WO2012004847A1

WO2012004847A1 - Chromatogram display processing device

Info

Publication number: WO2012004847A1
Application number: PCT/JP2010/061394
Authority: WO
Inventors: 蔭山　哲也
Original assignee: 株式会社島津製作所
Priority date: 2010-07-05
Filing date: 2010-07-05
Publication date: 2012-01-12

Abstract

Disclosed is chromatogram display suitable for an analyst to compare chromatograms derived from a plurality of samples with one another to accurately determine/evaluate the similarity or difference of the plurality of samples. When data files in which chromatogram data for each of the samples is stored are given, a display processing unit extracts chromatograms obtained under the same analysis condition/environment (the type of detector is the same, in the case of a UV detector, the wavelength is the same, in the case of a mass spectrometer (MS), m/z is the same, or the like), and overlaps a plurality of the chromatograms derived from the plurality of samples under the same analysis condition/environment in the same graph display frame. The display processing unit overlaps chromatograms under different analysis conditions/environments in different graph display frames, and vertically aligns and displays a plurality of the graph display frames with a time axis as the same. As a result, only meaningful chromatograms are overlapped in one graph display frame to compare the plurality of samples with one another, thus enabling the analyst to easily grasp the difference or similarity of the wavelengths of the chromatograms.

Description

Chromatogram display processor

The present invention is based on data collected by chromatographs such as a gas chromatograph (GC), a liquid chromatograph (LC), a liquid chromatograph mass spectrometer (LC-MS), and a gas chromatograph mass spectrometer (GC-MS). The present invention relates to a chromatogram display processing device for displaying a chromatogram created on a display screen.

For example, in a liquid chromatograph using a photodiode array (PDA) detector, chromatogram data at each wavelength within a predetermined wavelength range can be acquired over time. By specifying a specific wavelength, A chromatogram for the wavelength can be depicted on the display screen. In addition, a liquid chromatograph mass spectrometer can acquire chromatogram data at each mass-to-charge ratio within a predetermined mass-to-charge ratio (m / z) range as time passes. By specifying, a chromatogram (extracted ion chromatogram) for the mass-to-charge ratio can be drawn on the display screen. In addition, in a liquid chromatograph that uses both a mass spectrometer and an ultraviolet-visible spectrophotometer as a detector, both the chromatogram data from the mass spectrometer and the chromatogram data from the ultraviolet-visible spectrophotometer are acquired simultaneously in parallel. One or both chromatograms can be rendered on the display screen.

In the case where a plurality of chromatograms are obtained by one measurement as described above or for one sample, in order to perform waveform processing such as chromatogram cutout processing and comparison processing, the same graph frame is used. Conveniently, multiple chromatograms are rendered. A common way to draw multiple chromatograms in the same graph frame is to share the time axis (horizontal axis) and intensity axis (vertical axis) and change the display color of the chromatogram curve. This is a display method (overlap display) in which a plurality of chromatograms are overlaid. However, the display color becomes unclear in a portion where a large number of chromatogram curves overlap, and there is a problem that it is difficult to distinguish visually. Therefore, in order to improve the recognizability of each chromatogram curve in the overlap display, there is a base shift method in which the time axis is the same and the height of the reference point (baseline) of each chromatogram is gradually changed in the intensity axis direction. It may be adopted (see Patent Documents 1 and 2).

By the way, in general, in a chromatographic apparatus, measurement data collected for one sample is stored in one data file for ease of data management and the like. Therefore, in LC-MS and GC-MS, a single data file stores a plurality of chromatogram data having different mass-to-charge ratios to be observed for a certain sample. In addition, the chromatogram data for a plurality of samples are stored in separate data files.

In chromatographic analysis, it is often the case that different samples containing many of the same or similar components are compared. In such a case, the comparison of the shape of the chromatogram obtained for these multiple samples is analyzed. It is common for a person to visually check. In such a case, if a plurality of chromatograms are displayed in the same graph frame using the conventional overlap display or base shift display, a large number of chromatograms stored in a plurality of data files corresponding to the samples are displayed. It will be displayed overlaid.

However, it is meaningful to judge the similarity or difference of components contained in a plurality of samples, for example, LC-MS and GC-MS are chromatograms for the same mass-to-charge ratio, Finding and comparing chromatograms for the same mass-to-charge ratio of different samples from a large number of chromatograms is a very complicated task. In addition, for example, it is possible to set so that chromatograms for the same mass-to-charge ratio are displayed in the same display color, but even in this case, it is visually identified which chromatogram shape is different for other samples. The analyst can only figure out that there are samples with different chromatogram shapes.

