An efficient signal amplification strategy with low background based on a G-quadruplex-enriched DNA nanonetwork for ultrasensitive electrochemical detection of mucin 1.

Herein, a G-quadruplex-enriched DNA nanonetwork (GDN) self-assembled via Y-modules was designed to construct an ultrasensitive electrochemical biosensing platform with low background for the detection of mucin 1 related to cancers. The single-stranded DNA (ssDNA) S1 converted from target mucin 1 could hybridize with ssDNA S2 and ssDNA S3 with split G-quadruplex fragments at ends to form Y-modules and self-assemble into a GDN, which can capture abundant electroactive substance hemin for a significant electrochemical signal. Impressively, compared with conventional G-quadruplex nanowires with low loading capacity and poor structural stability, the GDN assembled by Y-modules was able to load more signaling probes and obtain a more stable structure for the support of G-quadruplexes, thereby outputting a stronger and more stable electrochemical signal.

Spatial Confinement-Enhanced Electrochemiluminescence of Gold Nanoclusters on 3D Porous ZrO Hollow Nanospheres for the Assessment of Acute Myocardial Infarction Protein Markers.

Herein, the gold nanoclusters@three-dimensional (3D) porous ZrO hollow nanospheres (Au NCs@ZrO) with spatial confinement-enhanced electrochemiluminescence (SCE-ECL) were first prepared to fabricate a biosensing platform for the ultrasensitive detection of insulin-like growth factor 1 (IGF-1), which was associated with cardiovascular disease, malignant tumor, and neuropathic pain. Specifically, the confinement of Au NCs in a 3D microenvironment significantly boosted the optical radiation of excited Au NCs because the vibration of ligand molecules was restricted, and the recombination of holes and electrons of excited Au NCs was facilitated in the optical process for enhancing ECL efficiency, resulting in 5.1-fold stronger ECL efficiency than Au NCs.

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.

Surface Charge Redistribution-Induced Electrochemiluminescence Enhancement of Gold Nanoclusters: The Novel Generation of Efficient Illuminants.

Herein, we developed the agmatine/6-aza-2-thiothymine templated gold nanoclusters (Agm/ATT-Au NCs) as a novel electrochemiluminescence (ECL) illuminant, which exhibited high ECL in the annihilation path via the newly defined urface harge edistribution-nduced ECL nhancement (SCRIE). Impressively, the electrochemical redox reaction of Agm/ATT-Au NCs was enhanced owing to the boosted electron transfer kinetics of the illuminant by the positively charged Agm-triggered surface charge redistribution of ATT-Au NCs, resulting in an ∼110-fold higher ECL signal of Agm/ATT-Au NCs than ATT-Au NCs. This work digs deep into the electrogenerated process of the annihilation mechanism to direct the rational design of an efficient illuminant.

A High-Efficiency Autocatalysis-Oriented Cascade Circuit via Reciprocal Hug-Amplification for Assay-to-Treat Application.

Developing a DNA autocatalysis-oriented cascade circuit (AOCC) via reciprocal navigation of two enzyme-free hug-amplifiers might be desirable for constructing a rapid, efficient, and sensitive assay-to-treat platform. In response to a specific trigger (), seven functional DNA hairpins were designed to execute three-branched assembly (TBA) and three isotropic hybridization chain reaction (3HCR) events for operating the AOCC. This was because three new inducers were reconstructed in TBA arms to initiate 3HCR (TBA-to-3HCR) and periodic repeats were resultantly reassembled in the tandem nicks of polymeric nanowires to rapidly activate TBA in the opposite direction (3HCR-to-TBA) without steric hindrance, thereby cooperatively manipulating sustainable AOCC progress for exponential hug-amplification (1:3).

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.

Zinc-Organic Gel with Self-Catalysis-Enhanced Electrochemiluminescence as an Emitter for the Evaluation of Liver Cancer Markers.

