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      Side view thrombosis microfluidic device with controllable wall shear rate and transthrombus pressure gradient.

      1 ,
      Lab on a chip
      Royal Society of Chemistry (RSC)

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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) cm(2), while the platelet/fibrin thrombus on collagen/TF had a permeability of 2.71 × 10(-14) cm(2) (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.

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          Author and article information

          Journal
          Lab Chip
          Lab on a chip
          Royal Society of Chemistry (RSC)
          1473-0189
          1473-0189
          May 21 2013
          : 13
          : 10
          Affiliations
          [1 ] Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
          Article
          NIHMS464445
          10.1039/c3lc41332b
          3660965
          23549358
          26ed9e5d-64e1-4194-8679-51f933e5e19c
          History

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