Analysis device

Abstract

The following configuration is used in order to provide an analysis device which will prevent the concentration of a reagent from diminishing, even with a device configuration in which a single shared quantifier (e.g., a syringe pump) is used to quantify a high-concentration reagent and a diluted liquid, and in which the reagent is discharged into a container for measurement or for dilution through a shared reagent flow path.　This analysis device comprises a control unit that, after a prepared reagent is discharged from a prepared reagent discharge nozzle into a dilution tank, controls a valve connected to a third flow path to be opened for a prescribed length of time in order to release the pressure in the third flow path before the start of analysis of the next prepared reagent in the dilution tank.

Description

Analyzer

[0001] The present invention relates to an analyzer, and more particularly to a medical analyzer such as an electrolyte analyzer or an automatic blood cell counter.

[0002] The present invention is applicable to an analyzer that carries out an analysis by sending a liquid such as a reagent to each part through a flow path, and the following description will be given taking an electrolyte analyzer as an example of such an analyzer.

[0003] An electrolyte analyzer measures the concentration of specific electrolytes contained in electrolyte solutions such as human blood and urine, and uses an ion-selective electrode to measure the concentration. A flow-type electrolyte analyzer is one example of an electrolyte analyzer. In a flow-type electrolyte analyzer, serum as an electrolyte solution, either directly or diluted with a sample diluent, is supplied to an ion-selective electrode, and the liquid junction potential between the ion-selective electrode and the reference electrode solution is measured. Subsequently (or prior to measurement), a standard solution with a known electrolyte concentration is supplied to the ion-selective electrode, and the liquid junction potential between the ion-selective electrode and the reference electrode solution is measured in the same manner as for serum (or the sample solution). The electrolyte concentration of the serum (or the sample solution) can then be calculated from the two liquid junction potentials: the liquid junction potential of the standard solution and the liquid junction potential of the serum (or the sample solution).

[0004] In such flow-type electrolyte analyzers, reagents such as sample dilution solutions, standard solutions, and reference electrode solutions are used as consumables, and the amounts of these reagents used per analysis are determined by arbitrarily set analytical parameters. Furthermore, these reagents are supplied from individually replaceable reagent containers (e.g., 2-liter bottles). As the number of test instruments and test samples increases, the number and frequency of reagent bottle replacements increases, placing a heavy burden on operators. Furthermore, with conventional analyzers, bottle replacements are required every few hours during continuous operation, placing operators on a time schedule for reagent bottle replacements. Furthermore, standard solutions, in particular, are reagents that serve as analytical standards, and even minute changes in their concentration can affect analytical values, requiring recalibration after bottle replacement. The downtime associated with bottle replacements and subsequent calibration reduces the actual analytical throughput.

[0005] In response to these problems, Patent Document 1 discloses an electrolyte analyzer including: a high-concentration reagent bottle containing a high-concentration reagent; a reagent dilution bottle containing a reagent dilution solution for diluting the high-concentration reagent; a first flow path for delivering the high-concentration reagent from the high-concentration reagent bottle; a second flow path for delivering the reagent dilution solution from the reagent dilution solution bottle; a confluence section for joining the first flow path and the second flow path; a third flow path for delivering a prepared reagent, which is a mixture of the high-concentration reagent and the reagent dilution solution, from the confluence section; a dilution tank containing the prepared reagent; a prepared reagent discharge nozzle for discharging the prepared reagent delivered through the third flow path into the dilution tank; a liquid delivery mechanism for delivering the high-concentration reagent and the reagent dilution solution to the branching section at a predetermined ratio so that the prepared reagent discharged from the prepared reagent discharge nozzle into the dilution tank via the third flow path has a predetermined concentration; and an analysis section for performing analysis using the prepared reagent contained in the dilution tank.

[0006] International Publication No. 2021 / 140796

[0007] In the above-mentioned conventional technology, in order to enable more accurate dilution and preparation of a reagent with a simpler device configuration, a single common metering device (such as a syringe pump) is used to measure the amounts of a high-concentration reagent and a diluent, and the measured amounts are then discharged into a measurement or dilution container through a common reagent flow path. While examining the above-mentioned conventional technology, the inventors have newly discovered the following problems.

[0008] In the above configuration, in order to measure and dispense multiple reagents using a common dispenser, solenoid valves are provided to control the movement of each reagent and solenoid valves to control the discharge. When all of the solenoid valves are closed, the flow path surrounded by the solenoid valves becomes a closed flow path. Meanwhile, the analyzer uses motors, solenoid valves, and circuit boards to dispense reagents and samples. When an analysis operation begins, the temperature inside the analyzer gradually rises, and the temperature of the above-mentioned closed flow path also rises. As the temperature of the reagents in the flow path rises, the pressure inside the closed flow path rises.

[0009] When the solenoid valve for aspirating the high-concentration reagent is opened after the internal pressure of the closed flow path rises, the pressure is relieved, and some of the diluent in the closed flow path flows back into the flow path connected to the high-concentration reagent container. Because the meter is designed to perform the aspirating operation on the assumption that the flow path is filled with the high-concentration reagent, it was found that if part of the flow path is replaced with the diluent, the amount of high-concentration reagent aspirated decreases, resulting in a phenomenon in which the concentration of the reagent used for analysis decreases (becomes less diluted than the specified value).

[0010] The object of the present invention is to provide an analytical device that does not cause dilution of the reagent concentration, even if the device is configured to use a single common meter (such as a syringe pump) to measure the amount of high-concentration reagent and dilution solution, and then discharge them into a measurement or dilution container through a common reagent flow path.

[0011] The present application includes a number of means for solving the above problems, examples of which are as follows.

[0012] a high-concentration reagent bottle containing a high-concentration reagent; a reagent dilution bottle containing a reagent dilution liquid for diluting the high-concentration reagent; a first flow path for sending the high-concentration reagent from the high-concentration reagent bottle; a second flow path for sending the reagent dilution liquid from the reagent dilution liquid bottle; a junction for joining the first flow path and the second flow path; a third flow path for sending a prepared reagent which is a mixture of the high-concentration reagent and the reagent dilution liquid from the junction; a dilution tank containing the prepared reagent; a prepared reagent discharge nozzle for discharging the prepared reagent sent through the third flow path into the dilution tank; The analytical device includes a liquid delivery mechanism that delivers high-concentration reagent and reagent dilution liquid to a confluence at a predetermined ratio so that the prepared reagent discharged from the prepared reagent discharge nozzle into the dilution tank via the flow path has a predetermined concentration, and an analysis unit that performs analysis using the prepared reagent contained in the dilution tank, and a control unit that controls a valve connected to the third flow path to open for a predetermined time after the prepared reagent is discharged from the prepared reagent discharge nozzle into the dilution tank and before the start of analysis of the next prepared reagent in the dilution tank, in order to release the pressure in the third flow path.

