Real-time multi-analyte online monitoring of 3d cell cultures by integrated enzyme-based biosensors in hanging drop networks

We present the integration of enzyme-based lactate and glucose biosensors into hanging-drop networks. Hangingdrop networks are an ideal microfluidic platform for formation, cultivation, and continuous and long-term observation of 3D microtissues. The implementation of biosensors enables in-situ online monitoring of the effects of different culturing conditions and compound dosages on the microtissues. A hybrid approach including glass sensor modules embedded into a microfluidic polydimethylsiloxane (PDMS)-based chip facilitates system integration. The biosensors enable real-time recording of lactate production and glucose consumption of human colon carcinoma spheroids.