WO2020051920A1 - Controlled bidirectional three-dimensional deformation hydrogel thin film, preparation method therefor, and flexible microelectrode array - Google Patents

Abstract

A controlled bidirectional three-dimensional deformation hydrogel thin film, a preparation method therefor, and a flexible microelectrode array. Said hydrogel thin film is formed by crosslinking a carboxyl-containing polymer with a divalent or trivalent cation. The hydrogel thin film forms a cross-linking degree gradient in a thickness direction. Plurality of microchannels arranged in an array are arranged on one surface of said hydrogel thin film, and the hydrogel thin film is curled toward a side having the microchannels to generate forward deformation. Said hydrogel thin film can trigger reverse deformation under stimulation of a monovalent cation, pH value and a chelating agent, and controlled adjustment of the degree of deformation of said hydrogel thin film can be achieved by controlling the concentration of a monovalent cation, the magnitude of pH value and the concentration of a chelating agent.

Description

Controllable two-dimensional three-dimensional deformation hydrogel film, preparation method thereof and flexible micro-electrode array Technical field

The invention relates to the technical field of hydrogel, in particular to a controllable bidirectional three-dimensional deformation hydrogel film, a preparation method thereof and a flexible microelectrode array.

Background technique

The stimulus-response hydrogel is a three-dimensional network structure with water as a dispersion medium. It can produce significant volume swelling or shrinkage changes under the external environment such as temperature, pH, light, and ions. In addition, the hydrogel has a soft and rich texture. The elasticity is very close to the texture of living soft tissue, which makes it widely used in software robots, drug release, tissue engineering and other fields. Stimulus-response hydrogels can be combined with gradient cross-links in the thickness direction or differences in local Young's modulus to achieve regionalized swelling or shrinkage differentially, resulting in diverse deformations such as bending and distortion. Existing reports based on controllable deformation hydrogels are mostly based on the heat-sensitive polymer polyisopropylacrylamide, combining multi-material and photopolymerization technologies to achieve regionalized differences in Young's modulus, and differences in the degree of crosslinking in thickness. Controllable deformation occurs under the synergistic effect of in-plane stress and out-of-plane stress. In addition, on the basis of this, non-contact optical, magnetic, and electrically driven hydrogels can be controlled by combining photothermal materials, magnetic materials, and conductive materials. deformation. However, the poor biocompatibility of the materials used has largely limited the application of hydrogel materials in biomedicine and other fields.

Hydrogels based on natural polymers such as sodium alginate, gelatin, and chitosan are widely used in biomedical research for their excellent biocompatibility. Professor Leonid Ionov of Germany reported on Advanced Materials in 2017 that a hydrogel of sodium alginate and hyaluronic acid was constructed based on 4D printing technology to achieve self-curling of the hydrogel to form a closed tubular structure. Cell culture experiments showed The material has excellent biocompatibility. However, this method fails to process more complex structures and cannot regulate the degree of deformation of the hydrogel material. Therefore, how to construct a hydrogel with high biocompatibility, while achieving a gentle triggering method, constructing a diverse and complex structure, and achieving controllable adjustment of the degree of deformation remain a major challenge in this field.

Summary of the Invention

In view of this, the first aspect of the present invention provides a hydrogel film material with near physiological environment triggering, good biocompatibility, simple preparation process and controllable deformation.

Specifically, in a first aspect, the present invention provides a controllable two-dimensional three-dimensional deformation hydrogel film, the hydrogel film is formed from a carboxyl group-containing polymer through divalent or trivalent cation crosslinking, and the hydrogel The film forms a cross-linking gradient along the thickness direction. One side surface of the hydrogel film is provided with a plurality of microchannels arranged in an orientation, and the hydrogel film is curled toward a side having the microchannel to generate a positive deformation.

The carboxyl-containing polymer includes sodium alginate, gelatin, hyaluronic acid, chitosan, cellulose, carboxymethyl cellulose, carboxymethyl chitin, starch, protein, polymethacrylic acid, polyacrylic acid, Carboxylic acid-terminated poly (N-isopropylacrylamide), poly-L-glutamic acid, polyhistidine, polyaspartic acid, polyethylacrylic acid, polypropylacrylic acid, polyvinylbenzoic acid, polycoating Conic acid, peptidoglycan, glutathione, diglycine, elastin-like polypeptide, carboxylated polyvinyl alcohol, carboxylated polypropylene glycol, carboxylated polyethylene glycol, poly (4-carboxybenzenesulfonamide), poly [(R) -3-hydroxybutyric acid], polysebacic acid, polymaleic anhydride, poly-DL-alanine, poly-DL-lysine, poly-DL-ornithine, poly-L- Arginine, poly-L-proline, polyglycolic acid, polyglycine, poly (1,3-propenyl adipate), poly (1,3-propenylglutaric acid), poly (1,3-propene Succinic acid), polyepoxysuccinic acid, other carboxyl-containing polymers, and derivatives and copolymers containing the above units.

In the present invention, the thickness of the hydrogel film is 1 μm to 5 cm, and further, the thickness is 50 μm to 1 mm.

In the present invention, the microchannel is a groove structure, and the microchannels are evenly arranged on one surface of the hydrogel film. The width of the microchannel is 10nm-5cm, and the microchannel is relatively The depth of the side surface is 10 nm-4.5 cm. Further, the width of the microchannel is 1 μm to 5mm, and the depth of the microchannel is 1 μm to 5mm; further, the width is 2 μm to 900 μm, 1 mm to 5 mm, the depth is 2 μm to 900 μm, and 1 mm to 5 mm. The width of the microchannel refers to the width of the opening of the microchannel on the side surface. In the present invention, the specific cross-sectional shape of the microchannel is not particularly limited, and may be any regular or irregular shape, such as a square, a triangle, a semicircle, and the like. The presence of the microchannels makes the thickness of different regions of the hydrogel film different, thereby bringing about a different flexural modulus.

In the present invention, the formation of a cross-linking degree gradient in the hydrogel film along the thickness direction is specifically: the cross-linking degree of the hydrogel film gradually increases from one surface with the microchannel to the opposite surface. The gradient of the cross-linking degree makes the hydrogel film form a difference in Young's modulus in the thickness direction, and the difference is in the range of 0.0001Pa-2000Gpa. Further, the degree of difference is between 10 KPa and 100 MPa.

In the present invention, the divalent cations are Ca ²⁺ , Mg ²⁺ , Ba ²⁺ , Cu ²⁺ , Be ²⁺ , Sr ²⁺ , Ra ²⁺ , Fe ²⁺ , Co ²⁺ , Ni ²⁺ , One or more of Zn ²⁺ , Hg ²⁺ , Cr ²⁺ , Cd ²⁺ , Pd ²⁺ , Pt ²⁺ , Sn ²⁺ , Pb ²⁺ , Mn ²⁺ . Further, the divalent cations are Ca ²⁺ , Mg ²⁺ , Fe ²⁺ , and Zn ²⁺ .

In the present invention, the trivalent cation is one of Fe ³⁺ , Al ³⁺ , Bi ³⁺ , Sc ³⁺ , La ³⁺ , Pr ³⁺ , Gd ³⁺ , Co ³⁺ , Ce ³⁺ or Multiple. Further, the trivalent cations are Fe ³⁺ and Al ³⁺ .

In the present invention, the degree of the positive deformation can be adjusted by controlling the concentration of the divalent or trivalent cation solution and the crosslinking time during the cross-linking process. The concentration of the divalent or trivalent cation solution is 0.1 mmol / L. -10mol / L. Further, the concentration of the divalent or trivalent cation ranges from 10 mmol / L to 1 mol / L.

The hydrogel film provided by the present invention can realize controllable two-dimensional three-dimensional deformation in various ways.

In the present invention, the hydrogel film can be placed in a monovalent cation solution or a mixed solution of a monovalent cation and a divalent or trivalent cation, and the monovalent cation is used to partially replace the cross-linking position of the divalent or trivalent cation. Point, reducing the degree of cross-linking of the system, triggering the swelling of the hydrogel, and the swelling rate of the side of the microchannel with a low degree of cross-linking is greater, thereby triggering the reverse three-dimensional deformation of the hydrogel film; also by adjusting the monovalent cation The concentration of monovalent cations and divalent or trivalent cations in a mixed solution with divalent or trivalent cations can be used to control the ratio of substituted cross-linking sites in a controlled manner by using the competition between the two to achieve the hydrogel film. Precise regulation of mechanical properties to control the deformation of the hydrogel film.

When the hydrogel film is placed in a monovalent cation solution or a mixed solution of a monovalent cation and a divalent or trivalent cation, the hydrogel film is curled toward the side where the microchannel is not provided to generate a reaction. Deformation, further increasing the concentration of the monovalent cation solution can completely dissolve the hydrogel film.

The monovalent cation is one or more of Na ⁺ , K ⁺ , Rb ⁺ , Cs ⁺ , Fr ⁺ , and Ag ⁺ . Further, the monovalent cation is Na ⁺ , K ⁺ . The concentration range of the monovalent cation solution that causes reverse deformation of the hydrogel film is 0.1 mmol / L-10 mol / L; further, the concentration range is 1 mmol / L-1 mol / L. The concentration of the monovalent cation solution that completely dissolves the hydrogel is in the range of 0.25 mol / L-10 mol / L, and further in the range of 5 mol / L-10 mol / L.

In the present invention, for a mixed solution of monovalent cations and divalent or trivalent cations with different volume fractions of a certain concentration, when the volume fraction of monovalent cations is zero, the hydrogel film exhibits a tight microchannel facing inward. The positively deformed three-dimensional structure, when the volume fraction of monovalent cations gradually increases, the substituted cross-linking sites gradually increase, the tight three-dimensional structure will gradually open and even form a two-dimensional flat structure, and further increase the monovalent cation volume fraction. The swelling ratio further increases, and the hydrogel film will gradually bend in the opposite direction to form a three-dimensional structure with the microchannels outward.

