Ion-selective electrode, and electrolyte concentration measuring device

Abstract

The present disclosure relates to an ion-selective electrode based on an ion exchange membrane having a high-density of fixed charges, and in order to improve ion selectivity and stability over time using a simpler method, proposes an ion-selective electrode (see Fig. 2) for measuring a target ion contained in a sample solution, the ion-selective electrode comprising an electrode enclosure accommodating an internal solution, an internal electrode partially in contact with the internal solution, and an ion sensitive film separating the sample solution and the internal solution, wherein: the ion sensitive film is in contact with the sample solution on at least a portion of a first surface and is in contact with the internal solution on at least a portion of a second surface different from the first surface; and the first surface of the ion sensitive film is covered by an inert layer that suppresses an ion exchange reaction between the ion sensitive film and the sample solution.

Description

Ion-selective electrode and electrolyte concentration measuring device

[0001] The present disclosure relates to an ion-selective electrode and an electrolyte concentration measuring device including the same.

[0002] Potentiometric measurements using ion-selective electrodes (ISEs) can quickly and easily quantify the concentration of specific ions in a liquid, and are therefore used in a wide range of fields, including water quality analysis and medicine. In particular, in the medical field, where metabolic reactions in living organisms are closely related to ion concentrations, quantifying specific ions contained in biological samples such as serum and urine is used to diagnose conditions such as hypertension, kidney disease, and neurological disorders. Because clinical testing requires the continuous analysis of a large number of samples, high-throughput automated analyzers and electrolyte concentration measuring devices equipped with ion-selective electrodes are routinely used.

[0003] The measurement items of electrolyte concentration measuring devices are mainly cations such as sodium ions and potassium ions, and anions such as chloride ions. Regarding cations, compounds (ionophores) that selectively capture specific cations, such as crown ethers and valinomycin, have been discovered. Ion-sensitive membranes of cation-selective electrodes for sodium, potassium, etc. generally contain these ionophores, and have high ion selectivity.

[0004] On the other hand, for anions, there are no ionophores suitable for ion-selective electrodes in automated analyzers, which require high-throughput, fast response, and long-term stability, and various types of sensitive membranes have been used. One such example is a Cl ion-sensitive membrane based on an ion-exchange membrane with a high charge density. For example, Patent Document 1 discloses a chloride ion-sensitive membrane based on an anion-exchange membrane, the surface of which is coated with a condensate of metaphenylenediamine and formaldehyde. Patent Document 2 also discloses an anion-selective electrode in which the surface of the anion-exchange membrane that comes into contact with the sample solution is coated with an epoxyamine resin that is anion-responsive.

[0005] Patent No. 3812049 Patent No. 6783704

[0006] In some cases, a sample contains many types of ions other than the target ions, and these types of ions interfere with measuring the concentration of the target ions. For example, blood serum (a sample), which is one of the analytical targets in clinical testing, contains chloride ions (Cl) as anions. － ) as well as bicarbonate ions (HCO ３ － ), which interferes with the measurement of chloride ion concentration. Therefore, it is important for a chloride ion-selective electrode to have low selectivity for bicarbonate ions.

[0007] On the other hand, as mentioned above, it is technically more difficult to improve the selectivity of an anion-selective electrode than that of a cation-selective electrode because, unlike cations, no ionophores suitable for anion-selective electrodes have been discovered.

[0008] Furthermore, when cations are to be measured, an ion-sensitive membrane containing the above-mentioned ionophore is usually used, but an ion-sensitive membrane not containing an ionophore can also be used for the ion-selective electrode.

[0009] In view of the above circumstances, the present disclosure provides a technology for improving the ion selectivity and stability over time in a simpler manner for an ion-selective electrode based on an ion exchange membrane having a high density of fixed charges.

[0010] In order to solve the above problems, the present disclosure proposes an ion-selective electrode for measuring target ions contained in a sample liquid, comprising an electrode housing that contains an internal liquid, an internal electrode that is partially in contact with the internal liquid, and an ion-sensitive membrane that separates the sample liquid from the internal liquid, wherein at least a portion of a first surface of the ion-sensitive membrane is in contact with the sample liquid and at least a portion of a second surface that is different from the first surface is in contact with the internal liquid, and the first surface of the ion-sensitive membrane is coated with an inert layer that suppresses ion exchange reactions between the ion-sensitive membrane and the sample liquid.

[0011] Further features related to the present disclosure will become apparent from the description of this specification and the accompanying drawings. Also, aspects of the present disclosure are achieved and realized by the elements and combinations of various elements and the aspects of the following detailed description and the appended claims. The description of this specification is merely exemplary and does not limit the scope or application of the claims of the present disclosure in any way.

[0012] According to the technology of the present disclosure, it is possible to improve the ion selectivity and stability over time of an ion-selective electrode based on an ion exchange membrane having a high density of fixed charges in a simpler manner.

[0013] 1A is a front view of a flow-type ion-selective electrode 10. FIG. 1B is a diagram showing an example of the configuration of the flow-type ion-selective electrode 10 in the AA' cross section of FIG. 1A. FIG. 1C is a diagram showing an example of the configuration of the flow-type ion-selective electrode 10 in the BB' cross section perpendicular to the AA' cross section. FIG. 1C is a schematic enlarged view of the dotted rectangle 17-1 portion of FIG. 1C, showing a characteristic layer structure of the ion-sensitive membrane 17 according to the present embodiment. FIG. 1C is a diagram showing an example of the configuration of an electrolyte concentration measuring device (flow type) 100 including an ion-selective electrode according to the present disclosure. FIG. 1C is a flowchart for explaining the operation at the start-up of the electrolyte concentration measuring device 100. FIG. 1C is a flowchart for explaining the operation at the time of continuous analysis in the electrolyte concentration measuring device 100. FIG. 1C is a schematic enlarged view of the dotted rectangle 17-1 portion of FIG. 1C, showing a characteristic layer structure of the ion-sensitive membrane 17 according to the present embodiment. FIG. 1C is an enlarged view of the dotted rectangle 17-1 portion of FIG. 1C, showing a layer structure of the ion-sensitive membrane of Comparative Example 1. FIG. 1C is an enlarged view of the dotted rectangle 17-1 portion of FIG. 1C, showing a layer structure of the ion-sensitive membrane of Comparative Example 2. 10 is a diagram showing an example of a cross-sectional configuration of a stick-type ion-selective electrode 20 according to a third embodiment; FIG. 11 is a diagram showing a comparison result of response behaviors to aqueous solutions containing various concentrations and types of ions for an ion-selective electrode 10 having the structure shown in the first embodiment, in which PVC is used as the material for the inactive layer 5, and an electrode of Comparative Example 1; FIG. 12 is a diagram showing a schematic diagram of the ion-sensitive membrane of Comparative Example 1 and the ion composition inside the sample solution; FIG. 13 is a diagram showing a schematic diagram of the ion-sensitive membrane 17 of the ion-selective electrode 10 having the inactive layer 5 and the ion composition inside the sample solution; and FIG. 14 is a diagram showing a comparison result of response behaviors to aqueous solutions containing various concentrations and types of ions for an ion-selective electrode 10 having the structure shown in the first embodiment, in which PVC is used as the material for the inactive layer 5; and FIG. 15 is a diagram showing a schematic diagram of the ion-sensitive membrane 17 of Comparative Example 1 and the ion composition inside the sample solution; and FIG. 16 is a diagram showing a comparison result of response behaviors to aqueous solutions containing various concentrations and types of ions for an ion-selective electrode 10 having the inactive layer 5; and FIG. 17 is a diagram showing a comparison result of response behaviors to aqueous solutions containing various concentrations and types of ions. － 7 is a diagram showing the results of calculating the selectivity coefficients of each interfering ion for chloride ions (Cl ). － ) to bicarbonate ion (HCO ３ － 8 is a graph showing the measurement results of the selectivity coefficient of chloride ions (Cl ) for the ion selective electrode having the structure according to Comparative Example 2 (see FIG. 8 ) and the ion selective electrode having the structure according to the second embodiment (see FIG. 6 ). －) to bicarbonate ion (HCO ３ － ) A graph showing the measurement results of the selectivity coefficient.

