Composite membranes, their manufacturing methods, applications, and biosensors

Abstract

This invention relates to the hydrogel technology field and specifically provides a composite membrane, its manufacturing method, applications, and a biosensor. The composite membrane includes a hydrogel-based membrane, within which a reinforcing rib layer is embedded. The reinforcing rib layer is positioned along the extension direction of the hydrogel-based membrane, and the reinforcing rib layer contains some fibers, the fiber material being an elastic polymer, and the thickness of the reinforcing rib layer is 0.1 to 4.0 μm. The mechanical reinforcement between the reinforcing rib layer and the hydrogel-based membrane significantly improves the mechanical properties of the composite membrane, such as tensile strength, toughness, and strength. At the same time, the composite membrane achieves a balance between thickness and mechanical properties, resulting in an ultra-thin structure, good mechanical properties, and breathability, enabling long-term, continuous monitoring of human health using a composite membrane electronic skin biosensor.

Description

[Technical Field]

[0001] This application belongs to the field of hydrogel technology and specifically provides composite membranes, methods for producing the same, applications, and biosensors. [Background technology]

[0002] Long-term, continuous monitoring of the human body's electrophysiological signals, such as electrocardiograms, electromyograms, and electroencephalograms, is crucial for disease prevention, early detection, diagnosis, and treatment. Many instruments and devices that monitor physiological electrical signals require establishing a certain connection between biological tissue and electronic systems. However, the inherent differences between soft biological tissue and rigid electronic components significantly impact the compatibility, effectiveness, and stability of the interface between biological tissue and electronic systems.

[0003] Hydrogels are similar to biological tissues and possess electrical, mechanical, and biological properties that mimic those of biological tissues, making them one of the ideal materials for next-generation bioelectronic interfaces, providing an effective interface between biological tissues and electronic systems. In recent years, hydrogels have made significant progress in the development of flexible wearable sensors. However, hydrogels have problems such as the incompatibility of thinness and mechanical properties, susceptibility to dehydration, and poor gas diffusion, which are major constraints on their application in long-term, continuous monitoring of human physiological health.

[0004] To reduce the thickness of hydrogel films, one conventional technique involves researchers producing a 150 μm thick hydrogel film by die casting. However, the hydrogel films produced by this method have poor permeability and mechanical properties, are prone to fracture during the transition process, and cannot withstand the dynamic environment of human skin for extended periods. Another conventional technique involves researchers using a simple double-roller coating machine to extrude a hydrogel coated between two layers of hydrophobic film, obtaining an ultrathin hydrogel with adjustable thickness and peelable film layers. However, the hydrogel films produced by this method also suffer from similar problems with poor mechanical properties. [Overview of the project]

[0005] The purpose of this application is to provide a composite membrane, a method for manufacturing the same, and applications that solve the problem of the inferior mechanical properties of conventional ultrathin hydrogels. Furthermore, this application provides a biosensor that can be used for long-term, continuous monitoring of human health.

[0006] In the first embodiment, a composite film is provided. The composite film includes a hydrogel-based film, in which a reinforcing rib layer is embedded, and the reinforcing rib layer is positioned along the extending direction of the hydrogel-based film. The reinforcing rib layer contains some fibers, and the fiber material contains an elastic polymer. The thickness of the reinforcing rib layer is 0.1 to 4.0 μm.

[0007] In the composite film according to the embodiment of the present invention, the reinforcing rib layer, which is installed along the extension direction of the hydrogel base film, greatly improves the mechanical properties of the composite film, including, for example, tensile strength, toughness, and strength, through interaction between the reinforcing rib layer and the hydrogel base film. Furthermore, by controlling the fibrous material and thickness of the reinforcing rib layer, the reinforcing rib layer and the hydrogel base film interact with each other, performing a mechanical strengthening effect, thereby imparting an ultra-thin structure to the composite film and giving it excellent mechanical properties. Moreover, because the hydrogel base film is thin, the composite film has good permeability.

[0008] In a second aspect, the present invention provides a method for manufacturing a composite film. The manufacturing method is as follows: A step of providing a hydrogel solution and reinforcing ribs, A process to deposit a hydrogel solution and reinforcing ribs to obtain a liquid hydrogel composite film, and the reinforcing ribs to form a reinforcing rib layer in the hydrogel composite film. The process includes a step of gelling a hydrogel composite membrane to manufacture a composite membrane, The reinforcing rib layer contains some fibers, and the fiber material contains an elastic polymer. The thickness of the reinforcing rib layer is 0.1 to 4.0 μm.

[0009] The liquid hydrogel composite film manufactured by the manufacturing method of the composite film according to the embodiment of the present invention contains a liquid hydrogel film layer, and the reinforcing rib layer is installed along the extending direction of the liquid hydrogel film layer. The liquid hydrogel composite film is subjected to a gelation treatment, which gels the hydrogel solution in the liquid hydrogel film layer, converting it from a liquid to a gel state to form a hydrogel base film, and a composite film structure is formed in which the reinforcing rib layer is embedded in the hydrogel base film. In the composite film manufactured by this manufacturing method, the relationship between the hydrogel base film and the reinforcing rib layer provides a strengthening effect on the film layer mechanics, and the composite film has an ultra-thin structure while possessing good mechanical properties. Furthermore, since the manufacturing method according to the present invention reduces the thickness of the composite film while ensuring mechanical properties, the permeability of the composite film is also improved. Moreover, since the reinforcing rib layer is easily installed within the hydrogel solution film layer, this manufacturing method has fewer steps, is easy to control process conditions, and produces mass-produced products with uniform quality, good quality reproducibility and stability.

[0010] In a third aspect, the present invention provides applications of the composite film according to the present invention in biosensors, electronic skin, and flexible electronic devices.

[0011] The composite membrane according to the embodiment of this invention has advantages such as a thin membrane layer, good mechanical properties, and excellent breathability. Therefore, when the composite membrane is applied to biosensors, electronic skin, and flexible electronic devices, it offers good stability, high comfort, and is suitable for long-term, continuous use.

[0012] In a fourth embodiment, the present invention provides a biosensor comprising a composite membrane according to the above embodiment.

[0013] The biosensor according to the embodiment of the present application connects the electronic system and the biological tissue through the composite membrane. Since the composite membrane has mechanical properties such as good flexibility and tensile performance, the compatibility between the composite membrane and the biological tissue is improved, and the stability of the interface between the biosensor and the biological tissue is improved. Since the composite membrane further has a thin thickness and good air permeability, the comfort of using the biosensor is improved.

