Chromatogram waveform processing device and chromatogram waveform processing method

Abstract

To provide a chromatogram waveform processor generating a chromatogram that allows an accurate analysis, and a chromatogram waveform processing method.SOLUTION: A sample chromatogram acquisition part 1 acquires a sample chromatogram generated by measuring a moving phase where a sample is injected. Background chromatogram generated by measuring a moving phase that no sample is injected or a moving phase where a control sample is injected is acquired by a background chromatogram acquisition part 2. By aligning base lines of the acquired sample chromatogram and the acquired background chromatogram, the sample chromatogram and the background chromatogram are aligned by an alignment process part 3. Subtraction processing of the background chromatogram is performed by a subtraction processing part 4 from the aligned sample chromatogram.SELECTED DRAWING: Figure 4

Description

[Technical field]

[0001] The present invention relates to a chromatogram waveform processing device and a chromatogram waveform processing method. [Background technology]

[0002] Liquid chromatographs are known as devices that separate substances contained in a sample into different components. For example, Patent Document 1 describes an analyzer using high performance liquid chromatography. In this analyzer, a specimen to be analyzed is supplied as a sample to an analytical column together with an eluent. The sample introduced into the analytical column is eluted into individual components and then detected by a detector. Based on the detection results by the detector, a chromatogram is created that shows the relationship between the retention time and detection intensity of the sample components.

[0003] A chromatogram shows baseline fluctuations caused by background. If the baseline fluctuations are large, the analysis results may be inaccurate. Therefore, in Patent Document 1, a reference chromatogram is measured in which background data can be confirmed. The background data, which has been subjected to a predetermined correction, is subtracted from the chromatogram of the sample, thereby eliminating the baseline fluctuations. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] JP 2017-187319 A Summary of the Invention [Problem to be solved by the invention]

[0005] Since there is a deviation between the chromatogram of the sample and the reference chromatogram, the analytical results may be inaccurate even when the subtracted chromatogram is used.

[0006] An object of the present invention is to provide a chromatogram waveform processing device and a chromatogram waveform processing method that generate a chromatogram that enables accurate analysis. [Means for solving the problem]

[0007] One aspect of the present invention relates to a chromatogram waveform processing device comprising: a sample chromatogram acquisition unit that acquires a sample chromatogram generated by measuring a mobile phase into which a sample is injected; a background chromatogram acquisition unit that acquires a background chromatogram generated by measuring a mobile phase into which no sample is injected or a mobile phase into which a control sample is injected; an alignment processing unit that aligns the sample chromatogram and the background chromatogram by aligning the baselines of the sample chromatogram acquired by the sample chromatogram acquisition unit and the background chromatogram acquired by the background chromatogram acquisition unit; and a subtraction processing unit that subtracts the background chromatogram from the sample chromatogram after alignment by the alignment processing unit.

[0008] Another aspect of the present invention relates to a waveform processing method for a chromatogram, comprising the steps of acquiring a sample chromatogram generated by measuring a mobile phase into which a sample is injected, acquiring a background chromatogram generated by measuring a mobile phase into which no sample is injected or a mobile phase into which a control sample is injected, aligning the sample chromatogram and the background chromatogram by aligning the baselines of the acquired sample chromatogram and the acquired background chromatogram, and subtracting the background chromatogram from the aligned sample chromatogram. Effect of the Invention

[0009] According to the present invention, a chromatogram can be generated that allows for accurate analysis. [Brief description of the drawings]

[0010] [Figure 1] 1 is a diagram showing a configuration of an analysis system including a chromatogram waveform processing device according to a first embodiment of the present invention. [Diagram 2] FIG. 2 is a diagram illustrating an example of the mass spectrometer of FIG. [Diagram 3] FIG. 1 shows an example of a background chromatogram. [Figure 4] FIG. 1 shows an example of a sample chromatogram. [Diagram 5] FIG. 2 is a diagram illustrating a configuration of a waveform processing device. [Figure 6] FIG. 2 shows sample chromatograms in an example. [Figure 7] FIG. 1 shows a background chromatogram in an example. [Figure 8] FIG. 13 shows a sample chromatogram and a background chromatogram after alignment in an example. [Figure 9] FIG. 13 shows a sample chromatogram and a background chromatogram after alignment in the first reference example. [Figure 10] FIG. 13 shows a sample chromatogram and a background chromatogram after alignment in the second reference example. [Figure 11] FIG. 13 shows a sample chromatogram after subtraction processing in an example. [Figure 12] FIG. 13 shows a sample chromatogram after substitution in an example. [Figure 13] FIG. 6 is a diagram showing a sample chromatogram presented by the presentation unit of FIG. 5. [Figure 14] 6 is a flowchart showing waveform processing by the waveform processing device of FIG. 5; [Figure 15] FIG. 11 is a diagram showing an example of an analysis device according to a second embodiment of the present invention. [Figure 16] FIG. 16 is a schematic diagram showing the configuration of the detector in FIG. 15. [Figure 17]FIG. 1 shows an example of a background chromatogram. [Figure 18] FIG. 2 is a diagram illustrating a configuration of a waveform processing device. [Figure 19] 20 is a flowchart showing waveform processing by the waveform processing device of FIG. 18. [Figure 20] FIG. 13 is a diagram showing an example of an analysis device according to a third embodiment of the present invention. [Figure 21] FIG. 2 shows an example of a sample chromatogram and a background chromatogram. [Figure 22] FIG. 2 is a diagram illustrating a configuration of a waveform processing device. [Figure 23] 23 is a flowchart showing waveform processing by the waveform processing device of FIG. 22. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] [1] First embodiment (1) Analysis system configuration Hereinafter, a chromatogram waveform processing device and a chromatogram waveform processing method according to an embodiment of the present invention will be described in detail with reference to the drawings. Fig. 1 is a diagram showing a configuration of an analysis system including a chromatogram waveform processing device according to a first embodiment of the present invention. As shown in Fig. 1, an analysis system 300 includes a control device 100 and an analysis device 200.

[0012] The control device 100 is composed of a CPU (Central Processing Unit) 110, a RAM (Random Access Memory) 120, a ROM (Read Only Memory) 130, a storage unit 140, an operation unit 150, a display unit 160, and an input / output I / F (Interface) 170. The CPU 110, the RAM 120, the ROM 130, the storage unit 140, the operation unit 150, the display unit 160, and the input / output I / F 170 are connected to a bus 180. The CPU 110, the RAM 120, and the ROM 130 constitute a chromatogram waveform processing device 10 (hereinafter abbreviated as waveform processing device 10).

[0013] The RAM 120 is used as a working area for the CPU 110. The ROM 130 stores a system program. The storage unit 140 includes a storage medium such as a hard disk or a semiconductor memory. The storage unit 140 stores a waveform processing program for performing waveform processing on a chromatogram. The waveform processing program may be stored in the ROM 130 or an external storage device. The CPU 110 executes the waveform processing program stored in the storage unit 140 or the like on the RAM 120, thereby performing waveform processing on the chromatogram.

[0014] The operation unit 150 is an input device such as a keyboard, a mouse, or a touch panel, and is operated by a user to give predetermined instructions to the waveform processing device 10. The display unit 160 is a display device such as a liquid crystal display device, and displays a chromatogram that has been waveform processed by the waveform processing device 10. The input / output I / F 170 is connected to the analysis device 200.

[0015] The analytical device 200 may include, for example, a liquid chromatograph or a liquid chromatograph mass spectrometer using an eluent as a mobile phase. The analytical device 200 may also include a gas chromatograph or a gas chromatograph mass spectrometer using a carrier gas as a mobile phase. Alternatively, the analytical device 200 may include a supercritical fluid chromatograph or a supercritical fluid chromatograph mass spectrometer using a supercritical fluid as a mobile phase.

