Electrophoresis unit and electrophoresis method

Abstract

To prevent electric leakage to a flow path through electrodes provided at both ends of a capillary.SOLUTION: An electrophoresis unit includes: a capillary flow path through which a specimen liquid moves from upstream to downstream in a state where the capillary flow path is filled with a migration liquid; a pair of electrodes installed near both ends of the capillary flow path; a detector provided at an intermediate portion of the capillary flow path; a first flow path and a second flow path, intermediate portions of which communicate with the upstream side and the downstream side of the capillary flow path, respectively, and extend in a direction intersecting a longitudinal direction of the capillary flow path; a first supply source that supplies the specimen liquid to the first flow path; a second supply source that supplies the migration liquid to the second flow path; a pump that moves the migration liquid from the second supply source to the second flow path and moves the specimen liquid from the first supply source to the first flow path; a first auxiliary supply source that supplies an insulating fluid to the first flow path; a second auxiliary supply source that supplies an insulating fluid to the second flow path; and a switch that switches a flow path of fluid supplied to the first flow path and the second flow path from at least the first supply source and the second supply source.SELECTED DRAWING: Figure 1E

Description

[Technical field]

[0001] The present disclosure relates to a method and an apparatus for filling a capillary with a running liquid and a sample liquid when performing capillary electrophoresis. [Background technology]

[0002] Various techniques have been disclosed for methods of filling capillaries with electrophoretic liquid and specimen liquid in devices that perform capillary electrophoresis. For example, as in the technique described in Patent Document 1, a microchip structure in which reservoirs for holding liquids are provided at both ends of a separation channel and a separation buffer liquid and a sample are respectively supplied to the reservoirs at both ends is common in capillary electrophoresis. In the technique described in Patent Document 1, the amount of liquid flowing through the separation channel cannot exceed the volume of the reservoir, so it is necessary to repeat the process of supplying liquid to the reservoir and sucking it from the reservoir for sufficient washing.

[0003] In the technology described in Patent Document 2, a dispensing probe and a suction nozzle are inserted into reservoirs on both ends of a flow path, and liquid is continuously discharged and aspirated, thereby eliminating the repetitive operations as in Patent Document 1. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] JP 2005-214710 A [Patent Document 2] JP 2017-161233 A Summary of the Invention [Problem to be solved by the invention]

[0005] By providing flow paths for the sample liquid and the electrophoretic liquid upstream and downstream of the capillary, respectively, without using a reservoir structure, the amount of liquid does not depend on the volume of the reservoir. However, since electrodes are provided on both ends of the capillary, it is necessary to prevent leakage of electricity into the flow paths. [Means for solving the problem]

[0006] An electrophoresis unit according to one aspect of the present disclosure includes a capillary flow channel filled with a running solution through which analyte liquid moves from upstream to downstream, a pair of electrodes disposed near both ends of the capillary flow channel, a detector disposed midway through the capillary flow channel, a first flow channel connected to the upstream side of the capillary flow channel at its midway point and extending in a direction intersecting with the longitudinal direction of the capillary flow channel, a second flow channel connected to the downstream side of the capillary flow channel at its midway point and extending in a direction intersecting with the longitudinal direction of the capillary flow channel, and a first flow channel for supplying analyte liquid to the first flow channel. the first auxiliary supply source for supplying an insulating fluid to the first flow path that insulates the analyte liquid in contact with the electrodes within the first flow path; and a switch for switching between supplying and stopping fluid from at least the first and second supply sources to the first and second flow paths. Effect of the Invention

[0007] According to an embodiment of the present disclosure, without adopting a reservoir structure, flow paths for flowing analyte liquid and electrophoretic liquid are provided upstream and downstream of the capillary, respectively, and electrophoresis is performed with the analyte liquid in the upstream flow path and the electrophoretic liquid in the downstream flow path each sandwiched between insulating fluids, thereby preventing electric leakage into the flow paths due to electrodes provided at both ends of the capillary. [Brief description of the drawings]

[0008] [Figure 1A] FIG. 2 is a schematic diagram illustrating an overview of an electrophoretic unit according to the first embodiment. [Figure 1B] 1B is a schematic diagram illustrating a state in which an electrophoresis running solution is being introduced into a second flow path in the electrophoresis unit of FIG. 1A. FIG. [Figure 1C] 1C is a schematic diagram showing a state in which an insulating fluid is introduced into a second flow path following the state shown in FIG. 1B. FIG. [Figure 1D] FIG. 1D is a schematic diagram showing a state in which the capillary channel is filled with an electrophoretic running buffer, following the state shown in FIG. 1C. [Figure 1E] 1E is a schematic diagram showing a state in which a sample liquid and an insulating fluid are introduced into the first flow channel and electrophoresis is performed, following the state shown in FIG. 1D. FIG. [Figure 2A] FIG. 13 is a schematic diagram illustrating an overview of an electrophoretic unit according to a second embodiment. [Figure 2B] 2B is a schematic diagram illustrating a state in which an electrophoretic running solution is being introduced into a second flow path in the electrophoresis unit of FIG. 2A. FIG. [Figure 2C] FIG. 2C is a schematic diagram showing a state in which the capillary channel is filled with an electrophoretic running buffer, following the state shown in FIG. 2B. [Figure 2D] 2D is a schematic diagram showing a state in which a sample liquid is being introduced into a first flow path following the state shown in FIG. 2C. FIG. [Figure 2E] 2E is a schematic diagram showing a state in which an insulating fluid is introduced into the first flow path and the second flow path from the state shown in FIG. 2D. FIG. [Figure 2F] FIG. 2F is a schematic diagram showing a state in which the first flow path and the second flow path are opened to the outside air pressure from the state of FIG. 2E and electrophoresis is performed. [Figure 3A] FIG. 13 is a schematic diagram illustrating an overview of an electrophoretic unit according to a third embodiment. [Figure 3B] 3B is a schematic diagram illustrating a state in which an electrophoretic running solution is being introduced into a second flow path in the electrophoresis unit of FIG. 3A. FIG. [Figure 3C] 3C is a schematic diagram showing a state in which an insulating fluid is introduced into the second flow path following the state shown in FIG. 3B. FIG. [Figure 3D] 3D is a schematic diagram showing a state in which a cleaning liquid is introduced into a second flow path following the state shown in FIG. 3C. FIG. [Figure 3E] FIG. 3E is a schematic diagram showing a state in which the capillary channel is filled with an electrophoretic buffer, following the state shown in FIG. 3D. [Figure 3F]3E, and FIG. 4 is a schematic diagram showing a state in which a sample liquid, an insulating fluid, and a cleaning liquid are introduced into the first flow channel in this order. [Figure 3G] FIG. 3C is a schematic diagram showing a state in which, from the state of FIG. 3F, an insulating fluid is introduced into the first flow path and the second flow path, and the first flow path and the second flow path are opened to the outside air pressure, thereby performing electrophoresis. [Figure 4A] FIG. 13 is a schematic diagram illustrating an overview of an electrophoretic unit according to a fourth embodiment. [Figure 4B] 4B is a schematic diagram illustrating a state in which a pre-washing solution is being introduced into a second flow path in the electrophoresis unit of FIG. 4A. FIG. [Figure 4C] 4C is a schematic diagram showing a state in which an insulating fluid is introduced into the second flow path following the state shown in FIG. 4B. FIG. [Figure 4D] FIG. 4D is a schematic diagram showing a state in which the electrophoretic running buffer is being introduced into the second flow path, following the state shown in FIG. 4C. [Figure 4E] FIG. 4E is a schematic diagram showing a state in which the insulating fluid is introduced again into the second flow path following the state shown in FIG. 4D. [Figure 4F] 4F is a schematic diagram showing a state in which a cleaning liquid is introduced into a second flow path following the state shown in FIG. 4E. FIG. [Figure 4G] FIG. 4C is a schematic diagram showing a state in which the capillary channel is filled with an electrophoretic running buffer, following the state shown in FIG. 4F. [Figure 4H] This is a schematic diagram showing the state in which, from the state of Figure 4G, a pre-washing liquid, an insulating fluid, a sample liquid, an insulating fluid and a washing liquid are introduced into the first flow path in this order, and then the first flow path and the second flow path are opened to the outside air pressure and electrophoresis is performed. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0009] Hereinafter, an embodiment of the present disclosure will be described with reference to the drawings. Common reference numerals in each drawing indicate the same parts without any special explanation. In addition, each member and each part shown in each drawing is merely illustrated diagrammatically, and the size and positional relationship of the actual product are not necessarily accurately shown. In each drawing mentioned below, the right side of the capillary flow channel 11 is the upstream side, and the left side is the downstream side.

