MICROMECHANICAL INTEGRATED DNA ANALYSIS TECHNOLOGY

该项目是自1993年以来三个研究小组合作的延续。成功的跨学科团队代表了化学合作小组的知识，专注于开发具有完整过程集成的微制造DNA分析设备。继续提案将开发一种完全集成的DNA样本处理和分析技术，用于基因分型和测序。提取遗传信息的所有步骤都将在一个独立的系统中进行，具有最小的操作员交互。该系统的微流体、光学和电子元件在硅、硅/玻璃或硅/聚合物基板上制造，产生微机械集成DNA分析技术。为了确保低廉的设计、测试和生产成本，这些器件将采用光刻构造技术制造。一种能够以每个碱基低于0.01美元的总成本生成原始DNA序列的基因组测序设备的目标是在五年内完成。该提案有四个项目目标：1)设计，构建和评估集成DNA分析系统。系统级方法将用于评估该项目开发的所有组件和制造技术。成功与否将以完整的基因分型和测序系统的水平来衡量。（项目1）设计、构建和评估改进的微流体、微反应和微分离。多步骤处理和反应将在微加工设备上进行测试。将设计和测试先进的凝胶电泳系统，测序至阅读长度>500 bp。（项目2）开发集成微系统的改进制造方法和光学传感器。薄膜沉积聚合物和微模塑聚合物将被检查用作基材和水密通道。将设计和测试光学传感器，以提高灵敏度和稳定性。（项目3）为复杂集成微流体装置的建设和测试提供设施和支持。将维持一个中央装配和测试设施，以便为每个项目迅速建造和测试原型和逐步改进（核心股）。

This Program Project is the continuation of collaboration between three research groups that have been working together since 1993. The successful interdisciplinary team represents knowledge in chemical collaborative group has focused on the development of microfabricated DNA analysis devices with complete process integration. The continuation proposal will develop a fully integrated DNA sample handling and analysis technology for genotyping and sequencing. All the steps for extracting genetic information will occur within a single self-contained system having minimal operator interaction. The microfluidic, optical, and electronic components of the system are fabricated on silicon, silicon/glass, or silicon/polymer substrates, yielding a micromechanical integrated DNA analysis technology. To ensure inexpensive design, testing, and production, the devices will be made using photolithographic construction techniques. A genomic sequencing device capable of generating raw DNA sequence at less than $0.01 total costs per base is targeted for completion in five years. The proposal has four Program Goals: 1) Design, construct, and evaluate integrated DNA analysis systems. A system-level approach will be used to evaluate all components and fabrication technologies developed by the Program Project. Success will be measured at the level of complete genotyping and sequencing system. (Project 1) 2) Design, construct, and evaluate improved microfluidics, microreactions, and microseparations. Multistep handling and reactions will be tested on microfabricated devices. Advanced gel electrophoresis systems for sequencing t read-length >500 bp will be designed and tested. (Project 2) 3) Develop improved fabrication methods and optical sensors for integrated microsystems. Thin film deposited polymer and micromolded polymer will be examined for use as substrates and water-tight channels. Optical sensors will be designed and tested for improved sensitivity and stability. (Project 3) 4) Provide facilities and support for construction and testing of complex, integrated microfluidic devices. A central assembly and testing facility will be maintained that can rapidly build and test prototypes and incremental improvements for each of the projects (Core Unit).