Miniaturization of aqueous two-phase extraction for biological applications: From micro-tubes to microchannels

Aqueous two-phase extraction (ATPE) is a biocompatible liquid-liquid (L-L) separation technique that has been under research for several decades towards the purification of biomolecules, ranging from small metabolites to large animal cells. More recently, with the emergence of rapid-prototyping techniques for fabrication of microfluidic structures with intricate designs, ATPE gained an expanded range of applications utilizing physical phenomena occurring exclusively at the microscale. Today, research is being carried simultaneously in two different volume ranges, mL-scale (microtubes) and nL-scale (microchannels). The objective of this review is to give insight into the state of the art at both microtube and microchannel-scale and to analyze whether miniaturization is currently a competing or divergent technology in a field of applications including bioseparation, bioanalytics, enhanced fermentation processes, catalysis, high-throughput screening and physical/chemical compartmentalization. From our perspective, both approaches are worthy of investigation and, depending on the application, it is likely that either (i) one of the approaches will eventually become obsolete in particular research areas such as purification at the preparative scale or high-throughput screening applications; or (ii) both approaches will function as complementing techniques within the bioanalytics field.