Automated analyzer

Abstract

In order to provide an automated analyzer which is provided with an electrolyte analysis unit that is capable of automatically cleaning a dilution tank with a high cleaning effect, the present invention is configured as follows.　This automated analyzer comprises: a dilution tank for diluting a sample; a cleaning liquid container for storing a cleaning liquid for cleaning the dilution tank; a flow passage for connecting a discharge nozzle for discharging the cleaning liquid to the dilution tank and the cleaning liquid container; a heating unit which is in direct or indirect contact with the flow passage and heats the cleaning liquid flowing through the flow passage; and an electrolyte measurement unit which has an ion selection electrode for measuring the ion concentration in the sample that is diluted in the dilution tank. The automated analyzer comprises a control unit for controlling the heating unit so that the temperature of the cleaning liquid becomes a predetermined temperature when the cleaning liquid stored in the cleaning liquid container is discharged to the dilution tank through the flow passage and the discharge nozzle when the cleaning liquid is supplied to the dilution tank.

Description

automatic analyzer

[0001] The present invention relates to an automatic analyzer.

[0002] Electrolyte analyzers are known for measuring the concentration of specific ions in biological samples such as blood by using ion-selective electrodes to measure the magnitude of the electromotive force generated by the ion concentration. In a typical electrolyte analyzer, the sample is aspirated by a sample probe and discharged into a dilution tank. The dilution solution is then dispensed into the dilution tank from a dilution solution nozzle to dilute the sample. The diluted sample is then transferred to the ion-selective electrode by a sipper nozzle, where it is measured. The diluted sample remaining in the dilution tank is aspirated and discarded by a vacuum nozzle, after which it is cleaned. The dilution tank, sample probe, sipper nozzle, and vacuum nozzle are repeatedly used, resulting in the accumulation of dirt. To remove the dirt, users manually wipe them down with alcohol-soaked cotton swabs or gauze.

[0003] However, the sample probe has a very thin tip with a diameter of about 1 mm, and it is possible that the probe will be bent when wiping and cleaning, which may result in insufficient wiping. Furthermore, the dilution tank is equipped with a diluent nozzle for diluting the specimen, a sipper nozzle for aspirating the specimen, and a vacuum nozzle for discarding the liquid remaining in the dilution tank. Therefore, cleaning requires the laborious task of removing each of these nozzles from the dilution tank, and these nozzles may be bent in the same way as the sample probe.

[0004] Patent Document 1 describes a technology for automatically cleaning a dilution tank without human intervention, in which detergent is aspirated from a cleaning container placed on a cleaning rack using a sample nozzle and dispensed into the dilution tank, and after a certain period of time, the detergent is aspirated using a waste liquid nozzle and discarded.

[0005] Japanese Patent Application Laid-Open No. 2018-169166

[0006] The cleaning solution used in the technology described in Patent Document 1 is supplied to the dilution tank at room temperature, so even if the cleaning solution is left in the cleaning tank for rinsing, depending on the level of dirt, there is a possibility that some dirt may remain that cannot be removed.

[0007] The present invention has been made in view of the above-mentioned problems, and has as its object to provide an automatic analyzer equipped with an electrolyte analyzing unit that can automatically clean a dilution tank with a high cleaning effect.

[0008] The present invention achieves the above object in the following manner: An automatic analyzer includes a dilution tank for diluting a sample, a cleaning liquid container for containing a cleaning liquid for cleaning the dilution tank, a flow path connecting the cleaning liquid container to a discharge nozzle for discharging the cleaning liquid into the dilution tank, a heating unit that is in direct or indirect contact with the flow path and heats the cleaning liquid flowing through the flow path, and an electrolyte measuring unit having an ion selective electrode that measures the ion concentration in the sample diluted in the dilution tank, and includes a control unit that, when the cleaning liquid is supplied to the dilution tank, controls the heating unit so that the temperature of the cleaning liquid is maintained at a predetermined temperature when the cleaning liquid contained in the cleaning liquid container is discharged into the dilution tank through the flow path and the discharge nozzle.

[0009] According to the present invention, an automatic analyzer having an electrolyte analyzing unit capable of automatically cleaning a dilution tank with high cleaning efficiency can be provided. Other objects, configurations, advantages, etc. of the present invention will become clear from the description of the following embodiments.

[0010] Overall schematic diagram of the electrolyte analysis unit. Schematic diagram of the temperature control unit with a discharge nozzle that warms the cleaning solution. Time chart of the cleaning process, which simultaneously cleans the dilution tank, sample probe, sipper nozzle, and vacuum nozzle. Time chart of the rinsing process, which simultaneously rinses the dilution tank, sample probe, sipper nozzle, and vacuum nozzle. Display screen for setting the cleaning target, cleaning cycle, and cleaning timing. Flowchart for automatic re-cleaning during ISE check operation.

[0011] Hereinafter, an embodiment of the present invention will be described with reference to the drawings.

[0012] FIG. 1 is a schematic diagram of an overall electrolyte analyzer according to a first embodiment of the present invention. The electrolyte analyzer of this embodiment is configured as an automatic analyzer or a part thereof. Examples of such automatic analyzers include an automatic biochemical analyzer and an automatic immunological analyzer. Alternatively, the automatic analyzer may be a mass spectrometer used in clinical testing, a coagulation analyzer that measures blood clotting time, or the like. Alternatively, the automatic analyzer may be a combined system of a mass spectrometer or coagulation analyzer and an automatic biochemical analyzer or an automatic immunological analyzer, or may be an automatic analysis system that utilizes these. Below, an embodiment will be described in which the electrolyte analyzer is configured as a standalone automatic analyzer (in this case, it will also be referred to as an "electrolyte analyzer" rather than an "electrolyte analyzer").

[0013] The electrolyte analysis unit shown in FIG. 1 is a flow-type electrolyte analyzer that uses an ion selective electrode (hereinafter, referred to as an ISE electrode). FIG. 1 shows five main mechanisms of the flow-type electrolyte analyzer: a sample dispensing unit, an ISE electrode unit, a reagent unit, a liquid delivery unit, and a liquid waste mechanism. It also shows a control device 29 (control unit) that controls these mechanisms and calculates and displays the electrolyte concentration from the measurement results.

