Sample dilution device, sample dilution method, and chemical analysis system

Abstract

To provide a sample dilution device, a sample dilution method, and a chemical analysis system equipped with the sample dilution device which are capable of highly accurately and easily diluting a sample in quantitative analysis.SOLUTION: Provided are a sample dilution device and a sample dilution method. The sample dilution device comprises a dilution vessel 18, a liquid extraction passage L4 in the vessel, a sample liquid supply passage L1, a common passage L6 connected to the sample liquid passage and the extraction passage, a diluent supply passage L2, a measuring pump 10 for the diluent, a dilution sample liquid passage L3 for supplying the sample liquid and the diluent to the vessel, a valve 16 for switching the passage connected to the common passage between the sample liquid passage and the extraction passage, a discharge passage L5 for the supply liquid from the common passage, a suction pump 12 provided in the discharge passage, and a sample loop 24 for storing a certain amount of the supply liquid, further comprising a valve 14 capable of switching between a passage connected to the discharge passage through or without the common passage and the sample loop and a passage connected to the dilution sample liquid passage through or without the diluent passage and the sample loop.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to a sample dilution device for diluting a liquid sample to a required state when quantitatively analyzing chemical components in the liquid sample, a sample dilution method, and a chemical analysis system equipped with the sample dilution device. [Background technology]

[0002] In highly sensitive analytical methods such as fluorescence analysis, mass analysis, atomic spectrometry (emission, absorption, etc.), liquid chromatography, ion chromatography, and gas chromatography, it is necessary to dilute high concentration (% level) chemical components to low concentration below ppm level in order to quantify chemical components in a liquid sample. For example, Patent Document 1 discloses a method of adjusting the dilution ratio by measuring and mixing a sample liquid and a diluent using a peristaltic pump. Patent Document 2 discloses a method of aspirating a sample liquid and a diluent using a common aspirator, mixing them at the outlet of the aspirator, and diluting them. Furthermore, Patent Document 3 discloses a method of mixing and diluting by introducing and measuring a sample liquid into a tube using a negative pressure suction method using a nebulizer while measuring and sending a diluent using a pump.

[0003] Patent Document 4 discloses a method in which a single pump is used to aspirate diluent from one end of a tube to fill the tube with the diluent, then the other end of the tube is placed in sample liquid and the pump is rotated in reverse to aspirate a specified amount of sample liquid into the tube, and the aspirated sample liquid and the diluent in the tube are discharged from the other end of the tube into a dilution container. Patent Document 5 discloses a method in which a single aspirating and discharging nozzle is used to aspirate a small amount of air, a specified amount of diluent, a small amount of air, and a specified amount of sample liquid in that order, and the sample liquid is discharged from the diluent into a dilution container to dilute the sample liquid.

[0004] Patent Document 6 discloses a method in which a pressure adjusting means draws the sample liquid and the diluent into separate tubes in a reduced pressure state, irradiates each tube with light to detect flow, and after a certain amount of liquid is stored in the tube, the flow path is switched to introduce the stored sample liquid and the diluent into a dilution container. Patent Document 7 discloses a method in which the diluent is filled into a measuring device, discharged into a dilution container by compressed air, and then the sample liquid is filled into another measuring tube, pushed out by compressed air and discharged into a dilution container, thereby diluting. In the second stage of dilution, the primary diluent and the diluent in the dilution container are introduced into another dilution container for dilution. Patent Document 8 discloses an apparatus having a pump for sending the diluent and a plurality of valves for selecting any flow path (tubes with different lengths and inner diameters) and for injecting the sample liquid. With this apparatus, the sample liquid is stored in a tube, the flow path is switched by the valve, the diluent is sent by the pump, and the stored sample liquid and diluent are introduced into the selected flow path, thereby performing mixed dilution. In addition, in a conventional method in which a single low-volume (e.g., 1 μL) microsyringe is used to collect and dilute the sample liquid, the microsyringe is washed several times between the first and second dilution steps. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Japanese Patent Application Publication No. 11-6788 [Patent Document 2] Patent No. 3605818 [Patent Document 3] JP 2012-083188 A [Patent Document 4] JP 2000-146784 A [Patent Document 5] Special Publication No. 8-010214 [Patent Document 6] Patent No. 4150271 [Patent Document 7] JP 2012-220246 A [Patent Document 8] Japanese Patent Application Publication No. 6-308137 Summary of the Invention [Problem to be solved by the invention]

[0006] In the method described in Patent Document 1, the sample liquid and the diluent are measured separately, so high-precision pumps are required for both, and measurement errors are likely to occur. Furthermore, it does not support high-magnification dilution. And in the methods described in Patent Documents 2 and 3, the sample liquid is measured by negative pressure suction while the diluent is delivered, mixed, and diluted, but it is difficult to ensure measurement accuracy. Also, a large amount of diluent is required for high-magnification dilution.

[0007] In the method described in Patent Document 4, the range of dilution ratio is narrow due to the limitation of the capacity of the tube, and the operation is complicated because the sample liquid and the dilution liquid are sucked in by rotating the pump in reverse. In the method described in Patent Document 5, it is difficult to increase the dilution ratio due to the limitation of the capacity of the suction and discharge nozzle. In the method described in Patent Document 6, complex and expensive devices such as a light irradiator, a photodetector, and a pressure regulator are required, and the operation is also complicated. In the method described in Patent Document 7, a measuring device and a measuring tube for measuring the dilution liquid and the sample liquid, respectively, and a large number of switching valves are required, and in the case of multi-stage dilution, it is necessary to increase the number of dilution containers. In addition, in the method described in Patent Document 8, it is necessary to prepare multiple types of tubes, and the range of dilution ratio is also limited.

[0008] In order to realize a highly accurate quantitative analysis in the above-mentioned highly sensitive analytical method, it is desirable to perform a high-magnification dilution of a high-concentration sample, exceeding 100,000 times, easily and quickly with high accuracy. In addition, some types of analytical methods, such as spectroscopic analysis, have limitations on the dynamic range of analytical sensitivity, and it is necessary to perform a wide range of dilution operations from low to high magnifications according to the sample liquids of various concentration ranges. The accuracy of dilution by this dilution operation directly affects the analytical accuracy, and one of the factors that determines the dilution accuracy is the measurement accuracy of the sample liquid and the dilution liquid. Furthermore, although the amount of analytical sample required for most highly sensitive chemical analyses is several mL or less, in the case of a high dilution ratio exceeding 100,000 times, a large amount of dilution liquid, such as more than 100 mL, is required even if a very small amount of microsyringe, such as 1 μL, is used, and in addition, it leads to high costs such as the use of expensive microsyringes, expensive large diluters, and the treatment of large amounts of waste liquid. Furthermore, in order to reduce the amount of dilution liquid required when diluting at a high ratio, multi-stage dilution may be performed. In order to reduce the number of expensive microsyringes used in the first dilution and the second and subsequent dilution steps, the same microsyringe is used for the sample liquid before dilution and the sample liquid after the first stage dilution. However, in order to remove the sample liquid remaining inside the microsyringe, cleaning must be repeated several tens of times, which is both a burden on the operator and requires a large amount of cleaning liquid.

[0009] An object of the present invention is to provide a sample dilution device, a sample dilution method, and a chemical analysis system equipped with a sample dilution device, which are capable of diluting a sample in a quantitative analysis with high accuracy and in a simple manner. [Means for solving the problem]

[0010] The inventors discovered that a quantitative storage flow path capable of measuring and storing an accurate amount can be used not only to measure the amount of the undiluted sample solution but also to measure the amount of the diluted sample solution, thereby enabling sample dilution to be performed easily and with high precision, and thus completed the present invention. In this sample dilution device and sample dilution method, the preparation of the diluted solution can be performed easily and at low cost.

