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. Surprisingly, the surface-related ECL of Au NCs exhibits a wide color-tunable range of 625-829 nm, but the core-related ECL remains constant at 489 nm. Theoretical and experimental studies demonstrate that the color-tunable ECL is caused by the dynamic surface reconstruction of Au NCs and TEA radicals. This work opens up new avenues for dynamically manipulating the ECL spectra of core-shell emitters in biosensing and imaging research.

Insights of Life Molecules' Dynamic Distribution in Live Cells via Sequence-Structure Bispecific Fluorescent RNA.

Life molecules' distributions in live systems construct the complex dynamic reaction networks, whereas it is still challenging to demonstrate the dynamic distributions of biomolecules in live systems. Herein, we proposed a dynamic analysis strategy via sequence-structure bispecific RNA with state-adjustable molecules to monitor the dynamic concentration and spatiotemporal localization of these biomolecules in live cells based on the new insight of fluorescent RNA (FLRNA) interactions and their mechanism of fluorescence enhancement. Typically, computer-based nucleic acid-molecular docking simulation and molecular theoretical calculation have been proposed to provide a simple and straightforward method for guiding the custom-design of FLRNA. Impressively, a novel FLRNA with sequence and structure bispecific RNA named as a structure-switching aptamer (SSA) was introduced to monitor the real-time concentration and spatiotemporal localization of biomolecules, contributing to a deeper insight of the dynamic monitoring and visualization of biomolecules in live systems.

Pyrenecarboxaldehyde encapsulated porous TiO2 nanoreactors for monitoring cellular GSH levels.

Recently, ternary electrochemiluminescence (ECL) system has become a hot research topic due to its great potential for improving ECL efficiency by promoting the generation of intermediates. However, it is still a great challenge to increase the utilization rate of intermediates in a ternary ECL system. Herein, we propose a strategy to increase the utilization rate of intermediates by designing pyrenecarboxaldehyde (Pyc) encapsulated porous titania (pTiO2) nanospheres (Pyc@pTiO2) as ECL nanoreactors for an integrated ternary (luminophore/coreactant/co-reaction accelerator, Pyc/S2O82-/TiO2) ECL system construction. Specifically, pTiO2 acted as an ECL co-reaction accelerator, in which Pyc could obtain electrons from the conduction band of TiO2 to produce more SO4˙-, increasing its emissions. Simultaneously, pTiO2 could provide confined reaction spaces to effectively shorten the diffusion distance, extend the lifetime of free radicals, increase the utilization rate of intermediates and improve the efficiency of the ternary ECL system. As a proof of concept, the Pyc@pTiO2 nanoreactors-based sensing platform was successfully constructed to sensitively monitor cellular GSH levels. Overall, this work for the first time proposed an avenue to increase the utilization rate of intermediates in a ternary ECL system, which opened a new route for ECL biosensing in cell analysis applications.

In Situ Controllable Generation of Copper Nanoclusters Confined in a Poly-l-Cysteine Porous Film with Enhanced Electrochemiluminescence for Alkaline Phosphatase Detection.

Copper nanoclusters (Cu NCs) as emerging luminescent metal NCs are gaining increasing attention owing to the comparatively low cost and high abundance of the Cu element in nature. However, it remains challenging to manipulate the optical properties of Cu NCs. Unlike most dispersed Cu NCs, whose luminescence efficiency was restricted by nonexcited relaxation, the Cu NCs confined in a porous poly-l-cysteine (poly-l-Cys) film were generated controllably with enhanced electrochemiluminescence (ECL) by in situ electrochemical reduction. Specifically, poly-l-Cys provided a porous structure to regulate the generation of Cu NCs within its holes, which not only increased the restriction on the intramolecular vibration and rotation of the ligands but also expedited the electron transfer near the electrode surface, reflecting in an enhancement of the ECL signal and efficiency. As an application of the confined Cu NCs, an ECL biosensor with high performance was constructed skillfully for highly sensitive detection of alkaline phosphatase (ALP), which adopted Cu NCs as the ECL luminophore and poly-l-Cys as a coreaction accelerator in a novel ECL ternary system (Cu NCs/S2O82-/poly-l-Cys). Furthermore, an ingenious target amplification based on the combination of a DNA walker and click chemistry was developed to convert ALP to DNA strands efficiently, achieving great improvement in the recognition efficiency. As a result, the biosensor had a low detection limit (9.5 × 10-7 U·L-1) and a wide linear range (10-8-10-2 U·L-1) for ALP detection, which showed great promise for the detection of non-nucleic acid targets and the diagnosis of diseases.

