A novel platform for automated production and screening of
scaffold-free organotypic microtissues
A toploadable 96-well hanging drop culture system enables automated mass production of primary and tumor microtissues.
To meet the urgent need for automation-formatted, highly biomimetic microtissues, suitable for use at all stages of in vitro pr-clinical discovery and predictive toxicology.
Although the advantages of organotypic 3D-cell-culture models have been known for years, complex production and readout processes impeded its industrial implementation. In this study, we present a novel high throughput-compatible 96-well platform to produce organotypic, scaffold-free microtissues and its implementation in an automated screening process. This technology allows you to produce tumor and primary microtissues in a hanging-drop culture by liquid top-loading similar to standard 96-well monolayer plates. We present the implementation of this system on a Hamilton NIMBUS robotic liquid-handling device with a 96-multichannel pipette head. Volumetric precision was comparable in standard multi-well plates, resulting in low batch to batch variations of microtissues. Further we demonstrate the screening-compatibility with 4 reference compounds for early stage applications and the possibility to perform more detailed analysis by e.g. Immunohistology. Overall, we could demonstrate that organotypic microtissues can be applied in an automated screening campaign using standard liquid-handling robotics to improve the in-vitro elevation of drug candidates.