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

研究单位：密歇根大学安娜堡分校智力优势：高效纳米流体筛分结构的发展是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的重要一步。鉴于目前纳米流控蛋白质组学的研究方向，了解纳米流控筛分环境下的分子转运特性变得至关重要。因此，本研究的主要目标是从实验和理论两方面研究限制纳米流体环境中的分子动力学，以及如何利用这些知识来设计用于高级生物分离的新型纳米流体筛分结构。不同的微纳米制造方法将被应用于生成亚100纳米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分离性能（如尺寸选择性和分离分辨率）如何受到纳米流体结构的不同结构参数和外电场的影响。实验结果将用于指导动力学模型的发展并进一步验证它们。反过来，理论建模的预测将用于激发新的分离分析，并指导改进的设计和几代纳米流体筛分结构。实验和理论建模之间的双向验证过程将导致在限制纳米流体几何分子动力学的严格理解。更广泛的影响：由于其跨学科性质，拟议的研究将无缝整合来自不同领域的知识，包括微/纳米制造，微/纳米流体，阻碍运输，聚合物物理学和单分子荧光成像。如果这项研究成功，将促进利用合成纳米流体结构分离生理相关分子的革命性进展，这是实现纳米流体蛋白质组学研究和未来高度集成的生物分析微/纳米系统的关键一步。该研究还将导致对限制纳米流体几何结构中的分子动力学的透彻理解，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斯兰蒂学区的K-12学生和其他代表性不足的女性和少数民族学生开展外展活动的工具。建议的外展活动将向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，将开发微/纳米流体和生物医学系统的跨学科课程。本课程将培养工科学生从事多种多学科领域的研究，如生物医学系统和芯片实验室、分析化学和微/纳米材料科学。

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.