DNA Sequencing with Nanopores and Transverse Tunneling

该计划的目的是研究纳米电极纳米孔DNA测序装置结合混合方法，该方法测量装置对短杂交DNA序列的电响应。 其智力价值在于研究一种新的DNA测序方法，该方法具有强大的理论基础，但需要通过实验进行开发。 拟议的研究将测试完善的假设，即DNA可以通过横向隧道测量进行测序。 第一个假设是横向隧穿对特定核苷酸敏感，并且可以在纳米电极隧穿装置中检测核苷酸序列。 第二种假设通过使用与DNA杂交的短探针来放松对单碱基分辨率的需要。 提出这些标记的链引起纳米孔装置中的隧穿电流的显著波动。 更广泛的影响是发现一种新型的低成本DNA测序设备，使新的医疗应用造福大众。 成功发现用于DNA测序的低成本纳米器件将极大地扩展我们研究、诊断和治疗疾病的能力，从而为个性化基因组学带来变革。 这项研究的成功结果将通过促进广泛的DNA测序技术对全球医疗保健产生巨大影响。 这项研究还将促进与公众的外联，以传播有关基因组测序技术的潜在好处和道德风险的信息。 其他更广泛的影响包括对研究生和本科生教育的影响以及对高中生，包括代表性不足的群体的暑期外联活动的影响。

The objective of this program is to investigate nanoelectrode nanopore DNA sequencing devices combined with a hybrid approach that measures the electrical response of the devices to short hybridized DNA sequences. The intellectual merit is to investigate a new approach to DNA sequencing that has a strong theoretical basis but needs to be developed experimentally. The proposed research will test well-developed hypotheses that DNA can be sequenced by transverse tunneling measurements. The first hypothesis is that transverse tunneling is sensitive to specific nucleotides and that sequences of nucleotides can be detected in nanoelectrode tunneling devices. The second hypothesis relaxes the need for single base resolution by using short probes that hybridize with DNA. These labeled strands are proposed to give rise to significant fluctuations of the tunneling current in nanopore devices. The broader impacts are to discover a new type of low cost DNA sequencing device that enables new medical applications for the benefit of the general public. The successful discovery of low cost nanodevices for DNA sequencing would be transformative for personalized genomics by greatly expanding our ability to study, diagnose, and treat disease. A successful outcome of the research will have a tremendous impact on healthcare world-wide by facilitating wide-spread DNA sequencing technology. The research will also foster outreach to the general public to disseminate information about the potential benefits and ethical risks of genome sequencing technology. Other broader impacts include impacts on graduate and undergraduate education and summer outreach activities to high school students, including underrepresented groups.