Topology-controlled plasmonic nanocapsules enable more sensitive quantitative SERS detection of zinc

Quantifying labile Zn(II) in complex biological media remains challenging for optical nanosensors because matrix effects and SERS substrate heterogeneity distort signal intensities. We report here topology-controlled plasmonic Au@SiO 2 nanocapsules functionalized with a thiolated terpyridine (TPY) Raman reporter as ratiometric SERS nanosensors for quantitative zinc detection. The denser apparent AuNP loading and red-shifted/broadened UV–Vis-NIR response are consistent with stronger interparticle plasmon coupling and improved overlap with 785 nm excitation. Labile zinc binding is quantified using an integrated-band ratio in the 1000–1050 cm -1 region, enabling robust calibration in a zinc-depleted cell-culture-derived matrix used as a controlled biologically relevant calibration medium. The optimized formulation shows improved linearity (R 2 up to 0.99) over 10 –4 – 10 –12 M Zn(II) and a condition-specific statistical LOD of 1.7 × 10 –13 M (10 –12.77 M), outperforming our earlier formulation. Density functional theory calculations support vibrational assignment of Zn-TPY marker bands and guide future selection for quantification. These results establish nanocapsule topology as an effective tuning parameter for improving quantitative Zn(II) readouts under controlled cell-culture-medium conditions.