JP6682923B2 - Fluid chromatograph - Google Patents

Description

  The present invention relates to a fluid chromatograph, for example, a liquid chromatograph or a supercritical fluid chromatograph, in which a sample is injected into an analysis channel in which a mobile phase flows, and the sample is separated and detected for each component in a separation column, The present invention relates to a fluid chromatograph having a function of simultaneously introducing a sample into a plurality of columns.

  For example, in order to study the conditions for analyzing a chiral compound by liquid chromatography, it is necessary to find a combination of a separation column and a mobile phase suitable for separating a target analyte by trial and error. Conventionally, it is possible to selectively switch the separation column to be used by connecting a plurality of separation columns via a switching valve to the subsequent stage of the sample injection unit for injecting the sample into the analysis channel. The apparatus was configured and the separation analysis using each separation column was sequentially executed.

  In the above method, while performing analysis using one separation column, other separation columns are not used and only stand by, which is inefficient and requires a long time for studying analysis conditions. There was a problem. Therefore, if a plurality of separation columns are connected in parallel and the plurality of separation columns are simultaneously analyzed, it is possible to shorten the time required to study the analysis conditions.

  However, since the flow path resistance of the separation column provided in each column flow path varies depending on the type and individual difference of the separation column, the flow rate of the mobile phase varies in each column flow path, and the sample is evenly introduced into each separation column. However, there are problems that the detection sensitivity varies depending on the flow channel, and that the flow channel with a small flow rate of the mobile phase requires a long retention time in the separation column and a long analysis time.

  Therefore, an object of the present invention is to make it possible to search for a combination of a separation column and a mobile phase suitable for separating a target component with high efficiency and accuracy.

  The fluid chromatograph according to the present invention, a mobile phase liquid sending unit for sending a mobile phase, and a sample in a flow path in which the mobile phase from the mobile phase liquid sending unit flows downstream of the mobile phase liquid sending unit. A sample injection part for injecting, each having a separation column for separating the sample injected by the sample injection part for each component, and a plurality of column channels connected in parallel to each other on the downstream side of the sample injection part, A pressure control valve provided on each of the column flow passages, for adjusting the flow passage resistance of the column flow passage, and provided on the upstream side of the pressure control valve on each of the column flow passages, in the column flow passage And a detector provided downstream of the separation column for detecting the sample component separated by the separation column.

  It is preferable that a flow path resistance that prevents interference of the pressure sensor with pressure in another column flow path is provided on the upstream side of the pressure sensor on each column flow path. By doing so, it is possible to prevent the pressure sensor in each column flow channel from being interfered with by another column flow channel and being unable to accurately detect the pressure in the column flow channel.

  It is preferable that the pressure regulating valve automatically regulates the flow passage resistance of the column flow passage so that the pressure value detected by the pressure sensor becomes a set value. Then, it is easy to adjust the flow path resistance of each column flow path.

  In the fluid chromatograph of the present invention, on a plurality of column channels each having a separation column and connected in parallel with each other, a pressure control valve for controlling the channel resistance of the column channel and the column channel Since the pressure sensor for detecting the pressure is provided, the flow path resistance of each column flow path can be adjusted by the pressure control valve based on the pressure value detected by the pressure sensor. Thereby, it becomes easy to make the flow path resistances of the respective column flow paths substantially the same, and the flow rates of the mobile phases flowing in the respective column flow paths connected in parallel can be made substantially the same. Therefore, the analysis using a plurality of separation columns can be performed accurately, and the search for the combination of the separation column and the mobile phase suitable for the separation of the target component can be performed with high efficiency and accuracy.

  As described above, when the pressure control valve is not provided in each column channel, in order to make the flow rate of the mobile phase flowing in each column channel approximately the same, on each column channel, in the separation column of the column channel It is possible to adjust the flow path resistance of each column flow path to be substantially the same by providing a corresponding flow path resistance. However, even if the separation column is a separation column of the same type, there are individual differences in the flow path resistance.Therefore, whenever the separation column is replaced, prepare a flow path resistance according to the new separation column. The piping needs to be reassembled.

