Active Micropump-Mixer for Rapid Antiplatelet Drug Screening in Whole Blood
2019
Szydzik, Crispin | Brazilek, Rose J. | Akbaridoust, Farzan | de Silva, Charitha | Moon, Mitchell | Marusic, Ivan | Ooi, Andrew S. H. | Nandurkar, Harshal H. | Hamilton, Justin R. | Mitchell, Arnan | Nesbitt, Warwick S.
There is a need for scalable automated lab-on-chip systems incorporating precise hemodynamic control that can be applied to high-content screening of new more efficacious antiplatelet therapies. This paper reports on the development and characterization of a novel active micropump-mixer microfluidic to address this need. Using a novel reciprocating elastomeric micropump design, we take advantage of the flexible structural and actuation properties of this framework to manage the hemodynamics for on-chip platelet thrombosis assay on type 1 fibrillar collagen, using whole blood. By characterizing and harnessing the complex three-dimensional hemodynamics of the micropump operation in conjunction with a microvalve controlled reagent injection system we demonstrate that this prototype can act as a real-time assay of antiplatelet drug pharmacokinetics. In a proof-of-concept preclinical application, we utilize this system to investigate the way in which rapid dosing of human whole blood with isoform selective inhibitors of phosphatidylinositol 3-kinase dose dependently modulate platelet thrombus dynamics. This modular system exhibits utility as an automated multiplexable assay system with applications to high-content chemical library screening of new antiplatelet therapies.
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