JP2017161233A - Microchip electrophoresis device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To use a microchip repeatedly without increasing the complexity of a chip structure and without impairing cost and operability.SOLUTION: A seal-fitted member 26 is arranged on a microchip 5 that is held in a chip holding part 7, and includes open holes 64-3, 64-4 provided at positions corresponding to reservoirs 53-3, 53-4 and an elastic member 67 pressed against the microchip 5 so as to maintain airtightness between the open holes 64-3, 64-4 and the reservoirs 53-3, 53-4. When cleaning the inside of a passage 55 of the microchip 5, a dispensing probe 8 is inserted into the open hole 64-4 while maintaining airtightness between the open hole 64-4 and the dispensing probe 8. A suction nozzle 22-3 is inserted into the open hole 64-3. A cleaning liquid is discharged from the dispensing probe 8 in this state, and the cleaning liquid is flowed from the reservoir 53-4 below the pressurization port open hole 64-4 to the inside of the passage 55, and the cleaning liquid discharged from the passage 55 to the reservoir 53-3 is drawn in by the suction nozzle 22-3.SELECTED DRAWING: Figure 15

Description

  The present invention relates to a microchip electrophoresis apparatus.

  In microchip electrophoresis, a microchip for electrophoresis having a flow path including a separation flow path inside a plate-like member (hereinafter also referred to as an electrophoresis chip) is used. Samples such as DNA, RNA, or protein introduced into the separation channel of the electrophoresis chip are separated and detected by applying voltage across the separation channel and performing electrophoresis in the separation channel. The

  For example, the electrophoresis chip is formed by using a pair of plate-like members and bonding them with the flow path inside. Usually, a reservoir which is formed of a through hole and used as an access hole and a liquid reservoir is provided at a position corresponding to the flow path end. From the surface of the electrophoresis chip, the reagent and the sample are dispensed and the separation polymer (electrophoresis medium) is pressurized and filled into the reservoir. If the flow path and the reservoir are sufficiently washed after the analysis is completed, a plurality of samples can be analyzed using the same chip.

  The capacity of the reservoir is defined by the plate thickness and hole diameter of the plate member. For example, if the plate thickness is 1 mm and the hole diameter is 2 mm, the capacity of the reservoir is about 3 μL (microliter). Therefore, the reservoir cleaning process requires a dispensing and suction mechanism for 3 μL or less of the cleaning liquid, and a pressurized liquid feeding mechanism to at least one location of the reservoir.

  As a microchip electrophoresis device that performs electrophoresis automatically using an electrophoresis chip, a dispensing probe for supplying a liquid such as a separation polymer or sample to a reservoir, or a separation polymer supplied to a reservoir by pressurization Some include a pressurized liquid feeding mechanism that fills the flow path, and a suction nozzle that sucks the separated polymer overflowing from the flow path to the reservoir side (see Patent Document 1).

Japanese Patent No. 4375031

  When separating and detecting biopolymers such as nucleic acids and proteins with an electrophoresis chip, a buffer solution containing a water-soluble polymer is usually filled in the entire channel network, and at least in one of a plurality of reservoirs formed at the channel end. Dispense the sample and perform electrophoresis. After the electrophoresis is completed, (1) suction removal of the buffer solution in each reservoir, (2) dispensing of the washing solution into each reservoir, (3) suction removal of the washing solution in each reservoir, (4) at least one (5) Pressurizing and feeding the cleaning liquid, (6) Suctioning the used buffer solution discharged to other reservoirs, (7) Cleaning the inner and outer surfaces of the suction nozzle, (8) The process of washing the dispensing probe is repeated many times in this order to wash the inside of the flow channel of the electrophoresis chip and the reservoir.

  Since the discharge and suction of the cleaning liquid below the reservoir capacity are repeated, the number of loops of the cleaning process increases. In addition, the number of cleaning loops tends to increase in order to eliminate sample carryover. For this reason, there is a problem that the cleaning process takes a long time. In addition, if a cleaning liquid larger than the reservoir capacity is discharged and overflows on the chip surface, a short circuit occurs between the reservoir electrodes. Even if it does not overflow, there is a problem that the creepage distance is gradually narrowed and short-circuited when splashes are scattered on the chip surface, such as when air is pumped. In either case, it is necessary to remove the chip from the apparatus and manually clean the chip surface, which impairs the convenience of full automation.

  An object of the present invention is to repeatedly use a microchip without complicating the structure of the chip and without impairing cost and operability.

  An embodiment of a microchip electrophoresis apparatus according to the present invention includes a flow path including at least a separation flow path for separating a sample by electrophoresis, and has a reservoir opened at each end of the flow path. A chip holding part that holds the microchip so that the reservoir is on the upper surface, and a through-hole that is disposed opposite to the microchip held by the chip holding part and provided for each of the reservoirs at a position corresponding to the reservoir A member with a seal having a hole, and an elastic member pressed against the microchip so as to keep airtight between the through-hole and the reservoir; and a dispensing probe, and the movement of the dispensing probe and the dispensing probe Dispensing probe mechanism for discharging fluid from a suction nozzle and a suction nozzle, moving the suction nozzle and sucking fluid to the suction nozzle A suction nozzle mechanism for, in which a control section for controlling the operation of the dispensing probe mechanism and the suction nozzle mechanism.

  The embodiment of the microchip electrophoresis apparatus according to the present invention does not complicate the structure of the chip, and can repeatedly use the electrophoresis chip without impairing cost and operability.

It is a block diagram which shows roughly the part regarding the control part in one Embodiment of a microchip electrophoresis apparatus. It is a schematic perspective view for demonstrating the structure of the embodiment. It is a figure which shows an example of a microchip, (A) and (B) are top views which show the transparent plate-shaped member which comprises a microchip, (C) is a front view of a microchip. It is a top view which shows a specific example of the microchip. It is a schematic top view which shows the chip | tip holding | maintenance part of the state in which the electrophoresis chip is mounted. It is a schematic plan view which shows a member with a seal | sticker. It is a schematic sectional drawing which shows a part of chip | tip holding | maintenance part of the state to which the microchip and the member with a seal were attached. It is a schematic perspective view for demonstrating the operation | movement of the embodiment to process order. FIG. 6 is a schematic perspective view for explaining subsequent operations of the embodiment in order of processes. FIG. 22 is a schematic perspective view for explaining a subsequent operation of the embodiment in order of processes. FIG. 22 is a schematic perspective view for explaining a subsequent operation of the embodiment in order of processes. FIG. 22 is a schematic perspective view for explaining a subsequent operation of the embodiment in order of processes. It is a schematic sectional drawing for demonstrating the process of the washing | cleaning operation | movement in a flow path. It is a schematic sectional view for explaining a state where a dispensing probe is inserted into the pressure port # 4 and a suction nozzle is inserted into the port # 3. It is a schematic sectional drawing for demonstrating the state which is supplying the washing | cleaning liquid to the flow path of an electrophoresis chip. It is a schematic sectional drawing for demonstrating the process of the washing | cleaning operation | movement in a flow path as a reference example.

