Hemorrhagic fever viruses such as Ebola, Marburg and Lassa are responsible for current endemic diseases in Africa and are classified as Category A biothreats by the CDC because of the high fatality that can be associated with these diseases and their low infectious dose. Because of the concern of the release of weaponized Ebola, Marburg or Lassa, simple and effective detection and diagnostics are essential. While there are several existing assays for diagnosing infection with these viruses, they involve significant biosafety considerations, as the assays are not closed system sample-to-answer systems. This reduces the ability of these assays to be used in routine clinical testing and point-of-care settings. We propose to investigate the potential for nanophotonics technologies as rapid and multiplexed detection systems to diagnose infection with hemorrhagic fever viruses. We have chosen two technologies, pioneered by Boston University researchers, photonic nanohole arrays and interferometric reflectance imaging as our primary detection platforms. We will develop both technologies initially in a competitive manner. Both technologies have shown promise in their ability to show multiplexed detection of different antigens and pathogens. Based on the specific criteria of sensitivity (<104 PFu/ml) and specificity, we will select the most promising technology (or a complementary combination) for development of an integrated sample-to-answer prototype detector. The prototype detector will be an integrated system that will incorporate microfluidics, a multiplexed detector with the capacity to distinguish Ebola, Marburg, and Lassa infection. The system will be designed to initiate diagnosis from serum, and provide a closed-system sample-to-answer diagnostic that is rapid and easy to use. This system will serve as a proof of concept system to drive the development of photonic technologies as portable diagnostics. Photonics systems have the advantage of being rapid, label-free systems with an established record of miniaturization and inexpensive manufacture. Thus, these technologies provide an important avenue of exploration for new portable devices. To accomplish these goals we have assembled a multidisciplinary team with complementary expertise. To facilitate the development of the detector technology itself, the team includes experts in microfluidics, nanohole array development, and interferometric detection. To drive the testing and capture probe development technology, the team includes experts in pseudotype development to allow BSL2-testing and animal model experts familiar with all of the VHF viruses that will be analyzed. Prototyping will be facilitated through collaboration with Becton Dickinson, a company with significant experience in the development of virus diagnostics. Based on the strength of the team that we have assembled, we believe that we are well positioned to properly investigate the potential for nanophotonics systems as low power diagnostics that are simple and have a straightforward path to miniaturization and application in both clinical and point-of-care in resource limited settings.

Public Health Relevance

The goal of this proposal is to develop a proof-of-concept design for a self-contained diagnostic system for viruses that cause hemorrhagic fever. The basis for the diagnostic platform will be a light-based detector that will allow low-power, simple testing of patients that are potentially infected. The straightforward technology that is proposed here can be directly scaled to inexpensive large-scale production through the leveraging of existing telecommunications and computing manufacturing techniques.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI096159-03
Application #
8511558
Study Section
Special Emphasis Panel (ZAI1-BLG-M (M1))
Program Officer
Repik, Patricia M
Project Start
2011-08-01
Project End
2016-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
3
Fiscal Year
2013
Total Cost
$836,193
Indirect Cost
$160,399
Name
Boston University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Speranza, Emily; Bixler, Sandra L; Altamura, Louis A et al. (2018) A conserved transcriptional response to intranasal Ebola virus exposure in nonhuman primates prior to onset of fever. Sci Transl Med 10:
Schultz, Michaela J; Frydman, Horacio M; Connor, John H (2018) Dual Insect specific virus infection limits Arbovirus replication in Aedes mosquito cells. Virology 518:406-413
Ünlü, Nese Lortlar; Kanik, Fulya Ekiz; Seymour, Elif et al. (2017) DNA-Directed Antibody Immobilization for Robust Protein Microarrays: Application to Single Particle Detection 'DNA-Directed Antibody Immobilization. Methods Mol Biol 1571:187-206
Scherr, Steven M; Freedman, David S; Agans, Krystle N et al. (2017) Disposable cartridge platform for rapid detection of viral hemorrhagic fever viruses. Lab Chip 17:917-925
Carter, Erik P; Seymour, Elif Ç; Scherr, Steven M et al. (2017) Visualizing Ebolavirus Particles Using Single-Particle Interferometric Reflectance Imaging Sensor (SP-IRIS). Methods Mol Biol 1628:259-270
Trueb, Jacob; Avci, Oguzhan; Sevenler, Derin et al. (2017) Robust Visualization and Discrimination of Nanoparticles by Interferometric Imaging. IEEE J Sel Top Quantum Electron 23:
Ruedas, John B; Connor, John H (2017) Generating Recombinant Vesicular Stomatitis Viruses for Use as Vaccine Platforms. Methods Mol Biol 1581:203-222
Wilson, Michael R; Fedewa, Greg; Stenglein, Mark D et al. (2016) Multiplexed Metagenomic Deep Sequencing To Analyze the Composition of High-Priority Pathogen Reagents. mSystems 1:
Fawcett, Helen; Ünlü, M Selim; Connor, John H (2016) New Approaches for Virus Detection through Multidisciplinary Partnerships. ACS Infect Dis 2:378-81
Scherr, Steven M; Daaboul, George G; Trueb, Jacob et al. (2016) Real-Time Capture and Visualization of Individual Viruses in Complex Media. ACS Nano 10:2827-33

Showing the most recent 10 out of 18 publications