Online Sampling System

Abstract

To provide an online sampling system for collecting a sample from a sample source and injecting it on-line into the mobile phase of a liquid chromatograph (hereafter, LC), with which it is made possible to inject the sample of a sample source into the LC while maintaining the pressure state of the sample source.SOLUTION: An online sampling system has a second sample loop 12, separately from a first sample loop 18, which is provided in an injection unit 2 for injecting a sample to the LC. The online sampling system further includes a flow path for sample collection that is a closed system for pulling in a sample from a sample source into the second sample loop through a sample source flow path 52, and a flow path 26 for sample provision that is selectively constructed in order to separate the second sample loop from the sample source flow path while maintaining the closed system state of the sample source flow path, fluid-connect the second sample loop to the injection unit, and send the sample held in the second sample loop into the injection unit.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to an online sampling system that collects a sample from a sample source and injects it online into the mobile phase of a liquid chromatograph (hereinafter referred to as LC). [Background technology]

[0002] LC is an analytical technology not only used in various fields such as pharmaceuticals, food, and chemistry, but also in a wide range of processes, from upstream (research and development) to downstream (manufacturing and quality control) in each of these fields. In manufacturing and quality control processes, the adoption of Process Analytical Technology (PAT) using LC is being promoted to monitor manufacturing processes as automatically and continuously as possible and ensure that the required product quality is guaranteed. Introducing PAT not only improves the reliability and robustness of manufacturing processes, but also reduces costs. For this reason, the adoption of PAT is progressing in the petroleum and chemical industries, and its introduction is also being considered in the pharmaceutical and electronics industries.

[0003] One known online monitoring system using an LC is one that uses a flow vial (see Patent Document 1). In a system using a flow vial, the flow vial is placed in an autosampler of the LC, and a sample supplied from a sample source to the flow vial is injected into the LC by the autosampler. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Patent Publication No. 2021-063835 Summary of the Invention [Problem to be solved by the invention]

[0005] When attempting to monitor a manufacturing process under high pressure using a flow vial-based system, the high-pressure sample source is fluidly connected to the flow vial, resulting in high pressure within the flow vial. However, because the autosampler needle penetrates the septum of the flow vial when injecting the sample supplied to the flow vial into the LC, the system from the sample source to the flow vial cannot be considered a completely closed system. As a result, it is difficult to maintain the sample source at the required high pressure, which may affect the reaction of the sample during the manufacturing process.

[0006] The present invention has been made in view of the above problems, and has as its object to make it possible to inject a sample from a sample source into an LC while maintaining the pressure state of the sample source. [Means for solving the problem]

[0007] The online sampling system of the present invention is an online sampling system for collecting a sample from a sample source and injecting it into a mobile phase flowing through an analytical flow path of an LC, comprising: an injection unit including a first sample loop for temporarily holding a sample and an injection valve for switching the first sample loop between a state where it is incorporated into the analysis flow path and a state where it is separated from the analysis flow path; a sample supply channel fluidly connected to the injection section for supplying a sample to the injection section; a pump unit for suctioning and discharging liquid; a second sample loop provided separately from the first sample loop; a sample source flow path leading to a sample source; a path construction unit including one or more switching valves, configured to be able to selectively construct a plurality of fluid flow paths in the online sampling system by switching the one or more switching valves; The path construction unit a sample collection path fluidly connecting the sample source flow path and the pump unit in a closed system with the second sample loop interposed therebetween, for drawing a sample from the sample source into the second sample loop by the pump unit; and a sample supply path for disconnecting the second sample loop from the sample source flow path while maintaining the sample source flow path in a closed system state, fluidly connecting the pump unit or a pump other than the pump unit to the sample supply flow path with the second sample loop interposed therebetween, and supplying the sample held in the second sample loop to the injection unit through the sample supply flow path by the pump unit or the other pump; The system is configured to be able to selectively configure the

[0008] Here, a closed system means a system in which there is no location within the system where fluid can circulate between the system and the outside, and a completely closed internal space is formed. "Maintaining the closed state of the sample source flow path" means that the closed state within the system including the sample source flow path is always maintained before and after the connection destination of the sample source flow path is switched. [Effects of the Invention]

[0009] According to the online sampling system of the present invention, a second sample loop is provided in addition to a first sample loop provided in an injection section for injecting a sample into an LC, and a sample collection path, which is a closed system for drawing a sample from the sample source into the second sample loop through a sample source flow path, and a sample supply path for sending the sample held in the second sample loop to the injection section by disconnecting the second sample loop from the sample source flow path while maintaining the closed system state of the sample source flow path and fluidly connecting the second sample loop to the injection section can be selectively constructed, so that the sample from the sample source can be supplied to the injection section and injected into the LC while maintaining the pressure state of the sample source. [Brief explanation of the drawings]

