Electrolyte analyzer

Abstract

To provide an electrolyte analyzer that causes no drift of a measurement value and no deterioration in accuracy of measurement even for several tens of seconds of a waiting time from previous specimen measurement.SOLUTION: An electrolyte analyzer includes a sample providing unit 110, a diluent providing unit 130, a sample dilution unit 140, and a sample measurement unit 150. An internal volume of a diluent providing flow path 4 is 1700 μL or more and 5000 μL or less when an exit 1 of an electromagnetic valve 137 of the diluent providing unit 130 is taken as a start point and a bottom 2 of a nozzle 3 for discharge into a dilution container 141 is taken as an end point.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to an electrolyte analyzer that measures the electrolyte concentration of a diluted sample, and in particular to an electrolyte analyzer that measures the concentration of electrolytes (Na: sodium, K: potassium, Ca: calcium, etc.) in the analysis of biological samples, water quality, food, etc. [Background technology]

[0002] Since the late 1980s, development of devices that measure electrolyte concentrations using ion-selective electrodes has been underway. A variety of such devices have been developed and are currently in use. These devices are used not only for analyzing biological samples (e.g., urine, serum, plasma, whole blood, cerebrospinal fluid, etc.), but also for analyzing water quality and food.

[0003] The electrolyte analyzer uses an ion-selective electrode and a reference electrode to measure the electromotive force of a sample diluted with a diluent (hereinafter referred to as the "diluted sample solution") and also measures the electromotive force of a reference solution for comparison. Based on the measurement data for the diluted sample solution and the reference solution, the electrolyte concentration of the analyte contained in the diluted sample solution is measured. Specifically, 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. Furthermore, a standard solution is 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 force of the sample and the electromotive force of the standard solution (see, for example, Patent Document 1 below).

[0004] These electrolyte analyzers may output inaccurate analysis results due to fluctuations in measurement conditions, such as a sudden drop in electrode output or temperature changes in the measurement system. To prevent such problems, an electrolyte analysis method and electrolyte analyzer have been developed that can determine whether fluctuations in measurement conditions are within normal ranges or are abnormal (see, for example, Patent Document 2 below). This technology employs a method in which an internal standard solution is used, the dilution ratio of the diluted internal standard solution is calculated in advance, and this value is referenced each time to determine whether the fluctuations are within normal ranges or are abnormal. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Japanese Patent Application Publication No. 10-62375 [Patent Document 2] Japanese Patent Application Laid-Open No. 2010-133742 Summary of the Invention [Problem to be solved by the invention]

[0006] In electrolyte analyzers, the measurement value of a subsequent sample may be affected by the length of the "waiting time between the completion of measurement of the previous sample and the measurement of the next sample" (hereinafter abbreviated as "waiting time" in this document). For example, if measurement is resumed several tens of seconds after the completion of measurement of the previous sample, the measurement value of the subsequent sample may drift (a tendency for the measurement value to gradually increase or decrease). This phenomenon leads to a decrease in the accuracy and precision of the analysis, so it is desirable to eliminate it as much as possible.

[0007] The causes and mechanisms of the aforementioned phenomenon are still not fully understood. Although temperature changes, the presence or absence of elution from wetted parts, and the generation of static electricity are suspected, a precise explanation is still not available. However, there are several methods to essentially eliminate the aforementioned phenomenon. For example, (1) continuing to measure dummy samples even when there are no samples to be measured, (2) performing multiple cleanings (not only the "acclimation cleaning" described below, but also excessive cleaning processes beyond that) before resuming measurements after a waiting period, and (3) periodically flowing liquids such as diluents and internal standards into the flow path during waiting periods have been attempted.

[0008] However, adopting such a method has various disadvantages, such as the time required to process one sample being long and the high cost due to the use of unnecessary consumables. In today's world, analyzers are required to provide measurement results quickly without making users wait, and to be economical and environmentally friendly. Therefore, there has been a demand for an electrolyte analyzer that does not affect measurement results after restarting even in the case of long waiting times, does not require excessively long processing times for one sample, has a simple structure, and can be operated at low cost.

