Amino-functionalized agarose self-healing gels, methods of making and using the same

Abstract

This invention belongs to the field of polysaccharide gel materials, specifically relating to amino-functionalized agarose self-healing gel, its preparation method, and its applications. The method involves dissolving agarose in dimethyl sulfoxide (DMSO), and then, under a nitrogen atmosphere, mixing the agarose DMSO solution with dissolved... N , N Agarose was modified by mixing α-carbonyl diimidazole with a DMSO solution and then coupled with aldehyde small molecules, deionized water / ionic liquid / eutectic solvent to prepare AG-NH2 Schiff base self-healing hydrogels, AG-NH2 Schiff base self-healing ionic gels, AG-NH2 self-healing ionic gels, and AG-NH2 Schiff base self-healing eutectic gels, respectively. These self-healing gels improved the stability of the gel materials and extended their service life. Application of these self-healing gels in epidermal electrodes for monitoring ECG and electromyography signals showed significantly better sensing performance than commercial electrodes.

Description

Technical Field

[0001] This invention belongs to the field of polysaccharide gel materials, and relates to the preparation method of self-healing gel and its application in epidermal electrodes. Background Technology

[0002] Polysaccharides are natural polymers formed by monosaccharides linked by glycosidic bonds, such as agarose, chitosan, and hyaluronic acid. Agarose (AG), as a neutral polysaccharide, is rich in hydroxyl groups and is easily chemically modified, such as by introducing amino groups, to construct functionalized gel networks. Self-healing gels are soft materials that can repair themselves after damage, and can be classified into non-autonomous and autonomous types according to their mechanisms. Among them, chemically cross-linked gels based on dynamic covalent bonds such as imine bonds have greater application potential than physically cross-linked gels due to their high healing efficiency and good stability.

[0003] Traditional hydrogels suffer from problems such as solvent volatility, poor stability, and narrow operating temperature range, which limits their applications. Therefore, improvements are needed to address these shortcomings. Summary of the Invention

[0004] To address the technical challenges of poor stability and limited applications of self-healing hydrogels, this invention functionally modifies widely available and biocompatible agarose to obtain amino-functionalized agarose with strong gelling capabilities, and prepares self-healing gel materials in various solvents. Using ionic liquids or eutectic solvents as media can significantly improve the gel's conductivity, environmental stability, and operating temperature range, making it particularly suitable for scenarios requiring long-term stable operation, such as electrophysiological signal sensing.

[0005] Specifically, this invention introduces aldehyde small molecules into the gel material, utilizing the Schiff base reaction between the aldehyde group and the functionalized agarose amino group to generate dynamic imine bonds, supplemented by hydrogen bonds, to endow the gel with self-healing function, improve the stability of the gel material, and extend its service life. The prepared self-healing gel, when used as an electrode patch, shows significantly better sensing performance than commercial electrodes in human electrophysiological signal monitoring applications.

[0006] The amino-functionalized agarose self-healing gel provided by this invention refers to any one of the following: AG-NH2 Schiff base self-healing hydrogel, AG-NH2 Schiff base self-healing ionic gel, AG-NH2 self-healing ionic gel, and AG-NH2 Schiff base self-healing eutectic gel. Among them, the AG-NH2 Schiff base self-healing hydrogel is prepared using amino-modified agarose AG-NH2, aldehyde small molecules, and deionized water as the main raw materials. The AG-NH2 Schiff base self-healing ionic gel was prepared using amino-modified agarose AG-NH2, aldehyde small molecules, and ionic liquid 1-ethyl-3-methylimidazolium acetate [EMIM][OAc] as the main raw materials. The AG-NH2 self-healing ionic gel was prepared using amino-modified agarose AG-NH2 and ionic liquid 1-ethyl-3-methylimidazolium acetate [EMIM][OAc] as the main raw materials. The AG-NH2 Schiff base self-healing eutectic gel was prepared using amino-modified agarose AG-NH2, aldehyde small molecules, and eutectic solvent as the main raw materials.

[0007] The aforementioned aldehyde molecules are selected from any one of 50 wt% glutaraldehyde aqueous solution, 40 wt% acetone aldehyde aqueous solution, and pyromellitic methyl ether.

[0008] The synthesis method of amino-modified agarose AG-NH2 is as follows: (1) Heat and stir agarose AG to dissolve it in dimethyl sulfoxide (DMSO); the mass ratio of agarose to DMSO is 1.2:100. (2) Under N2 atmosphere, N , N - Carbonyl diimidazole (CDI) was added to dimethyl sulfoxide (DMSO) and stirred at room temperature until... N , N -Carbonyl diimidazole is completely dissolved; N , N - The mass ratio of carbonyl diimidazole (CDI) to dimethyl sulfoxide (DMSO) is 10.8:100; (3) Take the material dissolved in (1) and quickly add it to the solution dissolved in (2). Stir at room temperature for 2 h. Then add excess ethylenediamine and stir in the dark for 24 h. Dialyze and freeze dry to obtain amino-modified agarose AG-NH2. During dialysis, the molecular weight cutoff of the dialysis bag is 8000-14000 Da. Dialyze for 72 h and freeze dry for 48 h.

[0009] When the self-healing gel is an AG-NH2 Schiff base self-healing hydrogel, its preparation method is as follows: S1-1: Add amino-agarose AG-NH2 to deionized water and heat to 70 °C. Stir for 30 min to dissolve it, then cool to room temperature to obtain solution I. The mass ratio of amino-agarose AG-NH2 to deionized water is 1.5-2.5:100. S1-2: Under room temperature vortex conditions, mix 50 wt% glutaraldehyde aqueous solution and deionized water to obtain solution II, keeping the mass ratio of glutaraldehyde to amino-agarose AG-NH2 at 2:100-1:2; Alternatively, mix 40 wt% acetone aldehyde aqueous solution with deionized water to obtain solution II, keeping the mass ratio of acetone aldehyde to amino-agarose AG-NH2 at 5:100 or 1:1; Alternatively, mix pyromellitic aldehyde and methanol to obtain solution II, maintaining the mass ratio of pyromellitic aldehyde to amino-agarose AG-NH2 at 5:100; S1-3: Under room temperature vortex conditions, solution II is added dropwise to solution I to mix the two, thus obtaining AG-NH2 Schiff base self-healing hydrogel.

