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Design and optimization of backside-thinned CMOS active pixel sensors (APS) using modeling and simulation is presented. For the efficient design and the further improvement of our backside-thinned CMOS imagers, different models were developed and TCAD simulating tools were used. The imagers have been successfully designed, fabricated and tested and proved to possess excellent imaging properties. This short abstract paper presents a summary of the models and simulations covering two critical design and processing issues, namely the epilayer (EPI) structure and the pixel isolating trench formation process as well as their influence on the electrical inter-pixel crosstalk.