Chromatography device
By introducing a separation device and an automated condition setting unit into the chromatographic apparatus, the problem of excessively long separation and analysis time for target components in the prior art is solved, realizing an automated separation and analysis process and improving efficiency.
Patent Information
- Application Number
- CN202410814876.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Priority Date
- 2023-07-19
- Filing Date
- 2024-06-24
- Publication Date
- 2025-01-21
AI Technical Summary
When using a chromatographic apparatus to separate and analyze target components, existing technologies require confirmation of the separation container information on the separation result screen, which increases working time.
By employing a combination of a separation device, a separation and analysis condition setting unit, a separation execution unit, and an analysis execution unit, the separation and analysis conditions of the target component are automatically set and executed, reducing the number of manual verification steps.
By automating the setting and execution of extraction and analysis conditions, the time required for target component extraction and analysis is reduced, thus improving efficiency.
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Figure CN119335109A_ABST
Abstract
Description
Technical Field
[0001] The invention relates to a chromatography device. Background Art
[0002] One type of liquid chromatograph is a fractionating liquid chromatograph (e.g., Patent Document 1). In the fractionating liquid chromatograph, a liquid sample is introduced into a column of the liquid chromatograph, and a target component contained in the liquid sample is separated from other components by the column, and only the target component is fractionated into a fractionation container. When the target component is fractionated from the sample, the liquid sample is usually injected into a mobile phase with a high flow rate, and then introduced into a short column, and the target component is fractionated in a short time.
[0003] The fractionation liquid chromatograph is used to fractionate target components with efficacy, such as in the development of new drugs in the pharmaceutical field. When confirming the efficacy of the target component, a detailed analysis is performed to confirm that the target component is correct and that there are no impurities mixed in the target component. In this case, after the target component is fractionated into the fractionation container, the detailed analysis conditions of this target component are set and this target component is analyzed. In the detailed analysis of the target component, the analysis conditions are set to improve the separation between components by reducing the flow rate of the mobile phase compared to the fractionation of this target component or using a column longer than the fractionation time, spending more time than the fractionation time.
[0004] [Prior art literature]
[0005] [Patent Document]
[0006] [Patent Document 1] International Patent Publication No. 2018 / 163276 Summary of the invention
[0007] [Problems to be solved by the invention]
[0008] In the previous method, after setting the conditions for extracting the target component in the sample to extract the target component, when performing a detailed analysis on it, the user must confirm the information of the extraction container into which the target component was extracted on the extraction result screen, and then set the detailed analysis conditions of the target component to analyze the target component. The extraction and analysis of the target component takes time.
[0009] Here, the case where the target component is fractionated and analyzed using a liquid chromatograph is described, but the same problem as described above also exists when a chromatographic apparatus such as a gas chromatograph is used.
[0010] The problem to be solved by the present invention is to reduce the man-hours required for fractionating a target component in a sample using a chromatographic device and further analyzing the fractionated target component.
[0011] [Technical means to solve the problem]
[0012] The chromatographic device of the present invention, which is provided to solve the above-mentioned problems, comprises:
[0013] The aliquoting device is provided with a sample container and an aliquoting container, wherein the sample container contains a sample containing a target component, and the aliquoting container contains the aliquoted target component;
[0014] A fractionation analysis condition setting unit for the user to set the fractionation conditions of the target component and the analysis conditions of the target component after fractionation;
[0015] an aliquot execution unit that, after the aliquot condition and the analysis condition are set in the aliquot analysis condition setting unit, collects a sample from the sample container and aliquots the target component contained in the sample into the aliquot container according to the aliquot condition; and
[0016] The analysis execution unit collects the target component from the aliquot container after the aliquot execution section extracts the target component, and analyzes the target component according to the analysis condition.
[0017] [Effects of the Invention]
[0018] In the chromatographic device of the present invention, first, the fractionation and analysis condition setting unit allows the user to set the fractionation conditions and analysis conditions of the target component, and then the fractionation execution unit and the analysis execution unit successively execute the fractionation of the target component contained in the sample and the analysis of the fractionated target component. Therefore, after the target component in the sample is fractionated, the user does not need to confirm the information of the fractionation container from which the target component is fractionated on the fractionation result screen, etc., which can reduce the man-hours for fractionation and analysis of the target component. BRIEF DESCRIPTION OF THE DRAWINGS
[0019] Figure 1 It is a diagram showing the main part of a fractionating liquid chromatography system as one embodiment of the chromatography apparatus of the present invention.
