Statistical Mechanics and Computer Simulations with Applications in Micro- and Nano-Fluidics and Biological Physics

在过去的10-15年里，我们见证了实验科学和计算科学的显著融合。事实上，虽然实验学家现在可以研究DNA或蛋白质等单一分子，甚至可以建立由极少数分子组成的纳米系统(例如纳米通道)，但理论家现在拥有理论和计算工具，可以逐个分子地研究完全相同的系统。巨大的计算机使制作分子电影和详细预测成为可能。这种融合在包括生物物理学和分离科学在内的许多学科中开启了令人难以置信的可能性。在这项拨款申请中，我们建议研究软物质物理、分析化学、生物技术、计算科学和生物物理之间的几个问题：**(1)我们将使用分子级别的计算机模拟来研究用于分离和分析DNA和蛋白质的微和纳米流体系统(在介质中通常被称为芯片上实验室系统)。**(2)我们将继续开发我们的革命性的扩散和漂移晶格模型。我们将把我们的工作扩展到具有高电场和脉冲电场的生物分子的分离、棘轮系统、腔体网络、药物输送系统(例如，凝胶为基础的药丸)、复杂的几何结构...**(3)我们将继续研究和开发新的微流控技术。特别是，我们将研究长DNA分子的分离，使用人工介质作为脆弱凝胶的替代品，以及基于热力学棘轮系统的设备的设计。**(4)我们将对DNA通过狭窄毛孔的过程进行建模，这一过程很可能是下一代DNA测序仪背后的过程。我们将研究噪声的作用，脉冲电场的利用，最后是发生在活细胞中的这个过程的一些生物学方面。**(5)最后，我们将对不对称设备中游动细菌的集体运动进行建模，看看这些设备是否可以根据细胞的生物物理特性来分离细胞。

Over the last 10-15 years, we have witnessed a remarkable convergence of the experimental and computational sciences. Indeed, while experimentalists can now study single molecules such as DNA or proteins, or even build nanoscopic systems (e.g., nanochannels) made of a very small number of molecules, theoreticians now possess the theoretical and computational tools to study the very same systems, molecule by molecule. Massive computers make it possible to make molecular movies and detailed predictions. This convergence opens incredible possibilities in a number of disciplines, including biophysics and the separation sciences. In this grant application, we propose to investigate several problems at the interfaces between soft matter physics, analytical chemistry, biotechnology, computational science, and biophysics:**(1) We will use molecular-level computer simulations to study micro- and nanofluidic systems used to separate and analyze DNA and proteins (what is often called lab-on-a-chip systems in the media).**(2) We will continue the development of our revolutionary lattice model of diffusion and drift. We will extend our work to study the separation of biomolecules with high and pulsed electric fields, ratchet systems, networks of cavities, drug-delivery systems (e.g., gel-based pills), complex geometries, ...**(3) We will continue the study and development of new microfluidic technologies. In particular, we will examine the separation of long DNA molecules, the use of artificial media as a substitute to fragile gels, and the design of devices based on thermodynamic ratchet systems.**(4) We will model the passage of DNA through narrow pores, the process that will most likely be behind the next generation of DNA sequencers. We will examine the role of noise, the utilization of pulsed electric fields, and finally some biological aspects of this process as it occurs in live cells.**(5) Finally, we will model the collective motion of swimming bacteria in asymmetric devices to see if these devices can be used to separate the cells according to their biophysical properties.********************