| dc.description.abstract |
<p>Noble metal nanoparticles exhibit unique optical properties that are beneficial
to a variety of applications, including molecular imaging. The large scattering cross
sections of nanoparticles provide high contrast necessary for biomarkers. Unlike alternative
contrast agents, nanoparticles provide refractive index sensitivity revealing information
regarding the local cellular environment. Altering the shape and composition of the
nanoparticle shifts the peak resonant wavelength of scattered light, allowing for
implementation of multiple spectrally distinct tags. In this project, nanoparticles
that scatter in different spectral windows are functionalized with various antibodies
recognizing extra-cellular receptors integral to cancer progression. A hyperspectral
imaging system is developed, allowing for visualization and spectral characterization
of cells labeled with these conjugates. Various molecular imaging and microspectroscopy
applications of plasmonic nanoparticles are then investigated. First, anti-EGFR gold
nanospheres are shown to quantitatively measure receptor expression with similar performance
to fluorescence assays. Second, anti-EGFR gold nanorods and novel anti-IGF-1R silver
nanospheres are implemented to indicate local cellular refractive indices. Third,
because biosensing capabilities of nanoparticle tags may be limited by plasmonic coupling,
polarization mapping is investigated as a method to discern these effects. Fourth,
plasmonic coupling is tested to monitor HER-2 dimerization. Experiments reveal the
interparticle conformation of proximal HER-2 bound labels, required for plasmonic
coupling-enhanced dielectric sensing. Fifth, all three functionalized plasmonic tags
are implemented simultaneously to indicate clinically relevant cell immunophenotype
information and changes in the cellular dielectric environment. Finally, flow cytometry
experiments are conducted utilizing the anti-EGFR nanorod tag to demonstrate profiling
of receptor expression distribution and potential increased multiplexing capability.</p>
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