Optical sensor-based systems for the analysis of cell metabolism and bioenergetics

A deep understanding of mammalian cell metabolism and bioenergetics, and their alterations in disease states, is essential for many areas including cell biology, medicine, pharmacology, drug development and biotechnology. New sensor based systems and applications have enabled major advancements in this field, and they continue to develop and spread rapidly. Here we review the current analytical systems for the assessment of cell metabolism that rely on optochemical O₂, pH and CO₂ sensors. We describe the main operational principles of the sensors, analytical readouts that report on the key metabolic pathways (mainly glycolysis, the OxPhos and TCA cycle), and the corresponding sensing formats and platforms for measuring fluxes of cellular glycolysis, the OxPhos and the TCA cycle. Exemplary metabolic assays performed on these sensing platforms are also provided, explaining the data they generate. Finally, merits and limitations of current sensor-based systems and applications are discussed, highlighting potential avenues of their further development.