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Major Research Project RP004

Collaborating Institution: University of Houston, Houston, TX

Principal Investigator: Richard Willson, PhD

Title of the Project: Towards the Development of a Syndrome-specific Diagnostic Tool

Co-Investigators:

Expected Product: Development of a new, ultrasensitive diagnostic technology and its integration into a platform device capable of rapidly detecting multiple pathogens in clinical specimens.

Description: The long-term goal of this project is the development of an ultrasensitive, integrated platform for the antigen detection 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 μm magnetic bead, can be reliably detected on each element of a large retroreflector array, with simple optics potentially costing less than $1000. Planarization improved mass transfer and flow-force specificity enhancement, but introduced physisorption issues which now are largely resolved. A new linear layout greatly increased the “sensitive” fraction of the array, increasing sensitivity, and automated image analysis is now highly successful.

We recently also have demonstrated the micro-lithographic fabrication of freely-suspended retroreflector cubes, which may serve as the basis of a simple, few-agent point-of-care diagnostic device.

In response to external reviews, we have shifted emphasis to agents for which infected human samples are realistically available. Specifically, we will deemphasize Francisella tularensis, Cryptosporidium parvum, and Rift Valley fever virus, and focus on dengue virus and intracellular bacterial pathogens, especially Ehrlichia chaffeensis. A promising simple assay using suspended retroreflector cubes will focus on Norwalk virus.

Testing 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.