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[Display omitted] • Ultrasensitive detection is of great significance for the study of ancient leather artifacts. • A specific anti-collagen polyclonal antibody was well designed and prepared. • An electrochemical immunosensor was developed for detecting ancient leather. • The sensor excels in both qualitative and quantitative analysis. • The sensor has excellent specificity, sensitivity and stability. As one of the earliest and wieldiest used natural materials, leather played a significant role in the development of human civilization. However, as the main component of the leather protein is very susceptible to degradation by light, heat, microorganism and other adverse factors, leather relics are difficult to preserve. To trace leather remnants in ancient sites, a specific anti-collagen polyclonal antibody was designed and prepared through animal immunization. Then, a label-free electrochemical immunosensor based on tailored polyclonal antibody and cobalt hydroxide oxide nanoflakes (CoOOH NFs) was constructed and applied for the detection of leather artifacts in ancient sites. The limit of detection (LOD) of this electrochemical immunosensor reached as low as 0.2858 ng/mL, with a linear range of 1–100 ng/mL. The immunosensor exhibits excellent performance in terms of specificity, stability, and repeatability, especially in the qualitative and quantitative detection of ancient leather samples unearthed from six sites in Xinjiang region, which also enabled the identification of the species of leather artifacts. The present work provides a novel strategy for the trace identification of ancient leather and a reference for the determination of other ancient proteins in ancient sites. [ABSTRACT FROM AUTHOR]

Ultrasensitive detection is crucial for the early warning and intervention of risk factors, ultimately benefiting the environment and human health. Low levels of ochratoxin A (OTA) present a hidden yet significant threat, and rapid detection via high-performing biosensors is therefore essential. A cascade isothermal amplification aptasensor (CIA-aptasensor) was designed for OTA detection. On the surface of a magnetic bead probe, the OTA level was converted into positively correlated trigger cDNA through its competitive binding with OTA-Apt. The released trigger cDNA activated catalytic hairpin assembly followed by coupling with a hybridization chain reaction to achieve CIA. After adding graphene oxide and SYBR Green I, the background interference was eliminated to specifically obtain OTA-related fluorescence. The ultrasensitive limit of detection was 0.22 pg mL−1, an improvement of 1368-fold over conventional enzyme-linked aptamer sorbent assay by the same OTA-Apt, demonstrating satisfactory reliability and practicability. Thus, the CIA-aptasensor provides an enzyme- and label-free simplified homogeneous system with minimal background interference using isothermal conditions. This study provides a polymerase chain reaction–like approach for enhancing the sensitivity and performance of a biosensor, which could be extended for the application of CIA and label-free signaling strategy to other risk factors. [Display omitted] • CIA-aptasensor owned an enzyme-free, label-free, simplified and homogeneous system. • CHA and HCR-based cascade isothermal amplification was performed. • Ultrasensitive LOD was 0.22 pg mL−1, improved 1368-fold than ELASA. • Minimized background interference by GO, reflected bright fluorescence by SGI. • New guidance of performance improvements for other biosensors might recommend. [ABSTRACT FROM AUTHOR]

The abuse of 17β-estradiol(E2) has aroused wide concern in environmental and biomedical fields, which severely affects the endocrine function of human and animals. Therefore, an ultrasensitive and accurate assay of E2 is critically important. Traditional chromatography or immunoassay techniques exhibited good sensitivity and selectivity, but expensive instruments and antibodies may pose cost and stability issues, as well as difficulties in meeting on-site detection requirements. Ultrasensitive, reliable, and on-site detection of E2 at trace level remains a challenge. Hence, developing a simple, ultrasensitive assay to simultaneously achieve accurate detection and rapid visual analysis of E2 is extremely crucial. We developed a versatile dual-mode photoelectrochemical (PEC) and colorimetric biosensor based on isothermal nucleic acid amplification strategy for the ultrasensitive and accurate detection of E2. The method modified titanium dioxide (TiO 2) with tungsten selenide (WSe 2) nanoflowers to synthesize WSe 2 /TiO 2 heterostructures as a substrate for signal amplification and nanoprobe modification. Isothermal nucleic acid amplification strategy has been proven to be a powerful tool for strong signal amplification. The presence of a target triggered the nucleic acid amplification reaction, and produced a large amount of tDNA that competed with G-quadruplex immobilized on the electrode surface. The remaining G-quadruplex/hemin catalyzed the 4-chloro-1-naphthol (4-CN) to form biocatalytic precipitation (BCP) and ABTS-H 2 O 2 chromogenic reaction, thus, the dual-mode platform was capable of achieving PEC-colorimetric ultrasensitive detection based on the catalytic activity of G-quadruplex/hemin DNAzyme. Within optimal conditions, the dual-mode biosensor exhibited a remarkable detection limit as low as 0.026 pM. Benefiting from the superior performance of WSe 2 /TiO 2 and the power signal amplification of isothermal nucleic acid amplification strategy, this aptasensor achieved the ultrasensitive detection of E2. The independent transmission paths of photoelectrochemical and colorimetric provide mutual support and flexible switching, significantly enhancing the overall sensitivity and accuracy of the detection strategy, which can meet the needs for E2 precise quantification and rapid on-site detection. [Display omitted] • WSe 2 /TiO 2 enhanced PEC performance as a novel photoelectric material. • The nucleic acid amplification strategy significantly improves the sensitivity. • The dual-mode sensing mutually improved the detection accuracy for 17β-estradiol. • The biosensor exhibited a low detection limit of 0.026 pM. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has highlighted the need for rapid and sensitive detection of SARS-CoV-2. Here, we report an ultrasensitive SARS-CoV-2 immunosensor by integration of an AlGaN/GaN high-electron-mobility transistor (HEMT) and anti-SARS-CoV-2 spike protein antibody. The AlGaN/GaN HEMT immunosensor has demonstrated the capability to detect SARS-CoV-2 spike proteins at an impressively low concentration of 10−22 M. The sensor was also applied to pseudoviruses and SARS-CoV-2 ΔN virions that display the Spike proteins with a single virion particle sensitivity. These features validate the potential of AlGaN/GaN HEMT biosensors for point of care tests targeting SARS-CoV-2. This research not only provides the first HEMT biosensing platform for ultrasensitive and label-free detection of SARS-CoV-2. [ABSTRACT FROM AUTHOR]

The isolation and identification of pathogenic bacteria from a variety of samples are critical for controlling bacterial infection-related health problems. The conventional methods, such as plate counting and polymerase chain reaction-based approaches, tend to be time-consuming and reliant on specific instruments, severely limiting the effective identification of these pathogens. In this study, we employed the specificity of the cell wall-binding (CBD) domain of the Staphylococcus aureus bacteriophage 80 alpha (80α) endolysin towards the host bacteria for isolation. Amidase 3-CBD conjugated magnetic beads successfully isolated as few as 1 × 102 CFU/mL of S. aureus cells from milk, blood, and saliva. The cell wall hydrolyzing activity of 80α endolysin promoted the genomic DNA extraction efficiency by 12.7 folds on average, compared to the commercial bacterial genomic DNA extraction kit. Then, recombinase polymerase amplification (RPA) was exploited to amplify the nuc gene of S. aureus from the extracted DNA at 37 °C for 30 min. The RPA product activated Cas12a endonuclease activity to cleave fluorescently labeled ssDNA probes. We then converted the generated signal into a fluorescent readout, detectable by either the naked eye or a portable, self-assembled instrument with ultrasensitivity. The entire procedure, from isolation to identification, can be completed within 2 h. The simplicity and sensitivity of the method developed in this study make it of great application value in S. aureus detection, especially in areas with limited resource supply. [ABSTRACT FROM AUTHOR]

Peanut allergy has garnered worldwide attention due to its high incidence rate and severe symptoms, stimulating the demand for the ultrasensitive detection method of peanut allergen. Herein, we successfully developed a novel electrochemical aptasensor for ultrasensitive detection Ara h1, a major allergenic protein present in peanuts. A conductive nickel atoms Anchored Hydrogen-Bonded Organic Frameworks (PFC-73-Ni) were utilized as excellent electrocatalysts toward hydroquinone (HQ) oxidation to generate a readable current signal. The developed electrochemical aptasensor offers wide linear range (1–120 nM) and low detection limit (0.26 nM) for Ara h1. This method demonstrated a recovery rate ranging from 95.00% to 107.42% in standard addition detection of non-peanut food samples. Additionally, the developed electrochemical method was validated with actual samples and demonstrated good consistency with the results obtained from a commercial ELISA kit. This indicates that the established Ara h1 detection method is a promising tool for peanut allergy prevention. • A novel biosensor was constructed using aptamers and HOF for Ara h1 detection. • This sensor offers low detection limit (0.26 nM) and wide linear range (1–120 nM). • Method was used to test 45 actual samples with good accuracy. [ABSTRACT FROM AUTHOR]

