Reference electrode, electrode, and sensor comprising the same

Abstract

To provide a novel electrode or the like for detecting or measuring albumin in a sample solution. [Solution] An electrode for detecting or measuring albumin in a sample solution, comprising an ionic liquid-containing membrane.

Description

Technical Field

[0001] The present invention relates to a reference electrode, an electrode, and a sensor including these electrodes.

Background Art

[0002] An electrochemical sensor includes, in addition to a working electrode, a reference electrode that serves as a reference for measuring the potential of the working electrode. Conventionally, as a reference electrode, for example, an electrode material made of Ag / AgCl is immersed in an internal solution made of a high-concentration KCl solution, and the electrode material and the internal solution are accommodated in a container having a liquid junction portion such as ceramics or glass.

[0003] In the reference electrode as described above, it is common that the internal solution contacts the sample solution through the liquid junction portion. In such a reference electrode, K and Cl always move toward the sample solution side due to a concentration gradient or the like, resulting in problems such as contamination of the sample solution, clogging of the liquid junction portion, and the need to replenish or replace the internal solution. As a means for solving such problems, for example, Patent Document 1 discloses a reference electrode including an internal electrode, an internal solution contacting the internal electrode, and a liquid junction portion continuous with the internal solution, wherein the liquid junction portion uses a gelled ionic liquid. + and Cl -

[0004]

Prior Art Documents

Patent Documents

[0005] [Patent Document 1] Patent No. 4733588 [Patent Document 2] International Publication No. 2021 / 140933 [Overview of the Initiative] [Problems that the invention aims to solve]

[0006] In electrochemical sensors, the electrode potential of the reference electrode depends on the type of sample being tested, the analyte, and / It is desirable that the concentration of the component remains constant regardless of the concentration of other components, especially in living tissue such as serum. Since the sample contains various components including proteins, when measuring biological samples, It is necessary to provide a reference electrode that exhibits a stable electrode potential unaffected by such components. Yes, they are.

[0007] The inventors have found that in the above-mentioned Patent Documents 1 and 2, which use ionic liquids, albumin in biological samples We discovered that the potential fluctuates due to the influence of albumin. Therefore, the present invention is designed to address the influence of albumin. A novel reference electrode that exhibits a stable electrode potential even when measuring biological samples, without any issues. The objective is to provide sensors and other devices equipped with this feature. [Means for solving the problem]

[0008] A reference electrode according to one embodiment of the present invention comprises an ionic liquid-containing film and on the ionic liquid-containing film It comprises a hydrophilic film arranged therein. In this embodiment, the reference electrode is equipped with an ionic liquid-containing film, so the components inside the reference electrode are the electrode Leakage to the outside is suppressed. Furthermore, a hydrophilic film is placed on top of the ionic liquid-containing film. Therefore, the ionic liquid-containing membrane becomes less likely to come into contact with the biological sample, and albumin in the biological sample becomes less likely to come into contact with the biological sample. The effect on the surface state of the ionic liquid-containing film can be reduced. Also, ionic liquids Due to its low solubility in water, the concentration of the ionic liquid rapidly increases at the interface between the hydrophilic film and the ionic liquid-containing film. The degree becomes constant and reaches an equilibrium state, and the interlibrium potential difference is smaller compared to conventional reference electrodes. This makes it possible to provide a reference electrode that exhibits a stable electrode potential even when measuring biological samples. Cut.

[0009] In the above embodiment, the ionic liquid-containing membrane preferably comprises the internal components of the reference electrode. It is configured to be isolated from the outside. This prevents components inside the reference electrode from flowing outside the electrode. This further suppresses the release of liquids and also reduces the interlibrary potential difference.

[0010] In any of the above embodiments, the hydrophilic film preferably contains a hydrophilic polymer. The molecule contains at least one selected from the group consisting of polysaccharides and their crosslinked products. Polyvinyl alcohol, polyethylene oxide, sodium polyacrylate, and Polymethyl methacrylate, and acrylamide, 2-methacryloyloxyethyl phosphate Polymers containing monomer units derived from holylcholine or myristyl alcohol, and It comprises at least one selected from the group consisting of derivatives thereof and crosslinked forms thereof. This may also be the case. If the hydrophilic film is in the above configuration, the components in the biological sample will be on the surface of the ionic liquid-containing film. This can reduce the impact on the state.

[0011] The above polysaccharides are preferably pullulan, cellulose, pectin, acarbose, and amylop Kuchin, inulin, chitin, chitosan, β-glucan, glycogen, α-cyclodextrin Phosphorus, β-cyclodextrin, γ-cyclodextrin, stachyose, dextran , dextrin, maltotriose, mannan, melegitose, raffinose, and leva Selected from the group consisting of , and derivatives thereof. When these polysaccharides are used, living organisms This makes it possible to reduce the influence of components in the sample on the surface state of the ionic liquid-containing film. .

[0012] The above hydrophilic polymer is preferably water-soluble. According to this embodiment, the hydrophilic film is used in biological samples. Because the sample gradually dissolves during measurement, the surface of the hydrophilic membrane is constantly contaminated with components of the biological sample. This makes it possible to achieve a situation where there is no need for a reference electrode. Therefore, the reference electrode in this embodiment is used when measuring biological samples. This allows for even more stable electrode potential.

[0013] In any of the above embodiments, the average thickness of the hydrophilic film is preferably 1 μm or more. It is 00 μm or less. According to this embodiment, the electrode is even more stable when measuring biological samples. It can provide electrical potential.

[0014] In any of the above embodiments, the hydrophilic film consists of two or more layers with different compositions. This may also be the case. According to this embodiment, the electrode potential is even more stable when measuring biological samples. We can provide this.

[0015] In any of the above embodiments, the ionic liquid-containing membrane preferably contains an ionic liquid It is a gel film. According to this embodiment, the electrode is even more stable when measuring biological samples. It can provide electrical potential.

[0016] A reference electrode according to one embodiment of the present invention comprises an internal electrode and an electrode disposed on the internal electrode. A solid electrode comprising an internal solid layer, wherein the ionic liquid-containing film is located on the internal solid layer. It may be arranged in a certain position. According to this embodiment, a solid-type reference electrode can be provided. .

[0017] The above-mentioned internal solid layer preferably includes an insertion material and ion-conducting ceramics. It possesses. According to this embodiment, a time-stable electrode potential can be provided.

[0018] The above insertion material is preferably a metal oxide, an oxygen redox material, or a prussian. It is an ambrou analog. Furthermore, the above metal oxide is preferably M x MnO2(M is Na or ) represents K, and x represents any positive number. Furthermore, the above ion-conducting ceramics Preferably, it is β'' alumina or β-alumina. According to this embodiment, time-stable It can provide electrode potential.

[0019] A reference electrode according to another embodiment of the present invention comprises an internal electrode and an internal electrode into which the internal electrode is immersed. The device further comprises a liquid, an internal electrode and a housing that contains the internal liquid, and the housing is a liquid junction The liquid junction portion has a section, and the ionic liquid is separated from the internal liquid and the sample solution in the liquid junction portion. A body-containing membrane is arranged, and the hydrophilic membrane is located on the sample solution side of the ionic liquid-containing membrane. This embodiment provides a reference electrode having an internal liquid.

[0020] A sensor according to one embodiment of the present invention comprises an insulating substrate and a third disposed on the insulating substrate. The device comprises an electrode 1 and an electrode 2, wherein the first electrode comprises an ionic liquid-containing membrane and the ionic liquid It comprises a hydrophilic film disposed on a liquid-containing film. In this embodiment of the sensor, the first electrode has an ionic liquid-containing film, so the inside of the first electrode The leakage of these components to the outside of the electrode is suppressed. In addition, a hydrophilic film is formed on the ionic liquid-containing film. Because of their arrangement, the ionic liquid-containing membrane is less likely to come into contact with the biological sample, and the seeds in the biological sample This makes it possible to reduce the influence of each component on the surface state of the ionic liquid-containing film, and also the The liquid-liquid potential difference at electrode 1 is suppressed. This ensures stable measurement even when measuring biological samples. We can provide a sensor that can measure accurately.

[0021] The above sensor preferably has the electrode at the second electrode with respect to the first electrode. This is a sensor that measures electric potential. Furthermore, the sensor has a current flowing between the first electrode and the second electrode. It may also be a sensor that measures the current being drawn.

[0022] In any of the above sensors, the first electrode preferably relates to any of the above embodiments. This is a reference electrode. In any of the above sensors, the second electrode is an aluminum in the following sample solution. It may be an electrode for detecting or measuring bumin.

[0023] In any of the above sensors, the first electrode and the second electrode are connected to an internal electrode. An electrode comprising an internal solid layer disposed on the internal electrode, wherein the first electrode In this arrangement, the ionic liquid-containing film is placed on the internal solid layer, and the internal electrode and the internal It is preferable that the solid layer of the first electrode and the second electrode are substantially identical. Such sensors are easier to manufacture, resulting in lower manufacturing costs, and also have an internal solid layer. Even if the interfacial potential of the electrodes changes over time, the change is not reflected in the first electrode and the second electrode. Because the effects cancel each other out, more stable measurements can be obtained over time.

[0024] In any of the above sensors, the second electrode detects albumin in the following sample solution or The first electrode and the second electrode are electrodes for measurement, and the first electrode and the second electrode are internal electrodes and the An electrode comprising an internal solid layer disposed on an internal electrode, the first electrode and the upper In the second electrode, the ionic liquid-containing film is placed on the internal solid layer, and the internal The electrode, the internal solid layer, and the ionic liquid-containing film are the first electrode and the second electrode and Therefore, it is preferable that they be substantially identical. Such sensors can be easily manufactured. The manufacturing cost is lower, and the interface potential between the internal solid layer and the electrode, and / or between the internal solid layer and the ion Even if the interfacial potential of the liquid-containing film changes over time, the first electrode and the second electrode will not change Because the changes cancel each other out, more stable measurements can be obtained over time.

[0025] An electrode according to one embodiment of the present invention is for detecting or measuring albumin in a sample solution. An electrode comprising an ionic liquid-containing membrane. The electrode in this embodiment is used with antibodies or antibodies that are typically used to specifically recognize albumin. Contains aptamers that mimic the structure, molecularly imprinted polymers, or albumin-labeled dyes, etc. Even without this, albumin in the sample solution can be detected or measured. [Effects of the Invention]

[0026] According to the present invention, a novel reference electrode exhibits a stable electrode potential even when measuring biological samples. We can also provide sensors and other devices equipped with this. [Brief explanation of the drawing]

[0027] [Figure 1] This is a schematic cross-sectional view of a reference electrode according to one embodiment of the present invention. [Figure 2] This is a schematic cross-sectional view of a reference electrode according to another embodiment of the present invention. [Figure 3] This is a schematic cross-sectional view of a reference electrode according to yet another embodiment of the present invention. [Figure 4] This is a schematic cross-sectional view of an albumin measurement electrode according to one embodiment of the present invention. [Figure 5] (A) A schematic plan view and (B) A schematic cross-sectional view taken along the line X-X' of a sensor according to one embodiment of the present invention. [Figure 6] This is a schematic cross-sectional view of the method of using a sensor according to one embodiment of the present invention. [Figure 7] This is a schematic cross-sectional view of the electrode potential measurement method in the example. [Figure 8] This figure shows the amount of potential shift in an electrode with an ionic liquid-containing membrane due to albumin or γ-globulin. [Figure 9] This figure shows the relationship between albumin concentration and the potential shift of an electrode with an ionic liquid-containing membrane. [Figure 10] This figure shows the amount of potential shift when the content and type of ionic liquid are changed. [Figure 11] This figure shows the potential shift ΔE, which is the difference between the measurement potential E of the albumin solution at each electrode and the measurement potential Ebase of the buffer solution that does not contain albumin. [Figure 12] This is a diagram showing the measurement system. [Figure 13] This figure shows the measurement results of standard serum using a potassium ion sensor. [Figure 14] This figure shows a calibration curve created using an albumin sensor. [Figure 15] This figure shows the pH meter results of an albumin-containing solution. [Modes for carrying out the invention]

[0028] The following describes embodiments for carrying out the present invention with reference to the drawings (hereinafter referred to as "this embodiment"). The present invention will be explained in detail, but is not limited thereto, and will deviate from its essence. Various deformations are possible within the limits. In the following drawings, the same or similar parts These are represented by the same or similar symbols. The drawings are schematic and do not necessarily reflect the actual situation. Dimensions and proportions may not match. Even between drawings, the relationships between dimensions and proportions may differ. It may contain minutes.

[0029] [First Embodiment: Solid-State Reference Electrode] Figure 1 is a schematic cross-sectional view of the reference electrode of this embodiment. As shown in Figure 1, The reference electrode 100 consists of an internal electrode 102 and an internal solid layer 1 located on the internal electrode 102. 04, and an ionic liquid-containing film 106 disposed on the internal solid layer 104, and an ionic liquid-containing It comprises a hydrophilic film 108 disposed on a film 106. The reference electrode 100 is a component This is a solid-type reference electrode that does not require a liquid, or rather, a fluid, internal liquid.