[0016] Fig. 2 is a diagram showing an example of the mass spectrometer 200 of Fig. 1. As shown in Fig. 2, the mass spectrometer 200 is a liquid chromatograph, and includes a storage unit 210, a mobile phase supply unit 220, a sample supply unit 230, a separation column 240, a detector 250, and a processing unit 260. The storage unit 210 includes, for example, a chemical bottle, and stores an eluent such as an aqueous solution or an organic solvent as a mobile phase.

[0017] The mobile phase supplying unit 220 includes, for example, a liquid delivery pump, and pressure-feeds the mobile phase stored in the storage unit 210. The sample supplying unit 230 includes, for example, an auto-injector, and introduces the sample to be analyzed together with the mobile phase supplied by the mobile phase supplying unit 220 into the separation column 240. The separation column 240 is housed inside a column thermostatic bath (not shown) and is adjusted to a predetermined constant temperature. The separation column 240 separates the introduced sample into components based on differences in chemical properties or composition.

[0018] The detector 250 includes, for example, a UV (ultraviolet) detector, and detects components of the sample separated by the separation column 240. The processing unit 260 controls the operations of the mobile phase supply unit 220, the sample supply unit 230, the separation column 240 (column thermostatic bath), and the detector 250. The processing unit 260 also processes the detection results by the detector 250 to generate a chromatogram showing the relationship between the retention time and detection intensity of each component.

[0019] The analytical device 200 generates a chromatogram (hereinafter referred to as a background chromatogram) by measuring the mobile phase into which no sample is injected. Fig. 3 is a diagram showing an example of a background chromatogram. As shown in Fig. 3, the background chromatogram shows pseudo peaks p1 and p2 of 0 or more (2 in the example of Fig. 3) that are not caused by the sample, as well as baseline fluctuations. The pseudo peaks are caused by injection shock, the mobile phase, gradient conditions, impurity components, etc.

[0020] Moreover, the analysis device 200 generates a chromatogram (hereinafter referred to as a sample chromatogram) by measuring the mobile phase into which the sample to be analyzed is injected. Fig. 4 is a diagram showing an example of a sample chromatogram. As shown in Fig. 4, the sample chromatogram shows one or more peaks Q (1 in the example of Fig. 4) caused by the sample in addition to pseudo peaks P1 and P2 similar to the above pseudo peaks p1 and p2, respectively, and baseline fluctuations.

[0021] The analytical device 200 provides the generated background chromatogram and sample chromatogram to the control device 100. Note that the background chromatogram may be generated before the generation of the sample chromatogram, or may be generated during the generation of multiple sample chromatograms by batch processing.

[0022] (2) Waveform processing device Fig. 5 is a diagram showing the configuration of the waveform processing device 10. As shown in Fig. 5, the waveform processing device 10 includes, as functional units, a sample chromatogram acquisition unit 1, a background chromatogram acquisition unit 2, an alignment processing unit 3, a subtraction processing unit 4, a replacement unit 5, an identification unit 6, and a presentation unit 7. The functional units of the waveform processing device 10 are realized by the CPU 110 in Fig. 1 executing a waveform processing program stored in the storage unit 140 or the like. Some or all of the functional units of the waveform processing device 10 may be realized by hardware such as electronic circuits.

[0023] The sample chromatogram acquisition unit 1 acquires a sample chromatogram from the analysis device 200. The background chromatogram acquisition unit 2 acquires a background chromatogram from the analysis device 200. The alignment processing unit 3 aligns the baselines of the sample chromatogram acquired by the sample chromatogram acquisition unit 1 and the background chromatogram acquired by the background chromatogram acquisition unit 2 so that the shapes of the peaks or drifts match. In this way, the sample chromatogram and the background chromatogram are aligned.

[0024] In this example, the alignment processing unit 3 includes a distance cost calculation unit 3a, a time alignment unit 3b, a search unit 3c, and an intensity alignment unit 3d, and aligns the baseline by estimating the positions of peaks (including pseudo peaks) in the sample chromatogram and the background chromatogram. The distance cost calculation unit 3a calculates the distance cost between the sample chromatogram and the background chromatogram using a dynamic time warping (DTW) method.

[0025] Specifically, the distance cost calculation unit 3a determines one or more points in the background chromatogram that provisionally correspond to each of the multiple points in the sample chromatogram as provisional corresponding points. One point in the sample chromatogram may correspond to multiple adjacent provisional corresponding points in the background chromatogram. Alternatively, multiple adjacent points in the sample chromatogram may correspond to one provisional corresponding point in the background chromatogram.

[0026] In addition, the distance cost calculation unit 3a calculates the distance between each point of the sample chromatogram and the provisional corresponding point of the background chromatogram, and calculates the sum of the distances calculated for the multiple points of the sample chromatogram as the distance cost. Here, if the distance included in the distance cost exceeds a predetermined upper limit, the distance cost calculation unit 3a presumes that the point of the sample chromatogram that is the start point of the distance or the provisional corresponding point of the background chromatogram that is the end point of the distance is a peak, and calculates the distance cost by setting the distance to a constant value.

[0027] The upper limit of the distance is, for example, twice the amount of noise in the analysis device 200 that generates the sample chromatogram and the background chromatogram. In calculating the distance cost, the distance cost calculation unit 3a may estimate the amount of noise from the background chromatogram using Gaussian process regression, or may estimate the amount of noise from a known device accuracy error of the analysis device 200. As described above, by setting the distance exceeding the upper limit to a constant value, it is possible to calculate the distance cost in a state where peaks due to the sample and pseudo peaks included in only one of the sample chromatogram and the background chromatogram are excluded.

[0028] The time alignment unit 3b updates the tentative corresponding points of the background chromatogram for each point of the sample chromatogram. The time alignment unit 3b also determines the tentative corresponding points that have the smallest distance cost as the confirmed corresponding points. In this way, alignment in the time direction is performed based on each point of the sample chromatogram and the confirmed corresponding points of the background chromatogram.

[0029] When the baseline shift between the sample chromatogram and the background chromatogram in the intensity direction is large, most distances exceed the upper limit, making it impossible to calculate a reasonable distance cost. Therefore, the search unit 3c adds a modification function to the background chromatogram to modify the background chromatogram. The modification function is given by, for example, the following formula (1). In formula (1), t is time, and a and b are the direct current component and the time gradient in the background chromatogram, respectively.

[0030]

number

[0031] The search unit 3c searches for values ​​of parameters a and b in the modification function g(t) so as to reduce the variation of the baseline of the background chromatogram relative to the baseline of the sample chromatogram. The value of parameter b may be 0. The modification function g(t) is not limited to formula (1) and may include a nonlinear term. The intensity alignment unit 3d performs intensity alignment between the sample chromatogram and the background chromatogram to which the modification function g(t) has been added.

[0032] The subtraction processing unit 4 subtracts the background chromatogram from the sample chromatogram after alignment by the alignment processing unit 3. The subtraction processing unit 4 may display the sample chromatogram after subtraction processing on the display unit 160. In response to an instruction from the user, the replacement unit 5 replaces parts of the sample chromatogram having a predetermined intensity or less with 0 in the sample chromatogram after subtraction processing by the subtraction processing unit 4. The predetermined intensity may be, for example, twice the amount of noise in the analysis device 200. The user can instruct the above replacement by operating the operation unit 150.

