Continuous Chromosome Sorting with Micro/nanofluidics

描述（由申请人提供）： 长基因组DNA的单分子分析将提供更多的基因组结构畸变/变异的知识，并提高对它们与癌症相关性的理解。该项目的长期目标是开发一种完全集成的芯片和阅读器，能够对大型天然状态基因组材料进行单分子分析。预期的实施方案将允许直接可视化和分析直接从样品（可能是单个细胞）中提取的DNA的染色体和巨噬细胞片段，其中亚甲基双酶分辨率。此外，该芯片将以高通量的方式容纳单个DNA分子的大规模并行分析，从而以及时的方式提供统计相关数据。 由于大多数疾病相关基因座位于特定染色体上，因此能够在纳米流体中进一步进行单分子水平分析之前对其进行预分选具有重要价值。为了帮助实现这一目标，我们建议研究将普林斯顿大学Sturm教授开发的微流体颗粒分选技术与BioNanomatrix的纳米流体DNA分析技术相结合的可能性。基于大规模并行方式的连续样品分析的微/纳流体标准化平台可以显著降低成本，并作为未来患者护理中一致的高通量基因组分析的基础。

DESCRIPTION (provided by applicant): Single molecule analysis of long, genomic DNA will provide greater knowledge of genomic structural aberrations/variations and improved understanding of their association with cancer. The long-term goal of this project is to develop a fully integrated chip and reader capable of single molecule analysis of large native state genomic material. The anticipated embodiment will permit direct visualization and analysis of chromosomal and megabase fragments of DNA extracted directly from a sample (possibly a single cell) with sub-kilobase resolution. Furthermore, the chip will accommodate massively parallel analyses of individual DNA molecules in a high- throughput manner thus providing statistically relevant data in a timely fashion. As most disease related loci are located on specific chromosomes, it is of great value to be able to pre-sort them prior to further single molecule level analysis in nanofluidics. In order to help reach this objective, we propose investigating the possibility of integrating microfluidic particle sorting technology developed under Prof Sturm at Princeton University with BioNanomatrix's nanofluidic DNA analysis technology. A micro/nanofluidic standardized platform based on continuous sample analysis in massive parallel fashion could dramatically reduce the cost and serve as a basis for consistent, high-throughput genomic analyses in future patient care.