[0014] The sample dispensing unit includes a sample probe 14 and a sample container 15. The "sample container" is also referred to as a "specimen container." The sample probe 14 dispenses a sample (hereinafter also referred to as a "specimen" or "analyte") held in the sample container 15 and draws it into the automated analyzer. Here, the "analyte" is a general term for an object to be analyzed collected from a patient's living body, such as blood or urine. The specimen may also be one that has been subjected to pretreatment such as centrifugation on the object to be analyzed.

[0015] The ISE electrode section includes a dilution tank 11, a shipper nozzle 13, a diluent nozzle 24, an internal standard nozzle 25, an ion selective electrode 1, a reference electrode 2, a pinch valve 23, a voltmeter 27, an amplifier 28, and a temperature control section 40. The "ion selective electrode" is sometimes abbreviated as "ISE electrode." The sample aspirated by the sample dispensing section is discharged into the dilution tank 11, where it is diluted and stirred with the diluent discharged from the diluent nozzle 24 into the dilution tank 11. The shipper nozzle 13 is connected to the ion selective electrode 1 by a flow path, and the diluted sample solution aspirated from the dilution tank 11 is delivered to the ion selective electrode 1 by this flow path.

[0016] Meanwhile, the reference electrode solution contained in the reference electrode solution bottle 5 is sent to the reference electrode 2 by operating the sipper syringe 10 with the pinch valve 23 closed. When the pinch valve 23 is then opened, the diluted sample solution sent to the ISE electrode flow path comes into contact with the reference electrode solution sent to the reference electrode flow path, establishing electrical continuity between the ion selective electrode 1 and the reference electrode 2. The ISE electrode section measures the concentration of a specific electrolyte contained in the sample based on the potential difference (liquid junction potential) between the ion selective electrode 1 and the reference electrode 2.

[0017] As a specific example, the ion selective electrode 1 is configured to detect a specific ion (e.g., sodium ion (Na ＋ ), potassium ions (K ＋ ), chloride ion (Cl － An ion-sensitive membrane having a property that its electromotive force changes depending on the concentration of ions (e.g., ions in the sample solution, etc.) is attached to the dilution tank 11. This causes the ion-selective electrode 1 to output an electromotive force corresponding to the concentration of each ion in the sample solution, and a voltmeter 27 and an amplifier 28 acquire the electromotive force between the ion-selective electrode 1 and the reference electrode 2. The control device 29 calculates and outputs the ion concentration in the specimen for each ion from the acquired electromotive force (for example, by displaying it on a display device (not shown) provided in the control device 29). The sample solution remaining in the dilution tank 11 is discharged by a waste liquid mechanism (to be described later).

[0018] The reagent section includes a suction nozzle 6 that aspirates reagent from a reagent container and supplies the reagent required for measurement. The reagent section may also include a degassing mechanism 7 and a filter 16 for removing gases such as air contained in the reagent. When performing electrolyte measurements, three types of liquid are used as reagents: an internal standard solution, a diluent, and a reference electrode solution. An internal standard solution bottle 3, a diluent solution bottle 4 that contains the diluent, and a reference electrode solution bottle 5 that contains the reference electrode solution are set in the reagent section as reagent containers that contain the internal standard solution. Figure 1 shows this state. When cleaning the device, a cleaning solution bottle that contains cleaning solution may also be set in the reagent section.

[0019] The internal standard bottle 3 and diluent bottle 4 are connected to an internal standard nozzle 25 and a diluent nozzle 24 via a flow path via a filter 16, respectively, and each nozzle is installed with its tip inserted into the dilution tank 11. The reference electrode solution bottle 5 is connected to the reference electrode 2 via a flow path via a filter 16. A degassing mechanism 7 is connected to the flow path between the diluent bottle 4 and the dilution tank 11, and to the flow path between the reference electrode solution bottle 5 and the reference electrode 2, respectively, and degassed reagent is supplied to the dilution tank 11 and the reference electrode 2.

[0020] The liquid delivery unit includes an internal standard syringe 8, a diluent syringe 9, a shipper syringe 10, and solenoid valves 17, 18, 19, 20, 21, 22, and 30, and is responsible for operations such as liquid delivery within each mechanism or between each mechanism. The liquid delivery unit may also include a preheater 12 for heating the liquid to be delivered. For example, the internal standard and diluent are delivered to the dilution tank 11 by the operation of the internal standard syringe 8 and the diluent syringe 9, respectively, and the corresponding solenoid valves provided in the flow path. The preheater 12 controls the temperatures of the internal standard and diluent reaching the ion selective electrode 1 within a certain range of approximately 37°C, which is the same as the reaction temperature in biochemical analysis, thereby suppressing the effect of temperature on the ion selective electrode 1.

[0021] The waste liquid mechanism includes a vacuum nozzle 26, a waste liquid nozzle 36, a vacuum bottle 34, a waste liquid receiver 35, a vacuum pump 33, and solenoid valves 31 and 32, and discharges the sample solution remaining in the dilution tank 11 and the reaction liquid (waste liquid) remaining in the flow path of the ISE electrode section. The above is the general configuration of a flow-type electrolyte analyzer.

[0022] As an example of the operation of the flow-type electrolyte analyzer shown in FIG. 1 , the operation of measuring electrolyte concentration will be described. The measurement operation is controlled by the control device 29. First, the sample aspirated from the sample container 15 by the sample probe 14 of the sample dispensing unit is dispensed into the dilution tank 11 of the ISE electrode unit. Then, the dilution liquid is dispensed from the dilution liquid bottle 4 through the dilution liquid nozzle 24 into the dilution tank 11 by the operation of the liquid delivery unit (particularly, the dilution liquid syringe 9). The sample is diluted with the dilution liquid in the dilution tank 11. As mentioned above, to prevent the generation of bubbles due to temperature and pressure changes in the dilution liquid in the flow path, a degassing process may be performed using the degassing mechanism 7 installed midway along the dilution liquid flow path. The diluted sample solution is then aspirated into the ion-selective electrode 1 by the operation of the liquid delivery unit (particularly, the sipper syringe 10 and the solenoid valve 22).

