Preparation method and application of in-situ curable conductive biogel

Abstract

The present invention discloses a method for preparing an in-situ curable conductive biogel and its application. The biogel precursor solution includes a biomolecule aqueous solution and a natural moisturizing factor component, and is a temperature-sensitive biogel. The liquid phase biogel precursor solution can undergo rapid crosslinking and curing when the temperature drops to a certain range. First, a uniformly mixed biogel precursor solution is obtained, which can undergo a solution-gel phase transition under mild conditions, thereby directly curing and forming in situ on uneven biological tissue surfaces, such as plant tissues such as leaves, stems, etc., and skin. The application of the product of the present invention in flexible wearable electronic devices can achieve highly sensitive acquisition of biological epidermal electrophysiological signals and bioelectrical impedance. The preparation method of the conductive biogel that can be cured in situ is simple, easy, low-cost, and suitable for large-scale production and promotion and application.

Description

Technical Field

[0001] The present invention relates to a preparation method and application of a conductive biological medium in the field of biomaterial technology, and more particularly to a preparation method and application of a conductive biogel capable of in-situ curing. Background Art

[0002] Traditional epidermal bioelectronic devices suffer from large size, rigid materials, and insufficient flexibility, making it difficult to form close and effective contact with soft biological structures with complex surface microstructures. This mechanical property mismatch severely impairs the efficiency and quality of signal acquisition and transmission at the electrode-biological interface. Therefore, there is a need to provide a material that can form an effective information exchange interface between traditional electrodes and soft biological tissues, thereby addressing the signal interface adhesion and signal transmission issues between the electrode and biological interface.

[0003] In recent years, with the continuous development of materials science, the emergence of hydrogels has provided new possibilities for the adhesion between electrodes and biological interfaces. Hydrogels are a type of "soft" material with a three-dimensional network structure and rich water content, which has good flexibility and adhesion.

[0004] However, the surface texture of biological tissues poses challenges for the effective adhesion of hydrogels to their surfaces. For example, the uneven and irregular surfaces of biological tissues create obstacles to close contact with electrodes, making it difficult for conventional hydrogels to adapt and adhere to them.

[0005] Secondly, hydrogels have a high water content and are prone to losing water and their inherent properties in complex environments.

[0006] Therefore, developing a biocompatible gel material that can effectively and stably adhere to the irregular surface of biological tissue is a key and difficult issue. Summary of the Invention

[0007] In order to solve the problems existing in the background technology, the purpose of the present invention is to overcome the above-mentioned defects and shortcomings existing in the prior art and provide a conductive biogel that can be cured in situ.

[0008] Another object of the present invention is to provide a method for preparing the in-situ curable conductive biogel.

[0009] Another object of the present invention is to provide applications of the in-situ curable conductive biogel.

[0010] The above-mentioned object of the present invention is achieved through the following technical solutions:

[0011] 1. An in-situ curable conductive biogel:

[0012] The biogel solution is solidified in situ, and the biogel solution comprises the following components:

[0013] The invention relates to a gelatin solution having temperature phase transition characteristics and polypyrrolidone carboxylic acid sodium (PCA-Na) having good water retention and ion conductivity and capable of being stably dispersed in an aqueous phase system.

[0014] The mass ratio of the gelatin solution to sodium polypyrrolidone carboxylate is 2:5 to 1:2.

[0015] Preferably, the final concentration of gelatin in the biogel solution is 15-25 wt % to ensure the formation of a three-dimensional network base structure of the hydrogel.

[0016] Preferably, the final concentration of sodium polypyrrolidone carboxylate in the biogel solution is 20-40 wt %.

[0017] The gelatin in the biogel solution provides a three-dimensional hydrogel network structure, and the gelatin undergoes phase transitions of gelation and dissolution at different temperatures.

[0018] At low temperatures, gelatin molecules form a stable double-helix structure with strong hydrogen bonding, resulting in cross-linking between gelatin molecules. This cross-linking structure is the basis for gelatin formation. When the temperature reaches the melting point of gelatin, the gelatin's gel structure is destroyed, the intermolecular cross-links are unwound, and the gelatin gradually transforms into a sol state. PCA-Na is evenly dispersed in the gelatin solution, enhancing the biogel's mechanical properties and water retention. It also introduces excellent and adjustable ionic conductivity. The thermal transition properties of the biogel solution give it in-situ curing properties, allowing the in-situ cured biogel electrode to stably adhere to uneven biological tissue surfaces while avoiding interference caused by tissue deformation.

[0019] 2. Preparation method of conductive biogel:

[0020] The two components of gelatin and sodium polypyrrolidone carboxylate are dispersed in aqueous solution in sequence, mixed evenly to obtain a biogel solution with uniform performance, and the biogel solution is solidified in situ to obtain a conductive biogel.