[0030] In this specification, a reference electrode is used to provide a reference for potential when measuring electrode potential. This is an electrode that is electrically connected to the working electrode in sensors and electrochemical cells. It is used in this way, and the electrode potential of the working electrode is output as the potential difference between the reference electrode and the working electrode. Furthermore, typically, the reference electrode is used in such a way that almost no current flows through it. The reference electrode must have a reversible electrode reaction and exhibit minimal fluctuations in electrode potential during use. This is required.

[0031] Because the reference electrode 100 has the above configuration, the ionic liquid-containing film 106 and hydrophilicity are particularly important. Because it has membrane 108, it exhibits a stable electrode potential even when measuring biological samples. The structure will be described in detail.

[0032] (Internal electrode) The internal electrode 102 is a conductive material and is connected to a desired material including the working electrode. This is a component for electrically connecting the internal solid layer 104.

[0033] The internal electrode 102 is, for example, an electrode containing a conductive material. The conductive material is, in particular, Examples include platinum, gold, silver, copper, carbon, palladium, chromium, and aluminum. Metals such as um and nickel, alloys containing at least one of these metals, and these Examples include metal halides. The conductive material is preferably platinum, gold, silver, or palladium. The conductive material is at least one of aluminum, nickel, and carbon. Alternatively, two or more types may be used in combination.

[0034] In the above embodiment, the content of conductive material in the internal electrode 102 is the total mass of the internal electrode. For example, it is 70-100% by mass (including both extreme values; not specifically mentioned in this specification). The same applies except in the case of ( ), preferably 85-100% by mass, more preferably 95- It is 100% by mass. Note that a conductive material content of 100% by mass means that the internal electrode 1 This means that 02 consists only of conductive material.

[0035] In Figure 1, the internal electrode 102 is shown as a single layer, but the internal electrode 102 is a single It may be a single-layer structure consisting of the above composition, or it may include two or more layers having different compositions. A multi-layered structure is also acceptable.

[0036] The average thickness of the internal electrodes 102 is not particularly limited, as long as the conductivity is not significantly impaired. The thickness is, for example, 1 to 10 μm, preferably 1 to 5 μm. Internal electrode 10 When component 2 has a thickness within the above range, manufacturing efficiency, manufacturing costs, etc. tend to improve. In this specification, the average thickness of each component in the electrode is measured by scanning electron microscopy or optical microscope when measuring the cross-section of the electrode. The measurement was taken by observation using a mirror, or by using a stylus-type surface shape measuring instrument, step meter, or radar. Measured using a displacement meter.

[0037] Furthermore, in the reference electrode 100, the internal electrode 102 is omitted, and the internal solid layer 104 is used. It may be directly connected to desired components, including electrodes. In the embodiment shown in Figure 1, the internal solid layer 104 is directly positioned on the internal electrode 102.

[0038] In the reference electrode 100, the side surface of the internal electrode 102 is covered with another material, and the internal electrode 10 The side of 2 may be configured so that it is not exposed. The side 102a of the internal electrode 102 is an insulator. It may be sealed with a coating member having an edge, or the internal electrode 102 may be in the internal solid layer 10 It is embedded in 4, and only the bottom surface 102b of the internal electrode 102 is exposed from the internal solid layer 104. It may be configured in this way.

[0039] (internal solid layer) The internal solid layer 104 is a solid layer containing a compound that undergoes a reversible oxidation-reduction reaction. The electrode potential of the reference electrode 100 is determined by the oxidation-reduction state of the compound. In addition to embodiments that essentially consist only of solid materials, the partial solid layer 104 may also consist of polymers. This also includes embodiments in which the matrix component contains a solvent and is gelled.

[0040] From the viewpoint of the reference electrode 100 exhibiting a more stable electrode potential, the internal solid layer 104 is internal solid It conducts ions involved in the oxidation-reduction reaction occurring in body layer 104 and is electrically conductive. Preferably. In this case, the compound that undergoes a reversible oxidation-reduction reaction is the ion involved in the reaction and Because electrons are supplied and released stably, the reference electrode 100 exhibits a more stable electrode potential. It tends to become like this. For example, the internal solid layer 104 undergoes a reversible oxidation-reduction reaction. In addition to the compound, it contains a substance that conducts ions involved in oxidation-reduction reactions, and a conductive agent. stomach.

[0041] The inner solid layer 104 is a compound that undergoes a reversible oxidation-reduction reaction, such as a metal chloride. or includes an insertion material, preferably including an insertion material. Examples of metal chlorides include silver chloride and mercury chloride. The material may be in particulate form, or it may be in a form that coats the surface of the internal electrode 102.

[0042] Insertion materials are materials that reversibly insert metal ions into their skeletal structure through oxidation-reduction reactions. It is a material that can be inserted and removed. The insertion material is capable of oxidation-reduction reactions. Due to the high inverse properties, the internal solid layer 104 contains an insertion material, which allows the reference electrode 1 to... 00 tends to show a more stable electrode potential, and the reproducibility between individuals is good. It tends to get more expensive.

[0043] From the perspective of further improving the stability of the reference electrode, the insertion material is an inorganic insertion material. It is a material. The ions that the insertion material inserts and removes are not particularly limited, but For example, sodium ions, potassium ions, lithium ions, calcium ions, magnesium Examples include sodium ions and the like. Among these ions, sodium ions and potassium ions are more preferred, and sodium ions are even more preferred.

[0044] Examples of the insertion material include, for example, metal oxides, oxygen redox materials, and Prussian blue analogs. Among these, metal oxides are preferred.

[0045] Examples of the metal oxide include, for example, M x MnO2, M x NiO2, M x CoO2, M x Ni 0.5 Mn 0. 5O2, M x FeO2, M x Fe 1 / 3 Mn 2 / 3 O2, M x Ni 1 / 3 Co 1 / 3 Mn 1 / 3 O2, M x Ni 0.5 Ti 0.5 O2, M x VO2, M x CrO2, and M x FePO4 and the like can be mentioned. In the above composition formula, M independently represents Na or K, and x represents an arbitrary positive number. The metal oxide is preferably M MnO2, and more preferably Na x MnO2. Using such a metal oxide, the reference electrode 100 tends to show a more stable electrode potential. x

[0046] In the above composition formula, x is usually a value greater than 0 and less than or equal to 1. x is preferably 0.1 50 to 0.660, more preferably 0.200 to 0.500, and even more preferably ​​​​The values ​​are 0.220-0.280, 0.300-0.360, or 0.410-0.470. Yes, and more preferably 0.245-0.255, 0.325-0.335, or 0 The range is 0.435 to 0.445.

[0047] The crystal structure of metal oxides is not particularly limited insofar as the insertion and removal of metal ions occur reversibly. No. Examples of crystal structures include orthorhombic, tetragonal, trigonal, hexagonal, and cubic. Examples include the orthorhombic system, triclinic system, and monoclinic system. Among these, the orthorhombic system is preferred. .

[0048] Oxygen redox materials utilize not only transition metals but also oxide ions in their oxidation-reduction reactions. It is a material that can do this. Examples of oxygen redox materials include Na2Mn3O7, Na 2 / 3 M g 0.28 Mn 0.72 O2, Na2PreO3, Na 1.3 Nb 0.3 Mn 0.4 O2 and Na 0.6 Li 0.2 M n 0.8 Examples include O2.

[0049] Prussian blue analogs are materials in which a cyano group is coordinated to a transition metal ion. Examples of ambreu analogs include Na2Mn[Fe(CN)6] and Na y CO[Fe(CN )6] 0.90 ·2.9H2O (wherein y represents any positive number), K-FeHCF (iron hexa Potassium cyanoferrate, K-NiHCF (Nickel hexacyanoferrate potassium), K-CuH CF (potassium copper hexacyanoferrate), Na-NiHCF (sodium nickel hexacyanoferrate) Examples include ammonium ions, and Ca-NiHCF (nickel hexacyanoferric iron calcium).

[0050] The insertion material may be included in the internal solid layer 104 in any form, but is preferable The particles are contained within. The shape of the particles is not particularly limited; for example, scales It may be cylindrical, columnar, spherical, or ellipsoidal, etc.

[0051] The above-mentioned insertion materials and their shapes can be used individually or in combination of two or more types. You may use it.

[0052] Compounds that undergo reversible oxidation-reduction reactions, such as metal chlorides and insertion materials, are particles When included in the internal solid layer 104 in one embodiment, the average particle size of the particles is preferably 1 to 20 μm. The particle size is m, more preferably 2 to 15 μm, and even more preferably 5 to 12 μm. Because the average particle size is within the above range, the metal salt is more uniformly distributed in the internal solid layer 104. This will include phosphates and insertion materials, and the oxidation-reduction reactions of these materials will This makes it easier to occur to a moderate degree. As a result, the reference electrode 100 exhibits a more stable electrode potential. It tends to be this way. Note that the above average particle size is measured using a laser diffraction / scattering particle size distribution analyzer. Just measure it.

[0053] Content of compounds that undergo reversible oxidation-reduction reactions, such as metal chlorides and insertion materials. This is, for example, 20 to 70 parts by mass with respect to 100 parts by mass of the total mass of the internal solid layer 104. Preferably 25 to 65 parts by mass, more preferably 30 to 60 parts by mass. In particular The content of the suction material is, for example, 2 parts by mass per 100 parts by mass of the total mass of the internal solid layer 104. The amount is 0 to 70 parts by mass, preferably 25 to 65 parts by mass, and more preferably 30 to 60 parts by mass. This is the mass part.

[0054] The internal solid layer 104 preferably contains a material that conducts ions involved in oxidation-reduction reactions. The ions conducted by this substance are reversible, as described above, such as metal chlorides and insertion materials. The appropriate material should be selected depending on the type of compound that undergoes the redox reaction. For example, the inner solid layer If 104 includes an insertion material, then insertion into and removal from the insertion material It is preferable that the material contains a substance that conducts metal ions.

[0055] Examples of materials that conduct metal ions include ion-conducting ceramics. Therefore, in a preferred embodiment, the internal solid layer 104 is made of insertion material and The insertion material contains an ion-conducting ceramic that conducts metal ions that are inserted into and removed from it. Contains camphor.

[0056] Examples of ion-conducting ceramics include potassium ion-conducting ceramics and sodium Lithium ion conductive ceramics, lithium ion conductive ceramics, calcium conductive Examples include ionic ceramics and magnesium conductive ceramics. Lamix is ​​preferably made of potassium ion conductive ceramics, or sodium ion conductive ceramics. It is a conductive ceramic, and more preferably a sodium ion conductive ceramic.

[0057] More specifically, ion-conducting ceramics include, for example, β'' alumina and β-alumina Acids such as na, perovskite-type oxides, NASICON-type oxides, and garnet-type oxides Examples include hydrocarbon-based solid electrolytes, sulfide-based solid electrolytes, stabilized zirconia, and ion exchangers. It can be used. Furthermore, as an ion exchanger, any substance that exhibits an ion exchange phenomenon is not particularly limited. For example, zeolites (zeolites contain potassium ions such as Na ions, K ions, and H ions inside) Examples include ions, ions, and ion exchange resins, etc. Among these, As ion-conducting ceramics, β" alumina, β-alumina, and zeolites are preferred. Furthermore, β-alumina and β-alumina are more preferred. Such ion-conducting ceramics Camphor wood tends to be highly stable in water.

[0058] β" alumina, and β alumina, have a layered structure consisting of an ion-conducting layer and a spinel block. It contains a structure that allows metal ions to be conducted within the ion-conducting layer. β'' alumina and β'' alumina bond. They differ in their crystal structure, and of these, β'' alumina has sodium in its crystal structure. It has a high um ion content and high ionic conductivity. β" alumina and β alumina are Preferably, Na-β'' alumina and Na-β alumina that conduct sodium ions. Yes. The chemical compositions of Na-β'' alumina and Na-β alumina are typically N, respectively. These are a2O·xAl2O3 (x=5~7) and Na2O·xAl2O3 (x=9~11).

[0059] Materials that conduct metal ions, such as ion-conducting ceramics, have internal properties regardless of their shape. The solid layer 104 may contain the particles, but it is preferable that the particles are contained within it. The shape is not particularly limited and may be, for example, scaly, columnar, spherical, or ellipsoidal. .

[0060] The above-mentioned ion-conducting ceramics and their shapes can be used individually or in combination of two or more types. They can be used together.

