Nanowire quantum effect devices for field effect single-molecule DNA sequencing

用于场效应单分子 DNA 测序的纳米线量子效应装置

• 批准号: 1606141
• 负责人: Walter Hu
• 金额: $ 41万
• 依托单位: University of Texas at Dallas
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-01 至 2020-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1606141&HistoricalAwards=false
• 关键词: Nanowire; quantum; effect; devices; field

PI: Wu, Walter Proposal Number: 1606141During the past decade, we have witnessed accelerated development of genome sequencing from second generation to next-generation sequencing (NGS), which is transforming the nature of biological inquiry. In particular, benefiting from the electronics industry's development, DNA sequencing technology has reduced the cost per genome to about $1000 at a rapid rate and improved accuracy. This project investigates the downward scalability of semiconductor sequencing technology towards single-molecule of DNA.The objective of this project is to investigate the scalability of field effect semiconductor DNA sequencing method to a resolution of single molecule. The key idea is to utilize serpentine nanowire (sNW) quantum effect device (QED) as a sensor for localized detection of intrinsic charge of DNA phosphate backbone during a modified Sanger sequencing process of a single DNA molecule. The sensor device is a molecular scale Si nanowire with diameter less than 10 nm defined by e-beam lithography. At this length scale, strong quantum confinement induces quantization of sub-bands and higher carrier mobility. Together with Coulomb blockade effects, the sensitivity to its surface charge can be significantly enhanced to enable single-molecule DNA sequencing. Techniques of surface hydrolysis, molecular layer deposition of linker molecule, as well as the use of HfO2 as gate dielectrics are proposed to improve surface stability and therefore signal to noise ratio of DNA sequencing. The novel serpentine NW morphology would enable fast kinetics during the DNA binding to the sensor surfaces and considerably reduce surface binding competition between nanowire and its surrounding area, without the use of difficult selective chemistry. Chips are designed to fit commercial next generation sequencing systems to take advantages of fluidic management and data acquisition capability. The successful scaling of semiconductor field effect sequencing technology to the single molecular level would have high impacts to the field of DNA sequencing. At large, this technology may ultimately allow downward scalability of sequencing time to a few hours and cost to below $100/genome. The research findings would likely contribute new knowledge to the fields of nanoelectronics, biosensing, DNA sequencing, and quantum mechanics, etc. The program will utilize existing programs, such as NSF REU and "e-Biosensor Discovery" to generate significant educational impact, including integration of research and education, promoting diversity, and outreach to K-12, the underrepresented women and Hispanic student body at University of Texas at Dallas, and local community colleges as well as the workforce in the Dallas and Fort/Worth area.

Pi：Wu，Walter提案编号：1606141在过去的十年中，我们见证了基因组测序从第二代测序到下一代测序(NGS)的加速发展，这正在改变生物研究的性质。特别是受益于电子行业的发展，DNA测序技术迅速将每个基因组的成本降低到1000美元左右，并提高了准确性。本项目研究半导体测序技术对单分子DNA的向下可伸缩性。本项目的目的是研究场效应半导体DNA测序方法对单分子分辨率的可伸缩性。其核心思想是利用蛇形纳米线(SNW)量子效应器件(QED)作为传感器，在改进的单DNA分子Sanger测序过程中定位检测DNA磷酸骨架的本征电荷。该传感器件是电子束曝光法定义的直径小于10 nm的分子尺度硅纳米线。在这个长度尺度上，强的量子限制导致了子带的量子化和更高的载流子迁移率。结合库仑阻塞效应，可以显著提高对其表面电荷的敏感性，从而实现单分子DNA测序。为了提高DNA测序的表面稳定性，从而提高DNA测序的信噪比，提出了表面水解、连接分子的分子层沉积以及使用HfO2作为栅电介质的技术。这种新颖的蛇纹状NW形态将在DNA与传感器表面结合的过程中实现快速动力学，并显著减少纳米线与其周围区域之间的表面结合竞争，而不需要使用困难的选择性化学。芯片旨在适应商业下一代测序系统，以利用流体管理和数据采集能力的优势。将半导体场效应测序技术成功地扩展到单分子水平，将对DNA测序领域产生重大影响。总体而言，这项技术最终可能会将测序时间向下扩展到几个小时，并将成本降低到每基因组100美元以下。这些研究成果可能会为纳米电子学、生物传感、DNA测序和量子力学等领域贡献新的知识。该计划将利用现有的项目，如NSF REU和“e-Biosensor Discovery”，产生重大的教育影响，包括将研究和教育相结合，促进多样性，并推广到K-12、达拉斯大学代表不足的女性和拉美裔学生群体、达拉斯和沃斯堡地区的当地社区学院和劳动力。