$100,000 Genome Using Integrated Microfluidic CE

描述（由申请人提供）：该项目的目标是开发一个商业系统，用于使用微加工设备进行DNA测序，该系统将使全基因组哺乳动物测序成为可能，成本约为10万美元。自20世纪70年代以来，“分离测序”一直是DNA分析的实际方法；然而，目前使用毛细管电泳实现这一功能的商业系统不太可能超过全基因组测序成本约为500万美元的水平。该项目将支持商业系统的开发，这些系统将使用当前经过验证的基因组测序方法（即PCR和Sanger测序）提高DNA分离的性价比，超越毛细管系统所能达到的水平。目前的“装配线”测序需要昂贵的自动化和机器人技术，还要准备数百倍于电泳所需的昂贵样品和试剂。该项目将通过使用大规模微加工将各种组件步骤集成到大规模生物芯片设备中来消除这种需求。将开发特定的微加工系统和子系统，可以直接替代高通量和中等通量测序设施中的现有组件。微尺度流体过程的集成有望大幅降低成本，从而显著减少试剂消耗，并以专用微流体为基础的液体处理取代昂贵的液体处理自动化。

DESCRIPTION (provided by applicant): The objective of this project is to develop a commercial system for DNA sequencing using microfabricated devices that would enable whole-genome mammalian sequencing for about $100,000. "Sequencing by separation" has been the de facto method of DNA analysis since the 1970s; however current commercial systems that implement this using capillary electrophoresis are unlikely to be developed beyond the point where whole-genome sequencing will cost about $5,000,000. This project will support the development of commercial systems that will advance the price-performance of DNA separation using current, proven genome sequencing methodologies (i.e. PCR and Sanger sequencing) beyond that achievable with capillary systems. Current "assembly line" sequencing requires expensive automation and robotics, as well as the preparation of several hundred times the amount of expensive sample and reagent needed for electrophoresis. This project will eliminate the need for this by using large scale microfabrication to integrate the various component steps in a large scale biochip device. Specific microfabricated systems and sub-systems will be developed that can be deployed as direct replacements of existing components in high and medium-throughput sequencing facilities. Substantial cost reductions are expected from the integration of microscale fluid processes, leading to significant reductions in reagent consumption, and the replacement of expensive liquid-handling automation by dedicated microfluidics-based liquid-handling.