Automatic analysis device and electrolyte measurement method for automatic analysis device

Abstract

In order to provide an automatic analysis device that prevents the ion concentration of an internal standard liquid or a specimen from being detected as higher than an actual value while allowing simplified reagent replenishment, the following configuration is achieved.　This automatic analysis device comprises a measurement unit that measures the electrolyte concentration of a test specimen. The automatic analysis device further comprises a control unit that executes, when multiple consecutive measurements are to be performed on an internal standard sample having a known electrolyte concentration in the measurement unit, control to perform, prior to the measurements on the internal standard sample, a measurement preparation operation that is similar to the measurement on the test specimen and includes at least a washing step for washing the measurement unit, and then perform the measurements on the internal standard sample.

Description

Automatic analyzer and electrolyte measurement method for automatic analyzer

[0001] The present invention relates to an automatic analyzer and an electrolyte measurement method for the automatic analyzer.

[0002] An ion selective electrode (ISE) can quantify the ions to be measured in a sample by contacting the detection element with the sample liquid and measuring the potential difference with the reference electrode. Due to this simplicity, it is widely used in the analytical field. In particular, a flow-type ion selective electrode has a detection element installed in the flow path through which the sample liquid flows, allowing continuous quantification of the ion concentrations of multiple samples.

[0003] Therefore, flow-type electrolyte concentration measuring devices equipped with flow-type ion-selective electrodes are installed in automatic biochemical analyzers and the like, and are characterized by their ability to analyze electrolyte concentrations in samples such as serum and urine with high precision and high throughput.

[0004] Flow-type electrolyte concentration measuring devices typically analyze multiple ions (sodium ions, potassium ions, calcium ions, chloride ions, etc.) simultaneously, and are therefore equipped with multiple ion-selective electrodes corresponding to the ions to be detected. These electrodes are generally consumables, and their useful life is typically reached after a few months or several thousand tests, and they are replaced with new electrodes.

[0005] In addition, to ensure the accuracy of analytical values, several types of reagents are routinely used within the electrolyte concentration measuring device to check the device's condition. For example, if the concentration of the internal standard solution differs significantly from the design value, the device is considered to be in an irregular state, and even if general samples are analyzed in that state, analytical accuracy may not be guaranteed. This periodic measurement of the internal standard solution is called an ISE check (instrument health check).

[0006] A method for ISE check (instrument health check) by periodic measurement of an internal standard solution is described in, for example, Patent Document 1.

[0007] Japanese Patent Application Laid-Open No. 2018-17543

[0008] The present inventors have examined the technology described in Patent Document 1 and found that the technology described in Patent Document 1 may detect an ion concentration of an internal standard solution that is higher than the actual value. If the ion concentration of an internal standard solution is detected to be higher than the actual value, there is a possibility that the device may be judged to be abnormal when there is no abnormality, or that the device may be judged to be normal when there is an abnormality. The present inventors have conducted extensive research into the cause of such cases where the ion concentration of an internal standard solution is detected to be higher than the actual value, and have arrived at the present invention.

[0009] An object of the present invention is to provide an automatic analyzer and an electrolyte measurement method for an automatic analyzer that can diagnose the state of the device in a state closer to actual measurement and correctly determine the presence or absence of an abnormality with higher accuracy during an ISE check (device health check) based on periodic measurement of an internal standard solution.

[0010] The present invention has the following configuration for solving the above-mentioned problems.

[0011] An automatic analyzer having a measurement unit that measures the electrolyte concentration of a specimen sample, wherein when the measurement unit measures an internal standard sample whose electrolyte concentration is known in advance multiple times in succession, the automatic analyzer is equipped with a control unit that controls the measurement unit to perform a measurement preparation operation similar to that for measuring the specimen sample, including at least a cleaning step for the measurement unit, before measuring the internal standard sample, and then measure the internal standard sample; and an electrolyte measurement method for the automatic analyzer.

[0012] According to the present invention, it is possible to provide an automatic analyzer and an electrolyte measurement method for an automatic analyzer that simplify reagent replenishment while preventing the ion concentration of an internal standard solution or a sample from being detected as higher than the actual value.

[0013] Problems, configurations, and effects other than those described above will become apparent from the following description of the embodiments.

