JP4530485B2 - Liquid chromatograph - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a liquid chromatograph, and more particularly to a liquid chromatograph having a sample dilution function.
[0002]
[Prior art]
Conventionally, when the concentration of a sample to be analyzed by a high performance liquid chromatograph is high, a manually diluted sample is used as the sample, or a sample diluted by an automatic sample injection device equipped with a sample dilution function is used. I was analyzing. In an automatic sample injection device equipped with a dilution function, a sample container, a diluent container containing a diluent, and a dilution container for diluting a sample are arranged in a sample rack in which a plurality of sample containers containing samples are arranged. The diluted solution was dispensed into a dilution container to dilute the sample, and then the diluted sample was introduced into the analysis channel.
[0003]
[Problems to be solved by the invention]
However, in manual dilution operations, there are problems such as complicated preparation of many instruments such as dilution containers and weighing instruments necessary for sample dilution, time consuming dilution operations, and unavoidable variations in dilution accuracy. there were.
Automatic sample injection device with dilution function reduces the number of samples that can be analyzed to arrange the dilution containers in the sample rack, may cause sample adsorption in the dilution container, or when the dilution ratio is increased There were problems such as poor dilution accuracy.
Accordingly, an object of the present invention is to provide a liquid chromatograph capable of automatically and accurately diluting a sample without using a dilution container.
[0004]
[Means for Solving the Problems]
In one embodiment of the present invention, a separation column, a liquid feeding portion that sends a mobile phase to the separation column, a sample injection portion for injecting a sample into the mobile phase flow path to the separation column, and a sample component that is eluted from the separation column are detected. A liquid chromatograph equipped with a detector, wherein the sample injection unit includes a sample channel for supplying a sample to be analyzed, a diluent channel for supplying a diluent, a sample channel and a diluent channel. A selection valve for switching and connecting to a common diluted sample flow path, a dilution feeding section for feeding the sample and diluent, a sample loop for temporarily storing a certain amount of sample and diluent, and a sample loop A sample injection valve that switches to and connects to a mobile phase channel or a diluted sample channel, and a sample injection control unit that controls the operation of the sample injection unit. In which the ratio of the diluent and sample introduced into the diluted sample flow path was made to control the switching of the selection valve so as to preset value.
[0005]
By controlling the switching of the selection valve so that the ratio of the sample introduced into the diluted sample channel and the diluent is set to a preset value, the sample is diluted in the diluted sample channel.
[0006]
In another aspect of the present invention, a separation column, a liquid feeding section for sending a mobile phase to the separation column, a sample injection section for injecting a sample into the mobile phase flow path to the separation column, and a sample component eluted from the separation column are detected. In the liquid chromatograph equipped with the detector, the sample injection unit includes a sample flow path for supplying a sample to be analyzed, a sample delivery pump connected to the sample flow path, and a dilute flow for supplying a dilute liquid. A diluting liquid pump connected to the diluting liquid flow path, a confluence section connecting the sample flow path and the diluting liquid flow path to the common diluting sample flow path, and the sample delivery pump and the converging section. An injector for introducing a sample, a sample loop temporarily holding a certain amount of sample and diluent, and switching the sample loop to a mobile phase channel or a diluted sample channel A sample injection valve that continues, and a sample injection control unit that controls the operation of the sample injection unit. The sample injection control unit sets the ratio of the sample introduced into the diluted sample flow path to the dilution liquid to a preset value. Thus, the flow rate of the sample delivery pump and the flow rate of the diluent pump are controlled.
[0007]
By controlling the flow rate of the sample delivery pump and the flow rate of the diluent pump, the ratio of the sample introduced into the diluted sample channel and the ratio of the diluent is set to a preset value, thereby allowing the sample in the diluted sample channel. Dilute.
[0008]
DETAILED DESCRIPTION OF THE INVENTION
The dilution liquid feeding part is a plunger type pump connected to the diluted sample flow path, and the sample injection control part can control the switching of the selection valve in a time-sharing manner within one suction stroke time of the plunger type pump. preferable. As a result, the sample and dilute solution are supplied to the dilute sample channel according to the ratio of the connection time of the selection valve to the sample channel side and the connection time to the dilute channel side determined in consideration of the suction characteristics of the plunger type pump. It can introduce | transduce by the ratio set beforehand, and also a dilution rate.