[0011] Specifically, the present invention relates to the following sample dilution devices (1) to (5). (1) A container to which a sample liquid to be diluted and a diluent are supplied, an extraction flow path for extracting a mixed liquid from the container, a sample liquid flow path for supplying the sample liquid, a common flow path connecting the sample liquid flow path and the extraction flow path, a diluent flow path for supplying the diluent, a liquid delivery means provided in the diluent flow path for delivering a predetermined amount of diluent, a diluted sample liquid flow path for supplying the sample liquid and the diluent to the container, a first flow path switch for switching a flow path connected to the common flow path between the sample liquid flow path and the extraction flow path, and a discharge flow path for discharging a liquid supplied from the common flow path. a flow path that connects the dilution liquid flow path to the diluted sample liquid flow path via the fixed quantity storage flow path, a discharge means provided in the discharge flow path, a fixed quantity storage flow path that temporarily stores a fixed amount of the liquid supplied, a flow path 1 that connects from the common flow path to the discharge flow path via the fixed quantity storage flow path, a flow path 2 that connects from the dilution liquid flow path to the diluted sample liquid flow path via the fixed quantity storage flow path, a flow path 3 that connects from the common flow path to the discharge flow path without passing through the fixed quantity storage flow path, and a flow path 4 that connects from the dilution liquid flow path to the diluted sample liquid flow path without passing through the fixed quantity storage flow path. (2) A sample dilution device as described in (1) above, comprising a reactor, a raw material liquid supply flow path for supplying a raw material liquid to the reactor, and a product supply flow path for supplying a liquid containing a product produced in the reactor to the sample liquid flow path. (3) A sample dilution device as described in (1) above, comprising a plurality of sample liquid flow paths, a first flow path switch for switching the flow paths connected to the common flow path between each sample liquid flow path and an extraction flow path, and further comprising a plurality of second flow path switchers connected in series so that a flow path supplied from the diluent flow path and which may or may not pass through the fixed quantity storage flow path and a flow path supplied from the common flow path and which may or may not pass through the fixed quantity storage flow path are in parallel, and the most upstream second flow path switch is connected to the diluent flow path and the common flow path, and the most downstream second flow path switch is connected to the diluted sample liquid flow path and the discharge flow path. (4) Step 1 of connecting the sample liquid flow path to the common flow path by the first flow path switch and to flow path 1 by the second flow path switch, and storing the sample liquid supplied from the sample liquid flow path in the fixed quantity storage flow path by the discharge means; Step 2 of switching the second flow path switch to flow path 2 and supplying a predetermined amount of diluent by the liquid sending means to supply the sample liquid stored in the fixed quantity storage flow path and the diluent from the diluted sample liquid flow path to the container; Step 3 of connecting the extraction flow path to the common flow path by the first flow path switch and switching the second flow path switch to connect to flow path 1, and storing the mixed liquid in the container in the fixed quantity storage flow path by the discharge means; Step 4 of connecting the extraction flow path to the common flow path by the first flow path switch and to flow path 2 by the second flow path switch; a step 5 of switching the second flow path switch to connect to flow path 4 and supplying a predetermined amount of diluent from the diluted sample liquid flow path to the container by the liquid delivery means; a step 6 of connecting the extraction flow path to the common flow path by the first flow path switch and switching the second flow path switch to connect to flow path 3 and discharging all of the diluent from the container by the discharge means; and a step 7 of switching the second flow path switch to connect to flow path 2 and supplying a predetermined amount of diluent by the liquid delivery means to supply the mixed liquid and diluent stored in the fixed quantity storage flow path from the diluted sample liquid flow path to the container, in the order of steps 1 to 7. (5) The sample dilution device according to (4) above, further comprising a function for repeating steps 3-7 one or more times after steps 1-7. The present invention also relates to the following sample dilution methods (6)-(7). (6) A method for diluting a sample liquid using the sample dilution device described in (1) or (2), comprising the steps of: (1) connecting the sample liquid flow path to the common flow path by the first flow path switch, and switching the flow path to flow path 1 by the second flow path switch, supplying sample liquid from the sample liquid flow path, and storing the sample liquid in the fixed-quantity storage flow path by the discharge means; (2) switching the second flow path switch to flow path 2, and supplying a predetermined amount of diluent by the liquid delivery means, and supplying the sample liquid stored in the fixed-quantity storage flow path and the diluent from the diluted sample liquid flow path to the container; (3) connecting the extraction flow path to the common flow path by the first flow path switch, and switching the second flow path switch to connect to flow path 1, and storing the mixed liquid in the container in the fixed-quantity storage flow path by the discharge means; a step 5 of connecting the first flow path to the common flow path by the first flow path switch and switching the second flow path switch to connect to flow path 3 and discharging the mixed liquid in the container by the discharge means; a step 6 of connecting the first flow path to the common flow path by the first flow path switch and switching the second flow path switch to connect to flow path 3 and discharging the entire amount of diluent in the container by the discharge means; and a step 7 of switching the second flow path switch to connect to flow path 2 and supplying a predetermined amount of diluent by the liquid sending means to supply the mixed liquid and diluent stored in the fixed amount storage flow path from the diluted sample liquid flow path to the container in the order of steps 1 to 7. (7) The sample dilution method according to (6), wherein, after steps 1-7, steps 3-7 are repeated one or more times.

[0012] The present invention also relates to the following chemical analysis systems (8)-(16). (8) A chemical analysis system comprising a sample dilution device according to any one of (1) to (3) above and a chemical analysis device that analyzes the mixed liquid in the container, wherein the container is used as a measurement cell of the chemical analysis device. (9) A chemical analysis system comprising a sample dilution device according to any one of (1) to (3) and a chemical analysis device for analyzing the mixed liquid in the container, the chemical analysis system comprising a first discharge means for discharging the mixed liquid in the container, a supply means for supplying the mixed liquid discharged by the first discharge means to a measurement cell of the chemical analysis device, and a second discharge means for discharging the mixed liquid supplied by the supply means from the measurement cell. (10) A chemical analysis system comprising a sample dilution device according to any one of (1) to (3) and a chemical analysis apparatus for analyzing the mixed liquid in the container, the chemical analysis system further comprising a discharge means for discharging the mixed liquid in the container and a supply means for supplying the mixed liquid discharged by the discharge means to the chemical analysis apparatus. (11) A chemical analysis system comprising the sample dilution device according to (4) or (5) and a chemical analysis device that analyzes the mixed liquid in the container, wherein the container is used as a measurement cell of the chemical analysis device, and steps 1-7 are performed in order to continuously dilute and measure the sample liquid. (12) A chemical analysis system comprising the sample dilution device according to (4) or (5) and a chemical analysis device for analyzing the mixed liquid in the container, the chemical analysis system including a first discharge means for discharging the mixed liquid in the container, a supply means for supplying the mixed liquid discharged by the first discharge means to a measurement cell of the chemical analysis device, and a second discharge means for discharging the mixed liquid supplied by the supply means from the measurement cell, the chemical analysis system diluting the sample liquid by executing steps 1-7 in order, and simultaneously or continuously diluting and measuring the sample liquid by the first discharge means, the supply means, and the second discharge means. (13) A chemical analysis system comprising the sample dilution device according to (4) or (5) and a chemical analysis device for analyzing the mixed liquid in the container, the chemical analysis system including a discharge means for discharging the mixed liquid in the container and a supply means for supplying the mixed liquid discharged by the discharge means to the chemical analysis device, the chemical analysis system diluting the sample liquid by executing steps 1-7 in order, and diluting and measuring the sample liquid simultaneously or consecutively by the discharge means and the supply means. (14) The chemical analysis system according to (11) above, wherein the dilution and measurement of the sample liquid are performed online. (15) The chemical analysis system according to (12) above, wherein the dilution and measurement of the sample liquid are performed online. (16) The chemical analysis system according to (13) above, wherein the dilution and measurement of the sample liquid are performed online. Effect of the Invention

