Applications of microfluidic devices in advancing NK-cell migration studies.

Abstract

Understanding how NK cells interact with tumor cells under specific microenvironment will be informative in development of NK-cell based immunotherapy. Applications of microfluidic devices in in vitro studies of NK-cell migrations offer unique opportunities to examine NK-cell migrations at single-cell under controlled cellular microenvironments. Novel devices can be created and engineered to present precise configuration that mimics cellular microenvironments for cell migration studies. We established previously the first application of a simple Y-shaped device for imaging and analysis of the abilities of the immature and mature DC to regulate murine IL-2 activated NK cell migrations. Here we reported the application of our recent technical development of a novel microfluidic device, which is also called the triple docking device (i.e., D3-Chip), for the studies of NK-cell migrations in NK-4T1 breast cancer cell interactions in vitro. Key features of this microfluidic device are its pump-free gradient generation, and the three-parallel units design that supports easy setup and parallel comparison of multiple experimental conditions. The cell docking structure enables the prealignment of all NK cells at the same "start" position before their exposures to the test conditions. As a result, quantification of cell displacement toward a chemical gradient can be quantified by enumeration of the number of cells migrated out of the docking structure and their displacements. Such microfluidic devices can be further modified in future to mimic the complex in vivo microenvironments to support more advanced investigations of NK-cell migratory responses in vitro.