Data processing device and data processing method

Abstract

A chromatogram (G10) and a chromatogram (G20) are chromatograms acquired in measurements according to different conditions. This data processing device separates the chromatogram (G10) into peaks (peaks (P11 to P17)). The data processing device further separates the chromatogram (G20) into peaks (peaks (P21 to P27)). The data processing device then associates the peaks (P11 to P17) with the peaks (P21 to P27) and displays the result of the association.

Description

Data processing device, data processing method, program, and chromatography system

[0001] The present invention relates to data processing, and in particular to processing data relating to the analysis of samples.

[0002] In sample analysis, there is a technique called comprehensive two-dimensional chromatography. Comprehensive two-dimensional chromatography, as described in Japanese Patent No. 5347932 (Patent Document 1) or Japanese Patent No. 6828833 (Patent Document 2), utilizes a primary column and a secondary column having separation characteristics different from those of the primary column. More specifically, in comprehensive two-dimensional chromatography, components eluted from the primary column are collected at regular time intervals and sent to the secondary column in a time-compressed manner.

[0003] Comprehensive two-dimensional chromatography separates a sample according to the different separation characteristics of the first and second columns. This allows for the separation of two or more components in a sample that could not be separated using only the first or second column. Therefore, comprehensive two-dimensional chromatography can provide users with information that allows for detailed analysis of the sample.

[0004] Patent No. 5347932 Patent No. 6828833

[0005] However, comprehensive two-dimensional chromatography has many problems as described below, and the above-mentioned analyses require a great deal of effort on the part of the user.

[0006] That is, an expensive dedicated system is required to deliver the components eluting from the primary column to the secondary column as described above.

[0007] Furthermore, comprehensive two-dimensional chromatography is prone to a phenomenon known as peak splitting, and it is necessary to consider the conditions to avoid this phenomenon. In this regard, comprehensive two-dimensional chromatography uses different separation systems for the primary and secondary columns, which means that there are many analytical condition parameters, making it difficult to predict which parameters should be changed and how to achieve the desired results, and therefore making the consideration of conditions very difficult.

[0008] Furthermore, comprehensive two-dimensional chromatography requires a very long time for a single analysis, from 30 minutes to several hours, making the above-mentioned condition studies highly difficult and requiring a long time to obtain the necessary materials.

[0009] Furthermore, since the system configuration for achieving comprehensive two-dimensional chromatography is complex, it is difficult to determine the cause when an error in analytical conditions or a malfunction in the device occurs.

[0010] In the first place, in comprehensive two-dimensional chromatography, due to the system configuration, analysis using the secondary column must be performed at an ultra-high speed of about one minute, which often results in insufficient separation ability being achieved in analysis using the secondary column.

[0011] The present invention has been devised in view of the above circumstances, and its purpose is to provide a technology that can provide a user with information that enables detailed examination of a sample and reduces the burden on the user.

[0012] According to one aspect of the present disclosure, there is provided a data processing device for processing data, the data processing device including an interface and a calculation device that acquires, via the interface, a first chromatogram of a sample obtained under first conditions and a second chromatogram of the sample obtained under second conditions, the calculation device separates the first chromatogram into a first group of peaks, separates the second chromatogram into a second group of peaks, associates each of the peaks included in the first group of peaks with each of the peaks included in the second group of peaks, and displays the results of the association.

[0013] According to another aspect of the present disclosure, there is provided a chromatography system including a data processing device and a chromatograph, wherein the data processing device includes a computing device that acquires from the chromatograph a first chromatogram obtained under first conditions for a sample and a second chromatogram obtained under second conditions for the sample, separates the first chromatogram into a first group of peaks, separates the second chromatogram into a second group of peaks, associates each of the peaks included in the first group of peaks with each of the peaks included in the second group of peaks, and displays the results of the association.

[0014] According to one aspect of the present disclosure, there is provided a technology that can provide a user with information that enables detailed examination of a sample and reduces the burden on the user.

[0015] FIG. 1 is a diagram illustrating a configuration of a chromatography system 1 according to an embodiment. FIG. 2 is a diagram illustrating a specific example of generation of a virtual multidimensional chromatogram. FIG. 3 is a diagram illustrating another example of the processing results of two chromatograms G10 and G20. FIG. 4 is a diagram illustrating an example of the results of mass analysis of a certain sample. FIG. 5 is a diagram illustrating three-dimensional data composed of a spectrum vector and a chromatogram. FIG. 6 is a diagram illustrating an example of the relationship between a spectrum, a chromatogram vector, and each matrix expression of the spectrum vector. FIG. 7 is a diagram illustrating another example of the relationship between a spectrum, a chromatogram vector, and each matrix expression of the spectrum vector. FIG. 8 is a diagram illustrating peak correspondence. FIG. 9 is a flowchart of processing performed by the data processing device 100 for matching peaks in multiple chromatograms. FIG. 10 is a diagram illustrating a first specific example of displaying the results of the correspondence. FIG. 11 is a diagram illustrating a second specific example of displaying the results of the correspondence. FIG. 12 is a diagram illustrating the correspondence between a peak in a chromatogram 620 and a peak in a chromatogram 640.

[0016] Hereinafter, embodiments of the present disclosure will be described in detail with reference to the drawings. In the drawings, the same or corresponding parts are designated by the same reference numerals, and description thereof will not be repeated.

[0017] [Chromatography System] The configuration of a chromatography system 1 according to an embodiment will be described with reference to Fig. 1. Fig. 1 is a diagram showing the configuration of the chromatography system 1 according to an embodiment. As shown in Fig. 1, the chromatography system 1 includes a chromatograph 10, an analyzer 20, and a data processing device 100.

[0018] (Chromatograph 10) In this specification, a liquid chromatograph (LC) using a liquid as a mobile phase is described as a specific example of the chromatograph 10. However, the chromatograph 10 may be another type of chromatograph, such as a gas chromatograph using a gas as a mobile phase.