[0013] An analytical device can be provided that does not dilute the reagent concentration, even if the device is configured to use a single common meter (such as a syringe pump) to measure the amount of high-concentration reagent and dilution solution and then eject them into a measurement or dilution container through a common reagent flow path.

[0014] 1 is a diagram showing an outline of the overall configuration of an electrolyte analyzer according to a first embodiment. FIG. 2 is a diagram showing the reagent preparation unit according to the first embodiment together with related configurations. FIG. 3 is a timing chart illustrating a conventional reagent supply operation in one cycle of the reagent preparation unit. FIG. 4 is a diagram showing the electromotive force of an internal standard solution measured in a conventional reagent supply operation. FIG. 5 is a timing chart illustrating a reagent supply operation in one cycle of the reagent preparation unit according to the first embodiment. FIG. 6 is a diagram showing the electromotive force of an internal standard solution measured in a reagent supply operation according to the first embodiment. FIG. 7 is a diagram showing a schematic view of the internal state of a third flow path 43 after a liquid delivery operation. FIG. 8 is a diagram showing a schematic view of the internal state of a third flow path 43 after a liquid delivery operation. FIG. 9 is a diagram showing a schematic view of the internal state of a third flow path 43 after a liquid delivery operation. FIG. 10 is a diagram showing a schematic view of the internal state of a third flow path 43 after a liquid delivery operation. FIG. 11 is a diagram showing a schematic view of the internal state of a third flow path 43 after a liquid delivery operation. FIG. 12 is a diagram showing a schematic view of the internal state of a third flow path 43 after a liquid delivery operation. FIG. 13 is a diagram showing a schematic view of the internal state of a third flow path 43 after a liquid delivery operation. 17 is a diagram showing another example of a liquid delivery mechanism (liquid delivery syringe) having a function of stirring an internal liquid in association with a liquid delivery operation. FIG. 18 is a diagram showing a modified example of a confluence section. FIG. 19 is a diagram showing another modified example of a confluence section. FIG. 19 is a schematic diagram showing a reagent preparation section provided with a flow path for releasing atmospheric pressure and a solenoid valve in a reagent flow path. FIG. 19 is a diagram showing a timing chart for explaining a reagent supply operation in the configuration of FIG. 16. FIG. 19 is a diagram showing the reagent preparation section according to a second embodiment together with related configurations. FIG. 19 is a diagram showing a timing chart for explaining a reagent supply operation in the configuration of FIG. 18. FIG. 19 is a diagram showing a modified example of the timing chart of FIG. 19.

[0015] Hereinafter, an embodiment of the present invention will be described with reference to the drawings.

[0016] A first embodiment of the present invention will be described with reference to the drawings. Fig. 1 is a diagram schematically illustrating the overall configuration of an analyzer according to an embodiment of the present invention. In this embodiment, an electrolyte analyzer, specifically a flow-type electrolyte analyzer (hereinafter simply referred to as an electrolyte analyzer) using ion selective electrodes (hereinafter referred to as ISE electrodes), will be shown and described as an example of the analyzer.

[0017] In FIG. 1, the electrolyte analyzer 100 is generally composed of a sample dispensing section 101, an ISE electrode section 102, a reagent section 103, a reference electrode solution supply section 104, a specimen dilution solution supply section 105, a reagent preparation section 106, a waste liquid mechanism 107, and a control device 29.

[0018] The sample dispensing unit 101 includes a sample probe 14 and a sample container 15. The sample probe 14 dispenses a sample (such as a patient's specimen) held in the sample container 15 and draws it into the automated analyzer. Here, the specimen is an object to be analyzed that is 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 or dilution.

[0019] The ISE electrode section 102 includes a dilution tank 11, a sipper nozzle 13, an ISE electrode 1, a reference electrode 2, a voltmeter 27, and an amplifier 28. The sample dispensed by the sample dispenser is discharged into the dilution tank 11, where it is diluted and stirred with the specimen dilution solution dispensed into the dilution tank 11 from a specimen dilution solution dispense nozzle 24. The sipper nozzle 13 is connected to the ISE electrode 1 by a flow path, and the diluted sample solution aspirated from the dilution tank 11 is delivered to the ISE electrode 1 by this flow path. Here, the ISE electrode section 102, together with the control device 29, constitutes an analysis section that analyzes the sample using the prepared reagent contained in the dilution tank 11.

[0020] The reagent section 103 includes the reagents required for measurement, reagent bottles containing the reagents, and a reagent suction nozzle 8 for aspirating the reagents from the reagent bottles. The reagent section 103 may also include a degassing mechanism 7 for removing gaseous components contained in the reagent under vacuum, a filter 16, and the like. Four types of liquids are used as the reagents for electrolyte measurement: a high-concentration reagent, a reagent dilution solution, a specimen dilution solution, and a reference electrode solution. In this embodiment, for example, the high-concentration reagent is an internal standard solution having a concentration several tens of times higher than normal, and the reagent dilution solution is pure water.

[0021] In this embodiment, a high-concentration reagent bottle 3 containing a high-concentration reagent, a reagent diluent bottle 4 containing a reagent diluent, a specimen diluent bottle 5 containing a specimen diluent, and a reference electrode solution bottle 6 containing a reference electrode solution are set in the reagent section 103. The reagent diluent bottle 4 containing the reagent diluent may be configured to automatically supply pure water directly from a pure water production machine, in which case replacement of the reagent diluent bottle 4 is not required during operation of the device. Furthermore, when cleaning the flow paths and the like within the device, a cleaning solution bottle containing a cleaning solution may be set in the reagent section.

[0022] The degassing mechanism 7 is a mechanism that prevents air bubbles from appearing in the reagent from being supplied directly to the dilution tank 11 or the reference electrode 2. The syringes used to deliver each reagent create negative pressure in the flow path to draw up the reagent from each bottle, which can cause gas dissolved in the reagent to appear as bubbles in the reagent. If air bubbles form in the flow path, they can collapse and act as a cushion even when the syringe pump is operated, potentially preventing the desired reagent from being dispensed. The degassing mechanism 7 prevents air bubbles from entering the reagent and being supplied to the dilution tank 11 or the reference electrode 2. The filter 16 is a mechanism that traps impurities (such as dust) contained in the reagent bottles.