[0014] Block diagram showing the overall configuration of the flow-type electrolyte concentration measuring device targeted by the present invention. Flowchart at the time of starting up the electrolyte concentration measuring device targeted by the present invention. Flowchart during continuous analysis of electrolyte concentration measurement targeted by the present invention. Flowchart at the time of switching the reagent bottle for electrolyte concentration measurement targeted by the present invention. Flowchart for explaining the details of S203 in the flowchart at the time of starting up the device described in FIG. 2A. Flowchart for explaining the details of S203 in the flowchart at the time of starting up the device described in FIG. 2A. Flowchart for explaining the details of S231 to S234 in the flowchart at the time of switching the reagent bottle described in FIG. 2C (Prior art). Flowchart for explaining the details of S231 to S234 in the flowchart at the time of switching the reagent bottle described in FIG. 2C (The present invention). Diagram showing the QC results when applying the flow (Prior art) shown in FIG. 4A. Diagram showing the QC results when applying the flow (The present invention) shown in FIG. 4B. Diagram showing another device configuration applicable to the present invention. Diagram showing another device configuration applicable to the present invention. Diagram representing the concept of the ISE check method according to the present invention. Diagram representing the concept of the calibration curve correction method according to the present invention. Diagram showing an example of the result display screen of the ISE check according to the present invention. Diagram showing another device configuration applicable to the present invention

[0015] First, an electrolyte concentration measuring device (also referred to as a flow-type electrolyte concentration measuring device), which is the object of the present invention, will be described. FIG. 1 is a schematic diagram showing an example of a flow-type electrolyte concentration measuring device 100 according to the present embodiment.

[0016] This flow-type electrolyte concentration measuring device 100 includes a measurement unit 170, a concentration calculation unit 173, a display unit 174, a control unit 175, and an input unit 176.

[0017] The measurement unit 170 includes an ion-selective electrode 110 composed of three types of electrodes: a chloride ion electrode, a potassium ion electrode, and a sodium ion electrode, and a reference electrode 104. Using a sipper syringe pump 133, a reference electrode solution is introduced from a reference electrode solution bottle 161 into the flow path of the reference electrode 104.

[0018] Meanwhile, an internal standard solution dispensed from an internal standard solution bottle 141 into a dilution tank 120, a diluted sample, and the like are introduced into the flow path of the ion selective electrode 110. The potential difference (electromotive force) between the reference electrode 104 and each ion selective electrode 110 varies depending on the concentration of the analyte ion in the solution introduced into the flow path of each ion selective electrode, so the electromotive force is measured by a potential measuring unit 171 and the ion concentration is calculated by a concentration calculating unit 173. The calculation method will be described in detail later.

[0019] In the flow-type electrolyte concentration measuring device 100, a reference electrode solution, an internal standard solution, and a dilution solution are constantly used, so if any of the reagents runs short during continuous analysis, the analysis will become impossible.

[0020] This flow-type electrolyte concentration measuring device 100 has a reagent amount monitoring mechanism (e.g., a weight sensor that measures the weight of the reagent bottle) that monitors the amount of reagent in each of the reagent bottles 141, 151, and 161, and has the function of comparing the weight of the reagent bottle with a preset value, and if the weight of the reagent bottle becomes lighter than the preset weight, displaying this fact on the display unit 174 and prompting the device operator to switch to a bottle that contains sufficient reagent.

[0021] The reagent amount monitoring mechanism is not limited to the method using a weight sensor, and a level gauge that monitors the liquid level of the reagent liquid inside the reagent bottle may also be used. Furthermore, even if a reagent amount monitoring mechanism is not provided, the amount of reagent consumed may be managed by the control unit 175 based on the number of analyses and the syringe operation history. Furthermore, although Fig. 1 shows a configuration in which the diluent is supplied from a reagent bottle, it may also be supplied from the piping for water used in the analyzer (referred to as system water) instead of from a reagent bottle.

[0022] Although not explained here, the solenoid valve (ribbon-shaped with opposing triangles) in the figure can switch or open / close the flow path, operating appropriately according to the direction and timing of introducing the liquid. It is also possible to install two bottles of the same type of reagent (e.g., internal standard solution) and add a mechanism that automatically switches to the other bottle when the reagent in one bottle runs low. Adding this mechanism allows the instrument operator to replace the empty bottle with a new bottle filled with reagent at any time while the instrument is using the other bottle. In this case, more than two bottles may be used, and multiple bottles may be provided for only some reagents that are used in large quantities, rather than for all types of reagents used in the instrument.

[0023] Next, the electrolyte concentration measurement flow in the flow-type electrolyte concentration measurement device 100 will be described using FIGS. 2A to 2C. First, the setup procedure for the device will be described using FIG. 2A. First, the device is powered on (not shown) to start up (S201), and the internal standard solution bottle 141, dilution solution bottle 151, and reference electrode solution bottle 161 are installed (S202). After temperature adjustment, two types of standard solutions with known concentrations (the lower-concentration standard solution is labeled L and the higher-concentration standard solution is labeled H in FIG. 2) are measured to obtain calibration curves for the chloride ion electrode, potassium ion electrode, and sodium ion electrode of the ion-selective electrode 110, and a slope (a formula for converting measured potential values ​​into concentrations; this is usually called a slope because it is a diagonal line; details will be described later) is calculated (S203). Next, the concentration of the internal standard solution (usually with a known concentration between L and H) is calculated based on the potential measured by the ion-selective electrode (S204).