[0014] This embodiment relates to an ion-selective electrode for measuring the ion concentration in a liquid and an electrolyte concentration measuring device including the electrode. The ion-sensitive membrane constituting the ion-selective electrode according to each embodiment includes a high-charge-density ion-exchange membrane and an inactive layer (a layer made of a material that does not respond to ions) formed on the surface of the ion-exchange membrane that contacts the sample containing the ions to be measured. By adopting this structure, it is possible to suppress the ion exchange phenomenon and achieve ion selectivity characteristics closer to those of the ion-sensitive membrane itself.

[0015] Hereinafter, embodiments of the present disclosure will be described with reference to the accompanying drawings. In the accompanying drawings, functionally identical elements may be designated by the same numerals. Note that the accompanying drawings illustrate specific embodiments and implementation examples according to the principles of the present disclosure, but these are for understanding the present disclosure and are not to be used to interpret the present disclosure in any way as being limiting.

[0016] Although the present embodiment has been described in sufficient detail to enable those skilled in the art to practice the present disclosure, it should be understood that other implementations and forms are possible, and that changes in configuration and structure and substitutions of various elements are possible without departing from the scope and spirit of the technical ideas of the present disclosure. Therefore, the following description should not be interpreted as being limited thereto.

[0017] (1) First Embodiment The first embodiment discloses a flow-type ion-selective electrode 10. Here, the embodiment will be described using a chloride ion-selective electrode as an example, but the technology of the present disclosure can also be used to select other types of ions (e.g., Br － , I － , C.N. － , Cd ２＋ , Cu ２＋ , Ag ＋ , S ２－ , F － , K. ＋ , Ca ２＋ , NO ３ － , N.H. ４ ＋ , Na＋ The present invention is also applicable to ion-selective electrodes for measuring the concentration of various organic compounds, such as ammonium hydroxide, ammonium nitrate ... and ammonium nitrate.

[0018] 1A to 1C are diagrams showing an example of the overall configuration of a flow-type ion-selective electrode 10 according to a first embodiment. Fig. 1A is a front view of the flow-type ion-selective electrode 10. Fig. 1B is a diagram showing an example of the configuration of the flow-type ion-selective electrode 10 in the A-A' cross section of Fig. 1A. Fig. 1C is a diagram showing an example of the configuration of the flow-type ion-selective electrode 10 in the B-B' cross section perpendicular to the A-A' cross section.

[0019] The flow-type ion-selective electrode 10 has an electrode housing 11, an internal electrode 13, a flow path 12 that penetrates the electrode housing 11, a gasket 15, an internal gel storage section that stores an internal gel 16, an ion-sensitive membrane 17, and a lid 18.

[0020] A sample solution to be measured passes through the flow path 12. The ion-sensitive membrane 17 is disposed so as to be in contact with the sample solution. The internal gel (or internal solution) 16 contains an electrolyte and is contained within the electrode housing 11 so as to fill the internal gel container. The internal electrode 13 is disposed so as to be in contact with the internal gel 16. A lid 18 is attached to the opening of the electrode housing 11 to confine the internal gel 16 within the electrode housing. A gasket 15 is disposed near the entrance / exit of the flow path 12 of the electrode housing 11 so as to be connected to an electrolyte concentration measurement device (electrolyte concentration analysis device) described below or the flow path of another electrode. The ion-selective electrode 10 having the above configuration is mounted on an electrolyte concentration measurement device. During measurement, the internal electrode 13 is connected to wiring on the device side, allowing the potential generated in response to the concentration of the target ions contained in the sample solution to be measured and the concentration of the target ions to be measured to be analyzed.

[0021] <Configuration Example of Ion-Sensitive Film 17> FIG. 2 is an enlarged schematic diagram of the dotted rectangle 17-1 in FIG. 1C, showing the characteristic layer structure of the ion-sensitive film 17 according to this embodiment.

[0022] (Electrode Manufacturing Procedure) (i) First, the ion-sensitive membrane 17 is based on an anion exchange membrane 1 having a high density of immobilized cations (it is an anion exchange membrane for measuring anions, and becomes a cation exchange membrane for measuring cations). The anion exchange membrane 1 has chloride ions (Cl) as counter ions. － )

[0023] (ii) A solution of a polymer, which will be described later, dissolved in tetrahydrofuran (THF), a low-boiling-point solvent, is applied to the surface of the ion-sensitive membrane 17 that comes into contact with the sample solution. The THF is then evaporated to form a thin layer of polymer on the surface of the ion-sensitive membrane 17. This layer is called the inactive layer 5. The method for forming the inactive layer 5 described here is one example, and other methods may also be used.

[0024] (iii) Then, the anion exchange membrane 1 is adhered to the electrode housing 11 so as to close the opening provided in the electrode housing 11 .

[0025] (iv) Next, the internal gel 16 is filled into the internal gel storage portion of the electrode housing 11 .

[0026] (v) After filling the internal gel 16, the lid 18 is welded to the electrode housing 11, and the internal electrode 13 is fixed so as to contact the internal gel 16. In order to suppress evaporation of water from the internal gel 16, the surface of the ion-sensitive membrane 17 on the side opposite to the flow path 12 may be coated with a resin or the like.

[0027] (Example of the configuration of anion exchange membrane 1) The anion exchange membrane 1 constituting the ion-sensitive membrane 17 can be a highly cross-linked polystyrene-based membrane having quaternary ammonium ions as anion exchange groups, and reinforced with a woven fabric of PVC (polyvinyl chloride) yarn.

[0028] However, the present invention is not limited to this membrane, and the ion exchange group may be a primary to tertiary amino group, the base material may be a hydrocarbon resin such as polyolefin or a fluorine-based resin instead of a styrene-based resin, etc. Furthermore, the reinforcing material may be other materials such as other polymer fibers or glass fibers, and the membrane may not have a reinforcing material.

[0029] Furthermore, the counter ions contained in the anion exchange membrane 1 are preferably the same type of ions as the ions to be measured, but may be other anions. Furthermore, the effects of the technology disclosed herein can be achieved even if the material is not that used for general ion exchange membranes, as long as the membrane has a high density of fixed charges. Here, high density means a charge density of approximately 0.1 to 10 mmol / g.

[0030] Note that a different type of ion-sensitive membrane from the ion-sensitive membrane 17 of the present disclosure is a membrane called a liquid membrane type. This generally involves dissolving a lipophilic salt as a fixed charge in a membrane such as soft PVC, and incorporating an ionophore or the like to improve ion selectivity. Such liquid membrane type ion-sensitive membranes have a charge density of approximately 0.001 to 0.1 mmol / g.

[0031] (Configuration Example of Inactive Layer 5) The inactive layer 5 functions to suppress the ion exchange reaction between the ion exchange membrane 1 and the sample solution. The inactive layer 5 is characterized by a charge density of, for example, 0.0001 mmol / g or less and being non-ion-responsive (composed of a material that is non-ion-responsive). In other words, the material for the inactive layer 5 is preferably an insulating material such as a general polymer that is water-insoluble so as not to dissolve in the sample solution. Furthermore, to maintain adhesion to the ion exchange membrane, a material of the same type as the membrane's base material or support material or a material with a solubility parameter value similar to that of the membrane's base material or support material is desirable. Furthermore, when forming the inactive layer 5 using a method such as that of this embodiment (when forming the inactive layer 5 by applying a solution of a polymer dissolved in tetrahydrofuran (THF) as described above), a material that is easily soluble in a low-boiling point solvent is desirable.