[0023] The reference electrode solution supply unit 104 includes a sipper syringe 10, a pinch valve 23, and solenoid valves 17, 21, and 22, and is responsible for the operation of supplying the reference electrode solution and the operation of supplying the sample solution to the ISE electrode. The reference electrode solution contained in the reference electrode solution bottle 6 is supplied 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 supplied to the ISE electrode flow path and the reference electrode solution supplied to the reference electrode flow path come into contact, establishing electrical continuity between the ISE electrode 1 and the reference electrode 2. The ISE electrode unit measures the concentration of a specific electrolyte contained in the sample based on the potential difference (liquid junction potential) between the ISE electrode 1 and the reference electrode 2.

[0024] Specifically, for example, an ion-sensitive membrane is attached to the ISE electrode 1, whose electromotive force changes depending on the concentration of specific ions (e.g., sodium ions (Na+), potassium ions (K+), chloride ions (Cl-), etc.) in the sample solution. This causes the ISE 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 ISE electrode 1 and the reference electrode 2. The control device 29 calculates the ion concentration in the specimen from the electromotive force acquired for each ion and outputs (for example, displays) the result. The sample solution remaining in the dilution tank 11 is discharged by a waste liquid mechanism, which will be described later.

[0025] The specimen dilution liquid supply unit 105 includes a specimen dilution liquid syringe 9, solenoid valves 18 and 20, and a specimen dilution liquid discharge nozzle 24. The specimen dilution liquid discharge nozzle 24 is installed with its tip inserted into the dilution tank 11 and is connected to the specimen dilution liquid bottle 5 through a flow path. A preheat 12 may be included in the flow path. The preheat 12 is a mechanism for suppressing the effect of temperature on the ISE electrode 1 by controlling the temperature of the reagent reaching the ISE electrode 1 within a certain range.

[0026] The reagent preparation unit 106 has a function of diluting the high-concentration reagent contained in the high-concentration reagent bottle 3 with the reagent dilution solution contained in the reagent dilution solution bottle 4 by mixing them together to prepare a reagent (prepared reagent) at a predetermined concentration. The detailed configuration and operation of the reagent preparation unit 106 will be described later.

[0027] The waste liquid mechanism includes a first waste liquid nozzle 26, a second waste liquid nozzle 30, 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 remaining in the flow path of the ISE electrode section 102.

[0028] Although not shown, the control device 29 controls the overall operation of the electrolyte analyzer and can be configured as a computer equipped with a calculation means such as a central processing unit (CPU), a storage means such as a random access memory (RAM), 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 are 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. 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. The program is loaded into the storage means and executed by the calculation means. An input / output device may also 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] Here, the basic operation of measuring electrolyte concentration in the electrolyte analyzer 100 will be described. The measurement operation in the electrolyte analyzer 100 is controlled by the control device 29. The control device 29 first dispenses the sample dispensed from the sample container 15 using the sample probe 14 of the sample dispenser into the dilution tank 11 of the ISE electrode. Then, the sample dilution syringe 9 operates to dispense the sample dilution from the sample dilution bottle 5 into the dilution tank 11 via the sample dilution nozzle 24. The sample is diluted with the sample dilution in the dilution tank 11. As described above, to prevent the generation of bubbles due to temperature and pressure changes in the sample dilution in the flow path, a degassing process may be performed using the degassing mechanism 7 installed midway along the sample dilution flow path. The diluted sample solution is then delivered to the ISE electrode 1 by the operation of the sipper syringe 10.

[0030] Meanwhile, the pinch valve 23 and the sipper syringe 10 operate to send the reference electrode solution from the reference electrode solution bottle 6 to the reference electrode 2. 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 with each other, thereby establishing electrical continuity between the ISE 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.

[0031] To suppress the effects of concentration fluctuations while the sample solution is being delivered, it is desirable to use a high electrolyte concentration for the reference electrode solution. The reference electrode solution is, for example, a potassium chloride (KCl) aqueous solution of a predetermined concentration. However, near-saturation concentrations can lead to crystallization of the reagent, potentially causing clogging of 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 and 3.0 mmol / L.

[0032] In addition, before or after the measurement using the sample solution, the electrolyte concentration of the internal standard solution is measured in the same manner as the measurement using the sample solution. In this embodiment, the internal standard solution is prepared by diluting a high-concentration reagent in the reagent preparation unit. The specific operation of the reagent preparation unit will be described later.

[0033] 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 enables more accurate measurement of the electrolyte concentration. The specific calculation content of the calibration process can be designed appropriately by a person skilled in the art based on known techniques, etc.

[0034] The above series of analyses, including dispensing of the sample, measuring the electrolyte of the sample, and measuring the electrolyte of the internal standard solution before and after, is considered one cycle, and one sample is processed per cycle. By repeating the cycle, electrolyte analysis of multiple samples is performed.

[0035] Next, the reagent preparation unit 106 of the electrolyte analyzer 100 will be described in detail. FIG. 2 is a diagram illustrating the reagent preparation unit together with related components. The reagent preparation unit 106 includes a first flow path 41 for delivering a high-concentration reagent from the high-concentration reagent bottle 3, a second flow path 42 for delivering a reagent dilution solution from the reagent dilution solution bottle 4, a confluence 37 where the first flow path 41 and the second flow path 42 merge, a third flow path 43 for delivering a prepared reagent, which is a mixture of a high-concentration reagent and a reagent dilution solution, from the confluence 37, a dilution tank 11 for containing the prepared reagent, a prepared reagent discharge nozzle 25 for discharging the prepared reagent delivered through the third flow path 43 into the dilution tank 11, a liquid delivery syringe 36 constituting a liquid delivery mechanism for delivering the high-concentration reagent and the reagent dilution solution to the confluence 37, and solenoid valves 38, 39, and 40. A preheater 12 is provided in the third flow path 43.

[0036] The liquid supply syringe 36 is provided in the second flow path 42. The confluence 37 has a single branch point, and the first flow path 41, the second flow path 42, and the third flow path 43 connected to the confluence 37 are connected by connectors. The confluence 37 is made of a material with excellent chemical resistance, such as acrylic or vinyl chloride. Furthermore, each of the first flow path 41, the second flow path 42, and the third flow path 43 is made of a resin tube with an inner diameter of 1 mm, for example.

