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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Platelets / drug effects
  • Hemodynamics
  • Humans
  • Indomethacin / blood*
  • Indomethacin / pharmacokinetics
  • Lab-On-A-Chip Devices*
  • Microfluidic Analytical Techniques* / instrumentation
  • Platelet Aggregation Inhibitors / blood*
  • Platelet Aggregation Inhibitors / pharmacokinetics

Substances

  • Platelet Aggregation Inhibitors
  • Indomethacin