We have used Brownian dynamics-finite element method (BD-FEM) to guide the optimization of a microfluidic device designed to stretch DNA for gene mapping. The original design was proposed in our previous study [C. C. Hsieh and T. H. Lin, Biomicrofluidics 5(4), 044106 (2011)] for demonstrating a new pre-conditioning strategy to facilitate DNA stretching through a microcontraction using electrophoresis. In this study, we examine the efficiency of the original device for stretching DNA with different sizes ranging from 48.5 kbp (k-DNA) to 166 kbp (T4-DNA). The efficiency of the device is found to deteriorate with increasing DNA molecular weight. The cause of the efficiency loss is determined by BD-FEM, and a modified design is proposed by drawing an analogy between an electric field and a potential flow. The modified device does not only regain the efficiency for stretching large DNA but also outperforms the original device for stretching small DNA. V C 2012 American Institute of Physics. [http://dx

Recently, we have reported the experimental results of DNA stretching by flow field in three microchannels (C. H. Lee and C. C. Hsieh, Biomicrofluidics 7(1), 014109 (2013)) designed specifically for the purpose of preconditioning DNA conformation for easier stretching. The experimental results do not only demonstrate the superiority of the new devices but also provides detailed observation of DNA behavior in complex flow field that was not available before. In this study, we use Brownian dynamics-finite element method (BD-FEM) to simulate DNA behavior in these microchannels, and compare the results against the experiments. Although the hydrodynamic interaction (HI) between DNA segments and between DNA and the device boundaries was not included in the simulations, the simulation results are in fairly good agreement with the experimental data from either the aspect of the single molecule behavior or from the aspect of ensemble averaged properties. The discrepancy between the simulation and the experimental results can be explained by the neglect of HI effect in the simulations. Considering the huge savings on the computational cost from neglecting HI, we conclude that BD-FEM can be used as an efficient and economic designing tool for developing new microfluidic device for DNA manipulation.