Rapid nanopore-based single molecule counting for accurate concentration measurements

健康和生命科学的科学仪器，特别是诊断学，正在经历一场革命。出现了可以审问单个分子的新技术，从而在医疗保健领域创造了重要的新机会。迈向精准医学时代的进一步进展需要实现两个关键标准。首先，新的工具将需要极高的灵敏度，以便能够在样本中仅检测到几个目标生物标记物的拷贝。其次，如果结果延迟，可能会失去导致早期检测的超敏感性的好处，并且错过了使用这些结果进行及时干预的机会，因此这些工具还必须使检测大众化，从传统的集中式核心实验室转移到更快速、更灵活、更低成本的现场测试。纳米孔传感是最有前途的新兴超灵敏技术，可以去中心化。纳米孔本质上是单分子探测器，本质上完全是电学的，不需要复杂、昂贵和庞大的光学部件和染料。因此，它们特别适合于以小型化、便携和分散的形式提供超灵敏检测。在这项建议中，我们将解决主要的“控制点”，通过提高单个分子的计数速度来降低生物标志物准确定量的检测极限，从而使基于纳米孔的超灵敏免疫分析技术能够得到开发。该项目具有高度的跨学科和独特的定位，以推进纳米孔传感领域，并加强加拿大在这一新兴领域和更大的纳米生物技术部门的股份。许多学生将面临合作开发先进技术以适应快速发展的市场的挑战。加拿大经济也将直接受益，因为我们的合作伙伴和其他行业参与者将把这一创新和未来的创新商业化。有了这个项目，加拿大人可以期待更好、更快、更精确、更方便的医疗保健，特别是在偏远地区。

Scientific instrumentation for Health and Life sciences, particularly diagnostics, is undergoing a revolution. New technologies have emerged that can interrogate individual molecules to enable important new opportunities in healthcare. Further progress toward the era of precision medicine requires the realization of two critical criteria. First, new tools will require ultrasensitivity, to enable detection of just a few copies of a target biomarker in a sample. Second, since the benefit of ultrasensitivity leading to early detection can be lost if the results are delayed and the opportunity to use those results for timely intervention is missed, these tools must also democratize detection, moving from a traditional centralized core lab to more rapid, mobile, low-cost testing on site. Nanopore sensing is the most promising emerging ultrasensitive technology that is amenable to decentralization. Nanopores are inherently single molecule detectors and are entirely electrical in nature, with no need for complex, expensive, and bulky optical components and dyes. As such, they are uniquely suited to provide ultrasensitive detection in a miniaturized, portable and decentralized format.In this proposal, we will address the main 'control points' that would enable the development of an ultrasensitive nanopore-based immunoassay technology amenable to the point of care, by increasing the counting speed of individual molecules to lower the limit of detection for accurate quantification of biomarkers. This project is highly interdisciplinary and uniquely positioned to advance the nanopore sensing field, and to strengthen the Canadian stake in this emerging area and in the larger nanobiotechnologies sector. Many students will be exposed to the challenges of collaboratively developing advanced technology for a rapidly-evolving market. The Canadian economy will also directly benefit as this and future innovations will be commercialized by our partner and other industry players. With this project, Canadians can look forward to better, faster, more precise, and more convenient healthcare, especially in remote settings.