Development of a Microfluidic Platform
Development of a Microfluidic Organoid Culture Platform
Cell-based assays are essential for drug discovery and diagnostic developments, since they enable screening of candidate drug molecules, detection of molecular markers associated with diseases, and fundamental studies in cell and molecular biology. Conventional cell-based assays are typically static and, thus, not representative of the spatially complex and highly dynamic context observed in living tissues. Over the last decade, organ-on-a-chip approaches based on microfluidics have been developed to address this issue, because they enable dynamic changes of the cell culture medium composition through flow of different solutions around immobilized cells. Despite exciting prospects and some encouraging results, state-of-the-art organ-on-a-chip technology has significant shortcomings, such as the dependency on non-physiological materials (e.g. poly(dimethylsiloxane)) that suffer from liquid evaporation and protein adsorption, and are unconducive to grow primary (stem and tumor) cells into functional miniature tissues, termed ‘organoids’. Furthermore, the continuous exposure of cells to fluid flow in such devices results in the depletion of crucial autocrine signals and establishment of shear stresses, both negatively impacting cell behavior, tissue development and long-term function.
The overarching goal of Module 4 was to establish a versatile microfluidic organoid culture platform for the unprecedented in vitro study of tissue and disease biology. This platform was used to study intestinal organoids as model system to understand the fascinating emergent properties by which cell build patterned tissues themselves, as this will allow us in the future to engineer tissues with much more precision and improved function. The platform is further being used to study breast cancer organoids (‘tumoroids’) as model system with the goal to understand the role of inflammation in cancer initiation and progression.