Wide‐surface pore microfiltration membrane drastically improves sieving decay in TFF‐based perfusion cell culture and streamline chromatography integration for continuous bioprocessing

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Abstract

Although several compelling benefits for bioprocess intensification have been reported, the need for a streamlined integration of perfusion cultures with capture chromatography still remains unmet. Here, a robust solution is established by conducting tangential flow filtration-based perfusion with a wide-surface pore microfiltration membrane. The resulting integrated continuous bioprocess demonstrated negligible retention of antibody, DNA, and host cell proteins in the bioreactor with average sieving coefficients of 98 ± 1%, 124 ± 28%, and 109 ± 27%, respectively. Further discussion regarding the potential membrane fouling mechanisms is also provided by comparing two membranes with different surface pore structures and the same hollow fiber length, total membrane area, and chemistry. A cake-growth profile is reported for the narrower surface pore, 0.65-µm nominal retention perfusion membrane with final antibody sieving coefficients ≤70%. Whereas the sieving coefficient remained ≥85% during 40 culture days for the wide-surface pore, 0.2-µm nominal retention rating membrane. The wide-surface pore structure, confirmed by scanning electron microscopy imaging, minimizes the formation of biomass deposits on the membrane surface and drastically improves product sieving. This study not only offers a robust alternative for integrated continuous bioprocess by eliminating additional filtration steps while overcoming sieving decay, but also provides insight into membranes' fouling mechanism.

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