[0019] The chromatograph 10 includes a container 11 , a liquid pump 12 , an injector 13 , a column 14 , and a UV measuring instrument 15 .

[0020] The container 11 contains a mobile phase. The liquid delivery pump 12 draws the mobile phase from the container 11 and delivers it at a constant flow rate. The injector 13 injects a sample to be analyzed into the mobile phase delivered by the liquid delivery pump 12. The column 14 contains a stationary phase and separates various components contained in the sample injected by the injector 13. The UV measuring instrument 15 measures the absorbance of light of a given wavelength for the eluate from the column 14.

[0021] A sample to be analyzed is injected into the mobile phase by the injector 13. The injected sample is carried along with the flow of the mobile phase delivered by the liquid delivery pump 12 to reach the column 14 and pass through the column 14.

[0022] The various components contained in the sample take different amounts of time to pass through the column 14 depending on their affinity with the stationary phase or the mobile phase. For example, among the components contained in the sample, components that are easily adsorbed to the stationary phase take longer to pass through the column 14 (also referred to as "retention time") than components that are less easily adsorbed to the stationary phase. In this way, the various components contained in the sample are separated in the time direction by the column 14. The eluate containing the components separated in the column 14 is introduced from the column 14 into the UV measuring instrument 15.

[0023] The UV measuring instrument 15 includes a flow cell into which the eluate from the column 14 is introduced, a UV lamp that irradiates the eluate flowing through the flow cell with ultraviolet light of a given wavelength, and a UV detecting element that measures the intensity of the ultraviolet light that has passed through the flow cell. The UV measuring instrument 15 transmits the measurement results obtained for the eluate to the data processing device 100. The eluate from the UV measuring instrument 15 is introduced into the analyzer 20.

[0024] (Analyzer 20) The analyzer 20 acquires the sample as an eluate from the UV measuring instrument 15, analyzes the sample, and transmits the analysis results to the data processing device 100. The analyzer 20 is, for example, an absorbance measuring instrument (a PDA (Photo Diode Array) measuring instrument), a fluorescence measuring instrument, a differential refractive index measuring instrument, a conductivity measuring instrument, or a mass spectrometer.

[0025] (Data Processing Device 100) The data processing device 100 is, for example, a general-purpose computer. The data processing device 100 may be a computer dedicated to the chromatography system 1 for processing detection data from the chromatograph 10. The data processing device 100 includes an arithmetic unit 101, a memory 102, a storage device 103, and an interface 104.

[0026] The arithmetic device 101 is a computing entity (computer) that executes various processes by executing various programs. The arithmetic device 101 is configured with a processor such as a central processing unit (CPU) or a microprocessing unit (MPU). The processor, which is an example of the arithmetic device 101, has the function of executing various processes by executing programs. The data processing device 100 may implement some or all of these functions using dedicated hardware circuits such as an application-specific integrated circuit (ASIC) or a field-programmable gate array (FPGA) in addition to or instead of the arithmetic device 101. The term "processor" is not limited to a processor in the narrow sense that executes processes using a stored program, such as a CPU or MPU, but may also include hardwired circuits such as an ASIC or FPGA. Therefore, the "processor" as an example of the arithmetic device 101 may also be interpreted as a processing circuit whose processes are predefined by computer-readable code and / or hardwired circuits. The computing device 101 may be configured as a single chip or multiple chips. Furthermore, the processor and related processing circuits may be configured as multiple computers interconnected by wire or wirelessly via a local area network or a wireless network. The processor and related processing circuits may be configured as a cloud computer that performs remote calculations based on input data and outputs the calculation results to another device in a remote location.

[0027] The memory 102 includes a volatile storage area (for example, a working area) that temporarily stores program code, work memory, etc. when the arithmetic device 101 executes various programs. Examples of the storage unit include volatile memories such as DRAM (dynamic random access memory) and SRAM (static random access memory), and non-volatile memories such as ROM (read only memory) and flash memory.

[0028] The storage device 103 stores various programs and various data executed by the arithmetic device 101. The storage device 103 may be one or more non-transitory computer-readable media or one or more computer-readable storage media. Examples of the storage device 103 include a hard disk drive (HDD) and a solid state drive (SSD). The storage device 103 according to the embodiment stores a data processing program 130 for executing data processing in which the arithmetic device 101 processes detection data acquired from the chromatograph 10.

[0029] The interface 104 transmits and receives data to and from an external device or equipment via wired or wireless communication. For example, the interface 104 communicates with the chromatograph 10 to acquire detection data output from the chromatograph 10. The interface 104 may also be a communication device that communicates with a cloud server (not shown) to transmit detection data acquired from the chromatograph 10 to the cloud server or transmits execution results of data processing from the arithmetic device 101 to the cloud server. Furthermore, the interface 104 may transmit and receive data to and from the display unit 110 or input unit 120, which are user interfaces, via wired or wireless communication. The data processing device 100 is not limited to having one interface 104, but may have multiple interfaces 104 depending on the number of communication targets.

[0030] The display unit 110 is, for example, a display configured with a liquid crystal panel or the like, and displays the results of data processing performed by the data processing device 100 (for example, the calculated Levenshtein distance). The input unit 120 is, for example, a pointing device such as a keyboard or a mouse, and receives commands from a user. When a touch panel is used as the user interface, the display unit 110 and the input unit 120 may be integrally formed. Note that the display unit 110 and the input unit 120 may be configured to be included in the data processing device 100.

[0031] In the chromatography system 1 configured as described above, the data processing device 100 acquires detection data from the chromatograph 10 via the interface 104. The detection data includes signal intensities measured by the UV measuring instrument 15. The data processing device 100 generates a chromatogram showing the time change of the signal intensities included in the detection data.

[0032] The data processing device 100 also obtains from the analyzer 20 the analysis results of the sample for which the chromatogram was generated.

