Exploring the structural and electrical properties of DNA origami nanowires is an important endeavor for the advancement of DNA nanotechnology and DNA nanoelectronics. Highly conductive DNA origami nanowires are a desirable target for creating low-cost, self-assembled, nanoelectronic devices and circuits. In this work, the structure-dependent and moisture-dependent electrical conductance of DNA origami nanowires is systematically investigated. Silicon nitride (Si3N4) on silicon semiconductor chips with gold electrodes are used for collecting electrical conductance measurements of DNA origami nanowires, which are found to be more electrically conductive on Si3N4 substrates treated with a monolayer of hexamethyldisilazane (HMDS) (~1013 ohms) than on native Si3N4 substrates without HMDS (~1014 ohms). Atomic force microscopy (AFM) measurements of the height of DNA origami nanowires on mica and Si3N4 substrates reveal that DNA origami nanowires are ~1.6 nm taller on HMDS-treated substrates than on the untreated ones indicating that the DNA origami nanowires undergo increased structural deformation when deposited onto untreated substrates, causing a decrease in electrical conductivity. Another study indicates that the same DNA origami nanowires are more electrically conductive (~1012 ohms) in ambient/humid conditions. Finally, we demonstrate that DNA origami nanowires are more electrically conductive in aqueous conditions than under dry conditions in air. These studies highlight the importance of understanding and controlling the interface conditions and environmental factors that affect the electrical conductance of DNA origami nanowires, while also revealing the potential of DNA origami nanowires to be used as sensors and electronic devices.

The behavior of charge transport in molecular scale electronics is governed by the innate chemical structure of the molecular system as well as it’s coupling to the macroscopic electrical contacts. An in depth understanding of this relationship could allow for the design of nano-electronic devices one atom at a time. Thus far, our understanding of the relationship between molecular structure and transport phenomena has been deduced through systematic studies on families of molecules with subtle variations in their chemical structure which regularly results in conflicting explanations for their underlying behavior. Thus, there is a clear and evident need for a more refined means of directly interrogating the structure of a current carry single molecule. In this work, we address this need by developing an experimental platform capable of simultaneously measuring the electrical and Raman response of a single molecule junction. This approach allows for mutually verifiable evidence of single molecule sensitivity in our measurements providing a highly reliable platform for investigating the influence of chemical structure on transport properties. By using a scanning tunneling microscope (STM) based break junction system, combined with a commercially purchased confocal Raman microscope, we are able to create single-molecule junctions between the apex of the STM tip and a conductive substrate supporting a monolayer of a target molecule and measure its conductance. Consequently, this nano-junction has a lightning rod effect when illuminated by a Raman excitation source, creating an intense and highly localized field within the junction allowing for detectable Raman scattering originating from a single molecule, thus allowing to probe the structural dynamics of a current-carrying single molecule. We then demonstrate the utility of this platform in both the field of molecule electronics as well as chemical analysis. We show that through correlations in the conductance signal and Raman scattering from the molecular junction, it is possible to directly observe structural changes in the backbone of a single molecule junction and how this affects its conductance as well as see signatures providing insight on different binding motifs. We then apply this technique to a subset of amino acids and show that, with the aid of machine learning models, it is possible to reliably identify single amino acids using both the conductance and Raman spectral information but not either independently, demonstrating the need and utility for this platform for future advances in single molecule identification.

