| Quantum dots (QDs) are inorganic nanoparticles that have exceptional optical properties. Currently, QDs have failed to reach their potential as fluorescent probes in live cells, due to the nontrivial requirements for biological interfacing. The goal of this thesis is to address technical hurdles related to the reproducible synthesis of QDs, strategies for the specific targeting of QDs to biological cells and to understanding and exploitation of the photophysical properties. High quality QDs of varying composition (CdSe, CdTe and core/shell CdSe/ZnS) were synthesized with an organometallic method. To prepare biocompatible QDs, three strategies were used. The simplest strategy used small mercaptocarboxylic acids, while performance improvements were realized with engineered-peptide and lipid-micelle coatings. For specific biological targeting of the QDs, conjugation strategies were devised to attach biomolecules, while spectroscopic characterization methods were developed to assess conjugation efficiencies. To target gram-negative bacterial cells, an electrostatic self-assembly method was used to attach an antibiotic selective for this class of bacteria, polymyxin B. To target dopamine neurotransmitter receptor, a covalent conjugation method was used to attach dopamine, the endogenous ligand for that receptor. It was shown that dopamine molecule enabled electron transfer to QDs and the photophysics was studied in detail. A novel conjugation and targeting strategy was explored to enable the selective binding of QDs to polyhistidine epitopes on membrane proteins. Epifluorescence microscopy was used to evaluate the biological activity of the three QD probes. Combined, they add to the QD 'toolkit' for live-cell imaging. Finally, due to its negative implications in biological imaging, the fluorescent intermittency (blinking) of CdTe QDs was investigated. It was shown that mercaptocarboxylic acids contribute to the blinking suppression of the QDs, results that may aid in the design of nonblinking QDs. Overall, these findings should be useful in the future design of QDs for biological imaging and biosensing applications. |
