Microchip electrophoresis device

Abstract

A microchip electrophoresis device is provided with: a sample setting unit for setting at least one sample and at least one standard sample; at least one microchip having a flow path for electrophoresis therein; an introduction device that introduces the separation buffer, the sample, and the standard sample into the flow path; a voltage applying device that applies a voltage to the flow path; a detection unit that acquires analysis data for electrophoretic analysis in the flow path; and a controller that controls the operation of the introduction device and the voltage application device, the controller being provided with: a standard data storage unit that stores standard data obtained by performing electrophoretic analysis on the standard sample under predetermined conditions; and a chip determination unit that performs chip determination before performing electrophoretic analysis on the sample by performing electrophoretic analysis on the standard sample using each microchip under predetermined conditions, acquiring analysis data of the standard sample by the detection unit, and comparing the acquired analysis data with standard data of the standard sample, it is determined whether or not the state of each microchip is suitable for electrophoretic analysis.

Description

[0001] This application is a divisional application of the application with the application date of January 6, 2022, application number 202210010674.4, and invention title "Microchip Electrophoresis Device". Technical Field

[0002] The present invention relates to a microchip electrophoresis device. Background Art

[0003] There is known a microchip electrophoresis device that uses a microchip for electrophoresis analysis (see Patent Document 1). The microchip electrophoresis device can set a plurality of microchips and can use the plurality of microchips to simultaneously and parallelly perform electrophoresis analysis of many samples.

[0004] Prior Art Documents

[0005] Patent Documents

[0006] Patent Document 1: Japanese Unexamined Patent Application Publication No. 2020-128904 Summary of the Invention

[0007] Problems to be Solved by the Invention

[0008] In a microchip electromigration device, when the performance of the microchip deteriorates or the separation buffer solution filled in the microchip is incorrect, even if electrophoresis analysis is performed using the microchip, correct analysis data cannot be obtained. However, hitherto, in most cases, such an adverse condition has been noticed only after verifying the analysis data obtained by performing electrophoresis analysis on a sample, and thus there is a problem that incorrect analysis data is obtained in such a case, wasting time and samples.

[0009] The present invention has been completed in view of the above problems, and an object thereof is to prevent electrophoresis analysis from being performed using a microchip in a state that is not suitable for use in electrophoresis analysis.

[0010] Solutions to the Problems

[0011] The microchip electrophoresis device according to the present invention includes: a sample setting unit that sets at least one sample and at least one standard sample that are objects of electrophoresis analysis; at least one microchip having a flow path for performing electrophoresis inside; an introduction device that introduces a separation buffer, a sample, and a standard sample into the flow path in the microchip; a voltage application device that applies a voltage to the flow path in the microchip; a detection unit that acquires analysis data of electrophoresis analysis in the flow path of the microchip; and a controller that controls the operations of the introduction device and the voltage application device. Further, the controller includes: a standard data storage unit that stores standard data obtained by performing electrophoresis analysis on a standard sample under specified conditions; and a chip determination unit configured to perform the following chip determination before performing electrophoresis analysis on a sample set in the sample setting unit: performing electrophoresis analysis on the standard sample under the specified conditions using each of the at least one microchip, acquiring analysis data for the standard sample through the detection unit, and comparing the acquired analysis data with the standard data for the standard sample, thereby determining whether the state of each of the at least one microchip is suitable for performing electrophoresis analysis.

[0012] Effects of the Invention

[0013] In the microchip electrophoresis device according to the present invention, the controller is configured to store standard data obtained by performing electrophoresis analysis on a standard sample under specified conditions. Before performing electrophoresis analysis on a sample, electrophoresis analysis is performed on the standard sample under the specified conditions using each of the at least one microchip, and analysis data is acquired. The acquired analysis data is compared with the standard data, thereby determining whether the state of each of the at least one microchip is suitable for performing electrophoresis analysis. Therefore, it is possible to prevent electrophoresis analysis from being performed using a microchip in a state that is not suitable for performing electrophoresis analysis. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Figure 1 It is a schematic structural diagram showing an example of an embodiment of the microchip electrophoresis device.

[0015] Figure 2 It is a flowchart for explaining an example of the operation of the above embodiment.

