ADVANCED MEMS FOR HIGH-THROUGH PUT DNA SEQUENCING

描述：(申请人摘要)微电子机械系统 (MEMS)的提出可能会给DNA测序带来革命性的变化。我们 提出一种流水线程序来实现全自动化、 这个应用的小型化系统。自动化的MEMS系统将 结合了以往单车道和多车道的最佳特性 麻省理工学院开发的来自世界各地的电泳仪- 广泛的发展，包括： 大面积(75 Mm X 170 Mm)分离元件，采用玻璃和 采用MEMS技术的硅，具有384个通道(100 RM宽，40 Wm深 200 zm中心的频道) 压电驱动样品注入方法 一种线型聚丙烯酰胺筛分基质的无缺陷浇注 多通道格式，400个基数时的单基数分辨率 基于侧面照明与图像增强型CCD耦合的检测 带有与基调用软件接口的读数 该计划的关键技术组件包括： 一种能够并行运行384条车道的系统，分辨率为 每条赛道有400个基地，运行时间约为一个小时。这样的一种 全职操作的仪器将允许收集超过300万个基数 每台机器每天的原始序列数据，或大约 每周完成序列的4M个碱基(以SX冗余)。 原型仪器将在WVMIT基因组中心进行评估 研究。测试需要与样品制备和 CGR的数据处理能力。我们将开始试点插入 24个月后进入序列生产线。 通过高级驱动进一步改进系统，以实现更好的性能 分辨率和吞吐量，微型制造的无机基质，并按比例 将实施硅系统。 一个重要的结构特征是整个团队位于同一地点 跨学科的工程师、生物学家和化学家，广泛 微型制造设施和一个重要的遗传学实验室，所有这些 在一个地点。

DESCRIPTION: (Applicant's abstract) Microelectromechanical Systems (MEMS) are posed to potentially revolutionize DNA sequencing. We propose a stream- lined program to implement a fully automated, miniaturized system for this application. The automated MEMS system will combine the best features of previous single and several-lane electrophoresis systems developed at MIT and as derived from the world- wide development including: Large-area (75mm x 170mm) separation element fabricated in glass and silicon using MEMS technology with 384 lanes (100 Rm wide, 40 Wm deep channels on 200 zm centers) Piezoelectrically-driven sample injection methods Defect free casting of linear polyacrylamide sieving matrix capable of single-base resolution at 400 bases in multi-lane format Detection based on side-illumination coupled to image-intensified CCD readout with interface to base-calling software Key technology components of the program are: A system capable of running 384 lanes in parallel, with a resolution of 400 bases per lane and run times of approximately one hour. Such an instrument operated full time will allow collection of over 3Mbases of raw sequence data per day per machine, or the potential assembly of about 4Mbases (at Sx redundancy) of finished sequence per week. The prototype instrument will be evaluated in the WVMIT Center for Genome Research. The testing entails integration with sample preparation and data handling capabilities at the CGR. We will begin pilot insertions into the sequence production line after 24 months. Further system improvements through advanced drive for improved resolution and throughput, microfabricated inorganic matrices, and scaled silicon systems will be implemented. An Important structural feature is the co-location of the full team of cross disciplinary engineers, biologists and chemists, extensive microfabrication facilities, and an important genetics laboratory, all at a single site.