Liquid chromatograph control method and liquid chromatograph

Abstract

In the liquid chromatograph, the conflict between the replacement treatment of the separation column and the reserved analysis action is more easily avoided. A method for controlling a liquid chromatograph provided with a plurality of flow paths that share a liquid delivery device, in which a separation column is provided in each of the plurality of flow paths, the liquid chromatograph is controlled so that the separation column is separated from the flow path in a step after the separation column is connected to the flow path during a process for replacing the separation column, and the separation column is separated from the flow path in the process after the separation column is connected to the flow path. The step in which the liquid feeding device is not used and the treatment in which the flow path that is not the separation column replacement target are used are performed in parallel or without overlapping, and the step in which the liquid feeding device is used and the treatment in which the flow path that is not the separation column replacement target are used are performed without overlapping.

Description

Technical Field

[0001] The invention relates to a control method of a liquid chromatograph and the liquid chromatograph. Background Art

[0002] Liquid chromatograph is an analytical device that uses the following properties to identify components: when a mixed sample solution containing the components to be measured is injected into a separation column to which a solvent is continuously delivered by a liquid delivery pump, the components in the sample interact with the filler and solvent of the separation column according to their chemical properties, and arrive at the detector at different times due to the difference in the interaction of each component. The detector of the liquid chromatograph can be appropriately selected to use a photometer or a mass spectrometer, etc., depending on the purpose of the analysis or the data.

[0003] Among liquid chromatographs, there is also known a liquid chromatograph in which a plurality of separation columns and a liquid feeding pump are connected in parallel (Patent Document 1).

[0004] Prior art literature

[0005] Patent Literature

[0006] Patent Document 1: International Publication No. 2020 / 171240 Pamphlet Summary of the invention

[0007] Problems to be solved by the invention

[0008] However, in the conventional technology, there is a problem that it is difficult to avoid the conflict between the separation column replacement process and the scheduled analysis operation.

[0009] Means for solving problems

[0010] In one example of the control method of the liquid chromatograph of the present invention, in the replacement process of the separation column, the process of using the liquid feeding device in the process after connecting the separation column to the flow path is implemented in a manner that does not overlap with the process of using the flow path that is not the object of the separation column replacement.

[0011] This specification includes the disclosure of Japanese Patent Application No. 2022-174101 which serves as the basis for the priority of the present application.

[0012] Effects of the Invention

[0013] According to the present invention, it is possible to more easily avoid a conflict between a separation column replacement process and a scheduled analysis operation. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Figure 1 This is the structure of the liquid chromatograph according to the present embodiment.

[0015] Figure 2 This is a flowchart showing a method for controlling the liquid chromatograph according to the present embodiment.

[0016] Figure 3 This is a schedule for each separation column in this embodiment.

[0017] Figure 4 It is a schedule table for each separation column in this embodiment.

[0018] Figure 5 It is a schedule table for each separation column in this embodiment.

[0019] Figure 6 It is a schedule table for each separation column in this embodiment.

[0020] Figure 7 This is an example of the separation column replacement process according to the present embodiment. DETAILED DESCRIPTION

[0021] Hereinafter, embodiments of the present invention will be described based on the drawings.

[0022] [Implementation Method 1]

[0023] Figure 1 1 shows the structure of the liquid chromatograph of this embodiment. The liquid chromatograph includes flow paths 104 and 106 to 110. Figure 1 In the example of the embodiment of the present invention, the separation columns 105 are arranged in five flow paths, and in particular, the separation column 105a is arranged in the flow path 106, the separation column 105b is arranged in the flow path 107, the separation column 105c is arranged in the flow path 108, the separation column 105d is arranged in the flow path 109, and the separation column 105e is arranged in the flow path 110. The separation column 105 is not arranged in the flow path 104.