[0016] Figure 3 It is a diagram showing an example of a sample registration screen in the above embodiment.

[0017] Figure 4 It is an example of an electrophoresis pattern for explaining the relationship between the type of separation buffer and the analysis data of the standard sample.

[0018] Figure 5This is an example of an electrophoresis pattern for explaining the relationship between the types of separation buffers and the analysis data of standard specimens.

[0019] Explanation of Reference Numerals

[0020] 2-1 to 2-4: Microchips; 4: Specimen setting section; 6: Separation buffer setting section; 8: Introduction device; 10: Voltage application device; 12: Detection section; 14: Controller; 16: Standard data storage section; 18: Chip determination section; 20: Schedule determination section; 22: Analysis execution section. Detailed Description of the Invention

[0021] Hereinafter, an embodiment of a microchip electrophoresis apparatus according to the present invention will be described with reference to the accompanying drawings.

[0022] As Figure 1 shown, the microchip electrophoresis apparatus of this embodiment includes a plurality of microchips 2-1 to 2-4, a specimen setting section 4, a separation buffer setting section 6, an introduction device 8, a voltage application device 10, a detection section 12, and a controller 14. Although not shown in the drawings, the microchips 2-1 to 2-4 each have a flow path for performing electrophoresis inside, and the microchips 2-1 to 2-4 each have ports at both ends of the flow path on the upper surface. In addition, in this embodiment, four microchips 2-1 to 2-4 are provided, but the present invention is not limited thereto, and one or more microchips may be provided.

[0023] In the specimen setting section 4, one or more specimens to be subjected to electrophoresis analysis and one or more standard specimens serving as a reference for indicating the size of the components in the specimens are set. The specimens and the standard specimens are set in a state of being accommodated in the holes provided in the well plate.

[0024] One or more types of separation buffers are set in the separation buffer setting section 6 in a state of being accommodated in a container.

[0025] The introduction device 8 is a device that includes a dispensing probe and a pipette tip and is used to introduce specimens, standard specimens, and separation buffers into the microchips 2-1 to 2-4. An example of the specific structure of the introduction device 8 is omitted here. For example, it can be set to a structure equivalent to that disclosed in Japanese Patent Application Laid-Open No. 2020-128904.

[0026] The voltage application device 10 is a device that applies a voltage to both ends of the flow path of each of the microchips 2-1 to 2-4 to perform specimen introduction and specimen electrophoresis.

[0027] The detection section 12 optically detects the components separated by electrophoresis in the flow paths of the microchips 2-1 to 2-4. The detection section 12 includes, for example, an excitation light source for irradiating excitation light to the components stained with fluorescence, and a light sensor for detecting the fluorescence emitted from the excited fluorescent dye.

[0028] The controller 14 controls the operations of the introduction device 8 and the voltage application device 10, and performs various arithmetic processes based on the detection signals obtained by the detection unit 12. The controller 14 can be implemented by one or more computer devices including a CPU (central processing unit) and an information storage device.

[0029] The controller 14 includes a standard data storage unit 16, a chip determination unit 18, a schedule determination unit 20, and an analysis execution unit 22. The standard data storage unit 16 is a function implemented by a part of the storage area of the information storage device, and the chip determination unit 18, the schedule determination unit 20, and the analysis execution unit 22 are functions implemented by the CPU executing a prescribed program.

[0030] The standard data storage unit 16 stores the analysis data obtained by performing electrophoresis analysis on a standard specimen under prescribed conditions as standard data. There are multiple types of separation buffers such as DNA-500, DNA-1000, and DNA-12000, and there are standard specimens corresponding to various types of separation buffers. The standard data storage unit 16 stores the analysis data obtained under prescribed conditions (prescribed applied voltage, etc.) using the corresponding separation buffer for each standard specimen as the standard data for each standard specimen. The standard data can include the number of errors, the number of warnings, the low molecular weight marker time, the high molecular weight marker time, the low molecular weight marker height, the high molecular weight marker height, the current value of each port during loading, the current value of each port during electrophoresis separation, the baseline height, the high molecular weight marker theoretical plate number, the noise amplitude, etc. The standard data can also include the appearance time of each peak in the electrophoresis pattern and / or the number of peaks in the electrophoresis pattern.