[0033] [Data Processing (1)] In the chromatography system 1, a user performs measurements on a certain sample using the chromatograph 10 multiple times under different conditions. One example of a condition is the type of mobile phase used. For example, a first analysis of a certain sample is performed under the condition that water is used as the mobile phase, and then a second analysis is performed under the condition that methanol is used as the mobile phase. Another example of a condition is the type of stationary phase used. Yet another example of a condition is the type of combination of mobile phase and stationary phase used.

[0034] By performing measurements multiple times under different conditions as described above, the data processing device 100 generates multiple chromatograms for a certain sample acquired under different conditions, and then integrates the multiple chromatograms to generate a virtual multidimensional chromatogram.

[0035] 2 is a diagram illustrating a specific example of generating a virtual multidimensional chromatogram. Four stages ST1, ST2, ST3, and ST4 are shown in FIG. 2. In stage ST1, the data processing device 100 acquires (generates) two chromatograms G10 and G20. In each of the chromatograms G10 and G20, the horizontal axis represents retention time, and the vertical axis represents signal intensity.

[0036] Chromatogram G10 appears to include four peaks P0, P1, P2, and P3. Peaks P0 and P3 each have an outline that appears to include multiple peaks.

[0037] Chromatogram G20 appears to include six peaks P4, P5, P6, P7, P8, and P9. Peak P9 has an outline that appears to include multiple peaks.

[0038] In step ST2, the data processing device 100 performs processing for peak separation on each of the chromatograms G10 and G20.

[0039] A group of peaks is identified from chromatogram G10 through processing for peak separation. The group of peaks identified from chromatogram G10 is shown as seven peaks P11 to P17 in chromatogram G11. A group of peaks is also identified from chromatogram G20. The group of peaks identified from chromatogram G20 is shown as seven peaks P21 to P27 in chromatogram G21. Note that in each of chromatograms G11 and G21, the horizontal axis represents retention time and the vertical axis represents signal intensity, similar to chromatograms G10 and G20.

[0040] In stage ST3, the data processing device 100 performs peak correspondence between the chromatogram G11 and the chromatogram G21, thereby corresponding each of the seven peaks included in the chromatogram G11 to each of the seven peaks included in the chromatogram G21.

[0041] In peak matching, a peak in chromatogram G11 is selected, and a peak in chromatogram G21 that is thought to represent the same component as the component represented by the selected peak is identified as the peak corresponding to the selected peak. Then, for all peaks in chromatogram G11, corresponding peaks in chromatogram G21 are identified.

[0042] 2, in stage ST3, the peaks included in chromatogram G11 and the peaks included in chromatogram G21 are connected by dashed lines. More specifically, peaks P11, P12, P13, P14, P15, P16, and P17 in chromatogram G11 correspond to peaks P22, P23, P21, P25, P26, P24, and P27 in chromatogram G21, respectively.

[0043] In step ST4, the data processing device 100 combines the chromatogram G11 and the chromatogram GG21 to generate a chromatogram G30. In the chromatogram G30, the vertical axis represents the retention time in the chromatogram G11, and the horizontal axis represents the retention time in the chromatogram G21. The chromatogram G30 is a virtual two-dimensional chromatogram generated based on the chromatogram G11 and the chromatogram G21.

[0044] Chromatogram G30 is an example of a display of the results of peak matching in stage ST3. More specifically, chromatogram G30 includes seven peaks P31, P32, P33, P34, P35, P36, and P37.

[0045] Peaks P31, P32, P33, P34, P35, P36, and P37 are located at the intersections of the retention times of peaks P11, P12, P13, P14, P15, P16, and P17, respectively, and the retention times of peaks P22, P23, P21, P25, P26, P24, and P27, respectively, of chromatogram G21. For example, peak P31 is located at the intersection of peaks P11 and P22. Peak P32 is located at the intersection of peaks P12 and P23.

[0046] The shading of peaks P31, P32, P33, P34, P35, P36, and P37 is determined by the product of the signal intensities of peaks P11, P12, P13, P14, P15, P16, and P17 and the signal intensities of peaks P22, P23, P21, P25, P26, P24, and P27 in chromatogram G21. For example, the shading of peak P31 is determined by the product of the signal intensities of peak P11 and peak P22. Similarly, the shading of peak P32 is determined by the product of the signal intensities of peaks P12 and P23.

[0047] In chromatogram G30, the shade of the peak displayed at the intersection of the peak of chromatogram G10 and the peak of chromatogram G20 is determined by the product of the signal intensity of the peak of chromatogram G10 and the signal intensity of the peak of chromatogram G20, so that in chromatogram G30, the signal intensity of the peak of chromatogram G10 and the signal intensity of the peak of chromatogram G20 are more emphasized.

[0048] Chromatogram G30 is an example of a "three-dimensional representation" of the sample analyzed by chromatogram G11 and chromatogram G21, with respect to three dimensions: (1) retention time in chromatogram G11, (2) retention time in chromatogram G21, and (3) the product of the signal intensity in chromatogram G11 and the signal intensity in chromatogram G21. The product of the signal intensity in chromatogram G11 and the signal intensity in chromatogram G21 is an example of a value based on the signal intensity in chromatogram G11 and the signal intensity in chromatogram G21. Another example is the sum of these signal intensities. Yet another example is a calculated value according to a function of these signal intensities.

[0049] The data processing device 100 may display the chromatogram G30 as an example of the processing result of the two chromatograms G10 and G20. The data processing device 100 may also display the chromatograms G10 and G20 simultaneously with the chromatogram G30 as an example of the processing result.

[0050] The chromatogram G30 is a virtual two-dimensional chromatogram, and a three-dimensional representation is realized by a two-dimensional graph and the concentrations of regions in the graph. Note that the chromatogram G30 may be represented by a three-dimensional graph with the above three dimensions as three axes.

