Chemically detachable hydrogel electrodes for physiological electrical measurements, methods of using the same

Abstract

The application provides a chemical detachable hydrogel electrode for physiological electrical measurement, a use method thereof, and the electrode comprises a flexible base layer, a flexible packaging layer, a flexible electrode array layer integrated with internal circuits and one or more electrode points, a hydrogel base layer, a detachable hydrogel interface layer, and separately stored polymer solution, metal ion anchoring solution and metal chelating agent solution; the flexible electrode array layer is arranged in a flexible frame body formed by the flexible base layer and the flexible packaging layer, the electrode points extend out of the flexible frame body, the hydrogel base layer covers the electrode points, the detachable hydrogel interface layer is detachably arranged on the hydrogel base layer, and the combination and detachment with the hydrogel base layer are realized through the polymer solution, the metal ion anchoring solution and the metal chelating agent solution. The electrode can realize the detachable hydrogel interface through chemical solution immersion, realize the repeated use of the electrode, and reduce the cross-infection risk.

Description

Technical Field

[0001] This invention relates to the field of biomedical device technology, specifically to a chemically detachable hydrogel electrode for physiological electrophysiological measurement and its method of use. Background Technology

[0002] Electrodes used for human physiological electrical measurements have important applications in disease treatment and health monitoring. Among them, flexible electrodes, with their good flexibility, can better adapt to the surface of complex biological tissues. When in contact with human tissues, they can significantly reduce the risk of physical damage to human tissues compared to traditional electrodes, thus ensuring the stable acquisition of physiological electrical signals.

[0003] However, existing flexible electrodes for physiological electrical measurements still have many shortcomings. In terms of materials, the modulus of the electrode is mismatched with that of the tissue (such as brain tissue during craniotomy), making it prone to damage to the brain tissue due to stress generated during long-term monitoring. Furthermore, electrodes used in surgical situations or on the surface of open wounds are mostly single-use products. This is primarily because reusing existing flexible electrodes in surgical environments or under open wound conditions would pose a significant risk of cross-infection, endangering the patient's health and safety. However, single-use flexible electrodes result in high application costs, increasing the medical burden on patients.

[0004] Therefore, a flexible electrode that is highly compatible with human tissues (such as brain tissue) is needed, which can adhere closely to the tissue surface to ensure high accuracy and stability of physiological electrical measurements, realize real-time monitoring and feedback during surgery or at wound sites, and at the same time, can be reused through specific methods to reduce costs and reduce the risk of cross-infection. Summary of the Invention

[0005] To address the problems existing in the background art, the present invention provides a chemically removable hydrogel electrode for physiological electrophysiological measurement and its usage method. The electrode can measure the electrical signals of tissues. The removable hydrogel interface is bonded to and detached from the hydrogel base layer by immersion in a chemical solution, thereby enabling the electrode to be reused, reducing costs and the risk of cross-infection.

[0006] The technical solution of the present invention to solve the above-mentioned technical problems is as follows:

[0007] In a first aspect, the present invention provides a chemically detachable hydrogel electrode for physiological electrometry, comprising a flexible substrate layer, a flexible encapsulation layer, a flexible electrode array layer integrating internal circuitry and one or more electrode points, a hydrogel substrate layer, a detachable hydrogel interface layer, and separately stored polymer solutions, metal ion anchoring solutions, and metal chelating agent solutions; the flexible substrate layer and the flexible encapsulation layer together form a flexible frame body, the flexible electrode array layer is disposed within the flexible frame body, one or more electrode points extend out of the flexible frame body through windows on the flexible encapsulation layer, the hydrogel substrate layer is disposed on the flexible encapsulation layer and covers the electrode points, and the detachable hydrogel interface layer is detachably disposed on the hydrogel substrate layer, for use with... It adheres to human tissue; the solute in the polymer solution is a water-soluble polymer containing carboxyl groups, and the metal anchoring solution is a metal cation / citric acid aqueous solution, where the metal cation is divalent or trivalent; the removable hydrogel interface layer achieves bonding and disassembly with the hydrogel substrate layer through the polymer solution, the metal ion anchoring solution, and the metal chelating agent solution; during use, the polymer solution and the metal ion anchoring solution form an anchoring network of metal cations and polymers on the hydrogel substrate layer and the removable hydrogel interface layer, respectively, and anchor the two by external pressure; after use, the anchoring network of metal cations and polymers is destroyed by soaking in the metal chelating agent solution, thereby achieving the disassembly of the removable hydrogel interface layer.

