Highly infectious diseases originating from bacterial (e.g., anthrax) or viral (e.g. Ebola) pathogens with high mortality rates pose high risks, includin epidemic outbreaks and hostile acts using these pathogens as biological weapons. The ability to detect and respond rapidly at the """"""""point of care"""""""" is essential for dealing with these threats. Despite increased research activity, there is currently no established point-of-care system for these pathogens due to the shortcomings of the current detection approaches, including lack of speed (culture), lack of accuracy (antigen tests), and lack of simplicity (polymerase chain reaction (PCR), in large part due to the need to amplify the genetic target material). Our long-term goal is to develop point-of-care biomedical devices using optofluidics - the combination of integrated optics and microfluidics on a single chip-scale system. The objective of this application is to demonstrate and validate a Hybrid, Integrated Molecular Analysis System (HIMAS) that is suitable for differential point-of-care diagnosis of category A pathogens. Our central hypothesis is that this can be accomplished by combining two powerful microfluidic and optical technologies that are optimized for sample processing and amplification-free detection in separate chip layers. During the initial R21 phase, our objectives will be accomplished by the following specific aims: (1) Introduce a new spectral target multiplexing approach using interferometric waveguide structures;(2) Introduce a new hybrid optofluidic system composed of a glass microfluidic layer and a silicon optical layer;(3) Validate the platform for differential diagnostics of hemorrhagic fever viruses using clinical samples. In a subsequent R33 phase, we will build on these innovations by developing a portable prototype system that can rapidly distinguish between 14 weaponizable hemorrhagic fever viruses without the need for target amplification, starting from a whole blood patient sample. The innovative contributions of the proposed approach are: (i) interferometric excitation using multi-mode interferometer (MMI) waveguides for spectral, spatial, and combinatorial target multiplexing;(ii) introduction of a new planar optofluidic system with layers optimized individually for sample processing and amplification-free nucleic acid analysis. The proposed work is significant because it overcomes the critical barriers to developing a point-of-care system for PCR-free, differential diagnostics o biodefense pathogens and other viral and bacterial threats to human health.

Public Health Relevance

This application describes a novel approach to detecting and identifying viruses rapidly and quantitatively on a compact, portable platform suitable for point-of-care diagnostics. The proposed optofluidic platform would impact public health in a number of ways, including screening for outbreaks of biodefense and emerging pathogens, rapid decision making in patient diagnosis, or continuing viral load monitoring for disease management. This new molecular diagnostic technology will contribute to understanding and treatment of infectious diseases and is broadly applicable to other areas of a developing personalized medicine in accordance with the mission of the NIH and the NIAID.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZAI1-ESB-M (J2))
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Repik, Patricia M
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University of California Santa Cruz
Schools of Engineering
Santa Cruz
United States
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Du, Ke; Park, Myeongkee; Griffiths, Anthony et al. (2017) Microfluidic System for Detection of Viral RNA in Blood Using a Barcode Fluorescence Reporter and a Photocleavable Capture Probe. Anal Chem 89:12433-12440
Du, K; Cai, H; Park, M et al. (2017) Multiplexed efficient on-chip sample preparation and sensitive amplification-free detection of Ebola virus. Biosens Bioelectron 91:489-496
Ozcelik, Damla; Stott, Matthew A; Parks, Joshua W et al. (2016) Signal-to-noise Enhancement in Optical Detection of Single Viruses with Multi-spot Excitation. IEEE J Sel Top Quantum Electron 22:
Parks, J W; Wall, T A; Cai, H et al. (2016) Enhancement of ARROW Photonic Device Performance via Thermal Annealing of PECVD-based SiO2 Waveguides. IEEE J Sel Top Quantum Electron 22:
Cai, H; Parks, J W; Wall, T A et al. (2015) Optofluidic analysis system for amplification-free, direct detection of Ebola infection. Sci Rep 5:14494
Leake, Kaelyn D; Olson, Michael A B; Ozcelik, Damla et al. (2015) Spectrally reconfigurable integrated multi-spot particle trap. Opt Lett 40:5435-8
Ozcelik, Damla; Parks, Joshua W; Wall, Thomas A et al. (2015) Optofluidic wavelength division multiplexing for single-virus detection. Proc Natl Acad Sci U S A 112:12933-7
Parks, J W; Olson, M A; Kim, J et al. (2014) Integration of programmable microfluidics and on-chip fluorescence detection for biosensing applications. Biomicrofluidics 8:054111
Parks, Joshua W; Cai, Hong; Zempoaltecatl, Lynnell et al. (2013) Hybrid optofluidic integration. Lab Chip 13:4118-23