Electrophoresis data processing device and electrophoresis data processing method

Abstract

In order to improve the accuracy of determining the presence or absence of saturation in a measurement unit of an electrophoresis device, the present invention is provided with: a frequency spectrum generation unit (111) that generates a frequency spectrum of a signal acquired from a measurement unit (20) of an electrophoresis device in which light-receiving elements are virtually coupled; the light receiving element receives light obtained by splitting fluorescent light emitted from a capillary tube of the electrophoresis device; and a saturation determination value setting unit (112) that determines whether or not saturation has occurred in the measurement unit on the basis of the shape of the generated spectrum.

Description

Technical Field

[0001] The present invention relates to techniques for an electrophoresis data processing apparatus and an electrophoresis data processing method. Background Art

[0002] In the analysis of biological samples, a multi-capillary electrophoresis apparatus (hereinafter referred to as an electrophoresis apparatus) is widely used. In the electrophoresis apparatus, an electrolyte solution, or an electrophoresis separation medium such as an electrolyte solution containing a polymer gel or a polymer, is filled in a plurality of capillaries. On this basis, electrophoresis analysis is performed in parallel. The analysis targets in electrophoresis range from low molecules to high molecules such as proteins and nucleic acids.

[0003] In particular, the detection of nucleic acids based on an electrophoresis apparatus is performed through the following process. First, excitation light is irradiated onto a sample to which a fluorescent label is attached to the nucleic acid. Thereafter, the base sequence and length of the nucleic acid are analyzed based on the fluorescence signal emitted by the fluorescent label. The electrophoresis apparatus detects the fluorescence signal by an image sensor such as a CCD (Charge Coupled Device) image sensor or a CMOS (Complementary Metal Oxide Semiconductor) image sensor. And, the electrophoresis apparatus generates a signal intensity for each wavelength based on the detected fluorescence signal, and analyzes the base sequence and length of the nucleic acid.

[0004] In the electrophoresis apparatus, the higher the concentration of the sample for electrophoresis, the higher the generated signal intensity linearly. However, when the concentration of the sample is higher than a certain level, the amount of electric charge generated by the fluorescence signal emitted by the fluorescent label exceeds the saturation charge amount of the image sensor. At this time, the concentration of the sample and the generated signal intensity no longer respond linearly. This is called saturation or exceeding the detection limit.

[0005] On the other hand, nucleic acids are sometimes used for the diagnosis of diseases by calculating the ratio of wild-type nucleic acids to mutant nucleic acids.

[0006] If a saturated sample is determined to be unsaturated and the signal intensity obtained from the sample is used, the mutation rate cannot be correctly detected. That is, it is not desirable to determine a saturated sample as unsaturated. Therefore, it is necessary to determine whether the signal has saturated, add a mark to the saturated signal, and prompt the user to pay attention.

[0007] In an electrophoresis apparatus, saturation is defined by the saturation charge amounts of an image sensor and an analog / digital converter. For example, Patent Document 1 describes a multi-capillary electrophoresis apparatus, "The multi-capillary electrophoresis apparatus includes: a multi-capillary array electrophoresis unit that arranges a plurality of capillary columns, injects a plurality of samples one by one into the capillary columns, and performs electrophoresis simultaneously in all the capillary columns; an optical measurement unit that irradiates light on the capillaries in the multi-capillary array electrophoresis unit, scans the irradiation position in a direction orthogonal to the electrophoresis direction, and measures the intensity of light from the sample in the irradiated portion to obtain a scan waveform; and a data processing unit that uses the light intensity measurement values at predetermined positions of each capillary as data based on the scan waveform obtained by the optical measurement unit and creates time-series data for each capillary. The data processing unit includes: a correction data storage unit that stores correction data for representing the relationship between the number of data points of the saturated portion and the light intensity data when the peak of the scan waveform exceeds the detection range of the detector of the optical measurement unit or the input range of the A / D converter when data is taken into the data processing unit; and a saturation data correction unit that corrects the light intensity measurement value for the peak that is saturated in the scan waveform based on the correction data stored in the correction data storage unit. The data processing unit creates the time-series data based on the light intensity measurement value corrected by the saturation data correction unit for the saturated peak of the scan waveform" (see Claim 1).

[0008] In addition, the determination of whether saturation occurs is made based on the signal intensity. For example, Patent Document 2 describes the following: "Electrons from a CCD are combined with each other before being read into digital numbers from 0 to 65535. However, if there are too many electrons and the signal obtained by converting them into a combined number exceeds the limit of 65535, the measured signal is inaccurate. Such a signal is called'saturation' or 'exceeding the measurement limit.'" (see the mode for carrying out the invention). In addition, Patent Document 2 describes the following as a method for adding a saturation mark: "Determine the interval (bin) of the image that generates a signal with a larger number of electrons than the maximum camera signal, and set an exceeding the measurement limit mark for the determined interval" (see Claim 1). Thus, Patent Document 2 discloses adding a saturation mark to the interval when the signal intensity exceeds "65535" (unit: ADU (Analog to Digital Unit)).

[0009] Prior Art Documents

[0010] Patent Documents

[0011] Patent Document 1: Japanese Patent No. 4175735 Specification

[0012] Patent Document 2: Specification of US Patent Application Publication No. 2020 / 0074624 Summary of the Invention

[0013] Problems to be Solved by the Invention

[0014] In Patent Document 1, there is a description of saturation when "exceeding the detection range of the detector of the optical measurement unit or the input range of the A / D converter when taking in data in the data processing unit", but there is no description of how to detect saturation.

[0015] In addition, in Patent Document 2, saturation is determined when the signal intensity exceeds "65535" (ADU), and a mark is added to the saturated section.

[0016] Here, it is known that binning is performed by analogously combining a plurality of light-receiving elements constituting an image sensor and processing them as if they were a single light-receiving element. When the number of combined light-receiving surfaces is large, saturation is defined by the saturation charge amount of the analog / digital converter, rather than the saturation charge amount of the image sensor. On the other hand, when the number of combined light-receiving surfaces is small, saturation is defined by the saturation charge amount of the image sensor, rather than the saturation charge amount of the analog / digital converter.

[0017] In addition, there are differences in the saturation charge amounts of the image sensor and the analog / digital converter between devices. Therefore, the fluorescence signal intensity at saturation varies depending on the device.

[0018] Therefore, in a method of setting a certain threshold value and determining saturation when it is above the threshold value, saturation may sometimes not be detected. If a saturated signal is determined to be unsaturated and its signal intensity is used, misdiagnosis or the like may occur as described above.

[0019] In view of such a background, the present invention has been completed. The object of the present invention is to improve the determination accuracy of the presence or absence of saturation in the measurement unit of an electrophoresis apparatus.

[0020] Means for Solving the Problems

[0021] To solve the above problems, the present invention is characterized by having: a spectrum generation unit that generates a spectrum of a signal obtained from a measurement unit of an electrophoresis apparatus in which light-receiving elements are virtually combined by binning, the light-receiving elements receiving light obtained by splitting fluorescence emitted from a capillary tube included in the electrophoresis apparatus; and a saturation determination processing unit that determines whether saturation has occurred in the measurement unit based on the shape of the generated spectrum.

[0022] Other means for solving the problems are appropriately described in the embodiments.

[0023] Advantages of the Invention

[0024] According to the present invention, it is possible to improve the determination accuracy of saturation presence or absence in the measurement unit of the electrophoresis apparatus. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 It is a diagram showing an outline of a structural example of the electrophoresis apparatus according to the 1-1st Embodiment.

[0026] Figure 2 It is a diagram showing an outline of the structure of the fluorescence detection apparatus according to the 1-1st Embodiment.

[0027] Figure 3 It is a diagram showing an outline of the structure of the CCD image sensor according to the 1-1st Embodiment.

[0028] Figure 4 It is a diagram showing the structure of the processing unit according to the 1-1st Embodiment.

[0029] Figure 5 It is a diagram (Part 1) for explaining the operation of converting the spectro-dispersed fluorescence signal into a digital signal.

[0030] Figure 6 It is a diagram (Part 2) for explaining the operation of converting the spectro-dispersed fluorescence signal into a digital signal.

[0031] Figure 7 It is a diagram (Part 3) for explaining the operation of converting the spectro-dispersed fluorescence signal into a digital signal.

[0032] Figure 8 It is a diagram showing the timing at which the control unit applies a pulse.

[0033] Figure 9 It is a diagram showing a structural example of a generalized interval.

[0034] Figure 10 It is a diagram showing an outline of the measurement unit and the processing unit according to the 1-1st Embodiment.

[0035] Figure 11 It is a flowchart showing the process of the saturation determination value setting process according to the 1-1st Embodiment.

[0036] Figure 12 It is a flowchart showing the process of the saturation determination process of the saturation determination unit according to the 1-1st Embodiment.

[0037] Figure 13 It is a diagram showing an example of a spectrum where saturation does not occur.

[0038] Figure 14 It is a diagram showing an example of a spectrum where saturation occurs in the summing gate.

[0039] Figure 15 It is a diagram showing an example of a spectrum in which a charge storage element has become saturated.

[0040] Figure 16 It is a diagram showing an example of an electrophoresis image.

[0041] Figure 17 It is a diagram showing an example of a spectrum in the first - 1 embodiment.

[0042] Figure 18A It is a schematic diagram (part 1) showing the case of saturation when the interval is composed of nine light - receiving elements.

[0043] Figure 18B It is a schematic diagram (part 2) showing the case of saturation when the interval is composed of nine light - receiving elements.

[0044] Figure 18C It is a schematic diagram (part 3) showing the case of saturation when the interval is composed of nine light - receiving elements.

[0045] Figure 19A It is a schematic diagram (part 1) showing the case of saturation when the interval is composed of three light - receiving elements.

[0046] Figure 19B It is a schematic diagram (part 2) showing the case of saturation when the interval is composed of three light - receiving elements.

[0047] Figure 19C It is a schematic diagram (part 3) showing the case of saturation when the interval is composed of three light - receiving elements.

[0048] Figure 20 It is a diagram showing an outline of the structure of the electrophoresis apparatus in the first - 2 embodiment.

[0049] Figure 21 It is a diagram showing a detailed structural example of the processing unit in the first - 2 embodiment.

[0050] Figure 22 It is a flowchart showing the process of the saturation determination process of the saturation determination unit in the first - 2 embodiment.

[0051] Figure 23 It is a diagram showing the structure of the processing unit in the first - 3 embodiment.

[0052] Figure 24 It is a flowchart showing the process of the saturation determination value setting process of the saturation determination value setting unit in the first - 3 embodiment.

[0053] Figure 25It is a flowchart showing the process of the saturation determination value setting process in the 2-1st embodiment.

[0054] Figure 26 It is a graph (part 1) showing the spectral sum and the absolute value of the second derivative related to the spectrum.

[0055] Figure 27 It is a graph (part 2) showing the spectral sum and the absolute value of the second derivative related to the spectrum.

[0056] Figure 28 It is a flowchart showing the process of the saturation determination process in the 2-2nd embodiment.

[0057] Figure 29 It is a flowchart showing the process of the saturation determination value setting process in the 2-3rd embodiment.

[0058] Figure 30 It is a diagram showing an overview of the structure of the electrophoresis apparatus in the 3-1st embodiment.

[0059] Figure 31 It is a diagram showing the details of the structure of the processing unit in the 3-1st embodiment.

[0060] Figure 32 It is a flowchart showing the process of the saturation determination value setting process in the 3-1st embodiment.

[0061] Figure 33 It is a diagram showing the details of the structure of the processing unit in the 3-2nd embodiment.

[0062] Figure 34 It is a flowchart showing the process of determining the saturation of the saturation determination unit in the 3-2nd embodiment.

[0063] Figure 35 It is a diagram showing the structure of the processing unit in the 3-3rd embodiment.

[0064] Figure 36 It is a flowchart showing the process of the saturation determination value setting process in the 3-3rd embodiment.

[0065] Figure 37 It is a diagram showing the hardware structure diagram of the processing unit. Detailed Embodiments

[0066] Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. In addition, in all the drawings used to describe the embodiments, the same reference numerals are assigned to the same structures in principle, and repeated descriptions thereof are omitted.

[0067] 《First Embodiment》

[0068] <First - 1 Embodiment>

[0069] [System Structure]

[0070] Figure 1 It is a diagram showing an outline of the structural example of the electrophoresis apparatus 1 of the First - 1 Embodiment.

[0071] As Figure 1 shown, the electrophoresis apparatus 1 has a processing unit 10 and a measurement unit 20 which are electrophoresis data processing apparatuses.

[0072] (Measurement Unit 20)

[0073] The measurement unit 20 has: a pump unit 21, a high - voltage power supply 22, a thermostat 23, a fluorescence detection device 200, and a capillary array 240. In addition, the measurement unit 20 has a sample tray 250 and a transporter 260.

[0074] The sample tray 250 houses a plurality of sample containers 251. Each sample container 251 is a container in which a sample of DNA (Deoxyribonucleic Acid) to be measured, which is attached with a fluorescent label, is placed. And different samples are placed in each sample container 251.

[0075] The transporter 260 transports the sample tray 250 so that each sample container 251 is located at the front end position of the capillary 241.

[0076] The capillary array 240 is composed of a plurality of capillaries 241. Each capillary 241 is hollow. In addition, each capillary 241 is inserted into the sample container 251.

[0077] The thermostat 23 maintains the inside of the capillary array 240 at a constant temperature.

[0078] The pump unit 21 injects an electrophoresis medium M (for example, a polymer) into the inside of each capillary 241. Thus, the inside of each capillary 241 is filled with the electrophoresis medium M.

[0079] The high - voltage power supply 22 applies a high voltage to both ends of each capillary 241 filled with the electrophoresis medium M.

[0080] The fluorescence detection position 24 is set on the path where the sample is electrophoresed. At the fluorescence detection position 24, excitation light R1 (refer to Figure 2 ) is irradiated to the sample.

[0081] The sample is electrophoresed through the capillary 241 by the high - voltage power supply 22 and moves inside the capillary 241. The moving direction of the sample is indicated by an arrow. The sample moving inside the capillary 241 is irradiated with excitation light R1 at the fluorescence detection position 24 (refer to Figure 2) emits fluorescence. After that, the sample is discharged into the discharge container 25. In addition, the fluorescence detection device 200 detects a fluorescence signal R2 based on the fluorescence emitted from the sample at the fluorescence detection position 24 (see Figure 2 ). The detailed structure of the fluorescence detection device 200 will be described later. The measurement unit 20 has such a structure that it can simultaneously measure samples electrophoresed inside a plurality of capillaries 241.

[0082] In the present embodiment, as the sample passing through the inside of the capillary 241, a DNA fragment labeled with fluorescence is assumed, but samples other than DNA fragments can also be used.

[0083] (Processing unit 10)

[0084] The processing unit 10 includes a fluorescence correction unit 101, a color conversion unit 103, a saturation determination value setting unit 112, a saturation determination unit 113, etc. The structure of each unit in the processing unit 10 and the processing performed by each unit will be described later in the item of operation.

[0085] (Fluorescence detection device 200)

[0086] Figure 2 is a diagram showing an outline of the structure of the fluorescence detection device 200 in the 1-1st embodiment.

[0087] As Figure 2 shown, the fluorescence detection device 200 includes: an excitation light source 201, a shutter 202, and an excitation light lens 203. In addition, the fluorescence detection device 200 includes: an optical filter 204, a fluorescence lens 205, a diffraction grating 206, and a CCD image sensor 210. And the fluorescence detection device 200 includes a control unit 220 and a conversion unit 230.

[0088] The excitation light source 201 continuously emits excitation light R1. The excitation light source 201 is arranged to irradiate the excitation light R1 emitted to all the capillaries 241 in the capillary array 240 passing through the fluorescence detection position 24.

[0089] The shutter 202 opens and closes repeatedly at a predetermined interval. That is, when the shutter 202 is open, the excitation light R1 irradiated from the excitation light source 201 irradiates the capillary 241. And when the shutter 202 is closed, the irradiation of the excitation light R1 to the capillary 241 is blocked.

[0090] The excitation light lens 203 condenses the excitation light R1 that has passed through the shutter 202. The excitation light R1 condensed by the excitation light lens 203 is irradiated toward the fluorescence detection position 24.

[0091] As described above, the samples inside the respective capillaries 241 use DNA fragments to which fluorescent labels are attached as described above. The fluorescent labels attached to the DNA fragments electrophoresed inside the respective capillaries 241 are excited by irradiating excitation light R1 and emit fluorescence signals R2.

[0092] The optical filter 204 (e.g., color filter) cuts off light other than the fluorescence signal R2 emitted from the fluorescent label. As the optical filter 204, a color filter is used, for example.

[0093] The fluorescence lens 205 condenses the fluorescence signal R2 that has passed through the optical filter 204.

[0094] The diffraction grating 206 disperses the fluorescence signal R2 condensed by the fluorescence lens 205 by wavelength.

[0095] The CCD image sensor 210 receives the fluorescence signal R2 dispersed by the diffraction grating 206 and outputs charges corresponding to the intensity of the fluorescence signal R2.

[0096] The control unit 220 instructs the CCD image sensor 210 to output charges based on the fluorescence signal R2.

[0097] The conversion unit 230 includes a charge conversion unit 231 and a digital conversion unit 232 as an ADC (Analog Digital Converter).

