Part 11. Automation- and miniaturization of organoid assays for drug screening

Basics to 3D cell culture automation - what to consider when scaling up your assays

Over the last years, drug screens with organoids have gained in popularity due to their improved physiological relevance, which is expected to reduce the number and size of in vivo studies that are required to confirm in vitro results. Currently most organoid screens are being performed in the range of hundreds to perhaps a few thousand compounds per screen. From the technical perspective, setting up high-throughput screens with organoids is still a challenge. On the one hand this is due to the availability of sufficient organoids, but on the other hand also because of the reagents that are traditionally used.

As technology platform of the ETH Zürich, NEXUS has over the last couple of years performed several successful organoid screens for different disease systems, where we observed that animal-derived hydrogels are a consistent source of variation and additionally complicate the automation of screening assays. To improve throughput and remove potential sources of variation in our organoid screens, we optimized screening conditions using organoid models for Hepatocellular Carcinoma with UPM Biomedicals’ GrowDex and GrowDex-T. We report the successful adaptation of our organoid screening methodology for these HCC organoid lines, and expect that a similar conversion will be possible for many other organoid types.