WO2015193958A1 - 分注チップ装着用ヘッド装置及びこれを用いた移動装置 - Google Patents
分注チップ装着用ヘッド装置及びこれを用いた移動装置 Download PDFInfo
- Publication number
- WO2015193958A1 WO2015193958A1 PCT/JP2014/065970 JP2014065970W WO2015193958A1 WO 2015193958 A1 WO2015193958 A1 WO 2015193958A1 JP 2014065970 W JP2014065970 W JP 2014065970W WO 2015193958 A1 WO2015193958 A1 WO 2015193958A1
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- WIPO (PCT)
- Prior art keywords
- dispensing tip
- frame
- head
- head device
- tip mounting
- Prior art date
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
- G01N35/1011—Control of the position or alignment of the transfer device
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/02—Burettes; Pipettes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/02—Burettes; Pipettes
- B01L3/021—Pipettes, i.e. with only one conduit for withdrawing and redistributing liquids
- B01L3/0217—Pipettes, i.e. with only one conduit for withdrawing and redistributing liquids of the plunger pump type
- B01L3/0227—Details of motor drive means
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/02—Burettes; Pipettes
- B01L3/021—Pipettes, i.e. with only one conduit for withdrawing and redistributing liquids
- B01L3/0217—Pipettes, i.e. with only one conduit for withdrawing and redistributing liquids of the plunger pump type
- B01L3/0231—Pipettes, i.e. with only one conduit for withdrawing and redistributing liquids of the plunger pump type having several coaxial pistons
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/02—Burettes; Pipettes
- B01L3/0275—Interchangeable or disposable dispensing tips
- B01L3/0279—Interchangeable or disposable dispensing tips co-operating with positive ejection means
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/02—Devices for withdrawing samples
- G01N1/10—Devices for withdrawing samples in the liquid or fluent state
- G01N1/14—Suction devices, e.g. pumps; Ejector devices
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/02—Adapting objects or devices to another
- B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
- B01L2400/0478—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure pistons
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/08—Regulating or influencing the flow resistance
- B01L2400/082—Active control of flow resistance, e.g. flow controllers
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N2035/1027—General features of the devices
- G01N2035/103—General features of the devices using disposable tips
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N35/1081—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices characterised by the means for relatively moving the transfer device and the containers in an horizontal plane
Definitions
- the present invention relates to a head device to which a dispensing tip for sucking a liquid containing an object such as a cell aggregate, for example, and discharging the sucked liquid is mounted, and an object moving device using the head device.
- a dispensing operation is performed in which an appropriate amount of cell culture solution is collected from a tube storing a cell culture solution in which a large amount of cell aggregates are dispersed and transferred to another dish.
- a dispensing tip that sucks the cell culture solution from the tube and discharges it to another dish is used.
- an operation for selecting a cell aggregate of a desired size from a cell culture solution containing cell aggregates and contaminants of various sizes is performed.
- Patent Document 1 discloses a technique in which a cell aggregate is used as a moving object, the cell aggregate is sucked from a dispensing well using a suction tip (micropipette), and the cell aggregate is discharged to a cell petri dish. .
- the cell aggregate is held in a liquid, and the tip opening of the suction tip is immersed in the liquid during the suction. For this reason, the suction tip may have to be disposed of after the completion of one suction and discharge.
- An object of the present invention is to provide a head device that can highly automate the work of sucking an object using a dispensing tip and discharging the sucked object, and an object moving device using the head device. is there.
- a dispensing tip mounting head device is a head device to which a dispensing tip for sucking a liquid containing an object and discharging the sucked liquid is attached, and includes a piston member, A first shaft member that engages the piston member and moves the piston member in a vertical direction; and a cylindrical space that includes a cylinder space that movably accommodates the piston member in a vertical direction.
- a cylindrical rod having a tip mounting portion into which a base end portion is fitted at a lower end, a first frame on which the first shaft member and the cylindrical rod are mounted, and the first frame are engaged, and the first A second shaft member that moves the frame in the vertical direction and a second guide member that is mounted with the second shaft member and guides the vertical movement of the cylindrical rod accompanying the vertical movement of the first frame.
- a shaft control unit that controls the operation of the first shaft member and the second shaft member, the shaft control unit, in a state where the dispensing tip is mounted on the tip mounting unit, By moving the piston member in the vertical direction, the first control for controlling the first shaft member so that the liquid is sucked and discharged by the dispensing tip, and by moving the first frame in the upward direction, And a second control for controlling the second shaft member to cause the guide portion and the proximal end portion of the dispensing tip to interfere with each other and to disengage the dispensing tip from the tip mounting portion.
- a moving device includes a dispensing tip mounting head device, a first container that stores an object, a second container that receives the object, and the head device that includes the first container. And a head moving mechanism for moving in a horizontal direction between the first container and the second container.
- FIG. 1 is a perspective view showing an appearance of a head device according to an embodiment of the present invention.
- FIG. 2 is an enlarged perspective view of a main part of FIG.
- FIG. 3 is a side sectional view of the head device.
- FIG. 4 is a perspective view of the head device, showing a state where the head (cylindrical rod) is raised in the Z-axis direction.
- FIG. 5 is a perspective view of the head device, showing a state where the head is lowered in the Z-axis direction.
- FIG. 6 is a cross-sectional view of a dispensing tip.
- FIG. 7A is a schematic diagram showing a cell culture solution suction operation by the dispensing tip
- FIG. 7B is a schematic diagram showing a discharge operation.
- FIG. 8A to 8D are perspective views for explaining the attaching / detaching operation of the dispensing tip to the head.
- FIG. 9 is a perspective view showing the head device in a state where the piston member is raised.
- FIG. 10 is a cross-sectional view of the head device in the state shown in FIG.
- FIG. 11 is a perspective view showing the head device in a state where the piston member is lowered.
- 12 is a cross-sectional view of the head in the state shown in FIG.
- FIG. 13 is a perspective view showing a state immediately before the dispensing tip is detached from the head by the guide portion.
- FIG. 14 is a block diagram illustrating a control configuration of the head device.
- FIG. 15 is a perspective view of a cell moving device to which the head device is applied.
- FIG. 16 is a perspective view of the head unit.
- FIG. 17 is a perspective view showing components of a cell movement line in the cell movement device.
- an object to be sucked and discharged by a dispensing tip is a cell culture solution containing cells derived from a living body, particularly a cell aggregate.
- the liquid is not limited to the cell culture solution, and may be a medical liquid containing various objects, a food industry liquid, an industrial liquid, or the like.
- FIG. 1 is a perspective view showing an appearance of a head device 1 according to an embodiment of the present invention
- FIG. 2 is an enlarged perspective view of a main part of FIG. 1
- FIG. 3 is a side sectional view of the head device 1.
- the head device 1 is a device to which a dispensing chip 80 for aspirating a cell culture solution (liquid containing an object) containing cell aggregates and discharging the aspirated cell culture solution is mounted.
- the head device 1 includes a first ball screw device 10 (first shaft member), a piston member 14 moved in the vertical direction (Z direction) by the first ball screw device 10, and a head to which a dispensing tip 80 is mounted.
- the first ball screw device 10 is engaged with the piston member 14 and moves the piston member 14 in the vertical direction.
