This project will significantly enhance bioreactor product Mty by significantly increasing the bubbleless oxygen delivery to bioreactors. Sales of major biopharmaceuticals currently exceed $18 billion. Oxygen limitations often control cell growth and viability and therefore product titer. Sparging is extensively used to oxygenate fermentation broths using additives (e.g. Pluronic compounds) to 3rotect cells from shear. High gas transfer membranes provide a practical alternative to sparging, reducing product purification steps and allowing increased cell densities and product titer. To date, non-porous silicone rubber tubing provides limited oxygen enhancement while occupying much volume. Hydrophobic microporous membranes, while working well initially, quickly wet out or have cells grow into the pores and dramatically reduce flow. We propose using a novel family of non-porous perfluorinated hollow fiber membranes to dramatically enhance bioreactor oxygenation. We propose an innovative structure using a novel high gas flux non-porous perfluoromembrane coating to provide the needed wet-out resistance and high gas flux on top of a porous support. By doing this we can optimize the porous support and overall system for high flux or steam sterilization in combination with wet-out resistance. The non-porous perfluorinated nature of CMS membranes suggests that wet-out and cells growing into the support should not be an issue. In this Phase I program we will: a) fabricate hollow fiber membrane modules with CMS perfluorinated membranes, b) evaluate their oxygen delivery capability to both bioreactor broth and actual cell cultures, c) demonstrate enhanced growth of both cells and hybridoma, and d) demonstrate enhanced oxygen delivery to bioreactors and e) demonstrate a steam sterilizability non-wetting hollow fiber system. Economic evaluation will also be done to determine overall value of membrane oxygenators.
