Advances in in situ and in-line liquid-liquid extraction for bioprocess intensification

Liquid-liquid extraction (LLE) has been commonly used to purify products downstream in bioprocesses. LLE can be operated in different modes. We specifically focus on two modes: (1) in situ and (2) in-line. For the in situ mode, LLE occurs simultaneously with fermentation inside a fermenter. For the in-line mode, LLE occurs in an external extraction unit that is separate from a fermenter. These two modes can intensify the bioprocess and enhance productivity typically by the continuous removal of inhibitory species. In this review, we provide a summary of applications for these two modes, particularly highlighting their roles in bioprocess intensification. Advances in equipment and process designs for each mode will also be discussed, along with key examples.