ADVANCED MEMS FOR HIGH THROUGHPUT DNA SEQUENCING

描述：（申请人摘要）微机电系统 （MEMS）被提出来可能彻底改变DNA测序。我们 提出一个流水线程序来实现一个完全自动化的， 小型化系统，用于此应用。自动化MEMS系统将 联合收割机结合了以往单车道和多车道的优点 由麻省理工学院开发的电泳系统， 广泛的发展，包括： 大面积（75mm x 170mm）分离元件采用玻璃制造， 硅采用MEMS技术，具有384个通道（100 μ m宽，40 μ m深 200 zm中心的通道） 压电驱动进样方法 线性聚丙烯酰胺筛分基质的无缺陷铸造， 多通道格式中400个碱基的单碱基分辨率 基于像增强CCD的侧面照明检测 带有碱基调用软件接口的读出器 该计划的关键技术组成部分是： 该系统能够并行运行384个车道，分辨率为 每条泳道400个碱基，运行时间约为1小时。这样的 全时操作的仪器将允许收集超过3M碱基的 每台机器每天的原始序列数据，或者大约 每周完成序列的4M个碱基（Sx冗余）。 原型仪器将在WVMIT基因组中心进行评估 research.测试需要与样品制备和 CGR的数据处理能力。我们将开始 24个月后进入序列生产线。 通过先进的驱动器进一步改进系统， 分辨率和吞吐量，微加工无机基质， 将采用硅系统。 一个重要的结构特征是整个团队的共同定位， 跨学科工程师，生物学家和化学家，广泛的 微加工设施和重要的遗传学实验室， 在一个单一的网站。

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.