Direct visualization of unstained nucleic acids on a metal substrate

Unstained DNA has been directly imaged for the first time on a metallic substrate. Reproducible, three-dimensional images of molecular morphology following aqueous deposition onto tungsten have been obtained. The images confirm the importance of reducing surface tension forces during drying. Preadsorption of poly-l-lysine seems to improve image quality although optimum conditions are quite different than those reported in the TEM literature for insulating substrates. Our results suggest that poly-l-lysine should be preadsorbed as a neutral molecule at high pH. Following adsorption, the pH should be reduced in order to establish a net positive surface charge density. The presence of positive charges on a tungsten surface helps to preserve DNA morphology following adsorption from aqueous solution.