Preparative liquid chromatograph

Abstract

A preparative liquid chromatograph includes a flow path switching valve connected to a feed pump, a separation column connected to the flow path switching valve, a detector connected to the separation column at one end and to the flow path switching valve at the other end, and a suction ejection device connected to the flow path switching valve at both ends. The flow path switching valve is capable of switching between a first switching state in which the suction ejection device is connected downstream of the feed pump and the separation column is connected downstream of the suction ejection device, and a second switching state in which the separation column is connected downstream of the feed pump and the suction ejection device is connected downstream of the detector. In the first switching state, the suction ejection device functions as a sample injection device, and in the second switching state, the suction ejection device functions as a dispensing device.

Description

Technical Field

[0001] This invention relates to a preparative liquid chromatograph for recovering eluent from a separation column. Background Technology

[0002] A liquid chromatograph is known as an instrument for analyzing components contained in a sample. A liquid chromatograph includes a pump, a sample injection device, a separation column, and a detector. Furthermore, a preparative liquid chromatograph is known that dispenses the eluent containing components separated in the separation column into multiple recovery containers. An automated dispensing device for dispensing the eluent is used in preparative liquid chromatographs. A preparative liquid chromatograph for extracting target components is disclosed in Patent Document 1 below.

[0003] Patent Document 1: Japanese Patent Application Publication No. 2016-38389 Summary of the Invention

[0004] The problem the invention aims to solve

[0005] In preparative liquid chromatographs (HPLC), a sample injection device is used in the step of injecting the sample into the mobile phase. An automated dispensing device is also used in the step of dispensing the eluent containing the target component. Therefore, preparative HPLC requires both a sample injection device and an automated dispensing device, increasing the number of components and thus raising the overall cost.

[0006] The purpose of this invention is to reduce the number of components in a preparative liquid chromatograph and to reduce the cost of the apparatus.

[0007] Solution for solving the problem

[0008] A preparative liquid chromatograph according to one aspect of the present invention includes: a delivery pump; a flow path switching valve connected to the delivery pump; a separation column connected to the flow path switching valve; a detector connected at one end to the separation column and at the other end to the flow path switching valve; and a suction-ejection device connected at both ends to the flow path switching valve. The flow path switching valve is switchable between a first switching state and a second switching state. In the first switching state, the flow path is switched such that the suction-ejection device is connected downstream of the delivery pump and the separation column is connected downstream of the suction-ejection device. In the second switching state, the flow path is switched such that the separation column is connected downstream of the delivery pump and the suction-ejection device is connected downstream of the detector. In the first switching state, the suction-ejection device functions as a sample injection device, and in the second switching state, the suction-ejection device functions as a dispensing device.

[0009] The effects of the invention

[0010] According to the present invention, the number of components in a preparative liquid chromatograph can be reduced and the cost of the apparatus can be lowered. Attached Figure Description

[0011] Figure 1 This is an overall diagram of the preparative liquid chromatograph of this embodiment.

[0012] Figure 2 This is a diagram showing the suction and ejection device of this embodiment.

[0013] Figure 3 This is a diagram showing a preparative liquid chromatograph performing a sample injection process.

[0014] Figure 4 This diagram shows a suction and ejection device that operates as a sample injection device.

[0015] Figure 5 This diagram shows a suction and ejection device that operates as a sample injection device.

[0016] Figure 6 This diagram shows a suction and ejection device that operates as a sample injection device.

[0017] Figure 7 This is a diagram showing a preparative liquid chromatograph performing a dispensing process.

[0018] Figure 8 This diagram shows a suction and ejection device that operates as an automatic dispensing unit.

[0019] Figure 9 This diagram shows a suction and ejection device that operates as an automatic dispensing unit. Detailed Implementation

[0020] Next, a preparative liquid chromatograph according to an embodiment of the present invention will be described with reference to the accompanying drawings.