[0010] When the self-healing gel is an AG-NH2 Schiff base self-healing ionic gel, its preparation method is as follows: S2-1: Heat and stir at 110 °C for 1-2 min to dissolve amino-agarose AG-NH2 in ionic liquid 1-ethyl-3-methylimidazolium acetate [EMIM][OAc] to obtain a clear and transparent liquid, and cool to room temperature; the mass ratio of amino-agarose AG-NH2 to ionic liquid 1-ethyl-3-methylimidazolium acetate [EMIM][OAc] is 2:100. S2-2: Under vortex action, add 50 wt% glutaraldehyde aqueous solution to the material cooled by S1, mix thoroughly and evenly, and let stand to obtain AG-NH2 Schiff base self-healing ion gel; the mass ratio of glutaraldehyde to amino-agarose AG-NH2 is 1:2-2:1.

[0011] When the self-healing gel is an AG-NH2 self-healing ionic gel, its preparation method is as follows: S2-3: Heat and stir at 110 °C for 30 min to dissolve amino-agarose AG-NH2 in ionic liquid 1-ethyl-3-methylimidazolium acetate [EMIM][OAc] to obtain a clear and transparent liquid. Cool to room temperature to obtain AG-NH2 self-healing ionic gel; the mass ratio of amino-agarose AG-NH2 to ionic liquid 1-ethyl-3-methylimidazolium acetate [EMIM][OAc] is 3:100.

[0012] When the self-healing gel is an AG-NH2 Schiff base self-healing eutectic gel, its preparation method is as follows: S3-1: Aminated agarose AG-NH2 and eutectic solvent choline chloride / lactic acid ChCl / LA are heated to 110°C and stirred for 1-2 min to obtain a clear and transparent liquid, which is then cooled to room temperature; the mass ratio of aminated agarose AG-NH2 to eutectic solvent ChCl / LA is 2:100; the eutectic solvent ChCl / LA is a clear and transparent liquid obtained by heating choline chloride and lactic acid in a molar ratio of 1:2 at 90°C for 5 min. S3-2: Under vortex action, 50 wt% glutaraldehyde aqueous solution is added to the material cooled in S1, and after thorough mixing and standing, AG-NH2 Schiff base self-healing eutectic gel is obtained; the mass ratio of glutaraldehyde to amino-agarose AG-NH2 is 1:2.

[0013] The application of the above-mentioned amino-functionalized agarose self-healing gel in flexible epidermal electrodes is also within the scope of protection of this invention.

[0014] Preferably, the aforementioned flexible epidermal electrode is an electrode for monitoring electrophysiological signals.

[0015] Specifically, the electrode can be either a skin electrode for monitoring electrocardiogram (ECG) signals or a skin electrode for monitoring electromyogram (EMG) signals.

[0016] The beneficial effects of this invention are as follows: (1) This invention introduces ionic liquid [EMIM][OAc] and eutectic solvent (such as ChCl / LA) as dispersion medium, which greatly improves thermal stability and environmental adaptability. Its thermal decomposition temperature can reach 219 ℃, and it has good low temperature tolerance, expanding its application potential in a wide temperature range of -70~-80 ℃ to 200 ℃. (2) Dynamic imine bonds are formed by Schiff base reaction, which enables the gel to heal rapidly and autonomously after damage. Macroscopic experiments show that it can achieve significant healing within 5 s to 3 min and has excellent injectability. After being broken, it can be reshaped into a complete shape by injection. (3) By adjusting the type and ratio of crosslinking agents, the mechanical properties and adhesion strength of the gel can be effectively adjusted. It has significant adhesion to the surface of various materials (such as skin, glass, stainless steel, etc.), and the adhesion is stable. It can maintain reliable adhesion even after being repeatedly pasted 20 times. (4) In electrophysiological signal monitoring, the gel electrode exhibits lower interfacial impedance and higher signal-to-noise ratio than commercial Ag / AgCl electrodes. It is stable and responsive in ECG and EMG tests, and is suitable for long-term health monitoring and flexible electronic sensing.

[0017] (5) The self-healing gel of the present invention uses natural agarose as raw material, which is abundant, inexpensive and biocompatible. The introduction of amino groups through chemical modification significantly enhances the reactivity and gelation ability. Attached Figure Description