[0024] The start end of each flow path is connected to the flow path switching valve 103, and the end end of each flow path is connected to the flow path switching valve 111. The flow path switching valves 103 and 111 are connected to the flow path switching valve 114. In addition, the flow path switching valve 114 is connected to the detector 112, the liquid delivery device 101 (for example, a pump), and the liquid delivery device 113 (for example, a pump). The liquid delivery devices 101 and 113 can respectively deliver different solvents 115 (which can also be solutions containing solutes such as reagents) via the flow path switching valve 114.

[0025] Here, the flow path switching valve 114 and the liquid feeding device 101 are connected via the sample injection unit 102, and the sample (i.e., the specimen to be examined) can be injected from the sample injection unit 102 into the solvent fed by the liquid feeding device 101. The liquid feeding device 113 feeds a solvent (such as a cleaning solution) that does not require injection of a sample.

[0026] The liquid delivery devices 101 and 113 inject a mixed sample solution containing the components to be measured into the separation column 105. Different contents (fillers and / or solvents) are respectively arranged in the separation column 105. Each component in the sample interacts with the contents of the different separation columns 105 according to its chemical properties, and arrives at the detector 112 at different times according to the difference in the interaction of each component. In this way, the components to be measured can be detected and / or measured. The detector 112 is, for example, a photometer, a mass spectrometer, etc.

[0027] Thus, the liquid chromatograph includes a plurality of flow paths 106 to 110 that share the liquid delivery devices 101 and 113, and separation columns 105 are provided in each of these flow paths. Figure 1 It is understood that there may be a flow path (for example, flow path 104 ) in which the separation column 105 is not provided.

[0028] Although in Figure 1 Although not shown in the figure, a control device for controlling the operation of the liquid chromatograph may also be provided. The control device may also execute the control method of the liquid chromatograph described in this specification to control the operation of the liquid chromatograph.

[0029] The structure of the liquid chromatograph is not limited to Figure 1 The structure shown and the analysis operation of the liquid chromatograph are not limited to the operation described above. A person skilled in the art can appropriately design or change the structure and operation of the liquid chromatograph based on known techniques.

[0030] Figure 7 An example of the separation column replacement process of this embodiment is shown. Figure 7 In the present embodiment, the liquid chromatograph can continue the analysis operation in parallel in the flow path that is not the replacement target of the separation column 105 in order to prevent the entire rapid LC flow from becoming unusable.

[0031] The liquid chromatograph performs the analysis operation of the flow path that is not the object of separation column replacement and the separation column replacement in parallel. Figure 1 As shown in FIG. 1 , the liquid-feeding devices 101 and 113 are required for the separation column replacement process, and are also used in the analysis operation. In a fast LC flow, since a plurality of (e.g., five) flow paths share a set of liquid-feeding devices (liquid-feeding device 101 and liquid-feeding device 113), if the analysis operation of the flow path not to be replaced by the separation column and the entire separation column replacement process are to be performed in parallel, a conflict of the liquid-feeding devices occurs.

[0032] Therefore, in the replacement process of the separation column, the liquid chromatograph is controlled so that in the process after the separation column is connected to the flow path, the process without using the liquid feeding device and the processing of the flow path that is not the object of separation column replacement (for example, analysis action) are performed in parallel, and the process using the liquid feeding device and the processing of the flow path that is not the object of separation column replacement are performed without overlapping.

[0033] exist Figure 7 In the example, the only process that uses the liquid feeding device in the separation column replacement process is the major process "Preparation after separation column replacement". More specifically, in the major process "Preparation after separation column replacement", the minor process "Liquid feeding" is a process that uses the liquid feeding device, and the minor processes "Start of preparation after replacement" and "Completion of preparation after replacement" are processes that do not use the liquid feeding device. The major process "Preparation before separation column replacement" and the major process "Separation column replacement action" are processes that do not use the liquid feeding device.

[0034] The liquid chromatograph can perform, in parallel, a process that does not use a liquid feeding device and an analysis operation of a flow path that is not subject to separation column replacement.