  In the embodiment of the microchip electrophoresis apparatus of the present invention, for example, a through-hole of a member with a seal disposed in an airtight manner with respect to the reservoir of the microchip can be used to increase the reservoir capacity. Therefore, the reservoir capacity can be increased without increasing the cost of consumables (microchips).

  In addition, the suction nozzle can be cleaned in the through hole by storing the cleaning liquid in the through hole arranged in an airtight manner with respect to the reservoir. In this case, a dedicated container for cleaning the suction nozzle becomes unnecessary, and the apparatus configuration can be simplified.

  Moreover, the member with a seal having an elastic member pressed against the microchip so as to keep the airtightness between the through hole and the reservoir has an effect of increasing the creepage distance between the reservoirs. Therefore, it is possible to prevent a short circuit between the reservoir electrodes without increasing the cost of the consumable item (microchip).

  Further, in the embodiment of the microchip electrophoresis apparatus of the present invention, for example, when the control unit cleans the inside of the flow path of the microchip, the control port passes through the pressure port that is the predetermined one through hole. The dispensing probe is inserted into the hole while keeping the airtightness between the pressurized port through-hole and the dispensing probe, and the cleaning solution is discharged from the dispensing probe to the reservoir under the pressurized port through-hole. You may make it control operation | movement of the said dispensing probe mechanism so that a washing | cleaning liquid may be poured in the said flow path from a certain pressurization port reservoir. As a result, cleaning can be performed by continuously flowing an excessive amount of cleaning liquid through the flow path and the reservoir, and the cleaning time can be shortened.

  In an embodiment of the microchip electrophoresis apparatus of the present invention, for example, the dispensing probe has a probe taper portion whose outer diameter becomes thinner toward the distal end side, and the probe taper portion is an inner wall of the pressure port through-hole. The airtightness between the pressurizing port through hole and the dispensing probe may be maintained by being pressed against. Thereby, airtightness between the pressure port through hole and the dispensing probe can be secured without using a member with a seal such as an O-ring.

  Further, for example, the pressure port through-hole has a through-hole taper portion whose inner diameter is smaller on the inner wall toward the tip holding portion side, and the dispensing probe is pressed against the through-hole taper portion. Airtightness between the pressurizing port through hole and the dispensing probe may be maintained. Thereby, airtightness between a pressurization port penetration hole and a dispensing probe can be secured more certainly.

  Further, in the embodiment of the microchip electrophoresis apparatus of the present invention, for example, the portion where the dispensing probe is pressed in the pressure port through-hole is a through-hole member replaceable with respect to the base material of the sealed member It may be formed by. As a result, when the part where the dispensing probe is pressed in the pressure port through hole is deteriorated due to wear or the like, the member including the part is replaced to ensure airtightness between the pressure port through hole and the dispensing probe. it can.

  Further, for example, when the inside of the flow path is cleaned, the control unit is arranged so that the liquid level of the cleaning liquid discharged from the flow path to the remaining reservoir is positioned in the remaining through-hole. The probe mechanism and the suction nozzle mechanism may be operated. Thereby, the suction nozzle can be cleaned in the reservoir.

  In addition, for example, after the controller supplies the cleaning liquid from the dispensing probe and cleans the inside of the flow path, the controller pulls out the dispensing probe from the pressurization port through hole and passes through the pressurization port through hole. Then, the suction nozzle is inserted into the pressurization port reservoir to suck and remove the cleaning liquid in the pressurization port reservoir, the suction nozzle is pulled out from the pressurization port through-hole, and the above-mentioned distribution into the pressurization port through-hole again. The probe is inserted in an airtight manner, air is discharged from the dispensing probe to flow air from the pressurized port reservoir into the flow path, and the cleaning liquid discharged from the flow path to the remaining reservoir is The dispensing probe mechanism and the suction nozzle mechanism may be operated so as to be sucked by the suction nozzle.

Hereinafter, an embodiment of a microchip electrophoresis apparatus will be described with reference to the drawings.
FIG. 1 is a block diagram schematically showing a portion related to a control unit in one embodiment of a microchip electrophoresis apparatus. FIG. 2 is a schematic perspective view for explaining the configuration of the microchip electrophoresis apparatus of this embodiment.

  The microchip electrophoresis apparatus 1 is roughly divided into a dispensing probe mechanism 6 having a dispensing probe section 2 and a metering pump 4, a tip holding section 7, a suction nozzle mechanism 19 having a suction nozzle section 16 and a suction pump section 18, A voltage application unit 24, a member 26 with a seal, a detection unit 31, and a control unit 38 are provided.

  For example, four electrophoresis chips 5 are held in the chip holding unit 7. A member 26 with a seal is disposed facing the electrophoresis chip 5. The member 26 with the seal is detachably attached to the chip holding part 7 with screws 27. The electrophoresis chip 5, the chip holding part 7, and the member 26 with a seal will be described later.

  The dispensing probe mechanism 6 dispenses separated polymers and samples, and supplies cleaning liquid and air to the reservoir of the electrophoresis chip 5. The dispensing probe unit 2 of the dispensing probe mechanism 6 includes a dispensing probe 8 and a dispensing probe moving mechanism that three-dimensionally moves the dispensing probe 8 in the horizontal direction (XY direction) and the vertical direction (Z direction). Yes. The dispensing probe 8 is made of, for example, stainless steel, and has a probe taper portion 8a whose outer diameter is narrower toward the distal end side.

  The dispensing probe mechanism 6 also includes, for example, a metering pump 4, open / close valves 9a and 9b, and a cleaning liquid container 10. The dispensing probe 8 is connected to the metering pump 4 through an open / close valve 9a. The cleaning liquid container 10 is connected to the metering pump 4 via the open / close valve 9b. The cleaning liquid container 10 contains a cleaning liquid. The cleaning liquid is pure water, for example.