Brief Description of Drawings

[0014] To more clearly explain the specific embodiments of the present application or the technical solutions in the prior art, the drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the following drawings are some embodiments of the present application. For those skilled in the art, other drawings can be obtained from these drawings on the premise of no creative work. [Figure 1] It is a schematic diagram of the structure of the composite membrane according to the embodiment of the present application. [Figure 2] It is a flowchart of the manufacturing method of the composite membrane according to the embodiment of the present application. [Figure 3] It is a flowchart of the manufacturing of the composite membrane according to Example 1. [Figure 4] It is a SEM image of the nanomesh according to Example 3. [Figure 5] It is a SEM image of the composite membrane according to Example 1 after freeze-drying. [Figure 6] It is a schematic diagram of the skin compatibility test result of the composite membrane according to Example 1. [Figure 7] It is a SEM image of the thickness of the composite membrane according to Examples 1 to 3. [Figure 8] It is a schematic diagram of the thickness measurement result of the composite membrane according to Examples 1 to 3 and the hydrogel-based membrane according to Comparative Example 1. [Figure 9] It is a schematic diagram of the tensile performance test results of the composite membrane according to Examples 1 to 3, the hydrogel-based membrane according to Comparative Example 1, and the reinforcing rib according to Example 1. [Figure 10] It is a schematic diagram of the anti-drying property measurement result of the composite membrane according to Example 1 and Example 12. [Figure 11]This is a schematic diagram of the results of the air permeability measurement of the composite membrane according to Example 1. [Figure 12] This is a schematic diagram showing the results of measuring the adhesiveness per unit area of ​​the composite films according to Examples 1 to 3. [Figure 13] This is a schematic diagram of electrocardiogram signal monitoring between a composite membrane and commercial gel according to Example 1, where A is a schematic diagram of the skin contact impedance result, B is a schematic diagram of the monitoring site, C is a schematic diagram of the electrocardiogram signal monitoring result between the commercial electrode and the composite membrane, D is a schematic diagram of the electrocardiogram signal monitoring result at different time points of continuous monitoring of the composite membrane, and E is a schematic diagram of the signal-to-noise ratio of the electrocardiogram monitoring between the commercial electrode and the composite membrane. [Figure 14] This is a schematic diagram of electromyography (EMG) signal monitoring of a composite membrane and commercial gel according to Example 1, where A is a schematic diagram of the monitoring site and B is a schematic diagram of the EMG signal monitoring results. [Figure 15] This is a schematic diagram of electromyography (EMG) signal monitoring induced by stimulation. A is a schematic diagram of the stimulation site and the monitoring site, and B is a schematic diagram of the EMG signal monitoring results induced by stimulation. [Figure 16] This is a schematic diagram of electrooculography (ECO) monitoring, where A is a schematic diagram of the monitoring site and B is a schematic diagram of the EOCTOC monitoring results. [Figure 17] This is a schematic diagram of electroencephalogram (EEG) signal monitoring, where A is a schematic diagram of the monitoring area and B is a schematic diagram of the EEG signal monitoring results. [Modes for carrying out the invention]

[0015] To further clarify the technical problems, technical solutions, and beneficial effects that this application aims to solve, the present application will be described in more detail below with reference to examples. The specific examples described are for interpreting this application and are not intended to limit it.

[0016] In this application, the terms "and / or" describe the relationship between related objects, indicating that three relationships are possible. For example, A and / or B can represent the case where A exists alone, where A and B exist simultaneously, or where B exists alone. A and B may be singular or plural. The symbol " / " generally indicates that the preceding and succeeding related objects have an "or" relationship.

[0017] In this application, "at least one" means one or more. "Multiple" means two or more. "At least one of the following" or similar expression means any combination of these items, including any combination of single or multiple items. For example, "at least one of a, b, or c" or "at least one of a, b, or c" can both refer to a, b, c, ab (i.e., a and b), ac, bc, or abc, and a, b, and c may be single or multiple.

[0018] As should be understood, in each embodiment of the present invention, the magnitude of the number of each process does not indicate the execution order, some or all of the steps may be executed in parallel or sequentially, and the execution order of each process is determined by its function and inherent logic, and does not limit the execution process of the embodiments of the present invention in any way.

[0019] The terms used in the embodiments of this application are for the purpose of describing specific embodiments and are not intended to limit this application. Unless otherwise specified, the singular forms “one type,” “the foregoing,” and “the” used in the embodiments of this application and the attached claims also include the plural forms.

[0020] The weight of the relevant components described in the examples of this specification refers not only to the specific content of each component but also to the proportional relationship in weight between each component. Therefore, any expansion or contraction of the content of the relevant components in the examples of this specification due to proportionality falls within the scope of disclosure of the examples of this specification. Specifically, the mass described in the examples of this specification may be in mass units known in the chemical industry, such as μg, mg, g, or kg.

[0021] Hydrogels are widely used in medical devices because they possess tissue-like flexibility, natural biocompatibility, toughness, and ionic conductivity, serving as interfaces connecting electronic systems and biological tissues. However, thin films manufactured from current hydrogels suffer from technical challenges such as an inability to balance thickness and mechanical properties, and poor air permeability. This results in poor interface stability, severely limiting the application of hydrogels in long-term biological signal monitoring. To overcome these shortcomings in current hydrogels, this application provides the following example solution.

[0022] In a first embodiment, the present invention provides a composite film. In some embodiments, the structure of the composite film according to the present invention is shown in Figure 1 and includes a hydrogel-based film 1, in which a reinforcing rib layer 2 is embedded, and the reinforcing rib layer 2 is positioned along the extending direction of the hydrogel-based film 1. The reinforcing rib layer 2 contains some fibers, and the fiber material contains an elastic polymer. The thickness of the reinforcing rib layer 2 is 0.1 to 4.0 μm.

[0023] In the composite film according to the embodiment of the present invention, a reinforcing rib layer 2 is installed along the extending direction of the hydrogel base film 1, and the mechanical strength of the composite film is improved by the interaction between the hydrogel base film 1 and the reinforcing rib layer 2. Furthermore, by controlling the fibrous material of the reinforcing rib layer 2 and the thickness of the reinforcing rib layer within a specific range, the composite film according to the embodiment of the present invention has an ultra-thin structure and good mechanical properties.

