Immunity-on-a-Chip: Integration of Immune Components into the Scheme of Organ-on-a-Chip Systems

Studying the immune system in vitro aims to understand how, when, and where the immune cells migrate/differentiate and respond to the various triggering events and the decision points along the immune response journey. It becomes evident that organ-on-a-chip (OOC) technology has a superior capability to recapitulate the cell-cell and tissue-tissue interaction in the body, with a great potential to provide tools for tracking the paracrine signaling with high spatial-temporal precision and implementing in situ real-time, non-destructive detection assays, therefore, enabling extraction of mechanistic information rather than phenotypic information. However, despite the rapid development in this technology, integration of the immune system into OOC devices stays among the least navigated tasks, with immune cells still the major missing components in the developed models. This is mainly due to the complexity of the immune system and the reductionist methodology of the OOC modules. Dedicated research in this field is demanded to establish the understanding of mechanism-based disease endotypes rather than phenotypes. Herein, we systemically present a synthesis of the state-of-the-art of immune-cantered OOC technology. We comprehensively outlined what is achieved and identified the technology gaps emphasizing the missing components required to establish immune-competent OOCs and bridge these gaps.