JP7120457B2 - Liquid chromatograph and liquid chromatograph control method - Google Patents

Description

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

A liquid chromatograph is composed of a plurality of analysis units such as a pump, a column oven, a detector, an autosampler, etc., and a controller for controlling each analysis unit and processing data collected by the detector. In liquid chromatography, a liquid mobile phase (also called an eluent) and a sample injected into the mobile phase are pressurized by a pump to pass through the column, and each component in the sample is transferred to the stationary phase (packing) in the column. agents) and interactions with the mobile phase (adsorption, partition, ion exchange, size exclusion, etc.).

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

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

Japanese Patent Application Laid-Open No. 2013-024603

In method scouting, when the type of column used in consecutively performed analyzes changes, the purpose defined for the previous analysis is directed to the column used in the previous analysis until just before switching columns. The mobile phase is run at the flow rate. In general, there is a correlation between the target flow rate and the pressure resistance of the column. In analyzes where the target flow rate is set at a high value, a column with high pressure resistance is used, and in analysis where the target flow rate is set at a low value, a column with high pressure resistance is used. A low column is used. Therefore, if the target flow rate for the subsequent analysis is smaller than the target flow rate for the previous analysis, the column used for the subsequent analysis may be subjected to pressure exceeding the pressure resistance performance of the column. was sometimes damaged.

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

A first aspect of the present invention, which has been made to solve the above problems,
A liquid chromatograph that has a function of switching a plurality of columns and analyzes a sample according to a schedule table that describes the analysis conditions and the execution order of the multiple analyzes for multiple analyzes,
a column comparison unit that compares the columns used in the two analyses, based on the respective analysis conditions, for the two analyses, which are performed consecutively in the schedule table;
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 determined for the previous analysis to the first target flow rate, and an interpolated method file creation unit that creates an interpolated method file that decreases toward a third target flow rate that is lower than any of the second target flow rates defined for the subsequent analysis;
a schedule table creation unit that inserts the interposed method file immediately after the previous analysis in the schedule table;
relates to a liquid chromatograph comprising

Moreover, the second aspect of the present invention is
A method for controlling 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,
comparing the columns used in the two analyses, based on the respective analytical conditions, for the two analyses, which are performed consecutively, in the schedule table;
When the compared columns are different, the flow rate of the mobile phase for the column used in the previous analysis is determined from the first target flow rate determined for the previous analysis, and the first target flow rate for the subsequent analysis. creating an interpolation method file that decreases toward a third target flow rate that is lower than any of the second target flow rates obtained;
inserting the interposed method file immediately after the previous analysis in the schedule table;
It relates to a liquid chromatograph control method having

In the liquid chromatograph and liquid chromatograph control method according to the present invention, when the columns used are different between two analyses, which are performed in succession, the flow rate of the mobile phase flowing to the column used for the previous analysis is from the first target flow rate defined for the previous analysis to a third target flow rate that is lower than either the first target flow rate or the second target flow rate defined for the subsequent analysis. control. As a result, when the column used for the previous analysis is switched to the column used for the subsequent analysis, the column used for the subsequent analysis is not subjected to pressure exceeding its pressure resistance performance. Therefore, it is possible to reduce the damage to the column used in the subsequent analysis and extend the life of the column.

BRIEF DESCRIPTION OF THE DRAWINGS The figure explaining the liquid chromatograph which concerns on 1st Embodiment of this invention. 4 is a flowchart for explaining the analysis order of the liquid chromatograph according to the embodiment; The figure which shows the schedule table produced in the same embodiment. FIG. 4 is a diagram showing an example of a screen for setting information about a column protection method file in the same embodiment; The figure explaining the mobile-phase profile of the method file for 1st column protection created in the same embodiment. The figure explaining the mobile-phase profile of the method file for 2nd column protection 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 1st column protection created in other embodiment of this invention. The figure explaining the mobile-phase profile of the method file for 1st column protection created in other embodiment of this invention. Example of column information.

