Fractionation Systems

Abstract

This first movement phase is supplied by a movement phase supply unit. A sample is provided by a sample supply unit to the first movement phase supplied by the movement phase supply unit. The sample supplied by the sample supply unit passes through a separation column. The sample that has passed through the separation column is detected by a detector. A component of the sample that has passed through the separation column is captured by a trap column on the basis of a detection result from the detector. A liquid feeding unit supplies a make-up solution to the detector, and supplies an eluting solution for eluting the sample to the trap column.

Description

[Technical field]

[0001] The present invention relates to a fraction collection system. [Background technology]

[0002] There is known a preparative separation system that separates a sample into components by LC (liquid chromatograph) and collects the separated components of the sample by fractionation. For example, in the liquid chromatography preparative separation system described in Patent Document 1, a sample injected into an analysis flow path is transferred to a separation column by a mobile phase. The separated components of the sample are eluted from the separation column and detected by a detector. Based on a signal from the detector in the analysis flow path, an eluate containing the desired target component is collected by a sample loop.

[0003] After the target components have been collected in the sample loop, a solvent is supplied to the sample loop. This introduces the collected target components into the second-dimensional flow path and they are detected by a detector. Based on the signal from the detector in the second-dimensional flow path, the target components are fractionated and collected in a designated container by a fraction collector.

[0004] Also, a mass spectrometer (MS) may be used as a detector for detecting the eluent eluted from the separation column. For example, in a preparative LCMS system described in Patent Document 2, a part of the eluent from the separation column is introduced into the MS together with the mobile phase delivered by a makeup pump. Based on a detection signal from the MS, the eluent from the separation column is fractionated and collected in a predetermined container by a fraction collector.

[0005] [Patent Document 1] International Publication No. 2020 / 080041 [Patent Document 2] JP 2005-241580 A Summary of the Invention [Problem to be solved by the invention]

[0006] In a preparative separation system, it is sometimes required to provide an MS as a detector for the analysis flow path. However, if the MS of Patent Document 2 is provided in the liquid chromatography preparative separation system of Patent Document 1, a make-up pump must be added. This increases the size and cost of the liquid chromatography preparative separation system.

[0007] An object of the present invention is to provide a fraction collection system which is prevented from becoming large and expensive. [Means for solving the problem]

[0008] One aspect of the present invention relates to a separation system comprising: a mobile phase supplying unit that supplies a first mobile phase; a first sample supplying unit that supplies a sample to the first mobile phase supplied by the mobile phase supplying unit; a first separation column through which the sample supplied by the first sample supplying unit passes; a first detector that detects the sample that has passed through the first separation column; a trap column that collects components of the sample that has passed through the first separation column based on the detection result by the first detector; and a liquid delivery unit that supplies a make-up solution to the first detector and supplies an eluent that elutes the sample to the trap column. Effect of the Invention

[0009] According to the present invention, it is possible to prevent the size and cost of a collection system from increasing. [Brief description of the drawings]

[0010] [Figure 1] FIG. 1 is a diagram showing the configuration of a fraction collection system according to a first embodiment of the present invention. [Diagram 2] FIG. 2 is a diagram for explaining the first dimensional operation of the fraction collection system of FIG. [Diagram 3] FIG. 3 is a diagram for explaining the second dimensional operation of the fraction collection system of FIG. [Figure 4] FIG. 4 is a diagram showing the configuration of a fraction collection system according to a reference example. [Diagram 5] FIG. 5 is a diagram showing the configuration of a fraction collection system according to the second embodiment. [Figure 6] FIG. 6 is a plan view showing an example of a tray provided in the liquid handler. [Figure 7] FIG. 7 is a diagram for explaining the second dimensional operation of the fraction collection system of FIG. [Figure 8] FIG. 8 is a diagram for explaining the operation of the fraction collection system of FIG. 5 during analysis. [Figure 9] FIG. 9 is a diagram showing the configuration of a fraction collection system in the first modified example. [Figure 10] FIG. 10 is a diagram showing the configuration of a fraction collection system according to the third embodiment. [Figure 11] FIG. 11 is a diagram for explaining the first dimensional operation of the fraction collection system of FIG. [Figure 12] FIG. 12 is a diagram for explaining the operation of the fraction collection system of FIG. 10 during analysis. [Figure 13] FIG. 13 is a diagram showing the configuration of a fraction collection system in the second modified example. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] <1> First embodiment (1) Configuration of the fractionation system Hereinafter, a collection system according to an embodiment of the present invention will be described in detail with reference to the drawings. Fig. 1 is a diagram showing the configuration of a collection system according to a first embodiment of the present invention. As shown in Fig. 1, the collection system 100 includes a control unit 110, a separation unit 120, a detector 130, a collection unit 140, a dilution unit 150, and a recovery unit 160. The collection system 100 also includes a plurality of flow path switching units 10, 20, 30, and 40 that appropriately connect the separation unit 120, the detector 130, the collection unit 140, the dilution unit 150, and the recovery unit 160.

