阅读说明：本技术 切换阀、及具备切换阀的吸入喷出装置 (Switching valve and suction/discharge device provided with switching valve ) 是由 宗像光良 谷冈笃吉 于 2016-09-08 设计创作，主要内容包括：以往的吸入喷出装置具备的切换阀在主体内部配置驱动部,且试样在切换阀主体内部流通,因此,不能进行高压灭菌器灭菌等处理,不能完全排除杂菌等污染原因。本发明的切换阀通过设为从外部按压试样流通的管而将管内的流通关闭的机构,成为杂菌等污染原因不会传播至切换阀的构造。进而,本发明的吸入喷出装置上设置的管和注射泵为即使发生污染也能够容易地进行更换的组件。(Since the switching valve of the conventional suction/discharge device has a drive unit disposed in the main body and the sample flows through the switching valve main body, it is impossible to perform a process such as autoclave sterilization, and the cause of contamination such as contamination cannot be completely eliminated. The switching valve of the present invention is configured to be a mechanism for closing the flow in the tube by pressing the tube through which the sample flows from the outside, and thereby, a contamination cause such as a contamination is not transmitted to the switching valve. Further, the tube and the syringe pump provided in the suction/discharge device of the present invention are components that can be easily replaced even if contamination occurs.)

1. A switching valve constituting a suction/discharge device, the suction/discharge device comprising: a tube assembly having a pair of tubes; a pair of switching valves for holding the pair of tubes of the tube assembly between a pair of pressing members and a pair of rollers, and pressing the pair of tubes to selectively close one or both of the tubes or open both of the tubes; and a syringe pump connected to the tube assembly, the switching valve including:

a rotor including the pair of rollers rotatably attached to both ends;

a rotor driving unit that rotationally drives the rotor to revolve the roller; and

a pair of pressing members provided opposite to each other at positions outside the revolution orbit of the pair of rollers that revolve by the rotation of the rotor, the pressing members being engaged with the rollers and having wall surfaces with the same curvature as that of concentric circles outside the revolution orbit,

a gap between each of the pressing members and the revolution path of each of the rollers is narrow, and when the pair of tubes of the tube assembly are arranged between the revolution path of each of the rollers and the pair of pressing members, the rollers are stopped at predetermined positions of the pressing members on the revolution path, so that pressing regions are formed in which the corresponding rollers and the pressing members cooperate to press and close either one or both of the pair of tubes,

the pressing area includes a first area for closing both the pair of tubes and a second area for closing only one of the pair of tubes,

further, the roller includes a third region that opens the flow of both the pair of tubes in a region other than the pressing region on the revolution path of the roller,

the pair of rollers includes the revolution orbit which can move to the second region without passing through the third region even when moving from the first region to the second region to close any one of the pair of tubes.

2. The switching valve according to claim 1,

the pair of pressing members are disposed opposite to each other outside the revolution path so that the pair of pipes are disposed in parallel when the pair of pipes of the pipe assembly are disposed between the pair of pressing members and the revolution path of the pair of rollers,

the rotation center axis of the rotor is arranged at a position deviated from a straight line connecting the rotation centers of the pair of rollers,

the pressing region is formed such that: the pressing member is configured to extend along the wall surface of the pressing member with a position of an intersection of a straight line passing through a rotation center of the rotor and extending in a direction perpendicular to the pipe and the pressing member as a center.

3. The switching valve according to claim 1,

the pair of pressing members are disposed opposite to each other on the outer side of the revolution orbit so that the pair of pipes are symmetrically disposed at a predetermined acute angle from each other with respect to the central axis when the pair of pipes of the pipe assembly are disposed between the pair of pressing members and the revolution orbit of the pair of rollers,

the center axis is a straight line extending in a direction connecting an intersection of the pair of tubes disposed at the acute angle and a rotation center of the rotor,

the pressing member is disposed outside the pair of tubes symmetrically with respect to the central axis, and has the pressing region extending along the wall surface of the pressing member.

4. A tube assembly constituting a suction/discharge device, the suction/discharge device comprising: a tube assembly having a pair of tubes; a pair of switching valves for holding the pair of tubes of the tube assembly between a pair of pressing members and a pair of rollers, and pressing the pair of tubes to selectively close one or both of the tubes or open both of the tubes; and a syringe pump connected to the tube assembly, the tube assembly including:

a first pipe made of a flexible material capable of bending deformation, having an elastic force capable of deforming and restoring in a radial direction at least in a region pressed by the pressing member and the roller, and constituting the pair of pipes;

a second tube made of a flexible material capable of bending deformation, having an elastic force capable of deforming and restoring in a radial direction at least in a region pressed by the pressing member and the roller, and constituting the pair of tubes;

a first connection end portion provided at one end of the first pipe;

a second connection end portion provided at one end of the second pipe; and

a third connection end portion connecting opposite ends of the first connection end portion and the second connection end portion of the first pipe and the second pipe,

the pipe assembly is installed between the pressing member of the switching valve and the revolution orbit.

5. The tube assembly of claim 4,

the first tube and the second tube are made of a material that corresponds to a sterilization process.

6. The tube assembly of claim 5,

two connection portions of a hollow connector provided with three connection portions are connected to each of the opposite ends of the first connection end portion and the second connection end portion of each of the first tube and the second tube, and the other connection portion of the three connection portions of the connector is connected to the syringe pump via a third tube, and the connector is made of a material corresponding to a sterilization process.

7. A suction/discharge device is characterized by comprising:

a switching valve as claimed in any one of claims 1 to 3;

the tube assembly of claim 4 or 5, mounted to the switching valve;

a syringe pump to which the third connection end of the tube assembly is connected; and

a pump driving part which makes the piston part of the injection pump move forwards and backwards relative to the cylinder part,

the pump driving section cooperates with the rotor driving section to cause the sample to flow through the pair of tubes.

8. A medium replacement device is characterized in that,

the suction/discharge device according to claim 7.

9. A dispensing device is characterized in that,

the suction/discharge device according to claim 7.

10. An automatic culture system, comprising:

the medium replacement device of claim 8;

a culture apparatus that houses a container that houses a sample in a thermostatic chamber that is adjusted to a predetermined environment; and

and a transport mechanism that transports the container between the medium replacement device and the culture device.

11. An automatic culture system, comprising:

the medium replacement device of claim 8;

a dispensing apparatus according to claim 9;

a culture apparatus that houses a container that houses a sample in a thermostatic chamber that is adjusted to a predetermined environment; and

and a transport mechanism that transports the container between the medium replacement device and the culture device.

Technical Field

The present invention relates to a pump module mounted on a dispenser or a medium replacement device, and more particularly, to a pump module capable of supplying a liquid in an aseptic state and a suction/discharge module capable of being replaced suitably for the pump module. The present invention also relates to an automatic culture medium exchange device, a dispensing device, and an automatic culture system, each of which incorporates the pump module.

Background

A dispensing device is known as a device for transferring a liquid such as a sample or a reagent used for a test or analysis performed in the field of biotechnology. In addition, a medium exchange device is known as a device for exchanging a culture solution serving as a medium at a predetermined timing in a long-term cell culture performed in the field of regenerative medicine. These apparatuses are each provided with a suction/discharge device for sucking and discharging a liquid sample such as a cell suspension or a culture solution.

Here, a description will be given below of a suction/discharge device provided in a conventional dispensing device or a medium exchange device. In the dispensing device described in patent document 1, a tube pump PM that rotates a pressing roller by a motor and continuously presses a soft tube by the pressing roller to move a fluid in the tube in a predetermined direction is used as a pump for sucking and discharging a sample. Refer to fig. 1. By the operation of the tube pump PM, the sample stored in the storage container BT is sucked and discharged to the dispensing heads h1 and h 2. This enables the supply of the sample, which has been performed manually, to be completed in a short time. However, although the tube pump can continuously supply a large amount of samples, it is difficult to accurately discharge the samples. Further, since the pressing roller continuously presses the flexible tube, the flexible tube through which the fluid flows is deteriorated, and the accuracy of the discharge amount is deteriorated. Further, there is a problem that the inner wall of the tube is peeled off, and the sample is mixed with the sample.