[0018] Figure 1 The synthesis reaction formula for AG-NH2; Figure 2 In the diagram, A represents the Fourier Transform Infrared (FT-IR) spectra of AG and AG-NH2; B represents the X-ray Diffraction (XRD) curves of AG and AG-NH2; and C represents the X-ray Photoelectron Spectroscopy (XPS) curve of AG-NH2. Figure 3In the table, A represents the transmittance curves of different self-healing gels in Examples 1, 4, 5, and 7; B represents the thermogravimetric analysis (TGA) curves of glutaraldehyde self-healing hydrogel, ionic liquid [EMIM][OAc], glutaraldehyde self-healing ionic gel, self-healing pure ionic gel, eutectic solvent ChCl / LA, and glutaraldehyde self-healing eutectic gel in Examples 1, 4, 5, and 7; C represents the differential scanning calorimetry (DSC) curve of glutaraldehyde self-healing hydrogel in Example 1; and D represents the DSC curves of ionic liquid [EMIM][OAc], glutaraldehyde self-healing ionic gel, self-healing pure ionic gel, eutectic solvent ChCl / LA, and glutaraldehyde self-healing eutectic gel in Examples 4, 5, and 7. Figure 4 In the diagram, A represents the adhesion test image of glutaraldehyde self-healing hydrogel in Example 1 on different materials; B represents the adhesion test image of acetone aldehyde self-healing hydrogel in Example 2 on different materials; C represents the adhesion test image of trimesoaldehyde self-healing hydrogel in Example 3 on different materials; D represents the adhesion test image of glutaraldehyde self-healing ionic gel in Example 4 on different materials; E represents the adhesion test image of pure self-healing ionic gel in Example 5 on different materials; and F represents the adhesion test image of trimesoaldehyde self-healing ionic gel in Example 6 on different materials. Figure 5 In the diagram, A is a macroscopic self-healing test image of the glutaraldehyde self-healing hydrogel in Example 1; B is a microscopic self-healing test image of the glutaraldehyde self-healing hydrogel in Example 1; and C is an injectability test image of the glutaraldehyde self-healing hydrogel in Example 1. Figure 6 In the diagram, A is a macroscopic self-healing test image of the acetone aldehyde self-healing hydrogel in Example 2; B is an injectability test image of the acetone aldehyde self-healing hydrogel in Example 2. Figure 7 In the diagram, A is a macroscopic self-healing test image of the pyromellitic trimethylolpropionic acid self-healing hydrogel of Example 3; B is an injectability test image of the pyromellitic trimethylolpropionic acid self-healing hydrogel of Example 3. Figure 8 In the diagram, A is a macroscopic self-healing test image of the glutaraldehyde self-healing ion gel in Example 4; B is a microscopic self-healing test image of the glutaraldehyde self-healing ion gel in Example 4; and C is an injectability test image of the glutaraldehyde self-healing ion gel in Example 4. Figure 9 In the diagram, A is a macroscopic self-healing test image of the self-healing pure ion gel of Example 5; B is a microscopic self-healing test image of the self-healing pure ion gel of Example 5; and C is an injectability test image of the self-healing pure ion gel of Example 5. Figure 10 In the diagram, A is a macroscopic self-healing test image of the trimethylbenzene ionogel from Example 6; B is an injectability test image of the trimethylbenzene ionogel from Example 6. Figure 11 In the diagram, A represents the infrared spectrum of the imine bonds in the glutaraldehyde self-healing hydrogel of Example 1; B represents the infrared spectrum of the imine bonds in the glutaraldehyde self-healing ion gel of Example 4; C represents the steady-state shearing result of the glutaraldehyde self-healing hydrogel of Example 1; and D represents the continuous step strain scanning result of the glutaraldehyde self-healing ion gel of Example 4. Figure 12 In the table, A shows the stress scan comparison results of glutaraldehyde self-healing hydrogel, glutaraldehyde self-healing ionic gel, and glutaraldehyde self-healing eutectic gel in Comparative Examples 2, 4, and 7; B shows the conductivity test results of glutaraldehyde self-healing hydrogel, ionic liquid [EMIM][OAc], glutaraldehyde self-healing ionic gel, and self-healing pure ionic gel in Examples 1, 4, and 5; C shows the interfacial impedance comparison diagram of glutaraldehyde self-healing hydrogel, glutaraldehyde self-healing ionic gel, and self-healing pure ionic gel in Examples 1, 4, and 5 with commercial Ag / AgCl electrode on the skin. Figure 13 In the table, A represents the ECG signal test results of glutaraldehyde self-healing hydrogel, glutaraldehyde self-healing ion gel, and self-healing pure ion gel with commercial Ag / AgCl electrode in Examples 1, 4, and 5; B represents the ECG signal test results of glutaraldehyde self-healing ion gel and self-healing pure ion gel with commercial Ag / AgCl electrode after seven days of placement in Examples 4 and 5. Figure 14 In the table, A represents the ECG signal test results of the glutaraldehyde self-healing ion gel in Example 4 after repeated application and use; B represents the ECG signal test results of the commercial Ag / AgCl electrode after repeated application and use. Figure 15 In the table, A represents the electromyography (EMG) signal test results of the glutaraldehyde self-healing ionogel electrode in Example 4 under rest / vibration conditions; B represents the EMG signal test results of the self-healing pure ionogel electrode in Example 5 under rest / vibration conditions; and C represents the EMG signal test results of the self-healing pure ionogel electrode in Example 5 under different grip forces. Detailed Implementation

[0019] Example 1 (1) Synthesis of AG-NH2: 0.1 g of agarose was dissolved in 7.5 mL of DMSO under heating and stirring at 110 °C (i.e., the mass ratio of agarose to DMSO was 1.2:100) and set aside. Under a N2 atmosphere, 4.77 g of CDI was added to 40 mL of DMSO (i.e., the mass ratio of CDI to DMSO was 10.8:100), and stirred at room temperature until completely dissolved. The agarose solution was then quickly added, and the mixture was stirred at room temperature for 2 h. 10 mL of 98% ethylenediamine was added to the resulting solution, and the mixture was stirred in the dark for 24 h. After dialyzing for 72 h, the mixture was lyophilized for 48 h to obtain AG-NH2. (2) Preparation of AG-NH2 Schiff base self-healing hydrogel: 1 g of AG-NH2 (i.e., the mass ratio of AG-NH2 to deionized water is 2:100) was added to 30 mL of deionized water, heated and stirred at 70 °C to dissolve, and cooled to room temperature to obtain solution I, which was set aside for use; under room temperature vortex conditions, 36 µL of 50 wt% glutaraldehyde aqueous solution and 20 mL of deionized water were mixed to obtain solution II (i.e., the mass ratio of glutaraldehyde to AG-NH2 is 2:100), which was set aside for use; under room temperature vortex conditions, solution II was added dropwise to solution I to obtain AG-NH2 Schiff base self-healing hydrogel. The self-healing hydrogel described above, when completely separated into two pieces under external force, showed obvious healing within 10 seconds after being put back together, and the healed gel had a certain strength. Microscopically, when magnified 20× by an optical microscope, the damaged hydrogel could be completely healed within 15 minutes. The damaged gel could be squeezed out with a No. 23 syringe to form a gel with a complete shape, showing excellent injectability. The glutaraldehyde self-healing hydrogel can adhere to various materials such as silicone, iron, glass, paper, skin and wood, showing good adhesion.