[0008] The principle of this invention is as follows: During use, the metal cations in the hydrogel base layer and the detachable hydrogel interface layer form metal chelate bonds with the carboxyl groups in the polymer, thus binding the two hydrogel layers together. After use, the hydrogel is soaked in a metal chelating agent solution. As the metal chelating agent solution gradually penetrates into the interface layer of the two gel layers, the chelation between the metal cations and the ionic groups in the metal chelating agent solution is stronger, and the chelation between the metal cations and the polymer is destroyed, thereby breaking the bond between the two hydrogel layers and allowing the detachable hydrogel interface layer to be removed from the electrode.

[0009] The beneficial effects of this invention are as follows: This invention achieves the bonding and disassembly of the removable hydrogel interface layer and the hydrogel base layer through simple chemical solution immersion. The electrode can be reused by only replacing the removable hydrogel interface layer, which reduces costs and the risk of cross-infection.

[0010] According to the above scheme, the polymer solution is an aqueous solution of a polymer with a mass fraction of 5wt%-10wt%.

[0011] The metal ion anchoring solution comprises a metal cation salt, citric acid, and water, with the pH adjusted to 2.7-3.3 using sodium hydroxide. The mass fractions of the metal cation salt and citric acid range from 1 wt% to 4 wt% and 1 wt% to 5 wt%, respectively.

[0012] The metal chelating agent solution comprises a metal chelating agent, acetic acid, and water, with the mass fractions of the metal chelating agent and acetic acid being 5wt%-15wt% and 0.5wt%-2wt%, respectively.

[0013] According to the above scheme, the polymer is one or more selected from polyacrylic acid, hyaluronic acid, sodium alginate, polyaspartic acid, and carboxymethyl cellulose; the metal cation is Fe. 3+ Zr 4+ And Al 3+ One or more of the following; the metal chelating agent is EDTANa4.

[0014] In some specific embodiments of the present invention, the polymer is polyacrylic acid, and the high-impact metal cation is Fe. 3+ The molecular weight of polyacrylic acid is 100,000-240,000.

[0015] According to the above scheme, the hydrogel base layer and the removable hydrogel interface layer contain methacryloyloxyethyltrimethylammonium chloride (MATAC) microspheres.

[0016] Methacryloxyethyltrimethylammonium chloride (MATAC) microspheres can improve the anti-swelling and mechanical properties of the hydrogel substrate and the removable hydrogel interface layer, thereby reducing their swelling rate during immersion in solution.

[0017] According to the above scheme, the hydrogel base layer and the removable hydrogel interface layer contain conductive materials.

[0018] According to the above scheme, the conductive materials in the hydrogel base layer and the removable hydrogel interface layer can be independently selected from any one of LiCl, CaCl2, NaCl, PEDOT:PSS, polyaniline and polypyrrole.

[0019] Adding conductive materials can give the two layers of hydrogel good conductivity.

[0020] According to the above scheme, the removable hydrogel interface layer contains dopamine-modified sodium alginate (Alg-DA), acrylic acid (AAC), and N-acryloyloxysuccinimide (AAC-NHS). Alg-DA can give the removable hydrogel interface layer good adhesion, while AAC and AAC-NHS can increase its wet tack, so that the removable hydrogel interface layer can be stably adhered to the tissue surface.

[0021] According to the above scheme, the internal circuit is branched, and multiple electrode points are located at the ends of the branches of the internal circuit. The hydrogel substrate is divided into multiple non-connected regions that correspond one-to-one with the electrode points and cover the corresponding electrode points respectively. The detachable hydrogel interface layer includes multiple non-connected regions that correspond one-to-one with the multiple regions of the hydrogel substrate and are bonded to them.

[0022] Secondly, the present invention provides a method for using the above-mentioned chemically detachable hydrogel electrode for physiological electrometry, comprising the following steps:

[0023] 1) Before use, the polymer solution is added to the side of the hydrogel base layer and the removable hydrogel interface layer that need to be bonded, so that the polymer diffuses to form a polymer network. Then, metal ion anchoring solution is added to form an anchoring network between metal cations and polymer. Then, the two hydrogel layers that need to be bonded are placed face to face and squeezed for a certain period of time to bond the hydrogel base layer and the removable hydrogel interface layer together.

[0024] 2) The removable hydrogel interface layer is adhered to human tissue for physiological electrical measurements;

[0025] 3) After use, soak the removable hydrogel interface layer with a metal chelating agent solution, ensuring that the metal chelating agent solution does not exceed the bonding surface between the two hydrogel layers. After soaking for a certain period of time, the hydrogel base layer and the removable hydrogel interface layer can be separated.

