Hydrogel bioelectrode patch for electrophysiological signal monitoring and preparation method and application thereof

Abstract

The invention discloses a hydrogel bioelectrode patch for electrophysiological signal monitoring and a preparation method and application of the hydrogel bioelectrode patch for electrophysiological signal monitoring. The preparation method comprises the following steps: adding N-isopropylacrylamide, N-acryloyl phenylalanine and N-(2-ethoxyl) acrylamide into an aqueous solution of 2, 4-ethylenedioxythiophene)-poly (styrene sulfonic acid), and uniformly mixing for the first time to obtain a mixed solution; adding guar gum into the mixed solution, uniformly mixing, adding ammonium persulfate and N, N '-methylene bisacrylamide, and uniformly mixing for the second time; and pouring the uniformly mixed solution into a mold, and carrying out heating cross-linking reaction to obtain the conductive hydrogel. The hydrogel has excellent conductivity, and-OH and-NH2 groups rich in the hydrogel provide reversible adhesion through hydrogen bond establishment and electrostatic interaction with human skin.

Description

Technical Field

[0001] The present invention relates to the technical field of conductive hydrogels, and in particular to a hydrogel bioelectrode patch for electrophysiological signal monitoring, and a preparation method and application thereof. Background Art

[0002] The statements herein merely provide background information related to the present invention and do not necessarily constitute prior art.

[0003] As an intuitive reflection of life activities, electrophysiological signals, including electrocardiogram (ECG) and electromyogram (EMG), carry rich physiological information and have irreplaceable value for health assessment and disease diagnosis.

[0004] Traditional electrophysiological signal acquisition electrodes are mainly divided into two categories: dry electrodes and gel electrodes, each of which has obvious performance bottlenecks. Dry electrodes are usually based on metal or other conductive materials. Although they are easy to deploy immediately, they lack sufficient flexibility and are difficult to form close contact with the skin, resulting in high contact impedance and unstable signal acquisition, which seriously affects the signal quality and feasibility of continuous monitoring. Gel electrodes, represented by Ag / AgCl, improve skin contact, reduce contact impedance, and improve signal acquisition accuracy through gel matrix, but their physical strength and stability are limited. After long-term use, the gel is easy to dry up, and the contact impedance increases accordingly. In addition, the sensitivity of the gel itself to environmental changes greatly reduces the continuity and accuracy of the signal.

[0005] In view of the above technical defects, the development of a new type of electrode must not only have high conductivity to ensure accurate signal acquisition, but also have good biocompatibility so that it can better adapt to the skin surface, reduce displacement and pressure caused by exercise or long-term wearing, and ensure the continuity and stability of signal acquisition. This has become a research hotspot and urgent need in the field of electrophysiological signal monitoring technology. Summary of the invention

[0006] In view of the deficiencies in the prior art, the object of the present invention is to provide a hydrogel bioelectrode patch for electrophysiological signal monitoring and a preparation method and application thereof.

[0007] In order to achieve the above object, the present invention is implemented through the following technical solutions:

[0008] In a first aspect, the present invention provides a method for preparing a hydrogel bioelectrode patch for electrophysiological signal monitoring, comprising the following steps: adding N-isopropylacrylamide, N-acryloylphenylalanine and N-(2-hydroxyethyl)acrylamide to an aqueous solution of poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonic acid), and performing a first mixing to obtain a mixed solution;

[0009] Then, guar gum was added to the mixed solution, and after mixing, ammonium persulfate and N,N′-methylenebisacrylamide were added, and mixed for the second time;

[0010] The mixed solution is poured into a mold and heated for cross-linking reaction to obtain a conductive hydrogel.

[0011] Ammonium persulfate (APS) was used as an initiator and N,N′-methylenebisacrylamide (MBAA) was used as a covalent crosslinking agent.

[0012] The conductive hydrogel electrode patch was prepared by cross-linking guar gum and poly(N-isopropylacrylamide-(N-(2-hydroxyethyl)acrylamide)-(N-acryloyl-phenylalanine)) composites and combining them with poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonic acid).

[0013] The addition of guar gum and poly(N-isopropylacrylamide-(N-(2-hydroxyethyl)acrylamide)-(N-acryloyl-phenylalanine)) enhanced the mechanical properties of the hydrogel through non-covalent interactions with poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonic acid), achieving flexible deformation and energy dissipation. The large number of functional groups in the hydrogel (including hydroxyl, amino, carboxyl and sulfonic acid groups) provide interfacial bonding and can form strong adhesion with the surfaces of various materials. Among them, the abundant -OH and -NH2 groups provide reversible adhesion by establishing hydrogen bonds and electrostatic interactions with human skin.

