Peak Tracking Device, Peak Tracking Method, and Computer-Readable Medium

Abstract

The peak tracking device includes: a chromatography acquisition unit (203) that acquires a chromatogram (CG) based on measurement data (MD) obtained by providing analysis condition data (AP) to an analysis device (3); and a peak correspondence unit (205) that corresponds each peak included in each chromatogram. The peak correspondence unit includes: a peak spectrum extraction unit (206) that extracts a spectrum derived from a peak, i.e., peak spectrum data (PSD), from measurement spectrum data (MSD) obtained from each measurement data; an orthogonal spectrum extraction unit (207) that extracts spectrum data (RSD) orthogonal to a dominant component in the components of the peak spectrum data from the measurement spectrum data; and a similarity determination unit (208) that corresponds each peak based on the similarity of the spectrum data extracted by the orthogonal spectrum extraction unit.

Description

Technical Field

[0001] The present invention relates to a peak tracking device, a peak tracking method, and a non-transitory computer readable medium storing a peak tracking program. Background Art

[0002] It is possible to obtain a chromatogram of a sample based on measurement data acquired in an analysis device. Method Scouting is performed to optimize analysis condition data for the purpose of improving peak resolution or shortening analysis time.

[0003] When performing Method Scouting, it is necessary to perform peak tracking to identify peaks derived from the same substance among different chromatograms obtained based on different analysis condition data. To perform peak tracking, for example, the area value of a peak, the spectrum of a peak, or the similarity of the MS spectrum of a peak is used.

[0004] In addition, after performing peak tracking, a process for estimating a baseline is performed to extract true peaks from the chromatogram. Patent Document 1 below discloses a method for obtaining a peak chromatogram by removing the influence of the estimated baseline from the chromatogram.

[0005] Patent Document 1: International Publication No. 2017-119086 Summary of the Invention

[0006] Problems to be Solved by the Invention

[0007] It is known that in the synthesis of pharmaceuticals with relatively large molecular weights such as nucleic acid pharmaceuticals and peptide pharmaceuticals, analogs with similar structures are generated as by-products. Since the spectra of such analogs are also similar, peak tracking may not be fully performed even using spectral similarity. In addition, the MS spectra of such analogs are mostly similar in shape, and a large amount of labor is required to search for m / z values that output a specific chromatogram for each peak. Even by using the method of peak area values, in most cases, the combination cannot be completely locked, and peak tracking may not be fully performed.

[0008] In addition, depending on specific analysis condition data, the peaks of two components may accidentally overlap. In this case, peak tracking may not be fully performed simply using a method that only determines similarity such as a correlation function.

[0009] An object of the present invention is to provide an effective method for identifying peaks included in a chromatogram.

[0010] Solutions to the Problems

[0011] The peak tracking device according to one aspect of the present invention includes: a chromatography acquisition unit that acquires a plurality of chromatograms based on a plurality of measurement data obtained by providing a plurality of analysis condition data to an analysis device; and a peak correspondence unit that corresponds each peak included in each chromatogram. The peak correspondence unit includes: a peak spectrum extraction unit that extracts a spectrum derived from a peak, i.e., peak spectrum data, from measurement spectrum data obtained from each measurement data; an orthogonal spectrum extraction unit that extracts spectrum data orthogonal to a dominant component in the components of the peak spectrum data from the measurement spectrum data; and a similarity determination unit that performs correspondence of each peak based on the similarity of the spectrum data extracted by the orthogonal spectrum extraction unit.

[0012] Effect of the invention

[0013] According to the present invention, an effective method for identifying peaks included in a chromatogram can be provided. Brief description of the drawings

[0014] Figure 1 is an overall view of the analysis system according to this embodiment.

[0015] Figure 2 is a structural diagram of the computer according to this embodiment.

[0016] Figure 3 is a functional block diagram of the computer according to this embodiment.

[0017] Figure 4 is a functional block diagram showing the structure of the peak spectrum extraction unit.

[0018] Figure 5 is a diagram showing measurement spectrum data and a chromatogram.

[0019] Figure 6 is a diagram showing chromatograms obtained according to different analysis condition data.

[0020] Figure 7 is a flowchart showing the peak tracking method according to this embodiment.

[0021] Figure 8 is a diagram obtained by superimposing chromatograms of each wavelength of the orthogonal spectrum data extracted by the orthogonal spectrum extraction unit.

[0022] Figure 9 is a diagram obtained by superimposing chromatograms of each wavelength of the orthogonal spectrum data extracted by the orthogonal spectrum extraction unit.

[0023] Figure 10 is a diagram obtained by superimposing chromatograms of each wavelength of the orthogonal spectrum data extracted by the orthogonal spectrum extraction unit.

[0024] Figure 11It is a graph obtained by superimposing the chromatograms of each wavelength of the orthogonal spectrum data extracted by the orthogonal spectrum extraction unit.

[0025] Figure 12 It is a graph obtained by superimposing the chromatograms of each wavelength of the orthogonal spectrum data extracted by the orthogonal spectrum extraction unit. Detailed implementation manners

[0026] Next, with reference to the accompanying drawings, the structures of the peak tracking device, method, and program according to the embodiments of the present invention will be described.

