AFM-tip functionalization for single molecule recognition imaging

The high force sensitivity of the atomic force microscope (AFM) has opened the possibility of measuring inter- and intramolecular forces of biomolecules on the single molecule level. Covalent binding of bioligands to AFM tips converts them into monomolecular biosensors by which cognate receptors can be localized on the sample surface and fine details of ligand-receptor interaction can be studied. Tethering of the bioligand to the AFM tip via a ∼6 nm long, flexible poly(ethylene glycol) linker (PEG) allows the bioligand to freely reorient and to rapidly 'scan' a large surface area while the tip is at or near the sample surface. Using suchlike modified AFM tips, a recent technology development lead to molecular recognition imaging, where topography and recognition sites are simultaneously localized with nanometer accuracy. Thus, the AFM can identify specific components on complex biological sample and retain its high resolution in imaging.