Patent ID: 7989164

Claim:
A method for distinguishing complexed from non-complexed macromolecules in a sample disposed on discrete locations on a substrate, the method comprising the steps of: (a) vibrating a coupled torsional harmonic cantilever with a sharp offset tip that interacts with a surface of a sample at or near a flexural resonance frequency and obtaining a torsional deflection signal representing one or more harmonics of said flexural resonance frequency from said vibrating; (b) contacting the vibrating coupled torsional harmonic cantilever with a sharp tip with a sample comprising complexed and non-complexed macromolecules, said macromolecules disposed at discrete locations on said substrate, wherein a discrete location may contain a complexed macromolecule or a non-complexed macromolecule, and wherein the contacting is conducted in air; (c) measuring changes in said torsional deflection signal at different discrete locations depending on whether a macromolecule at said different discrete locations is complexed or non-complexed and; (d) measuring changes in tip-sample forces through said changes in said torsional deflection signal, wherein said changes in tip-sample forces result from changes in mechanical properties caused by complexing of the macromolecules on the substrate, thereby distinguishing said complexed macromolecules from said non-complexed macromolecules.