JP7120335B2 - Liquid chromatograph and analysis method using liquid chromatograph - Google Patents

Description

The present invention relates to a liquid chromatograph for analyzing a sample and an analysis method using the liquid chromatograph.

An elution method called gradient elution is known in the field of liquid chromatography. Gradient elution is a method of eluting a sample while continuously changing the composition (mixing ratio) of the mobile phase. High-pressure gradient systems and low-pressure gradient systems are known as liquid delivery systems for gradient elution.

For example, Patent Literature 1 describes two flow path configurations provided in a liquid chromatograph analyzer. The two channel configurations correspond respectively to a high pressure gradient system and a low pressure gradient system.

A high pressure gradient system comprises, for example, two solvent bottles and two pumps. Two mobile phases are respectively stored in the two solvent bottles. Two pumps each aspirate two mobile phases from two solvent bottles. A mixed mobile phase having an arbitrary mixing ratio is generated by mixing the two sucked mobile phases. At this time, the mixed mobile phase is generated by controlling the flow rate of each pump so that the flow rate ratio of each pump becomes the mixing ratio of the mixed mobile phase. This mixing method is called a high-pressure mixing method. Under the condition that the total flow rate of the mixed mobile phase is constant, the mixing ratio of the mixed mobile phase flowing downstream of each pump changes with time by controlling the flow rate ratio of each pump with time. Thereby, the composition (mixing ratio) of the mixed mobile phase used for analysis changes continuously. This time control of the mixing ratio of the mixed mobile phase is called a high-pressure gradient method (Fig. 2(a) of Patent Document 1).

A low-pressure gradient system comprises, for example, 3 solvent bottles, 3 valves and 1 pump. One pump is connected to each of the three solvent bottles via three valves. A single pump draws the mobile phase stored in the solvent bottle from the solvent bottle connected to the plurality of open valves. A mixed mobile phase having an arbitrary mixing ratio is generated by mixing a plurality of mobile phases sucked by one pump. At this time, the mixed mobile phase is generated by repeating the control of sequentially opening the valves so that the opening time ratio per unit time of each valve becomes the mixing ratio of the mixed mobile phase. This mixing method is called a low-pressure mixing method. Also, a valve configured to allow such control is called a low-pressure mixing valve. Under the condition that the total flow rate of the mixed mobile phase is constant, the mixing ratio of the mixed mobile phase flowing downstream of the three valves is temporally controlled by controlling the opening time ratio per unit time of each valve. Change. Thereby, the composition (mixing ratio) of the mixed mobile phase used for analysis changes continuously. This time control of the mixing ratio of the mixed mobile phase is called a low-pressure gradient method (Fig. 2(b) of Patent Document 1).
Patent No. 4525400 Japanese Patent Application Laid-Open No. 2004-138413 Patent No. 4228502

In the gradient system of the liquid chromatograph, the mixed mobile phase used for the analysis is set in advance before starting the analysis of the sample. At the start of sample analysis, if a mixed mobile phase with a different composition (mixing ratio) from the mixed mobile phase set as the conditions at the start of analysis exists in each channel of the liquid chromatograph, high-precision analysis can be performed immediately after the start of analysis. cannot be done.

Therefore, before the start of sample analysis, each of the plurality of channels in the liquid chromatograph must contain the mobile phase or mixed mobile phase that should be present in the channel at the start of sample analysis (mobile phase or mixed mobile phase to be used) mixed mobile phase). Patent Document 1 describes automatic purging of a specific channel in a liquid chromatograph with a mixed mobile phase to be used at the start of analysis. Further, Patent Document 1 describes that the mobile phase stored in the solvent bottle is sequentially and automatically purged into the channel connected to the solvent bottle in the two channel configurations described above.

In the above-described channel configuration corresponding to the high-pressure gradient system, the mobile phase in each solution bottle can be purged by, for example, sequentially controlling a plurality of pumps one by one so as to be in a liquid feeding state before the start of sample analysis. done. On the other hand, in the above channel configuration corresponding to the low-pressure gradient system, before the sample analysis is started, for example, while one pump is in operation, a plurality of valves located upstream of the pump are opened one by one. The mobile phase is purged from each solvent bottle by sequentially controlling the

In recent years, a liquid chromatograph has been developed that includes a low-pressure mixing valve and a high-pressure gradient system arranged in this order from upstream to downstream (see, for example, Patent Document 2). According to this liquid chromatograph, many types of mobile phases can be mixed at a desired mixing ratio, so it is possible to easily produce a wider variety of mobile phases. In such a liquid chromatograph as well, it is desirable to perform appropriate purging in order to analyze samples with high accuracy.

The object of the present invention is a liquid chromatograph that can easily generate various mobile phases for analysis and can analyze samples with high accuracy while changing the components of the mobile phase for analysis. An object of the present invention is to provide an analytical method using a liquid chromatograph.

(1) A liquid chromatograph according to one aspect of the present invention is a liquid chromatograph that analyzes a sample, comprising a plurality of flow paths respectively corresponding to a plurality of mobile phase source groups, and a plurality of channels included in each mobile phase source group A supply device that supplies one or more mobile phases from the mobile phase source as an intermediate mixed mobile phase to the flow channel corresponding to the mobile phase source group, and mixes the plurality of intermediate mixed mobile phases flowing in each of the plurality of flow channels , a mixer that generates a plurality of mixed intermediate mixed mobile phases as mobile phases for analysis, and a mixing ratio of the plurality of intermediate mixed mobile phases in the mobile phase for analysis is adjusted to a preset initial ratio at the start of sample analysis an analysis control unit that controls at least one of the supply device and the mixer so that the mixing ratio of the plurality of intermediate mixed mobile phases changes with time from the initial ratio during the analysis period of the sample; and a purge control unit that controls at least one of the supply device and the mixer so that the mixing ratio of the plurality of intermediate mixed mobile phases is adjusted to the initial ratio before the analysis of the initial ratio. When the term corresponding to any one of the plurality of intermediate mixed mobile phases in is set within a predetermined range including 0, the mixing ratio of the plurality of intermediate mixed mobile phases is adjusted to the initial ratio of control At least one of the feeder and the mixer is controlled such that a plurality of intermediate mixed mobile phases respectively flow through the plurality of channels.

In the liquid chromatograph, during the sample analysis period, one or more mobile phases are supplied from each mobile phase source group as an intermediate mixed mobile phase to the channel corresponding to the mobile phase source group. A plurality of intermediate mixed mobile phases flowing through a plurality of channels are mixed to generate an analytical mobile phase. This makes it possible to easily generate various mobile phases for analysis.

At the start of sample analysis, the mixing ratio of the plurality of intermediate mixed mobile phases in the mobile phase for analysis is adjusted to a preset initial ratio. Also, during the sample analysis period, the mixing ratio of the plurality of intermediate mixed mobile phases is adjusted such that the mixing ratio of the plurality of intermediate mixed mobile phases changes over time from the initial ratio.

An analysis mobile phase is generated such that the mixing ratio of a plurality of intermediate mixed mobile phases is adjusted to the initial ratio before starting sample analysis. In this case, at least one of the plurality of channels is purged using the intermediate mixed mobile phase to be used at the start of sample analysis.

Here, in the above purge operation, depending on the sample analysis conditions such as gradient elution, the flow rate of one of the plurality of intermediate mixed mobile phases flowing through the plurality of channels is set to 0 or nearly 0 at the start of sample analysis. may be This corresponds to the case where the term corresponding to one of the plurality of intermediate mixed mobile phases in the initial ratio is set within a predetermined range including zero. In this case, the flow path corresponding to the intermediate mixed mobile phase whose flow rate is set to zero or nearly zero cannot be purged only by the above purge operation.

Therefore, when any term in the initial ratio is set within a predetermined range including 0, the mixing ratio of a plurality of intermediate mixed mobile phases is adjusted to the initial ratio before the analysis of the sample is started. A plurality of intermediate mixed mobile phases are supplied to each of the plurality of channels prior to the purge operation. Thereby, a plurality of channels are purged with a plurality of intermediate mixed mobile phases, respectively. Analysis of the sample is then performed.

In this way, a plurality of channels are purged in advance with a plurality of intermediate mixed mobile phases before starting sample analysis. As a result, even if there is an intermediate mixed mobile phase that is not used at the start of the sample analysis and is used after the start of the analysis, a precisely generated analytical mobile phase with a preset mixing ratio can be used throughout the analysis period of the sample. can be used across Therefore, it becomes possible to analyze a sample with high accuracy while changing the components of the mobile phase for analysis.

(2) the purge control unit, when the term corresponding to one of the plurality of intermediate mixed mobile phases in the initial ratio is set within a predetermined range including 0, the plurality of At least one of the supply device and the mixer may be controlled so that the intermediate mixed mobile phases are sequentially supplied. In this case, multiple channels are individually purged with multiple mixed intermediate mobile phases.

