As the focus of biological research expands beyond traditional enzymatic activities, protein apparent thermal stability has become an important generalizable read-out for protein biochemical states. Differential Scanning Fluorimetry (DSF) is a method which uses an environmentally sensitive dye, typically SYPRO Orange, to determine the apparent thermal melting temperature (Tma) of a purified protein. DSF is used widely across disciplines, from high throughput ligand discovery to buffer optimizations for structural biology. However, widespread protein incompatibilities with both the dyes and analyses for DSF left applications severely limited. Here, we share the discovery of over 100 novel dyes, updated theoretical models, and improved analyses methods for DSF. These discoveries achieve the flexibility necessary to adapt DSF to diverse proteins on demand, increasing protein compatibility from 29 to 94% of proteins. By providing the dye library and analyses alongside efficient approaches to select among them for a given protein, this work expands the functionality of DSF without compromising its ease and efficiency. The dye library is termed “Aurora”, the updated analyses “DSFworld”, and the expanded version of DSF made possible using them “protein-adaptive DSF” (paDSF). paDSF can support new understanding of protein functions, and greater ability to modulate these functions with small molecules.