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- red blood cells; fluorescence spectroscopy; blood analyte monitoring; encapsulation; NIR dyes; zinc oxide; gas sensing; photobleaching
thesis / dissertation description
Development of sensors for detection of various chemical and biological species is an important and ever-growing field. In particular, optical-based sensors enable a remote, rapid method for continuous or on-demand monitoring. Monitoring humidity is important across many applications, such as humidity control within moisture-sensitive environments and in medical, semiconductor, and food science fields. Following a study of photobleaching, defect-related emission of zinc oxide nanoparticles was monitored as a function of relative humidity. An important next step is its application to monitoring toxic gases, as air pollution has been identified as a major health concern. Of importance for the biomedical field is monitoring key blood analytes for human health. Monitoring blood pH is critical for specific patient groups, such as those suffering from diabetic ketoacidosis and congenital lactic acidosis. A pH-sensitive fluorophore was loaded within red blood cells for use as a continuous blood analyte monitor. Future work will focus on glucose, as current estimates show that one out of every three children born in 2000 will develop diabetes in his or her lifetime ? thus, the global impact of this disease is immense. Results from ZnO studies indicate that photobleaching is related to the surface area to volume ratio. ZnO nanoparticles display a linear response to humidity with a sensitivity of 0.008417 RH^-1 and 0.01898 RH^-1 for nitrogen and air environments, respectively. Owing to reversibility and high sensitivity, ZnO nanoparticles have great potential as optical-based environmental sensors. Results from dye-loaded ghost studies indicate that fluorescence intensity of intracellular dyes report on extracellular pH. Resealed ghosts loaded with a fluorescein isothiocyanate-glycylglycine conjugate reversibly track pH with a resolution down to 0.014 pH unit. For use in vivo, the development of an NIR pH-sensitive dye was paramount. Unfortunately, all NIR dyes tested exhibited poor pH sensitivity while displaying sensitivity to external factors (e.g., temperature, concentration, proteins). However, circulation kinetics of resealed ghosts were easily monitored once injected in vivo with an optical fiber-based system. Although the cells were rapidly removed from circulation, the loaded ghosts resulted in higher signal than would be expected for free dye alone. Once optimized, the resealed ghosts could serve as a long-term, continuous, circulating biosensor for the management of diseases.