RCA-HCR cascade mediated-linear multi-shear site DNA walker (LMDW) to construct an electrochemical biosensor for ultrasensitive detection of Tumor markers.

Herein, through the cascade integration of the RCA and HCR reactions, an innovative linear multi-shear site DNA walker (LMDW) with high walking efficiency was developed to fabricate an electrochemical biosensing platform for detecting microRNA-21 (miRNA-21) associated with breast cancer. Impressively, compared with conventional single-shear site DNA walkers with poor walking efficiency, the LMDW obtained from the RCA-confined HCR reaction can accommodate a considerable number of functional domains, increasing the shear efficiency to the hairpin probe with the beacon material, thereby consequently enhancing the reaction rate and sensitivity of the biosensor. Following validation, the probe acquisition time down to just 20 min, far less than traditional single-shear site DNA walkers and the detection limit was 0.

Environment-Friendly MnO Quantum Dots with Highly Efficient Electrochemiluminescence for Ultrasensitive Assay of Liver Cancer Markers.

In this work, environment-friendly MnO quantum dots (MnO QDs) with high efficiency were first proposed as electrochemiluminescence (ECL) emitters to construct a biosensor for ultrasensitive detection of microRNA-222 (miRNA-222) related to liver cancer markers. Compared with reported QDs containing heavy metal elements, MnO QDs not only exhibited remarkable ECL efficiency but also displayed the advantage of good biocompatibility, showing promising application prospects in the biosensor field. Impressively, silver nanoparticles (Ag NPs) as coreaction accelerators could promote the conversion of the coreactant SO into abundant SO to produce more MnO QDs* to significantly enhance the ECL efficiency of MnO QDs.

Entire Near-Infrared-I Electrochemiluminescence Enhancement of Gold Nanoclusters.

Herein, entire near-infrared-I (NIR-I) electrochemiluminescence (ECL) enhancement of gold nanoclusters (Au NCs) is achieved by continuously regulating the plasmon resonance absorption wavelength of gold nanorods (Au NRs) to precisely match ECL emission wavelength of Au NCs (abbreviated as Au NCs/Au NRs), which challenges the drawbacks of traditional single wavelength ECL enhancement strategy. Interestingly, within the range of 670-820 nm, the ECL intensity of Au NCs/Au NRs is 3-4 times higher than that of individual Au NCs due to the acceleration of electron-hole recombination and radiation transition rate through high energy electromagnetic field. As a proof of concept, the Au NCs/Au NRs with the ECL emission of 670 nm is employed as high-efficiency ECL emitter to achieve high-resolution ECL image and construct biosensor for realizing ultrasensitive detection of matrix metalloproteinase-2 (MMP-2) related to liver failure.

Silver doping-induced electrochemiluminescence enhancement of CdTe quantum dots combined with hairpin-fueled entropy-driven reactions strategy for ultrasensitive bioanalysis.

Herein, silver-doped cadmium telluride quantum dots (Ag-CdTe QDs) as electrochemiluminescence (ECL) emitter with intense ECL signal and hairpin-fueled entropy-driven reactions (H-EDR) as signal amplifier with high conversion efficiency and low signal leakage were exploited to construct an ECL biosensor for ultrasensitive determination of microRNA 222 (miRNA-222) related to liver cancer. Interestingly, the ECL intensity of Ag-CdTe QDs has been improved by 2.5 times compared to that of undoped CdTe QDs for improving the detection sensitivity, which attributed to the crystal shape transformation of Ag-CdTe QDs through silver doping for the reduction of band gap to change the electron-hole recombination path.

Dual-Mode Photoelectrochemical/ColoriMetric Biosensor with a Broad Linear Range for the Sensitive Detection of Enrofloxacin in Aquatic Products.

