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.
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).
|Shafiee, Hadi; Lidstone, Erich A; Jahangir, Muntasir et al. (2014) Nanostructured optical photonic crystal biosensor for HIV viral load measurement. Sci Rep 4:4116|
|Tokel, Onur; Inci, Fatih; Demirci, Utkan (2014) Advances in plasmonic technologies for point of care applications. Chem Rev 114:5728-52|
|Akkaynak, Derya; Treibitz, Tali; Xiao, Bei et al. (2014) Use of commercial off-the-shelf digital cameras for scientific data acquisition and scene-specific color calibration. J Opt Soc Am A Opt Image Sci Vis 31:312-21|
|Wang, ShuQi; Tasoglu, Savas; Chen, Paul Z et al. (2014) Micro-a-fluidics ELISA for rapid CD4 cell count at the point-of-care. Sci Rep 4:3796|
|Mani, Vigneshwaran; Wang, ShuQi; Inci, Fatih et al. (2014) Emerging technologies for monitoring drug-resistant tuberculosis at the point-of-care. Adv Drug Deliv Rev 78:105-17|
|Inci, Fatih; Tokel, Onur; Wang, Shuqi et al. (2013) Nanoplasmonic quantitative detection of intact viruses from unprocessed whole blood. ACS Nano 7:4733-45|
|Wang, ShuQi; Inci, Fatih; De Libero, Gennaro et al. (2013) Point-of-care assays for tuberculosis: role of nanotechnology/microfluidics. Biotechnol Adv 31:438-49|
|Shafiee, Hadi; Jahangir, Muntasir; Inci, Fatih et al. (2013) Acute on-chip HIV detection through label-free electrical sensing of viral nano-lysate. Small 9:2553-63, 2478|
|Tasoglu, Savas; Gurkan, Umut Atakan; Wang, Shuqi et al. (2013) Manipulating biological agents and cells in micro-scale volumes for applications in medicine. Chem Soc Rev 42:5788-808|