Hydrogel substrate material as well as preparation method and application thereof

Abstract

The invention provides a hydrogel substrate material and a preparation method and application thereof.The hydrogel substrate material is composed of a hydrogel matrix and functional filler dispersed in the hydrogel matrix, and the hydrogel matrix is composed of sulfobetaine, methylene bisacrylamide, ammonium persulfate and tetramethylethylenediamine; the functional filler is prepared from zinc sulfate, carboxylated cellulose nanofibers, platinum nanoparticles and glucolase; the preparation method comprises the following steps: respectively preparing a hydrogel precursor solution and a glucolase solution, mixing the hydrogel precursor solution and the glucolase solution, and curing in a water bath kettle, the adopted preparation method is simple, convenient and efficient, the hydrogel substrate material is applied to a biosensor substrate, and the biosensor substrate has high conductivity, high mechanical strength and good biocompatibility, and is suitable for large-scale production. The method has a wide application prospect in the field of biosensor substrate materials.

Description

Technical Field

[0001] The invention relates to the technical field of functional polymer materials, in particular to the technical field of a hydrogel substrate material and a preparation method and application thereof. Background Art

[0002] Diabetes is a serious disease that threatens human health and life worldwide. Its long-term management depends on real-time monitoring of blood glucose levels. Electrochemical glucose enzyme sensors have become an important part of current blood glucose monitoring equipment due to their high sensitivity, rapid response and portability. However, traditional hydrogels as sensor substrates have problems such as poor conductivity and low mechanical strength, which seriously affect the performance and application of sensors.

[0003] Based on this, in order to improve the stability and sensitivity of biosensors, it is urgent to develop new hydrogel materials with high conductivity and excellent mechanical properties to optimize the application effect of electrochemical biosensors. Summary of the invention

[0004] The technical problem to be solved by the present invention is to provide a hydrogel base material.

[0005] Another technical problem to be solved by the present invention is to provide a method for preparing the above hydrogel substrate material.

[0006] Another technical problem to be solved by the present invention is to provide application of the above hydrogel base material.

[0007] The technical solution adopted by the present invention is:

[0008] A hydrogel base material consists of a hydrogel matrix and a functional filler dispersed in the hydrogel matrix, wherein the hydrogel matrix consists of sulfobetaine, methylenebisacrylamide, ammonium persulfate and tetramethylethylenediamine, and the ratio of sulfobetaine:methylenebisacrylamide:ammonium persulfate:tetramethylethylenediamine is (0.2-0.5) g:(5-20) mg:(5-20) mg:(3-20) μl; the functional filler consists of zinc sulfate, carboxylated cellulose nanofibers, platinum nanoparticles and glucose enzyme, and the mass ratio of the hydrogel matrix to the zinc sulfate, carboxylated cellulose nanofibers, platinum nanoparticles and glucose enzyme is (0.2-0.5) g:(1-12) mg:(20-60) mg:(5-100) mg:(5-100) mg.

[0009] In the hydrogel base material, sulfobetaine is a zwitterionic gel monomer, methylenebisacrylamide is a crosslinking agent, ammonium persulfate is an initiator, and tetramethylethylenediamine is a catalyst. The proportions of each mixture can be increased or decreased in proportion.

[0010] Preferably, in the above hydrogel base material, the glucose enzyme is glucose oxidase, glucose dehydrogenase or catalase.

[0011] Preferably, in the above hydrogel base material, the ratio of sulfobetaine:methylenebisacrylamide:ammonium persulfate:tetramethylethylenediamine=0.4g:10mg:10mg:6μl.

[0012] Preferably, in the above-mentioned hydrogel base material, the mass ratio of the hydrogel matrix to zinc sulfate, carboxylated cellulose nanofibers, platinum nanoparticles, and glucose enzyme is 0.4g:8mg:30mg:10mg:50mg.

[0013] The preparation method of the hydrogel substrate material comprises the following specific steps:

[0014] (1) mixing sulfobetaine, carboxylated cellulose nanofibers, zinc sulfate, methylenebisacrylamide, ammonium persulfate and PBS buffer, then adding platinum nanoparticles and tetramethylethylenediamine, and stirring to obtain a hydrogel precursor solution;

[0015] (2) adding the lyophilized glucose enzyme powder to PBS buffer, mixing and stirring to obtain a glucose enzyme solution;

[0016] (3) The hydrogel precursor solution is mixed with the glucose enzyme solution and then solidified in a water bath to obtain the hydrogel.

[0017] Preferably, in the preparation method of the above-mentioned hydrogel base material, the mass volume ratio of sulfobetaine, carboxylated cellulose nanofibers, zinc sulfate, methylenebisacrylamide, ammonium persulfate, PBS buffer, platinum nanoparticles and tetramethylethylenediamine in step (1) is (0.2-0.5) g: (20-60) mg: (1-12) mg: (5-20) mg: (5-20) mg: (0.1-1) ml: (5-100) mg: (3-20) μl.