In the present invention, the hydrogel film can realize controllable two-dimensional three-dimensional deformation by adjusting pH, and the pH range is 1-14. Further, the pH is 1-14. For example, the hydrogel film is placed in an aqueous solution of pH = 3. At this time, because the pH of the system is less than the pKa of the carboxyl group, the carboxyl group is protonated, and the molecular segment is shrunk. pH, carboxyl group is deprotonated, the molecular segment stretches, the system swells, the hydrogel material will gradually open and become flat, the pH further increases, and the hydrogel will gradually curl in the opposite direction to form a three-dimensional structure with outward microchannels. When pH> 11 is strongly alkaline, divalent or trivalent cations easily form insoluble substances with hydroxide, and the hydrogel film will gradually disintegrate.

In the present invention, the hydrogel film can achieve a controlled two-dimensional three-dimensional deformation by chelating coordination of a chelating agent with a divalent or trivalent cation, and the chelating agent includes EDTA, citric acid, SO ₄ ^{2- _{, CO 3 2-, HCO 3 -}} , CH 3 COO -, C 2 O 4 2-, MnO 4 - of one or more of the chelating agent is a concentration range 0.1mmol / L-10mol / L . Further, the chelating reagent is EDTA and citric acid, and the concentration range is 1 mmol / L-1 mol / L. When the hydrogel is repeatedly washed with deionized water and placed in a reagent capable of chelating with a divalent or trivalent cation for 24 hours, when the hydrogel film having a stable three-dimensional structure of the present invention is placed in a chelating agent, the chelating agent Coordination part with divalent or trivalent cations will replace the crosslinking sites, reduce the density of the hydrogel network, trigger the swelling of the hydrogel, and the swelling rate on the side of the microchannel with a low degree of crosslinking is greater, thereby triggering the hydrocoagulation The reverse swelling and deformation of the gel forms a reverse three-dimensional structure with the microchannels outward.

The controllable bidirectional three-dimensional deformation hydrogel film provided by the first aspect of the present invention, due to the gradient cross-linking in the thickness direction, the difference in Young's modulus of the upper and lower surfaces, and the difference in film thickness between the surface microchannel region and other regions. In order to differentiate the flexural modulus, the out-of-plane stress and in-plane stress formed by the two synergistically cause the hydrogel film to curl toward the microchannel side to undergo a positive deformation to obtain a stable positive three-dimensional structure; the hydrogel film The reverse three-dimensional structure can be obtained by generating reverse deformation under the stimulation of monovalent cation, pH value and chelating agent, and the hydrogel film can be realized by controlling the concentration of monovalent cation, the size of pH value and the concentration of chelating agent. Controllable adjustment of deformation degree.

Accordingly, in a second aspect, the present invention provides a method for preparing a controllable two-dimensional three-dimensional deformation hydrogel film, including the following steps:

Provide a template with a specific structure;

A carboxyl-containing polymer solution is prepared, the carboxyl-containing polymer solution is poured onto the template, and after standing to form a film, the template is immersed in a divalent or trivalent cation solution to make the The carboxyl-containing polymer film layer is pre-crosslinked, and the divalent or trivalent cations are diffused and crosslinked from top to bottom, so that the carboxyl-containing polymer film layer forms a cross-linking gradient in the thickness direction, and the carboxyl-containing polymer film layer is formed. The polymer film layer is peeled from the surface of the template, and a surface of a side of the carboxyl group-containing polymer film layer near the template forms a plurality of microchannels arranged in an array;

The carboxyl-containing polymer film layer is sheared at different angles along the long axis of the microchannel, and then placed in the divalent or trivalent cation solution for complete cross-linking to obtain a hydrogel film. The adhesive film is curled toward a side having the microchannel to generate a positive deformation, and a stable three-dimensional structure is obtained.

In the preparation method of the present invention, the template with a specific structure includes a substrate and a microstructure corresponding to the structure of the microchannel provided on the substrate, and the microstructure can be obtained by photolithography, Specifically, the substrate may be a silicon wafer. The size of the template is set according to the size of the pre-prepared hydrogel film.

In the preparation method of the present invention, the carboxyl group-containing polymer includes sodium alginate, gelatin, hyaluronic acid, chitosan, cellulose, carboxymethyl cellulose, carboxymethyl chitin, starch, protein, and polymethacrylic acid. , Polyacrylic acid, carboxylic acid-terminated poly (N-isopropylacrylamide), poly-L-glutamic acid, polyhistidine, polyaspartic acid, polyethylacrylic acid, polypropylacrylic acid, polyvinylbenzene Formic acid, polyitaconic acid, peptidoglycan, glutathione, diglycine, elastin-like polypeptide, carboxylated polyvinyl alcohol, carboxylated polypropylene glycol, carboxylated polyethylene glycol, poly (4-carboxybenzenesulfonate) Amide), poly [(R) -3-hydroxybutyric acid], polysebacic acid, polymaleic anhydride, poly-DL-alanine, poly-DL-lysine, poly-DL-ornithine, Poly-L-arginine, poly-L-proline, polyglycolic acid, polyglycine, poly (1,3-propenyl adipate), poly (1,3-propenylglutarate), poly (1 , 3-propylene succinic acid), polyepoxysuccinic acid, other carboxyl-containing polymers, and derivatives and copolymers containing the above units. In the carboxyl-containing polymer solution, the solvent may be water, and the mass concentration of the carboxyl-containing polymer solution is 0.01% -50%.

In the present invention, the standing process can be performed at room temperature, and carboxyl-containing polymer film layers of different thicknesses can be obtained by controlling different standing times. Specifically, the standing time may be 1-6 hours, and more specifically, may be 5 hours. In the present invention, the thickness of the hydrogel film may be specifically 1 μm to 5 cm, and further, the thickness is 50 μm to 1 mm.

In the preparation method of the present invention, the concentration of the divalent or trivalent cation solution is 0.1 mmol / L-10 mol / L. Further, the concentration of the divalent or trivalent cation ranges from 10 mmol / L to 1 mol / L. By controlling the concentration of the divalent or trivalent cation solution, the degree of forward deformation can be adjusted to obtain a stable three-dimensional structure with different degrees of deformation. The divalent cations are Ca ²⁺ , Mg ²⁺ , Ba ²⁺ , Cu ²⁺ , Be ²⁺ , Sr ²⁺ , Ra ²⁺ , Fe ²⁺ , Co ²⁺ , Ni ²⁺ , Zn ²⁺ , One or more of Hg ²⁺ , Cr ²⁺ , Cd ²⁺ , Pd ²⁺ , Pt ²⁺ , Sn ²⁺ , Pb ²⁺ , Mn ²⁺ . Further, the divalent cations are Ca ²⁺ , Mg ²⁺ , Fe ²⁺ , and Zn ²⁺ . The trivalent cation is one or more of Fe ³⁺ , Al ³⁺ , Bi ³⁺ , Sc ³⁺ , La ³⁺ , Pr ³⁺ , Gd ³⁺ , Co ³⁺ , and Ce ³⁺ . Further, the trivalent cations are Fe ³⁺ and Al ³⁺ . The pre-crosslinking time may be determined according to the type of the specific carboxyl-containing polymer, and may be 5-15 minutes, and more specifically, 10 minutes.

The divalent or trivalent cation is diffused and cross-linked from top to bottom, so that the carboxyl group-containing polymer film layer forms a cross-linking degree gradient in the thickness direction. Specifically, the cross-linking degree of the hydrogel film is The microchannel gradually increases from one surface to the opposite surface, and the degree of cross-linking makes the hydrogel film form a difference in Young's modulus in the thickness direction, and the difference is in the range of 0.0001Pa-2000Gpa. Inside. Further, the degree of difference is between 10 KPa and 100 MPa.

In the present invention, the microchannel is a groove structure, and the microchannels are evenly arranged on one surface of the hydrogel film. The width of the microchannel is 10nm-5cm, and the depth of the microchannel is 10nm. -4.5cm. Further, the width of the microchannel is 1 μm to 5mm, and the depth of the microchannel is 1 μm to 5mm; further, the width is 2 μm to 900 μm, 1 mm to 5 mm, the depth is 2 μm to 900 μm, and 1 mm to 5 mm. The width of the microchannel refers to the width of the opening of the microchannel on the side surface. In the present invention, the specific cross-sectional shape of the microchannel is not particularly limited, and may be any regular or irregular shape, such as a square, a triangle, a semicircle, and the like. The presence of the microchannels makes the thickness of different regions of the hydrogel film different, thereby bringing about a different flexural modulus.

In the present invention, according to different three-dimensional structures finally obtained, shearing can be performed at different angles, and the specific angle is not limited. In one embodiment of the present invention, it is 0 °, 45 ° or 45 ° along the long axis of the microchannel, respectively. After shearing at an angle of 90 °, hydrogel films with stable three-dimensional structures of hollow tube, spiral and hollow cylinder were obtained after complete cross-linking. The time for the complete crosslinking may be 24 hours.

The preparation method provided by the present invention is simple, convenient, and low in cost.

According to a third aspect, the present invention also provides a flexible microelectrode array, including a flexible substrate, an electrode structure disposed on one side of the flexible substrate, and a stimulus response layer disposed on any part of the flexible substrate. Materials The controllable bidirectional three-dimensional deformation hydrogel film according to the first aspect of the present invention.

The flexible substrate may be a polyimide substrate, a parylene substrate, or a polydimethylsiloxane substrate.

The thickness of the flexible substrate is from 1 μm to 5 mm, and further from 5 μm to 100 μm.

The thickness of the stimulus-response layer is 1 μm to 5 cm, and further 50 μm to 1 mm.

The stimulus-responsive layer of the present invention can be modified on the flexible substrate by means of surface chemical bonding or physical adhesion.

First, the surface chemical bonding is legal

1) Amination of flexible substrate

Take an ordinary flexible microelectrode array, after treatment with acid and alkali, let a large number of carboxyl groups on the surface, and then activate it with EDC / NHS, and react with ethylenediamine to form a large number of amino groups on the surface.

