R21: DNA Electrophoresis on nanostructured surfaces

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DESCRIPTION (provided by applicant): We propose to develop a novel methodology to separate DNA and related biomolecules using nanostructured surfaces. We will use a combination of theoretical and experimental methods to study electrophoresis of charged biological molecules on patterned surfaces. The goal is to understand the fundamental mechanisms which control the dynamics near surfaces and to formulate predictive models which will allow the engineering of high resolution separation devices with optimum throughput and chemical selectivity. Nanoscale patterns will be imprinted using polymer self assembly, while more complicated micron scale structures with a combination of topological and chemical patterns will be manufactured by micro-contact printing. Electrophoresis will be performed and the mobility of DNA chains on these various surfaces will be observed either by confocal, near field microscopy, or CCD coupled video imaging. Fluorescence recovery after photobleaching (FRAP) coupled with Linear Dichroism detection (FDLD) will be used to measure surface relaxation times and diffusivity. The measurements will be performed as a function of pattern morphology, buffer concentration, chemical interactions, and chain structure. From these measurements we should be able to elucidate the relative importance of surface interactions, surface charges, electroosmotioc flow, and topological confinement in the surface dynamics of charged molecules. Due to the complexity of the problem, a variety of complementary theoretical treatments will be employed in order to obtain a quantitative model. Coarse grained models will be used to focus the application of more computationally intensive molecular models into those regions of phase space which control the behavior of the system. Theoretical methods used will range from Molecular dynamics simulations, to scaling analysis, to studies of flow on patterned media. The results should have broad applicability to a variety of devices and molecules including microfluidic channels, microarrays, complexed proteins, and cellular materials.