Interrogating and Manipulating Biological Material at Small Scales

新的生物物理分析能力的发展进步提供了对生命系统的生物条件的新见解。我们在微观和纳米尺度上操纵流体的能力使我们能够构想出新的分析设备，利用显著的小规模现象来减轻传统传感平台中发现的一些问题。在过去的十年中，纳米孔传感器已经成为最有前途的下一代分析工具之一，因为它们具有单分子灵敏度分析生物样品的能力。固态纳米孔是合成的类似于在细胞膜上发现的生物孔。这些纳米孔是纳米流体通道，允许单个生物分子（如DNA、RNA和蛋白质）从膜的一边转移到另一边。当用作传感器时，我们可以通过这些纳米孔监测离子电流，从而获得有关易位分子的丰富的物理和化学信息。除了在DNA测序中的应用，这一概念在其他应用中也显示出巨大的前景，包括疾病诊断和单细胞信号的研究。

Advances in the development of novel biophysical analytical capabilities provide access to new insight into the biological condition of living systems. Our ability to manipulate fluids at the micro- and the nano-scales is allowing us to conceive of new analytical devices that utilize remarkable small-scale phenomena in mitigating some of the issues found in conventional sensing platforms. In the last decade, nanopore sensors have emerged as one of the most promising next-generation analytical tools given their ability to analyze biological samples with single-molecule sensitivity. Solid-state nanopores are synthetic analogs to the biological pores found in cell membranes. These nanopores are nanofluidic channels that allow the translocation of single biomolecules, such as DNA, RNA and proteins, from one side of a membrane to the other. When used as sensors, we can monitor the ionic current through such nanopores in order to gain a wealth of physical and chemical information about the translocating molecule. In addition to its use in DNA sequencing, this concept exhibits great promise in other applications including disease diagnostics and the study of single-cell signaling. Recently, we discovered an approach to integrating such nanopore sensors within microfluidic networks. This has opened the door to the development of portable lab-on-a-chip analytical platforms that can accommodate real-world samples, by offering on-chip sample processing capabilities (filtering, mixing, pre-concentrating, etc.) upstream of the nanopore sensor. Intriguingly, nanopore performance is altered when confined within microchannels. In this Discovery program, we will investigate the mass transport phenomena that occur near the nanopores when integrated within microchannels, and use these results to tune sensor performance. Also, we will use our ability to trap picolitre-scale samples near the nanopore to enable the accurate quantification of biomolecular concentration, and this platform will enable the study of cell signaling at the single cell level. These discoveries will lead to the development of new analytical platforms that will greatly broaden disease diagnostic capabilities by enabling the analysis of ultra-low concentration biomarkers, while also providing insight into the biology of single cells. The knowledge acquired and the technologies developed over this DG cycle could potentially secure a global competitive edge for the Canadian biomedical sector. Our work provides a path towards the development of point-of-care diagnostics platforms that could greatly enhance our ability to track disease. Moreover, the associated interdisciplinary training will undoubtedly provide students (HQP) with a broad skillset in science and engineering while focusing on single-molecule techniques, which are in growing demand in Canada's high-tech industry.