Molecular Sieving in Two-Dimensional Periodic Free-Energy Landscapes Created by Patterned Nanofluidic Devices

Pi：Fu，建平研究所：密歇根大学-安娜堡分校学术价值：高效纳米流体筛分结构的开发代表着朝着优化生物分离方法并将其集成到完全集成的生物分析微系统上迈出的重要一步。鉴于目前纳米流体蛋白质组学的研究重点，了解受限纳米流体筛选环境中的分子传输特性变得至关重要。因此，这项研究的主要目标是从实验和理论上研究限制纳米流体环境的分子动力学，以及如何利用这些知识来设计用于先进生物分离的新型纳米流体筛分结构。不同的微米和纳米制造方法将被用来产生亚100 nm的纳米流体筛分结构。我们将仔细研究这些纳米流体结构的不同结构参数和外加电场对它们的分离性能(如尺寸选择性和分离分辨率)的影响。实验结果将用于指导动力学模型的开发和进一步验证。反过来，理论建模的预测将被用于激励新的分离分析，并指导改进的设计和纳米流体筛分结构的生成。实验和理论建模之间的双向验证过程将导致对受限纳米流体几何中的分子动力学的严格理解。间接影响：由于其跨学科性质，拟议的研究将无缝集成不同领域的知识，包括微/纳米制造、微/纳米流体、受阻传输、聚合物物理和单分子的荧光成像。这项拟议的研究如果成功，将促进使用合成纳米流体结构分离与生理相关的分子的变革性进展，这是朝着实现纳米流体蛋白质组研究和未来高度集成的生物分析微/纳米系统的承诺迈出的关键一步。这项研究还将导致对受限纳米流体几何结构中分子动力学的深入了解，这可能为超灵敏和高分辨率传感器和医疗诊断系统提供新的基础。拟议的教育活动将对不同教育水平、性别和种族的学生产生广泛影响。提案中描述的一些技术将被用作向安娜堡和伊普西兰蒂学区的K-12学生以及其他代表性不足的女性和少数族裔学生开展外联活动的工具。拟议的外展活动将向K-12学生揭示科学和工程领域令人兴奋的挑战及其与我们社会的密切联系，从而激励他们学习科学和工程课程。对于本科和研究生教育，将开发一门微米/纳米流体学和生物微机械的跨学科课程。本课程将为工程学学生在生物微机械和芯片实验室、分析化学和微/纳米材料科学等多学科领域的研究做好准备。

PI: Fu, JianpingInstitution: University of Michigan - Ann Arbor Intellectual Merit: Development of efficient nanofluidic sieving structures represents a major step toward optimizing bioseparation methods and integrating them onto a fully integrated bioanalysis microsystem. In light of the current research thrust of nanofluidic proteomics, it becomes critically important to understand molecular transport properties in constraining nanofluidic sieving environments. Thus, the major goal of this research is to study, both experimentally and theoretically, molecular dynamics in confining nanofluidic environments and how such knowledge can be utilized to design novel nanofluidic sieving structures for advanced bioseparation. Different micro- and nano-fabrication methods will be applied to generate sub-100 nm nanofluidic sieving structures. These nanofluidic structures will be carefully examined to investigate how their separation performances (such as size selectivity and separation resolution) are affected by different structural parameters of the nanofluidic structures and the external electric fields. Experimental results will be used to guide developments of kinetic models and further validate them. Reciprocally, predictions from theoretical modeling will be used to motivate new separation assays and guide improved designs and generations of the nanofluidic sieving structures. The two-way validation process between experiments and theoretical modeling will lead to a rigorous understanding of molecular dynamics in the confining nanofluidic geometry.Broader Impacts: Owing to its cross-disciplinary nature, the proposed research will seamlessly integrate knowledge from distinct fields including micro/nanofabrication, micro/nanofluidics, hindered transport, polymer physics, and fluorescence imaging of single molecules. The proposed research, if successful, will foster transformative progress for separation of physiologically-relevant molecules using synthetic nanofluidic structures, a critical step toward fulfilling the promise of the nanofluidic proteomic research and future highly integrated bioanalysis micro/nanosystems. The proposed research will also lead to a thorough understanding of molecular dynamics in the confining nanofluidic geometry, which could provide a novel basis for ultra-sensitive and high-resolution sensors and medical diagnostic systems. The proposed educational activities will have broad impacts on students from different educational levels and genders and ethnicities. Some of the technologies described in the proposal will be used as vehicles for outreach activities to K-12 students and other underrepresented female and minority students in the Ann Arbor and Ypsilanti school districts. The proposed outreach activities will reveal to K-12 students the exciting challenges in science and engineering and their close relevance to our society, thus motivating them to pursue science and engineering curricula. For undergraduate and graduate education, an interdisciplinary course in Micro/Nanofluidics and BioMEMS will be developed. This course will prepare engineering students to pursue research in a variety of multidisciplinary areas such as BioMEMS and Lab-on- Chip, analytical chemistry, and micro/nanoscale materials sciences.