Kiwi-Inspired Rational Nanoarchitecture with Intensified and Discrete Magneto-Fluorescent Functionalities for Ultrasensitive Point-of-Care Immunoassay.

Fluorescent lateral flow immunoassays (FLFIA) is a well-established rapid detection technique for quantitative analysis. However, achieving accurate analysis of biomarkers at the pg mL-1 level using FLFIA still poses challenges. Herein, an ultrasensitive FLFIA platform is reported utilizing a kiwi-type magneto-fluorescent silica nanohybrid (designated as MFS) that serves as both a target-enrichment substrate and an optical signal enhancement label. The spatially-layered architecture comprises a Fe3O4 core, an endocarp-fibers like dendritic mesoporous silica, seed-like quantum dots, and a kiwi-flesh like silica matrix. The MFS demonstrates heightened fluorescence brightness, swift magnetic response, excellent size uniformity, and dispersibility in water. Through liquid-phase capturing and fluorescence-enhanced signal amplification, as well as magnetic-enrichment sample amplification and magnetic-separation noise reduction, the MFS-based FLFIA is successfully applied to the detection of cardiac troponin I that achieved a limit of detection at 8.4 pg mL-1, tens of times lower than those of previously published fluorescent and colorimetric lateral flow immunoassays. This work offers insights into the strategic design of magneto-fluorescent synergetic signal amplification on LFIA platform and underscores their prospects in high-sensitive rapid and on-site diagnosis of biomarkers.

Control of mitochondrial dynamics and apoptotic pathways by peroxisomes.

Peroxisomes are organelles containing different enzymes that catalyze various metabolic pathways such as ß-oxidation of very long-chain fatty acids and synthesis of plasmalogens. Peroxisome biogenesis is controlled by a family of proteins called peroxins, which are required for peroxisomal membrane formation, matrix protein transport, and division. Mutations of peroxins cause metabolic disorders called peroxisomal biogenesis disorders, among which Zellweger syndrome (ZS) is the most severe. Although patients with ZS exhibit severe pathology in multiple organs such as the liver, kidney, brain, muscle, and bone, the pathogenesis remains largely unknown. Recent findings indicate that peroxisomes regulate intrinsic apoptotic pathways and upstream fission-fusion processes, disruption of which causes multiple organ dysfunctions reminiscent of ZS. In this review, we summarize recent findings about peroxisome-mediated regulation of mitochondrial morphology and its possible relationship with the pathogenesis of ZS.

Hue Recognition Competitive Fluorescent Lateral Flow Immunoassay for Aflatoxin M1 Detection with Improved Visual and Quantitative Performance.

Immunological detection of small molecules in a point-of-care (POC) format is of great significance yet remains challenging for accurate visual discrimination and quantitative analysis. Here, we report a novel hue recognition competitive fluorescent lateral flow immunoassay (HCLFIA) strip that allows both visual and quantitative detection of aflatoxin M1 (AFM1). The HCLFIA strip works on the basis of the ratiometric change of emission, arising from the overlap of fluorescence signals of two nanocomposites tagged with probe antibodies and coated antigens. A visually discernible orange-red-to-green fluorescence color change allows the naked eye semiquantitative readout of AFM1 around the threshold concentration (0.05 ng mL-1), yielding a visible detection limit of 0.02 ng mL-1. Moreover, using a custom smartphone-based device and color chart analysis, ultrasensitive quantitative detection of AFM1 can be achieved with a low limit of detection at 0.0012 ng mL-1, which is considerably better than those of the previously reported colorimetric and fluorescent strips. The accuracy performed in spiked milk samples ranged from 97.91 to 113.12% with a coefficient of variation below 7.8%, showing good consistency with the results from isotope dilution liquid chromatography-tandem mass spectrometry. Thanks to the unique hue recognition scheme, the HCLFIA strip holds great potential for POC detection of small molecules.

Ultrasensitive Competitive Lateral Flow Immunoassay with Visual Semiquantitative Inspection and Flexible Quantification Capabilities.

