(63e) Clarence G. Gerhold Award Lecture:  Flexibility-Based Separations – a New Paradigm for Membranes

Membrane systems have been designed for separations based on both size and solubility (e.g., partitioning). The size-based separations dominate in ultrafiltration processes used for the concentration and purification of proteins. However, there is also considerable interest in using membrane systems for the separation of large flexible biomolecules like DNA and PEGylated proteins (proteins with attached polyethylene glycol chains). The behavior of these biomolecules is considerably more complex, with the elongational flexibility playing a critical role in their ultrafiltration characteristics. This talk examines experimental data for DNA transmission demonstrating the importance of flow-induced elongation on the ultrafiltration behavior. Results show how differences in elongational flexibility can be exploited for the separation of topological isoforms of the DNA, with a linear isoform having much greater transmission than a supercoiled isoform with the same base-pair sequence. It is also possible to design novel membranes to enhance the separation by pre-stretching the DNA. These results provide the first quantitative demonstration of a flexibility-based separation using membrane ultrafiltration.