel prepared in this embodiment can reach 5 μm.

[0062] Comparative Example 1

[0063] 0.2g acrylic acid, 0.02g PEGDA (molecular weight of 400-700), 1g gelatin, 0.04g 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylpropiophenone, 0.0025g 4-methylphenol and 1.8g pure water were mixed and heated at 70°C for 2-3 hours until the gelatin was completely dissolved and evenly dispersed to obtain a prepolymer solution. The prepolymer solution was spin-coated on a silicon wafer at a speed of 3000 rpm, and then covered with a layer of hydrophobic PET to ensure that there were no bubbles under the PET and that the prepolymer solution contacted the hydrophobic surface of the PET. The substrate covered with PET was then exposed to a 365nm mask-type photolithography machine for 20s, and the unreacted area was washed away with pure water to obtain a patterned hydrogel.

[0064] The patterned hydrogel prepared in this comparative example is as follows under a light microscope: Figure 4 As shown in the figure, it can be seen that there are more residues in the channel and the accuracy is low. Figure 4 and Figure 5 By comparison, it can be seen that the high-precision patterned hydrogel of the same pattern prepared in Example 1 has less residue in the channel. In addition, this comparative example changes the polymerization system, and does not use the polyethylene glycol thiol derivative in the example, but uses gelatin, resulting in the prepolymer liquid of this comparative example being unable to become solid after being coated on the substrate surface. Therefore, this comparative example needs to cover the substrate with PET during photolithography. If the PET is uncovered, the prepolymer liquid will aggregate into droplets in a short time due to the large surface tension, and cannot maintain a uniform thickness on the substrate surface.

[0065] Comparative Example 2

[0066] This comparative example is basically the same as Example 1, except that the four-arm polyethylene glycol thiol with a molecular weight of 5000 is replaced with polyethylene glycol with a molecular weight of 5000, and the amount is unchanged. The preparation steps are also the same as Example 1. The results show that the No. 1 prepolymer droplet is dropped on the pretreated substrate and covers the hydrophobic PET, and after standing, it cannot form a solid state.

[0067] Comparative Example 3

[0068] This comparative example is basically the same as Example 1, except that PEGDA is not added to the prepolymer solution No. 2, and the remaining components and amounts are the same as those in Example 1. The preparation steps are also the same as those in Example 1. The results show that no formation can be achieved after photolithography, and no patterned hydrogel can be obtained.

[0069] Comparative Example 4

[0070] This comparative example is basically the same as Example 1, except that LAP is not added to the prepolymer solution No. 2, and the remaining components and amounts are the same as those in Example 1. The preparation steps are also the same as those in Example 1. The results show that no formation can be achieved after photolithography, and no patterned hydrogel can be obtained.

[0071] Comparative Example 5

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

[0073] Test Case

[0074] The patterned hydrogels provided in the above embodiments were tested for biocompatibility, water absorption and ion permeability. Since the above comparative examples either had too low precision of the patterned hydrogels or could not prepare the patterned hydrogels, the biocompatibility, water absorption and ion permeability of these comparative examples were not tested.

[0075] The biocompatibility test method includes: soaking the patterned hydrogel in HT22 (mouse hippocampal neuron) culture medium at 37°C for 24 hours, extracting the extract as the experimental group, and the HT22 culture medium without the extract as the blank control group. HT22 cells were seeded in a 48-well plate and cultured for 24 hours to adhere to the wall. After that, the experimental group was replaced with the extract culture medium, and the blank group was replaced with the culture medium without the extract. They were cultured at 37°C and 5% CO2 for 1, 3, and 7 days, and the CCK-8 method was used to detect cell proliferation. The biocompatibility results of the blank control group and the high-precision patterned hydrogel using Example 1 after 7 days are shown as follows: Figure 7 The cell proliferation results of different concentrations of extracts are shown in Figure 8 As shown, it is demonstrated that the patterned hydrogel of Example 1 has excellent biocompatibility.

[0076] The test method for water absorption includes: testing the thickness of the dry gel before water absorption and the thickness of the wet gel after water absorption by a step profiler, and obtaining the water absorption 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 FIG. Fig. 9 As shown, it can be seen that the water absorption of the hydrogel of Example 1 is 200% to 250%, and the comparison of the transverse and longitudinal deformations shows that the main water absorption direction is the longitudinal direction. The water absorption of the hydrogels of Examples 2 and 3 is 200 to 250%, which also has a high water absorption. From the water absorption results, it can be verified that the hydrogels of each example have a loose pore structure that allows drug molecules and ions to pass through.

