Measurement of respiration and acidification rates of mammalian cells in thermoplastic microfluidic devices

Abstract

Abstract Luminescent chemical sensors have been proven to be a valuable asset in cell cultures and generally in microbiological studies. We present microfluidic cell culture devices with integrated optical chemical sensors. The integrated sensors offer the possibility to monitor dissolved oxygen and pH levels and enable the measurement of respiration and acidification rates. The cell metabolism was observed using this method by temporarily stopping the incubation flow, barely influencing the cell culture. A thermoplastic polymer is used as oxygen impermeable chip material to enable the measurement of respiration rates, which is not possible with widely used PDMS-based microfluidics. Hence, an innovative fast prototyping strategy is utilized to enable the replication of small series of thermoplastic microfluidic chips. We were able to demonstrate the suitability of this measurement method by monitoring the metabolic response of a human lung carcinoma epithelial-like cell line (A549) to the exposure of FCCP (Carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone), a drug known for its up-regulating effect on respiration and acidification rates. This universal measurement approach can potentially be deployed in all sorts of microfluidic devices and help to retrieve valuable data from inside those systems beyond classical end-point detection methods. It therefore complements modern 3D cell cultures and organ-on-chip research with a powerful analytical technology for gathering information about ongoing cell metabolism.