阅读说明：本技术 电解质浓度测量装置 (Electrolyte concentration measuring device ) 是由 岸冈淳史 小野哲义 于 2019-09-02 设计创作，主要内容包括：一种电解质浓度测量装置,其具备：被供给液体的离子选择性电极；作为电位的基准的参比电极；取得离子选择性电极的电位的电位测量部；根据由电位测量部取得的电位,计算液体中所包含的离子的浓度的浓度算出部；持续监测离子选择性电极的电位而生成电位响应曲线的电位监测部；取得关于各种动作的时机的时机信号的时机信号取得部；基于电位响应曲线和时机信号的关联性,检测装置的异常预兆的电位响应曲线分析部。(An electrolyte concentration measuring device is provided with: an ion selective electrode to which liquid is supplied; a reference electrode as a reference of the potential; a potential measuring unit for obtaining a potential of the ion selective electrode; a concentration calculating unit for calculating the concentration of ions contained in the liquid based on the potential obtained by the potential measuring unit; a potential monitoring unit for continuously monitoring the potential of the ion selective electrode to generate a potential response curve; a timing signal acquisition unit for acquiring timing signals related to timings of various operations; and a potential response curve analysis unit for detecting a sign of abnormality of the device based on the correlation between the potential response curve and the timing signal.)

1. An electrolyte concentration measuring device for measuring the concentration of ions in a liquid, comprising:

an ion selective electrode supplied with the liquid;

a reference electrode as a reference of the potential;

a potential measuring unit for obtaining a potential of the ion selective electrode;

a concentration calculating unit that calculates a concentration of ions contained in the liquid based on the potential obtained by the potential measuring unit;

a potential monitoring unit for monitoring a potential of the ion selective electrode to generate a potential response curve;

a timing signal acquisition unit for acquiring timing signals related to timings of various operations;

and a potential response curve analysis unit for detecting a sign of abnormality of the device based on the correlation between the potential response curve and the timing signal.

2. The electrolyte concentration measurement device according to claim 1, wherein the potential response curve analysis unit calculates a feature amount of the potential response curve at a timing at which the timing signal is obtained, and follows a sign of abnormality of the feature amount detection device.

3. The electrolyte concentration measurement device according to claim 2, wherein the potential response curve analysis unit has library data regarding a characteristic amount of the potential response curve, and compares the characteristic amount of the library data with the characteristic amount of the potential response curve to detect a sign of abnormality of the device.

4. The electrolyte concentration measurement apparatus according to claim 1, wherein the potential response curve analysis unit determines a sign of deterioration of the mechanism unit and a change in physical properties of the electrode based on waveforms of the potential response curve at and immediately after an operation of the mechanism unit.

5. The electrolyte concentration measurement device according to claim 1, wherein the potential response curve analysis unit determines contamination of the surface of the ion sensitive membrane of the ion selective electrode based on a waveform of a potential response curve when an operation of the mechanism unit related to movement of the liquid in the liquid flow path is stopped.

6. The electrolyte concentration measurement device according to claim 1, further comprising a sensor for detecting a behavior in the device,

the potential response curve analysis unit detects a sign of abnormality based on a correlation between the potential response curve, the timing signal, and the detection signal of the sensor.

Technical Field

The present invention relates to an electrolyte concentration measuring apparatus that measures the concentration of an electrolyte in a liquid.

Background

An automatic analyzer is known as an apparatus for analyzing a sample containing protein contained in a sample such as blood or urine with high accuracy and high throughput. Many electrolyte concentration measuring devices are mounted on such automatic analyzers, but there are also composite measuring devices with blood gas and the like, single-body machines of electrolyte concentration measuring devices, and the like. The electrolyte concentration measuring device is configured to analyze electrolyte components such as sodium (Na) ions, potassium (K) ions, and chlorine (Cl) ions in a sample, for example.

Such an electrolyte concentration measuring apparatus mostly uses a method called an ion selective electrode method (ISE method). The ISE method measures the electrolyte concentration in a sample by measuring the potential difference between an ion selective electrode (ISE electrode) and a reference electrode that generates a reference potential. The ion selective electrode includes an ion sensitive membrane that generates a potential difference in response to an ion component. Typically, these electrodes are consumable, e.g., 2-3 months or thousands of tests achieve a useful life, being replaced with new electrodes.

In addition, several kinds of reagents are conventionally used in an electrolyte concentration measuring apparatus. The type of reagent used varies depending on the configuration of the apparatus, and examples thereof include an internal standard solution, a diluent for diluting a sample, and a reference electrode solution supplied to a reference electrode to form a liquid junction with the sample solution.

In an electrolyte concentration measuring apparatus, calibration is performed using a standard solution having a known concentration at the time of starting the apparatus, at the time of replacing an electrode, or at the time of replacing a reagent bottle, and a calibration curve is prepared. In this manner, the accuracy of analysis is ensured by periodically performing calibration.

On the other hand, as a method of determining a sign of abnormality of an electrode and a device, a method of determining a sign of abnormality based on the results of calibration performed at the time of starting the device and at the time of replacing the electrode and the reagent is generally known. For example, patent document 1 discloses a technique of calculating a prediction of a performance life (replacement timing) of an electrode based on information stored in an information table in order to manage the electrode from the time of manufacture to the time of service life, wherein the information table includes a type of ion to be measured, a term of validity after manufacture of the electrode, a number of days of use of a current user of the electrode, a number of measurement samples of the electrode, a sensitivity of the electrode (latest sensitivity measurement result), a precision of the electrode (latest precision measurement result), and a potential of the electrode (latest potential measurement result), and a formula and a judgment standard preset on a manufacturer side or a user side.

Further, as a technique for determining whether or not a measured value is normal, unlike a sign of abnormality of an electrode or a device, patent document 2 discloses a technique in which when potential data from the suction of a sample liquid until the potential is stabilized deviates from an allowable range calculated from a value of a potential difference of the sample liquid before and after the suction, it is determined that analysis data of the sample after the suction is abnormal.

Prior art documents

Patent document

Patent document 1: japanese patent laid-open publication No. 2004-

Patent document 2: japanese patent laid-open No. 2012 and 42359

In order to achieve continuous operation for 24 hours and an increase in analysis throughput in an electrolyte concentration measuring device, it is necessary to constantly perform stable operation of the device, that is, to increase the operation rate of the device. To achieve this, it is important to calibrate the frequency and maintain the appropriation of the frequency.

