In this work, a bench-scale vacuum membrane distillation crystallization (VMDC) system coupled with microbubble aeration (MBA) was developed for treating high-salinity feed brine. Herein, the effect of seeding dose on membrane fouling and wetting control in the VMDC system was studied by using synthetic saturated calcium sulfate solution. The results showed that introducing gypsum seeds at a dose of 0.5 g/L effectively restricted membrane fouling and wetting. Subsequently, seeding-induced crystallization coupled with MBA was employed to investigate the control effect on membrane fouling and wetting during VMDC with simulated high-salinity feed brine treatment. As 0.5 g/L gypsum seeds were directly added at 7 h in the VMDC experiment while employing MBA, membrane fouling and wetting were effectively controlled. Finally, the mechanism behind the control of membrane fouling and wetting was elucidated during VMDC operation by integrating seeding-induced crystallization with MBA. This could be ascribed to the synergic effect of gypsum seeds and microbubbles in bulk solution. In brief, this work offers a promising approach to control membrane fouling and wetting during concentrating high-salinity wastewater by VMD.

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