Acoustically mediated fluid transfer methods and uses thereof

• US 20030203386A1
• Filed: 03/28/2003
• Published: 10/30/2003
• Est. Priority Date: 12/12/2000
• Status: Abandoned Application

• Current Assignee: Lawrence Lee Jr, Mansour N. Nicolas, Michael J. Forbush, Roger O. Williams, Tarlochan Singh
• Original Assignee: Lawrence Lee Jr, Mansour N. Nicolas, Michael J. Forbush, Roger O. Williams, Tarlochan Singh
• Inventors: Forbush, Michael J., Williams, Roger O., Singh, Tarlochan, Lee, Lawrence Jr., Mansour, N. Nicolas
• Application Number:
  US10/402,707
• Publication Number:
  US 20030203386A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00362 Acoustic nozzles
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00641 the porous medium being continuous, e.g. porous oxide substrates
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 2400/0433 vibrational forces
• CPC Class Codes: B01L 2400/0436 acoustic forces, e.g. surface acoustic waves [SAW]
• CPC Class Codes: B01L 3/0268 using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
• CPC Class Codes: B05B 17/0615 spray being produced at the free surface of the liquid or other fluent material in a container and subjected to the vibrations
• CPC Class Codes: C40B 30/04 by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding
• CPC Class Codes: C40B 40/02 Libraries contained in or displayed by microorganisms, e.g. bacteria or animal cells; Libraries contained in or displayed by vectors, e.g. plasmids; Libraries containing only microorganisms or vectors
• CPC Class Codes: C40B 40/04 Libraries containing only organic compounds
• CPC Class Codes: C40B 40/08 : Libraries containing RNA or DNA which encodes proteins, e.g. gene libraries
• CPC Class Codes: C40B 40/10 : Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: C40B 50/00 : Methods of creating libraries, e.g. combinatorial synthesis
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: F04F 7/00 : Pumps displacing fluids by using inertia thereof, e.g. by generating vibrations therein
• CPC Class Codes: G01N 21/11 : Filling or emptying of cuvettes
• CPC Class Codes: Y10T 137/206 : Flow affected by fluid contact, energy field or coanda effect [e.g., pure fluid device or system]
• CPC Class Codes: Y10T 137/2196 : Acoustical or thermal energy
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

Acoustic waves are used to transfer small amounts of fluid in a non-contact manner. Acoustic waves are propagated through a pool of a source fluid in such a manner that causes the ejection of a single micro-droplet from the surface of the pool. The droplet is ejected towards a target with sufficient force to provide for contact of the droplet with the target. Because the fluid is not contacted by any fluid transfer device such as a pipette, the opportunities for contamination are minimized. Methods may be employed to transfer fluids from an array of source sites to an array of target sites, thereby enabling the precise automation of a wide variety of procedures including screening and synthesis procedures commonly used in biotechnology.

Claims

1. A non-contact method for transferring small amounts of source fluid, said method comprising propagating an acoustic wave from an acoustic liquid deposition emitter through a source fluid containment structure into a source fluid, wherein:

a) said acoustic liquid deposition emitter is in contact with said source fluid containment structure through a coupling medium which is interposed between said acoustic liquid deposition emitter and a first surface of said source fluid containment structure,

b) said source fluid is on a second surface of said source fluid containment structure that is opposite said acoustic liquid deposition emitter, and

c) said acoustic wave causes controlled ejection of at least one droplet of said source fluid from said pool.

2. A method according to claim 1, wherein said at least one droplet contacts a target after being ejected from the surface of said source fluid.

3. A method according to claim 1, wherein said acoustic liquid deposition emitter comprises a piezoelectric transducer for generation of said acoustic wave.

4. A method according to claim 3, wherein said piezoelectric transducer is mechanically coupled to an acoustic wave channel structure, wherein said acoustic wave channel structure has an acoustic impedance that is greater than the acoustic impedance of said source fluid.

5. A method according to claim 3, wherein said acoustic liquid deposition emitter further comprises a lens for focusing said acoustic wave.

6. A method according to claim 5, wherein said lens is spherical.

7. A method according to claim 5, wherein said lens has an f value in the range of about 1 to about 4.

8. A method according to claim 1, wherein said at least one droplet has a defined diameter.

9. A method according to claim 8, wherein said defined diameter is in the range of about 1 micrometer to about 1000 micrometers.

