Parallelizable Microfluidic Platform to Model and Assess In Vitro Cellular Barriers: Technology and Application to Study the Interaction of 3D Tumor Spheroids with Cellular Barriers

Parallelizable Microfluidic Platform to Model and Assess In Vitro Cellular Barriers: Technology and Application to Study the Interaction of 3D Tumor Spheroids with Cellular Barriers
Nair A L , Mesch L, Schulz I, Becker H , Raible J, Kiessling H, Werner S, Rothbauer U , Schmees C, Busche M, Trennheuser S, Fricker G and Stelzle M
Biosensors 2021, 11, 314. https://doi.org/10.3390/bios11090314

Endothelial and epithelial cellular barriers play a vital role in the selective transport of
solutes and other molecules. The properties and function of these barriers are often affected in
case of inflammation and disease. Modelling cellular barriers in vitro can greatly facilitate studies
of inflammation, disease mechanisms and progression, and in addition, can be exploited for drug
screening and discovery. Here, we report on a parallelizable microfluidic platform in a multiwell
plate format with ten independent cell culture chambers to support the modelling of cellular barriers
co-cultured with 3D tumor spheroids. The microfluidic platform was fabricated by microinjection
molding. Electrodes integrated into the chip in combination with a FT-impedance measurement
system enabled transepithelial/transendothelial electrical resistance (TEER) measurements to rapidly
assess real-time barrier tightness. The fluidic layout supports the tubeless and parallelized operation
of up to ten distinct cultures under continuous unidirectional flow/perfusion. The capabilities of the
system were demonstrated with a co-culture of 3D tumor spheroids and cellular barriers showing
the growth and interaction of HT29 spheroids with a cellular barrier of MDCK cells.