[0009] In view of the above problems, an object of the present invention is to provide an electrolyte analyzer that does not cause drift in measured values ​​even when the standby time is long, and that is capable of performing highly accurate and precise analysis. [Means for solving the problem]

[0010] In order to solve the above problems, the electrolyte analyzer of the present invention is an electrolyte analyzer having 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 sample measurement unit that measures the concentration of an electrolyte, which is a measured component contained in the diluted sample solution, while extracting the diluted sample solution from the dilution container, and is characterized in that the internal volume of the dilution liquid supply flow path (in the present invention, this may be abbreviated as the "dilution liquid flow path"), which starts at the solenoid valve outlet of the dilution liquid supply unit and ends at the base of the nozzle for discharging into the dilution container, is 1700 μL or more and 5000 μL or less.

[0011] According to the above configuration, even if the waiting time is long, no drift in the measured value occurs, and highly accurate and precise analysis is possible.

[0012] The above-mentioned electrolyte analyzer is also characterized in that a space for storing diluent (referred to as a "diluent chamber" in the present invention; even when a diluent chamber is installed, the "diluent supply flow path" includes the diluent chamber) is provided midway through the diluent supply flow path.

[0013] This configuration not only prevents drift in measured values ​​even when the standby time is long, but also makes it easier to remove air bubbles that may occur in the diluent supply flow path upstream of the diluent chamber, enabling more accurate and precise analysis. [Effects of the Invention]

[0014] The present invention has the advantage that no drift in measured values ​​occurs even when the standby time is long, enabling highly accurate and precise analysis. Furthermore, when a diluent chamber is installed, it also has the advantage that if bubbles are generated in the diluent supply flow path upstream of the diluent chamber, the bubbles can be easily removed, enabling even more accurate and precise analysis. [Brief explanation of the drawings]

[0015] [Figure 1] FIG. 1 is a schematic diagram of an electrolyte analyzer according to an embodiment of the present invention. [Figure 2] FIG. 2 is a schematic diagram of an electrolyte analyzer according to another embodiment of the present invention. [Figure 3] FIG. 3 is a schematic perspective view of a diluent chamber according to another embodiment of the present invention. [Figure 4] FIG. 4 is a configuration diagram of the control unit of the electrolyte analyzer according to the embodiment of the present invention. [Figure 5] FIG. 5 is a flow chart showing the measurement procedure (measurement protocol) used in the comparative examples and examples. DETAILED DESCRIPTION OF THE INVENTION

[0016] The following describes in detail an embodiment of the present invention, but the present invention is not limited to this.

[0017] (Configuration of the electrolyte analyzer of the present invention) Fig. 1 is a schematic diagram of an electrolyte analyzer according to an embodiment of the present invention. The electrolyte analyzer according to the embodiment of the present invention comprises a sample supply unit 110, an internal standard solution supply unit 120, a diluent supply unit 130, a sample dilution unit 140, a sample measurement unit 150, a waste liquid unit 160, and a control unit 400 (not shown in Fig. 1, the configuration of which is shown in Fig. 4).

[0018] 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 113, and a cleaning solution 111.

[0019] 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 by the movement of movable crane 113 to sample dilution section 140, where it is 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.

[0020] The internal standard solution supply unit 120 is composed of a container for a standard solution (internal standard solution) 121 and an electromagnetic valve (for supplying the internal standard solution) 127. The solution is delivered by a syringe pump.

[0021] The diluent supply unit 130 is composed of a container for diluent 131 and an electromagnetic valve (for diluent supply) 137. The liquid is delivered by a syringe pump. 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.

[0022] In the present invention, the internal volume of the flow path from the outlet 1 of the solenoid valve (for supplying diluent) 137 to the base 2 of the nozzle 3 for discharging the diluent into the diluent container 141 (the flow path for supplying diluent ranging from symbol 1 to symbol 2 is defined as the diluent flow path 4) is important.