[0033] The identification unit 6 identifies peaks originating from the sample based on the sample chromatogram that has been subjected to subtraction processing by the subtraction processing unit 4. The presentation unit 7 causes the display unit 160 to visually display the peaks originating from the sample based on the identification result by the identification unit 6 in the sample chromatogram before the subtraction processing is performed.

[0034] (3) Examples Fig. 6 is a diagram showing a sample chromatogram in the embodiment. The sample chromatogram in Fig. 6 is acquired by the sample chromatogram acquisition unit 1 in Fig. 5. As shown in Fig. 6, the sample chromatogram in the embodiment shows two pseudo peaks P1, P2 and 16 peaks Q1 to Q16, as well as baseline fluctuations.

[0035] Fig. 7 is a diagram showing a background chromatogram in the embodiment. The background chromatogram in Fig. 7 is acquired by the background chromatogram acquisition unit 2 in Fig. 5. As shown in Fig. 7, the background chromatogram in the embodiment shows two pseudo peaks p1 and p2, as well as baseline fluctuations.

[0036] Fig. 8 shows a sample chromatogram and a background chromatogram after alignment in an embodiment. In Fig. 8 and Figs. 9 and 10 described below, the sample chromatogram is shown by a dotted line. In the alignment by the alignment processing unit 3 in Fig. 5, the positions of peaks Q1 to Q16 are estimated as described above. Furthermore, the distance cost is calculated with the estimated peaks Q1 to Q16 excluded.

[0037] The sample chromatogram in Fig. 6 and the background chromatogram in Fig. 7 are associated with each other so that the calculated distance cost is minimized. As a result, as shown in Fig. 8, the sample chromatogram and the background chromatogram are aligned so that the positions of the pseudo peaks P1 and P2 and the positions of the pseudo peaks p1 and p2 are aligned, and the baselines are aligned with each other.

[0038] FIG. 9 shows a sample chromatogram and a background chromatogram after alignment in the first reference example. In the first reference example, peaks Q1 to Q16 are not removed, and a modified function g(t) is added to the background chromatogram. In this case, as shown in FIG. 9, the position of pseudo-peak p1 is aligned with the position of pseudo-peak P1, but the position of pseudo-peak p2 is aligned with the positions of peaks Q2 and Q3, not with the position of pseudo-peak P2. This results in inaccurate alignment between the sample chromatogram and the background chromatogram.

[0039] Fig. 10 is a diagram showing a sample chromatogram and a background chromatogram after alignment in the second reference example. Depending on the number of searches for tentative corresponding points in the background chromatogram, the presence of a local solution may cause alignment to be performed in a state where the position of a pseudo peak in the background chromatogram is aligned with the position of a non-corresponding peak in the sample chromatogram. In the second reference example, as shown in Fig. 10, alignment is performed in a state where the position of the pseudo peak p2 is aligned with the position of the non-corresponding peak Q1.

[0040] Therefore, in the calculation of the distance cost, the distance cost calculation unit 3a in Fig. 5 may replace the distance cost including the distance between any point in the sample chromatogram and a tentative corresponding point in the background chromatogram with infinity if the point is shifted from the tentative corresponding point in the background chromatogram by a predetermined time or more. This prevents alignment from being performed in a state where the position of a pseudo peak in the background chromatogram is aligned with the position of a non-corresponding peak in the sample chromatogram.

[0041] Alternatively, instead of replacing the distance cost with infinity, the distance cost calculation unit 3a may increase the distance cost according to the magnitude of the time shift between an arbitrary point in the sample chromatogram and a tentative corresponding point in the background chromatogram. For example, a cost C shown in the following formula (2) may be added to the distance cost. In formula (2), t1 is the time of the arbitrary point in the sample chromatogram, and t2 is the time of the tentative corresponding point in the background chromatogram.

[0042]

number

[0043] Fig. 11 shows a sample chromatogram after subtraction processing in the embodiment. The background chromatogram is subtracted from the sample chromatogram in Fig. 8 by the subtraction processing unit 4 in Fig. 5. This removes the pseudo peaks P1 and P2 and baseline fluctuations from the sample chromatogram, as shown in Fig. 11. As a result, only peaks Q1 to Q16 attributable to the sample remain in the sample chromatogram.

[0044] Fig. 12 is a diagram showing a sample chromatogram after replacement in the embodiment. If the user wishes to remove noise from the sample chromatogram of Fig. 11 that has been subjected to subtraction processing, the user issues a replacement instruction by operating the operation unit 150 of Fig. 5. In this case, as shown in Fig. 12, in the sample chromatogram, parts that are below a predetermined intensity are replaced with 0 by the replacement unit 5 of Fig. 5. This allows the user to observe the sample chromatogram from which noise has been removed.

[0045] FIG. 13 is a diagram showing a sample chromatogram presented by the presentation unit 7 in FIG. 5. As shown in FIG. 13, the sample chromatogram before the subtraction process is performed is presented by the presentation unit 7. In this sample chromatogram, peaks derived from the sample identified by the identification unit 6 in FIG. 5 based on the sample chromatogram after the subtraction process are displayed so as to be visibly recognized. In the example of FIG. 13, the start and end positions of each peak are indicated by arrows. This allows the user to easily recognize the peaks derived from the sample in the original sample chromatogram.

[0046] (4) Waveform processing Fig. 14 is a flowchart showing waveform processing by the waveform processing device 10 of Fig. 5. The waveform processing of Fig. 14 is performed by the CPU 110 of Fig. 1 executing a waveform processing program stored in the ROM 130 or the storage unit 140, etc., on the RAM 120. The waveform processing will be described below with reference to the waveform processing device 10 of Fig. 5 and the flowchart of Fig. 14.

[0047] First, the sample chromatogram acquisition unit 1 acquires a sample chromatogram from the analysis device 200 (step S1). The background chromatogram acquisition unit 2 acquires a background chromatogram from the analysis device 200 (step S2). Steps S1 and S2 may be performed either first or simultaneously.

[0048] Next, the search unit 3c transforms the background chromatogram acquired in step S2 using the transformation function g(t) (step S3). Then, the intensity alignment unit 3d performs intensity direction alignment between the sample chromatogram acquired in step S1 and the background chromatogram transformed in step S3 (step S4).

[0049] Thereafter, the distance cost calculation unit 3a calculates the distance cost by determining the tentative corresponding points in the background chromatogram (step S5). Here, the time alignment unit 3b judges whether the distance cost is minimum or not (step S6). If the distance cost is not minimum, the alignment processing unit 3 updates the search conditions (step S7) and returns to step S3. The update of the search conditions includes at least one of updating the tentative corresponding points by the time alignment unit 3b and updating the parameters of the transformation function g(t) by the search unit 3c.

[0050] Steps S3 to S7 are repeated until the distance cost is minimized. The number of times the search is repeated may be determined in advance. When the distance cost is minimized, the time alignment unit 3b performs alignment in the time direction between the sample chromatogram and the background chromatogram by determining a definite corresponding point in the background chromatogram (step S8).

[0051] Next, the subtraction processing unit 4 subtracts the background chromatogram from the sample chromatogram after alignment in step S8 (step S9). The replacement unit 5 then determines whether or not a user has instructed replacement (step S10). If replacement has not been instructed, the replacement unit 5 proceeds to step S12. If replacement has been instructed, the replacement unit 5 replaces parts of the sample chromatogram that have been subjected to the subtraction processing in step S9 that have an intensity lower than a predetermined value with 0 (step S11), and proceeds to step S12.