Antibiotics abuse has caused various problems threatening human health and ecological environment. Monitoring antibiotics residual levels is of great significance, yet still challenging for quantitative point-of-need testing with high-sensitivity and visual capability. Here we developed a competitive lateral flow immunoassay (CLFIA) platform with flexible readout for enrofloxacin (ENR), a regularly added antibiotic. To overcome the limitation of low sensitivity of traditional colloidal gold-based CLFIA, the three-dimensionally assembled gold nanoparticles (AuNPs) within dendritic silica scaffold were fabricated as signal reporters. The assembly structure effectively retained the intrinsic absorption features of hydrophobic AuNPs and greatly enhanced the light extinction ability of a single label for signal amplification. The obtained CLFIA strips can not only achieve qualitative screening of ENR at a very low concentration by naked eye (cutoff value: 0.125 ng/mL), but also enable ultrasensitive quantification of ENR by an optical scanner (limit of detection: 0.00195 ng/mL) or a smartphone (limit of detection: 0.0078 ng/mL). Moreover, to elaborate the visual inspection degree of CLFIA against traditional yes/no interpretation, a novel multirange gradient CLFIA strip was prepared for visually semiquantitative identification of ENR with four concentration ranges. The novel CLFIA platform demonstrated sensitive, specific, and reliable determination of ENR with flexible signal readout and provides a potential and invigorating pathway to point-of-need immunoassay of antibiotics.

Atomic cerium modulated palladium nanoclusters exsolved ferrite catalysts for lean methane conversion.

The active and stable palladium (Pd) based catalysts for CH4 conversion are of great environmental and industrial significance. Herein, we employed N2 as an optimal activation agent to develop a Pd nanocluster exsolved Ce-incorporated perovskite ferrite catalyst toward lean methane oxidation. Replacing the traditional initiator of H2, the N2 was found as an effective driving force to selectively touch off the surface exsolution of Pd nanocluster from perovskite framework without deteriorating the overall material robustness. The catalyst showed an outstanding T50 (temperature of 50% conversion) plummeting down to 350°C, outperforming the pristine and H2-activated counterparts. Further, the combined theoretical and experimental results also deciphered the crucial role that the atomically dispersed Ce ions played in both construction of active sites and CH4 conversion. The isolated Ce located at the A-site of perovskite framework facilitated the thermodynamic and kinetics of the Pd exsolution process, lowering its formation temperature and promoting its quantity. Moreover, the incorporation of Ce lowered the energy barrier for cleavage of C─H bond, and was dedicated to the preservation of highly reactive PdOx moieties during stability measurement. This work successfully ventures uncharted territory of in situ exsolution to provide a new design thinking for a highly performed catalytic interface.

Quantum dots assembly enhanced and dual-antigen sandwich structured lateral flow immunoassay of SARS-CoV-2 antibody with simultaneously high sensitivity and specificity.

Exploring reliable and highly-sensitive SARS-CoV-2 antibody diagnosis by point-of-care (POC) manner, holds great public health significance for extensive COVID-19 screening and controlling. Unfortunately, the currently applied gold based lateral flow immunoassay (GLFIA) may expose both false-negative and false-positive interpretations owing to the sensitivity and specificity limitations, which may cause significant risk and waste of public resources for large population screening. To simultaneously overcome the drawbacks of GLFIA, a novel fluorescent LFIA based on signal amplification and dual-antigen sandwich structure was established with largely improved sensitivity and specificity. The compact three-dimensional incorporation of hydrophobic quantum dots within dendritic affinity templates and multilayer surface derivation guaranteed a high and robust fluorescence of single label, which lowered the false negative rate of GLFIA prominently. A dual-antigen sandwich structure using labeled/immobilized SARS-CoV-2 spike receptor binding domain antigen for capturing total human SARS-CoV-2 antibody was developed, instead of general indirect antibody capturing approach, to reduce the false positive rate of GLFIA. Over 300 cases of COVID-19 negative and 97 cases of COVID-19 positive samples, the current assay revealed a 100% sensitivity and 100% specificity confirmed by both polymerase chain reaction (PCR) and chemiluminescence immunoassay (CLIA), compared with the considerable misinterpretation cases by currently applied GLFIA. The quantitative results verified by receiver operating characteristic curve and other statistical analysis indicated a well-distinguished positive/negative sample groups. The proposed strategy is highly sensitive towards low concentrated SARS-CoV-2 antibody serums and highly specific towards serums from COVID-19 negative persons and patients infected by other viruses.

Compact Magneto-Fluorescent Colloids by Hierarchical Assembly of Dual-Components in Radial Channels for Sensitive Point-of-Care Immunoassay.

