Dispensing apparatus

A dispensing apparatus includes: a dish mounting portion having a mounting surface mounted with a dish having a bottom surface and a side surface surrounding the bottom surface; a syringe, arranged above the dish mounting portion, having a nozzle configured to discharge liquid toward an interior of the dish; and a first driving portion configured to change the syringe in direction with respect to a first axis as a center, wherein the first axis is orthogonal to a normal to the mounting surface of the dish mounting portion.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims the benefit of priority to Japanese Patent Application No. 2011-155925, filed Jul. 14, 2011, of which full contents are incorporated herein by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to a dispensing apparatus.

2. Description of the Related Art

A dispensing apparatus configured to discharge liquid from a nozzle using a syringe, etc., has been used for various purposes.

For example, Japanese Patent Application Laid-open Publication No. 2009-291103 discloses an automatic cell culture apparatus including a dispensing apparatus (pipette device) to be used in a pipetting operation applied to a dish (or culture container).

Here, for example, when a cell is cultivated in a dish or a cell is passaged, operations are performed such as an operation of replacing a medium in a dish with a new medium, an operation of recovering a medium from a dish after cell cultivation is finished, an operation of recovering cell, an operation of isolating cells and an operation of adjusting a colony to a predetermined size. When these operations are performed, such considerations are required that an old culture media, reagent, and cell suspension are efficiently recovered as well as a new medium and reagent are promptly spread over an entire cell culture surface.

However, for instance, as illustrated inFIG. 11, in related dispensing apparatuses, peripheral portions in an inner bottom surface of a dish include areas on which liquid discharged from a nozzle of a syringe is unable to be poured directly. Therefore, there is such a problem that cells remains in areas on which discharged liquid cannot be poured directly. There is also another problem that cells such as a lightly attached cell, which is nearly detached by detachment solution such as trypsin, and a cell, which is deposited on and adhered to a bottom surface of a dish, cannot be recovered without directly pouring liquid to the cells for a predetermined period of time with a predetermined flow rate.

When liquid is discharged from a nozzle by tilting a dish as illustrated inFIG. 11A, since the nozzle of a syringe is directed in a vertical direction and the nozzle therefore interferes with a side surface of the tilted dish, liquid discharged from the nozzle cannot be directly poured to an area in the vicinity of the uppermost part (area illustrated as R1) out of an area of circumference of an inner bottom surface of a dish. Further, since liquid discharged from the nozzle is promptly accumulated in an area in the vicinity of the lowermost part (area illustrated as R2) out of an area of circumference of an inner bottom surface of a dish, it is also impossible to directly pour liquid discharged from a nozzle onto the area.

Furthermore, when liquid is discharged from a nozzle by tilting a dish as illustrated inFIG. 11B, since the nozzle of a syringe is directed in a vertical direction and the nozzle therefore interferes with a side surface of the dish, as in the case of the area R1, it is impossible to directly pour liquid discharged from a nozzle to areas in the vicinity of the areas intermediate between the uppermost part and the lowermost part (areas illustrated as R3and R4) out of an area of circumference of an inner bottom surface of the dish.

SUMMARY OF THE INVENTION

In order to achieve the above described object, a dispensing apparatus according to an aspect of the present invention, includes: a dish mounting portion having a mounting surface mounted with a dish having a bottom surface and a side surface surrounding the bottom surface; a syringe, arranged above the dish mounting portion, having a nozzle configured to discharge liquid toward an interior of the dish; and a first driving portion configured to change the syringe in direction with respect to a first axis as a center, wherein the first axis is orthogonal to a normal to the mounting surface of the dish mounting portion.

Other features of the present invention will become apparent from descriptions of this specification and of the accompanying drawings.

DETAILED DESCRIPTION OF THE INVENTION

At least the following details will become apparent from descriptions of this specification and of the accompanying drawings.

A configuration of a dispensing apparatus100according to an embodiment of the present invention will be described with reference toFIG. 1.

FIG. 1depicts a configuration of cell culture equipment as an example of the application of a dispensing apparatus100including a dispensing mechanism101according to an embodiment of the present invention. The dispensing apparatus (or cell culture equipment)100as illustrated inFIG. 1is configured including: a syringe1for dispensing liquid; and a dish mounting portion22which is arranged relatively lower than the syringe1and is capable of mounting a dish5configured to contain liquid to be dispensed, and further including a driving portion8configured to move the syringe1and the dish mounting portion22. The driving portion8is configured including a syringe driving portion3configured to move the syringe1and a dish driving portion4configured to move the dish mounting portion22.