[0052] In step S12, the identifying unit 6 identifies peaks derived from the sample based on the sample chromatogram subjected to subtraction processing in step S9 or the sample chromatogram subjected to substitution processing in step S11 (step S12). Finally, the presenting unit 7 causes the display unit 160 to display the original sample chromatogram obtained in step S1 so that the peaks identified in step S12 are visible (step S13), and ends the waveform processing.

[0053] (5) Effects In the waveform processing device 10 according to this embodiment, the sample chromatogram and the background chromatogram are aligned by the alignment processing unit 3 so that the baselines are aligned. In this state, the subtraction processing unit 4 subtracts the background chromatogram from the sample chromatogram, so that the sample chromatogram contains almost no peaks or baseline fluctuations that are not attributable to the sample. This makes it possible to generate a chromatogram that enables accurate analysis.

[0054] In the alignment, the distance cost calculation unit 3a determines one or more tentative corresponding points in the background chromatogram, and calculates the sum of the distances between each point of the sample chromatogram and the tentative corresponding points in the background chromatogram as the distance cost. The time alignment unit 3b updates the tentative corresponding points in the background chromatogram, and performs alignment in the time direction based on the tentative corresponding points that minimize the distance cost and each point of the sample chromatogram.

[0055] Here, if the distance included in the calculated distance cost exceeds a predetermined upper limit, the distance is set to a constant value and the distance cost is calculated. In this case, the distance cost is calculated in a state where peaks due to the sample and pseudo peaks included only in either the sample chromatogram or the background chromatogram are excluded. This allows accurate alignment of the sample chromatogram and the background chromatogram.

[0056] In addition, in the calculation of the distance cost, a modification function g(t) that modifies the background chromatogram so as to reduce the variation of the baseline of the background chromatogram relative to the baseline of the sample chromatogram is searched for by the search unit 3c. The intensity alignment unit 3d performs intensity alignment between the sample chromatogram and the background chromatogram to which the modification function g(t) searched for by the search unit 3c has been applied.

[0057] This configuration allows the sample chromatogram and the background chromatogram to be more accurately associated with each other even when the baselines of the sample chromatogram and the background chromatogram are significantly offset in the intensity direction, thereby generating a chromatogram that enables more accurate analysis.

[0058] [2] Second embodiment (1) Configuration of the analytical device Regarding the chromatogram waveform processing device and chromatogram waveform processing method according to the second embodiment, differences from the waveform processing device 10 according to the first embodiment will be described. FIG. 15 is a diagram showing an example of an analysis device 200 according to the second embodiment of the present invention. As shown in FIG. 15, the mass analysis device 200 further includes a switching unit 270 and a detector 280. The switching unit 270 includes, for example, a flow path switching valve. The switching unit 270 selectively guides the mobile phase that has passed through the separation column 240 to the detector 250 or the detector 280 by switching the downstream flow path.

[0059] Fig. 16 is a schematic diagram showing the configuration of detector 280 in Fig. 15. As shown in Fig. 16, detector 280 includes a flow cell 281, a light projecting unit 282, a spectroscopic unit 283, and a light receiving unit 284. Flow cell 281 has a main body unit 281a in which an inlet 281b, a flow path 281c, and an outlet 281d are formed.

[0060] 15 is introduced into the inside of the main body 281a from the inlet 281b as shown by the arrow a. The mobile phase then flows in one direction through the flow path 281c inside the main body 281a as shown by the arrow b. The mobile phase then flows out of the main body 281a from the outlet 281d as shown by the arrow c.

[0061] The light projection unit 11 includes a light source that emits broadband light, such as a deuterium lamp, and irradiates the mobile phase flowing through the flow path 281c of the flow cell 281 with light. The light irradiated to the mobile phase interacts with the mobile phase, then passes through the mobile phase and is incident on the spectroscopic unit 12. The spectroscopic unit 12 is, for example, a reflective diffraction grating, and disperses the incident light so as to reflect it at different angles for each wavelength. The light receiving unit 13 includes a PDA (photodiode array) in which multiple photodiodes are arranged in a one-dimensional manner. The light receiving unit 13 receives the light of each wavelength dispersed by the spectroscopic unit 12, and outputs a signal indicating the amount of received light to the processing unit 260 in FIG. 15.

[0062] The processing unit 260 further controls the operations of the switching unit 270 and the detector 280. The processing unit 260 also generates a chromatogram by processing the detection result by the detector 280. In this embodiment, the switching unit 270 is controlled so that the mobile phase is led to the detector 250 when the sample chromatogram is generated, and the mobile phase is led to the detector 280 when the background chromatogram is generated. Therefore, the sample chromatogram is a two-dimensional chromatogram showing the relationship between the retention time and detection intensity of each component. On the other hand, the background chromatogram is a three-dimensional chromatogram showing the relationship between the retention time and detection intensity of each component and the detection wavelength of the detector 280.

[0063] Fig. 17 is a diagram showing an example of a background chromatogram. In the upper part of Fig. 17, a three-dimensional background chromatogram is shown by contour lines. In the three-dimensional background chromatogram, the horizontal axis indicates time, the vertical axis indicates wavelength, and color indicates intensity. By selecting an arbitrary wavelength from the three-dimensional background chromatogram, it is possible to display a two-dimensional background chromatogram as shown in the lower part of Fig. 17.

[0064] (2) Waveform processing device Fig. 18 is a diagram showing the configuration of the waveform processing device 10. As shown in Fig. 18, the waveform processing device 10 further includes a wavelength selection unit 8 as a functional unit. The operations of the sample chromatogram acquisition unit 1, the alignment processing unit 3, the subtraction processing unit 4, the replacement unit 5, the identification unit 6 and the presentation unit 7 are similar to those in the first embodiment.

[0065] The background chromatogram acquisition unit 2 acquires a three-dimensional background chromatogram from the analysis device 200. In addition, the background chromatogram acquisition unit 2 acquires a two-dimensional selected background chromatogram corresponding to the wavelength selected by the wavelength selection unit 8 from the acquired three-dimensional background chromatogram.

[0066] The wavelength selection unit 8 selects any one of the wavelengths in the three-dimensional background chromatogram in response to an instruction from the user. The user can specify a wavelength at which a pseudo peak or baseline fluctuation appears appropriately in the three-dimensional background chromatogram by operating the operation unit 150. Alternatively, the wavelength selection unit 8 may select a wavelength at which a pseudo peak or baseline fluctuation appears more appropriately from a predetermined range of wavelengths including the wavelength specified by the user. Alternatively, the wavelength selection unit 8 may automatically select a wavelength at which a pseudo peak or baseline fluctuation appears appropriately.

[0067] (3) Waveform processing Fig. 19 is a flowchart showing waveform processing by the waveform processing device 10 of Fig. 18. In the waveform processing of Fig. 19, steps S2a, S2b, and S2c are executed in sequence instead of step S2 in the waveform processing of Fig. 14.

[0068] Specifically, the sample chromatogram acquisition unit 1 acquires a sample chromatogram from the analysis device 200 (step S1). The sample chromatogram is a two-dimensional chromatogram. The background chromatogram acquisition unit 2 acquires a three-dimensional background chromatogram from the analysis device 200 (step S2a). The wavelength selection unit 8 selects one of the wavelengths in the three-dimensional background chromatogram acquired in step S2a (step S2b).

[0069] The background chromatogram acquisition unit 2 acquires a two-dimensional selected background chromatogram based on the three-dimensional background chromatogram acquired in step S2a and the wavelength selected in step S2b (step S2c). Note that step S1 and steps S2a to S2c may be executed in any order, or may be executed simultaneously.

