An Active Micropump-mixer for Rapid Anti-platelet Drug Screening in Whole Blood.

Abstract

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 anti-platelet therapies. This paper reports on the development and characteriza-tion 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 3-dimensional hemodynamics of micropump operation in conjunction with a microvalve controlled reagent injection system we demonstrate that this prototype can act as a real-time assay of anti-platelet drug pharmacokinetics. In a proof-of-concept pre-clinical application we utilize this system to investigate the way in which rapid dosing of human whole blood with isoform se-lective inhibitors of phosphatidylinositol 3-kinase dose dependently modulate platelet thrombus dynamics. This modular sys-tem exhibits utility as an automated multiplexable assay system with applications to high-content chemical library screening of new antiplatelet therapies.