[0013] According to the present invention, it is possible to provide a sample dilution device, a sample dilution method, and a chemical analysis system equipped with a sample dilution device, which are capable of diluting a sample in a quantitative analysis easily and with high accuracy. [Brief description of the drawings]

[0014] [Figure 1] FIG. 1 is a diagram showing the configuration of a sample dilution device (first embodiment). [Diagram 2] 11 is a diagram showing a flow path switching state of an injection valve and a three-way valve. FIG. [Diagram 3] This is a diagram showing the liquid route of the sample dilution device. (Operation 1) [Figure 4] This is a diagram showing the liquid route of the sample dilution device (operation 2). [Diagram 5] This is a diagram showing the liquid route of the sample dilution device (operation 3). [Figure 6] This is a diagram showing the liquid route of the sample dilution device (operation 4, operation 6). [Figure 7] This is a diagram showing the liquid route of the sample dilution device (Operation 5). [Figure 8] This is a diagram showing the liquid route of the sample dilution device (operation 7). [Figure 9] FIG. 13 is a diagram showing the configuration of a sample dilution device according to another embodiment (Embodiment 2). [Figure 10] FIG. 13 is a diagram showing the configuration of a sample dilution device according to another embodiment (Embodiment 3). [Figure 11] FIG. 13 is a diagram showing the flow path switching state of the injection valve and the four-way valve (Embodiment 3). [Figure 12] 13 is a diagram showing the configuration of a chemical analysis system equipped with a sample dilution device (Embodiment 4). [Figure 13] 13 is a diagram showing the configuration of a chemical analysis system equipped with a sample dilution device (Embodiment 5). [Figure 14] 13 is a diagram showing the configuration of a chemical analysis system equipped with a sample dilution device (Embodiment 6). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0015] (Embodiment 1) A configuration example of the sample dilution device of this embodiment is shown in Fig. 1. This sample dilution device 1 is mainly composed of a metering pump 10, a suction pump 12, a 6-port two-way injection valve (hereinafter referred to as an injection valve) 14 and a three-way valve 16 serving as a flow path switch, a dilution container 18 in which a mixture of a sample liquid and a dilution liquid is stored, and the like. Also, a sample liquid container 20 in which a sample liquid to be diluted is stored, a dilution liquid container 22 in which a dilution liquid is stored, and the like are arranged. As flow paths (tubes, etc.) for the sample liquid and the dilution liquid, etc., the device includes a sample liquid flow path L1 for supplying the sample liquid to be diluted, a dilution liquid flow path L2 for supplying a predetermined amount of dilution liquid by the metering pump 10, a diluted sample liquid flow path L3 connected to the dilution liquid flow path L2, an extraction flow path L4 for extracting the liquid in the dilution container 18, a common flow path L6 connected to the sample liquid flow path L1 and the extraction flow path L4, and an exhaust flow path L5 connected to the common flow path L6 and for discharging the liquid supplied from the common flow path L6 by the suction pump 12, and the like. In the drawings, the same reference numerals denote the same or corresponding parts. In the present specification, when a numerical range is given, the upper and lower limits are included.

[0016] A sample loop 24 is connected to the injection valve 14 as a fixed-volume storage flow path that temporarily stores a certain amount of the supplied liquid. The fixed-volume storage flow path is not limited to a loop, and may be a straight pipe of a fixed volume, as long as it can measure and store an accurate amount. The three-way valve 16 is an example of a flow path switch that switches the flow path connected to the common flow path L6 between the sample liquid flow path L1 and the extraction flow path L4. As another example, instead of the three-way valve 16, an opening and closing valve may be provided in each of the flow paths L1 and L4. 2 shows the flow path switching states of the injection valve 14 and the three-way valve 16. The injection valve 14 has six ports, ports P1-P6, and can change the flow path between two modes, mode A shown in (A) and mode B shown in (B). The three-way valve 16 can change the flow path between two modes, mode C shown in (C) and mode D shown in (D).

[0017] Port P1 of the injection valve 14 is connected to the diluent flow path L2, and port P5 is connected to a common flow path L6. Each of the ports P1 and P5 serves as an inlet for the liquid supplied from each of the flow paths L2 and L6. Port P2 is connected to the diluted sample liquid flow path L3, and port P4 is connected to the discharge flow path L5. Each of the ports P2 and P4 serves as an outlet for the liquid supplied to each of the flow paths L3 and L5.

[0018] When the injection valve 14 is in mode A, a flow path is formed in which ports P1 and P2 are connected, and ports P5 and P6 are connected, and ports P3 and P4 are connected via the sample loop 24. In this mode A, the liquid supplied to port P1 is supplied from port P2 to the diluted sample liquid flow path L3 without passing through the sample loop 24. Moreover, the liquid supplied to port P5 is supplied from port P4 to the discharge flow path L5 via the sample loop 24.

[0019] When the injection valve 14 is in mode B, the port P1 and the port P6 are connected, and a flow path is formed in which the port P3 and the port P2 are connected via the sample loop 24, and a flow path is formed in which the port P5 and the port P4 are connected. In this mode B, the liquid supplied to the port P1 is supplied to the diluted sample liquid flow path L3 from the port P2 via the sample loop 24. The liquid supplied to the port P5 is supplied to the discharge flow path L5 from the port P4 without passing through the sample loop 24. In addition, the three-way valve 16 is capable of switching the flow paths by connecting the sample liquid flow path L1 to the common flow path L6 in mode C, and connecting the extraction flow path L4 to the common flow path L6 in mode D. Note that, instead of using the three-way valve 16, opening and closing valves may be provided in the sample liquid flow path L1 and the extraction flow path L4, respectively, to switch between the respective flow paths, but using the three-way valve 16 is preferable because it reduces the number of members and provides a simple configuration.

[0020] By switching between the three-way valve 16 and the injection valve 14, the following routes are formed, for example: route 1 connects the sample liquid flow path L1 to the discharge flow path L5 via the common flow path L6 and the sample loop 24 when the injection valve 14 is in mode A and the three-way valve 16 is in mode C; route 2 connects the diluent flow path L2 to the diluted sample liquid flow path L3 via the sample loop 24 when the injection valve 14 is in mode B, regardless of the mode of the three-way valve 16; route 3 connects the extraction flow path L4 to the discharge flow path L5 via the common flow path L6 and the sample loop 24 when the injection valve 14 is in mode A and the three-way valve 16 is in mode D; and route 4 connects the extraction flow path L4 to the common flow path L6 and then to the discharge flow path L5 without passing through the sample loop 24 when the injection valve 14 is in mode B and the three-way valve 16 is in mode D. When the injection valve 14 is in mode A, regardless of the mode of the three-way valve 16, there is a route 5 that connects the diluent flow path L2 to the diluted sample liquid flow path L3 without passing through the sample loop 24.

