A capillary-endothelium-mimetic microfluidic chip for the study of immune responses

The transwell system is the most widely used tool for studying chemotaxis and understanding chemotactic responses. It has been suggested that chemotactic gradients attract neutrophils, leading to extravasation, but recent findings also implicate vascular hydrodynamic forces in chemotactic responses. With this motivation, we developed a Labchip that mimics the dynamic three-dimensional microenvironment of a blood vessel. This capillary-endothelium-mimetic (CEM) microfluidic chip serves as a dynamic transwell system for studying neutrophil migration at different flow velocities. Under lower flow rates, the chemotactic factor dominates over the flow rate, increasing the extravasation of neutrophil-like cells; at higher flow rates, the neutrophil-like cells aggregate near the side wall of the chamber due to a hydrodynamic force, limiting extravasation. In this report, we demonstrate the use of this Labchip for studying extravasation behavior over an extended period of time, under conditions of continuous flow and a stable concentration gradient. This Labchip-based approach is also applicable to the study of cancer metastasis, atherosclerosis and other angiopathies. (C) 2014 Elsevier B.V. All rights reserved.