Method for electrolyte analysis and electrolyte analysis device

Abstract

To enable operation at the lowest possible cost while maintaining high accuracy and precision and having sufficient processing speed, even in a case where samples with high concentrations of target ions or samples containing interfering substances are randomly and continuously introduced.SOLUTION: An electrolyte analysis device executes a measurement cycle of electrolyte concentration of a sample in the order of measuring the electromotive force of a sample liquid (S), performing a cleaning process (W) as an optional process, and measuring the electromotive force of a standard liquid (B). The electrolyte analysis device measures the electrolyte concentration of the sample by using the difference between the electromotive force of the sample liquid and the electromotive force of the standard liquid.SELECTED DRAWING: Figure 3

Description

[Technical Field]

[0001] The present invention relates to an electrolyte analysis method for measuring the electrolyte concentration of a sample, and more particularly to an electrolyte analysis method and an electrolyte analyzer for measuring the concentration of electrolytes (Na: sodium ion, K: potassium ion, Cl: chloride ion) in the analysis of biological samples, water quality, food, etc. [Background technology]

[0002] Since the late 1980s, devices for measuring electrolyte concentrations using ion-selective electrodes have been developed. A variety of devices have been developed and used up to the present day. These devices are used for analyzing biological samples (e.g., urine, serum, plasma, whole blood, cerebrospinal fluid, etc.), as well as for analyzing water quality and food.

[0003] An electrolyte analyzer uses an ion-selective electrode and a reference electrode to measure the electromotive force of a sample and also that of a reference solution for comparison. Then, based on the measurement data for the sample and reference solution, the concentration of the electrolyte (the component to be measured) contained in the sample is determined. Alternatively, the electromotive force can be measured after diluting the sample or reference solution with a diluent. In this case, the sample and diluent are first stirred and mixed in a dilution container to prepare a diluted sample solution. The diluted sample solution is then introduced into a measurement unit consisting of an ion-selective electrode and a reference electrode, and the electromotive force corresponding to the electrolyte concentration of the sample is measured. The standard solution is then similarly diluted and introduced into the measurement unit, and the electromotive force of the diluted standard solution is measured. The electrolyte concentration of the sample is then calculated from the difference between the electromotive forces of the sample and the standard solution.

[0004] As mentioned above, electrolyte analyzers are used to analyze biological samples, water quality, food, and other samples. The electrolyte concentrations of these samples vary widely and are subject to significant individual variation. Furthermore, samples often contain substances that, in principle, interfere with electrolyte measurement. As a concrete example, Table 1 shows the electrolyte concentrations of samples fed into electrolyte analyzers at hospitals in Japan.

[0005] [Table 1]

[0006] Table 1 shows the measured values ​​of 50 human urine samples. For example, the chloride ion concentration of sample number 36 was 6.44 mEq / L, while that of sample number 42 was 261.65 mEq / L, meaning that the latter was approximately 40 times higher than the former. When samples are randomly added, there is a possibility that samples with such different concentrations will be measured one after the other.

[0007] Thus, when consecutively analyzing samples in which the concentration of analyte ions and the presence or absence of interfering substances are unknown, operations performed after the measurement of the previous sample can affect the measurement of the next sample. If the previous sample is not sufficiently washed away and remains in the flow path, it will be contaminated with the next sample, resulting in analysis results with reduced accuracy and precision. Therefore, the flow path must be thoroughly cleaned to eliminate any residual influence of the previous sample. However, cleaning has the disadvantage of lengthening the processing time required for each sample. In recent years, market demands have also led to a desire for improved processing speed (shortening processing time), and so innovations have been made to balance accuracy and precision with processing speed (see, for example, Patent Documents 1 and 2 below). [Prior art documents] [Patent documents]

[0008] [Patent Document 1] International Publication No. 2020 / 116410 [Patent Document 2] International Publication No. 2022 / 146570 Summary of the Invention [Problem to be solved by the invention]

[0009] For example, Patent Document 1 above describes a technique for reducing the influence of the previous sample on the measurement of subsequent samples. Specifically, this technique branches the subsequent analysis process depending on the potential of the reference solution (here, an internal standard solution) after the measurement of the previous sample, and adds washing as necessary. Furthermore, Patent Document 2 above describes a technique for shortening the entire measurement process by providing a flow path that passes through an ion-selective electrode and a bypass flow path, and performing parts of the dilution operation, analysis operation, and washing operation in parallel.

[0010] However, even with these methods, the problem of using large amounts of diluent and internal standard solutions remains. Reagents for electrolyte analyzers are almost always proprietary to each equipment manufacturer, and the amount of reagent required to process one sample directly affects the running costs of the equipment. Furthermore, the high-performance control units and special attachments to the flow paths required to carry out processes with many conditional branches contribute to the high price of the equipment.

[0011] Therefore, there has been a demand for an electrolyte analyzer that maintains high accuracy and precision, has a sufficient processing speed, and can be operated at a reasonable cost.