  The suction nozzle mechanism 19 sucks the separated polymer, sample, or cleaning liquid in the reservoir of the electrophoresis chip 5. The suction nozzle unit 16 of the suction nozzle mechanism 19 includes suction nozzles 22-1 to 22-4 provided corresponding to the reservoirs of one electrophoresis chip 5, and nozzles that hold the suction nozzles 22-1 to 22-4. The holding unit 17 and a suction nozzle moving mechanism that moves the nozzle holding unit 17 two-dimensionally in, for example, the X direction and the Z direction are provided. The suction nozzle moving mechanism may move the suction nozzle three-dimensionally. The suction nozzles 22-1 to 22-4 are connected to pumps provided in the suction pump unit 18, respectively. The suction nozzles 22-1 to 22-4 are made of, for example, stainless steel.

  The dispensing probe moving mechanism and the suction nozzle moving mechanism are each configured by a linear motion guide mechanism such as a belt driving system or a ball screw driving system operated by rotation of a motor. However, these moving mechanisms are not limited to the linear motion guide mechanism, and are not particularly limited as long as the mechanism has a function of moving the dispensing probe and the suction nozzle to a predetermined position.

  A probe cleaning unit 14 for cleaning the dispensing probe 8 and a nozzle cleaning unit 28 for cleaning the suction nozzles 22-1 to 22-4 are provided. A cleaning liquid is supplied to the probe cleaning unit 14 and the nozzle cleaning unit 28.

  A 96-well plate 12 containing, for example, a sample, a reagent, a separation polymer, and the like is disposed within the movement range of the dispensing probe 8. The reagent and the separation polymer may be accommodated in a dedicated container and disposed near the well plate 12.

  The voltage application unit 24 applies an independent electrophoresis voltage to each of the flow path ends of the electrophoresis chip 5 for each electrophoresis chip 5.

  The detection unit 31 detects, for example, fluorescence of the sample component separated in the separation channel in the electrophoresis chip 5. For example, for each electrophoresis chip 5, the detection unit 31 includes an LED (light emitting diode) 30 that irradiates a part of the separation channel with excitation light, and a sample component that moves in the separation channel is excited by excitation light from the LED 30. And an optical fiber 32 for receiving the generated fluorescence. The detection unit 31 includes a photomultiplier tube 36 that receives the fluorescence through a filter 34 that removes the excitation light component from the fluorescence from the optical fiber 32 and transmits only the fluorescence component.

  In this embodiment, two filters 34 that transmit different fluorescence are used. Thereby, the four electrophoresis chips 5 can detect different fluorescence. However, when the same fluorescence is detected by the four electrophoresis chips 5, one filter can be used in common.

  Further, by causing the four LEDs 30 to emit light at different times, it is possible to identify and detect fluorescence from the four electrophoresis chips 5 with one photomultiplier tube 36. The excitation light source is not limited to the LED, and for example, an LD (laser diode) may be used.

  The control unit 38 controls operations of the dispensing probe mechanism 6, the suction nozzle mechanism 19, the voltage application unit 24, and the detection unit 31. The control unit 38 is realized by, for example, a microcomputer equipped with a CPU (Central Processing Unit) and a storage device. The control unit 38 is connected to a computer 40 provided outside the microchip electrophoresis apparatus 1.

  The computer 40 is realized by, for example, a personal computer (PC) or a dedicated computer. The computer 40 is an external control device for instructing the operation of the microchip electrophoretic apparatus 1 and for capturing and processing data obtained by the detection unit 31.

  3 and 4 show an example of the electrophoresis chip 5. Note that the electrophoresis chip (microchip) in the embodiment of the present invention refers to a chip having a channel formed inside and a reservoir opened at each channel end, and is not necessarily limited to a small size. It doesn't mean.

  As shown in FIG. 3, the electrophoresis chip 5 includes a pair of transparent substrates 51 and 52, for example. The transparent substrates 51 and 52 are made of, for example, quartz glass, other glass substrates, or resin substrates.

  On the surface of one substrate 52, as shown in (B), capillary grooves 54 and 55 for electrophoresis intersecting each other are formed. The other substrate 51 has through holes as reservoirs 53-1 to 53-4 at positions corresponding to the ends of the grooves 54 and 55, as shown in FIG. As shown in (C), the substrates 51 and 52 are overlapped and joined to form the electrophoresis chip 5. The capillary grooves 54 and 55 form a separation channel 55 for electrophoresis separation of the sample and a sample introduction channel 54 for introducing the sample into the separation channel 55 in the electrophoresis chip 5.

  The electrophoresis chip 5 is basically the one shown in FIG. 3, but in order to facilitate handling, an electrode terminal for applying a voltage is formed on the chip in advance as shown in FIG. Use things. FIG. 4 is a plan view of the electrophoresis chip 5.

  The four reservoirs 53-1 to 53-4 are also ports for applying a voltage to the flow paths 54 and 55. Ports # 1 and # 2 are ports located at both ends of the sample introduction channel 54. Ports # 3 and # 4 are ports located at both ends of the separation channel 55. Port # 4 constitutes a pressure port. The reservoir 53-4 constitutes a pressurized port reservoir.

  In order to apply a voltage to each port, electrode patterns 56-1 to 56-4 are formed from the inner wall surface of the reservoirs 53-1 to 53-4 constituting each port to the surface of the electrophoresis chip 5. The electrode patterns 56-1 to 56-4 are connected to the voltage application unit 24 (see FIG. 2).

  The member with a seal and the chip holding part will be described with reference to FIGS. FIG. 5 is a schematic plan view showing the chip holding portion in a state where the electrophoresis chip is mounted. FIG. 6 is a schematic plan view showing a member with a seal. FIG. 7 is a schematic cross-sectional view showing a part of the chip holding portion in a state where the electrophoresis chip and the member with the seal are attached. In FIG. 7, ports # 3 and # 4 are illustrated and ports # 1 and # 2 are not illustrated, but the configurations of ports # 1 and # 2 are the same as those of port # 3.

  As shown in FIG. 5, the chip holding unit 7 includes chip holders 71 and concave portions 74 for holding the electrophoresis chip 5 at four locations on the upper surface. Screw holes 72 for fixing the sealed member 26 are provided at two diagonal positions of the chip holding portion 7. As shown in FIG. 6, holes 62 through which the screw 27 passes are also provided at two diagonal positions of the member 26 with the seal.

