Method of making a microbead array with attached biomolecules

• US 8,691,594 B2
• Filed: 10/31/2012
• Issued: 04/08/2014
• 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): Nguyen, Bao Thuy L
• Assistant Examiner(s): Do, Pensee
• Application Number:
  US13/664,953
• Publication Number:
  US 20130123146A1
• Time in Patent Office: 524 Days
• Field of Search: 436/518, 436/525, 436/534, 436/528, 436/63, 436/164, 436/165, 436/172
• US Class Current: 436/518
• 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 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 method of making a bead array comprising:

a) contacting a substrate having a planar surface with a suspension comprising populations of several differently-encoded beads having diameters of up to 10 microns, wherein each population of differently-encoded beads has a different biomolecule attached thereto and wherein at least a portion of the biomolecules are bound to an analyte of interest; and

b) applying energy to said substrate or said suspension, or both, such that the populations of differently-encoded beads form an ordered array on the planar surface and the beads are at pre-determined distances from each other.

2. The method according to claim 1 wherein the biomolecule is a protein or an oligonucleotide.

3. The method according to claim 1 wherein the beads are in a planar crystalline arrangement.

4. The method according to claim 1 wherein the beads are in a hexagonally crystalline configuration.

5. The method according to claim 1 wherein the beads are in a bubble raft arrangement.

6. The method according to claim 1 wherein the beads are encoded using oligonucleotides.

7. The method according to claim 1 wherein the beads are binary encoded.

8. The method according to claim 1 wherein the substrate has a patterned surface.

9. The method according to claim 1 wherein the ordered array of beads comprises subarrays of beads.

10. The method according to claim 1 wherein the beads have a 2-10 micron diameter.

11. The method according to claim 1 wherein the beads range in size from approximately 100 Angstroms to 10 microns.

12. The method according to claim 1 wherein the energy is a magnetic field.

13. The method according to claim 1 wherein the energy is electrical energy.

14. The method according to claim 1 wherein the beads are magnetic.

15. A method of making a bead array comprising:

a) contacting a substrate having a planar surface with a suspension comprising populations of several differently-encoded beads having diameters of up to 10 microns, wherein each population of differently-encoded beads has a different biomolecule attached thereto, such that the encoding of each bead corresponds uniquely to the biomolecule attached thereto; and

b) applying energy to said substrate or said suspension, or both, such that the populations of differently-encoded beads form an ordered array on the planar surface and the beads are at pre-determined distances from each other.

16. The method according to claim 15 wherein the beads are immobilized to the substrate following step b).

17. The method according to claim 16 wherein the beads are immobilized by anchoring to the substrate.

18. The method according to claim 16 wherein the beads are immobilized by chemical attachment, heterobifunctional cross-linking agents, or physical attraction to the substrate.

19. The method according to claim 18 wherein physical attraction is through van der Waals forces.

20. The method according to claim 15 wherein the biomolecule is a protein or an oligonucleotide.