Patent Publication Number: US-2018037860-A1

Title: Liquid transferring apparatus and liquid transferring method

Description:
TECHNICAL FIELD 
     The technical field relates to a liquid transferring apparatus and a liquid transferring method. 
     BACKGROUND 
     A related art liquid transferring apparatus used in cell culture includes a piston actuated by a motor to move a flange of a syringe for sucking/injecting a liquid from a gripped container (see Japanese Patent Examined Publication No. 6-34825). 
       FIG. 11  is a view illustrating a liquid transferring apparatus of the related art disclosed in Japanese Patent Examined Publication No. 6-34825. 
     In  FIG. 11 , cylinder  3  of syringe  2  is set on lower support member  11  provided on base  1 , and cylinder  3  of syringe  2  is fixed by upper support member  12 , while flange portion  5   a  of piston  5  is set on pushing member  6 . 
     Pushing member  6  is fixed to movable block  17 , and advances/retracts together with movable block  17  by movable block  17  advancing/retracting by actuation of motor  16 . Accordingly, since pushing member  6  is actuated so as to push/pull up set piston  5  to/from cylinder  3 , suction/injection of liquid is realized. 
     SUMMARY 
     However, in the configuration of the related art, since flange portion  5   a  of piston  5  can be attached to/removed from pushing member  6 , a gap is always generated between flange portion  5   a  and a portion sandwiching flange portion  5   a.  As a result, there is a problem that the gap affects the accuracy of the amount of liquid to be sucked/injected. 
     For example, in a case where a syringe sucks up 3 ml of liquid when piston  5  is pulled up by 50 mm from a pushed in state and the syringe injects liquid after sucking up liquid, if a gap of 0.1 mm is generated between (between  5   a  and  6   a ) flange portion  5   a  of piston  5  and a portion of pushing member  6  in which flange portion  5   a  is sandwiched, by calculation, an error of 3 ml÷50 mm×0.1 mm=0.006 ml (6 μl) is generated in the amount of liquid to be injected. 
     In view of the above problem, as well as other concerns, a liquid transferring apparatus and a liquid transferring method which is preferably used in a cell culture apparatus, eliminates an error caused by a gap existing between a flange portion of a piston and a portion sandwiching the flange portion of the related art, and liquid can be sucked up/injected with high liquid quantity accuracy. 
     In order to achieve the object described above, according to main aspect of the disclosure, in a cell culture apparatus which sucks up or discharges a liquid by moving a piston of a syringe vertically, there is provided a liquid transferring apparatus including a first motor which actuates the piston by supporting a flange pulling-up portion to be vertically movable and by pulling up a flange portion of the piston from below via the flange pulling-up portion; a second motor which supports a flange pushing portion to be vertically movable and actuates the piston so as to push the flange portion of the piston from above via the flange pushing portion; a cylinder fixing portion which fixes a cylinder of the syringe; and a mechanical frame which supports the first motor, the second motor, and the cylinder fixing portion. 
     In the liquid transferring apparatus, when liquid is sucked up, the second motor is actuated in a direction in which liquid is sucked up by a stroke amount corresponding to an amount of liquid to be sucked up and then the first motor is also actuated in a direction in which liquid is sucked up until the flange pulling-up portion is hit against the flange portion and is stopped. Further, when liquid is injected, the first motor is actuated in a direction in which liquid is injected by a stroke amount corresponding to an amount of liquid to be injected and then the second motor is also actuated in a direction in which liquid is injected until the flange pushing portion is hit against the flange portion and is stopped. 
     As described above, according to the liquid transferring apparatus provided in the cell culture apparatus of the disclosure, since gaps between the flange portion and the flange pulling-up portion and between the flange portion and the flange pushing portion can be eliminated at the time of liquid suction/injection, suction/injection of liquid can be performed with high accuracy. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1A  is a front view illustrating a liquid transferring apparatus according to an embodiment of the disclosure. 
         FIG. 1B . is a side view illustrating the liquid transferring apparatus according to the embodiment of the disclosure. 
         FIG. 2  is a view illustrating a positional relationship between a syringe and a motor. 
         FIG. 3A  is a view illustrating a state where a claw of a cylinder fixing portion is opened. 
         FIG. 3B  is a view illustrating a state where a cylinder is fixed by the claw of the cylinder fixing portion being closed. 
         FIG. 4  is a view illustrating a state where the piston is pushed into the cylinder. 
         FIG. 5  is a view illustrating a state in which the piston is pushed into the cylinder to a tip thereof and the flange portion is sandwiched between the flange pulling-up portion and the flange pushing portion without any gap. 
         FIG. 6  is a view illustrating a state where the second motor is actuated to a side opposite to the tip of the cylinder by a stroke amount corresponding to an amount of liquid to be sucked up. 