[0037] The reagent preparation unit 106 includes one liquid delivery mechanism (liquid delivery syringe 36) in its flow paths. By operation of the liquid delivery syringe 36 and solenoid valves 38, 39, and 40, a high-concentration reagent is delivered from the first flow path 41 to the junction 37, and a reagent dilution solution is delivered from the second flow path 42 to the junction 37. A mixture of the high-concentration reagent and the reagent dilution solution is delivered from the junction 37 to the third flow path 43. The mixture of the high-concentration reagent and the reagent dilution solution is mixed in the third flow path 43, and finally, a predetermined amount (amount of liquid delivery per cycle) is delivered from the prepared reagent delivery nozzle 25 to the dilution tank 11 as the prepared reagent. The reagent delivered to the dilution tank 11 is stirred in the dilution tank 11 by the force of delivery and is then used for analysis by the analysis unit (ISE electrode unit 102).

[0038] Here, we will first explain the reagent delivery operation in the reagent preparation unit of a conventional electrolyte analyzer. FIG. 3 is a timing chart illustrating one cycle of the reagent delivery operation of the reagent preparation unit, with time indicated on the horizontal axis. As shown in FIG. 3, first, the solenoid valve 39 is opened, and the liquid delivery syringe 36 is operated to draw the high-concentration reagent from the first flow path 41 into the second flow path 42 (STEP 1). Then, the solenoid valve 40 is opened, and the liquid delivery syringe 36 is operated to draw the reagent dilution solution from the reagent dilution solution bottle 4 into the second flow path 42 (STEP 2). Then, the solenoid valve 38 is opened, and the liquid delivery syringe 36 is operated to deliver the high-concentration reagent and the reagent dilution solution to the third flow path 43. A mixture of the high-concentration reagent and the reagent dilution solution (hereinafter simply referred to as the mixture solution) is delivered from the prepared reagent delivery nozzle 25 to the dilution tank 11, driven by the high-concentration reagent and the reagent dilution solution delivered to the third flow path 43. After the prepared reagent has been dispensed, the electromagnetic valve 38 is closed (STEP 3).

[0039] The mixed solution discharged into the dilution tank 11 is sent to the ISE electrode 1 by the operation of the syringe 10, and the ISE electrode potential based on the reference electrode potential is measured using a voltmeter 27 and an amplifier 28.

[0040] In this operation, while the concentration of the internal standard solution is measured after reagent supply and while the concentration of the sample is measured, solenoid valves 38, 39, and 40 are all closed, and first flow path 41, second flow path 42, and part of third flow path 43 are closed. At this time, the temperature inside the device increases the reagent temperature in the closed flow paths, causing an increase in internal pressure. When solenoid valve 39 is opened in the next reagent supply operation, some of the mixed liquid flows back into first flow path 41 to relieve the pressure in the closed flow paths. If this backflow occurs, some of the reagent drawn in during the aspirating operation of the high-concentration reagent in the next reagent supply operation, STEP 1, is replaced by the mixed liquid, preventing the specified amount of high-concentration reagent from being aspirated, resulting in a fluctuation in the concentration of the prepared reagent.

[0041] FIG. 4 shows an example of the electromotive force of the internal standard solution measured during the reagent supply operation shown in FIG. 3. The vertical axis shows the fluctuation in the electromotive force of the measured internal standard solution (the relative fluctuation when the result of the first measurement is set to 0 mV). As the concentration of the internal standard solution decreases, the electromotive force decreases. In the reagent supply operation shown in FIG. 3, the electromotive force decreases as the number of measurements increases. In other words, the concentration of the internal standard solution decreases over time. This is thought to be because as the operating time of the device increases, the temperature inside the device rises, increasing the amount of mixed solution flowing back into the first flow path 41. As the amount of backflow increases, the concentration of the prepared reagent decreases further.

[0042] An embodiment of the present invention has a configuration for preventing this phenomenon, which will be described below. Figure 5 is a timing chart illustrating the reagent supply operation in one cycle of the reagent preparation unit in this embodiment of the present invention. STEPs 1 and 2 are the same as those in Figure 3, and therefore will not be described here. STEP 3 in this embodiment differs from that in Figure 3. The high-concentration reagent and the diluted reagent are delivered to the third flow path 43 by the delivery operation of the liquid delivery syringe 36, with the solenoid valve 38 open. The process is the same as in Figure 3 until the mixed solution in the delivered volume is delivered from the prepared reagent delivery nozzle 25 to the dilution tank 11, pushed by the high-concentration reagent and diluted reagent delivered to the third flow path 43.

[0043] Unlike in FIG. 3 , the solenoid valve 38 remains open until the next reagent supply operation begins. This prevents the flow path enclosed by the solenoid valve from becoming a closed flow path. This prevents the mixed solution from backflowing from the closed flow path, where internal pressure has increased, into the first flow path 41 connected to the high-concentration internal standard solution tank when the solenoid valve 39 is opened for the next reagent supply operation. In this case, if the next reagent supply operation begins relatively quickly, the initial problem of "dilution of the reagent concentration" can be solved by leaving the solenoid valve 38 open. However, if the solenoid valve 38 is left open for a long time, the mixed solution may leak from the prepared reagent discharge nozzle 25 via the flow path. To prevent this, a small amount of air may be sucked from the tip of the prepared reagent discharge nozzle 25 after discharge by performing a suction operation with the liquid supply syringe 36. This air layer prevents the reagent from leaking from the tip of the prepared reagent discharge nozzle 25 even if the mixed solution in the flow path expands due to heat. If the mixture leaks during sample concentration measurement, it may cause an abnormal measurement value.

[0044] 5, the solenoid valve 38 is kept open until the next reagent supply operation begins. However, the effects of the present invention can be achieved by preventing the pressure of the liquid in the flow path enclosed by the solenoid valve from increasing. That is, after the prepared reagent is discharged from the prepared reagent discharge nozzle 25 into the dilution tank 11, the solenoid valve 38 connected to the third flow path 43 can be opened for a predetermined time to release the pressure in the third flow path 43 before the start of the next analysis of the prepared reagent in the dilution tank 11. The solenoid valve 38 should be open for a period of time sufficient to fully release the pressure in the closed flow path, taking into account the volume of the closed flow path (i.e., the length of the flow path that constitutes it multiplied by the cross-sectional area of ​​the flow path piping) and the degree of temperature rise in the analyzer. Furthermore, while the solenoid valve 38 is preferably opened immediately before the start of the next reagent supply, it does not necessarily need to be opened immediately before the start of the next reagent supply, as long as backflow of the mixed liquid into the first flow path 41 can be suppressed to a practically acceptable level. However, if the solenoid valve 38 is operated during measurement of the ISE electrode potential, electromagnetic noise may occur in the measurement data, which may cause abnormal measurement values, so it is desirable to operate it after the potential measurement is completed.