[0020] Example 2 The difference from Example 1 is that the aldehyde molecule added in (2) is a 40 wt% acetone aldehyde aqueous solution (i.e., the mass ratio of acetone aldehyde to AG-NH2 is 5:100 or 1:1), and the other steps are the same as in Example 1. The macroscopic experimental effects, properties and adhesion of the acetone aldehyde self-healing hydrogel are similar to those of the glutaraldehyde self-healing hydrogel in Example 1.

[0021] Example 3 The difference from Example 1 is that (2) a methanol solution of 2 mL of pyromellitic aldehyde (i.e., the mass ratio of pyromellitic aldehyde to AG-NH2 is 5:100) is added. The pyromellitic aldehyde self-healing hydrogel described in this example shows obvious healing after the two broken hydrogels come into contact for 3 min, and the healed gel does not separate under gravity, exhibiting a certain strength; other properties of the pyromellitic aldehyde self-healing hydrogel are similar to those of the glutaraldehyde self-healing hydrogel in Example 1.

[0022] Example 4 (1) Dissolve 0.1 g agarose in 7.5 mL DMSO under heating and stirring at 110 °C (i.e., the mass ratio of agarose to DMSO is 1.2:100) and set aside. Under N2 atmosphere, add 4.77 g CDI to 40 mL DMSO (i.e., the mass ratio of CDI to DMSO is 10.8:100), stir at room temperature until completely dissolved, then quickly add the agarose solution and stir at room temperature for 2 h. Add 10 mL 98% ethylenediamine to the resulting solution and stir in the dark for 24 h. Dialyze for 72 h and freeze dry for 48 h to obtain AG-NH2.

[0023] (2) 0.1 g AG-NH2 and 5 g ionic liquid [EMIM][OAc] were heated at 110 ℃ and stirred for 1-2 min to obtain a clear and transparent liquid (i.e., the mass ratio of AG-NH2 to [EMIM][OAc] is 2:100); after cooling to room temperature, 90.4 µL of 50 wt% glutaraldehyde aqueous solution (i.e., the mass ratio of glutaraldehyde to AG-NH2 is 1:2) was added under vortex action, and after thorough mixing and standing, glutaraldehyde self-healing ionic gel was obtained. The AG-NH2 Schiff base self-healing ionogel described in this embodiment exhibits the following characteristics: macroscopically, it completely separates into two pieces under external force, and upon reassembly, significant healing occurs within 5 seconds, with the healed gel exhibiting high strength; microscopically, under 20× magnification using an optical microscope, the damaged ionogel is observed to completely heal within 2 minutes; the damaged gel, when squeezed out using a No. 23 syringe, can form a gel with an intact shape, demonstrating excellent injectability and good tensile strength; the glutaraldehyde self-healing ionogel can adhere to various materials, such as silicone, iron, glass, paper, skin, and wood, exhibiting good adhesion.

[0024] Example 5 The difference from Example 4 is that (2) the operation steps are as follows: 0.15 g of AG-NH2 and 5 g of ionic liquid [EMIM][OAc] are weighed, without adding glutaraldehyde, heated at 110 °C for 30 min, and cooled to room temperature to obtain a self-healing pure ionic gel without glutaraldehyde. The macroscopic experimental effects, properties and adhesion are similar to those of Example 4. Microscopically, it was observed under a 20× magnification optical microscope that the damaged ionic gel could be completely healed within 40 min.

[0025] Example 6 The difference from Example 4 is that (2) the operation steps are as follows: 0.1 g of AG-NH2 is heated and dissolved in 5 g of ionic liquid [EMIM][OAc] at 110 °C (i.e., the mass ratio of AG-NH2 to ionic liquid [EMIM][OAc] is 2:100), and the added aldehyde molecule is 0.4 mL of pyromellitic methyl ether methanol solution (i.e., the mass ratio of pyromellitic methyl ether to AG-NH2 is 1:10). The obtained AG-NH2 Schiff base self-healing ionic gel: macroscopically, the two broken ionic gels showed obvious healing after contact for 3 min, and the healed gel had a certain strength under gravity; the other properties of the pyromellitic methyl ether crosslinked ionic gel are similar to those of the AG-NH2 Schiff base self-healing ionic gel in Example 4.

[0026] Example 7 The difference from Example 4 is that in (2), the ionic liquid [EMIM][OAc] is replaced with 5 g of the eutectic solvent ChCl / LA, and the other steps are the same as in Example 4. The AG-NH2 Schiff base self-healing eutectic gel described in this example has a significantly longer self-healing time than hydrogels and ionic gels. Since this type of eutectic gel is relatively hard and brittle, it is basically not injectable; it has good adhesion to materials such as plastics, but poor adhesion to the skin.

[0027] Comparative Example 1 The difference from Example 1 is that no aldehyde molecule is added in (2), while the other steps are the same as in Example 1. In the case described in this comparative example, since no aldehyde molecule is added, the network structure formed by AG-NH2 through weak intermolecular interactions cannot lock in the solvent water, so a hydrogel cannot be formed.

