HIGH RESOLUTION PIPETTE

• US 20130283884A1
• Filed: 04/30/2013
• Published: 10/31/2013
• Est. Priority Date: 04/30/2012
• Status: Active Grant

• Current Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Original Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Inventors: Hart, Anastasios John, Beroz, Justin Douglas
• Granted Patent: US 9,358,538 B2
• Time in Patent Office: Days
• US Class Current: 73/1.74
• CPC Class Codes: B01L 2200/023 adapted for different sizes of tubes, tips or container
• CPC Class Codes: B01L 2200/141 Preventing contamination, tampering
• CPC Class Codes: B01L 2200/146 Employing pressure sensors
• CPC Class Codes: B01L 2200/148 Specific details about calibrations
• CPC Class Codes: B01L 2400/0478 pistons
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 3/0217 of the plunger pump type medical syringes A61M
• CPC Class Codes: B01L 3/0275 Interchangeable or disposable dispensing tips
• CPC Class Codes: B01L 3/0293 for liquids

Abstract

A pipette includes a movable piston and a diaphragm that at least partly defines a fluid chamber enclosing a volume of working fluid. The piston displaces a volumetric amount of the working fluid in the chamber when moved. In response, the diaphragm displaces a smaller volumetric amount of fluid outside the chamber. A deamplification ratio is defined by the ratio of the volume displaced by the diaphragm to the volume displaced by the piston. The deamplification ratio is adjustable by adjusting or changing the diaphragm and/or by adjusting the size of the fluid chamber. The deamplifying pipette enables measuring and dispensing of very small volumes of liquid and is easily adapted to commercially available pipette components. Pipette components such as a pipette tip or adaptor may include a diaphragm to enable deamplification of the nominal volume capacity of a given pipette device.

Claims

1. A pipette device, comprising:

a fluid chamber having an enclosed volume of working fluid;

a piston that partially defines the fluid chamber, the piston being movable to displace the working fluid within the fluid chamber; and

a diaphragm that partially defines the fluid chamber, the diaphragm having a chamber side in contact with the working fluid and an opposite side that displaces a measurement volume of fluid outside the fluid chamber when the piston moves to displace a volumetric amount of working fluid, wherein the measurement volume is less than the volumetric amount of working fluid displaced by the piston.

2. A pipette device as defined in claim 1, wherein the working fluid is a compressible fluid.

3. A pipette device as defined in claim 1, wherein the working fluid is an incompressible fluid.

4. A pipette device as defined in claim 1, wherein the diaphragm undergoes elastic deformation when the piston moves against the enclosed volume of working fluid.

5. A pipette device as defined in claim 1, further comprising a secondary diaphragm that defines a portion of the fluid chamber and that undergoes elastic deformation when the piston moves against the enclosed volume of working fluid.

6. A pipette device as defined in claim 1, further comprising a housing that defines a portion of the fluid chamber, wherein at least a portion of the housing undergoes elastic deformation when the piston moves against the enclosed volume of working fluid.

7. A pipette device as defined in claim 1, further comprising a resolution adjustment mechanism.

8. A pipette device as defined in claim 7, wherein the resolution adjustment mechanism includes a portion that partly defines the fluid chamber, said portion being movable to change the volume of the fluid chamber independently from the piston.

9. A pipette device as defined in claim 7, wherein the resolution adjustment mechanism includes an interchangeable diaphragm.

10. A pipette device as defined in claim 9, wherein said diaphragm that partially defines the fluid chamber is a primary diaphragm, the pipette device further comprises a secondary diaphragm that partially defines the fluid chamber, and the primary diaphragm is the interchangeable diaphragm.

11. A pipette device as defined in claim 9, wherein said diaphragm that partially defines the fluid chamber is a primary diaphragm and the interchangeable diaphragm is a secondary diaphragm.

12. A pipette device as defined in claim 7, wherein the resolution adjustment mechanism includes a plurality of interchangeable diaphragms.

13. A pipette device as defined in claim 7, wherein the resolution adjustment mechanism includes a mechanism that changes the amount of surface area of the diaphragm, and/or of a secondary diaphragm, that the working fluid acts upon, thereby changing the effective stiffness of the diaphragm(s).

14. A pipette device as defined in claim 7, wherein the resolution adjustment mechanism includes a mechanism that stretches the diaphragm and/or a secondary diaphragm, thereby changing the effective stiffness of the diaphragm(s).

