Electrophoresis device, control method for electrophoresis device, and control program for electrophoresis device

Abstract

In this electrophoresis device, a processor executes first resistance value derivation processing or second resistance value derivation processing to derive an electrical resistance value of a branch flow passage between a pair of flow passage ends, before a sample is split, wherein: the first resistance value derivation processing is processing for deriving the electrical resistance value on the basis of a measured value obtained by applying an applied voltage for investigation to the pair of flow passage ends; the second resistance value derivation processing is processing for deriving the electrical resistance value on the basis of a measured value obtained by applying an applied current for investigation to the pair of flow passage ends; and a voltage or current applied to the pair of flow passage ends is controlled on the basis of the electrical resistance value derived by means of the first resistance value derivation processing or the second resistance value derivation processing.

Description

Electrophoretic device, control method for electrophoretic device, and control program for electrophoretic device

[0001] The present disclosure relates to an electrophoretic device, a control method for an electrophoretic device, and a control program for an electrophoretic device.

[0002] Electrophoresis devices using microchannel chips have been known. For example, a technique is known in which a sample is concentrated by isotachophoresis to form a concentrated layer, and then the isotachophoresis is switched to capillary electrophoresis to separate specific components contained in the concentrated layer (see, for example, JP 2019-158520 A).

[0003] However, for example, subtle differences in the state of the reagent can cause differences in resistance, which can lead to changes in electrophoresis conditions. Also, differences in the dimensions between microchannels can cause differences in resistance, which can lead to changes in electrophoresis conditions. When electrophoresis conditions change in this way, measurement accuracy can be reduced.

[0004] The present disclosure provides an electrophoresis apparatus, a control method for an electrophoresis apparatus, and a control program for an electrophoresis apparatus that can suppress changes in electrophoresis conditions due to variations in the state of a reagent or between microchannels.

[0005] A first aspect of the present disclosure is an electrophoresis device for separating a sample using a micro-channel chip having a channel formed therein, the channel including three or more channel ends, one or more branch points, and a plurality of branch channel branches at the branch points and connected to each of the channel ends, the channel through which the sample moves by electrophoresis when a voltage or current is applied to a pair of channel ends selected from the plurality of channel ends, the electrophoresis device including at least one processor, the processor performing a first resistance value derivation process or a second resistance value derivation process to derive an electrical resistance value of a branch channel between the pair of channel ends before separating the sample, the first resistance value derivation process being a process of deriving an electrical resistance value based on a measured value obtained by applying an investigation voltage to the pair of channel ends, and the second resistance value derivation process being a process of deriving an electrical resistance value based on a measured value obtained by applying an investigation current to the pair of channel ends, and the processor controlling the voltage or current applied to the pair of channel ends based on the electrical resistance value derived by the first resistance value derivation process or the second resistance value derivation process.

[0006] A second aspect of the present disclosure is a process in which, in the first aspect, the first resistance value derivation process applies an investigation-use applied voltage to a pair of flow path ends, obtains, as measured values, a measured current value of a current flowing between the pair of flow path ends due to the application of the applied voltage, and a first measured voltage value which is a voltage generated at a branch point between the pair of flow path ends due to the application of the applied voltage, and derives an electrical resistance value based on the investigation-use applied voltage value, the measured current value, and the first measured voltage value; and the second resistance value derivation process may be a process in which an investigation-use applied current is applied to the pair of flow path ends, obtains, as measured values, a second measured voltage value of a voltage generated between the pair of flow path ends due to the application of the applied current, and a third measured voltage value which is a voltage generated at a branch point between the pair of flow path ends due to the application of the applied current, and derives an electrical resistance value based on the investigation-use applied current value, the second measured voltage value, and the third measured voltage value.

[0007] A third aspect of the present disclosure is that in the first aspect, the first resistance value derivation process may be a process of sequentially applying an investigation voltage to a plurality of pairs of flow path ends selected from the flow path ends, obtaining measured current values ​​of currents flowing through each of the plurality of pairs of flow path ends due to the application of the applied voltage as measured values, and deriving an electrical resistance value based on the investigation applied voltage value and the measured current value of each of the pair of flow path ends; and the second resistance value derivation process may be a process of sequentially applying an investigation current to a plurality of pairs of flow path ends selected from the flow path ends, obtaining measured voltage values ​​of voltages generated in each of the plurality of pairs of flow path ends due to the application of the applied current as measured values, and deriving an electrical resistance value based on the investigation applied current value and the measured voltage value of each of the pair of flow path ends.

[0008] A fourth aspect of the present disclosure is that, in the first aspect, the applied voltage or current applied to the pair of channel ends when separating the sample may include an applied voltage or current for isotachophoresis when the sample is moved by isotachophoresis as the electrophoresis, and an applied voltage or current for capillary electrophoresis when the sample is moved by capillary electrophoresis as the electrophoresis, and the applied voltage value or applied current value for investigation may be 10% or less of the applied voltage value or applied current value for capillary electrophoresis.

[0009] A fifth aspect of the present disclosure is related to the first aspect, wherein the application time for applying a voltage or current to the pair of channel ends when separating a sample may include an application time for isotachophoresis when the electrophoresis is used to move the sample, and an application time for capillary electrophoresis when the electrophoresis is used to move the sample, and the application time for applying the investigation voltage or investigation current may be 10% or less of the application time for capillary electrophoresis.

[0010] A sixth aspect of the present disclosure is a control method for an electrophoresis device that separates a sample using a micro-channel chip having a channel formed therein, the channel including three or more channel ends, one or more branch points, and a plurality of branch channel ends branched by the branch points and connected to each of the channel ends, and through which a sample moves by electrophoresis when a voltage or current is applied to a pair of channel ends selected from the plurality of channel ends, the control method comprising: the electrophoresis device including a processor; and the processor executing a first resistance value derivation process or a second resistance value derivation process to derive an electrical resistance value of a branch channel between the pair of channel ends before separating the sample; the first resistance value derivation process is a process of deriving an electrical resistance value based on a measured value obtained by applying an investigation voltage to the pair of channel ends; and the second resistance value derivation process is a process of deriving an electrical resistance value based on a measured value obtained by applying an investigation current to the pair of channel ends; and the voltage or current to be applied to the pair of channel ends is controlled based on the electrical resistance value derived by the first resistance value derivation process or the second resistance value derivation process.

[0011] A seventh aspect of the present disclosure is a control program for an electrophoresis device, the control program causing a computer to function as an electrophoresis device that separates samples using a micro-channel chip in which a channel is formed, the channel including three or more channel ends, one or more branch points, and a plurality of branch channel branches at the branch points and connected to each of the channel ends, and in which a voltage or current is applied to a pair of channel ends selected from the plurality of channel ends, thereby moving a sample by electrophoresis. The control program executes a first resistance value derivation process or a second resistance value derivation process to derive an electrical resistance value of a branch channel between the pair of channel ends before separating the sample. The first resistance value derivation process is a process of deriving an electrical resistance value based on a measured value obtained by applying an investigation voltage to the pair of channel ends, and the second resistance value derivation process is a process of deriving an electrical resistance value based on a measured value obtained by applying an investigation current to the pair of channel ends, and controls the voltage or current to be applied to the pair of channel ends based on the electrical resistance value derived by the first resistance value derivation process or the second resistance value derivation process.

[0012] According to the above aspects, the electrophoresis apparatus, the control method for the electrophoresis apparatus, and the control program for the electrophoresis apparatus of the present disclosure can suppress changes in electrophoresis conditions due to variations in the state of the reagent or between microchannels.

[0013] 1 is a schematic diagram showing an example of the configuration of a micro-channel chip according to an exemplary embodiment; FIG. 2 is a configuration diagram showing an example of the configuration of an electrophoresis device according to an exemplary embodiment; FIG. 3 is a schematic diagram showing an example of a micro-channel chip according to an exemplary embodiment; FIG. 4 is a block diagram showing an example of the hardware configuration of a control device according to an exemplary embodiment; FIG. 5 is a functional block diagram showing an example of the configuration of a control device according to an exemplary embodiment; FIG. 6 is a diagram explaining a specific example of a micro-channel chip; FIG. 7 is an example of an electrophoresis waveform when measuring alpha-fetoprotein, a tumor marker; FIG. 8 is a flowchart showing an example of control processing executed by a processor according to an exemplary embodiment; FIG. 9 is a diagram for explaining symbols used in the exemplary embodiment; FIG. 10 is a flowchart showing an example of resistance value derivation processing according to a first exemplary embodiment; FIG. 11 is a flowchart showing an example of capillary electrophoresis applied value derivation processing; FIG. 12 is a flowchart showing an example of capillary electrophoresis control processing; FIG. 13 is a flowchart showing an example of resistance value derivation processing according to a second exemplary embodiment; FIG. 14 is a schematic diagram showing another example of a micro-channel chip;

[0014] Hereinafter, examples of embodiments for carrying out the technology of the present disclosure will be described in detail with reference to the drawings.