In a conventional electrolyte concentration measuring apparatus, calibration is performed at a relatively high frequency such as once every several hours in order to maintain high measurement accuracy. Since the frequency of scaling becomes high and this hinders the improvement of the operation rate of the device, it is required to increase the scaling interval (decrease the frequency). In this case, it is important to constantly monitor the electrode and device for large changes in condition at the calibrated gap.

In the conventional apparatus, the timing of replacing various elements and electrodes is determined based on a set period and the number of samples to be analyzed. Further, the inclination (slope) of the calibration curve, the electromotive force, the change in measurement reproducibility, and the like are also considered as judgment materials in the judgment of the timing of replacement. In this way, when an abnormality is found in the apparatus at the time of calibration, it is necessary to stop the apparatus, identify the cause of the abnormality, prepare for replacement of the component, perform the replacement operation, and perform the calibration again. In the meantime, the operator is also restrained for a long time, which becomes down time of the apparatus, and a substantial flux is reduced.

If the sign of such an abnormality can be grasped in advance, the maintenance schedule can be made while the apparatus is operated without stopping the apparatus. However, the performance deterioration due to the contamination of the surface of the sensing film of the ion selective electrode, the peeling of the film, and the like, and the slow leakage of the solenoid valve, and the like do not appear as significant abnormalities in the measurement potential of the ion selective electrode. Therefore, it is difficult to accurately detect the signs of these abnormalities.

Disclosure of Invention

An object of the present invention is to provide an electrolyte concentration measuring device capable of accurately detecting various signs of abnormality of the device even when the device is operated, optimizing a maintenance frequency and a calibration frequency, and improving a substantial flux.

An electrolyte concentration measuring device according to the present invention is an electrolyte concentration measuring device that measures a concentration of ions in a liquid, and includes: an ion selective electrode supplied with the liquid; a reference electrode as a reference of the potential; a potential measuring unit for obtaining a potential of the ion selective electrode; a concentration calculation unit that calculates a concentration of ions contained in the liquid based on the potential obtained by the potential measurement unit; a potential monitoring unit for monitoring a potential of the ion selective electrode to generate a potential response curve; a timing signal acquisition unit for acquiring timing signals related to timings of various operations; and a potential response curve analysis unit for detecting a sign of abnormality of the device based on the correlation between the potential response curve and the timing signal.

According to the present invention, it is possible to provide an electrolyte concentration measuring apparatus capable of accurately detecting various signs of abnormality of the apparatus even when the apparatus is operated, optimizing the maintenance frequency and the calibration frequency, and improving the substantial flux.

Drawings

Fig. 1 is a schematic diagram showing an example of a flow-type electrolyte concentration measuring apparatus 10 according to a first embodiment.

Fig. 2 is a flowchart illustrating a measurement procedure of the electrolyte concentration measurement device of the first embodiment.

Fig. 3 is an example of a graph of a potential response curve obtained by the potential monitoring unit 181.

Fig. 4 is an enlarged view of a portion of the potential response curve of the measurement section a acquired by the potential monitoring unit 181 of the first embodiment, and a conceptual diagram in which timing signals acquired by the timing signal acquisition unit 182 are superimposed.

Fig. 5 is a conceptual diagram specifically illustrating a method of monitoring the potential of the sodium ion electrode 101C and determining a sign of an abnormality.

Fig. 6 is a conceptual diagram specifically illustrating a method of monitoring the potential of the chloride ion electrode 101A and determining a sign of an abnormality.

Fig. 7 is a schematic diagram showing an example of the flow-type electrolyte concentration measuring apparatus 10 according to the second embodiment.

Fig. 8 is a conceptual diagram in which an enlarged view of a portion of the potential response curve of the measurement section a acquired by the potential monitoring unit 181 of the second embodiment and a timing signal acquired by the timing signal acquisition unit 182 are superimposed and displayed.

Detailed Description

The present embodiment will be described below with reference to the drawings. In the drawings, functionally identical elements may be denoted by the same reference numerals. Also, the drawings show embodiments and examples in accordance with the principles of the present disclosure, but these are for understanding the present disclosure and are not to be construed as limiting the present disclosure in any way. The description of the present specification is merely a representative example, and does not limit the scope or application of the claims of the present disclosure in any way.

In the present embodiment, the present disclosure has been described in detail with respect to the implementation of the present disclosure by a practitioner, but it is to be understood that other mounting and form may be adopted, and that changes in the configuration and structure and replacement of various elements may be made without departing from the scope and spirit of the technical idea of the present disclosure. Therefore, the following description is not to be construed as limiting.

[ first embodiment ]

An electrolyte concentration measurement device 10 according to a first embodiment is described with reference to fig. 1 to 6. Fig. 1 is a schematic diagram showing an example of a flow-type electrolyte concentration measuring apparatus 10 according to a first embodiment. The electrolyte concentration measuring apparatus 10 is roughly composed of a measuring unit 100 and an arithmetic and control unit 200. The electrolyte concentration measuring apparatus 10 is configured to measure the potential difference between the electrodes by alternately performing measurement of the sample and measurement of the internal standard solution, and to measure the concentration of the specific ion in the sample using the potential difference and the calibration line. The electrolyte concentration measuring apparatus 10 is configured to detect abnormalities of the apparatus, such as physical deterioration of the electrodes and the like, slow leakage of the solenoid valve, and the like, based on a timing signal indicating a predetermined operation and a potential response curve indicating a potential change, as will be described later.

The measurement unit 100 includes: an ion selective electrode 101, a reference electrode 102, a pinch valve 103, a dilution tank 104, an internal standard solution syringe pump 105, a diluent syringe pump 106, a pipette syringe pump 107, an internal standard solution bottle 108, a diluent solution bottle 109, a reference electrode solution bottle 110, a waste liquid barrel 111 and a vacuum pump 112.

