Capillary electrophoresis apparatus, analysis method and program

Abstract

To provide a capillary electrophoresis apparatus, an analysis method, and a program that facilitate tracking of the course of a chemical reaction.SOLUTION: A capillary electrophoresis apparatus 1 comprises: an electrophoresis section 20 that electrophoreses a sample in a detection target portion 262 of a capillary 26;, a light source 32 that irradiates the sample with light; and a detector 348 having a plurality of light receiving sections 3482 provided at respective detection positions DP aligned in the extension direction of the capillary 26, and detecting the intensity of light emitted from the detection target portion 262 at each of a plurality of time points using each of the plurality of light receiving sections 3482.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present disclosure relates to a capillary electrophoresis apparatus, an analysis method, and a program. [Background technology]

[0002] Conventionally, there are known techniques for analyzing chemical reactions using a capillary electrophoresis device. For example, Patent Document 1 and Patent Document 2 disclose a technique for measuring the mobility of each sample substance contained in a sample using a capillary electrophoresis device, and determining the binding constant of a reaction between substances based on the mobility of each sample substance obtained by the measurement. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Patent Publication No. 2011-55741 [Patent Document 2] Patent Publication No. 2005-43284 Summary of the Invention [Problem to be solved by the invention]

[0004] However, with the configuration of the conventional capillary electrophoresis device, it is difficult to track the process of a chemical reaction. Specifically, in the conventional capillary electrophoresis device, the sample substance is detected only at a fixed point of the capillary, so that only information at the time when the fixed point is reached can be obtained for each sample substance. For example, in a system in which two types of substances A1 and A2 react with substance B in competition with each other, it is difficult to obtain information on which of substances A1 and A2 is more likely to react with substance B, or information on reaction intermediates temporarily generated before the fixed point is reached.

[0005] An object of the present disclosure is to provide a capillary electrophoresis apparatus, an analysis method, and a program that make it easy to track the course of a chemical reaction. [Means for solving the problem]

[0006] The capillary electrophoresis device according to the present disclosure comprises an electrophoresis section for electrophoresing a sample in a detection target portion of a capillary, a light source for irradiating light onto the sample, and a detector having a plurality of light receiving sections respectively provided at a plurality of detection positions aligned along the extension direction of the capillary, and detecting the intensity of light emitted from the detection target portion at each of a plurality of time points using each of the plurality of light receiving sections. [Brief description of the drawings]

[0007] [Figure 1] 1 is a diagram showing an example of the overall configuration of a capillary electrophoresis apparatus according to an embodiment of the present invention. [Diagram 2] FIG. 2 is an enlarged view of the periphery of a measurement unit in FIG. [Diagram 3] FIG. 2 is a diagram illustrating an example of a configuration of a detector. [Figure 4] FIG. 2 is a functional block diagram showing an example of functions realized by the information processing device. [Diagram 5] 5A to 5C are diagrams illustrating an example of measurement data, light intensity distribution data, and spectrum data. [Figure 6] FIG. 11 is a diagram illustrating an example of a function of an association unit. [Figure 7] FIG. 2 is an enlarged view of a detection target portion. [Figure 8] 10 is a diagram illustrating an example of a function of a mobility calculation unit; [Figure 9] 11 is a diagram illustrating an example of a function of a separation time point identifying unit. FIG. [Figure 10] FIG. 2 is a flow chart showing an example of an analytical method by capillary electrophoresis according to the present embodiment. [Figure 11] FIG. 11 is a flowchart illustrating an example of a process performed by an association unit. [Figure 12] 11 is a flowchart showing an example of a process of a mobility calculation unit. FIG. [Figure 13A] FIG. 11 is a flow chart illustrating an example of a process of a separation time point identifying unit. [Figure 13B]FIG. 11 is a flow chart illustrating an example of a process of a separation time point identifying unit. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0008] Hereinafter, embodiments of the present disclosure will be described in detail with reference to the drawings.

[0009] [1. Overall configuration of capillary electrophoresis device 1] Fig. 1 is a diagram showing an example of the overall configuration of a capillary electrophoresis apparatus 1 according to this embodiment. Fig. 2 is an enlarged view showing the periphery of a measurement unit 30 in Fig. 1. As shown in Fig. 1, the capillary electrophoresis apparatus 1 includes an information processing device 10, an electrophoresis unit 20, and a measurement unit 30.

[0010] [1-1. Information processing device 10] The information processing device 10 is, for example, a known computer system. The information processing device 10 includes a control unit, a storage unit, a display unit, and an input unit. The control unit includes at least one processor. The storage unit includes a main storage unit such as a random access memory (RAM) and an auxiliary storage unit capable of statically recording information such as a hard disk drive (HDD) and a solid state drive (SSD). The storage unit stores an analysis program using capillary electrophoresis according to the present embodiment, and the control unit executes this program to realize the device, function, and method according to the present embodiment. The storage unit may also store information (such as molecular weight and spectral data) of each substance contained in the sample. The display unit is a display device that displays the analysis results by the control unit. The display unit displays, for example, light intensity distribution data ID and spectral data SD, which will be described later. The input unit is a device for a user to input information, such as a keyboard, a mouse, or a touch panel.