[0020] Figure 2 This is a flowchart for explaining the flow of fractionating and analyzing a target component contained in a sample using the fractionating liquid chromatography system of the present embodiment.
[0021] Figure 3 This is an example of a fractionation analysis condition setting screen in the fractionation liquid chromatography system of the present embodiment.
[0022] Figure 4 This is an example of a result display screen in the fractionating liquid chromatography system of the present embodiment.
[0023] Figure 5This is a diagram for explaining a method of determining a target for detailed analysis when a target component is fractionated into a plurality of vials in the fractionating liquid chromatography system of the present embodiment.
[0024] [Explanation of Symbols]
[0025] 1: Liquid chromatography system
[0026] 10: Liquid chromatography
[0027] 11: Mobile phase container
[0028] 12: Liquid delivery pump
[0029] 13: Injector
[0030] 14: Extraction of tubing string
[0031] 15: First detector
[0032] 16: Second detector
[0033] 17: Liquid Handler
[0034] 171: Board
[0035] 172: Vial containing sample
[0036] 173: Vial containing target ingredient
[0037] 18: Injection
[0038] 181: Syringe Pump
[0039] 182: Needle
[0040] 19: Separation Department
[0041] 191: Nozzle
[0042] 24: Analytical Column
[0043] 25: The third detector
[0044] 40: Control / Processing Unit
[0045] 41: Storage
[0046] 42: Fractionation analysis condition setting unit
[0047] 43: Extraction Execution Department
[0048] 44: Analysis and Execution Department
[0049] 45: Judgment Department
[0050] 46: Result display unit
[0051] 51: Input
[0052] 52: Display unit
[0053] 70: Fractionation analysis condition setting screen
[0054] 71: Vial display area
[0055] 72: Analysis condition display area
[0056] 721: Plate No. Column
[0057] 722: Vial No. Column
[0058] 723: Method column
[0059] 724: Name column
[0060] 725: Injection volume column
[0061] 726: Automatic refill bar
[0062] 727: Re-injection method column
[0063] 728: Reinjection volume column
[0064] 73: Cancel button
[0065] 74: Decision button
[0066] 80: Results display screen
[0067] 81: Total ion current chromatogram
[0068] 82: Mass Spectrometry
[0069] 83: Judgment result DETAILED DESCRIPTION
[0070] Hereinafter, one embodiment of the chromatography device of the present invention will be described with reference to the drawings. The chromatography device of this embodiment is a fractionation liquid chromatography system having a function of fractionating a target component contained in a sample and further analyzing the fractionated target component in detail.
[0071] Figure 1 The main structure of the fractionating liquid chromatography system 1 of this embodiment is shown. The fractionating liquid chromatography system 1 includes a fractionating liquid chromatograph 10 and a control / processing unit 40 .
[0072] The fractionation liquid chromatograph 10 includes: a mobile phase container 11, a liquid delivery pump 12, an ejector 13, a fractionation column 14, a first detector 15, a second detector 16, a liquid processor 17, an analysis column 24, and a third detector 25. Figure 1In the figure, only one mobile phase container 11 and a liquid delivery pump 12 are schematically shown, but it can also be constructed to include a mobile phase container 11 that respectively accommodates multiple mobile phases, a liquid delivery pump 12 that respectively delivers them, and a mixer that mixes the multiple mobile phases. A port for injecting a sample and a port for injecting an analytical sample are provided in the injector 13. The sample is introduced into the fractionation column 14, and the analytical sample is introduced into the analytical column 24. The first detector 15 is a detector that non-destructively measures the components flowing out of the fractionation column 14, for example, an absorption photometer can be used. The second detector 16 is a detector that uses a method different from the first detector 15 to measure the components flowing out of the fractionation column 14, for example, a mass spectrometer can be used. The third detector 25 is a detector that measures the components flowing out of the analytical column 24, and any detector can be used.
