WO2017056142A1 - 流路モジュール及びそれを用いた細胞培養装置 - Google Patents
流路モジュール及びそれを用いた細胞培養装置 Download PDFInfo
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- WO2017056142A1 WO2017056142A1 PCT/JP2015/077236 JP2015077236W WO2017056142A1 WO 2017056142 A1 WO2017056142 A1 WO 2017056142A1 JP 2015077236 W JP2015077236 W JP 2015077236W WO 2017056142 A1 WO2017056142 A1 WO 2017056142A1
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- Prior art keywords
- branch
- flow path
- channel
- communication state
- pressing
- Prior art date
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- 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
- C12M23/00—Constructional details, e.g. recesses, hinges
- C12M23/40—Manifolds; Distribution pieces
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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
- B01F23/00—Mixing according to the phases to be mixed, e.g. dispersing or emulsifying
- B01F23/40—Mixing liquids with liquids; Emulsifying
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F25/00—Flow mixers; Mixers for falling materials, e.g. solid particles
- B01F25/50—Circulation mixers, e.g. wherein at least part of the mixture is discharged from and reintroduced into a receptacle
- B01F25/51—Circulation mixers, e.g. wherein at least part of the mixture is discharged from and reintroduced into a receptacle in which the mixture is circulated through a set of tubes, e.g. with gradual introduction of a component into the circulating flow
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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
- B01F35/00—Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
- B01F35/71—Feed mechanisms
- B01F35/717—Feed mechanisms characterised by the means for feeding the components to the mixer
- B01F35/7176—Feed mechanisms characterised by the means for feeding the components to the mixer using pumps
- B01F35/717611—Peristaltic pumps
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B81—MICROSTRUCTURAL TECHNOLOGY
- B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
- B81B3/00—Devices comprising flexible or deformable elements, e.g. comprising elastic tongues or membranes
- B81B3/0097—Devices comprising flexible or deformable elements not provided for in groups B81B3/0002 - B81B3/0094
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- 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
- C12M1/007—Flexible bags or containers
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- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
- F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
- F16K11/00—Multiple-way valves, e.g. mixing valves; Pipe fittings incorporating such valves
- F16K11/02—Multiple-way valves, e.g. mixing valves; Pipe fittings incorporating such valves with all movable sealing faces moving as one unit
- F16K11/022—Multiple-way valves, e.g. mixing valves; Pipe fittings incorporating such valves with all movable sealing faces moving as one unit comprising a deformable member
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- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
- F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
- F16K7/00—Diaphragm valves or cut-off apparatus, e.g. with a member deformed, but not moved bodily, to close the passage ; Pinch valves
- F16K7/02—Diaphragm valves or cut-off apparatus, e.g. with a member deformed, but not moved bodily, to close the passage ; Pinch valves with tubular diaphragm
- F16K7/04—Diaphragm valves or cut-off apparatus, e.g. with a member deformed, but not moved bodily, to close the passage ; Pinch valves with tubular diaphragm constrictable by external radial force
- F16K7/06—Diaphragm valves or cut-off apparatus, e.g. with a member deformed, but not moved bodily, to close the passage ; Pinch valves with tubular diaphragm constrictable by external radial force by means of a screw-spindle, cam, or other mechanical means
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- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
- F04B—POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
- F04B45/00—Pumps or pumping installations having flexible working members and specially adapted for elastic fluids
- F04B45/06—Pumps or pumping installations having flexible working members and specially adapted for elastic fluids having tubular flexible members
Definitions
- the present invention relates to a flow path switching technique in an analysis apparatus or a cell culture apparatus, and in particular, a flow path module having a plurality of branch flow paths communicating with each other and capable of communicating between desired branch flow paths and the same.
- the present invention relates to the cell culture apparatus used.
- Patent Document 1 is known as a method of culturing while circulating a culture solution in a circulation channel.
- Patent Document 1 discloses an apparatus for proliferating microorganisms while circulating a microorganism suspension in a culture medium in a circulation channel, and the culture apparatus includes a suspension outlet connected to the circulation channel, A medium supply tank connected to the circulation channel and a test channel (sampling channel) branched from the circulation channel and through which a certain amount of microorganism suspension flows.
- Patent Document 2 discloses a dialysis treatment apparatus, which has an arterial blood circuit that can be connected via a four-way valve to a blood introduction port of a die analyzer that has a plurality of hollow fiber membranes and purifies blood, and A configuration having an arterial drip chamber is disclosed.
- the blood pump is rotated forward, the arterial blood circuit, the arterial drip chamber, and the blood introduction port are communicated in this order by the four-way valve, and the patient's blood is sent to the die analyzer. Introduce.
- the blood pump when the blood pump is reversed, a configuration is described in which a blood introduction port, an arterial drip chamber, and an arterial blood circuit are communicated in this order by a four-way valve, and dialysate is returned to the patient's artery.
- the four-way valve is configured with a bag body made of a flexible member and a clamp member, and the direction of the clamp member that clamps the bag body according to the normal rotation and reverse rotation of the blood pump is determined.
- a configuration for switching is also disclosed.
- valves are provided in a flow path that connects the suspension outlet and the circulation flow path, a flow path that connects the culture medium supply tank and the circulation flow path, and a test flow path, which are different from each other.
- the suspension is discharged, the medium is supplied to the circulation channel, and the suspension is passed through the test channel. Therefore, it is not possible to reduce the number of parts or downsize the apparatus.
- no consideration is given to how the microbial suspension in the culture medium is filled in the circulation channel (hereinafter referred to as “liquid replacement”), and bubbles may be mixed into the microbial suspension. .
- a four-way valve must be rotated and two flow paths in a four-way valve must be positioned correctly.
- a four-way valve is configured with a bag made of a clamp member and a flexible member, it is essential to change the direction of the clamp member in addition to the opening and closing operation of the clamp member. It becomes difficult to realize.
- an object of the present invention is to provide a flow channel module and a cell culture apparatus using the same, which can realize complete liquid replacement of the circulation flow channel with a simple structure.
- the flow channel module of the present invention includes a first branch flow channel connected to the end of the fluid inflow channel and a second branch flow connected to the end of the outflow channel.
- Each branch channel including a channel, a third branch channel connected to the inlet end of the circulation channel, and a fourth branch channel connected to the outlet end of the circulation channel.
- a flexible branching section that allows communication between them, and an opening / closing member that closes or opens a desired branch flow path among the plurality of branch flow paths, and moves the opening / closing member in one direction to move the desired branch
- a first communication state in which the third branch channel and the fourth branch channel communicate with each other by pressing and closing the channel, and the first branch channel and the third branch channel
- a communication state switching unit that switches a second communication state in which the second branch flow path and the fourth branch flow path communicate with each other.
- the cell culture device of the present invention includes an inflow channel through which a cell suspension or a medium flows, a circulation channel through which the cell suspension or medium is circulated, a pump installed in the circulation channel, A culture vessel installed in the circulation channel downstream of the pump, a recovery bag connected to the outflow channel, a flow connected to the inflow channel, the circulation channel, and the outflow channel A channel module, wherein the channel module includes a first branch channel connected to an end of the inflow channel, a second branch channel connected to an end of the outflow channel, A third branch channel connected to the inlet side end of the circulation channel and a fourth branch channel connected to the outlet side end of the circulation channel; A flexible branch portion that allows communication, and an open / close member that closes or opens a desired branch flow path among the plurality of branch flow paths; A first communication state in which the third branch channel and the fourth branch channel communicate with each other by moving the opening and closing member in one direction and pressing and closing the desired branch channel; and A communication state switching unit configured to switch a second communication state in which the
- the present invention it is possible to provide a channel module capable of realizing complete liquid replacement of the circulation channel with a simple structure and a cell culture apparatus using the same.
- FIG. 6 is an overall schematic configuration diagram including a flow channel module having the communication state switching unit shown in FIG. 5.
- FIG. 1 It is a whole schematic block diagram containing the flow path module which has a communication state switching part shown in FIG.
- It is a schematic block diagram of the flow-path module of Example 2 which concerns on the other Example of this invention, Comprising: It is a figure which shows a 2nd communication state.
- It is a schematic block diagram of the flow-path module of Example 2 Comprising: It is a figure which shows a 1st communication state.
- a branch member described later having a plurality of branch channels communicating with each other may be referred to as a flexible branch portion.
- the pinch member that moves in one direction may be referred to as a pressing member, and the desired branch flow path in the flexible branch portion is in communication with the pressing member and a support member that maintains a stationary state.
- This mechanism is referred to as a communication state switching unit.
- the pinch member (pressing member) and the support member may be referred to as an opening / closing member.
- “liquid replacement” refers to filling a circulation channel, which will be described later, with, for example, a liquid such as a cell culture solution while preventing air bubbles from entering, or a different type of liquid to the circulation channel. It also includes the operation of switching within. Embodiments of the present invention will be described below with reference to the drawings.
- FIG. 1 is an overall schematic configuration diagram including a flow channel module according to an embodiment of the present invention
- FIG. 2 is an enlarged view of a branching member (flexible branching portion) shown in FIG.
- the flow channel module 1 of the present embodiment includes a branch member (flexible branch portion) 2 and a communication state switching portion 3.
- the branch member (flexible branch portion) 2 includes four branch passages communicating with each other, that is, the first branch passage 2 a connected to the end of the inflow passage 4 and the end of the outflow passage 5.
- the third branch flow path 2c Connected to the second branch flow path 2b connected to the section, the third branch flow path 2c connected to the inlet side end 6a of the circulation path 6, and the outlet side end 6b of the circulation path 6.
- a fourth branch flow path 2d is an overall schematic configuration diagram including a flow channel module according to an embodiment of the present invention
- FIG. 2 is an enlarged view of a branching member (flexible branching portion) shown in FIG.
- two adjacent branch channels out of the first branch channel 2 a to the fourth branch channel 2 d constituting the branch member 2 are arranged so as to be orthogonal in the horizontal plane.
- the first branch channel 2a connected to the inflow channel 4 and the fourth branch channel 2d connected to the outlet end 6b of the circulation channel 6 communicate with each other while facing each other.
- the second branch channel 2b connected to the outflow channel 5 and the third branch channel 2c connected to the inlet side end 6a of the circulation channel 6 communicate with each other while facing each other.
- the branch member (flexible branch portion) 2 is formed of a flexible film (flexible sheet), and is arranged between a pinch member 3a and a support member 3b constituting a communication state switching portion 3 to be described in detail later.
- the communication state switching unit 3 includes a pinch member (pressing member) 3a that moves in one direction and a support member 3b that maintains a stationary state, and is arranged so as to sandwich the first branch channel 2a and the second branch channel 2b.
- a pair of pinch members 3a and support members 3b are arranged.
- the branch member 2 extends over the corner where the first branch channel 2a and the second branch channel 2b are joined and the corner where the third branch channel 2c and the fourth branch channel 2d are joined.
- Another pair of pinch members 3a and support members 3b are arranged in a diagonal line in plan view that passes through the center of the.
- the crushing (pinch) of the branching member 2 shown in FIG. 1 in the 3 (i) direction that is, the pushing of the branching member 2 by the pair of pinch members 3a and the supporting member 3b arranged in a diagonal line in the above plan view. Crushing is possible.
- the branch member 2 is crushed (pinched) in the 3 (ii) direction, that is, a pair of pinch members 3a arranged so as to sandwich the first branch flow path 2a and the second branch flow path 2b described above.
- the branch member 2 can be crushed by the support member 3b.
- this communication state is referred to as a “first communication state”.
- the crushing (pinch) of the branch member 2 in the 3 (ii) direction is performed.
- the branch member 2 is crushed (pinch) in the 3 (ii) direction so as to sandwich the first branch channel 2a and the second branch channel 2b.
- the circulation channel 6 is provided with a pump 7.
- the pump 7 for example, an ironing pump that squeezes and feeds an elastic tube is used.
- the circulation flow path 6 is made of an elastic member such as a silicon tube.
- the branching member (flexible branching portion) 2 is formed by combining two flexible membranes (flexible sheets) and communicating with each other inside the first branch channel 2 a and the second Branch flow path 2b, third branch flow path 2c, and fourth branch flow path 2d.
- the outer side portions of these branch flow paths are joined at a joint 2e, and the cross section of each branch flow path is formed in a circular or elliptical shape.
- the cross section of each branch flow path is not limited to a circle or an ellipse, but may be a rectangle or a polygon. In this case, it is desirable to have a shape with rounded corners.
- the joining part 2e for example, ultrasonic welding or adhesion is used.
- the inflow channel 4, the outflow channel 5, the inlet side end 6 a of the circulation channel 6, and the outlet side end 6 b of the circulation channel 6 are preliminarily formed into the branch member (flexible branch part) 2.
- An example of joining is shown. Instead of this, it is also possible to connect each branch flow path constituting the branch member 2 to the above-described inflow flow path 4 and the like via connecting parts.