[0012] In view of the above problems, the object of the present invention is to maintain high accuracy and precision, have sufficient processing speed, and be able to operate at the lowest possible cost, even when samples with high concentrations of target ions or samples containing interfering substances are randomly and continuously added. [Means for solving the problem]

[0013] The means for solving the above problems are as follows.

[0014] The electrolyte analysis method of the present invention is characterized in that the measurement cycle for the electrolyte concentration of a sample is performed in the following order: measurement of the electromotive force of the sample solution, an optional cleaning step, and measurement of the electromotive force of the reference solution, and the electrolyte concentration of the sample is measured using the difference between the electromotive force of the sample solution and the electromotive force of the reference solution.

[0015] Furthermore, the electrolyte analysis method of the present invention is a method in which the measurement cycle of the electrolyte concentration of a sample is performed in the following order: measurement of the electromotive force of a reference solution, measurement of the electromotive force of the sample solution, an optional cleaning step, and measurement of the electromotive force of the reference solution; and the method calculates the electrolyte concentration of the sample using the difference between the electromotive force of the sample solution and the electromotive force of the reference solution after correction, which is calculated based on both the electromotive force of the reference solution measured before measuring the electromotive force of the sample solution and the electromotive force of the reference solution measured after measuring the electromotive force of the sample solution; the method is characterized in that the electromotive force of the reference solution after correction is calculated by "electromotive force of the reference solution measured before measuring the electromotive force of the sample solution × x + electromotive force of the reference solution measured after measuring the electromotive force of the sample solution × (1-x)", and x in the above formula is greater than 0 and less than or equal to 0.5.

[0016] The electrolyte analyzer of the present invention is characterized by including a control unit that executes a measurement cycle for the electrolyte concentration of a sample in the following order: measurement of the electromotive force of the sample liquid, an optional cleaning process, and measurement of the electromotive force of the reference liquid; and a measurement unit that measures the electrolyte concentration of the sample using the difference between the electromotive force of the sample liquid and the electromotive force of the reference liquid.

[0017] The electrolyte analyzer of the present invention also includes a control unit that executes a measurement cycle of the electrolyte concentration of a sample in the following order: measurement of the electromotive force of a reference solution, measurement of the electromotive force of the sample solution, an optional cleaning process, and measurement of the electromotive force of the reference solution; and a measurement unit that calculates the electrolyte concentration of the sample using the difference between the electromotive force of the sample solution and a corrected electromotive force of the reference solution, the difference being calculated based on both the electromotive force of the reference solution measured before measuring the electromotive force of the sample solution and the electromotive force of the reference solution measured after measuring the electromotive force of the sample solution, wherein the measurement unit calculates the corrected electromotive force of the reference solution by "electromotive force of the reference solution measured before measuring the electromotive force of the sample solution × x + electromotive force of the reference solution measured after measuring the electromotive force of the sample solution × (1-x)", where x in the above formula is greater than 0 and less than or equal to 0.5.

[0018] The electrolyte analyzer of the present invention is characterized by comprising a sample supply unit that supplies a sample to a dilution container, a dilution liquid supply unit that supplies a dilution liquid to the dilution container, a sample dilution unit that mixes the sample supplied to the dilution container with the dilution liquid to produce a diluted sample solution, and a measurement unit that is arranged downstream of the sample dilution unit and measures the concentration of an electrolyte, which is a component to be measured contained in the diluted sample solution. [Effects of the Invention]

[0019] The present invention can maintain high accuracy and precision, have sufficient processing speed, and can be operated at low cost, even when samples with high concentrations of target ions or samples containing interfering substances are randomly and continuously added. [Brief explanation of the drawings]

[0020] [Figure 1] FIG. 1 is a diagram showing an example of the configuration of an electrolyte analyzer according to an embodiment of the present invention. [Figure 2] FIG. 2 is a diagram showing an example of the configuration of the control unit of the electrolyte analyzer according to the embodiment of the present invention. [Figure 3] FIG. 3 is a comparative diagram showing an outline of the measurement process according to the prior art and the embodiment of the present invention. [Figure 4] FIG. 4 is a comparison diagram of the sequences of the electrolyte analyzer according to the prior art (Comparative Example 1) and Example 1 of the present invention. [Figure 5] FIG. 5 is a comparison diagram of the sequences of the electrolyte analyzer according to the prior art (Comparative Example 2) and Example 2 of the present invention. [Figure 6] FIG. 6 is a comparison diagram of the sequences of the electrolyte analyzer according to the prior art (Comparative Example 3) and Example 3 of the present invention. [Figure 7] FIG. 7 is a comparison diagram of the sequences of the electrolyte analyzer according to the prior art (Comparative Example 4) and Example 4 of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0021] The following describes in detail an embodiment of the present invention, but the present invention is not limited to this.

