Electrophoresis system, electrophoresis data processing device, and electrophoresis data processing method

Abstract

In order to appropriately compress fluorescence signal data, the present invention is characterized by being provided with: a compression range setting unit (105) for detecting a fluorescence signal caused by an analysis target and a fluorescence signal caused by a non-analysis target, respectively, for fluorescence signals included in the fluorescence signal data; setting a compression range for the frame of the fluorescence signal data according to the detection result; a compression ratio calculation unit (106) that calculates a compression ratio on the basis of the maximum value of the fluorescence signal intensity included in the compression range and the maximum value of the signal intensity that can be used in the secondary analysis; and a compression unit (107) that generates fluorescence signal compressed data by compressing the fluorescence signal data on the basis of the compression ratio, and outputs the generated fluorescence signal compressed data.

Description

Technical Field

[0001] The present invention relates to an electrophoresis system, an electrophoresis data processing device, and an electrophoresis data processing method. Background Art

[0002] Multi-capillary electrophoresis systems are widely used in the analysis of biological samples. These systems fill multiple capillaries with electrophoretic separation media, such as electrolyte solutions, polymer gels, and electrolyte solutions containing polymers, and perform electrophoretic analysis in parallel. Electrophoresis can be used to analyze a wide range of molecules, from low-molecular-weight molecules to high-molecular-weight molecules such as proteins and DNA (deoxyribonucleic acid).

[0003] In particular, in the detection of DNA, a sample with a fluorescent marker attached to the DNA is irradiated with excitation light, and the fluorescent signal emitted by the fluorescent marker is detected. The base sequence and length of the DNA are then analyzed based on the detected fluorescent signal. The fluorescent signal is detected by an image sensor such as a CCD (Charge Coupled Device) image sensor or a CMOS (Complementary Metal Oxide Semiconductor) image sensor. Furthermore, a polycapillary electrophoresis system measures the signal intensity at each wavelength based on the detected fluorescent signal.

[0004] In capillary electrophoresis systems, signal intensity varies depending on sample concentration. Therefore, it is important to improve the detection sensitivity of the image sensor to detect minute signals, while also expanding the dynamic range to detect even strong signals.

[0005] As a means of expanding the dynamic range of image sensors, binning is known, which simulates combining the multiple light-receiving surfaces (corresponding to pixels) that make up the image sensor and treating them as a single pixel. There are two types of binning: hardware binning and software binning. Of these, software binning is more capable of handling higher fluorescence.

[0006] Regarding such binning, Patent Document 1 states that "a fluorescence detection device switches to the software binning to obtain the fluorescence signal intensity when the fluorescence signal intensity obtained by executing the hardware binning exceeds a first threshold value, and switches to the hardware binning to obtain the fluorescence signal intensity when the fluorescence signal intensity obtained by executing the software binning is below the first threshold value." (See Claim 2).

[0007] The polycapillary electrophoresis system also outputs the generated data as a file called a primary analysis file. Secondary analysis is performed by analyzing the base sequence and length of nucleic acids based on the data in the output primary analysis file. Secondary analysis is performed by inputting the primary analysis file output by the polycapillary electrophoresis system into secondary analysis software. This allows for analysis of the base sequence and length of DNA.

[0008] The range of signal intensities that can be input into the secondary analysis software is fixed. On the other hand, the range of signal intensities that can be output by the multi-capillary electrophoresis system is wider than the range of signal intensities that can be input into the secondary analysis software.

[0009] Therefore, fluorescence signal data is generally compressed at a fixed compression rate to converge to a range of values ​​that can be input into the secondary analysis software for the fluorescence signal data output by the multi-capillary electrophoresis system. Non-patent document 1 states that "The CCD detector and computer software in the ABI genetic analyzer use a 2-byte system for data storage, which allows fluorescence values ​​to be encoded using 16 bits (each bit stores a value of 0 or 1). This 2-byte storage format enables the data collection software to provide decimal (base-10) numbers from 0 to 65,535, or binary (base-2) numbers from 0000000000000000 to 1111111111111111. If positive and negative values ​​are allowed, the maximum values ​​of the 2-byte storage system are +32,767 and -32,767."

[0010] Here, in the analysis of a polycapillary electrophoresis system, reagents called primers are used for DNA amplification. Primers are added in excess compared to the target DNA, so the signal intensity caused by the primers is greater than the signal intensity caused by the DNA. Furthermore, the primers are shorter than the target DNA and are therefore detected earlier than the target DNA.

[0011] Furthermore, when software binning is performed, the signal intensity of the primary analysis file can sometimes be significantly greater than the range of signal intensities that can be input into the secondary analysis software due to the influence of the fluorescent signal generated by the primers. To facilitate use in the secondary analysis software, the signal intensities of the primary analysis file are sometimes compressed, but this can result in a high compression ratio in terms of signal intensity, leading to loss of information about DNA with minute signal intensities.

[0012] In addition, as a method for compressing the data size in the time axis direction, there is the selection of data points. Patent Document 2 describes "a method for rejecting clutter, characterized in that the method includes: a step for selecting a first group of data points from a group of data points filtered using an initial threshold reference; a step for selecting a plurality of repeated subgroups of data points from the first group of data points; a step for applying a plurality of linear mappings to the plurality of repeated subgroups of data points; a step for determining a plurality of error values ​​by applying a plurality of linear mappings to the plurality of repeated subgroups of data points; and a step for selecting a first final subgroup of repeated data points having the smallest error value from the first group of data points, the first group of data points having data points in which the repeated data points of the first final subgroup converge within a standardized range, and removing deviating data points." (See Claim 9).

[0013] Prior art literature

[0014] Patent Literature

[0015] Patent Document 1: Japanese Patent Application Laid-Open No. 2015-49179

[0016] Patent Document 2: Japanese Patent Application No. 2003-500662

[0017] Non-patent literature

[0018] Non-patent document 1: John M. Butler, "Advanced Topics in FORENSIC DNA TYPING: INTERPRETATION", p32 Summary of the Invention

[0019] Problems to be solved by the invention

[0020] Patent Document 1 describes a fluorescence detector that performs software binning. However, Patent Document 1 does not describe how to convert the high signal intensity obtained by software binning into a range of values ​​that can be input into secondary analysis software.

[0021] In addition, in non-patent document 1, it is recorded that the signal intensity that can be obtained by the CCD image sensor is "0" to "65,535", which is converted into a value range of "-32,767" to "32,767" by software. However, as mentioned above, when software binning is implemented, the signal intensity that can be obtained increases, so the compression rate in the signal intensity direction becomes larger. As a result, the information of the DNA with a small signal intensity of the analysis object is sometimes lost. Therefore, it is necessary to minimize (optimize) the compression rate in the signal intensity direction. In non-patent document 1, there is no record of the compression method when software binning is implemented.

[0022] Another method for minimizing the compression rate in the signal intensity direction is to select the data points to be analyzed. Patent Document 2 describes a method for reducing data points by removing noise, but does not describe a method for removing fluorescence caused by primers that have increased signal intensity in data output from a polycapillary electrophoresis system.

[0023] In capillary electrophoresis systems, when software binning is performed and the fluorescent signal caused by primers is not removed, the signal intensity increases due to the influence of the primers, resulting in an excessively high compression rate. This high compression rate in the signal intensity direction may result in loss of information about DNA with low signal intensities.

[0024] The present invention has been made in view of the above background, and an object of the present invention is to appropriately compress fluorescence signal data.

[0025] Means for solving problems

[0026] To solve the above-mentioned problems, the present invention comprises: an electrophoresis apparatus; a software binning processing unit that obtains, from the electrophoresis apparatus, an analyte sample signal, which is a signal related to a hardware-binned analyte sample, and a matrix standard signal, which is a signal related to a hardware-binned matrix standard, and performs software binning on the analyte sample signal and the matrix standard signal; a fluorescence signal data generating unit that generates fluorescence signal data, which is data related to fluorescence signal intensity in each frame, based on the software-binned analyte sample signal and the software-binned matrix standard signal; a compression range setting unit that detects, for fluorescence signals included in the fluorescence signal data, a first fluorescence signal caused by the analyte and a second fluorescence signal caused by sources other than the analyte, and sets a compression range for each frame of the fluorescence signal data based on the detection result; a compression ratio calculating unit that calculates a compression ratio based on a maximum value of the fluorescence signal intensities included in the compression range and a maximum value of signal intensities usable in secondary analysis; and a compression unit that compresses the fluorescence signal data based on the compression ratio to generate compressed fluorescence signal data, and outputs the generated compressed fluorescence signal data.

[0027] Other solutions will be described appropriately in the embodiments.

[0028] Effects of the Invention

[0029] According to the present invention, it is possible to perform appropriate compression of fluorescence signal data. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 This is a diagram schematically showing a configuration example of an electrophoresis system according to Embodiment 1-1.

[0031] Figure 2 This is a diagram schematically showing the configuration of a fluorescence detection device in Embodiment 1-1.

[0032] Figure 3 This is a diagram schematically showing the configuration of a CCD image sensor in Embodiment 1-1.

[0033] Figure 4 This is a diagram showing the structure of a processing device according to Embodiment 1-1.

[0034] Figure 5 This is a diagram showing an example of the hardware configuration of a processing device.

[0035] Figure 6 This is a diagram for explaining the operation of converting the spectroscopically separated fluorescence into a digital signal (part 1).

[0036] Figure 7 This is a diagram for explaining the operation of converting the spectroscopically separated fluorescence into a digital signal (part 2).

[0037] Figure 8 This is a diagram for explaining the operation of converting the spectroscopically separated fluorescence into a digital signal (part 3).

[0038] Figure 9 This is a diagram (part 4) for explaining the operation of converting the spectroscopically separated fluorescence into a digital signal.

[0039] Figure 10 This is a diagram (part 5) for explaining the operation of converting the spectroscopic fluorescence into a digital signal.

[0040] Figure 11 This is a diagram showing the timing at which the control device applies pulses.

[0041] Figure 12 This is a diagram showing the generation of a soft bin.

[0042] Figure 13 It is a diagram showing a structural example of a generalized box and a soft box.

[0043] Figure 14 This is a diagram showing an example of the correspondence relationship between soft boxes and boxes.

[0044] Figure 15 This is a flowchart showing the procedure of compression range determination processing performed by the compression range setting unit in the 1-1 embodiment.

[0045] Figure 16 FIG. 1 is a diagram showing an example of an electrophoresis image.

[0046] Figure 17This is a flowchart showing the procedure of compression ratio calculation processing performed by the compression ratio calculation unit in the 1-1 embodiment.

[0047] Figure 18 This is a flowchart showing the steps of compression processing performed by the compression unit in the 1-1 embodiment.

[0048] Figure 19 FIG. 2 is a diagram showing an example of an electrophoresis image.

[0049] Figure 20 FIG. 3 is a diagram showing an example of an electrophoresis image.

[0050] Figure 21 FIG. 4 is a diagram showing an example of an electrophoresis image.

[0051] Figure 22 FIG. 5 is a diagram showing an example of an electrophoresis image.

[0052] Figure 23 FIG. 6 is a diagram showing an example of an electrophoresis image.

[0053] Figure 24 This is a diagram showing the structure of a processing device according to Embodiment 2-1.

[0054] Figure 25 This is a flowchart showing the procedure of compression range determination processing performed by the compression range setting unit in the 2-1st embodiment.

[0055] Figure 26 FIG. 7 is a diagram showing an example of an electrophoresis image.

[0056] Figure 27 FIG. 8 is a diagram showing an example of an electrophoresis image.

[0057] Figure 28 FIG. 9 is a diagram showing an example of an electrophoresis image.

[0058] Figure 29 FIG. 10 is a diagram showing an example of an electrophoresis image.

[0059] Figure 30 FIG. 11 is a diagram showing an example of an electrophoresis image.

[0060] Figure 31 This is a diagram showing an example of a secondary analysis screen displayed in this embodiment. DETAILED DESCRIPTION

[0061] Next, a mode for carrying out the present invention (referred to as “embodiment”) will be described in detail with reference to the drawings as appropriate.

[0062] Hereinafter, embodiments of the present invention will be described in detail based on the accompanying drawings. In addition, in principle, the same reference numerals are given to the same parts in all the drawings for describing the embodiments, and their repeated descriptions are omitted.

[0063] First Implementation Method

[0064] <1-1st embodiment>

[0065] [System Structure]

[0066] Figure 1 This is a diagram schematically showing a configuration example of the electrophoresis system 1 according to the 1-1 embodiment.

[0067] like Figure 1 As shown, the electrophoresis system 1 includes a processing device 10 as an electrophoresis data processing device, an electrophoresis device 20, and an external memory 30. The external memory 30 is a USB (Universal Serial Bus) memory, an external HD (Hard Disk), or the like.

[0068] (Electrophoresis device 20)

[0069] The electrophoresis device 20 is a multicapillary electrophoresis device and includes a pump unit 21 , a high-voltage power supply 22 , a thermostatic chamber 23 , a fluorescence detection device 200 , and a capillary array 240 . The electrophoresis device 20 also includes a sample tray 250 and a transporter 260 .

[0070] The sample tray 250 accommodates a plurality of sample containers 251. Each sample container 251 is a container for storing a sample in which a fluorescent label is added to DNA as a measurement target. Furthermore, each sample container 251 contains a different sample.

[0071] The transporter 260 transports the sample tray 250 so that each sample container 251 is positioned at the tip of the capillary 241 .

[0072] The capillary array 240 is composed of a plurality of capillaries 241. Each capillary 241 is hollow and is inserted into a sample container 251.

[0073] The constant temperature bath 23 maintains the interior of the capillary array 240 at a constant temperature.

[0074] The pump unit 21 injects the electrophoretic medium M (for example, polymer) into each capillary tube 241 , thereby filling the interior of each capillary tube 241 with the electrophoretic medium M.

[0075] The high voltage power supply 22 applies a high voltage to both ends of each capillary 241 filled with the electrophoretic medium M.

[0076] The fluorescence detection position 24 is set on the path of sample electrophoresis. Figure 2 ).

[0077] The sample is electrophoresed by the voltage applied by the high-voltage power supply 22 and moves inside the capillary 241. Figure 1 The moving direction of the sample is indicated by an arrow. The sample moving inside the capillary 241 is irradiated with the excitation light R1 at the fluorescence detection position 24 (see Figure 2 ), emits fluorescence R2 (refer to Figure 2 ). The sample is then discharged into the discharge container 25. Furthermore, the fluorescence detection device 200 detects fluorescence R2 emitted from the sample at the fluorescence detection position 24. The detailed structure of the fluorescence detection device 200 will be described later. By having such a structure in the electrophoresis device 20, it is possible to simultaneously measure samples electrophoresed within the plurality of capillaries 241.

[0078] In this embodiment, a fluorescently labeled DNA fragment is assumed as the sample passing through the interior of the capillary 241 , but a sample other than a DNA fragment may also be used.

[0079] (Processing device 10)

[0080] exist Figure 1 Schematic diagram of the processing device 10 is shown in FIG.

[0081] The processing device 10 includes a signal integration unit 101 as a software binning unit, a fluorescence correction unit 102, a color conversion unit 104, a compression range setting unit 105, a compression rate calculation unit 106, a compression unit 107, etc. The detailed structure of the processing device 10 will be described later.

[0082] (External memory 30)

[0083] The processing performed on the external memory 30 will be described later.

[0084] (Fluorescence Detection Device 200)

[0085] Figure 2 This is a diagram schematically showing the configuration of a fluorescence detection device 200 in the 1-1 embodiment.

[0086] like Figure 2 As shown, the fluorescence detection device 200 includes an excitation light source 201, a shutter 202, and an excitation light lens 203. Furthermore, the fluorescence detection device 200 includes an optical filter 204, a fluorescence lens 205, a diffraction grating 206, and a CCD image sensor 210. Furthermore, the fluorescence detection device 200 includes a control device 220 and a conversion device 230.

[0087] The excitation light source 201 continuously emits the excitation light R1 . The excitation light source 201 is configured to irradiate the excitation light R1 toward all the capillaries 241 in the capillary array 240 passing through the fluorescence detection position 24 .

[0088] The gate 202 repeatedly opens and closes at predetermined intervals. Specifically, when the gate 202 is open, excitation light R1 emitted from the excitation light source 201 irradiates the capillary 241. When the gate 202 is closed, the excitation light R1 is blocked from irradiating the capillary 241. The period from when the gate 202 is closed to when it is opened and then closed again is called a frame.