  Moreover, the chip | tip holding | maintenance part 7 is provided with the escape hole 73 in which the suction nozzle 22-4 mentioned later is inserted. The escape hole 73 is provided for each holding position of the electrophoresis chip 5 at a position shifted from the holding position of the electrophoresis chip 5 in the X direction (see FIG. 2).

  The member 26 with a seal is made of, for example, resin, and includes through holes 64-1 to 64-4 at positions corresponding to the reservoirs 53-1 to 53-4. The through hole 64-4 constitutes a pressure port through hole. Moreover, the member 26 with a seal is provided with a relief hole 63 formed of a through hole into which a later-described suction nozzle 22-4 is inserted at a position corresponding to the relief hole 73 of the chip holding portion 7.

  The through holes 64-1 to 64-4 are, for example, members with a seal from the bottom of a bottomed cylindrical hole having an opening on the back surface side (chip holding unit 7 side) formed in the base material of the member 26 with a seal. A through hole provided in a through hole member 65-1 to 65-4, which is configured to be exchanged from the back side into the bottomed cylindrical hole. And a portion composed of holes.

  The through-hole members 65-1 to 65-3 are formed of, for example, a resin circular tube member having a uniform inner diameter. The inner diameters of the through-hole members 65-1 to 65-3 are dispensed so that a gap is formed between the through-hole members 65-1 to 65-3 and the dispensing probe 8 when the dispensing probe 8 is inserted. It is larger than the outer diameter of the probe 8. Further, the inner diameters of the through-hole members 65-1 to 65-3 are larger than the outer diameters of the suction nozzles 22-1 to 22-3.

  The through-hole of the through-hole member 65-4 disposed in the pressure port through-hole 64-4 includes, for example, a through-hole taper portion 65-4a whose inner diameter becomes smaller toward the tip holding portion 7 side on the inner wall thereof. The through hole tapered portion 65-4a is a portion where the tip holding portion 7 side end is smaller than the outer diameter of the dispensing probe 8, and the probe tapered portion 8a of the dispensing probe 8 is pressed. Further, the inner diameter of the through-hole member 65-4 is larger than the outer diameter of the suction nozzle 22-4.

  The sealed member 26 has an elastic member 67 that is pressed against the electrophoresis chip 5 so as to maintain airtightness between the through holes 64-1 to 64-4 and the reservoirs 53-1 to 53-4. It is provided for every 1 to 64-4. The elastic member 67 is, for example, an O-ring. The elastic member 67 is disposed on the surface of the through-hole members 65-1 to 65-4 facing the electrophoresis chip 5.

  The elastic member 67 maintains the airtightness between the through holes 64-1 to 64-4 and the reservoirs 53-1 to 53-4, so that the through holes 64-1 to 64-4 have a large capacity as necessary. Can be used as a reservoir.

  Electrode contacts 66-1 to 66-4 electrically connected to the electrode patterns 56-1 to 56-4 of the electrophoresis chip 5 are provided on the back surface side of the member 26 with the seal. The electrode contacts 66-1 to 66-4 are connected to the terminal connection portion 68 by electric wiring. The terminal connection unit 68 is connected to the voltage application unit 24 (see FIG. 2).

  The operation of the microchip electrophoresis apparatus 1 will be described with reference to FIGS. In the microchip electrophoresis apparatus 1, the electrophoresis chip 5 is repeatedly used while being fixed to the chip holding unit 7 without being moved. The operation described here is a series of operations in which the electrophoresis chip used in the previous analysis is washed, the flow path and each reservoir are filled with the separation polymer, and then the sample is dispensed and subjected to electrophoresis for analysis. It is a process. These operations are performed under the control of the control unit 38 of the microchip electrophoresis apparatus 1. 8 to 12, the illustration of the member 26 with a seal is omitted. Moreover, (A)-(T) of FIGS. 8-12 respond | corresponds to process (A)-(T) demonstrated below.

  (A) shows one electrophoresis chip 5. The electrophoresis chip 5 is equivalent to that shown in FIGS. The separation channel 55 and the sample introduction channel 54 are provided so as to intersect with each other, and reservoirs 53-1 to 53-4 are formed at the ends of the channels 54 and 55, respectively. Here, the electrophoresis chip 5 is in a state where the analysis of the previous sample is completed, and the separation polymer and the sample solution remain in the flow path and each reservoir. Further, the separated sample remains in the separation polymer in the flow channel 55.

  (B) First, in order to remove the sample solution stored in the sample storage reservoir 53-1, the nozzle holding part 17 is moved down onto the electrophoresis chip 5 and then lowered to the suction nozzle 22- 1 is inserted into the reservoir 53-1 through the through hole 64-1 (see FIG. 6).

  Here, as shown in FIG. 2, the length of the suction nozzle 22-1 is longer than that of the suction nozzles 22-2 and 22-3. The length of the suction nozzle 22-4 is longer than that of the suction nozzle 22-1. Furthermore, when the suction nozzles 22-1 to 22-3 are arranged above the reservoirs 53-1 to 53-3 (through holes 64-1 to 64-3), the suction nozzles 22-1 to 22-4 are arranged. The suction nozzle 22-4 is held by the nozzle holding portion 17 so as to be disposed above the escape holes 63 and 73 (see also FIGS. 5 and 6). Further, the suction nozzles 22-1 to 22-4 are held by the nozzle holding portion 17 so that the tip positions of the suction nozzles 22-1 to 22-4 can move toward the nozzle holding portion 17 side with respect to the nozzle holding portion 17, respectively.

  With such a configuration of the suction nozzles 22-1 to 22-4, the tip of the suction nozzle 22-1 is inserted into the reservoir 53-1 and comes into contact with the bottom of the reservoir 53-1. 3 is not inserted into the reservoirs 53-2 and 53-3, and the suction nozzle 22-4 is inserted into the escape holes 63 and 73.

  In this state, when the suction pump unit 18 (see FIG. 2) is operated, the separated polymer in the reservoir 53-1 is removed by suction through the suction nozzle 22-1. At this time, in the suction pump unit 18, for example, only the pump connected to the suction nozzle 22-1 is operated.

  In this state, the tips of the suction nozzles 22-2 and 22-3 may be positioned inside the through holes 64- and 64-3 (see FIG. 6), or the through holes 64- and 64. -3 may be disposed above.

  Further, the tip of the suction nozzle 22-4 inserted into the escape hole 73 may or may not be in contact with the bottom of the escape hole 73. However, considering the contamination of the tip of the suction nozzle 22-4, it is preferable that the tip of the suction nozzle 22-4 does not contact the bottom of the escape hole 73. The escape hole 73 may have a bottom or a through hole.