[0022] (Configuration of the electrolyte analyzer of the present invention) 1 is a diagram showing an example (schematic diagram) of the configuration of an electrolyte analyzer according to an embodiment of the present invention. Here, as one example, an electrolyte analyzer that uses a method in which a sample is diluted with a diluent and then analyzed (the so-called dilution method) is described, but in accordance with the principles of the present invention, the same can be applied to an analyzer that uses a method in which a sample is analyzed as is without being diluted with a diluent (the so-called direct method).

[0023] An electrolyte analyzer 100 according to an embodiment of the present invention comprises a sample supply unit 110, an internal standard solution supply unit 120, a measurement unit 150, and a control unit 200 (not shown in FIG. 1 but shown in FIG. 2). Although a diluent supply unit 130 and a dilution unit 140 are also shown in FIG. 1, these are optional components. In the case of a direct method apparatus, a sample injection port is provided instead of the dilution unit.

[0024] The sample supply unit 110 includes a movable crane 113 that can move up, down, left, and right in the figure, a sample dispensing nozzle 112 provided on the movable crane, and a cleaning solution 111. The internal standard solution supply unit 120 includes an internal standard solution 121 and a solenoid valve (for supplying internal standard solution) 127. An internal standard solution flow path 3 connects the outlet of the solenoid valve (for supplying dilution solution) 127 to the base of an internal standard solution outlet (nozzle) for discharging the internal standard solution 121 into a dilution container 141.

[0025] A sample container (not shown) for containing the sample to be measured is provided along the moving path of movable crane 113. By moving movable crane 113 and performing a suction operation, sample dispensing nozzle 112 dispenses a fixed amount of sample from the sample container. The dispensed sample is carried to dilution section 140 by the movement of movable crane 113, and dispensed into dilution container 141. Note that when the electrolyte analyzer of the present invention is used as a unit of an automatic analyzer, sample supply section 110 may be provided in the main body of the automatic analyzer, and is not necessarily required.

[0026] The diluent supply unit 130 is composed of a diluent 131 and a solenoid valve (for supplying diluent) 137. The liquid is delivered by a syringe pump 170 and solenoid valve (for supplying diluent) 137, which operate in response to instructions from the control unit 200. Examples of diluents that can be used include aqueous tris(hydroxymethyl)aminomethane solutions, aqueous monomethanolamine solutions, aqueous diethanolamine solutions, aqueous triethanolamine solutions, sulfuric acid, phosphate, borate buffer solutions, and Good's buffer solutions such as MOPS and HEPES. The composition of these solutions can be freely selected depending on the purpose.

[0027] A diluent flow path 4 connects the outlet of the solenoid valve (for diluent supply) 137 to the base of the diluent outlet (nozzle) for discharging the diluent into the diluent container 141. The material of the diluent flow path 4 may be selected from Teflon (registered trademark), silicone, glass, ceramic, stainless steel, corrosion-coated metal, etc., as long as it is practically durable against the components of the diluent. For ease of handling, it is appropriate to select a flexible resin for the piping portion of the diluent flow path 4 and a resin (e.g., polyvinyl chloride, acrylic resin, polycarbonate, polyethylene terephthalate, polybutylene terephthalate, polystyrene, AS resin, ABS resin, etc.) or glass for the diluent chamber.

[0028] The dilution unit 140 is composed of a dilution container 141, a stirrer (not shown), and a diluent outlet. The stirrer can be freely selected as long as it meets the purpose, such as a stirring blade or a magnetic stirrer. Considering the efficiency of rinsing the sample and ease of maintenance, a small magnetic stirrer is desirable (Figure 1 shows an example using a magnetic stirrer. The stirrer itself is located deep inside the wall of the dilution container and is therefore omitted in Figure 1. Reference numeral 142 denotes a stirrer bar located inside the dilution container). The material of the dilution container 141 can be selected appropriately, such as metal, glass, or resin. Among these, transparent resins (e.g., polyvinyl chloride, acrylic resin, polycarbonate, polyethylene terephthalate, polybutylene terephthalate, polystyrene, AS resin, ABS resin, etc.) are desirable from the standpoints of visibility and processability. In addition, if a magnetic stirrer is used as the stirrer, it is best to use a resin with high sliding properties (such as fluororesin or polyacetal) in the area where the stirrer moves.

[0029] As described above, the sample to be measured is dispensed into the dilution container 141 by the sample dispensing nozzle 112. The dilution liquid is injected into the dilution container 141 from the dilution liquid supply unit 130 via the dilution liquid flow path 4. These are mixed by a mixer disposed in the dilution container 141 to form a uniform diluted sample solution. The diluted sample solution is sent to the measurement unit 150 installed downstream.

