Strong aggregation-induced electrochemiluminescence of pyrene-coordination metal-organic frameworks coupled with zero-valent iron as novel accelerator for ultrasensitive immunoassay.

Polycyclic aromatic hydrocarbons (PAHs) are excellent alternative luminophores for electrochemiluminescence (ECL) immunoassays. However, they are inevitably limited by the aggregation-caused quenching effect. In this study, aimed at eliminating the aggregation quenching of PAHs, luminescent metal-organic frameworks (MOFs) with 1,3,6,8-tetra(4-carboxybenzene)pyrene (H4TBAPy) as the ligand were exploited as a novel nano-emitter for the construction of ECL immunoassays. The luminophore exhibits efficient aggregation-induced emission enhancement, good acid-base resistance property and unusual ECL reactivity. In addition, the simultaneous use of potassium persulfate and hydrogen peroxide as dual co-reactants resulted in a synergistic enhancement of the cathodic ECL efficiency. The use of magnetic iron-nickel alloys as the multifunctional sensing platform can further enhance the ECL activity, and its enriched zero-valent iron as a co-reactant accelerator effectively drives ECL analytical performance. Profiting from the excellent characteristics, signal-on ECL immunoassays have been constructed. With carcinoembryonic antigen as the model analysis target, a detection limit of 0.63 pg/mL was obtained within the linear range of 1 pg/mL to 50 ng/mL, accompanied by excellent analytical performance. This report opens a new window for the rational design of efficient ECL illuminators, and the proposed ECL immunoassays may find promising applications in the detection of disease markers.

Dual-mode self-powered photoelectrochemical and colorimetric determination of procalcitonin accomplished by multienzyme-expressed Ni4Cu2 bimetallic hollow nanospheres and spherical nanoflower-MoS2/Cu2ZnSnS4/Bi2S3.

Bacterial infections, viral infections and autoimmune diseases pose a considerable threat to human health. Procalcitonin (PCT) has emerged as a biomarker for the detection of these diseases. To ensure accurate and reliable results, we propose a dual-mode approach that incorporates self-validation and self-correction mechanisms. Herein, we develop a dual-mode self-powered photoelectrochemical (PEC) and colorimetric sensor to determine PCT. The self-powered PEC sensor was constructed with a photoanode of spherical nanoflower-MoS2/Cu2ZnSnS4/Bi2S3 material and a photocathode of CuInS2 material. Ni4Cu2 bimetallic hollow nanospheres (BHNs) possess superoxide dismutase and catalase performance, which facilitate superoxide anion radical (·O2-) and H2O2 circulating generation, promoting the separation of photogenerated electrons and holes to amplify photocurrent signal. Thus Ni4Cu2 BHNs is used as a marker material for PEC sensor. Meanwhile, in colorimetric mode, Ni4Cu2 BHNs converts blue oxTMB to a colourless TMB for colorimetric detection of PCT. Based on this principle, dual-mode determination of PCT with high sensitivity is achieved. The dual-mode method not only demonstrates outstanding properties and practicability, but also presents an effective, highly efficient and reliable method for detecting PCT.

Antioxidant Cascade Modulated Electrochemiluminescence by a Biomimetic Metal-Organic Framework with Dual Enzymatic Activity for Disease Marker Immunoassays.

High-performance electrochemiluminescence is a significant approach for the examination of disease biomarkers, and the utilization of innovative electrochemiluminescence detection systems represents a viable strategy to enhance the efficacy of ECL analysis. In this work, the biomimetic engineering metal-organic framework (MOF-818) has realized the ultrasensitive ECL immunoassay of disease markers based on the guidance of the free radical scavenging strategy provided by the antioxidant cascade. Initially, we synthesized a hydrogen-bonded organic framework (HOF) consisting of luminol and three active ligands based on simple room-temperature self-assembly. The luminol-HOF (L-HOF) showed more stable and brighter ECL luminescence activity than the monomer due to the nano-confinement enhancement of the coordinated luminol units. Subsequently, MOF-818 with biomimetic superoxide dismutase (SOD) and catalase (CAT) activities were recruited for the first time as quenching agents for sandwich immunoassay mode. The enzyme activity leads to the reverse transformation of superoxide anion radicals (O2-) and further antioxidant decomposition, decreasing in the responsiveness of luminol ECL signals. Using carcinoembryonic antigen (CEA) as an analytical model, a detection limit of 0.457 pg/mL was obtained within a detection range of 0.001-50 ng/mL. We believe that this novel sandwich sensing model based on enzyme activity provides a meaningful potential tool for precise detection, expanding the broader application of nanoenzymes in analysis.

