ASU Electronic Theses and Dissertations
This collection includes most of the ASU Theses and Dissertations from 2011 to present. ASU Theses and Dissertations are available in downloadable PDF format; however, a small percentage of items are under embargo. Information about the dissertations/theses includes degree information, committee members, an abstract, supporting data or media.
In addition to the electronic theses found in the ASU Digital Repository, ASU Theses and Dissertations can be found in the ASU Library Catalog.
Dissertations and Theses granted by Arizona State University are archived and made available through a joint effort of the ASU Graduate College and the ASU Libraries. For more information or questions about this collection contact or visit the Digital Repository ETD Library Guide or contact the ASU Graduate College at gradformat@asu.edu.
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Description
Charge transport in molecular systems, including DNA (Deoxyribonucleic acid), is involved in many basic chemical and biological processes. Studying their charge transport properties can help developing DNA based electronic devices with many tunable functionalities. This thesis investigates the electric properties of double-stranded DNA, DNA G-quadruplex and dsDNA with modified base.
First, double-stranded DNA with alternating GC sequence and stacked GC sequence were measured with respect to length. The resistance of DNA sequences increases linearly with length, indicating a hopping transport mechanism. However, for DNA sequences with stacked GC, a periodic oscillation is superimposed on the linear length dependence, indicating a partial coherent transport. The result is supported by the finding of delocalization of the highest occupied molecular orbitals of Guanines from theoretical simulation and by fitting based on the Büttiker’s theory.
Then, a DNA G4-duplex structures with a G-quadruplex as the core and DNA duplexes as the arms were studied. Similar conductance values were observed by varying the linker positions, thus a charge splitter is developed. The conductance of the DNA G-tetrads structures was found to be sensitive to the π-stacking at the interface between the G-quadruplex and DNA duplexes by observing a higher conductance value when one duplex was removed and a polyethylene glycol (PEG) linker was added into the interface. This was further supported by molecular dynamic simulations.
Finally, a double-stranded DNA with one of the bases replaced by an anthraquinone group was studied via electrochemical STM break junction technique. Anthraquinone can be reversibly switched into the oxidized state or reduced state, to give a low conductance or high conductance respectively. Furthermore, the thermodynamics and kinetics properties of the switching were systematically studied. Theoretical simulation shows that the difference between the two states is due to a difference in the energy alignment with neighboring Guanine bases.
First, double-stranded DNA with alternating GC sequence and stacked GC sequence were measured with respect to length. The resistance of DNA sequences increases linearly with length, indicating a hopping transport mechanism. However, for DNA sequences with stacked GC, a periodic oscillation is superimposed on the linear length dependence, indicating a partial coherent transport. The result is supported by the finding of delocalization of the highest occupied molecular orbitals of Guanines from theoretical simulation and by fitting based on the Büttiker’s theory.
Then, a DNA G4-duplex structures with a G-quadruplex as the core and DNA duplexes as the arms were studied. Similar conductance values were observed by varying the linker positions, thus a charge splitter is developed. The conductance of the DNA G-tetrads structures was found to be sensitive to the π-stacking at the interface between the G-quadruplex and DNA duplexes by observing a higher conductance value when one duplex was removed and a polyethylene glycol (PEG) linker was added into the interface. This was further supported by molecular dynamic simulations.
Finally, a double-stranded DNA with one of the bases replaced by an anthraquinone group was studied via electrochemical STM break junction technique. Anthraquinone can be reversibly switched into the oxidized state or reduced state, to give a low conductance or high conductance respectively. Furthermore, the thermodynamics and kinetics properties of the switching were systematically studied. Theoretical simulation shows that the difference between the two states is due to a difference in the energy alignment with neighboring Guanine bases.
