We describe a microfluidic system that can control, in real time, the microenvironments of mammalian cells in naturally derived 3D extracellular matrix (ECM). This chip combines pneumatically actuated valves with an individually addressable array of 3D cell-laden ECM; actuation of valves determines the pathways for delivering reagents through the chip and for exchanging diffusible factors between cell chambers. To promote rapid perfusion of reagents through 3D gels (with complete exchange of reagents within the gel in seconds), we created conduits above the gels for fluid flow, and microposts to stabilize the gels under high perfusion rates. As a biological demonstration, we studied spatially segregated mouse embryonic stem cells and mouse embryonic fibroblasts embedded in 3D Matrigel over days of culture. Overall, this system may be useful for high-throughput screening, single-cell analysis and studies of cell-cell communication, where rapid control of 3D cellular microenvironments is desired.

Microfluidics is a technology that features the movement of small volumes of fluids through microscale channels. It provides a powerful and precise research platform for studying basic phenomena of fluid flow at the microscale, and a powerful analytical platform for conducting experimental assays. This article discusses the basic features and applications of microfluidics.