WO2020240650A1

WO2020240650A1 - Liquid chromatograph and liquid chromatograph control method

Info

Publication number: WO2020240650A1
Application number: PCT/JP2019/020856
Authority: WO
Inventors: 浩志大橋
Original assignee: 株式会社島津製作所
Priority date: 2019-05-27
Filing date: 2019-05-27
Publication date: 2020-12-03
Also published as: JPWO2020240650A1; JP7120457B2

Abstract

The present invention provides a liquid chromatograph 100 that has a function of switching a plurality of columns and analyzes samples in accordance with a schedule table in which analysis conditions and execution orders of multiple analyses are described, the liquid chromatograph comprising: a schedule reading unit 66 that reads the analysis conditions of each of two analyses successively executed in the schedule table; a column comparison unit 67 that compares the columns used in the two analyses on the basis of the analysis conditions read by the schedule reading unit; an interposed method file creation unit 68 that creates an interposed method file by which, when different columns 321 to 326 are used in the two analyses, a flow rate of a mobile phase poured to columns used for the former analysis is reduced from a first objective flow rate set for the former analysis toward a third objective flow rate which is lower than either of the first objective flow rate and a second objective flow rate set for the subsequent analysis; and a schedule table creation unit 63 that inserts the interposed method file immediately after the former analysis in the schedule table.

Description

Liquid chromatograph and liquid chromatograph control method

The present invention relates to a liquid chromatograph and a liquid chromatograph control method.

The liquid chromatograph consists of a plurality of analysis units such as a pump, a column oven, a detector, and an autosampler, and a control device that controls each analysis unit and processes data collected by the detector. In a liquid chromatograph, a liquid mobile phase (also called an eluent) and a sample injected into the mobile phase are pressurized by a pump and passed through a column, and each component in the sample is filled with a stationary phase (filling) in the column. It is detected separately by the difference in interaction (adsorption, partitioning, ion exchange, size exclusion, etc.) with the mobile phase (also called an agent).

In a liquid chromatograph, one sample may be analyzed under various conditions to search for the optimum analysis conditions for the sample (hereinafter, this is referred to as method scouting). In method scouting, various analytical conditions are set, which consist of a combination of parameters such as mobile phase type, column type, pump flow rate, and column oven temperature for heating the column. Therefore, the liquid chromatograph for performing method scouting is configured so that the parameters can be switched (see Patent Document 1).

Various analysis conditions are described in a file called a "method file" managed by the control device, and stored in the storage unit of the control device. In addition, the control device creates a file called a "schedule table" that describes which analysis conditions are to be executed in what order. The schedule table describes the time series of analysis in the column direction and the sample to be analyzed and its analysis conditions in the row direction, and the above-mentioned method file is cited as the analysis conditions. In method scouting, the control device controls each unit of the liquid chromatograph so that the analysis under each analysis condition is executed at a predetermined timing according to the execution order described in the schedule table.

Japanese Unexamined Patent Publication No. 2013-024603

In method scouting, if the type of column used in a consecutive analysis changes, the objectives defined for the previous analysis towards the column used in the previous analysis until just before the column switch. The mobile phase flows at the flow rate. In general, the target flow rate and the withstand voltage performance of the column are correlated, and the column with high withstand voltage performance is used in the analysis defined for a large target flow rate, and the withstand voltage performance is determined for the analysis with a small target flow rate. A lower column is used. Therefore, if the target flow rate of the subsequent analysis is smaller than the target flow rate of the previous analysis, a pressure exceeding the pressure resistance performance of the column may be applied to the column used for the subsequent analysis. Was sometimes damaged.

The present invention has been made in view of the above points, and an object of the present invention is to damage the columns when switching columns even when method scouting is performed while switching between a plurality of types of columns. Is to reduce.

The first aspect of the present invention made to solve the above problems is
A liquid chromatograph that has a function of switching between a plurality of columns and analyzes a sample according to a schedule table in which each analysis condition and the execution order of the plurality of analyzes are described for a plurality of analyzes.
In the schedule table, for two analyzes executed consecutively, a column comparison unit that compares the columns used in the two analyzes based on the respective analysis conditions, and a column comparison unit.
When the columns used in the two analyzes are different, the flow rate of the mobile phase flowing through the column used in the previous analysis is changed from the first target flow rate defined for the previous analysis to the first target flow rate. And the insertion method file creation unit that creates an insertion method file that decreases toward the third target flow rate, which is lower than any of the second target flow rates specified for the later analysis.
A schedule table creation unit that inserts the insertion method file immediately after the previous analysis in the schedule table, and
With respect to a liquid chromatograph comprising.