[0014] Poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonic acid) is a conductive material. When added to the hydrogel matrix, it not only gives the hydrogel excellent conductive properties but also provides a unique volume capacitance, which helps to eliminate the Helmholtz double-layer capacitor effect at the electron-tissue interface, thereby reducing the problem of interface mismatch.

[0015] Poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonate) contains hydrophobic poly(3,4-ethylenedioxythiophene) and hydrophilic poly(styrene sulfonate), which allows it to disperse well in aqueous solution and interact with other polymer networks through electrostatic interactions and hydrogen bonds to build a three-dimensional conductive network. This property gives the hydrogel excellent conductive properties (3.4S / m).

[0016] In some embodiments, the mass ratio of poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonic acid), N-isopropylacrylamide, N-acryloylphenylalanine, N-(2-hydroxyethyl)acrylamide, guar gum, ammonium persulfate and N,N′-methylenebisacrylamide is 1-5:10-15:3-5:3-10:3-7:0.1-0.5:0.01-0.1.

[0017] Preferably, the mass ratio of poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonic acid), N-isopropylacrylamide, N-acryloylphenylalanine, N-(2-hydroxyethyl)acrylamide, guar gum, ammonium persulfate and N,N′-methylenebisacrylamide is 3-5:10-12:3-4:4-6:5-7:0.1-0.3:0.04-0.06, and more preferably 4:11.5:3.75:5:6:0.1:0.05.

[0018] In some embodiments, the temperature at which poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonic acid) is dissolved in water is 20-25°C, preferably 25°C.

[0019] In some embodiments, the temperature of the first mixing is 35-45°C; the temperature of the second mixing is 35-45°C.

[0020] In some embodiments, the temperature of the heating cross-linking reaction is 50-60° C., and the time of the cross-linking reaction is 2-6 hours.

[0021] Preferably, the temperature of the heating cross-linking reaction is 55° C., and the time of the cross-linking reaction is 4 hours.

[0022] In a second aspect, the present invention provides a hydrogel bioelectrode patch for electrophysiological signal monitoring, which is prepared by the preparation method.

[0023] In a third aspect, the present invention provides an application of the hydrogel bioelectrode patch for electrophysiological signal monitoring in the preparation of a wearable flexible sensor.

[0024] The beneficial effects achieved by one or more embodiments of the present invention are as follows:

[0025] (1) The conductive hydrogel provided by the present invention is prepared by cross-linking guar gum and poly(N-isopropylacrylamide-(N-(2-hydroxyethyl)acrylamide)-(N-acryloyl-phenylalanine)) and combining it with poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonic acid). Poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonic acid) contains hydrophobic poly(3,4-ethylenedioxythiophene) and hydrophilic poly(styrene sulfonate), which enables it to be well dispersed in aqueous solution and can interact with other polymer networks through electrostatic interactions and hydrogen bonds to construct a three-dimensional conductive network. This property gives the hydrogel excellent conductive properties (3.4S / m).

[0026] The addition of guar gum and poly(N-isopropylacrylamide-(N-(2-hydroxyethyl)acrylamide)-(N-acryloyl-phenylalanine)) enhanced the mechanical properties of the hydrogel through non-covalent interactions with poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonic acid). The abundant -OH and -NH2 groups in the hydrogel provide reversible adhesion by establishing hydrogen bonds and electrostatic interactions with human skin.

[0027] (2) The present invention adds poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonic acid) to the raw materials to improve the conductivity of the gel electrode, so that the bioelectric signal can be accurately and quickly transmitted to the electrode, realizing real-time signal collection; compared with commercial electrodes, the hydrogel electrode prepared by the present invention has higher signal accuracy and better signal-to-noise ratio.

[0028] The present invention uses poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonic acid), N-isopropylacrylamide, N-(2-hydroxyethyl)acrylamide, and N-acryloylphenylalanine as raw materials. The prepared hydrogel has good stretchability and biocompatibility, can fit the skin tightly, and will not cause skin irritation.

[0029] The addition of guar gum and poly(N-isopropylacrylamide-(N-(2-hydroxyethyl)acrylamide)-(N-acryloyl-phenylalanine)) enhances the mechanical properties of the hydrogel through non-covalent interaction with poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonic acid), increases the strength and toughness of the gel, and leaves no residue when the electrode patch is torn off the skin, nor does it cause skin pain. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] The accompanying drawings in the specification, which constitute a part of the present invention, are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute improper limitations on the present invention.