         FIG. 7  is a view illustrating a state in which the flange pulling-up portion is in contact with the flange portion, the flange pushing portion and the flange portion are sandwiched between each other without any gap, and a first motor is stopped. 
         FIG. 8  is a view illustrating a state where the first motor is actuated to a tip side of the cylinder by a stroke amount corresponding to an amount of liquid to be injected. 
         FIG. 9  is a view illustrating a state in which the flange pushing portion is in contact with the flange portion, the flange pulling-up portion and the flange portion are sandwiched with each other without any gap, and the second motor is stopped. 
         FIG. 10  is a view illustrating a state in which all the liquid in the cylinder is discharged. 
         FIG. 11  is a view illustrating a structure of a liquid suction/injection mechanism of the related art. 
     
    
    
     DESCRIPTION OF EMBODIMENTS 
     Hereinafter, embodiment of the disclosure will be described with reference to the drawings. 
     Embodiment 
       FIG. 1A  is a front view illustrating a liquid transferring apparatus which is provided in a cell culture apparatus according to an embodiment of the disclosure, and  FIG. 1B  is a side view thereof. 
     The cell culture apparatus includes first motor  52 , second motor  53 , syringe  61 , flange pulling-up portion  54 , flange pushing portion  55 , cylinder fixing portion  56 , and mechanical frame  51 , as a liquid transferring apparatus. 
     Mechanical frame  51  is a base member which supports and fixes syringe  61  (cylinder fixing portion  56 ), first motor  52 , and second motor  53 . 
     Syringe  61  includes cylinder  62  and piston  63  which is actuated in cylinder  62 . Further, flange portion  63   a  is provided at an upper end of piston  63  of syringe  61 . Piston.  63  is vertically actuated by power being transferred to flange portion  63   a  via flange pulling-up portion  54  or flange pushing portion  55 . 
     First motor  52  supports flange pulling-up portion  54  to be vertically movable and actuates piston  63  so as to pull up flange portion  63   a  of piston  63  from below via flange pulling-up portion  54 . 
     Second motor  53  supports flange pushing portion  55  to be vertically movable and actuates piston  63  so as to push flange portion  63   a  of piston  63  from above via flange pushing portion  35 . 
     In addition, first motor  52  and second motor  53  are, for example, linear motors, which are driven by a driving power supplied by a control device (not illustrated) provided outside. 
     Here, flange pulling-up portion  54  includes a flat surface on an upper surface thereof. When flange pulling-up portion  54  is moved by first motor  52 , the upper surface of flange pulling-up portion  54  abuts against a lower surface of flange portion  63   a  of piston  63  so as to be in close contact therewith. 
     Further, flange pushing portion  55  includes a flat surface on the lower surface. When flange pushing portion  55  is moved by second motor  53 , the lower surface of flange pushing portion  55  abuts against an upper surface of flange portion  63   a  of piston  63  so as to be in close contact therewith. 
     Mechanical frame  51  has, for example, an L-shaped external shape. For example, mechanical frame  51  is disposed so that first surface  51   a  and second surface  51   b  between which an intersect ion line extends along the vertical direction and which are orthogonal to each other are formed. 
     In  FIG. 1A , first motor  52  is attached to first surfaces  51   a  of one side of mechanical frame  51  and second motor  53  is attached to second surface  51   b  of one side of mechanical frame  51  which forms an angle of 90 degrees with first surface  51   a.    
     Although first motor  52  and second motor  53  can also be configured by motors which change a rotational motion into a linear motion using the screw shaft as shown in  FIG. 11  which explains an example of related art, a linear motor using a permanent magnet and an electromagnetic coil is preferable because the linear motor can be made thinner and a main body of the liquid transferring apparatus can be miniaturized. 
     In addition, syringe  61  is attached to mechanical frame  51  via cylinder fixing portion  56  which fixes cylinder  62 . In the present embodiment, cylinder fixing portion  56  is attached to same second surface  51   b  as second motor  53 . In addition, cylinder fixing portion  56  can be attached to same first surface  51   a  as first motor  52 . 
     With the liquid transferring apparatus, syringe  61  is mounted, liquid is sucked up/injected, the residual liquid is discharged, and syringe  61  is removed in the following order. 
     First, syringe  61  is mounted in the following order. 
     When syringe  61  is mounted on mechanical frame  51 , the upper and lower surfaces of flange portion  63   a  are disposed between the lower surface of flange pushing portion  55  and the upper surface of flange pulling-up portion  54 . At this time, first, first motor  52  and second motor  53  are actuated so that the gap between the upper surface of flange pulling-up portion  54  and the lower surface of flange pushing portion  55  is equal to or more than the width of flange portion  63   a.    