Co-amplification of luminol-based electrochemiluminescence immunosensors based on multiple enzyme catalysis of bimetallic oxides CoCeOx and NiMnO3 for the detection of CYFRA21-1.

The accelerated energy supply of co-reactants is an extremely effective strategy for achieving highly sensitive electrochemiluminescence analysis, and binary metal oxides would be an excellent tool for this purpose owing to the nano-enzyme acceleration of mixed metal valence states. Herein, an electrochemiluminescent (ECL) immunosensor for monitoring the concentration of cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) was developed based on a co-amplification strategy triggered by two bimetallic oxides, CoCeOx and NiMnO3, with luminol as the luminophore. CoCeOx derived from an MOF exhibits a large specific surface area and excellent loading capacity as a sensing substrate, and the peroxidase properties enable the catalysis of hydrogen peroxide to provide energy supply to the underlying radicals. The dual enzymatic properties of flower-like NiMnO3 were employed as probe carriers for luminol enrichment. The peroxidase properties built on Ni2+/Ni3+ and Mn3+/Mn4+ binary redox pairs resulted in the integration of highly oxidative hydroxyl radicals, and the oxidase properties provided additional superoxide radicals via dissolved oxygen. The practically proven multi-enzyme-catalyzed sandwich-type ECL sensor easily accomplished an accurate immunoassay of CYFRA21-1, harvesting a detection limit of 0.3 pg mL-1 in the linear range of 0.001-150 ng mL-1. In conclusion, this work explores the cyclic catalytic amplification of mixed-valence binary metal oxides with nano-enzyme activity in the field of ECL and develops an effective pathway for ECL immunoassay.

High-Performance Electrochemiluminescence of a Coordination-Driven J-Aggregate K-PTC MOF Regulated by Metal-Phenolic Nanoparticles for Biomarker Analysis.

The elimination of aggregation-caused quenching of polycyclic aromatic hydrocarbons by metal-ligand coordination is of immense scientific interest in solid-state electrochemiluminescence (ECL) sensing. Herein potassium ion (K+)-mediated J-aggregate K-PTC MOF (PTCA, perylene-3,4,9,10-tetracarboxylic) was synthesized and employed to formulate an ECL immunosensor for biomarker detection. The coordination-driven aggregates are arranged in an end-to-end side mode, which overcomes the aggregation-caused quenching related to PTCA concentration. Compared with PTCA, K-PTC MOF shows a more stable ECL emission with an unprecedented red shift to 718 nm and is equipped with ECL activity for analytical applications at a voltage of -1.1 V. Considering the requirements of accurate detection, metal-phenolic bioactive nanoparticles (MPNPs) were synthesized for the construction of a sandwich sensing platform to realize the steady-state regulation of ECL. As proof of applicability, a constructive experiment was carried out with neuron-specific enolase (NSE), a marker of small cell lung cancer (SCLC), as a targeted analyte. With optimal requirements, the configuration can provide a detection range of 10 pg/mL to 50 ng/mL and a detection limit of 7.4 pg/mL, accompanied by sufficient practical analytical performance. Collectively, this paradigm provides a deeper understanding of the ECL characteristics of coordination-driven J-aggregation and provides more possibilities for the development of ECL patterns based on luminescent metal-organic frameworks.

Oxygen Free Radical Scavenger PtPd@PDA as a Dual-Mode Quencher of Electrochemiluminescence Immunosensor for the Detection of AFB1.