The syringe1includes a nozzle11configured to discharge liquid.

The dish5is a cell culture dish which is formed including a circular bottom surface and a side surface surrounding the circumference of the bottom surface, for example, and is made of resin, for example.

Liquid includes a culture medium for cultivating cells in the dish5, for example, as well as trypsin and PBS (Phosphate Buffered Saline), for example, depending on purposes.

The dish mounting portion22has a flat dish mounting surface23in a circular shape to be matched with the circular dish5, and includes positioning means24by which the center of an inner bottom surface of the dish5and the center of the dish mounting surface23coincide with each other when the dish5is mounted and prevented from easily deviating from each other.

The syringe driving portion3is capable of controlling the position and the posture of the syringe1. This enables control of a discharging direction of liquid which is to be discharged from the nozzle11of the syringe1.

The dish driving portion4is capable of controlling the position, posture and further rotation of the dish mounting portion22.

Then, by control of the syringe driving portion3and the dish driving portion4, the relative position between the nozzle11of the syringe1and the dish5is controlled, thereby being able to relatively move the nozzle11of the syringe1to a position at which liquid is dispensed toward the dish5.

A configuration of the dispensing mechanism101included in the dispensing apparatus100according to an embodiment of the present invention will be described with reference toFIG. 2.

The dispensing mechanism101as illustrated inFIG. 2is configured including the syringe1, a control unit2, a filter12, pumps P1and P2and valves V1and V2. The control unit2is configured to output control signals Sp1and Sp2as well as Sv1and Sv2for controlling the pumps and the valves, respectively.

The pump P1is a pump for discharging configured to introduce the external air into the syringe1and generate a pressure to discharge liquid retained in the syringe1via the nozzle11. The pump P2is a pump for sucking configured to discharge the gas (air) retained in the syringe1and generate a pressure (negative pressure) to sucking liquid into the syringe1via the nozzle11.

The valve V1is connected so as to open/close a passage between the syringe1and the pump P1(i.e., first passage). The valve V2is connected so as to open/close a passage between the syringe1and the pump P2(i.e., second passage). As each of the valves, a solenoid valve (i.e., electromagnetic valve), a motor-operated pinch valve, etc., for example, that are controllable by a control signal can be used.

The first and the second passages are merged and diverged at one point and the filter12such as membrane filter is inserted to a passage between the merging/diverging point and the syringe1in order to prevent liquid retained in the syringe1from being contaminated by getting mixed with unwanted bacteria. Passages between the external air and the pumps P1and P2may also be merged/diverged as appropriate.

===Configuration of Driving Portion===

Subsequently, a configuration of the driving portion8will be described with reference toFIG. 3toFIG. 5.

FIG. 3is a side view of the dispensing apparatus100.FIG. 4is a front view of the dispensing apparatus100.FIG. 5is a top surface view of the dispensing apparatus100.

The syringe driving portion3includes a first driving mechanism31, a second driving mechanism32and a third driving mechanism33. The dish driving portion4includes a fourth driving mechanism34and a fifth driving mechanism35.

The first driving mechanism31includes a first servo motor51in the interior thereof, and as illustrated inFIG. 3, is capable of changing a direction of the nozzle11of the syringe1with respect to a first rotation axis parallel to a Y axis as the center. The first rotation axis is also orthogonal to a normal (perpendicular line) with respect to the dish mounting surface23. The direction of the nozzle11of the syringe1is changed to the direction of a depression angle (first direction) by driving the first servo motor51. For simplicity of description, the directions in which the nozzle11of the syringe1is changed by the first servo motor51are also referred to as up and down directions.

The second driving mechanism32includes a second servo motor52in the interior thereof, and as illustrated inFIG. 4, is capable of changing the direction of the nozzle11of the syringe1in a plane, which is determined by the direction of the Y axis and the direction of the nozzle11of the syringe1, with respect to a second rotation axis perpendicular to the plane as the center. In an embodiment of the present invention, the second rotation axis is orthogonal to the normal with respect to the dish mounting surface23and perpendicular to the first rotation axis, and thus directions of the nozzle11to be changed by the second driving mechanism32are directions (i.e., second direction) orthogonal to the above described depression angle direction (first direction). For simplicity of description, the directions orthogonal to the depression angle direction are also referred to as left and right directions.

