JP4480808B2 - Liquid feeding method and apparatus such as liquid chromatograph - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a liquid feeding method and apparatus such as a liquid chromatograph.
[0002]
[Prior art]
In high-performance liquid chromatography that is widely used as a means for separation and analysis, a pump for feeding the eluent is a very important element for ensuring the stability of the chromatograph. Since the syringe-type pump is a screw-type feeding method using a motor, high pressure can be easily obtained and pulsation is small, but the amount of liquid fed is limited by the volume of the cylinder, and continuous analysis is difficult. In addition, since the plunger type pump is a system that sends liquid according to the reciprocating motion of the piston, the capacity in the pump is small, and liquid can be sent continuously, but pulsation is likely to occur due to pressure fluctuation.
[0003]
In order to improve this point, a double-plunger method using a plurality of plungers is currently used in the most common high performance liquid chromatography. The flow rate can be adjusted by changing the stroke length of the plunger or changing the number of reciprocations of the plunger. As specific control methods, there are known a method in which a certain position in the operating range of the plunger is set as a designated position, a stroke length is determined based on a moving distance from the specified position, a method in which the number of rotations of the motor is changed, and the like.
[0004]
One of these is a liquid feed pump described in Japanese Patent Publication No. 4-61198. This consists of a pressure pump that can apply compression pre-pressure and a metering pump that discharges the liquid from the pressure pump to the outside, detects the pressure on the output side of the metering pump, and the pressure in the metering pump chamber is When switching to the discharge process, the liquid discharged from the pressurized pump chamber to the metering pump chamber is pressurized so as to be the same as the detected pressure.
This makes it possible to secure a set flow rate for any type of liquid without the need for a refill curve for the pressure-resistant flow rate that is suitable for the liquid to be delivered, and no correction curve is required for gradient elution. It is said that it will be possible to secure.
[0005]
In recent years, apart from analysis using a general-purpose column, semi-micro and micro analysis using a column with a smaller inner diameter has been attracting attention. These analyzes require less solvent for the eluent and its waste solution compared to general-purpose analysis, so there is less concern about the impact on the analyst and the environment, and because the dilution rate of the introduced sample is small, it is highly sensitive. Since analysis becomes possible and connection with a detector that cannot introduce a large amount of liquid becomes easy, it has begun to be used for analysis of trace samples, particularly biological samples.
[0006]
[Problems to be solved by the invention]
In this case, a minute flow rate is realized by lowering the moving speed of the plunger and moving it slowly. In addition, in order to improve the solvent composition follow-up performance during so-called Gungent analysis and the liquid feed stability during isocratic analysis by changing the solvent composition according to the time, the stroke length of the plunger is analyzed. It is made to change by.
For example, in the case of low pressure gradient analysis, if the stroke length is long, the followability of the gradient of the solvent composition becomes extremely poor, and the reproducibility of the resulting chromatogram peak may be lost at all. Conversely, it is possible to set a long stroke length, pass one composition solvent through each of the two plungers, and perform a high pressure gradient analysis with one double plunger pump.
[0007]
In the case of isocratic analysis, more stable liquid feeding and higher liquid feeding accuracy can be obtained by changing the stroke length according to the flow rate, pressure or the type of solvent. In order to change the stroke length of the plunger during operation, it is necessary to temporarily move the plunger to a specified position in the operating range and newly operate it based on that position.
[0008]
Currently, the flow rate suitable for a liquid chromatograph using a general purpose column is about 1 ml / min. When the stroke volume of the liquid feed pump is 100 μl, a time of 0.1 min is required for one stroke. With this flow rate, the time for moving the plunger once is sufficiently small so as not to affect the analysis, and the gradient analysis can be sufficiently followed.
[0009]
On the other hand, if the pump is used for analysis using a microcolumn and the flow rate is set to 1 μl / min, a time of 100 min is required for one stroke. Of course, the time for moving the plunger once becomes as long as that, and not only for gradient analysis but also for other condition changes.
[0010]
Therefore, it is conceivable to move the plunger at high speed and force it to the specified position only when changing the analysis conditions, but since a high-resistance separation column is connected downstream of the pump. During the time of movement, the pressure of the entire system suddenly increases, and the allowable pressure of the column and other devices may be exceeded or adversely affected.