The second aspect of the present invention is
A control method for a liquid chromatograph that uses a liquid chromatograph equipped with a function to switch between multiple columns and analyzes samples according to a schedule table that describes the analysis conditions and execution order for multiple analyzes.
In the schedule table, for two consecutive analyzes, a step of comparing the columns used in the two analyzes based on the respective analysis conditions and
When the compared columns are different, the flow rate of the mobile phase flowing through the column used for the previous analysis is determined from the first target flow rate determined for the previous analysis to the first target flow rate and the subsequent analysis. The step of creating an interposition method file that decreases toward a third target flow rate that is lower than any of the obtained second target flow rates, and
The step of inserting the insertion method file immediately after the previous analysis in the schedule table, and
The present invention relates to a liquid chromatograph control method having.

In the liquid chromatograph and the liquid chromatograph control method according to the present invention, when the columns used between two consecutive analyzes are different, the flow rate of the mobile phase flowing through the column used in the previous analysis. To decrease from the first target flow rate defined for the previous analysis to a third target flow rate lower than either the first target flow rate or the second target flow rate defined for the subsequent analysis. Take control. As a result, when the column used for the previous analysis is switched to the column used for the subsequent analysis, the pressure exceeding the pressure resistance performance is not applied to the column used for the subsequent analysis. Therefore, the damage to the column used in the later analysis can be reduced, and the life of the column can be extended.

The figure explaining the liquid chromatograph which concerns on 1st Embodiment of this invention. The flowchart explaining the analysis order of the liquid chromatograph which concerns on this embodiment. The figure which shows the schedule table created in the same embodiment. The figure which shows the example of the screen for setting the information about the column protection method file in the same embodiment. The figure explaining the mobile phase profile of the 1st column protection method file created in the same embodiment. The figure explaining the mobile phase profile of the 2nd column protection method file created in the same embodiment. The figure explaining the liquid chromatograph which concerns on 2nd Embodiment of this invention. The figure explaining the mobile phase profile of the method file for protection of the 1st column created in another embodiment of this invention. The figure explaining the mobile phase profile of the method file for protection of the 1st column created in another embodiment of this invention. Example of column information.

Hereinafter, the liquid chromatograph according to some embodiments of the present invention will be described with reference to the drawings.

(First Embodiment)
FIG. 1 is a schematic configuration diagram of a liquid chromatograph according to the first embodiment. The liquid chromatograph 100 is obtained by the liquid feeding unit 10, the autosampler 20, the column oven 30, the detection unit 40, the system controller 50 that controls each of these units, and the management and detection unit 40 of the analysis work via the system controller 50, respectively. A control device 60 for processing the obtained data is provided. An operation unit 71 including a keyboard and a mouse and a display unit 72 including a display are connected to the control device 60.

A plurality of columns 321 to 326 are provided in the column oven 30, and the plurality of columns 321 to 326 can be switched by the flow

path switching units

31 and 33. In the liquid feeding unit 10, solvent containers 111 to 114 and 121 to 124 containing various mobile phases are connected to the

liquid feeding pumps

171 and 172 via the

degassing units

13 and 14 and the

solvent switching valves

15 and 16. ing. As the mobile phase, water and an aqueous solution (aqueous solvent) obtained by adding various salts to water, and an organic solvent (organic solvent) such as methanol, acetonitrile, and hexane are used. The water-based solvent sucked from any of the solvent containers 111 to 114 and the organic solvent sucked from any of the solvent containers 121 to 124 are mixed with the gradient mixer 18 as necessary, whereby a predetermined value is determined. A mobile phase of composition is prepared.

The mobile phase having a predetermined composition prepared by the liquid feeding unit 10 flows into any one of a plurality of columns 321 to 326 in the column oven 30 via the autosampler 20. At that time, the sample is injected into the mobile phase by the autosampler 20, and the sample passes through the column along with the flow of the mobile phase. In the process, each component in the sample is separated in time, and is sequentially detected by a detection unit 40 provided with a detector 41 such as a mass spectrometer and a photodiode array (PDA) detector.

