Micron-sized hydrogel microarray and method for preparing the same

Abstract

The application discloses a microscale hydrogel microarray and a preparation method thereof. The preparation method comprises the following steps: coating a hydrogel precursor solution on a microarray substrate to obtain a preform; performing a first treatment on the preform to make the hydrogel precursor solution form a hydrogel, and then performing a first vacuum drying to obtain a formed body; and performing a hydration and annealing treatment on the formed body to obtain the microscale hydrogel microarray. By means of the hydration and annealing treatment, the interfacial bonding force between the hydrogel and the substrate can be reduced, so that the preparation of the regular and complete microscale hydrogel microarray is realized. The preparation method has the characteristics of simplicity, high repeatability and strong operability.

Description

Technical Field

[0001] The present invention relates to the technical field of material preparation, and in particular to a micron-scale hydrogel microarray and a preparation method thereof. Background Art

[0002] Hydrogels are cross-linked polymers that can absorb and retain large amounts of water. They possess high hydration properties and a three-dimensional microstructure similar to natural tissue, making them ideal materials for applications in energy, bioelectronics, and biomedicine. They are widely used in the fabrication of supercapacitors, biosensors, and medical electrodes. The design and fabrication of microarrays with hydrogel surface patterns are essential for realizing these functional applications. For example, Professor Ryan Donnelly has invented a hydrogel microneedle patch that can be applied to the skin for transdermal delivery of esketamine, promising treatments for conditions such as major depressive disorder, bipolar depression, and post-traumatic stress disorder.

[0003] To date, many methods for preparing hydrogel microarrays have been reported. Among them, the template method is the main method for preparing hydrogel microarrays because it can accurately control the morphology and size of the microarray. However, due to the flexibility and high water content of hydrogels, their fracture energy is often less than 100 J·m -2 Therefore, the current size of microarrays that can be prepared using template methods is mostly around a few hundred micrometers to a few millimeters. When the size of hydrogel microarrays is gradually reduced to the micron level, the binding force between the hydrogel and the substrate will be much greater than its fracture energy, making it difficult to obtain a regular and complete hydrogel microarray. Summary of the Invention

[0004] The present invention aims to overcome the problem that it is difficult to obtain a regular and complete micron-scale hydrogel microarray in the prior art and to provide a micron-scale hydrogel microarray and a preparation method thereof. The present invention enables the preparation of a regular and complete micron-scale hydrogel microarray.

[0005] In order to achieve the above object, the present invention provides a first aspect of a method for preparing a micron-scale hydrogel microarray, the method comprising the following steps:

[0006] coating a hydrogel precursor solution on a microarray substrate to obtain a preform;

[0007] The preform is subjected to a first treatment to form a hydrogel from the hydrogel precursor solution, and then subjected to a first vacuum drying to obtain a formed body;

[0008] The formed body is hydrated and annealed to obtain a micron-scale hydrogel microarray.

[0009] The second aspect of the present invention provides a micron-scale hydrogel microarray prepared by the aforementioned preparation method.

[0010] Through the above technical solution, the beneficial technical effects achieved by the present invention are as follows:

[0011] The present invention reduces the interfacial bonding force between the hydrogel and the substrate through hydration and annealing treatment, thereby achieving the preparation of regular and complete micron-scale hydrogel microarrays. The preparation method of the present invention has the characteristics of simplicity, high repeatability and strong operability. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] Figure 1 The micron-sized polyaniline conductive hydrogel microarray prepared in Example 1;

[0013] Figure 2 The micron-sized polypyrrole conductive hydrogel microarray prepared in Example 2;

[0014] Figure 3 The micron-sized polyaniline conductive hydrogel microarray prepared in Example 3;

[0015] Figure 4 The micron-sized polyaniline conductive hydrogel microarray prepared in Example 4;

[0016] Figure 5 This is the micron-scale polyaniline conductive hydrogel microarray prepared in Comparative Example 1. DETAILED DESCRIPTION

[0017] The endpoints of the ranges and any values ​​disclosed herein 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 endpoints of each range, the endpoints of each range and 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 considered to be specifically disclosed herein.

[0018] A first aspect of the present invention provides a method for preparing a micron-scale hydrogel microarray, the method comprising the following steps:

[0019] coating a hydrogel precursor solution on a microarray substrate to obtain a preform;

[0020] The preform is subjected to a first treatment to form a hydrogel from the hydrogel precursor solution, and then subjected to a first vacuum drying to obtain a formed body;

[0021] The formed body is hydrated and annealed to obtain a micron-scale hydrogel microarray.

