Ion sensor, ion quantification method, and ion quantification apparatus

Abstract

We provide ion sensors with excellent physical stability. [Solution] An ion sensor for coulometric titration to quantify target ions contained in a sample, comprising a cathode electrode (11) and a laminate (101), wherein the laminate includes, in this order, a cation-receiving layer (13) containing a first organic phase that accepts cations contained in the sample, a chloride ion-conducting layer (14) containing chloride ions and cations and capable of conducting chloride ions, and an anode electrode (15) that emits anions when it accepts electrons, the ion sensor (10).

Description

[Technical Field]

[0001] This disclosure relates to an ion sensor, an ion quantification method, and an ion quantification apparatus. [Background technology]

[0002] Known methods for measuring the concentration of ions in a sample include coulometric titration, ion chromatography, potentiometric titration, voltammetry, and colorimetric methods. Of these, coulometric titration is a method in which a voltage is applied to the measurement system to allow the phase transfer of the target ion or an electrochemical reaction such as a redox reaction to proceed, and the total amount of current (electrical quantity) that flows through the measurement system until the transfer or reaction stops is determined, and the target ion is quantified based on the electrical quantity. In principle, coulometric titration is easy to perform because the product of the amount of target ion contained in the sample and the valence of the target ion is equal to the electrical quantity, and it does not require the calibration work that is usually required in other measurement methods.

[0003] As an example of technology related to coulometric titration, the ion sensor described in Patent Document 1 is known. Patent Document 1 describes an ion sensor comprising an organic phase holding layer containing an organic phase capable of forming an interface with a sample containing target ions, a first electrode containing a first insertion material composed of an inorganic compound, and a second electrode that comes into contact with the sample. [Prior art documents] [Patent Documents]

[0004] [Patent Document 1] Japanese Patent Publication No. 2023-34205 [Non-patent literature]

[0005] [Non-Patent Document 1] S. Tatsumi, T. Omatsu, K. Maeda et al., "An all-solid-state thin-layer laminated cell for calibration-free coulometric determination of K+", Electrochimica Acta 408 (2022) 139946, doi:10.1016 / j.electacta.2022.139946. [Overview of the project] [Problems that the invention aims to solve]

[0006] In the ion sensor described in Patent Document 1, a powdered insertion material mediates the electric current, requiring a configuration that enhances the adhesion between the insertion material and other layers. The ion sensor described in Patent Document 1 employs a binder and a conductive agent kneaded into the insertion material as such a configuration. However, the binder and conductive agent may peel off or detach from the insertion material due to deformation of the layers of the insertion material caused by oxidation-reduction reactions during ion sensor use, and external forces such as vibrations that occur during ion sensor transport. Therefore, the ion sensor described in Patent Document 1 has a problem with physical stability in which the adhesion of the insertion material decreases under environments subject to deformation and external forces, resulting in decreased electrolytic efficiency and consequently decreased quantitative accuracy.

[0007] One aspect of this disclosure aims to provide an ion sensor with excellent physical stability. [Means for solving the problem]

[0008] To solve the above problems, an ion sensor according to one aspect of the present disclosure is an ion sensor for coulometric titration to quantify a target ion contained in a sample, comprising a cathode electrode and a laminate, the laminate comprising, in this order, a cation-receiving layer containing a first organic phase that receives cations contained in the sample, a chloride ion-conducting layer containing chloride ions and cations and capable of conducting chloride ions, and an anode electrode that emits anions when it receives electrons. [Effects of the Invention]

[0009] According to one aspect of this disclosure, an ion sensor with excellent physical stability is provided. [Brief explanation of the drawing]

[0010] [Figure 1] This is a schematic diagram showing the configuration of an ion quantification device according to Embodiment 1 of this disclosure. [Figure 2] Figure 1 is a schematic diagram showing an example of ion flow in an ion sensor equipped with an ion quantification device. [Figure 3] Figure 1 is a schematic perspective view showing the configuration of the ion sensor in the ion quantification device, with the ion sensor shown in the open position. [Figure 4] Figure 1 is a schematic perspective view showing the configuration of the ion sensor in the ion quantification device shown, and it shows the state after the ion sensor has been manipulated so that the spacer contacts the cation receiving layer, as shown in Figure 3. [Figure 5] Figure 1 is a schematic perspective view showing the configuration of the ion sensor in the ion quantification device shown, and it shows the state after the sample has been introduced, as shown in Figure 4. [Figure 6] Figure 1 is a schematic perspective view showing the configuration of the ion sensor in the ion quantification device shown, and it shows the state after the ion sensor has been operated so that the cathode electrode contacts the spacer, as shown in Figure 5. [Figure 7] Figure 1 shows a flowchart illustrating the flow of an ion quantification method using the ion sensor provided in the ion quantification device. [Figure 8]It is a schematic diagram showing the configuration of an ion quantification device according to a modification of Embodiment 1 of the present disclosure. [Figure 9] It is a schematic diagram showing the configuration of an ion quantification device according to Embodiment 2 of the present disclosure.

MODE FOR CARRYING OUT THE INVENTION

[0011] 〔Embodiment 1〕 Hereinafter, Embodiment 1 of the present disclosure will be described with reference to the drawings. Note that the scope of the present disclosure is not limited to this embodiment and can be arbitrarily changed within the scope of the technical idea of the present disclosure.

[0012] <Sample, and target ions> The form of the sample S may be either liquid or solid. In this embodiment, it is liquid. When a liquid sample S is adopted, the sample S and the ion sensor 10 tend to adhere closely, and it is easy to improve the quantification accuracy of ions. The liquid sample S may be used for coulometric titration as it is in the sampled state, or may be used after being subjected to purification or dilution using water or a buffer or the like.

[0013] In the present disclosure, the type of the sample S is not particularly limited. Examples of the type of the sample S include: biological samples such as blood, urine, saliva, and sweat; medical liquids such as infusion solutions for intravenous drip and artificial dialysis solutions; drinking water such as mineral water and sports drinks. Among them, the sample S is preferably a biological sample. In clinical sites where ion quantification of biological samples is performed, the ion sensor 10 is often used as a disposable item, and therefore the ion sensor 10 also has many opportunities to receive external forces such as vibration during the distribution process. The ion sensor 10 according to the present embodiment has excellent physical stability and is less likely to cause a decrease in electrolysis efficiency even when subjected to external forces, and thus is suitable as an ion sensor for biological samples.

[0014] In this disclosure, the type of target ion is not particularly limited and may be either a cation or anion. Examples of cations include: metal cations such as potassium ions, sodium ions, lithium ions, calcium ions, and magnesium ions; nitrogen-containing cations such as tetraalkylammonium ions, trialkylammonium ions, and guanidinium ions. Examples of anions include: halide ions such as fluoride ions, chloride ions, and bromide ions; inorganic anions such as sulfate ions, nitrate ions, and nitrite ions; and carboxylate ions such as acetate ions, lactate ions, and citrate ions.

[0015] <Ion Quantitative Measuring Device> The ion quantification apparatus 100 according to this embodiment will be described with reference to Figure 1. Figure 1 is a schematic diagram showing the configuration of the ion quantification apparatus 100 according to Embodiment 1 of this disclosure. The ion quantification apparatus 100 is an article for coulometric titration to quantify target ions contained in a sample S.

