Electrochemical device and method for producing same

Abstract

The present disclosure provides a highly sensitive wearable electrochemical device that can be attached to a complex shaped region of a living body or the like. The present disclosure relates to an electrochemical device comprising: a fiber sheet having flexibility and conductivity and having a non-woven fabric structure; and a hydrogel, wherein the hydrogel is retained in a gap of the non-woven fabric structure of the fiber sheet.

Description

Electrochemical devices and methods for manufacturing the same

[0001] The present invention relates to an electrochemical device and a method for manufacturing the same.

[0002] In recent years, electronic devices have been used in automobiles, social infrastructure, and health monitoring, making a significant contribution to improving the quality of life. In particular, electronic devices that are attached to the body to chemically monitor substances that indicate health status will be important equipment for extending healthy life expectancy in the future.

[0003] Anke Weidenkaff et al., Nature Reviews Materials 6, pages 462.463 (2021)Xiang, H. et al., npj Flex Electron 6, 15 (2022)Wenhui Li et al., Adv. Mater. 32, 2001591 (2020)Jo, H., Ban, C., Exp Mol Med 48, e230 (2016)

[0004] Therefore, there is a need for a wearable device that can be attached to complex-shaped parts of living organisms and other structures, and that is capable of highly sensitive electrochemical measurements.

[0005] The gist of the present invention is as follows: (1) An electrochemical device comprising a fiber sheet having flexibility and conductivity and a nonwoven fabric structure, and a hydrogel, wherein the hydrogel is held in the gaps of the nonwoven fabric structure of the fiber sheet. (2) The electrochemical device according to (1) above, wherein the hydrogel has a molecular recognition substance including an electron transfer mediator, an enzyme, an aptamer, an antibody, or a combination thereof. (3) The electrochemical device according to (1) or (2) above, wherein the fiber sheet has a conductive film on the surface of the fibers constituting the fiber sheet. (4) The electrochemical device according to (3) above, wherein the conductive film is a noble metal film. (5) The electrochemical device according to (3) or (4) above, wherein the conductive film is a metal plating film. (6) The electrochemical device according to any one of (3) to (5) above, wherein the conductive film is an Au plating film or a Pt plating film. (7) The electrochemical device according to any one of (1) to (6) above, wherein the fibers constituting the fiber sheet have an average diameter of 50 nm or more and less than 1000 nm. (8) The electrochemical device according to any one of (3) to (6) above, wherein the conductive film has an average thickness of 10 to 300 nm. (9) The electrochemical device according to any one of (1) to (8) above, wherein the fibers constituting the fiber sheet are polylactic acid (PLA), polyester, polyamide, polyurethane, or a combination thereof. (10) The electrochemical device according to any one of (1) to (9) above, wherein the hydrogel is a zwitterionic group-containing polymer hydrogel. (11) The electrochemical device according to any one of (1) to (10) above, wherein the hydrogel is a hydrogel formed from a copolymer containing monomer unit A having a zwitterionic group in its side chain and monomer unit B having an N-succinimide ester group in its side chain as repeating units. (12) An electrochemical device according to any one of (1) to (11) above, which is an electrochemical sensor, a biosensor, a transducer, a biofuel cell, a drug delivery carrier, or an electrode thereof.(13) A method for producing an electrochemical device, comprising: creating a flexible fiber sheet having a nonwoven fabric structure by electrospinning; forming a metal plating film on the surface of the fibers contained in the fiber sheet by electroless plating to make the fiber sheet conductive; preparing a hydrogel; and combining the conductive fiber sheet and the hydrogel to obtain an electrochemical device. (14) A method for producing an electrochemical device according to (13), further comprising combining the hydrogel with a molecular recognition substance including an electron transfer mediator, an enzyme, an aptamer, an antibody, or a combination thereof. (15) A method for producing an electrochemical device according to (13) or (14), wherein combining the conductive fiber sheet and the hydrogel includes physically holding the hydrogel in the conductive fiber sheet. (16) A method for producing an electrochemical device according to (13) or (14), wherein combining the conductive fiber sheet and the hydrogel includes chemically bonding the conductive fiber sheet and the hydrogel.

[0006] According to the present invention, it is possible to provide a wearable, highly sensitive electrochemical device that can be attached to complexly shaped parts of living organisms and the like.

[0007] Figure 1 is a photograph of an example of a PLA fiber sheet formed on aluminum foil using the electrospinning method. Figure 2 is a scanning electron microscope (SEM) image of the PLA fiber sheet shown in Figure 1. Figure 3 is an SEM image of an example of an Au / PLA fiber sheet in which an Au film was formed on the surface of the PLA fibers constituting the PLA fiber sheet by electroless plating. Figure 4 shows the qualitative analysis results by SEM-EDX of an Au / PLA fiber sheet with an Au film formed on the surface of the PLA fibers by electroless plating and a PLA fiber sheet without plating. Figure 5 is a photograph of the Au / PLA fiber sheet prepared in Example 1 being held with tweezers. Figure 6 shows the stress-strain curves of the Au / PLA fiber sheet prepared in Example 1 and a PLA fiber sheet without plating. Figure 7 shows the Au / PLA fiber sheet prepared as an electrode and 10 mM Fe[CN] as an electrolyte. ６ ] ３－／４－ Figure 8 shows the cyclic voltammetry (CV) results for 255 cycles performed using [tool name]. Figure 8 shows the CV results for the Au / PLA fiber sheet prepared as an electrode in Example 1 and the Au-plated flat PLA prepared in Comparative Example 1. Figure 9 shows photographs of the appearance of the hydrogel membrane with the enzyme physically bound and the hydrogel membrane with the enzyme chemically bound, held with tweezers. Figure 10 shows a photograph of the appearance of the device prepared by embedding an enzyme-encapsulated hydrogel (Gel / AFc / GOD) with the enzyme physically immobilized in the gap of the three-dimensional nonwoven fabric structure at one end of a strip-shaped Au / PLA fiber sheet with the central part covered with polyimide tape. Figure 11 shows the 0.5M H of the PLA fiber sheet prepared using the electrospinning method in Example 1 with electroless Au plating and the flat PLA with electroless Au plating in Comparative Example 1. ２ SO ４This graph compares the CV characteristics in the following locations. Figure 12 shows the CV curve of the glucose response observed 3 days after immersion of the electrochemical device prepared in Example 1 in a 5 mM glucose solution. Figure 13 shows the CV curve of the glucose response observed 2 days after immersion of the electrochemical device prepared in Comparative Example 1 in a 5 mM glucose solution. Figure 14 shows photographs of the electrochemical device prepared in Example 1 when bent to 0, 45, and 90 degrees in a 5 mM glucose solution. Figure 15 shows the CV curve measured while bending the electrochemical device at the above angles in a 5 mM glucose solution. Figure 16 shows SEM images of fibers prepared using (a) 6.7 mass%, (b) 8 mass%, and (c) 10 mass% PLA solutions.