The ion-selective electrode 101 includes, for example, a chloride ion electrode 101A, a potassium ion electrode 101B, and a sodium ion electrode 101C. As described later, the ion selective electrode 101 is supplied with a sample solution (diluted sample solution) or an internal standard solution, which is mixed with the diluent, from the dilution tank 104 through the pipette nozzle N0. The reference electrode 102 is supplied with a reference electrode liquid as described later. The reference electrode solution is stored in the reference electrode solution bottle 110 and is discharged to the reference electrode 102 through a flow path suitably provided with an electromagnetic valve V1. In the following description, the chloride ion electrode 101A, the potassium ion electrode 101B, and the sodium ion electrode 101C may be collectively referred to as "ion-selective electrodes 101A to 101C".

The pinch valve 103 switches between opening and closing of a flow path connecting the ion-selective electrode 101 and the reference electrode 102.

The dilution tank 104 is filled with a sample solution or an internal standard solution diluted with a diluent. The internal standard solution syringe pump 105 is a pump for ejecting the internal standard solution toward the dilution well 104. The internal standard solution is stored in an internal standard solution bottle 108, and is discharged to the dilution well 104 by an internal standard solution syringe pump 105. Further, an electromagnetic valve V2 was provided in a flow path connecting the internal standard solution bottle 108 and the internal standard solution syringe pump 105, and an electromagnetic valve V3 was provided in the internal standard solution nozzle N1. At the time of ejection of the internal standard liquid, the solenoid valves V2 and V3 were opened. The internal standard solution nozzle N1 may be provided with a preheater (not shown) for heating the internal standard solution.

The diluent syringe pump 106 is a pump for discharging the diluent toward the dilution tank 104. The diluent is stored in a diluent bottle 109 and discharged to the dilution tank 104 by a diluent syringe pump 106. Further, an electromagnetic valve V4 is provided in a flow path connecting the diluent bottle 109 and the diluent syringe pump 106, and an electromagnetic valve V5 is provided in the pipette nozzle N2. The straw nozzle N2 may be provided with a preheater (not shown) for heating the diluent. The nozzle N1 for the internal standard liquid and the pipette nozzle N2 may be configured to be insertable into and removable from the dilution tank 104 as needed.

The pipette syringe pump 107 is a pump that operates when the sample liquid or the like is sucked from the dilution tank 104 to the ion-selective electrode 101 side. When the pipette syringe pump 107 performs a suction operation on the sample liquid or the like, the pinch valve 103 is also opened. The sample liquid sucked by the pipette syringe pump 107 is introduced as a waste liquid into the waste liquid tank 111 and discarded.

The pipette syringe pump 107 operates also when the reference electrode solution is sucked toward the reference electrode 102 and when the reference electrode solution is sucked from the reference electrode 102 and discarded. At this time, the electromagnetic valve V8 of the flow path between the reference electrode 102 and the pipette syringe pump 107 and the electromagnetic valve V7 between the pipette syringe pump 107 and the waste liquid tank 111 are opened, and the pinch valve 103 is closed. The vacuum pump 112 operates when discharging the waste liquid from the waste liquid tank 111 to the outside.

When the sample solution or the like is injected into the ion-selective electrode 101 and the reference electrode 102 is injected into the reference electrode solution in this manner, a potential difference between the ion-selective electrode 101 and the reference electrode 102 is generated. This potential difference changes according to the ion concentration to be analyzed of the liquid introduced into the flow path of the ion-selective electrode 101. Therefore, by measuring the potential difference, the concentration of the ions (for example, Cl, K, and Na) to be analyzed in the solution can be calculated.

On the other hand, the arithmetic control unit 200 includes: a potential measuring unit 171; a concentration calculation unit 172; an output section 174; the device control section 175; an input section 176; a potential monitoring unit 181; a timing signal acquisition unit 182; a potential response curve analysis unit 183; and a data storage section 184.

The potential measuring unit 171 has a function of measuring potential differences (electromotive forces) between the ion-selective electrodes 101A to 101C and the reference electrode 102. More specifically, the potential measuring unit 171 has a function of measuring a stable potential after a certain time has elapsed after the liquid is introduced into the flow path of the ion-selective electrodes 101A to 101C. A concentration calculating section 172 for calculating specific ions (Cl) in the diluted sample solution or the internal standard solution based on the potential difference calculated by the potential measuring section 171^－、K⁺、Na⁺) The concentration of (c). The output unit 174 includes a display or the like for outputting the calculation result of the density calculation unit 172. The device control unit 175 controls the measurement unit 100. The input unit 176 is an interface for inputting various data and commands to the device control unit 175.

The potential monitoring unit 181 continuously monitors the potentials of the ion-selective electrodes 101A to 101C, and generates a potential response curve indicating a temporal change in the monitored potentials. More specifically, the potential monitoring unit 181 has a function of monitoring a transient change in potential (potential response curve) from the introduction of the liquid into the flow path of the ion-selective electrodes 101A to 101C to the discharge. Here, "transient" means a temporary change in potential caused by actual operations of various elements, a flow of liquid in a pipe, diffusion of a substance or liquid, or the like, unlike timing for obtaining a stable measurement potential. The timing signal acquisition unit 182 acquires various timing signals output from the device control unit 175 to the measurement unit 100.

The potential response curve analyzing unit 183 has a function of analyzing the potential response curve generated by the potential monitoring unit 181. The potential response curve analyzing unit 183 also acquires the timing signal from the timing signal acquiring unit 182, and correlates the timing signal with the potential response curve. More specifically, the potential response curve analysis unit 183 determines the sign of the physical change of the electrode and the deterioration of the various mechanism units based on the waveforms of the potential response curves during and immediately after the operation of the various mechanism units. The potential response curve analysis unit 183 determines contamination of the surface of the ion sensitive membrane of the ion selective electrode 101 based on the waveform of the potential response curve at the time of operation stop of the various mechanism units related to the movement of the liquid in the liquid flow path.

The reference electrode solution introduced into the flow path of the reference electrode 102 and the diluted sample solution (or internal standard solution) introduced into the ion-selective electrode 101 are brought into contact with each other at the liquid junction 120 to form a liquid junction. The liquid junction electrically connects the ion-selective electrode 101 and the reference electrode 102. At this time, the potential difference (electromotive force) between each ion selective electrode 101 and the reference electrode 102 changes depending on the concentration of the analyte ions in the diluted sample solution (or the internal standard solution) introduced into the flow path of the ion selective electrode 101. This electromotive force can be measured by the potential measuring unit 171, and the ion concentration can be calculated by the concentration calculating unit 172. Details of the calculation method will be described later.

