PT - JOURNAL ARTICLE AU - Arter, William E. AU - Xu, Catherine K. AU - Castellana-Cruz, Marta AU - Herling, Therese W. AU - Krainer, Georg AU - Saar, Kadi L. AU - Kumita, Janet R. AU - Dobson, Christopher M. AU - Knowles, Tuomas P. J. TI - Rapid Fractionation and Characterisation of Alpha-Synuclein Oligomers in Solution AID - 10.1101/2020.03.10.985804 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.03.10.985804 4099 - http://biorxiv.org/content/early/2020/03/14/2020.03.10.985804.short 4100 - http://biorxiv.org/content/early/2020/03/14/2020.03.10.985804.full 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.