[0011] Next, the electrophoresis section 20 and the measurement section 30 will be described with reference to FIG.

[0012] [1-2. Electrophoresis section 20] The electrophoresis unit 20 electrophoreses the sample in the detection target portion 262 of the capillary 26. The electrophoresis unit 20 includes a power source 22, liquid tanks 24a and 24b, and a capillary 26. The power source 22 is, for example, a high-voltage power source with an output of 0 to ±30 kV, and is connected via wiring to liquid tanks 24a and 24b filled with an electrophoretic liquid. One end of the capillary 26 is immersed in the electrophoretic liquid filled in the liquid tank 24a, and the other end of the capillary 26 is immersed in the electrophoretic liquid filled in the liquid tank 24b. The capillary 26 itself is filled with the electrophoretic liquid. The electrophoresis section 20 introduces a sample to the base end 2622 of the detection target portion 262 of the capillary 26 using a pump or the like (not shown), and then applies a voltage to both ends of the capillary 26 using the power source 22, causing the introduced sample to electrophorese from the base end 2622 to the end 2624 of the detection target portion 262 (see Figure 2).

[0013] More specifically, the electrophoresis unit 20 electrophoreses one or more sample substances SM contained in the sample and one or more product substances PM derived from at least one of the one or more sample substances SM in the detection target portion 262 of the capillary 26 (see FIG. 2). Specifically, the product substances PM are one or more substances generated by at least one chemical reaction of the one or more sample substances SM. In this specification, a chemical reaction refers to a process in which one or more substances change into one or more other substances, and also includes a process in which one or more substances change into one or more other substances without the creation or cleavage of chemical bonds (for example, protein-protein interaction driven by the hydrophobic effect).

[0014] [1-3.Measurement part 30] The measurement unit 30 includes a light source 32 and a spectroscopic detector 34 .

[0015] [1-3-1.Light source 32] The light source 32 irradiates the sample with light. In this embodiment, the light source 32 continues to continuously irradiate the sample with light while the sample is undergoing electrophoresis in the detection target portion 262. The light source 32 may continue to intermittently irradiate the sample with light while the sample is undergoing electrophoresis in the detection target portion 262. In this embodiment, the light source 32 is a non-coherent light source. For example, a deuterium lamp or a tungsten lamp may be used as the light source 32.

[0016] [1-3-2.Spectroscopic detector 34] The spectroscopic detector 34 includes a housing 341, a lens 342, a slit 344, a spectroscope 346, and a detector 348. The housing 341 accommodates the lens 342, the slit 344, the spectroscope 346, and the detector 348. The lens 342 collects the light emitted from the detection target portion 262 toward the slit 344. The light emitted from the slit 344 is dispersed by the spectroscope 346 and then detected by the detector 348. The spectroscope 346 and the detector 348 will be described in detail below.

[0017] The spectroscope 346 separates the light emitted from the detection target portion 262 into a plurality of wavelength components. In this embodiment, the spectroscope 346 separates the light emitted from the slit 344 into a plurality of wavelength components. As the spectroscope 346, various known spectroscopes can be used. Although FIG. 2 illustrates an example in which the spectroscope 346 is a concave diffraction grating, the spectroscope 346 is not limited to this example and may be, for example, a Czerny-Turner type spectroscope or a transmission type spectroscope.

[0018] 3 is a diagram showing an example of the configuration of the detector 348. The detector 348 has a plurality of light receiving parts 3482 provided at a plurality of detection positions DP aligned in a first direction D1, and detects the intensity of light emitted from the detection target portion 262 at a plurality of time points by each of the plurality of light receiving parts 3482. Here, the first direction D1 is a direction along the extension direction of the capillary 26.

[0019] The light receiving unit 3482 provided at each of the multiple detection positions DP detects the intensity of light for each wavelength component separated by the spectroscope 346. Specifically, each light receiving unit 3482 includes multiple light receiving elements PD arranged along the second direction D2, and each light receiving element PD included in each light receiving unit 3482 detects the intensity of light for each wavelength component. Here, the second direction D2 is the direction in which light is separated by the spectroscope 346. The second direction D2 is a direction perpendicular to the first direction D1. For example, a photodiode may be used as the light receiving element PD. That is, a known photodiode array detector may be used as the detector 348.

