Electronic Sequencing in Nanopores

纳米孔中的电子测序

基本信息

批准号：
7898057
负责人：
DANIEL none BRANTON
金额：
$ 74.52万
依托单位：
HARVARD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-13 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7898057
关键词：
Accounting Achievement Advanced Development Anodes Binding Carbon Carbon Nanotubes Cells Chemicals Computer software Confidential Information DNA DNA Probes DNA Sequence Data Devices Diagnosis Disclosure Disease Ecology Electrodes Electronics Environment Evolution Figs - dietary Freedom Funding Future Generations Genome Genomics Goals Government Grant Health Heart Hour Housing Human Human Genetics Investments Knowledge Label Legal patent Length Membrane Modeling Molecular Motion Nanotechnology Nanotubes National Human Genome Research Institute Nucleotides Operative Surgical Procedures Pattern Procedures Property Reading Research Proposals Route Services Side Signal Transduction Silicon Single-Stranded DNA Slide Solutions Structure Surface System Thick Time United States United States National Institutes of Health Vision Water Work base cost design detector disorder prevention electrical property experience improved instrument interest mammalian genome nanopore nanoscale programs remediation research and development research study response sensor silicon nitride single molecule single walled carbon nanotube solid state sound voltage

项目摘要

DESCRIPTION (provided by applicant): The long-term objective is a nanopore detector chip for a general utility instrument capable of inexpensive de novo sequencing that can also be used for re-sequencing projects. The instrument directly generates base-dependent electronic signals as multi-kilobase length fragments of single stranded genomic DNA is driven sequentially through nanopores articulated with electrically contacted single walled carbon nanotube probes. The final system is intended to provide a relatively high quality sequence from =6.5-fold coverage of a genome using DNA from fewer than 1 million cells, with no amplification or labeling. The specific aims are: 1) Characterize ungapped nanotube articulated nanopore detectors in ionic solution with and without DNA molecules to establish a device model; 2) Control ssDNA binding, translocation, and sliding on the nanotube surface exposed in ungapped nanotube articulated nanopores; 3) Study and optimize DNA molecule induced field effect modulation of nanotube electrode conductance in ungapped nanotube articulated nanopores as a function of nanotube bias, gate voltage, and solution properties; 4) Analyze and optimize tunneling current modulations between gapped nanotube electrodes in the first generation detector; 5) Design and fabricate a second generation detector with embedded 'T' nanotube geometry and achieve 1 Kb/sec sequencing on Kb length strands of DNA; 6) Design a third generation nanopore detector for high throughput 10 Kb/sec/nanopore sequencing. If we are able to resolve each base as it passes through a nanopore at the rate of 104 bases/sec as proposed here, an instrument with an array of 100 such nanopores could produce a high quality draft sequence of one mammalian genome in ~20 hours at a cost of approximately $1,000/mammalian genome. Genomic sequencing at these reduced costs would make vital contributions to improved human health on many fronts, including the understanding, diagnosis, treatment, and prevention of disease; environmental science and remediation; and the genetics of human health and disease derived from the understanding of evolution. PROJECT HEALTH RELEVANCE We are developing the core detector of an instrument that could produce a high-quality draft sequence of one mammalian genome in ~20 hours at a cost of approximately $1,000/mammalian genome. Genomic sequencing at these reduced costs would make vital contributions to improved human health on many fronts, including the understanding, diagnosis, treatment, and prevention of disease; environmental science and remediation; and the genetics of human health and disease derived from the understanding of evolution.

描述（由申请人提供）：长期目标是一种纳米孔检测器芯片，用于能够廉价的从头测序的通用仪器，也可以用于重新续签项目。该仪器直接生成基础依赖性电子信号，因为单链基因组DNA的多吉尔酶长度片段被依次通过用电接触的单壁碳纳米管探针表达的纳米孔驱动。最终系统旨在使用少于100万个细胞的DNA提供相对较高的质量序列，而没有扩增或标记。具体目的是：1）表征没有DNA分子和不具有DNA分子的离子溶液中未媒体的纳米管铰接式纳米孔检测器来建立设备模型； 2）控制ssDNA的结合，易位和滑动在未封闭的纳米管铰接式纳米孔中暴露的纳米管表面上； 3）研究并优化了未模拟的纳米管铰接式纳米孔中纳米管电极电导电极电导率的现场效应调制，这是纳米管偏置，栅极电压和溶液特性的函数； 4）分析和优化第一代检测器中含量纳米管电极之间的隧道电流调制； 5）用嵌入的“ T”纳米管几何形状设计和制造第二代探测器，并在DNA的Kb长度链上实现1 kb/sec的测序； 6）设计第三代纳米孔检测器，用于高吞吐量10 kb/sec/纳米孔测序。如果我们能够以这里提出的104个碱基/秒的速度通过纳米孔时解决每个碱基，那么这种纳米孔的数组可能会在20小时内以大约20小时的成本产生一个高质量的纳米孔序列，以大约1,000美元/哺乳动物的基因组产生一个高质量的草稿序列。以这些降低的成本进行基因组测序将对改善许多方面的人类健康做出至关重要的贡献，包括对疾病的理解，诊断，治疗和预防；环境科学和补救；人类健康和疾病的遗传学源于对进化的理解。项目健康相关性我们正在开发一种仪器的核心探测器，该仪器可以在约20小时内产生一个哺乳动物基因组的高质量草稿序列，成本约为1,000美元/哺乳动物的基因组。以这些降低的成本进行基因组测序将对改善许多方面的人类健康做出至关重要的贡献，包括对疾病的理解，诊断，治疗和预防；环境科学和补救；人类健康和疾病的遗传学源于对进化的理解。