[0031] Figure 1 is a synthetic flow chart of the conductive hydrogel in an embodiment of the present invention;

[0032] Figure 2 This is a scanning electron microscope image of the conductive hydrogel in Example 1 of the present invention;

[0033] Figure 3 Graphs showing toughness and Young's modulus of conductive hydrogels a, b, c and d obtained after changing the amount of guar gum in Example 2 of the present invention and the hydrogel electrode patch obtained in Example 1;

[0034] Figure 4Graphs showing the toughness and Young's modulus of the conductive hydrogels e, f, g and h obtained by changing the amount of poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonic acid) in Example 3 of the present invention and the hydrogel electrode patch obtained in Example 1;

[0035] Figure 5 This is a diagram showing the adhesion of the conductive hydrogel electrode patch obtained in Example 1 of the present invention to human skin;

[0036] Figure 6 This is a diagram showing the adhesion of the conductive hydrogel electrode patch obtained in Example 1 of the present invention to pig skin;

[0037] Figure 7 This is a graph showing the continuous peel strength of the conductive hydrogel electrode patch obtained in Example 1 of the present invention on pig skin;

[0038] Figure 8 This is a schematic diagram of electrophysiological signals measured after the conductive hydrogel electrode patch obtained in Example 1 of the present invention is connected to a wire;

[0039] Fig. 9 Graphs of human electromyographic signals detected by the conductive hydrogel electrode patch obtained in Example 1 of the present invention and the commercial electrode patch when a grip force that first increases and then decreases is applied;

[0040] Fig.10 This is a comparison diagram of human electromyographic signals detected by the conductive hydrogel electrode patch obtained in Example 1 of the present invention and the commercial electrode patch when a grip force that first increases and then decreases is applied;

[0041] Fig.11 This is a graph of myoelectric signals detected by the hydrogel electrode patch obtained in Example 1 of the present invention and the commercial electrode patch when the human arm performs relaxation-clenching-stretching activities;

[0042] Fig.12 The hydrogel electrode patch obtained in Example 1 of the present invention and the commercial electrode patch detected the electrocardiogram signal of the human body;

[0043] Fig.13 This is a comparison diagram of the amplitudes of the hydrogel electrode patch obtained in Example 1 of the present invention and the commercial electrode patch when detecting the electrocardiogram signal of the human body;

[0044] Fig.14 This is a comparison diagram of the signal-to-noise ratio when the hydrogel electrode patch obtained in Example 1 of the present invention and the commercial electrode patch detect the electrocardiogram signal of the human body;

[0045] Fig.15 The electrocardiogram signals detected by the conductive hydrogel electrode patch obtained in Example 1 of the present invention and the commercial electrode patch before and after human body movement are shown. DETAILED DESCRIPTION

[0046] It should be noted that the following detailed descriptions are illustrative and intended to provide further explanation of the present invention. Unless otherwise specified, all technical and scientific terms used in the present invention have the same meanings as those commonly understood by those skilled in the art to which the present invention belongs.

[0047] In order to enable those skilled in the art to more clearly understand the technical solution of the present invention, the technical solution of the present invention will be described in detail below in conjunction with specific embodiments.

[0048] Example 1

[0049] according to Figure 1 The schematic diagram of the synthesis process for synthesizing the conductive hydrogel is as follows:

[0050] (1) At 25° C., 4 wt % poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonic acid) was added to 8 mL of deionized water and stirred at 700 rpm for 0.2 h; 11.5 wt % N-isopropylacrylamide, 3.75 wt % N-acryloylphenylalanine and 5 wt % N-(2-hydroxyethyl)acrylamide were added to the solution in sequence and stirred at 40° C. and 700 rpm for 0.2 h until the mixture was completely dissolved;

[0051] (2) Add 6 wt % guar gum to the solution of step (1), and stir at 700 rpm at 40° C. for 2 hours until the solution is completely dissolved.

[0052] (3) Add 0.2 wt% ammonium persulfate and 0.05 wt% N,N′-methylenebisacrylamide to the solution of step (2), and stir at 700 rpm for 0.2 hours at a temperature of 40°C until the mixture is completely dissolved. After standing at a high temperature of 55°C for 4 hours, a conductive hydrogel electrode patch is obtained.

[0053] Example 2

[0054] The difference from Example 1 is that the mass fraction of guar gum is changed to 3wt%, 4wt%, 6wt% and 7wt%, respectively, and the obtained conductive hydrogels are a, b, c and d, respectively.