[0020] [1-5.Summary] In the capillary electrophoresis apparatus 1 described above, a plurality of light receiving parts 3482 are provided at each of a plurality of detection positions DP aligned along the extension direction of the capillary 26. Each of the plurality of light receiving parts 3482 detects the intensity of light emitted from the detection target portion 262 at each time point. This makes it possible to obtain data (light intensity distribution data ID, described later) indicating where each substance contained in the sample is present in the detection target portion 262 at each time point.

[0021] Furthermore, according to the capillary electrophoresis device 1, since each light receiving part 3482 detects the light intensity for each wavelength component, it is possible to obtain spectrum information (spectrum data SD described later) for each detection position DP. That is, it is possible to obtain spectrum information of the sample substance SM or the product substance PM.

[0022] 2. Functions Realized by Information Processing Device 10 Next, functions realized by the information processing device 10 will be described. Fig. 4 is a functional block diagram showing an example of functions realized by the information processing device 10. In the information processing device 10, a light intensity distribution data acquisition unit 100, a spectrum data acquisition unit 102, an association unit 104, a mobility calculation unit 106, and a deviation time point identification unit 108 are realized. The light intensity distribution data acquisition unit 100, the spectrum data acquisition unit 102, the association unit 104, the mobility calculation unit 106, and the deviation time point identification unit 108 are realized mainly by a control unit of the information processing device 10.

[0023] First, the light intensity distribution data acquiring unit 100 and the spectrum data acquiring unit 102 will be described with reference to Fig. 5. Fig. 5 is a diagram showing an example of measurement data MD, light intensity distribution data ID, and spectrum data SD. Fig. 5 illustrates an example of a case where a single molecule reaction in which molecule B is produced from molecule A is analyzed by the capillary electrophoresis device 1. In this case, molecule A corresponds to the sample substance SM, and molecule B corresponds to the product substance PM. Note that the number of sample substances SM and the number of product substances PM are not limited to this example, and each may be two or more.

[0024] [2-1. Light intensity distribution data acquisition unit 100] The light intensity distribution data acquiring section 100 acquires light intensity distribution data ID based on measurement data MD, which are the detection results of the detector 348 at each of a plurality of time points.

[0025] The measurement data MD relating to each of the multiple time points has position information P, wavelength information W, and light intensity information I (see FIG. 5). The position information P is information indicating the position of the detection target portion 262 corresponding to each of the multiple light receiving units 3482. The wavelength information W is information indicating the wavelength component of the light detected by each light receiving element PD included in each light receiving unit 3482. The light intensity information I is information indicating the intensity of the light (each wavelength component) detected by each light receiving element PD included in each light receiving unit 3482.

[0026] It can also be said that the measurement data MD relating to each of the multiple time points is a spectroscopic image obtained by capturing an image of the detection target portion 262 at each of the multiple time points. In other words, it can also be said that the spectroscopic detector 34 acquires a spectroscopic image having the detection target portion 262 as a subject at each of the multiple time points. Therefore, a known spectroscopic camera such as a hyperspectral camera may be used as the spectroscopic detector 34 itself.

[0027] The light intensity distribution data ID indicates the distribution of the light intensity of a predetermined wavelength component λ in the detection target portion 262 among the multiple wavelength components detected by each of the multiple light receiving units 3482 for each of multiple time points (see FIG. 5). The light intensity distribution data ID also indicates one or more positions at which one or more detection target substances, which are one or more sample substances SM or one or more generated substances PM contained in the sample, exist. The light intensity distribution data ID can also be said to be a diagram in which a value corresponding to the light intensity of the predetermined wavelength component λ is plotted against the position (distance from the base end 2622) of the detection target portion 262. In this embodiment, the light intensity distribution data ID indicates the absorbance of the detection target portion 262 at a position corresponding to each light receiving unit 3482. That is, in this embodiment, the light intensity distribution data ID is a diagram in which the absorbance is plotted against the position of the detection target portion 262, and has absorbance peaks that indicate one or more positions at which one or more detection target substances exist.

[0028] The light intensity distribution data ID is not limited to one indicating absorbance, and may be one indicating, for example, fluorescence intensity. In this case, the light source 32 may irradiate light having an excitation wavelength of the target fluorescent substance. Also, instead of irradiating the detection target portion 262 with light, the sample may be irradiated with light before the start of electrophoresis. Furthermore, the light source 32 may be a coherent light source such as a laser.

[0029] In the example shown in FIG. 5, the light intensity distribution data acquisition unit 100 acquires light intensity distribution data ID1 and light intensity distribution data ID2. The light intensity distribution data ID1 is obtained at a time t i In FIG. 1, the light intensity distribution data ID1 indicates a position x1 where molecule A exists and a position x2 where molecule B exists. Specifically, the light intensity distribution data ID1 has absorbance peaks at positions x1 and x2. The light intensity distribution data ID2 indicates a position at time t j In FIG. 1, the light intensity distribution data ID2 indicates a position x3 where molecule A exists and a position x4 where molecule B exists. Specifically, the light intensity distribution data ID2 has absorbance peaks at positions x3 and x4. The peaks at positions x1 and x3 correspond to molecule A, and the peaks at positions x2 and x4 correspond to molecule B.