[0010] [Figure 1] FIG. 1 is a flow path configuration diagram showing an embodiment of an online sampling system. [Figure 2] FIG. 10 is a diagram showing an example of a flow path configuration when a sample collection path is constructed in the same embodiment. [Figure 3] FIG. 10 is a diagram showing an example of a flow path configuration when a sample supply path is constructed in the same embodiment. [Figure 4] FIG. 10 is a diagram showing an example of a flow path configuration when a diluted sample is drawn into a first sample loop in this embodiment. [Figure 5] 10 is a diagram showing an example of a flow path configuration when a cleaning liquid is sent from a pump unit to clean the inside of the flow path. FIG. [Figure 6] FIG. 10 is a diagram showing an example of a flow path configuration when a sample held in a first sample loop is injected into a mobile phase of an LC. [Figure 7] FIG. 10 is a diagram showing an example of a flow path configuration when a pre-treatment unit cleaning path is constructed in the same embodiment. [Figure 8] FIG. 10 is a diagram showing another example of the flow path configuration when a path for cleaning a pre-treatment unit is constructed in the same embodiment. [Figure 9] FIG. 10 is a diagram showing an example of a flow path configuration when the inside of the flow path is washed with a solvent supplied by a liquid feed pump in the same embodiment. [Figure 10] 10 is a flowchart illustrating an example of a sampling operation in which a sample from a sample source is injected into a mobile phase of an LC in the same embodiment. [Figure 11] FIG. 10 is a flow path configuration diagram showing another embodiment of the online sampling system. [Figure 12] FIG. 10 is a diagram showing an example of a flow path configuration when a sample collection path is constructed in the same embodiment. [Figure 13] FIG. 10 is a diagram showing an example of a flow path configuration when a sample supply path is constructed in the same embodiment. [Figure 14] FIG. 10 is a flow path configuration diagram showing yet another embodiment of the online sampling system. [Figure 15] FIG. 10 is a diagram showing an example of a flow path configuration when a sample collection path is constructed in the same embodiment. [Figure 16]FIG. 10 is a diagram showing an example of a flow path configuration when a sample supply path is constructed in the same embodiment. [Figure 17] FIG. 10 is a flow path configuration diagram showing yet another embodiment of the online sampling system. [Figure 18] FIG. 10 is a diagram showing an example of a flow path configuration when a sample collection path is constructed in the same embodiment. [Figure 19] FIG. 10 is a diagram showing an example of a flow path configuration when a sample supply path is constructed in the same embodiment. DETAILED DESCRIPTION OF THE INVENTION

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

[0012] The online sampling system 1 of this embodiment includes an injection section 2, a pump section 4, switching valves 6, 8, and 10, a sample loop 12 (second sample loop), a container section 14, a drain port 16, and a control section 17.

[0013] The injection unit 2 is used to inject a sample into a mobile phase flowing through an LC analysis flow path 100 equipped with a separation column 102, a detector 104, etc. The injection unit 2 includes a sample loop 18 (first sample loop) for temporarily holding the sample, an injection valve 20 for switching the sample loop 18 between a state in which it is incorporated into the analysis flow path 100 and a state in which it is detached from the analysis flow path 100, and a sampling flow path 24 equipped with a needle 22 that moves three-dimensionally at its tip. The injection valve 20 is a two-position valve with six ports, numbered 1 to 6, arranged counterclockwise. Adjacent ports 1 and 2 of the injection valve 20 are fluidly connected to the upstream and downstream flow paths of the analysis flow path 100, respectively. Ports 3 and 6 of the injection valve 20 are fluidly connected to one end and the other end of the sample loop 18, respectively. Port 4 of the injection valve 20 is fluidly connected to the sampling flow path 24, and one end of a sample supply flow path 26 is connected to port 5 adjacent to port 4. The other end of the sample supply flow channel 26 is fluidly connected to the port 6 of the switching valve 6. The sample supply flow channel 26 is a flow channel for supplying the sample to the injection part 2.

[0014] The pump unit 4 is fluidly connected to port 1 of the switching valve 6 via a pump flow path 36. The pump unit 4 includes two syringe pumps 28 and 30 and two three-port valves 32 and 34. The syringe pumps 28 and 30 have different cylinder capacities. The pump unit 4 can fluidly connect either the syringe pumps 28 or 30 to the pump flow path 36 via the three-port valves 32 and 34. The pump unit 4 can also supply a cleaning liquid from either the syringe pumps 28 or 30 through the pump flow path 36. Note that the pump unit 4 does not necessarily have to include two syringe pumps, and may include only one syringe pump.

[0015] The container section 14 is configured to allow a plurality of containers 54 to be set therein. The containers 54 that can be set in the container section 14 include empty containers that can be used to dilute samples, as well as sample containers that hold samples. The drain port 16 is a port that allows the needle 22 to access and discharge the liquid dispensed from the needle 22 to a drain. The needle 22 of the injection section 2 can access any of the containers 54 set in the container section 14 and the drain port 16.

[0016] Each of the switching valves 6, 8, and 10 is a two-position valve having six ports numbered 1 to 6 in a counterclockwise direction.

[0017] Port 2 of the switching valve 6 is fluidly connected to port 3 of the switching valve 8 via flow path 38, port 4 of the switching valve 6 is fluidly connected to port 1 of the switching valve 8 via flow path 44, and port 5 of the switching valve 6 is fluidly connected to port 6 of the switching valve 8 via flow path 46. Port 3 of the switching valve 6 is connected to a solvent supply flow path 42 equipped with a liquid delivery pump 40 provided separately from the pump unit 4. The liquid delivery pump 40 can supply the solvent through the solvent supply flow path 42.