[0055] Example 3

[0056] The difference from Example 1 is that the mass fraction of poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonic acid) is changed to 1wt%, 2wt%, 4wt% and 5wt%, respectively, and the obtained conductive hydrogels are e, f, g and h, respectively.

[0057] The conductive hydrogels obtained in Examples 1 to 4 were characterized respectively.

[0058] Figure 2 is a scanning electron microscope image of the conductive hydrogel obtained in Example 1, as shown Figure 2 As shown, the conductive hydrogel has a three-dimensional network-like porous structure, which can not only provide channels for the migration of ions but also maintain the flexibility and stretchability of the gel.

[0059] Figure 3 Graphs showing the toughness and Young's modulus of the conductive hydrogel electrodes a, b, c and d obtained after changing the amount of guar gum in Example 2 and the conductive hydrogel electrode obtained in Example 1; Figure 4 The graphs are the toughness and Young's modulus of the conductive hydrogel electrodes e, f, g and h obtained by changing the amount of poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonic acid) in Example 3 and the conductive hydrogel electrode obtained in Example 1. It can be seen that the Young's modulus of the hydrogel is close to that of human skin or tissue, indicating that it has good biocompatibility and enhances its stability and comfort in practical applications. Figure 3-4 The results show that the optimal mass ratio of raw materials in conductive hydrogel can be determined.

[0060] Figure 5 and Figure 6 The pictures show that the conductive hydrogel obtained in Example 1 is firmly adhered to the surface of human skin and pig skin. Since the conductive hydrogel has functional groups such as amino and hydroxyl groups, it can form hydrogen bonds and electrostatic interactions with human skin to provide reversible adhesion, and it can firmly adhere to the surface of pig skin and human skin. The hydrogel shows excellent adhesion performance on the skin surface of the experimenter's body, and there is no residue or allergic reaction when peeled off.

[0061] Figure 7 The continuous peel strength diagram of the conductive hydrogel electrode patch obtained in Example 1 on pig skin. Even after 5 repeated peeling / adhesion cycles, the hydrogel still maintains good adhesion. The excellent adhesion performance of the hydrogel can reduce the displacement and pressure caused by exercise or long-term wearing, and ensure the continuity and stability of signal acquisition in practical applications.

[0062] Figure 8The schematic diagram of collecting human electrophysiological signals after the conductive hydrogel electrode patch obtained in Example 1 is connected to a wire. The electrode patch is designed to be directly adhered to the surface of human skin, such as the arm or chest, and is connected to a data acquisition device through a wire to achieve real-time monitoring and recording of human electrophysiological signals. Through experiments, the hydrogel electrode patch prepared in Example 1 was functionally tested to evaluate its performance in detecting human electromyographic signals. During the test, the electrode patch was fixed on the subject's arm, and then a series of experiments with controlled variables were conducted to simulate the subject applying different grip strengths.

[0063] The experimental results show that when the subjects apply the same weight of grip force, the electrode patch can stably record the corresponding electromyographic signals. Fig. 9 The intensity change of the electromyographic signal under different grip force conditions is further demonstrated. It can be observed that the amplitude of the electromyographic signal increases with the increase of grip force and decreases with the decrease of grip force, which verifies that the conductive hydrogel electrode patch of the present invention has high sensitivity and stability in electrophysiological signal detection, and also confirms its potential in practical applications, especially in scenarios where accurate monitoring of human muscle activity is required.

[0064] Fig.10 As shown, a comparative analysis of the amplitude of myoelectric signals between the conductive hydrogel electrode of the present invention and the traditional commercial electrode patch (model: X-1 disposable ECG electrode, silver / silver chloride·Ag / AgCl, purchased from Hangzhou Xunda Radio Equipment Co., Ltd.) is shown. Through quantitative calculation, it is found that the amplitude value of the conductive hydrogel electrode of the present invention is significantly higher than that of the traditional electrode. This result intuitively reflects the superiority of the conductive hydrogel electrode in signal acquisition. This enhanced signal strength not only means higher signal transmission efficiency, but also indicates that the user will have a more comfortable experience when wearing it.

[0065] Fig.11 The electromyographic signals of human arm movements were monitored using the conductive hydrogel electrode patch of the present invention and the traditional commercial electrode patch (model: X-1 disposable ECG electrode, silver / silver chloride·Ag / AgCl, purchased from Hangzhou Xunda Radio Equipment Co., Ltd.). Through in-depth analysis of these signals, researchers and medical professionals can understand the details of muscle activity, including key information such as muscle activity patterns, synergy, and force output. These data have important reference value in the fields of motion analysis, training optimization, and rehabilitation assessment.