[0022] After in-depth research on hydrogels, the inventors discovered the mechanism by which hydration and annealing treatments affect the stress between the hydrogel and the substrate of a microarray. By exploring and optimizing process parameters, they achieved the design and fabrication of micron-scale hydrogel microarrays using a template method, and proposed a simple technique for fabricating micron-scale conductive hydrogel microarrays. By employing hydration and annealing treatments, the present invention reduces the interfacial bonding between the hydrogel and the substrate, thereby enabling the fabrication of regular, complete micron-scale hydrogel microarrays.

[0023] The preparation method of the present invention has the characteristics of simplicity, high repeatability and strong operability.

[0024] In some embodiments of the present invention, the hydration and annealing steps include: heating the formed body at 60-100°C for 4-6 hours, then cooling it to room temperature, and adding water during the cooling process to complete an annealing process; repeating the annealing process until the hydrogel microarray falls off.

[0025] Specifically, the molded body is placed in an oven at 80° C. and heated for 5 hours, then cooled to room temperature, and a small amount of water is added dropwise to the molded body during the cooling process. The same annealing operation is repeated several times.

[0026] Preferably, 10-20 drops of water are added to the shaped body, and the weight of the added water does not exceed 5 wt % of the weight of the shaped body.

[0027] Repeat the above method several times until the hydrogel microarray automatically falls off, and a regular and complete hydrogel microarray can be obtained. The present invention reduces the binding force between the hydrogel microarray and the silicon wafer substrate through hydration and annealing treatment.

[0028] In some embodiments of the present invention, the first treatment step includes: vacuum drying the preform, and then immersing it in a saturated NaCl solution, changing the water every 4-6 hours.

[0029] The present invention can remove monomers (small molecule cross-linking agent, PVA) that do not participate in the polymerization reaction and some oligomer impurities generated by the polymerization reaction through the first treatment.

[0030] In some preferred embodiments of the present invention, the vacuum drying temperature is 20-30° C. and the time is 4-8 hours.

[0031] In some preferred embodiments of the present invention, the soaking temperature is 15-35° C. and the soaking time is 20-28 h.

[0032] In some embodiments of the present application, the preparation method of the hydrogel precursor solution comprises: preparing a polyvinyl alcohol hydrogel, adding a small molecule crosslinking agent solution, deionized water and a first solution into the polyvinyl alcohol hydrogel respectively to obtain a mixed solution; wherein the first solution is an aniline solution or a pyrrole solution.

[0033] In an ice water bath, the mixed solution is mixed with an ammonium persulfate solution, and after ultrasonic degassing, a conductive hydrogel precursor solution is obtained.

[0034] In some embodiments of the present application, the preparation method of the polyvinyl alcohol hydrogel comprises: mixing polyvinyl alcohol with water to swell, and then stirring and dissolving to obtain a polyvinyl alcohol solution; and then subjecting the polyvinyl alcohol solution to freeze-thaw cycles to obtain a polyvinyl alcohol hydrogel.

[0035] In some preferred embodiments of the present application, the temperature for swelling is 40-80℃, preferably 60℃, until the swelling is completed.

[0036] In some preferred embodiments of the present application, the temperature for stirring and dissolving is 70-100℃, preferably 90℃, and the time is 1-3h, preferably 2h.

[0037] In some preferred embodiments of the present application, the freeze-thaw cycle process comprises: storing the polyvinyl alcohol solution at-10℃ to-30℃ for 14-18h, preferably at-20℃ for 16h, taking it out, thawing at room temperature for 6-10h, preferably 8h, and repeating the storing and thawing for 3-5 times.

[0038] In some embodiments of the present application, the ultrasonic degassing conditions comprise: treating at a temperature of 15-35℃ and an ultrasonic power of 80-120W for 10-30min.

[0039] In some embodiments of the present application, the small molecule crosslinking agent is selected from m-aminobenzoic acid or phytic acid.

[0040] In some preferred embodiments of the present application, the volume ratio of the mixed solution to the ammonium persulfate solution is 1-3:1.

[0041] In some embodiments of the present application, the first vacuum drying temperature is 60-80℃, preferably 70℃, and the time is 1-3h, preferably 2h.