[0008] This disclosure relates to an electrochemical device comprising a fiber sheet having a nonwoven fabric structure that is flexible and conductive, and a hydrogel, wherein the hydrogel is held in the gaps of the nonwoven fabric structure of the fiber sheet.

[0009] The inventors have discovered a high-performance and flexible electrochemical device (hereinafter also referred to as "this device") by using a flexible fiber sheet having a nonwoven fabric structure as a base material, and by compounding the fiber sheet, which has conductivity extending to the interior of the three-dimensional nonwoven fabric structure and also functions as an electrode, with a hydrogel.

[0010] Using fiber sheets with a nonwoven fabric structure as electrodes improves the performance of electrochemical devices because they have a large electrode surface area. Furthermore, because nonwoven fiber sheets are flexible, they have high biocompatibility and can be attached to any part of the body.

[0011] Since hydrogels can contain molecular recognition materials including electron transfer mediators, enzymes, aptamers, antibodies, or combinations thereof, this device can be a variety of electrochemical electronic devices.

[0012] This device, which includes a hydrogel capable of immobilizing molecular recognition substances, possesses biocompatibility that nonspecifically suppresses the adhesion of biomolecules such as proteins. It not only exhibits excellent biocompatibility but also contributes to improved performance as an electrochemical sensor, such as high selectivity and extended lifespan. If the hydrogel contains enzymes, this device can function as an electrochemical sensor detecting glucose, lactic acid, alcohol, etc., depending on the type of enzyme.

[0013] This device possesses excellent conductivity, extending even to the interior of the nonwoven fiber sheet structure, making it a highly sensitive and high-performance electronic device. Because the device uses a fiber sheet with a nonwoven structure as its base material and is flexible, it can be wearable and function as a biosensor for biological measurements. For example, this device can be used as a wearable biosensor for continuous monitoring of living organisms.

[0014] This device can be suitably used, for example, as an electrochemical sensor, biosensor, transducer, biofuel cell, drug delivery carrier, or electrode thereof. Depending on the molecular recognition substance held in the hydrogel, this device can be used as a highly sensitive biosensor specific to the target of measurement, and the biosensor can be a glucose sensor, etc.

[0015] Flexibility refers to both flexibility and stretchability. Flexibility means ease of bending; the fiber sheet will not break even when bent at an angle of 90 degrees or more, and will substantially maintain its properties before and after bending. Stretchability refers to ease of stretching and contracting, which can be measured by stress-strain testing. In the measurement of the stress-strain curve, the strain is preferably 100% or more, more preferably 150% or more, and even more preferably 200% or more. The stress-strain curve can be measured using a stress-strain testing machine.

[0016] The raw materials for the fibers that make up the fiber sheet are not particularly limited as long as they can form a fiber sheet with a nonwoven fabric structure by forming a film using the electrospinning method, and can be selected according to the application.

[0017] The fibers are preferably composed of polylactic acid (PLA), polyester, polyamide, polyurethane, or a combination thereof. The fibers may also be composed of biopolyethylene (bioPE), polystyrene, polyvinyl alcohol (PVA), chitosan, polycaprolactone, polybutylene adibate terephthalate (PBAT), microbially produced polyester (PHA), polybutylene succinate (PBS), polybutylene succinate adipate (PBSA), or a combination thereof.

[0018] PLA and bio-PE are plastics made from biological resources (biomass), and PLA is biodegradable. PLA can be easily synthesized from corn, cassava, sugarcane, starch, etc., and is thermoplastic. PVA is a petroleum-derived biodegradable plastic. Chitosan is a natural polysaccharide derived from chitin found in the exoskeletons of insects, shrimp, crabs, etc., and is a plant- and animal-derived biodegradable plastic. Polycaprolactone and polybutylene adivate terephthalate (PBAT) are petroleum-derived biodegradable plastics. Microbial-produced polyester (PHA) is a biomass plastic that is biosynthesized within microorganisms using sugars and vegetable oils as raw materials, and is also a biodegradable plastic that is decomposed in various environments such as mountains, rivers, and seas by decomposing microorganisms present in the natural environment. Polybutylene succinate (PBS) and polybutylene succinate adipate (PBSA) are biodegradable plastics that are naturally broken down into water and carbon dioxide by microorganisms in the soil.

[0019] The fiber sheet functions as a substrate in this device and, by having a metal film on the surface of the fibers even within the nonwoven fabric structure, can also function as a highly conductive electrode. Furthermore, because the fiber sheet substrate is flexible, the electrodes and the entire device are flexible, making it wearable. For example, while PLA fibers have low flexibility if their diameter is too large, fiberizing PLA allows for the creation of a fiber sheet with good flexibility.

[0020] The raw materials for the fibers can be anything that can be used in living organisms, preferably with biocompatibility, and may even be for medical use.