In contrast, the suction/discharge device described in patent document 2 includes a syringe-type syringe pump 1 as a pump unit (each part is denoted by the reference numeral of patent document 2, and the same is applied to the following present paragraph). In the suction/discharge device, the following structure is adopted: the sample is sucked by pulling out the plunger 1a of the syringe pump 1 from the cylinder 1b by the pump driving unit 7, and the sample is discharged by pushing the plunger 1a into the cylinder 1 b. The direction of the liquid suction and discharge can be switched by the switching valve 13 that is driven to open and close by the valve opening and closing means 27. By switching the switching valve 13, the sample liquid in the sample container 9 can be sucked through the water filled in the tube 5 and discharged into the reaction tube 11. The operation of the pump driving unit 7 or the valve opening/closing unit 27 is electrically controlled by the control device 31, and a predetermined amount of liquid can be sucked into and discharged from a predetermined place according to a predetermined procedure.

Disclosure of Invention

Problems to be solved by the invention

The following problems occur when a correct amount of sample can be automatically sucked and ejected by the above-described comparison technique.

That is, even when the conventional pump is used, there is a problem that the sample is contaminated by dust generated from the switching valve itself provided to switch the direction of sucking and discharging the sample. The suction/discharge device is periodically cleaned with a sterilizing solution or treated with an autoclave to remove foreign bacteria and contaminants entering from the external environment. However, the switching valve cannot perform sterilization or autoclave treatment in a structure in which a flow path formed in the main body is passed through with a sample, and a valve body provided in the main body is electrically operated to switch the flow path. Therefore, there is also a problem that the foreign bacteria or dust remaining in the switching valve through which the sample flows adversely affects the next culture. Further, in the tube or the cylinder after the sterilization treatment, there is a problem that the contamination due to the adhesion of foreign bacteria or dust floating in the air adversely affects the cell culture when the tube or the cylinder is mounted again after the sterilization treatment.

The present invention has been made to solve the above-described problems, and an object of the present invention is to provide a switching valve capable of effectively preventing contamination of dust and bacteria, a suction/discharge device provided with the switching valve, a medium exchange device provided with the suction/discharge device, a dispensing device, and an automatic culture system provided with these devices. It is another object of the present invention to provide an inhalation/ejection module which is suitable for use in such an inhalation/ejection device and is aseptically packaged and easily replaceable.

Means for solving the problems

In order to solve the above problem, the present invention provides a switching valve including: a rotor including a pair of rollers rotatably attached to both ends; a rotor driving unit that rotationally drives the rotor; a pair of pressing members provided at positions outside the revolution orbit of the pair of rollers that revolve by the rotation of the rotor, the pressing members being operated in cooperation with the rollers; and a pair of pipes each disposed between the revolution orbit of each of the rollers and the pair of pressing members, wherein the pressing members are disposed such that a gap between the pressing members and the revolution orbit of each of the rollers is gradually narrowed, and a pressing region in which the corresponding roller and the pressing member press the pipe is formed by the revolution of the roller, and each of the pair of pipes is selectively closed and opened from the outside by the pair of rollers and the pair of pressing members. With the above configuration, the tube can be switched between open and closed without introducing a sample into the switching valve.

Further, the switching valve of the present invention is characterized in that the rotor is rotatably movable between a position where both the pair of pipes are closed, a position where only one of the pair of pipes is closed, and a position where both the pair of pipes are opened to flow. With the above configuration, the flow inside the pair of pipes can be closed and opened by one driving source.

Further, the switching valve of the present invention is characterized in that the rotational center axis of the rotor is disposed at a position deviated from a straight line connecting the rotational centers of the pair of rollers, and the pair of pressing members have the pressing regions which pass through the rotational center of the rotor and are symmetrical with respect to a straight line extending in the horizontal direction. With the above configuration, the rotor can easily close and open the internal flow of each tube with respect to a pair of tubes arranged in parallel with each other. Further, the switching valve of the present invention may be configured such that the rotational center axis of the rotor is disposed on a straight line connecting the rotational centers of the pair of rollers, and the pair of pressing members may have the pressing regions that pass through the rotational center of the rotor and are symmetrical with respect to a straight line extending in the vertical direction.

Further, the suction/discharge device of the present invention includes: the switching valve of the present invention; a syringe pump to which respective end portions of the pair of tubes are connected; and a pump driving unit that moves the piston unit of the syringe pump forward and backward relative to the cylinder unit, and cooperates with the rotor driving unit to circulate the sample inside the pair of tubes. With the above configuration, even when contamination of the sample occurs, the contaminated syringe pump and tube can be removed from the suction/discharge device and replaced with new ones, thereby facilitating removal of the contamination. When this replacement is performed, the switching valve and the pump driving unit do not directly contact the sample, and therefore contamination in the sample does not propagate.

The present invention also provides a suction/discharge module used in the suction/discharge device of the present invention, comprising the pair of pipes and the syringe pump to which one end of each of the pair of pipes is connected, and the suction/discharge module is attachable to the switching valve and aseptically packaged. With the above configuration, when the syringe pump and the tube are provided to the intake and discharge device, there is no need to perform operations such as sterilization and cleaning in advance. Further, since there is no need to adjust the length of the pipe in accordance with the size of the device to be installed, it is possible to prevent the contaminant floating in the atmosphere from entering the flow path by installing the pipe in the suction/discharge device quickly.

Further, the aspiration/ejection device of the present invention is used as a pump unit for supplying a medium in a medium exchange device, a pump unit for delivering a reagent such as water or a cell suspension by pressure in an aspiration/ejection dispensing device, and a switching valve, and thus, there is no possibility of contamination with bacteria and the like, and it is possible to perform culture and test with high accuracy.

Further, if an automatic culture system is constituted by a medium changer or dispenser on which the suction/discharge device of the present invention is mounted, a culture device that stores a container storing a sample in a thermostatic chamber adjusted to a predetermined environment, and a transport device that transports the container between the medium changer or dispenser and the culture device, it is possible to automatically culture the sample for a long period of time.

Effects of the invention

According to the switching valve of the present invention, since the flow of the sample can be controlled without causing the sample to flow into the main body, dust generated from the valve main body does not enter the sample. In addition, when the sample is contaminated with the foreign bacteria, the space in which the sample flows can be returned to a clean state only by a simple operation of sterilizing the tube in which the sample flows with an autoclave or sterilizing the tube with hydrogen peroxide gas, or disposing a new sterile tube by discarding the contaminated tube. This can omit the cleaning operation inside the on-off valve, and thus can reduce the burden on the operator.

In addition, according to the suction/discharge device of the present invention, the sample can be accurately supplied without flowing into the main body. Even when the sample is contaminated with the foreign bacteria, the space in which the sample is to be distributed can be returned to a clean state by a simple operation of sterilizing the tube and the syringe pump in which the sample is to be distributed by autoclaving or sterilizing the tube and the syringe pump by hydrogen peroxide gas, or disposing the contaminated tube and the syringe pump and providing a new sterile tube. This can omit the cleaning operation of the inside of the opening/closing valve or the pump, and thus can reduce the burden on the operator.

In addition, according to the inhalation/ejection module of the present invention, since the sterilization operation performed at the time of installation can be omitted, the burden on the operator can be reduced. Further, the possibility of bacteria and dust remaining after the cleaning operation can be eliminated.

Drawings

Fig. 1 is a diagram showing a suction/discharge device using a conventional tube pump.

Fig. 2 is a diagram showing a suction/discharge device using a conventional switching valve.

Fig. 3 is a perspective view showing an embodiment of the switching valve of the present invention.

Fig. 4 is a block diagram showing the configuration of the suction/discharge device 2 of the present invention.

Fig. 5 is a diagram showing an operation of the rotor 4 provided in the switching valve 3 according to the present invention.

Fig. 6 is a front view and a side view showing the inhalation/ejection device 2 of the present invention, and a part of the device is shown in cross section.

Fig. 7 is a diagram showing an operation of the rotor 4 provided in the switching valve 3 according to the present invention.

Fig. 8 is a diagram showing an operation of the rotor 4 provided in the switching valve 3 according to the present invention.

Fig. 9 is a diagram showing an operation of the rotor 4 provided in the switching valve 3 of the present invention.

Fig. 10 is a diagram showing a switching valve 3' according to a second embodiment of the present invention.

FIG. 11 is a perspective view showing one embodiment of a medium replacement device according to the present invention.

FIG. 12 is an explanatory view showing the operation of supplying a medium by the medium replacement apparatus of the present invention.

FIG. 13 is a view showing the operation of a tilting mechanism provided in the medium exchange device of the present invention.

Fig. 14 is a perspective view showing one embodiment of a dispensing device of the present invention.

Fig. 15 is a cross-sectional view showing a state in a pipette tip when a sample is aspirated by the dispensing device of the present invention.

FIG. 16 is a sectional view showing the outline of the automatic culture system of the present invention.

