WO2020203510A1 - Apparatus for driving combination of microcircuit and syringe - Google Patents

Apparatus for driving combination of microcircuit and syringe Download PDF

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Publication number
WO2020203510A1
WO2020203510A1 PCT/JP2020/013180 JP2020013180W WO2020203510A1 WO 2020203510 A1 WO2020203510 A1 WO 2020203510A1 JP 2020013180 W JP2020013180 W JP 2020013180W WO 2020203510 A1 WO2020203510 A1 WO 2020203510A1
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WO
WIPO (PCT)
Prior art keywords
syringe
blood
microcircuit
piston
cells
Prior art date
Application number
PCT/JP2020/013180
Other languages
French (fr)
Japanese (ja)
Inventor
知大 久保
まどか 綾野
Original Assignee
株式会社 ＴＬ Ｇｅｎｏｍｉｃｓ
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from JP2020020665A external-priority patent/JP2020162585A/en
Application filed by 株式会社 ＴＬ Ｇｅｎｏｍｉｃｓ filed Critical 株式会社 ＴＬ Ｇｅｎｏｍｉｃｓ
Publication of WO2020203510A1 publication Critical patent/WO2020203510A1/en

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00—Other mixers; Mixing plants; Combinations of mixers
    • B01F33/45—Magnetic mixers; Mixers with magnetically driven stirrers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03B—SEPARATING SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS
    • B03B5/00—Washing granular, powdered or lumpy materials; Wet separating
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M1/00—Apparatus for enzymology or microbiology
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms

Definitions

  • the present invention relates to a driving device for a combination of a microcircuit and a syringe, and particularly to a device for classifying cells.
  • Patent Document 1 discloses a fractionator for biological components. This fractionator comprises a cartridge with a separation membrane. This fractionator drives the flow path in the cartridge with a tube pump.
  • Patent Document 2 discloses a microcircuit for hydraulically classifying cells.
  • Patent Document 3 discloses an injection device for a microreactor, which comprises a syringe, a magnetic rotating member arranged in the syringe, and a magnetic rotating power unit capable of rotating the magnetic rotating member from the outside of the syringe without contact. are doing.
  • the fine particles that can be used in the injection device for the microreactor include resin fine particles, inorganic fine particles, metal fine particles, ceramic fine particles, and the like (paragraph [0027]).
  • JP-A-2007-240304 Japanese Unexamined Patent Publication No. 2007-175684 JP-A-2007-000719
  • An object of the present invention is to provide a device that drives a combination of a microcircuit and a syringe in order to hydraulically classify cells in blood.
  • a driving device for driving a fluid device is A microcircuit for hydraulically classifying cells in blood, Blood intake and Syringe A for taking in and storing blood, A branch connecting the microcircuit, the intake, and the syringe A on three sides, A syringe B for storing the pressing liquid, which is connected to the microcircuit, and With The drive device
  • the reciprocating mechanism includes a reciprocating mechanism, a pressing mechanism, a stirring mechanism, and a control unit for controlling their coordinated operation. The reciprocating mechanism pulls the piston A of the syringe A from the intake via the branch.
  • the stirring mechanism has a magnet, and while blood is stored in the syringe A, the magnet moves a stirrer arranged in the syringe A from the outside of the syringe A, thereby causing the syringe. Stir the blood in A, Drive device.
  • the driving device further includes a mounting surface on which the reciprocating mechanism and the pressing mechanism are arranged.
  • the fluid device comprises a flat cartridge that is attached to the attachment surface when classifying cells in blood and is removed from the attachment surface after the blood has been classified.
  • the microcircuit, the intake, the syringe A, the branch, and the syringe B are arranged in the cartridge.
  • the back of the cartridge is oriented so that it faces the mounting surface of the fluid device.
  • the magnet is arranged so as to face the syringe A and move on the mounting surface.
  • the reciprocating mechanism is a connecting portion A that grips the piston rod of the piston A and an actuator A that reciprocates the connecting portion A along the longitudinal direction of the syringe A and connects to the control unit. And a hold portion for gripping the cylinder of the piston A.
  • the actuator A is arranged behind the magnet.
  • the drive device according to ⁇ 2>.
  • ⁇ 4> The magnet is a permanent magnet that reciprocates the stirrer in the syringe A along the longitudinal direction of the syringe A.
  • the stirring mechanism is an arm that holds the magnet from the side with respect to the reciprocating direction of the magnet, and an actuator M that reciprocates the arm along the longitudinal direction of the syringe A and is connected to the control unit.
  • the drive device When the fluid device is attached to the drive device, the syringe A stands with the discharge port down and the piston A up.
  • the hold portion of the reciprocating mechanism is arranged above the magnet.
  • the connecting portion A of the reciprocating mechanism is arranged above the holding portion.
  • the stirring mechanism directs the reciprocating magnet to the lower end of the cylinder of the syringe A.
  • the drive device ⁇ 4>.
  • ⁇ 6> When the control unit starts to take blood into the syringe A, the control unit starts to have the stirring mechanism stir the blood in the syringe A with the magnet.
  • the drive device according to ⁇ 1>.
  • the fluid device is A first conduit having a side having the intake and a side connecting to the branch, A second conduit located between the syringe A and the branch, A third conduit located between the branch and the microcircuit, With more
  • the drive device An intake valve that closes and opens the first conduit, A start valve that closes and opens the third conduit, With more
  • the control unit causes the intake valve to open the first conduit and the start valve to close the third conduit when the reciprocating mechanism pulls the piston A.
  • the control unit causes the intake valve to close the first conduit and the start valve to open the third conduit when the reciprocating mechanism pushes the piston A.
  • the control unit stores the program of the cooperative operation, and automatically executes the cooperative operation according to a time schedule derived from the program.
  • the drive device according to ⁇ 1> is provided. Further comprising the fluid device.
  • ⁇ 10> A method for classifying cells in blood with the separation device according to ⁇ 9>. In advance The diluent and the stirrer are placed in the syringe A. A pressing liquid is placed in the syringe B, A blood collection tube that stores blood is attached to the intake, The branch and the syringe B are connected to the upper surface of the microcircuit, and the branch is connected to the syringe B.
  • the blood flow is pushed to the opposite side.
  • the cells in the blood flow are hydraulically classified on the side not in contact with the flow of the pressing liquid, and the cells classified here are blood cells or floating cells that are not blood cells.
  • the classified cells are taken out from the outlet on the lower surface of the microcircuit.
  • a drive device for driving a combination of a fine circuit for hydraulically classifying cells in blood, a reservoir for storing pre-classified blood, and a syringe.
  • the syringe comprises at least a syringe A for taking in and storing blood and a syringe B for storing pressing fluid and connected to another inlet of the microcircuit.
  • the drive device A reciprocating mechanism, a mounting mechanism, a pressing mechanism, a stirring mechanism, and a control unit for controlling their cooperative operation are provided.
  • the reciprocating mechanism is provided in the syringe A by pulling the piston A of the syringe A.
  • the mounting mechanism mounts the discharge port of the syringe A at the inlet of the microcircuit.
  • the reciprocating mechanism continuously flows blood from the syringe A toward the microcircuit via the discharge port and the inlet.
  • the pressing mechanism the pressing liquid is continuously poured from the syringe B toward the microcircuit by pushing the piston B of the syringe B in accordance with the pushing of the piston A by the reciprocating mechanism.
  • the stirring mechanism has a magnet, and while blood is stored in the syringe A, the magnet moves a stirrer arranged in the syringe A from the outside of the syringe A, thereby causing the syringe.
  • the stirring mechanism By moving the stirrer arranged in the syringe A from the outside of the syringe A by the stirring mechanism, the blood in the syringe A and the diluent are mixed and stirred. Further, by pushing the piston A, diluted blood is continuously poured from the syringe A toward the microcircuit via the discharge port and the inlet. Further, as the reciprocating mechanism pushes the piston A, the pressing mechanism pushes the piston B of the syringe B to continuously flow the pressing liquid from the syringe B toward the microcircuit.
  • the blood flow is pushed to the opposite side. Further, the cells in the blood flow are hydraulically classified on the side not in contact with the flow of the pressing liquid, and the cells classified here are blood cells or floating cells that are not blood cells. The classified cells are taken out from the outlet on the lower surface of the microcircuit.
  • FIG. 1 Front view of the drive unit.
  • Usage diagram of drive and fluid device Usage diagram of drive and fluid device.
  • Usage diagram of drive and fluid device Usage diagram of drive and fluid device.
  • Perspective view of drive and fluid device Left side view of magnet and reciprocating mechanism.
  • Front view of the stirring mechanism and syringe A.
  • Top view of the microcircuit Partial plan view of the microcircuit. Detailed partial perspective view of the microcircuit.
  • Usage diagram of drive and fluid device Schematic diagram of the control unit. Front view of the drive unit.
  • FIG. 1 shows a drive device 70 for driving the fluid device 30.
  • the figure virtually represents a state in which the fluid device 30 is detached from the drive device 70.
  • the left side of the figure mainly represents the drive device 70.
  • the right side of the figure mainly represents the fluid device 30.
  • the fluid device 30 will be described before the drive device 70 is described.
  • the fluid device 30 includes a microcircuit 20.
  • a fine circuit is a chip having a fine fluid circuit.
  • the fine circuit may be identified by a reference numeral F (fine hydraulic circuit).
  • the microcircuit 20 hydraulically classifies the cells in the blood poured into the microcircuit 20.
  • the fluid device 30 includes a piping system 10.
  • the piping system 10 includes an intake port 50.
  • a blood collection tube 51 that stores blood, for example, whole blood, is connected to the intake port 50.
  • the fluid device 30 takes in blood from the blood collection tube 51 connected to the intake 50.
  • the fluid device 30 includes a syringe A for storing blood.
  • the syringe A and related members may be identified by reference numeral A.
  • the syringe that serves as the syringe A is the syringe 35a.
  • the syringe 35a takes blood into the syringe 35a and stores the blood in the syringe 35a.
  • the syringe 35a stores the diluted blood DB.
  • the syringe 35a includes a piston 32a that hits the piston A.
  • the syringe 35a further comprises a cylinder 34a.
  • the piston 32a reciprocates in the cylinder 34a.
  • the cylinder 34a has a discharge port 31a.
  • the cylinder 34a has a flange 36a.
  • the flange 36a is located on the opposite side of the discharge port 31a.
  • a stirrer 75 is arranged in the cylinder 34a.
  • the syringe 35a has a rod 37a.
  • the rod 37a is a piston rod of the syringe 35a.
  • One end of the rod 37a connects to the piston 32a.
  • the fluid device 30 further includes a syringe B for storing the pressing liquid.
  • a syringe B for storing the pressing liquid.
  • the syringe B and related members may be identified by reference numeral B.
  • the syringe that plays the role of syringe B is syringe 35b.
  • the syringe 35b stores the pressing liquid PL.
  • the second syringe 35b is connected to the microcircuit 20 via the fourth conduit 12.
  • the syringe 35b includes a piston 32b that hits the piston B.
  • the syringe 35b further comprises a cylinder 34b.
  • the piston 32b reciprocates in the cylinder 34b.
  • the cylinder 34b has a discharge port 31b.
  • the cylinder 34b has a flange 36b.
  • the flange 36b is located on the opposite side of the discharge port 31b.
  • the syringe 35b has a rod 37b.
  • the rod 37b is a piston rod of the syringe 35b. One end of the rod 37b connects to the piston 32b.
  • the piping system 10 includes a first conduit 11a, a second conduit 11b, a third conduit 11c, a fourth conduit 12, and a branch 15.
  • the branch 15 communicates between the microcircuit 20, the intake 50 and the syringe 35a on three sides.
  • the first conduit 11a has an end on the side having the intake 50 and an end on the side connecting to the branch 15.
  • the second conduit 11b is located between the syringe 35a and the branch 15.
  • the third conduit 11c is located between the branch 15 and the microcircuit 20.
  • the second conduit 11b is located between the syringe 35a and the branch 15. One end of the second conduit 11b is connected to the discharge port 31a. The other end of the second conduit 11b connects to the branch 15.
  • the third conduit 11c is located between the branch 15 and the microcircuit 20.
  • One end of the third conduit 11c connects to the branch 15.
  • the other end of the third conduit 11c connects to the microcircuit 20.
  • the fourth conduit 12 is located between the syringe 35b and the microcircuit 20. One end of the fourth conduit 12 is connected to the discharge port 31b. The other end of the fourth conduit 12 connects to the microcircuit 20.
  • the blood collection tube 51 has a cap 52.
  • the cap 52 may be a rubber stopper.
  • the ventilation needle 53 may be attached to the blood collection tube 51.
  • the ventilation needle 53 penetrates the cap 52.
  • the air outside the blood collection tube 51 is guided to the lumen of the blood collection tube 51.
  • the blood collection tube 51 is housed in the blood collection tube holder 54.
  • the intake 50 may be connected to the blood collection tube 51 via the blood collection tube holder 54.
  • the drive device 70 and the fluid device 30 can be combined to form an integrated separation device.
  • a separator with a drive device 70 separates the target cell from other cells or components in the blood.
  • the drive device 70 includes a reciprocating mechanism 71a, a pressing mechanism 71b, and a stirring mechanism 71c.
  • the drive device 70 further includes a control unit 80 that controls these coordinated operations.
  • the reciprocating mechanism 71a includes a grip portion 72a that corresponds to the connecting portion A.
  • the reciprocating mechanism 71a further includes an actuator 73a that corresponds to the actuator A. Since the reciprocating mechanism 71a is related to the syringe A, the reciprocating mechanism may be identified by the reference numeral A below.
  • the pressing mechanism 71b includes a grip portion 72b.
  • the pressing mechanism 71b further includes an actuator 73b. Since the pressing mechanism 71b is related to the syringe B, the pressing mechanism may be identified by the reference numeral B below.
  • the stirring mechanism 71c includes an arm 72c, an actuator 73c corresponding to the actuator M, and a magnet 74.
  • the stirring mechanism 71c may be identified by a reference numeral M (mixing).
  • the arm 72c holds the magnet 74.
  • the actuator 73c moves the magnet 74 via the arm 72c.
  • the mode in which the stirring mechanism 71c moves the magnet 74 is not limited to this.
  • the magnet 74 may be a permanent magnet or an electromagnet.
  • the stirring mechanism 71c stirs the diluted blood DB in the cylinder 34a with the stirrer 75.
  • the stirrer 75 has a ferromagnet.
  • the magnetic force of the magnet 74 affects the stirrer 75.
  • the magnet 74 moves the stirrer 75 while blood is stored in the cylinder 34a as the diluted blood DB.
  • the stirring mechanism 71c can continuously stir the diluted blood DB to suppress the precipitation of blood cells or floating cells that are not blood cells in the diluted blood DB.
  • control unit 80 is connected to the actuator 73a, the actuator 73b, and the actuator 73c.
  • the control unit 80 causes the stirring mechanism 71c to cooperate with the reciprocating mechanism 71a and the pressing mechanism 71b via these actuators.
  • the drive device 70 includes an intake valve 76a and a start valve 76b.
  • the control unit 80 connects to these valves. Under the control of the control unit 80, the intake valve 76a can close and open the first conduit 11a. Under control by the control unit 80, the start valve 76b can close and open the third conduit 11c.
  • FIG. 2 to 4 show how the fluid device 30 is operated by using the drive device 70. First, how the drive device 70 and the fluid device 30 are combined will be described with reference to FIG.
  • FIG. 2 shows how the blood BL is taken into the syringe 35a.
  • the grip portion 72a grips the flange 38a.
  • the mode of connection between the reciprocating mechanism 71a and the syringe 35a is not limited to this.
  • the grip portion 72a is connected to the actuator 73a. By transmitting the force of the actuator 73a to the flange 38a, the grip portion 72a can move the piston 32a up and down in the drawing via the rod 37a.
  • the grip portion 72b grips the flange 38b.
  • the mode of connection between the pressing mechanism 71b and the syringe 35b is not limited to this.
  • the grip portion 72b is connected to the actuator 73b. By transmitting the force of the actuator 73b to the flange 38b, the grip portion 72b can move the piston 32b downward via the rod 37b. The grip portion 72b may further move the piston 32b upward.
  • the microcircuit 20 includes an inlet 21a and an inlet 21b.
  • the microcircuit 20 further includes an outlet 22a, an outlet 22b, and an outlet 22c. Details of the structure and function of the microcircuit 20 will be described later.
  • control unit 80 causes the reciprocating mechanism 71a to pull the piston 32a via the rod 37a and the flange 38a. At this time, the control unit 80 causes the intake valve 76a to open the first conduit 11a. The control unit 80 further closes the third conduit 11c to the start valve 76b at this time.
  • the reciprocating mechanism 71a takes in blood BL from the intake port 50 via the branch 15 into the cylinder 34a of the syringe 35a.
  • a blood collection tube 51 is attached to the intake port 50.
  • the blood collection tube 51 stores the collected blood BL in advance.
  • the blood collection tube 51 may be a vacuum blood collection tube.
  • Blood BL may be undiluted whole blood.
  • a reagent may be added to the blood collection tube 51 in advance and mixed with undiluted whole blood in advance.
  • the cylinder 34a stores the diluent DL in advance.
  • the diluent DL dilutes the blood BL in the cylinder 34a.
  • a stirrer 75 is arranged in advance in the cylinder 34a. Under the control of the control unit 80, the magnet 74 of the stirring mechanism (M) may move the stirrer 75. The magnet 74 may mix the diluent DL and the blood BL.
  • FIG. 3 shows how the blood BL has been taken into the syringe 35a.
  • the control unit 80 causes the reciprocating mechanism 71a to stop the operation of pulling the piston 32a.
  • the stirring mechanism (M) moves the stirrer 75 via the magnet 74. This movement may be continued from FIG.
  • the stir bar 75 mixes the liquid in the cylinder 34a well. Diluted blood DB is obtained in the cylinder 34a by mixing the diluted solution and blood BL. Stirring also suppresses the sedimentation of blood cells in the diluted blood DB.
  • FIG. 4 shows how the diluted blood DB is poured into the fine circuit 20.
  • the control unit 80 causes the reciprocating mechanism 71a to push the piston 32a via the rod 37a and the flange 38a. At this time, the control unit 80 closes the first conduit 11a to the intake valve 76a. At this time, the control unit 80 further opens the third conduit 11c to the start valve 76b.
  • the control unit 80 further causes the pressing mechanism 71b to push the piston 32b.
  • the pressing mechanism 71b does this as the reciprocating mechanism 71a pushes the piston 32a.
  • the cylinder 34b of the syringe 35b stores the pressing liquid PL in advance. The function of the pressing liquid PL in the fine circuit 20 will be described later.
  • the reciprocating mechanism 71a continuously flows the diluted blood DB from the syringe 35a toward the microcircuit 20 via the branch 15.
  • the pressing mechanism 71b continuously flows the pressing liquid PL from the cylinder 34b toward the fine circuit 20.
  • the diluted blood DB flows from the cylinder 34a, and the pressing liquid PL flows from the cylinder 34b into the microcircuit 20 in parallel with each other.
  • the stirring mechanism (M) moves the stirrer 75 via the magnet 74. This movement may be continued from FIG.
  • the stirrer 75 stirs the diluted blood DB well. Stirring suppresses the sedimentation of blood cells in the diluted blood DB. As a result, the number of blood cells per unit volume in the diluted blood DB is made uniform.
  • the syringe 35a can send the diluted blood DB thus homogenized to the microcircuit 20. While the diluted blood DB is sent to the microcircuit 20, fluctuation of the number of blood cells per unit volume is suppressed depending on the time zone.
  • piston 32a and the piston 32b operate cooperatively under the control of the control unit 80. These feed the diluted blood DB and the pressing liquid PL into the microcircuit 20. Under the control of the control unit 80, the piston 32a, the stirrer 75, and the piston 32b operate in cooperation with each other.
  • the piston 32a, the intake valve 76a, and the start valve 76b operate cooperatively under the control of the control unit.
  • the blood BL in the blood collection tube 51 is sent to the microcircuit 20. It is preferable that the two valves cooperate further in addition to the above three elements.
  • At least one of the intake valve 76a and the start valve 76b may be replaced with a check valve. Further, these valves may be replaced with a three-way stopcock installed at the branch 15.
  • FIG. 5 shows a fluid device 30 in the form of a cartridge and a drive device 70 made in accordance with the fluid device 30.
  • the drive device 70 further includes a mounting surface 86.
  • a reciprocating mechanism 71a and a pressing mechanism 71b are arranged on the mounting surface 86.
  • the drive device 70 may further include guides 87a and 87b.
  • the guides 87a and 87b may be arranged on the mounting surface 86.
  • the fluid device 30 is composed of a flat plate cartridge.
  • the fluid device 30 is attached to the mounting surface 86 when classifying cells in blood.
  • a cover may further cover the mounting surface 86 and the fluid device 30. After finishing the classification of blood, the fluid device 30 is removed from the mounting surface 86.
  • the microcircuit 20, the intake port 50, the syringe 35a corresponding to the syringe A, the branch 15 and the syringe 35b corresponding to the syringe B are arranged in a plane in the cartridge constituting the fluid device 30. ing. The positions of these members are fixed by the case 55.
  • the fluid device 30 is attached to the drive device 70. At this time, the back surface of the cartridge-shaped fluid device 30 faces the mounting surface 86.
  • the guides 87a and 87b receive the bottom of the cartridge-like fluid device 30.
  • FIG. 5 also shows the positional relationship between each syringe and the drive device 70 after mounting.
  • the hold portion 79a grips the cylinder 34a.
  • the grip portion 72a grips the flange 38a.
  • the hold portion 79b grips the cylinder 34b.
  • the grip portion 72b grips the flange 38b.
  • the guides 87a and 87b define the mounting height of the cartridge-shaped fluid device 30, thereby aligning the heights of the members.
  • the hold portion 79a includes a support 78a.
  • the support 78a supports the lower surface of the flange 36a so that the cylinder 34a does not fall.
  • the support 78a preferably supports the lower surface of the flange 36a on both the left and right sides of the cylinder 34a. Further, the support 78a restrains the cylinder 34a so as not to move in the left-right direction in the drawing.
  • the hold portion 79a further includes a holding tool 77a.
  • the presser 77a presses the upper surface of the flange 36a to restrain the cylinder 34a so that the cylinder 34a does not protrude from the support 78a.
  • the presser 77a presses the cylinder 34a.
  • the flange 36a is sandwiched between the lower surface of the holding tool 77a and the upper surface of the support 78a.
