Enabling 3D hepatocyte spheroids for microphysiometry.

Advances in the areas of tissue engineering and microfabrication techniques have enabled promising in vitro platforms, known as Organs-on-Chips, with the aim of mimicking complex in vivo conditions for more accurate toxicology studies. To analyze the physiological change induced by chemicals or toxic substances continuously, sensors can be used in order to measure the intracellular and extracellular environment of single cells, cell constructs, or tissue, and therefore the integration of monitoring techniques into 3D tissue culture platforms provides an essential step for the next generation Organ-on-Chip platforms. However, current in vitro platforms are not capable of combining the culture of 3D models with monitoring techniques. To address this, a novel spheroid encapsulation is designed for fluidic contact between 3D models in microwells and Intelligent Mobile Lab for In Vitro Diagnostics (IMOLA-IVD) BioChip sensors while preventing spheroid fusion. In this work, spheroid culturing protocols were developed for optimized spheroid growth and an evaluation of spheroid integrity on different porous layers was performed in order to provide a defined spheroid encapsulation on BioChip sensors.