[0089] The excitation light lens 203 condenses the excitation light R1 that has passed through the gate 202 . The excitation light R1 condensed by the excitation light lens 203 is irradiated toward the fluorescence detection position 24 .

[0090] As described above, the DNA fragments to which the fluorescent labels are attached are used as the samples passing through each capillary 241. The fluorescent labels attached to the DNA fragments electrophoresed in each capillary 241 are excited by irradiation with the excitation light R1 and emit fluorescence R2.

[0091] The optical filter 204 blocks light other than the fluorescent light R2 emitted from the fluorescent marker. As the optical filter 204, for example, a color filter is used.

[0092] The fluorescent lens 205 collects the fluorescent light R2 that has passed through the optical filter 204 .

[0093] The diffraction grating 206 separates the fluorescence R2 focused by the fluorescence lens 205 into wavelengths.

[0094] The CCD image sensor 210 receives the fluorescence R2 separated by the diffraction grating 206 and outputs electric charges corresponding to the intensity of the fluorescence R2.

[0095] The control device 220 instructs the CCD image sensor 210 to output charges based on the fluorescence R2 .

[0096] The conversion device 230 includes a charge conversion unit 231 and a digital conversion unit 232 which is an ADC (Analog digital converter).

[0097] The charge conversion section 231 converts the charge output from the CCD image sensor 210 into a voltage, and outputs the converted voltage as an analog signal.

[0098] The digital converter 232 converts the analog signal output from the charge converter 231 into a digital signal. The digital converter 232 then outputs the converted digital signal to the processing device 10.

[0099] Next, refer to Figure 1 and Figure 2 The measurement of the samples will be described.

[0100] First, the sample is placed 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, so that the sample moves from the sample container 251 into the capillary 241. As a result, the sample moves inside the capillary 241 toward the discharge container 25 via the fluorescence detection position 24 ( Figure 1 Arrow (electrophoresis). During electrophoresis, the sample's migration speed varies depending on the base length of the DNA fragments in the sample. Therefore, DNA fragments with shorter base lengths arrive at fluorescence detection position 24 in descending order. Excitation light R1, emitted from excitation light source 201, passes through gate 202, and is focused by excitation lens 203. The sample that has arrived at fluorescence detection position 24 is irradiated with excitation light R1. The fluorescent labels attached to the DNA fragments are excited by excitation light R1, emitting fluorescence R2. Fluorescence R2 passes through optical filter 204, is focused by fluorescence lens 205, and then dispersed into different wavelengths by diffraction grating 206.

[0101] (CCD image sensor 210)

[0102] Figure 3 1-1 is a diagram showing an overview of the structure of the CCD image sensor 210 in the embodiment. Figure 2 .

[0103] like Figure 3 As shown, the CCD image sensor 210 includes a light receiving portion 211 , a horizontal register portion 212 , and a summing gate 213 .

[0104] The light receiving unit 211 includes a plurality of light receiving elements 211A arranged in a grid pattern. Each light receiving element 211A receives the fluorescence R2 that has been separated by wavelength by the diffraction grating 206. Specifically, the light receiving element 211A receives the fluorescence R2 emitted from the capillary 241 included in the electrophoresis system 1 after being separated by the diffraction grating 206. Upon receiving the fluorescence R2, the light receiving element 211A accumulates a signal charge corresponding to the intensity of the fluorescence R2. Furthermore, the light receiving unit 211 is connected to the control device 220 via a pulse line L1. The signal charge accumulated in each light receiving element 211A constituting the light receiving unit 211 is output based on instructions from the control device 220 via the pulse line L1. Details regarding the output of the signal charge from the light receiving element 211A will be described later.

[0105] The horizontal register section 212 includes multiple horizontal registers 212A. The horizontal registers 212A accumulate signal charges accumulated in the light-receiving element 211A in the vertical direction. In this embodiment, the direction from the light-receiving element 211A toward the horizontal registers 212A is defined as the vertical direction. Furthermore, in this embodiment, the direction from the horizontal register section 212 toward the summing gate 213 is defined as the horizontal direction. The horizontal register section 212 is connected to the control device 220 via a pulse line L2. Each horizontal register 212A constituting the horizontal register section 212 outputs signal charges in response to instructions from the control device 220 via the pulse line L2. Details regarding the output of signal charges from the horizontal registers 212A will be described later.

[0106] The summing gate 213 further accumulates the signal charges accumulated by the horizontal register section 212. The summing gate 213 is connected to the control device 220 via the pulse line L3. The summing gate 213 outputs the accumulated signal charges in response to an instruction from the control device 220 via the pulse line L3.

[0107] In addition, any of the frame transfer type, full frame transfer type, interleaved transfer type, and frame interleaved transfer type can be applied as the CCD image sensor 210. When the frame transfer type, interleaved transfer type, or frame interleaved transfer type is applied, it is not necessary to provide the gate 202 (see Figure 2 ) In addition, when the full-frame transmission type is applied, by increasing the number of light-receiving elements 211A and the area of ​​the light-receiving elements 211A, it is possible to detect a minute signal.

[0108] Alternatively, a CMOS image sensor (Complementary Metal Oxide Semiconductor) may be used for the fluorescent light R2 (see Figure 2 When a CMOS image sensor is used, a digital signal can be directly obtained from each light receiving element 211A.

[0109] [Structure of Processing Device 10]

[0110] Figure 4 This is a diagram showing the structure of the processing device 10 according to the first embodiment. Figure 1 and Figure 2 .

[0111] The processing device 10 includes a signal integration unit 101, a fluorescence correction unit 102, a pseudo-inverse matrix generation unit 103, and a color conversion unit 104. Furthermore, the processing device 10 includes a compression range setting unit 105, a compression ratio calculation unit 106, and a compression unit 107. As described above, the signal integration unit 101 constitutes the software binning processing unit. Furthermore, the fluorescence correction unit 102, the pseudo-inverse matrix generation unit 103, and the color conversion unit 104 constitute the fluorescence signal data generation unit.

[0112] In the electrophoresis system 1, to determine the signal intensity of the sample to be analyzed (hereinafter referred to as the target sample D10), a matrix standard D20 is used separately from the target sample D10. Matrix standard D20 is a sample used for fluorescence calibration. Furthermore, in this embodiment, as described above, the target sample D10 is a mixture of fluorescently labeled DNA fragments and primers. Primers are reagents used for DNA amplification and are added to the target sample D10.

[0113] The electrophoresis device 20 is Figures 6 to 11 The illustrated method outputs a sample signal D11, which is a digital signal (signal) of the sample D10, from the sample D10. The output sample signal D11 is composed of signal intensities associated with each bin B. The output sample signal D11 is input to the signal integration unit 101 of the processing device 10. Furthermore, the sample signal D11 is a signal associated with the sample D10 that has been binned by hardware.

[0114] In addition, the electrophoresis device 20 also measures the matrix standard D20 separately from the analysis target sample D10. Figures 6 to 11 The method shown outputs a matrix standard signal D21, which is a digital signal of the matrix standard D20. The output matrix standard signal D21 consists of the signal intensities associated with each bin B. The output matrix standard signal D21 is input to the signal integration unit 101 of the processing device 10. Furthermore, measurements are performed separately for the analyte sample D10 and the matrix standard D20. Furthermore, the matrix standard signal D21 is a signal associated with the matrix standard D20 binned by hardware.

[0115] In this manner, the signal integrating unit 101 acquires the analyte signal D11 and the matrix standard signal D21 from the electrophoresis apparatus 20 .

[0116] The signal integration unit 101 integrates the input digital signal related to the box B of the analysis target sample D10, that is, the analysis target sample signal D11, for each box B. By this integration, the signal integration unit performs software binning. Software binning will be described later. Figure 3The results of the hardware binning performed by the horizontal register unit 212 and summing gate 213 are further binned. The signal integration unit 101 then outputs the target sample cumulative signal D12 to the color conversion unit 104. This cumulative signal D12 is the result of integrating the target sample signal D11 for each bin B. Furthermore, the signal integration unit 101 integrates the matrix standard signal D21, the digital signal associated with bin B of the matrix standard D20, for each bin B. The signal integration unit 101 then outputs the matrix standard cumulative signal D22 to the fluorescence correction unit 102. This matrix standard cumulative signal D22 is the result of integrating the matrix standard signal D21 for each bin B. In other words, the signal integration unit 101 performs software binning on the matrix standard signal D21.

[0117] In this manner, the signal integration unit 101 performs software binning on the analysis target sample signal D11 and the matrix standard signal D21.

[0118] The fluorescence correction unit 102 normalizes the matrix standard cumulative signal D22 output from the signal integration unit 101 for each frame so that the maximum signal intensity is "1," and outputs the normalized matrix standard cumulative signal D22 to the pseudo-inverse matrix generation unit 103. The normalized matrix standard cumulative signal D22 by the fluorescence correction unit 102 is referred to as fluorescence spectrum data D23.

[0119] Next, upon receiving the fluorescence spectrum data D23 output from the fluorescence correction unit 102 , the pseudo-inverse matrix generation unit 103 generates a pseudo-inverse matrix D24 of the fluorescence spectrum data D23 . The generated pseudo-inverse matrix D24 is output to the color conversion unit 104 .

[0120] Next, the color conversion unit 104 obtains the target sample accumulated signal D12 from the signal accumulation unit 101 and the pseudo-inverse matrix D24 from the pseudo-inverse matrix generator 103. The color conversion unit 104 then multiplies the target sample accumulated signal D12 obtained from the signal accumulation unit 101 by the obtained pseudo-inverse matrix D24. This generates fluorescence signal data D25. The color conversion unit 104 outputs the generated fluorescence signal data D25 to the compression range setting unit 105, the compression rate calculation unit 106, and the compression unit 107.

[0121] The fluorescence correction unit 102, pseudo-inverse matrix generation unit 103, and color conversion unit 104 generate fluorescence signal data D25, which is data regarding the fluorescence signal intensity in each frame. This fluorescence signal data D25 is generated based on the software-binned analyte sample signal D11 and the software-binned matrix standard signal D21.

[0122] When the compression range setting unit 105 obtains the fluorescent signal data D25 from the color conversion unit 104, it generates an electrophoresis image EP (see Figure 16 Then, the compression range setting unit 105 sets the compression range H based on the generated electrophoresis image EP (refer to Figure 20 The method for setting the compression range H will be described later. Then, the compression range setting unit 105 outputs the set compression range H to the compression ratio calculation unit 106 and the compression unit 107.

[0123] The compression ratio calculation unit 106 obtains the compression range H from the compression range setting unit 105 and obtains the fluorescence signal data D25 from the color conversion unit 104. The compression ratio calculation unit 106 then calculates a compression ratio D27 for the fluorescence signal data D25 based on the obtained compression range H and the fluorescence signal data D25. The method for calculating the compression ratio D27 by the compression ratio calculation unit 106 will be described later. The compression ratio calculation unit 106 outputs the calculated compression ratio D27 to the compression unit 107 and the external memory 30, etc.

[0124] The compression unit 107 receives the compression ratio D27 from the compression ratio calculation unit 106, receives the fluorescence signal data D25 from the color conversion unit 104, and receives the compression range H from the compression range setting unit 105. The compression unit 107 then compresses the fluorescence signal data D25 based on the compression range H and the compression ratio D27 to generate compressed fluorescence signal data D28. The method for generating compressed fluorescence signal data D28 will be described later. The compression unit 107 outputs the compressed fluorescence signal data D28 to the external memory 30 or the like.

[0125] [Hardware structure]

[0126] Figure 5 It is a diagram showing a hardware configuration example of the processing device 10 .

[0127] like Figure 5 As shown, the processing device 10 includes a memory 151 , a computing device 152 , a storage device 153 , an input device 154 , an output device 155 , and a communication device 156 .

[0128] The memory 151 is composed of RAM (Random Access Memory) and the like. The computing device 152 is composed of a CPU (Central Processing Unit), a GPU (Graphic Processing Unit), and the like. The storage device 153 is composed of an HD (Hard Disk), an SSD (Solid State Drive), and the like. The input device 154 is composed of a keyboard, buttons, and the like. The output device 155 is composed of a display and the like. Alternatively, the input device 154 and the output device 155 may be integrated using a touch panel display and the like.

[0129] Then, the program stored in the storage device 153 is loaded into the memory 151. Then, the loaded program is executed by the computing device 152. Figure 4 The signal integration unit 101 , the fluorescence correction unit 102 , the pseudo-inverse matrix generation unit 103 , the color conversion unit 104 , the compression range setting unit 105 , the compression rate calculation unit 106 , and the compression unit 107 are shown.

[0130] In addition, the processing device 10 and the electrophoresis device 20 may be an integrated device or may be different devices. In the case where the processing device 10 and the electrophoresis device 20 are an integrated device, Figure 2 The control device 220 and the conversion device 230 shown may also be mounted on the processing device 10 .

[0131] (Hardware Binning)

[0132] Figures 6 to 10 This is used to explain the fluorescence R2 (refer to Figure 2 ) is converted into a digital signal. Figure 2 In addition, Figures 6 to 8 in (and in Figure 3 ), the dotted line shown by the light receiving element 211A represents the box B. The box B will be described later, but the plurality of light receiving elements 211A are collectively regarded as a single light receiving element 211A.

[0133] First, if Figure 2 As shown, the fluorescence R2 separated into each wavelength is received by the light receiving element 211A of the electrophoresis device 20. Figure 6 In this way, the signal charge is accumulated. Figure 6 , the pattern indicated in the light receiving element 211A indicates the signal charge accumulated in each light receiving element 211A.

[0134] The control device 220 applies a pulse to the pulse line L1 for vertically forwarding the signal charge accumulated in each light receiving element 211A. When the pulse is applied to the pulse line L1, the signal charge accumulated in each light receiving element 211A is vertically forwarded to each light receiving element 211A one by one.

[0135] Furthermore, the charge accumulated in the last light receiving element 211A in the vertical direction is transferred to the horizontal register 212A. Figure 6 The accumulated signal charges are forwarded to Figure 7 location.

[0136] Next, the control device 220 applies a pulse to the pulse line L1 again for vertically forwarding the signal charge accumulated in each light receiving element 211A. When the pulse is applied to the pulse line L1, the signal charge accumulated in the light receiving element 211A is forwarded one by one in the vertical direction.

[0137] Furthermore, the signal charge accumulated in the last light receiving element 211A in the vertical direction is transferred to the horizontal register 212A. Thus, the signal charge transferred last time and the signal charge transferred this time are accumulated in each horizontal register 212A. Figure 7 The accumulated signal charges are forwarded to Figure 8 location.

[0138] Then, the control device 220 also applies a pulse to the pulse line L1 for forwarding the signal charge accumulated in each light-receiving element 211A in the vertical direction. When the pulse is applied to the pulse line L1, the signal charge accumulated in each light-receiving element 211A is forwarded to each light-receiving element 211A one by one in the vertical direction.

[0139] Furthermore, the signal charge accumulated in the last light-receiving element 211A in the vertical direction is forwarded to the horizontal register 212A. Thus, the signal charge forwarded the previous time, the signal charge forwarded the previous time, and the signal charge forwarded this time are accumulated in each horizontal register 212A. That is, each time a pulse is applied to the pulse line L1, the signal charge accumulated in the light-receiving element 211A is forwarded to the horizontal register 212A one by one. In the example shown in this embodiment, by applying a total of three pulses to the pulse line L1, the signal charge accumulated in the horizontal register 212A is forwarded to the horizontal register 212A. Figure 9 Signal charges are accumulated as shown.

[0140] Next, the control device 220 applies a pulse to the pulse line L2 for horizontally transferring the signal charge accumulated in the horizontal register 212A. When the pulse is applied to the pulse line L2, the signal charge accumulated in each horizontal register 212A is sequentially transferred horizontally. The timing of applying the pulse to the pulse line L2 will be described later.

[0141] In addition, the signal charge accumulated in the last horizontal register 212A in the horizontal direction is transferred to the summing gate 213. Thus, the signal charge is transferred to Figure 10 Position shown.

[0142] Then, the control device 220 applies a pulse to the summing gate 213 via the pulse line L3, thereby transmitting a pulse from the summing gate 213 to the conversion device 230 (refer to Figure 3 ) output signal charge.

[0143] [Timing of applying pulse]

[0144] Figure 11 1 is a diagram showing the timing at which the control device 220 applies pulses.

[0145] exist Figure 11 , the timing of the pulse applied to the light receiving unit 211, the timing of the pulse applied to the horizontal register unit 212, and the timing of the pulse applied to the summing gate 213 are shown in this order from the upper part of the paper.