Principle of An rolling circle amplification-assisted CRISPR/Cas12a for HbA1c detection: [Display omitted] • The clever combination of magnetic beads, antibody and rolled loop amplification improves sensitivity. • The PAM sequence on the double-stranded DNA specifically recognized by CRISPR Cas12a is split into two parts. • High sensitivity, high specificity, short detection time, simple operation. • The detection limit in buffer is 0.129 pg/mL. The detection limit in serum is 0.317 pg/mL. Glycated hemoglobin (HbA1c) has been extensively studied as a pivotal marker for monitoring and diagnosing diabetes. In this study, we introduce a highly sensitive and rapid enzyme-catalyzed rolling circle amplification (RCA)-assisted nicked-PAM CRISPR/Cas12a assay (termed "RANPC"). The RANPC system initially recognizes and captures the target using immunomagnetic beads and antibodies, forming a sandwich structure. The antibodies, upon ligating the primers, trigger the RCA reaction, resulting in the generation of single-stranded DNA with numerous repetitive sequences. The product strand of RCA then initiates the trans -cutting activity of nicked-PAM CRISPR/Cas12a, ultimately reporting the target concentration through fluorescent signaling. This study combines dual antibody capture, signal amplification through RCA, and signal output by Cas12a, resulting in high sensitivity, high specificity, and high signal-to-noise ratio. Moreover, the strategic incorporation of an incomplete PAM design in the CRISPR/Cas12a system substantially reduces background interference and enhances assay specificity relative to previous conventional Cas12a detection methods. RANPC possesses advantages such as ultra-sensitivity (with the lowest detection limit up to 0.129 pg/mL and a linear range of 12.8 pg/mL to 1 µg/mL), high specificity, rapid reaction time (approximately 50 min), and straightforward operation. Under optimized experimental conditions, we successfully detected HbA1c in eight real-world blood samples, and the results were in good agreement with the theoretical values. This suggests that this method holds promise as a new approach for the analysis of HbA1c levels in the clinical setting. [ABSTRACT FROM AUTHOR]

A combination of SiO 2 @AuNPs@PDA molecularly imprinted and surface-assisted laser desorption/ionization–time-of-flight mass spectrometry (SALDI–TOF MS) was devised as a method for highly specific and ultrasensitive detection of two biogenic amines—histamine (HIS) and tryptamine (TRP)—in real samples. In this strategy, AuNPs modified amino-abundant silica nanospheres (SiO 2 @AuNPs). The prepared SiO 2 @AuNPs were used as a substrate to synthesize a molecularly imprinted polymer (MIP) through in situ dopamine self-polymerization with HIS and TRP as the template molecules (SiO 2 @AuNP@PDA-MIP). The as-prepared MIP structure, properties, and target-analyte identification conditions were characterized and optimized and it was used as the matrix for MS. Compared to the case of nonimprinted materials, the imprinting function endowed the matrix with a higher selectivity for capturing the target molecules. The enriched analytes were directly and rapidly identified using SALDI–TOF MS without elution. Meanwhile, the proposed method has low background interference, good reproducibility and stability, high salt tolerance, and satisfactory linearity (R2 > 0.99), and it enables ultrasensitive detection of HIS and TRP (limits of detection for HIS and TRP were 0.2 and 0.1 ng mL−1, respectively). Moreover, the proposed method was applied to analyze samples of real beer, sausage, and chicken, and the results agreed with those obtained via liquid chromatography–MS, suggesting that the method has excellent practical applications in the field of food safety. Integration of double template MIP and SALDI-TOF MS was developed for simple, rapid, highly selective and sensitive identification of two BAs in real samples. [Display omitted] • Integration of MIP and SALDI-TOF MS for simple, rapid and highly selective and sensitive detection of BAs. • The imprinted sites in adsorbents can selectivity enrich targtet analytes. • The enriched anlytes-MIP can be directly analysized, while no elution. • The good biocompatibility of PDA-imprinted material contributes to satisfactory reproducibility. [ABSTRACT FROM AUTHOR]

• Metribuzine is a commonly used triazinone herbicide and should be monitored rigorously in terms of food and environmental safety. • Surface enhanced raman spectroscopy which utilises conductive nano particles enables detection of metrubizine at even ultra low concentrations. • SERS method does not require any expensive consumables and provides the analysis results in a few seconds. • Ag nanocubes which are synthesized for detection of metrubizine at ultra low concentrations displayed an excellent performance in terms of chemical stability, reproducibility and sensitivity. Metribuzin, which is a triazinone herbicide, is extensively used in agricultural activities in order to control the spread of broad leaved weeds and grasses. This herbicide is treated as a hazardous chemical, since it multiplies the contamination in the ecosystem by infiltrating to groundwater and soil layers. Thus, detection of Metribuzin in even low concentrations is of vital importance. To date, analytical methods such as High Performance Liquid Chromatography (HPLC), reversed-phase thin-layer chromatography (RP-TLC) with UV absorption detection, Gas chromatography, and Mass spectrometry were utilized in order to detect Metribuzin. At this point, Surface Enhanced Raman Spectroscopy (SERS), while being not as analytical as the methods discussed above, emerges as a significant alternative, since it requires almost no consumables, requires a very short time for analysis and it allows on site analysis. In this study Ag nanocubes were synthesized as a SERS substrate and They were utilized for detection of Metribuzin at concentrations from 10−3 to 10−10 M. Reproducibility, sensitivity and chemical stability tests exhibited that Ag nanocubes were excellent candidates of SERS substrates by allowing detection at ultra- low concentrations up to 10−10 M. [Display omitted] [ABSTRACT FROM AUTHOR]

The detection of melanoma circulating biomarker in liquid biopsies is current under evaluation for being potentially utilized for earlier cancer diagnosis and its metastasis. Herein, we developed a non-invasive electrochemical approach for ultrasensitive detection of the S100B, serving as a potential promising blood circulating biomarker of melanoma, based on an aggregation-induced signal amplification (AISA) strategy via in-situ peptide self-assembly. The fundamental principle of this assay is that the designed amphiphilic peptides (C 16 -Pep-Fc), fulfilling multiple functions, feature both a recognition region for specific binding to S100B and an aggregation (self-assembly) region for the formation of peptide nanomicelles under mild conditions. The C 16 tails were encapsulated within the hydrophobic core of the aggregates, while the relatively hydrophilic recognition fragment Pep and Fc tag were exposed on the outer surface for subsequent recognition of S100B and signal output. AISA provided remarkable accumulation of electroactive Fc moieties that enabled ultrasensitive S100B detection of as low as 0.02 nM, which was 10-fold lower than un-amplified approach and better than previously reported assays. As a proof-of-concept study, further experiments also highlighted the good reproducibility and stability of AISA and demonstrated its usability when applied to simulated serum samples. Hence, this work not only presented a valuable assay tool for ultrasensitive detecting protein biomarker, but also advocated for the utilization of aggregation-induced signal amplification in electrochemical biosensing system, given its considerable potential for future practical applications. An aggregation-induced signal amplification (AISA) strategy based on in-situ peptide self-assembly is developed for ultrasensitive electrochemical detection of melanoma biomarker. The designed amphiphilic peptide can fulfill multiple functions including both specific recognition for biomarker S100B binding and aggregation to enhance the loading capacity of signal tags (Fc) for signal enhancement, resulting in 10-fold decrease in the detection limit. [Display omitted] • A new aggregation-induced signal amplification based on in-situ peptide self-assembly. • Simultaneous signal amplification and specific recognition due to amphiphilic peptide. • The ability to achieve reduced time-cost and improved detection efficiency. • The signal amplification strategy displays 10-fold higher than un-amplified strategy. [ABSTRACT FROM AUTHOR]

[Display omitted] • A multi-layer architecture of NiMOFs was synthesized and characterized by SEM, XRD, XPS, Raman, IR, and EIS. • The insertion of helical-shaped MWCNTs into NiMOFs has been done for enhanced electrocatalytic sensing applications. • The surface adsorption efficiency of the different modified electrodes was discussed. • The designed binder-free (GCE/MWCNT@NiMOFs) electrochemical probe exhibited a satisfactory limit of detection and wide linear response. • The designed electrochemical probe was successfully employed in real-world samples and achieved excellent recovery ranges with high reproducibility. Nitroimidazole-based drugs are widely used as an antibiotic for the treatment of anaerobic bacterial and parasite illnesses. The widespread use of these drugs in animal feed and the consequent environmental pollution have become significant concerns in recent years. Simple, sensitive, and rapid detection of the antibody in various real samples is demanding research interest. Herein, we report a Nickel-metal organic framework functionalized Multiwalled Carbon nanotubes modified glassy carbon electrode (MWCNT@NiMOFs) as an ultrasensitive and rapid voltammetric sensor for the detection of ornidazole (ORDZ) in a neutral pH solution. The MWCNT@NiMOFs were prepared using a microwave-assisted solvothermal technique accompanied by an ultrasonication method. The designed MWCNT@NiMOFs offered a low charge transfer resistance (R ct) of 141 Ω along with excellent electrocatalytic activity, and high current density at the lowered cathodic peak potential (-0.62 V vs Ag/AgCl) for ORDZ detection. The surface adsorption capacity (Γ s) in terms of surface excess and heterogeneous charge transfer rate constant (k 0) of the MWCNT@NiMOFs were calculated to be 3.29 × 10-9 mol cm−2 and 5.33 × 10-3 cm s−1, respectively. Under an optimal working condition, differential pulse voltammetry measurements of ORDZ have shown concentration linearity in a window, 100 nm to 10 µM range with excellent sensitivity, 5.69 × 10-5A µM−1 cm−2, and detection limit, 26 nM (3.3/s). The designed MWCNT@NiMOFs offered appreciable reproducibility, and repeatability up to 30 days of storage time. The real-time quantitative evaluation of ORDZ in human urine and tap water specimens was done along with ∼ 100 % recovery values. Since the new approach is simple, selective, and separation-free, it can be extendable to a variety of real-time practical applications. [ABSTRACT FROM AUTHOR]