[0031] The chip determination unit 18 is configured to perform chip determination before starting the electrophoresis analysis of the specimen. In this chip determination, electrophoresis analysis is performed on the standard specimen in the microchips 2-1 to 2-4 to obtain the analysis data for the standard specimen, and the obtained analysis data is compared with the standard data stored in the standard data storage unit 16, thereby determining whether the states of the microchips 2-1 to 2-4 are suitable for use in the electrophoresis analysis of the specimen. In the chip determination, each item of the analysis data obtained by the electrophoresis analysis of the standard specimen is compared with each item of the standard data to determine whether the deviation is within the allowable range. For example, it is determined whether the relative deviation of the positions of the peaks in the electrophoresis pattern of the analysis data from the positions of the peaks in the electrophoresis pattern of the standard data is within the allowable range. If it exceeds the allowable range, it is determined that the microchip cannot be used (not suitable for use in electrophoresis analysis). In addition, in the case where the number of peaks in the electrophoresis pattern of the analysis data is inconsistent with the number of peaks in the electrophoresis pattern of the standard data, it is also determined that the microchip cannot be used.

[0032] The scheduling table determination unit 20 determines the analysis scheduling table in the following manner: The electrophoresis analysis of the sample is performed using the microchips 2-1 to 2-4 that have been determined by the chip determination unit 18 to be suitable for use in the electrophoresis analysis of the sample. The analysis scheduling table is used to specify in what order each of a plurality of samples is to be subjected to electrophoresis analysis using which microchip under what conditions.

[0033] In the present embodiment, the analysis scheduling table is temporarily created when a sample is registered with the controller 14. When the chip determination unit 18 determines that all of the microchips 2-1 to 2-4 are suitable for use in the electrophoresis analysis of the sample, the scheduling table determination unit 20 directly determines the analysis scheduling table that is temporarily created when the sample is registered. On the other hand, when the chip determination unit 18 determines that a certain microchip among the microchips 2-1 to 2-4 is not suitable for use in the electrophoresis analysis of the sample, the scheduling table determination unit 20 rearranges and determines the analysis scheduling table in such a way that only the microchips that have been determined to be suitable for use in the electrophoresis analysis are used to perform the electrophoresis analysis of the sample.

[0034] The analysis execution unit 22 is configured to perform the electrophoresis analysis of the sample in accordance with the analysis scheduling table determined by the scheduling table determination unit 20.

[0035] Refer to Figure 1 Also refer to Figure 2 the flowchart of to illustrate an example of the operation of the present embodiment.

[0036] First, a sample is registered with the controller 14 (step 101). The sample is registered on a sample registration screen displayed on a display (not shown) configured to be able to communicate with the controller 14.

[0037] Figure 3 is an example of the sample registration screen. On the left side of the sample registration screen, a well plate for accommodating samples and standard samples in each well is displayed, and on the right side, registration information indicating in what order which microchip (chip) is to be used and which type of separation buffer is to be used to perform electrophoresis of the samples or standard samples accommodated in each well of the well plate is displayed as the analysis scheduling table. The analysis scheduling table for the sample can be arbitrarily determined by the user. The analysis scheduling table for the standard sample can be automatically registered before the analysis scheduling table for the sample, or a display prompting the user to perform such registration can be made.

[0038] When the sample registration is completed and the user inputs an instruction to start the analysis to the controller 14 (step 102), the chip determination unit 18 performs electrophoresis analysis of the standard sample in each of the microchips 2-1 to 2-4 (step 103), and obtains analysis data for the standard sample in each of the microchips 2-1 to 2-4. Then, the chip determination unit 18 determines whether the states of the microchips 2-1 to 2-4 are suitable for use in electrophoresis analysis by comparing each analysis data with the corresponding standard data stored in the standard data storage unit 16 (step 104).

[0039] When the result of the chip determination performed by the chip determination unit 18 is that there is a microchip that can be used in the electrophoresis analysis of the sample (Yes in step 105), the schedule determination unit 106 determines an analysis schedule such that the electrophoresis analysis of the sample is performed using only the available microchips (step 106). The analysis execution unit 22 performs the electrophoresis analysis of the sample according to the analysis schedule determined by the schedule determination unit 20 (step 107).

