Interrogating and Manipulating Biological Material at Small Scales

小规模询问和操纵生物材料

• 批准号: RGPIN-2020-05012
• 负责人: Godin, Michel
• 金额: $ 3.35万
• 依托单位: University of Ottawa
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=762622
• 关键词: Interrogating; Manipulating; Biological; Material; Small

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.

在开发新的生物物理分析能力方面取得的进展，为了解生命系统的生物状况提供了新的途径。我们在微米和纳米尺度上操纵流体的能力使我们能够设想新的分析设备，这些设备利用显着的小尺度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，因为它们能够以单分子灵敏度分析生物样品。固态纳米孔是细胞膜中发现的生物孔的合成类似物。这些纳米孔是纳米流体通道，其允许单个生物分子（例如DNA、RNA和蛋白质）从膜的一侧移位到另一侧。当用作传感器时，我们可以监测通过这种纳米孔的离子电流，以获得关于易位分子的丰富的物理和化学信息。除了在DNA测序中的应用外，这一概念在其他应用中表现出巨大的潜力，包括疾病诊断和单细胞信号传导的研究。 最近，我们发现了一种将这种纳米孔传感器集成到微流体网络中的方法。这为便携式芯片实验室分析平台的开发打开了大门，该平台通过提供芯片上的样品处理能力（过滤、混合、预浓缩等），可以容纳真实世界的样品。纳米孔传感器的上游。有趣的是，当被限制在微通道内时，纳米孔的性能会改变。在这个发现计划中，我们将研究集成在微通道中时在纳米孔附近发生的质量传输现象，并使用这些结果来调整传感器性能。此外，我们将利用我们的能力在纳米孔附近捕获皮升规模的样品，以实现生物分子浓度的准确定量，并且这个平台将能够在单细胞水平上研究细胞信号传导。这些发现将导致开发新的分析平台，通过分析超低浓度的生物标志物，极大地拓宽疾病诊断能力，同时还提供对单细胞生物学的深入了解。 在此DG周期中获得的知识和开发的技术可能会确保加拿大生物医学部门的全球竞争优势。我们的工作提供了一条发展即时诊断平台的道路，可以大大提高我们跟踪疾病的能力。此外，相关的跨学科培训无疑将为学生（HQP）提供科学和工程方面的广泛技能，同时专注于单分子技术，这在加拿大的高科技产业中需求不断增长。