[0070] The background chromatogram acquired in step S2c is equivalent to the background chromatogram acquired in step S2 in the first embodiment. Thereafter, steps S3 to S13 similar to those in the first embodiment are executed using the two-dimensional sample chromatogram acquired in step S1 and the two-dimensional background chromatogram acquired in step S2c.

[0071] (4) Effects In this embodiment, the sample chromatogram acquired by the sample chromatogram acquisition unit 1 is a two-dimensional chromatogram showing the relationship between retention time and detection intensity. On the other hand, the background chromatogram acquired by the background chromatogram acquisition unit 2 is a three-dimensional chromatogram showing the relationship between retention time, detection intensity, and detection wavelength. The wavelengths in the three-dimensional background chromatogram are selected by the wavelength selection unit 8.

[0072] A two-dimensional selected background chromatogram corresponding to the wavelength selected by the wavelength selection unit 8 from the three-dimensional background chromatogram is acquired by the background chromatogram acquisition unit 2. The baselines of the two-dimensional sample chromatogram acquired by the sample chromatogram acquisition unit 1 and the selected background chromatogram are aligned by the alignment processing unit 3. In this way, the sample chromatogram and the background chromatogram are aligned.

[0073] According to this waveform processing, even in the waveform processing device 10 in which a three-dimensional background chromatogram is acquired, a two-dimensional sample chromatogram that contains almost no peaks or baseline fluctuations that are not attributable to the sample can be generated.

[0074] (5) Variations In this embodiment, a three-dimensional background chromatogram is generated using a detector 280 including a PDA, but the embodiment is not limited to this. A three-dimensional background chromatogram may be generated using a detector that does not include a PDA (e.g., detector 250) by sweeping the wavelength of the detection light. In this case, similar to the first embodiment, the analysis device 200 does not include a switching unit 270 and a detector 280.

[0075] [3] Third embodiment (1) Configuration of the analytical device Regarding the chromatogram waveform processing device and chromatogram waveform processing method according to the third embodiment, differences from the waveform processing device 10 according to the first embodiment will be described. FIG. 20 is a diagram showing an example of an analysis device 200 according to the third embodiment of the present invention. As shown in FIG. 20, the mass analysis device 200 includes a detector 280 instead of the detector 250. The configuration of the detector 280 is shown in FIG.

[0076] 20, when a sample chromatogram and a background chromatogram are both generated, the mobile phase is introduced to detector 280. Therefore, the generated sample chromatogram and background chromatogram are both three-dimensional chromatograms that show the relationship between the retention time and detection intensity of each component and the detection wavelength of detector 280.

[0077] Fig. 21 is a diagram showing an example of a sample chromatogram and a background chromatogram. In the upper part of Fig. 20, a two-dimensional sample chromatogram obtained by selecting an arbitrary wavelength from the three-dimensional sample chromatogram is shown by a dotted line. In addition, in the upper part of Fig. 20, a two-dimensional background chromatogram obtained by selecting the same wavelength from the three-dimensional background chromatogram is shown by a dotted line. In the lower part of Fig. 20, an enlarged view of the sample chromatogram and the background chromatogram in the upper part is shown.

[0078] (2) Waveform processing device Fig. 22 is a diagram showing a configuration of a waveform processing device 10. As shown in Fig. 22, in the waveform processing device 10 according to this embodiment, the alignment processing unit 3 further includes a wavelength alignment unit 3e. The operations of the subtraction processing unit 4, the replacement unit 5, the identification unit 6 and the presentation unit 7 are similar to those in the first embodiment.

[0079] The sample chromatogram acquisition unit 1 acquires a three-dimensional sample chromatogram from the analysis device 200. The background chromatogram acquisition unit 2 acquires a three-dimensional background chromatogram from the analysis device 200.

[0080] Here, the pseudo peaks of the sample chromatogram and the background chromatogram at the same wavelength are not necessarily aligned. The same is true for the baseline fluctuation. Therefore, the wavelength alignment unit 3e aligns the sample chromatogram and the background chromatogram in the wavelength direction so that the pseudo peaks or the baseline fluctuations are aligned.

[0081] The wavelength alignment unit 3e may automatically perform the alignment in the wavelength direction based on the correlation of the pseudo peak or baseline fluctuation between the sample chromatogram and the background chromatogram in a predetermined wavelength range. Alternatively, the wavelength alignment unit 3e may perform the alignment in the wavelength direction in response to an instruction from a user. In this case, the user can operate the operation unit 150 to specify the wavelength correspondence relationship between the sample chromatogram and the background chromatogram.

[0082] By performing the alignment in the wavelength direction, the sample chromatogram, each wavelength, and the corresponding wavelength of the background chromatogram are identified. The distance cost calculation unit 3a, the time alignment unit 3b, the search unit 3c, and the intensity alignment unit 3d perform the same operations as those in the first embodiment for each wavelength component of the sample chromatogram and the corresponding wavelength component of the background chromatogram.

[0083] In this embodiment, the sample chromatogram and the background chromatogram are aligned in the wavelength direction, but the embodiment is not limited to this. If the pseudo peaks and baseline fluctuations are consistent between the sample chromatogram and the background chromatogram at the same wavelength, the alignment in the wavelength direction does not need to be performed. In this case, the alignment processing unit 3 does not need to include the wavelength alignment unit 3e.

[0084] (3) Waveform processing Fig. 23 is a flowchart showing waveform processing by the waveform processing device 10 of Fig. 22. In the waveform processing of Fig. 23, step S1a is executed instead of step S1 in the waveform processing of Fig. 14. Also, step S2a is executed sequentially instead of step S2. Furthermore, step S3a is executed before step S3.

[0085] Specifically, the sample chromatogram acquisition unit 1 acquires a three-dimensional sample chromatogram from the analysis device 200 (step S1a). The background chromatogram acquisition unit 2 acquires a three-dimensional background chromatogram from the analysis device 200 (step S2a). Note that either step S1a or step S2a may be executed first, or they may be executed simultaneously.

[0086] Next, the wavelength alignment unit 3e performs wavelength alignment between the three-dimensional sample chromatogram acquired in step S1a and the three-dimensional sample chromatogram acquired in step S2a (step S3a), thereby identifying the sample chromatogram, each wavelength, and the corresponding wavelength of the background chromatogram.

[0087] Each wavelength component of the sample chromatogram is equivalent to the sample chromatogram acquired in step S1 of the first embodiment. Each wavelength component of the background chromatogram is equivalent to the background chromatogram acquired in step S2 of the first embodiment. Thereafter, steps S3 to S13 similar to those of the first embodiment are performed using each wavelength component of the sample chromatogram after wavelength alignment in step S3a and the corresponding wavelength component of the background chromatogram.

[0088] (4) Effects In this embodiment, the sample chromatogram acquired by the sample chromatogram acquisition unit 1 is a three-dimensional chromatogram showing the relationship between retention time, detection intensity, and detection wavelength. Similarly, each of the background chromatograms acquired by the background chromatogram acquisition unit 2 is a three-dimensional chromatogram showing the relationship between retention time, detection intensity, and detection wavelength.

[0089] The baselines of the wavelength components of the three-dimensional sample chromatogram acquired by the sample chromatogram acquisition unit 1 and the wavelength components of the three-dimensional background chromatogram acquired by the background chromatogram acquisition unit 2 and corresponding to the wavelengths of the three-dimensional sample chromatogram are aligned by the alignment processing unit 3. In this way, the sample chromatogram and the background chromatogram are aligned.

[0090] According to this waveform processing, in the waveform processing device 10 where a three-dimensional chromatogram is acquired, a three-dimensional sample chromatogram that contains almost no peaks or baseline fluctuations that are not attributable to the sample can be generated.