[0023] Meanwhile, the reference electrode solution is sent from the reference electrode solution bottle 5 to the reference electrode 2 by the operation of the solution sending section (particularly the pinch valve 23 and the sipper syringe 10). The reference electrode solution is, for example, an aqueous potassium chloride (KCl) solution of a predetermined concentration. After the reference electrode solution has been sent, the pinch valve 23 is opened to bring the sample solution and the reference electrode solution into contact, thereby establishing electrical continuity between the ion selective electrode 1 and the reference electrode 2. The ISE electrode potential (liquid junction potential) relative to the reference electrode potential is measured using a voltmeter 27 and an amplifier 28.

[0024] To suppress the effects of concentration fluctuations while the sample solution is being delivered, it is desirable to have a high electrolyte concentration in the reference electrode solution. However, a concentration close to saturation may cause crystallization and block the flow path. Taking all of these factors into consideration, it is generally desirable for the electrolyte concentration of the reference electrode solution to be between 0.5 mmol / L (millimoles / liter) and 3.0 mmol / L (millimoles / liter).

[0025] In addition, before or after the measurement using the sample solution, the internal standard solution in the internal standard solution bottle 3 set in the reagent section is discharged into the dilution tank 11 using the internal standard solution syringe 8, and the electrolyte concentration of the internal standard solution is measured in the same manner as in the measurement using the sample solution.

[0026] The ISE electrode potential measured for the sample solution is used in the control device 29 to perform calculations to calculate the electrolyte concentration in the sample solution. At this time, calibration based on the ISE electrode potential measured for the internal standard solution can be performed to measure the electrolyte concentration more accurately. The specific calculation content of the calibration process can be designed as appropriate by those skilled in the art based on well-known techniques.

[0027] The control device 29 can be configured as a computer including a calculation means such as a CPU (Central Processing Unit), a storage means such as a RAM (Random Access Memory), and an input / output means such as an I / O port. The storage means and the input / output means are configured to be able to exchange data with the calculation means via an internal bus or the like. The input / output means is connected to each of the above-mentioned mechanisms of the electrolyte analyzer, and the control device 29 controls the operation of each mechanism via the input / output means.

[0028] The storage means may store a program that defines the operation of the electrolyte analyzer, and the control device 29 may control the operation of the electrolyte analyzer by executing this program. This program is read from the storage means and executed by the calculation means. In addition, an input / output device may be connected to the control device 29, and the electrolyte analyzer may receive input from a user and display measurement results via this input / output device.

[0029] Next, the temperature control unit with a discharge nozzle for heating the cleaning solution in the flow-type electrolyte analyzer of this embodiment will be described with reference to FIG. 2. The temperature control unit (also referred to as the "heating unit") of this embodiment is configured as the temperature control unit 40 shown in FIG. 1. The temperature control unit is configured to heat the cleaning solution by covering the outer periphery of the temperature control unit with a rubber heater 50. The rubber heater 50 is in direct contact with the cleaning solution flow path that passes through the temperature control unit, or the flow path is heated indirectly via a highly thermally conductive material, thereby heating the cleaning solution flowing through the flow path. The amount of detergent to be heated can be designed by changing the diameter of the third flow path 51 and the length of the temperature control unit, depending on whether the dilution layer is to be washed once or repeatedly.

[0030] In this case, the temperature at which the detergent is heated is preferably 40°C to 70°C. The higher the heating temperature, the better the cleaning effect can be expected; however, if the temperature exceeds 70°C, the temperature of the detergent may partially approach the boiling point, causing bumping, depending on the structure of the heating mechanism and the accuracy of the heating control. Furthermore, since a significant improvement in cleaning effect cannot be expected at temperatures below 40°C, the range in this embodiment is 40°C to 70°C. If the structure of the heating mechanism and the accuracy of the heating control are such that bumping can be suppressed, it is also possible to heat the detergent at a temperature higher than 70°C. A heat insulating material 52 may be wrapped around the rubber heater to prevent the heated cleaning liquid from cooling down.

[0031] The temperature control unit is configured to be able to directly discharge the heated cleaning liquid into the dilution tank. While it is possible to discharge the cleaning liquid heated by the temperature control unit into the dilution tank from a nozzle separately arranged near the dilution tank, it is desirable to have a discharge nozzle 53 that can discharge the cleaning liquid directly from the temperature control unit, since the temperature of the heated cleaning liquid may drop while passing through the flow path from the temperature control unit to the nozzle. The cleaning liquid is automatically supplied to the temperature control unit from a cleaning liquid bottle 55 containing the cleaning liquid via a first flow path 54. The cleaning liquid is, for example, an alkaline detergent.

[0032] The device also includes a second flow path 56 for supplying system water. System water is automatically supplied, just like the cleaning liquid. While syringes 43 and 46 are used to supply the cleaning liquid and system water in FIG. 2 , a peristaltic pump or other means other than syringes can be used as the supply means as long as the required amount can be supplied. It is preferable that the cleaning liquid (first flow path 54) be supplied from below the temperature control unit, and the system water (second flow path 56) be supplied from above the temperature control unit (i.e., midway along the flow path connecting the temperature control unit heated by the rubber heater 50 and the discharge nozzle 53). By arranging the flow paths for the cleaning liquid and system water in separate locations, the operation of replacing the cleaning liquid in the third flow path 51 with system water can be eliminated, thereby reducing the consumption of cleaning liquid.

[0033] Furthermore, if two flow paths are provided so that both are supplied from the lower side of the temperature control unit, the temperature control unit itself would become larger and two discharge nozzles would have to be provided, which would lead to increased costs, and this is not preferable. Therefore, by arranging the first flow path 54 and the second flow path 56 in different positions and using a three-way electromagnetic valve 57 to switch between the third flow path 51 and the second flow path 56, it becomes possible to switch the type of liquid to be discharged.

[0034] Since alkaline detergents may precipitate crystals over time, running system water to prevent precipitation of crystals can eliminate the need for cleaning and maintenance of the temperature control unit's discharge nozzle 53. In addition, although the present embodiment describes a configuration in which the rubber heater 50 is used to control the temperature of the third flow path 51, any heater other than a rubber heater can be used as heating means as long as it is configured to cover the third flow path 51.