[0051] The data processing device 100 can also generate virtual multidimensional chromatograms for three or more chromatograms obtained by experiments under mutually different conditions.

[0052] For example, the data processing device 100 may perform deconvolution to separate peaks in each of three chromatograms (first chromatogram, second chromatogram, and third chromatogram), perform peak tracking to match the peaks in the three chromatograms with the peaks in each of the remaining two chromatograms, and then combine the three chromatograms to generate a virtual three-dimensional chromatogram.

[0053] The virtual three-dimensional chromatogram is, for example, a three-dimensional graph with the retention times of the first to third chromatograms as axes, and the color intensity of each peak displayed in the three-dimensional graph is adjusted according to the product of the signal intensity of the corresponding point in the first chromatogram, the signal intensity of the corresponding point in the second chromatogram, and the signal intensity of the corresponding point in the third chromatogram.

[0054] [Data Processing (2)] Fig. 3 is a diagram for explaining another example of the processing results of two chromatograms G10 and G20. Fig. 3 shows a table. The data processing device 100 may display the table of Fig. 3 as an example of the processing results of the two chromatograms G10 and G20.

[0055] The table includes information on the seven peaks in chromatogram G20 that correspond to the seven peaks separated in chromatogram G10.

[0056] 3, the peaks extracted from each of the chromatograms G10 and G20 are associated with "peak numbers." Peak numbers are assigned in order of the retention times at which peaks appear in each chromatogram, starting with the earliest peak.

[0057] The data processing device 100 generates and displays a table such as that shown in FIG. 3 using the results of the peak correlation (correspondence between peaks) described in step ST3 with reference to FIG.

[0058] 3, the extracted peaks for each of chromatograms G10 and G20 are arranged in order of peak number. Peaks in chromatogram G10 are connected to their corresponding peaks in chromatogram G20 by dashed lines. For example, peak P11 is connected to peak P22 by a dashed line.

[0059] The table in Fig. 3 uses dashed lines to indicate the correspondence between the peak numbers of each peak in chromatogram G10 and each peak in chromatogram G20. The peak numbers are an example of peak information. The peak information may be the retention time itself or the analysis results of the analyzer 20 corresponding to each peak. In other words, the data processing device 100 may display the retention times of corresponding peaks or the analysis results of corresponding peaks instead of or in addition to the table in Fig. 3.

[0060] [Peak Separation] As an example of peak separation in the above-mentioned stage ST2, deconvolution will be described.

[0061] In deconvolution, a "chromatogram vector" is assumed to be generated from a chromatogram for a given sample. A "spectrum" is obtained for the sample using a given analytical method (performed by the analyzer 20), and a "spectrum vector" is generated from the spectrum.

[0062] Note that deconvolution is based on the premise that when the spectrum is expressed as a matrix, the matrix can be expressed as the product of a matrix representing one or more "chromatogram vectors" and a matrix representing the "spectrum vector."

[0063] Based on this premise, in deconvolution, the spectrum matrix is ​​decomposed into two matrices, one of which is considered to be a chromatogram vector matrix and the other is considered to be a spectrum vector matrix. Each column of the chromatogram vector matrix obtained by the decomposition is considered to be a vector representing the peak of each component of the sample. Then, the peak of each component is extracted from the chromatogram (of the entire sample) as a waveform corresponding to the vector representing the peak of each component. Deconvolution will be described in more detail below.

[0064] In the following example, mass spectrometry is used as an example of the "given analysis method." Fig. 4 is a diagram showing an example of the results of mass spectrometry of a certain sample. Calculation of a spectral vector will be described with reference to Fig. 4. Fig. 4 shows the results of mass spectrometry of a certain sample.

[0065] The spectral vector is calculated using signal intensities based on the spectrum shown in Fig. 4. In the example of Fig. 4, the signal intensities include a signal intensity of "30" when the mass-to-charge ratio is "100", a signal intensity of "50" when the mass-to-charge ratio is "200", and a signal intensity of "400" when the mass-to-charge ratio is "300".

[0066] A spectral vector is then generated using the signal intensities at multiple points on the spectrum.

[0067] Similarly to the generation of a spectrum vector from a spectrum, a chromatogram vector is also generated using the signal intensities of multiple points on a chromatogram.

[0068] Fig. 5 is a diagram showing three-dimensional data composed of a spectral vector and a chromatogram, in which the first axis represents the mass-to-charge ratio, the second axis represents the retention time, and the third axis represents the signal intensity.

[0069] The spectrum shown in Fig. 4 was acquired for an eluate introduced from the chromatograph 10 into the analyzer 20 at a certain timing. The data processing device 100 calculates spectral vectors for the spectra acquired at each of the multiple timings and arranges these spectral vectors in chronological order for each retention time, thereby generating three-dimensional vector data such as that shown in Fig. 5.

[0070] The chromatogram can be considered as a projection of the three-dimensional graph of Fig. 5 onto a two-dimensional graph, with the horizontal axis representing the retention time in Fig. 5 and the vertical axis representing the value corresponding to the signal intensity in Fig. 5. Thus, in this embodiment, it is assumed that the chromatogram represents the time change of the spectrum vector.

[0071] Based on the above assumption, in this embodiment, it is assumed that when the spectrum is expressed as a matrix, the matrix is ​​the product of a matrix representing one or more "chromatogram vectors" and a matrix representing the "spectrum vector."

[0072] FIG. 6 is a diagram showing an example of the relationship between the matrix expressions of a spectrum, a chromatogram vector, and a spectrum vector.

[0073] 6, matrix M10 represents a matrix of chromatogram vectors. Line L10 represents an example of a chromatogram corresponding to matrix M10. Matrix M20 represents a matrix of spectrum vectors. Line L20 represents an example of a spectrum corresponding to matrix M20. Matrix M30 represents a matrix of spectra. In matrix M30, the row direction corresponds to changes in time (retention time in the chromatogram), and the column direction corresponds to changes in mass-to-charge ratio in the spectrum.