2) Surface chemical bonding

The hydrogel film provided by the present invention is adhered to any part of the flexible microelectrode array, and the free carboxyl group on the surface of the hydrogel film undergoes an amidation reaction with the amino group on the surface of the flexible substrate to realize chemical bonding.

Second, the physical sticky method

A layer of adhesive is coated on the surface of the ordinary flexible microelectrode array, and the hydrogel film provided by the present invention is adhered to any part of the flexible microelectrode array, so that the two layers are adhered together.

The flexible microelectrode array provided by the invention has stable different three-dimensional structures, and can generate reversed three-dimensional structure by generating reverse deformation under the stimulation of monovalent cations, pH value and chelating reagents, and by controlling the concentration of monovalent cations The pH value and the concentration of the chelating agent can realize the controllable adjustment of the deformation degree, and the stimulus response layer is highly biocompatible, so it has broad application prospects in the fields of biomedicine and other fields.

The advantages of the present invention will be partially explained in the following description, part of which is obvious from the description, or can be learned through the implementation of the embodiments of the present invention.

BRIEF DESCRIPTION OF THE DRAWINGS

1 is a schematic structural diagram of a pre-crosslinked hydrogel sample before shearing in Example 1 of the present invention; 10 in the figure is a microchannel;

FIG. 2 is a deformation diagram of a pre-crosslinked hydrogel sample after shearing along different angles of 0 °, 45 °, and 90 ° in Example 1 of the present invention, which is completely crosslinked in a 0.1 mol / L calcium ion solution system. ; Ruler 0.5cm;

3 is a three-dimensional deformation map of a controllable bidirectional three-dimensional deformation hydrogel film prepared in Example 1 of the present invention in a 0.1 mol / L sodium ion solution system; a scale of 0.5 cm;

4 is a bidirectional controllable three-dimensional deformation map of a controllable bidirectional three-dimensional deformation hydrogel film prepared by shearing at a 45 ° angle in Example 1 of the present invention in a mixed solution of sodium ions and calcium ions with different compositions; scale 1cm ;

FIG. 5 is a deformation diagram of a flexible microelectrode array prepared in Example 12 of the present invention.

detailed description

The following is a preferred implementation of the embodiment of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the principle of the embodiment of the present invention, several improvements and retouching can be made. These improvements He retouching is also considered as the protection scope of the embodiments of the present invention.

Example 1

A controllable bidirectional three-dimensional deformation hydrogel film, the surface of the hydrogel film has directionally arranged microchannels, and a degree of cross-linking gradient in thickness. The hydrogel film is obtained by cross-linking sodium alginate with calcium ions. ; Wherein the depth of the microchannel is 100 μm and the width is 800 μm.

The method for preparing the controllable two-dimensional three-dimensional deformation hydrogel film includes the following steps:

(1) Rinse the silicon wafer with acetone, ethanol, and water in sequence. After purging with nitrogen, place the wafer in a plasma cleaner for 1 minute. The photoresist SU-83050 was spin-coated on the surface of the silicon wafer at a speed of 1200r / min for 30s, and then placed on a 95 ° C hot table for 30s. Finally, a silicon-based template with a specific structure (length and width of 4 cm × 4 cm) is obtained after development processing by photolithography (using a lithography machine model EVG 610 of Austria).

(2) A 5% sodium alginate aqueous solution is prepared, 1 mL is poured onto the silicon-based template obtained above, and it is left to stand at room temperature for 5 hours to form a uniform film layer. Subsequently, it was immersed in a 0.1 mol / L calcium chloride solution for 10 minutes for pre-crosslinking to form, and the gradient cross-linking degree in the thickness direction was formed by calcium ion diffusion cross-linking from top to bottom. The pre-crosslinked film layer was peeled off from the silicon-based template to obtain a sodium alginate film layer with a plurality of microchannels aligned in one direction as shown in FIG. 1. (°, 45 °, 90 °) shearing to obtain a 3.5cm × 0.5cm pre-crosslinked hydrogel sample. Finally, the sample obtained by shearing at 0 °, 45 °, and 90 ° was placed in a 0.1 mol / L chlorinated solution. The calcium solution was completely cross-linked for 24 hours to form hydrogel films with different three-dimensional structures such as hollow tubes, spirals, and cylinders with the microchannels facing inward as shown in FIG. 2.

Stimulus-triggered deformation experiment:

A. The hollow tube, spiral, and cylinder with the microchannels obtained in this example facing inward, and three different three-dimensional structures of the hydrogel film are placed in a 0.1mol / L sodium chloride solution for 24 hours, and the sodium ions will gradually be replaced. Coordinated cross-linked calcium ions reduce the degree of cross-linking of the hydrogel, triggering the swelling deformation of the hydrogel, where the degree of cross-linking is smaller, the swelling rate is greater, thereby forming microchannels outward as shown in Figure 3 Different three-dimensional structures of inverted hollow tube, spiral, and cylinder.

B. The spiral hydrogel film (45 °) with the microchannels facing inward obtained in this example is placed in a mixed solution of sodium ions and calcium ions with different volume fractions at a concentration of 1 mmol / L for 24 hours, using sodium and calcium ions Competition to precisely adjust the mechanical properties of the material, thereby effectively controlling the degree of deformation of the hydrogel film. It can be observed from Fig. 4 that when the volume fraction of sodium ions increases from 0% to 64%, the inward spiral of the microchannel gradually opens to become a flat two-dimensional hydrogel. When the volume fraction of sodium ions further increases, the water The gel will gradually swell in the opposite direction to form a reverse spiral structure with outward channels.

Example 2

A controllable bidirectional three-dimensional deformation hydrogel film, the surface of the hydrogel film has directionally arranged microchannels, and a degree of cross-linking gradient in thickness. The material of the hydrogel film is sodium alginate cross-linked by zinc ions. The microchannels have a depth of 5 μm and a width of 1 μm.

The method for preparing the controllable two-dimensional three-dimensional deformation hydrogel film includes the following steps:

(1) Rinse the silicon wafer with acetone, ethanol, and water in sequence. After purging with nitrogen, place the wafer in a plasma cleaner for 1 minute. The photoresist AZ 5214 was spin-coated on the surface of the silicon wafer at a rotation speed of 3000 r / m for 30 seconds, and then placed on a 95 ° C hot table for 30 seconds. Finally, a silicon-based template with a specific structure (length and width of 4 cm × 4 cm) is obtained after the photolithographic development process.

(2) A 1% sodium alginate aqueous solution is prepared, 0.5 mL is poured onto the silicon-based template obtained above, and it is left to stand at room temperature for 5 hours to form a uniform film layer. Subsequently, it was immersed in a 5mol / L Zn ²⁺ solution for pre-crosslinking for 10 minutes, and then the Zn ²⁺ ions were diffused and crosslinked from top to bottom to form a gradient crosslinking degree in the thickness direction. The pre-crosslinked film layer was peeled off from the silicon-based template to obtain a film layer with a plurality of microchannels aligned on one side surface, and cut along different angles of the microchannel (0 °, 45 °, 90 °). A 3.5 cm × 0.5 cm pre-crosslinked hydrogel sample was cut out. Finally, the obtained sample was completely cross-linked in a 10 mol / L Zn ²⁺ solution for 24 hours to form a hollow tubular, spiral, Hydrogel films with different three-dimensional structures in cylinders.

Stimulus-triggered deformation experiment:

A. The hollow tube, spiral, and cylinder with the microchannels obtained in this example inward, and three different three-dimensional structures of the hydrogel film are placed in a 0.1 mmol / L K ⁺ ion solution for 24 h, and the K ⁺ ions will gradually Replace the coordinated cross-linked Zn ²⁺ ions, reduce the degree of cross-linking of the material, and trigger the swelling deformation of the hydrogel. The swelling rate is greater where the degree of cross-linking is small, forming an inverted hollow tubular, spiral with microchannels outward. Shape, cylinder and other three-dimensional structures.

B. The spiral hydrogel film (45 °) with the microchannels facing inward obtained in this example is placed in a mixed solution of K ⁺ and Zn ^{2+ with} different volume fractions of 0.1 mol / L for 24 h, and K ⁺ and Zn ^{2 are used. +} Ion competition to accurately adjust the mechanical properties of the material, so as to effectively control the degree of deformation of the hydrogel material. When the volume fraction of K ⁺ ions increases from 0% to 98%, the inward spiral of the microchannel gradually opens to become a flat two-dimensional hydrogel. When the volume fraction of K ⁺ ions increases further, the hydrogel will gradually reverse The swelling forms a reverse spiral structure with the channels outward.

Example 3

A controllable bidirectional three-dimensional deformation hydrogel film, the surface of the hydrogel film has directionally arranged microchannels, and a degree of cross-linking gradient in thickness. The material of the hydrogel film is polyacrylic acid cross-linked by iron ions. Obtained; wherein the depth of the microchannel is 1mm and the width is 5mm.

The method for preparing the controllable two-dimensional three-dimensional deformation hydrogel film includes the following steps:

(1) Rinse the silicon wafer with acetone, ethanol, and water in sequence. After purging with nitrogen, place the wafer in a plasma cleaner for 1 minute. Photoresist SU-83050 was applied dropwise to the surface of a clean silicon wafer to form a photoresist layer with a thickness of 1 mm, and then placed on a 95 ° C hot stage for 30 seconds. Finally, a silicon-based template with a specific structure (length and width of 4 cm × 4 cm) is obtained after the photolithographic development process.