[0035] As described above, the dilution tank 11 is accessible to the sample probe 14 for aspirating a sample from the sample container 15 and discharging it into the dilution tank 11, the sipper nozzle 13 for aspirating the sample that has been diluted with diluent discharged from the diluent nozzle 24 after being discharged into the dilution tank 11, and the vacuum nozzle 26 for discarding the diluted sample remaining in the dilution tank. Therefore, by discharging a cleaning solution warmed by a temperature control unit into the dilution tank 11 and immersing each nozzle in the discharged cleaning solution, it is possible to simultaneously immerse and clean the dilution tank 11, the sample probe 14, the sipper nozzle 13, and the vacuum nozzle 26.

[0036] It is desirable to perform the soaking cleaning while the device is in standby mode (when there are no measurement requests and the device is idling). The time the device is in standby mode depends on the facility where the device is operated and cannot be generalized, but it is thought to be in most cases between a few minutes and a few tens of minutes, so the soaking cleaning time is also expected to be between a few minutes and a few tens of minutes. Within that time, the heated cleaning solution will not cool down to room temperature, so the effects of soaking cleaning with heated cleaning solution can be fully expected.

[0037] Generally, the soaking cleaning is performed on the dilution tank 11 and mainly on the outside of each nozzle. Furthermore, during the soaking cleaning, the inside of each nozzle can also be cleaned by sucking the warmed cleaning liquid from each nozzle.

[0038] FIG. 3 shows a time chart of the cleaning process for simultaneously cleaning the dilution tank 11, sample probe 14, shipper nozzle 13, and vacuum nozzle 26. In S101, cleaning solution supplied from the first flow path 54 is heated in the third flow path 51 and then discharged into the dilution tank 11. When discharging the cleaning solution into the dilution tank 11, the cleaning solution to be discharged from the first flow path 54 is supplied to the third flow path 51 in an amount to be discharged into the dilution tank 11, thereby pushing out and discharging the cleaning solution heated in the third flow path 51. As described above, a fixed amount of cleaning solution can be discharged into the dilution tank 11 by using, for example, a syringe 43. The first flow path 54 for supplying the cleaning solution is connected to a cleaning solution bottle 55, and the first flow path 54 is equipped with solenoid valves 41 and 42 and a syringe 43. First, the solenoid valve 41 is opened, and the syringe 43 is operated to draw the required amount of cleaning solution from the cleaning solution bottle 55. Thereafter, the solenoid valve 41 is closed, the solenoid valve 42 is opened, and the syringe 43 is operated, thereby enabling a fixed amount of the cleaning liquid to be discharged into the dilution tank 11 .

[0039] The amount of heated cleaning liquid (hereinafter referred to as heated cleaning liquid) discharged here is the amount required to wash the outside and inside of the dilution tank 11 and sample probe 14, the outside and inside of the shipper nozzle 13, and the outside of the vacuum nozzle 26. When washing all of these simultaneously, the amount of heated cleaning liquid discharged into the dilution tank 11 is, for example, as follows:

[0040] (Reagent discharge volume and sample volume dispensed into dilution tank: 550 μL) + (Maximum suction volume of sample probe: 25 μL (for outer / inner cleaning)) + (Sipper nozzle suction volume: 450 μL (for outer / inner cleaning)) + (Vacuum nozzle immersion volume (for outer cleaning)) < Heated cleaning solution discharge volume...Heated cleaning solution volume (1). An excessively large heated cleaning solution volume (1) leads to increased consumption of cleaning solution. Therefore, by setting the supply volume so that the contaminated area of ​​each nozzle is cleaned by +1 mm, for example, by supplying heated cleaning solution so that the liquid level is +1 mm higher than the 550 μL required to clean the dilution tank, the contaminated area can be cleaned reliably and the cleaning solution can be used without waste. Furthermore, if the dilution tank is narrow, when the sample probe 14, sipper nozzle 13, and vacuum nozzle 26 are immersed in the cleaning solution supplied to the dilution tank 11, the liquid level of the cleaning solution rises by the volume of each nozzle immersed. Therefore, the cleaning solution discharge volume can be controlled to take this increase into account. The diameter of the dilution tank is about 15 mm, and the amount of cleaning liquid for a liquid height of 1 mm is 176 μL, so even when a syringe is used as the liquid delivery means, the liquid level can be sufficiently controlled to 1 mm.

[0041] Next, we will explain the process of supplying heated cleaning solution to the dilution tank 11, followed by lowering the sample probe 14, sipper nozzle 13, and vacuum nozzle 26 for immersion cleaning. While the sample probe 14, sipper nozzle 13, and vacuum nozzle 26 are configured to be able to descend to the bottom of the dilution tank 11, each nozzle is designed to have a fixed contact area with the sample. For example, the sample probe 14 is plunged approximately 3 mm below the liquid surface of the dilution tank 11, while the sipper nozzle 13 and vacuum nozzle 26 are plunged approximately 4 mm after contacting the liquid surface and descending while sucking. Therefore, if each nozzle is lowered to the bottom of the dilution tank 11 containing cleaning solution, the cleaning solution will adhere to the uncontaminated areas of each nozzle, leading to increased consumption of system water and internal standard solution during the rinsing process. Therefore, it is best to control the descent of the sample probe 14, sipper nozzle 13, and vacuum nozzle 26 so that the cleaning solution surface is, for example, +1 mm above the contaminated area of ​​each nozzle.

[0042] In S102, the sample probe 14, the shipper nozzle 13, and the vacuum nozzle 26 are lowered to the level of the heated cleaning liquid dispensed into the dilution tank 11. The sample probe 14 has a function for detecting the liquid level when aspirating a specimen, and by utilizing this function during cleaning, the sample probe 14 can be lowered to the level of the heated cleaning liquid supplied to the dilution tank 11. The lowering operation of the shipper nozzle 13 and the vacuum nozzle 26 can be controlled by pulse movement of a stepping motor, and therefore, by storing parameters for the liquid level of the heated cleaning liquid dispensed into the dilution tank 11 in the control unit of the device, the sample probe 14 can be lowered to the level of the cleaning liquid.