Hereinafter, liquid chromatographs 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. This liquid chromatograph 100 includes a liquid transfer unit 10, an autosampler 20, a column oven 30, a detection unit 40, a system controller 50 that controls each of these units, and management of analysis work via the system controller 50 and detection by the detection unit 40. A controller 60 is provided for processing the received data. The controller 60 is connected to an operation unit 71 including a keyboard and a mouse, and a display unit 72 including a display.

A plurality of columns 321 to 326 are provided in the column oven 30 , and the plurality of columns 321 to 326 are switched by flow path switching units 31 and 33 . In the liquid transfer unit 10, solvent containers 111 to 114 and 121 to 124 containing various mobile phases are connected to liquid transfer pumps 171 and 172 via degassing units 13 and 14 and solvent switching valves 15 and 16. ing. As the mobile phase, water, aqueous solutions obtained by adding various salts to water (aqueous solvents), and organic solvents (organic solvents) such as methanol, acetonitrile, and hexane are used. The aqueous solvent sucked from any one of the solvent containers 111 to 114 and the organic solvent sucked from any one of the solvent containers 121 to 124 are mixed by the gradient mixer 18 as necessary, thereby obtaining a predetermined A mobile phase of composition is prepared.

A mobile phase having a predetermined composition prepared in the liquid feeding section 10 flows through the autosampler 20 into any one of the columns 321 to 326 in the column oven 30 . 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 this process, each component in the sample is temporally separated and sequentially detected by a detection unit 40 provided with a detector 41 such as a mass spectrometer or 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. 68. The column protection method file creation unit 68 corresponds to the interposition method file creation unit of the present invention. The control device 60 is actually a computer such as a personal computer or a workstation, and by executing dedicated control/processing software pre-installed in the computer, the functions of the respective units described above are achieved.

A general analysis operation in the liquid chromatograph 100 according to this embodiment will be briefly described. Under the control of the analysis control unit 64, the liquid-sending pump 171 aspirates a predetermined amount of the mobile phase from any one of the mobile phase containers 111 to 114, and the liquid-sending pump 172 draws a predetermined amount from each of the mobile phase containers 121 to 124. A predetermined amount of mobile phase is aspirated and sent to the gradient mixer 18 . The gradient mixer 18 mixes the mobile phases sent from the liquid sending pumps 171 and 172 and sends them to the autosampler 20 at a constant flow rate. In the autosampler 20, a sample liquid collected from a vial (not shown) is injected into the mobile phase. The sample liquid is introduced into one of the columns 321 to 326 along with the flow of the mobile phase, and components (sample components) in the sample liquid are separated when passing through the columns. The eluate containing the sample components thus separated exits the outlet of the column and is introduced into the detector 41 . The detector 40 outputs a detection signal corresponding to the amount of sample components 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 in the data processing section 65 based on the signal.

Next, a characteristic operation of the liquid chromatograph 100 according to this embodiment will be described with reference to the flowchart shown in FIG. FIG. 2 is a flow chart for explaining the order of liquid chromatograph analysis during execution of method scouting.

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

Based on the user's input in step S21, the schedule table creation unit 63 creates a schedule table describing the execution order of the multiple analyzes and stores it in the storage unit 61 (step S22). As a result, a schedule table such as that shown in FIG. 3, for example, is created. When the multiple times of analysis is n times of analysis (n: an integer equal to or greater than 2), a schedule table with n lines is created.

When the schedule table is created, the schedule reading unit 66 first initializes a variable i corresponding to the number of rows in the schedule table to i=1 (step S23), and then reads i rows and (i+1) from the storage unit 61. Read analysis condition of row. Information on columns used for analysis is not directly described in the schedule table, but is described in the method file referred to by the schedule table. Therefore, the schedule reading unit 66 accesses each method file and reads information on columns used for 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 between them (step S24). Note that the column information is not limited to the embodiment in which the column information is read 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 as 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 used between both analyses. (Yes in step S24), the process immediately proceeds to step S27, which will be described later, to increase the variable i by one.

