JP3341716B2 - Liquid chromatograph - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a liquid chromatograph for separating and analyzing various compounds in a sample, such as a high performance liquid chromatograph (hereinafter referred to as HPLC).

[0002]

2. Description of the Related Art FIG. 1 is a schematic flow path diagram showing a conventional HPLC. The column 5 for separating the sample, the pump unit 1 for sending the mobile phase to the column 5, and the sample are collected from the sampling needle 39 to the sampling loop 27, and the collected sample is switched to the column 5 by switching the flow path switching valve 29. Auto-injector 3 introduced into the mobile phase flow path upstream of
A detection unit 7 for detecting a sample separated by the column 5;
The control unit 41 is configured to control operations of the pump unit 1 and the auto injector 3.

The pump section 1 is provided with a double plunger reciprocating liquid feed pump 9. The suction side of the primary pump head 11 of the pump 9 is connected to a mobile phase container 15 in which a mobile phase is stored via a check valve 13a, and the discharge side is suction of a secondary pump head 17 via a check valve 13b. Connected to the side. Secondary pump head 1
The discharge side of 7 is connected to the auto injector 3 via a drain valve 19 and a line filter 21.
A pressure sensor 23 is provided in a flow path between the secondary pump head 17 and the drain valve 19. By manually switching the lever 25, the drain valve 19
The discharge side of the secondary pump head 17 can be switched to the auto injector 3 or the drain for connection.

The auto-injector 3 is provided with a 2-position 6-port valve 29 for switching the flow path from the pump section 1 to the sampling loop 27 or the column 5 for connection. The sampling loop 27 is connected to a sampling needle 39 that moves between the injection port 35 and the sample container 37, sucks a sample from the sample container 37, and discharges the sample to the injection port 35. The injection port 35 is connected to the column 5 by switching the valve 29. Valve 29-1
A measuring syringe 33 is connected to the two ports via a three-way valve 31, and is connected to the sampling loop 27 by switching the valve 29. Downstream of the column 5, a detection unit 7 for detecting the sample separated in the column 5 is connected. A thin tube is used for the flow path between the injection port 35 and the valve 29, the flow path between the valve 29 and the column 5, and the flow path between the column 5 and the detection unit 7 to prevent dilution of the sample.

In this conventional example, when the whole flow path is filled with the mobile phase or the mobile phase is replaced when the apparatus is started, the inside of the pump 9 has a relatively large volume, so that the pump 9 operates at a low speed as usual. When the mobile phase flows, it takes a considerable time to replace the mobile phase inside the pump. However, when the mobile phase flows at a high speed, the pressure after the injection port 35 including the column 5 increases because the piping is thin. Therefore, the mobile phase cannot flow at a high speed in the flow path after the injection port 35. Therefore, the pump 9 switches the drain valve 19 to the drain side and then drives the pump 9 at high speed to introduce the mobile phase into the pump 9.

The operation will be described. First, the discharge side of the secondary pump head 17 is connected to the drain by manually moving the lever 25 of the drain valve 19. Next, the pump 9 is driven at a high speed to discharge the mobile phase from the drain via the drain valve 19. After the interiors of the primary pump head 11 and the secondary pump head 17 are filled with the new mobile phase, the pump 9 is returned to a normal speed, and the lever 25 of the drain valve 19 is manually switched to switch the secondary pump head. The discharge side of 17 is connected to the auto injector 3, and a new mobile phase flows through the entire flow path.

[0007]

Manually opening and closing the drain valve to fill or replace the mobile phase involves:
Since it is a complicated operation for the operator, automation is desired. However, when attempting to automate the opening and closing of the drain valve, a high pressure is applied to the drain valve, so that a high-torque motor is required, which increases the cost of the apparatus. Therefore, an object of the present invention is to automate filling or replacement of a mobile phase in a liquid chromatograph without increasing costs.

[0008]

According to the liquid chromatograph of the present invention, a column for separating a sample, a liquid sending section for sending a mobile phase to the column, a sample from a sampling needle to a sampling loop, and a sample are collected. Introduces the sample into the mobile phase flow path upstream of the column by switching the flow path switching valve, controls the detector that detects the sample separated by the column, and controls the operation of the liquid sending section and the sample introduction section A liquid chromatograph comprising: a drain port for discharging a liquid discharged from a sampling needle to the outside; and the control unit, in addition to the above control, switching a flow path switching valve to feed the liquid. Section is connected to the flow path leading to the sampling needle via the sampling loop, and the sampling needle is positioned at the drain port to drive the liquid sending section. Control of the operation of switching to the fast drive is also intended to do.