[0018] Ports 2 and 5 of the switching valve 8 are fluidly connected to one end and the other end of the sample loop 12, respectively. Port 4 of the switching valve 8 is fluidly connected to port 4 of the switching valve 10 via a pretreatment flow path 48. A pretreatment unit 50 is provided on the pretreatment flow path 48. The pretreatment unit 50 is a unit for pretreatment of the sample drawn into the sample loop 12 from the sample source. Examples of the pretreatment unit 50 include a filter for removing unnecessary substances from the sample, and a redissolution device for redissolving the sample precipitated in the flow path. Possible redissolution devices include devices that generate ultrasound, low-frequency vibration, heat, electric fields, and magnetic fields.

[0019] Ports 1, 2, and 6 of the switching valve 10 are closed ports. Port 3 of the switching valve 10 is fluidly connected to a sample source flow path 52 that leads to a sample source.

[0020] The switching valves 6, 8, and 10 constitute a path construction unit for constructing various fluid flow paths in the online sampling system 1. The fluid flow paths constructed by the path construction unit consisting of the switching valves 6, 8, and 10 will be described below.

[0021] As shown in FIG. 2, by fluidically connecting ports 1 and 2 of switching valve 6, fluidly connecting ports 2 and 3 and ports 4 and 5 of switching valve 8, and fluidly connecting ports 3 and 4 of switching valve 10, the pump unit 4 and the sample source channel 52 are fluidly connected in a closed system with the sample loop 12 interposed therebetween. In this state, by driving one of the syringe pumps of the pump unit 4 (syringe pump 28 in the figure) for suction, the sample from the sample source is drawn into the sample loop 12 through the sample source channel 52 and the pretreatment channel 48. In other words, by setting the switching valves 6, 8, and 10 to the state shown in FIG. 2, a sample collection path is established for drawing the sample from the sample source into the sample loop 12 by the pump unit 4. With the sample collection path established, the system from the sample source channel 52 to the pump unit 4 is a closed system, so the pressure in the sample source 52 can be maintained without reduction.

[0022] 3, by fluidically connecting ports 3-4 and 5-6 of switching valve 6 and fluidically connecting ports 1-2 and 5-6 of switching valve 8, solvent supply channel 42 and sample supply channel 26 are fluidly connected with sample loop 12 interposed therebetween. By sending solvent using liquid feed pump 40 in this state, the sample held in sample loop 12 is supplied to injection unit 2 together with the solvent from liquid feed pump 40. In other words, by setting switching valves 6, 8, and 10 to the state shown in FIG. 3, a sample supply path is established for supplying the sample held in sample loop 12 to injection unit 2 by liquid feed pump 40. At this time, by fluidly communicating ports 4 and 5 of injection valve 20 of injection unit 2 and accessing needle 22 to an empty container 54 set in container 14, the sample and solvent supplied to injection unit 2 through sample supply channel 26 can be contained in container 54, and the sample can be diluted in container 54. The sample dilution rate can be adjusted by the liquid supply flow rate of liquid supply pump 40.

[0023] 3, when the sample supply path is constructed, port 3 of the switching valve 10, to which the sample source flow path 52 is fluidly connected, is fluidly connected to the closed port 2, so that a closed system state is maintained even after the sample source flow path 52 is disconnected from the sample loop 12. Note that even when ports 3 and 4 of the switching valve 10 are fluidly connected with each other when the sample supply path is constructed, it is possible to maintain a closed system state within the system including the sample source.

[0024] 4, by fluidly communicating ports 1-6 of switching valve 6, pump unit 4 is fluidly connected to sampling flow path 24, and an intake / discharge path is established for the intake and discharge of fluid by pump unit 4 via needle 22. In the example of FIG. 4, needle 22 is accessed to drain port 16. In this state, by supplying a cleaning solution from one of the syringe pumps of pump unit 4 (syringe pump 30 in the figure), the inside of the flow path from pump unit 4 to needle 22 can be cleaned.

[0025] 5, a sample loop 18 can be incorporated into the intake / exhaust path by fluidly connecting ports 3 and 4 and ports 5 and 6 of injection valve 20 of injection unit 2. In this state, needle 22 is made to access container 54 containing a diluted sample, and one of the syringe pumps of pump unit 4 (syringe pump 30 in the figure) is driven for suction, thereby drawing the sample from container 54 into sample loop 18.

[0026] After the sample is drawn into the sample loop 18, as shown in Figure 6, the sample held in the sample loop 18 can be injected into the LC mobile phase by fluidly connecting ports 1-6 and ports 2-3 of the injection valve 20 of the injection section 2 and incorporating the sample loop 18 into the analysis flow path 100.

[0027] In addition to the above, the path construction unit made up of the switching valves 6, 8, and 10 can construct various cleaning paths.