[0030] [2-2. Spectral data acquisition unit 102] The spectral data acquisition unit 102 acquires first spectral data SD1 and second spectral data SD2 based on the measurement data MD relating to each of the multiple time points. The first spectral data SD1 indicates the spectrum of light detected by the light receiving unit 3482 corresponding to one or more positions indicated by the light intensity distribution data ID relating to a first time point among the multiple time points. The second spectral data SD2 indicates the spectrum of light detected by the light receiving unit 3482 corresponding to one or more positions indicated by the light intensity distribution data ID relating to a second time point among the multiple time points. In this embodiment, a case will be illustrated in which the first spectral data SD1 and the second spectral data SD2 are absorption spectral data.

[0031] 5, the spectrum data acquiring unit 102 acquires first spectrum data SD1a. The first spectrum data SD1a indicates the spectrum of light detected by the light receiving unit 3482 corresponding to the position x1 indicated by the light intensity distribution data ID1. Similarly, the spectrum data acquiring unit 102 acquires first spectrum data SD1b. The first spectrum data SD1b indicates the spectrum of light detected by the light receiving unit 3482 corresponding to the position x2 indicated by the light intensity distribution data ID1.

[0032] The spectral data acquiring unit 102 also acquires second spectral data SD2a. The second spectral data SD2a indicates the spectrum of light detected by the light receiving unit 3482 corresponding to the position x3 indicated by the light intensity distribution data ID2. Similarly, the spectral data acquiring unit 102 acquires second spectral data SD2b. The second spectral data SD2b indicates the spectrum of light detected by the light receiving unit 3482 corresponding to the position x4 indicated by the light intensity distribution data ID2.

[0033] That is, in the example of FIG. 5, the first spectral data SD1a and the second spectral data SD2a represent the absorption spectrum of molecule A, and the first spectral data SD1b and the second spectral data SD2b represent the absorption spectrum of molecule B.

[0034] The light intensity distribution data ID acquired by the light intensity distribution data acquiring unit 100 and the spectrum data SD acquired by the spectrum data acquiring unit 102 described above are subjected to processing in an associating unit 104, a mobility calculating unit 106, and a separation time point identifying unit 108, which will be described later. After acquiring the light intensity distribution data ID and the spectrum data SD, an experimenter may of course perform analysis based on these data.

[0035] [2-3. Association unit 104] Next, the associating unit 104 will be described. Fig. 6 is a diagram for explaining an example of the function of the associating unit 104. Fig. 6 illustrates an example in which a system in which molecules A1 and A2 compete with each other to react with molecule B is analyzed by the capillary electrophoresis device 1. In Fig. 6, peaks corresponding to reaction products are omitted for the sake of simplicity.

[0036] The associating unit 104 associates at least one of the one or more positions of the light intensity distribution data ID relating to the first time point with any of the one or more positions indicated by the light intensity distribution data ID relating to the second time point, based on the first spectral data SD1 and the second spectral data SD2.

[0037] For example, the associating unit 104 may associate the position x 11 Spectral data SD (hereinafter, simply referred to as "position x") indicating the spectrum of light detected by the light receiving unit 3482 corresponding to 11 The spectral data of the X-ray diffraction pattern is called "SD". 21 Spectral data SD (hereinafter, simply referred to as "position x") indicating the spectrum of light detected by the light receiving unit 3482 corresponding to 21 Based on the spectrum data SD of the light intensity distribution data ID at the time t1,11 The position x of the light intensity distribution data ID corresponding to the time t2 21 Associate with.

[0038] Specifically, the associating unit 104 11 The spectrum data SD and the position x 21 The spectral data SD of and the light intensity distribution data ID at the time t1 are calculated according to the similarity. 11 The position x of the light intensity distribution data ID corresponding to the time t2 21 For example, the associating unit 104 associates the position x 21 The spectrum data SD and the position x 21 It is determined whether the similarity between the spectrum data SD of and is equal to or greater than a predetermined threshold, and if the similarity is equal to or greater than the predetermined threshold, the position x 11 The position x of the light intensity distribution data ID corresponding to the time t2 21 Associate with.

[0039] More specifically, the associating unit 104 11 The spectrum data SD and the position x 21 The spectral data SD of and the light intensity distribution data ID at the time t1 are calculated according to the similarity. 11 and the position x of the light intensity distribution data ID relating to time t2 21 For example, the associating unit 104 assigns the same label to the position x 11 and the position x of the light intensity distribution data ID relating to time t2 21 In addition, the associating unit 104 displays the component name (A1) at the position x 11 The position x of the light intensity distribution data ID corresponding to the peak and time t2 21 The peaks appearing in the graph may be displayed in the same color.

