Optical tweezers (OT) uses a focused laser beam to trap and move microscopic objects. The design of OT consists of laying out stationary and moving (or rotating) lenses and mirrors so that two design constraints are met at the objective back aperture (OBA): 1) the laser beam has to be pivoted around the center, and 2) the beam has to keep the same degree of overfilling. While these constraints are met, the objectives are to maximize the divergence/convergence angle and the beam rotation angle at the OBA. They are each accomplished by moving a lens or rotating a mirror, respectively. There are few known designs that give (claimed) good performances while satisfying above constraints. However, these designs are improvised inventions with no attempts in optimization. In this paper, we propose a new method for designing an optimized OT that achieves the best performance with given pool of optical elements. Our method, (Topology Optimization of the Optical Tweezers Setup) first divides the layout space into finite lattices and then distributes lenses and mirrors to appropriate lattices. Subsequently, whether the attempted configuration conforms to the constraints is tested. If the test is successful, the layout and its performance are recorded. At the end, the best performing layout is found. In this paper, we primarily concentrate on optimizing the positions of lens components. In the future, this approach will be generalized for more complicated configurations that include mirror components.© (2005) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.