[0012] The control unit 110 includes, for example, a CPU (Central Processing Unit) and a memory, or a microcomputer, etc. The control unit 110 controls the operation of each part of the fraction collection system 100 based on the predetermined detection results in the separation unit 120, the detector 130, or the collection unit 160. The control unit 110 also performs data processing such as chromatogram generation based on the predetermined detection results in the separation unit 120, the detector 130, or the collection unit 160.

[0013] The separation unit 120 is, for example, a liquid chromatograph (LC), and includes a mobile phase supply unit 121, a sample supply unit 122, a separation column 123, and a detector 124. In this example, the mobile phase supply unit 121 includes two liquid delivery pumps and a gradient mixer (not shown), and performs gradient delivery of the mobile phase. The sample supply unit 122 is provided in, for example, a liquid handler, and introduces the sample to be analyzed into the separation column 123 together with the mobile phase supplied by the mobile phase supply unit 121.

[0014] The separation column 123 is housed inside a column thermostatic bath (not shown) and separates the introduced sample into components based on differences in chemical properties or composition. The detector 124 is, for example, a PDA (photodiode array) or a UV (ultraviolet) detector. The flow path downstream of the separation column 123 branches into two. The detector 124 is provided in one of the flow paths downstream of the separation column 123 and detects the components of the sample separated by the separation column 123.

[0015] The detector 130 is Separation column 123 The detector 130 is provided in the other flow path downstream of the detector 130. In this example, the detector 130 is a mass spectrometer, and detects components of the sample by performing mass analysis of the ionized sample. A make-up solution is introduced into the detector 130 together with the sample to improve the transport efficiency of the sample, the ionization efficiency of the sample, or the sensitivity of the detector 130.

[0016] Collection section 140 includes a plurality of collection channels 141, a bypass channel 142, channel switching sections 143 and 144, and a trap column 145. A plurality of (five in this example) collection channels 141 and bypass channels 142 connect in parallel between channel switching section 143 and channel switching section 144. Channel switching sections 143 and 144 are, for example, multi-way switching valves, and selectively switch the channel between channel switching sections 143 and 144 to either the plurality of collection channels 141 or the bypass channel 142. A plurality of trap columns 145 are provided in the plurality of collection channels 141, respectively, and adsorb and collect components of a sample introduced into the corresponding collection channels 141.

[0017] The dilution section 150 includes a diluent generating section 151 and a liquid sending section 152. The diluent generating section 151 generates a diluent for improving the efficiency of sample collection in the trap column 145 in the collection section 140. The liquid sending section 152 is, for example, a liquid sending pump, and pressure-feeds the diluent generated by the diluent generating section 151 to each trap column 145.

[0018] The collection unit 160 includes a liquid delivery unit 161, a detector 162, and a fraction collector 163. The liquid delivery unit 161 is, for example, a liquid delivery pump, and pumps the make-up solution to the detector 130 during a first dimension operation described below. The detector 162 pumps an eluent to the collection unit 140 for extracting the components of the sample trapped in the trap column 145 of the collection unit 140 during a second dimension operation described below. The detector 162 is, for example, a PDA or UV detector, and detects the components of the sample extracted from the trap column 145. The fraction collector 163 collects the components of the sample detected by the detector 162 in a predetermined container (a test tube in this example).

[0019] The flow path switching units 10, 20, 30, 40 are, for example, multi-way switching valves. The flow path switching unit 10 has six ports 11 to 16, and can be switched between a first connection state and a second connection state. In the first connection state, ports 11 and 12 are connected, ports 13 and 14 are connected, and ports 15 and 16 are connected. In the second connection state, ports 12 and 13 are connected, ports 14 and 15 are connected, and ports 16 and 11 are connected.

[0020] The flow path switching unit 20 has six ports 21-26. The flow path switching unit 30 has six ports 31-36. The configuration of each of the flow path switching units 20, 30 is similar to the configuration of the flow path switching unit 10. Therefore, each of the flow path switching units 20, 30 can be switched between a first connection state and a second connection state. The flow path switching unit 40 has seven ports 41-47. The port 47 is selectively connected to any one of the ports 41-46.

