Metamaterials-Based Label-Free Nanosensor for Conformation and Affinity Biosensing

Analysis of molecular interaction and conformational dynamics of biomolecules is of paramount importance in understanding their vital functions in complex biological systems, disease detection, and new drug development. Plasmonic biosensors based upon surface plasmon resonance and localized surface plasmon resonance have become the predominant workhorse for detecting accumulated biomass caused by molecular binding events. However, unlike surface-enhanced Raman spectroscopy (SERS), the plasmonic biosensors indeed are not suitable tools to interrogate vibrational signatures of conformational transitions required for biomolecules to interact. Here, we show that highly tunable plasmonic metamaterials can offer two transducing channels for parallel acquisition of optical transmission and sensitive SERS spectra at the biointerface, simultaneously probing the conformational states and binding affinity of biomolecules, e.g., G-quadruplexes, in different environments. We further demonstrate the use of the metamaterials for fingerprinting and detection of the arginine-glycine-glycine domain of nucleolin, a cancer biomarker that specifically binds to a G-quadruplex, with the picomolar sensitivity.