[0021] The conductive biogel product of the present invention can be used in applications of conductive media and electrical signal measurement, and can be used as a binder and conductive medium / electrical signal measurement at the same time.

[0022] 3. Application methods of conductive biogel:

[0023] Tape molds of different numbers, sizes and shapes are pasted on the surface of biological tissue in advance, and the biogel solution is directly dropped on the surface of the biological tissue, and solidified in situ on the surface of the biological tissue after cooling.

[0024] The present invention can select the proportion of biogel solutions with different components according to needs. The precursor aqueous solution (liquid biogel solution) can undergo solution-gel phase transition under temperature changes and solidify into a composite hydrogel with a three-dimensional network structure.

[0025] The biological tissue surface is a skin surface with a three-dimensional microstructure or an uneven biological tissue surface.

[0026] Preferably, the application site of the in situ cured conductive biogel includes but is not limited to the skin with a complex three-dimensional microstructure, and other uneven biological tissue surfaces.

[0027] The in-situ curable conductive biogel of the present invention can serve as both an adhesive and a conductive medium, directly constructing an effective contact interface with rigid electrodes or bioelectronic devices on irregular biological surfaces, and achieving high-quality monitoring of epidermal bioelectric signals (epidermal electromyographic signals, electrocardiographic signals, electroencephalographic signals, etc.).

[0028] The in-situ curing described in the present invention is to drop a liquid biogel solution (liquid above a certain temperature) onto the target substrate surface. As the solution temperature decreases, it solidifies to form a gel on the substrate surface, which is called in-situ curing.

[0029] Normal curing is to process it into gel in the mold and then stick it on the target substrate surface.

[0030] The in-situ solidified biogel of the present invention is a temperature-sensitive biogel, and the liquid phase biogel precursor solution can undergo rapid cross-linking and solidification when the temperature drops to a certain range.

[0031] The biogel precursor solution includes a biomolecule aqueous solution and a natural moisturizing factor component. The present invention first obtains a uniformly mixed biogel precursor solution, which can undergo a solution-gel phase transition under mild conditions, thereby directly solidifying and forming in situ on uneven biological tissue surfaces, such as plant tissues such as leaves, stems, etc., as well as skin.

[0032] The application of the in-situ curing biogel electrode of the present invention in flexible wearable electronic devices can achieve highly sensitive acquisition of biological epidermal electrophysiological signals and bioelectrical impedance; the preparation method of the conductive biogel that can be cured in situ is simple, easy, low-cost, and suitable for large-scale production and promotion and application.

[0033] The beneficial effects of the present invention are:

[0034] (1) The present invention adopts in-situ curing technology and, under relatively mild reaction conditions that do not damage biological tissues, utilizes the unique properties of bio-hydrogels to adhere rigid electrodes or bio-electronic devices to irregular biological tissue surfaces. The bio-gel preparation process of the present invention does not require complex technical means, is simple to operate, has low cost, and can be produced and promoted on a large scale. At the same time, the shape and size of the bio-hydrogel are easy to adjust, making it convenient to connect with other epidermal bio-electronic devices and having a wide range of application scenarios.

[0035] (2) The in-situ curable conductive biogel of the present invention is made of biocompatible natural materials and does not cause unnecessary damage to biological tissues. Furthermore, PCA-Na has excellent moisture retention properties, effectively solving the problem of traditional hydrogels losing their function due to water loss, and has broad practical application value. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] Figure 1 These are plant-electrode contact impedance spectra collected for the conductive biogels based on in-situ curing (A) and conventional curing (B) according to Example 1 of the present invention.

[0037] Figure 2 This is a graph of myoelectric signals collected based on the in-situ cured conductive biogel according to Example 2 of the present invention.

[0038] Figure 3 This is a graph of electrocardiographic signals collected based on the in-situ cured conductive biogel according to Example 3 of the present invention.

[0039] Figure 4 This is a graph of EEG signals collected based on the in-situ cured conductive biogel according to Example 4 of the present invention. DETAILED DESCRIPTION

[0040] The present invention will be further described below with reference to the accompanying drawings and specific implementations.

[0041] The embodiments of the present invention are as follows:

[0042] Example 1:

[0043] This embodiment provides a conductive bio-hydrogel for measuring plant-electrode contact impedance. Using a two-electrode test system to measure the contact impedance between the epidermis of a tomato plant and an electrode, the conductive hydrogel is used to effectively bond a tomato plant leaf to an Ag / AgCl electrode sheet. The two test electrodes are affixed to either side of the leaf vein of the tomato plant.

