Abstract:
A liquid dispensing device. The liquid dispensing device has a tray for holding a liquid at a relatively constant level. A syringe is used for drawing fluid from the tray. A liquid container containing a liquid is positioned upside-down in the tray such that the opening of the liquid container defines a vertical position that is slightly below the liquid level in the tray. Atmospheric pressure on the liquid in the tray and a vacuum inside the liquid container prevents liquid from draining from the container until the fluid level in the tray drops to a level approximately equal to the vertical position of the opening. The positioning of the syringe for drawing fluid is simplified by reason of the fact that the level of fluid in the tray is maintained at an approximately constant level despite withdrawal of quantities of fluid from the tray.

Description:
[0001]     The present invention relates to liquid handling devices, and in particular, to liquid dispensing devices.  
       BACKGROUND OF THE INVENTION  
       [0002]     Chemical solutions may be mixed either manually by a chemist or laboratory technician or they may be mixed automatically by an automated liquid mixing device. A syringe (also known as a pipette, pipettor or a micropipettor) may be used to transfer liquid from a bottle to a location where liquids are mixed, such as a micro-well plate.  
         [0003]     For example,  FIG. 1A  shows prior art syringe  5  positioned over bottle  1 B containing a liquid. In  FIG. 1B , a technician has immersed the tip of syringe  5  into the liquid in bottle  1 B. In  FIG. 1C , the technician has pulled upward on plunger  6  with one hand while holding the bottom part of syringe  5  down with the other hand. Pulling upward on plunger  6  draws liquid into syringe  5 . Syringe  5  can now be used for liquid dispensing.  
         [0004]     There are problems with the prior art method of liquid dispensing illustrated in  FIGS. 1A-1C . To draw liquid into the syringe it is only necessary to slightly immerse the tip of the syringe below the level of the liquid surface, as shown in  FIG. 1D . However, a technician will typically over-immerse the syringe into the liquid. For example, as shown in  FIG. 1C , the end of syringe  5  has been immersed far below the surface of the liquid in bottle  1 B. As a result, after syringe  5  is removed from the liquid in bottle  1 B, there will be an unnecessarily large amount of liquid adhered to the outside surface of syringe  5 . This liquid can drip off, causing a mess and possibly causing contamination in the laboratory.  
         [0005]     There are also similar problems with prior art automated liquid mixing devices. As with the manual method, prior art automated pipettors are ineffective at placing the syringe at the optimum level inside bottle  1 B to prevent unnecessary liquid adhesion to the outside surface of syringe  5 . The challenge for the prior art automated systems has been that as liquid is gradually removed from its bottle, the surface level of the liquid inside the bottle gradually decreases. Prior art systems have been unsuccessful in adjusting the degree to which the syringe is inserted into the bottle to appropriately account for the varying amount of liquid inside the bottle.  
         [0006]     What is needed is a better liquid dispensing device.  
       SUMMARY OF THE INVENTION  
       [0007]     The present invention provides a liquid dispensing device. The liquid dispensing device has a tray for holding a liquid at a relatively constant level. A syringe is used for drawing fluid from the tray. A liquid container containing a liquid is positioned upside-down in the tray such that the opening of the liquid container defines a vertical position that is equal to or just slightly below the liquid level in the tray. Atmospheric pressure on the liquid in the tray and a vacuum inside the liquid container prevents liquid from draining from the container until the fluid level in the tray drops to a level just below the vertical position of the opening. The positioning of the syringe for drawing fluid is simplified in that the level of fluid in the tray is maintained at an approximately constant level despite withdrawal of quantities of fluid from the tray. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0008]      FIGS. 1A-1D  show prior art methods for dispensing liquid from a bottle.  
         [0009]      FIG. 2A  shows a detailed perspective view of a first preferred embodiment of the present invention.  
         [0010]      FIG. 2B  shows a detailed exploded perspective view of a first preferred embodiment of the present invention.  
         [0011]      FIGS. 3 and 4  show a simplified front view and exploded view, respectively, of the first preferred embodiment.  
         [0012]      FIGS. 5-12  show the operation of the first preferred embodiment of the present invention.  