[0146] By reference Figures 6 to 10 The operation described above accumulates the signal charges corresponding to the plurality of light-receiving elements 211A in the summing gate 213, thereby being able to be treated as a single light-receiving element 211A in a simulated manner. In this way, treating the plurality of light-receiving elements 211A as a single light-receiving element 211A in a simulated manner is called hardware binning. In addition, the light-receiving elements 211A that are combined in a simulated manner are called bins B (see Figure 3 ).

[0147] exist Figures 6 to 11 In the example shown, a total of three light-receiving elements 211A, three in the vertical direction and one in the horizontal direction, are divided into bins by hardware as one bin B. In each light-receiving element 211A corresponding to bin B, the signal charge is accumulated in the horizontal register 212A and the summing gate 213. Figures 6 to 11 In the example shown, Figure 11 As shown in the example, after applying three pulses to the light receiving unit 211, one pulse is applied to the horizontal register unit 212. After that, one pulse is applied to the summing gate 213. The bin B generated by this hardware binning is Figure 3 In addition, the area where hardware is divided into boxes is not limited to Figures 6 to 11By changing (making it variable) the area of ​​the hardware binning, the sensitivity of the CCD image sensor 210 can be changed. In other words, the size of the bin B is variable. In other words, the size of the bin B can be changed for each electrophoresis.

[0148] And, in Figure 11 In the example shown, three pulses are grouped together for the light receiving unit 211, one pulse is grouped together for the horizontal register unit 212, and one pulse is grouped together for the summing gate 213 (period T). This grouping is repeated multiple times until all the signal charge accumulated in the light receiving unit 211 is transferred to the summing gate 213.

[0149] These operations are performed in synchronization with the timing of gate 202 opening. As described above, the period T from the time gate 202 is closed to the time gate 202 is opened and closed again is called a frame. Furthermore, gate 202 is closed while signal charge is being transferred from light-receiving element 211A to processing device 10. Gate 202 can open when the signal charge accumulated in all light-receiving elements 211A has been transferred to summing gate 213.

[0150] Refer again Figure 3 The signal charge accumulated in the summing gate 213 is converted into a voltage corresponding to the number of signal charges forwarded from the summing gate 213 in the charge conversion section 231. As a result, the charge conversion section 231 outputs the converted voltage as an analog signal to the digital conversion section 232. Figure 11 In the illustrated group (period T), the charge conversion section 231 that finally transfers the signal charge from the summing gate 213 outputs a voltage corresponding to the amount of the transferred signal charge as an analog signal.

[0151] 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 device 10, the external memory 30, etc. In this embodiment, the digital signal is hereinafter referred to as "signal" as appropriate, and the digital signal intensity, which is the intensity of the digital signal, is referred to as "signal intensity" as appropriate.

[0152] In this embodiment, the digital converter 232 is described assuming that the analog signal value when the sum gate 213 is saturated is converted into a digital signal value “65535” (ADU).

[0153] (Software binning)

[0154] Figure 12 It is a diagram showing the generation of the soft box C.

[0155] exist Figure 12shows that soft bin C is generated by accumulating digital signals for each bin B within a frame. The signal accumulation unit 101 accumulates the digital signals associated with the input bin B, allowing multiple bins B to be processed as a single bin B in a simulated manner. This simulated processing of multiple bins B as a single bin B is called software binning. Furthermore, the simulated bins B are called soft bin C. Figure 14 This is a table showing an example of box B constituting soft box C. In addition, the area for software boxing is not limited to Figure 12 as well as Figure 14 By changing the area where the software binning is performed (making it variable), the sensitivity of the CCD image sensor 210 can be changed. In other words, the size of the soft box C is variable.

[0156] exist Figure 12 In FIG, the soft boxes C1 to C20 (C) are generated by performing software binning on 12 of the 240 boxes B1 to B240 (B) output as a result of hardware binning. The value "30000" represented by each box B is the signal strength output by each box B. Figure 12 In the example shown, it is assumed that a signal strength of "30,000" is uniformly output from each box B. Furthermore, the value "360,000" indicated by each soft box C is the signal strength output from each soft box C. In this embodiment, 12 boxes B form one soft box C, so the signal strength output from each soft box C is "30,000 x 12 = 360,000."

[0157] Figure 13 : is a diagram showing an example of the configuration of a generalized box B and a soft box C. Figure 14 This is a diagram showing an example of the correspondence between the soft box C and the box B. Generally, it can be considered that one box B is composed of m light receiving elements 211A in the vertical direction and n light receiving elements 211A in the horizontal direction. Figure 13 The definition of vertical and horizontal directions in Figure 3 Same. That is, in Figure 3 、 Figures 6 to 11 In the example shown, box B is composed of m=3 and n=1. Figure 13 The boxes B1 to BN shown do not overlap with each other. The size of the box B can be changed by changing the timing of applying the pulse by the control device 220.

[0158] In addition, it can be generally considered that the soft box C is composed of k boxes B in the horizontal direction. Figure 12 and Figure 14 In the example shown, the soft box C is composed of k=12. Figure 13 The soft boxes C1 to CL shown do not overlap with each other. Figure 14 In, with Figure 12Likewise, it is shown that soft boxes C1 to C20 (C) are generated by soft binning every 12 boxes of 240 boxes B1 to B240 (B).

[0159] Next, refer to Figures 15 to 18 The following describes the processing steps of the electrophoresis data processing method performed by the compression range setting unit 105, the compression rate calculation unit 106, and the compression unit 107 in the first embodiment. Figure 15 、 Figure 17 、 Figure 18 The above-mentioned treatment may be performed each time electrophoresis is performed, or may be performed collectively after all electrophoresis is completed.

[0160] (Compression range determination processing)

[0161] Figure 15 This is a flowchart showing the steps of the compression range setting process, ie, the compression range determination process, performed by the compression range setting unit 105 in the first embodiment. Figure 16 ] is a diagram showing an example of an electrophoresis image EP. Figure 4 .

[0162] In the compression range determination process, the purpose is to separate the fluorescent signal P originating from the primer from the fluorescent signal P originating from the DNA in order to appropriately compress the fluorescent signal P originating from the DNA.

[0163] First, the compression range setting unit 105 obtains fluorescence signal data D25 from the color conversion unit 104 (S101). In step S101, the compression range setting unit 105 obtains fluorescence signal data D25 for all frames. In subsequent processing similar to step S101, fluorescence signal data D25 for all frames is also obtained. Fluorescence signal data D25 is the result of software binning.

[0164] Next, the compression range setting unit 105 draws (generates) the electrophoresis image EP (see Figure 16 )(S102). The electrophoresis image EP displays the fluorescence signal data D25 as a graph. Figure 16As shown, the compression range setting unit 105 plots a graph with the fluorescence signal data D25 represented by the frame number on the horizontal axis and the fluorescence signal intensity for that frame number on the vertical axis. The frame number is a number assigned to each frame in chronological order from earliest to latest. This graph, with the frame number on the horizontal axis and the fluorescence signal intensity for that frame on the vertical axis, is called an electrophoresis image EP. Furthermore, the electrophoresis image EP is plotted for each electrophoresis. In the electrophoresis image EP, the signal intensity of the fluorescence signal data D25 is constant when the CCD image sensor 210 is not irradiated with fluorescence R. The signal intensity in the fluorescence signal data D25 is referred to as the fluorescence signal intensity. Since the fluorescence signal intensity may become negative due to noise and other factors, a predetermined value is generally added to the calculated fluorescence signal intensity. Therefore, even when the CCD image sensor 210 is not irradiated with fluorescence R, the fluorescence signal intensity generally maintains a predetermined value.

[0165] On the other hand, when the strong fluorescent light R2 is irradiated to the CCD image sensor 210, the signal intensity of the fluorescent signal data D25, that is, the fluorescent signal intensity, becomes stronger. In addition, the fluorescent light R2 is irradiated to the CCD image sensor 210 over a plurality of frames. Therefore, in the electrophoretic image EP, each frame number has a different fluorescent signal intensity. As a result, the electrophoretic image EP is as follows. Figure 16 As shown in FIG. 1 , a plurality of mountain-like shapes are included. The mountain-like shapes are respectively referred to as fluorescent signals P. In addition, as Figure 16 As shown, in this embodiment, the electrophoresis image EP has frame numbers "1" to "5000".

[0166] return Figure 15 Below, refer to Figure 16 .

[0167] Next, the compression range setting unit 105 selects one of the fluorescent signals P included in the generated electrophoresis image EP. At this time, the compression range setting unit 105 searches from the frame number "1" to "5000". Figure 16 The compression range setting unit 105 selects the fluorescence signal intensities corresponding to the frame numbers in this range as one fluorescence signal P.

[0168] Next, the compression range setting unit 105 determines whether the width (frame number) of the selected fluorescent signal P is greater than a first threshold (S103). The first threshold is set to a value that is sufficiently smaller than the width of the fluorescent signal P caused by the primers and sufficiently larger than the width of the fluorescent signal P caused by the target DNA. Because the primers are added in excess relative to the target DNA, the fluorescent signal intensity increases. In other words, the width of the fluorescent signal P caused by the primers is larger than the width of the fluorescent signal P caused by the DNA.

[0169] That is, the width of the fluorescent signal P known to be caused by the primer is set in advance as the first threshold. In this embodiment, "50" frames are set as the first threshold. In addition, the width of the fluorescent signal P is specified by the start frame number and the end frame number of the fluorescent signal P. The start frame number is defined as the first frame number at which the value of the fluorescent signal P is greater than a predetermined value. In addition, the end frame number is the frame number after the start frame number, and is defined as the first frame number at which the value of the fluorescent signal P is less than a predetermined value. However, the value of the first threshold is not limited to "50". The full width at half maximum can also be used as the width of the fluorescent signal P. By using the full width at half maximum, it can be less susceptible to the influence of the baseline.

[0170] If the width of the fluorescent signal P is greater than or equal to the first threshold (S103 → Yes), the compression range setting unit 105 determines whether the area of ​​the fluorescent signal P is greater than or equal to the second threshold (S104). The second threshold is set to a value sufficiently smaller than the area of ​​the fluorescent signal P caused by the primer and sufficiently larger than the area of ​​the fluorescent signal P caused by the target DNA. This is because, for the reasons mentioned above, the area of ​​the fluorescent signal P caused by the primer is larger than the area of ​​the fluorescent signal P caused by the DNA.

[0171] That is, the area of ​​the fluorescent signal P known to be caused by the primer is set in advance as the second threshold value. In this embodiment, "10000000" is set as the second threshold value.

[0172] If the area of ​​the fluorescent signal P is greater than or equal to the second threshold (S104 → Yes), the compression range setting unit 105 determines whether the end frame number of the fluorescent signal P is less than a third threshold (S105). The third threshold is set to a value sufficiently larger than the end frame number of the fluorescent signal P caused by the primer and sufficiently smaller than the end frame number of the fluorescent signal P caused by the target DNA. In other words, the end frame number of the fluorescent signal P known to be caused by the primer is set as the third threshold. This is because the fluorescent signal P caused by the primer is detected before the fluorescent signal P caused by the DNA. In this embodiment, the frame number "2500" is set as the third threshold.

[0173] If the end frame number of the fluorescent signal P is less than the third threshold value (S105→Yes), the compression range setting unit 105 determines that the target fluorescent signal P is a fluorescent signal caused by the primer. Then, the compression range setting unit 105 assigns the target fluorescent signal P a flag JN (see Figure 19 )(S106).

[0174] In addition, in step S103, when the width of the fluorescent signal P is smaller than the first threshold value (S103 → No), the compression range setting unit 105 determines that the target fluorescent signal P is the fluorescent signal P caused by the DNA as the analysis target. Then, the compression range setting unit 105 assigns the analysis target label JY to the target fluorescent signal P (see Figure 19 )(S107).

[0175] In addition, in step S104, when the area of ​​the fluorescent signal P is smaller than the second threshold value (S104→No), the compression range setting unit 105 determines that the target fluorescent signal P is a fluorescent signal P caused by DNA as the analysis target. Then, the compression range setting unit 105 assigns the analysis target label JY to the target fluorescent signal P (see Figure 19 )(S107).

[0176] Similarly, in step S105, when the end frame number of the fluorescent signal P is equal to or greater than the third threshold value (S105 → No), the compression range setting unit 105 determines that the fluorescent signal P is a fluorescent signal P caused by DNA as the analysis target. Then, the compression range setting unit 105 assigns the analysis target label JY to the target fluorescent signal P (see Figure 19 )(S107).

[0177] The fluorescent signal P imparted with the marker JY of the analyte is the first fluorescent signal caused by the analyte. That is, in Embodiment 1-1, the fluorescent signal P caused by the DNA, which is the analyte, is the first fluorescent signal. Furthermore, the fluorescent signal P imparted with the marker JN, which is not the analyte, is the second fluorescent signal caused by something other than the analyte. That is, in Embodiment 1-1, the fluorescent signal P caused by the primer is the second fluorescent signal.

[0178] In this way, the compression range setting unit 105 distinguishes (differentiates and detects) all the fluorescent signals P in the electrophoresis image EP into the fluorescent signals P due to the DNA to be analyzed and the fluorescent signals P due to the primers not to be analyzed.

[0179] After the processing of steps S106 and S107, the compression range setting unit 105 determines whether the processing of all the fluorescent signals P has been completed (S108). For all the fluorescent signals P, whether the processing is completed is determined as follows. That is, the compression range setting unit 105 determines whether the processing of the fluorescent signals P is completed or not until the electrophoresis image EP (see Figure 16 ) whether the fluorescent signal P is detected up to the last frame number of the image.

[0180] If the processing of all the fluorescence signals P has not been completed ( S108 -> No), the compression range setting unit 105 repeats the processing from step S103 onwards.

[0181] When processing is completed for all frames (S108→Yes), the compression range setting unit 105 determines whether a fluorescence signal P outside the analysis target is detected (S109). In other words, in step S109, the compression range setting unit 105 determines whether a fluorescence signal P with a label JN outside the analysis target is detected.

[0182] When a fluorescent signal P outside the analysis object is detected (S109→Yes), the compression range setting unit 105 sets the compression range H (S110). In step S110, the compression range setting unit 105 selects the last (for example, the one with the largest starting frame number) fluorescent signal P among the fluorescent signals P assigned the label JN outside the analysis object. Then, the compression range setting unit 105 obtains the end frame number associated with the selected fluorescent signal P. For example, when the selected fluorescent signal P exists with frame numbers from "1500" to "2000", the compression range setting unit 105 obtains "2000" as the end frame number for the selected fluorescent signal P. Then, the compression range setting unit 105 sets all frame numbers after the next frame number as the compression range H. For example, consider the electrophoresis image EP as Figure 16 The example shown has frame numbers from "1" to "5000." The last frame number associated with the selected fluorescence signal P is "2000." Therefore, the frame number following this frame is "2001." In step S110, the compression range setting unit 105 sets the compression range H from "2001" to "5000" for all frame numbers after "2001." The details of the processing in step S110 will be described later.

[0183] In addition, if the fluorescent signal P to which the marker JN not to be analyzed is assigned is not included in step S109 (S109→No), the compression range setting unit 105 sets all frames to the compression range H (S111). Figure 16 As shown in FIG. 1 , when the electrophoresis image EP has frame numbers from “1” to “5000”, the compression range setting unit 105 sets the range from “1” to “5000” as the compression range H.

[0184] Thus, the compression range setting unit 105 distinguishes and detects the fluorescence signal P caused by the target DNA and the fluorescence signal P caused by the primer from the fluorescence signal included in the fluorescence signal data D25. Then, the compression range setting unit 105 sets the compression range H for the frame of the fluorescence signal data D25 based on the detection result.

[0185] Then, the compression range setting unit 105 outputs the compression range H set in steps S110 and S111 to the compression ratio calculation unit 106 and the compression unit 107 ( S112 ).

[0186] In addition, in Embodiment 1-1, an example was shown in which the first threshold value was set to a constant value of "50," the second threshold value was set to a constant value of "100,000," and the third threshold value was set to a constant value of "2500," but the examples are not limited to these values. The first, second, and third threshold values ​​are appropriately set based on the primers and DNA fragments used in electrophoresis. By appropriately setting the first, second, and third threshold values ​​based on the primers and DNA fragments used in electrophoresis, it is possible to appropriately distinguish between the analyte and the non-analyte, regardless of the electrophoresis conditions.