[0028] 7, by fluidly communicating ports 2 and 3 of switching valve 6, fluidly communicating ports 3 and 4 of switching valve 8, and fluidly communicating ports 4 and 5 of switching valve 10, a pretreatment unit washing path is constructed in which the solvent supply path 42, the pretreatment path 48, and the drain are fluidly connected in series. By constructing such a pretreatment unit washing path, the pretreatment unit 50 on the pretreatment path 48 can be washed with the solvent from the liquid feed pump 40.

[0029] 8, by fluidically connecting ports 2 and 3 of switching valve 6, fluidly connecting ports 2 and 3 and ports 4 and 5 of switching valve 8, and fluidly connecting ports 4 and 5 of switching valve 10, a pretreatment unit washing path is constructed in which the solvent supply path 42, sample loop 12, pretreatment path 48, and drain are fluidically connected in series. In the pretreatment unit washing path of FIG. 8, the inside of the sample loop 12 as well as the pretreatment path 48 can be washed with solvent from the liquid feed pump 40.

[0030] In the pretreatment unit cleaning path shown in Figures 7 and 8, the solvent can be flowed in the opposite direction to the flow of the sample when drawing the sample from the sample source into the sample loop 12 within the pretreatment unit 50, thereby achieving a high cleaning effect for the pretreatment unit 50.

[0031] 9, by fluidly communicating ports 3-4 and 5-6 of switching valve 6 and by fluidly communicating ports 1-6 of switching valve 8, a path is constructed for supplying the solvent from liquid delivery pump 40 to injection unit 2 via flow paths 44, 46 and sample supply flow path 26. In this state, by accessing needle 22 of injection unit 2 to drain port 16 and supplying solvent to injection unit 2 by liquid delivery pump 40, it is possible to wash not only flow paths 44, 46 and sample supply flow path 26, but also sample loop 18 and sampling flow path 24 of injection unit 2.

[0032] The operations of the injection unit 2, pump unit 4, switching valves 6, 8, and 14, and liquid delivery pump 40 are controlled by a control unit 17 (see FIG. 1). The control unit 17 is a function realized by executing a computer program in a computer device equipped with a CPU (Central Processing Unit) and an information storage device. The control unit 17 is configured to control the operations of the injection unit 2, pump unit 4, switching valves 6, 8, and 14, and liquid delivery pump 40, thereby collecting a sample from a sample source, supplying it to the injection unit 2, and, after performing pretreatment such as diluting the sample as necessary, executing a sampling operation in which the sample is injected into the mobile phase flowing through the analysis flow path 100.

[0033] FIG. 10 shows an example of the sampling operation.

[0034] The control unit 17 constructs a sample collection path as shown in FIG. 2 using the switching valves 6, 8, and 14 (step 101), and connects either the syringe pump 28 or 30 of the pump unit 4 to the pump flow path 36 and drives it for suction, thereby drawing the sample from the sample source into the sample loop 12 (second sample loop) (step 102).

[0035] 3 using the switching valves 6, 8, and 14 (step 103), and supplies the sample held in the sample loop 12 together with the solvent to the injection unit 2 via the sample supply flow path 26 by sending the solvent from the liquid supply pump 40 (step 104). At this time, the needle 22 of the injection unit 2 is made to access the empty container 54 of the container unit 14, and the sample and solvent supplied to the injection unit 2 via the sample supply flow path 26 are temporarily stored in the container 54, and the sample is diluted in the container 54.

[0036] After the sample and solvent are stored in the container 54, an operation of stirring the inside of the container 54 can be performed as necessary. Stirring the inside of the container 54 can be performed by fluidly connecting either the syringe pump 28 or 30 of the pump unit 4 to the sampling channel 24 by fluidly communicating between ports 1-6 of the switching valve 6 while the needle 22 is accessing the container 54, and causing the syringe pump 28 or 30 to repeatedly perform suction and discharge operations. Furthermore, thereafter, the needle 22 is accessing the drain port 16, and a cleaning solution is supplied from the pump unit 4, thereby cleaning the sample supply channel 26 and the sampling channel 24 (see FIG. 4).

[0037] After storing the sample and solvent in the container 54 and performing flow path cleaning, etc. as necessary, the control unit 17 establishes an intake / exhaust path with the sample loop 18 between the pump unit 4 and the sampling flow path 24 while accessing the needle 22 to the storing container 54, and causes one of the syringe pumps 28 or 30 of the pump unit 4 to perform a suction operation, thereby drawing the sample into the sample loop 18 (see FIG. 5). The control unit 17 then switches the injection port 20 to incorporate the sample loop 18 into the analysis flow path 100, thereby injecting the sample into the LC mobile phase (step 105). After injecting the sample into the LC mobile phase, the control unit 17 establishes cleaning paths as shown in FIGS. 7 to 9 as necessary, and performs cleaning within each flow path of the system 1 (step 106). Note that cleaning of the pretreatment unit 50 using the pretreatment unit cleaning path shown in FIGS. 7 and 8 can be performed at any time after the sample has been supplied to the injection unit 2.