(3) the purge control unit, when the term corresponding to one of the plurality of intermediate mixed mobile phases in the initial ratio is set within a predetermined range including 0, the plurality of At least one of the feeder and the mixer may be controlled so that the feeds of the intermediate mixed mobile phases are performed in parallel. In this case, multiple channels are purged in parallel with multiple mixed intermediate mobile phases.

(4) The liquid chromatograph further includes a setting unit that sets the initial ratio and sets the temporal change in the mixing ratio of the plurality of intermediate mixed mobile phases in the analysis mobile phase during the analysis period of the sample, and the analysis control The unit and the purge control unit may control at least one of the supply device and the mixer based on the temporal change in the mixing ratio set by the setting unit.

In this case, the mobile phase for analysis is appropriately and automatically generated based on the temporal change in the mixing ratio set during the sample analysis period, and an appropriate purge is automatically performed before starting the sample analysis. done. Therefore, the user does not have to perform complicated operations for purging.

(5) The purge control unit, before the analysis of the sample is started and before the intermediate mixed mobile phases are supplied to the plurality of flow paths, according to a predetermined order of the mobile phases, the plurality of At least one of a supply device and a mixer is controlled so that the mobile phase is sequentially supplied to the flow path corresponding to the mobile phase source group, and one or The mixing ratio of a plurality of mobile phases is set in advance, and the predetermined order of the mobile phases is a mobile phase that is not used for sample analysis, a mobile phase that is not used at the start of sample analysis, and a plurality of intermediate mixed mobile phases. and a mobile phase with a smaller mixing ratio term, and a mobile phase that is included in a plurality of intermediate mixed mobile phases and with a higher mixing ratio term.

As a result, before purging to respectively supply a plurality of intermediate mixed mobile phases to a plurality of channels, another Appropriate purging is performed for multiple flow paths.

(6) The supply device includes a plurality of pumps respectively corresponding to the plurality of mobile phase source groups and the plurality of flow paths, and each pump sucks and mixes the plurality of mobile phases from the corresponding mobile phase source group. Alternatively, a plurality of mixed mobile phases may be supplied to corresponding channels as an intermediate mixed mobile phase.

In this case, the pumps constitute a high-pressure gradient system. Therefore, by providing a low-pressure mixing valve on the upstream side of each pump, various gradient elutions are possible.

(7) A liquid chromatograph according to another aspect of the present invention is a liquid chromatograph for analyzing a sample, wherein each mobile phase source group includes a plurality of flow paths respectively corresponding to a plurality of mobile phase source groups Any of a supply device that supplies one or more mobile phases from a plurality of mobile phase sources as an intermediate mixed mobile phase to a channel corresponding to the mobile phase source group, and a plurality of intermediate mixed mobile phases that respectively flow in the plurality of channels A selector that selects as the mobile phase for analysis, and a preset one of a plurality of intermediate mixed mobile phases is selected as the mobile phase for analysis at the start of analysis of the sample and analyzed during the analysis period of the sample An analysis control unit that controls the selector so that another preset one of a plurality of intermediate mixed mobile phases is selected as the mobile phase for analysis, and a plurality of intermediate mixed mobile phases before the start of analysis of the sample. and a purge controller for controlling at least one of the supply device and the selector to flow through each of the plurality of flow paths.

In the liquid chromatograph, during the sample analysis period, one or more mobile phases are supplied from each mobile phase source group as an intermediate mixed mobile phase to the channel corresponding to the mobile phase source group. Any one of a plurality of intermediate mixed mobile phases flowing through a plurality of channels at the start of sample analysis is selected as the mobile phase for analysis. Another one of the plurality of intermediate mixed mobile phases is selected as the analytical mobile phase during the analysis of the sample. This makes it possible to easily generate various mobile phases for analysis.

A plurality of intermediate mixed mobile phases are supplied to the plurality of channels, respectively, before starting sample analysis. Thereby, a plurality of channels are purged with a plurality of intermediate mixed mobile phases, respectively. Analysis of the sample is then performed.

In this way, a plurality of channels are purged in advance with a plurality of intermediate mixed mobile phases before starting sample analysis. As a result, even if any of a plurality of intermediate mixed mobile phases is not used at the start of sample analysis and is used after the start of analysis, the analytical mobile phase accurately generated at the preset mixing ratio can be used for the sample. It can be used over the entire analysis period. Therefore, it becomes possible to analyze a sample with high accuracy while changing the components of the mobile phase for analysis.

(8) An analysis method using a liquid chromatograph according to still another aspect of the present invention is an analysis method using a liquid chromatograph for analyzing a sample, wherein the liquid chromatograph includes a plurality of mobile phase source groups It has a plurality of channels corresponding to each, and the analysis method is to use one or more mobile phases from a plurality of mobile phase sources included in each mobile phase source group as an intermediate mixed mobile phase during the analysis period of the sample. a step of supplying to channels corresponding to the source group; mixing a plurality of intermediate mixed mobile phases respectively flowing in the plurality of channels during the analysis period of the sample; A step of generating as a phase, and a plurality of intermediate mixtures during the analysis period of the sample so that the mixing ratio of the plurality of intermediate mixed mobile phases in the mobile phase for analysis is adjusted to a preset initial ratio at the start of sample analysis adjusting the mixing ratio of the plurality of intermediate mixed mobile phases so that the mixing ratio of the mobile phases changes over time from the initial ratio; generating a mobile phase for analysis such that the mixing ratio of the plurality of intermediate mixed mobile phases is adjusted to the initial ratio before starting analysis of the sample. The step of initializing the mixing ratio of the plurality of intermediate mixed mobile phases when the term corresponding to one of the plurality of intermediate mixed mobile phases in the initial ratio is set within a predetermined range including 0 A plurality of intermediate mixed mobile phases are provided to each of the plurality of channels prior to adjusting the ratio.

In the analysis method, one or a plurality of mobile phases are supplied from each mobile phase source group as an intermediate mixed mobile phase to the channel corresponding to the mobile phase source group during the sample analysis period. A plurality of intermediate mixed mobile phases flowing through a plurality of channels are mixed to generate an analytical mobile phase. This makes it possible to easily generate various mobile phases for analysis.

At the start of sample analysis, the mixing ratio of the plurality of intermediate mixed mobile phases in the mobile phase for analysis is adjusted to a preset initial ratio. Also, during the sample analysis period, the mixing ratio of the plurality of intermediate mixed mobile phases is adjusted such that the mixing ratio of the plurality of intermediate mixed mobile phases changes over time from the initial ratio.

An analysis mobile phase is generated such that the mixing ratio of a plurality of intermediate mixed mobile phases is adjusted to the initial ratio before starting sample analysis. In this case, at least one of the plurality of channels is purged using the intermediate mixed mobile phase to be used at the start of sample analysis.

If any term in the initial ratio is set within a predetermined range including 0, a purge operation to adjust the mixing ratio of the plurality of intermediate mixed mobile phases to the initial ratio before the analysis of the sample is started , a plurality of intermediate mixed mobile phases are supplied to the plurality of channels, respectively. Thereby, a plurality of channels are purged with a plurality of intermediate mixed mobile phases, respectively. Analysis of the sample is then performed.

In this way, a plurality of channels are purged in advance with a plurality of intermediate mixed mobile phases before starting sample analysis. As a result, even if there is an intermediate mixed mobile phase that is not used at the start of the sample analysis and is used after the start of the analysis, a precisely generated analytical mobile phase with a preset mixing ratio can be used throughout the analysis period of the sample. can be used across Therefore, it becomes possible to analyze a sample with high accuracy while changing the components of the mobile phase for analysis.

(9) when the term corresponding to one of the plurality of intermediate mixed mobile phases in the initial ratio is set within a predetermined range including 0, a plurality of intermediate mixed mobile phases before the start of sample analysis to each of the plurality of channels may comprise sequentially supplying a plurality of intermediate mixed mobile phases. In this case, multiple channels are individually purged with multiple mixed intermediate mobile phases.

(10) when the term corresponding to one of the plurality of intermediate mixed mobile phases in the initial ratio is set within a predetermined range including 0, a plurality of intermediate mixed mobile phases before the start of sample analysis to each of the plurality of channels may comprise supplying a plurality of intermediate mixed mobile phases in parallel. In this case, multiple channels are purged in parallel with multiple mixed intermediate mobile phases.

(11) The analysis method further includes a step of setting an initial ratio and setting a temporal change in the mixing ratio of the plurality of intermediate mixed mobile phases in the analysis mobile phase during the sample analysis period, Adjusting the mixing ratio of the plurality of intermediate mixed mobile phases in the mobile phase for analysis during and adjusting the mobile phase for analysis so that the mixing ratio of the plurality of intermediate mixed mobile phases is adjusted to the initial ratio before starting the analysis of the sample The step of generating may include adjusting the mixing ratio of the plurality of intermediate mixed mobile phases flowing through the plurality of channels based on the initial ratio set by the setting step and the temporal change in the mixing ratio.