[0028] Comparative Example 2 The difference from Example 1 is that: (2) 0.75 g of AG-NH2 was added (i.e., the mass ratio of AG-NH2 to water was 1.5:100), and 0.18 or 0.9 mL of 50 wt% glutaraldehyde aqueous solution was added (i.e., the mass ratio of glutaraldehyde to AG-NH2 was 1:10 or 1:2). All other steps were the same as in Example 1. In the case described in this comparative example, the hydrogel with a mass ratio of glutaraldehyde to AG-NH2 of 1:10 has good self-healing properties. It forms a gel 2 min after the addition of glutaraldehyde. This hydrogel has a certain degree of viscoelasticity. When divided into two pieces and placed together, it immediately heals into a whole piece. The hydrogel with a mass ratio of glutaraldehyde to AG-NH2 of 1:2 has excellent self-healing properties. It forms a gel immediately after the addition of glutaraldehyde. This hydrogel has a certain degree of viscoelasticity. When cut into two pieces and placed together, it immediately heals into a whole piece. It can be picked up with tweezers without being separated.

[0029] Comparative Example 3 The difference from Example 5 is that: (2) the ionic liquid used is 1-butyl-3-methylimidazolium acetate [BMIM][OAc], 1-hexyl-3-methylimidazolium acetate [HMIM][OAc], 1-butyl-3-methylimidazolium chloride [BMIM][Cl], 1-hexyl-3-methylimidazolium chloride [HMIM][Cl], 1-butyl-3-methylimidazolium tetrafluoroborate [BMIM][BF4], or 1-hexyl-3-methylimidazolium tetrafluoroborate. Ionic gels of different concentrations were prepared using one of the following salts: [HMIM][BF4], 1-butyl-3-methylimidazolium hexafluorophosphate [BMIM][PF6], 1-hexyl-3-methylimidazolium hexafluorophosphate [HMIM][PF6], 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide [BMIM][TFSI], 1-hexyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide [HMIM][TFSI], or ethylammonium nitrate (EAN). In this comparative example, only the ionic liquids [BMIM][OAc], [HMIM][OAc], [BMIM][Cl], and [HMIM][Cl] could form AG-NH2 self-healing ionic gels. The self-healing properties and viscoelasticity of the formed ionic gels differed. Comprehensive analysis showed that the self-healing ionic gel prepared in [EMIM][OAc] exhibited superior performance.

[0030] Comparative Example 4 The difference from Example 5 is that: (2) AG-NH2 was used instead of agarose AG to prepare gels of different concentrations in different solvents, and the following solvents were also expanded: deionized water, 1-butyl-3-methylimidazolium acetate [BMIM][OAc], 1-hexyl-3-methylimidazolium acetate [HMIM][OAc], 1-butyl-3-methylimidazolium chloride [BMIM][Cl], 1-hexyl-3-methylimidazolium chloride [HMIM][Cl], 1-butyl-3-methylimidazolium tetrafluoroboric acid The salts included were [BMIM][BF4], 1-hexyl-3-methylimidazolium tetrafluoroborate [HMIM][BF4], 1-butyl-3-methylimidazolium hexafluorophosphate [BMIM][PF6], 1-hexyl-3-methylimidazolium hexafluorophosphate [HMIM][PF6], 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide [BMIM][TFSI], 1-hexyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide [HMIM][TFSI], and ethylammonium nitrate (EAN). In the cases described in this comparative example, unmodified AG only formed gels in water, ionic liquids [BMIM][Cl], and [HMIM][Cl], and failed to gel in other conditions. This indicates that the amino-functionalized agarose, i.e., AG-NH2, exhibits stronger gelling ability in ionic liquids.

[0031] Comparative Example 5 The difference from Example 4 is that (2) 0.27-0.36 mL of 50 wt% glutaraldehyde aqueous solution was added (i.e., the mass ratio of glutaraldehyde to AG-NH2 is 1.5-2:1). The AG-NH2 Schiff base self-healing ion gel described in this comparative example still has self-healing properties, but due to the gradual increase in the proportion of glutaraldehyde, more Schiff base cross-linking bonds are generated, resulting in increased brittleness and decreased viscosity of the prepared ion gel. The adhesion of the ion gel to various materials is relatively weak.

[0032] Comparative Example 6 The difference from Example 7 is that (2) the eutectic solvent ChCl / LA can be replaced with choline chloride / glycolic acid ChCl / GlyAc, choline chloride / acetic acid ChCl / Ac, choline chloride / glycerol ChCl / Gly, and choline chloride / ethylene glycol ChCl / EG in a molar ratio of 1:2, respectively. All other steps are the same as in Example 7. In the case described in this comparative example, only ChCl / GlyAc can form a gel. Its self-healing properties and adhesion are similar to those of the gel formed by ChCl / LA, but its gel-forming properties are somewhat inferior.

[0033] Comparative Example 7 The difference from Example 7 is that no aldehyde molecule is added in (2), while the other steps are the same as in Example 7. In the case described in this comparative example, AG-NH2 cannot form a gel in ChCl / LA because no aldehyde molecule is added.

[0034] Comparative Example 8 The difference from Examples 1, 4 and 7 is that in (2), a small aldehyde molecule was added to introduce vanillin with good biocompatibility, while the other steps were the same as in Examples 1, 4 and 7. In the case described in this comparative example, the addition of the small aldehyde molecule vanillin did not form a gel. This is because the aldehyde group of vanillin has low activity and is difficult to directly form a Schiff base with AG-NH2 and form a three-dimensional network structure to lock in the solvent.

[0035] Experimental example: Experimental Example 1: Synthesis of AG-NH2 Figure 1 In the AG-NH2 synthesis step of this invention, ethylenediamine is modified onto AG using CDI catalysis under conditions of room temperature and DMSO as solvent.