[0077] The test method for ion permeability includes: assembling Fig.10A vertical electrochemical transistor of the structure shown is prepared and tested to see whether it can work properly to determine the ion permeability of the patterned hydrogel. The vertical electrochemical transistor includes a drain circuit, an organic semiconductor, a source circuit, a patterned hydrogel (i.e., a photolithographic hydrogel), a polyparaxylene film, a standard sodium chloride solution, and a gate. Fig.11 The electrical transfer characteristic curve of the electrochemical transistor assembled with the high-precision patterned hydrogel of Example 1 when working in a 0.1M standard sodium chloride solution shows that the hydrogel of Example 1 has good ion permeability, thereby being able to provide 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: using a buffer solution containing a polyethylene glycol thiol derivative and hydrogen peroxide as a No. 1 prepolymerization solution, applying the No. 1 prepolymerization solution to the surface of a substrate, and obtaining a substrate having a thin film after reaction; S2: using an aqueous solution containing a monoolefin water-soluble monomer, a diene water-soluble monomer, a water-soluble photoinitiator and an inhibitor as a No. 2 prepolymerization solution, immersing the substrate having the first thin film in the No. 2 prepolymerization solution, and after immersion, washing and removing the solvent to obtain a substrate having a dry film; S3: The substrate with the dry film is subjected to photolithography for patterning, and then the unexposed area is removed with a developer to obtain the high-precision patterned hydrogel.

2. The method for preparing a high-precision patterned hydrogel according to claim 1, wherein: The substrate comprises one or more of glass, silicon wafer and flexible transparent polyparaxylene film.

3. The method for preparing a high-precision patterned hydrogel according to claim 1, wherein: The preparation method further comprises, before step S1: S0: pre-treating the substrate, wherein the pre-treating comprises solution pre-treating or vacuum pre-treating, and the pre-treating uses a silane coupling agent; Preferably, the silane coupling agent includes γ-methacryloxypropyltrimethoxysilane.

4. The method for preparing a 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 arms, four arms or eight arms and a thiol terminal group; Preferably, the molecular weight of the polyethylene glycol thiol derivative is 1000 to 10000; More preferably, the polyethylene glycol thiol derivative comprises four-arm polyethylene glycol thiol.

5. The method for preparing a high-precision patterned hydrogel according to claim 1, wherein: In step S1, the prepolymer solution No. 1 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 a 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 in a volume ratio of 3:(1 to 2) to obtain the prepolymer solution No. 1; Preferably, the pH value of the buffer solution is 7.0-8.0, and the concentration is 0.001M-0.1M.

6. The method for preparing a high-precision patterned hydrogel according to claim 1, wherein: In step S2, the monoolefinic water-soluble monomer includes one or more of acrylic acid, acrylamide, vinyl pyrrolidone and ethyl methacrylate.

7. The method for preparing a high-precision patterned hydrogel according to claim 1, wherein: In step S2, the diene water-soluble monomer includes a derivative of a small molecule polyethylene glycol having a vinyl terminal group; Preferably, the molecular weight of the diene water-soluble monomer is 400 to 700; More preferably, the diene water-soluble monomer includes polyethylene glycol diacrylate.

8. The method for preparing a 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-methylpropiophenone and lithium phenyl-2,4,6-trimethylbenzoylphosphinate.

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

10. The method for preparing a high-precision patterned hydrogel according to claim 1, wherein: In step S2, the mass ratio of the monoolefin 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); Preferably, the mass ratio of the monoolefin water-soluble monomer, the diene water-soluble monomer, the water-soluble photoinitiator, the inhibitor and water in the No. 2 prepolymer solution is 1: (0.1-1): (0.2-0.5): (0.002-0.005): (10-100).

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

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

13. A high-precision patterned hydrogel, which is prepared by the method for preparing a high-precision patterned hydrogel according to any one of claims 1 to 12.

14. A flexible electronic device comprising the high-precision patterned hydrogel according to claim 13; Preferably, in the flexible electronic device, the high-precision patterned hydrogel serves as an ion channel.

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