In this case, the mobile phase for analysis is appropriately generated based on the temporal change in the mixing ratio set during the sample analysis period, and the appropriate purging is performed before starting the sample analysis.

(12) The analysis method includes a step of setting a mixing ratio of one or more mobile phases in a plurality of intermediate mixed mobile phases to be respectively flowed in a plurality of channels; Before the plurality of intermediate mixed mobile phases are supplied, the step of sequentially supplying the plurality of mobile phases of each mobile phase source group to the flow path corresponding to the mobile phase source group according to a predetermined order of the mobile phases. The predetermined order of mobile phases includes mobile phases that are not used for sample analysis, mobile phases that are not used at the start of sample analysis, and are included in a plurality of intermediate mixed mobile phases and have smaller mixing ratio terms. The order may be a mobile phase, and a mobile phase that is included in a plurality of intermediate mixed mobile phases and has a higher mixing ratio term.

As a result, before purging to respectively supply a plurality of intermediate mixed mobile phases to a plurality of channels, another Appropriate purging is performed for multiple flow paths.

(13) An analysis method using a liquid chromatograph according to still another aspect of the present invention is an analysis method using a liquid chromatograph for analyzing a sample, wherein the liquid chromatograph includes a plurality of mobile phase source groups It has a plurality of channels corresponding to each, and the analysis method is to use one or more mobile phases from a plurality of mobile phase sources included in each mobile phase source group as an intermediate mixed mobile phase during the analysis period of the sample. a step of supplying to a channel corresponding to a source group; a step of selecting, as a mobile phase for analysis, a preset one of a plurality of intermediate mixed mobile phases flowing through the plurality of channels at the start of sample analysis; During the analysis period of the sample, selecting another one preset from among the plurality of intermediate mixed mobile phases as the mobile phase for analysis; and respectively feeding the channels.

In the analysis method, one or a plurality of mobile phases are supplied from each mobile phase source group as an intermediate mixed mobile phase to the channel corresponding to the mobile phase source group during the sample analysis period. Any one of a plurality of intermediate mixed mobile phases flowing through a plurality of channels at the start of sample analysis is selected as the mobile phase for analysis. Another one of the plurality of intermediate mixed mobile phases is selected as the analytical mobile phase during the analysis of the sample. This makes it possible to easily generate various mobile phases for analysis.

A plurality of intermediate mixed mobile phases are supplied to the plurality of channels, respectively, before starting sample analysis. Thereby, a plurality of channels are purged with a plurality of intermediate mixed mobile phases, respectively. Analysis of the sample is then performed.

In this way, a plurality of channels are purged in advance with a plurality of intermediate mixed mobile phases before starting sample analysis. As a result, even if any of a plurality of intermediate mixed mobile phases is not used at the start of sample analysis and is used after the start of analysis, the analytical mobile phase accurately generated at the preset mixing ratio can be used for the sample. It can be used over the entire analysis period. Therefore, it becomes possible to analyze a sample with high accuracy while changing the components of the mobile phase for analysis.

ADVANTAGE OF THE INVENTION According to this invention, it becomes possible to generate various mobile phases for analysis easily, and to analyze a sample with high precision, changing the component of the mobile phase for analysis.

FIG. 1 is a diagram showing the configuration of a liquid chromatograph according to one embodiment of the present invention. FIG. 2 is a diagram for explaining an example of purging corresponding to the mobile phase for analysis generated in the first generation example. FIG. 3 is a diagram for explaining an example of purging corresponding to the mobile phase for analysis generated in the first generation example. FIG. 4 is a diagram for explaining the problem that proper purging is not performed. FIG. 5 is a diagram for explaining an example of purging corresponding to the mobile phase for analysis generated in the second generation example. FIG. 6 is a diagram for explaining an example in which the two controls in FIG. 5 are performed in parallel. FIG. 7 is a diagram showing a configuration example of a liquid chromatograph according to another embodiment. FIG. 8 is a diagram showing another configuration example of a liquid chromatograph according to another embodiment. FIG. 9 is a diagram showing still another configuration example of a liquid chromatograph according to another embodiment.

[1] Configuration of liquid chromatograph FIG. 1 is a diagram showing the configuration of a liquid chromatograph according to one embodiment of the present invention. As shown in FIG. 1, the liquid chromatograph 100 according to the present embodiment includes a first adjustment unit 10, a second adjustment unit 20, an analytical mobile phase generation unit 30, a sample introduction unit 40, a column 50, detection It includes a device 60 , a control device 70 , an operation section 81 and a display section 82 .

The first adjustment section 10 and the second adjustment section 20 each include a first switching valve 11 and a second switching valve 21 . Each of the first and second switching valves 11 and 12 is a so-called low-pressure mixing valve. The low-pressure mixing valve has a plurality of inlet ports and one outlet port, and is configured to selectively open a plurality of flow paths between the plurality of inlet ports and one outlet port. In addition, the low-pressure mixing valve is configured to be able to discharge a plurality of liquids at an arbitrary ratio by adjusting the opening time between the plurality of flow paths per relatively minute unit time (for example, about 0.6 sec). be. The analytical mobile phase generator 30 has basically the same configuration as a so-called high-pressure gradient system, and includes a first pump 31 , a second pump 32 and a mixer 33 .

The first adjusting section 10 is provided with a plurality of (four in this example) bottles B1 to B4. Mobile phases of different types are stored in the bottles B1 to B4. The first switching valve 11 of the first adjustment unit 10 is connected to the bottles B1 to B4 by a plurality of (four in this example) pipes p1 to p4, respectively, and the analytical mobile phase generation unit 30 by a pipe p11. is connected to the inlet port of the first pump 31 of the . An outlet port of the first pump 31 is connected to the mixer 33 by a pipe p12.

The first switching valve 11 selectively allows the internal space of one of the pipes p1 to p4 to communicate with the internal space of the pipe p11. As a result, when the first pump 31 is in operation, the mobile phase stored in the bottle is sucked into the first pump 31 from any one of the bottles B1 to B4. Here, the state of the first switching valve 11 is such that, for example, two or more mobile phases stored in any two or more of the bottles B1 to B4 are switched to the first pump 31 at a predetermined rate per unit time. is switched in a time-sharing manner so that it is aspirated to In this case, in the first pump 31, two or more sucked mobile phases are mixed and supplied to the pipe P12 as a mixed mobile phase. The first pump 31 is configured to be able to change the amount of the mixed mobile phase supplied to the pipe P12 (flow rate: the amount of the mixed mobile phase flowing per unit time) based on the control of the controller 70, which will be described later. .

The second adjusting section 20 is provided with a plurality of (four in this example) bottles B5 to B8. Mobile phases of different types are stored in the bottles B5 to B8. The second switching valve 21 of the second adjustment unit 20 is connected to the bottles B5 to B8 by a plurality of (four in this example) pipes p5 to p8, respectively, and the analytical mobile phase generation unit 30 by a pipe p21. is connected to the inlet port of the second pump 32 of the . The outlet port of the second pump 32 is connected to the mixer 33 by a pipe p22.

The second switching valve 21 has the same configuration as the first switching valve 11, and selectively allows the internal space of one of the pipes p5 to p8 to communicate with the internal space of the pipe p21. Thereby, when the second pump 32 is in operation, the mobile phase stored in the one bottle is sucked into the second pump 32 from any one of the bottles B5 to B8. Here, the state of the second switching valve 21 is such that, for example, two or more mobile phases stored in any two or more of the bottles B5 to B8 are switched to the second pump 32 at a predetermined rate per unit time. is switched in a time-sharing manner so that it is aspirated to In this case, in the second pump 32, two or more sucked mobile phases are mixed and supplied to the pipe P22 as a mixed mobile phase. The second pump 32 is configured to be able to change the flow rate of the mixed mobile phase supplied to the pipe P22 under the control of the controller 70, which will be described later.

In the mixer 33, two types of mixed mobile phases supplied from the first pump 31 and the second pump 32 through the pipes p21 and p22 are basically mixed, and the mobile phase for analysis used for analysis is mixed. is generated. When only one of the first pump 31 and the second pump 32 operates, the mixed mobile phase supplied from the one pump passes through the mixer 33 as the mobile phase for analysis.

One end of a pipe p31 is connected to the mixer 33 . A sample introduction part 40, a column 50 and a detector 60 are provided in this order on the pipe p31. A mobile phase for analysis is supplied from the mixer 33 to the sample introduction section 40 through the pipe p31. The sample introduction unit 40 is, for example, an injector, and introduces a sample into the supplied mobile phase for analysis. The mobile phase for analysis into which the sample has been introduced is led to column 50 . In column 50, multiple components of the sample introduced into the analytical mobile phase are separated. Detector 60 detects each component of the sample separated by column 50 . The mobile phase for analysis that has passed through the detector 60 is sent to a drainage device (not shown) (see Patent Document 3).

