Chromatographic analysis device

Abstract

A chromatography analysis device is provided with: a system information storage unit (2) for storing a system capacity, which is the capacity of a pipe through which a sample of a fluid chromatograph (100) passes; an analysis information storage unit (4) that stores a chromatogram obtained by the analysis performed by the fluid chromatograph, flow rate information relating to the flow rate of the mobile phase at the time of analysis, and composition information relating to the composition of the mobile phase at each time period at the time of analysis; a time calculation unit (6) that calculates, on the basis of the system capacity, the flow rate information, and the composition information, a mobile phase arrival time required for a mobile phase delivered from a liquid delivery device (102) of the fluid chromatograph to reach a detector (108), and a sample arrival time required for a sample into which the mobile phase is injected to reach the detector; a target range determination unit (8) that determines a target range for peak analysis on the chromatogram on the basis of the mobile phase arrival time and the sample arrival time so as to exclude composition-caused peaks and injection-caused peaks from analysis targets; and a peak analysis unit (10) that performs peak analysis in the target range determined by the target range determination unit.

Description

Technical Field

[0001] This invention relates to a chromatographic analysis apparatus. Background Technology

[0002] There is a device for performing chromatographic analysis, wherein the chromatogram is obtained by a fluid chromatograph such as a liquid chromatograph or a supercritical fluid chromatograph (see Patent Document 1). The chromatographic analysis device can not only detect the peaks appearing in the chromatogram to determine the area of ​​each peak, but also separate multiple overlapping peaks to infer the shape and size of each peak.

[0003] Existing technical documents

[0004] Patent documents

[0005] Patent Document 1: Japanese Patent Application Publication No. 2021-148776 Summary of the Invention

[0006] The technical problem that the invention aims to solve

[0007] In liquid chromatography and supercritical fluid chromatography, abrupt changes in the composition of the mobile phase and rapid pressure changes caused by sample injection are sometimes recorded as peaks on the chromatogram. However, if such noise peaks are identified by the analytical apparatus as peaks originating from components in the sample, the reliability of the analytical results is compromised. For example, when the amount of components contained in the sample is known, the number of peaks to be analyzed is sometimes preset. However, if a noise peak is identified as a component peak, the component peak that should have been analyzed is missed, resulting in a situation where analysis is not performed. Therefore, before performing analytical processing, users need to remove noise peaks that are not originating from components. However, this operation is cumbersome and it is difficult to distinguish between peaks originating from components and noise peaks.

[0008] The present invention was made in view of the above-mentioned problems, and its object is to provide a chromatographic analysis apparatus having the function of automatically eliminating noise peaks from the analysis object.

[0009] Solution to the above technical problems

[0010] The chromatographic analysis apparatus involved in this invention comprises:

[0011] The system information storage unit stores the capacity of the pipe through which the sample from the fluid chromatograph passes, which is the system capacity.

[0012] The analysis information storage unit stores the chromatogram obtained by the analysis performed by the fluid chromatograph, the flow rate information related to the flow rate of the mobile phase during the analysis, and the composition information related to the composition of the mobile phase in each time period during the analysis.

[0013] The time calculation unit is configured to calculate the mobile phase arrival time and the sample arrival time based on the system capacity, the flow rate information and the composition information. The mobile phase arrival time is the time required for the mobile phase delivered from the liquid delivery device of the fluid chromatograph to reach the detector, and the sample arrival time is the time required for the sample injected with the mobile phase to reach the detector.

[0014] The target range determination unit is configured to determine the target range of peak analysis on the chromatogram based on the arrival time of the mobile phase and the arrival time of the sample, so as to exclude composition-caused peaks and injection-caused peaks from the analysis target. The composition-caused peaks are peaks caused by abrupt changes in the composition of the mobile phase, and the injection-caused peaks are peaks caused by the injection of the sample into the mobile phase.

[0015] The peak resolution unit is configured to perform peak resolution within the object range determined by the object range determination unit.

[0016] Invention Effects

[0017] According to the chromatographic analysis apparatus of the present invention, based on the system capacity of the fluid chromatograph, the flow rate information of the mobile phase, and the composition information related to the composition of the mobile phase in each time period, the arrival time of the mobile phase and the arrival time of the sample are calculated. Based on the calculated arrival time of the mobile phase and the arrival time of the sample, the range of analysis objects is determined to exclude compositional peaks and injection-induced peaks that are noise peaks from the analysis objects. Peak analysis is performed within the determined range of analysis objects, thus enabling the automatic exclusion of noise peaks from the analysis objects. Attached Figure Description

[0018] Figure 1 This is a schematic diagram illustrating an embodiment of a chromatographic analysis apparatus.

