Design and Characterization of a 3D-Printable Membrane Aeration Module for Small-Scale Bioprocess Prototyping

Oxygen transfer is a critical design parameter in laboratory-scale bioprocess systems used for prototyping, process development, and scale-down studies of mammalian cell cultures, particularly when cultivating shear-sensitive mammalian cells. In this work, we present the design and characterization of a 3D-printed modular, membrane-based aeration module that enables bubble-free oxygen transfer in laboratory reference cell-cultivation systems. The aeration module was developed as an external, small-scale unit intended for flexible integration into laboratory bioreactors and perfusion setups. Fabricated via fused deposition modeling, the final design features a three-chamber membrane-stacking architecture that ensures mechanical stability, tightness, and biocompatibility, while allowing for straightforward adaptation through editable CAD files. The system was experimentally evaluated with respect to oxygen transfer performance under varying relative liquid flow rates and membrane configurations (PTFE and PVDF), each with two different pore sizes (0.22 µm and 0.45 µm). Key performance parameters of the aeration module were determined and include dissolved oxygen (DO) profiles, volumetric oxygen transfer coefficients (7.26 h^-1), oxygen transfer rates (OTRs) (max. 61.4 mg L^-1h^-1), and the pressure-normalized oxygen mass transfer rate (0.87 g m^{- 2}bar^{- 1}h^{- 1}). Overall, the modular design and quantified performance provide a versatile tool for rapid iteration and evaluation of membrane-based oxygenation strategies in early-stage bioprocess development.