[0011]
On the other hand, Japanese Patent Application Laid-Open No. 6-324025 discloses an automatic drain valve that allows a large amount of liquid to be rapidly fed and fed. The drain valve has a solvent introduction port, a solvent outlet, and a drain flow path in one block, and is intended to reduce the dead volume by rotating the switching seal driven by a motor. The structure of switching to the solvent outlet and the drain flow path through the switching groove formed in the switching seal requires a high level of processing technology and the valve structure is complicated. Cost is also high.
[0012]
An object of the present invention is to obtain a method and a configuration that enable a high-speed movement of the plunger when the plunger stroke is changed according to the analysis conditions and that the system pressure at that time hardly increases. In particular, to achieve the object in microanalysis using semi-micro / micro columns. In addition, conventionally, one purpose is to manually open the drain valve and communicate with the discharge flow path at a high flow rate in order to replace the solvent, clean the pump, and remove air mixed in the pump head. Or the cleaning solution is fed. However, the user may manually open the drain valve when the system pressure has not dropped to a safe value. In that case, there is a possibility that the column may be damaged by sudden pressure fluctuation. In order to prevent such troubles, first, a safe pressure is set for the column, and a command to send liquid at a high flow rate is issued by key operation. At that time, from the time when the system pressure detected by the pressure sensor drops below the set pressure, the automatic drain valve automatically communicates with the discharge flow path by the signal sent from the control unit, and the solvent is replaced quickly. To obtain a configuration that can automatically perform operations such as cleaning the pump and removing air mixed in the pump head. Another object is to achieve miniaturization and low dead volume by a simple automatic drain valve of the mechanism, and to save space, reduce cost, and obtain convenience by automatic control.
[0013]
[Means for Solving the Problems]
For this reason, in the present invention, first, the pressure of the mobile phase is sensed by the pressure sensor, and when the analysis conditions are changed, the mobile phase is discharged from the discharge channel when the pressure drops below the set pressure. At the same time, the controller moves the plunger of the pump to a designated position at a high speed via the pressure signal , and secondly, the connection flow path and the discharge flow path connected to the injector are connected to the drain body. A pressure sensor that senses the pressure of the mobile phase is provided in addition to a communication state through the flow path between the dampers and the connection flow path to the pump, and when the signal from the pressure sensor drops below the set value, It has a control part for moving a plunger to a specified position at high speed, and discharging a mobile phase from this discharge channel .
[0014]
DETAILED DESCRIPTION OF THE INVENTION
The present invention will be described below with reference to an embodiment shown in the drawings.
FIG. 1 shows a flow channel system of a liquid chromatograph according to an embodiment of the present invention. In the figure, reference numeral 2 denotes a pump, and in particular, a micro flow rate pump, for example, a pump capable of sending a mobile phase in a flow rate range of 0.01 to 500 μl / min is used. An automatic drain valve 3 described in detail below is connected to the outlet side. Here, the mobile phase refers to various solvents and cleaning solutions.
[0015]
The automatic drain valve 3 is formed with a connection flow path 21 to the injector 5 on one side of the drain body 10 and a discharge flow path 14 on the other side. The connection flow path 21 is connected to the connection port 51 of the injector 5, and is connected to the column 6 via the sample loop and the connection port 52 at the connection ports 53 and 56. 7 is a detector connected to the column 6, and one is connected to the waste liquid tank 4. A control unit 9 controls the pump 2, the automatic drain valve 3, and the injector 5. The chromatographic data processing device 8 connected to the detector 7 is also controlled by the control unit 9.
[0016]
【Example】
2 to 5 show an embodiment of the automatic drain valve 3. The automatic drain valve 3 includes a screw 15 that can freely enter and exit a drain body 10 fixed to a housing or the like that houses a pump, a sliding mechanism 16 that linearly moves the screw 15, and a motor 19 that is fixed to the housing. Yes. The screw 15 is screwed into a screw 102 provided in a guide 101 provided in the drain body 10 by the screw 151 so as to be freely screwed out. A ring 152 is fitted into the screw 15 at an appropriate place to maintain watertightness. A stop plug 153 is provided at the tip of the screw 15, and it is convenient to form it with a polymer having some elasticity.