[0030] The measurement unit 150 is composed of various ion-selective electrodes 151 to 153 and a reference electrode 154. Examples of the ion-selective electrodes include a sodium ion-selective electrode 153, a potassium ion-selective electrode 152, and a chlorine ion-selective electrode 151, as well as a calcium ion-selective electrode and a magnesium ion-selective electrode. Various ion-selective electrodes can be selected depending on the purpose of the analysis. Note that multiple types of ion sensors may be combined and used simultaneously. Furthermore, sensors such as a temperature sensor and a pressure sensor may be added to obtain information other than the analysis of electrolyte concentration.

[0031] The electrolyte analyzer 100 according to this embodiment includes a signal processing circuit 157 that processes signals from the multiple electrodes during electrolyte concentration measurement, a differential amplifier circuit 156 that amplifies the signals from each electrode, and a signal input circuit 155 that receives signals from each electrode. The electromotive force of the ion-selective electrode is calculated by a calculation circuit (not shown) as a potential difference with the potential of the reference electrode 154 as the system ground. A control unit 200, which will be described later, has the functions of the signal processing circuit 157 and the calculation circuit, for example, and processes data during electrolyte concentration measurement.

[0032] 2 is a diagram showing an example of the configuration of the control unit of the electrolyte analyzer according to the first embodiment of the present invention. For example, the control unit 200 includes a CPU 201, a ROM 202, a RAM 203, a display 204, and a network I / F (interface) 205. Each of the components 201 to 205 is connected to a bus 206.

[0033] The CPU 201 controls the entire electrolyte analyzer. The ROM 202 stores various data such as a boot program that starts up the electrolyte analyzer and programs that control measurement processing and various components such as solenoid valves and pumps. The RAM 203 is used as a work area for the CPU 201.

[0034] Display 204 displays various data. In the present invention, display 204 not only allows the user to recognize the status of the device, but also functions as a human interface for operating and inputting program settings. Network I / F 205 controls data communication between the electrolyte analyzer and various external devices.

[0035] 2 performs processing related to electrolyte concentration measurement based on the detection value of the measurement unit 150. Furthermore, it can switch from processing related to electrolyte concentration measurement to processing related to cleaning at a predetermined time or other trigger.

[0036] A waste liquid section 160 was installed downstream of the measurement section 150 via a solenoid valve (for discharging waste liquid) 167. The liquid used for measuring the electrolyte concentration and for cleaning is discharged as waste liquid 161 by the control of the solenoid valve (for discharging waste liquid) 167 and a syringe pump 170.

[0037] (Calculation method of electrolyte concentration and order of potential measurement in the present invention) In an electrolyte analyzer, the electrolyte concentration is calculated using the difference between the base potential and the sample potential. Here, the base potential refers to the electromotive force of the reference solution. The sample potential refers to the electromotive force of the sample solution. If the analyzer is a dilution method analyzer, the electromotive forces of the reference solution and the sample solution diluted to a predetermined concentration are measured.

[0038] In the present invention, the order in which the base potential and sample potential are measured is particularly important. The details will be explained below in comparison with the prior art. In the following text, the term "carryover" refers to "the mixing of residual liquid from the previous sample into the solution to be measured at a level that affects the subsequent potential measurement."

[0039] Fig. 3 is a comparative diagram showing an outline of the measurement process according to the conventional technology and the embodiment of the present invention, in which Fig. 3(a) to (c) show the measurement process according to the conventional technology, and Fig. 3(d) shows the measurement process according to the embodiment of the present invention.

[0040] Figure 3 shows the measurement cycle for sample 1 and the subsequent sample 2. Time t flows from left to right in Figure 3, with the horizontal length of each rectangular frame representing the process time and the vertical length representing the liquid volume. Within the measurement cycle for sample 1, the measurement of the base potential is indicated by symbol B1, the measurement of the sample potential by symbol S1, and the cleaning process by symbol W1 (W1 can be used to indicate that W1 is performed multiple times). 1-1 , W 1-2 , W 1-3 The measurement period for sample 2 (shown by the dotted line frame in Figure 3) is symbol B2 for the measurement of the base potential, symbol S2 for the measurement of the sample potential, and symbol W2 for the cleaning process. The dotted arrow in Figure 3 indicates the carryover of sample 1.

[0041] As described in paragraph

[0006] of Patent Document 1, in conventional technology, the measurement cycle for one sample consists of measuring the base potential, measuring the sample potential, and performing a cleaning process in that order (hereinafter, performing processes in a predetermined order is referred to as a "sequence"). However, when the concentration of the electrolyte to be measured in a sample is very high and the difference in concentration between the sample and the next sample is large, using this sequence has been found to affect the analysis of the next sample. This is because residual liquid from the high-concentration sample remains on the inner surface of the flow path from the sample injection port (or the dilution section in the case of the dilution method) to the analysis section, and is not sufficiently washed away in the subsequent cleaning process and is carried over to the analysis cycle for the next sample (see Figure 3(a)). For example, when a high-concentration sample is followed by a low-concentration sample, the subsequent sample is affected by carryover from the previous sample.

