Engineering a Microfluidic Liver-on-a-chip Platform and Cell-based Sensors

Abhinav Bhushan from Harvard Medical School

Tissue constructs that can mimic more closely an organ’s physiology are needed as platforms for drug discovery as well as to function as in vitro models of human diseases. Since liver plays a primary role in metabolism, the creation of physiological representations of the liver is especially desirable. I will present a simple method for adapting a double collagen gel configuration within a two-chambered perfusion microfluidic device. The cultures show stable albumin and urea secretions, as well as bile canalicular efflux and CYP450 activity for over several weeks. I will show that flow induced collagen synthesis results in higher function of hepatocytes cultured under flow over those in static cultures. I will share the strategy for development and long-term culture of a layered coculture of primary human hepatocytes with non-parenchymal cells that mimics the architecture of a liver sinusoid. I will share the development of cell-based and metabolic sensors that can be integrated with the microfluidic organ chip to obtain insights into dynamic cellular processes. The results indicate the development of an integrated microfluidic platform containing advanced tissue engineered constructs and sensors for exciting applications.