Human immunocompetent microfluidic platform for in vitro testing in immuno-oncology applications

In vitro evaluation of novel therapeutic approaches often fails to reliably predict efficacy and toxicity, especially when recapitulating conditions involving recirculating cells. Current testing strategies are often based on static co-culturing of cells in suspension and 3D tissue models, where cell sedimentation on the target tissue can occur. The observed effects may then mostly be a consequence of sedimentation and of the corresponding forced cell-tissue interactions. The realization of continuous medium flow helps to better recapitulate physiological conditions. To tackle current limitations of perfused organ-on-chip approaches, we developed a microfluidic chip and operation concept, which prevents undesired sedimentation and accumulation of cells in suspensions over multiple days by relying on gravity-driven perfusion. Our platform, which we termed “human immune flow (hiFlow) chip”, enables to co-culture cells in suspension with up to 7 preformed microtissue models. The primary goal was to study flow-dependent recruitment of the circulating cells to the different tissue spheroids. Cells and tissues could be monitored on-chip via high-resolution microscopy, while cell suspensions and microtissues could be easily retrieved for off-chip analysis. Our results demonstrate that primary immune cells and spheroid models of healthy and diseased tissue can be maintained for over 6 days on chip. As proof-of-principle assay, we investigated the efficacy of antibody treatment against diffuse midline glioma, a highly aggressive pediatric tumor. We believe that our platform will help to increase the prediction power of in vitro preclinical testing of novel immunotherapeutics.