- the first ball screw device 10 includes a first motor 11, a coupling 111, an upper end bearing 112, a first screw shaft 12, and a first nut member 13 arranged in the Z direction.
- the first motor 11 is a motor that generates a rotational driving force for rotating the first screw shaft 12 forward and backward around the axis.
- the coupling 111 is a member that connects the output shaft of the first motor 11 and the upper end of the first screw shaft 12.
- the upper end bearing 112 rotatably supports the upper end of the first screw shaft 12.
- the first screw shaft 12 extends in the Z direction, and a male screw is engraved on the peripheral surface.
- the first nut member 13 has a female screw on the inner surface and is engaged with the first screw shaft 12. When the first screw shaft 12 rotates forward or backward, the first nut member 13 moves upward (+ Z) or downward ( ⁇ Z). The piston member 14 is engaged with the first nut member 13.
- the piston member 14 is a member that is long in the Z direction, and has an upper end portion 141, a lower end portion 143, and an intermediate portion 142 between the upper end portion 141 and the lower end portion 143.
- the upper end 141 is a cylindrical portion having a larger diameter than the intermediate portion 142 and the lower end 143, and the first nut member is formed on the inner peripheral surface thereof. 13 is provided with an engaging portion (threaded portion) fixed to 13.
- the first nut member 13 includes a cylindrical portion on the ⁇ Z side and a flange portion on the + Z side.
- the first nut member 13 is screwed to the upper end portion 141 in a state where the cylindrical portion is fitted in the cylinder of the upper end portion 141 and the flange portion is held on the upper surface of the upper end portion 141. Accordingly, the piston member 14 moves in the vertical direction in conjunction with the vertical movement of the first nut member 13.
- the lower end portion 143 is a columnar portion accommodated in a cylinder space 15H of the head 15 described below, and a seal member 144 is provided on the peripheral surface thereof.
- the seal member 144 is a resin seal ring, and is fitted in a seal groove provided on the peripheral surface near the lower end surface of the piston member 14.
- the intermediate portion 142 is a cylindrical portion having the same outer diameter as that of the lower end portion 143, and has an accommodation space 14H for accommodating the first screw shaft 12 therein.
- the accommodation space 14 ⁇ / b> H is a cylindrical space extending in the Z direction, and has an inner diameter that is slightly larger than the outer diameter of the first screw shaft 12. In a state where the first nut member 13 has moved downward (FIGS.
- the first screw shaft 12 fits relatively shallowly into the accommodation space 14H (see also FIG. 12).
- the first nut member 13 is moved upward (FIGS. 3 and 10)
- the first screw shaft 12 is fitted relatively deeply into the accommodation space 14H.
- the head 15 is a cylindrical member fixed to the first frame 21 and immovable with respect to the piston member 14.
- the head 15 includes a head main body 150 (rod main body) including a first portion 151 and a second portion 152 that are continuous in the vertical direction, and an exchange portion 153 that is detachably attached to the lower end of the head main body 150. ing.
- the first portion 151 includes a cylinder space 15H that accommodates the lower end portion 143 of the piston member 14 so as to be movable in the vertical direction.
- the cylinder space 15H is a cylindrical space having an inner diameter slightly larger than the outer diameter of the lower end portion 143.
- the seal member 144 is in slidable contact with the inner wall surface of the first portion 151 that defines the cylinder space 15H.
- the second portion 152 communicates with the cylinder space 15H and includes a cylindrical space 152H having an inner diameter smaller than that of the cylinder space 15H.
- the exchange unit 153 includes a cylindrical space 152H and a cylindrical space 153H communicating with the cylinder space 15H inside, and an upper end thereof is screw-connected to a lower end of the second portion 152.
- the outer peripheral surface near the lower end of the replacement part 153 is a chip mounting part 153A to which the dispensing chip 80 is fitted and mounted (see FIG. 6).
- the second ball screw device 30 is a shaft member for moving the first frame 21 on which the first ball screw device 10 and the head 15 are mounted in the vertical direction.
- the second ball screw device 30 includes a second motor 31, a coupling 311, an upper end bearing 312, a second screw shaft 32, and a second nut member 33 arranged in the Z direction.
- the second motor 31 is a motor that generates a rotational driving force for rotating the second screw shaft 32 forward and backward around the axis.
- the coupling 311 is a member that connects the output shaft of the second motor 31 and the upper end of the second screw shaft 32.
- the upper end bearing 312 rotatably supports the upper end of the second screw shaft 32.
- the second screw shaft 32 extends in the Z direction, and a male screw is engraved on the peripheral surface.
- the second nut member 33 has an internal thread on the inner surface and is engaged with the second screw shaft 32. When the second screw shaft 32 rotates forward or backward, the second nut member 33 moves upward (+ Z) or downward ( ⁇ Z).
- the first frame 21 is fixed to the second nut member 33.
- the first frame 21 plays a role of holding the head 15 in a fixed manner, a role of moving the head 15 in the vertical direction by interlocking with the second nut member 33, and a role of holding the first ball screw device 10.
- the first frame 21 includes a main frame portion 211, a lower frame portion 212 protruding in the ⁇ X direction from below the main frame portion 211, an upper frame portion 213 protruding in the ⁇ X direction from above the main frame portion 211, a main frame portion 211, a guided portion 214 is provided on the side surface in the + X direction.
- the main frame portion 211 includes a hole through which the second screw shaft 32 penetrates in the vertical direction.
- a holding hole 211 ⁇ / b> A for holding the second nut member 33 is formed at the upper end of the main frame portion 211.
- the second nut member 33 includes a cylindrical portion on the ⁇ Z side and a flange portion on the + Z side. The second nut member 33 is screwed to the main frame portion 211 in a state where the cylindrical portion is fitted into the holding hole 211A and the flange portion is held on the upper surface of the main frame portion 211. Accordingly, the first frame 21 moves in the vertical direction in conjunction with the movement of the second nut member 33 in the vertical direction.
- the lower frame part 212 is a part for holding the upper end part of the head 15 in a fixed manner.
- a longitudinal groove having a semicircular cross section that can accommodate the + X side half surface of the head 15 is provided.
- a holding piece 215 having a longitudinal groove having a similar semicircular cross section is attached to the half surface on the ⁇ X side of the head 15.
- the upper frame part 213 is provided with a hole through which the intermediate part 142 of the piston member 14 penetrates in the vertical direction.
- a holding frame 23 for holding the first ball screw device 10 is erected from an end portion on the ⁇ X side of the upper frame portion 213. As shown in FIG. 2, the holding frame 23 includes a vertical frame 231, and an upper frame 232 and a lower frame 233 that protrude in the + X direction from the upper end of the vertical frame 231.
- a guide rail 234 (FIG. 10) extending in the vertical direction is attached to the vertical frame 231.
- a guided portion 145 attached to the upper end portion 141 of the piston member 14 is engaged with the guide rail 234.
- the piston member 14 moves up and down while being guided by the guide rail 234 when the first nut member 13 moves up and down.
- the first motor 11 is fixed to the upper frame 232.
- An upper end bearing 112 is fixed to the lower frame 233.
- the second frame 22 has a role of holding the second ball screw device 30, a role of guiding the vertical movement of the first frame 21, and a role of guiding the vertical movement of the head 15.