[0035] Furthermore, the liquid chromatograph schedules the process using the liquid feeding device in the nearest empty cycle (for example, a cycle that does not overlap with a process using a flow channel that is not the subject of separation column replacement) at the scheduled time.

[0036] An example of scheduling according to this embodiment will be described below.

[0037] Figure 2 This is a flowchart showing a method for controlling the liquid chromatograph according to the present embodiment.

[0038] in addition, Figure 3 to Figure 6 The schedule table showing various time points of each separation column in this embodiment is prepared for the five separation columns 105a to 105e and the liquid feeding devices 101 and 113.

[0039] Time moves from left to right. Figure 3 to Figure 6 In the figure, the portion corresponding to the time that has passed is indicated in gray. At the time point of each figure, several "analysis" actions have been scheduled. Each analysis action occupies any one of the separation columns 105a to 105e and the liquid delivery device 101 or 113.

[0040] Starts execution based on a request to replace the separation column Figure 2 For example, in Figure 3 At the current time 305, a replacement request 302 is generated for the separation column 105a. First, the liquid chromatograph searches for and specifies a flow channel that is the target of the replacement request (step 201).

[0041] The process using the separation column 105a (e.g., the analysis operation in the separation column 105a) is determined as the process using the flow path 106 that is the subject of separation column replacement. On the other hand, the process using any one of the separation columns 105b to 105e (e.g., the analysis operation in any one of the separation columns 105b to 105e) is determined as the process using any one of the flow paths 107 to 110 that are not the subject of separation column replacement.

[0042] Next, the liquid chromatograph searches for and determines the cycle scheduled in the separation column 105a (if there are multiple cycles, the last cycle among them) (step 202). Figure 3 In the example, the cycle of the analysis action 303 is scheduled.

[0043] Next, the liquid chromatograph temporarily stops scheduling the analysis action after the scheduled cycle (step 203). That is, in the separation column 105a, scheduling a new analysis action after the analysis action 303 is temporarily prohibited. Figure 3 In the diagram, for the separation columns 105b to 105e indicated with "○" as the scheduling availability 301, the state in which scheduling of a new analysis operation is possible is maintained, and for the separation column 105a indicated with "×", scheduling of a new analysis operation is prohibited.

[0044] Next, the liquid chromatograph determines whether the scheduling of the analysis operation after the scheduled cycle is temporarily stopped (step 204). That is, it determines whether the processing of step 203 has been executed. If it has not been temporarily stopped, step 204 is repeatedly executed.

[0045] Next, the liquid chromatograph performs a separation column replacement preparation process on the separation column 105a (step 205). Figure 4 As shown, the last analysis action scheduled in the separation column 105a (the analysis action searched in step 202, for example Figure 3 At the time point when the analysis action 303 is completed, the column replacement preparation 402 and the column replacement action 403 are scheduled and executed as time passes.

[0046] Here, if Figure 4 As shown in (a), the column replacement preparation 402 and the column replacement operation 403 are performed in parallel with the analysis operation using the flow channels 107 to 110 that are not the subject of separation column replacement (of course, they may be performed without overlapping with the above analysis operation).

[0047] In addition, during this period, the analysis operation and the scheduling of the analysis operation can be continued in the flow paths 107 to 110 (the flow paths of the separation columns 105b to 105e) which are not the objects of separation column replacement. Figure 4 In the example, as time goes by Figure 4At the current moment in (a) 409 Figure 4 As the current moment 410 in (b) advances, a new analysis action (eg, analysis action 404 in separation column 105b) is scheduled.

[0048] Next, the liquid chromatograph determines whether the separation column replacement preparatory process is completed (step 206 ). If not, step 206 is repeated.

[0049] When the separation column replacement preparatory process is completed, the liquid chromatograph executes a separation column replacement operation (step 207 ), thereby replacing the separation column 105 a .

[0050] Next, the liquid chromatograph confirms that the separation column replacement operation has been completed (step 208). If it has not been completed, it is also possible to wait until the completion without ending step 208.

