Rapid nanopore-based single molecule counting for accurate concentration measurements

用于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。新技术已经出现，可以询问单个分子，为医疗保健提供重要的新机会。精准医疗时代的进一步发展需要实现两个关键标准。首先，新工具将需要超高的灵敏度，以便能够检测样品中目标生物标志物的几个拷贝。其次，如果检测结果被延迟，超灵敏度带来的早期检测的好处就会丧失，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向更快速、移动、低成本的现场检测。纳米孔传感是新兴超灵敏技术中最有前途的一种分散化技术。纳米孔本质上是单分子探测器，本质上完全是电的，不需要复杂、昂贵、笨重的光学元件和染料。因此，它们非常适合以小型化、便携化和分散化的形式提供超灵敏的检测。在本提案中，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准确定量生物标记物的检测极限，从而使基于纳米孔的超灵敏免疫分析技术的发展适合于护理点。这个项目是高度跨学科和独特的定位，以推进纳米孔传感领域，并加强加拿大在这个新兴领域和更大的纳米生物技术领域的利益。许多学生将面临为快速发展的市场合作开发先进技术的挑战。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。通过这个项目，加拿大人可以期待更好、更快、更精确和更方便的医疗保健，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.