[0015] First, a sample measurement method using an electrophoresis apparatus according to this exemplary embodiment using a micro-channel chip will be described, in which a tumor marker is used as an example of the sample.

[0016] FIG. 1 shows a schematic diagram of channels in a microchannel chip 20 according to this exemplary embodiment.

[0017] As shown in FIG. 1, the microchannel chip 20 of this exemplary embodiment includes a channel end 22 １ ~22 ６ and the flow path end 23 １ ~23 ４ The flow path end 22 １~22 ６ and the flow path end 23 １ ~23 ４ A branch flow path is connected to each of the main flow paths 28. ０ The flow path end 22 is connected to １ ~22 ６ is a reagent introduction section for introducing a reagent. １ ~22 ６ When referring to these collectively without distinguishing between them, the reference numerals 1 to 6 used to distinguish between them will be omitted and they will be referred to collectively as "flow path ends 22."

[0018] Flow path end 22 １ , 22 ２ , 22 ３ is a portion for introducing a buffer solution for electrophoresis. ４ is a site for introducing a first labeled antibody solution (for example, a solution containing a DNA-labeled tumor marker antibody). ５ , 22 ６ is a site for introducing an immune reaction solution between the tumor marker sample and a second labeled antibody solution (for example, a solution containing a fluorescently labeled antibody for the tumor marker).

[0019] Flow path end 22 １ ~22 ６ In this exemplary embodiment, a portion of the flow path end 22 １ ~22 ３ ) are provided with electrodes (not shown). １ , 22 ２ A cathode is disposed at the end of the flow path 22 ３ An anode is disposed in the main flow path 28. ０ and the flow path end 22 １ branch flow path 28 connected to １ and the flow path end 22 ２ branch flow path 28 connected to １３ and the flow path end 22 ３ branch flow path 28 connected to ９ As a result, a migration channel is formed.

[0020] Main channel 28 ０ , branch flow path 28 １ , and branch flow path 28９ through the flow path end 22 １ and the flow path end 22 ３ The branch flow path 28 is connected to the １３ and branch flow path 28 ９ through the flow path end 22 ２ and the flow path end 22 ３ The flow path end 22 is connected to the ４ ~22 ６ are connected to the main flow path 28 via the branch flow paths. ０ The main flow path 28 is connected to the ０ The flow path end 22 １ The side is referred to as the "upstream side", and the flow path end 22 ３ For example, from the upstream side to the downstream side, ４ , flow path end 22 ５ , flow path end 22 ６ , and the flow channel end 22 ２ are arranged in the order of:

[0021] On the other hand, the flow path end 23 １ ~23 ４ is a waste liquid storage section for storing waste liquid. １ ~23 ４ When referring to these collectively without distinguishing between them, the reference numerals 1 to 4 for distinguishing between them will be omitted and they will be referred to collectively as "flow path ends 23."

[0022] Flow path end 23 １ is the flow path end 22 １ The excess of the buffer solution introduced from the end of the flow channel 22 ４ This is a portion (waste reservoir) for storing the excess of the first labeled antibody solution introduced from the flow channel end 23. ２ is the flow path end 22 ４ The excess of the first labeled antibody solution introduced from the end of the flow channel 22 ５ This is a portion (waste reservoir) for storing the surplus immune reaction solution introduced from the flow channel end 23. ３ is the flow path end 22 ５ , 22 ６ The channel end 23 is a portion (waste reservoir) for storing the surplus of the immune reaction solution introduced from each of the channels. ４ is the flow path end 22 ６The excess of the immune reaction solution introduced from the flow channel end 22 ２ , 22 ３ This is a portion (waste reservoir) for storing the excess of the buffer solution introduced from the

[0023] Flow path end 23 １ ~23 ４ are connected to the main flow path 28 via the branch flow paths, respectively. ０ These are connected to the flow path end 23 from the upstream side to the downstream side. １ , 23 ２ , 23 ３ , 23 ４ More specifically, the flow path end 23 １ is the flow path end 22 １ downstream of the flow path end 22 ４ The flow path end 23 is located upstream of the flow path end 23. ２ is the flow path end 22 ４ downstream of the flow path end 22 ５ The flow path end 23 is located upstream of the flow path end 23. ３ is the flow path end 22 ５ downstream of the flow path end 22 ６ The flow path end 23 is located upstream of the flow path end 23. ４ is the flow path end 22 ６ downstream of the flow path end 22 ２ It is connected upstream of

[0024] The migration channel of this exemplary embodiment has, from upstream to downstream, a sample concentration region 30 and a sample separation region 32. A buffer solution for electrophoresis is introduced upstream of the sample concentration region 30. The sample concentration region 30 is a region in which a tumor marker, which is a sample, is concentrated using immune reaction and isotachophoresis (ITP). In the example shown in FIG. 1, the main channel 28 ０ and the flow path end 23 ２ From the branch point of the main flow path 28 ０ and the flow path end 22 ２ When performing isotachophoresis, the flow channel end 22 １ and the flow path end 22 ３The sample separation region 32 is a region where the tumor marker, which is a sample, is separated from other components by using capillary electrophoresis (CE), more specifically, capillary zone electrophoresis (CZE). ２ from the flow path end 22 ３ When capillary zone electrophoresis is performed, the flow channel end 22 ２ and the flow path end 22 ３ A voltage is applied between

[0025] The sample separation region 32 also includes a detection region 34 provided downstream for detecting the sample that has migrated through the migration channel.

[0026] In the microchannel chip 20 having the above configuration, the tumor marker sample can be analyzed as follows. １ and the flow path end 22 ３ When a voltage is applied between the end 22 of the flow channel, the flow path 22 moves in accordance with the principle of isotachophoresis. ４ The first labeled antibody (DNA-labeled tumor marker antibody) introduced from the main channel 28 ０ at the flow channel end 22 ３ In the sample concentration region 30, the first labeled antibody is concentrated, and an immune complex is formed between the tumor marker, the first labeled antibody, and the second labeled antibody (fluorescently labeled antibody for the tumor marker), forming a concentrated layer of the sample. ３ and reaches the sample separation region 32. Note that the unreacted (free) second labeled antibody does not have an electric charge in its molecule, so it remains at that position and does not reach the sample separation region 32.

[0027] When the immune complex of the tumor marker, the first labeled antibody, and the second labeled antibody reaches the sample separation region 32, more precisely, the branched flow path 28 １３ At the moment when the electrode reaches a position slightly downstream of the branch point 29, the electrode is switched, and the flow path end 22 ２ and the flow path end 22 ３In the sample separation region 32, the immune complex and the unreacted (free) first labeled antibody move at respective migration speeds according to the charge and molecular size between the flow channel end 22 and the sample separation region 32. ３ The tumor marker moves in the direction of the fluorescent dye. The concentration of the tumor marker can be measured from the peak area of ​​the fluorescence intensity when the immune complex containing the second labeled antibody with a tumor marker as its core and a fluorescent dye reaches the detection area 34. Note that the unreacted first labeled antibody does not have a fluorescent dye in its molecule, so even if it reaches the detection area 34, it does not affect the fluorescence intensity and does not affect the measurement of the tumor marker concentration.