An operation unit 81 is an input device such as a keyboard, mouse, or touch panel, and is connected to the control device 70 . The display unit 82 is a display device such as a liquid crystal display device, and is connected to the control device 70 .

The control device 70 is composed of, for example, a CPU and memory or a microcomputer. The control device 70 controls the first and second switching valves 11 and 12 as well as the first and second pumps 31 and 32, as indicated by the dashed-dotted arrows in FIG. The control device 70 also controls the sample introduction section 40 and the detector 60 . Further, the control device 70 causes the display unit 82 to display information for receiving input such as sample analysis conditions, and sets sample analysis conditions in response to the operation of the operation unit 81 by the user. . The sample analysis conditions include information for generating an analytical mobile phase used for sample analysis (hereinafter referred to as mobile phase generation information).

As shown in FIG. 1, the control device 70 includes an analysis control section 71, a purge control section 72 and a storage section 73 as functional sections. The storage unit 73 stores sample analysis conditions set by the user. Based on the analysis conditions stored in the storage unit 73, the analysis control unit 71 controls the first switching valve 11 and the second switching valve so that the mobile phase for analysis is generated according to the set mobile phase generation information. 21, controls the first pump 31 and the second pump 32;

The purge control unit 72 purges the pipes p11 and p12 on the upstream side of the mixer 33 with a mixed mobile phase having an appropriate composition (mixing ratio) based on the analysis conditions stored in the storage unit 73 before starting sample analysis. The first switching valve 11 and the first pump 31 are controlled so that In addition, the purge control unit 72, based on the analysis conditions stored in the storage unit 73, purges the pipes p21 and p22 on the upstream side of the mixer 33 with a mixed mobile phase having an appropriate composition (mixing ratio) before starting analysis of the sample. is purged, the second switching valve 21 and the second pump 32 are controlled. An example of control of the first switching valve 11, the second switching valve 21, the first pump 31, and the second pump 32 by the purge control unit 72 will be described later.

[2] Sample analysis by gradient elution Hereinafter, two or more of the four types of mobile phases stored in bottles B1 to B4 are transferred by controlling the first switching valve 11 while operating the first pump 31. A mixed mobile phase obtained by mixing phases at a preset first mixing ratio is called a first mixed mobile phase. Further, by controlling the second switching valve 21 while operating the second pump 32, two or more of the four types of mobile phases stored in the bottles B5 to B8 are switched to the preset second A mixed mobile phase obtained by mixing at a mixing ratio is called a second mixed mobile phase.

In the liquid chromatograph 100 according to the present embodiment, by simultaneously operating the first pump 31 and the second pump 32, the first and second mixed mobile phases are further mixed to form a new composition (mixed ratio) can be produced as an analytical mobile phase. At this time, by changing the operation of the first pump 31 and the second pump 32 over time, the mixing ratio of the first and second mixed mobile phases supplied to the pipes p12 and p22 is continuously changed. can be made Thereby, it is possible to analyze a sample by gradient elution with continuously changing composition of the analytical mobile phase.

In addition, in the present embodiment, the first mixing ratio for generating the first mixed mobile phase is fixed without changing with time during sample analysis. It is also assumed that the second mixing ratio for producing the second mixed mobile phase is also fixed without changing over time during the analysis of the sample.

(a) First Production Example of Mobile Phase for Analysis A first production example of the mobile phase for analysis used for gradient elution will be described. Hereinafter, the mobile phases stored in the bottles B1, B2, B5 and B6 in FIG. 1 are referred to as the first mobile phase, the second mobile phase, the third mobile phase and the fourth mobile phase, respectively. Further, in the following description, a preset mixing ratio of the first and second mixed mobile phases in the mobile phase for analysis corresponding to the start of sample analysis is referred to as a third mixing ratio. Further, a preset mixing ratio of the first and second mixed mobile phases in the mobile phase for analysis corresponding to the analysis of the sample is called a fourth mixing ratio.

It is assumed that the mobile phase generation information is set to use the first mixed mobile phase in which the first mobile phase and the second mobile phase are mixed at a first mixing ratio (60:40). . Also, it is assumed that the use of a second mixed mobile phase in which the third mobile phase and the fourth mobile phase are mixed at a second mixing ratio (80:20) is set. Furthermore, analysis so that the mixing ratio of the first mixed mobile phase and the second mixed mobile phase changes continuously from the third mixing ratio (90:10) to the fourth mixing ratio (10:90) It shall be set to generate the mobile phase for

In this case, the analysis control unit 71 sets the ratio of the flow rate of the first mixed mobile phase flowing into the mixer 33 to the flow rate of the second mixed mobile phase to the third mixing ratio (90:10) at the start of sample analysis. ), the first pump 31 and the second pump 32 are controlled. After that, the analysis control unit 71 controls the mixing ratio of the first and second mixed mobile phases from the third mixing ratio (90:10) to the fourth mixing ratio (10:10) from the start of the sample analysis to the end of the analysis. : 90), the first pump 31 and the second pump 32 are controlled so as to change continuously.

In addition, while the first pump 31 is operating, the analysis control unit 71 controls the first It controls the switching valve 11 . In addition, while the second pump 32 is operating, the analysis control unit 71 controls the second mobile phase so that the third mobile phase and the fourth mobile phase are mixed at the second mixing ratio (80:20). It controls the switching valve 21 .

(b) Second Production Example of Mobile Phase for Analysis A second production example of the mobile phase for analysis used for gradient elution will be described. In the second generation example, the mixing ratio of the first mixed mobile phase and the second mixed mobile phase is continuously from the third mixing ratio (100:0) to the fourth mixing ratio (0:100) It is assumed that the same mobile phase generation information as in the first generation example is set except that the mobile phase is generated so as to change to .

In this case, the analysis control unit 71 sets the ratio of the flow rate of the first mixed mobile phase flowing into the mixer 33 to the flow rate of the second mixed mobile phase to the third mixing ratio (100:0 ), the first pump 31 and the second pump 32 are controlled. At this start, the second pump 32 is stopped. After that, the analysis control unit 71 controls the mixing ratio of the first and second mixed mobile phases from the third mixing ratio (100:0) to the fourth mixing ratio (0 : 100).

As in the first generation example, the analysis control unit 71 sets the first mobile phase and the second mobile phase at the first mixing ratio (60:40) while the first pump 31 is operating. The first switching valve 11 is controlled so as to mix at . Further, as in the first generation example, while the second pump 32 is operating, the analysis control unit 71 sets the third mobile phase and the fourth mobile phase at the second mixing ratio (80:20). The second switching valve 21 is controlled so as to mix at .

[3] Purge Before the analysis of the sample is started, the mobile phase (hereinafter referred to as residual mobile phase ) and air bubbles are purged with a mobile phase of the composition (mixture ratio) used for the analysis.

Here, in the purge control unit 72, the term corresponding to either the first or second mixed mobile phase in the third mixing ratio set corresponding to the start of analysis of the sample is set to 0. Different control is performed depending on the case and other cases. The setting of the mobile phase generation information of the first generation example corresponds to the case where the terms of the first and second mixed mobile phases in the third mixing ratio are set to values other than zero. The fact that the mobile phase generation information of the second generation example is set means that one of the first and second mixed mobile phases in the third mixing ratio set corresponding to the start of analysis of the sample is set to zero.

(a) Purge corresponding to the first production example of the mobile phase for analysis As an example of control when the term corresponding to the first and second mixed mobile phases in the third mixing ratio is set to a value other than 0, A specific example of purge corresponding to the first generation example will be described.

2 and 3 are diagrams for explaining an example of purging corresponding to the mobile phase for analysis generated in the first generation example. In FIGS. 2 and 3, the flow of various mobile phases for purging is indicated by thick solid line, thick dashed line, thick dashed-dotted line, and thick dashed-double-dotted line.

As shown in FIG. 2 , the purge control unit 72 first controls the first pump 31 and the first switching valve 11 so that the mobile phase stored in the bottle B4 is supplied to the mixer 33 . This control is referred to as control C1. As a result, the mobile phase stored in the bottle B4 purges the existing residual mobile phase and air bubbles in the pipes p4, p11 and p12.

Next, the purge control section 72 controls the first pump 31 and the first switching valve 11 so that the mobile phase stored in the bottle B3 is supplied to the mixer 33 . This control is referred to as control C2. As a result, the existing residual mobile phase and air bubbles in the pipes p3, p11 and p12 are purged with the mobile phase stored in the bottle B3.

Next, the purge control unit 72 controls the first pump 31 and the first switching valve 11 so that the second mobile phase stored in the bottle B2 is supplied to the mixer 33. This control is referred to as control C3. As a result, the existing residual mobile phase and air bubbles in the pipes p2, p11 and p12 are purged with the second mobile phase stored in the bottle B2.

