Uniform 3D SERS substrate SiO2@AuAg collaborate with target-mediated DNA network structure as a signal amplifier for ultrasensitive detection of miRNA-21

Abstract

The uniformity of the SERS substrate significantly affects the signal reproducibility and sensitivity of the sensor. Therefore, optimizing uniformity of the substrate is crucial for enhancing the overall performance of SERS sensors. Herein, a uniform SERS substrate SiO₂@AuAg, combined with a target-mediated DNA network structure as a signal amplifier, was developed to construct a three-dimensional (3D) SERS sensor for the ultrasensitive detection of miRNA-21. Specifically, the highly uniform 3D SERS substrate SiO₂@AuAg is fabricated through liquid-liquid self-assembly. The orderly 3D structure provides a significantly larger specific surface area and an increased number of “hot spots”, thereby enhancing both the sensitivity and the repeatability of the proposed method. Additionally, DNA nanoflowers (DNFs) formed through self-assembly can incorporate a large number of methylene blue (MB) molecules, creating a stable 3D network structure on the SiO₂@AuAg surface upon hybridization chain reaction induced by target miRNA-21. With the establishment of this 3D detection structure, the biosensor achieves ultrasensitive detection of miRNA-21 through a “signal-on” strategy, with a detection limit as low as 2.65 × 10⁻¹⁵ mol/L. Furthermore, this strategy offers a novel approach for designing advanced SERS biosensors for rapid and sensitive miRNA detection.