Yao Yao, Zhao Yue, Zhang Huijuan, Pan Wenting, Liang Wei, Jiang Yijian, Yan Xinlong, Yan Yinzhou
School of Physics and Optoelectronic Engineering, Beijing University of Technology, Beijing 100124, China.
Beijing International Science and Technology Cooperation Base for Antiviral Drugs, Beijing Key Laboratory of Environmental and Viral Oncology, College of Chemistry and Life Science, Beijing University of Technology, Beijing 100124, China.
ACS Nano. 2025 May 6;19(17):16732-16743. doi: 10.1021/acsnano.5c01351. Epub 2025 Apr 17.
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, achieving a 1T'-MoTe nanopattern array with a density of 1 million per mm 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 (AuNCs@1T'/2H-MoTe) 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 (dAuNCs@1T'/2H-MoTe), achieving a detection limit of 10 M with an enhancement factor of 4.9 × 10 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, and MB contribute to the majority of Raman enhancement. The multiscale dAuNCs@1T'/2H-MoTe 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.
表面增强拉曼光谱（SERS）作为精准医学中的一种超灵敏指纹分析技术，其发展需要具备可控纳米结构（热点）分布、制备简单、稳定性优异、生物相容性良好以及非凡光学响应的高性能SERS基底。不幸的是，大规模制备具有高均匀性的任意纳米结构用于SERS仍然具有挑战性。在此，我们报道了一种用于金/二维过渡金属二卤化物混合SERS生物传感器的超快激光并行制备方案。利用由微米级微球单层产生的光子纳米射流（PNJs）同时触发2H-MoTe中的局部相变，通过单次激光照射实现每毫米密度为100万个的1T'-MoTe纳米图案阵列。随后，金纳米颗粒簇（AuNCs）在1T'区域原位生长，从而创建了一种1T'/2H-MoTe上的AuNCs（AuNCs@1T'/2H-MoTe）混合SERS基底。所制备的图案化AuNCs的特征直径和覆盖精度分别为210.1±3.4和9.2±1.7纳米。为了消除背景噪声，我们设计了二聚体-AuNCs@1T'/2H-MoTe（dAuNCs@1T'/2H-MoTe），对于亚甲基蓝（MB）分析物实现了10⁻¹¹ M的检测限和4.9×10⁶的增强因子。dAuNCs中强烈的局部表面等离子体共振以及金、2H-MoTe和MB之间的有效电荷转移对大部分拉曼增强起作用。多尺度dAuNCs@1T'/2H-MoTe阵列提供了一个强大的SERSome（包含多个SERS光谱）平台用于治疗药物监测，通过该平台我们成功识别了给予两种药物（即卡培他滨、奥沙利铂及其组合）的活胃腺癌细胞的代谢行为。本工作为创建用于癌症治疗中细胞代谢超灵敏SERSome分析的高度有序纳米图案阵列创造了机会。