[0036] Characterization of AG-NH2 in Experimental Example 2 Figure 2 A, 2B, and 2C are the basic characterizations of AG and AG-NH2 in this invention, derived from... Figure 2A Fourier transform infrared spectral curve shows that, by comparing the infrared curves of AG and AG-NH2 at 1715, 1265, and 770 cm⁻¹, -1 The changes confirmed the successful modification of the amino group onto the AG molecule. The crystal structures of agarose before and after amino modification were analyzed using X-ray diffraction (XRD). Figure 2 The XRD patterns of B show that the two types of agarose exhibit different diffraction peaks within the diffraction angle range of 5-50° (2θ). Unmodified agarose shows a relatively sharp and strong peak at 2θ = 19°, along with two less noticeable small peaks at 27° and 42°, indicating the amorphous nature of the agarose molecule. The amino-modified agarose shows a significant decrease in diffraction peak intensity and a larger peak width, with 2θ increasing to 23°, and almost no other diffraction peaks are observed. These results indicate that modifying agarose molecules with amino groups significantly alters the hydrogen bonding within the polysaccharide molecule, further enhancing its amorphous state. Figure 2 The X-ray photoelectron spectroscopy (XPS) curve of C shows that after fitting, two peaks are obtained at 399.1 eV and 399.8 eV, corresponding to -CO-NH and -CH2-NH2, respectively, indicating that ethylenediamine was successfully grafted onto the agarose molecule.

[0037] Experimental Example 3: Light Transmittance Test Figure 3 A represents the transmittance variation curves of glutaraldehyde self-healing hydrogel, glutaraldehyde self-healing ionogel, self-healing pure ionogel, and glutaraldehyde self-healing eutectic gel in Examples 1, 4, 5, and 7 of this invention at 400-800 nm. Figure 3 As shown in A, the self-healing pure ion gel has the best light transmittance, and the glutaraldehyde self-healing ion gel also has excellent light transmittance. Both have a light transmittance of up to 95% above 600nm. The light transmittance of glutaraldehyde self-healing hydrogel and glutaraldehyde self-healing eutectic gel is relatively poor.

[0038] Experimental Example 4: Thermodynamic Performance Testing Figure 3 B shows the TGA test curves of glutaraldehyde self-healing hydrogel, ionic liquid [EMIM][OAc], glutaraldehyde self-healing ionic gel, self-healing pure ionic gel, eutectic solvent ChCl / LA, and glutaraldehyde self-healing eutectic gel in Examples 1, 4, 5, and 7 of this invention. The TGA test curves show that the glutaraldehyde self-healing hydrogel experiences weight loss from the start of heating and completely decomposes before 100 °C; the decomposition temperature of the ionic liquid [EMIM][OAc] is 213 °C; the decomposition temperature of the self-healing pure ionic gel is 215 °C; the decomposition temperature of the glutaraldehyde self-healing ionic gel is 219 °C; the decomposition temperature of the eutectic solvent is 166 °C; and the decomposition temperature of the glutaraldehyde self-healing eutectic gel is 166 °C. Figure 3C and Figure 3 D represents the DSC test curves of glutaraldehyde self-healing hydrogel, ionic liquid [EMIM][OAc], glutaraldehyde self-healing ionic gel, self-healing pure ionic gel, eutectic solvent ChCl / LA, and glutaraldehyde self-healing eutectic gel in Figures 1, 4, 5, and 7. As shown in the figure, the glutaraldehyde self-healing hydrogel did not exhibit an endothermic peak in the range of 20-70 °C. Not only ionic liquids and eutectic solvents, but gels prepared from these two types of solvents also showed good low-temperature resistance.

[0039] Experimental Example 5: Adhesion Performance Test Figure 4 Examples 1-6 of this invention present adhesion test examples of glutaraldehyde hydrogel, acetone aldehyde hydrogel, trimesoaldehyde hydrogel, glutaraldehyde ionomer, pure ionomer, and trimesoaldehyde ionomer. As shown in the figures, the hydrogels and ionomers exhibit good adhesion to various materials, such as skin, silicone, glass, paper, and wood. This is significant for the subsequent application of the gel as an electrode patch to ensure good adhesion to the skin.

[0040] Experimental Example 6: Self-Healing Performance Test Figure 5 A, 5B, and 5C represent the macroscopic self-healing test, microscopic self-healing observation, and injectability test of the glutaraldehyde hydrogel in Example 1 of this invention, respectively. Under macroscopic conditions, the damaged gel showed obvious healing within 10 seconds and had a certain strength after healing. Under the microscope, the incision was basically healed within 15 minutes. The damaged gel could be squeezed out with a No. 23 syringe to form a gel with an intact shape, demonstrating excellent injectability. Figure 6 A and 6B represent the macroscopic self-healing test and injectability test of the acetone aldehyde hydrogel in Example 2 of this invention, respectively. Under macroscopic conditions, the damaged gel can show obvious healing within 10 seconds and has a certain strength after healing. The damaged gel can be squeezed out with a No. 23 syringe to form a gel with a complete shape, showing excellent injectability. Figure 7 A and Figure 7 B represents the macroscopic self-healing test and injectability test of the pyromellitic trimethylolpropionic acid hydrogel in Example 3 of this invention. Under macroscopic conditions, the damaged gel showed obvious healing within 3 minutes, and the healed sample had a certain strength under gravity. The damaged gel could be squeezed out with a No. 23 syringe to form a gel with an intact shape, showing excellent injectability. Figure 8A, 8B, and 8C represent the macroscopic self-healing test, microscopic self-healing observation, and injectability test of the glutaraldehyde ion gel in Example 4 of this invention, respectively. Under macroscopic conditions, the damaged gel showed obvious healing within 5 seconds and had a certain strength after healing. Under the microscope, the incision basically healed within 2 minutes. The damaged gel could be squeezed out with a No. 23 syringe to form a gel with an intact shape, demonstrating excellent injectability. Figure 9 A, 9B, and 9C represent the macroscopic self-healing test, microscopic self-healing observation, and injectability test of the pure ion gel in Example 5 of this invention, respectively. Under macroscopic conditions, the damaged gel showed obvious healing within 10 seconds and had a certain strength after healing. Under the microscope, the incision was basically healed within 40 minutes. The damaged gel could be squeezed out with a No. 23 syringe to form a gel with an intact shape, demonstrating excellent injectability. Figure 10 A and 10B are respectively the macroscopic self-healing test and injectability test of the trimethylol ionomer gel in Example 6 of the present invention. Under macroscopic conditions, the damaged gel can show obvious healing within 3 minutes, and the healed gel has a certain strength under gravity. The damaged gel can be squeezed out with a No. 23 syringe to form a gel with a complete shape, showing excellent injectability.

