A novel platform for automated production and screening of scaffold-free, organotypic microtissues

Physiological tissue-like culture systems have shown to improve the relevance of in vitro testing of substances. Although the advantages of organotypic 3D-cell-culture models to increase the performance of in vitro compound assessment have been known for years, complex production and readout processes impeded its industrial implementation. Here, we present a novel automation-compatible 96-well platform to produce organotypic microtissues and its implementation in an automated screening process. this technology allows the production of tumor and primary microtissues in a scaffold-free hanging-drop culture by liquid top-loading similar to standard 96-well monolayer plates. This is achieved by a microfluidic channel connecting an inlet funnel at the top and an outlet funnel at the bottom of the plate, where a hanging drop is formed by a combination of capillary and surface-tension forces in which the tissue is formed. We present an implementation on a robotic liquid-handling device with a 96-multichannel pipette head, showing the same volumetric precision as in standard multi-well plates. this results in an excellent size uniformity of <10% for the microtissues. Finally, a whole screening process using four reference compounds was performed in comparison to classical monolayer cultures, underlining the different behavior of both cell-culture models. Based on the high flexibility of the microtissue production technology using either animal or human primary cells and cell lines, an efficient and automation-compatible technology will further accelerate the use of in vitro models in drug development. V-1-353 A novel platform for automated production and screening of scaffold-free, organotypic microtissues M. Drewitz 1, W. Moritz 1, J. Lichtenberg 1, C. Kasper 2 and J. M. Kelm 1 1InSphero AG, Zurich, Switzerland; 2leibniz University, Hannover, Germany