[0021] (1) Structure of a preparative liquid chromatograph

[0022] Figure 1 This is a diagram illustrating the structure of the preparative liquid chromatograph 10 according to an embodiment of the present invention. (See diagram below.) Figure 1 As shown, in this embodiment, the preparative liquid chromatograph 10 includes a first solvent supply unit 1A, a second solvent supply unit 1B, a mixing unit 2, a suction and ejection device 3, a separation column 4, a detector 5, and a high-pressure flow path switching valve 6. The first solvent supply unit 1A includes a first solvent container 11A and a first delivery pump 12A. The second solvent supply unit 1B includes a second solvent container 11B and a second delivery pump 12B. The high-pressure flow path switching valve 6 is an example of the flow path switching valve of the present invention.

[0023] The first solvent container 11A stores an aqueous or organic solvent used as the mobile phase. The first delivery pump 12A pressurizes and delivers the solvent stored in the first solvent container 11A to the flow path. The second solvent container 11B stores an aqueous or organic solvent used as the mobile phase. The second delivery pump 12B pressurizes and delivers the solvent stored in the second solvent container 11B to the flow path.

[0024] A mixing unit 2 is connected downstream of the first liquid delivery pump 12A and downstream of the second liquid delivery pump 12B. The mixing unit 2 generates various solvents (mobile phases) by mixing the solvent pressurized and delivered by the first liquid delivery pump 12A and the solvent pressurized and delivered by the second liquid delivery pump 12B in any proportion.

[0025] A flow path L1 is connected downstream of the mixing section 2. A high-pressure flow path switching valve 6 is connected downstream of the flow path L1. The flow path L1 is connected to the first port P1 of the high-pressure flow path switching valve 6. The high-pressure flow path switching valve 6 is a two-position six-way valve. The high-pressure flow path switching valve 6 can switch between a first switching state and a second switching state. In the first switching state, the first port P1 and the second port P2 are connected, the third port P3 and the fourth port P4 are connected, and the fifth port P5 and the sixth port P6 are connected. In the second switching state, the first port P1 and the sixth port P6 are connected, the second port P2 and the third port P3 are connected, and the fourth port P4 and the fifth port P5 are connected. Figure 1 This indicates the second switching state.

[0026] A flow path L2 is connected to port P2 of the high-pressure flow path switching valve 6. A suction ejection device 3 is connected to the downstream end of flow path L2. The structure of the suction ejection device 3 will be described in detail below. A flow path L5 is connected to the downstream side of the suction ejection device 3. Port P5 of the high-pressure flow path switching valve 6 is connected to the downstream end of flow path L5.

[0027] A flow path L6 is connected to port P6 of the high-pressure flow path switching valve 6. A separation column 4 is connected downstream of flow path L6. A mobile phase and a sample are supplied to the separation column 4. The target components contained in the sample are separated in the separation column 4. The separation column 4 is housed in a column oven (not shown). The column oven is used to maintain the separation column 4 at the temperature set in the analytical method.

[0028] A detector 5 is connected to the downstream side of the separation column 4 via a flow path. The detector 5 detects the sample after component separation in the separation column 4. For example, a UV-Vis spectrophotometer, a diode array detector, or a differential refractive index detector can be used as the detector 5.

[0029] A flow path L3 is connected downstream of detector 5. The third port P3 of a high-pressure flow path switching valve 6 is connected downstream of flow path L3. Furthermore, an outlet D is connected to the fourth port P4 of the high-pressure flow path switching valve 6.

[0030] (2) Structure of the suction and ejection device

[0031] Next, refer to Figure 2 Explain the structure of the suction and ejection device 3. Figure 2 This diagram illustrates the structure of the suction and ejection device 3. The suction and ejection device 3 includes a high-pressure flow path switching valve 31, a needle 32, an injection port 33, and a metering pump 34. In this embodiment, the suction and ejection device 3 operates as a sample injection device in the sample injection process and as an automatic dispensing device in the dispensing process.

