Pathogenesis in protein conformational diseases is initiated by changes in protein secondary structure. This molecular restructuring presents an opportunity for novel shape-based detection approaches, as protein molecular weight and chemistry are otherwise unaltered. Here we apply molecular imprinting to discriminate between distinct conformations of the model protein beta-lactoglobulin (BLG). Thermal- and fluoro-alcohol-induced BLG isoforms were imprinted in thin films of 3-aminophenylboronic acid on quartz crystal microbalance chips. Enhanced rebinding of the template isoform was observed in all cases when compared to the binding of nontemplate isoforms over the concentration range of 1-100 microg mL(-1). Furthermore, it was observed that the greater the changes in the secondary structure of the template protein the lower the binding of native BLG challenges to the imprint, suggesting a strong steric influence in the recognition system. This feasibility study is a first demonstration of molecular imprints for recognition of distinct conformations of the same protein.