[0091] (5) Variations In this embodiment, the waveform processing device 10 does not include a wavelength selection unit 8, but the embodiment is not limited to this. The waveform processing device 10 may include the wavelength selection unit 8 of FIG. 18, similar to the second embodiment. In this case, by selecting an arbitrary wavelength, it is possible to obtain a two-dimensional selected sample chromatogram from a three-dimensional sample chromatogram, and obtain a two-dimensional selected background chromatogram from a three-dimensional background chromatogram. Therefore, the same waveform processing as in the first embodiment may be performed using the sample chromatogram selected as described above and the selected background chromatogram.

[0092] In this case, a two-dimensional selected sample chromatogram corresponding to the wavelength selected by the wavelength selection unit 8 from the three-dimensional sample chromatogram is acquired by the sample chromatogram acquisition unit 1. A two-dimensional selected background chromatogram corresponding to the wavelength selected by the wavelength selection unit 8 from the three-dimensional background chromatogram is acquired by the background chromatogram acquisition unit 2. The baselines of the selected sample chromatogram and the selected two-dimensional background chromatogram are aligned by the alignment processing unit 3. This allows alignment between the selected sample chromatogram and the selected background chromatogram.

[0093] According to this waveform processing, in the waveform processing device 10 where the three-dimensional chromatogram is acquired, a two-dimensional sample chromatogram that contains almost no peaks and baseline fluctuations that are not caused by the sample can be generated. In this case, the same wavelength may be selected for the three-dimensional sample chromatogram and the three-dimensional background chromatogram. On the other hand, when the pseudo peaks or baseline fluctuations are not uniform at the same wavelength, different wavelengths may be selected for the three-dimensional sample chromatogram and the three-dimensional background chromatogram so that the pseudo peaks or baseline fluctuations are uniform.

[0094] In addition, in this embodiment, a three-dimensional sample chromatogram and a three-dimensional background chromatogram are generated using a detector 280 including a PDA, but the embodiment is not limited to this. A three-dimensional sample chromatogram and a three-dimensional background chromatogram may be generated using a detector (e.g., detector 250) that does not include a PDA by sweeping the wavelength of the detection light. In this case, similar to the first embodiment, the analysis device 200 includes a detector 250 instead of the detector 280.

[0095] [4] Other embodiments (1) In the above embodiment, the analysis device 200 generates a background chromatogram by measuring a mobile phase into which no sample is injected, but the embodiment is not limited to this. The analysis device 200 may generate a background chromatogram by measuring a mobile phase into which a control sample is injected. The control sample is a known sample used to confirm the quantitativeness or reproducibility of the measurement.

[0096] When the mobile phase contains a control sample, a known peak due to the control sample also appears in the background chromatogram. The alignment processor 3 aligns the sample chromatogram with the background chromatogram while excluding the peak due to the control sample from the background chromatogram. With this configuration, alignment can be easily performed even when the background chromatogram is generated using the control sample.

[0097] (2) In the above embodiment, the background chromatogram acquiring unit 2 may acquire a plurality of background chromatograms. Also, the background chromatogram acquiring unit 2 may calculate statistics of the plurality of background chromatograms to acquire a representative background chromatogram that represents the plurality of background chromatograms.

[0098] In this case, the alignment processor 3 aligns the sample chromatogram with the representative background chromatogram. The representative background chromatogram contains almost no peaks that occur accidentally. This makes it possible to generate a chromatogram that enables more accurate analysis. The statistic may be an average value or another statistic such as a weighted average value.

[0099] (3) In the above embodiment, the modification function g(t) is applied to the background chromatogram, but the embodiment is not limited to this. If the baseline shift between the sample chromatogram and the background chromatogram in the intensity direction is small, the modification function g(t) does not need to be applied to the background chromatogram. In this case, the alignment processing unit 3 does not include the search unit 3c and the intensity alignment unit 3d.

[0100] (4) In the above embodiment, the process of replacing the distance cost with infinity or the process of adding the cost C to the distance cost is performed, but the embodiment is not limited to this. If the number of searches for the tentative corresponding point is sufficiently large, the process of replacing the distance cost with infinity and the process of adding the cost C to the distance cost may not be performed.

[0101] (5) In the above embodiment, the waveform processing device 10 includes the replacing unit 5, the identifying unit 6, and the presenting unit 7, but the embodiment is not limited to this. In the case where the portion of the sample chromatogram after the subtraction process that is equal to or less than a predetermined intensity does not need to be able to be replaced with 0, the waveform processing device 10 does not need to include the replacing unit 5. In addition, in the case where the peak derived from the sample does not need to be presented visibly in the original sample chromatogram, the waveform processing device 10 does not need to include the identifying unit 6 and the presenting unit 7.

[0102] [5] Aspects It will be appreciated by those skilled in the art that the exemplary embodiments described above are examples of the following aspects.

[0103] (Item 1) A chromatogram waveform processing device according to one embodiment comprises: a sample chromatogram acquisition unit that acquires a sample chromatogram generated by measuring a mobile phase into which a sample has been injected; a background chromatogram acquisition unit for acquiring a background chromatogram generated by measuring a mobile phase into which no sample is injected or a mobile phase into which a control sample is injected; an alignment processing unit that aligns the sample chromatogram acquired by the sample chromatogram acquisition unit with the background chromatogram acquired by the background chromatogram acquisition unit by aligning their baselines; The system may further include a subtraction processing unit that subtracts a background chromatogram from the sample chromatogram after alignment by the alignment processing unit.

[0104] In this chromatogram waveform processing device, the sample chromatogram and the background chromatogram are aligned so that the baselines are aligned. In this state, the background chromatogram is subtracted from the sample chromatogram, so that the sample chromatogram contains almost no peaks or baseline fluctuations that are not caused by the sample. This makes it possible to generate a chromatogram that enables accurate analysis.

[0105] (2) In the chromatogram waveform processing device according to (1), The alignment processing unit may align the baselines by matching the shapes of peaks or drifts of the sample chromatogram and the background chromatogram.

[0106] In this case, the baselines of the sample chromatogram and the background chromatogram can be aligned easily and accurately.

[0107] (Item 3) In the chromatogram waveform processing device according to item 1 or 2, the background chromatogram acquisition unit calculates statistics of a plurality of background chromatograms to acquire a representative background chromatogram that represents the plurality of background chromatograms; The alignment processing unit may align the sample chromatogram with the representative background chromatogram.

[0108] In this case, the representative background chromatogram contains few incidental peaks, which allows for a more accurate analysis.

[0109] (Item 4) In the chromatogram waveform processing device according to any one of items 1 to 3, When a known peak derived from a control sample is included in the background chromatogram, the alignment processing unit may perform alignment by excluding the peak.

[0110] According to this configuration, even if the background chromatogram is generated using a control sample, alignment of the sample chromatogram with the background chromatogram can be easily performed.

[0111] (Item 5) In the chromatogram waveform processing device according to any one of items 1 to 4, The alignment processing unit includes: a distance cost calculation unit that determines one or more points in the background chromatogram that provisionally correspond to each of a plurality of points in the sample chromatogram as provisional corresponding points, calculates a distance between each point in the sample chromatogram and the provisional corresponding point in the background chromatogram, and calculates a sum of the distances calculated for the plurality of points in the sample chromatogram as a distance cost; The system may also include a time alignment unit that updates tentative corresponding points in the background chromatogram for each point in the sample chromatogram, determines the tentative corresponding point that has the smallest distance cost as the confirmed corresponding point, and performs alignment in the time direction based on each point in the sample chromatogram and the confirmed corresponding point in the background chromatogram.