- the second frame 22 includes a vertical frame 221, a horizontal frame 225 protruding in the ⁇ X direction from the lower end 224 of the vertical frame 221, and an arm member 24 (guide) protruding in the ⁇ Z direction from the lower surface of the horizontal frame 225. Part).
- the vertical frame 221 is a rectangular frame extending in the vertical direction, and a guide rail 222 extending in the vertical direction is attached to the side surface on the ⁇ X side.
- the above-described guided portion 214 of the first frame 21 is fitted into the guide rail 222.
- the first frame 21 can move in the vertical direction while being guided along the guide rail 222 when the second ball screw device 30 is driven.
- An L-shaped frame 226 that holds the upper end bearing 312 is attached to the upper end 223 of the vertical frame 221.
- a holding frame 227 for holding the second motor 31 is fixed to the upper end of the L-shaped frame 226.
- the horizontal frame 225 is a rectangular frame extending in the X direction, and includes a bearing portion 251 that rotatably supports the lower end of the second screw shaft 32, and a through hole 252 that allows the head 15 to pass through in the vertical direction.
- the arm member 24 is assembled to the lower surface of the horizontal frame 225 by screws 253 (FIG. 10).
- the arm member 24 guides the vertical movement of the head 15 (head main body 150) accompanying the vertical movement of the first frame 21.
- the arm member 24 also functions to detach the dispensing tip 80 attached to the head 15 from the head portion 15. This will be described in detail later.
- the arm member 24 includes a guide plate 242 including a U-shaped guide recess 241 that opens in the ⁇ X direction, and a vertical arm 243.
- the guide plate 242 is a plate material extending in the horizontal direction.
- the opening width in the Y direction of the guide recess 241 and the semicircular surface of the bottom of the U-shaped opening have a width and an inner diameter that are slightly larger than the outer diameter of the head 15 having a cylindrical shape. Therefore, the guide recess 241 can be fitted into the head 15 from the side.
- the vertical arm 243 is a plate member that protrudes downward from the lower surface of the horizontal frame 225.
- the + X direction end of the guide plate 242 is fixed to the lower end surface of the vertical arm 243 with a screw 253.
- the screw 253 passes through the guide plate 242 and the vertical arm 243 from the bottom to the top, and is screwed into a screw hole formed on the lower surface of the horizontal frame 225.
- FIG. 4 is a perspective view of the head device 1 and shows a state in which the head 15 is raised in the + Z direction.
- the first frame 21 is raised relative to the second frame 22 by driving the second ball screw device 30. That is, the first frame 21 is located near the upper limit of + Z of the movable range along the guide rail 222. Accordingly, the first ball screw device 10 and the head 15 held by the first frame 21 are also raised.
- a bending protection member 25 that protects the power supply cable of the first motor 11 is added.
- the bending protection member 25 is a portion that is convexly curved upward, and deforms following the vertical movement of the first frame 21.
- the height position in the Z direction of the dispensing tip 80 attached to the lower end of the head 15 is also raised.
- the upper end of the dispensing tip 80 is located in the immediate vicinity below the arm member 24.
- the dispensing tip 80 is disposed at such a height position, for example, after the suction of the cell culture solution in which the cell agglomerates are dispersed, the head device 1 moves in the XY direction to the disposition position of the dish serving as a discharge destination. When it is moved to.
- FIG. 5 is a diagram showing a state in which the head 15 is lowered in the ⁇ Z direction.
- the first frame 21 is positioned in the vicinity of the ⁇ Z lower limit of the movable range along the guide rail 222 and is close to the lateral frame 225 of the second frame 22.
- the first ball screw device 10 and the head 15 are also lowered.
- the head 15 reaches a state where it protrudes greatly downward from the horizontal frame 225.
- the height position in the Z direction of the dispensing tip 80 is also lowered.
- the dispensing tip 80 is disposed at such a lowered position, for example, when the cell culture solution is aspirated from the tube storing the cell culture solution with the dispensing tip 80 or the aspirated cell culture solution is This is when discharging to other dishes.
- FIG. 6 is a cross-sectional view of the dispensing tip 80 attached to the head 15.
- the dispensing tip 80 is an elongated tube-like member, and includes a proximal end portion 81 fitted into the head 15 (exchanger 153), and a distal end portion 82 provided with an opening 80T for sucking and discharging the cell culture solution at the lower end edge. And an intermediate portion 83 extending between the two.
- the intermediate portion 83 has a tapered shape in which the outer diameter gradually decreases from the proximal end portion 81 side toward the distal end portion 82 side.
- An air filter may be incorporated in the base end portion 81.
- the dispensing tip 80 can be attached to and detached from the tip attachment portion 153A of the replacement portion 153.
- the chip mounting portion 153 ⁇ / b> A is an outer peripheral surface near the lower end of the replacement portion 153.
- the inside of the dispensing tip 80 is provided with a tubular space 80H that can accommodate a liquid containing the object.
- the tubular space 80H communicates with the cylindrical space 153H in the replacement portion 153 of the head 15, the cylindrical space 152H in the second portion 152, and the cylinder space 15H in the first portion 151. Therefore, a suction force is generated in the tubular space 80H by the upward movement of the piston member 14, and a discharge force is generated in the tubular space 80H by the downward movement of the piston member 14.
- the dispensing chip 80 sucks the cell culture solution from the opening 80T when the suction force is applied, and discharges the cell culture solution sucked by the discharge force from the opening 80T.
- FIG. 7 (A) and 7 (B) are diagrams schematically showing the suction and discharge operations of the cell culture solution Lm containing the cell aggregate C by the dispensing tip 80.
- FIG. Here, the case where the dispensing tip 80 sucks the cell culture solution Lm (cell aggregate C) stored in the first container C1 and discharges the sucked cell culture solution Lm to the second container C2 is illustrated. is doing.
- 7A shows a suction operation in which the dispensing tip 80 sucks the cell culture solution Lm from the first container C1
- FIG. 7B shows a sucking operation of the cell culture solution Lm in the second container.
- movement discharged to C2 is shown, respectively.
- the head device 1 When the suction operation in FIG. 7A is performed, first, the head device 1 is aligned so that the dispensing tip 80 is positioned above the first container C1. Thereafter, the head 15 is lowered by driving the second ball screw device 30 as shown in FIG. This lowering is performed until the opening 80T at the lower end of the dispensing tip 80 reaches below the liquid level of the cell culture solution Lm stored in the first container C1. Thereafter, the piston member 14 is raised by driving the first ball screw device 10, and a suction force is generated in the tubular space 80H. By this suction force, a suction fluid flow indicated by an arrow a1 is generated in the vicinity of the opening 80T, and the cell culture solution Lm is sucked into the tubular space 80H. The symbol Lma in the figure indicates the cell culture solution sucked into the tubular space 80H. After this suction operation, the head 15 is raised by driving the second ball screw device 30 as shown in FIG.
- the head device 1 is moved in the XY direction so that the dispensing tip 80 is positioned above the second container C2. Thereafter, the head 15 is lowered by driving the second ball screw device 30. This lowering is performed until the opening 80T of the dispensing tip 80 enters the cavity of the second container C2. Thereafter, the piston member 14 is lowered by driving the first ball screw device 10, and a discharge force is generated in the tubular space 80H. With this suction force, the cell culture solution Lma held in the tubular space 80H is discharged from the opening 80T as indicated by an arrow a2, and the cell culture solution Lm is stored in the second container C2.
