Method for mixing a film of fluid

• US 8,012,765 B2
• Filed: 04/02/2010
• Issued: 09/06/2011
• 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): Gakh; Yelena G
• Application Number:
  US12/753,777
• Publication Number:
  US 20100248982A1
• Time in Patent Office: 522 Days
• Field of Search: None
• US Class Current: 436/174
• 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. A method for mixing a film of fluid, comprising:

providing a first substrate and a second substrate having inner surfaces and a seal that define a closed chamber up to several millimeters in thickness therebetween, said closed chamber adapted to retain a quantity of fluid so that the fluid is in contact with both inner surfaces, and wherein at least one of said inner surfaces is functionalized with polynucleotides, polypeptides, or polysaccharides;

introducing a fluid containing a plurality of components so as to provide a quantity of fluid in contact with both inner surfaces;

providing a bubble in the fluid using a discrete, controllable heat source; and

moving the provided bubble within the fluid in the closed chamber to result in mixing.

2. A method according to claim 1, wherein the polynucleotide is a polyribonucleotide.

3. A method according to claim 2, wherein the chamber is adapted to retain a film of fluid in contact with both inner surfaces.

4. A method according to claim 1, wherein the inner surfaces of the first and second substrates are substantially parallel.

5. A method according to claim 1, wherein the chamber is up to three millimeters in thickness.

6. A method according to claim 1, wherein the chamber is up to two millimeters in thickness.

7. A method according to claim 1, wherein the bubble is moved within the closed chamber using a plurality of discrete heat sources that create a temperature gradient in said fluid.

8. A method according to claim 7, wherein said discrete sources are resistors.

9. A method of claim 7, wherein the heat sources are positioned adjacent an inner surface of at least one of the first and second surfaces.

10. A method of claim 9, wherein the heat sources comprises resistors arranged in a predetermined pattern.

11. The method of claim 1, wherein the at least one of said inner surfaces is functionalized with polynucleotides.

12. The method of 1, wherein the at least one of said inner surfaces is functionalized with polypeptides.

13. A method for mixing a film of fluid comprising:

providing a first substrate and a second substrate having inner surfaces and a seal that define a closed chamber up to several millimeters in thickness therebetween, said chamber adapted to retain a quantity of fluid so that the fluid is in contact with both inner surfaces, and wherein at least one of said inner surfaces is functionalized with an array of RNA or DNA probes;

introducing a fluid sample containing DNA or RNA so as to provide a quantity of fluid in contact with both inner surfaces;

providing a bubble in the fluid using a discrete, controllable heat source;

moving a bubble within the fluid in the closed chamber to result in mixing;

after hybridization is complete, removing the sample from the apparatus; and

analyzing the functionalized inner surface for DNA or RNA that has hybridized.

14. A method according to claim 13, additionally comprising heating the DNA or RNA containing sample fluid while in the closed chamber.

15. A method according to claim 13, additionally comprising washing the functionalized inner surface prior to the analyzing.

16. A method according to claim 13, wherein the bubble is moved in a circular pattern.