[0098] The charge conversion unit 231 converts the charges output from the CCD image sensor 210 into a voltage and outputs the converted voltage as an analog signal.

[0099] The digital converter 232 converts the analog signal output from the charge converter 231 into a digital signal. Then, the digital conversion unit 232 outputs the converted digital signal to the processing unit 10.

[0100] Next, with reference to Figure 1 and Figure 2 , the measurement of the sample will be described.

[0101] First, the sample is accommodated in the sample container 251. Then, a high voltage is applied to both ends of each capillary 241 by the high-voltage power supply 22, whereby the sample moves from the sample container 251 into the capillary 241. Thus, the sample moves inside the capillary 241 (electrophoresis) via the fluorescence detection position 24 toward the discharge container 25. When electrophoresis is performed on the sample, the moving speed varies according to the base length of the DNA fragment that is the sample. Therefore, the DNA fragments with shorter base lengths reach the fluorescence detection position 24 in sequence. The excitation light R1 emitted from the excitation light source 201, passing through the shutter 202 and condensed by the excitation light lens 203, irradiates the sample that has reached the fluorescence detection position 24. The fluorescence label attached to the DNA fragment is excited by the irradiation of the excitation light R1 and emits a fluorescence signal R2. The fluorescence signal R2 passes through the optical filter 204, is condensed by the fluorescence lens 205, and is spectrally separated by wavelength by the diffraction grating 206.

[0102] (CCD image sensor 210)

[0103] Figure 3 is a diagram showing an outline of the structure of the CCD image sensor 210 in the first-1 embodiment. Refer to appropriately Figure 2 .

[0104] As Figure 3 shown, the CCD image sensor 210 has a light-receiving portion 211 and an integrating portion 212.

[0105] The light-receiving portion 211 has a plurality of light-receiving elements 211A arranged in a lattice pattern. Each light-receiving element 211A is a surface that receives the fluorescence signal R2 spectrally separated by wavelength by the diffraction grating 206. That is, the light-receiving element 211A receives the light obtained by spectral separation of the fluorescence emitted from the capillary 241 of the electrophoresis apparatus 1. When the light-receiving element 211A receives the fluorescence signal R2, it outputs a signal charge corresponding to the intensity of the fluorescence signal R2.

[0106] The integrating portion 212 has: a charge storage portion 213, a horizontal register portion 214, and a summing gate 215.

[0107] The charge storage portion 213 has charge storage elements 213A corresponding one-to-one to the light-receiving elements 211A. Each charge storage element 213A stores the charge transferred from the corresponding light-receiving element 211A. In addition, the charge storage portion 213 is connected to the control portion 220 via the pulse line L1. The charge storage elements 213A constituting the charge storage portion 213 output charges respectively according to the instructions of the control portion 220 passed through the pulse line L1. Details of the output of the charges of the charge storage elements 213A will be described later.

[0108] The horizontal register section 214 has a plurality of horizontal registers 214A. The horizontal registers 214A accumulate the charges stored in the charge storage elements 213A in the vertical direction. In addition, in the present embodiment, the direction from the charge storage section 213 toward the horizontal register 214A is referred to as the vertical direction, and the direction from the horizontal register section 214 toward the summing gate 215 is referred to as the horizontal direction. The horizontal register section 214 is connected to the control section 220 via the pulse line L2. Each of the horizontal registers 214A constituting the horizontal register section 214 outputs charges according to an instruction from the control section 220 via the pulse line L2. Details of the output of charges from the horizontal register 214A will be described later.

[0109] The summing gate 215 accumulates the charges accumulated by the horizontal register section 214 in the horizontal direction. The summing gate 215 is connected to the control section 220 via the pulse line L3. The summing gate 215 outputs the accumulated charges according to an instruction from the control section 220 via the pulse line L3.

[0110] In addition, as the CCD image sensor 210, any one of a frame transfer type, a full frame transfer type, an interline transfer type, and a frame interline transfer type can be applied. In the case of applying the frame transfer type, the interline transfer type, or the frame interline transfer type, it is not necessary to provide the shutter 202 (refer to Figure 2 ). Further, in the case of applying the full frame transfer type, by increasing the number and area of the light receiving elements 211A, it is possible to detect minute signals.

[0111] Alternatively, instead of the CCD image sensor 210, a CMOS image sensor (Complementary Metal Oxide Semiconductor) can be applied to the detection of the fluorescence signal R2 (refer to Figure 2 ). In the case of applying the CMOS image sensor, digital signals can be directly obtained from the respective light receiving elements 211A.

[0112] [Processing section 10]

[0113] Figure 4 is a diagram showing the structure of the processing section 10 in the 1-1st embodiment. Refer to appropriately Figure 1 .

[0114] The processing section 10 includes: a fluorescence correction section 101, a pseudo inverse matrix generation section 102, a color conversion section 103, a spectrum generation section 111, a saturation determination value setting section 112, and a saturation determination section 113.

[0115] In the electrophoresis apparatus 1, in order to obtain the signal intensity of a sample to be analyzed (hereinafter referred to as the analyzed sample D10), a matrix standard D20 is used separately from the analyzed sample D10. The matrix standard D20 is a sample for fluorescence correction. In addition, in the present embodiment, the analyzed sample D10 is a DNA fragment to which a fluorescent label is attached.

[0116] The processing performed by the fluorescence correction unit 101, the pseudo-inverse matrix generation unit 102, the color conversion unit 103, the spectrum generation unit 111, the saturation determination value setting unit 112, and the saturation determination unit 113 in the processing unit 10 will be described later. In addition, the analyzed sample signal D11, the matrix standard signal D21, the fluorescence spectrum data D22, the pseudo-inverse matrix D23, the spectrum SP, and the saturation determination value D30 will also be described later.

[0117] [Example where saturation occurred in the summing gate 215]

[0118] Figures 5 - 7 is a diagram for explaining the operation of converting the spectro-dispersed fluorescence signal R2 (refer to Figure 2 ) into a digital signal, showing an example where saturation occurred in the summing gate 215. Refer to Figure 2 as appropriate. In addition, in Figures 5 - 7 (and in Figure 3 ), the dashed lines shown for the light receiving element 211A and the charge storage element 213A represent the interval B. The interval B will be described later.

[0119] First, as shown in Figure 2 , the fluorescence signal R2 spectro-dispersed by wavelength by the diffraction grating 206 (refer to Figure 2 ) is received by the light receiving element 211A of the measurement unit 20. Then, as shown in Figure 5 , charges are stored in the charge storage element 213A corresponding to the light receiving element 211A. In the example shown in the present embodiment, it is assumed that "120 ke - " of charges are generated in each light receiving element 211A. As described above, each charge storage element 213A corresponds one-to-one with the light receiving element 211A, and thus, "120 ke - " of charges are stored in each charge storage element 213A. In addition, in the present embodiment, the saturation charge amount of each charge storage element 213A is "320 ke - ", the saturation charge amount of the horizontal register 214A is "1000 ke - ", and the saturation charge amount of the summing gate 215 is "1000 ke -”. Additionally, in the present embodiment, it is assumed that the digital conversion unit 232 converts the analog signal value when the summing gate 215 is saturated into a digital signal value of "65535" (ADU) for explanation. These operations are performed synchronously with the timing when the shutter 202 is opened. The period from the state where the shutter 202 is closed to the state where the shutter 202 becomes open and then the shutter 202 is closed again is called a frame. Additionally, during the period when the charge is transferred from the light-receiving element 211A to the processing unit 10, the shutter 202 is closed.

[0120] Next, the control unit 220 applies a pulse to the pulse line L1 to transfer the charges accumulated in each charge accumulation element 213A in the vertical direction. When the pulse is applied to the pulse line L1, the charges accumulated in each charge accumulation element 213A are transferred one by one in the vertical direction to the light-receiving element 211A.

[0121] Additionally, the charge accumulated in the last charge accumulation element 213A in the vertical direction is transferred to the horizontal register 214A.

[0122] Then, the control unit 220 applies a pulse to the pulse line L1 again to transfer the charges accumulated in each charge accumulation element 213A in the vertical direction. When the pulse is applied to the pulse line L1, the charges accumulated in the charge accumulation element 213A are transferred successively in the vertical direction.

[0123] Additionally, the charge accumulated in the last charge accumulation element 213A in the vertical direction is transferred to the horizontal register 214A. Thus, the charge transferred last time and the charge transferred this time are accumulated in each horizontal register 214A.

[0124] Then, the control unit 220 also applies a pulse to the pulse line L1 to transfer the charges accumulated in each charge accumulation element 213A in the vertical direction. When the pulse is applied to the pulse line L1, the charges accumulated in each charge accumulation element 213A are transferred successively in the vertical direction to the charge accumulation element 213A.

[0125] Additionally, the charge accumulated in the last charge accumulation element 213A in the vertical direction is transferred to the horizontal register 214A. Thus, the charge transferred the time before last, the charge transferred last time, and the charge transferred this time are accumulated in each horizontal register 214A. That is, every time a pulse is applied to the pulse line L1, the charges accumulated in the charge accumulation element 213A are transferred successively to the horizontal register 214A.

[0126] In the example shown in the present embodiment, by applying a total of 3 pulses to the pulse line L1, charges are accumulated in the horizontal register 214A as Figure 6 shown. That is, 120ke is accumulated in each horizontal register 214A. -×3 = "360ke - " of charge.

[0127] Next, the control unit 220 applies a pulse to the pulse line L2 to transfer the charge accumulated in the horizontal register 214A in the horizontal direction. When the pulse is applied to the pulse line L2, the charge accumulated in each horizontal register 214A is sequentially transferred in the horizontal direction.

[0128] In addition, the charge accumulated in the last horizontal register 214A in the horizontal direction is transferred to the summing gate 215.

[0129] Then, the control unit 220 applies a pulse to the pulse line L2 again to transfer the charge accumulated in each horizontal register 214A in the horizontal direction. When the pulse is applied to the pulse line L2, the charge accumulated in each horizontal register 214A is sequentially transferred in the horizontal direction.

[0130] In addition, the charge transferred to the last horizontal register 214A in the horizontal direction is transferred to the summing gate 215. Therefore, the charge transferred last time and the charge transferred this time are accumulated in the summing gate 215.

[0131] The control unit 220 also applies a pulse to the pulse line L2 to transfer the charge accumulated in each horizontal register 214A in the horizontal direction. When the pulse is applied to the pulse line L2, the charge accumulated in each horizontal register 214A is sequentially transferred in the horizontal direction.

[0132] Then, the charge accumulated in the last horizontal register 214A in the horizontal direction is transferred to the summing gate 215. As a result, the charge transferred the time before last, the charge transferred last time, and the charge transferred this time are accumulated in the summing gate 215. As a result, 360ke - ×3 = "1080ke - " of charge is input to the summing gate 215.

[0133] However, as described above, the saturation charge amount of the summing gate 215 is "1000ke - ", so the charge amount of "1080ke - " transferred to the summing gate 215 exceeds the saturation charge amount of the summing gate 215. Therefore, the charge output from the summing gate 215 is as Figure 7 shown as "1000ke - ". After that, the control unit 220 applies a pulse to the summing gate 215 via the pulse line L3, whereby the charge is output from the summing gate 215 to the conversion unit 230 (refer to Figure 3 ).

[0134] In addition, when the charges accumulated in all the charge accumulation elements 213A are transferred to the summing gate 215, the shutter 202 can be opened.

[0135] (Combination)

[0136] Figure 8 is a diagram showing the timing at which the control unit 220 applies pulses.

[0137] In Figure 8 , the timings of the pulses applied to the charge accumulation unit 213, the timings of the pulses applied to the horizontal register unit 214, and the timings of the pulses applied to the summing gate 215 are shown in order from the upper part of the paper surface.

[0138] The charges corresponding to the plurality of light receiving elements 211A are accumulated by the summing gate 215 through the operation described with reference to Figures 5 - 7 . Thus, they can be processed analogously as one light receiving element 211A. In this way, the process of processing a plurality of light receiving elements 211A analogously as one light receiving element 211A is called combination, and the light receiving elements 211A that are analogously combined are called interval B (refer to Figure 3 ).

[0139] In Figures 5 - 8 shown in the example, a total of nine light receiving elements 211A, three in the vertical direction and three in the horizontal direction, are combined into one interval B. Charges are accumulated in the horizontal register 214A and the summing gate 215 for the light receiving elements 211A corresponding to interval B. That is, as in the example shown in Figure 8 , after applying pulses to the charge accumulation unit 213 three times continuously, pulses are applied to the horizontal register unit 214 three times continuously. After that, a pulse is applied to the summing gate 215 once. Thus, a total of nine light receiving elements 211A, three in the vertical direction and three in the horizontal direction, are combined. The interval B generated by this combination is the interval B shown in Figure 3 . In addition, the combined area is not limited to the example shown in Figures 5 - 8 . By changing (making variable) the combined area, the sensitivity of the CCD image sensor 210 can be changed. That is, the size of interval B is variable.

[0140] And, in Figure 8 shown in the example, three pulses for the charge accumulation unit 213, three pulses for the horizontal register 214A, and one pulse for the summing gate 215 are regarded as one group (period T), and such groups are performed multiple times. Then, the groups are repeated until all the charges accumulated in the charge accumulation unit 213 are transferred to the horizontal register 214A.

[0141] Figure 9It is a diagram showing a structural example of a generalized interval B.

[0142] Generally, as Figure 9 shown, it can be considered that an interval B is composed of m light-receiving elements 211A (=charge storage elements 213A) in the vertical direction and n light-receiving elements 211A (=charge storage elements 213A) in the horizontal direction. That is, in Figure 3 、 Figures 5 - 8 the example shown, the interval B is composed of m = 3 and n = 3. And Figure 9 each of the intervals B1 to BN shown does not overlap with each other. By changing the timing of the pulse applied by the control unit 220, the size of the interval B can be changed.

[0143] In this way, in the measurement unit 20 of the present embodiment, a merging in which the light-receiving elements 211A are virtually combined is performed.

[0144] [Outline of the structure]

[0145] Figure 10 It is a diagram showing an outline of the measurement unit 20 and the processing unit 10 in the 1-1st embodiment.

[0146] The control unit 220 issues an instruction to the integration unit 212 to accumulate the charges received by the light-receiving unit 211. Next, the control unit 220 issues an instruction to the conversion unit 230 to convert the charges accumulated by the integration unit 212 into digital signals. By repeatedly performing such instructions for accumulation and conversion, an interval B is generated (refer to Figure 9 ). The digital signals corresponding to the generated intervals B are output to the frequency spectrum generation unit 111 of the processing unit 10. In addition, the frequency spectrum generation unit 111 outputs the frequency spectrum SP of the input digital signal (refer to Figure 4 ) to the saturation determination value setting unit 112. And the saturation determination value setting unit 112 outputs the saturation determination value D30 set based on the frequency spectrum SP (refer to Figure 4 ) to the saturation determination unit 113. The saturation determination unit 113 determines the presence or absence of saturation in the digital signal based on the saturation determination value D30.

[0147] Referring again to Figure 3 .

[0148] The charges accumulated in the summing gate 215 are converted into a voltage corresponding to the number of charges transmitted from the summing gate 215 in the charge conversion unit 231. As a result, the charge conversion unit 231 outputs the converted voltage as an analog signal to the digital conversion unit 232. That is, in Figure 8 the group shown, the charge conversion unit 231 that finally transmits charges from the summing gate 215 outputs a voltage corresponding to the transmitted charge amount as an analog signal.

[0149] The analog signal output from the charge conversion unit 231 is converted into a digital signal by the digital conversion unit 232. The converted digital signal is output to the processing unit 10. In addition, in the present embodiment, the digital signal is appropriately referred to as a "signal", and the digital signal intensity, which is the intensity of the digital signal, is appropriately referred to as the "signal intensity".

[0150] Refer again to Figure 4 。

[0151] The measurement unit 20 outputs an analyte sample signal D11, which is a digital signal (signal) of the analyte sample D10, from the analyte sample D10 by the method shown in Figures 5 - 8 . The output analyte sample signal D11 is the signal intensity related to each interval B in all frames. The output analyte sample signal D11 is input to the color conversion unit 103, the spectrum generation unit 111, and the saturation determination unit 113 of the processing unit 10. Separately from the analyte sample D10, the measurement unit 20 also measures the matrix standard D20. Then, the measurement unit 20 outputs a matrix standard signal D21, which is a digital signal of the matrix standard D20, by the method shown in Figures 5 - 8 . The output matrix standard signal D21 is the signal intensity related to each interval B in all frames. The output matrix standard signal D21 is input to the fluorescence correction unit 101 of the processing unit 10. In addition, the measurements of the analyte sample D10 and the matrix standard D20 are performed separately.

[0152] The fluorescence correction unit 101 normalizes the matrix standard signal D21 output from the measurement unit 20 frame by frame so that the maximum signal intensity is "1" and outputs it to the pseudo-inverse matrix generation unit 102. The normalized digital signal is called fluorescence spectrum data D22.

[0153] Next, when the pseudo-inverse matrix generation unit 102 obtains the fluorescence spectrum data D22 output from the fluorescence correction unit 101, it generates a pseudo-inverse matrix D23 of the fluorescence spectrum data D22. The generated pseudo-inverse matrix D23 is output to the color conversion unit 103.