Ultrasensitive analytical methods are still urgent for the discovery of trace level biomarkers and the early clinical diagnosis of disease. In this work, an ultrasensitive universal sensing platform was constructed by integrating fluorescent assay with chemical-chemical redox cycling signal amplification strategy. Using Ru@SiO 2 nanoparticles wrapped by MnO 2 nanosheets (Ru@SiO 2 @MnO 2) as fluorescent probe, the chemical-chemical redox cycling system was conducted upon ascorbic acid (AA) and tris(2-carboxyethyl)phosphine (TCEP) as reductants and MnO 2 nanosheets as oxidant. The MnO 2 nanosheets not only could quench the fluorescence of Ru@SiO 2 nanoparticles to reduce the background, but also could serve as oxidants to react with AA, generating dehydroascorbic acid (DHA). The DHA was reduced by TCEP in turn to form AA that participated in the next cycling of chemical-chemical redox reaction. Thus, the constantly released AA from the chemical-chemical redox cycling system could massively etch MnO 2 nanosheets on Ru@SiO 2 surface, making the fluorescence of Ru@SiO 2 nanoparticles greatly recovered. It was shown that the sensitivity of the fluorescent assay was improved almost 52 times by utilizing the chemical-chemical redox cycling signal amplification strategy. This strategy was further employed to detect DNA methylation with the aid of AA-encapsulated liposomes that were modified with 5 mC antibodies to bind with the methylated DNA captured in 96-well plate. A detection of limit down to 16.2 fM was achieved for the detection of methylated DNA. It's believed that the incorporation of chemical-chemical redox cycling signal amplification strategy into fluorescent sensing paves a new way for ultrasensitive detection of biomarkers. Liposome assisted chemical-chemical redox cycling signal amplification for ultrasensitive fluorescent detection of DNA methylation. [Display omitted] • Chemical-chemical redox cycling signal amplification strategy was firstly integrated into fluorescent sensing. • The sensitivity of fluorescent assay was improved almost 52 times. • This proof-of-concept was employed to detect of DNA methylation with the assistance of liposomes. • A detection limit (LOD) down to 16.2 fM was achieved for methylated DNA detection. [ABSTRACT FROM AUTHOR]

Signal amplification is a key step that determines the sensitivity of molecular assays. Although studies on aptamers have mostly focused on their target-binding ability, taking advantage of the gene-coding function of nucleic acids, we demonstrate here that aptamers can be engineered into diagnostic reagents that can both recognize a target and generate highly amplified detection signals. We developed a strategy that employs a 'readable' aptamer that consists of a single-stranded aptamer and a double-stranded reporter gene. After binding to its target via the aptamer region, the reporter gene of the readable aptamer produces amplified number of signal-generating enzymes through a subsequent in vitro expression reaction. In contrast to conventional enzyme-conjugation methods, this method allows the generation of far more amplified detection signals, thereby markedly increasing the sensitivity of detection enough to analyze a target present in aM concentrations. Image 1 • Efficiency of signal amplification determines the sensitivity of a bioassay method. • Compared to antibodies, aptamers carry substantial advantages, including lower production cost and higher stability. • Readable aptamers can both recognize and produce amplified number of signal-generating enzymes. • The ALIVE assay that employs the readable aptamers could detect thrombin present in attomolar concentrations. [ABSTRACT FROM AUTHOR]

The development of a rapid and sensitive method for the detection of fluoride ion (F−) in aqueous systems is of great significance for human health and environmental monitoring. In this study, a zirconium porphyrinic luminescent metal-organic framework (LMOF), PCN-222, was employed as a novel fluorescent probe for the ultrasensitive, rapid and selective detection of F− in water. The PCN-222 probe was prepared by a facile solvothermal method. It exhibited good fluorescence stability and was highly stable in water. The fluorescence emission of PCN-222 could be effectively and selectively quenched by F− due to the strong coordination affinity of F− to the zirconium clusters in PCN-222. The proposed fluorescence method for F− detection based on PCN-222 probe afforded a linear response range of 1–20 μmol/L and a very low detection limit (0.048–0.065 μmol/L) in reference to many reported F− fluorescent probes. Moreover, a rapid response time (<10 s) was obtained due to the open and uniform pore structure of PCN-222 that allowed the fast diffusion of F− to interact with the zirconium recognition sites. Finally, the PCN-222 probe was successfully applied for the fluorescence detection of F− in real water samples. These results highlight the great application potential of LMOF in the sensing fields. Image 1 • Highly stable zirconium-based LMOF (PCN-222) was successfully applied in F− detection in water. • PCN-222 afforded very short F− response time (<10 s) due to its open and uniform pore structure. • The LOD was markedly lower than WHO and US EPA guidelines and many reported F− sensors. [ABSTRACT FROM AUTHOR]

Flexible fiber-shaped microelectrode biosensors have aroused intensive attention due to the promising use for monitoring personal healthcare. However, challenges still exist in the pursuit of combination of high sensitivity and selectivity. Herein, a facile and effective strategy to solve these problems was proposed by developing a novel fiber-shaped photoelectrochemical urea biosensor (PUB) based on highly flexible graphene (G) fiber. The remarkable combined features of the resulting PUB with high surface roughness, good transmittance and superior molecular recognition could contribute to good adsorption capacity, convenient light absorption and selective detection, thus boosting a wide linear range from 0.01 to 1500 μM and a low detection limit of 1 nM. Meanwhile, rapid response, outstanding selectivity and perfect working performance during bending were available as expected. This research provides useful guidelines for designing and fabricating flexible microelectrode biosensors with high sensing performance toward future uses. Flexible fiber-shaped microelectrode biosensors with high surface roughness, significant transmittance and superior molecular recognition, which are fabricated by the uniform intercalation of TiO 2 nanoparticles between graphene sheets and molecular imprinting strategy, show high sensitivity, selectivity and bending stability. Image 1 [ABSTRACT FROM AUTHOR]

[Display omitted] • A lysosome-targeting ultrasensitive Cys fluorescent probe 1 was designed. • Probe 1 exhibits red-emission, high selectivity and sensitivity and low LOD (2.93 nm). • Probe 1 is capable of fluorescence imaging of s Cys in living cells. • Probe 1 realizes tumor imaging with good biological safety. Developing efficient strategies for specific detection of cysteine (Cys) is of great importance for identifying complicated biological roles in physiological and pathological processes. Herein, an ultrasensitive red-emission fluorescent probe (termed 1) is constructed for specific detection and biological visualization of Cys. The linked-anthocyanin fluorophore modified with a twisted N, N-diethylamino moiety shows improved red-shifted emission (642 nm) and absolute quantum yield (0.224 in dimethyl sulfoxide), as well as minimal fluorescence background signal and good water solubility. Meanwhile, utilizing acryloyl chloride as recognition group endows the probe 1 with excellent sensitivity and selectivity towards Cys (limit of detection: 2.93 nM). More importantly, the in vitro and in vivo results confirm that the probe 1 has the capacity of fluorescence imaging of Cys and good biological safety, which holds great promise for bioanalysis and biosensing of Cys. [ABSTRACT FROM AUTHOR]

Heavy metal ions (HMIs), including Pb2+, Cu2+, and Hg2+, has shown great threat to the environment and public health worldwide owing to their high toxic at trace levels. However, conventional laboratory-based methods for analyzing HMIs require expensive instrumentation and complex operations limit their further application. In this study, we present a novel "two-step" approach based on entropy-driven multicolor DNA nanoflowers (DNFL) for the simultaneous ultrasensitive detection of three typical HMIs (Pb2+, Cu2+, and Hg2+). Through specific cleavage/competition reactions initiated by the target metal ions, a large number of single-stranded DNA (ssDNA) are produced, triggering the blooming of DNFL. Subsequently, with the assistance of fuel strands, an entropy-driven strand displacement reaction (ESDR) will further accelerate the conformational change of DNFL within one hour. Different fluorophores (FAM, ROX, and Cy5) attached to the opened DNFL serve as indicator molecules for the respective HMIs. After reasonable design and optimization, the developed fluorescence analysis method demonstrates excellent analytical performance (with limit of detection, 0.13 nM, 3.5 pM, 4.6 pM for Pb2+, Cu2+, and Hg2+, respectively) and can be applied to the simultaneous and rapid detection of multiple HMIs in water environment. • An entropy-driven DNA sensor based on a multicolor DNA nanoflower was developed. • The biosensor can realize the detection of multiple HMIs in water through a simple "two-step" approach. • The flexible architecture and precise probe arrangement achieve stable output of fluorescence signals. • The method exhibits satisfactory performance for rapid detection of multiple HMIs in water environments. [ABSTRACT FROM AUTHOR]