[0027] (1) Overall structure of the analysis system

[0028] Figure 1 It is the overall diagram of the analysis system 5 according to this embodiment. The analysis system 5 includes a computer 1 and a liquid chromatograph 3. The computer 1 is connected to the liquid chromatograph 3 via a network 4. The network 4 is, for example, a LAN (Local Area Network).

[0029] The computer 1 has functions such as setting analysis conditions for the liquid chromatograph 3 and obtaining and analyzing the measurement results of the liquid chromatograph 3. A program for controlling the liquid chromatograph 3 is installed in the computer 1.

[0030] The liquid chromatograph 3 includes a pump unit, an autosampler unit, a column oven unit, a detector unit, etc. As the detector, for example, a photodiode array (PDA), a mass spectrometer (MS), etc. are used. The liquid chromatograph 3 also includes a system controller. The system controller controls the liquid chromatograph 3 according to the control instructions received from the computer 1 via the network 4. The system controller sends the data of the measurement results of the liquid chromatograph 3 to the computer 1 via the network 4.

[0031] (2) Structure of the computer (peak tracking device)

[0032] Figure 2 It is the structure diagram of the computer 1. Regarding the computer 1, a personal computer is used in this embodiment. The computer 1 includes a CPU (Central Processing Unit) 101, a RAM (Random Access Memory) 102, a ROM (Read Only Memory) 103, a display 104, an operation unit 105, a storage device 106, a communication interface 107, and a device interface 108.

[0033] The CPU 101 controls the computer 1. The RAM 102 is used as a work area when the CPU 101 executes programs. Control programs and the like are stored in the ROM 103. The display 104 is, for example, a liquid crystal display. The operation unit 105 is a device that accepts user operations and includes a keyboard, a mouse, etc. It is also possible that the display 104 is composed of a touch panel display, and the display 104 has the function of the operation unit 105. The storage device 106 is a device that stores various programs and data. The storage device 106 is, for example, a hard disk. The communication interface 107 is an interface for communicating with other computers and devices. The communication interface 107 is connected to the network 4. The device interface 108 is an interface for accessing various external devices. The CPU 101 can access the storage medium 109 via an external device connected to the device interface 108.

[0034] Stored in the storage device 106 are a peak tracking program P1, analysis condition data AP, measurement data MD, measurement spectrum data MSD, chromatogram CG, peak spectrum data PSD, baseline spectrum data BSD, and orthogonal spectrum data RSD. The peak tracking program P1 is a program for controlling the liquid chromatograph 3. The peak tracking program P1 has functions such as setting analysis conditions for the liquid chromatograph 3, obtaining measurement results from the liquid chromatograph 3, and analyzing the measurement results such as generating a chromatogram CG, etc.

[0035] The analysis condition data AP is data that describes the analysis conditions set for the liquid chromatograph 3 and contains multiple analysis parameters. The measurement data MD is data of the measurement results obtained from the liquid chromatograph 3 based on the analysis condition data AP. The measurement data MD is a three-dimensional chromatogram having three dimensions composed of time, wavelength, and absorbance (signal intensity). The measurement spectrum data MSD is absorbance data in the wavelength direction extracted from the measurement data MD, which is a three-dimensional chromatogram, for a specific measurement time. The chromatogram CG is absorbance data in the time direction extracted from the measurement data MD, which is a three-dimensional chromatogram, for a specific wavelength.

[0036] The peak spectrum data PSD is data obtained by extracting spectral components originating from peaks in the measurement spectrum data MSD. The baseline spectrum data BSD is data obtained by extracting spectral components originating from the baseline in the measurement spectrum data MSD. The orthogonal spectrum data RSD is spectral data extracted from the measurement spectrum data MSD and is a component orthogonal to the dominant component in the components of the peak spectrum data PSD.

[0037] Figure 3 It is a functional block diagram of the computer 1. The control unit 200 is a functional unit implemented by the CPU 101 using the RAM 102 as a work area to execute the peak tracking program P1. The control unit 200 includes an analysis management unit 201, a chromatogram acquisition unit 203, a spectrum acquisition unit 204, a peak correspondence unit 205, and a spectrum display unit 210.

[0038] The Analysis Management Unit 201 controls the liquid chromatograph 3. The Analysis Management Unit 201 receives an instruction from the user to start setting analysis condition data AP and performing analysis processing, and thus gives an instruction to the liquid chromatograph 3 to perform analysis processing. The user sets a combination of set values of analysis parameters such as solvent concentration, solvent mixing ratio, gradient initial value, gradient slope, and column temperature as analysis conditions. The user sets multiple such combinations of analysis parameters. For example, a combination of analysis parameters obtained by gradually changing the solvent concentration and a combination of analysis parameters obtained by gradually changing the column temperature are set as analysis conditions. The user creates multiple analysis condition data AP in this way and performs analysis processing on the same sample based on the multiple analysis condition data AP.

[0039] In addition, the Analysis Management Unit 201 obtains measurement data MD as three-dimensional chromatography from the liquid chromatograph 3. As described above, the user performs analysis processing based on multiple analysis condition data AP. The Analysis Management Unit 201 obtains multiple measurement data MD corresponding to the multiple analysis condition data AP.

