MULTI PARAMETER ANALYSIS OF MRNA LEVELS IN LUNG TISSUE

该计划项目将开发一套新的整合核酸 杂交技术：寡核苷酸、表面和染料化学、 一种新型的高速微阵列--流控方法 杂交分析的格式以及一种新型的高速电荷耦合器件 基于检测平台。这项工作是技术的延伸 由商务部ATP计划资助的开发 它已经产生了大量的出版物和专利 “生物芯片”区。这里的目标是大大扩展这种生物芯片 临床肺肿瘤基因分析的技术基础 背景。这项工作是由两个生物学原理驱动的。第一 就是，要想在临床上发挥作用，杂交技术必须 要非常快速和灵敏，但相对便宜和简单 足以确保严格的质量控制并轻松集成到可用高 吞吐量样本处理机器人。第二条原则，推动 这项工作是为了让癌症诊断真正发生革命性的变化 技术必须能够获得几种不同类型的 每天的遗传信息，在同一样本上，以并行的方式。 根据这些原则，我们提出了一个技术平台，该平台 每个工作站每天可以处理数百个样本，并将 在以下规模的每个肿瘤上生成不同类型的数据集： 点突变(最多3个基因)、杂合性缺失(最多10个基因座)、 基因在mRNA水平上的表达(每个样本多达100个基因)。 为了实现这些集成技术目标，我们组建了一个团队 在核酸和表面化学方面有创新的记录 (项目1)，核酸和表面的超级计算机模拟 相互作用(项目2)、创新的光学探测器和微流体 工程(项目3)、工作站集成(核心A)、癌症 分子生物学、肿瘤病理学和组织档案管理 (核心B)和多学科研究协调(核心C)。

This Program Project will develop a novel set of integrated nucleic acid hybridization technologies: oligonucleotide, surface and dye chemistry, fluidic methods for high speed microarry fabrication, a new microarry format for hybridization analysis and, finally, a novel high speed CCD based detection platform. The work is an extension of technology development which was funded by the Department of Commerce ATP program and which has already generated numerous publications and patents in the "biochip" area. The goal here is to greatly extend this biochip technology base for genetic analysis of lung tumors in a clinical context. The work is driven by two biological principles. The first is that, to be useful in the clinic, the hybridization technology must be very fast and sensitive, but relatively inexpensive, and simple enough to ensure rigorous QC and easy integration into available high throughput sample handling robotics. The second principle which drives the work is that the order to truly revolutionize cancer diagnosis, the technology must be capable of obtaining several different types of genetic information per day, on the same sample, in parallel fashion. In accord with those principles, we propose a technology platform which can process several hundred samples per day per workstation, and will generate heterogeneous data sets on each tumor of the following scale: point mutation (up to 3 genes), LOH (up to 10 loci), quantitation of gene expression at the MRNA level (as many as 100 genes per sample). To achieve those integrated technology goals, we have assembled a team with a record of innovation in nucleic acid and surface chemistry (Project 1), supercomputer modeling of nucleic acid and surface interactions (Project 2), innovative optical detector and microfluidics engineering (Project 3), workstation integration (Core A), cancer molecular biology, tumor pathology and tissue archive administration (Core B) and multidisciplinary research coordination (Core C).