Electrochemical Self-Sacrificial Label Conversion Coupled with DNA Framework Nanomachine Mediated Serotonin Sensing with Highly Minimized Background Noise.

Conventional solid/liquid electrochemical interfaces typically encounter challenges with impeded mass transport for poor electrochemical quantification due to the intricate pathways of reactants from the bulk solution. To address this issue, this work reports an innovative approach integrating a target-activated DNA framework nanomachine with electrochemically driven metal-organic framework (MOF) conversion for self-sacrificial biosensing. The presence of the target biomarker serotonin initiates the DNA framework nanomachine by an entropy-driven circuit to form a cross-linked nanostructure and subsequently release the Fe-MOF probe.

Programmable DNA Nanomachine Integrated with Electrochemically Controlled Atom Transfer Radical Polymerization for Antibody Detection at Picomolar Level.

The quantitative detection of antibodies is crucial for the diagnosis of infectious and autoimmune diseases, while the traditional methods experience high background signal noise and restricted signal gain. In this work, we have developed a highly efficient electrochemical biosensor by constructing a programmable DNA nanomachine integrated with electrochemically controlled atom transfer radical polymerization (eATRP). The sensor works by binding the target antidigoxin antibody (anti-Dig) to the epitope of the recognization probe, which then initiates the cascaded strand displacement reaction on a magnetic bead, leading to the capture of cupric oxide (CuO) nanoparticles through magnetic separation.

Two-step resonance-energy-transfer-based ratiometric biosensor for sensing and annihilation of .

A two-step resonance energy transfer (RET)-based fluorescence/electrochemiluminescence (FL/ECL) biosensor was developed for ratiometric measurement and annihilation of (). Using coupled dual-recognition-triggered target conversion with the catalytic hairpin assembly (CHA) technique, the monitoring of was obtained at the single-cell level.

An amplified logic gate driven by synthesis of silver nanoclusters for identification of biomarkers.

An amplified DNA logic sensor was constructed for the identification of multiple biomarkers, in which the inputs of targets triggered the disassembly of a V-shaped probe (VSP) structure by a strand displacement reaction, leading to the synthesis of silver nanoclusters (AgNCs) for electrocatalytic reduction of HO. The sensing platform achieved sensitive detection of methylated DNA and microRNA 122 with detection limits down to 3.4 and 4.

Wedged DNA Walker Coupled with a Bimetallic Metal-Organic Framework Electrocatalyst for Rapid and Sensitive Monitoring of DNA Methylation.

The dissociation of the walking strand from the track gives rise to decreased efficiency and long reaction time of DNA walkers. In this work, we constructed a DNA walker combining the introduction of a wedge segment with a bimetallic metal-organic framework (MOF) electrocatalyst to solve this problem. The target methylated DNA acted as a single-legged walker, and the immobilization probe assembled on the track contained a wedge segment that was complementary to the target methylated DNA persistently, inhibiting its dissociation from the track.

Cross-triggered and cascaded recycling amplification system for electrochemical detection of circulating microRNA in human serum.

A cross-triggered and cascaded recycling amplification system was developed for electrochemical sensing of microRNA 122 based on the DNAzyme/multicomponent nucleic acid enzyme cleavage technique and a dumbbell-shaped probe. The linear range and detection limit were obtained to be 1 fM-100 pM and 0.34 fM, respectively.

Label-free and enzyme-free fluorescence detection of microRNA based on sulfydryl-functionalized carbon dots via target-initiated hemin/G-quadruplex-catalyzed oxidation.

Carbon dots (CDs)-based biosensors have attracted considerable interest in reliable and sensitive detection of microRNA (miRNA) because of their merits of ultra-small size, excellent biosafety and tunable emission, whereas complicated labeling procedure and expensive bioenzyme associated with current strategies significantly limit their practical application. Herein, we developed a label-free and enzyme-free fluorescence strategy based on strand displaced amplification (SDA) for highly sensitive detection of miRNA using sulfydryl-functionalized CDs (CDs-SH) as probe. CDs-SH displayed excellent response to G-quadruplex DNA against other DNAs based on based on the catalytic oxidation of -SH into -S-S- by hemin/G-quadruplex.

Construction of an Electrochemical Biosensing Platform Based on Hierarchical Mesoporous NiO@N-Doped C Microspheres Coupled with Catalytic Hairpin Assembly.

A critical challenge for improving the detection performance of sensors is building a favorable sensing interface. Herein, an innovative electrochemical biosensing system relying on hierarchical mesoporous NiO@N-doped C microspheres coupled with catalytic hairpin assembly was developed for DNA analysis. In this strategy, the utilization of NiO@N-doped C microspheres and multiwalled carbon nanotubes as electrode materials effectively enhanced the interfacial electron transfer and improved the surface active sites for subsequent reactions.

