Bioarray chip reaction apparatus and its manufacture

• US 7,364,895 B2
• Filed: 08/11/2003
• Issued: 04/29/2008
• Est. Priority Date: 06/08/1994
• Status: Expired due to Fees

• Current Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Winkler, James L., Goss, Virginia W., Besemer, Donald M.
• Primary Examiner(s): Horlick; Kenneth R.
• Assistant Examiner(s): Tung; Joyce
• Application Number:
  US10/639,696
• Publication Number:
  US 20050191630A1
• Time in Patent Office: 1,723 Days
• Field of Search: 435/286.7, 435/288.3, 366/261, 366/183.3, 422/102
• US Class Current: 435/266
• CPC Class Codes: B01F 33/252 using bubbles as loose mixing element
• 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: B01F 33/45 Magnetic mixers; Mixers with magnetically driven stirrers
• CPC Class Codes: B01F 33/452 using independent floating stirring elements
• 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 2219/00286 Reactor vessels with top and bottom openings
• CPC Class Codes: B01J 2219/00353 Pumps
• CPC Class Codes: B01J 2219/00371 comprising electrodes
• CPC Class Codes: B01J 2219/00432 Photolithographic masks
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00529 DNA chips
• CPC Class Codes: B01J 2219/00531 essentially square
• CPC Class Codes: B01J 2219/00536 in the shape of disks
• CPC Class Codes: B01J 2219/0054 Means for coding or tagging the apparatus or the reagents
• CPC Class Codes: B01J 2219/00547 Bar codes
• CPC Class Codes: B01J 2219/00585 Parallel processes
• 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 2219/00608 : DNA chips
• CPC Class Codes: B01J 2219/0061 : The surface being organic
• CPC Class Codes: B01J 2219/00612 : the surface being inorganic
• CPC Class Codes: B01J 2219/00621 : by physical means, e.g. trenches, raised areas
• CPC Class Codes: B01J 2219/00626 : Covalent
• 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 2219/00662 : Two-dimensional arrays within two-dimensional arrays
• CPC Class Codes: B01J 2219/00689 : using computers
• CPC Class Codes: B01J 2219/00695 : Synthesis control routines, e.g. using computer programs
• CPC Class Codes: B01J 2219/00711 : Light-directed synthesis
• CPC Class Codes: B01J 2219/00722 : Nucleotides
• CPC Class Codes: B01J 2219/00725 : Peptides
• CPC Class Codes: B01J 2219/00731 : Saccharides
• CPC Class Codes: B01L 2200/025 : Align devices or objects to ensure defined positions relative to each other
• CPC Class Codes: B01L 2200/027 : for microfluidic devices
• CPC Class Codes: B01L 2200/0689 : Sealing
• CPC Class Codes: B01L 2200/12 : Specific details about manufacturing devices
• CPC Class Codes: B01L 2200/147 : Employing temperature sensors
• CPC Class Codes: B01L 2300/0636 : Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0816 : Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0819 : Microarrays; Biochips
• CPC Class Codes: B01L 2300/0825 : Test strips
• CPC Class Codes: B01L 2300/0877 : Flow chambers
• CPC Class Codes: B01L 2300/1805 : Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
• CPC Class Codes: B01L 2400/0439 : ultrasonic vibrations, vibrating piezo elements
• CPC Class Codes: B01L 2400/0442 : thermal energy, e.g. vaporisation, bubble jet
• CPC Class Codes: B01L 2400/0487 : fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0611 : duck bill valves
• CPC Class Codes: B01L 2400/065 : sliding valves
• CPC Class Codes: B01L 3/5027 : by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• 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 3/502715 : characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 9/52 : Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
• CPC Class Codes: B01L 9/527 : for microfluidic devices, e.g. used for lab-on-a-chip
• CPC Class Codes: B82Y 30/00 : Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C07H 21/00 : Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• 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 40/12 : Libraries containing saccharides or polysaccharides, or derivatives thereof
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: C40B 70/00 : Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes
• CPC Class Codes: G01N 2035/00158 : Elements containing microarrays, i.e. "biochip"
• CPC Class Codes: H01L 21/67144 : Apparatus for mounting on conductive members, e.g. leadframes or conductors on insulating substrates
• CPC Class Codes: Y10T 436/25 : including sample preparation

Abstract

A body 300 having a cavity 310 for mounting a substrate 120 fabricated with probe sequences at known locations according to the methods disclosed in U.S. Pat. No. 5,143,854 and PCT WO 92/10092 or others, is provided. The cavity includes inlets 350 and 360 for introducing selected fluids into the cavity to contact the probes. Accordingly, a commercially feasible device for use in high throughput assay systems is provided.

