Visual and Rapid Detection of Nerve Agent Mimics in Gas and Solution Phase by a Simple Fluorescent Probe.

Chemical nerve agents are highly toxic organophosphorus compounds that are easy to obtain and can be utilized by terrorists to threaten homeland security and human safety. Those organophosphorus nerve agents contain nucleophilic ability that can react with acetylcholinesterase leading to muscular paralysis and human death. Therefore, there is great importance to explore a reliable and simple method to detect chemical nerve agents. Herein, the o-phenylenediamine-linked dansyl chloride as a colorimetric and fluorescent probe has been prepared to detect specific chemical nerve agent stimulants in the solution and vapor phase. The o-phenylenediamine unit serves as a detection site that can react with diethyl chlorophosphate (DCP) in a rapid response within 2 min. A satisfied relationship line was obtained between fluorescent intensity and the concentration of DCP in the range of 0-90 µM. In the optimized conditions, we conducted the fluorescent titration to measure the limits of detection (0.082 µM) with the fluorescent enhancement up to 18-fold. Fluorescence titration and NMR studies were also conducted to explore the detection mechanism, indicating that the formation of phosphate ester causes the intensity of fluorescent change during the PET process. Finally, probe 1 coated with the paper test is utilized to detect DCP vapor and solution by the naked eye. We expect that this probe may give some admiration to design the small molecule organic probe and applied in the selectivity detection of chemical nerve agents.

Electrical performance of monolayer MoS2transistor with MoS2nanobelt metallic edges as electrodes.

The contact electrodes have great influence on the performance of monolayer MoS2devices. In this paper, monolayer MoS2and MoS2nanobelts were synthesized on SiO2/Si substrates via the chemical vapor deposition method. By using wet and dry transfer process, MoS2nanobelt metallic edges were designed as the source/drain contact electrodes of monolayer MoS2field effect transistor. The 'nanobelt metallic edges' refers to the top surface of the nanobelt being metallic. Because the base planes of MoS2nanobelt vertically stand on the substrate, which makes the layer edges form the top surface of the nanobelt. The nonlinearIds-Vdscharacteristics of the device indicates that the contact between the monolayer MoS2and MoS2metallic edges displays a Schottky-like behavior. The back-gated transfer characteristics indicate that monolayer MoS2device with MoS2nanobelt metallic edges as electrodes shows an n-type behavior with a mobility of ∼0.44 cm2V-1·s-1, a carrier concentration of ∼7.31 × 1011cm-2, and an on/off ratio of ∼103. The results enrich the electrode materials of two-dimensional material devices and exhibit potential for future application of MoS2metallic edges in electronic devices.

Improved phase stability of the CsPbI3 perovskite via organic cation doping.

We have studied the effect of organic cation doping with dimethylammonium (DMA+), ethylammonium (EA+), and guanidinium (GA+) on the properties of the CsPbI3 perovskite by performing first-principles calculations. It was found that these dopants, especially DMA+, can significantly improve the phase stability of the desired α phase of CsPbI3 by compressing the transition temperature between the photoactive α phase (cubic perovskite structure) and the photoinactive δ phase (orthorhombic structure). However, the incorporation of organic cations decreases the absorption coefficient of the CsPbI3 perovskite in the visible spectrum. The details of the improvement of the phase stability and the degradation of the optical properties arising from the organic dopants are revealed. Our results are valuable for developing stable and high performance hybrid perovskite photovoltaic materials.

Effect of cation replacement on the phase stability of formamidinium lead iodide perovskite.

First-principles calculations have been performed to study the effect of cation replacement with methylammonium (MA+), Cs+, and Rb+ on the properties of formamidinium lead iodide (FAPbI3) perovskite. It is found that these dopants could improve the stability of the desired α phase of FAPbI3 at reduced temperature by lowering the transition temperature between the perovskite cubic α phase and nonperovskite hexagonal δ phase. Interestingly, the optical absorption properties and the effective masses of holes of FAPbI3 perovskite are only slightly affected. The nature of the improvement of the phase stability resulting from the cation replacement is revealed. However, the calculated mixing energies indicate that these multication materials still suffer long-term instability. Our results provide theoretical guidance for improving current multication engineering strategies or even developing new approaches.

Membrane-Penetrating Carbon Quantum Dots for Imaging Nucleic Acid Structures in Live Organisms.

The dynamics of DNA and RNA structures in live cells are important for understanding cell behaviors, such as transcription activity, protein expression, cell apoptosis, and hereditary disease, but are challenging to monitor in live organisms in real time. The difficulty is largely due to the lack of photostable imaging probes that can distinguish between DNA and RNA, and more importantly, are capable of crossing multiple membrane barriers ranging from the cell/organelle to the tissue/organ level. We report the discovery of a cationic carbon quantum dot (cQD) probe that emits spectrally distinguishable fluorescence upon binding with double-stranded DNA and single-stranded RNA in live cells, thereby enabling real-time monitoring of DNA and RNA localization and motion. A surprising finding is that the probe can penetrate through various types of biological barriers in vitro and in vivo. Combined with standard and super-resolution microscopy, photostable cQDs allow time-lapse imaging of chromatin and nucleoli during cell division and Caenorhabditis elegans (C. elegans) growth.

Dynamic mapping of spontaneously produced H2S in the entire cell space and in live animals using a rationally designed molecular switch.

