Ultrafast Laser-Induced 1T′/2H-MoTe₂ Nanopattern with Au-Nanoclusters for Raman Monitoring of Cellular Drug Metabolism

The development of surface-enhanced Raman spectroscopy (SERS) as an ultrasensitive fingerprint analysis technique in precision medicine requires high-performance SERS substrates with controllable nanostructure (hot-spot) distribution, simple fabrication, superior stability, biocompatibility, and extraordinary optical responses. Unfortunately, fabrication of arbitrary nanostructures with high homogeneity on a large scale for SERS is still challenging. Herein, we report an ultrafast laser parallel fabrication protocol for Au/2D-transition-metal dichalcogenide hybrid SERS biosensors. The leveraged photonic nanojets (PNJs) are generated by a micron-sized microsphere monolayer to simultaneously trigger localized phase transition in 2H-MoTe 2, achieving a 1T′-MoTe 2 nanopattern array with a density of 1 million per mm 2 by a single laser shot. The Au nanoparticle clusters (AuNCs) are subsequently grown in situ from the 1T′ regions, creating a AuNCs on 1T′/2H-MoTe 2 (AuNCs@1T’/2H-MoTe 2 ) hybrid SERS substrate. The fabricated feature diameter and overlay accuracy of the patterned AuNCs are 210.1 ± 3.4 and 9.2 ± 1.7 nm, respectively. To eliminate background noise, we designed dimer-AuNCs@1T′/2H-MoTe 2 (dAuNCs@1T′/2H-MoTe 2 ), achieving a detection limit of 10 –13 M with an enhancement factor of 4.9 × 10 8 for the methylene blue (MB) analyte. The strong localized surface plasmon resonances in the dAuNCs as well as efficient charge transfers between Au, 2H-MoTe 2, and MB contribute to the majority of Raman enhancement. The multiscale dAuNCs@1T′/2H-MoTe 2 array provides a powerful SERSome (comprising multiple SERS spectra) platform for therapeutic drug monitoring, by which we successfully identified the metabolic behaviors of living gastric adenocarcinoma cells administered with two drugs, i.e., capecitabine, oxaliplatin, and their combination. The present work establishes opportunities for creating a highly ordered nanopattern array for ultrasensitive SERSome analysis of cell metabolism in cancer therapy.