[0024] The apparatus may further include a concentration calculation unit that determines a formula for calculating the concentration of the specimen sample based on the measurement results of at least two standard samples with different concentrations whose electrolyte concentrations are known in advance, and the concentration calculation unit may correct the formula based on the measurement results of the electrolyte concentrations of the internal standard sample, and calculate the concentration of the specimen sample using the corrected formula.

[0025] Here, the specific operations of S203 and S204 will be explained using the flow diagram of FIG. 3 (although the operations are spread across two diagrams, FIG. 3A and FIG. 3B, the flow itself is continuous. Here, FIG. 3A and FIG. 3B will be collectively explained as FIG. 3).

[0026] First, a known low-concentration standard solution (L in FIG. 2 ) contained in a reagent bottle (not shown) is dispensed into the dilution tank 120 using a reagent dispensing nozzle (not shown). Then, the dilution syringe pump 132 is operated to dispense the dilution solution in the dilution bottle 151 into the dilution tank 120, diluting the known low-concentration standard solution (L) at a preset ratio D (S301). Meanwhile, reference electrode solution is introduced from the reference electrode solution bottle 161 into the flow path of the reference electrode 104 (S302). Next, the diluted known low-concentration standard solution (L) in the dilution tank is sucked through the sipper nozzle 107 and introduced into the flow path of the ion-selective electrode 110 (S303).

[0027] The reference electrode solution supplied to the flow path of the reference electrode 104 and the diluted known low-concentration standard solution (L) supplied to the flow path of the ion selective electrode 110 come into contact at the liquid junction (the flow path on the ion electrode side of the reference electrode 104). In this state, the potential difference (electromotive force) between each ion selective electrode and the reference electrode 104 is measured by the potential measuring unit 171 (S304).

[0028] Next, the vacuum pump 112 is driven, and the remaining liquid in the dilution tank 120 is sucked up by the vacuum suction nozzle 106 and discarded into the waste liquid tank 111 (S305). Thereafter, the internal standard solution syringe pump 131 is operated to dispense the internal standard solution from the internal standard solution bottle 141 into the dilution tank 120 from the internal standard solution supply nozzle 109 (S306). Meanwhile, the sipper syringe pump 133 is operated to introduce the reference electrode solution from the reference electrode solution bottle 161 into the flow path of the reference electrode 104 (S307).

[0029] Next, the internal standard solution is sucked from the dilution tank 120 through the sipper nozzle 107, and the flow path of the ion selective electrode 110 is filled with the internal standard solution (S308). Then, the potential difference (electromotive force) between each electrode of the ion selective electrode 110 and the reference electrode 104 is measured by the potential measuring unit 171 (S309).

[0030] Thereafter, the vacuum pump 112 is driven again, and the remaining liquid in the dilution tank 120 is sucked up by the vacuum suction nozzle 106 and disposed of in the waste tank 111 (S310). Thereafter, a known high-concentration standard solution (H) contained in a reagent bottle (not shown) is dispensed into the dilution tank 120 by the reagent dispensing nozzle (not shown), and then the diluent syringe pump 132 is operated to dispense the diluent in the diluent bottle 151 through the diluent supply nozzle 108 into the dilution tank 120, thereby diluting the known high-concentration standard solution (H) at the set ratio D (S311). Meanwhile, the sipper syringe pump 133 is operated to introduce the reference electrode solution from the reference electrode solution bottle 161 into the flow path of the reference electrode 104 (S312).

[0031] Next, the diluted known high-concentration standard solution (H) in the dilution tank 120 is sucked through the sipper nozzle 107 and introduced into the flow path of the ion selective electrode 110 (S313). The reference electrode solution supplied to the flow path of the reference electrode 104 and the diluted known high-concentration standard solution (H) supplied to the flow path of each electrode of the ion selective electrode 110 come into contact at the liquid junction. In this state, the potential difference (electromotive force) between each electrode of the ion selective electrode 110 and the reference electrode 104 is measured by the potential measuring unit 171 (S314).

[0032] Next, the vacuum pump 112 is driven, and the remaining liquid in the dilution tank 120 is sucked up by the vacuum suction nozzle 106 and discarded into the waste liquid tank 111 (S315). Thereafter, the internal standard solution syringe pump 131 is operated, and the internal standard solution in the internal standard solution bottle 141 is dispensed from the internal standard solution supply nozzle 109 to the dilution tank 120 (S316). Meanwhile, the sipper syringe pump 133 is operated, and the reference electrode solution is introduced from the reference electrode solution bottle 161 into the flow path of the reference electrode 104 (S317).