[0187] In addition, in the first embodiment, Figure 15 In step S103, the width of the fluorescent signal P is determined. In step S104, the area of ​​the fluorescent signal P is determined. In step S105, the timing of detection of the fluorescent signal P is determined. Based on these determinations, the compression range setting unit 105 classifies and determines whether the fluorescent signal P is caused by the analyte (DNA) or the primer. However, this is not limiting, and the fluorescent signal P may be classified and determined based on at least one of the determinations in steps S103 to S105.

[0188] In this manner, the compression range setting unit 105 distinguishes the fluorescence signal P caused by the primer from the fluorescence signal P caused by the analyte DNA, with respect to the fluorescence signal P included in the fluorescence signal data D25. The compression range setting unit 105 performs this detection based on at least one of the width or area of ​​the fluorescence signal P, or the last frame containing the fluorescence signal P (end frame number).

[0189] (Compression ratio calculation process)

[0190] Figure 17 This is a flowchart showing the compression ratio calculation step, that is, the compression ratio calculation process performed by the compression ratio calculation unit 106 in the first embodiment. Figure 4 .

[0191] First, the compression ratio calculation unit 106 obtains the fluorescence signal data D25 from the color conversion unit 104 ( S201 ).

[0192] Next, the compression ratio calculation unit 106 obtains the compression range H from the compression range setting unit 105 ( S202 ).

[0193] Next, the compression ratio calculation unit 106 draws (generates) the electrophoresis image EP (see Figure 16Next, the compression ratio calculation unit 106 obtains the maximum fluorescence signal intensity, or maximum signal intensity D26, which is the maximum fluorescence signal intensity within the fluorescence signal data D25 included in the compression range H (S203). The specific processing of step S203 will be described later. Maximum signal intensity D26 is the maximum fluorescence signal intensity within the fluorescence signal data D25 included in the compression range H. In other words, maximum signal intensity D26 is the maximum fluorescence signal intensity within the compression range H.

[0194] Next, the compression ratio calculation unit 106 calculates the compression ratio D27 based on the maximum signal strength D26 and the upper limit of the value output by the compression unit 107 (S204). The compression ratio D27 calculates the value of the upper limit of the value output by the compression unit 107 / the maximum signal strength D26 as the compression ratio D27. In addition, in this embodiment, the upper limit of the value output by the compression unit 107 is assumed to be "32767" for explanation. The upper limit of the value output by the compression unit 107 is a value determined by secondary analysis. Specifically, the upper limit of the value output by the compression unit 107 is the maximum value (upper limit) of the signal strength that can be used in the secondary analysis. In addition, secondary analysis refers to the analysis of data used by the processing device 10. In addition, the upper limit of the value output by the compression unit 107 is not limited to "32767".

[0195] In this manner, the compression ratio calculation unit 106 calculates the compression ratio D27 based on the maximum signal intensity D26 of the fluorescence signal intensity included in the compression range H and the maximum signal intensity that can be used in the secondary analysis.

[0196] Then, the compression ratio calculation unit 106 outputs the calculated compression ratio D27 to the compression unit 107 and the external memory 30 ( S205 ).

[0197] In addition, about Figure 17 The specific processing content will be described later.

[0198] (Compression processing)

[0199] Figure 18 This is a flowchart showing the compression step, that is, the compression processing step, performed by the compression unit 107 in the first embodiment. Figure 4 .

[0200] First, the compression unit 107 obtains the fluorescence signal data D25 from the color conversion unit 104 ( S301 ).

[0201] Next, the compression unit 107 obtains the compression range H from the compression range setting unit 105 ( S302 ).

[0202] Next, the compression unit 107 obtains the compression ratio D27 from the compression ratio calculation unit 106 ( S303 ).

[0203] The compression unit 107 then selects a frame constituting the acquired fluorescence signal data D25. The compression unit 107 then determines whether the selected frame is included in the compression range H (S304). Frames can be selected in ascending order of frame numbers.

[0204] When the frame is included in the compression range H ( S304 →Yes), the compression unit 107 multiplies the fluorescence signal intensity of the fluorescence signal data D25 corresponding to the frame to be processed by the compression ratio D27 ( S305 ).

[0205] When the selected frame is not included in the compression range H ( S304 →No), the compression unit 107 determines whether the fluorescence signal intensity of the selected frame is greater than “32767” ( S306 ).

[0206] If the fluorescence signal intensity exceeds "32767" (S306 → Yes), the compression unit 107 sets the fluorescence signal intensity of the frame to be processed to "32767" (S307). In other words, if the fluorescence signal intensity in the region outside the compression range H is greater than "32767," the compression unit 107 rounds the fluorescence signal intensity down to "32767" (does not perform compression).

[0207] When the fluorescence signal intensity is equal to or less than "32767" (S306→No), the fluorescence signal intensity of the frame to be processed is set to the original value (S308).

[0208] After performing the processes of steps S305 to S308 , the compression unit 107 determines whether the processes of steps S304 to S308 have been completed for all frames ( S309 ).

[0209] If the processing of steps S304 to S308 has not been completed for all frames (S309→No), the compression unit 107 returns to the processing of step S304. Then, the compression unit 107 performs the processing of steps S304 to S308 on the next frame.

[0210] If steps S304 to S308 have been completed for all frames (S309 → Yes), the compression unit 107 proceeds to step S310. In step S310, the compression unit 107 outputs the fluorescence signal data D25 processed through steps S304 to S308 as compressed fluorescence signal data D28 to the external memory 30 (S310). While the output destination of step S310 is external memory 30 in this embodiment, the compressed fluorescence signal data D28 may also be directly output to a computer performing secondary analysis via a network or the like.

[0211] In this way, the compression unit 107 compresses the fluorescence signal data D25 according to the compression ratio D27 to generate fluorescence signal compressed data D28, and outputs the generated fluorescence signal compressed data D28. Figure 4 As shown, the compression unit 107 outputs the analysis target sample signal D11 and the compression ratio D27 in addition to the fluorescence signal compressed data D28.

[0212] [effect]

[0213] Next, refer to Figures 19 to 21 , explaining the effect of the first embodiment. Figures 19 to 21 , electrophoresis images EP1 and EP2 (EP) of the analysis target sample D10 are shown. The analysis target sample D10 contains a fluorescent signal P due to the analysis target DNA and a fluorescent signal P due to primers other than the analysis target.

[0214] Figures 19 to 21 1 is a diagram showing an example of an electrophoresis image EP.

[0215] In addition, the first threshold is Figure 15 is used in step S103, Figure 19 In the example shown, "50" frames are set as the first threshold. The second threshold is Figure 15 is used in step S104, Figure 19 In the example shown, as described above, "10000000" is set as the second threshold. The third threshold is Figure 15 is used in step S105, Figure 19 In the example shown, as described above, "2500" frames are set as the third threshold.

[0216] (Function of Compression Range Setting Unit 105)

[0217] First, refer to Figure 3 、 Figure 15 、 Figure 19 and Figure 20 The function of the compression range setting unit 105 will be described. In the following description, the step numbers are Figure 15 The step number used in .

[0218] As described above, the compression range setting unit 105 obtains the fluorescence signal data D25 from the color conversion unit 104 (S101). The compression range setting unit 105 draws the Figure 19 The electrophoresis image EP1 (EP) is shown. Figure 19The numerical values ​​shown at the bottom of the graph represent frame numbers. For example, fluorescence signal P1 (P) exists between frame numbers "300" and "800." The same applies to fluorescence signals P2 through P7 (P). Furthermore, frame number "5000" is the last frame number in electrophoresis image EP1 (i.e., fluorescence signal data D25).

[0219] exist Figure 19 In the example, the area of ​​fluorescent signal P1 is "100,000,000," the area of ​​fluorescent signal P2 is "90,000,000," and the area of ​​fluorescent signal P3 is "70,000,000." Furthermore, the area of ​​fluorescent signal P4 is "2,500,000," and the area of ​​fluorescent signal P5 is "1,000,000." Furthermore, the area of ​​fluorescent signal P6 is "3,000,000," and the area of ​​fluorescent signal P7 is "500,000."

[0220] Then, the compression range setting unit 105 starts searching from the frame number “1” among these fluorescent signals P, and processes the fluorescent signal P1 detected first.

[0221] refer to Figure 19 Since the starting frame number of fluorescence signal P1 is "300" and the ending frame number is "800," the frame width of fluorescence signal P1 is "500" frames. Therefore, the frame width of fluorescence signal P1 is greater than the first threshold (50 frames in this embodiment). Therefore, a "yes" determination is made in step S103, and the compression range setting unit 105 proceeds to step S104.

[0222] Next, in step S104, processing is performed based on the area of ​​fluorescence signal P1. As described above, the area of ​​fluorescence signal P1 is "100,000,000." Therefore, fluorescence signal P1 is above the second threshold ("10,000,000" in this embodiment). Therefore, a "yes" determination is made in step S104, and the compression range setting unit 105 proceeds to step S105.

[0223] Next, in step S105, processing is performed based on the ending frame number of the fluorescent signal P1. The ending frame number of the fluorescent signal P1 is "800," which is less than the third threshold ("2500" in this embodiment). As described above, the primer migrates by hand, so it is known up to which point (i.e., the frame number) the primer signal is present. Furthermore, it is known that the primer arrives at the fluorescence detection position 24 before the DNA. Based on this information, the third threshold is pre-set.

[0224] Therefore, if the judgment in step S105 is "yes", the compression range setting unit 105 proceeds to step S106. Figure 19As shown, the compression range setting unit 105 adds a non-analyzed label JN to the fluorescent signal P1 (distinguishing and detecting it as a second fluorescent signal).

[0225] Next, in step S108 , the compression range setting unit 105 determines whether the processing of all the fluorescent signals P has been completed by processing the fluorescent signal P1 . Figure 19 The electrophoresis image EP1 does not include only the fluorescent signal P1 as the fluorescent signal P. Therefore, the determination in step S108 is "No", and the compression range setting unit 105 repeats the processing from step S103 onwards for the fluorescent signal P2.

[0226] Reference Figure 19 , the fluorescence signals P2 and P3 are similar to the fluorescence signal P1, as shown in Figure 19 As shown, in step S106 , a label JN outside the analysis target is assigned (distinguished and detected as a second fluorescent signal).

[0227] After the fluorescence signal P3 is processed to be assigned the non-analyzed flag JN, in step S108, the compression range setting unit 105 determines whether the processing is completed for all the fluorescence signals P. Figure 19 As shown, the fluorescent signals P included in the electrophoresis image EP1 are the fluorescent signals P1 to P3, not all of them. Therefore, the determination in step S108 is "No", and the compression range setting unit 105 repeats the processing from step S103 onwards for the fluorescent signal P4.

[0228] Reference Figure 19 , the start frame number of the fluorescent signal P4 is "2700" and the end frame number is "2720". Therefore, the frame width of the fluorescent signal P4 is "20", which is less than the first threshold ("50" frames in this embodiment). Therefore, the judgment in step S103 is "No", and the compression range setting unit 105 proceeds to step S107. Figure 19 As shown, the label JY of the analysis target is assigned to the fluorescent signal P4 (discriminatively detected as the first fluorescent signal).

[0229] Next, in step S108 , the compression range setting unit 105 determines whether the processing of all the fluorescent signals P included in the electrophoresis image EP1 has been completed by processing the fluorescent signals P1 to P4 . Figure 19 The fluorescence signals P included in the electrophoresis image EP1 are the fluorescence signals P1 to P4, not all of them. Therefore, the determination in step S108 is "No", and the compression range setting unit 105 repeats the processing from step S103 onwards for the fluorescence signal P5.

[0230] Reference Figure 19Similar to the fluorescent signal P4, the fluorescent signals P5 to P7 are assigned the analyte label JY in step S106 (distinguished and detected as the first fluorescent signal).

[0231] Next, in step S108 , the compression range setting unit 105 determines whether the processing of all the fluorescent signals P has been completed by processing the fluorescent signals P1 to P7 . Figure 19 The fluorescent signals P included in the electrophoresis image EP1 are all of the fluorescent signals P1 to P7. Therefore, if the determination in step S108 is "YES", the compression range setting unit 105 proceeds to step S109.

[0232] In step S109, the compression range setting unit 105 determines whether there is a fluorescent signal P to which a marker JN not to be analyzed is assigned. Figure 19 The electrophoresis image EP1 includes fluorescent signals P1 to P3 that are not the subject of analysis. Therefore, if the determination in step S109 is "Yes," the compression range setting unit 105 proceeds to step S110.

[0233] In step S110, the compression range H is determined. Figure 19 As explained above, the fluorescence signal P assigned with the non-analytical marker JN in step S106 is the fluorescence signal P1 to P3. Therefore, the last fluorescence signal P assigned with the non-analytical marker JN is the fluorescence signal P3. Figure 19 As shown in FIG. 1 , the end frame number of the fluorescent signal P3 is “2000” (the frame where the second fluorescent signal is detected). Therefore, the compression range setting unit 105 sets the compression range from the next frame number “2001” (the frame after the frame where the second fluorescent signal is detected) to the next frame number “2000”. Figure 19 The last frame number "5000" in the electrophoresis image EP1 shown is set as the compression range H. Through the above processing, as shown in FIG. Figure 20 The compression range H is determined in this way.

[0234] In this way, the compression range setting unit 105 sets the compression range H starting from the frame after the frame in which the fluorescent signal P due to the primer is detected.

[0235] In addition, in step S110, the compression range setting unit 105 may set the compression range H based on the fluorescence signal P to which the marker JY of the analysis object is assigned. In this case, the initial fluorescence signal P to which the marker JY of the analysis object is assigned becomes the fluorescence signal P4. Figure 19 As shown in FIG. 1 , the starting frame number of the fluorescence signal P4 is “2700”. Therefore, the compression range setting unit 105 sets the compression range from the frame number “2700” to Figure 19 The last frame number “5000” in the electrophoresis image EP1 shown is set as the compression range H.

[0236] The set compression range H is set for the frame of the fluorescent signal data D25 based on the detection results of the fluorescent signals P4 to P7 (first fluorescent signals) caused by the analyte DNA and the fluorescent signals P1 to P3 (second fluorescent signals) caused by the primers.

[0237] Then, in step S112 , the compression range setting unit 105 outputs the set compression range H to the compression ratio calculation unit 106 and the compression unit 107 .

[0238] Thus, the compression range setting unit 105 uses the fluorescence signal P (at Figure 19 In the example shown, the characteristics of fluorescent signals (P1 to P3) are processed. The characteristic of the fluorescent signal P caused by the primer is that it has a wider frame width and a larger area than the fluorescent signal P caused by the target DNA, and is detected at an earlier frame number. This allows the fluorescent signal P caused by the primer to be distinguished from the fluorescent signal P caused by the target DNA, and allows the compression range H to be set.

[0239] (Function of Compression Ratio Calculation Unit 106)

[0240] Next, refer to Figure 4 、 Figure 17 、 Figure 20 , explaining the role of the compression ratio calculation unit 106. In the following statements, the step number is Figure 17 The step number used in .

[0241] The compression ratio calculation unit 106 obtains the fluorescence signal data D25 from the color conversion unit 104 (S201). Next, the compression ratio calculation unit 106 obtains the compression range H from the compression range setting unit 105 (S202). Figure 20 As shown in the example shown in this embodiment, the compression range H is frame numbers "2001" to "5000". Thus, through steps S201 and S202, the compression ratio calculation unit 106 obtains Figure 20 The fluorescence signal data D25 and the compression range H are shown. In step S203, the compression ratio calculation unit 106 obtains the maximum value (maximum signal intensity D26) of the fluorescence signal intensity of the fluorescence signal data D25 included in the compression range H. Figure 20 , the maximum signal intensity D26 of the fluorescence signal intensity in frame numbers "2001" to "5000" is "360000".

[0242] Next, the compression ratio calculation unit 106 calculates the compression ratio D27 in step S204. As described above, the maximum signal strength D26 is "360000," and the upper limit of the value output by the compression unit 107 is "32767." Therefore, the compression ratio calculation unit 106 calculates the compression ratio D27 as "0.091" by dividing (32767 / 360000).

[0243] (Function of the Compression Unit 107)

[0244] Next, refer to Figure 4 、 Figure 18 、 Figure 21 , explaining the function of the compression unit 107. In the following sentences, the step numbers are Figure 18 In addition, in Figure 20 as well as Figure 21 In the figure, "2000" and "2001" written together with the lead lines on the horizontal axis at the bottom of the paper are frame numbers.