[0044] In this embodiment, the specific steps are as follows:

[0045] (1) 0.4 g of gelatin was added to 1.04 mL of deionized water, soaked for 1 h, and then stirred at 50 °C for 2 h to form a uniform gelatin solution; 0.96 g of sodium pyrrolidonecarboxylate (PCA-Na) was added to the uniform gelatin solution, and then stirred at 50 °C for 2 h to form a biogel precursor solution.

[0046] (2) Two pieces of tape molds are pasted on both sides of the veins of the tomato plant leaves. The blank area of ​​the tape mold is designed to be 1cm×1cm, and the distance between the tape edges is 5mm. Then, the liquid biogel precursor solution is poured into the tape mold, and the Ag / AgCl electrode sheet is covered on the surface before it cools down. After it cools down to room temperature, the biogel precursor solution solidifies in situ on the leaf surface and forms good adhesion with the Ag / AgCl electrode sheet. Then, the Ag / AgCl electrode sheet is led out with a wire. For the measurement of ordinary curing, the biogel precursor solution is first cured and then attached to the plant surface. The other steps are the same.

[0047] (3) Connect the electrode lead wires of the epidermal hydrogel patch to the electrochemical workstation and select the AC impedance measurement mode. One electrode is connected to the working electrode clamp, and the other electrode is connected to the reference electrode and the counter electrode clamp. After the measurement starts, the electrical impedance spectrum of the contact impedance value changing with frequency (0.1Hz~100000Hz) can be obtained in real time. The bioelectrical impedance spectrum collected based on the in situ solidified conductive biogel is compared with the bioelectrical impedance spectrum collected based on the ordinary solidified hydrogel. The results are as follows: Figure 1 As shown in (A) and (B), the bioimpedance value collected by the in situ curing method is much lower than that of the conventional curing method, indicating that the in situ curing properties of biohydrogels have significant advantages in reducing the impedance of the electrode-tissue interface.

[0048] Example 2:

[0049] This embodiment provides a conductive bio-hydrogel for measuring electromyographic signals. For example, to collect electromyographic signals from the biceps brachii, two recording electrodes and one reference electrode are required. The electrodes are commercially available Ag / AgCl electrodes, which adhere to the skin epidermis using the conductive bio-hydrogel.

[0050] In this embodiment, the specific steps are as follows:

[0051] (1) 0.45 g of gelatin was added to 1.04 mL of deionized water, soaked for 1 h, and then stirred at 50 °C for 2 h to form a uniform gelatin solution; 0.96 g of sodium pyrrolidonecarboxylate (PCA-Na) was added to the uniform gelatin solution, and then stirred at 50 °C for 2 h to form a biogel precursor solution.

[0052] (2) Two tape molds with a 2cm distance between them were pasted on the belly of the biceps brachii muscle, and one tape mold was pasted on the root of the muscle. The empty space of the tape mold was designed to be 1cm×1cm. Then, the liquid biogel precursor solution was poured into the tape mold. Before it cooled, the Ag / AgCl electrode sheet was covered on the surface. After it cooled to room temperature, the biogel precursor solution solidified in situ on the skin surface and formed good adhesion with the Ag / AgCl electrode sheet. Then, the Ag / AgCl electrode sheet was led out with a wire.

[0053] (3) Connect the electrode lead wire to the multi-channel physiological recorder, set the original channel path and acquisition parameters, and then record the real-time electromyographic signal. Figure 2 As shown in the figure, it can be seen that the conductive bio-hydrogel can enable the test electrode to form effective contact with the skin surface, thereby achieving high-quality acquisition of electromyographic signals.

[0054] Example 3:

[0055] This embodiment provides a conductive bio-hydrogel for measuring ECG signals. A three-electrode test system is used, with electrodes attached to the upper right, upper left, and lower left sides of the chest and abdomen. The electrodes are commercially available Ag / AgCl electrodes, which adhere to the skin epidermis using the conductive bio-gel.

[0056] In this embodiment, the specific steps are as follows:

[0057] (1) 0.45 g of gelatin was added to 1.04 mL of deionized water, soaked for 1 h, and then stirred at 50 °C for 2 h to form a uniform gelatin solution; 0.96 g of sodium pyrrolidonecarboxylate (PCA-Na) was added to the uniform gelatin solution, and then stirred at 50 °C for 2 h to form a biogel precursor solution.