  (C) After the suction nozzles 22-1 to 22-4 are moved, the dispensing probe 8 is inserted into the reservoir 53-1 through the through hole 64-1 (see FIG. 6). At this time, a gap is formed between the dispensing probe 8 and the through hole 64-1. Then, the cleaning liquid is supplied from the dispensing probe 8 to the reservoir 53-1. The supply of the cleaning liquid from the dispensing probe 8 will be described with reference to FIG. 2. When the opening / closing valve 9 a is closed and the opening / closing valve 9 b is opened, the metering pump 4 is aspirated to bring the cleaning liquid container 10 into the metering pump 4. Then, after the cleaning liquid is sucked, the open / close valve 9b is closed, the open / close valve 9a is switched to the open state, and the metering pump 4 is discharged.

(D) After the dispensing probe 8 is moved, the suction nozzle 22-1 is again inserted into the reservoir 53-1, and the cleaning liquid is sucked and removed.
(E) The cleaning liquid is supplied again from the dispensing probe 8 to the reservoir 53-1.

  (F) The suction nozzles 22-1 to 22-3 are inserted into the reservoirs 53-1 to 53-3 through the through holes 64-1 to 64-3 (see FIG. 6). After the nozzle holding part 17 is lowered and the tip of the suction nozzle 22-1 is pressed against the bottom of the reservoir 53-1, the nozzle holding part 17 is further lowered and the suction nozzles 22-2 and 22-3 are moved. The tip contacts the bottoms of the reservoirs 53-2 and 53-3. The suction nozzle 22-4 is inserted into the escape holes 63 and 73.

  The suction pump unit 18 is operated, and the cleaning liquid in the reservoir 53-1 and the separated polymer in the reservoirs 53-2 and 53-3 are removed by suction through the suction nozzles 22-1 to 22-3. At this time, in the suction pump unit 18, for example, only pumps connected to the suction nozzles 22-1 to 22-3 are operated.

  (G) The nozzle holding part 17 is moved, and the suction nozzle 22-4 is inserted into the pressurization port reservoir 53-4 via the pressurization port through hole 64-4 (see FIG. 6). -4 contacts the bottom of the pressurized port reservoir 53-4. At this time, the suction nozzles 22-1 to 22-3 are not inserted into the reservoirs 53-1 to 53-3. The tips of the suction nozzles 22-1 to 22-3 may be disposed above the member 26 with a seal, or a relief hole may be separately provided in the member 26 with a seal and inserted into the relief hole. .

  In a state where the suction nozzle 22-4 is inserted into the pressurization port reservoir 53-4, the suction pump unit 18 is operated, and the separated polymer in the reservoir 53-4 is suctioned and removed through the suction nozzle 22-4. At this time, in the suction pump unit 18, for example, only the pump connected to the suction nozzle 22-4 is operated.

  (H) Next, the inside of the reservoirs 53-1 to 53-4 and the flow paths 54 and 55 are cleaned. This cleaning operation will be described with reference to FIGS. FIG. 13 is a schematic cross-sectional view for explaining a process of the in-channel cleaning operation. FIG. 14 is a schematic cross-sectional view for explaining a state where a dispensing probe is inserted into the pressure port # 4 and a suction nozzle is inserted into the port # 3. FIG. 15 is a schematic cross-sectional view for explaining a state where the cleaning liquid is supplied to the flow path of the electrophoresis chip.

  As shown in FIG. 13 (1), the dispensing probe 8 is inserted into the probe cleaning unit 14 (also referred to as a rinse port), the cleaning liquid is supplied from the metering pump 4, and the dispensing probe 8 is cleaned. The cleaning operation of the dispensing probe 8 may be performed in parallel with the suction operation of the separated polymer in the pressurized port reservoir 53-4 in the step (G).

  As illustrated in FIGS. 13B and 14, the suction nozzles 22-1 to 22-3 are inserted into the reservoirs 53-1 to 53-3 through the through holes 64-1 to 64-3. The suction nozzle 22-4 is inserted into the escape holes 63 and 73.

  Further, the dispensing probe 8 is inserted into the pressure port reservoir 53-4 through the pressure port through hole 64-4. At this time, as shown in FIG. 14, the probe tapered portion 8a of the dispensing probe 8 is pressed against the through hole tapered portion 65-4a of the pressure port through hole 64-4. Thereby, the airtightness between the pressurization port through-hole 64-4 and the dispensing probe 8 is maintained.

  In this state, the cleaning liquid is discharged from the dispensing probe 8, and the cleaning liquid is pressurized and fed from the pressurized port reservoir 53-4 into the channels 54 and 55. The separation polymer and the cleaning liquid discharged from the flow paths 54 and 55 to the reservoirs 53-1 to 53-3 are sucked by the suction nozzles 22-1 to 22-3. The amount of the cleaning liquid supplied from the dispensing probe 8 is a sufficient amount for cleaning the flow paths 54 and 55, for example, about 100 μL.

  Further, when the inside of the flow paths 54 and 55 is cleaned, as shown in FIG. 15, the liquid level of the cleaning liquid discharged from the flow paths 54 and 55 to the reservoirs 53-1 to 53-3 is The discharge flow rate of the cleaning liquid from the dispensing probe 8, the suction timing and the suction amount of the cleaning liquid to the suction nozzles 22-1 to 22-3 are controlled so as to be positioned in the through holes 64-1 to 64-3. . As a result, the outer wall of the tip of the suction nozzles 22-1 to 22-3 can be cleaned using the cleaning liquid overflowing from the reservoirs 53-1 to 53-3 into the through holes 64-1 to 64-3.

  After a sufficient amount of cleaning liquid for cleaning the flow paths 54 and 55 is supplied from the dispensing probe 8, the supply of the cleaning liquid from the dispensing probe 8 is stopped. The cleaning liquid remaining in the reservoirs 53-1 to 53-3 is removed by suction through the suction nozzles 22-1 to 22-3. At this time, the cleaning liquid remains in the pressurized port reservoir 53-4 and the flow paths 54 and 55.

  (I) The dispensing probe 8 is pulled out from the pressure port through hole 64-4. Moreover, the suction nozzles 22-1 to 22-3 are pulled out from the through holes 64-1 to 64-3. As shown in FIG. 13 (3), the suction nozzle 22-4 is inserted into the pressurization port reservoir 53-4 through the pressurization port through hole 64-4. The cleaning liquid remaining in the pressure port reservoir 53-4 is removed by suction through the suction nozzle 22-4.

