Progress in the Development of Aqueous Two-Phase Systems Comprising Ionic Liquids for the Downstream Processing of Protein-Based Biopharmaceuticals

摘要

The advent of biopharmaceuticals in modern medicine has brought enormous benefits to treat chronic and life-threatening diseases while improving the well-being of humans. Proteins (including antibodies) represent a large fraction of the biopharmaceuticals market, but are still amongst the costliest options due to the lack of cost-effective purification techniques. The most relevant strategies in the downstream processing of protein-based biopharmaceuticals are the highly selective nature of chromatographic techniques, which however, present some drawbacks including the difficulty to apply in large scale due to batch processing, large scale pressure drops, low chemical and proteolytic stability, and high cost.2 To overcome such limitations, alternative downstream processes have been proposed, such as aqueous two-phase systems (ATPS). These systems were initially proposed by Albertsson in the mid 1950s as an alternative to traditional liquid-liquid extraction techniques,3 consisting of two immiscible aqueous-rich phases that separate above given concentrations, being one aqueous phase enriched in one of the solutes while in the other phase the second component prevails." An overview of the application of ATPS for the purification of proteins is represented in Figure 1, being additionally illustrated a typical ATPS ternary phase diagram in an orthogonal representation, in which the water concentration is not shown (pure water becomes the origin of the orthogonal axes, corresponding to the amount required to reach 100 wt% in a given mixture composition).