Methods for imaging DNA in liquid with lateral molecular-force microscopy.

Shear force microscopy is not normally associated with the imaging of biomolecules in a liquid environment. Here we show that the recently developed scattered evanescent wave (SEW) detection system, combined with custom-designed vertically oriented cantilevers (VOCs), can reliably produce true non-contact images in liquid of DNA molecules. The range of cantilever spring constants for successful shear force imaging was experimentally identified between 0.05 and 0.09 N m(-1). Images of lambda-DNA adsorbed on mica in distilled water were obtained at scan rates of 8000 pixels s(-1). A new constant-height force mapping mode for VOCs is also presented. This method is shown to control the vertical position of the tip in the sample plane with better than 1 nm accuracy. The force mode is demonstrated by mapping the shear force above lambda-DNA molecules adsorbed on mica in a liquid environment at different tip-sample separations.