Diagnostic approaches providing identification of viruses directly from bio-fluids with improved figures of merit (fast, accurate (selective, sensitive), simple, low power, and cost-effective) are needed. A new, innovative micro-fluidic strategy that can contribute to this goal is presented here. The system can rapidly and selectively separate, isolate and concentrate viruses from bio-fluids for direct identification or further assessments (immuno- or geno-recognition). The strategy is based on DC insulator gradient dielectrophoresis (DC-iGDEP) which provides not only the advantage of truly unique and non-linear separation of bioparticles, but also can remove unwanted components that are often present in complex biological samples and interfere with subsequent assays. The approach can fuse location to identification via electric field manipulation of bio-particles, thus avoiding a number of issues with current methods that require prior molecular recognition elements and commonly cold-chain reagents. The basis for the approach is a combination of dielectrophoretic and electro-kinetic forces in a single channel. The long-term objective is to integrate DC-iGDEP into a simple, cost effective, reliable biosensor that will be a component of a diagnostic platform that can be used in the clinical laboratory and ideally, amenable for surveillance and diagnosis in developing countries. As poof-of-concept, we will use dengue viruses as the target model for a blood borne virus and two respiratory viruses, human coronavirus OC43 and influenza that are typically only present in respiratory secretions and not in blood during acute infections. Dengue viruses are one of the most significant emerging infectious pathogens today and newly emerged corona viruses and influenza strains remain as important health concerns, thus the test samples will have """"""""real world"""""""" relevance. Standard virological assays, including virus titer, hemagglutination (HA) and inhibition (HAI), RT-PCR, and other well established serological diagnostic methods will be used in parallel with the platform development to monitor sensitivity, accuracy and overall feasibility of DC-iGDEP. The goal is to isolate/concentrate/separate virus particles from typical venipuncture and respiratory sample volumes. Once developed, the approach can be modified for a broad range of medically important viruses.

Public Health Relevance

Developing an ability to isolate and concentrate viruses from biofluids (saliva, CSF, blood) using gradient dielectrophoresis. This can be developed into devices which can detect virus at earlier phases of infection providing for better care and reduced spread of infectious agents.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Research Grants (R03)
Project #
1R03AI094193-01A1
Application #
8244067
Study Section
Special Emphasis Panel (ZRG1-IDM-V (12))
Program Officer
Park, Eun-Chung
Project Start
2012-02-07
Project End
2014-01-31
Budget Start
2012-02-07
Budget End
2013-01-31
Support Year
1
Fiscal Year
2012
Total Cost
$69,437
Indirect Cost
$19,437
Name
Arizona State University-Tempe Campus
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
943360412
City
Tempe
State
AZ
Country
United States
Zip Code
85287
Crowther, Claire V; Hayes, Mark A (2017) Refinement of insulator-based dielectrophoresis. Analyst 142:1608-1618
Ding, Jie; Lawrence, Robert M; Jones, Paul V et al. (2016) Concentration of Sindbis virus with optimized gradient insulator-based dielectrophoresis. Analyst 141:1997-2008
Jones, Paul V; Hayes, Mark A (2015) Development of the resolution theory for gradient insulator-based dielectrophoresis. Electrophoresis 36:1098-106
Kenyon, Stacy M; Keebaugh, Michael W; Hayes, Mark A (2014) Development of the resolution theory for electrophoretic exclusion. Electrophoresis 35:2551-9
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Woolley, Christine F; Hayes, Mark A (2013) Recent developments in emerging microimmunoassays. Bioanalysis 5:245-64
Kenyon, Stacy M; Weiss, Noah G; Hayes, Mark A (2012) Using electrophoretic exclusion to manipulate small molecules and particles on a microdevice. Electrophoresis 33:1227-35
Keebaugh, Michael W; Mahanti, Prasun; Hayes, Mark A (2012) Quantitative assessment of flow and electric fields for electrophoretic focusing at a converging channel entrance with interfacial electrode. Electrophoresis 33:1924-30
Yanashima, Ryan; GarcĂ­a, Antonio A; Aldridge, James et al. (2012) Cutting a drop of water pinned by wire loops using a superhydrophobic surface and knife. PLoS One 7:e45893