A bismuth oxide- nitrogen doped reduced graphene oxide/glassy carbon electrode (Bi 2 O 3 -NRGO/GCE) was prepared for the detection of the flavonoid drug chrysin in pharmaceutical capsules, for the first time. [Display omitted] • Bi 2 O 3 nanosheet materials were synthesized by a hydrothermal method. • Bi 2 O 3 -NRGO/GCE were used to construct sensors for the detection of chrysin. • A linear range (0.01–10 μM) and LOD (2 nM) for chrysin detection were achieved. • The sensors were used for the ultrasensitive determination of chrysin in pharmaceutical preparations. A bismuth oxide- nitrogen doped reduced graphene oxide/glassy carbon electrode (Bi 2 O 3 -NRGO/GCE) was prepared for the detection of the flavonoid drug chrysin in pharmaceutical capsules, for the first time. Bi 2 O 3 nanosheets synthesized by a hydrothermal method, were ultrasonically mixed with NRGO, and a simple and efficient Bi 2 O 3 -NRGO/GCE composite was prepared. The composites were characterized by various methods. Cyclic voltammetry and electrochemical impedance techniques were used to study the electrochemical sensing performance of the composites-modified electrode surface. The electrochemical performance and optimal detection conditions of chrysin on Bi 2 O 3 -NRGO/GCE were investigated by differential pulse voltammetry (DPV). The oxidation peak current of chrysin has a linear relationship with its concentration, in the range of 0.01–10 μM, with a detection limit of 2.0 nM. Bi 2 O 3 -NRGO/GCE also has good selectivity for chrysin, which is not interfered with by common inorganic salts and common organic substances, or by structurally similar substances. The composite electrode also has good repeatability, reproducibility and stability. It shows that utilizing Bi 2 O 3 and NRGO binary complexes modified electrodes for ultrasensitive chrysin sensing is a simple and convenient detection method, with promising applicability in the development of pharmaceutical component sensing technology. [ABSTRACT FROM AUTHOR]

Herein, a spatial confined enzyme-linked immunoassay (ELIA) is developed for ultrasensitive biomarker detection using a microfluidic magnetic delivery (μMD) disc. In μMD-ELIA, magnetic immunocomplexes are delivered into microchannel and trapping/preconcentration in the microchamber of μMD disc for fluorescence detection. The microchamber offers a confined space both for effective magnetic preconcentration and accelerated concentration of enzyme products. After μMD disc optimization, the assay performances of μMD-ELIA have been evaluated by model targets of human monocyte differentiation antigen cluster of differentiation14 (CD14) and interleukin (IL)–8. The limits of detection (LOD) of μMD-ELIA for CD14 and IL-8 are 0.17 pg/mL and 0.012 pg/mL, respectively, which corresponded to an over 300-fold LOD sensitivity enhancement compared to their standard ELISA results. In human serum analysis, good accuracy is obtained on both CD14 and IL-8 when compared to the results of ELISA kits, and satisfied recoveries of 81.3–112 % with RSDs of 1.0–9.7 % for IL-8 were obtained. Moreover, the μMD-ELIA is than applied to IL-6 concentration variation monitor in rat plasma during the progression of inflammatory reaction successfully, which further confirmed that the μMD-ELIA has enormous potential in disease early diagnosis and curative effect monitoring. [Display omitted] • A μMAD disc having special confined microchamber designed and fabricated. • The microchamber enhanced magnetic enrichment and concentration of enzyme products. • The μMAD-ELIA performed about 300 times LOD improvement over standard ELISA. • μMAD-ELIA applied to trace-level biomarkers detection and monitoring in plasma. [ABSTRACT FROM AUTHOR]

[Display omitted] • AgNP/MWCNT hybrid material was developed as ultra-sensitive SERS substrate. • Cholesterol molecule detected quickly and reliably. • This method was applied to the detection of cholesterol in milk samples. • Much lower LOD value achieved with SERS. Cholesterol is vital for living things because of an important part of cell membranes, as well as one of the basic components of brain and nerve cells. However, cholesterol must be at an optimum level. If it is below or above this level, it is a marker of many various diseases. Therefore, the detection of cholesterol amount is very important. Herein, MWCNTs were synthesized and AgNPs were grown on their surfaces. Thus, AgNP/MWCNT hybrid material was obtained. The AgNP/MWCNTs were used as surface enhancement Raman scattering (SERS) substrate to quantify the cholesterol molecule. High SERS enhancement of AgNP/MWCNT, specific SERS sensing platform and high sensitive SERS substrate were proposed to determine and monitor cholesterol molecule. AgNP/MWCNT substrate was studied in the concentration range of 10−3–10−10 M and the limit of detection (LOD) was calculated as 3.24 × 10−11 M. In addition, the enhancement factor (EF) was determined as 6.21 × 109. As a result, it was reported in this study that cholesterol molecule can be determined with excellent accuracy, precision and sensitive by using AgNP/MWCNT substrate and therefore it can provide great potential in clinical diagnosis and health management. [ABSTRACT FROM AUTHOR]

As a promising biomarker, the level of methylated DNA usually changes in the early stage of the cancer. Ultrasensitive detection of the changes of methylated DNA offers possibility for early diagnosis of cancer. In this work, a tannic acid-accelerated Fenton chemical reaction amplification was firstly proposed for the construction of ultrasensitive fluorescent assay. Tannic acid was used as reductant to accelerate Fenton reaction procedure through the conversion of Fe3+/Fe2+, generating hydroxyl radicals (·OH) continuously. The produced ·OH oxidized massive non-fluorescent terephthalic acid (TA) to fluorescent-emitting hydroxy terephthalic acid (TAOH). In this way, the fluorescent signal could be greatly enhanced and the sensitivity was improved almost 116 times. The proposed signal amplification strategy was further applied to detect of DNA methylation with the assistance of liposome encapsulated with tannic-Fe3+ complexes. The methylated DNA was firstly captured through the hybridization with its complementary DNA that were pre-modified in the 96-well plate via the combination between streptavidin (SA) and biotin. Then, 5 mC antibody on the surface of liposomes specially recognized and combined with methylation sites, which brought large amount of tannic-Fe3+ complexes to participate Fenton reaction. The fluorescence of generated TAOH was depended on the concentration of methylated DNA. The assay showed good analytical performance for methylated DNA with a limit of detection (LOD) of 1.4 fM. It's believed that tannic acid-accelerated Fenton chemical reaction amplification strategy provides a promising platform for ultrasensitive fluorescent detection of low abundant biomarkers. [Display omitted] • A tannic acid-accelerated Fenton chemical reaction amplification was proposed to construct ultrasensitive fluorescent assay. • The sensitivity was improved almost 116 times. • It was employed to detect of DNA methylation with the assistance of liposomes. • The assay showed a low detection limit (LOD) of 1.4 fM for methylated DNA detection. [ABSTRACT FROM AUTHOR]

Biomarkers are the most sensitive reactants and early indicators of many kinds of diseases. The development of highly sensitive and simple techniques to quantify them is challenging. In this study, based on rolling cycle amplification (RCA) and the Nicked PAM/CRISPR-Cas12a system (RNPC) as a signal reporter, a sandwich-type method was developed using antibody@magnetic beads and aptamer for the high-sensitive detection of the C-reactive protein (CRP). The antibody-antigen (target)-aptamer sandwich-like reaction was coupled to RCA, which can produce hundreds of similar binding sites and are discriminated by CRISPR/Cas12a for signal amplification. The ultrasensitivity is achieved based on the dual-signal enhancing strategy, which involves the special recognition of aptamers, RCA, and trans -cleavage of CRISPR/Cas12a. By incorporating the CRISPR/Cas12a system with cleaved PAM, the nonspecific amplification of the RCA reaction alone was greatly reduced, and the dual signal output of RCA and Cas12a improved the detection sensitivity. Our assay can be performed only in two steps. The first step takes only 20 min of target capture, followed by a one-pot reaction, where the target concentration can be obtained by fluorescence values as long as there are 37 °C reaction conditions. Under optimal conditions, this system detected CRP with high sensitivity. The fabricated biosensor showed detection limits of 0.40 pg/mL in phosphate-buffered saline and 0.73 pg/mL in diluted human serum and a broad linear dynamic range of 1.28 pg/mL to 100 ng/mL within a total readout time of 90 min. The method could be used to perform multi-step signal amplification, which can help in the ultrasensitive detection of other proteins. Overall, the proposed biosensor might be used as an immunosensor biosensor platform. [Display omitted] • The clever combination of magnetic beads, aptamers and rolled loop amplification improves sensitivity. • Three Designed ssDNA are combined with RCA products to bring the split PAM together to Initiate Cas12a activity. • High sensitivity, high specificity, short detection time, simple operation. • The detection limit in buffer is 0.40 pg/mL. The detection limit in serum is 0.73 pg/mL. [ABSTRACT FROM AUTHOR]

Development of specific signal reporters with signal amplification effect are highly needed for sensitive and accurate detection of pathogen. Herein, we design a colorimetric immunosensing nanosystem based on liposome encapsulated quantum dots-sized MnO 2 nanozyme (MnO 2 QDs@Lip) as a signal reporter for ultrasensitive and fast detection of SARS-CoV-2 antigen. The pathogenic antigens captured and separated by antibody-conjugated magnetic beads (MBs) are further connected with antibody-modified MnO 2 QDs@Lip to form a sandwich-like immunocomplex structure. After triggered release, MnO 2 QDs efficiently catalyze colorless 3,3′,5,5′-tetramethylbenzidine (TMB) to blue oxidized TMB, which can be qualitatively observed by naked eyes and quantitatively analyzed by UV–Vis spectra or smartphone platforms. By taking advantages of immuno-magnetic separation, excellent peroxidase-like catalytic activity of MnO 2 QDs, and high encapsulation efficiency of MnO 2 QDs@Lip, ultrasensitive detection of SARS-CoV-2 antigen ranging from 0.1 pg/mL to 100 ng/mL is achieved within 20 min. The limit of detection (LOD) is calculated to be 65 fg/mL in PBS buffer. Furthermore, real clinical samples of SARS-CoV-2 antigens can be effectively identified by this immunosensing nanosystem with excellent accuracy. This proposed detection nanosystem provides a strategy for simple, rapid and ultrasensitive detection of pathogens and may shed light on the development of new POCT detection platforms for early diagnosis of pathogens and surveillance in public health. [ABSTRACT FROM AUTHOR]