- FIG. 3 is a view for explaining a method of forming the branch member (flexible branch portion) 2.
- the second flexible sheet 11b is aligned on the first flexible sheet 11a, and then the joint portions 2e are formed at the four corners by, for example, ultrasonic welding or heat welding.
- the first branch channel 2a, the second branch channel 2b, the third branch channel 2c, and the fourth branch channel which are four branch channels defined by the joint 2e.
- a branch channel 2d is formed.
- the present invention is not limited to this, for example, as shown in the left diagram of FIG. 3, even when a joint 2 e made of different members is joined so as to cover the outer sides of the four branch flow channels communicating with each other. good.
- the branch member (flexible branch portion) 2 is placed between the pinch member (pressing member) 3a and the support member 3b constituting the communication state switching portion 3. Workability at the time of installation or mounting is improved.
- the branch member which does not have the junction part 2e which consists of a dissimilar member (flexibility A configuration using the branching portion 2 may be adopted.
- the branch member (flexible branch portion) 2 is not necessarily formed by the two flexible sheets 11a and 11b, and one flexible sheet (flexible film) is folded and formed. Also good.
- FIG. 4 is a schematic configuration diagram of the communication state switching unit 3.
- the communication state switching unit 3 includes a pinch member (pressing member) 3a that moves in one direction, a support member 3b that is stationary, and a movable iron core 3c that is fixed to one end of the pinch member 3a.
- the one end of the spring 3e, the coil 3f, and the support member 3b whose one end is connected to the lower surface of the movable core 3c and the other end is connected to the fixed core 3g is fixed, and the movable core 3c, the spring 3e, and the coil 3f are fixed.
- a housing 3d is provided.
- the pinch member 3a that functions as a pressing member moves in one direction along with the operation of the movable iron core 3c.
- the pinch member 3a and the movable iron core 3c are collectively referred to as an actuator hereinafter.
- One end of the support member 3b is fixed to the upper surface of the housing 3d, and always remains stationary.
- the support member 3b includes a standing portion that stands vertically upward from the upper surface of the housing 3d, a normally closed side member (NC side member) 3b1 that is bent at the upper end of the standing portion and extends in the horizontal direction, and It is comprised from the normally open side member (NO side member) 3b2 which is located below the NC side member 3b1 at a predetermined interval and extends in the horizontal direction from the standing portion.
- the pinch member 3a and the support member 3b only need to have rigidity, and are formed of, for example, stainless steel, iron, or resin.
- the branch member (flexible branch portion) 2 is inserted and installed between the support member 3b and the pinch member 3a.
- FIG. 4 for convenience of explanation, the shapes of the pinch member 3a and the support member 3b are simplified.
- the actuator moves up and down in FIG. 4 by the spring force generated by the spring 3e and the magnetic force generated by energizing the coil 3f. That is, the actuator moves in one direction.
- the actuator is biased by the spring force of the spring 3e and pushed up toward the NC side member 3b1 constituting the support member 3b.
- the branch flow path of the branch member (flexible branch part) 2 installed between the NC side member 3b1 and the pinch member 3a is crushed (pinched).
- the coil 3f when the coil 3f is energized, the actuator is drawn toward the fixed iron core 3g against the spring force of the spring e.
- the branch flow path of the branch member (flexible branch part) 2 installed between the NO side member 3b2 and the pinch member 3a is crushed (pinched).
- a drive source of an actuator it is good also as a structure using mechanical force like pressures, such as air pressure or a hydraulic pressure, or a cam other than the structure using an electromagnetic force like this figure.
- FIG. 5 is a diagram showing an example of the pinch member (pressing member) constituting the communication state switching unit and the shape of the support member and the mutual arrangement relationship.
- the pinch member (pressing member) 3a1 and the support member 3b'1 constitute an opening / closing member.
- the state shown in FIG. 5 shows a case where the above-described coil 3f is in a non-energized state. As shown in FIG.
- the support member 3b ′ is positioned below the NC side member 3b1 that is bent at the upper end of the standing portion and extends in the horizontal direction at a predetermined interval from the NC side member 3b1. It has NO side member 3b2 'extended
- These NC side member 3b1 and NO side member 3b2' are distribute
- the pinch member (pressing member) 3a1 is a standing portion that stands vertically upward, and a first pressing portion 3a11 that is positioned at the upper end of the standing portion and extends in the horizontal direction so as to face the NC side member 3b1.
- the second pressing portion 3a12 that is arranged on one end side of the first pressing portion 3a11 and extends in the horizontal direction so as to face the NO-side member 3b2 ′, and one end of the first pressing portion 3a11 in the same manner as the second pressing portion 3a12
- the third pressing portion 3a13 is provided on the side and extends in the horizontal direction so as to face the NO-side member 3b2 ′.
- the 2nd press part 3a12 and the 3rd press part 3a13 are distribute
- the end of 3a13 on the first pressing portion 3a11 side is positioned so that the respective extension lines are connected. Further, the end on the first pressing portion 3a11 side of the second pressing portion 3a12 and the end on the first pressing portion 3a11 side of the third pressing portion 3a13 are open to the one end portion of the first pressing portion 3a11 with a predetermined opening. It is connected with a V-shaped part with a corner. Thus, the second pressing portion 3a12 and the third pressing portion 3a13 do not interfere with or come into contact with the standing portion of the support member 3b '.
- the gap ⁇ G between the second pressing portion 3a12 constituting the pinch member (pressing member) 3a1 and the NO-side member 3b2 ′ constituting the support member 3b ′, and the third pressing portion may be equal to or larger than the outer diameter of each branch flow path (2a, 2b, 2c, 2d) provided in the branch member (flexible branch portion) 2, It is desirable to make it approximately equal to the outer diameter of the branch flow path.
- the branch portion (flexible branch portion) to the communication state switching portion 3 ) 2 is installed as follows, for example.
- a branch member between the second pressing portion 3a12 constituting the pinch member (pressing member) 3a1 and the NO side member 3b2 ′ constituting the support member 3b ′
- the first branch flow path 2a of the flexible branch portion 2 is inserted, and the second branch flow path 2b is inserted between the third pressing portion 3a13 and the NO-side member 3b2 ′.
- the coil 3f is energized, the pinch member (pressing member) 3a1 is moved downward, and the first branch passage 2a is crushed (pinched) by the second pressing portion 3a12 and the NO-side member 3b2 ′.
- the second branch flow path 2b is crushed by the 3 pressing portion 3a13 and the NO side member 3b2 ′.
- a gap ⁇ G is formed between the NC side member 3b1 constituting the support member 3b ′ and the first pressing portion 3a11 constituting the pinch member (pressing member) 3a1.
- the third branch channel 2c and the fourth branch channel 2d are inserted between the NC-side member 3b1 and the first pressing portion 3a11.
- the lower surface of the corner where the third branch flow path 2c and the fourth branch flow path 2d are joined is on the first pressing portion 3a11, and the third branch flow path 2c and the fourth branch flow It arrange
- route 2d joins may be located just under NC side member 3b1.
- the lower surface of the corner where the first branch flow path 2a and the second branch flow path 2b are joined is on the first pressing portion 3a11, and the first branch flow path 2a and the second branch flow It arrange
- Fig. 6 shows another example of the shape of the pinch member (pressing member) and the supporting member constituting the communication state switching unit and the mutual arrangement relationship.
- the support member 3b "has a predetermined distance from the NC side member 3b11 and the NC side member 3b11, which join the upper ends of the two standing portions standing in the vertical direction.
- the first NO-side member 3b21 having one end coupled to one standing portion and extending in the horizontal direction from the standing portion, and one end coupled to the other standing portion and the standing portion It has the 2nd NO side member 3b22 extended
- the 1st NO side member 3b21 and the 2nd NO side member 3b22 are located in the same horizontal surface, and the direction where each extends is a reverse direction. Further, the first NO side member 3b21 and the second NO side member 3b22 are arranged so as to be orthogonal to the NC side member 3b11 in the vertical projection plane.
- the pinch member (pressing member) 3a2 is formed at the upper end portion of the standing portion erected in the vertical direction, with the first pressing portion 3a21 and the first pressing portion 3a21 extending in the horizontal direction centering on the upper end portion of the erected portion.
- a second pressing portion 3a22 that is arranged on one end side and extends in the horizontal direction so as to face the first NO side member 3b21, and is arranged on the other end side of the first pressing portion 3a21 and faces the second NO side member 3b22.
- a third pressing portion 3a23 extending in the horizontal direction is provided. The end of the second pressing portion 3a22 on the first pressing portion 3a21 side and the end of the first pressing portion 3a21 are connected by an arcuate portion.
- the edge part by the side of the 1st press part 3a21 of the 3rd press part 3a23 and the edge part of the 1st press part 3a21 are connected by the circular-arc-shaped part. Accordingly, the standing portion of the support member 3b ′′ to which the first NO-side member 3b21 is connected does not interfere with or come into contact with the second pressing portion 3a22. Similarly, the second NO-side member 3b22 is connected. The standing portion of the supporting member 3b ′′ and the third pressing portion 3a23 do not interfere with or come into contact with each other. In addition, as shown in FIG. 6, the 2nd press part 3a22 and the 3rd press part 3a23 are extended in a mutually reverse direction.
- the gap ⁇ G between the second pressing portion 3a22 constituting the pinch member (pressing member) 3a2 and the first NO-side member 3b21 constituting the support member 3b ′′, and the third pressing portion is equal to or larger than the outer diameter of each branch flow path (2a, 2b, 2c, 2d) provided in the branch member (flexible branch portion) 2. It is desirable that it is almost equal to the outer diameter of the branch channel.
- the gap ⁇ G shown in FIG. 6 is substantially the same as the outer diameter of the branch flow path provided in the branch member (flexible branch portion) 2, the branch portion to the communication state switching portion 3 (flexible branch portion) ) 2 will be described below.
- the four branch flow paths provided in the branch member (flexible branch section) 2 communicate with each other while the first branch flow path 2a and the second branch flow path 2b face each other. It is assumed that the third branch flow path 2c and the fourth branch flow path 2d are arranged to communicate with each other while facing each other. In a state in which the coil 3f shown in FIG. 4 is not energized, a branch is made between the second pressing portion 3a22 constituting the pinch member (pressing member) 3a2 and the first NO-side member 3b21 constituting the support member 3b ′′.
- the 1st branch flow path 2a is inserted between the 3rd press part 3a23 and the 2nd NO side member 3b22. Thereafter, the coil 3f is energized, the pinch member (pressing member) 3a2 is moved downward, and the second branch passage 2b is crushed (pinched) by the second pressing portion 3a22 and the first NO-side member 3b21. The first branch passage 2a is crushed by the third pressing portion 3a23 and the second NO side member 3b22. Thereby, the NC side member 3b11 and the pinch member (pressing member) 3a2 constituting the support member 3b ′′ are With the first pressing portion 3a21 to be configured Gap ⁇ G is formed.
- the third branch channel 2c and the fourth branch channel 2d are inserted between the NC-side member 3b11 and the first pressing portion 3a21.
- the lower surface of the corner where the third branch flow path 2c and the fourth branch flow path 2d are joined is on the first pressing portion 3a21, and the third branch flow path 2c and the fourth branch flow It arrange
- route 2d joins may be located just under NC side member 3b11.
- the lower surface of the corner where the first branch flow path 2a and the second branch flow path 2b join is on the first pressing part 3a21, and the first branch flow path 2a and the second branch flow It arrange
- route 2b joins may be located just under NC side member 3b11.
- the configuration of the open / close member shown in FIG. 6, ie, the pinch member 3a2 and the support member 3b ′′, is more pinch than the configuration of the open / close member shown in FIG. 5, ie, the pinch member (pressing member) 3a1 and the support member 3b ′.
- There is little generation of bending force on the member but there is no problem in particular using either the configuration of the opening / closing member shown in Fig. 5 or the configuration of the opening / closing member shown in Fig. 6.
- the opening / closing member shown in Fig. 5 and Fig. 6 Which one of the opening and closing members is used may be determined depending on the usage of the branching member and the arrangement of the components, etc.
- the height direction of the NC side member 3b1 and the NO side member 3b2 ′ in FIG. it is necessary to change the shape so that the NC side member 3b1 and the standing portion of the pinch member (pressing member) 3a1 do not interfere with or come into contact with each other.
- a portion corresponding to the standing portion of the pinch member (pressing member) 3a1 is an arcuate portion, etc.
- the flow channel module 1 includes a branch member (flexible branch portion) 2 and a communication state switching portion 3 shown in FIG.
- the branch member (flexible branch portion) 2 includes a first branch channel 2a connected to the end of the inflow channel 4, a second branch channel 2b connected to the end of the outflow channel 5, A third branch channel 2c connected to the inlet side end 6a of the circulation channel 6 and a fourth branch channel 2d connected to the outlet side end 6b of the circulation channel 6 are provided.