[0021] Figure 1 shows an external photograph of an example of a PLA fiber sheet formed on aluminum foil using the electrospinning method. Figure 2 shows a scanning electron microscope (SEM) image of the PLA fiber sheet shown in Figure 1. As illustrated in Figure 2, the PLA fiber sheet has a nonwoven fabric structure. Because the fiber sheet has a nonwoven fabric structure, hydrogel can be inserted into and held in the gaps (voids) of the nonwoven fabric structure.

[0022] The average diameter of the fibers constituting the fiber sheet is preferably 50 nm or more, more preferably 100 nm or more, even more preferably 200 nm or more, even more preferably 300 nm or more, and even more preferably 400 nm or more, with an upper limit of less than 3000 nm or less than 2000 nm, preferably less than 1000 nm, more preferably 900 nm or less, even more preferably 800 nm or less, even more preferably 700 nm or less, and even more preferably 600 nm or less. By having the above preferred diameters, the fibers constituting the fiber sheet can have a nonwoven fabric structure with better flexibility and voids suitable for the substrate and electrodes of this device. The average diameter of the fibers can be measured based on SEM images.

[0023] The thickness of the fiber sheet can be adjusted by changing the electrospinning deposition time, and preferably has an average thickness of 10 nm to 100 μm. Having the above preferred thickness allows the fiber sheet to have good flexibility. The fiber sheet may be a single sheet or a laminate of multiple sheets. When creating a fiber sheet by stacking multiple fiber sheets, a wet press can be used, in which drying and pressing are performed simultaneously while the sheet is still containing liquid.

[0024] The fiber sheet only needs to have voids that allow for the insertion of the hydrogel. The porosity can be adjusted by controlling the diameter of the fibers that make up the fiber sheet. By having voids that allow for the insertion of the hydrogel, the fiber sheet can hold molecular recognition material while maintaining flexibility.

[0025] The fibers constituting the fiber sheet can each have a conductive film on its surface. Since all the fibers constituting the sheet have a conductive film and are conductive, the fiber sheet can function as an excellent electrode for an electrochemical device. In this device, the fiber sheet holds hydrogel in the gaps of the nonwoven fabric structure, and not only the fibers on the surface of the three-dimensional nonwoven fabric structure but also the internal fibers constituting the sheet have a conductive film. Therefore, it has a large conductive surface area and exhibits superior conductivity compared to cases where the conductive film is only on the surface of the substrate, and can function as an electrode for an electrochemical device with very high sensitivity (output), such as an electrode for a biosensor.

[0026] The sensitivity of the fiber sheet as an electrode can be compared, for example, by the peak currents Ip a (oxidation current) and Ip c (reduction current) in the cyclic voltammetry (CV) of a redox pair substance such as ferrocyanide ion. In CV, the fiber sheet composed of fibers having a conductive film on the surface has a sensitivity preferably 3 times or more, more preferably 4 times or more, still more preferably 5 times or more, and even more preferably 10 times or more than that of a flat polymer sheet of the same thickness having a conductive film only on the surface.

[0027] The conductivity of the fiber sheet composed of fibers having a conductive film on the surface can be, for example, 10 ５ S / m. When the fiber sheet has the preferred conductivity, it can function better as an electrode of an electrochemical device. The conductivity can be measured using the four-probe method.

[0028] The conductive film is composed of a conductive metal, preferably a noble metal film, more preferably an Au film, a Pt film, or an Ag film, still more preferably an Au film or a Pt film, and even more preferably an Au film. Au films and Pt films are preferred in that they have high conductivity and excellent biocompatibility. The Au film can perform better functional group substitution by surface modification with Au-thiol bonds in order to immobilize a gel on the surface.

[0029] The conductive film is preferably a metal plating film, more preferably an electroless metal plating film. A metal film such as an Au plating film or a Pt plating film can be formed on the surface of the insulating fibers constituting the fiber sheet by electroless plating, and the metal plating film can be formed not only on the surface fibers but also on the internal fibers of the non-woven fabric structure.

[0030] The average thickness of the conductive film on the fiber surface is preferably 10 nm or more, 50 nm or more, or 100 nm or more as the lower limit value, and preferably 300 nm or less, 250 nm or less, or 200 nm or less as the upper limit value. By having the conductive film on the fiber surface with the preferred thickness, conductivity, flexibility, and voids in the non-woven structure can be better. The average thickness of the conductive film may be calculated from the difference in the average diameter of the fibers measured from the SEM observation images before and after the formation of the conductive film.

[0031] Fig. 3 shows a SEM image of an example of an Au / PLA fiber sheet in which an Au film is formed on the surface of PLA fibers constituting a PLA fiber sheet by electroless plating. Au plating is applied not only to the surface but also to the inside of the non-woven structure in which the fibers are three-dimensionally stacked. Au particles can be seen on the surface of the Au film. Electroless plating can form a conductive film with a substantially uniform thickness up to the inside of the three-dimensional structure. The type of metal of the metal film can be measured by SEM-EDX (energy dispersive X-ray spectroscopy).

[0032] Since the Au / PLA fiber sheet has an Au film with a substantially uniform thickness up to the inside of the three-dimensional structure, its sensitivity as an electrode of an electrochemical device, particularly as an electrode of a sensor, is extremely excellent compared to the case where only the surface has an Au film. In CV where a measurement target substance for evaluating an electrochemical device is dissolved in a solution and the current value is measured, the Au / PLA fiber sheet has a sensitivity preferably 3 times or more, more preferably 4 times or more, and even more preferably 5 times or more compared to the same thickness of PLA having only an Au film on the surface.