[0021] In the flow path switching unit 10, port 11 is connected to a waste liquid unit (drain) not shown. Port 13 is connected to port 23 of the flow path switching unit 20. Port 14 is connected to a downstream end of the detector 124 of the separation unit 120. Port 15 is connected to a fraction collector 163 of the collection unit 160. Port 16 is connected to a downstream end of the detector 162 of the collection unit 160.

[0022] In the flow path switching unit 20, the port 21 is connected to the upstream end of the detector 162 of the recovery unit 160. The port 22 is connected to the port 34 of the flow path switching unit 30. The port 23 is connected to the port 13 of the flow path switching unit 10 as described above. The port 24 is connected to the waste liquid unit. The port 25 is connected to the flow path switching unit 144 of the collection unit 140. The port 26 is connected to the port 45 of the flow path switching unit 40.

[0023] In the flow path switching unit 30, the port 31 is connected to the liquid delivery unit 152 of the dilution unit 150. The ports 32 and 33 are connected to the waste liquid unit. The port 34 is connected to the port 22 of the flow path switching unit 20 as described above. The port 35 is connected to the flow path switching unit 143 of the collection unit 140. The port 36 is connected to each trap column 145 of the collection unit 140.

[0024] In the flow path switching unit 40, the port 41 is connected to a waste liquid section. Upstream The port 45 is connected to the port 26 of the flow path switching unit 20 as described above. The port 47 is connected to the liquid delivery unit 161 of the recovery unit 160. In this embodiment, the ports 42, 43, and 46 are not connected to any of them.

[0025] (2) Operation of the fractionation system The fraction collection system 100 selectively executes a first dimension operation and a second dimension operation. FIG. 2 is a diagram for explaining the first dimension operation of the fraction collection system 100 of FIG. 1. As shown in FIG. 2, during the first dimension operation, the flow path switching unit 10 is in a first connection state, and each of the flow path switching units 20 and 30 is in a second connection state. In the flow path switching unit 40, the port 44 and the port 47 are connected. As a result, the flow path shown by the thick solid line in FIG. 2 is formed.

[0026] In the first dimension operation, a mobile phase is supplied by a mobile phase supplying unit 121 in the separation unit 120. In addition, a sample to be analyzed is collected by a sample supplying unit 122 from an arbitrary vial held on a tray (not shown) and supplied to the flow path of the separation unit 120. The supplied sample is introduced into a separation column 123 together with the mobile phase and separated into individual components. A part of the sample separated into individual components is introduced into a detector 124 together with the mobile phase. As a result, the separated components of the sample are detected by the detector 124. A mobile phase containing the components of the sample is discharged from the downstream end of the detector 124.

[0027] Further, the make-up solution is supplied by the liquid supplying unit 161 of the recovery unit 160 through the ports 47, 44 of the flow path switching unit 40. Another part of the sample separated into components by the separation column 123 is introduced into the detector 130 together with the make-up solution supplied by the liquid supplying unit 161. As a result, the separated components of the sample are detected by the detector 130.

[0028] The mobile phase containing the sample components led out from the downstream end of the detector 124 is introduced into the collection section 140 through the ports 14 and 13 of the flow path switching section 10, the ports 23 and 22 of the flow path switching section 20, and the ports 34 and 35 of the flow path switching section 30. In addition, the diluent generated by the diluent generation section 151 of the dilution section 150 is introduced into each trap column 145 of the collection section 140 by the liquid delivery section 152.

[0029] In the collection section 140, the flow path between the flow path switching sections 143 and 144 is selectively switched to either a plurality of collection flow paths 141 or a bypass flow path 142 based on the detection result by the detector 124 or the detector 130. Specifically, during a period in which a mobile phase not containing a sample component is introduced into the collection section 140, the flow path between the flow path switching sections 143 and 144 is switched to the bypass flow path 142. In this case, the mobile phase introduced into the collection section 140 is discharged to the waste liquid section through the ports 25 and 24 of the flow path switching section 20.

[0030] On the other hand, during a period in which a mobile phase containing a component of the sample is introduced into the collection section 140, the flow path between the flow path switching sections 143 and 144 is switched to one of the multiple collection flow paths 141. As described above, a diluent is introduced into each trap column 145. Therefore, the sample components contained in the introduced mobile phase are collected in the trap column 145 of the collection flow path 141. The mobile phase that has passed through the collection flow path 141 is discharged to the waste liquid section through the ports 25 and 24 of the flow path switching section 20. Every time the mobile phase containing a component of the sample is introduced into the collection section 140, the above flow path switching is performed.

[0031] Figure 3 is a diagram for explaining the second dimension operation of the fraction collection system 100 of Figure 1. As shown in Figure 3, during the second dimension operation, each of the flow path switching units 10, 20, and 30 is in a first connection state. In the flow path switching unit 40, the port 45 and the port 47 are connected. This forms the flow path shown by the thick solid line in Figure 3.