[0043] In S103, the sample probe 14, the shipper nozzle 13, and the vacuum nozzle 26 are lowered to a depth of the contamination range + 1 mm from the surface of the heated cleaning liquid. At this time, it is advisable to lower them while aspirating the cleaning liquid in the dilution tank 11. It is also possible to aspirate the cleaning liquid after lowering each nozzle so that the contamination range outside each nozzle is + 1 mm. However, if aspirating is performed after lowering each nozzle, the liquid level of the cleaning liquid in the dilution tank 11 will decrease, and it may not be possible to ensure the required cleaning range for each nozzle.

[0044] If the amount of lowering were to be increased in advance to account for the drop in the heated cleaning liquid level due to suction from each nozzle, each nozzle would need to be immersed deeper in the cleaning liquid in the dilution tank 11, which could result in the heated cleaning liquid adhering to the nozzle beyond its contamination range. Furthermore, as mentioned above, depending on the shape of the dilution tank 11, the volume of each nozzle may also affect the cleaning liquid, which could result in the cleaning liquid adhering to the nozzle beyond its cleaning range. Therefore, by performing the subsequent lowering operation in S103 while suctioning the cleaning liquid so that the level is 1 mm above the contamination range of each nozzle, it is possible to suppress the cleaning liquid level in the dilution tank 11 and perform cleaning while maintaining the appropriate cleaning range of the dilution tank 11 and each nozzle. Furthermore, by simultaneously lowering each nozzle and suctioning the cleaning liquid, the operation time can be shortened.

[0045] As a means of achieving a similar effect without lowering while suctioning, first, a cleaning solution for cleaning the dilution tank 11 is discharged into the dilution tank 11, and the sample probe 14, shipper nozzle 13, and vacuum nozzle 26 are immersed to a depth of 1 mm beyond the contaminated area. Then, by simultaneously discharging the sample probe 14 and shipper nozzle 13 aspirating the cleaning solution and discharging the same amount of cleaning solution into the dilution tank 11 from the temperature control unit, each nozzle can be cleaned while maintaining the required cleaning area. Therefore, the timing of discharging the heated cleaning solution into the dilution tank 11 can be changed.

[0046] In S104, the sample probe 14 and the shipper nozzle 13 discharge the aspirated cleaning liquid into the dilution tank 11 after cleaning is complete, while rising to a height where they do not come into contact with the cleaning liquid surface in the dilution tank 11. If the aspirated cleaning liquid were discharged without rising, the cleaning liquid surface height in the dilution tank 11 would rise by the amount of liquid, and it is thought that the cleaning liquid would adhere beyond the cleaning range of each nozzle. In order to aspirate and discard the cleaning liquid after cleaning, the vacuum nozzle 26 is raised by the amount of the cleaning liquid surface height that rose when the sample probe 14 and the shipper nozzle 13 discharged it into the dilution tank 11.

[0047] In S105, the vacuum nozzle 26 descends while sucking the cleaning liquid from the dilution tank 11, thereby making it possible to discard the cleaning liquid in the dilution tank 11 that has been used for cleaning while controlling the cleaning range of the vacuum nozzle 26. The vacuum nozzle 26 descends to the bottom of the dilution tank 11, and then ascends after sucking all of the cleaning liquid from the dilution tank 11.

[0048] As shown in Figure 3, by simultaneously cleaning the dilution tank 11, sample probe 14, shipper nozzle 13, and vacuum nozzle 26, all objects to be cleaned can be cleaned with a high-temperature cleaning solution. After the cleaning solution heated by the temperature control unit is discharged into the dilution tank 11, the temperature of the cleaning solution in the dilution tank 11 decreases. Therefore, when cleaning each nozzle by lowering it one by one, the temperature of the cleaning solution used for cleaning becomes (the first nozzle immersed in the cleaning solution) > (the second nozzle immersed in the cleaning solution) > (the third nozzle immersed in the cleaning solution), and the temperature of the cleaning solution used decreases as the nozzle is lowered. To suppress variations in the cleaning effect of each nozzle due to a decrease in the temperature of the cleaning solution, when cleaning three nozzles simultaneously, it is preferable to lower all of them at the same time rather than lowering them one by one.

[0049] 4 shows a time chart for simultaneously rinsing the dilution tank 11, sample probe 14, sipper nozzle 13, and vacuum nozzle 26. The rinsing process is performed in a rinsing process (1) using system water and a rinsing process (2) using an internal standard solution. First, system water is used to clean the dilution tank 11 and sipper nozzle 13 to remove any remaining heated cleaning solution, and then the internal standard solution is used for rinsing, thereby preparing the dilution tank 11 and sipper nozzle 13 for sample measurement.

[0050] In S201, the system water supplied from the second flow path 56 is discharged into the dilution tank 11. The amount of system water discharged here is greater than the amount of heated cleaning liquid (1) in order to reliably rinse off the heated cleaning liquid that has cleaned the dilution tank 11, sample probe 14, shipper nozzle 13, and vacuum nozzle 26. Therefore, the amount of system water discharged into the dilution tank 11 when rinsing all of them simultaneously is as follows:

[0051] Amount of heated cleaning liquid (1) < Amount of system water discharged... Amount of rinsing (1) Rinsing can be achieved by discharging more system water than the heated cleaning area, but there is no need to rinse beyond the area where heated cleaning liquid will not adhere. Rinsing more than necessary leads to an increase in the amount of system water used. Therefore, it is recommended to control the amount of system water discharged so that the area to be rinsed with system water has a liquid level height of the area washed with heated cleaning liquid + 1 mm.