The third driving mechanism33includes a third servo motor53in an interior thereof, and as illustrated inFIG. 3, is capable of sliding and moving the entire syringe11in the direction of the Z axis (vertical direction). The third driving mechanism33is configured including a crank structure as illustrated inFIG. 3, wherein an end portion of a first rod36, configured to be rotationally moved by the third servo motor53with respect to a third rotation axis parallel to the Y axis as the center, is connected one end of a second rod37, and the other end of the second rod is connected to the first driving mechanism31, the second driving mechanism32and the syringe1. This enables the movement of the syringe1in directions toward and away from the dish mounting portion22.

The fourth driving mechanism34includes a fourth servo motor54in the internal thereof, and as illustrated inFIG. 3, is capable of changing the inner bottom surface of the dish5, which is mounted on the dish mounting portion22, from a horizontal state to a state where it is tilted toward the syringe1by rotationally moving the dish mounting portion22with respect to a fourth rotation axis (dish first axis) parallel to the Y axis as the center.

The fifth driving mechanism35includes a fifth servo motor55in the interior thereof, and as illustrated inFIG. 5, is capable of rotating the dish mounting portion22with respect to a fifth rotation axis (dish second axis) vertical to the dish mounting surface23of the dish mounting portion22as the center. In an embodiment of the present invention, since the fifth rotation axis runs through the center of the dish mounting surface23, the dish mounting portion22is rotated with respect to the fifth rotation axis as the center, thereby being able to rotate the dish5mounted on the dish mounting portion22using the center of the bottom surface of the dish5as an axis of rotation. The fifth driving mechanism35is capable of driving to rotate it in a range of ±180 degrees, for example, using the fifth rotation axis as the center as illustrated inFIG. 5.

The fifth rotation axis of the fifth driving mechanism35is arranged so that the fifth rotation axis and the second rotation axis of the second driving mechanism32intersect in the same plane. Then, all of the first rotation axis of the first driving mechanism31, the third rotation axis of the third driving mechanism33and the fourth rotation axis of the fourth driving mechanism34are arranged so as to be orthogonal to this plane.

Therefore, the dish mounting portion22is tilted toward the syringe1by the fourth driving mechanism34as well as the direction of the nozzle11of the syringe1is moved in the up and down directions by the first driving mechanism31, thereby being able to direct the nozzle11of the syringe1so as to be perpendicular to the center of the bottom surface of the dish5mounted on the dish mounting portion22.

It is also possible to change the direction of the nozzle11of the syringe1in the depression angle direction (up and down directions, first direction), that is, the first direction in which two opposing points in areas, in which the inner bottom surface of the dish5is in contact with the inner side surface thereof, are connected, by further driving the first driving mechanism31based on the direction, in which a normal extends from the nozzle11of the syringe1to the center of the bottom surface of the dish5when the nozzle11of the syringe1is directed perpendicularly to the center of the bottom surface.

It is also possible to change the direction of the nozzle11of the syringe1in a direction intersecting with the depression angle direction (left and right directions, second direction) by further driving the second driving mechanism32based on the direction in which the normal extends from the nozzle11of the syringe1to the center of the bottom surface of the dish5when the nozzle11is directed perpendicularly to the center of the bottom surface.

Then, it is possible to direct the nozzle11of the syringe1over the entire surface on the inner bottom surface of the dish5by combination of the first driving mechanism31and the second driving mechanism32.

For instance, the nozzle11of the syringe1can be directed to the predetermined position in a ring-shaped area in which the inner bottom surface of the dish5is in contact with the inner side surface thereof (e.g., position in the vicinity of the uppermost part of the inner bottom surface of the tilted dish5in the ring-shaped area), and the nozzle11of the syringe1can be further changed in direction so as to be directed along the ring-shaped area.

It is also possible to direct the nozzle11of the syringe1not only to the ring-shaped area but also to arbitrary positions on the inner bottom surface of the dish5, and thus the direction of the nozzle11of the syringe1can be changed along the predetermined route on the inner bottom surface of the dish5, for example.

It should be noted that each of the first to fifth driving mechanisms31to35includes a rotary potentiometer, for example, which is capable of detecting a rotational angle of each of the first to fifth rotation axes and position detecting means configured with an origin sensor and a rotary encoder, etc. This enables accurate position control of the syringe1and the dish mounting portion22performed by the first to fifth driving mechanisms31to35.

Furthermore, an end position of the nozzle at the time of dispensing is set at a position at which the nozzle is not in contact with the bottom surface of the dish5as well as dispensed liquid does not splash toward the outside of the dish5considering the dispensing flow rate and the moving speed of a nozzle tip.