[0051] Next, the liquid chromatograph searches for and determines the last analysis action among the scheduled analysis actions for all flow paths (step 209). Figure 4 In the example of (b), the last analysis action among all scheduled analysis actions is analysis action 404 .

[0052] Next, after the analysis action 404 determined in step 209, the liquid chromatograph schedules the separation column replacement preparation process (step 210). Figure 5 As shown, at the current time 506, the future separation column replacement preparation 504 is scheduled. In the separation column replacement preparation 504, the liquid feeding device 101 or 113 is occupied.

[0053] Scheduling the separation column replacement preparation 504 for the liquid delivery device occupies the liquid delivery device, so that for the period of performing the separation column replacement preparation, no analysis action can be scheduled for either the separation column 105a or the other separation columns 105b to 105e. For the period after the separation column replacement preparation 504 is completed, the analysis action can be scheduled (for example, Figure 5 Analysis action 505).

[0054] Next, the liquid chromatograph performs post-replacement preparation processing (step 211). Figure 2 It can be seen that step 211 is executed after the separation column is replaced (ie, after step 208). In other words, the post-replacement preparation process is a process after the column replacement operation 403 (ie, a process after the new separation column is connected to the flow path).

[0055] Initial steps for preparation after separation column replacement ( Figure 7The small process "preparation after replacement", i.e., the process without using the liquid delivery device) includes a process for determining whether the remaining amount of the system reagent is sufficient. The remaining amount of the system reagent can be detected, for example, using a remaining amount detection device provided in the container. In addition, whether the remaining amount of the system reagent is sufficient can be determined, for example, by comparing it with the amount of the system reagent required for the subsequent small process "liquid delivery".

[0056] If the remaining amount of the system reagent is sufficient, the process proceeds to the subsequent step 212. If the remaining amount of the system reagent is insufficient, the separation column replacement preparation process may not be performed. Therefore, a warning message indicating that the remaining amount of the system reagent is insufficient may be output to prompt the user to take action.

[0057] By performing such a determination process, it is possible to avoid or warn that the separation column post-exchange preparation process is not normally performed.

[0058] Liquid delivery process after separation column replacement ( Figure 7 In the small process "liquid delivery", i.e., the process using the liquid delivery device), the liquid chromatograph can identify the type of the newly installed separation column by replacing the separation column, and can also determine the liquid delivery conditions of the system reagent according to the identified type. The content of the liquid delivery conditions can be appropriately defined by those skilled in the art, for example, including flow rate, liquid delivery time, etc. Then, the liquid chromatograph performs liquid delivery of the system reagent according to the determined liquid delivery conditions, and transports the system reagent to the newly installed separation column. According to such control, it is possible to process according to appropriate conditions according to the types of various separation columns.

[0059] The liquid delivery conditions of the system reagent may also be defined as a plurality of modes. In this case, when determining the liquid delivery conditions of the system reagent, one of the plurality of modes is selected according to the type of the newly installed separation column, thereby determining the liquid delivery conditions. In this way, when there are multiple separation columns, it is not necessary to define separate liquid delivery conditions for all separation columns, and the liquid delivery conditions can be set efficiently.

[0060] Furthermore, the liquid feeding step in preparation for the replacement of the separation column may include a step of performing temperature control until the new separation column reaches a predetermined temperature.

[0061] By performing such temperature control, the next analysis operation is performed under more appropriate conditions, and the analysis accuracy and / or analysis efficiency are improved.

[0062] In addition, the liquid delivery process for preparation after the separation column is replaced ( Figure 7 The small process "liquid delivery", that is, the process of using the liquid delivery device) may include: a process of determining whether to perform temperature control of the separation column; and a process of selecting temperature control parameters when temperature control of the separation column is performed.

[0063] For example, the liquid chromatograph may also determine whether to perform temperature control of the separation column according to the type of the newly installed separation column. In addition, when performing temperature control of the separation column, the temperature control parameter may also be selected according to the type of the newly installed separation column.