Tetrakis(4-aminophenyl) ethene-doped perylene microcrystals with strong electrochemiluminescence for biosensing applications.

Perylene and its derivatives, as classical organic polycyclic aromatic hydrocarbon (PAH) ECL materials, have attracted extensive attention due to their excellent photoelectric activity and good structural controllability. As is well-known, the molecular structure of perylene is composed of five coplanar aromatic rings. There are intense π-π stacking interactions between perylene molecules, which lead to their aggregation and poor solubility in aqueous media. Unfortunately, this aggregation can weaken or even quench the emission intensity of perylene owing to the aggregation-caused quenching (ACQ) effect, finally limiting the analytical application of perylene in biological detection. In this work, perylene composite microcrystals (ETTA@Pe MCs) doped with non-planar molecular tetrakis(4-aminophenyl)ethene were synthesized in the aqueous phase by a surfactant-assisted self-assembly method. During this process, the intense π-π stacking interactions between perylene monomers were suppressed by doping. As a result, the ETTA@Pe MCs exhibited a significantly enhanced ECL signal as compared to that of perylene microcrystals (Pe MCs) in the presence of S2O82- as a co-reactant. Moreover, the ETTA@Pe MCs were utilized as a novel electrochemiluminescent (ECL) luminophores to fabricate a sensitive ECL biosensor for the quantitative analysis of dopamine (DA), which displayed a favorable linear response from 1 to 100 µmol L-1 with a detection limit of 0.96 nmol L-1.

Pore Confinement-Enhanced Electrochemiluminescence on SnO2 Nanocrystal Xerogel with NO3- As Co-Reactant and Its Application in Facile and Sensitive Bioanalysis.

Herein, 10-fold electrochemiluminescence (ECL) enhancement from a porous SnO2 nanocrystal (SnO2 NC) xerogel (vs discrete SnO2 NCs) was first observed with NO3- as a novel coreactant. This new booster phenomenon caused by pore characteristic was defined as "pore confinement-induced ECL enhancement", which originated from two possible reasons: First, the SnO2 NC xerogel with hierarchically porous structure could not only localize massive luminophore near the electrode surface, more importantly, but could accelerate the electrochemical and chemiluminescence reaction efficiency because the pore channels of xerogel could promote the mass transport and electron transfer in the confined spaces. Second, the NO3- could be in situ reduced easily to the active nitrogen species by means of the pore confinement effect, which could be served as a new coreactant for nanocrystal-based ECL amplification with the excellent stability and good biocompatibility. As a proof of concept, a facile and sensitive sensing platform for SO32- detection has been successfully constructed upon effectively quenching of SO32- toward the SnO2 NC xerogel/NO3- ECL system. The key feature about this work presented a grand avenue to achieve the strong ECL signal, especially from weak emitters, which gave a fresh impetus to the construction of new-generation of surface-confined ECL platform with potential applications in ECL imaging and sensing.

Organic Dots Embedded in Mesostructured Silica Xerogel as High-Performance ECL Emitters: Preparation and Application for MicroRNA-126 Detection.

