Optimization of Bacterial Cell Culturing by Multiphysics Modeling

Abstract

Bacteria are often used as host cells for the propagation of plasmid DNA and recombinant proteins for applications in bioprocess, biomedical, and genetic engineering and biochemistry. To ensure that only bacteria of interest are growing, the solid media (i.e., agar) is sterilized at 121°C and prepared in the presence of specific quantities of particular antibiotics during cooling. The cooled temperature at which the antibiotic is added to the media is crucial due to the propensity of thermal degradation. Typical approaches to addressing this issue fail to incorporate cooling environments, and direct measurement can pose contamination risks. A time dependent study of the heat transfer from sterilized media in the heated vessel to the environment has been conducted in COMSOL Multiphysics, coupling the kinetics of the thermal degradation of ampicillin or penicillin to viable antibiotic concentration. In effect, an optimal time to add the antibiotic is predicted. The vessel used to prepare agar is modeled as a beaker, and temperatures are predicted as the simulated agar cools to room temperature after which an average volume temperature and the final expected concentration of viable antibiotics over time are determined. The ease of determining accurate cooling times for agar preparation will allow for more precise concentrations of antibiotic in the agar, thus allowing for better experimental control in the quality and yield of product obtained from cell/bacteria cultures.