Sensing of Oxygen Concentration in a Microfluidic Device mimicking Liver 3D Microarchitecture

Abstract

International audienceWe designed a microfluidic structure which closely reproduces liver microarchitecture, constraining primary rat hepatocytes at a high density and in three dimensions (3D), and in which a gradient of oxygen can be generated. The device includes an oxygen sensitive membrane that could map the oxygen consumption of hepatocytes. INTRODUCTION Compared to classical two-dimensional cell culture, microfluidic devices or/and 3D culture conditions were evidenced to increase the period of time during which primary hepatocytes retain their functions [1]. Moreover, microfluidic techniques offer the opportunity to mimic the in vivo hepatocyte zonation, by subjecting hepatocytes to oxygen gradients [1-2]. Such oxygen gradients that can be estimated by numerical simulations, were recently experimentally assessed using an oxygen sensitive fluorescent membrane [3]. We proposed to include the oxygen sensitive membrane within a miniaturized fluidic device mimicking several hepatic cords in series, and inducing a gradient of oxygen on those. Moreover each of those hepatic cord units was inducing 3D organization of hepatocytes, due to the 72 µm height of culture chambers in which they can aggregate