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

For example, in the schedule table shown in FIG. If column 322 is described as the column used for analysis in "file 3", which is the method file cited in , when switching from the analysis of analysis number 2 to the analysis of analysis number 3, the column used for analysis is switched (Column 321→Column 322) is required. Therefore, the column protection method file creating unit 68 gradually lowers the same mobile phase used in the previously performed analysis to a predetermined flow rate for the column 321 used in the previously performed analysis. A column protection method file (hereinafter referred to as a "first column protection method file") that describes liquid transfer, and a column 322 used in the analysis that will be performed later. Either one of the column protection method file (hereinafter referred to as the "second column protection method file") describing that the same mobile phase is fed while increasing it stepwise until it reaches a predetermined flow rate, or create both. Hereinafter, the flow rate of the mobile phase that is decreased in one step or the flow rate of the mobile phase that is increased in one step is referred to as “unit flow rate”. In the present embodiment, whether the column protection method file creation unit 68 creates both the first and second column protection method files or only one of them is set in advance by the user in step S21. do.

For example, FIG. 4 shows an example of a flow rate adjustment screen 721 included in the setting screen displayed on the display unit 72. As shown in FIG. On the flow rate adjustment screen 721, a check box 722 for selecting and setting "Adjust the flow rate when switching columns" is input, and the unit flow rate of the mobile phase described in each of the first and second column protection method files is entered. Input boxes 723, 724 for entering the number of steps and input boxes 725, 726 for entering the number of steps are displayed.

In the flow rate adjustment screen 721, when the check box 722 is checked and no numerical values are entered in the input boxes 723 to 726, the column protection method file creation unit 68 performs the first Create both a column protection method file and a 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 first are described. Create a method file for first column protection from default values for flow rate, number of steps, and default values for time per step. In addition, the column protection method file creation unit 68 reads out the target flow rate of the mobile phase from "file 3" in which the conditions for the analysis to be executed later are described, Create a second column protection method file from the value and the default value of 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 performed first. It is set to a value lower than both the flow rate (corresponding to the first target flow rate of the present invention) and the target flow rate of the analysis to be performed later (corresponding to the second target flow rate). 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, "File 2" describes the target flow rate of the mobile phase 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. In some cases, the method file for protecting the first column has a unit flow rate of 0.4 mL, such as the stepped mobile phase profile shown in FIG. The file contains instructions to reduce the mobile phase flow rate over 8 minutes.

On the other hand, "File 3" describes the target flow rate of the mobile phase as 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. , the method file for protecting the second column, like the stepped mobile phase profile shown in FIG. The file contains instructions to reduce the flow rate of the mobile phase over a total of 10 minutes.

In addition, when the check box 722 is checked in the flow rate adjustment screen 721 and numerical values are entered in the input boxes 723 to 726, the column protection method file creation unit 68 in step S26 , the first and second column protection method files are created from the values entered in the input boxes 723 to 726 and the target flow rate of the mobile phase described in the method file referred to 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 also specifies the registration destination of the set of column protection method files (that is, Stores information between line i and line (i+1) of the schedule table.

Next, the schedule reading unit 66 increments the variable i by 1 (step S27) and compares i with n (step S28). If i is not equal to n (No in step S28), the comparison of the analysis conditions between adjacent rows of the schedule table with n rows has not been performed, so the process returns to step S24 to perform the above steps. Execute repeatedly. If i=n (Yes in step S28), the continuously executed comparison of two analysis conditions ends.

When the comparison of the analysis conditions that are continuously executed is completed, the schedule table creation unit 63 reads out from the storage unit 61 one or a plurality of pairs of column protection method files created above and information on their registration destinations. A new line that references 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 analysis according to the updated schedule table (step S30), and when all the analyzes described in the schedule table are executed, a series of analyzes ends. In addition, if the columns used for each analysis condition described in the schedule table with n rows are all the same columns, the method file for column protection is not created and the schedule table is not updated. Analysis is performed according to the schedule table.

As described above, according to the liquid chromatograph 100 of the present embodiment, when different columns are used in two analyses, which are performed in succession, the column protection method file creation unit 68 creates the first and second A column protection method file is created, and the schedule table creating unit 63 registers the first and second column protection method files in the schedule table between the previous analysis and the subsequent analysis. When the analysis is performed according to the schedule table, after the previous analysis is completed, the analysis control unit 64 follows the first column protection method file to flow the column used for the previous analysis. The flow rate of the mobile phase is decreased stepwise by 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 subsequent analysis, the column used for the subsequent analysis is not subjected to pressure exceeding its pressure resistance. As a result, damage to the column used in subsequent analysis can be reduced, and the life of the column can be lengthened.

