The long term goal of this project is the development of an ultrasensitive integrated platform for the antigendetectiondiagnosis of multiple potential bioterror agents, based on the novel technology of microfabricatedretro-reflectors. It is widely accepted that most terrorist attacks are covert, and therefore the infectious agentwill be unknown until the first person becomes acutely ill and seeks medical help. The availability of aninstrument capable of detecting several agents simultaneously would greatly enhance our response to apossible bioterror attack because of the ability to screen patients presenting with non-specific signs andsymptoms (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 samplepreparation) in an analyte-responsive manner. A few hundred 40 nm particles, or a single 2.8 urn magneticbead, can be reliably detected on each element of a large retroreflector array, with simple optics potentiallycosting less than $1000. Testing is underway with rickettsiae and with human clinical samples for Norwalkvirus and other noroviruses. Very high specificity can be achieved using magnetic and/or fluid-shear removalof non-specifically bound particles, by tight control of reflector brightness uniformity, and by the use of colocatedreference reflectors.We propose development of a microfluidics-based portable, user-friendly, accurate and ultrasensitive devicecapable 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 coordinatewith the Diagnostics Theme investigators and WRCE subject matter experts on these agents. Testing willbegin in vitro with attenuated or killed agent, and progress to testing with animal and human specimens, andwith virulent agents in the University of Texas Medical Branch's BSL-3 and BSL-4 facilities.
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