Next, the procedure of measurement in the electrolyte concentration device of the first embodiment will be described with reference to the flowchart of fig. 2. In fig. 2, (a) shows a step at the time of starting the apparatus, and (b) shows a step at the time of alternately and continuously measuring the sample and the internal standard liquid ("continuous analysis") after the apparatus is started.

First, the procedure at the time of device activation will be described with reference to fig. 2 (a). First, the apparatus 10 is started by turning on a power supply (not shown) (step S201), and the reagent bottles 108, 109, and 110 are set (step S202). Thereafter, the reagent in the reagent bottle is initially filled in the apparatus 10 (reagent filling) (step S203).

After the temperature adjustment is completed, the internal standard solution is continuously measured (step S204), and it is confirmed that the potential of the electrode is stable. Next, in order to determine calibration curves of the ion-selective electrodes 101A to 101C, two kinds of standard solutions of known concentrations (high concentration (H) and low concentration (L)) were measured, and the slope sensitivity SL of the calibration curves was calculated (step S205). Next, the concentration Cis of the internal standard solution is calculated based on the slope sensitivity SL obtained in step S205 and the measured electromotive force (step S206).

In the various operations in the above-described steps S201 to S206, timing signals for operating the various pumps 105 to 107, the solenoid valves, and other various driving units in the electrolyte concentration measuring apparatus 10 are output from the apparatus control unit 175. The timing signal is acquired by the timing signal acquisition unit 182. In steps S201 to S206, the potentials of the ion-selective electrodes 101A to 101C fluctuate, and the fluctuation is monitored by the potential monitoring unit 181. The data of the monitored potential is also sent to the timing signal acquisition unit 182, and is associated with the timing signal and subjected to data processing. The potential response curve analyzing unit 183 generates a potential response curve in accordance with the data of the potential, correlates the timing signal with the potential response curve, and analyzes the characteristics of the potential response curve at each timing.

Here, specific operations of steps S205 and S206 are explained. Will know the low concentration (concentration C)_L) After the standard solution (L) in (2) is dispensed into the dilution tank 104, the diluent in the diluent bottle 109 is dispensed into the dilution tank 104 by using the diluent syringe pump 106, and the standard solution (L) of known low concentration is diluted at a predetermined ratio D1.

Next, the pipette syringe pump 107 is operated to draw the diluted standard solution (L) of known low concentration in the dilution tank 104 through the pipette nozzle N0 and introduce the solution into the flow paths of the ion selective electrodes 101A to 101C. Then, the reference electrode solution is introduced into the flow path of the reference electrode 102 from the reference electrode solution bottle 110.

At the liquid junction 120, the reference electrode liquid is brought into contact with a diluted known low-concentration standard liquid (L). Thereafter, the potentials between the ion-selective electrodes 101A to 101C and the reference electrode 102 are set to be the sameDifference (electromotive force EMF of known low concentration standard solution (L))_L) Measured by the potential measuring unit 171.

Measuring the EMF of a standard solution (L) of known low concentration_LMeanwhile, the standard liquid (L) remaining in the dilution tank 104 is sucked by the vacuum nozzle N3 and discarded in the waste liquid tank 111. Thereafter, the internal standard solution in the internal standard solution bottle 108 was redistributed to the dilution well 104 by using the internal standard solution syringe pump 105. Then, the internal standard solution in the dilution tank 104 was sucked by the pipette syringe pump 107, and the channels of the ion selective electrodes 101A to 101C were filled with the internal standard solution. Subsequently, the reference electrode solution is introduced from the reference electrode solution bottle 110 into the channel of the reference electrode 102.

Thereafter, similarly to the case of the known low concentration standard solution, the electromotive forces of the ion-selective electrodes 101A to 101C (measured electromotive forces EMF of the internal standard solution) in the state of being filled with the internal standard solution and the reference electrode solution are measured by the potential measuring unit 171_IS). During the measurement of the internal standard solution, the internal standard solution remaining in the dilution tank 104 is sucked by the vacuum nozzle N3 and discarded into the waste liquid tank 111. Thereafter, the known concentration (C) is determined_H) After the standard solution (H) in (c) is dispensed into the dilution tank 104, the diluent in the diluent bottle 109 is dispensed into the dilution tank 104 by using the diluent syringe pump 106, and the standard solution (H) having a known high concentration is diluted at a predetermined ratio D1.

The diluted standard solution (H) of known high concentration in the dilution tank 104 is sucked from the pipette nozzle N0 and introduced into the flow path of the ion selective electrodes 101A to 101C. Then, the reference electrode solution is introduced into the flow path of the reference electrode 102 from the reference electrode solution bottle 110.

At the liquid junction 120, the reference electrode liquid is brought into contact with a diluted known high-concentration standard liquid (H). Thereafter, the potential differences between the ion-selective electrodes 101A to 101C and the reference electrode 102 (the electromotive force EMF of the standard solution (H) having a known high concentration) are determined_H) Measured by the potential measuring unit 171.

Measuring the EMF of a standard solution (H) of known high concentration_HMeanwhile, the standard liquid (H) remaining in the dilution tank 104 is sucked by the vacuum nozzle N3 and discarded in the waste liquid tank 111. Thereafter, the internal standard solution bottle 1 is redistributed to the dilution tank 104 by using the internal standard solution injection pump 10508 internal standard solution. Then, the internal standard solution in the dilution tank 104 was sucked by the pipette syringe pump 107, and the channels of the ion selective electrodes 101A to 101C were filled with the internal standard solution. Subsequently, the reference electrode solution is introduced into the flow path of the reference electrode 102 from the reference electrode solution bottle 110. Thereafter, the electromotive forces of the ion-selective electrodes 101A to 101C are measured by the potential measuring unit 171 in the same manner as described above. The internal standard solution remaining in the dilution tank 104 is sucked by the vacuum nozzle N3 and discarded in the waste liquid tank 111.

The electromotive force EMF measured by the potential measuring unit 171 in accordance with the electromotive force EMF as described above_H、EMF_LThe concentration calculation unit 172 calculates the slope sensitivity SL of the calibration curve using the following equation (1).