- the first branch flow path 2a and the fourth branch flow path 2d communicate with each other while facing each other, and the second branch flow path 2b and the third branch flow path 2c communicate with each other while facing each other.
- the third branch channel 2c connected to the inlet end 6a of the circulation channel 6 and the fourth branch channel 2d connected to the outlet end 6b of the circulation channel 6 are arranged adjacent to each other. Is done.
- the branch member (flexible branch portion) 2 is crushed (pinched) in the 3 (i) direction by turning off the coil 3f constituting the communication state switching portion 3 shown in FIG. That is, the first branching is performed at the first pressing portion 3a11 constituting the pinch member (pressing member) 3a1 and the NC side member 3b1 (not shown in FIG. 7) constituting the support member 3b ′ shown in FIG.
- the inflow end 4a of the inflow passage 4 and the circulation passage 6 communicates (conducts) via the first branch passage 2a and the third branch passage 2c, and the circulation passage 6
- the outlet end 6b and the outflow channel 5 are communicated (conducted) via the fourth branch channel 2d and the second branch channel 2b to form an open channel (open system), and the second communication state It becomes.
- the pump 7 installed in the circulation channel 6 is driven.
- the inside of the branch member (flexible branch portion) 2 becomes negative pressure, and a liquid such as a culture solution is sucked into the first branch channel 2 a from the inflow channel 4.
- the liquid sucked into the first branch flow path 2a is introduced into the inlet end portion 6a of the circulation flow path 6 through the third branch flow path 2c and flows through the circulation flow path 6, and the circulation flow path 6 flows into the fourth branch flow path 2d from the outlet end 6b. Thereafter, the fluid flows through the fourth branch channel 2 d and the second branch channel 2 b to the outflow channel 5.
- each branch channel first branch channel 2 a to fourth branch channel 2 d
- the gas phase bubbles is discharged from the outflow channel 5 and bubbles are attached to the inner wall by allowing the liquid to flow through the inner walls in the first branch channel 2a to the fourth branch channel 2d. Are also discharged.
- the coil 3f shown in FIG. 4 is energized to pinch the branch member (flexible branch portion) 2 in the 3 (ii) direction. That is, while pinching the 1st branch flow path 2a in 2nd press part 3a12 and NO side member 3b2 '(not shown in FIG. 7) which comprise the pinch member (pressing member) 3a1 shown in FIG.
- the second branch passage 2b is pinched by the third pressing portion 3a13 and the NO side member 3b2 ′.
- the inlet side end 6a of the circulation channel 6 and the outlet side end 6b of the circulation channel 6 are communicated (conducted) via the third branch channel 2c and the fourth branch channel 2d, thereby circulating the flow.
- a path (closed system) is formed, and the first communication state is established.
- complete fluid replacement in the circulation flow path 6 can be realized by driving the pump 7 to the second communication state by the communication state switching unit 3 and switching to the first communication state after a predetermined time has elapsed. .
- the first liquid flowing through the circulation flow path 6 in the first communication state is switched to the second communication state by the communication state switching unit 3, and the branch member (possible The flexible branch portion) 2 is discharged from the outflow channel 5 via the fourth branch channel 2d and the second branch channel 2b.
- the inflow passage 4 the first branch passage 2a, the third branch passage 2c, the circulation passage 6, Water is discharged through the four branch flow paths 2d, the second branch flow path, and the outflow flow path 5 in this order.
- liquid replacement which is a replacement operation of different types of liquids, can be realized.
- FIG. 8 is an overall schematic configuration diagram including a flow path module having the communication state switching unit shown in FIG.
- the flow path module 1 includes a branch member (flexible branch portion) 2 and a communication state switching portion 3 shown in FIG. Strictly speaking, the pinch member (pressing member) 3a2 constituting the opening / closing member shown in FIG. 6 has a second pressing part 3a22 and a third pressing part 3a23 which are not perpendicular to the first pressing part 3a21, A shape connected to the first pressing portion 3a21 at an angle (acute angle) is provided.
- the support member 3b ′′ constituting the opening / closing member is configured so that the first NO side member 3b21 and the second NO side member 3b22 are at a predetermined angle (acute angle) without being orthogonal to the NC side member 3b11.
- the branch member (flexible branch portion) 2 includes a first branch channel 2a and a second branch channel (flexible branch portion) 2 as shown in FIG.
- the third branch flow path 2c and the fourth branch flow path 2d communicate with each other while facing each other, in other words, the inlet end 6a of the circulation flow path 6.
- the outlet end 6b of the circulation channel 6 are arranged to face each other.
- the branching member (flexible branching part) 2 is crushed (pinched) in the 3 (i) direction by turning off the coil 3f constituting the communication state switching part 3 shown in FIG. That is, the second branch flow path 2b and the third branch channel 3b11 (not shown in FIG. 8) are constituted by the first pressing portion 3a21 constituting the pinch member (pressing member) 3a2 and the NC side member 3b11 (not shown in FIG. 8) constituting the support member 3b ′′.
- Branching member (flexible branching portion) in a diagonal shape in plan view so as to cross the corner where the branching flow channel 2c joins and the corner where the first branching flow channel 2a and the fourth branching flow channel 2d join. ) Pinch 2.
- the inlet end 6a of the inflow channel 4 and the circulation channel 6 communicates (conducts) via the first branch channel 2a and the third branch channel 2c, and
- the outlet end 6b of the circulation flow path 6 and the outflow flow path 5 communicate with each other via the fourth branch flow path 2d and the second branch flow path 2b to form an open flow path (open system).
- the second communication state is established.
- the branch member (flexible branch portion) 2 is pinched in the 3 (ii) direction. That is, the second branch passage 2b is pinched by the second pressing portion 3a22 and the first NO side member 3b21 (not shown in FIG. 8) constituting the pinch member (pressing member) 3a2, and the third pressing The first branch flow path 2a is pinched by the portion 3a23 and the second NO side member 3b22.
- the inlet side end 6a of the circulation channel 6 and the outlet side end 6b of the circulation channel 6 are communicated (conducted) via the third branch channel 2c and the fourth branch channel 2d, thereby circulating the flow.
- a path (closed system) is formed, and the first communication state is established.
- the switching operation from the second communication state to the first communication state by the communication state switching unit 3 at the time of liquid replacement is the same as that in FIG.
- FIG. 7 is more advantageous than the configuration of the channel module 1 shown in FIG. 7 in that the configuration of the channel module 1 shown in FIG. 8 can smoothly perform liquid feeding during circulation (first communication state). This is because the inlet end 6a of the circulation channel 6 and the outlet end 6b of the circulation channel 6 are arranged to face each other.
- the configuration of the flow path module 1 shown in FIG. 7 as with the flow path module 1 shown in FIG. 8, four branch flow paths (first branch flow path 2a to fourth branch flow path) are high. Since there is no crossing in the vertical direction, there is an advantage that planar arrangement is possible. Accordingly, which one of the flow path module 1 shown in FIG. 7 and the flow path module 1 shown in FIG. 8 is used may be determined in accordance with a request required for the apparatus.
- the control of the pump 7 becomes easy.
- the liquid feeding direction at the time of liquid replacement is the same as the liquid feeding direction at the time of circulation, and the liquid feeding direction may be changed according to the purpose.
- FIG. 9 is a schematic configuration diagram of a flow channel module of Example 2 according to another embodiment of the present invention, showing a second communication state
- FIG. 10 is a schematic diagram of the flow channel module of Example 2.
- It is a block diagram, Comprising: It is a figure which shows a 1st communication state.
- the pinch member (pressing member) (3a, 3a1, 3a2) and the movable iron core 3c constituting the communication state switching unit 3 are moved up and down in one direction (vertical direction), so that the pinch member and The branch member (flexible branch portion) 2 is crushed (pinched) in cooperation with the support member that always maintains a stationary state, and the first communication state and the second communication state are switched.
- the pinch member (pressing member) is configured to switch between the first communication state and the second communication state by rotating around the hinge (fulcrum) with respect to the support member.
- the point is different.
- Other components are the same as those in the first embodiment, and the description overlapping with the first embodiment is omitted below. 9 and 10, the same reference numerals are given to the same components as those in the first embodiment.
- FIG. 9 shows a top view of the flow path module 1 in the upper diagram, and a cross-sectional view along the line AA in the upper diagram in the lower diagram.
- the flow channel module 1 includes a branch member (flexible branch portion) 2 and a communication state switching portion 8.
- the communication state switching unit 8 has an opening / closing member including a pinch member (pressing member) 8a and a support member 8b that maintains a stationary state at all times.
- the pinch member 8a has a T-shape in a plan view or a vertical projection plane, a first pressing portion 8a1 extending in one direction, and a second pressing portion extending in a direction perpendicular to the first pressing portion 8a1. 8a2.
- the support member 8b has a cross-like shape in plan view, a portion extending in one direction while facing the first pressing portion 8a1 constituting the pinch member 8a, and a second pressing portion 8a2 constituting the pinch member 8a. And a portion extending in the other direction while facing.
- the pinch member 8 a is connected to one end of the first pressing portion 8 a 1 at a substantially central portion of the second pressing portion 8 a 2.
- the second pressing portion 8a2 is inclined upward at a predetermined angle from the connecting portion with the first pressing portion 8a1, bent at a predetermined position, and has a predetermined angle. And has a cross-sectional shape inclined downward.
- the pinch member 8a and the support member 8b are connected via a hinge 8c provided on the support member 8b. A location where the pinch member 8a is connected to the hinge 8c is a connecting portion between the first pressing portion 8a1 and the second pressing portion 8a2.
- the pinch member 8a rotates in an arc shape with the hinge 8c as a fulcrum, that is, in one direction that follows the arc-shaped track
- the first pressing portion 8a1 constituting the pinch member 8a and the first The two pressing portions 8a2 are rotated in an arc shape in opposite directions.
- the driving force for the pinch member 8a to rotate in an arc shape with the hinge 8c as a fulcrum is supplied by, for example, a motor (not shown) or a driving mechanism that combines a direct acting mechanism such as a spring and an electromagnetic valve.
- the pinch member 8a and the support member 8b only need to have rigidity, and are formed of, for example, stainless steel, iron, or resin.
- the branch member (flexible branch portion) 2 includes a third branch channel 2 c connected to the inlet side end 6 a of the circulation channel 6 and an outlet of the circulation channel 6.
- the first branch flow path 2a and the second branch flow path 2b are arranged on the support member 8b facing the second pressing portion 8a2.
- the channel lengths of the first branch channel 2a and the second branch channel 2b are longer than the channel lengths of the third branch channel 2c and the fourth branch channel 2d.
- the state shown in FIG. 9 is that the first pressing portion 8a1 and the supporting member 8b of the pinch member 8a constituting the opening / closing member are joined to the corner portion where the first branch passage 2a and the second branch passage 2b are joined,
- the branching member (flexible branching portion) 2 is pinched diagonally in plan view so as to cross the corner where the third branching channel 2c and the fourth branching channel 2d are joined.
- the inflow end 4a of the inflow passage 4 and the circulation passage 6 communicates (conducts) via the first branch passage 2a and the third branch passage 2c, and the circulation passage 6
- the outlet end 6b and the outflow channel 5 are communicated (conducted) via the fourth branch channel 2d and the second branch channel 2b to form an open channel (open system), and the second communication state It becomes.
- FIG. 10 shows a state where the communication state switching unit 8 has switched to the first communication state.
- FIG. 10 is a top view of the flow path module 1 in the upper diagram, and a lower sectional view taken along the line BB in the upper diagram.
- a motor not shown
- a drive mechanism combining a spring and a direct acting mechanism such as an electromagnetic valve is used.
- the pinch member (pressing member) 8a rotates in an arc shape with the hinge 8c as a fulcrum.
- the first pressing portion 8a1 constituting the pinch member 8a has a corner portion where the first branch flow channel 2a and the second branch flow channel 2b are joined together with the support member 8b, From the state where the branch member (flexible branch portion) 2 is pinched diagonally in plan view so as to cross the corner where the branch flow channel 2c and the fourth branch flow channel 2d are joined, the hinge 8c is used as a fulcrum. It turns upward in an arc. In response to the rotation of the first pressing portion 8a1, the second pressing portion 8a2 constituting the pinch member 8a rotates downward in an arc shape. Then, as shown in the upper and lower views of FIG.
- the second pressing portion 8a2 cooperates with the support member 8b to form the first branch flow path 2a constituting the branch member (flexible branch portion) 2 and
- the second branch channel 2b is pinched simultaneously.
- the inlet side end 6a of the circulation channel 6 and the outlet side end 6b of the circulation channel 6 are communicated (conducted) via the third branch channel 2c and the fourth branch channel 2d, thereby circulating the flow.
- a path (closed system) is formed, and the first communication state is established.