[0033] Next, the internal standard solution in the dilution tank 120 is sucked from the sipper nozzle 107, filling the flow path of the ion selective electrode 110 with the internal standard solution (S318). In this state, the potential difference (electromotive force) between each electrode of the ion selective electrode 110 and the reference electrode 104 is measured by the potential measuring unit 171 (S319).

[0034] Thereafter, the vacuum pump 112 is driven again, and the remaining liquid in the dilution tank 120 is sucked up by the vacuum suction nozzle 106 and disposed of in the waste liquid tank 111 (S320).

[0035] From the electromotive force measured by the potential measuring unit 171 through the above operations, the concentration calculating unit 173 calculates the slope sensitivity SL corresponding to the calibration curve using the following formula (S321).

[0036] (A) Slope sensitivity SL = (EMFH - EMFL) / (LogCH - LogCL) ... (Equation 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 The above operation is called the calibration operation. Note that the slope sensitivity SL corresponds to 2.303 x (RT / zF) in the Nernst equation, E = E0 + 2.303 x (RT / zF) x log(f x C) (E0: constant potential determined by the measurement system, z: valence of the ion to be measured, F: Faraday constant, R: gas constant, T: absolute temperature, f: activity coefficient, C: ion concentration). Although it can be calculated from the temperature and the valence of the ions to be measured, in order to further improve the analytical accuracy, the slope sensitivity SL specific to the electrode is determined by the above-mentioned calibration in this device.

[0037] Although the specific measurement sequence for S203 has been described above in detail, a different procedure may be used as long as two types of liquids with different ion concentrations are introduced into the flow path and the electromotive force can be measured.

[0038] Next, the concentration of the internal standard solution is calculated from the slope sensitivity obtained in S203 and the measured potential (electromotive force) of the internal standard solution (S204).

[0039] (B) Internal Standard Solution Concentration CIS = CL x 10a (Equation 2) a = (EMFIS - EMFL) / SL (Equation 3) CIS: Internal Standard Solution Concentration EMFIS: Electromotive Force of Internal Standard Solution Next, the control unit 175 determines whether the ion concentration of the internal standard solution is within a preset normal concentration range (S205). If it is within the normal range, the system proceeds to the general sample analysis flow shown in Figure 2B. If it is outside the normal range, an alarm is issued (S206). If the internal standard solution concentration is significantly different from the design value, the system is considered to be in an irregular state, and analytical accuracy may not be guaranteed even if a general sample is analyzed under such conditions. This periodic measurement of the internal standard solution is called an ISE check (instrument health check).

[0040] An example of the ISE check results displayed on the display unit 174 in FIG. 1 is shown in FIG. 10. The measurement results of the internal standard solutions of sodium, potassium, and chlorine are displayed as concentrations. The lower and upper limit concentrations of sodium, potassium, and chlorine are also displayed on the same screen. If the measured internal standard solution concentration deviates from the range between the lower and upper limits as a result of the ISE check, the device determines that the device is in an irregular state and displays an alarm on the screen (not shown).

[0041] The details of the ISE check will be explained using Figure 8. The graph in Figure 8 shows the ion concentration of the liquid to be measured on the horizontal axis and the electromotive force measured when the liquid to be measured is measured with an ion selective electrode on the vertical axis. The slope sensitivity mentioned above indicates the gradient of the electromotive force change relative to the concentration change. Based on this slope sensitivity, the concentration of the internal standard solution can be calculated from the electromotive force measured when the internal standard solution is measured with the ion selective electrode.

[0042] In Figure 8, the calculated concentration is shown as A. On the other hand, the concentration of the original internal standard solution is known as B. If the difference between A and B is within a predetermined range, it is judged to be normal, and if it is outside the range, an alarm is issued. This is the ISE check. Figure 8 shows an example of Na ＋ The slope sensitivity is shown, but similar slope sensitivity is also created for potassium ions and chloride ions.

[0043] Next, the operation during continuous analysis (general sample analysis) will be described using the flow diagram shown in Figure 2B. After the calibration operation, analysis is performed using serum, urine, or other samples. In the processing flow shown in Figure 2B, step S203 in Figure 2A includes detailed operations as explained in the flow diagram shown in Figure 3, but for simplicity of explanation, detailed descriptions of the operations will be omitted.

[0044] Specifically, the specimen contained in the specimen container 1 is dispensed into the dilution tank 120 by the specimen dispensing nozzle 2, and then the diluent in the diluent bottle 151 is dispensed into the dilution tank 120 using the diluent syringe pump 132 to dilute the specimen at a set ratio D. During this time, the reference electrode solution is introduced from the reference electrode solution bottle 161 into the flow path of the reference electrode 104. The diluted specimen in the dilution tank 120 is sucked through the sipper nozzle 107 and introduced into the flow path of each electrode of the ion selective electrode 110.