Aptamer-Functionalized and Gold Nanoparticle Array-Decorated Magnetic Graphene Nanosheets Enable Multiplexed and Sensitive Electrochemical Detection of Rare Circulating Tumor Cells in Whole Blood.

The identification and monitoring of circulating tumor cells (CTCs) in human blood plays a pivotal role in the convenient diagnosis of different cancers. However, it remains a major challenge to monitor these CTCs because of their extremely low abundance in human blood. Here, we describe the synthesis of a new aptamer-functionalized and gold nanoparticle (AuNP) array-decorated magnetic graphene nanosheet recognition probe to capture and isolate rare CTCs from human whole blood.

DNA-Templated In Situ Synthesis of Highly Dispersed AuNPs on Nitrogen-Doped Graphene for Real-Time Electrochemical Monitoring of Nitric Oxide Released from Live Cancer Cells.

Dispersion promotion of nanomaterials can significantly enhance their catalytic activities. With a new DNA-templated in situ synthesis approach, we report the preparation of highly dispersed AuNPs on nitrogen-doped graphene sheets (NGS) with significantly improved electrocatalytic ability for the monitoring of nitric oxide (NO) released from live cancer cells. The template DNA is adsorbed on NGS via π-π stacking, and the Au precursor chelates along the DNA lattice through dative bonding.

Electrochemical screening of single nucleotide polymorphisms with significantly enhanced discrimination factor by an amplified ratiometric sensor.

The detection of single nucleotide polymorphisms (SNPs) is of great clinical significance to the diagnosis of various genetic diseases and cancers. In this work, the development of an ultrasensitive ratiometric electrochemical sensor for screening SNP with a significantly enhanced discrimination factor is reported. The ferrocene (Fc) and methylene blue (MB) dual-tagged triple helix complex (THC) probes are self-assembled on the gold electrode to construct the sensing interface.

Trimetallic Hybrid Nanoflower-Decorated MoS Nanosheet Sensor for Direct in Situ Monitoring of HO Secreted from Live Cancer Cells.

In situ monitoring of hydrogen peroxide (HO) secreted from live cells plays a critical role in elucidating many cellular signaling pathways, and it is a significant challenge to selectively detect these low levels of endogenous HO. To address this challenge, we report the establishment of a trimetallic hybrid nanoflower-decorated MoS nanosheet-modified sensor for in situ monitoring of HO secreted from live MCF-7 cancer cells. The Au-Pd-Pt nanoflower-dispersed MoS nanosheets are synthesized by a simple wet-chemistry method, and the resulting nanosheet composites exhibit significantly enhanced catalytic activity toward electrochemical reduction of HO, due to the synergistic effect of the highly dispersed trimetallic hybrid nanoflowers and the MoS nanosheets, thereby resulting in ultrasensitive detection of HO with a subnanomolar level detection limit in vitro.

Aptamer/Protein Proximity Binding-Triggered Molecular Machine for Amplified Electrochemical Sensing of Thrombin.

The development of convenient and sensitive methods without involving any enzymes or complex nanomaterials for the monitoring of proteins is of great significance in disease diagnostics. In this work, we describe the validation of a new aptamer/protein proximity binding-triggered molecular machinery amplification strategy for sensitive electrochemical assay of thrombin in complex serum samples. The sensing interface is prepared by self-assembly of three-stranded DNA complexes on the gold electrode.

Target-triggered catalytic hairpin assembly and TdT-catalyzed DNA polymerization for amplified electronic detection of thrombin in human serums.

Specific and sensitive detection of protein biomarkers is of great importance in biomedical and bioanalytical applications. In this work, a dual amplified signal enhancement approach based on the integration of catalytic hairpin assembly (CHA) and terminal deoxynucleotidyl transferase (TdT)-mediated in situ DNA polymerization has been developed for highly sensitive and label-free electrochemical detection of thrombin in human serums. The presence of the target thrombin leads to the unfolding and capture of a significant number of hairpin signal probes with free 3'-OH termini on the sensor electrode.

Proximity Binding and Metal Ion-Dependent DNAzyme Cyclic Amplification-Integrated Aptasensor for Label-Free and Sensitive Electrochemical Detection of Thrombin.