[0028] [First Exemplary Embodiment] The configuration of an electrophoresis apparatus 1 according to this exemplary embodiment will be described with reference to Fig. 2. As shown in Fig. 2, the electrophoresis apparatus 1 includes a control device 10, a power supply device 12, a detection device 14, and a micro-channel chip 20. The micro-channel chip 20 shown in Figs. 2 and 3 has three channel ends 25 (first channel end 25), which are used when applying voltage in isotachophoresis and capillary electrophoresis. １ ~Third flow path end 25 ３ ) is provided. １ The first branch flow path 24 connected to １ and the second flow path end 25 ２ The second branch flow path 24 connected to ２ and the third flow path end 25 ３ The third branch flow path 24 connected to ３ The first branch flow path 24 is connected to the second branch flow path 24 by a branch point 26. １ The third branch channel 24 is provided with the sample concentration region 30 described above and is used as a channel for sample concentration. ３ The sample separation region 32 and the detection region 34 are provided in the sample separation region 32 and the detection region 34, and are used as a flow path for sample separation and a flow path for sample detection.

[0029] The power supply device 12 is controlled by the control device 10 to supply power to the first flow path end 25 １ ~Third flow path end 25 ３ Specifically, the power supply device 12 is a power supply for applying a voltage to each of the first flow path end 25. １ ~Third flow path end 25３ In this exemplary embodiment, however, it is simply said that "a voltage is applied to the flow path end 25", etc.

[0030] The detection device 14 includes a sensor 15. The sensor 15 is used to measure the concentration of a tumor marker and is a sensor for optically detecting an immune complex. ３ The detector 14 is disposed at a position facing the detection point 27 within the detection region 34 in the image sensor 10. The sensor 15 includes, for example, an LD (Laser Diode) or an LED (Light-Emitting Diode) that irradiates excitation light. In this case, the fluorescence generated by excitation with the excitation light irradiated from the sensor 15 is received by a photodetector such as a PD (Photodiode) or a PMT (Photomultiplier Tube). The detector 14 outputs a detection signal corresponding to the received fluorescence as the detection result of the sensor 15 to the control device 10.

[0031] The control device 10 has a function of performing overall control related to electrophoresis. Specifically, the control device 10 controls the electrodes that apply voltage to the power supply device 12, and controls the magnitude of the voltage or current to be applied, based on a detection signal input from the detection device 14.

[0032] Fig. 4 is a block diagram showing an example of the hardware configuration of the control device 10. As shown in Fig. 4, the control device 10 includes a processor 40 such as a CPU (Central Processing Unit), a memory 42, an I / F (Interface) unit 43, a storage unit 44, a display 46, and an input device 48. The processor 40, the memory 42, the I / F unit 43, the storage unit 44, the display 46, and the input device 48 are connected via a bus 49 such as a system bus or a control bus so as to be able to exchange various information with each other.

[0033] The processor 40 reads various programs, including the control program 45, stored in the storage unit 44 into the memory 42 and executes processing in accordance with the read programs. In this way, the processor 40 controls electrophoresis. The memory 42 is a work memory for the processor 40 to execute processing.

[0034] The control program 45 executed by the processor 40 is stored in the storage unit 44. Specific examples of the storage unit 44 include a hard disk drive (HDD) and a solid state drive (SSD).

[0035] The I / F unit 43 communicates various information with the power supply device 12 and the detection device 14 via wireless or wired communication. The display 46 and the input device 48 function as a user interface. The display 46 provides the user with various information related to sample analysis. The display 46 is not particularly limited, and examples thereof include an LCD monitor and an LED (Light Emitting Diode) monitor. The input device 48 is operated by the user to input various instructions related to the projection of the projected image. The input device 48 is not particularly limited, and examples thereof include a keyboard, a touch pen, and a mouse. The control device 10 employs a touch panel display that integrates the display 46 and the input device 48.

[0036] 5 is a functional block diagram illustrating an example of a configuration related to the functions of the control device 10 of this exemplary embodiment. As shown in FIG. 5, the control device 10 includes a resistance value deriving unit 50, a capillary electrophoresis applied value deriving unit 52, and a measurement control unit 54. As an example, in the control device 10 of this exemplary embodiment, the processor 40 executes a control program 45 stored in the storage unit 44, so that the processor 40 functions as the resistance value deriving unit 50, the capillary electrophoresis applied value deriving unit 52, and the measurement control unit 54.

[0037] The resistance value deriving unit 50 has a function of executing a process of deriving an electrical resistance value (hereinafter simply referred to as "resistance value") of the branch flow path 24 between a desired pair of flow path ends 25 before separating the sample. As an example, the resistance value deriving unit 50 of this exemplary embodiment derives the electrical resistance value of the pair of flow path ends 25 (second flow path end 25 ２ , third flow path end 25 ３ ) the second branch flow path 24 ２ , and the third branch flow path 24 ３ The resistance value deriving unit 50 outputs the derived resistance values ​​to the capillary electrophoresis applied value deriving unit 52.

[0038] As an example, in the case of a constant voltage load method, the resistance value derivation unit 50 of this exemplary embodiment is ２ , third flow path end 25 ３ ) is applied with a voltage for investigation, and the application of the voltage causes a pair of flow path ends 25 (second flow path ends 25 ２ , third flow path end 25 ３ The resistance value deriving unit 50 obtains, as measured values, a measured current value of the current flowing between the first branch flow path 24 and the second branch flow path 24, and a measured voltage value that is a voltage generated at the branch point 26 by the application of the applied voltage. ２ and the third branch flow path 24 ３ On the other hand, in the case of the constant current load method, the resistance value deriving unit 50 derives the resistance values ​​of the pair of flow path ends 25 (the second flow path end 25 ２ , third flow path end 25 ３ ) for the purpose of investigation, and the application of the current causes the pair of flow path ends 25 (second flow path ends 25 ２ , third flow path end 25 ３ ) and the voltage generated at the branch point 26 due to the application of the applied current. The resistance value deriving unit 50 then derives the resistance of the second branch flow path 24 based on the applied current value for investigation, the measured voltage value, and the measured voltage value at the branch point 26. ２ and the third branch flow path 24 ３ Derive the respective resistance values.

[0039] The magnitude of the voltage applied for investigation (hereinafter referred to as "investigation voltage") and the current applied for investigation (hereinafter referred to as "investigation current") are such that they do not affect the actual measurement, and their application time is such that they do not affect the actual measurement. "Not affecting the actual measurement" means that the movement of the sample caused by the application of the investigation voltage and investigation current is small enough to be negligible in the actual measurement, and the Joule heat generated by the application of the investigation voltage or investigation current is small enough not to affect the sample.

[0040] A specific example of the probe voltage and probe current will be described using the micro-channel chip 20 having the dimensions shown in FIG. １ ~Third branch flow path 24 ３ The width of each branch flow path 24 is 40 μm to 80 μm (however, the width of the first branch flow path 24 is 40 μm to 80 μm). １ The width of the hatched portion of the channel is 150 μm, and the height of the channel is 30 μm.

[0041] When performing isotachophoresis, the first flow path end 25 １ and the third flow path end 25 ３ A voltage of 4000 V is applied between the second flow path end 25 and the second flow path end 26 for about 50 to 100 seconds. ２ and the third flow path end 25 ３ A voltage of 1000V to 2000V is applied between the electrodes for approximately 20 to 50 seconds. Note that these specific values ​​are merely examples and will vary depending on the device, measurement items, etc.

[0042] FIG. 7 shows the electrophoretic waveform when α-fetoprotein, a tumor marker, was measured as a sample.

[0043] Second flow path end 25 ２ and the third flow path end 25 ３When a voltage of up to 1000 V is applied between the branch point 26 and the detection point 27, the sample moves between the branch point 26 and the detection point 27 (distance: 25 mm) in about 50 seconds. The electric field strength E, sample movement speed v, and sample electrophoretic mobility μ are as follows: Electric field strength E = 20 V / mm Sample movement speed v = 0.5 mm / s Sample electrophoretic mobility μ = 0.025 mm ２ 7, the time difference between peaks is at least 1 second, and a peak shift of 0.5 seconds affects the actual measurement. If the sample moving speed is 0.5 mm / s, a peak shift of 0.5 seconds corresponds to a distance shift of about 0.25 mm.

[0044] First, consider the effect of Joule heat per unit time generated by applying the probe voltage. Joule heat per unit time is proportional to the square of the voltage. Therefore, if the probe voltage is set to 10% or less of the voltage applied in capillary electrophoresis, the Joule heat per unit time generated by applying the probe voltage can be suppressed to 1% or less of the Joule heat per unit time generated during capillary electrophoresis, making the effect on actual measurement negligible.

