Real-time microfluidic system for studying mammalian cells in 3D microenvironments.
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.
Lii
Jerry
J
Department of Biomedical Engineering, Columbia University, 351 Engineering Terrace, 1210 Amsterdam Avenue, New York, New York 10027, USA.
Hsu
Wern-Jir
WJ
Parsa
Hesam
H
Das
Anshu
A
Rouse
Robert
R
Sia
Samuel K
SK
D000818:Animals; D002478:Cells, Cultured; D003094:Collagen; D004338:Drug Combinations; D005109:Extracellular Matrix; D007797:Laminin; D051379:Mice; D044085:Microfluidics / Q000295:instrumentation*; D008856:Microscopy, Fluorescence; D011509:Proteoglycans
D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen