Apparatus and method for mixing a film of fluid

• US 6,186,659 B1
• Filed: 08/21/1998
• Issued: 02/13/2001
• Est. Priority Date: 08/21/1998
• Status: Expired due to Fees

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Schembri, Carol T.
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): Chorbaji, Monzer R.
• Application Number:
  US09/137,963
• Time in Patent Office: 907 Days
• Field of Search: 422/102, 422/104, 422/944, 422/292, 422/307, 436/174, 436/180, 436/181, 122/292, 122/307, 366/182.1, 366/182.2, 366/262, 366/144, 417/207, 417/208, 417/52
• US Class Current: 366/262
• CPC Class Codes: B01F 2215/0431 Numerical size values, e.g. diameter of a hole or conduit, area, volume, length, width, or ratios thereof
• CPC Class Codes: B01F 2215/0472 Numerical temperature values
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01F 33/40 Mixers using gas or liquid agitation, e.g. with air supply tubes
• 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 2219/00479 Means for mixing reactants or products in the reaction vessels
• CPC Class Codes: B01J 2219/00495 Means for heating or cooling the reaction vessels
• CPC Class Codes: B01J 2219/00536 in the shape of disks
• CPC Class Codes: B01J 2219/0059 Sequential 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 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00653 the compounds being bound to electrodes embedded in or on the solid supports
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B01J 2219/1941 circular or disk-shaped
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0803 : Disc shape
• CPC Class Codes: B01L 2300/0887 : Laminated structure
• CPC Class Codes: B01L 2300/1827 : using resistive heater
• CPC Class Codes: B01L 2400/0406 : capillary forces
• CPC Class Codes: B01L 2400/0409 : centrifugal forces
• CPC Class Codes: B01L 2400/0442 : thermal energy, e.g. vaporisation, bubble jet
• CPC Class Codes: B01L 2400/0448 : Marangoni flow; Thermocapillary effect
• CPC Class Codes: B01L 2400/0487 : fluid pressure, pneumatics
• CPC Class Codes: B01L 3/502707 : characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• CPC Class Codes: B01L 3/50273 : characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 40/10 : Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: C40B 40/14 : Libraries containing macromolecular compounds and not covered by groups C40B40/06 - C40B40/12
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: Y10S 366/03 : Micromixers: variable geometry from the pathway influences mixing/agitation of non-laminar fluid flow
• CPC Class Codes: Y10T 436/25 : including sample preparation

Abstract

A method and apparatus is provided for mixing a film of fluid, particularly a film of chemical, biochemical, or biological fluids undergoing a reaction. The apparatus comprises a means for nucleating a bubble using a discrete heat source, such as a resistor, and moving the bubble in the fluid by creating a temperature gradient, thereby mixing the fluid.

Claims

1. An apparatus for mixing a film of fluid, comprising:

a first substrate and a substantially parallel second substrate having inner surfaces that define a closed chamber therebetween, said chamber adapted to retain a film of fluid so that the fluid is in contact with both inner surfaces; and

means for nucleating bubbles in the fluid comprising discrete heat sources for creating individual bubbles at selected locations within the apparatus, whereby, as each bubble is nucleated and dispelled, the fluid is displaced resulting in mixing.

2. The apparatus of claim 1, further comprising means for moving a bubble in the fluid.

3. The apparatus of claim 1 wherein said means for nucleating bubbles also comprises means for moving a bubble in the fluid.

4. The apparatus of claim 1 wherein the closed chamber has a thickness of less than about 1 millimeter.

5. The apparatus of claim 4 wherein the closed chamber has a thickness of less than about 100 microns.

6. The apparatus of claim 4 wherein said means for nucleating bubbles also comprises means for moving a bubble in the fluid.

7. The apparatus of claim 1 wherein one of said inner surfaces is functionalized with reactive moieties.

8. The apparatus of claim 7 wherein the reactive moieties comprise reactive sites of monomeric species present at the terminus of a surface-bound polymer.

9. The apparatus of claim 8 wherein the surface-bound polymer comprises a polynucleotide.

10. The apparatus of claim 8 wherein the surface-bound polymer comprises a polyribonucleotide.

11. The apparatus of claim 8 wherein the surface-bound polymer comprises a polypeptide.

12. The apparatus of claim 7 wherein said means for nucleating bubbles also comprises means for moving a bubble in the fluid.

