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）：提出了一种新方法，用于通过直接电子测量单个碱基来测序单个DNA分子。该方法在新发现的悬浮的脂质双层构型中利用蛋白质孔，简单的电子模型和计算显示，在测量孔隙阻断电流的测量中提供了十倍的灵敏度提高。第二个关键的创新是将通过孔通过孔通过孔通过孔驱动DNA易位的手段的均值诱导离子电流的均值分开，从而可以单独优化每个易位。在第一阶段，将研究与第二个创新有关的关键问题，并预测完整系统的性能。在第二阶段，将评估将系统的所有要素以基本形式相结合的初步实验室。该计划是电子生物科学有限责任公司（EBS），开发新的超低噪声电子读数架构的开发者亨利·怀特（Henry White）教授，新的悬挂膜配置的发明者和戴维·迪姆教授，戴维·迪姆（David Deamer）的发明者，通过蛋白质孔的DNA易位科学的先驱。提出的DNA方法的直接电子测序可以使人基因组常规测序的能力。从理论上讲，该系统将允许在一个小时内测序30亿个哺乳动物基因组，比当前系统提高1000倍。这种快速的低成本测序可用于获取有关疾病和治疗易感性的个性化信息，从而彻底改变医学。

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.