Arrays formed of encoded beads having oligonucleotides attached

• US 7,615,345 B2
• Filed: 05/16/2006
• Issued: 11/10/2009
• Est. Priority Date: 04/25/1996
• Status: Expired due to Fees

• Current Assignee: BioArray Solutions Limited (Werfen SA)
• Original Assignee: BioArray Solutions Limited (Werfen SA)
• Inventors: Seul, Michael
• Primary Examiner(s): FORMAN, BETTY J
• Application Number:
  US11/436,009
• Publication Number:
  US 20060228739A1
• Time in Patent Office: 1,274 Days
• Field of Search: None
• US Class Current: 435/6.11
• 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 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00648 by the use of solid beads
• 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 2219/00713 Electrochemical synthesis
• CPC Class Codes: B01L 2200/0647 Handling flowable solids, e.g. microscopic beads, cells, particles
• CPC Class Codes: B01L 2200/0652 Sorting or classification of particles or molecules
• CPC Class Codes: B01L 2200/0663 Stretching or orienting elongated molecules or particles
• CPC Class Codes: B01L 2200/0668 Trapping microscopic beads
• 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 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/0877 Flow chambers
• CPC Class Codes: B01L 2300/089 Virtual walls for guiding liquids
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0427 Electrowetting
• CPC Class Codes: B01L 2400/0454 radiation pressure, optical tweezers
• 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: B01L 3/502761 : specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: C12Q 1/6825 : Nucleic acid detection involving sensors
• CPC Class Codes: C12Q 1/6837 : using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C12Q 2563/155 : Particles of a defined size, e.g. nanoparticles
• CPC Class Codes: C12Q 2565/501 : being an array of oligonucleotides
• CPC Class Codes: C12Q 2565/607 : being a sensor, e.g. electrode
• CPC Class Codes: C40B 40/00 : Libraries per se, e.g. arrays, mixtures
• CPC Class Codes: C40B 40/04 : Libraries containing only organic compounds
• CPC Class Codes: G01N 15/1468 : with spatial resolution of the texture or inner structure of the particle
• CPC Class Codes: G01N 15/149 : specially adapted for sorting particles, e.g. by their size or optical properties
• CPC Class Codes: G01N 2015/1497 : Particle shape
• CPC Class Codes: G01N 27/447 : using electrophoresis
• CPC Class Codes: G01N 33/54313 : the carrier being characterised by its particulate form
• CPC Class Codes: G01N 33/54386 : Analytical elements
• CPC Class Codes: G01N 33/6845 : Methods of identifying protein-protein interactions in protein mixtures
• CPC Class Codes: G02B 3/0012 : characterised by the manufacturing method
• CPC Class Codes: G02B 3/0056 : arranged along two different directions in a plane, e.g. honeycomb arrangement of lenses G02B3/0043 takes precedence; miniaturised objectives for electronic devices employing wafer level optics G02B13/0085
• CPC Class Codes: G02B 3/0075 : characterized by non-optical structures, e.g. having integrated holding or alignment means
• CPC Class Codes: H05H 3/04 : Acceleration by electromagnetic wave pressure
• CPC Class Codes: Y10S 435/808 : Optical sensing apparatus
• CPC Class Codes: Y10S 435/81 : Packaged device or kit
• CPC Class Codes: Y10S 435/814 : Enzyme separation or purification
• CPC Class Codes: Y10S 436/806 : Electrical property or magnetic property
• CPC Class Codes: Y10S 436/808 : Automated or kit
• CPC Class Codes: Y10S 436/809 : Multifield plates or multicontainer arrays
• CPC Class Codes: Y10T 436/25125 : Digestion or removing interfering materials

Abstract

A method and apparatus for the manipulation of colloidal particles and biomolecules at the interface between an insulating electrode such as silicon oxide and an electrolyte solution. Light-controlled electrokinetic assembly of particles near surfaces relies on the combination of three functional elements: the AC electric field-induced assembly of planar aggregates; the patterning of the electrolyte/silicon oxide/silicon interface to exert spatial control over the assembly process; and the real-time control of the assembly process via external illumination. The present invention provides a set of fundamental operations enabling interactive control over the creation and placement of planar arrays of several types of particles and biomolecules and the manipulation of array shape and size. The present invention enables sample preparation and handling for diagnostic assays and biochemical analysis in an array format, and the functional integration of these operations. In addition, the present invention provides a procedure for the creation of material surfaces with desired properties and for the fabrication of surface-mounted optical components.