[0073] The liquid processor 17 has both the function of an injector for injecting a sample into a mobile phase and the function of a fractionation reservoir for fractionating a desired portion of the effluent from the fractionation column 14 and storing it in a fractionation container. A plate (sample rack) 171 is provided inside the liquid processor 17, and a sample vial 172 for storing a sample and a fractionation vial 173 for storing a target component to be fractionated are placed on the plate 171. In addition, an injection unit 18 and a fractionation unit 19 are provided in the liquid processor 17. The injection unit 18 includes a needle 182 inserted into the sample vial 172 and a syringe pump 181 for collecting and ejecting the sample through the needle 182. The fractionation unit 19 includes a nozzle 191 inserted into the fractionation vial 173. In the injection unit 18, under the control of the aliquot execution unit 43 or the analysis execution unit 44 described later, the sample or target component contained in the specified sample vial 172 is collected and injected into the injector 13. In the aliquot unit 19, based on the detection of the target component by the first detector 15 and / or the second detector 16, the target component contained in the sample is aliquoted into the aliquot vial 173. The liquid processor 17 is equivalent to the aliquoting device of the present invention. In addition, the sample vial 172 is equivalent to the sample container, and the aliquot vial 173 is equivalent to the aliquot container.
[0074] The control / processing unit 40 includes a storage unit 41. In the storage unit 41, for each of a plurality of known components, information on the conditions for fractionation of the component and the conditions for detailed analysis after fractionation of the component is recorded and stored in a method file. These fractionation conditions and analysis conditions include, for example, the type and flow rate of the mobile phase, the type of the fractionation column 14 and the analysis column 24, information related to the detection signal (reference detection signal) of the component in the first detector 15 (when the first detector 15 is an absorption detector, for example, absorption wavelength or absorbance), information related to the detection signal (reference detection signal) of the component in the second detector 16 (when the second detector 16 is a mass spectrometer, for example, mass-to-charge ratio or intensity of ions), and information related to the detection signal (reference detection signal) of the component in the third detector 25. In the analysis conditions, for example, conditions are set to improve the separation degree by reducing the flow rate of the mobile phase compared to the fractionation of the target component or using an analysis column 24 that is longer than the fractionation column 14.
[0075] The control / processing unit 40 includes: a fractionation analysis condition setting unit 42, a fractionation execution unit 43, an analysis execution unit 44, a determination unit 45, and a result display unit 46 as functional blocks. The entity of the control / processing unit 40 is, for example, a general personal computer, and these functional blocks are materialized by executing a pre-embedded dedicated fractionation analysis program by a processor. In addition, the control / processing unit 40 is connected to: an input unit 51 composed of a keyboard, a mouse, etc., and a display unit 52 composed of a liquid crystal display, etc.
[0076] Next, refer to Figure 2 , the flow chart of the present invention is used to illustrate the process of fractionating and analyzing a target component contained in a sample using the fractionating liquid chromatography system 1 of the present embodiment.
[0077] The user first places the sample vial 172 containing the sample containing the target component and the aliquot vial 173 for containing the aliquoted target component on the plate 171, and sets the plate 171 in the liquid processor 17 (step 1). Then, the information of the sample vial 172 and the aliquot vial 173 is registered. When the liquid processor 17 is provided with a plurality of plates 171, the number of the plate 171 is also registered. In the present embodiment, a plate 171 having 24 holes (vial placing portion, numbered 1 to 24) is used, and a total of three sample vials 172 containing three samples and 21 empty aliquot vials 173 are placed on the plate 171 and set in the liquid processor 17. Here, the sample vials 172 containing the sample are placed at positions numbered 1 to 3, and the empty aliquot vials 173 are placed at positions numbered 4 to 24. The sample vials 172 and the aliquot vials 173 may also be placed on different plates.
[0078] When the user instructs to set the fractionation analysis conditions, the fractionation analysis condition setting unit 42 displays a screen on the display unit 52 for setting the fractionation conditions of the target component contained in the sample and the conditions for detailed analysis of the target component after fractionation.
[0079] Figure 3 7 is an example of a setting screen for fractionation conditions and analysis conditions. The fractionation analysis condition setting screen 70 displays: a vial display area 71, a fractionation analysis condition display area 72, a cancel button 73, and a decision button 74. In the fractionation analysis condition display area 72, there are provided: a plate No. column 721, a vial No. column 722, a method column 723, a name column 724, an injection volume column 725, an automatic re-injection column 726, a re-injection method column 727, and a re-injection volume column 728. Thus, in the present embodiment, the plate No. column 721, the vial No. column 722, the method column 723, the name column 724, the injection volume column 725, the automatic re-injection column 726, the re-injection method column 727, and the re-injection volume column 728 are displayed on the same screen, so that the fractionation conditions and the analysis conditions can be set on the same screen. Thus, the convenience of the user is improved.