Detailed Description

Hereinafter, embodiments of the present invention will be described with reference to the drawings. Fig. 3 is a perspective view showing the switching valve 3 of the present invention. Fig. 4 is a block diagram showing the configuration of the suction/discharge device 2 of the present invention. Fig. 5 is a diagram showing the operation of the rotor 4 provided in the switching valve 3 according to the present embodiment. A rotor 4 is disposed in the central portion of the main body of the switching valve 3, and rollers 6a and 6b are rotatably attached to the left and right of the rotor 4. Further, pipes 8 and 9 are disposed so as to pass through the vicinity of both side surfaces of the rotor 4. The switching valve 3 is configured to regulate the flow of the sample inside the tube by rotating the rotor 4 in a predetermined direction and pressing the tubes 8 and 9 with the rollers 6a and 6 b. A shaft 10 is fixed to a central portion of the rotor 4. The shaft 10 penetrates the substrate 11 and is connected to a motor 12 fixed to a surface of the substrate 11 opposite to the surface on which the rotor 4 is disposed. The motor 12 provided in the suction/discharge device 2 of the present invention is a stepping motor capable of accurately controlling the rotation direction and the rotation angle. The operation of the motor 12 is controlled by the rotor control unit 14, and the motor 12 is operated to a predetermined rotational direction and a predetermined rotational position by a signal from the rotor control unit 14. The motor 12 and the rotor control unit 14 constitute a rotor driving unit that rotates the rotor 4 to a predetermined angle. In the figure, the pipes 8 and 9 disposed in the switching valve 3 of the present embodiment are disposed in parallel to each other in the vertical direction.

The rotor 4 of the present embodiment is formed in a substantially triangular shape in front, and cylindrical rollers 6a and 6b are rotatably fixed to the rotor 4 via shafts 16a and 16b at both ends of the main body of the rotor 4. The rotor 4 is rotatable by a motor 12 around a central axis C of the shaft 10. By the rotation operation of the rotor 4, the rollers 6a and 6b revolve on a circular orbit a1 (see fig. 5) having the central axis C of the shaft 10 as the rotation center. The pressing members 17a and 17b are disposed at bilaterally symmetrical positions outside the revolution orbit a1 of the rollers 6a and 6 b. The surfaces (inner surfaces) of the pressing members 17a and 17b facing the rotor 4 are curved along an arc a2 having a radius larger than the revolution orbit a1 of the rollers 6a and 6 b. The inner surfaces formed along the arcs a2 of the pressing members 17a and 17b and the rollers 6a and 6b press the tubes 8 and 9 in cooperation with each other, thereby closing the flow inside the tubes 8 and 9. This closing area is referred to as a pressing area in this specification. The pressing region of the present embodiment is formed along the arc a2, and has a shape symmetrical to the straight line L3 extending in the horizontal direction with respect to the center axis C passing through the shaft 10. The radius of the arc a2 of the pressing area is preferably a radius obtained by adding the thickness of the pipes 8 and 9 to the radius of the arc a1, which is the path described by the rollers 6a and 6 b. Further, in the present embodiment, the pressing region has a shape that is bilaterally symmetric with respect to a straight line extending in the vertical direction through the central axis C of the shaft 10. By providing the pressing regions in this way, the rotor 4 is rotated in a predetermined direction by the operation of the motor 12, and accordingly, the rollers 6a and 6b also perform the revolution operation, and the rollers 6a and 6b approach or separate from the corresponding pressing members 17a and 17 b. By the revolution of the rollers, the pipes 8 and 9 disposed between the rotatably mounted rollers 6a and 6b and the pressing members 17a and 17b are pinched or opened. This enables the flow of the sample in the tubes 8 and 9 to be controlled. Further, as for the members constituting the switching valve 3 of the present invention, various sterilization treatments such as autoclave sterilization and hydrogen peroxide gas sterilization are considered, and it is desirable to use stainless steel or resin having excellent heat resistance and chemical resistance such as PTFE and polyimide resin.

The rollers 6a and 6b are rotatably mounted around the central axes C of the shafts 16a and 16b, respectively. The rotation center axis C of the rotor 4 is disposed at a position eccentric from the midpoint of a line L1 connecting the rotation centers of the rollers 6a and 6 b. In the example shown in fig. 5, the rotation center C of the rotor 4 is arranged on a right-angle bisector of a line connecting the rotation centers of the rollers 6a and 6 b. Thus, by rotating the rotor 4 to a predetermined rotational position, the flow of the sample in one tube 8 of the tubes 8 and 9 arranged in parallel to each other can be restricted, and the flow of the sample in the other tube 9 can be allowed. Further, by rotating the rotor 4 to another rotational position, the flow of the sample through both the tubes 8 and 9 can be restricted. Further, since the sample passes through the inside of the tube and the sample does not flow through the inside of the valve body as in the switching valve of patent document 2, dust generated from the switching valve 3 does not contaminate the sample. The rollers 6a and 6b of the switching valve 3 of the present embodiment are cylindrical with straight side surfaces. However, the present invention is not limited to this, and may be configured in a barrel shape that tapers from the center portion of the cylindrical shape toward both ends as another embodiment. The rollers 6a and 6b press, i.e., squeeze, the tubes 8 and 9 in cooperation with the pressing members 17a and 17b to close the flow inside the tubes 8 and 9. Therefore, if an excessive force is repeatedly applied to the folded portions of the pipes 8 and 9 to be pressed, plastic deformation occurs in the folded portions, and the pipes are prematurely degraded. Therefore, by making the roller of the portion in contact with the folded portion have a barrel shape so as to have a smaller diameter than the central portion, the pressing force acting on the folded portion can be reduced, and early deterioration of the tubes 8 and 9 can be prevented.

Next, the syringe pump 18 provided in the inhalation/ejection device 2 of the present invention will be described. Fig. 6(a) is a front view of the suction/discharge device 2 according to the present embodiment, and fig. 6(b) is a side view. In fig. 6, portions of the syringe pump 18 are shown in cross section for ease of understanding the description. The suction/discharge device 2 of the present embodiment is configured such that a syringe-type syringe pump 18 is driven by a motor 19. The substrate 11 of the suction/discharge device 2 includes brackets 21 and 22 for positioning and fixing the cylinder portion 20 at a predetermined position. Further, the base plate 11 is provided with a piston holder 24 that engages with the piston portion 23 and moves the piston portion 23 forward and backward with respect to the cylinder portion 20. The piston bracket 24 is fixed to a moving member of a feed screw mechanism 25 that is coupled to a rotary shaft of the motor 19 and converts a rotational motion of the motor 19 into a linear motion. The piston holder 24 moves forward and backward in conjunction with the rotation of the motor 19, and thereby the piston portion 23 moves forward and backward with respect to the cylinder portion 20. Further, the motor 19 is a stepping motor capable of accurately controlling the rotation direction and the rotation angle. In the following configuration, the operation of the motor 19 is controlled by the pump control unit 26, and the motor 19 is operated in a predetermined rotational direction or rotational position by a signal from the pump control unit 26.

The motor 19 and the pump control unit 26 constitute a pump driving unit that moves the piston 23 of the syringe pump 18 forward and backward to a predetermined position with respect to the cylinder unit 20. With this configuration, the sample can be sucked and discharged with high accuracy. The rotor driving unit and the pump driving unit operate in cooperation with each other, and the sample stored in the tank 28 can be accurately sucked by a predetermined amount and discharged from the discharge nozzle 27.

To operate the suction/discharge device 2, first, a suction/discharge unit including the suction-side tube 8, the discharge-side tube 9, and the syringe pump 18 is attached to a predetermined position of the suction/discharge device 2. The tubes 8 and 9 are positioned and fixed in parallel with each other at predetermined positions between the rotor 4 and the pressing members 17a and 17b by the tube fixing member 15 attached to the switching valve 3. The pipe fixing member 15 is formed with a groove having a width smaller than the diameter of the pipes 8 and 9 in a plate-like member. The pipes 8, 9 are fixed by pressing the pipes 8, 9 into the grooves. Further, since the pipes 8 and 9 to be press-fitted are fixed only by the reaction force of the pipes themselves, the pipes 8 and 9 can be easily detached from the pipe fixing member 15 and replaced. The pipe fixing members 15 are respectively attached above and below the rotor 4 of the switching valve 3. When the tubes 8 and 9 are replaced, it is preferable to stop the rotor 4 of the switching valve 3 at a position where the rollers 6a and 6b do not press the tubes 8 and 9. The position where the tubes 8 and 9 are not pressed by the rollers 6a and 6b is referred to as a tube open position (see fig. 7 (a)). The motor 19 is stopped at a position where the piston portion 23 of the attached syringe pump 18 is maximally pushed into the cylinder portion 20, that is, at a position where the internal volume of the cylinder portion 20 is minimized. Further, the ends of the pipes 8 and 9 disposed near the rotor 4 are connected to the two input/output sides of the Y-pipe connector Y, respectively. The Y-pipe connector Y has two input/output portions on one side and one input/output portion on the other side, and one input/output side of the other side is connected to the tip of the syringe pump 18.

