A high-throughput compatible workflow for generation and analysis of homogenous human neural microtissues

Three dimensional (3D) cell culture in the form of organ-like micro tissues (“organoids”) has received increasing attention over the last 20 years. The potential of organoids to mimic cellular niches more closely than 2D cell cultures promises the advent of a new generation of high throughput screening (HTS) technologies providing superior predictions of drug efficacy and toxicity. 3D organoid-based disease models have already advanced understanding of diseases like microcephaly and ZIKA-virus pathogenesis, elucidating the dynamics of cells as they interact with tissue-specific cell types in complex cellular niches. Testing organoids instead of 2D cell cultures also has the potential to advance the understanding and therapy of human diseases such as Parkinson’s, Alzheimer’s and other disorders with complex interactions of several cell types in specific cellular niches.

While protocols for the generation of various types of organoids exist, these organoids remain widely incompatible with the standards for HTS. Most established strategies yield very heterogeneous organoids without predictable morphology, cellular composition, or local cellular organization. Extensive manual handling as well as matrix embedding is required prior to and during analysis, impeding industrial scale up.