[0010] (1) First embodiment A first embodiment of the present disclosure will be described with reference to Figures 1A to 1E. Figure 1A is a schematic diagram showing an overview of an electrophoresis unit 10 of the first embodiment. Figures 1B to 1E also show schematic diagrams of an outline of a procedure in this embodiment, from filling a capillary channel 11 with a running solution RS to introducing a sample solution SS into the capillary channel upon the start of electrophoresis.

[0011] The electrophoresis unit 10 according to the embodiment of the present disclosure includes a capillary channel 11 filled with an electrophoretic running solution RS and through which a specimen liquid SS moves from upstream to downstream, a pair of electrodes 13 disposed near both ends of the capillary channel 11, a detector 12 disposed in the middle of the capillary channel 11, a first channel 20 that connects to the upstream side of the capillary channel 11 at its middle, intersects with the longitudinal direction of the capillary channel 11, and extends in an arbitrary direction, a second channel 30 that connects to the downstream side of the capillary channel 11 at its middle, intersects with the longitudinal direction of the capillary channel 11, and extends in an arbitrary direction, and a first supply source 21 that supplies a specimen liquid SS to the first channel 20. the second supply source 31 supplying the running liquid RS to the second flow path 30; a pump 40 moving the running liquid RS from the second supply source 31 to the second flow path 30 and moving the specimen liquid SS from the first supply source 21 to the first flow path 20; a first auxiliary supply source 22 supplying an insulating fluid IF to the first flow path 20 for insulating the specimen liquid SS in contact with the electrode 13 within the first flow path 20; a second auxiliary supply source 32 supplying an insulating fluid IF to the second flow path 30 for insulating the running liquid RS in contact with the electrode 13 within the second flow path 30; and a switch 50 for switching between supplying and stopping fluid from at least the first supply source 21 and the second supply source 31 to the first flow path 20 and the second flow path 30.

[0012] The capillary channel 11 is a thin tube into which a liquid is introduced by utilizing capillary action or by pressure or suction, and is made of a light-transmitting material such as glass or transparent plastic. In the electrophoresis unit 10, when the capillary channel 11 is filled with the electrophoretic liquid RS, a voltage is applied via a pair of electrodes 13 disposed near both ends of the capillary channel 11, causing the specimen liquid SS to move within the capillary channel 11 toward the opposite end. In the present disclosure, the side where the specimen liquid SS is supplied to the capillary channel 11 is referred to as the upstream side, and the side where the specimen liquid SS moves is referred to as the downstream side.

[0013] The electrophoretic solution RS is, for example, a buffer selected from various types depending on the purpose of electrophoresis. The specimen solution SS is, for example, a liquid specimen collected from a living body, such as blood, plasma, saliva, or urine, and is desirably diluted to an appropriate concentration with an appropriate buffer depending on the conditions of electrophoresis.

[0014] The detector 12 is a device that optically detects separated components of the sample liquid SS that has moved into the capillary flow channel 11 midway.

[0015] The first flow path 20 is a flow path that supplies the specimen liquid SS from the first supply source 21 to the upstream end of the capillary flow path 11 by the pump 40. The first flow path 20 intersects with the longitudinal direction of the capillary flow path 11, extends in any direction (preferably in a direction perpendicular to the longitudinal direction of the capillary flow path 11), and communicates with the upstream end of the capillary flow path 11 at its midpoint. The first supply source 21 can be filled with, for example, a reservoir or a syringe that can temporarily hold the specimen liquid SS. Excess specimen liquid SS is discharged from the end of the first flow path 20 (i.e., the opposite side to the first supply source 21). The pump 40 may be provided on either the supply side or the discharge side of the first flow path 20, or may be provided on both sides. When the pump 40 is provided on the supply side, the pump 40 moves the specimen liquid SS to the first flow path 20. When the pump 40 is provided on the discharge side, the pump 40 sucks the specimen liquid SS from the first flow path 20. In either case, the sample liquid SS moves from the first supply source 21 to the first flow path 20.

