Understanding cell growth is critical for developing efficient and robust bioreactor processes. Due to exponential growth characteristics, small perturbations in process conditions such as inoculation density, media composition, and pH can have large impacts on cell density and process performance. In addition, standard offline measurement techniques fail to capture important data such as the exact density and timing of peak cell growth. This makes process decisions based on cell density, such as temperature shifting, difficult to time. Online capacitance probes offer unique opportunities to understand and control mammalian cell culture processes in real time.<br/><br/>This study demonstrates techniques to precisely control cell growth, as measured through online capacitance probes, by modulating reactor temperature. Reactors were equipped with online dielectric capacitance probes, which correlate electrical permittivity with biomass density. Near continuous feeding strategies were used to avoid major perturbations in the capacitance. Biomass measurements from the probe were compared to a pre-determined growth curve selected by the experiment operator. A temperature control loop was then used to adjust the growth rate of the cells to match the pre-determined growth curve. This allowed precise control of cell growth from inoculation to peak viable cell density.<br/><br/>Several applications of this technique will also be discussed. Identical bioreactors can be controlled to peak at distinct times separated by a full day, or at distinct densities. These different growth curves can be analyzed to optimize cell culture conditions. We will also show how such a technique can be used to minimize the impacts of process variability. Multiple bioreactors inoculated over a wide range of densities, were controlled to peak at the same time and cell density. These results demonstrate new opportunities to improve mammalian process performance through more precisely controlled experimental designs and increased robustness in the face of process variability.

Online capacitance probes precisely control cell biomass growth through temperature regulation

253rd National Meeting (2017)

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