Nanoliter pipetting device

• US 10,137,444 B2
• Filed: 05/09/2017
• Issued: 11/27/2018
• Est. Priority Date: 05/11/2016
• Status: Active Grant

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Beroz, Justin, Rothman, Jacob, Samsel, Adrian, Hart, Anastasios John
• Primary Examiner(s): Shah, Manish S
• Assistant Examiner(s): Nath, Suman K
• Application Number:
  US15/590,131
• Publication Number:
  US 20170326542A1
• Time in Patent Office: 567 Days
• Field of Search: 7386411, 7386413, 7386416, 422501, 422502, 422504, 422505, 422516, 422922, 422923, 436180
• CPC Class Codes: B01L 2200/023 adapted for different sizes of tubes, tips or container
• CPC Class Codes: B01L 2300/14 Means for pressure control
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 3/02 Burettes; Pipettes
• CPC Class Codes: B01L 3/021 Pipettes, i.e. with only one conduit for withdrawing and redistributing liquids
• CPC Class Codes: B01L 3/0217 of the plunger pump type medical syringes A61M
• CPC Class Codes: B01L 3/0241 Drop counters; Drop formers making arrays for combinatorial libraries B01J19/0046; automation of dispensing for analysis G01N35/10
• CPC Class Codes: B01L 3/0275 Interchangeable or disposable dispensing tips

Abstract

Nanoliter pipette assembly. The assembly includes a housing containing a working fluid in a working fluid chamber therein and includes a moveable piston within the housing, the piston moveable by a linear actuation mechanism for contact with the working fluid. A tip portion is provided that includes a diaphragm deformable to engage an inner portion of the tip. It is preferred that the diaphragm have a projecting three-dimensional structure for direct contact with a liquid.

Claims

1. A nanoliter pipette assembly, comprising:

a housing having a working fluid chamber, the working fluid chamber being configured to contain a working fluid therein;

a tip portion having a diaphragm disposed therein, an adjustable interior cavity defined by a volume disposed between the diaphragm and a distal interior wall of the tip portion, and an orifice for aspirating and dispensing fluid, the orifice being located at and distal of the distal interior wall; and

a piston moveable within the housing to apply a force to a working fluid contained in the working fluid chamber to selectively move the diaphragm towards and away from the distal interior wall of the tip portion,

wherein the assembly is configured to operate to cause the diaphragm to contact fluid disposed at a location outside of the tip portion and subsequently draw the diaphragm away from the distal interior wall of the tip portion to draw at least a portion of the contacted fluid through the orifice and into the adjustable interior cavity, and

wherein the assembly is further configured to operate to advance the diaphragm towards the distal interior wall of the tip portion to displace at least a portion of the fluid previously passed into the adjustable interior cavity to a dispensing location outside of the tip portion, the at least a portion of the fluid previously passed into the adjustable interior cavity that is advanced to the dispensing location being as small as one nanoliter.

2. The nanoliter pipette assembly of claim 1, wherein the diaphragm further comprises a projection configured to pass through the orifice to contact fluid disposed at a location outside of the tip portion to draw at least a portion of the contacted fluid through the orifice and into the adjustable interior cavity.

3. The nanoliter pipette assembly of claim 2, wherein the diaphragm, the projection, and the distal interior wall of the tip portion are configured to be wetted by the fluid drawn through the orifice and into the adjustable interior cavity.

4. The nanoliter pipette assembly of claim 1, wherein prior to drawing the diaphragm away from the distal interior wall of the tip portion to draw fluid disposed at a location outside of the tip portion through the orifice and into the adjustable interior cavity, the assembly is configured to operate to advance the diaphragm towards the distal interior wall of the tip portion to displace an initial volume of fluid disposed in the adjustable interior cavity through the orifice and to a location outside of the tip portion, the location to which the initial volume of fluid is displaced being the location from which fluid is subsequently drawn into the orifice by drawing the diaphragm away from the distal interior wall of the tip portion.

5. The nanoliter pipette assembly of claim 1, wherein the linear actuation mechanism includes a series of cams configured to provide repeatability and adjustability of the amount of fluid drawn through the orifice and into the adjustable interior cavity.

6. The nanoliter pipette assembly of claim 1, further comprising a linear actuation mechanism configured to move the piston within the housing, the linear actuation mechanism further comprising a stop to set the amount of fluid drawn through the orifice and into the adjustable interior cavity, and the linear actuation mechanism being further configured to:

depress the piston to a bottom of its stroke to bringing a projection on the diaphragm into contact with the fluid disposed at a location outside of the tip portion;

retract the piston to aspirate the fluid through the orifice and into the adjustable interior cavity; and

deflect the diaphragm towards a maximum position thereof to displace at least a portion of the fluid previously passed into the adjustable interior cavity to the dispensing location.

7. The nanoliter pipette assembly of claim 5, further including a thumb push button coupled to the series of cams providing an eight step operation of the pipette assembly to aspirate and then dispense the fluid, the thumb push button having an adjustable-range click-pen-type mechanism.