[0154] Then, the color conversion unit 103 obtains the analyte sample signal D11 from the measurement unit 20 and obtains the pseudo-inverse matrix D23 from the pseudo-inverse matrix generation unit 102. Then, the color conversion unit 103 multiplies the obtained analyte sample signal D11 by the obtained pseudo-inverse matrix D23. Thereby, fluorescence signal data D24 is generated. The color conversion unit 103 outputs the generated fluorescence signal data D24 to the saturation determination unit 113.

[0155] On the other hand, the spectrum generation unit 111 acquires the analysis target sample signal D11 output from the measurement unit 20. Then, the spectrum generation unit 111 generates the spectrum SP of the analysis target sample signal D11.

[0156] The saturation determination value setting unit 112, which is the saturation determination processing unit, sets the saturation determination value D30 based on the shape of the spectrum SP generated by the spectrum generation unit 111. The method for setting the saturation determination value D30 will be described later. Then, the saturation determination value setting unit 112 outputs the set saturation determination value D30 to the saturation determination unit 113. And the saturation determination unit 113, which is the saturation determination processing unit, gives a mark indicating whether saturation has occurred in the analysis target sample signal D11 based on the saturation determination value D30.

[0157] (Saturation determination value setting process)

[0158] Next, with reference to Figure 11 and Figure 12 , the processing procedure of the electrophoresis data processing method in the first-1 embodiment will be described.

[0159] Figure 11 is a flowchart showing the process of the (saturation determination value setting process) in the first-1 embodiment. Appropriate reference is made to Figure 4 .

[0160] First, the spectrum generation unit 111 acquires the analysis target sample signal D11 from the measurement unit 20 (S101). In step S101, the spectrum generation unit 111 acquires the analysis target sample signal D11 related to all frames. In addition, in subsequent processing, the same applies to processing similar to step S101. Step S101 corresponds to the signal acquisition step.

[0161] Next, the spectrum generation unit 111 depicts (generates) the spectrum SP of the analysis target sample signal D11 frame by frame (S102). The spectrum generation unit 111 depicts a curve graph with the horizontal axis being the number of the interval B in the analysis target sample signal D11 and the vertical axis being the signal intensity of the interval B. In this way, the curve graph with the horizontal axis being the number of the interval B and the vertical axis being the signal intensity of the interval B is called the spectrum SP. The spectrum SP of the analysis target sample signal D11 is a spectrum SP generated based on the signal intensity obtained as a result of measuring the sample to be analyzed. Step S102 corresponds to the spectrum generation step.

[0162] Next, the saturation determination value setting unit 112 selects one of the frames. Then, for the selected frame, the saturation determination value setting unit 112 determines whether the maximum signal intensity of the spectrum SP depicted in step S102 is the first threshold TH1 (refer to Figure 13)Above (S103). The first threshold TH1 is preset by the user. Moreover, the first threshold TH1 is set to be sufficiently smaller than the signal intensity at saturation and sufficiently larger than the signal intensity when the analysis target sample D10 is not included in the electrophoresis medium M (refer to Figure 1 ). That is, the signal intensity that is known not to reliably saturate is preset as the first threshold TH1. In the present embodiment, the signal intensity "20000" (ADU) is set as the first threshold TH1.

[0163] When the maximum signal intensity of the spectrum SP is equal to or greater than the first threshold TH1 (S103 → Yes), the saturation determination value setting unit 112 determines whether the shape of the spectrum SP significantly deviates from the shape of the Gaussian distribution, which is a predetermined shape (S104). Specifically, in step S104, the saturation determination value setting unit 112 calculates the sum of the squares of the differences between the spectrum SP and the Gaussian distribution. Then, when the sum of the squares of the differences is equal to or greater than a predetermined threshold (a threshold different from the first threshold TH1), the saturation determination value setting unit 112 determines that the shape of the spectrum SP significantly deviates from the shape of the Gaussian distribution. The case where the shape of the spectrum SP significantly deviates from the shape of the Gaussian distribution will be described later. Step S104 corresponds to the saturation determination step.

[0164] When the shape of the spectrum SP significantly deviates from the shape of the Gaussian distribution (S104 → Yes), the saturation determination value setting unit 112 determines that saturation has occurred in the measurement unit 20 and executes the process of step S105. In step S105, the saturation determination value setting unit 112 records the lowest signal intensity in the portion where the signal intensity in the spectrum SP is substantially constant.

[0165] Next, the saturation determination value setting unit 112 sets the value of the signal intensity recorded in step S105 as the saturation determination value D30 (S106) and outputs it to the saturation determination unit 113 (S107).

[0166] On the other hand, in step S103, when the maximum signal intensity of the spectrum SP is less than the first threshold TH1 (S103 → No), the processing unit 10 proceeds to the next frame (S108). Then, the processing unit 10 performs the processing after step S103 for the next frame.

[0167] In addition, in step S104, when the shape of the spectrum SP does not deviate significantly from the shape of the Gaussian distribution (S104 → No), the saturation determination value setting unit 112 performs the process of step S109. In step S109, the saturation determination value setting unit 112 determines whether the frame to be processed is the final frame. When the frame to be processed is the final frame (S109 → Yes), the saturation determination value setting unit 112 records "65535" (ADU) as the signal intensity (S110). A value such as "65535" (ADU) is, as described above, the signal intensity relative to the saturation charge amount of the summation gate 215. That is, in the example shown in Figure 7 the saturation charge amount of the summation gate 215 is "1000ke - ", and the signal intensity corresponding to "1000ke - " is "65535" (ADU). In step S110, it is only necessary to record the signal intensity corresponding to the saturation charge amount of the summation gate 215, and it is not limited to a value such as "65535" (ADU).

[0168] Then, the saturation determination value setting unit 112 sets the value "65535" (ADU) recorded in step S105 as the saturation determination value D30 (S106). That is, in all frames, when the spectrum SP does not deviate significantly from the shape of the Gaussian distribution, the saturation determination value setting unit 112 sets the signal intensity based on the saturation charge amount of the summation gate 215 as the saturation determination value D30.

[0169] In addition, in step S109, when the frame to be processed is not the final frame (S109 → No), the processing unit 10 moves to the next frame (S111). Then, the processing unit 10 performs the processes after step S103.

[0170] (Saturation determination process)

[0171] Referring again to Figure 4 . As described above, the saturation determination unit 113 obtains the analysis target sample signal D11 from the measurement unit 20. In addition, the saturation determination unit 113 obtains the fluorescence signal data D24 from the color conversion unit 103. And the saturation determination unit 113 obtains the saturation determination value D30 from the saturation determination value setting unit 112. Then, the saturation determination unit 113 determines whether saturation has occurred in the frame to be processed based on the obtained analysis target sample signal D11, fluorescence signal data D24, and saturation determination value D30. Hereinafter, the process performed by the saturation determination unit 113 will be described in detail.

[0172] Figure 12 is a flowchart showing the process of the saturation determination process of the saturation determination unit 113 in the first-1 embodiment. Appropriate reference is made to Figure 4 .

[0173] In Figure 12 the analysis object sample signal D11 used in is the analysis object sample signal D11 used in the processing of Figure 11 .

[0174] First, the saturation determination unit 113 acquires the analysis object sample signal D11 from the measurement unit 20 (S201).

[0175] Next, the saturation determination unit 113 acquires the fluorescence signal data D24 from the color conversion unit 103 (S202).

[0176] Subsequently, the saturation determination unit 113 acquires the saturation determination value D30 from the saturation determination value setting unit 112 (S203). Regarding steps S201 to S203, all frames are processed. In addition, the fluorescence signal data D24 is also acquired frame by frame.

[0177] Next, the saturation determination unit 113 determines whether the maximum signal intensity of the analysis object sample signal D11 in the frame to be analyzed is equal to or greater than the saturation determination value D30 (S204).

[0178] When the maximum signal intensity is equal to or greater than the saturation determination value D30 (S204 → Yes), the saturation determination unit 113 attaches a saturation mark to the frame (S205).

[0179] In addition, in step S204, when the maximum signal intensity is less than the saturation determination value D30 (S204 → No), the saturation determination unit 113 performs the process of step S206.

[0180] In step S206, the saturation determination unit 113 determines whether the maximum signal intensity of the fluorescence signal data D24 in the frame to be processed is "32767" (RFU (Relative Fluorescence Unit)) or more. In step S206, it is determined whether saturation has occurred in the fluorescence signal data D24. Basically, if the analysis object sample signal D11 is lower than the saturation determination value D30, the fluorescence signal data D24 is not saturated. However, depending on the processing of the color conversion unit 103, sometimes the analysis object sample signal D11 is lower than the saturation determination value D30, but the fluorescence signal data D24 is saturated. Step S206 is performed to avoid such a situation. In addition, the value of "32767" (RFU) is half of the saturation charge amount of the summing gate 215. In this way, the reason why the saturation signal intensity of the fluorescence signal data D24 is half of the saturation charge amount of the summing gate 215 is that the fluorescence signal data D24 has positive and negative values.

[0181] When the maximum signal intensity of the fluorescence signal data D24 in the frame to be processed is 32767 (RFU) or more (S206 → Yes), the saturation determination unit 113 performs the process of step S205. In step S205, the saturation determination unit 113 assigns a saturation mark to the frame to be processed.

[0182] When the maximum signal intensity of the fluorescence signal data D24 in the frame to be processed is less than 32767 (RFU) (S206 → No), the saturation determination unit 113 performs the process of step S207. In step S207, the saturation determination unit 113 does not assign a saturation mark to the frame to be processed. That is, in step S207, the saturation determination unit 113 does not perform any processing.

[0183] Next, after performing the processes of steps S205 and S207, the saturation determination unit 113 determines whether the processing has been completed for all frames (S210).

[0184] When the processing has not been completed for all frames (S210 → No), the processing unit 10 performs the processes after step S204.

[0185] When the processing has been completed for all frames (S210 → Yes), the saturation determination unit 113 ends the saturation determination process.

[0186] In this way, when the signal intensity of the signal obtained from the measurement unit 20 exceeds the saturation determination value D30, the saturation determination unit 113 assigns a mark indicating that saturation has occurred in the obtained signal.

[0187] [Operation]

[0188] Next, with reference to Figures 13 - 15 , the operation of the first embodiment will be described.

[0189] In addition, in Figure 13 , Figure 14 , Figure 15 , Figure 17 , the frequency spectrum SP is shown for the case where the number of intervals B is 240. In addition, in Figure 13 , Figure 14 , Figure 15 , Figure 17 , the frequency spectrum SP of the analysis target sample signal D11 depicted in step S102 of Figure 11 is shown.

[0190] In addition, the first threshold value TH1 is used in step S103 of Figure 11 , and in Figure 13 , Figure 14 , Figure 15In the example shown, "20000" (ADU) is set as the first threshold TH1.

[0191] In addition, the spectrally separated light is incident on the light receiving elements 211A that make up each section B. Therefore, the signal intensity of light of different wavelengths is incident on each section B. Thus, in Figure 13 , Figure 14 , Figure 15 , Figure 17 the spectrum SP shown, the signal intensity corresponding to each section B represents the signal intensity of the light of the wavelength incident on that section B. Additionally, in Figure 13 , Figure 14 , Figure 15 , Figure 17 the example shown, the wavelength is shorter the closer to the left side of the paper surface, and the wavelength is longer the closer to the right side of the paper surface.

[0192] Figure 13 is a diagram showing an example of the spectrum SP1 where saturation does not occur.

[0193] Referring to Figure 13 , the maximum signal intensity in the spectrum SP1 (SP) is equal to or greater than the first threshold TH1 (the signal intensity "20000" (ADU) in the example of Figure 13 ). Therefore, in Figure 11 step S103, it is determined as "yes", and the saturation determination value setting unit 112 proceeds to the processing of Figure 11 step S104. Next, in Figure 11 step S104, the saturation determination value setting unit 112 determines whether the shape of the spectrum SP1 significantly deviates from the shape of a Gaussian distribution. Referring to Figure 13 , the spectrum SP1 becomes a distribution that does not significantly deviate from the shape of a Gaussian distribution. Therefore, the saturation determination value setting unit 112 determines as "no" in step S104. That is, the saturation determination value setting unit 112 determines that saturation does not occur in the frame and proceeds to Figure 11 step S109. Additionally, examples where the spectrum SP significantly deviates from the shape of a Gaussian distribution are described in Figure 14 , Figure 15 , Figure 17 .

[0194] Figure 14 is a diagram showing an example of the spectrum SP2 (SP) where saturation occurs in the summing gate 215.

[0195] Referring to Figure 14 , the maximum signal intensity is equal to or greater than the first threshold TH1 (the signal intensity "20000" (ADU) in the example of Figure 14 ). Therefore, the saturation determination value setting unit 112 determines as "yes" in Figure 11 step S103 and proceeds toFigure 11 processing of step S104. And, according to Figure 14 , the spectrum SP2(SP) has a flat top shape. Therefore, the shape of the spectrum SP2 becomes a shape that significantly deviates from the Gaussian distribution shape. Thus, the saturation determination value setting unit 112 determines "yes" in Figure 11 step S104 and proceeds to Figure 11 step S105. That is, the saturation determination value setting unit 112 determines that saturation has occurred. Then, the saturation determination value setting unit 112 records the lowest signal intensity in the portion where the signal intensity is approximately constant in step S105. In Figure 14 the example shown, the portion where the signal intensity is constant is only the top portion of the spectrum SP2. Therefore, the saturation determination value setting unit 112 records the signal intensity of the top portion of the spectrum SP2 (in Figure 14 the example shown is "65535" (ADU)). Then, the saturation determination value setting unit 112 sets the recorded value as the saturation determination value D30 ( Figure 11 S106). Then, the saturation determination value setting unit 112 outputs the set saturation determination value D30 to the saturation determination unit 113 ( Figure 11 S107). In addition, the portion where the signal intensity is approximately constant is determined, for example, as the portion where the difference in signal intensity between adjacent intervals B is within a predetermined range.

[0196] Figure 15 FIG. is an example of a spectrum SP3(SP) indicating that saturation has occurred in the charge storage element 213A.

[0197] Refer to Figure 15 the example shown, the maximum signal intensity is above the first threshold TH1 (in Figure 15 the example shown is the signal intensity "20000" (ADU)), so the saturation determination value setting unit 112 determines "yes" in Figure 11 S103. In addition, Figure 15 the shape of the spectrum SP3(SP) shown significantly deviates from the Gaussian distribution shape, so the saturation determination value setting unit 112 determines "yes" in Figure 11 step S104. That is, the saturation determination value setting unit 112 determines that saturation has occurred and performs Figure 11 the processing of step S105. In step S105, the saturation determination value setting unit 112 records the lowest signal intensity in the portion where the signal intensity is approximately constant. In Figure 15 the example shown, the portion where the signal intensity is approximately constant is only the top of the spectrum SP3. Therefore, in Figure 11In step S105, the saturation determination value setting unit 112 records the signal intensity at the top of the spectrum SP3, which is approximately "48000" (ADU), as the saturation determination value D30.

[0198] Figure 16 It is a diagram showing an example of an electrophoresis image.

[0199] Figure 16 It is a curve graph plotted with the horizontal axis representing the frame number and the vertical axis representing the maximum signal intensity of the frame. Figure 16 A curve graph plotted with the horizontal axis representing the frame number and the vertical axis representing the maximum signal intensity of the frame as described above is called an electrophoresis image. The horizontal axis corresponds to time. In addition, Figure 16 the frame numbers "4000" to "5500" are shown.

[0200] In Figure 16 the example shown, peaks D51 to D56 appear in order from the left side of the paper surface. The saturation determination unit 113 determines whether saturation has occurred in each frame based on the saturation determination value D30 set by the saturation determination value setting unit 112. In addition, Figure 12 in step S203 of Figure 16 the saturation determination unit 113 acquires the saturation determination value D30 output by the saturation determination value setting unit 112. In Figure 16 the example shown, approximately "48000" (ADU) is set as the saturation determination value D30. In Figure 12 the example shown, the three peaks D53, D55, and D56 reach the saturation determination value D30 (approximately "48000" (ADU)) Figure 12 ("Yes" in S204 of

[0201] Therefore, the saturation determination unit 113 determines that saturation has occurred in the frames having peaks D53, D55, and D56. Therefore, the saturation determination unit 113 Figure 17 is a diagram showing an example of the spectrum SP4 (SP) in the first - 1 embodiment.

[0202] Figure 17 is the spectrum SP4 (SP) drawn in step S102 of Figure 11 In the spectrum SP4 shown in Figure 17 the signal intensity is definitely around the signal intensity "48000" (ADU) (first - stage saturation: symbol SR1), similar to Figure 15 However, in Figure 17In the spectrum SP shown, beyond the saturation of the first stage (symbol SR1: signal intensity around "48000"), the signal intensity must again be around the signal intensity "60000" (ADU) (saturation of the second stage: symbol SR2). And, in Figure 17 In the spectrum SP shown, beyond the saturation of the second stage (symbol SR2: signal intensity around "60000" (ADU)), the signal intensity must again be the signal intensity "65535" (ADU) (saturation of the third stage: symbol SR3). That is, in Figure 17 In the spectrum SP shown, saturation occurs in multiple stages (in Figure 17 the example shown, it is 3 stages).