First, the tubes 8 and 9 are attached to the syringe pump 18. Next, the rotor 4 is rotated to a position where the rollers 6a and 6b close the flow inside the tubes 8 and 9 between the pressing members 17a and 17 b. The position where the respective tubes 8 and 9 are closed to flow inside by the corresponding rollers 6a and 6b (see fig. 7 b) is referred to as a tube closed position. In a state where the inside of each of the tubes 8 and 9 is closed, the other end of the sample suction side tube 8 is connected to a sample tank 28 in which a sample is stored, and the other end of the discharge side tube 9 is connected to a discharge nozzle 27. This completes the preparation of the inhalation/ejection device 2 of the present invention. The ejection nozzle 27 is a front end member for ejecting the sample supplied from the syringe pump 18 to a predetermined container, and will be described in detail later.

Next, the operation of sucking and discharging the sample by the suction and discharge device 2 of the present embodiment will be described. First, the motor 12 is operated to rotate the rotor 4, which is located at the rotational position where the flow inside the pipes 8 and 9 is closed, to the first position where the flow inside the suction-side pipe 8 is open and the flow inside the discharge-side pipe 9 is closed (see fig. 8 a). Subsequently, the motor 19 is operated to retract the piston portion 23 of the syringe pump 18 relative to the cylinder portion 20. By the retraction operation of the piston portion 23, the sample stored in the tank 28 is sucked into the suction/discharge unit. At this time, since the pipe 9 is in a closed state, air in the external environment is not sucked through the discharge nozzle 27. When the piston portion 23 is retracted to a predetermined position, the motor 19 is stopped.

Next, the motor 12 is operated to rotate the rotor 4 to a second position where the flow inside the suction side tube 8 is closed and the flow inside the discharge side tube 9 is opened (see fig. 8 (b)). Thereafter, the motor 19 is operated to advance the piston portion 23 relative to the cylinder portion 20, whereby the sample and air sucked into the cylinder portion 23 are discharged to the outside through the pipe 9 and the discharge nozzle 27. When the discharge operation is completed, the motor 12 is driven in the opposite direction to the previous one, and the rotor 4 is rotated to a position where the rollers 6a and 6b close the inside flow of the corresponding tubes 8 and 9. This completes a series of suction and discharge operations performed by the suction and discharge device 2. In addition, in the case where the air inside the tubes 8 and 9 is not completely discharged in the series of suction and discharge operations, the interior of the suction and discharge unit can be filled with the sample by repeating the above-described suction and discharge operations, and a correct amount of the sample can be discharged from the discharge nozzle 27 by the subsequent suction and discharge operations.

The switching valve 3 of the present embodiment controls the flow of the sample or gas in the tube by rotating the rotor 4 in a predetermined direction and angle to selectively close or open the suction-side tube 8 and the discharge-side tube 9. Namely, the following features are provided: by rotating the rotor 4, the rollers 6a and 6b are operated in cooperation with the corresponding pressing members 17a and 17b to press the tubes 8 and 9 from the outside, thereby closing the spaces inside the tubes 8 and 9 and closing the internal flow. Here, the closing operation of the discharge side tube 9 will be described with reference to fig. 9. The rotor 4 depicted by a two-dot chain line in fig. 9(a) is a position where the internal flow of the suction-side tube 8 is closed and the internal flow of the discharge-side tube 9 is opened. This position is referred to as the second position. From this position, the motor 12 is operated to rotate the rotor 4 counterclockwise by an angle α on the paper surface. By this rotation operation, the discharge side tube 9 is also sandwiched between the roller 6b and the pressing member 17b from the open state to a state in which the internal flow is closed (the state of the rotor 4 shown by the solid line in fig. 9 a). In addition, while the rotor 4 is rotated by a predetermined angle in this way, the roller 6a and the pressing member 17a maintain the inside of the suction-side tube 8 in a closed state.

Next, as shown by the solid line in fig. 9(b), the motor 12 is operated to rotate the rotor 4 by an angle β in the counterclockwise direction. By this operation, the roller 6a is disengaged from the area through which the inside of the closed tube 8 flows in cooperation with the pressing member 17a, and the tube 8 is opened to flow through the inside. During the rotational movement of the rotor 4 at the angle β, the roller 6b maintains the state in which the discharge-side tube 9 is pressed against the pressing member 17 b. That is, the roller 6b moves while revolving around the center axis C2 of the shaft 16b in the pressing region. During the operation of the roller 6b, the discharge side tube 9 is pressed in the direction opposite to the discharge direction by the roller 6b and the pressing member 17 b. Further, since the roller 6b moves while rotating (rotating) with respect to the tube 9, the tube 9 is not damaged greatly by friction. By pressing the tube 9 in the direction opposite to the flow direction of the sample, dripping from the discharge nozzle 27 after the discharge of the sample is completed can be prevented. This is the same function as the known suckback valve. In this way, the switching valve 3 of the present invention can close and suck back the sample inside the tube by the rotation operation of the rotor 4.

The sample (culture medium) is produced by adjusting nutrients and antibiotics necessary for cell growth, and chemicals for cell detachment used when collecting cells. The sample supplied to the dispensing device or the medium exchange device is stored in a low-temperature environment to prevent deterioration or the like. Since cells are usually cultured at 37 ℃ in an environment, if a sample stored at a low temperature is supplied at the time of medium replacement, the cells are greatly damaged by the low temperature of the sample temperature. In order to prevent damage due to low temperature, the sample is supplied while being heated to a predetermined temperature by a heater. The heater is provided in the suction side tube 8, the discharge side tube 9, and the discharge nozzle 27. In this way, if the discharge side tube 9 or the discharge nozzle 27 is provided with a heater, even if the discharge of the sample is stopped, the sample remaining in the tube is heated by the heater, and the volume thereof increases, and the remaining liquid droplets are scattered from the tip of the discharge nozzle 27. The suck-back effect of the switching valve 3 of the present invention is useful for preventing such a problem that the remaining liquid droplets fall.

Next, a suction/discharge unit including the tubes 8 and 9 and the syringe pump 18, which is applied to the suction/discharge device 2 of the present invention, will be described. The tubes 8 and 9 applied to the suction/discharge device 2 of the present invention are preferably made of a material having a high flexibility and having a restoring force, such as silicone rubber, polyolefin, fluororubber, or a thermoplastic elastomer, if it is considered that the tubes are pressed from the outside by the rollers 6a and 6b of the switching valve 3. In addition, a general glass or resin pump may be used as the syringe pump 18. However, in view of ease of handling and disposal cost, it is preferable to use a resin such as polypropylene or polyethylene. In particular, the suction/discharge device 2 of the present invention has a structure that facilitates replacement of the tubes 8 and 9 or the syringe pump 18. Therefore, by a simple replacement operation, all of the tubes 8 and 9 or the syringe pump 18 that have been used can be discarded after the suction and discharge of the sample, and a new tube or syringe pump can be used in the next suction and discharge operation. This can easily prevent contamination of the sample or specimen. Further, if a known connection member such as a screw connector or a one-touch connector corresponding to the connection member provided in the connected tank 29 or nozzle 27 is provided in advance at the tip of the pipes 8 and 9, the replacement of the components can be performed in a shorter time. In particular, it is desirable to prepare a unit in which the tubes 8 and 9, the syringe pump 18, and the connecting member are integrated as a set, and the unit is sealed by performing a known sterilization process such as autoclave sterilization or gamma ray sterilization.

Next, a second embodiment of the present invention will be described with reference to fig. 10.