[0026] 4) Soak the hydrogel substrate in deionized water for a certain period of time to remove residual metal chelating agents;

[0027] 5) When using it again, replace the hydrogel interface layer and repeat steps 1)-4 above.

[0028] Thirdly, the present invention provides a method for preparing the above-mentioned chemically detachable hydrogel electrode for physiological electrometry, comprising the following steps:

[0029] S1. Prepare methacryloyloxyethyltrimethylammonium chloride microspheres, dopamine-modified sodium alginate, benzophenone solution, polymer solution, metal ion anchoring solution and metal chelating agent solution respectively.

[0030] S2. Precursor solutions for the hydrogel base layer and the removable hydrogel interface layer were prepared separately: Acrylamide, LiCl, D-sorbitol, and sodium alginate were dissolved in deionized water, and then a photoinitiator and crosslinking agent were added. Methacryloxyethyltrimethylammonium chloride microspheres were then added, and the mixture was mechanically stirred for a certain period of time to prepare the hydrogel base layer precursor solution; Acrylamide, dopamine-modified sodium alginate, PEDOT:PSS, acrylic acid, and N-acryloyloxysuccinimide were dissolved in deionized water, and then a photoinitiator and crosslinking agent were added. Finally, methacryloxyethyltrimethylammonium chloride microspheres were added, and the mixture was mechanically stirred for a certain period of time to prepare the removable hydrogel interface layer precursor solution.

[0031] S3. Fabricate and form a flexible substrate layer, a flexible electrode array layer, and a flexible encapsulation layer;

[0032] S4. Soak the area around the electrode point at the end of each branch of the flexible electrode array layer in benzophenone solution for a certain period of time.

[0033] S5. The hydrogel substrate precursor solution is poured into the electrode points at the end of each branch of the flexible electrode array layer through a mold. After being irradiated with ultraviolet light, the hydrogel substrate layer polymerizes at the electrode points. The detachable hydrogel interface layer precursor solution is poured into a mold of the same shape. After being irradiated with ultraviolet light, the hydrogel of the detachable hydrogel interface layer polymerizes.

[0034] According to the above scheme, the photoinitiator is α-ketoglutaric acid, and the crosslinking agent is N,N'-methylenebisacrylamide.

[0035] The preparation method is simple, efficient, and has low manufacturing cost. Attached Figure Description

[0036] Figure 1 This is an overall exploded view of the chemically detachable hydrogel electrode for physiological electrometry according to Embodiment 1 of the present invention.

[0037] Figure 2 This is a top view of the overall schematic diagram of the chemically detachable hydrogel electrode for physiological electrometry according to Embodiment 1 of the present invention.

[0038] Figure 3 This invention relates to a method for preparing and using a chemically detachable hydrogel electrode for physiological electrometry.

[0039] Figure 4 This describes the disassembly process of the chemically detachable hydrogel electrode for physiological electrometry in Embodiment 2 of the present invention.

[0040] In the figure, 1 is the flexible substrate layer, 2 is the flexible electrode array layer, 3 is the flexible encapsulation layer, 4 is the hydrogel substrate layer, 5 is the removable hydrogel interface layer, 6 is the polymer solution, 7 is the metal ion anchoring solution, and 8 is the metal chelating agent solution. Detailed Implementation

[0041] The principles and features of the present invention are described below with reference to the accompanying drawings and specific embodiments. The examples given are only for explaining the present invention and are not intended to limit the scope of the present invention.

[0042] Example 1

[0043] like Figure 1 and 2 As shown, this embodiment provides a chemically detachable hydrogel electrode for physiological electrophysiological measurements, comprising a flexible substrate layer 1, a flexible encapsulation layer 3, a flexible electrode array layer 2 integrating internal circuitry and one or more electrode points, a hydrogel substrate layer 4, a detachable hydrogel interface layer 5, and separately stored polymer solutions 6, metal ion anchoring solutions 7, and metal chelating agent solutions 8. The flexible substrate layer 1 and the flexible encapsulation layer 3 together form a flexible frame body. The flexible electrode array layer 2 is disposed within the flexible frame body. One or more electrode points extend out of the flexible frame body through windows on the flexible encapsulation layer 3. The hydrogel substrate layer 4 is disposed on the flexible encapsulation layer 3 and covers the electrode points. The detachable hydrogel interface layer 5 is detachably disposed on the hydrogel substrate layer 4 for adhesion to human tissue. The solute in the polymer solution is a water-soluble polymer containing carboxyl groups, and the metal anchoring solution is a metal cation / citric acid aqueous solution, wherein the metal cation is divalent or trivalent. The removable hydrogel interface layer 5 is bonded to and detached from the hydrogel base layer 4 through the polymer solution 6, the metal ion anchoring liquid 7, and the metal chelating agent solution 8.