A simple and efficient electrochemical sensing platform for simultaneous detection of hydroquinone (HQ), catechol (CC) and resorcinol (RC) based on in-situ prepared sodium hydroxide (NaOH) nanorods was reported for the first time. Sodium hydroxide (NaOH) nanorods on glassy carbon electrode (GCE) was synthesized via one electrochemical deposition step in NaOH solution using constant current. The affecting factors including content of NaOH solution, deposition current and deposition time were investigated. The obtained electrodes were also examined by scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). The electrochemical behaviour analysis and dynamic study indicated that the three dihydroxybenzene isomers can be catalytically oxidized and discriminated simultaneously on the proposed electrode. Using square wave voltammetry (SWV), the ultrasensitive and simultaneous detection of HQ, CC and RC was realized with wide linear range from 0.03 to 1500 μM and low detection limit of 0.01, 0.01, 0.09 μM, respectively. The detection of them in real water samples was also successfully performed and good recovery was obtained. Image 102308 • Simultaneous detection of HQ, CC and RC was realized based on NaOH nanorods/GCE. • The nano-NaOH/GCE was synthesized via electrochemical deposition for seconds. • The effect of deposition current, time and content of NaOH solution were investigated. • The LODs of HQ, CC and RC were much lower than previous reports. • The detection in real water samples was successfully performed. [ABSTRACT FROM AUTHOR]

A novel mushroom-like electrochemical immunoassay for the ultrasensitive detection of histone acetyltransferase activity (HAT p300) has been established on account of the new composite graphene oxide (GO) nanolayer. The immunoassay involves immobilization of substrate peptide onto Au electrode, acetylation in lysine of substrate peptide, and the interaction between acetyl group of lysine and acetyl-antibody (Ab Ac) of the GO nanolayer. The GO nanolayer comprises large amounts of methylene blue molecules (MB), giving rise to large signal amplification. Only in the presence of HAT p300, an obvious electrochemical signal appears and the peak linear current is proportion to the HAT p300 concentrations ranging from 0.01 to 150 nM with a detection limit of 0.0036 nM. The great enhancement on sensitivity of the proposed mushroom-like immunosensor derives from both the constructed Faraday cage and the extended outer Helmholtz plane (OHP). Further, the immunosensor with excellent sensitivity and selectivity can be applied for the HAT p300 activity detection in Hela cell lysates, serum and urine, hinting an improved and splendid analytical performance. Briefly, this stable, simple and ultrasensitive electrochemical immunoassay has considerable promise for further applications in the HATs-interrelated epigenetic studies and drug development. A novel mushroom-like electrochemical immunosensor for the ultrasensitive detection of histone acetyltransferase activity (HAT p300) has been reported, which shows promise for further applications in the HATs-targeted epigenetic research and drug discovery. Image 1 • An ultrasensitive mushroom-like electrochemical immunosensor is developed. • The proposed strategy can be applied for probing the HAT p300 activity. • The detection sensitivity of the novel method is improved sharply. • Mechanism is the constructed Faraday cage and extended outer Helmholtz plane. • The HAT-based immunosensor is also adopted for the screening of inhibitor. [ABSTRACT FROM AUTHOR]

Abstract The sensitive detection of tumor proto-oncogenes is indispensable because the early diagnosis and accurate treatment of genetic diseases is the key guarantee of patients' health. In this study, we proposed a novel palindromic molecular beacon (PMB) that it bases on the signal amplification strategy for ultrasensitive detection of Kras gene codon 12. PMB is designed to have two palindromic fragments at its two ends, one of which is locked via folding into a hairpin structure and the other promotes the formation of PMB duplex via intermolecular self-hybridization. Target DNA can hybridize to the loop portion of PMB and release the palindromic fragment at the 3' end. Within the PMB duplex, the two palindromic fragments released hybridize with each other and serve as polymerization primer responsible for the strand-displacement amplification (SDA). Namely, hybridized target DNA can be displaced and initiates the next round of reactions, making the polymerization/displacement/hybridization process go forward circularly. As a result, a large number of polymerization products are produced, dramatically enhancing optical signal. Because primer hybridization and polymerization-based displacement occur within PMB duplex, the reaction process is called intramolecular strand-displacement amplification (ISDA). Via utilizing the newly-proposed PMB-based ISDA strategy, the target K-ras gene could be detected down to 10 pM with a wide response range of 1 × 10−11-1.5 × 10−7 M, and point mutations are easily distinguished, realizing the ultrasensitive, highly selective detection of K-ras gene. This impressive sensing paradigm demonstrates a new concept of signal amplification for the detection of disease-related genes only via using a simple way to efficiently amplify optical signal. Graphical abstract Image 1 Highlights • A molecular beacon with two palindromic fragments (PMB) was designed that can self-assemble into a PMB duplex via the hybridization between palindromic fragments for Kras gene codon 12 detection. • On the basis of PMB duplex, the intramolecular strand-displacement amplification (ISDA) concept was proposed to construct a powerful biosensing system for the ultrasensitive detection of cancer-related gene. • Even if only one probe, PMB, was involved in the ISDA sensing system, the target K-ras gene could be detected down to 10 pM with a linear dynamic range of 4 orders of magnitude, and point mutations are easily distinguished. • Several advantages, for example, the impressive assay sensitivity, high selectivity sensing, simple design and convenient assay, make the newly-developed sensing strategy exhibit great promise for the application in the clinic diagnosis and targeted therapy. [ABSTRACT FROM AUTHOR]

Recently, ultrasensitive detection and multi-guest sensing have received extensive attention due to their high sensitivity and efficiency. Herein, we report a novel approach to achieve ultrasensitive detection of multi-analyte. This approach is concluded as "rationally introduce Aggregation-Induced Emission (AIE) into chemosensor". According to this approach, by rationally introducing self-assembly moiety, the obtained chemosensor DNS could serve as a novel AIEgen and show strong AIE in DMSO/H 2 O (water fraction 80%) binary solution. Interestingly, a simple fluorescent sensor array based on the DNS has been developed. This sensor array could selectively sense Fe3+, Al3+, H 2 PO 4 − and L-Arg in water solution. More importantly, this sensor array shows ultrasensitive detection for Fe3+, Al3+ and L-Arg. The LODs of the sensor array for Fe3+, Al3+ and L-Arg are in the range of 3.54 × 10−9 M to 9.42 × 10−9 M. Moreover, H 2 PO 4 − could realize the reversible detection of Fe3+ in the DMSO/H 2 O (water fraction 80%) solution. Meanwhile, DNS -based test papers and thin films were prepared, which could serve as test kits for convenient detection Fe3+, Al3+, and L-Arg in water. In addition, they could also act as efficient erasable fluorescent display materials. Herein, we report a novel approach to achieving ultrasensitive detection of multi-analyte. This approach is concluded as "rationally introduce Aggregation-Induced Emission (AIE) into chemosensor". According to this approach, by rationally introducing self-assembly moiety, the obtained chemosensor DNS could serve as a novel AIEgen and show strong AIE in DMSO/H 2 O (water fraction 80%) binary solution. Interestingly, a simple fluorescent sensor array based on the DNS has been developed. This sensor array could selectively sense Fe3+, Al3+, H 2 PO 4 − and L-Arg in water solution. More importantly, this sensor array shows ultrasensitivity for Fe3+, Al3+ and L-Arg. The LODs of the sensor array for Fe3+, Al3+ and L-Arg are in the range of 3.54 × 10−9 M to 9.42 × 10−9 M. Moreover, H 2 PO 4 − could realize the reversible detection of Fe3+ in the DMSO/H 2 O (water fraction 80%) solution. Meanwhile, DNS -based test papers and thin films were prepared, which could serve as test kits for convenient detection of Fe3+, Al3+, and L-Arg in water. In addition, they could also act as efficient erasable fluorescent display materials. Unlabelled Image • Rationally induce AIE into the small molecular chemosensor. • A simple sensor array for Fe3+, Al3+, H 2 PO 4 - and L-Arg was created. • Ultrasensitive detection for Fe3+, Al3+ and L-Arg in aqueous solutions. • LODs of the sensor array for Fe3+, Al3+ and L-Arg reached 10-9 M. • Fe3+, Al3+, L-Arg test papers and fluorescent display materials were prepared. [ABSTRACT FROM AUTHOR]