[0042] In some embodiments of the present application, the microarray substrate has a microarray of microns.

[0043] The microarray substrate of the present application is selected according to actual needs.

[0044] In some embodiments of the present invention, the micrometer-scale microarray is a pyramidal microarray, a cubic microarray, a strip microarray, a prism microarray, or a cylindrical microarray.

[0045] In some preferred embodiments of the present invention, in the pyramid-shaped microarray, the base side length of each pyramid is 5-10 μm, the height is 3.5-7.5 μm, and the gap between any two adjacent pyramids is 5-50 μm, for example, 5 μm, 10 μm, 20 μm, 30 μm, 40 μm or 50 μm.

[0046] The second aspect of the present invention provides a micron-scale hydrogel microarray prepared by the aforementioned preparation method.

[0047] In some embodiments of the present invention, the integrity of the micron-scale hydrogel microarray is greater than 90%.

[0048] In the present invention, the integrity of the hydrogel microarray is calculated as follows: (total number - damaged number) / total number * 100%, where the total number refers to the number of all patterns in the microarray, and the damaged number refers to the number of damaged patterns in the microarray.

[0049] The present invention is described in detail below through examples, but the protection scope of the present invention is not limited to the following description.

[0050] In the following examples and comparative examples, if no specific conditions are specified, the experiments were carried out under conventional conditions or those recommended by the manufacturer. All reagents and instruments used were commercially available conventional products.

[0051] Example 1

[0052] The preparation method of micron-scale pyramid-shaped polyaniline conductive hydrogel microarray comprises the following steps:

[0053] (1) Preparation of microarray silicon wafer substrate:

[0054] Pyramid-shaped microarrays with a line width of 5 μm, a height of 3.5 μm, and a gap of 5 μm were fabricated on a 4-inch silicon wafer using photoelectrochemical etching. The microarray silicon wafer substrate was roughly cleaned and then plasma cleaned for 10 minutes. Then, ultrasonically cleaned in acetone, ethanol, and deionized water for 30 minutes each, followed by drying.

[0055] (2) Preparation of conductive hydrogel precursor solution:

[0056] Weigh a certain amount of PVA powder and dissolve it in deionized water to prepare a PVA solution. The PVA solution was first fully swollen at 60°C, then stirred continuously at 90°C for 2 hours. The PVA solution was then cooled to room temperature and set aside. The PVA solution was then stored at -20°C for 16 hours and thawed at room temperature for 8 hours. After completing 3-5 freeze-thaw cycles, the PVA hydrogel was obtained.

[0057] 456.4 mg of ammonium persulfate was weighed and ultrasonically dissolved in 1 mL of deionized water to prepare solution A, and the solution was placed in a 0°C ice-water bath for later use; 18.3 mg of m-aminophenylboronic acid was weighed and added to 835 μL of 6M HCl and ultrasonically dissolved, and then the prepared m-aminophenylboronic acid solution, 225 μL of deionized water and 137.5 μL of aniline solution were slowly added dropwise to 2 mL of 8% PVA gel, stirred evenly to obtain solution B, and placed in a 0°C ice-water bath for later use; in a 0°C ice-water bath, solution A was slowly added dropwise to solution B and stirred rapidly to obtain solution B. After ultrasonically removing bubbles from the mixture, a polyaniline hydrogel precursor solution was obtained.

[0058] (3) Preparation of hydrogel microarray:

[0059] The synthesized hydrogel precursor (a mixed solution of A and B) was evenly spread onto a silicon wafer microarray using a gel spreader. The hydrogel precursor was allowed to stand in a vacuum drying oven at room temperature for 6 hours, whereupon polymerization occurred to produce the corresponding conductive hydrogel. After polymerization, the resulting hydrogel was immersed in a saturated NaCl solution for 24 hours. The water was changed every 8 hours to remove monomers (small molecule crosslinkers, PVA) that did not participate in the polymerization reaction, as well as some oligomeric impurities generated by the polymerization reaction.

[0060] Place the silicon wafer substrate loaded with hydrogel in a vacuum drying oven at 70℃ for 2 hours, and continuously hydrate and anneal to reduce the binding force between the hydrogel microarray and the silicon wafer substrate. Repeat the above method several times until the hydrogel microarray automatically falls off, and you can get Figure 1 The regular and complete hydrogel microarray shown in FIG. 3 is shown. The integrity of the hydrogel microarray is 98% as determined by testing.