- FIGS. 8A to 8D are perspective views for explaining the attaching / detaching operation of the dispensing tip 80 to the tip mounting portion 153A of the head 15 (exchanger 153).
- the head 15 When the dispensing tip 80 is attached to the tip attaching portion 153A, as shown in FIG. 8A, the head 15 is positioned above one dispensing tip 80 in the standing state. Then, the head 15 is lowered by driving the second ball screw device 30. By this lowering, the tip mounting portion 153A of the head 15 is fitted into the proximal end portion 81 of the dispensing tip 80 as shown in FIG. FIG. 8C shows a state in which the head 15 to which the dispensing tip 80 is attached is raised by driving the second ball screw device 30.
- the second ball screw device 30 does not pull the dispensing tip 80 further upward than the state of FIG.
- the head 15 is further lifted upward as shown in FIG.
- the lower end surface of the guide plate 242 and the upper end edge of the dispensing tip 80 interfere with each other. Due to the interference, the dispensing tip 80 is gradually removed from the tip mounting portion 153A, and finally the dispensing tip 80 is detached from the tip mounting portion 153A.
- FIG. 9 is a perspective view showing the head device 1 in a state where the piston member 14 is raised for the suction operation shown in FIG. 7A
- FIG. 10 is a cross-sectional view of the head device 1 in the state shown in FIG. FIG.
- FIG. 11 is a perspective view showing the head device 1 in a state where the piston member 14 is lowered for the discharge operation shown in FIG. 7B
- FIG. 12 is a cross-sectional view of the head device 1 in the state shown in FIG. FIG.
- the first screw shaft 12 is rotationally driven by the first motor 11 so that the first nut member 13 moves upward.
- the first frame 21 at this time is set at the lowest position in the movement range and is not moved.
- the piston member 14 fixed to the first nut member 13 is also raised integrally.
- the accommodation space 14 ⁇ / b> H of the piston member 14 functions as an escape hole for the first screw shaft 12.
- the length in the Z direction of the accommodation space 14 ⁇ / b> H including the in-cylinder space of the upper end portion 141 is set to be slightly longer than the first screw shaft 12.
- FIGS. 9 and 10 show a state in which the first nut member 13 is moving upward most within the movable range along the first screw shaft 12.
- the first screw shaft 12 is deeply fitted into the accommodation space 14H, and the distance between the lower end 12B of the first screw shaft 12 and the bottom surface 146 of the accommodation space 14H is the shortest.
- the first screw shaft 12 is rotationally driven by the first motor 11 so that the first nut member 13 moves downward.
- the piston member 14 integrated with the first nut member 13 is also lowered.
- the first screw shaft 12 gradually comes out of the accommodation space 14H of the piston member 14.
- 11 and 12 show a state in which the first nut member 13 is moving downward most in the movable range along the first screw shaft 12. In this state, the first screw shaft 12 is most shallowly fitted in the accommodation space 14H, and the distance between the lower end 12B of the first screw shaft 12 and the bottom surface 146 of the accommodation space 14H is the longest.
- the lower end portion 143 of the piston member 14 moves downward in the cylinder space 15H.
- the air in the cylinder space 15H is pressurized. Therefore, the cell culture solution held in the tubular space 80H is discharged from the dispensing tip 80 by the applied pressure.
- FIG. 13 is a perspective view showing a state immediately before the dispensing tip 80 is detached from the head 15 by the arm member 24.
- the guide plate 242 of the arm member 24 is a portion that guides the movement of the head 15 in the vertical direction, and includes a guide recess 241 having an opening width slightly larger than the outer diameter of the head 15. Yes.
- the opening width of the guide recess 241 is smaller than the outer diameter of the dispensing tip 80 attached to the tip attachment portion 153A. Accordingly, the lower end surface 242B of the guide plate 242 and the upper end edge 81A of the base end portion 81 of the dispensing tip 80 face each other in the state of FIG.
- the lower end surface 242B of the guide plate 242 starts to contact (interfere) with the upper end edge 81A of the dispensing tip 80.
- the dispensing tip 80 is only fitted in the tip mounting portion 153A, and is not bonded or the like. Therefore, as the head 15 is raised, the upper end edge 81A is pressed against the lower end surface 242B, and the base end portion 81 is gradually removed from the chip mounting portion 153A.
- FIG. 14 is a block diagram showing a control configuration of the head device 1.
- the head device 1 controls the driving of the first ball screw device 10 and the second ball screw device 30 and controls the movement of the head device 1 itself in the X, Y, and Z directions.
- the unit 300 is provided.
- the axis control unit 300 includes the first motor 11 and the second motor 31 described above, and an X-axis motor 302 and a Y-axis motor 301 (not shown in the above figure) (the head device 1 is moved in the horizontal direction).
- the head moving mechanism ).
- the axis control unit 300 performs the following first control and second control in a state where the dispensing tip 80 is mounted on the tip mounting unit 153A of the head 15.
- the first ball screw device 10 is controlled so that the cell culture solution containing cell aggregates is sucked and discharged by the dispensing tip 80 by the movement of the piston member 14 in the vertical direction (FIG. 7A). FIG. 7B and FIGS. 9 to 12).
- the upward movement of the first frame 21 causes the arm member 24 (guide portion) and the base end portion 81 of the dispensing tip 80 to interfere, and the dispensing tip 80 is detached from the tip mounting portion 153A.
- the second ball screw device 30 is controlled so as to be controlled (see FIGS. 8A to 8D and FIG. 13).
- the axis controller 300 attaches the dispensing tip 80 to the tip attachment portion 153 ⁇ / b> A of the head 15 by moving downward in the first frame 21.
- the mounting control for controlling the second ball screw device 30 is also executed.
- the first motor 11 rotates the first screw shaft 12 to move the piston member 14 integrated with the first nut member 13 up and down, and as described above, the cell culture solution (object) by the dispensing tip 80.
- the suction and discharge are performed.
- the second motor 31 rotates the second screw shaft 32 to move the first frame 21 on which the head 15 is mounted in the Z direction.
- the X-axis motor 302 is mounted on an X guide frame (not shown) that guides the movement of the head device 1 in the X direction, and moves the head device 1 in the X direction.
- the Y-axis motor 301 is mounted on a Y guide frame (not shown) that guides the movement of the head device 1 in the Y direction, and moves the head device 1 in the Y direction.
- the shaft control unit 300 controls the vertical movement of the first nut member 13 by controlling the driving of the first motor 11, thereby executing the first control.
- the shaft controller 300 rotates the first motor 11 in the forward direction for a predetermined time to raise the piston member 14 by a predetermined distance, and sucks a predetermined amount of cell culture solution into the dispensing tip 80.
- the shaft control unit 300 rotates the first motor 11 in the reverse direction for a predetermined time to lower the piston member 14 by a predetermined distance, and discharges the cell culture solution held in the dispensing tip 80. Let The suction speed or the discharge speed is controlled by the rotation speed of the first motor 11.
- the shaft control unit 300 controls the height position of the first frame 21, that is, the head 15 in the Z direction by controlling the driving of the second motor 31.
- the axis control unit 300 rotates the second motor 31 in the forward direction or the reverse direction for a predetermined time to move the head 15 within the normal movement range (within the ranges of FIGS. 8B and 8C). To move up and down.
