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<p>The refractive index sensitivity of plasmonic nanoparticles is utilized in the
development of real-time, label-free biodetection. Analyte molecules that bind to
receptor-conjugated nanoparticles cause an increase in local refractive index that
in turn induces an energy shift in the optical resonance of the particle. Biomolecular
binding is quantified by quantitatively measuring these resonance shifts. This work
describes the application and optimization of a biomolecular detection system based
on gold nanorods as an optical transducer.</p>
<p>A microspectroscopy system was developed to collect scattering spectra of single
nanoparticles, and measure shifts of the spectra as a function of biomolecular binding.
The measurement uncertainty of LSPR peak shifts of the system was demonstrated to
be 0.3 nm. An analytical model was also developed that provides the optimal gold
nanorod geometry for detection with specified receptor-analyte pair. The model was
applied to the model biotin-streptavidin system, which resulted in sensing system
with a detection limit of 130 pM - an improvement by four orders of magnitude over
any other single-particle biodetection previously presented in the literature.</p>
<p>Alternative optical detection schemes were also investigated that could facilitate
mulitplexed biosensing. A theoretical model was built to investigate the efficacy
of using a multi-channel detector analogous to a conventional RGB camera. The results
of the model indicated that even in the best case, the detection capabilities of such
a system did not provide advantages over the microspectroscopic approach.</p>
<p>We presented a novel hyperspectral detection scheme we term Dual-Order Spectral
Imaging (DOSI) which is capable of simultaneously measuring spectra of up to 160
individual regions within a microscope's field of view. This technique was applied
to measuring shifts of individual nanoparticles and was found to have a peak measurement
uncertainty of 1.29 nm, at a measurement rate of 2-5 Hz.</p>
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