To reduce morbidity and improve quality of life for persons living with HIV/AIDS, the World Health Organization (WHO) is rapidly expanding access to antiretroviral therapy (ART) in developing countries. However, the expansion is significantly restricted by the lack of cost-effective point-of-care (POC) viral load assays that cn effectively reach patients living in rural, isolated settings. In developed countries, HIV-1 viral load is regularly used to closely monitor and assess the patient response to ART, to ensure drug adherence and to stage disease progression. In contrast, developing countries are using CD4+ cell count and clinical symptoms to guide ART following the WHO guidelines with the exception of infants, where viral load assays are required. This is because HIV-1 viral load assays are expensive ($50-200 per test), instrument-dependent, and technically complex. Recent studies, however, have shown that CD4 cell counting strategy cannot detect early virological failure. This failure leads to accumulation of drug-resistant strains in infected individuals and reduces the efficacy of first-line drugs. Thus, a rapid, inexpensive, and simple viral load test is urgently needed at the point of care (POC). Here, microfluidics and optical imaging technologies will be used to create a novel HIV-1 viral load microchip. It was hypothesized that the developed HIV-1 viral load microchip can: (i) selectively capture HIV from whole blood, (ii) be sensitive within the clinical cut-off (with ?10% error range), inexpensive (<$1), rapid (within 15 minutes), and automated to handle finger-prick whole blood (100 ?L) to aid in quality care and treatment at the POC. This is a technology driven proposal motivated by the urgent significant clinical need. Prior work has shown the proof-of-concept that HIV-1 can be captured and quantified from patient whole blood on-chip. The following distinct but interrelated specific aims are proposed:
Aim 1 : To build disposable microchips to capture HIV-1, Aim 2: To develop a portable system for on-chip HIV-1 viral load by integrating HIV-1 capturing microchips with a detection/quantification system, and Aim 3: To validate the microchip technology with 200 HIV-infected samples. This proposed technology is broadly applicable to other infectious diseases having a reasonably well-described biomarker available such as influenza, hepatitis, malaria and tuberculosis.

Public Health Relevance

To reduce morbidity and to improve quality of life for people living with HIV/AIDS, the access to antiretroviral treatment is rapidly expanding in developing countries. However, this expansion is significantly restricted by the lack of cost-effective viral load monitoring tools. To aid in quality care and treatment of people living with HIV/AIDS, we propose a novel HIV viral load microchip, which is: (i) capable of selectively capturing HIV from whole blood, (ii) sensitive within the clinical cut-off (with ?10%) error range, inexpensive (<$1), rapid (within 15 minutes), and automated to handle finger-prick whole blood (100 ?L).

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI093282-01A1
Application #
8411025
Study Section
Special Emphasis Panel (ZRG1-AARR-E (11))
Program Officer
Fitzgibbon, Joseph E
Project Start
2012-07-15
Project End
2016-06-30
Budget Start
2012-07-15
Budget End
2013-06-30
Support Year
1
Fiscal Year
2012
Total Cost
$446,250
Indirect Cost
$196,250
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Sher, Mazhar; Zhuang, Rachel; Demirci, Utkan et al. (2017) Paper-based analytical devices for clinical diagnosis: recent advances in the fabrication techniques and sensing mechanisms. Expert Rev Mol Diagn 17:351-366
Liang, Li-Guo; Kong, Meng-Qi; Zhou, Sherry et al. (2017) An integrated double-filtration microfluidic device for isolation, enrichment and quantification of urinary extracellular vesicles for detection of bladder cancer. Sci Rep 7:46224
Inan, Hakan; Poyraz, Muhammet; Inci, Fatih et al. (2017) Photonic crystals: emerging biosensors and their promise for point-of-care applications. Chem Soc Rev 46:366-388
Lifson, Mark A; Ozen, Mehmet Ozgun; Inci, Fatih et al. (2016) Advances in biosensing strategies for HIV-1 detection, diagnosis, and therapeutic monitoring. Adv Drug Deliv Rev 103:90-104
Baday, Murat; Calamak, Semih; Durmus, Naside Gozde et al. (2016) Integrating Cell Phone Imaging with Magnetic Levitation (i-LEV) for Label-Free Blood Analysis at the Point-of-Living. Small 12:1222-1229
Asghar, Waseem; Yuksekkaya, Mehmet; Shafiee, Hadi et al. (2016) Engineering long shelf life multi-layer biologically active surfaces on microfluidic devices for point of care applications. Sci Rep 6:21163
Wang, ShuQi; Chinnasamy, Thiruppathiraja; Lifson, Mark A et al. (2016) Flexible Substrate-Based Devices for Point-of-Care Diagnostics. Trends Biotechnol 34:909-921
El Assal, Rami; Gurkan, Umut A; Chen, Pu et al. (2016) 3-D Microwell Array System for Culturing Virus Infected Tumor Cells. Sci Rep 6:39144
Shafiee, Hadi; Kanakasabapathy, Manoj Kumar; Juillard, Franceline et al. (2015) Printed Flexible Plastic Microchip for Viral Load Measurement through Quantitative Detection of Viruses in Plasma and Saliva. Sci Rep 5:9919
Tokel, Onur; Yildiz, Umit Hakan; Inci, Fatih et al. (2015) Portable microfluidic integrated plasmonic platform for pathogen detection. Sci Rep 5:9152

Showing the most recent 10 out of 26 publications