[0021] FIG. 3-7 is a diagram for explaining each route, and for ease of understanding, each route is shown in bold. In route 1 (FIG. 3), the sample liquid in the sample liquid container 20 is supplied by the suction pump 12 from the sample liquid flow path L1 through the common flow path L6 and the sample loop 24 to the discharge flow path L5, and a part of it is discharged as drain water. A certain amount of the sample liquid is temporarily stored in the sample loop 24. Various types of sample liquid can be used for the analysis. In particular, the use of polymer or stainless steel valves, sample loops, connecting tubes, etc. is preferable because it prevents contamination and residue compared to materials (glass, ruby, sapphire) that are prone to contamination and residue, or pumps having such structures (syringe type, plunger type). In route 2 (FIG. 4), the diluent (for example, water such as ultrapure water, or an organic solvent such as an acid, an alkali, methanol, acetonitrile, or toluene) in the diluent container 22 is supplied by the metering pump 10 from the diluent flow path L2 to the diluted sample liquid flow path L3 via the sample loop 24, and is stored in the dilution container 18. When a sample liquid or the like is stored in the sample loop 24, the sample loop 24 serves to send the sample liquid or the like to the dilution container 18. The inside of the sample loop 24 can also be washed with the diluent.

[0022] In route 3 (FIG. 5), the liquid in the dilution container 18 is supplied by the suction pump 12 from the extraction flow path L4 to the discharge flow path L5 via the common flow path L6 and the sample loop 24, and a part of the liquid is discharged as drain water. At this time, a certain amount of the liquid in the dilution container 18 is temporarily stored in the sample loop 24. In route 4 (FIG. 6), the liquid in the dilution container 18 is supplied from the extraction flow path L4 to the discharge flow path L5 via the common flow path L6 without passing through the sample loop 24, and is discharged as drain water. In this route, all of the liquid in the dilution container 18 can be discharged. In route 5 (FIG. 7), the diluent in the diluent container 22 is supplied by the metering pump 10 from the diluent flow path L2 to the diluted sample liquid flow path L3 without passing through the sample loop 24, and the diluent is stored in the diluent container 18. To ensure accuracy, the metering pump 10 for the diluent is preferably a pump that can measure a constant flow rate or a volume. For example, the former includes a plunger pump, a peristaltic pump, and a diaphragm pump, which are pumps that can continuously deliver liquid, and the latter (pumps that can measure volume) include a syringe pump and a metering tube.

[0023] Next, the procedure of the multi-stage dilution operation will be explained using, for example, Table 1 and Figures 3-8. [Table 1]

[0024] First, in operation 1, the injection valve 14 and the three-way valve 16 are set to route 1, and the suction pump 12 is operated to suck the sample liquid in the sample liquid container 20 into the sample loop 24 of the injection valve 14 (FIG. 3). Next, in operation 2, the injection valve 14 is switched to route 2, and the diluent in the diluent container 22 is accurately measured using the metering pump 10 and introduced into the sample loop 24. The three-way valve 16 may be in either mode C or mode D. The sample liquid in the sample loop 24 is pushed out in its entirety by the diluent and supplied to the diluent container 18. A mixture of the sample liquid and the diluent is stored in the diluent container 18, and a primary diluent can be obtained (FIG. 4). This primary diluent is a mixture of an accurate amount of diluent measured by the metering pump 10 and the sample liquid stored in the sample loop 24 of a fixed volume, and is therefore a highly accurate diluted sample liquid. In order to improve the mixing efficiency, a stirrer (not shown) may be provided to stir the mixed liquid in the dilution container 18. For example, stirring may be performed by inserting a stirrer or stirring rod into the dilution container 18, or by introducing a gas such as air. By stirring the mixed liquid, a uniform diluted sample liquid is obtained.

[0025] Next, in operation 3, the three-way valve 16 is switched to the extraction flow path L4 side to set route 3. Then, the suction pump 12 causes the primary diluent in the dilution container 18 to accumulate in the sample loop 24 (FIG. 5). This primary diluent is called the primary diluted sample liquid. Note that in this operation, the sample liquid remaining in the common flow path L6 in operation 1 also flows into the sample loop 24, but by increasing the inflow rate of the primary diluent in the dilution container 18, the sample liquid remaining in the common flow path L6 is washed away, so there is no effect on the accuracy of the primary diluent in the sample loop 24. Next, the primary diluent is discharged from the dilution container 18 and the inside of the dilution container 18 is washed. First, as an operation 4, the injection valve 14 is switched to set the route 4. Here, the primary diluent remaining in the dilution container 18 is sucked by the suction pump 12, and almost the entire amount is discharged (FIG. 6). Then, as an operation 5, the injection valve 14 is switched to set the route 5, and the inside of the dilution container 18 is washed. Note that the three-way valve 16 may be in mode C, but it is preferable to continue in mode D from the viewpoint of preventing contamination with the sample liquid. Washing is performed by supplying a fixed amount of diluent (the same amount as the volume of the primary diluent stored in the dilution container 18) to the dilution container 18 by the metering pump 10 (FIG. 7), and then, as an operation 6, the injection valve 14 is switched to set the route 4, and the primary diluent and washing liquid remaining in the dilution container 18 are discharged by the suction pump 12 (FIG. 6). Note that the above-mentioned operations 4-5 may be repeated in order to suppress the primary diluent from remaining in the dilution container 18. As another means for discharging the primary diluent and cleaning liquid from the dilution container 18, a valve (not shown) may be provided at the bottom of the dilution container 18 and the primary diluent and cleaning liquid may be discharged by opening the valve. This is common to the other embodiments.

[0026] Next, in operation 7, in order to prepare a secondary dilution liquid, the primary diluted sample liquid (operation 3) stored in the sample loop 24 is measured with the dilution liquid by the metering pump 10 and introduced into the dilution container 18 to dilute it in the same manner as in the above-mentioned primary dilution method, thereby performing a second-stage dilution (FIG. 8). That is, the primary diluted sample liquid in the sample loop 24 is pushed out in its entirety by the dilution liquid and supplied to the dilution container 18. The third and subsequent stages of dilution can be performed by repeating this second-stage operation (operations 3-7). This multi-stage dilution is performed by accurately measuring the sample liquid or the sample liquid after dilution in the entire amount of the fixed-volume sample loop 24, and the dilution liquid is accurately measured by the highly accurate metering pump 10 and introduced into the sample loop 24, so that a certain amount of the sample liquid or the primary diluted sample liquid, etc. is introduced into the dilution container 18 while being washed away by the dilution liquid, and mixed therein. Thus, according to this embodiment, the sample liquid and the primary diluent can be accurately measured using the same sample loop 24, and the primary diluent and the secondary diluent can be stored in the same dilution container 18. This means that there is no need for measuring tubes or storage containers for each liquid, and sample dilution can be performed easily and with high precision.

[0027] In addition, the primary dilution liquid and the secondary dilution liquid in the dilution container 18 are discharged by the operation of the suction pump 12 and the introduction and washing of the dilution liquid, and no residual liquid remains. Furthermore, the dilution ratio can be adjusted over a wide range by adjusting the amount of dilution liquid and performing multi-stage dilution. Therefore, a high-precision metering pump for the sample liquid is not required, and it is possible to perform multi-stage dilution of the sample liquid with high precision over a wide range of high ratios without adding additional equipment. The metering pump can be freely selected from plunger pumps, syringe pumps, diaphragm pumps, etc. according to the required dilution precision. In addition, the components, solvents, valves, containers, etc. of the sample liquid can be freely selected as long as they satisfy the above dilution principle. Furthermore, the sample liquid can be automatically diluted by controlling the operation of the metering pump 10, suction pump 12, injection valve 14, three-way valve 16, etc. by the control device 30 (FIG. 1) (for example, it may be programmed in advance). In addition, online multi-stage dilution chemical analysis is also possible by connecting this sample dilution device to a chemical analysis device (e.g., fluorescence analysis, mass analysis, atomic spectrum analysis (emission, absorption, etc.), liquid chromatography, ion chromatography, gas chromatography, etc.). This is also common to the other embodiments.