         [0013]      FIGS. 13A-16C  show a second preferred embodiment of the present invention.  
         [0014]      FIG. 17  shows a perspective view of a third preferred embodiment of the present invention.  
         [0015]      FIGS. 18-42  show the operation of the third preferred embodiment of the present invention.  
         [0016]      FIGS. 43-44  show the utilization of locating indentations. 
     
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS  
       [0017]     In a preferred embodiment of the present invention, tray  3  ( FIG. 8 ) maintains an approximately constant dispensing level equal to or slightly above opening  1 A of bottle  1  for syringe  5  as liquid is dispensed out of tray  3  (see  FIGS. 9-11 ). By maintaining an approximately constant dispensing level, a laboratory technician or an automated dispensing device can more effectively and with less mess and error remove liquid from tray  3 .  
       Manual Dispensing  
     First Preferred Embodiment  
     Liquid Dispenser  
       [0018]      FIG. 2A  shows a detailed perspective view and  FIG. 2B  shows a detailed exploded perspective view of liquid dispenser  3 D. Likewise,  FIGS. 3 and 4  show a simplified front view and exploded view, respectively, of liquid dispenser  3 D.  
         [0019]     In the first preferred embodiment, liquid to be dispensed is contained in upside-down bottle  1 . As shown in  FIG. 8 , upside-down bottle  1  is held in place on top of tray  3  via metal bottle retaining clip  4 . Preferably, tray  3  is fabricated from clear plastic. In the first preferred embodiment, a controlled amount of liquid flows out of bottle  1  and enters tray  3  where it is maintained inside tray  3  at an approximately constant level equal to or just slightly above the level of the level of the opening of bottle  1  as shown at  1 A in  FIG. 9 . The liquid can then be easily removed by syringe  5  for further dispensing.  
       Operation of the First Preferred Embodiment  
       [0020]     Prior to attaching bottle  1  to tray  3 , bottle  1  is filled with liquid to be dispensed.  FIG. 5  shows a side view of bottle  1  containing liquid.  
         [0021]     In  FIG. 6 , tray  3  has been snap-fitted on top of bottle  1 . Bottle  1  is preferably held in place via metal retaining clip  4  (also shown in more detail in  FIG. 2A ).  
         [0022]     In  FIG. 7 , tray  3  and bottle  1  have been flipped over so bottle  1  is upside-down. A portion of the liquid that was in bottle  1  has flowed out of bottle  1  and into tray  3 . The liquid will continue to flow out of bottle  1  until the level of liquid inside tray  3  is equal to or just slightly above the level of opening  1 A of bottle  1 . The combined effects of 1) atmospheric pressure exerting its force onto the surface of the liquid inside tray  3  and 2) the vacuum formed inside bottle  1  counter the effects of gravity and function to prevent the remainder of the liquid inside bottle  1  from emptying.  
         [0023]     In  FIG. 8 , syringe  5  has been inserted into syringe holder  8  of tray  3 . Syringe holder  8  includes abutment  8 A (as shown in  FIG. 4  and  FIG. 7 ). Abutment  8 A prevents further downward movement of syringe  5  and controls the location of tip  5 A of syringe  5  so that tip  5 A extends below the surface of the liquid inside tray  3  to a position just above the level of tilted bottom component  9  as shown in  FIG. 8  (see also  FIG. 3 ).  
         [0024]     In  FIG. 9 , a user has grabbed syringe plunger  6  with one hand and has pulled it upward while holding syringe body  5 B down with the other hand. The upward movement of syringe plunger  6  has caused liquid from tray  3  to be drawn up inside syringe  5 . As liquid is drawn up inside syringe body  5 B, the surface level of the liquid inside tray  3  decreases until eventually the level is below the level of opening  1 A. Air is able to enter tray  3  via air filter  7 . As the surface level decreases below the level of opening  1 A, the vacuum inside bottle  1  will be momentarily broken as air is able to enter bottle  1  and flow upward as air bubbles through the liquid in bottle  1 . As the air bubbles are flowing upward, liquid inside bottle  1  is filling tray  3 . Liquid will continue to flow out of bottle  1  until once again the level of liquid inside tray  3  is equal to or slightly above the level of opening  1 A of bottle  1 , sealing off opening  1 A and allowing the vacuum inside bottle  1  to reestablish.  