[0066] Fig.12The conductive hydrogel electrode patch obtained in Example 1 and the commercial electrode patch (model: X-1 disposable ECG electrode, silver / silver chloride·Ag / AgCl, merchant: Hangzhou Xunda Radio Equipment Co., Ltd.) detected human ECG signals. This shows the application potential of the conductive hydrogel electrode patch in multimodal physiological signal monitoring.

[0067] Fig.13 and 14 The results show that when detecting ECG signals, a detailed comparative analysis of the amplitude and signal-to-noise ratio of ECG signals was performed. The results show that the conductive hydrogel electrode patch obtained in Example 1 is superior to the traditional commercial electrode patch in both amplitude and signal-to-noise ratio. These data strongly support the application prospects of conductive hydrogel electrode patches in the field of medical monitoring in the future, and are likely to gradually replace existing commercial electrode patches and become the mainstream choice in the market.

[0068] Fig.15 As shown, the ability of the conductive hydrogel electrode patch obtained in Example 1 to monitor ECG signals before and after human exercise is demonstrated. Considering the significant effect of exercise on cardiac function, the electrode patch of the present invention has important practical significance in evaluating exercise effects, monitoring heart rate changes, and preventing exercise risks. Appropriate exercise can strengthen heart muscles and improve heart work efficiency, and the electrode patch of the present invention can provide accurate physiological data support to achieve this goal.

[0069] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A method for preparing a hydrogel bioelectrode patch for electrophysiological signal monitoring, characterized in that: The method comprises the following steps: adding N-isopropylacrylamide, N-acryloylphenylalanine and N-(2-hydroxyethyl)acrylamide to an aqueous solution of poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonic acid), and performing a first mixing to obtain a mixed solution; Then, guar gum was added to the mixed solution, and after mixing, ammonium persulfate and N,N′-methylenebisacrylamide were added, and mixed for the second time; The mixed solution is poured into a mold and heated for cross-linking reaction to obtain a conductive hydrogel.

2. The method for preparing a hydrogel bioelectrode patch for electrophysiological signal monitoring according to claim 1, characterized in that: The mass ratio of poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonic acid), N-isopropylacrylamide, N-acryloylphenylalanine, N-(2-hydroxyethyl)acrylamide, guar gum, ammonium persulfate and N,N′-methylenebisacrylamide is 1-5:10-15:3-5:3-10:3-7:0.1-0.5:0.01-0.

1.

3. The method for preparing a hydrogel bioelectrode patch for electrophysiological signal monitoring according to claim 2, characterized in that: The mass ratio of poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonic acid), N-isopropylacrylamide, N-acryloylphenylalanine, N-(2-hydroxyethyl)acrylamide, guar gum, ammonium persulfate and N,N′-methylenebisacrylamide is 3-5:10-12:3-4:4-6:5-7:0.1-0.3:0.04-0.

06.

4. The method for preparing a hydrogel bioelectrode patch for electrophysiological signal monitoring according to claim 2, characterized in that: The mass ratio of poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonic acid), N-isopropylacrylamide, N-acryloylphenylalanine, N-(2-hydroxyethyl)acrylamide, guar gum, ammonium persulfate and N,N′-methylenebisacrylamide is 4:11.5:3.75:5:6:0.1:0.

05.

5. The method for preparing a hydrogel bioelectrode patch for electrophysiological signal monitoring according to claim 1, characterized in that: The temperature at which poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonic acid) is dissolved in water is 20-25°C.

6. The method for preparing a conductive hydrogel electrode patch according to claim 5, characterized in that: The temperature at which poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonic acid) is dissolved in water is 25°C.

7. The method for preparing a hydrogel bioelectrode patch for electrophysiological signal monitoring according to claim 1, characterized in that: The temperature of the first mixing is 35-45°C; the temperature of the second mixing is 35-45°C.

8. The method for preparing a hydrogel bioelectrode patch for electrophysiological signal monitoring according to claim 1, characterized in that: The temperature of the heating cross-linking reaction is 50-60°C, and the time of the cross-linking reaction is 2-6h.

9. A hydrogel bioelectrode patch for electrophysiological signal monitoring, characterized in that: Prepared by the preparation method described in any one of claims 1 to 8.

10. Use of the hydrogel bioelectrode patch for electrophysiological signal monitoring according to claim 9 in the preparation of a wearable flexible sensor.

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