In the switching valve 3 provided in the first embodiment, the rotation center axis C of the rotor 4 main body is arranged at a position shifted from the straight line L1 (position shifted from the straight line L1) connecting the center axes C1, C2 of the shafts 16a, 16b of the rollers 6a, 6b arranged at both ends of the rotor 4. In contrast, in the switching valve 3 'according to the second embodiment of the present invention, the central axis C of the shaft 10 of the rotor 4' is arranged on the straight line L1 connecting the central axes C1, C2 of the shafts 16a, 16 b. In this way, in the first and second embodiments, the positional relationship between the rotational center axis C of the rotor and the straight line connecting the rotational axis C1 of the rollers 6a and 6b and C2 is different. Therefore, in the second embodiment, in order to perform various opening and closing operations of the position where both the tubes 8 and 9 are completely closed, the position where both the tubes are completely released, and the first position and the second position, it is also necessary to replace the positions of the pressing members in accordance with the positions of the respective rotation shafts.

Fig. 10 is a schematic front view of a switching valve 3' according to a second embodiment of the present invention. In the rotor 4' of the present embodiment, as in the first embodiment, substantially cylindrical rollers 6a and 6b are rotatably fixed to the rotor body via shafts 16a and 16b at both ends of the rotor body. The rotor 4' is rotatable by a motor 12 around a central axis C of the shaft 10. By the rotation operation of the rotor 4', the rollers 6a and 6b revolve on a circular orbit a1 around the central axis C of the shaft 10. The pressing members 17c and 17d are arranged laterally symmetrically outside the revolution orbit a1 of the rollers 6a and 6 b. The surfaces of the pressing members 17c and 17d facing the rotor 4' are formed along an arc a2 having a radius larger than the revolution orbit a1 of the rollers 6a and 6 b. According to the above configuration, the rotor 4' is rotated in a predetermined direction by the operation of the motor 12, and the rollers 6a and 6b are also revolved. Thereby, the rollers 6a and 6b approach or separate from the corresponding pressing members 17c and 17 d. By this approach or separation, the tube 8 disposed between the roller 6a and the corresponding pressing member 17c and the tube 9 disposed between the roller 6b and the corresponding pressing member 17d are pinched closed or opened, whereby the internal flow of the tubes 8 and 9 can be controlled.

In the first embodiment, the rotation center axis C of the rotor 4 is arranged at a position offset from the straight line connecting the rotation center axes C1, C2 of the rollers 16a, 16b, and the pressing areas of the pressing pipes 8, 9 are formed in a shape symmetrical to the straight line L3 extending in the horizontal direction through the rotation center axis C. In contrast, in the second embodiment, the rotation center axis C of the rotor 4 is arranged on a straight line connecting the rotation center axes of the rollers 16a and 16 b. Therefore, the pressing areas of the pressing tubes 8, 9 are not at positions symmetrical with respect to the straight line L3 extending in the horizontal direction through the rotation center axis C. The pressing members 17C and 17d are disposed so that both the tubes 8 and 9 can be closed or released simultaneously or only one of the tubes can be closed when the pressing regions corresponding to the rollers 16a and 6b are rotated by a predetermined angle around the central axis C as a rotation center.

Further, although the tubes 8 and 9 in the first embodiment are arranged in parallel to each other and arranged in the vertical direction, the tubes 8 and 9 in the present embodiment are arranged in bilateral symmetry with respect to a straight line extending in the vertical direction at a predetermined angle to each other. Thus, when the rotor 4' is located at the first position where only the discharge-side tube 9 is closed or the second position where only the suction-side tube is closed, the open state of the open-side tube can be secured. Tubes 8 and 9, which are disposed at an angle to each other, are connected to the tube connector Y. The other end of the tube connector Y is connected to the syringe pump 18 below the switching valve 3'.

The rotor 4 'of the switching valve 3' of the present embodiment is configured to be rotatable about the central axis C as the rotation center by the motor 12 and the motor control unit 14, as in embodiment 1. Further, the rotation movement to the rotation position stored in advance in the motor control unit 14 can be performed. With the above configuration, the sample stored in the tank 28 can be sucked and discharged from the discharge nozzle 27 in cooperation with the pump driving unit that drives the syringe pump 18.

Next, a medium exchange device 30 using the aspiration/ejection device 2 of the present invention will be described. FIG. 11 is a perspective view showing the outline of the medium exchange device 30 of the present invention. The medium replacement device 30 of the present embodiment is a device for replacing a solution called a medium containing water or nutrients in microorganisms or cells cultured in the container 29 at predetermined intervals. The medium replacement operation is performed by first removing the old medium in the container 29 by suction and then adding a new medium. In the medium exchange device 30 of the present embodiment, the old medium is removed through the suction nozzle 31, and the new medium is supplied through the discharge nozzle 27 connected to the suction/discharge device 2 of the present invention.

The discharge nozzle 27 of the medium exchange device 30 of the present invention is fixed to a beam member 32 provided across the upper part of the main body of the medium exchange device 30. One end of the discharge side tube 9 is connected to the base end portion of the nozzle 27. The other end of the discharge side tube 9 is connected to a syringe pump 18 of the suction/discharge device 2.

The portion of the discharge nozzle 27 below the portion fixed to the beam member 32 is formed in an elongated cylindrical shape, and the tip portion thereof has a shape curved at a predetermined angle. By discharging the culture medium in a state where the curved tip portion is brought close to the inner wall of the container 29, the culture medium is accumulated on the bottom surface of the container 29 along the inner wall of the container 29. This makes it possible to supply the culture medium to the container 29 without generating air bubbles. Further, the cells adhered to the bottom surface of the container 29 are not peeled off from the bottom surface by the potential energy of the supplied culture medium.

In order to supply the culture medium to the container 29 through the discharge nozzle 27, first, the container 29 is moved by the stage transfer unit 44 to a predetermined position where the tip of the discharge nozzle 27 is located below the upper end of the side wall of the container 29 (see fig. 12 (a)). Then, the stage transfer unit 44 is operated to horizontally move the container 29 to a position where the side wall of the container 29 abuts on the tip end portion of the discharge nozzle 27. After the movement is completed, the medium is ejected from the ejection nozzle 27 (see fig. 12 (b)). The ejected culture medium spreads on the side wall of the container 29 and is gradually supplied from the bottom surface of the container 29.

The discharge nozzle 27 is provided with a heater for raising the temperature of the culture medium stored at a low temperature to a temperature at which microorganisms or cells to be cultured are not damaged. The heater provided in the present embodiment is a cartridge heater in which a heating element is incorporated. The heater is detachably inserted into a temperature raising block 27a having a flow path for the medium formed therein. The temperature of the heater is controlled by a temperature control means, not shown, and can be supplied at a temperature that is optimum for the temperature culture of the ejected culture medium. The discharge nozzle 27 is detachably fixed by screw fastening or the like so as to be easily attachable to and detachable from the beam member 32.

The suction nozzle 31 provided in the medium exchange device 30 of the present embodiment is fixed to the beam member 32, and the proximal end portion thereof is connected to the distal end portion of a medium discharge tube 34 connected to a known suction pump P. The tip of the suction nozzle 31 is shaped into a disposable pipette tip 33 that can be attached and detached. The pipette tip 33 is a tip made of elastic resin and is inserted into the tip of the nozzle 31. The pipette tip 33 is fixed by fastening from the outside using elastic force. Further, the culture medium sucked by the suction nozzle 31 may deteriorate with time after a certain time has elapsed after the supply, and may be contaminated by dust and bacteria floating in the air. If the culture medium of another container 29 is aspirated by the pipette tip 33 that aspirates the contaminated culture medium, so-called cross contamination that spreads the contaminating substance on the other container 29 also occurs due to the pipette tip 33. In order to prevent such cross contamination between the vessels 29, the suction nozzle 31 provided in the medium replacement device 30 of the present embodiment is configured to replace the pipette tip 33 every time the old medium is sucked.

The discharge nozzle 27 may be configured such that the pipette tip 33 can be replaced. When the tip of the discharge nozzle is linear as in the case of the suction nozzle 31, the same components as the suction tip holder 37 and the tip remover 39 described above may be used as the discharge nozzle. In the case where the tip of the discharge nozzle 27 is curved as in the present embodiment, it is necessary to provide a special pipette tip holder and tip remover that conform to the shape of the tip.

The container 29 for replacing the culture medium is positioned and placed at a predetermined position by a positioning member 36a on a container table 36 disposed on a replacement table 35. In addition to the container 29, the tip holder 37 is placed at a predetermined position on the exchange table 35 by a positioning member 38. The tip rack 37 accommodates the plurality of pipette tips 33 in a vertically upright posture so as to be attachable to the nozzles 27, 31. Further, a tip remover 39 for removing the pipette tips 33 attached to the discharge nozzles 27 and the suction nozzles 31, and a tip cartridge 40 for storing the removed pipette tips 33 are attached to the exchange table 35. The exchange table 35 is movable in the X-axis direction, the Y-axis direction, and the Z-axis direction by a table transfer portion 44.

