Intracellular Detection of Small Molecules in Live Cells

ABSTRACT: The extreme toxicity of organophosphate (OP) chemical warfare agents (CWA) is due to their specific, rapid, and irreversible reaction with cholinesterase enzymes. A significant portion of this reactive nature of OP agents is directly due to the unique metabolically active environment found in and around cells. The goal of this proposal is to harness this unique intracellular environment to create a new class of highly sensitive, robust, and field portable sensor for rapidly detecting military personnel exposure to OP CWAs. In its final configuration, the proposed nanoparticles could be delivered as intradermal tattoos, allowing for rapid and personalized detection of potentially toxic OP agents. In Phase I, Agave BioSystems, in collaboration with Dr. Carl Batt of Cornell University, proposes to develop a warfare agent (CWA) detection system by incorporating fluorescent dyes demonstrated to sense CWAs into biocompatible nanoparticles that will serve as the support for the dye and the site of the response. The ability of these dye-impregnated nanoparticles to detect the presence of organophosphate CWAs will be tested in human cells. The goal is to create a system that utilizes human cellular chemistry to aid in the detection of potential CWA exposure. BENEFIT: In addition to detecting organophosphates, these types of nanoparticle sensors will have applications beyond CWAs since the nanoparticles are capable of supporting dyes capable of sensing myriad of other toxicants biomolecules. The potential diagnostic markets for this approach extend to VOC and other toxic industrial chemical detection in homeland security, law enforcement and industrial hygiene settings. The nanoparticles-based sensors could also be adapted for the detection of lactate, glucose, hydration, and corticosteroids levels.