Cell damage in sparged mammalian bioreactors: Which sources of shear are implicated in causing injury to sensitive animal cells during aerated culture?

Introduction:
Mammalian and other shear-sensitive cells are vulnerable to hydrodynamic stresses in aerated bioreactors. Recognizing the multiple loci of damaging shear helps engineers select gentler gas transfer strategies (e.g., larger bubbles, perfusion with micro-spargers, or bubble-free aeration systems).

Given Data / Assumptions:

• Aerated (sparged) culture with gas bubbles rising to the surface.
• Presence of free surface where bubbles burst and form foam.
• Cells are non-cell-wall organisms with delicate membranes.

Concept / Approach:
Injurious shear arises in three main regions: the turbulent bulk due to mixing and bubble wakes; the free surface where bubble rupture creates transient, high-strain microjets and capillary waves; and the foam layer where films thin and bubbles interact, creating localized shear between interfaces. All contribute to cell damage risk.

Step-by-Step Solution:
Identify bulk mixing as a source: eddies and bubble wakes impose fluctuating shear on cells.Identify surface rupture: bursting bubbles generate rapid film retraction and microjets.Identify foam shear: bubble–bubble interactions and film drainage strain cells trapped near the surface.Conclude that all listed sources can cause damage.

Verification / Alternative check:
Lowering gas flow, adding shear protectants (e.g., Pluronic F-68), using headspace overlay instead of vigorous sparging, or employing micro-porous spargers with controlled bubble size all reduce cell lysis, consistent with multiregion shear mechanisms.

Why Other Options Are Wrong:
Any single source alone underestimates the combined impact observed in practice.

Common Pitfalls:

• Blaming only impeller shear while ignoring surface phenomena.
• Assuming antifoam always helps; it can alter kLa and may have mixed effects on cell health.

Final Answer:
All of the above