Abstract

Actual forces and dimensions in DNA cells are very small and, in some cases, they are less than can be measured by regular atomic force microscopes operating in the static regime, or even at the natural vibration of nanocantilevers. In nucleic acid studies, the interesting range of forces begins at the sub-piconewton. A cantilever with higher mode oscillation allows us to increase AFM sensitivity and resolution up to atomic level with femtometer (fm = 10−15 m) and zeptogram (zg = 10−21 g) scales. Note that sensitive fluorescence microscopy has resolution only of 2 × 10−7 m (2 × 10−1 μm). In this chapter, we study force and mass resolution of AFM at higher oscillation modes, and demonstrate an increase of AFM sensitivity up to a hundred times in the fourth oscillation mode. Such sensitive measuring systems can be challenging to use, specifically calibrating them and isolating them from the influence of surrounding environmental factors (temperature, noise, vibration, etc.). Their effective calibration and protection against influence factors is also considered in this chapter.

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