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.
|School:||Arizona State University|
|School Location:||United States -- Arizona|
|Source:||DAI-B 71/01, Dissertation Abstracts International|
|Keywords:||DNA sequencing, Single molecule conductance, Tunneling|
Copyright in each Dissertation and Thesis is retained by the author. All Rights Reserved
The supplemental file or files you are about to download were provided to ProQuest by the author as part of a
dissertation or thesis. The supplemental files are provided "AS IS" without warranty. ProQuest is not responsible for the
content, format or impact on the supplemental file(s) on our system. in some cases, the file type may be unknown or
may be a .exe file. We recommend caution as you open such files.
Copyright of the original materials contained in the supplemental file is retained by the author and your access to the
supplemental files is subject to the ProQuest Terms and Conditions of use.
Depending on the size of the file(s) you are downloading, the system may take some time to download them. Please be