Unlike the organic micro/nanocrystals prepared using an emerging reprecipitation method, a novel method of embedding 1-pyrenecarboxaldehyde dots (PycDs) into a mesostructured silica xerogel (PycDs@MSX) for use as electrochemiluminescence (ECL) emitters was first proposed to achieve an extremely strong ECL response, with peroxydisulfate (S2O82-) used as a coreactant. In this method, (i) PycDs@MSX could ensure the reversal of the PycDs environment from hydrophobic to hydrophilic and (ii) PycDs@MSX could provide massive porous channels, allowing for access of hydrophilic reactive intermediates (i.e., sulfate anion radicals, SO4•-), which could accelerate the rate of mass transfer and electron transfer between S2O82- and PycDs. Using Ag nanoparticles as a coreaction accelerator and a 3D DNA nanomachine as a signal amplification strategy, the proposed ECL biosensing platform was constructed and achieved ultrasensitive detection of microRNA-126 with an excellent linear range (from 100 aM to 100 pM) and a low detection limit (13.0 aM). More importantly, this work not only developed an innovative avenue to improve the ECL efficiency of organic emitters in aqueous phases but also provided a powerful strategy for biochemical analysis and disease diagnosis applications.

SnS2 Quantum Dots as New Emitters with Strong Electrochemiluminescence for Ultrasensitive Antibody Detection.

Herein, we designed an electrochemiluminescence (ECL) biosensor with SnS2 quantum dots (SnS2 QDs) as novel emitters for the ultrasensitive assay of cytomegalovirus pp65 antibody (anti-CMV pp65) via smart circular peptide-DNA nanomachine amplification. First, the novel ECL biosensing platform was constructed by self-assembly of water-soluble, nontoxic, and earth-abundant SnS2 QDs on the 3D hierarchical silver nanoflowers (Ag NFs) surface, where the Ag NFs, as coreaction accelerator in the ECL ternary (SnS2 QDs/S2O82-/Ag NFs) system, could efficiently boost the ECL intensity of SnS2 QDs. Furthermore, we designed a specific nucleic acid sequence labeled antigenic peptide to act as multifunctionalized capture probe (CP), which could specifically recognize the target antibody assisting with two auxiliary DNA strands via the proximity hybridization of DNA motifs to form a smart circular peptide-DNA nanomachine. Then, with the aid of nuclease, the resultant circular peptide-DNA nanomachine could initiate the subsequent cascade recycling amplification to output massive DNA products as mimic target (MT). As a result, the proposed ECL biosensor for anti-CMV pp65 detection exhibited high sensitivity with a wide linear range from 1 fM to 100 nM and a low detection limit (0.33 fM). Importantly, this work not only first utilized SnS2 QDs as promising ECL emitters for biosensing platform construction but also opened an efficient way for highly sensitive and selective detection of antibody in disease diagnosis and clinical analysis.

Electrochemiluminescence biosensing based on different modes of switching signals.

Electrochemiluminescence (ECL) has attracted much attention in various fields of analysis owing to low background signals, high sensitivity, and excellent controllability. In recent years, to further boost the performance of biosensors, diverse output signal modes have been developed, which exhibited respective advantages. In this review, we summarize the latest sensing applications of ECL bioanalysis by generalizing different output signal modes and give future perspectives for new developments in ECL analytical technology.

Silver Ions as Novel Coreaction Accelerator for Remarkably Enhanced Electrochemiluminescence in a PTCA-S2O82- System and Its Application in an Ultrasensitive Assay for Mercury Ions.

In this work, with the use of Ag(I) ion as robust coreaction accelerator for the enhancement of 3,4,9,10-perylenetetracarboxylic acid-peroxydisulfate (PTCA-S2O82-) system, a highly sensitive solid-state electrochemiluminescence (ECL)-biosensing platform was successfully designed for the detection of mercury ions (Hg2+). Specifically, a long guanine-rich (C-rich) double-stranded DNA (dsDNA) was generated by the target-Hg2+-controlled DNA machine that could amplify the ECL signal of the PTCA-S2O82- system by embedding the Ag(I) ion. Herein, the Ag(I) ion, as a coreaction accelerator, could first react with S2O82- to produce Ag(II) ion and a sulfate radical anion (SO4·-). Then, the accompanying Ag(II) ion could react with H2O to generate the reactive intermediate species (i.e., hydroxyl radical (OH·)), which could further accelerate the reduction of S2O82- to output more SO4·-. Moreover, the recycling of the Ag(I) ion and Ag(II) ion was easily achieved by the electrochemical reaction. Therefore, an avalanche-type reaction was triggered to generate massive amounts of SO4·-, which could react with the luminophore (PTCA) to achieve an extremely strong ECL signal. The ECL mechanism was investigated by ECL and cycle voltammetry (CV) and by the analysis of the fluorescence (FL), ECL, and electron-paramagnetic-resonance (EPR) spectra. As a result, the proposed solid-state ECL-biosensing platform for Hg2+ detection exhibited high sensitivity, with a linear range from 1 × 10-15 to 1 × 10-10 M and a detection limit of 3.3 × 10-16 M. Importantly, this work was the first to utilize a metal ion as a coreaction accelerator and provided a promising approach to improve the sensitivity of target analyses in ECL-biosensing fields.