[0033] A hydrogel is a gel composed of polymers having zwitterionic functional groups, and can be a copolymer gel. A hydrogel is an aggregate consisting of nano to micrometer-sized particulate matter. Such hydrogels easily penetrate the gaps in the nonwoven fabric structure of a fiber sheet. Because hydrogels contain water, they are easily deformable, and can be pressed into the gaps in the nonwoven fabric structure of a fiber sheet. The water contained in the hydrogel may be removed during the pressing process. The diameter of the gel particles can be measured by dynamic light scattering (DLS) or microscopic observation. The diameter of the gel particles constituting the hydrogel can be adjusted by the molecular weight of the polymer or, in the case of a copolymer, the monomer ratio. The method for adjusting the molecular weight of the polymer is not particularly limited and can be done, for example, by increasing or decreasing the concentration of the radical initiator, changing the reaction time, changing the monomer ratio, or, in reversible addition-cleavage chain transfer polymerization (RAFT polymerization), by changing the monomer concentration and chain transfer agent concentration.

[0034] A hydrogel can be used to immobilize a molecular recognition substance by physically or chemically bonding it, preferably covalently. The hydrogel is preferably a polymer hydrogel containing zwitterionic groups. A zwitterionic group has a structure with both positive and negative charges, and is also called an amphoteric group. The presence of zwitterionic groups imparts hydrophilicity to the copolymer, allowing for better maintenance of the molecular recognition substance after immobilization. The hydrogel can be biocompatible, making it a safer device for biomedical measurements.

[0035] The hydrogel is preferably formed from a copolymer containing monomer units A having zwitterionic groups in their side chains and monomer units B having N-succinimide ester groups in their side chains as repeating units. Monomer units A and B may be randomly bonded, or they may have a predetermined regularity or periodicity, for example, they may be alternating polymers, periodic polymers, block copolymers, or graft polymers. The copolymer may contain monomer units other than monomer units A and B. The copolymer may also contain monomer units having hydrophobic groups in their side chains, and if necessary, the amount of water contained in the hydrogel may be reduced to further improve its strength. In this application, the term hydrogel includes states ranging from a solid state where fluidity has been lost to a state where fluidity is observed.

[0036] Preferably, examples of zwitterionic groups include (a) a phosphorylcholine group (phosphobetaine group), (b) a sulfobetaine group, or (c) a carboxybetaine group. The phosphorylcholine group (PC group) is a polar group that has a structure similar to the polar group of phospholipids (phosphatidylcholine), which are the main components of biological membranes.

[0037] The N-succinimide ester group contained in monomer unit B in the copolymer is a highly reactive active ester, allowing molecular recognition substances to be immobilized on the hydrogel. The molecular recognition substance is preferably immobilized on the hydrogel by covalent bonds. For example, it can react with amino groups in proteins to form covalent bonds (amide bonds), allowing enzymes to be immobilized in the hydrogel. Similarly, electron transfer mediator compounds having amino groups can also be immobilized by forming covalent bonds. For example, a copolymer can be obtained in which a ferrocenyl group is included in the side chain of monomer unit B by reacting the amino group of aminoferrocene (AFc) as an electron transfer mediator with the N-succinimide ester group. Aptamers and antibodies can also have amino groups and can be immobilized on the hydrogel, preferably by covalent bonds.

[0038] The polymerization sites in the monomer units that form the main chain (skeleton) structure of the copolymer are not particularly limited, as long as they can polymerize with each other to form a polymer. For example, vinyl monomer residues, acetylene monomer residues, ester monomer residues, amide monomer residues, ether monomer residues, urethane monomer residues, etc. are preferred, and vinyl monomer residues are more preferred. The vinyl monomer residues are not limited, but for example, methacryloxy groups, methacrylamide groups, acrylicoxy groups, acrylamide groups, styryloxy groups, styrylamide groups, etc., in a state where the vinyl portion has undergone addition polymerization can be used, with methacryloxy groups being preferred. The polymerization sites may be the same for each monomer unit, or they may be independently different, but it is preferable that they are all vinyl monomer residues, particularly methacryloxy groups. Therefore, in the preferred embodiment, the main chain structure of the copolymer has a structure in which vinyl groups are polymerized, and more preferably has an acrylic polymer structure.

[0039] The monomer unit A is preferably of the following formula (I): It has a structure represented by the formula, where R １ R represents a linear or branched alkyl group having 1 to 5 carbon atoms, preferably a linear alkyl group having 1 to 5 carbon atoms, and more preferably a methyl group. ２ R represents a linear or branched alkylene having 1 to 20 carbon atoms, preferably a linear alkylene having 1 to 5 carbon atoms, and more preferably a methylene group. ５ represents a directly bonded alkylene group or a linear or branched alkylene group having 1 to 20 carbon atoms.

[0040] Specific examples of the monomer unit A are not particularly limited. For example, structural units derived from 2-methacryloyloxyethyl phosphorylcholine, 2-acryloyloxyethyl phosphorylcholine, N-(2-methacrylamide)ethyl phosphorylcholine, 4-methacryloyloxybutyl phosphorylcholine, 6-methacryloyloxyhexyl phosphorylcholine, 10-methacryloyloxydecyl phosphorylcholine, ω-methacryloyldioxyethylene phosphorylcholine, 4-styryloxybutyl phosphorylcholine, etc. may be mentioned, and a structural unit derived from 2-methacryloyloxyethyl phosphorylcholine is preferable. The above examples are those having a phosphorylcholine group as an amphoteric ion group, but monomer units in which a portion corresponding to the phosphorylcholine group is replaced with a sulfobetaine group or a carboxybetaine group can also be used as described above.

[0041] The monomer unit B preferably has the following formula (II): and has a structure represented by R ３ represents a linear or branched alkyl having 1 to 5 carbon atoms, preferably a linear alkyl having 1 to 5 carbon atoms, more preferably a methyl group, and R ４ represents a direct bond, a linear or branched alkylene having 1 to 5 carbon atoms, preferably a direct bond or a linear alkylene having 1 to 5 carbon atoms, more preferably a direct bond. In the formula (II), the succinimidyl group portion may be substituted with an arbitrary substituent.