The exchange table 35 is disposed on a moving table 46 provided in the Y-axis drive mechanism 44 a. The Y-axis drive mechanism 44a includes a motor 41, a feed screw mechanism 42 connected to the motor 41, and a pair of slide rails 43 that guide in the Y-axis direction. The moving table 46 and the exchange table 35 disposed on the moving table 46 are moved in the Y-axis direction by the operation of the motor 41. The Y-axis drive mechanism 44a is disposed on the X-axis table 50. The X-axis table 50 is moved in the X-axis direction by an X-axis drive mechanism 44b including a motor 45, a feed screw mechanism 46 connected to the motor 45, and a pair of slide rails 47 that guide in the X-axis direction. The X-axis drive mechanism 44b is disposed on the base 51. Further, the exchange table 35 is movable in the Z direction, i.e., the vertical direction, with respect to the moving table 46 by a Z-axis drive mechanism 44c including a motor 49 and a feed screw mechanism and a guide mechanism, not shown.

The motors 41, 45, and 49 included in the medium exchange device 30 of the present embodiment can be operated to predetermined positions instructed in advance with high accuracy by using stepping motors capable of controlling the angles of the rotating shafts. The operations of the motors 41, 45, and 49 and the suction/discharge device 2 are controlled by signals transmitted from a medium replacement control unit (not shown, the same applies hereinafter). With the above configuration, the container 29 placed on the exchange table 35, all the pipette tips 33 and the tip remover 39 stored in the tip rack 37, and the like can be moved relative to the suction nozzle 31 and the discharge nozzle 27 in the X direction, the Y direction, and the Z direction. By moving in these respective directions, the pipette tip 33 can be attached to the suction nozzle 31, detached (attached/detached) from the suction nozzle 31, and moved relative to the container 29. Further, by setting the delivery position of the container 29 in advance, the container 29 or the tip rack 37 conveyed by a known automatic conveying apparatus can be delivered.

In addition to the above-described configuration, as shown in fig. 13, in order to improve the efficiency of removing the old medium, the medium exchange device 30 of the present embodiment includes a tilting mechanism 52 for tilting the container table 36 on which the container 29 is placed. The tilting mechanism 52 is a mechanism that is configured by a known drive source and mechanism such as a motor and an air cylinder and tilts the container table 36 on which the container 29 is placed by a predetermined angle. By inclining the container table 36, the remaining part of the culture medium sucked through the suction nozzle 31 can be collected at one place.

The method of sucking the medium using the tilting mechanism 52 is as follows. First, when a large amount of waste culture medium remains in the container 29, the container table 36 is maintained in a horizontal state as shown in fig. 13 (a). Then, when the amount of the discarded culture medium is small and remains, the tilting mechanism 52 is operated to tilt the container table 36 by a predetermined angle. Further, the container table 36 is tilted, and the table transfer portion 44 is operated to move the container table 36 so that the tip of the pipette tip 33 attached to the suction nozzle 31 comes into contact with the lowest position of the container 29 (see fig. 13 (b)). This enables the old medium to be removed from the container 29 without leaving a residue.

Next, the procedure of the medium replacement operation performed by the medium replacement device 30 of the present embodiment will be described. First, the medium replacement controller operates the motors 41, 45, and 49 of the medium replacement device 30 and the table transfer unit 44 to move the replacement table 35 to a predetermined position in the receivable container 29. When the container 29 requiring the replacement of the culture medium is placed on the container table 36, the culture medium replacing apparatus 30 drives the motors 41, 45, and 49 to move the container 29 to a position where the suction nozzle 31 can suck the culture medium. When the container 29 is moved to a position where the tip of the suction nozzle 31 intrudes into the culture medium, the old culture medium in the container 29 is sucked by the suction force of the known pump P through the pipette tip 33 and the suction nozzle 31, and the culture medium replacement controller removes the old culture medium to be discarded by suction while inclining the container 29 by the above-described procedure.

When the removal of the old medium is completed, the medium replacement control unit operates the tilting mechanism 52 to return the container 29 from the tilted posture to the horizontal posture. Thereafter, the motors 41, 45, and 49 are operated to move the container 29 to a position where the discharge nozzle 27 can discharge the culture medium into the container 29. When the movement of the container 29 is completed, the suction/discharge device 2 operates to supply a predetermined amount of the culture medium stored in the tank 28 to the container 29. Then, when the supply of the culture medium is completed, the culture medium replacement control unit moves the replacement table 35 to the transfer position with respect to the container 29 of the conveyance device. Thus, a series of medium replacement actions are completed.

Next, the replacement operation of the pipette tip 33 attached to the suction nozzle 31 will be described. The pipette tips 33 are stored in a plurality of tip racks 37 in an upright posture attachable to the tip portion of the suction nozzle 31. In general, the tip rack 37 accommodates a predetermined number of pipette tips 33 in a predetermined array so as to correspond to the arrangement of the culture sections (wells) of a microplate having 96 wells, 384 wells, or 1536 wells, which is a well-known culture container. For ease of explanation, the medium replacement device 30 according to the present embodiment is configured to correspond to 96 wells. As shown in FIG. 11, the tip rack 33 mounted on the medium changer 30 of the present embodiment is configured such that 8 rows of rows each containing 12 pipette tips 33 at a predetermined interval in the X-axis direction are arranged at a predetermined interval in the Y-axis direction. When the tip rack 37 is set at a predetermined position on the exchange table 35 manually or by a known conveyance device, the medium exchange controller operates the table transfer unit 44 to move the exchange table 35 so that the target pipette tip 33 is positioned directly below the suction nozzle 31. Then, the medium replacement control unit operates the Z-axis drive mechanism 44c to raise the replacement table 35 and the tip holder 37 to a predetermined height. The medium replacement control unit stops the operation of the motor 49 at a position where the pipette tip 33 is attached to the tip attachment portion of the suction nozzle 31. Thereafter, the motor 49 is operated in the reverse direction, and the exchange table 35 is lowered to a position before the raising operation. Thereby, the pipette tips 33 stored in the tip rack 37 are attached to the suction nozzle 31.

Next, an operation of detaching the attached pipette tip 33 from the suction nozzle 31 will be described. In order to detach the pipette tips 33 from the suction nozzle 31, a tip remover 39 equipped on the exchange table 35 is used. The tip remover 39 provided in the medium exchange device 30 of the present embodiment has a discharge hole in the shape of a circular hole larger than the diameter of the pipette tip 33 and a long hole larger than the diameter of the tip attachment portion of the suction nozzle 31 and smaller than the diameter of the pipette tip 33, which are connected to each other, in the upper surface cover portion of a hollow cylindrical member.

After the culture medium is completely sucked, the culture medium replacement control section operates the stage transfer section 44 to move the large circular hole portion of the tip remover 39 to a position directly below the discharge nozzle 27. Subsequently, the medium replacement control section operates the Z-axis drive mechanism 44c to raise the tip remover 39 and insert the target pipette tip 33 into the tip remover 39. Next, the tip remover 39 is moved in the horizontal direction, and the tip mounting portion of the suction nozzle 31 is moved to the long hole portion of the plate member. The medium replacement control unit operates the Z-axis drive mechanism 44c to lower the tip remover 39, thereby engaging the pipette tip 33 with the elongated hole portion and detaching the pipette tip 33 from the suction nozzle 31. The detached pipette tips 33 are housed in a tip magazine 40 disposed below the tip remover 39. When the removal of the pipette tip 33 is completed, the medium replacement control unit operates the stage transfer unit 44 to move the tip holder 37 toward the suction nozzle 31 in order to attach a new pipette tip 33 to the tip of the suction nozzle 31. Thus, the medium exchange device 30 of the present embodiment can automatically perform suction and discharge of a sample and exchange of the disposable pipette tip 33. As described above, the discharge nozzle 29 may have a shape to which the pipette tip 33 can be attached.

