Large-Scale Nanopore Arrays for DNA Sequencing

用于 DNA 测序的大规模纳米孔阵列

• 批准号: 7490729
• 负责人: Carlos H Mastrangelo
• 金额: $ 11.15万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-26 至 2008-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7490729
• 关键词: Amplifiers; Arts; Bacterial Genome; Binding; Biological; Biological Sciences; Buffers; Characteristics; Collection; Compatible; DNA; DNA Sequence; Detection; Development; Devices; Discrimination; Electric Capacitance; Electrodes; Electronics; Environment; Facility Construction Funding Category; Family; Family Sizes; Film; Funding; Hemolysin; Human Genome; Individual; Investigation; Ion Channel Protein; Ions; Laboratories; Length; Location; Measurement; Measures; Membrane; Methodology; Methods; Molecular; Physics; Process; Purines; Rate; Relative (related person); Reporting; Research; Research Personnel; Risk; Rotation; Scheme; Side; Signal Transduction; Silicon; Single-Stranded DNA; Solutions; Speed; Structure; System; Systems Integration; Techniques; Testing; Time; Today; Work; base; day; desire; detector; dipole moment; driving force; macromolecule; migration; nanopore; nanoscale; novel; programs; purine; sensor

DESCRIPTION (provided by applicant): Today, synthetic nanopore devices are the subject of intense investigation as intriguing candidate devices for high-speed non-enzymatic interrogation of individual biological macromolecules. Such functionality is required for example in order to sequence individual DNA fragments of unknown composition at high speeds. While many theoretical aspects regarding macromolecule translocation physics and novel readout schemes are presently under investigation by several NIH-funded groups, the practical utilization of nanopores in sequencing systems also requires large arrays of nanopores working in parallel, each of these connected to high-sensitivity electronic amplifiers/detectors. Such degree of parallelism and systems integration is necessary in order to achieve significant improvements in throughput compared with today's state-of-the-art massively-parallel enzymatic sequencing by synthesis schemes (SBS) (such as those offered by 454 Life Sciences which reports high-fidelity sequencing of bacterial genomes at 20 Mb/day). To illustrate the need for arrays one may consider for example, a 100- nanopore array with average nanopore translocation rate of 100b/ms/pore could in principle sequence fragments at (high-fidelity, 100 repeats) rates of 10 Gb/day, allowing an entire human genome to be sequenced in a day, 500 times faster than SBS. The aims of this proposal are (a) the development of highly-integrated arrays of nanopores that can be fabricated by lithographic methods along with on-chip silicon-based electronic circuits and circuit techniques that amplify and isolate their various electrical signals, and (b) the exploration of a dipole sensing methodology which in principle can distinguish signals from each of the DNA bases. A quadrature capacitance sensor will be incorporated in some of the fabricated nanopores. Arrays of nanopores will be constructed on silicon substrates using a self-aligned compositional approach. Quadrature dipole moment detectors will be constructed that yield a signal independent of the rotation of the DNA molecule relative to the electrodes.

描述（由申请人提供）：今天，合成纳米孔器件作为对单个生物大分子进行高速非酶审问的有趣候选器件，受到了广泛的研究。例如，为了以高速对未知成分的单个DNA片段进行测序，就需要这种功能。虽然目前美国国立卫生研究院资助的几个小组正在研究关于大分子易位物理和新型读出方案的许多理论方面，但纳米孔在测序系统中的实际应用还需要大量的纳米孔阵列并行工作，每个纳米孔阵列都连接到高灵敏度的电子放大器/检测器。