Dual-Mode SERS and Electrochemical Detection of miRNA Based on Popcorn-like Gold Nanofilms and Toehold-Mediated Strand Displacement Amplification Reaction

Abstract

MicroRNA (miRNA) has emerged as one of the ideal target biomarker analytes for cancer detection because its abnormal expression is closely related to the occurrence of many cancers. In this work, we combined three-dimensional (3D) popcorn-like gold nanofilms as novel surface-enhanced Raman scattering (SERS)-electrochemistry active substrates with toehold-mediated strand displacement reactions (TSDRs) to construct a DNA molecular machine for SERS-electrochemistry dual-mode detection of miRNA. 3D popcorn-like spatial structures generated more active “hot spots” and thus enhanced the sensitivity of SERS and electrochemical signals. Besides, the TSDRs showed high sequence-dependence and high specificity. The addition of target miRNA will trigger the molecular machine to perform two TSDRs in the presence of signal DNA strands modified by R6G (R6G-DNA), thus achieving an enzyme-free amplification detection of miRNA with a low limit of detection of 0.12 fM (for the SERS method) and 2.2 fM (for the electrochemical method). This biosensor can also serve as a universally amplified and sensitive detection platform for monitoring different biomarkers, such as cancer-related DNA, messenger RNA, or miRNA molecules, with high selectivity by changing the corresponding probe sequence.

Ultrasensitive Surface‐Enhanced Raman Scattering (SERS) Detection For miRNA‐182 Based on CdS/MoS2@AuNPs Fabricated by Atomic Layer Deposition (ALD)

“…Comparing with previous work, the CdS/MoS 2 @AuNPs based SERS platform prepared in this paper has a better linear range and the lowest detection limit (Figure 5d). [ 42–50 ]…”

Electrochemistry/Photoelectrochemistry-Based Immunosensing and Aptasensing of Carcinoembryonic Antigen

“…Nucleic acid-based amplification technologies, such as strand displacement reaction (SDR) [63][64][65], metal ion-dependent DNAzyme [66,67], hybridization chain reaction (HCR) [68][69][70], and nuclease cycling cleavage [71,72] remarkably enhanced the detection sensitivity. Zhao et al designed an ultrasensitive impedimetric CEA aptasensor based on the amplification effect of Zn 2+ -dependent DNAzyme-inspired cycling cleavage [73].…”

Recent Advances in Signal Amplification to Improve Electrochemical Biosensing for Infectious Diseases

“…Recent papers have mainly focused on detection of miRNA. For example, toehold-mediated SDA was combined with surface-enhanced Ramen-scattering electrochemistry for dual-mode detection of miRNA, achieving an LOD as low as 0.12 fM ( Zhou et al, 2021 ). We cite relevant reviews on isothermal amplification for readers interested in further reading ( Monis and Giglio, 2006 ; Zhao et al, 2015 ).…”