[0042] From the viewpoint of the ease of forming a hydrogel, the ratio of the monomer unit A to the monomer unit B in the copolymer is preferably 20:80 to 80:20, more preferably 30:70 to 70:30, still more preferably 40:60 to 60:40 in terms of molar ratio.

[0043] In the formulas (I) and (II), preferably, R １ is a methyl group, R ２ is a methylene group, R ３ is a methyl group, and R ４ is a direct bond. In this case, the copolymer composed of the monomer units A and B has the following structure: The structure has the following characteristics, in which m and n represent the relative abundance of each monomer unit in the polymer, and independently represent integers of 2 or more, but each can be 2000 or less, preferably 1000 or less.

[0044] The weight-average molecular weight (Mw) of the copolymer is not particularly limited, but is preferably 5,000 to 1,000,000, more preferably 10,000 to 1,000,000, and even more preferably 50,000 to 1,000,000.

[0045] Electron transfer mediator compounds are compounds that possess redox electrons capable of mediating electron transfer. Examples of electron transfer mediator compounds include cyclopentadienyl metal complexes having an amino group, or quinone compounds having an amino group, such as aminoferrocene and amino-3-chloro-1,4-naphthoquinone.

[0046] Enzymes are catalytic proteins produced by living organisms. An example is glucose oxidase (GOD), an enzyme catalyst used in biofuel cells that use glucose as fuel. Other examples include enzymes, aptamers, and antibodies that recognize biomarkers for sensors measuring health status, biomarkers for measuring diseases and pathological conditions such as glucose, lactic acid, alcohol, and cancer, and biomarkers for measuring stress.

[0047] As described above, the N-succinimide ester group in monomer unit B reacts with the amino group in the protein or electron transfer mediator compound to form a covalent bond (amide bond), thereby enabling the stable immobilization of the molecular recognition material in the hydrogel.

[0048] Hydrogels are, for example, gels of copolymers of 2-methacryloyloxyethyl phosphorylcholine (MPC) and N-hydroxysuccinimide methacrylate (MNHS). MPC can have zwitterionic functional groups and can form water-containing hydrogels.

[0049] This disclosure also relates to a method for manufacturing an electrochemical device, which includes creating a flexible, nonwoven fiber sheet by electrospinning, forming a metal plating film on the surface of the fibers contained in the fiber sheet by electroless plating to make the fiber sheet conductive, preparing a hydrogel, and combining the conductive fiber sheet and the hydrogel to obtain an electrochemical device.

[0050] Fiber sheets can be formed using the electrospinning method. Electrospinning is performed using a solution of fiber raw materials mixed with a solvent, and a fiber sheet can be created on a conductive substrate such as aluminum foil. Conventional electrospinning equipment can be used.

[0051] The raw material for the fiber is a polymer, and the diameter of the fiber can be adjusted by changing the molecular weight of the polymer.

[0052] The molecular weight of the polymer used as a raw material for electrospinning can depend on the type of raw material and the shape of the fiber to be formed. Depending on the electrospinning apparatus, for example, if the raw material is PLA, a weight-average molecular weight (Mw) of 150,000 or more, or 200,000 or more, is preferable. Having the above-mentioned preferred molecular weight of PLA allows for better formation of the fiber structure when the film is formed by electrospinning.

[0053] The solvent used to dissolve the raw materials for the fibers used in electrospinning can be one that suits the type of raw material and the shape of the fiber to be formed. For example, if the raw material is PLA, the solvent can be 2,2,2-trifluoroethanol (TFE).

[0054] The amount of fiber raw material mixed with the solvent can depend on the type of raw material and the shape of the fiber to be formed. Depending on the electrospinning apparatus, for example, if the raw material is PLA, the ratio of the raw material to the total amount of solvent and raw material is, for example, 3 to 25% by mass, 4 to 20% by mass, 5 to 15% by mass, or 6 to 10% by mass. By including PLA in the solvent in the above example amounts, a PLA fiber sheet with better flexibility can be formed.

[0055] The electrospinning conditions can be set according to the composition of the fiber sheet to be created. The diameter of the fabricated fiber and the fiber sheet density can be controlled by the electrospinning conditions such as the solvent, polymer concentration (viscosity), distance between the nozzle and electrode, and applied voltage. In addition, the thickness of the fiber sheet can be controlled by the electrospinning spray time. Figure 16 shows SEM images of fibers fabricated with PLA solution concentrations of (a) 6.7 mass%, (b) 8 mass%, and (c) 10 mass%.

[0056] Electroless plating is used to form a metal plating film on the surface of the fibers contained in the fiber sheet, thereby giving the fiber sheet conductivity. Preferably, the conductive film is formed by electroless plating. By performing electroless plating, it is possible to form a conductive film on the surface and the surface of the fibers inside the three-dimensional structure without substantially blocking the voids between the fibers in the nonwoven fabric structure in which the fibers are stacked three-dimensionally. As a result, a fiber sheet can be obtained in which both the surface and the interior of the nonwoven fabric structure are conductive.

[0057] In electroless plating, a pretreatment to impart a catalyst may be performed using conventional methods. For example, a pretreatment in which platinum colloid is adsorbed onto the fiber by electrostatic interaction can be performed. The charging method is not particularly limited, but for example, the fiber sheet may be charged by immersing it in a stearyltrimethylammonium chloride (STAC) solution. The platinum colloid adsorption method is not particularly limited, but for example, the charged fiber sheet may be immersed in a platinum colloid solution to adsorb platinum particles onto the fiber surface.

[0058] Electroless plating is used, for example, with HAuCl ４ and H ２ O ２ This can be done using a plating bath of a mixed solution.

