Miniaturising organoid drug screens using nanofibrillar cellulose hydrogels

Drug testing on advanced cell-based models such as organoids has gained in popularity, but significant technical hurdles remain that prevent further assay miniaturisation and higher assay throughput. Through the replacement of animal-derived basement membranes with wood-derived nanofibrillar cellulose hydrogel (NFC), Dr Tijmen Booij and Dr Christian Stirnimann from ETH Zurich, Switzerland have developed an organoid drug-screening platform that is largely animal-free, cheap to run and pipette-tip free to reduce plastic waste in screening assays.

Advanced cell-based assays in drug discovery

The physiological relevance of drug evaluations in cell-based assays is often limited by the use of simplified biological models, such as two-dimensionally (2D) cultured immortalised cell lines. While such models have been essential to elucidate cellular signalling pathways as well as find and evaluate drug targets, correct prediction of in vivo drug responses based on simplistic in vitro tests remains challenging.

In recent decades there have been impressive technological achievements in the development of alternative in vitro assays that are better at mimicking pathophysiology. Key innovations in this field have been the development of three‑dimensional (3D) cell culture models, such as multicellular tumour spheroids, (patient-derived) organoids and organ‑on‑a‑chip technologies that are thought to better recapitulate human physiology and pathophysiology. Despite it being too early to be certain that the identification of drugs and drug targets using such assays results in higher success rates of drug candidates in the clinic, these advanced assays are gaining in popularity for large‑scale drug testing.

A predominant technological restraint in upscaling drug testing with advanced cell culture models is that typically the materials and reagents that are used have not been designed with high-throughput screening applications in mind. In this article, we will outline the strategy we applied to upscale organoid-based screens to a 1,536-well plate format and discuss some of the challenges along the way.