[0032] The high-pressure flow path switching valve 31 is a two-position six-way valve. The high-pressure flow path switching valve 31 can switch between a first switching state and a second switching state. In the first switching state, port 1 S1 and port 2 S2 are connected and port 5 S5 and port 6 S6 are connected. In the second switching state, port 1 S1 and port 6 S6 are connected and port 4 S4 and port 5 S5 are connected. Figure 2 This indicates the second switching state.

[0033] like Figure 2 As shown, flow path M1 is connected to port S1. A needle 32 is connected to the downstream end of flow path M1. Flow path M2 is connected to port S2. A metering pump 34 is connected to the other end of flow path M2. Flow path M4 is connected to port S4. An injection port 33 is connected to the upstream end of flow path M4. Flow path L5 is connected to port S5 of the high-pressure flow path switching valve 31. Figure 1 As shown, the other end of flow path L5 is connected to port P5 of the high-pressure flow path switching valve 6. Flow path L2 is connected to port S6 of the high-pressure flow path switching valve 31. Figure 1 As shown, the other end of flow path L2 is connected to port P2 of high-pressure flow path switching valve 6.

[0034] (3) Operation of a preparative liquid chromatograph

[0035] Next, refer to Figures 3-9 Explain the operation of the preparative liquid chromatograph 10. Figures 3-6 This is a diagram showing the state of the preparative liquid chromatograph 10 performing the sample injection process. Figures 7-9 This is a diagram showing the state of the preparative liquid chromatograph 10 performing the dispensing process.

[0036] {3-1 Sample Injection Procedure}

[0037] The sample injection process is divided into three steps, J1 to J3, for explanation. When the preparative liquid chromatograph 10 performs the sample injection process, the suction and ejection device 3 functions as the sample injection device (autosampler). For example... Figure 3 As shown, firstly, before step J1, the first liquid delivery pump 12A is driven to pressurize and deliver the mobile phase stored in the first solvent container 11A to the flow path. Furthermore, the second liquid delivery pump 12B is driven to pressurize and deliver the mobile phase stored in the second solvent container 11B to the flow path.

[0038] The mobile phase, pressurized and delivered by the first delivery pump 12A and the second delivery pump 12B, is mixed in the mixing section 2 at a set mixing ratio. The mixed mobile phase in the mixing section 2 flows through the flow path L1 into the high-pressure flow path switching valve 6. (Example...) Figure 3 As shown, during the sample injection process, the high-pressure flow path switching valve 6 is in the first switching state. In this first switching state, port 1 P1 and port 2 P2 are connected, port 3 P3 and port 4 P4 are connected, and port 5 P5 and port 6 P6 are connected. This allows the mobile phase flowing into port 1 P1 to flow into flow path L2 via port 2 P2.

[0039] Figure 4 This is a diagram showing the suction and ejection device 3 in step J1 of the sample injection process. Figure 4 In the J1 process shown, the high-pressure flow path switching valve 31 is in a first switching state where ports S1 and S2 are connected and ports S5 and S6 are connected. Furthermore, in the J1 process, the needle 32 moves into the sample container 35. In this state, the metering pump 34 is driven to draw the sample from the tip of the needle 32 into the sample container 35. The drawn-out sample is held in the flow path M1. Although not shown in the diagram, a sample loop is provided in the flow path M1, and the drawn-out sample is held using the tubing of the flow path M1 and the sample loop. Figure 4 In the diagram, the black-painted portion in flow path M1 indicates the presence of a sample. For example... Figure 4 As shown, in process J1, the mobile phase flowing in flow path L2 flows into flow path L5 via port 6 S6 and port 5 S5. For example... Figure 3 As shown, the mobile phase flowing in flow path L5 flows into flow path L3 via separation column 4 and detector 5. The mobile phase flowing in flow path L3 is then discharged from outlet D via port 3 P3 and port 4 P4.