     More preferably, as illustrated in  FIG. 2 , in order to facilitate mounting of syringe  61 , flange pulling-up portion  54  is moved to a position of lower limit  52 D and first motor  52  and second motor  53  are actuated in order to move flange pushing portion  55  to a position of upper limit  53 U. 
     After syringe  61  is positioned with respect to mechanical frame  51 , cylinder  62  is fixed by cylinder fixing portion  56  ( FIG. 3A  and  FIG. 3B ). Generally, cylinder  62  has collar  62   a  having a circular width at an end opposite to the tip thereof. In the embodiment, collar  62   a  is inserted and sandwiched in the groove of claws  56   a  and  56   b  by collar  62   a  of cylinder  62  being closed by claws  56   a  and  56   b  provided with grooves in the laterally direction. Accordingly, cylinder  62  is fixed to cylinder fixing portion  56  and thus syringe  61  is mounted. 
     The suction of the liquid fay syringe  61  is performed in the following order. 
     First, second motor  53  is actuated to move flange pushing portion  55  toward the tip side of cylinder  62  . At this time, the lower surface of flange pushing portion  55  is in contact with the upper surface of flange portion  63   a  and pushes flange portion  63   a,  and thus piston  63  is stopped in a state of being pushed into cylinder  62  to the tip thereof ( FIG. 4 ). 
     Next, first motor  52  is actuated to move flange pulling-up portion  54  toward a side opposite to the tip of cylinder  62  ( FIG. 5 ). At this time, the upper surface of flange pulling-up portion  54  is in contact with the lower surface of flange portion  63   a  and pulls up flange portion  63   a  and thus piston  63  is pulled up. 
     However, in  FIG. 5 , when flange pulling-up portion  54  is moved toward a side opposite to the tip of cylinder  62  by first motor  52 , torque is applied from second motor  53  to flange pushing portion  55 . For example, when flange pulling-up portion  54  is moved, static torque is applied from second motor  53  to flange pushing portion  55 . At this time, the torque amount [N·m] applied to flange pulling-up portion  54  by first motor  52  is set to be less than the torque amount [N·m] applied to flange pushing portion  55  by second motor  53 . Accordingly, the piston  63  is pushed into cylinder  62  to the tip thereof and flange portion  63   a  is sandwiched between flange pulling-up portion  54  and flange pushing portion  55  without any gap. 
     In this state, the tip of cylinder  62  is immersed into liquid  71  to be sucked up and first, flange pushing portion  55  is moved to a side opposite to the tip of cylinder  62  by the stroke amount corresponding to the amount of liquid to be sucked, by second motor  53  ( FIG. 6 ). 
     Thereafter, by actuation of first motor  52 , flange pulling-up portion  54  is moved to a side opposite to the tip of cylinder  62  ( FIG. 7 ). Flange pulling-up portion  54  is moved until being pushed by flange portion  63   a  and stopped. By the actuation of first motor  52 , flange pulling-up portion  54  pulls up flange portion  63   a  and piston  63  and the liquid is sucked up into cylinder  62 . 
     In  FIG. 7 , however, when flange pulling-up portion  54  is moved to a side opposite to the tip of cylinder  62  by first motor  52 , torque is applied from second motor  53  to flange pushing portion  55 . For example, when flange pulling-up portion  54  is moved, static torque is applied from second motor  53  to flange pushing portion  55 . At this time, the torque amount [N·m] applied to flange pulling-up portion  54  by first motor  52  is desirably set to be less than the torque amount [N·m] applied to flange pushing portion  55  by second motor  53 . According to this, flange pulling-up portion  54  is stopped in a state of being in contact with flange portion  63   a  pushed by the flange pushing portion  55 . 
     Accordingly, flange portion  63   a  is sandwiched between flange pulling-up portion  54  and flange pushing portion  55  without any gap. Thus, the error of the liquid amount due to the gap which is the problem of the example of the related art can be eliminated, and thus liquid can be sucked up with high accuracy. 
     The injection of the liquid by syringe  61  is performed in the following order. 
     In a case where the sucked liquid is injected, first motor  52  is actuated to move flange pulling-up portion  54  to the tip side of cylinder  62  by the stroke amount corresponding to the amount of liquid to be injected ( FIG. 8 ). 
     Thereafter, by the actuation of second motor  53 , flange pushing portion  55  is moved to the tip side of cylinder  62  ( FIG. 9 ). Flange pushing portion  55  is moved until being pushed by flange portion  63   a  and stopped. By the actuation of second motor  53 , flange pushing portion  55  pushes down flange portion  63   a  and piston  63  and the liquid is injected. 