[0024] Note that the thickness of the reinforcing rib layer 2 refers to the thickness along the thickness direction of the composite film of the reinforcing rib layer 2.

[0025] In some embodiments, the thickness of the reinforcing rib layer 2 may be typical thicknesses such as 0.2 μm, 0.6 μm, 1.1 μm, 1.5 μm, 1.8 μm, 2.0 μm, 2.5 μm, 3.0 μm, 3.5 μm, and 4.0 μm, but is not limited to these. By controlling the thickness of the reinforcing rib layer 2 within this range, the composite film forms an ultrathin structure and has good mechanical properties.

[0026] In some embodiments, the fibers in the reinforcing rib layer 2 may be intertwined to form a network structure. In some other embodiments, the fibers in the reinforcing rib layer 2 may be parallel to each other and not in contact with each other; for example, the fibers in the reinforcing rib layer 2 may be parallel to each other or arranged spirally in the same plane.

[0027] In some embodiments, the morphology of the mesh structure formed by the intertwining of fibers may be regular or irregular. For example, in some embodiments, the mesh structure may be a regular fishing net-like structure, a honeycomb-like structure, or an irregular nonwoven fabric structure. The reinforcing rib layer 2 is set to a mesh structure and embedded in the hydrogel base membrane 1. The interaction between the reinforcing rib layer 2 and the hydrogel base membrane 1 improves the tensile strength and tensile performance of the composite membrane, effectively reducing the tendency for the hydrogel base membrane 1 to break when pulled individually.

[0028] In some embodiments, the mesh structure of the reinforcing rib layer 2 may be a single layer or multiple layers. In further embodiments, if the mesh structure of the reinforcing rib layer 2 is multiple layers, the multiple layers may be independent of each other, connected to each other, or intertwined.

[0029] In some embodiments, the diameter of a single fiber may be 180 to 1600 nm, and further, the diameter of a single fiber may be 200 to 1500 nm. In specific examples, the diameter of the fiber may be typical diameters such as 200 nm, 250 nm, 300 nm, 350 nm, 400 nm, 450 nm, 500 nm, 650 nm, 700 nm, 750 nm, 800 nm, 850 nm, 900 nm, 950 nm, 1000 nm, 1100 nm, 1200 nm, 1300 nm, 1400 nm, 1500 nm, etc., but not limited thereto. By controlling the diameter of the fiber within this range, the thickness of the reinforcing rib layer 2 is reduced, and the thickness of the composite film is further reduced. Further, by controlling the diameter of the fiber, the reinforcing rib layer 2 has better mechanical properties such as toughness and elasticity, and further improves the mechanical properties such as flexibility and tensile performance of the composite film. Note that the diameter of the fiber according to the embodiments of the present application refers to the average diameter of the fiber. For example, the fiber having a diameter of 800 nm to 1000 nm means that the average diameter of the fibers in the reinforcing rib layer 2 is within the range of 800 nm to 1000 nm, and not all the diameters of the fibers in the reinforcing rib layer 2 are within the range of 800 nm to 1000 nm.

[0030] In some embodiments, the density of the reinforcing rib layer 2 is 0.1 to 3.6 mg / cm 2 , 2 , 2 , 2 , 2 , 2 , 2 , 2 , 2 , 2 , 2 and may be. In further embodiments, the density of the reinforcing rib layer 2 is 0.2 to 1.0 mg / cm 2 and may be. In specific examples, the density of the reinforcing rib layer 2 is 0.1 mg / cm 2 , 0.2 mg / cm 2 , 0.3 mg / cm 2 , 0.35 mg / cm 2 , 0.4 mg / cm 2 , 0.5 mg / cm 2 , 0.6 mg / cm 2 , 0.8 mg / cm 2 , 1.0 mg / cm 2 , 2.0 mg / cm 2 , 3.0 mg / cm 2 , 3.6 mg / cm 2Typical densities such as those listed above are acceptable, but are not limited to them. By controlling the density of the reinforcing rib layer 2 within this range, the balance between the elasticity and strength of the reinforcing rib layer 2 can be further improved, resulting in the reinforcing rib layer 2 having good elasticity and appropriate strength, further improving the tensile performance of the composite film, and the composite film having high strength.

[0031] In some examples, the elastic polymers include polyurethane (Thermoplastic Polyurethane, TPU), styrene-butadiene-styrene elastic materials (Styrene Block Copolymers, SBS), hydrogenated styrene-butadiene block copolymers (Styrene Ethylene Butylene Styrene, SEBS), polyethylene terephthalate (PET), poly(lactic-co-glycolic acid, PLGA), polyethyleneimine (Poly(ethylenimine, PI), and polyvinylidene fluoride (Poly(vinylidene It may contain at least one of fluoride or PVDF. These polymer materials have good elasticity and toughness, and the formed fibers have good toughness and flexibility, making them resistant to breakage when pulled. The reinforcing rib layer 2 effectively interacts with the hydrogel base film 1, improving the tensile performance and flexibility of the composite film. The material of these fibers may be a single polymer compound or may contain multiple polymer compounds, for example, TPU and SBS, and can be specifically adjusted according to actual needs.

[0032] In some embodiments, the hydrogel-based membrane 1 may contain water and a substrate. The substrate may be a temperature-reversible substance, and the aqueous solution of the substrate may be in a well-flowing solution state, and at the usage or storage temperature, the aqueous solution of the substrate may be a warm gel. Of course, the aqueous solution of the substrate may be liquid at high temperatures (e.g., liquid at temperatures above 50°C) and gel-like at low temperatures (e.g., gel-like at temperatures below 50°C).

[0033] In further embodiments, the substrate may include at least one of gelatin, carrageenan, locust bean gum, or guar gum. Hydrogels composed of these substrates are gel-like at room temperature and at temperatures close to body temperature. As a result, when the composite membrane is applied to electronic skin, biosensors, physiological electrical signaling devices (e.g., electrocardiographs), and under storage conditions, the hydrogel-based membrane 1 can maintain a stable gel state without liquefaction, thus maintaining the morphological stability of the composite membrane. Of course, the substrate may contain only one compound, such as gelatin, or multiple compounds, such as gelatin and carrageenan, and can be specifically adjusted according to actual needs. Furthermore, these substrates give the hydrogel-based membrane 1 a microporous structure, and the composite membrane has good permeability.