[0009]
When the dilution liquid feeding part is a plunger type pump connected to the diluted sample flow path, the capacity of the sample loop is preferably an integral multiple of the one-stroke discharge capacity of the plunger type pump. As a result, even if the concentration of the sample is uneven in the diluted sample flow path and the sample loop, the total sample amount introduced into the sample loop is constant.
[0010]
When the dilution liquid feeding part is a plunger type pump connected to the diluted sample flow path, the sample injection control part connects the sample loop to the mobile phase flow path in synchronization with the discharge timing of the plunger type pump. It is preferable to control the switching timing of the sample injection valve. As a result, even if the concentration of the sample is uneven in the diluted sample flow path and the sample loop, the total sample amount introduced into the sample loop is constant.
[0011]
【Example】
FIG. 1 is a flow chart showing one embodiment.
Separation column 9, analytical feed pump 3 for feeding the mobile phase contained in mobile phase container 1 to separation column 9 via mobile phase flow path 5, and sample to mobile phase flow path 5 to separation column 9 A sample injection device 7 for injection and a detector 11 for detecting sample components from the separation column 9 are provided. Reference numeral 13 denotes a personal computer (PC) that controls the operation of the analysis pump 3 and the sample injection device 7 and acquires the detection signal of the detector 11.
The sample is injected from the sample injection device 7 into the mobile phase flow path 5, sent to the separation column 9 by the mobile phase, and separated and eluted. The eluted sample is detected by the detector 11.
[0012]
The sample injection device 7 will be described.
A sample delivery solution container 15 containing a sample delivery solution for delivering a sample and a dilution solution container 21 containing a dilution solution are provided. The sample flow path 17 from the sample delivery liquid container 15 is connected to one port of a selection valve 25 having three ports made of, for example, a Teflon electromagnetic valve. A sample injector 19 for injecting a sample into the sample channel 17 is provided in the middle of the sample channel 17. A diluent flow path 23 from the diluent container 21 is connected to the other port of the selection valve 25. The common port of the selection valve 25 is connected to a diluted sample flow path 27 connected to the suction side of a dilution pump (dilution liquid feeding section) 29 formed of a plunger type pump. The selection valve 25 switches the sample channel 17 and the diluent channel 23 to the diluted sample channel 27 and connects them.
[0013]
The discharge side of the dilution pump 29 is connected via a mixer 31 to a high pressure valve (sample injection valve) 33 having 6 ports. The other ports of the high-pressure valve 33 are connected to the analysis liquid feed pump 3 and the mobile phase flow path 5 between the separation column 9, and the other two ports are fixed amounts of sample and diluent. Are connected to both ends of the sample loop 35, and drain channels 37 are connected to the remaining ports. The high-pressure valve 33 connects the analysis liquid pump 3 and the separation column 9 in the mobile phase channel 5, connects one end side of the sample loop 35 to the diluted sample channel 27 side, and connects the other end side of the sample loop 35. Is connected between the load position (solid line) to the drain channel 37 side, the analytical feed pump 3 of the mobile phase channel 5 and the separation column 9 via the sample loop 35, and the diluted sample channel 27 is drained. It is switched to the injection position (dotted line) connected to the flow path 37 side.
The operations of the selection valve 25, the dilution pump 29 and the high pressure valve 33 are controlled by the sample injection control unit 39. The sample injection control unit 39 is electrically connected to the PC 13.
[0014]
The operation of the sample injection device 7 will be described.