  On the other hand, in the present invention, even when the separation column is exchanged, the flow path resistance of the column flow path can be adjusted by the pressure control valve, so that it is not necessary to reassemble the pipe according to the separation column.

It is a flow-path diagram which shows schematically the liquid chromatograph which is one Example of a fluid chromatograph. It is a flow-path figure which shows the state which switched the flow-path structure in the Example in general. FIG. 6 is a flow chart schematically showing a configuration for verifying a difference in flow rate of each column flow passage depending on the presence or absence of a pressure control valve. It is a flow-path block diagram which shows the experiment apparatus for verifying the influence on the mobile phase flow rate by the presence or absence of a pressure control valve.

  Hereinafter, a liquid chromatograph, which is an example of a fluid chromatograph, will be described with reference to the drawings. An example in which the present invention is applied to a liquid chromatograph will be described below, but the present invention can also be applied to a supercritical fluid chromatograph.

  As shown in FIG. 1, the liquid chromatograph of this example includes a mobile phase liquid feeding section 2 for feeding a mobile phase and a port to which a flow path 6 from the mobile phase liquid feeding section 2 is connected. The switching valve 8 provided in the center, the column flow channel groups 20a and 20b, one ends of which are respectively connected to different ports of the plurality of ports provided in the switching valve 8, and the other ends of the column flow channel groups 20a and 20b are respectively connected. The switching valve 24 having the opened port and the detector 28 connected to the central port of the switching valve 24 via the flow path 26 are provided.

  The mobile phase liquid feed unit 2 has liquid feed pumps 2a and 2b for feeding different kinds of solvents, the solvents fed by the pumps 2a and 2b are mixed by a mixer 4, and the mixed liquid is moved. Liquid is sent through the flow path 6 as a phase.

  The switching valve 8 has a central port (hereinafter, referred to as a central port) to which the flow path 6 is connected and six ports (hereinafter, referred to as selection ports) evenly arranged around the central port. . One end of the column flow channel group 20a is connected to one of the selection ports of the switching valve 8, and the column flow channel is connected to one of the selection ports adjacent to the selection port to which the column flow channel group 20a is connected. One end of the group 20b is connected.

  In the switching valve 8, the flow path 22 for feeding the mobile phase for performing the equilibration process of the separation column is connected to the other select port adjacent to the select port to which one end of the column flow path group 20a is connected. ing. The flow channel 22 is also connected to a selection port adjacent to the selection port to which one end of the column flow channel group 20b is connected. The two selection ports adjacent to the two selection ports to which the flow path 22 is connected are closed ports.

  The switching valve 8 includes one flow path that connects the central port and any one of the selection ports, and two flow paths that connect two selection ports that are adjacent to each other. Thereby, the switching valve 8 connects the flow path 6 and the column flow path group 20a and simultaneously connects the flow path 22 and the column flow path group 20b (state of FIG. 1), or 6 and the column flow channel group 20b are connected, and at the same time, the flow channel 22 and the column flow channel group 20a are connected to each other (state of FIG. 2).

  The switching valve 24 has a central port to which the flow path 26 is connected and six selection ports evenly arranged around the central port. The other end of the column flow channel group 20a is connected to one of the selection ports, and one of the selection ports adjacent to the selection port to which the column flow channel group 20a is connected is connected to the column flow channel group 20b. The other end is connected.

  The two selection ports adjacent to the selection ports to which the column flow path groups 20a and 20b are connected respectively communicate with the drain, and the remaining two selection ports adjacent to those selection ports have no flow paths. Not connected.

  The switching valve 24 includes one flow path that connects the central port and any one of the selection ports, and two flow paths that connect between two selection ports that are adjacent to each other. As a result, the switching valve 24 connects the channel 26 and the column channel group 20a and simultaneously connects the column channel group 20b to the drain (state of FIG. 1), or the channel 26 and the column channel. At the same time when the column flow channel group 20a is connected to the group 20b, the column flow channel group 20a is switched to either of the states (the state of FIG. 2).

