HIGH THROUGHPUT, HIGH RESOLUTION DNA SEQUENCING

我们的目标是开发一种高通量的自动测序仪器，适用于鉴定混合人群的DNA分子中很少存在的突变和多态性，并使用p53基因作为模型系统验证该仪器。 机器的操作基于一种新的检测技术，该技术提供混合荧光标记物的超高分辨率。 机器的主要特点：以1%的分辨率分析混合DNA样品; 6，000，000 bp/年的吞吐量;。 少量的标记的DNA材料; 易于更换的毛细管盒; 适用于不同染料组的颜色测序;在第1阶段，我们将证明混合DNA样本分辨率为1%的可行性，并使用临床DNA材料测试该检测系统。 在第二阶段，我们将开发一个试点原型的机器和验证的机器使用p53基因作为模型系统。 在第三阶段，我们将组织生产用于混合DNA样本诊断的12道毛细管试剂卡和12道自动测序。拟定商业应用：拟议中的自动测序机将在遗传疾病（主要是癌症）的临床诊断中找到应用。 其精确定量污染DNA样本的独特能力将确保在重要市场领域的主导地位。

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.