  • the presser 77a preferably presses the upper surface of the flange 36a on both the left and right sides of the piston 32a inserted into the cylinder 34a. It is preferable that the lower surface of the holding tool 77a and the upper surface of the support 78a sandwich the flange 36a on both the left and right sides of the cylinder 34a.
  • the hold portion 79b includes a support 78b.
  • the support 78b supports the lower surface of the flange 36b so that the cylinder 34b does not fall.
  • the support 78b preferably supports the lower surface of the flange 36b on both the left and right sides of the cylinder 34b. Further, the support 78b restrains the cylinder 34b so as not to move in the left-right direction in the drawing.
  • the hold portion 79b further includes a holding tool 77b.
  • the holding tool 77b may be capable of restraining the cylinder 34b so that the cylinder 34b does not protrude from the support 78b by pressing the upper surface of the flange 36b.
  • the pressing tool 77b may be able to press the cylinder 34b.
  • the flange 36b is sandwiched between the lower surface of the holding tool 77b and the upper surface of the support 78b.
  • the presser 77b may press the upper surface of the flange 36b on both the left and right sides of the piston 32b inserted into the cylinder 34b.
  • the lower surface of the presser foot 77b and the upper surface of the support 78b may sandwich the flange 36b.
  • the magnet 74 faces the cylinder 34a.
  • the magnet 74 is arranged so as to move on the mounting surface 86.
  • the magnet 74 reciprocates in the operating area OA.
  • the operating area OA may be formed by a through hole or a recess provided on the mounting surface 86. In the figure, the operating area OA is a through hole.
  • the magnet 74 can be brought closer to the cylinder 34a by bringing the back surface of the flat plate-shaped fluid device 30 closer to the mounting surface 86. Therefore, the magnetic force of the magnet 74 is efficiently transmitted to the stirrer 75 in the cylinder 34a.
  • the case 55 has an access window 59.
  • the intake valve 76a reaches the first conduit 11a through the access window 89.
  • the intake valve 76a catches the first conduit 11a.
  • the intake valve 76a closes the inside of the first conduit 11a by crushing the first conduit 11a.
  • the intake valve 76a opens the inside of the first conduit 11a by stopping crushing the first conduit 11a.
  • the start valve 76b reaches the third conduit 11c through the access window 59.
  • the start valve 76b catches the third conduit 11c.
  • the start valve 76b closes the inside of the third conduit 11c by crushing the third conduit 11c.
  • the start valve 76b opens the inside of the third conduit 11c by stopping crushing the third conduit 11c.
  • the fluid device 30 in the form of a cartridge further includes a collection container 56 and a drainage container 57.
  • the collection vessel 56 receives cells of interest classified by the microcircuit 20, such as nucleated blood cells.
  • the drainage container 57 receives cell-free fractions and unintended cells generated by the classification operation.
  • the collection container 56 and the drainage container 57 are arranged in the case 55.
  • the collection container 56 can be taken out from the case 55.
  • the drainage container 57 may be enclosed in the case 55.
  • each component of the drive device 70 is separated from the fluid device 30.
  • the fluid circuit required for classification is mounted on the fluid device 30.
  • the drive device 70 does not include the components of the fluid device 30.
  • the drive device 70 provides the fluid device 30 with the power required for classification.
  • the fluid device 30 can be attached to the drive device 70 as a cartridge each time classification is required. Further, the fluid device 30 after classification can be removed from the drive device 70 and discarded.
  • the fluid device 30 may be disposablely replaced for each classification operation.
  • the drive device 70 may be used repeatedly. This allows cells in the blood to be classified using a clean fluid device 30 for each blood sample.
  • the stir bar 75 may also be disposable and replaced with the fluid device 30.
  • the drive device 70 is independent of each syringe and the microcircuit 20. Therefore, the blood sample is unlikely to adhere to the drive device 70. This prevents the drive device 70 from mediating contamination between different blood samples.
  • FIG. 6 shows the magnet 74 and the reciprocating mechanism 71a observed in the VI cross section shown in FIG. In this figure, it is assumed that the cartridge-shaped fluid device is already attached to the drive device. The cartridge case is omitted in the figure.
  • the actuator 73a is arranged behind the magnet 74.
  • the rear side means that the actuator 73a is located on the side opposite to the cylinder 34a with the magnet 74 in between.
  • the actuator 73a reciprocates the grip portion 72a along the longitudinal direction of the syringe 35a.
  • the actuator 73a moves the rod 37a from the back side of the magnet 74.
  • the operating area OA is located behind the cylinder 34a and faces the cylinder 34a.
  • the actuator 73a may be located behind the operating area OA.
  • the operating area OA may face the actuator 73a.
  • the grip portion 72a may straddle the operating area OA.
  • FIG. 7 shows a state in which the stirring mechanism 71c and the syringe 35a are selected and observed from the front.
  • the fluid device is already mounted on the drive unit.
  • the cartridge case is omitted in the figure.
  • the actuator 73c reciprocates the arm 72c along the longitudinal direction of the syringe 35a.
  • the arm 72c holds the magnet 74 from the side with respect to the reciprocating direction of the magnet 74.
  • the arm 72c inserts the magnet 74 from the side of the syringe 35a.
  • the magnet 74 reciprocates the stirrer 75 in the syringe 35a along the longitudinal direction of the syringe 35a.
  • the magnet 74 may be a permanent magnet or an electromagnet.
  • the magnet 74 is a permanent magnet.
  • the syringe 35a stands with the discharge port 31a at the bottom and the piston 32a at the top.
  • the syringe 35a may be upright.
  • the hold portion 79a is located above the magnet 74 and the stirrer 75.
  • the grip portion 72a is located above the hold portion 79a.
  • the magnet 74 may drop the stirrer 75 in the cylinder 34a during the reciprocating motion of the magnet 74.
  • An example is when the stirrer 75 collides with the piston 32a.
  • the stirring mechanism 71c directs the magnet 74 to the lower end of the cylinder 34a.
  • the reciprocating motion of the magnet 74 is preferably one that folds back at the lower end of the cylinder 34a. As a result, the magnet 74 can pick up the stirrer 75 that the magnet 74 has dropped again. Therefore, blood agitation continues.
  • the drive device 70 drives the fluid device 30.
  • the role of the fluid device 30 is to perform hydraulic classification by sending the diluted blood DB and the pressing liquid PL to the microcircuit 20.
  • the hydraulic description of the microcircuit 20 will be described below.
  • the microcircuit 20 is a flow path chip for separating floating cells such as blood cells.
  • the configuration of the microcircuit 20 is not limited to the following embodiment.
  • FIG. 8 shows a microcircuit 20 in a plan view.
  • the microcircuit 20 has a main flow path 23.
  • One end of the main flow path 23 is an inlet 21a.
  • the other end of the main flow path 23 is an outlet 22c.
  • the microcircuit 20 further has a subchannel 24.
  • the end of the auxiliary flow path 24 is the inlet 21b.
  • the end of the sub-flow path 24 is connected to the main flow path 23 at the merging portion 28.
  • the main flow path 23 has flow path parts 25a to 25d in order from the inlet 21a to the outlet 22c.
  • the flow path parts 25a to d are connected from the inlet 21a to the outlet 22c.
  • the inlet 21a shown in FIG. 8 is connected to the syringe 35a containing the diluted blood DB. From the syringe 35a, the diluted blood DB is sent to the inlet 21a at a predetermined flow rate. The diluted blood DB enters the flow path part 25a via the inlet 21a.
  • the diluted blood DB shown in FIG. 8 is preferably diluted before being introduced into the microcircuit 20.
  • the dilution rate can be 2 to 500 times. In this example, the dilution rate may be 50 times. Dilution is done with phosphate buffered saline.
  • the flow rate of the diluted blood DB per unit time can be 1 to 1000 ⁇ l / min. For example, it may be any of 5,10,15,20,25,30,35,40,45,50,55,60,65,70,75,80,85,90,95 and 100 ⁇ l / min.
  • the processing time may be 1 minute to 300 minutes.
  • the fine circuit 20 may be any of 5, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 210, 240 and 270 minutes.
  • the liquid obtained by diluting, for example, 15 ml of whole blood in one classification may be processed by the fine circuit 20.
  • the microcircuit 20 shown in FIG. 8 has a subchannel 24.
  • the subchannel 24 is connected to the syringe 35b.
  • the pressing liquid PL is stored in the syringe 35b.
  • Pressing liquid PL is a liquid that does not contain floating cells.
  • Pressing liquid PL is a liquid that does not easily damage blood cells and other cells.
  • the pressing liquid PL may contain a buffer liquid.
  • the buffer may be PBS.
  • Both the branch flow paths 26a and 26b shown in FIG. 8 are flow paths that branch from the main flow path 23.
  • the branch flow path 26a and the branch flow path 26b branch from the main flow path 23 in this order from the upstream side.
  • the branch flow paths 26a and 26b are arranged on the side facing the sub flow path 24 with the main flow path 23 in between.
  • Each of the branch flow paths 26a and 26b shown in FIG. 8 has a plurality of small flow paths branching from the main flow path 23.
  • the small flow paths are lined up from the upstream to the downstream of the main flow path 23.
  • the branch flow paths 26a and 26b reach the outlets 22a and 22b, respectively.
  • the fine flow paths in the branch flow paths 26a and 26b merge before the outlets 22a and 22b, respectively.
  • the flow path part 25d reaches the outlet 22c.
  • FIG. 9 shows a microcircuit 20 in which the vicinity of the flow path part 25c is magnified.
  • the figure schematically shows the process of separating floating cells by the microcircuit 20.
  • the branch flow path 26a is represented by 10 small channels
  • the branch flow path 26b is represented by 3 small channels.
  • FIGS. 9 and 10 are taken from Patent Document 2 and partially modified so as to be suitable for the description of this embodiment. The classification mechanism is described in particular detail in Patent Document 2.
  • the diluted blood DB continuously flows from the upstream of the flow path part 25b.
  • Diluted blood DB contains a large amount of cells.
  • the flow of the pressing liquid PL is continuously contacted with the flow of the diluted blood DB from the side thereof.
  • the pressing liquid PL continuously pushes the flow of the diluted blood DB to the opposite side of the pressing liquid PL while flowing in the same direction as the diluted blood DB.
  • the pressing liquid PL continuously pushes the cells flowing through the main flow path 23 from the side of the main flow path 23.
  • the floating cells are continuously pushed toward the branch flow path 26a and the branch flow path 26b, and in the flow path part 25c, the floating cells continuously flow into these branch flow paths.
  • annuclear erythrocytes 27 continuously flow into the branch flow path 26a.
  • the anucleated erythrocytes 27 in the diluted blood DB are hydraulically classified in the channel part 25c. The classification is continuously performed on the side of the flow of the diluted blood DB that is not in contact with the flow of the pressing liquid PL.
  • the branch flow path 26a acts as a removal flow path for the anucleated erythrocytes 27.
  • the inscribed diameter of the fine flow path of the branch flow path 26a is 11 to 19 ⁇ m.
  • the inscribed diameter may be any of 12, 13, 14, 15, 16, 17, and 18 ⁇ m.
  • nucleated cells 29a-c continuously flow into the branch flow path 26b.
  • the nucleated cells 29a-c in the diluted blood DB are hydraulically classified. The classification is continuously performed on the side of the flow of the diluted blood DB that is not in contact with the flow of the pressing liquid PL.
  • Cell suspension CS is continuously obtained from the branch flow path 26b.
  • the branch flow path 26b functions as a recovery flow path for the nucleated cells 29a-c.
  • the inscribed diameter of the fine channel of the branch flow path 26b is smaller than the inscribed diameter of the fine channel of the branch flow path 26a.
  • the inscribed diameter of the fine flow path of the branch flow path 26b is 17 to 30 ⁇ m.
  • the inscribed diameter may be any of 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28 and 29 ⁇ m.
  • the diameter of nucleated cells including nucleated red blood cells is considered to be 11 to 13 ⁇ m.
  • the inscribed diameter of each of the branch flow paths 26a and 26b shown in FIG. 9 is the diameter of the inscribed circle in the orthogonal cross section of the fine flow path.
  • the cross section of each microchannel is square.
  • the cross section of the microchannel may be another polygon or a circle. The same is true for other branch channels.
  • Floating cells and plasma not taken up in the branch flow paths 26a and 26b shown in FIG. 9 continuously pass through the flow path part 25d as a flow-through FT. After that, it reaches the exit 22c shown in FIG.
  • aggregated blood cells are included in the flow-through FT.
  • FIG. 10 shows the details of the microcircuit while focusing on the flow path part 25c.
  • the value of the inscribed diameter of the microchannel is not equal to the maximum value of the diameter of the suspended cells to be classified. Therefore, the hydraulic classification according to this embodiment is different from simple filtration. The hydraulic classification according to this embodiment will be described below.
  • FIG. 10 shows the flow path part 25c. Further, a branch flow path 26a is represented. For the sake of simplicity, only one fine flow path constitutes the branch flow path 26a. In the description of FIG. 10, the fine flow path constituting the branch flow path 26a is simply referred to as a branch flow path 26a.
  • the liquid flow LF is continuously introduced into the flow path part 25c.
  • the liquid flow LF contains the above-mentioned diluted blood DB and the pressing liquid PL. These liquids are partially mixed in the liquid flow LF.
  • Nucleated cells 29a as large cells and annuclear erythrocytes 27 as small cells are suspended in the fluid flow LF. In the figure, the nucleated cell 29a is drawn on behalf of other nucleated cells.
  • the portion of the liquid flow LF introduced into the branch flow path 26a is referred to as the liquid flow LE.
  • the portion of the liquid flow LF that is not introduced into the branch flow path 26a and flows downstream is referred to as the liquid flow LG.
  • the flow rate of the liquid flow LE is smaller than a certain value.
  • the flow rate is proportional to the cross section of the liquid flow LE.
  • the liquid flow LE is located on the inner wall of the flow path part 25c on the branch flow path 26a side.
  • the flow rate of the liquid flow LE is also proportional to the flow rate of the liquid flow LE in the branch flow path 26a.
  • annuclear erythrocytes 27 flowing in the liquid flow LE are introduced into the branch flow path 26a.
  • more than half of the volume of the nucleated cell 29a belongs to the liquid flow LG side. Nucleated cells 29a make only partial contact with the fluid LE. Therefore, the nucleated cells 29a are not introduced into the branch flow path 26a. At this time, the diameter of the nucleated cell 29a may be smaller than the inscribed diameter of the branch flow path 26a. If the flow rate of the liquid flow LE becomes large, the cross section of the liquid flow LE becomes large. In this case, it is conceivable that the nucleated cells 29a are swallowed by the liquid flow LE and are guided to the branch flow path 26a.
  • the nucleated cells 29a are carried further downstream on the liquid flow LG. As described above, a fluid having a certain size or larger and containing no suspended cells can be recovered from the branch flow path 26a. Nucleated cells 29a and other nucleated cells are also classified downstream.
  • FIG. 11 shows a flow chart of the operation of the microcircuit (F) for the work of classifying cells in blood. Further, a flow chart of the operation of the reciprocating mechanism (A), the pressing mechanism (B) and the stirring mechanism (M) for operating the fine circuit (F) is shown.
  • FIG. 12 shows the state of the drive device 70 and the fluid device 30 prior to blood uptake.
  • blood BL is collected in the blood collection tube 51 as shown in FIG. 12 as a preliminary preparation.
  • the blood BL is whole blood.
  • the blood collection tube 51 storing the blood BL is attached to the inlet 50. Further, by injecting the diluted solution DL into the syringe 35a in advance, this is placed in the syringe 35a. Further, a stirrer 75 is also arranged in the syringe 35a. Further, by injecting the pressing liquid PL into the syringe 35b in advance, this is placed in the syringe 35b. As soon as the preparations are completed, the classification work will start.
  • step S91 of FIG. 11 the inside of the microcircuit (F) and the surrounding conduit is immersed in a liquid.
  • the syringe 35a supplies the diluent DL into the second conduit 11b, the branch 15, the third conduit 11c, and the microcircuit 20.
  • the intake valve 76a is closed and the start valve 76b is opened.
  • step S91 shown in FIG. 11 the stirring mechanism (M) is stopped.
  • step S92 of FIG. 11 the immersion of the fine circuit (F) is stopped.
  • the liquid feeding to the fine circuit (F) is stopped.
  • the fine circuit (F) also pauses.
  • the stirring mechanism (M) may also be paused in step S92.
  • step S93 of FIG. 11 the reciprocating mechanism (A) pulls the piston.
  • the intake valve 76a is opened and the start valve 76b is closed.
  • the valve By operating the valve, a route from the blood collection tube 51 to the syringe 35a via the intake 50 and the branch 15 is formed.
  • the piston 32a By pulling the piston 32a, the blood BL is taken into the syringe 35a along this route. That is, as the volume of the syringe 35a is expanded, a predetermined amount of blood BL is taken into the syringe 35a from the intake port 50 via the branch 15.
  • the stirring mechanism (M) moves the stirrer 75 from the outside of the syringe 35a to stir the diluent DL and the blood so that the suspended cells in the blood do not settle in the syringe 35a. Further, the mixing of the blood BL before dilution and the diluted solution DL may be sufficient by stirring with the stirrer 75.
  • step S93 shown in FIG. 11 the microcircuit (F) and the pressing mechanism (B) are stopped.
  • step S94 shown in FIG. 11 the drawing of blood by the reciprocating mechanism (A) is stopped.
  • the fine circuit 20 corresponding to the fine circuit (F) and the pressing mechanism 71b corresponding to the pressing mechanism (B) are stationary.
  • the pressing mechanism 71b may continue pressing without pausing.
  • the stirring mechanism (M) continues stirring the diluted blood DB.
  • step S95 shown in FIG. 11 blood cells in blood are classified by a microcircuit (F).
  • the start valve 76b is opened and released as shown in FIG. Further, the intake valve 76a is closed and all the pressure is directed to the fine circuit 20. As a result, a route from the syringe 35a to the microcircuit 20 via the branch 15 is formed.
  • step S95 shown in FIG. 11 the reciprocating mechanism (A) and the pressing mechanism (B) press against each syringe.
  • the reciprocating mechanism 71a pushes the piston 32a. Pushing the piston 32a may be simultaneous with the formation of a route by each valve.
  • the syringe 35a continuously flows the diluted blood DB into the microcircuit 20 by the pressure generated by the piston 32a.
  • the pressing mechanism 71b further pushes the piston 32b.
  • the syringe 35b continuously flows the pressing liquid PL into the microcircuit 20 by the pressure generated by the piston 32b.
  • the microcircuit 20 continuously classifies suspended cells in the diluted blood DB while using the pressing solution PL.
  • blood cells or floating cells that are not blood cells are hydraulically classified in the microcircuit 20. Details of the hydraulic classification have been described with reference to FIGS. 8-10.
  • the microcircuit 20 can separate and concentrate PBMC (peripheral blood mononuclear cells). Further, the classified cells may be taken out from the discharge port on the lower surface of the microcircuit 20.
  • PBMC peripheral blood mononuclear cells
  • step S95 After processing a predetermined amount of diluted blood DB in step S95 shown in FIG. 11, the pressing by the reciprocating mechanism (A) and the pressing mechanism (B) is stopped in step S96. Classification in the fine circuit (F) is also suspended. Further, the stirring of the diluted blood by the stirring mechanism (M) may be stopped in accordance with these. As described above, all the processes are completed, and the classification work is completed in step S99. The classification work may be resumed if necessary.
  • FIG. 13 schematically shows the control unit 80.
  • the control unit 80 includes a sequencer 81.
  • the sequencer 81 is a PLC (programmable logic controller).
  • the sequencer 81 includes a non-volatile memory 82.
  • the memory 82 stores the program of the cooperative operation of each mechanism shown in FIG.
  • the sequencer 81 automatically executes the cooperative operation according to the time schedule derived from the program stored in the memory 82.
  • the control unit 80 further includes motor drivers 83a, 83b and 83c.
  • the motor drivers 83a, 83b and 83c are connected to the sequencer 81, respectively.
  • the motor drivers 83a, 83b and 83c are connected to the actuators 73a, 73b and 73c, respectively.
  • the actuators 73a, 73b and 73c are components of the reciprocating mechanism (A), the pressing mechanism (B) and the stirring mechanism (M), respectively.
  • the motor drivers 83a, 83b and 83c operate the reciprocating mechanism (A), the pressing mechanism (B) and the stirring mechanism (M), respectively.
  • control unit 80 is further connected to the intake valve 76a and the start valve 76b. Both the intake valve 76a and the start valve 76b may be a pinch valve operated by a solenoid.
  • the control unit 80 operates the intake valve 76a and the start valve 76b in accordance with the operation of the reciprocating mechanism (A).
  • the drive device 70 further includes a power supply 85.
  • the power supply 85 is connected to the sequencer 81 and the motor drivers 83a, 83b and 83c, respectively.
  • the power supply 85 supplies to the control unit 80.
  • the control unit 80 operates with the electric power of the power source 85.
  • the power supply 85 supplies electric power to the actuators 73a, 73b and 73c via the motor drivers 83a, 83b and 83c, respectively.
  • Each motor driver and actuator is powered by power 85.
  • the power supply 85 may be connected to the intake valve 76a and the start valve 76b.
  • the power supply 85 may supply the power required to operate the intake valve 76a and the start valve 76b. All the functions of the control unit 80 may be completed in the drive device 70. Some functions may be outside the drive 70.
  • FIG. 14 is a front view showing a modified example of the drive device.
  • the drive device 40 makes the microcircuit 20, the reservoir 45, the syringe 35a, and the syringe 35b cooperate with each other.
  • the reservoir 45 stores preclassified blood. These elements are not integrated as the fluid device 30 shown in FIG. 1 or the like or as a cartridge thereof.
  • the drive device 40 shown in FIG. 14 does not use the three-way branch 15 shown in FIG. 1 or the like or the blood intake 50 connected to the branch 15. Further, in order to arrange the traveling direction of blood in the branch 15 shown in FIG. 1 and the like, opening and closing of the valve 76a and the valve 76b is not controlled. The drive device 40 is otherwise common to the drive device 70 shown in FIG. 1 and the like.
  • the drive device 40 includes a control unit 48.
  • the control unit 48 includes a reciprocating mechanism 71a, a mounting mechanism 46, a pressing mechanism 71b, and a stirring mechanism 71c.
  • the drive device 40 includes a control unit 48 that controls these cooperative operations.
  • the control unit 48 differs from the control unit 80 in that it does not control the valves 76a and 76b shown in FIG. 1 and the like, but instead controls the mounting mechanism 46 shown in FIG.
  • the control unit 48 is otherwise common to the control unit 80.