In addition, the analysis control unit 64 increases the flow rate of the mobile phase flowing through the column used for the subsequent analysis stepwise by unit flow rate according to the second column protection method file, and then executes the subsequent analysis. As a result, the mobile phase gently flows into the column to be used for subsequent analysis, so that damage to the column can be reduced.
As described above, the life of the column used for subsequent 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 denoted by the same reference numerals, and description thereof is omitted as appropriate.

The liquid chromatograph 101 shown in FIG. 6 includes pressure sensors 80 and 81 for detecting the pressure applied to the inlet of the column in addition to the structure 100 of the liquid chromatograph shown in FIG. In this embodiment, an example in which these pressure sensors are provided at the outlets of the liquid-sending pumps 171 1 and 172 2 will be described. It may be provided anywhere as long as it is a flow path.

In the above-described first embodiment, an example was shown in which the time per step was determined in advance when adjusting the flow rate of the mobile phase flowing through the column. On the other hand, in the liquid chromatograph 101 according to the present embodiment, when the flow rate of the mobile phase flowing through the column (hereinafter referred to as "selected column") is stepwise decreased/increased according to the column protection method file, the selected column The pressure at the inlet is measured and the time for each step is determined accordingly based on the measured value.

In this embodiment, pressure information detected by the pressure sensors 80 and 81 is sent to the control device 70 . When the flow rate of the mobile phase flowing through the selection column is decreased, the pressure applied to the inlet of the selection column decreases accordingly. After that, when the flow rate of the mobile phase flowing through the selection column becomes constant, The pressure applied to the inlet gradually becomes stable 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 accordingly. The pressure applied to the inlet of the selected column also gradually becomes stable and shows a constant value.

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

Thus, 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 pressure is waited for to stabilize before the flow rate of the mobile phase is increased by one more step. The stepwise reduction (increase) configuration can reduce the damage to the selected column.

(Other embodiments)
In the above-described first and second embodiments, an example of the first column protection method file for stepwise decreasing the flow rate of the mobile phase flowing through the selected column of the previous analysis by unit flow rate was shown. On the other hand, the flow rate of the mobile phase flowing through the selected column of the previous analysis may be decreased in a slope like the mobile phase profile shown in FIG. 7A.
Similarly, an example of a second column protection method file for stepwise increasing the flow rate of the mobile phase flowing through the selected column for subsequent analysis by unit flow rate is shown. On the other hand, as in the mobile phase profile shown in FIG. 7B, the flow rate of the mobile phase flowing to the selected column for subsequent analysis may be increased in a sloped manner.

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. Alternatively, only the column protection method file may be created.

Moreover, in the first embodiment described above, an example was shown in which the user presets whether or not to perform flow rate adjustment at the time of column switching before starting analysis. On the other hand, of two analyses, which are run in succession, only if the target flow rate determined in the earlier run is greater than the target flow rate determined in the later run, the column The protection method file creation unit 68 may create a first column protection method file, or create both first and second column protection method files. Furthermore, 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 is changed in the two analyses, which are performed in succession. Alternatively, both the first and second column protection method files may be created.

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 aspects.

(Section 1) The liquid chromatograph according to the first aspect is
A liquid chromatograph that has a function of switching a plurality of columns and analyzes a sample according to a schedule table that describes the analysis conditions and the execution order of the multiple analyzes for multiple analyzes,
a column comparison unit that compares the columns used in the two analyses, based on the respective analysis conditions, for the two analyses, which are performed consecutively in the schedule table;
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 determined for the previous analysis to the first target flow rate, and an interpolation method file creation unit that creates an interpolation method file that gradually decreases toward a third target flow rate that is lower than any of the second target flow rate defined for the subsequent analysis;
a schedule table creation unit that inserts the interposed method file immediately after the previous analysis in the schedule table;
may be provided.