[0032] In the second dimensional operation, the eluent is introduced into the collection section 140 by the liquid delivery section 161 of the collection section 160 through the ports 47 and 45 of the flow path switching section 40 and the ports 26 and 25 of the flow path switching section 20. In the collection section 140, the flow path between the flow path switching sections 143 and 144 is switched to one of a plurality of collection flow paths 141. The components of the sample collected in the trap column 145 of the collection flow path 141 are eluted by the eluent.

[0033] In the recovery section 160, the components of the sample eluted from the collection flow path 141 are introduced into the detector 162 together with the eluent through the ports 35 and 34 of the flow path switching section 30 and the ports 22 and 21 of the flow path switching section 20. As a result, the eluted components of the sample are detected by the detector 162. Based on the detection result by the detector 162, the components of the sample are recovered by the fraction collector 163 into one of a plurality of test tubes held on a tray (not shown). Every time a component of the sample is detected by the detector 162, the above-mentioned components of the sample are recovered using a different test tube.

[0034] In this embodiment, the dilution liquid is not supplied to the collection section 140 during the second dimensional operation, but the embodiment is not limited to this. When adjusting the components of the eluent introduced into the fraction collector 163, the dilution liquid may be supplied from the dilution section 150 to the collection section 140 as necessary.

[0035] (3) Effects In the fraction collection system 100 according to this embodiment, a makeup solution is supplied to the detector 130, whereby a sample that has passed through the separation column 123 is detected. In addition, an eluent is supplied to the trap column 145, whereby the sample captured in the trap column 145 is eluted. Since the makeup solution and the eluent are supplied by a common solution delivery section 161, there is no need to provide a separate device for supplying the makeup solution and a device for supplying the eluent. This makes it possible to prevent the fraction collection system 100 from becoming large and expensive.

[0036] Furthermore, the flow path switching unit 20 switches between a state in which the flow path between the trap column 145 and the separation column 123 is connected and a state in which the flow path between the trap column 145 and the liquid delivery unit 161 is connected. This makes it possible to selectively collect the sample that has passed through the separation column 123 by the trap column 145 and elute the sample collected in the trap column 145 with a simple configuration.

[0037] In addition, the flow path switching unit 40 switches between a state in which the flow path between the liquid sending unit 161 and the detector 130 is connected and a state in which the flow path between the liquid sending unit 161 and the trap column 145 is connected. This makes it possible to selectively supply the makeup solution to the detector 130 and supply the eluent to the trap column 145 with a simple configuration.

[0038] (4) Reference example The differences between the separation system according to the reference example and separation system 100 according to the present embodiment will be described below. Fig. 4 is a diagram showing the configuration of the separation system according to the reference example. As shown in Fig. 4, separation system 100A includes a liquid delivery unit 131 instead of flow path switching unit 40. In this case, port 26 of flow path switching unit 20 is connected to liquid delivery unit 161 of recovery unit 160.

[0039] The liquid sending unit 131 is, for example, a liquid sending pump, and supplies a makeup solution during the first dimension operation. In this case, a part of the sample separated into components by the separation column 123 of the separation unit 120 is introduced into the detector 130 together with the makeup solution supplied by the liquid sending unit 131. As a result, the separated components of the sample are detected by the detector 130.

[0040] The liquid delivery unit 161 pumps the eluent during the second dimension operation. In this case, the eluent supplied by the liquid delivery unit 161 is introduced into the collection unit 140 through the ports 26 and 25 of the flow path switching unit 20. As a result, the components of the sample collected in the trap column 145 of one of the collection flow paths 141 of the collection unit 140 are eluted by the eluent.

[0041] In this way, Reference example The fraction collection system 100A according to the present embodiment can also perform first and second dimensional operations, similar to the fraction collection system 100 according to the present embodiment. Reference example In this configuration, liquid sending section 131 is provided separately from liquid sending section 161. Therefore, compared to fraction collection system 100, fraction collection system 100A becomes larger and more expensive.

[0042] <2> Second embodiment (1) Configuration of the fractionation system Regarding the fraction collection system 100 according to the second embodiment, differences from the fraction collection system 100 according to the first embodiment will be described. FIG. 5 is a diagram showing the configuration of the fraction collection system 100 according to the second embodiment. As shown in FIG. 5, the fraction collection system 100 further includes an analysis section 170. The analysis section 170 includes a separation column 171, a detector 172, and a sample supply section 173. The configurations of the separation column 171 and the detector 172 are similar to those of the separation column 123 and the detector 124 of the separation section 120, respectively. As shown by the dotted line in FIG. 5, in this example, the sample supply section 173 is provided in the same liquid handler as the sample supply section 122.

