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Issue 4, 2007

Vascular mimetics based on microfluidics for imaging the leukocyte–endothelial inflammatory response

Author affiliations

Abstract

We describe the development, validation, and application of a novel PDMS-based microfluidic device for imaging leukocyte interaction with a biological substrate at defined shear force employing a parallel plate geometry that optimizes experimental throughput while decreasing reagent consumption. The device is vacuum bonded above a standard 6-well tissue culture plate that accommodates a monolayer of endothelial cells, thereby providing a channel to directly observe the kinetics of leukocyte adhesion under defined shear flow. Computational fluid dynamics (CFD) was applied to model the shear stress and the trajectory of leukocytes within the flow channels at a micron length scale. In order to test this model, neutrophil capture, rolling, and deceleration to arrest as a function of time and position was imaged in the transparent channels. Neutrophil recruitment to the substrate proved to be highly sensitive to disturbances in flow streamlines, which enhanced the rate of neutrophil–surface collisions at the entrance to the channels. Downstream from these disturbances, the relationship between receptor mediated deceleration of rolling neutrophils and dose response of stimulation by the chemokine IL-8 was found to provide a functional readout of integrin activation. This microfluidic technique allows detailed kinetic studies of cell adhesion and reveals neutrophil activation within seconds to chemotactic molecules at concentrations in the picoMolar range.

Graphical abstract: Vascular mimetics based on microfluidics for imaging the leukocyte–endothelial inflammatory response

Article information


Submitted
08 Aug 2006
Accepted
02 Jan 2007
First published
23 Jan 2007

Lab Chip, 2007,7, 448-456
Article type
Paper

Vascular mimetics based on microfluidics for imaging the leukocyte–endothelial inflammatory response

U. Y. Schaff, M. M. Q. Xing, K. K. Lin, N. Pan, N. L. Jeon and S. I. Simon, Lab Chip, 2007, 7, 448 DOI: 10.1039/B617915K

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