The control device 60 includes a storage unit 61, an analysis condition setting unit 62, a schedule table creation unit 63, an analysis control unit 64, a data processing unit 65, a schedule reading unit 66, a column comparison unit 67, and a column protection method file creation unit. Has 68. The column protection method file creation unit 68 corresponds to the intervention method file creation unit of the present invention. Further, the actual body of the control device 60 is a computer such as a personal computer or a workstation, and by executing the dedicated control / processing software pre-installed in the computer on the computer, the functions of the above-mentioned parts are achieved.

A general analytical operation in the liquid chromatograph 100 according to the present embodiment will be briefly described. Under the control of the analysis control unit 64, the liquid feed pump 171 sucks a predetermined amount of the mobile phase from any of the mobile phase containers 111 to 114, and the liquid feed pump 172 sucks a predetermined amount of the mobile phase from any of the mobile phase containers 121 to 124, respectively. A predetermined amount of mobile phase is sucked and sent to the gradient mixer 18. The gradient mixer 18 mixes the mobile phases sent from each of the liquid feed pumps 171 and 172 and sends them to the autosampler 20 at a constant flow rate. In the autosampler 20, a sample solution taken from a vial (not shown) is injected into the mobile phase. The sample solution is introduced into any of columns 321 to 326 along the flow of the mobile phase, and the components (sample components) in the sample solution are separated when passing through the column. The eluate containing the sample component thus separated exits from the outlet of the column and is introduced into the detector 41. The detection unit 40 outputs a detection signal according to the amount of the sample component in the eluate introduced into the detector 41. This signal is digitized by an AD converter (not shown), input to the control device 60, and a chromatogram is created by the data processing unit 65 based on the signal.

Subsequently, the characteristic operation of the liquid chromatograph 100 according to the present embodiment will be described with reference to the flowchart shown in FIG. FIG. 2 is a flowchart illustrating the analysis order of the liquid chromatograph at the time of performing method scouting.

When executing method scouting, first, the schedule table creation unit 63 displays a predetermined setting screen on the display unit 72, and accepts input by the user via the operation unit 71 (step S21). On the setting screen, the user can use the name of the sample to be analyzed and its injection amount, the name of the method file used for the analysis, and the name of the data file for saving the analysis results for each of the multiple analyzes performed by method scouting. Enter. In addition, on the setting screen, the user inputs information for adjusting the flow rate of the mobile phase when switching columns when the columns used in two analyzes executed consecutively out of a plurality of analyzes are different. To do. The flow rate adjustment of the mobile phase will be described later.

The schedule table creation unit 63 creates a schedule table that describes the execution order of the plurality of analyzes based on the user's input in step S21, and stores it in the storage unit 61 (step S22). As a result, for example, a schedule table as shown in FIG. 3 is created. When a plurality of analyzes are n analyzes (n: an integer of 2 or more), an n-row schedule table is created.

When the schedule table is created, the schedule reading unit 66 first initializes the variable i corresponding to the number of rows in the schedule table to i = 1 (step S23), and then sets i rows from the storage unit 61 and (i + 1). Read the analysis condition of the row. The column information used for the analysis is not directly described in the schedule table, but is described in the method file cited by the schedule table. Therefore, the schedule reading unit 66 accesses each method file and reads the column information used for the analysis. The column comparison unit 67 compares the analysis conditions of the i-row and the (i + 1) row, and determines whether or not the columns to be used match in both (step S24). The column information is not limited to the embodiment of reading from the method file, and the software may hold the column information as shown in FIG. 8 and determine whether the columns to be used match.

The column used in the analysis of row i and row (i + 1) is the same, such that the only difference in the analysis conditions between row i and row (i + 1) is the temperature change of the column oven 30, and the column is between the two analyzes. If it is not necessary to switch the variable i (Yes in step S24), the variable i is immediately incremented by 1 in step S27 described later.

On the other hand, if the columns used in the analysis of the i-row and the (i + 1) row are different and it is necessary to switch the column between the two analyzes (No in step S24), the column protection method file creation unit 68 may perform the column protection method file creation unit 68. In step S21, the user determines in advance whether or not the flow rate adjustment of the mobile phase is set at the time of column switching (step S25). Then, when the setting for adjusting the flow rate of the mobile phase is made (Yes in step S25), the column protection method file creation unit 68 protects the column used in the analysis executed later in both analyzes. A method file for this purpose (hereinafter, this is referred to as a "column protection method file") is created (step S26).