- the second control and the mounting control described above are executed by the control of the second motor 31 by the shaft controller 300.
- the axis controller 300 moves the head 15 further upward than the upper limit of the normal movement range (see FIG. 8D), and causes the dispensing tip 80 to be detached from the tip mounting portion 153A.
- the axis controller 300 is configured so that the tip mounting portion 153A of the head 15 and the proximal end portion 81 of the dispensing tip 80 are aligned in the vertical direction (see FIG. 8A).
- the head 15 is lowered by an amount necessary for fitting the mounting portion 153 ⁇ / b> A into the base end portion 81.
- the axis control unit 300 controls the movement of the head device 1 in the X direction and the Y direction by controlling the driving of the X axis motor 302 and the Y axis motor 301. For example, as shown in FIGS. 7A and 7B, when the first container C1 and the second container C2 are present, the head 15 (dispensing tip 80) is second from above the first container C1.
- the axis control unit 300 controls the X-axis motor 302 and the Y-axis motor 301 to move the head device 1 so as to move over the container C2.
- the dispensing tip 80 is moved by the movement (first control) of the piston member 14 in the vertical direction by driving the first ball screw device 10.
- the cell culture fluid liquid containing the object
- the dispensing tip 80 can be automatically detached from the tip mounting portion 153 ⁇ / b> A of the head 15 by the upward movement (second control) of the one frame 21 by driving the second ball screw device 30. Therefore, the work of sucking and discharging the cell culture solution using the dispensing tip 80 and the disposal operation of the dispensing tip 80 when the dispensing tip 80 needs to be discarded after use can be highly automated. .
- the dispensing tip 80 is removed from the head 15 by the arm member 24 including the guide recess 241 having an opening width (inner diameter) slightly larger than the outer diameter of the head 15. For this reason, the dispensing tip 80 can be detached from the tip mounting portion 153 ⁇ / b> A by a simple upward movement of the head 15 relative to the arm member 24.
- the head device 1 it is possible to replace only the replacement part 153 of the head 15 to which the dispensing tip 80 is actually mounted. Accordingly, when the tip mounting portion 153A is contaminated, the replacement portion 153 can be removed from the lower end of the rod main body portion 150 and cleaned. Further, when a dispensing tip 80 having a different diameter is attached to the head 15, if another replacement part 153 matching the diameter is attached to the rod main body 150, the diameter can be quickly changed.
- FIG. 15 is a perspective view of the moving device 4
- FIG. 16 is a perspective view of a head unit 61 in which the head device 1 is incorporated.
- the moving device 4 includes a support frame 41, a base 42 supported by the support frame 41, a cell movement line 50 assembled to the base 42, a head unit 61 and an illumination unit 62 disposed above the base 42, and An imaging unit 63 is provided below the base 42.
- the support frame 41 includes a basic frame 411 and a pair of side frames 412.
- the base frame 411 is a rectangular parallelepiped frame assembly long in the X direction, and includes a rectangular lower frame frame 411A and an upper frame frame 411B thereon.
- a guide rail 413 for moving the imaging unit 63 in the X direction is provided on the upper surface of the upper frame frame 411B.
- the base 42 is a rectangular flat plate having a predetermined rigidity, part or all of which is made of a light-transmitting material, and having substantially the same size as the base frame 411 in a top view.
- a frame mount 43 is erected on the base 42.
- the frame mount 43 includes an upper frame 431 and a middle frame 432 which are flat plates extending in the X direction.
- An upper guide rail 433 for moving the head unit 61 along the X direction is assembled on the upper surface of the upper frame 431.
- a middle guide rail 434 for moving the illumination unit 62 along the X direction is assembled on the upper surface of the middle frame 432.
- the cell movement line 50 includes elements necessary for performing a series of cell movement steps for extracting a desired cell aggregate from the cell-containing liquid and moving the cell aggregate to a predetermined container in the X direction.
- the cell migration line 50 includes an object stock unit 51 for storing a cell-containing liquid, a dispensing tip stock unit 52, a cell sorting unit 53 for sorting cell aggregates by dispensing a cell-containing liquid, a chip stock unit 54, A chip imaging unit 55, a cell transfer unit 56 that receives the selected cell aggregate, a black cover mounting unit 57, and a chip discarding unit 58 are provided.
- the container included in the object stock unit 51 is a container corresponding to the first container C1 illustrated in FIG. 7A
- the container included in the cell sorting unit 53 is illustrated in FIG. 7B. This is a container corresponding to the second container C2.
- the head unit 61 includes a unit main body 611, a head portion 612, an X slider 613, and a Y slider 614.
- the head portion 612 includes a plurality of cylinder tip heads 615 to which a plurality of cylinder tips 70 are attached, a head 15 for attaching the dispensing tips 80 described above, and a nozzle 616.
- a nozzle 616 for attaching the dispensing tips 80 described above.
- the nozzle 616 is assembled to the unit main body 611 so as to be movable up and down, and includes a suction cup 617 at the lower end.
- a mechanism for moving the head 15 in the Z direction such as the first and second ball screw devices 10 and 30 shown in FIGS. 1 to 5, and a cylinder tip head 615 in the Z direction. It has a built-in mechanism for moving it.
- the X slider 613 is assembled to the upper guide rail 433.
- An X drive motor 441 corresponding to the X-axis motor 302 in FIG. 14 is attached to the upper guide rail 433.
- the Y slider 614 supports the unit main body 611 at one end (front end) in the Y direction.
- the Y slider 614 is assembled to a Y rail (not shown in FIG. 15) disposed on the upper surface of the X slider 613.
- the Y slider 614 and the unit main body 611 move in the Y direction. That is, the head portion 612 is movable in the X direction and the Y direction as the unit main body 611 moves along the upper guide rail 433 and the Y rail. Therefore, the head unit 612 can move along the predetermined movement path on the cell movement line 50 above the base 42.
- the illumination unit 62 is movably disposed above the base 42 in order to illuminate the cell sorting unit 53 and the cell transfer unit 56 exclusively from above.
- the illumination is used as transmitted illumination when the imaging unit 63 images a cell aggregate held in the cell sorting unit 53 or the cell transfer unit 56.
- the illumination unit 62 includes an illuminator 621 that emits illumination light, an X slider 622, and a holder 623.
- the X slider 622 is assembled to the middle guide rail 434.
- An illumination unit drive motor 443 is attached to the middle guide rail 434. By the operation of the drive motor 443, the X slider 622 moves on the middle guide rail 434 in the X direction.
- the holder 623 holds the illuminator 621 and is assembled so as to be movable by a short distance in the Y direction with respect to the X slider 622 by a driving device (not shown). Accordingly, the illuminator 621 is movable in the X direction and the Y direction above the base 42.
- the imaging unit 63 is arranged movably below the base 42 in order to image the cell clumps held in the cell sorting unit 53 and the cell transfer unit 56 from below the base 42. Furthermore, in this embodiment, the imaging unit 63 is also used for observing the mounting state of the cylinder chip 70 on the head 615 in the chip imaging unit 55.
- the imaging unit 63 includes a camera 631, an epi-illuminator 632, an X slider 633, and a holder 634.
- the camera 631 includes a CCD image sensor and an optical system that forms a light image on the light receiving surface of the CCD image sensor.