[0045] Figure 6 shows the results of measuring the electromotive force of the internal standard solution measured during the reagent supply operation shown in Figure 5. The vertical axis, as in Figure 4, represents the amount of fluctuation in the electromotive force of the measured internal standard solution. It can be seen that by applying the reagent supply operation shown in Figure 5, it is possible to suppress fluctuations in the concentration of the internal standard solution.

[0046] FIG. 7 is a schematic diagram showing the internal state of the third flow path 43 after the liquid delivery operation. When the reagent preparation unit 106 performs the liquid delivery operation, the high-concentration reagent and the diluted reagent solution are alternately delivered to the third flow path 43 via the confluence 37. For example, if a 30-fold concentrated internal standard solution is used as the high-concentration reagent, a 29-fold volume of diluted reagent solution must be delivered to prepare a normal concentration (1x) internal standard solution (prepared reagent). For example, 15 μL of the high-concentration reagent is delivered to the confluence 37, and 435 μL of diluted reagent solution is delivered to the confluence 37 relative to the high-concentration reagent. The high-concentration reagent and diluted reagent solution are delivered to the third flow path 43 via the confluence 37, forcing out 450 μL of the mixed solution of the high-concentration reagent and diluted reagent solution (prepared reagent) into the dilution tank 11. That is, the liquid delivery mechanism (liquid delivery syringe 36) delivers liquid under the control of the control device 29 so that the prepared reagent discharged from the prepared reagent discharge nozzle 25 to the dilution tank 11 via the third flow path 43 has a predetermined concentration.

[0047] Fig. 8 is a diagram showing a change in concentration of the mixed solution sent to the third flow path during the sending process, and Fig. 9 is a diagram showing the behavior of the high-concentration reagent and the diluted reagent solution in the third flow path during the sending operation.

[0048] As shown in Figure 9, during the liquid transfer operation, the fluid near the inner wall of the pipe moves slower than the fluid near the center of the pipe due to wall resistance, so the liquid near the wall is overtaken by the following liquid near the center of the pipe. That is, the high-concentration reagent and the diluted reagent alternately transferred to the third flow path 43 via the confluence 37 are mixed in the third flow path 43 by a flow (e.g., turbulence) that differs from the liquid transfer direction due to the difference in the transfer speed between the fluid near the inner wall and the center of the pipe. Furthermore, because of the difference in the transfer speed between the fluid near the wall and the fluid near the center of the pipe during the liquid transfer operation, the boundary between the high-concentration reagent and the diluted reagent alternately transferred to the third flow path 43 is stretched in the liquid transfer direction, increasing the contact area between the high-concentration reagent and the diluted reagent.

[0049] This enhances the diffusion action (diffusion of the high-concentration reagent into the diluted reagent) at the contact point between the high-concentration reagent and the diluted reagent, further facilitating mixing of the high-concentration reagent and the diluted reagent. The magnitude of the mixing action of the high-concentration reagent and the diluted reagent depends on the length of the liquid-feeding flow path, and the longer the liquid-feeding flow path, the more the mixing of the high-concentration reagent and the diluted reagent is promoted. Therefore, the longer the liquid-feeding flow path (here, third flow path 43), the more uniform the mixed liquid (prepared reagent) can be obtained.

[0050] 8 shows the concentrations at each cross section of the third flow path 43, where the concentration of the high-concentration reagent is concentration A, the concentration of the diluted reagent is concentration C, and the target concentration is concentration B. As shown in Fig. 8, the high-concentration reagent and the diluted reagent are not yet sufficiently mixed upstream of the third flow path 43 (immediately after the junction 37), and there is a large difference in concentration, but mixing within the flow path is promoted with each liquid transfer process, and the concentrations eventually become uniform.

[0051] Even if the mixed solution delivered to the third flow path 43 is not sufficiently mixed, it is sufficient that the mixed solution has a certain concentration for each volume of analysis, and therefore does not need to have a uniform concentration throughout. In other words, as long as the mixed solution finally delivered to the dilution tank 11 has a certain concentration for each analysis, it is acceptable for the mixed solution immediately before delivery to have a large concentration difference between the high-concentration and low-concentration portions (i.e., concentration unevenness). However, if higher accuracy is required, it is desirable that the two solutions delivered to the third flow path 43 be sufficiently mixed and have a uniform concentration before delivery. This is because sufficient mixing can reduce variation in the amount of high-concentration reagent contained in each volume of analysis. Furthermore, if the mixed solution is sufficiently mixed, slight fluctuations in the amount delivered to the dilution tank do not affect the concentration, thereby increasing the stability of the concentration.

[0052] Because the mixing process in the third flow path 43 depends on the length of the flow path, it is desirable to make the third flow path 43 as long as possible. By making the third flow path 43 long, it is possible to achieve a state in which the mixed liquid is sufficiently mixed before being discharged. In addition, by making the third flow path 43 long, other factors that affect concentration variations, such as variations in the amount of high-concentration reagent aspirated, can be homogenized through the mixing process in the flow path, thereby ensuring reproducibility of the concentration of the mixed liquid finally discharged into the dilution tank 11.

[0053] However, if the flow path is too long, the piping resistance may exceed the driving force of the liquid delivery mechanism, making it impossible to deliver the liquid. Furthermore, even if the same discharge operation is performed, a longer flow path may increase the pressure inside the pipe during the discharge operation, which may exceed the pressure resistance range of the flow path components (e.g., solenoid valves and piping tubes). Therefore, the length of the flow path should be long enough to obtain the desired reproducibility of the measurement results, and should be optimized appropriately for each target value of the measurement results in the target device configuration.

[0054] Furthermore, since the temperature stability of the measurement reagent greatly affects the analysis results in electrolyte analysis, when the flow path is lengthened, it is desirable to lengthen the flow path from the confluence 37 to the outlet of the prepared reagent discharge nozzle 25 before passing through the preheater.