  • the reciprocating mechanism 71a takes in blood from the reservoir 45 toward the inside of the syringe 35a by pulling the piston 32a of the syringe 35a.
  • the syringe 35a takes in blood through the discharge port 31a.
  • the mounting mechanism 46 transports the syringe 35a from the location of the reservoir 45 to the location of the microcircuit 20.
  • the mounting mechanism 46 mounts the discharge port 31a of the syringe 35a at the inlet 21a of the microcircuit 20.
  • an adapter 43a is attached to the inlet 21a of the microcircuit 20.
  • the mounting mechanism 46 inserts the discharge port 31a into the adapter 43a.
  • the inlet 21a of the microcircuit 20 and the discharge port 31a of the syringe 35a are coupled via an adapter 43a.
  • the adapter 43a may be freely attached to and detached from the inlet 21a of the discharge port 31a. After mounting the discharge port 31a, the adapter 43a may not be able to remove the discharge port 31a from the inlet 21a.
  • the discharge port 31b of the syringe 35b is connected to the inlet 21b on the upper surface of the microcircuit 20.
  • An adapter 43b is attached to the inlet 21b of the microcircuit 20.
  • the inlet 21a of the microcircuit 20 and the discharge port 31a of the syringe 35a are coupled via an adapter 43a.
  • the stirrer arranged in the syringe 35a is moved by the stirring mechanism 71c from the outside of the syringe 35a to mix and stir the blood in the syringe 35a and the diluent to obtain the diluted blood DB. While the diluted blood DB is stored in the syringe 35a, the magnet 74 moves the stirrer 75 from the outside of the syringe 35a to stir the blood in the syringe 35a.
  • the reciprocating mechanism 71a continuously flows the diluted blood DB from the syringe 35a toward the microcircuit 20 via the discharge port 31a and the inlet 21a by pushing the piston 32a.
  • the pressing mechanism 71b continuously flows the pressing liquid PL from the syringe 35b toward the microcircuit 20 by pushing the piston B of the syringe 35b in accordance with the reciprocating mechanism 71a pushing the piston 32a.
  • the cells in the blood stored in the reservoir 45 shown in FIG. 14 can be classified by the microcircuit 20. Details of classification in the fine circuit 20 are performed as shown in FIGS. 8 to 10.

Abstract

A fluid device (30) comprises a microcircuit (20), an intake opening (50) for blood, a syringe A (35a) that accumulates the blood, and a syringe B (35b) for accumulating a pressing liquid. A drive apparatus (70) comprises a reciprocating mechanism (71a), a pressing mechanism (71b), a stirring mechanism (71c), and a control unit (80). The reciprocating mechanism (71a) pulls a piston A (32a) to thereby take blood into the syringe A (35a). The reciprocating mechanism (71a) furthermore pushes the piston A (32a) to thereby cause blood to flow continuously into the microcircuit (20). The pressing mechanism (71b) pushes a piston B (32b) to thereby cause a pressing liquid PL to flow continuously into the microcircuit (20). A magnet (74) of the stirring mechanism (71c) causes a stirring element (75) to move from outside the syringe A (35a).

Description

微細回路とシリンジとの組み合わせに対する駆動装置Drive device for the combination of microcircuits and syringes
　本発明は微細回路とシリンジとの組み合わせに対する駆動装置に関し、特に細胞を分級するための装置に関する。 The present invention relates to a driving device for a combination of a microcircuit and a syringe, and particularly to a device for classifying cells.
　特許文献１は生体成分の分画装置を開示している。この分画装置は分離膜を備えたカートリッジを備える。この分画装置はカートリッジ内の流路をチューブポンプで駆動する。特許文献２は細胞を水力学的に分級するための微細回路を開示している。 Patent Document 1 discloses a fractionator for biological components. This fractionator comprises a cartridge with a separation membrane. This fractionator drives the flow path in the cartridge with a tube pump. Patent Document 2 discloses a microcircuit for hydraulically classifying cells.
　特許文献３はシリンジ、該シリンジ内に配置された磁性回転部材及び、該磁性回転部材をシリンジ外部から非接触で回転可能な磁性回転動力部を有することを特徴とするマイクロリアクター用注入装置を開示している。当該マイクロリアクター用注入装置で使用することができる微粒子は、樹脂微粒子、無機微粒子、金属微粒子、セラミック微粒子等が例示される（段落[0027]）。 Patent Document 3 discloses an injection device for a microreactor, which comprises a syringe, a magnetic rotating member arranged in the syringe, and a magnetic rotating power unit capable of rotating the magnetic rotating member from the outside of the syringe without contact. are doing. Examples of the fine particles that can be used in the injection device for the microreactor include resin fine particles, inorganic fine particles, metal fine particles, ceramic fine particles, and the like (paragraph [0027]).
特開２００７－２４０３０４号公報JP-A-2007-240304 特開２００７－１７５６８４号公報Japanese Unexamined Patent Publication No. 2007-175684 特開２００７－０００７１９号公報JP-A-2007-000719
　本発明は血液中の細胞を水力学的に分級するために微細回路とシリンジとの組み合わせを駆動する装置を提供することを目的とする。 An object of the present invention is to provide a device that drives a combination of a microcircuit and a syringe in order to hydraulically classify cells in blood.
＜１＞　流体デバイスを駆動するための駆動装置であって、
　前記流体デバイスは、
　　血液中の細胞を水力学的に分級するための微細回路と、
　　血液の取入口と、
　　血液を取り込むとともに蓄えるためのシリンジＡと、
　　前記微細回路、前記取入口及び前記シリンジＡからなる三方の間を連絡する分岐と、
　　押圧液を蓄えるためのシリンジＢであって前記微細回路に接続するものと、
　を備え、
　前記駆動装置は、
　往復機構と、押圧機構と、撹拌機構と、これらの協調動作を制御する制御ユニットと、を備え
　前記往復機構は、前記シリンジＡの有するピストンＡを引くことで、前記取入口から前記分岐を経由して前記シリンジＡ内に血液を取り込み、さらに前記ピストンＡを押すことで前記シリンジＡから前記分岐を経由して前記微細回路に向かって血液を連続的に流し入れ、
　前記押圧機構は、前記往復機構が前記ピストンＡを押すのに合わせて、前記シリンジＢの有するピストンＢを押すことで前記シリンジＢから前記微細回路に向かって前記押圧液を連続的に流し入れ、
　前記撹拌機構は磁石を有し、ここで前記シリンジＡ内に血液が蓄えられている間に、前記磁石が前記シリンジＡ内に配置された撹拌子を前記シリンジＡの外側から動かすことで前記シリンジＡ内の血液を撹拌する、
　駆動装置。
＜２＞　前記駆動装置は前記往復機構と、前記押圧機構とが配置された取り付け面をさらに備え、
　前記流体デバイスは血液中の細胞を分級する時に前記取り付け面に装着され、さらに血液の分級を終えた後に前記取り付け面から取り外される、平板状のカートリッジからなり、
　前記カートリッジ中に、前記微細回路と、前記取入口と、前記シリンジＡと、前記分岐と、前記シリンジＢとが配置されており、
　装着の際、前記カートリッジの背面が前記流体デバイスの前記取り付け面に対向するように向けられ、
　前記磁石は前記シリンジＡに対向するとともに、前記取り付け面上を移動するように配置されている、
　＜１＞に記載の駆動装置。
＜３＞　前記往復機構は前記ピストンＡのピストンロッドを把持する連結部Ａと、前記連結部Ａを前記シリンジＡの長手方向に沿って往復運動させるアクチュエーターＡであって前記制御ユニットと接続するものと、前記ピストンＡのシリンダーを把持するホールド部とを有し、
　前記磁石の後ろ側に前記アクチュエーターＡが配置されている、
　＜２＞に記載の駆動装置。
＜４＞　前記磁石は前記シリンジＡの長手方向に沿って前記撹拌子を前記シリンジＡ内で往復運動させる永久磁石であり、
　前記撹拌機構は前記磁石の往復運動方向に対する側方から前記磁石を保持するアームと、前記アームを前記シリンジＡの長手方向に沿って往復運動させるアクチュエーターＭであって前記制御ユニットに接続するものとをさらに備える、
　＜３＞に記載の駆動装置。
＜５＞　前記流体デバイスが前記駆動装置に対して装着されているときに前記シリンジＡは吐出口を下に、前記ピストンＡを上にして立っており、
　前記磁石の上方に前記往復機構の前記ホールド部が配置されており、
　前記ホールド部の上方に前記往復機構の前記連結部Ａが配置されており、
　前記撹拌機構は前記シリンジＡの前記シリンダーの下端まで前記往復運動する前記磁石を向かわせる、
　＜４＞に記載の駆動装置。
＜６＞　前記制御ユニットは、血液を前記シリンジＡ内に取り込み始めた時に、前記撹拌機構に前記磁石で前記シリンジＡ内の血液を撹拌させ始める、
　＜１＞に記載の駆動装置。
＜７＞　前記流体デバイスは、
　　前記取入口を有する側と前記分岐に接続する側とを有する第１導管と、
　　前記シリンジＡと前記分岐との間に位置する第２導管と、
　　前記分岐と前記微細回路との間に位置する第３導管と、
　をさらに備え、
　前記駆動装置は、
　　前記第１導管を閉鎖及び開放する取入バルブと、
　　前記第３導管を閉鎖及び開放する開始バルブと、
　をさらに備え、
　前記制御ユニットは、前記往復機構が前記ピストンＡを引く時に、前記取入バルブに前記第１導管を開放させるとともに、前記開始バルブに前記第３導管を閉鎖させ、
　前記制御ユニットは、前記往復機構が前記ピストンＡを押す時に、前記取入バルブに前記第１導管を閉鎖させるとともに、前記開始バルブに前記第３導管を開放させる、
　＜１＞に記載の駆動装置。
＜８＞　前記制御ユニットは前記協調動作のプログラムを記憶しており、前記プログラムから導き出されるタイムスケジュールに沿って、前記協調動作を自動実行する、
　＜１＞に記載の駆動装置。
＜９＞　＜１＞に記載の前記駆動装置を備え、
　さらに前記流体デバイスを備える、
　血液内の細胞の分離装置。
＜１０＞　＜９＞に記載の分離装置で、血液内の細胞を分級する方法であって、
　予め、
　　前記シリンジＡ内に希釈液と前記撹拌子とを配置し、
　　前記シリンジＢ内に押圧液を配置し、
　　前記取入口に血液を蓄えた採血管を取り付け、
　　前記微細回路の上面に前記分岐と前記シリンジＢとを接続し、
　前記往復機構で、前記シリンジＡの有するピストンＡを引くことで、前記取入口から前記分岐を経由して前記シリンジＡ内に血液を取り込み、
　前記撹拌機構で前記シリンジＡ内に配置された撹拌子を前記シリンジＡの外側から動かすことで前記シリンジＡ内の血液と希釈液とを混合撹拌し、
　さらに前記ピストンＡを押すことで前記シリンジＡから前記分岐を経由して前記微細回路に向かって希釈された血液を連続的に流し入れ、
　さらに前記往復機構が前記ピストンＡを押すのに合わせて、前記押圧機構で前記シリンジＢの有するピストンＢを押すことで前記シリンジＢから前記微細回路に向かって前記押圧液を連続的に流し入れ、
　前記微細回路内で前記シリンジＡが作る血液の流れに対して、その側方より前記シリンジＢが作る押圧液の流れを接触させることで前記血液の流れを反対側に押し込み、
　さらに前記押圧液の流れとは接触していない側にて前記血液の流れの中の細胞を水力学的に分級し、ここで分級される細胞は血球又は血球ではない浮遊細胞である、
　前記微細回路の下面の排出口から分級された細胞を取り出す、
　方法。
＜１１＞　前記駆動装置は繰り返し使用する一方で、前記流体デバイスを使い捨て交換することで、
　血液のサンプルごとにクリーンな流体デバイスを用いて血液内の細胞を分級する、
　＜１０＞に記載の方法。
＜１２＞　血液中の細胞を水力学的に分級するための微細回路と分級前の血液を蓄えるためのリザーバーとシリンジとの組み合わせを駆動するための駆動装置であって、
　前記シリンジは少なくとも、血液を取り込むとともに蓄えるためのシリンジＡと、押圧液を蓄えるためのシリンジであって前記微細回路の他の入口に接続するシリンジＢと、を含み、
　前記駆動装置は、
　往復機構と、装着機構と、押圧機構と、撹拌機構と、これらの協調動作を制御する制御ユニットと、を備え
　前記往復機構は、前記シリンジＡの有するピストンＡを引くことで、前記シリンジＡ内に向かって、前記リザーバーから血液を取り込み、
　前記装着機構は、前記シリンジＡの吐出口を前記微細回路の入口に装着し、
　前記往復機構は、前記ピストンＡを押すことで前記シリンジＡから前記吐出口及び前記入口を経由して前記微細回路に向かって血液を連続的に流し入れ、
　前記押圧機構は、前記往復機構が前記ピストンＡを押すのに合わせて、前記シリンジＢの有するピストンＢを押すことで前記シリンジＢから前記微細回路に向かって前記押圧液を連続的に流し入れ、
　前記撹拌機構は磁石を有し、ここで前記シリンジＡ内に血液が蓄えられている間に、前記磁石が前記シリンジＡ内に配置された撹拌子を前記シリンジＡの外側から動かすことで前記シリンジＡ内の血液を撹拌する、
　駆動装置。
＜１３＞　前記駆動装置と前記微細回路と前記リザーバーと前記シリンジとで、前記リザーバーに蓄えられた血液内の細胞を分級する方法であって、
　予め、
　　前記シリンジＡ内に希釈液と前記撹拌子を配置し、
　　前記シリンジＢ内に押圧液を配置し、
　　前記リザーバーに血液を蓄え、
　　前記微細回路の上面に前記シリンジＢを接続し、
　前記往復機構で、前記シリンジＡの有するピストンＡを引くことで、前記リザーバーから前記シリンジＡ内に血液を取り込み、
　前記装着機構で、前記シリンジＡの前記吐出口を前記微細回路の前記入口に装着し、
　前記撹拌機構で前記シリンジＡ内に配置された撹拌子を前記シリンジＡの外側から動かすことで前記シリンジＡ内の血液と希釈液とを混合撹拌し、
　さらに前記ピストンＡを押すことで前記シリンジＡから前記吐出口及び前記入口を経由して前記微細回路に向かって希釈された血液を連続的に流し入れ、
　さらに前記往復機構が前記ピストンＡを押すのに合わせて、前記押圧機構で前記シリンジＢの有するピストンＢを押すことで前記シリンジＢから前記微細回路に向かって前記押圧液を連続的に流し入れ、
　前記微細回路内で前記シリンジＡが作る血液の流れに対して、その側方より前記シリンジＢが作る押圧液の流れを接触させることで前記血液の流れを反対側に押し込み、
　さらに前記押圧液の流れとは接触していない側にて前記血液の流れの中の細胞を水力学的に分級し、ここで分級される細胞は血球又は血球ではない浮遊細胞である、
　前記微細回路の下面の排出口から分級された細胞を取り出す、
　方法。 <1> A driving device for driving a fluid device.
The fluid device is
A microcircuit for hydraulically classifying cells in blood,
Blood intake and
Syringe A for taking in and storing blood,
A branch connecting the microcircuit, the intake, and the syringe A on three sides,
A syringe B for storing the pressing liquid, which is connected to the microcircuit, and
With
The drive device
The reciprocating mechanism includes a reciprocating mechanism, a pressing mechanism, a stirring mechanism, and a control unit for controlling their coordinated operation. The reciprocating mechanism pulls the piston A of the syringe A from the intake via the branch. Then, blood is taken into the syringe A, and by further pushing the piston A, blood is continuously flowed from the syringe A toward the microcircuit via the branch.
In the pressing mechanism, the pressing liquid is continuously poured from the syringe B toward the microcircuit by pushing the piston B of the syringe B in accordance with the pushing of the piston A by the reciprocating mechanism.
The stirring mechanism has a magnet, and while blood is stored in the syringe A, the magnet moves a stirrer arranged in the syringe A from the outside of the syringe A, thereby causing the syringe. Stir the blood in A,
Drive device.
<2> The driving device further includes a mounting surface on which the reciprocating mechanism and the pressing mechanism are arranged.
The fluid device comprises a flat cartridge that is attached to the attachment surface when classifying cells in blood and is removed from the attachment surface after the blood has been classified.
The microcircuit, the intake, the syringe A, the branch, and the syringe B are arranged in the cartridge.
Upon mounting, the back of the cartridge is oriented so that it faces the mounting surface of the fluid device.
The magnet is arranged so as to face the syringe A and move on the mounting surface.
The drive device according to <1>.
<3> The reciprocating mechanism is a connecting portion A that grips the piston rod of the piston A and an actuator A that reciprocates the connecting portion A along the longitudinal direction of the syringe A and connects to the control unit. And a hold portion for gripping the cylinder of the piston A.
The actuator A is arranged behind the magnet.
The drive device according to <2>.
<4> The magnet is a permanent magnet that reciprocates the stirrer in the syringe A along the longitudinal direction of the syringe A.
The stirring mechanism is an arm that holds the magnet from the side with respect to the reciprocating direction of the magnet, and an actuator M that reciprocates the arm along the longitudinal direction of the syringe A and is connected to the control unit. Further prepare,
The drive device according to <3>.
<5> When the fluid device is attached to the drive device, the syringe A stands with the discharge port down and the piston A up.
The hold portion of the reciprocating mechanism is arranged above the magnet.
The connecting portion A of the reciprocating mechanism is arranged above the holding portion.
The stirring mechanism directs the reciprocating magnet to the lower end of the cylinder of the syringe A.
The drive device according to <4>.
<6> When the control unit starts to take blood into the syringe A, the control unit starts to have the stirring mechanism stir the blood in the syringe A with the magnet.
The drive device according to <1>.
<7> The fluid device is
A first conduit having a side having the intake and a side connecting to the branch,
A second conduit located between the syringe A and the branch,
A third conduit located between the branch and the microcircuit,
With more
The drive device
An intake valve that closes and opens the first conduit,
A start valve that closes and opens the third conduit,
With more
The control unit causes the intake valve to open the first conduit and the start valve to close the third conduit when the reciprocating mechanism pulls the piston A.
The control unit causes the intake valve to close the first conduit and the start valve to open the third conduit when the reciprocating mechanism pushes the piston A.
The drive device according to <1>.
<8> The control unit stores the program of the cooperative operation, and automatically executes the cooperative operation according to a time schedule derived from the program.
The drive device according to <1>.
<9> The drive device according to <1> is provided.
Further comprising the fluid device.
A device for separating cells in the blood.
<10> A method for classifying cells in blood with the separation device according to <9>.
In advance
The diluent and the stirrer are placed in the syringe A.
A pressing liquid is placed in the syringe B,
A blood collection tube that stores blood is attached to the intake,
The branch and the syringe B are connected to the upper surface of the microcircuit, and the branch is connected to the syringe B.
By pulling the piston A of the syringe A with the reciprocating mechanism, blood is taken into the syringe A from the intake via the branch.
By moving the stirrer arranged in the syringe A from the outside of the syringe A by the stirring mechanism, the blood in the syringe A and the diluent are mixed and stirred.
Further, by pushing the piston A, diluted blood is continuously poured from the syringe A toward the microcircuit via the branch.
Further, as the reciprocating mechanism pushes the piston A, the pressing mechanism pushes the piston B of the syringe B to continuously flow the pressing liquid from the syringe B toward the microcircuit.
By contacting the flow of the pressing liquid produced by the syringe B from the side with respect to the blood flow produced by the syringe A in the microcircuit, the blood flow is pushed to the opposite side.
Further, the cells in the blood flow are hydraulically classified on the side not in contact with the flow of the pressing liquid, and the cells classified here are blood cells or floating cells that are not blood cells.
The classified cells are taken out from the outlet on the lower surface of the microcircuit.
Method.
<11> While the drive device is used repeatedly, the fluid device is disposable and replaced.
Classify cells in blood using a clean fluid device for each blood sample,
The method according to <10>.
<12> A drive device for driving a combination of a fine circuit for hydraulically classifying cells in blood, a reservoir for storing pre-classified blood, and a syringe.
The syringe comprises at least a syringe A for taking in and storing blood and a syringe B for storing pressing fluid and connected to another inlet of the microcircuit.
The drive device
A reciprocating mechanism, a mounting mechanism, a pressing mechanism, a stirring mechanism, and a control unit for controlling their cooperative operation are provided. The reciprocating mechanism is provided in the syringe A by pulling the piston A of the syringe A. Takes blood from the reservoir towards
The mounting mechanism mounts the discharge port of the syringe A at the inlet of the microcircuit.
By pushing the piston A, the reciprocating mechanism continuously flows blood from the syringe A toward the microcircuit via the discharge port and the inlet.
In the pressing mechanism, the pressing liquid is continuously poured from the syringe B toward the microcircuit by pushing the piston B of the syringe B in accordance with the pushing of the piston A by the reciprocating mechanism.
The stirring mechanism has a magnet, and while blood is stored in the syringe A, the magnet moves a stirrer arranged in the syringe A from the outside of the syringe A, thereby causing the syringe. Stir the blood in A,
Drive device.
<13> A method of classifying cells in blood stored in the reservoir by the driving device, the microcircuit, the reservoir, and the syringe.
In advance
The diluent and the stirrer are placed in the syringe A.
A pressing liquid is placed in the syringe B,
Blood is stored in the reservoir,
The syringe B is connected to the upper surface of the microcircuit,
By pulling the piston A of the syringe A with the reciprocating mechanism, blood is taken into the syringe A from the reservoir.
With the mounting mechanism, the discharge port of the syringe A is mounted at the inlet of the microcircuit.
By moving the stirrer arranged in the syringe A from the outside of the syringe A by the stirring mechanism, the blood in the syringe A and the diluent are mixed and stirred.
Further, by pushing the piston A, diluted blood is continuously poured from the syringe A toward the microcircuit via the discharge port and the inlet.
Further, as the reciprocating mechanism pushes the piston A, the pressing mechanism pushes the piston B of the syringe B to continuously flow the pressing liquid from the syringe B toward the microcircuit.
By contacting the flow of the pressing liquid produced by the syringe B from the side with respect to the blood flow produced by the syringe A in the microcircuit, the blood flow is pushed to the opposite side.
Further, the cells in the blood flow are hydraulically classified on the side not in contact with the flow of the pressing liquid, and the cells classified here are blood cells or floating cells that are not blood cells.
The classified cells are taken out from the outlet on the lower surface of the microcircuit.
Method.