[0042] To prevent this, it was necessary to increase the amount of cleaning solution (internal standard solution, dilution solution, diluted internal standard solution, etc.) used in the cleaning process (Fig. 3(b)) or to increase the number of cleanings (Fig. 3(c)). However, while Fig. 3(b) prevents carryover, it requires a large amount of cleaning solution. Also, Fig. 3(c) prevents carryover, but it requires a large amount of cleaning solution. As mentioned in the background art, such measures increase the running costs of the equipment.

[0043] In the present invention, it is important to form the measurement cycle for one sample by a sequence of sample potential measurement S, a cleaning step (the cleaning step is optional) W, and base potential measurement B. In this way, even if a high-concentration sample carries over, it only slightly affects the base potential used to calculate the electrolyte concentration of that sample, and is unlikely to affect the analysis cycle for the next sample (see Figure 3(d)). Note that, since high-concentration samples have very high concentrations of ions to be measured, even if their own carryover does have a slight effect on the measurement of the base potential used to calculate their own electrolyte concentration, the error is at an acceptable level and does not pose a substantial problem.

[0044] (Means for further improving processing speed made possible by changing the order in which potential measurements are performed) By adopting the sequence described in the previous section, the influence of high-concentration samples on the analysis cycle of the next sample is less likely to occur compared to conventional technology. Therefore, by appropriately combining the following methods, it is possible to further improve the overall processing speed.

[0045] FIG. 4 is a comparison diagram of the sequences of the electrolyte analyzer according to the conventional technology (Comparative Example 1) and Example 1 of the present invention. FIG. 4(a) shows the measurement process according to the conventional technology (Comparative Example 1), and FIG. 4(b) shows the measurement process according to Example 1 of the present invention. In Comparative Example 1 of FIG. 4(a), the cleaning process W1 is performed multiple times (W 1-1 , W 1-2 , W 1-3 ) is being carried out.

[0046] In contrast, according to Example 1 of the present invention shown in Figure 4(b), the overall processing time can be shortened compared to the processing time of Comparative Example 1, and the washing process can be reduced or omitted. Here, the reduction of the washing process refers to a reduction in the time spent on washing, a reduction in the amount of liquid used for washing, a reduction in the number of washings, etc. In the prior art (Comparative Example 1) of Figure 4(a), the number of washings per specimen was three (W 1-1 , W 1-2 , W 1-3 ), whereas in Example 1 shown in FIG. 4(b), the number of washes was two (W 1-1 , W 1-2 In Example 1 of FIG. 4, the number of washing times per two specimens is two (W 1-3 , W 2-3 ) was reduced.

[0047] FIG. 5 compares the sequences of an electrolyte analyzer according to the prior art (Comparative Example 2) and Example 2 of the present invention. FIG. 5(a) shows the measurement process according to the prior art (Comparative Example 2), and FIG. 5(b) shows the measurement process according to Example 2 of the present invention. Compared to the processing time of Comparative Example 1 in FIG. 5(a), Example 2 in FIG. 5(b) can omit the cleaning steps (W1 and W2) for Samples 1 and 2, thereby shortening the overall processing time. As shown in the example in FIG. 5(b), omitting the cleaning steps allows the measurement cycle to consist of a sequence consisting of only the measurement of the sample potential and the subsequent measurement of the base potential. Reducing or omitting the cleaning steps makes it possible to increase the number of samples that can be processed per unit time.

[0048] FIG. 6 is a comparison diagram of the sequences of an electrolyte analyzer according to the prior art (Comparative Example 3) and Example 3 of the present invention. FIG. 6(a) shows the measurement process according to the prior art (Comparative Example 3), and FIG. 6(b) shows the measurement process according to Example 3 of the present invention. In Comparative Example 3 of FIG. 6(a), the cleaning process W1 is performed multiple times (W 1-1 , W 1-2 , W 1-3 ) is being carried out.

[0049] If the mixing time is set long to adjust the timing of the entire sequence, even though it is sufficient, it is possible to reduce or omit the above-mentioned steps and shorten the mixing time to the necessary and sufficient time.By configuring the measurement cycle for one sample according to the present invention as a sequence of measuring the sample potential, a washing step (the washing step is optional), and measuring the base potential, the time for each step can be reduced, as shown in Figure 6(b), and it becomes possible to further increase the number of samples that can be processed per unit time.

[0050] (Additional technology that contributes to accuracy and precision) FIG. 7 is a comparison diagram of the sequences of the electrolyte analyzer according to the conventional technology (Comparative Example 4) and Example 4 of the present invention. FIG. 7(a) shows the measurement process according to the conventional technology (Comparative Example 4), FIG. 7(b) shows the measurement process according to Example 4-1 of the present invention, and FIG. 7(c) shows the measurement process according to Example 4-2 of the present invention. In Comparative Example 4 of FIG. 7(a), the cleaning process W1 is performed multiple times (W 1-1 , W 1-2 , W 1-3 ) is being carried out.

