WO2016147415A1

WO2016147415A1 - Control device for chromatograph

Info

Publication number: WO2016147415A1
Application number: PCT/JP2015/058377
Authority: WO
Inventors: 恭章中村; 禎宏早川
Original assignee: 株式会社島津製作所
Priority date: 2015-03-19
Filing date: 2015-03-19
Publication date: 2016-09-22
Also published as: JPWO2016147415A1; JP6361816B2

Abstract

The objective of the present invention is to provide a chromatograph system 100 with which it is easy for a target component and an impurity component contained in a sample to be measured simultaneously. The chromatograph system 100 according to the present invention is provided with: a single-wavelength measuring unit which causes a chromatograph to operate in a single-wavelength measuring mode (one-wavelength mode); a multiple-wavelength measuring unit which causes the chromatograph to operate in a multiple-wavelength measuring mode (two-wavelength mode); and a mode switching unit which switches between the single-wavelength measuring mode and the multiple-wavelength measuring mode in accordance with a chromatogram time range. Further, the chromatograph system is also provided with: a time program creating unit 37 for creating a time program which causes the chromatograph to operate in one of these modes in accordance with a chromatogram time span; and a time program executing unit 38 which causes the chromatograph to operate in accordance with the time program. The program for causing the chromatograph to operate in these modes is stored in a storage unit 32.

Description

Chromatographic control device

The present invention relates to a chromatograph, and more particularly to a chromatographic control device for controlling the operation thereof.

As shown in FIG. 1, the liquid chromatograph 10 is separated by a separation column 11, a liquid feed pump 13 for feeding the mobile phase 12 to the separation column 11, an injector 14 for injecting a sample into the mobile phase, and the separation column 11. And a detector 15 for detecting components in the sample. In addition, after detecting a component, it is also possible to isolate | separate and take out each component (sorting).

As shown in FIG. 2, the detector 15 includes a sample cell 24 that contains a sample eluted from the separation column 11, a light source 21 that generates light of a predetermined wavelength for irradiating the sample cell 24, a spectroscopic element 22, a spectroscopic element The divided optical system 23 that divides the emitted light into the irradiation light to the sample cell 24 and the reference light that does not pass through the sample cell 24, the intensity of the measurement light that has passed through the sample cell 24, and the reference light that does not pass through the sample cell 24 are measured It consists of a light receiving unit 25 and the like, and by measuring the absorbance (absorbance spectrum) for each wavelength of the sample, the component in the sample is specified, or by measuring the absorbance of light of the wavelength corresponding to the target component in the sample The concentration of the target component is detected.

Many substances have light-absorbing properties especially in the ultraviolet region. Therefore, impurity measurement can also be performed by measuring the ultraviolet region simultaneously with the absorption wavelength of the target component. Even if the separation of the components in the separation column 11 is sweet, if there is a difference in the absorption wavelength between the components, the separated peak data can be obtained for each wavelength, and the separated analysis can be performed. Therefore, a method of simultaneously measuring a plurality of wavelengths (hereinafter referred to as “multi-wavelength measurement”, and a method using only one wavelength as described above is referred to as “single-wavelength measurement”) is also performed. .

For multi-wavelength measurement, as shown in FIG. 3A, a sample cell is irradiated with multi-wavelength light, and a multi-wavelength detector (photodiode array) 26 in which a plurality of photo-detecting elements such as photodiodes are arranged is used to measure a plurality of wavelengths. And a method of measuring a plurality of wavelengths substantially simultaneously by switching a plurality of wavelengths in a short time. In the latter type, as shown in FIG. 3B, a plurality of light sources (LEDs in FIG. 3B) 21a and 21b are prepared and switched, and as shown in FIG. 3C, there is only one light source 21. There is a method of switching the wavelength by rotating the spectroscopic element 22. Since the method of moving the spectroscopic element 22 (FIG. 3C) is difficult to switch the wavelength quickly, high-speed sampling cannot be performed. Therefore, it is not suitable for high-speed analysis with a narrow chromatographic peak width. However, in the case of low / medium-speed analysis, since the apparatus configuration is simple, multi-wavelength detection having the above-described merit can be easily performed.

JP 04-038446

Many substances have an absorption wavelength in the ultraviolet region. Therefore, in the case of the impurity measurement or simultaneous analysis in which a sample containing a plurality of components is analyzed all at once, the measurement wavelength is often set to the ultraviolet region for analysis. However, some components may be altered (destroyed) by ultraviolet rays. If the target component is significantly destroyed by ultraviolet rays, it is necessary to avoid using strong ultraviolet rays, and measure in the wavelength region other than the ultraviolet region such as the visible region and the infrared region, or use a neutral density filter to reduce the ultraviolet intensity. Must be lowered.

Therefore, conventionally, a time program function (Patent Document 1) that switches the measurement wavelength by designating time is provided, and measurement is performed at a wavelength at which the target component does not change within the peak time range of the target component of the chromatogram. In this time range, there existed detectors that have a function of switching the measurement wavelength, for example, by measuring at a wavelength in the ultraviolet region.

However, the current time program function only has a command to “specify the measurement wavelength”. For example, “only the target component peak avoids ultraviolet and the other component peaks are measured simultaneously in the sample absorption wavelength and ultraviolet region”. Setting was complicated when trying to set.

An object of the present invention is to solve these problems and to provide a chromatographic control device capable of measuring impurities and performing simultaneous analysis with simple settings and without altering target components.

The chromatograph control device according to the present invention, which has been made to solve the above problems,
a) a single wavelength measurement unit for operating the chromatograph in the single wavelength measurement mode;
b) a multi-wavelength measurement unit for operating the chromatograph in the multi-wavelength measurement mode;
c) A mode switching unit that switches between a single wavelength measurement mode and a multi-wavelength measurement mode according to the time range of the chromatogram.

In the chromatograph control device according to the present invention, as described above, the single wavelength measuring unit irradiates the measurement object with light of only one wavelength, and measures the light transmitted therethrough. The multi-wavelength measurement unit irradiates the measurement target with light having a plurality of wavelengths simultaneously (or substantially simultaneously), and measures the light transmitted through the measurement target.

The mode switching unit switches the operation of the single wavelength measurement unit (single wavelength measurement mode) and the operation of the multi wavelength measurement unit (multiwavelength measurement mode) according to the time range of the chromatogram. For example, in the time zone within the peak range of the target component of the chromatogram, the single wavelength measurement mode is used to measure at one wavelength so that the target component does not change, and the target component and other components are detected in other time zones. Measure in the multi-wavelength measurement mode.

* The time zone of the peak of the target component is examined in advance by measuring with the same sample.

In the chromatograph control device according to the present invention, the single wavelength measurement mode and the multi-wavelength measurement mode can be properly used in one chromatographic measurement (chromatogram), so that the target component can be simply not altered. In addition, it is possible to control a chromatograph capable of simultaneously detecting other component peaks.

1 is an overall configuration diagram of a liquid chromatograph that can be implemented by the present invention. The schematic block diagram of an example of the 1 wavelength detector of a liquid chromatograph. The schematic block diagram of an example (photodiode array type) of the multiwavelength detector of a liquid chromatograph. The schematic block diagram of the other example (light source switching type) of the multi-wavelength detector of a liquid chromatograph. The schematic block diagram of further another example (spectral element rotation type) of the multi-wavelength detector of a liquid chromatograph. The schematic block diagram of the control apparatus for liquid chromatographs which is one Example of this invention. The figure which shows an example of the time program creation screen displayed on the screen of the workstation connected to the control apparatus for liquid chromatographs of an Example. The front view of the operation panel containing the input part and display part of the control apparatus for liquid chromatographs of an Example. The figure which shows the example of 1 display of the display part at the time of creating the time program in the control apparatus for liquid chromatographs of an Example. The figure which shows another example of a display of the display part at the time of creating the time program in the control apparatus for liquid chromatographs of an Example.

An example of measurement by a liquid chromatograph using the chromatograph control device (hereinafter referred to as “control device”) according to the present invention will be described. The overall configuration of the liquid chromatograph 10 of the present embodiment is as shown in FIG. 1 and includes a sorting function (sorting unit 16). The detector 15 is of the type shown in FIG. 3C, and the spectroscopic element 22 is provided with a rotation drive device 27 that changes its angle in order to change the spectroscopic wavelength. As the light source, either a D2 (deuterium) lamp or a W (tungsten) lamp can be selected and used.

The chromatographic system 100 for controlling the liquid chromatograph 10 is configured to perform a series of operations of separating each component contained in the sample by controlling each part of the liquid chromatograph 10 and further separating the target component. In addition to the

control units

33, 34, 35, and 36 that control the pump 13, the injector 14, the detector 15, and the sorting unit 16, the system controller 30 and the workstation 40 are included. Each of the

control units

33, 34, 35, 36 and the system controller 30 includes a computer and a dedicated control program. The workstation 40 is a general-purpose computer in which various dedicated and general-purpose programs are installed, and can control almost all operations of the liquid chromatograph 10 through the system controller 30. Therefore, in this embodiment, the entire chromatographic system 100 corresponds to the chromatographic control device of the present invention.

In the workstation 40 of this embodiment, in addition to the central processing unit 31 and the storage unit 32 included in a general computer, a TM program creation unit 37 related to the present invention that assists the user in creating a time program, A TM program execution unit 38 for operating each part of the liquid chromatograph 10 according to the created time program is included. These will be described in detail later.

The storage unit 32 includes a temporary storage area used when the central processing unit 31 performs processing, and a non-volatile storage area that retains stored contents even when the power is turned off. The non-volatile storage area includes the dedicated control described above. In addition to the program, parameters for operating various parts of the liquid chromatograph are stored. This nonvolatile storage area also stores programs and parameters for operating the liquid chromatograph 10 in the 1 wavelength mode (single wavelength operation mode) and programs and parameters for operating in the 2 wavelength mode (multiwavelength operation mode). Has been.