[0040] According to the associating unit 104 described above, it becomes easy to track the process of a chemical reaction. For example, as shown in Fig. 6, in a system in which two kinds of molecules A1 and A2 compete with each other to react with molecule B, it is easy to grasp which of molecules A1 and A2 reacts more easily with molecule B. In the example of Fig. 6, since the peak corresponding to molecule A1 overtakes the peak corresponding to molecule A2 midway, it is estimated that molecule A1 reacts more easily with molecule B than molecule A2.

[0041] [2-4. Mobility calculation unit 106] The mobility calculation unit 106 will now be described. FIG. 7 is an enlarged view of the detection target portion 262. FIG. 8 is a view for explaining an example of the function of the mobility calculation unit 106. FIG. 8 illustrates an example in which a bimolecular reaction in which molecule A reacts with molecule B to generate molecule AB is analyzed by the capillary electrophoresis device 1. Note that, in FIG. 8, for the sake of simplicity, the peaks corresponding to molecule B and molecule AB are omitted from illustration.

[0042] The mobility calculation unit 106 calculates at least one mobility μ of one or more detection target substances in each of multiple sections S (see Figure 7) of the detection target portion 262 based on the light intensity distribution data ID relating to at least a portion of the multiple time points.

[0043] 8, the mobility calculation unit 106 calculates the mobility μ of molecule A in each of multiple sections S1, S2, S3, and S4 based on the light intensity distribution data ID for each of the times t0, t1, t2, and t3. Here, section S1 is the distance from position x0 to position x1, section S2 is the distance from position x1 to position x2, section S3 is the distance from position x2 to position x3, and section S4 is the distance from position x3 to position x4.

[0044] Specifically, the mobility calculation unit 106 identifies positions x0, x1, x2, x3, and x4 at which molecule A exists, which are indicated by the light intensity distribution data ID for each of the time points t0, t1, t2, and t3, and calculates the mobility μ of molecule A in each of the multiple sections S1, S2, S3, and S4 based on each of the time points t0, t1, t2, and t3 and each of the positions x0, x1, x2, x3, and x4. Note that the above-mentioned spectrum data SD or a standard substance may be used to identify the position of molecule A, that is, to identify the peak corresponding to molecule A.

[0045] The mobility calculation unit 106 calculates the mobility μ based on, for example, the following equation 1. In the following equation 1, l is the migration distance, E is the electric field strength, and t is the measurement time point.

[0046]

number

[0047] In the example shown in Fig. 8, the mobility μ of molecule A is the same in all of the sections S1, S2, S3, and S4. The fact that the mobility μ of molecule A does not change across multiple sections in this way indicates that the reaction to be analyzed is a one-step reaction in which one molecule A reacts with one molecule B in a one-to-one relationship.

[0048] On the other hand, unlike the example shown in FIG. 8, for example, when the mobility μ of molecule A gradually increases over multiple sections, the reaction to be analyzed is presumed to be a multi-step reaction in which one molecule A reacts with one molecule B to produce molecule AB, and then molecule AB and molecule B further react to produce molecule AB2.

[0049] That is, the mobility calculation unit 106 calculates the mobility μ of the detection target substance in each of the multiple sections, and thus it is possible to know whether the mobility μ of the detection target substance increases, decreases, or remains constant as the section progresses. This makes it possible to estimate the reaction mechanism of the reaction to be analyzed. That is, the mobility calculation unit 106 makes it possible to estimate whether the reaction to be analyzed is a one-step reaction or a multi-step reaction.

[0050] [2-5. Separation time determination unit 108] The separation time identifying unit 108 will be described. Fig. 9 is a diagram illustrating an example of the function of the separation time identifying unit 108. Fig. 9 illustrates a case in which molecule B is isolated from a mixture containing molecules A, B, and C and analyzed by the capillary electrophoresis apparatus 1.

[0051] The separation time identifying unit 108 identifies, among the multiple time points, the earliest time point at which the position of a first substance, which is one of the one or more detection target substances, and the position of a second substance, which is another one of the one or more detection target substances, are observed separated from each other, based on the light intensity distribution data ID corresponding to at least a part of the multiple time points, when the electrophoresis unit 20 electrophoreses the test sample (first sample) in the detection target portion 262 of the capillary 26. In this embodiment, the case where the test sample is a mixture containing the above-mentioned molecule A, molecule B, and molecule C is illustrated as an example.

[0052] 9, among multiple time points t0, t1, t2, and t3, the earliest time point at which the position of molecule A and the position of molecule B are observed to be separated is time point t3. Therefore, the separation time point identifying unit 108 identifies time point t3 as the separation time point.

