PORTABLE, RAPID AND USER-FRIENDLY DIAGNOSTIC SYSTEM FOR CHEMICAL THREAT EXPOSURE - DESCRIPTION (provided by applicant): Following a terrorist attack or accidental release of chemical threat agents, hundreds of potential victims may require testing and treatment. The critical need to test large numbers of people for exposure to chemical threat agents will overwhelm the capacity of the clinical and public health infrastructure. Many of the clinical and public health facilities lack the capabilities for rapid diagnosis of biomarkers indicative of specific exposures in biological samples. The ~25,000 sentinel laboratories in the Laboratory Response Network, which coordinate preparedness and response, need diagnostic tools to enable accurate decentralized testing. Rapid and portable diagnostic tools suitable for detection of chemical threat exposure and for use by emergency care providers in order to guide medical countermeasures and treatments are also in critical need by medical professionals, military forces, and first responders. The goal of the proposed project is to develop new portable diagnostic system capable of rapidly detecting metabolites of chemical threat agents in biological samples such as urine and plasma. As shown in the recent terrorist attack and police intervention in Russia, victims of an exposure to an unknown chemical could have been treated more successfully if the specific agent, or at least the class of agent, could have been determined quickly. Specially, we will address the need for identifying patients that require aggressive life-saving therapy by developing a urine test for chemical threat exposure. The test will measure the biomarkers that are indicative of specific exposure. The proposed test strip is based on binding-induced label-free fluorescent resonance energy transfer (FRET) detection. The technology employs aptamer molecular beacons specific to metabolites of chemical threat agents, as recognition elements, and fluorescent quantum dots as signal output. The proposed test strip combines the advantages of highly specific and durable aptamer receptors, nanotechnology and immunochromatographic bioassays. This novel research will result in colorimetric strips with features of rapid, autonomous, cost-effective, and easily interpretable results. The proposed colorimetric test strips will be suitable for medical professionals, military forces and first responders to rapidly diagnose and identify individuals exposed to chemical threat agents for prompt treatment. In Phase I we will demonstrate the feasibility of the test strip for detection of the major metabolites (alkyl methylphosphonic acid) of nerve gas reagents, and in Phase II we will develop strip panels capable of assaying multiple biomarkers indicative of specific exposure in a single measurement of patient's biological sample to meet the requirement of a diagnostic system during large causality. Human exposure to chemical threat agents may lead to disease or dysfunction, and mass casualty. This proposed research seeks to develop wearable diagnostic strips capable of assaying biomakers indicative of specific exposures in biological samples.
