Micro- and Nanotechnologies

SLAS2018 Innovation Award Finalist: Automating multi-tissue microphysiological systems using 3D microtissues

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  Olivier Frey, PhD

  Group Lead Technology & Platforms
  InSphero AG

The next step towards more biomimetic in vitro models is the design of multi-organ devices which allow communication of different tissue types. Combining physiologically relevant organ models in perfusion systems bears technological challenges and often leads to complicated culturing setups. Complex systems require trained personnel, reduce reproducibility and make integration into scalable routine processes difficult. The multi-tissue platform presented here builds on the European project "Body-on-a-Chip" and is developed in collaboration with ETH Zurich. Microfluidic channels and chambers were engineered for culturing of microtissue spheroids under physiological flow conditions. The platform has a plate-format, is produced completely out of polystyrene, and complies with SBS-standard dimensions. It includes 8 parallel channels, with each channel containing up to 10 microtissue compartments. The compartments have minimal dead volume (<2 uL) and are directly accessible with a robotic pipet tip for microtissue loading and retrieval. Open media reservoirs are located at both ends of each channel. Perfusion flow is generated through tilting the device back and forth on an automated system inside an incubator. Multiple devices can be operated in parallel increasing the number of conditions and statistical replicates executed in parallel. The concept allows on-demand interconnection of up to 10 same or different microtissues per channel in a very flexible way. With the broad range of available spheroid-based organ-models, a variety of pre-clinical testing applications can be generated using the very same platform. Using the system we, for example, were able to demonstrate that liver and islet microtissues showed significantly higher functionality under flow conditions compared to static culturing. The metabolic function of liver has been used to activate prodrugs and study their effect on tumor in liver-tumor co-cultures. Liver-islet interactions are currently investigated for metabolic disease models and investigate the influence of glucose-stimulated insulin secretion on liver metabolism.