[0053] The separation time point identifying unit 108, for example, i In the light intensity distribution data ID corresponding to (i=0, 1, 2, 3), it is determined whether or not the peak corresponding to molecule A and the peak corresponding to molecule B are separated. If it is determined that the peak corresponding to molecule A and the peak corresponding to molecule B are separated, iOn the other hand, when the separation time identifying unit 108 determines that the peak corresponding to molecule A and the peak corresponding to molecule B are not separated, it identifies the time t i The next point in time, t i+1 In the light intensity distribution data ID relating to the above, it is determined whether or not the peak corresponding to molecule A and the peak corresponding to molecule B are separated, and the process is repeated until the point in time when they are separated is identified.

[0054] The determination of whether the peak corresponding to molecule A and the peak corresponding to molecule B are separated may be made, for example, by determining whether the area of ​​overlap between the peak corresponding to molecule A and the peak corresponding to molecule B is equal to or less than a predetermined threshold, or by determining whether the distance between the position of the peak corresponding to molecule A and the position of the peak corresponding to molecule B is equal to or more than a predetermined threshold.

[0055] In addition, each peak may be identified using the above-mentioned spectrum data SD or a standard substance.

[0056] Here, detector 348 detects the intensity of light emitted from detection target portion 262 at each of a plurality of time points up to the separation time point when electrophoresis unit 20 electrophoreses the main measurement sample (second sample) in detection target portion 262 of capillary 26. Furthermore, detector 348 does not detect the intensity of light emitted from detection target portion 262 at time points after the separation time point when electrophoresis unit 20 electrophoreses the main measurement sample in detection target portion 262. The main measurement sample is a sample different from the test sample.

[0057] 9, the separation time identifying unit 108 identifies time t3 as the separation time. Therefore, when the electrophoresis unit 20 electrophoreses the measurement sample, the detector 348 detects the intensity of light emitted from the detection target portion 262 at each of a plurality of time points up to time t3, but does not detect the intensity of light emitted from the detection target portion 262 at any time point after the separation time point.

[0058] According to the separation time identifying unit 108 described above, when it is only desired to know whether or not a target substance is contained in a sample, the measurement can be terminated at the earliest timing at which the target substance separates from other substances, thereby improving the efficiency of analysis. In other words, the separation time identifying unit 108 makes it easy to search for optimal conditions for analysis. For example, when the capillary electrophoresis apparatus 1 of this embodiment is used for blood testing, it is possible to efficiently analyze whether or not a target substance (such as a marker molecule for a certain disease) is contained in the blood of each of a plurality of subjects.

[0059] [3. Processing performed by capillary electrophoresis device 1] Next, the processes shown in Fig. 10, Fig. 11, Fig. 12, Fig. 13A, and Fig. 13B will be described. The processes shown in Fig. 10, Fig. 11, Fig. 12, Fig. 13A, and Fig. 13B are executed by the control unit of the information processing device 10 operating in accordance with a program stored in the storage unit of the information processing device 10.

[0060] FIG. 10 is a flow diagram showing an example of an analytical method by capillary electrophoresis according to this embodiment. First, the electrophoresis unit 20 electrophoreses the sample in the detection target portion 262 of the capillary 26 (S1000), and the light source 32 irradiates the sample with light (S1002). Next, the detector 348 detects the intensity of light emitted from the detection target portion 262 at each of a plurality of time points (S1004). In S1004, each light receiving portion 3482 of the detector 348 detects the intensity of light for each wavelength component dispersed by the spectroscope 346 by each of the plurality of light receiving portions 3482. Also, in S1004, the detector 348 continues to detect the intensity of light emitted from the detection target portion 262 for a predetermined period. In S1004, the information processing device 10 acquires measurement data MD relating to each of a plurality of time points. Thereafter, the information processing device 10 acquires measurement data MD relating to each of a plurality of time points at time points t i The light intensity distribution data ID is acquired for each of the one or more positions indicated by the light intensity distribution data ID (S1006), and then spectral data SD indicating the spectrum of light detected by the light receiving unit 3482 corresponding to each of the one or more positions indicated by the light intensity distribution data ID is acquired (S1008), after which the process is terminated.

[0061] 11 is a flow diagram showing an example of the process of the association unit 104. i The light intensity distribution data ID and time t i Next, the information processing device 10 acquires the spectrum data SD relating to the time point t i+1 The light intensity distribution data ID and time t i+1 The information processing device 10 acquires the spectrum data SD relating to the time t i+1 At least one of the positions of the light intensity distribution data ID related to the i The information processing device 10 associates the light intensity distribution data ID with one of one or more positions indicated by the light intensity distribution data ID associated with the light intensity distribution data ID (S1104). The information processing device 10 determines whether or not the processes of S1100 to S1104 have been executed for all light intensity distribution data IDs (S1106), and if it determines that the processes have not been executed for all light intensity distribution data IDs (S1106; N), it repeats the processes of S1100 to S1104. If the information processing device 10 determines that the processes have been executed for all light intensity distribution data IDs (S1106; Y), this process ends.