When a signal for filling the flow path with the mobile phase or a signal for exchanging the mobile phase is sent from the outside to the control section, the control section controls the liquid sending section and the sample introduction section to operate the flow path switching valve. By switching, the liquid sending section is connected to the sampling needle side, the sampling needle is moved from the injection port to the drain port, and the flow rate of the liquid sending section is increased.
The mobile phase is discharged out of the apparatus at a high speed from the liquid sending unit via the flow path switching valve, the sampling loop, the sampling needle, and the drain port, and the flow path is filled or replaced with a desired mobile phase. Thereafter, the sampling needle is returned to the injection port, and the flow rate of the pump is returned to a low speed to feed the liquid, thereby completing the mobile phase filling or replacement of the entire flow path.

[0010]

DESCRIPTION OF THE PREFERRED EMBODIMENTS An example of a flow path switching valve in a sample introduction section is a two-position valve, in which a liquid supply section is connected to a column via a sampling loop and a liquid supply section is directly connected to a column. At the position where the liquid sending section is directly connected to the column, the flow path is connected so that the measuring member for sampling is connected to the sampling loop.

Another example of the flow path switching valve in the sample introduction section is 3
A position valve that connects the liquid sending section to the column via the sampling loop, a position that directly connects the liquid sending section to the column, and a position that connects the liquid sending section to the sampling loop and closes the upstream of the column. At the position where the liquid sending section is directly connected to the column, the flow path is connected so that the measuring member for sampling is connected to the sampling loop.
In order to facilitate the replacement of the mobile phase, a plurality of mobile phase containers containing different mobile phases are connected to the suction side of the liquid sending section via respective solenoid valves, and these solenoid valves are opened and closed. It is preferred that the mobile phase can be selected.

[0012]

FIG. 2 is a schematic flow diagram showing an embodiment of the present invention. A pump section (liquid sending section) 2 for sending a mobile phase, an auto injector (sample introducing section) 4 for introducing a sample into a flow path, a column 6 for separating a sample, and a detecting section 8 for sequentially detecting the separated sample. It is configured.

The pump section 2 is provided with a double plunger reciprocating liquid feed pump 10 as an example. The suction side of the primary pump head 12 of the pump 10 is connected via a check valve 14a to a mobile phase container 16 in which the mobile phase is stored, and the discharge side is suctioned by a secondary pump head 18 via a check valve 14b. Connected to the side. The discharge side of the secondary pump head 18 is connected to the auto injector 4 via a line filter 20 for removing foreign matter mixed in the mobile phase. A pressure sensor 22 is provided in a flow path between the secondary pump head 18 and the line filter 20.

The auto-injector 4 is provided with a 2-position 6-port valve 26 for switching the flow path from the pump section 2 to the sampling loop 24 or the column 6 for connection. The sampling loop 24 is connected to a sampling needle 36 that moves between the injection port 32 and the sample container 34, sucks a sample from the sample container 34, and discharges the sample to the injection port 32. A drain port 38 for discharging the liquid to the outside is provided beside the injection port 32. The sampling needle 36 can also move to the drain port 38, and the waste liquid can be discharged to the outside of the apparatus via the drain port 38. The injection port 32 is connected to the valve 26
Is connected to the column 6 by switching. One port of the valve 26 has a metering syringe 30 via a three-way valve 28.
Is connected to the sampling loop 24 by switching the valve 26.

Downstream of the column 6, a detection unit 8 for detecting the sample separated in the column 6 is connected. The flow path between the injection port 32 and the valve 26, the valve 26-
A thin tube is used for the flow path between the columns 6 and the flow path between the column 6 and the detection unit 8 in order to prevent dilution of the sample. A control unit 40 is provided for controlling operations of the pump unit 2 and the auto injector 4. Control unit 40
Is a flow path switching valve 2 in addition to controlling the sample introduction and analysis operations.
6, the pump unit 2 is connected to the sampling needle 36 via the sampling loop 24, and the sampling needle 36 is connected to the drain port 38 to control the operation of switching the driving of the pump unit 2 to high-speed driving.