===Configuration of Control Unit===

As illustrated inFIG. 6, the dispensing apparatus100according to an embodiment of the present invention includes the control unit2, a storage unit41, the servo motors51to55, the pumps P1and P2, the valves V1and V2. The control unit2is connected to a touch panel42and a display43.

The touch panel42and the display43may be realized as constituents of the dispensing apparatus100or may also be realized by using an external control device such as personal computer connected to the control unit2in a communicable manner.

The control unit2is a device configured to control operations of the entire dispensing apparatus100. The control unit2includes a microcomputer capable of executing programs stored in the storage unit41, for example.

The storage unit41is configured to store programs to be executed by the control unit2as well as control data and tables to be referred to when the control unit2executes the programs.

The touch panel42is a device configured to be used by an operator of the dispensing apparatus100in order to input various kinds of instructions to the dispensing apparatus100such as operation start and operation stop. The operator also inputs, from the touch panel42, target positions of the syringe1and the dish mounting portion22, positional information of each of the rotation axes of the first to fifth driving mechanisms31to35, or the like, at the initial setting and/or resetting of the dispensing apparatus100, etc., for example, thereby being able to perform an accurate dispensing operation according to the length of the syringe1and the size of the dish5, etc.

The display43is a device configured to output a control state of the dispensing apparatus100and various kinds of warnings and the like to the operator of the dispensing apparatus100.

The control unit2is configured to control the servo motors51to55, the pumps P1and P2and the valves V1and V2by executing programs stored in the storage unit41based on the instruction inputted from the touch panel42.

===Operational Example of Dispensing Apparatus===

Subsequently, an operation of the dispensing apparatus100according to an embodiment of the present invention will be described with reference toFIG. 7toFIG. 10, by giving an example of a series of operations to recover adherent cells, which have been detached by a detachment solution such as trypsin, and floating cells using a medium.

FIG. 7depicts an outline of an operation to recover cells from the dish5using the dispensing apparatus100according to an embodiment of the present invention.FIG. 8exemplifies a flow of controlling the dispensing apparatus100when cells are recovered from the dish5.

InFIG. 7, firstly, the dispensing apparatus100sucks liquid, such as medium solution, stored in a reservoir6which is provided at a predetermined location in the vicinity of the dispensing apparatus100, into the syringe1(filling operation). The dispensing apparatus100then discharges liquid retained in the syringe1to the dish5(i.e. dispensing operation). The dispensing apparatus100then sucks liquid containing cells in the dish5into the syringe1(i.e. sucking operation) and the liquid retained in the syringe1is discharged to a storage tank7which is placed at a predetermined location in the vicinity of the dispensing apparatus100, (i.e. discharging operation). That is, cells are recovered.

Since the filling operation and the sucking operation are the same operation in terms of taking in liquid into the syringe1, the pumps P1and P2and the valves V1and V2operate in the same manner. However, the filling operation is an operation to take in liquid from the reservoir6into the syringe1, whereas the sucking operation is different in that liquid is taken in from the dish5into the syringe1, and therefore these operations are described separately for convenience of explanation.

Of course, in addition to the above operations, the dispensing apparatus100is also able to suck liquid from the dish5so as to discharge the liquid in the reservoir6, suck liquid from the dish5so as to discharge the liquid in the dish5, and suck liquid from the reservoir6so as to discharge the liquid in the reservoir6. It is also possible to suck liquid from the reservoir6so as to discharge the liquid in the storage tank7.

In the following description, in any case, positions to which the syringe1should be moved in order to perform the filling operation, the dispensing operation, the sucking operation and the discharging operation are referred to as a filling position, a dispensing position, a sucking position and a discharging position, respectively.

Next, an example of an operation of recovering a cell which is performed by the dispensing apparatus100according to an embodiment of the present invention will be described specifically using a flowchart inFIG. 8. It should be noted that, if the cell to be recovered is an adherent cell, the cell is supposed to have been detached in advance by a detachment solution such as trypsin, and thereafter a medium with serum is poured into the dish5to stop a detachment action and the cell results in a state of floating in the medium, being nearly detached and lightly attached, or being deposited on and adhered to the bottom surface of the dish5. Whereas, if the cell to be recovered is a floating cell, the cell is supposed to be floating in a medium or be deposited on and adhered to the bottom surface of the dish5.

When the dispensing apparatus100starts operating (S11), first, the control unit2drives the driving portion8to cause the dish mounting portion22to be tilted toward the syringe1at a predetermined angle (S12). Specifically, the control unit2drives the fourth servo motor54to cause the dish mounting portion22to rotate on the fourth rotation axis (dish first axis). A target rotation amount and a target rotational position are stored in the storage unit41in advance. The control unit2causes the dish mounting portion22to tilt up to a target angle comparing a detection signal from a rotary potentiometer with a target rotation amount and a target rotational position stored in the storage unit41.