[0016] The second flow path 30 is a flow path that supplies the electrophoretic running liquid RS from the second supply source 31 to the downstream end and inside of the capillary flow path 11 by the pump 40. The second flow path 30 intersects with the longitudinal direction of the capillary flow path 11, extends in any direction (preferably in a direction perpendicular to the longitudinal direction of the capillary flow path 11), and communicates with the downstream end of the capillary flow path 11 at its midpoint. The second supply source 31 can be filled with the electrophoretic running liquid RS, for example, by a reservoir or syringe that can temporarily hold the electrophoretic running liquid RS. Excess electrophoretic running liquid RS is discharged from the end of the second flow path 30 (i.e., the opposite side to the second supply source 31). The pump 40 may be provided on either the supply side or the discharge side of the second flow path 30, or may be provided on both sides. When the pump 40 is provided on the supply side, the pump 40 moves the electrophoretic running liquid RS to the second flow path 30. When the pump 40 is provided on the discharge side, the pump 40 sucks the electrophoretic running liquid RS from the second flow path 30. In either case, the electrophoretic liquid RS moves from the second supply source 31 to the second flow path 30. In this embodiment, a pump 40 is provided on the discharge side of the first flow path 20 and the second flow path 30.

[0017] The insulating fluid IF is an insulating fluid for preventing electrical conduction to the supply side or discharge side through the sample liquid SS and the electrophoretic liquid RS in contact with the electrodes 13 in the first flow path 20 and the second flow path 30. Air is most preferable as the insulating fluid IF, but other gases (e.g., nitrogen, carbon dioxide, etc.) or liquids (e.g., vegetable oil, mineral oil, etc.) having high insulating properties may also be used. The insulating fluid IF is supplied to the first flow path 20 and the second flow path 30 from a first auxiliary supply source 22 and a second auxiliary supply source 32, respectively. The first auxiliary supply source 22 and the second auxiliary supply source 32 can be provided with an air passage or a valve that opens from the first flow path 20 and the second flow path 30, respectively, to the outside.

[0018] The switch 50 switches between supplying and stopping the fluid from at least the first supply source 21 and the second supply source 31 to the first flow path 20 and the second flow path 30. In other words, the switch 50 is a mechanism that is interposed between the first supply source 21 and the second supply source 31 and the first flow path 20 and the second flow path 30 and can switch the flow path of the fluid. The switch 50 can be, for example, a rotary valve, a mechanism combining a plurality of valves, or a mechanism for moving a nozzle. Also, as in this embodiment, the first auxiliary supply source 22 and the second auxiliary supply source 32 may introduce the insulating fluid IF into the first flow path 20 and the second flow path 30, respectively, via the switch 50. In this embodiment, the first supply source 21 and the second supply source 31, as well as the first auxiliary supply source 22 and the second auxiliary supply source 32 are provided on the supply side of the first flow path 20 and the second flow path 30 via the switch 50.

[0019] Furthermore, as in this embodiment, fluid detection sensors 80 for detecting the arrival of a fluid may be attached to the first flow path 20 and the second flow path 30. In this embodiment, in the first flow path 20, first sensors 82 are provided on the supply side and the discharge side with respect to the electrode 13. In the second flow path 30, second sensors 83 are provided on the supply side and the discharge side with respect to the electrode 13.

[0020] Hereinafter, the process from supply of the electrophoretic liquid RS and the sample liquid SS to the execution of electrophoresis in the electrophoresis unit 10 of this embodiment will be described with reference to FIGS. 1B to 1E.

[0021] First, before the electrophoretic liquid RS and the sample liquid SS are supplied, the first flow path 20 and the second flow path 30 are each filled with air as an insulating fluid IF. From this state, as shown in Fig. 1B, the switch 50 connects the second supply source 31 to the second flow path 30, and the electrophoretic liquid RS is supplied to the second flow path 30 by suction using the pump 40. Then, when the second sensor 83 on the supply side detects the leading edge of the electrophoretic liquid RS, the supply of the electrophoretic liquid RS is stopped.

[0022] Next, as shown in FIG. 1C, the switch 50 switches the supply source to connect the second auxiliary supply source 32 to the second flow path 30, and the insulating fluid IF is supplied to the second flow path 30 by suction using the pump 40. Then, as shown in FIG. 1D, when the sensor on the discharge side detects the leading edge of the electrophoretic fluid RS, the supply of the insulating fluid IF is stopped. In this state, the electrophoretic fluid RS is retained on the downstream side of the capillary flow path 11, and the electrophoretic fluid RS is sandwiched between the insulating fluids IF located on the supply side and the discharge side with respect to the position of the electrode 13. In this state, the electrophoretic fluid RS is introduced into the capillary flow path 11 from the downstream side by capillary action, pressurization, suction, or the like. When using capillary action, both ends of the capillary flow path 11 need to be opened to atmospheric pressure. On the other hand, when introducing the electrophoretic fluid RS by applying negative pressure or pressurization, a pressure difference needs to be generated in the flow paths on both ends of the capillary.

[0023] Thereafter, the switch 50 switches the supply source to connect the first supply source 21 to the first flow path 20, and the specimen liquid SS is supplied to the first flow path 20 by suction with the pump 40. Then, when the first sensor 82 on the supply side detects the front end of the specimen liquid SS, the supply of the specimen liquid SS is stopped. Next, the switch 50 switches the supply source to connect the first auxiliary supply source 22 to the first flow path 20, and the insulating fluid IF is supplied to the first flow path 20 by suction with the pump 40. Then, as shown in FIG. 1E, when the sensor on the discharge side detects the front end of the specimen liquid SS, the supply of the insulating fluid IF is stopped. In this state, the specimen liquid SS is retained on the upstream side of the capillary flow path 11, and the specimen liquid SS is sandwiched between the insulating fluid IF located on the supply side and the discharge side with respect to the position of the electrode 13. In this state, an electroosmotic flow is generated by applying a voltage to the electrodes 13 on both ends of the capillary flow channel 11, the sample liquid SS moves downstream in the capillary flow channel 11, and the components separated by electrophoresis are optically detected by the detector 12. At this time, the electrodes 13 provided in the first flow channel 20 and the second flow channel 30 are sandwiched by the insulating fluid IF on both the supply side and the discharge side, so that leakage of electricity from the electrodes 13 to the supply side and the discharge side of the electrophoresis unit 10 can be prevented.