[0034] In some embodiments, the substrate may contain gelatin, and may also contain type A gelatin. Type A gelatin has high transparency, which results in a composite film with good transparency, and the aqueous solution of type A gelatin has good fluidity, which can further improve the uniformity of the film layer thickness of the composite film.

[0035] In some embodiments, if the mass of the hydrogel-based membrane 1 is taken as 100%, the substrate content in the hydrogel-based membrane 1 may be 2-15%. In further embodiments, the substrate content may be 5-10%. In specific embodiments, the substrate content may be typical content such as 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, and 15%, but is not limited to these. By controlling the substrate content in the hydrogel-based membrane 1 within this range, the hydrogel-based membrane 1 has an appropriate modulus, the structural stability of the hydrogel-based membrane 1 in the composite membrane is improved, the hydrogel-based membrane 1 and the reinforcing rib layer 2 are difficult to separate, and the composite membrane has good flexibility.

[0036] In some embodiments, the hydrogel-based membrane 1 may further contain a water-retaining agent. In further embodiments, the mass content of the water-retaining agent may be 0-30% when the mass of the hydrogel-based membrane 1 is 100%. In even further embodiments, the water-retaining agent content may be 20-30%. Typical contents may be, but are not limited to, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, and 30%. By adding a water-retaining agent and controlling the content of the water-retaining agent, the hydrogel-based membrane 1 is provided with long-term resistance to dehydration and drying.

[0037] In some embodiments, the water-retaining agent may include at least one of alcohol compounds, highly hydrated salts, and anionic surfactants. These water-retaining agents have good water retention properties and can effectively retain moisture in the hydrogel base membrane 1, preventing drying and dehydration of the hydrogel base membrane 1. Furthermore, these water-retaining agents are difficult to decompose and deactivate, possessing good stability and durability, and can retain moisture in the hydrogel base membrane 1 for a long period of time.

[0038] In some examples, the alcohol compound may include at least one of glycerin, ethylene glycol, 1,2-propylene glycol, and 1,3-propylene glycol. These alcohol compounds have a large number of hydrophilic groups such as hydroxyl groups and have good water retention properties. Furthermore, these alcohol compounds and water are soluble in each other or have high solubility in water, forming a stable two-solvent system with water, effectively reducing water loss from the hydrogel base film 1.

[0039] In some embodiments, the highly hydrated salt may contain lithium chloride, and the lithium chloride and the water in the hydrogel base membrane 1 form a highly hydrated product, which effectively retains the water in the hydrogel base membrane 1.

[0040] In some embodiments, the anionic surfactant may include belladonna oil.

[0041] In some embodiments, the hydrogel-based membrane 1 may further contain a crosslinking agent. The crosslinking agent may include at least one of sodium tetraborate, sodium citrate, and tannic acid. The addition of the crosslinking agent crosslinks the substrate molecules and the water-retaining agent molecules, improving the phase transition temperature of the hydrogel-based membrane 1 and the mechanical properties of the composite membrane. For example, in a specific example, sodium tetraborate may be used to crosslink glycerin and gelatin to increase the phase transition temperature, thereby allowing the aqueous solution of gelatin to convert to a gel state at a higher temperature. The hydrogel-based membrane 1 maintains a good gel state at the surface temperature of the human body (e.g., 37°C) and reduces the possibility of the hydrogel-based membrane 1 losing its gel state during use or storage.

[0042] In some embodiments, the mass content of the crosslinking agent may be 0-5% when the mass of the hydrogel base film 1 is taken as 100%. In further embodiments, the crosslinking agent content may be 3-4.5%. In specific examples, the crosslinking agent content may be typical content such as 1%, 2%, 3%, 3.5%, 4%, 4.5%, and 5%, but is not limited to these. By controlling the crosslinking agent content within this range, the phase transition temperature of the hydrogel can be improved, further reducing the possibility of the hydrogel base film losing its gel state during use, and reducing the possibility of excessive crosslinking between the substrate and molecules such as humectants in the hydrogel due to excessive addition of the crosslinking agent. This phenomenon of excessive crosslinking affects the tensile performance of the composite film. Therefore, the tensile performance of the composite film is further improved.

[0043] In some embodiments, the hydrogel-based membrane 1 may further contain a conductive agent. The addition of the conductive agent imparts conductivity to the hydrogel-based membrane 1, and further imparts conductivity to the composite membrane, thereby making the composite membrane applicable to bioelectric monitoring.

[0044] In some embodiments, the conductive agent may include a water-soluble ionic compound. In further embodiments, the conductive agent may include water-soluble sulfates, chlorides, and nitrates. In specific examples, the conductive agent may include at least one of sodium sulfate, sodium chloride, sodium nitrate, potassium sulfate, sodium acetate, potassium chloride, and potassium nitrate. The use of a water-soluble ionic compound conductive agent causes the conductive agent to dissociate in the hydrogel base film 1, resulting in a transparent state for the hydrogel base film 1, further reducing the amount of insoluble particles in the hydrogel base film 1, and further reducing the thickness of the hydrogel base film 1.

[0045] In some embodiments, the conductive agent may be a water-soluble sulfate. The sulfate group can improve the tensile performance of the hydrogel-based film 1 and further enhance the tensile performance of the composite film.

[0046] Of course, if the requirements for the light transmittance or transparency of the hydrogel-based film 1, the adhesive performance of the composite film, etc., are not high, the conductive agent may further contain nonionic conductive agents such as carbon nanotubes, graphite, or nanosilver powder.

[0047] In some embodiments, the mass content of the conductive agent may be 0-3% when the mass of the hydrogel base film 1 is considered 100%. Furthermore, the content of the conductive agent may be 1-3%. Specific examples may include typical content such as 1%, 1.2%, 1.4%, 1.6%, 1.8%, 2%, 2.2%, 2.4%, 2.6%, 2.8%, and 3%, but are not limited to these. By controlling the content of the conductive agent, the deposition of the conductive agent is avoided, thereby ensuring that the hydrogel base film 1 has good conductivity and reducing the influence of the conductive agent on the adhesive performance of the composite film.

[0048] In several examples, the reinforcing rib layer 2 and hydrogel base membrane 1, in each example, intertwined fibers in the reinforcing rib layer 2 in the composite membrane form a fiber network, with a fiber diameter of 900 nm and a density of 0.1 to 3.6 mg / cm³. 2The hydrogel-based membrane 1 in the composite membrane may contain a substrate in a content of 2-15%, a water-retaining agent in a content of 0-30%, a crosslinking agent in a content of 0-5%, and a conductive agent in a content of 0-3%. The substrate is gelatin, the water-retaining agent is glycerin, the crosslinking agent is sodium tetraborate, and the conductive agent is sodium sulfate.

