Attomole enantiomeric discrimination of small molecules using an achiral SERS reporter and chiral plasmonics

Biologically important molecules span a size range from very large biomacromolecules, such as proteins to small metabolite molecules. Consequently, spectroscopic techniques which can detect and characterize the structure of inherently chiral biomolecules over this range of scale at the femtomole level are necessary to develop novel biosensing and diagnostic technologies. Nanophotonic platforms uniquely enable chirally sensitive structural characterisation of biomacromolecules at this ultrasensitive level. However, they are less successful at achieving the same level of sensitivity for small chiral molecules, with less than nanomole typical. This poorer performance can be attributed to the optical response of the platform being sensitive to a much larger volume of the near field than is occupied by the small molecule. Here we show that by combining chiral plasmonic metasurfaces with Raman reporters, which can detect changes in electromagnetic environment at molecular dimensions, chiral discrimination can be achieved for attomole quantities of a small molecule, the amino acid cysteine. The signal-to-noise, and hence ultimate sensitivity, of the measurement can be further improved by combining the metasurfaces with gold achiral nanoparticles. This indirect enantiomeric detection is 9 orders of magnitude more sensitive than strategies relying on monitoring the Raman response of target chiral molecules directly. Given the generic nature of the phenomenon,this study provides a framework for developing novel technologies for detecting a broad spectrum of small biomolecules, which would be useful tools in the field of metabolomics

Chiral Metafilms and Surface Enhanced Raman Scattering For Enantiomeric Discrimination of Helicoid Nanoparticles

Chiral nanophotonic platforms provide a means of creating near fields with both enhanced asymmetric properties and intensities. They can be exploited for optical measurements that allow enantiomeric discrimination at detection levels greater than 6 orders of magnitude than is achieved with conventional chirally sensitive spectroscopic methods based on circularly polarized light. The optimal approach for exploiting nanophotonic platforms for chiral detection would be to use spectroscopic methods that provide a local probe of changes in the near field environment induced by the presence of chiral species. Here we show that surface enhanced Raman spectroscopy (SERS) is such a local probe of the near field environment. We have used it to achieve enantiomeric discrimination of chiral helicoid nanoparticles deposited on left and right-handed enantiomorphs of a chiral metafilm. Hotter electromagnetic hotspots are created for matched combinations of helicoid and metafilms (left-left and right-right), while mismatched combinations leads to significantly cooler electromagnetic hotspots. This large enantiomeric dependency on hotspot intensity is readily detected using SERS with the aid of an achiral Raman reporter molecule. In effect we have used SERS to distinguish between the different EM environments of the plasmonic diastereomers produced by mixing chiral nanoparticles and metafilms. The work demonstrates that by combining chiral nanophotonic platforms with established SERS strategies new avenues in ultrasensitive chiral detection can be opened

Near-field probing of optical superchirality with plasmonic circularly polarized luminescence for enhanced bio-detection

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

Ultrasensitive Raman detection of biomolecular conformation at the attomole scale using chiral nanophotonics

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