[0061] A material that conducts metal ions, such as ion-conducting ceramics, has a solid interior in the form of particles. If included in layer 104, the average particle size of the particles is reversibly such as in insertion material. It is preferable that the particle size be adjusted according to the average particle size of the compounds that undergo the redox reaction. For example, let's explain using ion-conducting ceramics and insertion materials as examples. It is preferable that the average particle size of the conductive ceramics is smaller than the average particle size of the insertion material. Specifically, the ion-conducting ceramics relative to the average particle size of the insertion material The average particle size (= average particle size of ion-conducting ceramics / average particle size of insertion material) is For example, 0.001 to 0.7, preferably 0.005 to 0.6, more preferably The range is 0.01 to 0.3. The above ratio is 0.1 or less, or 0.01, within the above range. It may be 0.5 or less. The average particle size of the ion-conducting ceramics is the insertion material. Because it is smaller than the average particle size and the ratio of the two is within the above range, insertion The oxidation-reduction reaction in the material tends to occur more stably, and the reference electrode 100 is more stable. It tends to show a certain electrode potential.

[0062] The above average particle sizes are specifically 0.02-7 μm, 0.05-5 μm, and 0.1-3 μm. Alternatively, it may be 0.15 to 1 μm. The above average particle size is 0.5 μm within the above range. The average particle size may be less than or equal to m. Note that the above average particle size is measured using a laser diffraction / scattering particle size distribution analyzer. It can be measured by this method.

[0063] The content of materials that conduct metal ions, such as ion-conducting ceramics, is the internal solid layer. For a total mass of 104, the amount is, for example, 15 to 70 parts by mass, preferably 20 It is approximately 65 parts by mass, and more preferably 25 to 60 parts by mass.

[0064] Insertion material in the internal solid layer 104 (a compound that undergoes a reversible oxidation-reduction reaction) ) and the mass of ion-conducting ceramics (materials that conduct ions involved in oxidation-reduction reactions) The ratio (insertion material: ion-conducting ceramics) is, for example, 5:1 to 1:5. Preferably 2:1 to 1:2, and more preferably 1.5:1.0 to 1.0:1.5. Yes, more preferably 1.2:1.0 to 1.0:1.2, and even more preferably The ratio is 1.1:1.0 to 1.0:1.1. Because the above mass ratio is within the above range. The redox reaction in the insertion material tends to occur more stably, and the reference electrode A value of 100 tends to show a more stable electrode potential.

[0065] The internal solid layer 104 preferably contains a conductive agent. The conductive agent is as long as it is conductive. While not particularly limited, examples include carbon black, acetylene black, and Ketjenblack. Carbon nanotubes, graphene, carbon powder, fluorinated carbon, and graphene Carbon materials such as thread powder; conductive fibers such as metal fibers; metal powders such as aluminum Conductive whiskers such as zinc oxide and potassium titanate; conductive materials such as titanium oxide Metal oxides; and organic conductive materials such as phenylene derivatives and graphene derivatives. These can be used. Among these, carbon materials are preferably used.

[0066] The conductive agents and their shapes described above may be used individually or in combination of two or more types. The conductive agent content is, for example, 0.1 to 100 parts by mass of the total mass of the internal solid layer 104. The amount is 20 parts by mass, preferably 1 to 15 parts by mass, and more preferably 2 to 10 parts by mass. be.

[0067] Insertion material in the internal solid layer 104 (a compound that undergoes a reversible oxidation-reduction reaction) The mass ratio of the material to the conductive agent (insertion material: conductive agent) is, for example, 20:1 to 1:1. Preferably, the ratio is 15:1 to 3:1, and more preferably 10:1 to 6:1.

[0068] The internal solid layer 104 is formed to more firmly bond each of the above-mentioned components. It is preferable to include a binder. This makes the reference electrode 100 more stable. It tends to exhibit polar potential.

[0069] As a binder, it is sufficient to bind each component contained in the inner solid layer 104. While not particularly limited, examples include polyvinylidene fluoride, polyvinylpyrrolidone, and polyt Trafluoroethylene, polyethylene, polypropylene, aramid resin, polyamide, por Liimide, polyamideimide, polyacrylonitrile, polyacrylic acid, polyacrylic acid Methyl ester, ethyl polyacrylate, hexyl polyacrylate, Rimethacrylic acid, polymethyl methacrylate, polyethyl methacrylate, Polyhexyl methacrylate, acrylic emulsion, polyvinyl acetate, polyvinyl Lupyrrolidone, polyether, polyethersulfone, hexafluoropolypropylene, Polymers such as styrene-butadiene rubber and carboxymethylcellulose, and these polymers Similar compounds obtained by introducing a modified group into the polymer, and furthermore, copolymers consisting of the above multiple polymers. - are listed below. Among these, (a) polyvinylidene fluoride, (b) styrene A mixture containing lenbutadiene latex and carboxymethylcellulose, (c) A mixture containing riamide, polyimide, and carbodiimide, (d) polytetrafluor (e)ethylene or acrylic emulsion is used, more preferably polyfluoride Nylidene is used.

[0070] The above-mentioned binders may be used individually or in combination of two or more types. The binder content is, for example, 0.1 to 100 parts by mass of the total mass of the internal solid layer 104. The amount is 20 parts by mass, preferably 1 to 15 parts by mass, and more preferably 2 to 10 parts by mass. be.

[0071] Insertion material in the internal solid layer 104 (a compound that undergoes a reversible oxidation-reduction reaction) The mass ratio of the inserting material to the binder (insertion material:binder) is, for example, 20:1 to 1:1. Preferably, the ratio is 15:1 to 3:1, and more preferably 10:1 to 6:1.

[0072] The internal solid layer 104 may contain components other than those described above. Other components include: Examples include MnCO3, Na2CO3, and Al2O3.

[0073] Insertion material (a compound that undergoes a reversible oxidation-reduction reaction) in the internal solid layer, Ion-conducting ceramics (substances that conduct ions involved in oxidation-reduction reactions), conductive agents, and The total amount of binder is, for example, 7 parts by mass of the total mass of the internal solid layer 104. The amount is 0 to 100 parts by mass, preferably 80 to 100 parts by mass, more preferably 90 to The amount is 100 parts by mass, more preferably 95 to 100 parts by mass, and even more preferably This is 99-100 parts by mass.

[0074] In Figure 1, the internal solid layer 104 is shown as a single layer, but the internal solid layer 104 is, It may be a single-layer structure consisting of a single composition, or it may consist of two or more layers having different compositions. It may also include a multilayer structure.

[0075] The average thickness of the internal solid layer 104 is, for example, 1 to 200 μm, preferably 1 to 100 The size is μm, more preferably 1 to 50 μm, and even more preferably 1 to 20 μm. When the internal solid layer 104 has a thickness within the above range, a reference electrode exhibiting a stable electrode potential is obtained. It tends to be possible to manufacture with high manufacturing efficiency and low manufacturing costs.

[0076] (Ionic liquid-containing membrane) The ionic liquid-containing film 106 is located on the internal solid layer 104. In this configuration, the ionic liquid-containing film 106 covers the upper and side surfaces of the internal solid layer 104. When using the light electrode 100, the internal solid layer 104 is configured not to come into direct contact with the sample solution. It has been done.

[0077] The ionic liquid-containing membrane 106 is a membrane-like component containing an ionic liquid, and is gel-like or semi-solid. It is in solid form. The ionic liquid-containing membrane 106 contains an ionic liquid. An ionic liquid is a normal It is a salt that is in a molten (liquid) state at temperature and is composed of cations and anions. Since the ionic liquid-containing film 106 is in contact with the hydrophilic film 108, the ionic liquid-containing film 106 The ionic liquids included are hydrophilic film 108 and ionic liquids, depending on the solubility of the ionic liquids in water. It is distributed to each of the containing membranes 106. Because the ionic liquid has low solubility in water, the hydrophilic membrane At the interface between 108 and the ionic liquid-containing film 106, the concentration of the ionic liquid quickly becomes constant, reaching equilibrium. This state is reached. As a result, the interlibrary potential difference can be suppressed compared to conventional reference electrodes. .

[0078] Ionic liquids are not particularly limited as long as they are salts that are in a liquid state at room temperature. From the viewpoint of reducing the proportion distributed to the ionic membrane 108, the ionic liquid is a hydrophobic ionic liquid. It is preferable to do so. Examples of cations in ionic liquids include imidazolium cations and pyridinium cations. Cation, piperidinium cation, pyrrolidinium cation, quaternary ammonium catio Examples include phosphonium cations or alzonium cations, among which imidazoly Um cations and phosphonium cations are preferred. As anions in ionic liquids, [R 1 SO2NSO2R 2 ] - (R 1 and R 2 That Each independently contains a perfluoroalkyl group having 1 to 5 carbon atoms, fluorine, and tetravalent boron. Borate ion, bis(2-ethylhexyl) sulfosuccinate, AlCl4 - , Al3 Cl7 - NO3 - BF4 - PF6 - CH3COO - CF3COO - CF3SO3 - , (CF3 SO2)2N - , (CF3SO2)3C - AsF6 - SbF6 - F(HF)n -, CF3CF2C F2CF2SO3 - , (CF3CF2SO2)2N - , and CF3CF2CF2COO - Examples include Among them, [R 1 SO2NSO2R 2 ] - (R 1 and R 2 Each of these is independently a part with 1 to 5 carbon atoms. A fluoroalkyl group is preferred. Ionic liquids include, for example, at least one of the above cations and at least one of the above anions. It is a liquid containing one of the above ionic liquids. The above ionic liquids can be used individually or in combination of two or more types. It may be used in this way.

[0079] The ionic liquid-containing membrane 106 is preferably a gel membrane containing an ionic liquid. In one embodiment, the ionic liquid is held by a polymer that is cross-linked in a network-like manner, forming a gel-like membrane. It is formed.

[0080] The polymers that the ionic liquid-containing film 106 may contain are not particularly limited, but for example, f vinylidene-hexafluoropropylene copolymer, polymethyl methacrylate, poly Ethyl methacrylate, polyacrylonitrile, polybutyl acrylate, polyvinyl phosphate Lysine, organic electrolyte oligomers (such as those with a PICPM structure in the main chain cation portion), Examples include polyvinyl chloride and other synthetic rubbers. The polymer is crosslinked with a crosslinking agent. This is often done, for example, a crosslinking agent having multiple fluoroalkylated sulfonylamide groups. It may be bridged by [a certain method]. The above polymers and crosslinking agents may be used individually or in combination of two or more.

[0081] The ionic liquid-containing membrane 106 may contain a plasticizer. If it contains a plasticizer, the ionic liquid The flexibility of the liquid-containing film 106 tends to improve further, and mechanical properties such as tensile strength tend to increase. The properties tend to improve. There are no particular restrictions on the plasticizer, but for example, TEHP (phosphorus) Tris(2-ethylhexyl) acid, NPOE (2-nitrophenyloctyl ether) DOP (dioctyl phthalate), DOS (dioctyl sebacate), DBE (dibasic acid Examples include esters, and BA (butyl acrylate). Plasticizers can be used alone or You may use two or more types in combination.

[0082] The content of each component in the ionic liquid-containing membrane 106 is as follows (per 100 parts by mass of the ionic liquid-containing membrane). In contrast, for example, if the ionic liquid is 1 to 15 parts by mass and the polymer is 15 to 45 parts by mass, The amount of plasticizer may be 50 to 80 parts by mass. Ions per 100 parts by mass of ionic liquid-containing film The liquid content is preferably 1 to 10 parts by mass, and more preferably 1 to 6 parts by mass. The elution of ionic liquid is suppressed because the ionic liquid content is within the above range. It is a tendency.

[0083] The ionic liquid-containing membrane 106 may be a single-layer structure consisting of a single composition, or it may be composed of different compositions. It may also be a multilayer structure comprising two or more layers having the following composition.

[0084] The average thickness of the ionic liquid-containing film 106 is, for example, 1 to 200 μm, preferably 1 to It is 50 μm.

[0085] (hydrophilic membrane) The hydrophilic film 108 is placed on the ionic liquid-containing film 106. Furthermore, the hydrophilic film 108 covers the upper and side surfaces of the ionic liquid-containing film 106.

[0086] Since the hydrophilic membrane 108 is a membrane-like component that has hydrophilic properties, the sample solution penetrates into the membrane. This is possible, and as described above, the ionic liquid is distributed from the ionic liquid-containing membrane 106. It quickly reaches an equilibrium state and exhibits a stable potential. The reference electrode 100 is a hydrophilic film 10 Having 8 makes it less likely for the ionic liquid-containing membrane 106 to come into contact with the biological sample. The effect of various components in the material on the surface state of the ionic liquid-containing film 106 is to be minimized. Yes, it is possible. This allows for the provision of a reference electrode that exhibits a stable electrode potential even when measuring biological samples. It can be provided.