[0061] Example 2

[0062] The preparation method of micron-scale pyramid-shaped polypyrrole conductive hydrogel microarray comprises the following steps:

[0063] (1) Preparation of microarray silicon wafer substrate:

[0064] The 4-inch silicon wafer was first cleaned by photoelectrochemical etching to form a pyramid-shaped microarray with a line width of 10 μm, a height of 7.5 μm and a gap of 10 μm. The silicon wafer was then cleaned by plasma for 10 min. The silicon wafer was then sequentially cleaned by ultrasonic cleaning in acetone, ethanol and deionized water for 30 min each, and then dried.

[0065] (2) Preparation of the precursor solution of the conductive hydrogel:

[0066] A certain amount of PVA powder was dissolved in deionized water to prepare a PVA solution. The PVA solution was first swelled at 60°C, and then continuously stirred at 90°C for 2 h. The PVA solution was then cooled to room temperature and stored at -20°C for 16 h, and then thawed at room temperature for 8 h. After 3-5 freeze-thaw cycles, the PVA hydrogel was obtained.

[0067] A solution A was prepared by dissolving 184 mg of ammonium persulfate in 1 mL of deionized water, and then stored in an ice water bath at 0°C. A solution B was prepared by mixing 184 μL of PA solution, 148 μL of pyrrole monomer (the molar ratio of Py / PA was about 6) and 1 mL of isopropyl alcohol, and then slowly added to 2 mL of 8 wt% PVA gel. The mixture was stirred and then placed in an ice water bath at 0°C. Solution A was slowly added to solution B under stirring, and then ultrasonically treated to remove the bubbles. The precursor solution of the conductive hydrogel was obtained.

[0068] (3) Preparation of the hydrogel microarray:

[0069] The precursor solution of the conductive hydrogel was uniformly spread on the silicon wafer microarray by using a spin coater. The precursor solution was placed in a vacuum drying oven at room temperature for 6 h, and then the polymerization reaction was carried out to obtain the corresponding conductive hydrogel. After the polymerization was completed, the obtained hydrogel was soaked in a saturated NaCl solution for 24 h. The water was changed every 8 h to remove the monomers (small molecule crosslinking agent, PVA) and some oligomer impurities generated in the polymerization reaction.

[0070] The silicon wafer substrate loaded with the hydrogel was placed in a vacuum drying oven at 60°C for 2 h to reduce the binding force between the hydrogel microarray and the silicon wafer substrate by hydration and annealing. The above process was repeated several times until the hydrogel microarray was automatically detached, and then a regular and complete hydrogel microarray was obtained as shown in FIG. 2. Figure 2

[0071] Example 3

[0072] The method for preparing the micrometer-level cubic polyaniline conductive hydrogel microarray comprises the following steps: ​

[0073] (1) Preparation of microarray silicon chip substrate:

[0074] Cubic microarrays with 5 μm side length and 5 μm gap were fabricated on 4-inch silicon wafer by photoelectrochemical etching. The microarray silicon chip substrate was cleaned by plasma for 10 min, and then ultrasonically cleaned in acetone, ethanol and deionized water for 30 min, respectively. After drying, the substrate was ready for use.

[0075] (2) Preparation of conductive hydrogel precursor solution:

[0076] A certain amount of PVA powder was dissolved in deionized water to prepare a PVA solution. The PVA solution was first swelled at 60°C, and then continuously stirred at 90°C for 2 h. After cooling to room temperature, the PVA solution was stored at -20°C for 16 h, and then thawed at room temperature for 8 h. After 3-5 freeze-thaw cycles, the PVA hydrogel was obtained.

[0077] 456.4 mg of ammonium persulfate was ultrasonically dissolved in 1 mL of deionized water to prepare solution A, which was stored in an ice water bath at 0°C. 18.3 mg of m-aminobenzoic acid was dissolved in 835 μL of 6M HCl by ultrasonication. Then, 225 μL of deionized water and 137.5 μL of aniline solution were slowly added to 2 mL of 8% PVA gel, respectively, to obtain solution B, which was stored in an ice water bath at 0°C. Solution A was slowly added to solution B under the condition of an ice water bath at 0°C, and then stirred rapidly. After removing the bubbles in the mixed solution by ultrasonication, the polyaniline hydrogel precursor solution was obtained.

