HIGH THROUGHPUT, HIGH RESOLUTION DNA SEQUENCING

我们的目标是开发一种高通量自动测序仪，适用于识别DNA分子混合群体中罕见的突变和多态，并以p53基因为模型系统对该仪器进行验证。这台机器的运行基于一种新的检测技术，该技术提供了混合荧光标记的超高分辨率。该机器的主要特点：。混合DNA样品的分析，分辨率为1%；产能600万个基点/年；标记的DNA材料含量低；易于更换的毛细管盒；适应不同染料组的颜色测序；在第一阶段，我们将演示混合DNA样本1%分辨率的可行性，并使用临床DNA材料测试该检测系统。在第二阶段，我们将开发机器的试点原型，并使用p53基因作为模型系统来验证机器。在第三阶段，我们将组织制造12个毛细管盒和12个通道的自动序列，用于混合DNA样本的诊断。拟议的商业应用：拟议的自动测序机将在遗传病的临床诊断中找到应用，主要是癌症。其精确量化受污染DNA样本的独特能力将确保在一个重要的细分市场中占据主导地位。

Our goal is the development of a high-throughput automated sequencing instrument adapted for identification of rarely present mutations and polymorphism in mixed populations of DNA molecules and validation of the instrument using the p53 gene as a model system. Operation of the machine is based on a novel detection technique which offers the ultra-high resolution of mixed fluorescent markers. Main features of the machine: . analysis of mixed DNA samples with 1% resolution; . throughput of 6,000,000 bp/year; . low amount of labeled DNA material; . Easy-to-replace capillary cassette; . adapted to color sequencing with different dye sets; In Phase 1 we shall demonstrate a feasibility of 1% resolution of mixed DNA samples and test this detection system using clinical DNA material. In Phase II we shall develop a pilot prototype of the machine and validate the machines using the p53 gene as a model system. In Phase III we shall organize manufacturing of the 12-capillary cassettes and 12-lane automated sequence for diagnostics of mixed DNA samples. PROPOSED COMMERCIAL APPLICATION: The proposed automated sequencing machine will find applications in clinical diagnostics of genetic disease, primarily cancer. Its unique capability to precisely quantify contaminated DNA samples will ensure a dominant position in an important market segment.