[0032] Examples of materials that can be used for the inactive layer 5 include poly(vinyl chloride) (PVC), ethylene / vinyl acetate copolymer, poly(vinyl formal), and mixed materials of a polymer and the plasticizer dioctyl adipate (DOA), such as PVC+DOA, ethylene / vinyl acetate copolymer+DOA, poly(ethyl methacrylate)+DOA, and poly(vinyl acetate)+DOA. Specific electrode performance will be described later. While all of these materials exhibit the effects of the technology disclosed herein, the present invention is not limited to these polymer materials and plasticizers. Any inactive material that does not respond to ions and suppresses the ion exchange reaction between the ion exchange membrane 1 and the sample solution can be used.

[0033] As described above, the material of the inactive layer 5 can be a polymer containing carbon and hydrogen as elements. Furthermore, elements such as chlorine and oxygen can be included to improve adhesion to the ion exchange membrane 1. However, the material is not limited to this, and any material that satisfies the above conditions (having the ability to suppress ion exchange reactions; having a charge density of 0.0001 mmol / g or less; and not responding to ions) can be used. Furthermore, in addition to polymeric materials, low-molecular-weight materials, inorganic materials, etc. may also be used, and composite materials in which multiple materials are mixed may also be used. Furthermore, the inactive layer 5 may be composed of multiple layers.

[0034] As mentioned above, the inactive layer 5 is made of an insulating material, but it must be formed to be appropriately thin in order to create a state in which ion permeation is not completely insulated. Specifically, if ion exchange is completely blocked, there will be no ion response, so a layer thickness of 10 μm or less is required. On the other hand, to obtain the effect of suppressing the ion exchange reaction, a layer thickness of 0.10 μm or more is required.

[0035] The ion-selective electrode 10 according to the present embodiment has an inactive layer 5 on the surface of the ion-exchange membrane 1, thereby suppressing the ion exchange reaction between the ion-exchange membrane 1 and the sample solution, thereby enabling the electrode characteristics during practical use to approach the inherent ion selectivity of the ion-sensitive membrane 17. Furthermore, in the case of a structure in which the surface of the ion-exchange membrane 1 is coated with an epoxyamine resin as disclosed in Patent Document 2, the epoxyamine resin itself is ion-responsive, and the response characteristics of the epoxyamine resin itself are the electrode characteristics. If the response characteristics of the epoxyamine resin deteriorate over time, the electrode characteristics will also deteriorate. Therefore, to achieve an ion-selective electrode that is stable over time, the epoxyamine resin itself must also have stable response characteristics over time. On the other hand, in the structure according to the present embodiment, the inactive layer 5 does not inherently have ion response, and therefore its characteristics are less likely to deteriorate. Furthermore, the inactive layer 5 only needs to function to suppress the ion exchange reaction between the ion-exchange membrane 1 and the sample solution. Therefore, as long as the above-mentioned certain conditions (having the ability to suppress ion exchange reactions; having a charge density of 0.0001 mmol / g or less; and not responding to ions) are met, a wide range of materials can be selected for the inactive layer 5. Furthermore, it is also possible to select a material that makes it difficult for components contained in the measurement sample to adhere to the membrane surface.

[0036] Although the present embodiment has been described with reference to a chloride ion-selective electrode, the present technology can also be applied to other anion-selective electrodes and cation-selective electrodes. Naturally, it is necessary to use an ion-exchange membrane 1 that is appropriate for the ions to be measured. For example, a cation-selective electrode requires the use of an ion-exchange membrane that has a fixed charge opposite to that of an anion-selective electrode (e.g., sulfonic acid or carboxylic acid group; ions in the ion-exchange membrane are fixed with negative ions, and positive ions (e.g., the ions to be measured) serve as counter ions).

[0037] <Configuration Example of Electrolyte Concentration Measuring Device> Figure 3 is a diagram showing a configuration example of an electrolyte concentration measuring device (flow type) 100 equipped with an ion-selective electrode according to the present disclosure. The electrolyte concentration measuring device 100 is a device that analyzes the concentrations of three types of ions, for example, Na, K, and Cl ions. The electrolyte concentration measuring device 100 includes a measuring unit 170, a potential measuring unit 171, a concentration calculating unit 172, an output unit 174, a device control unit 175, and an input unit 176.

[0038] The measurement unit 170 includes three ion-selective electrodes: a chloride (Cl) ion electrode 101, a potassium (K) ion electrode 102, and a sodium (Na) ion electrode 103; and a reference electrode 104. The dilution tank 110 of the measurement unit 170 is a cup for temporarily storing a diluted sample obtained by mixing a sample dispensed from a sample nozzle (not shown) with a diluent dispensed from a diluent supply nozzle 108, or an internal standard dispensed from an internal standard supply nozzle 109. The sipper nozzle 107, when lowered into the dilution tank 110 under the control of the device control unit 175, introduces the diluted sample or internal standard in the dilution tank 110 into the flow paths of the ion-selective electrodes 101 to 103. A sipper syringe pump 133 is used to introduce the reference electrode solution from a reference electrode solution bottle 161 into the flow path of the reference electrode 104. During this time, the vacuum suction nozzle 106 descends under the control of the device control unit 175 , sucks up the diluted specimen or internal standard remaining in the dilution tank 110 , and discharges it into the waste liquid tank 111 .

[0039] <Detailed Operation of Mechanical Parts> A detailed description will be given of the operation of the mechanical parts when introducing a liquid into the flow path from ion selective electrodes 101 to 103. When introducing a liquid from dilution tank 110 into the flow path from ion selective electrodes 101 to 103, device control unit 175 closes solenoid valves 121 and 125, opens pinch valve 105 and solenoid valve 122, lowers sipper nozzle 107 into the dilution tank, and pulls sipper syringe pump 133.

[0040] Next, when introducing the reference electrode solution into the flow path of the reference electrode 104, the device control unit 175 opens the solenoid valve 121, closes the pinch valve 105, and pulls the sipper syringe pump 133. This allows the reference electrode solution to be introduced from the reference electrode solution bottle 161 into the flow path of the reference electrode 104. Furthermore, the device control unit 175 closes the solenoid valve 122, opens the solenoid valve 125, and pushes the sipper syringe pump 133 to discharge the solution accumulated in the sipper syringe pump 133.

[0041] The reference electrode solution introduced into the flow path of the reference electrode 104 and the solution introduced into each of the ion selective electrodes 101 to 103 come into contact at the liquid junction 120. As a result, each of the ion selective electrodes 101 to 103 and the reference electrode 104 are electrically connected through the solution. At this time, the electromotive force (potential) between the reference electrode 104 and each of the ion selective electrodes 101 to 103 changes depending on the concentration of the ion to be measured in the solution introduced into the flow path of the ion selective electrodes 101 to 103, etc.

[0042] This potential information is acquired by the potential measurement unit 171. The concentration calculation unit 172 receives the potential measured at a stable timing suitable for concentration calculation from the potential measurement unit 171, and calculates the concentration of the ion to be measured. The output unit 174 displays the operating status of the device received from the device control unit 175 and the calculation results from the concentration calculation unit 172. The input unit 176 allows the operator to input sample information, various parameters, device operation commands, etc. Details of the calculation method will be described later.

[0043] <Device Start-Up Operation> FIG. 4 is a flowchart for explaining the operation of the electrolyte concentration measuring device 100 at the time of start-up.

