Abstract
A versatile microfluidic platform allowing co-culture of multiple cell populations in close proximity with separate control of their microenvironments would be extremely valuable for many biological applications. Here, we report a simple and compact microfluidic platform that has these desirable features and allows for real-time, live-cell imaging of cell-cell interactions. Using a pneumatically/hydraulically controlled poly(dimethylsiloxane) (PDMS) valve barrier, distinct cell types can be cultured in side-by-side microfluidic chambers with their optimum culture media and treated separately without affecting the other cell population. The platform is capable of both two-dimensional and three-dimensional cell co-culture and through variations of the valve barrier design, the platform allows for cell-cell interactions through either direct cell contact or soluble factors alone. The platform has been used to perform dynamic imaging of synapse formation in hippocampal neurons by separate transfection of two groups of neurons with fluorescent pre- and post-synaptic protein markers. In addition, cross-migration of 4T1 tumor cells and endothelial cells has been studied under normoxic and hypoxic conditions, which revealed different migration patterns, suggesting the importance of the microenvironments in cell-cell interactions and biological activities.
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Acknowledgements
We thank Anne Marie Craig, Mark Dewhirst, and Freda Miller for kindly providing us with reagents and Dmitry Markov for helpful discussions. We also thank Lan Hu for technical assistance in preparing neuronal cultures. This work was supported by grants MH071674 and GM092914 from NIH and S10RR025524 from the National Center for Research Resources at NIH to D.J.W. and grant CBET0643583 from NSF and W81XWH-07-1-0507 from DoD to D.L.
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Gao, Y., Majumdar, D., Jovanovic, B. et al. A versatile valve-enabled microfluidic cell co-culture platform and demonstration of its applications to neurobiology and cancer biology. Biomed Microdevices 13, 539–548 (2011). https://doi.org/10.1007/s10544-011-9523-9
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DOI: https://doi.org/10.1007/s10544-011-9523-9