Next, the purge control section 72 controls the first pump 31 and the first switching valve 11 so that the first mobile phase stored in the bottle B1 is supplied to the mixer 33 . This control is referred to as control C4. As a result, the first mobile phase stored in the bottle B1 purges the existing residual mobile phase and air bubbles in the pipes p1, p11, and p12. In the above controls C1 to C4, the second pump 32 is kept stopped.

Next, the purge control unit 72 controls the second pump 32 and the second switching valve 21 so that the mobile phase stored in the bottle B8 is supplied to the mixer 33. This control is referred to as control C5. As a result, the mobile phase stored in the bottle B8 purges the existing residual mobile phase and air bubbles in the pipes p8, p21 and p22.

Next, the purge control section 72 controls the second pump 32 and the second switching valve 21 so that the mobile phase stored in the bottle B7 is supplied to the mixer 33 . This control is referred to as control C6. As a result, the mobile phase stored in the bottle B7 purges the existing residual mobile phase and air bubbles in the pipes p7, p21 and p22.

Next, as shown in FIG. 3, the purge control unit 72 operates the second pump 32 and the second switching valve 21 so that the fourth mobile phase stored in the bottle B6 is supplied to the mixer 33. Control. This control is referred to as control C7. As a result, the remaining mobile phase, air bubbles, etc. existing in the pipes p6, p21, p22 are purged with the fourth mobile phase stored in the bottle B6.

Next, the purge control unit 72 controls the second pump 32 and the second switching valve 21 so that the third mobile phase stored in the bottle B5 is supplied to the mixer 33. This control is referred to as control C8. As a result, the residual mobile phase, air bubbles, etc. existing in the pipes p5, p21, p22 are purged with the third mobile phase stored in the bottle B5.

Next, the purge control unit 72 controls the first switching valve 11, the second switching valve 21, the first pump 31, and the second pump 32 so as to operate under the same conditions as when the analysis of the sample is started. do. This control is referred to as control C9. Specifically, the purge control unit 72 controls the ratio between the flow rate of the first mixed mobile phase and the flow rate of the second mixed mobile phase flowing into the mixer 33 to be the third mixing ratio (90:10). Also, the first pump 31 and the second pump 32 are controlled. Also, the purge control unit 72 controls the first switching valve 11 so that the first mobile phase and the second mobile phase are mixed at the first mixing ratio (60:40). Furthermore, the purge control unit 72 controls the second switching valve 21 so that the third mobile phase and the fourth mobile phase are mixed at the second mixing ratio (80:20). This completes the purge corresponding to the first production example of the mobile phase for analysis.

In this example, the internal spaces of pipes p1, p2, p5 and p8 are purged with a first mobile phase, a second mobile phase, a third mobile phase and a fourth mobile phase, respectively. In addition, the internal spaces of the pipes p11 and p12 are purged with the first mixed mobile phase. Furthermore, the internal spaces of the pipes p21 and p22 are purged with the second mixed mobile phase. Furthermore, the internal space of the pipe p31 in FIG. 1 is purged with the analytical mobile phase in which the first mixed mobile phase and the second mixed mobile phase are mixed at a third mixing ratio (90:10). This makes it possible to supply a mobile phase having a predetermined component to the column 50 with high accuracy at the start of sample analysis.

Of the above controls C1 to C9, the controls C1 to C4 and the controls C5 to C8 may be performed in the reverse order. Further, among the above controls C1 to C9, the controls C1 to C4 and the controls C5 to C8 may be performed in parallel. Furthermore, the mobile phase used for purging by the controls C1, C2, C5, and C6 among the above controls C1 to C9 is not used for generating the mobile phase for analysis. Therefore, the controls C1, C2, C5, and C6 may be omitted under the condition that malfunction of the valve due to remaining air bubbles does not occur.

In the above controls C1 to C9, various mobile phases supplied to the mixer 33 are sent to the sample introduction section 40 through the pipe p31 in FIG. In the sample introduction section 40, the mobile phase and the mixed mobile phase supplied from the analysis mobile phase generation section 30 during purge control are discarded through a drain (not shown) (see Patent Document 3).

(b) Purge corresponding to second production example of mobile phase for analysis Control when the term corresponding to one of the first and second mixed mobile phases in the third mixing ratio is set to 0 As an example, a specific example of purge corresponding to the second generation example will be described.

When the mobile phase is produced in the second production example, proper purging is not performed in some of the pipes even if the above purge controls C1 to C9 are performed in sequence. This issue will be explained.

FIG. 4 is a diagram for explaining the problem that proper purging is not performed. As described above, in the second generation example of the mobile phase, at the start of sample analysis, the mixing ratio of the first and second mixed mobile phases flowing into the mixer 33 is the third mixing ratio (100:0). The first pump 31 and the second pump 32 are controlled so that In this case, when the purge control unit 72 sequentially performs the above controls C1 to C9, the second pump 32 is stopped in control C9. Therefore, the flow of the mobile phase and mixed mobile phase does not occur in the inner space of the pipes p5, p6, p21, and p22 in control C9. Therefore, only the third mobile phase purged by the control C8 remains in the internal spaces of the pipes p21 and p22 indicated by white arrows in FIG.

When sample analysis is started in this state, only the third mobile phase remaining in the pipes p21 and p22 flows into the mixer 33 immediately after the second pump 32 starts operating. Therefore, a mixture of the first mixed mobile phase and the third mobile phase is produced as the mobile phase for analysis. This analytical mobile phase does not contain the components of the fourth mobile phase. As a result, the analytical accuracy of the sample in the initial stage is reduced.

Therefore, when the term corresponding to one of the first and second mixed mobile phases in the third mixing ratio is set to 0, the purge control unit 72 causes the first mixed mobile phase to , p12 are purged. In addition, when the flow rate of the first or second mixed mobile phase flowing through one of the pipes p12 and p22 is set to 0 at the start of sample analysis, the purge control unit 72 is set to 0 with the second mixed mobile phase. Control is performed to purge the pipes p21 and p22.

FIG. 5 is a diagram for explaining an example of purging corresponding to the mobile phase for analysis generated in the second generation example. In FIG. 5, the flows of various mobile phases for purging are indicated by thick solid lines and thick dotted arrows.

In this example, the purge control unit 72 first sequentially performs the controls C1 to C8 shown in FIGS. After that, the purge control unit 72 controls the first pump 31 and the first switching valve 11 so that the first mixed mobile phase is supplied to the pipe p12. This control is referred to as control C11. As a result, the residual mobile phase, air bubbles, etc. existing in the pipes p11 and p12 are purged with the first mixed mobile phase.

Next, the purge control unit 72 controls the second pump 32 and the second switching valve 21 so that the second mixed mobile phase is supplied to the pipe p22. This control is referred to as control C12. As a result, the residual mobile phase, air bubbles, etc. existing in the pipes p21 and p22 are purged with the second mixed mobile phase. After that, the purge control unit 72 performs control C9 in FIG. That is, the purge control unit 72 controls the first switching valve 11, the second switching valve 21, the first pump 31, and the second pump 32 so as to operate under the same conditions as when the analysis of the sample is started. .

According to the above controls C11 and C12, the pipe p12 is purged with the first mixed mobile phase and the pipe p22 is purged with the second mixed mobile phase before starting the sample analysis. As a result, the analytical mobile phase having preset components can be used immediately after the start of sample analysis. Therefore, it is possible to prevent a decrease in sample analysis accuracy in the initial stage and to analyze the sample with high accuracy.

The above controls C11 and C12 may be performed in reverse order. Also, the above controls C11 and C12 may be performed in parallel. FIG. 6 is a diagram for explaining an example in which the two controls C11 and C12 in FIG. 5 are performed in parallel. In FIG. 6, the flow of various mobile phases for purging is indicated by either thick solid line, thick dotted line, thick dashed-dotted line, and thick two-dotted dashed line.

As shown in FIG. 6, in this example, after the controls C1 to C8 of FIGS. 2 and 3 are sequentially performed, the controls C11 and C12 of FIG. 5 are simultaneously performed before the control C9 is performed. This control is referred to as control C13. According to the control C13, the purging of the pipe p12 with the first mixed mobile phase and the purging of the pipe p22 with the second mixed mobile phase are performed in parallel.

In control C13, both the first pump 31 and the second pump 32 need only be operating. The mixing ratio of the first and second mixed mobile phases flowing into the mixer 33 by the first pump 31 and the second pump 32 by the control C13 is, for example, (50:50). In this case, the piping connected to the first pump 31 and the piping connected to the second pump 32 can be purged with the same efficiency. Note that the mixing ratio of the first and second mixed mobile phases flowing into the mixer 33 by the first pump 31 and the second pump 32 by the control C13 is not limited to (50:50). This mixing ratio may be set to a ratio other than (50:50) depending on the properties of the mobile phase used (viscosity, etc.), the properties of the first pump 31, the properties of the second pump 32, etc. .