[0044] (i) Overview of Start-Up Operations The operator starts up the electrolyte concentration measurement device 100, for example, by turning on the power switch (S201). Next, the operator installs (mounts) the ion selective electrodes 101 to 103 in the device 100 (S202) and then installs a reagent bottle in the device 100 (S203). In response to the operator's instructions, the device control unit 175 performs reagent priming (replenishing and filling each syringe pump and flow path with new reagent) (S204). Also, in response to the operator's instructions, the device control unit 175 continuously measures the internal standard solution to confirm that the electrode potential is stable (S205). Furthermore, to obtain a calibration curve for the ion selective electrodes 101 to 103, the device control unit 175 measures two types of standard solutions of known concentrations and calculates the slope (S206). Next, the device control unit 175 calculates the concentration of the internal standard solution (S207).

[0045] (ii) Details of S206 and S207 The specific operations of S206 and S207 are now described. The device control unit 175 dispenses the known low-concentration standard solution into the dilution tank 110 using a dispensing nozzle (not shown), and then uses the dilution syringe pump 132 to dispense the dilution solution in the dilution tank. This dilution involves diluting the known low-concentration standard solution at a preset ratio D. The device control unit 175 then aspirates the diluted known low-concentration standard solution from the dilution tank through the sipper nozzle 107 and introduces it into the flow paths of the ion selective electrodes 101 to 103. The device control unit 175 then introduces the reference electrode solution from the reference electrode solution bottle 161 into the flow path of the reference electrode 104. At this time, the reference electrode solution and the diluted known low-concentration standard solution come into contact at the liquid junction 120.

[0046] The device control unit 175 uses the potential measurement unit 171 to measure the electromotive forces between the ion selective electrodes 101 to 103 and the reference electrode 104 after the diluted standard solution has been introduced into the electrode flow path and while the solution is still. Meanwhile, the device control unit 175 controls the vacuum suction nozzle 106 to suck up the remaining solution in the dilution tank 110, and then dispenses the internal standard solution from the internal standard solution bottle 141 into the dilution tank 110. Furthermore, the device control unit 175 sucks the internal standard solution from the dilution tank 110 through the sipper nozzle 107, filling the flow paths of the ion selective electrodes 101 to 103 with the internal standard solution, and introduces the reference electrode solution from the reference electrode solution bottle 161 into the flow path of the reference electrode 104. The device control unit 175 then controls the potential measurement unit 171 to measure the electromotive forces of the electrodes after the internal standard solution has been introduced into the electrode flow path and while the solution is still. During this time, the device control unit 175 sucks up the remaining liquid in the dilution tank 110 using the vacuum suction nozzle 106, and then dispenses the known high-concentration standard liquid into the dilution tank 110 using a dispensing nozzle (not shown). Thereafter, the device control unit 175 uses the dilution liquid syringe pump 132 to dispense the dilution liquid in the dilution liquid bottle 151 into the dilution tank 110, diluting the known high-concentration standard liquid at the set ratio D.

[0047] The device control unit 175 aspirates the diluted known high-concentration standard solution in the dilution tank 110 through the sipper nozzle 107 and introduces it into the flow paths of the ion selective electrodes 101 to 103. The device control unit 175 then introduces the reference electrode solution from the reference electrode solution bottle 161 into the flow path of the reference electrode 104. The reference electrode solution and the diluted known high-concentration standard solution come into contact at the liquid junction 120. The device control unit 175 then controls the potential measurement unit 171 to measure the electromotive forces between the ion selective electrodes 101 to 103 and the reference electrode 104 while the solution is stationary after the diluted standard solution has been introduced into the electrode flow path. Meanwhile, the device control unit 175 sucks up the remaining solution in the dilution tank using the vacuum suction nozzle, and then dispenses the internal standard solution from the internal standard solution bottle 141 into the dilution tank.

[0048] The device control unit 175 sucks the internal standard solution from the dilution tank 110 through the sipper nozzle 107, fills the flow paths of the ion selective electrodes 101 to 103 with the internal standard solution, and introduces the reference electrode solution from the reference electrode solution bottle 161 into the flow path of the reference electrode 104. The device control unit 175 then controls the potential measurement unit 171 to measure the electromotive force of each electrode after the internal standard solution has been introduced into the electrode flow path while the solution is stationary. The device control unit 175 also sucks up the remaining solution in the dilution tank 110 using a vacuum suction nozzle.

[0049] As described above, the electromotive forces of the three types of solutions, namely, the low-concentration standard solution, the high-concentration standard solution, and the internal standard solution, are obtained by the potential measurement unit 171. The device control unit 175 controls the concentration calculation unit 172 and calculates the slope sensitivity SL corresponding to the calibration curve from the electromotive forces (EMF) received from the potential measurement unit 171 using the following formula:

[0050] (ii-1) Slope sensitivity SL = (EMFH - EMFL) / (LogCH - LogCL) (1) SL: Slope sensitivity EMFH: Measured electromotive force of known high concentration standard solution EMFL: Measured electromotive force of known low concentration standard solution CH: Known concentration value of high concentration standard solution CL: Known concentration value of low concentration standard solution

[0051] The above operation is called calibration. The slope sensitivity SL corresponds to 2.303 × (RT / zF) in the Nernst equation (2) below. While it can be calculated from the temperature and the valence of the ion to be measured, the electrolyte concentration measuring device 100 uses the above calibration to determine the electrode-specific slope sensitivity SL to further improve analytical accuracy. E = E0 + 2.303 × (RT / zF) × log(f × C) (2) where E0 is a constant potential determined by the measurement system, z is the valence of the ion to be measured, F is the Faraday constant, R is the gas constant, T is the absolute temperature, f is the activity coefficient, and C is the ion concentration.

[0052] (ii-2) Internal standard solution concentration Next, the internal standard solution concentration is calculated from the slope sensitivity and the electromotive force of the internal standard solution. CIS = CL × 10 ａ(3) a=(EMFIS-EMFL) / SL (4) where CIS is the concentration of the internal standard solution, and EMFIS is the electromotive force of the internal standard solution.

[0053] Although the specific calibration method has been described above, a different procedure may be used as long as two or more types of liquid with different ion concentrations are introduced into the flow path and the electromotive force is measured. Furthermore, a standard sample with a composition similar to that of a serum sample or urine sample may be measured, and the calibration results may be further corrected.

[0054] <Continuous Analysis Operation> After calibration, the electrolyte concentration measuring device 100 performs analysis using serum, urine, etc. as a sample. Fig. 5 is a flowchart for explaining the operation of the electrolyte concentration measuring device 100 during continuous analysis.

[0055] (i) Overview of Continuous Analysis Operation When the device control unit 175 starts the measurement operation (S301), it dispenses the internal standard solution from the internal standard solution bottle 141 into the dilution tank 110. Next, the device control unit 175 aspirates the internal standard solution from the dilution tank 110 through the sipper nozzle 107, filling the flow paths of the ion-selective electrodes 101 to 103 with the internal standard solution, and introduces the reference electrode solution from the reference electrode solution bottle 161 into the flow path of the reference electrode 104 (S302). The device control unit 175 then controls the potential measurement unit 171 to measure the electromotive force of each electrode (S303). During this time, the device control unit 175 sucks up the solution remaining in the dilution tank 110 using the vacuum suction nozzle 106, and then dispenses the sample into the dilution tank 110 using a dispensing nozzle (not shown). Thereafter, the device control unit 175 dispenses the diluent from the diluent bottle 151 into the dilution tank using the diluent syringe pump 132, diluting the sample at the set ratio D. Furthermore, the device control unit 175 aspirates the diluted specimen (sample) in the dilution tank 110 through the sipper nozzle 107, filling the flow paths of the ion selective electrodes 101 to 103, and introduces the reference electrode solution from the reference electrode solution bottle 161 into the flow path of the reference electrode 104 (S304). The device control unit 175 then controls the potential measurement unit 171 to measure the electromotive force of each electrode (S305). The device control unit 175 also sucks up the solution remaining in the dilution tank 110 using a vacuum suction nozzle.

