Improved Kelvin probe force microscopy for imaging individual DNA molecules on insulating surfaces

Electrostatic forces and potentials are keys in determining the interactions between biomolecules. We have recently imaged the topography and electrostatic surface potential of nucleic acid molecules on silicon surfaces using Kelvin probe force microscopy (KPFM). Here, we demonstrate KPFM imaging on insulating surfaces like mica, which provides access to configurations of DNA that are projections of its structure in solution. In particular, we apply dual-frequency mode to minimize the tip-sample distance at which the Kelvin probe signal is acquired and use the fundamental resonance of the cantilever to determine surface potential and its first overtone to detect the topography.