JP2000249694A - Liquid chromatograph separation equipment - Google Patents

Abstract

PROBLEM TO BE SOLVED: To recognize the generation of blocking by providing a flow-rate detection means in a switchable second channel being provided on an analysis channel. SOLUTION: A sample solution that is subjected to constituent separation by a column 3 separately flows to an analysis channel 8 and a fraction collector channel 9 with a specific split ratio by a splitter 4. A sample solution flowing into the analysis channel 8 passes through a first channel 16 of a 6-port valve 15 and reaches a mass spectrometer 6, thus detecting a sample signal. In a certain amount of time, a switching valve in the fraction collector 7 is switched to sample a target constituent. For checking the blocked state during sampling, the 6-port valve 15 is switched to feed a solution for a mobile phase only. By measuring the rate of flow that actually runs by a flowmeter 17 at this time, the presence or absence of blocking can be verified. When no specific flow rate has been reached, failure can be easily determined by displaying an error on a display.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a liquid chromatograph fractionating apparatus, and more particularly, to a liquid chromatograph fractionating apparatus using a mass spectrometer as a detector.

[0002]

2. Description of the Related Art One of the applied techniques of liquid chromatography (hereinafter, referred to as LC) is to provide a fraction collector (hereinafter, referred to as FRC) at a stage subsequent to an LC channel to selectively capture only target components contained in a sample. There is a liquid chromatograph fractionator that is designed to collect. Normally, liquid chromatographs are equipped with pumps, sample injectors, columns,
It includes a detector, a fraction collector, and a system controller that controls the fractionation operation. When the peak of the target component is detected by the detector, the switch valve is driven when the peak component reaches the switch valve of the fraction collector, and the target component is collected. As this detector, an ultraviolet-visible light detector (UV detector) is generally used, and the sample solution flowing through a flow cell provided at the subsequent stage of the column is used as the detector.
It is monitored by a V detector.

In recent years, mass spectrometers have been used instead of UV detectors to perform higher-performance fractionation. FIG. 3 shows L using a conventional mass spectrometer as a detector.
1 shows a configuration of a CMS sorting apparatus. In the figure, 1 is a liquid feed pump for supplying a mobile phase, 2 is a sample injector, 3 is a column for separating components, 4 is a splitter, 5 is a system controller, 6 is a mass spectrometer as a detector, 7 is A fraction collector for fractionation, 8 is an analysis flow path, 9 is a fraction collector flow path, and 10 is a control unit composed of a personal computer. The feature of the fractionating device using the mass spectrometer 6 as a detector is that the column 3 is divided into an analysis channel 8 connected to the mass spectrometer and a fraction collector channel 9 connected to the fraction collector at the subsequent stage. The point is that the splitter 4 is provided. That is, when performing a normal fractionation operation, the flow rate of the mobile phase is maintained at about several tens ml / min.
The maximum flow rate that can be passed through the mass spectrometer is 2 ml /
Since the flow rate is as small as about one minute, only a part of the sample solution eluted from the column 3 is branched to flow to the mass spectrometer 6. Further, since the mass spectrometer 6 ionizes and analyzes the sample solution, it is difficult to recover the sample solution after analysis. Therefore, it is necessary to use only a part of the sample solution for analysis and to use the remaining solution for recovery. is there.

[0004]

[0005] In the LCMS fractionating apparatus, the splitter is provided at the subsequent stage of the column as described above. However, since a large amount of sample is continuously flowed in the case of fractionation, "clogging" may occur on the analysis flow path side (especially the MS probe piping section) having a small pipe inner diameter. However, even if clogging occurs, only the split ratio changes and the pump pressure does not rise,
The operator cannot recognize that the clogging has occurred, and as a result, a problem has arisen that the operation timing of the switching valve of the fraction collector is erroneous.

Accordingly, an object of the present invention is to prevent erroneous sorting work by making it possible to recognize that clogging has occurred with an MS probe or the like.