[0056] Next, the device control unit 175 receives the potential value (electromotive force) from the potential measurement unit 171 (S306), and controls the concentration calculation unit 172 to calculate the concentration of the specimen from the above slope sensitivity and the internal standard solution concentration using the following formula (S308).

[0057] (ii) Concentration of the sample C Ｓ = CIS x 10 ｂ (5) b=(EMFIS-EMFS) / SL (6) where CS is the analyte concentration, and EMFS is the measured electromotive force of the analyte. Note that this technology can be used even if the device configuration, the structure of the reference electrode, the measurement sequence, the concentration calculation method, etc. are different from those of this embodiment.

[0058] (2) Second Embodiment Similar to the first embodiment, the second embodiment relates to a flow-type chloride ion-selective electrode shown in FIGS. 1A to 1C.

[0059] <Configuration Example of Ion-Sensitive Membrane 17> Fig. 6 is a schematic enlarged view of the portion enclosed by the dotted line rectangle 17-1 in Fig. 1C, showing the layer structure of the ion-sensitive membrane 17, which is characteristic of this embodiment. As shown in Fig. 6, the ion-sensitive membrane 17 according to the second embodiment includes an anion-exchange membrane 1, MPDA condensation layers 2 provided on both the top and bottom of the anion-exchange membrane 1, and an inactive layer 5 provided on the surface of the MPDA condensation layer 2 that comes into contact with the sample solution.

[0060] (Electrode Manufacturing Procedure) (i) The ion-sensitive membrane 17 is based on the anion-exchange membrane 1 having cations immobilized at a high density. First, the anion-exchange membrane 1 is immersed in a solution in which metaphenylenediamine is dissolved in a solvent.

[0061] (ii) Subsequently, the anion exchange membrane 1 is immersed in a mixed solution of formaldehyde and an inorganic acid to form a condensate of metaphenylenediamine (MPDA) and formaldehyde on the ion exchange membrane. This condensation layer is called an MPDA condensation layer 2.

[0062] (iii) A solution of PVC dissolved in tetrahydrofuran (THF), a low-boiling point solvent, is applied to the surface of the ion exchange membrane 1 on which the MPDA condensation layer 2 is formed, which surface comes into contact with the sample solution, and the THF is evaporated to form a thin polymer layer (inactive layer). (iv) Then, the anion exchange membrane 1 is adhered to the electrode housing 11 so as to close the opening provided in the electrode housing 11.

[0063] (v) Then, the electrode housing 11 is filled with the internal gel 16, and the lid 18 is welded to the electrode housing 11, and the internal electrode 13 is fixed so as to contact the internal gel 16. Note that, in order to suppress evaporation of water from the internal gel 16, the surface of the ion-sensitive membrane 17 on the side opposite the flow path may be coated with a resin or the like.

[0064] (Configuration example of anion exchange membrane 1) As in the first embodiment, the anion exchange membrane 1 constituting the ion-sensitive membrane 17 according to the second embodiment can also be a highly cross-linked polystyrene-based membrane having quaternary ammonium ions as anion exchange groups, and reinforced with a woven fabric of PVC (polyvinyl chloride) yarn.

[0065] However, the present invention is not limited to this membrane, and the ion exchange group may be a primary to tertiary amino group, the base material may be a hydrocarbon resin such as polyolefin or a fluorine-based resin instead of a styrene-based resin, etc. Furthermore, the reinforcing material may be other materials such as other polymer fibers or glass fibers, and the membrane may not have a reinforcing material.

[0066] Furthermore, the counter ions contained in the anion exchange membrane 1 are preferably the same type of ions as the ions to be measured, but may be other anions. Furthermore, the effects of the technology disclosed herein can be achieved even if the material is not that used for general ion exchange membranes, as long as the membrane has a high density of fixed charges. Here, high density means a charge density of approximately 0.1 to 10 mmol / g.

[0067] <Configuration Example of Inactive Layer 5> Although the constituent material of the inactive layer 5 is itself insulating, it is formed to be appropriately thin, so that it can create a state in which ion permeation is not completely insulated. In order to obtain the effect of suppressing the ion exchange reaction, a layer thickness of 0.10 μm or more is required. Furthermore, since ion exchange is completely blocked, there will be no ion response, so a portion of the layer thickness of 10 μm or less is required.

[0068] As described above, the structure of the ion-sensitive membrane 17 according to the second embodiment is a structure in which the MPDA condensation layer 2 is added to the ion-sensitive membrane 17 according to the first embodiment. The MPDA condensation layer 2 serves to improve the ion selectivity of the ion-sensitive membrane 17 itself. In the second embodiment, too, by forming the inactive layer 5 on the MPDA condensation layer 2, the ion exchange reaction can be suppressed, and the electrode characteristics during practical use can be brought closer to the ion selectivity inherent to the membrane. Specific electrode performance will be described later. The materials used for the ion-exchange membrane 1 and the inactive layer 5 can be selected from a variety of materials, as in the first embodiment described above.

[0069] In this way, even if a treatment for improving ion selectivity (forming an MPDA condensation layer 2) is applied to an ion exchange membrane 1 having a high density of fixed charges, the technical effects of the technology of the present disclosure can be expected as long as the inactive layer 5 is formed. In addition, the technology of the present disclosure can also be applied to other anion-selective electrodes and cation-selective electrodes.

[0070] <Configuration Example of Electrolyte Concentration Measuring Device> The ion selective electrode 10 according to the second embodiment can be used in the above-described electrolyte concentration measuring device 100 (see FIG. 3), similar to the ion selective electrode 10 according to the first embodiment.

[0071] (3) Third Embodiment The third embodiment relates to a stick-type ion-selective electrode. Fig. 9 is a diagram showing an example of the cross-sectional configuration of a stick-type ion-selective electrode 20 according to the third embodiment.

[0072] <Configuration Example of Stick-Type Ion-Selective Electrode> The stick-type ion-selective electrode 20 includes an electrode housing 22 with an opening (the opening at the bottom in Figure 9). The stick-type ion-selective electrode 20 includes an ion-sensitive membrane 17 disposed so as to cover the opening. The surface of the ion-sensitive membrane 17 that comes into contact with the sample solution is coated with an inert layer 26. The electrode housing 22 further includes an internal gel (internal liquid) 23 containing an electrolyte that fills the interior of the electrode housing 22. An internal electrode 24 is disposed so as to come into contact with the internal liquid 23, and a lid 25 is attached to confine the internal liquid 23 within the electrode housing 22. Note that by mounting the ion-selective electrode 20 in an electrolyte concentration measuring device 100 (see Figure 3) and connecting the internal electrode 24 to wiring on the device 100, the potential generated in response to the concentration of the target ions contained in the sample solution can be measured, and the concentration of the target ions can be analyzed.

[0073] <Electrode Manufacturing Procedure> A method for manufacturing the stick-type ion selective electrode 20 according to this embodiment will be described below.

[0074] (i) First, the ion exchange membrane 21 having a fixed charge is coated with the inert layer 26. At this time, the entire surface may be coated, or only the surface that comes into contact with the sample may be coated.

[0075] (ii) The electrode casing 22 and the ion exchange membrane 21 coated with the inert layer 26 are bonded together so as to close the opening provided in the electrode casing 22 .

[0076] (iii) Then, the electrode housing 22 is filled with an internal gel (internal liquid) 23 , the lid 25 is attached, and the internal electrode 24 is placed so as to come into contact with the internal gel 23 .