         [0025]     In this fashion, liquid can be removed from tray  3  by syringe  5 . After liquid has been removed from tray  3  via syringe  5 , the user utilizes syringe  5  to deposit the removed liquid into a liquid receptacle device. For example in the first preferred embodiment, utilizing syringe  5 , the user transfers liquid from tray  3  to a well in a micro-well plate.  
         [0026]     While liquid is being removed, tray  3  maintains the level of the liquid inside tray  3  at a level equal to or just slightly above the level of opening  1 A of bottle  1 . For example, in  FIG. 10 a  user utilizing syringe  5  has removed a significant amount of liquid from tray  3  so that the level of liquid inside bottle  1  has decreased to level much lower than that shown in  FIG. 9 . However, the level inside tray  3  will rise until it is equal to or just slightly above the level of opening  1 A. In  FIG. 11 , the user has removed even more of the liquid from tray  3  so that bottle  1  is approximately empty. The level of the liquid inside tray  3  is approximately equal to the level of opening  1 A.  
         [0027]     In  FIG. 12 , even more liquid has been removed from tray  3 . After all the liquid has been removed from bottle  1 , the user continues to remove liquid from tray  3 , causing the level of the liquid to go below that of opening  1 A. Tilted bottom component  9  has caused the remaining liquid inside tray  3  to puddle below the area of syringe  5  so that liquid can still be easily removed.  
       Second Preferred Embodiment  
       [0028]     A second preferred embodiment is shown in  FIGS. 13A and 13B . In the second preferred embodiment, tray  23  includes liquid level indicator  24 . Below liquid level indicator is black tape strip  27 . A detailed perspective view of liquid level indicator  24  is shown in  FIG. 14 . In the second preferred embodiment, liquid level indicator  24  is fabricated from clear plastic. Preferably, liquid level indicator  24  includes both low level indicator  25  and high level indicator  26 .  
       Operation of the Second Preferred Embodiment  
       [0029]     In  FIG. 13A , liquid tray  23  is empty. This will cause light rays entering liquid level indicator  24  to be totally internally reflected as shown in  FIG. 13C . Therefore, a user looking down onto the top of tray  23  will see that both low level indicator  25  and high level indicator  26  of liquid indicator  24  appear to be whitish, as shown in  FIG. 13B .  
         [0030]     In  FIG. 15A , liquid tray  23  is filled so that the level of the liquid in tray  23  is slightly above the level of opening  1 A. As explained above in reference to the first preferred embodiment, the preferred level of the liquid in tray  23  is equal to or just slightly above the level of opening  1 A. In  FIG. 15A , the pointed tip of low level indicator  25  is submerged in the liquid in tray  23  and the pointed tip of high level indicator  26  is above the liquid in tray  23 . Because the pointed tip of low level indicator is submerged, light rays entering low level indicator  25  will be refracted as shown in  FIG. 15C  so that they will be partially absorbed and partially reflected by black tape strip  27 . Conversely, because the pointed tip of high level indicator  26  is above the liquid in tray  3 , light rays entering high level indicator  26  will be totally internally reflected. Therefore, a user looking down onto the top of tray  23  will see that low level indicator  25  appears to be black and that high level indicator  26  appears to be whitish, as shown in  FIG. 15B .  
         [0031]     Although liquid tray  23  functions to keep the level of liquid inside tray  23  at a level equal to or just slightly above opening  1 A as shown in  FIG. 15A , the level inside tray  23  can rise to a higher level if, for example, tray  23  is inadvertently bumped or tilted breaking the vacuum inside bottle  1  and allowing air to enter bottle  1 . In  FIG. 16A , liquid tray  23  is filled so that the level of the liquid in tray  23  is above the level of high level indicator  26 . The pointed tips of both low level indicator  25  and high level indicator  26  are submerged in the liquid in tray  23 . Because the pointed tips of both level indicators are submerged, light rays entering level indicators  25  and  26  will be refracted as shown in  FIG. 16C  so that they will be partially absorbed and partially reflected by black tape strip  27 . Therefore, a user looking down onto the top of tray  23  will see that low level indicator  25  and high level indicator  26  appear to be black, as shown in  FIG. 16B .  