　本発明により血液中の細胞を水力学的に分級するために微細回路とシリンジとの組み合わせを駆動する装置を提供することができる。 INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide a device that drives a combination of a microcircuit and a syringe in order to classify cells in blood hydraulically.
駆動装置の正面図。Front view of the drive unit. 駆動装置と流体デバイスの使用図。Usage diagram of drive and fluid device. 駆動装置と流体デバイスの使用図。Usage diagram of drive and fluid device. 駆動装置と流体デバイスの使用図。Usage diagram of drive and fluid device. 駆動装置と流体デバイスの斜視図。Perspective view of drive and fluid device. 磁石と往復機構の左側面図。Left side view of magnet and reciprocating mechanism. 撹拌機構とシリンジＡの正面図。Front view of the stirring mechanism and syringe A. 微細回路の平面図。Top view of the microcircuit. 微細回路の部分平面図。Partial plan view of the microcircuit. 微細回路の詳細な部分斜視図。Detailed partial perspective view of the microcircuit. 駆動装置の作動の流れ図。Flow chart of operation of drive device. 駆動装置と流体デバイスの使用図。Usage diagram of drive and fluid device. 制御ユニットの模式図。Schematic diagram of the control unit. 駆動装置の正面図。Front view of the drive unit.
　図１は流体デバイス３０を駆動するための駆動装置７０を示す。説明の便宜のため、図は流体デバイス３０が駆動装置７０から外れた状態を仮想的に表している。図の左側が駆動装置７０を主に表す。図の右側が流体デバイス３０を主に表す。駆動装置７０を説明する前に流体デバイス３０を説明する。 FIG. 1 shows a drive device 70 for driving the fluid device 30. For convenience of explanation, the figure virtually represents a state in which the fluid device 30 is detached from the drive device 70. The left side of the figure mainly represents the drive device 70. The right side of the figure mainly represents the fluid device 30. The fluid device 30 will be described before the drive device 70 is described.
＜１．流体デバイス＞ <1. Fluid device>
　図１の右側に示すように流体デバイス３０は微細回路２０を備える。微細回路は微細な流体回路を備えるチップである。以下、微細回路を符号Ｆ（fine hydraulic circuit）で識別することがある。微細回路２０は微細回路２０に流し込まれた血液中の細胞を水力学的に分級する。 As shown on the right side of FIG. 1, the fluid device 30 includes a microcircuit 20. A fine circuit is a chip having a fine fluid circuit. Hereinafter, the fine circuit may be identified by a reference numeral F (fine hydraulic circuit). The microcircuit 20 hydraulically classifies the cells in the blood poured into the microcircuit 20.
　図１に示すように流体デバイス３０は配管系１０を備える。配管系１０は取入口５０を備える。取入口５０には血液、例えば全血を蓄えた採血管５１が接続される。流体デバイス３０は取入口５０に接続された採血管５１から血液を取り入れる。 As shown in FIG. 1, the fluid device 30 includes a piping system 10. The piping system 10 includes an intake port 50. A blood collection tube 51 that stores blood, for example, whole blood, is connected to the intake port 50. The fluid device 30 takes in blood from the blood collection tube 51 connected to the intake 50.
　図１に示すように流体デバイス３０は血液を蓄えるシリンジＡを備える。以下、シリンジＡ及び関連する部材を符号Ａで識別することがある。シリンジＡの役割を果たすシリンジはシリンジ３５ａである。シリンジ３５ａは血液をシリンジ３５ａ内に取り込むとともに、血液をシリンジ３５ａ内に蓄える。図中ではシリンジ３５ａが希釈血ＤＢを蓄えている。 As shown in FIG. 1, the fluid device 30 includes a syringe A for storing blood. Hereinafter, the syringe A and related members may be identified by reference numeral A. The syringe that serves as the syringe A is the syringe 35a. The syringe 35a takes blood into the syringe 35a and stores the blood in the syringe 35a. In the figure, the syringe 35a stores the diluted blood DB.
　図１に示すようにシリンジ３５ａはピストンＡに当たるピストン３２ａを備える。シリンジ３５ａはさらにシリンダー３４ａを備える。ピストン３２ａはシリンダー３４ａ内を往復する。シリンダー３４ａは吐出口３１ａを有する。シリンダー３４ａはフランジ３６ａを有する。フランジ３６ａは吐出口３１ａの反対側に位置する。シリンダー３４ａ内には撹拌子７５が配置される。シリンジ３５ａはロッド３７ａを有する。ロッド３７ａはシリンジ３５ａのピストンロッドである。ロッド３７ａの一方の端はピストン３２ａに接続する。ロッド３７ａの、ピストン３２ａとは反対の側にフランジ３８ａがある。 As shown in FIG. 1, the syringe 35a includes a piston 32a that hits the piston A. The syringe 35a further comprises a cylinder 34a. The piston 32a reciprocates in the cylinder 34a. The cylinder 34a has a discharge port 31a. The cylinder 34a has a flange 36a. The flange 36a is located on the opposite side of the discharge port 31a. A stirrer 75 is arranged in the cylinder 34a. The syringe 35a has a rod 37a. The rod 37a is a piston rod of the syringe 35a. One end of the rod 37a connects to the piston 32a. There is a flange 38a on the side of the rod 37a opposite to the piston 32a.
　図１に示すように流体デバイス３０は押圧液を蓄えるシリンジＢをさらに備える。以下、シリンジＢ及び関連する部材を符号Ｂで識別することがある。シリンジＢの役割を果たすシリンジはシリンジ３５ｂである。シリンジ３５ｂは押圧液ＰＬを蓄える。第２シリンジ３５ｂは第４導管１２を介して微細回路２０に接続する。 As shown in FIG. 1, the fluid device 30 further includes a syringe B for storing the pressing liquid. Hereinafter, the syringe B and related members may be identified by reference numeral B. The syringe that plays the role of syringe B is syringe 35b. The syringe 35b stores the pressing liquid PL. The second syringe 35b is connected to the microcircuit 20 via the fourth conduit 12.
　図１に示すようにシリンジ３５ｂはピストンＢに当たるピストン３２ｂを備える。シリンジ３５ｂはさらにシリンダー３４ｂを備える。ピストン３２ｂはシリンダー３４ｂ内を往復する。シリンダー３４ｂは吐出口３１ｂを有する。シリンダー３４ｂはフランジ３６ｂを有する。フランジ３６ｂは吐出口３１ｂの反対側に位置する。シリンジ３５ｂはロッド３７ｂを有する。ロッド３７ｂはシリンジ３５ｂのピストンロッドである。ロッド３７ｂの一方の端はピストン３２ｂに接続する。ロッド３７ｂの、ピストン３２ｂとは反対の側にフランジ３８ｂがある。 As shown in FIG. 1, the syringe 35b includes a piston 32b that hits the piston B. The syringe 35b further comprises a cylinder 34b. The piston 32b reciprocates in the cylinder 34b. The cylinder 34b has a discharge port 31b. The cylinder 34b has a flange 36b. The flange 36b is located on the opposite side of the discharge port 31b. The syringe 35b has a rod 37b. The rod 37b is a piston rod of the syringe 35b. One end of the rod 37b connects to the piston 32b. There is a flange 38b on the side of the rod 37b opposite to the piston 32b.
　図１に示すように配管系１０は第１導管１１ａ、第２導管１１ｂ、第３導管１１ｃ、第４導管１２及び分岐１５を備える。分岐１５は微細回路２０、取入口５０及びシリンジ３５ａからなる三方の間を連絡する。 As shown in FIG. 1, the piping system 10 includes a first conduit 11a, a second conduit 11b, a third conduit 11c, a fourth conduit 12, and a branch 15. The branch 15 communicates between the microcircuit 20, the intake 50 and the syringe 35a on three sides.
　図１に示すように第１導管１１ａは取入口５０を有する側の末端と分岐１５に接続する側の末端とを有する。第２導管１１ｂはシリンジ３５ａと分岐１５との間に位置する。第３導管１１ｃは分岐１５と微細回路２０との間に位置する。 As shown in FIG. 1, the first conduit 11a has an end on the side having the intake 50 and an end on the side connecting to the branch 15. The second conduit 11b is located between the syringe 35a and the branch 15. The third conduit 11c is located between the branch 15 and the microcircuit 20.
　図１に示すように第２導管１１ｂはシリンジ３５ａと分岐１５との間に位置する。第２導管１１ｂの一方の端は吐出口３１ａと接続する。第２導管１１ｂのもう一方の端は分岐１５に接続する。 As shown in FIG. 1, the second conduit 11b is located between the syringe 35a and the branch 15. One end of the second conduit 11b is connected to the discharge port 31a. The other end of the second conduit 11b connects to the branch 15.
　図１に示すように第３導管１１ｃは分岐１５と微細回路２０との間に位置する。第３導管１１ｃの一方の端は分岐１５に接続する。第３導管１１ｃのもう一方の端は微細回路２０に接続する。 As shown in FIG. 1, the third conduit 11c is located between the branch 15 and the microcircuit 20. One end of the third conduit 11c connects to the branch 15. The other end of the third conduit 11c connects to the microcircuit 20.
　図１に示すように第４導管１２はシリンジ３５ｂと微細回路２０との間に位置する。第４導管１２の一方の端は吐出口３１ｂに接続する。第４導管１２のもう一方の端は微細回路２０に接続する。 As shown in FIG. 1, the fourth conduit 12 is located between the syringe 35b and the microcircuit 20. One end of the fourth conduit 12 is connected to the discharge port 31b. The other end of the fourth conduit 12 connects to the microcircuit 20.
　図１には示すように採血管５１はキャップ５２を有する。キャップ５２はゴム栓でもよい。通気針５３を採血管５１に取り付けてもよい。通気針５３はキャップ５２を貫通する。採血管５１の内腔に採血管５１の外部の空気を導く。採血管５１は採血管ホルダー５４内に収容される。取入口５０は採血管ホルダー５４を介して採血管５１と接続されてもよい。 As shown in FIG. 1, the blood collection tube 51 has a cap 52. The cap 52 may be a rubber stopper. The ventilation needle 53 may be attached to the blood collection tube 51. The ventilation needle 53 penetrates the cap 52. The air outside the blood collection tube 51 is guided to the lumen of the blood collection tube 51. The blood collection tube 51 is housed in the blood collection tube holder 54. The intake 50 may be connected to the blood collection tube 51 via the blood collection tube holder 54.
　図１に示すように駆動装置７０と流体デバイス３０とを組み合わせることで一体の分離装置とすることができる。駆動装置７０を備える分離装置は、標的とする細胞を血液内の他の細胞又は成分から分離する。 As shown in FIG. 1, the drive device 70 and the fluid device 30 can be combined to form an integrated separation device. A separator with a drive device 70 separates the target cell from other cells or components in the blood.
＜２．駆動装置＞ <2. Drive>
　図１に示すように、駆動装置７０は、往復機構７１ａと、押圧機構７１ｂと、撹拌機構７１ｃとを備える。駆動装置７０はさらに、これらの協調動作を制御する制御ユニット８０を備える。 As shown in FIG. 1, the drive device 70 includes a reciprocating mechanism 71a, a pressing mechanism 71b, and a stirring mechanism 71c. The drive device 70 further includes a control unit 80 that controls these coordinated operations.
　図１に示すように往復機構７１ａは連結部Ａに当たる把持部７２ａを備える。往復機構７１ａはさらにアクチュエーターＡに当たるアクチュエーター７３ａを備える。往復機構７１ａはシリンジＡに関連するので、以下、往復機構を符号Ａで識別することがある。 As shown in FIG. 1, the reciprocating mechanism 71a includes a grip portion 72a that corresponds to the connecting portion A. The reciprocating mechanism 71a further includes an actuator 73a that corresponds to the actuator A. Since the reciprocating mechanism 71a is related to the syringe A, the reciprocating mechanism may be identified by the reference numeral A below.
　図１に示すように押圧機構７１ｂは把持部７２ｂを備える。押圧機構７１ｂはさらにアクチュエーター７３ｂを備える。押圧機構７１ｂはシリンジＢに関連するので、以下、押圧機構を符号Ｂで識別することがある。 As shown in FIG. 1, the pressing mechanism 71b includes a grip portion 72b. The pressing mechanism 71b further includes an actuator 73b. Since the pressing mechanism 71b is related to the syringe B, the pressing mechanism may be identified by the reference numeral B below.
　図１に示すように撹拌機構７１ｃはアーム７２ｃと、アクチュエーターＭに当たるアクチュエーター７３ｃと、磁石７４とを備える。以下、撹拌機構７１ｃを符号Ｍ（mixing）で識別することがある。 As shown in FIG. 1, the stirring mechanism 71c includes an arm 72c, an actuator 73c corresponding to the actuator M, and a magnet 74. Hereinafter, the stirring mechanism 71c may be identified by a reference numeral M (mixing).
　図１に示すようにアーム７２ｃは磁石７４を保持する。アクチュエーター７３ｃはアーム７２ｃを介して磁石７４を動かす。撹拌機構７１ｃが磁石７４を動かす態様はこれに限定されない。磁石７４は永久磁石又は電磁石でもよい。 As shown in FIG. 1, the arm 72c holds the magnet 74. The actuator 73c moves the magnet 74 via the arm 72c. The mode in which the stirring mechanism 71c moves the magnet 74 is not limited to this. The magnet 74 may be a permanent magnet or an electromagnet.
　図１において撹拌機構７１ｃは撹拌子７５でシリンダー３４ａ内の希釈血ＤＢを撹拌する。撹拌子７５は強磁性体を有する。磁石７４の磁力が撹拌子７５に影響を及ぼす。シリンダー３４ａ内に希釈血ＤＢとして血液が蓄えられている間に、磁石７４が撹拌子７５を動かす。撹拌により希釈前の血液と希釈液とがよく混合される。さらに撹拌機構７１ｃが希釈血ＤＢを撹拌し続けることで希釈血ＤＢ中の血球又は血球ではない浮遊細胞の沈殿を抑制できる。 In FIG. 1, the stirring mechanism 71c stirs the diluted blood DB in the cylinder 34a with the stirrer 75. The stirrer 75 has a ferromagnet. The magnetic force of the magnet 74 affects the stirrer 75. The magnet 74 moves the stirrer 75 while blood is stored in the cylinder 34a as the diluted blood DB. By stirring, the blood before dilution and the diluted solution are well mixed. Further, the stirring mechanism 71c can continuously stir the diluted blood DB to suppress the precipitation of blood cells or floating cells that are not blood cells in the diluted blood DB.
　図１において制御ユニット８０はアクチュエーター７３ａ、アクチュエーター７３ｂ及びアクチュエーター７３ｃと接続する。制御ユニット８０はこれらのアクチュエーターを介して撹拌機構７１ｃを往復機構７１ａ及び押圧機構７１ｂと協調動作させる。 In FIG. 1, the control unit 80 is connected to the actuator 73a, the actuator 73b, and the actuator 73c. The control unit 80 causes the stirring mechanism 71c to cooperate with the reciprocating mechanism 71a and the pressing mechanism 71b via these actuators.
　図１に示すように駆動装置７０は取入バルブ７６ａと開始バルブ７６ｂとを備える。制御ユニット８０はこれらのバルブと接続する。制御ユニット８０による制御の下、取入バルブ７６ａは第１導管１１ａを閉鎖及び開放することができる。制御ユニット８０による制御の下、開始バルブ７６ｂは第３導管１１ｃを閉鎖及び開放することができる。 As shown in FIG. 1, the drive device 70 includes an intake valve 76a and a start valve 76b. The control unit 80 connects to these valves. Under the control of the control unit 80, the intake valve 76a can close and open the first conduit 11a. Under control by the control unit 80, the start valve 76b can close and open the third conduit 11c.
＜３．組み合わせ＞ <3. Combination>
　図２～図４は、駆動装置７０を使用して流体デバイス３０を動作させる様子が示されている。まず図２を用いて駆動装置７０と流体デバイス３０とがどのように組み合わせられるのか説明する。 2 to 4 show how the fluid device 30 is operated by using the drive device 70. First, how the drive device 70 and the fluid device 30 are combined will be described with reference to FIG.
　図２は血液ＢＬをシリンジ３５ａに取り込む様子を示している。まず往復機構７１ａとシリンジ３５ａとの関係を説明する。把持部７２ａはフランジ３８ａを把持する。往復機構７１ａとシリンジ３５ａとの連結の態様はこれに限定されない。把持部７２ａはアクチュエーター７３ａに接続する。把持部７２ａはアクチュエーター７３ａの力をフランジ３８ａに伝えることで、ロッド３７ａを介して、ピストン３２ａを図中の上下に移動させることができる。 FIG. 2 shows how the blood BL is taken into the syringe 35a. First, the relationship between the reciprocating mechanism 71a and the syringe 35a will be described. The grip portion 72a grips the flange 38a. The mode of connection between the reciprocating mechanism 71a and the syringe 35a is not limited to this. The grip portion 72a is connected to the actuator 73a. By transmitting the force of the actuator 73a to the flange 38a, the grip portion 72a can move the piston 32a up and down in the drawing via the rod 37a.
　さらに押圧機構７１ｂとシリンジ３５ｂとの関係を説明する。図２に示すように把持部７２ｂはフランジ３８ｂを把持する。押圧機構７１ｂとシリンジ３５ｂとの連結の態様はこれに限定されない。把持部７２ｂはアクチュエーター７３ｂに接続する。把持部７２ｂはアクチュエーター７３ｂの力をフランジ３８ｂに伝えることで、ロッド３７ｂを介して、ピストン３２ｂを下方に移動させることができる。把持部７２ｂはさらにピストン３２ｂを上方に移動させるものであってもよい。 Further, the relationship between the pressing mechanism 71b and the syringe 35b will be described. As shown in FIG. 2, the grip portion 72b grips the flange 38b. The mode of connection between the pressing mechanism 71b and the syringe 35b is not limited to this. The grip portion 72b is connected to the actuator 73b. By transmitting the force of the actuator 73b to the flange 38b, the grip portion 72b can move the piston 32b downward via the rod 37b. The grip portion 72b may further move the piston 32b upward.
　図２に示すように微細回路２０は入口２１ａ及び入口２１ｂを備える。微細回路２０はさらに出口２２ａ、出口２２ｂ及び出口２２ｃを備える。微細回路２０の構造と機能の詳細は後述する。 As shown in FIG. 2, the microcircuit 20 includes an inlet 21a and an inlet 21b. The microcircuit 20 further includes an outlet 22a, an outlet 22b, and an outlet 22c. Details of the structure and function of the microcircuit 20 will be described later.
＜４．駆動装置の動作＞ <4. Operation of drive unit>
　図２に示すように制御ユニット８０は、往復機構７１ａにロッド３７ａとフランジ３８ａとを介してピストン３２ａを引かせる。この時に、制御ユニット８０は、取入バルブ７６ａに第１導管１１ａを開放させる。制御ユニット８０は、この時さらに開始バルブ７６ｂに第３導管１１ｃを閉鎖させる。 As shown in FIG. 2, the control unit 80 causes the reciprocating mechanism 71a to pull the piston 32a via the rod 37a and the flange 38a. At this time, the control unit 80 causes the intake valve 76a to open the first conduit 11a. The control unit 80 further closes the third conduit 11c to the start valve 76b at this time.
　図２において往復機構７１ａは取入口５０から分岐１５を経由してシリンジ３５ａの有するシリンダー３４ａ内に血液ＢＬを取り込む。取入口５０には採血管５１が取り付けられている。採血管５１は採取された血液ＢＬを予め蓄えている。採血管５１は真空採血管でもよい。血液ＢＬは未希釈の全血でもよい。採血管５１に予め試薬を添加しておき、事前に未希釈の全血とこれを混合しておいてもよい。 In FIG. 2, the reciprocating mechanism 71a takes in blood BL from the intake port 50 via the branch 15 into the cylinder 34a of the syringe 35a. A blood collection tube 51 is attached to the intake port 50. The blood collection tube 51 stores the collected blood BL in advance. The blood collection tube 51 may be a vacuum blood collection tube. Blood BL may be undiluted whole blood. A reagent may be added to the blood collection tube 51 in advance and mixed with undiluted whole blood in advance.
　図２に示すようにシリンダー３４ａは予め希釈液ＤＬを蓄えている。血液ＢＬがシリンダー３４ａ内に取り込まれる際、希釈液ＤＬによって血液ＢＬがシリンダー３４ａ内で希釈される。シリンダー３４ａ内には撹拌子７５が予め配置されている。制御ユニット８０の制御の下、撹拌機構（Ｍ）の磁石７４が撹拌子７５を動かしてもよい。磁石７４が希釈液ＤＬと血液ＢＬとを混合してもよい。 As shown in FIG. 2, the cylinder 34a stores the diluent DL in advance. When the blood BL is taken into the cylinder 34a, the diluent DL dilutes the blood BL in the cylinder 34a. A stirrer 75 is arranged in advance in the cylinder 34a. Under the control of the control unit 80, the magnet 74 of the stirring mechanism (M) may move the stirrer 75. The magnet 74 may mix the diluent DL and the blood BL.
　図３は、血液ＢＬをシリンジ３５ａに取り込み終えた様子が示されている。制御ユニット８０は、往復機構７１ａに対して、ピストン３２ａを引く動作を止めさせる。制御ユニット８０の制御の下、撹拌機構（Ｍ）は磁石７４を介して撹拌子７５を動かす。この動きは図２から引き続き行ってもよい。撹拌子７５はシリンダー３４ａ内の液体をよく混合する。希釈液と血液ＢＬとの混合によりシリンダー３４ａ内に希釈血ＤＢが得られる。また撹拌が希釈血ＤＢ中の血球の沈降を抑制する。 FIG. 3 shows how the blood BL has been taken into the syringe 35a. The control unit 80 causes the reciprocating mechanism 71a to stop the operation of pulling the piston 32a. Under the control of the control unit 80, the stirring mechanism (M) moves the stirrer 75 via the magnet 74. This movement may be continued from FIG. The stir bar 75 mixes the liquid in the cylinder 34a well. Diluted blood DB is obtained in the cylinder 34a by mixing the diluted solution and blood BL. Stirring also suppresses the sedimentation of blood cells in the diluted blood DB.
　図４は、希釈血ＤＢを微細回路２０に流し入れる様子が示されている。制御ユニット８０は、往復機構７１ａにロッド３７ａとフランジ３８ａとを介してピストン３２ａを押させる。この時に、制御ユニット８０は、取入バルブ７６ａに第１導管１１ａを閉鎖させる。制御ユニット８０は、この時さらに開始バルブ７６ｂに第３導管１１ｃを開放させる。 FIG. 4 shows how the diluted blood DB is poured into the fine circuit 20. The control unit 80 causes the reciprocating mechanism 71a to push the piston 32a via the rod 37a and the flange 38a. At this time, the control unit 80 closes the first conduit 11a to the intake valve 76a. At this time, the control unit 80 further opens the third conduit 11c to the start valve 76b.