[0055] Here, the sedimentation phenomenon of the high-concentration reagent in the third flow path 43 will be described. In the third flow path 43, immediately after the liquid is delivered, the high-concentration portion and the low-concentration portion (diluted reagent portion) are clearly separated and insufficiently mixed. As time passes in this state, the high-concentration reagent has a higher specific gravity than the diluted reagent, causing the high-concentration reagent to settle downward due to the difference in specific gravity. If the mixture of the high-concentration reagent and diluted reagent remains in an incompletely mixed state in the flow path, the high-concentration reagent will become completely mixed after a long period of time due to natural diffusion of the high-concentration reagent. However, since the diffusion rate of natural diffusion is much slower than the sedimentation rate, the effect of natural diffusion can be ignored in practice. Conversely, sedimentation cannot be ignored because it can be observed even in a short time, such as several seconds to several tens of seconds, after the liquid has settled.

[0056] FIG. 10 is a schematic diagram illustrating an example of the structure of the third flow path. In FIG. 10, the third flow path 43 has a spiral spring-like structure wound with a predetermined radius. This makes it possible to suppress the effects of sedimentation of the high-concentration reagent. With this configuration, even if sedimentation occurs, the high-concentration reagent settles to a lower position within one winding, preventing further progression of the sedimentation phenomenon. This makes it possible to maintain a certain degree of sedimentation even if the operating time changes irregularly, thereby making it possible to maintain the liquid delivery pattern.

[0057] As shown in FIG. 10, the winding direction is preferably such that the axis of rotation faces horizontally (i.e., the winding direction is configured so that the vertical tilt is repeated periodically as the flow path advances). The winding diameter is preferably determined so that the flow path volume per revolution is equal to or less than the amount of liquid delivered in one cycle. While the entire third flow path 43 may be wound, the settling phenomenon of the high-concentration reagent is particularly pronounced in the region where the difference in concentration between the high-concentration portion and the low-concentration portion is large, i.e., the region immediately after the confluence 37 of the third flow path 43. Therefore, only the relevant region of the third flow path 43 may be wound.

[0058] In consideration of the sedimentation phenomenon, it is desirable that the liquid delivery mechanism (here, the liquid delivery syringe 36) provided in the reagent preparation unit 106 is provided in either the first flow path 41 or the second flow path 42. This is to suppress the occurrence of sedimentation of the high-concentration reagent inside the liquid delivery mechanism by minimizing the number of liquid delivery mechanisms in which the sedimentation phenomenon is likely to occur due to the accumulation of a mixture of the high-concentration reagent and the reagent dilution solution inside.

[0059] Furthermore, when the liquid delivery mechanism is provided in the third flow path 43, it is desirable to provide it immediately before the prepared reagent discharge nozzle (discharge port) 25. In this way, the mixed liquid introduced into the third flow path 43 is mixed as much as possible in the flow path before reaching the liquid delivery mechanism, which makes it possible to suppress the effects of sedimentation of high-concentration components in the mixed liquid introduced inside the liquid delivery mechanism.

[0060] Fig. 11 is a diagram showing an example of a liquid delivery mechanism (liquid delivery syringe) having a function of stirring the liquid inside during the liquid delivery operation, and Figs. 12 and 13 are diagrams showing other examples of liquid delivery mechanisms (liquid delivery syringes) having a function of stirring the liquid inside during the liquid delivery operation.

[0061] In the liquid delivery mechanism (liquid delivery syringe) shown in Figure 11, liquid delivery is performed by operating a cylindrical drive plunger 44 using a drive motor (not shown). However, by providing a cylindrical part 45 with a radius larger than that of the drive plunger 44 at the tip of the drive plunger 44, it is possible to agitate the liquid inside the liquid delivery mechanism in conjunction with the liquid delivery operation.

[0062] 12 and 13, the liquid delivery mechanism (liquid delivery syringe) includes a propeller element 47 at the tip of the drive plunger 44, the propeller element 47 having a radius larger than that of the drive plunger 44, and a bearing 46 that holds the propeller element 47 slidably in the circumferential direction relative to the drive plunger 44. FIG. 13 is a view of the drive plunger 44, the bearing 46, and the propeller element 47 as viewed from the axial direction. With this configuration, the drive plunger 44 moves during the liquid delivery operation, causing the propeller element 47 to rotate, thereby more effectively stirring the liquid inside.

[0063] In this way, when the liquid delivery mechanism has a function of stirring the inside of the mechanism in association with the liquid delivery operation, it is possible to quickly mix the high-concentration reagent and the diluted reagent delivered to the third flow path 43 by attaching the liquid delivery mechanism to the third flow path 43 immediately after the junction 37. Note that the shape of the drive plunger 44 and the shapes of additional parts for stirring the inside of the liquid delivery mechanism are not limited to the above example, and can be selected appropriately by a person skilled in the art as long as they have the effect of promoting mixing of the high-concentration reagent and the diluted reagent.

[0064] In consideration of the sedimentation phenomenon, it is desirable to connect the second flow path 42 (and the third flow path 43) through which the diluted reagent solution is delivered at the confluence 37 so that they are higher than the first flow path 41 through which the high-concentration reagent is delivered. In other words, it is desirable to connect the high-concentration side lower than the low-concentration side. For example, in this embodiment, as a configuration that satisfies the above conditions, the confluence 37 is shaped (so-called T-shaped; see FIG. 4, etc.) in which the first flow path 41 through which the high-concentration reagent is delivered is connected vertically downward, and the second flow path 42 (and the third flow path 43) through which the diluted reagent solution is delivered is connected horizontally above the connection portion of the first flow path 41. This prevents the high-concentration reagent from settling and leaking from the second flow path 42 into the first flow path 41 and the third flow path 43 when the device is not operating (when the reagent preparation unit 106 is not operating).

[0065] Figure 14 is a diagram showing a modified example of the confluence. In Figure 14, the confluence 48 has multiple branch points. By having multiple branch points, when the high-concentration reagent is aspirated (delivered) into the confluence 48, it is simultaneously aspirated from multiple branch points, so that the high-concentration reagent and the diluted reagent are alternately delivered at short intervals, enabling the high-concentration reagent and the diluted reagent to be mixed more quickly. The confluence 48 and each flow path are connected by connectors.

[0066] Fig. 15 shows another modified example of the confluence section. Fig. 15 shows a configuration having a plurality of confluence sections 37 each having a single confluence section. In this case, mixing can be promoted in the same way as in Fig. 14.

[0067] In order to promote mixing in the third flow path 43, the operation of aspirating the high concentration reagent and the operation of discharging it into the third flow path 43 may be performed multiple times in one cycle.