       Automated Liquid Handling Device  
     Third Preferred Embodiment  
       [0032]     A third preferred embodiment is shown in FIGS.  17  to  42 . In the third preferred embodiment an array of liquid dispensers similar to the dispensers described above are situated on platform  30  ( FIG. 17 ). Computer  32  is programmed to automatically position robotic syringe grabber  31  over a selected liquid dispenser. Robotic syringe grabber  31  then automatically grabs syringe  5  from the selected liquid dispenser and draws liquid into the syringe in a fashion similar to that described above in reference to earlier preferred embodiments. Because the liquid dispensers situated on platform  30  maintain the level of the liquid to be dispensed at an approximately constant level. Syringe  5  is positioned so that its tip is submerged an optimum distance into the liquid to be dispensed. Therefore, robotic syringe grabber  31  does not have to be programmed to account for varying liquid levels. Robotic syringe grabber  31  then transfers the liquid to a liquid receiving device (such as micro-well plate  33 A) where the liquid is dispensed.  
       Example of Operation of Third Preferred Embodiment  
       [0033]     A detailed perspective view of the third preferred embodiment is shown in  FIG. 17 . A top view and left side view is shown in  FIGS. 18 and 19 , respectively. Dispensers  3   a   1 - 3   e   10  and micro-well plates  33   a - 33   e  are arranged on platform  30 . Dispensers  3   a   1 - 3   e   10  are each similar to liquid dispenser  3 D described above. Robotic syringe grabber  31  is controlled by computer  32 . In the third preferred embodiment, computer  32  is programmed to control robotic syringe grabber  31  to draw liquid into syringes  5  of the selected dispensers. Robotic syringe grabber  31  is then controlled by computer  32  to remove syringes  5  from the selected dispensers and transfer the liquid in the syringe to pre-selected micro-well plates.  
         [0034]     In the following example, computer  32  is programmed to control robotic syringe grabber  31  to remove syringe  5  located in dispenser  3   b   7  and transfer the liquid to micro-well plate  33   a.    
         [0035]     In  FIGS. 20 and 21 , linear actuators  40  and  41  have been controlled by computer  32  to position robotic syringe grabber  31  over dispenser  3   b   7 . Linear actuators  40  and  41  are preferably belt-driven linear actuators. Motor  42  has turned wheel  43  clockwise. The clockwise motion of wheel  43  has caused belt  46 , wheel  44  and belt  45  to also turn clockwise. The clockwise motion of belt  45  has caused linear actuator  40  to move to the right ( FIG. 21 ) so that linear actuator  40  is just above the row of dispensers having dispenser  3   b   7  ( FIG. 20 ). Concurrently, motor  47  of linear actuator  40  has turned wheel  48  clockwise causing belt  49  to turn clockwise. The clockwise motion of belt  49  has caused robotic syringe grabber  31  to move to the left ( FIG. 20 ) so that it is positioned above dispenser  3   b   7 .  
         [0036]      FIG. 22  shows a front view of robotic syringe grabber  31  positioned over dispenser  3   b   7 . Gripper  50  is positioned slightly to the left of the vertical center of dispenser  3   b   7 .  
         [0037]     In  FIG. 23  motor  51  has controlled linkage  52  so that it has pulled upward on syringe gripper arm  53  of syringe gripper  50  causing syringe gripper arm  53  to turn counterclockwise about axis  58 . The counterclockwise motion of syringe gripper arm  53  has pushed syringe plunger arm  54  counterclockwise about axis  59  compressing linear spring  57 . The counterclockwise rotations of syringe gripper  50  and plunger gripper  55  have exposed plunger foot  56 . Sensor  70  verifies that syringe gripper  50  is open and sensor  71  verifies that plunger gripper  55  is open.  
         [0038]     In  FIG. 24 a  linear actuator motor (not shown) of linear actuator  60  has turned screw  62  of robotic syringe gripper  31  causing platform  61  to move downward on track  63  of linear actuator  60 . Platform  61  has moved downward until plunger foot  56  has contacted plunger  6 . Plunger present sensor  64  verifies that plunger foot  56  has contacted plunger  6 .  
