Gut-on-Chip microphysiological systems: Latest advances in the integration of sensing strategies and adoption of mature detection mechanisms

Synergic efforts in microfabrication processes, cells culture and tissue engineering promoted extraordinary progress in Organ-on-Chip (OoC) technology, leading to the development of in vitro microphysiological models able to recapitulate the microenvironment and key biochemical, functional, structural and mechanical features of specific tissues and living organs. In order to assess the functionality of these cell cultures with every increasing biological complexity, it is also important to equip OoCs with miniaturized sensing devices able to monitor key physical and chemical parameters related to the culture microenvironment and to pathophysiological cell-cell interactions. Gut is one of the most interesting and studied human organs: it performs multiple fundamental body functions, from transport, absorption and metabolism of nutrients and drugs, to the maturation of the immune system and host protection from pathogens and infections. In this Review, an overview of Gut-on-Chip (GoC) systems is provided, with a special attention focused on the most relevant sensing strategies integrated into GoC, aimed at monitoring in situ the microphysiological parameters related to intestine functionalities. Advantages and limitations associated with currently integrated physical, chemical, and biochemical sensors are discussed, together with the challenges that the technology still faces, and the possible adaptive solutions coming from other developed OoC models. Finally, we focus the attention on how gut microbiota connect to other organs of the human body and on the role of gut in the understanding of the progression of many diseases, such as the most recent pandemic infection caused by SARS-CoV-2 virus.