ContributorsXiang, Liming (Author) / Tao, Nongjian (Thesis advisor) / Lindsay, Stuart (Committee member) / Gould, Ian (Committee member) / Arizona State University (Publisher)
Created2016
Description
Cell adhesion is an important aspect of many biological processes. The atomic force microscope (AFM) has made it possible to quantify the forces involved in cellular adhesion using a technique called single cell force spectroscopy (SCFS). AFM based SCFS offers versatile control over experimental conditions for probing directly the interaction between specific cell types and specific proteins, surfaces, or other cells. Transmembrane integrins are the primary proteins involved in cellular adhesion to the extra cellular matix (ECM). One of the chief integrins involved in the adhesion of leukocyte cells is αMβ2 (Mac-1). The experiments in this dissertation quantify the adhesion of Mac-1 expressing human embryonic kidney (HEK Mac-1), platelets, and neutrophils cells on substrates with different concentrations of fibrinogen and on fibrin gels and multi-layered fibrinogen coated fibrin gels. It was shown that multi-layered fibrinogen reduces the adhesion force of these cells considerably. A novel method was developed as part of this research combining total internal reflection microscopy (TIRFM) with SCFS allowing for optical microscopy of HEK Mac-1 cells interacting with bovine serum albumin (BSA) coated glass after interacting with multi-layered fibrinogen. HEK Mac-1 cells are able to remove fibrinogen molecules from the multi-layered fibrinogen matrix. An analysis methodology for quantifying the kinetic parameters of integrin-ligand interactions from SCFS experiments is proposed, and the kinetic parameters of the Mac-1 fibrinogen bond are quantified. Additional SCFS experiments quantify the adhesion of macrophages and HEK Mac-1 cells on functionalized glass surfaces and normal glass surfaces. Both cell types show highest adhesion on a novel functionalized glass surface that was prepared to induce macrophage fusion. These experiments demonstrate the versatility of AFM based SCFS, and how it can be applied to address many questions in cellular biology offering quantitative insights.
ContributorsChristenson, Wayne B (Author) / Ros, Robert (Thesis advisor) / Beckstein, Oliver (Committee member) / Lindsay, Stuart (Committee member) / Ugarova, Tatiana (Committee member) / Arizona State University (Publisher)
Created2016
Description
Emerging pathogens present several challenges to medical diagnostics. Primarily, the exponential spread of a novel pathogen through naïve populations require a rapid and overwhelming diagnostic response at the site of outbreak. While point-of-care (PoC) platforms have been developed for detection of antigens, serologic responses, and pathogenic genomes, only nucleic acid diagnostics currently have the potential to be developed and manufactured within weeks of an outbreak owing to the speed of next-generation sequencing and custom DNA synthesis. Among nucleic acid diagnostics, isothermal amplification strategies are uniquely suited for PoC implementation due to their simple instrumentation and lack of thermocycling requirement. Unfortunately, isothermal strategies are currently prone to spurious nonspecific amplification, hindering their specificity and necessitating extensive empirical design pipelines that are both time and resource intensive. In this work, isothermal amplification strategies are extensively compared for their feasibility of implementation in outbreak response scenarios. One such technology, Loop-mediated Amplification (LAMP), is identified as having high-potential for rapid development and PoC deployment. Various approaches to abrogating nonspecific amplification are described including a novel in silico design tool based on coarse-grained simulation of interactions between thermophilic DNA polymerase and DNA strands in isothermal reaction conditions. Nonspecific amplification is shown to be due to stabilization of primer secondary structures by high concentrations of Bst DNA polymerase and a mechanism of micro-complement-mediated cross-priming is demonstrated as causal via nanopore sequencing of nonspecific reaction products. The resulting computational model predicts primer set background in 64% of 67 test assays and its usefulness is illustrated further by determining problematic primers in a West Nile Virus-specific LAMP primer set and optimizing primer 3’ nucleotides to eliminate micro-complements within the reaction, resulting in inhibition of background accumulation. Finally, the emergence of Orthopox monkeypox (MPXV) as a recurring threat is discussed and SimCycle is utilized to develop a novel technique for clade-specific discrimination of MPXV based on bridging viral genomic rearrangements (Bridging LAMP). Bridging LAMP is implemented in a 4-plex microfluidic format and demonstrates 100% sensitivity in detection of 100 copies of viral lysates and 45 crude MPXV-positive patient samples collected during the 2022 Clade IIb outbreak.
