Browsing by Subject "Contrast agent"
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Item Biomedical photoacoustics beyond thermal expansion : photoacoustic nanoDroplets(2012-05) Wilson, Katheryne Elizabeth; Emelianov, Stanislav Y.; Fowlkes, Brian; Hamilton, Mark; Sokolov, Konstantin; Williams, RobertThe recent increase in survival rates of most cancers is due to early detection greatly aided by medical imaging modalities. Combined ultrasound and photoacoustic imaging provide both morphological and functional/molecular information which can help to detect and diagnose cancer in its earliest stages. However, both modalities can benefit from the use of contrast agents. The objective of this thesis was to design, synthesize, and test a nano-sized, dual contrast agent for combined ultrasound and photoacoustic imaging named Photoacoustic nanoDroplets. This agent consists of liquid perfluorocarbon nanodroplets with encapsulated plasmonic nanoparticles. These dual contrast agents utilize optically triggered vaporization for photoacoustic signal generation, providing significantly higher signal amplitude than that from the traditionally used mechanism, thermal expansion. Upon pulsed laser irradiation, liquid perfluorocarbon undergoes a liquid-to-gas phase transition generating giant photoacoustic transients from these dwarf nanoparticles. Once triggered, the gaseous phase provides ultrasound contrast enhancement. Demonstrated in this work are the design, synthesis, characterization, and testing of Photoacoustic nanoDroplets in phantom and animal studies, and preliminary work into adapting these agents into targeted, drug delivery vehicles for simultaneous detection, diagnosis, and treatment of diseases.Item Controlled assembly of biodegradable gold nanoclusters for in vivo imaging(2015-12) Stover, Robert John; Johnston, Keith P., 1955-; Truskett, Thomas M; Fan, Donglei; Korgel, Brian; Sokolov, KonstantinGold nanoparticles are of interest in biomedical imaging applications due to their inert nature and ability to exhibit surface plasmon resonance. These phenomena can result in high near-infrared extinction (NIR) due to asymmetry or close interparticle spacings within gold structures, making these materials ideal for photoacoustic imaging. Using this imaging modality, these materials allow for high contrast compared to the body’s tissues which exhibit a transparent “window” between 700-1100 nm, making them perfect for early cancer detection. However many gold structures designed for this application fail to achieve high NIR-absorbance at the <5 nm sizes which are required for efficient kidney clearance. Therefore, we designed a system which assembles ~4 nm primary gold particles into closely-spaced clusters of controlled size using a biodegradable, weakly adsorbing polymer and balance of colloidal attractive and repulsive forces. Thus, when the polymer degrades in acidic environments – such as within cells – the residual charge on the primary particles leads to dissociation of the clusters back to renal-clearable constituents. Since proteins in the blood and cells can increase the diameter of the primary particles above the 5 nm threshold, nanoparticle surfaces were designed to have a mixture of charged and zwitterionic molecules to limit protein interactions through buried charges and increased particle hydration. Strongly-bound, zwitterionic thiol-containing ligands were also investigated to resist the intracellular exchange of biomolecules which could compromise the clearable nature of the particles. These decorated nanoparticles were then assembled into clusters through one of two methods which varied either gold and polymer concentrations through evaporation, or particle charge via electrolyte addition prior to quenching by dilution in DI water. Once assembled, clusters assembled with polymer showed dissociation behavior after incubation in pH 5 acidic solutions to mimic the cellular pH environment. In other cases, sintering of the gold nanoparticle clusters prevented such dissociation. This thesis demonstrates the ability to not only create biocompatible nanoparticle surfaces, but to establish control size control over nanocluster assemblies which are capable of being used as NIR contrast agents.Item Nanoscale characterization of interactions between molecular specific plasmonic nanoparticles and living cells and its implications for optical imaging of protein-protein interactions(2009-12) Harrison, Nathan Daniel; Sokolov, Konstantin V. (Associate professor); Keto, John; Fink, Manfred; Florin, Ernst-Ludwig; Richards-Kortum, RebeccaImaging of biomolecules on the nano-scale is a crucial developing technology with major implications for our understanding of biological systems and for detection and therapy of disease. Plasmonic nanoparticles are a key optical contrast agent whose signal is generated by the collective oscillation of electrons in the metal particle. The resonance behavior of the electrons depends strongly on the arrangement of neighboring nanoparticles in a structure. This property may be exploited in imaging applications to report information on nanoscale morphology of targeted biomolecules. While the effect of plasmon resonance coupling has been studied in dimers and linear arrays of nanoparticles, this phenomenon remains largely unexplored in the case of 2D and 3D assemblies which are important in molecular cell imaging. This dissertation demonstrates how the optical signal from assemblies of gold nanoparticles can be related to nanoscale morphology in cellular imaging systems. First, the scattering spectra from live cells labeled with gold nanoparticles were collected and compared to the nanoscale arrangement of the particles in the same cells as determined by electron micrograph. Then, trends in scattering spectra with respect to nanoparticle arrangement were analyzed using a model system that allowed precise control over arrangement of nanoparticles. Several approaches to creating these model systems are discussed including biochemical linking, capillary assembly of colloidal particles, and direct deposition of gold onto substrates patterned by electron beam lithography. Spectral properties of the assemblies including peak position, width, and intensity are gathered and related to model variables including interparticle gap and overall particle number. It is shown that the redshift in the scattering spectra from nanoparticle assemblies is derived from both the particle number and the gap and is due to near-field coupling of particles as well as phase retardation of the scattered wave. The redshift behavior saturates as the number of particles in the aggregate increases but the saturation point depends strongly on interparticle gap. The drastic dependence of the red-shift saturation on the gap between nanoparticles has not been previously described; this phenomenon can have significant impact on the development of nanoparticle contrast agents and plasmonic sensor arrays.