DNA Electrophoresis on nanostructured surfaces

描述(由申请人提供)：我们建议开发一种使用纳米结构表面分离DNA和相关生物分子的新方法。我们将使用理论和实验相结合的方法来研究带电生物分子在图案化表面上的电泳。其目的是了解控制表面附近动力学的基本机制，并建立预测模型，使高分辨率分离设备的设计具有最佳的生产能力和化学选择性。纳米级的图案将通过聚合物自组装来压印，而更复杂的微米级结构将通过微接触打印来制造，这些结构结合了拓扑和化学图案。将进行电泳，并将通过共聚焦、近场显微镜或CCD耦合视频成像来观察DNA链在这些不同表面上的移动。光漂白后的荧光恢复(FRAP)和线性二向色性检测(FDLD)将被用来测量表面弛豫时间和扩散系数。测量将作为图案形态、缓冲液浓度、化学相互作用和链结构的函数来执行。通过这些测量，我们应该能够阐明表面相互作用、表面电荷、电动势流和拓扑限制在带电分子表面动力学中的相对重要性。 由于问题的复杂性，将采用多种互补的理论处理，以获得定量的模型。粗粒度模型将被用来将计算更密集的分子模型的应用集中到控制系统行为的相空间区域。使用的理论方法将从分子动力学模拟，到标度分析，再到对图案化介质上流动的研究。这些结果应该广泛适用于各种设备和分子，包括微流控通道、微阵列、复杂蛋白质和细胞材料。

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.