Temperature-responsive chromatography for bioseparations: A review

Abstract In recent decades, in addition to existing small-molecule drug therapies, biomedical technology has also rapidly progressed, leading to the development of various therapies based on biopharmaceuticals and therapeutic cells. However, these materials require effective separation methods for their analysis and production. A representative separation method, which has been extensively studied, is the temperature-responsive chromatography system using poly(N-isopropylacrylamide) and its copolymers. Over the last 20 years, various temperature-responsive chromatographic techniques have been developed for the separation of different types of analytes by changing the copolymer composition, the polymer graft configuration, and the base materials of the stationary phase. The developed methods have been successfully applied for the separation of small-molecule drugs, peptides, and proteins, without affecting their biological activity, simply by changing the column temperature. Furthermore, temperature-modulated cell separation columns have been investigated for the separation of cells without changing their properties. Therefore, the developed methods can serve as effective tools for the current and future bioseparation of various biological compounds, biopharmaceutical proteins, and therapeutic cells that are currently used in therapies.