A novel metal-organic framework loaded with abundant N-(aminobutyl)-N-(ethylisoluminol) as a high-efficiency electrochemiluminescence indicator for sensitive detection of mucin1 on cancer cells.

Herein, a high-efficiency electrochemiluminescence (ECL) indicator of an abundant N-(aminobutyl)-N-(ethylisoluminol) functionalized metal-organic framework (ABEI@Fe-MIL-101) was synthesized to construct a biosensor for the ultrasensitive assay of mucin1 on MCF-7 cancer cells with a coreactant HO-free strategy.

A Peptide Cleavage-Based Ultrasensitive Electrochemical Biosensor with an Ingenious Two-Stage DNA Template for Highly Efficient DNA Exponential Amplification.

The direct transduction of a peptide cleavage event into DNA detection has always produced output DNA with some amino acid residues, which influence the DNA amplification efficiency in view of their steric hindrance effect. Here an ingenious two-stage DNA template was designed to achieve highly efficient DNA amplification by utilizing the DNA exponential amplification reaction (EXPAR) as a model. The usage of a two-stage DNA template not only accomplished the traditionally inefficient EXPAR triggered by output DNA with some amino acid residues but also simultaneously produced a newly identical DNA trigger without any amino acid residues to induce an extra efficient EXPAR, which significantly improved the DNA amplification efficiency, realizing the ultrasensitive detection of the target.

Ternary Electrochemiluminescence System Based on Rubrene Microrods as Luminophore and Pt Nanomaterials as Coreaction Accelerator for Ultrasensitive Detection of MicroRNA from Cancer Cells.

As the only endogenous coreactant in the electrochemiluminescence (ECL) system, the dissolved O was the ideal candidate due to the mild reaction and easy operation, but compared to SO, the dissolved O with weaker redox activity suffers from the poor enhancement effect of the luminophore, which restricted the further application in bioanalysis. Here, a high-intense ECL signal was gained by the employing of Pt nanomaterials as a coreaction accelerator to generate more of the intermediate of dissolved O to promote the coreaction efficiency. On the basis of a new ternary ECL system of Pt nanomaterials as the coreaction accelerator, dissolved O as the coreactant, and a neotype rubrene microrods as the luminophore, an efficient "on-off-on" solid-state ECL switch platfrom was designed for ultrasensitive microRNA (miRNA) detection with a background reduction strategy of ferrocene-labeled single-stranded DNA (Fc-DNA) as a quencher.

Hollow Porous Polymeric Nanospheres of a Self-Enhanced Ruthenium Complex with Improved Electrochemiluminescent Efficiency for Ultrasensitive Aptasensor Construction.

Although Ru(II)-complex-based bulk nanomaterials have received considerable attention in electrochemiluminescent (ECL) assays owing to their strong ECL signals, the ECL efficiency of these nanomaterials was quite low since the bulk nanomaterials brought about a serious inner filter effect and excess inactive emitters. Herein, hollow porous polymeric nanospheres of a self-enhanced ruthenium complex (abbreviated as Ru-HPNSs) were prepared with a polyethylenimine-ruthenium complex precursor to greatly decrease the inner filter effect and minimize inactive emitters, which significantly improved the ECL efficiency. On the basis of the novel Ru-HPNSs as efficient ECL tags and target-catalyzed hairpin hybridization as signal amplification strategy, an ultrasensitive ECL aptasensor was constructed for the detection of mucin 1 (MUC1), which showed excellent linear response to a concentration variation from 1.

Universal Ratiometric Photoelectrochemical Bioassay with Target-Nucleotide Transduction-Amplification and Electron-Transfer Tunneling Distance Regulation Strategies for Ultrasensitive Determination of microRNA in Cells.