[0016] As shown in Figure 1, the ion quantification device 100 includes an ion sensor 10, and a voltage application unit 20 and a current measurement unit 30 connected to the cathode electrode 11 and anode electrode 15 of the ion sensor 10.

[0017] The voltage application unit 20 may be a known voltage / current generator, and in this embodiment, it is a DC voltage / current generator. The current measurement unit 30 may be a known current measuring instrument.

[0018] As shown in Figure 1, in this embodiment, the cathode electrode 11, voltage application unit 20, current measurement unit 30, and anode electrode 15 of the ion quantification device 100 are connected via a wire in this path. However, in this disclosure, the connection path is not limited to that shown in Figure 1. In this disclosure, any connection path can be used as long as the current passes through the cathode electrode, the sample S introduced into the ion sensor 10, and the anode electrode in that order, and further through the current measurement unit 30. In other words, in this disclosure, it is sufficient that the voltage application unit 20 and the current measurement unit 30 are electrically connected to the cathode electrode 11 and the anode electrode 15, either directly or indirectly via other components.

[0019] <Ion Sensor> The ion sensor 10 according to this embodiment is an article for coulometric titration to quantify target ions contained in a sample S. As shown in Figure 1, the ion sensor 10 comprises a cathode electrode 11, a spacer 12, and a laminate 101 in that order. The laminate 101 includes a cation receiving layer 13, a chloride ion conducting layer 14, and an anode electrode 15 in that order.

[0020] The ion sensor 10 is not limited to the layer configuration shown in Figure 1. In this disclosure, the ion sensor 10 may further include an insulating plate made of an insulating material on the side of the cathode electrode 11 facing away from the sample chamber SR. Similarly, the ion sensor 10 may further include an insulating plate made of an insulating material on the side of the anode electrode 15 facing away from the sample chamber SR.

[0021] (Cathode electrode) The cathode electrode 11 is located on the upper surface of the ion sensor 10 and is in contact with the sample chamber SR. The cathode electrode 11 functions as a cathode in the current flowing through the ion sensor 10.

[0022] In this embodiment, a thin plate of silver / silver chloride electrode is used as the cathode electrode 11. However, in this disclosure, the material constituting the cathode electrode 11 is not limited to silver / silver chloride, but any material that functions as a cathode is acceptable. Other examples of materials constituting the cathode electrode 11 include various electrode materials modified with redox derivatives, and examples of such various electrode materials include carbon electrodes, carbon paste, platinum, gold, copper, and glass electrodes.

[0023] In this disclosure, it is preferable that the cathode electrode 11 is made of a material capable of fixing anions contained in the sample S to its surface. For example, if the sample S contains chloride ions, using a silver / silver chloride electrode as the cathode electrode 11 is advantageous because silver ions from the cathode electrode 11 combine with chloride ions to form silver chloride, which is fixed to the surface of the cathode electrode 11, thus maintaining a constant potential in the sample.

[0024] (Spacer) Spacer 12 is provided between the cathode electrode 11 and the cation receiving layer 13. Spacer 12 is a component for providing a sample chamber SR between the cathode electrode 11 and the cation receiving layer 13. The sample chamber SR is a space for storing a sample S and is a space that is in contact with the cathode electrode 11 and the cation receiving layer 13.

[0025] In this embodiment, a thin resin plate having through holes 121 that penetrate the spacer 12 in the thickness direction is used as the spacer 12. When the spacer 12 is sandwiched between the cathode electrode 11 and the cation receiving layer 13, a sample chamber SR is formed in which the upper surface abuts the cathode electrode 11, the lower surface abuts the cation receiving layer 13, and the circumferential surface is formed by the through holes 121.

[0026] In this disclosure, the material constituting the spacer 12 is not limited to resin, but may be any insulating material that does not substantially react with the sample S. Another example of a material is glass.

[0027] The volume of the sample chamber SR is determined by the thickness of the spacer 12 and the dimensions of the through-hole 121, and may be adjusted according to the amount of sample S that can be collected. In this embodiment, the volume of the sample chamber SR is 1 μL or more and 10 mL or less, but the disclosure is not limited to this volume.

[0028] (Cation-receiving layer) The cation-receiving layer 13 is provided between the spacer 12 and the chloride ion conductive layer 14 and is in contact with the sample chamber SR. The cation-receiving layer 13 contains a first organic phase that receives cations contained in the sample S.

[0029] The first organic phase has the function of accepting cations contained in the sample S, and its main part is composed of organic compounds. The components of the first organic phase are not particularly limited as long as the first organic phase accepts cations contained in the sample S.

[0030] The first organic phase may contain a first component, which is a non-volatile organic compound with a high dielectric constant. When the first organic phase contains the first component, its cation-receiving function is enhanced, and the solubility of the solute in the first organic phase is improved, thereby reducing solute precipitation and improving the long-term stability of the ion sensor 10. Examples of the first component include plasticizers such as o-nitrophenyl octyl ether (NPOE), dioctyl sebacate (DOS), dioctyl adipate, and dioctylphenyl phosphonate; and high-boiling point compounds such as nitrobenzene.

[0031] When the target ion is a cation, the first organic phase may include a second component that specifically accepts the target ion. When the first organic phase includes such a second component, the cation-accepting layer 13 specifically accepts the target ion, making it possible to selectively quantify the target ion even when multiple types of cations, including the target ion, are present in the sample S. Examples of the second component include ionophores. Examples of ionophores include valinomycin, monesin, rhodopsin, nonactin, monactin, ionomycin, gramicidin A, nigericin, carbonyl cyanide-m-chlorophenylhydrazone (CCCP), carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP), crown ether, nonylphenoxypolyethanol, DD16C5, Bis-12Crown-4, 12-Crown-4, 15-Crown-5, 18-Crown-6, and Carexalene.

[0032] Furthermore, if the cations contained in sample S are poorly soluble in organic compounds, the first organic phase may include an ion exchanger as a third component. When the first organic phase includes an ion exchanger, the function of the cation receiving layer 13 in accepting cations that are poorly soluble in organic compounds is enhanced. Examples of ion exchangers include tetrakis(4-chlorophenyl)borate potassium salt and tetrakis[3,5-bis(trifluoromethyl)phenyl]borate sodium salt.

[0033] The first organic phase may contain a fourth component that improves the mechanical strength of the cation-receiving layer 13. An example of the fourth component is a polymer that is miscible with the sample S. Examples of polymers include: homopolymers such as polyvinyl chloride (PVC), polymethyl methacrylate (PMMA), polyethyl methacrylate, and polystyrene; copolymers composed of two or more monomers such as methyl methacrylate-styrene copolymer, ethylene-styrene copolymer, styrene-ethylene-styrene block copolymer, styrene-ethylene-butylene-styrene block copolymer, and styrene-ethylene-propylene-styrene block copolymer.

[0034] Furthermore, when the first organic phase is used as a liquid, the first organic phase may further contain an organic solvent as a fifth component that dissolves other components. Examples of organic solvents include those insoluble in water, and specific examples include paraffin, dodecyl alcohol, and tetradecyl alcohol.