[0203] In Figure 15 , the reliable value is the signal intensity around "48000" (ADU) which is the saturation of the first stage (symbol SR1). That is, as the saturation determination value D30, it is preferable to set the signal intensity as low as possible. In step S105, the lowest signal intensity in the portion where the signal intensity is roughly constant is recorded. Through this process, in the case of obtaining Figure 15 the spectrum SP4 as shown, the saturation determination value setting unit 112 records the signal intensity "48000" (ADU) indicated by the symbol SR1 as the saturation determination value D30. Therefore, the saturation determination value setting unit 112 can record a highly reliable saturation determination value D30.

[0204] [Effect]

[0205] In Patent Document 1, saturation is determined only when the signal intensity is "65535" (ADU) or more (signal intensity based on the saturation charge amount of the summing gate 215). However, in the method described in Patent Document 1, in the case of obtaining Figure 15 the spectrum SP3 as shown, saturation cannot be determined. Additionally, in the case of obtaining Figure 17 the spectrum SP4 as shown, in the method of Patent Document 1, only the symbol SR3 is used as the determination value for detecting the presence or absence of saturation. And, in the technology described in Patent Document 1, the highly reliable symbol SR1 is not used as the determination value for detecting the presence or absence of saturation. The same applies to the technology described in Patent Document 2.

[0206] However, according to the 1-1 Embodiment, the saturation determination value setting unit 112 determines whether the shape of the spectrum SP significantly deviates from the shape of the Gaussian distribution ( Figure 11 S104). Thereby, the saturation determination value setting unit 112 sets the signal intensity at saturation (saturation determination value D30) ( Figure 11 S106). Thereby, even in the case of obtaining Figure 15In the case of the spectrum SP3 shown, an appropriate saturation determination value D30 can also be obtained.

[0207] In Figure 11 the flowchart shown, the saturation determination value setting unit 112 determines whether the shape of the spectrum SP significantly deviates from the Gaussian distribution (S104). In addition, the saturation determination value setting unit 112 records the lowest signal intensity in the portion where the signal intensity is substantially constant in the spectrum SP (S105). By performing such processing, even when a spectrum SP4 as shown in Figure 17 which saturates at multiple stages is obtained, the signal intensity corresponding to the symbol SR1 can be set as the saturation determination value D30 (S106).

[0208] By changing the size of the interval B in this way, the amount of charge that saturates is different. In addition, the presence or absence of saturation also changes according to the saturated charge amount in the light receiving element 211A.

[0209] The reason why the saturation determination value D30 is different according to the CCD image sensor 210 is that the saturated charge amounts of the charge storage element 213A, the horizontal register 214A, and the summing gate 215 are different according to the CCD image sensor 210.

[0210] Next, with reference to Figures 18A - 19C , an example in which the presence or absence of saturation changes by changing the size of the interval B will be described.

[0211] Figures 18A - 18C is a schematic diagram showing the case of saturation when the interval B is composed of nine light receiving elements 211A.

[0212] In Figures 18A - 18C , the thin arrows indicate the charge transfer direction. In addition, time passes in the order of Figures 18A - 18C . And, as in the description in Figures 5 - 7 , the saturated charge amount of the charge storage element 213A is "320ke - ", and the saturated charge amount of the summing gate 215 is "1000ke - ".

[0213] Assume that light is irradiated on the light receiving element 211A (refer to Figure 3 ), and charges of "120ke - " are respectively stored in the charge storage elements 213A corresponding to the light receiving element 211A ( Figure 18A ). At this time, saturation does not occur in the charge storage element 213A. The charges stored in each charge storage element 213A are transferred to the horizontal register 214A. When the charges of all the charge storage elements 213A in the interval B are transferred to the horizontal register 214A, as in Figure 18BAs shown, the charge of "360ke" is accumulated in each horizontal register 214A. - As described Figures 5 - 7 below, the charge accumulated in the horizontal register 214A is transferred to the summing gate 215. When the charge of all the horizontal registers 214A in interval B is completely transferred to the summing gate 215, as Figure 18C shown, in the summing gate 215, the charge is accumulated to "1080ke". - Here, the saturation charge amount of the summing gate 215 is "1000ke". - Therefore, saturation occurs in the summing gate 215. That is, in the example shown Figures 18A - 18C below, saturation does not occur in the charge storage element 213A, but saturation occurs in the summing gate 215.

[0214] Next, with reference to Figures 19A - 19C the case where saturation occurs in the charge storage element 213A and saturation does not occur in the summing gate 215 will be described.

[0215] On the other hand, in Figures 19A - 19C the case where interval B is composed of three light receiving elements 211A in the vertical direction is described. Such an interval B can be realized by applying a pulse to the charge storage section 213 three times and applying a pulse to the horizontal register section 214 once as one interval B. That is, in Figures 19A - 19C compared with Figures 18A - 18C interval B is set smaller.

[0216] In Figures 19A - 19C the thin arrow indicates the transfer direction of the charge. In addition, time passes in the order of Figures 19A - 19C . And in Figures 19A - 19C the saturation charge amount of the summing gate 215 is "1000ke" as described in Figures 5 - 7 . In addition, in - the saturation charge amount of the charge storage element 213A is "320ke" as described above. Figures 19A - 19C In - as described above.

[0217] Assume that strong light is irradiated on the light receiving element 211A. Strong light means strong light that generates charge exceeding the saturation charge amount in the charge storage element 213A in the light receiving element 211A. In such a case, as Figure 19A shown, the saturation charge amount of the charge storage element 213A corresponding to the light receiving element 211A is "320ke". - Therefore, "320ke" is accumulated in each charge storage element 213A. -” of charge. Then, the charge accumulated through the above-described process is transferred from the charge accumulation unit 213 to the horizontal register 214A. When the charge of all the charge accumulation elements 213A in section B is transferred to the horizontal register 214A, "960ke - ” of charge is accumulated in the horizontal register 214A (see Figure 19B ). Also, the charge accumulated in the horizontal register 214A is transferred to the summing gate 215 (see Figure 19C ). As a result, "960ke - ” is accumulated in the summing gate 215. As described above, the saturation charge amount of the summing gate 215 is "1000ke - ”, so in the example shown in Figure 19C , saturation does not occur in the summing gate 215. That is, in the example shown in Figures 19A - 19C , saturation occurs in the charge accumulation element 213A and does not occur in the summing gate 215.

[0218] Thus, when the light receiving element 211A is irradiated with strong light in a state where section B is set small, a phenomenon occurs where saturation occurs in the charge accumulation element 213A but does not occur in the summing gate 215. In such a case, the obtained spectrum SP becomes the spectrum SP3 as shown in Figure 15 . In the prior art including Patent Documents 1 to 2, when a phenomenon occurs where saturation occurs in the charge accumulation element 213A but does not occur in the summing gate 215, saturation cannot be detected. According to the 1-1st Embodiment, based on the shape of the spectrum SP, it is determined whether saturation occurs. Thus, even in the case where saturation occurs in the charge accumulation element 213A but does not occur in the summing gate 215 as shown in Figures 19A - 19C , the occurrence of saturation can be detected.

[0219] According to the 1-1st Embodiment, as shown in Figures 18A - 18C , Figures 19A - 19CAs in the example shown, even when the size of interval B changes and the saturation charge amount changes, it is possible to determine the presence or absence of saturation of the signal D11 of the sample to be analyzed. In addition, according to the first-1 embodiment, even when using a CCD image sensor 210 with a small saturation charge amount, it is possible to determine saturation. That is, since the saturation charge amount of the charge storage element 213A is small, even when using a CCD image sensor 210 in which the charge storage element 213A is saturated, it is possible to determine saturation. That is, it is possible to determine saturation regardless of the difference in the saturation charge amount between the measurement unit 20 used. Specifically, even if the saturation charge amounts of the CCD image sensor 210 and the horizontal register 214A change due to replacement of the measurement unit 20 or the like, it is possible to determine the presence or absence of saturation without investigating the characteristics of the CCD image sensor 210 and the horizontal register 214A.

[0220] Thus, according to the first-1 embodiment, it is possible to prevent misidentifying a signal that is actually saturated as unsaturated. Therefore, according to the first-1 embodiment, it is possible to eliminate the possibility of misidentifying a signal that is actually saturated as unsaturated and using it for diagnosis or the like. That is, according to the first-1 embodiment, it is possible to improve the determination accuracy of the presence or absence of saturation in the measurement unit of the electrophoresis apparatus.

[0221] Moreover, according to the first-1 embodiment, even when the shape of the spectrum SP of the matrix standard D20 is not known in advance, it is possible to determine saturation based on a comparison with the shape of the Gaussian distribution.

[0222] In addition, the method described in the first-1 embodiment can be implemented by changing the program of the processing unit 10. Therefore, it is possible to implement the method described in the first-1 embodiment without changing the structure of the measurement unit 20, thus saving costs.

[0223] Furthermore, according to the method described in the first-1 embodiment, even when the specifications of a newly purchased CCD image sensor 210 are unknown, it is possible to determine whether saturation has occurred.

[0224] <The first-2 embodiment>

[0225] Next, Figures 20 - 22 the first-2 embodiment of the present invention will be described.

[0226] In the first-1 embodiment, a saturation determination value D30 is set in the saturation determination value setting unit 112, and saturation is determined based on whether the maximum signal intensity of the signal D11 of the sample to be analyzed is equal to or greater than the saturation determination value D30.

[0227] In contrast, in the first-2 embodiment, the spectrum generation unit 111 depicts a spectrum SP in all frames of the signal D11 of the sample to be analyzed (refer toFigure 13 )。Then, the saturation determination unit 113 determines whether saturation occurs in each frame based on the shape of the spectrum SP.

[0228] [System Structure]

[0229] Figure 20 FIG. is a schematic diagram showing the structure of the electrophoresis apparatus 1 in the first to second embodiments.

[0230] As Figure 20 shown, the electrophoresis apparatus 1 includes a measurement unit 20 and a processing unit 10.

[0231] The processing unit 10 mainly includes: a fluorescence correction unit 101, a color conversion unit 103, a spectrum generation unit 111, and a saturation determination unit 113.

[0232] The fluorescence correction unit 101 and the color conversion unit 103 perform the same processing as in the first to first embodiments.

[0233] The processing performed by the spectrum generation unit 111 and the saturation determination unit 113 will be described later in the operation items.

[0234] Figure 21 FIG. is a diagram showing a detailed structural example of the processing unit 10 in the first to second embodiments.

[0235] In Figure 21 it, the difference from the structure shown in Figure 4 is that the saturation determination value setting unit 112 is omitted.

[0236] As Figure 21 shown, the measurement unit 20 outputs an analysis target sample signal D11 from the analysis target sample D10 to the processing unit 10. In addition, the measurement unit 20 outputs a matrix standard signal D21 derived from the matrix standard D20 to the processing unit 10.

[0237] Then, the fluorescence correction unit 101 of the processing unit 10 acquires the digital signal of the matrix standard D20. In addition, the color conversion unit 103 acquires the digital signal of the matrix standard D20 and the analysis target sample signal D11. And the spectrum generation unit 111 acquires the analysis target sample signal D11.

[0238] The operation of the fluorescence correction unit 101 is the same as that in the first to first embodiments.

[0239] The pseudo-inverse matrix generation unit 102 acquires the fluorescence spectrum data D22 from the fluorescence correction unit 101 and generates a pseudo-inverse matrix D23 of the fluorescence spectrum data D22.

[0240] Then, the color conversion unit 103 multiplies the analysis target sample signal D11 obtained from the measurement unit 20 by the pseudo-inverse matrix D23 generated by the pseudo-inverse matrix generation unit 102. Thereby, the fluorescence signal data D24 is generated.

[0241] Based on the analysis target sample signal D11 obtained from the measurement unit 20, the spectrum generation unit 111 generates a spectrum SP (refer to Figure 13 ).

[0242] Based on the generated spectrum SP and the fluorescence signal data D24, the saturation determination unit 113 determines frame by frame whether saturation has occurred in the analysis target sample signal D11.

[0243] [Saturation determination process]

[0244] Next, refer to Figure 22 to describe the processing procedure of the electrophoresis data processing method in the first to second embodiments.

[0245] Figure 22 is a flowchart showing the process of the saturation determination process of the saturation determination unit 113 in the first to second embodiments.

[0246] First, the spectrum generation unit 111 obtains the analysis target sample signal D11 from the measurement unit 20 (S301). In step S301, the analysis target sample signal D11 is obtained for all frames. Step S301 corresponds to the signal acquisition step.

[0247] Next, for all frames, the spectrum generation unit 111 depicts (generates) the spectrum SP of the analysis target sample signal D11 frame by frame (refer to Figure 13 )(S302). The spectrum SP is a curve graph configured with the horizontal axis as the interval B number and the vertical axis as the signal intensity of the interval B as described above. Step S302 corresponds to the spectrum generation step.

[0248] Next, the saturation determination unit 113 selects one of the frames. Then, for the selected frame, the saturation determination unit 113 determines whether the maximum signal intensity of the spectrum SP depicted in step S302 is equal to or greater than the first threshold TH1 (refer to Figure 13 )(S303). The first threshold TH1 is the same as the first threshold TH1 used in the first to first embodiments.

[0249] When the maximum signal intensity of the spectrum SP is equal to or greater than the first threshold TH1 (S303 → Yes), the saturation determination unit 113 determines whether the shape of the spectrum SP depicted in step S302 significantly deviates from the shape of the Gaussian distribution (S304). The determination of whether it significantly deviates from the shape of the Gaussian distribution is performed by the same method as in Figure 11 step S104. Step S304 corresponds to the saturation determination step.

[0250] When the shape of the spectrum SP significantly deviates from the Gaussian distribution shape (S304 → Yes), the saturation determination unit 113 assigns a saturation mark to the frame to be processed (S305).

[0251] When the shape of the spectrum SP does not significantly deviate from the Gaussian distribution shape (S304 → No), the saturation determination unit 113 does not assign a saturation mark to the frame to be processed (S306).

[0252] In addition, in step S303, when the maximum signal intensity of the spectrum SP is less than the first threshold TH1 (S303 → No), the saturation determination unit 113 does not assign a saturation mark to the frame to be processed (S306). That is, in step S306, the saturation determination unit 113 does not perform any processing.

[0253] After performing the processes of steps S305 and S306, the saturation determination unit 113 determines whether the processing has been completed for all frames (S310).

[0254] When the processing has not been completed for all frames (S310 → No), the processing unit 10 performs the processing after step S303.

[0255] When the processing has been completed for all frames (S310 → Yes), the saturation determination unit 113 ends the saturation determination process.

[0256] [Function]

[0257] The case where the spectrum SP depicted in step S302 is the spectrum SP1 as shown in Figure 22 has been described. Figure 13 The maximum signal intensity of the spectrum SP1 shown is equal to or greater than the first threshold TH1 (in the example shown in Figure 13 it is "20000" (ADU)). Therefore, the saturation determination unit 113 determines "Yes" in step 303 of Figure 13 . Then, in step S304, the saturation determination unit 113 determines whether the shape of the spectrum SP significantly deviates from the Gaussian distribution shape. Figure 22 The example of the spectrum SP shown does not significantly deviate from the Gaussian distribution shape. Therefore, the saturation determination unit 113 determines "No" in step S304 of Figure 13 . Through such a process, the saturation determination unit 113 determines that saturation has not occurred in the spectrum SP shown in Figure 22 . Therefore, in step S306 of Figure 13 , the saturation determination unit 113 does not assign a saturation mark to the frame to be processed. Figure 22 In

[0258] Next, the case where the spectrum SP depicted in step S302 of Figure 22 is the spectrum SP2 as shown in Figure 14 will be described.

[0259] In the example shown in Figure 14 , since the maximum signal intensity is equal to or greater than the first threshold TH1 (“20000” (ADU)), the saturation determination unit 113 determines “yes” in step S303 of Figure 22 . Also, in step S304 of Figure 22 , Figure 14 the spectrum SP2 shown in is in a shape with a flat top and is a shape that significantly deviates from a Gaussian distribution. Therefore, the saturation determination unit 113 determines “yes” in step S304 of Figure 22 . Thus, the saturation determination unit 113 determines that saturation has occurred in the frame to be processed. Then, in step S305 of Figure 22 , the saturation determination unit 113 assigns a saturation mark to the frame to be processed.

[0260] Next, the case where the spectrum SP depicted in step S302 of Figure 22 is the spectrum SP3 as shown in Figure 15 will be described. In the example shown in Figure 15 , since the maximum signal intensity is equal to or greater than the first threshold TH1 (“20000” (ADU)), the saturation determination unit 113 determines “yes” in step S303 of Figure 22 . Also, in the example of the spectrum SP3 shown in Figure 15 , it is in a shape with a flat top. That is, Figure 15 the spectrum SP3 shown in is a shape that significantly deviates from a Gaussian distribution. Therefore, the saturation determination unit 113 determines “yes” in step S304 of Figure 22 . In this way, the saturation determination unit 113 determines that saturation has occurred in the frame to be processed. The saturation determination unit 113 assigns a saturation mark to the frame to be processed in step S305.

[0261] In this way, in the first to second embodiments, based on the shape of the spectrum SP, when it is determined that saturation has occurred in the measurement unit 20, the saturation determination unit 113 assigns a mark indicating that saturation has occurred to the acquired signal.

[0262] [Effect]

[0263] According to the first to second embodiments, in addition to the effects of the first to first embodiments, saturation can be determined without providing a saturation determination value setting unit 112. That is, the processing load can be reduced.

