Detection device, detection method, detection program, and detection system

Abstract

To appropriately identify the peak of a chromatogram as the peak of a target component.SOLUTION: A detection device (100) comprises an acquisition unit (104) for acquiring a plurality of detection data corresponding to each of a plurality of samples (samples S1-S3), and a computation unit (101) for processing the plurality of detection data. The computation unit acquires an identification result indicating that the peak information of signal strength extracted from each of the plurality of detection data has been identified as the peak information of signal strength corresponding to a target component, and detects that, when peak information of an outlier exists in the plurality of pieces of peak information identified in each of the plurality of detection data, the identification result corresponding to the peak information of the outlier is abnormal.SELECTED DRAWING: Figure 5

Description

[Technical Field]

[0001] The present disclosure relates to a detection device, a detection method, a detection program, and a detection system. [Background technology]

[0002] As disclosed in Patent Document 1 (JP 2023-012485 A), a technique called chromatography is known that uses a chromatograph to separate components contained in a sample to be analyzed. Chromatography is applied to analysis in the field of metabolomics, which comprehensively analyzes specific molecules produced by cellular activity, and to pesticide residue analysis. The chromatograph in Patent Document 1 automatically identifies target components by using a peak detection algorithm to detect peaks in signal intensity in a chromatogram. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Japanese Patent Publication No. 2023-012485 Summary of the Invention [Problem to be solved by the invention]

[0004] Samples to be analyzed by chromatography may contain contaminants, and even samples obtained under the same conditions may have variations in the types and concentrations of components contained within the sample. The chromatograph described in Patent Document 1 does not take into consideration the effects of contaminants or component variations, and therefore may not properly identify the target component. For example, there is a risk of identifying the wrong peak as the peak of the target component, or identifying part of the peak shape as the wrong shape.

[0005] To determine whether the peak detection algorithm has properly identified the desired peak as a peak of the target component, a user must visually confirm the peak. In metabolomics analysis and pesticide residue analysis, the number of samples and the number of target components can reach several hundred. It is cumbersome for a user to visually confirm whether each of the hundreds of target components contained in several hundred samples has been properly identified.

[0006] The present disclosure has been made to solve the above-mentioned problems, and its purpose is to appropriately identify peaks in a chromatogram as peaks of a target component. [Means for solving the problem]

[0007] A detection device according to an aspect of the present disclosure includes an acquisition unit that acquires multiple pieces of detection data corresponding to each of multiple samples detected by a chromatograph, and a calculation unit that processes the multiple pieces of detection data acquired by the acquisition unit. The calculation unit acquires an identification result indicating that signal intensity peak information extracted from each of the multiple pieces of detection data has been identified as signal intensity peak information corresponding to a target component, and if outlier peak information is present among the multiple peak information identified in each of the multiple pieces of detection data, detects that the identification result corresponding to the outlier peak information is abnormal.

[0008] A detection method according to another aspect of the present disclosure is a detection method in which a computer detects an abnormality in an identification result of a target component, the detection method including the steps of acquiring a plurality of detection data corresponding to each of a plurality of samples detected by a chromatograph and processing the plurality of detection data acquired by the acquiring step, The processing step includes the steps of acquiring an identification result indicating that signal intensity peak information extracted from each of the plurality of detection data has been identified as signal intensity peak information corresponding to the target component, and, if outlier peak information is present among the plurality of peak information identified in each of the plurality of detection data, detecting that the identification result corresponding to the outlier peak information is abnormal.

[0009] A detection program according to another aspect of the present disclosure is a detection program for detecting an abnormality in an identification result of a target component, the detection program causing a computer to execute the steps of acquiring a plurality of detection data corresponding to each of a plurality of samples detected by a chromatograph and processing the plurality of detection data acquired by the acquiring step. The processing step includes the steps of acquiring an identification result indicating that signal intensity peak information extracted from each of the plurality of detection data has been identified as signal intensity peak information corresponding to the target component, and, if outlier peak information is present among the plurality of peak information identified in each of the plurality of detection data, detecting that the identification result corresponding to the outlier peak information is abnormal.

[0010] According to another aspect of the present disclosure, a detection system includes a chromatograph and a detection device that detects an abnormality in an identification result of a target component. The detection device includes an acquisition unit that acquires multiple pieces of detection data corresponding to multiple samples detected by the chromatograph, and a calculation unit that processes the multiple pieces of detection data acquired by the acquisition unit. The calculation unit acquires an identification result indicating that signal intensity peak information extracted from each of the multiple pieces of detection data has been identified as signal intensity peak information corresponding to the target component, and if outlier peak information is present among the multiple peak information identified in each of the multiple pieces of detection data, detects that the identification result corresponding to the outlier peak information is abnormal. [Effects of the Invention]

[0011] According to the present disclosure, peaks in a chromatogram can be appropriately identified as peaks of a target component. [Brief explanation of the drawings]

[0012] [Figure 1] 1 is a diagram showing the configuration of a detection system and a detection device according to a first embodiment. [Figure 2] 10 is a flowchart showing a process for acquiring an identification result. [Figure 3] FIG. 3 is a diagram showing a display example of a chromatogram generated by the detection device in the first embodiment. [Figure 4] FIG. 3 is a diagram showing an example of a table of peak information according to the first embodiment. [Figure 5] 10 is a flowchart showing an abnormality detection process for an identification result. [Figure 6] FIG. 6 is a diagram showing an example of a chromatogram displayed after the flowchart of FIG. 5 is executed. [Figure 7] FIG. 6 is a diagram showing an example of a table of peak information displayed after the flowchart of FIG. 5 is executed. [Figure 8] FIG. 10 is a diagram showing a display example of a chromatogram generated by the detection device in the second embodiment. [Figure 9]FIG. 11 is a diagram showing an example of a table of peak information in the second embodiment. [Figure 10] FIG. 6 is a diagram showing an example of a chromatogram displayed after the flowchart of FIG. 5 is executed in the second embodiment. [Figure 11] FIG. 6 is a diagram showing an example of a table of peak information displayed after the flowchart of FIG. 5 is executed in the second embodiment. DETAILED DESCRIPTION OF THE INVENTION

[0013] [Embodiment 1] The present embodiment will be described in detail with reference to the drawings. In the drawings, the same or corresponding parts are designated by the same reference numerals, and their description will not be repeated in principle.

