• Glucose and fructose induce distinct chiral-selective spectral changes in Phe SERS. • Detection limits of 10-9 M were achieved for chiral sensing of monosaccharides. • Principal component analysis provides a good quantitative measure for mixtures. • Phe SERS demonstrates potential for multimodal chiral sensing of biological targets. The chirality of biomolecules plays a crucial role in biological processes. Recently, surface-enhanced Raman scattering (SERS)-based chiral sensing studies have been reported. However, a comprehensive understanding of the enantioselective interactions between analytes and reporters/nanostructures and the resultant SERS spectral changes has often been overlooked. Herein, we report SERS-based chiral sensing of monosaccharides fructose (Fru) and glucose (Glc), using a reporter, L- and D-phenylalanine (Phe) on gold nanoparticles (AuNPs). Phe SERS spectra provide molecule-level information on the surface adsorption of Phe on AuNPs, and exhibit analyte-specific changes upon addition of chirally matching monosaccharides. One-to-one bimolecular chiral interactions between Glc/Fru and Phe provide distinct spectral evidence for monosaccharide identity and quantitative information on analyte concentrations, enabling extension of the chiral sensing by Phe SERS to other monosaccharide epimers. Multimodal chiral sensing of Glc/Fru mixtures, implemented by principal component analysis (PCA), yielded two distinct principal component (PC) loadings, PC1 and PC2, similar to the Phe SERS obtained exclusively with Fru and Glc, respectively. The PC1 and PC2 scores of individual spectra show strong linear correlations with the Fru or Glc mole fraction in mixtures, enabling multimodal chiral sensing with highly specific monosaccharide identification. This work demonstrates the potential of Phe SERS on AuNPs to be further developed into a novel multimodal chiral sensing strategy for a wide range of chiral biological targets.
Lee et al. (Sun,) studied this question.