[0019] Figure 2 The figure above is an example of the steps for determining the scope of the analysis in this embodiment. The upper figure is a chromatogram obtained from the analysis of a sample, and the lower figure is a graph showing the composition (concentration of liquid B) of the mobile phase at different time points during the analysis.

[0020] Figure 3 This is a flowchart illustrating one example of the operation of this embodiment. Detailed Implementation

[0021] Hereinafter, an embodiment of the chromatographic analysis apparatus will be described with reference to the accompanying drawings.

[0022] like Figure 1 As shown, the chromatographic analysis apparatus 1 is an apparatus for analyzing the chromatogram obtained by analyzing a sample using a fluid chromatograph 100, and is implemented by a computer device (e.g., a personal computer) equipped with an analysis program.

[0023] The fluid chromatograph 100 is a liquid chromatograph, comprising a delivery device 102, an autosampler 104, a separation column 106, a detector 108, and a controller 110. The delivery device 102 separately delivers liquids A and B into a mixer for mixing, and delivers the mixture as the mobile phase. The autosampler 104 is fluidly connected downstream of the delivery device 102, injecting the sample into the mobile phase delivered from the delivery device 102. The separation column 106 is fluidly connected downstream of the autosampler 104, separating multiple components of the sample injected into the mobile phase by the autosampler 104. The detector 108 is fluidly connected downstream of the separation column 106, outputting a signal with an intensity corresponding to the concentration of each component separated by the separation column 106. The controller 110 controls at least the operation of the delivery device 102 and the autosampler 104. The signal output from the detector 108 is input to the chromatographic analysis apparatus 1 via the controller 110.

[0024] Additionally, the fluid chromatograph 100 used to obtain the sample is a liquid chromatograph, but it can also be a supercritical fluid chromatograph or an ion chromatograph.

[0025] The chromatographic analysis apparatus 1 includes a system information storage unit 2, an analytical information storage unit 4, a time calculation unit 6, a target range determination unit 8, and a peak analysis unit 10. The system information storage unit 2 and the analytical information storage unit 4 are implemented using a portion of the storage area of ​​an information storage device such as a hard disk drive or flash memory. The time calculation unit 6, the target range determination unit 8, and the peak analysis unit 10 are implemented by a CPU (central processing unit) executing a predetermined program.

[0026] The system information storage unit 2 stores system information including the system capacity of the fluid chromatograph 100. The system capacity can include the capacity from the mixer of the delivery device 102 to the autosampler 104, the capacity of the flow path within the autosampler 104, the capacity from the autosampler 104 to the separation column 106, the capacity within the separation column 106, and the capacity from the separation column 106 to the detector 108.

[0027] The analysis information storage unit 4 stores the chromatogram obtained by the analysis performed by the fluid chromatograph 100, the flow rate information of the mobile phase during the analysis, and the composition information of the mobile phase at each time point during the analysis (e.g., gradient program).

[0028] The time calculation unit 6 is configured to use system information stored in the system information storage unit 2, flow information and composition information stored in the analysis information storage unit to calculate the sample arrival time T1 and the mobile phase arrival time T2. The sample arrival time T1 is the time required for the sample to reach the detector 108 before being captured by the separation column 106, and the mobile phase arrival time T2 is the time required for the mobile phase delivered from the liquid delivery device 102 to reach the detector 108.

[0029] The sample arrival time T1 can be determined by dividing the internal volume from the autosampler 104 to the detector 108 by the flow rate of the mobile phase. Furthermore, the mobile phase arrival time T2 can be determined by dividing the internal volume from the delivery device 102 to the detector 108 by the flow rate of the mobile phase.

[0030] The target range determination unit 8 is configured to determine the target range on the chromatogram based on the sample arrival time T1 and the mobile phase arrival time T2 calculated by the time calculation unit 6. The target range is determined in such a way that the target does not contain injection-caused peaks and composition-caused peaks, where the injection-caused peaks are peaks that may appear due to the injection of the sample and the composition-caused peaks are peaks that may appear due to abrupt changes in the composition of the mobile phase.

[0031] The peak resolution unit 10 is configured to perform chromatographic peak resolution within the resolution target range determined by the target range determination unit 8.

[0032] use Figure 2 The steps for determining the scope of the parsed object are explained.

