Method and apparatus for solid state molecular analysis

• US 6,998,228 B2
• Filed: 06/25/2002
• Issued: 02/14/2006
• Est. Priority Date: 05/21/1999
• Status: Expired due to Fees

• Current Assignee: BioForce Nanosciences, Inc.
• Original Assignee: BioForce Nanosciences, Inc.
• Inventors: Henderson, Eric, Mosher, Curtis, Lynch, Michael P.
• Primary Examiner(s): FREDMAN, JEFFREY NORMAN
• Application Number:
  US10/179,102
• Publication Number:
  US 20030013111A1
• Time in Patent Office: 1,330 Days
• Field of Search: 435/4, 435/6, 435/7.1
• US Class Current: 435/4
• 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 method for the construction of a molecular deposition domain on a surface, comprising:

(a) providing a surface;

(b) depositing a deposition material on a deposition device, wherein the deposition material comprises a biomolecule;

(c) depositing the deposition material on the surface using said deposition device, forming a molecular deposition domain smaller than one micron squared.

4. The method of claim 1 wherein depositing the deposition material on the deposition device comprises

contacting the deposition device with the deposition material retaining a portion of the deposition material on the deposition device , and

drying the deposition material on the deposition device.

5. The method of claim 1 wherein depositing the deposition material on said surface further comprises:

(d) placing the deposition device in a position adjacent to the surface;

(e) exposing the deposition device and the surface to a humid gas so that a capillary bridge is formed between the deposition device and the surface;

(f) withdrawing the deposition device from the position adjacent to the surface, leaving a portion of the deposition material on the surface in a deposition domain smaller than one micron squared.

6. The method of claim 5 wherein withdrawing the device further comprises exposing the deposition domain, the surface, and the deposition device to a dry gas to sever the capillary bridge.

7. The method of claim 1 wherein depositing the deposition material on said surface further comprises:

(a) touching the deposition device with the deposition material on it to the surface;

(b) exposing the deposition device and surface to a humid gas so that a capillary bridge forms between the deposition device and the surface;

(c) retracting the deposition device from the surface leaving a deposition domain on the surface.

8. The method of claim 7 wherein withdrawing the device further comprises exposing the deposition domain, the surface, and the deposition device to a dry gas to sever the capillary bridge.

10. The method of claim 1 wherein providing the surface further comprises chemically modifying said surface with a reactive material.

11. The method in claim 1 wherein the molecular deposition domain is a line.

12. The method in claim 1 wherein the molecular deposition domain is a spot.

13. The method in claim 1 wherein the molecular deposition domain is an irregular shape.

14. The method in claim 1 wherein the molecular deposition domain is a regular shape.

15. The method of claim 1 wherein said surface is chosen from one or more of the group consisting of a hydrophobic surface, a hydrophilic surface, and a chemically modified surface.

16. The method of claim 1 wherein said surface is chosen from one or more of the group consisting of a polymer and a metal.

17. The method of claim 1 wherein preparing said surface further comprises modifying the surface with one or more of the group consisting of an amino group and a carboxyl group.

18. The method of claim 1 wherein said surface is physically modified.

19. The method of claim 1 wherein said surface is physically modified with a metal.

20. The method of claim 1 wherein said surface is chosen from one or more of the group consisting of mica, silicon, glass, and quartz.

21. The method of claim 1 wherein said deposition material is chosen from one or more of the group consisting of proteins, antibodies, nucleic acids, DNA, and RNA.

22. The method of claim 1 in which said deposition material comprises long chain molecules.

23. The method of claim 1 wherein the surface comprises a chemically modified surface and wherein the deposited deposition material is immobilized.

24. The method of claim 23 wherein the immobilized deposition material is chosen from one or more of the group consisting of a nucleic acids, a proteins, a lipids, and a sugar.

25. The method of claim 23 wherein the deposition device is a scanning probe microscope probe.

32. The method of claim 1 wherein the deposition device is controlled by a computer.

33. The method of claim 1 wherein depositing the deposition material on the deposition device further comprises regulating the humidity surrounding the deposition device and the surface.

34. The method of claim 1 wherein the surface of step (a) comprises activated chemical groups.

35. The method of claim 34 wherein the chemical groups are activated from an energy source in the far field.

36. The method of claim 34 wherein the chemical groups are activated from an energy source in the near field.

37. The method of claim 34 wherein the surface is photosensitive.

40. The method of claim 1, wherein the biomolecule comprises histidine and wherein the surface comprises nickel.

41. The method of claim 1, wherein the biomolecule comprises a sulfhydryl group and wherein the surface comprises gold.

42. The method of claim 1 further comprising drying the deposition material on the deposition device of step (b).

2. A method for the construction of a molecular deposition domain on a surface, comprising:

(a) providing a surface;

(b) placing a deposition device in contact with or near proximity to a deposition material to be deposited;

(c) exposing the deposition device and the deposition material to a humid gas so that a capillary bridge is formed between the deposition device and the deposition material;

(d) retracting the deposition device, retaining a portion of the deposition material on the deposition device;

(e) depositing the deposition material on the surface using said deposition device, forming a molecular deposition domain smaller than one micron squared.

3. The method of claim 2 further comprising drying the deposition material on the deposition device of step (d).

9. A method for the construction of a molecular deposition domain on a surface, comprising:

(a) providing a surface wherein the surface comprises a sputtered layer of gold;

(b) depositing a deposition material on a deposition device;

(c) depositing the deposition material on the surface using said deposition device, forming a molecular deposition domain smaller than one micron squared.

26. A method for the construction of a molecular deposition domain on a surface, comprising:

(a) providing a surface;

(b) depositing a deposition material on a deposition device wherein the deposition device further comprises an attached microsphere;

(c) depositing the deposition material on the surface using the deposition device, forming a molecular deposition domain.

27. The method of claim 26 wherein the microsphere is up to 25 microns in diameter.

28. The method of claim 26 wherein the microsphere is larger than 25 microns in diameter.

29. The method of claim 26 wherein the microsphere comprises a non-porous material.

30. The method of claim 26 in which the microsphere comprises a porous material.

31. The method of claim 26 in which the microsphere comprises glass.

43. The method of claim 26, wherein the deposition domain is smaller than one micron squared.

44. The method of claim 26, wherein the deposition material comprises a biomolecule.

38. A method for constructing an array of molecular deposition domains comprising:

(a) providing a surface;

(b) providing an at least one deposition material;

(c) depositing a first deposition material on a deposition device;

(d) depositing the first deposition material on the surface in a known position, forming a first molecular deposition domain smaller than one micron squared in total area;

(e) cleaning the deposition device;

(f) repeating the above steps to form an at least one other deposition domain, creating an array of two or more deposition domains on said surface.

39. The method of claim 38 wherein cleaning the deposition device comprises sonication.