Simulation of electrophoretic stretching of DNA in a microcontraction using an obstacle array for conformational preconditioning

Abstract

Recently our group has reported experiments using an obstacle array to precondition the conformations of DNA molecules to facilitate their stretch in a microcontraction. Based upon previous successes simulating electrophoretic stretching in microcontractions without obstacles, we use our simulation model to study the deformation of DNA chains in a microcontraction preceded by an array of cylindrical obstacles. We compare our data to the experimental results and find good qualitative, and even quantitative, agreement concerning the behavior of the chains in the array; however, the simulations overpredict the mean stretch of the chains as they leave the contraction. We examine the amount of stretch gained between leaving the array and reaching the end of the contraction and speculate that the differences seen are caused by nonlinear electrokinetic effects that become important in the contraction due to a combination of field gradients and high field strengths.

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

“…A common approach to alleviate this problem is to "pre-condition" DNA so they adopt conformations more suitable for being stretched. Various conformation preconditioning strategies found in the literature include pre-shearing DNA, 19 passing DNA through a gel matrix 7 or obstacle arrays, 15,20 and exposing DNA to an oscillating extensional flow. 19 However, these methods are either troublesome to apply or having vary limited benefit.…”

“…Earlier simulations with the same assumptions yielded results in good agreement with the experimental data at small to moderate electric field (or Deborah number (De)). 20,23,26 With the help of computer simulations, we developed a new pre-conditioning approach called "pre-stretching." 1 The approach uses an expansion in front of the microcontraction to generate an electric field gradient to pre-stretch DNA.…”

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

“…In addition to the simulation results, the dotted line is given to indicate the maximum possible DNA extension. It is estimated using a dumbbell model at a homogeneous field (infinite strain), 43 and the result is independent of the molecular weight of DNA. From Fig.…”

“…46 Moreover, electric field gradient at the expansion and contraction of the proposed devices might induce dielectrophoresis effect that could polarize DNA and result in unpredictable influence to DNA behavior. 43,47 To summarize, in order to have an affordable but useful prediction, we use coarsed-grained models that hopefully preserve the most important physics but only leave away the unimportant ones. From the reasonable agreement between the previous experiments 28,33 and simulations, 26,48 the FEM-BD simulations used here should be capable to catch the behavior of the DNA in microfluidic devices.…”

Polymer stretch in two-phase microfluidics: Effect of wall wettability

“…5,6 Typical methods of stretching biopolymers include applying a force by a tweezers to an object attached to the free end of biopolymers or exerting a force to the biopolymers along its contour length by electric or hydrodynamic flow fields. [7][8][9] Those procedures are usually performed in single-phase flow system. Recently, it is further reported that biopolymers can also be stretched in two-phase flow microfluidics.…”