Exploring signal amplification strategies to enhance the sensitivity of lateral flow immunoassay (LFIA) is of great significance for point-of-care (POC) testing of low-concentrated targets in the field of in vitro diagnostics. Here, a highly-sensitive LFIA platform using compact and hierarchical magneto-fluorescent assemblies as both target-enrichment substrates and optical sensing labels is demonstrated. The large-pored dendritic templates are utilized for high-density incorporation of both superparamagnetic iron oxide nanoparticles (IOs) and quantum dots (QDs) within the vertical channels. The hierarchical structure is built via affinity-driven assembly of IOs and QDs from organic phase with silica surface and mercapto-organosilica intermediate layer, respectively. The sequential assembly with central-radial channels enables 3D loading of dual components and separately controlling of discrete functionalities. After the alkyl-organosilica encapsulation and silica sealing, the composite spheres exhibit high stabilities and compatibility with LFIA for procalcitonin (PCT) detection. With the assistance of liquid-phase antigen-capturing, magnetic enrichment, and fluorescence-signal amplification, a limit of detection of 0.031 ng mL-1 for PCT is achieved with a linear range from 0.012 to 10 ng mL-1 . The current LFIA is robust and validated for PCT detection in real serum, which holds great diagnostic significance for precise guidance of antibiotic therapy with POC manner.

Ratiometric Fluorescent Lateral Flow Immunoassay for Point-of-Care Testing of Acute Myocardial Infarction.

We report the development of a highly sensitive ratiometric fluorescent lateral flow immunoassay (RFLFIA) strip for rapid and accurate detection of acute myocardial infarction biomarker, namely heart-type fatty acid binding protein (H-FABP). The RFLFIA strip works in terms of ratiometric change of fluorescence signal, arising from blending of fluorescence emitted by two composite nanostructures conjugated to capture and probe antibodies and inner filter effect of gold nanoparticles. In conjunction with using custom smartphone-based analytical device and tonality analysis, quantitative detection of H-FABP was achieved with a low limit of detection at 0.21 ng mL-1 . The RFLFIA strip can generate a visually distinguishable green-to-red color change around the threshold concentration of H-FABP (6.2 ng mL-1 ), thus allowing the semi-quantitative diagnosis by the naked eye.

Hierarchical Plasmonic-Fluorescent Labels for Highly Sensitive Lateral Flow Immunoassay with Flexible Dual-Modal Switching.

Lateral flow immunoassay (LFIA), as a prominent point-of-care (POC) test platform, has been extensively adopted for rapid, on-site, and facile diagnosis of pathogen infections and disease biomarkers. Exploring novel structured optical labels of LFIA with amplified signal and complementary detection modes favors the sensitive and flexible POC diagnosis. Here, bimodal labels with both colorimetric and fluorescent readout were fabricated via a layered sequential assembly strategy based on affinity templates and hydrophobic metal-containing nanounits. High-quality colorimetric and fluorescent nanoparticles were densely incorporated into the colloidal supports and confined in separated regions, without interfering with each other. The hierarchical integration of gold nanoparticles and quantum dots with high loading density and good optical preservation realized dual readout and amplified signals from the assemblies of individual single nanoparticles. The "all-in-one" optical labels allowed both colorimetric and fluorescent detection of cystatin C (Cys C) after surface conjugation with antibodies. The LFIA strips revealed noninterfering dual signals for both visual inspection and quantitative detection of Cys C via the naked eye and portable devices, respectively. The limits of detection by colorimetric and fluorescent modes were 0.61 and 0.24 ng mL-1, respectively. The novel LFIA platform demonstrated sensitive, specific, and reproducible POC testing of biomarkers with flexible detection modes and was reliable for clinical diagnosis.

Controllable and robust dual-emissive quantum dot nanohybrids as inner filter-based ratiometric probes for visualizable melamine detection.

The ratiometric fluorescence technique is of great interest due to its visualization characteristics. The construction of a reliable fluorescent ratiometric nanoprobe for high-sensitivity visual quantification is highly sought after but it is limited by poor stability and controllability. Herein, we report a robust dual-emissive quantum dot nanohybrid with precise color tunability and demonstrate its potential as a two-signal-change ratiometric probe for visual detection. A novel assembly strategy was developed for spatially implanting hydrophobic green and red quantum dots (QDs) into a silica scaffold to form a dual-emissive hierarchical fluorescent silica nanohybrid. The fluorescence intensity ratio and color of the nanohybrid were precisely tailored by altering the amounts of green and red QDs. Particularly, after the alkylsilane-mediated phase transfer and exterior silica shell growth, the nanohybrid exhibited the well-preserved fluorescence features of the original QDs and robust optical/colloid stability. An inner filter-based ratiometric nanoprobe for the visual determination of melamine was ultimately devised by combining the spectra-overlapped two-colored fluorescent nanohybrid with analyte-specific gold nanoparticles. Furthermore, based on the reversible fluorescence signal changes in two-colored QDs induced by melamine, a logic gate strategy for melamine monitoring was constructed. The newly developed fluorescent ratiometric nanoprobe shows great prospects for the visual and quantitative determination of analytes in a complex biological matrix.

Ratiometric fluorometric and visual determination of cyanide based on the use of carbon dots and gold nanoclusters.

