Versatile and Ultrasensitive Electrochemiluminescence Biosensor for Biomarker Detection Based on Nonenzymatic Amplification and Aptamer-Triggered Emitter Release

Abstract

Electrochemiluminescence (ECL), as a sensitive and controllable assay, offers a considerable opportunity for multiple types of biomarkers detection. However, constructing such a biosensor remains a significant challenge. Herein, an ultrasensitive and versatile ECL biosensor was constructed to detect multiple types of biomarkers from breast cancer by taking the strategies of nonenzymatic catalytic hairpin assembly (CHA) and hybridization chain reaction (HCR) amplification, as well as aptamer-triggered emitter release. Concretely, with the appearance of target 1 microRNA-21 (miRNA-21), abundant double-stranded DNA (dsDNA) polymers were generated on this biosensing surface via amplification circuits of CHA and HCR, which could be intercalated into substantial ([Ru(bpy) 2 dppz]Cl 2 ) as ECL indicators to obtain an obvious enhancement of ECL signal for target 1 detection with a detection limit (0.1 fM). Furthermore, in the presence of target 2 human mucin 1 (MUC1) protein, the ECL signal had a distinct decrease, because aptamer recognition induced the release of [Ru(bpy) 2 dppz]Cl 2 from the sensing surface, thus, achieving a sensitive detection for MUC1 with a detection limit (2.4 fg•mL −1 ). Simultaneously, this sensing platform was applied to monitor the biomarkers from MDA-MB-231 breast cancer cells, suggesting that this method was applicable to detect real samples. Therefore, this platform is an applicable and versatile implement for the determination of multiple types of biomarkers to improve diagnostic accuracy and efficiency.

Applications of Graphene Quantum Dots in Biomedical Sensors

“…Consequently, the conversion of an excited state into the ground state (i.e., from unstable to stable) leads to the emission of light. Accordingly, the formation of the free radicals in ECL occurs, which are segregated into the co-reaction and quenching pathways [184][185][186]. ECL sensing techniques exhibit excellent features including high sensitivity, rapid speed of response and easy operational procedures.…”

Applications of Catalytic Hairpin Assembly Reaction in Biosensing

“…The rational design of sticky ends can bring branched DNA junctions into full play. In addition to the initial signal amplification, the sensing platforms based on branched DNA junctions show significantly improved sensitivity because the ends of every arm can be engineered to form DNAzymes, transduce other isothermal amplification methods, and bind with nanoparticles to further amplify signals. With additional hairpins, the process and final structure are more complicated.…”

“…Although the entity of CHA is nucleic acid strand displacement, the detection targets are not confined to nucleic acids. Many other analytes including metal ions, proteins, enzymes, and even cancer cells have been measured based on CHA.…”

Recent Progress of Biomarker Detection Sensors

“…As is shown in Figure 4(a) , Nie et al successfully designed a versatile and ultrasensitive ECL sensing platform to monitor breast cancer biomarkers by using a nonenzymatic catalytic hairpin assembly and hybridization chain reaction for amplifying [ 92 ]. Combing with nanoparticles, biomaterial-based biosensors also exhibit potential for progress.…”

“… Secondary label decoration strategies with different types of materials. (a) ECL-based biomarker sensor amplified its output by decorating biology material and NPs on the biomarker, reproduced from Nie et al [ 92 ]. (b) Combing with the GNPs, the biosensor was optimized by controlling the thickness of the shell, reproduced from Zhao et al [ 93 ] with their permissions.…”