The sample injection control unit 39 sets the high-pressure valve 33 to the injection position (dotted line), connects the selection valve 25 to the sample channel 17 side, and then operates the dilution pump 29 to introduce the sample into the sample channel 17. Thereafter, while operating the dilution pump 29, the selection valve 25 is connected to the sample flow path 17 side for a certain time within one suction stroke time of the dilution pump 29, and the selection valve 25 is switched to dilute liquid flow path 23 side. Repeat the operation to connect to a certain time. As a result, as shown in FIG. 2A, the sample and the diluent are introduced into the diluted sample channel 27 at a predetermined ratio. The ratio of the connection time of the selection valve 25 to the sample channel 17 side and the connection time to the diluent channel 23 side is based on the dilution factor input to the PC 13 in consideration of the suction characteristics of the dilution pump 29. The ratio of the sample introduced into the diluted sample channel 27 and the diluent is determined by the ratio of the connection times.
[0015]
The sample and the diluted solution introduced into the diluted sample channel 27 are guided to the mixer 31 via the dilution pump 29 and mixed (see FIG. 2B). When the sample diluted to a constant concentration reaches the valve position, the high-pressure valve 33 is switched to the load position (solid line), and then the sample mixed with the mixer 31 and the diluted solution are passed through the high-pressure valve 33 through the sample loop. 35. Thereafter, the diluted sample is injected into the mobile phase flow path 5 by switching the high-pressure valve 33 to the injection position (dotted line).
[0016]
In order to clean the inside of the dilution pump 29, the selection valve 25 is connected to the diluent flow path 23 side while the high pressure valve 33 is in the injection position (dotted line), and the dilution pump 29 is operated to perform dilution. The liquid is sucked into the dilution pump 29, and the diluted liquid is discharged from the drain flow path 37 through the mixer 31 and the high pressure valve 33. Thereby, contamination of the sample in the dilution pump 29 can be prevented.
In this way, the sample can be automatically diluted with high accuracy without using a dilution container. Further, the sample can be arbitrarily selected by changing the ratio of the connection time of the selection valve 25 to the sample flow path 17 side and the connection time to the dilution liquid flow path 23 side within one suction stroke time of the dilution pump 29. Can be diluted to a concentration of
[0017]
In the liquid chromatograph of FIG. 1, the volume of the mixer 31 may be reduced if the sample loop 35 has a capacity that is an integral multiple of the one-stroke discharge capacity of the dilution pump 29. That is, even if there is uneven concentration of the sample in the sample and the diluent that have passed through the mixer 31, the total amount of sample introduced into the sample loop 35 is constant. Thereby, the reproducibility of the dilution, and thus the reproducibility of the analysis result can be improved.
[0018]
In the liquid chromatograph of FIG. 1, the volume of the mixer 31 may be reduced by switching the high pressure valve 33 from the load position to the injection position in synchronization with the discharge timing of the dilution pump 29. That is, even if there is uneven concentration of the sample in the sample and the diluent that have passed through the mixer 31, the total amount of sample introduced into the sample loop 35 is constant. Thereby, the reproducibility of the dilution, and thus the reproducibility of the analysis result can be improved.
[0019]
In this embodiment, a plunger type pump is used as a dilution pump, but the present invention is not limited to this, and a liquid feeding pump of another principle such as a peristaltic pump may be used.
Further, the cleaning in the dilution pump 29 is performed using the diluent, but the present invention is not limited to this, and a cleaning liquid container containing the cleaning liquid is provided separately from the diluent container, and the cleaning liquid is A flow path configuration capable of being sucked into the dilution pump 29 may be provided, and the inside of the dilution pump 29 may be cleaned using a cleaning liquid.
[0020]
FIG. 3 is a flow chart showing another embodiment. Parts having the same functions as those in FIG. 1 are denoted by the same reference numerals, and description thereof is omitted.
The mobile phase container 1, the analysis liquid feeding pump 3, the mobile phase flow path 5, the sample injection device 7a, the separation column 9, the detector 11, and the PC 13 are arranged in the same configuration as in FIG.
The sample injection device 7a will be described.
The sample channel 17 and the diluent channel 23 are connected to the diluted sample channel 27 by a three-way tee (merging portion) 45. A sample delivery pump 41 is connected midway between the sample delivery solution container 15 and the sample injector 19 in the sample flow path 17. A diluent pump 43 is connected midway between the diluent container 21 and the selection valve 25 in the diluent channel 23. The diluted sample flow path 27 from the tee 45 is connected to one port of the high pressure valve 33. The sample injection control unit 39 controls the operation of the high-pressure valve 33, the sample delivery pump 41, and the diluent pump 43.