[0049] In further embodiments, the density of the reinforcing rib layer 2 is 0.2 to 1.0 mg / cm³. 2 It is also possible that the content of the substrate in the hydrogel base film 1 is 5-10%, the content of the water-retaining agent is 20-30%, the content of the crosslinking agent is 3-4.5%, and the content of the conductive agent is 1-3%.

[0050] By controlling the fiber material, density, thickness, and morphology of the reinforcing rib layer 2, and controlling the content of each component in the hydrogel base membrane 1 within a specified range, the composite membrane retains good mechanical properties even with an ultra-thin thickness, and also possesses good breathability, water retention, and adhesion. As a result, when the composite membrane is applied, for example, to a biosensor, it has good skin compatibility and comfort. Furthermore, due to the long-term water retention of the composite membrane, it has long-term stability when used as an interface between biological tissue and electronic systems.

[0051] In some embodiments, the thickness of the composite film may be 10 to 200 μm. In further embodiments, the thickness of the composite film may be 10 to 40 μm. Specifically, the thickness of the composite film may be, but is not limited to, typical thickness ranges such as 10 μm, 12 μm, 15 μm, 18 μm, 20 μm, 25 μm, 30 μm, 35 μm, 40 μm, 50 μm, 60 μm, 70 μm, 80 μm, 90 μm, 100 μm, 150 μm, and 200 μm. Composite films within these thickness ranges further improve comfort during use and effectively avoid the feeling of weight during use.

[0052] In some examples, the permeability of the composite membrane was 0.1 to 3.0 kg m -2 d -1This may also be the case. In further examples, the permeability of the composite membrane is 1.8-2.7 kg m -2 d -1 That's fine.

[0053] In some embodiments, the tensile strength of the composite film may be 450% to 800%, or it may be 483% to 606%.

[0054] In several examples, by controlling the components in the hydrogel-based membrane of the composite membrane, the composite membrane exhibits good water retention. After storage of the composite membrane for 1 to 21 days, the water retention rate is 90% or higher. Furthermore, after storage of the composite membrane for 21 days, the water retention rate may exceed 99%. In specific examples, after storage of the composite membrane for 21 days, the water retention rate may be values ​​such as 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, and 100%.

[0055] The composite film also possesses good adhesion. In some examples, the adhesive strength per unit area of ​​the composite film is 20-200 μJ / cm². 2 In further embodiments, the tackiness per unit area of ​​the composite film is 58.3 to 177 μJ / cm². 2 That is the case.

[0056] Due to the composite membrane's excellent water retention and adhesive properties, it can establish a stable and lasting connection with the skin, improving the effectiveness and stability of the interface between physiological signal monitoring devices and the skin.

[0057] In a second embodiment, a method for manufacturing a composite film is provided. Referring to Figure 1, the process for manufacturing a composite film according to the embodiment of the present application is shown in Figure 2. The method for manufacturing a composite film according to the embodiment of the present application is: Step S01 provides a hydrogel solution and reinforcing ribs. Step S02 involves a film deposition process of the hydrogel solution and reinforcing ribs to obtain a liquid hydrogel composite film, and the reinforcing ribs forming a reinforcing rib layer in the hydrogel composite film. The process includes step S03, which involves gelling a hydrogel composite film to produce a composite film. The reinforcing rib layer contains some fibers, and the fiber material contains an elastic polymer. The thickness of the reinforcing rib layer is 0.1 to 4.0 μm.

[0058] In the manufacturing method according to the embodiment of this application, by forming a hydrogel solution and reinforcing ribs, the hydrogel solution forms a liquid hydrogel solution film layer, and the reinforcing ribs form a reinforcing rib layer 2 embedded in the hydrogel solution film layer, forming a liquid hydrogel composite film. Gelation converts the hydrogel solution film layer from a liquid state to a gel state, forming a hydrogel base film 1, forming a composite film, and embedding the reinforcing rib layer 2 within the hydrogel base film 1. In this composite film, a mechanical strengthening effect is performed between the reinforcing rib layer 2 and the hydrogel base film 1, thereby giving the composite film an ultrathin structure and good mechanical properties. Furthermore, the manufacturing method according to the embodiment of this application has fewer process steps, easy process conditions to control, high operability, facilitates mass production, and has excellent reproducibility of product quality.

[0059] Furthermore, the permeability of the composite membrane is related to the thickness of the hydrogel base membrane 1. All other conditions being equal, the thinner the hydrogel base membrane 1, the better the permeability of the composite membrane. Since the composite membrane can form an ultrathin structure with good mechanical properties, the hydrogel base membrane 1 in the composite membrane also has an ultrathin structure, and the composite membrane can have good permeability.

[0060] Step S01 The reinforcing ribs provided in step S01 are used to form the reinforcing rib layer 2 included in the composite film according to the embodiment of the present invention described above. The structure, material, form, and thickness of the reinforcing ribs are the same as those of the reinforcing rib layer 2 described above, and for simplicity, the structure and material of the reinforcing ribs will not be described again here.

[0061] In some embodiments, reinforcing ribs may be manufactured by electrospinning. The diameter of the fibers in the reinforcing ribs manufactured by this method can be adjusted according to the actual demand. Furthermore, the fibers manufactured by electrospinning have good uniformity in thickness, resulting in good uniformity of the manufactured reinforcing ribs and further improving the uniformity of the manufactured composite film. Of course, reinforcing ribs may also be manufactured by other methods, such as meltblowing.

[0062] The hydrogel solution obtained in step S01 is used to form the hydrogel base film 1 contained in the composite film according to the above embodiment of the present invention. The content of each component in the hydrogel solution is the same as the content of each component in the hydrogel base film 1 contained in the composite film according to the above embodiment of the present invention.

[0063] In some embodiments, the temperature of the hydrogel solution may be 50-80°C. By controlling the temperature of the hydrogel solution within this range, the hydrogel solution can be stably maintained in a liquid state, resulting in good film formation properties, contributing to the formation of a hydrogel solution film layer, and facilitating the placement of reinforcing ribs within the hydrogel film layer.

[0064] Step S02 In step S02, the hydrogel solution and reinforcing ribs are subjected to a film deposition process, forming a liquid hydrogel film layer with the hydrogel solution and a reinforcing rib layer 2 embedded within the liquid hydrogel film layer, thereby producing a liquid hydrogel composite film.