         [0039]     In  FIG. 25  computer  32  has moved robotic syringe gripper  31  slightly to the right so that fixed syringe gripper jaw  50   a  and fixed plunger gripper jaw  55   a  engage syringe  5  and plunger  6 , respectively.  
         [0040]     In  FIG. 26  motor  51  has controlled linkage  52  so that it has lowered syringe gripper arm  53  of syringe gripper  50  causing syringe gripper arm  53  to turn clockwise. The clockwise motion of syringe gripper arm  53  has allowed linear spring  57  to push syringe plunger arm  54  clockwise. The clockwise rotations of syringe gripper arm  53  and syringe plunger arm  54  have caused syringe gripper jaw  50   b  and plunger gripper jaw  55   b  to engage syringe  5  and plunger  6 , respectively. Sensor  70  verifies that syringe gripper  50  is closed and not jammed and sensor  71  verifies that plunger gripper  55  is closed and not jammed.  
         [0041]     In  FIG. 27  plunger motor  65  has raised plunger gripper  55  as shown. A rear perspective view of plunger motor  65  and plunger gripper  55  is shown in  FIG. 27B . Plunger gripper  55  is gripping plunger  6 . Therefore, plunger  6  has also been raised. The raising of plunger  6  has drawn liquid from dispenser  3   b   7  ( FIG. 27 ) inside syringe  5  in a fashion similar to that described above in reference to  FIG. 9 . While liquid is being drawn into syringe  5 , the force on plunger  6  is monitored by sensor  72 . If the force is outside of acceptable parameters, a warning will be displayed. If the pressure is too low, the plunger may be drawing in air along with the liquid. If the pressure is too high, there may be an obstruction blocking the tip of the plunger.  
         [0042]     In  FIG. 28  linear actuator  60  has raised platform  61  so that syringe  5  is at sufficient height to clear dispenser  3   b   7 .  
         [0043]     In  FIGS. 29 and 30  linear actuators  40  and  41  have been controlled by computer  32  to position robotic syringe grabber  31  over micro-well plate  33   a.    
         [0044]      FIG. 31  shows a side view of robotic syringe grabber  31  holding syringe  5  so that it is positioned over well  33   a   1  of micro-well plate  33   a.    
         [0045]     In  FIG. 32  linear actuator  60  has lowered platform  61  so that tip  5   a  of syringe  5  is positioned at a position just above the top of well  33   a   1 .  
         [0046]     In  FIG. 33  plunger motor  65  has lowered plunger gripper  55  causing plunger  6  to be pressed downward. Again, the force on plunger  6  has been monitored by sensor  72 . Actuator  73  has been momentarily activated to cause its core rod to bump the top of plunger gripper  55 . The repeated bumping has generated shock waves that have been transmitted through plunger gripper  55  to plunger  6  and to syringe  5 . The shock waves serve to dislodge any drops that may be adhering to the tip of syringe  5 . As shown in  FIG. 33 , a small amount of liquid has been dispensed into well  33   a   1 .  
         [0047]     In  FIG. 34  linear actuator  40  ( FIG. 29 ) has moved robotic syringe grabber  31  slightly to the right so that syringe  5  is positioned above well  33   a   2 . Plunger motor  65  has further lowered plunger gripper  55  causing plunger  6  to be pressed downward. Actuator  73  has been activated. A small amount of liquid has been dispensed into well  33   a   2 .  
         [0048]      FIG. 35  shows syringe  5  positioned above well  33   a   8 . In a fashion similar to that described in reference to  FIGS. 33 and 34 , small amounts of liquid have been dispensed in wells  33   a   3 - 33   a   8 .  
         [0049]     In  FIG. 36  linear actuator  60  has raised platform  61 .  
         [0050]     In  FIG. 37 , linear actuators  40  and  41  have positioned robotic syringe grabber  31  over dispenser  3   b   7  (see also  FIGS. 20 and 21 ).  
         [0051]     In  FIG. 38  linear actuator  60  has lowered platform  61  so that syringe  5  is inside dispenser  3   b   7 .  