[0040] On the other hand, when it is determined by the chip determination unit 18 that all the microchips cannot be used in the electrophoresis analysis of the sample (No in step 105), the analysis of the sample is aborted (step 108). A warning or the like can be issued to the user when the analysis of the sample is aborted, so as to prompt the user to replace the microchip, confirm the setting position of the separation buffer, etc.

[0041] As described above, before starting the electrophoresis analysis of the sample, a chip determination is performed to determine whether each of the microchips 2-1 to 2-4 is in a state that can be used in electrophoresis analysis, and the unusable microchips are excluded to determine the analysis schedule, so that it is possible to prevent useless electrophoresis analysis from being performed using unusable microchips.

[0042] In addition, in the chip determination, by evaluating the correlation of the peak positions in the electrophoresis pattern and / or comparing the number of peaks, it is possible to detect errors such as a decrease in the performance of the microchip and a wrong separation buffer.

[0043] Figure 4 and Figure 5 are the verification results of the relationship between the combination of the standard sample and the separation buffer and the peak position, respectively. Figure 4 (A) of Figure 5 (A) of Figure 4 (B) of Figure 5 (B) of Figure 4 (C) ofFigure 5 (C) is an electrophoretogram obtained by performing electrophoresis analysis on a standard sample for DNA-1000 using DNA-12000 (separation buffer). In Figure 4 , the horizontal axis represents the migration time (seconds), and the vertical axis represents the signal intensity (mV). In Figure 5 , the horizontal axis represents the migration time index (%), and the vertical axis represents the signal intensity (mV).

[0044] In Figure 4 and Figure 5 , when comparing (A) to (C) respectively, compared with the case where electrophoresis analysis of the standard sample for DNA-1000 is performed using DNA-1000, when electrophoresis analysis of the standard sample for DNA-1000 is performed using DNA-500, the positions of all the peaks are delayed as a whole. Compared with the case where electrophoresis analysis of the standard sample for DNA-1000 is performed using DNA-1000, when electrophoresis analysis of the standard sample for DNA-1000 is performed using DNA-12000, the positions of all the peaks are advanced as a whole. Therefore, it is possible to determine whether the combination of the standard sample and the separation buffer is correct by evaluating the positions and the number of peaks in the electrophoretogram.

[0045] The embodiments described above only show an example of the embodiments of the microchip electrophoresis device according to the present invention. The embodiments of the microchip electrophoresis device according to the present invention are as follows.

[0046] In one embodiment of the microchip electrophoresis device according to the present invention, it includes: a sample setting unit that sets at least one sample and at least one standard sample to be subjected to electrophoresis analysis; at least one microchip having a flow path for performing electrophoresis inside; an introduction device for introducing a separation buffer, a sample, and a standard sample into the flow path in the microchip; a voltage application device for applying a voltage to the flow path in the microchip; a detection unit for obtaining analysis data of electrophoresis analysis in the flow path of the microchip; and a controller for controlling the operations of the introduction device and the voltage application device. Among them, the controller includes: a standard data storage unit that stores standard data obtained by performing electrophoresis analysis on a standard sample under specified conditions; and a chip determination unit configured to perform the following chip determination before performing electrophoresis analysis on the sample set in the sample setting unit: performing electrophoresis analysis on the standard sample under the specified conditions using each of the at least one microchip, obtaining analysis data for the standard sample through the detection unit, and comparing the obtained analysis data with the standard data for the standard sample, thereby determining whether the states of the at least one microchip are suitable for performing electrophoresis analysis.

[0047] In the first mode of the above-described embodiment, the chip determination performed by the chip determination unit includes an evaluation of the correlation between the peak positions in the analysis data obtained by electrophoresis analysis of the standard sample and the peak positions in the standard data. In this way, it is possible to detect errors such as a reduction in the performance of the microchip and an incorrect combination of the standard sample and the separation buffer.

[0048] In the second mode of the above-described embodiment, the chip determination performed by the chip determination unit includes a comparison of the number of peaks in the analysis data obtained by electrophoresis analysis of the standard sample and the number of peaks in the standard data. In this way, it is possible to detect errors such as a reduction in the performance of the microchip and an incorrect combination of the standard sample and the separation buffer. This second mode can be combined with the above-described first mode.

