The HIV/AIDS pandemic is one of the single greatest global health challenges of contemporary society that disproportionally affects young women, especially in many of the world's poorest regions. With 25 million dead and another 35 million infected, prevention, diagnosis, and treatment are all crucial components of any plan to curb the disease. While no cure exists, antiretroviral therapies (ART) have proven successful in slowing down the progression of the disease by maintaining low numbers of virus inside patients so that their CD4 counts are maintained at levels which can successfully fight off opportunistic infections. The World Health Organization (WHO) has identified Viral Load (VL) testing as the preferred method to monitor patients on ART; however, current gold-standard techniques rely on nucleic-acid testing which are dependent on expensive, technically challenging equipment with a requirement for infrastructure such as stable electricity and temperature control. The inability to perform VL testing in many of the areas most heavily affected by the disease has left hospitals and clinics to rely on less-accurate diagnostics. This proposal seeks to develop a point of care testing solution that will address the needs of clinicians and patients across the world who do not have access to VL testing. The proposed solution will sense the number of virus particles in a 100 L sample of patient blood using a microfluidic chip attached to a photonic crystal which is read by a custom optical cradle attached to a standard smartphone and sensitive down to at least 200 copies/mL, 5x below the WHO established threshold for ART monitoring. To accomplish this, a self-referencing optical cradle will be designed based upon working proof-of-concept prototypes that will then be characterized for both spectral resolution and sensitivity to biological attachment using the interactions between HIV-1 gp120 and anti-gp120. A microfluidic chip will be designed on top of a photonic crystal (PC) biosensor to decrease the working volumes, increase sensitivity, and increase ease-of-use. This system will then be tested on spiked patient plasma samples to quantify a limit of detection (LOD) for the device. Further improvements of the LOD will be achieved by further miniaturizing the microfluidics device through a manufacturing process based upon electrohydrodynamic-jet printing, and refractive-index based signal amplifying molecules. Finally, whole blood samples will be used to determine a new LOD and samples from HIV positive and negative patients will be used to validate the utility of the system.
Over 35 million people globally are infected with HIV/AIDS, a disease affects the poorest regions of the world; it disproportionally targets young women and it cannot be cured. It can, however, be treated by antiretroviral therapies, if the therapies are properly monitored. The World Health Organization has identified viral load testing as the preferred method for monitoring; however, current testing methods are too technically complicated, infrastructure dependent, and financially burdensome for the majority of countries most affected by the disease. This application seeks to develop and test a point-of-care diagnostic platform capable of measuring HIV viral load with a finger prick, a disposable cartridge costing under $10, and an attachment that snaps onto a portable smartphone device, thereby providing diagnostic information in less than 2 hours and with minimal cost.
| Long, Kenneth D; Woodburn, Elizabeth V; Le, Huy M et al. (2017) Multimode smartphone biosensing: the transmission, reflection, and intensity spectral (TRI)-analyzer. Lab Chip 17:3246-3257 |