  Each of the column flow channel groups 20a and 20b is configured by connecting four column flow channels 10 in parallel. That is, this liquid chromatograph has a total of eight column channels 10. A resistance tube 12, a pressure sensor 14, a pressure control valve 16, and a separation column 18 are provided on each column flow path 10 from the switching valve 8 side (left side in FIGS. 1 and 2).

  In the liquid chromatograph of this example, the mobile phase liquid sending unit 2-column channel group 20a-detector 28 is connected and channel 22-column channel group 22b-drain is simultaneously connected (state of FIG. 1). , Or the state in which the mobile phase liquid sending unit 2-column channel group 20b-detector 28 is connected and channel 22-column channel group 22a-drain is connected at the same time (state of FIG. 2). Can be switched. In the state of FIG. 1, the sample is analyzed using the column channel group 20a, and at the same time, the respective separation columns 18 of the column channel group 20b are equilibrated. In the state of FIG. 2, the sample is analyzed using the column channel group 20b, and at the same time, the respective separation columns 18 of the column channel group 20a are equilibrated.

  Each pressure sensor 14 detects the pressure in each column flow path 10. Each pressure control valve 16 controls the flow path resistance of each column flow path 10. In this embodiment, the pressure control valve 16 is a back pressure control valve as disclosed, for example, in WO / 2015/029251. The operation of each pressure control valve 16 is controlled by the controller 30 as shown in FIG.

  In FIG. 3, the pressure sensor 14 and the pressure control valve 16 provided in each column flow path 10 are shown as pressure sensors 14-1, 14-2, ... 14-8, and pressure control valves 16-1, 16-, respectively. 2, ... 16-8. The control unit 30 is preset with a pressure value in each column flow channel 10 required to make the flow channel resistances of the respective column flow channels 10 substantially the same, and the control unit 30 controls each pressure sensor 14-1. , 14-2, ... 14-8 so that the pressure values detected by the pressure control valves 16-1, 16-2, ... 16-8 are feedback-controlled.

  The control unit 30 may be a dedicated computer provided in this liquid chromatograph or a general-purpose personal computer.

  In this embodiment, the pressure control valves 16-1, 16-2, ... 16-8 are controlled by the common control unit 30, but the pressure control valves 16-1, 16-2, ... 16-2, ... 16-8 has its own control unit, and the detection values of the pressure sensors 14-1, 14-2, ... 14-8 are pressure control valves 16-1, 16-2. The feedback control may be individually performed so that each set value is set to 16-8.

  Further, the pressure control valve 16 may be of a manual valve type in which the user manually changes the flow passage width by tightening the stopper.

  Returning to FIG. 1, the resistance tube 12 provided on the upstream side of the pressure sensor 14 in each column flow channel 10 is provided in the other column flow channel 10 in the column flow channel group 20a or 20b in which the pressure sensor 14 is the same. This is to prevent pressure interference. Since the column flow channels 10 of each column flow channel group 20a, 20b are connected in parallel, if there is no resistance tube 12, the pressure sensor 14 in each column flow channel 10 in the same column flow channel group 20a or 20b However, the upstream side portion is likely to have the same pressure, and the pressure sensor 14 may not be able to accurately detect the pressure in each column channel 10 due to the interference of the pressure in the other column channels 10.

  For example, when the set value of a certain pressure sensor 14 is 30 MPa, the pressure in another column flow passage 10 is not changed even though the pressure in that column flow passage 10 actually reaches 30 MPa. Since it is lower than the above, the pressure in the other column flow channel 10 is interfered with to detect a pressure lower than 30 MPa, and the pressure control valve 16 operates to further increase the flow channel resistance based on the detected value. As a result, a phenomenon occurs in which the mobile phase hardly flows in the column flow path 10.

  By providing the resistance tube 12 on the upstream side of the pressure sensor 14 of each column flow path 10, there is a time lag until the pressure on the downstream side of the resistance tube 12 is affected by the pressure on the upstream side of the resistance tube 12. Due to the time difference, each pressure sensor 14 can detect the actual pressure in the column flow path 10, and the pressure control valve 16 can be operated correctly.