A robust, magnetic, and self-accelerated electrochemiluminescent nanosensor for ultrasensitive detection of copper ion.

It is well known that the conventional electrochemiluminescence (ECL) biosensor rely on the heterogeneous assay formats that involves the immobilization of biorecognition probe on the electrode surface before signal collection, which inevitably cause the efficiency of bio-recognition reactions to be limited owing to the existence of local steric hindrance. Herein, a robust, magnetic, and self-accelerated ECL nanosensor based on the multifunctionalized cobalt ferrite magnetite nanoparticles (CoFe2O4 MNPs) was firstly designed for copper ion (Cu2+) detection in quasi-homogeneous system. The prepared nanosensor has its unique advantages compared to the iron oxide (Fe3O4) MNPs-based nanosensor for which magnetic nanoparticle just provide the reaction interface and magnetic enrichment. Specifically, the prepared CoFe2O4 MNPs-based biosensing platform could bridge the gap between aqueous phase and solid materials in homogeneous solution, achieving the expansion of reaction area and the reduction of local steric hindrance with high biorecognition efficiency. Furthermore, compared with the common magnetite nanosensors, the prepared CoFe2O4 MNPs achieved a set of magnetic collection, biorecognition probes immobilization, rapid separation and signal amplification in an ECL measurement system because it could act as a new co-reaction accelerator in ECL ternary (PTC-NH2 + S2O82- + CoFe2O4) system, achieving a self-accelerated biosensing platform with significant enhancement of the detection sensitivity. As expected, the prepared CoFe2O4 MNPs-based ECL nanosensors were successfully applied for ultrasensitive detection of Cu2+via click reaction with a linear range from 10-13 M to 1.0 × 10-7 M, which exhibited high sensitivity, excellent selectivity and good reproducibility.

Strong Electrochemiluminescence from MOF Accelerator Enriched Quantum Dots for Enhanced Sensing of Trace cTnI.

The development of a sensitive and practical electrochemiluminescence (ECL) bioassay relies on the use of ECL signal tags whose signal intensity is high and stable. In this work, strong ECL emission was achieved from metal organic framework (MOF) accelerator enriched quantum dots (CdTe), which were applied as an efficient ECL signal tag for trace biomarker detection. It is particularly noteworthy that a novel mechanism to drastically enhance the ECL intensity of CdTe is established because isoreticular metal organic framework-3 (IRMOF-3) with 2-amino terephthalic acid (2-NH2-BDC) as the organic ligand not only allows for loading a large amount of CdTe via the encapsulating effect and internal/external decoration but also functions as a novel coreactant accelerator for promoting the conversion of coreactant S2O82- into the sulfate radical anion (SO4•-), further boosting the ECL emission of CdTe. On the basis of the simple sandwich immunoreaction approach, cardiac troponin-I antigen (cTnI), a kind of biomarker related with myocardial infarction, was chosen as a detection model using an IRMOF-3-enriched CdTe labeled antibody as the signal probe. This immunosensor demonstrated desirable assay performance for cTnI with a wide response range from 1.1 fg mL-1 to 11 ng mL-1 and a very low detection limit (0.46 fg mL-1). This suggested that the IRMOF-3-enriched CdTe nanocomposite strategy can integrate the coreactant accelerator and luminophore to significantly enhance the ECL intensity and stability, providing a direction for promising ECL tag preparation with broad applications.

