Signal transduction with hybridization chain reactions

Some of the most exciting developments in the field of nucleic acid engineering include the utilization of synthetic nucleic acid molecular devices as gene regulators, as disease marker detectors, and most recently, as therapeutic agents. The common thread between these technologies is their reliance on the detection of specific nucleic acid input markers to generate some desirable output, such as a change in the copy number of an mRNA (for gene regulation), a change in the emitted light intensity (for some diagnostics), and a change in cell state within an organism (for therapeutics). The research presented in this thesis likewise focuses on engineering molecular tools that detect specific nucleic acid inputs, and respond with useful outputs.

Four contributions to the field of nucleic acid engineering are presented: (1) the construction of a single nucleotide polymorphism (SNP) detector based on the mechanism of hybridization chain reaction (HCR); (2) the utilization of a single-stranded oligonucleotide molecular Scavenger as a means of enhancing HCR selectivity; (3) the implementation of Quenched HCR, a technique that facilitates transduction of a nucleic acid chemical input into an optical (light) output, and (4) the engineering of conditional probes that function as sequence transducers, receiving target signal as input and providing a sequence of choice as output. These programmable molecular systems are conceptually well-suited for performing wash-free, highly selective rapid genotyping and expression profiling in vitro, in situ, and potentially in living cells.

Chain-forming zintl antimonides as novel thermoelectric materials

Zintl phases, a subset of intermetallic compounds characterized by covalently-bonded "sub-structures," surrounded by highly electropositive cations, exhibit precisely the characteristics desired for thermoelectric applications. The requirement that Zintl compounds satisfy the valence of anions through the formation of covalent substructures leads to many unique, complex crystal structures. Such complexity often leads to exceptionally low lattice thermal conductivity due to the containment of heat in low velocity optical modes in the phonon dispersion. To date, excellent thermoelectric properties have been demonstrated in several Zintl compounds. However, compared with the large number of known Zintl phases, very few have been investigated as thermoelectric materials.

From this pool of uninvestigated compounds, we selected a class of Zintl antimonides that share a common structural motif: anionic moieties resembling infinite chains of linked MSb₄ tetrahedra, where $M$ is a triel element. The compounds discussed in this thesis (A₅M₂Sb₆ and A₃MSb₃, where A = Ca or Sr and M = Al, Ga and In) crystallize as four distinct, but closely related "chain-forming" structure types. This thesis describes the thermoelectric characterization and optimization of these phases, and explores the influence of their chemistry and structure on the thermal and electronic transport properties. Due to their large unit cells, each compound exhibits exceptionally low lattice thermal conductivity (0.4 - 0.6 W/mK at 1000 K), approaching the predicted glassy minimum at high temperatures. A combination of Density Functional calculations and classical transport models were used to explain the experimentally observed electronic transport properties of each compound. Consistent with the Zintl electron counting formalism, A₅M₂Sb₆ and A₃MSb₃ phases were found to have filled valence bands and exhibit intrinsic electronic properties. Doping with divalent transition metals (Zn²⁺ and Mn²⁺) on the M³⁺ site, or Na¹⁺ on the A³⁺ site allowed for rational control of the carrier concentration and a transition towards degenerate semiconducting behavior. In optimally-doped samples, promising peak zT values between 0.4 and 0.9 were obtained, highlighting the value of continued investigations of complex Zintl phases.