Abstract

There are a wide variety of tools available within drug discovery from in silico mathematical prediction models, through high throughput screens, in vivo animal models and advanced in vitro 3D organ-on-a-chip models, otherwise known as microphysical systems (MPS). MPS are microfluidic devices capable of mimicking human biology in vitro at the smallest biologically acceptable scale, defined by a context of use. They perfuse individual organ models and connect multi-organ models together into systems, the latter of which opens up areas previously only addressed by animal models. Models are built from multiple human cell types to closely represent human physiology. Here we will discuss how we have developed specific contexts of use for single-and multi models, including the evaluation of therapeutics for chronic liver disease, to assess inflammatory-mediated toxicity and predict human bioavailability of oral exposed compounds. For all assays a range of translationally/ clinically relevant endpoints are utilised to ensure the MPS models provide the highest in vivo relevance to help reduce drug attrition in the clinic.