High-Yield Characterization of Single Molecule Interactions with DeepTip(TM) Atomic Force Microscopy Probes

Single molecule interactions between biotin and streptavidin were characterized with functionalized DeepTip(TM) probes and used as a model system to develop a comprehensive methodology for the high-yield identification and analysis of single molecular events. The procedure comprises the covalent binding of the target molecule to a surface and of the sensing molecule to the DeepTip(TM) probe, so that the interaction between both chemical species can be characterized by obtaining force–displacement curves in an atomic force microscope. It is shown that molecular resolution is consistently attained with a percentage of successful events higher than 90% of the total number of recorded curves, and a very low level of unspecific interactions. The combination of both features is a clear indication of the robustness and versatility of the proposed methodology.