[0023] In analytical instruments that use piping to form flow paths and allow liquids to flow through them, it is common to design the internal volume of the flow path to be as small as possible. The diameter of the piping is often made as small as possible, and the length of the piping is often kept as short as possible. This is because if the internal volume of the flow path is large, there will be adverse effects such as large pressure changes when the liquid is being sent, and an increase in the amount of liquid other than that used for actual measurement (liquid required only for system operation), which can lead to inefficiencies.

[0024] However, the inventors discovered that, although the details of the principle are unknown, increasing the internal volume of the diluent flow path 4 to a certain extent makes it extremely unlikely that drift in the measurement value will occur, even if the standby time is long. Therefore, the solution was to increase the internal volume of the diluent flow path 4 from 1700 μL to 5000 μL (this internal volume is approximately 2 to 25 times larger than the same portion of a conventional product). Increasing the internal volume can be achieved by using appropriate methods, such as increasing the diameter, lengthening the piping, or installing a liquid reservoir (referred to as a "diluent chamber" in the present invention) midway through the flow path.

[0025] Fig. 2 is a schematic diagram of an electrolyte analyzer according to another embodiment of the present invention. Fig. 3 is a schematic perspective view of a diluent chamber according to another embodiment of the present invention. The electrolyte analyzer according to the embodiment of the invention shown in Fig. 2 is a configuration example that incorporates the diluent chamber 5 shown in Fig. 3 in addition to the same components as those in Fig. 1. Fig. 2 is a schematic perspective view of a diluent chamber according to another embodiment of the present invention. The diluent chamber 5 is provided in a part of the diluent flow path 4, and removes air bubbles from the diluent flowing through the diluent flow path 4.

[0026] The material for the diluent flow path 4 shown in Figure 1 and the diluent chamber 5 shown in Figure 2 need only be durable enough to withstand the components of the diluent, and can be freely selected from Teflon (registered trademark), silicone, glass, ceramic, stainless steel, corrosion-coated metal, etc. Considering ease of handling, it is appropriate to select a flexible resin for the piping portion of the diluent flow path 4, and a resin that allows the interior to be seen (e.g., polyvinyl chloride, acrylic resin, polycarbonate, polyethylene terephthalate, polybutylene terephthalate, polystyrene, AS resin, ABS resin, etc.) or glass for the diluent chamber 5.

[0027] The sample 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 suits the purpose, such as a stirring blade or a magnetic stirrer. Considering the efficiency of rinsing the sample and ease of maintenance, it is desirable to use a small magnetic stirrer (Figure 1 shows an example in which a magnetic stirrer is used. Reference numeral 142 denotes a stirring bar placed in the dilution container 141).

[0028] The material of the dilution container 141 can be appropriately selected from metal, glass, resin, etc. Among them, from the viewpoint of visibility and workability, it is desirable to use a transparent resin (for example, polyvinyl chloride, acrylic resin, polycarbonate, polyethylene terephthalate, polybutylene terephthalate, polystyrene, AS resin, ABS resin, etc.). In addition, if a magnetic stirrer is used as the stirrer, it is optimal to use a resin with high slidability (for example, fluororesin, polyacetal, etc.) in the range in which the stirrer 142 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 discharge nozzle 3. 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 sample measurement unit 150 installed downstream.

[0030] The sample measurement unit 150 is composed of various ion-selective electrodes and a reference electrode 154. Examples of ion-selective electrodes include a chloride ion-selective electrode 151, a potassium ion-selective electrode 152, a sodium ion-selective electrode 153, and a magnesium ion-selective electrode (not shown). 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 that of the electrolyte concentration analysis.

[0031] A waste liquid section 160 is installed downstream of the sample 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 under the control of the solenoid valve (for discharging waste liquid) 167 and a syringe pump 170.