[0040] The Chromatogram Acquisition Unit 203 obtains a chromatogram CG based on the measurement data MD. The Chromatogram Acquisition Unit 203 stores the obtained chromatogram CG in the storage device 106. As described above, the Analysis Management Unit 201 obtains multiple measurement data MD corresponding to the multiple analysis condition data AP. The Chromatogram Acquisition Unit 203 obtains multiple chromatograms CG corresponding to the multiple measurement data MD.

[0041] The Spectrum Acquisition Unit 204 obtains measurement spectrum data MSD based on the measurement data MD. The Spectrum Acquisition Unit 204 stores the obtained measurement spectrum data MSD in the storage device 106.

[0042] The Peak Corresponding Unit 205 performs peak correspondence between multiple chromatograms obtained based on different analysis condition data AP. As shown in the figure, the Peak Corresponding Unit 205 includes a Peak Spectrum Extraction Unit 206, an Orthogonal Spectrum Extraction Unit 207, a Similarity Determination Unit 208, and a Baseline Spectrum Extraction Unit 209.

[0043] The Peak Spectrum Extraction Unit 206 extracts peak spectrum data PSD as spectrum components derived from peaks from the measurement spectrum data MSD. The Orthogonal Spectrum Extraction Unit 207 extracts orthogonal spectrum data RSD from the measurement spectrum data MSD. The orthogonal spectrum data RSD is data obtained by extracting components orthogonal to the dominant components in the components of the peak spectrum data PSD from the measurement spectrum data MSD. In addition, the orthogonal spectrum data RSD is data obtained by extracting components orthogonal to the baseline spectrum data BSD from the measurement spectrum data MSD. The Similarity Determination Unit 208 determines the similarity of the peaks included in the multiple chromatograms CG based on the orthogonal spectrum data RSD. The Baseline Spectrum Extraction Unit 209 extracts baseline spectrum data BSD, which is a component derived from the baseline, from the measurement spectrum data MSD.

[0044] The spectrum display unit 210 displays the orthogonally reduced spectrum data RSD on the display 104. Specifically, the spectrum display unit 210 displays on the display 104 a graph obtained by superimposing the chromatograms of each wavelength of the orthogonally reduced spectrum data RSD extracted by the orthogonal spectrum extraction unit 207.

[0045] Figure 4 is a functional block diagram of the peak spectrum extraction unit 206. The peak spectrum extraction unit 206 includes a peak region determination unit 211, a baseline estimation unit 212, and a baseline removal unit 213. The peak region determination unit 211 determines the peak start point and the peak end point in the retention time direction of the peak in the chromatogram CG. The baseline estimation unit 212 estimates the baseline component in the chromatogram CG. The baseline removal unit 213 removes the baseline component from the measurement spectrum data MSD.

[0046] Figure 5 is a graph showing the measurement data MD. As described above, the measurement data MD is three-dimensional chromatographic data with time, wavelength, and absorbance (signal intensity) as three axes. As shown in the figure, by fixing the measurement time in the measurement data MD, the measurement spectrum data MSD can be extracted. A plurality of measurement spectrum data MSD are extracted in the time direction. For the plurality of measurement spectrum data MSD in the time direction, by fixing the wavelength, the chromatogram CG can be extracted. The illustrated chromatogram CG represents the chromatogram CG at the wavelength λ0. The peak in the chromatogram CG has a width in the time direction from the peak start point Ts to the peak end point Te.

[0047] Figure 6 is a graph showing two chromatograms CG1 and CG2 obtained based on two different analysis condition data AP. The chromatograms CG1 and CG2 are obtained based on the measurement data MD obtained for the same sample. As is known with reference to Figure 6 , in the chromatograms CG1 and CG2, the retention times of the respective peaks are different due to the difference in the analysis condition data AP. The peaks connected by a dotted line in the figure are peaks derived from the same substance. The peak correspondence unit 205 performs the correspondence of the peaks included in the chromatograms CG1 and CG2.

[0048] (3) Peak tracking method

[0049] Next, the peak tracking method executed in the computer 1 (peak tracking device) according to the present embodiment will be described. Figure 7 is a flowchart showing the peak tracking method according to the present embodiment.

[0050] Before starting the Figure 7 shown processing, the user pre-operations the operation unit 105 to set a plurality of analysis conditions. The analysis management unit 201 accepts such a setting operation by the user and stores the plurality of analysis condition data AP in the storage device 106.

[0051] Then, in Figure 7 In step S101 shown, the analysis management unit 201 sets a plurality of analysis condition data AP for the liquid chromatograph 3. Specifically, the analysis management unit 201 sets a plurality of analysis condition data AP for the system controller of the liquid chromatograph 3. Accordingly, in the liquid chromatograph 3, a plurality of analysis processes are performed on the same sample based on the set plurality of analysis condition data AP. In the liquid chromatograph 3, a plurality of measurement data MD are acquired corresponding to the plurality of analysis condition data AP.