[ equation 1 ]

SL＝(EMF_H－EMF_L)/(Log C_H－LogC_L) … … type (1)

The scaling is performed by the above operation. The slope sensitivity SL corresponds to 2.303 × (RT/zF) of the following formula (2) (nernst equation).

[ equation 2 ]

E0+2.303 × (RT/zF) × (f × C) … … formula (2)

E0: fixed potential determined by a measuring system

z: valence number of ion to be measured

F: faraday constant

R: gas constant

T: absolute temperature

f: coefficient of activity

C: ion concentration

The slope sensitivity SL can be obtained by calculation from the absolute temperature T and the valence z of the ion to be measured, but in order to further improve the analysis accuracy, in the first embodiment, the slope sensitivity SL specific to the electrode is obtained by performing the above-described calibration.

Further, the concentration Cis of the internal standard solution is determined based on the measured electromotive force EMF of the internal standard solution_ISThe following equations (3) and (4) are used.

[ equation 3 ]

Cis＝CL×10^a……Formula (3)

a＝(EMF_IS－EMF_L) /SL … … type (4)

Although the specific scaling procedure has been described above, the scaling procedure is not limited to the above procedure. In the above example, the measurement of the standard solution of known high concentration is carried out after the measurement of the standard solution of known low concentration, but the order may be reversed.

After the start-up of the apparatus is completed as shown in fig. 2(a), the sample is analyzed. In the analysis of the sample, the analysis of the sample and the analysis of the internal standard liquid are alternately and continuously performed.

The operation of continuous analysis of the sample and the internal standard solution will be described with reference to fig. 2 (b). After calibration, serum and urine were used as samples for analysis. Specifically, after the sample is dispensed into the dilution tank 104 by the sample dispensing nozzle (not shown), the diluent in the diluent bottle 109 is dispensed into the dilution tank 104 by the diluent syringe pump 106, and the sample is diluted at a set ratio D2 to generate a diluted sample solution. The diluted sample solution in the dilution tank 104 is sucked from the pipette nozzle N0 and introduced into the flow path of the ion-selective electrodes 101A to 101C. Further, a reference electrode solution is introduced from the reference electrode solution bottle 110 into the flow path of the reference electrode 102.

At the liquid junction 120, the reference electrode liquid is in contact with the diluted sample liquid. Thereafter, the respective potential differences between the ion-selective electrodes 101A to 101C and the reference electrode 102 (electromotive force EMF of the sample)_S) The diluted sample liquid can be analyzed by measurement by the potential measuring unit 171 (step S211).

During the measurement of the electromotive force of the diluted sample liquid, the diluted sample liquid remaining in the dilution tank 104 is sucked by the vacuum nozzle N3 and discarded into the waste liquid tank 111. Thereafter, the internal standard solution is redistributed from the internal standard solution bottle 108 to the dilution well 104 by using the syringe pump 105 for the internal standard solution. Then, the internal standard solution in the dilution tank 104 was sucked by the pipette syringe pump 107, and the channels of the ion selective electrodes 101A to 101C were filled with the internal standard solution. Subsequently, the reference electrode solution is introduced into the flow path of the reference electrode 102 from the reference electrode solution bottle 110. Thereafter, the electromotive force of each electrode is measured by the potential measuring unit 171, and the internal standard solution is analyzed (step S212).

Thus, when the diluted sample solution and the internal standard solution are analyzed, the sample concentration is calculated based on the result.

From the slope sensitivity SL and the concentration Cis of the internal standard solution, the concentration Cs of the sample is calculated using the following calculation formula (step S213).

[ equation 4 ]

Cs＝Cis×10^b… … type (5)

b＝(EMF_IS－EMF_S) /SL … … type (6)

The above calculation formula is a basic calculation formula. In the apparatus of the present embodiment, measurement of the internal standard solution with a fixed concentration is also performed before and after measurement of the diluted sample solution. Then, based on the measured value of the internal standard liquid, the measured value of the diluted sample liquid is corrected. Therefore, even when a change in the surface of the sensitive film of the ion-selective electrodes 101A to 101C or a gentle potential variation (potential drift phenomenon) due to a temperature change or the like occurs, accurate measurement can be realized.

In the various operations of steps S211 to S213 described above, timing signals for operating the various pumps 105 to 107, the electromagnetic valves V1 to V8, and other various driving units in the electrolyte concentration measuring apparatus 10 are output from the apparatus control unit 175. The timing signal is acquired by the timing signal acquisition unit 182. In steps S201 to S206, the potentials of the ion-selective electrodes 101A to 101C fluctuate, and the fluctuation is continuously monitored by the potential monitoring unit 181. The data of the monitored potential, that is, the data of the potential response curve is also sent to the timing signal acquisition unit 182, and is associated with the timing signal to perform data processing. The potential response curve analyzing unit 183 correlates the potential response curve with the timing signal, and acquires and analyzes the characteristic amount of the potential response curve at each timing.

Fig. 3 shows an example of a graph of a potential response curve obtained by the potential monitoring unit 181. In the figure, the horizontal axis represents time, the vertical axis represents potential, and the potential of the chloride ion electrode 101A, the potential of the sodium ion electrode 101C, and the potential of the potassium ion electrode 101B are represented in this order from the higher potential.

In the graph of fig. 3, the intervals a and a' are measurement intervals for measuring the diluted sample solution or the internal standard solution, and the interval B is a pause interval and an interval including an operation for returning to the measurement interval. Namely, the intervals a and a' are measurement intervals continuously executed with the pause interval B interposed therebetween. In fig. 3, only 2 measurement intervals a and a 'are shown, but such a measurement interval A, A' can be carried out a plurality of times.

When the measurement sections a and a' are continuously executed with the pause section B interposed therebetween, the internal standard solution and the diluted sample solution are alternately subjected to analysis. The detailed operation will be described later, but when the internal standard solution and the diluted sample solution are introduced into the ion-selective electrodes 101A to 101C, the flow path is first blocked by the pinch valve 103, but in this case, the ion-selective electrodes 101A to 101C show a high potential. Further, an air gap is introduced for diluting the sample solution and the internal standard solution, but in this case, the potentials of the ion-selective electrodes 101A to 101C also vary greatly.