  Before pulling out the dispensing probe 8 from the pressure port through hole 64-4, the dispensing probe 8 is raised so that the tip of the dispensing probe 8 does not come out of the pressure port through hole 64-4. In a state where a gap is formed between the probe 8 and the through hole member 65-4, the cleaning liquid is discharged from the dispensing probe 8, and the cleaning liquid is injected into the pressurized port reservoir 53-4 and the pressurized port through hole 64-4. The operation of supplying may be included. Thus, the suction nozzle 22-4 inserted into the pressurization port reservoir 53-4 can be subsequently cleaned using the cleaning liquid in the pressurization port reservoir 53-4 and the pressurization port through hole 64-4. it can.

  In addition, after the cleaning liquid is discharged from the dispensing probe 8 and the cleaning liquid is pressurized and fed from the pressurized port reservoir 53-4 into the flow paths 54 and 55, the suction nozzles 22-1 to 22-3 are supplied to the reservoirs 53-1 to 53-3. 22-3 may be inserted. In this case, the cleaning liquid overflows from the flow paths 54 and 55 and accumulates in the reservoirs 53-1 to 53-3 and the through holes 64-1 to 64-3. Thereafter, the suction nozzles 22-1 to 22-3 are inserted into the reservoirs 53-1 to 53-3 through the through holes 64-1 to 64-3, so that the outer walls of the suction nozzles 22-1 to 22-3 are inserted. Can be washed. Thereafter, the cleaning liquid is removed by suction through the suction nozzles 22-1 to 22-3. Here, the amount of the cleaning liquid supplied from the dispensing probe 8 is such that the cleaning liquid does not overflow from the through holes 64-1 to 64-3. In addition, the amount of cleaning liquid stored in the reservoirs 53-1 to 53-3 and the through holes 64-1 to 64-3 is sufficient to clean the outer walls of the suction nozzles 22-1 to 22-3. preferable.

  (J) The suction nozzle 22-4 is pulled out from the pressure port through hole 64-4. As shown in FIG. 13 (4), the suction nozzles 22-1 to 22-3 are inserted into the reservoirs 53-1 to 53-3 through the through holes 64-1 to 64-3, and the suction nozzle 22-4 is inserted. Is inserted into the relief holes 63 and 73. In addition, the dispensing probe 8 is inserted in the pressure port reservoir 53-4 through the pressure port through hole 64-4 in an airtight manner. Here, before the dispensing probe 8 is inserted into the pressurization port reservoir 53-4, the metering pump 4 is aspirated to bring the air into the dispensing probe 8.

  The suction pump unit 18 is operated so that fluid is sucked into the suction nozzles 22-1 to 22-3, and the metering pump 4 is operated to discharge air from the dispensing probe 8 to the pressurization port reservoir 53-4. And the cleaning liquid remaining in the flow paths 54 and 55 is pushed out to the reservoirs 53-1 to 53-3. The cleaning liquid pushed out to the reservoirs 53-1 to 53-3 is removed by suction through the suction nozzles 22-1 to 22-3. The amount of air supplied from the dispensing probe 8 is an amount sufficient to push the cleaning liquid remaining in the flow paths 54 and 55 to the reservoirs 53-1 to 53-3, for example, about 100 μL. As a result, the reservoirs 53-1 to 53-4 and the flow paths 54 and 55 are empty. Then, the cleaning in the reservoirs 53-1 to 53-4 and the flow paths 54 and 55 is completed.

  (K) The dispensing probe 8 is pulled out from the pressure port through hole 64-4, and the dispensing probe 8 is washed and the separated polymer is sucked into the dispensing probe 8. The suction nozzles 22-1 to 22-3 are inserted into the reservoirs 53-1 to 53-3, and the dispensing probe 8 is kept airtight in the pressure port reservoir 53-4 through the pressure port through hole 64-4. Inserted. Note that the suction nozzles 22-1 to 22-4 may be cleaned using the nozzle cleaning unit 28 after the step (J) and before the state shown in FIG.

  A predetermined amount of the separated polymer is discharged from the dispensing probe 8 to fill the separated polymer into the flow paths 54 and 55 from the pressurized port reservoir 53-4. The separated polymer discharged from the flow paths 54 and 55 to the reservoirs 53-1 to 53-3 is removed by suction through the suction nozzles 22-1 to 22-3. The amount of the separation polymer supplied from the dispensing probe 8 is a sufficient amount for filling the separation polymer into the flow paths 54 and 55, for example, about 1 μL.

  The flow path 54, 55 is filled with the separation polymer by supplying a predetermined amount of separation polymer to the pressurization port reservoir 53-4 and then pulling the dispensing probe 8 from the pressurization port through hole 64-4 once. The dispensing probe 8 is removed and the dispensing probe 8 is washed and the air is sucked into the dispensing probe 8, and the dispensing probe 8 that has sucked the air is inserted again into the pressure port through hole 64-4 while being airtight, and dispensed. A predetermined amount of air may be discharged from the probe 8 to pressurize the sealed space including the pressurized port reservoir 53-4.

  (L) The suction nozzle 22-4 is inserted into the pressure port reservoir 53-4, and the separated polymer remaining in the pressure port reservoir 53-4 is removed by suction. As a result, the separated polymer remains only in the flow paths 54 and 55.

  (M) to (P) The dispensing probe 8 sequentially dispenses a predetermined amount of separated polymer into the reservoirs 53-1 to 53-4. When the separation polymer is dispensed into the pressurized port reservoir 53-4, the separation polymer is dispensed in a state where a gap is formed between the dispensing probe 8 and the through-hole member 65-4. This is because air enters the flow path 55 when the space including the pressurized port reservoir 53-4 is sealed. Further, the order in which the separated polymer is dispensed into the reservoirs 53-1 to 53-4 is not limited to the order of the steps (M) to (P), and is not particularly limited.

  (Q) The reservoirs 53-1 to 53- are connected by the voltage application unit 24 via the electrode contacts 66-1 to 66-4 and the electrode patterns 56-1 to 56-4 (see FIGS. 2, 4 and 6). A predetermined test voltage is applied to 4 and an electrophoresis test is performed. In this migration test, for example, it is confirmed whether dust or bubbles are mixed in the flow path by detecting a current value between the electrode patterns. Here, the test voltage may be the same as the migration voltage for separating the sample, but may be a lower voltage than that.