[0068] A second embodiment of the present invention will be described with reference to Fig. 16. The reagent preparation unit 106 shown in Fig. 16 differs from the reagent preparation unit 106 shown in Fig. 2 in that it includes a pressure release branch 49 for releasing pressure in the third flow path 43 (a flow path that closes when the solenoid valve is fully closed). Specifically, in Fig. 16, the reagent preparation unit 106 includes the pressure release branch 49 disposed in the third flow path 43, a fourth flow path 50 for releasing atmospheric pressure that branches off and connects to the pressure release branch 49, and a solenoid valve 51 for releasing the pressure in the fourth flow path 50 for releasing atmospheric pressure to the atmosphere.

[0069] Fig. 17 is a timing chart illustrating the reagent supply operation in the configuration of Fig. 16. In this operation, after the mixed liquid discharge operation in STEP 3 is completed, the electromagnetic valve 51 for releasing atmospheric pressure is opened, thereby making it possible to suppress a pressure rise in the reagent flow path.

[0070] As previously described with reference to FIG. 2 , the high-concentration reagent and diluent are uniformly mixed within the third flow path 43. Therefore, the reagent and diluent may not be sufficiently mixed near the confluence 37 where the high-concentration reagent and diluent meet. Therefore, if the fourth flow path 50 is installed near the confluence 37, an inhomogeneous mixture may move into the fourth flow path 50, potentially causing fluctuations in the concentration of the mixture discharged from the prepared reagent discharge nozzle 25. Therefore, it is desirable to install the fourth flow path near the flow path where the reagent and diluent are sufficiently mixed, i.e., near the solenoid valve 38. In this embodiment, when the reagent preparation unit 106 of FIG. 2 is used, the possibility of the mixture leaking from the prepared reagent discharge nozzle 25 via the flow path can be completely eliminated if the solenoid valve 38 is open for a long period of time.

[0071] A third embodiment of the present invention will be described with reference to Fig. 18. In this embodiment, the reagent preparation unit 106 is configured to deliver prepared reagent to a plurality of dilution tanks 11a and 11b (in other words, a plurality of ISE analysis units).

[0072] FIG. 18 is a diagram illustrating the reagent preparation unit 106 according to this embodiment, along with related components. In the figure, components similar to those in the first embodiment are designated by the same reference numerals, and their description will be omitted. In FIG. 18, a reagent supply branch unit 54 is provided for branching the destination of the reagent in the third flow path 43. The destination of the reagent can be switched between the dilution tanks 11a and 11b by operating the corresponding solenoid valve, and the reagents discharged into each dilution tank 11a and 11b can be analyzed by the respective ISE analysis units (not shown). While FIG. 18 illustrates a single reagent supply branch unit 54 capable of supplying reagent to two dilution tanks 11a and 11b, adding additional reagent supply branch units 54 allows the reagent to be supplied to additional dilution tanks.

[0073] When supplying reagent to multiple dilution tanks 11a, 11b, it is desirable to match the piping resistances in the flow paths from the reagent supply branch 54 to each prepared reagent discharge nozzle 25a, 25b. This is to ensure that the amount of high-concentration reagent leaking from the first flow path 41 at the junction 37 at the end of discharge is constant when the reagent is delivered to systems with different piping resistances. Since there are two dilution tanks, prepared reagent preheaters 12a, 12b are provided, respectively, and two solenoid valves 38a, 38b are provided to control the delivery of the reagent to the dilution tanks 11a, 11b, respectively. However, the other configurations are the same as those shown in FIG. 2 of the first embodiment.

[0074] FIG. 19 is a timing chart illustrating the reagent supply operation of the reagent preparation unit 106 for the multiple dilution tanks 11a and 11b shown in FIG. 18. STEP 1 and STEP 2 are the same as those in FIG. 5. In STEP 3, the solenoid valve 38a is opened and the liquid supply syringe 36 is operated to discharge the mixed solution, thereby discharging the prepared reagent from the prepared reagent discharge nozzle 25a into the dilution tank 11a. After discharge, the liquid supply syringe 36 is operated to suck in a small amount of air from the tip of the prepared reagent discharge nozzle 25a. The solenoid valve 38a remains open until the start of the next reagent supply operation. After the air suction operation is completed, the solenoid valve 38b is opened. The solenoid valves 38a and 38b are closed upon the start of the reagent supply operation to the dilution tank 11b. After the operations of STEP 1 and STEP 2, the liquid supply syringe 36 is operated to discharge the mixed liquid from the prepared reagent discharge nozzle 25b into the dilution tank 11b while the electromagnetic valve 38b is open.

[0075] After dispensing, a small amount of air is sucked from the tip of the prepared reagent dispensing nozzle 25b by performing a suction operation with the liquid supply syringe 36. The solenoid valve 38b remains open until the start of the next reagent supply operation. After the air suction operation is completed, the solenoid valve 38a is opened. Thereafter, the above operation is repeated to repeatedly dispense the mixed solution into the dilution tanks 11a and 11b.

[0076] While the concentration of the internal standard solution in dilution tank 11a is being measured, the concentration of the sample is being measured in dilution tank 11b. While the concentration of the internal standard solution in dilution tank 11b is being measured, the concentration of the sample is being measured in dilution tank 11a. Although Fig. 19 shows an example in which both solenoid valves 38a and 38b are opened during concentration measurement, opening only one of the solenoid valves can be expected to have the effect of suppressing pressure increases in the reagent flow path.

[0077] In FIG. 19 , the solenoid valves 38 a and 38 b remain open until the start of the next reagent supply operation. However, if the pressure in the closed flow path surrounded by the solenoid valves can be released before the start of the next reagent supply operation, dilution of the reagent due to backflow of the mixed solution into the first flow path 41 can be suppressed. Therefore, as shown in FIG. 20 , dilution of the reagent can be prevented by opening the solenoid valves 38 a and 38 b just before the start of the operation for a time sufficient to release the pressure in the closed flow path. The solenoid valves 38 a and 38 b should be open for a time sufficient to release the pressure in the closed flow path, taking into account the volume of the closed flow path (i.e., the length of the flow path that constitutes it multiplied by the cross-sectional area of ​​the flow path piping) and the degree of temperature rise in the analyzer. Furthermore, although the timing for opening the solenoid valves 38 a and 38 b is preferably just before the start of the next reagent supply operation, it is not necessary to open them just before the start of the next reagent supply operation as long as backflow of the mixed solution into the first flow path 41 can be suppressed to a practically acceptable level. In addition, in FIG. 20 as well, the effect of suppressing the pressure rise in the reagent flow path can be expected by simply opening one of the electromagnetic valves.