[0052] As described above, a fixed amount of system water can be discharged to the dilution tank 11 by using, for example, a syringe to supply the system water. A second flow path 56 for supplying the system water is connected to a water supply tank 58, and the flow path is equipped with a syringe 46 and solenoid valves 44 and 45. First, the solenoid valve 44 is opened, and the syringe 46 is operated to draw in system water from the water supply tank 58. Then, the solenoid valve 44 is closed, the solenoid valve 45 is opened, and the syringe 46 is operated, thereby discharging a fixed amount of system water to the dilution tank 11. Alternatively, the system water flow path is generally equipped with a magnetic pump 47 that uses water pressure to deliver system water to locations where it is needed. Therefore, the discharge amount may be controlled using the water pressure of the magnetic pump 47, the opening and closing of the solenoid valves 44 and 45, and the throttle 48, without using the syringe 46. When the magnetic pump 47 is used, only one solenoid valve is required. Although the system water delivered from the magnetic pump 47 can be delivered to the dilution tank 11 by opening the solenoid valve, depending on the strength of the water supply pressure, it is possible that the system water may splash or be excessively discharged when it is discharged into the dilution tank 11. Therefore, by providing a restrictor 48 between the solenoid valve and the temperature control unit, it is possible to adjust the amount of water discharged, preventing the system water from splashing and excessive discharge even when the water supply pressure is strong. Without the restrictor 48, it is possible that the amount of system water required for rinsing may not be discharged if the water supply pressure is weakened, so when using the magnetic pump 47, it is advisable to provide a restrictor 48 for adjusting the amount of system water discharged.

[0053] In S202, the sample probe 14, the shipper nozzle 13, and the vacuum nozzle 26 are lowered to the liquid level of the system water discharged into the dilution tank 11. As in the cleaning process, the sample probe 14 has a function for detecting the liquid level, and by utilizing this function in the rinsing process (1), the sample probe 14 can be lowered to the liquid level of the system water supplied to the dilution tank 11. The lowering operation of the shipper nozzle 13 and the vacuum nozzle 26 can be controlled by pulse movement of a stepping motor, and therefore, by storing parameters for the liquid level of the system water discharged into the dilution tank 11 in the control unit of the device, the sample probe 14 can be lowered to the liquid level of the system water.

[0054] In S203, the sample probe 14, the shipper nozzle 13, and the vacuum nozzle 26 are lowered to a depth of 1 mm above the surface of the system water. It is preferable to lower the system water in the dilution tank 11 while aspirating it. It is also possible to aspirate the system water after lowering each nozzle so that the heated cleaning range outside each nozzle is 1 mm above the surface. However, aspirating the system water after lowering each nozzle will lower the surface of the system water in the dilution tank 11, potentially preventing the required rinsing range from being achieved. If the lowering distance is increased in advance to account for the drop caused by suction from each nozzle, the system water in the dilution tank 11 must be immersed deeper, which could result in the system water adhering to the nozzles beyond the required rinsing range, resulting in the system water remaining on the nozzles. If system water remains on the nozzles, it could potentially drip into the dilution tank at an unintended time, affecting analytical performance. Therefore, it is preferable to immerse only the area requiring rinsing in the system water.

[0055] Furthermore, as mentioned above, depending on the shape of the dilution tank 11, the volume of each nozzle may also have an effect, and there is a possibility that the system water may adhere beyond the rinsing range. Therefore, in the subsequent lowering operation in S203, the system water is lowered while being sucked so that it is 1 mm above the heated cleaning range of each nozzle. This makes it possible to suppress the liquid level of the system water in the dilution tank 11, and enables rinsing while maintaining the rinsing range of the dilution tank 11 and each nozzle appropriately. Furthermore, by performing the lowering and suction simultaneously, the operation time can be shortened.

[0056] As a means of achieving the same effect as in the cleaning process without descending while suctioning, system water for rinsing the dilution tank 11 is first supplied, and the sample probe 14, sipper nozzle 13, and vacuum nozzle 26 are also immersed in the system water. Subsequently, by simultaneously aspirating the system water into the sample probe 14 and sipper nozzle 13, and simultaneously discharging the same amount of system water into the dilution tank 11 from the temperature control unit, the same effect can be achieved while maintaining the required rinsing range for each nozzle. Therefore, the timing of discharging the system water into the dilution tank 11 can also be changed.

[0057] In S204, the sample probe 14 and the sipper nozzle 13 discharge the aspirated system water into the dilution tank 11 after rinsing is complete, while rising to a height where they do not come into contact with the system water in the dilution tank 11. If the aspirated system water were discharged without rising, the liquid level of the system water in the dilution tank 11 would rise by the amount of the discharged liquid, and it is thought that the system water would adhere beyond the rinsing range of each nozzle. To aspirate and discard the system water after rinsing, the vacuum nozzle 26 is raised by the amount of the liquid level that rose when the sample probe 14 and the sipper nozzle 13 discharged it into the dilution tank 11.

[0058] In S205, the vacuum nozzle 26 descends while sucking the system water from the dilution tank 11, thereby disposing of the system water from the dilution tank 11 that has been rinsed while controlling the rinsing range of the vacuum nozzle 26. The vacuum nozzle 26 descends to the bottom of the dilution tank 11, sucks up all of the system water from the dilution tank 11, and then ascends.

[0059] After the rinsing step (1) using system water, a rinsing step (2) using an internal standard solution is performed. The rinsing with the internal standard solution targets the dilution tank 11 and the shipper nozzle 13 to prepare them for sample measurement. Because the sample probe 14 used for dispensing the sample does not use an internal standard solution, the rinsing step (1) for the sample probe 14 may be completed. The vacuum nozzle 26 serves to aspirate the liquid remaining in the dilution tank 11, so it does not need to be rinsed with the internal standard solution; it only needs to operate when aspirating the internal standard solution remaining in the dilution tank 11 after rinsing the dilution tank 11 and the shipper nozzle 13 with the internal standard solution is complete. Therefore, the rinsing step (1) for the vacuum nozzle 26 may also be completed.

[0060] In S206, the internal standard solution used in the rinsing step (2) is discharged from the internal standard solution nozzle 25 into the dilution tank 11. The amount to be discharged is as follows:

[0061] Rinse volume (1) < Internal standard solution discharge volume The rinse volume (1) discharged into the dilution tank 11 in the rinsing step (1) is intended to rinse the dilution tank 11, sample probe 14, shipper nozzle 13, and vacuum nozzle 26. Therefore, the amount of internal standard solution discharged into the dilution tank 11 is determined so that the liquid level is, for example, 1 mm higher than the rinse volume (1), taking into account the sample probe 14 and vacuum nozzle 26, which are not subject to rinsing of the internal standard solution. The internal standard solution is supplied by the internal standard solution syringe 8, so that a fixed amount can be supplied.

