Point-of-care assays for therapeutic drug monitoring

Overview: Therapeutic drug monitoring (TDM) may become an essential component of personalized medicine, but the tools to facilitate TDM are currently too cumbersome and expensive for routine clinical use especially in resource-limited settings. The need for TDM is urgent in human immunodeficiency virus (HIV) care, where maintaining therapeutic levels of antiretroviral therapy (ART) is critical, and yet nearly half of people do not maintain adequate adherence. Subtherapeutic drug concentrations put people at risk for developing drug-resistant virus, having persistent HIV viremia, immune dysregulation, and death. The long-term goal of my research is to develop point- of-care (POC) technologies for TDM and precision medicine in global health settings. I recently developed the REverSe TRanscrIptase Chain Termination (RESTRICT) enzymatic assay for rapid measurement of nucleotide reverse transcriptase inhibitors (NRTIs) – the backbone of HIV treatment and prevention regimens and thus an optimal target for HIV TDM. RESTRICT infers drug levels based on DNA chain termination. I demonstrated proof-of-concept RESTRICT assays with tenofovir diphosphate (TFV-DP), an NRTI used in over 90% of HIV treatment regimens and in all HIV prevention regimens. RESTRICT has immediate applications for measuring adherence to HIV medication and screening patients during HIV vaccine efficacy trials. My lab will develop assays for therapeutic monitoring of other enzyme inhibitors used in infectious and chronic disease management.

Key Publications:

  1. Olanrewaju A.O, Sullivan B, Gim A, Sevenler D, Bender A, Drain P, Posner J. (2021) REverSe TranscrIptase Chain Termination (RESTRICT) for Selective Measurement of Nucleotide Analogs Used in HIV Care and Prevention. ChemRxiv. [Preprint]. DOI: 10.33774/chemrxiv-2021-q65sr

  2. Olanrewaju A.O, Sullivan B.P, Bardon A.R, Lo T.J, Cressey T.R, Posner J.D, Drain P.K, (2021) Pilot Evaluation of a Rapid Enzymatic Assay for Measuring Antiretroviral Drug Concentrations. Virology Journal, 18(77), DOI: 10.1186/s12985-021-01543-x

  3. Olanrewaju A.O, Sullivan B.P, Zhang J.Y, Bender A.T, Sevenler D, Lo T.J, Fernandez-Suarez M, Drain P.K, and Posner J.D. (2020) Enzymatic Assay for Rapid Measurement of Antiretroviral Drug Levels. ACS Sensors, 5(4), 952 – 959. DOI:10.1021/acssensors.9b02198

Capillary microfluidics for rapid and user-friendly liquid delivery

Overview: Prior to this work, the conventional view was that self-powered and self-regulated microfluidic devices, that move liquids using only capillary forces defined by microchannel geometry and surface chemistry, required the high precision (~10 μm) and sub-micron surface roughness provided by cleanroom fabrication. Cleanroom fabrication increases the time and cost required to develop new designs and limits self-powered microfluidics to small volumes (≤10 μL) preventing their use in applications that where large sample volumes (>100 μL) need to be screened (e.g., bacteria detection in urine). I conceived the idea to 3D-print self-powered microfluidics, developed design rules to ensure that they remained functional even with the larger dimensions and rougher surfaces achievable by 3D printing, and conducted proof of concept experiments to demonstrate pre-programmed liquid delivery. I applied these 3D-printed capillary microfluidic devices to detect clinically relevant bacteria concentrations in < 7 min. These self-powered microchips could provide rapid, sensitive, and user-friendly diagnosis of urinary tract infections in vulnerable and non-verbal populations such as infants.

Key Publications:

  1. Olanrewaju A.O, Beaugrand M, Yafia M, and Juncker D. (2018) Capillary microfluidics in microchannels: from microfluidic networks to capillaric circuits, Lab on a Chip, 18 (16), 2323-2347. DOI:10.1039/C8LC00458G

  2. Olanrewaju A.O, Ng A, DeCorwin-Martin P, Robillard A*, and Juncker D. (2017) Microfluidic Capillaric Circuit for Rapid and Facile Bacteria Detection, Analytical Chemistry, 89, 6846 – 6853. DOI:10.1021/acs.analchem.7b01315

  3. Olanrewaju A.O, Robillard A*, Dagher M, and Juncker D. (2016) Autonomous Microfluidic Capillaric Circuits Replicated from 3D-Printed Molds”, Lab on a Chip, 16 (19), 3804 – 3814. DOI:10.1039/C6LC00764C.