ISBN 9783843949187

978-3-8439-4918-7, Reihe Thermodynamik

Maximilian Wessner
A physically sound approach for the selection of optimized ATPS for purification of high-value biomolecules

193 Seiten, Dissertation Technische Universität Dortmund (2021), Softcover, A5

Zusammenfassung / Abstract

The industrial production of high-value biomolecules such as biopharmaceuticals or industrial enzymes has grown significantly within the last decades. A promising alternative to cost-intensive state-of-the-art chromatographic purification of these biomolecules is the aqueous two-phase extraction (ATPE) using an aqueous two-phase system (ATPS). Nevertheless, ATPE is not yet applied industrially, as state-of-the-art ATPS selection is based on trial-and-error screenings, leading to unoptimized ATPSs. As a result, product loss through aggregation/precipitation of the high-value biomolecule occurs.

Within this work, a physically sound approach, combining thermodynamic modeling and a small set of experiments, was developed. This approach allows for an identification of a tailor-made ATPS for the ATPE of a given high-value biomolecule with significantly lower effort than the state-of-the-art. It has been successfully demonstrated that the application of this approach enables a rapid and reliable selection of a tailor-made ATPS that provides high yield and low aggregation/precipitation of the biomolecule. To improve stability and solubility of the high-value biomolecule in the ATPS, excipients such as amino acids were considered and selected. The use of a suitable excipient further increased yield and minimized aggregation/precipitation of the biomolecule. To further optimize the approach and accelerate ATPS selection, ePC-SAFT was successfully applied to predict interactions and partitioning behavior of the high-value biomolecule in different ATPSs.

Prospectively, the results of this work will support the establishment of ATPE as purification technology for high-value biomolecules in industrial downstream processing.