A universal ratiometric photoelectrochemical (PEC) bioassay, which could be readily expanded for ultrasensitive determination of various targets in complex biological matrixes, was established by coupling a target-nucleotide transduction-amplification with DNA nanomachine mediated electron-transfer tunneling distance regulation strategies. With the help of target-nucleotide transduction-amplification strategy, the one input target signal could be transducted to corresponding multiple output DNA signals by nucleotide specific recognition technology, simultaneously leading to an efficient signal amplification for target. Then the output DNA could initiate the formation of four-way junction DNA nanomachine through binding-induced combination, by which the electron-transfer tunneling distance between photoactive materials and sensing interface could be regulated, simultaneously resulting an enhanced photocurrent signal from SiO@methylene blue (SiO@MB) as wavelength-selective photoactive material in close proximity to sensing interface and a reduced photocurrent signal from another wavelength-selective photoactive material CdS quantum dots (CdS QDs) away from sensing interface for photocurrent signal ratio calculation.

Switchable Target-Responsive 3D DNA Hydrogels As a Signal Amplification Strategy Combining with SERS Technique for Ultrasensitive Detection of miRNA 155.

Usually, SERS technology requires labeling of the Raman reporter to obtain characteristic spectra for detection of biological samples. However, the number of labeled Raman reporters is often limited, resulting in the restricted improvement for sensitivity of SERS biosensor. In this work, switchable target-responsive 3D DNA hydrogels were introduced to precisely control trapping and release of Raman reporter toluidine blue (TB), which not only avoid labeling signal molecule but also improve the sensitivity of miRNA detection due to immobilization of abundant TB.

Host-Guest Recognition-Assisted Electrochemical Release: Its Reusable Sensing Application Based on DNA Cross Configuration-Fueled Target Cycling and Strand Displacement Reaction Amplification.

In this work, an elegantly designed host-guest recognition-assisted electrochemical release was established and applied in a reusable electrochemical biosensor for the detection of microRNA-182-5p (miRNA-182-5p), a prostate cancer biomarker in prostate cancer, based on the DNA cross configuration-fueled target cycling and strand displacement reaction (SDR) amplification. With such a design, the single target miRNA input could be converted to large numbers of single-stranded DNA (S1-Trp and S2-Trp) output, which could be trapped by cucurbit[8]uril methyl viologen (CB-8-MV) based on the host-guest recognition, significantly enhancing the sensitivity for miRNA detection. Moreover, the nucleic acids products obtained from the process of cycling amplification could be utilized sufficiently, avoiding the waste and saving the experiment cost.

PtNPs as Scaffolds to Regulate Interenzyme Distance for Construction of Efficient Enzyme Cascade Amplification for Ultrasensitive Electrochemical Detection of MMP-2.

The high catalytic efficiency of enzyme cascade reaction mainly depends on optimal interenzyme distance regulated by the special scaffolds. In this work, the rigid PtNPs with different sizes were employed as scaffolds to regulate interenzyme distance for efficient enzyme cascade amplification to construct electrochemical biosensor for sensitive detection of matrix metalloproteinases-2 (MMP-2), which overcame the drawbacks of instable construction and sophisticated preparation induced by conventional scaffolds such as metal-organic frameworks (MOFs), DNA nanostructures. Here, cucurbit[7]uril functionalized PtNPs (CB[7]@PtNPs) was utilized to load ferrocene (Fc)-labeled horseradish peroxidase (HRP) and glucose oxidase (GOx) via host-guest interaction between Fc and CB[7], respectively, resulting in the formation of a stable three-dimensional netlike structure containing amounts of enzymes.

Ultrasensitive Electrochemiluminescence Biosensor for MicroRNA Detection by 3D DNA Walking Machine Based Target Conversion and Distance-Controllable Signal Quenching and Enhancing.

In this study, an electrochemiluminescence (ECL) regenerated biosensor was reported to sensitively detect microRNA through 3D DNA walking machine and "on-off-super on" strategy. First, 3D DNA walking machine with higher efficiency of payload releasing and superior signal amplification than those of the traditional DNA walking machine was initially introduced in the ECL system for converting target microRNA to intermediate DNA and achieving significant signal amplification. Second, the distance between CdS:Mn quantum dots and Au nanoparticles was increased with the hybridization of intermediate DNA and Au nanoparticles modified S2, which weakened the energy transfer for ECL signal recovering and excited the surface plasma resonance for further enhancing the signal to construct the on-off-super on biosensor.