Abstract A novel supramolecular organic framework gel (PQPA) has been constructed by a novel bilateral 8-hydroxyquinoline modified pillar[5]arene host (P5Q) and a bilateral bromohexyl functionalized pillar[5]arene guest (P5C6). Interestingly, the gel PQPA shows special selective and ultrasensitive sensing property for Fe3+. The limit of lowest detection (LOD) of gel PQPA for Fe3+ is 0.102 nM. Meanwhile, by adding Fe3+ into the gel PQPA , a no fluorescence Fe3+ coordinated metallogel (PQPA-Fe) could be constructed. Due to the competitive coordination of F−, fluorescent "turn-on" ultrasensitive response of the Fe3+ coordinated metallogel (PQPA-Fe) for F− is achieved. The limit of lowest detection of the Fe3+ coordinated metallogel (PQPA-Fe) for F− is 9.79 nM. In addition, the xerogel of the supramolecular organic framework gel (PQPA) is capable for removing Fe3+ in a lower concentration aqueous solution at an adsorption rate of 99.9%. More importantly, the supramolecular organic framework gel (PQPA) could be used to detect Fe3+ in the Yellow River Water samples. The supramolecular organic framework gel (PQPA) and Fe3+ coordinated metallogel (PQPA-Fe) could act as ultrasensitive reversible fluorescent chemosensor, test kits and fluorescent display materials for Fe3+ and F−. Graphical abstract Novel supramolecular organic framework gel PQPA was constructed by functionalized pillar[5]arenes. Interestingly, the SOF gel PQPA could continuously and ultrasensitively detect Fe3+ and F− in water. Unlabelled Image Highlights • Novel pillar[5]arene-based SOF gel (PQPA) was successfully constructed. • PQPA could carry out ultrasensitive detection of Fe3+ in water (LOD = 0.102 nM). • PQPA-Fe could ultrasensitively detect F− in water (LOD = 9.79 nM). • Fe3+ could be adsorbed by PQPA from water (adsorption rate of 99.9%). • Test kits for Fe3+ and F− were prepared. [ABSTRACT FROM AUTHOR]

Highlights • Gram staining and direct immunoassay were first adopted for S. Enteritidis detection. • The marking signal was derived from one-step bacteria staining with crystal violet. • The device exhibited excellent sensitivity, simplicity, selectivity and feasibility. • Results could be clearly distinguished by naked eyes even under a lower analyte level. Abstract Here, a facile, label-free and sensitive lateral flow strip (LFS) biosensor for foodborne pathogens was established relying on the innovative introduction of Gram staining and the direct immunoreaction. Target bacteria can be directly marked with crystal violet (CV) by one-step staining which is superior to traditional signal marking techniques in LFS assay, and the method's selectivity can be guaranteed by high-specificity monoclonal antibody. With Salmonella Enteritidis (S. Enteritidis) as a model target, this protocol can selectively detect 80 CFU mL−1 S. Enteritidis within 11 min in the optimized conditions. Moreover, with Listeria monocytogenes as another model target, the biosensor shows a high universality for detections of both gram-negative and gram-positive bacteria. The unexpected applicability of biological dye tracer in strip biosensor reveals that the biological dye can be a potential tool serving as a universal signal tracer for pathogenic microorganisms in food safety monitoring and early clinical diagnosis. [ABSTRACT FROM AUTHOR]

Abstract Detection of the Hepatitis-B surface antigen at the attomolar level is demonstrated using antibody functionalized liquid gated ZnO nanorods field effect transistor (FET) biosensor with vertical electrode configuration. The sensor is operated in heterodyne mode at high frequency to overcome the problem of Debye screening effect in physiological analyte. Enhanced penetration of the electric field lines through the nanorods enables significant improvement in the limit of detection and sensitivity compared to that of the conventional lateral electrode configuration. The combined effect of the probable change in the threshold voltage and the carrier mobility for vertical electrode configuration lead to a sensitivity of around 75% at 1 fM (which is an enhancement by 200%) and a detection limit of 20 aM with a dynamic range from 20 aM to 1 pM. The detection limit which is achieved with the proposed label free sensor in physiological analyte using antibodies is lowered by more than three orders of magnitude compared to the existing reports. Highlights • Attomolar detection of HBsAg in serum using ZnO nanorods based liquid gated Bio-FET with vertical electrode configuration. • Enhanced penetration of electric field lines across nanorods elevates sensitivity value than usual lateral electrode pattern. • A change in threshold voltage and carrier mobility, leads to a sensitivity around 66% at 1 fM and a detection limit of 20 aM. [ABSTRACT FROM AUTHOR]

Cost-effective health care technologies for detection of disease biomarkers at ultralow concentrations can significantly improve the quality of life in resource-constrained countries. However, current techniques require expensive instruments, complex conjugation protocols and tedious laboratory procedures that may not be affordable for the major part of the world population. Here, we propose to sidestep the problem by establishing a simple, relatively inexpensive sensing method employing a photonic substrate, a material affinity peptide, and a smart phone CCD detector to achieve detection of clinically relevant proteins in serum at concentrations much lower than standard enzyme-linked immunosorbent assay (ELISA). Easy to process porous silicon (PSi) microcavities were employed as substrates that provide a three-dimensionality, large surface area, and convenient light enhancement properties for molecular detection. Anti-histone H2 B antibodies and biomarkers of severe illnesses are detected in whole serum at concentrations as low as 10 fg mL −1 by using the proposed PSi- ELISA protocol. Due to its easy use, cost effectiveness and high sensitivity, the proposed method has potential large-scale applications in ultrasensitive sensing of different other clinically relevant molecules for early stage diagnostics. [ABSTRACT FROM AUTHOR]

There is an urgent need to develop an economical and convenient method for the ultrasensitive detection of patulin (PAT), a mycotoxin that can potentially harm human health when it is found in fruits and their derivatives. In this study, we have developed a novel fluorescent aptasensor that utilizes nitrogen-doped carbon dots (N-CDs) as the fluorescent donor and hexagonal β-Co(OH) 2 nanoplates as the fluorescent acceptor. N-CDs were synthesized through the hydrothermal method, resulting in spherical particles with a diameter of 7.6 nm. These nanoparticles exhibited excellent water solubility and displayed a vibrant blue emission at 448 nm when excited at 360 nm. Cobalt hydroxide nanoplates with a beta crystal structure [β-Co(OH) 2 ] were synthesized using a simple co-precipitation method, exhibiting hexagonal plate-like shapes with uniform lateral sizes of 4–5 μm. The fluorescence of N-CDs can be efficiently quenched by hexagonal β-Co(OH) 2 nanoplates through Förster resonance energy transfer mechanism. The maximum quenching-recovery capability can be achieved when the concentrations of N-CDs-Apt and β-Co(OH) 2 nanoplates are 150 nmol/L and 100 μg/mL, respectively. The pH of the TE buffer should be 8.0, and the incubation time should be 10 min at 25 °C. The developed fluorescent aptasensor displayed an excellent selectivity for PAT determination with a detection limit of 0.57 pg/mL in the linear range of 1.25 pg/mL-100 ng/mL. The rapid PAT determination in fruit juice samples was realized with good recoveries (96.9–105.8%). The developed fluorescent aptasensor based on the interaction between N-CDs and hexagonal β-Co(OH) 2 nanoplates can be a promising method for the rapid and ultrasensitive detection of PAT in agricultural products. [Display omitted] • Facile preparation of hexagonal β-Co(OH) 2 nanoplates as a new nano-quencher. • Fabrication of a novel aptasensor containing nitrogen-doped carbon dots (N-CDs). • N-CDs-Apt/β-Co(OH) 2 nanoplates-based sensor for patulin detection in fruit juice. • Elucidation of the aptasensing mechanism for selective detection of patulin. [ABSTRACT FROM AUTHOR]

Aflatoxin M1 (AFM1) is highly toxic, widely distributed, and difficult to monitor, posing a serious threat to human health. Therefore, a highly sensitive, rapid, convenient, and low-cost detection method must be urgently established. In this study, a triple strategy-enhanced immunochromatographic assay (ICA) was developed to satisfy these detection requirements. First, a turn-on signal output mode of the fluorescence quenching ICA substituted the turn-off mode of the traditional ICA for sensitive response to trace AFM1, with the limit of detection (LOD) reduced by approximately 4.9-fold. Then, a novel Au and polydopamine (PDA) cogrowth chrysanthemum-like blackbody was prepared as the quenching probe to reduce the background signal. This probe combined the excellent properties of Au nanoparticles with PDA. Thus, its fluorescence quenching constant was higher than that of single Au and PDA nanoparticles by 25.8- and 4.9-fold, respectively. Furthermore, an aggregation-induced emission fluorescence microsphere with a 5.7-fold higher relative quantum yield than a commercial fluorescence microsphere was selected as the signal output carrier to improve the signal-to-noise ratio. The integration of the above triple strategies established a 53.4-fold sensitivity-enhanced fluorescence quenching ICA (LOD = 0.9 pg/mL) for detecting AFM1 in milk, providing a strong technical guarantee for the safety monitoring of milk products. [Display omitted] • APCB was prepared and first used as a highly efficient quenching probe in FQICA. • APCB combing the excellent property of both Au with PDA, has superior fluorescence quenching ability. • The mathematical relationship between K and ε of nanoquencher was first established. • The effect of the FM in FQICA on antigen-antibody binding was first explored. • The integration of triple strategies realized a 53.4-fold sensitivity-enhanced FQICA. [ABSTRACT FROM AUTHOR]

The origin and dissemination of silk have been hotly debated in the field of archaeology, and the key to resolving this controversy lies in the detection and species identification of ancient silk microtraces. Herein, a taxonomically specific anti-fibroin monoclonal antibody was successfully prepared and a layer-by-layer self assembly electrochemical immunosensor was innovatively proposed for detecting silk traces based on flexible carbon cloth. The immunosensor possessed a broad linear range of 10−2-103 ng mL−1 and a detection limit of 2.15 pg mL−1 for the ultrasensitive detection of Bombyx mori silk traces. In addition, the elaborate immunosensor exhibited satisfactory high specificity, storage stability and reproducibility. In particular, the qualitative and quantitative performance of the immunosensor was excellent in the analysis of archaeological samples. Therefore, this work demonstrates that the proposed method not only provides a reliable analytical tool for exploring the origin and spread of archaeological silk, but also improves our understanding of how to use emerging materials like two-dimensional titanium carbide to creat innovative biosensors. [ABSTRACT FROM AUTHOR]