In this example as well, the mobile phase used for purging by the controls C1, C2, C5, and C6 among the above controls C1 to C9 is not used for generating the mobile phase for analysis. Therefore, the controls C1, C2, C5 and C6 may be omitted. Furthermore, in this example, the operations of the controls C9 and C11 are the same. Therefore, the control C11 of the above controls C9 and C11 may be omitted. In this case, the time required for purging can be shortened.

[4] Effect (a) In the liquid chromatograph 100 according to the present embodiment, the first and second mobile phases mixed while being sucked are piped as the first mixed mobile phase during the sample analysis period. supplied to p12. At this time, the mixture ratio of the first and second mobile phases in the first mixed mobile phase is adjusted to a predetermined first mixture ratio. Also, the third and fourth mobile phases mixed while being sucked are supplied to the pipe p22 as the second mixed mobile phase. At this time, the mixture ratio of the third and fourth mobile phases in the second mixed mobile phase is adjusted to a predetermined second mixture ratio. Furthermore, during the sample analysis period, the mixing ratio of the first and second mixed mobile phases flowing through the pipes p21 and p22 is adjusted to a preset mixing ratio to generate the mobile phase for analysis. This makes it possible to easily generate various mobile phases for analysis.

The flow rates of the first and second mixed mobile phases flowing through the pipes p21 and p22 are adjusted to be the product of the total flow rate and the mixing ratio. The total flow rate is the amount of mobile phase (analytical mobile phase) flowing downstream of the mixer 33 per unit time. Gradient elution is performed by temporally changing the mixing ratio of the first and second mixed mobile phases in the analytical mobile phase generated during the analysis period from the third mixing ratio to the fourth mixing ratio.

When the term corresponding to one of the first and second mixed mobile phases in the third mixing ratio set corresponding to the start of sample analysis is set to 0, before the start of sample analysis At the same time, the first mixed mobile phase is supplied to pipe p12 and the second mixed mobile phase is supplied to pipe p22. As a result, the pipes p12 and p22 are purged with the first and second mixed mobile phases, respectively. After that, the first or second mixed mobile phase is supplied to either one of the pipes p12 and p22 at the third mixing ratio set at the start of sample analysis. As a result, one of the pipes p12 and p22 is purged with the first or second mixed mobile phase. Analysis of the sample is then performed.

On the other hand, when the term corresponding to the first and second mixed mobile phases in the third mixing ratio set corresponding to the start of sample analysis is set to other than 0, before the start of sample analysis , the first and second mixed mobile phases are supplied to the pipes p12 and p22 at the third mixing ratio set at the start of sample analysis. As a result, the pipes p12 and p22 are purged with the first and second mixed mobile phases, respectively. Analysis of the sample is then performed.

In these cases, since the pipes p12 and p22 are purged in advance with the first and second mixed mobile phases before the start of sample analysis, the analysis is started with an analytical mobile phase that has been accurately generated at a preset mixing ratio. It can be used immediately after. Therefore, gradient elution can be performed with high precision. As a result, it becomes possible to analyze the sample with high accuracy.

(b) In addition, in the liquid chromatograph 100 described above, the temporal change in the mixing ratio of the first mixed mobile phase and the second mixed mobile phase mixed in the mixer 33 is set as the mobile phase generation information. is possible. The analysis control unit 71 generates the mobile phase for analysis based on the set mobile phase generation information. Thereby, the generation of the set analysis mobile phase is performed appropriately and automatically. In addition, the purge control unit 72 performs various purges based on the set mobile phase generation information. Appropriate purging is thereby automatically performed based on the temporal change in the set mixing ratio. Therefore, the user does not need to perform complicated operations for generating and purging the mobile phase for analysis.

(c) In the purging examples of FIGS. 2 and 3, a plurality of mobile phases stored in a plurality of bottles B1 to B8 are purged in advance before the first and second mixed mobile phases are purged. are carried out sequentially according to the order of the mobile phases given.

Here, the predetermined order of the mobile phases includes the mobile phase not used for sample analysis, the mobile phase not used at the start of sample analysis, the first or second mixed mobile phase and the mixing ratio Mobile phases with smaller terms and mobile phases that are included in the first or second mixed mobile phase and have higher mixing ratio terms.

As a result, before the pipes p12 and p22 are purged with the first and second mixed mobile phases, the multiple pipes p1 to p8 connected to the multiple bottles B1 to B8 are properly purged.

[5] Other Embodiments (a) In the above embodiment, the first and second mixed mobile phases are each set to The necessity of purging supplied to the pipes p12 and p22 is determined, but the present invention is not limited to this.

Even if all terms in the third mixing ratio are not zero, if any term has a value close to zero, the first and Purging with a second mixed mobile phase may not be possible. Thus, if either term is set within a predetermined range that includes 0 (eg, 0 to 5), then the first and second mixtures before purging according to the third mixture ratio Purging may be performed by supplying the mobile phase to the pipes p12 and p22, respectively.

The above range is determined by considering the characteristics of the mobile phase used, the length of the pipe, the characteristics of the pump, etc., and the residual mobile phase and air bubbles in the target pipe are sufficiently removed by purging according to the third mixing ratio. It is desirable to be set within a range that is considered to be unremovable.

(b) The analytical mobile phase generator 30 according to the above embodiment has a configuration of a high-pressure gradient system including two pumps and a low-pressure mixing valve connected to the inlet port of each pump. It is not limited to this. The analytical mobile phase generator 30 may have a high-pressure gradient system configuration in which three or more pumps are included and a low-pressure mixing valve is connected to the inlet port of each pump, instead of the configuration described above.

In this case, each of the third and fourth mixing ratios is a mixing ratio of three or more mixed mobile phases instead of a mixing ratio of two mixed mobile phases. By setting the third and fourth mixing ratios for three or more mixed mobile phases, more mixed mobile phases can be mixed at a desired mixing ratio. Therefore, more diverse gradient elution is possible.

Even in this case, when the term corresponding to any one of the three or more mixed mobile phases in the third mixing ratio is set to 0 or within a predetermined range including 0, the above embodiment Purge control similar to the controls C11 to C13 in . Thereby, it becomes possible to analyze a sample with high accuracy while changing the components of the mobile phase for analysis.

(c) The analytical mobile phase generator 30 may have a configuration of a low-pressure gradient system with one pump instead of a configuration of a high-pressure gradient system with two or more pumps. Specifically, the analytical mobile phase generator 30 may have a configuration including a low-pressure mixing valve and one pump.

FIG. 7 is a diagram showing a configuration example of a liquid chromatograph according to another embodiment. The liquid chromatograph 100 in FIG. 7 differs from the liquid chromatograph 100 in FIG. 1 in the configuration of the analytical mobile phase generator 30 .

The analytical mobile phase generator 30 of FIG. 7 includes a third pump 36 , a switching valve 37 and a mixer 33 . The switching valve 37 is a low pressure mixing valve that includes two inlet ports and one outlet port. One inlet port of the switching valve 37 is connected to the first switching valve 11 via a pipe p12. The other inlet port of the switching valve 37 is connected to the second switching valve 21 via a pipe p22. A pipe p31 is connected to the outlet port of the switching valve 37 . The pipe p31 is provided with a third pump 36 and a mixer 33 in this order from upstream to downstream. In this configuration, by controlling the switching valve 37 when the third pump 36 is in operation, the channel open time between the pipes p12 and p31 per unit time and the channel open time between the pipes p12 and p31 The ratio is adjusted. Thereby, the first mixed mobile phase and the second mixed mobile phase can be mixed at a desired mixing ratio.

Also in this case, as in the above embodiment, the components of the mobile phase for analysis are changed by performing purge control based on the terms of the first and second mixed mobile phases at the third mixing ratio. It becomes possible to analyze the sample with high accuracy while maintaining the accuracy.

In the liquid chromatograph 100 of FIG. 7, the first and second mixed mobile phases supplied from the switching valve 37 to the third pump 36 per unit time are mixed in the third pump 36. If present, the mixer 33 may not be provided.

(d) The analytical mobile phase generator 30 may have a configuration including one pump and a select valve instead of the configuration of a high-pressure gradient system having two or more pumps. Here, the select valve is configured to be capable of selectively opening a plurality of flow paths between a plurality of inlet ports and one outlet port. It is different from the low-pressure mixing valve in that it cannot be performed at high speed (micro cycle).

FIG. 8 is a diagram showing another configuration example of a liquid chromatograph according to another embodiment. The liquid chromatograph 100 in FIG. 8 differs from the liquid chromatograph 100 in FIG. 1 in the configuration of the analytical mobile phase generator 30 .

