Highly robust, uniform and ultra-sensitive surface-enhanced Raman scattering substrates for microRNA detection fabricated by using silver nanostructures grown in gold nanobowls.

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, 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.