[0038] In the above embodiment, various fluid flow paths can be constructed using a path construction unit consisting of three switching valves 6, 8, and 10, but the present invention is not limited to this. In short, it is sufficient that the system including the sample source is always maintained as a closed system, and that at least a sample collection path that can collect a sample from the sample source to the sample loop 12 and a sample supply path that can supply a sample from the sample loop 12 to the injection unit 2 can be constructed.

[0039] Fig. 11 is a configuration diagram showing another embodiment of the online sampling system. In the embodiment described below, the same components as those in the online sampling system 1 described with reference to Figs. 1 to 10 are given the same reference numerals, and detailed description thereof will be omitted.

[0040] In the online sampling system 1' of this embodiment, two switching valves 56 and 58 realize a path construction unit for constructing various fluid flow paths.

[0041] Both switching valves 56 and 58 are two-position valves with six ports numbered 1 to 6 in a counterclockwise direction. Sample supply flow path 26 leading to injection section 2 is fluidly connected to port 1 of switching valve 56, and pump flow path 36 leading to pump section 4 is fluidly connected to port 2 of switching valve 56. Port 3 of switching valve 56 is fluidly connected to port 1 of switching valve 58 via flow path 60, and port 6 of switching valve 56 is fluidly connected to port 5 of switching valve 58 via flow path 62. Ports 4 and 5 of switching valve 56 are closed.

[0042] A sample source flow path 52 leading to a sample source is fluidly connected to port 2 of a switching valve 58. A pre-treatment unit 50 is provided on the sample source flow path 52. One end and the other end of a sample loop 12 are fluidly connected to ports 3 and 6 of the switching valve 58, respectively. A solvent supply flow path 42 equipped with a liquid delivery pump 40 is fluidly connected to port 4 of the switching valve 58.

[0043] 12, in this online sampling system 1', by fluidly communicating ports 2 and 3 of switching valve 56 and fluidly communicating ports 1 and 2 and ports 2 and 3 of switching valve 58, a sample collection path is constructed that fluidly communicates between pump unit 4 and sample source flow path 52 with sample loop 12 interposed therebetween. In this state, by driving either syringe pump 28 or 30 of pump unit 4 for suction, the sample from the sample source can be drawn into sample loop 12.

[0044] Furthermore, as shown in FIG. 13 , by fluidically connecting ports 1-6 of switching valve 56 and ports 3-4 and 5-6 of switching valve 58, a sample supply path is established in which the solvent supply flow path 42 and the sample supply flow path 26 are fluidically connected with the sample loop 12 interposed therebetween. In this state, by sending solvent using the liquid supply pump 40, the sample held in the sample loop 12 can be supplied to the injection unit 2 together with the solvent. At this time, by fluidically connecting ports 4-5 of injection valve 20 of injection unit 2 and accessing the needle 22 to an empty container 54 set in the container 14, the sample and solvent supplied to injection unit 2 through the sample supply flow path 26 can be contained in container 54, and the sample can be diluted in container 54. The sample dilution rate can be adjusted by adjusting the liquid supply flow rate of liquid supply pump 40. Another dilution method is to adjust the dilution rate during liquid supply by changing the piping capacity of the flow path. For example, if a pipe with a capacity of 100 mL is compared with a pipe with a capacity of 50 mL, the sample will be more diluted when the 100 mL pipe is used. In other words, by using a pipe with a capacity that matches the desired dilution rate in the flow path, the sample can be further diluted than when the liquid delivery flow rate of the liquid delivery pump 40 is adjusted.

[0045] Furthermore, although not shown in the figure, by fluidly connecting ports 1 and 2 of the switching valve 56, the pump unit 4 can be fluidly connected to the sampling flow path 24, making it possible to draw the sample stored in the container 54 into the sample loop 18, or to supply a cleaning liquid from the pump unit 4 to the sampling flow path 24 to clean the inside of the flow path.

[0046] Fig. 14 is a configuration diagram showing yet another embodiment of the online sampling system. In the embodiment described below, the same components as those in the online sampling system 1 described with reference to Figs. 1 to 10 are given the same reference numerals, and detailed description thereof will be omitted.

[0047] In the online sampling system 1 ″ of this embodiment, two switching valves 64 and 66 realize a path construction unit for constructing various fluid flow paths.

[0048] The switching valve 64 is a two-position valve with ports 1 to 6 arranged counterclockwise. The switching valve 66 is a seven-port valve with a common port in the center and ports 1 to 6 arranged counterclockwise around the common port, and is configured to selectively connect the center port to any one of ports 1 to 6.

[0049] Pump channel 36 leading to pump section 4 is fluidly connected to port 1 of switching valve 64, and one end of sample loop 12 is fluidly connected to ports 3 and 6, respectively, of switching valve 64. Port 2 of switching valve 64 is in fluid communication with the common port of switching valve 66 via channel 68. Ports 4 and 5 of switching valve 64 are closed.

[0050] The sample supply flow path 26 leading to the injection section 2 is fluidly connected to port 2 of the switching valve 66, and the sample source flow path 52 is fluidly connected to port 4 of the switching valve 66. The pre-treatment unit 50 is provided on the sample source flow path 52. Port 5 of the switching valve 66 leads to a drain, and port 6 leads to a container that stores a washing solution. Ports 1 and 3 of the switching valve 66 are closed.