[0087] As shown in the examples described later, the present inventors have developed an ionic liquid-containing membrane that does not have a hydrophilic membrane. When an electrode with exposed electrode potential is immersed in a biological sample and the electrode potential is measured, the biological sample The electrode potential shifts positively compared to when the sample is immersed in a non-conforming sample solution (e.g., a buffer solution). The inventors discovered that one of the causes of this phenomenon is the presence of [something] in the biological sample. We discovered that albumin present in the film is influencing the process, and that hydrophilic membranes are being used on ionic liquid-containing membranes. We found that placing it in this position reduces the effect of the albumin. Therefore, in particular, the reference Because electrode 100 has a hydrophilic membrane 108, the presence or absence of albumin and its concentration can be detected. It can exhibit a stable electrode potential regardless of the circumstances.

[0088] The hydrophilic film 108 is not particularly limited as long as it exhibits hydrophilicity. That is, it does not repel the sample solution. Any form is acceptable as long as it allows penetration. The hydrophilic film 108 is preferably or contain hydrophilic polymers.

[0089] In one embodiment of this present invention, the hydrophilic polymer is selected from the group consisting of polysaccharides and their crosslinked products. It may include at least one selected type. Examples of polysaccharides include pullulan, cellulose, guar gum, xanthan gum, and tamari. Soybean gum, carrageenan, agar, pectin, gum arabic, soybean polysaccharide, acarb - Amylopectin, Inulin, Chitin, Chitosan, β-Glucan, Glycogen, α- Cyclodextrin, β-cyclodextrin, γ-cyclodextrin, stachyose Dextran, dextrin, maltotriose, mannan, merezitose, raffino Examples include cellulose and levan. Among these, pullulan, cellulose, pectin, and levan are particularly noteworthy. Carbose, amylopectin, inulin, chitin, chitosan, beta-glucan, glycogen α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, stak Ox, dextran, dextrin, maltotriose, mannan, meregitose, ra Finose and levan, and their derivatives are preferred, as are cellulose, pullulan, and These derivatives are more preferable.

[0090] As crosslinked polysaccharides, the above-mentioned polysaccharides can be crosslinked with an appropriate crosslinking agent, or by radiation or electron beams. Examples include those that have been cross-linked by irradiation. Furthermore, derivatives of the above polysaccharides include polysaccharides To improve water solubility, the hydroxyl group of the sugar chain is substituted with a substituent.

[0091] To give an example of polysaccharide derivatives using cellulose as an example, cellulose derivatives include hi Promellose (Hydroxypropyl methylcellulose (HPMC)), Promellose phthalate (HPMCP), hypromellose acetate succinate Sterl (HPMCAS), hydroxypropylcellulose (HPC), phthalate acetate Rose (ceracephate), carboxymethyl ethylcellulose (CMEC), ethylcellulose Examples include Lurose and Metrose (registered trademark). Note that Metrose is a cellulose Some of the hydrogen atoms in the hydroxyl group are converted into methyl (-CH3) or hydroxypropyl (-CH2C) groups. Substitution with H(OH)CH3 and / or a hydroxyethyl group (-CH2CH2OH) This derivative has improved water solubility. Therefore, examples of polysaccharide derivatives include hydroxypropylmethyl derivatives and futa. Acetate derivatives, acetate derivatives, succinate derivatives, hydroxypropyl Derivatives such as phthalic acid derivatives, phthalic acid acetate derivatives, carboxymethyl ethyl derivatives, and ethyl derivatives are It can be listed.

[0092] In one embodiment of this design, the hydrophilic polymer is polyvinyl alcohol, polyethylene Oxide, polyvinylpyrrolidone, sodium polyacrylate, polymethacrylate Acrylamide, 2-methacryloyl methacrylate copolymer; acrylamide, 2-methacryloyl methacrylate copolymer; Contains monomer units derived from oxyethyl phosphorylcholine or myristyl alcohol. polymers; and derivatives thereof, and crosslinked products thereof, selected from the group consisting of these polymers and their derivatives. It may contain at least one type.

[0093] Polyvinyl alcohol, polyethylene oxide, polyvinylpyrrolidone, polyacrylic Sodium methacrylate, polymethyl methacrylate, and aminoalkyl methacrylate copolymer -, as well as acrylamide, 2-methacryloyloxyethyl phosphorylcholine, or mi Derivatives of polymers containing monomer units derived from listtyl alcohol include these hydrophilic It is not particularly limited as long as the properties are not impaired, for example, an induction that introduces additional hydrophilic groups. It may be a conductor. Such hydrophilicity is not particularly limited, for example, a hydroxyl group These can be listed. Furthermore, as crosslinked materials, the above-mentioned hydrophilic polymers can be crosslinked with an appropriate crosslinking agent. Examples include materials that have been cross-linked by irradiation with radiation or electron beams.

[0094] Furthermore, hydrophilic polymers are derived from (meth)acrylate and (meth)acrylamide. (Meth)acrylic polymers containing mer units, or allylamine, ethyleneimine, or It may also be an amine polymer containing monomer units derived from oxazoline. Polymers include hydrophobic polymers with a hydrophilic coating on the surface, or hydrophilic polymers with a hydrophilic coating. It may also be a polymer into which the functional group has been introduced. Such a hydrophobic polymer is polystyrene Examples include cellulose, polyethersulfone, etc., and as a hydrophilic coating, cellulose Examples include coatings and polyvinylpyrrolidone coatings.

[0095] As a crosslinking agent used for crosslinking the above hydrophilic polymer, in polyvinyl alcohol These include oxalic acid, boric acid, adipine chloride, glyoxal, thioglycolic acid, polymer Tacryl acid, polyacrylic acid, glutaraldehyde, hexamethylenetetramine, dimethicone Examples include sulfoxides (DMSO), maleic acid, citric acid, and formaldehyde. In polysaccharides (especially carboxymethylcellulose), calcium chloride and ethylene chloride are used. Examples include glycidyl ether (EGDE) and dicarboxylic acid halides. In sodium polyacrylate, divalent or higher metal ions (calcium chloride, and Examples include aluminum hydroxide, etc.; in the case of polymethyl methacrylate, dimethacrylate Ethylene glycol acid is one example. Also, acrylamide is N,N'-methylenebisac acid. Crosslinked polyacrylamide is obtained by polymerization with a crosslinking agent such as acrylic amide. You can obtain this.

[0096] By including the hydrophilic polymer described above, the electrode of the reference electrode 100 during biological sample measurement... It tends to be possible to further stabilize the potential. Also, the above hydrophilic polymers, when used individually, Alternatively, two or more types may be used in combination.

[0097] The hydrophilic film 108 may also include water-soluble hydrophilic polymers among the hydrophilic polymers mentioned above. This is preferable. According to this embodiment, the hydrophilic film 108 gradually dissolves during the measurement of the biological sample. This allows for a constant state in which the surface of the hydrophilic film 108 is not contaminated with components of the biological sample. It is in the direction. Therefore, the reference electrode in this embodiment is even more stable when measuring biological samples. It tends to show a certain electrode potential.

[0098] The hydrophilic film 108 may contain other components in addition to the hydrophilic polymer. The ingredients are not particularly limited, but include, for example, monosaccharides, disaccharides, and other additives. For example, the hydrophilicity of the hydrophilic film 108 is due to the inclusion of these components. It tends to be possible to control the affinity and water solubility.

[0099] Examples of monosaccharides include allose, arabinose, altorose, idose, and erythritol. Thor, erythrulose, erythrose, galactose, galactosamine, xylitol xylose, xylose, glyceraldehyde, glucuronic acid, glucose, glyco Alaldehyde, Grosse, Coritose, Dihydroxyacetone, Dihydroxyacetone sedoheptulose, sorbose, tagatose, talose, 2-deoxy-D-ribose Fucus, fucose, psicose, fructose, mannose, rhamnose, lyxo Examples include ribeye, rib roast, and ribose. Examples of disaccharides include sucrose, cellobiose, turanose, trehalose, and malosaccharides. Chitol, maltose, melibiose, lactulose, lactobionic acid, and lactose These include, and among them, trehalose is preferably used. Other additives include alcohols such as glycerol and its derivatives. .

[0100] The hydrophilic film 108 may be a single layer structure consisting of a single composition, or it may be composed of different compositions. It may be a multilayer structure including two or more layers having, or two or more layers with different compositions repeated Alternatively, it may be a layered structure with randomly stacked layers.

[0101] The average thickness of the hydrophilic film 108 is, for example, 1 μm or more and 1000 μm or less, preferably The particle size is 5 μm or more and 800 μm or less, more preferably 6 μm or more and 400 μm or less. More preferably, the thickness is 8 μm or more and 100 μm or less. The hydrophilic film 108 is 1 μm or more. This allows us to determine the influence of various components in the biological sample on the surface state of the ionic liquid-containing membrane 106. Tends to be able to be made smaller. Also, when the hydrophilic film 108 is 1000 μm or less there is a tendency to be able to make the potential difference caused by the hydrophilic film smaller.

[0102] (Shape) The shape of the reference electrode 100 is not particularly limited and can be any shape such as a cylindrical shape, an elliptical cylindrical shape, and a prismatic shape. Each component included in the reference electrode 100 can be appropriately changed according to the shape of the reference electrode 100.

[0103] (Use) The reference electrode 100 is used as a reference electrode. Specifically, in a sensor or an electrochemical cell, it is used by being electrically connected to a working electrode, and the electrode potential of the working electrode is specified based on the electrode potential of the reference electrode 100. The reference electrode 100 is preferably used for disposable applications. In such applications, the hydrophilic film 108 preferably contains at least one water-soluble polymer selected from the group consisting of polysaccharides and their derivatives. The reference electrode 100 is preferably a reference electrode for calibration free.

[0104] (Manufacturing method) The reference electrode 100 can be manufactured, for example, by forming an internal solid layer 104 on an internal electrode 102, and then sequentially forming an ionic liquid-containing film 106 and a hydrophilic film 108 thereon. Or, an ionic liquid-containing film 106 and a hydrophilic film 108 can be sequentially formed on the internal solid layer 104, and finally the internal electrode 102 can be joined to one end of the internal solid layer 104 for manufacturing. Or, after molding an ionic liquid-containing film 106 on the internal solid layer 104, a separately prepared hydrophilic film 108 can be pressure-bonded onto the ionic liquid-containing film 106 for manufacturing. ​​​​​​​​​​

[0105] The method for forming the internal solid layer is not particularly limited. For example, a composition obtained by mixing each of the above components and, if necessary, a suitable solvent such as 1 -methyl-2-pyrrolidone can be formed into a film on an insulator (or on an internal electrode formed on an insulator) and dried to produce it. Examples of the method for forming a film of the mixture of each component include electrostatic coating, coating with a dispenser, screen printing, sputtering, vapor deposition, and hot pressing, etc., and preferably electrostatic coating.

[0106] The method for forming the ionic liquid-containing film is, for example, a method in which a composition obtained by mixing an ionic liquid, the above-mentioned components such as a polymer and a plasticizer, and, if necessary, a suitable solvent such as tetrahydrofuran is formed into a film on the internal solid layer and dried. The hydrophilic film can be produced, for example, by directly dropping, coating, or spraying a composition obtained by mixing a hydrophilic polymer as described above and a solvent such as water or alcohol onto the ionic liquid-containing film and drying. Alternatively, after forming the composition on a suitable substrate and drying to produce a hydrophilic film, the obtained hydrophilic film can be pressure-bonded onto the ionic liquid-containing film of the reference electrode.

[0107] When crosslinking the hydrophilic polymer, radiation or electron beam irradiation can be performed after forming the hydrophilic film, or a crosslinking agent can be further added to the composition containing the above-mentioned hydrophilic polymer.

[0108] When producing a multilayer-structured hydrophilic film, for example, a method of repeating the steps of dropping, coating, or spraying a composition obtained by mixing a hydrophilic polymer and a solvent and drying can be mentioned.

[0109] Here, a first layer containing a hydrophilic polymer is formed on the ionic liquid-containing film, and then the first When forming a second layer containing another hydrophilic polymer on the first layer, the polymer used when forming the first layer It is preferable that the solvent used and the solvent used to form the second layer are different solvents. According to such a method, when forming the second layer, a composition containing a hydrophilic polymer and a solvent is used for the first layer. When dropped onto the layer, the redissolution of the hydrophilic polymer in the first layer is suppressed, and A multilayer structure containing hydrophilic polymers can be obtained. More specifically, for example, a hydrophilic polymer is formed on an ionic liquid-containing film using water as the solvent. A first layer is formed containing the high hydrophilicity contained in the first layer using an alcohol as a solvent. A second layer containing a hydrophilic polymer other than the molecule may be formed. In this method, the first layer Alcohol is used as the solvent when forming the first layer, and water is used as the solvent when forming the second layer. It may also be used. Furthermore, different hydrophilic polymers may be included by alternately using water and alcohol as solvents. A hydrophilic film with a layered structure may be fabricated by repeatedly forming layers.

[0110] (modified version) The above reference electrode 100 comprises an internal solid layer, an ionic liquid-containing film, and a hydrophilic film. Various modifications are possible. Figure 2 shows a modified example of the reference electrode 100.

