Chiral plasmonic nanostructures have emerged as powerful probes of chirality, yet most rely solely on passive optical asymmetry and rarely exploit analyte manipulation strategies. This limitation constrains their sensitivity and generality across diverse molecular systems. Integrating chirality across multiple length scales offers new design rules for enantiospecific recognition. Herein, we report chiral gold nanoflowers (Au NFs) with three-dimensional helical petals that embed chirality hierarchically at the nano-, atomic, and molecular scales to couple electromagnetic enhancement with active analyte manipulation. The three-level chirality-driven recognition mechanism involves nanoscale chiral near-fields, atomic-level facet asymmetry that drives enantiospecific physisorption, and residual cysteine-mediated chemisorption. Despite a modest g-factor (2.4 × 10-3), these Au NFs achieve an analytical enhancement factor exceeding 108, enabling 100% accurate surface-enhanced Raman scattering (SERS) discrimination of pharmaceutical enantiomers at sub-μM concentrations and multiplex mixture analysis with >95% accuracy. By incorporating analyte manipulation strategies, this work establishes multiscale chirality as a general principle for high-precision chiral recognition applicable to sensing, chiral catalysis, and chiroptical materials.
Jia et al. (Fri,) studied this question.