Quantitative manipulation of DNA and viruses with the nanoManipulator scanning force microscope

The nanoManipulator, a modified scanning force microscope with a direct man ipulation interface that allows natural and controlled manipulation of nano meter-sized samples, was used to investigate DNA and adenoviruses, During a manipulation, the scanning tip is coupled to a hand-held stylus via a forc e-feedback loop, Accordingly, the tip follows the movement of the user's ha nd; moreover, the user is able to feel the topography of the sample, For im aging fragile biological samples, a magnetically driven intermittent contac t (MDIC) mode in fluid was implemented and added to the microscope. In this mode, a cantilever with a magnetic particle glued onto its back is driven by an external, oscillating magnetic field. In contrast to regular intermit tent contact (tapping) mode imaging in liquids, where the whole liquid cell . is excited (resulting in many resonance peaks in the spectrum), in this m ode the cantilever is driven directly and the spectrum usually displays a s ingle, easily identifiable resonance peak, Using this set-up, adenoviruses were manipulated in liquids and 1100 bp DNA molecules were manipulated in a mbient conditions while recording lateral force data. In these experiments, the rupture force of DNA was measured directly for the first time. In an e ffort to measure the interaction force between a virus and a substrate, ade noviruses were pushed over a silicon substrate. A force of similar to 25 nN was measured to move the virus on this surface. Copyright (C) 1999 John Wi ley & Sons, Ltd.