[0111] The reference electrode 150, whose schematic cross-sectional view is shown in Figure 2(A), is different from the reference electrode 100. The aqueous film 108 covers only the upper portion of the ionic liquid-containing film 106, and covers the side portion. They differ in that they do not have the same feature. In the reference electrode 150, the side surface of the ionic liquid-containing film 106 is the coating member 1 It is covered by 52.

[0112] The covering member 152 is, for example, a member having insulating properties, and is a member in which the ionic liquid in the ionic liquid-containing film 106 does not infiltrate and does not react with the ionic liquid. The covering member 152 may have a role of fixing the ionic liquid-containing film 106 and the hydrophilic film 108. The ionic liquid does not infiltrate, and is a member that does not react with the ionic liquid. The covering member 152 may have a role of fixing the ionic liquid-containing film 106 and the hydrophilic film 108. The covering member 152 may have a role of fixing the ionic liquid-containing film 106 and the hydrophilic film 108.

[0113] The covering member 152 is not particularly limited, and examples thereof include sealing materials usually used in the manufacture of electrodes, and tapes such as insulating tapes. The covering member 152 is not particularly limited, and examples thereof include sealing materials usually used in the manufacture of electrodes, and tapes such as insulating tapes.

[0114] The reference electrode 170 shown in the schematic cross-sectional view in Fig. 2(B) is different from the reference electrode 150 in that the covering member is separable into a first covering member 172 that covers the side portion of the ionic liquid-containing film 106 and a second covering member 174 that covers the side portion of the hydrophilic film 108. The covering members 172 and 174 may be members made of the same material as the covering member 152. The reference electrode 170 shown in the schematic cross-sectional view in Fig. 2(B) is different from the reference electrode 150 in that the covering member is separable into a first covering member 172 that covers the side portion of the ionic liquid-containing film 106 and a second covering member 174 that covers the side portion of the hydrophilic film 108. The covering members 172 and 174 may be members made of the same material as the covering member 152. The reference electrode 170 shown in the schematic cross-sectional view in Fig. 2(B) is different from the reference electrode 150 in that the covering member is separable into a first covering member 172 that covers the side portion of the ionic liquid-containing film 106 and a second covering member 174 that covers the side portion of the hydrophilic film 108. The covering members 172 and 174 may be members made of the same material as the covering member 152. The covering members 172 and 174 may be members made of the same material as the covering member 152.

[0115] Since the reference electrode 170 is configured such that the covering member is separable as described above, only the hydrophilic film 108 and the covering member 174 can be exchanged. Therefore, according to this aspect, only the hydrophilic film portion can be exchanged for each measurement, and the components other than the hydrophilic film portion can be repeatedly used for measurement while avoiding contamination of the sample. Since the reference electrode 170 is configured such that the covering member is separable as described above, only the hydrophilic film 108 and the covering member 174 can be exchanged. Therefore, according to this aspect, only the hydrophilic film portion can be exchanged for each measurement, and the components other than the hydrophilic film portion can be repeatedly used for measurement while avoiding contamination of the sample. Since the reference electrode 170 is configured such that the covering member is separable as described above, only the hydrophilic film 108 and the covering member 174 can be exchanged. Therefore, according to this aspect, only the hydrophilic film portion can be exchanged for each measurement, and the components other than the hydrophilic film portion can be repeatedly used for measurement while avoiding contamination of the sample. Since the reference electrode 170 is configured such that the covering member is separable as described above, only the hydrophilic film 108 and the covering member 174 can be exchanged. Therefore, according to this aspect, only the hydrophilic film portion can be exchanged for each measurement, and the components other than the hydrophilic film portion can be repeatedly used for measurement while avoiding contamination of the sample.

[0116] [Second Embodiment: Internal Liquid Type Reference Electrode] Fig. 3 is a schematic cross-sectional view of another embodiment of the reference electrode of the present invention. As shown in Fig. 3, the reference electrode 200 of this embodiment includes an internal electrode 202, an internal liquid 206 in which the internal electrode is immersed, and a container 204 that houses the internal electrode 202 and the internal liquid 206. The container 204 has a liquid junction portion 208. In the liquid junction portion 208, the internal liquid 206 and a sample not shown in Fig. 3 Fig. 3 is a schematic cross-sectional view of another embodiment of the reference electrode of the present invention. As shown in Fig. 3, the reference electrode 200 of this embodiment includes an internal electrode 202, an internal liquid 206 in which the internal electrode is immersed, and a container 204 that houses the internal electrode 202 and the internal liquid 206. The container 204 has a liquid junction portion 208. In the liquid junction portion 208, the internal liquid 206 and a sample not shown in Fig. 3 Fig. 3 is a schematic cross-sectional view of another embodiment of the reference electrode of the present invention. As shown in Fig. 3, the reference electrode 200 of this embodiment includes an internal electrode 202, an internal liquid 206 in which the internal electrode is immersed, and a container 204 that houses the internal electrode 202 and the internal liquid 206. The container 204 has a liquid junction portion 208. In the liquid junction portion 208, the internal liquid 206 and a sample not shown in Fig. 3 Fig. 3 is a schematic cross-sectional view of another embodiment of the reference electrode of the present invention. As shown in Fig. 3, the reference electrode 200 of this embodiment includes an internal electrode 202, an internal liquid 206 in which the internal electrode is immersed, and a container 204 that houses the internal electrode 202 and the internal liquid 206. The container 204 has a liquid junction portion 208. In the liquid junction portion 208, the internal liquid 206 and a sample not shown in Fig. 3 An ionic liquid-containing membrane 210 is positioned to isolate the solution, and on the ionic liquid-containing membrane 210 A hydrophilic film 212 is positioned on the sample solution side. The reference electrode 200 has an electrolyte inside the electrode. This is an internal liquid-type reference electrode having [a specific feature / feature].

[0117] Because the reference electrode 200 has the above configuration, it is particularly important for the ionic liquid-containing film 210 and hydrophilicity. Because it has a membrane 212, it exhibits a stable electrode potential even when measuring biological samples. The configuration will be described in detail, but any information that overlaps with the description of the reference electrode 100 will be omitted.

[0118] The reference electrode 200 has an electrode potential determined by a redox reaction on the internal electrode 202. In addition to the compound on the internal electrode 202, the ion in the internal solution 206 is also involved in this oxidation-reduction reaction. It may involve a compound or other substance.

[0119] The reference electrode 200 may be, for example, a silver-silver chloride reference electrode, or a mercury-mercury sulfate reference electrode. Alternatively, a calomel electrode may be used, but a silver-silver chloride electrode is preferred. Therefore, internal Electrode 202 is preferably a silver-silver chloride electrode. In Figure 3, the internal electrode 202 is 1 Although shown as one component, a portion of the lead electrode is coated with a compound such as silver-silver chloride. The electrodes may be treated in a manner that the lead electrodes do not react with silver and chloride ions. It is an electrode.

[0120] The internal solution 206 should be selected appropriately depending on the type of internal electrode 202. For example, internal electrode If 202 is a silver-silver chloride electrode, then the internal solution 206 is a sodium chloride aqueous solution or a sodium chloride solution. This is an aqueous solution containing chloride ions, such as a potassium chloride aqueous solution, and preferably a potassium chloride aqueous solution. More preferably, it is a saturated potassium chloride aqueous solution.

[0121] The containment body 204 is limited in that it can accommodate the internal electrode 202 and the internal liquid 206. Not specified. The containment 204 is, for example, a glass container or polytetrafluoroethylene The molded article may be made of a resin having chemical resistance.

[0122] The liquid junction 208 is formed in the housing 204 and electrically connects the internal liquid 206 and the sample solution. This is the part for connecting to the liquid junction 208. In any case, as long as it performs such a function, This may be an embodiment, but for example, a part made of a porous material such as glass or ceramics. It can be minutes.

[0123] The ionic liquid-containing membrane 210 separates the internal liquid from the sample solution at the liquid junction 208. It is arranged in this manner. Because the ionic liquid-containing membrane 210 is arranged in this way, The internal solution 206 is configured not to come into direct contact with the sample solution when using the reference electrode 200. It is being done.

[0124] The ionic liquid-containing membrane 210 is similar to the ionic liquid-containing membrane 106 in the reference electrode 100. The configuration may be such that the reference electrode 200 includes such an ionic liquid-containing film. Therefore, the liquid potential difference between the inside of the reference electrode 200 (i.e., the internal solution 206) and the sample solution fluctuates. This is suppressed. Furthermore, the leakage of components from the internal liquid 206 into the sample solution is also suppressed.

[0125] The ionic liquid-containing membrane 210 covers the outside of the containment 204, thereby separating the internal liquid from the sample solution. It may be isolated, or it may be filled in the porous portion of the liquid junction 208 so that it can be tested against the internal liquid. The solution may be kept separate.

[0126] The hydrophilic film 212 is located on the sample solution side of the ionic liquid-containing film 210. At electrode 200, the hydrophilic film 212 is in contact with the containment 204 of the ionic liquid-containing film 210. It covers the parts that are not present. In other words, the hydrophilic film 212 covers the ionic liquid-containing film 210. It is arranged in such a way. The hydrophilic film 212 is the hydrophilic film 1 on the reference electrode 100. It may have a configuration similar to that of 08. The reference electrode 200 may have such a hydrophilic film. As a result, the ionic liquid-containing membrane 210 is less likely to come into contact with the biological sample, and various components in the biological sample are less likely to come into contact with the biological sample. This reduces the influence of the minutes on the surface state of the ionic liquid-containing film 210. This makes it possible to provide a reference electrode that exhibits a stable electrode potential even when measuring biological samples. Cut.

[0127] The reference electrode 200 of this embodiment comprises an internal electrode, a housing having a liquid junction, an internal liquid, and an ionic liquid. Various deformations are possible as long as the body-containing membrane and hydrophilic membrane are present. Position of the liquid junction The number and configuration are not limited to those shown in Figure 3 and described above, and may be changed as appropriate.

[0128] In this embodiment, the reference electrode 200 is integrated with a working electrode such as a pH meter, forming a composite electrode. It's fine if they've achieved it.

[0129] The reference electrode 200, for example, has an ionic liquid-containing film formed at the liquid junction of a commercially available internal liquid-type reference electrode. The process can be completed by forming the material and then coating it with a hydrophilic film. (Contains ionic liquid) The method for forming the film and the hydrophilic film is as described in detail in the description of the reference electrode 100.

[0130] The above description of the reference electrode of this embodiment has been given using specific embodiments, but the above implementation The above embodiments are illustrative and can be modified as appropriate. The reference electrode according to the present invention is A If it includes an ionic liquid-containing film and a hydrophilic film disposed on the ionic liquid-containing film, then it is particularly Not limited to this.

[0131] [Third Embodiment: Electrode for Albumin Measurement] Another aspect of this embodiment involves an electrode for detecting or measuring albumin in a sample solution. Yes. Figure 4 is a schematic cross-sectional view of one embodiment of the albumin measurement electrode in this embodiment. As shown, the albumin measurement electrode 300 comprises an internal electrode 302 and a portion located on the internal electrode 302. An internal solid layer 304 is placed there, and an ionic liquid containing an ionic liquid is placed on the internal solid layer 304. It comprises a film 306.

[0132] The albumin measurement electrode 300 is used to detect or measure albumin in a sample solution. This is an electrode for use. The albumin measurement electrode 300 is used in connection with a reference electrode, and the reference electrode The electrode potential is measured using the electrode potential of the following as a reference.

[0133] As described above and in detail in the examples below, the present inventors have developed an ionic liquid-containing membrane We found that the electrode potential of an electrode equipped with [a specific feature] fluctuates depending on the albumin concentration in the sample being measured. The reason is not entirely clear, but if albumin is present in the sample being measured, The distribution state of cations and anions of the ionic liquid in the ionic liquid-containing film to the measurement sample changes. This is thought to be because of the presence of albu in the vicinity of the ionic liquid-containing membrane. As the ion concentration increases, anions become more easily distributed in the sample being measured, or cations become more easily distributed. It is presumed that it will become difficult to distribute into the sample. The principle is not limited to the factors mentioned above.

[0134] Conventionally, electrodes using antibodies, which are used as electrodes for albumin measurement, use antibodies because While manufacturing costs tend to be high, the albumin measurement electrode 300 is suitable for such antibodies and anti- Aptamers that mimic the structure of the body, molecularly imprinted polymers, or albumin-labeled dyes, etc. Since it does not need to contain [a specific ingredient], manufacturing costs can be kept low. Also, albumin measurement Electrode 300 does not respond to gamma globulin, which is the second most abundant substance in the blood after albumin. This allows for the specific detection of albumin in the blood.