[0014] <Overall configuration of the detection system and detection device> The configurations of a detection system 1 and a detection device 100 according to embodiment 1 will be described with reference to Fig. 1. Fig. 1 is a diagram showing the configurations of a detection system 1 and a detection device 100 according to embodiment 1. As shown in Fig. 1, the detection system 1 includes a chromatograph 10 and a detection device 100.

[0015] The chromatograph 10 includes a container 11, a liquid delivery pump 12, an injector 13, a column 14, and a detector 15. The container 11 contains a mobile phase. The liquid delivery pump 12 draws the mobile phase from the container 11 and delivers it at a constant flow rate. The injector 13 injects a sample to be analyzed into the mobile phase delivered by the liquid delivery pump 12.

[0016] The column 14 contains a stationary phase and separates various components contained in the sample injected by the injector 13. The detector 15 detects the components eluted from the column 14. As the detector 15, for example, an absorptiometry detector (a PDA (Photo Diode Array) detector), a fluorescence detector, a differential refractive index detector, a conductivity detector, or a mass spectrometer may be used. Detection data indicating the signal intensity corresponding to the components in the sample detected by the detector 15 is output to the detection device 100.

[0017] Although the chromatograph 10 according to the first embodiment is a liquid chromatograph (LC) that uses a liquid as the mobile phase, the chromatograph 10 may be another chromatograph such as a gas chromatograph that uses a gas as the mobile phase.

[0018] In the chromatograph 10, an injector 13 injects a sample to be analyzed into a mobile phase. The injected sample travels with the flow of mobile phase delivered by the liquid delivery pump 12 to a column 14, where it passes through the column 14. The various components contained in the sample take different amounts of time to pass through the column 14 depending on their affinity with the stationary phase or the mobile phase. For example, among the components contained in the sample, components that are easily adsorbed to the stationary phase take longer to pass through the column 14 (also referred to as "retention time") than components that are less easily adsorbed to the stationary phase. This allows the various components contained in the sample to be separated in the time direction by the column 14.

[0019] The eluate containing the components separated in the column 14 is introduced from the column 14 into the detector 15. The detector 15 outputs detection data indicating signal intensity corresponding to the concentration (amount) of the components introduced by the column 14. The detection data is processed by the detection device 100 to generate a chromatogram. The solution that has passed through the detector 15 is discharged as waste liquid.

[0020] The detection device 100 may be a general-purpose computer or a computer dedicated to the detection system 1 for processing detection data from the chromatograph 10. The detection device 100 includes a calculation device 101, a memory 102, a storage device 103, an interface 104, a display device 110, and an input device 120.

[0021] The arithmetic device 101 is an example of a "arithmetic unit." The arithmetic device 101 is a computing entity (computer) that executes various processes by executing various programs. The arithmetic device 101 is configured with a processor such as a CPU (central processing unit) or an MPU (micro-processing unit). Note that a processor, which is an example of the arithmetic device 101, has the function of executing various processes by executing programs, but some or all of these functions may be implemented using dedicated hardware circuits such as an ASIC (application specific integrated circuit) or an FPGA (field-programmable gate array).

[0022] The term "processor" is not limited to a processor in the narrow sense that executes processing using a stored program, such as a CPU or MPU, but may also include hardwired circuits such as an ASIC or FPGA. Therefore, the term "processor," which is an example of the arithmetic device 101, can also be interpreted as processing circuitry whose processing is predefined by computer-readable code and / or hardwired circuits.

[0023] The computing device 101 may be configured as a single chip or multiple chips. Furthermore, the processor and related processing circuits may be configured as multiple computers interconnected by wire or wirelessly via a local area network or a wireless network. The processor and related processing circuits may be configured as a cloud computer that performs remote calculations based on input data and outputs the calculation results to another device in a remote location.

[0024] The memory 102 includes a volatile storage area (for example, a working area) that temporarily stores program code, work memory, etc. when the arithmetic device 101 executes various programs. Examples of the storage unit include volatile memories such as DRAM (dynamic random access memory) and SRAM (static random access memory), and non-volatile memories such as ROM (read only memory) and flash memory.

[0025] The storage device 103 stores various programs and various data executed by the arithmetic device 101. The storage device 103 may be one or more non-transitory computer readable media, or one or more computer readable storage media. Examples of the storage device 103 include a hard disk drive (HDD) and a solid state drive (SSD).

[0026] The memory device 103 according to the first embodiment stores a detection program 130 for executing a process for detecting abnormalities in the detection data acquired by the calculation device 101 from the chromatograph 10, and an acquisition program 135 for acquiring the identification results of the target component, which will be described later.

[0027] The interface 104 transmits and receives data to and from an external device or equipment via wired or wireless communication. For example, the interface 104 communicates with the chromatograph 10 to acquire detection data output from the chromatograph 10. The interface 104 may also be a communication device that communicates with a cloud server (not shown) to transmit detection data acquired from the chromatograph 10 to the cloud server, or transmits execution results of the arithmetic device 101's abnormal data detection process to the cloud server.

[0028] Furthermore, the interface 104 may transmit and receive data to and from the user interface, the display device 110 or the input device 120, via wired or wireless communication. The detection device 100 is not limited to having one interface 104, but may have multiple interfaces 104 depending on the number of communication targets.

[0029] The display device 110 is, for example, a display configured with a liquid crystal panel or the like, and displays the execution result of the abnormal data detection process performed by the detection device 100. The input device 120 is, for example, a pointing device such as a keyboard or a mouse, and receives commands from a user. When a touch panel is used as the user interface, the display device 110 and the input device 120 may be integrally formed. Note that the display device 110 and the input device 120 may be provided separately from the detection device 100.