[0018] Preferably, in the method for preparing the hydrogel substrate material, the glucose enzyme freeze-dried powder in step (2) is glucose oxidase freeze-dried powder, glucose dehydrogenase freeze-dried powder or catalase freeze-dried powder.

[0019] Preferably, in the method for preparing the hydrogel base material, the volume ratio of the hydrogel precursor solution to the glucose enzyme solution in step (3) is 1:1.

[0020] Preferably, in the method for preparing the hydrogel base material, the curing environment in step (3) is at 30° C. to 37° C.

[0021] The above hydrogel substrate material is used as a flexible sensor substrate.

[0022] Application of the above hydrogel substrate material in the preparation of diabetes detection equipment.

[0023] Preferably, in the application of the above hydrogel substrate material, the diabetes detection device is an electrochemical glucose enzyme sensor.

[0024] The beneficial effects of the present invention are:

[0025] The hydrogel substrate material is constructed using zwitterionic gel monomer sulfobetaine, and the electron mobility is improved by introducing platinum nanoparticles; a stable ion channel is constructed inside the material by adding zinc sulfate, which effectively regulates and improves the conductivity of the hydrogel, and the synergistic effect of each component makes the material have good biocompatibility and improves its electrical signal strength; the uniformity and density of the internal structure of the hydrogel are enhanced by the physical entanglement of carboxylated cellulose nanofibers, thereby enhancing the mechanical properties of the hydrogel and ensuring that the structure remains intact and stable during manufacturing, transportation and daily use; glucose enzyme is used to catalyze electrochemical reactions to enhance its detection performance; the preparation method adopted is simple and efficient, and the hydrogel substrate material is applied to the biosensor substrate, which has high conductivity, high mechanical strength and good biocompatibility, and has broad application prospects in the field of biosensor substrate materials. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 This is a schematic diagram of the components of the hydrogel base material of the present invention.

[0027] Figure 2 This is a comparison diagram of the tensile stress-strain of the hydrogel base material of the present invention and the unmodified hydrogel.

[0028] Figure 3 This is a comparison chart of the electrical conductivity of the hydrogel base material of the present invention and the unmodified hydrogel.

[0029] Figure 4 This is a comparison chart between the blood glucose prediction value obtained by the electrochemical glucose enzyme sensor and the blood glucose reference value. DETAILED DESCRIPTION

[0030] In order to enable those skilled in the art to better understand the technical solution of the present invention, the technical solution of the present invention is further described in detail below in conjunction with the accompanying drawings and specific implementation methods.

[0031] Example 1

[0032] A hydrogel base material, comprising a hydrogel matrix and a functional filler dispersed in the hydrogel matrix, wherein the hydrogel matrix comprises sulfobetaine, methylenebisacrylamide, ammonium persulfate and tetramethylethylenediamine, and the functional filler comprises zinc sulfate, carboxylated cellulose nanofibers, platinum nanoparticles and glucose enzyme. The preparation method thereof is as follows:

[0033] (1) 0.4 g of sulfobetaine, 500 μL of carboxylated cellulose nanofiber suspension (6 wt%), 8 mg of zinc sulfate, 10 mg of methylenebisacrylamide, 10 mg of ammonium persulfate, and 100 μL of PBS buffer were mixed, and then 100 μL of platinum nanoparticle solution (100 mg / ml) and 6 μL of tetramethylethylenediamine were added, and the mixture was stirred to obtain a hydrogel precursor solution;

[0034] (2) adding 50 mg of glucose oxidase freeze-dried powder to 500 μl of PBS buffer and stirring to obtain a glucose oxidase solution with a concentration of 100 mg / ml;

[0035] (3) Take 100 μl of the above hydrogel precursor solution and glucose oxidase solution, mix them and solidify them in a 37° C. water bath for 24 h to obtain a hydrogel base material. The structure of the hydrogel base material is as follows: Figure 1 shown.

