Single-Atom Iron Doped Carbon Dots with Highly Efficient Electrochemiluminescence for Ultrasensitive Detection of MicroRNAs.

Herein, single-atom iron doped carbon dots (SA Fe-CDs) were successfully prepared as novel electrochemiluminescence (ECL) emitters with high ECL efficiency, and a biosensor was constructed to ultrasensitively detect microRNA-222 (miRNA-222). Importantly, compared with the conventional without single-atom doped CDs with low ECL efficiency, SA Fe-CDs exhibited strong ECL efficiency, in which single-atom iron as an advanced coreactant accelerator could significantly enhance the generation of reactive oxygen species (ROS) from the coreactant S2O82- for improving the ECL efficiency. Moreover, a neoteric amplification strategy combining the improved strand displacement amplification with Nt.BbvCI enzyme-induced target amplification (ISDA-EITA) could produce 4 output DNAs in every cycle, which greatly improved the amplification efficiency. Thus, a useful ECL biosensor was built with a detection limit of 16.60 aM in the range of 100 aM to 1 nM for detecting traces of miRNA-222. In addition, miRNA-222 in cancer cell lysate (MHCC-97L) was successfully detected by using the ECL biosensor. Therefore, this strategy provides highly efficient single-atom doped ECL emitters for the construction of sensitive ECL biosensing platforms in the biological field and clinical diagnosis.

Renewable Electrochemiluminescence Biosensor Based on Eu-MOGs as a Highly Efficient Emitter and a DNAzyme-Mediated Dual-drive DNA Walker as a Signal Amplifier for Ultrasensitive Detection of miRNA-222.

Herein, novel europium metal-organic gels (Eu-MOGs) with excellent cathode electrochemiluminescence (ECL) emission are first used to construct biosensors for the ultrasensitive detection of miRNA-222. Impressively, N and O elements of organic ligand 2,2':6,2″-terpyridine 4,4',4″-tricarboxylic acid (H3-tctpy) can perfectly coordinate with Eu3+ to form Eu-MOGs, which not only reduce nonradiative transition caused by the intramolecular free rotation of phenyl rings in other MOGs to enhance the ECL signal with extraordinary ECL efficiency as high as 37.2% (vs the [Ru(bpy)3]2+/S2O82- ECL system) but also reinforce ligand-to-metal charge transfer (LMCT) by the strong affinity between Eu3+ and N and O elements to greatly improve the stability of ECL signals. Besides, an improved nucleic acid cascade amplification reaction is developed to greatly raise the conversion efficiency from target miRNA-222 to a DNAzyme-mediated dual-drive DNA walker as output DNA, which can simultaneously shear the specific recognition sites from two directions. In that way, the proposed biosensor can further enhance the detection sensitivity of miRNA-222 with a linear range of 10 aM-1 nM and a detection limit (LOD) of 8.5 aM, which can also achieve an accurate response in cancer cell lysates of MHCC-97L and HeLa. Additionally, the biosensor can be self-regenerated by the folding/unfolding of related triplets with pH changes to simplify experimental operations and reduce the cost. Hence, this work proposed novel MOGs with stable and intense ECL signals for the construction of a renewable ECL biosensor, supplying a reliable detection method in biomarker analysis and disease diagnosis.

Selenium and nitrogen co-doped carbon dots with highly efficient electrochemiluminescence for ultrasensitive detection of microRNA.

In this work, selenium and nitrogen co-doped carbon dots (SeN-CDs) possessing highly efficient electrochemiluminescence (ECL) and excellent biocompatibility were synthesized as a new emitter with S2O82- as a coreactant for constructing a biosensor to detect microRNA-221 (miRNA-221) sensitively. Notably, the SeN-CDs exhibited superior ECL performance compared with the N-doped CDs, in which selenium with excellent redox activity served as a coreaction accelerator for facilitating the electroreduction of S2O82- to significantly improve ECL efficiency. Furthermore, target-induced T7 exonuclease (T7 Exo)-assisted double cycle amplification strategy could convert traces of target miRNA-221 into large amounts of output DNA to capture three-dimensional (3D) nanostructures (DTN-Au NPs-DOX-Fc) loaded with large amounts of ECL signal quencher. The constructed biosensor could realize ultrasensitive detection of miRNA-221 and has a low detection limit reaching 2.3 aM, with a successful application to detect miRNA-221 in lysate of Hela and MHCC97-L cancer cell. This work explored a novel method to strengthen the ECL performance of CDs to construct an ECL biosensing platform with sensitive detecting of biomarkers and disease diagnosis.

AgAuS Quantum Dots as a Highly Efficient Near-Infrared Electrochemiluminescence Emitter for the Ultrasensitive Detection of MicroRNA.

