Carbon Nanotubes: Artifical Gels for Mutations Detection

描述（由申请人提供）： 我们的愿景是将联合收割机纳米技术与经过验证的基因筛选相结合 提供非侵入性、低成本、快速筛查特异性 癌症的分子特征高灵敏度和特异性，DOVAM-S （检测几乎所有的突变-SSCP）能够筛选几个 几乎100%准确的检测人类基因突变。的关键技术 展示的是一种纳米制造的电泳微器件， 几乎所有类型的突变和多态性。有了这项技术， 癌症易感性的成本效益筛查可以在 相对短期而言。基于碳纳米管的独特性质， 设想具有显著减少的试剂的集成纳米DOVAM-S系统 体积，缩短扩增和分离时间，自动读数 和结果的解释。在这份提案中，我们提出了这一愿景， 概念验证演示的必要步骤：首先证明 碳纳米管阵列的SSCP是可能的， DOVAM-S临床突变标准的建立及比较 筛选实验开发芯片上DNA分析的其他努力 技术缺乏区分DOVAM-S和 突变筛查的竞争方法。这些几乎是100%的 检测率和多重样品的能力。为了有效， 通过DOVAM-S进行突变筛选需要电泳分离单个- 有无突变的DNA链我们的方法是利用碳 纳米管作为电泳用固态纳米尺度筛 单链DNA的分离，取代交联聚合物， 常规凝胶电泳。提供芯片上DNA的竞争努力 分析保留使用交联聚合物，许多是基于 杂交反应，不能达到100%检测突变 这一点在这里所提倡的DOVAM-S方法中得到了证明。纳米DOVAM- S将使用人因子VIII和IX基因以及ATM基因进行验证， 在某些癌症中发生突变

DESCRIPTION (provided by applicant): Our vision is to combine nanotechnology with proven genetic screening technology to provide non-invasive, low cost, rapid screening for specific molecular signatures of cancer. Highly sensitive and specific, DOVAM-S (Detection of Virtually All Mutations-SSCP) is capable of screening several human genes for mutations with virtually 100% accuracy. The key technology to be demonstrated is a nanofabricated, electrophoretic microdevice for detecting mutations and polymorphisms of virtually all types. With this technology, cost-effective screening for cancer predisposition could be implemented in the relatively near term. Based on the unique properties of carbon nanotubes, we envision an integrated nano-DOVAM-S system with significantly reduced reagent volumes, shortened amplification and separation times, and automated readout and interpretation of results. In this proposal, we present this vision, and the necessary steps toward a proof-of-concept demonstration: first proving that SSCP is possible with carbon nanotube arrays, followed by protocol development and comparison with standard DOVAM-S in clinical mutation screening experiments. Other efforts to develop on-chip DNA analysis technology lack the essential advantages that distinguish DOVAM-S from competing approaches to mutation screening. These are a virtually 100% detection rate and the ability to multiplex samples. In order to be effective, mutation screening by DOVAM-S requires electrophoretic separation of single- stranded DNA with and without mutations. Our approach is to use carbon nariotubes as a solid-state nanometer-scale sieve for electrophoretic separation of single-strand DNA, replacing the cross-linked polymers used in conventional gel electrophoresis. Competing efforts to provide on-chip DNA analysis retain the use of cross-linked polymers, and many are based on hybridization reactions, which cannot attain the 100% detection of mutations that has been demonstrated in the DOVAM-S approach advocated here. Nano-DOVAM- S will be validated using the human factor VIII and IX genes and the ATM gene, mutated in certain cancers.