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Anal Chem. 2019 Aug 20;91(16):10830-10839. doi: 10.1021/acs.analchem.9b02486. Epub 2019 Aug 6.

Active Micropump-Mixer for Rapid Antiplatelet Drug Screening in Whole Blood.

Author information

1
The Australian Centre for Blood Diseases , Monash University , 99 Commercial Road , Melbourne , Victoria 3004 , Australia.
2
School of Engineering , RMIT University , 124 La Trobe Street , Melbourne , Victoria 3000 , Australia.
3
Department of Mechanical Engineering, Melbourne School of Engineering , The University of Melbourne , Melbourne , Victoria 3010 , Australia.
4
School of Mechanical and Manufacturing Engineering , The University of New South Wales , Sydney , New South Wales 2052 , Australia.

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 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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