Combined molecular binding detection through force microscopy and mass spectrometry

• US 20030134273A1
• Filed: 07/17/2002
• Published: 07/17/2003
• Est. Priority Date: 07/17/2001
• Status: Abandoned Application

• Current Assignee: BioForce Nanosciences, Inc.
• Original Assignee: BioForce Nanosciences, Inc.
• Inventors: Henderson, Eric
• Application Number:
  US10/198,202
• Publication Number:
  US 20030134273A1
• Time in Patent Office: Days
• US Class Current: 435/5
• CPC Class Codes: B82Y 35/00 Methods or apparatus for measurement or analysis of nanostructures
• CPC Class Codes: G01Q 30/02 Non-SPM analysing devices, e.g. SEM [Scanning Electron Microscope], spectrometer or optical microscope
• CPC Class Codes: G01Q 60/42 Functionalisation

Abstract

The present invention includes a method for analyzing and characterizing molecular interaction events utilizing a combined scanning probe microscope (SPM) and a mass spectrometer (MS). An array of one or more deposition materials may be randomly deposited on a suitable surface, scanned with the SPM (or AFM) to take an initial reading of the topography of the deposition materials on the surface, and then exposed to a target sample containing a target material which may bind or interact to one or more of the deposition materials on the surface. The surface is then scanned again with the SPM to determine the molecular interaction sites and then these sites are analyzed using the MS to determine both the unknown and the deposition material.

Claims

1. A method for detecting a target material comprising:

depositing a deposition material on a surface;

exposing the deposition material to a target sample wherein the target sample contains one or more target materials that are to be characterized, the target material interacting with the deposition material on the surface to form a reaction product on the surface;

scanning the surface with a scanning probe microscope to locate the position of the reaction product on the surface;

desorbing the reaction product from the surface; and

detecting the desorbed reaction product.

2. The method of claim 1 further comprising analyzing an output from a mass spectrometer to characterize the reaction product desorbed from the surface.

3. The method of claim 1 wherein the reaction product is desorbed from the surface using a laser.

4. The method of claim 1 wherein the reaction product is desorbed from the surface using a probe attached to the scanning tunneling microscope.

5. The method of claim 1 wherein the scanning probe microscope is an atomic force microscope.

6. The method of claim 1 in which the scanning probe microscope is a near field optical microscope.

7. The method of claim 1 wherein the molecular interaction event includes one or more, of physisorption are hydrogen binding.

8. The method of claim 1 wherein the deposition the deposition material on the surface forms a deposition domain.

9. The method of claim 1 wherein the deposition material is an antibody.

10. The method of claim 1 wherein the deposition material is a protein.

11. The method of claim 1 wherein the target material is chosen from the group consisting of a protein, an antibody, a pathogen, and a virus.

12. The method of claim 1 wherein the surface includes a substrate.

13. The method of claim 12 wherein the substrate is chosen from one of the group consisting of glass, silicon, mica, and quartz.

14. The method of claim 1 wherein depositing the deposition material on the surface further comprises coating the surface with gold.

15. The method of claim 14 wherein depositing the deposition material on the surface further comprises attaching a C11-C18 alkane linker to the gold layer.

16. The method of claim 15 wherein the alkane linker includes a functional portion selected from a group consisting of a COOH, a NH2, and a succinimide.

17. The method of claim 15 wherein the alkane linker interacts with a primary amine of a protein.

18. The method of claim 1 wherein depositing the deposition material further comprises spraying the deposition material on the surface.

19. The method of claim 18 wherein the deposition material is a liquid.

20. The method of claim 18 wherein the deposition material is dissolved or suspended in a liquid.

21. The method of claim 18 wherein the material is sprayed as an aerosol spray.

22. The method of claim 1 wherein depositing the material on the surface further comprises:

crystallizing the deposition material;

depositing the crystallized deposition material on the surface;

hydrating the crystallized deposition material deposited on the surface.

23. The method of claim 22 wherein depositing the deposition material includes forming a deposition domain.

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

placing the surface at the bottom of a coating of liquid nitrogen;

freezing the deposition material in the liquid nitrogen and letting it fall to the surface;

removing the surface from the liquid nitrogen;

hydrating the deposition material.

25. The method of claim 24 wherein depositing the deposition material further comprises forming a deposition domain.

26. An apparatus for the detection and characterization of molecular interaction events comprising:

a scanning tunneling microscope; and

a mass spectrometer.

27. The apparatus of claim 26 wherein the mass spectrometer is operably integrated with the scanning tunneling microscope wherein the scanning tunneling microscope detects an interaction between a deposition material deposited on a surface and a target material and wherein at least the target material is desorbed from the surface and analyzed by the mass spectrometer.

28. A method for determining protein interactions

distributing randomly on a surface a first set of proteins;

imaging the randomly distributed proteins on the surface;

exposing the first set of proteins on the surface to a second set of proteins;

imaging the protein-protein interactions;

noting the location of the protein-protein interactions;

characterizing the protein-protein interactions using mass spectrometry.

29. The method of claim 28 wherein imaging is accomplished using a scanning probe microscope.

30. The method of claim 29 wherein the scanning probe microscope is an atomic force microscope.