An organ-on-a-chip is a microfluidic cell culture typically made of continuously perfused chambers inhabited by living cells arranged to simulate tissue- and organ-level physiology. Conventional 2D or 3D culture systems do not allow to reach the levels of tissue and organ funtionality that these devices are capable to through the recapitulation of multicellular architectures, tissue-tissue interfaces, physicochemical micro-environments and vascular perfusion of the body. The development of the microfluidic devices described in this thesis is mainly concerns about organotypic cultures of spheroids made by primary humanhepatocyte PHH, and their interaction with other cell cultures as gut, pancreas, fat and muscles. This thesis is divided into two major parts.