[0035] The structure of the cation-receiving layer 13 is not particularly limited, as long as it does not severely impair adhesion with other adjacent layers. The cation-receiving layer 13 may contain multiple phases, or it may be composed of a homogeneous system of the first organic phase. Examples of multiple phases contained in the cation-receiving layer 13 include: a combination of a liquid or solid first organic phase and a solid supporting the first organic phase. Examples of solids supporting the first organic phase include porous materials, with specific examples being membrane filters and filter paper. A more specific example of a cation-receiving layer 13 containing multiple phases is a membrane filter impregnated with a liquid first organic phase. Specific examples of a cation-receiving layer 13 composed of a homogeneous system of the first organic phase include: a liquid film made of a liquid first organic phase; and a solid film formed by shaping the first organic phase into a film and drying it.

[0036] In this embodiment, NPOE is used as the first component of the first organic phase, and valinomycin is used as the second component of the first organic phase. The cation receiving layer 13 in this embodiment uses a membrane filter impregnated with NPOE in which valinomycin is dissolved.

[0037] (Chloride ion conductive layer) The chloride ion conductive layer 14 is provided between the chloride ion conductive layer 14 and the anode electrode 15. The chloride ion conductive layer 14 contains chloride ions and cations and is a layer capable of conducting chloride ions. In the ion sensor 10 according to this embodiment, during coulometric titration, an electric current is generated in the ion sensor 10 due to the conduction of cations contained in the sample S and chloride ions contained in the chloride ion conductive layer. In the conventional technology, solid insertion materials were used to generate the current, and these insertion materials were fixed using organic binders. Therefore, in the conventional technology, deformation due to temperature changes and peeling or detachment due to vibration were problems. The chloride ion conductive layer 14 of this embodiment can use a single organic phase or an organic phase filled in a porous body that does not require a binder, and problems such as peeling and detachment are less likely to occur, and it has very high resistance to deformation and vibration. Therefore, compared to conventional technologies that utilize oxidation-reduction reactions rather than ion conduction for current generation, the cation receiving layer 13 and the chloride ion conducting layer 14 tend to exhibit high shape stability and maintain interlayer adhesion even when current is applied to the ion sensor 10. As a result, the ion sensor 10 according to this embodiment has excellent physical stability.

[0038] The chloride ion conductive layer 14 may contain a second organic phase or an aqueous phase as a phase capable of conducting chloride ions. Since the chloride ion conductive layer 14 and the adjacent cation receiving layer 13 contain a first organic phase, it is advantageous for the chloride ion conductive layer 14 to similarly contain a second organic phase, as this simplifies the layer structure of the ion sensor 10 and improves the mass productivity of the ion sensor 10.

[0039] The composition of the second organic phase is not particularly limited, as long as the second organic phase can conduct chloride ions.

[0040] The second organic phase may contain a first component, which is a non-volatile organic compound with a high dielectric constant. When the second organic phase contains the first component, its function in conducting chloride ions is enhanced, and the solubility of the solute in the second organic phase improves, thereby reducing solute precipitation and improving the long-term stability of the ion sensor 10. An example of the first component of the second organic phase is the same as an example of the first component of the first organic phase, and therefore its explanation will not be repeated.

[0041] The second organic phase may include a second component that improves the mechanical strength of the chloride ion conductive layer 14. An example of the second component of the second organic phase is the same as the example of the fourth component of the first organic phase, and therefore its explanation will not be repeated.

[0042] Furthermore, when the second organic phase is used as a liquid, the second organic phase may further contain an organic solvent as a third component that dissolves other components. The example of the third component of the second organic phase is the same as the example of the fifth component of the first organic phase, and therefore the explanation will not be repeated.

[0043] The aqueous phase contained in the chloride ion conductive layer 14 mainly consists of water. The aqueous phase may consist of water, but may also contain other components such as agarose and a viscosity-enhancing agent such as gelatin. The other components are not particularly limited as long as the aqueous phase can conduct chloride ions.

[0044] The chloride ion conductive layer 14 contains cations as counterions to chloride ions. The type of cation contained in the chloride ion conductive layer 14 is not particularly limited. Depending on whether the chloride ion conductive layer 14 contains the second organic phase or the aqueous phase, the cation may be appropriately selected from those that exist in ionic form in the second organic phase or the aqueous phase.

[0045] Among cations, cations that do not readily undergo redox reactions are preferred. As a prior art, Non-Patent Literature 1 is known, which utilizes redox reactions for electric current generation. Non-Patent Literature 1 emphasizes improving electrolytic efficiency and employs the conductive polymer PEDOT-PEG:TFPB as a substance that readily undergoes redox reactions. However, substances that readily undergo redox reactions have a problem with chemical stability, as they readily oxidize in the air regardless of whether electricity is applied, leading to a decrease in electrolytic efficiency. Therefore, in this embodiment, by employing a cation that does not readily undergo redox reactions as the counterion of chloride ions that mediate electric current generation, the chemical stability of the ion sensor is improved, and the decrease in the electrolytic efficiency of the ion sensor due to deterioration over time, such as air oxidation, is slowed.

[0046] When the chloride ion conductive layer 14 contains a second organic phase, the cations contained in the chloride ion conductive layer 14 only need to be oil-soluble and are not particularly limited. An example of a cation is: tetraalkylammonium cation (R4N + ), trialkylammonium cation (R3HN + ), nitrogen-containing cations such as benzyltrialkylammonium cations and guanidinium ions; tetraalkylphosphonium cations (R4P + ), and phosphorus-containing cations such as tetraphenylphosphonium cation; trialkylsulfonium cation (R3S +Examples include sulfur-containing cations such as ) and arsenic-containing cations such as tetraphenylarsonium cations. Here, R represents any alkyl group. As cations that are less likely to undergo redox reactions, it is preferable to select the cation from the group consisting of tetraalkylammonium cations, trialkylammonium cations, and tetraalkylphosphonium cations. Examples of tetraalkylammonium cations include trioctylmethylammonium cation, toridodecylmethylammonium cation, ditetradecyldimethylammonium cation, dihexadecyldimethylammonium cation, dioctadecyldimethylammonium cation, and benzyltrimethylammonium cation. Polymers modified with tetraalkylammonium can also be suitably used as cations in the second organic phase. Specific examples include poly(vinylbenzyltrimethylammonium chloride) and copolymers thereof with styrene, or triblock copolymers thereof with styrene and ethylene. Examples of trialkylammonium cations include trioctylammonium cation and tridecylammonium cation. Examples of tetraalkylphosphonium cations include triethyloctylphosphonium cation, triethyldodecylphosphonium cation, and tributyloctylphosphonium cation.

[0047] When the chloride ion conductive layer 14 contains an aqueous phase, the cations contained in the chloride ion conductive layer 14 are not particularly limited as long as they are water-soluble. Examples of cations include: metal cations such as lithium, sodium, potassium, rubidium, cesium, calcium, and magnesium; and nitrogen-containing cations such as ammonium cations, tetramethylammonium cations, tetraethylammonium cations, and guanidium cations.