[0024] The above-described embodiment is an electrophoresis method using a capillary flow channel 11 filled with electrophoretic liquid and through which a sample liquid SS moves from upstream to downstream, a detector 12 provided in the middle of the capillary flow channel 11, a first flow channel 20 that connects to the upstream side of the capillary flow channel 11 at its middle, intersects with the longitudinal direction of the capillary flow channel 11, and extends in an arbitrary direction, and a second flow channel 30 that connects to the downstream side of the capillary flow channel 11 at its middle, intersects with the longitudinal direction of the capillary flow channel 11, and extends in an arbitrary direction. Thus, an electrophoresis method is performed, which includes introducing the running liquid RS into the second flow path 30, introducing the running liquid RS from the second flow path 30 into the capillary flow path 11, introducing a specimen liquid SS into the first flow path 20, introducing an insulating fluid IF into the second flow path 30 across the running liquid RS in a position connecting to the capillary flow path 11, introducing an insulating fluid IF into the first flow path 20 across the specimen liquid SS in a position connecting to the capillary flow path 11, and applying a voltage between the upstream and downstream of the capillary flow path 11.

[0025] In the above electrophoresis method, it is desirable to further include introducing an insulating fluid IF into the second flow path 30 before and after introducing the electrophoretic liquid RS into the second flow path 30, and introducing an insulating fluid IF into the first flow path 20 before and after introducing the sample liquid SS into the first flow path 20.

[0026] In this embodiment, since it is not necessary to fill the entire flow path with liquid, the amount of liquid required for measuring a sample by electrophoresis can be minimized. The volume of the flow path can be designed appropriately. In this case, the electrophoresis unit 10 can be designed to introduce a known amount of fluid into the flow path and then introduce another fluid. In this case, the above-mentioned fluid detection sensor 80 is not required.

[0027] In this embodiment, the pump 40 is provided as a drainage unit on the discharge side of the first flow path 20 and the second flow path 30, but the pump 40 may be provided as a part of the configuration of the supply side switch 50. Also, the first auxiliary supply source 22 and the second auxiliary supply source 32 may be a single structure shared by the first flow path 20 and the second flow path 30.

[0028] (2) Second embodiment A second embodiment of the present disclosure will be described with reference to Figures 2A to 2F. Figure 2A is a schematic diagram showing an overview of an electrophoresis unit 10 of the second embodiment. Figures 2B to 2F also show schematic diagrams of an outline of a procedure in this embodiment, from when a running liquid RS and a sample liquid SS are introduced into a capillary channel 11 until electrophoresis is performed.

[0029] The configurations of the capillary flow path 11, the detector 12, the first flow path 20 and the second flow path 30, and the definitions of the sample liquid SS, the electrophoretic liquid RS and the insulating fluid IF are the same as those in the first embodiment.

[0030] In this embodiment, a first supply source 21 and a second supply source 31 are provided on the supply sides of the first flow path 20 and the second flow path 30 via a switch 50. Also, a pump 40 is provided on the discharge sides of the first flow path 20 and the second flow path 30, similar to the first embodiment.

[0031] In the electrophoresis unit 10 of the present embodiment, a first valve 22a for opening the first flow path 20 to atmospheric pressure is provided as the first auxiliary supply source 22, and a second valve 32a for opening the second flow path 30 to atmospheric pressure is provided as the second auxiliary supply source 32. In the present embodiment, the first valves 22a are provided on the supply side and the discharge side of the electrode 13 in the first flow path 20. Moreover, the second valves 32a are provided on the supply side and the discharge side of the electrode 13 in the second flow path 30.

[0032] Hereinafter, the process from supply of the running liquid RS and the sample liquid SS to the execution of electrophoresis in the electrophoresis unit 10 of this embodiment will be described with reference to FIGS. 2B to 2F.

[0033] 2B, the switch 50 connects the second supply source 31 to the second flow path 30 to open the flow path, and the running liquid RS is supplied to the second flow path 30 by suction using the pump 40. Then, when the second flow path 30 is filled with the running liquid RS, the switch 50 closes the flow path to stop the supply of the running liquid RS.

[0034] 2C, the electrophoretic liquid RS is introduced into the capillary flow channel 11 from the downstream side by capillary action, pressurization, suction, or the like. When using capillary action, it is necessary to open both ends of the capillary flow channel 11 to atmospheric pressure. On the other hand, when introducing the electrophoretic liquid RS by applying negative pressure or pressurization, it is necessary to generate a pressure difference between the flow channels at both ends of the capillary.

[0035] 2D, the switch 50 connects the first supply source 21 to the first flow path 20 to open the flow path, and the specimen liquid SS is supplied to the first flow path 20 by suction by the pump 40. Then, when the first flow path 20 is filled with the specimen liquid SS, the switch 50 closes the flow path to stop the supply of the specimen liquid SS.

[0036] 2E, the first valve 22a and the second valve 32a on the discharge side in the first flow path 20 and the second flow path 30 are opened, and an insulating fluid IF (for example, air) is introduced from the outside to the discharge side of the electrodes 13 of the first flow path 20 and the second flow path 30. Here, since the supply sides of the first flow path 20 and the second flow path 30 are closed spaces, the fluid in the capillary flow path 11 does not move. Then, the first valve 22a and the second valve 32a on the discharge side are closed.

[0037] 2F, in the first flow path 20 and the second flow path 30, the switch 50 is opened to communicate with the first supply source 21 and the second supply source 31, respectively, and at the same time, the first valve 22a and the second valve 32a on the supply side are opened, and an insulating fluid IF (for example, air) is introduced from the outside to the electrodes 13 of the first flow path 20 and the second flow path 30 on the supply side. After the insulating fluid IF is introduced, the switch 50 is closed to block communication with the first supply source 21 and the second supply source 31, respectively, in the first flow path 20 and the second flow path 30. In this way, by opening the first valve 22a and the second valve 32a on the supply side in the first flow path 20 and the second flow path 30, both ends of the capillary flow path 11 are opened to atmospheric pressure, and no external force due to a pressure difference with the outside air pressure acts on the fluid in the capillary flow path 11.

