Point-of-care (POC) diagnostics are easy-to-use, low-cost devices that can rapidly detect a biomarker of interest without the need for highly trained personnel or expensive equipment. In resource-limited settings, POC testing is often the only viable option for patients, which highlights the importance of developing sensitive technologies for early disease detection and monitoring of treatment methods. Hydrogels are flexible 3D structures made with crosslinked hydrophilic components that absorb large amounts of water. These systems are sensitive to different chemical or physical stimuli, and the magnitude of their response is usually directly proportional to the magnitude of the applied external stimuli. In the diagnostics field, hydrogels are mostly being used for enzyme detection and immunodiagnostics. For these applications, the biomarker acts as a signal that triggers a volume, color, or state change of the hydrogel, an example of the latter being a gel-sol transition or vice versa. This technology often requires the chemical modification of at least one of the main hydrogel components so that the system is specific towards the molecule of interest. Accordingly, these devices need to be manufactured in a laboratory setting with complex equipment and often expensive reagents, and they also require personnel with extensive knowledge and experience to conduct the assay and its analysis. Thus, it would be desirable to design a hydrogel system that is responsive to the presence of the biomarker of interest without the need for chemical modification of the reagents to design a robust, POC-friendly device that can be manufactured in all parts of the world. To develop this system, we focused on calcium alginate dextran hydrogels beads for the detection of abnormal concentrations of ions, such as bicarbonate and phosphate, in patient samples. This system can be synthesized by a simple ionic crosslinking method based solely on the complexation of the oppositely charged species, i.e., alginate and calcium, which comprise the gel matrix. For disease detection, we took advantage of a calcium depletion mechanism based on the reaction of the biomarkers of interest with the divalent calcium cation in the calcium alginate gel matrix. The timeframe for hydrogel degradation was therefore correlated with the sample’s ion concentration, making our POC device semi-quantitative. To our knowledge, this is the first demonstration of the use of nonionic polymers to improve the morphology of calcium alginate hydrogel beads using a simple processing method that involves minimal labor, equipment, and reagents. The simplified bead synthesis protocol combined with a user-friendly device that we developed allows for the rapid detection of high serum bicarbonate or urine phosphate levels at the POC.

Gonadotropin-releasing hormone (GnRH) is a primary and essential regulator of vertebrate reproduction. When GnRH neurons are compromised, GnRH expression is attenuated, producing the condition Idiopathic Hypogonadotropic Hypogonadism (IHH). IHH is characterized by infertility and/or delayed or absent puberty. When this condition is accompanied by anosmia, it is termed Kallmann syndrome. Although it is clearly a crucial factor in the reproduction of mammalian species, little is known about the genetic regulators of GnRH neuronal ontogeny. In the work presented herein, we elucidate developmental and genetic mechanisms that control the migration and maturation of GnRH neurons, and therefore illuminate the novel mechanisms responsible for IHH. Furthermore, we have identified new genes influencing the relationship between nasal development and GnRH neuron migration- further elucidating the etiology of Kallmann syndrome. The two genes that are explored in the work presented here are the closely related homeodomain transcription factors, sine oculis-related homeobox 3 (Six3) and Six6. First, we present data demonstrating that Six3 regulates GnRH neuron migration through actions external to the GnRH neuron. Six3 heterozygous mice displayed disrupted migration of GnRH neurons and severe olfactory impairment. Interestingly when the role of Six3 specifically within the GnRH neuron was investigated using a GnRH specific cre-recombinase, we found that Six3 acts within the neuron to upregulate GnRH neuron number. In addition, we investigated the actions of the closely related gene Six6. Six6 was found to be essential for survival of GnRH neurons and maintenance of fertility in a Six6 knock-out mouse. Six6 was found to play a similar role within the GnRH neuron in enabling fertility; however, within the GnRH neuron, Six6 acts to regulate GnRH expression. These investigations have enabled us to garner knowledge concerning the novel regulatory mechanisms of this fascinating hormone; and, has allowed us to shed light on the causes of infertility plaguing ~7% of all couples.

Soft materials are a diverse and rich field of interest. Materials which form structure by their own self-assembly are of special interest. New material properties can be achieved by the self-assembly of constituent soft matter. Two soft matter systems are investigated in this dissertation from different perspectives. An in silico approach is applied to explore semiflexible polymers; X-ray scattering is applied to probe QD-LC composites.

Semiflexible polymers can generate a range of filamentous networks significantly different in structure from those seen in conventional polymer solutions. Our coarse-grained simulations with an implicit cross-linker potential show that networks of branching bundles, knotted morphologies, and structural chirality can be generated by a generalized approach independent of specific cross-linkers. Network structure depends primarily on filament flexibility and separation, with significant connectivity increase after percolation. Results should guide the design of engineered semiflexible polymers.

Thermotropic liquid crystal provides an active basis for organization of nanoparticles. Using a bottom-up approach, nanoparticles well dispersed in the isotropic phase can be self-assembled by exclusion from the nematic phase as the material cools from the isotropic phase. A ligand exchange reaction can be used to create nanoparticles with mesogenic ligand coatings to allow better dispersion and assemble novel structures. Small angle X-ray scattering is used to inform the structure of a variety of materials which apply this design concept. These metamaterials have tunable properties with applications in quantum dot based electro-optic devices and more.

In their recent paper, Muir et al. (Science, 2015, 348, 1135-1138) demonstrate that the maximum depths of staghorn coral assemblages are shallower at higher latitudes, a trend that correlates with winter light levels. Based on these findings, the authors hypothesize that light availability limits the current latitudinal extent of the group and will constrain future range expansion. Here we reanalyze their data and show that depth-latitude relationships vary substantially among species, and that most species show either no significant pattern or the opposite pattern. In so doing, our reanalysis highlights a common misinterpretation of mixed-effects models: the fallacy of the average. Our findings are also consistent with fossil and contemporary observations of coral range-shifts. The factors that limit the current range extent of corals remain elusive, but they are likely species-specific and will require much further research to elucidate.