Botulinum neurotoxins (BoNT) are the etiological agents responsible for botulism and are acknowledged terrorist threat agents. Passive immunotherapy may provide one countermeasure. Importantly, in the virtually unlimited repertoire of antibody specificities, enzyme linked immunosorbent assays (ELISA) has become an indispensable method for antibody selection. We report that of the BoNTs, BoNT/E is highly susceptible to polystyrene induced denaturation. To further dissect this result and the potential susceptibility of other BoNTs to denaturation we selected a thermal platform, which could be readily quantified using surface plasmon resonance (SPR), a primary rat spinal cord cell-based assay and an animal lethality model.