Next, the control unit2drives the driving portion8to direct the nozzle11of the syringe1to an sucking position which is a second area (S13), and thereafter performs an operation of sucking liquid retained in the second area containing cells that have been washed off (S14).

The control unit2drives the first to third servo motors51to53in order to direct the syringe1to the second area and causes component elements of the first to third driving mechanisms31to33to rotate at predetermined angles on the first to third rotation axes, respectively. Target rotation amounts or target rotational positions for directing the syringe1to the second area are stored in the storage unit41in advance. The control unit2directs the syringe1to the second area while comparing a detection signal from a rotary potentiometer with target rotation amounts and target rotational positions stored in the storage unit41.

The present dispensing apparatus100is capable of changing the direction of the nozzle11to the first direction and the second direction based on the direction of a normal which extends from the nozzle11of the syringe1to the bottom surface of the dish5when the nozzle11is directed perpendicularly to the bottom surface, thereby being able to direct the nozzle11to the second area. Then, as illustrated inFIG. 10A, the nozzle11of the syringe1can be directed to the second area at predetermined angles with respect to the inner bottom surface and the inner side surface of the dish5without interference of the nozzle11of the syringe1with the bottom surface and the side surface of the dish5.

As such, the present dispensing apparatus100can suck liquid retained in the second area of the tilted dish5.

Further, the present dispensing apparatus100causes the syringe1to move in a perpendicularly downward direction by driving the third driving mechanism33when the nozzle11is directed to the second area. It is therefore possible to arrange the tip of the nozzle11in a deepest spot in liquid retained in the second area of the tilted dish5, thereby being able to recover liquid which has flown down to the second area without leaving the liquid behind therein.

In the sucking operation, under control by the control unit2, the pump P1is stopped while the pump P2is driven to open the valve2in a state where the valve V1is closed, and using pressure (negative pressure) generated in the pump P2, liquid retained in the second area of the dish5is sucked from the nozzle11of the syringe1(pump driven suction).

Next, in the dispensing apparatus100, the control unit2drives the driving portion8to direct the nozzle11to a dispensing position (S15) based on the direction of a normal extending from the nozzle11of the syringe1to the bottom surface of the dish5when the nozzle11is directed perpendicularly to the bottom surface, thereby performing a dispensing operation (S16).

The dispensing position is a predetermined position within a ring-shaped area in which the inner bottom surface of the tilted dish5is in contact with the inner side surface thereof, for example.

The dispensing position will be described with reference toFIG. 9andFIG. 10.FIG. 9is a diagram exemplifying dispensing positions when the dish5mounted on the tilted dish mounting portion22is viewed from a negative side to a positive side in the X axis direction and viewed from a negative side to a positive side in the Y axis direction.

FIG. 10Ais a diagram when the dish5mounted on the tilted dish mounting portion22is viewed from a negative side to a positive side in the Y axis direction, and illustrating respective directions of the nozzle11when dispensing positions of the nozzle are in the first area and the second area.FIG. 10Bis a diagram when the dish5mounted on the tilted dish mounting portion22is viewed from a direction parallel to the bottom surface of the dish5, and illustrating respective directions of the nozzle11when dispensing positions of the nozzle are in the first area and the second area.

A dispensing position when performing the dispensing operation in a present embodiment is the first area illustrated inFIG. 9in the vicinity of the uppermost part in a ring-shaped area in which the inner bottom surface of the tilted dish5is in contact with the inner side surface thereof.

The control unit2drives the first to third servo motors51to53to cause component elements of the first to third driving mechanisms31to33to rotate at predetermined angles on the first to third rotation axes, respectively, in order to direct the syringe1to the first area. Target rotation amounts and target rotational positions are stored in the storage unit41in advance. The control unit2directs the syringe1to the first area comparing a detection signal from a rotary potentiometer with target rotations and target rotational positions stored in the storage unit41.

In the present dispensing apparatus100, the nozzle1can be directed to the first area by changing the direction of the nozzle11in the first direction and the second direction based on the direction of a normal extending from the nozzle11of the syringe1to the bottom surface of the dish5when the nozzle11is directed perpendicularly to the bottom surface of the dish5, thereby, as illustrated inFIG. 10A, being able to direct the nozzle11of the syringe1to the first area at predetermined angles with respect to the inner bottom surface and the inner side surface of the dish5, without interference of the nozzle11with the bottom surface and the side surface of the dish5.