[0264] [First to Third Embodiments]

[0265] In the first first embodiment, when the saturation determination value setting unit 112 sets the saturation determination value D30, the analysis target sample signal D11 is used. In the first third embodiment, instead, the saturation reference sample signal D41, which is a digital signal (signal) of the saturation reference sample D40, is used. The saturation reference sample D40 is a sample with a sufficiently high concentration to intentionally cause saturation in the charge storage unit, i.e., to the extent that saturation occurs. That is, when electrophoresis is performed using the saturation reference sample D40, it can be generally determined that a certain saturation has occurred.

[0266] [Processing unit 10]

[0267] Figure 23 FIG. shows the structure of the processing unit 10 in the first third embodiment.

[0268] Figure 23 The processing unit 10 shown is different from Figure 4 the processing unit 10 shown in that the saturation determination value setting unit 112 uses the saturation reference sample signal D41 to set the saturation determination value D30.

[0269] In the first third embodiment, the analysis target sample D10, the matrix standard D20, and the saturation reference sample D40 are used. And, in the first third embodiment, before electrophoresis of the analysis target sample D10 and the matrix standard D20, electrophoresis of the saturation reference sample D40 is performed.

[0270] Then, the measurement unit 20 outputs the saturation reference sample signal D41 obtained by electrophoresis of the saturation reference sample D40 to the processing unit 10.

[0271] In addition, the measurement unit 20 outputs the analysis target sample signal D11 to the processing unit 10. And the measurement unit 20 outputs the matrix standard signal D21 to the processing unit 10.

[0272] The fluorescence correction unit 101 acquires the matrix standard signal D21. Then, the pseudo-inverse matrix generation unit 102 generates a pseudo-inverse matrix D23 of the fluorescence spectrum data D22. In addition, the color conversion unit 103 acquires the pseudo-inverse matrix D23 generated by the pseudo-inverse matrix generation unit 102 and the analysis target sample signal D11, and generates fluorescence signal data D24 based on these data.

[0273] In this way, the operations of the fluorescence correction unit 101, the pseudo-inverse matrix generation unit 102, the color conversion unit 103, and the saturation determination unit 113 are the same as those in the first first embodiment.

[0274] The spectrum generation unit 111 acquires the saturation reference sample signal D41 and generates a spectrum SP of the saturation reference sample signal D41.

[0275] Based on the generated spectrum SP, the saturation determination value setting unit 112 sets the saturation determination value D30. The saturation determination value setting unit 112 outputs the set saturation determination value D30 to the saturation determination unit 113. The operation performed by the saturation determination value setting unit 112 will be described later.

[0276] The saturation determination unit 113 acquires the analysis target sample signal D11, the fluorescence signal data D24, and the saturation determination value D30 set by the saturation determination value setting unit 112. Then, based on the saturation determination unit 113 and the fluorescence signal data D24, the saturation determination unit 113 assigns a saturation mark to the analysis target sample signal D11.

[0277] [Flowchart]

[0278] Next, refer to Figure 24 The processing procedure of the electrophoresis data processing method in the first to third embodiments will be described.

[0279] Figure 24 It is a flowchart showing the process of the saturation determination value setting process of the saturation determination value setting unit 112 in the first to third embodiments. Refer to appropriately Figure 23 .

[0280] First, the spectrum generation unit 111 acquires the saturation reference sample signal D41 from the measurement unit 20 (S401). In addition, the merged result of the saturation reference sample signal D41 is also output.

[0281] Next, for the saturation reference sample signal D41 acquired in step S401, the spectrum generation unit 111 depicts the spectrum SP frame by frame (refer to Figure 13 )(S402). As before, the spectrum SP is depicted with the horizontal axis being the number of the interval B and the vertical axis being the signal intensity of the interval B. The spectrum SP depicted in step S402 is a spectrum SP generated based on the signal intensity obtained from the result of measuring the saturation reference sample D40 by the measurement unit 20.

[0282] Next, the saturation determination value setting unit 112 selects one of the frames. Then, for the selected frame, the saturation determination value setting unit 112 determines whether the maximum signal intensity of the spectrum SP depicted in step S402 is equal to or greater than the first threshold TH1 (refer to Figure 13 )(S403). The first threshold TH1 is the same as the first threshold TH1 used in the first to first embodiments.

[0283] When the maximum signal intensity of the spectrum SP is equal to or greater than the first threshold TH1 (S403 → Yes), the saturation determination value setting unit 112 determines whether the shape of the spectrum SP depicted in step S402 significantly deviates from the shape of a Gaussian distribution (S404). In step S404, through the same processing as in Figure 11 step S104, the saturation determination value setting unit 112 determines whether the shape of the spectrum SP depicted in step S402 significantly deviates from the shape of a Gaussian distribution.

[0284] When the shape of the spectrum SP significantly deviates from the shape of a Gaussian distribution (S404 → Yes), the saturation determination value setting unit 112 determines that saturation has occurred in the measurement unit 20 and executes the processing of step S405. In step S405, the saturation determination value setting unit 112 records the lowest signal intensity in the portion of the spectrum SP where the signal intensity is approximately constant.

[0285] Next, the saturation determination value setting unit 112 sets the value of the signal intensity recorded in step S405 as the saturation determination value D30 (S406) and outputs the set saturation determination value D30 to the saturation determination unit 113 (S407).

[0286] In addition, in step S403, when the maximum signal intensity of the spectrum SP is less than the first threshold TH1 (S403 → No), the processing unit 10 proceeds to the next frame (S408) and performs the processing after step S403.

[0287] Then, in step S404, when the shape of the spectrum SP does not significantly deviate from the shape of a Gaussian distribution (S404 → No), the saturation determination value setting unit 112 performs the processing of step S409. In step S409, the saturation determination value setting unit 112 determines whether the frame to be processed is the final frame.

[0288] When the frame to be processed is not the final frame (S409 → No), the processing unit 10 proceeds to the next frame (S410) and performs the processing after step S403. In addition, the reason for performing the Figure 24 processing on multiple frames is that it is unknown at which timing the saturation reference sample D40 is detected (when the saturation reference sample D40 reaches the fluorescence detection position 24).

[0289] When the frame to be processed is the final frame (S409 → Yes), the user increases (makes thicker) the concentration of the saturation reference sample D40 (S411). Then, in step S411, the user performs electrophoresis on the saturation reference sample D40 with the changed concentration again (S412). The determination of "Yes" in step S409 indicates that saturation has not occurred in the saturation reference sample D40 adjusted to intentionally cause saturation. Therefore, after adjusting the concentration of the saturation reference sample D40 again, electrophoresis of the saturation reference sample D40 is performed (S411 - S412). As described above, the saturation reference sample D40 is a sample with a concentration high enough to be saturated, so it is difficult to think that saturation does not occur. However, in order to deal with the case where saturation does not occur due to an error in the preparation of the saturation reference sample D40, etc., the processes of steps S411 - S412 are performed.

[0290] After electrophoresis is performed again in step S412, the processing unit 10 performs the processing of step S401 and below.

[0291] In addition, the operation of the saturation determination unit 113 in the first to third embodiments is the same as Figure 12 the processing shown, so the illustration and description are omitted.

[0292] [Function]

[0293] The case where the spectrum SP depicted in step S402 in the first to third embodiments is Figure 13 the spectrum SP1 as shown will be described. Figure 13 Since the maximum signal intensity of the spectrum SP1 shown is equal to or higher than the first threshold TH1 ("20000" (ADU)), the saturation determination value setting unit 112 determines "Yes" in Figure 24 S403. Then, in Figure 24 step S404, the saturation determination value setting unit 112 determines whether the shape of the spectrum SP significantly deviates from the shape of a Gaussian distribution. Figure 13 The example of the spectrum SP1 shown is a shape that does not significantly deviate from the shape of a Gaussian distribution, so the saturation determination value setting unit 112 determines "No" in Figure 24 step S404. That is, the saturation determination value setting unit 112 determines that saturation has not occurred in the frame to be processed.

[0294] Next, the saturation determination value setting unit 112 determines whether the frame to be processed is the final frame ( Figure 24 S409). When it is the final frame (S409 → Yes), when the user increases (thickens) the concentration of the saturation reference sample D40 (S411), electrophoresis of the saturation reference sample D40 is performed again.

[0295] In addition, when the frame to be processed is not the final frame ( Figure 24 S409 → No), the processing unit 10 proceeds to the next frame ( Figure 24 S410).

[0296] In addition, the processing performed by the saturation determination unit 113 is the same as the processing Figure 12 shown. Therefore, in the second to third embodiments, the description of the processing of the saturation determination unit 113 is omitted. However, in the first to third embodiments, after re-performing electrophoresis on the analysis target sample D10, the processing Figure 12 shown is performed.

[0297] In addition, a case where the spectrum SP depicted in step S402 of ​ is the spectrum SP3 as ​ shown will be described. In the spectrum SP3 shown in ​ , the maximum signal intensity is equal to or greater than the first threshold TH1 (in the example shown in ​ it is "20000" (ADU)). Therefore, the saturation determination value setting unit 112 determines "Yes" in step S403 of ​ . In addition, in step S404 of ​ , the spectrum SP shown in ​ has a flat top shape and is a shape that significantly deviates from the Gaussian distribution. Therefore, the saturation determination value setting unit 112 determines "Yes" in step S404 of ​ . That is, the saturation determination value setting unit 112 determines that saturation has occurred in the frame to be processed. Then, in step S405 of ​ , the saturation determination value setting unit 112 records the lowest signal intensity in the portion where the signal intensity at the top of the spectrum SP is approximately constant (in the example shown in ​ , it is approximately "48000" (ADU)). Then, the saturation determination value setting unit 112 sets the recorded value as the saturation determination value D30 ( ​ S406). And the saturation determination value setting unit 112 outputs the set saturation determination value D30 to the saturation determination unit 113 ( ​ S407).

[0298] <First to Third Embodiments: Effects>

[0299] In the 1-1 embodiment, the saturation determination value D30 is set each time electrophoresis is performed. This is because the analysis target sample D10 is usually not saturated, and even if saturated, saturation in the charge storage element 213A may not necessarily occur. In contrast, in the 1-3 embodiment, in addition to the effects of the 1-1 embodiment, the saturation determination value D30 can be roughly determined by performing electrophoresis on the saturated reference sample D40 only once.

[0300] In the first embodiment, the spectrum SP of the analysis target sample signal D11 and the saturation reference sample signal D41 is compared with a Gaussian distribution of a predetermined shape. Then, the saturation judgment value setting unit 112 and the saturation judgment unit 113 judge that saturation has occurred in the measurement unit when the shape of the spectrum SP deviates from the shape of the Gaussian distribution.

[0301] Second Implementation Method

[0302] In the first embodiment, according to the spectrum SP (refer to ​ ) deviates significantly from the shape of the Gaussian distribution, and determines whether saturation has occurred in the frame to be processed. In the second embodiment to the second embodiment shown below, whether saturation has occurred in the interval B to be processed is determined based on the change in the slope of the shape of the spectrum SP.

[0303] <Implementation Method 2-1>

[0304] [System Structure]

[0305] The system configuration of the second embodiment is different from that of the first embodiment except that the saturation determination value setting unit 112 determines the presence or absence of saturation based on the change in the slope of the shape of the spectrum SP. ​ Therefore, the illustration of the system configuration in the 2-1 embodiment is omitted.

[0306] [flow chart]

[0307] Next, refer to ​ , the processing process of the electrophoresis data processing method in embodiment 2-1 is explained.

[0308] ​ 2-1 is a flowchart showing the process of setting the saturation determination value in the embodiment. ​ .

[0309] First, the spectrum generating unit 111 acquires the analysis target sample signal D11 from the measuring unit 20 (S501). Step S501 corresponds to a signal acquiring step.

[0310] Next, the spectrum generation unit 111 depicts (generates) a spectrum SP for each frame of the sample signal D11 to be analyzed (refer to ​ )(S502). In step S502, the spectrum SP of the sample signal D11 to be analyzed is depicted for all frames. Step S502 corresponds to the spectrum generation step.

[0311] Next, the saturation determination value setting unit 112 selects one of the frames. Then, the saturation determination value setting unit 112 determines whether the maximum signal intensity of the spectrum SP depicted in step S502 for the selected frame is equal to or greater than the first threshold TH1 (refer to ​ )(S503). The first threshold TH1 is the same as the first threshold TH1 used in the first embodiment.

[0312] When the maximum signal intensity of the spectrum SP is less than the first threshold TH1 (S503 → No), the processing unit 10 moves to the next frame (S509) and performs the processing after step S503.

[0313] When the maximum signal intensity of the spectrum SP is equal to or greater than the first threshold TH1 (S503 → Yes), the saturation determination value setting unit 112 calculates the absolute value DIF of the second derivative of the spectrum SP for the frame to be processed (refer to ​ )(S504). The absolute value DIF of the second derivative is the absolute value of the value obtained by performing a second derivative on the spectrum SP. In addition, the absolute value DIF of the second derivative is calculated for the interval B. That is, the absolute value DIF of the second derivative

[0314] Next, the saturation determination value setting unit 112 determines whether the maximum value (maximum absolute value of the second derivative) of the absolute value DIF of the second derivative calculated in step S504 is equal to or greater than a predetermined threshold, i.e., the second threshold TH2 (refer to ​ )(S505). As the second threshold TH2, a value is preset that is sufficiently smaller than the maximum absolute value of the second derivative when saturation occurs and sufficiently larger than the maximum absolute value of the second derivative when saturation does not occur. Step S505 corresponds to the saturation determination step.

[0315] When the maximum absolute value of the second derivative is equal to or greater than the second threshold TH2 (S505 → Yes; when exceeding the predetermined threshold), the saturation determination value setting unit 112 determines that saturation has occurred in the measurement unit 20 and performs the processing of step S506. In step S506, the saturation determination value setting unit 112 records the lowest signal intensity in the portion of the spectrum SP where the signal intensity is substantially constant. That is, when the maximum absolute value of the second derivative is equal to or greater than the second threshold TH2 (S506 → Yes), the saturation determination value setting unit 112 determines that saturation has occurred in the signal obtained from the measurement unit 20.

[0316] Next, the saturation determination value setting unit 112 sets the value of the signal strength recorded in step S506 as the saturation determination value D30 (S507), and outputs the set saturation setting value to the saturation determination unit 113 (S508).

[0317] In step S505, when the absolute value of the maximum second derivative is less than the second threshold TH2 (S505 → NO), the saturation determination value setting unit 112 performs the process of step S510. In step S510, the saturation determination value setting unit 112 determines whether the frame to be processed is the final frame.

[0318] When the frame to be processed is the final frame (S510 → YES), the saturation determination value setting unit 112 records the signal strength "65535" (ADU) (S511).

[0319] Then, the saturation determination value setting unit 112 sets the value "65535" (ADU) recorded in step S511 as the saturation determination value D30 (S507). Then, the saturation determination value setting unit 112 outputs the saturation determination value D30 set in step S507 to the saturation determination unit 113 (S508).

[0320] In step S510, when the frame to be processed is not the final frame (S510 → NO), the processing unit 10 moves to the next frame (S512) and performs the processing after step S503.

[0321] The operation of the saturation determination unit 113 in the 2-1st embodiment is the same as the ​ processing shown, so the description in the 2-1st embodiment is omitted.

[0322] [Function]

[0323] Regarding the case where the frequency spectrum SP depicted in step S502 of ​ is the frequency spectrum SP1 as shown in ​ will be described.

[0324] In ​ the example of the frequency spectrum SP1 shown, the maximum signal strength is equal to or greater than the first threshold TH1 (in the example shown in ​ it is "20000" (ADU)). Therefore, the saturation determination value setting unit 112 determines "YES" in step S503 of ​ . Next, in step S504 of ​ , the saturation determination value setting unit 112 calculates the absolute value of the second derivative DIF of the frequency spectrum SP for the frame to be processed (refer to ​ ).

[0325] ​It represents ​ A graph of the spectrum SP1 shown and the absolute value of the second derivative DIF related to the spectrum SP1.

[0326] Figure 26 The spectrum SP1 shown by the dashed line in Figure 13 Is the same as the spectrum SP1 shown.

[0327] In Figure 26 In the example shown, the maximum value of the absolute value of the second derivative DIF (the maximum absolute value of the second derivative) is less than the second threshold TH2. Therefore, the saturation determination value setting unit 112 determines "no" in Figure 25 Step S505. That is, the saturation determination value setting unit 112 determines that saturation has not occurred in the frame to be processed.

[0328] Then, the saturation determination value setting unit 112 determines whether the frame to be processed is the final frame (S510). If it is the final frame (S510 → yes), the saturation determination value setting unit 112 records "65535" (ADU) (S511). Then, if it is not the final frame (S510 → no), the processing unit 10 proceeds to the next frame (S512).

[0329] In addition, for the case where the spectrum SP depicted in Figure 25 Step S502 is the spectrum SP3 as shown in Figure 15 Is described. In the spectrum SP3 shown in Figure 15 The maximum signal intensity is above the first threshold TH1 ("20000" (ADU)). Therefore, the saturation determination value setting unit 112 determines "yes" in Figure 25 Step S503.

[0330] Figure 27 It represents Figure 15 A graph of the spectrum SP3 shown and the absolute value of the second derivative DIF related to the spectrum SP3.