ContributorsKnappenberger, Mark Daniel (Author) / Anderson, Karen S (Thesis advisor) / LaBaer, Joshua (Committee member) / Roberson, Robert (Committee member) / Lindsay, Stuart (Committee member) / Arizona State University (Publisher)
Created2023
Description
Understanding the interplay between the electrical and mechanical properties of single molecules is of fundamental importance for molecular electronics. The sensitivity of charge transport to mechanical fluctuations is a key problem in developing long lasting molecular devices. Furthermore, harnessing this response to mechanical perturbation, molecular devices which can be mechanically gated can be developed. This thesis demonstrates three examples of the unique electromechanical properties of single molecules.
First, the electromechanical properties of 1,4-benzenedithiol molecular junctions are investigate. Counterintuitively, the conductance of this molecule is found to increase by more than an order of magnitude when stretched. This conductance increase is found to be reversible when the molecular junction is compressed. The current-voltage, conductance-voltage and inelastic electron tunneling spectroscopy characteristics are used to attribute the conductance increase to a strain-induced shift in the frontier molecular orbital relative to the electrode Fermi level, leading to resonant enhancement in the conductance.
Next, the effect of stretching-induced structural changes on charge transport in DNA molecules is studied. The conductance of single DNA molecules with lengths varying from 6 to 26 base pairs is measured and found to follow a hopping transport mechanism. The conductance of DNA molecules is highly sensitive to mechanical stretching, showing an abrupt decrease in conductance at surprisingly short stretching distances, with weak dependence on DNA length. This abrupt conductance decrease is attributed to force-induced breaking of hydrogen bonds in the base pairs at the end of the DNA sequence.
Finally, the effect of small mechanical modulation of the base separation on DNA conductance is investigated. The sensitivity of conductance to mechanical modulation is studied for molecules of different sequence and length. Sequences with purine-purine stacking are found to be more responsive to modulation than purine-pyrimidine sequences. This sensitivity is attributed to the perturbation of &pi-&pi stacking interactions and resulting effects on the activation energy and electronic coupling for the end base pairs.
First, the electromechanical properties of 1,4-benzenedithiol molecular junctions are investigate. Counterintuitively, the conductance of this molecule is found to increase by more than an order of magnitude when stretched. This conductance increase is found to be reversible when the molecular junction is compressed. The current-voltage, conductance-voltage and inelastic electron tunneling spectroscopy characteristics are used to attribute the conductance increase to a strain-induced shift in the frontier molecular orbital relative to the electrode Fermi level, leading to resonant enhancement in the conductance.
Next, the effect of stretching-induced structural changes on charge transport in DNA molecules is studied. The conductance of single DNA molecules with lengths varying from 6 to 26 base pairs is measured and found to follow a hopping transport mechanism. The conductance of DNA molecules is highly sensitive to mechanical stretching, showing an abrupt decrease in conductance at surprisingly short stretching distances, with weak dependence on DNA length. This abrupt conductance decrease is attributed to force-induced breaking of hydrogen bonds in the base pairs at the end of the DNA sequence.
Finally, the effect of small mechanical modulation of the base separation on DNA conductance is investigated. The sensitivity of conductance to mechanical modulation is studied for molecules of different sequence and length. Sequences with purine-purine stacking are found to be more responsive to modulation than purine-pyrimidine sequences. This sensitivity is attributed to the perturbation of &pi-&pi stacking interactions and resulting effects on the activation energy and electronic coupling for the end base pairs.
ContributorsBruot, Christopher, 1986- (Author) / Tao, Nongjian (Thesis advisor) / Lindsay, Stuart (Committee member) / Mujica, Vladimiro (Committee member) / Ferry, David (Committee member) / Arizona State University (Publisher)
Created2014