[0112] In this case, the sample chromatogram and the background chromatogram can be more accurately associated, thereby generating a chromatogram that allows for more accurate analysis.

[0113] (Item 6) In the chromatogram waveform processing device according to item 5, The alignment processing unit includes: a search unit that searches for a modification function that modifies the background chromatogram so as to reduce a baseline variation of the background chromatogram relative to a baseline of the sample chromatogram; The system may further include an intensity alignment unit that performs intensity direction alignment between the sample chromatogram and the background chromatogram to which the transformation function searched for by the search unit has been applied.

[0114] According to this configuration, even if there is a large deviation in the baseline between the sample chromatogram and the background chromatogram in the intensity direction, the sample chromatogram and the background chromatogram can be accurately aligned.

[0115] (Item 7) In the chromatogram waveform processing device according to item 5 or 6, When a distance included in the calculated distance cost exceeds a predetermined upper limit, the distance cost calculation unit may calculate the distance cost by setting the distance to a constant value.

[0116] In this case, the distance cost can be calculated while excluding peaks due to the sample, which allows accurate alignment of the sample chromatogram with the background chromatogram.

[0117] (Item 8) In the chromatogram waveform processing device according to item 7, The upper limit may be a constant multiple of the amount of noise in the chromatograph generating the sample chromatogram and the background chromatogram.

[0118] In this case, an appropriate upper limit for the distance can be easily determined based on the amount of noise in the chromatograph.

[0119] (Item 9) In the chromatogram waveform processing device according to item 8, The distance cost calculation unit may estimate the amount of noise from a background chromatogram.

[0120] In this case, an appropriate upper limit of the distance can be easily determined based on the amount of noise estimated from the background chromatogram.

[0121] (Item 10) In the chromatogram waveform processing device according to any one of items 5 to 9, The distance cost calculation unit may, when a point in a sample chromatogram and a tentative corresponding point for the point in a background chromatogram are shifted by a predetermined time or more, replace a distance cost including a distance between the two points with infinity.

[0122] In this case, alignment is prevented in which the position of a peak in the background chromatogram is aligned with the position of a non-corresponding peak in the sample chromatogram.

[0123] (Item 11) In the chromatogram waveform processing device according to any one of items 5 to 9, The distance cost calculation unit may increase the distance cost according to the magnitude of a time shift between a given point in a sample chromatogram and a tentative corresponding point for the given point in a background chromatogram.

[0124] In this case, alignment is prevented in which the position of a peak in the background chromatogram is aligned with the position of a non-corresponding peak in the sample chromatogram.

[0125] (Item 12) The chromatogram waveform processing device according to any one of items 1 to 11, The apparatus may further include a replacing unit that replaces portions of the sample chromatogram that have been subjected to the subtraction process by the subtraction processing unit that have an intensity equal to or lower than a predetermined intensity with zero.

[0126] In this case, the user can observe a sample chromatogram from which noise has been removed.

[0127] (Item 13) The chromatogram waveform processing device according to any one of items 1 to 12, an identifying unit that identifies a peak derived from a sample based on the sample chromatogram that has been subjected to the subtraction processing by the subtraction processing unit; The system may further comprise a presentation unit that visually presents peaks derived from the sample based on the identification result by the identification unit in the sample chromatogram before the subtraction process is performed.

[0128] In this case, the user can easily recognize peaks originating from the sample in the original sample chromatogram.

[0129] (Item 14) In the chromatogram waveform processing device according to any one of items 1 to 13, the sample chromatogram acquired by the sample chromatogram acquisition unit is a two-dimensional chromatogram showing the relationship between retention time and detection intensity; the background chromatogram acquired by the background chromatogram acquisition unit is a three-dimensional chromatogram showing the relationship between retention time, detection intensity, and detection wavelength; The chromatogram waveform processing device further includes a wavelength selection unit that selects a wavelength in a three-dimensional background chromatogram, the background chromatogram acquisition unit acquires a two-dimensional selected background chromatogram corresponding to the wavelength selected by the wavelength selection unit from the three-dimensional background chromatogram; The alignment processing unit may align the sample chromatogram and the background chromatogram by aligning the baselines of the two-dimensional sample chromatogram acquired by the sample chromatogram acquisition unit and the selected background chromatogram.

[0130] In this case, even in a chromatogram waveform processing device that acquires a three-dimensional background chromatogram, a two-dimensional sample chromatogram that contains almost no peaks or baseline fluctuations that are not attributable to the sample can be generated.

[0131] (Item 15) In the chromatogram waveform processing device according to any one of items 1 to 13, each of the sample chromatogram acquired by the sample chromatogram acquisition unit and the background chromatogram acquired by the background chromatogram acquisition unit is a three-dimensional chromatogram showing a relationship between retention time, detection intensity, and detection wavelength; The alignment processing unit may align the sample chromatogram with the background chromatogram by aligning the baselines of each wavelength component of the three-dimensional sample chromatogram acquired by the sample chromatogram acquisition unit and each wavelength component of the three-dimensional background chromatogram acquired by the background chromatogram acquisition unit and corresponding to each wavelength of the three-dimensional sample chromatogram.

[0132] In this case, in the chromatogram waveform processing device that acquires the three-dimensional chromatogram, it is possible to generate a three-dimensional sample chromatogram that contains almost no peaks or baseline fluctuations that are not attributable to the sample.

[0133] (Item 16) In the chromatogram waveform processing device according to any one of items 1 to 13, each of the sample chromatogram acquired by the sample chromatogram acquisition unit and the background chromatogram acquired by the background chromatogram acquisition unit is a three-dimensional chromatogram showing a relationship between retention time, detection intensity, and detection wavelength; The chromatogram waveform processing device further includes a wavelength selection unit that selects a wavelength in a three-dimensional sample chromatogram and a wavelength in a three-dimensional background chromatogram, the sample chromatogram acquisition unit acquires a two-dimensional selected sample chromatogram corresponding to the wavelength selected by the wavelength selection unit from the three-dimensional sample chromatogram; the background chromatogram acquisition unit acquires a two-dimensional background chromatogram corresponding to the wavelength selected by the wavelength selection unit from the three-dimensional background chromatogram; The alignment processing unit may align the selected sample chromatogram with the selected background chromatogram by aligning baselines of the selected sample chromatogram with those of the selected background chromatogram.

[0134] In this case, in the chromatogram waveform processing device that acquires a three-dimensional chromatogram, a two-dimensional sample chromatogram that contains almost no peaks or baseline fluctuations that are not attributable to the sample can be generated.

[0135] (Item 17) In the chromatogram waveform processing device according to any one of items 14 to 16, The three-dimensional chromatogram may be generated using a detector that includes a photodiode array.

[0136] In this case, a three-dimensional chromatogram can be easily obtained.

[0137] (Item 18) A chromatogram waveform processing method according to another aspect includes the steps of: obtaining a sample chromatogram generated by measuring a mobile phase into which the sample is injected; obtaining a background chromatogram generated by measuring a mobile phase in which no sample is injected or a mobile phase in which a control sample is injected; aligning the sample chromatogram with the background chromatogram by aligning the baselines of the acquired sample chromatogram with the acquired background chromatogram; and subtracting the background chromatogram from the aligned sample chromatogram.