[0062] 12 is a flow diagram showing an example of the process of the mobility calculation unit 106. Note that, in FIG. 12, a case where the mobility μ of a molecule A is calculated is illustrated as an example, similar to the example of FIG. 7. The information processing device 10 calculates the mobility μ of a molecule A at a time t i The information processing device 10 acquires the light intensity distribution data ID relating to (S1200). Next, the information processing device 10 calculates the mobility μ of molecule A (S1202). It is determined whether or not the processes of S1100 to S1104 have been executed for all light intensity distribution data IDs (S1204), and if it is determined that the processes have not been executed for all light intensity distribution data IDs (S1204; N), the processes of S1200 to S1102 are repeated. If the information processing device 10 determines that the processes have been executed for all light intensity distribution data IDs (S1204; Y), this process is terminated.

[0063] 13A and 13B are flow charts showing an example of the process of the separation time point specifying unit 108. Note that, like the example of FIG. 8, FIGS. 13A and 13B illustrate a case where molecule B is isolated and analyzed from a mixture containing molecules A, B, and C. First, the information processing device 10 detects a time point t i Then, the information processing device 10 determines whether or not the position where molecule B exists has become separated from the positions where molecules A and C exist (S1302). When the information processing device 10 determines that the position where molecule B exists has become separated from the positions where molecules A and C exist (S1302; Y), at time t i As the separation time point (S1304), the process proceeds to the process shown in Fig. 13B. When the information processing device 10 determines that the position where molecule B exists is not separated from the positions where molecules A and C exist (S1302; N), the process of S1300 is repeated.

[0064] 13B, the electrophoresis unit 20 electrophoreses the measurement sample in the detection target portion 262 of the capillary 26 (S1306). The processes of S1308, S1314, and S1316 are similar to the processes of S1002, S1006, and S1008 in FIG. 10, and therefore will not be described. After the process of S1308, the detector 348 detects the intensity of light emitted from the detection target portion 262 at each of a plurality of time points until the separation point (S1310). After detection up to the separation point, the detector 348 ends detection of the intensity of light emitted from the detection target portion 262.

[0065] [4. Notes] (1) an electrophoresis unit for electrophoresing a sample in a detection target portion of the capillary; A light source that irradiates the sample with light; a detector having a plurality of light receiving units provided at a plurality of detection positions aligned along the extension direction of the capillary, the detector detecting the intensity of light emitted from the detection target portion at each of a plurality of time points by each of the plurality of light receiving units; A capillary electrophoresis apparatus comprising: (2) The apparatus further includes a spectrometer that separates the light emitted from the detection target portion into a plurality of wavelength components, the light receiving unit provided at each of the plurality of detection positions detects the light intensity for each of the wavelength components; A capillary electrophoresis apparatus according to (1). (3) a light intensity distribution data acquisition unit that acquires light intensity distribution data indicating a distribution of light intensity in the detection target portion of a predetermined wavelength component among the plurality of wavelength components detected by each of the plurality of light receiving units for each of the plurality of time points based on measurement data that is a detection result of the detector at each of the plurality of time points, The light intensity distribution data indicates one or more positions in the detection target portion where one or more detection target substances, which are one or more sample substances contained in the sample or one or more substances derived from at least one of the one or more sample substances, are present. A capillary electrophoresis apparatus according to (1) or (2). (4) a spectrum data acquisition unit that acquires first spectrum data and second spectrum data based on the measurement data related to each of the plurality of time points; an associating unit that associates at least one of the one or more positions of the light intensity distribution data relating to a first time point with any of the one or more positions indicated by the light intensity distribution data relating to a second time point based on the first spectral data and the second spectral data, the first spectral data indicates a spectrum of light detected by the light receiving unit corresponding to each of the one or more positions indicated by the light intensity distribution data relating to the first time point among the plurality of time points, the second spectral data indicates a spectrum of light detected by the light receiving unit corresponding to each of the one or more positions indicated by the light intensity distribution data relating to the second time point among the plurality of time points; A capillary electrophoresis apparatus according to any one of (1) to (3). (5) a mobility calculation unit that calculates at least one mobility of the one or more detection target substances in each of a plurality of sections of the detection target portion based on the light intensity distribution data relating to at least a portion of the plurality of time points, A capillary electrophoresis apparatus according to (3) or (4). (6) a separation time identifying unit that identifies, among the plurality of time points, the earliest time point at which a position of a first substance, which is one of the one or more detection target substances, and a position of a second substance, which is another one of the one or more detection target substances, are observed separated from each other, based on the light intensity distribution data relating to at least a portion of the plurality of time points, when the electrophoresis unit electrophoreses a first sample, which is the sample, in the detection target portion of the capillary; the detector detects an intensity of light emitted from the detection target portion at each of the plurality of time points up to the separation time point when the electrophoresis unit electrophoreses the second sample, which is the sample, in the detection target portion of the capillary. A capillary electrophoresis apparatus according to any one of (3) to (5). [Explanation of symbols]