The material of the discharge nozzle 27 provided in the medium exchange device 30 of the present embodiment is preferably metallic with high thermal conductivity, and in particular, stainless steel that can withstand sterilization by an autoclave or sterilization by hydrogen peroxide gas can be used repeatedly after sterilization. Further, the suction nozzle 31 is fastened by a screw so as to be easily attachable to and detachable from the beam member 32. Further, since the attachment and detachment of the pipette tip 33 are repeated, the material of the suction nozzle 31 is preferably made of a metal harder than the pipette tip 33. In particular, stainless steel that can withstand sterilization by an autoclave or sterilization by hydrogen peroxide gas can be used repeatedly even after sterilization. In addition, when the sterilization process of the suction nozzle 31 is performed, it is desirable that the tube 34 for discharging the culture medium connected to the suction nozzle 31 is sterilized together with the suction nozzle 31, or is discarded and replaced with a new tube 34. Furthermore, if the aspiration/ejection device 2 and the aspiration/ejection module 48 according to the present invention are used instead of a known pump for aspirating an old culture medium, even if contamination occurs, the contaminated module can be discarded and a new module can be attached to easily remove the contaminated portion.

In the above description, the medium replacement device 30 is described as an embodiment of a device using the aspiration/ejection device 2 of the present invention. However, the present invention can be applied to a dispensing apparatus 53 used for various tests such as biochemical reaction tests of substances in the fields of drug development and screening, biotechnology, and the like, in addition to the medium exchange apparatus 30. Fig. 14 is a perspective view showing a dispensing device 53 including another embodiment of the suction/discharge device 2 of the present invention.

The dispensing device 53 of the present embodiment includes a tip holder 37 for storing a plurality of disposable pipette tips 33, a sample container 54, a dispensing table 56, a dispensing nozzle 57, a nozzle transfer unit 58, a tip remover 39, and a tip cassette 40 disposed below the tip remover 39 and for storing the pipette tips 33 removed by the tip remover 39 and waste liquid. The sample container 54 stores a sample for testing. The dispensing table 56 mounts a reaction vessel 55 having a plurality of reaction wells at a predetermined position by a positioning member. The dispensing nozzle 57 sucks a sample from the sample container 54 and discharges the sample to a predetermined reaction well of the reaction container 55. The nozzle transfer unit 58 moves the dispensing nozzle 57 in the X direction, the Y direction, and the Z direction. The tip remover 39 removes the pipette tip 33 that has finished dispensing the sample.

The suction/discharge device 2 provided in the dispensing device 53 is connected to a dispensing nozzle 57 via a tube 9, and sucks the sample in the sample container 54 and discharges the sample to each well of the reaction container 55 by the reciprocating operation of the syringe pump 18. The nozzle transfer unit 58 includes a Y-axis drive mechanism 59 for horizontally transferring the dispensing nozzle 57 in the Y-axis direction, an X-axis drive mechanism 60 supported by the Y-axis drive mechanism 59 for horizontally transferring the dispensing nozzle 57 in the X-axis direction, and a Z-axis drive mechanism 61 supported by the X-axis drive mechanism 60 for vertically moving the dispensing nozzle 57 in the Z-axis direction (vertical direction). Each of the drive mechanisms 58, 59, and 60 includes a drive source, not shown, by which the dispensing nozzle 57 is movable in the X direction, the Y direction, and the Z direction. Further, each driving source, not shown, provided in the dispensing device 53 according to the present embodiment can be moved to a predetermined position specified in advance with high accuracy by using a stepping motor capable of controlling the angle of the rotation shaft. The operations of the drive source and the suction/discharge device 2 are controlled by an operation signal transmitted from a dispensing control unit (not shown, the same applies hereinafter).

The proximal end of the suction-side pipe 8 of the suction/discharge device 2 of the present embodiment is connected to a pressure transmission water tank 62 for storing pressure transmission water. The pressure transmission water is a liquid that is sucked and discharged by the suction and discharge device 2 provided in the present embodiment, and is a liquid for transmitting a pressure generated by the operation of the syringe pump 18 at the time of the dispensing operation to the dispensing nozzle 57. Functional water such as ion exchange water, electrolytic water, pure water, etc. is mainly used. When a new suction/discharge unit 48 is provided, the syringe pump 18 provided in the suction/discharge device 2 is operated as a preparation operation before sample dispensing, and pressure-transmitting water is filled into the tubes 8 and 9, the dispensing nozzle 57, and the pipette tip 33.

As an operation of filling the pressure-transmitting water, first, the dispensing control unit rotates the rotor 4 to a position where the suction side tube 8 is opened and the discharge side tube 9 is closed. Thereafter, the piston portion 23 of the syringe pump 18 is retreated, and the pressure transmission water is sucked from the pressure transmission water tank 62. Subsequently, the rotor 4 is rotated to a position where the discharge side tube 9 is opened and the suction side tube 8 is closed. Thereafter, the piston portion 23 of the syringe pump 18 is advanced to discharge the air filled in the tubes 8 and 9 and the syringe pump 18. Thereafter, the above operation is repeated, whereby the piping system of the suction/discharge device 2 is filled with the pressure transmission water.

Next, a dispensing operation performed by the dispensing device 53 of the present embodiment will be described. Before starting the dispensing operation, the dispensing control unit moves the piston unit 23 of the syringe pump 18 of the suction/discharge device 2 backward, and sucks a predetermined amount of air from the tip of the pipette tip 33 filled with pressure transmission water (see fig. 15 (a)). This is a measure for preventing mixing of the pressure transmission water and the sample, and the amount of air suction is controlled by the amount of operation of the motor 19 that operates the piston portion 23 of the syringe pump 18. In addition, when performing this operation, first, the dispensing control unit operates the motor 12 to rotate and move the rotor 4 of the suction/discharge device 2 to a position where the suction side tube 8 is closed and the discharge side tube 9 is opened. Next, the dispensing control unit operates the nozzle transfer unit 58 to transfer the dispensing nozzle 57 to which the pipette tip 33 having sucked air is attached to the sample container 54 directly above. Thereafter, the tip of the pipette tip 33 is lowered to a position where it enters the sample stored in the sample container 54. Thereafter, the motor 19 of the syringe pump 18 is operated to retract the piston 23, thereby sucking a predetermined amount of the sample. When the suction of the sample is completed, the dispensing device 53 operates the nozzle transfer unit 58 to move the pipette tip 33 up to the upper side of the sample container 54. Subsequently, the dispensing control unit moves the piston 23 of the syringe pump 18 of the suction/discharge device 2 backward again, and further sucks a predetermined amount of air from the tip of the pipette tip 33. Then, the tip of the pipette tip 33 is lowered to submerge into the sample stored in the sample container 54. Thereafter, the motor 19 is operated again to retract the piston 23, thereby sucking a predetermined amount of the sample. The dispensing control unit repeats this operation a predetermined number of times. Thereby, as shown in fig. 15(b), a plurality of regions of a predetermined amount of sample separated by a layer of a predetermined amount of air are formed in the pipette tip 33.

Subsequently, the dispensing control unit moves the pipette tip 33 to a position above the predetermined reaction container 55, and lowers the tip of the pipette tip 33 into the predetermined reaction well formed in the reaction container 55. When the lowering operation is completed, the dispensing device 53 operates the motor 19 of the syringe pump 18 to supply a sample of one region amount to the reaction well. When the supply to one reaction well is completed, the dispensing control unit operates the nozzle transfer unit 58 and the suction/discharge device 2, and repeats the operation of supplying the sample in the pipette tip 33 to the next reaction well.

In the dispensing device 53, the pipette tip 33 attached to the dispensing nozzle 57 may be replaced. For example, in operations such as seeding or pipetting of cell suspensions of different types, trypsin treatment or concentration of Phosphate Buffered Saline (PBS) in connection with a subculture operation, or cell washing using the PBS, the pipette tip 33 is replaced in order to prevent mixing with other specimens. The replacement operation of the pipette tips 33 is the same as described above, and the new pipette tips 33 are mounted on the tip rack 37 by detaching the pipette tips 33 by the tip remover 39.

When the attachment of the new pipette tip 33 is completed, the dispensing control unit operates the nozzle transfer unit 58, moves the dispensing nozzle 57 to which the pipette tip 33 is attached above the tip remover 39, operates the syringe pump 18 of the suction/discharge device 2, fills the newly attached pipette tip 33 with pressure transmission water, and then sucks a predetermined amount of air to prevent the pressure transmission water from being mixed with the sample. Next, the nozzle transfer unit 58 is operated to aspirate the sample, and the dispensing nozzle 57 and the pipette tip 33 are moved toward the sample container 54. In this way, the dispensing device 53 of the present embodiment can automatically perform an accurate dispensing operation of a large amount of samples by continuously performing replacement of the disposable pipette tip 33 and suction and discharge of the samples.

