“…Despite the high selectivity, high resolution and high purity of the product, chromatography also exhibits some limitations, namely low associated throughputs, low proteolytic and chemical stabilities when biological ligands are used, high scale pressure drops, time-consuming nature, and high costs, which hinder the production of biopharmaceuticals at low cost ( Rosa et al, 2010 ; Jozala et al, 2016 ; Castro et al, 2019 ; Castro et al, 2020 ). To surpass these limitations, research has focused on the development of chromatographic ligands with enhanced selectivity, robustness, and reproducibility ( Martins et al, 2014 ), as well as on non-chromatographic strategies, such as affinity precipitation ( Hoffman et al, 2001 ; Roque et al, 2007 ), preparative electrophoresis ( Thomas et al, 2002 ), high-performance tangential flow filtration ( Lazarova et al, 2001 ), membrane filtration ( Castilho et al, 2002 ), precipitation ( dos Santos et al, 2017 ), aqueous biphasic systems ( Zijlstra et al, 1998 ; Azevedo et al, 2009 ), non-chromatographic magnetic separation ( Karl and Schwa, 2005 ), high-gradient magnetic separation ( Akgo et al, 2004 ; Gomes et al, 2018 ), and crystallization ( dos Santos et al, 2017 ). Nevertheless, the progress made in this field is still far from that required, and downstream processing continues to account for the most expensive part of biomanufacturing ( Azevedo et al, 2009 ).…”