To achieve reliable and ultrasensitive detection for disease markers in PEC bioanalysis, constructing and nano-engineering of ideal photoelectrodes and signal transduction strategies are of vital importance. Herein, a non-/noble metal coupled plasmonic nanostructure (TiO 2 /r-STO/Au) was tactically designed with high-efficient PEC performance. Evidenced by the DFT and FDTD calculations, the reduced SrTiO 3 (r-STO) was found to support the localized surface plasmon resonance due to the sufficiently increased and delocalized local charge in r-STO. Under the synergistic coupling of plasmonic r-STO and AuNPs, the PEC performance of TiO 2 /r-STO/Au was found remarkably promoted with reduced onset potential. This merit supported TiO 2 /r-STO/Au as a self-powered immunoassay via a proposed oxygen-evolution-reaction mediated signal transduction strategy. With the increase of the target biomolecules (PSA), the catalytic active sites of TiO 2 /r-STO/Au would be blocked and result in the decrease of the oxygen evaluation reaction. Under optimal conditions, the immunoassays exhibited an excellent detection performance with a LOD as low as 1.1 fg/mL. This work proposed a new type of plasmonic nanomaterial for ultrasensitive PEC bioanalysis. [Display omitted] • A non-/noble metal coupled plasmonic photoelectrode (TiO 2 /r-STO/Au) was designed. • A self-powered immunoassay via an OER-mediated signal transduction strategy was developed. • An ultrasensitive detection performance was achieved for PSA detection. [ABSTRACT FROM AUTHOR]

The early detection of very low bacterial concentrations is key to minimize the healthcare and safety issues associated with microbial infections, food poisoning or water pollution. In amperometric integrated circuits for electrochemical sensors, flicker noise is still the main bottleneck to achieve ultrasensitive detection with small footprint, cost-effective and ultra-low power instrumentation. Current strategies rely on autozeroing or chopper stabilization causing negative impacts on chip size and power consumption. This work presents a 27-μW potentiostatic-amperometric Delta-Sigma modulator able to cancel its own flicker noise and provide a 4-fold improvement in the limit of detection. The 2.3-mm2 all-in-one CMOS integrated circuit is glued to an inkjet-printed electrochemical sensor. Measurements show that the limit of detection is 15 pA rms , the extended dynamic range reaches 110 dB and linearity is R2 = 0.998. The disposable device is able to detect, in less than 1h, live bacterial concentrations as low as 102 CFU/mL from a 50-μL droplet sample, which is equivalent to 5 microorganisms. [ABSTRACT FROM AUTHOR]

[Display omitted] • The regulable amphiphilic peptide nanofibers achieved signal amplification. • The CQDs@MIL-101 was developed to provide a reference signal. • Dual signal output mode endowed efficient and accurate detection performance. • The limit of detection reduced 30 times after signal amplification. • This platform had high accuracy in the detection of clinical samples. It is of great significance for the early diagnosis of cancer to detect the tumor biomarkers in human blood. However, it is still challenging to develop easily available and cost-effective methods to detect the ultralow-level tumor biomarkers. In this work, an innovative signal amplification strategy was developed for the ultrasensitive detection of tumor biomarkers. Amphiphilic peptides with high self-assembly performance can self-assemble into regulable nanofibers and enrich fluorophore to amplify the signal, which can improve the sensitivity of detection. Meanwhile, the design of MOFs with higher fluorescence quenching efficiency and luminescence characteristics can realize double-signal output and further improve the accuracy and sensitivity of detection. Taking alpha-fetoprotein (AFP) as a model tumor biomarker, this strategy achieved a wide linear range of 1–40 ng/mL detection, reducing the limit of detection (LOD) from 9.02 ng/mL to 0.28 ng/mL compared with no signal amplification strategy. Significantly, the results of clinical samples detected by this strategy was consistent with chemiluminescence immunoassay used in clinical practice. Our work provides a brand-new idea for signal amplification strategy and shows an important application prospect in the early diagnosis of various diseases. [ABSTRACT FROM AUTHOR]

[Display omitted] • Ultrasensitive detection is critical for investigating silk's origin and spread. • A dual-responsive PEC immunosensor was prepared for silk microtrace detection. • The sensor was developed by in-situ growth of Ag 2 S on ZnO-MXene nanocomposites. • The sensor exhibits excellent taxonomic specificity, repeatability and stability. • The dual-responsive PEC immunosensor is applied for detection of real silk samples. Developing an effective analytical method for microtrace detection of ancient silk is highly desirable and vitally crucial for exploring the origin and spread of silk. Herein, a taxonomically specific anti-fibroin monoclonal antibody was prepared and an elaborate visible/near-infrared (vis/NIR) photoelectrochemical (PEC) immunosensor was proposed. The sensor employed Ag 2 S nanoparticles (NPs) grown in situ on ZnO nanowire array-MXene nanocomposites (ZnO-MX) via a sonochemical method as a photosensitive material. The experimental results illustrated that the ZnO-MX/Ag 2 S-based sensor presented 6.8 times larger PEC responses than a ZnO-MX-based sensor under visible light illumination, and the PEC signal of the ZnO-MX/Ag 2 S nanocomposites was 30 times as high as that of ZnO-MX under 808 nm NIR light, indicating enhanced photoelectric activity and a matched energy band structure of ZnO with MXene and Ag 2 S. This PEC immunosensor exhibited excellent potential for the ultrasensitive detection of Bombyx mori silk traces due to its wide linear range of 0.005–50 ng mL−1 and low detection limit of 1.51 pg mL−1. Additionally, the immunosensor showed outstanding specificity, stability, and repeatability, particularly for the qualitative detection of archeological artifacts. Given its aforementioned benefits, ZnO-MX/Ag 2 S nanocomposites are potentially attractive photoactive materials for use in vis/NIR PEC immunosensors. Moreover, this demonstrated method offers a feasible method to investigate the history and distribution of ancient silk. [ABSTRACT FROM AUTHOR]

Food safety is one of the greatest public health challenges. Developing ultrasensitive detection methods for analytes at ultra-trace levels is, therefore, essential. In recent years, the bio-barcode assay (BCA) has emerged as an effective ultrasensitive detection strategy that is based on the indirect amplification of various DNA probes. This review systematically summarizes the progress of fluorescence, PCR, and colorimetry-based BCA methods for the detection of various contaminants, including pathogenic bacteria, toxins, pesticides, antibiotics, and other chemical substances in food in over 120 research papers. Current challenges, including long experimental times and strict storage conditions, and the prospects for the application of BCA in biomedicine and environmental analyses, have also been discussed herein. [Display omitted] • Bio-barcode assay (BCA) is a novel rapid detection technology. • BCA has several advantages over conventional methods. • We summarize the concept and detection principles of BCA. • BCA has extensive applications in food testing. [ABSTRACT FROM AUTHOR]

p53 is a powerful transcription factor playing a pivotal role in the prevention of cancer development and in maintaining genome integrity. This oncosuppressor is found to be functionally inactivated by mutations in many human tumors. Accordingly, wild type p53 and its oncogenic mutants represent valuable cancer biomarkers for diagnostic and prognostic purposes. We developed a highly sensitive biosensor, based on Surface Enhanced Raman Spectroscopy, for detection of wild type p53 and of p53 R175H , which is one of the most frequent tumor-associated mutants of p53. Our approach combines the huge Raman signal enhancement, mainly arising from the plasmonic resonance effect on molecules close to gold nanoparticles, with the antigen-antibody biorecognition specificity. By following the enhanced signal of a specific Raman marker, intrinsic to the nanoparticle-antibody bioconjugation, we were able to push the antigen detection level down to the attomolar range in buffer and to the femtomolar range in spiked human serum. The method demonstrated a high reproducibility and a remarkable selectivity in discriminating between wild type p53 and p53 R175H mutant, in both buffer and serum. A calibration plot was built and validated by ELISA for a reliable quantification of p53. These findings entitle our SERS-based immunosensor as a powerful and reliable tool for a non-invasive screening in human serum targeting p53 network. The approach could be easily extended to ultrasensitive detection of other markers of general interest, with feasible implementations into multiplex assays, functioning as lab-on-chip devices for several applications. [ABSTRACT FROM AUTHOR]

A reversible dual-channel chemosensor ( W ) based on double Schiff-base for ultrasensitive fluorescence detection of Cu 2+ in DMSO solution has been designed and synthesized. Upon the addition of Cu 2+ , the chemosensor W showed visible color changes (from yellow to colorless) and the fluorescence was immediately quenched. The fluorescence spectrum detection limit for Cu 2+ was 4.87 nM, which is much better than most reported fluorescent sensors for Cu 2+ . Interestingly, the sensing behavior was found to be reversible with addition of EDTA, which indicated that W not only could act as a nice candidate for Cu 2+ and EDTA controlled “ON-OFF-ON” fluorescence switch, but was utilized as an ultrasensitive IMPLICATION logic gate at the molecular level. More importantly, ion test strips based on W were fabricated, which could act as convenient and efficient test kits to detect Cu 2+ for “in-the-field” measurement. [ABSTRACT FROM AUTHOR]

