Towards the Development of a Syndrome-specific Diagnostic Tool

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The long term goal of this project is the development of an ultrasensitive integrated platform for the antigendetection diagnosis of multiple potential bioterror agents, based on the novel technology of microfabricated retro-reflectors. It is widely accepted that most terrorist attacks are covert, and therefore the infectious agent will be unknown until the first person becomes acutely ill and seeks medical help. The availability of an instrument capable of detecting several agents simultaneously would greatly enhance our response to a possible bioterror attack because of the ability to screen patients presenting with non-specific signs and symptoms (the vast majority) or the possibility of testing based on syndromic presentation. We have demonstrated the inexpensive fabrication and very high detectability of micron-scale retroreflectors, and brightness modulation by gold nanoparticles and magnetic particles (for integration with sample preparation) in an analyte-responsive manner. A few hundred 40 nm particles, or a single 2.8 urn magnetic bead, can be reliably detected on each element of a large retroreflector array, with simple optics potentially costing less than $1000. Testing is underway with rickettsiae and with human clinical samples for Norwalk virus and other noroviruses. Very high specificity can be achieved using magnetic and/or fluid-shear removal of non-specifically bound particles, by tight control of reflector brightness uniformity, and by the use of colocated reference reflectors. We propose development of a microfluidics-based portable, user-friendly, accurate and ultrasensitive device capable of detecting multiple pathogens in parallel. Testing will initially focus on Francisella tularensis, Cryptosporidium parvum, Rift Valley fever virus, Norwalk virus, and Rickettsia rickettsii, and will coordinate with the Diagnostics Theme investigators and WRCE subject matter experts on these agents. Testing will begin in vitro with attenuated or killed agent, and progress to testing with animal and human specimens, and with virulent agents in the University of Texas Medical Branch's BSL-3 and BSL-4 facilities.