[0044] In use, a polymer solution 6 and a metal ion anchoring solution 7 are used to form an anchoring network of metal cations and polymers on the hydrogel base layer 4 and the removable hydrogel interface layer 5, respectively. The two are anchored by external pressure. At the end of use, the anchoring network of metal cations and polymers is destroyed by soaking or dripping with a metal chelating agent solution 8, thereby removing the removable hydrogel interface layer 5.

[0045] During use, the metal cations in the hydrogel base layer 4 and the removable hydrogel interface layer 5 form metal chelate bonds with the carboxyl groups in the polymer, thus binding the two hydrogel layers together. After use, the hydrogel is soaked in a metal chelating agent solution 8. When the EDTANa4 solution 8 gradually penetrates into the interface layer of the two gels, the chelation between the metal cations and the ionic groups in the metal chelating agent solution 8 is stronger, and the chelation between the metal cations and the polymer is destroyed, thereby breaking the bond between the two hydrogel layers. The removable hydrogel interface layer 5 is then removed from the electrode.

[0046] The electrode of the present invention achieves the bonding and disassembly of the removable hydrogel interface layer 5 and the hydrogel base layer 4 by simply soaking in a chemical solution. Thus, the electrode can be reused by only replacing the removable hydrogel interface layer 5, which reduces costs and the risk of cross-infection.

[0047] Preferably, the polymer solution 6 contains a polymer mass fraction of 5wt%-10wt%; the metal ion anchoring solution 7 comprises a metal cation salt, citric acid, and water, with the pH adjusted to 2.7-3.3 using sodium hydroxide, wherein the mass fractions of the metal cation salt and citric acid range from 1wt%-4wt% and 1wt%-5wt%, respectively; and the metal chelating agent solution 8 comprises a metal chelating agent, acetic acid, and water, wherein the mass fractions of the metal chelating agent and acetic acid range from 5wt%-15wt% and 0.5wt%-2wt%, respectively.

[0048] The polymer is one or more selected from polyacrylic acid, hyaluronic acid, sodium alginate, polyaspartic acid, and carboxymethyl cellulose; the metal cation is Fe. 3+ Zr 4+ And Al 3+ One or more of the following; the metal chelating agent is EDTANa4.

[0049] Preferably, in this embodiment, the polymer is polyacrylic acid with a molecular weight of 100,000-240,000, and the metal cation is Fe. 3+ That is, the polymer solution is a polyacrylic acid solution, and the metal ion anchoring solution is Fe. 3+ / Citrate anchoring solution, the metal chelating agent solution is EDTANa4 solution.

[0050] The mass fraction of the polyacrylic acid solution is 5%; Fe 3+The formula for the citric acid anchoring solution is: 0.675g FeCl3·6H2O, 0.7875g C6H8O7·H2O, 20ml deionized water, and 4.1ml NaOH solution with a concentration of 0.1g / ml; the formula for the EDTANa4 solution is: 5g tetrasodium ethylenediaminetetraacetate, 50ml deionized water, and 1.7ml acetic acid with a mass percentage of 36%.

[0051] Preferably, the hydrogel base layer 4 and the removable hydrogel interface layer 5 contain a gel network formed by acrylamide polymerization.

[0052] Preferably, the hydrogel base layer 4 and the removable hydrogel interface layer 5 contain methacryloyloxyethyltrimethylammonium chloride (MATAC) microspheres, which can improve the anti-swelling and mechanical properties of the hydrogel base layer 4 and the removable hydrogel interface layer 5, thereby reducing their swelling rate during immersion in the solution.

[0053] Specifically, the preparation method of methacryloyloxyethyltrimethylammonium chloride (MATAC) microspheres is as follows:

[0054] S1. Dissolve 2-4 ml of 60wt%-80wt% methacryloyloxyethyltrimethylammonium chloride solution with a molecular weight of 207.7MW and 20-100 mg of MBAA in a beaker containing 50-100 ml of a mixed solution of deionized water and cyclohexane (water to cyclohexane mass ratio of 1:3). Stir magnetically for 15 min at a speed of 200-1000 r / min until the solution is homogeneous. Degas for 0.5-1 h to obtain methacryloyloxyethyltrimethylammonium chloride prepolymer solution.