[0245] The compression unit 107 obtains the fluorescence signal data D25 from the color conversion unit 104 (S301). Next, the compression unit 107 obtains the compression range H from the compression range setting unit 105 (S302). Figure 20 The fluorescence signal data D25 and the compression range H are shown. Figure 20 As shown, in the example shown in this embodiment, the compression range H is frame numbers "2001" to "5000." Next, the compression unit 107 obtains the compression ratio D27 from the compression ratio calculation unit 106 (S303). As described above, in the example shown in this embodiment, the compression ratio D27 is "0.091." Then, in step S304, the compression unit 107 determines whether the frame to be processed is included in the compression range H.

[0246] For example, refer to Figure 20 Frames corresponding to frame numbers "3800" to "3820" that constitute fluorescence signal P6 are included in compression range H. Therefore, a "yes" determination is made in step S304, and the compression unit 107 proceeds to step S305. In step S305, the compression unit 107 multiplies the fluorescence signal intensity of the target frames by the compression ratio D27. For example, among frame numbers "3800" to "3820," the fluorescence signal intensity of the frame corresponding to the maximum signal intensity D26 is "360,000." Therefore, when the compression unit 107 multiplies the fluorescence signal intensity of this frame by the compression ratio D27, i.e., "0.091," the fluorescence signal intensity of the target frame is compressed to "360,000 × 0.091 = 32,767." The compression unit 107 multiplies the fluorescence signal intensity of each frame included in the compression range H by "0.091."

[0247] On the other hand, the frames corresponding to frame numbers "300" to "800" that constitute the fluorescence signal P1 are not included in the compression range H. Therefore, the determination in step S304 is "No," and the compression unit 107 proceeds to step S306. Then, in step S306, the compression unit 107 determines whether the fluorescence signal intensity of the frame being processed is greater than "32767." For frames with fluorescence signal intensities greater than "32767," the compression unit 107 rounds down the fluorescence signal intensities to "32767" (S307). As described above, no compression is performed in step S307. Furthermore, for frames with fluorescence signal intensities less than "32767," the compression unit 107 sets the fluorescence signal intensities to the original values ​​(S308). The compression unit 107 performs steps S306 to S308 on each frame of the electrophoresis image EP (fluorescent signal data D25) that is outside the compression range H.

[0248] The processing of steps S304 to S308 is performed on each frame constituting the fluorescence signal data D25. Figure 21 The electrophoresis image EP2 shown is equivalent to the fluorescence signal compression data D28. Figure 21 In the figure, the dotted line V1 represents the equivalent Figure 20 The value of the maximum signal intensity D26 (the fluorescence signal intensity of the compressed fluorescence signal P6). Figure 21 As shown, in the compression range H, the fluorescence signal data D25 is compressed so as to be equivalent to Figure 20 The maximum signal intensity D26 value becomes the maximum signal intensity that can be used in the secondary analysis. In this embodiment, the maximum signal intensity that can be used in the secondary analysis is "32676." In other words, the dotted line V1 corresponds to the maximum signal intensity that can be used in the secondary analysis. For regions outside the compression range H, the compression unit 107 performs steps S306 to S308. As a result, the fluorescence signals P shown by the fluorescence signals P1 to P3 have portions above the value "32676" removed.

[0249] [Effect]

[0250] Patent Document 1 describes a method of switching between hardware binning and software binning. However, Patent Document 1 does not describe a means for using the values ​​output by the electrophoresis system 1 in a secondary analysis.

[0251] However, according to the first embodiment, when the value of the fluorescence signal data D25 exceeds the fluorescence signal intensity "32767" that can be used in the secondary analysis, processing is performed to reduce the fluorescence signal intensity to "32767." This allows the fluorescence signal intensity of all frames in the output fluorescence signal compressed data D28 to be reduced to "32767" or less, thus enabling secondary analysis.

[0252] Furthermore, according to the first embodiment, the fluorescence signal data D25 is compressed based on the fluorescence signal P generated by the target DNA. This minimizes the compression ratio D27. Minimizing the compression ratio D27 maintains a small fluorescence signal P. Minimizing the compression ratio D27 means calculating the minimum compression ratio D27.

[0253] Non-Patent Document 1 describes compressing data at a fixed compression ratio D27 so that the values ​​output by the electrophoresis system 1 fall within the range of values ​​that can be input into the secondary analysis software. However, the data output by the electrophoresis system 1 includes the fluorescent signal P of the reagents used for DNA amplification, called primers. As mentioned above, the primers are added in excess compared to the target DNA, resulting in a higher fluorescent signal intensity. Furthermore, the primers are shorter than the target DNA and are therefore detected earlier than the target DNA.

[0254] When software binning is performed, the fluorescence signal intensity obtained by the electrophoresis system 1 significantly exceeds the range of values ​​that can be input into the secondary analysis software due to the influence of the fluorescence signal P caused by the primers. Therefore, when compression is performed at the fixed compression ratio D27 described in Non-Patent Document 1, the compression ratio D27 in the direction of fluorescence signal intensity may increase, reducing the information of DNA with low fluorescence signal intensity to be analyzed.

[0255] The digital converter 232 described in the first embodiment converts the analog signal value when the sum gate 213 is saturated into a digital signal value "65535" (ADU). Then, the signal integration unit 101 Figure 14 Perform software binning. At this time, the maximum value of the fluorescence signal intensity output after software binning is "65535×12=786420". In addition, "12" is based on Figure 14 Box B (see Figure 3 ). If the upper limit of the value that can be input into the secondary analysis software is "32767," the compression ratio D27 becomes "32767 / 786420 = 0.042." In this case, due to the excessively high compression ratio D27, the minute fluorescence signal P due to DNA may not be maintained. In other words, the fluorescence signal P due to DNA becomes too small, making secondary analysis difficult.

[0256] Patent Document 2 describes the selection and processing of data points for experimental data. Data point selection can be understood as the selection of the horizontal axis when graphing experimental data. Furthermore, Patent Document 2 describes the deletion of data points through data point selection and the standardization (processing) of the vertical axis when graphing experimental data.

[0257] Patent Document 2 describes a method for reducing data points by removing noise. However, Patent Document 2 does not describe a method for removing fluorescence caused by primers that have increased signal intensity in data output from the electrophoresis system 1 .

[0258] In contrast, the first embodiment relates to selection of an analysis target range (selection on the horizontal axis) and compression of data on the analysis target range (processing on the vertical axis) based on primers specific to electrophoresis.

[0259] However, according to the 1-1 embodiment, the compression rate D27 can be minimized by distinguishing the fluorescent signal P caused by the primer and the fluorescent signal P caused by the DNA to be analyzed.

[0260] The following describes a comparison between the technology described in Patent Document 2 and the content described in Embodiment 1-1. First, regarding the selection of the horizontal axis, in Patent Document 2, the horizontal axis of the graph related to the experimental data is selected by deleting the data points. In addition, in Patent Document 2, the spectrum of each data point (a graph with the horizontal axis being the wavelength and the vertical axis being the signal intensity) is compared with a specific shape, and the data of the data points that are inconsistent with the specific shape are deleted. In contrast, in Embodiment 1-1, the selection of the horizontal axis is performed by setting the range (compression range H) used for analysis. Specifically, in Embodiment 1-1, the range (compression range H) used for the secondary analysis is determined based on the characteristics of the fluorescent signal generated uniquely by the pretreatment in electrophoresis such as primers.

[0261] Next, regarding the processing related to the vertical axis, in patent document 2, the purpose is to make it easy to observe on the GUI. Moreover, in patent document 2, the processing related to the vertical axis is achieved by standardizing the vertical axis of the graph (not necessarily compressing). In patent document 2, due to the standardization, the information of the signal intensity ratio between the peaks of the signal is lost. In contrast, in the first-1 embodiment, the purpose of the processing related to the vertical axis (compression) is to not lose the information of tiny signals such as the fluorescent signal P caused by DNA, and to converge the value to a range that can be used for secondary analysis. Moreover, in the first-1 embodiment, with respect to the range as the analysis object (compression range H), the signal intensity maximum value D26 is compressed to a value that can be used in the secondary analysis. The fluorescence signal data D25 is uniformly compressed as a whole, so that the information of the fluorescence signal intensity ratio between the peaks of the fluorescence signal P can be maintained. This is because the fluorescence signal intensity ratio is important in the secondary analysis.

[0262] As described above, the technology described in Patent Document 2 is completely different from the content described in Embodiment 1-1.

[0263] In addition to Patent Documents 1 and 2 and Non-Patent Document 1, there are many technologies related to data compression that converge data values ​​to a certain value or less. However, unlike the first embodiment, no technology has yet selected a range (compression range H) for calculating the compression ratio D27 for the horizontal axis of the electrophoresis image EP.

[0264] That is, the fluorescence signal P caused by the primer and the fluorescence signal P caused by the DNA to be analyzed can be distinguished by the compression range setting unit 105. The compression range setting unit 105 sets the compression range H, and the compression ratio calculation unit 106 sets the compression ratio D27 based on the compression range H. In this way, the compression ratio calculation unit 106 can minimize the compression ratio D27. Figure 20 In the electrophoresis image EP1 shown, the fluorescence signal intensities of the primer-induced fluorescence signals P1-P3 are "786420," significantly greater than the fluorescence signal intensities of the DNA-induced fluorescence signals P4-P7. In this case, the compression ratio calculation unit 106 also obtains the maximum signal intensity D26 based on the fluorescence signal P6 of the target DNA and calculates the compression ratio D27 based on this maximum signal intensity D26. This allows for the calculation of an appropriate compression ratio D27. In the example shown in this embodiment, the compression ratio D27 is "0.091," which is lower than the compression ratio D27 of "0.042" in accordance with Non-Patent Document 1. As a result, the fluorescence signals P4-P7 caused by DNA are not excessively reduced in the fluorescence signal compression data D28 used for secondary analysis, facilitating secondary analysis.

[0265] Thus, according to the first embodiment, even when the primers of the target sample D10 are mixed, the compression rate D27 can be minimized based on the characteristics of the fluorescent signal P caused by the DNA being analyzed. While maintaining a small signal such as the fluorescent signal P caused by DNA, the fluorescent signal data D25 can be compressed to a range that can be input into the secondary analysis software.

[0266] Furthermore, the method described in Embodiment 1-1 can be implemented by changing the program of processing device 10. That is, the method described in Embodiment 1-1 can be implemented without changing the hardware structure of electrophoresis device 20 or processing device 10. Therefore, since the method described in Embodiment 1-1 can be implemented without changing the structure of electrophoresis device 20, cost savings can be achieved. Furthermore, according to Embodiment 1-1, appropriate compression of fluorescence signal data D25 can be performed without losing the dynamic range characteristics of hardware binning and software binning.

[0267] Next, refer to Figure 12 、 Figure 20 、 Figure 14 Output to the external memory 30 in the 1-1 embodiment will be described.

[0268] In this embodiment Figure 15 The electrophoresis image EP of the analysis target sample D10 generated in step S102 is set as Figure 19 The electrophoresis image EP1 is shown. In addition, it is assumed that Figure 20 The signal intensity of the fluorescence signal P6 is the maximum value D26 in the frame of the analysis target sample signal D11 in the box B. Figure 12 The software is shown in the box. Figure 20 In the example shown, the frame with the maximum signal strength D26 is the frame number "3810". Figure 14 Implement software binning.

[0269] like Figure 12 As shown, the analyte signal D11 of each bin B is uniformly "30000." Therefore, if software binning is performed, the maximum signal intensity of the analyte cumulative signal D12 of the soft bin C becomes "360000" (30000 x 12).

[0270] In contrast, the compression unit 107 Figure 18 The value of the compressed fluorescence signal data D28 after the processing is "32767".

[0271] Furthermore, the analysis target sample signal D11 , the fluorescence signal compressed data D28 according to the present embodiment, and the compression ratio D27 (“0.091” in the present embodiment) are output to the external memory 30 .

[0272] In addition, the user can compare the value of the analysis target sample signal D11 of a specific frame, the value of the fluorescence signal compression data D28 related to the frame, and the compression ratio D27. The value of the analysis target sample signal D11 of a specific frame is, for example, Figure 12 The value of the fluorescence signal compression data D28 related to this frame is, for example, Figure 12 By comparing these, the user can recognize whether the compression process in the first embodiment has been performed.

[0273] According to the first embodiment, the fluorescence signal intensity of the fluorescence signal data D25 can be brought within a range of values ​​that can be input into the secondary analysis software. In this case, the compression ratio D27 is determined based on the maximum signal intensity D26 of the fluorescence signal P within the compression range H and the upper limit used by the secondary analysis software. This allows the secondary analysis software to appropriately analyze the primary analysis file output by the electrophoresis system 1. The primary analysis file refers to the data output by the processing device 10.

[0274] In the first embodiment, the fluorescence signal P is divided into analysis target and non-analysis target, and only the fluorescence signal P in the analysis target range is compressed. This prevents the compression rate D27 from becoming too high, and the information of the minute fluorescence signal P can be maintained.

[0275] The compression range setting unit 105 detects the type of the fluorescent signal P based on at least one of the width and area of ​​the fluorescent signal P and the last frame (end frame number) containing the fluorescent signal P. The types are the fluorescent signal P caused by the DNA to be analyzed and the fluorescent signal P caused by the primer. This enables the fluorescent signal P caused by the DNA to be analyzed and the fluorescent signal P caused by the primer to be analyzed to be distinguished.

[0276] <1st-2nd embodiment>

[0277] Next, refer to Figure 22 and Figure 23 The first and second embodiments of the present invention will be described.

[0278] Figure 22 and Figure 23 1 is a diagram showing an example of an electrophoresis image EP.

[0279] In the 1-1 embodiment, the method of processing electrophoresis data in the electrophoresis image EP including the fluorescence signal P caused by the primer has been described.

[0280] In contrast, in the first and second embodiments, a method for processing electrophoresis data in an electrophoresis image EP (fluorescence signal data D25) that does not include a primer-induced fluorescence signal P is described. In the first and second embodiments, it is shown that the processing described in the first and first embodiments can also be applied to fluorescence signal data D25 that does not include a primer.

[0281] The system configuration and operation in the 1-2 embodiment are the same as those in the 1-1 embodiment. Therefore, illustration of the system configuration and operation (flowchart) in the 1-2 embodiment is omitted.

[0282] [effect]

[0283] Right Figure 15 The electrophoresis image EP depicted in step S102 is Figure 22 The case of the electrophoresis image EP3 shown in FIG. Figure 22 An electrophoresis image EP3 (EP) of the analysis target sample D10 is shown in . The analysis target sample D10 contains only the fluorescent signal P due to the analysis target DNA, and does not contain the fluorescent signal P due to primers other than the analysis target.

[0284] In addition, the first threshold value, the second threshold value, and the third threshold value are the same as those in the 1-1 embodiment.

[0285] (Function of Compression Range Setting Unit 105)

[0286] Reference Figure 3 、 Figure 15 、 Figure 22 , explaining the function of the compression range setting unit 105. In addition, in the following statements, the step numbers are in Figure 15 The step number used in .

[0287] The compression range setting unit 105 obtains the fluorescence signal data D25 from the color conversion unit 104 (S101). The electrophoresis image EP3 (EP) drawn by the compression range setting unit 105 in step S102 is as follows: Figure 22 As shown. Figure 22 As shown, the electrophoresis image EP3 includes 7 fluorescence signals P (P8 to P14).

[0288] exist Figure 22 In the figure, the numbers written with the lead lines on the horizontal axis at the bottom of the paper are frame numbers. Figure 22The electrophoresis image EP3 shown has a range of frame numbers "0" to "5000." Furthermore, fluorescent signal P8 exists in frame numbers "300" to "320," with an area of ​​"30,000,000." Furthermore, fluorescent signal P9 exists in frame numbers "1100" to "1130," with an area of ​​"2,000,000." Furthermore, fluorescent signal P10 exists in frame numbers "2000" to "2020," with an area of ​​"800,000." Furthermore, fluorescent signal P11 exists in frame numbers "2700" to "2720," with an area of ​​"2,500,000." Next, fluorescent signal P12 exists in frame numbers "3175" to "3200," with an area of ​​"1,000,000." Furthermore, fluorescent signal P13 exists in frame numbers "3800" to "3820," with an area of ​​"3,000,000." Furthermore, the fluorescent signal P14 exists in frame numbers "4300" to "4320" and has an area of ​​"500000".

[0289] Then, the compression range setting unit 105 searches from the frame number “1” among these fluorescent signals P, and processes the fluorescent signal P8 detected first.