[0038] At this stage, the electrophoretic liquid RS is retained on the downstream side of the capillary flow channel 11, and the electrophoretic liquid RS is sandwiched between the insulating fluid IF located on the supply side and the discharge side of the electrode 13. At the same time, the specimen liquid SS is retained on the upstream side of the capillary flow channel 11, and the specimen liquid SS is sandwiched between the insulating fluid IF located on the supply side and the discharge side of the electrode 13. In this state, an electroosmotic flow is generated by applying a voltage to the electrodes 13 at both ends of the capillary flow channel 11, and the specimen liquid SS moves toward the downstream side in the capillary flow channel 11, and the components separated by electrophoresis are optically detected by the detector 12. At this time, the electrodes 13 provided in the first flow channel 20 and the second flow channel 30 are sandwiched between the insulating fluid IF on both the supply side and the discharge side, so that leakage of electricity from the electrodes 13 to the supply side and the discharge side of the electrophoresis unit 10 can be prevented.

[0039] The present embodiment described above provides an electrophoresis method using a capillary flow channel 11 in which a sample liquid SS moves from upstream to downstream, a detector 12 provided in the middle of the capillary flow channel 11, a first flow channel 20 that connects to the upstream side of the capillary flow channel 11 at its middle, intersects with the longitudinal direction of the capillary flow channel 11, and extends in an arbitrary direction, and a second flow channel 30 that connects to the downstream side of the capillary flow channel 11 at its middle, intersects with the longitudinal direction of the capillary flow channel 11, and extends in an arbitrary direction, An electrophoresis method is performed, comprising: introducing the running liquid RS into the second flow path 30; introducing the running liquid RS from the second flow path 30 into the capillary flow path 11; introducing a specimen liquid SS into the first flow path 20; introducing an insulating fluid IF into the second flow path 30 across the running liquid RS located in communication with the capillary flow path 11; introducing an insulating fluid IF into the first flow path 20 across the specimen liquid SS located in communication with the capillary flow path 11; and applying a voltage between the upstream and downstream of the capillary flow path 11.

[0040] In the above electrophoresis method, it is desirable to further include introducing an insulating fluid IF into the second flow path 30, after introducing the electrophoretic liquid RS, across a position where the second flow path 30 communicates with the capillary flow path 11, and introducing an insulating fluid IF into the first flow path 20, after introducing a sample liquid SS into the first flow path 20, across a position where the second flow path 30 communicates with the capillary flow path 11.

[0041] In this embodiment, the pump 40 is provided on the discharge side of the first flow path 20 and the second flow path 30 as a discharge unit, but the pump 40 may also be provided as part of the configuration of the switch 50 on the supply side.

[0042] (3) Third embodiment A third embodiment of the present disclosure will be described with reference to Figures 3A to 3G. Figure 3A is a schematic diagram showing an overview of an electrophoresis unit 10 of the third embodiment. Figures 3B to 3G also show schematic diagrams of an outline of a procedure in this embodiment, from when the electrophoresis liquid RS and the sample liquid SS are introduced into the capillary channel 11 until electrophoresis is performed.

[0043] The configurations of the capillary flow path 11, the detector 12, the first flow path 20 and the second flow path 30, and the definitions of the sample liquid SS, the electrophoretic liquid RS and the insulating fluid IF are the same as those in the first embodiment.

[0044] In this embodiment, a first supply source 21, a first auxiliary supply source 22, and a cleaning liquid supply source 23 are provided on the supply side of the first flow path 20 via a first switch 52 as a switch 50. Also, a second supply source 31, a second auxiliary supply source 32, and a cleaning liquid supply source 33 are provided on the supply side of the second flow path 30 via a second switch 53 as a switch 50. The meanings of the first auxiliary supply source 22 and the second auxiliary supply source 32 are the same as those in the first embodiment. The first switch 52 and the second switch 53 are both configured by a rotary valve, a mechanism combining a plurality of valves, or a mechanism for moving a nozzle.

[0045] The cleaning liquid sources 23, 33 supply cleaning liquid CL to the first flow path 20 and the second flow path 30, respectively, for cleaning the first flow path 20, the second flow path 30, and the capillary flow path 11 after the electrophoresis is completed. As the cleaning liquid CL, for example, a liquid in which a surfactant is added to an appropriate buffer or the like can be used. That is, in this embodiment, the cleaning liquid CL is introduced into the first flow path 20 via the switch 50 after the specimen liquid SS is introduced into the first flow path 20, and the cleaning liquid CL is introduced into the second flow path 30 via the switch 50 after the electrophoretic liquid RS is introduced into the second flow path 30.

[0046] In this embodiment, the first auxiliary supply source 22 further includes a first valve 22a for opening the first flow path 20 to atmospheric pressure, which is provided on the discharge side with respect to the position of the electrode 13, and the second auxiliary supply source 32 further includes a second valve 32a for opening the second flow path 30 to atmospheric pressure, which is provided on the discharge side with respect to the position of the electrode 13. Also, as in the first embodiment, a pump 40 is provided on the discharge sides of the first flow path 20 and the second flow path 30.

[0047] Hereinafter, the process from supply of the running liquid RS and the sample liquid SS to the execution of electrophoresis in the electrophoresis unit 10 of this embodiment will be described with reference to FIGS. 3B to 3G.

[0048] First, as shown in Fig. 3B, the second switch 53 connects the second supply source 31 to the second flow path 30, and the electrophoretic liquid RS is supplied to the second flow path 30 by suction using the pump 40. Next, as shown in Fig. 3C, the second switch 53 switches the supply source to connect the second auxiliary supply source 32 to the second flow path 30, and the insulating fluid IF is supplied to the second flow path 30 by suction using the pump 40.

[0049] Next, as shown in Fig. 3D, the second switch 53 switches the supply source to connect the cleaning liquid supply source 33 to the second flow path 30, and the cleaning liquid CL is supplied to the second flow path 30 by suction using the pump 40. Then, as shown in Fig. 3E, the electrophoretic liquid RS is introduced into the capillary flow path 11 from the downstream side by capillary action, pressurization, suction, or the like. When using capillary action, both ends of the capillary flow path 11 need to be opened to atmospheric pressure. On the other hand, when introducing the electrophoretic liquid RS by applying negative pressure or pressurization, a pressure difference needs to be generated in the flow paths at both ends of the capillary.

[0050] From this state, the first switch 52 connects the first supply source 21 to the first flow path 20, and the specimen liquid SS is supplied to the first flow path 20 by suction with the pump 40. Next, the first switch 52 switches the supply source to connect the first auxiliary supply source 22 to the first flow path 20, and the insulating fluid IF is supplied to the first flow path 20 by suction with the pump 40. Next, the first switch 52 switches the supply source to connect the cleaning liquid supply source 23 to the first flow path 20, and the cleaning liquid CL is supplied to the first flow path 20 by suction with the pump 40. Then, as shown in FIG. 3F, both the first switch 52 and the second switch 53 are closed, and the supply sides of the first flow path 20 and the second flow path 30 become closed spaces.