[0021]
The operation of the sample injection device 7a of this embodiment will be described.
After the high-pressure valve 33 is set to the load position (solid line), the sample injection control unit 39 operates the sample delivery pump 41 and the diluent pump 43 at respective preset flow rates. The sample introduced from the injector 19 is transported to the tee 45 where it is diluted with the diluent from the diluent channel 23 and introduced into the diluted sample channel 27. As a result, the sample and the diluent are introduced into the diluted sample channel 27 at a predetermined ratio.
[0022]
The sample and the diluent introduced into the diluted sample channel 27 are introduced into the sample loop 35 via the high pressure valve 33.
In this way, the sample can be automatically diluted without using a dilution container. Furthermore, since the sample can be introduced into the sample loop 35 without remaining in the diluted sample flow path 27, a washing step after the sample is injected into the analysis flow path 5 is not necessary.
Further, the sample can be diluted to an arbitrary concentration by changing the flow rate of the sample delivery pump 41 and the flow rate of the diluent pump 43.
[0023]
【The invention's effect】
In one aspect of the present invention, the sample injecting section switches a sample flow path for supplying a sample to be analyzed, a diluent flow path for supplying a diluent, a sample flow path and a diluent flow path to switch a common dilution path. A selection valve connected to the sample flow path, a dilution feeding section for feeding the sample and the diluent, a sample loop temporarily storing a certain amount of the sample and the diluent, and the sample loop as a mobile phase flow path or A sample injection valve for switching and connecting to the diluted sample flow path and a sample injection control section for controlling the operation of the sample injection section are provided. Since the switching of the selection valve is controlled so that the value becomes a preset value, the sample can be diluted in the diluted sample flow path, and a dilution container is used. It can be diluted highly accurately automatically samples without and.
[0024]
The dilution liquid feeding part is a plunger type pump connected to the diluted sample flow path, and the sample injection control part performs time-sharing control of switching of the selection valve within one suction stroke time of the plunger type pump. In this case, the sample and diluent are supplied to the diluted sample channel according to the ratio of the connection time of the selection valve to the sample channel and the connection time to the diluent channel determined in consideration of the suction characteristics of the plunger type pump. It can introduce | transduce by the ratio set beforehand, and also a dilution rate.
[0025]
When the dilution pump is a plunger type pump connected to the diluted sample flow path, the volume of the sample loop should be an integral multiple of the one-stroke discharge capacity of the plunger pump. Even if the concentration of the sample is uneven in the sample loop, the total amount of sample introduced into the sample loop is constant, so that the reproducibility of dilution and hence the reproducibility of the analysis result can be improved.
[0026]
When the dilution liquid feeding part is a plunger type pump connected to the diluted sample flow path, the sample injection control part connects the sample loop to the mobile phase flow path in synchronization with the discharge timing of the plunger type pump. If the sample injection valve switching timing is controlled, the total sample amount introduced into the sample loop will be constant even if the concentration of the sample is uneven in the diluted sample flow path and sample loop. The reproducibility of dilution, and thus the reproducibility of analysis results can be improved.
[0027]
In another aspect of the present invention, the sample injection section includes a sample flow path for supplying a sample to be analyzed, a sample delivery pump connected to the sample flow path, a dilution liquid flow path for supplying a diluent, Sample is introduced between the diluent pump connected to the diluent flow path, the confluence section connecting the sample flow path and the diluent flow path to the common diluted sample flow path, and the sample delivery pump and confluence section Operation, a sample loop temporarily storing a certain amount of sample and diluent, a sample injection valve for switching the sample loop to a mobile phase flow path or a diluted sample flow path, and operation of the sample injection section A sample injection control unit that controls the sample injection control unit so that the ratio of the sample introduced into the diluted sample flow path and the diluted solution becomes a preset value. Since the flow rate of the delivery pump and the flow rate of the dilution liquid pump are controlled, the ratio of the sample and the dilution liquid introduced into the diluted sample flow path can be determined. The cleaning process after injecting into the analysis channel is not necessary.