(2) A polyacrylic acid aqueous solution having a mass fraction of 5% is prepared, and 5 mL is poured onto the silicon-based template obtained above, and left to stand at room temperature for 5 hours to form a uniform film layer. Subsequently, it was immersed in a 2.5mol / L Fe ³⁺ solution for pre-crosslinking for 10 minutes, and the gradient cross-linking degree in the thickness direction was formed by diffusion cross-linking of iron ions from top to bottom. The pre-crosslinked film layer was peeled off from the silicon-based template to obtain a film layer with a plurality of microchannels aligned on one side surface, and cut along different angles of the microchannel (0 °, 45 °, 90 °). A 3.5 cm × 0.5 cm pre-crosslinked hydrogel sample was cut out. Finally, the obtained sample was completely cross-linked in a 2.5 mol / L Fe ³⁺ solution for 24 hours to form a hollow tubular and spiral shape with the microchannels facing inward. 3. Hydrogel films with different three-dimensional structures in cylinders.

Stimulus-triggered deformation experiment:

A. The hollow tube, spiral, and cylinder with the microchannels obtained in this embodiment facing inward, and three different three-dimensional structures of the hydrogel film are placed in a 0.25mol / L Ag ⁺ solution for 24 hours. Silver ions will gradually replace the compound. Fe ³⁺ ions that are cross-linked reduce the degree of cross-linking of the material and trigger the swelling deformation of the hydrogel. Where the degree of cross-linking is small, the swelling rate is greater, forming an inverted hollow tubular, spiral, Different three-dimensional structures such as cylinders.

B. The spiral hydrogel film (45 °) with the microchannels facing inward obtained in this example is placed in a mixed solution of Ag ⁺ , Fe3 ⁺ ions with different volume fractions of 0.05mol / L for 24h, and Ag ⁺ , Fe are used. ³⁺ ions compete to precisely adjust the mechanical properties of the material, thereby effectively controlling the degree of deformation of the hydrogel material. When the volume fraction of Ag ⁺ ions increases from 0% to 75%, the inward spiral of the microchannel gradually opens into a flat two-dimensional hydrogel. When the volume fraction of Ag ⁺ ions increases further, the hydrogel will gradually reverse The swelling forms a reverse spiral structure with the channels outward.

Example 4

A controllable bidirectional three-dimensional deformation hydrogel film, the surface of the hydrogel film has directionally arranged microchannels, and a degree of cross-linking gradient in thickness. The material of the hydrogel film is chitosan cross-linked by calcium ions. The microchannels have a depth of 10 nm and a width of 10 nm.

The method for preparing the controllable two-dimensional three-dimensional deformation hydrogel film includes the following steps:

(1) Rinse the silicon wafer with acetone, ethanol, and water in sequence. After purging with nitrogen, place the wafer in a plasma cleaner for 1 minute. The photoresist AZ 5214 was spin-coated on the surface of the silicon wafer at a rotation speed of 5000 r / m for 30 seconds, and then placed on a 95 ° C hot table for 30 seconds. Finally, a silicon-based template with a specific structure (length and width of 4 cm × 4 cm) is obtained after the photolithographic development process.

(2) A 3% chitosan solution was prepared from a 3% acetic acid solution by volume, and 1 mL was poured onto the silicon-based template obtained above, and allowed to stand at room temperature for 5 hours to form a uniform film layer. Subsequently, it was immersed in a 10 mol / L calcium chloride solution for pre-crosslinking for 10 minutes to form a gradient cross-linking degree in the thickness direction by calcium ion diffusion cross-linking from top to bottom. The pre-crosslinked film layer was peeled off from the silicon-based template to obtain a film layer with a plurality of microchannels aligned in one direction on one surface, and cut along different angles of the microchannel (0 °, 45 °, 90 °). A 3.5 cm × 0.5 cm pre-crosslinked hydrogel sample was cut out. Finally, the obtained sample was completely cross-linked in a 10 mol / L calcium chloride solution for 24 hours to form a hollow tube, a spiral, Hydrogel films with different three-dimensional structures in cylinders.

Stimulus-triggered deformation experiment:

A. The hollow tube, spiral, and cylinder with the microchannels obtained in this example facing inward, and three different three-dimensional structures of the hydrogel film are placed in a 10mol / L sodium chloride solution for 24 hours, and the sodium ion will completely replace the compound. Cross-linked calcium ions break all cross-linking sites and trigger the disintegration of the hydrogel.

B. The spiral hydrogel film (45 °) with the microchannels facing inward obtained in this example is placed in a sodium-calcium mixed solution with different volume fractions of 1mmol / L for 24h, and the competition of sodium-calcium ions is used to precisely adjust the material. Mechanical properties, so as to effectively control the degree of deformation of the hydrogel material. When the volume fraction of sodium ions increases from 0% to 64%, the inward spiral of the microchannel gradually opens into a flat two-dimensional hydrogel. When the volume fraction of sodium ions increases further, the hydrogel will gradually swell in the opposite direction to form Channel reverse outward spiral structure.

Example 5

A controllable two-dimensional three-dimensional deformation hydrogel film, the surface of the hydrogel film has directionally arranged microchannels, and a degree of cross-linking gradient in thickness. The material of the hydrogel film is gelatin obtained by calcium ion cross-linking. ; Wherein the depth of the microchannel is 4.5cm and the width is 5cm.

The method for preparing the controllable two-dimensional three-dimensional deformation hydrogel film includes the following steps:

(1) Rinse the silicon wafer with acetone, ethanol, and water in sequence. After purging with nitrogen, place the wafer in a plasma cleaner for 1 minute. The photoresist AZ 5214 was applied dropwise to the surface of the silicon wafer, and then placed on a 95 ° C hot stage for 30 seconds. Finally, a silicon-based template with a specific structure (length and width of 4 cm × 4 cm) is obtained after the photolithographic development process.

(2) A gelatin aqueous solution having a mass fraction of 5% is prepared, 1 mL is poured onto the silicon-based template obtained above, and it is left to stand at room temperature for 5 hours to form a uniform film layer. Subsequently, it was immersed in a 5 mol / L calcium chloride solution for 10 minutes for pre-crosslinking to form, and a gradient cross-linking degree in the thickness direction was formed by calcium ion diffusion cross-linking from top to bottom. The pre-crosslinked film layer was peeled off from the silicon-based template to obtain a film layer with a plurality of microchannels aligned on one side surface, and cut along different angles of the microchannel (0 °, 45 °, 90 °). A 3.5 cm × 0.5 cm pre-crosslinked hydrogel sample was cut out. Finally, the obtained sample was completely cross-linked in a 5 mol / L calcium chloride solution for 24 hours to form a hollow tubular, spiral, Hydrogel films with different three-dimensional structures in cylinders.

Stimulus-triggered deformation experiment:

A. The hollow tube, spiral, and cylinder with the microchannels obtained in this example facing inward, and three different three-dimensional structures of the hydrogel film are placed in a 2.5mol / L sodium chloride solution for 24 hours, and the sodium ions will be completely replaced. Coordinated cross-linked calcium ions break all cross-linking sites and trigger the disintegration of the hydrogel.

B. The spiral hydrogel film (45 °) with the microchannels inwardly obtained in this embodiment is placed in a sodium calcium mixed solution with different volume fractions of 0.1 mol / L for 24 hours, and the competition of sodium and calcium ions is used for precise adjustment. The mechanical properties of the material effectively control the degree of deformation of the hydrogel material. When the volume fraction of sodium ions increases from 0% to 98%, the inward spiral of the microchannel gradually opens into a flat two-dimensional hydrogel. When the volume fraction of sodium ions further increases, the hydrogel will gradually swell in the opposite direction to form Channel reverse outward spiral structure.

Example 6

A controllable bidirectional three-dimensional deformation hydrogel film, the surface of the hydrogel film has directionally arranged microchannels, and a degree of cross-linking gradient in thickness. The material of the hydrogel film is hyaluronic acid cross-linked by magnesium ions. The microchannels have a depth of 1mm and a width of 5mm.

The method for preparing the controllable two-dimensional three-dimensional deformation hydrogel film includes the following steps:

(1) Rinse the silicon wafer with acetone, ethanol, and water in sequence. After purging with nitrogen, place the wafer in a plasma cleaner for 1 minute. Photoresist SU-83050 was applied dropwise to the surface of a clean silicon wafer to form a photoresist layer with a thickness of 1 mm, and then placed on a 95 ° C hot stage for 30 seconds. Finally, a silicon-based template with a specific structure (length and width of 4 cm × 4 cm) is obtained after the photolithographic development process.

(2) A 5% hyaluronic acid aqueous solution is prepared, 5 mL is poured onto the silicon-based template obtained above, and it is left to stand at room temperature for 5 hours to form a uniform film layer. Subsequently, it was immersed in a 0.1mmol / L Mg ²⁺ ion solution for pre-crosslinking for 10 minutes, and then the Mg ²⁺ ions were diffused and crosslinked from top to bottom to form a gradient crosslinking degree in the thickness direction. The pre-crosslinked film layer was peeled off from the silicon-based template to obtain a film layer with a plurality of microchannels aligned on one side surface, and cut along different angles of the microchannel (0 °, 45 °, 90 °). A 3.5 cm × 0.5 cm pre-crosslinked hydrogel sample was cut out. Finally, the obtained sample was completely cross-linked in a 0.1 mmol / L Mg ²⁺ ion solution for 24 hours to form a hollow tubular and spiral shape with the microchannels facing inward. 3. Hydrogel films with different three-dimensional structures in cylinders.

Stimulus-triggered deformation experiment:

A. The hollow tube, spiral, and cylinder with the microchannels obtained in this example facing inward, and three different three-dimensional structures of the hydrogel film are placed in a 0.25mol / L K ⁺ solution for 24h, and K ⁺ ions will gradually replace Coordinated and cross-linked calcium ions reduce the degree of material cross-linking of the material and trigger the swelling deformation of the hydrogel. Where the degree of cross-linking is small, the swelling rate is greater, forming an inverted hollow tubular, spiral, Different three-dimensional structures such as cylinders.