[0062] In S207, the lowering operation of the shipper nozzle 13 can be controlled by the pulse movement of the stepping motor, and by storing the parameters of the liquid level height of the internal standard solution discharged into the dilution tank 11 in the control unit of the device, the shipper nozzle 13 can be lowered to the cleaning liquid level height.

[0063] In S208, the shipper nozzle 13 is lowered so that it is immersed to a depth of 1 mm from the liquid level of the internal standard solution to the area to be rinsed with system water. It is preferable to lower the shipper nozzle 13 while aspirating the internal standard solution in the dilution tank 11. The internal standard solution can be aspirated after the shipper nozzle 13 is lowered so that the area outside the shipper nozzle 13 is immersed to a depth of 1 mm beyond the area to be rinsed with system water. However, aspirating the internal standard solution after the shipper nozzle 13 is lowered reduces the liquid level of the internal standard solution in the dilution tank 11, which may prevent the necessary rinsing area from being achieved. If the amount of lowering is increased in advance to account for the reduction due to aspirating, the shipper nozzle 13 must be immersed deeper in the internal standard solution in the dilution tank 11, which may result in the internal standard solution adhering to the shipper nozzle 13 beyond the area required for rinsing. Furthermore, as mentioned above, depending on the shape of the dilution tank 11, the volume of each nozzle may also be affected, which may result in the internal standard solution adhering beyond the rinsing area. Therefore, the lowering operation in S208 lowers the internal standard solution while aspirating it so that the internal standard solution is within the system water rinsing range of the shipper nozzle 13 plus 1 mm, thereby making it possible to suppress the liquid level of the internal standard solution in the dilution tank 11 and perform rinsing while appropriately maintaining the rinsing range of the dilution tank 11 and the shipper nozzle 13. Furthermore, by performing lowering and aspirating simultaneously, the operation time can be shortened.

[0064] In S209, after rinsing, the internal standard solution aspirated by the shipper nozzle 13 is discharged into the dilution tank 11 while rising to a height where it does not come into contact with the internal standard solution. If the internal standard solution aspirated without rising is discharged, the liquid level of the internal standard solution in the dilution tank 11 will rise by the amount of the liquid, and it is thought that the internal standard solution will adhere beyond the rinsing range of the shipper nozzle 13.

[0065] In S210, the vacuum nozzle 26 descends while sucking the internal standard solution from the dilution tank 11, thereby making it possible to discard the rinsed internal standard solution while preventing adhesion of the internal standard solution to the vacuum nozzle 26. The vacuum nozzle 26 descends to the bottom of the dilution tank 11, sucks up all of the internal standard solution from the dilution tank 11, and then ascends.

[0066] When the rinsing step (2) is completed, the cleaning of the dilution tank 11, the sample probe 14, the shipper nozzle 13, and the vacuum nozzle 26 is completed.

[0067] In FIG. 3 , the dilution tank 11, sample probe 14, sipper nozzle 13, and vacuum nozzle 26 are all simultaneously cleaned, but the cleaning targets may be changed as desired. For example, as shown in FIG. 5 , the cleaning targets and cleaning cycles for each can be set on a display unit (not shown). Because diluted specimens adhere to the sipper nozzle 13 and vacuum nozzle 26, while undiluted specimens adhere to the sample probe 14 and dilution tank 11, the dilution tank 11 and sample probe 14 may be considered to be more soiled. Therefore, the dilution tank 11 and sample probe 14 may be cleaned daily, while the sipper nozzle 13 and vacuum nozzle 26 may be cleaned once a week. Changing the cleaning targets and cleaning cycles can reduce the amount of cleaning solution consumed and shorten the maintenance time spent on cleaning.

[0068] Examples of cleaning timing include when the device is shut down or when it is started up. Cleaning at either timing will be similar to the cleaning that has been performed manually by the user until now. Preferably, cleaning should be performed when the device is shut down, since cleaning can begin on the same day and the adhesion and accumulation of dirt can be further suppressed. Furthermore, assuming operation without shutting down the device, although not shown in the figure, the control unit may be configured to determine when no sample measurement request has been received (the device is in the standby state described above) and automatically clean the dilution tank 11 and each nozzle.

[0069] Furthermore, since the sample probe 14 generally has a dedicated washing tank (not shown) for the sample probe, only the dilution tank 11, the shipper nozzle 13, and the vacuum nozzle 26 may be washed and rinsed using the dilution tank 11, and the sample probe 14 may be washed and rinsed in a dedicated washing tank. Depending on the setting of the object to be washed and the washing cycle, the amounts of the washing liquid, system water, and internal standard solution used for washing and rinsing shown in Figures 3 and 4 are optimized by the control unit.

[0070] 6 is a flowchart of re-cleaning during an ISE check operation. Before analyzing an ISE item, an ISE check operation is performed to determine whether the ISE unit is in a state where it can be analyzed (S301). The ISE check operation (also called an "instrument health check") is an operation in which the control unit determines whether the ion concentration of the internal standard solution is within a preset normal concentration range. If the concentration of the internal standard solution differs significantly from the design value, it is considered that the instrument is in an irregular state, and if an analysis of a general sample is performed in that state, analytical accuracy may not be guaranteed. Therefore, if it is determined that the concentration is outside the normal concentration range, the analysis operation is generally stopped. This is called an "instrument health check."

[0071] If the ISE check operation determines that an abnormality exists, the probable cause is displayed on a screen (not shown) using an alarm or other means to notify the user. If the ISE check results indicate an abnormality, one possible cause is contamination of the dilution tank 11 and the shipper nozzle 13. Therefore, if an abnormality is determined, cleaning of the dilution tank 11 and the shipper nozzle 13 is automatically initiated (S302), and the ISE check operation is performed again to confirm whether the ISE unit is in a state where analysis is possible (S303). If the device can be recovered from the abnormal state by cleaning, the device can continue to be used (S304), thereby eliminating the need for the user to perform cleaning. If the device cannot be recovered from the abnormal state, the control unit determines that the abnormality is the result of a different problem, and the device notifies the user of the abnormal state by an alarm or other means on a display (not shown) (S305).