Here, a dual-mode quenched electrochemiluminescence (ECL) immunosensor based on PtPd@PDA was proposed. Among them, nitrogen-doped hydrazide conjugated carbon dots (NHCDs), as an ECL emitter and a donor of resonance energy transfer, were quenched by PtPd@PDA (receptor). At the same time, PDA in PtPd@PDA, as an oxygen radical scavenger, completed the further quenching of the ECL signal by consuming O2•- generated by the decomposition of co-reactant H2O2. The dual-mode quenching from the above two channels was achieved. In addition, compared with the traditional carbon quantum dots, NHCDs as ECL emitters had lower excitation potential. Moreover, a large number of amino groups provided by aminated MWCNTs could capture more antibodies while connecting with NHCDs. Under the optimum experimental conditions, taking aflatoxin B1 as the target, the proposed sensor with good specificity, stability, and reproducibility had good linearity when the concentration of AFB1 was 0.01-100 ng/mL, with the detection limit of 2.63 pg/mL (S/N = 3). This strategy provided more possibilities for the application of dopamine metal nanocomposites in electrochemiluminescence analysis and offered a new approach to detect AFB1.

CePO4/CeO2 heterostructure and enzymatic action of D-Fe2O3 co-amplify luminol-based electrochemiluminescence immunosensor for NSE detection.

The construction of advanced systems that can accurately detect neuron-specific enolase (NSE) is critical to the rapid diagnosis of small cell lung cancer (SCLC). Herein, a luminol-based electrochemiluminescence (ECL) biosensor enhanced by reactive oxygen species (ROS) is proposed to perform the ultrasensitive detection of NSE. D-Fe2O3@Pt, synthesized as a signal indicator, was combined with luminol to significantly shorten its electron transfer pathway. Its peroxidase activity catalyzed the decomposition of H2O2 to generate a large amount of •OH, thus considerably increasing the ECL signal of the luminol-H2O2 system. CePO4/CeO2 heterostructures with improved surface-active areas were then employed as sensing substrates. The platform enabled the accelerated generation of O2•- through enriched Ce4+/Ce3+ redox pairs, thereby amplifying the strength of the response of the foundation. Through integrated dual ROS amplification, the proposed sandwich ECL immunosensor configuration achieved sensitive detection in the detection range of 76 fg/mL - 100 ng/mL, with a detection limit of 72.4 fg/mL. Furthermore, the sensor exhibited high selectivity for the determination of NSE in human serum. Overall, this study serves as an important reference for integrating ROS and enzymatic strategies in ECL research to achieve accurate, sensitive, and highly selective detection of a target.

Ratiometric Electrochemical Immunosensor Based on L-cysteine Grafted Ferrocene for Detection of Neuron Specific Enolase.

In order to realize the ultra sensitive detection of Neuron specific enolase (NSE) in human serum, we chose electrochemical immunosensor as a simple analytical method. During the experiment, we found that the peak value signals of Cu-MOFs-Au and Fc-L-Cys were significantly changed at -0.20 V and 0.20 V potentials by DPV. So a ratiometric electrochemical immunosensor for quantitative analysis of NSE was prepared for Cu-MOFs-Au as the electrode sensing surface and Fc-L-Cys as the label of Ab2. The data and performances of the immunosensor were tested and analyzed by DPV. Cu-MOFs not only provide the required signal for the immunosensor, but also have a large specific surface area, which can provide more sites for the placement of Au nanoparticles. L-cysteine (L-Cys) can prevent a large amount of Fc-COOH leakage, so that Fc+ can stably provide another required signal. With the beefing up of NSE concentration, redox peak of Cu-MOFs-Au decreased and that of Fc-L-Cys raised. The ratio (ΔI=ΔICu/ΔIFc) of two different signals was linear with the logarithm of NSE concentration in a certain value range. In brief, with the optimized experimental conditions, the immunosensor showed excellent performance in the concentration range of 1 pg/mL to 1 µg/mL, and the detection limit was 0.011 pg/mL. Compared with other immunosensors, it showed an unexpected high sensitivity. This method also provided a new idea for the ultra sensitive quantitative detection of other biomarkers.

CSE-Derived H2S Inhibits Reactive Astrocytes Proliferation and Promotes Neural Functional Recovery after Cerebral Ischemia/Reperfusion Injury in Mice Via Inhibition of RhoA/ROCK2 Pathway.