[0048] The structure of the chloride ion conductive layer 14 is not particularly limited, as long as the adhesion to other adjacent layers is not severely impaired. The chloride ion conductive layer 14 may contain multiple phases or may consist of a single-phase homogeneous system. Examples of multiple phases contained in the chloride ion conductive layer 14 include: a combination of a liquid or solid second organic phase or a liquid aqueous phase and a solid supporting the second organic phase or aqueous phase. Examples of solids supporting the second organic phase or aqueous phase include porous materials, with specific examples being membrane filters and filter paper. A more specific example of a chloride ion conductive layer 14 containing multiple phases is a membrane filter impregnated with a liquid second organic phase or aqueous phase. Specific examples of a chloride ion conductive layer 14 consisting of a single-phase homogeneous system include: a liquid film consisting of a liquid second organic phase or aqueous phase; and a solid film formed by shaping the second organic phase into a film and drying it.

[0049] In this embodiment, NPOE is used as the first component of the second organic phase, and tetraalkylammonium is used as the cation. In this embodiment, the cation receiving layer 13 is a membrane filter impregnated with NPOE in which a chloride salt of tetraalkylammonium is dissolved.

[0050] (Anode electrode) The anode electrode 15 is located on the underside of the ion sensor 10 and is in contact with the chloride ion conductive layer 14. The anode electrode 15 functions as an anode in the current flowing through the ion sensor 10 and emits anions when it accepts electrons.

[0051] In this embodiment, a thin plate of silver / silver chloride electrode is used as the anode electrode 15. However, in this disclosure, the material constituting the anode electrode 15 is not limited to silver / silver chloride, but is not particularly limited as long as it functions as an anode and emits anions when it accepts electrons. The emitted anions are not particularly limited, but are preferably anions that the chloride ion conductive layer 14 can conduct, and an example of such an anion is chloride ion. Other examples of materials constituting the anode electrode 15 include silver / silver bromide and silver / silver iodide.

[0052] In this embodiment, the anode electrode 15 is a thin plate of silver / silver chloride electrode, just like the cathode electrode 11. Thus, when the anode electrode 15 and the cathode electrode 11 are made of the same material, the mass productivity of the ion sensor 10 is improved.

[0053] (Flow of ions) Regarding the flow of ions in the ion sensor 10 according to this embodiment, it will be described with reference to FIG. 2. FIG. 2 is a schematic diagram showing an example of the flow of ions in the ion sensor 10 included in the ion quantification device 100 shown in FIG. 1. In the example shown in FIG. 2, a sample S containing potassium cations K + and chloride ions Cl - is introduced into the sample chamber SR, and a voltage E app is applied from the cathode electrode 11 toward the anode electrode 15.

[0054] As shown in FIG. 2, at the cathode electrode 11, Ag releases electrons and ionizes into Ag + , and Ag + combines with Cl - contained in the sample S and deposits on the surface of the silver / silver chloride electrode as AgCl. In order to maintain the electrical neutrality of the sample S, valinomycin contained in the cation receiving layer 13 specifically receives K + contained in the sample S. In order to maintain the electrical neutrality of the cation receiving layer 13, chloride ions contained in the chloride ion conductive layer 14 move to the cation receiving layer 13. When the anode electrode 15 receives electrons and Cl− is released to the chloride ion conductive layer 14, the electrical neutrality of the chloride ion conductive layer 14 is maintained.

[0055] (Method of introducing sample) A more detailed structure of the ion sensor 10 and a method of introducing the sample S into the ion sensor 10 will be described with reference to FIGS. 3 to 6.

[0056] Figure 3 is a schematic perspective view showing the configuration of the ion sensor 10 of the ion quantification device 100 shown in Figure 1, and shows the ion sensor 10 in the open state. As shown in Figure 3, the laminate 101 is formed by stacking a chloride ion conductive layer 14 and a cation receiving layer 13 on the anode electrode 15 in that order. The cathode electrode 11, spacer 12 and anode electrode 15 have substantially the same rectangular shape, and one side of each layer is bonded to each other, and each layer can be rotated independently around the bonded portion formed by that side as the central axis. By rotating each layer so that they are separated from each other, the ion sensor 10 opens, and by rotating each layer so that they are in contact with each other, the ion sensor 10 closes. Here, the cathode electrode 11 and the anode electrode 15 are separated by the spacer 12 in each layer including the bonded portion, so even when the ion sensor 10 is closed, the cathode electrode 11 and the anode electrode 15 do not come into direct contact.

[0057] As shown in Figure 3, the cathode electrode 11 has a main portion that contacts other layers when the ion sensor 10 is closed, and a connecting portion 111 that extends in one direction from the main portion. Similarly, the anode electrode 15 also has a main portion that contacts other layers when the ion sensor 10 is closed, and a connecting portion 151 that extends in one direction from the main portion.

[0058] Figure 4 is a schematic perspective view showing the configuration of the ion sensor 10 of the ion quantification device 100 shown in Figure 1, and shows the state after operating the ion sensor 10 so that the spacer 12 contacts the cation receiving layer 13, as shown in Figure 3. As shown in Figure 4, when the spacer 12 is rotated so that it contacts the cation receiving layer 13, the through hole 121 overlaps with the cation receiving layer 13. As a result, a sample chamber SR is formed, with its lower surface in contact with the cation receiving layer 13 and its circumferential surface formed by the through hole 121.

[0059] Figure 5 is a schematic perspective view showing the configuration of the ion sensor 10 of the ion quantification device 100 shown in Figure 1, and shows the state after introducing the sample S from the state shown in Figure 4. As shown in Figure 5, when the liquid sample S is dropped into the sample chamber SR, the sample S is stored in the sample chamber SR.

[0060] Figure 6 is a schematic perspective view showing the configuration of the ion sensor 10 of the ion quantification device 100 shown in Figure 1, and shows the state after operating the ion sensor 10 so that the cathode electrode 11 contacts the spacer 12, from the state shown in Figure 5. As shown in Figure 6, when the cathode electrode 11 is rotated so that it contacts the spacer 12, the upper surface of the sample chamber SR that houses the sample S comes into contact with the cathode electrode 11. As a result, the sample S comes into contact with the cathode electrode 11 and the cation receiving layer 13.

[0061] As shown in Figure 6, the connection portion 111 of the cathode electrode 11 and the connection portion 151 of the anode electrode 15 are arranged so that they extend in the same direction and do not overlap with other layers when the ion sensor 10 is closed. In this embodiment, the connection portion 111 of the cathode electrode 11 is connected to the voltage application unit 20 via a wire. The connection portion 151 of the anode electrode 15 is connected to the current measurement unit 30 via a wire.

[0062] <Method for quantifying ions> The ion quantification method M100 according to this embodiment will be described with reference to Figure 7. Figure 7 is a flowchart showing the flow of the ion quantification method M100 using the ion sensor 10 provided in the ion quantification device 100 shown in Figure 1. The ion quantification method M100 is a method for quantifying target ions using the ion sensor 10.

[0063] As shown in Figure 7, the ion quantification method M100 includes an introduction step S11, a voltage application step S12, and a calculation step S13. Furthermore, the ion quantification method M100 includes a correction step S14 after the calculation step S13.