[0059] To improve the adhesion strength between the fiber and the metal plating film formed by electroless plating, the electroless plated fiber sheet may be heat-treated. The heat treatment temperature is preferably 100°C to 130°C. By heat-treating at the above preferred temperature, the adhesion strength between the fiber and the metal plating film can be further improved.

[0060] (Preparation of hydrogels) The synthesis of copolymers, including the preparation of monomer compounds and their polymerization, can be carried out by conventional methods based on the level of skill of those skilled in the art. For example, known methods such as radical polymerization, living radical polymerization, cationic polymerization, anionic polymerization, or solution polymerization, emulsion polymerization, and suspension polymerization can be used for the synthesis of copolymers.

[0061] As polymerization initiators in radical polymerization, any substance that decomposes and generates radicals in the reaction temperature range of 30 to 90°C can be used without particular restrictions. Specific examples of such polymerization initiators include, for example, 2,2-azobis(2-amidinopropyl) dihydrochloride, 4,4-azobis(4-cyanovaleric acid), 2,2-azobis(2-(5-methyl-2-imidazolin-2-yl)propane) dihydrochloride, 2,2-azobisisobutylamide dihydrate, 2,2-azobisisobutyronitrile, ammonium persulfate, potassium persulfate, benzoyl peroxide, succinate peroxide, diisopropyl peroxydicarbonate, t-butylperoxy-2-ethylhexanoate, t-butylperoxypivalate, t-butylperoxydiisobutyrate, lauroyl peroxide, azobisisobutyronitrile, 2,2-azobis(2,4-dimethylvaleronitrile), t-butylperoxyneodecanoate, and the like. Preferably, it is 2,2-azobisisobutyronitrile.

[0062] From the viewpoint of polymerization efficiency, the concentration of monomers in the polymerization reaction solution is preferably 0.1 M to 5 M in total. Any solvent capable of dissolving each monomer can be used in the polymerization reaction, but chloroform is preferred from the viewpoint of gelation efficiency. The reaction temperature is usually in the range of 30 to 90°C, and particularly preferably 40 to 59°C.

[0063] The bonding between the hydrogel and the molecular recognition material is a chemical bond, preferably a covalent bond. This bonding can be achieved by mixing the hydrogel and the molecular recognition material and then drying them.

[0064] The bonding of the hydrogel and the electron transfer mediator can be achieved by mixing the hydrogel and the electron transfer mediator and drying them. After drying, ethanol washing and heat treatment at 90-120°C may be performed as desired.

[0065] Enzymes can be immobilized on hydrogels to which electron transport mediators are attached. Immobilization of enzymes on hydrogels to which electron transport mediators are attached can be done by physical or chemical binding to the hydrogel.

[0066] Physical binding can be obtained by mixing and drying a solution of a hydrogel to which an electron transfer mediator is bound with an enzyme. By mixing and drying a solution of a hydrogel to which an electron mediator is bound with an enzyme, a hydrogel can be obtained in which the enzyme is physically captured and bound within the hydrogel.

[0067] Chemical bonding can be achieved by chemically crosslinking an enzyme to, for example, an amino group of a hydrogel to which an electron transfer mediator is attached, thereby obtaining a hydrogel to which an enzyme is chemically bonded.

[0068] Figure 9 shows photographs of hydrogel membranes with physically bound enzymes and hydrogel membranes with chemically bound enzymes, held with tweezers. Figure 9(A) is a photograph of the hydrogel membrane with physically bound enzymes, and Figure 9(B) is a photograph of the hydrogel membrane with chemically bound enzymes.

[0069] (Combination of fiber sheet and hydrogel) Preferably, combining a conductive fiber sheet with a hydrogel involves pressing the hydrogel into the conductive fiber sheet to physically hold the hydrogel in the gaps of the nonwoven fabric structure of the conductive fiber sheet. Pressing the hydrogel into the fiber sheet can be done manually with fingers or with a device such as a press. The hydrogel can be pressed into gaps of the nonwoven fabric structure of the fiber sheet ranging in size from nanometers to micrometers. Pressing the hydrogel into the gaps of the fiber sheet is easier if the hydrogel is an aggregate of gel particles ranging in size from nanometers to micrometers with a diameter similar to or smaller than the dimensions of the gaps in the fiber sheet.

[0070] Preferably, combining a conductive fiber sheet with a hydrogel involves chemically bonding the conductive fiber sheet and the hydrogel. Chemical bonding includes adsorption (adhesion).

[0071] (Example 1) (Formation of Fiber Sheet) Using 2,2,2-trifluoroethanol (TFE) as the solvent, a solution was prepared by mixing 8% by mass of PLA with a molecular weight of 200,000 or more with the solvent. Using this solution as the raw material, an electrospinning method (manufactured by KatoTech, NEU) was performed to form a PLA fiber sheet on aluminum foil. The electrospinning conditions were 30-40% humidity, room temperature, distance 100 mm, syringe speed 0.3 mm / min, voltage 15 kV, and 24 hours. The thickness of the formed PLA fiber sheet was adjusted to approximately 75 μm.

[0072] Figure 1 shows a photograph of the appearance of a PLA fiber sheet formed on aluminum foil. Figure 2 shows an SEM image (JCM-7000 NeoScope®, JEOL) of the formed PLA fiber sheet. The PLA fiber sheet has a nonwoven fabric structure, and the average diameter of the PLA fibers constituting the sheet was 533 nm. Figure 16 shows SEM images of fibers prepared using (a) 6.7 mass%, (b) 8 mass%, and (c) 10 mass% PLA solutions.

[0073] (Electroless Plating) The formed PLA fiber sheet was immersed in a 0.1% stearyltrimethylammonium chloride (STAC) solution for 1 minute to positively charge the PLA fiber. Next, the charged PLA fiber was plated with a platinum colloid solution (0.05 mM H₂ in deionized water). ２ PtCl ６ -6H ２ 0, 2 mg / mL PVP, and 2 μM NaBH ４ The PLA fiber was immersed in a solution for one minute to pre-treat it by depositing platinum nanoparticles onto the PLA fiber surface through electrostatic interaction.