[0032] The electrolyte analyzer according to this embodiment includes a signal input circuit 181 that inputs signals to these multiple electrodes during electrolyte concentration measurement processing, a differential amplifier circuit 182 that amplifies the signals from each electrode, and a signal processing circuit 183 that processes the signals from each electrode. The electromotive force of the ion selective electrode is calculated by an arithmetic circuit (not shown) as a potential difference with the potential of the reference electrode 154 as the system ground. A control unit 400, which will be described later, has the functions of, for example, the signal processing circuit 183 and the arithmetic circuit, and processes data during electrolyte concentration measurement processing.

[0033] 4 is a diagram showing an example of the configuration of a control unit of an electrolyte analyzer according to an embodiment of the present invention. For example, control unit 400 includes CPU 401, ROM 402, RAM 403, display 404, and network I / F (interface) 405. Each of components 401 to 405 is connected to bus 406.

[0034] The CPU 401 controls the entire electrolyte analyzer. The ROM 402 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 403 is used as a work area for the CPU 401.

[0035] Display 404 displays various data. In the present invention, display 404 not only allows the user to recognize the status of the device, but also functions as a human interface for inputting program settings. Network I / F 405 controls data communication between the electrolyte analyzer and various external devices.

[0036] 4 performs processing related to electrolyte concentration measurement based on the detection value of the sample measurement unit 150. Furthermore, the control unit 400 can perform control to switch from processing related to electrolyte concentration measurement to processing related to cleaning at a predetermined time or other trigger.

[0037] (Comparative Examples 1 to 3) An electrolyte analyzer was fabricated in which the configuration other than the internal volume of the diluent flow path 4 was the same as that described above (including FIG. 1).

[0038] The sample measurement section 150 employed a sodium ion selective electrode 153, a potassium ion selective electrode 152, and a chlorine ion selective electrode 151, together 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.

[0039] The internal volume of the diluent flow path 4 in each comparative example is shown below. [Comparative Example 1] Internal volume: 196 μL (piping diameter: 1 mm, piping length: 250 mm) [Comparative Example 2] Internal volume: 358 μL (piping diameter: 1.35 mm, piping length: 250 mm) [Comparative Example 3] Internal volume: 785 μL (piping diameter: 2 mm, piping length: 250 mm)

[0040] The variability of measurement values ​​from an electrolyte analyzer is typically expressed as the coefficient of variation (hereafter abbreviated as "CV") when the same sample is measured repeatedly. Therefore, to enable evaluation using CV, 10 measurements were defined as one set (hereafter, this may be referred to as "n = 10 measurements"), and 25 sets of repeated measurements were performed, with waiting times and conditioning washes between sets. Since each set contains measurements from 1 to 10, the tenth measurement in each set serves as the pre-sample for the next set. Note that conditioning washes refer to the flow path from the sample dilution unit 140 to the sample measurement unit 150 prior to sample measurement, in which a small amount of diluted internal standard solution is passed through the flow path to condition the liquid-contacting parts and the sensitive membrane of the ion-selective electrode.

[0041] FIG. 5 is a flowchart showing the measurement procedure (measurement protocol) used in the comparative example and the example. The control unit 400 (CPU 401) automatically executes, for example, the example measurement procedure shown in FIG. 5. Note that control by the control unit 400 is not essential, and each part of the device may be manually operated in the following procedure. First, the control unit 400 starts the 0th set of measurement as a preparation stage (step S500a). Next, the waiting time is set to 44 seconds (step S500b), and after performing a conditioning wash (step S500c), the first set of measurement is started using horse serum as a sample (step S501a).

[0042] Furthermore, after the first set of measurements, the control unit 400 starts the second set of measurements (step S502a) after a 44-second waiting time (step S501b) and a conditioning wash (step S501c). Thereafter, the control unit 400 repeats the process from the third set of measurements (step S503a) to the 25th set of measurements (step S525a) in the same set-by-set cycle as above.

[0043] After the measurements, the control unit 400 uses the 10 measurement values ​​of each set to calculate the CV according to the following (Equation 1).

