A novel membrane stirrer system enables foam‐free biosurfactant production

Abstract

Bioreactors are the operative backbone, for example, for the production of biopharmaceuticals, biomaterials in tissue engineering, and sustainable substitutes for chemicals. Still, the Achilles' heel of bioreactors nowadays is the aeration which is based on intense stirring and gas sparging, yielding inherent drawbacks such as shear stress, foaming, and sterility concerns. We present the synergistic combination of simulations and experiments toward a membrane stirrer for the efficient bubble-free aeration of bioreactors. A digital twin of the bioreactor with an integrated membrane-module stirrer (MemStir) was developed with computational fluid dynamics (CFD) studies addressing the determination of fluid mixing, shear rates, and local oxygen concentration.Usability of the MemStir is shown in a foam-free recombinant production process of biosurfactants (rhamnolipids) from glucose with different strains of Pseudomonas putida KT2440 in a 3-L vessel and benchmarked against a regular aerated process. The MemStir delivered a maximal oxygen transfer rate (OTR max ) of 175 mmol L −1 h −1 in completely foam-free cultivations. With a high space-time yield (STY) of 118 mg RL L −1 h −1 during a fed-batch fermentation, the effectiveness of the novel MemStir is demonstrated. Simulations show the generic value of the MemStir beyond biosurfactant production, for example, for animal cell cultivation.

High-quality physiology of Alcanivorax borkumensis SK2 producing glycolipids enables efficient stirred-tank bioreactor cultivation

“…To circumvent these challenges, batch fermentations with bubble aeration and bubble-free membrane aeration were performed using acetate as the carbon source. As shown in other publications with other microorganisms and cell lines, the batch fermentation with bubble-free membrane aeration showed no foam formation, so antifoaming agent addition was unnecessary ( Frahm et al, 2009 ; Coutte et al, 2010 ; Bongartz et al, 2021 ; Bongartz et al, 2023 ).…”

“…One disadvantage is biofilm formation on the membrane by A. borkumensis . However, this could possibly be further reduced with a dynamic membrane module, for example, the membrane stirrer by Bongartz et al (2023) , as this significantly increases the flow velocity and the shear rate of the membrane module and thus makes biofilm formation less likely.…”

“…Various approaches can be employed to mitigate foam formation in fermentation processes, such as adding antifoaming agents or utilizing mechanical foam breakers. Alternative approaches to foam prevention include in situ liquid-liquid extraction ( Demling et al, 2020 ; von Campenhausen et al, 2023 ), foam fractionation ( Blesken et al, 2020 ; Koop et al, 2020 ; Oraby et al, 2023 ), defoamers as substrates ( Sha et al, 2012 ; Bator et al, 2020 ), pressurized headspace aeration ( Weiser et al, 2022 ), and bubble-free membrane aeration ( Bongartz et al, 2021 ; Bongartz et al, 2023 ).…”

Optimized Feeding Strategies for Biosurfactant Production from Acetate by Alcanivorax borkumensis SK2

“…However, one challenge encountered during extended feeding was the increased difficulty in controlling foam formation as the process progressed. To address this issue, bubble-free aeration with an in situ membrane module was considered in this study as a potential solution [62,63]. Membrane aeration provides growth conditions similar to bubble-aerated processes but with the advantage of eliminating foaming.…”

“…It also harbors risks such as blocking sterile filters, which cause overpressure and endanger sterility [58][59][60]. Researchers got creative to mitigate foam formation in fermentation processes, such as using antifoaming agents [61], bubble-free membrane aeration [62,63], defoamers as substrates [64,65], foam fractionation [66,67], headspace aeration in combination with overpressure [68], in situ liquid-liquid extraction [69], and mechanical foam breakers [70]. Among all the strategies mentioned, bubble-free membrane aeration changes the process minimally, as it can be carried out in the same way as with bubble aeration but without the addition of antifoaming agents or solvents for in situ extraction.…”