JP 2006-47280 A JP 2007-147464 A

In other words, the conventional chromatogram display method described above is not suitable for the purpose of comparing chromatograms for different samples stored in different data files, which not only imposes a heavy burden on the operator but also makes it more accurate. It was also a factor that hindered evaluation and judgment.

The present invention has been made in view of these problems. In a chromatogram display processing apparatus that creates a chromatogram created based on data collected by chromatographic analysis and displays the chromatogram on a display screen, an analyst can Suitable for visual comparison of chromatograms obtained for multiple samples to evaluate and judge similarity and dissimilarity. In other words, the burden on the analyst is light and does not cause misjudgment. Its purpose is to provide such a display.

The present invention made to solve the above problems is a chromatogram display processing device that creates a chromatogram based on data collected by a chromatograph and displays it on a display screen. In a chromatogram display processing device that processes data stored in a format that stores various chromatogram data collected in a single data file,
a) data selection means for extracting chromatogram data under the same conditions and the same environment for each data file for a plurality of data files corresponding to a plurality of samples;
b) A plurality of chromatograms created from chromatogram data under the same conditions and the same environment extracted by the data selection means are overlaid on the same time axis and intensity axis graphs in a mutually distinguishable manner. A drawing means for drawing and displaying;
It is characterized by having.

The “chromatograph device” in the present invention is a liquid chromatograph or a gas chromatograph, and its detector is a mass spectrometer, an ultraviolet-visible spectroscopic detector, a photodiode array (PDA) spectroscopic detector, a spectrofluorescence detector, etc. Any detection method may be used. Moreover, the structure which used several detector together may be sufficient.

The above “same conditions / same environment” means that if the detector is a mass spectrometer, the same mass-to-charge ratio or mass-to-charge ratio range (including the entire mass-to-charge ratio range), and the detector is an ultraviolet-visible spectroscopic detector If the detector is a PDA spectroscopic detector, the same wavelength (center wavelength) and wavelength bandwidth, if the detector is a spectroscopic fluorescence detector, the same excitation light wavelength and fluorescence wavelength, etc. is there. Further, in the case of a configuration in which a plurality of detectors are used in combination, the “same conditions / same environment” naturally includes that the types of detectors are the same.

A “chromatogram” is not only a temporal change in the detection signal (signal intensity) obtained by the detector, but also the time of the signal obtained by performing appropriate waveform processing and data processing on such a signal. It may be a sign of change. Therefore, for example, when the detector is a mass spectrometer, the chromatogram is obtained by adding or subtracting the extracted ion chromatograms for a plurality of mass-to-charge ratios in addition to the total ion current chromatogram and the extracted ion chromatogram. Also included are base peak chromatograms, mass-defect chromatograms, isotopic filtered chromatograms, neutral loss chromatograms, etc. that collect the peaks with the highest ionic strength. When the chromatogram is obtained through waveform processing or data processing, the above “same conditions / same environment” means that the conditions of waveform processing and data processing are also the same.

Further, the chromatogram display processing apparatus according to the present invention provides a dedicated computer program for realizing functions corresponding to the data selection means and the drawing means on a general-purpose computer including a display section, an operation section (keyboard, pointing device, etc.), etc. It can be realized by executing.

Taking a case where the chromatogram display processing apparatus according to the present invention is applied to a liquid chromatograph mass spectrometer as an example, the data selection means, for a plurality of data files corresponding to a given plurality of samples, for each data file. Chromatogram (extracted ion chromatogram) data having the same mass-to-charge ratio is extracted. Therefore, the same number of chromatogram original data as the number of samples and the same number of data files are extracted. Then, the drawing means changes a plurality of chromatograms respectively created from the chromatogram data extracted by the data selection means into a mutually distinguishable manner, typically by changing the display color of each chromatogram curve, And overlaid on the graph of intensity axis.

When the same chromatogram is extracted with different mass-to-charge ratios for multiple data files, the chromatograms may be overlaid and displayed in different graph display frames for each mass-to-charge ratio. However, because the number of graph display frames that can be displayed simultaneously is limited due to the size of the display screen, if there are many mass-to-charge ratios, for example, a chromatogram for the mass-to-charge ratio specified by the analyst. Only need to be displayed.

