Deposition of metal oxides onto surfaces as an immobilization vehicle for carboxylated or phophated particles or polymers

• US 8,173,198 B2
• Filed: 07/23/2009
• Issued: 05/08/2012
• Est. Priority Date: 07/23/2008
• Status: Active Grant

• Current Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Original Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: Menchen, Steven M., Inman, Christina E., Taing, Meng, Fry, George A.
• Primary Examiner(s): Riley, Jezia
• Application Number:
  US12/508,539
• Publication Number:
  US 20100086927A1
• Time in Patent Office: 1,020 Days
• Field of Search: 427/2.13, 427/453, 435/174, 530/810, 424/9.322, 536/23.1
• US Class Current: 427/2.13
• CPC Class Codes: C07F 9/093 Polyol derivatives esterified at least twice by phosphoric acid groups
• CPC Class Codes: C07F 9/6596 having atoms other than oxygen, sulfur, selenium, tellurium, nitrogen or phosphorus as ring hetero atoms
• CPC Class Codes: C12Q 1/6834 Enzymatic or biochemical coupling of nucleic acids to a solid phase
• CPC Class Codes: Y10S 530/81 Carrier - bound or immobilized peptides or proteins and the preparation thereof, e.g. biological cell or cell fragment as carrier

Abstract

Intermediates and methods for forming activated metal complexes bound to surfaces on oxide layers, immobilizing beads to the modified surface and articles produced thereby are described. Hydroxyl groups on the oxide surfaces are reacted with a metal reagent complex of the formula Y(L-Pol)_m, where Y is a transition metal, magnesium or aluminum, L is oxygen, sulfur, selenium or an amine, and “Pol” represents a passivating agent such as a methoxyethanol, a polyethylene glycol, a hydrocarbon, or a fluorocarbon. The resulting modified surface can be further reacted with a passivating agent having a phosphate functional group or a plurality of functional groups that are reactive with or that form complexes with Y. The metal oxide surfaces exhibit minimal binding to bio-molecules, exhibit uniform deposition and immobilization of beads at high density, can be subsequently modified to create surfaces having a variety of properties, and can be used for nucleic acid sequencing and other analyses and in single-molecule detection schemes.

Claims

1. A method of immobilizing a particle onto a surface comprising:

depositing a metal oxide layer onto the surface; and

contacting a functionalized particle onto the metal oxide surface, the particle selected from the group consisting of a bead, a refractory bead, and a ligation bead;

wherein the particle is immobilized on the surface.

2. The method of claim 1, wherein the functionalized particle comprises phosphate moieties, carboxylated moieties or a combination thereof.

3. The method of claim 2, wherein the phosphate moieties are derived from phosphodiester linkages selected from the group consisting of a nucleic acid, an oligonucleotide or a biomolecule containing nucleic acids, carboxylates, phosphonates or phosphates.

4. The method of claim 1, wherein the surface is a glass, a metal, a metal oxide or an organic polymer.

5. The method of claim 1, wherein the particle is composed of a material selected from the group consisting of organic polymers, silicate polymers, alumina, titania, zirconia, and combinations thereof.

6. The method of claim 4, wherein the polymer is solid at operating temperatures.

7. The method of claim 4, wherein the polymer is optically transparent.

9. The method of claim 4, wherein the polymer is activated to comprise transition metal reactive groups.

10. The method of claim 9, wherein the reactive group is selected from hydroxyl, carboxyl, phosphate, phosphonate, silanol, alumina and oxides of transition metals.

11. The method of claim 1, wherein the surface comprises a material selected from the group consisting of silicon, aluminum, germanium, gallium, titanium, tantalum, indium, zirconium, magnesium, tin, gold, silver, hafnium, carbon and an organic polymer derivative.

12. The method of claim 4, wherein the polymer is selected from the group consisting of cyclic olefin polymer (COP), cyclic olefin co-polymer (COC), polypropylene, polycarbonate, fluorinated polyethylene, polymethyl methacrylate, polystyrene, polybutadiene, and blends thereof.

13. The method of claim 12, wherein the blend is a mixture of polystyrene, polypropylene and polybutadiene.

14. The method of claim 1 further comprising passivating the surface.

15. The method of claim 14, wherein the passivating comprises a passivating agent selected from the group consisting of poly(vinyl phosphoric acid), pyrophosphate, poly(acrylic acid), poly(vinyl alcohol), polyethylene glycol comprising functionalities of poly-phosphate-, poly-carboxylate-, or poly-hydroxyl- or combinations thereof and poly(N,N-dimethylacrylamide).

16. The method of claim 1, wherein the metal oxide comprises an organic polymer derivative.

18. The method of claim 1, wherein the particle includes an attached nucleic acid, oligonucleotide, or primer.

19. The method of claim 1, wherein the metal oxide layer comprises zirconium.

8. The method of claim , wherein the polymer is stable in a variety of solvent.

17. A method of immobilizing a particle onto a surface comprising:

depositing a metal oxide layer onto the surface; and

contacting a functionalized particle onto the metal oxide surface, the particle being at least 0.5 to 10 microns in size;

wherein the particle is immobilized on the surface.