In fig. 4, an enlarged view of a portion of the potential response curve of the measurement section a acquired by the potential monitoring unit 181 is shown superimposed on the timing signal acquired by the timing signal acquisition unit 182.

In the case of continuous analysis, the internal standard solution and the diluted sample solution are alternately introduced into the ion-selective electrodes 101A to 101C. The potential measuring unit 171 measures the potentials of the internal standard solution and the diluted sample solution at timings 401 and 402 when the potentials are relatively stable. At the timings 401 and 402, not only the data at 1 point but also the potentials can be measured a plurality of times at short time intervals and averaged.

If the potential can be obtained in the potential measuring unit 171, the concentration of the sample is calculated by the concentration calculating unit 172 using the data of the potential. The potential monitoring unit 181 can acquire a potential at intervals of 10ms (sampling rate), for example. The acquisition interval of the potential monitoring unit 181 may be changed, but in order to monitor the transient potential in the case of pressure fluctuation or the like, it is preferable to acquire the transient potential at an interval shorter than 100 ms.

In addition, since the data amount becomes large if the sampling rate is too high, it is preferable to acquire potential data at intervals of 0.01ms or more. The sampling rate of the potential monitoring unit 181 need not always be constant, and may be appropriately changed. For example, the sampling rate of the potential monitoring unit 181 may be set to a specific value and the other may be set to a different value only at the timing when the device element, the electrode, or the like concerned is operated. The sampling rate may be changed according to the type of the device element and the electrode concerned, or the operation state.

In addition, the deterioration pattern may be set to a timing at which the state change can be monitored, and the potential monitoring unit 181 may acquire only the potentials before and after the timing at which the timing signal acquisition unit 182 acquires the coincidence.

Here, with reference to fig. 4, an example of various operations occurring in the measurement section a will be described with reference to reference symbols in fig. 4. In the measurement of the internal standard solution, the pipette nozzle N0 descends (415) in the dilution tank 104 filled with the internal standard solution, and the tip of the pipette nozzle N0 enters the internal standard solution in the dilution tank 104. Thereafter, the pipette injection pump 107 is operated, and the internal standard solution is sucked (411) from the dilution tank 104 through the pipette nozzle N0 and introduced into the measurement flow path of the ion selective electrodes 101A to 101C.

Subsequently, the pipette nozzle N0 was raised to separate the tip thereof from the liquid surface of the internal standard solution (416), and thereafter, the air gap was introduced into the measurement channel by suction using the pipette syringe pump 107 (412). Thereafter, the pinch valve (417) is closed, the pipette syringe pump 107 is operated again, and the reference electrode solution is sucked from the reference electrode solution bottle 110 (413) and introduced into the channel of the reference electrode 102.

Thereafter, the pinch valve (418) is opened again, and after a certain time, the potential measuring unit 171 measures the potentials of the ion-selective electrodes 101A to 101C (401). Meanwhile, the electromagnetic valve V8 connected to the measurement flow path and the like are closed, and the liquid in the pipette syringe pump 107 is discharged (414).

In the case of the sample measurement in fig. 4, the operation is almost the same as that in the case of the internal standard solution measurement. In the dilution tank 104, the sample is diluted with a diluent supplied from a diluent tank 109. Thereafter, in the dilution tank 104 filled with the diluted sample solution, the pipette nozzle N0 is lowered (425), and the tip of the pipette nozzle N0 enters the diluted sample solution in the dilution tank 104. Thereafter, the pipette syringe pump 107 is operated, the diluted sample solution is sucked (421) from the dilution tank 104 through the pipette nozzle N0, and the diluted sample solution is introduced into the measurement flow path of the ion-selective electrodes 101A to 101C.

Subsequently, the pipette nozzle N0 is raised to separate the tip from the liquid surface of the diluted sample solution (426), the pipette syringe pump 107 sucks the sample solution to introduce an air gap into the measurement channel (422), the pinch valve (427) is closed, the pipette syringe pump 107 is operated again to suck the reference electrode solution from the reference electrode solution bottle 110 (423), and the reference electrode solution is introduced into the channel of the reference electrode 102.

Thereafter, the pinch valve 428 is opened again, and after a certain time, the potential measuring unit 171 measures the potentials of the ion selective electrodes 101A to 101C (402). Meanwhile, the electromagnetic valve V8 connected to the measurement flow path and the like are closed, and the liquid in the pipette syringe pump 107 is discharged (424).

Timing signals (411 to 428) for instructing the start and end of driving of the various members are acquired from the device control unit 175 by the timing signal acquisition unit 182. The acquired timing signal is sent to the potential response curve analysis unit 183. This series of actions is performed almost simultaneously. In addition to the timing signals specifically shown in fig. 4, timing signals for instructing the opening and closing of the solenoid valves V1 to V8, timing signals for instructing the distribution operation in the dilution tank 104, timing signals for instructing the vacuum suction operation, and the like are also output from the apparatus control unit 175 and acquired by the timing signal acquisition unit 182. Further, the potential monitoring unit 181 may be configured as follows: the potential is monitored not only during the continuous analysis of the measurement intervals a, a' in fig. 3, but also during the pause interval B, and at the start-up or timing of the device.

As shown in fig. 4, the timing signals 411 to 428 and the potential response curve obtained by the potential monitoring unit 181 are recorded in time series, and various kinds of information can be read. For example, when the pipette nozzle N0 is lowered or raised, it is estimated that a potential change due to contact with the liquid in the dilution tank 104, vibration of the liquid in the flow path, or the like appears in the potential response curve. In addition, the suction and discharge operations of the pipette syringe pump 107 also cause vibrations to be transmitted to the various electrodes and other constituent elements, thereby causing a potential change in the potential response curve.

As described above, in the apparatus according to the first embodiment, since the suction, discharge, channel switching operation, and the like of the liquid are frequently performed at short time intervals, not only the ion concentration and temperature in the liquid but also information such as pressure fluctuation, vibration, electrical noise, and the like can be obtained from the transient potential acquired by the potential monitoring unit 181.

When the diluted sample solution and the internal standard solution were aspirated by the pipette syringe pump 107, a transient response curve, which is considered to be caused by a change in the ion concentration of the solution, was observed. When a channel, which is a channel for an ion solution (diluted sample solution or internal standard solution), is blocked by the pinch valve 103, the ion solution is cut off in the channel, and a rapid increase in potential is observed.