In this study, an integrated dual-mode biosensor combining photoelectrochemical (PEC) and colorimetric (CL) methods was proposed to broaden the linear detection range of enrofloxacin (ENR), thus enabling sensitive detection of ENR in aquatic products. Compared to traditional PEC/CL dual-mode biosensors that rely on the same sensitizer for both PEC and CL signals, this biosensor expanded the linear range and enhanced sensitivity by separating the sensitizer of PEC and the signal label of CL. Specifically, the PEC detection platform employed a Z-type heterojunction of iron indium sulfide (FeInS) and cadmium sulfide (CdS) to significantly improve the photoelectric conversion efficiency for the sensitivity of PEC detection.

Engineering DNA Nanodevices with Multi-site Recognition and Multi-signal Output for Accurate Intracellular LncRNA Imaging.

Dynamic DNA nanodevices, known for their high programmability and controllability, are pivotal in intracellular biomarker imaging. However, these nanodevices often suffer from inadequate detection sensitivity and specificity due to limited cellular loading capacity and low signal feedback. Herein, we engineered an integrated ulti-site rcognition and ulti-signal utput of fou-leaf clover dnamic DNA nanodevice () that enables sensitive and accurate intracellular long noncoding RNA (lncRNA) imaging.

Supramolecular DNA Nanodevice Assembled via RCA and HCR Cascade Reaction on Tetrahedral DNA Nanostructure for Sensitive Detection and Intracellular Imaging of Dual-miRNAs Associated with Liver Cancer.

Herein, a supramolecular DNA nanodevice was formed via the rolling circle amplification (RCA) and hybridization chain reaction (HCR) cascade reaction on a tetrahedral DNA nanostructure (TDN) to achieve simultaneous sensitive detection and intracellular imaging of dual-miRNAs related to liver cancer. The supramolecular DNA nanodevice effectively addressed the limitations of low probe loading capacity in traditional TDN nanodevices by enriching plenty of signal probes around a single TDN, significantly enhancing the fluorescence signal. Impressively, the supramolecular DNA nanodevice with a TDN fulcrum and dense DNA structure imparted the nanodevice with strong rigidity, ensuring the stability of the signal probes to decrease aggregation quenching for further increasing the fluorescence response.

Advanced Ligase Chain Reaction Strategy to Generate a Circular DNA Walker for Electrochemiluminescent Detection of Single Nucleotide Polymorphism.

Single nucleotide polymorphism (SNP) primarily refers to DNA sequence polymorphism caused by variations in a single nucleotide, which is closely associated with many diseases such as genetic disorders and tumors. However, trace DNA mutants typically exist in a large pool of wild-type DNA, making it challenging to establish accurate and sensitive approaches for SNP detection. Herein, we developed an advanced ligase chain reaction (LCR) strategy to output the circular DNA walker for signal amplification, which realized accuracy and sensitive SNP detection based on the electrochemiluminescent (ECL) platform.

Protein-Induced Electrochemiluminescence Enhancement of Tetraphenylvinyl Derivatives for Ultrasensitive Bioanalysis.

Herein, the bovine serum albumin (BSA)-loaded tetrakis[4-(4'-cyanophenyl)phenyl]ethane nanoaggregates (NAs) (BSA@TBPE-(CN) NAs) as a novel electrochemiluminescence (ECL) emitter were first prepared, which exhibited superior ECL performance via the newly defined protein-induced ECL enhancement. Impressively, BSA not only restricted the intramolecular motions by its hydrophobic cavity to improve optical radiation for enhancing ECL efficiency but also promoted the electrochemical excitation of BSA@TBPE-(CN) NAs in which amino acid residues of BSA altered the surface states and narrowed the energy gap of BSA@TBPE-(CN) NAs for further boosting the ECL efficiency. Furthermore, the BSA@TBPE-(CN) NAs displayed a more dispersed state due to electrostatic repulsion caused by its considerable negative charges, which was conducive to reacting more fully with coreactants for improving ECL emission.

Sequentially Activated-Dumbbell DNA Nanodevices for Accurate Detection of Uracil-DNA Glycosylase via PER-Based Orthogonal Signal Outputs.