15. A pipette device as defined in claim 1, further comprising a valve operable to selectively allow fluid flow between the fluid chamber and a location outside of the fluid chamber.

16. A pipette device as defined in claim 15, wherein the location outside of the fluid chamber is at atmospheric pressure.

17. A pipette device as defined in claim 15, wherein the location outside of the fluid chamber is an adjustable pressure source.

18. A pipette device as defined in claim 1, further comprising a manual actuator that moves the piston.

19. A pipette device as defined in claim 1, further comprising an electrically operated actuator that moves the piston.

20. A pipette device as defined in claim 1, wherein the device is adapted for simultaneous attachment of a plurality of pipette tips such that the measurement volume is divided among the plurality of pipette tips.

21. A pipette device as defined in claim 20, comprising a plurality of diaphragms, wherein each of the plurality of diaphragms has a chamber side in contact with the working fluid and an opposite side configured to displace fluid along a corresponding one of the plurality of pipette tips.

22. A pipette device as defined in claim 1, wherein the measurement volume is selectable in a range that spans two or more orders of magnitude.

23. A pipette device as defined in claim 1, wherein the measurement volume is selectable in a range that includes measurement volumes of less than about 0.5 microliters.

24. A pipette device as defined in claim 1, wherein the measurement volume is selectable in a range from about 1 nanoliter to about 1 milliliter.

25. A pipette device as defined in claim 1, wherein the measurement volume is selectable in a range from about 10 nanoliters to about 10 microliters.

26. A pipette device as defined in claim 1, wherein a deamplification ratio is defined by the measurement volume divided by the volumetric amount of working fluid displaced by the piston, and said ratio is 0.25 or less.

27. A pipette device as defined in claim 26, wherein said ratio is 0.01 or less.

28. A pipette device as defined in claim 1, wherein the device has a range of selectable values for said volumetric amount of working fluid, and wherein the device is configured with a linear deamplification ratio over said range, the deamplification ratio being defined as the ratio of the measurement volume to the volumetric amount of working fluid displaced by the piston.

29. A pipette device as defined in claim 1, wherein the device has a range of selectable values for said volumetric amount of working fluid, and wherein the device is configured with a superlinear or sublinear deamplification ratio over said range, the deamplification ratio being defined as the ratio of the measurement volume to the volumetric amount of working fluid displaced by the piston.

30. A pipette component, comprising an elastic diaphragm supported by a housing, the diaphragm having a first side that defines a portion of a fluid chamber when the component is assembled as part of a pipette assembly, wherein the pipette component is adapted to deamplify fluid displacement within the fluid chamber at an opposite second side of the diaphragm at least partly via elastic deformation of the diaphragm.

31. A pipette component as defined in claim 30, wherein the component is a handheld pipette device that includes the fluid chamber and a piston that is movable to displace a working fluid within the fluid chamber, the pipette device being adapted for attachment to a pipette tip to form said pipette assembly.

32. A pipette component as defined in claim 30, wherein the component is a pipette tip adapted for removable attachment to a pipette device having a movable piston to form said pipette assembly.

33. A pipette component as defined in claim 30, wherein the component is a pipette adapter adapted for attachment between a pipette device and a pipette tip to form said pipette assembly so that portions of the pipette adapter and the pipette device together define the fluid chamber.

34. A pipette component as defined in claim 33, wherein the elastic diaphragm is interchangeable.

35. A pipette device comprising the pipette component of claim 33, the device being adapted for attachment of interchangeable pipette tips.

36. A pipette component as defined in claim 30, further comprising at least a portion of a resolution adjustment mechanism.

37. A method of calibrating a pipette device, the method comprising the steps of:

(a) attaching a calibration device including a pressure sensor to the pipette device to enclose a known volume of calibration fluid between the devices;

(b) moving a piston of the pipette device to displace a desired volumetric amount of calibration fluid;

(c) measuring the pressure change of the enclosed volume of calibration fluid resulting from step (b); and

(d) adjusting the pipette device based on the measurement in step (c).

38. The method of claim 37, wherein step (d) includes operating a resolution adjustment mechanism of the pipette device, and steps (b)-(d) are repeated until the measured pressure change corresponds to the desired volumetric amount of calibration fluid.