Method and apparatus for solid state molecular analysis

• US 6,573,369 B2
• Filed: 05/18/2000
• Issued: 06/03/2003
• Est. Priority Date: 05/21/1999
• Status: Expired due to Fees

• Current Assignee: BioForce Nanosciences, Inc.
• Original Assignee: BioForce Nanosciences, Inc.
• Inventors: Mosher, Curtis, Henderson, Eric, Lynch, Michael P.
• Primary Examiner(s): FREDMAN, JEFFREY NORMAN
• Application Number:
  US09/574,519
• Publication Number:
  US 20010051337A1
• Time in Patent Office: 1,111 Days
• Field of Search: 204/400, 204/403, 204/412, 536/23.1, 536/24.3, 435/6, 435/91.1, 530/300, 530/350
• US Class Current: 536/23.1
• CPC Class Codes: C12Q 1/6834 Enzymatic or biochemical coupling of nucleic acids to a solid phase
• CPC Class Codes: C12Q 1/6837 using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C12Q 2565/501 being an array of oligonucleotides
• CPC Class Codes: C12Q 2565/601 being a microscope, e.g. atomic force microscopy [AFM]
• CPC Class Codes: G01N 33/543 with an insoluble carrier for immobilising immunochemicals
• CPC Class Codes: Y10S 977/853 Biological sample
• CPC Class Codes: Y10S 977/858 including positioning/mounting nanostructure

Abstract

The invention is a method for the formation and analysis of novel miniature deposition domains. These deposition domains are placed on a surface to form a molecular array. The molecular array is scanned with an AFM to analyze molecular recognition events and the effect of introduced agents on defined molecular interactions. This approach can be carried out in a high throughput format, allowing rapid screening of thousands of molecular species in a solid state array. The procedures described here have the added benefit of allowing the measurement of changes in molecular binding events resulting from changes in the analysis environment or introduction of additional effector molecules to the assay system. The processes described herein are extremely useful in the search for compounds such as new drugs for treatment of undesirable physiological conditions. The method and apparatus of the present invention does not require the labeling of the deposition material or the target sample and may also be used to deposit large size molecules without harming the same.

Claims

1. A molecular array for characterizing molecular interaction events, comprising:

(a) a substrate; and

(b) at least one discrete molecular deposition domain on said substrate wherein the spatial address of the domain is less than one micron squared in area and each domain includes a biomolecule deposited on the substrate at a pre-selected location.

2. The molecular array of claim 1 wherein the at least one molecular deposition domain is a line.

3. The molecular array of claim 1 wherein the at least one molecular deposition domain is a spot.

4. The molecular array of claim 1 wherein the at least one molecular deposition domain is an irregular shape.

5. The molecular array of claim 1 wherein the at least one molecular deposition domain is a regular shape.

6. The molecular array of claim 1 wherein the at least one deposition domain is deposited at a known location.

7. The molecular array of claim 1 wherein the molecular deposition domains are affixed to the surface in a high density format.

8. The molecular array of claim 1 wherein the substrate is modified by one or more of the group consisting of gold, an amino group, a carboxyl group, and polymers.

9. The molecular array of claim 1 wherein the substrate is chosen from the group consisting of hydrophobic materials and hydrophilic materials.

11. The molecular array of claim 1 wherein the biomolecule is a protein.

12. The molecular array of claim 1 wherein the biomolecule is an antibody.

13. The molecular array of claim 1 wherein the biomolecule is a nucleic acid.

14. The molecular array of claim 1 wherein the biomolecule is a succinimide.

15. The molecular array of claim 1 wherein the biomolecule is a DNA molecule.

16. The molecular array of claim 1 wherein the biomolecule is an RNA molecule.

32. The molecular array of claim 1, wherein the array comprises more than one molecular deposition domain, and wherein the biomolecule is selected from the group consisting of a protein, an antibody, a nucleic acid, a succinimide, a DNA molecule, an RNA molecule, and combinations thereof.

10. A method for the processing of an array comprising:

(a) forming an array on a substrate, the array comprising a plurality of deposition domains formed of a deposition material at a pre-selected location;

(b) exposing the array to one or more materials which contain an at least one target sample that causes a molecular interaction event with one or more of the deposition samples; and

(C) scanning the array utilizing a scanning probe microscope to characterize the molecular interaction events that have occurred between the target samples and the deposition material.

17. A molecular array for characterizing molecular interaction events, comprising:

(a) a substrate; and

(b) at least one discrete molecular deposition domain on said substrate wherein the spatial address of the domain is less than one micron squared in area and each domain includes a silane deposited on the substrate at a pre-selected location.

18. An array for the identification of a target material comprising:

a substrate including a substantially flat surface; and

an at least one discrete deposition domain deposited on said surface, said deposition domain being smaller than one micron squared in total area and deposited at a pre-selected location on the surface, the deposition domain including a long chain biomolecular deposition material having the capacity to bind the target material.

19. The array of claim 18 wherein the deposition material is a protein.

20. The array of claim 18 wherein the deposition material is an antibody.

21. The array of claim 18 wherein the deposition material is a nucleic acid.

22. The array of claim 18 wherein the deposition material is a DNA molecule.

23. The array of claim 18 wherein the surface is chosen from one or more of the group consisting of a hydrophobic surface and a hydrophilic surface.

24. The array of claim 18 wherein the substantially flat surface further comprise a sputter deposited layer of gold thereon, the deposition domain deposited on the gold.

25. An array of deposition domains for the detection of one or more pre-determined target materials comprising:

a solid glass substrate including a substantially flat surface; and

an at least one discrete domain deposited on the surface of the substrate, each domain being deposited at a known location and being smaller than one micron squared in area, each domain further including at least one type of molecule with a binding affinity for one or more of the target materials, at least two domains containing different biologically or chemically based molecules.

26. The array of claim 25 wherein the molecule is chosen from one or more of the group consisting of a protein, antibody, nucleic acid, and DNA.

27. The array of claim 25 wherein the surface is modified.

28. A molecular array for characterizing molecular interaction events, comprising:

(a) a substrate; and

(b) at least one molecular deposition domain on said substrate wherein the spatial address of the domain is less than one micron squared in area, each domain includes a biologically or chemically based molecule directly deposited on the substrate at a pre-selected location, at least two domains containing different biologically or chemically based molecules.

29. The array of claim 28 wherein the substrate is chosen from one or more of the group consisting of mica, glass, silicon, and quartz.

30. A molecular array for characterizing molecular interaction events, comprising:

(a) a substrate; and

(b) at least one molecular deposition domain on said substrate wherein the spatial address of the domain is less than one micron squared in area, each domain includes a biologically or chemically based molecule directly deposited on the substrate at a pre-selected location, and wherein the molecular deposition domain interacts with a molecular deposition probe having at least one microsphere attached thereto.

31. The array of claim 30 wherein the substrate includes a surface chosen from one or more of the group consisting of mica, glass, silicone, tetrafluoroethylene, polystyrene, polycarbonate, and polypropylene.