[0080] In the vial display area 71, a top view of a plate 171 provided in the liquid handler 17 is displayed. In this example, only one plate 171 is provided, but when the liquid handler 17 is provided with a plurality of plates 171, the plurality of plates 171 may be displayed in a switchable or parallel manner. In the vial display area 71, a sample vial 172 containing a sample and an empty aliquot vial 173 are displayed so as to be identifiable based on information previously registered by the user. Figure 3 In the example of , hatching is added to sample vials 172 numbered 1 to 3 in the vials contained in the 24-well plate 171 to indicate that the sample is contained. Here, hatching is added, but the sample vials 172 containing the sample and the empty aliquot vials 173 can also be distinguished by other display methods such as color display.
[0081] The user selects a sample containing a target component to be fractionated from the sample vials 172 (containing the sample) displayed in the vial display area 71 and displayed with a shadow by mouse operation or the like (step 2). When the user selects the sample vial 172 in the vial display area 71, the number of the plate 171 on which the sample vial 172 is placed and the number (position) of the vial in the plate 171 are automatically input to the plate No. column 721 and the vial No. column 722 of the fractionation analysis condition display area 72, respectively.
[0082] Next, the user reads out the method file from the storage unit 41, and the method file records the extraction conditions for extracting the target component from the sample contained in the selected sample vial 172. When the user reads out the method file, its file name is displayed in the method column 723 of the extraction analysis condition display area 72 (step 3). In addition, by executing the method file, the name of the target component to be extracted is read into the name column 724 of the extraction analysis condition display area 72. In the case of extracting multiple target components using one method, the names of the multiple target components are displayed in the name column 724. The user then enters the injection amount of the sample into the injection amount column 725. Here, the user enters the injection amount, but the injection amount can also be pre-set as the extraction condition recorded in the method file, and its value can be automatically read and entered into the injection amount column 725.
[0083] The user then selects whether to automatically perform detailed analysis of the target component separated from the sample (step 4). This selection is made by clicking the check box set in the automatic re-injection column 726 and entering a check mark.
[0084] When a check mark is input in the automatic re-injection column 726, the fractionation analysis condition setting unit 42 accepts input to the re-injection method column 727. The user reads out the method file recording the conditions for detailed analysis of the target component to be fractionated from the storage unit 41. When the user reads out the method file, its file name is displayed in the re-injection method column 727 of the fractionation analysis condition display area 72. The user then inputs the injection amount when the target component is analyzed in detail into the re-injection amount column 728. Here, the user inputs the injection amount, but the injection amount may be pre-set as the analysis condition recorded in the method file, and its value may be automatically read and input into the re-injection amount column 728.
[0085] When the input is completed for all samples for which the target component is to be fractionated and analyzed in detail, and the user presses the determination button 74, the fractionation analysis condition setting unit 42 reads the sample selected by the user, the fractionation conditions for fractionating the target component from the sample, and the conditions for detailed analysis of the fractionated target component, and creates a file for continuously executing them (step 5). When the user presses the cancel button 73, the fractionation analysis conditions input at this time are reset. The fractionation analysis condition setting unit 42 creates an execution file for only executing the fractionation of the target component for the sample for which no mark is entered in the automatic re-injection column 726, and creates an execution file for executing the fractionation of the target component for the sample for which a mark is entered in the automatic re-injection column 726, and then automatically re-injects the fractionated target component and performs detailed analysis.
[0086] After the fractionation analysis execution file is created, when the user instructs to start fractionation and analysis of the target component through a predetermined input operation, the fractionation execution unit 43 controls each unit of the fractionation liquid chromatograph 10 to collect a sample from the plate 171 and the sample vial 172 initially selected by the user in the fractionation analysis condition display area 72. The target component contained in the sample is separated from other components and flows out while passing through the fractionation column 14. Based on the detection of the flowing target component by the first detector 15 and / or the second detector 16, the fractionation unit 19 fractionates the target component into the fractionation vial 173 (step 6).
[0087] The aliquoting unit 19 aliquots the target component to the empty aliquoting vials 173 in ascending order of number. In the present embodiment, since the sample vials 172 numbered 1 to 3 contain the sample, the target component is aliquoted sequentially from the aliquoting vial 173 numbered 4. The aliquoting amount to be aliquoted to one aliquoting vial 173 is predetermined, and when the sample solution containing the target component exceeds this amount and flows out of the aliquoting column 14, the aliquoting unit 19 switches the aliquoting vial 173 for collecting the target component to the next aliquoting vial 173 numbered 5. When the target component is collected by the aliquoting unit 19, the aliquoting execution unit 43 stores the information (plate number and vial number) of the aliquoting vial 173 for collecting the target component together with the sample name, the target component name, the detection signal of the first detector 15 during collection, and the detection signal of the second detector 16 in the storage unit 41 (step 7).