Return toFIG. 8, in the dispensing operation (S16), under control by the control unit2, the pump P2is stopped while the pump P1is driven to open the valve V1in a state where the valve V2is closed, using pressure generated in the pump P1, liquid retained in the syringe1is discharged (pump driven discharge).

With respect to the amount of liquid to be discharged from the syringe1in the dispensing operation, the relationship between the time to drive the pumps and the amount to be discharged is defined in advance. The storage unit41stores data indicative of this relationship, and the control unit2controls the valves V1and V2and the pumps P1and P2so that a predetermined amount of liquid is discharged from the syringe1.

As such, it becomes possible in the present dispensing apparatus100to directly pour liquid discharged with pressure from the nozzle11of the syringe1toward the above first area of the dish5. Liquid which has been discharged directly toward the first area flows down while spreading over the inner bottom surface of the dish5. It is therefore possible to effectively wash away cells that are lightly attached or adhered to the inner bottom surface of the dish5.

Furthermore, in the dispensing apparatus100according to an embodiment of the present invention, when the dispensing operation is executed, the control unit2drives the driving portion8to cause the dish mounting portion22to rotate on a rotation axis passing through the center of the bottom surface of the dish5and perpendicular to the bottom surface.

As a result, liquid can be thus discharged while rotating the dish5, thereby being able to directly pour liquid, discharged with pressure from the nozzle11of the syringe1to the first area, over the circumference of the inner bottom surface of the dish5. Thus, it becomes possible to effectively wash off cells that are lightly attached or adhered to the inner bottom surface of the dish5.

When a predetermined amount of liquid is discharged from the syringe1, the control unit2performs control such that the above described rotation of the dish mounting portion22is stopped and discharging of liquid from the syringe1is stopped.

The dispensing apparatus100performs a dispensing finishing operation (S17). In the dispensing finishing operation, in order to prevent the nozzle11of the syringe1from dripping droplets and bubbles, for example, the control unit2drives the driving portion8to bring the tip of the nozzle11into contact with the inner side surface of the dish5, for example, thereby removing droplets and babbles at the tip of the nozzle11.

When the dispensing finishing operation is ended, a predetermined amount of liquid discharged from the syringe1is retained in the second area of the dish5as illustrated inFIG. 9. The second area is an area in the vicinity of the lowermost part out of an area in which the inner bottom surface of the dish5mounted on the tilted dish mounting portion22is in contact with the inner side surface thereof.

Next, the control unit2drives the driving portion8while discharging of liquid from the syringe1is stopped, and directs the nozzle11of the syringe1to the second area (S18), and thereafter an operation is performed of sucking liquid retained in the second area containing cells that have been washed off (S19).

In order to direct the syringe1to the second area, the control unit2drives the first to third servo motors51to53to rotate the component elements of the first to third driving mechanisms31to33to rotate at predetermined angles on the first to third rotation axes, respectively. Target rotation amounts and target rotational positions for directing the syringe1to the second area are stored in the storage unit41in advance. The control unit2directs the syringe1to the second area comparing a detection signal from a rotary potentiometer with target rotation amounts and target rotational positions stored in the storage unit41.

In the present dispensing apparatus100, the nozzle11of the syringe1can be directed to the second area, by changing the direction of the nozzle11to the first direction and the second direction based on the direction of a normal extending from the nozzle11to the bottom surface of the dish5when the nozzle11is directed perpendicularly to the bottom surface, thereby, as illustrated inFIG. 10A, being able to direct the nozzle11of the syringe1to the second area at predetermined angles with respect to the inner bottom surface and the inner side surface of the dish5, respectively, without interference of the nozzle11with the bottom surface and the side surface of the dish5.

As such, in the present dispensing apparatus100, liquid retained in the second area of the tilted dish5can be sucked.

Further, in the present dispensing apparatus100, the syringe1is moved in a perpendicularly downward direction by driving the third driving mechanism33when the nozzle11is directed to the second area. Thus, the tip of the nozzle11can be arranged in the deepest spot in liquid retained in the second area of the tilted dish5, thereby being able to recover liquid which has flown down to the second area without leaving the liquid behind therein.

In the sucking operation, under control by the control unit2, the pump P1is stopped while the pump2is driven to open the valve V2in a state where the valve V1is closed, and using pressure (negative pressure) generated in the pump P2, liquid retained in the second area of the dish5is sucked from the nozzle11of the syringe1(pump driven suction).