According to the liquid chromatograph according to item 1, when the columns used between two analyzes performed in succession are different, the flow rate of the mobile phase flowing to the column used for the previous analysis is Control to decrease from the first target flow rate determined for the previous analysis to a third target flow rate that is lower than either the first target flow rate or the second target flow rate determined for the subsequent analysis. conduct. As a result, when the column used for the previous analysis is switched to the column used for the subsequent analysis, the column used for the subsequent analysis is not subjected to pressure exceeding its pressure resistance performance. As a result, damage to the column used in subsequent analysis can be reduced, and the life of the column can be lengthened.

(Section 2) In the liquid chromatograph according to Section 1, the interpolation method file creation unit creates the interpolation method file that decreases stepwise from the first target flow rate toward the third target flow rate. may be configured to

According to the liquid chromatograph described in item 2, since the pressure applied to the inlet of the column used for the previous analysis is gradually lowered, damage applied to the column can be reduced. In addition, when the flow rate of the mobile phase flowing into the column is decreased, the pressure applied to the column inlet decreases accordingly. It gradually stabilizes and shows a constant value. Therefore, by stepwise decreasing the flow rate of the mobile phase, the pressure applied to the inlet of the column used in the previous analysis can be decreased while stabilizing the pressure, thereby reducing damage to the column. be able to.

(Section 3) In the liquid chromatograph according to Section 1,
The intervention method file creation unit may be configured to create an intervention method file that decreases the first target flow rate toward the third target flow rate in a slope-like manner.

According to the liquid chromatograph described in item 3, the pressure applied to the inlet of the column used for the previous analysis is gently lowered. In this case, in a configuration in which the flow rate of the mobile phase is decreased in a slope-like manner, the pressure applied to the inlet of the column used for the previous analysis is not stabilized, and the flow rate of the mobile phase is decreased. By lowering the flow rate of the mobile phase at a rate that does not damage the column, damage to the column can be reduced.

(Section 4) In the liquid chromatograph according to Section 1,
when the columns used in the two analyses, are different, the interposition method file creation unit gradually decreases the first interposition method flow rate toward the third target flow rate; Create a second interpolation 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 interposed method file immediately after the previous analysis in the schedule table, and inserts the second interposed method file immediately before the subsequent analysis in the schedule table. It may be configured for insertion.

According to the liquid chromatograph described in item 4, since the mobile phase gently flows into the column used for subsequent analysis, damage to the column can be further reduced.

(Section 5) In the liquid chromatograph control method according to the second aspect,
A method for controlling 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,
comparing the columns used in the two analyses, based on the respective analytical conditions, for the two analyses, which are performed consecutively, in the schedule table;
When the compared columns are different, the flow rate of the mobile phase for the column used in the previous analysis is determined from the first target flow rate determined for the previous analysis, and the first target flow rate for the subsequent analysis. creating an interpolation method file that decreases toward a third target flow rate that is lower than any of the second target flow rates obtained;
inserting the interposed method file immediately after the previous analysis in the schedule table;
should have

According to the liquid chromatograph control method according to item 5, when the columns used between two analyses, which are performed in succession, are different, the flow rate of the mobile phase flowing to the column used for the previous analysis from the first target flow rate defined for the previous analysis to a third target flow rate that is lower than either the first target flow rate or the second target flow rate defined for the subsequent analysis. control. As a result, when the column used for the previous analysis is switched to the column used for the subsequent analysis, the column used for the subsequent analysis is not subjected to pressure exceeding its pressure resistance performance. As a result, damage to the column used in subsequent analysis can be reduced, and the life of the column can be lengthened.

(Section 6) In the liquid chromatograph control method described in Section 5, an intervening method file may be created for decreasing stepwise from the first target flow rate toward the third target flow rate. .

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 gently lowered, so that the damage applied to the column can be reduced. In addition, when the flow rate of the mobile phase flowing into the column is decreased, the pressure applied to the column inlet decreases accordingly. It gradually stabilizes and shows a constant value. Therefore, by stepwise decreasing the flow rate of the mobile phase, the pressure applied to the inlet of the column used in the previous analysis can be decreased while stabilizing the pressure, thereby reducing damage to the column. be able to.