[0052] Next, in step S102, the analysis management unit 201 acquires a plurality of measurement data MD from the liquid chromatograph 3. The analysis management unit 201 stores the acquired plurality of measurement data MD in the storage device 106.

[0053] Next, in step S103 , the chromatogram acquisition unit 203 acquires the plurality of measurement data MD stored in the storage device 106 in step S102 , and acquires a plurality of chromatograms CG from the acquired plurality of measurement data MD.

[0054] Next, in step S104, the peak spectrum extractor 206 extracts the peak spectrum data PSD, which is the spectrum derived from the peak, from the measured spectrum data MSD. The extraction process of the peak spectrum data PSD includes three processes: peak region identification process, baseline estimation process, and baseline removal process.

[0055] first, Figure 4 The peak region determination unit 211 shown performs peak region determination processing. The peak region determination unit 211 applies a second-order differential filter (Savitzky-Golay) to the chromatogram CG, and the second-order differential filter has a length of about half-value width in the time direction as the window width. Most of the baselines contained in the chromatogram CG can be approximated by formulas up to the first order, so most of the baselines can be eliminated by second-order differentials. Thus, the peak region determination unit 211 can determine the peak region. It can also be that the peak region is determined by using a high-pass filter, a matched filter, or a time-invariant filter / transformation such as a wavelet transform by utilizing the fact that the frequency of change of the peak region is higher than the frequency of change of the baseline in most cases. Even in the case where a filter process is implemented in the time direction like this, as long as the filter performs linear processing, it will not affect the space itself formed by the vector extension (Japanese: Zhang ru) of the spectrum originating from each peak. Alternatively, it is also possible to use a peak detection algorithm such as Labsol and specify the peak start point and peak end point by the user.

[0056] then, Figure 4The baseline estimation unit 212 shown performs baseline estimation processing. The baseline estimation unit 212 estimates the baseline by linearly interpolating between the peak start point and the peak end point determined by the peak region determination unit 211 in the retention time direction. That is, the baseline is estimated by linearly interpolating the peak bottom points. Alternatively, when it is predicted that the baseline is a curve, the baseline is estimated by curve interpolation between the peak start point and the peak end point determined by the peak region determination unit 211 in the retention time direction. That is, the baseline is estimated by curve interpolating the peak bottom points.

[0057] Finally, Figure 4 The baseline removal unit 213 shown performs baseline removal processing. The baseline removal unit 213 subtracts the signal value of the baseline from the signal value of the measurement spectrum data MSD based on the baseline estimated by the baseline estimation unit 212. For example, if it is a peak vertex, the signal value of the baseline at the peak vertex position where linear interpolation has been performed is subtracted from the signal value of the measurement spectrum data MSD. At this time, in order not to damage the spectrum, the same signal value is subtracted at each wavelength of the measurement spectrum data MSD (each m / z in the case of the detector being MS).

[0058] Through the above processing, the peak spectrum extraction unit 206 extracts the peak spectrum data PSD by removing the baseline spectrum data BSD from the measurement spectrum data MSD. The peak spectrum extraction unit 206 further performs factorization such as singular value decomposition (principal component analysis) on the peak spectrum data PSD. In the present embodiment, according to the empirically determined threshold of the singular value, the spectral components are locked as the main components. As long as the original vector space can be represented, other factorizations such as spectral analysis can also be used. The peak spectrum extraction unit 206 stores the extracted peak spectrum data PSD in the storage device 106.

[0059] Next, in step S105, the baseline spectrum extraction unit 209 extracts the spectrum derived from the baseline, that is, the baseline spectrum data BSD, from the measurement spectrum data MSD. In the present embodiment, the baseline spectrum extraction unit 209 extracts the baseline spectrum data BSD by using the Savitzky-Golay filter as a low-pass filter. As a method for extracting the baseline spectrum data BSD, other linear filters can also be used. In addition, the baseline spectrum extraction unit 209 may also extract the baseline spectrum data BSD by linearly or curve interpolating the peak start point and the peak end point to remove the peak portion. Alternatively, after removing the peak portion, a low-pass filter may be applied to extract the baseline spectrum data BSD. The baseline spectrum extraction unit 209 further performs factorization such as singular value decomposition on the baseline spectrum data BSD.

[0060] The above processing is a method of extracting baseline spectrum data BSD by performing signal processing on measurement spectrum data MSD. As another method, it is also possible to obtain measurement spectrum data MSD only from the mobile phase or pretreatment chemicals without injecting the sample to be analyzed, and thereby extract baseline spectrum data BSD.

[0061] Through the above processing, three types of data, namely measurement spectrum data MSD, peak spectrum data PSD, and baseline spectrum data BSD, are obtained. Regarding the peak tracking program P1 of the present embodiment, through the processing shown below, the vector components that contribute to peak tracking in these three types of data are retained while other components are reduced.

[0062] First, in step S106, the orthogonal spectrum extraction unit 207 extracts the component orthogonal to the baseline spectrum data BSD from the measurement spectrum data MSD. This orthogonalization process is set as the first orthogonalization process. This process is an orthogonalization process aimed at removing the hyperplane component extended from the baseline spectrum data BSD. Therefore, it is also possible to orthogonalize the measurement spectrum data MSD with all factors (all spectra) of the baseline spectrum data BSD obtained by factorization.