[0135] The internal electrode 302, the internal solid layer 304, and the ionic liquid-containing film 306 are, respectively, reference The internal electrode 102, the internal solid layer 104, and the ionic liquid-containing film 106 in electrode 100 The same configuration is also found in the preferred embodiment. The manufacturing method may be appropriately based on the manufacturing method of the reference electrode 100. Internal electrode 302, internal solid The method for forming layer 304 and the ionic liquid-containing film 306 is to use an internal electrode 102 and an internal solid layer 10 4. The method for forming the ionic liquid-containing film 106 may be the same as described above.

[0136] The albumin measurement electrode 300 of this embodiment is immersed in or in contact with the sample to be measured. Various modifications are possible as long as a liquid-containing membrane is present. For example, commercially available ion selectors By replacing the sensitive membrane of the electrode with the above-mentioned ionic liquid-containing membrane, albumin measurement can be performed. A fixed electrode can be obtained.

[0137] The albumin measurement electrode 300 detects albumin in the sample solution, and the sample solution It is used to measure the concentration of albumin in a liquid, etc. The sample solution is preferably a biological sample. It is a material, and more preferably, serum.

[0138] In this embodiment, the albumin measurement electrode described above is used to measure the albumin in the sample solution. The present invention also provides a method for detecting or measuring albumin concentration in the sample to be measured. The albumin measurement electrode of this embodiment and a suitable reference electrode are immersed in the solution, and the potential difference between the two electrodes is measured. This includes the step of taking measurements.

[0139] [Fourth Embodiment: Sensor] Another embodiment of this design is a sensor comprising two electrodes. Figure 5 shows the present design. (A) A schematic plan view and (B) A schematic cross-sectional view along the line X-X' show one embodiment of the sensor. As shown in Figure 5, the sensor 400 is an insulating substrate 402 and is placed on the insulating substrate 402. It comprises a first electrode 410 and a second electrode 420.

[0140] The sensor 400 measures the electrode potential at the second electrode 420 with respect to the first electrode 410. Measurement is taken. That is, in the sensor 400, the first electrode 410 is the reference electrode, and the second Electrode 420 is the working electrode.

[0141] The first electrode 410 consists of an internal electrode 418 and an internal solid electrode located on the internal electrode 418. Layer 412, an ionic liquid-containing film 414 disposed on the internal solid layer 412, and ionic liquid It comprises a hydrophilic film 416 disposed on a body-containing film 414. The first electrode 410 is above The reference electrodes 100, 150, or 170 described above may be used. That is, internal electrode 418, internal The solid layer 412, the ionic liquid-containing film 414, and the hydrophilic film 416 are each connected to the reference electrode 1 Internal electrode 102, internal solid layer 104, ionic liquid-containing film 106, and hydrophilicity in 00 The film may have the same configuration as film 108, and the preferred embodiment is also the same. Therefore, the first The electrode 410 exhibits a stable electrode potential even when measuring biological samples.

[0142] The second electrode 420 consists of an internal electrode 428 and an internal solid electrode located on the internal electrode 428. It comprises a layer 422 and an ion-selective film 423 disposed on the internal solid layer 422. The part electrode 428 and the internal solid layer 422 are, respectively, the internal electrode 1 of the reference electrode 100. 02 may have the same configuration as the internal solid layer 104, and the preferred embodiment is also the same. .

[0143] The components contained in the internal solid layer 422 are preferably changed as appropriate depending on the ions being measured. For example, the internal solid layer 422 is an insertion material for the measurement ion and transmits the measurement ion. It is preferable that it contains a fermentable substance.

[0144] In the sensor 400, internal electrodes 418 and 428, and internal solid layer 412 It is preferable that the internal solid layer 422 is substantially identical. Such a sensor can be manufactured in fewer steps. Because it can be manufactured, the manufacturing cost becomes even lower. Also, during measurement, internal solid Even if the interfacial potential between the body layer and the electrode changes over time, the internal electrode and the internal solid layer remain the same as the first electrode. If the electrode and the second electrode are substantially identical, the change in the interfacial potential is the same between the first electrode and the second electrode. Since they are almost equal at the poles, the electrode potential at the second electrode is measured with respect to the first electrode. When measuring, the change in the interface potential cancels out, resulting in a more stable measurement over time. They tend to be able to determine the outcome. Furthermore, the statement that two internal electrodes are substantially identical means that two internal electrodes are substantially the same pair This means that it is composed of materials that have the properties of [the material]. Also, the two internal solid layers are substantial Being identical means that the two internal solid layers have substantially the same composition.

[0145] (Ion-selective membrane) The second electrode 420 is equipped with an ion-selective membrane 423, so that the measurement ions in the sample solution The electrode potential changes depending on the concentration. The first electrode 410 remains constant regardless of the concentration of the ion being measured. To indicate the electrode potential, the electrode potential of the second electrode 420 is measured using the first electrode 410 as a reference. By doing so, the concentration of the measured ion can be quantified.

[0146] In the second electrode 420, the ion-selective film 423 is located on the upper and side surfaces of the internal solid layer 422. It is coated, and configured so that the internal solid layer 422 does not come into direct contact with the sample solution.

[0147] The ion-selective membrane 423 contains an ion-selective substance. An ion-selective substance is a predetermined substance. It is a substance that can recognize only certain ions and incorporate them into an ion-selective membrane. The material should be selected appropriately depending on the application of the sensor 400.

[0148] Examples of ion-selective materials include conventionally known ionophores and synthetic materials. Preferably, an ionophore is used. Examples of ionophores include valinomycin and monet. Syn, rhodopsin, nonactin, monactin, ionomycin, gramicidin A, nidi Erisin, CCCP (carbonyl cyanide-m-chlorophenylhydrazone), and FC Examples include CP (carbonyl cyanide-p-trifluoromethoxyphenylhydrazone). Furthermore, synthetic materials include crown ethers and acyclic nonylphenoxypolymers. Examples include Tanol, etc. More specifically, DD16C5, Bis-12Crown-4 , 12-Crown-4, 15-Crown-5, 18-Crown-6, and Kalec Examples include suarenes. The above ion-selective substances can be used individually or in combination of two or more. They can be used together.

[0149] The ion-selective film 423 preferably contains a binder resin in addition to the ion-selective substance. The binder resin is not particularly limited, but for example, polyvinyl chloride, polyvinyl chloride Vinylidene, polyacrylonitrile, polyurethane, polyvinyl acetate, silicone elastomer Mer, polyvinyl alcohol, cellulose ester, polycarbonate, vinyl chloride / vinegar Vinyl chloride copolymer, vinyl chloride / vinyl acetate / vinyl alcohol copolymer, and vinyl chloride Examples include polyvinylidene chloride copolymers. The components of the above binder resin can be used individually. Alternatively, two or more types may be used in combination.

[0150] The ion-selective membrane 423 preferably further contains a plasticizer. The flexibility of the ion-selective film 423 tends to improve further, for example, in terms of tensile strength. Mechanical properties tend to improve. As a plasticizer, the ionic liquid-containing film 106 may contain plasticizers. You may use an agent.

[0151] The ion-selective membrane 423 preferably further contains an anion elimination agent. The agent can be appropriately selected depending on the ion being measured. Examples of anion exclusion agents include, for example... Sodium tetrakis(4-chlorophenyl)borate (Na-TCPB), tetrakis( 4-chlorophenyl)potassium borate (K-TCPB), tetrakis[3,5-bis(t Sodium (Na-TFPB) phenyl (difluoromethyl)borate, tetrakis[3, 5-Bis(trifluoromethyl)phenyl]potassium borate (K-TFPB), tetraf Potassium phenylborate (K-TPB), sodium tetraphenylborate (Na-TPB) ), and tetrakis[3,5-bis(1,1,1,3,3,3-hexafluoro-2-methyl Examples of tetraphenylborate salts include sodium toxy-2-propyl)phenyl]borate. The above anion eliminators can be used individually or in combination of two or more types. stomach.

[0152] The content of each component in the ion-selective membrane 423 is 10 times the total mass of the ion-selective membrane 423. For example, with 0 parts by mass, the ion-selective substance is 1 to 10 parts by mass, and the binder resin is 1 The composition is 5 to 45 parts by mass, with 50 to 80 parts by mass of plasticizer and 0.1 to 5 parts by mass of anion eliminator. This is the mass part.

[0153] The ion-selective membrane 423 may be a single-layer structure consisting of a single composition, or it may be composed of different compositions. It may also be a multilayer structure comprising two or more layers having the same composition.

[0154] The average thickness of the ion-selective film 423 is, for example, 30 to 300 μm.

[0155] (Insulating substrate) The insulating substrate 402 has the role of holding the first electrode 410 and the second electrode 420. The insulating substrate 402 has insulating properties and electrically connects the first electrode 410 and the second electrode 420. The substrate is not particularly limited as long as it is not a continuous substrate. The insulating substrate is, for example, polyvinyl alcohol. Polyethylene terephthalate, polybutylene terephthalate, polyethylene naphthalate , and polyester resins such as polybutylene naphthalate, polyimide, epoxy resin, The substrate may include glass, ceramics, metal oxides, and fibrous materials such as paper. .

[0156] (Application) Sensor 400 can detect various ions by appropriately changing the type of ion-selective membrane 423. It can be used as a sensor. Sensor 400 is, for example, a sodium sensor or potassium It may be a mu. Furthermore, the sensor 400 is suitably used as a sensor for measuring biological samples. It is also suitable for disposable use. The sensor 400 is preferably a calibrated It is a shock-free sensor.

[0157] Figure 6 shows an example of how to use the sensor 400. As shown in Figure 6, the insulating base The first electrode 410 and the second electrode 420 are immersed on the plate 402, and the measurement sample 44 Add 0 as a drop. The sample to be measured may be a biological sample. First electrode 410 and second electrode 4 With 20 in contact with the sample to be measured, the potentiometer 43 connected to the internal electrodes 418 and 428 By reading the potential difference between the two electrodes using 0, the concentration of the ion to be measured in the sample can be determined. It is possible. Alternatively, in another embodiment, the sensor of this embodiment is located between the first electrode and the second electrode. It may also be used to measure the current flowing through it.

[0158] Sensor 400 is used as described above, thus stabilizing the potential in ion measurement. From this perspective, the distance (shortest distance) between the first electrode 410 and the second electrode 420 is, for example, 2 mm or less. It is preferable that it be above. From a similar viewpoint, the spacing is more preferably 3 mm or more, and further Preferably 4 mm or more, more preferably 5 mm or more. The upper limit of this interval is It is possible to simultaneously contact a small amount of the same sample with both the ion-selective electrode and the reference electrode. From that perspective, for example, these could be 20mm, 15mm, 10mm, 8mm, or 6mm.

[0159] (Manufacturing method) The sensor 400 has a first electrode 410 and a second electrode 420 formed on an insulating substrate 402. The first electrode 410 can be manufactured by using the reference electrode of this embodiment. The manufacturing method should be referred to as appropriate. Specifically, on the insulating substrate 402, the internal electrodes 418 A layer is formed on the internal electrode 418, consisting of an internal solid layer 412, an ionic liquid-containing film 414, and a hydrophilic layer. The sex membrane 416 can be formed sequentially.

[0160] A method for manufacturing the second electrode 420 involves, for example, forming an internal electrode 428 on an insulating substrate 402. If an internal solid layer 422 and an ion-selective film 423 are sequentially formed on the internal electrode 428, Good. The formation of the internal electrode 428 and the internal solid layer 422 is used to manufacture the reference electrode of this embodiment. The same method should be used. Furthermore, the ion-selective membrane 423 can be made of, for example, an ion-selective substance. The above-mentioned components, such as binder resin, plasticizer, and anion eliminator, and acetone as needed. A composition obtained by mixing it with a suitable solvent is formed as a film on an internal solid layer and dried. It should be the law.

[0161] (modified version) The sensor 400 of this embodiment is equipped with two electrodes, one of which is used as the reference electrode. The electrode on the other side consists of an ionic liquid-containing membrane and a hydrophilic membrane placed on the ionic liquid-containing membrane. As long as the necessary components are available, various transformations are possible.

[0162] For example, the first electrode 410 is not limited to the solid-type reference electrode described above, but may also be the reference electrode 20 described above. An internal liquid type reference electrode like 0 may also be used. Furthermore, the first electrode 410 is the reference electrode 10 A reference electrode with values ​​of 0, 150, 170, or 200 may be used, with appropriate modifications.

[0163] Furthermore, the second electrode 420 does not necessarily have to be equipped with an ion-selective membrane. Instead, the electrode potential of the second electrode is changed according to the concentration of the compound or ion in the sample being measured. It may have a component that can do so. For example, in sensor 400, the second electrode is the first This electrode has an ionic liquid-containing membrane 306 instead of the ion-selective membrane 423 of electrode 2. In this embodiment, the second electrode is an albumin measurement electrode 300.