[0036] Example 2

[0037] A hydrogel base material, comprising a hydrogel matrix and a functional filler dispersed in the hydrogel matrix, wherein the hydrogel matrix comprises sulfobetaine, methylenebisacrylamide, ammonium persulfate and tetramethylethylenediamine, and the functional filler comprises zinc sulfate, carboxylated cellulose nanofibers, platinum nanoparticles and glucose enzyme. The preparation method thereof is as follows:

[0038] (1) 0.4 g of sulfobetaine, 500 μL of carboxylated cellulose nanofiber suspension (6 wt%), 8 mg of zinc sulfate, 10 mg of methylenebisacrylamide, 10 mg of ammonium persulfate and 100 μL of PBS buffer were mixed, and then 100 μL of platinum nanoparticle solution (100 mg / ml) and 6 μL of tetramethylethylenediamine were added and stirred to obtain a hydrogel precursor solution;

[0039] (2) adding 10 mg of glucose dehydrogenase lyophilized powder to 1 ml of PBS buffer and mixing and stirring to obtain a glucose oxidase solution with a concentration of 10 mg / ml;

[0040] (3) Mix 100 μl of the above hydrogel precursor solution and glucose dehydrogenase solution and cure them in a 37° C. water bath for 24 h to obtain a hydrogel base material.

[0041] Example 3

[0042] A hydrogel base material, comprising a hydrogel matrix and a functional filler dispersed in the hydrogel matrix, wherein the hydrogel matrix comprises sulfobetaine, methylenebisacrylamide, ammonium persulfate and tetramethylethylenediamine, and the functional filler comprises zinc sulfate, carboxylated cellulose nanofibers, platinum nanoparticles and glucose enzyme. The preparation method thereof is as follows:

[0043] (1) 0.2 g of sulfobetaine, 333 μL of carboxylated cellulose nanofiber suspension (6 wt%), 1 mg of zinc sulfate, 5 mg of methylenebisacrylamide, 5 mg of ammonium persulfate, and 100 μL of PBS buffer were mixed, and then 50 μL of platinum nanoparticle solution (100 mg / ml) and 3 μL of tetramethylethylenediamine were added and stirred to obtain a hydrogel precursor solution;

[0044] (2) adding 5 mg of glucose oxidase lyophilized powder to 500 μl of PBS buffer and mixing and stirring to obtain a glucose oxidase solution with a concentration of 10 mg / ml;

[0045] (3) Mix 100 μl of the above hydrogel precursor solution and glucose dehydrogenase solution and cure them in a 37° C. water bath for 24 h to obtain a hydrogel base material.

[0046] Example 4

[0047] A hydrogel base material, comprising a hydrogel matrix and a functional filler dispersed in the hydrogel matrix, wherein the hydrogel matrix comprises sulfobetaine, methylenebisacrylamide, ammonium persulfate and tetramethylethylenediamine, and the functional filler comprises zinc sulfate, carboxylated cellulose nanofibers, platinum nanoparticles and glucose enzyme. The preparation method thereof is as follows:

[0048] (1) 0.5 g of sulfobetaine, 1 mL of carboxylated cellulose nanofiber suspension (6 wt%), 12 mg of zinc sulfate, 60 mg of methylenebisacrylamide, 60 mg of ammonium persulfate, and 1 ml of PBS buffer were mixed, and then 1 ml of platinum nanoparticle solution (100 mg / ml) and 20 μl of tetramethylethylenediamine were added and stirred to obtain a hydrogel precursor solution;

[0049] (2) adding 100 mg of glucose oxidase lyophilized powder to 500 μl of PBS buffer and mixing and stirring to obtain a glucose oxidase solution with a concentration of 200 mg / ml;

[0050] (3) Mix 100 μl of the above hydrogel precursor solution and glucose dehydrogenase solution and cure them in a 37° C. water bath for 24 h to obtain a hydrogel base material.

[0051] Example 5

[0052] The mechanical properties of the hydrogel substrate material described in Example 1 were verified by the following method:

[0053] (1) The hydrogel base material and the unmodified sulfobetaine hydrogel were solidified into strip samples respectively.

[0054] (2) Fix the hydrogel sample with a clamp at the initial position of the stretching platform of the flexible electronics in-situ testing system and stretch it outward until the sample breaks.

[0055] (3) Record the changes in the amount of stretch and tensile stress of the sample during the stretching process. The results are as follows: Figure 2 shown.

[0056] Depend on Figure 2 It can be seen that the hydrogel substrate material of the present invention can withstand greater tensile stress than unmodified hydrogel.

[0057] Example 6

[0058] The specific method of the test for the conductive performance of the hydrogel substrate material described in Example 1 is as follows:

[0059] (1) The hydrogel substrate material and the unmodified sulfobetaine hydrogel were solidified into rectangular samples respectively.

[0060] (2) Fix the hydrogel sample in the flexible electronics in situ testing system and measure the resistance of the hydrogel sample.

[0061] (3) The conductivity of the sample is calculated by the hydrogel resistance. The results are as follows: Figure 3 shown.

[0062] Depend on Figure 3 It can be seen that the conductivity of the hydrogel base material of the present invention is 2.35 times that of the unmodified hydrogel.

[0063] Example 7

[0064] Application of the hydrogel substrate material described in Example 1 in the preparation of an electrochemical glucose enzyme sensor.