For example, in the schedule table shown in FIG. 3, in the method files “File 1” and “File 2” cited in Analysis Nos. 1 and 2, column 321 is described as a column used for analysis, and Analysis No. 3 In the method file "File 3" cited in the above, when column 322 is described as the column used for analysis, the column used for analysis is switched when the analysis of analysis number 2 is switched to the analysis of analysis number 3. (Column 321 → Column 322) is required. Therefore, the column protection method file creation unit 68 gradually lowers the same mobile phase as that of the previously executed analysis with respect to the column 321 used in the previously executed analysis until the flow rate reaches a predetermined level. A column protection method file (hereinafter referred to as "first column protection method file") that describes that the liquid is to be sent, and a column 322 used in the analysis to be executed later, and an analysis to be executed after that. Either one of the column protection method files (hereinafter referred to as "second column protection method file") that describes that the same mobile phase is sent while gradually increasing the flow rate until it reaches a predetermined flow rate, or Create both. Hereinafter, the flow rate of the mobile phase lowered in one step or the flow rate of the mobile phase raised in one step is referred to as a “unit flow rate”. In the present embodiment, the user sets in advance in step S21 whether the column protection method file creation unit 68 creates both the first and second column protection method files, or one of them. To do.

For example, FIG. 4 shows an example of the flow rate adjustment screen 721 included in the setting screen displayed on the display unit 72. On the flow rate adjustment screen 721, enter the unit flow rate of the mobile phase described in the check boxes 722 for selecting and setting "adjust the flow rate when switching columns" and the method files for protecting the first and second columns.

Input boxes

723, 724 for inputting and

input boxes

725, 726 for inputting the number of steps are displayed.

In the above flow rate adjustment screen 721, when the check box 722 is checked and no numerical value is input in the input boxes 723 to 726, the column protection method file creation unit 68 is the first. Create both the column protection method file and the second column protection method file. Specifically, the column protection method file creation unit 68 reads out the flow rate (target flow rate) of the mobile phase from the “file 2” in which the conditions for the analysis to be executed earlier are described, and this and the predetermined flow rate. Create a method file for protecting the first column from the default values of flow rate, number of steps, and time per step. Further, the column protection method file creation unit 68 reads out the target flow rate of the mobile phase from the “file 3” in which the conditions for the analysis to be executed later are described, and defaults this, the predetermined flow rate, and the number of steps. Create a method file for protecting the second column from the default value of the value and the time per step. Here, the predetermined flow rate in the first column protection method file (corresponding to the third target flow rate of the present invention) and the predetermined flow rate in the second column protection method file are the purposes of the analysis executed earlier. It is set to a value lower than either the flow rate (corresponding to the first target flow rate of the present invention) or the target flow rate (corresponding to the second target flow rate) of the analysis to be performed later. The predetermined flow rate of the first column protection method file and the predetermined flow rate of the second column protection method file may be the same value or different values.

For example, in "File 2", the target flow rate of the mobile phase is described as 1.7 mL, the default value for the number of steps is 4, the default value for the time per step is 2 minutes, and the predetermined flow rate is 0.1 mL. If there is, the first column protection method file is summed up in 4 steps, with a unit flow rate of 0.4 mL each and a predetermined flow rate (0.1 mL), as in the stepped mobile phase profile shown in FIG. 5A. The file contains an instruction to reduce the flow rate of the mobile phase over 8 minutes.

On the other hand, "File 3" describes that the target flow rate of the mobile phase is 1.0 mL, the default value for the number of steps is 10, the default value for the time per step is 1 minute, and the predetermined flow rate is 0.1 mL. If, the second column protection method file has a unit flow rate of 0.1 mL each in 10 steps until a predetermined flow rate (0.1 mL) is reached, as in the stepped mobile phase profile shown in FIG. 5B. It is a file containing an instruction to reduce the flow rate of the mobile phase over a total of 10 minutes.

Further, on the flow rate adjustment screen 721, when the check box 722 is checked and the numerical values are input to the input boxes 723 to 726, the column protection method file creation unit 68 is set in step S26. , The first and second column protection method files are created from the numerical values input to the input boxes 723 to 726 and the target flow rate of the mobile phase described in the method file cited by the schedule table.