In this embodiment, the operation at the time of analysis will be described. The control unit 40 connects the flow path from the pump unit 2 to the column 6 by the valve 26 to flow the mobile phase through the column 6,
The metering syringe 30 is connected to the sampling loop 24. The sampling needle 36 is moved to the sample container 34, and the sample is sucked into the sampling loop 24 by the measuring syringe 30.

Thereafter, the sampling needle 36 is moved to the injection port 32, and the valve 26 is moved to the position shown in FIG.
Switch to state. As a result, the mobile phase flows into the column 6 from the connection between the sampling needle 36 and the injection port 32 through the sampling loop 24, and the sample collected in the sampling loop 24 is injected into the column 6 and separated therefrom. Is detected by

Next, the operation when the flow path is filled with the mobile phase or the mobile phase is replaced will be described. When a signal for introducing or replacing the mobile phase is sent from the outside to the control unit 40, the control unit 40 switches the valve 26 to connect the flow path from the pump unit 2 to the sampling needle 36 via the sampling loop 24, Sampling needle 3
6 to the drain port 38. Thus, a flow path of the mobile phase container 16 → the pump 10 → the switching valve 26 → the sampling loop 24 → the sampling needle 36 → the drain port 38 is formed. In the flow path state, the control unit 40 drives the pump 10 at a high speed to feed the mobile phase at a high speed. By driving the pump 10 for a predetermined time, a desired mobile phase is introduced into a flow path from the inside of the pump 10 to the sampling needle 36. The mobile phase discharged from the sampling needle 36 during the high-speed driving of the pump 10 is discharged to the outside of the device via the drain port 38.

After a lapse of a predetermined time, the sampling needle 3
6 to the injection port 32, the pump 10 is returned to the normal driving speed, and the liquid is sent at a low speed. The flow path between the injection port 32 and the valve 26, the flow path between the valve 26 and the column 6, and the column 6-detecting unit The mobile phase is introduced into the channel between the eight. Although the detailed description of the switching operation of the valve 26 is omitted, the switching is appropriately performed, including when the sampling needle 36 is moved. According to the present invention, not only is the motor of the drain valve unnecessary, but also
The drain valve itself becomes unnecessary. As a result, the introduction or replacement of the mobile phase can be automated without increasing the cost of the device.

FIG. 3 is a schematic diagram showing a part of another embodiment. Mobile phase containers 42a and 42 each containing a mobile phase are provided on the suction side of the primary side pump head of the pump unit.
b, 42c and a cleaning liquid container 42d containing the cleaning liquid are connected via electromagnetic valves 44a, 44b, 44c, 44d, respectively. Solenoid valves 44a, 44b, 44c, 44
Since the mobile phase or washing solution can be selected by controlling the opening and closing of d, it is possible to select and replace the mobile phase with just a button operation, and to automate the flow channel washing process after analysis. become.

FIG. 4 shows still another embodiment. The autosampler 4a corresponding to the autoinjector 4 in the embodiment of FIG. 2 includes a high-pressure valve 50 and a low-pressure valve 52 so as to switch the flow path. The high pressure valve 50 is
The stator is provided with six ports, and the rotor is provided with three flow grooves A, B, and C to switch the connection between the ports. The channel groove A is a channel groove for switching the port to the port or the port for connection, the channel groove B is a channel groove for switching the port to the port or the connection, and the channel groove C is the port. Is a channel groove for switching and connecting to a port or a port.

The flow channel A has a flow channel that is longer than the distance from the port or from the port. That is, a part of the channel groove A is formed by extending the channel groove beyond the rotation of 60 °. This allows not only the connection of the ports to the ports or the ports, but also the state where the flow grooves B and C do not connect the ports as shown in the auto drain position in FIG. 9 described later. The high-pressure valve 50 is a three-position valve.

The stator of the low-pressure valve 52 has four ports a to d, and its rotor has a position connecting ports b and c and a port d and a as shown in FIG. Position and FIG. 9 described later
As shown in (1), there is provided a channel groove that can take three positions, that is, a position where none of the ports is connected. Therefore, the low pressure valve 52 is also a three-position valve.

