(549b) Enhanced Performance of Entropic Trap Arrays Using End-Attached Micelles

Gel-free DNA separation methods are currently designed to either separate short DNA (typically 26 to 500 bp) with high (single-base) resolution or separate long DNA (typically 5000 bp to 48500 bp) with moderate (5000 bp) resolution. Here we present a computational investigation of integrating the rapid micelle electrokinetic chromatography technique known as micelle end-labeled free solution electrophoresis (Micelle ELFSE)¹ integrated into other microfabricated devices such as an entropic trap array²which should serve to synergistically increase separation performance and partially bridge this gap between short and long DNA separation performance.  

Micelle ELFSE utilizes end-attached non-ionic surfactant micelles that bring about a length dependent electrophoretic mobility on DNA oligomers in gel-free buffers. These micelles are tunable in size allowing one to optimize the separation performance of specific DNA target lengths. Additionally the separation device itself can be optimized with respect to geometry, such as channel dimensions and electric field strength. Entropic trap arrays are DNA separation devices that have repeating wide and narrow channel heights such that DNA is repetitively forced through a narrow constriction during electrophoresis. DNA oligomers of different lengths are separated as they cross an energy barrier upon entering confinement with a rate that depends on DNA size.  Micelle ELFSE and entropic trapping are compatible separation methods since long DNA elutes first in both cases.

Here, we demonstrate that use of end-attached micelles greatly improves the performance of entropic trap arrays.  Three relevant time scales were identified for DNA electrophoresis through an entropic trap that account for DNA approaching the narrow constriction, entering the constriction, and crossing the constriction³. We utilize Brownian dynamics simulations to investigate the sensitivity of each of these times scale to DNA tagged with a micelle. Simulations indicate a five-fold increase in resolution of the ELFSE-entropic device over simulations of the entropic trap alone.  We also discuss proper choice of micelle size and electric field for greatest enhancement.

1. J.M. Savard, S.T. Grosser, J.W. Schneider Electrophoresis 2008, 29, 2779-2789
2. J. Han, H. Craighead Science, 2000, 288, 1026-1029
3. A.J. Panwar, S. Kumar Macromolecules 2006, 39, 1279-1289