Claims

1. A bead array comprising several planar assemblies of encoded beads each said assembly in a designated area on a substrate, wherein said encoded beads comprise a plurality of unique capture oligonucleotides and have a diameter of up to 10 microns, wherein the beads in said designated areas are arranged in rows and wherein the beads within the planar assemblies are in a planar hexagonal crystalline arrangement, and wherein a number of adjacent beads within the planar assemblies are encoded differently and have different oligonucleotides attached thereto, and other adjacent beads are encoded the same and have the same oligonucleotides attached thereto, said encoding allowing identification of the oligonucleotide attached thereto, and wherein differently encoded beads are randomly distributed within the planar assemblies.

8. The bead array of any of claims 1-4, wherein said designated area comprises an area of predetermined shape and/or size.

9. The bead array of any of claims 1 or 3 wherein said planar hexagonal crystalline arrangement is a bubble raft of densely packed beads.

10. The bead array of any of claims 1-4, wherein said beads are assembled into a plurality of designated areas.

11. The bead array of any of claims 1-4, wherein said substrate is a silicon substrate.

12. The bead array of claim 11, wherein said silicon substrate comprises a planar surface.

13. The bead array of claim 11, wherein the designated area on said silicon substrate is defined by lithographic patterning.

14. The bead array of claim 11, wherein the designated area on said silicon substrate is defined by chemical patterning.

15. The bead array of any of claims 1-4, wherein said planar assembly comprises a single layer of beads.

16. The bead array of any of claims 1-4, wherein said beads are comprised of latex.

17. The bead array of any of claims 1-4, wherein said beads are comprised of silica.

18. The bead array of any of claims 1-4, wherein said beads are comprised of oxide particles.

19. The bead array of any of claims 1-4, wherein said beads are comprised of polystyrene.

20. The bead array of any of claims 1-4, wherein said beads are chemically encoded.

21. The bead array of any of claims 1-3, wherein said beads are encoded by oligonucleotides.

22. The bead array of claims 1-2 or 4, wherein said beads have a diameter of about 2 microns.

2. A bead array comprising at least one planar assembly of encoded beads in a designated area on a substrate, wherein said encoded beads comprise a plurality of unique capture oligonucleotides and have a diameter of up to 10 microns, and within the planar assembly said beads are arranged to form planar crystals, and wherein a number of adjacent beads are encoded differently and have different oligonucleotides attached thereto, and other adjacent beads are encoded the same and have the same oligonucleotides attached thereto, said encoding allowing identification of the oligonucleotide attached thereto, and wherein differently-encoded beads are randomly distributed within said planar assembly.

26. The bead array of claim 2 wherein said planar crystals are bubble rafts of densely packed beads.

3. A bead array comprising at least one planar assembly of encoded beads in a designated area on a substrate, wherein said encoded beads comprise a plurality of unique capture oligonucleotides and have a diameter of up to 10 microns and the beads within the planar assembly are in a planar hexagonal crystalline arrangement, and wherein a number of adjacent beads are encoded differently and have different oligonucleotides attached thereto, and other adjacent beads are encoded the same and have the same oligonucleotides attached thereto, said encoding allowing identification of the oligonucleotide attached thereto, and wherein differently-encoded beads are randomly distributed within said planar assembly.

4. A bead array comprising several planar assemblies of encoded oligonucleotide-bearing beads, each said assembly in a designated area on a substrate, wherein said beads (a) are encoded by oligonucleotides, (b) comprise a plurality of unique capture oligonucleotides, (c) have diameters of up 10 microns, and wherein within the planar assemblies said beads are in a planar crystalline arrangement, and wherein a number of adjacent beads are encoded differently and have different oligonucleotides attached thereto, and other adjacent beads are encoded the same and have the same oligonucleotides attached thereto, said encoding allowing identification of the oligonucleotide attached thereto, and wherein differently-encoded beads are randomly distributed within said planar assembly.

5. The bead array of claim 4, wherein said capture oligonucleotides are capable of annealing to an at least partially complementary analyte.

6. The bead array of claim 5, wherein the analyte is a cDNA derived from mRNA by reverse transcription.

7. The bead array of claim 5, wherein the analyte is an amplicon derived from genomic DNA by amplification.

25. The bead array of claim 4 wherein said beads have a diameter from several hundred Angstroms up to 10 microns.

27. The bead array of claim 4 wherein said planar crystalline arrangement is a bubble raft of densely packed beads.

23. An array of arrays each comprising a plurality of bead arrays according to any of claims l-4.

24. The array of arrays according to claim 23, wherein each of said bead arrays is in a separate designated area on a substrate.