B. The spiral hydrogel film (45 °) with the microchannels facing inward obtained in this example is placed in a mixed solution of K ⁺ ions and Mg ²⁺ ions with different volume fractions of 0.05 mol / L for 24 h. Competition to precisely adjust the mechanical properties of the material, thereby effectively controlling the degree of deformation of the hydrogel material. When the volume fraction of sodium ions increases from 0% to 75%, the inward spiral of the microchannel gradually opens into a flat two-dimensional hydrogel. When the volume fraction of sodium ions increases further, the hydrogel will gradually swell in the opposite direction to form Channel reverse outward spiral structure.

Example 7

A controllable bidirectional three-dimensional deformation hydrogel film, the surface of the hydrogel film has directionally arranged microchannels and a cross-linking gradient in thickness. The material of the hydrogel film is a combination of sodium alginate and gelatin. The mixture is obtained by cross-linking of calcium ions; wherein the microchannel has a depth of 100 μm and a width of 800 μm.

The method for preparing the controllable two-dimensional three-dimensional deformation hydrogel film includes the following steps:

(1) Rinse the silicon wafer with acetone, ethanol, and water in sequence. After purging with nitrogen, place the wafer in a plasma cleaner for 1 minute. The photoresist SU-83050 was spin-coated on the surface of the silicon wafer at a speed of 1200r / m for 30s, and then placed on a 95 ° C hot table for 30s. Finally, a silicon-based template with a specific structure (length and width of 4 cm × 4 cm) is obtained after the photolithographic development process.

(2) Formulate a 5% sodium alginate aqueous solution and a 5% gelatin solution, mix the two in a volume ratio of 1: 1, take 1mL and pour onto the silicon-based template obtained above. Set for 5h to form a uniform film layer. Subsequently, it was immersed in a 0.1 mol / L calcium chloride solution for 10 minutes for pre-crosslinking to form, and the gradient cross-linking degree in the thickness direction was formed by calcium ion diffusion cross-linking from top to bottom. The pre-crosslinked film layer was peeled off from the silicon-based template to obtain a film layer with a plurality of microchannels aligned on one side surface, and cut along different angles of the microchannel (0 °, 45 °, 90 °). A 3.5 cm × 0.5 cm pre-crosslinked hydrogel sample was cut out. Finally, the obtained sample was completely cross-linked in a 0.1 mol / L calcium chloride solution for 24 hours to form a hollow tubular and spiral shape with the microchannels facing inwardly. 3. Hydrogel films with different three-dimensional structures in cylinders.

Stimulus-triggered deformation experiment:

A. The hollow tube, spiral, and cylinder with the microchannels obtained in this example facing inward, and three different three-dimensional structures of the hydrogel film are placed in a 0.1mol / L sodium chloride solution for 24 hours, and the sodium ions will gradually be replaced. Coordinated and cross-linked calcium ions reduce the degree of material cross-linking of the material and trigger the swelling deformation of the hydrogel. Where the degree of cross-linking is small, the swelling rate is greater, forming an inverted hollow tubular, spiral, Different three-dimensional structures such as cylinders.

B. The spiral hydrogel film (45 °) with the microchannels facing inward obtained in this example is placed in a sodium-calcium mixed solution with different volume fractions of 1mmol / L for 24h, and the competition of sodium-calcium ions is used to precisely adjust the material. Mechanical properties, so as to effectively control the degree of deformation of the hydrogel material. When the volume fraction of sodium ions increases from 0% to 64%, the inward spiral of the microchannel gradually opens into a flat two-dimensional hydrogel. When the volume fraction of sodium ions increases further, the hydrogel will gradually swell in the opposite direction to form Channel reverse outward spiral structure.

Example 8

A controllable bidirectional three-dimensional deformation hydrogel film, the surface of the hydrogel film has directionally arranged microchannels and a degree of cross-linking gradient in thickness, and the materials of the hydrogel film are sodium alginate and chitosan The blend was obtained by cross-linking of calcium ions; wherein the depth of the microchannel was 5 μm and the width was 1 μm.

The method for preparing the controllable two-dimensional three-dimensional deformation hydrogel film includes the following steps:

(1) Rinse the silicon wafer with acetone, ethanol, and water in sequence. After purging with nitrogen, place the wafer in a plasma cleaner for 1 minute. The photoresist AZ 5214 was spin-coated on the surface of the silicon wafer at a rotation speed of 3000 r / m for 30 seconds, and then placed on a 95 ° C hot table for 30 seconds. Finally, a silicon-based template with a specific structure (length and width of 4 cm × 4 cm) is obtained after the photolithographic development process.

(2) Prepare a 1% sodium alginate aqueous solution, and use a 3% acetic acid as a solvent to configure a 1% chitosan solution. Mix the two at a volume ratio of 1: 1 and take 0.5mL to pour. On the silicon-based template obtained above, it was left to stand at room temperature for 5 hours to form a uniform film layer. Subsequently, it was immersed in a 5 mol / L calcium chloride solution for 10 minutes for pre-crosslinking to form, and a gradient cross-linking degree in the thickness direction was formed by calcium ion diffusion cross-linking from top to bottom. The pre-crosslinked film layer was peeled off from the silicon-based template to obtain a film layer with a plurality of microchannels aligned on one side surface, and cut along different angles of the microchannel (0 °, 45 °, 90 °). A 3.5 cm × 0.5 cm pre-crosslinked hydrogel sample was cut out. Finally, the obtained sample was completely cross-linked in a 5 mol / L calcium chloride solution for 24 hours to form a hollow tubular, spiral, Hydrogel films with different three-dimensional structures in cylinders.

Stimulus-triggered deformation experiment:

A. The hollow tubular, spiral, and cylindrical bodies with three different three-dimensional structures of the microchannels obtained in this example facing inward are placed in a 1 mmol / L sodium chloride solution for 24 hours, and sodium ions will gradually replace the compound. Cross-linked calcium ions reduce the degree of cross-linking of the material and trigger the swelling deformation of the hydrogel. The swelling rate is greater where the degree of cross-linking is small, forming an inverted hollow tubular, spiral, cylindrical column with microchannels outward. Volume and other three-dimensional structures.

B. The spiral hydrogel film (45 °) with the microchannels inwardly obtained in this embodiment is placed in a sodium calcium mixed solution with different volume fractions of 0.1 mol / L for 24 hours, and the competition of sodium and calcium ions is used to precisely adjust The mechanical properties of the material effectively control the degree of deformation of the hydrogel material. When the volume fraction of sodium ions increases from 0% to 98%, the inward spiral of the microchannel gradually opens into a flat two-dimensional hydrogel. When the volume fraction of sodium ions further increases, the hydrogel will gradually swell in the opposite direction to form Channel reverse outward spiral structure.

Example 9

A controllable bidirectional three-dimensional deformation hydrogel film, the surface of the hydrogel film has directionally arranged microchannels, and a degree of cross-linking gradient in thickness. The material of the hydrogel film is sodium alginate and hyaluronic acid. The blend is obtained by cross-linking of calcium ions; wherein the depth of the microchannel is 1mm and the width is 5mm.

The method for preparing the controllable two-dimensional three-dimensional deformation hydrogel film includes the following steps:

(1) Rinse the silicon wafer with acetone, ethanol, and water in sequence. After purging with nitrogen, place the wafer in a plasma cleaner for 1 minute. Photoresist SU-83050 was applied dropwise to the surface of a clean silicon wafer to form a photoresist layer with a thickness of 1 mm, and then placed on a 95 ° C hot stage for 30 seconds. Finally, a silicon-based template with a specific structure (length and width of 4 cm × 4 cm) is obtained after the photolithographic development process.

(2) Prepare a 5% sodium alginate aqueous solution and a 5% hyaluronic acid solution, mix the two at a volume ratio of 1: 1, and pour 5 mL on the silicon-based template obtained above. Let stand for 5h at room temperature to form a uniform film layer. Subsequently, it was immersed in 2.5mol / L calcium chloride solution for 10 minutes for pre-crosslinking to form a gradient cross-linking degree in the thickness direction by calcium ion diffusion cross-linking from top to bottom. The pre-crosslinked film layer was peeled off from the silicon-based template to obtain a film layer with a plurality of microchannels aligned on one side surface, and cut along different angles of the microchannel (0 °, 45 °, 90 °). A 3.5 cm × 0.5 cm pre-crosslinked hydrogel sample was cut out. Finally, the obtained sample was completely cross-linked in a 2.5 mol / L calcium chloride solution for 24 hours to form a hollow tubular and spiral shape with the microchannels facing inwardly. 3. Hydrogel films with different three-dimensional structures in cylinders.

Stimulus-triggered deformation experiment:

A. The hollow tube, spiral, and cylinder with the microchannels obtained in this example facing inward, three different three-dimensional structures of the hydrogel film are placed in a 0.25mol / L sodium chloride solution for 24 hours, and sodium ions will gradually be replaced. Coordinated and cross-linked calcium ions reduce the degree of material cross-linking of the material and trigger the swelling deformation of the hydrogel. Where the degree of cross-linking is small, the swelling rate is greater, forming an inverted hollow tubular, spiral, Different three-dimensional structures such as cylinders.

B. The spiral hydrogel film (45 °) with the microchannels inwardly obtained in this example is placed in a sodium-calcium mixed solution with different volume fractions of 0.05mol / L for 24 hours, and the competitive effect of sodium-calcium ions is used for precise adjustment. The mechanical properties of the material effectively control the degree of deformation of the hydrogel material. When the volume fraction of sodium ions increases from 0% to 75%, the inward spiral of the microchannel gradually opens into a flat two-dimensional hydrogel. When the volume fraction of sodium ions increases further, the hydrogel will gradually swell in the opposite direction to form Channel reverse outward spiral structure.

Example 10

A controllable bidirectional three-dimensional deformation hydrogel film, the surface of the hydrogel film has directionally arranged microchannels and a degree of cross-linking gradient in thickness. The material of the hydrogel film is sodium alginate cross-linked by calcium ions. The microchannels have a depth of 100 μm and a width of 800 μm.