The port of the high pressure valve 50 is connected to the pump unit 2
Is connected to the flow path of the mobile phase container 16 to which the mobile phase is supplied. A sampling loop 24 is provided in the flow path connected to the port, and a sampling needle 36 is provided at the tip of the flow path. The flow path connected to the port is connected to the port b of the low-pressure valve 52 via the measuring pump 30a corresponding to the measuring syringe 30 in the embodiment of FIG. The port is connected to port a of the low-pressure valve 52. An injection port 32 is connected to the port. Port 6
The analysis flow path connected to the detection unit 8 through the detection unit 8 is connected.

FIG. 2 shows another port c of the low-pressure valve 52.
The rinsing port 38a also serving as the drain port 38 of the embodiment is connected to the rinsing port 38a. A rinsing liquid for washing the sampling needle 36 is supplied to the rinse port 38a, and the mobile phase can be discharged from the sampling needle 36. Thus, it also functions as a drain port. The rinsing liquid and the mobile phase overflow from the rinsing port 38a and are discharged to the drain. A flow path leading to another port d is led to the rinsing liquid 54.

FIGS. 4 to 8 show the sampling operation in order of position. FIG. 4A shows a (A) Ready (during analysis) position, in which the high pressure valve 50 is connected to and from the port, and the pump unit 2 is connected.
The mobile phase sent out from the column passes through the sampling loop 24, and flows from the column 6 to the flow path passing through the detection unit 8 through the connection point between the sampling needle 36 and the injection port 32. The low pressure valve 52 is connected between the ports b and c, and the metering pump 30a is connected to the rinse port 38a.
Open to the atmosphere through.

FIG. 5B shows a (B) De-press (depressurizing step) position, in which the high-pressure valve 50 is switched to connect the port to the port, so that the flow path including the sample loop 24 is connected to the measuring pump. Rinse port 3 from 30a
It is open to the atmosphere via 8a. Also, the high pressure valve 50
, The mobile phase continues to flow through the flow path passing through the detection unit 8 via the column 6.

FIG. 6 shows a (C) Load (sample suction) position, in which the low-pressure valve 52 is switched to close the port b connected to the metering pump 30a. The sampling needle 36 is immersed in the sample vial 56 containing the sample, the metering pump 30a is operated, and the sample is sucked into the sampling loop 24 and collected.

FIG. 7 shows the (D) INJ / Purge in (sample injection / metering pump purge) position and the high pressure valve 5
0 is switched to connect the port and the port, and the sampling needle 36 is returned to the injection port 32. As a result, the mobile phase passes through the sampling loop 24, flows through the flow path from the column 6 through the connection point between the sampling needle 36 and the injection port 32, and passes through the detection unit 8, and the sample collected by the sampling loop 24 flows into the column 6. The sample is then separated in column 6. On the other hand, the connection between the port of the high-pressure valve 50 and the connection between the ports a and d of the low-pressure valve 52 allows the rinsing liquid 54 to be sucked into the measuring pump 30a, and the flow path of the measuring pump 30a to be cleaned. Is done.

FIG. 8 shows an (E) Purge out (metering pump purge) position, in which the low pressure valve 52 is switched to connect the ports b and c, and the port a is closed. When the measuring pump 30a is operated, the measuring pump 3
The rinsing liquid sucked into Oa is discharged from the rinsing port 38a. The analysis is continued while the high-pressure valve 50 remains in the state shown in FIG. 7, and the sample components separated in the column 6 are detected by the detection unit 8. Thus, the positions (A) → (B) → (C) → (D) in the order shown in FIGS.
→ By going through the state of (E), a series of analysis operations of sample collection to the sampling loop 24, injection to the column 6, and separation / analysis are automatically performed.

In this embodiment, as another position, there is an (F) Auto Drain (automatic drain) position shown in FIG. In this position, only the port of the high-pressure valve 50 is connected, and the sampling needle 36 is moved to the rinse port 38a. The other ports of the high pressure valve 50 and all ports of the low pressure valve 52 are closed. The mobile phase is sent by the pump unit 2 and is discharged from the high-pressure valve 50 to the rinse port 38a via the sampling loop 24.

The operation of the present invention using the Auto Drain position (F) will be described for the case where the entire flow path is filled with the mobile phase or the mobile phase is replaced. The switching of the high-pressure valve 50 and the low-pressure valve 52 and the movement of the sampling needle 36 are performed at the position (A) Ready →
(B) De-press → (F) Auto Drain → (B) De-press
→ (A) It is controlled to be Ready.

