Real-time In-situ Lactate Monitoring in 3D Multi-cellular Spheroid Cultures by Using Enzyme-based Biosensors in Hanging Drop Networks

We present the integration of enzyme-based lactate biosensors into a microfluidic network of hanging drops, in which spherical microtissues can be formed and cultured over time. The addition of biosensors enables continuous in-situ monitoring of effects upon applying different culturing conditions or dosing compounds to the 3D tissue structures. The integration has been achieved by using a hybrid fabrication method, in which sensor modules on glass are embedded into a microfluidic PDMS structure. The lactate biosensors enabled real-time measurements of lactate produced by human colon carcinoma spheroids.