     However, in  FIG. 9 , when flange pushing portion  55  is moved to the tip side of cylinder  62  by second motor  53 , torque is applied from first motor  52  to flange pulling-up portion  54 . For example, when flange pushing portion  55  is moved, static torque is applied from first motor  52  to flange pulling-up portion.  54 . At this time, the torque amount [N·m] which is applied to flange pushing portion  55  by second motor  53  is desirably set to be less than the torque amount [N·m] which is applied to flange pulling-up portion  54  by first motor  52 . According to this, flange pushing portion  55  is stopped in a state of being in contact with flange portion  63   a  supported by flange pulling-up portion  54 . 
     Accordingly, flange portion  63   a  is sandwiched between flange pulling-up portion  54  and flange pushing portion  55  without any gap. Thus, the error of the liquid amount due to the gap which is the problem of the example of the related art can be eliminated, and thus liquid can be sucked up with high accuracy. 
     After the desired injection is completed, the discharge of the residual liquid remaining in cylinder  62  is performed in the following order. 
     When all the liquid in cylinder  62  is discharged, excitation of first motor  52  is cut off and second motor  53  is actuated by torque control toward the tip of cylinder  62 . In a state where piston  63  is pushed into cylinder  62  to the tip thereof, although second motor  53  is stopped, it is possible to set a state where all of the liquid in cylinder  62  is discharged ( FIG. 10 ). 
     Finally, syringe  61  is removed in the following order. 
     In a case where syringe  61  is removed, in the positions of first motor  52  and second motor  53 , when the gap between flange pulling-up portion  54  and flange pushing portion  55  is equal to or more than the width of flange portion  63   a,  although syringe  61  can be removed, in order to facilitate the removal, it is preferable to position flange pulling-up portion  54  at lower limit  52 D and flange pushing portion  55  at upper limit  53 U. This is the same as when being mounted. 
     Simultaneously, the fixing of cylinder  62  fixed by cylinder fixing portion  56  is released. By opening claws  56   a  and  56   b  which sandwich collar  62   a  of cylinder  62 , the fixing of the cylinder is released and becomes a state of being removable. 
     The cell culture apparatus including the liquid transferring apparatus described herein can be used in a process which is referred to as medium exchange. 
     Although cells are cultured in a culture container such as a dish or a well plate filled with a medium which is culture liquid, the medium needs to be replaced within a certain period of time, and the medium exchange is a process which sucks up the old medium in the culture container, discards the old medium and injects fresh medium. 
     In the cell culture apparatus provided with the liquid transferring apparatus of the disclosure, medium exchange can be performed in the following order. 
     First, syringe  61  is mounted on the liquid transferring apparatus, after being mounted, the liquid transferring apparatus is moved so that the tip of syringe  61  is immersed into the medium of the culture container, and the medium is sucked up. For the dish and the well plate, since recommended amount of injection liquid is defined and the amount of liquid which is injected is determined in advance, the recommended amount is referred to as an amount of liquid to be sucked up. 
     After the sucking up is completed, the liquid transferring apparatus is moved from the culture container, piston  63  is pushed into cylinder  62 , and the sucked up medium is discarded in a state of being all discharged. Thereafter, syringe  61  is removed from the liquid transferring apparatus. 
     Next, new syringe  61  is mounted on the liquid transferring apparatus. The purpose of replacing syringe  61  is to prevent contamination. 
     After new syringe  61  is mounted, the liquid, transferring apparatus is moved so that the tip of syringe  61  is immersed into fresh medium and the medium is sucked up. As described above, for the dish and the well plate, since the recommended amount of injection liquid is defined and the amount of liquid to be injected is determined, the amount of liquid to be injected is referred to as an amount of liquid to be sucked up. 
     After suction of the fresh medium, the liquid transferring apparatus is moved so that a fresh medium is injected into the culture container and injects the amount of liquid described above. 
     The liquid transferring apparatus is moved from the culture container, piston  63  is pushed in cylinder  62 , all the remaining medium is discharged and thus the remaining medium is discarded and thereafter syringe  61  is removed from the liquid transferring apparatus. 
     As described above, although specific example of the disclosure is described in detail, the example is merely an example and does not limit the scope of the claims. Techniques described in the claims include those in which the specific example exemplified above is variously modified and changed. 
     Since the liquid transferring apparatus provided in the cell culture apparatus of the disclosure can eliminate the gap between the flange and the flange pulling-up portion or the flange pushing portion at the time of liquid suction/injection, the error of the liquid amount due to the gap which is the problem of the example of the related art can be eliminated, liquid suction/injection can be performed with high accuracy, and thus the liquid transferring apparatus can be also applied to the application of cell culture process automation.