[0051] 15, in this online sampling system 1'', ports 1-6 and 2-3 of switching valve 64 are fluidly connected, and the common port of switching valve 66 is fluidly connected to port 4, thereby constructing a sample collection path that fluidly connects pump unit 4 and sample source flow path 52 with sample loop 12 interposed therebetween. In this state, by driving either syringe pump 28 or 30 of pump unit 4 for suction, the sample from the sample source can be drawn into sample loop 12.

[0052] 16, by fluidically connecting ports 1-6 and ports 2-3 of switching valve 64 and fluidically connecting the common port of switching valve 66 with port 2, a sample supply path is established in which pump unit 4 and sample supply channel 26 are fluidically connected with sample loop 12 interposed therebetween. In this state, by driving pump unit 4 so as to push the sample drawn into sample loop 12 toward sample supply channel 26, the sample held in sample loop 12 can be supplied to injection unit 2. At this time, by fluidically connecting ports 3-4 and ports 5-6 of injection valve 20 of injection unit 2 and accessing needle 22 to drain port 16, the sample supplied to injection unit 2 through sample supply channel 26 can be sent to sample loop 18.

[0053] Fig. 17 is a configuration diagram showing yet another embodiment of the online sampling system. In the embodiment described below, the same components as those in the online sampling system 1 described with reference to Figs. 1 to 10 are given the same reference numerals, and detailed description thereof will be omitted.

[0054] In the online sampling system 1''' of this embodiment, a path construction unit for constructing various fluid flow paths is realized using only one switching valve 70.

[0055] The switching valve 70 is a seven-port valve with a common port in the center and ports 1 to 6 arranged counterclockwise around the common port, and is configured to selectively connect the central port to any one of ports 1 to 6.

[0056] The pump flow path 36 leading to the pump section 4 is fluidly connected to a common port of the switching valve 70. The sample loop 12 is provided on the pump flow path 36. The sample supply flow path 26 leading to the injection section 2 is fluidly connected to port 2 of the switching valve 70, and the sample source flow path 52 is fluidly connected to port 4 of the switching valve 70. The pre-treatment unit 50 is provided on the sample source flow path 52, and performs pre-treatment such as filtering on the sample flowing through the sample source flow path 52. Port 5 of the switching valve 70 is connected to a drain, and port 6 is connected to a container that stores a cleaning solution. Ports 1 and 3 of the switching valve 70 are closed.

[0057] In this online sampling system 1''', as shown in Figure 18, by fluidly connecting the common port of the switching valve 70 with the port 4, a sample collection path is constructed that fluidly connects the pump unit 4 and the sample source flow path 52 with the sample loop 12 interposed therebetween. In this state, by driving either the syringe pump 28 or 30 of the pump unit 4 for suction, the sample from the sample source can be drawn into the sample loop 12.

[0058] 19, by fluidically connecting the common port of the switching valve 70 with port 2, a sample supply path is established in which the pump unit 4 and the sample supply channel 26 are fluidically connected with the sample loop 12 interposed therebetween. In this state, by driving the pump unit 4 so as to push the sample drawn into the sample loop 12 toward the sample supply channel 26, the sample held in the sample loop 12 can be supplied to the injection unit 2. At this time, by fluidically connecting ports 3 and 4 and ports 5 and 6 of the injection valve 20 of the injection unit 2 and accessing the needle 22 to the drain port 16, the sample supplied to the injection unit 2 through the sample supply channel 26 can be sent to the sample loop 18.

[0059] The embodiment described above is merely one example of an embodiment of the online sampling system according to the present invention. The embodiment of the online sampling system according to the present invention is as follows.

[0060] In one embodiment of the online sampling system of the present invention, there is provided an online sampling system for collecting a sample from a sample source and injecting it into a mobile phase flowing through an analytical flow path of a liquid chromatograph, the system comprising: an injection unit including a first sample loop for temporarily holding a sample and an injection valve for switching the first sample loop between a state where it is incorporated into the analysis flow path and a state where it is separated from the analysis flow path; a sample supply channel fluidly connected to the injection section for supplying a sample to the injection section; a pump unit for suctioning and discharging liquid; a second sample loop provided separately from the first sample loop; a sample source flow path leading to a sample source; a path construction unit including one or more switching valves, configured to be able to selectively construct a plurality of fluid flow paths in the online sampling system by switching the one or more switching valves; The path construction unit a sample collection path fluidly connecting the sample source flow path and the pump unit in a closed system with the second sample loop interposed therebetween, for drawing a sample from the sample source into the second sample loop by the pump unit; and a sample supply path for disconnecting the second sample loop from the sample source flow path while maintaining the sample source flow path in a closed system state, fluidly connecting the pump unit or a pump other than the pump unit to the sample supply flow path with the second sample loop interposed therebetween, and supplying the sample held in the second sample loop to the injection unit through the sample supply flow path by the pump unit or the other pump; The system is configured to be able to selectively configure the

[0061] In a first aspect of the above embodiment, one of the one or more switching valves has a first port and a second port, the sample supply flow path is arranged to fluidly connect between the first port of the one switching valve and one port of the injection valve, and the pump unit is fluidly connected to the second port of the one switching valve.