When the first and second column protection method files are created by the column protection method file creation unit 68, the storage unit 61 stores them and registers the set of column protection method files (that is, the storage unit 61). The information between the i-row and the (i + 1) row of the schedule table) is stored.

Next, the schedule reading unit 66 increments the variable i by 1 (step S27) and compares i with n (step S28). If i = n (No in step S28), all the analysis conditions between the rows adjacent to each other in the schedule table having n rows have not been compared, so the process returns to step S24 and the above steps are performed. Execute repeatedly. If i = n (Yes in step S28), the comparison of the two analysis conditions executed consecutively is completed.

When the comparison of the analysis conditions executed consecutively is completed, the schedule table creation unit 63 reads out the information of one set or a plurality of sets of column protection method files created above and its registration destination from the storage unit 61. A new line that cites the column protection method file is registered between the lines on the schedule table designated as the registration destination (step S29).

Subsequently, the analysis control unit 64 executes an analysis according to the schedule table updated as described above (step S30), and when all the analyzes described in the schedule table are executed, a series of analyzes is completed. If all the columns used in each analysis condition described in the schedule table with n rows are the same column, the column protection method file is not created and the schedule table is not updated, so there are the initial n rows. The analysis is performed according to the schedule table.

As described above, according to the liquid chromatograph 100 of the present embodiment, when the columns used in the two analyzes executed consecutively are different, the column protection method file creation unit 68 determines the first and second methods. A column protection method file is created, and the schedule table creation unit 63 registers the first and second column protection method files between the first analysis and the second analysis of the schedule table. Then, when performing the analysis according to the schedule table, when the analysis control unit 64 finishes the previous analysis, the analysis control unit 64 subsequently sends the analysis to the column used for the previous analysis according to the first column protection method file. The flow rate of the mobile phase is gradually reduced by a unit flow rate toward the predetermined flow rate. As a result, when the column used for the previous analysis is switched to the column used for the later analysis, the pressure exceeding the pressure resistance performance is not applied to the column used for the subsequent analysis. Therefore, the damage to the column used in the later analysis can be reduced, and the life of the column can be extended.

Further, the analysis control unit 64 gradually increases the flow rate of the mobile phase flowing through the column used for the subsequent analysis in units of unit flow rates according to the second column protection method file, and then executes the subsequent analysis. As a result, the mobile phase slowly flows into the column used for the later analysis, so that the damage to the column can be reduced.
As described above, the life of the column used for the later analysis can be extended.

(Second Embodiment)
Another second embodiment of the liquid chromatograph according to the present invention will be described with reference to FIG. The same components as those in FIG. 1 are designated by the same reference numerals, and description thereof will be omitted as appropriate.

The liquid chromatograph 101 shown in FIG. 6 includes a pressure sensor 80 and a pressure sensor 81 for detecting the pressure applied to the inlet of the column, in addition to the 100 configurations of the liquid chromatograph shown in FIG. In this embodiment, these pressure sensors will be described as an example of providing these pressure sensors at the outlets of the liquid feed pumps 171 and 172, but the pressure sensor is between the liquid feed pumps 171 and 172 and the inlets of the plurality of columns 321 to 326. It may be provided anywhere as long as it is a flow path.

In the first embodiment described above, an example is shown in which the time per step is predetermined when adjusting the flow rate of the mobile phase flowing through the column. On the other hand, the liquid chromatograph 101 according to the present embodiment is used in the selection column when the flow rate of the mobile phase flowing through the column (hereinafter referred to as “selection column”) is gradually decreased / increased according to the column protection method file. The pressure at the inlet is measured, and the time of each of the steps is determined each time based on the measured value.

Information on the pressure detected by the pressure sensor 80 and the pressure sensor 81 in this embodiment is sent to the control device 70. When the flow rate of the mobile phase flowing through the selection column is reduced, the pressure applied to the inlet of the selection column is lowered accordingly, and then when the flow rate of the mobile phase flowing through the selection column becomes constant, the flow rate of the selection column is reduced. The pressure applied to the inlet gradually stabilizes and shows a constant value. Similarly, when the flow rate of the mobile phase flowing through the selection column is increased, the pressure applied to the inlet of the selection column increases, and then when the flow rate of the mobile phase flowing through the selection column becomes constant, the pressure is increased. The pressure applied to the inlet of the selection column gradually stabilizes and shows a constant value.