[0331] According to Figure 27 In the example shown, the maximum value of the absolute value of the second derivative DIF related to the spectrum SP3 (the maximum absolute value of the second derivative) is above the second threshold TH2. Therefore, the saturation determination value setting unit 112 determines "yes" in Figure 25 Step S505. That is, the saturation determination value setting unit 112 determines that saturation has occurred in the frame to be processed. Then, the saturation determination value setting unit 112 records the lowest signal intensity in the portion where the signal intensity is substantially constant in Figure 25 Step S506. In Figure 26In the example shown, the portion where the signal strength is approximately constant is only the top of the spectrum SP3. Therefore, the saturation determination value setting unit 112 records the signal strength at the top of the spectrum SP3 (in Figure 27 the example shown, it is approximately "48000" (ADU)). Then, the saturation determination value setting unit 112 sets the value recorded in step S506 as the saturation determination value D30 ( Figure 25 in S507). Then, the saturation determination value setting unit 112 outputs the set saturation determination value D30 to the saturation determination unit 113 ( Figure 25 in S508).

[0332] In the spectrum SP of a frame where saturation has not occurred, it changes with a slow slope like the spectrum SP1 as Figure 13 shown. At this time, the absolute value of the second derivative DIF becomes a relatively small value as a whole as in the example Figure 26 shown.

[0333] On the other hand, in the spectrum SP of a frame where saturation has occurred, it changes with a sharp slope like the spectrum SP3 as Figure 15 shown. At this time, the absolute value of the second derivative DIF becomes a large value at the position where the slope changes sharply as in the example Figure 26 shown. Therefore, by comparing the absolute value of the second derivative DIF with the second threshold TH2, it is possible to determine whether saturation has occurred in the frame to be processed.

[0334] [Effect]

[0335] In the 2-1st embodiment, it is determined whether saturation has occurred based on the change in the slope of the spectrum SP (the absolute value of the second derivative DIF). In Patent Document 1, saturation is determined when the signal strength is equal to or higher than the signal strength "65535" (ADU) of the saturation charge amount based on the summing gate 215. However, in such a method, it is impossible to determine the presence or absence of saturation for the case where the spectrum SP3 as shown in Figure 15 is obtained. In the 2-1st embodiment, it is determined whether the maximum absolute value of the second derivative of the spectrum SP is larger than the second threshold TH2 ( Figure 25 in S505). Thus, even when the spectrum SP3 as shown in Figure 15 is obtained, it is possible to determine the presence or absence of saturation and set the signal strength at saturation (saturation determination value D30) (S507).

[0336] In this way, according to the 2-1st embodiment, instead of determining based on whether it deviates from the Gaussian distribution shape as in the first embodiment, the presence or absence of saturation is determined based on the change in the slope of the spectrum SP (the absolute value of the second derivative DIF). Thus, according to the 2-1st embodiment, in addition to the effects of the 1-1st embodiment, the amount of calculation can also be reduced.

[0337] <Second - 2 Embodiment>

[0338] [Structure of Processing Unit 10]

[0339] The system structure in the second - 2 embodiment is the same as the structure shown except that the saturation determination unit 113 determines the presence or absence of saturation based on the change in the slope of the spectrum SP. Therefore, the illustration of the structure of the processing unit 10 is omitted in the second - 2 embodiment. Figure 21

[0340] [Flowchart]

[0341] Next, with reference to Figure 28 , the processing procedure of the electrophoresis data processing method in the second - 2 embodiment will be described.

[0342] Figure 28 is a flowchart showing the process of the saturation determination process in the second - 2 embodiment. Appropriate reference is made to Figure 21 .

[0343] First, the spectrum generation unit 111 acquires the analysis target sample signal D11 from the measurement unit 20 (S601). Step S601 corresponds to the signal acquisition step.

[0344] Next, the spectrum generation unit 111 depicts (generates) the spectrum SP of the analysis target sample signal D11 frame - by - frame for all frames (refer to Figure 13 ) (S602). Step S602 corresponds to the spectrum generation step.

[0345] Next, the saturation determination unit 113 selects one of the frames. Then, the saturation determination unit 113 determines whether the maximum signal intensity of the spectrum SP depicted in step S602 for the selected frame is equal to or greater than the first threshold TH1 (refer to Figure 13 ) (S603). The first threshold TH1 is the same as the first threshold TH1 used in the first - 1 embodiment.

[0346] In step S603, when the maximum signal intensity of the spectrum SP is equal to or greater than the first threshold TH1 (S603 → Yes), the saturation determination unit 113 calculates the absolute value of the second derivative DIF (refer to Figure 26 ) (S604). The process of step S604 is performed for the frame to be processed.

[0347] Next, the saturation determination unit 113 determines whether the maximum value (maximum absolute value of the second derivative) of the absolute value of the second derivative DIF calculated in step S604 is equal to the second threshold TH2 (refer to Figure 26 ​)Above (S605). The second threshold TH2 is the same as the second threshold TH2 used in the 2-1 embodiment. Step S605 corresponds to a saturation determination step.

[0348] When the absolute value of the maximum second derivative is equal to or greater than the second threshold TH2 (S605 → Yes), the saturation determination unit 113 assigns a saturation mark to the frame to be processed (S606).

[0349] In addition, when the absolute value of the maximum second derivative is less than the second threshold TH2 (S605 → No), the saturation determination unit 113 does not assign a saturation mark to the frame to be processed (S607). That is, in step S607, the saturation determination unit 113 does not perform any processing.

[0350] In step S603, when the maximum signal intensity of the spectrum SP is less than the first threshold TH1 (S603 → No), the saturation determination unit 113 does not assign a saturation mark to the frame to be processed (S607).

[0351] After performing the processes of steps S606 and S607, the saturation determination unit 113 determines whether the processing has been completed for all frames (S610).

[0352] When the processing has not been completed for all frames (S610 → No), the processing unit 10 performs the processing after step S603.

[0353] When the processing has been completed for all frames (S610 → Yes), the saturation determination unit 113 ends the saturation determination process.

[0354] [Operation]

[0355] The case where the spectrum SP depicted in step S602 of Figure 28 is the spectrum SP1 as shown in Figure 13 will be described. In the spectrum SP1 shown in Figure 13 , the maximum signal intensity is equal to or greater than the first threshold TH1 (in the example of Figure 13 it is "20000" (ADU)). Therefore, the saturation determination unit 113 determines "Yes" in step S603 of Figure 28 . Then, in step S604 of Figure 28 , the saturation determination unit 113 calculates the absolute value of the second derivative DIF of the spectrum SP of the frame to be processed.

[0356] Figure 26 is a diagram showing the spectrum SP1 shown in Figure 13 and the absolute value of the second derivative DIF of this spectrum SP1. In Figure 26 , the spectrum SP1 shown by the dashed line is the same as that in Figure 13A spectrum SP that is the same as the spectrum SP1 shown.

[0357] In Figure 26 In the example shown, the maximum value of the second differential absolute value DIF (the maximum second differential absolute value) is less than the second threshold TH2. Therefore, the saturation determination unit 113 determines "no" in Figure 28 step S605 of Figure 28 . That is, the saturation determination unit 113 determines that saturation has not occurred in the frame to be processed. Therefore, the saturation determination unit 113 does not assign a saturation mark to the frame to be processed (

[0358] Next, the case where the spectrum SP depicted in Figure 28 step S602 is the spectrum SP3 as shown in Figure 15 will be described.

[0359] In Figure 15 the spectrum SP3 shown, the maximum signal intensity is equal to or greater than the first threshold TH1 (in the example shown in Figure 15 it is "20000" (ADU)). Therefore, the saturation determination unit 113 determines "yes" in Figure 28 step S603 shown and proceeds to step S604.

[0360] Figure 27 It is a diagram showing Figure 15 the spectrum SP3 shown and the second differential absolute value DIF of the interval B for this spectrum SP3.

[0361] According to Figure 27 the example shown, the maximum value of the second differential absolute value DIF (the maximum second differential absolute value) is equal to or greater than the second threshold TH2. Therefore, the saturation determination unit 113 determines "yes" in Figure 28 step S605 of Figure 28 . That is, the saturation determination unit 113 determines that saturation has occurred in the frame to be processed and assigns a saturation mark to the frame to be processed (

[0362] [Effect]

[0363] In the second - second embodiment, similar to the second - first embodiment, based on the change in the slope of the spectrum SP (the second differential absolute value DIF (refer to Figure 26 )) it is determined whether saturation has occurred ( Figure 28 step S605 of Figure 28S606). In addition, according to the second - second embodiment, similar to the first embodiment, even when using a CCD image sensor 210 with a small saturation charge amount, a saturated mark can be given ( Figure 28 S606).

[0364] According to the second - second embodiment, in addition to the effects of the second - first embodiment, it is possible to determine the presence or absence of saturation without providing the saturation determination value setting unit 112 in the second - first embodiment.

[0365] <Second - third embodiment>

[0366] [Processing unit 10]

[0367] In the second - third embodiment, when setting the saturation determination value D30 by the saturation determination value setting unit 112 in the second - first embodiment, instead of using the analysis object sample D10, a saturation reference sample D40 is used.

[0368] The system structure in the second - third embodiment is the same as Figure 23 except that the saturation determination value setting unit 112 determines the presence or absence of saturation based on the change in the slope of the spectrum SP. Therefore, in the second - third embodiment, the illustration of the processing unit 10 is omitted.

[0369] [Flowchart]

[0370] Next, with reference to Figure 29 , the processing procedure of the electrophoresis data processing method in the second - third embodiment will be described.

[0371] Figure 29 is a flowchart showing the process of the saturation determination value setting process in the second - third embodiment. Appropriate reference is made to Figure 23 .

[0372] First, the spectrum generation unit 111 obtains the saturation reference sample signal D41 from the measurement unit 20 (S701). Step S701 corresponds to the signal acquisition step.

[0373] Next, the spectrum generation unit 111 depicts (generates) the spectrum SP frame - by - frame based on the obtained saturation reference sample signal D41 (S702). Step S702 corresponds to the spectrum generation step.

[0374] Next, the saturation determination value setting unit 112 selects one of the frames. Then, for the selected frame, the saturation determination value setting unit 112 determines whether the maximum signal intensity of the spectrum SP depicted in step S702 is equal to or greater than the first threshold TH1 (refer to Figure 13 ) (S703). The first threshold TH1 is the same as the first threshold TH1 used in the first - first embodiment.

[0375] When the maximum signal intensity of the spectrum SP is less than the first threshold value TH1 (S703 → No), the processing unit 10 moves to the next frame (S709), and the processing unit 10 performs the processing after step S703.

[0376] When the maximum signal intensity of the spectrum SP is equal to or greater than the first threshold value TH1 (S703 → Yes), the saturation determination value setting unit 112 calculates the absolute value of the second derivative DIF for the spectrum SP (see Figure 26 )(S704). The processing of step S704 is performed on the frame to be processed.

[0377] Then, the saturation determination value setting unit 112 determines whether the maximum value (maximum absolute value of the second derivative) of the absolute value of the second derivative DIF calculated in step S704 is equal to or greater than the second threshold value TH2 (see Figure 26 )(S705). The second threshold value TH2 is the same value as the second threshold value TH2 used in the second - 1 embodiment. Step S705 corresponds to the saturation determination step.

[0378] When the maximum absolute value of the second derivative is equal to or greater than the second threshold value TH2 (S705 → Yes), the saturation determination value setting unit 112 determines that saturation has occurred in the measurement unit 20, and performs the processing of step S706. In step S706, the saturation determination value setting unit 112 records the lowest signal intensity in the portion where the signal intensity is substantially constant in the spectrum SP.

[0379] Next, the saturation determination value setting unit 112 sets the recorded signal intensity value as the saturation determination value D30 (S707), and outputs the set saturation determination value D30 to the saturation determination unit 113 (S708).

[0380] When the maximum absolute value of the second derivative is less than the second threshold value TH2 (S705 → No), the saturation determination value setting unit 112 determines whether the frame to be processed is the final frame (S710).

[0381] When the frame to be processed is the final frame (S710 → Yes), the user increases (makes it thicker) the concentration of the saturation reference sample D40. After that, the user performs electrophoresis on the saturation reference sample D40 with the changed concentration again (S712). The reason for performing the processing of steps S711 - S712 is the same as Figure 24 the steps S411 - S412 of

[0382] When the frame to be processed is not the final frame (S710 → No), the processing unit 10 moves to the next frame (S713), and performs the processing after step S703.

[0383] After electrophoresis is performed again in step S712, the processing unit 10 performs the processing below step S701.

[0384] In addition, the processing performed by the saturation determination unit 113 in the second to third embodiments is the same as the processing Figure 12 shown. Therefore, the description of the processing of the saturation determination unit 113 is omitted in the second to third embodiments. However, in the second to third embodiments, after electrophoresis of the analysis target sample D10 is performed again, the processing Figure 12 shown is performed.

[0385] [Function]

[0386] A case where the spectrum SP depicted in step S702 of Figure 29 is the spectrum SP2 as Figure 13 shown will be described. In the spectrum SP2 shown in Figure 13 , the maximum signal intensity is equal to or greater than the first threshold TH1 (in the example shown in Figure 13 it is "20000" (ADU)). Therefore, the saturation determination value setting unit 112 determines "Yes" in step S703 of Figure 29 . Then, the saturation determination value setting unit 112 calculates the absolute value of the second derivative DIF for interval B of the spectrum SP2 of the frame to be processed in step S704 of Figure 29 (see Figure 26 ).

[0387] Figure 26 is a graph showing the spectrum SP1 shown in Figure 13 and the absolute value of the second derivative DIF of the spectrum SP1.

[0388] In the example shown in Figure 26 , the maximum value of the absolute value of the second derivative DIF for interval B (the maximum second derivative absolute value) is less than the second threshold TH2. Therefore, the saturation determination value setting unit 112 determines "No" in step S705 of Figure 29 . That is, the saturation determination value setting unit 112 determines that saturation has not occurred in the frame to be processed. Then, in step S710 of Figure 29 , the saturation determination value setting unit 112 determines whether the frame to be processed is the final frame. If it is the final frame ( Figure 29 S710 → Yes), after the user increases the concentration of the saturation reference sample D40 ( Figure 29 S711), the user performs electrophoresis on the saturation reference sample D40 with the increased concentration again (S712). In addition, if it is not the final frame ( Figure 29 S710 → No), the processing unit 10 proceeds to the next frame (Figure 29 of S713).

[0389] In addition, for the case where the spectrum SP depicted in Figure 29 step S702 is the spectrum SP3 as shown Figure 15 is described. In the spectrum SP3 shown in Figure 15 , the maximum signal intensity is above the first threshold TH1 (in the example shown in Figure 15 , approximately "20000" (ADU)). Therefore, the saturation determination value setting unit 112 determines "yes" in Figure 29 step S703. Then, the saturation determination value setting unit 112 calculates the absolute value of the second derivative DIF for the spectrum SP3 to be processed in Figure 29 step S704 (refer to Figure 26 ).

[0390] Figure 27 is a graph showing Figure 15 the spectrum SP3 shown and the absolute value of the second derivative DIF related to the spectrum SP3.

[0391] In Figure 27 the example shown, the maximum absolute value of the second derivative is above the second threshold TH2. Therefore, the saturation determination value setting unit 112 determines "yes" in Figure 29 step S705. That is, the saturation determination value setting unit 112 determines that saturation has occurred in the frame to be processed. Then, the saturation determination value setting unit 112 records the lowest signal intensity in the portion where the signal intensity is substantially constant in Figure 29 step S706. In Figure 27 the example shown, the portion where the signal intensity is substantially constant is only the top of the spectrum SP. Therefore, in Figure 29 step S706, the saturation determination value setting unit 112 records the signal intensity at the top of the spectrum SP. In Figure 27 the example shown, in Figure 29 step S706, "48000" (ADU) is stored. Then, the saturation determination value setting unit 112 sets the recorded value as the saturation determination value D30 ( Figure 29 of S707). Then, the saturation determination value setting unit 112 outputs the set saturation determination value D30 to the saturation determination unit 113 ( Figure 29 of S708).

[0392] [Effect]

[0393] In the second - third embodiments, as in the second - first embodiment, it is determined whether saturation occurs based on the change in the slope of the spectrum SP (the absolute value of the second derivative DIF (refer to Figure 26 )) ( Figure 29of S705). Thus, as in the first embodiment, the processing unit 10 can determine whether saturation has occurred regardless of the difference in the saturation charge amount between the processing unit 10 and the measurement unit 20. In this way, the saturation determination value setting unit 112 can set the signal intensity at saturation (saturation determination value D30)( Figure 29 of S707). In addition, even when the CCD image sensor 210 with a small saturation charge amount is used, the signal intensity (saturation determination value D30) at the time of saturation can be set (S707).

[0394] According to the second to third embodiments, as in the first to third embodiments, it is possible to set the saturation determination value D30, which is performed each time electrophoresis is performed in the second to first embodiments, by performing electrophoresis of the saturation reference sample D40 only once.