[0063] Next, in step S107, the orthogonal spectrum extraction unit 207 performs a second orthogonalization process on the measurement spectrum data MSD that has been subjected to the first orthogonalization process in step S106. In the second orthogonalization process, the orthogonal spectrum extraction unit 207 extracts the component orthogonal to the dominant component in the components of the peak spectrum data PSD from the measurement spectrum data MSD. The components extracted through the first orthogonalization process and the second orthogonalization process are orthogonal spectrum data RSD. The dominant component in the peak spectrum data PSD is, for example, the spectrum that becomes the first principal component in the spectrum obtained by singular value decomposition (principal component analysis). Alternatively, as the dominant component, the average value in the time direction of the peak spectrum data PSD can also be used. In addition, since both the orthogonalization process in step S106 and the orthogonalization process in step S107 are linear processes, the order of these processes can be either one first.

[0064] Then, in step S108, the similarity determination unit 208 performs correspondence of each peak based on the similarity of the orthogonal spectrum data RSD. The similarity determination unit 208, for example, determines the similarity of each peak based on the correlation of the extracted orthogonal spectrum data RSD for multiple peaks obtained from different chromatograms CG. The similarity determination unit 208 corresponds the peaks whose correlation exceeds a specified threshold to each other as peaks derived from the same substance.

[0065] Thus, in the present embodiment, the peak corresponding unit 205 includes a peak spectrum extraction unit 206, an orthogonal spectrum extraction unit 207, and a similarity determination unit 208. Among them, the peak spectrum extraction unit 206 extracts peak spectrum data PSD from the measurement spectrum data MSD obtained from the measurement data MD, the orthogonal spectrum extraction unit 207 extracts orthogonal spectrum data RSD orthogonal to the main component in the components of the peak spectrum data PSD from the measurement spectrum data MSD, and the similarity determination unit 208 performs correspondence of each peak based on the similarity of the orthogonal spectrum data RSD. Thus, the computer 1 as the peak tracking device in the present embodiment can remove the main components common in the time direction and determine the similarity of the peaks based on the components orthogonal to the main components.

[0066] In addition, in the above processing, the orthogonal spectrum data RSD is extracted by performing the first orthogonalization process and the second orthogonalization process, thereby more effectively performing peak identification. However, the first orthogonalization process is not essential. In particular, in the case where the influence of baseline variation such as gradient elution is small, the orthogonalization based on the baseline spectrum data BSD can be omitted.

[0067] Figures 8 - 12 It is a diagram showing an example of the orthogonal spectrum data RSD extracted by the orthogonal spectrum extraction unit 207. Figure 8 of (A), Figure 9 of (A), Figure 10 of (A), Figure 11 of (A) is a diagram obtained by superimposing the chromatograms at each wavelength of the orthogonal spectrum data RSD extracted by the orthogonal spectrum extraction unit 207. Figure 8 of (B), Figure 9 of (B), Figure 10 of (B), Figure 11 of (B) is for Figure 8 of (A), Figure 9 of (A), Figure 10 of (A), Figure 11 of (A) is a diagram after dimensionality reduction of the orthogonal spectrum data RSD.

[0068] Figure 8 and Figure 9 show the orthogonal spectrum data RSD related to the peaks derived from the same substance. When referring to Figure 8 of (A) and Figure 9 of (A), although the shapes of the peaks are relatively similar, it is difficult to determine whether the peaks are derived from the same substance. However, when referring to Figure 8 of (B) and Figure 9 of (B) after dimensionality reduction, it is known that the possibility that the peaks are derived from the same substance is very high. In Figure 8 of (B) and Figure 9In (B) thereof, the chromatograms of the orthogonal spectral data RSD are depicted with different line types for each wavelength. When referring to Figure 8 (B) of Figure 9 and (B) of

[0069] Figure 10 and Figure 11 it is known that the chromatograms for each wavelength are arranged in the same order. Figure 10 (A) of Figure 11 and (A) of Figure 10 When referring to (B) of Figure 11 and (B) of Figure 10 (B) of Figure 11 it is known that the orthogonal spectral data RSD related to the peaks derived from different substances are shown. Although the shapes of the peaks are relatively similar, it is difficult to determine whether the peaks are derived from the same substance. However, when referring to (B) of Figure 10 and (B) of Figure 11 after dimensionality reduction, it is known that the possibility that the peaks are derived from different substances is very high. In (B) of

[0070] and (B) of

[0071] Figure 3 the spectral display unit 210 shown in Figure 8 (B) of Figure 9 (B) of Figure 10 (B) of Figure 11 (B) of

[0072] (4) Correspondence between the constituent elements of the claims and the elements of the embodiments

[0073] Next, examples of the correspondence between the constituent elements of the claims and the elements of the embodiments will be described, but the present invention is not limited to the following examples. In the above-described embodiment, the liquid chromatograph 3 is an example of the analysis device. Further, in the above-described embodiment, the computer 1 is an example of the peak tracking device.

[0074] As the constituent elements of the claims, various elements having the structures or functions described in the claims can also be used.