[0017]
A communication hole 103 communicating with the connection flow path 20 of the pumps 2 and 2 is formed at the tip of the guide 101. The end of the communication hole 103 is preferably formed in a tapered shape so as to engage with the stop plug 153, and the rear end communicates with the connection flow path 20. The discharge channel 14 is formed in the drain body 10, and the tip thereof communicates with the tip of the guide 101. Further, the drain body 10 includes a connection flow path 21 connected to the injector 5 (or an autosampler), a damper 11 which is a unit for reducing the pulsating flow of the pump 2, and a pressure sensor 12 which detects a discharge pressure of the pump 2. Are integrally formed.
[0018]
In this configuration, a cavity 104 is formed on one side of the drain body 10, for example, an opposing surface into which a screw 15 is screwed, and a damper 11 is provided via a diaphragm 13. The periphery of the diaphragm 13 is fixed to the drain body 10, and faces the opening or opening groove 201 of the connection flow path 20 to the pump 2 and the opening 210 of the connection flow path 21. This damper 11 is constituted by a bag body in which a compressible liquid is enclosed, and a diaphragm 13 is attached to the rear end.
[0019]
Next, the advance and retreat of the screw 15 will be described. A sliding mechanism 16 is provided on the drive shaft of the motor 19 or its extension shaft 191 and is engaged with the screw 15. The sliding mechanism 16 is provided with a sliding guide 161 that allows the screw 15 to enter and exit, and the sliding guide 161 is provided with a groove 162. FIG. 4A shows a state in which the pin 154 is overhanged and engaged with the groove 162. Further, in order to reduce friction between the pin 154 and the groove 162, a steel ball 155 can be embedded between the pin 154 and the groove 162, and a guide groove 163 of the ball 155 can be provided in the groove 162 (FIG. 4B). Further, the pin 154 may be provided with a bearing 156 at a portion corresponding to the groove 162 (FIG. 4C). A disc-shaped sensor plate 18 is provided at the rear end of the sliding mechanism 16, and a positioning sensor 17 is provided at the end of the sensor plate 18. As the positioning sensor 17, various known sensors such as a strobe and a photo interrupter can be used.
[0020]
The pump 2 includes a known cylinder and a plunger, and a sensor is attached to the rear end of the plunger drive unit to sense the movement position of the plunger, and the control is performed by the control unit 9 using a pulse signal of a stepping motor or the like. It is recommended that the automatic drain valve 3 and the injector 5 are also connected to the control unit 9 and configured to be controlled by each. The control unit 9 controls the connection based on the system pressure signal and the key operation command.
[0021]
Next, the operation will be described.
During the analysis, the liquid sent from the mobile phase tank 1 by the pump 2 is sent to the empty space 104 through the opening or open groove 201 through the connection flow path 20 to the pump of the automatic drain valve 3. Then, the mobile phase enters the connection channel 21 through the opening 210 while pushing the diaphragm 13, the connection channel 21 communicates with the injector 5, and the mobile phase flows into the connection channel 21.
[0022]
At this time, the force with which the mobile phase presses the diaphragm 13 is perceived by the pressure sensor 12 via the damper 11 and transmitted to the control unit 9.
When the flow rate is changed by a key operation or a set program through the control unit 9, a signal sent to the control unit 9 from the time when the system pressure detected by the pressure sensor 12 falls below the set pressure. Thus, the discharge flow path 14 is automatically opened, and the mobile phase is discharged from the discharge flow path 14 having a low resistance, so that the system pressure hardly increases. The opening of the discharge channel 14 will be described in detail. The motor 19 is rotated by a signal from the control unit 9 and the sliding mechanism 16 provided on the shaft 191 is rotated. By this rotation, the screw 15 is rotated via the pin 154 engaged with the groove 162 of the sliding mechanism 16. The screw 15 is guided and retracted by a screw 151 screwed into the screw 102. The backward movement of the screw 15 is a mold in which the rear part advances to the sliding guide 161, and the pin 154 moves in the groove 162. For this reason, the stop plug 153 at the tip of the screw 15 is detached from the rear end taper of the communication hole 103. Therefore, the communication hole 103 communicating with the connection flow path 20 is opened and communicates with the discharge flow path 145 via the guide 101.