[0064] (Introduction process) The introduction step S11 is a step in which the sample S is introduced between the cathode electrode 11 and the cation receiving layer 13. In this embodiment, as described above for the method of introducing the sample S, the introduction step S11 is performed by dropping the liquid sample S into the sample chamber SR formed by the through hole 121 of the spacer 12 and closing the ion sensor 10.

[0065] In this disclosure, the procedure for introducing the sample S in the introduction step S11 can be appropriately selected depending on the configuration of the ion sensor 10 and the form of the sample S, as long as the sample S is introduced so that it comes into contact with the cathode electrode 11 and the cation receiving layer 13.

[0066] (Voltage application process) The voltage application step S12 is a step in which a voltage is applied between the cathode electrode 11 and the anode electrode 15, and the current flowing between the cathode electrode 11 and the anode electrode 15 is measured.

[0067] In this embodiment, the ion quantification device 100 is constructed by connecting the connection part 111 of the cathode electrode 11 and the voltage application unit 20, the connection part 151 of the anode electrode 15 and the current measurement unit 30, and the voltage application unit 20 and the current measurement unit 30, respectively, via conductors. Next, the voltage application unit 20 is made to apply a voltage between the cathode electrode 11 and the anode electrode 15 so that a current flows from the cathode electrode 11 to the anode electrode 15. While applying the voltage, the current measurement unit 30 is made to measure the current.

[0068] In this embodiment, the voltage application step S12 is performed under the conditions of an applied voltage of 150 mV and an application time of 60 seconds, and the current is measured, but the disclosure is not limited to these conditions.

[0069] In this embodiment, the current being measured is generated by ion conduction, not by a redox reaction. Therefore, it is possible to determine the applied voltage without considering the voltage required to trigger a redox reaction (i.e., the redox potential of the substances in the system). The voltage application time should be set considering the applied voltage, allowing sufficient time for the conduction of the target ions contained in the sample S to be completed.

[0070] (calculation process) The calculation step S13 is a step in which the current value measured in the voltage application step S12 is integrated along the voltage application time to calculate the amount of electricity.

[0071] In this embodiment, the current measuring unit 30 is made to calculate the amount of electricity. Since the amount of electricity corresponds to the area under the curve (AUC) in a graph with the current value on the vertical axis and the voltage application time on the horizontal axis, as an example, the amount of electricity may be calculated by having the current measuring unit 30 calculate the area under the curve.

[0072] In this embodiment, the amount of the target ion in the sample S is determined in the subsequent correction step S14, but the disclosure is not limited to this configuration. In one embodiment in which the correction step S14 is not performed, the amount of the target ion may be determined in the calculation step S13. The amount of the target ion can be determined by using a calculation method known in coulometric titration based on the calculated amount of electricity. For example, the amount of the target ion may be determined by dividing the amount of electricity by the valence of the target ion.

[0073] (correction process) The correction step S14 is a step in which the amount of electricity calculated in the calculation step S13 is divided by the valence of the target ion, and the resulting value is multiplied by a predetermined constant to determine the amount of the target ion.

[0074] The ion sensor 10 according to this embodiment has excellent physical stability and is less prone to a decrease in electrolysis efficiency. In other words, the ion sensor 10 tends to maintain a constant electrolysis efficiency. Therefore, even after the ion sensor 10 has been energized once, or after the ion sensor 10 has been subjected to external force during the flow process, it is possible to quantify the target ions in the sample S with higher accuracy by performing a correction by multiplying by a predetermined constant according to the electrolysis efficiency. The electrolysis efficiency should be evaluated during the design or manufacturing of the ion sensor 10.

[0075] In the correction step S14, first, the amount of electricity calculated in the calculation step S13 is divided by the valence of the target ion. The obtained value corresponds to the amount of target ions assuming that the electrolysis efficiency is 100% (i.e., that the entire amount of current is generated by ion conduction). Next, in this embodiment, the amount of target ions is determined by multiplying the obtained value by the electrolysis efficiency, which is a predetermined constant. For example, if the electrolysis efficiency of the ion sensor 10 is evaluated to be 96%, then the obtained value should be multiplied by 0.96 as a constant.

[0076] In this disclosure, the predetermined constant used in the multiplication is not limited to the electrolysis efficiency, but may be determined in accordance with, for example, corrections that take into account the degradation of the ion sensor 10 over time and the type of target ion, in addition to the electrolysis efficiency.

[0077] [Modified example of Embodiment 1] An ion quantification device 100A according to a modified example of Embodiment 1 will be described with reference to Figure 8. Figure 8 is a schematic diagram showing the configuration of an ion quantification device 100A according to a modified example of Embodiment 1 of this disclosure. For the sake of explanation, components having the same function as those described in the above embodiments will be denoted by the same reference numerals, and their descriptions will not be repeated.

[0078] As shown in Figure 8, the ion quantification device 100A comprises an ion sensor 10A, a voltage application unit 20 and a current measurement unit 30 connected to the cathode electrode 11A and anode electrode 15A of the ion sensor 10A, and a sample container 12A.

[0079] The ion sensor 10A comprises a cathode electrode 11A and a laminate 101A. The laminate 101A includes a cation receiving layer 13A, a chloride ion conducting layer 14A, and an anode electrode 15A in that order.

[0080] The cathode electrode 11A, cation receiving layer 13A, chloride ion conducting layer 14A, and anode electrode 15A each have the same configuration as the cathode electrode 11, cation receiving layer 13, chloride ion conducting layer 14, and anode electrode 15 of Embodiment 1, except for their shape. In this modified example, the cathode electrode 11A and anode electrode 15A are rod-shaped. The cation receiving layer 13A and chloride ion conducting layer 14A are formed on the surface of the rod-shaped anode electrode 15A and are cylindrical with an open top and a closed bottom.

[0081] The sample container 12A is a component for providing a sample chamber SRA between the cathode electrode 11A and the cation receiving layer 13A. The sample chamber SRA is a space for storing the sample S and is in contact with the cathode electrode 11A and the cation receiving layer 13A. In this modified example, a glass beaker is used as the sample container 12A.

[0082] In this modified example, the liquid sample S is poured into the sample container 12A, and the cathode electrode 11A and the laminate 101A are inserted into the sample S to perform the introduction step S11 of the ion quantification method M100. In this modified example, the voltage application step S12, the calculation step S13, and the correction step S14 can be performed in the same manner as in Embodiment 1.

[0083] [Embodiment 2] Embodiment 2 of this disclosure will be described with reference to the drawings. For the sake of convenience, components having the same function as those described in the above embodiment will be denoted by the same reference numerals, and their descriptions will not be repeated.

[0084] The ion quantification apparatus 200 according to this embodiment will be described with reference to Figure 9. Figure 9 is a schematic diagram showing the configuration of the ion quantification apparatus 200 according to Embodiment 2 of this disclosure. The ion quantification apparatus 200 is an item for coulometric titration to quantify the target ions contained in a sample S. The sample S and target ions according to this embodiment are the same as those described in the above embodiment, so their description will not be repeated.