[0062] In a second aspect of the above embodiment, the other pump is provided for delivering a solvent, and when the path construction unit constructs the sample supply path, the other pump and the sample supply flow path are fluidly connected to each other with the second sample loop interposed therebetween, thereby allowing the sample held in the second sample loop to be supplied to the injection unit together with the solvent delivered by the other pump.

[0063] A specific example of the second aspect of the present invention is an online sampling system further comprising a container unit in which a container for storing a sample is set, the injection unit having a sampling flow path with a needle at its tip for accessing the container set in the container unit and aspirating and dispensing liquid from and into the container, and the sample supply flow path and the sampling flow path are configured to be fluidically connected, so that when the path construction unit constructs the sample supply path, the sample supply flow path is fluidly connected to the container and the sample and solvent supplied through the sample supply flow path can be stored in the container. This aspect enables automatic dilution of a sample collected from a sample source.

[0064] In the specific embodiment described above, in which sample dilution can be automatically performed, the sample supply flow path and the sampling flow path are constantly fluidly connected via the injection valve, and when the first sample loop is disconnected from the analysis flow path, the first sample loop is interposed between the sample supply flow path and the sampling flow path. The path construction unit may be configured to fluidly connect the pump unit to the sample supply flow path and selectively construct an aspiration / discharge path for the pump unit to aspiration and discharge liquid through the needle. In this embodiment, the pump unit can be used to aspirate a sample from a container through a needle and draw it into the first sample loop. This allows a series of sampling operations, including collection of a sample from a sample source, dilution of the collected sample, and injection of the diluted sample into an LC, to be performed online.

[0065] In a third aspect of the above embodiment, a pretreatment flow path having a pretreatment unit that pretreats the sample drawn from the sample source toward the second sample loop is provided between the second sample loop and the sample source flow path when the sample collection path is constructed, and the path construction unit is configured to fluidly connect the liquid delivery pump and the pretreatment flow path, and at the same time, to selectively construct a pretreatment unit washing path for supplying the solvent to the pretreatment unit by the separate pump by disconnecting the pretreatment flow path from the sample source flow path and connecting it to a drain. This aspect allows the pretreatment unit to be washed while the pretreatment flow path is disconnected from the sample source flow path.

[0066] The pretreatment unit may be a filter for removing substances unnecessary for analysis from the sample, or a redissolving device for redissolving the sample that has precipitated in the flow path.

[0067] In the third aspect, the path construction unit may be configured to interpose the second sample loop between the liquid feed pump and the pretreatment flow path when the pretreatment unit washing path is constructed, thereby enabling the pretreatment unit and the inside of the second sample loop to be washed simultaneously.

[0068] In a fourth aspect of the above embodiment, a control unit is further provided for controlling operations of the injecting unit, the pump unit, and the path construction unit, and also for controlling the operation of the other pump if the other pump is provided, The control unit a sampling step of constructing the sampling path and drawing and holding a sample from the sample source into the second sample loop; a sample supply step of constructing the sample supply path and supplying the sample held in the second sample loop to the injection part by the pump part or the other pump after the sample collection step is completed; After the sample supply step is completed, an injection step is performed in which the sample is injected into the mobile phase by incorporating the first sample loop holding the sample into the analysis flow path.

[0069] In a fifth aspect of the above embodiment, the device further includes a control unit for controlling operations of the injector, the pump unit, the other pump, and the path construction unit, The control unit a sampling step of constructing the sampling path and drawing and holding a sample from the sample source into the second sample loop; a sample dilution step of constructing the sample supply path after the sample collection step is completed, fluidly connecting the sample supply flow path with the sampling flow path to allow the needle to access the empty container, and supplying the sample held in the second sample loop together with the solvent to the container by the other pump, thereby diluting the sample in the container; a sample suction step in which, after the sample dilution step is completed, the pump unit is fluidly connected to the sample supply flow path while the first sample loop is interposed between the sample supply flow path and the sampling flow path to construct the suction and discharge path, and the diluted sample in the container is drawn into the first sample loop by the pump unit; After the sample aspiration step is completed, an injection step is performed in which the sample is injected into the mobile phase by incorporating the first sample loop holding the sample into the analysis flow path. [Explanation of symbols]

[0070] 1,1',1'',1''' Online Sampling System 2 Injection part 4 Pump section 6,8,10,32,34,56,58,64,66,70 Switching valve 12 Sample Loop (Second Sample Loop) 14 Container section 16 drain port 18 Sample Loop (1st Sample Loop) 20 injection port 22 Needle 24 Sampling channel 26 Sample supply channel 28,30 Syringe pump 36 Pump flow path 38,44,46,60,62,68 Flow path 40 Liquid transfer pump 42 Solvent supply channel 48 Pretreatment channel 50 Pre-treatment Unit 52 Sample source channel 54 Container