[0045] The reference electrode solution and the diluted sample come into contact at the liquid junction. The potential difference (electromotive force) between the ion selective electrode 110 and the reference electrode 104 is measured by the potential measuring unit 171 (S211). The vacuum pump 112 is operated to suck up the remaining liquid in the dilution tank 120 using the vacuum suction nozzle 106 and discard it in the waste liquid tank 111, and then the internal standard solution in the internal standard solution bottle 141 is dispensed into the dilution tank 120. Meanwhile, the sipper syringe pump 133 is operated to discard the liquid remaining in the flow path of the reference electrode 104 into the waste liquid tank 111, and the reference electrode solution is introduced from the reference electrode solution bottle 161 into the flow path of the reference electrode 104.

[0046] Next, the internal standard solution in the dilution tank 120 is sucked from the sipper nozzle 107, and the electromotive force of each electrode is measured by the potential measuring unit 171 while the flow path of the ion selective electrode 110 is filled with the internal standard solution (S212). Thereafter, the liquid remaining in the dilution tank 120 is sucked up by the vacuum suction nozzle 106 and disposed of in the waste liquid tank 111.

[0047] The concentration of the sample is calculated using the following formula from the slope sensitivity determined in S203 and the concentration of the internal standard calculated in S204 (S213). (C) Sample Concentration CS = CIS x 10b (Formula 4) b = (EMFIS - EMFS) / SL (Formula 5) CS: Sample concentration EMFS: Measured electromotive force of the sample Note that the above formulas are basic, and various corrections such as for temperature drift and carryover may be added. Also, refreshing liquid may be introduced into the dilution tank or flow path during the analysis.

[0048] If the user replaces either the electrode of the ion selective electrode 110 or the reference electrode 104 between analyses, the electrode replacement detection mechanism (not shown) detects that the electrode has been replaced (S214) and performs the calibration operation described above.

[0049] If the electrode has not been replaced, it is next determined whether the amount of internal standard solution is sufficient (S215), and if it is not sufficient, an alarm is issued (S216). If this alarm is issued, the system operator removes the bottle of internal standard solution with the lowest remaining amount before the remaining amount reaches zero, and installs the next bottle of internal standard solution.

[0050] If the internal standard bottle needs to be replaced, the process proceeds to the internal standard bottle replacement flow shown in the flow diagram of Fig. 2C. In the process flow shown in Fig. 2C, step S203 in Fig. 2A includes detailed operations as explained in the flow diagram shown in Fig. 3, but for simplicity of explanation, detailed operations will be omitted.

[0051] First, before replacing the internal standard bottle, the internal standard solution in the internal standard bottle 141 currently in use is dispensed into the dilution tank 120. During this time, the reference electrode solution is introduced from the reference electrode solution bottle 161 into the flow path of the reference electrode 104. The internal standard solution in the dilution tank 120 is sucked through the sipper nozzle 107, and with the flow path of the ion selective electrode 110 filled with the internal standard solution, the potential difference (electromotive force) between each electrode of the ion selective electrode 110 and the reference electrode 104 is measured by the potential measuring unit 171 (S231).

[0052] Next, the vacuum pump 112 is operated to suck up the remaining liquid in the dilution tank with the vacuum suction nozzle 106 and discard it in the waste liquid tank 111. Next, the system operator starts to supply internal standard solution from the new internal standard solution bottle replaced by the system operator (S232), replacing the liquid in the supply flow path (S233). Thereafter, the internal standard solution in the new bottle is dispensed into the dilution tank. Meanwhile, the reference electrode solution is introduced from the reference electrode solution bottle into the flow path of the reference electrode 104.

[0053] Next, the internal standard solution in the dilution tank is sucked from the sipper nozzle 107, and the potential difference (electromotive force) between each electrode of the ion selective electrode 110 and the reference electrode 104 is measured by the potential measuring unit 171 with the flow path of the ion selective electrode 110 filled with the internal standard solution (S234). The remaining liquid in the dilution tank 120 is sucked up by the vacuum suction nozzle 106 and discarded in the waste liquid tank 111.