　図４に示すように、制御ユニット８０は、さらに押圧機構７１ｂにピストン３２ｂを押させる。押圧機構７１ｂは往復機構７１ａがピストン３２ａを押すのに合わせてこれを行う。シリンジ３５ｂの有するシリンダー３４ｂは予め押圧液ＰＬを蓄えている。微細回路２０内での押圧液ＰＬの働きは後述する。 As shown in FIG. 4, the control unit 80 further causes the pressing mechanism 71b to push the piston 32b. The pressing mechanism 71b does this as the reciprocating mechanism 71a pushes the piston 32a. The cylinder 34b of the syringe 35b stores the pressing liquid PL in advance. The function of the pressing liquid PL in the fine circuit 20 will be described later.
　図４において、往復機構７１ａはシリンジ３５ａから分岐１５を経由して微細回路２０に向かって希釈血ＤＢを連続的に流し入れる。押圧機構７１ｂはシリンダー３４ｂから微細回路２０に向かって押圧液ＰＬを連続的に流し入れる。シリンダー３４ａから希釈血ＤＢが、さらにシリンダー３４ｂから押圧液ＰＬが、互いに並行して微細回路２０に流れ込む。 In FIG. 4, the reciprocating mechanism 71a continuously flows the diluted blood DB from the syringe 35a toward the microcircuit 20 via the branch 15. The pressing mechanism 71b continuously flows the pressing liquid PL from the cylinder 34b toward the fine circuit 20. The diluted blood DB flows from the cylinder 34a, and the pressing liquid PL flows from the cylinder 34b into the microcircuit 20 in parallel with each other.
　図４において制御ユニット８０の制御の下、撹拌機構（Ｍ）は磁石７４を介して撹拌子７５を動かす。この動きは図３から引き続き行ってもよい。撹拌子７５は希釈血ＤＢをよく撹拌する。撹拌が希釈血ＤＢ中の血球の沈降を抑制する。これにより希釈血ＤＢ中の単位体積当たりの血球数が均一化される。シリンジ３５ａはこのように均一化された希釈血ＤＢを微細回路２０に送り込むことができる。希釈血ＤＢを微細回路２０に送り込む間、時間帯によって単位体積当たりの血球数の変動することが抑制される。 In FIG. 4, under the control of the control unit 80, the stirring mechanism (M) moves the stirrer 75 via the magnet 74. This movement may be continued from FIG. The stirrer 75 stirs the diluted blood DB well. Stirring suppresses the sedimentation of blood cells in the diluted blood DB. As a result, the number of blood cells per unit volume in the diluted blood DB is made uniform. The syringe 35a can send the diluted blood DB thus homogenized to the microcircuit 20. While the diluted blood DB is sent to the microcircuit 20, fluctuation of the number of blood cells per unit volume is suppressed depending on the time zone.
　さらにピストン３２ａとピストン３２ｂとは、制御ユニット８０による制御の下、協調的に動作する。これらが希釈血ＤＢと押圧液ＰＬとを微細回路２０に送り込む。制御ユニット８０による制御の下、ピストン３２ａと撹拌子７５とピストン３２ｂとが協調して動作する。 Further, the piston 32a and the piston 32b operate cooperatively under the control of the control unit 80. These feed the diluted blood DB and the pressing liquid PL into the microcircuit 20. Under the control of the control unit 80, the piston 32a, the stirrer 75, and the piston 32b operate in cooperation with each other.
　また図２から図４を用いて説明した通りピストン３２ａと取入バルブ７６ａと開始バルブ７６ｂとは、制御ユニットによる制御の下、協調的に動作する。これらがいわばポンプとして動作することで採血管５１中の血液ＢＬを微細回路２０に送り込む。先の３つの要素に加えて２つのバルブがさらに協調動作することが好ましい。 Further, as described with reference to FIGS. 2 to 4, the piston 32a, the intake valve 76a, and the start valve 76b operate cooperatively under the control of the control unit. By operating as a so-called pump, the blood BL in the blood collection tube 51 is sent to the microcircuit 20. It is preferable that the two valves cooperate further in addition to the above three elements.
　変形例として取入バルブ７６ａ及び開始バルブ７６ｂの少なくともいずれかを逆止弁に置き換えてもよい。またこれらのバルブを分岐１５に設置される三方活栓に置き換えてもよい。 As a modification, at least one of the intake valve 76a and the start valve 76b may be replaced with a check valve. Further, these valves may be replaced with a three-way stopcock installed at the branch 15.
　以下に実施例を参照しながら、上記実施形態に係る駆動装置の具体的な態様を示す。さらに上記実施形態に係る駆動装置の利用を説明する。以下の実施例は本発明のスコープを限定するものではない。 The specific aspects of the drive device according to the above embodiment are shown below with reference to the examples. Further, the use of the drive device according to the above embodiment will be described. The following examples do not limit the scope of the present invention.
＜５．流体デバイスのカートリッジ形態＞ <5. Fluid device cartridge form>
　図５はカートリッジ形態をとる流体デバイス３０とこれに合わせて作られた駆動装置７０とを示す。駆動装置７０は取り付け面８６をさらに備える。取り付け面８６には往復機構７１ａと、押圧機構７１ｂとが配置されている。駆動装置７０はさらにガイド８７ａ及び８７ｂを備えていてもよい。ガイド８７ａ及び８７ｂは取り付け面８６上に配置されていてもよい。 FIG. 5 shows a fluid device 30 in the form of a cartridge and a drive device 70 made in accordance with the fluid device 30. The drive device 70 further includes a mounting surface 86. A reciprocating mechanism 71a and a pressing mechanism 71b are arranged on the mounting surface 86. The drive device 70 may further include guides 87a and 87b. The guides 87a and 87b may be arranged on the mounting surface 86.
　図５に示すように本実施例では流体デバイス３０は平板状のカートリッジからなる。流体デバイス３０は血液中の細胞を分級する時に取り付け面８６に装着される。カバーによって取り付け面８６と流体デバイス３０とをさらに覆ってもよい。血液の分級を終えた後に流体デバイス３０は取り付け面８６から取り外される。 As shown in FIG. 5, in this embodiment, the fluid device 30 is composed of a flat plate cartridge. The fluid device 30 is attached to the mounting surface 86 when classifying cells in blood. A cover may further cover the mounting surface 86 and the fluid device 30. After finishing the classification of blood, the fluid device 30 is removed from the mounting surface 86.
　図５に示すように流体デバイス３０を構成するカートリッジの中に、微細回路２０と、取入口５０と、シリンジＡに当たるシリンジ３５ａと、分岐１５と、シリンジＢに当たるシリンジ３５ｂとが平面的に配置している。これらの部材はケース５５によってその位置を固定されている。 As shown in FIG. 5, the microcircuit 20, the intake port 50, the syringe 35a corresponding to the syringe A, the branch 15 and the syringe 35b corresponding to the syringe B are arranged in a plane in the cartridge constituting the fluid device 30. ing. The positions of these members are fixed by the case 55.
　図５において流体デバイス３０を駆動装置７０に装着する。この際、カートリッジ状の流体デバイス３０の背面が、取り付け面８６に対向するように向く。ガイド８７ａ及び８７ｂはカートリッジ状の流体デバイス３０の底部を受け止める。 In FIG. 5, the fluid device 30 is attached to the drive device 70. At this time, the back surface of the cartridge-shaped fluid device 30 faces the mounting surface 86. The guides 87a and 87b receive the bottom of the cartridge-like fluid device 30.
　図５は装着後の各シリンジと駆動装置７０との位置関係も示している。ホールド部７９ａはシリンダー３４ａを把持する。把持部７２ａはフランジ３８ａを把持する。またホールド部７９ｂはシリンダー３４ｂを把持する。把持部７２ｂはフランジ３８ｂを把持する。ガイド８７ａ及び８７ｂがカートリッジ状の流体デバイス３０の取り付け高さを規定することで、部材の高さを揃える。 FIG. 5 also shows the positional relationship between each syringe and the drive device 70 after mounting. The hold portion 79a grips the cylinder 34a. The grip portion 72a grips the flange 38a. Further, the hold portion 79b grips the cylinder 34b. The grip portion 72b grips the flange 38b. The guides 87a and 87b define the mounting height of the cartridge-shaped fluid device 30, thereby aligning the heights of the members.
　図５に示すようにホールド部７９ａは支持器７８ａを備える。支持器７８ａはフランジ３６ａの下面を支えることで、シリンダー３４ａが落下しないように支える。支持器７８ａはシリンダー３４ａの左右両側でフランジ３６ａの下面を支えることが好ましい。さらに支持器７８ａはシリンダー３４ａが図中の左右方向に移動しないように拘束する。 As shown in FIG. 5, the hold portion 79a includes a support 78a. The support 78a supports the lower surface of the flange 36a so that the cylinder 34a does not fall. The support 78a preferably supports the lower surface of the flange 36a on both the left and right sides of the cylinder 34a. Further, the support 78a restrains the cylinder 34a so as not to move in the left-right direction in the drawing.
　図５に示すようにホールド部７９ａは押さえ具７７ａをさらに備える。押さえ具７７ａはフランジ３６ａの上面を押さえることで、シリンダー３４ａが支持器７８ａから飛び出さないようにシリンダー３４ａを拘束する。特に往復機構７１ａによってシリンダー３４ａからピストン３２ａが引かれる際に、押さえ具７７ａがシリンダー３４ａを押さえる。 As shown in FIG. 5, the hold portion 79a further includes a holding tool 77a. The presser 77a presses the upper surface of the flange 36a to restrain the cylinder 34a so that the cylinder 34a does not protrude from the support 78a. In particular, when the piston 32a is pulled from the cylinder 34a by the reciprocating mechanism 71a, the presser 77a presses the cylinder 34a.
　図５に示すようにフランジ３６ａは押さえ具７７ａの下面と支持器７８ａの上面とによって挟まれる。押さえ具７７ａはシリンダー３４ａに挿入されたピストン３２ａの左右両側でフランジ３６ａの上面を押さえることが好ましい。シリンダー３４ａの左右両側で、押さえ具７７ａの下面と支持器７８ａの上面とがフランジ３６ａを挟み込むことが好ましい。 As shown in FIG. 5, the flange 36a is sandwiched between the lower surface of the holding tool 77a and the upper surface of the support 78a. The presser 77a preferably presses the upper surface of the flange 36a on both the left and right sides of the piston 32a inserted into the cylinder 34a. It is preferable that the lower surface of the holding tool 77a and the upper surface of the support 78a sandwich the flange 36a on both the left and right sides of the cylinder 34a.
　図５に示すようにホールド部７９ｂは支持器７８ｂを備える。支持器７８ｂはフランジ３６ｂの下面を支えることで、シリンダー３４ｂが落下しないように支える。支持器７８ｂはシリンダー３４ｂの左右両側でフランジ３６ｂの下面を支えることが好ましい。さらに支持器７８ｂはシリンダー３４ｂが図中の左右方向に移動しないように拘束する。 As shown in FIG. 5, the hold portion 79b includes a support 78b. The support 78b supports the lower surface of the flange 36b so that the cylinder 34b does not fall. The support 78b preferably supports the lower surface of the flange 36b on both the left and right sides of the cylinder 34b. Further, the support 78b restrains the cylinder 34b so as not to move in the left-right direction in the drawing.
　図５に示すようにホールド部７９ｂは押さえ具７７ｂをさらに備える。押さえ具７７ｂはフランジ３６ｂの上面を押さえることで、シリンダー３４ｂが支持器７８ｂから飛び出さないようにシリンダー３４ｂを拘束可能なものであってもよい。特に押圧機構７２ｂによってシリンダー３４ｂからピストン３２ｂが引き抜かれる際に、押さえ具７７ｂがシリンダー３４ｂを押さえることが可能であってもよい。 As shown in FIG. 5, the hold portion 79b further includes a holding tool 77b. The holding tool 77b may be capable of restraining the cylinder 34b so that the cylinder 34b does not protrude from the support 78b by pressing the upper surface of the flange 36b. In particular, when the piston 32b is pulled out from the cylinder 34b by the pressing mechanism 72b, the pressing tool 77b may be able to press the cylinder 34b.
　図５に示すようにフランジ３６ｂは押さえ具７７ｂの下面と支持器７８ｂの上面とによって挟まれる。押さえ具７７ｂはシリンダー３４ｂに挿入されたピストン３２ｂの左右両側でフランジ３６ｂの上面を押さえるものであってもよい。シリンダー３４ｂの左右両側で、押さえ具７７ｂの下面と支持器７８ｂの上面とがフランジ３６ｂを挟み込んでもよい。 As shown in FIG. 5, the flange 36b is sandwiched between the lower surface of the holding tool 77b and the upper surface of the support 78b. The presser 77b may press the upper surface of the flange 36b on both the left and right sides of the piston 32b inserted into the cylinder 34b. On both the left and right sides of the cylinder 34b, the lower surface of the presser foot 77b and the upper surface of the support 78b may sandwich the flange 36b.
　図５に示すように磁石７４はシリンダー３４ａに対向する。磁石７４は取り付け面８６上を移動するように配置している。磁石７４は動作エリアＯＡ内を往復運動する。動作エリアＯＡは取り付け面８６上に設けられた貫通孔やくぼみで形成されていてもよい。図中では動作エリアＯＡは貫通孔となっている。 As shown in FIG. 5, the magnet 74 faces the cylinder 34a. The magnet 74 is arranged so as to move on the mounting surface 86. The magnet 74 reciprocates in the operating area OA. The operating area OA may be formed by a through hole or a recess provided on the mounting surface 86. In the figure, the operating area OA is a through hole.
　図５に示すように平板状の流体デバイス３０の背面を取り付け面８６に接近させることで、磁石７４をシリンダー３４ａに近づけることができる。このため磁石７４の磁力はシリンダー３４ａ内の撹拌子７５に効率的に伝わる。 As shown in FIG. 5, the magnet 74 can be brought closer to the cylinder 34a by bringing the back surface of the flat plate-shaped fluid device 30 closer to the mounting surface 86. Therefore, the magnetic force of the magnet 74 is efficiently transmitted to the stirrer 75 in the cylinder 34a.
　図５に示すようにケース５５はアクセス窓５９を有する。取入バルブ７６ａはアクセス窓８９を通って第１導管１１ａに到達する。取入バルブ７６ａが第１導管１１ａを捉える。取入バルブ７６ａは第１導管１１ａを押しつぶすことで第１導管１１ａ内を閉鎖する。取入バルブ７６ａは第１導管１１ａを押しつぶすことを止めることで第１導管１１ａ内を開放する。 As shown in FIG. 5, the case 55 has an access window 59. The intake valve 76a reaches the first conduit 11a through the access window 89. The intake valve 76a catches the first conduit 11a. The intake valve 76a closes the inside of the first conduit 11a by crushing the first conduit 11a. The intake valve 76a opens the inside of the first conduit 11a by stopping crushing the first conduit 11a.
　図５に示すように開始バルブ７６ｂはアクセス窓５９を通って第３導管１１ｃに到達する。開始バルブ７６ｂが第３導管１１ｃを捉える。開始バルブ７６ｂは第３導管１１ｃを押しつぶすことで第３導管１１ｃ内を閉塞する。開始バルブ７６ｂは第３導管１１ｃを押しつぶすことを止めることで第３導管１１ｃ内を開放する。 As shown in FIG. 5, the start valve 76b reaches the third conduit 11c through the access window 59. The start valve 76b catches the third conduit 11c. The start valve 76b closes the inside of the third conduit 11c by crushing the third conduit 11c. The start valve 76b opens the inside of the third conduit 11c by stopping crushing the third conduit 11c.
　図５に示すようにカートリッジ形態をとる流体デバイス３０は採取容器５６及び排液容器５７をさらに備えている。採取容器５６は微細回路２０で分級された目的の細胞、例えば有核の血球を受け入れる。排液容器５７は、分級作業で生じた、細胞を含まない画分や目的外の細胞を受け入れる。採取容器５６及び排液容器５７はケース５５内に配置される。採取容器５６はケース５５から取り出すことができる。排液容器５７はケース５５内に封入されていてもよい。 As shown in FIG. 5, the fluid device 30 in the form of a cartridge further includes a collection container 56 and a drainage container 57. The collection vessel 56 receives cells of interest classified by the microcircuit 20, such as nucleated blood cells. The drainage container 57 receives cell-free fractions and unintended cells generated by the classification operation. The collection container 56 and the drainage container 57 are arranged in the case 55. The collection container 56 can be taken out from the case 55. The drainage container 57 may be enclosed in the case 55.
　図５に例示するように、駆動装置７０の各構成要素は流体デバイス３０とは分離している。分級に必要な流体回路は流体デバイス３０に搭載されている。一例において駆動装置７０内には流体デバイス３０の構成要素は含まれていない。駆動装置７０は流体デバイス３０に対して分級に必要な動力を提供する。 As illustrated in FIG. 5, each component of the drive device 70 is separated from the fluid device 30. The fluid circuit required for classification is mounted on the fluid device 30. In one example, the drive device 70 does not include the components of the fluid device 30. The drive device 70 provides the fluid device 30 with the power required for classification.
　図５に示すように分級が必要になるたびに流体デバイス３０をカートリッジとして駆動装置７０に取り付けることができる。また分級後の流体デバイス３０は駆動装置７０から取り外して廃棄することができる。 As shown in FIG. 5, the fluid device 30 can be attached to the drive device 70 as a cartridge each time classification is required. Further, the fluid device 30 after classification can be removed from the drive device 70 and discarded.
　図５において、分級作業一回ごとに流体デバイス３０を使い捨て交換してもよい。一方で駆動装置７０は繰り返し使用してもよい。これにより血液のサンプルごとにクリーンな流体デバイス３０を用いて血液内の細胞を分級することができる。撹拌子７５も流体デバイス３０とともに使い捨て交換してもよい。 In FIG. 5, the fluid device 30 may be disposablely replaced for each classification operation. On the other hand, the drive device 70 may be used repeatedly. This allows cells in the blood to be classified using a clean fluid device 30 for each blood sample. The stir bar 75 may also be disposable and replaced with the fluid device 30.
　図５において駆動装置７０は各シリンジや微細回路２０から独立したものである。したがって駆動装置７０には血液試料が付着しにくい。これにより駆動装置７０が相異なる血液試料間のコンタミネーションを媒介することが抑制されている。 In FIG. 5, the drive device 70 is independent of each syringe and the microcircuit 20. Therefore, the blood sample is unlikely to adhere to the drive device 70. This prevents the drive device 70 from mediating contamination between different blood samples.
＜６．磁石と往復機構の配置＞ <6. Arrangement of magnet and reciprocating mechanism>
　図６は図５に示すＶＩ断面で観察した磁石７４と往復機構７１ａとを表す。本図においてカートリッジ状の流体デバイスは駆動装置にすでに取り付けられているものとする。図中においてカートリッジのケースは省略されている。 FIG. 6 shows the magnet 74 and the reciprocating mechanism 71a observed in the VI cross section shown in FIG. In this figure, it is assumed that the cartridge-shaped fluid device is already attached to the drive device. The cartridge case is omitted in the figure.
　図６に示すように磁石７４の後ろ側にアクチュエーター７３ａが配置されている。ここで後ろ側とは磁石７４を挟んでシリンダー３４ａとは反対側にアクチュエーター７３ａが位置するという意味である。アクチュエーター７３ａは把持部７２ａをシリンジ３５ａの長手方向に沿って往復運動させる。アクチュエーター７３ａは磁石７４の後ろ側からロッド３７ａを動かす。 As shown in FIG. 6, the actuator 73a is arranged behind the magnet 74. Here, the rear side means that the actuator 73a is located on the side opposite to the cylinder 34a with the magnet 74 in between. The actuator 73a reciprocates the grip portion 72a along the longitudinal direction of the syringe 35a. The actuator 73a moves the rod 37a from the back side of the magnet 74.
　図６に示すように動作エリアＯＡはシリンダー３４ａの後ろ側に位置するとともに、シリンダー３４ａに対向する。一態様において、動作エリアＯＡの背後にアクチュエーター７３ａが位置していてもよい。動作エリアＯＡはアクチュエーター７３ａに向き合っていてもよい。把持部７２ａは動作エリアＯＡを跨いでもよい。このように配置することで動作エリアＯＡ内を運動する磁石７４とアクチュエーター７３ａとの干渉が避けられる。 As shown in FIG. 6, the operating area OA is located behind the cylinder 34a and faces the cylinder 34a. In one aspect, the actuator 73a may be located behind the operating area OA. The operating area OA may face the actuator 73a. The grip portion 72a may straddle the operating area OA. By arranging in this way, interference between the magnet 74 moving in the operating area OA and the actuator 73a can be avoided.
＜７．磁石の支え方と動かし方＞ <7. How to support and move the magnet>
　図７は撹拌機構７１ｃとシリンジ３５ａとを選んで正面から観察した状態を示す。本図において、流体デバイスは駆動装置に対してすでに装着されているものとする。図中においてカートリッジのケースは省略されている。 FIG. 7 shows a state in which the stirring mechanism 71c and the syringe 35a are selected and observed from the front. In this figure, it is assumed that the fluid device is already mounted on the drive unit. The cartridge case is omitted in the figure.
　図７において、アクチュエーター７３ｃはアーム７２ｃをシリンジ３５ａの長手方向に沿って往復運動させる。アーム７２ｃは磁石７４の往復運動方向に対する側方から磁石７４を保持する。言い換えればアーム７２ｃはシリンジ３５ａの側方から磁石７４を差し入れる。磁石７４はシリンジ３５ａの長手方向に沿って撹拌子７５をシリンジ３５ａ内で往復運動させる。ここで磁石７４は永久磁石又は電磁石でもよい。本実施例では磁石７４は永久磁石である。 In FIG. 7, the actuator 73c reciprocates the arm 72c along the longitudinal direction of the syringe 35a. The arm 72c holds the magnet 74 from the side with respect to the reciprocating direction of the magnet 74. In other words, the arm 72c inserts the magnet 74 from the side of the syringe 35a. The magnet 74 reciprocates the stirrer 75 in the syringe 35a along the longitudinal direction of the syringe 35a. Here, the magnet 74 may be a permanent magnet or an electromagnet. In this embodiment, the magnet 74 is a permanent magnet.