- the epi-illuminator 632 is a light source used when the imaging object of the camera 631 is not a light transmission body or when it is fluorescently stained.
- the X slider 633 is assembled to the guide rail 413 of the support frame 41.
- An imaging unit drive motor 444 is attached to the guide rail 413. By the operation of the drive motor 444, the X slider 633 moves on the guide rail 413 in the X direction.
- the holder 634 holds the camera 631 and the epi-illuminator 632 and is assembled so as to be movable in the Y direction by a short distance with respect to the X slider 633 by an unillustrated driving device. Therefore, the camera 631 can move in the X direction and the Y direction below the base 42.
- FIG. 17 is a perspective view showing the components of the cell movement line 50 with the base 42 omitted.
- arrangement positions of the head unit 61, the illumination unit 62, and the imaging unit 63 are also schematically added.
- the cell movement line 50 is, in order from the upstream side in the X direction (left end side in FIG. 17), a dispensing tip stock unit 52, an object stock unit 51, a tip stock unit 54, a tip imaging unit 55, a cell sorting unit 53, and black.
- the cover mounting part 57, the cell transfer part 56, and the chip discarding part 58 are arranged in a line. The positions of these portions on the base 42 are determined by positioning members 42S.
- the arrangement of the cell movement lines 50 shown here is an example, and the arrangement position of each part can be appropriately set in consideration of work efficiency and the like.
- the black cover placement unit 57 may be disposed on the front side (+ Y) or the rear side ( ⁇ Y) of the cell sorting unit 53 and the cell transfer unit 56.
- the object stock part 51 is a part that stores a cell culture solution (liquid) in which a large amount of cell aggregates (objects) are dispersed.
- the object stock unit 51 includes a box 511 arranged at a predetermined position on the base 42, a tube 512 (first container) held by the box 511, and a lid member 513 placed on the box 511. Is provided.
- the tube 512 is a cylindrical container having an open upper surface, and stores a cell culture solution containing cell aggregates and contaminants.
- the lid member 513 is a member for closing the opening of the tube 512.
- the dispensing tip stock part 52 is a part for storing a large number of the dispensing tips 80 described above.
- the dispensing tip stock portion 52 includes a holding box 521 that holds the dispensing tips 80 arranged in a matrix in a standing state (a state in which the base end portion 81 is positioned above), and a box lid member 523. Yes. Inside the holding box 521, a holder member 522 for arranging and holding the dispensing tips 80 is disposed.
- the cell sorting unit 53 is a part for sorting a cell aggregate of a desired size from a cell culture solution containing cell aggregates and contaminants of various sizes.
- the cell sorting unit 53 includes a dish 64, a holding table 531, and a table lid member 532.
- the dish 64 is a top-opening container in which a cell culture solution containing cell aggregates is dispensed by the dispensing tip 80 and can store the cell culture solution.
- the holding table 531 positions and holds the dish 64.
- the table lid member 532 is a lid member for covering the upper surfaces of the dish 64 and the holding table 531.
- the dish 64 includes a well plate having a plurality of recesses for supporting a cell aggregate on the upper surface side.
- a through-hole is provided at the bottom of the recess, and cell aggregates to be extracted are held in the recess, and impurities and the like fall from the through-hole. Since the cell aggregates and the contaminants are thus selected, only the cell aggregates remain on the well plate.
- An image of the cell agglomerate held in the concave portion is captured by the camera 631 while the illumination unit 62 is lit. Thereby, the position of the cell aggregate to be aspirated is specified.
- the tip stock portion 54 is a portion that holds a large number of cylinder tips 70.
- the cylinder chip 70 includes a syringe having a tubular passage serving as a suction path for cell aggregates, and a plunger that moves forward and backward in the tubular passage while being in sliding contact with the inner peripheral wall of the syringe that defines the tubular passage.
- the chip head 615 can be attached and detached.
- the cylinder chip 70 functions to suck the cell aggregates carried in the recesses of the well plate described above, transport the cell aggregates with the movement of the head unit 61, and discharge the cell aggregates to the cell transfer unit 56. .
- the chip stock unit 54 includes a holding box 541 and a box lid member 543.
- the holding box 541 holds the cylinder chips 70 arranged in a matrix in an upright state.
- a holder member 542 for aligning and holding the cylinder chip 70 is arranged inside the holding box 541.
- the cylinder chip 70 is held by the holding box 541 with the upper end portion protruding upward from the upper end surface of the holding box 541.
- the box lid member 543 is a lid member that covers the upper end surface of the holding box 541 and covers the cylinder chip 70.
- the chip imaging unit 55 is a pit that provides a position where an image of the cylinder chip 70 mounted on the cylinder chip head 615 is captured.
- the imaging is performed by the imaging unit 63.
- the camera 631 of the imaging unit 63 is moved directly below the chip imaging unit 55 and captures an image of each cylinder chip 70 under illumination of the epi-illuminator 632.
- the XYZ coordinate position of the suction port 71T of the cylinder chip 70 is obtained.
- a correction value is derived from the difference between the coordinate position and a predetermined reference position. The correction value is used as a correction value when moving the head 615.
- the chip imaging unit 55 itself may be equipped with a lighting fixture such as an LED lighting fixture, and the imaging may be performed under illumination of the lighting fixture.
- the cell transfer part 56 is a part that is arranged in the vicinity of the downstream end in the X direction in the cell movement line 50 and serves as a movement destination of the cell aggregate aspirated from the dish 64 of the cell sorting part 53.
- the cell transfer unit 56 includes a microplate 65, a holding table 561, and a table lid member 562. Instead of the microplate 65, the cell transfer unit 56 may be provided with a container similar to the dish 64.
- the microplate 65 is a plate in which a large number of small wells 66 whose upper surfaces are open are arranged in a matrix.
- the microplate 65 is formed of a translucent member, for example, a transparent plastic.
- one cell aggregate is accommodated in one well 66. Therefore, the cell aggregate in the state accommodated in each well 66 can be imaged by the camera 631.
- the array pitch of the wells 66 is set to be substantially the same as the array pitch of the group of cylinder chips 70 mounted on the heads 615 arranged in a line. Thereby, it is possible to discharge the cell aggregate from the group of cylinder chips 70 to the well 66 simultaneously.
- the holding table 561 positions and holds the microplate 65.
- the table lid member 562 is a lid member for covering the upper surfaces of the microplate 65 and the holding table 561.
- the black cover placement part 57 is a part on which the first black cover 571 placed on the cell transfer part 56 and the second black cover 572 placed on the cell sorting part 53 are placed.
- the first and second black covers 571 and 572 are light-shielding bodies that are used when the cell aggregates carried on the dish 64 or the microplate 65 are imaged while being shielded from light.
- the first and second black covers 571 and 572 are covered so as to cover the holding tables 531 and 561 when a fluorescent agent is added to the cell culture solution and the cell aggregate is observed with fluorescence.
- the tip discarding portion 58 is disposed at the most downstream end portion in the X direction in the cell movement line 50, and is a portion where the used cylinder tip 70 and the dispensing tip 80 that have finished the above suction and discharge operations are discarded.
- the tip discarding unit 58 includes a collection box 581 for accommodating the used cylinder tip 70 and the dispensing tip 80.