Hemin as electrochemically regenerable co-reaction accelerator for construction of an ultrasensitive PTCA-based electrochemiluminescent aptasensor.

In this work, hemin was firstly used as electrochemically regenerable co-reaction accelerator for signal amplification to develop an ultrasensitive aptasensor for Aflatoxin M1 (AFM1) detection. Initially, the perylenetetracarboxylic acid (PTCA) was directly employed as luminophore to construct the ECL sensing nano-platform by combining Au nanoparticles (Au NPs) for immobilizing thiol-terminated hairpin probe (H1). Then with the help of hairpin H2, H3, the AFM1-catalyzed hairpin assembly (CHA) was executed to produce the H1-H3 duplex, which could further initiate the hybridization chain reaction (HCR) to generate dendritic DNA polymers consisting of G-rich sequence for capturing large quantities of hemin on the electrode surface. Herein, hemin as electrochemically regenerable co-reaction accelerator could interact with the co-reactant (S2O82-) to obviously improve the luminous efficiency of the PTCA. Therefore, a strong and stable ECL signal was achieved by the employment of hemin as electrochemically regenerable co-reaction accelerator. The proposed aptasensor determined AFM1 down to 0.09pgmL-1 within a linear range of 0.4pgmL-1 to 400ngmL-1. With excellent sensitivity and stability, the strategy provided an efficient and simple method for the trace detection of biomolecules in clinical analysis.

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 H2O2 as co-reactant was demonstrated and the possible ECL mechanism was proposed. Furthermore, a significantly amplified ECL response could be obtained via Ag and Fe-Fe2O3 nanoparticles as bis-co-reaction accelerator. As a result, the proposed ECL immunosensor performed good sensitivity and accuracy with a detection limit down to 0.03pg/mL. Moreover, this immunosensor was successfully employed to monitor patient serum, which exhibited an alternative avenue for the early diagnosis of other diseases via proteins, nucleotide sequence, microRNA and cells.

Novel electrochemiluminescence of perylene derivative and its application to mercury ion detection based on a dual amplification strategy.

In this paper, a novel covalently crosslinked perylene derivative (PTC-PEI) composed of polyethylenimine (PEI) and perylenetetracarboxylic acid (PTCA) has been first investigated for cathodic electrochemiluminescence (ECL) in an aqueous system with dissolved O2 as coreactant. The promising novel ECL materials of PTC-PEI exhibited admirable physical and chemical stability and high ECL intensity, which held an alternative way to construct ECL sensor with improved sensitivity. Thus, it was applied to construct a dual amplified "signal-on" mercury ion (Hg(2+)) sensor by the employment of nicking endonuclease (NEase)-assisted target recycling and rolling circle amplification (RCA) for signal amplification. Herein, a long G-rich sequence was generated by RCA process to capture abundant hemin on the electrode surface, and then a significantly amplified ECL signal of PTC-PEI was obtained. Based on dual signal amplification strategy, the devised sensor showed a linear range from 0.1pM to 0.1µΜ with a detection limit down to 33fM (S/N=3), and was successfully used in the direct detection of real water sample with high sensitivity and selectivity.

Electrochemiluminescence of Supramolecular Nanorods and Their Application in the "On-Off-On" Detection of Copper Ions.

In this work, an "on-off-on" switch system has been successfully applied through the construction of an electrochemiluminscent biosensor for copper ion (Cu(2+) ) detection based on a new electrochemiluminescence (ECL) emitter of supramolecular nanorods, which was achieved through supramolecular interactions between 3,4,9,10-perylenetetracarboxylic acid (PTCA) and aniline. The initial "signal-on" state with strong and stable ECL emission was obtained by use of the supramolecular nanorods with a new signal amplification strategy involving a co-reaction accelerator. In addition, ECL quencher probes (Fc-NH2 /Cu-Sub/nano-Au) were fabricated by immobilizing aminoferrocene (Fc-NH2 ) on Cu-substrate strand modified Au nanoparticles. The quencher probes were hybridized with the immobilized Cu-enzyme strand to form Cu(2+) -specific DNAzyme. Similarly, the "signal-off" state was obtained by the high quenching effect of Fc-NH2 on the ECL of the excited-state PTCA ((1) PTCA*). As expected, the second "switch-on" state could achieved by incubating with the target Cu(2+) , owing to the Cu(2+) -specific DNAzyme, which was irreversibly cleaved, resulting in the release of the quencher probes from the sensor interface. Herein, on the basis of the ECL intensity changes (ΔIECL ) before and after incubating with the target Cu(2+) , the prepared Cu(2+) -specific DNAzyme-based biosensor was used for the determination of Cu(2+) concentrations with high sensitivity, excellent selectivity, and good regeneration.