[0088] When an execution file is created to execute only the extraction of the target component, only the target component contained in the sample is extracted. On the other hand, when an execution file is created to further perform a detailed analysis of the extracted target component after the extraction of the target component is executed, the analysis execution unit 44 controls each unit of the extraction liquid chromatograph 10, and executes a detailed analysis of the extracted target component using the analysis column 24 and the third detector 25 based on the conditions described in the execution file (step 8).
[0089] When the fractionation and detailed analysis of the target component are completed for the first sample (when the detailed analysis is set to be performed), the fractionation execution unit 43 determines whether there is an unprocessed sample (step 9). If there is an unprocessed sample (yes in step 9), the process returns to step 5 and the fractionation and detailed analysis of the target component are performed on the unprocessed sample. If the processing of all samples is completed and there is no unprocessed sample (no in step 9), the operations related to the fractionation and detailed analysis of the target component are terminated.
[0090] When the target components of all samples are separated and analyzed in detail, the determination unit 45 determines the results of the detailed analysis for the target components that have been analyzed in detail. Specifically, for example, the detection signal (such as an absorption spectrum or a mass spectrum) of the third detector 25 obtained in the detailed analysis of the target component is compared with the reference detection signal (such as an absorption spectrum or a mass spectrum) of the target component stored in the storage unit 41, and it is determined whether the two are consistent within a predetermined allowable range (step 10). In the case where it is determined that the two are consistent, the determination unit 45 determines that the fraction is the target component and no impurities are mixed. In the case where it is determined that the two are inconsistent, it is further determined whether the detection signal (such as an absorption spectrum or a mass spectrum) of the third detector 25 obtained during the detailed analysis includes the detection signal (such as an absorption spectrum or a mass spectrum) of the target component stored in the storage unit 41. Then, in the case of including the detection signal of the target component stored in the storage unit 41, it is determined that the fraction contains the target component and impurities, and in the case of not including the detection signal of the target component, it is determined that the fraction is not the target component. Specifically, for example, when a mass peak in the standard mass spectrum and a mass peak not present in the standard mass spectrum appear in the mass spectrum created from the detection signal of the third detector 25 , it is determined that the target component and impurities are contained in the fraction.
[0091] When the determination unit 45 completes the determination of all target components that have been subjected to detailed analysis, the result display unit 46 displays the fractionation / analysis results on the screen of the display unit 52, and the fractionation / analysis results include: the detection signals obtained by the first detector 15 and the second detector 16 when the target components are fractionated from each sample, the detection signals obtained by the third detector 25 when the fractionated target components are subjected to detailed analysis, and the determination results determined by the determination unit 45 (step 11).
[0092] Figure 4An example of the result display screen 80 displayed by the result display unit 46 is shown. The example of this result display screen 80 is an example of fractionation and detailed analysis of the target component A and the target component B contained in the sample. On the result display screen 80, the total ion current (Total Ions Current Chromatogram, TICC) chromatogram 81 obtained when the target component A and the target component B are fractionated, the mass spectrum 82 obtained when the fractions respectively separated at the positions corresponding to the peaks on the TICC chromatogram 81 are analyzed in detail, and the determination results 83 related to each fraction are displayed. The number of the fraction vial 173 containing the fraction is also displayed in the mass spectrum 82. In each mass spectrum 82, when the determination unit 45 makes a determination, the mass peak (i.e., the mass peak of the target component) whose mass-to-charge ratio is determined to be consistent with the mass peak of the standard mass spectrum is indicated by a solid line, and the mass peak (i.e., the mass peak of the impurity) determined to be inconsistent is indicated by a dotted line. Then, under each mass spectrum 82, the determination result determined by the determination unit 45 is displayed. By checking the result display screen 80 , the user can visually recognize whether the separated object is the target component and whether the target component contains impurities.
[0093] In the past, after setting the conditions for aliquoting a target component in a sample and aliquoting the target component, when performing a detailed analysis on the aliquot result screen, the user had to confirm the information of the aliquot container into which the target component was aliquoted, and then set the detailed analysis conditions for the target component to analyze the target component, which took a lot of time to aliquot and analyze the target component.