- the head unit 61 equipped with the cylinder tip 70 or the dispensing tip 80 is moved onto the opening 582 of the collection box 581 to remove the cylinder tip 70 from the cylinder tip head 615 or the above-described dispensing.
- the removal operation of the chip 80 from the head 15 is performed. By this detaching operation, the cylinder tip 70 or the dispensing tip 80 falls to the collection box 581 through the opening 582.
- the operation of the moving device 4 configured as described above is controlled by a control unit (such as a personal computer connected to the moving device 4) corresponding to the axis control unit 300 of FIG.
- the control unit roughly causes the moving device 4 to perform a dispensing operation using the head 15 according to the present embodiment and a cell moving operation using the cylinder tip head 615.
- the control unit sequentially [Control 1] Control for moving the head unit 61 onto the dispensing tip stock portion 52 and mounting the dispensing tip 80 on the head 15.
- Control 2 Control that moves the head unit 61 onto the object stock unit 51 and sucks the cell culture solution containing the cell aggregates stored in the tube 512 into the dispensing tip 80 by a predetermined dispensing amount.
- Control 3 Control for moving the head unit 61 onto the cell sorting unit 53 and discharging the cell culture solution in the dispensing tip 80 to the dish 64
- Control 4 Control for moving the head unit 61 onto the tip discarding section 58, removing the used dispensing tip 80 from the head 15, and discarding it in the collection box 581. Is executed by the mobile device 4.
- control unit sequentially, [Control 5] Control for moving the head unit 61 onto the chip stock portion 54 and mounting the cylinder chip 70 on the cylinder chip head 615. [Control 6] Control that moves the head unit 61 onto the cell sorting unit 53 and sucks the cell aggregates stored in the dish 64 into the cylinder chip 70. [Control 7] Control for moving the head unit 61 onto the cell transfer unit 56 and discharging the cell aggregate in the cylinder chip 70 onto the microplate 65, and [Control 8] Control to move the head unit 61 onto the chip disposal unit 58, remove the used cylinder chip 70 from the cylinder chip head 615, and discard it in the collection box 581. Is executed by the mobile device 4.
- the control 1 is control for causing the operation shown in FIG. 8A to be performed, and is control described as “mounting control” in the description of the axis control unit 300 in FIG.
- the head unit 61 is moved onto the dispensing tip stock portion 52, the head 15 is aligned with respect to one dispensing tip 80, and then the head 15 is lowered by driving the second ball screw device 30.
- the tip mounting portion 153A is press-fitted into the mounting hole of the base end portion 81 of the dispensing tip 80. Thereby, the mounting of the dispensing tip 80 to the head 15 is completed.
- the control 2 and the control 3 are controls for performing the operations shown in FIGS. 7A and 7B, and are the controls described as the “first control” in the description of the axis control unit 300. is there.
- the operation of sucking the cell culture solution into the dispensing tip 80 and the operation of discharging it from the dispensing tip 80 are realized by the piston member 14 by the first ball screw device 10. This point is as detailed above.
- the control 4 is control for causing the operation shown in FIG. 8D to be performed, and is control described as “second control” in the description of the axis control unit 300.
- the control here is control for raising the head 15 from the upper limit of the normal movement range by driving the second ball screw device 30 as described above.
- the dispensing tip 80 is attached to the head 15, and the tube 512 by the dispensing tip 80 (first container C1).
- a series of operations from the suction of the cell culture solution from the above, the discharge of the cell culture solution to the dish 64 (second container C2), and the disposal of the dispensing tip 80 to the tip disposal unit 58 are performed by the control unit.
- a dispensing tip mounting head device is a head device to which a dispensing tip for sucking a liquid containing an object and discharging the sucked liquid is attached, and includes a piston member, A first shaft member that engages the piston member and moves the piston member in a vertical direction; and a cylindrical space that includes a cylinder space that movably accommodates the piston member in a vertical direction.
- a cylindrical rod having a tip mounting portion into which a base end portion is fitted at a lower end, a first frame on which the first shaft member and the cylindrical rod are mounted, and the first frame are engaged, and the first A second shaft member that moves the frame in the vertical direction and a second guide member that is mounted with the second shaft member and guides the vertical movement of the cylindrical rod accompanying the vertical movement of the first frame.
- a shaft control unit that controls the operation of the first shaft member and the second shaft member, the shaft control unit, in a state where the dispensing tip is mounted on the tip mounting unit, By moving the piston member in the vertical direction, the first control for controlling the first shaft member so that the liquid is sucked and discharged by the dispensing tip, and by moving the first frame in the upward direction, And a second control for controlling the second shaft member to cause the guide portion and the proximal end portion of the dispensing tip to interfere with each other and to disengage the dispensing tip from the tip mounting portion.
- the dispensing tip can suck and discharge the liquid containing the object by moving the piston member in the vertical direction by driving the first shaft member. Furthermore, the dispensing tip can be automatically detached from the tip mounting portion by the upward movement of one frame by driving the second shaft member. Accordingly, it is possible to highly automate the work of sucking and discharging the object using the dispensing tip, and the disposal work of the dispensing tip when it is necessary to discard it after use.
- the cylindrical rod has a cylindrical shape
- the guide portion is an arm member having a guide recess having an inner diameter slightly larger than an outer diameter of the cylindrical rod.
- the dispensing tip is detached from the tip mounting portion by the interference between the lower end surface of the arm member and the upper end edge of the proximal end portion of the dispensing tip. .
- the guide concave portion having an inner diameter slightly larger than the outer diameter of the cylindrical rod is provided, the dispensing from the tip mounting portion by simple upward movement of the cylindrical rod with respect to the guide member. The tip can be removed.
- the cylindrical rod is detachably mounted on a rod main body portion having the cylinder space and a lower end of the rod main body portion, and communicates with the cylinder space inside. It is desirable to provide a space and an exchange part having the chip mounting part on the outer peripheral surface.
- this head device it is possible to replace only the portion (exchanger) where the dispensing tip is actually mounted in the cylindrical rod. Therefore, when the tip mounting portion is contaminated, the replacement portion can be removed from the lower end of the rod body portion and cleaned. In addition, when a dispensing tip having a different diameter is mounted, if another replacement portion matching the diameter is attached to the rod main body, it is possible to quickly respond to the diameter change.
- the first shaft member includes a first screw shaft extending in a vertical direction and a first nut member engaged with the first screw shaft.
- the piston member includes an upper end provided with an engaging portion fixed to the first nut member, a lower end provided with a seal member on a peripheral surface, and between the upper end and the lower end. It is desirable to provide a middle portion having a housing space for housing the first screw shaft.
- the head device can be constructed with a simple structure by applying a ball screw structure to the first shaft member and adopting a piston member having a structure adapted thereto.
- the second shaft member includes a second screw shaft extending in the vertical direction and a second nut member engaged with the second screw shaft.
- the first frame is preferably fixed to the second nut member.
- the first frame can be moved up and down by applying a ball screw structure to the second shaft member. Therefore, the drive system by the second shaft member can be simplified.
- the second frame includes a vertical frame to which a guide rail for guiding the vertical movement of the first frame is attached, a bearing portion attached to a lower end of the vertical frame, and a lower end of the second screw shaft. And a through-hole through which the cylindrical rod passes, and a horizontal frame to which the guide portion is assembled.
