BME PhD Dissertation Defense: Amish Patel

Title: “Synthesis and Imaging of Near-infrared I and II Quantum Dot Heterostructures”

Advisory Committee: Allison M. Dennis, PhD – NEU ChemE (Research Advisor) Darren Roblyer, PhD – BME (Chair) Chen Yang, PhD – ECE Hadi T. Nia, PhD – BME Michelle Teplensky, PhD – BME

Abstract: Quantum dots (QDs) are remarkable optically active nanomaterials that present excellent brightness and photostability, emission wavelength tunability, and versatile functional groups in near-infrared (NIR) fluorescence imaging. These qualities have enabled preclinical imaging of anatomical features and therapeutic delivery. However, there remains an ongoing need for more powerful QD contrast agents with improved chemical and optical stability, tunability within the NIR-I (700-900 nm) and NIR-II (1000-1700 nm) biological imaging windows, and simpler synthesis methods. I present innovations to the synthesis and imaging of QDs to improve their accessibility and utility in NIR biological imaging. First, I design a scalable synthesis for inverted indium phosphide QDs emitting in the NIR-I bioimaging window by utilizing stable, non-pyrophoric indium phosphide clusters acting as single source precursors. Careful study of cluster reactivity allows for production of thick indium phosphide shells while limiting nucleation-based side reactions. Second, I develop biostable, NIR-II lead-sulfide quantum dots by adding a zinc sulfide shell layer through multiple synthesis variations. The zinc sulfide shell maintains QD optical stability in harsh, lysosomal-like environments. Lastly, I improve the dynamic range of a preclinical imager outfitted with an InGaAs camera to enhance imaging of our bright, NIR-II-emitting QDs in small animal models. I modify classical high dynamic range (HDR) imaging methods by accounting for exposure time-dependent InGaAs camera noise with dynamic denoising and pixel weighting range adjustment. This HDR imaging workflow produces quantitatively accurate radiance maps without worry of sensor saturation from high local fluorophore concentrations, such as in the liver or spleen.