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

Ulrich Y. Schaff, Malcolm M Q Xing, Kathleen K. Lin, Ning Pan, Noo Li Jeon, Scott I. Simon

Research output: Contribution to journalArticle

102 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)448-456
Number of pages9
JournalLab on a Chip - Miniaturisation for Chemistry and Biology
Volume7
Issue number4
DOIs
StatePublished - 2007

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Microfluidics
Deceleration
Blood Vessels
Neutrophils
Leukocytes
Chemical activation
Lab-On-A-Chip Devices
Imaging techniques
Tissue culture
Kinetics
Cell adhesion
Endothelial cells
Substrates
Channel flow
Shear flow
Interleukin-8
Chemokines
Integrins
Shear stress
Monolayers

ASJC Scopus subject areas

  • Clinical Biochemistry

Cite this

Vascular mimetics based on microfluidics for imaging the leukocyte-endothelial inflammatory response. / Schaff, Ulrich Y.; Xing, Malcolm M Q; Lin, Kathleen K.; Pan, Ning; Jeon, Noo Li; Simon, Scott I.

In: Lab on a Chip - Miniaturisation for Chemistry and Biology, Vol. 7, No. 4, 2007, p. 448-456.

Research output: Contribution to journalArticle

Schaff, Ulrich Y. ; Xing, Malcolm M Q ; Lin, Kathleen K. ; Pan, Ning ; Jeon, Noo Li ; Simon, Scott I. / Vascular mimetics based on microfluidics for imaging the leukocyte-endothelial inflammatory response. In: Lab on a Chip - Miniaturisation for Chemistry and Biology. 2007 ; Vol. 7, No. 4. pp. 448-456.
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