Further, the dispensing device 53 of the present embodiment includes one dispensing nozzle 57, but may include a plurality of dispensing nozzles 57. In this case, it is desirable to arrange the dispensing nozzles 57 in accordance with the number of wells arranged in a lattice pattern in the reaction vessel 55 to be dispensed and the separation distance between the wells so that the suction of the sample and the supply of the sample by the plurality of dispensing nozzles 57 can be performed simultaneously and efficiently. Further, it is preferable to arrange the tip remover 39 and the tip holder 37 according to the positions of the plurality of dispensing nozzles 57 so that the pipette tips 33 of the plurality of dispensing nozzles 57 can be efficiently replaced at the same time. Further, if one suction/discharge device 2 is provided for one dispensing nozzle 57, the dispensing amount for each dispensing nozzle 57 can be accurately controlled. With the above configuration, the time for the dispensing operation can be shortened without deteriorating the accuracy of the dispensing amount.

Next, an automatic culture system 65 in which a culture medium exchange device 30 having the configuration shown in FIG. 11 and including the suction/discharge device 2 of the present invention and a culture device 63 including a conveyance mechanism 64 of a container 29 are combined will be described. FIG. 16 is a sectional view showing an automatic culture system 65 according to the present embodiment. The culture apparatus 63 is also generally called an incubator, and includes a constant temperature chamber 66 for storing a container 29 for storing a plurality of samples to be cultured or examined, and a known means for maintaining environmental conditions such as temperature, humidity, and carbon dioxide concentration. The culture apparatus 63 included in the automatic culture system 65 of the present embodiment includes, in addition to a device for environment maintenance, not shown, a container rack 67 on which the container 29 is placed on each of a plurality of shelf sections, a stand 68 on which a plurality of the container racks 67 are radially placed, and a stand driving unit 69 that rotates and moves the stand 68 in a horizontal plane. As a drive source of the stage drive unit 69, a stepping motor capable of accurately controlling the rotation angle of the rotation shaft is used. Furthermore, the culture apparatus 63 included in the automatic culture system 65 of the present embodiment includes a plurality of shielding plates 70 that shield an opening for carrying in and out the container 29. The culture apparatus 63 of the present embodiment further includes a magnetic coupling mechanism for transmitting the rotational driving force of the stage driving unit 69 disposed outside the thermostatic chamber 66 to the mount 68 disposed inside the thermostatic chamber 66 by magnetic force. Further, by disposing the automatic culture system 65 of the present embodiment in a clean room maintained in a sterile environment, contamination can be prevented to a higher degree. In particular, since the culture can be automatically performed without passing through a human body which is the largest contamination source, the arrangement in the clean room is particularly effective.

The transport mechanism 64 included in the automatic culture system 65 of the present embodiment includes a finger 71 that supports the container 29 from below, and a finger driving unit 72 that supports the finger 71 and transfers the finger to a predetermined position in the front-rear direction. The finger driving portion 72 includes a forward/backward driving portion 72a for supporting the finger 71 and moving the finger 71 forward and backward in the left-right direction of the figure, i.e., forward and backward directions, along a guide not shown, a rotary driving portion 72b for supporting and rotating the forward/backward driving portion 72a, and a vertical driving portion 72c for supporting and vertically moving the rotary driving portion 72b along the guide 73. The elevation driving unit 72c can elevate and lower the rotation driving unit 72b to a position where the finger 71 can access the container 29 placed on the container table 36 of the medium replacement device 30 placed above the culture device 63. Further, each of the finger portion driving portions 72 uses a stepping motor as a driving source, which can perform accurate angle control of the rotation axis. With this configuration, the finger drive unit 72 and the stage drive unit 69 can transfer the finger 71 and the container 29 supported by the finger 71 to a predetermined shelf section stored in the control device in advance in the automatic culture system 65 by an operation command transmitted from the control device not shown.

The elevation driving unit 72c includes an engagement mechanism 74 that engages with an engagement hole formed in the shielding plate 70 to open and close the shielding plate 70. The engaging mechanism 74 includes an engaging pin fixed above the finger 71 of the elevation driving portion 72c and engaging with an engaging hole formed in the shielding plate 70. The engagement mechanism 74 has a mechanism for moving the engagement pin forward and backward, and a stepping motor capable of adjusting the amount of the engagement pin to be fed out is provided as a drive source of the mechanism for performing the forward and backward movement. To open the shield plate 70, first, the up-down driving portion 72c is moved up and down to a predetermined position, and then the engagement mechanism 74 advances the engagement pin toward the engagement hole of the shield plate 70. When the engagement pin is inserted into the engagement hole and the engagement mechanism 74 and the shield plate 70 are engaged with each other, the elevating drive portion 72c moves upward, and the engaged shield plate 70 and the shield plate 70 arranged above the shield plate 70 are lifted, whereby the finger portion 71 can access the opening of the container holder 67. When the access of the finger part 71 to the container rack 67 is completed, the elevation driving part 72c descends to close the opening, and then the engaging mechanism 74 retracts the engaging pin to the original position. The access of the finger portion 71 to the container rack 67 means an operation of placing the container 29 held by the finger portion 71 on a predetermined shelf section of the container rack 67, or an operation of lifting the container rack 67 placed on the predetermined shelf section of the container rack 67 from below by the finger portion 71 and carrying out the container rack to the outside of the thermostatic chamber 66.

Next, the operation of the automatic culture system 65 according to the present embodiment will be described. In order to replace the culture medium in the container 29 stored in the thermostatic chamber 66 of the culture apparatus 63, first, the stage driving unit 69 rotates the stage 68 to a position where the target container 29 faces the shielding plate 70 so that the conveyance mechanism 64 can access the target container 29. Subsequently, the elevation driving portion 72c and the engagement mechanism 74 operate in cooperation, and the corresponding shielding plate 70 is opened. Thereafter, the transport mechanism 64 operates the finger drive section 72 to support the container 29 on the fingers 71 and transport the container out of the thermostatic chamber 66, and thereafter, the transport mechanism descends to close the shielding plate 70. Thereafter, the conveyance mechanism 64 operates the elevation drive unit 72c to raise the finger 71 to a position where the container 29 supported by the finger 71 can be placed on the container table 36 provided in the medium changer 30. At this time, the medium exchange device 30 moves the stage transfer unit 44 to move the container stage 36 disposed on the exchange stage 35 to a position where the finger can access (see fig. 11). When the container table 36 moves to a position where the fingers 71 can be accessed, the conveyance mechanism 64 operates the finger driving section 72 to place the container 29 supported by the fingers 71 on the container table 36. When the placement of the container 29 is completed, the conveyance mechanism 64 stands by until the medium replacement operation of the medium replacement device 30 is completed. The medium replacement operation performed by the medium replacement device 30 thereafter is the same as the operation already described, and therefore is omitted here.

When the medium exchange is completed, the medium exchange device 30 again operates the stage transfer unit 44 to move the exchange stage 35 to a position where the finger can access the container 29 placed on the container stage 36. When the container table 36 moves to a position where the fingers 71 can access, the conveyance mechanism 64 operates the finger driving section 72, picks up the container 29 placed on the container table 36, supports the container on the fingers 71, and lowers the container to a position corresponding to a predetermined shelf section of a predetermined container rack 67. Thereafter, the shielding plate 70 is opened in the same manner as in the previous operation, and the container 29 is placed on a predetermined shelf section of a predetermined container rack 67 disposed in the thermostatic chamber 66. When the placement is completed, the conveyance mechanism is lowered, and the raised shielding plate 70 is lowered to close the opening, thereby completing the conveyance operation. When the culture period of the sample is completed, the automatic culture system 65 operates the culture apparatus 63 and the conveyance mechanism 64, carries the target container 29 out of the thermostatic chamber 66, conveys the container 29 to a predetermined transfer position, and transfers the container to the next step.

As described above, by using the automatic culture system 65 of the present embodiment, the culture medium replacement operation can be automated without using a human hand for cells or the like being cultured, and therefore, the burden on the operator can be reduced. In addition, since it does not go through the human hand, contamination can be prevented. Further, since the quantitative culture medium replacement is mechanically performed with certainty, the culture conditions of the respective samples caused by the culture medium replacement operation do not differ, and stable culture can be performed. The technical scope of the present invention is not limited to the above-described embodiments, and various modifications can be added without departing from the spirit of the present invention.

Description of the symbols

2 suction and discharge device

3. 3' switching valve

4. 4' rotor

6a, 6b roller

8 suction side pipe

9 ejection side pipe

15 pipe fixing part

17a, 17b, 17c, 17d pressing member

18 injection pump

30 medium exchange device

53 dispensing device

63 culture device

65 automatic culture system.