In this way, in each timing signal, the states (degree of deterioration, failure, others) of the element and the electrode to be operated at this time can be clarified from the analysis result of the potential response curve. For example, based on a potential change appearing in a potential response curve when a timing signal indicating the closing of the pinch valve 103 is output, it is possible to judge the degree of deterioration of the tube inside the pinch valve 103, the presence or absence of a failure of the pinch valve 103 itself, and the like.

At the timing when the ion solution is sucked and discharged by the pipette syringe pump 107, the movement of the ion solution, the movement of air bubbles, pressure fluctuation, electrical noise, and the like appear as changes in potential. Further, a change in the degree of leakage of the solenoid valves, deterioration of the sealing portions of the syringe pumps 105 to 107, a change in the physical properties of the inductive films of the ion-selective electrodes 101A to 101C, and the like can also be detected by correlation with the timing signals. Such information on the deterioration and fluctuation is hard to appear in the measured potentials of the ion-selective electrodes 101A to 101C, and is hard to detect even if another sensor is added. However, according to the first embodiment, since the timing signal is correlated with the potential response curve and analyzed by the potential response curve analyzing unit 183, the degree of deterioration can be easily determined from the potential response curve.

Further, together with the predetermined timing signals, the state of contamination of the surfaces of the sensor membranes of the ion selective electrodes 101A to 101C can be determined from the potential response curves before and after the internal standard solution, the ion solution having a known concentration different from the internal standard solution, and the ion solution containing interfering ions are attracted to the channels of the ion selective electrodes 101A to 101C. Further, if a measurement result is obtained that the surfaces of the sensing films of the ion-selective electrodes 101A to 101C are suspected to be contaminated, the electrode flow paths including the surfaces of the sensing films can be cleaned with a cleaning liquid at the time of maintenance, thereby enabling the measurement flow paths to be refreshed.

When a specific change is detected in the potential of any one of the ion-selective electrodes 101A to 101C, it can be determined that there is a high possibility that a sign of deterioration or failure occurs in any one of the ion-selective electrodes 101A to 101C. On the other hand, when the potentials of all the ion-selective electrodes 101A to 101C are changed similarly and specifically, it can be determined that there is a high possibility that an abnormality is generated in the reference electrode 102 or an element in another device, not the ion-selective electrodes 101A to 101C.

The potential response curve analyzing unit 183 is provided with a data storage unit 184 for storing library data on the characteristic amount of the potential response curve. The library data is a set of data relating to various characteristic quantities of a standard potential response curve that can be obtained when the apparatus is in a normal state. The potential response curve analyzing unit 183 compares the characteristic amount of the library data with the characteristic amount of the potential response curve obtained as a result of the measurement at the timing at which the signal is output at each timing. This makes it possible to determine the state of deterioration of various electrodes and device elements, contamination of the surfaces of the inductive films of the ion-selective electrodes 101A to 101C, and the like.

The library data may be standard data obtained as a result of the simulation, or a potential response curve obtained immediately after the user sets the device 10 and operates it first may be used as the library data. The library data may also be updated as appropriate based on the results of measurements performed thereafter. Depending on the installation location of the device 10, vibration, electrical noise, and the like may vary depending on the environment and the like. Therefore, by actually operating the apparatus 10 to obtain the library data, it is expected that the accuracy of the abnormality indication is improved. Further, the library data may be uploaded and downloaded via a network or the like.

As described above, in the electrolyte concentration measuring apparatus 10 according to the first embodiment, the timing signals indicating the timings of the various operations and the potential response curve obtained by calculating the potential of the ion selective electrode are acquired by correlating them with each other and analyzed, whereby the sign of the abnormality can be detected, and the maintenance can be planned before the abnormality occurs in the measured potential by prediction, and then the maintenance can be performed in accordance with the plan. For example, the potential response curve analysis unit 183 can determine a sign of a physical change of the ion selective electrode 101 and deterioration of various mechanism units based on waveforms of potential response curves of the various mechanism units during operation and immediately after operation, which are caused by timing signals. Further, the potential response curve analysis unit 183 can determine contamination of the surface of the ion sensitive film of the ion selective electrode 101 based on the waveform of the potential response curve at the time of stopping the operation of the various mechanism units related to the movement of the liquid in the liquid flow path due to the timing signal.

As a method for analyzing the potential response curve, a general method used for analyzing time series data may be used, and machine learning, deep learning, and the like may be used. In addition, the behavior of elements in other devices and the like that are affected by the operation of various elements and electrodes following the timing signals can be predicted or simulated using device configurations, physical equations, and the like, and the results can be used for the analysis of the potential response curve.

Referring to fig. 5, a method of monitoring the potential of the sodium ion electrode 101C and determining a sign of an abnormality will be specifically described. Fig. 5 shows a potential response curve (NA1) obtained by measuring a predetermined sample solution using the sodium ion electrode 101Ce whose storage life has elapsed, and a potential response curve (NA2) obtained by measuring the same sample solution using the sodium ion electrode 101Cn which is relatively new and whose storage life has not elapsed. In fig. 5, timing signals indicating the timing of the suction and discharge operations of the pipette syringe pump 107, the timing of the ascent and descent of the pipette nozzle N0, and the timing of the opening and closing operations of the pinch valve 103 are also shown.

In the graph of fig. 5, the slope sensitivity of the old sodium ion electrode 101Ce was 59.2 mV/digit, and the slope sensitivity of the new sodium ion electrode 101Cn was 60.0 mV/digit, both of which were within the allowable range. In addition, the measurement accuracy within the allowable range can be obtained from either the potential response curve NA1 obtained from the old sodium ion electrode 101Ce or the potential response curve NA2 obtained from the new sodium ion electrode 101 Cn.

However, as shown in fig. 5, immediately after the pipette syringe pump 107 starts sucking the sample liquid after the pipette nozzle N0 descends, the potential of the potential response curve NA1 changes rapidly compared to the potential response curve NA2, and thereafter, the potential gradually returns. In this case, although not shown in fig. 5, no drastic change was observed in the potential response curves of the chloride ion electrode 101A and the potassium ion electrode 101B.

