A simple method to determine evaporation and compensate for liquid losses in small-scale cell culture systems

Establish a method to indirectly measure evaporation in microwell-based cell culture systems and show that the proposed method allows compensating for liquid losses in fed-batch processes. A correlation between evaporation and the concentration of Na+ was found (R-2 = 0.95) when using the 24-well-based miniature bioreactor system (micro-Matrix) for a batch culture with GS-CHO. Based on these results, a method was developed to counteract evaporation with periodic water additions based on measurements of the Na+ concentration. Implementation of this method resulted in a reduction of the relative liquid loss after 15 days of a fed-batch cultivation from 36.7 +/- 6.7% without volume corrections to 6.9 +/- 6.5% with volume corrections. A procedure was established to indirectly measure evaporation through a correlation with the level of Na+ ions in solution and deriving a simple formula to account for liquid losses.