Modelling of electrokinetic phenomena involving confined polymers: Applications to DNA separation and electroosmotic flow control

Abstract

Microfluidic and nanofluidic technology is revolutionizing experimental practices in analytical chemistry, molecular biology and medicine. Indeed, the development of systems of small dimensions for the processing of fluids heralds the miniaturization of traditional, cumbersome laboratory equipment onto robust, portable and efficient microchip devices (similar to the electronic microchips found in computers). Moreover, the conjunction of scale between the smallest man-made device and the largest macromolecules evolved by Nature is fertile ground for the blooming of our knowledge about the key processes of life. In fact, the conjunction is threefold, because modern computational resources also allow us to contemplate a rather explicit modelling of physical systems between the nanoscale and the microscale. In the five articles comprising this thesis, we present the results of computer simulations that address specific questions concerning the operation of two different model systems relevant to the development of small-scale fluidic devices for the manipulation and analysis of biomolecules. First, we use a Bond-Fluctuation Monte Carlo approach to study the electrophoretic drift of macromolecules across an entropic trap array built for the length separation of long, double-stranded DNA molecules. We show that the motion of the molecules is consistent with a simple balance between electric and entropic forces, in terms of a single characteristic parameter. We also extract detailed information on polymer deformation during migration, predict the separation of topoisomers, and investigate innovative ratchet driving regimes. Secondly, we present theoretical derivations, numerical calculations and Molecular Dynamics simulation results for an electrolyte confined in a capillary of nanoscopic dimensions. In particular, we study the effectiveness of neutral grafted polymer chains in reducing the magnitude of electroosmotic flow (fluid flow induced by an external electric field). Our results constitute the first independent, quantitative verification of theoretical scaling predictions for the coupling between grafted macromolecules and electroosmotic flow. Such simulations will contribute to the rationalization of the existing empirical knowledge about flow control with polymer coatings.