[0077] The ion-exchange membrane 21 may be previously subjected to a treatment for improving ion selectivity (for example, forming an MPDA condensation layer 2) as described in the second embodiment. The layer structure of the ion-sensitive membrane 17 according to this embodiment is the same as that of the first and second embodiments, and therefore has equivalent characteristics as the ion-sensitive membrane 17 in terms of slope sensitivity, ion selectivity, electrical resistance, service life, potential stability, and the like.

[0078] Such a stick-type ion-selective electrode 20 is typically immersed together with a reference electrode in a container containing a sample solution, and the sample solution in the container is stirred with a stirrer while the potential is measured. The structure of this embodiment suppresses the ion exchange reaction between the ion exchange membrane and the sample solution compared to conventional ion-exchange membrane-based ion-selective electrodes, thereby enabling practical ion selectivity close to that of the ion-sensitive membrane itself and enabling measurements that are less dependent on the flow rate of the sample solution. Other aspects, such as the material composition, functions, and effects, are the same as those of the first and second embodiments.

[0079] (4) Comparative Examples <Comparative Example 1> (i) Example Configuration of Ion-Selective Electrode A schematic front view of the flow-type ion-selective electrode of Comparative Example 1 is shown in FIG. 1A, as in the first embodiment. FIG. 1B is a diagram showing an example of the A-A' cross-sectional configuration of FIG. 1A. FIG. 1C is a diagram showing an example of the B-B' cross-sectional configuration. The flow-type ion-selective electrode of Comparative Example 1 has a flow path 12 penetrating an electrode housing 11, through which a sample liquid to be measured passes. An ion-sensitive membrane is provided so as to contact the sample liquid, and an internal gel 16 containing an electrolyte is further provided so as to fill the electrode housing 11. An internal electrode 13 is provided so as to contact the internal gel 16, and a lid 18 is attached to confine the internal gel within the electrode housing. In addition, a gasket 15 is provided near the inlet / outlet of the flow path 12 of the electrode housing so as to allow connection to the flow path of a device or another electrode.

[0080] 7 is an enlarged view of the dotted rectangle 17-1 in FIG. 1C, showing the layer structure of the ion-sensitive membrane of this comparative example. The ion-sensitive membrane of comparative example 1 is composed of an anion-exchange membrane 1. Unlike the ion-sensitive membranes 17 of the first and second embodiments, the ion-sensitive membrane does not include an inert layer 5.

[0081] (ii) Procedure for manufacturing an ion-selective electrode (ii-1) First, the anion exchange membrane 1 having immobilized cations is welded to the electrode housing 11 using tetrahydrofuran (THF), a low-boiling point solvent, so as to block the opening provided in the electrode housing 11.

[0082] (ii-2) Then, the electrode housing 11 is filled with the internal gel 16 , the lid 18 is welded, and the internal electrode 13 is fixed so as to contact the internal gel 16 .

[0083] In this Comparative Example 1, the anion exchange membrane 1 is a highly cross-linked polystyrene membrane having quaternary ammonium groups as anion exchange groups, and is reinforced with a woven PVC (polyvinyl chloride) yarn fabric. The ion-selective electrode manufactured in this manner has a structure in which the ion exchange membrane 1 is directly exposed to the sample solution. Specific electrode performance will be described later.

[0084] Comparative Example 2, like that described in Comparative Example 1, relates to the flow-type ion-selective electrode shown in Figures 1A to 1C. Figure 8 is an enlarged view of the portion enclosed by the dotted rectangle 17-1 in Figure 1C, and shows the layer structure of the ion-sensitive membrane of Comparative Example 2.

[0085] (i) Procedure for manufacturing an ion-selective electrode (i-1) First, an anion exchange membrane 1 having immobilized cations is immersed in a solution in which metaphenylenediamine is dissolved in a solvent, and then immersed in a mixed solution of formaldehyde and an inorganic acid, thereby forming a condensate of metaphenylenediamine (MPDA) and formaldehyde on the anion exchange membrane 1.

[0086] (i-2) The ion exchange membrane 1 on which the MPDA condensation layer 2 is formed is welded to the electrode case 11 using THF, which is a low boiling point solvent, so as to close the opening provided in the electrode case 11.

[0087] (i-3) Then, the inside of the electrode housing 11 is filled with the internal gel 16, and the lid 18 is welded and fixed so that the internal electrode is in contact with the internal gel 16.

[0088] In this comparative example 2, the anion exchange membrane 1 is a highly cross-linked polystyrene-based membrane having quaternary ammonium groups as anion exchange groups, and is reinforced with a woven fabric made of PVC (polyvinyl chloride) yarn.

[0089] The ion-selective electrode manufactured by this method has a structure in which the MPDA-condensed ion-exchange membrane 1 comes into contact with the sample solution. Specific electrode performance will be described later.

[0090] (5) Measurement Examples (Examples) <Measurement Example 1> (i) Measurement Results The response behavior of the ion-selective electrode 10 having the structure shown in the first embodiment, in which PVC is used as the material for the inactive layer 5, and the electrode of Comparative Example 1 was investigated with respect to aqueous solutions containing various concentrations and types of ions. Fig. 10 is a diagram showing the comparison results of the response behavior. In the graph of Fig. 10, the horizontal axis represents time, and the vertical axis represents the acquired potential (EMF: in the case of an anion-selective electrode, the slope sensitivity is negative, so a smaller value indicates a higher sensitivity).

[0091] The black dots on the thick line at the top of the graph indicate the timing when each sample solution was introduced. The solution was kept stationary except when the solution was introduced. As a result, even with the electrode of Comparative Example 1, the potential when the solution was stationary was stable over time for all of the NaCl aqueous solutions of different concentrations shown in Figure 10 (a) to (c).

[0092] However, in (d) of FIG. 10, 10 mM NaHCO ３ For NaHCO3, the potential dropped sharply immediately after the solution came to rest, and the change gradually became more gradual. ３ When the aqueous solution was introduced, it started from almost the same potential as the first time and drew a similar curve. ３ When 10 mM NaBr was introduced, the potential also changed in the negative direction. On the other hand, in Figure 10(f), when 10 mM NaBr was introduced, the potential rose sharply immediately after the solution came to rest, and the change gradually became more gradual. In Figure 10(g), when 10 mM NaSCN was introduced, an even more significant potential change was observed. The phenomenon was reproduced when the same solution was introduced again. Finally, in Figure 10(h), when 10 mM NaCl was introduced, the potential was approximately the same as in Figure 10(b).

[0093] In contrast to this, the ion selective electrode 10 having the structure according to the first embodiment exhibited a relatively stable potential for all the solutions ((a) to (h) in FIG. 10).

[0094] (ii) Why the inactive layer 5 can prevent the effects of interfering ions Here, we will explain the mechanism by which the potential changes over time when a sample solution containing interfering ions is measured in the ion-selective electrode having the structure according to Comparative Example 1 (see Figure 7), while this phenomenon does not occur in the ion-selective electrode 10 having the structure according to the first embodiment (see Figure 2).

[0095] 11A is a diagram showing a schematic diagram of the ion composition inside the ion-sensitive membrane and the sample solution of Comparative Example 1. In Comparative Example 1, cations (positive ions) immobilized in the ion-exchange membrane 1 of the ion-sensitive membrane are present at a high concentration, and chloride ions (Cl) are present as counter ions. － ) is present. Therefore, the interfering ion J － When the membrane comes into contact with a sample solution containing － and Cl in the film － With the passage of time after the liquid has come to rest, the state changes from state (a) in FIG. 11A to state (b).