[0064] By performing such temperature control, the next analysis operation is performed at a more appropriate temperature, thereby improving the analysis accuracy and / or analysis efficiency.

[0065] After step 211, the liquid chromatograph determines whether the separation column replacement preparation process is completed (step 212). If not, step 212 is repeated. Figure 6 When the separation column replacement preparation process is completed, the liquid chromatograph ends. Figure 2 processing.

[0066] In addition, the temporary stop processing (prohibition of scheduling of new analysis actions) occurred in step 203 is Figure 2 is released when the processing of Figure 6 In the example, the scheduling capability 601 changes from "×" to "○" for the separation column 105a, and a new analysis operation can be scheduled for the separation column 105a. Figure 6 (a) at the current time 606 enter Figure 6 At the current time 613 of (b), a new analysis action 611 is scheduled. Figure 4 and Figure 6 It can be seen that the analysis operation 611 is a step after the column replacement operation 403 (that is, a step after a new separation column is connected to the flow path).

[0067] Here, the analysis operation using the flow paths 107 to 110 (the flow paths of the separation columns 105b to 105e) which are not the subject of separation column replacement can be performed before or after the separation column replacement preparation process. On the other hand, the process using the flow path 106 (the flow path of the separation column 105a) which is the subject of separation column replacement cannot be performed before the separation column replacement preparation process, but is performed after the separation column replacement preparation 504, as in the analysis operation 611. In this way, it is possible to prevent the scheduling of the analysis operation for the flow path during the separation column replacement.

[0068] Thus, according to the control method and liquid chromatograph of the present embodiment, the separation column can be replaced without stopping the analysis operation and the scheduling of the analysis operation of the entire fast LC flow, that is, the conflict between the separation column replacement process and the scheduled analysis operation can be avoided more easily.

[0069] According to the control method of a liquid chromatograph and the liquid chromatograph of the present embodiment, the following problems in the conventional liquid chromatograph can be solved.

[0070] In conventional automatic analyzers, when a sample arrives, the analysis items requested for the sample are scheduled, and the analysis operation is performed according to the operation plan determined at that time.

[0071] There are two types of flows in the liquid chromatography section (LC section), HPLC and rapid LC, and each uses a different structure, so it is necessary to schedule the replacement of the separation column to suit each. In HPLC, a method (additional method) is used to schedule the replacement of the separation column after the last analysis action that has been scheduled.

[0072] During scheduling, the usage timing of each unit used in the target analysis item and the usage amount of each consumable are reserved. The device manages the validity period and remaining number of uses of the separation column, so after the separation column becomes unusable, the analysis operation is not registered for the target stream line.

[0073] Therefore, in the replacement of the separation column based on the judgment of the apparatus, there will be no conflict between the separation column replacement process and the scheduled analysis operation.

[0074] On the other hand, the separation column replacement based on user judgment is not related to the validity period and the remaining number of uses of the target separation column, but is requested at a user's arbitrary timing. Therefore, when there is a request for separation column replacement, sometimes an analysis action has been registered in the target flow line, which conflicts with the separation column replacement process.

[0075] Since the separation column is part of the flow line, the same unit as that for the analysis operation is used for separation column replacement, so separation column replacement and analysis operation cannot be performed simultaneously in the target flow line.

[0076] As described above, in the conventional technology, there is a problem that it is difficult to avoid the conflict between the separation column replacement process and the scheduled analysis operation.

[0077] Therefore, it is beneficial to avoid a conflict between the separation column replacement process and the scheduled analysis operation when the separation column replacement is requested during operation.

[0078] According to the control method of a liquid chromatograph and the liquid chromatograph of the present embodiment, it is possible to more easily avoid a conflict between a separation column replacement process and a scheduled analysis operation.

[0079] For example, in the scheduling of separation column replacement suitable for the structure of rapid LC, it is possible to schedule without canceling the analysis. Therefore, the separation column can be replaced without stopping the examination, the increase in the consumption of specimens and consumables can be avoided, and the reduction in the throughput of the device can be suppressed, which can ultimately help reduce the waiting time of patients and smooth the work of medical staff.

