(586h) Monte Carlo Simulations of DNA Electrophoresis Via Entropic Trapping Transport through Polydisperse Nanoscale Pores

Microscale transport of biomolecules through nanoporous surroundings is critical in applications such as electrokinetic DNA and protein separations. The selectivity of these separation processes is governed by the physical transport mechanism by which the macromolecular analytes navigate through the pore network and the rate at which their mobility and dispersion scale with their molecular size. Previous studies have shown how a time-varying electric field driving force enables entropic trapping-dominated transport of DNA through heterogeneous hydrogel networks via an activated process of hops between larger-sized pores joined by narrow connecting spaces. However, although entropic trapping can deliver improved size-selective resolving power compared with conventional constant-field reptation-based approaches, predictive transport models can only capture experimentally measured mobility over a limited analyte size range. Additionally, separations of double-stranded DNA below 500 base pairs in length have not been widely considered despite their importance in any diagnostic and analytical applications. Here, we present progress toward addressing these shortcomings. First, we introduce a transport model that overcomes the limitations of prior approaches where DNA mobility was described using a simple function of the macromolecule’s radius of gyration and the applied electric field. Our improved model incorporates a more detailed evaluation of the single-file DNA migration time through narrow space (constriction region) connecting neighboring larger pores. Second, we apply an activation time model for entry into the constriction that replaces the previously assumed reptation-based dynamics with a framework that more accurately captures the conformation of short double-stranded DNA. When these refinements are applied to calculate electrophoretic DNA mobility, we obtain results in close agreement with experimental measurements over a much broader range of DNA size and nanoporous network polydispersity than previously demonstrated. These insights suggest new opportunities to design electrophoretic separation systems that maximize the selectivity of macromolecular analytes.