ABSTRACT
Understanding the function of a biomolecule hinges on its 3D conformation or secondary structure. Chirally sensitive, optically active techniques based on the differential absorption of UV-vis circularly polarized light excel at rapid characterisation of secondary structures. However, Raman spectroscopy, a powerful method for determining the structure of simple molecules, has limited capacity for structural analysis of biomolecules because of intrinsically weak optical activity, necessitating millimolar (mM) sample quantities. A breakthrough is presented for utilising Raman spectroscopy in ultrasensitive biomolecular conformation detection, surpassing conventional Raman optical activity by 15 orders of magnitude. This strategy combines chiral plasmonic metasurfaces with achiral molecular Raman reporters and enables the detection of different conformations (α-helix and random coil) of a model peptide (poly-L/D-lysine) at the ≤attomole level (monolayer). This exceptional sensitivity stems from the ability to detect local, molecular-scale changes in the electromagnetic (EM) environment of a chiral nanocavity induced by the presence of biomolecules using molecular Raman reporters. Further signal enhancement is achieved by incorporating achiral Au nanoparticles. The introduction of the nanoparticles creates highly localized regions of extreme optical chirality. This approach, which exploits Raman, a generic phenomenon, paves the way for next-generation technologies for the ultrasensitive detection of diverse biomolecular structures.
ABSTRACT
Nanophotonic platforms in theory uniquely enable < femtomoles of chiral biological and pharmaceutical molecules to be detected, through the highly localized changes in the chiral asymmetries of the near fields that they induce. However, current chiral nanophotonic based strategies are intrinsically limited because they rely on far field optical measurements that are sensitive to a much larger near field volume, than that influenced by the chiral molecules. Consequently, they depend on detecting small changes in far field optical response restricting detection sensitivities. Here, we exploit an intriguing phenomenon, plasmonic circularly polarized luminescence (PCPL), which is an incisive local probe of near field chirality. This allows the chiral detection of monolayer quantities of a de novo designed peptide, which is not achieved with a far field response. Our work demonstrates that by leveraging the capabilities of nanophotonic platforms with the near field sensitivity of PCPL, optimal biomolecular detection performance can be achieved, opening new avenues for nanometrology.