[0028] (Embodiment 2) According to the sample dilution device of this embodiment, not only sample liquid in a container but also reaction liquid flowing in a tube or pipe, such as in an online chemical reaction, can be collected, diluted, and analyzed by the above dilution method. An example of the configuration of the sample dilution device in this case is shown in Fig. 9. This sample dilution device 3 differs from the sample dilution device 1 in Fig. 1 in that a reaction product obtained by reacting raw materials is supplied to the sample liquid flow path L1 as the sample liquid, but other configurations are the same as those of the sample dilution device 1 in Fig. 1, so a description of the common parts will be omitted. The raw material liquids stored in the two types of raw material liquid containers 31 and 33 are introduced into a reactor 35 containing a catalyst or the like and reacted to obtain a product. The product is stored in a product container 39 from a product flow path L7 as a liquid containing the product, and the product is introduced into a sample liquid flow path L1 by switching a switching valve (such as a three-way valve) 37 provided in the product flow path L7. The liquid containing the product is then diluted by a dilution operation similar to that of the first embodiment. Note that, instead of the switching valve 37, an opening and closing valve may be provided in each flow path L1 and L7, or the product flow path L7 and the sample liquid flow path L1 may be used together. In addition, the reactor 35 can be used simply as a mixer to mix and dilute a plurality of types of sample liquid, or one or three or more types of raw material liquid may be used. For example, when two types of raw material liquid are used, there is a reaction in which ethyldimethyl-azapentacyclononadeca-hexaenedione is synthesized from a solution of dimethylanthracene dissolved in acetonitrile and a solution of N-ethylmaleimide. In this manner, also in this embodiment, the reaction liquid is aspirated and collected according to the dilution principle described above, making it possible to carry out the above-mentioned online multi-stage dilution.

[0029] (Embodiment 3) An example of the configuration of a sample dilution device according to another embodiment is shown in Fig. 10. An example of valve switching of this device is shown in Fig. 11. Figs. 11(A) and (B) show an example of valve switching of injection valve 14a, Figs. 11(C) and (D) show an example of valve switching of injection valve 14b, and Figs. 11(E)-(G) show an example of valve switching when a four-way valve is used instead of a three-way valve. This sample dilution device 4 differs from the sample dilution device 1 in Fig. 1 mainly in that it is provided with two injection valves 14a and 14b, but other configurations are similar to those of the sample dilution device 1 in Fig. 1, so a description of the common parts will be omitted.

[0030] This device is equipped with two sample liquid containers 20a, 20b and two injection valves 14a, 14b, and each of the injection valves 14a, 14b having a sample loop 24a, 24b is connected in series by flow paths L8, L9. Specifically, the port P2 of the injection valve 14a is connected to the port P1 of the injection valve 14b by the flow path L8, and the port P4 of the injection valve 14a is connected to the port P5 of the injection valve 14b by the flow path L9. In addition, the diluent flow path L2 is connected to the port P1 of the injection valve 14a, the common flow path L6 is connected to the port P5 of the injection valve 14a, the diluted sample flow path L3 is connected to the port P2 of the injection valve 14b, and the discharge flow path L5 is connected to the port P4 of the injection valve 14b. When sample loops of different volumes (capacities) are used, the injection valve can be switched to select a sample loop according to the required dilution ratio, and the sample liquid can be introduced into the selected sample loop for dilution. This allows the adjustment range of the dilution ratio to be expanded, and the amount of sample liquid for the same dilution ratio to be changed. In addition, by storing different sample liquids in the two sample liquid containers 20a and 20b, different samples can be mixed and diluted.

[0031] As an example, Table 2 shows an operation example when the dilution rate of the sample liquid is decreased. [Table 2]

[0032] For example, when the sample loops 24a and 24b have different capacities, the dilution ratio can be reduced by conducting a dilution operation by introducing the sample liquid into the large-capacity sample loop 24a instead of the small-capacity sample loop 24b. In operation 1, the sample liquid in the sample liquid container 20a is sucked from the sample liquid flow path L1a into the sample loop 24a of one of the injection valves 14a. At this time, the sample liquid flows from the sample loop 24a to the other injection valve 14b, but is discharged from the discharge flow path L5 without passing through the sample loop 24b. In operation 2, the diluent in the diluent container 22 is introduced into the sample loop 24a, and is supplied to the diluted sample liquid flow path L3 from the other injection valve 14b without passing through the sample loop 24b, and is stored in the dilution container 18. In operation 3, the suction pump 12 causes the primary diluent in the dilution container 18 to be stored in the sample loop 24a. In operation 4, the suction pump 12 sucks the primary diluent remaining in the dilution container 18, and almost the entire amount is discharged. In operation 5, the metering pump 10 supplies a certain amount of diluent (washing liquid) to the dilution container 18. In operation 6, the suction pump 12 discharges the primary diluent and washing liquid remaining in the dilution container 18. In operation 7, the primary diluted sample liquid in the sample loop 24a is pushed out entirely by the diluent and supplied to the dilution container 18. The third and subsequent dilutions can be performed by repeating the second-stage operations (operations 3-7).

[0033] In addition, it is possible to increase the amount of sample and decrease the dilution ratio by introducing the same sample liquid into the two sample loops 24a and 24b and performing a dilution operation. An example of this operation is shown in Table 3. [Table 3]

[0034] In operation 1, the sample liquid in the sample liquid container 20a is sucked from the sample liquid flow path L1a into the sample loop 24a of the injection valve 14a. At this time, the sample liquid flows from the sample loop 24a to the sample loop 24b of the other injection valve 14b, and is discharged from the discharge flow path L5. Therefore, the sample liquid is stored in the two sample loops 24a and 24b. In operation 2, the diluent in the diluent container 22 is introduced into the two sample loops 24a and 24b, supplied to the diluted sample liquid flow path L3, and stored in the dilution container 18. In operation 3, the suction pump 12 causes the primary diluent in the dilution container 18 to be stored in the two sample loops 24a and 24b. In operation 4, the suction pump 12 sucks the primary diluent remaining in the dilution container 18, and almost the entire amount is discharged. In operation 5, the metering pump 10 supplies a certain amount of diluent (cleaning liquid) to the dilution container 18. In operation 6, the suction pump 12 discharges the primary diluent and washing solution remaining in the dilution container 18. In operation 7, the primary diluted sample solution in the two sample loops 24a, 24b is pushed out entirely by the diluent and supplied to the dilution container 18. The third and subsequent dilutions can be performed by repeating the second-stage operations (operations 3-7).

[0035] Furthermore, by introducing different sample liquids into the two sample loops and diluting each, it is possible to mix and dilute two types of sample liquid. An example of this operation is shown in Table 4. [Table 4]

[0036] In operation 1, the sample liquid in one sample liquid container 20a is sucked from the sample liquid flow path L1a into the sample loop 24a of the injection valve 14a. In operation 2, the sample liquid in the other sample liquid container 20b is sucked from the sample liquid flow path L1b into the sample loop 24b of the injection valve 14b. In operation 3, the diluent in the diluent container 22 is introduced into the two sample loops 24a and 24b, supplied to the diluted sample liquid flow path L3, and stored in the dilution container 18. In operation 4, the suction pump 12 causes the primary diluent in the dilution container 18 to be stored in the sample loop 24a. In operation 5, the suction pump 12 sucks the primary diluent remaining in the dilution container 18, and almost the entire amount is discharged. In operation 6, the metering pump 10 supplies a certain amount of diluent (washing liquid) to the dilution container 18. In operation 7, the suction pump 12 discharges the primary diluent and washing liquid remaining in the dilution container 18. In operation 8, the first diluted sample liquid in the sample loop 24a is pushed out entirely by the dilution liquid and supplied to the dilution container 18. The third and subsequent dilution steps can be performed by repeating the second step operation (operations 4-8). In addition, the sample loops 24a and 24b can be selected individually or in combination for each dilution step. This combination allows for more precise dilution ratios and more diverse mixed dilutions of sample liquids. In addition, by further installing sample liquid containers 20a and 20b and injection valves 14a and 14b, the range of dilution ratios and mixed dilutions can be further increased or made more precise.