[0045] Furthermore, consider the distance the sample moves when the probe voltage is 100 V (10% of the voltage applied in capillary electrophoresis). In this case, the sample movement speed is 0.05 mm / s. If the probe voltage is applied for 5 seconds or less (10% of the application time in capillary electrophoresis), the sample movement distance will be 0.25 mm or less, and the effect on the actual measurement can be negligibly small.

[0046] Therefore, the magnitude of the probe voltage or probe current is preferably 10% or less of the voltage or current applied in capillary electrophoresis, and the application time of the probe voltage or probe current is preferably 10% or less of the application time of the voltage or current applied in capillary electrophoresis.

[0047] The capillary electrophoresis applied value deriving unit 52 derives a pair of flow path ends 25 (second flow path end 25 ) based on the resistance value of the branch flow path 24 derived by the resistance value deriving unit 50 in order to perform capillary electrophoresis in actual measurement. ２ , third flow path end 25 ３ The capillary electrophoresis applied value deriving unit 52 outputs the derived voltage value or current value to the measurement control unit 54.

[0048] When performing capillary electrophoresis, the measurement control unit 54 controls the voltage or current value of the pair of flow path ends 25 (the second flow path end 25 ) based on the voltage value or current value derived by the capillary electrophoresis applied value deriving unit 52 . ２ , third flow path end 25 ３ ) to the power supply device 12.

[0049] Next, the operation of the control device 10 of this exemplary embodiment will be described. Fig. 8 shows a flowchart illustrating an example of the flow of control processing by the processor 40 of the control device 10 of this exemplary embodiment. As an example, when the processor 40 of this exemplary embodiment receives an instruction to start electrophoresis, it executes the control processing shown in Fig. 8.

[0050] In step S10 of FIG. 8, the resistance value derivation unit 50 performs a resistance value derivation process, the details of which will be described later, to determine the resistance value of the second branch flow path 24 as described above. ２ and the third branch flow path 24 ３ Derive the resistance value.

[0051] In the next step S12, the capillary electrophoresis applied value deriving unit 52 calculates the resistance value of the pair of flow path ends 25 (the second flow path end 25) based on the resistance value derived in step S10 by a capillary electrophoresis applied value deriving process, the details of which will be described later. ２ , third flow path end 25 ３ ) and derive the voltage value of the applied voltage or the current value of the applied current.

[0052] In the next step S14, the measurement control unit 54 determines whether or not to start actual measurement. Until actual measurement is started, the determination in step S14 remains negative. On the other hand, if actual measurement is to be started, the determination in step S14 remains positive, and the process proceeds to step S16.

[0053] In step S16, the measurement control unit 54 executes an isotachophoresis control process. In the isotachophoresis control process, the measurement control unit 54 controls the power supply device 12 to apply a predetermined voltage or current for isotachophoresis to the first flow path end 25. １ and the second flow path end 25 ２ By applying the voltage or current for isotachophoresis in this manner, the sample is concentrated as described above.

[0054] In the next step S18, the measurement control unit 54 performs capillary electrophoresis by applying the voltage or current calculated in step S12, as described above, through a capillary electrophoresis control process described in detail below, thereby separating the sample. When step S18 is completed, the control process shown in FIG. 8 is completed.

[0055] Next, the details of the resistance value derivation process in step S10, the capillary electrophoresis applied value derivation process in step S12, and the capillary electrophoresis control process in step S18 of the control process will be described. Note that, in the following, symbols and signs are used as shown in FIG. 9. For example, if the set value (known) of X (X=V, I) is X － and the measured value or control value (value known by measurement) of X (X=V, I) is represented as X^.

[0056] First, the resistance value derivation process in step S10 of the control process will be described. Fig. 10 shows a flowchart of an example of the resistance value derivation process in this exemplary embodiment.

[0057] In step S100 of Fig. 10, the resistance value derivation unit 50 determines whether the constant voltage load method is selected. In this exemplary embodiment, as described above, there are two types of load methods: a constant voltage load method in which an inspection voltage is applied, and a constant current load method in which an inspection current is applied. Which method is selected may be determined in advance, or may be switched in response to a user instruction. If the constant voltage load method is selected, the determination in step S100 is affirmative, and the process proceeds to step S102.

[0058] In step S102, the resistance value deriving unit 50 controls the power supply device 12 to １ Current value I of (first branch flow path) － ＣＨ１ This controls the first flow path end 25 １ Voltage value V^ １ and the voltage value V^ at the branch point 26 ｎｏｄｅ１ and become equal.

[0059] In the next step S104, the resistance value deriving unit 50 ２ and the third flow path end 25 ３ The voltage V － ２－３ (=V － ２ -V － ３ ) is applied.

[0060] In the next step S106, the resistance value deriving unit 50 controls the second flow path end 25 ２ and the third flow path end 25 ３ The current value I^ between ２－３ (=I^ ＣＨ２ =I^ ＣＨ３ ) is measured. That is, the investigation voltage V － ２－３ The current value I^ of the current that flows when ２－３ Measure.

[0061] In the next step S108, the resistance value deriving unit 50 calculates the resistance value of the second branch flow path 24 ２ and the third branch flow path 24 ３ , and calculate the resistance value of each of the second branch flow path 24. ２ Resistance value R ＣＨ２ is derived from the following equation (1), and the third branch flow path 24３ Resistance value R ＣＨ３ is derived from the following equation (2): In the following equations (1) and (2), the direction of current flow in which positive charges flow is considered positive, and the resistance value is not negative.

[0062] When the process of step S108 is completed, the resistance value derivation process shown in FIG. 10 is completed.

[0063] On the other hand, in the case of the constant current load method, the determination in step S100 is negative, and the process proceeds to step S110.

[0064] In step S110, the resistance value deriving unit 50, similarly to step S102, controls the power supply device 12 to １ Current value I of (first branch flow path) － ＣＨ１ This controls the first flow path end 25 １ Voltage value V^ １ and the voltage value V^ at the branch point 26 ｎｏｄｅ１ and become equal.

[0065] In the next step S112, the resistance value deriving unit 50 ２ and the third flow path end 25 ３ The investigation current I － ２－３ (=I － ＣＨ２ =I － ＣＨ３ ) is applied.

[0066] In the next step S114, the resistance value deriving unit 50 controls the second flow path end 25 ２ and the third flow path end 25 ３ The voltage value V^ of the voltage generated between ２－３ That is, the investigation current I － ２－３ The voltage value V^ of the voltage generated by applying ２－３ Measure.

[0067] In the next step S116, the resistance value deriving unit 50 calculates the resistance value of the second branch flow path 24 ２ and the third branch flow path 24 ３ , and calculate the resistance value of each of the second branch flow path 24. ２Resistance value R ＣＨ２ is derived from the following equation (3), and the third branch flow path 24 ３ Resistance value R ＣＨ３ is derived from the following formula (4). ３ Voltage value V － ３ In the case of the constant current load method, the potential cannot be uniquely determined unless one of the potentials is set. Therefore, as shown in the following equation (4), the voltage value V － ３ is a known value as a set value. ２ Voltage value V － ２ may be set as a set value (known value).

[0068]

[0069] When the process of step S116 is completed, the resistance value derivation process shown in FIG. 10 is completed.

[0070] In this way, the resistance value derivation process shown in FIG. 10 ２ and the third branch flow path 24 ３ Derive the resistance value.

[0071] Next, the capillary electrophoresis application value derivation process in step S12 of the control process will be described. Fig. 11 shows a flowchart of an example of the capillary electrophoresis application value derivation process of this exemplary embodiment.

[0072] In step S130 of FIG. 11, the capillary electrophoresis applied value deriving unit 52 determines whether the second flow path end 25 ２ and the third flow path end 25 ３ If the controlled object is a voltage, in other words, the second flow path end 25 ２ and the third flow path end 25 ３ When controlling the voltage applied between the first and second electrodes, the determination in step S130 becomes affirmative, and the process proceeds to step S132.

[0073] In step S132, the capillary electrophoresis applied value deriving unit 52 determines whether the control target to be controlled to a desired value is voltage (voltage value). In this exemplary embodiment, the control target is voltage or power. If voltage is to be controlled, the determination in step S132 is affirmative, and the process proceeds to step S134.

