Human immunodeficiency virus (HIV) has caused more than 39 million deaths and takes the lives of more than 1.5 million people per year. Antiretroviral therapy (ART) has been highly effective in reducing mortality and expanding access to ART in developing countries has averted more than 5 million HIV-related deaths. The expansion of access to ART has given rise to urgent challenges in early diagnosis, timely ART initiation, and treatment monitoring for timely diagnosis of ART failure in resource-limited settings, where there are limited laboratory infrastructure and trained staff. Regular viral load testing is the most accurate and preferred approach for ART monitoring and is recognized and recommended by the World Health Organization (WHO) guidelines for HIV management in resource-limited settings. In developed countries, nucleic acid-based assays are used for HIV load testing. However, these assays are expensive, laboratory-based, and technically complex, and cannot be easily accessed in resource-limited settings. Thus, to increase access to HIV care with regular ART monitoring in low- and middle-income countries, there is an urgent need for inexpensive, rapid, sensitive, and specific HIV load monitoring tools. In this proposal, building upon our prior expertise, we will use nano- and micro-scale approaches to develop a reliable microchip platform for point-of-care (POC) viral load testing. Our proposed platform technology relies on three engineering and biology related technological advances: (i) on-chip capture of multiple HIV subtypes using anti-gp120/gp41 antibodies with high efficiency and specificity, (ii) sensitive label-free electrical detection of viral lysate using a portable system and (iii) paper- based microfluidics with printed flexible graphene-modified electrodes. Our microchip fabrication is simple, inexpensive, and mass-producible as we print microelectrodes on paper substrates using conductive inks for only a few pennies per chip. Our prior published work has shown the proof-of-concept that multiple HIV subtypes (A, B, C, D, E, G, and panel) can be selectively captured and detected from a fingerprick volume of blood (<100 L) with clinically relevant virus concentrations for ART monitoring using electrical sensing of viral lysate on-chip. This diagnostic platform technology is broadly applicable to other infectious diseases such as hepatitis, malaria, pox, tuberculosis, and influenza. We have shown the ability of the proposed microchip technology to detect KSHV, EBV, and E. coli in biological samples. The main aim of the proposed study is developing an inexpensive (<$1), disposable, and mass-producible paper-based microfluidic device that is automated to handle whole blood samples (<100 L) and to rapidly (<30 minutes) detect and count HIV.

Public Health Relevance

Rapid, inexpensive, and early detection of infectious diseases is an urgent need with broad applications such as clinical diagnosis, public health, and homeland security. Of particular interest is regular HIV load measurement in patients on antiretroviral therapy (ART) to diagnose ART failure in low- and middle-income countries. This project seeks to develop a breakthrough microchip technology for rapid, inexpensive, and selective viral load testing at the point-of-care by integrating label-free electrical sensing and paper-based microfluidics.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI118502-03
Application #
9402576
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Fitzgibbon, Joseph E
Project Start
2016-01-01
Project End
2020-12-31
Budget Start
2018-01-01
Budget End
2018-12-31
Support Year
3
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
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Safavieh, Mohammadali; Pandya, Hardik J; Venkataraman, Maanasa et al. (2017) Rapid Real-Time Antimicrobial Susceptibility Testing with Electrical Sensing on Plastic Microchips with Printed Electrodes. ACS Appl Mater Interfaces 9:12832-12840
Coarsey, Chad T; Esiobu, Nwadiuto; Narayanan, Ramswamy et al. (2017) Strategies in Ebola virus disease (EVD) diagnostics at the point of care. Crit Rev Microbiol 43:779-798

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