[0030] <Obtaining identification results> In the detection system 1 configured as described above, the detection device 100 acquires, via the interface 104, detection data in time series that indicates signal intensities corresponding to components in a sample detected by the chromatograph 10. Based on the acquired detection data, the detection device 100 generates a chromatogram that indicates changes in signal intensity over time. The chromatogram includes waveforms of multiple peak shapes (also simply referred to as "peaks"). The multiple peaks included in the chromatogram correspond to multiple components in the sample, respectively.

[0031] The detection device 100 in the first embodiment uses a peak detection algorithm to automatically determine which of multiple peaks contained in a chromatogram corresponds to a target component. The target component is a component to be analyzed among multiple components contained in a sample, and is set in advance by the user of the detection system 1.

[0032] As described above, the components in the sample are separated by the column 14. Peaks in the chromatogram are formed at retention times specific to each component. The theoretical retention times (also referred to as "theoretical retention times") of the target components are input in advance by the user and stored in the storage device 103.

[0033] The detection device 100 automatically identifies, among the multiple peaks in a chromatogram, a peak that is formed at a retention time close to the theoretical retention time of the target component as the peak corresponding to the target component. Identifying one peak among the multiple peaks included in a chromatogram as the peak of the target component in this manner is called "identification."

[0034] The detection apparatus 100 acquires information (also referred to as "peak information") about peaks identified as peaks of the target component as identification results. The peak information includes, for example, the maximum value of the signal intensity, the retention time when the signal intensity is at its maximum value (also referred to as "peak retention time"), the retention time when the signal intensity starts to rise (referred to as "peak start retention time"), the retention time when the signal intensity finishes falling (referred to as "peak end retention time"), the area of ​​the peak shape (referred to as "peak area"), the position of the baseline (described later), and the intensity obtained by subtracting the intensity of the baseline from the maximum value of the signal intensity (also referred to as "peak height").

[0035] The detection device 100 calculates the concentration of the target component contained in the sample using the peak height, peak area, and a previously prepared calibration curve. In this way, the detection device 100 of the first embodiment obtains an identification result indicating that the signal intensity peak information extracted from the detection data has been identified as the signal intensity peak information corresponding to the target component.

[0036] 2 is a flowchart showing a process for acquiring an identification result. The processing steps shown in FIG. 2 are realized by the arithmetic device 101 executing the identification result acquisition program 135.

[0037] 2, the arithmetic device 101 acquires detection data indicating signal intensities corresponding to components in a sample detected by the chromatograph 10 (step S110). The arithmetic device 101 generates a chromatogram based on the detection data (step S120).

[0038] The arithmetic device 101 executes a correction process for the retention time (step S130). The retention time of the chromatogram may vary due to deterioration of the column 14, even when the same component passes through the column 14. The process of step S130 is a process for correcting the variation in retention time due to deterioration of the column 14, etc.

[0039] In the first embodiment, a standard substance (e.g., an alkane) is used to correct the variation in retention time. In the first embodiment, the standard substance is mixed into the sample to generate a chromatogram. The retention time of the standard substance when the column 14 is not degraded is input in advance to the detection device 100. The detection device 100 determines the degree of degradation of the column 14 using the retention time of the standard substance in the generated chromatogram and the retention time of the standard substance when the column 14 is not degraded, and corrects the retention time of the entire chromatogram.

[0040] In one aspect, the retention time may be corrected without using a standard substance, using the retention time of a given component when the column 14 is not deteriorated and the retention time when the given component is actually detected. In another aspect, the retention time may be corrected by correcting the flow rate of the mobile phase. In this way, the detection device 100 of the first embodiment performs a correction process on the retention time of the chromatogram in advance, taking into account fluctuations in retention time due to external factors such as deterioration of the column 14.

[0041] 2, the arithmetic device 101 obtains the identification result of the target component from among the multiple peaks included in the chromatogram whose retention times have been corrected in step S130 using a peak detection algorithm (step S140), and then ends the process. The processes of steps S110 to S140 shown in FIG. 2 are processes for obtaining the identification result of one target component for one sample.

[0042] <Identification results for multiple samples> FIG. 2 illustrates the process of obtaining the identification result of one target component in one sample. In the first embodiment, the identification results of the target components are obtained from multiple samples. That is, the detection device 100 of the first embodiment executes the flowchart shown in FIG. 2 as many times as the number of multiple samples prepared in advance. As described above, in analyses in the field of metabolomics and pesticide residue analysis, the number of samples can reach several hundred.

[0043] More specifically, in a pesticide residue analysis to determine whether agricultural products to be shipped contain pesticides, some of the products are randomly selected as samples. An example will be described below in which 100 products are selected as samples. In this case, the detection device 100 executes the flowchart of FIG. 2 for each of the 100 products. The 100 products are the same type of agricultural product. More specifically, if the products are bananas, the 100 products will not contain any agricultural products other than bananas, and all of the 100 products will be bananas. Therefore, the 100 samples will basically have common components.

[0044] In the first embodiment, a case will be described in which target component A, which is a pesticide, is set as the target component. The theoretical retention time of target component A is 7.14 minutes. In the first embodiment, the flowchart of FIG. 2 is executed for each of 100 shipped products to generate 100 chromatograms. The detection device 100 performs an identification process for each of the 100 chromatograms, automatically identifying peaks formed at retention times close to 7.14 minutes as peaks corresponding to target component A.

[0045] 3 is a diagram showing an example of a display of a chromatogram generated by the detection device 100 in the first embodiment. Chromatograms C1, C2, and C3 corresponding to three samples S1, S2, and S3 out of 100 samples are shown in FIG. 3. In each of the chromatograms C1, C2, and C3, the horizontal axis indicates retention time (minutes) and the vertical axis indicates signal intensity (absorbance). Chromatograms C1 to C3 shown in FIG. 3 are displayed to the user as image data by the display device 110.