[0054] Next, the control unit 175 calculates the concentration value of the internal standard solution using the following formula, determines whether the concentration is abnormal (whether it is within a preset normal range), and if it is within the normal range, corrects the concentration value of the internal standard solution (S235). The value calculated using formula (Formula 1) is used as the slope sensitivity SL. (D) Internal Standard Solution Concentration Correction CIS' = CIS x 10c (Formula 6) c = (EMFIS' - EMFIS) / SL (Formula 7) CIS: Concentration of the internal standard solution in the current bottle CIS': Concentration of the internal standard solution in the new bottle EMFIS: Electromotive force of the internal standard solution in the current bottle EMFIS': Electromotive force of the internal standard solution in the new bottle The correction of concentration values ​​will be explained using Figure 9. If there is a difference between the electromotive force C (EMFIS) of the internal standard solution in the current bottle and the electromotive force D (EMFIS') of the internal standard solution in the new bottle, the slope sensitivity is shifted by the amount of the difference (in the case of Figure 9, the slope sensitivity is shifted downward). The shifted slope sensitivity is used as the new slope sensitivity, and the ion concentration is calculated based on the electromotive force measured for the general sample. Note that Figure 9 also shows the slope sensitivity of sodium ions as an example, as in Figure 8. Then, continuous analysis is automatically resumed.

[0055] This concentration correction allows for accurate correction because the reagent (internal standard solution) after switching is measured using the ion selective electrode itself used for analyzing the sample.

[0056] The concentration correction can also be calculated from the slope sensitivity during calibration and the electromotive force value when measuring a standard solution of known concentration. Furthermore, the reagent may not only be an internal standard solution containing three ions of known concentration (chlorine, sodium, and potassium), but also an internal standard solution containing one type of each ion may be used for measurement.

[0057] This device measures and corrects the reagent concentration appropriately when switching between reagent containers, so even if there is a slight error in concentration adjustment when switching, the analysis value will not deviate. As a result, this flow-type electrolyte concentration measurement device can absorb slight concentration errors that occur between reagent bottles, reducing the burden on the operator and downtime of the device. This concludes the description of the electrolyte concentration measurement device described in Patent Document 1, to which the present invention is applicable.

[0058] Hereinafter, an embodiment of the present invention will be described with reference to the drawings. In all drawings for explaining the embodiment, components having the same functions are assigned the same reference numerals, and repeated explanations thereof will be omitted as a general rule.

[0059] However, the present invention should not be construed as being limited to the description of the embodiments shown below. Those skilled in the art will readily understand that the specific configurations can be modified without departing from the spirit or intent of the present invention.

[0060] 4A is a diagram showing the details of steps S231 to S234 in FIG. 2C in the technology described in Patent Document 1. The internal standard solution supply nozzle dispenses the internal standard solution into the dilution tank, the sipper nozzle descends into the dilution tank, the internal standard solution in the dilution tank is drawn into the ion-selective electrode, and the electromotive force is measured. After the measurement is completed, the vacuum suction nozzle sucks and discharges the remaining liquid in the dilution tank.

[0061] Furthermore, a new internal standard solution bottle is installed so that the instrument operator can aspirate the internal standard solution from the new bottle, and the liquid in the flow path leading to the ion-selective electrode is replaced with the new internal standard solution. The internal standard solution is dispensed from the new bottle into the dilution tank (dilution cup), the sipper nozzle descends into the dilution tank, the internal standard solution in the dilution tank is drawn into the ion-selective electrode, and the electromotive force is measured. Measurement of the internal standard solution is performed multiple times to account for variations in measurement values. In this example, 10 measurements are performed. Because the same internal standard solution is measured, carryover prevention cleaning (cleaning the dilution tank to prevent different samples from mixing via the dilution tank) is not performed after each measurement, as is the case with measurements of general samples, and measurements are performed continuously.

[0062] After the measurement is completed, the dilution tank is cleaned by discharging the dilution liquid (cleaning liquid) into the dilution tank, and the remaining liquid in the dilution tank is sucked out by the vacuum suction nozzle. The number of measurements does not have to be 10 times. It can be set appropriately within the range of 5 to 30 times based on the measurement time, the required accuracy of the ISE check, etc. Generally, 10 to 20 times is preferable.

[0063] In contrast, the process of the present invention is shown in Figure 4B. The process up to "discharging the internal standard solution from the new bottle into the dilution cup" is the same as Figure 4A. After measuring the electromotive force of the internal standard solution, the dilution solution is discharged into the dilution cup to clean it, and then the remaining liquid in the dilution cup is sucked with a vacuum suction nozzle, the internal standard solution is discharged from the new bottle into the dilution cup, the internal standard solution is discharged into the dilution tank by a supply nozzle, and the electromotive force is measured.

[0064] The difference from Figure 4A is that after measuring the electromotive force with the ion selective electrode, the dilution solution for washing is dispensed into the dilution cup, the remaining liquid is drained, and then the internal standard solution is dispensed into the dilution cup... This process is repeated 10 times.

