Simulation guided design of a microfluidic device for electrophoretic stretching of DNA

Abstract

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

Simulation of single DNA molecule stretching and immobilization in a de-wetting two-phase flow over micropillar-patterned surface

“…The integration of BD simulation with flow/electrical field computation has been carried out to study DNA dynamics in hydrodynamic and electrokinetic flows. 3,5,7,[29][30][31][32] However, previous studies only focused on 2-D and static/steady-state fields. In this study, we develop a BD-CFD simulation technique for DNA in complex transient physical systems.…”

Metropolis Integration Schemes for Self-Adjoint Diffusions

“…In the sequel, we use a BD model of DNA in a solvent to show that the new scheme achieves the same accuracy as explicit predictor-corrector schemes with time step sizes that are an order of magnitude (or more) larger. Beside BD, this scheme should also be useful in the simulation of polymer conformational transitions in electrophoretic flows [48,68,49,85,33,34], in other contexts where the effective dynamics of a set of coarse-grained variables satisfies (1.1) [10,59,58,11,53], in applications to Bayesian inference [15], etc.…”

Stretching DNA by electric field and flow field in microfluidic devices: An experimental validation to the devices designed with computer simulations

“…A more detailed discussion about the advantages and disadvantages of these preconditioning methods was given in our previous paper. 1 In our previous studies, 1,2 we have employed the Brownian dynamics simulations and finite element method 1,2,[21][22][23] to guide the design and the optimization of a microcontraction based DNA stretching microfluidic device. Our simulations were performed with the assumptions that DNA was driven electrophoretically through the device and any nonlinear electrokinetic phenomena 24,25 was neglected.…”

“…The same approximation has also been made in the previous studies. 1,2,7,23 In this study, the v outlet was determined experimentally by measuring DNA velocity in the device. However, since DNA moved very fast in the contraction, we instead measured the velocity of DNA at the wide part of the inlet channel (v widepart ) to infer v outlet .…”