[0046] As described above, the 100 samples are the same type of agricultural product. Therefore, most of the components contained in the 100 samples have common components. In the example of the first embodiment, an example is described in which most of the 100 samples contain target component A. However, as shown in FIG. 3, the peak shapes contained in each of the chromatograms C1 to C3 may differ due to the inclusion of impurity components in the samples or variations in the components.

[0047] In the example of FIG. 3, in chromatograms C1 and C2, a peak with a signal intensity exceeding 5000 is formed at a retention time of 7.14 minutes. On the other hand, in chromatogram C3, a peak with a signal intensity of approximately 2000, which is less than 5000, is formed at a retention time of 7.14 minutes. Also, in chromatogram C3, a peak with a signal intensity of approximately 3000 is formed at a retention time of 7.30 minutes. On the other hand, in chromatograms C1 and C2, no peak is formed at a retention time of 7.30 minutes.

[0048] Thus, even for the same type of samples S1, S2, and S3 collected under the same conditions, the peak shapes differ due to the presence of impurity components or variations in components. As described above, the detection device 100 of the first embodiment identifies the target component A for each of the chromatograms C1, C2, and C3 using a peak detection algorithm. In FIG. 3, white triangular images P1, P2, and P3 are displayed for the peaks of each of the chromatograms C1 to C3, respectively. Images P1, P2, and P3 indicate that the peaks indicated by images P1, P2, and P3 have been identified as the target component A.

[0049] That is, image P1 shows that the peak at retention time "7.14 minutes" in chromatogram C1 is the peak of target component A. Image P2 shows that the peak at retention time "7.14 minutes" in chromatogram C2 is the peak of target component A. On the other hand, image P3 shows that the peak at retention time "7.30 minutes" in chromatogram C3 is the peak of target component A.

[0050] As shown in Figure 3, in chromatogram C3, a false peak (a peak with a signal intensity of approximately "3000") has been identified as target component A. This is because the concentration of target component A contained in sample S3 is lower than that of the other samples, and because of component variation, an impurity component with a retention time of "7.30 minutes" has been mixed into sample S3.

[0051] As a result, the detection device 100 erroneously identifies the peak corresponding to the impurity component formed at retention time "7:30 minutes" as target component A. In this way, in the example shown in FIG. 3, the peak detection algorithm is used to automatically identify target component A, resulting in erroneous peak identification as target component A in some samples. Therefore, in the first embodiment, the following method is used to detect erroneous identification as an abnormality.

[0052] <Anomaly detection processing of identification results> The detection device 100 acquires peak information of the identified target component A in each of the chromatograms C1 to C3. FIG. 4 is a diagram showing an example of a peak information table in the first embodiment. The table shown in FIG. 4 is displayed to the user as image data by the display device 110, similar to FIG. 3. In the first embodiment, the peak information is peak retention time. The detection device 100 acquires peak retention times corresponding to the identified peaks and generates the table shown in FIG. 4. The table shown in FIG. 4 is stored in the storage device 103.

[0053] As shown in FIG. 4, the peak retention time of target component A in chromatogram C1 is 7.14 minutes. The peak retention time of target component A in chromatogram C2 is 7.14 minutes. The peak retention time of target component A in chromatogram C3 is 7.30 minutes. Although not shown, the table shown in FIG. 4 includes the peak retention times of 100 samples.

[0054] Next, the detection device 100 executes the detection program 130 for performing an abnormality detection processing. Fig. 5 is a flowchart showing the abnormality detection processing of the identification result. The processing steps shown in Fig. 5 are realized by the calculation device 101 executing the detection program 130.

[0055] The calculation device 101 detects whether or not there is an outlier among the multiple peak retention times shown in Fig. 4 (step S210). In the first embodiment, the calculation device 101 uses Hotelling's T 2 More specifically, the calculation device 101 calculates the peak retention time χ of all the samples of N number of samples (100 in the first embodiment) by i The calculation device 101 also calculates the average value μ of the peak retention times of all 100 samples. 2 Calculate the unbiased variance σ 2 is expressed by the following Equation 1.

[0056]

number

[0057] The calculation device 101 calculates the mean value μ and the unbiased variance σ 2 and the peak retention time χ i The abnormality degree a is calculated for each of the following equations.

[0058]

number

[0059] The calculation device 101 determines that the peak holding time is an outlier when the abnormality degree a of the peak holding time exceeds a predetermined threshold. The calculation device 101 determines that the peak holding time is not an outlier when the abnormality degree a of the peak holding time is equal to or less than the threshold. The threshold is, for example, 10.

[0060] 5, if there is no outlier (NO in step S220), the arithmetic device 101 ends the process. If there is an outlier (YES in step S220), the arithmetic device 101 detects the identification result corresponding to the outlier as abnormal data (step S230). The arithmetic device 101 highlights the abnormal data (step S240). More specifically, the arithmetic device 101 displays the peak retention time of the outlier on the display device 110, highlighting it more than other peak retention times different from the peak retention time of the outlier.

[0061] The calculation device 101 acquires a representative value based on the peak retention time different from the peak retention time of the outlier (step S250). The representative value is a value that represents normal values ​​that are not outliers, such as the average value of peak retention times different from the peak retention times of the outliers. Specifically, in the example of the first embodiment, if only the peak retention time of sample S3 is detected as an outlier, the average value of the peak retention times of the 99 samples other than sample S3 is calculated as the representative value. In the example of the first embodiment, the retention time "7.14 minutes", which is the same as the theoretical retention time, is calculated as the representative value. Thereafter, the calculation device 101 replaces the peak retention time of the outlier with the representative value (step S260).

[0062] FIG. 6 is a diagram showing an example of a chromatogram displayed after executing the flowchart of FIG. 5. As shown in FIG. 6, the calculation device 101 displays image P3C instead of the triangular image P3 showing the erroneous peak. Unlike image P3, image P3C is provided with color information. For example, image P3C is displayed in red. As described above, images P1 and P2 are white, so the red image P3C is displayed in an emphasized manner. This allows the detection device 100 to easily allow the user to recognize that the peak shown in image P3 was erroneous.