[0078] <Notes> The analyzer shown in this example is configured to draw a portion of the mixed solution discharged into the dilution tank 11 into the ISE electrode 1 using the shipper nozzle 13 and the shipper syringe 10. Therefore, even if slight volume fluctuations occur due to temperature changes, this does not affect the measurement as long as the reagent concentration does not change.

[0079] This example also describes the effect of an increase in the temperature of the reagent flow path. Depending on the configuration of the device, it is possible that the closed flow path may be cooled by the influence of the ambient temperature, causing a decrease in the pressure in the closed flow path. If the solenoid valve 39 is opened at this time, excess reagent will be supplied into the flow path, causing the concentration of the mixed solution to increase. The configuration shown in this example is also expected to have a similar effect of suppressing concentration fluctuations when affected by a decrease in temperature.

[0080] In the operation of this embodiment, the solenoid valve 38 is open for a longer period of time than it is closed. Considering the lifespan of the solenoid valve and the effect of heat generated by the solenoid valve on measurement data, it is desirable to use a normally open type solenoid valve 38 that closes when powered and opens when powered off.

[0081] It should be noted that the present invention is not limited to the above-described embodiments and includes various modifications. For example, the above-described embodiments have been described in detail to clearly explain the present invention, and it is not necessary to include all of the described configurations. Furthermore, a part of one embodiment can be replaced with a configuration of another embodiment. Furthermore, a configuration of another embodiment can be added to a configuration of one embodiment. Furthermore, a part of the configuration of each embodiment can be deleted.

[0082] 1...ISE electrode, 2...reference electrode, 3...high-concentration reagent bottle, 4...reagent dilution bottle, 5...specimen dilution bottle, 6...reference electrode solution bottle, 7...degassing mechanism, 8...reagent suction nozzle, 9...specimen dilution syringe, 10...sipper syringe, 11...dilution tank, 12...preheater, 13...sipper nozzle, 14...sample probe, 15...sample container, 16...filter, 17...solenoid valve, 18...solenoid valve, 20...solenoid valve, 21...solenoid valve, 22...solenoid valve, 23...pinch valve, 24...specimen dilution solution discharge nozzle, 25...prepared reagent discharge nozzle, 26...first waste liquid nozzle, 27...voltmeter, 28...amplifier, 29...controller, 30...second waste liquid nozzle, 31...solenoid valve, 3 2...solenoid valve, 33...vacuum pump, 34...vacuum bottle, 36...liquid supply syringe, 37...junction, 38...solenoid valve, 39...solenoid valve, 40...solenoid valve, 41...first flow path, 42...second flow path, 43...third flow path, 44...drive plunger, 45...cylindrical part, 46...bearing, 47...propeller part, 48...junction, 49...pressure release branch part, 50...fourth flow path, 51...solenoid valve, 52...second liquid supply syringe, 53...solenoid valve, 54...reagent supply branch part, 100...electrolyte analyzer, 101...sample dispensing part, 102...ISE electrode part, 103...reagent part, 104...reference electrode solution supply part, 105...specimen dilution solution supply part, 106...reagent preparation part, 107...waste liquid mechanism

Claims

1. An analyzer comprising: a high-concentration reagent bottle containing a high-concentration reagent; a reagent dilution bottle containing a reagent dilution liquid for diluting the high-concentration reagent; a first flow path for delivering the high-concentration reagent from the high-concentration reagent bottle; a second flow path for delivering the reagent dilution liquid from the reagent dilution liquid bottle; a junction where the first flow path and the second flow path join; a third flow path for delivering a prepared reagent, which is a mixture of the high-concentration reagent and the reagent dilution liquid, from the junction; a dilution tank containing the prepared reagent; a prepared reagent discharge nozzle for discharging the prepared reagent delivered through the third flow path into the dilution tank; a liquid delivery mechanism for delivering the high-concentration reagent and the reagent dilution liquid to the junction at a predetermined ratio so that the prepared reagent discharged from the prepared reagent discharge nozzle into the dilution tank via the third flow path has a predetermined concentration; and an analysis unit for performing analysis using the prepared reagent contained in the dilution tank, an analytical apparatus comprising: a control unit that controls a valve connected to the third flow path to open for a predetermined time in order to release the pressure in the third flow path after the prepared reagent is discharged from the prepared reagent discharge nozzle into the dilution tank and before the start of analysis of the next prepared reagent in the dilution tank.

2. The analytical device according to claim 1, wherein the valve is a valve provided between the third flow path and the prepared reagent discharge nozzle.

3. An analytical device according to claim 1, wherein the valve is a valve provided between an open end that is open to the atmosphere and the third flow path.

4. An analytical device according to claim 1, characterized in that the control unit controls the liquid delivery mechanism to suck air from the tip of the prepared reagent discharge nozzle after the prepared reagent is discharged from the prepared reagent discharge nozzle into the dilution tank and before the analytical unit analyzes the prepared reagent contained in the dilution tank.

5. An analytical device according to claim 1, wherein the liquid delivery mechanism has a liquid delivery syringe provided in either the first flow path or the second flow path.

6. An analytical device according to claim 1, wherein the liquid delivery mechanism has a liquid delivery syringe arranged on the prepared reagent discharge nozzle side of the third flow path.

7. An analytical device according to claim 1, wherein the liquid delivery mechanism has a liquid delivery syringe arranged on the confluence side of the third flow path, and the liquid delivery syringe has a stirring mechanism that stirs the fluid inside the liquid delivery syringe in conjunction with the liquid delivery operation.

8. An analytical device according to claim 1, characterized in that the confluence is connected to the first flow path from a vertically downward direction, and the second flow path is connected from above the first flow path.

9. An analytical device according to claim 1, wherein the confluence section has a branching structure that branches the high-concentration reagent delivered through the first flow path into at least two, and each of the high-concentration reagents delivered through the branching structure is brought into confluence with the diluted reagent delivered through the first flow path.

10. The analytical device according to claim 1, characterized in that it comprises a plurality of said confluence sections.

11. An analytical apparatus according to claim 1, comprising a plurality of said dilution tanks, and wherein said third flow path is provided with a reagent supply branching section that branches into a plurality of flow paths that deliver said prepared reagent to said plurality of dilution tanks.

12. An analytical device according to any one of claims 1 to 11, characterized in that the high-concentration reagent is a reagent for electrolyte analysis, and the analytical section is equipped with an ion-selective electrode.

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