[0074] In step S134, the capillary electrophoresis applied value deriving unit 52 determines whether the third branch flow path 24 ３ Voltage V － ＣＨ３ From the set value (desired value) of the second flow path end 25 ２ and the third flow path end 25 ３ The voltage value V applied between ２－３ is derived using the following equation (5).

[0075] When the process of step S134 is completed, the capillary electrophoresis applied value derivation process shown in FIG. 11 is completed.

[0076] On the other hand, in step S132, if the control target to be set as the desired value is power (power value), the determination in step S132 becomes negative, and the process proceeds to step S136. ３ Power P － Ｃ Ｈ３ From the set value (desired value) of the second flow path end 25 ２ and the third flow path end 25 ３ The voltage value V applied between ２－３ is derived using the following equation (6).

[0077] When the process of step S136 is completed, the capillary electrophoresis application value derivation process shown in FIG. 11 is completed.

[0078] In step S130, the second flow path end 25 ２ and the third flow path end 25 ３ The control target applied between the second flow path end 25 is not a voltage. ２ and the third flow path end 25 ３When controlling the current to be applied between the first and second electrodes, the determination in step S130 becomes negative, and the process proceeds to step S138.

[0079] In step S138, the capillary electrophoresis applied value deriving unit 52 determines whether the control target to be controlled to a desired value is voltage (voltage value), as in step S132. If voltage is to be controlled, the determination in step S138 is affirmative, and the process proceeds to step S140.

[0080] In step S140, the capillary electrophoresis applied value deriving unit 52 determines whether the third branch flow path 24 ３ Voltage V － ＣＨ３ From the set value (desired value) of the second flow path end 25 ２ and the third flow path end 25 ３ The current value I of the applied current applied between ２－３ is derived using the following equation (7).

[0081] When the process of step S140 is completed, the capillary electrophoresis application value derivation process shown in FIG. 11 is completed.

[0082] On the other hand, in step S138, if the control target to be set as the desired value is power (power value), the determination in step S138 becomes negative, and the process proceeds to step S142. ３ Power P － ＣＨ３ From the set value (desired value) of the second flow path end 25 ２ and the third flow path end 25 ３ The current value I of the applied current applied between ２－３ is derived using the following equation (8).

[0083] When the process of step S142 is completed, the capillary electrophoresis application value derivation process shown in FIG. 11 is completed.

[0084] In this way, by the capillary electrophoresis applied value derivation process shown in FIG. 11, the second flow path end 25 ２ and the third flow path end 25 ３The voltage value of the voltage applied between the two electrodes or the current value of the current applied between the two electrodes can be derived.

[0085] Next, the capillary electrophoresis control process in step S18 of the control process described above will be described. Fig. 12 shows a flowchart of an example of the capillary electrophoresis control process of this exemplary embodiment.

[0086] In step S160 of Fig. 12, the measurement control unit 54 determines whether or not to control the applied voltage. If the applied voltage is to be controlled, the determination in step S160 becomes positive, and the process proceeds to step S162. In step S162, the measurement control unit 54 determines the voltage value V of the applied voltage derived by the capillary electrophoresis applied voltage derivation process (see Fig. 11) described above. ２－３ the second flow path end 25 ２ and the third flow path end 25 ３ When the process of step S162 is completed, the capillary electrophoresis control process shown in FIG.

[0087] On the other hand, if the applied voltage is not controlled, in other words, if the applied current is controlled, the determination in step S160 becomes negative, and the process proceeds to step S164. In step S164, the measurement control unit 54 calculates the applied current value I ２－３ The second flow path end 25 ２ and the third flow path end 25 ３ When the process of step S164 is completed, the capillary electrophoresis control process shown in FIG.

[0088] In this manner, the control device 10 of the electrophoresis device 1 of this exemplary embodiment controls the second flow path end 25 to which the applied voltage or current is applied in capillary electrophoresis. ２ and the third flow path end 25 ３ The second branch flow path 24 is a flow path between ２ and the third branch flow path 24 ３ Resistance value R ＣＨ２ , R ＣＨ３ As a result, the control device 10 can derive the derived resistance value R ＣＨ２ , R ＣＨ３Based on this, a pair of flow path ends 25 (second flow path ends 25 ２ , third flow path end 25 ３ ) the voltage value V ２－３ Or the current value I of the applied current ２－３ can be derived.

[0089] Second Exemplary Embodiment In this exemplary embodiment, another form of the resistance value derivation process (see FIG. 10 ) described above will be described. Note that the configuration of the control device 10 is the same as that of the first exemplary embodiment, and therefore description thereof will be omitted.

[0090] In the resistance value derivation process of the first exemplary embodiment, the potential V ｎｏｄｅ１ However, in this exemplary embodiment, the potential V of the branch point 26 is monitored. ｎｏｄｅ１ There is no monitoring of the

[0091] 13 shows a flowchart of an example of the resistance value derivation process of this exemplary embodiment. In step S200 of FIG. 13, the resistance value derivation unit 50 determines whether the constant voltage load method is used, similar to step S100 of the resistance value derivation process of the first exemplary embodiment (see FIG. 10). If the constant voltage load method is used, the determination in step S200 is affirmative, and the process proceeds to step S202.

[0092] In step S202, the resistance value deriving unit 50 ２ and the third flow path end 25 ３ The voltage V － ２－３ (=V － ２ -V － ３ ) is applied to the first flow path end 25 １ be disconnected from the power supply.

[0093] In the next step S204, the resistance value deriving unit 50 controls the second flow path end 25 ２ and the third flow path end 25 ３ The current value I^ between ２－３ (=I^ ＣＨ２ =I^ ＣＨ３ ) is measured. That is, the investigation voltage V － ２－３The current value I^ of the current that flows when ２－３ Measure.

[0094] In the next step S206, the resistance value deriving unit 50 ３ and the first flow path end 25 １ The voltage V － ３－１ (=V － ３ -V － １ ) is applied to the second flow path end 25 ２ be disconnected from the power supply.

[0095] In the next step S208, the resistance value deriving unit 50 controls the third flow path end 25 ３ and the first flow path end 25 １ The current value I^ between ３－１ (=I^ ＣＨ３ =I^ ＣＨ１ ) is measured. That is, the investigation voltage V － ３－１ The current value I^ of the current that flows when ３－１ Measure.

[0096] In the next step S210, the resistance value deriving unit 50 １ and the second flow path end 25 ２ The voltage V － １－２ (=V － １ -V － ２ ) is applied to the third flow path end 25 ３ be disconnected from the power supply.

[0097] In the next step S212, the resistance value deriving unit 50 controls the first flow path end 25 １ and the second flow path end 25 ２ The current value I^ between １－２ (=I^ ＣＨ１ =I^ ＣＨ２ ) is measured. That is, the investigation voltage V － １－２ The current value I^ of the current that flows when １－２ Measure.

[0098] In the next step S214, the resistance value derivation unit 50 calculates the resistance value of the first branch flow path 24 by solving the simultaneous equations (9) below. １ Resistance value R ＣＨ１ , second branch flow path 24 ２ Resistance value R ＣＨ２ , and the third branch flow path 24 ３ Resistance value R ＣＨ３ The resistance value R ＣＨ１ , resistance value R ＣＨ２ , and resistance value R ＣＨ３ Since all the values ​​other than are known, the simultaneous equations (9) below can be solved. In addition, the second branch flow path 24 ２ Resistance value R ＣＨ２ , and the third branch flow path 24 ３ Resistance value R ＣＨ３ When the process of step S214 ends, the resistance value derivation process shown in FIG.

[0099] On the other hand, in the case of the constant current load method, the determination in step S200 is negative, and the process proceeds to step S216.

[0100] In step S216, the resistance value deriving unit 50 ２ and the third flow path end 25 ３ The investigation current I － ２－３ is applied to the first flow path end 25 １ be disconnected from the power supply.

[0101] In the next step S218, the resistance value deriving unit 50 controls the second flow path end 25 ２ and the third flow path end 25 ３ The voltage value V^ of the voltage generated between ２－３ (=V^ ２ -V^ ３ ) is measured. That is, the investigation current I － ２－３ The voltage V^ generated by applying ２－３ Measure.

[0102] In the next step S220, the resistance value deriving unit 50 ３ and the first flow path end 25 １ The investigation current I－ ３－１ The second flow path end 25 ２ be disconnected from the power supply.