[0075] (5) Other Embodiments

[0076] (5-1) Omission of Orthogonalization of Peak Spectrum Dominant Components

[0077] In the above-described embodiment, the orthogonal spectrum extraction unit 207 extracts orthogonal spectrum data RSD through the first orthogonal process and the second orthogonal process. Here, when the method of cutting out the peak region is used to estimate the baseline spectrum data BSD, sometimes minute peak spectrum components are mixed into the baseline spectrum data BSD. In this case, by orthogonalizing the measurement spectrum data MSD using the baseline spectrum data BSD, orthogonalization of the dominant components of the peak spectrum data PSD is also performed. In such a case, by performing only the first orthogonal process, the same effect as the case of performing both the first orthogonal process and the second orthogonal process can be presented. Therefore, if the peak similarity is below a fixed threshold determined empirically, orthogonalization using the dominant components of the peak spectrum can also be omitted.

[0078] (5-2) Presentation of Peak Mixing Possibility

[0079] According to specific analysis condition data AP, sometimes two peaks derived from different substances are accidentally superimposed and output as one peak. The peak tracking method of the present embodiment can also provide information for determining the mixing possibility for the mixed peak. If the spectrum SC of peak C formed by mixing peak A (spectrum SA) and peak B (spectrum SB) is completely superimposed, then SC = SA + SB. Even in the case of incomplete coincidence, SC is expressed as SC = αSA + βSB, and SC should converge to the space extended from spectra SA and SB.

[0080] In order to confirm the relationship such as SC = SA + SB, it is only necessary to confirm whether the sum of the integral values of the orthogonal spectrum data RSD in the region of peak A and the integral value of the orthogonal spectrum data RSD in the region of peak B converges within the error range of the value of SC. Thereby, information on the peak mixing possibility can be obtained.

[0081] Figure 12 It is a diagram showing an example of the orthogonal spectrum data RSD extracted by the orthogonal spectrum extraction unit 207. Figure 12The figure of (A) is obtained by superimposing the chromatograms at each wavelength of the orthogonal spectrum data RSD extracted by the orthogonal spectrum extraction unit 207. Figure 12 The figure of (B) is Figure 12 The figure after dimensionality reduction of the orthogonal spectrum data RSD of (A). When referring to Figure 12 the figure of (A), it also looks like a single peak. However, when referring to Figure 12 the figure of (B), it is known that there are peaks A and B that are slightly offset. Regarding the shape of the peaks, whether it is peak A included in peak C or the independent peak A, they are substantially the same. Therefore, it is also possible that if the chromatogram of the orthogonal spectrum data RSD of peak A is moved along the time direction to be superimposed on the chromatogram of peak B and the amount of movement is optimized, it can be confirmed to be consistent with the chromatogram of peak C. Although a large amount of computational effort is required in such a confirmation process, it can reduce the possibility of misjudging the peaks as being consistent.

[0082] The computer 1 can also output information related to the possibility of peak mixing to other devices, other programs, processes, etc. For example, it can also output information on the possibility of peak mixing to a device that performs processing for the purpose of AQBD (Analytical Quality by Design). In this case, in addition to having the Figure 2 function blocks shown, the control unit 200 of the computer 1 also has an output unit.

[0083] For example, there is a program or device that obtains the design space of retention time and resolution by performing regression analysis on the retention time and resolution of peaks. It is also possible to output the information on the possibility of peak mixing calculated in the present embodiment to these programs or devices for processing the design space. For example, in a device that has input the information on the possibility of peak mixing, the information can be presented in a manner that correlates the design space with the possibility of peak mixing.

[0084] (5-3) Other device structures

[0085] In the above embodiment, the liquid chromatograph 3 is taken as an example to illustrate the analytical device of the present invention. In addition to this, the present invention can also be applied to a gas chromatograph. Further, in the above embodiment, the case where the computer 1 as the peak tracking device is connected to the liquid chromatograph 3 as the analytical device via the network 4 is taken as an example for illustration. As another embodiment, the computer 1 can also be structured to be built into the analytical device. Additionally, in the above embodiment, the case where the measurement spectrum data MSD is spectrum data having signals such as absorbance at each wavelength is taken as an example for illustration. In addition to this, the present invention can also be applied to spectrum data having signal values at each m / z by using MS as a detector.

[0086] (5-4) Method for providing a program

[0087] In the above-described embodiment, the case where the peak tracking program P1 is stored in the storage device 106 has been described as an example. As another embodiment, the peak tracking program P1 may also be provided by being stored in the storage medium 109. The CPU 101 may also access the storage medium 109 via the device interface 108, and store the peak tracking program P1 stored in the storage medium 109 in the storage device 106 or the ROM 103. Alternatively, the CPU 101 may access the storage medium 109 via the device interface 108 to execute the peak tracking program P1 stored in the storage medium 109.

[0088] Furthermore, the specific structure of the present invention is not limited to the above-described embodiment, and various changes and modifications can be made without departing from the gist of the invention.

[0089] (6) Mode

[0090] Those skilled in the art can understand that the above-described multiple exemplary embodiments are specific examples of the following modes.