[0037] (Embodiment 4) FIG. 12 shows an example of a chemical analysis system 6 constructed by a sample dilution device 1 and a chemical analysis device 5. According to this system, the dilution container 18 of the sample dilution device 1 is installed in the chemical analysis device 5 as a measurement cell, and the primary dilution solution and the secondary dilution solution obtained by the dilution operation similar to that of the first embodiment can be directly measured from the dilution container 18, and the chemical components can be detected. The chemical analysis device 5 can be used for fluorescence analysis, absorption analysis, Raman spectroscopy, nuclear magnetic resonance analysis, etc., but any type is acceptable as long as it can detect the chemical components in the measurement cell. In addition, the dilution container 18 can be used both for storage and measurement, and the dilution operation and the measurement operation can be performed continuously to speed up the process and shorten the analysis time. The dilution operation and the measurement can be performed automatically by the control device 30, or can be performed online.

[0038] (Embodiment 5) Fig. 13 shows an example of a chemical analysis system 7 constructed by a sample dilution apparatus 1 and a chemical analysis apparatus 5, which is different from the system shown in Fig. 12. This system differs from the system shown in Fig. 12 in that a measurement cell is provided in addition to the dilution container 18, but the rest of the configuration is the same as the chemical analysis system shown in Fig. 12. Table 5 shows an example of the procedure for diluting multiple sample solutions in two steps and sequentially performing three-dimensional fluorescence analysis. [Table 5]

[0039] The two-stage dilution refers to a dilution operation to obtain a secondary dilution liquid. The first sample liquid (SA) is subjected to the dilution operation 1-7 similar to that of the first embodiment, and the obtained diluted sample liquid (secondary dilution liquid) is introduced into the measurement cell 40 installed in the chemical analysis device 5 from the flow path L10 using the pump 41 in operation 8, and measurement is performed. At the same time as this measurement, the next sample liquid (SB) is prepared. That is, in operations 8a-8d, two-stage dilution of the next sample liquid (SB) is performed in parallel with the measurement of the sample liquid (SA). Specifically, after discharging the current diluted sample liquid (SA) in the dilution container 18 and cleaning the dilution container 18 and each flow path, two-stage dilution of the next sample liquid (SB) is performed and stored in the dilution container 18. Thereafter, in operations 9-10, the diluted sample liquid (SA) for which measurement has been completed is discharged from the measurement cell 40 using the pump 43 to the flow path L11, and the next diluted sample liquid (SB) is introduced from the dilution container 18 to the measurement cell 40 and measurement is performed. By repeating these operations for subsequent sample liquids, the time required for multi-stage dilution analysis of multiple sample liquids can be shortened and the analysis can be carried out quickly. By preparing the next sample liquid (the dilution operation in embodiment 1) during measurement, the dilution operation and measurement of the next sample liquid can be carried out simultaneously and continuously. This dilution operation and measurement can be carried out automatically by the control device 30, or can be carried out online.

[0040] (Embodiment 6) FIG. 14 shows an example of a chemical analysis system 8 constructed by a sample dilution device 1 and a chemical analysis device 5, which is different from that shown in FIG. 12. In this system, the diluted sample liquid obtained by the dilution operation similar to that of the first embodiment and stored in the dilution container 18 is directly introduced into the chemical analysis device 5 from the flow path L10 by the pump 41 without using a measurement cell, and is measured. Examples of this analysis device include a mass spectrometer such as an ICP-MS, an atomic absorption spectrometer, an ICP emission spectrometer, and a spectroscopic detector such as a flow cell type absorption or fluorescence detector. In this system, when the diluted sample liquid to be measured is introduced into the dilution container 18, it is continuously measured in a flow format, so that the system has a simple configuration and enables rapid analysis. In addition, the dilution operation and measurement can be performed simultaneously. And, the dilution operation and measurement can be performed automatically by the control device 30, or can be performed online. In addition, these embodiments can be implemented in appropriate combinations.

[0041] An example of the production method of the present invention will be described below using examples, but the present invention is not limited to these examples. Note that % for concentration indicates % by mass. EXAMPLES

[0042] Example 1 To prepare a low-concentration analytical sample solution for high-sensitivity fluorescence analysis of amino acids, two-stage high-magnification dilution was performed and the dilution accuracy was evaluated. The dilution device used was shown in Figure 1. The device consisted of a Veritas slip tube-type suction pump (MINIPULS3, Gilson), a plunger-type metering pump (G1312A, HP), a stainless steel injection valve (6-port two-way injection valve, G1316A, HP) connected to a 10 μL stainless steel sample loop, a PEEK three-way valve (three-way switching valve, C2, VICI), and a dilution container, a glass bottle with a lid, and each was connected with a fluororesin tube (outer diameter 1 / 16 inch) as follows:

[0043] A tube was connected between the sample liquid container 20, a glass bottle containing the sample liquid, and the three-way valve 16, and a tube was connected from the valve outlet to the injection valve 14. This connection port was connected to the sample loop 24, and its outlet was connected to the suction pump 12, with the pump outlet serving as the discharge port. Next, a diluent container 22, a glass bottle containing the diluent, was connected to the metering pump 10, its outlet was connected to the injection valve 14, and it was connected to the sample loop 24, and a tube was inserted from the outlet into the lid and into the dilution container 18 with a volume of 5 mL. Another tube was installed in contact with the bottom surface of the dilution container 18 by penetrating the lid, and the other end of this tube was connected to the three-way valve 16.

[0044] The dilution method of the present invention was evaluated as follows. A 2500 ppm tryptophan aqueous solution (tryptophan reagent (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) dissolved in ultrapure water) was used as the sample solution, and ultrapure water was used as the diluent. The dilution procedure was a two-step dilution according to Table 1. In the first dilution step, based on the operation 1, the three-way valve 16 was switched to mode C to connect the sample liquid container 20 and the injection valve 14, and the injection valve 14 was switched to mode A to connect to the sample loop 24, after which the suction pump 12 sucked the sample liquid and introduced it into the sample loop 24 and stored it (Fig. 3). In the next operation 2, the injection valve 14 was switched to mode B to connect to the metering pump 10 and the sample loop 24, and the metering pump 10 was driven to measure and send 3.5 mL of liquid, and the sample liquid in the sample loop 24 was washed into the dilution container 18 together with the dilution liquid (Fig. 4). In order to increase the mixing efficiency, a stirrer covered with Teflon (registered trademark) was placed in the dilution container 18.