[0063] Furthermore, as shown in FIG. 6, using the representative value replaced in step S260, the calculation device 101 re-identifies peaks existing near the representative value as peaks of the target component A. FIG. 6 illustrates an image P3A showing peaks identified based on the representative value. Image P3A is displayed larger than images P1 and P2. This allows the detection device 100 to easily grasp the positions of peaks after the outliers have been replaced with the representative value. Furthermore, in the example of the first embodiment, an arrow-shaped image Ar1 is displayed, indicating the positions of both peaks before and after the outliers are replaced with the representative value. In this way, in the first embodiment, the arrow-shaped image Ar1 is displayed, allowing the user to easily grasp the positions of peaks before and after the outliers are replaced with the representative value.

[0064] 7 is a diagram showing an example of a table of peak information displayed after executing the flowchart of FIG. 5. As shown in FIG. 7, color information is added to the background of the cells indicating the peak retention times of chromatogram C3 in which an incorrect identification has been made. Specifically, in the table of FIG. 7, the background of the cell indicating the peak retention time "7.30 minutes" is red. This allows the detection device 100 to easily allow the user to recognize that the peak retention time "7.30 minutes" is the retention time of the incorrect peak.

[0065] In this way, the detection device 100 of the first embodiment can detect, as abnormal data, an identification result that has been erroneously identified using an outlier. Thus, in the first embodiment, the abnormal data is displayed to the user, prompting the user to correct the abnormal data, thereby enabling the peak in the chromatogram to be properly identified as the peak of the target component. Furthermore, as described above, the detection device 100 automatically replaces the outlier with a representative value, thereby enabling the peak in the chromatogram to be properly identified as the peak of the target component automatically, without requiring the user to perform any correction work. Furthermore, in the example of the first embodiment, an abnormality is determined based on whether or not the result is an outlier. This makes it possible to prevent discrepancies in the judgment of whether or not an identification result is abnormal, compared to when the presence or absence of an abnormality is determined by the user's visual inspection.

[0066] [Embodiment 2] In the first embodiment, an example was described in which peak retention time was used to determine the presence or absence of an outlier, and only one target component A in one sample was the subject of analysis. In the second embodiment, an example will be described in which the presence or absence of an outlier is determined using information other than peak retention time, and multiple target components are the subject of analysis. Note that in the second embodiment, the description of the configuration that overlaps with the configuration of the first embodiment will not be repeated.

[0067] In the second embodiment, the peak information used for outlier detection is the peak start retention time and the peak end retention time. As described above, the peak start retention time is the retention time when the signal intensity starts to rise, and the peak end retention time is the retention time when the signal intensity finishes falling. The peak start retention time and the peak end retention time are automatically detected by a peak detection algorithm that reads a chromatogram. More specifically, the detection device 100 detects as the "peak start retention time" the retention time at which the signal intensity increases from a state of signal intensity lower than a predetermined threshold and reaches a signal intensity equal to or greater than the predetermined threshold. The detection device 100 also detects as the "peak end retention time" the retention time at which the signal intensity decreases from a state of signal intensity higher than the predetermined threshold and reaches a signal intensity equal to or less than the predetermined threshold.

[0068] In the second embodiment, target component B is analyzed in addition to target component A. The theoretical retention time of target component B is "8.05 minutes." The theoretical peak start retention time of target component B is "8.01 minutes," and the theoretical peak end retention time is "8.09 minutes."

[0069] Fig. 8 is a diagram showing an example of a display of a chromatogram generated by the detection device 100 in embodiment 2. Similar to Fig. 3, Fig. 8 shows chromatograms C1, C2, and C3 corresponding to three samples S1, S2, and S3 out of 100 samples. Fig. 8 shows only the peak identified as target component A, and does not show the peak identified as target component B.

[0070] As shown in FIG. 8, in chromatogram C1, the signal intensity of the peak identified as target component A begins to rise at a retention time of 6.10 minutes and ends its decline at a retention time of 6.21 minutes. Image PS1 indicates that the peak start retention time of chromatogram C1 is 6.10 minutes. Image PE1 indicates that the peak end retention time of chromatogram C1 is 6.21 minutes. As shown in FIG. 8, the detection device 100 draws a baseline Bs1 in chromatogram C1 between the retention time at which the signal intensity starts to rise and the retention time at which the signal intensity ends its decline. The baseline Bs1 is a line used when calculating peak area and peak height, and is drawn by the detection device 100.

[0071] In chromatogram C2, the signal intensity of the peak identified as target component A begins to rise at a retention time of 6.11 minutes and ends its decline at a retention time of 6.23 minutes. Image PS2 shows that the peak start retention time of chromatogram C2 is 6.11 minutes. Image PE2 shows that the peak end retention time of chromatogram C2 is 6.23 minutes. As shown in FIG. 8, in chromatogram C2, a baseline Bs2 is drawn between the retention time at which the signal intensity begins to rise and the retention time at which the signal intensity ends its decline.

[0072] Furthermore, in chromatogram C3, the signal intensity of the peak identified as target component A begins to rise at a retention time of 6.11 minutes and ends its decline at a retention time of 6.34 minutes. Image PS3 shows that the peak start retention time of chromatogram C3 is 6.11 minutes. Image PE3 shows that the peak end retention time of chromatogram C2 is 6.34 minutes. As shown in Figure 8, in chromatogram C3, a baseline Bs3 is drawn between the retention time at which the signal intensity begins to rise and the retention time at which the signal intensity ends its decline.

[0073] In the second embodiment, sample S3 is contaminated with an impurity component whose peak occurs between retention times "6.25 minutes" and "6.35 minutes." Therefore, the detection device 100 detects the peak end retention time of the peak of target component A in chromatogram C3 as "6.34 minutes," which is relatively longer than that in chromatograms C1 and C2. This causes the detection device 100 to erroneously calculate the peak area of ​​target component A in chromatogram C3. In other words, the detection device 100 obtains an erroneous identification result for chromatogram C3.