[0065] In some embodiments, in step S02, the hydrogel solution and reinforcing ribs may be subjected to film formation by methods such as immersion coating, spray coating, brush coating, or press molding. For example, in a specific example, if the reinforcing ribs are a nanofiber network and a liquid hydrogel film layer is formed by immersion coating, immersing the reinforcing ribs in the hydrogel solution and then removing them allows the hydrogel solution to form a liquid hydrogel film layer over the fiber network, and the reinforcing rib fiber network can form a reinforcing rib layer 2 embedded within the hydrogel base film layer. The hydrogel composite film formed by the immersion coating method can improve the uniformity of the thickness of the hydrogel film layers on both sides of the reinforcing rib layer 2 and further promote the uniform distribution of the hydrogel film layers on both sides of the reinforcing rib layer 2. Furthermore, the thickness of the hydrogel film layer may be adjusted by adjusting the diameter, thickness, network structure, and density of the fibers in the reinforcing rib layer 2.

[0066] Step S03 In step S03, the liquid hydrogel composite membrane produced in step S02 is subjected to a gelation treatment, converting the contained liquid hydrogel membrane layer from a liquid state to a gel state, forming a hydrogel base membrane 1, and producing a composite membrane. This composite membrane is the composite membrane described above and will not be described again here.

[0067] In some embodiments, the gelation process of the hydrogel composite membrane can be achieved by cooling. By lowering the temperature of the hydrogel composite membrane, the liquid hydrogel layer in the hydrogel composite membrane is gelled, forming a gelled hydrogel base membrane 1, and thus the composite membrane is manufactured. For example, by lowering the temperature of the hydrogel composite membrane to room temperature, the liquid hydrogel solution layer can be gelled, forming a gelled hydrogel base membrane 1. The cooling process of the gelation treatment may be carried out by a cooling device or by natural cooling. In this way, the use of additional cooling devices is not required, reducing the energy consumption of the gelation treatment and further reducing the production cost of the composite membrane manufacturing method according to the embodiments of this invention.

[0068] In some embodiments, the gelation temperature may be 0 to 35°C. By controlling the gelation temperature within this range, the liquid hydrogel solution in the hydrogel composite membrane is rapidly gelled, forming the hydrogel base membrane 1, manufacturing the composite membrane, and increasing the efficiency of composite membrane production.

[0069] In a third aspect, the present invention provides applications of the composite film in biosensors, electronic skin, and flexible electronic devices.

[0070] Because the above-mentioned composite membrane possesses excellent properties such as good breathability, resistance to drying, mechanical properties, and skin compatibility, it has broad potential applications in biosensors, electronic skin, and skin electrodes.

[0071] In some embodiments, the flexible electronic device may be an electronic device for monitoring physiological electrical signals, such as a skin electrode.

[0072] In a fourth aspect, the present invention provides a biosensor comprising the above-described composite membrane.

[0073] The biosensor according to the embodiment of the present invention further comprises an electronic system. The composite membrane according to the embodiment of the present invention can effectively connect the electronic system to biological tissue, particularly skin tissue. Because the composite membrane has good breathability, anti-drying properties, tensile strength, flexibility, adhesion, and skin compatibility, the biosensor according to the embodiment of the present invention can establish a good, effective, and stable connection with biological tissue. Due to the good performance of each surface of the composite membrane, the biosensor has good comfort during use and can avoid problems of skin redness and swelling with long-term use.

[0074] The following describes the composite film, its manufacturing method, applications, sensors, etc., according to the embodiments of this invention, using several specific examples.

[0075] Example 1 This embodiment provides a composite film comprising a hydrogel-based film and reinforcing ribs placed within the hydrogel-based film. The reinforcing rib layer contains intertwined fibers. The thickness of the reinforcing rib layer is 0.2 μm, the fiber material is TPU, and the fiber diameter is 900 nm. The components of the hydrogel-based film are shown in Table 1 below.

[0076] As shown in Figure 3, the manufacturing process of the composite film is as follows.

[0077] Step S1, Fabrication of reinforcing ribs. TPU (Manufacturer: BASF, Model: 1815A) was dissolved in a 1:1 mass ratio mixture of N,N-dimethylformamide (DMF) and tetrahydrofuran (THF) to prepare an electrospinning solution with a TPU concentration of 13 wt%. The electrospinning solution was placed in a 5 mL syringe (27 G needle) and electrospinned under 11 kV conditions, resulting in a density of 0.27 mg / cm³. 2 A nanomesh was manufactured and used as a reinforcing rib. The fiber diameter of the reinforcing rib is 900 nm.

[0078] Step S2: Preparation of conductive hydrogel solution Appropriate amounts of gelatin, glycerin, sodium tetraborate, and sodium sulfate were taken and dissolved in water to prepare a hydrogel solution. The hydrogel solution was allowed to stand at 75°C for 2 hours, and air bubbles were removed. The mass fractions of each component in the hydrogel solution are shown in Table 1.

[0079] Step S3, Composite film fabrication. The reinforcing ribs are fixed with a support frame, transferred, immersed in the hydrogel solution, removed, and coated by immersion to form a liquid hydrogel film layer. The reinforcing ribs form a reinforcing rib layer and are embedded within the hydrogel film layer. The hydrogel film layer and the reinforcing rib layer constitute a liquid hydrogel composite film. The hydrogel composite film is left at room temperature to cool for 2 minutes, causing the liquid hydrogel in the liquid hydrogel film layer to gel, forming a hydrogel base film and fabricating the composite film.

[0080] Examples 2 to 16 Examples 2 to 16 each provide a composite film. The manufacturing methods for the composite films in Examples 2 to 12 are almost the same as in Example 1, with the differences being the thickness and density of the reinforcing ribs, the material and diameter of the fibers, and the components and content of the hydrogel solution, which are specifically shown in Table 1.

[0081] [Table 1]

[0082] Comparative Example 1 This comparative example provides a hydrogel-based film, the composition of which is the same as that of the hydrogel-based film in the composite film according to Example 1. The manufacturing process of the hydrogel-based film according to this comparative example is as follows.

[0083] A support frame measuring 2 cm in length and width and 0.125 mm in thickness was immersed in the hydrogel solution of Example 1, removed, and a liquid hydrogel film layer was formed on the frame. The hydrogel film layer was then cooled at room temperature for 2 minutes to gel, thereby producing the hydrogel base film of Comparative Example 1.

