Development of a low cost solid-state nanopore fabrication method

纳米孔是嵌入在薄绝缘膜中的纳米级孔。它们提供了一个有限的空间，在这个空间内，单个分子可以被捕获并以高吞吐量进行电询问。经过15年的积极研究，基于纳米孔的传感器已成为下一代快速、低成本DNA测序技术的主要候选者。我们的设想是，纳米孔将直接从基因组DNA链中读取核苷酸序列，而不需要任何酶扩增或使用标记。这一成就将使基于纳米孔的DNA测序成为个性化医学的基石，允许对整个人类基因组进行廉价(1,000美元)、快速(24小时)的测序。基于纳米孔的技术作为一种用于疾病诊断应用的工具也有望产生重大影响，包括筛选蛋白质生物标记物，或分析microRNA的表达。 然而，纳米孔技术商业化的主要障碍是与固态纳米孔的制造相关的复杂性和成本。我们发现了一种新的方法来可靠地创建亚10 nm的纳米孔。开发的方法简单，成本低，易于大规模制造，与目前涉及高能粒子束的制造方法相比，这是一个重大进步。在这份提案中，我们与我们的工业合作伙伴一起，打算探索这种新的纳米制造方法的全部潜力，并证明它满足了生物医学诊断应用中所需的苛刻规格。所开发的技术将在固态纳米孔技术的生产方面为加拿大制造业提供竞争优势。此外，这个项目将为一批高素质的人才提供宝贵的多学科培训，这些领域包括纳米制造、流体学和生物传感，这些领域符合我们高科技生物医药行业的需求。这将有助于通过加强我们的知识经济，确保加拿大在这一领域保持竞争力。

Nanopores are nanometer-scale holes embedded in thin insulating membranes. They provide a confined space within which single molecules can be captured and electrically interrogated at high throughput. Following 15 years of active research, nanopore-based sensors have emerged as the leading candidate for the next-generation of rapid, low-cost DNA sequencing technologies. The vision is that a nanopore would directly read the sequence of nucleotides from a strand of genomic DNA without any enzymatic amplifications, or use of labels. This achievement would place nanopore-based DNA sequencing as the cornerstone of personalized medicine, allowing for inexpensive (<$1,000), rapid (<24h) sequencing of an entire human genome. Nanopore-based technologies are also expected to have a significant impact as a tool used in disease diagnostic applications, including screening protein biomarkers, or profiling microRNA expression. However, the major barrier to the commercialization of nanopore-based technologies is the complexity and cost associated with the fabrication of solid-state nanopores. We have discovered a novel method to reliably create sub-10-nm nanopores. The method developed is simple, low-cost and amenable to mass-fabrication, a major step forward compared to current fabrication methods involving high-energy beam of particles. In this proposal, together with our industrial partner, we intend to explore the full potential of this new nanofabrication method, and demonstrate that it addresses the demanding specifications required in biomedical diagnostic applications. The technology developed will provide Canadian manufacturing industry with a competitive advantage in the production of solid-state nanopore technologies. In addition, this project will offer valuable multidisciplinary training to a number of highly qualified personnel, in a variety of areas including nanofabrication, fluidics, and biosensing, which meet the demands of our high-tech biomedical industry. This will help ensure that Canada remains competitive in this sector by strengthening our knowledge-based economy.