[Brief description of the drawings]
FIG. 1 is a flow chart showing an embodiment.
FIGS. 2A and 2B are schematic views showing a state of a sample and a diluted solution introduced into a diluted sample flow channel in the same example, where FIG. 2A shows before mixing, and FIG. 2B shows after mixing.
FIG. 3 is a flow path configuration diagram showing another embodiment.
[Explanation of symbols]
DESCRIPTION OF SYMBOLS 1 Mobile phase container 3 Liquid feed pump for analysis 5 Mobile phase flow path 7, 7a Sample injection device 9 Separation column 11 Detector 13 Personal computer (PC)
15 Sample delivery liquid container 17 Sample flow path 19 Sample injector 21 Dilution liquid container 23 Dilution liquid flow path 25 Selection valve 27 Dilution sample flow path 29 Dilution pump 31 Mixer 33 High pressure valve 35 Sample loop 37 Drain flow path 39 Sample injection control section 41 Sample delivery pump 43 Diluent pump 45 3-way tee

Claims (5)

Liquid chromatography equipped with a separation column, a liquid feeding section for sending the mobile phase to the separation column, a sample injection section for injecting the sample into the mobile phase flow path to the separation column, and a detector for detecting the sample components eluted from the separation column In the graph,
The sample injection section switches a sample flow path for supplying a sample to be analyzed, a diluent flow path for supplying a diluent, and switching the sample flow path and the diluent flow path to a common diluted sample flow path. A selection valve to be connected; a dilute liquid supply section that is provided in the dilute sample flow path to send a sample and dilute liquid; and a dilute sample solution consisting of the sample and dilute liquid sent from the dilute liquid feed section A sample loop that temporarily stores an amount, and the dilute sample solution stored in the sample loop as it is by switching and connecting the sample loop to the mobile phase channel or the diluted sample channel. A sample injection valve to be introduced into the sample injection control unit, and a sample injection control unit for controlling the operation of the sample injection unit,
The liquid injection chromatograph, wherein the sample injection control unit controls switching of the selection valve so that a ratio between a sample introduced into the diluted sample flow path and a diluted liquid becomes a preset value. The dilution feeding section is a plunger type pump connected to the diluted sample flow path,
The liquid chromatograph according to claim 1, wherein the sample injection control unit performs time-sharing control of switching of the selection valve within one suction stroke time of the plunger pump.   The liquid chromatograph according to claim 2, wherein the volume of the sample loop is an integral multiple of the one-stroke discharge capacity of the plunger-type pump.   The said sample injection control part controls the switching timing of the said sample injection valve so that the said sample loop may be connected to the said mobile phase flow path synchronizing with the discharge timing of the said plunger type pump. Liquid chromatograph. Liquid chromatography equipped with a separation column, a liquid feeding section for sending the mobile phase to the separation column, a sample injection section for injecting the sample into the mobile phase flow path to the separation column, and a detector for detecting the sample components eluted from the separation column In the graph,
The sample injection unit includes a sample channel that supplies a sample to be analyzed, a sample delivery pump connected to the sample channel, a diluent channel that supplies a diluent, and a diluent channel. A sample is introduced between the connected dilution liquid pump, the merging portion connecting the sample flow path and the dilution liquid flow path to a common diluted sample flow path, and the sample delivery pump and the merging section. An injector, a sample loop temporarily storing a fixed amount of a diluted sample solution consisting of a sample and a diluent sent from the junction , and the sample loop is switched to the mobile phase channel or the diluted sample channel a sample injection valve for introducing the diluted sample solution contained in the sample loop to directly the mobile phase flow path by connecting said sample And a sample injection control part for controlling the operation of the join the club,
The sample injection control unit controls the flow rate of the sample delivery pump and the flow rate of the diluent pump so that the ratio of the sample and the diluent introduced into the diluted sample flow path becomes a preset value. A liquid chromatograph characterized by

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