Thrombin plays important roles for the diagnosis of neurodegenerative and cardiovascular diseases. By integrating proximity binding-induced strand displacement and metal ion-dependent DNAzyme recycling amplification, we demonstrate here the development of a simple and sensitive strategy for the detection of thrombin in human serums. The binding of the two distinct aptamers to the thrombin targets increases the local concentration of the aptamers and facilitates the release of the enzymatic sequences through proximity binding-induced strand displacement.

Cross-triggered and cascaded recycling amplification for ultrasensitive electrochemical sensing of the mutant human p53 gene.

Based on an endonuclease-assisted, cross-triggered and cascaded recycling amplification strategy, the construction of a simple electrochemical sensing platform for the ultrasensitive detection of the mutant p53 gene in human serum is described. Using this new signal amplification approach, the sub-femtomolar level of the mutant p53 gene can be selectively detected.

DNA-mediated strand displacement facilitates sensitive electronic detection of antibodies in human serums.

We describe here the development of a sensitive and convenient electronic sensor for the detection of antibodies in human serums. The sensor is constructed by self-assembly formation of a mixed monolayer containing the small molecule epitope conjugated double stranded DNA probes on gold electrode. The target antibody binds the epitope on the dsDNA probe and lowers the melting temperature of the duplex, which facilitates the displacement of the antibody-linked strand of the duplex probe by an invading methylene blue-tagged single stranded DNA (MB-ssDNA) through the strand displacement reaction and leads to the capture of many MB-ssDNA on the sensor surface.

Cascaded strand displacement for non-enzymatic target recycling amplification and label-free electronic detection of microRNA from tumor cells.

The monitoring of microRNA (miRNA) expression levels is of great importance in cancer diagnosis. In the present work, based on two cascaded toehold-mediated strand displacement reactions (TSDRs), we have developed a label- and enzyme-free target recycling signal amplification approach for sensitive electronic detection of miRNA-21 from human breast cancer cells. The junction probes containing the locked G-quadruplex forming sequences are self-assembled on the senor surface.

DNA-fueled molecular machine enables enzyme-free target recycling amplification for electronic detection of microRNA from cancer cells with highly minimized background noise.

The variations in microRNA (miRNA) expression levels can be useful biomarkers for the diagnosis of different cancers. In this work, on the basis of a new miRNA-triggered molecular machine for enzyme-free target recycling signal amplification, the development of a simple electronic sensor for highly sensitive detection of miRNA-21 from human breast cancer cells is described. The three-stand DNA duplex probes are self-assembled on the gold electrode surface to fabricate the sensor.

Target-induced reconfiguration of DNA probes for recycling amplification and signal-on electrochemical detection of hereditary tyrosinemia type I gene.

By coupling target DNA-induced reconfiguration of the dsDNA probes with enzyme-assisted target recycling amplification, we describe the development of a signal-on electrochemical sensing approach for sensitive detection of hereditary tyrosinemia type I gene. The dsDNA probes are self-assembled on the sensing electrode, and the addition of the target DNA reconfigures and switches the dsDNA probes into active substrates for exonuclease III, which catalytically digests the probes and leads to cyclic reuse of the target DNA. The target DNA recycling and the removal of one of the ssDNA from the dsDNA probes by exonuclease III result in the formation of many hairpin structures on the sensor surface, which brings the electroactive methylene blue labels into proximity with the electrode and produces a significantly amplified current response for sensitive detection of the target gene down to 0.

In situ DNA-templated synthesis of silver nanoclusters for ultrasensitive and label-free electrochemical detection of microRNA.

On the basis of the use of silver nanoclusters (AgNCs) in situ synthesized by cytosine (C)-rich loop DNA templates as signal amplification labels, the development of a label-free and highly sensitive method for electrochemical detection of microRNA (miRNA-199a) is described. The target miRNA-199a hybridizes with the partial dsDNA probes to initiate the target-assisted polymerization nicking reaction (TAPNR) amplification to produce massive intermediate sequences, which can be captured on the sensing electrode by the self-assembled DNA secondary probes. These surface-captured intermediate sequences further trigger the hybridization chain reaction (HCR) amplification to form dsDNA polymers with numerous C-rich loop DNA templates on the electrode surface.

Multiplexed and amplified electronic sensor for the detection of microRNAs from cancer cells.

The detection of microRNA expression profiles plays an important role in early diagnosis of different cancers. On the basis of the employment of redox labels with distinct potential positions and duplex specific nuclease (DSN)-assisted target recycling signal amplifications, we have developed a multiplexed and convenient electronic sensor for highly sensitive detection of microRNA (miRNA)-141 and miRNA-21. The sensor is constructed by self-assembly of thiol-modified, redox species-labeled hairpin probes on the gold sensing electrode.