Abstract

Microfluidic Platform for 3D Spherical Microtissues: Culturing and Imaging Approaches for Multi-Cell-Based Assays

Olivier Frey, Head of Technology and Platforms, InSphero AG

In-vitro cell-based assays play a key role in the overall process of drug discovery and can provide essential information on the efficacy and toxicity of a new compound. In order to increase the predictability of such assays, 3-dimenstional tissue constructs receive more and more attention, as their organotypic nature is better suited to study complex physiological processes than that of 2-dimensional cell cultures, which is not only dependent on the fabrication method of 3-dimensional tissue structures, as the utilized microenvironment also strongly influences long-term viability and functionality. In our lab, we focus on spherical microtissues, produced by the hanging drop technology, as they offer two key advantages over other cell culture formats that have been used in conjunction with microfluidic networks for cell-based assays: First, they are comparably simple and reproducible to fabricate, and possess organotypic functionality and biomimetic morphology. Second, their spherical shape and compact constitution, as well as their precisely controllable size make them ideal candidates for handling in microfluidic structures in contrast to 3D-hydrogel or scaffold-based cell-cultures. Combining the advantages of spheroids and the technical capabilities of microfluidic engineering offers the possibility to develop a modular platform that accommodates multiple tissues of different cell types (e.g. tumor, liver, heart). Dedicated culturing compartments host the microtissues, and fluidic interconnections between these compartments allow for mimicking the physiological context and conditions of the human body. Further, microfabrication technologies allow the direct integration of microelectrodes for tissue monitoring via electrical impedance spectroscopy, a label-free and complementary read-out to optical microscopy.