[0074] The spectrum matrix M30 corresponds to the three-dimensional data shown in Fig. 5. More specifically, in the matrix M30, each row represents a spectrum at a certain timing, i.e., the signal intensity for each mass-to-electric field ratio detected at a certain timing. For example, row R31 represents a set of signal intensities of the mass spectrum of the eluate introduced from the chromatograph 10 to the analyzer 20 at a first timing, and row R32 represents a set of signal intensities of the mass spectrum of the eluate introduced from the chromatograph 10 to the analyzer 20 at a second timing.

[0075] In matrix M30, each column represents the change over time in the signal intensity of a certain mass-to-charge ratio. For example, column C31 represents the change over time in the signal intensity of a component having a certain mass-to-charge ratio. More specifically, column C31 represents the change over time in the content of a component having a certain mass-to-charge ratio in the eluate introduced from chromatograph 10 to analyzer 20.

[0076] 7 shows another example of the relationship between the matrix expressions of a spectrum, a chromatogram vector, and a spectrum vector. While the example of FIG. 6 illustrates a case where a sample contains only one component, the example of FIG. 7 illustrates a case where a sample contains two or more components.

[0077] 7, line L11 represents a chromatogram of a sample containing only a first component among two or more types of components, and line L12 represents a chromatogram of a sample containing only a second component among two or more types of components.

[0078] 7, line L21 represents the spectrum of a sample containing only a first component among two or more types of components, and line L22 represents the spectrum of a sample containing only a second component among two or more types of components.

[0079] When a sample contains two or more types of components, the matrix M10 representing the chromatogram vectors includes two or more columns, as shown by columns C11 and C12, each corresponding to one of the two or more types. The matrix M20 representing the spectrum vectors includes two or more rows, as shown by rows R21 and R22, each corresponding to one of the two or more types.

[0080] 7, matrix M30 is the product of matrix M10 and matrix M20. For example, element F1 of matrix M30 is the sum of the product of row 1, column 1 of matrix M10 and row 1, column 1 of matrix M20, the product of row 1, column 2 of matrix M10 and row 2, column 1 of matrix M20, and so on.

[0081] In deconvolution, the relationship between such matrices M10, M20, and M30 is utilized to decompose a matrix corresponding to matrix M30 into a matrix corresponding to matrix M10 and a matrix corresponding to matrix M20.

[0082] More specifically, the analyzer 20 generates a spectrum for each eluate introduced from the chromatograph 10 at each of a plurality of timings for a given sample. The data processing device 100 generates a matrix equivalent to the matrix M30 using the spectra generated at the plurality of timings. The data processing device 100 then decomposes the generated matrix into a matrix of chromatogram vectors (equivalent to the matrix M10 in FIG. 7 ) and a matrix of spectral vectors (equivalent to the matrix M20 in FIG. 7 ).

[0083] There are an infinite number of ways to simply mathematically decompose a matrix. For example, according to prime factorization, if the value of an element of matrix M30 is 24, it can be decomposed into "2" and "12," "5" and "4.8," "-3" and "-8," and so on, resulting in an infinite number of possible combinations.

[0084] Therefore, in this embodiment, a constraint is imposed on the matrix decomposition such that the numerical values ​​of each column of the matrix M10 generated by the decomposition conform to an EMG distribution function (a function whose values ​​are positive and have a Gaussian shape), thereby enabling appropriate matrix decomposition of a matrix equivalent to the matrix M30.

[0085] For example, in matrix M30, the numerical values ​​in the first column (the leftmost column) change from 12 to 36 to 12, which is understood to represent one Gaussian shape. Note that if the numerical values ​​in a certain column in matrix M30 change from small to large to medium to large to small, the change in the numerical values ​​in this column is understood to correspond to two Gaussian shapes, and therefore, when matrix M30 has a column including such a change, matrix M30 is decomposed into a two-column chromatogram vector matrix (corresponding to matrix M10) and a two-row spectrum vector matrix (corresponding to matrix M20).

[0086] By carrying out the deconvolution described above, one or more peaks are extracted from the chromatogram.

[0087] The deconvolution method performed in the chromatography system 1 is not limited to the above-described method, but may be another method (for example, Gaussian peak fitting as described in Japanese Patent No. 6260709).

[0088] In the deconvolution described above, a mass spectrometer is used as an example of the analyzer 20, mass spectrometry is used as an example of the given analysis method, and mass spectrum is used as the "spectrum." Note that the given analysis method is not limited to this, and may be another analysis method, such as absorption spectrometry. When the given analysis method is absorption spectrometry, a fluorometer is used as an example of the analyzer 20, and a fluorescence spectrum is used as the "spectrum." In this case, "wavelength" is used instead of "mass-to-charge ratio" in Figures 4 and 5.

[0089] [Matching of Peaks] In one implementation example, matching of peaks in chromatogram G10 with peaks in chromatogram G20 utilizes the analysis results of the eluate of the portion corresponding to the peak in chromatogram G10 and the analysis results of the eluate of the portion corresponding to the peak in chromatogram G20 by analyzer 20. The analysis results of the eluate of the portion corresponding to the peak by analyzer 20 refer to the analysis results of analyzer 20 on the portion introduced into analyzer 20 when a certain portion of the eluate exhibits a certain peak in the chromatogram.

[0090] 8 is a diagram for explaining the correspondence of peaks. In FIG. 8, the analysis results of peaks P11, P12, P13, P14, P15, P16, and P17 in chromatogram G10 are shown as analysis results A11, A12, A13, A14, A15, A16, and A17, respectively. Also, the analysis results of peaks P21, P22, P23, P24, P25, P26, and P27 in chromatogram G20 are shown as analysis results A21, A22, A23, A24, A25, A26, and A27, respectively.

[0091] The data processing device 100 associates a peak in the chromatogram G10 with a peak in the chromatogram G20 whose analysis results match those of the peak.