[0040] exist Figure 5 In step J2 of the sample injection process shown, the high-pressure flow path switching valve 31 is also in the first switching state. Furthermore, in step J2, the needle 32 moves into the injection port 33. At this time, the sample is held within the flow path M1. Figure 5In the diagram, the black-painted portion in flow path M1 indicates the presence of a sample. In step J2, the mobile phase flowing in flow paths L2 and L5 is discharged from outlet D via separation column 4 and detector 5.

[0041] exist Figure 6 In step J3 of the sample injection process shown, the high-pressure flow path switching valve 31 is in a second switching state, connecting ports S1 and S6 and ports S4 and S5. In step J3, by switching the high-pressure flow path switching valve 31 to the second switching state, the flow path M1 holding the sample is incorporated into the analytical flow path leading to the separation column 4. Thus, the aspiration ejection device 3 of this embodiment operates as a sample injection device in a full-volume injection mode. By incorporating the flow path M1 into the analytical flow path, the sample held in the flow path M1 is ejected from the tip of the needle 32 and flows into the flow path M4 via the injection port 33. Figure 6 In the diagram, the black-painted portion in flow path M4 indicates the state of sample introduction into the analytical flow path. In step J3, the mobile phase containing the sample flows into flow path L5 via ports S4 and S5. (Example...) Figure 3 As shown, the sample and mobile phase flowing in flow path L5 enter flow path L6 via ports P5 (5th port) and P6 (6th port) of the high-pressure flow path switching valve 6. Figure 3 In the diagram, the black-painted portions in flow paths L5 and L6 indicate the state of the sample being introduced into the analytical flow path during step J3.

[0042] In process J3, such as Figure 3 As shown, the sample and mobile phase flowing in flow path L6 are supplied to separation column 4. During passage through separation column 4, the components contained in the sample are separated. The component-separated sample, along with the mobile phase, is supplied as eluent to detector 5. The components contained in the sample are detected in detector 5. The eluent (mobile phase and component-separated sample) flowing out of detector 5 is discharged from outlet D via flow path L3, port 3 P3, and port 4 P4. The sample injection process (processes J1 to J3) is performed as described above.

[0043] {3-2 Packaging Process}

[0044] The dispensing process is divided into two steps, F1 and F2. When the preparative liquid chromatograph 10 performs the dispensing process, the suction-ejection device 3 operates as an automatic dispensing device. For example... Figure 7As shown, in the dispensing process, the high-pressure flow path switching valve 6 enters the second switching state. In this second switching state, port 1 P1 and port 6 P6 are connected, port 2 P2 and port 3 P3 are connected, and port 4 P4 and port 5 P5 are connected. For example, during the sample injection process, when the sample is injected by the suction ejection device 3, the high-pressure flow path switching valve 6 switches from the first switching state to the second switching state. Thus, the eluent (mobile phase and the component-separated sample) eluted from the separation column 4 flows into flow path L2 via detector 5, flow path L3, port 3 P3, and port 2 P2. Figure 7 In the diagram, the black-painted portions in flow paths L3 and L2 represent the eluent eluted from separation column 4 during process F1.

[0045] Figure 8 This is a diagram showing the suction and ejection device 3 in process F1 of the packaging process. Figure 8 In the F1 process shown, the high-pressure flow path switching valve 31 is in a first switching state where ports S1 and S2 are connected and ports S5 and S6 are connected. Furthermore, in the F1 process, needle 32 moves into the recovery container 36. In the F1 process, the eluent (mobile phase and the component-separated sample) flowing in through flow path L2 flows into flow path L5 via ports S6 and S5. Figure 7 As shown, the eluent flowing in flow path L5 is discharged from outlet D via port 5 P5 and port 4 P4.