The analytical mobile phase generator 30 of FIG. 8 includes a fourth pump 38 and a select valve 39 . Select valve 39 includes two inlet ports and one outlet port. One inlet port of the select valve 39 is connected to the first switching valve 11 via a pipe p12. The other inlet port of the select valve 39 is connected to the second switching valve 21 via a pipe p22.

An outlet port of the select valve 39 is connected to one end of a pipe p31. A fourth pump 38 is attached between the select valve 39 and the sample introduction section 40 in the pipe p31. The select valve 39 is a selector that selects either the first mixed mobile phase flowing through the pipe p12 or the second mixed mobile phase flowing through the pipe p22 as the mobile phase for analysis when the fourth pump 38 operates. function as

In the liquid chromatograph 100 of FIG. 8, for example, one of the first and second mixed mobile phases flowing through the pipes p12 and p22 is selected by the select valve 39 as the mobile phase for analysis at the start of sample analysis. The other of the first and second mixed mobile phases is selected as the analytical mobile phase by the select valve 39 during the sample analysis period. This makes it possible to easily generate various mobile phases for analysis.

Here, in the liquid chromatograph 100 of FIG. 8, under the control of the purge control unit 72 of the control device 70, the first mixed mobile phase is supplied to the pipe p12 and the second mixed mobile phase is supplied to the pipe p12 before starting the analysis of the sample. A phase is supplied to line p22. As a result, the pipes p12 and p22 are purged with the first and second mixed mobile phases, respectively. Analysis of the sample is then performed.

In this manner, the pipes p12 and p22 are purged with the first and second mixed mobile phases in advance before starting sample analysis. Thereby, even if one of the first and second mixed mobile phases is not used at the start of sample analysis and is used after the start of analysis, the mobile phase for analysis is accurately generated at a preset mixing ratio can be used throughout the analysis period of the sample. Therefore, as in the above embodiment, it becomes possible to analyze a sample with high accuracy while changing the components of the mobile phase for analysis.

In the example of FIG. 8, the select valve 39 of the analysis mobile phase generator 30 may have three or more inlet ports, and the three or more inlet ports are further connected to low-pressure mixing valves. good too. Also in this case, before the analysis of the sample is started, the pipes connected to three or more inlet ports of the select valve 39 are purged with the mixed mobile phase generated at a preset mixing ratio. Thereby, it becomes possible to analyze a sample with high accuracy while changing the components of the mobile phase for analysis.

(e) In the above embodiment, the first and second switching valves 11 and 12 are low-pressure mixing valves, but the present invention is not limited to this. The first adjustment section 10 may include a select valve instead of the first switching valve 11 . Also, the second adjustment unit 20 may include a select valve instead of the second switching valve 12 .

FIG. 9 is a diagram showing still another configuration example of a liquid chromatograph according to another embodiment. The liquid chromatograph 100 in FIG. 9 differs from the liquid chromatograph 100 in FIG. 1 in the configuration of the first and second adjustment units 10 and 20.

The first adjustment section 10 in FIG. 9 includes a select valve 11x. Select valve 11x includes three inlet ports and one outlet port. Three inlet ports of the select valve 11x are connected to bottles B1, B2 and B3 via pipes p1, p2 and p3, respectively. An outlet port of the select valve 11x is connected to an inlet port of the first pump 31 via a pipe p11.

The second adjustment section 20 in FIG. 9 includes a select valve 21x. Select valve 21x includes three inlet ports and one outlet port. Three inlet ports of the select valve 21x are connected to bottles B5, B6 and B7 via pipes p5, p6 and p7, respectively. The outlet port of the select valve 21x is connected to the inlet port of the second pump 32 via a pipe p21.

In this configuration, the first adjustment unit 10 selects one of the plurality of mobile phases stored in the bottles B1, B2, and B3 as the first mixed mobile phase from the outlet port. let it flow. In addition, the second adjustment unit 20 selectively causes one of the plurality of mobile phases stored in the bottles B5, B6, and B7 to flow out from the outlet port as the second mixed mobile phase.

Also in this case, as in the above embodiment, the components of the mobile phase for analysis are changed by performing purge control based on the terms of the first and second mixed mobile phases at the third mixing ratio. It becomes possible to analyze the sample with high accuracy while maintaining the accuracy.

Each of the select valves 11x and 21X is configured to include three inlet ports and one outlet port, but may be configured to include two inlet ports and one outlet port. It may be configured to include four inlet ports and one outlet port. In this case, the select valves 11x and 21x can be connected to as many bottles as the number of inlet ports.

Further, in the example of FIG. 9, the first and second adjustment units 10 each include select valves 11x and 21x, but one of the first and second adjustment units 10 includes the select valve and the first and second adjustment units 10 include the select valves. The other of the two adjustment units 10 may include a low pressure mixing valve. That is, in the liquid chromatograph 100 of FIG. 9, only the first adjusting section 10 may be replaced with the first adjusting section 10 of FIG. Alternatively, in the liquid chromatograph 100 of FIG. 9, only the second adjusting section 20 may be replaced with the second adjusting section 20 of FIG. Furthermore, in the liquid chromatograph 100 of FIG. 9, only the analytical mobile phase generator 30 may be replaced with the analytical mobile phase generator 30 of FIG. 7 or FIG.

(f) In the above embodiments, a general high-performance liquid chromatograph was described as an example of a liquid chromatograph, but the present invention is not limited to this. The configuration including the above-described first adjustment unit 10, second adjustment unit 20, analytical mobile phase generation unit 30, and control device 70 is not limited to high-performance liquid chromatographs, and can be applied to supercritical fluid chromatographs. can be done. Also in this case, the same effect as in the above embodiment can be obtained. Therefore, liquid chromatographs according to the present invention include supercritical fluid chromatographs. A back pressure regulator is provided in the supercritical chromatograph so that the supercritical fluid does not vaporize. Therefore, in supercritical chromatography, it is necessary to purge at a relatively low flow rate compared to high performance liquid chromatography.

(g) The first adjustment unit 10 according to the above embodiment mixes a plurality of mobile phases stored in the bottles B1 to B4 by one first switching valve 11, which is a low-pressure mixing valve. The invention is not so limited. For example, the first adjustment unit 10 has a branch pipe having pipes p1, p2, p3, and p4 as branch pipes and a pipe p11 as a main pipe, and a plurality of pipes attached to pipes p1, p2, p3, and p4, respectively. It may have a valve. In this case, a function similar to that of the first switching valve 11 is realized by switching the open/close state of each valve.

In addition, the second adjustment unit 20 according to the above embodiment mixes a plurality of mobile phases stored in the bottles B5 to B8 by one second switching valve 21, which is a low-pressure mixing valve. is not limited to this. For example, the second adjustment unit 20 has a branch pipe with pipes p5, p6, p7, and p8 as branch pipes and a pipe p21 as a main pipe, and a plurality of pipes attached to pipes p5, p6, p7, and p8, respectively. It may have a valve. In this case, a function similar to that of the second switching valve 21 is realized by switching the open/close state of each valve.

(h) In the above embodiment, each of the first and second adjustment units 10 and 20 is configured to be able to use four bottles, but the present invention is not limited to this. Each of the first and second adjustment units 10 and 20 may be configured to be able to use five or more bottles, or may be configured to be able to use three or less bottles.

(i) In the liquid chromatograph 100 according to the above embodiment, a low-pressure mixing chamber for realizing the same function as the first and second adjustment units 10 and 20 is further downstream of the first adjustment unit 10 . A valve or select valve may be provided. Further, a low-pressure mixing valve or a select valve may be provided upstream of the second adjustment section 20 to achieve the same function as the first and second adjustment sections 10 and 20 . In this case, a further diversification of mobile phases that can be produced is realized.

[6] Correspondence between each constituent element of the claims and each part of the embodiment An example of correspondence between each constituent element of the claim and each part of the embodiment will be described below.

In the above embodiment, the bottles B1 to B8 are examples of a plurality of mobile phase sources, and the bottle group consisting of the bottles B1 to B4 and the bottle group consisting of the bottles B5 to B8 are examples of the mobile phase source group, Pipes p12 and p22 are examples of flow paths.

1, the combination of the first switching valve 11, the second switching valve 21, the first pump 31 and the second pump 32, the first switching valve 11, the second switching valve 21 and the The combination of the third pump 36, the combination of the first switching valve 11, the second switching valve 21 and the fourth pump 38 in FIG. A combination of two pumps 32 is an example of a feeder.

Further, the mixer 33 is an example of a mixer, the first and second mixed mobile phases are examples of an intermediate mixed mobile phase, the third mixing ratio is an example of an initial ratio, and the select valve 39 is a selector. is an example of

Various other elements having the structure or function described in the claims can be used as each component of the claims.

