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Towards Single-Molecule Nanopore DNA and Protein Sequencing

Abstract

Precise determination of DNA and protein sequences is essential to understanding biological systems. After more than 30 years of development, nanopore technology has been demonstrated to be capable of real-time long-read sequencing of single DNA molecules. However, current nanopore DNA sequencing is still limited by low consensus accuracy due to systematic error in reading homopolymers and other sequences with similar levels of ionic blockage. While nanopore DNA sequencing technology is revolutionizing genomics research, whether an analogous nanopore technology can be used to identify and sequence protein molecules remains largely unexplored. In the first part of this dissertation, I investigated the feasibility of ultraacurate nanopore DNA sequencing based on experimental sequencing data and computational modeling. In the second part of the dissertation, I investigated the theoretical feasibility of protein identification and sequencing using nanopore technologies. I also presented experimental work on the development of an integrated opto-electrical system for nanopore fabrication process and its potential application in single-molecule protein identification using high-speed optical detection.

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