- the guide rail and the guide portion can be efficiently arranged using the vertical frame and the horizontal frame.
- a moving device includes a dispensing tip mounting head device, a first container that stores an object, a second container that receives the object, and the head device that includes the first container. And a head moving mechanism for moving in a horizontal direction between the first container and the second container.
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Abstract
Description
[第1制御]ピストン部材14の上下方向への移動によって、分注チップ80による細胞凝集塊を含む細胞培養液の吸引及び吐出が行われるよう、第1ボールねじ装置10を制御する(図7A、図7B、図9~図12参照)。
[第2制御]第1フレーム21の上方向への移動によって、アーム部材24(ガイド部)と分注チップ80の基端部81とを干渉させ、チップ装着部153Aから分注チップ80を離脱させるよう、第2ボールねじ装置30を制御する(図8A~8D、図13参照)。
[制御1]ヘッドユニット61を分注チップストック部52上に移動させ、ヘッド15に分注チップ80を装着させる制御、
[制御2]ヘッドユニット61を対象物ストック部51上に移動させ、チューブ512に貯留された、細胞凝集塊を含む細胞培養液を所定の分注量だけ分注チップ80内に吸引させる制御、
[制御3]ヘッドユニット61を細胞選別部53上に移動させ、分注チップ80内の前記細胞培養液をディッシュ64に吐出させる制御、及び、
[制御4]ヘッドユニット61をチップ廃棄部58上に移動させ、使用済みの分注チップ80をヘッド15から取り外し、回収ボックス581内に廃棄させる制御、
を移動装置4に実行させる。
[制御5]ヘッドユニット61をチップストック部54上に移動させ、シリンダチップヘッド615にシリンダチップ70を装着させる制御、
[制御6]ヘッドユニット61を細胞選別部53上に移動させ、ディッシュ64に貯留された細胞凝集塊をシリンダチップ70内に吸引させる制御、
[制御7]ヘッドユニット61を細胞移載部56上に移動させ、シリンダチップ70内の細胞凝集塊をマイクロプレート65に吐出させる制御、及び、
[制御8]ヘッドユニット61をチップ廃棄部58上に移動させ、使用済みのシリンダチップ70をシリンダチップヘッド615から取り外し、回収ボックス581内に廃棄させる制御、
を移動装置4に実行させる。
Claims (7)
- 対象物を含む液体の吸引、及び前記吸引した液体の吐出を行う分注チップが装着されるヘッド装置であって、
ピストン部材と、
前記ピストン部材が係合され、該ピストン部材を上下方向に移動させる第1軸部材と、
前記ピストン部材を上下方向に移動可能に収容するシリンダ空間を含む筒状空間を備え、前記分注チップの基端部が嵌め込まれるチップ装着部を下端に備えた筒状ロッドと、
前記第1軸部材及び前記筒状ロッドが搭載される第1フレームと、
前記第1フレームが係合され、該第1フレームを上下方向に移動させる第2軸部材と、
前記第2軸部材が搭載され、前記第1フレームの上下方向の移動に伴う前記筒状ロッドの上下方向の移動をガイドするガイド部を備える第2フレームと、
前記第1軸部材及び前記第2軸部材の動作を制御する軸制御部と、を備え、
前記軸制御部は、
前記分注チップが前記チップ装着部に装着された状態において、
ピストン部材の上下方向への移動によって、前記分注チップによる前記液体の吸引及び吐出が行われるよう前記第1軸部材を制御する第1制御と、
前記第1フレームの上方向への移動によって、前記ガイド部と前記分注チップの基端部とを干渉させ、前記チップ装着部から前記分注チップを離脱させるよう前記第2軸部材を制御する第2制御と、を実行する分注チップ装着用ヘッド装置。 - 請求項1に記載の分注チップ装着用ヘッド装置において、
前記筒状ロッドは、円筒形状を備え、
前記ガイド部は、前記筒状ロッドの外径よりも僅かに大きい内径を有するガイド凹部を備えたアーム部材であり、
前記第2制御の際、前記アーム部材の下端面と前記分注チップの基端部の上端縁とが干渉することで、前記チップ装着部から前記分注チップが離脱される、分注チップ装着用ヘッド装置。 - 請求項1又は2に記載の分注チップ装着用ヘッド装置において、
前記筒状ロッドは、
前記シリンダ空間を備えるロッド本体部と、
前記ロッド本体部の下端に着脱可能に装着され、内部に前記シリンダ空間に連通する筒状空間を備えると共に、外周面に前記チップ装着部を備えた交換部と、
を具備する、分注チップ装着用ヘッド装置。 - 請求項1~3のいずれか1項に記載の分注チップ装着用ヘッド装置において、
前記第1軸部材は、上下方向に延びる第1ねじ軸と、該第1ねじ軸に係合される第1ナット部材とを含む第1ボールねじ装置であり、
前記ピストン部材は、
前記第1ナット部材に固定される係合部を備えた上端部と、
周面にシール部材を備えた下端部と、
前記上端部と前記下端部との間の部分であって、前記第1ねじ軸を収容する収容空間を内部に備えた中間部と、
を具備する、分注チップ装着用ヘッド装置。 - 請求項1~4のいずれか1項に記載の分注チップ装着用ヘッド装置において、
前記第2軸部材は、上下方向に延びる第2ねじ軸と、該第2ねじ軸に係合される第2ナット部材とを含む第2ボールねじ装置であって、
前記第1フレームは、前記第2ナット部材に固定されている、分注チップ装着用ヘッド装置。 - 請求項5に記載の分注チップ装着用ヘッド装置において、
前記第2フレームは、
前記第1フレームの上下方向の移動をガイドするガイドレールが取り付けられる縦フレームと、
前記縦フレームの下端に取り付けられ、前記第2ねじ軸の下端の軸受け部と、前記筒状ロッドを貫通させる貫通孔とを備え、前記ガイド部が組み付けられる横フレームと、
を備える、分注チップ装着用ヘッド装置。 - 請求項1~6のいずれか1項に記載の分注チップ装着用ヘッド装置と、
対象物を貯留する第1容器と、
対象物を受け入れる第2容器と、
前記ヘッド装置を前記第1容器と前記第2容器との間において水平方向に移動させるヘッド移動機構と、を備える移動装置。
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EP14895175.9A EP3159397B1 (en) | 2014-06-17 | 2014-06-17 | Head device for mounting dispensing tip thereon, and movement device using same |
JP2016528679A JP6293887B2 (ja) | 2014-06-17 | 2014-06-17 | 分注チップ装着用ヘッド装置及びこれを用いた移動装置 |
PCT/JP2014/065970 WO2015193958A1 (ja) | 2014-06-17 | 2014-06-17 | 分注チップ装着用ヘッド装置及びこれを用いた移動装置 |
US15/318,929 US10429403B2 (en) | 2014-06-17 | 2014-06-17 | Head device for mounting dispensing tip thereon, and movement device using same |
CN201480079598.6A CN106459866B (zh) | 2014-06-17 | 2014-06-17 | 分注尖头安装头装置以及使用该头装置的移动装置 |
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JP6293887B2 (ja) | 2018-03-14 |
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EP3159397B1 (en) | 2018-05-02 |
JPWO2015193958A1 (ja) | 2017-04-20 |
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