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

Muthard RW, Diamond SL. Side view thrombosis microfluidic device with controllable wall shear rate and transthrombus pressure gradient. Lab Chip May 21 2013; 13 (10): 1883-1891.

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

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

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.

A microfluidic device with controllable trans-scaffold pressure gradients. A microfluidic device with controllable trans-scaffold pressure gradients. Syringe pump inlet Q1 provided a constant volume flow that exited through the downstream outlet or transversed the collagen region towards the outlet monitored by P3 (A). The main flow channel (H = 60 mm, W = 250 mm) provided a collagen–fluid flow interface between pressure sensors P2 and P1 (B). A LabVIEW control panel interpreted the pressure measurements (P1, P2 and P3) and proportionately controlled a constant volume syringe pump (Q2) to maintain constant pressure gradients across the collagen region. Prior to use, the PDMS microfluidic device was vacuum sealed to a glass slide and connections between the tubing and device were made via 90u, 23-gauge blunt needle tips (C).

A microfluidic device with controllable trans-scaffold pressure gradients. 

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.

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