The effect of cystathionine-γ-lyase (CSE)-derived hydrogen sulfide (H2S) on the reactive proliferation of astrocytes and neural functional recovery over 30 d after acute cerebral ischemia and reperfusion (I/R) was determined by applying wild-type (WT) and CSE knockout (KO) mice. The changes of glial fibrillary acidic protein (GFAP) expression in hippocampal tissues was tested. Besides, we assessed the changes of mice spatial learning memory ability, neuronal damage, RhoA, Rho kinase 2 (ROCK2), and myelin basic protein (MBP) expressions in hippocampal tissues. The results revealed that cerebral I/R resulted in obvious increase of GFAP expression in hippocampal tissues. Besides, we found the neuronal damage, learning, and memory deficits of mice induced by cerebral I/R as well as revealed the upregulation of RhoA and ROCK2 expressions and reduced MBP expression in hipppcampal tissues of mice following cerebral I/R. Not surprisingly, the GFAP expression and cerebral injury as well as the upregulation of the RhoA/ROCK2 pathway were more remarkable in CSE KO mice, compared with those in WT mice over 30 d following acute cerebral I/R, which could be blocked by NaHS treatment, a donor of exogenous H2S. In addition, the ROCK inhibitor Fasudil also inhibited the reactive proliferation of astrocytes and ameliorated the recovery of neuronal function over 30 d after cerebral I/R. For the purpose of further confirmation of the role of H2S on the astrocytes proliferation following cerebral I/R, the immunofluorescence double staining: bromodeoxyuridine (BrdU) and GFAP was evaluated. There was a marked upregulation of BrdU-labeled cells coexpressed with GFAP in hippocampal tissues at 30 d after acute cerebral I/R; however, the increment of astrocytes proliferation could be ameliorated by both NaHS and Fasudil. These findings indicated that CSE-derived H2S could inhibit the reactive proliferation of astrocytes and promote the recovery of mice neural functional deficits induced by a cerebral I/R injury via inhibition of the RhoA/ROCK2 signal pathway.

Ratiometric electrochemical immunosensor for the detection of procalcitonin based on the ratios of SiO2-Fc-COOH-Au and UiO-66-TB complexes.

Procalcitonin (PCT) as a disease marker is of great significance in the early diagnosis of septicemia and pyemia. Biosensor have good prospects for analysis and detection of disease markers, but developing highly sensitive detection methods for detecting PCT remains a daunting task. In this paper, we develop a ratiometric electrochemical immunosensor with Au NPs modified SiO2-Fc-COOH complex as matrix and UiO-66 loaded with Toluidine blue (TB) as a marker for quantitative detection of procalcitonin (PCT). The SiO2 modified by APTES not only has a large specific surface area but also contains abundant amino groups, which can be connected to the electrochemical probe of ferrocenecarboxylic acid (Fc-COOH). UiO-66 has the advantages of large specific surface area, high porosity and adjustable structure, which can adsorb toluidine blue electrochemical probe through electrostatic attraction. Measurement and analysis of the prepared immunosensor by Differential Pulse Voltammetry (DPV) show that the oxidation peak currents of Fc-COOH and TB appear at potentials of 0.30 V and -0.30 V respectively. As the PCT concentration increases, the oxidation peak current of TB increases and the oxidation peak current of Fc-COOH decreases. The ratios (ΔI=ΔITB/ΔIFc-COOH) between the double signals could show a certain linear relationship with the concentration of the PCT within a certain range. Under optimal conditions, the linear range of detection obtained by the immunosensor was 1 pg/mL-100 ng/mL and the detection limit was 0.3 pg/mL. In this work, the developed ratiometric electrochemical immunosensor not only provides a simple, reliable and sensitive strategy for quantitative detection of PCT but also provides a useful method for clinical detection of other disease markers.

Recognition of M2 type tumor-associated macrophages with ultrasensitive and biocompatible photoelectrochemical cytosensor based on Ce doped SnO2/SnS2 nano heterostructure.