Also, when providing a plurality of graph display frames as described above, it is preferable to employ a stack (shelf) display in which a plurality of graph display frames are arranged in the vertical direction with the time axis as a horizontal axis in common.

In addition, when any one of a plurality of chromatograms displayed in one graph display frame is expanded or reduced in the common time axis direction or intensity axis direction, other chromatograms in the same graph display frame are displayed. The gram may be enlarged or reduced in conjunction with it. In the case of the stack display as described above, when any one of a plurality of chromatograms displayed in a certain graph display frame is enlarged or reduced in the common time axis direction, the other is displayed. All the chromatograms displayed in the graph display frame may be enlarged or reduced in conjunction with each other.

In addition, although only a chromatogram under the same conditions and the same environment is displayed in one graph display frame, if the number of samples is large, the chromatogram curves may overlap and become difficult to see. Therefore, it is preferable that a plurality of chromatograms in an arbitrary graph display frame can be displayed in base shift. Thereby, even when the number of chromatograms is large, the distinguishability of each chromatogram can be improved.

In addition, the chromatogram display by the chromatogram display processing apparatus according to the present invention is very useful for comparing a plurality of samples, but it is possible to compare the entire extracted ion chromatogram or to determine the shape of a specific chromatogram. It is not always suitable when you want to observe in detail. Therefore, “comparison display” as in the present invention and other, for example, all chromatograms of all data files are overlaid and displayed in one graph display frame, “all overlap display”, and one chromatogram is displayed. Multiple different display modes can be switched between menu and tab formats, such as “parallel display”, which draws images in one graph display frame, and “single display”, which draws only one selected chromatogram. Good.

According to the chromatogram display processing apparatus according to the present invention, for example, a plurality of chromatograms for different samples having the same mass-to-charge ratio and wavelength are automatically extracted and superimposed on a graph that is a common axis. Is displayed. Therefore, the comparison of chromatogram shapes for a plurality of samples can be performed accurately and easily, work efficiency is improved, and work errors are reduced, so that the reliability of the results is increased.

The schematic block diagram of one Example of LC analysis system containing the chromatogram display processing apparatus which concerns on this invention. The flowchart which shows an example of the characteristic display processing operation in the LC analysis system of a present Example. The schematic diagram which shows an example of the display screen in the LC analysis system of a present Example. The schematic diagram which shows an example of the display screen in the LC analysis system of a present Example. The schematic diagram which shows an example of the display screen in the LC analysis system of a present Example.

Hereinafter, an LC analysis system including a chromatogram display processing apparatus according to the present invention will be described with reference to the accompanying drawings. FIG. 1 is a schematic configuration diagram of an LC analysis system according to the present embodiment.

This system includes a liquid chromatograph (LC unit) 1 that temporally separates components contained in a sample, and an ultraviolet-visible spectroscopic detector (UV detector) that is a first detector that detects each separated component. 2, a mass spectrometer (MS unit) 3 that separates and detects each component in the sample that has passed through the UV detector 2 according to the mass-to-charge ratio (m / z), and the UV detector 2 and the MS unit 3. The data processing unit 4 that processes the data acquired in step S4, the data storage unit 6 for storing measurement data, the operation unit 7 that is a pointing device such as a keyboard and a mouse, and the display unit 8 are included. The data processing unit 4 and the data storage unit 6 can be configured around a general-purpose personal computer. By executing dedicated data processing software preinstalled in the personal computer on the computer, the display processing unit 5, functions such as the data processing unit 4 and the data storage unit 6 are realized.

In the LC analysis system of this embodiment, chromatogram data is acquired as follows and stored in the data storage unit 6. That is, when a sample is introduced into the LC unit 1, the components contained in the sample are separated and eluted in time while passing through a column (not shown). The UV detector 2 repeatedly measures the absorbance at one or more preset wavelengths at predetermined time intervals. On the other hand, the MS unit 3 repeatedly measures the signal intensity corresponding to the ion amount at one or more preset mass to charge ratios at predetermined time intervals. The MS unit 3 may repeat scan measurement in a predetermined mass-to-charge ratio range.