- the lower diagram of FIG. 10 is a cross-sectional view taken along the line BB of the upper diagram. Therefore, a branch member (flexible branch portion) 2 is formed on the upper surface of the support member 8b that maintains a stationary state at all times. Shown to be placed. However, it is actually the branch member (flexible branch portion) 2 that is disposed on the support member 8 b that extends while facing the first press portion 8 a 1 that constitutes the pinch member (press member) 2. Among them, the first branch channel 2a and the second branch channel 2b are joined from the corner where the third branch channel 2c and the fourth branch channel 2d are joined through the center of the branch member 2. This is the range up to the corner.
- the support member 8b has a cross-like shape in plan view, but the present invention is not necessarily limited thereto.
- it comprises a portion extending in one direction while facing the first pressing portion 8a1 constituting the pinch member 8a, and a portion extending in the other direction facing the second pressing portion 8a2 constituting the pinch member 8a.
- the support member 8b may be formed so as to be disposed at a position facing the second pressing portion 8a2 so as to form a T shape in plan view.
- the open / close member composed of the pinch member and the support member is formed without considering interference or contact between the pinch member (pressing member) and the support member as in the first embodiment. Is possible. Thereby, compared with Example 1, it becomes possible to implement
- FIG. 11 is a schematic configuration diagram of the flow path module of the third embodiment according to another embodiment of the present invention, and shows a switching operation from the second communication state to the first communication state.
- a plurality of rollers (pressing members) and a branching member (flexible branching portion) 2 are sandwiched, and a flat plate-like supporting member is arranged on the opposite side of the plurality of rollers to constitute an opening / closing member.
- This is different from the first and second embodiments described above. Since other components are the same as those in the first embodiment, a description overlapping with that in the first embodiment is omitted below.
- the same components as those in the first and second embodiments are denoted by the same reference numerals.
- the flow channel module 1 of the present embodiment includes a branch member (flexible branch portion) 2 and a communication state switching portion 9.
- the branch member (flexible branch portion) 2 includes a first branch channel 2a connected to the inflow channel 4, a second branch channel 2b connected to the outflow channel 5, and a circulation channel 6 (not shown).
- the first branch channel 2a and the fourth branch channel 2d are arranged to communicate with each other while facing each other, and the second branch channel 2b and the third branch channel 2c are arranged to communicate with each other while facing each other.
- the channel lengths of the first branch channel 2a and the second branch channel 2b are longer than the channel lengths of the third branch channel 2c and the fourth branch channel 2d. .
- the open / close member constituting the communication state switching unit 9 is arranged in the depth direction with respect to the branch member (flexible branch portion) 2, and includes a flat plate-like support member (not shown) and a branch member (possible Three rollers 9a1 (hereinafter referred to as first rollers), 9a2 (hereinafter referred to as first rollers), which are arranged above the flexible branch portion 2 and are rotatably supported by a rectangular or linear or rod-like connecting member 9b. , Referred to as a second roller), and 9a3 (hereinafter referred to as a third roller).
- the connecting member 9b includes a corner portion where the first branch channel 2a and the second branch channel 2b are joined, and a corner portion where the third branch channel 2c and the fourth branch channel are joined.
- Two line or bar-like portions that are parallel to a line segment (hereinafter referred to as a diagonal line of the branching member 2) and that are spaced apart from each other at a predetermined interval and that are opposed to each other, and these two lines or bars.
- the two ends of the unit are connected to each other, and are constituted by two other linear or bar-like parts that are spaced apart from each other at a predetermined interval and face each other.
- the first roller 9a1 is rotatably supported by one linear or rod-like portion arranged so as to be parallel to the diagonal line of the branch member 2, and the first linear or rod-like portion is supported by the other linear or rod-like portion.
- Two rollers 9a2 and a third roller 9a3 are rotatably supported.
- the left side linear or rod-like portion of the two sides arranged to be parallel to the diagonal line of the branching member 2, the first roller 9 a 1 on the upper side from the longitudinal center, and the right side
- the second roller 9a2 is disposed above the central portion in the longitudinal direction
- the third roller 9a2 is disposed below the central portion in the longitudinal direction.
- the second roller 9a2 and the third roller 9a3 are spaced apart from each other with a slight gap along the longitudinal direction.
- the first roller 9a1, the second roller 9a2, and the third roller 9a3 have substantially the same length in the longitudinal direction, and the corner portion where the first branch channel 2a and the second branch channel 2b are joined. And it has the length more than the length of the line segment which connects the corner
- the lengths of the three rollers 9a1 to 9a3 in the longitudinal direction are set to lengths suitable for crushing (closing) the first branch flow path 2a and the second branch flow path 2b described later. ing.
- the area of the flat support member (not shown) is at least larger than the area of the maximum circumscribed rectangle of the branch member (flexible branch portion) 2, so that the branch member (flexible member) is formed on the flat support member.
- a branch member 2 can be placed (arranged) between the support member and the first roller 9a1 to the third roller 9a3 and a connecting member 9b that rotatably supports and connects them.
- (Flexible branch portion) 2 is configured to be movable in one direction while sandwiching it. A force or a load is always applied to the first roller 9a1 to the third roller 9a3 in the direction in which the branch member (flexible branch portion) 2 is crushed.
- the inflow end 4a of the inflow passage 4 and the circulation passage 6 communicates (conducts) via the first branch passage 2a and the third branch passage 2c, and the circulation passage 6
- the outlet end 6b and the outflow channel 5 are communicated (conducted) via the fourth branch channel 2d and the second branch channel 2b to form an open channel (open system), and the second communication state It becomes.
- the first branch flow path 2a is crushed (closed) by the cooperation of the first roller 9a1 and the flat plate-shaped support member, and at the same time, the second roller 9a2 and the flat plate
- the second branch flow path 2b is crushed (closed) by cooperation with the support member.
- the first roller 9a1 is disposed on the left linear or rod-like portion constituting the connecting member 9b, and the second roller 9a2 and the third roller 9a3 are provided on the right side constituting the connecting member 9b.
- the 3rd roller 9a3 is good also as a left linear or rod-shaped part which comprises the connection member 9b, Comprising: It is good also as a structure arrange
- both ends of the linear or rod-like portions of the two sides constituting the connecting member 9b that rotatably support the first roller 9a1 to the third roller 9a3 are connected to each other and spaced apart from each other at a predetermined interval.
- the other two sides of the linear or bar-like portion are formed in a straight line, but are not necessarily limited thereto.
- the other two sides are formed in a circular arc shape, the two sides of the linear or bar-like portion that supports the first roller 9a1 to the third roller 9a3 rotatably can be connected. It is good also as a shape.
- the first roller 9a1 to the third roller 9a3, the connecting member 9b that rotatably supports them, and the flat support member are made of, for example, stainless steel, iron, resin, or the like having rigidity. Can be formed.
- the first roller 9a1 to the third roller 9a3 move in the horizontal direction to switch the communication state of the branch member (flexible branch portion), that is, the configuration to switch the communication state by the slide method. Therefore, compared with Example 1 and Example 2, it is expected that the switching time for switching from the second communication state to the first communication state will be somewhat longer. However, in this embodiment, since the communication state can be switched by sliding in one direction within the horizontal plane, further simplification can be achieved.
- FIG. 12 is a schematic configuration diagram of the flow path module of the fourth embodiment according to another embodiment of the present invention, and shows a switching operation from the second communication state to the first communication state.
- the flow of a liquid such as a culture solution that flows through the branch member (flexible branch portion) is indicated by a dotted arrow.
- the opening / closing member is constituted by a flat support member (not shown) disposed on the opposite side of the two rollers with the two rollers (pressing member) and the branching member (flexible branching portion) interposed therebetween.
- the opening / closing member is constituted by a flat support member (not shown) disposed on the opposite side of the two rollers with the two rollers (pressing member) and the branching member (flexible branching portion) interposed therebetween.
- the flow path module 1 of this embodiment includes a branch member (flexible branch portion) 2 ′ and a communication state switching portion 10.
- the branch member (flexible branch) 2 ′ includes a first branch channel 2 a connected to the inflow channel 4, and a third branch channel connected to the inlet end 6 a of the branch channel 6 (not shown). 2c, a fourth branch channel 2d connected to the outlet end 6b of the branch channel 6, and a second branch channel 2b connected to the outflow channel 5, and these four branch channels Are adjacent to each other in the order described above, and all are aligned in the same direction.
- the first branch flow channel 2a to the fourth branch flow channel 2d are arranged on the same side surface of the branch member (flexible branch portion) 2 'having a square shape in plan view.
- the first branch flow path is formed in order from the lower side in three flow path walls extending horizontally from the right side surface of the branch member (flexible branch section) 2 ′ to the center side. 2a, a third branch channel 2c, a fourth branch channel 2d, and a second branch channel 2b are defined.
- These four branch channels are in the region from the left end of the three channel walls (the end on the center side of the branch member) to the left side of the branch member (flexible branch) 2 ′. They can communicate with each other.
- the three flow path walls are formed, for example, by folding one flexible sheet and ultrasonic welding or heat welding.
- the open / close member constituting the communication state switching unit 10 is arranged in the depth direction with respect to the branch member (flexible branch portion) 2 ′, and includes a flat plate-like support member (not shown) and a branch member (not shown).
- Two rollers 10a1 (hereinafter referred to as first rollers) and 10a2 which are arranged above the flexible branch portion 2 'and are rotatably supported by a rectangular or linear or rod-like connecting member 10b. (Hereinafter referred to as the second roller).
- the connecting member 10b is parallel to the three flow path walls, and is separated from each other by a predetermined interval and is opposed to the two linear or rod-shaped portions, and the three flow path walls are orthogonal to each other.
- the first roller 10a1 is rotatably supported by one linear or rod-like portion arranged so as to be parallel to the three flow path walls, and the second roller 10a2 is rotatable by the other linear or rod-like portion. It is supported by.
- the interval between the two sides that rotatably support the first roller 10a1 and the second roller 10a2 coincides with the interval between the two channel walls arranged on the outside of the three channel walls. . That is, a flow path wall that defines the first branch flow path 2a and the third branch flow path 2c, and a flow path wall that defines the fourth branch flow path 2d and the second branch flow path 2b It is the same as the interval. Further, the lengths of the first roller 10a1 and the second roller 10a2 in the longitudinal direction are at least from the left end portion (end portion on the center side of the branch member) of the three flow path walls to the branch member (flexible branch portion). Longer than 2 'left side.
- the area of the flat support member (not shown) is at least larger than the area of the branching member (flexible branching portion) 2 ′ and covers an area where the connecting member 10 b is disposed. Accordingly, the branch member (flexible branch portion) 2 ′ can be placed (arranged) on the flat support member, and the first roller 10a1 and the second roller 10a2 are rotatably supported and connected.
- the connecting member 10b is configured to be movable in one direction while sandwiching a branch member (flexible branch portion) 2 ′ between the support member and the support member. Note that a force or a load is always applied to the first roller 10a1 and the second roller 10a2 in the direction in which the branch member (flexible branch portion) 2 'is crushed.
- the outlet end 6b of the circulation flow path 6 and the outflow flow path 5 communicate with each other via the fourth branch flow path 2d and the second branch flow path 2b, so that an open flow path (open system) ) Is formed, and the second communication state is established.
- the liquid such as the culture solution flows back on the left side surface of the branch member (flexible branch portion) 2 ′.
- the connecting member 10b that rotatably supports and connects the first roller 10a1 and the second roller 10a2 by an actuator (not shown) is connected in the horizontal direction (from the upper side to the lower side in FIG. 12).
- the state after moving in the direction of the heading is shown in the right figure of FIG.
- the center part of the flow path wall which defines the 2nd branch flow path 2b and the 4th branch flow path 2d by cooperation of the 1st roller 10a1 and a flat support member As shown in the right figure of FIG. 12, the center part of the flow path wall which defines the 2nd branch flow path 2b and the 4th branch flow path 2d by cooperation of the 1st roller 10a1 and a flat support member.
- the liquid such as the culture solution once collides with the left side surface of the branch member (flexible branch portion) 2 ′, and then flows back. Therefore, although not necessarily desirable from the viewpoint of streamlines, all the flow paths of the first branch flow path 2a to the fourth branch flow path 2d are aligned. Can be easily connected.
- the four branch flow paths (2a to 2d) have the same flow path width, so that only two rollers functioning as pressing parts can be provided. Can be reduced.
- FIG. 13 is a schematic block diagram of the flow-path module of Example 5 which concerns on the other Example of this invention.
- the arrangement relationship or connection of the first branch flow path 2a to the fourth branch flow path 2d constituting the branch member (flexible branch section) 2 is compared with the first to fourth embodiments described above. The relationship is different. Since other components are the same as those in the first embodiment, a description overlapping with that in the first embodiment is omitted below.
- the 13 includes a branch member (flexible branch portion) 2 and a communication state switching portion 3 shown in FIG. 5 of the first embodiment.
- the branching member (flexible branching portion) 2 is connected to a third branching channel 2c connected to an inlet side end 6a of the circulation channel 6 (not shown) and an outlet side end 6b of the circulation channel 6.