The method for preparing the controllable two-dimensional three-dimensional deformation hydrogel film includes the following steps:

(1) Rinse the silicon wafer with acetone, ethanol, and water in sequence. After purging with nitrogen, place the wafer in a plasma cleaner for 1 minute. The photoresist SU-83050 was spin-coated on the surface of the silicon wafer at a speed of 1200r / m for 30s, and then placed on a 95 ° C hot table for 30s. Finally, a silicon-based template with a specific structure (length and width of 4 cm × 4 cm) is obtained after the photolithographic development process.

(2) A 5% sodium alginate aqueous solution is prepared, 1 mL is poured onto the silicon-based template obtained above, and it is left to stand at room temperature for 5 hours to form a uniform film layer. Subsequently, it was immersed in a 0.1 mol / L calcium chloride solution for 10 minutes for pre-crosslinking to form, and the gradient cross-linking degree in the thickness direction was formed by calcium ion diffusion cross-linking from top to bottom. The pre-crosslinked film layer was peeled off from the silicon-based template to obtain a film layer with a plurality of microchannels aligned on one side surface, and cut along different angles of the microchannel (0 °, 45 °, 90 °). A 3.5 cm × 0.5 cm pre-crosslinked hydrogel sample was cut out. Finally, the obtained sample was completely cross-linked in a 0.1 mol / L calcium chloride solution for 24 hours to form a hollow tubular and spiral shape with the microchannels facing inwardly. 3. Hydrogel films with different three-dimensional structures in cylinders.

Stimulus-triggered deformation experiment:

A. The spiral hydrogel film (45 °) with the microchannels facing inward in this example is placed in an aqueous solution of pH = 1. At this time, the pH of the system is less than the pKa of the carboxyl group, the carboxyl group is protonated, and the molecular segment is shrunk. The shrinkage of the system tightens the shrinkage of the hydrogel material. Gradually adjust the pH. When pH = 4.5, the carboxyl group is deprotonated, the molecular chain stretches, the system swells, the hydrogel material will gradually open and become flat, the pH further increases to 5, and the hydrogel will gradually bend in the opposite direction. A three-dimensional structure with microchannels facing outward is formed. When pH> 11 is strongly alkaline, calcium ions and hydroxides form insoluble substances, and the hydrogel material gradually disintegrates.

Example 11

A controllable bidirectional three-dimensional deformation hydrogel film, the surface of the hydrogel film has directionally arranged microchannels, and a degree of cross-linking gradient in thickness. The material of the hydrogel film is sodium alginate cross-linked by zinc ions. The microchannels have a depth of 5 μm and a width of 1 μm.

The method for preparing the controllable two-dimensional three-dimensional deformation hydrogel film includes the following steps:

(1) Rinse the silicon wafer with acetone, ethanol, and water in sequence. After purging with nitrogen, place the wafer in a plasma cleaner for 1 minute. The photoresist AZ 5214 was spin-coated on the surface of the silicon wafer at a rotation speed of 3000 r / m for 30 seconds, and then placed on a 95 ° C hot table for 30 seconds. Finally, a silicon-based template with a specific structure (length and width of 4 cm × 4 cm) is obtained after the photolithographic development process.

(2) A 1% sodium alginate aqueous solution is prepared, 0.5 mL is poured onto the silicon-based template obtained above, and it is left to stand at room temperature for 5 hours to form a uniform film layer. Subsequently, it was immersed in a 5mol / L Zn ²⁺ solution for pre-crosslinking for 10 minutes, and then the Zn ²⁺ ions were diffused and crosslinked from top to bottom to form a gradient crosslinking degree in the thickness direction. The pre-crosslinked film layer was peeled off from the silicon-based template to obtain a film layer with a plurality of microchannels aligned on one side surface, and cut along different angles of the microchannel (0 °, 45 °, 90 °). A 3.5 cm × 0.5 cm pre-crosslinked hydrogel sample was cut out. Finally, the obtained sample was completely cross-linked in a 10 mol / L Zn ²⁺ solution for 24 hours to form a hollow tubular, spiral, Hydrogel films with different three-dimensional structures in cylinders.

Stimulus-triggered deformation experiment:

A. The hollow tubular, spiral, and cylindrical bodies with three different three-dimensional structures are placed in a 0.1mmol / L EDTA solution for 24 hours. The EDTA will interact with Zn ²⁺ ions. Coordination chelation gradually replaces the Zn ²⁺ ion cross-linking sites, reduces the degree of cross-linking of the material, and triggers the swelling deformation of the hydrogel. Where the degree of cross-linking is small, the swelling rate is greater, forming a microchannel outward reaction. Different three-dimensional structures such as hollow tubular, spiral, and cylinder.

B. The spiral hydrogel film (45 °) with the microchannels facing inward obtained in this example is placed in a mixed solution of EDTA and Zn ^{2+ with} different volume fractions of 0.1 mol / L for 24 hours. The EDTA and Zn ²⁺ ions are used. Competition to precisely adjust the mechanical properties of the material, thereby effectively controlling the degree of deformation of the hydrogel material. When the volume fraction of EDTA increases from 0% to 80%, the inward spiral of the microchannel gradually opens into a flat two-dimensional hydrogel. When the volume fraction of EDTA increases further, the hydrogel will gradually swell in the opposite direction to form a channel. Outer reverse helix.

Example 12

A flexible microelectrode array includes a polyimide substrate having a thickness of 1 μm, an electrode structure disposed on one side of the substrate, and a stimulus response layer having a thickness of 1 μm chemically bonded to the other side of the substrate. The material of the stimulus response layer is a controllable two-dimensional three-dimensional deformation hydrogel film. The surface of the hydrogel film has directionally arranged microchannels and a cross-linking gradient in thickness. The hydrogel film is made of sodium alginate. Obtained by calcium ion cross-linking; wherein, the width of the microchannel is 800 μm and the depth is 100 μm.

The preparation process of the flexible microelectrode array is as follows:

(1) Preparation of hydrogel film

Take a polyimide-based flexible microelectrode array, place it in a 0.1mol / L NaOH solution for 2h, and then treat it with 0.1mol / L HCl for 30min, so that a large number of carboxyl functional groups are formed on the substrate surface; and then placed in EDC containing 0.1mol / L It reacts with 0.25mol / L pH = 6MES buffer for 1h to activate the carboxyl group; finally, it is placed in a PBS buffer solution (pH = 7.2) containing 1.65mol / L ethylenediamine to react for 2h, and the surface aminated flexible microspheres are obtained. Electrode array

An aqueous solution of sodium alginate with a mass fraction of 5% was prepared, and 1 mL was poured onto the silicon-based template obtained above, and allowed to stand at room temperature for 5 hours to form a uniform film layer. Subsequently, it was immersed in a 0.1 mol / L calcium chloride solution for 10 minutes for pre-crosslinking to form, and the gradient cross-linking degree in the thickness direction was formed by calcium ion diffusion cross-linking from top to bottom. The pre-crosslinked film layer was peeled off from the silicon-based template to obtain a film layer with a plurality of microchannels aligned on one side surface, and cut along different angles of the microchannel (0 °, 45 °, 90 °). A 3.5cm × 0.5cm pre-crosslinked hydrogel sample was cut out. Finally, the sample obtained by cutting at 0 °, 45 °, and 90 ° was completely crosslinked in a 0.1mol / L calcium chloride solution for 24h, respectively. Hydrogel films with different three-dimensional structures in the form of hollow tubes, spirals, and cylinders with the microchannels facing inward are formed.

(2) Preparation of stimulus response layer by surface chemical bonding

The hydrogel film prepared above is adhered to the back surface of the surface-aminated flexible microelectrode array (the microchannels face outward), and the free carboxyl group on the hydrogel surface undergoes an amidation reaction with the amino group on the surface of the flexible substrate to obtain a chemical bond. A stimulating response layer combined with the substrate surface drives the microelectrode array to form a flexible hollow electrode array with different three-dimensional structures in the form of a forward hollow tube, spiral, and cylinder with microchannels facing inward.

Ion-triggered deformation test:

When the flexible microelectrode array prepared in this embodiment is placed in a 0.1 mol / L sodium chloride solution for 24 hours, sodium ions will gradually replace the coordinated cross-linked calcium ions, reduce the degree of cross-linking of the material, and trigger the hydrogel. Swelling deformation, where the degree of cross-linking is small, the swelling ratio is greater, forming reverse hollow tubular, spiral, and cylindrical three-dimensional structures with outward microchannels, and driving the microelectrode array to form as shown in Figure 5 (a), ( b), (c) different three-dimensional structures of cylinder, spiral, hollow tube.

Example 13

A flexible microelectrode array includes a parylene substrate, an electrode structure disposed on one side of the substrate, and a stimulus response layer physically adhered on the other side of the substrate. The thickness of the parylene substrate was 5 mm, and the thickness of the stimulus response layer was 5 cm. The material of the stimulus-response layer is a controllable two-dimensional three-dimensional deformation hydrogel film obtained by gelatin cross-linking with calcium ions; wherein the width of the microchannel is 5 cm and the depth is 4.5 cm.

The preparation process of the flexible microelectrode array is as follows:

(1) Preparation of hydrogel film

The silicon wafer was cleaned with acetone, ethanol, and water in order. After being purged with nitrogen, it was placed in a plasma cleaner for 1 minute. The photoresist AZ 5214 was applied dropwise to the surface of the silicon wafer, and then placed on a 95 ° C hot stage for 30 seconds. Finally, a silicon-based template with a specific structure (length and width of 4 cm × 4 cm) is obtained after the photolithographic development process.