[0084] Performance testing The nanomesh produced in Example 3 was observed with a scanning electron microscope, and the composite film prepared in Example 1 was taken, freeze-dried, and then observed with a scanning electron microscope. The results are shown in Figures 4 and 5.

[0085] As shown in Figure 4, the reinforcing rib layer in Example 3 is a mesh-like structure formed by intertwined fibers, with a fiber diameter of approximately 900 nm. As shown in Figure 5, in the composite membrane of Example 1, the fibers in the reinforcing rib layer intertwine to form a nanomesh, and the hydrogel-based membrane covers the nanomesh. The hydrogel-based membrane has a porous structure, and these porous structures give the hydrogel good permeability, and the composite membrane also has good permeability.

[0086] The composite film produced in Example 1 was taken, cut to a size of 4 cm x 4 cm, and attached to the skin to examine its skin compatibility, which is shown in Figure 6. The composite film produced in this embodiment adhered closely to the skin surface, naturally folded in accordance with changes in the skin under tension and extrusion conditions, and did not exhibit significant wrinkles or shedding, demonstrating good skin compatibility.

[0087] The composite films produced by Examples 1 to 16 and the hydrogel-based film produced by Comparative Example 1 will be tested for thickness, tensile strength, drying resistance, air permeability, tackiness per unit area, and conductivity. The tensile strength of the reinforcing rib produced by Example 1 will also be measured under the same conditions.

[0088] The thickness is measured using a Bruker probe profiler (Dektak XT) and a scanning electron microscope.

[0089] Tensile performance is measured using a universal tensile testing machine (Mark-10). The tensile performance is measured using a Mark-10 universal tensile testing machine equipped with a 10N pressure measuring element. The sample is mounted vertically in the fixture of the tensile testing machine, and both sides of the frame are cut with a sharp cutter. The sample is pulled at a tensile speed of 10 mm / min, and the stress and strain during the pulling process are recorded.

[0090] The test method for drying resistance is as follows: The composite membrane is taken, its initial weight is measured, the weighed hydrogel is left at 25°C and 45-70% RH for a certain period (e.g., 7 days, 10 days, etc.), its weight is measured again, and the anti-drying properties of the composite membrane are calculated using formula (1).

[0091]

number

[0092] The test method for breathability is as follows: A glass bottle containing 20g of water is covered with the composite membrane to be measured, its weight is measured, the glass bottle is placed at 25°C and 30%RH, its weight is measured daily, the weight of the water lost from the glass bottle is calculated, and the permeability of the composite membrane is calculated using formula (2).

[0093]

number

[0094] Adhesion performance is measured by a 90° peel test. The sample is attached to the surface of artificial skin, with an initial adhesion area of ​​10 × 10 mm. 2 The adhesive strength at which the ultrathin hydrogel and artificial skin completely separate is recorded using a Mark-10 universal testing machine at a vertical tensile speed of 20 mm / s. The adhesive performance is calculated using the following formula (3).

[0095]

number

[0096] The thickness, tensile performance, drying resistance, air permeability, and adhesive performance of the composite films from Examples 1 to 12, and the hydrogel-based film from Comparative Example 1, as well as the tensile performance test results of the reinforcing ribs from Example 1, are shown in Table 2 and Figures 7 to 12.

[0097] [Table 2]

[0098] As shown in Table 2 and Figures 7-12, the composite film according to the embodiment of this application has an ultrathin structure. The thickness of the composite film according to Example 1 can be as low as 10 μm and can be adjusted according to actual demand. When the thickness of the composite film is as low as 10 μm, the composite film still has good tensile performance, which demonstrates that the composite film according to the embodiment of this application achieves a balance between thickness and mechanical properties.

[0099] Compared to the hydrogel-based film of Comparative Example 1, the composite film of Example 1 has the same thickness and the same hydrogel components. The only difference is that the composite film of Example 1 has a reinforcing rib layer on the hydrogel-based film. As shown in Figure 9, the tensile performance of the composite film of Example 1 is 606%, which is far higher than the tensile performance of the hydrogel-based film of Comparative Example 1, which is 364%. Furthermore, the tensile performance of the composite film of Example 1 is also higher than the tensile performance of the nanomesh of Example 1. This indicates that the tensile performance of the composite film of Example 1 is improved not only by the action of the reinforcing rib layer, but also by the interaction between the hydrogel-based film and the reinforcing rib layer.

[0100] Referring to Table 2 and Figure 10, the proportion of each component in the hydrogel-based membrane according to the present embodiment results in the composite membrane having good anti-drying properties, effectively retaining moisture in the hydrogel-based membrane over a long period, and providing favorable conditions for the application of the composite membrane in long-term physiological health detection.

[0101] The composite film according to the present embodiment has good breathability. Furthermore, referring to Figure 11, there was no significant difference in the composite film test results according to Example 1, for example, the test results without coverage, but there was a significant difference compared to the control group with PDMS coverage, indicating that the composite film according to the present embodiment has good breathability.

[0102] The composite films produced in Examples 1 to 16 exhibit good adhesive properties. Referring to Table 2 and Figure 12, there is no significant difference between the adhesive performance per unit area of ​​the composite film produced in Example 1 and the hydrogel-based film produced in Comparative Example 1.

[0103] Due to the excellent skin compatibility, mechanical properties, anti-drying properties, breathability, and adhesive properties of the composite film according to the embodiment of this invention, the composite film according to this invention can maintain good and stable contact with the skin for a long period of time and can be applied to electrophysiological signal monitoring over the long term.

[0104] Physiological monitoring performance test The composite membrane from Example 1 described above was used as a biosensor, and signal monitoring of electrocardiograms, electromyograms, electroencephalograms, electrooculograms, and evoked potentials was performed under the same conditions as with a commercial Ag / AgCl hydrogel electrode from NIHON KOHDEN. The results are shown in Figures 13 to 17.