Accurate and reliable detection of uracil-DNA glycosylase (UDG) activity is crucial for clinical diagnosis and prognosis assessment. However, current techniques for accurately monitoring UDG activity still face significant challenges due to the single input or output signal modes. Here, we develop a sequentially activated-dumbbell DNA nanodevice (SEAD) that enables precise and reliable evaluation of UDG activity through primer exchange reactions (PER)-based orthogonal signal output.

Multienzymatic Orthogonal Activation of DNA Codec Enables Tumor-Specific Imaging of Base Excision Repair Activity.

Accurate monitoring of base excision repair (BER) activity in cancer cells is critical for advancing the comprehension of DNA repair processes, gaining insights into cancer development, and guiding treatment strategies. However, current assay techniques for assessing BER activity in cancer cells face challenges due to the heterogeneous origins and diversity of BER enzymes. In this work, we present a hihly relible riple loop-intrlocked DNA coec (GATED) that enables precise assessment of BER activity in cancer cells through signal amplification mediated by multienzyme orthogonal activation.

Ingenious dual-circle DNA walker-mediated electrochemical biosensor for rapid and ultrasensitive detection of microRNA.

In this work, an ingenious dual-circle DNA walker (DCDW) with pretty fast walking speed and high amplification efficiency was developed for rapid and ultrasensitive electrochemical detection of microRNA-221 (miRNA-221) related to liver cancer, combined with the toehold-mediated strand-displacement reactions (TSDRs). Impressively, compared with the traditional DNA walker, the DCDW with unique double-stranded interlocked DNA nanostructure not only possesses higher stability, flexibility, and anti-entanglement ability, but also enables more functional domain in a smaller area, thereby enhancing the local concentration, which can greatly improve the working efficiency. As a validation, the electrochemical biosensor realized rapid and ultrasensitive detection of miRNA-221 with a reaction time of 15 min and detection limit down to 1.

Ultrasensitive Electrochemical Biosensor with Powerful Triple Cascade Signal Amplification for Detection of MicroRNA.

In this work, by ingeniously integrating catalytic hairpin assembly (CHA), double-end Mg-dependent DNAzyme, and hybridization chain reaction (HCR) as a triple cascade signal amplifier, an efficient concatenated CHA-DNAzyme-HCR (CDH) system was constructed to develop an ultrasensitive electrochemical biosensor with a low-background signal for the detection of microRNA-221 (miRNA-221). In the presence of the target miRNA-221, the CHA cycle was initiated by reacting with hairpins H1 and H2 to form DNAzyme structure H1-H2, which catalyzed the cleavage of the substrate hairpin H0 to release two output DNAs (output 1 and output 2). Subsequently, the double-loop hairpin H fixed on the electrode plate was opened by the output DNAs, to trigger the HCR with the assistance of hairpins Ha and Hb.

Confinement-enhanced electrochemiluminescence of copper nanoclusters on 3D layered double hydroxide for ultrasensitive detection of GFAP.

In this work, the copper nanoclusters (Cu NCs) were confined on 3D layered double hydroxide (3D-LDH) to form Cu NCs@3D-LDH with outstanding electrochemiluminescence (ECL) for constructing ultrasensitive biosensor to detect of glial fibrillary acidic protein (GFAP) implicated in Alzheimer's Disease (AD). More importantly, compared to the individual Cu NCs, Cu NCs@3D-LDH presented strong and stable ECL response, since 3D-LDH could not only gather more Cu NCs but also limit the intramolecular free motion to reduce nonradiative transition for obtaining high ECL intensity. In addition, the improved cascade amplification method combining proximity ligation assay (PLA) with DNAzyme could transform tiny amount of target protein into a large amount of output DNA to improve sensitivity of biosensor.

Nanoconfined Silver Nanoclusters Combined with X-Shaped DNA Recognizer-Triggered Cascade Amplification for Electrochemiluminescence Detection of APE1.

