Size and shape specific particles toward biomedical imaging: design, fabrication, and characterization
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The power of a biomedical imaging modality can be augmented and is, in large part, determined by the capabilities of the available contrast agents. For example, quantum dots represent a colorful palette of powerful contrast agents for optical fluorescence imaging and Raman spectroscopy, given their tunable multiplexing capability and long-term stability compared to traditional organic molecule-based fluorescent labels. On the contrary, as the workhorses in both clinical and research imaging, the full potentials of magnetic resonance imaging and computed tomography have yet to be actualized due to several existing fundamental limitations in the currently available contrast agents, including but not limited to, the lack of multiplexing capability, low sensitivity, as well as the lack of functional imaging capacity. Leveraging both traditional top-down micro- and nanoelectromechanical systems fabrication techniques and bottom-up self-assembly approaches, this dissertation explores the possibility of mitigating these limitations by engineering precisely controllable, size and shape (as well as a host of other materials properties) specific micro- and nanoparticles, for use as the next generation contrast agents for magnetic resonance imaging and computed tomography. Herein, the ways by which engineering approaches can impact the design, fabrication and characterization of contrast agents is investigated. Specifically, different configmations of magnetic micro- and nanoparticles, including double-disk and hollow-cylinder structmes, fabricated using a top-down approach were employed as magnetic resonance imaging contrast agents enabled with a multiplexing capability and improved sensitivity. Subsequently, a scalable nanomanufactming platform, utilizing nanoporous anodized aluminum oxide membranes as templates for pattern transfer as well as thermal/ultraviolet nanoimprinting techniques, was developed for the high throughput fabrication of size and shape specific polymeric nanorods. When ladened with X-ray attenuating tantalum oxide nanoparticle payloads, these polymeric nanorods can be used as contrast agents for computed tomography, yielding prolonged vascular circulation times, improved sensitivity, as well as targeted imaging capabilities. Furthermore, by applying various payload materials, this nanomanufacturing platform also has the flexibility to produce contrast agents for other imaging modalities, as well as the potential to realize dual-purpose agents for both diagnostic and therapeutic applications.
Thesis (Ph.D.)--Boston University