10. A method according to claim 8, wherein said defined size is controlled by varying one or more of frequency, voltage, and duration of an energy source used to excite a piezoelectric transducer and thereby propagate said acoustic wave.

11. A method according to claim 1, wherein said source fluid is contained within a well having a bottom, sides and an open top for the ejection of said droplet there through.

12. A method according to claim 1, wherein said source fluid containment structure comprises one or more regions of hydrophilicity for containing said source fluid.

13. A method according to claim 2, wherein said source fluid containment structure comprises an array of source fluids, and wherein said target comprises an array of target regions for receiving said droplet.

14. A method according to claim 13, wherein each source fluid in the array of source fluids comprises a different source fluid.

15. A method according to claim 13, wherein said array of source fluids is contained in an array of source wells, wherein each of said wells comprises a bottom, sides and an open top for the ejection of said droplet there through.

16. A method according to claim 13, wherein said target region is positioned opposite a selected source fluid, such that liquid ejected from the selected source fluid contacts said target region.

17. A method according to claim 15, wherein said method further comprises positioning of said acoustic liquid deposition emitter relative to said array of source wells to provide for user-defined association of said acoustic liquid deposition emitter with a selected source fluid for ejection of at least one droplet therefrom.

18. A method according to claim 17, wherein said positioning is accomplished by computer-controlled translation of said liquid deposition emitter with respect to said array of source wells.

19. A method according to claim 17, wherein said positioning is accomplished by computer-controlled translation of said array of source wells with respect to said liquid deposition emitter.

20. A method according to claim 1, wherein said source fluid comprises one or more source materials.

21. A method according to claim 20, wherein said source materials comprises one or more biological or chemical compounds.

22. A method according to claim 21, wherein said source material bears a detectable label.

23. A method according to claim 22, wherein said detectable label is fluorescent or radioactive.

24. A method according to claim 21, wherein said biological source material comprises a nucleic acid, a polypeptide, a eukaryotic cell, a prokaryotic cell, or a combination thereof.

25. A method according to claim 24, wherein said nucleic acid is DNA or RNA.

26. A method according to claim 24, wherein said polypeptide is an antibody, an enzyme, or an immunogen.

27. A method according to claim 21, wherein said source material is a mono- or oligonucleotide, or combination thereof.

28. A method according to claim 27, wherein said oligonucleotide comprises 2 to 10 nucleotide bases.

29. A method according to claim 27, wherein said oligonucleotide comprises 5 nucleotide bases.

30. A method according to claim 27, wherein said mono or oligonucleotides are combined on a target under conditions to form a single product oligonucleotide.

31. A method according to claim 30, wherein in said target is functional for binding one or more source materials.

32. A method according to claim 31, wherein said target bears one or more target materials.

33. A method according to claim 32, wherein said target material comprise biological or chemical compounds.

34. A method according to claim 33, wherein said biological target material comprises a nucleic acid, a polypeptide, or a combination thereof.

35. A method according to claim 34, wherein said nucleic acid is DNA or RNA.

36. A method according to claim 32, wherein said target material is a mono- or oligonucleotide or a combination thereof.

37. A method according to claim 36, wherein said oligonucleotide comprises 2 or more nucleotide bases.

38. A method according to claim 30, wherein said mono- or oligonucleotide are systematically combined on said target under conditions to form a single product oligonucleotide.

39. A method according to claim 2, wherein said target comprises a biological or chemical target material.

40. A method according to claim 39, wherein said biological target material is a polypeptide, an antibody, an enzyme, or an immunogen.

41. A method according to claim 1, further comprising detecting the volume or level of source fluid present in said fluid containment structure.

42. A method according to claim 41, wherein said detecting is performed by directing an acoustic wave at said source fluid, receiving a reflection of said acoustic wave, and determining the level of said source fluid based on the characteristics of said reflected acoustic wave.

43. A method according to claim 41, wherein said volume level is performed by an acoustical detector coupled to a computer, and wherein said computer computes a change in volume or level based on a signal received from the detector before said ejecting of said droplet, and after said ejecting of said droplet.

