Elucidating the effects of microbubble pinch-off dynamics on mammalian cell viability.

ABSTRACT

In the biotechnology industry, ensuring the health and viability of mammalian cells, especially Chinese Hamster Ovary (CHO) cells, plays a significant role in the successful production of therapeutic agents. These cells are typically cultivated in aerated bioreactors, where they encounter fluid stressors from rapidly deforming bubbles. These stressors can disrupt essential biological processes and potentially lead to cell death. However, the impact of these transient, elevated stressors on cell viability remains elusive. In this study, we first employ /cgqamicrofluidics to expose CHO cells near to bubbles undergoing pinch-off, subsequently collecting and assaying the cells to quantify the reduction in viability. Observing a significant impact, we set out to understand this phenomenon. We leverage computational fluid dynamics and numerical particle tracking to map the stressor field history surrounding a rapidly deforming bubble. Separately, we expose CHO cells to a known stressor level in a flow constriction device, collecting and assaying the cells to quantify the reduction in viability. By integrating the numerical data and results from the flow constriction device experiments, we develop a predictive model for cell viability reduction. We validate this model by comparing its predictions to the earlier microfluidic results, observing good agreement. Our findings provide critical insights into the relationship between bubble-induced fluid stressors and mammalian cell viability, with implications for bioreactor design and cell culture protocol optimization in the biotechnology sector.