Herein, a novel zinc-organic gel with self-catalysis-enhanced electrochemiluminescence (ECL) performance was prepared as an emitter for the first time to assemble a biosensor for ultrasensitive detection of microRNA-221 (miR-221) related to liver cancer. Interestingly, Zn served as a central ion to coordinate with multidentate ligands 2,4,6-tris(4-carboxyphenyl)-1,3,5-triazine (TATB) at room temperature to form Zn-TATB-MOGs with excellent ECL intensity. More importantly, compared to metal ions (e.

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.

Electron-Accelerator-Induced Fast Electron Transfer for Enhancing Electrochemiluminescence of Gold Nanoclusters and Its Bioanalysis Application: A Novel Avenue for Developing High-Efficient Emitters.

Herein, the gold nanoclusters/CaFeO nanospheres (Au NCs/CaFeO) heterostructure as a novel electrochemiluminescence (ECL) emitter was developed. Excitingly, Au NCs/CaFeO displayed highly efficient and greatly stable ECL based on the newly defined electron-accelerator p-type semiconductor CaFeO NS-induced fast electron transfer; it solved one key obstacle of metal NC-based ECL emitters: sluggish through-covalent bond electron transport kinetics-caused inferior ECL performance. Specifically, on account of the energy level matching between emitter Au NCs and electron-accelerator CaFeO NSs, the valence band (VB) of the electron-accelerator could provide abundant holes for rapidly transporting the electrogenerated electron from the highest occupied molecular orbital (HOMO) of Au NCs to the electrode, generating massive excited species of Au NCs for strong ECL emission.

High-Efficient Electrochemiluminescence of DNA-Au Ag Nanoclusters with Au NPs@TiC as a Novel Coreaction Accelerator for Ultrasensitive Biosensing.

In this work, an ultrasensitive electrochemiluminescence (ECL) biosensor was constructed based on DNA-stabilized Au Ag nanoclusters (DNA-Au Ag NCs) as the efficient luminophore and Au NPs@TiC as a new coreaction accelerator for determining microRNA-221 (miRNA-221) related to liver cancer. Impressively, DNA-Au Ag NCs were stabilized by the high affinity of the periodic 3C sequence, exhibiting an excellent ECL efficiency of 27% compared with classical BSA-Au Ag NCs (16%). Moreover, the Au NPs@TiC nanocomposites, as a new coreaction accelerator, were first introduced to accelerate the production of abundant sulfate free radicals (SO) for promoting the ECL efficiency of DNA-Au Ag NCs in the DNA-Au Ag NCs/Au NPs@TiC/SO ternary system due to the energy band of Au NPs@TiC being well-matched with the frontier orbital of SO.

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.

CsPbBr Perovskite Quantum Dots Encapsulated by a Polymer Matrix for Ultrasensitive Dynamic Imaging of Intracellular MicroRNA.

Herein, CsPbBr perovskite quantum dots (CPB PQDs)@poly(methyl methacrylate) (PMMA) (CPB@PMMA) nanospheres were used as energy donors with high Förster resonance energy transfer (FRET) efficiency and exceptional biocompatibility for ultrasensitive dynamic imaging of tiny amounts of microRNAs in living cells. Impressively, compared with traditional homogeneous single QDs as energy donors, CPB@PMMA obtained by encapsulating numerous CPB PQDs into PMMA as energy donors could not only significantly increase the efficiency of FRET via improving the local concentration of CPB PQDs but also distinctly avoid the problem of cytotoxicity caused by divulged heavy metal ions entering living cells. Most importantly, in the presence of target miRNA-21, DNA dendrimer-like nanostructures labeled with 6-carboxy-tetramethylrhodamine (TAMRA) were generated by the exposed tether interhybridization of the Y-shape structure, which could wrap around the surface of CPB@PMMA nanospheres to remarkably bridge the distance of FRET and increase the opportunity for effective energy transfer, resulting in excellent precision and accuracy for ultrasensitive and dynamic imaging of miRNAs.