[0051] When measuring electrolyte concentrations using an ion-selective electrode, there are cases where changes in the temperature of the measurement environment (for example, when the temperature of a solution to be measured for potential changes as the solution passes through the ion-selective electrode) affect the measured value. In such cases, it is possible to reduce the aforementioned effects by adjusting the order in which potential measurements are performed.

[0052] For example, as shown in Example 4-2 of FIG. 7(c), the base potential measured before measuring the sample potential of the specimen to be measured is designated by the symbol B 1b and symbol B 2b The base potential measured after the sample potential measurement of the specimen to be measured is denoted by B 1a and symbol B 2a In addition, in Figure 7(b) and Figure 7(c), the aforementioned reduction in mixing time is also shown.

[0053] In Example 4-2 of FIG. 7(c), the base potential (referred to as "B" in the following formula 1) is measured before the sample potential of the specimen to be measured. b ") and the base potential (referred to as "B" in the following formula 1) measured after the sample potential measurement of the sample to be measured. a") are used at a certain ratio to calculate the potential difference. For example, it is possible to use the average value of both, or to use appropriate weighting for the calculation. In this way, even if there is a temperature change in the solution to be measured for potential measurement, the base potentials before and after the sample potential can be used, making it possible to reduce the influence of temperature changes. However, if the ratio of the base potential within the measurement period of the previous sample becomes excessively large, the result will be equivalent to the prior art, and the effects of the present invention will be impaired, which is undesirable. Even when weighting is used, it is appropriate that x in Equation 1 be greater than 0 and less than or equal to 0.5.

[0054] Base potential = B b ×x+B a ×(1-x) …(Formula 1)

[0055] The electrolyte analyzer 100 has connecting parts and junctions in the flow path. In particular, the connecting parts between the ion-selective electrodes in the measuring unit 150 have many irregularities. Liquid tends to remain on the irregularities on the inner surface of the flow path, which is one cause of carryover. By adopting the above-described sequence and increasing the liquid delivery speed, further contributions can be seen to not only the processing speed but also further improvements in accuracy and precision.

[0056] (Evaluation method when adjusting sequences) As mentioned above, when adjusting the process to further improve the processing speed, it is necessary to confirm that the high accuracy and precision of the measurement, which is a premise of the present invention, is maintained. The process needs to be adjusted appropriately depending on the purpose of the device, the user's operating method, the type of sample, individual differences (variations), etc. When adjusting, it is desirable to evaluate using the following method, for example. 1) For samples that the user may provide for measurement, the concentration distribution of the electrolyte to be measured is determined, and values ​​in the high concentration region and the low concentration region are determined from the distribution. 2) Create a pseudo sample containing a high concentration of the electrolyte to be measured (pseudo high-concentration sample). 3) Create a pseudo-sample containing a low concentration of the electrolyte to be measured (pseudo-low concentration sample). 4) Using the sequence to be evaluated, measure the electrolyte concentrations of pseudo-high-concentration samples and pseudo-low-concentration samples, alternately measuring both. 5) Using the measured values ​​of pseudo-low concentration samples, evaluate the discrepancy between the measured values ​​and theoretical values, the coefficient of variation of the measured values, etc., and confirm that the sequence is appropriately adjusted.

[0057] (Embodiment 1: Shortening of the cleaning process) In addition to the above-mentioned device configuration and method, the following was done.

[0058] The electrolyte analyzer used was manufactured by A&T Corporation. This analyzer is a type that dilutes the sample to be measured and analyzes it. It is also a type that uses an internal standard solution during measurement.

[0059] A small magnetic stirrer was used as the agitator in the dilution section 140. The agitator body (not shown in Figure 1) was located at the back of the wall of the dilution container 141, and a stirrer was placed on the inner surface of the dilution container. A flow path leading downstream was provided at the bottom of the dilution container 141.

[0060] A measurement unit was connected to the outlet of the flow path from the dilution container 141. A sodium ion selective electrode 153, a potassium ion selective electrode 152, and a chlorine ion selective electrode 151 were used in the measurement unit 150, along with a reference electrode 154 and a liquid earth electrode (omitted in FIG. 1) (all manufactured by A&T Corporation). These electrodes were connected in the following order from upstream: liquid earth electrode, chlorine ion selective electrode 151, potassium ion selective electrode 152, sodium ion selective electrode 153, and reference electrode 154, to form a flow path.

[0061] A phosphate buffer solution was used as the diluent, and an internal standard solution with a sodium concentration of 44 mmol / L, a potassium concentration of 1.2 mmol / L, and a chlorine concentration of 29 mmol / L was used.

[0062] The solution used in the cleaning process was a diluted internal standard solution. This was the same internal standard solution as described in the previous section, diluted with the same dilution solution as described in the previous section. This was done because using a solution diluted with the same dilution ratio as the diluted internal standard solution used to measure the base potential has the advantage of minimizing the potential difference between the cleaning process and when measuring the base potential.