  When it is determined in this migration test step that the separation polymer is normally filled into the flow path, the process proceeds to the next step (R) in order to inject the sample and perform analysis. When it is not determined that the separation polymer is normally filled into the flow path, the process returns to step (F) in order to refill the flow path with the separation polymer.

  For example, the number of times that the refilling of the separation polymer into the flow paths 54 and 55 is allowed is set in advance. If it is not determined that the separation polymer has been normally filled into the flow paths 54 and 55 even if the separation polymer is refilled the same number of times, the electrophoresis chip 5 is removed from the chip holder 7 and another separation polymer is filled. Replace with electrophoresis chip 5. The number of times the refilling of the separated polymer is allowed is not particularly limited, but for example, 2 or 3 times is appropriate.

  (R) The suction nozzle 22-1 is inserted into the sample storage reservoir 53-1, and the separated polymer in the reservoir 53-1 is removed by suction.

  (S) A predetermined amount of sample solution is dispensed from the dispensing probe 8 into the reservoir 53-1. The dispensing amount of the sample solution is an amount set for each electrophoresis chip 5.

  (T) The reservoirs 53-1 to 53- are connected by the voltage application unit 24 via the electrode contacts 66-1 to 66-4 and the electrode patterns 56-1 to 56-4 (see FIGS. 2, 4 and 6). A predetermined sample introduction voltage is applied to 4, and the sample is guided to the crossing position of the flow paths 54 and 55 (see FIG. 4). Thereafter, the applied voltage is switched to a predetermined voltage for electrophoretic separation, and the sample is guided into the separation channel 55 toward the reservoir 53-4 side and separated in the separation channel 55. The separated sample is detected by the detection unit 31 (see FIG. 2).

  In this embodiment, as described in the above step (H), the microchip electrophoresis apparatus 1 includes the pressure port through hole 64-4 and the airtightness between the pressure port through hole 64-4 and the dispensing probe 8. And the dispensing probe 8 is inserted, and the suction nozzles 22-1 to 22-3 are inserted into the through holes 64-1 to 64-3. The pressure port through hole 64-4 and the pressure port reservoir 53-4 are kept airtight by an elastic member 67. Thereby, the pressurization port reservoir 53-4 and the dispensing probe 8 are connected online. And the microchip electrophoresis apparatus 1 can wash | clean the electrophoresis chip 5 efficiently in a short time by supplying a washing | cleaning liquid continuously in the flow paths 54 and 55. FIG. Furthermore, since each through-hole is isolated from each other by an elastic member, the risk of short-circuiting due to splashes or liquid leakage can be avoided.

Next, as a reference example, with reference to FIG. 16, a cleaning process in the flow paths 54 and 55 when the sealed member 26 is not provided will be described.
First, the sample solution and the separation polymer in each reservoir 53-1 to 53-4 are removed by suction, and the cleaning liquid is dispensed and removed in each reservoir 53-1 to 53-4.

  Thereafter, as shown in FIG. 16, (11) cleaning of the dispensing probe 8, (12) dispensing of cleaning liquid into the pressurized port reservoir 53-4, and (13) pressurizing mechanism 100 (for example, Patent Document 1) (14) Pressurized liquid supply of the cleaning liquid using (14), (14) Suction removal of used separation polymer or cleaning liquid discharged to the reservoirs 53-1 to 53-4, (15) Cleaning liquid in the pressurized port reservoir 53-4 (16) Cleaning of the inner and outer surfaces of the suction nozzles 22-1 to 22-4 is sequentially performed.

  Here, in the step (12), the amount of the cleaning liquid injected into the reservoir 53-4 is less than the capacity of the reservoir 53-4, for example, about 3 μL so that the cleaning liquid does not overflow from the pressurized port reservoir 53-4. There is a need to. Therefore, in order to sufficiently clean the flow paths 54 and 55, it is necessary to repeat the series of processes (11) to (16) repeatedly (for example, three times or more).

  On the other hand, since the microchip electrophoresis apparatus 1 according to the embodiment of the present invention can continuously supply the cleaning liquid online in the flow paths 54, 55, the flow paths 54, 55 and the reservoirs 53-1 to 53-1. 53-4 can be efficiently cleaned in a short time.

  When the member 26 with the seal is not provided, the liquid is dispensed into the reservoir where the liquid remains, or the liquid is dispensed more than the reservoir capacity, so that the cleaning liquid or the separation polymer is converted into the chip. When the surface overflows, it is necessary to remove the electrophoresis chip 5 from the apparatus 1 and clean the surface manually, which impairs the convenience of full automation.

  In order to deal with such a problem, the microchip electrophoresis apparatus 1 includes the seal member 26 so that a liquid having a reservoir capacity or more is supplied into the reservoirs 53-1 to 53-4. In addition, the liquid overflowing from the reservoir can be accommodated in the through holes 64-1 to 64-4. This prevents the liquid from splashing from the reservoirs 53-1 to 53-4 and adhering to the upper surface of the electrophoresis chip 5.

  The capacity of the reservoirs 53-1 to 53-4 of the electrophoresis chip 5 is determined by the thickness of the plate-like member constituting the electrophoresis chip 5 and the inner diameter of the hole, and is about 2 to 3 μL, for example. For example, if the electrophoresis is continuously performed for 5 minutes or longer using this, the capacity of the reservoir is insufficient, and thus a device such as separately forming a member for increasing the reservoir capacity is required on the electrophoresis chip. Become.

  On the other hand, in the microchip electrophoresis apparatus 1 of this embodiment, the through holes 64-1 to 64-4 of the member with seal 26 constitute a space continuous with the reservoirs 53-1 to 53-4, thereby forming the through hole. Since 64-1 to 64-4 can be used as a large-capacity reservoir, it is not necessary to devise additional processing such as an electrophoresis chip.

  For example, if the thickness of the plate member is increased to increase the reservoir capacity of the electrophoresis chip, or if a separate member for increasing the reservoir capacity is provided on the chip surface around the reservoir, the manufacturing cost of the electrophoresis chip itself increases. To do. On the other hand, the microchip electrophoresis apparatus 1 does not change the design or special processing of the electrophoresis chip 5 as a consumable (without increasing the cost of the electrophoresis chip 5), and the through holes 64-1 to 64-1. The reservoir capacity can be increased by using 64-4. In addition, chip replacement can be easily performed.

