Microsensor in Microbioreactors: Full Bioprocess Characterization in a Novel Capillary-Wave Microbioreactor

Abstract

Microbioreactors (MBRs) with a volume below 1 mL are promising alternatives to established cultivation platforms such as shake flasks, lab-scale bioreactors and microtiter plates. Their main advantages are simple automatization and parallelization and the saving of expensive media components and test substances. These advantages are particularly pronounced in small-scale MBRs with a volume below 10 µL. However, most described small-scale MBRs are lacking in process information from integrated sensors due to limited space and sensor technology. Therefore, a novel capillary-wave microbioreactor (cwMBR) with a volume of only 7 µL has the potential to close this gap, as it combines a small volume with integrated sensors for biomass, pH, dissolved oxygen (DO) and glucose concentration. In the cwMBR, pH and DO are measured by established luminescent optical sensors on the bottom of the cwMBR. The novel glucose sensor is based on a modified oxygen sensor, which measures the oxygen uptake of glucose oxidase (GOx) in the presence of glucose up to a concentration of 15 mM. Furthermore, absorbance measurement allows biomass determination. The optical sensors enabled the characterization of an Escherichia coli batch cultivation over 8 h in the cwMBR as proof of concept for further bioprocesses. Hence, the cwMBR with integrated optical sensors has the potential for a wide range of microscale bioprocesses, including cell-based assays, screening applications and process development.