[0051] 3G, the first valve 22a and the second valve 32a on the discharge side are opened in the first flow path 20 and the second flow path 30, and insulating fluid IF is introduced from the outside to the electrodes 13 of the first flow path 20 and the second flow path 30 on the discharge side. By opening the first valve 22a and the second valve 32a on the discharge side in the first flow path 20 and the second flow path 30 in this manner, both ends of the capillary flow path 11 are opened to atmospheric pressure, and no external force due to a pressure difference with the outside air pressure acts on the fluid in the capillary flow path 11.

[0052] In this state, an electroosmotic flow is generated by applying a voltage to the electrodes 13 on both ends of the capillary flow channel 11, the sample liquid SS moves downstream in the capillary flow channel 11, and the components separated by electrophoresis are optically detected by the detector 12. At this time, the electrodes 13 provided in the first flow channel 20 and the second flow channel 30 are sandwiched by the insulating fluid IF on both the supply side and the discharge side, so that leakage of electricity from the electrodes 13 to the supply side and the discharge side of the electrophoresis unit 10 can be prevented.

[0053] After the electrophoresis is completed, the pump 40 sucks the first flow path 20 and the second flow path 30, so that the first flow path 20, the second flow path 30 and the capillary flow path 11 can be washed with the washing liquid CL.

[0054] The present embodiment described above provides an electrophoresis method using a capillary flow channel 11 in which a sample liquid SS moves from upstream to downstream, a detector 12 provided in the middle of the capillary flow channel 11, a first flow channel 20 that connects to the upstream side of the capillary flow channel 11 at its middle, intersects with the longitudinal direction of the capillary flow channel 11, and extends in an arbitrary direction, and a second flow channel 30 that connects to the downstream side of the capillary flow channel 11 at its middle, intersects with the longitudinal direction of the capillary flow channel 11, and extends in an arbitrary direction, An electrophoresis method is performed, comprising: introducing the running liquid RS into the second flow path 30; introducing the running liquid RS from the second flow path 30 into the capillary flow path 11; introducing a specimen liquid SS into the first flow path 20; introducing an insulating fluid IF into the second flow path 30 across the running liquid RS located in communication with the capillary flow path 11; introducing an insulating fluid IF into the first flow path 20 across the specimen liquid SS located in communication with the capillary flow path 11; and applying a voltage between the upstream and downstream of the capillary flow path 11.

[0055] In the above electrophoresis method, it is desirable to further include introducing an insulating fluid IF into the second flow path 30 after introducing the electrophoretic liquid RS into the second flow path 30, and further introducing an insulating fluid IF into the second flow path 30 across a position where the insulating fluid IF connects to the capillary flow path 11, and introducing an insulating fluid IF into the first flow path 20 after introducing a sample liquid SS into the first flow path 20, and further introducing an insulating fluid IF into the first flow path 20 across a position where the insulating fluid IF connects to the capillary flow path 11.

[0056] In the above electrophoresis method, it is desirable to further include introducing a cleaning liquid CL into the second flow path 30 after introducing the electrophoretic liquid RS into the second flow path 30, and introducing a cleaning liquid CL into the first flow path 20 after introducing the specimen liquid SS into the first flow path 20.

[0057] In this embodiment, the pump 40 is provided as a drainage unit on the discharge side of the first flow path 20 and the second flow path 30, but the pump 40 may be provided as part of the configuration of the switch 50 on the supply side. The first auxiliary supply source 22 and the second auxiliary supply source 32 may be a single structure shared by the first flow path 20 and the second flow path 30. Furthermore, the two cleaning liquid supply sources 23, 33 may be a single structure shared by the first flow path 20 and the second flow path 30.

[0058] (4) Fourth embodiment A fourth embodiment of the present disclosure will be described with reference to Figures 4A to 4H. Figure 4A is a schematic diagram showing an overview of an electrophoresis unit 10 of the fourth embodiment. Figures 4B to 4H also show schematic diagrams of an outline of a procedure in this embodiment, from when the electrophoresis liquid RS and the sample liquid SS are introduced into the capillary channel 11 until electrophoresis is performed.

[0059] The configurations of the capillary flow path 11, the detector 12, the first flow path 20 and the second flow path 30, and the definitions of the sample liquid SS, the electrophoretic liquid RS and the insulating fluid IF are the same as those in the first embodiment.

[0060] In this embodiment, a first supply source 21, a first auxiliary supply source 22, a cleaning liquid supply source 23, and a pre-cleaning liquid supply source 24 are provided on the supply side of the first flow path 20 via a first switch 52 as a switch 50. Also, a second supply source 31, a second auxiliary supply source 32, a cleaning liquid supply source 33, and a pre-cleaning liquid supply source 34 are provided on the supply side of the second flow path 30 via a second switch 53 as a switch 50. The meanings of the first auxiliary supply source 22 and the second auxiliary supply source 32 are the same as those in the first embodiment. The first switch 52 and the second switch 53 are both configured by a rotary valve, a mechanism combining a plurality of valves, or a mechanism for moving a nozzle.

[0061] The pre-cleaning liquid supply sources 24 and 34 supply the first flow path 20 and the second flow path 30 with a pre-cleaning liquid pCL for cleaning the first flow path 20 and the second flow path 30 before the start of electrophoresis, respectively. The cleaning liquid supply sources 23 and 33 supply the first flow path 20 and the second flow path with a cleaning liquid CL for cleaning the first flow path 20, the second flow path 30, and the capillary flow path 11 after the end of electrophoresis, respectively. As the cleaning liquid CL and the pre-cleaning liquid pCL, for example, a liquid in which a surfactant is added to an appropriate buffer or the like can be used. That is, in this embodiment, the pre-cleaning liquid pCL is introduced into the first flow path 20 via the switch 50 before the sample liquid SS is introduced into the first flow path 20, and the pre-cleaning liquid pCL is introduced into the second flow path 30 via the switch 50 before the electrophoretic liquid RS is introduced into the second flow path 30. Furthermore, in this embodiment, after the specimen liquid SS is introduced into the first flow path 20, a cleaning liquid CL is introduced into the first flow path 20 via the switch 50, and after the electrophoretic liquid RS is introduced into the second flow path 30, a cleaning liquid CL is introduced into the second flow path 30 via the switch 50.

