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Tailored magnetic nanoparticles for in vitro, in vivo and in situ magnetorelaxometry


The development of novel methods of probing biological interactions is critical to the advancement of biomedical science. Recent progress in the synthesis and science of nanoscale structures has engendered a renaissance in the evolution of techniques aimed at the analysis of these interactions. The use of nanomaterials provides the researcher with access to the extended quantum behaviors of these materials and the ability to intimately interact with the fundamental subunits of biology. Magnetic materials on this size scale, such as magnetic nanoparticles (MNPs), also exhibit unique properties not available in larger structures and have likewise become of chief interest in the field of nanotechnology. Through exploitation of various synthesis techniques and parameters, the physicochemical and magnetic properties of magnetic nanoparticles can be exquisitely controlled. Magnetorelaxometry is the field of study concerned with the mechanisms of magnetic relaxation and the development of applications that capitalize upon these phenomena. The preferred instrument for the analysis of these magnetic properties is the superconducting quantum interference device (SQUID). This work focuses on the development and chemical modification of MNPs for use with this instrument and the demonstration of novel magnetorelaxometric applications in biomedicine. The basic chemical synthesis of magnetic nanoparticles is first developed and demonstrated, after which the SQUID system and the magnetic properties of a library of synthesis products are analyzed and evaluated for use in magnetorelaxometry. An in vitro assay for sepsis diagnostics is then developed based upon the conjugation of anti-Escherichia coli O157: H7 antibodies to magnetic nanoparticles and the magnetorelaxometric quantification of binding of these MNPs to the target pathogen in buffer, serum and blood. Next, parameters for the conjugation of insecticidic crystal proteins to MNPs are developed and optimized for an in vivo assay for the quantification of toxin binding in the gut of live Caenorhibditis elegans nematodes. Lastly, the concentration dependent effects of MNPs upon PC12 cells are evaluated; followed by the development of an antibody based in situ assay for the detection of tubulin using the TAT peptide for entry into live cells. The results of these assays underscore the utility of magnetorelaxometry for applications in biomedicine

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