Electrochemiluminescence Resonance Energy Transfer System: Mechanism and Application in Ratiometric Aptasensor for Lead Ion.

In this paper, a novel electrochemiluminescence resonance energy transfer (ECL-RET) system from O2/S2O8(2-) to a kind of amino-terminated perylene derivative (PTC-NH2) was demonstrated for the first time, which was then applied to construct a ratiometric aptasensor for lead ion (Pb(2+)) detection. First, gold-nanoparticles-functionalized fullerene nanocomposites (AuNPs@nano-C60) were coated on a glassy carbon electrode (GCE), and then thiol-modified assistant probes (APs) were attached on AuNPs@nano-C60/GCE. Then the resultant electrode was hybridized with capture probes (the aptamer of the Pb(2+), abbreviated as CPs) to generate DNA duplexes, which could induce PTC-NH2 to be intercalated into the dsDNA grooves by the electrostatic adsorption. Herein, ECL dual peaks at -0.7 V (vs Ag/AgCl) and -2.0 V (vs Ag/AgCl) were obtained when the prepared aptasensor was detected in air-saturated S2O8(2-) solution, which could be attributed to the emission of excited dimmers (π-excimers) ((1)(NH2-PTC)2*) and (1)(O2)2*, respectively. In the presence of Pb(2+), the dsDNA was unwound, and Pb(2+) G-quadruplex structure was generated because of the highly specific affinity between Pb(2+) and CPs, which made the PTC-NH2 release from the electrode surface. As a result, the ECL signal at -0.7 V was decreased, and the ECL signal around -2.0 V was increased. By measuring the ratio of ECL intensities at two excitation potentials, the developed aptasensor exhibited the linear response range from 1.0 × 10(-12) M to 1.0 × 10(-7) M with a detection limit of 3.5 × 10(-13) M (S/N = 3) for Pb(2+), which could offer an alternative analytical method with excellent properties of high selectivity, accuracy, and sensitivity.

Mannose-binding lectin inhibits monocyte proliferation through transforming growth factor-ß1 and p38 signaling pathways.

Mannose-binding lectin (MBL), a plasma C-type lectin, plays an important role in innate immunity. However, the interaction, and the consequences of it, between MBL and the immune system remain ill defined. We have investigated the contributing mechanisms and effects of MBL on the proliferation of human monocytes. At lower concentrations (≤4 µg/ml) MBL was shown to partially enhance monocyte proliferation. By contrast, at higher concentrations (8-20 µg/ml) of MBL, cell proliferation was markedly attenuated. MBL-induced growth inhibition was associated with G0/G1 arrest, down-regulation of cyclin D1/D3, cyclin-dependent kinase (Cdk) 2/Cdk4 and up-regulation of the Cdk inhibitory protein Cip1/p21. Additionally, MBL induced apoptosis, and did so through caspase-3 activation and poly ADP-ribose polymerase (PARP) cleavage. Moreover, transforming growth factor (TGF)-ß1 levels increased in the supernatants of MBL-stimulated monocyte cultures. We also found that MBL-dependent inhibition of monocyte proliferation could be reversed by the TGF-ß receptor antagonist SB-431542, or by anti-TGF-ß1 antibody, or by the mitogen-activated protein kinase (MAPK) inhibitors specific for p38 (SB203580), but not ERK (U0126) or JNK (SP600125). Thus, at high concentrations, MBL can affect the immune system by inhibiting monocyte proliferation, which suggests that MBL may exhibit anti-inflammatory effects.