- the fourth branch flow channel 2d communicates with each other while facing each other, and the third branch flow channel 2c and the fourth branch flow channel 2d are arranged in a straight line.
- the first branch channel 2a connected to the inflow channel 4 has a third branch channel 2c and a fourth branch channel 2d arranged linearly at a predetermined angle (acute angle). It is joined to the approximate center part of.
- the second branch channel 2b connected to the outflow channel 5 has a third branch channel 2c and a fourth branch channel arranged linearly at a predetermined angle (acute angle). Joined to approximately the center of 2d.
- the first branch channel 2a and the second branch channel 2b are arranged on the same side in plan view with respect to the third branch channel 2c and the fourth branch channel 2d arranged in a straight line.
- the open / close member constituting the communication state switching unit 3 is configured by the pinch member (pressing member) 3a1 shown in FIG. 5 of the first embodiment and the support member 3b 'that always maintains a stationary state.
- the first pressing portion 3a11 constituting the pinch member (pressing member) 3a1 and the NC side member 3b1 (not shown in FIG. 13) constituting the support member 3b ′ are branched members (flexible) (Branch portion) 2 is pinched (crushed), and the inflow end passage 4 and the inlet end portion 6a of the circulation passage 6 communicate with each other via the first branch passage 2a and the third branch passage, The outlet end 6b of the circulation flow path 6 and the outflow flow path 5 are communicated via the fourth branch flow path 2d and the second branch flow path 2b to form an open flow path (open system).
- the angle formed between the first branch flow path 2a and the third branch flow path is appropriately set within a range where the flow path resistance does not increase as much as possible.
- the first branch flow path 2a is pinched by the second pressing portion 3a12 and the NO side member 3b2 ′ (not shown in FIG. 13) constituting the pinch member (pressing member) 3a1.
- the second branch passage 2b is pinched by the third pressing portion 3a13 and the NO-side member 3b2 ′.
- the inlet side end 6a of the circulation channel 6 and the outlet side end 6b of the circulation channel 6 are connected via the third branch channel 2c and the fourth branch channel 2d arranged in a straight line. Since communication (conduction) is made and a circulation channel (closed system) is formed, the flow of the circulation channel becomes smooth.
- the branching member (flexible branching portion) 2 and the communication state switching portion 3 shown in FIG. 6 of the first embodiment are partially modified.
- the branch member (flexible branch portion) 2 the first branch flow path 2 a and the fourth branch flow path 2 d are parallel to each other and spaced apart from each other by a predetermined distance.
- the second branch flow path 2b and the third branch flow path 2c are parallel to each other and spaced apart from each other by a predetermined distance, and the third branch flow path 2c and the fourth branch flow path 2d. are arranged in a straight line.
- the first pressing part 3a21, the second pressing part 3a22 ′, and the third pressing part 3a23 ′ constituting the pinch member (pressing member) It becomes possible to arrange in a straight line in the vertical projection plane.
- the second pressing portion 3a22 ′ and the third pressing portion 3a23 ′ are arranged below the first pressing portion 3a21 by a predetermined distance, so that a single pinch member (pressing member) can be used as a branching member (flexible member). It is possible to pinch three portions of the branching portion 2, and it is possible to simplify the shape of the pinch member or reduce the number of components of the pinch member as compared with the first embodiment.
- the branch member (flexible branch portion) 2 includes a first branch flow path 2a and a second branch flow path 2b arranged in a straight line, and a third branch flow path 2c and a fourth branch flow.
- the path 2d is arranged in a straight line, and has a configuration in which these are arranged so as to be joined at a predetermined angle.
- the branch member (flexible branch portion) 2 is linearly arranged when the third branch channel 2c and the fourth branch channel 2d arranged in a straight line are used as a reference.
- the first branch flow path 2a and the second branch flow path 2b are joined while being inclined.
- the branch member (flexible branch portion) 2 includes a third branch channel 2c and a fourth branch channel 2d arranged in a straight line, and the third branch channel 2c and the fourth branch channel.
- the first branch flow path 2a and the second branch flow path 2b arranged to be orthogonal to 2d have a shape that is offset. In other words, the first branch flow path 2a and the second branch flow path 2b are arranged in a straight line.
- FIG. 14 is an overall schematic configuration diagram of a cell culture device having a flow path module of Example 6 according to another embodiment of the present invention
- FIG. 15 is a diagram showing a modification of the cell culture device shown in FIG. It is.
- the configuration of the flow channel module 1 shown in FIG. 7 in the first embodiment will be described as an example, but the configuration of the flow channel module 1 shown in FIG. 8 or the second to fifth embodiments has been described. The same applies to any of the configurations of the flow path module.
- FIG. 14 and FIG. 15 the same reference numerals are given to the same components as those shown in the first embodiment, and the description overlapping with the first embodiment is omitted below.
- the cell culture device 20 includes a supply bag that stores a cell suspension 21, a supply bag that stores a culture medium 22, a HEPA filter 23, a channel switching unit 24, a channel module 1, and a circulation channel. 6.
- a pump 7 such as a squeezing pump installed in the circulation channel 6, a culture vessel 25 installed downstream of the pump 7 and in the circulation channel 6, and a medium or culture solution used for culture A recovery bag 26 for recovery is provided.
- the cell culture device 20 performs culture by automatically performing cell seeding and medium exchange.
- the cell suspension 21 or the culture medium 22 is introduced into the circulation channel 6 via the channel module 1 and circulates in the circulation channel 6 in which the culture vessel 25 is installed, thereby forming a closed system. Forming. In this way, by culturing in the circulation channel 6 forming a closed system, contamination from the outside can be prevented and highly reliable culture can be performed.
- the cell suspension 21 or the culture medium 22 is introduced into the inflow channel 4 and selectively fed by the channel switching unit 24. Further, the HEPA filter 23 can be selectively connected to the inflow channel 4 by the channel switching unit 24, and the liquid that remains in the channel or flows through the channel by the air that passes through the HEPA filter 23. It can be extruded.
- the inflow passage 4 is connected to the first branch passage 2a of the branch member (flexible branch portion) 2, and the outflow passage 5 whose one end is connected to the recovery bag 26 is the branch member (flexible branch portion). 2 is connected to the second branch channel 2b.
- the inlet end 6a of the circulation channel 6 is connected to the third branch channel 2c of the branch member (flexible branch) 2, and the deriving end 6b of the circulation channel 6 is connected to the branch member (flexible member).
- Sexual branch portion) 2 is connected to the fourth branch flow path 2d.
- the branch member (flexible branch portion) 2 is moved in the 3 (i) direction by turning off the coil 3f constituting the communication state switching portion 3 shown in FIG. Crush (pinch). That is, the first branching is performed at the first pressing portion 3a11 constituting the pinch member (pressing member) 3a1 and the NC side member 3b1 (not shown in FIG. 14) constituting the support member 3b ′ shown in FIG.
- a branch member diagonally in plan view so as to cross the corner where the channel 2a and the second branch channel 2b join and the corner where the third branch channel 2c and the fourth branch channel 2d join. (Flexible branch) 2 is pinched.
- the inflow end 4a of the inflow passage 4 and the circulation passage 6 communicates with each other via the first branch passage 2a and the third branch passage 2c, and the exit end of the circulation passage 6
- the part 6b and the outflow channel 5 are communicated with each other via the fourth branch channel 2d and the second branch channel 2b, so that an open channel (open system) is formed and a second communication state is established.
- the inside of the branching member (flexible branching portion) 2 becomes negative pressure, and the cell suspension 21 or the medium 22 is first supplied from the inflow channel 4. 1 is sucked into one branch channel 2a.
- the cell suspension 21 or the culture medium 22 sucked into the first branch flow path 2a is introduced into the inlet end 6a of the circulation flow path 6 via the third branch flow path 2c.
- the culture vessel 25 installed in the circulation channel 6 it flows into the fourth branch channel 2 d from the outlet end 6 b of the circulation channel 6. Thereafter, the fourth branch flow path 2 d and the second branch flow path 2 b are flowed to the outflow flow path 5 and sent to the recovery bag 26.
- the second communication state is continued by the communication state switching unit 3 described above.
- the coil 3f shown in FIG. Part 2 is pinched in the 3 (ii) direction. That is, while pinching the 1st branch flow path 2a in 2nd press part 3a12 and NO side member 3b2 '(not shown in FIG. 14) which comprise the pinch member (pressing member) 3a1 shown in FIG.
- the second branch passage 2b is pinched by the third pressing portion 3a13 and the NO side member 3b2 ′.
- a path (closed system) is formed and switched to the first communication state.
- fluid shearing force can be applied by circulating the cell suspension 21 or the culture medium 22 in the circulation channel 6 in the first communication state.
- FIG. 15 is an overall schematic configuration diagram of the cell culture apparatus 20 ′ that has the buffer tank 27 on the downstream side of the culture vessel 25 in the circulation channel 6.
- the channel volume is uniquely determined by the channel diameter (inner diameter) and the channel length, so that it is difficult to flexibly cope with the culture amount. Therefore, a buffer tank 27 is installed in the circulation channel 6 so that the culture amount can be changed flexibly.
- the buffer tank 27 is installed in the circulation channel 6 on the downstream side of the culture vessel 25, and includes a tank housing 27a, an inflow port 27b, an outflow port 27c, and an air exhaust port 27d.
- the outflow port 27c is provided in the lower part of the tank casing 27a, and the air discharge port 27d is provided in the upper part of the tank casing 27a.
- the cell suspension 21 or the culture medium 22 is sent to the circulation channel 6 via the channel module 1, the cell suspension 21 or the culture medium 22 is made to flow downstream from the circulation channel 6 through the outflow port 27c.
- the second communication state is set by the communication state switching unit 3, and the branch member (flexible branch unit)
- the exhaust gas is exhausted via the second fourth branch flow path 2d, the second branch flow path 2b, and the outflow flow path 5. Switching between the outflow port 27c and the air discharge port 27d is selectively performed by the switching valve 28.
- the installation position of the inflow port 27b is not necessarily limited to the upper part of the tank casing 27a.
- the cell culture device 20 has the HEPA filter 23.
- the HEPA filter 23 is not essential, and instead of the HEPA filter 23, for example, a bag for storing system water such as pure water is provided. It is also good.
- the medium is preferably exchanged by allowing the system water to flow through the circulation channel 6 via the branch member (flexible branch part) 2 and to be discharged via the outflow channel 5. Can be performed.
- a cell culture device capable of feeding a cell suspension or a medium into a circulation channel while preventing air bubbles from mixing.
- a desired culture amount can be obtained by installing a buffer tank in the circulation channel.
- FIG. 16 is an overall schematic configuration diagram of a turbidimeter having a flow path module of Example 7 according to another example of the present invention.
- the configuration of the flow channel module 1 shown in FIG. 7 in the first embodiment will be described as an example, but the configuration of the flow channel module 1 shown in FIG. 8 or the second to fifth embodiments has been described. The same applies to any of the configurations of the flow path module.
- the same components as those shown in the first embodiment are denoted by the same reference numerals, and the description overlapping with the first embodiment is omitted below.
- the turbidimeter 30 includes an inlet 34 for introducing a liquid having an unknown turbidity, a flow path module 1, a circulation flow path 6, and a squeezing pump installed in the circulation flow path 6.
- the flow cell 31 installed in the circulation channel 6 on the downstream side of the pump 7, the light source 32 for irradiating the liquid flowing through the flow cell 31, and the opposite side of the light source 32 across the flow cell 31
- a detector 33 is provided, and an outflow passage 5 for sending the liquid whose turbidity is measured to the outlet 35.
- the branch member (flexible branch portion) 2 is crushed (pinched) in the 3 (i) direction by turning off the coil 3f constituting the communication state switching portion 3 shown in FIG. That is, the first branching is performed at the first pressing portion 3a11 constituting the pinch member (pressing member) 3a1 and the NC side member 3b1 (not shown in FIG. 16) constituting the support member 3b ′ shown in FIG.
- the inflow end 4a of the inflow passage 4 and the circulation passage 6 communicates with each other via the first branch passage 2a and the third branch passage 2c, and the exit end of the circulation passage 6
- the part 6b and the outflow channel 5 are communicated with each other via the fourth branch channel 2d and the second branch channel 2b, so that an open channel (open system) is formed and a second communication state is established.
- the inside of the branch member (flexible branch portion) 2 becomes negative pressure, and the liquid having an unknown turbidity introduced from the inlet 34 is Suction from the inflow channel 4 into the first branch channel 2a.
- the liquid having an unknown turbidity sucked into the first branch flow path 2a is introduced into the inlet end 6a of the circulation flow path 6 via the third branch flow path 2c and passes through the circulation flow path 6. It flows through the flow cell 31 installed downstream of the pump 7. At this time, light is emitted from the light source 32 toward the liquid flowing through the flow cell 31, and the transmitted light and / or scattered light is received by the detector 33, and turbidity is determined based on the light intensity of the transmitted light and / or scattered light.