Tumor-associated macrophages (TAMs) play central roles in the regulation of tumor growth. TAMs can be differentiated into M1 and M2 types, which are responsible for the inhibition and growth of tumor tissues, respectively. Recognition of M2-TAMs is significant for the diagnosis and therapy of cancer, which is however severely limited due to the deficiency of selective and sensitive photoelectrochemical sensors. In this work, using Ce doped SnO2/SnS2 nano heterostructure as the highly sensitive platform, a photoelectrochemical sensor enabling the recognition of M2-TAMs was fabricated for the first time. By the decoration of CD163 antibody on the platform, the ultrasensitive photoelectrochemical sensor can selectively detect the CD163 protein on the surface of M2-TAMs. To our best knowledge, this is the first demonstration for recognition of M2-TAMs using photoelectrochemical method. The fabricated cytosensor has ultra-sensitive photocurrent response, applicable biological compatibility, high selectivity and relatively wide linear sensing range (5 × 101 to 1 × 105 cells/ml) with a low detection limit (50 cells/ml) for the detection of M2-TAMS. This kind of PEC cytosensor would provide a novel analysis and detection strategy for M2-TAMs.

Electrochemiluminescence immunosensor of "signal-off" for ß-amyloid detection based on dual metal-organic frameworks.

In this work, a "signal-off" sandwich electrochemiluminescence (ECL) immunosensor was fabricated for ingenious detection of Alzheimer's disease marker ß-amyloid (Aß) based on dual metal-organic frameworks (dual-MOFs), which included NH2-UiO-66 and MIL-101. Dual-MOFs with high porosity and plentiful functional groups can increase the biomolecules binding rate, and through the synergy with the different materials can effectively amplify the inherent properties of the material itself. Ru(bpy)32+ was capsulated in NH2-UiO-66 as luminophor, the complex possessed steady and excellent luminescence efficiency as well as large specific surface area to load sufficient antibodies. MoS2 quantum dots (MoS2 QDs) combined with MIL-101 via Au-S bond. MIL-101@Au-MoS2 QDs was used for the label of secondary antibodies (Ab2) to quench the ECL signal of Ru(bpy)32+/NH2-UiO-66. The amount of Ab2-MIL-101@Au-MoS2 QDs bound to antigen will gradually accrue with the increase of the concentration of Aß, which led to "signal-off" for accurate estimation of Aß. Under optimal conditions, the developed assay for Aß detection demonstrated a wide linear range of 10-5 ng mL-1 to 50 ng mL-1 and the detection limit was as low as 3.32 fg mL-1 (S/N = 3). The cooperation of dual-MOFs has potential as a universal strategy for quantitative analysis of other targets.

Electrochemiluminescence immunoassay for the N-terminal pro-B-type natriuretic peptide based on resonance energy transfer between a self-enhanced luminophore composed of silver nanocubes on gold nanoparticles and a metal-organic framework of type MIL-125.

The N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a marker of heart failure. A novel sandwich type electrochemiluminescence (ECL) immunoassay is described for the NT-proBNP. The method is based on ECL resonance energy transfer (RET) between silver nanocubes that were covered with semicarbazide-modified gold nanoparticles (AgNC-sem@AuNPs) as the donor, and a Ti(IV)-based metal-organic framework of type MIL-125 as the acceptor. The ECL signal was strongly amplified by increasing the luminous efficiency. ECL-RET occurs due to the partial overlap between the ECL emission of the AgNC-sem@AuNPs (emission wavelength at 470 nm to 900 nm) and the visible absorption spectrum of MIL-125 (absorption wavelength at 406 nm to 900 nm). This results in the quenching of ECL. The AgNC-sem@AuNPs were placed on the electrode. The antibody was immobilized on AgNC-sem@AuNPs via Au-NH2 bond, and MIL-125 was utilized as a label for the secondary antibody. The assay works in the 0.25 pg mL-1 to 100 ng mL-1 concentration range and has a 0.11 pg mL-1 lower detection limit (at S/N = 3). Graphical abstract Schematic representation of self-enhanced luminescence mechanism (semicarbazide (Sem) as co-reaction accelerator) and Electrochemiluminescence resonance energy transfer (ECL-RET): silver nanocubes (AgNCs) as the energy donor and MIL-125 as the energy acceptor.