MoS Quantum Dots as New Electrochemiluminescence Emitters for Ultrasensitive Bioanalysis of Lipopolysaccharide.

Cd-based semiconductor quantum dots (QDs) with size-tunable luminescence and high quantum yield have become the most promising electrochemiluminescence (ECL) emitters. However, their unavoidable biotoxicity limited their applications in bioassays. Here, the nontoxic and economical MoS QDs prepared by chemical exfoliation from the bulk MoS were first investigated as new ECL emitters, and then the possible luminescence mechanism of MoS QDs was studied using ECL-potential curves and differential pulse voltammetry (DPV) methods in detail.

Highly effective molecule converting strategy based on enzyme-free dual recycling amplification for ultrasensitive electrochemical detection of ATP.

An enzyme-free and highly effective molecule converting strategy based on target-driven catalytic hairpin assembly and Mg-dependent DNAzyme recycling dual-amplification was proposed to construct an ultrasensitive electrochemical biosensor for adenosine triphosphate (ATP) detection.

An efficient electrochemiluminescence amplification strategy via bis-co-reaction accelerator for sensitive detection of laminin to monitor overnutrition associated liver damage.

With the world wildly improvement in dietary and nutrition status, it couldn't be ignored that the chronic liver disease (CLD) resulted from the overnutrition. In order to estimate nutrition status for healthy living, an efficient and sensitive electrochemiluminescence (ECL) sandwich immunosensor of laminin (LN), a marker of CLD, was proposed for early diagnosis of CLD. In this work, the anodic ECL behavior of perylene derivative using HO as co-reactant was demonstrated and the possible ECL mechanism was proposed.

An efficient target-intermediate recycling amplification strategy for ultrasensitive fluorescence assay of intracellular lead ions.

An ultrasensitive fluorescence assay for intracellular Pb determination was proposed through target-intermediate recycling amplification based on metal-assisted DNAzyme catalysis and strand displacement reactions. Compared with only target recycling-based fluorescence assay with an M amplification ratio, the proposed assay could achieve an M × N amplification ratio to obtain an improved sensitivity by more than 10 times, in which M and N are the amplification ratios of target recycling and intermediate recycling, respectively. Remarkably, this proposed ultrasensitive fluorescence assay could be applied to the determination of various analytes with the well-designed detection probe, especially in intracellular assay, providing a promising tool for clinical diagnosis and biomedical detection.

In Situ Electrodeposited Synthesis of Electrochemiluminescent Ag Nanoclusters as Signal Probe for Ultrasensitive Detection of Cyclin-D1 from Cancer Cells.

Metal nanoclusters (NCs) as a new type of electrochemiluminescence (ECL) nanomaterials have attracted great attention, but their applications are limited due to relatively low luminescent efficiency and a complex preparation process. Herein, an ultrasensitive ECL biosensor for the detection of Cyclin-D1 (CCND1) was designed by utilizing in situ electrogenerated silver nanoclusters (AgNCs) as ECL emitters and FeO-CeO nanocomposites as a coreaction accelerator. The ECL luminous efficiency of AgNCs on the electrode could be significantly enhanced with the use of the FeO-CeO for accelerating the reduction of SO to generate the strong oxidizing intermediate radical SO.

K-junction structure mediated exponential signal amplification strategy for microRNA detection in electrochemiluminescence biosensor.

Based on the novel designed K-junction structure, an economic and efficient exponential signal amplification strategy with simple protocol combining hemin/G-quadruplex, a mimetic peroxidase, as a catalyzer was proposed and utilized in an electrochemiluminescence biosensor for sensitive microRNA detection. It was noteworthy that the K-junction structure was formed with guanine-rich reporter DNA and substrate DNA modified by phosphate at the 5'-terminus. Thus, the activity of the reporter DNA could be inhibited and the recognition domain for the target microRNA constructed through the K-junction structure formed.

Highly Efficient Electrochemiluminescence Resonance Energy Transfer System in One Nanostructure: Its Application for Ultrasensitive Detection of MicroRNA in Cancer Cells.