8. A nanoliter pipette assembly, comprising:

a housing having a working fluid chamber, the working fluid chamber being configured to contain a working fluid therein;

a tip portion having a diaphragm disposed therein, an adjustable interior cavity defined by a volume disposed between the diaphragm and a distal interior wall of the tip portion, and an orifice located at and distal of the distal interior wall; and

a piston moveable within the housing to apply a force to a working fluid contained in the working fluid chamber to selectively move the diaphragm towards and away from the distal interior wall of the tip portion,

wherein the diaphragm is configured to move from a first rest position to a second displacement position as the piston is advanced towards the tip portion such that fluid disposed in the adjustable interior cavity is displaced out of the adjustable interior cavity to a location outside of the tip portion via the orifice,

wherein the diaphragm is further configured to move from the second displacement position to a third position as the piston is retracted away from the tip portion to draw fluid disposed at a location outside of the tip portion through the orifice and into the adjustable interior cavity, the third position being disposed between the first rest position and the second displacement position and being a designated position such that the diaphragm is configured to stop and rest at the third position without any external forces being supplied by a user of the nanoliter pipette assembly, and

wherein the diaphragm is further configured to move from the third position towards the second displacement position as the piston is advanced towards the tip portion to displace at least a portion of the fluid previously passed into the adjustable interior cavity to a dispensing location outside of the tip portion, the at least a portion of the fluid previously passed into the adjustable interior cavity that is advanced to the dispensing location being as small as one nanoliter.

9. The nanoliter pipette assembly of claim 8, wherein the diaphragm further comprises a projection configured to pass through the orifice to contact fluid disposed at a location outside of the tip portion to draw the fluid through the orifice and into the adjustable interior cavity.

10. The nanoliter pipette assembly of claim 9, wherein the diaphragm, the projection, and the distal interior wall of the tip portion are configured to be wetted by the fluid drawn through the orifice and into the adjustable interior cavity.

11. The nanoliter pipette assembly of claim 8, wherein the third position is a metered position.

12. The nanoliter pipette assembly of claim 11, wherein the metered position is adjustable such that the amount of fluid drawn through the orifice and into the adjustable interior cavity when the diaphragm moves from the second displacement position to the third position can be adjusted by changing a location of the metered position.

13. The nanoliter pipette assembly of claim 12, further comprising a linear actuation mechanism configured to move the piston, the linear actuation mechanism including a series of cams configured to adjust the metered position of the diaphragm.

14. The nanoliter pipette assembly of claim 13, further comprising a thumb push button coupled to the series of cams to provide for movement of the diaphragm between the second displacement position and the metered position to draw the second volume amount into the adjustable interior cavity, and to provide for movement of the diaphragm from the metered position and towards the second displacement position to displace at least a portion of the second volume amount of the working fluid out of the orifice, the thumb push button having an adjustable-range click-pen-type mechanism.

15. The nanoliter pipette assembly of claim 8, further comprising a linear actuation mechanism having a stop configured to set the amount of fluid drawn through the orifice and into the adjustable interior cavity when the diaphragm moves from the second displacement position to the third position by setting a location of the third position of the diaphragm, and the linear actuation mechanism is configured to:

depress the piston to a bottom of its stroke to bring a projection on the diaphragm into contact with the fluid disposed at a location outside of the tip portion, prior to drawing the fluid into the adjustable interior cavity;

retract the piston to draw the fluid disposed at a location outside of the tip portion into the adjustable interior cavity; and

deflect the diaphragm towards the second displacement position to displace at least a portion of the fluid previously passed into the adjustable interior cavity, out of the orifice, and to the dispensing location.

16. A pipette assembly, comprising:

a housing having a working fluid chamber, the working fluid chamber being configured to contain a working fluid therein;

a tip portion having a diaphragm disposed therein, an adjustable interior cavity defined by a volume disposed between the diaphragm and a distal interior wall of the tip portion, and an orifice located at and distal of the distal interior wall; and

a piston moveable within the housing to apply a force to a working fluid contained in the working fluid chamber to selectively move the diaphragm towards and away from the distal interior wall of the tip portion,

wherein the diaphragm is configured to move from a first rest position to a second displacement position as the piston is advanced towards the tip portion such that fluid disposed in the adjustable interior cavity is displaced out of the adjustable interior cavity to a location outside of the tip portion via the orifice, and

wherein the second displacement position is such that the diaphragm conforms to the distal interior wall of the tip portion, resulting in a volume of the adjustable interior cavity being zero.

17. The pipette assembly of claim 16, wherein the diaphragm is further configured to move from the second displacement position to a third position as the piston is retracted away from the tip portion to draw fluid disposed at a location outside of the tip portion through the orifice and into the adjustable interior cavity, the portion of the volume of the fluid being defined as a displacement volume of the fluid, and the third position being disposed between the first rest position and the second displacement position, and

wherein the diaphragm is further configured to move from the third position towards the second displacement position as the piston is advanced towards the tip portion to displace at least a portion of the displacement volume out of the orifice.

18. The pipette assembly of claim 17, wherein the diaphragm moves to the second placement position to displace the at least a portion of the displacement volume out of the orifice, thus displacing the displacement volume.

19. The pipette assembly of claim 17, wherein the diaphragm further comprises a projection configured to pass through the orifice to contact fluid disposed at a location outside of the tip portion to draw the fluid through the orifice and into the adjustable interior cavity.

20. The pipette assembly of claim 19, wherein the diaphragm, the projection, and the distal interior wall of the tip portion are configured to be wetted by the displacement volume of the fluid.

21. The pipette assembly of claim 17, comprising a linear actuation mechanism configured to move the piston, the linear actuation mechanism including a series of cams configured to adjust the third position of the diaphragm.