By the above measurement, the UV detector 2 obtains chromatogram data from the sample injection point to the sample elution end point for every one or a plurality of wavelengths, and the MS unit 3 starts from the sample injection point for every one to a plurality of mass-to-charge ratios. Chromatogram data up to the end of sample elution is obtained. All the data collected in one measurement performed on one sample is collected into one data file and stored in the data storage unit 6. When another sample is introduced into the LC unit 1 and similarly the chromatogram data is collected by the UV detector 2 and the MS unit 3, it is aggregated into another data file and stored in the data storage unit 6. The Therefore, as many data files as the number of samples are created and stored in the data storage unit 6. As shown in FIG. 1, in one data file corresponding to one sample, an area for storing chromatogram data obtained by the UV detector 2 and chromatogram data obtained by the MS unit 3 are stored. In addition, the former stores the chromatogram data separately for each wavelength λ and the latter for each mass to charge ratio m / z. Note that the measurement wavelength in the UV detector 2 and the observed mass-to-charge ratio in the MS unit 3 when measuring a plurality of samples do not need to be completely the same, and different values are set for each sample in part. It is possible.

When the analyst designates the type of sample to be compared (for example, a serial number attached to the sample, an appropriate sample name, etc.) from the operation unit 7 and instructs execution of “comparison display” of the chromatogram, this instruction The display processing unit 5 that has received the data appropriately reads out the data stored in the data storage unit 6 and executes a characteristic display process, and displays the resulting graph on the screen of the display unit 8. This chromatogram display process will be described with reference to the flowchart of FIG.

First, the display processing unit 5 reads data files for a plurality of designated samples from the data storage unit 6 (step S1). In this example, it is assumed that two types of samples A and B are designated as samples to be compared and displayed. In this case, two data files, a data file for the sample A and a data file for the sample B, are read into the display processing unit 5. An outline of the read data file is shown in FIG.

Next, the display processing unit 5 extracts chromatogram data under the same conditions and the same environment for the two data files (step S2). Here, “same conditions / same environment” means that the type of the detector (the UV detector 2 or the MS unit 3) is the same, that the data by the UV detector 2 has the same wavelength, the MS unit 3 In the data, the mass-to-charge ratio is the same. Therefore, the display processing unit 5 recognizes from the two data files that there is chromatogram data with the detector type UV detector 2 and the measurement wavelength both λ2, and the detector type is the MS unit. After recognizing that there is chromatogram data in which the mass-to-charge ratio observed in 3 is both m / z1, these data are extracted. Then, a chromatogram is created from each of these data (step S3).

Subsequently, the display processing unit 5 corrects the time axis of the created chromatogram and performs waveform processing such as normalizing the intensity as necessary (step S4). In the LC analysis system of this embodiment, since the sample liquid after passing through the UV detector 2 reaches the MS section 3 and is detected, the chromatogram data in the UV detector 2 and the chromatogram data in the MS section 3 In the meantime, there is a time lag for the time required for the sample liquid to flow from the UV detector 2 to the MS unit 3. When there is such a time lag, it is necessary to correct the time axis of the chromatogram. Since the amount of time shift depends on the moving speed of the mobile phase (eluent) in the LC unit 1 and the mechanical conditions such as the channel length from the UV detector 2 to the MS unit 3, It can be calculated with high accuracy. Therefore, the display processing unit 5 corrects the time axis of the chromatogram based on the calculated time shift amount. Thereby, comparison between chromatograms by different detectors is also possible. Further, when it is desired to display the intensity axis of the chromatogram as a relative value based on the maximum intensity, for example, intensity normalization is also executed.

For the chromatograms derived from the sample A and the sample B that have been corrected for time axis as described above, the display processing unit 5 converts the two chromatograms obtained by the UV detector 2 and having both wavelengths λ2 into a time axis and an intensity axis. Is superimposed on one graph display frame, while two chromatograms obtained by the MS unit 3 and having a mass-to-charge ratio of m / z1 are combined with another one having a common time axis and intensity axis. Overlay in the graph display frame. When overlaying, the display colors of the two chromatogram curves in the same graph display frame are changed so that the chromatogram curves for the same sample have the same color. Further, the time axes of the two graph display frames are set in common, and the two graph display frames are arranged side by side vertically and then displayed on the screen of the display unit 8 (step S5). In FIG. 4B, the chromatogram by the UV detector 2 is displayed on the top, and the chromatogram by the MS unit 3 is displayed on the bottom. In this figure, since the color cannot be expressed, the chromatogram curve derived from the sample B is indicated by a solid line, and the chromatogram curve derived from the sample A is indicated by a one-dot chain line.