[0023]
On the other hand, the rotation of the motor 19 senses the rotation of the sensor plate 18 provided in the sliding mechanism 16 by the positioning sensor 17 and sends the signal to the control unit 9 to be controlled. Stopped. On the other hand, in the pump 2, the motor of the drive unit moves the plunger to a designated position at high speed. Of course, since the connection flow path 21 connected to the injector 5 at this time has a high resistance, the mobile phase flows to the discharge flow path 14 having a low resistance. When the plunger is moved to the designated position, the automatic drain valve 3 closes the discharge flow path 14 according to the signal sent from the control unit 9, and the pump 2 automatically strokes according to the set flow rate. Pump the liquid.
[0024]
【The invention's effect】
As described above, according to the first aspect of the present invention, the pressure of the mobile phase is sensed by the pressure sensor, and when the analysis condition is changed, the mobile phase is removed from the discharge channel when the pressure drops below the set pressure. The pump plunger is moved to the specified position at high speed by the control unit via the pressure signal at the same time, so the plunger stroke length of the pump can be changed automatically and quickly with an extremely simple method and easy operation. In addition, it is possible to prevent the liquid chromatograph from adversely affecting the entire system, such as a rapid increase in the pressure of the entire system, and applying an excessive pressure to the column and other devices. In addition, the automatic and quick change of the stroke length of the plunger of the pump can shorten the stable control time of the liquid chromatograph system, and stable and accurate liquid feeding can be achieved by changing the plunger stroke. In particular, the above-mentioned effects are particularly remarkable in microanalysis using semi-micro and micro columns.
[0025]
According to claim 2, the connection flow path and the discharge flow path connected to the injector are brought into communication with each other via the flow path between the drain body and the damper and the connection flow path to the pump. A pressure sensor that senses the pressure, and when the signal from the pressure sensor falls below the set value, the pump plunger is moved to a specified position at a high speed, and the mobile phase is discharged from the discharge flow path. In addition to the same effects as in claim 1, the plunger stroke can be freely changed according to the change in the solvent composition during the gradient analysis, the flow rate of the isocratic analysis, the pressure, and the type of the solvent. Trace analysis using semi-micro and micro columns can be easily performed with high accuracy.
[Brief description of the drawings]
FIG. 1 is a schematic diagram showing a flow system of a liquid chromatograph according to an embodiment of the present invention. FIG. 2 is a schematic sectional view showing an embodiment of an automatic drain valve. FIG. 3 is a sectional view taken along line AA in FIG. 4A is a schematic view showing an embodiment of the sectional view taken along the line BB of FIG. 2; FIG. 4B is a schematic view showing another embodiment of the sectional view taken along the line BB of FIG. FIG. 5 is a schematic diagram showing another embodiment of the cross-sectional view taken along the line B. FIG. 5 is an enlarged schematic diagram of a part of FIG.
DESCRIPTION OF SYMBOLS 1 Mobile phase tank 2 Pump 3 Automatic drain valve 4 Waste liquid tank 5 Injector 6 Column 7 Detector 8 Chromatography processor 9 Control part 10 Drain body 11 Damper 12 Pressure sensor 13 Diaphragm 14 Discharge flow path 15 Screw 16 Sliding mechanism 17 Positioning sensor 18 Sensor plate 19 Motor 20 Connection flow path 21 Connection flow path

Claims (2)

The pressure of the mobile phase is detected by the pressure sensor, and when the analysis conditions are changed, the mobile phase is discharged from the discharge flow channel when the pressure drops below the set pressure, and at the same time, the control unit via the pressure signal A liquid feeding method such as a liquid chromatograph , wherein the pump plunger is moved to a designated position at high speed . The connection flow path and the discharge flow path connected to the injector are in communication with each other via the flow path between the drain body and the damper and the connection flow path to the pump, and a pressure sensor for sensing the pressure of the mobile phase is provided. A liquid having a control unit for moving the plunger of the pump at a high speed to a specified position and discharging the mobile phase from the discharge channel when the signal from the pressure sensor falls below a set value. Liquid delivery equipment such as chromatographs .

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