Optimizing single DNA molecules manipulation by AFM

Recent progress in single DNA manipulation with atomic force microscope has proved its potential in analysing genetic information at the molecular level instead of macro ensemble approach. However, current manipulation of DNA is mainly carried out by manual operations, which is labour-intensive and time-consuming, thus limits the further applications in other fields. In this paper, an optimized DNA manipulation method is successfully established. An image correlation technique is introduced to realize automatic thermal drift compensation. Combined with elaborately designed tip movement control for different manipulation purposes, accurate and efficient DNA manipulations such as dissection, folding and picking are realized. The efficiency has been improved for an order of magnitude compare to manual manipulations, whereas the performance is demonstrated to be the same. This newly developed method has shed light on high-efficiency nanomanipulation of small molecules with complex structures, and thus provides the possibility of deeply understanding the intrinsic properties of single biomolecules.