[0096] For example, J － is bicarbonate ion (HCO ３ － ), the ion-sensitive membrane is HCO ３ － From Cl － Therefore, the HCO ３ － is Cl － When the ion concentration is changed to 100 mM NaCl, the ion-sensitive membrane senses (detects) an increase in the ion concentration of the sample solution. The anion-selective electrode has a negative slope sensitivity (the potential difference when the ion concentration to be measured is increased by one digit in Figure 10: for example, the theoretical slope sensitivity when the ion concentration to be measured is changed from 10 mM NaCl to 100 mM NaCl is about -59 mV / decade at room temperature). － is Cl －As the exchange reaction to HCO progresses, the potential decreases (see (d) and (e) in Figure 10). When the same sample solution is introduced again, the sample solution is refreshed and the same phenomenon occurs again. Note that HCO is also present on the ion exchange membrane 1 side. ３ － However, Cl does not enter the ion exchange membrane 1. － Since the particles are present at high density, it is thought that the effect on membrane performance is small.

[0097] For example, Cl － Higher selectivity of Br － and SCN － When a sample solution containing hydrophobic ions such as J － Br － and SCN － In the case of － and SCN － is Cl － When the electrons are exchanged with the electrons, the potential changes in the opposite direction, increasing (see (f) and (g) in FIG. 10).

[0098] On the other hand, in the case of the ion-selective electrode 10 including the inert layer 5 (in the first and second embodiments), the phenomenon shown in Fig. 11A can be prevented. Fig. 11B is a diagram schematically showing the ion composition inside the ion-sensitive membrane 17 and the sample solution in the case of the ion-selective electrode 10 including the inert layer 5. Because the surface of the ion-sensitive membrane 17 is covered with the inert layer 5, the ion exchange reaction between the ion-exchange membrane 17 and the sample solution is suppressed, and the potential change due to the ion exchange reaction as in Comparative Example 1 is less likely to occur.

[0099] FIG. 12 shows the slope and chloride ion (Cl) potentials obtained from the potential values ​​at relatively stable timings after the second introduction of each sample solution in FIG. 10. －7 shows the results of calculating the selectivity coefficients of each interfering ion for each of the interfering ions (values ​​indicating the degree of response of the interfering ions when chloride ions are set to 1). The numbers in parentheses indicate the selectivity calculation results at an ion concentration of 100 mM. The slope sensitivity was almost the same for both the ion selective electrode 10 having the structure shown in FIG. 2 (first embodiment) and the ion selective electrode having the structure shown in FIG. 7 (comparative example 1). The selectivity coefficient was higher for HCO 3 , a hydrophilic ion, in the structure according to the first embodiment compared to comparative example 1. ３ － The selectivity of Br is low and the hydrophobic ion － and SCN － This is thought to be because, in Comparative Example 1, the ion composition of the sample solution near the membrane changes due to the ion exchange reaction, so that a less drastic value of the selectivity coefficient is obtained in the actual measurement, whereas, in the structure according to the first embodiment, the inactive layer can suppress the ion exchange reaction, so that a value close to the original selectivity coefficient of the ion-sensitive membrane 17 can be measured. ３ － The selectivity values ​​were close to each other. This is thought to be because the high ion concentration in the solution made the effect of ion flux relatively small, making it difficult to see the difference between the presence and absence of the inert layer.

[0100] In Comparative Example 1, SCN － The selectivity coefficient was less than 1 for SCN. － Possible reasons for this include a change in membrane characteristics due to the intrusion of ions into the ion exchange membrane 1, or the influence of the diffusion potential within the ion exchange membrane 1.

[0101] As described above, unlike a general liquid membrane-type ion-sensitive membrane with a low density of fixed charges, a membrane with a high density of fixed charges such as the ion exchange membrane 1 according to this embodiment undergoes a rapid ion exchange reaction with the liquid. By covering the surface of the ion exchange membrane 1 with the inert layer 5 as in the embodiment of the present disclosure, this ion exchange reaction is suppressed, and it becomes possible to approach the original ion selectivity of the ion-sensitive membrane 17.

[0102] Measurement Example 2 The ion selective electrode having the structure according to Comparative Example 1 (see FIG. 7) and the ion selective electrode having the structure according to the first embodiment (see FIG. 2) were measured to determine the chlorine ion (Cl － ) to bicarbonate ion (HCO ３ － ) selectivity coefficient was measured. Figure 13 shows the measurement results. The bicarbonate ion selectivity coefficient was evaluated using the so-called mixed solution method, which uses a sample solution with interfering ions added to a standard solution. For a chloride ion selective electrode, a small selectivity coefficient for bicarbonate ion, which is an interfering ion, is desirable. A high-throughput automatic analyzer was used as the measurement device. This device performs analysis by diluting the sample.

[0103] In Fig. 13, No. 1 shows the bicarbonate ion selectivity coefficient of an electrode equipped with an untreated ion exchange membrane 1 (electrode structure of Comparative Example 1). No. 2 shows the bicarbonate ion selectivity coefficient of an electrode equipped with a membrane in which only THF (containing no polymer) was applied to the surface of the ion exchange membrane 1 and dried (equivalent to the electrode structure of Comparative Example 1).

[0104] Nos. 3 to 9 show the bicarbonate ion selectivity coefficients of electrodes (structure of the first embodiment) equipped with membranes in which THF solutions of PVC, Ethylene / vinyl acetate copolymer, Poly(vinyl formal), PVC+DOA, Ethylene / vinyl acetate copolymer+DOA, Poly(ethyl methacrylate)+DOA, and Poly(vinyl acetate)+DOA were dissolved, and then the membrane surface was coated and dried.

[0105] 13 , the bicarbonate ion selectivity coefficients of electrodes No. 3 to No. 9, which have the structure of the first embodiment, are smaller than those of electrodes No. 1 and No. 2, which have the structure of Comparative Example 1, demonstrating improved performance. Thus, by forming the inactive layer 5 on the surface of the ion-exchange membrane 1, it is possible to achieve ion selectivity close to that inherent to the ion-sensitive membrane 17, regardless of the type of material of the inactive layer 5.

[0106] Furthermore, although not shown, it has been confirmed that when the ion-sensitive membrane 17 of the structure of the first embodiment is inverted so that the surface coated with the inactive layer 5 faces the inner gel 16, the ion-selective electrode 10 has a significantly larger bicarbonate ion selectivity coefficient than an electrode in which the surface coated with the inactive layer 5 faces the sample solution. Therefore, it can be said that it is effective to form the inactive layer 5 between the ion-exchange membrane 1 and the sample solution.

[0107] Measurement Example 3 The ion selective electrode having the structure according to Comparative Example 2 (see FIG. 8) and the ion selective electrode having the structure according to the second embodiment (see FIG. 6) were measured for chloride ions (Cl － ) to bicarbonate ion (HCO ３ － The selectivity coefficients for the bicarbonate ion were measured. Figure 14 shows the measurement results. The bicarbonate ion selectivity coefficient was evaluated using the so-called mixed solution method, in which a sample solution containing interfering ions was used in a standard solution. For a chloride ion-selective electrode, a small selectivity coefficient for bicarbonate ion, an interfering ion, is preferable. A high-throughput automatic analyzer was used as the measurement device. This device performs analysis by diluting the sample. PVC was used as the material for the inert layer 5 of the structure according to the second embodiment, and five electrodes were fabricated with average layer thicknesses of 0.1 μm, 1 μm, and 10 μm. Figure 14 shows the average values ​​of the bicarbonate ion selectivity coefficients in a bar graph, with error bars indicating the maximum and minimum values.

[0108] In Figure 14, "Blank" represents the results corresponding to the ion-selective electrode having the structure according to Comparative Example 2. That is, this is a membrane in which a condensation layer 2 of MPDA and formaldehyde is formed on an anion-exchange membrane 1, and no inert layer is formed. The bicarbonate ion selectivity coefficient of this ion-selective electrode was approximately 0.19. An ion-sensitive membrane 17 (structure according to the second embodiment) in which an inert layer 5 having an average thickness of 0.1 µm was formed on this ion-sensitive membrane did not show a significant difference in bicarbonate ion selectivity coefficient compared to an ion-sensitive membrane not covered with the inert layer 5 (corresponding to Comparative Example 2).