[0290] Reference Figure 22 , the starting frame number of the fluorescence signal P8 is "300" and the ending frame number is "320", so the frame width is "20" frames. Therefore, the frame width of the fluorescence signal P8 is less than the first threshold value ("50" frames in this embodiment). Therefore, the judgment in step S103 is "No", and the compression range setting unit 105 proceeds to step S107. In step S107, if Figure 22 As shown, the compression range setting unit 105 assigns the analysis target label JY to the fluorescent signal P8 (distinguishing and detecting it as the first fluorescent signal).

[0291] Next, in step S108 , the compression range setting unit 105 determines whether the processing of all the fluorescent signals P has been completed by processing the fluorescent signal P8 .

[0292] Figure 22 The fluorescence signal P shown in the electrophoresis image EP3 is the fluorescence signal P8, not all of them. Therefore, the determination in step S108 is "No", and the compression range setting unit 105 performs the processing from step S103 on the next fluorescence signal P9.

[0293] Reference Figure 22 The compression range setting unit 105 assigns the analysis target label JY to the fluorescent signals P9 to P14 in step S106 (distinguishing and detecting them as the first fluorescent signals), similarly to the fluorescent signal P8 .

[0294] Next, in step S108 , the compression range setting unit 105 determines whether the processing of all the fluorescent signals P has been completed by processing the fluorescent signal P14 . Figure 22 The electrophoresis image EP3 is all of the fluorescence signals P8 to P14. Therefore, the determination in step S108 is "Yes", and the compression range setting unit 105 proceeds to step S109.

[0295] In step S109 , it is determined whether or not there is a fluorescent signal P outside the analysis target. Figure 22 All the fluorescent signals P included in the electrophoresis image EP3 are fluorescent signals P of the analysis target, and do not include fluorescent signals other than those of the analysis target. Therefore, the determination in step S109 is "No", and the compression range setting unit 105 proceeds to step S111.

[0296] In step S111 , the compression range H is determined. As described above, in the example shown in the first and second embodiments, since the fluorescence signal P outside the analysis target is not included, all frames are set as the compression range H. Therefore, the compression range setting unit 105 sets the frame numbers "1" to "5000" of the electrophoresis image EP3 as the compression range H.

[0297] Subsequently, in step S112 , the compression range setting section 105 outputs the set compression range H to the compression ratio calculation section 106 and the compression section 107 .

[0298] In this way, the compression range setting unit 105 can also set the compression range H for the fluorescence signal data D25 that does not include the fluorescence signal P outside the analysis target caused by the primer.

[0299] (Function of Compression Ratio Calculation Unit 106)

[0300] Next, refer to Figure 4 、 Figure 17 、 Figure 22 , explaining the role of the compression ratio calculation unit 106. In the following description, the step number is Figure 17 The step number used in .

[0301] The compression ratio calculation unit 106 obtains the fluorescence signal data D25 from the color conversion unit 104 (S201). Next, the compression ratio calculation unit 106 obtains the compression range H from the compression range setting unit 105 (S202). Figure 22 As shown in FIG. 1 , frame numbers “1” to “5000” are the compression range H. The compression ratio calculation unit 106 obtains the maximum signal intensity D26 of the fluorescence signal data D25 included in the compression range H in step S203. Figure 22 As shown, the maximum signal intensity value D26 of the fluorescence signal data D25 included in the frame numbers "1" to "5000" is "360000".

[0302] Next, in step S204, the compression ratio calculation unit 106 calculates the compression ratio D27. As described above, the maximum signal strength value D26 is "360000," and the upper limit of the value output by the compression unit 107 is "32767," similar to the first embodiment. Therefore, the compression ratio calculation unit 106 calculates "32767 / 360000 = 0.091" as the compression ratio D27.

[0303] (Function of the Compression Unit 107)

[0304] Next, refer to Figure 3 、 Figure 18 、 Figure 22 as well as Figure 23 , explaining the function of the compression unit 107. In the following statements, the step numbers are in Figure 18 The step number used in .

[0305] The compression unit 107 obtains the fluorescence signal data D25 from the color conversion unit 104 (S301). Next, the compression unit 107 obtains the compression range H from the compression range setting unit 105 (S302). In the first-second embodiment, as described above, frame numbers "1" to "5000" constitute the compression range H. Next, the compression unit 107 obtains the compression ratio D27 from the compression ratio calculation unit 106 (S303). In the first-second embodiment, as described above, the compression ratio D27 is "0.091."

[0306] Then, the compression unit 107 selects frames in ascending order of frame numbers, and determines whether the frame to be processed is included in the compression range H in step S304 .

[0307] Reference Figure 22 , all frames constituting fluorescence signals P8 to P14 are within the compression range H. Therefore, the compression unit 107 determines "yes" in step S304 for any of the fluorescence signals P8 to P14. The compression unit 107 then proceeds to step S305, where it multiplies the fluorescence signal intensity of the target frame by the compression ratio D27 (S305). As a result, the fluorescence signal intensity of the frame corresponding to the maximum signal intensity D26 is compressed to "32767" using "360000 x 0.091."

[0308] Through the processing of step S305, the Figure 23 Then, the compression unit 107 converts the electrophoresis image EP4 (EP) shown in step S310 into Figure 23 The electrophoresis image EP4 shown is output as fluorescence signal compressed data D28. Figure 21 In the figure, the dotted line V2 represents the equivalent Figure 22The value of the maximum signal intensity D26 (fluorescence signal intensity of the fluorescence signal P13). Then, as Figure 23 As shown, the fluorescence signal data D25 is compressed so that Figure 22 The value corresponding to the maximum signal strength D26 is the maximum signal strength that can be used in the secondary analysis ("32676" in this embodiment). That is, the dotted line V2 corresponds to the maximum signal strength that can be used in the secondary analysis.

[0309] In this manner, the processing device 10 can also perform compression processing on the electrophoresis image EP (fluorescent signal data D25 ) that does not include the fluorescent signal P caused by the primer, by the processing described in the 1-1 embodiment.

[0310] [Effect]

[0311] According to the first-second embodiment, in addition to the effects of the first-first embodiment, the same effects as those of the first-first embodiment can be achieved even when the fluorescence signal data D25 does not include a fluorescence signal caused by the primer. Specifically, even when the fluorescence signal data D25 does not include a fluorescence signal P caused by the primer, the compression rate D27 can be minimized to maintain a small signal and compress the data to a value that can be input into the secondary analysis software.

[0312] Second Implementation Method

[0313] Next, refer to Figures 25 to 30 , a second embodiment of the present invention is described.

[0314] In the first embodiment, the characteristics of the fluorescent signal P outside the analysis target caused by the primer are used to distinguish the fluorescent signal P and determine the compression range H. In the second embodiment, the compression range H is determined based on the characteristics of the fluorescent signal P and the characteristics of the size standard.

[0315] <2-1st embodiment>

[0316] [System Structure]

[0317] Figure 24 It is a diagram showing the structure of the processing device 10 according to the 2-1 embodiment.

[0318] exist Figure 24 In the example, the sample D10a to be analyzed is a mixture of DNA, primers, and size standards. Figure 4 In addition, the structure shown in Figure 24 The processing device 10 shown in FIG. 1 is different from the first embodiment in the method of setting the compression range H of the compression range setting unit 105. Figure 4 same.

[0319] The size standard is a sample (DNA) whose base length is known and contains multiple fluorescent signals P. The size standard can be used to know the base length of the analysis object DNA. In addition, the number of fluorescent signals P caused by the size standard is known. Moreover, the size standard is used in combination with the analysis object sample D10a. That is, the analysis object sample D10a in the second embodiment contains the size standard. In addition, the range of the base length of the DNA containing the size standard is set to be wider than the range of the base length of the DNA containing the analysis object. That is, the fluorescent signal P caused by the size standard is detected in a range wider than the fluorescent signal P caused by the analysis object DNA.

[0320] The frame number in which the fluorescent signal P from the size standard is detected is later (detected at a later timing) than the frame number in which the fluorescent signal P from the primer is detected. Furthermore, the size standard uses a dye having a different color from that of the DNA to be analyzed.

[0321] [action]

[0322] Reference Figure 25 , the processing steps of the electrophoresis data processing method in embodiment 2-1 are explained.

[0323] (Compression range H determination process)

[0324] Figure 25 This is a flowchart showing the steps of the compression range setting process, ie, the compression range determination process, performed by the compression range setting unit 105 in the second embodiment. Figure 4 .

[0325] First, the compression range setting unit 105 obtains the fluorescence signal data D25 from the color conversion unit 104 (S401). In step S401, the compression range setting unit 105 obtains the fluorescence signal data D25 for all frames.

[0326] Next, the compression range setting unit 105 draws (generates) the electrophoresis image EP (see Figure 16 )(S402). As in the first embodiment, an electrophoresis image EP is generated for each electrophoresis.

[0327] Next, the compression range setting unit 105 selects one of the fluorescent signals P contained in the generated electrophoresis image EP. The method of selecting the fluorescent signal P is the same as that in the first embodiment. Then, the compression range setting unit 105 determines whether the color of the selected fluorescent signal P is the color used in the size standard (the color of the size standard) (S403). The color of the size standard refers to the color of the pigment used in the size standard. As described above, different colors of pigments are used in the size standard and the analysis object DNA. Therefore, the compression range setting unit 105 can distinguish the fluorescent signal P caused by the size standard and the fluorescent signal P caused by the analysis object DNA by color.

[0328] Whether the color is that of the size standard is determined based on the color information in the fluorescent signal P.

[0329] When the fluorescent signal P is not the color of the size standard ( S403 → No), the compression range setting unit 105 selects the next fluorescent signal P ( S404 ) and performs the processing after step S403 .

[0330] If the fluorescent signal P is the color of the size standard (S403→Yes), the compression range setting unit 105 adds the size standard mark JS ( Figure 26 )(S405). That is, the compression range setting unit 105 adds a flag JS to the fluorescent signal P determined to be the fluorescent signal P caused by the size standard.

[0331] The fluorescent signal P that is not assigned the mark JS of the size standard means the fluorescent signal P that is detected as being caused by the DNA to be analyzed. The fluorescent signal P that is not assigned the mark JS of the size standard is the first fluorescent signal caused by the DNA to be analyzed. That is, in the 2-1 embodiment, the fluorescent signal P caused by the DNA to be analyzed is the first fluorescent signal. In addition, the fluorescent signal P that is assigned the mark JS of the size standard means the fluorescent signal P that is detected as being caused by the size standard. The fluorescent signal P that is assigned the mark JS of the size standard is the second fluorescent signal caused by something other than the analysis object. That is, in the 2-1 embodiment, the fluorescent signal P caused by the size standard is the second fluorescent signal. In this way, the compression range setting unit 105 detects the fluorescent signal P caused by the size standard as the second fluorescent signal.

[0332] As described above, in the 2-1st embodiment, the compression range setting unit 105 detects the fluorescent signal P caused by the DNA to be analyzed and the fluorescent signal P caused by the size standard based on the color information of the fluorescent signal P.

[0333] Next, the compression range setting unit 105 determines whether or not all the fluorescent signals P in the electrophoresis image EP have been processed ( S406 ).

[0334] If the processing has not been completed for all the fluorescent signals P ( S406 →No), the compression range setting unit 105 selects the next fluorescent signal P ( S407 ) and performs the processing from step S403 onwards.

[0335] When processing has been completed for all fluorescence signals P (S406 → Yes), the compression range setting unit 105 assigns numbers to the fluorescence signals P assigned the size standard mark JS (S408). At this time, the compression range setting unit 105 assigns numbers starting from "1" to the fluorescence signals P assigned the size standard mark JS in descending order of frame numbers.

[0336] Next, the compression range setting unit 105 determines whether the maximum number of numbers assigned in step S408 is the same as the number of dimension standard products specified (maximum number of numbers = predetermined number: S409). In other words, the compression range setting unit 105 determines whether the maximum number of numbers assigned in step S408 exceeds the number of dimension standard products specified.

[0337] When the maximum value of the assigned numbers is the same as the number of dimensionally standardized products ( S409 →Yes), the compression range setting unit 105 proceeds to step S410 .

[0338] If the maximum value of the assigned numbers differs from the specified number of size standards (S409 → No), the compression range setting unit 105 deletes the size standard marker JS (S411). In this case, the compression range setting unit 105 deletes the size standard marker JS for the fluorescence signals P assigned numbers greater than the specified number. The compression range setting unit 105 then proceeds to step S410. Furthermore, the number of fluorescence signals P assigned the size standard marker JS will not fall below the specified number of size standards.

[0339] In step S410, the compression range setting unit 105 sets the compression range H. In step S410, the compression range setting unit 105 obtains the starting frame number of the fluorescence signal P with the smallest frame number among the fluorescence signals P of the size standard marked with the marker JS. This starting frame number is referred to as the minimum frame number. The compression range setting unit 105 then obtains the ending frame number of the fluorescence signal P with the largest frame number among the fluorescence signals P of the size standard marked with the marker JS. This ending frame number is referred to as the maximum frame number. The compression range setting unit 105 sets the range from the minimum frame number to the maximum frame number as the compression range H.

[0340] As described above, in the 2-1st embodiment, the frame range for detecting the fluorescent signal P (second fluorescent signal) to which the mark JS of the size standard is attached is set as the compression range H.

[0341] Then, the compression range setting unit 105 outputs the compression range H set in step S410 to the compression ratio calculation unit 106 and the compression unit 107 ( S412 ).

[0342] In addition, regarding Figure 25 A specific example of the processing shown will be described later.

[0343] (Compression Ratio Calculation Processing and Compression Processing)

[0344] In the second embodiment, the compression ratio calculation process performed by the compression ratio calculation unit 106 is as follows: Figure 17 The processing shown in FIG2-1 is the same, so the illustration and description of the embodiment 2-1 are omitted. In addition, the steps of the compression processing performed by the compression unit 107 in the embodiment 2-1 are the same as those in FIG2-1. Figure 18 The processing shown is the same, so the description in the 2-1 embodiment is omitted.

[0345] Furthermore, in the compression process of Embodiment 2-1, the fluorescent signal P from the size standard differs from the fluorescent signal P from the primer and does not need to be compressed. This is because the fluorescent signal P from the size standard is smaller than the fluorescent signal P from DNA. In other words, if there is a concern about the amount of fluorescent signal P from the size standard that will be applied to the analyte D10a, the signal can be kept within the range of values ​​output by the compression unit 107 even without compression.

[0346] If the fluorescent signal P caused by the size standard is compressed, the fluorescent signal intensity of the fluorescent signal P caused by the size standard decreases. In this case, the user may not be able to recognize the fluorescent signal P caused by the size standard. As a result, the user may mistakenly believe that the size standard is not included.

[0347] When the fluorescent signal P of the size standard is not compressed, the fluorescent signal intensity of the fluorescent signal P caused by the size standard does not decrease. Therefore, the user does not mistakenly believe that the size standard is not included.

[0348] [effect]

[0349] Next, refer to Figure 18 、 Figures 25 to 28 , explaining the function of the 2-1 implementation method.

[0350] Figures 26 to 28 1 is a diagram showing an example of an electrophoresis image EP.

[0351] In addition, Figures 26 to 28, electrophoresis images EP5 and EP6 (EP) of the sample D10a to be analyzed are shown. In the second embodiment (embodiment 2-1 and embodiment 2-2), the fluorescence signal P caused by the size standard is composed of four fluorescence signals P. In addition, the fluorescence signal P caused by the size standard is not limited to being composed of four fluorescence signals P. In addition, as Figures 26 to 28 As shown, in the electrophoresis image EP, the fluorescent signal P having the color of the size standard is displayed by a single-dot chain line.

[0352] In the second-first embodiment, Figure 26 The electrophoresis image EP5 shown includes fluorescence signals P (P18, P20, P22) caused by the DNA to be analyzed. In addition, the electrophoresis image EP5 includes fluorescence signals P (P15, P16) caused by primers other than the analysis object and fluorescence signals P (P17, P19, P21, P23) caused by size standards. Figure 25 The electrophoresis image EP generated in step S402 is Figure 26 The case of the electrophoresis image EP5 shown will be described.

[0353] (Function of Compression Range Setting Unit 105)

[0354] Reference Figures 25 to 27 , explaining the function of the compression range setting unit 105. In addition, in the following statements, the step numbers are in Figure 25 The step number used in .

