BME PhD Proposal Seminar: Supriya Ravichandran
Development and Characterization of Novel Agents to Detect Nanomaterials in Biological Systems
Professor Lisa DeLouise, Ph.D., M.P.D.
The presence of nanoparticles (NPs) in commercial day-to-day use products has led to concerns regarding human health and safety due to occupational and unintentional exposure. The fate of nanomaterials in biological systems depends on their ability to breech epithelial barriers and their systemic translocation, which depends in part on the NP physiochemical properties and tissue barrier status. The diversity of NPs in terms of their size, surface chemistry and charge poses a challenge for detection in biological systems. Widely used techniques such as fluorescence microscopy and TEM to detect NPs in tissues have their own limitations, as they cannot achieve nanoscale resolution to adequately distinguish particles from cellular structures. This brings about a knowledge gap in determining exact localization of low levels of NPs that maybe present in vivo due to long-term chronic NP exposure. Although a considerable amount of literature investigating NP tissue penetration exists, experimental limitations and the wide variety of analytical techniques used contribute to considerable inconsistencies in the results reported. Our goal is to develop a set of NProbes which are NP-binding proteins using phage display to allow the detection of sparse NPs in tissues, commonly rendered undetectable by other techniques. The NProbes will function similar to antibodies, and will bind NPs with high specificity dictated by NP properties such as size, surface chemistry, agglomeration state and charge, thereby allowing their detection using immunohistochemistry. The reagents will thus serve as diagnostic tools to aid in the detection of both fluorescent and non-fluorescent NPs that maybe present in low levels, using commonly used microscopic techniques in biological systems. NProbes will be validated ex vivo using a human skin model and in vivo using a mouse model.