Atomic force microscope for biological specimens

• US 5,874,668 A
• Filed: 10/24/1995
• Issued: 02/23/1999
• Est. Priority Date: 10/24/1995
• Status: Expired due to Fees

• Current Assignee: ARCH Development Corporation (University of Chicago)
• Original Assignee: ARCH Development Corporation (University of Chicago)
• Inventors: Xu, Shaohua, Arnsdorf, Morton F.
• Primary Examiner(s): Williams, Hezron E.
• Assistant Examiner(s): LARKIN, DANIEL SEAN
• Application Number:
  US08/547,521
• Time in Patent Office: 1,218 Days
• Field of Search: 73/105, 250/306
• US Class Current: 73/105
• CPC Class Codes: B82Y 35/00 Methods or apparatus for measurement or analysis of nanostructures
• CPC Class Codes: G01Q 60/42 Functionalisation
• CPC Class Codes: Y10S 977/853 Biological sample

Abstract

An atomic force microscope for quantitative imaging and identification, at the molecular or submolecular level, biomolecules or subunits of biomolecules in a physiologic environment, through use of a cantilever tip incorporating a biomolecular identifier.

Claims

1. An atomic force microscope for probing a biological specimen, comprising:

a cantilever arm having a cantilever tip attached thereto, said cantilever tip including means for identifying biomolecules on the surface of said biological specimen with said means comprising an amphipathic molecule coupled to said cantilever tip for interaction with a biological site of interest;

means for providing a laser beam for reflecting off said cantilever tip;

means for scanning said cantilever tip relative to said biological specimen; and

means for detecting said reflected laser beam.

2. The atomic force microscope as defined in claim 1 wherein said amphipathic molecule is selected from the group consisting of small lipid molecules, detergents, and large macromolecules.

3. The atomic force microscope as defined in claim 2 wherein said amphipathic molecules are selected from the group consisting of charged molecules and zwitterions.

4. The atomic force microscope as defined in claim 1 wherein said cantilever tip comprises at least one leg portion and at least one of a hole and a cutout in said leg portion.

5. The cantilever tip as defined in claim 4 wherein said leg portion includes a plurality of holes.

6. The cantilever tip as defined in claim 5 wherein said cantilever tip comprises at least two of said leg portions.

7. The cantilever tip as defined in claim 6 wherein said leg portions have different patterns of said holes.

8. The atomic force microscope as defined in claim 1 wherein said tip comprises a ceramic material.

9. The atomic force microscope as defined in claim 1 wherein said amphipathic molecule has a pKa near a pH to be measured.

10. An atomic force microscope for probing a biological specimen, comprising:

a cantilever arm having a cantilever tip attached thereto, said cantilever tip including means for identifying biomolecules on the surface of said biological specimen wherein said means for identifying biomolecules comprises at least one of receptor molecules coated onto said cantilever tip, a zwitterion liquid coating, amphipathic liquids having protein donors, amphipathic liquids having protein acceptors, and hydrophobic molecules;

means for providing a laser beam for reflecting off said cantilever tip;

means for scanning said cantilever tip relative to said biological specimen; and

means for detecting said reflected laser beam.

11. An atomic force microscope for probing a biological specimen, comprising:

a cantilever arm having a cantilever tip attached thereto wherein said cantilever tip is coated with photoactivated charges, said cantilever tip including means for identifying biomolecules on the surface of said biological specimen;

means for providing a laser beam for reflecting off said cantilever tip;

means for scanning said cantilever tip relative to said biological specimen; and

means for detecting said reflected laser beam.