[0063] A specified amount of diluent was introduced into the diluent container 141 from the diluent outlet 4 by a syringe pump 170 and a solenoid valve (for supplying diluent) 137, which were operated in response to instructions from the control unit 200. A sample (not shown) to be analyzed was aspirated from the sample container through the sample dispensing nozzle 112 by a syringe pump (not shown), which was operated in response to instructions from the control unit 200, and then a specified amount was dispensed into the diluent container 141. Thereafter, stirring was performed for a specified number of seconds using a small magnetic stirrer and a stirring bar 142 in the diluent container 141 to obtain a uniform diluted sample solution.

[0064] As in the previous section, a specified amount of dilution liquid was introduced into the dilution container 141. Furthermore, a specified amount of internal standard liquid was introduced into the dilution container 141 from the internal standard liquid outlet 3 by using the syringe pump 170 and the solenoid valve (for supplying internal standard liquid) 127, which were operated in response to instructions from the control unit 200. Thereafter, as in the previous section, stirring was performed for a specified number of seconds using the stirring bar 142 to obtain a uniform diluted internal standard liquid.

[0065] Human urine was used as a sample, and the sequence was as follows.

[0066] Comparative Example 1 The measurement cycle for the specimen to be measured was set to measurement of the base potential, measurement of the sample potential, and three washing steps (see FIG. 4(a)). [Example 1] The measurement cycle for the specimen to be measured was set to measurement of the sample potential, two cleaning steps, and measurement of the base potential (see FIG. 4(b)).

[0067] In Example 1, it was possible to shorten the process and improve the processing speed while maintaining the same accuracy and precision as in Comparative Example 1. In addition, it was possible to reduce the amounts of internal standard solution and diluent used, thereby reducing operating costs.

[0068] (Embodiment 2: Improvement of processing speed by omitting the cleaning process) The configuration of the device was the same as in embodiment 1. Example 2 is a sequence that assumes the analysis of samples with relatively small individual differences, such as human serum.

[0069] Human serum was used as a sample, and the sequence was as follows. Comparative Example 2 The measurement cycle for the specimen to be measured was set to measurement of the base potential, measurement of the sample potential, and one cleaning step (see FIG. 5(a)). [Example 2] The measurement period of the specimen to be measured was set to measurement of the sample potential and measurement of the base potential (see FIG. 5(b)).

[0070] In Example 2, it was possible to shorten the process and improve the processing speed while maintaining the same accuracy and precision as in Comparative Example 2. In addition, it was possible to reduce the amounts of internal standard solution and diluent used, thereby reducing operating costs.

[0071] (Embodiment 3: Improvement of processing speed by shortening mixing time) The configuration of the device was the same as in the first embodiment.

[0072] Urine was used as a sample, and the sequence was as follows: Comparative Example 3 The measurement cycle for the specimen to be measured was set to measurement of the base potential, measurement of the sample potential, and three washing steps (see FIG. 6(a)). [Example 3] The measurement cycle for the specimen to be measured was set to the following order: measurement of the sample potential, three cleaning steps, and measurement of the base potential, thereby shortening the stirring time when preparing the diluted sample solution and the diluted internal standard solution (see Figure 6(b)).

[0073] In Example 3, it became possible to shorten the process and improve the processing speed while maintaining the same accuracy and precision as in Comparative Example 3.

[0074] (Fourth embodiment: Handling large changes in environmental temperature) The configuration of the device is the same as in embodiment 1. Example 4 is a sequence assuming a case where the environmental temperature changes.

[0075] The sequence is as follows: Comparative Example 4: The measurement cycle for the specimen to be measured was set to three times: measurement of the base potential, measurement of the sample potential, and washing process (see FIG. 7(a)). The coefficient of the base potential (x in the above-mentioned formula 1) when calculating the electrolyte concentration was set to 1. [Example 4-1] The measurement cycle of the specimen to be measured was set to measurement of the sample potential, three washing steps, and measurement of the base potential (see Figure 7(b)). The coefficient of the base potential (x in the above-mentioned Equation 1) when calculating the electrolyte concentration was set to 0. [Example 4-2] The measurement cycle of the specimen to be measured was set to the order of measurement of the base potential, measurement of the sample potential, three cleaning steps, and measurement of the base potential. In addition, at this time, the "base potential measured before the sample potential measurement of the specimen to be measured" (symbol B in FIG. 7(c)) of specimen 2 was set to the order of "measurement of the base potential of the specimen to be measured" (symbol B in FIG. 7(c)). 2b ) is the "base potential measured after the sample potential measurement of the specimen to be measured" of specimen 1 (symbol B in Figure 7(c)). 1a ) was used in combination with the base potential (see Figure 7(c)). The coefficient of the base potential (x in Equation 1 above) used in calculating the electrolyte concentration was set to 0.5.

