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Highly sensitive and reproducible surface enhanced Raman spectroscopy (SERS) requires not only a nanometer-level structural control, but also superb uniformity across the SERS substrate for practical imaging and sensing applications. However, in the past, increased reproducibility of the SERS signal was incompatible with increased SERS sensitivity. This work presents multiple silver nanocrystals inside periodically arrayed gold nanobowls (SGBs) via an electrochemical reaction at an overpotential of -3.0 V (vs. Ag/AgCl). The gaps between the silver nanocrystals serve as hot spots for SERS enhancement, and the evenly distributed gold nanobowls lead to a high device-to-device signal uniformity. The SGBs on the large sample surface exhibit an excellent SERS enhancement factor of up to 4.80 × 10 9 , with excellent signal uniformity (RSD < 8.0 ± 2.5%). Furthermore, the SGBs can detect specific microRNA (miR-34a), which plays a widely acknowledged role as biomarkers in diagnosis and treatment of diseases. Although the small size and low abundance of miR-34a in total RNA samples hinder their detection, by utilizing the advantages of SGBs in SERS sensing, reliable and direct detection of human gastric cancer cells has been successfully accomplished.

We present a simple wet chemical method to make thin film of silver nanoclusters on glass or silicon substrate. The method includes immersion of glass or silicon substrate into a saturated solution of silver nitrate in n-octanol. After 24 h, thin film of silver nanoclusters, which are micrometer-scale aggregates of silver nanoparticles with average size in the range of 80-100 nm, are formed on the substrate. The film is characterized by X-ray diffraction, scanning electron microscopy, atomic force microscopy, X-ray photoelectron spectroscopy, and UV-Vis spectroscopy. Potential use of the Ag nanoclusters as a surface-enhanced Raman scattering based sensing platform is demonstrated by measuring increased Raman signals from organic molecule adsorbed on the Ag nanoparticle clusters.

A two-tiered Ag nanoparticle containing a cavity at the center of each nanoparticle is generated by two simple steps of nano-imprinting and metal vacuum deposition. It enables sub-zeptomole detection of organic molecules and five orders of the dynamic sensing range., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)