[0094] In the fractionation liquid chromatography system 1 of the present embodiment, first, the fractionation analysis condition setting unit 42 allows the user to set the fractionation conditions and analysis conditions of the target component, and then the fractionation execution unit 43 and the analysis execution unit 44 successively execute the fractionation of the target component contained in the sample and the analysis of the fractionated target component. Therefore, after the target component in the sample is fractionated, the user does not need to confirm the information of the fractionation container from which the target component is fractionated on the fractionation result screen, etc., which can reduce the time for fractionation and analysis of the target component.
[0095] As described above, the collection amount of one aliquot vial 173 is predetermined, and when the amount of the sample solution containing the target component exceeds the collection amount, the target component is collected in a plurality of aliquot vials 173. Although all of the plurality of aliquot vials 173 collected in this way can be analyzed in detail, since the aliquots aliquoted into the plurality of aliquot vials 173 are substantially the same, the efficiency of the analysis is better when only the target component aliquoted into any one aliquot vial 173 is analyzed in detail.
[0096] The following describes a process for determining the aliquot vial 173 to be analyzed in detail when the sample liquid that flows out from the aliquot column 14 continuously in time is aliquoted into a plurality of aliquot vials 173. Figure 5 The following describes a case where the second detector 16 is a mass spectrometer and the aliquot vial 173 for executing detailed analysis is determined based on mass spectrum data acquired by the mass spectrometer. Figure 5 This is a case where the sample liquid that flows out from the fractionation column 14 continuously in terms of time is fractionated into three fractionation vials 173 (numbers 11 to 13).
[0097] In the time band where the sample liquid continuously flowing out at the time is aliquoted into a plurality of aliquot vials 173, the analysis execution unit 44 reads the mass spectrum data obtained by repeatedly performing mass spectrometry (MS) scanning measurement by the second detector 16. Then, based on the plurality of mass spectrum data obtained in the time band where the target component is aliquoted into each aliquot vial 173, the average mass spectrum ( Figure 5 Here, MS scanning measurement is performed to obtain a mass spectrum, but instead, three selective ion monitoring (SIM) measurements of target ions from target component A, target ions from target component B, and non-target ions may be repeatedly performed. Alternatively, when the time (retention time) at which target component A and target component B flow out of the fractionation column 14 is known, SIM measurement of target ions and non-target ions of target component A may be performed at the retention time of target component A, and SIM measurement of target ions and non-target ions of target component B may be performed at the retention time of target component B.
[0098] Next, the analysis execution unit 44 calculates, for each of the three fractionation vials 173 (numbers 11 to 13), the intensity of the mass peak in the mass-charge ratio of the target ion, which is a representative ion from the target component, and the intensity of the mass peak in the mass-charge ratio of the non-target ion, which is from components other than the target component and is measured with the same intensity regardless of the time band. The values of the mass-charge ratio of the target ion are pre-stored in the storage unit 41 for each target component, and the values of the mass-charge ratio of the non-target ion are pre-stored for each fractionation condition. The mass-charge ratio of the non-target ion can be set, for example, to the mass-charge ratio of the ion generated by the mobile phase flowing into the detector regardless of time. In Figure 5 In the example of , the mass-to-charge ratio of the target ion is 505, and the mass-to-charge ratio of the non-target ion is 256. The intensity of the mass peak is obtained from the area value or height of the mass peak.
[0099] Then, the analysis execution unit 44 calculates the ratio of the intensity of the mass peak of the target ion to the intensity of the mass peak of the non-target ion for each of the three fraction vials 173 (numbers 11 to 13). Then, the vial 173 with the largest ratio is determined as a candidate for collecting the target component during the detailed analysis, and the sample of the candidate fraction vial 173 is used as the object, and the detailed analysis is performed using the re-injection method and re-injection amount preset before the start of fractionation. In this example, the fraction vial 173 numbered 12 becomes a candidate for collecting the target component during the detailed analysis.
[0100] In addition, the analysis execution unit 44 determines whether the intensity of the mass peak of the target ion associated with the candidate vial exceeds a predetermined threshold value. This threshold value may be preset as one of the analysis conditions and stored in the storage unit 41. And, if the intensity of the mass peak of the target ion associated with the candidate vial exceeds the threshold value, the candidate vial is finally determined as an object for collecting the target component in the detailed analysis.