The chromatograms derived from Sample A and Sample B displayed in the same graph display frame are chromatograms at the same wavelength and mass-to-charge ratio, and the absorption wavelength and mass-to-charge ratio are specific to the substance. By comparing the peak positions, heights, shapes, etc. of these chromatograms, a person can easily evaluate the similarity or difference between the two samples. In addition, since the time axes of the two graph display frames are common, as shown in FIG. 4A, the analyst can enlarge or reduce the time axis of the chromatogram in one of the graph display frames. When an operation is performed with a mouse or the like, as shown in FIG. 4B, the time of the chromatogram in the other graph display frame is interlocked with the expansion or contraction of the time axis of the chromatogram in the graph display frame. The axis is also enlarged or reduced. Therefore, the shapes of all chromatograms can always be compared under the same time axis.

In addition, in the example of FIG. 3, only the chromatograms of two samples are overlaid, so there is no problem in the distinguishability of the overlapping part, but when the chromatograms of many samples are overlaid. In some cases, the discriminability at the part where the lines overlap is deteriorated. Therefore, as shown in FIG. 5, when the analyst performs a predetermined operation from the operation unit 7, a plurality of chromatograms derived from different samples displayed in the same graph display frame are shifted in the time axis direction. The shift display is configured. Thereby, the distinguishability of a large number of chromatograms is improved, and peak waveforms can be easily compared.

FIG. 3B shows a particularly convenient display when comparing a plurality of samples. In some cases, for example, it is desirable to compare chromatograms at all mass-to-charge ratios or to compare specific mass-to-charge ratios. There are various requests such as wanting to confirm only the chromatogram in detail. Therefore, in addition to the above-mentioned “comparison display”, all chromatograms in all specified data files are overlaid and displayed in one graph display frame, “all overlap display”, one chromatogram is 1 It is possible to switch between multiple different display modes in the menu format or tab format, such as “Parallel display” that draws them in one graph display frame, and “Single display” that draws only one selected chromatogram. Good.

The analysis system of the above embodiment is a combination of a UV detector and an MS unit as a detector. However, an LC device equipped with only a UV detector or an LC device equipped with only an MS unit (ie, LC-MS). When the chromatogram display processing apparatus according to the present invention is applied, chromatograms derived from a plurality of samples are overlaid and displayed in the same graph display frame at the same wavelength or the same mass-to-charge ratio. The chromatogram display processing apparatus according to the present invention is an apparatus that performs not only data collected by LC analysis but also chromatographic analysis that detects a plurality of substances contained in a sample by separating them in time. In addition, data collected by an apparatus capable of acquiring a plurality of types of chromatogram data under different conditions / environments for one sample can be processed.

Furthermore, in addition to the above description, it is obvious that modifications, corrections, and additions may be made as appropriate within the scope of the present invention and included in the scope of claims of the present application.

DESCRIPTION OF SYMBOLS 1 ... LC part 2 ... UV detector 3 ... MS part 4 ... Data processing part 5 ... Display processing part 6 ... Data storage part 7 ... Operation part 8 ... Display part

Claims

A chromatogram display processing device that creates a chromatogram based on data collected by a chromatograph device and displays the chromatogram on a display screen. Various chromatogram data collected for one sample is stored as one data. In a chromatogram display processing device that processes data saved in a format that is stored together in a file,
a) data selection means for extracting chromatogram data under the same conditions and environment for each data file for a plurality of data files corresponding to a plurality of samples;
b) A plurality of chromatograms created from chromatogram data under the same conditions and the same environment extracted by the data selection means are overlaid on the same time axis and intensity axis graphs in a mutually distinguishable manner. A drawing means for drawing and displaying;
A chromatogram display processing device comprising:
The chromatogram display processing device according to claim 1,
The drawing means draws a plurality of chromatograms derived from a plurality of samples in different graph display frames every time conditions and environments differ, and the plurality of graph display frames are vertically aligned with a horizontal axis as a time axis. A chromatogram display processing device, characterized by being arranged and displayed in a direction.
The chromatogram display processing device according to claim 2,
When any one of a plurality of chromatograms displayed in one graph display frame among the plurality of graph display frames is expanded or reduced in the common time axis direction, A chromatogram display processing device, wherein all chromatograms displayed on the screen are also enlarged or reduced in conjunction with each other.