[0103] In the next step S222, the resistance value deriving unit 50 controls the third flow path end 25 ３ and the first flow path end 25 １ The voltage value V^ of the voltage generated between ３－１ (=V^ ３ -V^ １ ) is measured. That is, the investigation current I － ３－１ The voltage V^ generated by applying ３－１ Measure.

[0104] In the next step S224, the resistance value deriving unit 50 １ and the second flow path end 25 ２ The investigation current I － １－２ The third flow path end 25 ３ be disconnected from the power supply.

[0105] In the next step S226, the resistance value deriving unit 50 controls the first flow path end 25 １ and the second flow path end 25 ２ The voltage value V^ of the voltage generated between １－２ (=V^ １ -V^ ２ ) is measured. That is, the investigation current I － １－２ The voltage V^ generated by applying １－２ Measure.

[0106] In the next step S228, the resistance value derivation unit 50 calculates the resistance value of the first branch flow path 24 by solving the simultaneous equations (10) below. １ Resistance value R ＣＨ１ , second branch flow path 24 ２ Resistance value R ＣＨ２ , and the third branch flow path 24 ３ Resistance value R ＣＨ３ The resistance value R ＣＨ１ , resistance value R ＣＨ２ , and resistance value R ＣＨ３Since all the values ​​other than are known, the simultaneous equations (10) below can be solved. In addition, the second branch flow path 24 ２ Resistance value R ＣＨ２ , and the third branch flow path 24 ３ Resistance value R ＣＨ３ When the process of step S228 ends, the resistance value derivation process shown in FIG.

[0107] In this way, in the control device 10 of this exemplary embodiment, the second branch flow path 24 ２ Resistance value R ＣＨ２ , and the third branch flow path 24 ３ Resistance value R ＣＨ３ Therefore, the pair of flow path ends 25 (second flow path end 25 ２ , third flow path end 25 ３ ) the voltage value V ２－３ Or the current value I of the applied current ２－３ can be derived.

[0108] As described above, the control device 10 of the electrophoresis device 1 of each of the above embodiments controls the pair of flow path ends 25 (second flow path ends 25 ２ , third flow path end 25 ３ ) second branch flow path 24 ２ and the third branch flow path 24 ３ The resistance value derivation process is performed to derive the electrical resistance value of the second branch flow path 24. ２ Resistance value R ＣＨ２ , and the third branch flow path 24 ３ Resistance value R ＣＨ３ The control device 10 also derives the derived resistance value R ＣＨ２ and resistance value R ＣＨ３ Based on this, a pair of flow path ends 25 (second flow path ends 25 ２ , third flow path end 25 ３ ) the voltage value V ２－３ Or the current value I of the applied current ２－３ The control device 10 can derive the derived voltage value V ２－３ Or the current value I of the applied current ２－３ is the second flow path end 25 ２ and the third flow path end 25 ３The power supply 12 is controlled so that the voltage is applied between the

[0109] Therefore, according to the control device 10 of each of the above forms, even if the electrical resistance value of the branch channel 24 changes due to variations in the reagent state or between the microchannels, changes in the electrophoresis conditions can be suppressed.

[0110] The microchannel chip 20 is not limited to the microchannel chip 20 shown in the first and second exemplary embodiments. The microchannel chip 20 may be any microchannel chip that includes three or more channel ends, one or more branch points, and a plurality of branch channels branched by the branch points and connected to the respective channel ends, and in which a channel is formed in which a sample moves by electrophoresis when a voltage or current is applied to a pair of channel ends selected from the plurality of channel ends. For example, the microchannel chip 20 may have the form of the microchannel chip 20 shown in FIG. 1.

[0111] According to the present disclosure, the resistance value of the branch channel can be derived in the micro-channel chip 20 of other shapes, as long as the channel shape is chain-shaped, without being limited to the shape of the micro-channel chip 20 shown in Figures 1 and 3. For example, the resistance value of the branch channel can be derived in the micro-channel chip 20 shown in Figures 14 and 15. For example, in the micro-channel chip 20 shown in Figure 14 (similar to the micro-channel chip 20 in Figure 1), the resistance value of the branch channel 28 １ ~28 １７ Resistance value R １ ~R １７ In the first exemplary embodiment, the flow channel end 22 １ and the flow path end 22 ３ By applying an investigation voltage or investigation current between the branch flow path 28 and the branch flow path 29 and monitoring the potential at the other flow path ends 22 and 23, １ ~ Branch flow path 28 ９ Resistance value R １ ~R ９ In addition, the flow path end 22 ４ and the flow path end 23 １ By applying an investigation voltage or investigation current between the branch flow path 28 and the branch flow path 29 and monitoring the potential at the other flow path ends 22 and 23, １０ and branch flow path 28１４ Resistance value R １０ , R １４ In addition, the flow path end 22 ５ and the flow path end 23 ２ By applying an investigation voltage or investigation current between the branch flow path 28 and the branch flow path 29 and monitoring the potential at the other flow path ends 22 and 23, １１ and branch flow path 28 １５ Resistance value R １１ , R １５ In addition, the flow path end 22 ６ and the flow path end 23 ３ By applying an investigation voltage or investigation current between the branch flow path 28 and the branch flow path 29 and monitoring the potential at the other flow path ends 22 and 23, １２ and branch flow path 28 １６ Resistance value R １２ , R １６ In addition, the flow path end 22 ２ and the flow path end 23 ４ By applying an investigation voltage or investigation current between the branch flow path 28 and the branch flow path 29 and monitoring the potential at the other flow path ends 22 and 23, １３ and branch flow path 28 １７ Resistance value R １３ , R １７ can be derived.

[0112] On the other hand, in the second exemplary embodiment, the flow channel end 22 １ and the flow path end 22 ３ Between the flow path end 22 １ and the flow path end 22 ４ Between the flow path end 22 １ and the flow path end 22 ５ Between the flow path end 22 １ and the flow path end 22 ６ Between the flow path end 22 １ and the flow path end 22 ２ Between the flow path end 22 １ and the flow path end 23 １ Between the flow path end 22 １ and the flow path end 23 ２ Between the flow path end 22 １ and the flow path end 23 ３ Between the flow path end 22 １ and the flow path end 23 ４ Between the flow path end 22 ３and the flow path end 22 ４ Between the flow path end 22 ３ and the flow path end 22 ５ Between the flow path end 22 ３ and the flow path end 22 ６ Between the flow path end 22 ３ and the flow path end 22 ２ Between the flow path end 22 ３ and the flow path end 23 １ Between the flow path end 22 ３ and the flow path end 23 ２ Between the flow path end 22 ３ and the flow path end 23 ３ and the flow path end 22 ３ and the flow path end 23 ４ Seventeen simultaneous equations are obtained from measurements obtained by applying an investigation voltage or investigation current between the branch flow path 28 and the branch flow path 28. １ ~28 １７ Resistance value R １ ~R １７ can be derived.

[0113] In addition, for example, in the micro-channel chip 20 shown in FIG. １ ~28 １３ Resistance value R １ ~R １３ In the first exemplary embodiment, the flow channel end 22 １ and the flow path end 22 １０ By applying an investigation voltage or investigation current between the branch flow path 28 and the other flow path end 22 and monitoring the potential of the other flow path end 22, １ , branch flow path 28 ４ , branch flow path 28 ７ , branch flow path 28 １０ , branch flow path 28 １３ Resistance value R １ , R ４ , R ７ , R １０ , R １３ In addition, the flow path end 22 ２ and the flow path end 22 ３ By applying an investigation voltage or investigation current between the branch flow path 28 and the other flow path end 22 and monitoring the potential of the other flow path end 22, ２ and branch flow path 28 ３ Resistance value R２ , R ３ In addition, the flow path end 22 ４ and the flow path end 22 ５ By applying an investigation voltage or investigation current between the branch flow path 28 and the other flow path end 22 and monitoring the potential of the other flow path end 22, ５ and branch flow path 28 ６ Resistance value R ５ , R ６ In addition, the flow path end 22 ６ and the flow path end 22 ７ By applying an investigation voltage or investigation current between the branch flow path 28 and the other flow path end 22 and monitoring the potential of the other flow path end 22, ８ and branch flow path 28 ９ Resistance value R ８ , R ９ In addition, the flow path end 22 ８ and the flow path end 22 ９ By applying an investigation voltage or investigation current between the branch flow path 28 and the other flow path end 22 and monitoring the potential of the other flow path end 22, １１ and branch flow path 28 １２ Resistance value R １１ , R １２ can be derived.