[0074] 9 is a diagram showing an example of a peak information table according to the second embodiment. The detection apparatus 100 according to the second embodiment acquires, as peak information, the peak start retention time and peak end retention time of the peak of the target component A identified in each of the chromatograms C1 to C3. The detection apparatus 100 acquires the peak start retention time and peak end retention time of the identified peak using a peak detection algorithm, and generates the table shown in FIG. 9. The table shown in FIG. 9 is stored in the storage device 103, similar to FIG. 4.

[0075] As shown in FIG. 9, the peak start retention time of target component A in chromatogram C1 is retention time "6.10 minutes." The peak end retention time of target component A in chromatogram C1 is retention time "6.21 minutes." The peak start retention time of target component A in chromatogram C2 is retention time "6.11 minutes." The peak end retention time of target component A in chromatogram C2 is retention time "6.23 minutes." The peak start retention time of target component A in chromatogram C3 is retention time "6.11 minutes." The peak end retention time of target component A in chromatogram C3 is retention time "6.34 minutes."

[0076] As described above, the detection apparatus 100 of the second embodiment analyzes target component B in addition to target component A. The detection apparatus 100 of the second embodiment uses a peak detection algorithm to automatically identify peaks corresponding to target component B, as well as target component A, and generates the table shown in FIG. 9 from the identification results.

[0077] As shown in FIG. 9, the peak start retention time of target component B in chromatogram C1 is retention time "8.01 minutes." The peak end retention time of target component B in chromatogram C1 is retention time "8.09 minutes." The peak start retention time of target component B in chromatogram C2 is retention time "8.00 minutes." The peak end retention time of target component B in chromatogram C2 is retention time "8.08 minutes." The peak start retention time of target component B in chromatogram C3 is retention time "8.03 minutes." The peak end retention time of target component B in chromatogram C3 is retention time "8.08 minutes." In the example of FIG. 9, no abnormalities occurred in the identification results for target component B in chromatograms C1 to C3.

[0078] In the second embodiment, the detection device 100 also executes the flowchart of Fig. 5. In the second embodiment, the peak information that is the target for outlier detection is not the peak retention time, but the peak start retention time and the peak end retention time. Furthermore, in the second embodiment, two components, target components A and B, are used as target components, and therefore the flowchart of Fig. 5 is executed twice for one sample, one for each of target components A and B.

[0079] 10 is a diagram showing an example of a chromatogram displayed after executing the flowchart of FIG. 5 in the second embodiment. As shown in FIG. 10, the calculation device 101 displays an image PE3C in place of the triangular image PE3 that displayed an incorrect peak as the peak end retention time of the target component A. The image PE3C is displayed highlighted in red. This allows the detection device 100 in the second embodiment to make the user aware that the peak end retention time displayed in the image PE3 is incorrect.

[0080] Furthermore, as shown in FIG. 10, using the representative value replaced in step S260, the calculation device 101 re-identifies the peak end time existing near the representative value as the peak end time of target component A. FIG. 10 illustrates an image PE3A showing a peak identified based on the representative value. The image PE3A is displayed larger and more emphasized than the other triangular images. This allows the detection device 100 to easily grasp the peak end retention time after replacement with the representative value. Also, as shown in FIG. 10, the detection device 100 draws a baseline Bs3A based on the change in the peak end time based on the representative value. Furthermore, in the second embodiment, the arrow-shaped image Ar2 is displayed, allowing the user to easily grasp the position of the peak before and after replacement from the outlier with the representative value.

[0081] 11 is a diagram showing an example of a table of peak information displayed after executing the flowchart of FIG. 5 in the second embodiment. As shown in FIG. 11, color information is added to the background of the peak end retention time of chromatogram C3 where an incorrect identification has been made. Specifically, in the table of FIG. 11, the background of the cell of the peak retention time "6.34 minutes" is highlighted in red.

[0082] In addition, in the second embodiment, the above-mentioned Hotelling's T 211, the degree of anomaly calculated based on the method is displayed. As shown in Fig. 11, the degree of anomaly of the peak start retention time of target component A in chromatogram C1 is retention time "0.01", and the degree of anomaly of the peak end retention time of target component A in chromatogram C1 is retention time "0.04". Furthermore, the degree of anomaly of the peak start retention time of target component A in chromatogram C2 is retention time "0.03", and the degree of anomaly of the peak end retention time of target component A in chromatogram C2 is retention time "0.05".

[0083] Furthermore, the abnormality degree of the peak start retention time of target component A in chromatogram C3 is retention time "0.03," and the abnormality degree of the peak end retention time of target component A in chromatogram C3 is retention time "10.01." The detection device 100 determines that the peak end retention time of target component A in chromatogram C3, whose abnormality degree exceeds the threshold value "10," is abnormal.

[0084] In the second embodiment, the detection device 100 highlights the cell for the peak retention time of "6.34 minutes" as well as the cell for "Sample S3 (chromatogram C3)" and the cell for the abnormality level of "10.01" by coloring them red. This allows the user to easily determine which sample is abnormal and the degree of abnormality compared to other samples. If multiple outlier samples are detected, the detection device 100 may sort the display order by the degree of abnormality. This allows the user to view the samples in descending order of abnormality in the second embodiment.

[0085] In this way, in the second embodiment as well, an erroneous identification result is easily detected as an abnormality by using an outlier, and thus, in the second embodiment as well, a peak in a chromatogram can be appropriately identified as a peak of the target component.

[0086] <Modification> Hereinafter, other embodiments that are partial modifications of the above-described embodiment will be described.