[0092] For example, to identify a peak in chromatogram G20 that corresponds to peak P11, data processing device 100 searches for analysis results A21, A22, A23, A24, A25, A26, and A27 that match analysis result A11. If analysis result A11 matches analysis result A22, data processing device 100 associates peak P11 with peak P22 that corresponds to analysis result A22.

[0093] 8, pairs of matching analysis results are connected by dashed lines. More specifically, analysis results A11, A12, A13, A14, A15, A16, and A17 each match analysis results A22, A23, A21, A25, A26, A24, and A27, respectively. As a result, the data processing device 100 associates peaks P11, P12, P13, P14, P15, P16, and P17 with peaks P22, P23, P21, P25, P26, P24, and P27, respectively.

[0094] The type of value used as the analysis result depends on the type of device used as the analyzer 20. If the analyzer 20 is a mass spectrometer, the value used as the analysis result may be, for example, the mass-to-field ratio value and / or signal intensity of a peak in the mass spectrum. If the analyzer 20 is a fluorometer, the value used as the analysis result may be, for example, the wavelength, peak width, symmetry coefficient, and / or signal intensity of a peak in the fluorescence spectrum.

[0095] [Processing Flow] Figure 9 is a flowchart of processing performed by the data processing device 100 to associate peaks in multiple chromatograms. In one implementation example, the processing of Figure 9 is performed by the calculation device 101 executing a given program in the data processing device 100. In one implementation example, the data processing device 100 starts the processing of Figure 9 in response to receiving a command to start the association via the input unit 120.

[0096] In step S10, the data processing device 100 acquires the results of experiments performed on a sample under each of a plurality of different conditions. In one implementation, the results of each experiment are stored in the memory 102, and in step S10, the computing device 101 reads the results of the experiments stored in the memory 102.

[0097] The experimental results include chromatograms and analysis results. The experimental results performed under first conditions include the measurement results by chromatograph 10 under first column conditions (e.g., chromatogram G10) and the analysis results by analyzer 20 (e.g., analysis results A11 to A17 in FIG. 8 ). The experimental results performed under second conditions include the measurement results by chromatograph 10 under second column conditions (e.g., chromatogram G20) and the analysis results by analyzer 20 (e.g., analysis results A21 to A27 in FIG. 8 ). The column conditions include, for example, the type of mobile phase and / or the type of stationary phase.

[0098] In step S20, the data processing device 100 separates peaks in the chromatogram of the results of each experiment.

[0099] In step S30, the data processing device 100 performs correspondence between peaks in chromatograms among the results of a plurality of experiments.

[0100] In step S40, the data processing device 100 generates a result of the association performed in step S30. One example of the generated result is the chromatogram G30 (and chromatograms G10 and G20) shown in Fig. 2, and another example is the table shown in Fig. 3.

[0101] In step S50, the data processing device 100 displays the results generated in step S40 on the display unit 110. Thereafter, the data processing device 100 ends the processing of FIG.

[0102] [Example (1)] Fig. 10 is a diagram showing a first specific example of displaying the results of the association. Fig. 10 shows chromatograms 500, 510, and 520. Chromatogram 510 is a chromatogram obtained by measurement under first conditions. Chromatogram 520 is a chromatogram obtained by measurement under second conditions. Chromatogram 500 is a chromatogram generated by combining chromatograms 510 and 520.

[0103] The vertical axis of chromatogram 510 and the horizontal axis of chromatogram 520 represent retention time. The horizontal axis of chromatogram 510 and the vertical axis of chromatogram 520 represent signal intensity. The horizontal axis of chromatogram 500 represents retention time for the vertical axis and chromatogram 520, and the vertical axis of chromatogram 500 represents retention time for the chromatogram 510.

[0104] A group of peaks (peaks 511, 512, 513, and 514) is extracted from the chromatogram 510. A group of peaks (peaks 521, 522, 523, and 524) is extracted from the chromatogram 520.

[0105] 10 , peaks 512, 513, and 514 in chromatogram 510 correspond to peaks 522, 524, and 523 in chromatogram 520, respectively. Peak 511 in chromatogram 510 does not correspond to any peak in chromatogram 520. Furthermore, peak 521 in chromatogram 520 does not correspond to any peak in chromatogram 510.

[0106] Chromatogram 500 includes three peaks 501, 502, and 503. Peak 501 is formed by the product of the signal intensity of peak 512 in chromatogram 510 and the signal intensity of peak 522 in chromatogram 520. Peak 502 is formed by the product of the signal intensity of peak 513 in chromatogram 510 and the signal intensity of peak 524 in chromatogram 520. Peak 503 is formed by the product of the signal intensity of peak 514 in chromatogram 510 and the signal intensity of peak 523 in chromatogram 520. The shading of each of the three peaks 501, 502, and 503 depends on the value of the product that constitutes each peak. More specifically, the larger the product value of each peak, the higher the concentration displayed.

[0107] [Example (2)] Fig. 11 is a diagram showing a second specific example of displaying the results of the association. Fig. 11 shows chromatograms 600, 620, and 640. Chromatogram 620 is a chromatogram obtained by measurement under first conditions. Chromatogram 640 is a chromatogram obtained by measurement under second conditions. Chromatogram 600 is a chromatogram generated by combining chromatograms 620 and 640.

[0108] The vertical axis of chromatogram 620 and the horizontal axis of chromatogram 640 represent retention time. The horizontal axis of chromatogram 620 and the vertical axis of chromatogram 640 represent signal intensity. The horizontal axis of chromatogram 600 represents retention time for the vertical axis and chromatogram 640, and the vertical axis of chromatogram 600 represents retention time for the vertical axis and chromatogram 620.

[0109] A group of peaks (peaks 621 to 631) is extracted from chromatogram 620. A group of peaks (peaks 641 to 652) is extracted from chromatogram 640.