[0072] In Example 1, a diluted cleaning solution can be used by discharging system water from the discharge nozzle of the temperature control unit into the cleaning solution in the dilution tank 11. Because the temperature control unit can adjust the temperature of the cleaning solution, when using diluted cleaning solution, it is preferable to increase the temperature of the cleaning solution in advance so that the high temperature can be maintained even after dilution. Diluted cleaning solution is expected to be used, for example, when the cleaning interval is short and the cleaning target is expected to have little contamination, for cleaning the shipper nozzle 13 and vacuum nozzle 26 to which diluted samples are attached, or for cleaning the dilution tank 11, which is expected to have little contamination because it is cleaned with an internal standard solution between sample measurements. Therefore, by providing a flow path for supplying system water to the temperature control unit, not only can crystallization be washed away, but also cleaning using diluted cleaning solution is possible.

[0073] Generally, when cleaning the ion selective electrode 1, a detergent other than the cleaning liquid described in this embodiment is often used. Therefore, when the heated cleaning liquid is sucked into the shipper nozzle 13 to clean the inside, it is desirable to suck it up to just before the ion selective electrode 1 and not pass the heated cleaning liquid through the inside of the ion selective electrode 1. Therefore, it is preferable to return the heated cleaning liquid sucked into the shipper nozzle 13 to the dilution tank 11 for cleaning.

[0074] On the other hand, although not shown, by pressing the maintenance button for flow path cleaning on the display unit, it is possible to clean the flow path on the shipper nozzle 13 side as well. After pressing the maintenance button, the ion selective electrode 1 is replaced with a dummy electrode. Thereafter, it is no longer necessary to return the heated cleaning solution to the dilution tank 11 as explained above, and it is possible to clean not only the inside of the shipper nozzle 13 but also the entire flow path of the shipper nozzle 13.

[0075] The present invention is not limited to the above-described embodiment, but various modifications and applications are possible, and the present invention is not necessarily limited to all of the configurations described above.

[0076] 1: Ion selective electrode, 2: Reference electrode, 3: Internal standard solution bottle, 4: Dilution solution bottle, 5: Reference electrode solution bottle, 6: Suction nozzle, 7: Degassing mechanism, 8: Internal standard solution syringe (liquid delivery part), 9: Dilution solution syringe (liquid delivery part), 10: Sipper syringe (liquid delivery part), 11: Dilution tank, 12: Preheat, 13: Sipper nozzle, 14: Sample probe, 15: Sample container, 16: Filter, 17-22, 30- 32: Solenoid valve (liquid delivery section), 23: Pinch valve, 24: Dilution solution nozzle, 25: Internal standard solution nozzle, 26: Vacuum nozzle, 27: Voltmeter, 28: Amplifier, 29: Control device (judgment section, control section), 33: Vacuum pump, 34: Vacuum bottle, 35: Waste liquid receiver, 36: Waste liquid nozzle, 40: Temperature control section, 41, 42: Solenoid valve, 43: Syringe, 44, 45: Solenoid valve, 46: Syringe, 47: Magnetic pump, 48: Squeeze.

Claims

1. An automatic analyzer comprising: a dilution tank for diluting a sample; a cleaning liquid container for containing a cleaning liquid used to clean the dilution tank; a flow path connecting the cleaning liquid container to a discharge nozzle that discharges the cleaning liquid into the dilution tank; a heating unit that is in direct or indirect contact with the flow path and heats the cleaning liquid flowing through the flow path; and an electrolyte measuring unit having an ion selective electrode that measures the ion concentration in the sample diluted in the dilution tank, wherein the automatic analyzer further comprises a control unit that, when the cleaning liquid is supplied to the dilution tank, controls the heating unit so that the temperature of the cleaning liquid held in the cleaning liquid container becomes a predetermined temperature when the cleaning liquid is discharged into the dilution tank through the flow path and the discharge nozzle.

2. An automatic analyzer according to claim 1, comprising: a water supply container for storing water to be supplied to the dilution tank through the discharge nozzle; and a switching valve for switching between flowing the cleaning liquid supplied from the cleaning liquid container into the discharge nozzle or flowing water supplied from the water supply container into the discharge nozzle, wherein the control unit controls the switching of the switching valve.

3. An automatic analyzer according to claim 2, wherein the switching valve is disposed in a flow path connecting the discharge nozzle and the flow path that is in direct or indirect contact with the heating unit.

4. An automatic analyzer according to claim 1, comprising: a sample probe that ejects the sample into the dilution tank; a vacuum nozzle that discharges the liquid in the dilution tank; and a sipper nozzle that supplies the sample diluted in the dilution tank to the ion selective electrode, wherein the control unit controls the sample probe, vacuum nozzle, and sipper nozzle to be immersed in the cleaning liquid in the dilution tank that contains the cleaning liquid supplied from the cleaning liquid container, and to soak and wash them.

5. An automatic analyzer according to claim 4, wherein at least one of the sample probe, the vacuum nozzle and the shipper nozzle is immersed in the cleaning liquid in the dilution tank and, when soaking and washing them, the control unit controls the sample probe, the vacuum nozzle and the shipper nozzle immersed in the cleaning liquid to suck the cleaning liquid from the dilution tank through them, and then soak and wash them.

6. An automatic analyzer according to claim 5, wherein, when the cleaning liquid in the dilution tank is sucked from the sample probe, the vacuum nozzle, and the shipper nozzle immersed in the cleaning liquid and then soaked and washed, the control unit controls the amount of cleaning liquid discharged from the discharge nozzle into the dilution tank so that it does not fall below the cleaning target range of the dilution tank even after the cleaning liquid in the dilution tank is sucked from the sample probe, the vacuum nozzle, and the shipper nozzle.

7. An automatic analyzer according to claim 1, wherein, when the control unit determines that the ion concentration of the internal standard solution is outside a preset normal concentration range, the control unit controls the device to automatically start an operation of discharging the cleaning solution from the cleaning solution container into the dilution tank and cleaning the dilution tank.

8. An automatic analyzer according to claim 1, wherein the control unit controls the heating unit so that the temperature of the cleaning liquid is between 40°C and 70°C.

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