- the liquid whose turbidity has been measured is discharged from the deriving end 6a of the circulation flow path 6 to the fourth branch flow path 2d, the second branch flow path 2b, and the outflow of the branch member (flexible branch section) 2. It is discharged from the outlet 35 through the flow path 5.
- the branch member (flexible branch portion) 2 is pinched in the 3 (ii) direction by energizing the coil 3f shown in FIG. That is, while pinching the 1st branch flow path 2a in 2nd press part 3a12 and NO side member 3b2 '(not shown in FIG. 16) which comprise the pinch member (pressing member) 3a1 shown in FIG.
- the second branch passage 2b is pinched by the third pressing portion 3a13 and the NO side member 3b2 ′.
- the inlet end 6a of the circulation channel 6 and the outlet end 6b of the circulation channel 6 communicate with each other via the third branch channel 2c and the fourth branch channel 2d.
- System is formed and switched to the first communication state.
- the liquid flows through the circulation flow path 6, and the liquid again flows through the flow cell 31.
- light is irradiated from the light source 32 toward the liquid flowing through the flow cell 31, and the transmitted light and / or scattered light is transmitted.
- the detector 33 receives light, and turbidity is measured based on the light intensity of transmitted light and / or scattered light.
- the communication state switching unit 3 switches to the second communication state, and the liquid whose turbidity is measured is the fourth branch flow of the branch member (flexible branch unit) 2. It is discharged from the outlet 35 through the path 2d, the second branch channel 2b, and the outflow channel 5.
- the flow cell, the light source, and the detector that are set in the circulation flow path are introduced into the circulation flow path by bringing the liquid having unknown turbidity into the second communication state at the communication state switching unit.
- Turbidity can be easily measured by a turbidity detection mechanism comprising Also, even if the liquid has low turbidity, or even if turbidity cannot be measured once due to disturbance noise such as ambient light, the communication state switching unit switches to the first communication state. By circulating the liquid in the circulation channel, turbidity can be reliably measured.
- FIG. 17 is an overall schematic configuration diagram of a cell dispersing apparatus having a flow path module according to an eighth embodiment according to another embodiment of the present invention.
- the configuration of the flow channel module 1 shown in FIG. 7 in the first embodiment will be described as an example, but the configuration of the flow channel module 1 shown in FIG. 8 or the second to fifth embodiments has been described. The same applies to any of the configurations of the flow path module.
- the same components as those shown in the first embodiment are denoted by the same reference numerals, and the description overlapping with that in the first embodiment is omitted below.
- the cell dispersion device 40 is installed in the inlet 46, the channel module 1, the circulation channel 6, and the circulation channel 6 for introducing a cell suspension whose degree of cell dispersion is unknown.
- a pump 7 such as a squeezing pump
- an orifice 41 downstream of the pump 7 and installed in the circulation channel 6 a flow cell 43 installed downstream of the orifice 41 and in the circulation channel 6, and in the flow cell 43
- a light source 44 for irradiating light to the cell suspension flowing therethrough a detector 45 installed on the opposite side of the light source 44 across the flow cell 43, and installed in the circulation channel 6 downstream of the flow cell 43
- a buffer tank 47 an outlet 48 for discharging a cell suspension in which cells are uniformly dispersed
- a control unit 42 for controlling the control unit 42.
- the cell dispersion device 40 takes in a cell suspension whose degree of cell dispersion is unknown from the inflow port 46, disperses the cell clumps inside, and produces a cell suspension in which cells are uniformly dispersed from the outflow port 48. Has the function of discharging.
- the orifice 41 installed in the circulation channel 6 on the downstream side of the pump 7 forms a channel constriction. The orifice 41 abruptly changes the flow path cross-sectional area, thereby applying a strong shearing force to the cell suspension flowing through the inside, and promoting the dispersion of the cell clumps.
- the diameter of the orifice 41 (cross-sectional diameter) is generally in the range of 0.5 mm to 1 mm in view of the size of the cells being about 10 ⁇ m, it is preferable because the cell clumps can be efficiently dispersed. Further, the orifice diameter may be changed to be suitable for each cell based on the size and adhesion of the cell. If an orifice made of an inexpensive resin is used as the orifice 41, the entire flow path is made disposable if necessary, that is, a disposable orifice, which is desirable from the viewpoint of preventing contamination.
- the flow cell 43 provided in the circulation channel 6 on the downstream side of the orifice 41 measures the light intensity as data relating to the degree of dispersion of the cell clumps when the cell suspension flows through the flow cell. .
- Light is emitted from the light source 44 toward the flow cell 43, and the transmitted light and / or scattered light is detected by the detector 45.
- the light source 44, the flow cell 43, and the detector 45 constitute a cell dispersion degree measuring device.
- the amount of the transmitted light and / or scattered light observed from the flow cell 43 changes as the cell dispersion degree of the cell suspension changes.
- the amount of change of the light intensity value becomes small, and based on the fact that it converges to a constant value (preferably a predetermined target value). It becomes possible to determine that cell dispersion has been performed.
- the control unit 42 determines whether or not the cells have reached a predetermined degree of dispersion. If the degree of dispersion has not been reached, the controller 7 drives the pump 7. continue.
- the shearing force applied to the cell suspension may be changed by changing the liquid feeding speed of the pump 7.
- the communication state switching unit 3 shown in FIG. By making the coil 3f constituting the non-energized state, the branch member (flexible branch portion) 2 is crushed (pinched) in the 3 (i) direction. That is, the first branching is performed at the first pressing portion 3a11 constituting the pinch member (pressing member) 3a1 and the NC side member 3b1 (not shown in FIG. 17) constituting the support member 3b ′ shown in FIG.
- a branch member diagonally in plan view so as to cross the corner where the channel 2a and the second branch channel 2b join and the corner where the third branch channel 2c and the fourth branch channel 2d join. (Flexible branch) 2 is pinched.
- the inflow end 4a of the inflow passage 4 and the circulation passage 6 communicates with each other via the first branch passage 2a and the third branch passage 2c, and the exit end of the circulation passage 6
- the part 6b and the outflow channel 5 are communicated with each other via the fourth branch channel 2d and the second branch channel 2b, so that an open channel (open system) is formed and a second communication state is established.
- the inside of the branch member (flexible branch part) 2 becomes negative pressure, and the cell suspension introduced from the inflow port 46 becomes an inflow channel. 4 is sucked into the first branch channel 2a.
- the cell suspension sucked into the first branch channel 2a is introduced into the inlet end 6a of the circulation channel 6 through the third branch channel 2c and flows through the circulation channel 6. It flows through the orifice 41 and the flow cell 31 installed on the downstream side of the pump 7.
- the configuration and operation of the buffer tank 47 are the same as those in the sixth embodiment shown in FIG.
- the degree of cell dispersion As a method of measuring the degree of cell dispersion, as described above, when a method of irradiating light from the light source 44 toward the flow cell 43 and detecting the transmitted light and / or scattered light with the detector 45 is employed, cell suspension This is particularly preferable because the degree of cell dispersion can be measured while the liquid is flowing.
- the method for measuring the degree of cell dispersion is not limited to this, and other methods may be adopted.
- an observation window may be provided in the circulation channel 6, an image (still image or moving image) may be taken with a microscope with a CCD camera, and the degree of cell dispersion may be calculated from the acquired image.
- Real-time processing is required to measure the cell suspension in a flowing state, but if such high-speed image processing is possible, it can be used as a cell dispersion measurement method instead of light intensity measurement. be able to.
- the material of the tube constituting the circulation flow path 6 is preferably one that does not affect the cells or is extremely small.
- An example of such a material is a medical silicone tube.
- the flow cell 43 may be made of glass, but if an inexpensive resin is used, it is more preferable to use a cell once passed through the cell because it is easy to make it disposable including the circulation channel 6.
- the cell state in which the cell clumps in the cell suspension are easily dispersed and the cells are uniformly dispersed by setting the second communication state by the communication state switching unit constituting the flow path module.
- a suspension can be obtained.
- FIG. 18 is an overall schematic configuration diagram of a cell number adjusting apparatus having a flow path module of Example 9 according to another embodiment of the present invention.
- the configuration of the flow channel module 1 shown in FIG. 7 in the first embodiment will be described as an example, but the configuration of the flow channel module 1 shown in FIG. 8 or the second to fifth embodiments has been described. The same applies to any of the configurations of the flow path module.
- the same components as those shown in the first embodiment are denoted by the same reference numerals, and the description overlapping with that in the first embodiment is omitted below.
- the cell number adjusting device 50 introduces a cell suspension in which the cell number concentration (the number of cells contained per unit amount of the cell suspension) containing cells at a high concentration is unknown.
- Inlet 56 dilution container 51 for adjusting the cell number concentration by adding a diluent to the introduced cell suspension, flow path module 1, circulation flow path 6 and, for example, a squeezing pump installed in circulation flow path 6 And the like, a flow cell 53 installed downstream of the pump 7 and in the circulation channel 6, a light source 54 for irradiating the cell suspension flowing through the flow cell 53, and a light source sandwiching the flow cell 53 54, a detector 55 installed on the opposite side of the flow cell 53, a buffer tank 57 installed in the circulation channel 6 on the downstream side of the flow cell 53, and an outlet 58 for discharging the cell suspension in which the number of cells is adjusted.
- a control unit 52 a control unit 52.
- the cell number adjusting device 50 takes in a cell suspension containing a high concentration of cells (number of cells contained per unit amount of cell suspension) from the inflow port 56, and concentration inside the cell suspension And a cell suspension containing cells at a desired cell number concentration lower than the cell number concentration in the cell suspension flowing in from the inflow port 56 is discharged from the outflow port 58. Between the inflow port 56 and the outflow port 58, a flow path system including the circulation flow path 6 is constructed. A pump 7 that is a liquid feed pump for causing the cell suspension in the flow path to flow is provided, and the control unit 52 controls at least the pump 7.
- the light intensity is measured as data relating to the cell number concentration per unit amount.
- Light is emitted from the light source 54 toward the flow cell 53, and the transmitted light and / or scattered light is detected by the detector 55.
- the light source 54, the flow cell 53, and the detector 55 constitute a cell number measuring device.
- the relationship between the intensity of transmitted light or scattered light detected by the detector 55 and the number of cells is separately determined in advance, and the relationship between the intensity of transmitted light or scattered light and the number of cells and the light intensity detected by the detector 55 are determined. Based on this, the cell number concentration is calculated.
- the intensity of transmitted light or scattered light is measured for each, and a calibration curve is obtained from the obtained results. Is required by creating The flow rate of the cell suspension passing through the flow cell 53 can be obtained based on the amount taken from the inlet 56 or based on the volume or cross-sectional area of the flow cell 53 and the liquid feeding speed of the pump 7. The amount of dilution required is determined based on the cell number concentration and the amount of cell suspension.
- the cell number concentration can be calculated with the cell suspension flowing.
- the detector 55 may continuously measure the light intensity continuously, or intermittently, that is, at intervals, preferably You may measure at regular intervals.
- another calculation method may be used for calculation of a cell number density
- a part of the inflow channel 4 is branched and connected to the branch channel 60, and a switching valve 61 is provided at the branch part.
- the switching valve 61 can switch between the branch channel 60 and the inflow channel 4.
- a pinch valve is preferably used as the switching valve 61.
- the pinch valve controls the flow by crushing (pinching) the flow path made of an elastic material from the outside, and does not directly contact the fluid, so the cell suspension and the pinch valve itself are not contaminated.
- the cell suspension can be controlled.
- the switching valve 61 has a function of switching between two flow paths, and can be realized by combining two pinch valves. However, a universal type valve that can alternately control the two flow paths simultaneously with one actuator is used. Also good.
- the control unit 52 controls the switching of the valve by controlling an actuator provided in the switching valve 61. The same applies to other switching valves described later.
- a diluent container 51 for storing a diluent is connected to the tip of the branch channel 60.
- the control unit 52 controls at least the pump 7 and preferably also the switching valve 61, adds a diluent to the cell suspension taken in according to the detection result of the detector 55, and further adds the cell suspension.
- the diluted solution is sufficiently stirred so that the cell number concentration is uniform.
- the control unit 52 drives the pump 7 in a state where the switching valve 61 closes the branch channel 60 and selects the inflow channel 4, and takes in the cell suspension stock solution from the inflow port 56.
- the taken-in cell suspension is directly transferred to the flow cell 53 via the flow path module 1.
- the communication state switching unit 3 configuring the flow path module 1 is in the second communication state.
- the control unit 52 calculates the cell number concentration from the measurement result, compares it with a predetermined target value, and determines the amount of the diluted solution that is necessary in consideration of the amount of the stock solution taken in.
- the control unit 52 switches the switching valve 61 to a state in which the branch channel 60 side is selected, drives the pump 7 for a certain time, and supplies the diluent from the diluent container 51 via the channel module 1. It takes in in the circulation flow path 6.