　図７において、シリンジ３５ａは吐出口３１aを下に、ピストン３２ａを上にして立っているものとする。シリンジ３５ａは直立していてもよい。磁石７４及び撹拌子７５の上方にホールド部７９ａが位置する。ホールド部７９ａの上方に把持部７２ａが位置する。 In FIG. 7, it is assumed that the syringe 35a stands with the discharge port 31a at the bottom and the piston 32a at the top. The syringe 35a may be upright. The hold portion 79a is located above the magnet 74 and the stirrer 75. The grip portion 72a is located above the hold portion 79a.
　図７において、磁石７４の往復運動中に磁石７４が撹拌子７５をシリンダー３４ａ内で落とすことがある。例としてはピストン３２ａに撹拌子７５がぶつかった時が挙げられる。このとき撹拌機構７１ｃはシリンダー３４ａの下端まで磁石７４を向かわせることが好ましい。あるいは磁石７４の往復運動はシリンダー３４ａの下端で折り返すものであることが好ましい。これにより、磁石７４は、磁石７４が落としてしまった撹拌子７５を再び拾い取ることができる。したがって血液の撹拌が継続する。 In FIG. 7, the magnet 74 may drop the stirrer 75 in the cylinder 34a during the reciprocating motion of the magnet 74. An example is when the stirrer 75 collides with the piston 32a. At this time, it is preferable that the stirring mechanism 71c directs the magnet 74 to the lower end of the cylinder 34a. Alternatively, the reciprocating motion of the magnet 74 is preferably one that folds back at the lower end of the cylinder 34a. As a result, the magnet 74 can pick up the stirrer 75 that the magnet 74 has dropped again. Therefore, blood agitation continues.
＜８．微細回路の構造及び機能＞ <8. Structure and function of fine circuit>
　図１に戻る。駆動装置７０は流体デバイス３０を駆動する。流体デバイス３０の役割は微細回路２０に希釈血ＤＢと押圧液ＰＬとを送ることで水力学的分級を行うことである。以下に微細回路２０の水力学的な説明を行う。本実施例において微細回路２０は血球を初めとする浮遊細胞の分離用の流路チップである。微細回路２０の構成は下記実施例に限定されない。 Return to Fig. 1. The drive device 70 drives the fluid device 30. The role of the fluid device 30 is to perform hydraulic classification by sending the diluted blood DB and the pressing liquid PL to the microcircuit 20. The hydraulic description of the microcircuit 20 will be described below. In this embodiment, the microcircuit 20 is a flow path chip for separating floating cells such as blood cells. The configuration of the microcircuit 20 is not limited to the following embodiment.
　図８は平面視した微細回路２０を示している。微細回路２０は主流路２３を有する。主流路２３の一方の端は入口２１ａとなっている。主流路２３のもう一方の端は出口２２ｃとなっている。微細回路２０はさらに副流路２４を有する。副流路２４の端は入口２１ｂとなっている。副流路２４の端は合流部２８にて主流路２３に接続している。 FIG. 8 shows a microcircuit 20 in a plan view. The microcircuit 20 has a main flow path 23. One end of the main flow path 23 is an inlet 21a. The other end of the main flow path 23 is an outlet 22c. The microcircuit 20 further has a subchannel 24. The end of the auxiliary flow path 24 is the inlet 21b. The end of the sub-flow path 24 is connected to the main flow path 23 at the merging portion 28.
　図８に示すように主流路２３は入口２１ａから出口２２ｃに向かって順に流路パート２５ａ～ｄを有する。流路パート２５ａ～ｄは入口２１ａから出口２２ｃまで一つながりとなっている。流路パート２５ａと流路パート２５ｂとの間に合流部２８がある。流路パート２５ｃで接続する枝流路２６ａ及び２６ｂの一端にさらに出口２２ａ及び出口２２ｂがある。 As shown in FIG. 8, the main flow path 23 has flow path parts 25a to 25d in order from the inlet 21a to the outlet 22c. The flow path parts 25a to d are connected from the inlet 21a to the outlet 22c. There is a confluence 28 between the flow path part 25a and the flow path part 25b. There are further outlets 22a and 22b at one end of the branch flow paths 26a and 26b connected by the flow path part 25c.
　図８に示す入口２１ａは希釈血ＤＢを入れたシリンジ３５ａと接続される。シリンジ３５ａからは、所定の流量で希釈血ＤＢを入口２１ａに送る。希釈血ＤＢは入口２１ａを経由して流路パート２５aに入る。 The inlet 21a shown in FIG. 8 is connected to the syringe 35a containing the diluted blood DB. From the syringe 35a, the diluted blood DB is sent to the inlet 21a at a predetermined flow rate. The diluted blood DB enters the flow path part 25a via the inlet 21a.
　図８に示す希釈血ＤＢは微細回路２０に導入される前に希釈しておくことが好ましい。希釈率は２～５００倍とすることが出来る。本実施例では希釈率を５０倍としてもよい。希釈はリン酸緩衝生理食塩水で行う。希釈血ＤＢの単位時間当たりの流量を１～１０００μｌ／分とすることが出来る。例えば５，１０，１５，２０，２５，３０，３５，４０，４５，５０，５５，６０，６５，７０，７５，８０，８５，９０，９５及び１００μｌ／分のいずれかとしてもよい。処理する時間を１分～３００分としてもよい。例えば５，１０，２０，３０，４０，５０，６０，９０，１２０，１５０，１８０，２１０，２４０及び２７０分のいずれかとしてもよい。一回の分級で例えば１５ｍｌの全血を希釈して得た液を微細回路２０で処理してもよい。 The diluted blood DB shown in FIG. 8 is preferably diluted before being introduced into the microcircuit 20. The dilution rate can be 2 to 500 times. In this example, the dilution rate may be 50 times. Dilution is done with phosphate buffered saline. The flow rate of the diluted blood DB per unit time can be 1 to 1000 μl / min. For example, it may be any of 5,10,15,20,25,30,35,40,45,50,55,60,65,70,75,80,85,90,95 and 100 μl / min. The processing time may be 1 minute to 300 minutes. For example, it may be any of 5, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 210, 240 and 270 minutes. The liquid obtained by diluting, for example, 15 ml of whole blood in one classification may be processed by the fine circuit 20.
　図８に示す微細回路２０は副流路２４を有する。副流路２４はシリンジ３５ｂと接続されている。シリンジ３５ｂには押圧液ＰＬが蓄えられている。押圧液ＰＬは浮遊細胞を含まない液体である。押圧液ＰＬは血球やその他の細胞にダメージを与えにくい液体である。押圧液ＰＬは緩衝液を含んでいてもよい。緩衝液はＰＢＳでもよい。シリンジ３５ｂ内に圧力をかけることで押圧液ＰＬは入口２１ｂから副流路２４に入る。押圧液ＰＬは副流路２４を流れる。押圧液ＰＬは流路パート２５ｂに流入する。 The microcircuit 20 shown in FIG. 8 has a subchannel 24. The subchannel 24 is connected to the syringe 35b. The pressing liquid PL is stored in the syringe 35b. Pressing liquid PL is a liquid that does not contain floating cells. Pressing liquid PL is a liquid that does not easily damage blood cells and other cells. The pressing liquid PL may contain a buffer liquid. The buffer may be PBS. By applying pressure into the syringe 35b, the pressing liquid PL enters the subchannel 24 from the inlet 21b. The pressing liquid PL flows through the auxiliary flow path 24. The pressing liquid PL flows into the flow path part 25b.
　図８に示す枝流路２６ａ及び２６ｂはいずれも主流路２３から分岐する流路である。流路パート２５ｃにおいて、上流側から順に枝流路２６ａ及び枝流路２６ｂがこの順で主流路２３から分岐する。主流路２３を間に挟んで副流路２４と対向する側に枝流路２６ａ及び２６ｂが配置されている。 Both the branch flow paths 26a and 26b shown in FIG. 8 are flow paths that branch from the main flow path 23. In the flow path part 25c, the branch flow path 26a and the branch flow path 26b branch from the main flow path 23 in this order from the upstream side. The branch flow paths 26a and 26b are arranged on the side facing the sub flow path 24 with the main flow path 23 in between.
　図８に示す枝流路２６ａ及び２６ｂはいずれも主流路２３から分岐する細流路を複数個有する。各細流路は主流路２３の上流から下流に向かって並ぶ。枝流路２６ａ及び２６ｂはそれぞれ出口２２ａ及び出口２２ｂに達する。枝流路２６ａ及び２６ｂ中の各細流路はそれぞれ出口２２ａ及び２２ｂの手前で合流する。流路パート２５ｄは出口２２ｃに達する。 Each of the branch flow paths 26a and 26b shown in FIG. 8 has a plurality of small flow paths branching from the main flow path 23. The small flow paths are lined up from the upstream to the downstream of the main flow path 23. The branch flow paths 26a and 26b reach the outlets 22a and 22b, respectively. The fine flow paths in the branch flow paths 26a and 26b merge before the outlets 22a and 22b, respectively. The flow path part 25d reaches the outlet 22c.
　図９は特に流路パート２５ｃ付近を拡大視した微細回路２０が示している。図は微細回路２０による浮遊細胞の分別の過程を模式的に表している。説明を簡単にするため、枝流路２６ａには１０本の細流路が、枝流路２６ｂには３本の細流路が代表して示されている。なお図９及び図１０は特許文献２より引用し、本実施例の説明に適するように一部を変更した。分級のメカニズムは特許文献２において特に詳細に説明されている。 FIG. 9 shows a microcircuit 20 in which the vicinity of the flow path part 25c is magnified. The figure schematically shows the process of separating floating cells by the microcircuit 20. For the sake of simplicity, the branch flow path 26a is represented by 10 small channels, and the branch flow path 26b is represented by 3 small channels. Note that FIGS. 9 and 10 are taken from Patent Document 2 and partially modified so as to be suitable for the description of this embodiment. The classification mechanism is described in particular detail in Patent Document 2.
　図９に示すように、流路パート２５ｂのさらに上流から希釈血ＤＢが連続的に流れてくる。希釈血ＤＢは細胞を大量に含んでいる。希釈血ＤＢの流れに対して、その側方より押圧液ＰＬの流れを連続的に接触させる。押圧液ＰＬは、希釈血ＤＢと同じ方向に流れながら、希釈血ＤＢの流れを押圧液ＰＬとは反対側に連続的に押し込む。結果として押圧液ＰＬは主流路２３を流れる細胞を、主流路２３の側方から連続的に押し込む。流路パート２５ｂにおいて、枝流路２６ａ及び枝流路２６ｂ側に連続的に浮遊細胞が押しやられるとともに、流路パート２５ｃにおいて、これらの枝流路に浮遊細胞が連続的に流れ込む。 As shown in FIG. 9, the diluted blood DB continuously flows from the upstream of the flow path part 25b. Diluted blood DB contains a large amount of cells. The flow of the pressing liquid PL is continuously contacted with the flow of the diluted blood DB from the side thereof. The pressing liquid PL continuously pushes the flow of the diluted blood DB to the opposite side of the pressing liquid PL while flowing in the same direction as the diluted blood DB. As a result, the pressing liquid PL continuously pushes the cells flowing through the main flow path 23 from the side of the main flow path 23. In the flow path part 25b, the floating cells are continuously pushed toward the branch flow path 26a and the branch flow path 26b, and in the flow path part 25c, the floating cells continuously flow into these branch flow paths.
　図９に示すように、枝流路２６ａには無核赤血球２７が連続的に流れ込む。流路パート２５ｃにおいて希釈血ＤＢ中の無核赤血球２７を水力学的に分級する。分級は希釈血ＤＢの流れのうち、押圧液ＰＬの流れとは接触していない側で連続的に行われる。 As shown in FIG. 9, annuclear erythrocytes 27 continuously flow into the branch flow path 26a. The anucleated erythrocytes 27 in the diluted blood DB are hydraulically classified in the channel part 25c. The classification is continuously performed on the side of the flow of the diluted blood DB that is not in contact with the flow of the pressing liquid PL.
　図９に示すように、枝流路２６ａは無核赤血球２７の除去流路として働く。枝流路２６ａの有する細流路の内接径は１１～１９μｍである。内接径は１２、１３、１４、１５、１６、１７、及び１８μｍのいずれかでもよい。 As shown in FIG. 9, the branch flow path 26a acts as a removal flow path for the anucleated erythrocytes 27. The inscribed diameter of the fine flow path of the branch flow path 26a is 11 to 19 μm. The inscribed diameter may be any of 12, 13, 14, 15, 16, 17, and 18 μm.
　図９に示すように枝流路２６ｂには有核細胞２９ａ－ｃが連続的に流れ込む。流路パート２５ｂの下流の流路パート２５ｃにおいて、希釈血ＤＢ中の有核細胞２９ａ－ｃを水力学的に分級する。分級は希釈血ＤＢの流れのうち、押圧液ＰＬの流れとは接触していない側で連続的に行われる。枝流路２６ｂより細胞懸濁液ＣＳを連続的に得る。 As shown in FIG. 9, nucleated cells 29a-c continuously flow into the branch flow path 26b. In the channel part 25c downstream of the channel part 25b, the nucleated cells 29a-c in the diluted blood DB are hydraulically classified. The classification is continuously performed on the side of the flow of the diluted blood DB that is not in contact with the flow of the pressing liquid PL. Cell suspension CS is continuously obtained from the branch flow path 26b.
　図９に示すように枝流路２６ｂは有核細胞２９ａ－ｃの回収流路として働く。枝流路２６ｂの有する細流路の内接径は枝流路２６ａの有する細流路の内接径よりも小さい。枝流路２６ｂの有する細流路の内接径は１７～３０μｍである。内接径は１８、１９、２０、２１、２２、２３、２４、２５、２６、２７、２８及び２９μｍのいずれかでもよい。有核赤血球を初めとする有核細胞の径の大きさは１１～１３μｍと考えられる。 As shown in FIG. 9, the branch flow path 26b functions as a recovery flow path for the nucleated cells 29a-c. The inscribed diameter of the fine channel of the branch flow path 26b is smaller than the inscribed diameter of the fine channel of the branch flow path 26a. The inscribed diameter of the fine flow path of the branch flow path 26b is 17 to 30 μm. The inscribed diameter may be any of 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28 and 29 μm. The diameter of nucleated cells including nucleated red blood cells is considered to be 11 to 13 μm.
　図９に示す枝流路２６ａ及び２６ｂの各細流路の内接径は細流路の直交断面における内接円の直径である。本実施例において各細流路の断面は四角である。細流路の断面は他の多角形でも円でもよい。他の枝流路において同様である。 The inscribed diameter of each of the branch flow paths 26a and 26b shown in FIG. 9 is the diameter of the inscribed circle in the orthogonal cross section of the fine flow path. In this embodiment, the cross section of each microchannel is square. The cross section of the microchannel may be another polygon or a circle. The same is true for other branch channels.
　図９に示す枝流路２６ａ及び２６ｂに取り込まれなかった浮遊細胞や血漿はフロースルーＦＴとして連続的に流路パート２５ｄを通過する。その後、図８に示す出口２２ｃに到達する。例えば凝集した血球などがフロースルーＦＴに含まれる。 Floating cells and plasma not taken up in the branch flow paths 26a and 26b shown in FIG. 9 continuously pass through the flow path part 25d as a flow-through FT. After that, it reaches the exit 22c shown in FIG. For example, aggregated blood cells are included in the flow-through FT.
＜９．水力学的な分級＞ <9. Hydraulic classification>
　図１０には流路パート２５ｃに焦点を絞りつつ微細回路の詳細が示されている。本実施例に係る水力学的な分級では、細流路の内接径の値が分級される浮遊細胞の径の最大値と等しくなっているわけではない。したがって本実施例に係る水力学的な分級は単純な濾過と異なる。本実施例に係る水力学的な分級を以下に説明する。 FIG. 10 shows the details of the microcircuit while focusing on the flow path part 25c. In the hydraulic classification according to this embodiment, the value of the inscribed diameter of the microchannel is not equal to the maximum value of the diameter of the suspended cells to be classified. Therefore, the hydraulic classification according to this embodiment is different from simple filtration. The hydraulic classification according to this embodiment will be described below.
　図１０には流路パート２５ｃが示されている。さらに枝流路２６ａが表されている。説明を簡単にするため枝流路２６ａを構成する細流路を一本のみとする。図１０の説明において枝流路２６ａを構成する細流路を単に枝流路２６ａと称する。 FIG. 10 shows the flow path part 25c. Further, a branch flow path 26a is represented. For the sake of simplicity, only one fine flow path constitutes the branch flow path 26a. In the description of FIG. 10, the fine flow path constituting the branch flow path 26a is simply referred to as a branch flow path 26a.
　図１０に示すように流路パート２５ｃには液流ＬＦが連続的に導入される。液流ＬＦは上述の希釈血ＤＢと押圧液ＰＬとを含む。液流ＬＦ中でこれらの液は部分的に混じり合っている。液流ＬＦ中には大きな細胞として有核細胞２９ａと、小さな細胞として無核赤血球２７とが懸濁している。図中において有核細胞２９ａは他の有核細胞を代表して描かれている。 As shown in FIG. 10, the liquid flow LF is continuously introduced into the flow path part 25c. The liquid flow LF contains the above-mentioned diluted blood DB and the pressing liquid PL. These liquids are partially mixed in the liquid flow LF. Nucleated cells 29a as large cells and annuclear erythrocytes 27 as small cells are suspended in the fluid flow LF. In the figure, the nucleated cell 29a is drawn on behalf of other nucleated cells.
　図１０において液流ＬＦのうち、枝流路２６ａへ導入される部分を液流ＬＥとする。液流ＬＦのうち、枝流路２６ａへ導入されず、下流に向かって流れていく部分を液流ＬＧとする。液流ＬＥの流量がある値より小さいものとする。ここで流量は液流ＬＥの断面に比例する。液流ＬＥは枝流路２６ａ側の流路パート２５ｃの内壁に位置する。液流ＬＥの流量は枝流路２６ａ中の液流ＬＥの流速にも比例する。 In FIG. 10, the portion of the liquid flow LF introduced into the branch flow path 26a is referred to as the liquid flow LE. The portion of the liquid flow LF that is not introduced into the branch flow path 26a and flows downstream is referred to as the liquid flow LG. It is assumed that the flow rate of the liquid flow LE is smaller than a certain value. Here, the flow rate is proportional to the cross section of the liquid flow LE. The liquid flow LE is located on the inner wall of the flow path part 25c on the branch flow path 26a side. The flow rate of the liquid flow LE is also proportional to the flow rate of the liquid flow LE in the branch flow path 26a.
　図１０において液流ＬＥ中を流れる無核赤血球２７が枝流路２６ａへ導入される。一方、有核細胞２９ａはその体積の半分以上が液流ＬＧ側に属している。有核細胞２９ａは液流ＬＥに対して一部接触するに過ぎない。このため有核細胞２９ａは枝流路２６ａへは導入されない。このとき有核細胞２９ａの径は枝流路２６ａの内接径より小さくてもよい。仮に液流ＬＥの流量が大きくなれば液流ＬＥの断面が大きくなる。この場合、有核細胞２９ａが液流ＬＥに飲み込まれることで、枝流路２６ａへ誘導されることも考えられる。 In FIG. 10, annuclear erythrocytes 27 flowing in the liquid flow LE are introduced into the branch flow path 26a. On the other hand, more than half of the volume of the nucleated cell 29a belongs to the liquid flow LG side. Nucleated cells 29a make only partial contact with the fluid LE. Therefore, the nucleated cells 29a are not introduced into the branch flow path 26a. At this time, the diameter of the nucleated cell 29a may be smaller than the inscribed diameter of the branch flow path 26a. If the flow rate of the liquid flow LE becomes large, the cross section of the liquid flow LE becomes large. In this case, it is conceivable that the nucleated cells 29a are swallowed by the liquid flow LE and are guided to the branch flow path 26a.
　図１０において有核細胞２９ａは液流ＬＧに乗ってさらに下流に運ばれる。以上により、枝流路２６ａからはある大きさ以上の浮遊細胞を含まない流体を回収することができる。また有核細胞２９ａ及びその他の有核細胞は下流で分級を受ける。 In FIG. 10, the nucleated cells 29a are carried further downstream on the liquid flow LG. As described above, a fluid having a certain size or larger and containing no suspended cells can be recovered from the branch flow path 26a. Nucleated cells 29a and other nucleated cells are also classified downstream.
＜１０．分級作業＞ <10. Classification work ＞
　以下において、駆動装置と流体デバイスを用いた分級作業を示す。図１１は血液内の細胞を分級する作業のための微細回路（Ｆ）の動作の流れ図を示している。さらに微細回路（Ｆ）を作動させるための往復機構（Ａ）、押圧機構（Ｂ）及び撹拌機構（Ｍ）の動作の流れ図が示されている。 Below, the classification work using the drive device and the fluid device is shown. FIG. 11 shows a flow chart of the operation of the microcircuit (F) for the work of classifying cells in blood. Further, a flow chart of the operation of the reciprocating mechanism (A), the pressing mechanism (B) and the stirring mechanism (M) for operating the fine circuit (F) is shown.
　図１１に示すステップＳ９０の開始からステップＳ９９の終了までの各ステップを、図２～図４やさらに図１２を参照しながら説明する。図１２は血液の取り込みの前の駆動装置７０及び流体デバイス３０の状態を表す。 Each step from the start of step S90 shown in FIG. 11 to the end of step S99 will be described with reference to FIGS. 2 to 4 and further FIG. FIG. 12 shows the state of the drive device 70 and the fluid device 30 prior to blood uptake.
　図１１のステップＳ９０の開始にあたり、事前の準備として図１２に示すように採血管５１に血液ＢＬを採取する。本実施例では血液ＢＬは全血である。血液ＢＬを蓄えた採血管５１を取入口５０に取り付ける。さらにシリンジ３５ａ内に予め希釈液ＤＬを注液しておくことで、これをシリンジ３５ａ内に配置する。さらにシリンジ３５ａ内に撹拌子７５も配置する。さらにシリンジ３５ｂ内に予め押圧液ＰＬを注液することで、これをシリンジ３５ｂ内に配置する。事前の準備が終わり次第、分級作業を開始する。 At the start of step S90 in FIG. 11, blood BL is collected in the blood collection tube 51 as shown in FIG. 12 as a preliminary preparation. In this example, the blood BL is whole blood. The blood collection tube 51 storing the blood BL is attached to the inlet 50. Further, by injecting the diluted solution DL into the syringe 35a in advance, this is placed in the syringe 35a. Further, a stirrer 75 is also arranged in the syringe 35a. Further, by injecting the pressing liquid PL into the syringe 35b in advance, this is placed in the syringe 35b. As soon as the preparations are completed, the classification work will start.