[0041] Test Example 7: Proof of Self-Healing Figure 11 A and Figure 11 B shows the infrared absorption curves of the glutaraldehyde hydrogel from Example 1 and the glutaraldehyde ionogel from Example 4. As can be seen from the figure, compared to the infrared curve of AG-NH2, the gels show absorption curves at approximately 1638 and 1650 cm⁻¹. -1 The presence of imine bond infrared absorption indicates the existence of Schiff base dynamic equilibrium in the glutaraldehyde crosslinked gel network. Infrared curves show that the self-healing gel forms reversible imine bonds through Schiff base reactions to impart self-healing properties, while other non-covalent interactions also promote self-healing. Figure 11 C represents the steady-state shear results of the glutaraldehyde self-healing hydrogel in Example 1. The downward and upward viscosity curves are almost identical, indicating that the glutaraldehyde hydrogel has good thixotropy and can recover its network structure more quickly after mechanical damage. Strong thixotropy also demonstrates the good self-healing properties of the glutaraldehyde hydrogel, as its network structure can be rebuilt in a short time using dynamically reversible imine and hydrogen bonds after being damaged. Figure 11 D represents the continuous step strain scan results of the glutaraldehyde self-healing ionogel in Example 4. When large and small stresses are applied alternately to the glutaraldehyde ionogel, the modulus values ​​under the same stress are not significantly different, indicating that the damaged network structure can recover rapidly in a short time, which also confirms the good self-healing properties of the glutaraldehyde ionogel.

[0042] Experimental Example 8: Rheological Properties Figure 12 A shows a stress scan comparison of glutaraldehyde self-healing hydrogel, glutaraldehyde self-healing ionogel, and glutaraldehyde self-healing eutectic gel under the same AG-NH2 concentration and the same glutaraldehyde to AG-NH2 mass ratio in Comparative Examples 2, 4, and 7. As can be seen from the figure, the glutaraldehyde eutectic gel has the highest mechanical strength, followed by the glutaraldehyde self-healing hydrogel, while the glutaraldehyde self-healing ionogel has the lowest mechanical strength.

[0043] Experimental Example 9: Conductivity and Interfacial Impedance Testing Figure 12 B shows the conductivity test curves of glutaraldehyde self-healing hydrogel, ionic liquid, glutaraldehyde self-healing ionic gel and self-healing pure ionic gel in Examples 1, 4 and 5 of this invention. As can be seen from the figure, the hydrogel has the lowest conductivity, while the ionic gel has a superior conductivity. This is beneficial for using ionic gel as an electrode patch to collect and monitor human electrophysiological signals. Figure 12 C represents the interfacial impedance curves of glutaraldehyde self-healing hydrogel, glutaraldehyde self-healing ionogel, and self-healing pure ionogel on human skin in Examples 1, 4, and 5 of this invention. As shown in the figure, the hydrogel and ionogel have lower interfacial impedance than the commercial electrode. The lower the interfacial impedance, the more beneficial it is for the measurement of electrophysiological signals.

[0044] Experimental Example 10: Electrocardiogram Test Figure 13 Figures A and 13B show the ECG signal monitoring results of glutaraldehyde self-healing hydrogel, glutaraldehyde self-healing ionogel, and self-healing pure ionogel compared with commercial Ag / AgCl electrodes on days 1 and 7 in Examples 1, 4, and 5 of this invention. The comparison shows that the hydrogel and ionogel electrodes prepared in this invention are superior to commercial electrodes in ECG monitoring, exhibiting low baseline noise. After seven days, the signal-to-noise ratio of commercial electrodes decreased significantly, and the baseline became thicker, while the baselines of the two types of ionogel electrodes remained essentially unchanged, indicating that the two types of ionogel electrodes prepared still possess excellent ECG signal monitoring capabilities after prolonged placement. Figure 14 Figures A and 14B show the ECG signal monitoring results of the glutaraldehyde self-healing ion gel and the commercial Ag / AgCl electrode in Example 4 of this invention after repeated application and use. As can be seen from the figures, the glutaraldehyde ion gel still maintains excellent low-noise signal monitoring performance after up to 20 repeated applications and use; the commercial electrode showed a significant increase in ECG signal noise after multiple uses. This indicates that the gel electrode in this invention is more outstanding in its ability to maintain a low signal-to-noise ratio during repeated use of ECG signals, which is in line with the concept of green environmental protection.