[0085] As shown in Figure 2, the ion quantification device 200 includes an ion sensor 40 and a voltage application unit 20 and a current measurement unit 30 connected to the cathode electrode 11 and anode electrode 15 of the ion sensor 40. The configuration of the voltage application unit 20 and the current measurement unit 30 according to this embodiment is the same as that described in the above embodiment, so that description will not be repeated.

[0086] The ion sensor 40 according to this embodiment is an article for coulometric titration to quantify target ions contained in a sample S. As shown in Figure 9, the ion sensor 10 comprises a cathode electrode 11, a spacer 12, and a laminate 201 in that order. The laminate 201 includes a cation receiving layer 13, a chloride ion conducting layer 14, and an anode electrode 15 in that order, and further includes a crosslinked polymer layer 16 between the cation receiving layer 13 and the chloride ion conducting layer 14. The configurations of the cathode electrode 11, spacer 12, cation receiving layer 13, and anode electrode 15 are the same as those described in the above embodiment, so their description will not be repeated.

[0087] (Cross-linked polymer layer) The crosslinked polymer layer 16 is provided between the cation receiving layer 13 and the chloride ion conducting layer 14. The crosslinked polymer layer 16 is a layer comprising (I) a third organic phase capable of conducting chloride ions and a crosslinked polymer supporting the third organic phase, or (II) a crosslinked polymer capable of conducting chloride ions. In this embodiment, since the crosslinked polymer layer 16 supports the cation receiving layer 13 and the chloride ion conducting layer 14, the mechanical strength of the ion sensor 10 is improved and its physical stability is enhanced. Furthermore, although it is difficult to bring the crosslinked polymer layer 16 into close contact with the electrode, the chloride ion conducting layer 14 is located between the crosslinked polymer layer 16 and the anode electrode 15, so that the adhesion between these three layers remains high.

[0088] In (I), the third organic phase may contain a first component, which is a non-volatile organic compound with a high dielectric constant. When the third organic phase contains the first component, its function of conducting chloride ions is enhanced. An example of the first component of the third organic phase is the same as an example of the first component of the first organic phase, and its explanation will not be repeated.

[0089] In (I), when the third organic phase is used as a liquid, the third organic phase may further contain an organic solvent that dissolves other components as a second component. An example of the second component of the third organic phase is the same as the example of the fifth component of the first organic phase, and its explanation will not be repeated.

[0090] In (I), the crosslinked polymer supporting the third organic phase is not particularly limited as long as it supports the third organic phase and is not dispersed in the first and second organic phases. Examples of polymers supporting the third organic phase include polystyrene / divinylbenzene copolymers and polystyrene / polymethyl methacrylate / divinylbenzene copolymers.

[0091] In (II), known anion exchange resins can be used as crosslinked polymers capable of conducting chloride ions. Examples of anion exchange resins include resins in which anion exchange groups such as ammonium cations or imidazolium cations are bonded to a hydrocarbon main chain skeleton composed of polystyrene, polyethersulfone, polyphenylene, or other copolymers.

[0092] The anion exchange resin may be either a strongly basic anion exchange resin or a weakly basic anion exchange resin, but a strongly basic anion exchange resin is preferred from the viewpoint of maintaining high ionic conductivity over a wide temperature range. An example of a strongly basic anion exchange resin is a copolymer of a polymerizable monomer having a hydrocarbon group to which a quaternary cation is bonded and a crosslinkable monomer.

[0093] Examples of quaternary bases in polymerizable monomers include tetraalkylammonium cations and phosphonium cations. The counterion of a quaternary cation is not limited to a chloride ion, but may be any anion. Examples of counterions of quaternary cations include: halide ions such as chloride ions and bromide ions; inorganic anions such as sulfate ions, nitrate ions, and nitrite ions; and carboxylate ions such as acetate ions, lactate ions, and citrate ions.

[0094] Examples of hydrocarbon groups in polymerizable monomers include styrene derivatives and methacrylic acid derivatives. Examples of styrene derivatives include 4-methylstyrene, 4-ethylstyrene, 4-propylstyrene, 4-butylstyrene, 4-pentylstyrene, and 4-hexylstyrene, 4-chloromethylstyrene, and 4-(trimethylammoniummethyl)styrene.

[0095] Examples of crosslinkable monomers include divinyl compounds such as divinylbenzenes, divinyl sulfones, divinylbiphenyls, trivinylbenzenes, divinylnaphthalenes, and divinylpyridines.

[0096] The crosslinked polymer supporting the third organic phase and the crosslinked polymer capable of conducting chloride ions are preferably selected from the group consisting of styrene-divinylbenzene copolymers and polymethacrylic acid derivative-crosslinkable monomers. These crosslinked polymers are preferred from the viewpoint that they can be polymerized under relatively mild reaction conditions and have sufficient mechanical strength.

[0097] In this embodiment, the crosslinked polymer layer 16 is a thin film of (4-butylstyrene)-trimethylammonium chloride-divinylbenzene copolymer, which is a crosslinked polymer capable of conducting chloride ions.

[0098] (Chloride ion conductive layer in Embodiment 2) The chloride ion conductive layer 14 is provided between the chloride ion conductive layer 14 and the anode electrode 15. In this embodiment, the chloride ion conductive layer 14 includes a second organic phase as a phase capable of conducting chloride ions.

[0099] In this embodiment, the cation-receiving layer 13 contains a first organic phase, and the chloride ion-conducting layer 14 contains a second organic phase. In other words, both the cation-receiving layer 13 and the chloride ion-conducting layer 14 contain organic phases. This is advantageous from the viewpoint of simplifying the layer structure of the ion sensor 10 and improving the mass productivity of the ion sensor 10. On the other hand, since the cation-receiving layer 13 and the chloride ion-conducting layer 14, both of which contain organic phases, are separated by the cross-linked polymer layer 16, migration of components other than ion conduction is prevented between the first organic phase of the cation-receiving layer 13 and the second organic phase of the chloride ion-conducting layer 14. The ion sensor 10 according to this embodiment has excellent long-term storage properties because interlayer component migration is prevented.

[0100] Other components of the chloride ion conductive layer 14 are the same as those described in the above embodiment, and therefore will not be repeated.

[0101] [Additional Notes] The present invention is not limited to the embodiments described above, and various modifications are possible within the scope of the claims. Embodiments obtained by appropriately combining the technical means disclosed in different embodiments are also included in the technical scope of the present invention.

[0102] 〔summary〕 As can be understood from the above description, this disclosure encompasses the following aspects:

[0103] Embodiment 1: An ion sensor for coulometric titration to quantify a target ion contained in a sample (S), comprising a cathode electrode (11, 11A) and a laminate (101, 101A, 201), wherein the laminate includes, in this order, a cation-receiving layer (13, 13A) containing a first organic phase that accepts cations contained in the sample, a chloride ion conducting layer (14, 14A) containing chloride ions and cations and capable of conducting chloride ions, and an anode electrode (15, 15A) that emits anions when it accepts electrons, an ion sensor (10, 10A, 40). According to this embodiment, in coulometric titration, an electric current is generated in the ion sensor due to the conduction of cations contained in the sample and chloride ions contained in the chloride ion conducting layer. Therefore, compared to conventional technology that utilizes oxidation-reduction reactions instead of ion conduction for current generation, the cation-receiving layer and the chloride ion conducting layer tend to exhibit high shape stability and maintain interlayer adhesion even when current is applied to the ion sensor. Therefore, the ion sensor according to this embodiment has excellent physical stability.