An optical method is described for the ratiometric fluorometric determination of cyanide ions. It is based on the use of a mixture of aqueous solutions of blue-emitting carbon dots (CDs) and red-emitting gold nanoclusters (AuNCs). The presence of cyanide reduces the red fluorescence of the AuNCs through the formation of a stable complex [Au(CN)2-]. The blue emission of the CDs, in contrast, stays constant. Hence, the color of fluorescence changes from red to purple to blue. The ratio of the fluorescence intensities located at 612 and 438 nm varies over a wide range, with 2 linear responses ranges (from 8 nM to 12.5 µM, and from 12.5 to 75 µM). The method was applied to the determination and visual discrimination of cyanide in food and drink samples. Graphical abstract A ratiometric method for determination of cyanide detection is described that is based on mixing carbon dots (CDs) and gold nanoclusters (AuCNs). The presence of cyanide reduces the red fluorescence of the AuNCs through the formation of a stable complex Au(CN)2-. The blue emission of the CDs, in contrast, stays constant. The fluorescence intensity ratios show linear response to cyanide with a concomitant red-purple-blue fluorescence color change.

Homogeneous and high-density gold unit implanted optical labels for robust and sensitive point-of-care drug detection.

Controllable integration of gold building blocks into mesoscopic architecture produces improved optical signals with preferable stability for biological sensing. Here, we developed novel optical labels with homogeneous and high-density implanted hydrophobic gold nanoparticles (AuNPs) throughout three-dimensional silica scaffolds. The dendritic silica supports with an extra-large pore size and highly accessible central-radial channels were employed as metal-affinity templates, for anchoring with AuNPs directly from the organic phase. The nano-assemblies exhibited a high unit loading capacity while maintaining the intrinsic optical characteristics of AuNPs. After phase transfer by the alkylsilane intermediate layer and exterior silica shell encapsulation, the nanocomposites revealed an amplified plasmonic absorption signal, excellent colloidal/optical stability and convenient surface functionalization. By integrating the silica labels into the lateral flow immunoassay strip for signal enhancement, the sensitive point-of-care detection of methamphetamine in urine was established. The limit of detection achieved 0.026 ng mL-1, with a detection range from 0.023 to 375 ng mL-1 in a 10 min assay, allows both visual and on-site quantitative analysis. Encouragingly, the potential interfering drugs in the sample matrix showed a negligible influence on the results, validating the superior specificity of the current immunoassay. The newly developed gold-implanted optical labels show prospects for point-of-care testing in a complex biological matrix with the desirable stability and signal amplification.

Establishment of the Detailed Breast Model of Chinese Adult Female and Application in External Radiation Protection.

Breast is one of the most sensitive organs to radiation. In 2007, International Commission on Radiological Protection (ICRP) increased the tissue weighting factor for the breast from 0.05 to 0.12, which made the accurate evaluation of breast dose more important. But in the existing human voxel phantom, the structure of breast is not elaborate enough because of the limitation of image resolution used for phantom modeling. This will probably affect the accuracy of breast dose calculated in simulation. Some researches on detailed breast modeling have been carried out, but there is no such research in this field in China. A detailed breast model for Chinese adult female is established in this article using the mathematical modeling method. It is voxelized and merged with the Chinese reference adult female voxel model for breast dosimetry. Dose conversion coefficients of breast gland for external photon exposures in antero-posterior geometry are calculated as an example of the application and the results are compared with those calculated by the old voxel phantom and ICRP reference adult female voxel phantom.

Fabrication of an "ion-imprinting" dual-emission quantum dot nanohybrid for selective fluorescence turn-on and ratiometric detection of cadmium ions.

In this work, we have fabricated a new dual-emission quantum dot (QD) nanohybrid for fluorescence ratiometric determination of cadmium ions (Cd2+) in water samples, where the "turn-on" model and "ion-imprinting" technique were incorporated simultaneously. The nanohybrid probe was composed of green-emitting CdSe QDs covalently linked onto the surface of silica nanoparticles embedded with red-emitting CdTe QDs. The chemical etching of ethylene diamine tetraacetic acid (EDTA) at the surface produced specific Cd2+ recognition sites and quenched the green fluorescence of outer CdSe QDs. Upon exposure to different amounts of Cd2+, the green fluorescence was gradually restored, whereas the inner red fluorescence remained constant. As a consequence, an obviously distinguishable fluorescence color variation (from red to green) of the probe solution was observed. Under the optimized conditions, the developed ratiometric sensor displayed a linear response range from 0.1 to 9 µM with a detection limit of 25 nM (S/N = 3) for Cd2+, which could offer an alternative sensing approach for the highly sensitive and selective detection of heavy metal ions.