Therefore, in the present embodiment, when the liquid transfer is executed according to the column protection method file, the flow rate of the mobile phase is reduced (or increased) by one step, and then the pressure falling (or rising) applied to the inlet of the selected column is increased. When the velocity) falls below a predetermined threshold (or when the pressure applied to the inlet of the selection column stops decreasing (or increasing)), the flow rate of the mobile phase is further decreased (or increased) by one step.

In this way, each time the pressure applied to the inlet of the selection column is actually measured and the flow rate of the mobile phase is decreased (increased) by one step, the flow rate of the mobile phase is further increased after waiting for the pressure to stabilize. The damage to the selected column can be reduced by setting the step down (increase).

(Other embodiments)
In the first and second embodiments described above, an example of a method file for protecting the first column is shown in which the flow rate of the mobile phase flowing through the selected column of the previous analysis is gradually reduced by a unit flow rate. On the other hand, as in the mobile phase profile shown in FIG. 8A, the flow rate of the mobile phase flowing through the selection column of the previous analysis may be reduced in a slope shape.
Similarly, an example of a method file for protecting the second column is shown in which the flow rate of the mobile phase flowing through the selection column of the later analysis is gradually increased by a unit flow rate. On the other hand, as in the mobile phase profile shown in FIG. 8B, the flow rate of the mobile phase flowing through the selection column of the later analysis may be increased in a slope shape.

In the first and second embodiments described above, when it is set to adjust the flow rate at the time of column switching, both the first and second column protection method files are created, but the first You may want to create only the column protection method file.

Further, in the above-mentioned first embodiment, an example is shown in which the user sets in advance whether or not to adjust the flow rate at the time of column switching before starting the analysis. On the other hand, only when the target flow rate specified in the analysis performed earlier is larger than the target flow rate specified in the analysis performed later, out of the two analyzes performed consecutively. The protection method file creation unit 68 may create the first column protection method file, or may create both the first and second column protection method files. Further, in two consecutive analyzes, the column protection method file creation unit 68 creates the first column protection method file only when the inner diameter and / or length of the column used changes. Or you may create both the first and second column protection method files.

Although the embodiments of the present invention have been described in detail with reference to the drawings, those skilled in the art will understand that the embodiments are specific examples of the following embodiments.

(Clause 1) The liquid chromatograph according to the first aspect is
A liquid chromatograph that has a function of switching between a plurality of columns and analyzes a sample according to a schedule table in which each analysis condition and the execution order of the plurality of analyzes are described for a plurality of analyzes.
In the schedule table, for two analyzes executed consecutively, a column comparison unit that compares the columns used in the two analyzes based on the respective analysis conditions, and a column comparison unit.
When the columns used in the two analyzes are different, the flow rate of the mobile phase flowing through the column used in the previous analysis is changed from the first target flow rate defined for the previous analysis to the first target flow rate. And the insertion method file creation unit that creates an insertion method file that gradually decreases toward the third target flow rate, which is lower than any of the second target flow rates specified for the later analysis.
A schedule table creation unit that inserts the insertion method file immediately after the previous analysis in the schedule table, and
May be equipped.

According to the liquid chromatograph described in paragraph 1, when the columns used between two consecutive analyzes are different, the flow rate of the mobile phase flowing through the columns used in the previous analysis is determined. Control is performed so as to decrease from the first target flow rate defined for the previous analysis to a third target flow rate lower than either the first target flow rate or the second target flow rate defined for the subsequent analysis. Do. As a result, when the column used for the previous analysis is switched to the column used for the subsequent analysis, the pressure exceeding the pressure resistance performance is not applied to the column used for the subsequent analysis. Therefore, the damage to the column used in the later analysis can be reduced, and the life of the column can be extended.

(Item 2) In the liquid chromatograph according to the item 1, the insertion method file creation unit creates an insertion method file that steps down from the first target flow rate to the third target flow rate. It may be configured to do so.

According to the liquid chromatograph described in the second item, the pressure applied to the inlet of the column used in the previous analysis is gradually reduced, so that the damage applied to the column can be reduced. Further, when the flow rate of the mobile phase flowing toward the column is reduced, the pressure applied to the column inlet decreases accordingly, and then when the flow rate of the mobile phase flowing through the column becomes constant, the pressure applied to the column inlet also decreases. It gradually stabilizes and shows a constant value. Therefore, by reducing the flow rate of the mobile phase in a stepwise manner, it is possible to reduce the pressure applied to the inlet of the column used in the previous analysis while reducing the pressure, thereby reducing the damage to the column. be able to.

