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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54AI057156-10
Application #
8440798
Study Section
Special Emphasis Panel (ZAI1-DDS-M)
Project Start
Project End
2015-02-28
Budget Start
2013-03-01
Budget End
2015-02-28
Support Year
10
Fiscal Year
2013
Total Cost
$556,837
Indirect Cost
$82,299
Name
University of Texas Medical Br Galveston
Department
Type
DUNS #
800771149
City
Galveston
State
TX
Country
United States
Zip Code
77555
Navarro, Juan-Carlos; Giambalvo, Dileyvic; Hernandez, Rosa et al. (2016) Isolation of Madre de Dios Virus (Orthobunyavirus; Bunyaviridae), an Oropouche Virus Species Reassortant, from a Monkey in Venezuela. Am J Trop Med Hyg 95:328-38
Park, Arnold; Yun, Tatyana; Hill, Terence E et al. (2016) Optimized P2A for reporter gene insertion into Nipah virus results in efficient ribosomal skipping and wild-type lethality. J Gen Virol 97:839-43
Aghazadeh, Amirali; Lin, Adam Y; Sheikh, Mona A et al. (2016) Universal microbial diagnostics using random DNA probes. Sci Adv 2:e1600025
Inglis, Fiona M; Lee, Kim M; Chiu, Kevin B et al. (2016) Neuropathogenesis of Chikungunya infection: astrogliosis and innate immune activation. J Neurovirol 22:140-8
Hatcher, Christopher L; Mott, Tiffany M; Muruato, Laura A et al. (2016) Burkholderia mallei CLH001 Attenuated Vaccine Strain Is Immunogenic and Protects against Acute Respiratory Glanders. Infect Immun 84:2345-54
Chen, Hui; Hagström, Anna E V; Kim, Jinsu et al. (2016) Flotation Immunoassay: Masking the Signal from Free Reporters in Sandwich Immunoassays. Sci Rep 6:24297
Crannell, Zachary Austin; Cabada, Miguel Mauricio; Castellanos-Gonzalez, Alejandro et al. (2015) Recombinase polymerase amplification-based assay to diagnose Giardia in stool samples. Am J Trop Med Hyg 92:583-7
Walker, David H; Dumler, J Stephen (2015) The role of CD8 T lymphocytes in rickettsial infections. Semin Immunopathol 37:289-99
Mott, Tiffany M; Vijayakumar, Sudhamathi; Sbrana, Elena et al. (2015) Characterization of the Burkholderia mallei tonB Mutant and Its Potential as a Backbone Strain for Vaccine Development. PLoS Negl Trop Dis 9:e0003863
Gregory, Anthony E; Judy, Barbara M; Qazi, Omar et al. (2015) A gold nanoparticle-linked glycoconjugate vaccine against Burkholderia mallei. Nanomedicine 11:447-56

Showing the most recent 10 out of 362 publications