Apurinic/apyrimidinic endonuclease 1 (APE1), as a vital base excision repair enzyme, is essential for maintaining genomic integrity and stability, and its abnormal expression is closely associated with malignant tumors. Herein, we constructed an electrochemiluminescence (ECL) biosensor for detecting APE1 activity by combining nanoconfined ECL silver nanoclusters (Ag NCs) with X-shaped DNA recognizer-triggered cascade amplification. Specifically, the Ag NCs were prepared and confined in the glutaraldehyde-cross-linked chitosan hydrogel network using the one-pot method, resulting in a strong ECL response and exceptional stability in comparison with discrete Ag NCs.

Dual-Ligand Europium-Organic Gels as a Highly Efficient Anodic Annihilation Electrochemiluminescence Emitter for Ultrasensitive Detection of MicroRNA.

In this study, a novel europium dual-ligand metal-organic gel (Eu-D-MOGs) with high-efficient anodic annihilation electrochemiluminescence (ECL) was synthesized as an ECL emitter to construct a biosensor for ultrasensitive detection of microRNA-221 (miR-221). Impressively, compared to the ECL signal of europium single-ligand metal-organic gels (Eu-S-MOGs), the ECL signal of Eu-D-MOGs was significantly improved since the two organic ligands could jointly replace the HO and coordinate with Eu, which could remarkably reduce the nonradiative vibrational energy transfer caused by the coordination between HO and Eu with a high coordination demand. In addition, Eu-D-MOGs could be electrochemically oxidized to Eu-D-MOGs at 1.

Polymerized carbon dots with high electrochemiluminescence efficiency and long wavelength ECL emission for ultrasensitive detection of MicroRNA-222.

Herein, a new electrochemiluminescence (ECL) biosensor was constructed with highly efficient polymerized carbon dots (PCDs) as ECL emitter and the improved localized catalytic hairpin assembly (L-CHA) as signal amplifier for ultrasensitive detection of microRNA-222 (miRNA-222). Impressively, compared to the traditional carbon dots with inefficient blue region ECL emission, PCDs with N, O co-dope and large conjugated π-system showed high electrical conductivity, narrow band gap and strong radiative transition, which could exhibit high ECL efficiency to improve the sensitivity of detection and long wavelength ECL emission to achieve deep tissue penetration for reducing biological damage. Furthermore, the trace target miRNA-222 could be efficiently converted into large amounts of output DNA labelled with the quencher dopamine (S-DA) through the L-CHA reaction to significantly enhance the target amplification efficiency for further improving the sensitivity of detection.

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 Eu 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)]/SO ECL system) but also reinforce ligand-to-metal charge transfer (LMCT) by the strong affinity between Eu and N and O elements to greatly improve the stability of ECL signals.

Dynamic surface reconstruction of individual gold nanoclusters by using a co-reactant enables color-tunable electrochemiluminescence.

Here we report for the first time the phenomenon of continuously color-tunable electrochemiluminescence (ECL) from individual gold nanoclusters (Au NCs) confined in a porous hydrogel matrix by adjusting the concentration of the co-reactant. Specifically, the hydrogel-confined Au NCs exhibit strong dual-color ECL in an aqueous solution with triethylamine (TEA) as a co-reactant, with a record-breaking quantum yield of 95%. Unlike previously reported Au NCs, the ECL origin of the hydrogel-confined Au NCs is related to both the Au(0) kernel and the Au(i)-S surface.

Antibody-Protein-Aptamer Electrochemical Biosensor based on Highly Efficient Proximity-Induced DNA Hybridization on Tetrahedral DNA Nanostructure for Sensitive Detection of Insulin-like Growth Factor-1.

Herein, an antibody-protein-aptamer electrochemical biosensor was designed by highly efficient proximity-induced DNA hybridization on a tetrahedral DNA nanostructure (TDN) for ultrasensitive detection of human insulin-like growth factor-1 (IGF-1). Impressively, the IGF-1 antibody immobilized on the top vertex of the TDN could effectively capture the target protein with less steric effect, and the ferrocene-labeled signal probe (SP) bound on the bottom vertex of the TDN was close to the electrode surface for generating a strong initial signal. In the presence of target protein IGF-1 and an aptamer strand, an antibody-protein-aptamer sandwich could be formed on the top vertex of TDN, which would trigger proximity-induced DNA hybridization to release the SP on the bottom vertex of TDN; therefore, the signal response would decrease dramatically, enhancing the sensitivity of the biosensor.