[0395] 《Third Embodiment》

[0396] In the first embodiment, it is determined whether saturation has occurred based on whether the shape of the spectrum SP (refer to Figure 13 ) significantly deviates from the shape of the Gaussian distribution. In addition, in the second embodiment, it is determined whether saturation has occurred based on the change in the slope of the shape of the spectrum SP (absolute value of the second derivative DIF (refer to Figure 26 ). In contrast, in the third embodiment, it is determined whether saturation has occurred based on the sum of the squares of the differences between the spectrum SP of the sample D10 to be analyzed and the spectrum SP of the matrix standard D20.

[0397] <3-1 Embodiment>

[0398] [System Structure]

[0399] Figure 30 is a diagram showing an outline of the structure of the electrophoresis apparatus 1 in the 3-1 embodiment.

[0400] As Figure 30 shown, the electrophoresis apparatus 1 includes a measurement unit 20 and a processing unit 10.

[0401] In addition, the processing unit 10b mainly includes: a fluorescence correction unit 101, a color conversion unit 103, a saturation determination value setting unit 112, and a saturation determination unit 113.

[0402] The processing of the fluorescence correction unit 101 and the color conversion unit 103 has been the same so far.

[0403] The processing performed by the saturation determination unit 113 and the saturation determination unit 113 will be described later.

[0404] In addition, in the 3-1 embodiment, the saturation determination value setting unit 112 has the function of the spectrum generation unit within the scope of the patent claim.

[0405] [Processing unit 10]

[0406] Figure 31 It is a diagram showing in detail the structure of the processing unit 10 in the 3-1st Embodiment.

[0407] As Figure 31 shown, the measurement unit 20 outputs the analysis target sample signal D11 to the processing unit 10. In addition, the measurement unit 20 outputs the matrix standard signal D21 to the processing unit 10.

[0408] The fluorescence correction unit 101 converts the matrix standard signal D21 output from the measurement unit 20 into fluorescence spectrum data D22 of a predetermined shape, and outputs it to the pseudo-inverse matrix generation unit 102 and the saturation determination value setting unit 112.

[0409] The pseudo-inverse matrix generation unit 102 obtains the fluorescence spectrum data D22 output from the fluorescence correction unit 101, and generates a pseudo-inverse matrix D23 of the fluorescence spectrum data D22. The pseudo-inverse matrix generation unit 102 outputs the generated pseudo-inverse matrix D23 to the color conversion unit 103.

[0410] The color conversion unit 103 obtains the analysis target sample signal D11 from the measurement unit 20, and obtains the pseudo-inverse matrix D23 from the pseudo-inverse matrix generation unit 102. Then, the color conversion unit 103 multiplies the analysis target sample signal D11 by the pseudo-inverse matrix D23. Thus, the color conversion unit 103 generates fluorescence signal data D24. Next, the color conversion unit 103 outputs the generated fluorescence signal data D24 to the saturation determination unit 113.

[0411] The frequency spectrum generation unit 111 obtains the analysis target sample signal D11, and outputs the frequency spectrum SP1 of the analysis target sample signal D11.

[0412] The saturation determination value setting unit 112 obtains the normalized analysis target sample signal D11 (normalized analysis target sample signal) from a normalization unit (not shown). In addition, the saturation determination value setting unit 112 obtains the fluorescence spectrum data D22 from the fluorescence correction unit 101. Then, the saturation determination value setting unit 112 sets a saturation determination value D30 based on the normalized analysis target sample signal and the fluorescence spectrum data D22. The saturation determination value setting unit 112 outputs the set saturation determination value D30 to the saturation determination unit 113.

[0413] [Flowchart]

[0414] Next, with reference to Figure 32 , the processing procedure of the electrophoresis data processing method in the 3-1st Embodiment will be described.

[0415] Figure 32It is a flowchart showing the process of saturation determination value setting processing in the 3-1st embodiment. Refer appropriately to Figure 31 .

[0416] First, the spectrum generation unit 111 acquires the sample signal D11 to be analyzed (S801). Step S801 corresponds to the signal acquisition step.

[0417] Next, the saturation determination value setting unit 112 acquires the fluorescence spectrum data D22 from the fluorescence correction unit 101 (S802). In addition, the fluorescence spectrum data D22 is merged. In addition, the fluorescence spectrum data D22 is generated using the matrix standard signal D21 obtained through the merged section B. In steps S801 and S802, the sample signal D11 to be analyzed and the fluorescence spectrum data D22 are acquired for all frames.

[0418] Then, based on the sample signal D11 to be analyzed, the spectrum generation unit 111 depicts (generates) the spectrum SP frame by frame (S803).

[0419] Next, the saturation determination value setting unit 112 selects one of the frames. Then, for the selected frame, the saturation determination value setting unit 112 determines whether the maximum signal intensity of the spectrum SP depicted in step S803 is equal to or greater than the first threshold value TH1 (refer to Figure 13 ). The first threshold value TH1 is the same as the first threshold value TH1 used in the first embodiment.

[0420] When the maximum signal intensity of the spectrum SP is less than the first threshold value TH1 (S804 → NO), the processing unit 10 moves to the next frame (S811), and the processing unit 10 performs the processing after step S804.

[0421] When the maximum signal intensity of the spectrum SP is equal to or greater than the first threshold value TH1 (S804 → YES), the saturation determination value setting unit 112 performs the processing of step S805.

[0422] In step S805, the saturation determination value setting unit 112 normalizes the sample signal D11 to be analyzed for the frame to be processed, and generates a normalized sample signal to be analyzed as the normalized signal intensity. And the spectrum of the normalized sample signal to be analyzed is depicted. In step S805, the saturation determination value setting unit 112 normalizes the sample signal D11 to be analyzed so that the maximum signal intensity in each frame is "1". The normalized sample signal D11 is called the normalized sample signal to be analyzed. Step S805 corresponds to the spectrum generation step.

[0423] Next, the saturation determination value setting unit 112 calculates the sum of squared differences (S806) between the spectrum SP of the standardized analysis target sample signal, which is the spectrum of the standardized signal intensity generated in step S805, and the shape of the fluorescence spectrum data D22 having a predetermined shape. The sum of squared differences is generally calculated as follows. First, the saturation determination value setting unit 112 calculates the difference between the two spectra SP for each interval B. Next, the saturation determination value setting unit 112 squares the calculated difference values respectively. Then, the saturation determination value setting unit 112 sums up the squared difference values respectively. In addition, the fluorescence spectrum data D22 is the spectrum SP of each fluorescence label in the matrix standard signal D21. In step S806, the saturation determination value setting unit 112 compares the shape of the fluorescence spectrum data D22 with the spectrum of the standardized signal intensity (standardized analysis target sample signal) after standardizing the signal intensity.

[0424] In addition, the fluorescence spectrum data D22 includes spectra SP derived from a plurality of matrix standards D20. In step S806, any one of the spectra SP derived from these matrix standards D20 can be used.

[0425] In this way, in step S806, the saturation determination value setting unit 112 calculates the sum of squared differences between the spectrum SP of the standardized analysis target sample signal and the fluorescence spectrum data D22.

[0426] Then, the saturation determination value setting unit 112 determines whether the sum of squared differences calculated in step S806 is equal to or greater than a third threshold value (S807). As the third threshold value, a value that satisfies both of the following (B1) and (B2) is preset in advance. In addition, step S807 corresponds to a saturation determination step.

[0427] (B1) is sufficiently smaller than the sum of squared differences between the spectrum SP of the standardized analysis target sample signal and the fluorescence spectrum data D22 when saturation occurs.

[0428] (B2) is sufficiently larger than the sum of squared differences between the spectrum SP of the standardized analysis target sample signal and the fluorescence spectrum data D22 when saturation does not occur.

[0429] When the sum of squared differences is equal to or greater than the third threshold value (S807 → YES), the saturation determination value setting unit 112 determines that saturation has occurred in the measurement unit 20, and performs the process of step S808. In step S808, the saturation determination value setting unit 112 records the lowest signal intensity in the portion where the signal intensity is substantially constant in the standardized analysis target sample signal. Then, the saturation determination value setting unit 112 sets the signal intensity value recorded in step S808 as the saturation determination value D30 (S809). Then, the saturation determination value setting unit 112 outputs the set saturation determination value D30 to the saturation determination unit 113 (S810).

[0430] When the sum of squares difference is less than the third threshold value in step S807 (S807 → No), the saturation determination value setting unit 112 determines whether the frame to be processed is the final frame (S812). In addition, the frame is a frame in the signal of the analysis target sample signal D11.

[0431] When the frame to be processed is the final frame (S812 → Yes), the saturation determination value setting unit 112 records "65535" (ADU) (S813). Then, the saturation determination value setting unit 112 sets the value of the recorded "65535" (ADU) as the saturation determination value D30 (S809).

[0432] When the frame to be processed is not the final frame (S812 → No), the processing unit 10 moves to the next frame (S814), and the processing unit 10 performs the processing after step S804.

[0433] In addition, the operation of the saturation determination unit 113 in the 3-1st embodiment is the same as Figure 12 Therefore, the illustration and description are omitted.

[0434] [Function]

[0435] For the case where the spectrum SP of the analysis target sample signal D11 depicted in Figure 32 step S803 is the Figure 13 shown spectrum SP1, an explanation is given.

[0436] In Figure 13 the shown spectrum SPSP1, the maximum signal intensity is above the first threshold TH1 (in the Figure 13 shown example, approximately "20000" (ADU) or more). Therefore, the saturation determination value setting unit 112 determines "Yes" in Figure 32 step S804. Then, the saturation determination value setting unit 112 generates a normalized analysis target sample signal for the frame to be processed in Figure 32 step S805. Next, the saturation determination value setting unit 112 calculates the sum of squares difference between the spectrum SP of the generated normalized analysis target sample signal and the fluorescence spectrum data D22 ( Figure 32 S806 of

[0437] In Figure 13 the case of the shown example, the sum of squares difference between the spectrum SP of the normalized analysis target sample signal and the fluorescence spectrum data D22 is smaller than the third threshold value. In addition, the shapes of the spectrum SP of the normalized analysis target sample signal and the spectrum SP of the unnormalized analysis target sample signal D11 are the same except for the height. Therefore, the saturation determination value setting unit 112 inFigure 32 In step S807 of, it is determined as "No". That is, the saturation determination value setting unit 112 determines that saturation has not occurred. After that, the saturation determination value setting unit 112 determines whether the frame is the final frame ( Figure 32 of S812). In the case of the final frame ( Figure 32 of S812 → Yes), the saturation determination value setting unit 112 records "65535" (ADU) ( Figure 32 of S813). In addition, in the case of not the final frame ( Figure 32 of S812 → No), the processing unit 10 proceeds to the next frame ( Figure 32 of S814).

[0438] In addition, the case where the spectrum SP depicted in Figure 32 step S803 of is the Figure 15 spectrum SP3 shown will be described.

[0439] In Figure 15 the spectrum SP3 shown, the maximum signal intensity is the first threshold TH1 (in the Figure 15 example shown is "20000" (ADU) or more. Therefore, the saturation determination value setting unit 112 determines as "Yes" in Figure 32 step S804 of. Then, in Figure 32 step S805 of, the saturation determination value setting unit 112 normalizes the analysis target sample signal D11 to be processed to generate a normalized analysis target sample signal. Next, the saturation determination value setting unit 112 calculates the sum of squared differences between the generated normalized analysis target sample signal and the fluorescence spectrum data D22 ( Figure 32 of S806).

[0440] In Figure 15 this case, the sum of squared differences between the spectrum SP of the normalized analysis target sample signal and the fluorescence spectrum data D22 is above the third threshold. Therefore, the saturation determination value setting unit 112 determines as "Yes" in Figure 32 step S807 of. That is, the saturation determination value setting unit 112 determines that saturation has occurred. After that, the saturation determination value setting unit 112 records the lowest signal intensity in the portion where the signal intensity is substantially constant in Figure 32 step S808 of. In the Figure 15 example shown, the portion where the signal intensity is substantially constant is only the top of the spectrum SP. Therefore, in Figure 32 step S808 of, the saturation determination value setting unit 112 records the signal intensity at the top of the spectrum SP. In the Figure 15 example shown, "48000" (ADU) is recorded. Then, the saturation determination value setting unit 112 sets the recorded value as the saturation determination value D30 ( Figure 32of S809). Then, the saturation determination value setting unit 112 outputs the set saturation determination value D30 to the saturation determination unit 113( Figure 32 of S810).

[0441] The spectrum SP of the normalized analysis target sample signal in the frame where saturation has not occurred is substantially the same as the fluorescence spectrum data D22. Therefore, the sum of the squares of the difference between the spectrum of the normalized analysis target sample signal and the fluorescence spectrum data D22 is approximately "0".

[0442] On the other hand, in the frame where saturation has occurred, as Figure 15 shown in the example, the top of the spectrum SP has a flat shape. In this case, the spectrum SP of the normalized analysis target sample signal becomes a shape that is very different from the fluorescence spectrum data D22. Therefore, the sum of the squares of the difference between the spectrum SP of the normalized analysis target sample signal and the fluorescence spectrum data D22 is a large value. Therefore, the saturation determination value setting unit 112 can determine whether saturation has occurred by comparing the sum of the squares of the difference between the spectrum SP of the normalized analysis target sample signal and the fluorescence spectrum data D22 with the third threshold value.

[0443] [Effect]

[0444] In the 3-1st embodiment, it is determined whether saturation has occurred based on the sum of the squares of the difference between the spectrum SP of the normalized analysis target sample signal and the fluorescence spectrum data D22. In the method of determining saturation when the signal intensity is 65535 (ADU) or more as in Patent Document 1, it is impossible to Figure 15 determine saturation for the spectrum SP3 as shown. In contrast, in the 3-1st embodiment, it is determined whether the sum of the squares of the difference between the spectrum SP of the normalized analysis target sample signal and the fluorescence spectrum data D22 is larger than the third threshold value( Figure 32 of S807). Thus, even for Figure 15 the spectrum SP3 as shown, it is possible to determine that saturation has occurred. And it is possible to set the signal intensity (saturation determination value D30) when saturation occurs (S809).

[0445] According to the 3-1st embodiment, it is determined whether saturation has occurred based on the difference between the shape of the spectrum SP based on the analysis target sample signal D11 and the shape of the spectrum SP based on the matrix standard signal D21. Thus, in the 3-1st embodiment, in addition to the effects of the 1-1st embodiment, it is also possible to accurately determine the presence or absence of saturation.

[0446] <3-2nd Embodiment>

[0447] [System Configuration]

[0448] In the 3-2 embodiment, the saturation determination value setting unit 112 sets the saturation determination value D30. In addition, the saturation determination unit 113 determines the presence or absence of saturation based on whether the analysis target sample signal D11 exceeds the saturation determination value D30. On the other hand, in the 3-2 embodiment, instead of the saturation determination value setting unit 112 setting the saturation determination value D30, the saturation determination unit 113 determines whether saturation has occurred in each frame based on the shape of the spectrum SP.

[0449] [Processing unit 10]

[0450] Figure 33 FIG. is a diagram showing details of the configuration of the processing unit 10 in the 3-2 embodiment.

[0451] Regarding Figure 33 , describe the differences from Figure 31 .

[0452] In Figure 33 , the difference is that the saturation determination value setting unit 112 in Figure 31 is omitted. Other points are the same as Figure 31 , so the description is omitted.

[0453] In addition, in the 3-2 embodiment, the saturation determination unit 113 has the function of the spectrum generation unit within the scope of the claimed invention.

[0454] [Flowchart]

[0455] Next, with reference to Figure 34 , the processing procedure of the electrophoresis data processing method in the 3-2 embodiment will be described.

[0456] Figure 34 FIG. is a flowchart showing the process of determining saturation by the saturation determination unit 113 in the 3-2 embodiment. Appropriate reference is made to Figure 33 .

[0457] First, the saturation determination unit 113 acquires the analysis target sample signal D11 from the measurement unit 20 (S901). Step S901 corresponds to the signal acquisition step.

[0458] Next, the spectrum generation unit 111 acquires the fluorescence spectrum data D22 from the fluorescence correction unit 101 (S902).

[0459] Next, the spectrum generation unit 111 depicts the spectrum SP of the analysis target sample signal D11 frame by frame in all frames (S903). The spectrum SP is the same as before, with the horizontal axis being the interval B number and the vertical axis being the signal intensity of that interval B.

[0460] Next, the saturation determination unit 113 selects one of the frames. Then, for the selected frame, the saturation determination unit 113 determines whether the maximum signal intensity of the spectrum SP depicted in step S903 is equal to or greater than the first threshold TH1 (refer to Figure 13 ).) (S904). The first threshold TH1 is the same as the first threshold TH1 used in the first embodiment.

[0461] In step S904, when the maximum signal intensity of the spectrum SP is equal to or greater than the first threshold TH1 (S904 → Yes), the saturation determination unit 113 performs the process of step S905.

[0462] In step S905, the saturation determination unit 113 generates a standardized analysis target sample signal for the frame to be processed. And the saturation determination unit 113 depicts the spectrum SP of the standardized analysis target sample signal. The standardized analysis target sample signal is generated by the same method as in the third embodiment. Step S905 corresponds to the spectrum generation step.

[0463] Next, the saturation determination unit 113 calculates the sum of squared differences between the spectrum SP of the standardized analysis target sample signal generated in step S905 and the fluorescence spectrum data D22 (S906).

[0464] Next, the saturation determination unit 113 determines whether the sum of squared differences calculated in step S906 is equal to or greater than the third threshold (S907). The third threshold is the same as the third threshold used in the third embodiment. Step S907 corresponds to the saturation determination step.