  In addition, as described in the steps (H) and (I), the microchip electrophoresis apparatus 1 cleans the suction nozzles 22-1 to 22-4 in the through holes 64-1 to 64-4. be able to. Therefore, the nozzle cleaning unit 28 can be omitted from the configuration of the microchip electrophoresis apparatus 1. If the nozzle cleaning unit 28 is not provided, the configuration of the microchip electrophoresis apparatus 1 can be simplified.

  Although one embodiment of the present invention has been described above, the configuration, arrangement, numerical values, materials, and the like in the embodiment are examples, and the present invention is not limited to this, and the present invention described in the claims. Various modifications are possible within the scope of the invention.

  For example, the portion where the dispensing probe 8 is pressed in the pressure port through-hole 64-4 is formed by the through-hole member 65-4 that is replaceable with respect to the base material of the member 26 with the seal in the above embodiment. The base member of the member 26 with the seal or a member that is not supposed to be replaced may be formed.

  Moreover, although the through-holes 64-1 to 64-4 are formed using the replaceable through-hole members 65-1 to 65-4 in the above-described embodiment, the base material of the member 26 with the seal or the replacement is performed. May be formed of a member that is not assumed.

  Further, the probe taper portion 8a of the dispensing probe 8 is pressed against the through-hole taper portion 64-4a of the pressurization port through-hole 64-4, whereby the airtightness between the pressurization port through-hole 64-4 and the dispenser probe 8 is sealed. However, the method for maintaining the airtightness between the pressure port through hole 64-4 and the dispensing probe 8 is not limited to this, and any method may be used. For example, the tip of the dispensing probe may be configured to be pressed against the through hole tapered portion 64-4a, or the probe tapered portion 8a of the dispensing probe 8 may be pressed against the upper end of the inner wall of the pressure port through hole. There may be. Further, an elastic member such as an O-ring may be disposed between the dispensing probe and the pressure port through hole.

  Further, in the above embodiment, when the inside of the flow paths 54 and 55 is cleaned, the liquid level of the cleaning liquid that is intentionally discharged from the flow paths 54 and 55 to the reservoirs 53-1 to 53-3 is the through hole 64- The dispensing probe mechanism 6 and the suction nozzle mechanism 19 are operated so as to be positioned within 1 to 64-3, but the flow paths 54 and 55 are disposed while preventing the cleaning liquid from overflowing from the reservoirs 53-1 to 53-3. May be washed.

  Moreover, the electrophoresis chip used in the microchip electrophoresis apparatus according to the embodiment of the present invention is not limited to the configuration shown in FIG. 3 or FIG. 4, and the separation flow path for separating the sample by electrophoresis inside The electrophoresis chip may be any one that has a flow path including at least a reservoir and has a reservoir opened at each end of the flow path. For example, the electrophoresis chip may have a configuration in which the sample introduction channel 54 and the reservoirs 54-1 and 54-2 are not provided for the electrophoresis chip 5.

1 Microchip electrophoresis device 5 Electrophoresis chip (microchip)
6 Dispensing probe mechanism 7 Tip holding portion 8 Dispensing probe 8a Probe taper portion 19 Suction nozzle mechanism 22-1 to 22-4 Suction nozzle 26 Sealed member 38 Control unit 54 Channel 55 Separation channel 53-1 to 53- 3 Reservoir 53-4 Pressurization Port Reservoir 64-1 to 64-3 Through Hole 64-4 Pressurization Port Through Hole 64-4a Through Hole Tapered Portion 67 Elastic Member 65-4 Through Hole Member

Claims (7)

A chip that includes a flow path including at least a separation flow path for separating a sample by electrophoresis, and holds a microchip having a reservoir opened at each end of the flow path so that the reservoir is on the upper surface A holding part;
The microchip held in the chip holding part is disposed opposite to the microchip, and a through hole provided for each reservoir at a position corresponding to the reservoir, and the airtightness between the through hole and the reservoir is maintained. A sealed member having an elastic member pressed against the microchip;
A dispensing probe mechanism, comprising a dispensing probe, for moving the dispensing probe and discharging fluid from the dispensing probe;
A suction nozzle mechanism that includes a suction nozzle and moves the suction nozzle and sucks fluid to the suction nozzle;
A microchip electrophoresis apparatus comprising: a control unit that controls operations of the dispensing probe mechanism and the suction nozzle mechanism.   When the controller cleans the inside of the flow path of the microchip, the control unit has a pressure port through hole, which is the predetermined one through hole, in an airtight space between the pressure port through hole and the dispensing probe. The dispensing probe is inserted, and the washing liquid is discharged from the dispensing probe so that the washing liquid flows from the pressurized port reservoir, which is the reservoir under the pressurized port through hole, into the flow path. The microchip electrophoresis apparatus according to claim 1, wherein the operation of the dispensing probe mechanism is controlled. The dispensing probe has a probe taper portion whose outer diameter is thinner toward the tip side,
3. The microchip electrophoresis apparatus according to claim 1, wherein the probe taper portion is pressed against an inner wall of the pressure port through hole to maintain airtightness between the pressure port through hole and the dispensing probe. . The pressure port through-hole has a through-hole taper portion whose inner diameter is smaller toward the tip holding portion side on the inner wall thereof,
The microchip electricity according to any one of claims 1 to 3, wherein an airtightness between the pressurizing port through hole and the dispensing probe is maintained by pressing the dispensing probe against the through hole tapered portion. Electrophoresis device.   The part to which the said dispensing probe is pressed in the said pressurization port through-hole is formed of the through-hole member replaceable with respect to the base material of the said member with a seal | sticker. Microchip electrophoresis device.   The controller, when cleaning the inside of the flow path, the dispensing probe mechanism and the liquid level of the cleaning liquid discharged from the flow path to the remaining reservoir is positioned in the remaining through-hole The microchip electrophoresis apparatus according to claim 1, wherein the suction nozzle mechanism is operated.   The controller supplies cleaning liquid from the dispensing probe to clean the inside of the flow path, and then pulls out the dispensing probe from the pressurization port through hole and pressurizes the pressurization port through the pressurization port through hole. The suction nozzle is inserted into the port reservoir to suck and remove the cleaning liquid in the pressurization port reservoir, the suction nozzle is pulled out from the pressurization port through hole, and the dispensing probe is again airtight into the pressurization port through hole. The dispensing probe is discharged, air is discharged from the pressurized port reservoir into the flow path, and the cleaning liquid discharged from the flow path to the remaining reservoir is sucked by the suction nozzle. The microchip electrophoresis apparatus according to any one of claims 1 to 6, wherein the dispensing probe mechanism and the suction nozzle mechanism are operated as described above.

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