[0138] According to this chromatogram waveform processing method, the sample chromatogram after subtraction contains almost no peaks and baseline fluctuations that are not caused by the sample, thereby generating a chromatogram that enables accurate analysis. [Explanation of symbols]

[0139] 1...sample chromatogram acquisition unit, 2...background chromatogram acquisition unit, 3...alignment processing unit, 3a...distance cost calculation unit, 3b...time alignment unit, 3c...search unit, 3d...intensity alignment unit, 3e...wavelength alignment unit, 4...subtraction processing unit, 5...substitution unit, 6...identification unit, 7...presentation unit, 8...wavelength selection unit, 10...waveform processing unit, 100...control unit, 110...CPU, 120...RAM, 130...ROM, 140...storage unit, 150...operation unit, 160...display unit, 170...input / output I / F, 180...bus, 200...analysis device, 300...analysis system, p1, p2, P1, P2...pseudo peak, Q, Q1 to Q16...peak

Claims

1. a sample chromatogram acquisition unit that acquires a sample chromatogram generated by measuring a mobile phase into which a sample has been injected; a background chromatogram acquisition unit for acquiring a background chromatogram generated by measuring a mobile phase into which no sample is injected or a mobile phase into which a control sample is injected; an alignment processing unit that aligns the sample chromatogram acquired by the sample chromatogram acquisition unit with the background chromatogram acquired by the background chromatogram acquisition unit by aligning their baselines; a subtraction processing unit that subtracts a background chromatogram from the sample chromatogram after alignment by the alignment processing unit.

2. 2. The chromatogram waveform processing device according to claim 1, wherein said alignment processing section aligns baselines by matching peak or drift shapes of a sample chromatogram and a background chromatogram.

3. the background chromatogram acquisition unit calculates statistics of a plurality of background chromatograms to acquire a representative background chromatogram that represents the plurality of background chromatograms; 3. The chromatogram waveform processing device according to claim 1, wherein said alignment processing section aligns a sample chromatogram with a representative background chromatogram.

4. 4. The chromatogram waveform processing device according to claim 1, wherein, when a known peak derived from a control sample is included in a background chromatogram, the alignment processing unit performs alignment by excluding the peak.

5. The alignment processing unit includes: a distance cost calculation unit that determines one or more points in the background chromatogram that provisionally correspond to each of a plurality of points in the sample chromatogram as provisional corresponding points, calculates a distance between each point in the sample chromatogram and the provisional corresponding point in the background chromatogram, and calculates a sum of the distances calculated for the plurality of points in the sample chromatogram as a distance cost; 5. The chromatogram waveform processing device according to claim 1, further comprising: a time alignment unit that updates a tentative corresponding point in the background chromatogram for each point in the sample chromatogram, determines the tentative corresponding point when the distance cost is minimum as a definite corresponding point, and performs alignment in the time direction based on each point in the sample chromatogram and the definite corresponding point in the background chromatogram.

6. The alignment processing unit includes: a search unit that searches for a modification function that modifies the background chromatogram so as to reduce a baseline variation of the background chromatogram relative to a baseline of the sample chromatogram; 6. The chromatogram waveform processing device according to claim 5, further comprising an intensity alignment section for performing intensity direction alignment between the sample chromatogram and the background chromatogram to which the transformation function searched for by said search section has been applied.

7. 7. The chromatogram waveform processing device according to claim 5, wherein, when a distance included in the calculated distance cost exceeds a predetermined upper limit, the distance cost calculation section calculates the distance cost by setting the distance to a constant value.

8. 8. The chromatogram waveform processing device according to claim 7, wherein the upper limit is a constant multiple of the amount of noise in a chromatograph that generates the sample chromatogram and the background chromatogram.

9. The chromatogram waveform processing device according to claim 8 , wherein the distance cost calculation section estimates the amount of noise from a background chromatogram.

10. 10. The chromatogram waveform processing device according to claim 5, wherein, when a point on a sample chromatogram and a tentative corresponding point for the point on a background chromatogram are shifted by a predetermined time or more, the distance cost calculation unit replaces a distance cost including a distance between the two points with infinity.

11. 10. The chromatogram waveform processing device according to claim 5, wherein the distance cost calculation unit increases the distance cost according to the magnitude of a time shift between an arbitrary point in a sample chromatogram and a tentative corresponding point for the arbitrary point in a background chromatogram.

12. The chromatogram waveform processing device according to claim 1 , further comprising a replacement unit that replaces portions of the sample chromatogram that have been subjected to the subtraction process by the subtraction processing unit that have an intensity equal to or lower than a predetermined intensity with zero.

13. an identifying unit that identifies a peak derived from a sample based on the sample chromatogram that has been subjected to the subtraction processing by the subtraction processing unit; The chromatogram waveform processing device according to any one of claims 1 to 12, further comprising a presentation unit that visually presents peaks derived from the sample based on the identification result by the identification unit in the sample chromatogram before the subtraction process is performed.

14. the sample chromatogram acquired by the sample chromatogram acquisition unit is a two-dimensional chromatogram showing the relationship between retention time and detection intensity; the background chromatogram acquired by the background chromatogram acquisition unit is a three-dimensional chromatogram showing the relationship between retention time, detection intensity, and detection wavelength; The chromatogram waveform processing device further includes a wavelength selection unit that selects a wavelength in a three-dimensional background chromatogram, the background chromatogram acquisition unit acquires a two-dimensional selected background chromatogram corresponding to the wavelength selected by the wavelength selection unit from the three-dimensional background chromatogram; The chromatogram waveform processing device according to any one of claims 1 to 13, wherein the alignment processing unit aligns the sample chromatogram and the background chromatogram by aligning the baselines of the two-dimensional sample chromatogram acquired by the sample chromatogram acquisition unit and the selected background chromatogram.

15. each of the sample chromatogram acquired by the sample chromatogram acquisition unit and the background chromatogram acquired by the background chromatogram acquisition unit is a three-dimensional chromatogram showing a relationship between retention time, detection intensity, and detection wavelength; The chromatogram waveform processing device according to any one of claims 1 to 13, wherein the alignment processing unit aligns the sample chromatogram and the background chromatogram by aligning baselines between each wavelength component of the three-dimensional sample chromatogram acquired by the sample chromatogram acquisition unit and each wavelength component of the three-dimensional background chromatogram acquired by the background chromatogram acquisition unit and corresponding to each wavelength of the three-dimensional sample chromatogram.

16. each of the sample chromatogram acquired by the sample chromatogram acquisition unit and the background chromatogram acquired by the background chromatogram acquisition unit is a three-dimensional chromatogram showing a relationship between retention time, detection intensity, and detection wavelength; The chromatogram waveform processing device further includes a wavelength selection unit that selects a wavelength in a three-dimensional sample chromatogram and a wavelength in a three-dimensional background chromatogram, the sample chromatogram acquisition unit acquires a two-dimensional selected sample chromatogram corresponding to the wavelength selected by the wavelength selection unit from the three-dimensional sample chromatogram; the background chromatogram acquisition unit acquires a two-dimensional selected background chromatogram corresponding to the wavelength selected by the wavelength selection unit from the three-dimensional background chromatogram; The chromatogram waveform processing device according to any one of claims 1 to 13, wherein the alignment processing unit aligns the selected sample chromatogram with the selected background chromatogram by aligning baselines of the selected sample chromatogram with the selected background chromatogram.

17. The chromatogram waveform processing device according to any one of claims 14 to 16, wherein the three-dimensional chromatogram is generated using a detector including a photodiode array.

18. obtaining a sample chromatogram generated by measuring a mobile phase into which the sample is injected; obtaining a background chromatogram generated by measuring a mobile phase in which no sample is injected or a mobile phase in which a control sample is injected; aligning the sample chromatogram with the background chromatogram by aligning the baselines of the acquired sample chromatogram with the acquired background chromatogram; and a step of subtracting a background chromatogram from the aligned sample chromatogram.

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