[0091] (First item)

[0092] The peak tracking device according to one mode of the present invention includes:

[0093] a chromatogram acquisition unit that acquires a plurality of chromatograms based on a plurality of measurement data obtained by providing a plurality of analysis condition data to an analysis device; and

[0094] a peak correspondence unit that corresponds each peak included in each chromatogram,

[0095] wherein the peak correspondence unit includes:

[0096] a peak spectrum extraction unit that extracts a spectrum originating from a peak, i.e., peak spectrum data, from measurement spectrum data obtained from each measurement data;

[0097] an orthogonal spectrum extraction unit that extracts spectrum data orthogonal to a dominant component in the components of the peak spectrum data from the measurement spectrum data; and

[0098] a similarity determination unit that corresponds each peak based on the similarity of the spectrum data extracted by the orthogonal spectrum extraction unit.

[0099] According to the peak tracking device of the first item, the peaks included in the chromatogram can be identified.

[0100] (Second item)

[0101] In the peak tracking device according to the first item, it may also be that

[0102] The peak corresponding part includes a baseline spectrum extraction part, and the baseline spectrum extraction part extracts the spectrum originating from the baseline, i.e., baseline spectrum data, from the measurement spectrum data obtained according to each measurement data.

[0103] The orthogonal spectrum extraction part extracts the spectrum data orthogonal to the baseline spectrum data from each measurement spectrum data.

[0104] It is possible to effectively identify peaks by excluding the influence of baseline variation components.

[0105] (The third item)

[0106] In the peak tracking device described in the first or second item, it may also be that

[0107] The peak spectrum extraction part includes:

[0108] A peak region determination part that determines the peak region by applying a second-order differential filter or a high-pass filter to each chromatogram;

[0109] A baseline estimation part that estimates the baseline based on the determined peak region; and

[0110] A baseline removal part that removes the baseline from the measurement spectrum data.

[0111] By removing the baseline, it is possible to exclude the influence of baseline variation components.

[0112] (The fourth item)

[0113] In the peak tracking device described in any one of the first to third items, it may also be that

[0114] The orthogonal spectrum extraction part obtains the principal component by performing singular value decomposition of the peak spectrum data.

[0115] It is possible to obtain the principal component of the peak spectrum data by singular value decomposition. Thus, the peak tracking device can effectively identify peaks using the components other than the principal component in the peak spectrum data.

[0116] (The fifth item)

[0117] In the peak tracking device described in any one of the first to third items, it may also be that

[0118] The orthogonal spectrum extraction part obtains the principal component according to the average value in the time direction of the peak spectrum data.

[0119] It is possible to obtain the principal component of the peak spectrum data according to the average value. Thus, the peak tracking device can effectively identify peaks using the components other than the principal component in the peak spectrum data.

[0120] (The sixth item)

[0121] In the peak tracking device according to any one of the first to fifth items, it may also be that

[0122] It further includes a spectrum display unit that reduces the dimension of the spectrum data extracted by the orthogonal spectrum extraction unit and displays it on a display.

[0123] The user can visually confirm the propriety of the peak similarity determination performed by the peak tracking device.

[0124] (Seventh item)

[0125] In the peak tracking device according to any one of the first to sixth items, it may also be that

[0126] Information indicating that the spectrum data extracted by the orthogonal spectrum extraction unit is included in a hyperplane extended from the spectrum data of multiple substances is provided as information on the possibility of peak mixing.

[0127] The possibility of peak mixing can be provided to the user.

[0128] (Eighth item) The peak tracking device according to another aspect of the present invention includes:

[0129] A chromatogram acquisition unit that acquires a plurality of chromatograms based on a plurality of measurement data obtained by providing a plurality of analysis condition data to an analysis device; and

[0130] A peak correspondence unit that corresponds each peak included in each chromatogram,

[0131] wherein the peak correspondence unit includes:

[0132] A baseline spectrum extraction unit that extracts a spectrum originating from the baseline, i.e., baseline spectrum data, from the measurement spectrum data obtained according to each measurement data;

[0133] An orthogonal spectrum extraction unit that extracts spectrum data orthogonal to the baseline spectrum data from each measurement spectrum data; and

[0134] A similarity determination unit that corresponds each peak according to the similarity of the spectrum data extracted by the orthogonal spectrum extraction unit.

[0135] Peak identification can be performed by excluding components orthogonal to the baseline.

[0136] (Ninth item)

[0137] The peak tracking method according to another aspect of the present invention includes the following steps:

[0138] A chromatogram acquisition step of acquiring a plurality of chromatograms based on a plurality of measurement data obtained by providing a plurality of analysis condition data to an analysis device; and

[0139] Peak corresponding process, corresponding each peak included in each chromatogram.

[0140] Among them, the peak corresponding process includes the following processes:

[0141] Peak spectrum extraction process, extracting the spectrum originating from the peak, i.e., peak spectrum data, from the measurement spectrum data obtained based on each measurement data.

[0142] Orthogonal spectrum extraction process, extracting the spectrum data orthogonal to the dominant component in the components of the peak spectrum data from the measurement spectrum data; and

[0143] Similarity determination process, corresponding each peak according to the similarity of the orthogonal spectrum data extracted in the orthogonal spectrum extraction process.

