Massively parallel linearization and chemical treatment of DNA molecules using tunable nanoscale confinement

点击翻译按钮获取中文摘要

Genetic analysis, such as DNA sequencing, has become an established technology for health science research, as well as disease prognosis and diagnosis. However, modern sequencing methods face considerable challenges, presenting key technology development opportunities. For instance, BCC Research expects the global sequencing market to grow to nearly $11.7 billion by 2018 and register an annual growth rate of 21.2% from 2013 to 2018. The technology underlying today's sequencing market dominant shareholder, Illumina, relies on breaking DNA into millions of tiny pieces, many orders of magnitude smaller than the genome. This fracturing process typically leads to a costly and error-prone process of reassembling the genome, and loss of long-range genomic information such as haplotype phase, copy number variation, and structural rearrangements that occur in cancer. Competing long-molecule technologies, as exemplified by Pacific Biosciences, are plagued by high error rates that render their results computationally impractical to use beyond niche applications. The aim of this proposal is to research, develop, and synthesize new technologies to sequence longer DNA strands than current technology and with lower error rates. We combine key expertise in nanoscale physics and single-molecule microscopy, microelectromechanical systems (MEMS) engineering, and labeling chemistry. This proposal kickstarts a relationship between three world-experts: the Leslie Laboratory at McGill University has pioneered novel single-molecule manipulation and visualization "CLiC" technology critical to gently untangling, linearizing and analyzing long DNA strands; Micralyne is a leading microfluidics and MEMS foundry in Canada, with extensive fabrication expertise key to miniaturizing Leslie's techniques; ZSGenetics has developed chemical processing approaches to label DNA base pairs for sensitive readout. The resources, training, insights and technologies delivered by this project would train high-quality personnel for growing the biotechnology sector in Canada, generating employment and revenue e.g. fabrication of consumables associated with the technology would be anchored in Micralyne (Edmonton, Canada).