Computational Studies of DNA Separations in Micro-Fabricated Devices: Review of General Approaches and Recent Applications

DNA separation techniques have drawn attention because of their uses in applications such as gene analysis and manipulation. There have been many studies utilizing micro-fabricated devices for faster and more efficient separations than traditional methods using gel electrophoresis. Although many experimental studies have presented various new devices and methods, computational studies have played a pivotal role in this development by identifying separation mechanisms and by finding optimal designs for efficient separation conditions. The simulation of DNA separation methods in micro-fabricated devices requires the correct capture of the dynamics and the structure of a single polymer molecule that is being affected by an applied flow field or an electric field in complex geometries. In this work, we summarize the polymer models (the bead-spring model, the bead-rod model, the slender-body model, and the touching-bead model) and the methods, focusing on Brownian dynamics simulation, used to calculate inhomogeneous fields taking into consideration complex boundaries (the finite element method, the boundary element method, the lattice-Boltzmann method, and the dissipative particle dynamics simulation). The worm-like chain model (adapted from the bead-spring model) combined with the finite element method has been most commonly used but other models have shown more efficient and accurate results. We also review the applications of these simulation approaches in various separation methods and devices: gel electrophoresis, post arrays, capillary electrophoresis, microchannel flows, entropic traps, nanopores, and rotational flows. As more complicated geometries are involved in new devices, more rigorous models (such as incorporating the hydrodynamic interactions of DNA with solid boundaries) that can correctly capture the dynamic behaviors of DNA in such devices are needed.