[0006]

SUMMARY OF THE INVENTION In order to solve the above-mentioned problems, a liquid chromatographic fractionating apparatus according to the present invention is provided with a splitter at a position subsequent to a column for performing component separation, so that a liquid flowing through a mass spectrometer can be analyzed. In a liquid chromatograph fractionating apparatus that is branched into a flow path and a fraction collector flow path flowing to a fraction collector, a second flow path that can be switched by a valve operation is provided on the analysis flow path, and the second flow path is provided in the second flow path. It is characterized by having flow rate detecting means.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION In the liquid chromatograph fractionating apparatus of the present invention, when it is desired to check whether the analysis flow path is clogged, the analysis flow path is switched to the second flow path by operating a valve. The second flow path has a flow rate detecting means, which makes it possible to determine the presence or absence of clogging by measuring the flow rate flowing through the second flow path. Since the second flow path is connected only when the flow rate is checked, the sample flows through the normal analysis flow path during analysis. Therefore, a dead volume does not occur and the peak shape is not affected.

Hereinafter, the present invention will be described with reference to the drawings. FIG.
1 is a liquid chromatograph fractionating apparatus according to one embodiment of the present invention. In the figure, the same parts as those in FIG. In this apparatus, an analysis flow path 8 between the splitter 4 and the mass spectrometer 6 is provided.
Is provided with a 6-port valve 15 for switching the flow path. The 6-port valve 15 can switch between a first flow path 16 that connects straight to the splitter mass spectrometer and a second flow path 18 with a flow meter 17 interposed in the middle of the flow path. That is, in the first state, the splitter 4 and the mass spectrometer 6 are connected straight by the first flow path 16 as shown in FIG.
On the 8th side, a syringe pump 21 and a drain 2 provided separately
2 and the channel is washed by driving the syringe pump 21. On the other hand, in the second state, the splitter 4 and the mass spectrometer 6
Is connected, and the flow rate can be measured by the flow meter 17.

Next, the operation will be described. At the time of fractionation, the 6-port valve 15 is set to the first state shown in FIG. 1, and the sample solution is introduced. The sample solution separated by the column 3 flows into the analysis channel 8 and the fraction collector channel 9 by the splitter 4 at a predetermined split ratio. The sample solution flowing into the analysis channel 8 is a 6-port valve 1
5 to the mass spectrometer 6 where the sample signal is detected. By switching the switching valve in the fraction collector 7 with a certain delay after the detection of the sample signal, the target component is fractionated. The adjustment of the split ratio and the delay time is performed by a combination of the inner diameter and the length of the pipe.
The pipe on the side has a smaller diameter (inner diameter 0.13 mm to 0.075 m
m) and the length is shortened so that most of the sample solution flows to the fraction collector channel 9 side. Therefore, the piping is easily clogged on the analysis channel side with sample deposits, minute dust generated from the injector, and the like. If the flow path is clogged, the delay time changes, so that accurate sorting cannot be performed. Therefore, since it is necessary to periodically check for clogging, the clogging state is checked between sortings. In this case, the 6-port valve 15 is set to the second state shown in FIG. In the second state, a solution containing only the mobile phase is sent as a standard sample. At this time, by measuring the flow rate actually flowing by the flow meter 17, the presence or absence of clogging can be confirmed.
If the abnormality of the flow rate is detected, if the predetermined flow rate is not reached, an error is displayed on a display unit of a control unit (not shown) so that the abnormality can be easily known. In this embodiment, the flow rate is measured using a flow meter. However, the flow rate can be measured substantially by using a pressure sensor instead of the flow meter.

[0010]

As described above, in the apparatus of the present invention, the second flow path which can be switched to the analysis flow path is provided, and the second flow path is provided with the flow rate measuring means. Can be measured. In the apparatus of the present invention, since the flow rate measuring means is not provided directly in the analysis flow channel, no dead volume occurs and no analysis peak is caused.

[Brief description of the drawings]

FIG. 1 is a configuration diagram of a liquid chromatograph fractionating apparatus according to one embodiment of the present invention.

FIG. 2 is a diagram showing a state when measuring a flow rate in the apparatus of FIG. 1;

FIG. 3 is a configuration diagram of a conventional liquid chromatograph fractionating apparatus.

[Explanation of symbols]

 4: Splitter 6: Mass spectrometer 7: Fraction collector 8: Analysis flow path 9: Fraction collector flow path 15: 6-port valve 16: First flow path 17: Flow meter 18: Second flow path

Claims (1)

[Claims] 1. A liquid chromatograph fractionating apparatus in which a splitter is provided at a position subsequent to a column for performing component separation so as to branch into an analysis channel flowing through a mass spectrometer and a fraction collector channel flowing through a fraction collector. 2. The liquid chromatograph fractionating apparatus according to claim 1, wherein a second flow path that can be switched by a valve operation is provided on the analysis flow path, and a flow rate detection unit is provided in the second flow path.