Dual-signal SERS biosensor based on spindle-shaped gold array for sensitive and accurate detection of miRNA 21

MicroRNAs (miRNAs) play an important regulatory role in tumor progression and have been emerging as promising biomarkers for early diagnosis of breast cancer. Herein, we developed a dual-signal surface-enhanced Raman scattering (SERS) biosensor for the quantitative detection of miRNA 21 (miR-21) by utilizing a tightly ordered spindle-shaped gold (SAu) array with 5, 5’-dithio-bis-(2-nitrobenzoic acid) (DTNB) molecule as an internal standard. Meanwhile, 6-carboxyl-Xrhodamine (ROX) labeled hairpin DNA H1 was linked to the SAu array by Au–S bonds generating another SERS signal. In the presence of miR-21, H1 was turned on with a decrease in SERS signal of ROX, while the SERS signal of DTNB remained stable. The SAu array as substrate provides a large area of hot spots, and the dual-signal can avoid background interference and achieve signal self-calibration. By the dual-signal SERS biosensor, target miR-21 could be detected over a broad linear range (0.1−105 pM) with a low detection limit (0.046 pM) without signal amplification strategy. Thanks to the SAu array and dual-signal output, the sensor showed high sensitivity, good signal reproducibility, excellent specificity, and high detection accuracy. When this sensor was applied to the miR-21 assay in human serum samples, its performance was comparable to quantitative reverse transcription polymerase chain reaction (qRT-PCR), indicating promising applications of the developed sensor for cancer diagnostics.