[0101] As described above, by determining the vial from which the target component is collected during the detailed analysis, it is not necessary to separately perform detailed analysis on multiple vials from which the same target component is separated, thereby improving the efficiency of the detailed analysis. In addition, at this time, by selecting the vial with the highest ratio of the intensity of the mass peak of the target ion to the intensity of the mass peak of the non-target ion, the target component can be collected from the vial from which more target components are separated for detailed analysis. In addition, by only taking the vial from which the intensity of the mass peak of the target ion exceeds the threshold as the object of detailed analysis, the consumption of the target component separated in a small amount can be suppressed. For the target component separated in a small amount, the detailed analysis can be performed using other methods that can be performed in a small amount.
[0102] The above embodiment is an example and can be changed appropriately according to the main idea of the present invention. In the above embodiment, when the same target component is aliquoted into multiple vials, the target ion mass peak intensity exceeds the threshold value and is used as the object of detailed analysis. However, when the target component is aliquoted into only one vial, the target ion mass peak intensity exceeds the threshold value and is used as the condition for detailed analysis. In this way, the consumption of aliquoting only a small amount of the target component can be suppressed.
[0103] In the above embodiment, the ratio of the intensity of the mass peak of the target ion to the intensity of the mass peak of the non-target ion is calculated, and the vial with the largest ratio is determined as a candidate for collecting the target component in the detailed analysis. However, if there are no ions suitable as non-target ions, the vial with the largest intensity of the mass peak of the target ion may be used as a candidate for collecting the target component in the detailed analysis. In addition, in the above embodiment, as an example, the mass peak appearing in the mass spectrum is used, but when determining the candidate for collecting the target component in the detailed analysis, the detection signal corresponding to the type of detector may be used.
[0104] The above embodiment is a fractionation liquid chromatography system 1, but the same structure can be adopted even in a system including a gas chromatograph instead of a liquid chromatograph.
[0105] [Example]
[0106] It is clear to those skilled in the art that the above-described exemplary embodiments are specific examples of the following embodiments.
[0107] (Item 1)
[0108] A chromatographic device according to an embodiment of the present invention comprises:
[0109] The aliquoting device is provided with a sample container and an aliquoting container, wherein the sample container contains a sample containing a target component, and the aliquoting container contains the aliquoted target component;
[0110] A fractionation analysis condition setting unit for the user to set the fractionation conditions of the target component and the analysis conditions of the target component after fractionation;
[0111] an aliquot execution unit that, after the aliquot condition and the analysis condition are set in the aliquot analysis condition setting unit, collects a sample from the sample container and aliquots the target component contained in the sample into the aliquot container according to the aliquot condition; and
[0112] The analysis execution unit collects the target component from the aliquot container after the aliquot execution section extracts the target component, and analyzes the target component according to the analysis condition.
[0113] In the chromatographic device of item 1, first, the fractionation and analysis condition setting section allows the user to set the fractionation conditions and analysis conditions of the target component, and then the fractionation execution section and the analysis execution section successively execute the fractionation of the target component contained in the sample and the analysis of the target component after the fractionation. Therefore, after the target component in the sample is fractionated, the user does not need to confirm the information of the fractionation container from which the target component is fractionated on the fractionation result screen, etc., and the man-hours for fractionation and analysis of the target component can be reduced.
[0114] (Item 2)
[0115] The chromatographic device of item 2 is a chromatographic device according to item 1, wherein
[0116] The fractionation and analysis condition setting unit further allows the user to set whether to perform analysis of the target component after the fractionation of the target component.
[0117] The analysis execution unit executes the analysis of the target component after the target component is fractionated, when the user sets to execute the analysis of the target component.
[0118] In the chromatography device of item 2, detailed analysis can be selectively performed only on target components that the user deems necessary for detailed analysis.
[0119] (Item 3)
[0120] The chromatographic device of item 3 is a chromatographic device according to item 1 or 2, wherein
[0121] The analysis execution unit executes analysis of the target component based on the fact that a detection signal obtained when the target component is extracted satisfies a predetermined criterion.
[0122] The predetermined criterion may be, for example, that the size of the detection signal obtained when the target component is fractionated exceeds a predetermined threshold value. In the chromatographic device of item 3, only when a sufficient amount of the target component satisfying the predetermined criterion is fractionated, the target component is subjected to detailed analysis, thereby suppressing the consumption of the target component caused by detailed analysis when the fractionated amount of the target component is small.
[0123] (Item 4)
[0124] The chromatographic device of item 4 is a chromatographic device according to any one of items 1 to 3, wherein
[0125] When the aliquot execution unit collects the target component into a plurality of aliquot containers in a temporally continuous manner, the analysis execution unit performs analysis on only the target component contained in any one of the plurality of aliquot containers.
