RT Journal Article SR Electronic T1 Rapid Fractionation and Characterisation of Alpha-Synuclein Oligomers in Solution JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.03.10.985804 DO 10.1101/2020.03.10.985804 A1 Arter, William E. A1 Xu, Catherine K. A1 Castellana-Cruz, Marta A1 Herling, Therese W. A1 Krainer, Georg A1 Saar, Kadi L. A1 Kumita, Janet R. A1 Dobson, Christopher M. A1 Knowles, Tuomas P. J. YR 2020 UL http://biorxiv.org/content/early/2020/03/14/2020.03.10.985804.abstract AB Oligomeric intermediates are implicated as neurotoxins in the pathogenesis of protein mis-folding diseases. Structural, biophysical and biochemical characterisation of these species is challenging due to their heterogeneous and transient nature, and their typically low abun-dance. Here, we show that microfluidic free-flow electrophoresis is capable of separating heterogeneous oligomer mixtures on a timescale of seconds, at least two orders of magnitude faster than conventional techniques. This enables analysis of oligomer structural heterogeneity, zeta-potential and immunochemistry with minimal sample perturbation under physiologically-relevant conditions.