  In the above embodiment, each column channel 10 is configured to be connected to the common detector 28 via the switching valve 24, but each column channel 10 may be provided with a detector.

  The verification result of the effect of providing the pressure control valve in the flow paths connected in parallel with each other will be described. This verification was performed using the experimental apparatus having the flow channel configuration shown in FIG. In the experimental apparatus of FIG. 4, two flow paths 34a and 34b are connected in parallel on the downstream side of the pump 32 that feeds the mobile phase, and resistance tubes 36a and 36b are connected on the respective flow paths 34a and 34b from the upstream side. , Pressure sensors 38a and 38b, pressure control valves 40a and 40b, separation columns 42a and 42b, and detectors 44a and 44b.

  In this verification, the same kind of columns are used as the separation columns 42a and 42b, water is sent at a flow rate of 1 mL / min as the mobile phase, and the time from the start of the solution delivery until the mobile phase reaches the detectors 44a and 44b. Was measured. As a result of verification by turning off the drive of the pressure control valves 40a and 40b, the time until the detectors 44a and 44b detect the mobile phase is 0.362 minutes at the detector 44a and 0. It was 547 minutes. On the other hand, the pressure control valves 40a and 40b are turned on, and the setting values of the respective pressures are set to 11.2 MPa and 11.1 MPa. As a result of the verification, the detectors 44a and 44b detect the mobile phase. It was 0.414 minutes for the detector 44a and 0.477 minutes for the detector 44b. From this, it was found that the flow rate of the mobile phase flowing through the flow paths 44a and 44b can be made uniform by adjusting the flow path resistance of the flow paths 34a and 34b by the pressure control valves 44a and 44b.

  The same verification was performed with the resistance tubes 36a and 36b removed in the configuration of FIG. 4, but the pressure sensor 38b interferes with the pressure in the flow path 34a to accurately detect the pressure in the flow path 34b. It was confirmed that the pressure control valve 40b closed the flow path 34b and the mobile phase hardly flowed through the flow path 34b.

2 Mobile Phase Liquid Delivery Part 2a, 2b Liquid Delivery Pump 4 Mixer 6,22,26 Flow Path 8,24 Switching Valve 10 Column Flow Path 12 Resistance Tube 14 Pressure Sensor 16 Pressure Control Valve 18 Separation Column 20a, 20b Column Flow Path Group 28 detector 30 controller

Claims (3)

A mobile phase liquid sending part for sending a mobile phase,
A sample injection unit for injecting a sample into the flow path in which the mobile phase from the mobile phase liquid supply unit flows on the downstream side of the mobile phase liquid supply unit,
Each has a separation column for separating the sample injected by the sample injection unit for each component, and a plurality of column channels connected in parallel to each other on the downstream side of the sample injection unit,
A pressure control valve provided on each of the column channels, for controlling the channel resistance of the column channel,
A pressure sensor that is provided on the upstream side of the pressure control valve on each of the column channels and detects the pressure in the column channel,
The pressure value in each column channel required to make the channel resistance of each column channel the same is preset, and the pressure value detected by each pressure sensor is the preset pressure value. So that the feedback control of the pressure control valve ,
A fluid chromatograph provided with a detector which is provided on the downstream side of the separation column and detects a sample component separated by the separation column.   The fluid chromatograph according to claim 1, wherein a resistance tube that prevents interference of the pressure sensor with another pressure in the column channel is provided on the upstream side of the pressure sensor on each column channel. Two column flow channel groups each including a plurality of column flow channels connected in parallel to each other are provided,
A flow path for feeding a mobile phase for carrying out the equilibration process of the separation column is provided separately from the mobile phase feeding section,
A switching valve is provided that connects one of the column flow channel groups between the mobile phase liquid sending section and the detector and at the same time connects the other column flow channel group between the flow channels and the drain. ,
The fluid chromatograph according to claim 1 or 2, which is configured to analyze a sample by using one of the column flow channel groups and at the same time perform equilibration of the separation column of the other column flow channel group. Graph.

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