How Does a 2D Chiral Superlattice Enable Label-Free SERS for Precise Chiral Molecule Detection?

It works because the TaS₂ layers were modified to create a chiral superlattice. By inserting chiral α-methylbenzylamine, the layer spacing doubled, forming a strong chiral environment. This makes it possible to tell tiny differences between enantiomers without any labels. The system can detect D- and L-glucose at sub-nanomolar levels and even works in real saliva with almost zero error. It’s stable for months and also works for amino acids like histidine, which means it could help spot early cancer markers. In the future, it might be built into tiny sensors for drug quality checks and disease diagnosis.

The uniqueness of the 2D chiral superlattice of TaS₂ lies in its structure and properties formed by inserting chiral α-methylbenzylamine into TaS₂ layers. The interlayer spacing expands from 6.0 Å to 12.2 Å, creating S/R-TaS₂ superlattices with mirror circular dichroism responses. This structure enables strong interactions with chiral molecules like D-/L-glucose, enhancing Raman signals specifically. Such high sensitivity (sub-nanomolar detection of glucose) stems from the superlattice's tailored chiral environment that matches molecular chirality, amplifying fingerprint SERS signals without labels.

This method is applicable to other biomolecules. It works for D-/L-histidine with a 1.5 nM detection limit, and can potentially detect early cancer markers by targeting their chiral features. In real-world applications, its stability (signal unchanged after 2-month storage) and accuracy (＜1% error in saliva) suit drug quality control (enantiomer purity checks) and clinical diagnostics (e.g., glucose in saliva).

Compared to traditional methods, it avoids external chiral selectors, simplifying operations. Unlike low-sensitivity traditional optics, it achieves ultra-high sensitivity. A potential misunderstanding is assuming it’s limited to glucose, but its universality allows broader biomolecule detection.

This two-dimensional chiral superlattice constructed from TaS₂ achieves label-free SERS detection with exceptional sensitivity due to its unique structural and optical properties. The insertion of chiral α-methylbenzylamine (MBA) molecules between TaS₂ layers expands the interlayer spacing and creates a chiral environment with pronounced circular dichroism. This architecture provides a high density of “hot spots” for surface-enhanced Raman scattering (SERS), significantly amplifying the Raman signals of chiral molecules adsorbed on the surface. More importantly, the intrinsic chirality of the superlattice enables selective interaction with specific molecular enantiomers, leading to distinct SERS fingerprints for D- and L-forms without requiring external labeling agents.

The system exhibits sub-nanomolar detection limits for glucose due to strong chiral plasmonic coupling and enhanced local electromagnetic fields, allowing direct identification and quantification of enantiomers. This mechanism is broadly applicable to other biomolecules such as amino acids (e.g., histidine was detected at 1.5 nM) and potentially to early cancer markers involving chiral biomarkers.

Real-world applications include drug quality control—ensuring enantiomeric purity of pharmaceuticals—and clinical diagnostics, such as continuous glucose monitoring in saliva with high accuracy and long-term stability. The platform can be integrated into portable chip-based sensors, offering a versatile tool for metabolic tracking and early disease diagnosis.