New Method for Direct Electronic Sequencing of DNA

DNA 直接电子测序新方法

• 批准号: 7649805
• 负责人: ANDREW D HIBBS
• 金额: $ 10.51万
• 依托单位: ELECTRONIC BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-19 至 2008-09-10
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7649805
• 关键词: Address; Affect; Amplifiers; Architecture; Biology; Blood capillaries; Collaborations; Conflict (Psychology); DNA; DNA Sequence; Development; Diffusion; Disease; Electric Capacitance; Electronics; Elements; Frequencies; Glass; Hemolysin; Hour; Human Genome; Individual; Investigation; Laboratories; Length; Lipid Bilayers; Localized; Location; Measurement; Measures; Medicine; Membrane; Methods; Modeling; Motion; Noise; Performance; Phase; Pore Proteins; Predisposition; Property; Rate; Science; Signal Transduction; Staging; Standards of Weights and Measures; System; Systems Theory; Temperature; Testing; Thick; Time; base; capillary; computerized data processing; cost; design; driving force; innovation; mammalian genome; nanoscale; novel; novel strategies; patch clamp; professor; programs; research study; synthetic construct; voltage

DESCRIPTION (provided by applicant): A new method is proposed for sequencing a single DNA molecule via direct electronic measurement of individual bases. The method utilizes a protein pore in a newly discovered suspended lipid bilayer configuration that simple electronic models and calculations show offers a factor of ten sensitivity improvement in measurement of the pore blocking current. A second key innovation is to separate the means used to induce the ionic current through the pore from the means used to drive DNA translocation through the pore, allowing each to be optimized separately. In Phase I the key questions relating to the second innovation will be investigated and the performance of a complete system projected. In Phase II, a preliminary laboratory apparatus that combines all elements of the system in a basic form will be evaluated. This program is a collaboration between Electronic Bio Sciences LLC (EBS), pioneers in the development of new ultra low noise electronic readout architectures for biology, the group of Professor Henry White, the inventors of the new suspended membrane configuration, and Professor David Deamer, a pioneer in the science of DNA translocation through protein pores. The proposed direct electronic sequencing of DNA method could allow the ability for routine sequencing of the human genome. In theory this system would allow a 3 billion base mammalian genome to be sequenced in under an hour, a 1000 times improvement over current systems. Such rapid low cost sequencing could be used to obtain individualized information on predisposition to diseases and treatments and could thereby revolutionize medicine.

描述（由申请人提供）：提出了一种通过直接电子测量单个碱基对单个DNA分子进行测序的新方法。该方法利用蛋白质孔在一个新发现的悬浮脂质双层配置，简单的电子模型和计算表明，提供了一个因素的10灵敏度提高测量的孔阻塞电流。第二个关键创新是将用于诱导离子电流通过孔的手段与用于驱动DNA易位通过孔的手段分开，允许分别优化每种手段。在第一阶段，将调查与第二次创新有关的关键问题，并预测完整系统的性能。在第二阶段，将评估一个初步的实验室设备，该设备将系统的所有元素结合在一个基本的形式。该计划是电子生物科学有限责任公司（EBS），在新的超低噪声电子读出架构的生物学开发的先驱，教授亨利白色，新的悬浮膜配置的发明者，和教授大卫迪默，通过蛋白质孔的DNA易位科学的先驱之间的合作。所提出的DNA直接电子测序方法可以允许常规测序人类基因组的能力。从理论上讲，该系统可以在一小时内对30亿个哺乳动物基因组进行测序，比目前的系统提高了1000倍。这种快速低成本的测序可以用来获得关于疾病易感性和治疗的个性化信息，从而可以彻底改变医学。

项目成果

Monitoring the escape of DNA from a nanopore using an alternating current signal.

• DOI: 10.1021/ja906951g
• 发表时间: 2010-02-17
• 期刊: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
• 影响因子: 15
• 作者: Lathrop, Daniel K.;Ervin, Eric N.;Barrall, Geoffrey A.;Keehan, Michael G.;Kawano, Ryuji;Krupka, Michael A.;White, Henry S.;Hibbs, Andrew H.
• 通讯作者: Hibbs, Andrew H.