(Section 7) In the liquid chromatograph control method described in Section 5, an intervening method file may be created to reduce the first target flow rate in a sloped manner toward the third target flow rate. .

According to the liquid chromatograph control method described in item 7, the pressure applied to the inlet of the column used for the previous analysis is gently lowered. In this case, in a configuration in which the flow rate of the mobile phase is decreased in a slope-like manner, the pressure applied to the inlet of the column used for the previous analysis is not stabilized, and the flow rate of the mobile phase is decreased. By lowering the flow rate of the mobile phase at a rate that does not damage the column, damage to the column can be reduced.

(Section 8) In the liquid chromatograph control method according to Section 5, when the columns used in the two analyzes are different, the first target flow rate is gradually decreased toward the third target flow rate. Creating a first interpolation method file and a second interpolation method file that gradually increases from the third target flow rate toward the second target flow rate,
inserting the first interposed method file immediately after the previous analysis in the schedule table and inserting the second interposed method file immediately before the subsequent analysis in the schedule table; good.

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

DESCRIPTION OF SYMBOLS 100, 101... Liquid chromatograph 10... Liquid sending part 111-114, 121-124... Solvent container 13, 14... Degassing unit 15, 16... Solvent switching valve 171, 172... Liquid sending pump 18... Gradient mixer 20... Auto Sampler 30 Column ovens 31, 33 Flow path switching units 321 to 326 Column 40 Detecting 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 unit 80, 81 Pressure sensor

Claims (8)

A liquid chromatograph that has a function of switching a plurality of columns and analyzes a sample according to a schedule table that describes the analysis conditions and the execution order of the multiple analyzes for multiple analyzes,
a column comparison unit that compares the columns used in the two analyses, based on the respective analysis conditions, for the two analyses, which are performed consecutively in the schedule table;
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 determined for the previous analysis to the first target flow rate, and an interpolation method file creation unit that creates an interpolation method file that gradually decreases toward a third target flow rate that is lower than any of the second target flow rate defined for the subsequent analysis;
a schedule table creation unit that inserts the interposed method file immediately after the previous analysis in the schedule table;
A liquid chromatograph comprising: 2. The liquid chromatograph according to claim 1, wherein said interpolation method file creation unit creates an interpolation method file for stepwise reduction from said first target flow rate toward said third target flow rate. 2. The liquid chromatograph according to claim 1, wherein said interpolation method file creating unit creates an interpolation method file in which said first target flow rate is decreased toward said third target flow rate in a sloped manner. when the columns used in the two analyses, are different, the interposition method file creation unit gradually decreases the first interposition method flow rate toward the third target flow rate; Create a second interpolation 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 interposed method file immediately after the previous analysis in the schedule table, and inserts the second interposed method file immediately before the subsequent analysis in the schedule table. 2. The liquid chromatograph according to claim 1, wherein the liquid chromatograph is inserted. A method for controlling 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,
comparing the columns used in the two analyses, based on the respective analytical conditions, for the two analyses, which are performed consecutively, in the schedule table;
When the compared columns are different, the flow rate of the mobile phase for the column used in the previous analysis is determined from the first target flow rate determined for the previous analysis, and the first target flow rate for the subsequent analysis. creating an interpolation method file that decreases toward a third target flow rate that is lower than any of the second target flow rates obtained;
inserting the interposed method file immediately after the previous analysis in the schedule table;
A liquid chromatograph control method comprising: 6. The liquid chromatograph control method according to claim 5, wherein an intervening method file for decreasing stepwise from the first target flow rate toward the third target flow rate is created. 6. The method of controlling a liquid chromatograph according to claim 5, wherein an intervening method file for decreasing the first target flow rate in a sloped manner toward the third target flow rate is created. When the columns used in the two analyzes are different, a first interpolation method file that gradually decreases from the first target flow rate toward the third target flow rate, and from the third target flow rate to the second target flow rate Create a second interpolated method file that gradually increases towards the flow rate,
The first interposed method file is inserted in the schedule table immediately after the previous analysis, and the second interposed method file is inserted in the schedule table just before the subsequent analysis. The liquid chromatograph control method according to claim 5.

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