[0105] One of the prerequisites for achieving high-quality long-term health monitoring is establishing a stable, low-impedance interface between the electrode and the skin. Stable, low skin contact impedance enables a higher signal-to-noise ratio and more accurate recording of biosignals. As shown in Figure 13A, the skin contact impedance of the composite membrane according to this embodiment is lower than that of commercial gel electrodes. Under conditions of 100 Hz, the skin contact impedance of the composite membrane according to this embodiment is 31.3 kΩ, while the skin contact impedance of commercial gel electrodes is 57.5 kΩ. Furthermore, the skin contact impedance curve after 24 hours of continuous wear of the composite membrane closely matches the initial skin contact impedance curve. This indicates that the composite membrane according to this embodiment can provide a long-term stable connection. Because the composite membrane according to this embodiment has low skin contact impedance, high compatibility, mechanical robustness, and water retention, it offers the advantages of high comfort, good connection stability, and low electrode impedance in applications for physiological signal monitoring, enabling high-quality long-term health monitoring.

[0106] Furthermore, as shown in Figure 13, in the case of electrocardiogram monitoring, two composite membranes according to Example 1 are placed on the chest of the subject and connected to a portable sensor equipped with a Bluetooth® element to capture the electrocardiogram signal in real time and perform long-term monitoring. In addition, in the initial stage of electrocardiogram signal monitoring of the composite membrane according to Example 1, electrocardiogram signal monitoring is performed under the same conditions using a commercial Ag / AgCl electrode.

[0107] The electrocardiogram signals monitored by the composite membrane according to the present invention have similar waveforms to those of commercial Ag / AgCl electrodes (signal-to-noise ratio: 29.7±1.0dB), and the signal-to-noise ratio of the composite membrane according to the present invention is higher at 32.8±1.6dB. Due to its long-term water retention properties, the composite membrane according to the present invention exhibits high-quality and high-fidelity electrocardiogram signals for up to 21 days (the signal-to-noise ratio on day 21 is 29.8±2.0dB, close to the signal-to-noise ratio at the initial measurement), and has no negative effects on the skin.

[0108] As shown in Figures 14 to 17, when the embodiment of this invention is applied to the monitoring of physiological signals such as electromyography, electrooculography, electroencephalography, and somato-evoked potentials, the composite membrane according to the embodiment of this invention exhibits a monitoring effect close to or better than that of commercial gels at the initial stage of monitoring. Furthermore, the monitoring effect of the composite membrane according to the embodiment of this invention after 24 hours of continuous monitoring does not differ significantly from the monitoring effect at the initial stage. The composite membrane according to the embodiment of this invention has been successfully applied to the long-term monitoring of physiological signals such as electrocardiography, electromyography, electrooculography, electroencephalography, and somato-evoked potentials, providing a novel method for skin electronic devices and representing an important step toward personalized medicine.

[0109] The above embodiments illustrate several embodiments of the present application and are described in a specific and detailed manner, but are not to be construed as limiting the scope of the patent of the present application. Furthermore, several modifications and improvements are possible for those skilled in the art without departing from the spirit of the present application, and these are also included within the scope of protection. Accordingly, the scope of protection of the present application is as defined in the attached claims.

Claims

1. A composite membrane comprising a hydrogel-based membrane, wherein a reinforcing rib layer is embedded within the hydrogel-based membrane, and the reinforcing rib layer is positioned along the extending direction of the hydrogel-based membrane. The reinforcing rib layer contains some fibers, and the material of the fibers contains an elastic polymer. A composite film characterized in that the thickness of the reinforcing rib layer is 0.1 to 4.0 μm.

2. The diameter of a single fiber is 180 to 1600 nm, and / or The aforementioned fibers intertwine to form a network structure, and / or, The density of the reinforcing rib layer is 0.1 to 3.6 mg / cm³. 2 and / or, The composite film according to claim 1, characterized in that the elastic polymer comprises at least one of TPU, SBS, SEBS, PET, PLGA, PI, and PVDF.

3. If the mass of the hydrogel-based membrane is taken as 100%, then the hydrogel-based membrane is composed of water and, A substrate with a mass percentage content of 2-15%, Water-retaining agents with a mass percentage content of 0-30%, Crosslinking agents with a mass percentage content of 0-5%, Conductive agents with a mass percentage content of 0-3%, A composite film according to claim 1 or 2, characterized by containing the following component.

4. The substrate comprises at least one of gelatin, carrageenan, locust bean gum, and / or guar gum. The water-retaining agent comprises at least one of an alcohol compound, a highly hydrated salt, and an anionic surfactant, and / or The crosslinking agent comprises at least one of sodium tetraborate, sodium citrate, and tannic acid, and / or The composite film according to claim 3, characterized in that the conductive agent includes an ionic compound.

5. The alcohol compounds include at least one of glycerin, ethylene glycol, 1,2-propylene glycol, and 1,3-propylene glycol, and / or The aforementioned highly hydrated salt contains lithium chloride and / or, The aforementioned anionic surfactant contains and / or, The composite membrane according to claim 4, characterized in that the ionic compound comprises at least one of sodium sulfate, sodium chloride, sodium nitrate, potassium sulfate, sodium acetate, potassium chloride, and potassium nitrate.

6. The thickness of the composite film is 7 to 200 μm, and / or The tensile strength of the composite film is 450% to 800%, and / or The permeability of the composite membrane is 0.1 to 3.0 kg m -2 d -1 and / or, After storing the composite membrane for 1 to 21 days, the water retention rate is 90% or more, and / or The adhesive strength per unit area of ​​the composite film is 10 to 220 μJ / cm². 2 A composite film according to any one of claims 1, 2, 4, or 5, characterized in that it is such.

7. A step of providing a hydrogel solution and reinforcing ribs, The process involves forming a film on the hydrogel solution and the reinforcing ribs to obtain a liquid hydrogel composite film, and the reinforcing ribs forming a reinforcing rib layer in the hydrogel composite film. The process includes a step of gelling the hydrogel composite membrane to produce the composite membrane, The reinforcing rib layer contains some fibers, and the material of the fibers contains an elastic polymer. A method for manufacturing a composite film, characterized in that the thickness of the reinforcing rib layer is 0.1 to 4.0 μm.

8. The reinforcing ribs are manufactured by an electrospinning method and / or The temperature of the hydrogel solution is 50 to 80°C, and / or The temperature of the gelation treatment is 0 to 35°C. The manufacturing method according to claim 7, characterized in that the gelation time is 2 to 3 minutes.

9. Applications of a composite film according to any one of claims 1 to 6 or a composite film manufactured by a method for manufacturing a composite film according to claim 7 or 8, in biosensors, electronic skin, and flexible electronic devices.

10. A biosensor characterized by comprising a composite membrane according to any one of claims 1 to 6, or a composite membrane manufactured by a method for manufacturing a composite membrane according to claim 7 or 8.

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