Long-Wavelength Illumination-Induced Photocurrent Enhancement of a ZnPc Photocathodic Material for Bioanalytical Applications.

Herein, a novel photocathodic nanocomposite poly{4,8-bis[5-(2-ethylhexyl)-thiophen-2-yl] benzo[1,2-:4,5-']dithiophene-2,6-diyl--3-fluoro-2-[(2-ethylhexyl)-carbonyl]thieno[3,4-]thiophene-4,6-diyl}/phthalocyanine zinc (PTB7-Th/ZnPc) with high photoelectric conversion efficiency under long-wavelength illumination was prepared to construct an ultrasensitive biosensor for the detection of microRNA-21 (miRNA-21), accompanied by a prominent anti-interference capability toward reductive substances. Impressively, the new heterojunction PTB7-Th/ZnPc nanocomposite could not only generate a strong cathodic photocurrent to improve the detection sensitivity under long-wavelength illumination (660 nm) but also effectively avoid the high damage of biological activity caused by short-wavelength light stimulation. Accordingly, by coupling with rolling circle amplification (RCA)-triggered DNA amplification to form functional biquencher nanospheres, a PEC biosensor was fabricated to realize the ultrasensitive analysis of miRNA-21 in the concentration range of 0.

Near-Infrared-Driven Nanorocket for Rapid and Ultrasensitive Detection of MicroRNA.

Herein, by introducing gold nanostars (AuNSs) as fuel core, a near-infrared-driven nanorocket (NIDNR) with pretty fast walking was exploited for ultrasensitive miRNA detection. Compared with traditional nanomaterials-comprised nanomachines (NMs), the NIDNR possesses much better kinetic and thermodynamic performance owing to the extra photothermal driving force from localized surface plasmon (LSP). Impressively, the whole reaction time of NIDNR down to 15 min was realized, which is almost more than 8 times beyond those of conventional DNA-based NMs.

pH-Stimulated Self-Locked DNA Nanostructure for the Effective Discrimination of Cancer Cells and Simultaneous Detection and Imaging of Endogenous Dual-MicroRNAs.

In this study, a pH-stimulated self-locked DNA nanostructure (SLDN) was developed to efficiently distinguish cancer cells from other cells for the simultaneous detection and imaging of endogenous dual-microRNAs (miRNAs). Impressively, the SLDN was specifically unlocked in the acidic environment of cancer cells to form unlocked-SLDN to disengage the i-motif sequence with a labeled fluorophore for the recovery of a fluorescence signal, resulting in the differentiation of cancer cells from normal cells. Meanwhile, unlocked-SLDN could combine and recognize the targets miRNA-21 and miRNA-155 simultaneously to trigger the hybridization chain reaction (HCR) amplification for sensitive dual-miRNA detection, with detection limits of 1.

Gold Nanobipyramid Hotspot Aggregation-Induced Surface-Enhanced Raman Scattering for the Ultrasensitive Detection of miRNA.

Herein, a surface-enhanced Raman scattering (SERS) biosensor was constructed by gold nanobipyramid (Au NBP) hotspot aggregation-induced SERS (HAI-SERS) for the ultrasensitive detection of microRNA-221 (miRNA-221). Impressively, compared with single Au NBP, the multiple Au NBPs assembled by tetrahedral DNA nanostructures (TDNs) could increase hotspot aggregation to significantly enhance the SERS signal of Raman molecule methylene blue (MB). Meanwhile, in the aid of Exo-III assisted target cycle amplification and TDNs-induced catalytic hairpin assembly (CHA) amplification, the biosensor could achieve the sensitive detection of miRNA-221 with a linear range of 1 fM-10 nM, and the limit of detection (LOD) was 0.