The electrochemiluminesce (ECL) efficiency of luminous emitter can be enhanced by the means of electrochemiluminesce resonance energy transfer (ECL-RET) with a matched donor. However, generally, the donor and acceptor pairs were separated in different independent nanostructures, experiencing the challenging issues of limited energy transfer efficiency and luminous stability. Herein, we designed novel ECL-RET model within one nanostructure containing the donor of tris(4,4'-dicarboxylicacid-2,2'-bipyridyl) ruthenium(II) dichloride (Ru(dcbpy)) and the acceptor of CdSe@ZnS quantum dots (QDs) for acting as the ECL emitter (QDs-Ru(dcbpy)), which significantly reduced the energy loss and improved the ECL efficiency of QDs because of the short path of energy transmission.

Competitive method-based electrochemiluminescent assay with protein-nucleotide conversion for ratio detection to efficiently monitor the drug resistance of cancer cells.

A simple and highly-efficient approach to monitor the expression of P-glycoprotein (P-gp) in cells was urgently needed to demonstrate the drug resistance of cancer cells. Herein, a competitive method-based electrochemiluminescent (ECL) assay with a single ECL indicator was proposed for the first time to efficiently estimate the concentration ratio of two proteins. By converting the different proteins to partially coincident nucleotide sequences a sandwich type immunoassay on magnetic beads, the concentration ratio related ECL signals could be obtained competitive nucleotide hybridization on an electrode surface.

Thrombin aptasensor enabled by Pt nanoparticles-functionalized Co-based metal organic frameworks assisted electrochemical signal amplification.

In this work, a Pt nanoparticles-functionalized Co-based metal organic frameworks (PtNPs@Co(II)MOFs@PtNPs) was synthesized and applied in electrochemical aptasensor for thrombin (TB) detection. First, the Co(II)MOFs@PtNPs were prepared via the mixed solvothermal method, which consists of inner Pt nanoparticles (PtNPs) encapsulated by aminofunctionalized Co(II)MOFs materials. Following that, additional PtNPs were adsorbed on the surface of Co(II)MOFs@PtNPs, resulting in the formation of PtNPs@Co(II)MOFs@PtNPs nanocomposite.

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.

A sensitive immunosensor via in situ enzymatically generating efficient quencher for electrochemiluminescence of iridium complexes doped SiO nanoparticles.

A sensitive electrochemiluminescent (ECL) sandwich immunosensor was proposed herein based on the tris (2-phenylpyridine) iridium [Ir(ppy)] doped silica nanoparticles (SiO@Ir) with improved ECL emission as signal probes and glucose oxidase (GOD)-based in situ enzymatic reaction to generate HO for efficiently quenching the ECL emission of SiO@Ir. Typically, the SiO@Ir not only increased the loading amount of Ir(ppy) as ECL indicators with high ECL emission, but also improved their water-solubility, which efficiently enhanced the ECL emission. Furthermore, by the efficient quench effect of HO from in situ glucose oxidase (GOD)-based enzymatic reaction on the ECL emission of SiO@Ir, a signal-off ECL immunsensor could be established for sensitive assay.

Bi-directional DNA Walking Machine and Its Application in an Enzyme-Free Electrochemiluminescence Biosensor for Sensitive Detection of MicroRNAs.

Herein, a dual microRNA (miRNA) powered bi-directional DNA walking machine with precise control was developed to fabricate an enzyme-free biosensor on the basis of distance-based electrochemiluminescence (ECL) energy transfer for multiple detection of miRNAs. By using miRNA-21 as the driving force, the DNA walker could move forth along the track and generated quenching of ECL response due to the proximity between Au nanoparticles (AuNPs) and Mn doped CdS nanocrystals (CdS:Mn NCs) film as the ECL emitters, realizing ultrasensitive determination of miRNA-21. Impressively, once miRNA-155 was introduced as the driving force, the walker could move back along the track automatically, and surface plasmon resonance (SPR) occurred owing to the appropriate large separation between AuNPs and CdS:Mn NCs, achieving an ECL enhancement and realizing ultrasensitive detection of miRNA-155.