[0074] Next, 10 mM HAuCl ４ and 20 mM H ２ O ２ Using a plating bath prepared with the mixed solution, electroless Au plating was performed on a pre-treated PLA fiber sheet for 15 minutes to form an Au plating (Au film) on the platinum nanoparticles on the surface of the fiber, thereby forming an Au / PLA fiber sheet.

[0075] To improve the adhesion strength between the PLA fiber and the Au plating, the Au / PLA fiber sheet was heat-treated at 130°C for 60 minutes.

[0076] The formed Au / PLA fiber sheet had a thickness of approximately 100 μm and was flexible. The average diameter of the Au-plated fibers in the Au / PLA fiber sheet was approximately 900 nm, and the thickness of the Au plating was approximately 200 nm. The formed Au / PLA fiber sheet had a nonwoven fabric structure with voids, as shown in Figure 3.

[0077] The formed Au / PLA fiber sheet is 8.3 × 10 ５ The electrode exhibited a conductivity of S / m and a resistance of 0.002 Ω, demonstrating sufficient electrical properties for use as an electrode in an electrochemical device. Conductivity was measured using the four-probe method (Loresta-GX II MCP-T710), and resistivity was measured using the two-probe method.

[0078] Figure 7 shows the Au / PLA fiber sheet prepared as an electrode and 10 mM Fe[CN] as the electrolyte. ６ ] ３－／４－ The results of 255 cycles of cyclic voltammetry performed using [the specified method] are shown. The fabricated Au / PLA fiber sheet was found to have sufficient stability for electrochemical property measurement.

[0079] (Preparation of hydrogel) 2-methacryloyloxyethyl phosphorylcholine (MPC) and N-hydroxysuccinimide methacrylate (MNHS) were used as monomer units.

[0080] A copolymer poly (MPC-co-MHNS) was synthesized by a radical polymerization reaction commonly used in the art, using 0.5 mol / L MPC and 0.5 mol / L MNHS with 0.33 mol / L 2,2'-azobisisobutyronitrile (AIBN) as a polymerization initiator. The reaction time was 24 hours and the reaction temperature was 59°C. Chloroform was used as the solvent.

[0081] Hydrogel formation was observed in the synthesized copolymer Poly (MPC-co-MHNS). Initially, the reaction solution was clear after mixing each monomer and polymerization initiator, but it became cloudy as the polymerization reaction progressed. Scanning electron microscopy (SEM) was used to measure the morphology of the gel particles constituting the hydrogel dispersed in the aqueous solution after drying. A large number of particles with a diameter of 1 μm or more were found. After the polymerization reaction was complete, the precipitated product was dried under reduced pressure to remove the solvent, yielding white powder Poly (MPC-co-MHNS).

[0082] (Immobilization of electron transfer mediator compounds) The obtained Poly(MPC-co-MHNS) was immobilized with aminoferrocene (AFc), an electron transfer mediator compound, by the method shown below. The reaction equation is as follows.

[0083] (Reaction with organic solvent) Aminoferrocene (AFc) was dissolved in ethanol, and the resulting Poly (MPC-co-MHNS) and triethylamine as a catalyst were added to the solution. The mixture was stirred overnight at room temperature to obtain a hydrogel, which was a black product (Gel / AFc).

[0084] The enzyme was physically immobilized on a ferrocene-immobilized hydrogel (Gel / AFc) obtained by reaction with an organic solvent using the following method. The Gel / AFc washed with ethanol was vacuum-dried overnight to remove residual ethanol. Next, the vacuum-dried Gel / AFc was immersed in a 50 mg / ml glucose oxidase (GOD) solution to obtain an enzyme-encapsulated hydrogel (Gel / AFc / GOD). This was stored at 4°C.

[0085] (Compositing of Au / PLA fiber sheet and hydrogel) An enzyme-encapsulated hydrogel (Gel / AFc / GOD) with an immobilized enzyme was pressed into the formed Au / PLA fiber sheet with a finger, and an electrochemical device containing an Au / PLA fiber sheet was fabricated in which the enzyme-encapsulated hydrogel was physically held in the gaps of the nonwoven fabric structure of the Au / PLA fiber sheet.

[0086] Figure 10(B) shows an external view of the device, which was fabricated by embedding an enzyme-encapsulated hydrogel (Gel / AFc / GOD) with the enzyme physically immobilized in the gap of a three-dimensional nonwoven fabric structure at one end of a strip-shaped Au / PLA fiber sheet covered in polyimide tape in the center. Figure 10(A) shows a strip-shaped Au / PLA fiber sheet covered in polyimide tape in the center.

[0087] (Comparative Example 1) A flat PLA sheet with a thickness of approximately 1 mm was prepared. Electroless Au plating was performed on the flat PLA sheet to form an Au plating (Au film) on its surface. An enzyme-encapsulated hydrogel (Gel / AFc / GOD) obtained by the same method as in Example 1 was applied to the Au-plated flat PLA sheet to fabricate an electrochemical device.

[0088] (Reference Examples 1-4) Hydrogel formation was attempted under the same conditions as in Example 1, except that the monomer ratios of the molar concentrations of MPC and MNHS were 1:9, 3:7, 7:3, and 9:1 (Reference Example 1). In Reference Examples 2 and 3, hydrogels containing particles with a diameter of 1 μm or more, similar to those in Example 1, were obtained. Table 1 shows whether hydrogel formation was possible in Example 1 and Reference Examples 1-4.