[0043] In addition, the port 46 of the flow path switching unit 40 is Sample supply unit 173 of analysis unit 170The liquid delivery section 161 of the recovery section 160 is connected to the sample supply section 46 through the ports 47 and 46 of the flow path switching section 40. 173 The mobile phase is supplied to the sample supply section. 173 is provided with a tray for holding a plurality of vials and a plurality of test tubes.

[0044] FIG. 6 is a plan view showing an example of a tray provided in a liquid handler. As shown in FIG. 6, a tray 1 holds a plurality of (three in this example) container sets 2. Each container set 2 includes one vial 3 and a plurality of test tubes 4. The vial 3 contains a sample to be analyzed. Components of the sample after separation are collected and contained in each test tube 4. Therefore, before the sample is separated, each test tube 4 is empty. The components of the sample contained in each test tube 4 are analyzed in an analysis unit 170 to evaluate the purity.

[0045] (2) Operation of the fractionation system The sample supply unit 122 of the separation unit 120 collects a sample from a vial 3 of an arbitrary container set 2 placed on the tray 1, and supplies the sample to the flow path of the separation unit 120. In this state, a first dimension operation similar to that of the first embodiment is performed. The first dimension operation of the fraction collection system 100 in this embodiment is similar to that of the fraction collection system 100 in FIG. 2 in the first embodiment. As a result, the components of the sample are separated, and the separated components of the sample are collected in one of the trap columns 145 of the collection unit 140.

[0046] Fig. 7 is a diagram for explaining the second dimensional operation of the fraction collection system 100 of Fig. 5. The second dimensional operation in Fig. 7 is similar to the second dimensional operation of the fraction collection system 100 of Fig. 3 in the first embodiment, and the flow path shown by the thick solid line in Fig. 7 is formed. As a result, the components of the sample captured in the trap column 145 are eluted.

[0047] The fraction collector 163 of the collection unit 160 collects components of the sample into the test tubes 4 based on the detection result by the detector 162. In this example, the multiple components of the sample contained in the vials 3 of each container set 2 are collected into multiple test tubes 4 in the same container set 2. Therefore, the multiple test tubes 4 in each container set 2 contain components of samples that are different from each other.

[0048] Fig. 8 is a diagram for explaining the operation of the fraction collection system 100 of Fig. 5 during analysis. As shown in Fig. 8, after the components of the sample are contained in the test tube 4, the ports 46 and 47 are connected in the flow path switching unit 40. This forms the flow path shown by the thick solid line in Fig. 8. In this state, the mobile phase is supplied by the liquid delivery unit 161 in the recovery unit 160. The mobile phase is introduced into the analysis unit 170 through the ports 47 and 46 of the flow path switching unit 40.

[0049] Also, a sample is collected from any test tube 4 held on the tray 1 by a sample supply unit 173 and supplied to a flow path of the analysis unit 170. The sample supplied to the flow path of the analysis unit 170 is introduced into a separation column 171 together with a mobile phase and separated into individual components. The sample separated into individual components is introduced into a detector 172 together with the mobile phase. As a result, the separated components of the sample are detected by the detector 172. In the control unit 110, the purity of the components of the sample contained in the test tube 4 is evaluated based on the detection result by the detector 172.

[0050] (3) Effects In fraction collection system 100 according to this embodiment, a mobile phase is further supplied by liquid delivery unit 161. In the flow path of analysis unit 170, a sample collected in test tube 4 by fraction collector 163 is supplied by sample supply unit 173 to the mobile phase supplied by liquid delivery unit 161. The sample supplied by sample supply unit 173 passes through separation column 171. The sample that has passed through separation column 171 is detected by detector 172.

[0051] In this case, the purity of the sample collected in the test tube 4 can be evaluated using the detection result by the detector 172. Since the mobile phase is supplied by the liquid delivery unit 161 that supplies the make-up solution and the eluent, there is no need to provide a separate device for supplying the mobile phase. This makes it possible to prevent the fraction collection system 100 from becoming large and expensive. Here, the connection state of the flow paths is switched by the flow path switching unit 40. Therefore, the supply of the make-up solution, the supply of the eluent, and the supply of the mobile phase can be selectively performed with a simple configuration.

[0052] Furthermore, since the fraction collection system 100 is provided with the separation column 171 and the detector 172, after the sample is collected in the test tube 4, analysis for evaluating the purity of the sample can be performed continuously and automatically within the same system. Therefore, the user does not need to transport the sample collected in the test tube 4 to a separate analysis system. This improves the usability of the fraction collection system 100.