Electrochemiluminescence Biosensor Based on 3-D DNA Nanomachine Signal Probe Powered by Protein-Aptamer Binding Complex for Ultrasensitive Mucin 1 Detection.

Herein, we fabricated a novel electrochemiluminescence (ECL) biosensor for ultrasensitive detection of mucin 1 (MUC1) based on a three-dimensional (3-D) DNA nanomachine signal probe powered by protein-aptamer binding complex. The assembly of 3-D DNA nanomachine signal probe achieved the cyclic reuse of target protein based on the protein-aptamer binding complex induced catalyzed hairpin assembly (CHA), which overcame the shortcoming of protein conversion with enzyme cleavage or polymerization in the traditional examination of protein. In addition, CoFeO, a mimic peroxidase, was used as the nanocarrier of the 3-D DNA nanomachine signal probe to catalyze the decomposition of coreactant HO to generate numerous reactive hydroxyl radical OH as the efficient accelerator of N-(aminobutyl)-N-(ethylisoluminol) (ABEI) ECL reaction to amplify the luminescence signal.

Highly Efficient Electrochemiluminescent Silver Nanoclusters/Titanium Oxide Nanomaterials as a Signal Probe for Ferrocene-Driven Light Switch Bioanalysis.

In this work, a ferrocene (Fc)-driven light switch biosensor for ultrasensitive detection of amyloid-β (Aβ) was designed by utilizing the highly efficient electrochemiluminescent nanomaterials of silver nanoclusters/titanium oxide nanoflowers (Ag NCs/TiO NFs) as signal labels. Through combining the TiO NFs as the coreaction accelerator and dissolved O as the intrinsic coreactant to in situ generate the strong oxidizing intermediate radical OH, the electrochemiluminescence (ECL) of Ag NCs on the TiO NFs surface could be significantly promoted in comparison with that of pure Ag NCs in solution. Further, Fc-labeled DNA as the ECL quenching probe was introduced to dramatically restrain the ECL emission of nanomaterials, which facilitated improving the sensitivity of the prepared biosensor to a large extent.

Ultrasensitive Assay for Telomerase Activity via Self-Enhanced Electrochemiluminescent Ruthenium Complex Doped Metal-Organic Frameworks with High Emission Efficiency.

Here, an ultrasensitive "off-on" electrochemiluminescence (ECL) biosensor was proposed for the determination of telomerase activity by using a self-enhanced ruthenium polyethylenimine (Ru-PEI) complex doped zeolitic imidazolate framework-8 (Ru-PEI@ZIF-8) with high ECL efficiency as an ECL indicator and an enzyme-assisted DNA cycle amplification strategy. The Ru-PEI@ZIF-8 nanocomposites were synthesized by self-enhanced Ru-PEI complex doping during the growth of zeolitic imidazolate framework-8 (ZIF-8), which presented high ECL efficiency and excellent stability. Furthermore, owing to the porosity of Ru-PEI@ZIF-8, the self-enhanced Ru-PEI complex in the outer layer and inner layer of self-enhanced Ru-PEI@ZIF-8 could be excited by electrons causing the utilization ratio of the self-enhanced ECL materials to be remarkably increased.

"Off" to "On" Surface-Enhanced Raman Spectroscopy Platform with Padlock Probe-Based Exponential Rolling Circle Amplification for Ultrasensitive Detection of MicroRNA 155.

In this work, an "off" to "on" surface-enhanced Raman spectroscopy (SERS) platform was constructed for ultrasensitive detection of microRNA (miRNA) by using a magnetic SERS substrate (Co@C/PEI/Ag) and padlock probe-based exponential rolling circle amplification (P-ERCA) strategy. Herein, miRNA 155 could act as primers to initiate rolling circle amplification (RCA) for producing a long repeat sequence, and then the obtained DNA would be cleaved into two kinds of single-stranded DNAs in the presence of nickase. One of the DNAs can be a new primer to initiate new cycle reactions for obtaining large numbers of the other one (trigger DNA), consequently leading to an exponential amplification.