[0164] In an embodiment in which the second electrode is an albumin measurement electrode 300, internal electrode, internal solid layer Furthermore, it is preferable that the ionic liquid-containing membrane is substantially identical between the first electrode and the second electrode. These sensors can be manufactured with fewer steps, thus further reducing manufacturing costs. Furthermore, during measurement, the interface potential between the internal solid layer and the electrode, and / or the internal solid layer Even if the interfacial potential of the ionic liquid-containing film changes over time, the internal electrode, internal solid layer and If the on-liquid-containing film is substantially the same at the first electrode and the second electrode, the change in the interfacial potential is... Since the chemical reaction is almost equal between the first and second electrodes, the second electrode is used as the reference point with respect to the first electrode. When measuring the electrode potential at the electrode, the change in the interfacial potential cancels out. This tends to allow for more stable measurements over time.

[0165] Furthermore, in the sensor 400, a plurality of second electrodes are arranged on the insulating substrate 402. The plurality of second electrodes may be the same, and according to this embodiment, multiple electrodes can be used at once. Because it can measure, it can be made into a more accurate sensor. Alternatively, the multiple The two electrodes may be different, and according to this embodiment, measurements of multiple components can be performed at once. For example, the sensor 400 has one first electrode which is a reference electrode and multiple It may also include a second electrode. Here, the multiple second electrodes are ion-selective electrodes and The device may include an albumin measurement electrode 300, and as an ion-selective electrode, sodium At least one of the following ion-selective electrodes, potassium ion-selective electrodes, and chloride ion-selective electrodes It may also include one type.

[0166] The above description of this embodiment has been made using specific embodiments, but the above embodiments are illustrative examples. Yes, and the above embodiments can be modified as appropriate. For example, in the above embodiments, This includes preferred, more preferred, even more preferred, and even more preferred embodiments, etc. The embodiments described therein may be combined in any way. For example, in the sensor of this embodiment, The first electrode is the reference electrode of this embodiment, and the second electrode is for albumin measurement of this embodiment. In an embodiment where the electrode is a reference electrode, preferred, more preferred, even more preferred, or The following are preferred embodiments, and preferred, more preferred, and even more preferred embodiments of the electrode for albumin measurement. This specification may be used in any combination of the above or any more preferred embodiment. The numerical range described is obtained by arbitrarily combining the upper and lower limits. Good. For example, a lower limit or upper limit of a preferred range and a lower limit or upper limit of a more preferred range. You may also select a numerical range by combining these in any way you like. [Examples]

[0167] The present invention will be described in more detail below using examples and comparative examples. This is not limited in any way by the examples provided.

[0168] [Example 1: Performance study of an electrode having an ionic liquid-containing membrane] (Electrode fabrication) An internal electrode, an internal solid layer placed on the internal electrode, and a solid layer placed on the internal solid layer An electrode as shown in Figure 4, having an ionic liquid-containing membrane, was fabricated.

[0169] First, the insertion material (Na 0.33 MnO2 (orthogonal crystal structure, average grain size 8.9μ m, scaly)), ion-conducting ceramics (β” alumina:Na2Al 10.6 O 15.9 , (Average particle size 0.26 μm), conductive agent (acetylene black), and binder (polyvinyl fluoride) (Redene) Insertion material: Ion conductive ceramics: Conductive agent: Binding agent = 8:8 Add and mix the methyl-2-pyrrolidone in a 1:1 composition ratio to the solvent (1-methyl-2-pyrrolidone) to form a slurry. Prepared. The prepared slurry is transferred onto a platinum electrode on an insulating substrate (alumina substrate) by electrostatic force. After the material is applied to the target by electrostatic coating and then layered, the solvent is completely removed in a vacuum drying oven. By doing so, an internal solid layer was formed on the internal electrode.

[0170] Next, an ionic liquid ([TBMOEP + ][C1C1N - ]: Tributyl (2-methoxyethyl)phosphonium bis(trifluoromethanesulfonyl)imide) 4 parts by mass, plasticizer (tris(2-ethylhexyl phosphate)) 64 parts by mass, and polymer (poly A tetrahydrofuran solution containing 32 parts by mass of vinyl chloride is applied and dried. From this, an electrode A having an internal solid layer and an ionic liquid-containing film was obtained. The average total thickness of the body-containing membranes was 60 μm.

[0171] (Measurement of albumin and gamma globulin solutions) The electrode potential of electrode A was measured using the measurement system shown in Figure 7, while changing the sample being measured. This includes electrode A, shown as electrode 504, and silver-silver chloride reference electrode 508 (saturated KCl, double Junction NaCl 140mM (mmol·dm -3 )) and via potentiometer 510 Connect the electrodes and ensure that the measurement sample 506 is immersed in electrode A and the silver-silver chloride reference electrode. 506 was dropped onto the insulating substrate 502. The open-circuit potential of electrode A relative to the silver-silver chloride reference electrode was The measurement was taken for 3 minutes.

[0172] The sample used for measurement is albumin (bovine serum albumin), which is a major serum protein. This uses a 140 mM NaCl solution containing γ-globulin (human plasma-derived γ-globulin). It contained albumin or gamma globulin, and a solution containing albumin or gamma globulin. Measure both 140 mM NaCl solutions containing albumin or γ-globulin. Measurement potential E of a solution and measurement potential E of a solution that does not contain albumin or γ-globulin. base and The difference (ΔE=EE base The following was calculated by changing the concentration of albumin or γ-globulin. Multiple ΔE values ​​were measured. The results are shown in Figure 8. From Figure 8, it can be seen that albumin is present in the sample being measured. It was found that a potential shift occurs only in this case.

[0173] Therefore, two electrodes A were prepared, and the albumin concentration (2-10g) was measured for the two samples. The relationship between ( / dL) and potential shift ΔE was investigated. The results are shown in Figure 9. From Figure 9, it can be seen that the reproducibility was high. It was found that a potential shift at electrode A occurs depending on the albumin concentration.

[0174] Therefore, electrode B was further modified by changing the type and content of the ionic liquid in the ionic liquid-containing membrane. Prepare electrodes C and D, and use standard serum (JCTCM 130-4 M) for each electrode. The potential shift ΔE was measured in standard serum. The concentrations of the substance were 4.37 mM, 140.4 mM, 105.1 mM, and 3.1 g, respectively. The value is / dL, and the potential shift ΔE is the measurement result E for a 140 mM NaCl solution. base Based on It was calculated as follows. Electrodes B and C shall have ionic liquid content of 10% by mass and 20% by mass, respectively. Electrode D was prepared in the same manner as electrode A, except for the following: Electrode D was prepared using [TBMOE] as the ionic liquid. P + ][C2C2N - ](Tributyl(2-methoxyethyl)phosphonium bis(trifluoro Other than using roethanesulfonyl imide and having an ionic liquid content of 20% by mass It was prepared in the same manner as electrode A.

[0175] The results are shown in Figure 10. From Figure 10, it can be seen that even when the content and type of ionic liquid are changed, the potential shift remains the same. It was found that a problem occurs.

[0176] Based on the above, electrodes having an ionic liquid-containing membrane are useful as electrodes for albumin measurement. It was found that... Furthermore, in the measurement of biological samples containing albumin, ionic liquids... When a membrane-covered electrode is used as a reference electrode, the electrode voltage changes depending on the albumin concentration in the biological sample. This suggests that the position may change.

[0177] [Example 2: Performance evaluation of a solid-state reference electrode having a hydrophilic film] Next, suppressing the potential shift caused by albumin in electrodes with an ionic liquid-containing membrane. We considered the methods.

[0178] (Electrode fabrication) First, in the same manner as electrode A, an internal solid layer and an ionic liquid-containing film are formed on the internal electrode. An electrode was fabricated. Next, the electrode was treated with methylose SH (manufactured by Shin-Etsu Chemical Co., Ltd.). A solution containing 2% by mass of product name and 10% by mass of trehalose is dropped onto an ionic liquid-containing membrane. By drying, a water-soluble hydrophilic film is formed on the ionic liquid-containing film of electrode E. As shown in Figure 1, the electrode E has a hydrophilic film covering the sides of the ionic liquid-containing film. The average thickness of the hydrophilic film was 9 μm.

[0179] Electrodes F and G were prepared in the same manner as electrode E, except that a hydrophilic film was formed using the methods described below. Electrodes G, H, and I were prepared. Note that electrodes G to I are located on the side of the ionic liquid-containing membrane as shown in Figure 1. The surface was also covered with a hydrophilic film, and the average thickness of the hydrophilic film was 9 μm. Electrode F: Electron beam crosslinked polyvinyl alcohol hydrate as described in Japanese Patent Publication No. 5572016 A draggel membrane (containing 268 mM KCl, average thickness 700 μm) is pressed onto an ionic liquid-containing membrane. Then, as shown in Figure 2, the gel was secured with tape. Electrode G: 2% by mass of Metrose SH (manufactured by Shin-Etsu Chemical Co., Ltd., product name) and 30% by mass of trehalose. An aqueous solution containing a certain percentage of the substance was dropped onto an ionic liquid-containing film and dried. Electrode H: 2% by mass of metholose SH (manufactured by Shin-Etsu Chemical Co., Ltd., product name) and 10% by mass of xylose An aqueous solution containing % was dropped onto an ionic liquid-containing film and dried. Electrode I: 2% by mass of Metroze SM (manufactured by Shin-Etsu Chemical Co., Ltd., product name) and 10% of trehalose An aqueous solution containing a certain percentage of the substance was dropped onto an ionic liquid-containing film and dried. Electrode J: An aqueous solution containing 10% by mass of pullulan is dropped onto a suitable substrate and dried to form a flat surface. A pullulan film with a uniform thickness of 350 μm was fabricated. The pullulan film was pressed onto an ionic liquid-containing film, as shown in Figure. As shown in 2, the pullulan membrane was secured around the edges with tape.

[0180] (Measurement of potential shift) Using the same measurement system as in Example 1, as shown in Figure 7, the measurement potential E of the albumin solution was measured using electrode E. And, the measurement potential E of the buffer solution that does not contain albumin. base The difference (ΔE=EE) base ) calculate The albumin solution contained a buffer solution (K10 buffer) with 10 g / dL albumin. Using this method, the buffer solution (K10 buffer) consists of 10 mM potassium ions and 140 mM A phosphate buffer solution containing sodium ions and 1.5 mM phosphate ions was used.

[0181] The specific protocol is as follows: First, apply the albumin-containing solution to electrode E. The solution was dropped and the potential was measured for 3 minutes. Afterwards, electrode E was thoroughly washed with the above buffer solution to remove the hydrophilicity. The membrane was dissolved and completely removed. Next, a fresh buffer solution was added to the electrode and left for 3 minutes. The potential was measured. Then, using this electrode, the potential of the buffer solution and the albumin-containing solution were measured in sequence. The procedure was finalized. Before each measurement, the electrodes were washed with buffer solution. The measurement protocol and results are shown below. As shown in 1.

[0182] [Table 1]

[0183] Table 1 shows that if the electrode has a hydrophilic film, the potential shift caused by albumin is suppressed. This was suggested. To verify the suppression of potential shift by the hydrophilic film, see Tables 2 and 3. The verification measurements shown were performed. In the measurements shown in Table 2, a hydrophilic film was not formed. Measurements were performed using the electrode (i.e., electrode A). Furthermore, in the measurements shown in Table 3... Next, we investigated the effect of the presence or absence of a hydrophilic film on the measurement potential. The results are shown in Tables 2 and 3.

[0184] [Table 2]

[0185] [Table 3]

[0186] From the results shown in Tables 1-3, in electrodes having an ionic liquid-containing membrane, the ionic liquid-containing membrane It was confirmed that placing a hydrophilic membrane on top suppresses the potential shift caused by albumin. Therefore, electrodes containing an ionic liquid-containing membrane and a hydrophilic membrane are used when measuring biological samples. It was found that it can be used as a reference electrode that exhibits a stable electrode potential.

[0187] Next, the potential shift was measured using electrodes A and F-J instead of electrode E. As an example, the potential shift was measured using a silver-silver chloride reference electrode instead of electrode E. .

[0188] The specific protocol is as follows: First, apply an albumin-containing solution to each electrode. The solution was dropped onto the electrode, and the potential was measured for 3 minutes. Afterwards, the electrode was thoroughly washed with buffer solution (K1 buffer). Then, the hydrophilic membrane was dissolved and completely removed. The buffer solution (K1 buffer) was 1 mM potassium ions, 140 mM sodium ions, and 1.5 mM phosphate ions A phosphate buffer solution containing [the specified substance] was used. At electrode F, the hydrophilic film that was pressed was physically removed. After that, cleaning was performed. Next, only cleaning was performed on the silver-silver chloride reference electrode. Next, a new buffer solution was dropped onto this electrode, and the potential was measured for 3 minutes. The sample to be measured was: The buffer solution and buffer solution contained 10 g / dL albumin, similar to the above. For pole J only, the measurement time for the potential was set to 10 minutes.