[0055] S2. Add the prepolymer solution described above to a three-necked flask for emulsion polymerization, add 0.02-0.04 wt% KPS (potassium persulfate), stir thoroughly with a magnetic stirrer, and heat in a water bath to 50℃-80℃, with the magnetic stirrer rotating at 200-1000 r / min. After stirring magnetically for 2-5 hours, pour into a centrifuge tube, shake thoroughly with a shaker at 800 r / min for 10 minutes, and then set aside.

[0056] S3. The polymer washed by shaking above is centrifuged in a centrifuge (13000 rpm, 5-30 min) and then set aside for later use.

[0057] S4. Add the washed polymer to a freeze dryer and freeze dry thoroughly to obtain methacryloyloxyethyltrimethylammonium chloride (MATAC) microspheres.

[0058] Preferably, the hydrogel base layer 4 and the removable hydrogel interface layer 5 contain conductive materials.

[0059] Preferably, the conductive materials in the hydrogel base layer 4 and the removable hydrogel interface layer 5 can be independently selected from any one of LiCl, CaCl2, NaCl, PEDOT:PSS, polyaniline and polypyrrole. Adding conductive materials can make the two hydrogel layers have good conductivity.

[0060] Preferably, the removable hydrogel interface layer 5 contains dopamine-modified sodium alginate (Alg-DA), acrylic acid (AAC), and N-acryloyloxysuccinimide (AAC-NHS). Alg-DA can give the removable hydrogel interface layer 5 good adhesion, while AAC and AAC-NHS can increase its wet tack, enabling the removable hydrogel interface layer 5 to adhere stably to the tissue surface.

[0061] Specifically, the dopamine-modified sodium alginate (Alg-DA) described above can be prepared by the following method:

[0062] S1. Dissolve 10-20g of MES (2-morpholinoethanesulfonic acid) and 2-4g of NaCl in 500-1000ml of deionized water, then add 2-4ml of 0.1g / ml NaOH solution with a pH of 12-13 to obtain a MES solution with a pH of 5-6.

[0063] S2. Dissolve 1g-3g of Alg (sodium alginate) in 40-100ml of MES solution, then add 0.3g-0.8g of EDC (1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride), 0.2g-0.8g of NHS (N-hydroxysuccinimide), and 0.2g-0.8g of ascorbic acid. Stir at 200-600rpm for 20-60min to activate, then degas for 10-30min to prepare Alg solution for later use.

[0064] S3. Dissolve 0.2-0.8g of DA (dopamine hydrochloride) in 5-20ml of MES solution to prepare DA solution for later use.

[0065] S4. Pour the DA solution into a separatory funnel and then slowly add it to the Alg solution. Stir with a magnetic stirrer at 300 rpm for 6-24 hours.

[0066] S5. Dialyze the thoroughly stirred solution with deionized water for 48 hours, then freeze-dry it completely in a freeze dryer to obtain Alg-DA.

[0067] Preferably, the internal circuit is branched, with multiple electrode points located at the ends of the branches of the internal circuit. The hydrogel substrate 4 is divided into multiple non-connected regions corresponding to each of the electrode points, each covering the corresponding electrode point. The removable hydrogel interface layer 5 includes multiple non-connected regions, each corresponding to and bonded to multiple regions of the hydrogel substrate 4.

[0068] Preferably, the precursor solution of the hydrogel substrate layer 4 is composed of the following components: acrylamide (AM), LiCl, D-sorbitol, α-ketoglutarate, MABA crosslinking agent (N,N'-methylenebisacrylamide), sodium alginate, MATAC (methacryloyloxyethyltrimethylammonium chloride) microspheres, and deionized water. The mass fractions of acrylamide (AM), LiCl, D-sorbitol, α-ketoglutarate, MABA crosslinking agent (N,N'-methylenebisacrylamide), sodium alginate, and MATAC microspheres are 10-20 wt%, 1-5 wt%, 25-45 wt%, 0.1-0.5 wt%, 0.01-0.05 wt%, 0.1-0.5 wt%, and 0.5-3 wt%, respectively, with the balance being water.

[0069] Preferably, the precursor solution of the removable hydrogel interface layer 5 is composed of the following components: acrylamide (AM), dopamine-modified sodium alginate (Alg-DA), α-ketoglutarate, N,N'-methylenebisacrylamide (MBAA crosslinking agent), PEDOT:PSS, acrylic acid (AAC), N-acryloyloxysuccinimide (AAC-NHS), methacryloyloxyethyltrimethylammonium chloride (MATAC) microspheres, and deionized water. The mass fractions of acrylamide (AM), dopamine-modified sodium alginate (Alg-DA), α-ketoglutaric acid, N,N'-methylenebisacrylamide (MBAA crosslinking agent), PEDOT:PSS, acrylic acid (AAC), N-acryloyloxysuccinimide (AAC-NHS), and methacryloyloxyethyltrimethylammonium chloride (MATAC) microspheres are 10-20 wt%, 0.5-2.5 wt%, 0.1-0.5 wt%, 0.01-0.05 wt%, 3-15 wt%, 1-8 wt%, 0.1-0.8 wt%, and 0.5-3 wt%, respectively, with the balance being water.