44. A non-contact method for transferring small amounts of a source fluid to a separate target structure, said method comprising activating a piezoelectric transducer thereby propagating an acoustic wave through a coupling medium which is interposed between said piezoelectric transducer and a first surface of a source fluid containment structure, wherein

a) said source fluid is contained on a second surface of said source fluid containment structure that is opposite said piezoelectric transducer,

b) said target is positioned to receive a droplet of fluid ejected from said source fluid as a result of propagation of said acoustic wave through said source fluid.

45. A method for transferring small amounts of a source fluid from a pool selected from one of a plurality of pools of source fluid located on a first surface of a source fluid containment structure, to a separate target structure without physically contacting said source fluid, said method comprising propagating an acoustic wave through said source fluid such that a single droplet of fluid is ejected from the surface of said pool with sufficient energy to bring said droplet into contact with said target, wherein

a) said acoustic wave is propagated from a piezoelectric transducer,

b) said piezoelectric transducer is in contact with said source fluid containment structure via a coupling medium interposed between said piezoelectric transducer and a second surface of said source fluid containment structure,

c) said second surface of said source fluid containment structure is opposite said pool, and

d) said target is opposite said surface of said pool.

46. An apparatus for performing non-contact transfer of small amounts of source fluid, said apparatus comprising an acoustic liquid deposition emitter and a stage wherein:

a) said stage supports a source fluid containment structure,

b) said source fluid containment structure being supported such that said acoustic liquid deposition emitter is in operative contact with said source fluid containment structure when a coupling medium is interposed there between.

47. The apparatus of claim 46, wherein said apparatus further comprises an acoustic wave channel structure that is mechanically coupled to the acoustic liquid deposition emitter.

48. The apparatus of claim 46, wherein acoustic liquid deposition emitter further comprises a lens for focusing an acoustic wave.

49. The apparatus of claim 48, wherein said lens is spherical.

50. The apparatus of claim 48, wherein said lens has an f value in the range of about 1 to about 4.

51. The apparatus of claim 46, wherein said acoustic liquid deposition emitter comprises a piezoelectric transducer.

52. The apparatus of claim 46, further comprising controls for varying one or more of frequency, voltage, and duration of an energy source used to excite said piezoelectric transducer and thereby propagate an acoustic wave therefrom.

53. The apparatus of claim 46, further comprising a fluid level detector for detecting a level or volume of fluid in a source fluid containment structure.

54. The apparatus of claim 46, wherein the stage is movable relative to the acoustic liquid deposition emitter.

55. The apparatus of claim 46, wherein the stage is movable relative to a target.

56. An apparatus for performing non-contact transfer of small amounts of source fluid to a target, said apparatus comprising an acoustic liquid deposition emitter and a stage wherein:

a) said stage is configured to support a source fluid containment structure whereby the acoustic liquid deposition emitter is coupled to a first surface of the source fluid containment structure by a coupling medium interposed between said acoustic liquid deposition emitter and said first surface of the source fluid containment structure, such that

b) an acoustic wave generated by said acoustic liquid deposition emitter and transmitted through said coupling medium to said first surface of the source fluid containment structure and thereafter propagates through said source fluid containment structure into a pool of source fluid on a second surface of said source fluid containment structure opposite said acoustic liquid deposition emitter, causing controlled ejection of at least one droplet of said source fluid from said pool.

57. A system for performing non-contact transfer of small amounts of source fluid, comprising:

a source fluid containment structure;

a movable stage, configured to support the source fluid containment structure;

an acoustic liquid deposition emitter in operative contact with the source fluid containment structure;

a coupling medium interposed between the deposition emitter and the source fluid containment structure;

a fluid level detector for detecting a level or volume of fluid in a source fluid containment structure;

a lens in operative association with the acoustic liquid deposition emitter for focusing an acoustic wave; and

a computer in operable communication with the acoustic liquid deposition emitter for varying one or more of frequency of the acoustic wave;

voltage of an energy source used to excite the acoustic liquid deposition emitter;

duration of an energy source used to excite the acoustic liquid deposition emitter, or location of the stage relative to the acoustic deposition emitter; and

wherein the computer comprises a computer implemented algorithm for adjusting one or more of;

frequency of the acoustic wave;

voltage of an energy source used to excite the acoustic liquid deposition emitter;

duration of an energy source used to excite the acoustic liquid deposition emitter, or location of the stage relative to the acoustic deposition emitter in response to a change in fluid level or volume detected by the fluid level detector.