[0104] Embodiment 2: An ion sensor (40) according to Embodiment 1, wherein the laminate (201) further includes a crosslinked polymer layer (16) between the cation-receiving layer and the chloride ion-conducting layer, the crosslinked polymer layer (16) comprising (I) a third organic phase capable of conducting chloride ions and a crosslinked polymer supporting the third organic phase, or (II) a crosslinked polymer capable of conducting chloride ions. According to this embodiment, since the crosslinked polymer layer supports the cation-receiving layer and the chloride ion-conducting layer, the mechanical strength of the ion sensor is improved and its physical stability is further enhanced. In addition, since the chloride ion-conducting layer is located between the crosslinked polymer layer and the anode electrode, the adhesion between these three layers is maintained at a high level.

[0105] Embodiment 3: An ion sensor according to Embodiment 2, wherein the chloride ion conducting layer includes a second organic phase. According to this embodiment, the cation receiving layer and the chloride ion conducting layer, both containing organic phases, are separated by a crosslinked polymer layer, and the migration of components other than ion conduction between the cation receiving layer and the chloride ion conducting layer is prevented, so the ion sensor has excellent long-term storage properties.

[0106] Embodiment 4: An ion sensor according to Embodiment 2 or 3, wherein the crosslinked polymer supporting the third organic phase and the crosslinked polymer capable of conducting chloride ions are selected from the group consisting of styrene-divinylbenzene copolymer and polymethacrylic acid derivative-crosslinkable monomer. According to this embodiment, a crosslinked polymer layer is provided that employs a polymer that can be polymerized under relatively mild reaction conditions and has superior mechanical strength.

[0107] Embodiment 5: An ion sensor according to any one embodiment of Embodiments 1 to 4, wherein the chloride ion conducting layer includes a second organic phase, and the cation contained in the chloride ion conducting layer is selected from the group consisting of tetraalkylammonium cation, trialkylammonium cation, and tetraalkylphosphonium cation. According to this embodiment, the tendency of the cation contained in the chloride ion conducting layer to undergo oxidation-reduction reactions is reduced, thereby improving the chemical stability of the ion sensor and slowing down the decrease in the electrolytic efficiency of the ion sensor due to deterioration over time such as air oxidation.

[0108] Embodiment 6: An ion sensor according to any one of Embodiments 1 to 5, wherein the target ion is a cation, and the first organic phase includes an ionophore that specifically accepts the target ion. According to this embodiment, an ion sensor is provided that can selectively quantify the target ion because the cation-accepting layer specifically accepts the target ion.

[0109] Embodiment 7: An ion sensor according to any one of Embodiments 1 to 6, wherein the sample is a biological sample. The ion sensor according to this embodiment has excellent physical stability and is less likely to experience a decrease in electrolysis efficiency even when subjected to external forces, making it suitable as an ion sensor for biological samples that are used as disposable items and are often subjected to external forces such as vibration during distribution.

[0110] Embodiment 8: A method for quantifying a target ion using an ion sensor according to any one embodiment of Embodiments 1 to 7, comprising: an introduction step (S11) of introducing the sample between the cathode electrode and the cation receiving layer; a voltage application step (S12) of measuring the current flowing between the cathode electrode and the anode electrode while applying a voltage between them; and a calculation step (S13) of calculating an electric quantity by integrating the current value measured in the voltage application step along the voltage application time. This embodiment provides a method for quantifying a target ion using an ion sensor with excellent physical stability.

[0111] Embodiment 9: An ion quantification method according to Embodiment 8, further comprising a correction step (S14) in which the amount of electricity calculated in the calculation step is divided by the valence of the target ion, and the amount of the target ion is determined by multiplying the obtained value by a predetermined constant. According to this embodiment, it is possible to quantify the target ion in a sample with higher accuracy. The ion sensor according to this embodiment has excellent physical stability and is less prone to a decrease in electrolysis efficiency. Therefore, even after the ion sensor has been energized once, or after the ion sensor has been subjected to external force during the flow process, correction using a predetermined constant according to the electrolysis efficiency is effective.

[0112] Embodiment 10: An ion quantification device comprising an ion sensor according to any one embodiment of Embodiments 1 to 7, and a voltage application unit (20) and a current measurement unit (30) connected to the cathode electrode and the anode electrode. According to this embodiment, a device for quantifying target ions is provided, which is equipped with an ion sensor that has excellent physical stability. [Examples]

[0113] An embodiment of this disclosure is described below. In this disclosure, ion sensors of the examples and comparative examples were fabricated, and their physical stability against shaking and chemical stability against degradation over time were evaluated.

[0114] [Example 1] Thin silver electrodes, thin silver / silver chloride electrodes (dimensions 1cm × 1cm × 0.5mm), and thin resin plates with through holes (diameter 3mm) (dimensions 1cm × 1cm × 0.5mm) were prepared as spacers. The silver / silver chloride electrodes were prepared by immersing a silver plate in an aqueous NaCl solution and performing electrolysis at 1.5V. Valinomycin at a final concentration of 20mM was dissolved in o-nitrophenyl octyl ether (NPOE), and the solution was impregnated into a fluororesin membrane filter (dimensions 1cm × 1cm, manufactured by Toyo Roshi Co., Ltd., product name J100A-25A) to prepare a cation receiving layer. In addition, trioctylmethylammonium chloride at a final concentration of 20mM was dissolved in another NPOE, and the solution was impregnated into another membrane filter of the same type to prepare a chloride ion conducting layer. A thin film of strongly basic anion exchange resin (dimensions 1 cm × 1 cm × 0.03 mm, manufactured by Tokuyama Corporation, product name A201) was prepared as the crosslinked polymer layer.

[0115] A silver electrode was laminated on one side of the spacer and fixed at one edge. The cation-receiving layer, cross-linked polymer layer, chloride ion-conducting layer, and silver / silver chloride electrode were laminated in this order and the whole assembly was fixed to prepare the laminate. The side of the spacer facing away from the silver electrode and the side of the laminate facing the cation-receiving layer were laminated and fixed at one edge to fabricate the ion sensor of Example 1.

[0116] In the measurement example, as shown in Figures 3-6, each layer was rotated, 3.5 μL of the sample was dropped into the through-hole of the spacer, the silver electrode was closed, and each layer was compressed and fixed, using the ion sensor of Example 1.

[0117] [Comparative Example 1] An ion sensor of Comparative Example 1 was fabricated according to Example 5 described in Patent Document 1. Specifically, a metal oxide (Na) was used. 0.33 A paste containing MnO2, a solid electrolyte (β-alumina), a conductive material (acetylene black), and a binder (polyvinylidene fluoride) was applied to carbon paper using a squeegee to prepare an insertion coating film. An organic phase holding layer was prepared by impregnating a Teflon porous membrane with NPOE to which 0.01 M BTPPATFPB was added as a supporting electrolyte.