Claims (13)

A liquid chromatograph for analyzing a sample,
a plurality of channels respectively corresponding to a plurality of mobile phase source groups;
a supply device that supplies one or more mobile phases from a plurality of mobile phase sources included in each mobile phase source group as an intermediate mixed mobile phase to a channel corresponding to the mobile phase source group;
a mixer for mixing a plurality of intermediate mixed mobile phases respectively flowing in the plurality of channels and generating the mixed plurality of intermediate mixed mobile phases as mobile phases for analysis;
The plurality of intermediate mixed mobile phases are adjusted so that the mixing ratio of the plurality of intermediate mixed mobile phases in the mobile phase for analysis is adjusted to a preset initial ratio at the start of analysis of the sample and during the analysis period of the sample an analysis control unit that controls at least one of the supply device and the mixer such that the mixing ratio of the is temporally changed from the initial ratio;
a purge control unit that controls at least one of the supply device and the mixer so that the mixing ratio of the plurality of intermediate mixed mobile phases is adjusted to the initial ratio before starting analysis of the sample;
When the term corresponding to one of the plurality of intermediate mixed mobile phases in the initial ratio is set within a predetermined range including 0, the purge control unit performs the plurality of intermediate mixed mobile phases Prior to the control of adjusting the mixing ratio of the liquid chromatography to the initial ratio, at least one of the supply device and the mixer is controlled so that the plurality of intermediate mixed mobile phases flow through the plurality of channels, respectively. graph. When the term corresponding to one of the plurality of intermediate mixed mobile phases in the initial ratio is set within a predetermined range including 0, the purge control unit performs 2. The liquid chromatograph according to claim 1, wherein at least one of said supply device and said mixer is controlled such that said plurality of intermediate mixed mobile phases are sequentially supplied. When the term corresponding to one of the plurality of intermediate mixed mobile phases in the initial ratio is set within a predetermined range including 0, the purge control unit performs 2. The liquid chromatograph according to claim 1, wherein at least one of said supply device and said mixer is controlled so that said plurality of intermediate mixed mobile phases are supplied in parallel. A setting unit that sets the initial ratio and sets a temporal change in the mixing ratio of the plurality of intermediate mixed mobile phases in the mobile phase for analysis during the analysis period of the sample,
4. The analysis control unit and the purge control unit control at least one of the supply device and the mixer based on a temporal change in the mixing ratio set by the setting unit. 1. The liquid chromatograph according to item 1. The purge control unit, before starting the analysis of the sample and before supplying the plurality of intermediate mixed mobile phases to the plurality of channels, performs the plurality of purges of each mobile phase source group in accordance with a predetermined order of mobile phases. at least one of the supply device and the mixer so that the mobile phase is sequentially supplied to the flow path corresponding to the mobile phase source group,
mixing ratios of one or more mobile phases in a plurality of intermediate mixed mobile phases to be respectively flowed through the plurality of channels are set in advance,
The predetermined order of the mobile phases includes a mobile phase that is not used for analysis of the sample, a mobile phase that is not used at the start of analysis of the sample, and a plurality of intermediate mixed mobile phases, and the mixing ratio term is 4. The liquid chromatograph according to any one of claims 1 to 3, wherein the smaller mobile phase is included in the plurality of intermediate mixed mobile phases and the mixing ratio term is in descending order of the mobile phase. The supply device is
including a plurality of pumps respectively corresponding to the plurality of mobile phase source groups and the plurality of flow paths,
Each pump aspirates and mixes a plurality of mobile phases from the corresponding mobile phase source group, and supplies the mixed plurality of mobile phases as an intermediate mixed mobile phase to the corresponding flow path, according to claims 1 to 3. The liquid chromatograph according to any one of items. A liquid chromatograph for analyzing a sample,
a plurality of channels respectively corresponding to a plurality of mobile phase source groups;
a supply device that supplies one or more mobile phases from a plurality of mobile phase sources included in each mobile phase source group as an intermediate mixed mobile phase to a channel corresponding to the mobile phase source group;
a selector that selects one of a plurality of intermediate mixed mobile phases respectively flowing in the plurality of channels as a mobile phase for analysis;
The plurality of intermediate mixed mobile phases are selected as the mobile phase for analysis during the analysis period of the sample so that a preset one of the plurality of intermediate mixed mobile phases is selected as the mobile phase for analysis at the start of analysis of the sample. an analysis control unit that controls the selector so that another one of the mixed mobile phases is selected;
a purge control unit that controls at least one of the supply device and the selector so that the plurality of intermediate mixed mobile phases flow through the plurality of flow paths before starting analysis of the sample. . An analysis method using a liquid chromatograph for analyzing a sample,
The liquid chromatograph is
Having a plurality of flow paths respectively corresponding to a plurality of mobile phase source groups,
The analysis method is
supplying one or a plurality of mobile phases from a plurality of mobile phase sources included in each mobile phase source group as an intermediate mixed mobile phase to a channel corresponding to the mobile phase source group during the analysis period of the sample;
During the analysis period of the sample, mixing a plurality of intermediate mixed mobile phases respectively flowing in the plurality of channels to generate a plurality of mixed intermediate mixed mobile phases as a mobile phase for analysis;
The plurality of intermediate mixed mobile phases are adjusted so that the mixing ratio of the plurality of intermediate mixed mobile phases in the mobile phase for analysis is adjusted to a preset initial ratio at the start of analysis of the sample and during the analysis period of the sample adjusting the mixing ratio of the plurality of intermediate mixed mobile phases such that the mixing ratio of the intermediate mixed mobile phases changes over time from the initial ratio;
and generating the mobile phase for analysis such that the mixing ratio of the plurality of intermediate mixed mobile phases is adjusted to the initial ratio before the analysis of the sample is started;
The step of generating the mobile phase for analysis so that the mixing ratio of the plurality of intermediate mixed mobile phases is adjusted to the initial ratio before starting the analysis of the sample includes: is set within a predetermined range including 0, before adjusting the mixing ratio of the plurality of intermediate mixed mobile phases to the initial ratio, the plurality of intermediate An analysis method, comprising supplying a mixed mobile phase to each of the plurality of channels. When the term corresponding to one of the plurality of intermediate mixed mobile phases in the initial ratio is set within a predetermined range including 0, the plurality of intermediate mixed mobile phases before the start of analysis of the sample 9. The analysis method according to claim 8, wherein supplying phases to each of said plurality of channels includes sequentially supplying said plurality of intermediate mixed mobile phases. When the term corresponding to one of the plurality of intermediate mixed mobile phases in the initial ratio is set within a predetermined range including 0, the plurality of intermediate mixed mobile phases before the start of analysis of the sample 9. The analysis method according to claim 8, wherein supplying phases to each of said plurality of channels includes supplying said plurality of intermediate mixed mobile phases in parallel. Further comprising the step of setting the initial ratio and setting a temporal change in the mixing ratio of the plurality of intermediate mixed mobile phases in the mobile phase for analysis during the analysis period of the sample,
adjusting the mixing ratio of the plurality of intermediate mixed mobile phases in the mobile phase for analysis during the analysis period of the sample; and adjusting the mixing ratio of the plurality of intermediate mixed mobile phases to the initial ratio before starting analysis of the sample. The step of generating the mobile phase for analysis to be adjusted includes the plurality of intermediate mixtures flowing through the plurality of channels based on temporal changes in the initial ratio and the mixture ratio set by the setting step The analysis method according to any one of claims 8 to 10, comprising adjusting the mixing ratio of the mobile phase. setting mixing ratios of one or more mobile phases in a plurality of intermediate mixed mobile phases to be respectively flowed through the plurality of channels;
before the analysis of the sample is started and before the plurality of intermediate mixed mobile phases are supplied to the plurality of channels, the plurality of mobile phases in each mobile phase source group are moved according to a predetermined order of the mobile phases; further comprising sequentially supplying to channels corresponding to the phase source group;
The predetermined order of the mobile phases includes a mobile phase that is not used for analysis of the sample, a mobile phase that is not used at the start of analysis of the sample, and a plurality of intermediate mixed mobile phases, and the mixing ratio term is 11. The analysis method according to any one of claims 8 to 10, wherein the mobile phase is included in the smaller mobile phase and the plurality of intermediate mixed mobile phases and the mixing ratio term is in the order of the higher mobile phase. An analysis method using a liquid chromatograph for analyzing a sample,
The liquid chromatograph is
Having a plurality of flow paths respectively corresponding to a plurality of mobile phase source groups,
The analysis method is
supplying one or a plurality of mobile phases from a plurality of mobile phase sources included in each mobile phase source group as an intermediate mixed mobile phase to a channel corresponding to the mobile phase source group during the analysis period of the sample;
a step of selecting one of a plurality of intermediate mixed mobile phases flowing through the plurality of channels as a mobile phase for analysis at the start of analysis of the sample;
selecting another one of the plurality of intermediate mixed mobile phases preset as the mobile phase for analysis during the analysis period of the sample;
and supplying the plurality of intermediate mixed mobile phases to each of the plurality of channels before starting analysis of the sample.

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