Method and apparatus for mixing a thin film of fluid

• US 5,910,288 A
• Filed: 07/10/1997
• Issued: 06/08/1999
• Est. Priority Date: 07/10/1997
• Status: Expired due to Fees

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Hewlett-Packard Company (HP Inc.)
• Inventors: Schembri, Carol T.
• Primary Examiner(s): MCKANE, ELIZABETH L
• Application Number:
  US08/889,763
• Time in Patent Office: 698 Days
• Field of Search: 422/102, 422/104, 422/174, 422/944, 436/180
• US Class Current: 422/551
• CPC Class Codes: B01F 31/31 using receptacles with deformable parts, e.g. membranes, to which a motion is imparted
• CPC Class Codes: B01F 33/30 Micromixers
• 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 19/1806 resulting in a turbulent flow of the reactants, such as in centrifugal-type reactors, or having a high Reynolds-number
• CPC Class Codes: B01J 19/1887 forming a thin film
• CPC Class Codes: B01J 2219/00051 Controlling the temperature
• CPC Class Codes: B01J 2219/00421 using centrifugation
• CPC Class Codes: B01J 2219/00536 in the shape of disks
• 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 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B01J 2219/00729 Peptide nucleic acids [PNA]
• CPC Class Codes: B01L 2300/0803 Disc shape
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0409 centrifugal forces
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• 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 60/14 : for creating libraries
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

The invention relates to a method and apparatus for mixing thin films of fluid, particularly thin films of chemical, biochemical, or biological fluids undergoing reactions. The invention employs a mixing mechanism which induces mixing within the fluid chamber by moving the inner face of at least one surface of the fluid chamber relative to the inner face of another surface of the fluid chamber, thus enhancing the sensitivity or specificity of the reaction, rate of reaction, extent of reaction, homogeneity, or percentage yield. The invention is particularly useful in enhancing the results of chemical and biological assays.

Claims

1. Apparatus for mixing a film of fluid, comprising:

a first substantially planar surface having an inner face;

a second substantially planar surface having an inner face, wherein the second surface is substantially parallel to and proximate to the first surface such that the inner face of the first surface is in opposing relationship to the inner face of the second surface and the two inner faces define a fluid chamber between the two surfaces;

optionally an opening in one of the surfaces for introducing fluid into the fluid chamber; and

means for rotating the first and second surfaces about an axis generally normal to the planes thereof at variable angular velocities in a range including higher velocities great enough to cause a fluid within the fluid chamber to move centrifugally away from the rotational axis, such that mixing of fluid is induced within the fluid chamber.

2. The apparatus of claim 1, wherein the fluid chamber has a thickness of less than about 1 millimeter.

3. The apparatus of claim 2, wherein the fluid chamber has a thickness of less than about 100 microns.

4. The apparatus of claim 1, wherein the fluid chamber has an active volume of less than about 150 microliters.

5. The apparatus of claim 1, wherein the surface area of each face of the first surface and second surface that comes in contact with fluid is less than about 20 square centimeters.

6. The apparatus of claim 1, wherein each of the first surface and the second surface are in the shape of a circle, ellipse, square, or rectangle.

7. The apparatus of claim 1, wherein at least one of the first surface and the second surface comprises a flexible material capable of resiliently flexing away from and toward the other surface in response to changes in pressure locally within the fluid chamber resulting from centrifugal and centripetal movement of the fluid in the fluid chamber.

8. The apparatus of claim 7, further comprising a compression inducing mechanism.

9. The apparatus of claim 7, further comprising a tension inducing mechanism.

10. The apparatus of claim 7, further comprising a movable localized compression inducing mechanism, a movable localized tension inducing mechanism, a generalized shear inducing mechanism, or a combination thereof.

11. The apparatus of claim 10, wherein at least one of the first surface and the second surface comprises a flexible material and wherein the flexible material comprises a sheet, film, or membrane.

12. The apparatus of claim 11, wherein the thin sheet, film, or membrane comprises a biocompatible material.

13. The apparatus of claim 12, wherein the thin sheet, film, or membrane is selected from the group consisting of polypropylene, polyethylene, a cellulosic material, and silicon.

14. The apparatus of claim 1, wherein at least one of the first surface and the second surface comprises fused silica, glass, plastic, metal, or silicon.

15. The apparatus of claim 1, additionally comprising a seal between the inner face of the first surface and the inner face of the second surface.

16. The apparatus of claim 15, wherein the seal is flexible.

17. The apparatus of claim 1, additionally comprising a plurality of chemical, biochemical, or biological moieties attached to at least one of the inner face of the first surface or the inner face of the second surface.

18. The apparatus of claim 17, wherein the chemical, biochemical, or biological moieties are selected from the group consisting of DNA, RNA, proteins, reagents, and combinations, derivatives, and modifications thereof.

19. The apparatus of claim 18, wherein the density of chemical, biochemical, or biological moieties is greater than about 100 per square micron.

20. The apparatus of claim 19 wherein the density of chemical, biochemical, or biological moieties is greater than about 5,000 per square micron.

21. The apparatus of claim 1 additionally comprising a plurality of dyes, labels, tags, reagents, or modifications, derivatives, or combinations thereof, attached to at least one of the inner face of the first surface or the inner face of the second surface.

22. The apparatus of claim 1 additionally comprising an environmental controller which maintains or controls the environmental conditions within the fluid chamber.

23. The apparatus of claim 22, wherein the environmental controller comprises a temperature controller.

24. The apparatus of claim 1, wherein the apparatus is adapted for automated use.

25. The apparatus of claim 1, wherein the apparatus comprises multiple fluid chambers.

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

introducing into an apparatus according to claim 1 at least one reactive chemical, biochemical, or biological fluid;

mixing the fluid; and

consecutively or simultaneously reacting the fluid.

27. The apparatus of claim 26, wherein the fluid is a chemical, biochemical, or biological fluid.

28. The method of claim 26, wherein the fluid chamber has a thickness of less than about 100 microns.

29. The method of claim 28, wherein the volume of fluid introduced into the fluid chamber is less than about 150 microliters.

30. The method of claim 26, said apparatus further comprising a movable localized compression inducing mechanism, a movable localized tension inducing mechanism, a generalized shear inducing mechanism, or a combination thereof.

31. The method of claim 30, additionally comprising an environmental controller which maintains or controls the environmental conditions within the fluid chamber.

32. The method of claim 30, wherein the method is automated.