[0118] An organic phase-retaining layer was laminated onto an insertion coating film, and a sheet with through-holes for holding the sample was laminated on top of that. Then, a silver / silver chloride electrode was placed on top of the sheet. In addition, another silver / silver chloride electrode, organic phase-retaining layer, sheet, and silver / silver chloride electrode were laminated to fabricate the ion sensor of Comparative Example 1.

[0119] In the measurement example, the silver / silver chloride electrode on the sheet was opened, 1 μL of the sample was dropped into the through-hole of the sheet, then the silver / silver chloride electrode was closed, and each layer was compressed and fixed, and the ion sensor of Comparative Example 1 was used.

[0120] [Measurement Example 1: Evaluation of physical stability against shaking] The ion sensors of the examples and comparative examples were subjected to vibration using a shaking device (Miyamoto Riken Kogyo Co., Ltd., product name: Powerful Shaker) under the conditions of a shaking amplitude of 80 mm, a rotation speed of 60 rpm, and a shaking time of 1 hour. After shaking, coulometric titration was performed using a 0.1 mM KCl aqueous solution as a sample with the ion sensors of the examples and comparative examples, both before and after shaking. The coulometric titration conditions were an applied voltage of 150 mV and an application time of 60 seconds. The amount of electricity was calculated from the integral value of the measured current value.

[0121] The electrolysis efficiency (%) was calculated using the following formula. The theoretical electric charge (μC) is calculated based on the KCl concentration of the sample. + This is the amount of electricity required for all of the cations to move to the cation receiving layer, which was 33.8 μC in this measurement example. The measurement results for the electrolysis efficiency are shown in Table 1. Electrolysis efficiency (%) = Electrolysis amount (μC) / Theoretical electrolysis amount (μC)

[0122] Table 1 shows the measurement results of the electrolysis efficiency. The smaller the change in electrolysis efficiency before and after shaking, the more resistant the ion sensor is to external forces such as shaking, and the better its physical stability.

[0123] [Table 1]

[0124] As shown in Table 1, the ion sensor of Example 1 shows less change in electrolysis efficiency before and after shaking compared to the ion sensor of Comparative Example 1. From this result, it can be seen that the ion sensor for coulometric titration to quantify target ions contained in a sample according to the present disclosure, comprising a cathode electrode and a laminate, wherein the laminate comprises, in this order, a cation-receiving layer containing a first organic phase that accepts cations contained in the sample, a chloride ion-conducting layer containing chloride ions and cations and a second organic phase or aqueous phase capable of conducting chloride ions, and an anode electrode that emits anions when it accepts electrons, exhibits excellent physical stability.

[0125] [Measurement Example 2: Evaluation of Chemical Stability Against Degradation Over Time] The ion sensors of the prepared examples and comparative examples were stored in air at a temperature of 25°C. One day, seven days, fourteen days, and twenty-eight days after ion sensor preparation, coulometric titration was performed using a 0.1 mM KCl aqueous solution as a sample with each of the stored ion sensors of the examples and comparative examples, and the electrolytic efficiency was calculated. The coulometric titration conditions and the method for calculating the electrolytic efficiency were the same as those in Measurement Example 2.

[0126] Table 2 shows the measurement results of the electrolysis efficiency. The smaller the change in electrolysis efficiency over time, the more resistant the ion sensor is to air oxidation in the atmosphere and the better its chemical stability.

[0127] [Table 2]

[0128] In the ion sensor of Comparative Example 1, the oxidation-reduction reaction of the metal oxide mediates the electric current. As shown in Table 2, the electrolytic efficiency of the ion sensor of Comparative Example 1 changed significantly and irregularly over time. This is presumed to be due to the fact that air oxidation of the metal oxide and its reverse reaction proceed easily in the atmosphere, and the oxidation state of the metal oxide is unstable. In contrast, the electrolytic efficiency of the ion sensor of Example 1 did not change over time, or decreased very slowly. This is thought to be because the ion sensor of Example 1 utilizes stable chloride ions and ion transfer of cations in the sample to generate electric current, and is therefore substantially unaffected by air oxidation. From these results, it can be said that the ion sensor according to this disclosure has excellent chemical stability. [Explanation of Symbols]

[0129] 10,10A,40 Ion Sensor 11,11A Cathode electrode 12 Spacers 12A Sample container 13,13A Cation-receiving layer 14,14A Chloride ion conductive layer 15,15A Anode electrode 16 Cross-linked polymer layer 20 Voltage application section 30 Current measurement section 100, 100A, 200 Ion Determination Apparatus 101, 101A, 201 laminate 111,151 Connection part 121 Through hole SR, SRA Sample Room

Claims

1. An ion sensor for coulometric titration to quantify target ions contained in a sample, The structure comprises a cathode electrode and a laminate, The laminated body is A cation-receiving layer comprising a first organic phase that accepts cations contained in the sample, A chloride ion conductive layer containing chloride ions and cations, capable of conducting chloride ions, An anode electrode that emits an anion when it accepts an electron, An ion sensor containing these elements in this order.

2. The laminate is provided with the cation receiving layer and the chloride ion conducting layer, (I) A third organic phase capable of conducting chloride ions, and a crosslinked polymer supporting the third organic phase, (II) Crosslinked polymers capable of conducting chloride ions, Further comprising a crosslinked polymer layer containing, The ion sensor according to claim 1.

3. The chloride ion conductive layer includes a second organic phase. The ion sensor according to claim 2.

4. The crosslinked polymer supporting the third organic phase and the crosslinked polymer capable of conducting chloride ions are selected from the group consisting of styrene-divinylbenzene copolymer and polymethacrylic acid derivative-crosslinkable monomer. The ion sensor according to claim 2 or 3.

5. The chloride ion conductive layer includes a second organic phase. The cation contained in the chloride ion conductive layer is selected from the group consisting of tetraalkylammonium cation, trialkylammonium cation, and tetraalkylphosphonium cation. The ion sensor according to any one of claims 1 to 4.

6. The aforementioned target ion is a cation. The first organic phase includes an ionophore that specifically accepts the target ion. The ion sensor according to any one of claims 1 to 5.

7. The aforementioned sample is a biological sample. The ion sensor according to any one of claims 1 to 6.

8. A method for quantifying a target ion using an ion sensor according to any one of claims 1 to 7, An introduction step of introducing the sample between the cathode electrode and the cation receiving layer, A voltage application step in which a voltage is applied between the cathode electrode and the anode electrode, and the current flowing between the cathode electrode and the anode electrode is measured, A calculation step which involves integrating the current value measured in the voltage application step along the voltage application time to calculate the amount of electric charge, A method for determining ions, including the method described above.

9. The calculation further includes a correction step in which the amount of electricity calculated in the calculation step is divided by the valence of the target ion, and the resulting value is multiplied by a predetermined constant to determine the amount of the target ion. The method for determining ions according to claim 8.

10. An ion sensor according to any one of claims 1 to 7, A voltage application unit and a current measurement unit connected to the cathode electrode and the anode electrode, An ion quantification device equipped with the following features.

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