Dual-signal sandwich electrochemical immunosensor for amyloid ß-protein detection based on Cu-Al2O3-g-C3N4-Pd and UiO-66@PANI-MB.

Combining of amperometric and square wave voltammetric methods (SWV), the dual-signal sandwich electrochemical immunosensor was developed for quantitative determination of amyloid ß-protein (Aß). Cu was doped into Al2O3 lattice (Cu-Al2O3) and reacts with graphite carbon nitride (g-C3N4) to generate Cu-Al2O3-g-C3N4 with internal dual-reaction center structure, which has good catalytic properties of hydrogen peroxide (H2O2). Subsequently, palladium nanoparticles (Pd NPs) was introduced into Cu-Al2O3-g-C3N4 (Cu-Al2O3-g-C3N4-Pd) that not only synergistically catalyzed H2O2 but also immobilized anti-Aß (Ab1) via Pd-NH2. The Cu-Al2O3-g-C3N4-Pd was used as matrix material to modify the electrode, which can produce obviously electrochemical signals through Amperometry i-t curve. Meanwhile, the Zr6O4(OH)4(CO2)12 (UiO-66) modified with polyaniline (PANI) has the large specific surface, good conductivity and adsorption capacity, which can support methylene blue (MB) as signal label of anti-Aß (Ab2). Therefore, the UiO-66@PANI-MB can provide an obviously electrochemical signal about MB through SWV. Under optimal conditions, the dual-signal sandwich electrochemical immunosensor has salient analytical performance and both signal platforms provide more accurate results. The linear range of detection obtained by the immunosensor was 10 fg/mL-100 ng/mL, and the detection limit was 3.3 fg/mL. This method not only provided a reliable guarantee for the experimental detection but also provided an effective strategy for the detection of other biological.

Ultrasensitive electrochemiluminescence immunosensor for the detection of amyloid-ß proteins based on resonance energy transfer between g-C3N4 and Pd NPs coated NH2-MIL-53.

An electrochemiluminescence (ECL) analytical platform was proposed for ultrasensitive detection of amyloid-ß proteins (Aß) based on the ECL resonance energy transfer (ECL-RET). In this work, gold nanoparticles-functionalized graphitic carbon nitride nanosheets (g-C3N4@Au NPs) and palladium nanoparticles-coated Metal organic framework (Pd NPs@NH2-MIL-53) were synthesized, which were as ECL donor and ECL acceptor respectively. A strong cathode ECL emission was obtained from the g-C3N4@Au NPs when used K2S2O8 as its co-reactant. Here, Au NPs not only was used as an accelerator to enhance and stabilize the ECL signal, but also a connector for attaching Aß antibody. In addition, NH2-MIL-53(Al) was selected as a label material for supporting Pd NPs to synergistically increase the intensity and range of UV-visible absorption. The ECL signal of g-C3N4@Au NPs was intensely decreased when the ECL acceptor probe Pd NPs@NH2-MIL-53 was incubated onto the modified GCE by way of the specific recognition. Under the optimal condition, a wide detection range from 10 fg/mL to 50  ng/mL and a low detection limit of 3.4 fg/mL (S/N = 3) were obtained. In consideration of favorable specificity, stability and reproducibility, the proposed method was successfully applied for Aß detection in actual human serum samples and could be a potential analytical tool for sensitive molecular trace detection in clinical analysis.

Construction of the FRET Pairs for the Visualization of Mitochondria Membrane Potential in Dual Emission Colors.