An aqueous gelatin solution with a mass fraction of 5% was prepared, and 1 mL was poured onto the silicon-based template obtained above, and allowed to stand at room temperature for 5 hours to form a uniform film layer. Subsequently, it was immersed in a 5 mol / L calcium chloride solution for 10 minutes for pre-crosslinking to form, and a gradient cross-linking degree in the thickness direction was formed by calcium ion diffusion cross-linking from top to bottom. The pre-crosslinked film layer was peeled off from the silicon-based template to obtain a film layer with a plurality of microchannels aligned on one side surface, and cut along different angles of the microchannel (0 °, 45 °, 90 °). A 3.5 cm × 0.5 cm pre-crosslinked hydrogel sample was cut out. Finally, the obtained sample was completely cross-linked in a 5 mol / L calcium chloride solution for 24 hours to form a hollow tubular, spiral, Hydrogel films with different three-dimensional structures in cylinders.

(2) Physically sticky stimulus response layer

The 502 glue was uniformly coated on the stimulation site of the flexible microelectrode array on a parylene substrate, and the hydrogel film prepared above was bonded to the stimulation site of the flexible microelectrode array. After the glue was dried, the stimulation response layer was driven The microelectrode array forms a flexible microelectrode array with different three-dimensional structures of forward hollow tubular, spiral, and cylindrical bodies with the microchannels facing inward.

Ion-triggered deformation test:

A. When the flexible microelectrode array prepared in this example is placed in a 2.5 mol / L sodium chloride solution for 24 hours, sodium ions will completely replace the coordinated cross-linked calcium ions, break all the cross-linking sites, and trigger hydrocoagulation. When the gel disintegrates, the electrode will return to its original flat state.

B. The flexible microelectrode array (45 °) prepared in this embodiment is placed in a sodium-calcium mixed solution with different volume fractions of 0.1mol / L for 24 hours, and the mechanical properties of the materials are precisely adjusted by the competition of sodium-calcium ions, so that Effectively control the degree of deformation of the hydrogel material. When the volume fraction of sodium ions increases from 0% to 98%, the inward spiral of the microchannel gradually opens into a flat two-dimensional hydrogel. When the volume fraction of sodium ions further increases, the hydrogel will gradually swell in the opposite direction. The outward spiral structure of the channel outwards drives the microelectrode array to deform.

Example 14

A flexible microelectrode array includes a polydimethylsiloxane substrate, an electrode structure disposed on one side of the substrate, and a stimulus response layer physically adhered to the other side of the substrate. The thickness of the polydimethylsiloxane substrate is 1 mm, and the thickness of the stimulus response layer is 1 mm. The material of the stimulus response layer is a controllable two-dimensional three-dimensional deformation hydrogel film obtained from polyacrylic acid through iron ion cross-linking; wherein the width of the microchannel is 5mm and the depth is 1mm.

The preparation process of the flexible microelectrode array is as follows:

(1) Preparation of hydrogel film

The silicon wafer was cleaned with acetone, ethanol, and water in order. After being purged with nitrogen, it was placed in a plasma cleaner for 1 minute. Photoresist SU-83050 was applied dropwise to the surface of a clean silicon wafer to form a photoresist layer with a thickness of 1 mm, and then placed on a 95 ° C hot stage for 30 seconds. Finally, a silicon-based template with a specific structure (length and width of 4 cm × 4 cm) is obtained after the photolithographic development process.

A 5% polyacrylic acid aqueous solution was prepared, and 5 mL was poured onto the silicon-based template obtained above, and allowed to stand at room temperature for 5 hours to form a uniform film layer. Subsequently, it was immersed in a 2.5mol / L Fe ³⁺ solution for pre-crosslinking for 10 minutes, and the gradient cross-linking degree in the thickness direction was formed by diffusion cross-linking of iron ions from top to bottom. The pre-crosslinked film layer was peeled off from the silicon-based template to obtain a film layer with a plurality of microchannels aligned on one side surface, and cut along different angles of the microchannel (0 °, 45 °, 90 °). A 3.5 cm × 0.5 cm pre-crosslinked hydrogel sample was cut out. Finally, the obtained sample was completely cross-linked in a 2.5 mol / L Fe ³⁺ solution for 24 hours to form a hollow tubular and spiral shape with the microchannels facing inward. 3. Hydrogel films with different three-dimensional structures in cylinders.

(2) Physically sticky stimulus response layer

502 glue was evenly coated on the front surface of the flexible microelectrode array substrate (the side with the electrode structure), and the hydrogel film prepared above was bonded to the front surface of the flexible microelectrode array. After the glue evaporates, the stimulus response layer drives the micro The electrode array forms a flexible hollow electrode array with different three-dimensional structures of forward hollow tubular, spiral, and cylindrical bodies with the microchannels facing inward.

Ion-triggered deformation test:

A. When the flexible microelectrode array prepared in this embodiment is placed in a 0.25mol / L Ag ⁺ solution for 24 hours, silver ions will gradually replace Fe ³⁺ ions coordinated to the carboxyl segment, reducing the degree of cross-linking of the material. The swelling deformation of the hydrogel is triggered, and the swelling rate is higher in the place with a small degree of cross-linking, forming different hollow three-dimensional structures such as inverted hollow tubes, spirals, and cylinders with outward microchannels, which drives the deformation of the flexible microelectrode array.

B, Preparation flexible microelectrode array of the present embodiment will be obtained (45 °) placed 0.05mol / L different concentrations of Ag ^+, Fe ³⁺ ion mixture 24h, the use of Ag ^+, Fe ³⁺ ions competitive effect To precisely adjust the mechanical properties of the material, so as to effectively control the degree of deformation of the hydrogel material. When the volume fraction of Ag ⁺ ions increases from 0% to 75%, the inward spiral of the microchannel gradually opens into a flat two-dimensional hydrogel. When the volume fraction of Ag ⁺ ions increases further, the hydrogel will gradually reverse Swelling forms a reverse spiral structure with channels outward, driving the deformation of the microelectrode array.

Example 15

A flexible microelectrode array includes a polyimide substrate, an electrode structure disposed on one side of the substrate, and a stimulus response layer chemically bonded on the other side of the substrate. The thickness of the polyimide substrate was 1 μm, and the thickness of the stimulus response layer was 1 μm. The material of the stimulus-response layer is a controllable two-dimensional three-dimensional deformation hydrogel film obtained from sodium alginate through calcium ion cross-linking; wherein the width of the microchannel is 800 μm and the depth is 100 μm.

The preparation process of the flexible microelectrode array is as follows:

(1) Preparation of hydrogel film

Take a polyimide-based flexible microelectrode array, place it in a 0.1mol / L NaOH solution for 2h, and then treat it with 0.1mol / L HCl for 30min, so that a large number of carboxyl functional groups are formed on the substrate surface; and then placed in EDC containing 0.1mol / L It reacts with 0.25mol / L pH = 6MES buffer for 1h to activate the carboxyl group; finally, it is placed in a PBS buffer solution (pH = 7.2) containing 1.65mol / L ethylenediamine to react for 2h, and the surface aminated flexible microspheres are obtained. Electrode array

An aqueous solution of sodium alginate with a mass fraction of 5% was prepared, and 1 mL was poured onto the silicon-based template obtained above, and allowed to stand at room temperature for 5 hours to form a uniform film layer. Subsequently, it was immersed in a 0.1 mol / L calcium chloride solution for 10 minutes for pre-crosslinking to form, and the gradient cross-linking degree in the thickness direction was formed by calcium ion diffusion cross-linking from top to bottom. The pre-crosslinked film layer was peeled off from the silicon-based template to obtain a film layer with a plurality of microchannels aligned on one side surface, and cut along different angles of the microchannel (0 °, 45 °, 90 °). A 3.5cm × 0.5cm pre-crosslinked hydrogel sample was cut out. Finally, the sample obtained by cutting at 0 °, 45 °, and 90 ° was completely crosslinked in a 0.1mol / L calcium chloride solution for 24h, respectively. Hydrogel films with different three-dimensional structures in the form of hollow tubes, spirals, and cylinders with the microchannels facing inward are formed.

(2) Preparation of stimulus response layer by surface chemical bonding

The hydrogel film prepared above was adhered to the back surface of the surface aminated flexible microelectrode array, and the free carboxyl group on the hydrogel surface was subjected to an amidation reaction with the amino group on the surface of the flexible substrate to obtain A stimulating response layer that drives the microelectrode array to form a flexible hollow electrode array with different three-dimensional structures in the form of a forward hollow tube, spiral, and cylinder with microchannels facing inward.

pH-triggered deformation test:

The flexible microelectrode array prepared in this embodiment is placed in an aqueous solution of pH = 1, at this time, the pH of the system is lower than the pKa of the carboxyl group, the carboxyl group is protonated, the molecular segment is shrunk, and the shrinkage of the system makes the hydrogel material shrink and tighten. The pH is gradually adjusted. When pH = 4.5, the carboxyl group is deprotonated, the molecular chain stretches, and the system swells. The hydrogel material will gradually open and become flat, which will drive the electrode to flatten. It will gradually bend in the opposite direction to form a three-dimensional structure with the microchannels facing outward, which will drive the electrodes to deform in the opposite direction. When pH> 11 is strongly alkaline, calcium ions and hydroxides form insoluble matter, the hydrogel material gradually disintegrates, and the electrode returns to a flat state.

Example 16

A flexible microelectrode array includes a parylene substrate, an electrode structure disposed on one side of the substrate, and a stimulation response layer physically adhered to a stimulation site of the substrate. The thickness of the parylene substrate was 5 mm, and the thickness of the stimulus response layer was 5 cm. The material of the stimulus response layer is a controllable two-dimensional three-dimensional deformation hydrogel film, and the hydrogel film is obtained by sodium alginate cross-linking with zinc ions. The microchannel has a depth of 5 μm and a width of 1 μm.

The preparation process of the flexible microelectrode array is as follows:

(1) Preparation of hydrogel film

The silicon wafer was cleaned with acetone, ethanol, and water in order. After being purged with nitrogen, it was placed in a plasma cleaner for 1 minute. The photoresist AZ 5214 was spin-coated on the surface of the silicon wafer at a rotation speed of 3000 r / m for 30 seconds, and then placed on a 95 ° C hot table for 30 seconds. Finally, a silicon-based template with a specific structure (length and width of 4 cm × 4 cm) is obtained after the photolithographic development process.