[0144] According to the peak tracking method of item 9, the peaks included in the chromatogram can be identified.

[0145] (Item 10)

[0146] In a computer-readable medium (Non-transitory computer readable medium) storing a peak tracking program according to another aspect of the present invention, the peak tracking program is used to cause a computer to execute the following processing:

[0147] Obtaining a plurality of chromatograms based on a plurality of measurement data obtained by providing a plurality of analysis condition data to an analysis device; and

[0148] Extracting the spectrum originating from the peak, i.e., peak spectrum data, from the measurement spectrum data obtained based on each measurement data, extracting the spectrum data orthogonal to the dominant component in the components of the peak spectrum data from the measurement spectrum data, and corresponding each peak according to the similarity of the extracted orthogonal spectrum data, thereby corresponding each peak included in each chromatogram.

[0149] According to the peak tracking program of item 10, the peaks included in the chromatogram can be identified.

Claims

1. A peak tracking device, comprising: A chromatogram acquisition unit that acquires a plurality of chromatograms based on a plurality of measurement data obtained by providing a plurality of analysis condition data to an analysis device; and a peak corresponding unit that corresponds each peak included in each chromatogram, wherein the peak corresponding unit includes: a peak spectrum extraction unit that extracts a spectrum originating from a peak, i.e., peak spectrum data, from measurement spectrum data obtained from each measurement data; an orthogonal spectrum extraction unit that extracts spectrum data orthogonal to the spectrum of the first principal component obtained by performing singular value decomposition on the peak spectrum data, or the average spectrum in the time direction of the peak spectrum data, from the measurement spectrum data; and a similarity determination unit that performs correspondence of each peak based on the similarity of the spectrum data extracted by the orthogonal spectrum extraction unit.

2. The peak tracking device according to claim 1, wherein the peak corresponding unit includes a baseline spectrum extraction unit that extracts a spectrum originating from a baseline, i.e., baseline spectrum data, from measurement spectrum data obtained from each measurement data, and the orthogonal spectrum extraction unit extracts spectrum data orthogonal to the baseline spectrum data from each measurement spectrum data.

3. The peak tracking device according to claim 1, wherein the peak spectrum extraction unit includes: a peak region determination unit that determines a peak region by applying a second-order differential filter or a high-pass filter to each chromatogram; a baseline estimation unit that estimates a baseline based on the determined peak region; and a baseline removal unit that removes the baseline from the measurement spectrum data.

4. The peak tracking device according to claim 1, wherein it further includes a spectrum display unit that displays the spectrum data extracted by the orthogonal spectrum extraction unit on a display after dimensionality reduction.

5. The peak tracking device according to claim 1, wherein information indicating that the spectrum data extracted by the orthogonal spectrum extraction unit is included in a hyperplane extended from spectrum data of multiple substances is provided as information on the mixing possibility of peaks.

6. A peak tracking device, comprising: A chromatogram acquisition unit that acquires a plurality of chromatograms based on a plurality of measurement data obtained by providing a plurality of analysis condition data to an analysis device; and a peak corresponding unit that corresponds each peak included in each chromatogram, wherein the peak corresponding unit includes: a baseline spectrum extraction unit that extracts a spectrum originating from a baseline, i.e., baseline spectrum data, from measurement spectrum data obtained from each measurement data; an orthogonal spectrum extraction unit that extracts spectrum data orthogonal to the baseline spectrum data from each measurement spectrum data; and a similarity determination unit that performs correspondence of each peak based on the similarity of the spectrum data extracted by the orthogonal spectrum extraction unit.

7. A peak tracking method, including the following steps: a chromatogram acquisition step of acquiring a plurality of chromatograms based on a plurality of measurement data obtained by providing a plurality of analysis condition data to an analysis device; and a peak correspondence step of corresponding each peak included in each chromatogram, wherein the peak correspondence step includes the following steps: a peak spectrum extraction step of extracting a spectrum originating from a peak, i.e., peak spectrum data, from measurement spectrum data obtained from each measurement data; an orthogonal spectrum extraction step of extracting spectrum data orthogonal to the spectrum of the first principal component obtained by performing singular value decomposition on the peak spectrum data, or the average spectrum in the time direction of the peak spectrum data, from the measurement spectrum data; and Similarity determination process, corresponding each peak according to the similarity of the orthogonal spectral data extracted in the orthogonal spectrum extraction process.

8. A computer-readable medium storing a peak tracking program, the peak tracking program causing a computer to execute the following processes: Obtaining a plurality of chromatograms based on a plurality of measurement data obtained by providing a plurality of analysis condition data to an analysis device; and Extracting spectral data originating from peaks, i.e., peak spectral data, from the measurement spectral data obtained according to each measurement data, extracting spectral data orthogonal to the spectrum of the first principal component obtained by performing singular value decomposition on the peak spectral data, or the average spectrum in the time direction of the peak spectral data, from the measurement spectral data, and corresponding each peak according to the similarity of the extracted orthogonal spectral data, thereby corresponding each peak included in each chromatogram.

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