Mitochondria membrane potential (MMP) play significant roles during metabolism, signaling, and other important bioevents. Visualization of MMP levels is essential for many biological researches. However, fluorescent probes for monitoring MMP levels in dual emission colors are still deficient, which greatly limited the development of relative research areas. In this work, a pair of fluorescent probes have been designed and synthesized to monitor the MMP levels in dual emission colors based on Forster resonance energy transfer (FRET) mechanism. The FRET donor (FixD) is constructed by linking a benzyl chloride group to a fluorophore with bright-green emission. The FixD could target mitochondria and be immobilized in mitochondria by linking to the thiol group of mitochondrial proteins. The FRET acceptor (LA) is designed with green absorption and deep-red emission. In live cells with high MMP levels, FixD and LA both target mitochondria, and deep-red (DR) emission could be detected with the excitation of 405 nm. Particularly, the spectral shift of fluorescence upon the decrease of MMP is up to 110 nm, which is greatly favorable for the clear observation of MMP levels. With the decrease of MMP, LA would be released from mitochondria while FixD would still be immobilized in mitochondria, and decreased DR emission and increased green fluorescence could be detected due to the absence of FRET. In this manner, the MMP levels could be monitored in dual emission colors.

Dual mode competitive electrochemical immunoassay for B-type natriuretic peptide based on GS/SnO2/polyaniline-Au and ZnCo2O4/N-CNTs.

A sensitive dual mode competitive electrochemical immunosensor for the detection of B-type natriuretic peptide (BNP) was successfully fabricated, which based on differential pulse voltammetry (DPV) and amperometric i-t curve response modes. Polyaniline (PAN) and tin dioxide (SnO2) were loaded on graphene sheets (GS), which could effectively promote the electron transfer process, thereby amplifying the current signal and increasing the sensitivity of the immunosensor. To promote biocompatibility, gold nanoparticles (Au) were incorporated on GS/SnO2/PAN (GS/SnO2/PAN-Au). GS/SnO2/PAN-Au complex was gotten to act as the platform which could provide a clearly DPV signals. N-doped carbon nanotubes (N-CNTs) embellished by ZnCo2O4 quantum dots (ZnCo2O4/N-CNTs) with excellent catalytic properties for the reduction of H2O2 was gotten to act as the label of the antibody-BNP (Ab), providing an obviously current signal through amperometric i-t curve method. A large quantity of BNP could be stable loaded in the modified electrode via GS/SnO2/PAN-Au with excellent electrical conductivity and good biocompatibility, which could compete with target-BNP to combine Ab that labelled by ZnCo2O4/N-CNTs. Under the optimum conditions, the immunosensor exhibited remarkable analytical performance of a linear range from 0.01 pg/mL to 1 ng/mL with a detection limit of 3.4 fg/mL for quantitative detection of BNP (S/N = 3). This method was able to become a universal strategy for other biological detection.

PathRings: a web-based tool for exploration of ortholog and expression data in biological pathways.

BACKGROUND: High-throughput methods are generating biological data on a vast scale. In many instances, genomic, transcriptomic, and proteomic data must be interpreted in the context of signaling and metabolic pathways to yield testable hypotheses. Since humans can interpret visual information rapidly, a means for interactive visual exploration that lets biologists interpret such data in a comprehensive and exploratory manner would be invaluable. However, humans have limited memory capacity. Current visualization tools have limited viewing and manipulation capabilities to address complex data analysis problems, and visual exploratory tools are needed to reduce the high mental workload imposed on biologists. RESULTS: We present PathRings, a new interactive web-based, scalable biological pathway visualization tool for biologists to explore and interpret biological pathways. PathRings integrates metabolic and signaling pathways from Reactome in a single compound graph visualization, and uses color to highlight genes and pathways affected by input data. Pathways are available for multiple species and analysis of user-defined species or input is also possible. PathRings permits an overview of the impact of gene expression data on all pathways to facilitate visual pattern finding. Detailed pathways information can be opened in new visualizations while maintaining the overview, that form a visual exploration provenance. A dynamic multi-view bubbles interface is designed to support biologists' analytical tasks by letting users construct incremental views that further reflect biologists' analytical process. This approach decomposes complex tasks into simpler ones and automates multi-view management. CONCLUSIONS: PathRings has been designed to accommodate interactive visual analysis of experimental data in the context of pathways defined by Reactome. Our new approach to interface design can effectively support comparative tasks over substantially larger collection than existing tools. The dynamic interaction among multi-view dataset visualization improves the data exploration. PathRings is available free at http://raven.anr.udel.edu/~sunliang/PathRings and the source code is hosted on Github: https://github.com/ivcl/PathRings .