[0087] In the above example, the peak information includes the peak retention time, peak start retention time, peak end retention time, peak area, and the like. However, the information included in the peak information is not limited to these. In one aspect, the peak information includes the period from the peak start retention time to the peak end retention time (also referred to as the "peak width"), the period from the peak start retention time to the peak retention time (also referred to as the "first half of the peak width"), the period from the peak retention time to the peak end retention time (also referred to as the "second half of the peak width"), the magnitude of the signal intensity when the signal intensity starts to rise (also referred to as the "peak start height"), and the magnitude of the signal intensity when the signal intensity finishes falling (also referred to as the "peak end height"). Furthermore, the peak information may include the peak width, first half of the peak width, and second half of the peak width at a predetermined intensity (N%). It may also include the degree of separation from adjacent peaks, or a separation factor, retention factor, theoretical plate number indicating column efficiency, symmetry factor indicating the degree of symmetry of the peak, and the like.

[0088] In the example above, Hotelling's T 2 In the above method, an example in which the threshold value is "10" has been described, but the threshold value may be a number other than "10." For example, the threshold value may be "5," "20," or "30," and may be determined based on experiments.

[0089] In the example of the first embodiment, the peak retention time is used as the peak information and is the target of outlier detection. However, the peak information that is the target of outlier detection may be other peak information described above, or may be, for example, the difference between the peak retention time and the theoretical retention time.

[0090] In the above example, a shipment of agricultural products is used as an example of a sample. However, a standard sample prepared in advance may be used as the sample, for example, to generate a calibration curve for identifying a target component from peak information. In other words, some of the multiple samples may not be actual samples such as agricultural products actually shipped to the market, but may be standard samples into which the target component has been artificially mixed in order to obtain information on the target component.

[0091] In the above example, the Hotelling T method is used to detect outliers. 2 However, in some aspects, outliers may be detected by other methods, such as simply using the variance or the distance from the mean, or using the k-nearest neighbor method.

[0092] In the above example, image highlighting was described as a method of displaying image P3C with color information and enlarging image P3A. However, other methods of highlighting images may be used, such as blinking the image or changing the image shape from a triangular shape. Also, in the above example, only the outliers before being replaced with the representative value were displayed in the tables of FIGS. 7 and 11. However, the outliers may also be displayed together with the representative value. Furthermore, in the above example, red color information was assigned when the abnormality level exceeded the threshold value "10." However, color information may be assigned in stages depending on the abnormality level. That is, the detection device 100 may assign yellow color information when the abnormality level exceeds the threshold value "5" but is equal to or less than the threshold value "10," and may assign red color information when the abnormality level exceeds the threshold value "10."

[0093] [Aspect] It will be appreciated by those skilled in the art that the exemplary embodiments described above are examples of the following aspects.

[0094] (Section 1) A detection device according to one aspect includes: an acquisition unit that acquires a plurality of pieces of detection data corresponding to a plurality of samples detected by a chromatograph; a calculation unit that processes the plurality of pieces of detection data acquired by the acquisition unit, the calculation unit acquires an identification result indicating that peak information of signal intensity extracted from each of the plurality of detection data has been identified as peak information of signal intensity corresponding to a target component; If outlier peak information exists among the plurality of peak information identified in each of the plurality of detection data, it is detected that the identification result corresponding to the outlier peak information is abnormal.

[0095] According to the detection device 100 described in paragraph 1, peaks in a chromatogram can be appropriately identified as peaks of the target component.

[0096] (Section 2) In the detection device 100 described in paragraph 1, the calculation unit displays the peak information of the outlier on the display device so as to emphasize the peak information of the outlier more than other peak information different from the peak information of the outlier.

[0097] According to the detection device described in paragraph 2, it is possible to make the user aware that the identified peak was incorrect.

[0098] (Section 3) In the detection device 100 according to the first or second aspect, the calculation unit obtaining a representative value based on peak information different from the peak information of the outlier; The peak information of the outliers is replaced with the representative value.

[0099] According to the detection device described in paragraph 3, outliers can be replaced with representative values ​​that are representative of normal values.

[0100] (Section 4) In the detection device 100 described in paragraph 3, the calculation unit displays on the display device in a recognizable manner both the peak information of the outlier before replacing it with the representative value and the peak information after replacement.

[0101] According to the detection device described in paragraph 4, it is possible to allow the user to easily grasp the positions of the peaks before and after the outliers are replaced with the representative values.

[0102] (Section 5) In the detection device 100 described in any one of paragraphs 1 to 4, the peak information includes the retention time when the signal intensity is at a maximum value.

[0103] According to the detection device described in item 5, it is possible to detect an abnormality in identification using peak retention time.

[0104] (Section 6) In the detection device 100 described in any one of paragraphs 1 to 5, the peak information includes at least one of the retention time when the signal intensity starts to rise, the retention time when the signal intensity finishes falling, and the position of the baseline.

[0105] According to the detection device described in item 6, it is possible to detect an abnormality in identification using the peak start retention time or the peak end retention time.

[0106] (Section 7) In the detection device 100 described in any one of paragraphs 1 to 6, the calculation unit corrects in advance the retention time included in each of the plurality of detection data.

[0107] According to the detection device described in item 7, fluctuations in retention time due to column deterioration or the like can be corrected in advance.

[0108] (Section 8) In the detection device 100 according to any one of items 1 to 7, the detection device is 2A method is used to determine whether or not the outlier peak information exists among the plurality of peak information.

[0109] According to the detection device described in paragraph 8, Hotelling's T 2 The method can be used to determine outliers. (Section 9) In the detection device 100 described in any one of paragraphs 1 to 8, the plurality of samples include a standard sample for generating information for identifying the target component from the peak information.

[0110] According to the detection device described in item 9, it is possible to detect identified abnormalities using a standard sample.

[0111] (Section 10) In one embodiment, a detection method is provided in which a computer detects an abnormality in an identification result of a target component, the detection method comprising: acquiring a plurality of detection data corresponding to each of a plurality of samples detected by a chromatograph; and processing the plurality of pieces of detection data acquired by the acquiring step, The processing step includes: acquiring an identification result indicating that peak information of signal intensity extracted from each of the plurality of detection data has been identified as peak information of signal intensity corresponding to a target component; and if outlier peak information is present among the plurality of peak information identified in each of the plurality of detection data, detecting that the identification result corresponding to the outlier peak information is abnormal.

