Plasmonic nanoantennas offer new applications in mid-infrared (mid-IR) absorption spectroscopy with ultrasensitive detection of structural signatures of biomolecules,such as proteins,due to their strong resonant near-fields.The amide I fingerprint of a protein contains conformational information that is greatly important for understanding its function in health and disease.Here,we introduce a non-invasive,label-free mid-IR nanoantenna-array sensor for secondary structure identification of nanometer-thin protein layers in aqueous solution by resolving the content of plasmonically enhanced amide I signatures.We successfully detect random coil to cross β-sheet conformational changes associated with α-synuclein protein aggregation,a detrimental process in many neumdegenerative disorders.Notably,our experimental results demonstrate high conformational sensitivity by differentiating subtle secondary-structural variations in a native β-sheet protein monolayer from those of cross β-sheets,which are characteristic of pathological aggregates.Our nanoplasmonic biosensor is a highly promising and versatile tool for in vitro structural analysis of thin protein layers.