[0049] In the third mode of the above-described embodiment, the controller further includes an analysis execution unit configured to, after the chip determination performed by the chip determination unit is completed, perform electrophoresis analysis on the sample provided in the sample provision unit using the microchip determined by the chip determination unit to be suitable for use in electrophoresis analysis. In this way, it is possible to prevent electrophoresis analysis of the sample from being performed using a microchip that is not suitable for use in electrophoresis analysis. This third mode can be combined with the above-described first mode and / or second mode.

[0050] In the above-described third mode, the controller further includes a schedule determination unit that, after the chip determination performed by the chip determination unit is completed, determines an analysis schedule in such a way that electrophoresis analysis of the sample provided in the sample provision unit is performed only using the microchip determined by the chip determination unit to be suitable for use in electrophoresis analysis, and the analysis execution unit is configured to perform electrophoresis analysis of the sample according to the analysis schedule determined by the schedule determination unit. In this way, in the case where there is a microchip that is not suitable for use in electrophoresis analysis of the sample, an analysis schedule for excluding such a microchip is automatically determined, so there is no need for the user to create an analysis schedule, and the workload of the user is reduced.

Claims

1. A microchip electrophoresis device, comprising: A sample setting unit that sets at least one sample and at least one standard sample that are objects of electrophoresis analysis; A plurality of microchips, each of which has a flow path for performing electrophoresis inside; An introduction device for introducing separation buffer, samples, and standard samples into the respective flow paths in the plurality of microchips; A voltage application device for applying a voltage to the respective flow paths in the plurality of microchips; A detection unit for acquiring analysis data of electrophoresis analysis in the respective flow paths of the plurality of microchips; And A controller for controlling the operations of the introduction device and the voltage application device, wherein there are a plurality of types of separation buffers, and there are a plurality of types of standard samples corresponding to the plurality of types of separation buffers respectively, The controller includes: A standard data storage unit that stores standard data obtained by performing electrophoresis analysis on the correct combination of the separation buffer and the standard sample under specified conditions; and A chip determination unit configured to perform the following chip determination before performing electrophoresis analysis on the sample set in the sample setting unit: use each of the plurality of microchips to perform electrophoresis analysis on the standard sample corresponding to the separation buffer that should be filled in the respective flow paths of the plurality of microchips among the plurality of types of standard samples under the specified conditions, acquire analysis data for this standard sample through the detection unit, and compare the acquired analysis data with the standard data for this standard sample, thereby determining whether the states of the respective plurality of microchips are suitable for performing electrophoresis analysis by filling the correct separation buffer in the flow path, wherein the standard data includes at least one of the number of errors, the number of warnings, the current value of each port during loading, the current value of each port during electrophoresis separation, the baseline height, and the noise amplitude.

2. The microchip electrophoresis device according to claim 1, wherein, The chip determination performed by the chip determination unit includes an evaluation of the correlation between the peak positions in the analysis data obtained through the electrophoresis analysis of the standard sample and the peak positions in the standard data.

3. The microchip electrophoresis device according to claim 1, wherein, The chip determination performed by the chip determination unit includes a comparison of the number of peaks in the analysis data obtained through the electrophoresis analysis of the standard sample and the number of peaks in the standard data.

4. The microchip electrophoresis device according to any one of claims 1 to 3, wherein, The controller further includes an analysis execution unit configured to: after the chip determination performed by the chip determination unit is completed, use the microchips determined by the chip determination unit to be suitable for use in electrophoresis analysis to perform electrophoresis analysis on the samples set in the sample setting unit.

5. The microchip electrophoresis device according to claim 4, wherein, The controller further includes a schedule determination unit that, after the chip determination by the chip determination unit is completed, determines an analysis schedule in such a manner that electrophoresis analysis of a sample provided in the sample provision unit is performed only using the microchips determined by the chip determination unit to be suitable for use in electrophoresis analysis. The analysis execution unit is configured to execute electrophoresis analysis of a sample according to the analysis schedule determined by the schedule determination unit.

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