- the circulation channel 6 is in a state where two liquids, a cell suspension having a high cell number concentration before adjustment and a diluting liquid, exist unevenly.
- the controller 52 mixes the two liquids by driving the pump 7.
- the circulation channel 6 has a sufficient space for holding the cell suspension and the diluted solution, including a space for the movement.
- the measured value of the light intensity measurement is initially large because the cell number concentration in the circulation flow path 6 is non-uniform, but the fluctuation is large, but as the pump 7 is driven, the cell number concentration gradually becomes uniform and varies.
- the width becomes smaller and eventually converges to a target value, that is, a light intensity value corresponding to a predetermined cell number concentration. Therefore, when the temporal change in the measured value of the light intensity measurement falls within the range of the predetermined value (target value ⁇ ⁇ ), preferably at the time when the change disappears, the control unit 52 determines the branch member (flexible branch). Part) It is judged that the liquid in 2 has become uniform. If the converged value is different from the target value, the control unit 52 may repeat the dilution process described above. The cell suspension having a desired cell number concentration by the dilution process is discharged from the outlet 58 by driving the pump 7.
- the cross-sectional area of the circulation channel 6 and the like is small relative to the amount of cell suspension to be handled, it takes time to move in the channel when repeatedly moving for mixing, and the cell is burdened. Therefore, at least the cross-sectional area of the circulation channel 6 through which the cell suspension flows, more preferably the flow cell 53, has a sufficient size in consideration of the size of the cell to be handled and the amount of the cell suspension to be taken up. Preferably it is.
- the amount of the cell suspension to be taken is in the range of 1 mL to 1000 mL, it is preferable to use a tube having a diameter of about 1 to 10 mm as the tube constituting the circulation channel 6, and the flow cell 53 is 1 to 10 mm square. Are preferably used.
- the material of the tube constituting the circulation flow path 6 is preferably one that does not affect the cells or is extremely small.
- An example of such a material is a medical silicone tube.
- the flow cell 53 may be made of glass, but if an inexpensive resin is used, it is more preferable that the cell once passed through is easily disposable including the circulation flow path 6.
- the method for measuring the cell number concentration As a method for measuring the cell number concentration, as described above, when a method of irradiating light from the light source 54 toward the flow cell 53 and detecting the transmitted light and / or scattered light with the detector 55 is adopted, This is particularly preferable because the cell number concentration can be measured in a fluidized state.
- the method for measuring the cell number concentration is not limited to this, and other methods may be adopted.
- an observation window may be provided in the circulation flow path 6
- an image still image or moving image
- the number of cells may be calculated from the image.
- Real-time processing is required to measure the cell suspension in a flowing state, but if such high-speed image processing is possible, it can be used as a cell number concentration measurement method instead of light intensity measurement. be able to.
- the cell number adjustment apparatus 50 of a present Example not only dilutes a cell suspension by adding a diluent, but also a cell suspension. It may be used as a device for simply stirring. If the cell dispersion device 40 and the cell number adjustment device 50 are connected, the detached cells can be dispersed, and the number of cells can be adjusted and replated, that is, subculture can be performed.
- a branch channel and a diluent bag connected to the branch channel are further provided in the channel of the cell dispersion device 40, and the cell suspension concentration is based on the light intensity data detected by the detector 45 constituting the cell dispersion degree measuring device.
- the cell number adjusting device 50 can be omitted by adding a configuration that takes in a necessary amount of diluent from the diluent bag.
- this invention is not limited to the above-mentioned Example, Various modifications are included.
- the above-described embodiments have been described in detail for easy understanding of the present invention, and are not necessarily limited to those having all the configurations described.
- a part of the configuration of one embodiment can be replaced with the configuration of another embodiment, and the configuration of another embodiment can be added to the configuration of one embodiment.
- Buffer tank 27a, 47a, 57a ... Tank housing, 27b, 47b, 57b ... Inflow port, 27c, 47c, 57c ... Outflow port, 27d, 47d, 57d ... Air discharge Port, 28, 49, 59, 61 ... Switching valve, 30 ... Turbidimeter, 31, 43, 53 ... Flow cell, 32, 44, 54 ... Light source, 33, 45, 55 ... Detector, 34, 46, 56 ... Inlet, 35, 48, 58 ... Outlet, 40 ... Cell dispersion device, 41 ... Orifice, 42, 52 ... Control unit, 50 ... Cell number adjusting device, 51 ... Diluent container, 60 ... Branching channel
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Abstract
Description
また、特許文献2には、透析治療装置が開示され、複数の中空糸膜を有し血液を浄化するダイアナライザの血液導入ポートに、四方弁を介して接続可能とされる動脈側血液回路及び動脈側ドリップチャンバを有する構成が開示されている。上記四方弁内に2つの流路が形成され、血液ポンプを正転させる場合、四方弁により、動脈側血液回路、動脈側ドリップチャンバ、血液導入ポートの順に連通させ、患者の血液をダイアナライザへ導入する。また、血液ポンプを逆転させる場合、四方弁により、血液導入ポート、動脈側ドリップチャンバ、動脈側血液回路の順に連通させ、透析液を患者の動脈へ返送する構成が記載されている。また、更に、特許文献2では、四方弁を可撓性部材から成る袋体とクランプ部材で構成し、上記血液ポンプの正転及び逆転に応じて、上記袋体をクランプするクランプ部材の方向を切り替える構成も開示されている。
また、特許文献2の構成では、四方弁を回転させ、四方弁内の2つの流路を正確に位置決めしなければならない。また、クランプ部材と可撓性部材から成る袋体にて四方弁を構成する場合では、クランプ部材の開閉動作に加え、クランプ部材の向きを変更する動作が必須であるため、液置換を容易に実現することが困難となる。
また、本明細書において、「液置換」とは、後述する循環流路内に、例えば、細胞培養液等の液体を、気泡混入を防止しつつ充填する、或いは、異種の液体を循環流路内において入れ替える動作も含むものである。
以下、図面を用いて本発明の実施例について説明する。
分岐部材(可撓性分岐部)2は、相互に連通する4本の分岐流路、すなわち、流入流路4の端部と接続される第1の分岐流路2a、流出流路5の端部と接続される第2の分岐流路2b、循環流路6の入側端部6aと接続される第3の分岐流路2c、及び、循環流路6の出側端部6bと接続される第4の分岐流路2dを備える。図1に示す例では、分岐部材2を構成する第1の分岐流路2a~第4の分岐流路2dのうち、隣り合う2つの分岐流路が水平面内において直交するよう配される。流入流路4と接続される第1の分岐流路2aと循環流路6の出側端部6bと接続される第4の分岐流路2dとが対向しつつ連通する。また、流出流路5と接続される第2の分岐流路2bと循環流路6の入側端部6aと接続される第3の分岐流路2cとが対向しつつ連通する。
分岐部材(可撓性分岐部)2は、可撓膜(可撓性シート)から形成され、詳細後述する連通状態切替え部3を構成するピンチ部材3aと支持部材3bの間に配され、押圧部材として機能するピンチ部材3aの押圧力により容易に変形可能に構成されている。連通状態切替え部3は、一方向に移動するピンチ部材(押圧部材)3aと静止状態を維持する支持部材3bを備え、第1の分岐流路2a及び第2の分岐流路2bを挟むよう配される一組のピンチ部材3aと支持部材3bが配される。また、第1の分岐流路2aと第2の分岐流路2bが接合する角部と、第3の分岐流路2c及び第4の分岐流路2dとが接合する角部にわたり、分岐部材2の中心を通る平面視対角線状に他の一組のピンチ部材3aと支持部材3bが配される。
図2に示すように、分岐部材(可撓性分岐部)2は、2枚の可撓膜(可撓性シート)を合わせ、内部に相互に連通する第1の分岐流路2a、第2の分岐流路2b、第3の分岐流路2c及び第4の分岐流路2dを備える。これら各分岐流路の外側の側部は、接合部2eにて接合され、各分岐流路の横断面は、円形若しくは楕円形に形成される。なお、各分岐流路の横断面は、円形又は楕円形に限られるのではなく、矩形あるいは多角形状であっても良い。この場合、角部を丸めた形状とすることが望ましい。接合部2eの接合法としては、例えば、超音波溶着や接着等が用いられる。なお、分岐部材(可撓性分岐部)2に、各分岐流路を予め接合しても良い。すなわち、第1の分岐流路2aに流入流路4を、第2の分岐流路2bに流出流路5を、第3の分岐流路2cに循環流路6の入側端部6aを、また、第4の分岐流路2dに循環流路6の出側端部6bを挿入し接合しても良い。図2では、流入流路4、流出流路5、循環流路6の入側端部6a、及び循環流路6の出側端部6bが、予め分岐部材(可撓性分岐部)2に接合されている例を示している。なお、これに代えて、接続部品を介して、分岐部材2を構成する各分岐流路と、上述の流入流路4等をそれぞれ接続する構成としても良い。
