ELUCIDATING the FUNDAMENTALS of BIOMOLECULAR TRANSPORT through NANOPORES

在受限几何结构中的动态现象，包括带电生物聚合物通过纳米级孔隙的传输，是生命的基本过程。分子通过纳米孔转运的生物学例子包括mRNA通过核孔复合物；分泌：蛋白质穿过细胞膜的分泌；以及注射病毒DNA在体内，这种转运是通过与细胞膜和/或特定蛋白质的相互作用来主动控制的。阐明控制纳米孔传输现象的物理过程是一个丰富的研究领域，控制通道的策略将找到许多技术应用。******在过去的十年中，纳米流体装置在开发仿生系统和研究单分子水平的运输过程方面取得了重大进展。特别是，通过研究核酸通过固态纳米孔（ssNP）获得了令人兴奋的结果。ssNP是介电薄膜上的纳米大小的孔，它已经成为研究涉及DNA和蛋白质的广泛现象的通用工具。基本概念依赖于监测离子电流的变化，以提供有关易位分子的物理和化学信息。除了DNA测序，这一概念在其他应用中也有很大的应用前景，包括分子计数；对DNA分子局部结构的扫描，或对单个生物分子相互作用的研究。然而，当前ssNP器件有限的时空分辨率和/或捕获效率阻碍了这些器件在实际应用中的实现。克服这些限制的创新解决方案将从对聚合物通过单核苷酸多态性易位动力学的更深入理解中出现。为此，本研究计划将重点放在通过实验阐明通过纳米孔控制生物分子运输现象的物理过程的长期目标上。目标将是开发新的策略或设备来控制捕获率和操纵分子在传递过程中的运动，并最终将这些发现转化为表征单分子过程和研究生命基本过程的新工具。******在这个5年的项目过程中产生的新知识可能会为加拿大生物医学工业在固态纳米孔技术的发展中获得全球竞争优势。此外，该项目还将在一系列尖端单分子技术方面为高素质人员（HQP）提供有价值的多学科培训。这些技能将使HQP能够满足我们日益增长的高科技产业的需求，从而加强加拿大的知识型经济，并确保其研究投资的最大回报

Dynamic phenomena in confined geometries, including the transport of charged biopolymers through nanoscale pores, are fundamental processes of life. Biological examples of molecular translocation through nanopores include the passage of mRNA through the nuclear pore complex; the secretion of proteins across cell membranes; and the injection of DNA from viruses. In vivo, such transport is actively controlled by interactions with cellular membranes and/or specific proteins. Elucidating the physical processes that govern nanopore transport phenomena is a fertile field of research, and strategies for controlling passage will find numerous technological applications. ******The last decade has seen significant advancements in nanofluidic devices to develop biomimetic systems and to study transport processes at the single-molecule level. In particular, exciting results have been obtained through the study of passage of nucleic acids through solid-state nanopores (ssNP). ssNP are nanometer-sized holes in thin dielectric membranes, which have emerged as a versatile tool to investigate a wide range of phenomena involving DNA and proteins. The basic concept relies on monitoring ionic current changes to provide physical and chemical information about the translocating molecule. In addition to DNA sequencing, this concept exhibits great promise for other applications, including molecular counting; scanning of local structures along DNA molecules, or the investigation of single biomolecular interactions. However, the limited spatiotemporal resolution and/or capture efficiency of current ssNP devices hinder these implementation for real-world applications. Innovative solutions to overcome these limitations will emerge from a deeper understanding of the dynamics of translocation of polymers through ssNP. To this end, this research program will be focused on the long-term objective of experimentally elucidating the physical processes governing biomolecular transport phenomena through nanopores. The goal will be to develop novel strategies or devices for gaining control over capture rate and manipulating molecular motion during passage and, ultimately, to translate these discoveries into new tools to characterize single-molecule processes and to study fundamental processes of life. ******The new knowledge generated over the course of this 5-year program could potentially secure a global competitive edge for Canada biomedical industry in the development of solid-state nanopore technologies. In addition, this program will offer valuable multidisciplinary training to highly qualified personnel (HQP) in a range of cutting-edge single-molecule techniques. These skills would position HQP to meet the demands of our growing high-tech industry, thereby strengthening Canada's knowledge-based economy and ensuring maximum return from its research investments.**