[0065] (1) curing the hydrogel substrate material described in Example 1 in a mold containing a sensing electrode and an extraction electrode to form a flexible electrochemical glucose enzyme sensor, and attaching the sensor to the skin surface of the inner side of the arm to ensure stable detection;

[0066] (2) The sensor extraction electrode is connected to a constant current source, and the interstitial fluid is extracted through the skin with electric current and stored in the hydrogel. The extraction process lasts for 3 minutes to obtain a certain amount of biological sample;

[0067] (3) Connecting the reaction electrode of the sensor to an electrochemical workstation, using the glucose oxidase inside the hydrogel to catalyze the glucose reaction in the interstitial fluid to generate a detectable current signal to characterize the glucose concentration measured at that time; the entire measurement process lasts for 1 minute;

[0068] (4) Repeat the above steps (2) and (3) to achieve stable and continuous monitoring of blood sugar. The blood sugar prediction value obtained by the electrochemical glucose enzyme sensor is compared with the blood sugar reference value. Figure 4 shown.

[0069] It can be seen from this that the electrochemical glucose enzyme sensor prepared by the hydrogel substrate material can realize stable and continuous monitoring of blood sugar.

[0070] The above-described embodiments are merely descriptions of preferred implementations of the present invention and are not intended to limit the scope of the present invention. Without departing from the design spirit of the present invention, various modifications and improvements made to the technical solutions of the present invention by ordinary engineering and technical personnel in the field shall fall within the protection scope of the claims of the present invention.

Claims

1. A hydrogel substrate material, characterized in that: The invention comprises a hydrogel matrix and a functional filler dispersed in the hydrogel matrix, wherein the hydrogel matrix comprises sulfobetaine, methylenebisacrylamide, ammonium persulfate and tetramethylethylenediamine, and the ratio of sulfobetaine:methylenebisacrylamide:ammonium persulfate:tetramethylethylenediamine is (0.2-0.5) g:(5-20) mg:(5-20) mg:(3-20) μl; the functional filler comprises zinc sulfate, carboxylated cellulose nanofibers, platinum nanoparticles and glucose enzyme, and the mass ratio of the hydrogel matrix to the zinc sulfate, carboxylated cellulose nanofibers, platinum nanoparticles and glucose enzyme is (0.2-0.5) g:(1-12) mg:(20-60) mg:(5-100) mg:(5-100) mg.

2. The hydrogel base material according to claim 1, characterized in that: The glucose enzyme is glucose oxidase, glucose dehydrogenase or catalase.

3. The hydrogel base material according to claim 1, characterized in that: The sulfobetaine:methylenebisacrylamide:ammonium persulfate:tetramethylethylenediamine=0.4g:10mg:10mg:6μl.

4. The hydrogel base material according to claim 1, characterized in that: The mass ratio of the hydrogel matrix to zinc sulfate, carboxylated cellulose nanofibers, platinum nanoparticles, and glucose enzyme is 0.4 g: 8 mg: 30 mg: 10 mg: 50 mg.

5. The method for preparing the hydrogel substrate material according to any one of claims 1 to 4, characterized in that: The specific steps are as follows: (1) mixing sulfobetaine, carboxylated cellulose nanofibers, zinc sulfate, methylenebisacrylamide, ammonium persulfate and PBS buffer, then adding platinum nanoparticles and tetramethylethylenediamine, and stirring to obtain a hydrogel precursor solution; (2) adding the lyophilized glucose enzyme powder to PBS buffer, mixing and stirring to obtain a glucose enzyme solution; (3) The hydrogel precursor solution is mixed with the glucose enzyme solution and then solidified in a water bath to obtain the hydrogel.

6. The method for preparing the hydrogel substrate material according to claim 5, characterized in that: In the step (1), the mass volume ratio of sulfobetaine, carboxylated cellulose nanofibers, zinc sulfate, methylenebisacrylamide, ammonium persulfate, PBS buffer, platinum nanoparticles and tetramethylethylenediamine is (0.2-0.5) g: (20-60) mg: (1-12) mg: (5-20) mg: (5-20) mg: (0.1-1) ml: (5-100) mg: (3-20) μl.

7. The method for preparing the hydrogel substrate material according to claim 5, characterized in that: In the step (3), the volume ratio of the hydrogel precursor solution to the glucose enzyme solution is 1:

1.

8. Use of the hydrogel substrate material according to any one of claims 1 to 4 as a flexible sensor substrate.

9. Use of the hydrogel substrate material according to any one of claims 1 to 4 in preparing diabetes detection equipment.

10. The use according to claim 9, characterized in that: The diabetes detection device is an electrochemical glucose enzyme sensor.

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