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Issue 10, 2013
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Side view thrombosis microfluidic device with controllable wall shear rate and transthrombus pressure gradient

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Abstract

Hemodynamic conditions vary throughout the vasculature, creating diverse environments in which platelets must respond. To stop bleeding, a growing platelet deposit must be assembled in the presence of fluid wall shear stress (τw) and a transthrombus pressure gradient (ΔP) that drives bleeding. We designed a microfluidic device capable of pulsing a fluorescent solute through a developing thrombus forming on collagen ± tissue factor (TF), while independently controlling ΔP and τw. Computer control allowed step changes in ΔP with a rapid response time of 0.26 mm Hg s−1 at either venous (5.2 dynes cm−2) or arterial (33.9 dynes cm−2) wall shear stresses. Side view visualization of thrombosis with transthrombus permeation allowed for quantification of clot structure, height, and composition at various ΔP. Clot height was reduced 20% on collagen/TF and 28% on collagen alone when ΔP was increased from 20.8 to 23.4 mm Hg at constant arterial shear stress. When visualized with a platelet-targeting thrombin sensor, intrathrombus thrombin levels decreased by 62% as ΔP was increased from 0 to 23.4 mm Hg across the thrombus-collagen/TF barrier, consistent with convective removal of thrombogenic solutes due to pressure-driven permeation. Independent of ΔP, the platelet deposit on collagen had a permeability of 5.45 × 10−14 cm2, while the platelet/fibrin thrombus on collagen/TF had a permeability of 2.71 × 10−14 cm2 (comparable to that of an intact endothelium). This microfluidic design allows investigation of the coupled processes of platelet deposition and thrombin/fibrin generation in the presence of controlled transthrombus permeation and wall shear stress.

Graphical abstract: Side view thrombosis microfluidic device with controllable wall shear rate and transthrombus pressure gradient

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Publication details

The article was received on 04 Dec 2012, accepted on 08 Mar 2013 and first published on 08 Mar 2013


Article type: Paper
DOI: 10.1039/C3LC41332B
Citation: Lab Chip, 2013,13, 1883-1891
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    Side view thrombosis microfluidic device with controllable wall shear rate and transthrombus pressure gradient

    R. W. Muthard and S. L. Diamond, Lab Chip, 2013, 13, 1883
    DOI: 10.1039/C3LC41332B

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