次に、連通状態切替え部3の構成について説明する。図4は、連通状態切替え部3の概略構成図である。図4に示すように、連通状態切替え部3は、一方向に移動するピンチ部材(押圧部材)3a、静止状態にある支持部材3b、ピンチ部材3aの一方の端部に固定される可動鉄心3c、一端が可動鉄心3cの下面に接続され他端が固定鉄心3gに接続されるばね3e、コイル3f、及び支持部材3bの一方の端部を固定すると共に可動鉄心3c、ばね3e並びにコイル3fを収容する筐体3dを備える。押圧部材として機能するピンチ部材3aは、可動鉄心3cの動作と共に一方向に移動する。ピンチ部材3a及び可動鉄心3cを合わせて、以下、アクチュエータと称する。支持部材3bは、一端が筐体3dの上面に固定され、常時静止状態を維持する。支持部材3bは、筐体3dの上面より鉛直方向上方へと立設する立設部、立設部の上端部にて屈曲し水平方向へ延伸するノーマルクローズ側部材(NC側部材)3b1、及びNC側部材3b1より所定の間隔にて下方に位置し、立設部より水平方向へ延伸するノーマルオープン側部材(NO側部材)3b2から構成される。ここで、ピンチ部材3a及び支持部材3bは、剛性を有するものであれば良く、例えば、ステンレス鋼、鉄、或いは樹脂にて形成される。分岐部材(可撓性分岐部)2は、これら支持部材3bとピンチ部材3aの間に挿通され設置される。なお、図4では説明の便宜上、ピンチ部材3a及び支持部材3bの形状を簡略化し示している。
また、図4に示すばね3eに代えてロッドを配し、コイル3fに通電する電流の方向を切り替えることにより、アクチュエータが上下動する構成としても良い。
図5に示すギャップΔGを、分岐部材(可撓性分岐部)2に設けられる分岐流路の外径と略同一とした場合における、連通状態切替え部3への分岐部(可撓性分岐部)2の設置は例えば以下にて行う。図4に示すコイル3fが非通電の状態にて、ピンチ部材(押圧部材)3a1を構成する第2押圧部3a12と支持部材3b’を構成するNO側部材3b2’との間に、分岐部材(可撓性分岐部)2の第1の分岐流路2aを挿入すると共に、第3押圧部3a13とNO側部材3b2’との間に第2の分岐流路2bを挿入する。その後コイル3fに通電し、ピンチ部材(押圧部材)3a1を下方へ移動させ、第2押圧部3a12とNO側部材3b2’にて第1の分岐流路2aを押し潰す(ピンチする)と共に、第3押圧部3a13とNO側部材3b2’にて第2の分岐流路2bを押し潰す。これにより、支持部材3b’を構成するNC側部材3b1とピンチ部材(押圧部材)3a1を構成する第1押圧部3a11との間にギャップΔGが形成される。ここで、NC側部材3b1と第1押圧部3a11との間に、第3の分岐流路2c及び第4の分岐流路2dを挿入する。ことき、第3の分岐流路2cと第4の分岐流路2dとが接合する角部の下面が第1押圧部3a11上に、また、第3の分岐流路2cと第4の分岐流路2dとが接合する角部の上面がNC側部材3b1の直下に位置するよう配される。同様に、第1の分岐流路2aと第2の分岐流路2bとが接合する角部の下面が第1押圧部3a11上に、また、第1の分岐流路2aと第2の分岐流路2bとが接合する角部の上面がNC側部材3b1の直下に位置するよう配される。以上にて、分岐部材(可撓性分岐部)2の連通状態切替え部3への設置が完了する。
図6に示すギャップΔGを、分岐部材(可撓性分岐部)2に設けられる分岐流路の外径と略同一とした場合における、連通状態切替え部3への分岐部(可撓性分岐部)2の設置について以下に説明する。なお、ここでは、分岐部材(可撓性分岐部)2内に設けられる4本の分岐流路が、第1の分岐流路2aと第2の分岐流路2bとが対向しつつ連通するよう配され、第3の分岐流路2cと第4の分岐流路2dとが対向しつつ連通するよう配される場合を想定する。図4に示すコイル3fが非通電の状態にて、ピンチ部材(押圧部材)3a2を構成する第2押圧部3a22と支持部材3b”を構成する第1のNO側部材3b21との間に、分岐部材(可撓性分岐部)2の第2の分岐流路2bを挿入すると共に、第3押圧部3a23と第2のNO側部材3b22との間に第1の分岐流路2aを挿入する。その後コイル3fに通電し、ピンチ部材(押圧部材)3a2を下方へ移動させ、第2押圧部3a22と第1のNO側部材3b21にて第2の分岐流路2bを押し潰す(ピンチする)と共に、第3押圧部3a23と第2のNO側部材3b22にて第1の分岐流路2aを押し潰す。これにより、支持部材3b”を構成するNC側部材3b11とピンチ部材(押圧部材)3a2を構成する第1押圧部3a21との間にギャップΔGが形成される。ここで、NC側部材3b11と第1押圧部3a21との間に、第3の分岐流路2c及び第4の分岐流路2dを挿入する。ことき、第3の分岐流路2cと第4の分岐流路2dとが接合する角部の下面が第1押圧部3a21上に、また、第3の分岐流路2cと第4の分岐流路2dとが接合する角部の上面がNC側部材3b11の直下に位置するよう配される。同様に、第1の分岐流路2aと第2の分岐流路2bとが接合する角部の下面が第1押圧部3a21上に、また、第1の分岐流路2aと第2の分岐流路2bとが接合する角部の上面がNC側部材3b11の直下に位置するよう配される。以上にて、分岐部材(可撓性分岐部)2の連通状態切替え部3への設置が完了する。
図7は、図5に示す連通状態切替え部を有する流路モジュールを含む全体概略構成図である。図7に示すように、流路モジュール1は、分岐部材(可撓性分岐部)2及び図5に示した連通状態切替え部3を備える。
分岐部材(可撓性分岐部)2は、流入流路4の端部と接続される第1の分岐流路2a、流出流路5の端部と接続される第2の分岐流路2b、循環流路6の入側端部6aと接続される第3の分岐流路2c、及び、循環流路6の出側端部6bと接続される第4の分岐流路2dを備える。第1の分岐流路2aと第4の分岐流路2dとが対向しつつ連通され、第2の分岐流路2bと第3の分岐流路2cとが対向しつつ連通されている。循環流路6の入側端部6aと接続される第3の分岐流路2cと、循環流路6の出側端部6bと接続される第4の分岐流路2dとが隣り合うよう配される。
このように、連通状態切替え部3により、第2の連通状態としポンプ7を駆動し、所定時間経過後に第1の連通状態に切り替えることで、循環流路6内の完全な液置換が実現できる。
なお、液置換時の連通状態切替え部3による第2の連通状態から第1の連通状態への切り替え動作については、上述の図7と同様ゆえ説明を省略する。
ピンチ部材8a及び支持部材8bは、剛性を有するものであれば良く、例えば、ステンレス鋼、鉄、或いは樹脂にて形成される。
また、第1ローラ9a1~第3ローラ9a3を回転可能に支持する、連結部材9bを構成する2辺の線状又は棒状部の両端部を連結し、相互に所定の間隔にて離間し対向する他の2辺の線状或いは棒状部を直線状にて形成したが、必ずしもこれに限られるものではない。例えは、上記他の2辺を円弧状にするなど、第1ローラ9a1~第3ローラ9a3を回転可能に支持する2辺の線状又は棒状部の両端部を連結する構造であれはいずれの形状としても良い。
その他の構成要素は実施例1と同様であるため、以下では実施例1と重複する説明を省略する。
また、循環流路内にバッファタンクを設置することにより、所望の培養量を得ることが可能となる。
また、仮に低濁度を有する液体の場合或は環境光等の外乱ノイズにより、一度の計測にて濁度を測定できない場合であっても、連通状態切替え部にて第1の連通状態に切り替え当該液体を、循環流路内を循環させることで、確実に濁度を計測することが可能となる。
細胞分散装置40と細胞数調整装置50を接続すれば、剥離した細胞を分散し、細胞数を調整した上で再播種する、すなわち継代培養が可能である。また、例えば細胞分散装置40の流路に分岐流路とそこに繋がる希釈液バッグをさらに設け、細胞分散度測定器を構成する検出器45が検出した光強度データに基づいて細胞懸濁液濃度を判断し、必要な量の希釈液を希釈液バッグから取り込むような構成を追加することにより、細胞数調整装置50は省略することもできる。
Claims (15)
- 流体の流入流路の端部と接続される第1の分岐流路と、流出流路の端部と接続される第2の分岐流路と、循環流路の入側端部と接続される第3の分岐流路と、前記循環流路の出側端部と接続される第4の分岐流路を備え、前記各分岐流路間を連通可能とする可撓性分岐部と、
前記複数の分岐流路のうち所望の分岐流路を閉塞又は開放する開閉部材を有し、前記開閉部材を一方向へ移動し前記所望の分岐流路を押圧し閉塞することで、前記第3の分岐流路と第4の分岐流路が連通する第1の連通状態、及び、前記第1の分岐流路と前記第3の分岐流路が連通し且つ前記第2の分岐流路と前記第4の分岐流路が連通する第2の連通状態を切り替える連通状態切替え部と、を備えることを特徴とする流路モジュール。 - 請求項1に記載の流路モジュールにおいて、
前記開閉部材は、前記可撓性分岐部に対し直交する方向に移動し、前記第1の連通状態と第2の連通状態を切り替えることを特徴とする流路モジュール - 請求項1に記載の流路モジュールにおいて、
前記開閉部材は、前記可撓性分岐部に対し平行な方向に移動し、前記第1の連通状態と第2の連通状態を切り替えることを特徴とする流路モジュール。 - 請求項1に記載の流路モジュールにおいて、
前記開閉部材は、静止状態を維持する支持部材と、前記可撓性分岐部を挟み前記支持部材と反対側に配される押圧部材を備え、
前記押圧部材を一方向に移動し前記所望の分岐流路を押圧し閉塞することにより、前記第1の連通状態と第2の連通状態を切り替えることを特徴とする流路モジュール。 - 請求項4に記載の流路モジュールにおいて、
前記支持部材は、前記可撓性分岐部の下面に配され、平面視十字状又はT字状の形状を有し、
前記押圧部材は、垂直投影面内においてT字状の形状を有し、前記支持部材と対向しつつ一方向へ延伸する第1押圧部と、前記第1押圧部に対し垂直方向へ延伸する第2押圧部を備え、
前記2押圧部は、前記第1押圧部との連結部より上方へと傾斜し所定の位置にて屈曲し所定の角度にて下方へ傾斜する横断面形状を有すると共に、前記連結部にて前記支持部材に設けられたヒンジと連結され、前記ヒンジを支点として、円弧状に回動することを特徴とする流路モジュール。 - 請求項3に記載の流路モジュールにおいて、
前記開閉部材は、前記可撓性分岐部を載置する平板状の支持部材と、前記可撓性分岐部上に位置し前記可撓性分岐部に押し付け荷重を付与する複数のローラを回転可能に支持する平面視矩形状の連結部材と、前記連結部材が前記可撓性分岐部材に対し平行な方向へ移動すると共に、前記複数のローラは前記連結部材が移動する方向に対し直交するよう対向配置される2辺に回転可能に支持されることを特徴とする流路モジュール。 - 請求項6に記載の流路モジュールにおいて、
前記可撓性分岐部は、平面視四角形状をなし、一の側面より等間隔にて前記可撓性分岐部の中央部側へ向かい延伸する3本の流路壁により、前記第1の分岐流路、前記第3の分岐流路、前記第4の分岐流路、及び前記2の分岐流路の順に分岐流路が画成され、
前記連結部材のうち前記流路壁と平行であって対向する2辺にそれぞれ前記ローラが回転可能に支持されることを特徴とする流路モジュール。 - 請求項2に記載の流路モジュールにおいて、
前記可撓性分岐部は、前記第3の分岐流路及び前記第4の分岐流路が相互に対向しつつ連通し直線状に配されると共に、前記第1の分岐流路及び前記第2の分岐流路が、前記直線状に配される前記第3の分岐流路及び前記第4の分岐流路に直交又は所定の角度にて連通することを特徴とする流路モジュール。 - 請求項8に記載の流路モジュールにおいて、
前記開閉部材は、静止状態を維持する支持部材と、前記可撓性分岐部に対し直交する方向へ移動する押圧部材を備え、
前記支持部材は、鉛直方向に延伸する立設部と、当該立設部の上端部にて屈曲し水平方向へ延伸する第1支持部と、前記第1支持部より所定の間隔にて下方に位置すると共に前記立設部より水平方向に延伸する第2支持部を有し、前記第1支持部及び前記第2支持部は垂直投影面内において相互に直交するよう配され、
前記押圧部材は、鉛直方向に延伸する立設部と、当該立設部の上端部に位置し前記第1支持部に対向するよう水平方向へ延伸する第1押圧部と、前記第1押圧部の一方端側に配され前記第2支持部と対向するよう水平方向に延伸する第2押圧部と、前記第1押圧部の一方端側に配され前記第2支持部と対向するよう水平方向に延伸する第3押圧部を有することを特徴とする流路モジュール。 - 細胞懸濁液又は培地を通流する流入流路と、
前記細胞懸濁液又は培地を循環する循環流路と、
前記循環流路に設置されるポンプと、
前記ポンプの下流側であって前記循環流路に設置される培養容器と、
流出流路に接続される回収バックと、
前記流入流路及び前記循環流路並びに前記流出流路に接続される流路モジュールを備え、
前記流路モジュールは、
前記流入流路の端部と接続される第1の分岐流路と、前記流出流路の端部と接続される第2の分岐流路と、前記循環流路の入側端部と接続される第3の分岐流路と、前記循環流路の出側端部と接続される第4の分岐流路を有し、前記各分岐流路間を連通可能とする可撓性分岐部と、
前記複数の分岐流路のうち所望の分岐流路を閉塞又は開放する開閉部材を有し、前記開閉部材を一方向へ移動し前記所望の分岐流路を押圧し閉塞することで、前記第3の分岐流路と第4の分岐流路が連通する第1の連通状態、及び、前記第1の分岐流路と前記第3の分岐流路が連通し且つ前記第2の分岐流路と前記第4の分岐流路が連通する第2の連通状態を切り替える連通状態切替え部を有することを特徴とする細胞培養装置。 - 請求項10に記載の細胞培養装置において、
前記培養容器の下流側であって、前記循環流路に設置されるバッファタンクを備え、
前記バッファタンクは、前記循環流路内を通流する細胞懸濁液又は培地を導入する流入ポートと、前記バッファタンク内に収容される細胞懸濁液又は培地を前記循環流路へ送液する流出ポートと、前記バッファタンク内の空気を前記循環流路へ排出する空気排出ポートと、前記流出ポート及び前記空気排出ポートのうちいずれか一方を選択的に切り替える切換え弁を有することを特徴とする細胞培養装置。 - 請求項11に記載の細胞培養装置において、
前記開閉部材は、前記可撓性分岐部に対し直交する方向に移動し、前記第1の連通状態と第2の連通状態を切り替えることを特徴とする細胞培養装置。 - 請求項11に記載の細胞培養装置において、
前記開閉部材は、前記可撓性分岐部に対し平行な方向に移動し、前記第1の連通状態と第2の連通状態を切り替えることを特徴とする細胞培養装置。 - 請求項11に記載の細胞培養装置において、
前記開閉部材は、静止状態を維持する支持部材と、前記可撓性分岐部を挟み前記支持部材と反対側に配される押圧部材を備え、
前記押圧部材を一方向に移動し前記所望の分岐流路を押圧し閉塞することにより、前記第1の連通状態と第2の連通状態を切り替えることを特徴とする細胞培養装置。 - 請求項13に記載の細胞培養装置において、
前記支持部材は、前記可撓性分岐部の下面に配され、平面視十字状又はT字状の形状を有し、
前記押圧部材は、垂直投影面内においてT字状の形状を有し、前記支持部材と対向しつつ一方向へ延伸する第1押圧部と、前記第1押圧部に対し垂直方向へ延伸する第2押圧部を備え、
前記2押圧部は、前記第1押圧部との連結部より上方へと傾斜し所定の位置にて屈曲し所定の角度にて下方へ傾斜する横断面形状を有すると共に、前記連結部にて前記支持部材に設けられたヒンジと連結され、前記ヒンジを支点として、円弧状に回動することを特徴とする細胞培養装置。
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WO2020009017A1 (ja) * | 2018-07-05 | 2020-01-09 | 富士フイルム株式会社 | 細胞培養装置及び撹拌方法 |
WO2020017407A1 (ja) * | 2018-07-17 | 2020-01-23 | 国立大学法人神戸大学 | サンプリング装置 |
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