[0080] Explanation of symbols

[0081] 101…Liquid delivery device

[0082] 102…Sample injection unit

[0083] 103…Flow path switching valve

[0084] 105 (105a~105e)…Separation column

[0085] 104, 106~110…Flow path

[0086] 111…Flow path switching valve

[0087] 112…Detector

[0088] 113…Liquid delivery device

[0089] 114…Flow path switching valve

[0090] 115…Solvent

[0091] 301…Can it be dispatched?

[0092] 302…Replace Request

[0093] 303…Analysis Action

[0094] 305…current moment

[0095] 402…Preparation before column replacement

[0096] 403…Column replacement action

[0097] 404…Analysis action (processing using a flow path that is not the target of separation column replacement)

[0098] 409...Current time

[0099] 410…current moment

[0100] 504…Preparation after separation column replacement (processing after connecting a new separation column to the flow path)

[0101] 505…Analysis action (processing using a flow path that is not the subject of separation column replacement)

[0102] 506…current moment

[0103] 601…Can it be dispatched?

[0104] 606…current moment

[0105] 611…Analysis Action

[0106] 613…the present moment.

[0107] All publications, patents and patent applications cited in this specification are incorporated herein by reference.

Claims

1. A method for controlling a liquid chromatograph, wherein the liquid chromatograph comprises a plurality of flow paths sharing a liquid feeding device, wherein a separation column is provided in each of the plurality of flow paths, wherein: During the replacement process of the separation column, the liquid chromatograph is controlled so that, in the process after the separation column is connected to the flow path, the process without using the liquid feeding device is performed in parallel or non-overlappingly with the process using the flow path that is not the object of separation column replacement, and the process using the liquid feeding device is performed non-overlappingly with the process using the flow path that is not the object of separation column replacement.

2. The control method of the liquid chromatograph according to claim 1, characterized in that: In the replacement process of the separation column, the process using the flow path that is not the object of separation column replacement is performed before or after the process using the liquid feeding device, and the process using the flow path that is the object of separation column replacement is performed after the process using the liquid feeding device.

3. The control method of the liquid chromatograph according to claim 1, characterized in that: The above-mentioned steps without using a liquid feeding device include a step of determining whether the remaining amount of the system reagent is sufficient after replacing the separation column.

4. The control method of the liquid chromatograph according to claim 1, characterized in that: The process using the liquid delivery device includes: A step of determining a liquid feeding condition of a system reagent according to the type of a separation column newly installed by replacing the separation column; and A step of supplying a system reagent to the newly installed separation column based on the determined liquid supply conditions.

5. The control method of the liquid chromatograph according to claim 4, characterized in that: The delivery conditions of system reagents are defined as multiple modes, In the step of determining the liquid feeding condition of the system reagent, the liquid feeding condition is determined by selecting one of the plurality of patterns according to the type of the separation column newly installed by replacing the separation column.

6. The control method of liquid chromatograph according to claim 1, characterized in that: The step using the liquid feeding device includes a step of performing temperature control until the separation column reaches a predetermined temperature after replacing the separation column.

7. The control method of liquid chromatograph according to claim 1, characterized in that: The process using the liquid delivery device includes: A step of determining whether to perform temperature control of the separation column after replacing the separation column; and When the temperature of a separation column is controlled, a step of selecting temperature control parameters is performed.

8. A liquid chromatograph comprising a plurality of flow paths sharing a common liquid feeding device, wherein a separation column is provided in each of the plurality of flow paths, wherein: In the replacement process of the separation column, in the process after the separation column is connected to the flow path, the process without using the liquid feeding device is implemented in parallel or non-overlappingly with the process using the flow path that is not the object of separation column replacement, and the process using the liquid feeding device is implemented non-overlappingly with the process using the flow path that is not the object of separation column replacement.

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