Quantifying the potential for bursting bubbles to damage suspended cells

Abstract

Bubbles that rise to the surface of a cell suspension can damage cells when they pop. This phenomenon is particularly problematic in the biotechnology industry, as production scale bioreactors require continuous injection of oxygen bubbles to maintain cell growth. Previous studies have linked cell damage to high energy dissipation rates (EDR) and have predicted that for small bubbles the EDR could exceed values that would kill many cells used in bioreactors, including Chinese Hamster Ovary (CHO) cells. However, it’s unclear how many cells would be damaged by a particular bursting bubble, or more precisely how much volume around the bubble experiences these large energy dissipation rates. Here we quantify these volumes using numerical simulations and demonstrate that even though the volume exceeding a particular EDR increases with bubble size, on a volume-to-volume basis smaller bubbles have a more significant impact. We validate our model with high-speed experiments and present our results in a non-dimensionalized framework, enabling predictions for a variety of liquids and bubble sizes. The results are not restricted to bubbles in bioreactors and may be relevant to a variety of applications ranging from fermentation processes to characterizing the stress levels experienced by microorganisms within the sea surface microlayer.

The Effects of Different Dynamic Culture Systems on Cell Proliferation and Osteogenic Differentiation in Human Mesenchymal Stem Cells

“…Despite bioreactors’ ability to improve mass diffusion and avoid hypoxia, the extensional flow can result in shear stress, causing cell damage [15]. Some types of bioreactors may also generate air bubbles during operation, and bubble bursting has been shown to cause injury to cells [16]. Similarly, turbulent hydrodynamics in the bubble–liquid interphase were found to cause cell damage in a sparged bioreactor [17].…”

Leachable‐Free Fabrication of Hydrogel Foams Enabling Homogeneous Viability of Encapsulated Cells in Large‐Volume Constructs

“…During this timeframe, excessive coalescence and/or bursting of air bubbles should be avoided, because it would not only lead to the obvious loss of the foam structure, as it has been directed correlated with cell death. [ 43 ] Therefore, two hydrogel foam conditions were explored in this work, namely: 1) F7s foams in which air bubbles were introduced into a GelMA+LAP solution with a syringe (1× aspiration/injection) and cells were added to this foam. After these steps one more air injection was made, and the foam was crosslinked for 7 s; and 2) F5s2s foams were produced through the addition of air bubbles to a GelMA+LAP solution (2× aspiration/injection) that was crosslinked for 5 s. After the first crosslinking step, cells were added, and the foams were exposed to UV light for 2 more seconds.…”

Clarifying the Tooth-Derived Stem Cells Behavior in a 3D Biomimetic Scaffold for Bone Tissue Engineering Applications

“…However, some bioreactors could promote hydrodynamic stress during cell culture resulting in shear stress, thus causing cell damage ( Tanzeglock et al, 2009 ). Some types of dynamic conditions may also generate air bubbles, and bubble–liquid interphase has shown to cause cells damages ( Walls et al, 2017 ). In this context, dynamic culture systems, such as spinner flasks, are widely used due to their ability to improve mass transfer in cell cultures suspension.…”