A Microfluidic System Combining Valve Automation and Spheroid Cultures to Characterize Hepatic Glucose Metabolism During Hormonal Stimulation

We describe an automated microsystem integrating hepatocyte spheroid culture and droplet-based bioanalysis modules. This device was shown to be suitable for long-term maintenance of primary hepatocytes. Importantly, this device was outfitted with microvalves to modulate composition of the input media with high temporal control. This ability was used to stimulate hepatocytes with waives of hormones, insulin and glucagon, so as to mimic physiological composition of hormones in the hepatic portal circulation. Using on-chip bioanalysis module we demonstrate that hepatocytes behave in physiological manner, consuming glucose upon stimulation with insulin and releasing glucose upon exposure to glucagon.