Claims

1. An apparatus for mixing a fluid, the apparatus comprising:

a first substrate comprising a first inner surface functionalized with a microarray of reactive moieties;

a substantially parallel second substrate also comprising a second inner surface, wherein said first and second inner surfaces bound a closed chamber there between, said chamber adapted to retain a quantity of fluid so that the fluid is in contact with both surfaces;

at least one bubble disposed within said chamber; and

means for moving the chamber so that the bubble moves relative to the fluid so effect mixing of the fluid.

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

3. The apparatus of claim 1, wherein the bubble comprises a gas.

4. The apparatus of claim 1, wherein the bubble comprises nitrogen.

5. The apparatus of claim 1, wherein the babble is produced by introducing a volume of the fluid that is Jess than she total volume of the closed chamber.

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

7. The apparatus of claim 1, further comprising means for introducing fluid into the closed chamber.

8. The apparatus of claim 1, wherein the first substrate and the second substrate are individually comprised of a material selected from the group consisting of glass, silicon, fused silica, plastic and a combination thereof.

9. The apparatus of claim 1, wherein the first substrate is comprised of glass.

10. The apparatus of claim 1, wherein the means for moving the bubble is selected from the group consisting of rotating the apparatus about an axis, rolling the apparatus, and reciprocally shaking the apparatus.

11. A method for mixing a fluid, comprising:

providing an apparatus according to claim 1, introducing a fluid into the closed chamber;

introducing a bubble within the fluid; and

moving the bubble in the fluid to effect mixing of the fluid.

12. A method for mixing a fluid, comprising:

providing an apparatus according to claim 2, introducing a fluid into the closed chamber, introducing a bubble within the fluid; and

moving the bubble in the fluid to effect mixing of the fluid.

13. A method for mixing a fluid, comprising:

providing an apparatus according to claim 3, introducing a fluid into the closed chamber, introducing a bubble within the fluid; and

moving the bubble in the fluid to effect mixing of the fluid.

14. A method for mixing a fluid, comprising:

providing an apparatus according to claim 10, introducing a fluid into the closed chamber;

introducing a bubble within the fluid; and

moving the bubble in the fluid to effect mixing of the fluid.

15. An apparatus for mixing a fluid, the apparatus comprising:

a first substrate comprising a first inner surface functionalized with an array of reactive moieties;

a substantially parallel second substrate also comprising a second inner surface, wherein said first and second inner surfaces bound a closed chamber there between, said chamber adapted to retain a quantity of fluid so that the fluid is in contact with both surfaces;

at least one bubble disposed within said chamber; and

means for moving the chamber so that the bubble moves relative to the fluid to effect mixing of the fluid.

16. The apparatus of claim 15, wherein the closed chamber has a thickness of less than about 2 millimeters.

17. The apparatus of claim 15, wherein the bubble comprises a gas.

18. The apparatus of claim 15, wherein the bubble comprises a gas selected from the group consisting of air, nitrogen, argon, or oxygen.

19. The apparatus of claim 15, wherein the bubble is produced by introducing a volume of the fluid that is less than the total volume of the closed chamber.

20. The apparatus of claim 15, further including a flexible seal between the inner surface of the first substrate and the inner surface of the second substrate.

21. The apparatus of claim 15, further comprising means for introducing fluid into the closed chamber.

22. The apparatus of claim 15, wherein the first substrate and The second substrate are individually comprised of a material selected from the group consisting of glass, silicon, fused silica, plastic, ceramic, and metal, and a combination thereof.

23. The apparatus of claim 15, wherein the first substrate and the second substrate are individually comprised of glass.

24. The apparatus of claim 15, wherein the means for moving the babble is selected from the group consisting of rotating the apparatus about an axis, rolling the apparatus, and reciprocally shaking the apparatus.

25. A method for mixing a fluid, comprising:

providing an apparams according to claim 15, introducing a fluid into the closed chamber;

introducing a bubble within the fluid; and

moving the bubble in the fluid to effect mixing of the fluid.

26. A method for mixing a fluid, comprising:

providing an apparatus according to claim 16, introducing a fluid into the closed chamber;

introducing a bubble within the fluid; and

moving the bubble in the fluid to effect mixing of the fluid.

27. A method for mixing a fluid, comprising:

providing an apparatus according to claims 17, introducing a fluid into the closed chamber;

introducing a bubble within the fluid; and

moving the bubble in the fluid to effect mixing of the fluid.

28. A method for mixing a fluid, comprising:

providing an apparatus according to claim 24, introducing a fluid into the closed chamber;

introducing a bubble within the fluid; and

moving the bubble in the fluid to effect mixing of the fluid.