[0045] Experimental Example 11: Electromyography (EMG) Test Figure 15A represents the resting / vibration electromyography (EMG) signal of the glutaraldehyde self-healing ion gel in Example 4. The signal intensity monitored by the glutaraldehyde ion gel under resting and vibration conditions is similar to that of the commercial Ag / AgCl electrode. However, the signal baseline of the glutaraldehyde ion gel electrode is finer and the signal-to-noise ratio is higher, indicating that the glutaraldehyde ion gel electrode has higher accuracy and precision in monitoring EMG signals compared to the commercial electrode. Figure 15 Figures B and 15C show the electromyography (EMG) signal monitoring results of the self-healing pure ion gel electrode in Example 5 under resting / vibration and different grip forces. As can be seen from the figures, the monitoring signal intensity of the pure ion gel electrode under resting / vibration and different grip forces is higher than that of the commercial Ag / AgCl electrode. However, the baseline of the signal tested by the pure ion gel electrode is finer and the signal-to-noise ratio is higher, indicating that the pure ion gel electrode has higher accuracy and precision in EMG signal monitoring compared to the commercial electrode. In the EMG signal test under different grip forces, the pure ion gel electrode has a more obvious distinction in the magnitude of applied force compared to the commercial electrode.

Claims

1. The application of amino-functionalized agarose self-healing gel in flexible epidermal electrodes, characterized in that, The amino-functionalized agarose self-healing gel refers to any one of the following: AG-NH2 Schiff base self-healing hydrogel, AG-NH2 Schiff base self-healing ionogel, and AG-NH2 self-healing ionogel. Among them, the AG-NH2 Schiff base self-healing hydrogel is prepared using AG-NH2, aldehyde small molecules, and deionized water as the main raw materials; the mass ratio of AG-NH2 to deionized water is 2:

100. When the aldehyde molecule is a 50 wt% aqueous solution of glutaraldehyde, the mass ratio of the aldehyde molecule to AG-NH2 is 2:

100. When the aldehyde small molecule is a 40 wt% acetone aldehyde aqueous solution, the mass ratio of the aldehyde small molecule to AG-NH2 is 5:100 or 1:1; When the aldehyde molecule is pyromellitic methyl ether, the mass ratio of the aldehyde molecule to AG-NH2 is 5:

100. The AG-NH2 Schiff base self-healing ionic gel was prepared using AG-NH2, aldehyde small molecules, and ionic liquid 1-ethyl-3-methylimidazolium acetate [EMIM][OAc] as the main raw materials; the mass ratio of AG-NH2 to ionic liquid 1-ethyl-3-methylimidazolium acetate [EMIM][OAc] was 2:

100. When the aldehyde small molecule is a 50 wt% glutaraldehyde aqueous solution, the mass ratio of the aldehyde small molecule to AG-NH2 is 1:2; When the aldehyde molecule is a methanol solution of pyromellitic aldehyde, the mass ratio of the aldehyde molecule to AG-NH2 is 1:

10. The AG-NH2 self-healing ionic gel was prepared using AG-NH2 and the ionic liquid 1-ethyl-3-methylimidazolium acetate [EMIM][OAc] as the main raw materials; the mass ratio of AG-NH2 to the ionic liquid 1-ethyl-3-methylimidazolium acetate [EMIM][OAc] was 3:

100.

2. The application as described in claim 1, characterized in that, The flexible epidermal electrode is used to monitor electrophysiological signals.

3. The application as described in claim 1, characterized in that, The electrodes are: a skin electrode for monitoring electrocardiogram signals and a skin electrode for monitoring electromyogram signals.

4. The application as described in claim 1, characterized in that, The synthesis method of AG-NH2 is as follows: (1) Heat and stir agarose AG to dissolve it in dimethyl sulfoxide (DMSO); the mass ratio of agarose to DMSO is 1.2:

100. (2) Under N2 atmosphere, N,N-carbonyldiimidazole CDI was added to dimethyl sulfoxide DMSO and stirred at room temperature until N,N-carbonyldiimidazole was completely dissolved; the mass ratio of N,N-carbonyldiimidazole CDI to dimethyl sulfoxide DMSO was 10.8:

100. (3) Take the material dissolved in (1) and quickly add it to the solution dissolved in (2). Stir at room temperature for 2 h. Then add excess ethylenediamine and stir in the dark for 24 h. Dialyze and freeze dry to obtain amino-modified agarose AG-NH2. During dialysis, the molecular weight cutoff of the dialysis bag is 8000-14000 Da. Dialyze for 72 h and freeze dry for 48 h.

5. The application as described in claim 1, characterized in that, When the self-healing gel is an AG-NH2 Schiff base self-healing hydrogel, its preparation method is as follows: S1-1: Add AG-NH2 to deionized water and heat to 70 ℃, stir for 30 min to dissolve it, and cool to room temperature to obtain solution I; S1-2: Under room temperature vortex conditions, a 50 wt% aqueous solution of glutaraldehyde and deionized water are mixed to obtain solution II; Alternatively, mix 40 wt% acetone aldehyde aqueous solution with deionized water to obtain solution II; Alternatively, pyromellitic aldehyde and methanol can be mixed to obtain solution II; S1-3: Under room temperature vortex conditions, solution II is added dropwise to solution I to mix the two, thus obtaining AG-NH2 Schiff base self-healing hydrogel.

6. The application as described in claim 1, characterized in that, When the self-healing gel is an AG-NH2 Schiff base self-healing ionic gel, its preparation method is as follows: S2-1: Heat and stir at 110 °C for 1-2 min to dissolve AG-NH2 in the ionic liquid 1-ethyl-3-methylimidazolium acetate [EMIM][OAc] to obtain a clear and transparent liquid, and cool to room temperature; S2-2: Under vortex action, add 50 wt% glutaraldehyde aqueous solution or trimesaldehyde methanol solution to the material cooled in S2-1, mix thoroughly and let stand to obtain AG-NH2 Schiff base self-healing ionogel.

7. The application as described in claim 1, characterized in that, When the self-healing gel is an AG-NH2 self-healing ionic gel, its preparation method is as follows: AG-NH2 was dissolved in the ionic liquid 1-ethyl-3-methylimidazolium acetate [EMIM][OAc] by heating and stirring at 110 °C for 30 min to obtain a clear and transparent liquid. The solution was then cooled to room temperature to obtain AG-NH2 self-healing ionic gel.

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