[0110] 12 is a diagram showing the correspondence between peaks in chromatogram 620 and peaks in chromatogram 640. As shown as "peaks in chromatogram 620" and "peaks in chromatogram 640" in the example of Fig. 12, peaks 622, 628, 626, 625, 627, 630, 621, 629, and 623 in chromatogram 620 correspond to peaks 642, 644, 645, 646, 627, 648, 650, 651, and 652 in chromatogram 640, respectively.

[0111] Chromatogram 600 includes peaks 601 to 609. Figure 12 shows the peaks in chromatograms 620 and 640 that make up each of peaks 601 to 609. For example, peak 601 is made up of peak 622 in chromatogram 620 and peak 642 in chromatogram 640.

[0112] The density of the image of each of peaks 601-609 is determined by the product of the signal intensity of the peak in chromatogram 620 and the signal intensity of the peak in chromatogram 640. For example, the density of the image shown as peak 601 is determined by the product of the signal intensity of peak 622 in chromatogram 620 and the signal intensity of peak 642 in chromatogram 640.

[0113] 11, the extracted peaks are close to each other in both chromatogram 620 and chromatogram 640. For example, in chromatogram 620, three peaks 627, 628, and 629 are close to each other. Also, in chromatogram 640, three peaks 650, 651, and 652 are close to each other.

[0114] According to this embodiment, a virtual two-dimensional chromatogram (chromatogram 600) is obtained by multiplying the signal intensities of corresponding peaks in two chromatograms 620 and 640 obtained under different conditions. In the virtual two-dimensional chromatogram (chromatogram 600), each peak is represented by the product of only the signal intensities of corresponding peaks in chromatograms 620 and 640, and does not include information about the signal intensities of other peaks in chromatograms 620 and 640. As a result, peaks 627, 628, and 629 and peaks 650, 651, and 652, which are close to each other in the original two chromatograms 620 and 640, are appropriately separated in chromatogram 600.

[0115] According to this embodiment, by performing measurements by the chromatograph 10 (and analysis by the analyzer 20) under just two different conditions, a chromatogram 600 can be obtained that separates peaks that were close to each other in the two chromatograms 620 and 640.

[0116] Aspects It will be understood by those skilled in the art that the exemplary embodiments described above are examples of the following aspects.

[0117] (Item 1) A data processing device according to one aspect is a data processing device that processes data, and includes an interface and an arithmetic unit that acquires, via the interface, a first chromatogram of a sample according to first conditions and a second chromatogram of the sample according to second conditions. The arithmetic unit may separate the first chromatogram into a first peak group, separate the second chromatogram into a second peak group, associate each of a plurality of peaks included in the first peak group with each of a plurality of peaks included in the second peak group, and display a result of the association.

[0118] According to the data processing device described in paragraph 1, it is possible to provide the user with information that enables detailed examination of the sample, and a technique for reducing the burden on the user is provided.

[0119] (Clause 2) In the data processing device described in paragraph 1, the calculation device may use, in the correspondence, analysis results of portions of the sample corresponding to each of the plurality of peaks included in the first peak group by an analysis method other than the first chromatogram, and analysis results of portions of the sample corresponding to each of the plurality of peaks included in the second peak group by an analysis method other than the second chromatogram.

[0120] According to the data processing device described in paragraph 2, the correspondence between the peaks included in the first chromatogram and the peaks included in the second chromatogram is based on the analysis results of the parts corresponding to these peaks that were used to obtain the respective chromatograms, thereby enabling accurate correspondence between the peaks.

[0121] (Clause 3) In the data processing device described in clause 2, the analysis method other than the first chromatogram and the analysis method other than the second chromatogram may be mass spectrometry or absorption spectrometry.

[0122] According to the data processing device described in paragraph 3, the correlation between peaks can be easily and accurately performed.

[0123] (4) In the data processing device described in any one of paragraphs 1 to 3, the calculation device may be configured such that the result includes a correspondence between peak information identifying each of the plurality of peaks included in the first peak group and peak information identifying each of the plurality of peaks included in the second peak group.

[0124] According to the data processing device described in paragraph 4, the user can easily understand the correspondence between the peaks extracted in each of the multiple chromatograms.

[0125] (5) In the data processing device according to 4, the peak information may represent an order of retention times in a chromatogram.

[0126] According to the data processing device described in paragraph 5, the user can more easily understand the correspondence between the peaks extracted in each of the multiple chromatograms.

[0127] (Clause 6) In the data processing device described in any one of clauses 1 to 5, the result may include a three-dimensional representation, in which a first dimension is the retention time of the first chromatogram, a second dimension is the retention time of the second chromatogram, and a third dimension is a value based on a signal intensity commonly used in the first chromatogram and the second chromatogram.

[0128] According to the data processing device described in paragraph 6, the user can obtain knowledge not only of the correspondence between the peaks in the first chromatogram and the peaks in the second chromatogram, but also of the signal intensities of both peaks.

[0129] (Clause 7) In the data processing device described in Clause 6, the first peak group may include a first peak, the second peak group may include a second peak, the correspondence may correspond the first peak to the second peak, and the three-dimensional representation may present values ​​based on intensity information representing the signal intensity of the first peak and the signal intensity of the second peak at an intersection of the retention time of the first peak on the first axis and the retention time of the second peak on the second axis on a plane formed by a first axis representing the retention time of the first chromatogram and a second axis representing the retention time of the second chromatogram.

[0130] According to the data processing device described in paragraph 7, the user can intuitively understand the relationship between a peak in the first chromatogram and the second chromatogram corresponding to that peak.

[0131] (Item 8) In the data processing device described in item 7, the intensity information may represent a product of the signal intensity of the first peak and the signal intensity of the second peak.

[0132] According to the data processing device described in paragraph 8, the user can highlight the signal intensity of the peak in the first chromatogram and the signal intensity of the peak in the second chromatogram in the intensity information.