[0078] (3) Preparation of hydrogel microarray:

[0079] The synthesized hydrogel precursor solution (the mixed solution of A and B) was uniformly spread on the silicon microarray by using a spin coater. After being placed in a vacuum drying oven at room temperature for 6 h, the hydrogel precursor solution was polymerized to obtain the corresponding conductive hydrogel. After the polymerization was completed, the obtained hydrogel was soaked in a saturated NaCl solution for 24 h. The water was changed every 8 h to remove the monomers (small molecule crosslinking agent, PVA) that did not participate in the polymerization reaction and some oligomer impurities generated in the polymerization reaction.

[0080] The silicon chip substrate loaded with the hydrogel was placed in a vacuum drying oven at 70°C for 2 h to reduce the binding force between the hydrogel microarray and the silicon chip substrate through continuous hydration and annealing treatment. The above process was repeated several times until the hydrogel microarray was automatically detached, and a regular and complete hydrogel microarray as shown in FIG. 4 was obtained. The integrity of the hydrogel microarray was 92% after detection. Figure 3

[0081] Example 4​

[0082] The preparation method of the micrometer-scale prismatic polyaniline conductive hydrogel microarray comprises the following steps:

[0083] (4) Preparation of the microarray silicon wafer substrate:

[0084] A prismatic microarray with a line width of 5 μm and a gap of 10 μm is manufactured on a 4-inch silicon wafer by using a photoelectrochemical etching technology. After the microarray silicon wafer substrate is coarsely washed, it is cleaned by plasma for 10 min, and then is ultrasonically cleaned in acetone, ethanol and deionized water for 30 min each time and dried for standby use.

[0085] (5) Preparation of the conductive hydrogel precursor solution:

[0086] A certain amount of PVA powder is weighed and dissolved in deionized water to prepare a PVA solution; the PVA solution is first fully swollen at 60°C, and is continuously stirred at 90°C for 2 h; the PVA solution is cooled to room temperature and stored at -20°C for 16 h, and is thawed at room temperature for 8 h; after 3-5 freeze-thaw cycles, the PVA hydrogel is obtained.

[0087] 456.4 mg of ammonium persulfate is weighed and ultrasonically dissolved in 1 mL of deionized water to prepare solution A, which is stored in a 0°C ice water bath for standby use; 18.3 mg of m-aminobenzoic acid is weighed and added to 835 μL of 6M HCl, and is ultrasonically dissolved; then 225 μL of deionized water and 137.5 μL of aniline solution are slowly added to 2 mL of 8% PVA gel, respectively, to obtain solution B, which is stored in a 0°C ice water bath for standby use; under the condition of a 0°C ice water bath, solution A is slowly added to solution B, and is quickly stirred uniformly; after ultrasonic removal of bubbles in the mixed solution, the polyaniline hydrogel precursor solution is obtained.

[0088] (6) Preparation of the hydrogel microarray:

[0089] The synthesized hydrogel precursor solution (the mixed solution of A and B) is uniformly spread on the silicon microarray by using a spin coater. After the hydrogel precursor solution is left to stand at room temperature in a vacuum drying oven for 6 h, a corresponding conductive hydrogel is obtained by polymerization. After the polymerization is completed, the obtained hydrogel is soaked in a saturated NaCl solution for 24 h. The water is changed every 8 h to remove monomers (small molecule crosslinking agents, PVA) and some oligomer impurities generated in the polymerization reaction.

[0090] The silicon substrate loaded with the hydrogel is placed in a vacuum drying oven at 70°C for 2 h to reduce the binding force between the hydrogel microarray and the silicon substrate by continuous hydration and annealing treatment. The above method is repeated for several times until the hydrogel microarray automatically falls off, and then a hydrogel microarray as shown in FIG. 1 is obtained. Figure 4The regular and complete hydrogel microarray shown in FIG. 3 is shown. The integrity of the hydrogel microarray was 91% after testing.

[0091] Comparative Example 1

[0092] The micron-scale pyramid-shaped polyaniline conductive hydrogel microarray was prepared according to the method of Example 1, except that the hydrogel microarray was directly peeled off without hydration and annealing treatment to obtain the following: Figure 5 The hydrogel microarray shown in FIG. 3 was tested to determine the integrity of the hydrogel microarray to be 56%.

[0093] The results of Examples 1 and 2 show that the method of the present invention can be used not only for preparing polyaniline hydrogel microarrays but also for preparing polypyrrole hydrogel microarrays, indicating that the method has good applicability.