The dispensing apparatus100executes the above described process from S15to S19the predetermined number of times, i.e., three to five times in a present embodiment (S20). If the predetermined number of times is set at twice or more, the dispensing apparatus100executes the above described process from S15to S19until the number of times the process from S15to S19is executed reaches the predetermined number of times. By executing the process from S15to S19several times, it becomes possible to recover more cells more reliably, when recovering cells lightly attached or adhered to the inner bottom surface of the dish5.

In the dispensing apparatus100, when the process from S15to S19is executed the predetermined number of times (S20; Yes), the control unit2drives the driving portion8to move the syringe1to an discharging position (S21) in order to perform a discharging operation in which liquid sucked the last time is dispensed in the storage tank7(S22). That is, sucked cells are recovered in the tank.

The discharging position is a position at which liquid is discharged from the nozzle11provided in a predetermined location.

The control unit2drives the first to third servo motors51to53to rotate the components elements of the first to third driving mechanism31to33at predetermined angles on the first to third rotation axes, respectively, in order to move the syringe1to the discharging position. Target rotation amounts and target rotational positions for moving the syringe1to the discharging position are stored in the storage unit41in advance. The control unit2causes the syringe1to move to the discharging position comparing a detection signal from a rotary potentiometer to target rotation amounts and target rotational positions stored in the storage unit41.

In the discharging operation, similarly to the dispensing operation, under control by the control unit2, a pump driven discharge is performed, and using pressure generated in the pump P1, liquid, which has been sucked from the second area of the dish5into the syringe1and contains cells, is discharged into the storage tank7(pump driven discharge).

In the discharging operation, it is desirable to take some measures to prevent the surrounding from being contaminated by the pump driven discharge, such as emitting liquid while deeply inserting the nozzle11into the storage tank7having enough depth, and bringing the tip of the nozzle11into contact with the inner wall of the storage tank7.

The control unit2then determines if the discharging operations of S21and S22, i.e., the recovering process, are executed the predetermined number of times or twice to three times in a present embodiment (S23), and when it reaches the predetermined number of times, a series of the sequences is ended (S26).

On the other hand, when it does not reach the predetermined number of times (S23; No), the control unit2drives the driving portion8to move the syringe1to a filling position (position at which the nozzle11of the syringe1is in liquid stored in the reservoir6inFIG. 7) (S24) and a filling operation is performed (S25).

In the filling operation, under control by the control unit2, the pump P1is stopped while the pump P2is driven to open the valve V2in a state where the valve V1is closed, and using pressure (negative pressure) generated in the pump P2, new liquid (e.g., medium) is sucked into the syringe1(pump driven suction). When a predetermined amount has been sucked, the pump P2is stopped to close the valve V2.

Then, returning to the step S15, the control unit2executes the process from S15to S19the predetermined number of times again. In this case, pouring (dispensing) and sucking are repeated using, e.g., a medium, which is fresh and newly filled from the reservoir6. As such, in addition to pouring and sucking using the original medium, pouring and sucking using the new medium are further executed, thereby being able to recover cells more reliably. In an embodiment of the present invention, the process is repeated the number of times obtained by (the predetermined number of times of S20)×(the predetermined number of times of S23).

As described above, according to the dispensing apparatus100in an embodiment of the present invention, it becomes possible to directly pour liquid discharged from the nozzle11of the syringe1to any areas including peripheral portions in the inner bottom surface of the dish5.

Therefore, for example, in the process of recovering cells from the dish5, more cells that are lightly attached or adhered to the bottom of the dish5can be washed away, thereby being able to improve cell recovery efficiency. Further, a sufficient amount of liquid to wash off cells can be directly poured, for a predetermined period of time with a predetermined flow rate, onto such cells that are difficult to be recovered only by flow of liquid flowing down and dispensation of liquid for a short period of time, such as cells that are nearly detached by detachment solution such as trypsin and cells that are deposited on and adhered to the bottom surface of the dish, thereby improving the recovery rate.

As an example, a case of a general-sized dish is considered which is usually called a 100-mm dish. An inner bottom portion of the 100-mm dish is about 90 [mm] in diameter.

When areas on which discharged liquid could not be directly poured by the conventional devices are estimated to be a ring-shaped area of about 5 [mm] in the circumference of the inner bottom portion, an area on which discharged liquid could directly poured by the conventional devices was considered to be only an area of 40 [mm]×40 [mm]×3.14=5024.0 [mm2].

In the present dispensing apparatus100, discharged liquid can be poured directly over the entire inner bottom surface, and therefore discharged liquid can be directly poured on an area of 45 [mm]×45 [mm]×3.14=6358.5 [mm2].