[0070] Preferably, both the flexible substrate layer 1 and the flexible encapsulation layer 3 are made of polydimethylsiloxane (PDMS).

[0071] Preferably, the material of the flexible electrode array layer 2 is an ECC conductive composite material.

[0072] The ECC conductive composite material is composed of nano silver powder and PDMS in a mass ratio of 3:1. The above material is printed on a flexible substrate layer 1 and dried in a vacuum drying oven at 140-180℃ for 30-90 minutes to obtain the flexible electrode array layer 2.

[0073] Example 2

[0074] like Figure 3 and 4 As shown, this embodiment provides a method for using the above-mentioned chemically detachable hydrogel electrode for physiological electrometry, including the following steps:

[0075] 1) Before use, such as Figure 3 As shown in ④, ⑤, ⑥ and ⑦, the polymer solution 6 is added to the side of the hydrogel base layer 4 and the removable hydrogel interface layer 5 that need to be bonded, so that the polymer diffuses to form a polymer network. Then, metal ion anchoring liquid 7 is added to form an anchoring network between metal cations and polymer. Then, the two hydrogel layers that need to be bonded are placed side by side and squeezed for a certain period of time to bond the hydrogel base layer 4 and the removable hydrogel interface layer 5 together.

[0076] 2) The removable hydrogel interface layer 5 is adhered to human tissue for physiological electrical measurements;

[0077] 3) After use, if Figure 4 As shown in ① and ②, the metal chelating agent solution 8 is soaked in the removable hydrogel interface layer 5, and the metal chelating agent solution 8 does not exceed the bonding surface of the two hydrogel layers. After soaking for a certain period of time, the hydrogel base layer 4 and the removable hydrogel interface layer 5 can be separated.

[0078] 4) Soak the hydrogel base layer 4 in deionized water for a certain period of time to remove residual metal chelating agents;

[0079] 5) When using it again, replace the hydrogel interface layer and repeat steps 1-4 above.

[0080] In step 1), a polymer solution 6 is dropped onto the side of the hydrogel base layer 4 that needs to be bonded to the removable hydrogel interface layer 5, and allowed to diffuse completely. Then, a metal ion anchoring solution 7 is dropped on and allowed to diffuse completely. The removable hydrogel interface layer 5 is treated in the same way. Then, the removable hydrogel interface layer 5 is bonded to the hydrogel base layer 4, and a certain opposing compressive force is applied. Specifically, weights, presses, etc. can be used, and the lamination conditions are lamination under a pressure of 5-10N for 0.5-1h.

[0081] Preferably, based on the volume of the gel, every 2-16 cm³ 2 The amount of polymer solution 6 added to the gel was 1 ml, and the amount of metal ion anchoring solution added was 1 ml.

[0082] Preferably, the standing time after adding 6 drops of the polymer solution is 30 minutes, and the standing time after adding 7 drops of the metal ion anchoring solution is 30 minutes.

[0083] In step 3), you can either place the electrode upside down in the metal chelating agent solution 8, or you can drop the metal chelating agent solution 8 onto the removable hydrogel interface layer 5 for immersion.

[0084] Specifically, when choosing the inverted soaking method, the soaking time is 3-6 hours, specifically 6 hours in this embodiment; when choosing the drip soaking method, the soaking time is 3-6 hours, specifically 6 hours in this embodiment.

[0085] The soaking time in step 4) is 5-20 minutes, and in this embodiment it is 10 minutes.

[0086] Example 3

[0087] like Figure 3 As shown, this embodiment provides a method for preparing the above-mentioned chemically detachable hydrogel electrode for physiological electrometry, including the following steps:

[0088] S1. Prepare methacryloyloxyethyltrimethylammonium chloride microspheres, dopamine-modified sodium alginate, benzophenone solution, polymer solution 6, metal ion anchoring solution 7, and metal chelating agent solution 8, respectively.

