Original Article

Citation: Light: Science & Applications (2017) 6, e17029; doi:10.1038/lsa.2017.29
Published online 25 August 2017

Nanoplasmonic mid-infrared biosensor for in vitro protein secondary structure detection

Dordaneh Etezadi1, John B Warner IV2,*, Francesco S Ruggeri3,4,*, Giovanni Dietler3, Hilal A Lashuel2 and Hatice Altug1

  1. 1Bionanophotonic Systems Laboratory, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne CH-1015, Switzerland
  2. 2Laboratory of Molecular Neurobiology and Neuroproteomics, EPFL, Lausanne CH-1015, Switzerland
  3. 3Institute of Physics, Laboratory of the Physics of Living Matter, EPFL, Lausanne CH-1015, Switzerland
  4. 4Department of Chemistry, Lensfield road, University of Cambridge, Cambridge CB21EW, UK

Correspondence: H Altug, Email: hatice.altug@epfl.ch

*These authors contributed equally to this work.

Received 13 July 2016; Revised 17 February 2017; Accepted 23 February 2017
Accepted article preview online 27 February 2017



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 neurodegenerative 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.


label-free biosensing; nanoantennas; plasmonics; protein secondary structure; surface-enhanced infrared absorption spectroscopy