(Item 3) In the liquid chromatograph according to item 1,
The insertion method file creation unit may be configured to create an insertion method file that slopes down from the first target flow rate toward the third target flow rate.

According to the liquid chromatograph described in Section 3, the pressure applied to the inlet of the column used in the previous analysis gradually decreases. In this case, in the configuration in which the flow rate of the mobile phase is reduced in a slope shape, the pressure applied to the inlet of the column used in the previous analysis is not stable, and the flow rate of the mobile phase is reduced. By reducing the flow rate of the mobile phase at a rate of change that does not damage the column, the damage received by the column can be reduced.

(Item 4) In the liquid chromatograph according to item 1,
When the columns used in the two analyzes are different, the insertion method file creating unit gradually decreases from the first target flow rate toward the third target flow rate, and the first insertion method file and the above. Create a second insertion method file that gradually increases from the third target flow rate toward the second target flow rate.
The schedule table creation unit inserts the first intervention method file immediately after the previous analysis in the schedule table, and inserts the second insertion method file immediately before the subsequent analysis in the schedule table. It may be configured to be inserted.

According to the liquid chromatograph described in the fourth item, since the mobile phase slowly flows into the column used for the later analysis, the damage to the column can be further reduced.

(Section 5) The liquid chromatograph control method according to the second aspect is
It is a control method of a liquid chromatograph that uses a liquid chromatograph equipped with a function to switch between multiple columns and analyzes a sample according to a schedule table that describes the analysis conditions and execution order for multiple analyzes.
In the schedule table, for two consecutive analyzes, a step of comparing the columns used in the two analyzes based on the respective analysis conditions, and
When the compared columns are different, the flow rate of the mobile phase flowing through the column used for the previous analysis is determined from the first target flow rate determined for the previous analysis to the first target flow rate and the subsequent analysis. The step of creating an insertion method file that decreases toward a third target flow rate that is lower than any of the obtained second target flow rates, and
The step of inserting the insertion method file immediately after the previous analysis in the schedule table, and
It is good to have.

According to the liquid chromatograph control method described in Section 5, the flow rate of the mobile phase flowing through the column used in the previous analysis when the columns used between the two consecutive analyzes are different. , Control to decrease from the first target flow rate defined for the previous analysis to a third target flow rate lower than either the first target flow rate or the second target flow rate defined for the subsequent analysis. I do. As a result, when the column used for the previous analysis is switched to the column used for the subsequent analysis, the pressure exceeding the pressure resistance performance is not applied to the column used for the subsequent analysis. Therefore, the damage to the column used in the later analysis can be reduced, and the life of the column can be extended.

(Section 6) In the liquid chromatograph control method according to the fifth item, an insertion method file for stepwise lowering from the first target flow rate to the third target flow rate may be created. ..

According to the liquid chromatograph control method described in item 6, the pressure applied to the inlet of the column used in the previous analysis is gradually reduced, so that the damage applied to the column can be reduced. Further, when the flow rate of the mobile phase flowing toward the column is reduced, the pressure applied to the column inlet decreases accordingly, and then when the flow rate of the mobile phase flowing through the column becomes constant, the pressure applied to the column inlet also decreases. It gradually stabilizes and shows a constant value. Therefore, by reducing the flow rate of the mobile phase in a stepwise manner, it is possible to reduce the pressure applied to the inlet of the column used in the previous analysis while reducing the pressure, thereby reducing the damage to the column. be able to.

(Item 7) In the liquid chromatograph control method according to the item 5, an insertion method file for reducing the flow rate from the first target flow rate toward the third target flow rate in a slope shape may be created. ..

According to the liquid chromatograph control method described in paragraph 7, the pressure applied to the inlet of the column used in the previous analysis is gradually reduced. In this case, in the configuration in which the flow rate of the mobile phase is reduced in a slope shape, the pressure applied to the inlet of the column used in the previous analysis is not stable, and the flow rate of the mobile phase is reduced. By reducing the flow rate of the mobile phase at a rate of change that does not damage the column, the damage received by the column can be reduced.