         [0052]     In  FIG. 39  plunger motor  65  has lowered plunger gripper  55  causing plunger  6  to be pressed downward. The remaining amount of liquid inside syringe  5  has been returned to dispenser  3   b   7 .  
         [0053]     In  FIG. 40  motor  51  has controlled linkage  52  so that it has pulled upward on syringe gripper arm  53  of syringe gripper  50  causing syringe gripper arm  53  to turn counterclockwise about axis  58 . The counterclockwise motion of syringe gripper arm  53  has pushed syringe plunger arm  54  counterclockwise about axis  59  compressing linear spring  57 . The counterclockwise rotations of syringe gripper  50  and plunger gripper  55  have exposed plunger foot  56 . Sensor  70  verifies that syringe gripper  50  is open and sensor  71  verifies that plunger gripper  55  is open.  
         [0054]     In  FIG. 41  linear actuator  40  ( FIG. 20 ) has moved robotic syringe gripper  31  slightly to the left to disengage fixed syringe gripper jaw  50   a  and fixed plunger gripper jaw  55   a  from syringe  5  and plunger  6 , respectively. Actuator  73  has been activated to bump on the top of plunger gripper  55 . The bumping creates shock waves that travel through plunger gripper  55  and syringe gripper  50 . The shock waves help ensure that syringe  5  and plunger  6  are totally released from plunger gripper  55  and syringe gripper  50 . Plunger present sensor  64  verifies that syringe and plunger have been totally released.  
         [0055]     In  FIG. 42  linear actuator  60  has raised platform  61 . Robotic syringe gripper  31  can now be positioned above another dispenser to remove liquid in a fashion similar to that described above.  
         [0056]     For example, in one preferred embodiment robotic syringe gripper  31  is positioned over dispenser  3   a   1  to remove liquid contained in dispenser  3   a   1 . The solution in dispenser  3   a   1  is different than the solution in dispenser  3   b   7 . After removing the solution from dispenser  3   a   1 , robotic syringe gripper  31  deposits the solution into wells  33   a   1 - 33   a   8  ( FIGS. 33-35 ) in a fashion similar to that described above. The solutions from dispensers  3   a   1  and  3   b   7  are consequently mixed inside the wells of micro-well plate  33   a  to form a chemical solution suitable for use in proteomic crystal trials in protein crystallography.  
       Locating Indentations  
       [0057]     In the third preferred embodiment, dispensers  3   a   1 - 3   e   10  include locating indentations  100  and  101  ( FIG. 43 ).  FIG. 43  shows a top view of dispenser  3   b   7  with locating indentations  101  and  100 .  FIG. 2A  also shows a perspective view of locating indentations  100  and  101 . Platform  30  includes locating pins  102  arranged as shown in  FIG. 44 . Dispensers  3   a   1 - 3   e   10  are arranged on platform  30  so that locating indentations  100  and  101  are aligned with locating pins  102 . By utilization of locating pins  102  and locating indentions  100  and  101 , dispensers  3   a   1 - 3   e   10  can be precisely positioned on platform  30  and undesirable movement of the dispensers can be virtually eliminated.  
         [0058]     Although the above-preferred embodiments have been described with specificity, persons skilled in this art will recognize that many changes to the specific embodiments disclosed above could be made without departing from the spirit of the invention. For example, bottle  1  ( FIG. 2B ) can be made out of other materials besides plastic. In one preferred embodiment, for example, bottle  1  is glass. Also, retaining clip  4  can be made out of variety of materials such as plastic or metal. Also, tilted bottom component  9  can be molded such that its vertical sides extend up inside dispenser  3  to a height that is higher than the dispensing level. This would help minimize that possibility of liquid leaking through the connection of bottom component  9 . Also, although it was described in detail how robotic syringe grabber  31  ( FIG. 17 ) is utilized to remove syringes from dispensers  3   a   1 - 3   e   10 , it should be recognized that robotic syringe grabber  31  can also be utilized to similarly remove syringes from a variety of dispenser types for the purpose of dispensing liquid. For example, robotic syringe grabber  31  can be used to remove a syringe from a simple bottle having a syringe positioned at its opening. Therefore, the attached claims and their legal equivalents should determine the scope of the invention.