[0045] Next, in the second dilution step, the three-way valve 16 was switched to mode D by operation 3, and the injection valve 14 was switched to mode A, and the primary dilution solution in the dilution container 18 was introduced into the sample loop 24 by the suction pump 12 and stored therein (FIG. 5). Furthermore, the injection valve 14 was switched to mode B by operation 4, and the primary dilution solution remaining in the dilution container 18 was aspirated and discharged by the suction pump 12 (FIG. 6). Then, the injection valve 14 was switched to mode A by operation 5, and 3.5 mL of the dilution solution was introduced into the dilution container 18 by the dilution metering pump 10 (FIG. 7). Then, the injection valve 14 was switched to mode B by operation 6, and the washing solution was discharged by the suction pump 12, and the dilution container 18 was emptied (FIG. 6). This series of washing steps 4-6 was performed three times in total. Then, in operation 7, the primary diluted sample solution stored in the sample loop 24 was metered with the metering pump 10 to be introduced into the dilution container 18 and diluted to obtain a secondary diluted solution, completing the second-stage dilution. This two-stage dilution operation was repeated 5 times to dilute the solution by 120,000 times, and the results of analyzing the obtained secondary diluted solutions (number of samples: 5) by flow injection fluorometry are shown in Table 6. The analysis was performed using a combination of a pump G1312A manufactured by HP, an autosampler G1329A, and a fluorometry device G7121B manufactured by Agilent Technologies, Inc., with ultrapure water as the carrier solution, 100 μL of sample volume, an excitation wavelength of 280 nm, and a fluorescence wavelength of 350 nm. [Table 6]

[0046] In the two-step dilution, the average value of the peak area was 41.38, the standard deviation was 0.24, and the relative standard deviation was 0.58%. In the same apparatus, when the tryptophan concentration in the diluted sample solution was 7.1 ppm in the one-step dilution condition, the relative standard deviation was 0.2%. In the case of analyzing a 20 ppb tryptophan standard solution (aqueous solution) by the flow injection fluorometry, the analytical accuracy was 0.2% when the analysis was repeated five times. Therefore, according to the dilution method of this embodiment, it was shown that a wide range of dilution, including a high dilution rate of more than 100,000 times, can be easily performed with a simple apparatus with a high accuracy of less than 0.6% relative standard deviation. In addition, by further improving the accuracy of the metering pump, it is possible to further improve the accuracy.

[0047] In addition, in order to evaluate the accuracy of the dilution operation, a comparison was made with a dilution method in which a microsyringe was used to measure the sample liquid as a comparative example. In the following comparative examples, the compounds, devices, and conditions used were the same as those in Example 1, unless otherwise specified. The dilution conditions were the same as in the example, with a 2500 ppm tryptophan aqueous solution diluted 120,000 times using ultrapure water as the diluent. In the first dilution step, a 1 μL microsyringe (Hamilton 7101KH) was used to collect the sample solution, which was then placed in a glass container, and 120 mL of ultrapure water was measured and added using a double plunger metering pump. The diluted sample solution was analyzed by flow injection fluorometry (excitation wavelength 280 nm, fluorescence wavelength 350 nm). This series of operations from dilution to analysis was repeated five times, and the relative standard deviation of the area of ​​the peak where 20 ppb of tryptophan was detected in the diluted sample solution was calculated. The relative standard deviation obtained was 1.7%, which was higher than the 0.58% obtained in the example when the solution was diluted 120,000 times.

[0048] Next, a 120,000-fold dilution was performed under the same conditions of sample volume and dilution volume as in the example, that is, diluting 10 μL of sample volume with 3.5 mL of dilution solution twice. Specifically, a 2500 ppm tryptophan sample solution was collected using a 10 μL microsyringe (Agilent Technologies, Inc., 9301-0725), placed in a glass container, and weighed. 3.5 mL of ultrapure water was measured and added as dilution solution using a double plunger type metering pump and weighed. Before the next second-stage dilution, in order to remove the residual influence of the sample solution remaining in the microsyringe, the microsyringe was washed 25 times with ultrapure water, and then the first dilution solution was washed 25 times to collect 10 μL, and 3.5 mL was measured and added to another glass container using the above-mentioned plunger type pump and weighed. The obtained diluted sample solution was analyzed by flow injection fluorometry (excitation wavelength 280 nm, fluorescence wavelength 350 nm). This series of operations from dilution to analysis was repeated five times. The relative standard deviation obtained was 1.6%, which was larger than the 0.58% of the Example. To investigate the cause of this larger relative standard deviation, the measurement accuracy of the sample liquid and diluent was evaluated. The dilution ratio was calculated from the weight values ​​of the sample liquid and diluent measured using a syringe and a plunger pump. This operation was repeated five times to obtain the relative standard deviation of the dilution ratio based on the measured values, which was 0.3%. This was thought to be due to the influence of the accuracy of the sample liquid and diluent collection amount, as well as the large influence of the residual sample liquid and primary diluent despite the washing and co-washing operations being performed 25 times each. In addition, when the washing and co-washing operations were reduced to 10 and 20 times, respectively, the accuracy significantly decreased as shown in Table 6, and the influence of the residual liquid became even larger, so many times were required, but even if it was increased to 25 times, the accuracy remained in the upper 1% range.

[0049] In addition, a comparison was also made under low dilution conditions (350 times), in which a 10 μL sample volume was diluted once with 3.5 mL of dilution solution. Specifically, a 2500 ppm tryptophan sample solution was collected using a 10 μL microsyringe, placed in a glass container, and then weighed. 3.5 mL of ultrapure water was measured using the above-mentioned plunger pump as the dilution solution, and then weighed. The obtained diluted sample solution was analyzed by flow injection fluorometry (excitation wavelength 280 nm, fluorescence wavelength 350 nm). This series of operations from dilution to analysis was repeated five times. The obtained relative standard deviation was 0.5%, which was higher than the 0.2% of the example. In order to investigate the cause of this large relative standard deviation, the relative standard deviation of the dilution ratio based on the measured values ​​of the sample solution and dilution solution was calculated in the same manner as in the above two-step dilution test, and the result was almost the same at 0.6%, suggesting that it is due to the accuracy of the amount of sample solution collected using a 10 μL syringe.

[0050] From the above, according to this embodiment, it is possible to perform multi-stage dilution of the sample liquid with high accuracy over a wide range of high magnifications. In addition, in terms of operation, since complicated operations such as washing the syringe and washing the diluted sample liquid several tens of times are not required, it can be performed easily. Furthermore, according to this embodiment, the sample liquid and the primary dilution liquid can be measured in accurate amounts using the same quantitative tube such as a sample loop, and the primary dilution liquid and the secondary dilution liquid can be stored in the same dilution container, so that the number of pipes and containers can be reduced, and it is also excellent in terms of convenience, simplicity of the device, and cost. [Explanation of symbols]

[0051] 1, 3, 4 Sample dilution device 5 Chemical analyzer 6, 7, 8 Chemical Analysis Systems 10 Metering pump 12 Suction pump 14 Injection valve 16 Three-way valve 18 Dilution Container 20 Sample liquid container 22 Diluent container 24 Sample Loops 30 Control device 31, 33 Raw material liquid container 35 Reactor 37 Switching valve 39 Product container 40 Measuring Cell 41, 43 Pump L1 Sample fluid flow path L2 diluent flow path L3 Dilution sample flow path L4 Extraction channel L5 Exhaust flow path L6 Common flow path L7 Product flow path

