| The thesis focuses on improving the efficiency and precision of nano-manipulation, especially single DNA manipulation, with Atomic Force Microscope (AFM). A high efficiency nano-manipulation system has been realized, and an intelligent manipulation strategy has been developed. For the explanation of experimental results, models of DNA manipulation processes have also been developed, and the manipulation mechanics therein have been discussed.Nano-manipulation technique was introduced with the development of Scanning Probe Microscopy (SPM) in 1980s. It enables'true'single atoms/molecules research for the first time, and shows great potential in the fields of semi-conductors, materials, chemistry, medical etc. Among the SPM family, the AFM has become the most popular tool for single molecule manipulation applications, as there are almost no limitation for samples and environment conditions. For example, in bio-medical researches, traditional biochemical analysis is based on statistic information of large amount of molecules, losing the"spacial resolution". The atomic force microscope could observe and manipulate directly single molecules and their interactions, thus essential for revealing important life secrets and accelerate next-generation"personalized medical care". Such as the mechanical properties of DNA folding structures could be studied by nano stretching, and mechanical interaction induced mutation could be systematically analyzed.However, current efficiency of AFM manipulation is not satisfactory, mainly because of the following reasons:(1) The AFM tip is not only for imaging but also for manipulation. Therefore, during manipulation, one has to frequently switch between imaging mode and manipulation mode, costing a lot of time and operations. Besides, the AFM scanning is inherently slow due to the raster scanning pattern.(2) There are thermal drifts. Thermal drift is the small deformation of instruments due to thermal fluctuations. It is not obvious in the macro world, however, it matters in the nano scale, and must be compensated during manipulation for high precision.(3) The tip-sample interactions during manipulation are complicated. There are van der Waals force, capillary force, electrostatic forces, chemistry force etc., making the understanding of manipulation process very difficult.To address above issues, the main topics of the thesis includes the following aspects:(1) To improve manipulation efficiency. Designed high efficiency tip movements according to different manipulation purposes. Simplified the manipulation processes by eliminating mode switching through localized manipulation.(2) To improve manipulation precision. Developed a thermal drift compensation method based on image registration. Realized sub-pixel compensation precision by introducing Least Square Estimation and Kalman Filter Estimaiton. Besides, this compensation method could also be used to calibrate AFM image distortion caused by thermal drift during scanning.(3) To further improve the efficiency. Developed an image recognition algorithm for low signal-to-noise ratio AFM images, e.g. DNA image, and successfully applied in nano-manipulation, providing an automatic and intelligent manipulation stragetgy.(4) Developed models of DNA manipulation processes. Discussed important factors in nano-manipulation.Though the nano-manipulation with AFM has demonstrated great potential, there are few studies on improving the manipulation efficiency, especially for biomolecule manipulations. The developed methods and models in the thesis could shed some lights for high efficiency AFM manipulation, thus facilitating the application of this single molecule manipulation strategy. Keywords: Atomic Force Microscopy, DNA, Nano-manipulation, Automatization...
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