LOW VISCOSITY SEPARATION MEDIA FOR DNA SEQUENCING

目前的高通量DNA测序系统可以产生序列 数据的理论速率约为每年29兆字节。 毛细管阵列电泳（CAB）系统可以增加DNA 测序通量的数量级超过目前 可用的系统。可流动的分离介质是关键之一 CAB系统的组件，以及分离介质的改进 大大降低了CAB系统的成本。中到高 先前研究人员使用的分离介质的粘度 使得设计加压毛细管成为一项艰巨的任务 用于商用CAB系统的加气站。第一阶段的目标 该建议的一个重要目的是开发低粘度介质， 使单碱基分辨率达到1000个碱基。使用 低粘度分离介质将简化压力容器 CAB系统的设计问题，导致大量的 降低成本。这种高通量CAB系统的使用将 彻底改变大规模测序项目， 降低每个基地的成本。第二阶段的研究将扩大效用 低粘度和高分辨率介质， 动态涂层毛细管， 高成本的共价涂层毛细管。这将进一步减少 每个系统和每个碱基序列的成本。 建议的商业应用：CAE系统具有重要的 提高美国经济增长和生产力的潜力， 加速了新基因信息的产生。 可靠的、具有成本效益的测序和基因分型将使 对人类基因组计划，医疗保健， 农业综合企业、法医分析和制药业。

Current high-throughput DNA sequencing systems can produce sequence data at a theoretical rate of approximately 29 megabases per year. Capillary Array Electrophoresis (CAB) systems can increase the DNA sequencing throughput by an order-of-magnitude over currently available systems. A flowable separation medium is one of the key components of the CAB system, and improvements in separation media significantly lower the cost of a CAB system. The moderate-to-high viscosities of the separation media used by previous researchers makes it a formidable task to design a pressurized capillary refilling station for a commercial CAB system. The goal of Phase I of this proposal is to develop low-viscosity media which will enable single base resolution out to 1000 bases. Using low-viscosity separation media will simplify the pressure-vessel design issues of the CAB system, resulting in a substantial reduction in cost. Use of such high-throughput CAB systems will revolutionize large-scale sequencing projects, and substantially reduce the cost per base. Phase II studies will extend the utility of low-viscosity and high-resolution media with less expensive dynamically-coated capillaries by eliminating the need for high-cost covalently-coated capillaries. This will further reduce the cost per system and per base sequences. PROPOSED COMMERCIAL APPLICATIONS: A CAE system has significant potential to improve the U.S. economic growth and productivity by accelerating the rate that new genetic information is generated. Reliable, cost-efficient sequencing and genetic typing will have significant impact on Human Genome Project, healthcare, agribusiness, forensic analysis, and pharmaceutical industry.