[0089] S2. Precursor solutions for hydrogel base layer 4 and removable hydrogel interface layer 5 are prepared separately: Acrylamide, LiCl, D-sorbitol, and sodium alginate are dissolved in deionized water, then a photoinitiator and crosslinking agent are added, followed by the addition of methacryloyloxyethyltrimethylammonium chloride microspheres. After mechanical stirring for a certain time, the precursor solution for hydrogel base layer 4 is prepared; Acrylamide, dopamine-modified sodium alginate, PEDOT:PSS, acrylic acid, and N-acryloyloxysuccinimide are dissolved in deionized water, then a photoinitiator and crosslinking agent are added, and finally methacryloyloxyethyltrimethylammonium chloride microspheres are added. After mechanical stirring for a certain time, the precursor solution for removable hydrogel interface layer 5 is prepared.

[0090] S3. Fabrication of a flexible substrate layer 1, a flexible electrode array layer 2, and a flexible encapsulation layer 3, specifically including... Figure 3In the process: ① The ECC conductive composite material is screen-printed onto the prepared flexible substrate 1 and dried at 160°C for 1 hour to bond the flexible electrode array layer 2 onto the flexible substrate 1; the flexible encapsulation layer 3 is then bonded onto the flexible substrate. Double-sided tape or other adhesives can be used. In this embodiment, since PDMS is used as the material for both the flexible substrate 1 and the flexible encapsulation layer 3, uncured PDMS can be brushed between the flexible substrate 1 and the flexible encapsulation layer 3 and then dried at 70°C for 30 minutes to cure the PDMS and bond the flexible substrate 1 and the flexible encapsulation layer 3 together.

[0091] S4. Soak the area around the electrode point at the end of each branch of the flexible electrode array layer 2 in benzophenone solution for a certain period of time;

[0092] S5. The precursor solution of the hydrogel substrate layer 4 is cast into the electrode points at the ends of each branch of the flexible electrode array layer 2 through a mold. After irradiation with ultraviolet light for 45 minutes, the hydrogel substrate layer 4 solidifies and polymerizes at the electrode points, as detailed below. Figure 3 As shown in ③, the precursor solution of the removable hydrogel interface layer 5 is poured into a mold of the same shape, and after being irradiated with ultraviolet light, the hydrogel of the removable hydrogel interface layer 5 is polymerized.

[0093] Preferably, the photoinitiator is α-ketoglutaric acid, and the crosslinking agent is N,N'-methylenebisacrylamide.

[0094] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A chemically detachable hydrogel electrode for physiological electrical measurements, characterized in that, The flexible electrode array layer (2) integrated with inner circuit and one or more electrode points, the hydrogel base layer (4), the detachable hydrogel interface layer (5) and the separately stored high polymer solution (6), metal ion anchoring solution (7) and metal chelator solution (8); The flexible base layer (1) and the flexible packaging layer (3) together form a flexible frame body, the flexible electrode array layer (2) is arranged in the flexible frame body, one or more electrode points are arranged on the flexible packaging layer (3) and extend out of the flexible frame body through the window on the flexible packaging layer (3), the hydrogel base layer (4) is arranged on the flexible packaging layer (3) and covers the electrode points, and the detachable hydrogel interface layer (5) is detachably arranged on the hydrogel base layer (4) and used for adhering to human tissues. The solute in the high polymer solution (6) is a water-soluble high polymer containing carboxyl, the metal ion anchoring solution (7) is a metal cation / citric acid aqueous solution, and the metal cation is divalent or trivalent. The detachable hydrogel interface layer (5) is combined with and detached from the hydrogel base layer (4) through the high polymer solution (6), the metal ion anchoring solution (7) and the metal chelator solution (8).

2. The chemically detachable hydrogel electrode for physiological electrical measurement according to claim 1, wherein The mass fraction of the high polymer solution (6) is 2wt%-10wt%; The metal ion anchoring solution (7) comprises metal cation salt, citric acid and water, the pH is adjusted to 2.7-3.3 by using sodium hydroxide, and the mass fractions of the metal cation salt and the citric acid are 1wt%-4wt% and 1wt%-5wt%, respectively. The metal chelator solution (8) comprises metal chelator, acetic acid and water, and the mass fractions of the metal chelator and the acetic acid are 5wt%-15wt% and 0.5wt%-2wt%, respectively.

3. The chemically detachable hydrogel electrode for physiological electrical measurement according to claim 1 or 2, characterized by, The high molecular polymer is one or more of polyacrylic acid, hyaluronic acid, sodium alginate, polyaspartic acid, and carboxymethyl cellulose; the metal cation is one or more of Fe 3+ , Zr 4+ , and Al 3+ ; and the metal chelator is EDTANa4.

