MICROMECHANICAL INTEGRATED DNA ANALYSIS TECHNOLOGY

该方案项目是自1993年以来一直合作的三个研究小组之间合作的继续。成功的跨学科团队代表了化学协作小组的知识，专注于开发具有完整工艺集成的微制造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，操作员的交互最少。该系统的微流控、光学和电子元件被制造在硅、硅/玻璃或硅/聚合物衬底上，从而产生了微机械集成DNA分析技术。为了确保低成本的设计、测试和生产，这些器件将使用光刻构造技术制造。一个基因组测序设备能够以每个碱基不到0.01美元的总成本产生原始DNA序列，目标是在五年内完成。该提案有四个计划目标：1)设计、构建和评估综合DNA分析系统。将使用系统级方法来评估该计划项目开发的所有部件和制造技术。成功与否将在完整的基因分型和测序系统的水平上进行衡量。(项目1)2)设计、建造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型制造设备上进行测试。将设计和测试先进的凝胶电泳系统，用于对t读数长度和500个碱基进行测序。(项目2)3)为集成微系统开发改进的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用作基材和防水通道。光学传感器将进行设计和测试，以提高灵敏度和稳定性。(项目3)4)为复杂、集成的微流控装置的建造和测试提供设施和支持。将维持一个中央组装和测试设施，以快速建立和测试每个项目(核心单位)的原型和增量改进。

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).