[0033] If the time when the solvent injected along with the sample arrives at the detector, i.e., the time of sample injection, is set as t0, then the injection-cause peak caused by the sample injection can appear near t0+T1, which is t0 plus the time T1 after the sample arrival. However, if... Figure 2 As shown, injection-induced peaks sometimes have a negative intensity portion in the first half of the peak. Therefore, when a peak appears near time t0+T1, it can be determined whether it is an injection-induced peak based on whether the peak has a negative intensity portion. If a peak with a negative intensity portion appears near time t0+T1 on the chromatogram, the start time of the analytical target range can be set to t0+T1+α to exclude that peak from the analytical target. α is a value set to account for sufficient margin, ensuring that the analytical target does not contain injection-induced peaks.

[0034] On the other hand, if a peak appears near the chromatographic time t0+T1, but the peak does not have a negative intensity portion, it can be considered that the peak originates from a component that the separation column 106 does not have holding power for (dissolving out of the separation column 106 along with the solvent). Therefore, the range of the analytical target is set in such a way that this peak is included in the analytical target. In this case, for example, the starting point of the analytical target range can be set as t0+T1-α.

[0035] Furthermore, if the moment when the composition of the mobile phase delivered by the delivery device 102 undergoes a sharp change is set as t1, then a compositional origin peak caused by the sharp change in the composition of the mobile phase can be observed near the time t1+T2, which is the time required for the mobile phase with the sharp change in composition to reach the detector 108 from the delivery device 102. Therefore, the end time of the analysis target range can be set to t1+T2-β to exclude the compositional origin peak from the analysis target. β is a value set to account for sufficient margin so that the analysis target does not contain a compositional origin peak. β can be the same as or different from α.

[0036] In addition, the timing of a rapid change in the composition of the mobile phase, such as Figure 2 As illustrated in the examples, besides the timing of gradually increasing the concentration of solution B in the mobile phase after injecting the sample and starting the analysis, and restoring the concentration of solution B to the equilibrium concentration (0%) after a certain period of time after the concentration of solution B reaches 100% (after the gradient delivery is completed), other examples include gradually increasing the concentration of solution B in the mobile phase, gradually increasing the concentration of solution B to the final concentration (e.g., 80%) in a gradient manner, and then increasing the concentration of solution B to the washing concentration (100%). The timing of a sharp change in the composition of the mobile phase can be determined, for example, based on the gradient program set for each analysis.

[0037] Next, use Figure 1 as well as Figure 3 The flowchart illustrates the peak analysis steps of the chromatographic analysis apparatus 1.

[0038] If the user selects the chromatogram for which peak analysis is to be performed and enters an instruction to start analysis, the time calculation unit 6 calculates the sample arrival time and the mobile phase arrival time based on the information stored in the system information storage unit 2 and the analysis information storage unit 4, respectively (step 101).

[0039] Next, the target range determination unit 8 uses the sample arrival time and mobile phase arrival time calculated by the time calculation unit 6 to determine the target range for analysis by excluding injection cause peaks and composition cause peaks from the target of analysis (step 102).

[0040] If the range of objects to be analyzed is determined, the peak analysis unit 10 performs peak analysis within the determined range of objects to be analyzed (step 103). The chromatographic analysis apparatus 1 outputs the analysis data obtained by the peak analysis performed by the peak analysis unit 10 to the display 12 and displays it.

[0041] Furthermore, the above embodiments are merely one example of the implementation of the chromatographic analysis apparatus according to the present invention. The implementation of the chromatographic analysis apparatus according to the present invention is as follows.

[0042] One embodiment of the chromatographic analysis apparatus according to the present invention comprises:

[0043] The system information storage unit stores the capacity of the pipe through which the sample from the fluid chromatograph passes, which is the system capacity.

[0044] The analysis information storage unit stores the chromatogram obtained by the analysis performed by the fluid chromatograph, the flow rate information related to the flow rate of the mobile phase during the analysis, and the composition information related to the composition of the mobile phase in each time period during the analysis.

[0045] The time calculation unit is configured to calculate the mobile phase arrival time and the sample arrival time based on the system capacity, the flow rate information and the composition information. The mobile phase arrival time is the time required for the mobile phase delivered from the liquid delivery device of the fluid chromatograph to reach the detector, and the sample arrival time is the time required for the sample injected with the mobile phase to reach the detector.

[0046] The target range determination unit is configured to determine the target range of peak analysis on the chromatogram based on the arrival time of the mobile phase and the arrival time of the sample, so as to exclude composition-caused peaks and injection-caused peaks from the analysis target. The composition-caused peaks are peaks caused by abrupt changes in the composition of the mobile phase, and the injection-caused peaks are peaks caused by the injection of the sample into the mobile phase.

[0047] The peak resolution unit is configured to perform peak resolution within the object range determined by the object range determination unit.

