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Biological samples that are stable, monodisperse and that lack unfolded regions show a higher tendency to crystallize. However, it is not always possible to anticipate which samples will have these properties. A standard approach in structural biology projects consists in producing a number of sample variants for each single target originating from multiple constructs or from different species that are assayed for crystallization either sequentially or in parallel. This strategy has often proven successful. However, up-scaling protein production for a number of different samples requires manpower and time. For this reason, a significant amount of effort is often dedicated to identifying at an early stage those constructs or sample variants that are more likely to produce crystals. Fluorimetric thermal stability assays, also called Differential Scanning Fluorimetry (DSF) or Thermofluor assays, have been extensively used to identify ligands or buffer components that promote sample stability and increase crystallization success rate.