[0089]

[0090] (Characterization) Figures 3 and 4 show SEM images and EDX elemental analysis results of the surface of an Au / PLA fiber sheet with an Au film formed on the surface of the PLA fiber by electroless plating, and a PLA fiber sheet without plating. Figure 5 shows a photograph of the Au / PLA fiber sheet prepared in Example 1 being held with tweezers. Figure 6 shows the stress-strain curves of the Au / PLA fiber sheet prepared in Example 1 and a PLA fiber sheet without plating. The stress-strain curves were measured using a stress-strain tester (SHIMADZU EZ-SX 500N). The strain was slightly smaller in the fiber sheet with the Au film formed than in the fiber sheet without the Au film, but it still had sufficient flexibility.

[0091] Figure 8 shows the cyclic voltammetry (CV) results for the Au / PLA fiber sheet fabricated as an electrode in Example 1 and the Au-plated flat PLA sheet fabricated in Comparative Example 1. Sensitivity is important for use in electrochemical devices, especially sensors, and the current response of the Au / PLA fiber sheet fabricated in Example 1 was five times higher than that of the Au-plated flat PLA sheet fabricated in Comparative Example 1.

[0092] Figure 11 shows the 0.5 M H of a PLA fiber sheet prepared using the electrospinning method in Example 1 and a flat PLA plate that has been electrolessly plated with Au in Comparative Example 1. ２ SO ４ A graph comparing the CV characteristics inside is shown. Without adding ferrocene as an oxidation-reduction pair, H ２ SO ４ The amount of Coulombs was measured inside. The PLA fiber sheet with electroless plating had a larger electrode area, resulting in a higher current value.

[0093] The CV characteristics of the electrochemical devices prepared in Example 1 and Comparative Example 1 were evaluated. Figure 12 shows the CV curve of the glucose response observed 3 days after immersion of the electrochemical device prepared in Example 1 in a solution of 5 mM glucose dissolved in phosphate-buffered saline (PBS). Figure 13 shows the CV curve of the glucose response observed 2 days after immersion of the electrochemical device prepared in Comparative Example 1 in a solution of 5 mM glucose dissolved in PBS. In Figure 12 or Figure 13, the CV measurement results when the electrochemical device was immersed in phosphate-buffered saline (PBS) are shown as a reference example.

[0094] Table 2 shows the glucose-catalyzed oxidation current at 0.34 V for the CV curve shown in Figure 12 or Figure 13.

[0095] The enzyme electrode prepared in Example 1 showed a slight decrease in current value one day after immersion compared to the initial state, but the current value remained stable until three days later. The electrochemical device prepared in Comparative Example 1 had a low current value from the time of immersion and also exhibited poor long-term stability. Thus, comparing the electrochemical device prepared using plate PLA in Comparative Example 1 with the electrochemical device prepared using fiber PLA in Example 1, it can be seen that Example 1, which used fiber PLA and held Gel / AFc / GOD in the gaps of the Au / PLA fiber sheet, obtained approximately 12 times the reaction current and was able to detect glucose with good sensitivity.

[0096] Figure 14 shows photographs of the electrochemical device fabricated in Example 1 when bent to 0, 45, and 90 degrees in a 5 mM glucose solution. Figure 15 shows the CV curves measured while the electrochemical device was bent at the above angles in a 5 mM glucose solution. The fabricated electrochemical device showed a substantially constant reaction current regardless of the bending angle.

Claims

1. An electrochemical device comprising a fiber sheet having flexibility and conductivity and a nonwoven fabric structure, and a hydrogel, wherein the hydrogel is held in the gaps of the nonwoven fabric structure of the fiber sheet.

2. The electrochemical device according to claim 1, wherein the hydrogel has a molecular recognition substance comprising an electron transfer mediator, an enzyme, an aptamer, an antibody, or a combination thereof.

3. The electrochemical device according to claim 1, wherein the fiber sheet has a conductive film on the surface of the fibers constituting the fiber sheet.

4. The electrochemical device according to claim 3, wherein the conductive film is a noble metal film.

5. The electrochemical device according to claim 3, wherein the conductive film is a metal plating film.

6. The electrochemical device according to claim 3, wherein the conductive film is an Au plated film or a Pt plated film.

7. The electrochemical device according to claim 1, wherein the fibers constituting the fiber sheet have an average diameter of 50 nm or more and less than 1000 nm.

8. The electrochemical device according to claim 3, wherein the conductive film has an average thickness of 10 to 300 nm.

9. The electrochemical device according to claim 1, wherein the fibers constituting the fiber sheet are polylactic acid (PLA), polyester, polyamide, polyurethane, or a combination thereof.

10. The electrochemical device according to claim 1, wherein the hydrogel is a zwitterionic polymer hydrogel.

11. The electrochemical device according to claim 1, wherein the hydrogel is formed from a copolymer comprising monomer unit A having a zwitterionic group in its side chain and monomer unit B having an N-succinimide ester group in its side chain as repeating units.

12. An electrochemical device according to any one of claims 1 to 11, which is an electrochemical sensor, a biosensor, a transducer, a biofuel cell, a drug delivery carrier, or an electrode thereof.

13. A method for manufacturing an electrochemical device, comprising: creating a fiber sheet having flexibility and a nonwoven fabric structure by electrospinning; forming a metal plating film on the surface of the fibers contained in the fiber sheet by electroless plating to give the fiber sheet conductivity; preparing a hydrogel; and combining the conductive fiber sheet and the hydrogel to obtain an electrochemical device.

14. A method for producing an electrochemical device according to claim 13, comprising combining the hydrogel with a molecular recognition substance comprising an electron transfer mediator, an enzyme, an aptamer, an antibody, or a combination thereof.

15. A method for manufacturing an electrochemical device according to claim 13 or 14, wherein combining the conductive fiber sheet and the hydrogel includes physically holding the hydrogel on the conductive fiber sheet.

16. A method for manufacturing an electrochemical device according to claim 13 or 14, wherein combining the conductive fiber sheet and the hydrogel includes chemically bonding the conductive fiber sheet and the hydrogel.

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