An aqueous solution of sodium alginate with a mass fraction of 5% was prepared, and 1 mL was poured onto the silicon-based template obtained above, and allowed to stand at room temperature for 5 hours to form a uniform film layer. Subsequently, it was immersed in a 10mol / L Zn ²⁺ solution for pre-crosslinking for 10 minutes to form a gradient cross-linking degree in the thickness direction by diffusion cross-linking of Zn ²⁺ ions from top to bottom. The pre-crosslinked film layer was peeled off from the silicon-based template to obtain a film layer with a plurality of microchannels aligned on one side surface, and cut along different angles of the microchannel (0 °, 45 °, 90 °). A 3.5 cm × 0.5 cm pre-crosslinked hydrogel sample was cut out. Finally, the obtained sample was completely cross-linked in a 10 mol / L Zn ²⁺ solution for 24 hours to form a hollow tubular, spiral, Hydrogel films with different three-dimensional structures in cylinders.

(2) Physically sticky stimulus response layer

The 502 glue was uniformly coated on the stimulation site of the flexible microelectrode array on a parylene substrate, and the hydrogel film prepared above was bonded to the stimulation site of the flexible microelectrode array. After the glue was dried, the stimulation response layer was driven The microelectrode array forms a flexible microelectrode array with different three-dimensional structures of forward hollow tubular, spiral, and cylindrical bodies with the microchannels facing inward.

Deformation test by coordination chelation:

When the flexible microelectrode array prepared in this embodiment is placed in a 0.1mmol / L EDTA solution for 24 hours, the EDTA will coordinate with the Zn ²⁺ ions, gradually replacing the Zn ²⁺ ion crosslinking sites, and reducing the cross-linking of the material. The degree of connection triggers the swelling deformation of the hydrogel, where the degree of swelling is small, and the swelling rate is greater, forming different hollow three-dimensional structures such as inverted hollow tubes, spirals, and cylinders with outward microchannels, driving the flexible microelectrode array. deformation.

The flexible microelectrode array (45 °) prepared in this embodiment was placed in a mixed solution of EDTA and Zn ^{2+ with} different volume fractions of 0.1 mol / L for 24 hours, and the competition of EDTA and Zn ²⁺ ions was used to precisely adjust the material. Mechanical properties to effectively control the degree of deformation of the hydrogel material. When the volume fraction of EDTA increases from 0% to 80%, the inward spiral of the microchannel gradually opens into a flat two-dimensional hydrogel, and the electrode returns to a flat state. When the volume fraction of EDTA further increases, the hydrogel will gradually The reverse swelling forms a reverse spiral structure with outward channels, which drives the reverse deformation of the flexible electrode.

It should be noted that, according to the disclosure and description of the foregoing description, those skilled in the art to which the present invention pertains can also make changes and modifications to the above embodiments. Therefore, the present invention is not limited to the specific embodiments disclosed and described above, and equivalent modifications and changes to the present invention should also fall within the protection scope of the claims of the present invention. In addition, although some specific terms are used in this specification, these terms are only for convenience of explanation and do not constitute any limitation to the present invention.

Claims (17)

A controllable two-dimensional three-dimensional deformation hydrogel film, characterized in that the hydrogel film is formed of a carboxyl group-containing polymer through divalent or trivalent cation cross-linking, and the hydrogel film is cross-linked in the thickness direction. Degree gradient, one side surface of the hydrogel film is provided with a plurality of aligned microchannels, and the hydrogel film is curled toward a side having the microchannels to generate a positive deformation. The hydrogel film according to claim 1, wherein the carboxyl group-containing polymer comprises sodium alginate, gelatin, hyaluronic acid, chitosan, cellulose, carboxymethyl cellulose, and carboxymethyl crust Pigment, starch, protein, polymethacrylic acid, polyacrylic acid, carboxylic acid terminated poly (N-isopropylacrylamide), poly-L-glutamic acid, polyhistidine, polyaspartic acid, polyethyl Acrylic acid, polypropyl acrylic acid, polyvinyl benzoic acid, polyitaconic acid, peptidoglycan, glutathione, diglycine, elastin-like polypeptide, carboxylated polyvinyl alcohol, carboxylated polypropylene glycol, carboxylated polyethylene Diol, poly (4-carboxybenzenesulfonamide), poly [(R) -3-hydroxybutyric acid], polysebacic acid, polymaleic anhydride, poly-DL-alanine, poly-DL-lysine Acid, poly-DL-ornithine, poly-L-arginine, poly-L-proline, polyglycolic acid, polyglycine, poly (1,3-propenyl adipate), poly (1,3- One or more of propylene glutaric acid), poly (1,3-propylene succinic acid), polyepoxysuccinic acid, other carboxyl-containing polymers, and derivatives and copolymers containing the above units. The hydrogel film according to claim 1, wherein the thickness of the hydrogel film is 1 m to 5 cm. The hydrogel film according to claim 1, wherein the microchannels are evenly arranged on one surface of the hydrogel film, and the width of the microchannels is 10nm-5cm. The depth is 10nm-4.5cm. The hydrogel film according to claim 1, wherein the formation of a cross-linking degree gradient in the thickness direction of the hydrogel film is specifically: the degree of cross-linking of the hydrogel film is determined by The surface from one side to the opposite surface gradually increases, and the cross-linking gradient causes the hydrogel film to form a difference in Young's modulus in the thickness direction, and the difference is in the range of 0.0001 Pa-2000 Gpa. The hydrogel film according to claim 1, wherein the divalent cation is Ca ²⁺ , Mg ²⁺ , Ba ²⁺ , Cu ²⁺ , Be ²⁺ , Sr ²⁺ , Ra ²⁺ , One of Fe ²⁺ , Co ²⁺ , Ni ²⁺ , Zn ²⁺ , Hg ²⁺ , Cr ²⁺ , Cd ²⁺ , Pd ²⁺ , Pt ²⁺ , Sn ²⁺ , Pb ²⁺ , Mn ²⁺ Or more. The hydrogel film according to claim 1, wherein the trivalent cation is Fe ³⁺ , Al ³⁺ , Bi ³⁺ , Sc ³⁺ , La ³⁺ , Pr ³⁺ , Gd ³⁺ , One or more of Co ³⁺ and Ce ³⁺ . The hydrogel film according to claim 1, wherein the degree of the positive deformation can be adjusted by controlling the concentration of the divalent or trivalent cation solution and the crosslinking time during the crosslinking process. Or the concentration of trivalent cation solution is 0.1mmol / L-10mol / L. The hydrogel film according to claim 1, wherein when the hydrogel film is placed in a monovalent cation solution or a mixed solution of a monovalent cation and a divalent or trivalent cation, the hydrogel film is The hydrogel film is curled toward the side where the microchannel is not provided to generate reverse deformation, and further increasing the concentration of the monovalent cation can completely dissolve the hydrogel film. The hydrogel film according to claim 9, wherein the monovalent cation is one or more of Na ⁺ , K ⁺ , Rb ⁺ , Cs ⁺ , Fr ⁺ , and Ag ⁺ , so that The concentration range of the monovalent cation solution that produces reverse deformation of the hydrogel film is 0.1mmol / L-10mol / L; the concentration range of the monovalent cation solution that completely dissolves the hydrogel is 0.25mol / L-10mol / L. L. The hydrogel film according to claim 1, wherein the hydrogel film can realize a controllable two-dimensional three-dimensional deformation by adjusting the pH, and the pH range is 1-14. The hydrogel film according to claim 1, wherein the hydrogel film can achieve a controlled two-dimensional three-dimensional deformation by chelation coordination of a chelating agent with a divalent or trivalent cation, bonding agents include EDTA, citric _{^{acid, SO 4 2-, cO 3 2-}} , HCO 3 -, CH 3 COO -, C 2 O 4 2-, MnO 4 - of one or more of the chelating agent The concentration range is 0.1mmol / L-10mol / L. A method for preparing a controllable two-dimensional three-dimensional deformation hydrogel film, which comprises the following steps: Provide a template with a specific structure; A carboxyl-containing polymer solution is prepared, the carboxyl-containing polymer solution is poured onto the template, and after being left to form a film, the template is immersed in a divalent or trivalent cation solution to make the The carboxyl-containing polymer film layer is pre-crosslinked, and the divalent or trivalent cations are diffused and crosslinked from top to bottom, so that the carboxyl-containing polymer film layer forms a cross-linking gradient in the thickness direction, and the carboxyl-containing polymer film layer is formed. The polymer film layer is peeled off from the surface of the template, and a surface of one side of the carboxyl group-containing polymer film layer near the template forms a plurality of microchannels arranged in an array; The carboxyl-containing polymer film layer is sheared at different angles along the long axis of the microchannel, and then placed in the divalent or trivalent cation solution for complete cross-linking to obtain a hydrogel film. The adhesive film is curled toward a side having the microchannel to generate a positive deformation, and a stable three-dimensional structure is obtained. The preparation method according to claim 13, characterized in that shearing is performed at an angle of 0 °, 45 °, or 90 ° to the long axis of the microchannel, and a hollow tube and a spiral shape are obtained after being completely crosslinked. And hollow cylindrical three-dimensional structure hydrogel film. A flexible microelectrode array, comprising a flexible substrate, an electrode structure disposed on one side of the flexible substrate, and a stimulus response layer provided at any part of the flexible substrate. The material of the stimulus response layer is claim 1 The controllable two-dimensional three-dimensional deformation hydrogel film according to any one of -12. The flexible microelectrode array according to claim 15, wherein a thickness of the flexible substrate is 1 μm to 5 mm, and a thickness of the stimulus response layer is 1 μm to 5 cm. The flexible microelectrode array according to claim 15, wherein the stimulus-responsive layer is modified on the flexible substrate by surface chemical bonding or physical sticking.

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