The operation when the components in the sample are separated by the chromatographic system 100 of the present embodiment and one or more specific target components are collected will be described. If this sample contains components other than the target component (impurities, etc.), even if the absorbance measurement is performed with only one wavelength in the detector 15, how much of these components are present and can be sufficiently separated from the target peak. There is a possibility that it cannot be confirmed. Even in this case, the purity is not guaranteed. Therefore, by performing absorbance measurement at two wavelengths, it is possible to more reliably separate and extract only the target component. However, since ultraviolet rays are high energy radiation, this target component may be altered by ultraviolet rays. In this case, irradiation of the wavelength must be avoided in the peak time zone (time zone for fractionation) of the target component of the chromatogram. Therefore, in the chromatographic system 100 of the present embodiment, by preparing a time program in advance, detection by one wavelength (one wavelength mode) and detection by two wavelengths (two wavelength mode) in an arbitrary time zone of the chromatogram. Can be used properly.

When creating a time program on the workstation 40, a time program editing screen as shown in FIG. 5 is displayed on the screen. The user obtains the peak time zone (holding time zone) of one or more target components from the chromatogram obtained for the same sample in advance, and based on that data, the time zone of the 1 wavelength mode and the 2 wavelength mode Enter the time zone in the time program. In the example of FIG. 5, a two-wavelength measurement mode in which the time is measured at two wavelengths of 250 nm and 500 nm between 0.00 [min] and 8.20 [min], and the measurement is performed at only 500 nm between 8.20 [min] and 9.80 [min]. The one-wavelength measurement mode, 9.80 [min] and after, is set to the two-wavelength measurement mode that measures again at two wavelengths of 250 nm and 500 nm. The two wavelengths here may be different from the two wavelengths used in the time period from time 0.00 [min] to 8.20 [min].

Next, the sample is injected again from the injector 14 and the target component is separated. At this time, if the user designates execution of the previously created time program, the TM program execution unit 38 of the workstation 40 reads the time program from the storage unit 32 and performs an operation in accordance with the processing instruction of each row ( Instruct each control unit). That is, between the time 0.00 [min] and 8.20 [min], the spectral element 22 of the detector 15 is reciprocated in a short time to measure at two wavelengths (500 nm and 250 nm) described in the numerical value column. During the period from 8.20 [min] to 9.80 [min], the spectroscopic element 22 is held at a predetermined angle to perform measurement at one wavelength (500 nm) described in the numerical value column. After 9.80 [min], measure again at the specified two wavelengths.

Thus, the operation of the TM program execution unit 38 of the workstation 40 is executed by switching between the 1-wavelength mode and the 2-wavelength mode, and after confirming that the target component is not denatured and separated from the impurities, Are sorted by the sorting unit 16.

In the above embodiment, the detector 15 has been described with respect to the spectral element rotation type as shown in FIG. 3C. However, the present invention can be implemented even if the detector is a light source switching type as shown in FIG. 3B. be able to.

Although the case where the time program is edited by the workstation 40 has been described in the above embodiment, each line of the time program displayed on the display unit 42 by operating the input unit 41 of the system controller 30 or the detector control unit 35 is described. Data may be entered in the input field (FIGS. 7A and 7B).

In the above example, the target peak was measured at one wavelength and was measured at two wavelengths in a time range other than the target peak, but the target peak was measured at two wavelengths and measured at three wavelengths in the time range other than the target peak. Also good. That is, the number of wavelengths scheduled by the time program is not limited to one or two wavelengths.

DESCRIPTION OF SYMBOLS 10 ... Liquid chromatograph 11 ... Separation column 12 ... Mobile phase 13 ... Liquid feed pump 14 ... Injector 15 ... Detector 16 ... Sorting part 21 ... Light source 22 ... Spectral element 23 ... Splitting optical system 24 ... Sample cell 25 ... Light receiving part 27 ... Spectral element rotation drive device 30 ... System controller 31 ... Central processing unit 32 ... Storage unit 37 ... Time (TM) program creation unit 38 ... Time (TM) program execution unit 40 ... Chromatograph control workstation 41 ... Input unit 42 ... Display unit 100 ... Chromatograph system

Claims

a) a single wavelength measurement unit for operating the chromatograph in the single wavelength measurement mode;
b) a multi-wavelength measurement unit for operating the chromatograph in the multi-wavelength measurement mode;
c) A chromatographic control device comprising: a mode switching unit that switches between a single wavelength measurement mode and a multiwavelength measurement mode according to the time range of the chromatogram.
The chromatogram according to claim 1, further comprising a time program creation unit that allows a user to create a time program that is a schedule for switching between a single wavelength measurement mode and a multiwavelength measurement mode according to a time range of the chromatogram. Graph control device.
A) a computer for controlling the chromatograph; a) a single wavelength measurement unit for operating the chromatograph in the single wavelength measurement mode;
b) a multi-wavelength measurement unit for operating the chromatograph in the multi-wavelength measurement mode;
c) A chromatograph control program that functions as a mode switching unit that switches between a single wavelength measurement mode and a multiwavelength measurement mode according to the time range of the chromatogram.
Furthermore, it functions also as a time program creation part which makes a user create the time program which is the schedule of switching of the single wavelength measurement mode and multiwavelength measurement mode according to the time range of a chromatogram. Program for chromatographic control.