13. The apparatus of claim 7 wherein the reactive moieties comprise polynucleotide, polyribonucleotide, or polypeptide.

14. The apparatus of claim 7 wherein the reactive moieties comprise monomeric species covalently bound to said inner surface, each of the monomeric species having at least one reactive site.

15. The apparatus of claim 14 wherein the monomeric species are amino acids.

16. The apparatus of claim 14 wherein the monomeric species are nucleotides.

17. The apparatus of claim 1 wherein each of said inner surfaces is functionalized with reactive moieties.

18. The apparatus of claim 1, wherein the means for nucleating bubbles comprises a discrete heat source adjacent one of said inner surfaces.

19. The apparatus of claim 18 wherein the chamber has a volume of less than 300 μ

l.

20. The apparatus of claim 1 wherein the means for nucleating bubbles comprises discrete heat sources adjacent said inner surfaces.

21. The apparatus of claim 20 wherein the discrete heat sources are resistors.

22. The apparatus of claim 21 wherein the discrete heat sources comprise resistors arranged in a predetermined pattern.

23. The apparatus of claim 20 wherein the means for nucleating bubbles comprises a plurality of discrete heat sources adjacent said inner surface.

24. The apparatus of claim 1 wherein the means for nucleating bubbles comprises a discrete heat source adjacent each said inner surface.

25. The apparatus of claim 1, further including a seal between the inner surface of the first substrate and the inner surface of the second substrate.

26. The apparatus of claim 25 wherein the seal is flexible.

27. The apparatus of claim 1, further including a means for introducing fluid into the closed chamber to provide a film of fluid therein.

28. The apparatus of claim 1 wherein each of the first substrate and the second substrate individually comprises a material selected from the group consisting of glass, silicon, fused silica, plastic, ceramic, and metal.

29. The apparatus of claim 1 wherein the chamber has a volume of less than 300 μ

l.

30. A method for mixing a film of fluid, comprising:

providing a first substrate and a substantially parallel second substrate having inner surfaces that define a closed chamber therebetween, said chamber adapted to retain a quantity of fluid so that the fluid is in contact with both inner surfaces;

introducing a fluid containing a plurality of components into the closed chamber so as to provide a film of fluid therein; and

nucleating a bubble within the film of fluid, whereby, as the bubble is nucleated and dispelled, the fluid is displaced resulting in mixing.

31. The method of claim 30 wherein the dispelling comprises moving the bubble.

32. The method of claim 30 wherein the dispelling comprises collapsing the bubble.

33. The method of claim 30 wherein the means for nucleating a bubble comprises heating using a plurality of discrete heat sources adjacent one of said inner surfaces.

34. The method of claim 33 wherein the discrete heat sources comprise resistors arranged in a predetermined pattern.

35. The method of claim 30 wherein the means for nucleating a bubble comprises heating using a plurality of discrete heat sources adjacent both of said inner surfaces.

36. The method of claim 30 wherein one of said inner surfaces is functionalized with reactive moieties.

37. The method of claim 36 wherein the reactive moieties comprise reactive sites of monomeric species present at the terminus of a surface-bound polymer.

38. The method of claim 37 wherein the surface-bound polymer comprises a polynucleotide.

39. The method of claim 37 wherein the surface-bound polymer comprises a polyribonucleotide.

40. The method of claim 37 wherein the surface-bound polymer comprises a polypeptide.

41. The method of claim 36 wherein the reactive moieties comprise monomeric species covalently bound to the inner surface, each of the monomeric species having at least one reactive site.

42. The method of claim 41 wherein the monomeric species are nucleotides.

43. The method of claim 41 wherein the monomeric species are amino acids.

44. The method of claim 30 wherein each of said inner surfaces is functionalized with reactive moieties.

45. The method of claim 30, further including introducing fluid into the closed chamber to provide a film of fluid therein.

46. The method of claim 30, further including defining the thickness of the film by enclosing the fluid between said surfaces and ensuring that the film is retained in the closed chamber.