[0048] In the first embodiment described above, the target range determination unit is configured such that, in the case where a peak with a negative intensity portion appears at a position near the time when the sample arrives, which is a certain time elapsed since the sample was injected into the mobile phase, the start time of the target range is defined as a time when a certain amount of time has elapsed since the sample arrives, compared to the time when the sample arrives.

[0049] In the first embodiment described above, the target range determination unit can be configured such that, in the case where a peak without a negative intensity portion appears at a position near the time when the sample arrives, which is a certain time earlier than the time when the sample arrives, the start time of the target range is set as the time when the target range begins.

[0050] In the second embodiment described above, the target range determination unit is configured to define the end time of the target range as a time that is a certain time earlier than the time when the mobile phase arrival time has elapsed since the moment when the composition of the mobile phase changes drastically. This second embodiment can be combined with the first embodiment described above.

[0051] In the third embodiment described above, the composition information is a pre-set gradient program for the mobile phase. This third embodiment can be combined with the first and / or second embodiments described above.

[0052] In the fourth embodiment described above, the system capacity includes the first system capacity, which is the capacity from the autosampler injecting the sample to the detector, and the second system capacity, which is the capacity from the liquid delivery device for delivering the mobile phase to the detector. This fourth embodiment can be combined with the first, second, and / or third embodiments described above.

[0053] Explanation of reference numerals in the attached figures

[0054] 1. Chromatographic analysis apparatus

[0055] 2 System Information Storage Department

[0056] 4. Analysis Information Storage Department

[0057] 6. Time Calculation Department

[0058] 8. Scope of the Object Determination Department

[0059] 10-peak analysis section

[0060] 12 monitors

[0061] 100 fluid chromatograph

[0062] 102 liquid delivery device

[0063] 104 Automatic Sampler

[0064] 106 Separation Column

[0065] 108 detectors

[0066] 110 controller.

Claims

1. A chromatographic resolution device, characterized by, Possessing: a system information storage section that stores a volume of a pipe through which a sample of a fluid chromatograph passes, that is, a system volume; an analysis information storage section that stores a chromatogram acquired through analysis performed by the fluid chromatograph, flow rate information related to a flow rate of the mobile phase at the time of the analysis, and composition information related to a composition of the mobile phase in each time period at the time of the analysis; a time calculation section configured to calculate a mobile phase arrival time or a sample arrival time based on the system volume, the flow rate information, and the composition information, the mobile phase arrival time being a time required for a mobile phase discharged from a liquid delivery device of the fluid chromatograph to reach a detector, the sample arrival time being a time required for a sample injected into the mobile phase to reach the detector from an autosampler of the fluid chromatograph; an object range determination section configured to determine an object range for peak analysis on the chromatogram based on the mobile phase arrival time or the sample arrival time; a peak analysis section configured to perform the peak analysis in the object range determined by the object range determination section.

2. The chromatographic resolving apparatus of claim 1 wherein, The object range determination section is configured to, in a case where a peak having a negative intensity portion appears in the chromatogram at a position near a time at which the sample arrival time elapses from a time at which a sample is injected into the mobile phase, set a time at which a certain time elapses from the time at which the sample arrival time elapses from the time at which the sample is injected into the mobile phase as a start time of the object range.

3. The chromatographic resolving apparatus of claim 2 wherein, The object range determination section is configured to, in a case where a peak not having a negative intensity portion appears in the chromatogram at a position near a time at which the sample arrival time elapses from a time at which a sample is injected into the mobile phase, set a time at which a certain time elapses in advance from the time at which the sample arrival time elapses from the time at which the sample is injected into the mobile phase as a start time of the object range.

4. The chromatographic resolving apparatus of claim 1 wherein, The object range determination section is configured to, at a time after a gradient liquid delivery of the mobile phase in the chromatogram ends, set a time at which a certain time elapses in advance from a time at which a composition of the mobile phase discharged from the liquid delivery device sharply changes as an end time of the object range.

5. The chromatographic resolving apparatus of claim 4 wherein, The object range determination section is configured to, at a time at which the composition of the mobile phase discharged from the liquid delivery device recovers to an equilibration concentration from a gradient final concentration or a time at which a cleaning concentration is set, set a time at which a certain time elapses in advance from a time at which the mobile phase arrival time elapses as the end time.

6. The chromatographic resolving apparatus of claim 1 wherein, The composition information is a gradient program of the mobile phase that is set in advance.

7. The chromatographic resolving apparatus of claim 1 wherein, The system volume includes a volume from an autosampler that injects a sample to a detector, that is, a first system volume, and a volume from a liquid delivery device that delivers a mobile phase to the detector, that is, a second system volume.

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