[0114] On the other hand, in the second exemplary embodiment, the flow channel end 22 １ and the flow path end 22 ２ Between the flow path end 22 １ and the flow path end 22 ３ Between the flow path end 22 １ and the flow path end 22 ４ Between the flow path end 22 １ and the flow path end 22 ５ Between the flow path end 22 １ and the flow path end 22 ６ Between the flow path end 22 １ and the flow path end 22 ７ Between the flow path end 22 １ and the flow path end 22 ８ Between the flow path end 22 １ and the flow path end 22 ９ Between the flow path end 22 １ and the flow path end 22 １０ Between the flow path end 22 ２ and the flow path end 22 ３Between the flow path end 22 ４ and the flow path end 22 ５ Between the flow path end 22 ６ and the flow path end 22 ７ and the flow path end 22 ８ and the flow path end 22 ９ 13 simultaneous equations are obtained from measurements obtained by applying a test voltage or test current between the branch flow path 28 and the branch flow path 28. １ ~28 １３ Resistance value R １ ~R １３ can be derived.

[0115] 14 and 15 , the resistance value of the branch channel 28 can be derived, and therefore, from Ohm's law, the voltage to be applied between the pair of channel ends 22 can be derived using equations similar to the above equations (5) and (6). Furthermore, the current to be applied between the pair of channel ends 22 can be derived using equations similar to the above equations (7) and (8) obtained from Ohm's law. As a result, the voltage and power applied to the branch channel 28 between the pair of channel ends 22 can be controlled in the micro-channel chip 20 shown in FIGS. 14 and 15 .

[0116] In the above embodiment, the applied voltage or current for isotachophoresis is predetermined (predetermined value), but it may be derived based on the electrical resistance value of the channel, similar to the applied voltage or current for capillary electrophoresis. For example, in the case of the microchannel chip 20 shown in FIG. 3, the first branch channel 24 １ The resistance value of the first branch flow path 24 is calculated. １ Based on the resistance value of the first flow path end 25 １ and the third flow path end 25 ３ In this way, the voltage or current applied between the first branch channel 24 and the microchannel may be detected due to variations in the reagent state or variations between the microchannels. １ Even if the resistance value of the first flow path end 25 changes, １ and the third flow path end 25 ３ The voltage or current applied between the first branch flow path 24 １Therefore, it is possible to prevent the electrophoresis conditions for isotachophoresis from changing.

[0117] Furthermore, the detection device 14 is not limited to a form including the sensor 15 that optically detects immune complexes, and may be of a form appropriate for the sample, etc. For example, when magnetic particles are added to the sample instead of a fluorescent dye, the sensor 15 may be a sensor that magnetically detects immune complexes.

[0118] In each of the above embodiments, the following various processors can be used as the hardware structure of the processing units that execute various processes, such as the resistance value deriving unit 50, the capillary electrophoresis applied value deriving unit 52, and the measurement control unit 54. As described above, the various processors include a CPU, which is a general-purpose processor that executes software (programs) to function as various processing units, as well as dedicated electrical circuits that are processors having a circuit configuration specifically designed to execute specific processes, such as a programmable logic device (PLD) that is a processor whose circuit configuration can be changed after manufacture, such as an FPGA (Field Programmable Gate Array), and an ASIC (Application Specific Integrated Circuit).

[0119] A single processing unit may be configured with one of these various processors, or may be configured with a combination of two or more processors of the same or different types (for example, a combination of multiple FPGAs, or a combination of a CPU and an FPGA). Also, multiple processing units may be configured with a single processor.

[0120] Examples of configuring multiple processing units with a single processor include: first, a form in which one processor is configured with a combination of one or more CPUs and software, and this processor functions as multiple processing units, as typified by computers such as client and server; second, a form in which a processor is used to realize the functions of an entire system including multiple processing units with a single IC (Integrated Circuit) chip, as typified by systems on chips (SoCs); and thus, various processing units are configured using one or more of the above-mentioned various processors as a hardware structure.

[0121] Furthermore, more specifically, the hardware structure of these various processors can be an electric circuit that combines circuit elements such as semiconductor elements.

[0122] Furthermore, in the above exemplary embodiments, the control program 45 is described as being pre-stored (installed) in the storage unit 44, but this is not limiting. The control program 45 may be provided in a form recorded on a recording medium such as a CD-ROM (Compact Disc Read Only Memory), a DVD-ROM (Digital Versatile Disc Read Only Memory), or a USB (Universal Serial Bus) memory. The control program 45 may also be downloaded from an external device via a network. In other words, the program (program product) described in the exemplary embodiments may be provided on a recording medium or may be distributed from an external computer.

[0123] The following additional notes are provided regarding the above exemplary embodiments.

[0124] (Supplementary Note 1) An electrophoresis device for separating a sample using a micro-channel chip in which a channel is formed, the channel including three or more channel ends, one or more branch points, and a plurality of branch channel branches at the branch points and connected to each channel end, the channel through which the sample moves by electrophoresis when a voltage or current is applied to a pair of channel ends selected from the plurality of channel ends, the electrophoresis device comprising at least one processor, wherein the processor: before separating the sample, executes a first resistance value derivation process or a second resistance value derivation process for deriving an electrical resistance value of a branch channel between the pair of channel ends, the first resistance value derivation process is a process for deriving the electrical resistance value based on a measurement value obtained by applying an investigation voltage to the pair of channel ends, the second resistance value derivation process is a process for deriving the electrical resistance value based on a measurement value obtained by applying an investigation current to the pair of channel ends, and controls the voltage or current applied to the pair of channel ends based on the electrical resistance value derived by the first resistance value derivation process or the second resistance value derivation process.

[0125] (Supplementary Note 2) The electrophoresis device according to Supplementary Note 1, wherein the first resistance value derivation process is a process of applying an inspection applied voltage to the pair of flow path ends, acquiring as the measured values ​​a measured current value of a current flowing between the pair of flow path ends due to the application of the applied voltage, and a first measured voltage value which is a voltage generated at a branch point between the pair of flow path ends due to the application of the applied voltage, and deriving the electrical resistance value based on the inspection applied voltage value, the measured current value, and the first measured voltage value; and the second resistance value derivation process is a process of applying an inspection applied current to the pair of flow path ends, acquiring as the measured values ​​a second measured voltage value of a voltage generated between the pair of flow path ends due to the application of the applied current, and a third measured voltage value which is a voltage generated at a branch point between the pair of flow path ends due to the application of the applied current.

[0126] (Supplementary Note 3) The electrophoresis device according to Supplementary Note 1, wherein the first resistance value derivation process is a process of sequentially applying the inspection voltage to a plurality of pairs of flow path ends selected from the flow path ends, obtaining, as the measurement values, measured current values ​​of currents flowing in each of the plurality of pairs of flow path ends due to the application of the inspection voltage, and deriving the electrical resistance value based on the inspection inspection voltage value and the measured current value of each of the pair of flow path ends; and the second resistance value derivation process is a process of sequentially applying the inspection current to a plurality of pairs of flow path ends selected from the flow path ends, obtaining, as the measurement values, measured voltage values ​​of voltages generated in each of the plurality of pairs of flow path ends due to the application of the inspection current, and deriving the electrical resistance value based on the inspection inspection current value and the measured voltage value of each of the pair of flow path ends.

[0127] (Supplementary Note 4) The electrophoresis device according to any one of Supplementary Notes 1 to 3, wherein the applied voltage or current applied to the pair of flow path ends when separating the sample includes an applied voltage or current for isotachophoresis when the electrophoresis is used to move the sample, and an applied voltage or current for capillary electrophoresis when the electrophoresis is used to move the sample, and the applied voltage value or applied current value for investigation is 10% or less of the applied voltage value or applied current value for capillary electrophoresis.