[0355] First, the compression range setting unit 105 acquires the fluorescence signal data D25 from the color conversion unit 104 ( S401 ). Figure 26 The electrophoresis image EP5 generated by the compression range setting unit 105 in step S402 is shown. The compression range setting unit 105 then selects one of the fluorescence signals P included in the generated electrophoresis image EP. Specifically, the compression range setting unit 105 searches from frame number "1" among the fluorescence signals P and processes the first detected fluorescence signal P15. The compression range setting unit 105 then determines whether the color of the selected fluorescence signal P is the color used in the size standard (the color of the size standard) (S403).

[0356] Reference Figure 26 The initially selected fluorescent signal P15 is not the color of the size standard. Therefore, the determination in step S403 is "No." Then, the compression range setting unit 105 selects the next fluorescent signal P16 in step S404 (S404) and performs the processing from step S403 onwards.

[0357] Reference Figure 26, the next fluorescent signal P16 of the fluorescent signal P15 is the color of the size standard. Therefore, if the judgment in step S403 is "yes", the compression range setting unit 105 will be as follows Figure 26 As shown, the fluorescent signal P16 is assigned the size standard marker JS (S405). As mentioned above, the fluorescent signal P16 is the fluorescent signal P caused by the primer. However, the color of the fluorescent signal P16 is the same as that of the size standard, so it is mistakenly identified as the fluorescent signal P caused by the size standard. Correction of this misidentification will be described later.

[0358] Next, in step S406 , by processing the fluorescent signal P16 , it is determined whether the processing of all the fluorescent signals P has been completed. Figure 26 The electrophoresis image EP5 is composed of the fluorescence signals P15 and P16, not all of them. Therefore, the determination in step S406 is "No", and the compression range setting unit 105 selects the next fluorescence signal P17 (S407) and performs the processing after step S403.

[0359] right Figure 26 The same process is repeated for the fluorescent signals P17 to P23 shown. Consequently, the fluorescent signals P15, P18, P20, and P22 are not assigned the size standard marker JS (detected as the first fluorescent signal). Meanwhile, the fluorescent signals P16, P17, P19, P21, and P23 are assigned the size standard marker JS (detected as the second fluorescent signal).

[0360] Then, since the processing of all the fluorescent signals P is completed, the compression range setting unit 105 determines “Yes” in step S406 .

[0361] Then, the compression range setting unit 105 assigns numbers to the fluorescent signals P of the size standard mark JS in order of the frame number from the largest one (S408). Figure 26 As shown, the size standard number "1" is assigned to the fluorescent signal P23 ( Figure 26 Then, the size standard number "2" is assigned to the fluorescent signal P21 ( Figure 26 In addition, the fluorescent signal P19 is assigned the number "3" ( Figure 26 JS3), the fluorescent signal P17 is assigned the number "4" ( Figure 26 Similarly, the fluorescent signal P16 is assigned the number "5" ( Figure 26 The symbol JS5) is the number of the size standard product.

[0362] Next, the compression range setting unit 105 determines whether the maximum value of the number assigned in step S408 is the same as the prescribed number of dimensional standards (S409). The maximum value of the number assigned in step S408 is "5" (symbol JS5). On the other hand, the prescribed number of dimensional standards is 4. Therefore, the maximum value of the assigned number is different from the prescribed number of dimensional standards. Therefore, the compression range setting unit 105 determines "No" in step S409.

[0363] Then, the compression range setting unit 105 deletes the size standard mark JS from the fluorescent signal P assigned a number greater than the predetermined number of the size standard (S411). Figure 27 The fluorescence signal P16 is assigned the symbol "5" (symbol JS5), which is greater than the specified number of size standards, namely "4". Therefore, the compression range setting unit 105 deletes the size standard symbol JS assigned to the fluorescence signal P16. The compression range setting unit 105 then proceeds to step S410. This eliminates the fluorescence signal P16, which was mistakenly identified as the fluorescence signal P caused by the size standard, from the fluorescence signal P caused by the size standard.

[0364] Furthermore, in the second embodiment, in step S408, the compression range setting unit 105 assigns numbers to the fluorescent signals P assigned the size standard mark JS, starting with the highest frame number. However, this is not limiting. The compression range setting unit 105 may also assign numbers to the fluorescent signals P assigned the size standard mark JS, starting with the lowest frame number (corresponding frame number). In this case, in step S411, the compression range setting unit 105 calculates the difference between the number of fluorescent signals P detected with the color of the size standard and the specified number of size standards. The compression range setting unit 105 then deletes the size standard mark JS in order, starting with the lowest frame number, based on this difference.

[0365] In step S411, if the number of fluorescence signals P assigned the marker JS exceeds the number of used size standards, the compression range setting unit 105 deletes the marker JS assigned to the fluorescence signal P. In this case, the compression range setting unit 105 deletes the marker JS assigned to the fluorescence signal P by the excess amount, starting from the corresponding frame number smaller among the fluorescence signals P assigned the marker JS in the fluorescence signal data D25.

[0366] Reference Figure 27In the electrophoresis image EP5 shown, among the fluorescent signals P assigned the mark JS of the size standard, the fluorescent signal P with the smallest frame number is the fluorescent signal P17 assigned the number "4" (symbol JS4). In addition, among the fluorescent signals P assigned the mark S of the size standard, the fluorescent signal P with the largest frame number is the fluorescent signal P23 assigned the mark JS (symbol JS1) with the number "1". Therefore, the compression range setting unit 105 obtains the starting frame number of the fluorescent signal P17, that is, the frame number "2000", as the minimum frame number. In addition, the compression range setting unit 105 obtains the ending frame number of the fluorescent signal P23 with the largest frame number in the fluorescent signal P assigned the mark JS of the size standard as the maximum frame number. As shown Figure 27 As shown in FIG. 4 , the end frame number of the fluorescence signal P23 with the largest frame number is frame number “4500”. Then, the compression range setting unit 105 sets the compression range H from the minimum frame number to the maximum frame number ( S410 ). Figure 27 In the example shown, the compression range H is set to frame numbers "2000" to "4500".

[0367] exist Figure 27 In FIG, the mark JS of the size standard is deleted from the fluorescent signal P16, so the mark JS and the symbol JS5 are omitted.

[0368] In addition, Figure 27 In the figure, the values ​​of "300", "800", "2000", "4000", "4020", and "5000" recorded together with the lead lines on the horizontal axis at the bottom of the paper are frame numbers.

[0369] In this way, the compression range setting unit 105 sets the frame range in which the fluorescent signal P to which the mark JS of the size standard is attached is detected as the compression range H.

[0370] Then, the compression range setting unit 105 sets the compression range H (in Figure 27 In the example shown, the frame numbers "2000" to "4500" are output to the compression ratio calculation unit 106 and the compression unit 107 (step S412).

[0371] Thus, the compression range setting unit 105 uses the characteristic that the fluorescent signal P caused by the primer is detected earlier than the analyte DNA or the size standard to set the compression range H. Furthermore, the compression range setting unit 105 uses the characteristics of the fluorescent signal P caused by the size standard to set the compression range H. The characteristics of the fluorescent signal P caused by the size standard used are as described below.

[0372] (1) The number of fluorescent signals P caused by the size standard is known.

[0373] (2) The fluorescent signal P caused by the size standard is detected in a wider range than the fluorescent signal P caused by the DNA to be analyzed.

[0374] (3) The fluorescent signal P caused by the size standard is detected later than the fluorescent signal P caused by the primer.

[0375] In the second embodiment, by utilizing the features of (1) to (3) above, it is possible to distinguish between the fluorescent signal P caused by the primer and the fluorescent signal P caused by the DNA to be analyzed, and to set the compression range H. Based on the property of (3) above, by setting the range in which the fluorescent signal P caused by the size standard is detected as the compression range H, the fluorescent signal P caused by the primer is excluded from the compression range H.

[0376] (Function of Compression Ratio Calculation Unit 106)

[0377] In the second embodiment, the function of the compression ratio calculation unit 106 is the same as that of the first embodiment. Therefore, the illustration and description of the function of the compression ratio calculation unit 106 in the second embodiment are omitted. In the second embodiment, the compression ratio D27 is also calculated as "0.091".

[0378] (Function of the Compression Unit 107)

[0379] Next, refer to Figure 18 、 Figure 27 and Figure 28 , explaining the function of the compression unit 107. In addition, in the following description, the step numbers are Figure 18 The step number used in .

[0380] First, the compression unit 107 obtains the fluorescence signal data D25 from the color conversion unit 104 (S301). Next, the compression unit 107 obtains the compression range H from the compression range setting unit 105 (S302). Figure 27 The fluorescence signal data D25 and the compression range H shown in FIG. Figure 27 As shown, the compression range H is set from frame number "2000" to frame number "4500".

[0381] Next, the compression unit 107 obtains the compression ratio D27 from the compression ratio calculation unit 106 (S303). As described above, in the second embodiment, the compression ratio D27 is "0.091". Then, in step S304, the compression unit 107 determines whether the frame to be processed is included in the compression range H.

[0382] For example, refer to Figure 27, the frame numbers "4000" to "4020" constituting the fluorescence signal P22 are included in the compression range H. Therefore, when the frames to be processed are included in the frame numbers "4000" to "4020", the compression unit 107 Figure 16 The judgment in step S304 is "yes". Then, the compression unit 107 enters Figure 16 The process of step S305 is then continued. Then, in step S305, the compression unit 107 multiplies the fluorescence signal intensity of the target frame by the compression ratio D27. For example, among frame numbers "4000" to "4020," the fluorescence signal intensity of the frame corresponding to the maximum signal intensity D26 is "360,000." Therefore, when the compression unit 107 multiplies the fluorescence signal intensity of this frame by the compression ratio D27, which is "0.091," the fluorescence signal intensity of the target frame is compressed to "360,000 × 0.091 = 32,767."

[0383] On the other hand, the frame numbers "300" to "800" constituting the fluorescence signal P15 are not included in the compression range H. Therefore, Figure 16 If the judgment in step S304 is "No", the compression unit 107 enters Figure 16 Then, in step S306, the compression unit 107 determines whether the fluorescence signal intensity of the frame being processed is greater than "32767." For frames with fluorescence signal intensities greater than "32767," the compression unit 107 rounds down the fluorescence signal intensity to "32767" (S307). As described above, no compression is performed in step S307. Furthermore, for frames with fluorescence signal intensities less than "32767," the compression unit 107 sets the fluorescence signal intensity to the original value (S308). The compression unit 107 performs steps S306 to S308 on each frame of the electrophoresis image EP (fluorescent signal data D25) outside the compression range H.

[0384] Then, the processing of steps S305, S307, and S308 is performed, and the output is output in step S310. Figure 28 The electrophoresis image EP6 (EP) shown is used as the fluorescence signal compression data D28. Figure 28 In the figure, the dotted line V3 represents the equivalent Figure 27 The fluorescence signal data D25 is compressed so that the fluorescence signal intensity D26 is equal to the maximum value of the fluorescence signal intensity D26 (fluorescence signal intensity of the fluorescence signal P22). Figure 28 The value corresponding to the maximum signal strength D26 becomes the maximum signal strength that can be used in the secondary analysis (in this embodiment, "32676"). That is, the dotted line V3 corresponds to the maximum signal strength that can be used in the secondary analysis. Figure 28In the figure, the values ​​"2000" and "4500" recorded together with the lead lines on the horizontal axis at the bottom of the paper are frame numbers.

[0385] The processing of steps S304 to S308 is performed on each frame constituting the fluorescence signal data D25. Figure 28 The electrophoresis image EP2 shown is equivalent to the fluorescence signal compression data D28. Figure 28 In the figure, the dotted line V3 represents the equivalent Figure 27 The value of the maximum signal intensity D26 (the fluorescence signal intensity of the compressed fluorescence signal P6). Figure 21 As shown, in the compression range H, the fluorescence signal data D25 is compressed so as to be equivalent to Figure 20 The maximum signal intensity value D26 becomes the maximum signal intensity value that can be used in the secondary analysis. In this embodiment, the maximum signal intensity value that can be used in the secondary analysis is "32676." For regions outside the compression range H, the compression unit 107 performs steps S306 to S308. As a result, the fluorescence signals P shown by the fluorescence signals P15 and P16 have portions above the value "32676" removed.

[0386] [Effect]

[0387] According to the second embodiment, in addition to the effects of the first embodiment, the characteristics of the size standard are utilized. Thus, even when using a size standard, the compression ratio D27 can be minimized to maintain a small signal and compress the fluorescence signal data D25 to a value that can be input into the secondary analysis software.

[0388] Furthermore, in the second embodiment, the fluorescent signal P caused by the target DNA and the fluorescent signal P caused by the size standard are detected separately based on the color information of the fluorescent signal P. This makes it possible to easily distinguish the fluorescent signal P caused by the target DNA and the fluorescent signal P caused by the size standard.

[0389] Furthermore, in the second embodiment, the compression range setting unit 105 determines whether the number of fluorescent signals P assigned the size standard marker JS exceeds the number of size standards used. The compression range setting unit 105 then deletes the excess marker JS from the fluorescent signals P assigned the marker JS, starting with the corresponding frame number in the fluorescence signal data D25. Because the fluorescent signals P share the same color as the size standards, fluorescent signals P that are actually caused by the primer may be mistakenly detected as fluorescent signals P from the size standards. Even in such cases, the aforementioned processing can correct the misdetection.

[0390] <2-2nd embodiment>

[0391] Next, refer to Figure 25 、 Figure 29 and Figure 30 Embodiment 2-2 of the present invention will be described.

[0392] Figure 29 and Figure 30 1 is a diagram showing an example of an electrophoresis image EP.

[0393] In the 2-1st embodiment, the characteristics of the fluorescence signal P caused by the size standard are utilized. Thus, a method of processing data in the electrophoresis image EP (fluorescence signal data D25) including the fluorescence signal P caused by the primer is described.

[0394] In contrast, in Embodiment 2-2, similarly to Embodiment 2-1, the characteristics of the fluorescent signal P constituting the size standard are utilized. However, in Embodiment 2-2, a method for processing electrophoresis data in an electrophoresis image EP (fluorescent signal data D25) that does not include the fluorescent signal P due to the primer will be described.

[0395] In the 2-2nd embodiment, the system configuration and operation are the same as those in the 2-1st embodiment. Therefore, the illustration and description of the system configuration and operation in the 2-2nd embodiment will be omitted.

[0396] [effect]

[0397] In the second embodiment, Figure 25 The electrophoresis image EP depicted in step S402 is Figure 29 The case of the electrophoresis image EP7 (EP) shown in FIG. Figure 29 FIG2 shows an electrophoresis image EP7 of the sample D10 to be analyzed. Fluorescence signal data D25 includes fluorescence signals P from the DNA to be analyzed and fluorescence signals P from the size standard. On the other hand, fluorescence signal data D25 does not include fluorescence signals P from primers other than those to be analyzed. Furthermore, in the second embodiment, the size standard comprises four fluorescence signals P. Furthermore, in the electrophoresis image EP7, the color of the fluorescence signals P from the size standard is indicated by a dashed line.

[0398] In addition, Figure 29 In the figure, the numerical values ​​"2000", "4000", "4030", and "4500" recorded together with the lead lines on the horizontal axis at the bottom of the paper represent frame numbers.

[0399] (Function of Compression Range Setting Unit 105)

[0400] Reference Figure 25 and Figure 29 , explaining the function of the compression range setting unit 105 of the second embodiment. In the following description, the step number is Figure 25 The step number shown.

[0401] First, the compression range setting unit 105 acquires the fluorescence signal data D25 from the color conversion unit 104 ( S401 ). Figure 29 FIG. 4 shows the electrophoresis image EP7 drawn by the compression range setting unit 105 in step S402. Figure 29 As shown, electrophoresis image EP7 contains seven fluorescence signals P. The compression range setting unit 105 then searches through these fluorescence signals P, starting with frame number "1," and processes the first detected fluorescence signal P24. This fluorescence signal P24 has the color of the size standard. Therefore, if the determination in step S403 is "yes," the compression range setting unit 105 assigns the size standard label JS to the fluorescence signal P24 (S405).

[0402] Next, in step S406 , the compression range setting unit 105 determines whether the processing of all the fluorescent signals P has been completed by processing the fluorescent signal P24 . Figure 29 The electrophoresis image EP7 is the fluorescence signal P24, not all of it. Therefore, the compression range setting unit 105 determines "No" in step S406. Then, the compression range setting unit 105 selects the fluorescence signal P25 to be detected next (S407) and performs the processing after step S403.

