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

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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.