Abstract

Emulating Organ-Organ Interaction Using Scalable Microfluidics and Multi-Cellular Spheroids

Olivier Frey, Head of Technology and Platforms, InSphero AG

Over the past years, we have developed the different technical and biological components ultimately merging into a scalable microfluidic multi-organ platform applicable for a broad spectrum of pre-clinical studies. An example we are currently advancing is a microphysiological 3D human liver – islet microtissue platform, that enables direct liver – pancreas crosstalk and a better understanding of metabolic diseases. We use 3D spheroids as biological organ models. They have become one of the most frequently used 3D cell culture systems in research and pharmaceutical industry, mainly due to their reasonable balance between physiological relevance and experimental complexity. The liver model consists of a primary Hepatocyte – Kupffer – Stellate cell triple-culture with preserved metabolic and inflammatory function over at least four weeks. Islet microtissues comprise all endocrine cells at physiological ratio and remain glucose responsive over the same duration. Both models are combined in microfluidic culturing device enabling interconnecting of up to ten 3D spherical microtissues. The microfluidic platform meets the requirements for scalability through the use of an injection-molding mass-fabrication process and a gravity-driven tubeless flow concept, which enables parallelization. Large-scale multi-tissue experiments are enabled with a fast and reliable method for loading of quality-controlled spheroids using a fully automated robotic pick-and place-transfer.