[0053] (4) First Modification In this embodiment, the sample supply unit 122 of the separation unit 120 and the sample supply unit 173 of the analysis unit 170 are provided in the same liquid handler, but the embodiment is not limited to this. Fig. 9 is a diagram showing the configuration of a fraction collection system 100 in a first modified example. As shown in Fig. 9, the sample supply unit 122 and the sample supply unit 173 of the analysis unit 170 may be provided in separate devices. In this configuration, the vial containing the sample to be analyzed and the test tube containing the separated sample do not need to be held on the same tray.

[0054] <3> Third embodiment (1) Configuration of the fractionation system The differences between the fraction collection system 100 according to the third embodiment and the fraction collection system 100 according to the second embodiment will be described below. FIG. 10 is a diagram showing the configuration of the fraction collection system 100 according to the third embodiment. As shown in FIG. 10, the fraction collection system 100 further includes a flow path switching unit 50. The flow path switching unit 50 has six ports 51-56. The configuration of the flow path switching unit 50 is similar to the configuration of the flow path switching unit 10. Therefore, the flow path switching unit 50 is switchable between a first connection state and a second connection state.

[0055] In the flow path switching unit 50, a port 51 is connected to port 44 of flow path switching section 40, and is connected to a flow path between separation column 123 and detector 124 in separation section 120. Port 52 is connected to the upstream end of detector 130. Port 53 is connected to the downstream end of detector 172 in analysis section 170. Ports 54 and 56 are connected to a waste liquid section.

[0056] (2) Operation of the fractionation system Fig. 11 is a diagram for explaining the first dimension operation of the fraction collection system 100 of Fig. 10. As shown in Fig. 11, the first dimension operation in this embodiment is the same as that in the first embodiment, except that the flow path switching unit 50 is in the first connection state. 2 Fractionation system 100 1 This is the same as the operation in the third dimension. Therefore, the flow path shown by the thick solid line in Fig. 11 is formed. In this case, the components of the sample are separated by the separation unit 120, and the components of the sample after separation are trapped in one of the trap columns 145 of the trapping unit 140.

[0057] Here, in the recovery section 160, the make-up solution is supplied by the liquid delivery section 161. The make-up solution is introduced into the ports 47 and 44 of the flow path switching section 40 and the port 51 of the flow path switching section 50. In addition, a part of the sample separated into components by the separation column 123 of the separation section 120 is introduced into the port 51 of the flow path switching section 50. Therefore, a part of the sample separated into components is introduced into the detector 130 through the ports 51 and 52 of the flow path switching section 50 together with the make-up solution. As a result, the components of the separated sample are detected by the detector 130.

[0058] After the first dimension operation, a second dimension operation is performed. The second dimension operation of the fraction collection system 100 in this embodiment is similar to the second dimension operation of the fraction collection system 100 in the second embodiment shown in Fig. 7. As a result, the components of the separated sample are collected and stored in any one of the test tubes 4 on the tray 1.

[0059] Fig. 12 is a diagram for explaining the operation of the fraction collection system 100 of Fig. 10 during analysis. As shown in Fig. 12, during analysis, the flow path switching unit 50 is in the second connection state. In the flow path switching unit 40, the port 46 and the port 47 are connected. This forms the flow path shown by the thick solid line in Fig. 12. In this case, similar to the operation during analysis of the fraction collection system 100 of Fig. 8 in the second embodiment, the separated sample supplied by the sample supply unit 173 is introduced into the analysis unit 170 together with the mobile phase supplied by the liquid delivery unit 161.

[0060] The mobile phase containing the sample delivered from the downstream end of the detector 172 of the analysis section 170 is introduced into the detector 130 through the ports 53 and 52 of the flow path switching section 50. As a result, the components of the introduced sample are detected by the detector 130. In the control section 110, the purity of the components of the sample contained in the test tube 4 is evaluated in more detail based on the detection result by the detector 130.

[0061] (3) Effects In fraction collection system 100 according to this embodiment, the sample that has passed through separation column 171 and detector 172 is detected by common detector 130. In this case, the sample that has passed through separation column 171 can be analyzed in more detail based on the detection result by detector 130.

[0062] In this configuration, there is no need to provide separate detectors for detecting samples that have passed through separation column 123 and for detecting samples that have passed through separation column 171. This makes it possible to prevent the fraction collection system 100 from becoming large and expensive. In addition, there is no need to provide multiple relatively complicated detectors 130 such as mass spectrometers, which prevents the control software for fraction collection system 100 from becoming complicated.

