Albena Lederer^1,2, Susanne Boye¹, Martin Geisler¹, Upenyu Muza^1,2

¹Center Macromolecular Structure Analysis, Leibniz-Institut für Polymerforschung Dresden e.V., Hohe Str. 6, 01069 Dresden, Germany

²Department Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, Matieland 7602, South Africa

Field flow fractionation (FFF) has been known since the 1960s as a technique that can separate a wide range of particle sizes. It has proven to be a well-suited alternative to size exclusion chromatography when dealing with sub-µm particles and delicate structures that are sensitive to interactions with column material or shear forces.

Recent developments show that FFF opens almost unlimited possibilities for characterizing very complex macromolecular architectures, self-assemblies, their responsiveness to external stimuli, polymer networks, polymer bioconjugates or drug delivery systems. Flexible adjustment of separation conditions by varying the flow, separation force, and channel type, multiplied by the number of possible detectors - dynamic and static light scattering, UV-Vis, viscosity, refractive index, etc. - expands the possibilities of obtaining maximum information about these materials in a single run of a few µg.

Variation of the FFF mode of separataion in combination with multiple detectors and a profound physical interpretation of the separation theory and structural parameters allow to obtain maximum information from the separation experiments. Application of these theoretical considerations to real systems such as polymersomes and exosomes, bioconjugates, polymer-drug conjugates, hyperbranched and crosslinked polymers, single-chain nanoparticles, and ionic macromolecules provides qualitative and quantitative insights into conformation, charge location, size distribution, and reactivity and answers a number of open questions about advanced polymer systems.