[0465] When the sum of squared differences is equal to or greater than the third threshold (S907 → Yes), the saturation determination unit 113 assigns a saturation mark to the frame to be processed (S908).

[0466] When the sum of squared differences is less than the third threshold (S907 → No), the saturation determination unit 113 does not assign a saturation mark to the frame to be processed (S909). That is, in step S909, the processing unit 10 does not perform any processing.

[0467] In addition, in step S904, when the maximum signal intensity of the spectrum SP is less than the first threshold TH1 (S904 → No), the saturation determination unit 113 does not assign a saturation mark to this frame (S909).

[0468] After performing the processes of steps S908 and S909, the saturation determination unit 113 determines whether the processing for all frames has been completed (S910).

[0469] When the processing for all frames has not been completed (S910 → No), the processing unit 10 performs the processes after step S904.

[0470] When the processing for all frames is completed (S910 → YES), the saturation determination unit 113 ends the saturation determination process.

[0471] [Function]

[0472] In the 3-2nd Embodiment, similar to the 3-1st Embodiment, the saturation determination unit 113 determines whether saturation has occurred based on the sum of squared differences between the standardized analysis target sample signal and the fluorescence spectrum data D22 (S907). Thus, it is possible to assign a saturation mark to the frames in which saturation has occurred regardless of the difference in the saturation charge amount between devices. Other functions are the same as those in the 1-2nd Embodiment.

[0473] [Effect]

[0474] According to the 3-2nd Embodiment, in addition to the effects obtained in the 3-1st Embodiment, it is also possible to determine the presence or absence of saturation without providing the saturation determination value setting unit 112 in the 3-1st Embodiment.

[0475] <3-3rd Embodiment>

[0476] In the 3-3rd Embodiment, the saturation reference sample signal D41 is used instead of the analysis target sample signal D11 when the saturation determination value setting unit 112 sets the saturation determination value D30 in the 3-1st Embodiment.

[0477] [Processing Unit 10]

[0478] Figure 35 It is a diagram showing the configuration of the processing unit 10 in the 3-3rd Embodiment.

[0479] In Figure 35 it describes the points different from Figure 31 the points different.

[0480] In Figure 35 In the processing unit 10 shown, the spectrum generation unit 111 generates the spectrum SP of the saturation reference sample signal D41 obtained from the saturation reference sample D40. Then, the saturation determination value setting unit 112 calculates the sum of squared differences between the fluorescence spectrum data D22 and the standardized saturation reference sample signal obtained by standardizing the saturation reference sample signal D41. And when the calculated sum of squared differences exceeds the third threshold which is a predetermined threshold, the saturation determination value setting unit sets the saturation determination value D30. Other points are the same as Figure 31 the same. In addition, in Figure 35In the processing unit 10 shown, information related to the analysis target sample signal D11 is not input to the saturation determination value setting unit 112. Further, in the embodiment of step S3-3, the saturation determination value setting unit 112 functions as a spectrum generation unit within the scope of the claimed patent.

[0481] [Flowchart]

[0482] Next, with reference to Figure 36 , the processing procedure of the electrophoresis data processing method in the 3-3 embodiment will be described.

[0483] Figure 36 is a flowchart showing the process of the saturation determination value setting process in the 3-3 embodiment. Appropriate reference is made to Figure 35 .

[0484] First, the spectrum generation unit 111 acquires the saturation reference sample signal D41 from the measurement unit 20 (S1001). Step S1001 corresponds to the signal acquisition step.

[0485] Next, the saturation determination value setting unit 112 acquires the fluorescence spectrum data D22 from the fluorescence correction unit 101 (S1002).

[0486] Next, the spectrum generation unit 111 depicts the spectrum SP of the saturation reference sample signal D41 for each frame of the saturation reference sample signal D41 (S1003). The spectrum SP is configured with the horizontal axis representing the number of the interval B and the vertical axis representing the signal intensity of the interval B, as before.

[0487] Then, the saturation determination value setting unit 112 selects one of the frames. Then, for the selected frame, the saturation determination value setting unit 112 determines whether the maximum signal intensity in the spectrum SP of the saturation reference sample signal D41 depicted in step S1003 is equal to or greater than the first threshold TH1 (refer to Figure 13 ) (S1004). The first threshold TH1 uses the same threshold as the first threshold TH1 used in the 1-1 embodiment.

[0488] If the maximum signal intensity in the spectrum SP is less than the first threshold TH1 (S1004 → No), the processing unit 10 proceeds to the next frame (S1011), and the processing unit 10 performs the processing after step S1004.

[0489] If the maximum signal intensity in the spectrum SP is equal to or greater than the first threshold TH1 (S1004 → Yes), the saturation determination value setting unit 112 performs the processing of step S1005.

[0490] In step S1005, the saturation determination value setting unit 112 normalizes the saturation reference sample signal D41 for the frame to be processed, generating a normalized saturation reference sample signal as the normalized signal intensity. Further, the saturation determination value setting unit 112 depicts the spectrum SP of the normalized saturation reference sample signal. Step S1005 corresponds to the spectrum generation step.

[0491] Next, the saturation determination value setting unit 112 calculates the sum of squared differences between the normalized saturation reference sample signal generated in step S1005 and the fluorescence spectrum data D22 (S1006).

[0492] Next, the saturation determination value setting unit 112 determines whether the sum of squared differences calculated in step S1006 is equal to or greater than a third threshold value (S1007). The third threshold value is the same as the third threshold value used in the 3-1st embodiment. In this way, the saturation determination value setting unit 112 compares the shape of the fluorescence spectrum data D22 with the spectrum of the normalized signal intensity (normalized saturation reference sample signal) after normalizing the signal intensity. Step S1007 corresponds to the saturation determination step.

[0493] When the sum of squared differences is equal to or greater than the third threshold value (S1007 → YES), the saturation determination value setting unit 112 determines that saturation has occurred in the measurement unit 20, and proceeds to the process of step S1008. In step S1008, the saturation determination value setting unit 112 records the signal intensity in the portion where the signal intensity is substantially constant in the spectrum SP of the normalized saturation reference sample signal.

[0494] Next, the saturation determination value setting unit 112 sets the value of the signal intensity recorded in step S1008 as the saturation determination value D30 (S1009), and outputs it to the saturation determination unit 113 (S1010).

[0495] In addition, in step S1007, when the sum of squared differences is smaller than the third threshold value (S1007 → NO), the saturation determination value setting unit 112 determines whether the frame to be processed is the final frame (S1012).

[0496] When the frame to be processed is the final frame (S1012 → YES), the user increases (enriches) the concentration of the saturation reference sample D40 (S1013). Thereafter, the user performs electrophoresis on the saturation reference sample D40 with the changed concentration again (S1014). The reasons for performing the processes of steps S1013 to S1014 are the same as Figure 24 those of steps S411 to S412.

[0497] When the frame to be processed is not the final frame (S1012 → NO), the processing unit 10 advances to the next frame (S1015), and performs the processes after step S1004.

[0498] Again, after electrophoresis is performed again in step S1014, the processing unit 10 performs the processing below step S1001.

[0499] In addition, the processing performed by the saturation determination unit 113 in the 3-3 embodiment is the same as the Figure 12 processing shown, and thus, the illustration and description thereof are omitted. However, in the 3-3 embodiment, after electrophoresis of the analysis target sample D10 is performed again, the Figure 12 processing shown is performed.

[0500] In addition, the processing performed by the saturation determination unit 113 is the same as the Figure 12 above, and thus the illustration and description are omitted.

[0501] [Function]

[0502] In the 3-3 embodiment, similar to the 3-1 embodiment, it is determined whether saturation has occurred (S1007) based on the sum of the squares of the standardized saturation reference sample signal and the fluorescence spectrum data D22. Thereby, it is possible to assign a saturation mark to the frame in which saturation has occurred regardless of the difference in the saturation charge amount between devices. Other functions are the same as those in the 1-3 embodiment.

[0503] [Effect]

[0504] According to the 3-3 embodiment, in addition to the effects obtained in the 3-1 embodiment, the saturation determination value D30 can be roughly determined only by performing electrophoresis on the saturation reference sample D40 once. The reason for achieving such an effect is the same as that in the 1-3 embodiment.

[0505] In the third embodiment, the spectra SP of the analysis target sample signal D11 and the saturation reference sample signal D41 are compared with the fluorescence spectrum data D22 having a predetermined shape. Then, when the shape of the spectrum SP deviates from the fluorescence spectrum data D22 (when the sum of the squares is equal to or greater than the third threshold value), the saturation determination unit 112 and the saturation determination unit 113 determine that saturation has occurred in the measurement unit.

[0506] In the present embodiment, the saturation determination unit 112 and the saturation determination unit 113 determine whether saturation has occurred in the measurement unit 20 based on the shape of the spectrum SP generated by the following method.

[0507] (A1) In the first embodiment, it is determined whether saturation exists based on whether the spectra SP of the analysis target sample signal D11 and the saturation reference sample signal D41 deviate significantly from the Gaussian distribution.

[0508] (Z2)In the second embodiment, it is determined whether the absolute value DIF of the second derivative of the spectra SP of the analysis target sample signal D11 and the saturation reference sample signal D41 is equal to or greater than the second threshold TH2. Thereby, the presence or absence of saturation is determined.

[0509] (Z3)In the third embodiment, the sum of the squared differences of the standardized analysis target sample signal D11, the saturation reference sample signal D41, and the fluorescence spectrum data D22 is calculated. Then, the presence or absence of saturation is determined by determining whether the sum of the squared differences is equal to or greater than a third threshold.

[0510] "Hardware Structure"

[0511] Figure 37 FIG. is a hardware structure diagram showing the processing unit 10.

[0512] The processing unit 10 includes an arithmetic unit 122 composed of a memory 121, a CPU (Central Processing Unit), a GPU (Graphic Processing Unit), etc. Further, the processing unit 10 includes a storage device 123 such as an HD (Hard Disk) or an SSD (Solid State Drive). Further, the processing unit 10 includes an input device 124 such as a keyboard and a mouse, an output device 125 such as a display, and a communication device 126 that obtains information from the measurement unit 20.

[0513] Further, the program stored in the storage device 123 is loaded into the memory 121, and the loaded program is executed by the arithmetic unit 122. Thereby, the fluorescence correction unit 101, the pseudo-inverse matrix generation unit 102, the color conversion unit 103, the spectrum generation unit 111, the saturation determination value setting unit 112, and the saturation determination unit 113 are realized.

[0514] In addition, in the first embodiment, the Gaussian distribution is compared with the spectrum SP of the analysis target sample signal D11. However, instead of the Gaussian distribution, a spectrum having a shape close to the spectrum SP of the analysis target sample signal D11 in which saturation has not occurred may be used. For example, instead of the Gaussian distribution, the spectrum SP of the analysis target sample signal D11 in a case where it is known that saturation has not occurred may be used. Alternatively, instead of the Gaussian distribution, a spectrum obtained by averaging the spectra SP of a large number of analysis target sample signals D11 in cases where it is known that saturation has not occurred may be used.

[0515] The present invention is not limited to the described embodiments and includes various modifications. For example, the described embodiments are embodiments described in detail for easy understanding of the present invention and are not limited to having all the structures described. In addition, a part of the structure of a certain embodiment can be replaced with the structure of another embodiment, and the structure of another embodiment can also be added to the structure of a certain embodiment. In addition, with respect to a part of the structure of each embodiment, addition, deletion, and replacement of other structures can be performed.

[0516] In addition, each of the above-described structures, functions, and units 101 to 103, 111 to 113, the storage device 123, etc. can also be implemented in hardware by, for example, designing a part or all of them using integrated circuits. In addition, as Figure 37 shown, each of the above-described structures, functions, etc. can also be implemented in software by a processor such as a CPU interpreting and executing a program that realizes each function. Information such as programs, tables, and files that realize each function can be stored not only in an HD but also in a memory, a recording device such as an SSD, or a recording medium such as an IC (Integrated Circuit) card, an SD (Secure Digital) card, or a DVD (Digital Versatile Disc).

[0517] In addition, in each embodiment, the control lines and information lines represent the lines considered necessary for explanation, and not all the control lines and information lines are necessarily shown on the product. In fact, it can be considered that almost all the structures are interconnected.

[0518] Symbol Explanation

[0519] 1 Electrophoresis device;

[0520] 10 Processing unit (electrophoresis data processing device);

[0521] 20 Measuring unit;

[0522] 111 Spectrum generation unit;

[0523] 112 Saturation determination value setting unit (saturation determination processing unit);

[0524] 113 Saturation determination unit (saturation determination processing unit);

[0525] 210 CCD image sensor;

[0526] 211 Light receiving unit;

[0527] 211A Light receiving element;

[0528] 212 Integration unit;

[0529] 213 Charge storage unit;

[0530] 213A Charge storage element;

[0531] 214 Horizontal register section;

[0532] 214A Horizontal register;

[0533] 215 Summing gate;

[0534] 220 Control section;

[0535] 240 Capillary array;

[0536] 241 Capillary;

[0537] D10 Analytical object sample;

[0538] D11 Analytical object sample signal;

[0539] D20 Matrix standard;

[0540] D21 Matrix standard signal;

[0541] D22 Fluorescence spectrum data;

[0542] D23 Pseudo-inverse matrix;

[0543] D24 Fluorescence signal data;

[0544] D30 Saturation determination value;

[0545] D40 Saturation reference sample;

[0546] D41 Saturation reference sample signal;

[0547] DIF Second derivative absolute value;

[0548] TH1 First threshold;

[0549] TH2 Second threshold;

[0550] SP, SP1~SP4 Spectra;

[0551] SR1~SR3 Signs;

[0552] S101, S301, S501, S601, S801, S901 Obtain analytical object sample signal (signal acquisition step);

[0553] S102, S302, S402, S502, S602, S702, S803, S903, S1003 Draw spectra by frame (spectrum generation step);

[0554] S104, S304, S404 Determine whether it significantly deviates from the Gaussian distribution (saturation determination step);

[0555] S401, S701, and S1001 obtain a saturation reference sample signal (signal acquisition step);

[0556] S505, S605, and S705 determine whether the absolute value of the maximum second derivative is greater than or equal to a second threshold value (saturation determination step);

[0557] S807, S907, and S1007 determine whether the sum of squared differences is greater than or equal to a third threshold value (saturation determination step).

Claims

1. An electrophoresis data processing device, characterized in that, comprising: a spectrum generation unit that generates a spectrum of a signal obtained from a measurement unit of an electrophoresis apparatus in which light-receiving elements are virtually combined, the light-receiving elements receiving light obtained by splitting fluorescence emitted from a capillary included in the electrophoresis apparatus; and a saturation determination processing unit that determines whether saturation has occurred in the measurement unit based on the shape of the generated spectrum.

2. The electrophoresis data processing apparatus according to claim 1, wherein the saturation determination processing unit compares the shape of the spectrum with a predetermined shape, and determines that saturation has occurred in the measurement unit when the shape of the spectrum deviates from the predetermined shape.

3. The electrophoresis data processing apparatus according to claim 2, wherein the predetermined shape is the shape of a Gaussian distribution.

4. The electrophoresis data processing apparatus according to claim 2, wherein the predetermined shape is the shape of fluorescence spectrum data, and the saturation determination processing unit compares the shape of the fluorescence spectrum data with a spectrum of a normalized signal intensity obtained by normalizing a signal intensity that is the intensity of the signal.

5. The electrophoresis data processing apparatus according to claim 1, wherein the saturation determination processing unit determines that saturation has occurred in the signal obtained from the measurement unit when a value obtained as a result of second-differentiating the shape of the spectrum exceeds a predetermined threshold.

6. The electrophoresis data processing apparatus according to any one of claims 2 to 5, wherein the saturation determination processing unit includes: a saturation determination value setting unit that, when it is determined that saturation has occurred in the measurement unit, sets the lowest signal intensity in a portion of the spectrum where the signal intensity that is the intensity of the signal is substantially constant as a saturation determination value; and a saturation determination unit that, when the signal intensity of a signal obtained from the measurement unit exceeds the saturation determination value, assigns a mark indicating that saturation has occurred in the signal to the obtained signal.

7. The electrophoresis data processing apparatus according to claim 1, wherein when the saturation determination processing unit determines that saturation has occurred in the measurement unit based on the shape of the spectrum, the saturation determination processing unit assigns a mark indicating that saturation has occurred in the signal obtained from the measurement unit to the obtained signal.

8. The electrophoresis data processing apparatus according to claim 1, wherein the spectrum is generated based on a signal intensity obtained as a result of measuring a sample to be analyzed.

9. The electrophoresis data processing apparatus according to claim 2, wherein the spectrum is generated based on a signal intensity obtained as a result of the measurement unit measuring a saturation reference sample.

10. An electrophoresis data processing method, wherein an electrophoresis data processing apparatus processes a signal obtained from a measurement unit of an electrophoresis apparatus in which light-receiving elements are virtually combined, the light-receiving elements receiving light obtained by splitting fluorescence emitted from a capillary included in the electrophoresis apparatus, and the electrophoresis data processing apparatus executes: Signal acquisition step of acquiring the signal from the measurement unit; Spectrum generation step of generating a spectrum of the acquired signal; and Saturation determination step of determining whether saturation has occurred in the measurement unit based on the shape of the generated spectrum.

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