[0063] Furthermore, the flow path switching unit 50 switches between a state in which the flow path between the separation column 123 and the detector 130 is connected and a state in which the flow path between the separation column 171 and the detector 130 is connected. This makes it possible to selectively detect a sample that has passed through the separation column 123 and a sample that has passed through the separation column 171 with a simple configuration.

[0064] (4) Second Modification In this embodiment, detector 130 detects a sample eluted from separation column 123 of separation section 120 and also detects a sample eluted from separation column 171 of analysis section 170, but the embodiment is not limited to this. FIG. 13 is a diagram showing the configuration of fraction collection system 100 in a second modified example. As shown in FIG. 13, fraction collection system 100 does not include a flow path switching section 50. In addition, analysis section 170 further includes detector 174. Detector 174 has a similar configuration to detector 130 and is provided downstream of detector 172.

[0065] In this example, detector 130 detects a part of the sample eluted from separation column 123 during the first dimension operation. Meanwhile, detector 174 of analysis section 170 detects the sample eluted from separation column 171 and led out from the downstream end of detector 172 during analysis after the second dimension operation. Note that detector 174 may be provided downstream of detector 172 in fraction collection system 100 according to the first modified example of FIG.

[0066] <4> Other embodiments (1) In the above embodiment, the separation unit 120 is provided with the detector 124, and the collection unit 160 is provided with the detector 162, but the embodiment is not limited to this. As long as any sample component can be collected in the trap column 145 of the collection unit 140, the separation unit 120 does not necessarily need to be provided with the detector 124, and the collection unit 160 does not necessarily need to be provided with the detector 162.

[0067] In the third embodiment, the detector 172 is provided in the analysis unit 170, but the embodiment is not limited to this. As long as the components of the sample can be detected by the detector 130 or the detector 174, the detector 172 does not have to be provided in the analysis unit 170.

[0068] (2) In the above embodiment, the detector 130 is a mass spectrometer, but the embodiment is not limited thereto. The detector 130 may be another detector capable of detecting components of the sample introduced together with the make-up solution. For example, the detector 130 may be a flame ionization detector, a light scattering detector, a charged particle detector, or the like.

[0069] Similarly, in the second modification, the detector 174 of the analysis unit 170 is a mass spectrometer, but the embodiment is not limited to this. The detector 172 may be another detector capable of detecting components of the sample introduced together with the make-up solution, or may be a detector of a different type from the detector 130.

[0070] <5> Correspondence between each component of the claims and each part of the embodiment Below, examples of the correspondence between each component of the claims and each part of the embodiment will be described, but the present invention is not limited to the following examples. Various other elements having the configuration or function described in the claims can also be used as each component of the claims.

[0071] In the above embodiment, the sample supply units 122 and 173 are examples of the first and second sample supply units, respectively, and the separation columns 123 and 171 are examples of the first and second separation columns, respectively. The detector 130 is an example of a first detector or a common detector, the detectors 172 and 174 are examples of a second detector, the liquid delivery unit 161 is an example of a liquid delivery unit, and the flow path switching units 40 and 50 are examples of the first and second flow path switching units, respectively.

[0072] <6> Aspects It will be appreciated by those skilled in the art that the above exemplary embodiments are illustrative of the following aspects.

[0073] (Item 1) A separation system according to one embodiment comprises: A mobile phase supply unit that supplies a first mobile phase; a first sample supply unit that supplies a sample to the first mobile phase supplied by the mobile phase supply unit; a first separation column through which the sample supplied by the first sample supply unit passes; a first detector for detecting the sample that has passed through the first separation column; a trap column that collects components of the sample that have passed through the first separation column based on a detection result by the first detector; The apparatus may further include a liquid delivery unit that delivers a make-up solution to the first detector and delivers an eluent for eluting a sample to the trap column.

[0074] In this preparative system, the make-up solution is supplied to the first detector, whereby the sample that has passed through the first separation column is detected. Also, the eluent is supplied to the trap column, whereby the sample captured in the trap column is eluted. Since the make-up solution and the eluent are supplied by a common liquid delivery section, there is no need to provide separate devices for supplying the make-up solution and the eluent. This makes it possible to prevent the preparative system from becoming large and expensive.

[0075] (2) The separation system according to (1), The liquid supply system may further include a first flow path switching unit that is switchable between a state in which a flow path between the liquid supply unit and the first detector is connected and a state in which a flow path between the liquid supply unit and the trap column is connected.

[0076] In this case, the supply of the make-up solution to the first detector and the supply of the eluent to the trap column can be selectively performed with a simple configuration.

[0077] (Item 3) The separation system according to item 1 or 2, The apparatus may further include a fraction collector that collects the sample eluted from the trap column in a container.

[0078] In this case, the sample trapped in the trap column can be recovered and stored in a container.