That is, first, the position is at the ready position (A) shown in FIG. Then, it is switched to the Auto Drain position (F) shown in FIG. 9 via the De-press position (B) shown in FIG. Au
In the to drain position (F), the driving of the pump unit 2 is switched to high-speed driving, and the filling or replacement of the mobile phase is performed in a short time. After the mobile phase has been filled or replaced, De-pre
After returning to the Ready position (A) through the ss position (B). Although not shown, both the analysis operation and the mobile phase filling or replacing operation of this embodiment are controlled by the control unit 40 provided in the same manner as in FIG.

[0034]

According to the liquid chromatograph of the present invention, the liquid chromatograph is further provided with a drain port for discharging the liquid discharged from the sampling needle to the outside. When the mobile phase is filled or replaced, the control unit controls the flow path switching valve. Switching and connecting the liquid sending section to the sampling needle via the sampling loop, connecting the sampling needle to the drain port, and performing an operation of switching the driving of the liquid sending section to high-speed driving, and discharging the mobile phase from the drain port. Therefore, not only the motor for the drain valve is not required, but also the drain valve itself is not required, and the filling or replacement of the mobile phase can be automated without increasing the cost of the apparatus.

[Brief description of the drawings]

FIG. 1 is a schematic flow path configuration diagram showing a conventional HPLC.

FIG. 2 is a schematic flow path configuration diagram showing one embodiment.

FIG. 3 is a schematic flow path configuration diagram showing a mobile phase supply portion according to another embodiment.

FIG. 4 is a schematic flow path configuration diagram showing still another embodiment in a Ready position.

FIG. 5 is a schematic flow path configuration diagram showing the same embodiment in a De-press position.

FIG. 6 is a schematic flow path configuration diagram showing the same embodiment in a Load position.

FIG. 7 is a schematic flow path configuration diagram showing the same embodiment in an INJ / Purge in position.

FIG. 8 is a schematic flow path configuration diagram showing the same embodiment in a Purge out position.

FIG. 9 is a schematic channel configuration diagram showing the same embodiment in an Auto Drain position.

[Explanation of symbols]

 Reference Signs List 2 pump unit 4 auto injector 4a auto sampler 6 column 8 detecting unit 10 double plunger reciprocating liquid feed pump 12 primary pump head 16 mobile phase container 18 secondary pump head 20 line filter 22 pressure sensor 24 sampling loop 26 2 Position 6 port valve 28 Three-way valve 30 Metering syringe 30a Metering pump 32 Injection port 34 Sample container 36 Sampling needle 38 Drain port 38a Rinse port 40 Control unit 50 High pressure valve 52 Low pressure valve

Claims (4)

(57) [Claims] 1. A column for separating a sample, a liquid sending section for sending a mobile phase to the column, a sample collected from a sampling needle to a sampling loop, and the collected sample is switched by switching a flow path switching valve. A sample introduction unit for introducing the mobile phase flow path upstream of the column, a detection unit for detecting the sample separated by the column, and a control unit for controlling the operation of the liquid sending unit and the sample introduction unit. In the liquid chromatograph, a drain port for discharging the liquid discharged from the sampling needle to the outside is provided. In addition to the control, the control unit switches the flow path switching valve to set the liquid sending unit to the sampling loop. The sampling needle is connected to the flow path connected to the sampling needle via the Liquid chromatograph control also performs the operation of switching the driving parts in high-speed driving. 2. The flow path switching valve of the sample introduction section is a two-position valve, and a position for connecting the liquid sending section to the column via the sampling loop and a direct connection of the liquid sending section to the column. And a flow path connection is made such that a measuring member for sampling is connected to the sampling loop at a position where the liquid sending section is directly connected to the column. The described liquid chromatograph. 3. The flow path switching valve of the sample introduction section is a three-position valve, and the liquid supply section is connected to the column via the sampling loop, and the liquid supply section is directly connected to the column. And a position in which the liquid sending section is connected to the sampling loop and the upstream of the column is closed, and a measuring member for collecting a sample is provided in a position in which the liquid sending section is directly connected to the column. The liquid chromatograph according to claim 1, wherein a flow path is connected so as to be connected to the sampling loop. 4. A plurality of mobile phase containers accommodating different mobile phases are connected to the suction side of the liquid sending section via respective solenoid valves, and the selection of the mobile phase can be made by opening and closing these solenoid valves. 4. A liquid chromatograph according to claim 1, 2 or 3, which is enabled.