[0189] Figure 11 shows the potential shift ΔE in the measurement of each electrode. Electrodes F to J, which have a hydrophilic film on top, are comparable to the silver-silver chloride reference electrode shown as an example. It showed a potential shift of ΔE of a degree or small. On the other hand, only electrode A, which does not have a hydrophilic film, showed a large potential shift. The potential shift ΔE was shown.

[0190] From the above, the ionic liquid-containing membrane and the hydrophilic membrane placed on the ionic liquid-containing membrane An electrode equipped with these features is preferred as a reference electrode that exhibits a stable electrode potential even when measuring biological samples. It was found that it could be used appropriately.

[0191] [Example 3: Performance evaluation of ion sensor] Next, the ionic liquid-containing membrane and the hydrophilic membrane disposed on the ionic liquid-containing membrane are provided. The performance of an ion sensor with electrodes was investigated.

[0192] (Fabrication of ion sensors) A sensor, as shown in Figure 5, comprises a potassium ion selective electrode and a reference electrode on an insulating substrate. A sensor was prepared. As an example, a sensor using the above electrode J as a reference electrode was compared with a comparative example. Then, two samples of sensors were fabricated using electrode A as the reference electrode.

[0193] The potassium ion selective electrode was prepared as follows: in the same manner as electrode A described above. Next, an internal solid layer was formed on top of the platinum electrode, which is the internal electrode. Then, on top of the internal solid layer, Onophore (Valinomycin) 3 parts by mass, Plasticizer (Tris(2-ethylhexyl phosphate) ) 67.9 parts by mass, anion eliminator (potassium tetrakis(4-chlorophenyl)borate) Tetra containing 0.3 parts by mass of ) and 28.8 parts by mass of binder resin (polyvinyl chloride) By applying a hydrofuran solution and drying it, the internal solid layer is coated with potassium iodide. A potassium ion-selective membrane was fabricated. The average thickness of the potassium ion-selective electrode was 60 μm.

[0194] (Measurement of standard serum) The performance of the potassium ion sensors in the examples and comparative examples was evaluated using the measurement system shown in Figure 12. Specifically, a first electrode (reference electrode) 610 and a second electrode (potassium) are placed on an insulating substrate 602. A sensor (potassium ion sensor) 600 equipped with a um ion selective electrode 620 measures Sample 640 was dropped. The first electrode (reference electrode) 610 and the second electrode were connected via the potentiometer 630. The electrode (potassium ion selective electrode) 620 is connected, and the second electrode (potassium ion On-selective electrode) 620 and silver-silver chloride reference electrode 608 (saturated) immersed in the measurement sample 640 KCl, double junction NaCl 140mM (mmol·dm -3 )) and the potential difference The connection was established via a total of 632 connections.

[0195] The specific protocol is as follows: First, standard serum is used as the measurement sample 640. Drop JCTCM 130-4 M) onto the electrode, with the first electrode (reference electrode) 610 as the reference electrode. The electrode potential E of electrode 2 (potassium ion selective electrode) 620 was measured, and silver-chloride The electrode electrode of the second electrode (potassium ion selective electrode) 620 is based on the silver reference electrode 608. position E ref The measurement was taken for 3 minutes. Next, the sensor was washed with the above buffer solution (K1 buffer). Afterward, the same measurement was performed on the buffer solution (K1 buffer), and the first electrode (reference electrode) was measured. ) Electrode potential E of the second electrode (potassium ion selective electrode) 620, with 610 as the reference. base and a second electrode (potassium ion selective electrode) 6 based on the silver-silver chloride reference electrode 608. Electrode potential E of 20 ref_base The potential difference (ΔE=EE) was then measured. base and ΔE ref =E ref -E ref_base The following values ​​were calculated: Note that in standard serum, K, Na, Cl, and A The lubumin concentrations were 4.37 mM, 140.4 mM, 105.1 mM, and 3 mM, respectively. The level was 0.1 g / dL.

[0196] The above measurements were performed on the sensors of the two fabricated embodiments and the sensors of the two comparative examples. For both the sensor in the example and the sensor in the comparative example, the average value of the potential difference ΔE was calculated. Also, the potential difference ΔE for a total of four sensors. ref The average value was calculated. Sensor of the example The average value of the potential difference ΔE in each of the comparative sensor, and for a total of four sensors ΔE ref The average values ​​are shown in Figure 13.

[0197] In the sensor of the embodiment using a reference electrode that has not only an ionic liquid-containing membrane but also a hydrophilic membrane, The results are comparable to those of reference examples using silver-silver chloride reference electrodes, which are commonly used in conventional clinical measurements. The following measurement results were obtained. On the other hand, in the comparative example sensor using a reference electrode without a hydrophilic film, The measurement results differed significantly from those of the reference sensor. Therefore, the ionic liquid-containing The sensor equipped with the reference electrode of this embodiment, which has a hydrophilic film on a film, is used when measuring a biological sample. This suggests that it provides a stable potential even when in a stable state.

[0198] [Example 4: Measurement of biological samples using an albumin sensor] (Fabrication of albumin sensor) Three sensor samples were fabricated, each equipped with an albumin measurement electrode and a reference electrode on an insulating substrate. Electrodes A and J were fabricated adjacent to each other on the alumina substrate in the same manner as described above.

[0199] (Creating a calibration curve) Using the fabricated sensor, the potential E of a phosphate buffer solution containing albumin was measured. Next... Then, after washing the sensor with phosphate buffer, the same measurement was performed with phosphate buffer, and then... position E base The potential difference ΔE (ΔE = EE) was measured. base The value was calculated. We changed the albumin concentration of the sample and performed a total of three measurements, and examined the relationship between albumin concentration and potential difference ΔE. A calibration curve was created by plotting the coordinates. The created calibration curve is shown in Figure 14. This result Therefore, an electrode equipped with an ionic liquid-containing membrane is used as the working electrode, and the ionic liquid-containing membrane and the hydrophilic membrane are The fact that the electrode provided can be used as a reference electrode in a sensor can be used as an albumin sensor. Understood.

[0200] [Example 5: Measurement of biological samples using a pH sensor] The hydrophilic film is not only used in solid-type electrodes that have an ionic liquid-containing film, but also in solid-type electrodes that have an ionic liquid-containing film. We will also verify that the potential shift caused by albumin is suppressed in the internal liquid-type electrodes that are equipped with this system. To do this, a pH meter equipped with a commercially available internal-liquid type reference electrode is used to measure the albumin-containing solution. Measurements were taken.

[0201] (Preparation and construction of pH meter) As a comparative example, a silver-silver chloride reference electrode with an ionic liquid-containing film placed at the liquid junction and glass A commercially available pH meter equipped with a pH electrode (PUREIL, Horiba, Ltd., product name) Preparations were made. In addition, on the ionic liquid-containing film in the liquid junction of the pH meter, the same as electrode F was applied. The polyvinyl alcohol hydrogel film prepared in this way was pressed and then secured with tape. A pH meter was then fabricated according to the example. Additionally, as reference example 1, a pH meter having an ionic liquid-containing membrane was fabricated. A commercially available pH meter equipped with a silver-silver chloride reference electrode and a glass pH electrode was prepared. As an example 2, consider a commercially available pH meter equipped with a silver-silver chloride reference electrode and a glass membrane pH electrode. I'm ready.

[0202] (Measuring the pH of albumin solution) Using the pH meters prepared as described above for the Examples, Comparative Examples, Reference Example 1, and Reference Example 2 Then, albumin is added to a buffer solution with a pH of 7.4 at various concentrations (3 g / dL, 6 g / dL, or The solutions were measured after adding 10 g / dL of the solution. The measurement method was as described in the instructions for each pH meter. I referred to the manual. The results are shown in Figure 15.

[0203] From Figure 15, the reference electrode of the comparative example in which an ionic liquid-containing membrane is placed at the liquid junction is albumin The measurement results vary significantly depending on the concentration, and the correct pH is not being measured due to the influence of albumin. This suggests that it has not been achieved. On the other hand, the implementation in which a hydrophilic film is placed on an ionic liquid-containing film The pH meter in the example, as well as the pH meters in Reference Examples 1 and 2 that do not have an ionic liquid-containing membrane, are It exhibits a pH of approximately 6.8 regardless of lubumin concentration, and the hydrophilic membrane contains an ionic liquid-containing membrane. In addition to solid-type electrodes, internal liquid-type electrodes equipped with an ionic liquid-containing membrane also have an ionic liquid-containing membrane. This suggests that it suppresses the potential shift caused by lubumin.

[0204] [Example 6: Electrode having a multilayer hydrophilic film] Except for forming a hydrophilic film using the methods described below, electrode K and electrodes K and L were prepared. The average thickness of the hydrophilic film in electrodes K and L was approximately 10 μm and It was approximately 20 μm. Electrode K: An aqueous solution containing 10% by mass of pullulan and 3% by mass of glycerol is used to form an ionic liquid-containing membrane. It was then dripped onto the surface and allowed to dry. In addition, 5 mass of Metroze SH (manufactured by Shin-Etsu Chemical Co., Ltd., product name) was added. An 80% by mass ethanol solution containing % and 1.5% by mass glycerol is dropped onto a pullulan membrane. And then it was dried. Electrode L: An aqueous solution containing 10% by mass of pullulan and 3% by mass of glycerol is used to form an ionic liquid-containing membrane. It was then dripped onto the surface and allowed to dry. In addition, 5 mass of Metroze SH (manufactured by Shin-Etsu Chemical Co., Ltd., product name) was added. An 80% by mass ethanol solution containing % and 1.5% by mass glycerol is dropped onto a pullulan membrane. It was then dried. Furthermore, an aqueous solution containing 10% by mass of pullulan and 3% by mass of glycerol was prepared. The methazole solution was dropped onto a methazole film and dried.

[0205] Electrodes K and L mentioned above are also electrodes in which the potential shift due to albumin is suppressed, similar to electrodes E to J. It is an electrode and is suitable for use as a reference electrode that exhibits a stable electrode potential even when measuring biological samples. It is possible to be there. [Explanation of symbols]

[0206] 100,150,170,200...Reference electrode, 102,202,302,418,42 8...Internal electrode, 104,304,412,422...Internal solid layer, 106,210,306 ,414…Ionic liquid-containing membrane, 108,212,416…Hydrophilic membrane, 152,172,1 74...Coating member, 204...Container, 206...Internal liquid, 208...Liquid junction, 300...Album Measuring electrodes, 400, 600... Sensors, 402, 502, 602... Insulating substrates, 410, 610...First electrode, 420,620...Second electrode, 423...Ion-selective membrane, 430, 510, 630, 632…Potentiometer, 440, 506, 640…Measurement sample, 504…Electrode , 508, 608... Silver-silver chloride reference electrodes.

Claims

1. An electrode for detecting or measuring albumin in a sample solution, comprising an ionic liquid-containing membrane.

2. The electrode according to claim 1, wherein the ionic liquid content in the ionic liquid-containing membrane is 1 to 15 parts by mass per 100 parts by mass of the ionic liquid-containing membrane.

3. The electrode according to claim 1 or 2, wherein the average thickness of the ionic liquid-containing film is 1 μm or more and 200 μm or less.

4. The electrode according to any one of claims 1 to 3, wherein the ionic liquid-containing membrane is a gel membrane containing an ionic liquid.

5. The electrode is a solid-type electrode comprising an internal electrode and an internal solid layer disposed on the internal electrode. The electrode according to any one of claims 1 to 4, wherein the ionic liquid-containing membrane is disposed on the internal solid layer.

6. The electrode according to claim 5, wherein the internal solid layer contains an insertion material and an ion-conducting ceramic.

7. The electrode according to claim 6, wherein the insertion material is a metal oxide, an oxygen redox material, or a Prussian blue analog.

8. The aforementioned metal oxide, M ｘ MnO ２ The electrode according to claim 7, wherein M represents Na or K, and x represents any positive number.

9. The electrode according to any one of claims 6 to 8, wherein the ion-conducting ceramic is β'' alumina or β-alumina.

10. The device comprises an insulating substrate and a first electrode and a second electrode disposed on the insulating substrate, A sensor in which the first electrode comprises an ionic liquid-containing membrane and is an electrode for detecting or measuring albumin in a sample solution.

11. The first electrode and the second electrode are electrodes comprising an internal electrode and an internal solid layer disposed on the internal electrode, In the first electrode, the ionic liquid-containing film is arranged on the internal solid layer. The internal electrode and the internal solid layer are substantially identical in the first electrode and the second electrode. The sensor according to claim 10.

12. The first electrode and the second electrode are electrodes comprising an internal electrode and an internal solid layer disposed on the internal electrode, In the first electrode and the second electrode, the ionic liquid-containing film is arranged on the internal solid layer. The internal electrode, the internal solid layer, and the ionic liquid-containing film are substantially identical in the first electrode and the second electrode. The sensor according to claim 10.

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