[0076] In Example 4-1, it was possible to shorten the process and improve the processing speed while maintaining the same accuracy and precision as in Comparative Example 1, compared to Comparative Example 4. In Example 4-2, in addition to the effect of Example 4-1, it also had the effect of suppressing the influence of changes in base potential resulting from the measurement environment on the calculated electrolyte concentration.

[0077] (Fifth embodiment: change of flow rate) The configuration of the device and the sequence were the same as in the first embodiment, and the liquid flow rates were as follows: [Comparative Example 5] Flow rate 1000μL / sec [Example 5] Flow rate: 1350 μL / sec

[0078] In Example 5, it was possible to reduce the incidence of the decrease in slope value during calibration that occurred in Comparative Example 5 (the incidence of the decrease in slope value was 3% in Comparative Example 5, but was 0% in Example 5). [Industrial Applicability]

[0079] As described above, the electrolyte analyzer according to the present invention is useful for measuring biological samples (for example, urine, serum, plasma, whole blood, cerebrospinal fluid, etc.), water quality, food, etc. [Explanation of symbols]

[0080] 3 Internal standard solution flow path 4 Diluent flow path 100 Electrolyte analyzer 110 Sample supply unit 111 cleaning solution 112 Sample dispensing nozzle 113 Mobile Crane 120 Internal standard solution supply section 121 Internal Standard Solution 127 Solenoid valve (for supplying internal standard solution) 130 Diluent supply unit 131 Diluted Solution 137 Solenoid valve (for supplying diluent) 140 Dilution section 141 Dilution container 142 Stirring bar 150 Measuring section 151 Chloride ion selective electrode 152 Potassium ion selective electrode 153 Sodium ion selective electrode 154 Reference Electrode 155 Signal input circuit 156 Differential Amplifier Circuit 157 Signal Processing Circuit 160 Waste liquid section 161 Wastewater 167 Solenoid valve (for waste liquid discharge) 170 Syringe Pump 200 control section 201 CPU (control unit) 202 ROM 203 RAM 204 Display 205 Network I / F 206 Bus

Claims

1. The measurement cycle of the electrolyte concentration of the sample is performed in the order of measurement of the electromotive force of the sample solution, an optional cleaning process, and measurement of the electromotive force of the reference solution, A method for analyzing electrolytes, comprising measuring the electrolyte concentration of the sample using the difference between the electromotive force of the sample solution and the electromotive force of the reference solution.

2. The measurement cycle of the electrolyte concentration of the sample is performed in the following order: measurement of the electromotive force of the reference solution, measurement of the electromotive force of the sample solution, a cleaning process which is an optional process, and measurement of the electromotive force of the reference solution; A method for calculating an electrolyte concentration of the sample using a difference between an electromotive force of the sample solution and an electromotive force of the reference solution after correction, the difference being calculated based on both an electromotive force of the reference solution measured before measuring the electromotive force of the sample solution and an electromotive force of the reference solution measured after measuring the electromotive force of the sample solution, The electromotive force of the reference solution after correction is calculated by "electromotive force of the reference solution measured before measuring the electromotive force of the sample solution × x + electromotive force of the reference solution measured after measuring the electromotive force of the sample solution × (1 - x)", and x in the above formula is greater than 0 and less than or equal to 0.

5.

3. a control unit that executes the measurement cycle of the electrolyte concentration of the sample in the following order: measurement of the electromotive force of the sample solution, a cleaning step which is an optional step, and measurement of the electromotive force of the reference solution; An electrolyte analyzer comprising a measurement unit that measures the electrolyte concentration of the sample using the difference between the electromotive force of the sample liquid and the electromotive force of the reference liquid.

4. a control unit that executes the measurement cycle of the electrolyte concentration of the sample in the following order: measurement of the electromotive force of the reference solution, measurement of the electromotive force of the sample solution, a cleaning step which is an optional step, and measurement of the electromotive force of the reference solution; a measuring unit that calculates an electrolyte concentration of the sample using a difference between the electromotive force of the sample liquid and the electromotive force of the reference liquid after correction, the difference being calculated based on both the electromotive force of the reference liquid measured before measuring the electromotive force of the sample liquid and the electromotive force of the reference liquid measured after measuring the electromotive force of the sample liquid; The measurement unit The electromotive force of the reference solution after correction is calculated by "electromotive force of the reference solution measured before measuring the electromotive force of the sample solution × x + electromotive force of the reference solution measured after measuring the electromotive force of the sample solution × (1-x)" and x in the above formula is greater than 0 and less than or equal to 0.

5.

5. a sample supply unit that supplies a sample to a dilution container; a diluent supply unit that supplies a diluent to the dilution container; a sample dilution unit that mixes the sample supplied to the dilution container with the diluent to generate a diluted sample solution; a measuring unit disposed downstream of the sample dilution unit and configured to measure the concentration of an electrolyte, which is a component to be measured, contained in the diluted sample solution; 5. The electrolyte analyzer according to claim 3, further comprising:

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