[0046] exist Figure 9 In step F2 of the dispensing process shown, the high-pressure flow path switching valve 31 is in a second switching state where port 1 S1 and port 6 S6 are connected, and port 4 S4 and port 5 S5 are connected. In the dispensing process, as... Figure 7 As shown, the eluent flowing in flow path L3 is supplied to the suction and ejection device 3, which operates as an automatic dispensing device, via port 3 P3, port 2 P2, and flow path L2. Figure 9 As shown, the eluent supplied via flow path L2 is recovered by recovery container 36 via port 6 S6, port 1 S1, and flow path M1. Thus, the eluent eluted from separation column 4 (mobile phase and component-separated sample) is recovered in recovery container 36. Figure 9 In the diagram, the black-painted portion in flow path M1 represents the eluent flowing toward recovery container 36. By switching between multiple recovery containers 36 under the control of a control device (not shown), the eluent of the sample that has undergone component separation in the time direction is recovered in multiple recovery containers 36.

[0047] As explained above, the preparative liquid chromatograph 10 of this embodiment can operate the suction-ejection device 3 as either a sample injection device or an automatic dispensing device. Therefore, the preparative liquid chromatograph 10 of this embodiment can reduce the number of components in the apparatus and reduce the cost of the apparatus. When the high-pressure flow path switching valve 6 is switched to the first switching state to perform the sample injection process, and when the high-pressure flow path switching valve 6 is switched to the second switching state to perform the dispensing process, in either case, the flow path L2 is upstream of the suction-ejection device 3, and the flow path L5 is downstream of the suction-ejection device 3. With such a device structure, a single suction-ejection device 3 can operate as either a sample injection device or an automatic dispensing device.

[0048] As described above, the suction and ejection device 3 of this embodiment operates as a sample injection device for full-volume injection. That is, it is a structure in which the needle 32 is integrated into the analytical flow path. Therefore, during the dispensing process, the needle 32 can be used to directly eject the sample into a septum-equipped sample vial.

[0049] Furthermore, many sample injection devices are equipped with a cooling function for the stable preservation of samples. Therefore, when the suction and ejection device 3 operates as an automatic dispensing device, the cooling function of the sample injection device can be utilized. This cooling function allows for the stable preservation of the eluent recovered by the automatic dispensing device.

[0050] Previously, because the sample injection device and the automatic dispensing device were separate devices, the eluent recovered by the automatic dispensing device could not be re-dispensed. According to this embodiment, since the suction ejection device 3 operates as both the sample injection device and the automatic dispensing device, the recovered eluent can be injected into the analytical flow path, thereby providing a new analytical method.

[0051] (4) Other implementation methods

[0052] In the above embodiments, the example described is that the suction and ejection device 3 operates as an automatic dispensing device in the dispensing process. In other embodiments, the suction and ejection device 3 can also operate as a manual dispensing device. In this case, the needle 32 is moved into the recovery container 36 by the operator. The operator only needs to replace the recovery container 36 according to the elution timing of each separated component.

[0053] In the above-described embodiment, the preparative liquid chromatograph 10 includes a mixing unit 2. Therefore, the preparative liquid chromatograph 10 can perform gradient analysis, etc. Alternatively, the preparative liquid chromatograph 10 may be configured to have only a solvent supply unit and lack the mixing unit 2.

[0054] As constituent elements of the claims, various elements having the structure or function described in the claims can also be used.

[0055] (5) Technical solution

[0056] Those skilled in the art will understand that the above-described embodiments are specific examples of the following technical solutions.

[0057] (Item 1)

[0058] A preparative liquid chromatograph according to one embodiment of the present invention includes:

[0059] Liquid delivery pump;

[0060] A flow path switching valve, which is connected to the liquid delivery pump;

[0061] A separation column, which is connected to the flow path switching valve;

[0062] The detector, one end of which is connected to the separation column and the other end of which is connected to the flow path switching valve; and

[0063] The suction and ejection device has its two ends connected to the flow path switching valve.

[0064] The flow path switching valve can switch between a first switching state and a second switching state. In the first switching state, the flow path is switched so that the suction and ejection device is connected downstream of the liquid delivery pump and the separation column is connected downstream of the suction and ejection device. In the second switching state, the flow path is switched so that the separation column is connected downstream of the liquid delivery pump and the suction and ejection device is connected downstream of the detector. In the first switching state, the suction and ejection device functions as a sample injection device. In the second switching state, the suction and ejection device functions as a dispensing device.