[0065] When measuring different general samples, it is common to wash the dilution cup to avoid contamination, but when measuring the same sample repeatedly, there is no need to avoid contamination, so the dilution cup is not washed after each measurement. Similarly, when measuring the same internal standard solution 10 times consecutively, the dilution cup washing step is unnecessary, as shown in Figure 4A, and it is common sense for engineers to omit it.

[0066] However, the inventors have newly discovered that even when consecutively measuring the same internal standard solution, washing the dilution cup between measurements, as with measurements of different general samples, is effective in preventing high measurement values. The liquid used for the washing operation is typically a dilution solution (reagent) or system water, but the internal standard solution may also be diluted with the dilution solution or system water. Although the term "washing operation" is used here for explanatory purposes, it is not limited to washing. For example, pouring a liquid into the dilution cup can cool or warm it, bringing it to a state similar to that of the dilution cup when measuring general samples. In other words, the use of a liquid different from the internal standard solution used in electrolyte measurements for ISE checks is also included in the "washing operation" referred to here.

[0067] FIG. 5A shows the QC (Quality Control) measurement results, which indicate the variation in the measurement results of a sample (quality control sample) with a known concentration, obtained using the process shown in FIG. 4A of Patent Document 1. Here, the first 10 measurements were taken using QC1 (quality control sample 1), the next 10 measurements were taken using QC2 (quality control sample 2), the next 10 measurements were taken using QC1, and the final 10 measurements were taken using QC2. The internal standard solution bottle was replaced after the first 20 measurements. It can be seen that the QC measurement values ​​after the internal standard solution bottle replacement tended to be higher overall.

[0068] In contrast, the results of measurements made in the same manner as above using the process shown in Figure 4B are shown in Figure 5B. In this case too, the bottle of internal standard solution was replaced after the first 20 measurements, but it is clear that there is no difference in the measurements between the first and second halves, even when compared to Figure 5A.

[0069] That is, by using the process of FIG. 4B according to the present invention, even when the bottle containing the internal standard solution is replaced, it is possible to obtain highly reliable measurement results without performing calibration by correcting the calibration curve based on the difference between the measurement results of the internal standard solution before and after replacement.

[0070] At present, it is not clear why such results are obtained by using the process shown in Figure 4B. There are two current hypotheses: either the discharge of dilution liquid into the dilution tank that discharges the internal standard liquid can prevent the temperature of the dilution tank from dropping, or the discharged dilution liquid remains in the dilution tank, diluting the internal standard liquid and preventing high measurement values.

[0071] FIG. 6 shows a modified example of the electrolyte analyzer shown in FIG. 1, in which the mixture of the specimen and dilution solution and the standard solution are drawn from a container separate from the container that draws the standard solution.

[0072] Here, the sample and diluent are dispensed into a reaction cell 302 using a sample dispensing probe 307. An internal standard solution 308 is dispensed into a container 303 (corresponding to dilution tank 120 in FIG. 1) that is different from the reaction cell 302. The internal standard solution is dispensed by operating a syringe 304, as in FIG. 1. After measurement, waste liquid is discharged from the container 303 by operating a syringe 305.

[0073] The ISE electrode is built into the suction unit 301, which is equipped with a suction tube 310. The suction unit 301, which is equipped with the ISE electrode and suction tube, can physically move (left and right in FIG. 6) and move between containers from which the liquid to be sucked is being discharged. Suction in the suction unit 301 is performed by operating a syringe 306. Information on the potential measured by the ISE electrode is sent via a signal line to a signal processing unit 8, which calculates the ion concentration. The effects of the present invention can be achieved even with the configuration shown in FIG. 6.

[0074] FIG. 7 is also a modified example of the electrolyte analyzer shown in FIG. 1, in which the liquid to be measured flows from the bottom of the container that receives the specimen, diluent, and standard solution to the ISE measurement section.

[0075] Here, a hole is opened in the dilution tank (510), and by switching the solenoid valve 500, the liquid in the dilution tank (510) can be drawn into the ion selective electrode (110). A detailed description of the device configuration will be omitted.

[0076] Fig. 11 is a schematic diagram of an electrolyte measuring device described in Patent Document 1. The biggest difference from the automatic analyzer of Fig. 1 according to the present invention is that two bottles each of the internal standard solution (IS), diluent solution (DIL), and reference solution (REF) can be placed on the device.

[0077] By switching the flow path switching valves 126, 127, and 128, the bottle to be used can be switched, and an empty bottle can be easily replaced.

[0078] It goes without saying that the present invention can be applied to the device shown in Fig. 11. For details of the device configuration, please refer to Patent Document 1.

