Aqueous Two‐Phase Systems at Large Scale: Challenges and Opportunities

Aqueous two‐phase systems (ATPS) have proved to be an efficient and integrative operation to enhance recovery of industrially relevant bioproducts. After ATPS discovery, a variety of works have been published regarding their scaling from 10 to 1000 L. Although ATPS have achieved high recovery and purity yields, there is still a gap between their bench‐scale use and potential industrial applications. In this context, this review paper critically analyzes ATPS scale‐up strategies to enhance the potential industrial adoption. In particular, large‐scale operation considerations, different phase separation procedures, the available optimization techniques (univariate, response surface methodology, and genetic algorithms) to maximize recovery and purity and economic modeling to predict large‐scale costs, are discussed. ATPS intensification to increase the amount of sample to process at each system, developing recycling strategies and creating highly efficient predictive models, are still areas of great significance that can be further exploited with the use of high‐throughput techniques. Moreover, the development of novel ATPS can maximize their specificity increasing the possibilities for the future industry adoption of ATPS. This review work attempts to present the areas of opportunity to increase ATPS attractiveness at industrial levels. There is a lack of inclusion of aqueous two‐phase systems (ATPS) into industrial‐scale bioprocesses, although there is a large amount of research at laboratory or pilot‐scale. To changes, the present review discusses large‐scale considerations of ATPS operation and different strategies to maximize their attractiveness, such as high‐throughput screening and optimization techniques, different phase separation strategies, novel bioprocess modeling on ATPS‐based processes and economic analyses, research the removal of ATPS components after separation and recycling of phase forming chemicals and the application of novel ATPS types.