Herein, the novel alloyed silver gold sulfur quantum dots (AgAuS QDs) with highly efficient near-infrared (NIR) electrochemiluminescence (ECL) emission at 707 nm were successfully prepared to construct a biosensing platform for ultrasensitive detection of microRNA-222 (miRNA-222). Interestingly, AgAuS QDs revealed excellent ECL efficiency (34.91%) compared to that of Ag2S QDs (10.30%), versus the standard [Ru(bpy)3]2+/S2O82- system, which benefited from the advantages of abundant surface defects and narrow bandgaps by Au incorporation. Additionally, an improved localized catalytic hairpin self-assembly (L-CHA) system was developed to display an increased reaction speed by improving the local concentration of DNA strands, which addressed the obstacles of time-consuming traditional CHA systems. As a proof of concept, based on AgAuS QDs as an ECL emitter and improved localized CHA systems as a signal amplification strategy, a "signal on-off" ECL biosensor was developed to exhibit a superior reaction rate and excellent sensitivity with a detection limit of 10.5 aM for the target miRNA-222, which was further employed for the analysis of miRNA-222 from cancer cell (MHCC-97L) lysate. This work advances the exploration of highly efficient NIR ECL emitters to construct an ultrasensitive biosensor for the detection of biomolecules in disease diagnosis and NIR biological imaging.

Nitrogen-, Sulfur-, and Fluorine-Codoped Carbon Dots with Low Excitation Potential and High Electrochemiluminescence Efficiency for Sensitive Detection of Matrix Metalloproteinase-2.

In this study, nitrogen-, sulfur-, and fluorine-codoped carbon dots (NSF-CDs) with high electrochemiluminescence (ECL) efficiency were developed as novel emitters to fabricate an ECL biosensor for sensitive detection of matrix metalloproteinase 2 (MMP-2). Impressively, compared to previously reported CDs, NSF-CDs with narrow band gap not only decreased the excitation voltage to reduce the side reaction and the damage on biomolecules but also had hydrogen bonds to vastly enhance the ECL efficiency. Furthermore, an improved exonuclease III (Exo III)-assisted nucleic acid amplification method was established to convert trace MMP-2 into a mass of output DNA, which greatly improved the target conversion efficiency and ECL signal. Hence, the ECL biosensor has realized the sensitive detection of MMP-2 proteins from 10 fg/mL to 10 ng/mL with a limit of detection of 6.83 fg/mL and has been successfully applied in the detection of MMP-2 from Hela and MCF-7 cancer cells. This strategy offered neoteric CDs as ECL emitters for sensitive testing of biomarkers in medical research.

Zn2+-Induced Gold Cluster Aggregation Enhanced Electrochemiluminescence for Ultrasensitive Detection of MicroRNA-21.

Herein, Zn2+-induced gold cluster aggregation (Zn2+-GCA) as a high-efficiency electrochemiluminescence (ECL) emitter is first employed to construct an ECL biosensor to ultrasensitively detect microRNA-21 (miRNA-21). Impressively, Zn2+ not only can induce the aggregation of monodispersed gold clusters (Au NCs) to limit the ligand vibration of Au NCs for improving ECL emission but also can be utilized as a coreaction accelerator to catalyze the dissociation of coreactant S2O82- into sulfate radicals (SO4•-) to improve the interaction efficiency between Zn2+-GCA and S2O82-, resulting in further intense ECL emission. Compared to Au NCs stabilized by bovine serum albumin with ECL efficiency of 0.40%, Zn2+-GCA possessed high ECL efficiency of 10.54%, regarding the [Ru(bpy)3]2+/S2O82- system as a standard. Furthermore, output DNA modified with poly adenine (polyA) obtained from enzyme-free target recycling amplification can be efficiently immobilized on the surface of gold nanoparticles (Au NPs) to reduce the defect of special design, cumbersome operation, and low stability. Thus, an ultrasensitive ECL biosensor based on the Zn2+-GCA/S2O82- ECL system and enzyme-free target recycling amplification achieved ultrasensitive detection of miRNA-21 with the detection limit of 44.7 aM. This strategy presents a new idea to design highly efficient ECL emitters, which is expected to be used in the field of bioanalysis for clinical diagnosis.

Boron and Nitrogen-Codoped Carbon Dots as Highly Efficient Electrochemiluminescence Emitters for Ultrasensitive Detection of Hepatitis B Virus DNA.

In this work, boron and nitrogen-codoped carbon dots (BN-CDs) as highly efficient electrochemiluminescence (ECL) emitters with advantages of low excitation potential and high ECL efficiency were prepared to establish a novel ternary ECL system for ultrasensitive detection of HBV-DNA. Especially, both platinum nanoflowers (Pt NFs) and boron radicals (B•) from the BN-CDs could accelerate the reduction of coreactant S2O82- to abundant SO4•- simultaneously, making the BN-CDs have outstanding ECL performance. Impressively, the ECL efficiency of BN-CDs is much higher than that of nondoped CDs and single-doped CDs. In addition, by combining the novel ECL ternary system with the exonuclease III (Exo III)-induced target DNA amplification strategy, an ECL biosensor was constructed to realize the ultrasensitive detection of HBV-DNA from 100 aM to 1 nM, while the limit of detection was 18.08 aM. Therefore, a promising highly efficient ECL emitter was offered to develop a novel ECL detection method for clinical disease analysis.