(Item 8) In the liquid chromatograph control method according to item 5, when the columns used in the two analyzes are different, the flow rate is gradually reduced from the first target flow rate to the third target flow rate. A first insertion method file and a second insertion method file that gradually increases from the third target flow rate toward the second target flow rate are created.
Even if the first insertion method file is inserted immediately after the previous analysis in the schedule table and the second insertion method file is inserted immediately before the subsequent analysis in the schedule table. Good.

According to the liquid chromatograph control method described in item 8, the mobile phase slowly flows into the column used for the subsequent analysis, so that the damage to the column can be further reduced.

100, 101 ... Liquid chromatograph 10 ... Liquid feeding section 111-114, 121-124 ...

Solvent container

13, 14 ...

Degassing unit

15, 16 ...

Solvent switching valve

171, 172 ... Liquid feeding pump 18 ... Gradient mixer 20 ... Auto Sampler 30 ...

Column ovens

31, 33 ... Flow path switching units 321 to 326 ... Column 40 ... Detection unit 41 ... Detector 50 ... System controller 60 ... Control device 61 ... Storage unit 62 ... Analysis condition setting unit 63 ... Schedule table creation unit 64 ... Analysis control unit 65 ... Data processing unit 66 ... Schedule reading unit 67 ... Column comparison unit 68 ... Column protection method file creation unit 71 ... Operation unit 72 ...

Display units

80, 81 ... Pressure sensor

Claims

A liquid chromatograph that has a function of switching between a plurality of columns and analyzes a sample according to a schedule table in which each analysis condition and the execution order of the plurality of analyzes are described for a plurality of analyzes.
In the schedule table, for two analyzes executed consecutively, a column comparison unit that compares the columns used in the two analyzes based on the respective analysis conditions, and a column comparison unit.
When the columns used in the two analyzes are different, the flow rate of the mobile phase flowing through the column used in the previous analysis is changed from the first target flow rate defined for the previous analysis to the first target flow rate. And the insertion method file creation unit that creates an insertion method file that gradually decreases toward the third target flow rate, which is lower than any of the second target flow rates specified for the later analysis.
A schedule table creation unit that inserts the insertion method file immediately after the previous analysis in the schedule table, and
A liquid chromatograph characterized by comprising.
The liquid chromatograph according to claim 1, wherein the insertion method file creation unit creates an insertion method file in which the insertion method file is stepwise lowered from the first target flow rate toward the third target flow rate.
The liquid chromatograph according to claim 1, wherein the insertion method file creation unit creates an insertion method file that slopes down from the first target flow rate toward the third target flow rate.
When the columns used in the two analyzes are different, the insertion method file creating unit gradually decreases from the first target flow rate toward the third target flow rate, and the first insertion method file and the above. Create a second insertion method file that gradually increases from the third target flow rate toward the second target flow rate.
The schedule table creation unit inserts the first intervention method file immediately after the previous analysis in the schedule table, and the second intervention method file immediately before the subsequent analysis in the schedule table. The liquid chromatograph according to claim 1, wherein the liquid chromatograph is inserted.
It is a control method of a liquid chromatograph that uses a liquid chromatograph equipped with a function to switch between multiple columns and analyzes a sample according to a schedule table that describes the analysis conditions and execution order for multiple analyzes.
In the schedule table, for two consecutive analyzes, a step of comparing the columns used in the two analyzes based on the respective analysis conditions, and
When the compared columns are different, the flow rate of the mobile phase flowing through the column used for the previous analysis is determined from the first target flow rate determined for the previous analysis to the first target flow rate and the subsequent analysis. The step of creating an insertion method file that decreases toward a third target flow rate that is lower than any of the obtained second target flow rates, and
The step of inserting the insertion method file immediately after the previous analysis in the schedule table, and
A liquid chromatograph control method comprising.
The liquid chromatograph control method according to claim 5, wherein an insertion method file for stepwise lowering from the first target flow rate toward the third target flow rate is created.
The liquid chromatograph control method according to claim 5, wherein an insertion method file for reducing the flow rate from the first target flow rate toward the third target flow rate in a slope shape is created.
When the columns used in the two analyzes are different, the first insertion method file that gradually decreases from the first target flow rate toward the third target flow rate and the second purpose from the third target flow rate. Create a second insertion method file that gradually increases toward the flow rate,
The first intervention method file is inserted immediately after the previous analysis in the schedule table, and the second intervention method file is inserted immediately before the subsequent analysis in the schedule table. The liquid chromatograph control method according to claim 5.