Real-time monitoring of cell culture contamination via TVOC and gas sensing technologies

In vitro human cell cultures are indispensable in pharmaceutical preclinical research. However, they are vulnerable to bacterial contamination, which can compromise the integrity of the experiment. Therefore, avoiding contamination in the first place or at least detecting contamination early to avoid further contamination is crucial. This feasibility study continuously monitored bacterial emissions of volatile organic compounds for early contamination detection. We used individual semiconductor-based sensors for total volatile organic compounds (TVOC), ammonia, and hydrogen sulfide to directly detect bacterial contamination inside the cell culture incubator. Staphylococcus aureus contaminated (N = 1), Staphylococcus epidermidis contaminated (N = 1), and non-contaminated human cell cultures (N = 2) were tested one after the other, and the development of their emission levels was recorded. The recorded TVOC, ammonia, and hydrogen sulfide levels were then analyzed to determine if they could be used as a predictor of cell contamination within a 2-hour time window from the onset of contamination. As a result, measurements of ammonia and hydrogen sulfide were inconclusive. Even if further research is required to refine the sensitivity and specificity of TVOC-level analysis, this study highlights the potential of TVOC sensors for detecting bacterial contamination. This work forms the basis for developing non-invasive, real-time monitoring systems. Such systems ensure the sterility and quality of cell culture practices during cell culture development inside the incubator, not only afterward. Real-time TVOC monitoring can ultimately support the scalability and efficiency of drug development processes without human intervention for contamination monitoring.