Flip-Flow bioreactors enhance bioproductions with better oxygen transfer and energy saving.

A flip-flow bioreactor featuring clock- and counter-clockwise stirring was used to enhance oxygen transfer efficiency and mixing performance for high-density aerobic cell growth. Computational fluid dynamics (CFD) simulations demonstrated that bidirectional stirring significantly improved dissolved oxygen concentration, gas distribution uniformity with better oxygen mass transfer coefficient (kLa) compared to conventional unidirectional stirring. Extremophile Halomonas bluephagenesis was engineered for production of single-cell protein (SCP), poly(3-hydroxybutyrate) (PHB), and gamma-aminobutyric acid (GABA) in the flip-flow bioreactor, respectively, achieving higher cell dry weight (CDW) and product synthesis compared to the regular bioreactor, even though growth was conducted under reduced aeration rates and at lower agitation speeds in the flip-flow bioreactor. Specifically, the SCP and PHB were increased by 36.8% (98.1 g/L vs. 71.7 g/L in the control) and by 25.4% (101.7 g/L vs. 81.1 g/L in the control), respectively. The GABA production strain increased its CDW by 51.1%, reaching 68.3 g/L vs. 45.2 g/L of the control, enabling the highest reported GABA synthesis of 1708.8 g/L. The flip-flow bioreactor demonstrates superior oxygen transfer efficiency and significant energy-saving for aerobic bioproductions.