When comparing between the above areas, 6358.5 [mm2]/5024.0 [mm2]=1.27 is obtained, and thus efficiency improvement of about 27 [%] can be realized.

In the dispensing apparatus100according to an embodiment of the present invention, as illustrated inFIG. 9andFIG. 10, when liquid is discharged from the nozzle11of the syringe1, the nozzle11of the syringe1is directed to an area (first area) in the vicinity of the uppermost part in a ring-shaped area in which the inner bottom surface of the tilted dish5is in contact with the inner side surface thereof. Thus, liquid, which has been directly discharged from the nozzle11of the syringe1to the above first area, flows down, while spreading over the inner bottom surface of the dish5, thereby being able to efficiently recover cells that are lightly attached or adhered to the inner bottom surface of the dish5.

Further, it is also possible to rotate the dish mounting portion22on a rotation axis passing through the center of the bottom surface of the dish5and perpendicular to the bottom surface when liquid is discharged from the nozzle11of the syringe1. That is, the dish mounting portion22is rotated along a plane parallel to the bottom surface of the dish5. This enables discharging of liquid while rotating the dish5, thereby being able to directly pour liquid, which has been discharged from the nozzle11of the syringe1to the above first area, over the circumference of the inner bottom surface of the dish5. Further, in this case, due to a synergistic effect of the flow of liquid discharged from the nozzle11and the rotational speed of the dish5, the flow velocity of liquid is increased on the inner bottom surface of the dish5, thereby being able to more efficiently recover cells that are lightly attached or adhered to the dish5.

When the dish mounting portion22is rotated, the dish mounting portion22may make one or more rotations in the same direction, for example. This enables directly pouring liquid throughout the entire circumference of the above ring-shaped area of the dish5.

Alternatively, when the dish mounting portion22is rotated, the dish mounting portion22may be rotated in the same direction and a reverse direction in an alternate manner. For example, the dish mounting portion22may be rotated in the reverse direction every other rotation or may be rotated in the reverse direction every other half rotation. This also enables directly pouring of liquid throughout the entire circumference of the above ring-shaped area of the dish5. Moreover, particularly, by changing the direction of rotation, liquid discharged from the nozzle11can be poured down from a different direction depending on a rotational direction when the liquid is poured down on the dish5, thereby being able to further improve an effect of recovering cells that are lightly attached or adhered to the dish.

Further, when liquid is discharged from the nozzle11of the syringe1, the direction of the nozzle11may be moved from the area in the vicinity of the uppermost part (first area) to the area in the vicinity of the lowermost part (second area) in the ring-shaped area in which the inner bottom surface of the tilted dish5is in contact with the inner side surface thereof. This causes liquid which has been discharged from the nozzle11of the syringe1directly to the above first area to flow down while spreading over the inner bottom surface of the dish5, as well as the nozzle11is moved toward the second area, thereby being able to directly pour liquid to an area on the moving route. Furthermore, in this case, the direction of the nozzle11may be combined with a direction in which two areas (third area and fourth area) are connected that oppose to each other in the parallel direction in the ring-shaped area where the inner bottom surface of the tilted dish5is in contact with the inner side surface thereof.

Further, when liquid is discharged from the nozzle11of the syringe1, the direction of the nozzle11may be moved to up and down directions while being changed alternately to left and right directions (second direction) so as to scan the entire inner bottom surface of the dish5. This can cause liquid discharged from the nozzle11of the syringe1to flow down while spreading over the inner bottom surface of the dish5, as well as cause liquid to be directly poured to a wide area on the route to move the nozzle11. In this case, the direction of the nozzle11may be moved after the dish mounting portion22has been fixed. This makes it possible to omit the fifth driving mechanism35, for example, since rotation of the dish mounting portion22is not required.

Furthermore, when performing the dispensing operation, for example, the nozzle11of the syringe1may be initially directed to the second area illustrated inFIG. 9(area in the vicinity of the lowermost part in the ring-shaped area in which the inner bottom surface of the tilted dish5is in contact with the inner side surface thereof), and then is direct around along the ring-shaped area in which the inner bottom surface of the dish5is in contact with the inner side surface thereof. This makes it possible to omit the fifth driving mechanism35, for example, since rotation of the dish mounting portion22is not required.

The above embodiments of the present invention are simply for facilitating the understanding of the present invention and are not in any way to be construed as limiting the present invention. The present invention may variously be changed or altered without departing from its spirit and encompass equivalents thereof.