[0079] (Item 4) The separation system according to item 3, a second sample supply unit that supplies the sample collected in the container by the fraction collector to a second mobile phase; a second separation column through which the sample supplied by the second sample supply unit passes; and a second detector for detecting the sample that has passed through the second separation column; The liquid delivery section may further supply the second mobile phase.

[0080] In this case, the purity of the sample collected in the container can be evaluated using the detection result by the second detector. Here, since the second mobile phase is supplied by the same liquid supplying part that supplies the make-up solution and the eluent, there is no need to provide a separate device for supplying the second mobile phase. This makes it possible to prevent the separation system from becoming large and expensive.

[0081] (Item 5) The separation system according to item 2, a fraction collector that collects the sample eluted from the trap column in a container; a second sample supply unit that supplies the sample collected in the container by the fraction collector to a second mobile phase; a second separation column through which the sample supplied by the second sample supply unit passes; and a second detector for detecting the sample that has passed through the second separation column; The liquid delivery section further supplies the second mobile phase, The first flow path switching unit may be further switchable to a state in which the flow path between the liquid delivery unit and the second sample supply unit is connected.

[0082] In this case, the purity of the sample collected in the container can be evaluated using the detection result by the second detector. Here, since the second mobile phase is supplied by the same liquid supplying part that supplies the make-up solution and the eluent, there is no need to provide a separate device for supplying the second mobile phase. This makes it possible to prevent the separation system from becoming large and expensive.

[0083] In addition, the connection state of the flow paths is switched by the first flow path switching unit, so that the supply of the make-up solution, the supply of the eluent, and the supply of the second mobile phase can be selectively performed with a simple configuration.

[0084] (Item 6) In the separation system according to item 4 or 5, The first detector and the second detector may be configured as a common detector that selectively detects a sample that has passed through the first separation column and a sample that has passed through the second separation column.

[0085] In this case, there is no need to provide a first detector and a second detector separately, which makes it possible to prevent the fraction collection system from becoming large and expensive.

[0086] (Item 7) The separation system according to item 6, The system may further include a second flow path switching unit that is switchable between a state in which a flow path between the first separation column and the common detector is connected and a state in which a flow path between the second separation column and the common detector is connected.

[0087] In this case, detection of the sample that has passed through the first separation column and detection of the sample that has passed through the second separation column can be selectively performed with a simple configuration.

[0088] (Item 8) In the fraction collection system according to any one of items 1 to 7, The first detector may include a mass spectrometer.

[0089] In this case, the components of the sample that has passed through the first separation column can be analyzed in detail.

Claims

1. A mobile phase supply unit that supplies a first mobile phase; a first sample supply unit that supplies a sample to the first mobile phase supplied by the mobile phase supply unit; a first separation column through which the sample supplied by the first sample supply unit passes; a first detector for detecting a sample that has passed through the first separation column; a trap column that collects components of the sample that have passed through the first separation column based on a detection result by the first detector; a liquid delivery unit that delivers a make-up solution to the first detector and delivers an eluent for eluting a sample to the trap column.

2. The separation system of claim 1 , further comprising a first flow path switching unit that can be switched between a state in which the flow path between the liquid delivery unit and the first detector is connected and a state in which the flow path between the liquid delivery unit and the trap column is connected.

3. The fraction collection system according to claim 1 , further comprising a fraction collector configured to collect the sample eluted from the trap column in a container.

4. a second sample supply unit that supplies the sample collected in the container by the fraction collector to a second mobile phase; a second separation column through which the sample supplied by the second sample supply unit passes; and a second detector for detecting the sample that has passed through the second separation column; The fraction collection system according to claim 3 , wherein the liquid delivery section further supplies the second mobile phase.

5. a fraction collector that collects the sample eluted from the trap column in a container; a second sample supply unit that supplies the sample collected in the container by the fraction collector to a second mobile phase; a second separation column through which the sample supplied by the second sample supply unit passes; and a second detector for detecting the sample that has passed through the second separation column; The liquid delivery unit further supplies the second mobile phase, The fractionation system according to claim 2 , wherein the first flow path switching unit is further switchable to a state in which the flow path between the liquid delivery unit and the second sample supply unit is connected.

6. The separation system of claim 4, wherein the first detector and the second detector are configured as a common detector that selectively detects samples that have passed through the first separation column and samples that have passed through the second separation column.

7. The separation system according to claim 6, further comprising a second flow path switching unit switchable between a state in which a flow path between the first separation column and the common detector is connected and a state in which a flow path between the second separation column and the common detector is connected.

8. The fraction collection system of claim 1 , wherein the first detector comprises a mass spectrometer.

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