Integrated microfluidic device to monitor unseen Escherichia coli contamination in mammalian cell culture

Microbial contamination in in vitro cell culture technologies is a common problem endangering the reliability of the collected data and biosafety of the biological products. Conventionally, microbial contamination can be detected by monitoring the pH and turbidity of cell culture media when using light microscope and/or molecular probes. These methods have limitations such as incompatibility with some cell lines, requirement for human intervention, and long experimental times. Here we present a new integrated microfluidic device (IMD) for the detection of the presence of Escherichia coli (E. coli) in benign prostatic hyperplasia (BPH-1) cell culture. Cell culture media acidity was monitored using an optofluidic sensor, and the cellular glucose metabolism using an electrochemical sensor having in-line continuous monitoring capability. Using this IMD, detection of a bacterial contamination at stages in which it is undetectable using a light microscope and plate counting methods is achieved. Additionally, since even the short-term (less than 8 h) presence of E. coli can change the cellular metabolism in the long term (at least up to 24 h), the use of non-invasive continuous cell culture monitoring platforms significantly reduce the risk of an undetected contamination, increasing the reliability of the conducted experiments with no interference to the cell culture process.