[0112] According to the detection method described in item 10, a peak in a chromatogram can be appropriately identified as a peak of a target component.

[0113] (Section 11) In one aspect, a detection program for detecting an abnormality in an identification result of a target component includes: acquiring a plurality of detection data corresponding to each of a plurality of samples detected by a chromatograph; and processing the plurality of pieces of detection data acquired by the acquiring step, The processing step includes: acquiring an identification result indicating that peak information of signal intensity extracted from each of the plurality of detection data has been identified as peak information of signal intensity corresponding to a target component; and when outlier peak information is present among the plurality of peak information identified in each of the plurality of detection data, detecting that the identification result corresponding to the outlier peak information is abnormal.

[0114] According to the detection program described in item 11, peaks in a chromatogram can be appropriately identified as peaks of a target component.

[0115] (Section 12) In one aspect, the detection system includes: Chromatography and a detection device that detects an abnormality in the identification result of the target component; The detection device includes an acquisition unit that acquires a plurality of pieces of detection data corresponding to each of a plurality of samples detected by the chromatograph; a calculation unit that processes the plurality of pieces of detection data acquired by the acquisition unit, The calculation unit obtaining an identification result indicating that peak information of signal intensity extracted from each of the plurality of detection data has been identified as peak information of signal intensity corresponding to a target component; A detection system that, when outlier peak information is present among the multiple peak information identified in each of the multiple detection data, detects that the identification result corresponding to the outlier peak information is abnormal.

[0116] According to the detection system described in paragraph 12, peaks in a chromatogram can be appropriately identified as peaks of the target component.

[0117] The embodiments disclosed herein should be considered to be illustrative in all respects and not restrictive. The scope of the present invention is defined by the claims, not by the description of the above embodiments, and is intended to include all modifications within the meaning and scope of the claims. [Explanation of symbols]

[0118] 1 detection system, 10 chromatograph, 11 container, 12 liquid pump, 13 injector, 14 column, 15 detector, 100 detection device, 101 computing device, 102 memory, 103 storage device, 104 interface, 110 display device, 120 input device, 130 detection program, 135 acquisition program, A, B target components, Ar1, Ar2, P1 to P3, P3A, PS1 to PS3, PE1 to PE3, PE3C, PE3A images, C1 to C3 chromatograms, S1 to S3 samples, baseline Bs1 to Bs3, Bs3A.

Claims

1. an acquisition unit that acquires a plurality of pieces of detection data corresponding to the plurality of samples detected by the chromatograph; a calculation unit that processes the plurality of detection data acquired by the acquisition unit, The calculation unit is obtaining an identification result indicating that the peak information of the signal intensity extracted from each of the plurality of detection data has been identified as the peak information of the signal intensity corresponding to the target component; A detection device that detects that, when outlier peak information is present among the multiple peak information identified in each of the multiple detection data, the identification result corresponding to the outlier peak information is abnormal.

2. The detection device according to claim 1 , wherein the calculation unit causes the display device to display the outlier peak information in a manner that emphasizes the outlier peak information more than other peak information different from the outlier peak information.

3. The calculation unit is A representative value is obtained based on peak information other than the peak information of the outlier. The detection apparatus according to claim 1 , wherein peak information of the outlier is replaced with the representative value.

4. The detection device according to claim 3 , wherein the calculation unit causes a display device to display both the peak information before replacing the peak information of the outlier with the representative value and the peak information after the replacement in a recognizable manner.

5. 5. The detection device according to claim 1, wherein the peak information includes a retention time when the signal intensity is at a maximum value.

6. The detection device according to any one of claims 1 to 4, wherein the peak information includes at least one of a retention time when the signal intensity starts to rise, a retention time when the signal intensity stops to fall, and a baseline position.

7. 5. The detection device according to claim 1, wherein the calculation unit performs a correction in advance for a retention time included in each of the plurality of detection data.

8. The detection device is a Hotelling T ２ 5. The detection device according to claim 1, further comprising: a method for determining whether or not the outlier peak information is present among the plurality of peak information.

9. 5. The detection apparatus according to claim 1, wherein the plurality of samples includes a standard sample for generating information for identifying the target component from the peak information.

10. A detection method in which a computer detects an abnormality in an identification result of a target component, comprising: acquiring a plurality of detection data corresponding to each of a plurality of samples detected by a chromatograph; and processing the plurality of detection data acquired by the acquiring step; The processing step includes: acquiring an identification result indicating that the peak information of the signal intensity extracted from each of the plurality of detection data has been identified as the peak information of the signal intensity corresponding to the target component; and when outlier peak information is present among the multiple peak information identified in each of the multiple detection data, detecting that the identification result corresponding to the outlier peak information is abnormal.

11. A detection program for detecting an abnormality in an identification result of a target component, On the computer, acquiring a plurality of detection data corresponding to each of a plurality of samples detected by a chromatograph; and processing the plurality of pieces of detection data acquired by the acquiring step. The processing step includes: acquiring an identification result indicating that the peak information of the signal intensity extracted from each of the plurality of detection data has been identified as the peak information of the signal intensity corresponding to the target component; and when outlier peak information is present among the multiple peak information identified in each of the multiple detection data, detecting that the identification result corresponding to the outlier peak information is abnormal.

12. Chromatography and a detection device for detecting an abnormality in the identification result of the target component; The detection device includes: an acquisition unit that acquires a plurality of detection data corresponding to each of a plurality of samples detected by the chromatograph; a calculation unit that processes the plurality of detection data acquired by the acquisition unit, The calculation unit is obtaining an identification result indicating that the peak information of the signal intensity extracted from each of the plurality of detection data has been identified as the peak information of the signal intensity corresponding to the target component; A detection system that detects that, when outlier peak information is present among the multiple peak information identified in each of the multiple detection data, the identification result corresponding to the outlier peak information is abnormal.

Images