[0058] (2) Three pieces of tape molds were pasted on the upper right, upper left, and lower left parts of the chest and abdomen. The blank areas of the tape molds were designed to be 1 cm × 1 cm. Then, the liquid biogel precursor solution was poured into the tape molds. Before it cooled, the Ag / AgCl electrode sheet was covered on the surface. After it cooled to room temperature, the biogel precursor solution solidified in situ on the skin surface and formed good adhesion with the Ag / AgCl electrode sheet. The Ag / AgCl electrode sheet was then led out with a wire.

[0059] (3) Connect the electrode lead wire to the multi-channel physiological recorder, set the original channel path and acquisition parameters, and then record the real-time ECG signal. Figure 3 As shown in the figure, it can be seen that the conductive bio-hydrogel can enable the test electrode to form effective contact with the skin surface, thereby achieving high-quality acquisition of ECG signals.

[0060] Example 4:

[0061] This embodiment provides a conductive bio-hydrogel for EEG signal measurement. A three-electrode test system is used: a reference electrode is attached behind the left ear, a ground electrode is attached behind the right ear, and a working electrode is attached to the occipital region of the scalp. The electrodes are the same as those provided with the EEG signal acquisition instrument, and the conductive bio-gel adheres to the skin or scalp surface.

[0062] In this embodiment, the specific steps are as follows:

[0063] (1) 0.5 g of gelatin was added to 1.04 mL of deionized water, soaked for 1 h, and then stirred at 50 °C for 2 h to form a uniform gelatin solution; 0.96 g of sodium pyrrolidone carboxylate (PCA-Na) was added to the uniform gelatin solution, and then stirred at 50 °C for 2 h to form a biogel precursor solution.

[0064] (2) The liquid biogel was then dripped onto the back of the left ear, the back of the right ear, and the occipital area of ​​the scalp. The electrodes for signal acquisition were covered on the surface before it cooled down. After it cooled down to room temperature, the biogel precursor solution solidified in situ on the surface of the skin and scalp while also forming good adhesion with the electrodes, thus establishing a good signal transmission interface between the skin and scalp and the test electrodes.

[0065] (3) Connect the electrode lead wire to the EEG signal recorder, set the original channel path and acquisition parameters, and then record the real-time EEG signal. Figure 4 As shown in the figure, it can be seen that the conductive bio-hydrogel can enable the test electrode to form effective contact with the skin and scalp surface, thereby achieving high-quality acquisition of EEG signals.

[0066] It should be noted that the above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art will be able to modify the technical solutions described in the aforementioned embodiments or replace parts thereof with equivalents. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention shall be included within the scope of protection of the present invention.

Claims

1. An application of a conductive biogel, characterized by: The conductive biogel is solidified by a biogel solution, and the biogel solution comprises the following components: a gelatin solution and sodium pyrrolidone carboxylate; Alternatively, the conductive biogel is obtained by dispersing gelatin and sodium pyrrolidonecarboxylate in an aqueous solution, mixing the two components to obtain a biogel solution with uniform properties, and then solidifying the biogel solution in situ; Application of the conductive biogel in conductive media and electrical signal measurement; It is used as both a binder and a conductive medium.

2. The use of a conductive biogel according to claim 1, characterized in that: The mass ratio of the gelatin to sodium pyrrolidonecarboxylate is 2:5 to 1:

2.

3. The use of a conductive biogel according to claim 1, characterized in that: The final concentration of gelatin in the biogel solution is 15-25 wt %.

4. The use of a conductive biogel according to claim 1, characterized in that: The final concentration of sodium pyrrolidonecarboxylate in the biogel solution is 20-40 wt %.

5. A method for applying a conductive biogel, characterized in that: The conductive biogel is solidified by a biogel solution, and the biogel solution comprises the following components: a gelatin solution and sodium pyrrolidone carboxylate; Alternatively, the conductive biogel is obtained by dispersing gelatin and sodium pyrrolidonecarboxylate in an aqueous solution, mixing the two components to obtain a biogel solution with uniform properties, and then solidifying the biogel solution in situ; The conductive biogel is pre-pasted with tape molds of different numbers, sizes and shapes on the surface of biological tissues, and the biogel solution is directly dropped on the surface of the biological tissues and solidified in situ on the surface of the biological tissues after cooling.

6. The application method according to claim 5, characterized in that: The biological tissue surface is a skin surface with a three-dimensional microstructure or an uneven biological tissue surface.

7. The method for applying the conductive biogel according to claim 5, wherein: The mass ratio of the gelatin to sodium pyrrolidonecarboxylate is 2:5 to 1:

2.

8. The method for applying the conductive biogel according to claim 5, wherein: The final concentration of gelatin in the biogel solution is 15-25 wt %.

9. The method for applying the conductive biogel according to claim 5, wherein: The final concentration of sodium pyrrolidonecarboxylate in the biogel solution is 20-40 wt %.

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