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.
The proposed work will result in the development of a new, ultrasensitive diagnostic technology and its integration into a platform device capable of rapidly detecting multiple pathogens in clinical specimens. The low cost, low operating cost, portability, and multiplexing capability of the device will support routine, syndrome-based multiagent diagnostic assays at the point-of-care.
|Paterson, Andrew S; Raja, Balakrishnan; Garvey, Gavin et al. (2014) Persistent luminescence strontium aluminate nanoparticles as reporters in lateral flow assays. Anal Chem 86:9481-8|
|Santiago, Felix W; Covaleda, Lina M; Sanchez-Aparicio, Maria T et al. (2014) Hijacking of RIG-I signaling proteins into virus-induced cytoplasmic structures correlates with the inhibition of type I interferon responses. J Virol 88:4572-85|
|Pflughoeft, Kathryn J; Swick, Michelle C; Engler, David A et al. (2014) Modulation of the Bacillus anthracis secretome by the immune inhibitor A1 protease. J Bacteriol 196:424-35|
|Lavinder, Jason J; Wine, Yariv; Giesecke, Claudia et al. (2014) Identification and characterization of the constituent human serum antibodies elicited by vaccination. Proc Natl Acad Sci U S A 111:2259-64|
|Valbuena, Gustavo; Halliday, Hailey; Borisevich, Viktoriya et al. (2014) A human lung xenograft mouse model of Nipah virus infection. PLoS Pathog 10:e1004063|
|Nieves, Wildaliz; Petersen, Hailey; Judy, Barbara M et al. (2014) A Burkholderia pseudomallei outer membrane vesicle vaccine provides protection against lethal sepsis. Clin Vaccine Immunol 21:747-54|
|Gardner, Christina L; Hritz, Jozef; Sun, Chengqun et al. (2014) Deliberate attenuation of chikungunya virus by adaptation to heparan sulfate-dependent infectivity: a model for rational arboviral vaccine design. PLoS Negl Trop Dis 8:e2719|
|Litvinov, Julia; Hagström, Anna E V; Lopez, Yubitza et al. (2014) Ultrasensitive immuno-detection using viral nanoparticles with modular assembly using genetically-directed biotinylation. Biotechnol Lett 36:1863-8|
|Caro-Gomez, Erika; Gazi, Michal; Goez, Yenny et al. (2014) Discovery of novel cross-protective Rickettsia prowazekii T-cell antigens using a combined reverse vaccinology and in vivo screening approach. Vaccine 32:4968-76|
|Georgiou, George; Ippolito, Gregory C; Beausang, John et al. (2014) The promise and challenge of high-throughput sequencing of the antibody repertoire. Nat Biotechnol 32:158-68|
Showing the most recent 10 out of 303 publications