[0062] Hereinafter, the process from supply of the electrophoretic liquid RS and the sample liquid SS to the execution of electrophoresis in the electrophoresis unit 10 of this embodiment will be described with reference to FIGS. 4B to 4H.

[0063] First, as shown in Fig. 4B, the second switch 53 connects the pre-cleaning liquid supply source 34 to the second flow path 30, and the pre-cleaning liquid pCL is supplied to the second flow path 30 by suction using the pump 40. Next, as shown in Fig. 4C, the second switch 53 switches the supply source to connect the second auxiliary supply source 32 to the second flow path 30, and the insulating fluid IF is supplied to the second flow path 30 by suction using the pump 40.

[0064] 4D, the second switch 53 switches the supply source to connect the second supply source 31 to the second flow path 30, and the running liquid RS is supplied to the second flow path 30 by suction with the pump 40. Next, as shown in FIG. 4E, the second switch 53 switches the supply source to connect the second auxiliary supply source 32 to the second flow path 30, and the insulating fluid IF is supplied to the second flow path 30 by suction with the pump 40.

[0065] Next, as shown in Fig. 4F, the second switch 53 switches the supply source to connect the cleaning liquid supply source 33 to the second flow path 30, and the cleaning liquid CL is supplied to the second flow path 30 by suction using the pump 40. Then, as shown in Fig. 4G, the electrophoretic liquid RS is introduced into the capillary flow path 11 from the downstream side by capillary action, pressurization, suction, or the like. When using capillary action, both ends of the capillary flow path 11 need to be opened to atmospheric pressure. On the other hand, when introducing the electrophoretic liquid RS by applying negative pressure or pressurization, a pressure difference needs to be generated in the flow paths at both ends of the capillary.

[0066] From this state, the first switch 52 connects the pre-cleaning liquid supply source 24 to the first flow path 20, and the pre-cleaning liquid pCL is supplied to the first flow path 20 by suction with the pump 40. Next, the first switch 52 switches the supply source to connect the first auxiliary supply source 22 to the first flow path 20, and the insulating fluid IF is supplied to the first flow path 20 by suction with the pump 40. Next, the first switch 52 switches the supply source to connect the first supply source 21 to the first flow path 20, and the specimen liquid SS is supplied to the first flow path 20 by suction with the pump 40. Next, the first switch 52 switches the supply source to connect the first auxiliary supply source 22 to the first flow path 20, and the insulating fluid IF is supplied to the first flow path 20 by suction with the pump 40. Then, the first switch 52 switches the supply source to connect the cleaning liquid supply source 23 to the first flow path 20, and the cleaning liquid CL is supplied to the first flow path 20 by suction with the pump 40.

[0067] In this state, as shown in Fig. 4H, the first flow path 20 is connected to the first auxiliary supply source 22 by the first switch 52, so that the supply side of the first flow path 20 becomes an open path 55 open to atmospheric pressure. Also as shown in Fig. 4H, the second flow path 30 is connected to the second auxiliary supply source 32 by the second switch 53, so that the supply side of the second flow path 30 also becomes an open path 55 open to atmospheric pressure. In this way, the supply sides of the first flow path 20 and the second flow path 30 become open paths 55 and are released to atmospheric pressure, so that no external force due to the pressure difference with the outside air pressure acts on the fluid in the capillary flow path 11. That is, in the electrophoresis unit 10 of this embodiment, the switch 50 can be switched to the open path 55 that opens each of the first flow path 20 and the second flow path 30 to atmospheric pressure.

[0068] 4H, a voltage is applied to the electrodes 13 at both ends of the capillary channel 11 to generate an electroosmotic flow, causing the sample liquid SS to move downstream in the capillary channel 11, and the components separated by electrophoresis are optically detected by the detector 12. At this time, the electrodes 13 provided in the first channel 20 and the second channel 30 are sandwiched by the insulating fluid IF on both the supply side and the discharge side, so that leakage of electricity from the electrodes 13 to the supply side and the discharge side of the electrophoresis unit 10 can be prevented.

[0069] After the electrophoresis is completed, the pump 40 sucks the first flow path 20 and the second flow path 30, so that the first flow path 20, the second flow path 30 and the capillary flow path 11 can be washed with the washing liquid CL.

[0070] The present embodiment described above provides an electrophoresis method using a capillary flow channel 11 in which a sample liquid SS moves from upstream to downstream, a detector 12 provided in the middle of the capillary flow channel 11, a first flow channel 20 that connects to the upstream side of the capillary flow channel 11 at its middle, intersects with the longitudinal direction of the capillary flow channel 11, and extends in an arbitrary direction, and a second flow channel 30 that connects to the downstream side of the capillary flow channel 11 at its middle, intersects with the longitudinal direction of the capillary flow channel 11, and extends in an arbitrary direction, An electrophoresis method is performed, comprising: introducing the running liquid RS into the second flow path 30; introducing the running liquid RS from the second flow path 30 into the capillary flow path 11; introducing a specimen liquid SS into the first flow path 20; introducing an insulating fluid IF into the second flow path 30 across the running liquid RS located in communication with the capillary flow path 11; introducing an insulating fluid IF into the first flow path 20 across the specimen liquid SS located in communication with the capillary flow path 11; and applying a voltage between the upstream and downstream of the capillary flow path 11.

[0071] In the above electrophoresis method, it is desirable to further include introducing an insulating fluid IF into the second flow path 30 after introducing the electrophoretic liquid RS into the second flow path 30, and further introducing an insulating fluid IF into the second flow path 30 across a position where the insulating fluid IF connects to the capillary flow path 11, and introducing an insulating fluid IF into the first flow path 20 after introducing a sample liquid SS into the first flow path 20, and further introducing an insulating fluid IF into the first flow path 20 across a position where the insulating fluid IF connects to the capillary flow path 11.

[0072] In the above electrophoresis method, it is desirable to further include introducing a cleaning liquid CL into the second flow path 30 after introducing the electrophoretic liquid RS into the second flow path 30, and introducing a cleaning liquid CL into the first flow path 20 after introducing the specimen liquid SS into the first flow path 20.

[0073] In the above electrophoresis method, it is desirable to further include introducing a pre-cleaning liquid pCL into the second flow path 30 before introducing the electrophoretic liquid RS into the second flow path 30, and introducing a pre-cleaning liquid pCL into the first flow path 20 before introducing the sample liquid SS into the first flow path 20.