When the above-described information is acquired, it can be determined that the deterioration of the sodium ion electrode 101Ce has progressed. The result of this determination is output by the output unit 174. The output unit 174 issues an alarm to the operator, and replaces the sodium ion electrode 101Ce when the apparatus is maintained next time. In this way, the measurement accuracy is within the allowable range, but the presence of the sign of abnormality can be determined by analyzing the shape of the potential response curve. By detecting the sign of an abnormality in this way, the operator can correctly make a maintenance plan and carry out maintenance in accordance with the plan.

Referring to fig. 6, a method of monitoring the potential of the chloride ion electrode 101A and determining a sign of an abnormality will be specifically described. Fig. 6 shows a potential response curve (Cl1) obtained by measuring a predetermined sample solution with the chloride ion electrode 101Ae having a first state as the surface state of the ion-sensitive membrane, and a potential response curve (Cl2) obtained by measuring the same sample solution with the chloride ion electrode 101An having a second state different from the first state. Fig. 6 also shows timing signals indicating the timing of the suction and discharge operations of the pipette syringe pump 107, the timing of the rise and fall of the pipette nozzle N0, and the timing of the opening and closing operations of the pinch valve 103. Fig. 6 is a view showing a case where an aqueous solution containing interfering ions is measured as a measurement target (sample).

As shown in fig. 6, immediately after the pipette nozzle N0 descends and the pipette syringe pump 107 starts sucking the sample, the chloride electrode 101Ae and the chloride electrode 101An are both rapidly raised in potential. This is because the liquid in the flow paths of the electrodes 101Ae and 101An is replaced with the sample from the internal standard liquid, and the liquid composition is changed. In the latter half of the sample suction operation, the curve Cl1 has an upward convex peak, while the curve Cl2 rises gently and no upward convex peak appears. On the other hand, the measured potential at the timing 402 when the concentration of the sample was calculated was almost the same as the curves Cl1 and Cl 2. In this way, the characteristics (presence or absence of a peak having a protrusion, its amplitude, and width) of the waveform in the potential response curve at the timing when the timing signal is output are calculated as characteristic amounts, and compared with the reference values, it is possible to determine the sign of an abnormality.

The reason why the difference occurs in the waveforms of the potential response curves Cl1 and Cl2 between the time of sample suction and the time after suction is considered to be due to the difference in the state of the ion-sensitive membrane surface of the chloride ion electrodes 101Ae and 101An or the difference in the ion balance in the ion-sensitive membrane.

By correlating the timing signal with the potential response curve in this manner, it is possible to detect a phenomenon that is difficult to detect when only the measurement potential is measured.

[ second embodiment ]

Next, an electrolyte concentration measurement device 10 according to a first embodiment of a second embodiment will be described with reference to fig. 7 to 8. Fig. 7 is a schematic diagram showing an example of the flow-type electrolyte concentration measuring apparatus 10 according to the second embodiment. The same components as those in the first embodiment (fig. 1) are denoted by the same reference numerals, and redundant description thereof will be omitted below.

The electrolyte concentration measuring apparatus 10 according to the second embodiment includes various sensors for detecting behavior in the apparatus 10, and detection signals of these sensors are acquired by the timing signal acquiring unit 182, and the potential response curve analyzing unit 183 analyzes the potential response curve based on the correlation between the timing signal, the detection signal of the sensor, and the potential response curve, and determines a sign of abnormality of the apparatus based on the result. Here, an air bubble sensor 121 for detecting air bubbles in the pipe and a pressure sensor 122 for detecting the pressure in the flow path arranged in the flow path connecting the pipette syringe pump 107 and the liquid junction 120 are shown as examples of the sensors. The type of the sensor is not limited to this, and for example, a liquid level sensor for detecting a change in the liquid level in the dilution tank 104 or the like, a vibration sensor for detecting vibration of an electrode or other various elements, or the like may be included in the apparatus 10. The bubble sensor 121 generates a pulse signal when a bubble having a size equal to or larger than a predetermined size passes through a predetermined position. The pressure sensor 122 generates a pulse signal when the pressure at the measurement position reaches a predetermined value. Not limited to this, the pressure value may be continuously output at any time.

The operation of the second embodiment will be described with reference to fig. 8. In fig. 8, an enlarged view of a portion of the potential response curve of the measurement section a acquired by the potential monitoring unit 181, and the timing signal and the sensor detection signal acquired by the timing signal acquisition unit 182 are displayed in a superimposed manner. In the first embodiment, the timing signal output from the apparatus control unit 175 is acquired by the timing signal acquisition unit 182 and correlated with the potential response curve, but in the second embodiment, the sensor detection signals of the sensors 121 and 122 are also correlated with the potential response curve in addition to the timing signal. The timing at which the predetermined sensor detection signal is output is correlated with the timing at which the timing signal is output from the device control unit 175. Therefore, by acquiring the sensor detection signal by the timing signal acquisition unit 182, the behavior of the apparatus 10 can be accurately correlated with the potential response curve, and the sign of the abnormality can be more accurately determined.

The present invention is not limited to the above embodiments, and includes various modifications. For example, the above embodiments have been described in detail to explain the present invention in an easily understandable manner, but the embodiments are not limited to having all the configurations described. In addition, a part of the configuration of one embodiment may be replaced with the configuration of another embodiment, or the configuration of another embodiment may be added to the configuration of one embodiment. Further, a part of the configuration of each embodiment may be added, deleted, or replaced with another configuration.

Description of the symbols

101 … ion selective electrodes, 101a … chloride ion electrode, 101B … potassium ion electrode, 101C … sodium ion electrode, 102 … reference electrode, 03 … pinch valve, 104 … dilution tank, injection pump for 105 … internal standard solution, injection pump for 106 … dilution solution, injection pump for 107 … pipette, internal standard solution bottle 108 …, diluent solution bottle 109 …, reference electrode solution bottle 110 …, waste solution tank 111 …, vacuum pump 112 …, liquid junction part 120 …, bubble sensor 121 …, pressure sensor 122 …, electromagnetic valves V1 to V8 …, potential measuring part 171 …, concentration calculating part 172 …, output part 174 …, device control part 175 …, input part 176 …, potential monitoring part 181 …, timing signal acquiring part 182 …, 183 … potential response curve analyzing part 183, and data storing part 184 ….