Claims

1. 1. An online sampling system for withdrawing a sample from a sample source and injecting it into a mobile phase flowing through an analytical flow path of a liquid chromatograph, comprising: an injection unit including a first sample loop for temporarily holding a sample and an injection valve for switching the first sample loop between a state where it is incorporated into the analysis flow path and a state where it is separated from the analysis flow path; a sample supply channel fluidly connected to the injection section for supplying a sample to the injection section; a pump unit for suctioning and discharging liquid; a second sample loop provided separately from the first sample loop; a sample source flow path leading to a sample source; a path construction unit including one or more switching valves, configured to be able to selectively construct a plurality of fluid flow paths in the online sampling system by switching the one or more switching valves; The path construction unit a sampling path fluidly connecting the sample source flow path and the pump unit in a closed system with the second sample loop interposed therebetween, for drawing a sample from the sample source into the second sample loop by the pump unit; and a sample supply path for disconnecting the second sample loop from the sample source flow path while maintaining the sample source flow path in a closed system state, fluidly connecting the pump unit or a pump other than the pump unit to the sample supply flow path with the second sample loop interposed therebetween, and supplying the sample held in the second sample loop to the injection unit through the sample supply flow path by the pump unit or the other pump; An online sampling system configured to selectively configure:

2. a switching valve of the one or more switching valves having a first port and a second port; the sample supply channel is provided to fluidly connect the first port of the one switching valve and one port of the injection valve; The online sampling system of claim 1 , wherein the pump section is fluidly connected to a second port of the one switching valve.

3. the other pump is provided for pumping a solvent; 2. The online sampling system of claim 1, wherein when the path construction unit constructs the sample supply path, the other pump and the sample supply flow path are fluidly connected to each other with the second sample loop interposed therebetween, thereby supplying the sample held in the second sample loop to the injection unit together with the solvent delivered by the other pump.

4. Further provided is a container portion in which a container for accommodating a sample is set, 4. The online sampling system of claim 3, wherein the injection unit is provided with a sampling flow path having a needle at its tip for accessing the container set in the container unit and aspirating liquid from the container and discharging liquid into the container, and is configured so that the sample supply flow path and the sampling flow path can be fluidly connected, thereby fluidly connecting the sample supply flow path to the container when the path construction unit constructs the sample supply path, and storing the sample and solvent supplied through the sample supply flow path in the container.

5. the sample supply flow path and the sampling flow path are always in fluid communication with each other via the injection valve, and when the first sample loop is separated from the analysis flow path, the first sample loop is interposed between the sample supply flow path and the sampling flow path; 5. The online sampling system of claim 4, wherein the path construction unit is configured to fluidly connect the pump unit to the sample supply flow path and selectively construct an aspiration and discharge path for the pump unit to aspire and discharge liquid through the needle.

6. a pretreatment flow path having a pretreatment unit for pretreatment of the sample drawn from the sample source toward the second sample loop is provided so as to be interposed between the second sample loop and the sample source flow path when the sample collection path is constructed; The online sampling system of claim 1, wherein the path construction unit is configured to fluidly connect the pump unit and the pretreatment flow path, and at the same time, to selectively construct a pretreatment unit washing path for supplying a solvent to the pretreatment unit by the separate pump by disconnecting the pretreatment flow path from the sample source flow path and connecting it to a drain.

7. 7. The online sampling system according to claim 6, wherein the pretreatment unit is a filter for removing substances unnecessary for analysis from the sample, or a redissolving device for redissolving the sample precipitated in the flow path.

8. 8. The online sampling system of claim 6, wherein the path construction unit is configured to interpose the second sample loop between the pump unit and the pretreatment flow path when the pretreatment unit cleaning path is constructed.

9. a control unit for controlling the operations of the injection unit, the pump unit, and the path construction unit, and also for controlling the operation of the other pump if the other pump is provided; The control unit a sampling step of constructing the sampling path and drawing and holding a sample from the sample source into the second sample loop; a sample supply step of constructing the sample supply path and supplying the sample held in the second sample loop to the injection part by the pump part or the other pump after the sample collection step is completed; 3. The online sampling system of claim 1, further comprising: an injection step of injecting the sample into the mobile phase by incorporating the first sample loop holding the sample into the analytical flow path after the sample supply step is completed.

10. a control unit for controlling operations of the injecting unit, the pump unit, the other pump, and the path construction unit; The control unit a sampling step of constructing the sampling path and drawing and holding a sample from the sample source into the second sample loop; a sample dilution step of constructing the sample supply path after the sample collection step is completed, fluidly connecting the sample supply flow path with the sampling flow path to allow the needle to access the empty container, and supplying the sample held in the second sample loop together with the solvent to the container by the other pump, thereby diluting the sample in the container; a sample suction step in which, after the sample dilution step is completed, the pump unit is fluidly connected to the sample supply flow path while the first sample loop is interposed between the sample supply flow path and the sampling flow path to construct the suction and discharge path, and the diluted sample in the container is drawn into the first sample loop by the pump unit; 6. The online sampling system of claim 5, further comprising: an injection step of injecting the sample into the mobile phase by incorporating the first sample loop holding the sample into the analytical flow path after the sample aspiration step is completed.

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