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Issue 5, 2008
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A membrane-based microfluidic device for controlling the flux of platelet agonists into flowing blood

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Abstract

The flux of platelet agonists into flowing blood is a critical event in thrombosis and hemostasis. However, few in vitro methods exist for examining and controlling the role of platelet agonists on clot formation and stability under hemodynamic conditions. In this paper, we describe a membrane-based method for introducing a solute into flowing blood at a defined flux. The device consisted of a track-etched polycarbonate membrane reversibly sealed between two microfluidic channels; one channel contained blood flowing at a physiologically relevant shear rate, and the other channel contained the agonist(s). An analytical model described the solute flux as a function of the membrane permeability and transmembrane pressure. The model was validated using luciferase as a model solute for transmembrane pressures of 50–400 Pa. As a proof-of-concept, the weak platelet agonist ADP was introduced into whole blood flowing at 250 s−1 at three fluxes (1.5, 2.4, and 4.4 × 10−18 mol μm−2 s−1). Platelet aggregation was monitored by fluorescence microscopy during the experiment and the morphology of aggregates was determined by post hoc confocal and electron microscopy. At the lowest flux (1.5 × 10−18 mol μm−2 s−1), we observed little to no aggregation. At the higher fluxes, we observed monolayer (2.4 × 10−18 mol μm−2 s−1) and multilayer (4.4 × 10−18 mol μm−2 s−1) aggregates of platelets and found that the platelet density within an aggregate increased with increasing ADP flux. We expect this device to be a useful tool in unraveling the role of platelet agonists on clot formation and stability.

Graphical abstract: A membrane-based microfluidic device for controlling the flux of platelet agonists into flowing blood

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Publication details

The article was received on 20 Nov 2007, accepted on 12 Mar 2008 and first published on 03 Apr 2008


Article type: Paper
DOI: 10.1039/B717824G
Citation: Lab Chip, 2008,8, 701-709
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    A membrane-based microfluidic device for controlling the flux of platelet agonists into flowing blood

    K. B. Neeves and S. L. Diamond, Lab Chip, 2008, 8, 701
    DOI: 10.1039/B717824G

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