Method of making a microbead array with attached biomolecules

• US 20070259449A1
• Filed: 06/11/2007
• Published: 11/08/2007
• Est. Priority Date: 04/25/1996
• Status: Active Grant

• Current Assignee: BioArray Solutions Limited (Werfen SA)
• Original Assignee: BioArray Solutions Limited (Werfen SA)
• Inventors: Seul, Michael
• Granted Patent: US 8,309,368 B2
• Time in Patent Office: Days
• US Class Current: 436/501
• 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 particulates 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 relics 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 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 method of making a bead array comprising a) contacting a substrate with a surface comprising discrete sites at a density of at least 100 sites per 1 mm², with a solution comprising a population of different beads, wherein said beds do not comprise an optical signature, and b) applying energy to said substrate or said solution, or both, such that at least a subpopulation of said different beads randomly associate onto sites.

2. A method according to claim 1 where in said energy is in the form of agitation.

8. The method according to claim 1, wherein said population of different beads comprises at least a first and second subpopulation.

9. The method according to claim 8, wherein said first and second subpopulation each comprise a different bioactive agent.

10. The method according to claim 9, wherein said bioactive agent comprises a protein.

11. The method according to claim 9, wherein said bioactive agent comprises a nucleic acid.

12. The method according to claim 11, wherein said nucleic acid comprises DNA.

13. The method according to claim 9, wherein said first and second subpopulations of beads each comprise a different identifier binding ligand.

14. The method according to claim 13, wherein said identifier binding ligand comprises a protein.

15. The method according to claim 13, wherein said identifier binding ligand comprises a nucleic acid.

16. The method according to claim 13 further comprising decoding a location of said bioactive agent on said array by correlating said bioactive agent with said location, whereby said decoding comprises contacting said array with at least first and second different decoder binding ligands, whereby said first and second decoder binding ligands bind to first and second identifier binding ligands, whereby said first and second identifier binding ligands identify said first and second bioactive agents, respectively, to thereby identify a location of said first and second bioactive agents to thereby decode said array.

17. The method according to claim 16, wherein said decoder binding ligands comprise proteins.

18. The method according to claim 16, wherein said decoder binding ligands comprise nucleic acids.

19. The method according to claim 1, wherein said substrate comprises a flat planar substrate.

3. A method of determining the presence of a target analyte in a sample comprising:

a) contacting said sample with an array comprising;

i) substrate with a surface comprising discrete sites at a density of at least 100 sites per 1 mm², wherein said sites are wells; and

ii) a population of microspheres randomly distributed on said sites, wherein said population comprises at least a first and a second subpopulation each comprising;

(a) a different bioactive agent; and

(b) a different identifier binding ligand;

b) determining the presence or absence of said target analyte; and

c) decoding a location of said bioactive agent by correlating said bioactive agent with said location, whereby said decoding comprises contacting said array with at least first and second different decoder binding ligands, whereby said first and second decoder binding ligands bind to a first and second identifier binding ligands, whereby said first and second identifier binding ligands identify said first and second bioactive agents, respectively, to thereby identify a location of said first and second bioactive agents to thereby decode said array.

4. The method according to claim 3, wherein said first and second bioactive agents comprise nucleic acids.

5. The method according to claim 4, wherein said nucleic acids comprise DNA.

6. The method according to claim 4, wherein said nucleic acids comprise single stranded nucleic acids.

7. The method according to claim 3, wherein said first and second bioactive agents comprise proteins.

20. The method according to claim 3, wherein said identifier binding ligands comprise proteins.

21. The method according to claim 3, wherein said identifier binding ligands comprise nucleic acids.

22. The method according to claim 3, wherein comprise decoder binding ligands are proteins.

23. The method according to claim 3, wherein comprise decoder binding ligands are nucleic acids.

24. The method according to claim 3, wherein said substrate comprises a flat planar substrate.