Dual-Ligand Ruthenium Coordination Polymer-Derived Self-Enhanced Electrochemiluminescent Emitters for Sensitive Detection of Procalcitonin.

Ru-based electrochemiluminescence (ECL) coordination polymers are widely employed for bioanalysis and medical diagnosis. However, commonly used Ru-based coordination polymers face the limitation of low efficiency due to the long distance between the ECL reagent and the coreactant dispersed in detecting solution. Herein, we report a dual-ligand self-enhanced ECL coordination polymer, composed of tris(4,4'-dicarboxylic acid-2,2'-bipyridyl) ruthenium(II) dichloride (Ru(dcbpy)) as ECL reactant ligand and ethylenediamine (EDA) as corresponding coreactant ligand into Zn metal node, termed Zn-Ru-EDA.

Dual-sensitized heterojunction AgS/ZnS/NiS composites with entire visible-light region absorption for ultrasensitive photoelectrochemical detection of tobramycin.

In this study, an ultrasensitive photoelectrochemical (PEC) aptasensor based on dual-sensitized heterojunction AgS/ZnS/NiS composites as a signal probe was proposed for the detection of tobramycin (TOB) by combining a cascaded quadratic signal amplification strategy. Specifically, compared to the limited visible light-harvesting capability of single sensitized composites, AgS/ZnS/NiS composites with p-n and n-n heterojunction could greatly improve the light energy utilization to tremendously strengthen the optical absorption in the entire visible-light region. Moreover, dual-sensitized heterojunction could effectively hinder the rapid recombination of photoelectrons and holes (carriers) to obtain a good photocurrent for improving the sensitivity of the aptasensor.

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.

Ultrahigh-Speed 3D DNA Walker with Dual Self-Protected DNAzymes for Ultrasensitive Fluorescence Detection and Intracellular Imaging of microRNA.

Herein, a dual self-protected DNAzyme-based 3D DNA walker (dSPD walker), composed of activated dual self-protected walking particles (ac-dSPWPs) and track particles (TPs), was constructed for ultrasensitive and ultrahigh-speed fluorescence detection and imaging of microRNAs (miRNAs) in living cells. Impressively, compared with the defect that "one" target miRNA only initiates "one" walking arm of the conventional single self-protected DNAzyme walker, the dSPD walker benefits from the secondary amplification and spatial confinement effect and could guide "one" target miRNA to generate "" secondary targets, thereby initiating "" nearby walking strands immediately, realizing the initial rate over one-magnitude-order faster than that of the conventional one. Moreover, in the process of relative motion between ac-dSPWPs and TPs, the ac-dSPWPs could cleave multiple substrate strands simultaneously to speed up movement and reduce the derailment rate, as well as combine with successive TPs to facilitate a large amount of continuous signal accumulation, achieving an ultrafast detection of miRNA-221 within 10 min and high sensitivity with a low detection limit of 0.

A Fluorescence Light-Up 3D DNA Walker Driven and Accelerated by Endogenous Adenosine-5'-triphosphate for Sensitive and Rapid Label-Free MicroRNA Detection and Imaging in Living Cells.

Herein, a fluorescence light-up 3D DNA walker (FLDW) was powered and accelerated by endogenous adenosine-5'-triphosphate (ATP) molecules to construct a biosensor for sensitive and rapid label-free detection and imaging of microRNA-221 (miRNA-221) in malignant tumor cells. Impressively, ATP as the driving force and accelerator for FLDW could significantly accelerate the operation rate of FLDW, reduce the likelihood of errors in signaling, and improve the sensitivity of detection and imaging. When FLDW was initiated by output DNA H1-op transformed by target miRNA-221, G-rich sequences in the S strand, anchored to AuNP, were exposed to form G-quadruplexes (G4s), and thioflavin T (ThT) embedded in the G4s emitted intense fluorescence to realize sensitive and rapid detection of target miRNA-221.