　図１１のステップＳ９１にて微細回路（Ｆ）及び周辺の導管の内部を液体で浸漬する。図１２に示すように往復機構７１ａがシリンジ３５ａを押圧することで、シリンジ３５ａが希釈液ＤＬを第２導管１１ｂ、分岐１５、及び第３導管１１ｃ並びに微細回路２０内に供給する。この時、取入バルブ７６ａを閉じるとともに開始バルブ７６ｂを開いておく。 In step S91 of FIG. 11, the inside of the microcircuit (F) and the surrounding conduit is immersed in a liquid. As shown in FIG. 12, when the reciprocating mechanism 71a presses the syringe 35a, the syringe 35a supplies the diluent DL into the second conduit 11b, the branch 15, the third conduit 11c, and the microcircuit 20. At this time, the intake valve 76a is closed and the start valve 76b is opened.
　図１２に示すように押圧機構７１ｂがシリンジ３５ｂを押圧することで、シリンジ３５ｂが押圧液ＰＬを第４導管１２及び微細回路２０内に供給する。供給された各液体が各導管及び微細回路２０の内部から空気を追い出す。したがって、これらの液体で内部が浸漬される。図１１に示すステップＳ９１において撹拌機構（Ｍ）は休止している。 As shown in FIG. 12, when the pressing mechanism 71b presses the syringe 35b, the syringe 35b supplies the pressing liquid PL into the fourth conduit 12 and the microcircuit 20. Each supplied liquid expels air from the interior of each conduit and microcircuit 20. Therefore, the inside is immersed in these liquids. In step S91 shown in FIG. 11, the stirring mechanism (M) is stopped.
　次に図１１のステップＳ９２にて微細回路（Ｆ）の浸漬を休止する。往復機構７１ａ及び押圧機構７１ｂによる押圧を休止することで、微細回路（Ｆ）への送液が止まる。微細回路（Ｆ）も休止する。このステップＳ９２において撹拌機構（Ｍ）も休止してもよい。 Next, in step S92 of FIG. 11, the immersion of the fine circuit (F) is stopped. By suspending the pressing by the reciprocating mechanism 71a and the pressing mechanism 71b, the liquid feeding to the fine circuit (F) is stopped. The fine circuit (F) also pauses. The stirring mechanism (M) may also be paused in step S92.
　次に図１１のステップＳ９３にて往復機構（Ａ）がピストンを引く。まず図２に示すように取入バルブ７６ａを開くとともに開始バルブ７６ｂを閉じておく。バルブの操作により採血管５１から取入口５０及び分岐１５を経由してシリンジ３５ａに至るルートが形成される。ピストン３２ａを引くことでこのルートに沿って血液ＢＬをシリンジ３５ａ内に取り込む。すなわちシリンジ３５ａの容積拡大に伴い取入口５０から分岐１５を経由してシリンジ３５ａ内に所定量の血液ＢＬを取り込む。 Next, in step S93 of FIG. 11, the reciprocating mechanism (A) pulls the piston. First, as shown in FIG. 2, the intake valve 76a is opened and the start valve 76b is closed. By operating the valve, a route from the blood collection tube 51 to the syringe 35a via the intake 50 and the branch 15 is formed. By pulling the piston 32a, the blood BL is taken into the syringe 35a along this route. That is, as the volume of the syringe 35a is expanded, a predetermined amount of blood BL is taken into the syringe 35a from the intake port 50 via the branch 15.
　図２に示すように血液ＢＬがシリンジ３５ａ内に取り込まれる際、希釈液ＤＬによって血液ＢＬがシリンジ３５ａ内で希釈される。血液中の浮遊細胞がシリンジ３５ａ内で沈殿しないように、撹拌機構（Ｍ）は、撹拌子７５をシリンジ３５ａの外側から動かして希釈液ＤＬ及び血液を撹拌する。また撹拌子７５による撹拌により、希釈前の血液ＢＬと希釈液ＤＬとの混合を十分なものとしてもよい。図１１に示すステップＳ９３において微細回路（Ｆ）及び押圧機構（Ｂ）は休止している。 As shown in FIG. 2, when the blood BL is taken into the syringe 35a, the blood BL is diluted in the syringe 35a by the diluent DL. The stirring mechanism (M) moves the stirrer 75 from the outside of the syringe 35a to stir the diluent DL and the blood so that the suspended cells in the blood do not settle in the syringe 35a. Further, the mixing of the blood BL before dilution and the diluted solution DL may be sufficient by stirring with the stirrer 75. In step S93 shown in FIG. 11, the microcircuit (F) and the pressing mechanism (B) are stopped.
　図１１に示すステップＳ９４において往復機構（Ａ）による血液の引き込みを休止する。図３に示すように微細回路（Ｆ）に当たる微細回路２０及び押圧機構（Ｂ）に当たる押圧機構７１ｂは休止している。他の例において押圧機構７１ｂは休止せず押圧を継続してもよい。撹拌機構（Ｍ）は希釈血ＤＢの撹拌を継続する。 In step S94 shown in FIG. 11, the drawing of blood by the reciprocating mechanism (A) is stopped. As shown in FIG. 3, the fine circuit 20 corresponding to the fine circuit (F) and the pressing mechanism 71b corresponding to the pressing mechanism (B) are stationary. In another example, the pressing mechanism 71b may continue pressing without pausing. The stirring mechanism (M) continues stirring the diluted blood DB.
　図１１に示すステップＳ９５において微細回路（Ｆ）で血液中の血球を分級する。図４に示すように開始バルブ７６ｂを開け放つ。さらに取入バルブ７６ａを閉じて圧力を全て微細回路２０に仕向ける。これによりシリンジ３５ａから分岐１５を経由して微細回路２０に至るルートが形成される。 In step S95 shown in FIG. 11, blood cells in blood are classified by a microcircuit (F). The start valve 76b is opened and released as shown in FIG. Further, the intake valve 76a is closed and all the pressure is directed to the fine circuit 20. As a result, a route from the syringe 35a to the microcircuit 20 via the branch 15 is formed.
　図１１に示すステップＳ９５において往復機構（Ａ）及び押圧機構（Ｂ）が各シリンジに対して押圧する。図４において、往復機構７１ａがピストン３２ａを押す。ピストン３２ａを押すのは、各バルブによってルートが形成されるのと同時でもよい。シリンジ３５ａはピストン３２ａの生じる圧力によって微細回路２０内に向かって希釈血ＤＢを連続的に流し入れる。 In step S95 shown in FIG. 11, the reciprocating mechanism (A) and the pressing mechanism (B) press against each syringe. In FIG. 4, the reciprocating mechanism 71a pushes the piston 32a. Pushing the piston 32a may be simultaneous with the formation of a route by each valve. The syringe 35a continuously flows the diluted blood DB into the microcircuit 20 by the pressure generated by the piston 32a.
　図４において、往復機構７１ａがピストン３２ａを押す間、さらに押圧機構７１ｂがピストン３２ｂを押す。シリンジ３５ｂはピストン３２ｂの生じる圧力によって微細回路２０内に向かって押圧液ＰＬを連続的に流し入れる。微細回路２０は押圧液ＰＬを用いながら希釈血ＤＢ中の浮遊細胞を連続的に分級する。 In FIG. 4, while the reciprocating mechanism 71a pushes the piston 32a, the pressing mechanism 71b further pushes the piston 32b. The syringe 35b continuously flows the pressing liquid PL into the microcircuit 20 by the pressure generated by the piston 32b. The microcircuit 20 continuously classifies suspended cells in the diluted blood DB while using the pressing solution PL.
　図４において微細回路２０内で、血球又は血球ではない浮遊細胞を水力学的に分級する。水力学的分級の詳細は図８～１０を用いて説明した。一態様において微細回路２０ではPBMC（末梢血単核細胞）の分離及び濃縮ができる。さらに微細回路２０の下面の排出口から分級された細胞を取り出してもよい。 In FIG. 4, blood cells or floating cells that are not blood cells are hydraulically classified in the microcircuit 20. Details of the hydraulic classification have been described with reference to FIGS. 8-10. In one embodiment, the microcircuit 20 can separate and concentrate PBMC (peripheral blood mononuclear cells). Further, the classified cells may be taken out from the discharge port on the lower surface of the microcircuit 20.
　図１１に示すステップＳ９５において所定量の希釈血ＤＢを処理し終えた後に、ステップＳ９６で往復機構（Ａ）及び押圧機構（Ｂ）による押圧を休止する。微細回路（Ｆ）における分級も休止する。またこれらに合わせて撹拌機構（Ｍ）による希釈血の撹拌を休止してもよい。以上により全ての処理を終え、ステップＳ９９で分級作業は終了する。必要に応じて分級作業を再開してもよい。 After processing a predetermined amount of diluted blood DB in step S95 shown in FIG. 11, the pressing by the reciprocating mechanism (A) and the pressing mechanism (B) is stopped in step S96. Classification in the fine circuit (F) is also suspended. Further, the stirring of the diluted blood by the stirring mechanism (M) may be stopped in accordance with these. As described above, all the processes are completed, and the classification work is completed in step S99. The classification work may be resumed if necessary.
＜１１．制御ユニットの構成＞ <11. Control unit configuration>
　以下において、駆動装置を制御するための電子的な構成の一例を説明する。駆動装置の制御の態様は下記実施例に限定されない。 Below, an example of an electronic configuration for controlling a drive device will be described. The mode of control of the drive device is not limited to the following examples.
　図１３は制御ユニット８０を模式的に表す。制御ユニット８０はシーケンサー８１を備える。シーケンサー８１はＰＬＣ（プログラマブル・ロジック・コントローラー）である。シーケンサー８１は不揮発性のメモリー８２を備える。メモリー８２は図１１に示した各機構の協調動作のプログラムを記憶する。シーケンサー８１はメモリー８２に記憶されたプログラムから導き出されるタイムスケジュールに沿って、協調動作を自動実行する。 FIG. 13 schematically shows the control unit 80. The control unit 80 includes a sequencer 81. The sequencer 81 is a PLC (programmable logic controller). The sequencer 81 includes a non-volatile memory 82. The memory 82 stores the program of the cooperative operation of each mechanism shown in FIG. The sequencer 81 automatically executes the cooperative operation according to the time schedule derived from the program stored in the memory 82.
　図１３に示すように制御ユニット８０はさらにモータードライバー８３ａ，８３ｂ及び８３ｃを備える。モータードライバー８３ａ，８３ｂ及び８３ｃはそれぞれシーケンサー８１と接続する。モータードライバー８３ａ，８３ｂ及び８３ｃは、それぞれアクチュエーター７３ａ，７３ｂ及び７３ｃに接続する。アクチュエーター７３ａ，７３ｂ及び７３ｃはそれぞれ往復機構（Ａ）、押圧機構（Ｂ）及び撹拌機構（Ｍ）の構成要素である。モータードライバー８３ａ，８３ｂ及び８３ｃは、それぞれ往復機構（Ａ）、押圧機構（Ｂ）及び撹拌機構（Ｍ）を作動する。 As shown in FIG. 13, the control unit 80 further includes motor drivers 83a, 83b and 83c. The motor drivers 83a, 83b and 83c are connected to the sequencer 81, respectively. The motor drivers 83a, 83b and 83c are connected to the actuators 73a, 73b and 73c, respectively. The actuators 73a, 73b and 73c are components of the reciprocating mechanism (A), the pressing mechanism (B) and the stirring mechanism (M), respectively. The motor drivers 83a, 83b and 83c operate the reciprocating mechanism (A), the pressing mechanism (B) and the stirring mechanism (M), respectively.
　図１３に示すように制御ユニット８０はさらに取入バルブ７６ａ及び開始バルブ７６ｂに接続する。取入バルブ７６ａ及び開始バルブ７６ｂはいずれもソレノイドで作動するピンチバルブでもよい。制御ユニット８０は往復機構（Ａ）の作動に合わせて取入バルブ７６ａ及び開始バルブ７６ｂを作動する。 As shown in FIG. 13, the control unit 80 is further connected to the intake valve 76a and the start valve 76b. Both the intake valve 76a and the start valve 76b may be a pinch valve operated by a solenoid. The control unit 80 operates the intake valve 76a and the start valve 76b in accordance with the operation of the reciprocating mechanism (A).
　図１３に示すように駆動装置７０はさらに電源８５を備える。電源８５はシーケンサー８１並びにモータードライバー８３ａ，８３ｂ及び８３ｃにそれぞれ接続する。電源８５は制御ユニット８０に供給する。制御ユニット８０は電源８５の電力で作動する。 As shown in FIG. 13, the drive device 70 further includes a power supply 85. The power supply 85 is connected to the sequencer 81 and the motor drivers 83a, 83b and 83c, respectively. The power supply 85 supplies to the control unit 80. The control unit 80 operates with the electric power of the power source 85.
　図１３に示すように電源８５はモータードライバー８３ａ，８３ｂ及び８３ｃをそれぞれ経由してアクチュエーター７３ａ，７３ｂ及び７３ｃに電力を供給する。各モータードライバーとアクチュエーターは電源８５の電力で作動する。 As shown in FIG. 13, the power supply 85 supplies electric power to the actuators 73a, 73b and 73c via the motor drivers 83a, 83b and 83c, respectively. Each motor driver and actuator is powered by power 85.
　図１３に図示していないが電源８５は取入バルブ７６ａ及び開始バルブ７６ｂに接続してもよい。電源８５は取入バルブ７６ａ及び開始バルブ７６ｂの作動に必要な電力供給してもよい。制御ユニット８０の機能は全て駆動装置７０内で完結してもよい。一部の機能が駆動装置７０の外にあってもよい。 Although not shown in FIG. 13, the power supply 85 may be connected to the intake valve 76a and the start valve 76b. The power supply 85 may supply the power required to operate the intake valve 76a and the start valve 76b. All the functions of the control unit 80 may be completed in the drive device 70. Some functions may be outside the drive 70.
　なお、本発明は上記実施形態や実施例に限られたものではなく、趣旨を逸脱しない範囲で適宜変更することが可能である。 The present invention is not limited to the above embodiments and examples, and can be appropriately modified without departing from the spirit.
　図１４は駆動装置の変形例を示す正面図である。駆動装置４０は、微細回路２０と、リザーバー４５と、シリンジ３５ａと、シリンジ３５ｂとを協働させる。リザーバー４５は分級前の血液を蓄える。これらの要素は、図１等に示す流体デバイス３０としてやそのカートリッジとして統合されてはいない。 FIG. 14 is a front view showing a modified example of the drive device. The drive device 40 makes the microcircuit 20, the reservoir 45, the syringe 35a, and the syringe 35b cooperate with each other. The reservoir 45 stores preclassified blood. These elements are not integrated as the fluid device 30 shown in FIG. 1 or the like or as a cartridge thereof.
　図１４に示す駆動装置４０は図１等に示す三方の分岐１５や、分岐１５に繋がる血液の取入口５０を用いない。また図１等に示す分岐１５における血液の進行方向を整理するために、バルブ７６ａやバルブ７６ｂの開閉を制御することはしない。駆動装置４０は、他の点で図１等に示す駆動装置７０と共通する。 The drive device 40 shown in FIG. 14 does not use the three-way branch 15 shown in FIG. 1 or the like or the blood intake 50 connected to the branch 15. Further, in order to arrange the traveling direction of blood in the branch 15 shown in FIG. 1 and the like, opening and closing of the valve 76a and the valve 76b is not controlled. The drive device 40 is otherwise common to the drive device 70 shown in FIG. 1 and the like.
　図１４に示すように駆動装置４０は制御ユニット４８を備える。制御ユニット４８は、往復機構７１ａと、装着機構４６と、押圧機構７１ｂと、撹拌機構７１ｃとを備える。駆動装置４０は、これらの協調動作を制御する制御ユニット４８を備える。制御ユニット４８は図１等に示すバルブ７６ａ及びバルブ７６ｂを制御せず、代わりに図１４に示す装着機構４６を制御する点で制御ユニット８０と異なる。制御ユニット４８は他の点で制御ユニット８０と共通する。 As shown in FIG. 14, the drive device 40 includes a control unit 48. The control unit 48 includes a reciprocating mechanism 71a, a mounting mechanism 46, a pressing mechanism 71b, and a stirring mechanism 71c. The drive device 40 includes a control unit 48 that controls these cooperative operations. The control unit 48 differs from the control unit 80 in that it does not control the valves 76a and 76b shown in FIG. 1 and the like, but instead controls the mounting mechanism 46 shown in FIG. The control unit 48 is otherwise common to the control unit 80.
　図１４の右上に示すように往復機構７１ａは、シリンジ３５ａの有するピストン３２ａを引くことで、シリンジ３５ａ内に向かって、リザーバー４５から血液を取り込む。一態様においてシリンジ３５ａは、吐出口３１ａを介して血液を取り込む。 As shown in the upper right of FIG. 14, the reciprocating mechanism 71a takes in blood from the reservoir 45 toward the inside of the syringe 35a by pulling the piston 32a of the syringe 35a. In one aspect, the syringe 35a takes in blood through the discharge port 31a.
　図１４に示すように、シリンジ３５ａ内にあらかじめ希釈液と撹拌子７５とを配置しておくことが好ましい。またシリンジ３５ｂ内にも押圧液ＰＬを配置しておくことが好ましい。 As shown in FIG. 14, it is preferable to arrange the diluent and the stirrer 75 in advance in the syringe 35a. It is also preferable to dispose the pressing liquid PL in the syringe 35b.
　図１４の右下に示すように装着機構４６は、シリンジ３５ａをリザーバー４５のある場所から、微細回路２０のある場所に運搬する。装着機構４６は、シリンジ３５ａの吐出口３１ａを微細回路２０の入口２１ａに装着する。 As shown in the lower right of FIG. 14, the mounting mechanism 46 transports the syringe 35a from the location of the reservoir 45 to the location of the microcircuit 20. The mounting mechanism 46 mounts the discharge port 31a of the syringe 35a at the inlet 21a of the microcircuit 20.
　図１４に示すように微細回路２０の入口２１ａにはアダプター４３ａが取り付けられている。装着機構４６は、アダプター４３ａに吐出口３１ａを挿入する。微細回路２０の入口２１ａとシリンジ３５ａの吐出口３１ａとはアダプター４３ａを介して結合する。アダプター４３ａは吐出口３１ａの入口２１ａに対する脱着を自在にするものでもよい。吐出口３１ａの装着後において、アダプター４３ａは吐出口３１ａを入口２１ａから取り外せなくしてもよい。 As shown in FIG. 14, an adapter 43a is attached to the inlet 21a of the microcircuit 20. The mounting mechanism 46 inserts the discharge port 31a into the adapter 43a. The inlet 21a of the microcircuit 20 and the discharge port 31a of the syringe 35a are coupled via an adapter 43a. The adapter 43a may be freely attached to and detached from the inlet 21a of the discharge port 31a. After mounting the discharge port 31a, the adapter 43a may not be able to remove the discharge port 31a from the inlet 21a.
　図１４に示すように微細回路２０の上面の入り口２１ｂにシリンジ３５ｂの吐出口３１ｂを接続する。微細回路２０の入口２１ｂにはアダプター４３ｂが取り付けられている。微細回路２０の入口２１ａとシリンジ３５ａの吐出口３１ａとはアダプター４３ａを介して結合する。 As shown in FIG. 14, the discharge port 31b of the syringe 35b is connected to the inlet 21b on the upper surface of the microcircuit 20. An adapter 43b is attached to the inlet 21b of the microcircuit 20. The inlet 21a of the microcircuit 20 and the discharge port 31a of the syringe 35a are coupled via an adapter 43a.
　図１４に示すように撹拌機構７１ｃでシリンジ３５ａ内に配置された撹拌子をシリンジ３５ａの外側から動かすことでシリンジ３５ａ内の血液と希釈液とを混合撹拌して希釈血ＤＢを得る。シリンジ３５ａ内に希釈血ＤＢが蓄えられている間に、磁石７４が撹拌子７５をシリンジ３５ａの外側から動かすことでシリンジ３５ａ内の血液を撹拌する。 As shown in FIG. 14, the stirrer arranged in the syringe 35a is moved by the stirring mechanism 71c from the outside of the syringe 35a to mix and stir the blood in the syringe 35a and the diluent to obtain the diluted blood DB. While the diluted blood DB is stored in the syringe 35a, the magnet 74 moves the stirrer 75 from the outside of the syringe 35a to stir the blood in the syringe 35a.
　図１４に示すように往復機構７１ａは、ピストン３２ａを押すことでシリンジ３５ａから吐出口３１ａ及び入口２１ａを経由して微細回路２０に向かって希釈血ＤＢを連続的に流し入れる。押圧機構７１ｂは、往復機構７１ａがピストン３２ａを押すのに合わせて、シリンジ３５ｂの有するピストンＢを押すことでシリンジ３５ｂから微細回路２０に向かって押圧液ＰＬを連続的に流し入れる。 As shown in FIG. 14, the reciprocating mechanism 71a continuously flows the diluted blood DB from the syringe 35a toward the microcircuit 20 via the discharge port 31a and the inlet 21a by pushing the piston 32a. The pressing mechanism 71b continuously flows the pressing liquid PL from the syringe 35b toward the microcircuit 20 by pushing the piston B of the syringe 35b in accordance with the reciprocating mechanism 71a pushing the piston 32a.
　以上により、図１４に示すリザーバー４５に蓄えられた血液内の細胞を微細回路２０で分級することができる。微細回路２０における分級の詳細は図８～１０に示す通りに行う。 From the above, the cells in the blood stored in the reservoir 45 shown in FIG. 14 can be classified by the microcircuit 20. Details of classification in the fine circuit 20 are performed as shown in FIGS. 8 to 10.
　この出願は、２０１９年３月２９日に出願された日本出願特願２０１９－０６６２１２及び２０２０年２月１０日に出願された日本出願特願２０２０－０２０６６５を基礎とする優先権を主張し、その開示の全てをここに取り込む。 This application claims priority based on Japanese application Japanese Patent Application No. 2019-066212 filed on March 29, 2019 and Japanese application Japanese Patent Application No. 2020-02665 filed on February 10, 2020. Incorporate all of the disclosure here.
