Gold Nanoparticle-Decorated Ag@SiO2 Nanocomposite-Based Plasmonic Affinity Sandwich Assay of Circulating MicroRNAs in Human Serum

Circulating microRNAs (miRNAs) hold great value in the diagnostics of cancer diseases. Ultrasensitive detection schemes are essential for the determination of circulating miRNAs, due to the limited levels of miRNAs in human serum. To this end, surface enhanced Raman scattering (SERS), which relies on plasmonic nanomaterials to amplify the Raman signal, has evolved as a promising tool. However, plasmonic nanomaterials that allow for fast and ultrasensitive SERS detection are still much needed. Herein, we proposed a fast and ultrasensitive strategy for the determination of circulating miRNAs in human serum, called gold nanoparticle (AuNP)-decorated Ag@SiO2 nanocomposite-based plasmonic affinity sandwich assay (PASA). We first theoretically verified the presence of multiple hot-spots around the nanocomposite and then experimentally demonstrated the improved detection sensitivity generated by the AuNP-decorated Ag@SiO2 nanocomposite. The PASA approach exhibited several significant advantages including ultrahigh sensitivity (the limit of quantification was 10 fM), fast speed (the total analysis time was only 3 h), and very low sample volume requirement (only 5 μL). Quantification of miR-21 in human serum was achieved by the method, which allowed for differentiation of a breast cancer patient from a healthy individual. The AuNP-decorated Ag@SiO2 nanocomposite and the PASA method can be easily extended for other microRNAs and circulating tumor DNA. Therefore, the PASA method holds great promise for cancer diagnosis.