Higher-order assemblies and aggregates of proteins strongly scatter light which can be used for determination of fibril stability . The analysis of stability curves determined by DLS or SLS can be cumbersome due to the large uncertainty in quantification of soluble monomers in samples with small amounts of large aggregates that dominate the scattering signal which consequently hinders correct normalization of the depolymerization curves. Moreover, aggregates that precipitate out of solution do not show any scattering signal (e.g. SH3 fibrils, Figure ). The Thioflavin-T (ThT) assay is an extensively used and popular method for quantification of fibrils, mostly in kinetic analysis of fibril formation, owing to its simplicity, throughput, and use of commonly available fluorescence plate readers. One of the main disadvantages of ThT-based (or other fluorescent probes such as ANS) detection is the great sensitivity of the fluorescence intensity of the dye towards solution conditions or structural features of the fibrils . DSF is an attractive method due to its high throughput and low sample consumption. However, it requires the presence of tryptophan residues localized such that their structural context within the protein changes between monomeric and fibrillar states and is accompanied by sufficiently large shift of its fluorescence spectrum . Unfortunately, tryptophan is a relatively rare amino acid and its introduction into the wild type by mutagenesis can affect the protein's free energy landscape, as demonstrated here in a case of αSyn (Figure a and b). The output of spectroscopic and scattering techniques reports only on relative concentrations of the species and the resulting data analysis requires making assumptions which might be incorrect. Specifically, the normalization of data may suffer from errors if the fibrils are partially dissociated in the absence of urea or not completely depolymerized in the highest urea concentration, where the relative monomer concentration is normalized to zero and one.