[0128] (Supplementary Note 5) The electrophoresis device according to any one of Supplementary Notes 1 to 4, wherein the application time for applying a voltage or current to the pair of flow path ends when separating the sample includes an application time for isotachophoresis when the electrophoresis is used to move the sample by isotachophoresis, and an application time for capillary electrophoresis when the electrophoresis is used to move the sample by capillary electrophoresis, and the application time for applying the investigation voltage or investigation current is 10% or less of the application time for capillary electrophoresis.

[0129] (Supplementary Note 6) A method for controlling an electrophoresis device for separating a sample using a micro-channel chip in which a channel is formed, the channel including three or more channel ends, one or more branch points, and a plurality of branch channel branches at the branch points and connected to each channel end, the channel through which the sample moves by electrophoresis when a voltage or current is applied to a pair of channel ends selected from the plurality of channel ends, the electrophoresis device including a processor, the processor performing a first resistance value derivation process or a second resistance value derivation process for deriving an electrical resistance value of a branch channel between the pair of channel ends before separating the sample, the first resistance value derivation process being a process for deriving the electrical resistance value based on a measurement value obtained by applying an investigation voltage to the pair of channel ends, the second resistance value derivation process being a process for deriving the electrical resistance value based on a measurement value obtained by applying an investigation current to the pair of channel ends, and controlling the voltage or current applied to the pair of channel ends based on the electrical resistance value derived by the first resistance value derivation process or the second resistance value derivation process. A method for controlling an electrophoresis device.

[0130] (Supplementary Note 7) A control program for causing a computer to function as an electrophoresis device that separates a sample using a micro-channel chip in which a channel is formed, the channel including three or more channel ends, one or more branch points, and a plurality of branch channel branches at the branch points and connected to each channel end, the channel through which a sample moves by electrophoresis when a voltage or current is applied to a pair of channel ends selected from the plurality of channel ends, the control program for an electrophoresis device comprising: before separating the sample, executing a first resistance value derivation process or a second resistance value derivation process that derives an electrical resistance value of a branch channel between the pair of channel ends; the first resistance value derivation process is a process that derives the electrical resistance value based on a measured value obtained by applying an investigation voltage to the pair of channel ends; and the second resistance value derivation process is a process that derives the electrical resistance value based on a measured value obtained by applying an investigation current to the pair of channel ends; and controlling the voltage or current applied to the pair of channel ends based on the electrical resistance value derived by the first resistance value derivation process or the second resistance value derivation process.

[0131] The disclosure of Japanese Patent Application No. 2022-159107, filed September 30, 2022, is incorporated herein by reference in its entirety.

[0132] All publications, patent applications, and technical standards mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent application, or technical standard was specifically and individually indicated to be incorporated by reference.

Claims

1. A microchannel chip including three or more plurality of channel ends, one or more branch points, and a plurality of branched channels branched by the branch points and connected to each channel end, wherein a voltage or current is applied to a pair of channel ends selected from the plurality of channel ends to form a channel in which a sample moves by electrophoresis, and an electrophoresis apparatus for separating the sample using the microchannel chip, comprising at least one processor, wherein the processor performs a first resistance value derivation process or a second resistance value derivation process for deriving an electrical resistance value of a branched channel between the pair of channel ends before separating the sample, the first resistance value derivation process is a process of deriving the electrical resistance value based on a measured value obtained by applying an investigation application voltage to the pair of channel ends, the second resistance value derivation process is a process of deriving the electrical resistance value based on a measured value obtained by applying an investigation application current to the pair of channel ends, controls a voltage or current applied to the pair of channel ends based on the electrical resistance value derived by the first resistance value derivation process or the second resistance value derivation process Electrophoresis apparatus.

2. In the first resistance value derivation process, an investigation application voltage is applied to the pair of channel ends, and a measured current value of a current flowing between the pair of channel ends due to the application of the application voltage and a first measured voltage value which is a voltage generated at a branch point between the pair of channel ends due to the application of the application voltage are obtained as the measured values, and the electrical resistance value is derived based on the investigation application voltage value, the measured current value, and the first measured voltage value, in the second resistance value derivation process, an investigation application current is applied to the pair of channel ends, and a second measured voltage value of a voltage generated between the pair of channel ends due to the application of the application current and a third measured voltage value which is a voltage generated at a branch point between the pair of channel ends due to the application of the application current are obtained as the measured values, and the electrical resistance value is derived based on the investigation application current value, the second measured voltage value, and the third measured voltage value The electrophoresis apparatus according to claim 1.

3. In the first resistance value derivation process, the investigation application voltage is sequentially applied to a plurality of pairs of channel ends selected from the channel ends, and a measured current value of a current flowing through each of the plurality of pairs of channel ends due to the application of the application voltage is obtained as the measured value, A process of deriving the electrical resistance value based on the applied voltage value for investigation and the measured current value of each of the pair of flow path ends. In the second resistance value derivation process, an applied current for investigation is sequentially applied to a plurality of pairs of flow path ends selected from among the flow path ends. A measured voltage value of the voltage generated at each of the plurality of pairs of flow path ends due to the application of the applied current is acquired as the measured value. A process of deriving the electrical resistance value based on the applied current value for investigation and the measured voltage value of each of the pair of flow path ends. The electrophoresis apparatus according to claim 1.

4. When separating the sample, the applied voltage or applied current applied to the pair of flow path ends includes an applied voltage or applied current for isotachophoresis when moving the sample by isotachophoresis as the electrophoresis, and an applied voltage or applied current for capillary electrophoresis when moving the sample by capillary electrophoresis as the electrophoresis. The applied voltage value for investigation or the applied current value for investigation is 10% or less of the applied voltage value or applied current value for capillary electrophoresis. The electrophoresis apparatus according to claim 1.

5. When separating the sample, the application time of the applied voltage or applied current applied to the pair of flow path ends includes an application time for isotachophoresis when moving the sample by isotachophoresis as the electrophoresis, and an application time for capillary electrophoresis when moving the sample by capillary electrophoresis as the electrophoresis. The application time for applying the applied voltage for investigation or the applied current for investigation is 10% or less of the application time for capillary electrophoresis. The electrophoresis apparatus according to claim 1.

6. The first resistance value derivation process or the second resistance value derivation process is performed on the branch flow path between the pair of flow path ends used for separating the sample. Controlling the voltage or current applied to the pair of flow path ends is to control the voltage or current applied between the pair of flow path ends used for separating the sample when separating the sample, based on the derived electrical resistance value of the branch flow path. The electrophoresis apparatus according to claim 1.

7. A control method for an electrophoresis apparatus that separates a sample using a microchannel chip including three or more flow channel ends, one or more branch points, and a plurality of branch channels branched by the branch points and connected to each flow channel end, wherein a channel is formed in which the sample moves by electrophoresis when a voltage or current is applied to a pair of flow channel ends selected from the plurality of flow channel ends, comprising: The electrophoresis apparatus includes a processor, The processor, Before separating the sample, execute a first resistance value derivation process or a second resistance value derivation process for deriving the electrical resistance value of the branch channel between the pair of flow channel ends, The first resistance value derivation process is a process of deriving the electrical resistance value based on a measurement value obtained by applying an investigation application voltage to the pair of flow channel ends, The second resistance value derivation process is a process of deriving the electrical resistance value based on a measurement value obtained by applying an investigation application current to the pair of flow channel ends, Control the voltage or current applied to the pair of flow channel ends based on the electrical resistance value derived by the first resistance value derivation process or the second resistance value derivation process Control method for electrophoresis apparatus.

8. A control program for causing a computer to function as an electrophoresis apparatus that separates a sample using a microchannel chip including three or more flow channel ends, one or more branch points, and a plurality of branch channels branched by the branch points and connected to each flow channel end, wherein a channel is formed in which the sample moves by electrophoresis when a voltage or current is applied to a pair of flow channel ends selected from the plurality of flow channel ends, comprising: Before separating the sample, execute a first resistance value derivation process or a second resistance value derivation process for deriving the electrical resistance value of the branch channel between the pair of flow channel ends, The first resistance value derivation process is a process of deriving the electrical resistance value based on a measurement value obtained by applying an investigation application voltage to the pair of flow channel ends, The second resistance value derivation process is a process of deriving the electrical resistance value based on a measurement value obtained by applying an investigation application current to the pair of flow channel ends, Control the voltage or current applied to the pair of flow channel ends based on the electrical resistance value derived by the first resistance value derivation process or the second resistance value derivation process Control program for electrophoresis apparatus.