DNA structural stability and programmability offer innumerable degrees of freedom for the design and fabrication of DNA-based devices. DNA sequences can adopt complex structures beyond the double helix, and these structures can occur either naturally or artificially. A thorough understanding of the electrical properties of these intricate structures is still lacking and investigating the charge transport in these structures is of fundamental importance for developing DNA-based electronic devices or sensing platforms. This thesis examines the electronic properties of various complex DNA structures and the possibility of electrically identifying conformational differences using the single molecule break junction (SMBJ) method. First, the conductance of an artificial DNA nanostructure, designed using DNA origami approaches, is examined. The single-molecule break junction (SMBJ) approach, which has been leveraged to examine charge transport through a variety of single-molecule devices, has been adopted to obtain the conductance of individual DNA origamis while bridging the gap between the SMBJ’s electrodes. Thermodynamic analysis and molecular dynamic simulations suggest that the DNA origami used in this study is very stable. Also, different SMBJ tapping modes show that the DNA origami is highly conductive compared to double-stranded DNA. Next, we systematically study the naturally occurring noncanonical guanine-quadruplex (G-quadruplex) structures and their transport properties by increasing the number of G-tetrads. We found that the conductance of the G-quadruplex is weakly length-dependent. These results suggest that the dominant transport mechanism is thermally activated hopping. Finally, besides the G-quadruplex’s essential regulatory role in biology, it is also the basis of many genetic diseases. Here, beyond the fundamental studies of DNA complex structures, we compare different tools for detecting G-quadruplex structures. In particular, circular dichroism (CD), gel electrophoresis, and SMBJ were used to detect the presence of G-quadruplex structures. DNA sequences in this study show that the conductance value of the G-quadruplex is one order of magnitude higher than the double-stranded DNA. Therefore, harnessing electrical signals from individual molecules may provide the ultimate detection scheme for G-quadruplex. Taken together, these experiments demonstrate that the structural polymorphism in DNA greatly influences the electronic properties, and one can foresee that complex structures will open doors to a wide variety of applications, including but not limited to molecular switches, sensors, and nanowires.

The potential role of DNA in nanoelectronics and nano sensors arises from its distinct self-assembly properties, charge transport characteristics, and significance in essential chemical and biological processes. This necessitates a comprehensive understanding of charge transport and transfer mechanisms, essential for both nano electronic applications like DNA-based memories and the utilization of DNA-based platforms as bioelectronic sensors. In our work, we initially explored the application of DNA molecules as biosensors. Using h RNA-based single-molecule conductance experiments, we successfully detected distinct variants of the SARS-CoV-2 virus. Our approach, adaptable for emerging variants, relied on a methodology to select target DNA sequences from specific variant's RNA segments. Employing single-molecule break junction (SMBJ) measurements, we achieved sensitivity and specificity in detecting RNA:DNA hybrids via their conductance. Our approach demonstrated the potential to detect SARS-CoV-2 variants, including B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta), and B.1.1.529 (Omicron). Understanding charge transport within DNA is crucial in designing sensitive and efficient DNA sensors. Previous studies have revealed that charge flow in DNA is through pi-stacking between adjacent base pairs. Yet, factors influencing this transport within DNA require further exploration. Thus, the latter part of this thesis investigates what could enhance or disrupt a charge moving across a single DNA molecule junction. We first investigated the influence of nearest neighbors within DNA sequences. Our findings reveal that the arrangement of bases in a sequence substantially impacts coupling in hopping transport, leading to significant changes in conductance values in short DNA molecules. Building on these insights, we proceed to design longer conductive DNA sequences, spanning 7 nanometers. This device length enables interactions with other biological systems such as proteins, paving the way for novel sensing applications. Next, we explored the integration of non-canonical bases to modulate energy and density of state distribution within dsDNA molecules, broadening the genetic alphabet beyond the classic Watson-Crick (GCAT) base pairs. Although these modifications alter the distribution of DOS and HOMO-LUMO energies, the molecule's conductance remains relatively unaffected. This shows the potential for expanding DNA’s electronic design while preserving its structural and electronic integrity. In the final segment of our work, we conducted temperature-dependent charge transport studies under vacuum and cryogenic condition, shedding light on the intricacies of DNA's charge transport phenomena. We measured DNA conductance using the SMBJ technique at varying temperatures from 77 K to 290 K, alongside IV characteristics. Among many models proposed for explaining DNA conductance temperature dependence our findings align with the variable range hopping model, indicating that DNA charge transport emerges as a multifaceted interplay of tunneling and hopping, resulting in intricate quantum phenomena within a single molecule. In summary, our study provides a systematic exploration of charge transport in DNA molecules and its application in biosensors. Through carefully designed sequences and SMBJ measurement techniques, we unravel conductance and current-voltage behaviors. Leveraging these insights, we not only developed DNA for COVID variant detection but also engineered highly conductive DNA sequences, thus facilitating efficient charge transport. This endeavor substantially contributes to unraveling the intricacies of DNA's charge transport and its implications for ultra-high-sensitive sensors and extended DNA wires.

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