[0133] (Clause 9) A data processing method according to one aspect may include the steps of separating a first chromatogram according to first conditions of a sample into a first peak group and separating a second chromatogram according to second conditions of the sample into a second peak group, associating each of the plurality of peaks included in the first peak group with each of the plurality of peaks included in the second peak group, and displaying a result of the association.

[0134] According to the data processing method described in paragraph 9, it is possible to provide the user with information that enables detailed examination of the sample, and a technique for reducing the burden on the user is provided.

[0135] (10th Clause) A program according to one aspect may cause a computer to carry out the method according to the 9th clause by being executed by an arithmetic unit of the computer.

[0136] According to the program described in paragraph 10, it is possible to provide the user with information that enables detailed examination of the sample, and a technique for reducing the burden on the user is provided.

[0137] (Clause 11) A chromatography system according to one aspect includes a data processing device and a chromatograph, wherein the data processing device includes an arithmetic device, and the arithmetic device may acquire from the chromatograph a first chromatogram according to first conditions of a sample and a second chromatogram according to second conditions of the sample, separate the first chromatogram into a first peak group, separate the second chromatogram into a second peak group, associate each of a plurality of peaks included in the first peak group with each of a plurality of peaks included in the second peak group, and display a result of the association.

[0138] According to the chromatography system described in item 11, it is possible to provide the user with information that enables detailed examination of the sample, and a technique for reducing the burden on the user is provided.

[0139] The embodiments disclosed herein should be considered to be illustrative in all respects and not restrictive. The scope of the present disclosure is defined by the claims, not by the description of the above-described embodiments, and is intended to include all modifications within the meaning and scope of the claims. Furthermore, it is intended that each technique in the embodiments can be implemented alone or, if necessary, in combination with other techniques in the embodiments to the extent possible.

[0140] 1 Chromatography system, 10 chromatograph, 14 column, 15 measuring device, 20 analyzer, 100 data processing device, 101 computing device, 500, 510, 520, 600, 620, 640, G10, G11, G20, G21, G30, GG21 chromatogram, M10, M20, M30 matrix.

Claims

1. A data processing device for processing data, The interface and a computing device that acquires, via the interface, a first chromatogram of the sample according to a first condition and a second chromatogram of the sample according to a second condition; The computing device separating the first chromatogram into a first group of peaks; separating the second chromatogram into a second set of peaks; Corresponding each of the plurality of peaks included in the first peak group to each of the plurality of peaks included in the second peak group; Displaying the results of the matching; The result includes a correspondence relationship between peak information identifying each of the plurality of peaks included in the first peak group and peak information identifying each of the plurality of peaks included in the second peak group.

2. 2. The data processing device according to claim 1, wherein, in the association, the calculation device utilizes analysis results of portions of the sample corresponding to each of the plurality of peaks included in the first peak group by an analysis method other than the first chromatogram, and analysis results of portions of the sample corresponding to each of the plurality of peaks included in the second peak group by an analysis method other than the second chromatogram.

3. The data processing apparatus according to claim 2 , wherein the analysis method other than the first chromatogram and the analysis method other than the second chromatogram are mass spectrometry or absorption spectrometry.

4. The data processing apparatus according to claim 1 , wherein the peak information represents an order with respect to retention time in a chromatogram.

5. the results include a three-dimensional representation; 2. The data processing device of claim 1, wherein in the three-dimensional representation, the first dimension is the retention time of the first chromatogram, the second dimension is the retention time of the second chromatogram, and the third dimension is a value based on signal intensity commonly used in the first chromatogram and the second chromatogram.

6. the first peak group includes a first peak, the second peak group includes a second peak, 6. The data processing device according to claim 5, wherein the correspondence corresponds the first peak to the second peak, and the three-dimensional representation presents a value based on intensity information representing the signal intensity of the first peak and the signal intensity of the second peak at an intersection of the retention time of the first peak on the first axis and the retention time of the second peak on the second axis in a plane formed by a first axis representing the retention time of the first chromatogram and a second axis representing the retention time of the second chromatogram.

7. 7. The data processing apparatus according to claim 6, wherein the value based on the intensity information is a product of the signal intensity of the first peak and the signal intensity of the second peak.

8. A data processing device for processing data, The interface and a computing device that acquires, via the interface, a first chromatogram of the sample according to a first condition and a second chromatogram of the sample according to a second condition; The computing device separating the first chromatogram into a first group of peaks; separating the second chromatogram into a second set of peaks; Corresponding each of the plurality of peaks included in the first peak group to each of the plurality of peaks included in the second peak group; Displaying the results of the matching; the results include a three-dimensional representation; A data processing device wherein in the three-dimensional representation, the first dimension is the retention time of the first chromatogram, the second dimension is the retention time of the second chromatogram, and the third dimension is a value based on signal intensity commonly used in the first chromatogram and the second chromatogram.

9. Separating a first chromatogram of the sample under first conditions into a first group of peaks and a second chromatogram of the sample under second conditions into a second group of peaks; performing a correspondence between each of the plurality of peaks included in the first peak group and each of the plurality of peaks included in the second peak group; and displaying the result of the association; A data processing method, wherein the result includes a correspondence relationship between peak information that identifies each of the plurality of peaks included in the first peak group and peak information that identifies each of the plurality of peaks included in the second peak group.

10. A step of separating a first chromatogram according to a first condition of a sample into a first group of peaks, and separating a second chromatogram according to a second condition of the sample into a second group of peaks; performing a correspondence between each of the plurality of peaks included in the first peak group and each of the plurality of peaks included in the second peak group; and displaying the result of the association; the results include a three-dimensional representation; A data processing method in which, in the three-dimensional representation, the first dimension is the retention time of the first chromatogram, the second dimension is the retention time of the second chromatogram, and the third dimension is a value based on signal intensity commonly used in the first chromatogram and the second chromatogram.