[0044] Coefficient of variation (CV) = standard deviation / average value (Equation 1)

[0045] Here, the following two points are used to evaluate the dispersion of the measured values. Note that the "CV = 0.3% or less" used in 2) is a generally acceptable condition when discussing the quality of the operation of an electrolyte analyzer. 1) The lowest and highest CV values ​​in 25 sets of measurements 2) Number of times CV was 0.3% or less in 25 sets of measurements

[0046] The results are set forth in Table 1 below.

[0047] (Examples 1 to 3) An apparatus having the same configuration as Comparative Examples 1 to 3 was fabricated, except that the internal volume of the diluent flow path 4 was set to 1700 to 5000 μL, and similar measurements and evaluations were carried out. In Example 3, a diluent chamber 5 (FIG. 3) was placed midway along the diluent flow path 4, as shown in FIG. 2. In Example 3, the removal of air bubbles brought in from upstream of the diluent flow path 4 was also visually confirmed. [Example 1] Internal volume: 1767 μL (piping diameter: 3 mm, piping length: 250 mm) [Example 2] Internal volume: 3095 μL (piping diameter: 3.97 mm, piping length: 250 mm) [Example 3] Internal volume: 3614 μL (piping diameter: 1.35 mm, piping length: 310 mm)

[0048] The results of Examples 1 to 3 are shown in Table 1 together with Comparative Examples 1 to 3.

[0049] [Table 1]

[0050] (evaluation) As shown in Table 1, when the internal volume of the diluent flow path 4 was set to 1700 to 5000 μL (Examples 1 to 3), the minimum and maximum CV values ​​in 25 sets of measurements were kept lower than those in the comparative example for both the potassium ion selective electrode 152 and the sodium ion selective electrode 153. Furthermore, in the examples, the CV was kept to 0.3% or less in all of the 25 sets of measurements.

[0051] This indicates that, when the internal volume of the diluent flow path 4 is set to 1700 to 5000 μL as in the embodiment, an electrolyte analyzer can be provided in which the analysis after restart is less affected even when the standby time is as long as several tens of seconds. Furthermore, when the diluent chamber 5 is disposed midway through the diluent flow path 4, not only the above-mentioned effect but also the bubble removal effect was observed as a secondary effect. [Industrial Applicability]

[0052] As described above, the electrolyte analyzer according to the present invention is useful for measuring electrolyte concentrations in biological samples (for example, urine, serum, plasma, whole blood, cerebrospinal fluid, etc.), water, food, etc. with high accuracy and precision. [Explanation of symbols]

[0053] 1. Dilution liquid supply solenoid valve outlet 2 The base of the nozzle for discharging the diluted solution into the dilution container 3. Nozzle for discharging the diluted solution into the dilution container 4 Diluent flow path 5 Diluent Chamber 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 Sample dilution section 141 Dilution container 142 Stirring bar 150 Sample Measurement Section 151 Chloride ion selective electrode 152 Potassium ion selective electrode 153 Sodium ion selective electrode 154 Reference Electrode 160 Waste liquid section 161 Wastewater 167 Solenoid valve (for waste liquid discharge) 170 Syringe Pump 181 Signal input circuit 182 Differential Amplification Circuit 183 Signal Processing Circuit 400 control section 401 CPU (control unit) 402 ROM 403 RAM 404 Display 405 Network I / F 406 Bus

Claims

1. 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 sample measurement unit that measures the concentration of an electrolyte, which is a component to be measured, contained in the diluted sample solution while extracting the diluted sample solution from the dilution container, An electrolyte analyzer characterized in that the internal volume of the diluent supply flow path, which starts from the solenoid valve outlet of the diluent supply unit and ends at the base of the nozzle for discharging into the diluent container, is 1700 μL or more and 5000 μL or less.

2. 2. The electrolyte analyzer according to claim 1, wherein a diluent chamber is disposed on the diluent supply flow path.

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