１０　配管系，　１１ａ　第１導管，　１１ｂ　第２導管，　１１ｃ　第３導管，　１２　第４導管，　１５　分岐，　２０　微細回路，　２１ａ－ｂ　入口，　２２ａ－ｃ　出口，　２３　主流路，　２４　副流路，　２５ａ－ｄ　流路パート，　２６ａ－ｂ　枝流路，　２７　無核赤血球，　２８　合流部，　２９ａ－ｃ　有核細胞，　３０　流体デバイス，３１a－ｂ　吐出口,　３２ａ－ｂ　ピストン，　３４ａ－ｂ　シリンダー，　３５ａ－ｂ　シリンジ，　３６ａ－ｂ　フランジ，　３７ａ－ｂ　ロッド，　３８ａ－ｂ　フランジ，　４０　駆動装置，　４３ａ－ｂ　アダプター,　４５　リザーバー,　４６　装着機構,　４８，制御ユニット，　５０　取入口，　５１　採血管，　５５　ケース，　５６　採取容器，　５７　排液容器，　５９　アクセス窓，　７０　駆動装置，　７１ａ　往復機構，　７１ｂ　押圧機構，　７１ｃ　撹拌機構，　７２ａ－ｂ　把持部，　７２ｃ　アーム，　７３ａ－ｃ　アクチュエーター，　７４　磁石，　７５　撹拌子，　７６ａ　取入バルブ，　７６ｂ　開始バルブ，　７７ａ－ｂ　押さえ具，　７８ａ－ｂ　支持器，　７９ａ－ｂ　ホールド部，　８０　制御ユニット，　８１　シーケンサー，　８２　メモリー，　８３ａ－ｂ　モータードライバー，　８５　電源，　８６　取り付け面，　８７ａ－ｂ　ガイド，　ＢＬ　血液，　ＣＳ　細胞懸濁液，　ＤＢ　希釈血，　ＤＬ　希釈液，　ＦＴ　フロースルー，　ＬＥ　液流，　ＬＦ　液流，　ＬＧ　液流，　ＯＡ　動作エリア，　ＰＬ　押圧液，　Ｓ９０－９６　ステップ，　Ｓ９９　ステップ 10 Piston system, 11a 1st conduit, 11b 2nd conduit, 11c 3rd conduit, 12 4th conduit, 15 branch, 20 microcircuit, 21ab inlet, 22ac outlet, 23 main flow path, 24 sub-channel, 25ad flow path part, 26ab branch flow path, 27 non-nuclear red erythrocytes, 28 confluence, 29a-c nucleated cells, 30 fluid device, 31ab discharge port, 32ab piston, 34ab cylinder, 35ab syringe, 36ab flange, 37ab rod, 38ab flange, 40 drive device, 43ab adapter, 45 reservoir, 46 mounting mechanism, 48, control unit, 50 intake, 51 blood collection tube, 55 Case, 56 collection valve, 57 drainage container, 59 access window, 70 drive device, 71a reciprocating mechanism, 71b pressing mechanism, 71c stirring mechanism, 72ab grip, 72c arm, 73a-c actuator, 74 magnet, 75 stirring Child, 76a intake valve, 76b start valve, 77ab presser, 78ab support, 79ab hold, 80 control unit, 81 sequencer, 82 memory, 83ab motor driver, 85 power supply, 86 installation Surface, 87ab guide, BL blood, CS cell suspension, DB diluted blood, DL diluent, FT flow-through, LE fluid flow, LF fluid flow, LG fluid flow, OA operating area, PL pressing fluid, S90- 96 steps, S99 steps

Claims (13)

  1. 　流体デバイスを駆動するための駆動装置であって、
    　前記流体デバイスは、
    　　血液中の細胞を水力学的に分級するための微細回路と、
    　　血液の取入口と、
    　　血液を取り込むとともに蓄えるためのシリンジＡと、
    　　前記微細回路、前記取入口及び前記シリンジＡからなる三方の間を連絡する分岐と、
    　　押圧液を蓄えるためのシリンジＢであって前記微細回路に接続するものと、
    　を備え、
    　前記駆動装置は、
    　往復機構と、押圧機構と、撹拌機構と、これらの協調動作を制御する制御ユニットと、を備え
    　前記往復機構は、前記シリンジＡの有するピストンＡを引くことで、前記取入口から前記分岐を経由して前記シリンジＡ内に血液を取り込み、さらに前記ピストンＡを押すことで前記シリンジＡから前記分岐を経由して前記微細回路に向かって血液を連続的に流し入れ、
    　前記押圧機構は、前記往復機構が前記ピストンＡを押すのに合わせて、前記シリンジＢの有するピストンＢを押すことで前記シリンジＢから前記微細回路に向かって前記押圧液を連続的に流し入れ、
    　前記撹拌機構は磁石を有し、ここで前記シリンジＡ内に血液が蓄えられている間に、前記磁石が前記シリンジＡ内に配置された撹拌子を前記シリンジＡの外側から動かすことで前記シリンジＡ内の血液を撹拌する、
    　駆動装置。     A driving device for driving a fluid device
    The fluid device is
    A microcircuit for hydraulically classifying cells in blood,
    Blood intake and
    Syringe A for taking in and storing blood,
    A branch connecting the microcircuit, the intake, and the syringe A on three sides,
    A syringe B for storing the pressing liquid, which is connected to the microcircuit, and
    With
    The drive device
    The reciprocating mechanism includes a reciprocating mechanism, a pressing mechanism, a stirring mechanism, and a control unit for controlling their coordinated operation. The reciprocating mechanism pulls the piston A of the syringe A from the intake via the branch. Then, blood is taken into the syringe A, and by further pushing the piston A, blood is continuously flowed from the syringe A toward the microcircuit via the branch.
    In the pressing mechanism, the pressing liquid is continuously poured from the syringe B toward the microcircuit by pushing the piston B of the syringe B in accordance with the pushing of the piston A by the reciprocating mechanism.
    The stirring mechanism has a magnet, and while blood is stored in the syringe A, the magnet moves a stirrer arranged in the syringe A from the outside of the syringe A, thereby causing the syringe. Stir the blood in A,
    Drive device.
  2. 　前記駆動装置は前記往復機構と、前記押圧機構とが配置された取り付け面をさらに備え、
    　前記流体デバイスは血液中の細胞を分級する時に前記取り付け面に装着され、さらに血液の分級を終えた後に前記取り付け面から取り外される、平板状のカートリッジからなり、
    　前記カートリッジ中に、前記微細回路と、前記取入口と、前記シリンジＡと、前記分岐と、前記シリンジＢとが配置されており、
    　装着の際、前記カートリッジの背面が前記流体デバイスの前記取り付け面に対向するように向けられ、
    　前記磁石は前記シリンジＡに対向するとともに、前記取り付け面上を移動するように配置されている、
    　請求項１に記載の駆動装置。     The drive device further comprises a mounting surface on which the reciprocating mechanism and the pressing mechanism are arranged.
    The fluid device comprises a flat cartridge that is attached to the attachment surface when classifying cells in blood and is removed from the attachment surface after the blood has been classified.
    The microcircuit, the intake, the syringe A, the branch, and the syringe B are arranged in the cartridge.
    Upon mounting, the back of the cartridge is oriented so that it faces the mounting surface of the fluid device.
    The magnet is arranged so as to face the syringe A and move on the mounting surface.
    The drive device according to claim 1.
  3. 　前記往復機構は前記ピストンＡのピストンロッドを把持する連結部Ａと、前記連結部Ａを前記シリンジＡの長手方向に沿って往復運動させるアクチュエーターＡであって前記制御ユニットと接続するものと、前記ピストンＡのシリンダーを把持するホールド部とを有し、
    　前記磁石の後ろ側に前記アクチュエーターＡが配置されている、
    　請求項２に記載の駆動装置。     The reciprocating mechanism includes a connecting portion A that grips the piston rod of the piston A, an actuator A that reciprocates the connecting portion A along the longitudinal direction of the syringe A, and connects the connecting portion A to the control unit. It has a holding portion for gripping the cylinder of the piston A, and has a holding portion.
    The actuator A is arranged behind the magnet.
    The drive device according to claim 2.
  4. 　前記磁石は前記シリンジＡの長手方向に沿って前記撹拌子を前記シリンジＡ内で往復運動させる永久磁石であり、
    　前記撹拌機構は前記磁石の往復運動方向に対する側方から前記磁石を保持するアームと、前記アームを前記シリンジＡの長手方向に沿って往復運動させるアクチュエーターＭであって前記制御ユニットに接続するものとをさらに備える、
    　請求項３に記載の駆動装置。     The magnet is a permanent magnet that reciprocates the stirrer in the syringe A along the longitudinal direction of the syringe A.
    The stirring mechanism is an arm that holds the magnet from the side with respect to the reciprocating direction of the magnet, and an actuator M that reciprocates the arm along the longitudinal direction of the syringe A and is connected to the control unit. Further prepare,
    The drive device according to claim 3.
  5. 　前記流体デバイスが前記駆動装置に対して装着されているときに前記シリンジＡは吐出口を下に、前記ピストンＡを上にして立っており、
    　前記磁石の上方に前記往復機構の前記ホールド部が配置されており、
    　前記ホールド部の上方に前記往復機構の前記連結部Ａが配置されており、
    　前記撹拌機構は前記シリンジＡの前記シリンダーの下端まで前記往復運動する前記磁石を向かわせる、
    　請求項４に記載の駆動装置。     When the fluid device is attached to the drive, the syringe A stands with the discharge port down and the piston A up.
    The hold portion of the reciprocating mechanism is arranged above the magnet.
    The connecting portion A of the reciprocating mechanism is arranged above the holding portion.
    The stirring mechanism directs the reciprocating magnet to the lower end of the cylinder of the syringe A.
    The drive device according to claim 4.
  6. 　前記制御ユニットは、血液を前記シリンジＡ内に取り込み始めた時に、前記撹拌機構に前記磁石で前記シリンジＡ内の血液を撹拌させ始める、
    　請求項１に記載の駆動装置。     When the control unit starts to take blood into the syringe A, the control unit starts to cause the stirring mechanism to stir the blood in the syringe A with the magnet.
    The drive device according to claim 1.
  7. 　前記流体デバイスは、
    　　前記取入口を有する側と前記分岐に接続する側とを有する第１導管と、
    　　前記シリンジＡと前記分岐との間に位置する第２導管と、
    　　前記分岐と前記微細回路との間に位置する第３導管と、
    　をさらに備え、
    　前記駆動装置は、
    　　前記第１導管を閉鎖及び開放する取入バルブと、
    　　前記第３導管を閉鎖及び開放する開始バルブと、
    　をさらに備え、
    　前記制御ユニットは、前記往復機構が前記ピストンＡを引く時に、前記取入バルブに前記第１導管を開放させるとともに、前記開始バルブに前記第３導管を閉鎖させ、
    　前記制御ユニットは、前記往復機構が前記ピストンＡを押す時に、前記取入バルブに前記第１導管を閉鎖させるとともに、前記開始バルブに前記第３導管を開放させる、
    　請求項１に記載の駆動装置。     The fluid device is
    A first conduit having a side having the intake and a side connecting to the branch,
    A second conduit located between the syringe A and the branch,
    A third conduit located between the branch and the microcircuit,
    With more
    The drive device
    An intake valve that closes and opens the first conduit,
    A start valve that closes and opens the third conduit,
    With more
    The control unit causes the intake valve to open the first conduit and the start valve to close the third conduit when the reciprocating mechanism pulls the piston A.
    The control unit causes the intake valve to close the first conduit and the start valve to open the third conduit when the reciprocating mechanism pushes the piston A.
    The drive device according to claim 1.
  8. 　前記制御ユニットは前記協調動作のプログラムを記憶しており、前記プログラムから導き出されるタイムスケジュールに沿って、前記協調動作を自動実行する、
    　請求項１に記載の駆動装置。     The control unit stores the program of the cooperative operation, and automatically executes the cooperative operation according to the time schedule derived from the program.
    The drive device according to claim 1.
  9. 　請求項１に記載の前記駆動装置を備え、
    　さらに前記流体デバイスを備える、
    　血液内の細胞の分離装置。     The driving device according to claim 1 is provided.
    Further comprising the fluid device.
    A device for separating cells in the blood.
  10. 　請求項９に記載の分離装置で、血液内の細胞を分級する方法であって、
    　予め、
    　　前記シリンジＡ内に希釈液と前記撹拌子とを配置し、
    　　前記シリンジＢ内に押圧液を配置し、
    　　前記取入口に血液を蓄えた採血管を取り付け、
    　　前記微細回路の上面に前記分岐と前記シリンジＢとを接続し、
    　前記往復機構で、前記シリンジＡの有するピストンＡを引くことで、前記取入口から前記分岐を経由して前記シリンジＡ内に血液を取り込み、
    　前記撹拌機構で前記シリンジＡ内に配置された撹拌子を前記シリンジＡの外側から動かすことで前記シリンジＡ内の血液と希釈液とを混合撹拌し、
    　さらに前記ピストンＡを押すことで前記シリンジＡから前記分岐を経由して前記微細回路に向かって希釈された血液を連続的に流し入れ、
    　さらに前記往復機構が前記ピストンＡを押すのに合わせて、前記押圧機構で前記シリンジＢの有するピストンＢを押すことで前記シリンジＢから前記微細回路に向かって前記押圧液を連続的に流し入れ、
    　前記微細回路内で前記シリンジＡが作る血液の流れに対して、その側方より前記シリンジＢが作る押圧液の流れを接触させることで前記血液の流れを反対側に押し込み、
    　さらに前記押圧液の流れとは接触していない側にて前記血液の流れの中の細胞を水力学的に分級し、ここで分級される細胞は血球又は血球ではない浮遊細胞である、
    　前記微細回路の下面の排出口から分級された細胞を取り出す、
    　方法。     A method for classifying cells in blood by the separation device according to claim 9.
    In advance
    The diluent and the stirrer are placed in the syringe A.
    A pressing liquid is placed in the syringe B,
    A blood collection tube that stores blood is attached to the intake,
    The branch and the syringe B are connected to the upper surface of the microcircuit, and the branch is connected to the syringe B.
    By pulling the piston A of the syringe A with the reciprocating mechanism, blood is taken into the syringe A from the intake via the branch.
    By moving the stirrer arranged in the syringe A from the outside of the syringe A by the stirring mechanism, the blood in the syringe A and the diluent are mixed and stirred.
    Further, by pushing the piston A, diluted blood is continuously poured from the syringe A toward the microcircuit via the branch.
    Further, as the reciprocating mechanism pushes the piston A, the pressing mechanism pushes the piston B of the syringe B to continuously flow the pressing liquid from the syringe B toward the microcircuit.
    By contacting the flow of the pressing liquid produced by the syringe B from the side with respect to the blood flow produced by the syringe A in the microcircuit, the blood flow is pushed to the opposite side.
    Further, the cells in the blood flow are hydraulically classified on the side not in contact with the flow of the pressing liquid, and the cells classified here are blood cells or floating cells that are not blood cells.
    The classified cells are taken out from the outlet on the lower surface of the microcircuit.
    Method.
  11. 　前記駆動装置は繰り返し使用する一方で、前記流体デバイスを使い捨て交換することで、
    　血液のサンプルごとにクリーンな流体デバイスを用いて血液内の細胞を分級する、
    　請求項１０に記載の方法。     While the drive device is used repeatedly, the fluid device is disposable and replaced.
    Classify cells in blood using a clean fluid device for each blood sample,
    The method according to claim 10.
  12. 　血液中の細胞を水力学的に分級するための微細回路と分級前の血液を蓄えるためのリザーバーとシリンジとの組み合わせを駆動するための駆動装置であって、
    　前記シリンジは少なくとも、血液を取り込むとともに蓄えるためのシリンジＡと、押圧液を蓄えるためのシリンジであって前記微細回路の他の入口に接続するシリンジＢと、を含み、
    　前記駆動装置は、
    　往復機構と、装着機構と、押圧機構と、撹拌機構と、これらの協調動作を制御する制御ユニットと、を備え
    　前記往復機構は、前記シリンジＡの有するピストンＡを引くことで、前記シリンジＡ内に向かって、前記リザーバーから血液を取り込み、
    　前記装着機構は、前記シリンジＡの吐出口を前記微細回路の入口に装着し、
    　前記往復機構は、前記ピストンＡを押すことで前記シリンジＡから前記吐出口及び前記入口を経由して前記微細回路に向かって血液を連続的に流し入れ、
    　前記押圧機構は、前記往復機構が前記ピストンＡを押すのに合わせて、前記シリンジＢの有するピストンＢを押すことで前記シリンジＢから前記微細回路に向かって前記押圧液を連続的に流し入れ、
    　前記撹拌機構は磁石を有し、ここで前記シリンジＡ内に血液が蓄えられている間に、前記磁石が前記シリンジＡ内に配置された撹拌子を前記シリンジＡの外側から動かすことで前記シリンジＡ内の血液を撹拌する、
    　駆動装置。     A drive device for driving a combination of a microcircuit for hydraulically classifying cells in blood and a reservoir and a syringe for storing pre-classified blood.
    The syringe comprises at least a syringe A for taking in and storing blood and a syringe B for storing pressing fluid and connected to another inlet of the microcircuit.
    The drive device
    A reciprocating mechanism, a mounting mechanism, a pressing mechanism, a stirring mechanism, and a control unit for controlling their cooperative operation are provided. The reciprocating mechanism is provided in the syringe A by pulling the piston A of the syringe A. Takes blood from the reservoir towards
    The mounting mechanism mounts the discharge port of the syringe A at the inlet of the microcircuit.
    By pushing the piston A, the reciprocating mechanism continuously flows blood from the syringe A toward the microcircuit via the discharge port and the inlet.
    In the pressing mechanism, the pressing liquid is continuously poured from the syringe B toward the microcircuit by pushing the piston B of the syringe B in accordance with the pushing of the piston A by the reciprocating mechanism.
    The stirring mechanism has a magnet, and while blood is stored in the syringe A, the magnet moves a stirrer arranged in the syringe A from the outside of the syringe A, thereby causing the syringe. Stir the blood in A,
    Drive device.
  13. 　請求項１２に記載の駆動装置と前記微細回路と前記リザーバーと前記シリンジとで、前記リザーバーに蓄えられた血液内の細胞を分級する方法であって、
    　予め、
    　　前記シリンジＡ内に希釈液と前記撹拌子を配置し、
    　　前記シリンジＢ内に押圧液を配置し、
    　　前記リザーバーに血液を蓄え、
    　　前記微細回路の上面に前記シリンジＢを接続し、
    　前記往復機構で、前記シリンジＡの有するピストンＡを引くことで、前記リザーバーから前記シリンジＡ内に血液を取り込み、
    　前記装着機構で、前記シリンジＡの前記吐出口を前記微細回路の前記入口に装着し、
    　前記撹拌機構で前記シリンジＡ内に配置された撹拌子を前記シリンジＡの外側から動かすことで前記シリンジＡ内の血液と希釈液とを混合撹拌し、
    　さらに前記ピストンＡを押すことで前記シリンジＡから前記吐出口及び前記入口を経由して前記微細回路に向かって希釈された血液を連続的に流し入れ、
    　さらに前記往復機構が前記ピストンＡを押すのに合わせて、前記押圧機構で前記シリンジＢの有するピストンＢを押すことで前記シリンジＢから前記微細回路に向かって前記押圧液を連続的に流し入れ、
    　前記微細回路内で前記シリンジＡが作る血液の流れに対して、その側方より前記シリンジＢが作る押圧液の流れを接触させることで前記血液の流れを反対側に押し込み、
    　さらに前記押圧液の流れとは接触していない側にて前記血液の流れの中の細胞を水力学的に分級し、ここで分級される細胞は血球又は血球ではない浮遊細胞である、
    　前記微細回路の下面の排出口から分級された細胞を取り出す、
    　方法。     A method for classifying cells in blood stored in the reservoir by the driving device, the microcircuit, the reservoir, and the syringe according to claim 12.
    In advance
    The diluent and the stirrer are placed in the syringe A.
    A pressing liquid is placed in the syringe B,
    Blood is stored in the reservoir,
    The syringe B is connected to the upper surface of the microcircuit,
    By pulling the piston A of the syringe A with the reciprocating mechanism, blood is taken into the syringe A from the reservoir.
    With the mounting mechanism, the discharge port of the syringe A is mounted at the inlet of the microcircuit.
    By moving the stirrer arranged in the syringe A from the outside of the syringe A by the stirring mechanism, the blood in the syringe A and the diluent are mixed and stirred.
    Further, by pushing the piston A, diluted blood is continuously poured from the syringe A toward the microcircuit via the discharge port and the inlet.
    Further, as the reciprocating mechanism pushes the piston A, the pressing mechanism pushes the piston B of the syringe B to continuously flow the pressing liquid from the syringe B toward the microcircuit.
    The blood flow is pushed to the opposite side by bringing the flow of the pressing liquid produced by the syringe B into contact with the blood flow created by the syringe A in the microcircuit.
    Further, the cells in the blood flow are hydraulically classified on the side not in contact with the flow of the pressing liquid, and the cells classified here are blood cells or floating cells that are not blood cells.
    The classified cells are taken out from the outlet on the lower surface of the microcircuit.
    Method.
PCT/JP2020/013180 2019-03-29 2020-03-25 Apparatus for driving combination of microcircuit and syringe WO2020203510A1 (en)

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6274369A (en) * 1985-09-30 1987-04-06 日機装株式会社 Syringe pump
JPH11322618A (en) * 1998-05-13 1999-11-24 Asahi Medical Co Ltd Separation and collection of nucleated cell, and liquid containing nucleated cell
JP2011013208A (en) * 2009-06-05 2011-01-20 Advance Co Ltd Biological operation system and industrial operation system
JP2011088869A (en) * 2009-10-26 2011-05-06 Osaka Univ Method for recovering leukocyte protein and recovery apparatus
JP2018102242A (en) * 2016-12-27 2018-07-05 株式会社 ＴＬ Ｇｅｎｏｍｉｃｓ Method for obtaining fetal cell chromosomal dnas
WO2020036115A1 (en) * 2018-08-14 2020-02-20 株式会社 ＴＬ Ｇｅｎｏｍｉｃｓ Fluid device

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6274369A (en) * 1985-09-30 1987-04-06 日機装株式会社 Syringe pump
JPH11322618A (en) * 1998-05-13 1999-11-24 Asahi Medical Co Ltd Separation and collection of nucleated cell, and liquid containing nucleated cell
JP2011013208A (en) * 2009-06-05 2011-01-20 Advance Co Ltd Biological operation system and industrial operation system
JP2011088869A (en) * 2009-10-26 2011-05-06 Osaka Univ Method for recovering leukocyte protein and recovery apparatus
JP2018102242A (en) * 2016-12-27 2018-07-05 株式会社 ＴＬ Ｇｅｎｏｍｉｃｓ Method for obtaining fetal cell chromosomal dnas
WO2020036115A1 (en) * 2018-08-14 2020-02-20 株式会社 ＴＬ Ｇｅｎｏｍｉｃｓ Fluid device

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