[0074] In this embodiment, the pump 40 is provided as a drainage unit on the discharge side of the first flow path 20 and the second flow path 30, but the pump 40 may be provided as part of the configuration of the switch 50 on the supply side. The first auxiliary supply source 22 and the second auxiliary supply source 32 may be a single structure shared by the first flow path 20 and the second flow path 30. The two cleaning liquid supply sources 23, 33 may be a single structure shared by the first flow path 20 and the second flow path 30. Furthermore, the two pre-cleaning liquid supply sources 24, 34 may be a single structure shared by the first flow path 20 and the second flow path 30. [Industrial Applicability]

[0075] The technology of the present disclosure can be used in an electrophoresis unit and an electrophoresis method for performing capillary electrophoresis. [Explanation of symbols]

[0076] 10 electrophoresis unit 11 capillary flow path 12 detector 13 electrodes 20 first flow path 21 first supply source 22 first auxiliary supply source 22a First valve 30 Second channel 31 Second supply source 32 Second auxiliary supply source 32a Second valve 40 Pump 50 Switch 55 Open road 80 Fluid detection sensor CL cleaning fluid SS sample fluid IF insulating fluid pCL Pre-wash solution RS Running solution

Claims

1. a capillary flow path in which a sample liquid moves from upstream to downstream while being filled with an electrophoretic solution; A pair of electrodes disposed near both ends of the capillary channel; a detector provided in a middle portion of the capillary flow path; a first flow path that is connected to an upstream side of the capillary flow path at a midpoint and extends in a direction intersecting a longitudinal direction of the capillary flow path; a second flow path that is connected to a downstream side of the capillary flow path at a midpoint and extends in a direction intersecting the longitudinal direction; a first supply source that supplies the sample liquid to the first flow path; a second supply source for supplying the electrophoretic solution to the second flow path; a pump that moves the electrophoretic liquid from the second supply source to the second flow path and moves the analyte liquid from the first supply source to the first flow path; a first auxiliary supply source that supplies an insulating fluid to the first flow path, the insulating fluid insulating the sample liquid in contact with the electrodes within the first flow path; a second auxiliary supply source for supplying, to the second flow path, an insulating fluid that insulates the electrophoretic liquid in contact with the electrodes within the second flow path; a switch that switches between supply and stop of fluid from at least the first supply source and the second supply source to the first flow path and the second flow path; An electrophoresis unit having

2. The electrophoresis unit according to claim 1 , wherein the first auxiliary supply source and the second auxiliary supply source introduce insulating fluid into the first flow path and the second flow path, respectively, via the switch.

3. 3. The electrophoresis unit according to claim 2, wherein a fluid detection sensor that detects the arrival of a fluid is attached to the first flow path and the second flow path.

4. The first auxiliary supply source includes a first valve that opens the first flow path to atmospheric pressure, The second auxiliary supply source includes a second valve that opens the second flow path to atmospheric pressure. The electrophoresis unit according to claim 1 .

5. The first auxiliary supply source includes a first valve that opens the first flow path to atmospheric pressure, The second auxiliary supply source includes a second valve that opens the second flow path to atmospheric pressure. The electrophoresis unit according to claim 2 .

6. The electrophoresis unit according to claim 2 , wherein the switch is capable of switching the first flow path and the second flow path to open paths that are respectively open to atmospheric pressure.

7. After the sample liquid is introduced into the first flow path, a cleaning liquid is introduced into the first flow path via the switch; a cleaning solution is introduced into the second flow path via the switch after the electrophoretic solution is introduced into the second flow path; The electrophoretic unit according to any one of claims 1 to 6.

8. a pre-cleaning liquid is introduced into the first flow path via the switch before the sample liquid is introduced into the first flow path; a pre-washing solution is introduced into the second flow path via the switch before the electrophoresis solution is introduced into the second flow path; The electrophoresis unit according to claim 7 .

9. a capillary flow path in which a sample liquid moves from upstream to downstream while being filled with an electrophoretic solution; a detector provided in a middle portion of the capillary flow path; a first flow path that is connected to an upstream side of the capillary flow path at a midpoint and extends in a direction intersecting a longitudinal direction of the capillary flow path; a second flow path that is connected to a downstream side of the capillary flow path at a midpoint and extends in a direction intersecting the longitudinal direction; An electrophoresis method using introducing the electrophoresis solution into the second flow path; introducing the electrophoretic solution into the capillary flow channel from the second flow channel; Introducing the sample liquid into the first flow path; introducing an insulating fluid into the second flow path, sandwiching the electrophoretic liquid at a position communicating with the capillary flow path; introducing an insulating fluid into the first flow path, sandwiching the sample liquid at a position communicating with the capillary flow path; and applying a voltage between the upstream and downstream of the capillary channel; A method of electrophoresis comprising:

10. introducing an insulating fluid into the second flow path before and after introducing the electrophoretic liquid into the second flow path; and The electrophoresis method according to claim 9 , further comprising introducing an insulating fluid into the first flow path before and after introducing the sample liquid into the first flow path.

11. introducing the electrophoretic liquid into the second flow path and then introducing an insulating fluid across a position where the second flow path communicates with the capillary flow path; and introducing the sample liquid into the first flow path and then introducing an insulating fluid across a position where the sample liquid communicates with the capillary flow path; The electrophoresis method of claim 9, further comprising:

12. introducing an insulating fluid into the second flow path after introducing the electrophoretic liquid into the second flow path, and further introducing an insulating fluid into the second flow path across a position where the insulating fluid communicates with the capillary flow path; and introducing an insulating fluid into the first flow path after introducing the sample liquid into the first flow path, and further introducing an insulating fluid into the first flow path across a position where the insulating fluid communicates with the capillary flow path; The electrophoresis method of claim 9, further comprising:

13. introducing a cleaning solution into the second flow path after introducing the electrophoretic solution into the second flow path; and introducing a cleaning liquid into the first flow path after introducing the sample liquid into the first flow path; The electrophoresis method according to any one of claims 9 to 12, further comprising:

14. introducing a pre-washing solution into the second flow path before introducing the electrophoresis solution into the second flow path; and The electrophoresis method according to claim 13 , further comprising introducing a pre-wash solution into the first flow path before introducing the sample liquid into the first flow path.

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