[0065] This can reduce the number of components in a preparative liquid chromatograph and reduce the cost of the equipment.

[0066] (Item 2)

[0067] In the preparative liquid chromatograph described in item 1, it can also be,

[0068] The sample injection process is performed using the suction and ejection device, which operates as the sample injection device in the first switching state. After the sample injection process, the flow path switching valve switches to the second switching state to perform the dispensing process.

[0069] By switching the flow path valve, the suction and ejection device can be used as both a sample injection device and a dispensing device.

[0070] (Item 3)

[0071] In the preparative liquid chromatograph described in item 1 or item 2, it may also be,

[0072] The suction and ejection device includes a needle for suctioning or ejecting samples.

[0073] When the suction and ejection device operates as the sample injection device, the needle draws the sample from the sample container. When the suction and ejection device operates as the dispensing device, the needle ejects the eluent flowing from the separation column into the recovery container.

[0074] The needles of the suction and ejection device can be used in the sample injection and dispensing processes.

[0075] (Item 4)

[0076] In any of the preparative liquid chromatographs described in items 1 to 3, it may also be,

[0077] In the first switching state, a discharge port is connected downstream of the detector via the flow path switching valve.

[0078] In the first switching state, the eluent flowing out of the separation column can be discharged from the outlet.

[0079] (Item 5)

[0080] In the preparative liquid chromatograph described in item 4, it can also be,

[0081] The suction and ejection device functions as a sample injection device for the full-volume injection method.

[0082] It can effectively utilize the sample.

[0083] (Item 6)

[0084] In any of the preparative liquid chromatographs described in items 1 to 3, it may also be,

[0085] In the second switching state, a discharge port is connected downstream of the suction and ejection device via the flow path switching valve.

[0086] In the second switching state, the eluent flowing out of the separation column can be discharged from the outlet.

Claims

1. A preparative liquid chromatograph, wherein, This preparative liquid chromatograph includes: Liquid delivery pump; A flow path switching valve, which is connected to the liquid delivery pump; A separation column, which is connected to the flow path switching valve; The detector, one end of which is connected to the separation column and the other end of which is connected to the flow path switching valve; and The suction and ejection device has its two ends connected to the flow path switching valve. The flow path switching valve can switch between a first switching state and a second switching state. In the first switching state, the flow path is switched so that the suction and ejection device is connected downstream of the liquid delivery pump and the separation column is connected downstream of the suction and ejection device. In the second switching state, the flow path is switched so that the separation column is connected downstream of the liquid delivery pump and the suction and ejection device is connected downstream of the detector. In the first switching state, the suction and ejection device operates as a sample injection device. In the second switching state, the suction and ejection device operates as a dispensing device. When the sample is injected by the suction and ejection device, which operates as the sample injection device, the flow path switching valve switches from the first switching state to the second switching state.

2. The preparative liquid chromatograph according to claim 1, wherein, The sample injection process is performed using the suction and ejection device, which operates as the sample injection device in the first switching state. After the sample injection process, the flow path switching valve switches to the second switching state to perform the dispensing process.

3. The preparative liquid chromatograph according to claim 1 or 2, wherein, The suction and ejection device includes a needle for suctioning or ejecting the sample. When the suction and ejection device operates as the sample injection device, the needle draws the sample from the sample container. When the suction and ejection device operates as the dispensing device, the needle ejects the eluent flowing from the separation column into the recovery container.

4. The preparative liquid chromatograph according to claim 1 or 2, wherein, In the first switching state, a discharge port is connected downstream of the detector via the flow path switching valve.

5. The preparative liquid chromatograph according to claim 4, wherein, The suction and ejection device functions as a sample injection device for the full-volume injection method.

6. The preparative liquid chromatograph according to claim 1 or 2, wherein, In the second switching state, a discharge port is connected downstream of the suction and ejection device via the flow path switching valve.

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