Article

Biomedical Microdevices

, Volume 13, Issue 3, pp 539-548

A versatile valve-enabled microfluidic cell co-culture platform and demonstration of its applications to neurobiology and cancer biology

  • Yandong GaoAffiliated withDepartment of Mechanical Engineering, Vanderbilt University
  • , Devi MajumdarAffiliated withDepartment of Biological Sciences and Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University
  • , Bojana JovanovicAffiliated withDepartment of Cancer Biology, Vanderbilt University
  • , Candice ShaiferAffiliated withDepartment of Biochemistry and Cancer Biology, Meharry Medical College
  • , P. Charles LinAffiliated withCenter for Cancer Research, National Cancer Institute
  • , Andries ZijlstraAffiliated withDepartment of Pathology, Vanderbilt University
  • , Donna J. WebbAffiliated withDepartment of Biological Sciences and Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt UniversityDepartment of Cancer Biology, Vanderbilt University
  • , Deyu LiAffiliated withDepartment of Mechanical Engineering, Vanderbilt University Email author 

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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.

Keywords

Cell culture Cell-cell interaction Synapse formation Cell migration