[0126] Since the amount that can be dispensed in one aliquoting container is predetermined, when the amount of the target component is larger than the amount, the same target component is dispensed to a plurality of aliquoting containers in a temporally continuous manner. In the chromatographic apparatus of item 4, since the aliquoting container from which the most target component is dispensed is determined from such a plurality of aliquoting containers, only the target component dispensed to this aliquoting container is analyzed in detail, thus the efficiency of analysis is improved compared to analyzing in detail all of the same target component dispensed to a plurality of aliquoting containers.
[0127] (Item 5)
[0128] The chromatographic device of item 5 is a chromatographic device according to item 4, wherein
[0129] The analysis execution unit executes analysis only on the target component contained in one aliquot container having the largest detection signal of the target component obtained during aliquoting of the target component into the plurality of aliquot containers.
[0130] In the chromatography apparatus of item 5, since the target component is collected from the fractionation container from which the largest amount of the target component is fractionated among the plurality of fractionation containers and detailed analysis is performed, detailed analysis can be performed more accurately.
[0131] (Item 6)
[0132] The chromatographic device of item 6 is a chromatographic device according to item 5, wherein
[0133] The detection signal is the intensity obtained by measuring the ions generated by the target component using a mass spectrometer. Compared with the intensity obtained by measuring the ions generated by components other than the target component and having no correlation in a time band using a mass spectrometer, the analysis execution unit only performs analysis on the target component contained in a predetermined fractionation container in which the measured intensity of the ions generated by the target component is the largest.
[0134] In the chromatographic apparatus of item 6, since the measurement signal obtained by the mass spectrometer having high compound recognition capability is used, the fractionation container from which the largest amount of the target component has been fractionated can be identified with high accuracy.
[0135] (Item 7)
[0136] The chromatographic device of item 7 is a chromatographic device according to any one of items 1 to 6, wherein
[0137] The fractionation conditions and the analysis conditions can be set on the same screen.
[0138] In the chromatographic apparatus of item 7, since the fractionation conditions and the analysis conditions can be set on the same screen, the convenience for the user is improved.
Claims
1. A chromatographic device, characterized in that include: The aliquoting device is provided with a sample container and an aliquoting container, wherein the sample container contains a sample containing a target component, and the aliquoting container contains the aliquoted target component; A fractionation analysis condition setting unit for the user to set the fractionation conditions of the target component and the analysis conditions of the target component after fractionation; an aliquot execution unit, which, after the aliquot condition and the analysis condition are set in the aliquot analysis condition setting unit, collects a sample from the sample container and aliquots the target component contained in the sample into the aliquot container according to the aliquot condition; as well as The analysis execution unit collects the target component from the aliquot container after the aliquot execution section extracts the target component, and analyzes the target component according to the analysis condition.
2. The chromatographic device according to claim 1, characterized in that The fractionation and analysis condition setting unit further allows the user to set whether to perform analysis of the target component after the fractionation of the target component. The analysis execution unit executes the analysis of the target component after the target component is fractionated, when the user sets to execute the analysis of the target component.
3. The chromatographic device according to claim 1, characterized in that The analysis execution unit executes analysis of the target component based on the fact that a detection signal obtained when the target component is fractionated satisfies a predetermined criterion.
4. The chromatographic device according to claim 1, characterized in that When the aliquot execution unit collects the target component into a plurality of aliquot containers in a temporally continuous manner, the analysis execution unit performs analysis on only the target component contained in any one of the plurality of aliquot containers.
5. The chromatographic device according to claim 4, characterized in that The analysis execution unit executes analysis only on the target component contained in one aliquot container having the largest detection signal of the target component obtained during aliquoting of the target component into the plurality of aliquot containers.
6. The chromatographic device according to claim 5, characterized in that The detection signal is the intensity of ions generated from the target component measured by a mass spectrometer. The analysis execution unit performs analysis only on the target component contained in a predetermined fractionation container having the largest measured intensity of ions generated by components other than the target component, relative to the intensity measured by a mass spectrometer on ions generated independently in a time band from components other than the target component.
7. The chromatographic device according to claim 1, characterized in that The fractionation conditions and the analysis conditions can be set on the same screen.
Citation Information
Patent Citations
Fraction collector control device and preparative liquid chromatograph
WO2018163276A1