[0109] On the other hand, the ion-sensitive membrane 17 in which the inactive layer 5 was formed with an average thickness of 1 μm exhibited a greatly improved bicarbonate ion selectivity coefficient of approximately 0.09. Furthermore, the ion-sensitive membrane 17 in which the thickness of the inactive layer 5 was increased to 10 μm did not exhibit a proper ion response because the inactive layer 5 was too thick, and the slope sensitivity exhibited an irregular value.

[0110] From the above measurement results, it is considered that a thickness of 0.1 μm or less is insufficient for the inactive layer 5 to perform its function of suppressing the ion exchange reaction, and that a thickness of 10 μm or more makes the inactive layer 5 too thick to exhibit the ion response characteristics of the ion exchange membrane 1. Therefore, it is found that the thickness of the inactive layer 5 should be between 0.1 and 10 μm to improve ion selectivity.

[0111] Although not shown, the ion-sensitive membrane 17 having the inactive layer 5 formed with an average thickness of 1 μm still exhibited the effect of the inactive layer 5 even after storage, and maintained a lower selectivity coefficient than the ion-sensitive membrane (comparative example) not covered with the inactive layer 5. Thus, the inactive layer 5 can be effective even after long-term storage.

[0112] From the above results, the effect of the present disclosure of improving ion selectivity was confirmed by forming an inactive layer 5 on the ion-sensitive membrane 17 that has been treated to improve selectivity compared to the ion exchange membrane 1.

[0113] (6) Summary The ion-sensitive membrane in the ion-selective electrode according to each embodiment has at least a part of its first surface in contact with the sample liquid, and at least a part of its second surface, which is different from the first surface (opposite the first surface), in contact with the internal gel (internal liquid). The first surface of the ion-sensitive membrane is coated with an inert layer that suppresses ion exchange reactions between the ion-sensitive membrane and the sample liquid. Here, the ions to be measured contained in the sample liquid are various anions and various cations. For example, Br － , I － , C.N. － , Cd ２＋ , Cu ２＋ , Ag ＋ , S ２－ , F － , K. ＋ , Ca２＋ , NO ３ － , N.H. ４ ＋ , Na ＋ The following can be measured. In this way, in an ion-selective electrode based on an ion-exchange membrane (ion-exchange resin) 1 having a high density of fixed charges, the addition of a structure (inactive layer) that can be manufactured using a simple process can improve ion selectivity and stability over time. An ion-selective electrode having such a structure is also suitable for automatic analyzers that perform continuous measurements at high throughput, and can achieve further improvements in the analytical accuracy and reliability of ion concentration measurements.

[0114] The ion-selective electrode is based on an ion-exchange membrane (ion-exchange resin) 1 having a high density of fixed charges, and in this case, the charge density of the fixed charges can be 0.1 mmol / g or more.

[0115] On the other hand, when the ion concentration in the sample solution is low, even a slight ion exchange phenomenon between the ion exchange membrane and the sample solution affects the measured value, and this also applies when the charge density of the ion-sensitive membrane is not high as described above but is moderate, such as in the case of a liquid membrane-type ion-sensitive membrane. However, the effects of the present invention can be achieved even in such a system by providing an inert layer.

[0116] The inert layer can be made of a material that is not ion-responsive. Examples of the material that is not ion-responsive include insulating materials. Examples of the insulating material include polymeric materials (polymers containing carbon and hydrogen, and materials containing at least one of chlorine and oxygen). The charge density of the inert layer can be set to 0.001 mmol / g or less. Furthermore, the inert layer has a portion with a thickness of 0.10 μm or more and 10 μm or less. By setting the thickness of the inert layer within this range, it is possible to reliably achieve ion response while suppressing ion exchange reactions.

[0117] Furthermore, the ion-sensitive membrane may be composed of an ion-exchange membrane 1, a treatment layer (e.g., an MPDA condensation layer) 2 formed on both sides of the ion-exchange membrane 1 (the first side faces the sample, and the second side faces the internal liquid) to improve ion selectivity, and an inert layer 5 formed on the condensation layer on the first side (second embodiment). By doing so, the ion selectivity of the ion-sensitive membrane 17 itself can be further improved.

[0118] 1, 21 Ion exchange membrane 2 MPDA condensation layer 5, 26 Inactive layer 11, 22 Electrode housing 12 Flow path 13, 24 Internal electrode 15 Gasket 16, 23 Internal gel 17 Ion-sensitive membrane 18, 25 Lid 100 Electrolyte concentration measuring device 101 Chloride ion electrode 102 Potassium ion electrode 103 Sodium ion electrode 104 Reference electrode 105 Pinch valve 106 Vacuum suction nozzle 107 Sipper nozzle 108 Dilution solution supply nozzle 109 Internal standard solution supply nozzle 110 Dilution tank 111 Waste tank 112 Vacuum pump 120 Liquid junction 121, 122, 123, 124, 125, 126, 127 Solenoid valve 131 Internal standard solution syringe pump 132 Diluent syringe pump 133 Sipper syringe pump 141 Internal standard solution bottle 151 Diluent bottle 161 Reference electrode solution bottle 171 Potential measurement section 172 Concentration calculation section 174 Output section 175 Device control section 176 Input section

Claims

1. An ion selective electrode for measuring a target ion contained in a sample liquid, An electrode housing that contains an internal liquid; an internal electrode having a portion in contact with the internal liquid; an ion-sensitive membrane that separates the sample liquid from the internal liquid; When the sample liquid side of the ion-sensitive membrane is defined as a first surface and the internal liquid side is defined as a second surface, the first surface of the ion-sensitive membrane is coated with an inert layer that suppresses an ion exchange reaction between the ion-sensitive membrane and the sample liquid, When a target ion is measured with the ion-selective electrode, at least a part of the inactive layer covering the first surface of the ion-sensitive membrane is in contact with the sample liquid, and at least a part of the second surface of the ion-sensitive membrane is in contact with the internal liquid, The inactive layer is made of a material that is not ion-responsive; the inactive layer has a charge density of 0.001 mmol / g or less; With the first surface of the ion-sensitive membrane coated with the inert layer, an ion-selective electrode is used to measure the concentration of the target ion.

2. In claim 1, The ion-sensitive membrane has a charge density of 0.1 mmol / g or more.

3. In claim 1, The ion-sensitive membrane comprises an ion exchange resin.

4. In claim 3, An ion-selective electrode, wherein the ion-sensitive membrane has a treatment layer that improves ion selectivity at least in the portion of the first surface that comes into contact with the sample, and the inactive layer is formed on the treatment layer on the first surface side.

5. In claim 1, An ion-selective electrode, wherein the inactive layer is composed of an insulating material.

6. In claim 1, The inactive layer comprises a polymeric material.

7. In claim 6, The polymeric material is a polymer containing carbon and hydrogen, an ion-selective electrode.

8. In claim 6, The polymer material contains at least one of the elements chlorine and oxygen, forming an ion-selective electrode.

9. In claim 1, The inactive layer has a portion having a thickness of 0.10 μm or more and 10 μm or less.

10. In claim 1, An ion selective electrode, wherein the ion of interest is an anion.

11. In claim 10, An ion selective electrode, wherein the target ion is a chloride ion.

12. In claim 1, An ion-selective electrode, wherein the ion of interest is a cation.

13. An ion-selective electrode according to claim 1; a concentration calculation unit that calculates the concentration of the target ion based on information on the potential measured using the ion selective electrode; An electrolyte concentration measuring device comprising: