Bubble-induced fluid stresses and viability changes in nearby mammalian cells

A living cell, when subjected to a high fluid stress, can have key biological processes disrupted, potentially leading to cell death. In the biotechnology industry the mammalian CHO cell is grown in aerated tanks where locally elevated stresses - created by bubbles rapidly deforming during rupture, coalescence, or pinch-off - can be high enough to kill nearby cells; however the effect of elevated stresses on cells at the timescales of these bubble events is unclear. Here we investigate the effect on cell viability from fluid stresses created by a bubble undergoing topological change, using a combination of computational fluid dynamics (CFD), numerical particle tracking, and microfluidics. CFD and particle tracking are employed to unlock the stress field history in the fluid surrounding a deforming bubble. In a microfluidic device CHO cells are injected near to a rapidly rearranging bubble, with the cell's motion captured using high-speed optical microscopy. Using this approach, we predict mortality on a cell-by-cell basis, eliciting an overall bubble-induced effect on a cell population's viability. We believe this work will be especially pertinent in the biotechnology sector, guiding bioreactor design and the optimization of cell culture protocols.