[0066] 1 capillary electrophoresis apparatus, 10 information processing device, 20 electrophoresis section, 26 capillary, 262 detection target portion, 30 measurement section, 32 light source, 34 spectroscopic detector, 346 spectrometer, 348 detector, 3482 light receiving section, PD light receiving element 100 light intensity distribution data acquisition section, 102 spectrum data acquisition section, 104 association section, 106 mobility calculation section, 108 separation time point identification section, DP detection position, MD measurement data, ID light intensity distribution data, SD spectrum data, SM sample substance, PM generated substance.

Claims

1. an electrophoresis unit for electrophoresing a sample in a detection target portion of the capillary; A light source that irradiates the sample with light; a detector having a plurality of light receiving units provided at a plurality of detection positions aligned along the extension direction of the capillary, the detector detecting the intensity of light emitted from the detection target portion at each of a plurality of time points by each of the plurality of light receiving units; A capillary electrophoresis apparatus comprising:

2. The apparatus further includes a spectrometer that separates the light emitted from the detection target portion into a plurality of wavelength components, the light receiving unit provided at each of the plurality of detection positions detects the light intensity for each of the wavelength components; The capillary electrophoresis apparatus according to claim 1 .

3. a light intensity distribution data acquisition unit that acquires light intensity distribution data indicating a distribution of light intensity in the detection target portion of a predetermined wavelength component among the plurality of wavelength components detected by each of the plurality of light receiving units for each of the plurality of time points based on measurement data that is a detection result of the detector at each of the plurality of time points, The light intensity distribution data indicates one or more positions in the detection target portion where one or more detection target substances, which are one or more sample substances contained in the sample or one or more substances derived from at least one of the one or more sample substances, are present. The capillary electrophoresis apparatus according to claim 2 .

4. a spectrum data acquisition unit that acquires first spectrum data and second spectrum data based on the measurement data related to each of the plurality of time points; an associating unit that associates at least one of the one or more positions of the light intensity distribution data relating to a first time point with any of the one or more positions indicated by the light intensity distribution data relating to a second time point based on the first spectral data and the second spectral data, the first spectral data indicates a spectrum of light detected by the light receiving unit corresponding to each of the one or more positions indicated by the light intensity distribution data relating to the first time point among the plurality of time points, the second spectral data indicates a spectrum of light detected by the light receiving unit corresponding to each of the one or more positions indicated by the light intensity distribution data relating to the second time point among the plurality of time points; The capillary electrophoresis apparatus according to claim 3 .

5. a mobility calculation unit that calculates at least one mobility of the one or more detection target substances in each of a plurality of sections of the detection target portion based on the light intensity distribution data relating to at least a portion of the plurality of time points, 5. The capillary electrophoresis apparatus according to claim 3 or 4.

6. a separation time identifying unit that identifies, among the plurality of time points, the earliest time point at which a position of a first substance, which is one of the one or more detection target substances, and a position of a second substance, which is another one of the one or more detection target substances, are observed separated from each other, based on the light intensity distribution data relating to at least a portion of the plurality of time points, when the electrophoresis unit electrophoreses a first sample, which is the sample, in the detection target portion of the capillary; the detector detects an intensity of light emitted from the detection target portion at each of the plurality of time points up to the separation time point when the electrophoresis unit electrophoreses a second sample, which is the sample, in the detection target portion of the capillary.

5. The capillary electrophoresis apparatus according to claim 3 or 4.

7. Electrophoresing a sample in a detection target portion of the capillary; Irradiating the sample with light by a light source; detecting the intensity of light emitted from the detection target portion at each of a plurality of time points by a detector having a plurality of light receiving units provided at each of a plurality of detection positions aligned along a direction corresponding to the extension direction of the capillary; The present invention relates to a method for analyzing a liquid crystal display using capillary electrophoresis.

8. A means for electrophoresing a sample in a detection target portion of the capillary; A means for irradiating the sample with light by a light source; a detector for detecting the intensity of light emitted from the detection target portion at each of a plurality of time points using a detector having a plurality of light receiving units provided at each of a plurality of detection positions aligned in a direction corresponding to the extension direction of the capillary; A program that makes a computer function as a

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