[0403] Reference Figure 29 , the fluorescence signal P25 is not the color of the size standard. Therefore, the compression range setting unit 105 determines "No" in step S403. Then, the compression range setting unit 105 selects the fluorescence signal P26 to be detected next in step S404 (S404) and performs the processing from step S403 onwards.

[0404] Next, the same processing as for the fluorescent signals P24 and P25 is repeated for the fluorescent signals P26 to P30. Consequently, the size standard marker JS is not assigned to the fluorescent signals P25, P27, and P29 (detected as the first fluorescent signal). On the other hand, the size standard marker JS is assigned to the fluorescent signals P24, P26, P28, and P30 (detected as the second fluorescent signal).

[0405] Then, when the processing related to the fluorescent signal P30 is completed, since the processing of step S405 is completed for all fluorescent signals P, the compression range setting unit 105 determines “Yes” in step S406 .

[0406] Then, the compression range setting unit 105 assigns numbers to the fluorescent signals P of the size standard marked with the mark JS, starting from the largest frame number (S408). Figure 29 As shown, the fluorescence signal P30 is numbered "1" (symbol JS1). Similarly, the fluorescence signal P28 is numbered "2" (symbol JS2), the fluorescence signal P26 is numbered "3" (symbol JS3), and the fluorescence signal P24 is numbered "4" (symbol JS4).

[0407] Next, the compression range setting unit 105 determines whether the maximum value of the numbers assigned in step S408 is the same as the specified number of dimension standards (S409). In this embodiment, the maximum value of the numbers assigned in step S408 is "4." On the other hand, the specified number of dimension standards is 4. Therefore, the compression range setting unit 105 determines "yes" in step S409 and proceeds to step S410.

[0408] Then, refer to Figure 29 Among the fluorescence signals P assigned the size standard mark JS, the fluorescence signal P with the smallest frame number is fluorescence signal P24, assigned the number "4" (symbol JS4). Furthermore, among the fluorescence signals P assigned the size standard mark S, the fluorescence signal P with the largest frame number is fluorescence signal P30, assigned the number "1" (symbol JS1). Therefore, the compression range setting unit 105 designates the starting frame number of fluorescence signal P24, i.e., frame number "2000," as the minimum frame number. Furthermore, the ending frame number of fluorescence signal P30, i.e., frame number "4500," as the maximum frame number. The compression range setting unit 105 then sets the range from the minimum frame number to the maximum frame number as compression range H (S410).

[0409] In this way, the compression range setting unit 105 sets the frame range in which the fluorescent signal P to which the mark JS of the size standard is attached is detected as the compression range H.

[0410] Then, the compression range setting unit 105 outputs the compression range H set in step S410 . In the second embodiment, the compression range setting unit 105 outputs the frame number “ 2000 ” to the frame number “ 4500 ” as the compression range H to the compression ratio calculation unit 106 and the compression unit 107 .

[0411] (Function of Compression Ratio Calculation Unit 106)

[0412] Next, refer to Figure 17 and Figure 29 , explaining the function of the compression ratio calculation unit 106. In the following description, the step number is Figure 17 The step number shown.

[0413] First, the compression ratio calculation unit 106 obtains the fluorescence signal data D25 from the color conversion unit 104 (S201). Next, the compression ratio calculation unit 106 obtains the compression range H from the compression range setting unit 105 (S202). As described above, in the second embodiment, the frame numbers "2000" to "5000" are the compression range H. In step S203, the compression ratio calculation unit 106 obtains the maximum signal intensity D26 of the fluorescence signal data D25 included in the compression range H. Figure 29 As shown, the maximum signal intensity value D26 of the fluorescence signal data D25 included in the frame numbers "1" to "5000" is "360000".

[0414] Next, the compression ratio calculation unit 106 calculates the compression ratio D27 in step S204. As described above, the maximum signal strength value D26 is "360000", and the upper limit of the value output by the compression unit 107 is "32767". Therefore, the compression ratio D27 is calculated as "32767 / 360000 = 0.091".

[0415] (Function of the Compression Unit 107)

[0416] Next, refer to Figure 18 、 Figure 29 and Figure 30 , explaining the function of the compression unit 107. In the following description, the step number is Figure 18 The step number shown.

[0417] First, the compression unit 107 obtains the fluorescence signal data D25 from the color conversion unit 104 (S301). Next, the compression unit 107 obtains the compression range H from the compression range setting unit 105 (S302). As described above, in the second embodiment, frame numbers "2000" to "5000" constitute the compression range H. Next, the compression unit 107 obtains the compression ratio D27 from the compression ratio calculation unit 106 (S303). As described above, in the second embodiment, "0.091" is set as the compression ratio D27.

[0418] The compression unit 107 is Figure 18 In step S304, it is determined whether the frame to be processed is included in the compression range H.

[0419] Reference Figure 29, all frames constituting fluorescence signals P24 to P30 are within the compression range H. Therefore, the compression unit 107 determines "yes" in step S304 for all frames constituting fluorescence signals P24 to P30. The compression unit 107 then proceeds to step S305, where it multiplies the fluorescence signal intensity of the target frame by the compression ratio D27 (S305). As a result, the fluorescence signal intensity of the frame corresponding to the maximum signal intensity D26 is compressed to "32767" using "360000 × 0.091."

[0420] Through the process of step S305, the compression unit 107 generates Figure 30 The electrophoresis image EP8 shown is used as the fluorescence signal compressed data D28. Then, in step S310, the compression unit 107 outputs the generated fluorescence signal compressed data D28. Figure 30 In the figure, the dotted line V4 represents the equivalent Figure 29 The value of the maximum signal intensity D26 (fluorescence signal intensity of the fluorescence signal P29). Figure 30 As shown, the fluorescence signal data D25 is compressed so that Figure 29 The value corresponding to the maximum signal strength D26 is the maximum signal strength that can be used in the secondary analysis ("32676" in this embodiment). That is, the dotted line V4 corresponds to the maximum signal strength that can be used in the secondary analysis.

[0421] In addition, Figure 30 In the figure, the numerical values ​​"2000" and "4500" recorded together with the lead lines on the horizontal axis at the bottom of the paper are frame numbers.

[0422] As described above, according to the 2-2 embodiment, the electrophoresis image EP that does not include the fluorescent signal P caused by the primer can also be compressed by the same processing as that of the 2-1 embodiment.

[0423] [Effect]

[0424] According to the second embodiment, in addition to the effects of the first embodiment, the compression ratio D27 can be minimized even when no fluorescent signal due to primers is included in the electrophoresis. Thus, the fluorescent signal data D25 can be compressed to a value that can be input into the secondary analysis software while maintaining a small signal such as the fluorescent signal P due to DNA.

[0425] Example of Secondary Analysis Screen 300

[0426] Figure 31 3 is a diagram showing an example of a secondary analysis screen 300 displayed in this embodiment.

[0427] Figure 31The secondary analysis screen 300 shown is displayed on the output device of the computer executing the secondary analysis software by the secondary analysis software when the secondary analysis is performed. Figure 31 The output device of the secondary analysis screen 300 shown can be Figure 5 The output device 155 shown may not be.

[0428] like Figure 31 As shown in FIG. 3 , an image of the fluorescence signal compression data D28 is displayed on the secondary analysis screen 300. Figure 31 Display Figure 21 The image shown is of compressed fluorescence signal data D28, but it can also be displayed Figure 23 、 Figure 28 、 Figure 30 The user performs secondary analysis by referring to the fluorescent signals P25, P27, and P29 caused by DNA displayed on the secondary analysis screen 300.

[0429] In such a secondary analysis screen 300 , fluorescent signals P25 , P27 , and P29 caused by DNA, which have a small fluorescent signal intensity relative to the fluorescent signals P1 to P3 caused by primers, are displayed in an appropriate size, thereby enabling the user to perform appropriate secondary analysis.

[0430] The present invention is not limited to the above-described embodiments and includes various variations. For example, the above-described embodiments are described in detail to facilitate understanding of the present invention and are not necessarily limited to having all the structures described. In addition, a portion of the structure of a certain embodiment can be replaced with the structure of another embodiment, and the structure of another embodiment can be added to the structure of a certain embodiment. In addition, with respect to a portion of the structure of each embodiment, other structures can be added, deleted, or replaced.

[0431] In this embodiment, the compression range H in the fluorescence signal data D25 is compressed, and the area outside the compression range H is not compressed. However, the present invention is not limited thereto, and the fluorescence signal data D25 may be uniformly compressed at the compression rate D27.

[0432] In addition, the above-mentioned structures, functions, signal accumulator 101 to compressor 107, storage device 153, etc. may be partially or entirely implemented in hardware by, for example, designing an integrated circuit. Figure 5As shown, the aforementioned structures and functions can also be implemented by software by a processor such as a CPU interpreting and executing programs that implement the functions. Information such as programs, tables, and files that implement the functions can be stored not only on the HD but also on a storage device such as memory 151 or an SSD, or on a recording medium such as an IC (Integrated Circuit) card, an SD (Secure Digital) card, or a DVD (Digital Versatile Disc).

[0433] In addition, in each embodiment, the control lines and information lines are shown as lines considered necessary for explanation, and not all control lines and information lines are shown in the product. In reality, it can be considered that almost all components are connected to each other.

[0434] Explanation of symbols

[0435] 1 electrophoresis system;

[0436] 10. Processing device (electrophoresis data processing device);

[0437] 20 electrophoresis device;

[0438] 30 external memory;

[0439] 101 signal accumulation unit (software binning processing unit);

[0440] 102 fluorescence correction unit (fluorescence signal data generation unit);

[0441] 103 pseudo inverse matrix generating unit (fluorescence signal data generating unit);

[0442] 104 color conversion unit (fluorescence signal data generation unit);

[0443] 105 compression range setting unit;

[0444] 106 compression ratio calculation unit;

[0445] 107 compression unit;

[0446] 155 output device;

[0447] 211 Light Receiving Department;

[0448] 211A light receiving element;

[0449] 212 horizontal register unit;

[0450] 212A horizontal register;

[0451] 213 sum gate;

[0452] 300 secondary analysis screen;

[0453] B, B1~BN boxes;

[0454] C, C1~CL soft box;

[0455] D10: Analytical sample (mixed with primers);

[0456] D10a: Analytical sample (mixed with primers and size standards);

[0457] D11 analyzes the sample signal of the object;

[0458] D12 analyzes the cumulative signal of the sample;

[0459] D25 fluorescence signal data;

[0460] D26: Maximum signal intensity (maximum value of the fluorescence signal intensity contained in the compression range); D27: Compression ratio;

[0461] D28 fluorescence signal compression data;

[0462] EP, EP1 to EP8 electrophoresis images;

[0463] H compression range;

[0464] JN Mark;

[0465] JS, JS1 to JS5 markers (markers assigned to the fluorescent signal determined to be the second fluorescent signal);

[0466] JY, JN markings;

[0467] P fluorescence signal;

[0468] P1-P3 fluorescence signals (second fluorescence signals);

[0469] P4 to P14 fluorescence signals (first fluorescence signals);

[0470] P15 and P16 fluorescence signals;

[0471] Fluorescence signals of P17, P19, P21, P23, P24, P26, P28, and P30 (second fluorescence signals); Fluorescence signals of P18, P20, P22, P25, P27, and P29 (first fluorescence signals);

[0472] V1 to V4 dotted lines (equivalent to the maximum signal strength that can be used in the secondary analysis);

[0473] S101 to S112 compression range setting processing (compression range setting step);

[0474] S201 to S205 compression ratio calculation processing (compression ratio calculation step);

[0475] S301-S310 compression processing (compression step);

[0476] S401 to S412 are compression range setting processing (compression range setting step).

Claims

1. An electrophoresis system, characterized in that: have: electrophoresis device; a software binning processing unit that obtains, from the electrophoresis apparatus, signals related to the sample to be analyzed that have been subjected to hardware binning, namely, the sample to be analyzed signal, and signals related to the matrix standard that have been subjected to hardware binning, namely, the matrix standard signal, and performs software binning on the sample to be analyzed signal and the matrix standard signal; a fluorescence signal data generating unit for generating fluorescence signal data, which is data related to the fluorescence signal intensity in each frame, based on the analysis target sample signal and the matrix standard signal subjected to the software binning; a compression range setting unit that detects, with respect to the fluorescence signals included in the fluorescence signal data, a first fluorescence signal caused by the analysis target and a second fluorescence signal caused by sources other than the analysis target, and sets a compression range for a frame of the fluorescence signal data based on the detection result; a compression ratio calculation unit that calculates a compression ratio based on a maximum value of the fluorescence signal intensity included in the compression range and a maximum value of the signal intensity that can be used in the secondary analysis; as well as A compression unit compresses the fluorescence signal data based on the compression rate to generate fluorescence signal compression data, and outputs the generated fluorescence signal compression data.

2. The electrophoresis system according to claim 1, characterized in that The second fluorescent signal is a fluorescent signal caused by the primer, The compression range setting unit sets the compression range based on a frame later than a frame in which the second fluorescent signal is detected.

3. The electrophoresis system according to claim 2, characterized in that: The compression range setting unit distinguishes and detects the second fluorescent signal caused by the primer and the first fluorescent signal based on at least one of a width, an area, and a last frame including the fluorescent signal of the fluorescent signal included in the fluorescent signal data.

4. The electrophoresis system according to claim 1, wherein: The compression range setting unit detects a fluorescent signal from the size standard as the second fluorescent signal, and sets a frame range in which the second fluorescent signal is detected as the compression range.

5. The electrophoresis system according to claim 4, characterized in that: The compression range setting unit distinguishes and detects the first fluorescent signal and the second fluorescent signal based on color information of the fluorescent signal.

6. The electrophoresis system according to claim 5, characterized in that: The compression range setting unit performs the following processing: assigning a label to the fluorescent signal determined to be the second fluorescent signal; When the number of the fluorescent signals assigned the marker exceeds the number of the size standards used, the markers assigned to the fluorescent signals are deleted from the fluorescent signal data in descending order of corresponding frame numbers of the fluorescent signals assigned the marker by an amount equal to the excess; as well as The frame range in which the fluorescent signal to which the marker is assigned is detected is set as the compression range.

7. The electrophoresis system according to claim 1, wherein: The compression unit outputs the analysis target sample signal and the compression ratio in addition to the fluorescence signal compression data.

8. An electrophoresis data processing device, characterized in that: have: a software binning processing unit that obtains, from the electrophoresis apparatus, signals related to the sample to be analyzed, which have been subjected to hardware binning, i.e., the sample to be analyzed signal, and signals related to the matrix standard to have been subjected to hardware binning, i.e., the matrix standard signal, and performs software binning on the sample to be analyzed signal and the matrix standard signal; a fluorescence signal data generating unit for generating fluorescence signal data, which is data related to the fluorescence signal intensity in each frame, based on the analysis target sample signal and the matrix standard signal subjected to the software binning; a compression range setting unit that detects, for the fluorescence signals included in the fluorescence signal data, a first fluorescence signal caused by the analysis object and a second fluorescence signal caused by sources other than the analysis object, and sets a compression range for a frame of the fluorescence signal data based on a result of the detection; a compression ratio calculation unit that calculates a compression ratio based on a maximum value of the fluorescence signal intensity included in the compression range and a maximum value of the signal intensity that can be used in a secondary analysis; as well as A compression unit compresses the fluorescence signal data based on the compression rate to generate fluorescence signal compression data, and outputs the generated fluorescence signal compression data.

9. A method for processing electrophoresis data, characterized in that: The electrophoresis system obtains, from the electrophoresis apparatus, signals related to the target sample subjected to hardware binning, namely, the target sample signal, and signals related to the matrix standard subjected to hardware binning, namely, the matrix standard signal, and generates, for the target sample signal and the matrix standard signal, data related to the fluorescence signal intensity in each frame, namely, fluorescence signal data, based on the target sample signal subjected to software binning and the matrix standard signal subjected to the software binning. The electrophoresis system performs the following steps: a compression range setting step of detecting, for the fluorescence signals included in the fluorescence signal data, a first fluorescence signal caused by the analysis object and a second fluorescence signal caused by something other than the analysis object, and setting a compression range for a frame of the fluorescence signal data based on the detection result; a compression ratio calculation step of calculating a compression ratio based on a maximum value of the fluorescence signal intensity included in the compression range and a maximum value of the signal intensity that can be used in the secondary analysis; as well as The compression step compresses the fluorescence signal data based on the compression rate to generate fluorescence signal compressed data, and outputs the generated fluorescence signal compressed data.

Images