Force characterization and motion planning in automated cell manipulation by optical tweezers

Title: Force characterization and motion planning in automated cell manipulation by optical tweezers Authors: Wu, Yanhua ( 吳燕華) Abstract: Optical tweezers, which are based on the transfer of photon momentum, can trap and move microscale and nanoscale particles without physical contact. Rapid and precise transportation of live cells can benefit cell microsurgery, rare cell isolation, tissue engineering and cell-to-cell interactions. Increasing demands for both accuracy and efficiency in biological cell manipulation highlight the need for automation with robotics technology. Understanding the forces exerted on live cells is essential to biomechanical characterization and cell manipulation. However, traditional numerical force measurement assumes live cells to be ideal objects, ignoring their complicated inner structures and rough membranes. Furthermore, little reported research has specifically considered the synergy of dynamic analysis in motion planning during automated transportation. The problem of planning cell motion with optimized motion parameters, using cell dynamics analysis, is still very challenging. This thesis aims to characterize the mechanical forces applied to live cells in optical traps, and use the mechanical parameters thus obtained to plan cell motion during automated transportation. The research principally consists of the following three elements. First, the forces applied to live cells are calibrated by a novel static viscous-drag-force method. Unlike existing approaches, the proposed method does not assume the live cells to share the same optical and/or drag parameters as those of polystyrene/silica beads. By binding a micro polystyrene sphere to the live cell and moving the mixture with optical tweezers, the drag force on the cell can be obtained by subtracting the drag force on the sphere from the total drag force on the mixture, under the condition of an extremely low Reynolds number. The trapping force on the cell is then obtained from the drag force when the cell is in the force equilibrium state. Second, motion planning strategy, which is designed using dynamics analysis of the optically trapped cell, is used to determine the ideal movement velocity of the cell. Due to property changes in the aqueous medium and laser during cell transportation, the calibrated dynamic parameters may vary, and thus, the cell movement velocity designed using these parameters should be adjusted online. A proportional-integral (PI) scheme is used to adjust the cell movement velocity online, to ensure that the cell moves at an ideal speed and does not escape from the laser focus. Dynamics analysis results are used to design the PI scheme. Third, an optimal path for cell movement is planned, using a modified A-star algorithm, which introduces an additional cost to penalize waypoints where the direction of movement changes. The algorithm balances smoothness and movement cost. Finally, experiments on moving yeast cells are conducted to demonstrate the effectiveness of the proposed approach. The main contribution of this study lies in the development of a new experimental method to characterize the mechanical forces exerted on live cells, and the application of the dynamic analysis results to motion planning for automated cell transportation. Notes: CityU Call Number: TK8360.O69 W8 2011; ix, 95 leaves : ill. 30 cm.; Thesis (Ph.D.)--City University of Hong Kong, 2011.; Includes bibliographical references (leaves 84-94)