DNA Polymer Dynamics in Nanoconfinement

纳米限制中的 DNA 聚合物动力学

• 批准号: 0852235
• 负责人: Patrick Doyle
• 金额: --
• 依托单位: Massachusetts Institute of Technology
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0852235&HistoricalAwards=false
• 关键词: DNA; Polymer; Dynamics; Nanoconfinement

CBET - 0852235 Doyle, Patrick S. This project studies the equilibrium and non-equilibrium dynamics of double stranded DNA in nanofluidic devices. The project will combine state-of-the-art nanofabrication, single molecule imaging and molecular modeling. The fundamental goal is to understand molecular transport in highly confined geometries with application to single molecule DNA mapping. The project has four primary objectives. 1) Measure transport coefficients and size of highly confined DNA. 2) Design and fabricate cross-slot devices to study electrophoretic stretching and relaxation of confined DNA. 3) Develop single molecule DNA mapping methods with stretching in cross-slot devices. 4) Develop scaling theories, Brownian dynamics simulations and other models to support the experimental studies. Confined DNA in nano-slits with heights smaller than the DNA's bulk radius of gyration is a relatively unexplored regime. DNA size and transport coefficients (diffusion coefficient, longest relaxation time, electrophoretic mobility) should be extremely sensitive to the local environment. The PI will construct experimental systems to study highly confined DNA with slit heights as small as 10nm. The PI will also build devices to electrophoretically stretch DNA in nanoslit cross-slot devices. Initial results point to the possibility of a new "2-step" coil-to-stretch transition that will be explored in detail both experimentally and theoretically. These nanoslit devices will not only allow for many fundamental polymer physics studies, but be excellent platforms for mapping single DNA molecules. To this end, the PI will develop means to selectively tag DNA at specific sites with quantum dots and then read off this barcoded molecule using the cross-slots. Simulations and scaling theories will lend support to the experiments. The single DNA mapping has clear impact on disease diagnostics, pathogen detection and drug discovery. The PI will engage undergraduate educators and students from other universities through the Research Experience for Teachers and Research Experience for Undergraduates programs and develop microfluidic modules they can take back to their universities. Videos for K-12 teachers will be developed for the Teacher's Domain repository maintained by Boston public radio. Web-based and short-course tutorials will be developed on topics of single molecule experiments and nano-scale transport.

Doyle，帕特里克S. 本计画研究奈米流体装置中双股DNA的平衡与非平衡动力学。该项目将结合联合收割机国家的最先进的纳米织物，单分子成像和分子建模。基本目标是了解分子在高度受限的几何形状中的输运，并将其应用于单分子DNA作图。该项目有四个主要目标。1)测量高度受限的DNA的传输系数和大小。2)设计并制作交叉狭缝装置，以研究受限DNA的电泳拉伸与松弛。3)开发在交叉槽装置中拉伸的单分子DNA作图方法。4)发展标度理论，布朗动力学模拟和其他模型来支持实验研究。 在高度小于DNA的体积回转半径的纳米狭缝中的受限DNA是相对未探索的区域。DNA的大小和传输系数（扩散系数，最长弛豫时间，电泳迁移率）应该对局部环境非常敏感。 PI将构建实验系统来研究高度受限的DNA，狭缝高度小至10 nm。PI还将构建在纳米缝交叉槽设备中对DNA进行弹性拉伸的设备。初步结果指出，一个新的“2步”线圈拉伸过渡，将在实验和理论上详细探讨的可能性。这些纳米缝装置不仅可以进行许多基础的聚合物物理研究，而且是绘制单个DNA分子的绝佳平台。为此，PI将开发在特定位点用量子点选择性标记DNA的方法，然后使用交叉槽读取这种条形码分子。模拟和缩放理论将为实验提供支持。单DNA图谱对疾病诊断、病原体检测和药物发现具有明显的影响。PI将通过教师研究经验和本科生研究经验项目吸引其他大学的本科教育工作者和学生，并开发他们可以带回大学的微流体模块。将为波士顿公共广播电台维护的教师领域库开发K-12教师视频。将就单分子实验和纳米尺度传输的主题开发基于网络的短期教程。