[0094] It can be seen from the results of Examples 1, 3 and 4 that the method of the present invention can be used to prepare micron-scale hydrogel microarrays of different shapes.

[0095] The results of Example 1 and Comparative Example 1 demonstrate that due to the strong bonding between the hydrogel microarray and the silicon wafer substrate, direct peeling without annealing cannot yield a regular, complete hydrogel microarray. Therefore, annealing can effectively reduce the bonding between the hydrogel and the silicon wafer substrate, resulting in a regular, complete morphology for the hydrogel microarray peeled after annealing.

[0096] The preferred embodiments of the present invention have been described in detail above, but the present invention is not limited thereto. Within the technical concept of the present invention, various simple variations of the technical solution of the present invention may be made, including combining the various technical features in any other appropriate manner. These simple variations and combinations should also be regarded as disclosed in the present invention and fall within the scope of protection of the present invention.

Claims

1. A method for preparing a micron-scale hydrogel microarray, characterized in that: The preparation method comprises the following steps: coating a hydrogel precursor solution on a microarray substrate to obtain a preform; The preform is subjected to a first treatment to form a hydrogel from the hydrogel precursor solution, and then subjected to a first vacuum drying to obtain a formed body; hydrating and annealing the formed body to obtain a micron-scale hydrogel microarray; The method for preparing the hydrogel precursor solution comprises: preparing a polyvinyl alcohol hydrogel, and adding a small molecule crosslinker solution, deionized water, and a first solution to the polyvinyl alcohol hydrogel to obtain a mixed solution; wherein the first solution is an aniline solution or a pyrrole solution; The mixed solution is mixed with an ammonium persulfate solution in an ice-water bath, and ultrasonically degassed to obtain a conductive hydrogel precursor solution; the small molecule cross-linking agent is selected from m-aminophenylboronic acid or phytic acid; The first treatment step comprises: vacuum drying the preform, and then immersing it in a saturated NaCl solution, changing the water every 4-6 hours; The hydration and annealing steps include: heating the formed body at 60-100° C. for 4-6 hours, then cooling it to room temperature, adding water dropwise during the cooling process to complete an annealing process; and repeating the annealing process until the hydrogel microarray falls off.

2. The preparation method according to claim 1, wherein The vacuum drying temperature in the first treatment step is 20-30°C and the time is 4-8h; And / or, the soaking temperature is 15-35° C. and the soaking time is 20-28 hours.

3. The preparation method according to claim 1, wherein The preparation method of the polyvinyl alcohol hydrogel comprises: mixing polyvinyl alcohol with water to swell, and then stirring to dissolve to obtain a polyvinyl alcohol solution; and then subjecting the polyvinyl alcohol solution to a freeze-thaw cycle to obtain the polyvinyl alcohol hydrogel.

4. The preparation method according to claim 3, wherein The swelling temperature is 40-80°C; And / or, the stirring and dissolving temperature is 70-100° C. and the time is 1-3 hours; And / or, the freeze-thaw cycle process includes: storing the polyvinyl alcohol solution at -10°C to -30°C for 14-18 hours, taking it out, and thawing it at room temperature for 6-10 hours; and performing the storage and thawing cycle 3-5 times.

5. The preparation method according to claim 1, wherein The ultrasonic degassing conditions include: treating at a temperature of 15-35° C. and an ultrasonic condition of 80-120W for 10-30 minutes.

6. The preparation method according to claim 5, wherein The volume ratio of the mixed solution to the ammonium persulfate solution is 1-3:

1.

7. The preparation method according to claim 1, wherein The temperature of the first vacuum drying is 60-80° C., and the time is 1-3 hours.

8. The preparation method according to claim 1, wherein The microarray substrate has a micron-scale microarray.

9. The preparation method according to claim 8, wherein The micrometer-scale microarray is a pyramidal microarray, a cubic microarray, a stripe microarray, a prism microarray or a cylindrical microarray; In the pyramid-shaped microarray, the length of the base side of each pyramid is 5-10 μm, the height is 3.5-7.5 μm, and the gap between any two adjacent pyramids is 5-50 μm.

10. A micron-scale hydrogel microarray prepared by the preparation method according to any one of claims 1 to 9.

11. The micron-scale hydrogel microarray according to claim 10, wherein: The integrity of the micron-scale hydrogel microarray is greater than 90%.

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