4. The chemically detachable hydrogel electrode for physiological electrical measurement according to claim 1, wherein The hydrogel base layer (4) and the detachable hydrogel interface layer (5) contain methacryloyloxyethyl trimethyl ammonium chloride microspheres.

5. The chemically detachable hydrogel electrode for physiological electrical measurement according to claim 4, characterized by, The hydrogel base layer (4) and the detachable hydrogel interface layer (5) contain conductive materials.

6. The chemically detachable hydrogel electrode for physiological electrical measurement according to claim 5, wherein The conductive materials in the hydrogel base layer (4) and the detachable hydrogel interface layer (5) can be independently selected from any one of LiCl, CaCl2, NaCl, PEDOT:PSS, polyaniline and polypyrrole.

7. The chemically detachable hydrogel electrode for physiological electrical measurement according to claim 6, wherein The detachable hydrogel interface layer (5) contains dopamine-modified sodium alginate, acrylic acid and N-acryloyloxy succinimide.

8. The chemically detachable hydrogel electrode for physiological electrical measurement according to claim 1, wherein The inner circuit is branched, a plurality of electrode points are arranged at the branch ends of the inner circuit, the hydrogel base layer (4) is divided into a plurality of regions corresponding to the electrode points and not connected to each other, and the detachable hydrogel interface layer (5) comprises a plurality of regions corresponding to the regions of the hydrogel base layer (4) and bonded thereto.

9. The method of using a chemically detachable hydrogel electrode for physiological electrical measurements according to any one of claims 1-8, characterized in that, The method comprises the following steps: 1) Before use, the high polymer solution is respectively added to the hydrogel base layer (4) and the detachable hydrogel interface layer (5) on the side needed to be combined to make the high polymer diffuse and form a high polymer network, then the metal ion anchoring solution is added to form an anchoring network of metal cations and high polymers, and then the two layers of hydrogel are placed opposite to each other on the side needed to be combined and extruded for a certain period of time, so that the hydrogel base layer (4) and the detachable hydrogel interface layer (5) are combined together; 2) The detachable hydrogel interface layer (5) is adhered to the human tissue to perform physiological electrical measurement; 3) After use, the detachable hydrogel interface layer (5) is soaked in the metal chelating agent solution, and the metal chelating agent solution does not exceed the combined surface of the two layers of hydrogel, and after soaking for a certain period of time, the hydrogel base layer (4) and the detachable hydrogel interface layer (5) can be separated; 4) The hydrogel base layer (4) is soaked in deionized water for a certain period of time to remove the residual metal chelating agent; 5) When used again, a new hydrogel interface layer (5) is replaced, and the above steps 1)-4) are repeated.

10. The method for preparing a chemically detachable hydrogel electrode for physiological electrical measurement according to claim 7, characterized by, Comprising the following steps: S1. Prepare methyl methacryloyloxyethyl trimethyl ammonium chloride microspheres, dopamine-modified sodium alginate, benzophenone solution, high polymer solution (6), metal ion anchoring solution (7), and metal chelating agent solution (8) respectively; S2. Prepare precursor solutions of the hydrogel base layer (4) and the detachable hydrogel interface layer (5) respectively: dissolve acrylamide, LiCl, D-sorbitol, and sodium alginate in deionized water, then add a photoinitiator and a crosslinking agent, and then add methyl methacryloyloxyethyl trimethyl ammonium chloride microspheres, and mechanically stir for a certain period of time to prepare the precursor solution of the hydrogel base layer (4); dissolve acrylamide, dopamine-modified sodium alginate, PEDOT:PSS, acrylic acid, and N-acryloyloxysuccinimide in deionized water, then add a photoinitiator and a crosslinking agent, and finally add methyl methacryloyloxyethyl trimethyl ammonium chloride microspheres, and mechanically stir for a certain period of time to prepare the precursor solution of the detachable hydrogel interface layer (5); S3. Prepare a flexible base layer (1), a flexible electrode array layer (2), and a flexible packaging layer (3); S4. Soak the area around the electrode points at the ends of each branch of the flexible electrode array layer (2) in the benzophenone solution for a certain period of time; S5. Pour the precursor solution of the hydrogel base layer (4) onto the electrode points at the ends of each branch of the flexible electrode array layer (2) through a mold, and after irradiation with ultraviolet light, the hydrogel base layer (4) is polymerized on the electrode points, and the precursor solution of the detachable hydrogel interface layer (5) is poured into the same shape mold, and after irradiation with ultraviolet light, the hydrogel of the detachable hydrogel interface layer (5) is polymerized.

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