[0079] 100...flow type electrolyte concentration measuring device, 104...comparison electrode, 106...vacuum suction nozzle, 107...sipper nozzle, 108...dilution solution supply nozzle, 109...internal standard solution supply nozzle, 110...ion selective electrode, 111...waste tank, 112...vacuum pump, 131...syringe pump for internal standard solution, 132...syringe pump for dilution solution, 133...sipper syringe pump, 141...internal standard solution bottle, 151...dilution solution bottle, 161...comparison electrode solution bottle, 171...potential measuring unit, 174...display unit, 175...control unit, 176...input unit.

Claims

1. An automated analyzer equipped with a measuring unit for measuring the electrolyte concentration of a sample, The measurement unit includes an ion-selective electrode for measuring the electromotive force of the target ions contained in the sample, a dilution tank for diluting the sample, and a channel for introducing the sample diluted in the dilution tank into the ion-selective electrode. An automated analyzer characterized in that, even when the same internal standard sample is measured multiple times in a row in the measurement unit, the control unit controls the measurement to perform the same internal standard sample measurement multiple times in a row, after performing a measurement preparation operation similar to that for measuring a sample, which includes at least a cleaning step of cleaning the dilution tank with a cleaning solution, before each of the multiple measurements of the same internal standard sample.

2. In the automated analyzer according to claim 1, The automated analyzer is characterized in that the cleaning step is a step of supplying a liquid different from the internal standard sample to the measuring unit, which includes a liquid obtained by mixing the internal standard sample with another liquid.

3. In the automated analyzer according to claim 1, An automated analyzer characterized by having a display unit that displays the measurement results of the internal standard sample along with preset lower and upper limits.

4. In the automated analyzer according to claim 1, The system includes a concentration calculation unit that defines a formula for calculating the concentration of a sample based on the measurement results of at least two standard samples with different electrolyte concentrations, the electrolyte concentrations of which are known in advance. The automatic analyzer is characterized in that the concentration calculation unit corrects the calculation formula based on the electrolyte concentration measurement result of the internal standard sample, and calculates the concentration of the sample using the corrected calculation formula.

5. In the automated analyzer according to claim 4, An automated analyzer characterized in that the timing of measuring the electrolyte concentration of the internal standard sample for correcting the calculation formula is at least the timing that triggers the replacement of the bottle containing the internal standard sample.

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7. (delete)

8. In the automated analyzer according to any one of claims 1 to 5, An automated analyzer characterized by comprising a transfer mechanism for moving a channel introduced into the ion-selective electrode and the ion-selective electrode between a reaction vessel for performing colorimetric measurement of the sample and the dilution tank.

9. In the automated analyzer according to any one of claims 1 to 5, The automated analyzer is characterized in that the ion-selective electrode is provided in the middle of a flow path that directly or indirectly connects the dilution tank and the waste section for discarding the liquid in the dilution tank.

10. In the automated analyzer according to any one of claims 1 to 5, An automated analyzer characterized by comprising a mounting mechanism for mounting multiple containers for containing the internal standard sample, and a switching mechanism for supplying the internal standard sample to the measuring unit from any one of the multiple containers.

11. An electrolyte measurement method for an automated analyzer equipped with a measuring unit for measuring the electrolyte concentration of a sample, The measurement unit includes an ion-selective electrode for measuring the electromotive force of the target ions contained in the sample, a dilution tank for diluting the sample, and a channel for introducing the sample diluted in the dilution tank into the ion-selective electrode. An electrolyte measurement method for an automated analyzer, characterized in that, even when measuring the same internal standard sample multiple times consecutively in the measurement unit, a measurement preparation operation similar to that for measuring a sample sample, including at least a cleaning step of cleaning the dilution tank with a cleaning solution, is performed before each of the multiple measurements of the same internal standard sample, and then the measurement of the same internal standard sample is performed multiple times consecutively.

12. In the electrolyte measurement method of the automated analyzer according to claim 11, The system includes a concentration calculation unit that defines a formula for calculating the concentration of a sample based on the measurement results of at least two standard samples with different electrolyte concentrations, the electrolyte concentrations of which are known in advance. An electrolyte measurement method for an automated analyzer, characterized by correcting the calculation formula based on the electrolyte concentration measurement results of the internal standard sample, and calculating the concentration of the sample using the corrected calculation formula.

13. In the electrolyte measurement method of the automated analyzer according to claim 12, An electrolyte measurement method for an automated analyzer, characterized in that the timing of measuring the electrolyte concentration of the internal standard sample for correcting the calculation formula is at least the timing that triggers the replacement of the bottle containing the internal standard sample.

14. (delete)

15. (delete)

16. In the method for measuring electrolytes in an automated analyzer according to any one of claims 11 to 13, An electrolyte measurement method for an automated analyzer, characterized in that the flow channel introduced to the ion-selective electrode and the ion-selective electrode are moved between a reaction vessel for performing colorimetric measurement of the sample and the dilution tank to perform the measurement.