Claims

1. a container for supplying a sample liquid to be diluted and a diluent; an extraction flow path for extracting the mixed liquid from the container; a sample liquid flow path for supplying the sample liquid; a common flow path connected to the sample liquid flow path and the extraction flow path; A diluent flow path for supplying the diluent; A liquid delivery means is provided in the diluent flow path and delivers a predetermined amount of diluent; a dilution sample liquid flow path for supplying a sample liquid and a dilution liquid to the container; a first flow path switch for switching a flow path connected to the common flow path between the sample liquid flow path and the extraction flow path; a discharge flow path for discharging a liquid supplied from the common flow path; Discharge means provided in the discharge flow path; a constant amount storage flow path for temporarily storing a constant amount of the liquid to be supplied; a second flow path switch capable of switching among a flow path 1 that connects from the common flow path to the discharge flow path via the fixed quantity storage flow path, a flow path 2 that connects from the diluent flow path to the diluted sample liquid flow path via the fixed quantity storage flow path, a flow path 3 that connects from the common flow path to the discharge flow path without passing through the fixed quantity storage flow path, and a flow path 4 that connects from the diluent flow path to the diluted sample liquid flow path without passing through the fixed quantity storage flow path; A sample dilution device comprising:

2. a reactor, a raw material liquid supply flow path for supplying a raw material liquid to the reactor, and a product supply flow path for supplying a liquid containing a product produced in the reactor to the sample liquid flow path; 2. The sample dilution device according to claim 1, further comprising:

3. a first flow path switcher for switching a flow path connected to the common flow path between each of the sample liquid flow paths and an extraction flow path; The sample dilution device of claim 1, further comprising a second flow path switch connected in series such that a flow path supplied from the diluent flow path and which may or may not pass through the fixed quantity storage flow path and a flow path supplied from the common flow path and which may or may not pass through the fixed quantity storage flow path are in parallel, and the most upstream second flow path switch is connected to the diluent flow path and the common flow path, and the most downstream second flow path switch is connected to the diluted sample liquid flow path and the discharge flow path.

4. a step 1 of connecting the sample liquid flow path to the common flow path by the first flow path switch, and forming the flow path into the flow path 1 by the second flow path switch, and storing the sample liquid supplied from the sample liquid flow path in the fixed quantity storage flow path by the discharge means; a step 2 of switching the second flow path switch to flow path 2, and supplying a predetermined amount of diluent by the liquid delivery means, so that the sample liquid and the diluent stored in the fixed amount storage flow path are supplied from the diluted sample liquid flow path to the container; a step 3 of switching the first flow path switch to connect the extraction flow path to the common flow path and the second flow path switch to connect to flow path 1, and storing the mixed liquid in the container in the fixed quantity storage flow path by the discharge means; a step 4 of switching the first flow path switch to connect the withdrawal flow path to the common flow path and the second flow path switch to connect to the flow path 3, and discharging the mixed liquid in the container by the discharge means; a step 5 of switching the second flow path switch to connect to the flow path 4, and supplying a predetermined amount of diluent from the diluted sample liquid flow path to the container by the liquid supplying means; a step 6 of switching the first flow path switch to connect the extraction flow path to the common flow path and the second flow path switch to connect to the flow path 3, and discharging the entire amount of the diluent in the container by the discharge means; a step 7 of switching the second flow path switch to connect to the flow path 2, and supplying a predetermined amount of diluent by the liquid supplying means, and supplying the mixed liquid and diluent stored in the fixed amount storage flow path from the diluted sample liquid flow path to the container; 2. The sample dilution device according to claim 1, further comprising a function for executing steps 1 to 7 in that order.

5. The sample dilution device according to claim 4, further comprising a function of repeating steps 3-7 one or more times after step 1-7.

6. A sample dilution method for diluting a sample liquid using the sample dilution device according to claim 1 or 2, comprising the steps of: a step 1 of connecting the sample liquid flow path to the common flow path by the first flow path switch, and forming the flow path 1 by the second flow path switch, supplying the sample liquid from the sample liquid flow path, and storing the sample liquid in the fixed quantity storage flow path by the discharge means; A step 2 of switching the second flow path switch to flow path 2, supplying a predetermined amount of diluent by the liquid supplying means, and supplying the sample liquid and diluent stored in the fixed amount storage flow path from the diluted sample liquid flow path to the container. a step 3 of switching the first flow path switch to connect the extraction flow path to the common flow path and the second flow path switch to connect to flow path 1, and storing the mixed liquid in the container in the fixed quantity storage flow path by the discharge means; a step 4 of switching the first flow path switch to connect the withdrawal flow path to the common flow path and the second flow path switch to connect to the flow path 3, and discharging the mixed liquid in the container by the discharge means; a step 5 of switching the second flow path switch to connect to the flow path 4, and supplying a predetermined amount of diluent from the diluted sample liquid flow path to the container by the liquid supplying means; a step 6 of switching the first flow path switch to connect the extraction flow path to the common flow path and the second flow path switch to connect to the flow path 3, and discharging the entire amount of the diluent in the container by the discharge means; a step 7 of switching the second flow path switch to connect to the flow path 2, and supplying a predetermined amount of diluent by the liquid supplying means, and supplying the mixed liquid and diluent stored in the fixed amount storage flow path from the diluted sample liquid flow path to the container; A sample dilution method characterized by carrying out steps 1 to 7 in this order.

7. The method for diluting a sample according to claim 6, wherein after step 1-7, step 3-7 is repeated one or more times.

8. A chemical analysis system comprising the sample dilution device according to any one of claims 1 to 3 and a chemical analysis device that analyzes the mixed liquid in the container, A chemical analysis system, characterized in that the container is a measurement cell of the chemical analysis device.

9. A chemical analysis system comprising the sample dilution device according to any one of claims 1 to 3 and a chemical analysis device that analyzes the mixed liquid in the container, a first discharge means for discharging the mixed liquid in the container; a supply means for supplying the mixed liquid discharged by the first discharge means to a measurement cell of the chemical analysis device; and a second discharge means for discharging the mixed liquid supplied by the supply means from the measurement cell. A chemical analysis system comprising:

10. A chemical analysis system comprising the sample dilution device according to any one of claims 1 to 3 and a chemical analysis device that analyzes the mixed liquid in the container, a discharge means for discharging the mixed liquid in the container; and a supply means for supplying the mixed liquid discharged by the discharge means to the chemical analysis device. A chemical analysis system comprising:

11. A chemical analysis system comprising the sample dilution device according to claim 4 or 5 and a chemical analysis device that analyzes the mixed liquid in the container, A chemical analysis system comprising: a container serving as a measurement cell of the chemical analysis device; and performing steps 1 to 7 in this order to continuously dilute and measure the sample liquid.

12. A chemical analysis system comprising the sample dilution device according to claim 4 or 5 and a chemical analysis device that analyzes the mixed liquid in the container, a first discharge means for discharging the mixed liquid in the container, a supply means for supplying the mixed liquid discharged by the first discharge means to a measurement cell of the chemical analysis device, and a second discharge means for discharging the mixed liquid supplied by the supply means from the measurement cell, A chemical analysis system characterized in that the sample liquid is diluted by performing steps 1 to 7 in this order, and the first discharge means, the supply means, and the second discharge means are used to simultaneously or continuously dilute and measure the sample liquid.

13. A chemical analysis system comprising the sample dilution device according to claim 4 or 5 and a chemical analysis device that analyzes the mixed liquid in the container, a discharge means for discharging the mixed liquid in the container, and a supply means for supplying the mixed liquid discharged by the discharge means to the chemical analysis device, A chemical analysis system comprising: a step of diluting a sample liquid by carrying out steps 1 to 7 in this order; and a step of simultaneously or continuously diluting and measuring the sample liquid by using the discharge means and the supply means.

14. 12. The chemical analysis system according to claim 11, wherein the dilution and measurement of the sample liquid are carried out online.

15. 13. The chemical analysis system according to claim 12, wherein the dilution and measurement of the sample liquid are carried out online.

16. 14. The chemical analysis system according to claim 13, wherein the dilution and measurement of the sample liquid are carried out online.

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