Dissertation/Thesis Abstract

The proof of concept for a novel approach to DNA sequencing
by Lin, Lisha, Ph.D., Arizona State University, 2009, 87; 3392130
Abstract (Summary)

This dissertation presents work on a novel approach to DNA sequencing, Sequencing By Recognition (SBR). SBR is based on the chemical recognition of DNA bases via enhanced electrical current when Watson-Crick hydrogen bonded base pairs form between a base-functionalized probe and a base on a DNA to be read. One important aspect of this method is to prove that it is possible to tunnel across a DNA molecule.

Tunneling currents that can identify different bases are detected via hydrogen bonds facilitated transport when the immobilized guanidinium grabs the phosphate group connected to a base that forms Watson-Crick bonds with the closest complementary base attached to the other electrode. Using Scanning Tunneling Microscope (STM), results show that electrode-tethered guanidinium ions form hydrogen bonds which enable the transverse tunneling through native DNA. Bases were identified with a high accuracy via current-distance measurements in hydrogen-bonded tunnel junctions between bases and nucleosides.

However, the limited resolution of the present approach makes it unsuitable for DNA sequencing applications where single-base resolution is required. Thus another "telegraph noise" method was developed to measure the tunnel conductance of single hydrogen bonded pair. Experiments results determined the absolute tunnel conductance for adenine-thymidine, 2-amino-8mercaptoadenine-thymidine and guanine-deoxythymidine spanning gold electrodes. The distributions of switching times clearly allow identification of both H-bond and molecule-metal contact breaking. According to all the preliminary results, shorter tunneling path is required to obtain higher gap conductance so as to make SBR method become possible.

Indexing (document details)
School: Arizona State University
School Location: United States -- Arizona
Source: DAI-B 71/01, Dissertation Abstracts International
Subjects: Biophysics
Keywords: DNA sequencing, Single molecule conductance, Tunneling
Publication Number: 3392130
ISBN: 978-1-109-57567-5
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