A nanohybrid composed of Ag@Cu 2 O heterogeneous nanocrystals supported on N-doped reduced graphene oxide (Ag@Cu 2 O/N-RGO) has been synthesized by a simple wet-chemical method. The resultant composite consists of N-RGO sheets fully and homogeneously coated with a dense layer of Ag@Cu 2 O nanocrystals. Both Ag and N-RGO are in direct contact with Cu 2 O, and Ag nanoparticles with sizes of 2–5 nm are mainly deposited on the surface of Cu 2 O cubes (edge length of 500 nm). The electrochemical studies reveal that the ternary Ag@Cu 2 O/N-RGO composite exhibit significantly enhanced electrocatalytic activity for H 2 O 2 sensing compared with either the single component (N-RGO) or two component systems (Cu 2 O/N-RGO and Ag/N-RGO), which is mainly due to the synergetic catalysis of the ternary system. The nonenzymatic sensor based on Ag@Cu 2 O/N-RGO composite shows overwhelmingly superior comprehensive performance for the H 2 O 2 detection over the documented Ag-based sensors. More specifically, it displays a rapid response (10 s) to H 2 O 2 over a wide linear range of 54–700 nM with a high sensitivity of 1298.3 μA mM −1  cm −2 and a low detection limit of 10 nM. Moreover, the sensor also exhibits the preferable selectivity in the presence of biologically coactive compounds accompanied with long-term stability and good reproducibility. [ABSTRACT FROM AUTHOR]

Fluorescence nanoprobes are frequently employed to construct sensitive biosensors via turn-on and turn-off strategy. In this paper, a novel strategy for ultrasensitive detection of iodide was firstly constructed based on Ag + regulated photoluminescence enhancement of gold nanoclusters (AuNCs) as a turn-off nanoplatform. In the presence of Ag + , the fluorescence (FL) intensity of AuNCs can be enhanced obviously. When adding iodide ions (I - ) in the Ag + -AuNCs, Ag + can be pulled down from AuNCs and results in quenching of the fluorescent effectively owing to the combination between Ag + and I - . Compared with that of I - directly reaction with AuNCs, the introducing of Ag + shows improved quenching efficiency from 32% to 66% since I - can react with Ag + as well as AuNCs. Therefore, the platform could be applied to assay Ag + and I - , on the basis of the FL enhancement and the further FL quenching. The detection ranges and detection limits were 0.2–12 μM and 0.06 μM for Ag + , 0.001–6 μM and 0.3 nM for I - , respectively. The new sensing method based on ion regulation to enhance the detection sensitivity can extend to the appliance of other fluorescent materials in biosensing and biomedical field. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are closely bound up with the occurrence and deterioration of some cancers, and their early diagnoses have aroused great interest. However, stable and ultra-sensitive real-time detection remains challenge. In this work, we report a strategy for real-time ultrasensitive detection of miRNA-21 by capacitor/enzymatic biofuel cell based self-powered biosensor (EBFC-SPB) with hybridization chain reaction (HCR) for signal amplification. The nitrogen doped dodecahedral hollow carbon (N-DHC) is used for high load, exonuclease III (EXO III)-aided target cells for accurate recognition, and HCR for signal amplification. In addition, the detected signals are further enhanced by a good match with the commercial capacitor, and the real-time portable detection of tumor markers can be achieved by directly reading the data with an Android smartphone. The detection limit of the method is 0.04 fM (S/N = 3) in the linear range of 0.01–5.0 × 103 fM. This method provides reference and theoretical support for the early diagnosis of related tumor markers. • Exo III functionalizes miRNA recognition to improve accuracy. • HCR, N-DHC and BDM are introduced for signal amplification. • Integration of capacitor/EBFC-SPB and smartphone for highly stable and real-time ultra-sensitive detection. [ABSTRACT FROM AUTHOR]

• A microtrap-assisted microfluidic magnetic immunoassays (μ MI) was developed. • The microtrap assisted analyte concentration and signal amplification in μ MI. • Microtrap-assisted μ MI was provided for ultrasensitive detection of MCP-1 and MMP-9. • Microtrap-assisted μ MI was applied to analysis of biomarkers in human serum samples. Precise and accurate quantitation of important biomarkers is significant, especially in early-stage diseases diagnosis. To realized effective biosample preparation and trace-level biomarker detection, a microtrap-assisted microfluidic magnetic immunoassays (μ MI) method was developed in this work. A microtrap was fabricated inside the straight microchannel of μ MI device to help magnetic separation and concentration of immunocomplexes. These immunocomplexes were enriched in microtrap of μ MI device to accomplish selective and sensitive biomarker detection. Horseradish peroxidase-labeled magnetic beads were employed to evaluate assay feasibility and microtrap effect on assay sensitivity. The microtrap-assisted μ MI was then applied for model biomarkers detection. The limits of detection of μMI were 0.025 pg/mL for monocyte chemoattractant protein-1 (MCP-1) and 0.021 pg/mL for matrix metalloproteinase-9 (MMP-9), which corresponded up to 2014-fold sensitivity improvement compared to their standard microwell enzyme-linked immunosorbent assay (ELISA) results. In addition, the selectivity and reproducibility of microtrap-assisted μ MI were confirmed. In clinical serum sample analysis, recoveries of 91.3%-106.7% with relative standard deviations less than 6.1% were obtained for MCP-1 and MMP-9, and method accuracy was verified by commercial ELISA kit. The developed μ MI can accomplish ultratrace biomarker detection offering practical tool for laboratorial and clinical research. [Display omitted] [ABSTRACT FROM AUTHOR]

Selective and sensitive determination of ochratoxin A (OTA) is critical due to its high toxicity and wide distribution. Here, a neoteric electrochemical biosensor based on an exonuclease III (Exo III)-assisted recycling reaction triggering the trans -cleavage ability of CRISPR-Cas12a was developed, allowing the specific and ultrasensitive detection of OTA. In this strategy, the Exo III-assisted recycling reaction was used to convert and magnify the target recognition affair into the trigger DNA chain to the trans -cleavage activity of Cas12a for detecting electrochemical signal changes, thus enhancing detection sensitivity. When the Fc-ssDNA was fixed onto a glassy carbon electrode and used as a reporter probe under optimized conditions, the method showed good selectivity and sensitivity for OTA determination, and a detection limit of 0.74 fg/mL. Furthermore, the established method could sensitively identify OTA in spiked rice and peanut samples, demonstrating its application potential for practical detection. [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel diagnostic system for the rapid and ultrasensitive detection of pathogens. • Fluorescence and colorimetric systems based on light-up RNA aptamers or LFAs. • A single copy per reaction determined without cross-reactivity with other pathogens. • The one-pot system accelerates adoption in facility-limited or POC settings. An accurate, convenient, and rapid diagnostic platform, which can be applied in facility-limited or point-of-care (POC) settings, is essential to help prevent the spread of infectious diseases and enable the most effective treatment to be selected. In this study, we describe the development of a new isothermal molecular diagnostic system named m ultipurpose a dvanced s plit T7 promot er -based transcription amplification (MASTER) for the rapid and ultrasensitive detection of various pathogens containing single-stranded RNA and double-stranded DNA. MASTER produces a large number of RNA amplicons in the presence of target pathogens, which generate fluorescence or colorimetric signals based on light-up RNA aptamers or lateral flow assays. Implementing MASTER at 37 °C for<1 h achieved the detection of a single copy per reaction without cross-reactivity. Moreover, the testing of 40 clinical samples revealed that MASTER exhibited excellent accuracy with 100% sensitivity and specificity for SARS-CoV-2 diagnosis. Furthermore, a one-pot MASTER system capable of accelerating practical applications was demonstrated, indicating that the MASTER system is a promising platform for the effective surveillance of various pathogens. [ABSTRACT FROM AUTHOR]

Sensitive and accurate determination of tumor-derived exosomes from complicated biofluids is an important prerequisite for early tumor diagnosis through exosome-based liquid biopsy. Herein, a label-free fluorescence immunoassay protocol for ultrasensitive detection of exosomes was developed by engineering substantial dimerized guanine-quadruplex (Dimer-G4) signal units via in situ cutting-mediated exponential rolling circle amplification (CM-ERCA). First, exosomes were captured and enriched via immunomagnetic separation. Then, molecular recognition was built by the formation of antibody−aptamer sandwich immunocomplex through the specific binding of the designed aptamer-primers with the targeted exosomes. The accuracy of exosome detection was significantly improved by the specific recognition of two typical exosomal protein markers simultaneously. Eventually, in situ CM-ERCA was triggered by a perfect match between the multifunctional circular DNA template and the aptamer-primer on exosomal surface. Amplicons of CM-ERCA loaded with Dimer-G4 were exponentially accumulated during continuous cyclic amplification, dramatically lighting up the thioflavin T (ThT) and generating substantial Dimer-G4 signal units. As a result, ultrasensitive detection of exosomes with the detection limit down to 2.4 × 102 particles/mL was achieved due to the fluorescence enhancement of substantial Dimer-G4 signal units, which is ahead of most of available fluorescence-based methods reported currently. In addition, the intense fluorescence emission and favorable anti-interference of the proposed immunoassay supports identification of exosomes direct in human serums, overcoming the limitations of conventional G4/ThT in serum analysis and revealing its potential for exosome-based liquid biopsy. [Display omitted] • Dimer-G4/ThT was exploited as a high-efficiency "light-up" indicator for sensing exosomes. • Substantial Dimer-G4 signal units with intense fluorescence were engineered. • Realizing ultrasensitive detection of exosomes with a LOD of 2.4 × 102 particles/mL. • Achieving label-free and high specific analysis of exosomes directly in human serums. [ABSTRACT FROM AUTHOR]