Hydrogen sulfide (H2S) is a key signaling molecule in the cytoprotection, vascular mediation and neurotransmission of living organisms. In-depth understanding of its production, trafficking, and transformation in cells is very important in the way H2S mediates cellular signal transductions and organism functions; it also motivates the development of H2S probes and imaging technologies. A fundamental challenge, however, is how to engineer probes with sensitivity and cellular penetrability that allow detection of spontaneous production of H2S in the entire cell space and live animals. Here, we report a rationally designed molecular switch capable of accessing all intracellular compartments, including the nucleus, lysosomes and mitochondria, for H2S detection. Our probe comprised three functional domains (H2S sensing, fluorescence, and biomembrane penetration), could enter almost all cell types readily, and exhibit a rapid and ultrasensitive response to H2S (≤120-fold fluorescence enhancement) for the dynamic mapping of spontaneously produced H2S as well as its distribution in the whole cell. In particular, the probe traversed blood/tissue/cell barriers to achieve mapping of endogenous H2S in metabolic organs of a live Danio rerio (zebrafish). These results open-up exciting opportunities to investigate H2S physiology and H2S-related diseases.

A dual-colored ratiometric-fluorescent oligonucleotide probe for the detection of human telomerase RNA in cell extracts.

Human telomerase RNA (hTR), which is one component of telomerase, was deemed to be a biomarker to monitor tumor cells due to its different expression levels in tumor cells and normal somatic cells. Thus far, plentiful fluorescent probes have been designed to investigate nucleic acids. However, most of them are limited since they are time-consuming, require professional operators and even result in false positive signals in the cellular environment. Herein, we report a dual-colored ratiometric-fluorescent oligonucleotide probe to achieve the reliable detection of human telomerase RNA in cell extracts. The probe is constructed using a dual-labeled fluorescent oligonucleotide hybridized with target-complemented Dabcyl-labeled oligonucleotide. In the presence of the target, the dual-labeled fluorescent oligonucleotide translates into a hairpin structure, which leads to the generation of the fluorescence resonance energy transfer (FRET) phenomenon under UV excitation. Compared to conventional methods, this strategy could effectively avoid false positive signals, and it not only possesses the advantages of simplicity and high specificity but also has the merits of signal stability and distinguishable color variation. Moreover, the quantitative assay of hTR would have a far-reaching impact on the telomerase mechanism and even tumor diagnosis research.

Real-Time Discrimination and Versatile Profiling of Spontaneous Reactive Oxygen Species in Living Organisms with a Single Fluorescent Probe.

Fluorescent probes are powerful tools for the investigations of reactive oxygen species (ROS) in living organisms by visualization and imaging. However, the multiparallel assays of several ROS with multiple probes are often limited by the available number of spectrally nonoverlapping chromophores together with large invasive effects and discrepant biological locations. Meanwhile, the spontaneous ROS profilings in various living organs/tissues are also limited by the penetration capability of probes across different biological barriers and the stability in reactive in vivo environments. Here, we report a single fluorescent probe to achieve the effective discrimination and profiling of hydroxyl radicals (•OH) and hypochlorous acid (HClO) in living organisms. The probe is constructed by chemically grafting an additional five-membered heterocyclic ring and a lateral triethylene glycol chain to a fluorescein mother, which does not only turn off the fluorescence of fluorescein, but also create the dual reactive sites to ROS and the penetration capability in passing through various biological barriers. The reactions of probe with •OH and HClO simultaneously result in cyan and green emissions, respectively, providing the real-time discrimination and quantitative analysis of the two ROS in cellular mitochondria. Surprisingly, the accumulation of probes in the intestine and liver of a normal-state zebrafish and the transfer pathway from intestine-to-blood-to-organ/tissue-to-kidney-to-excretion clearly present the profiling of spontaneous •OH and HClO in these metabolic organs. In particular, the stress generation of •OH at the fresh wound of zebrafish is successfully visualized for the first time, in spite of its extremely short lifetime.

Label-free surface-enhanced Raman scattering imaging to monitor the metabolism of antitumor drug 6-mercaptopurine in living cells.

The molecular processes of drugs from cellular uptake to intracellular distribution as well as the intracellular interaction with the target molecule are critically important for the development of new antitumor drugs. In this work, we have successfully developed a label-free surface-enhanced Raman scattering (SERS) technique to monitor and visualize the metabolism of antitumor drug 6-mercaptopurine in living cells. It has been clearly demonstrated that Au@Ag NPs exhibit an excellent Raman enhancement effect to both 6-mercaptopurine and its metabolic product 6-mercaptopurine-ribose. Their different ways to absorb at the surface of Au@Ag NPs lead to the obvious spectral difference for distinguishing the antitumor drug and its metabolite by SERS spectra. The Au@Ag NPs can easily pass through cell membranes in a large amount and sensitively respond to the biological conversion of 6-mercaptopurine in tumor cells. The Raman imaging can visualize the real-time distribution of 6-mercaptopurine and its biotransformation with the concentrations in tumor cells. The SERS-based method reported here is simple and efficient for the assessments of drug efficacy and the understanding of the molecular therapeutic mechanism of antitumor drugs at the cellular level.

Inkjet-printed silver nanoparticle paper detects airborne species from crystalline explosives and their ultratrace residues in open environment.

An electronic nose can detect highly volatile chemicals in foods, drugs, and environments, but it is still very much a challenge to detect the odors from crystalline compounds (e.g., solid explosives) with a low vapor pressure using the present chemosensing techniques in such way as a dog's olfactory system can do. Here, we inkjet printed silver nanoparticles (AgNPs) on cellulose paper and established a Raman spectroscopic approach to detect the odors of explosive trinitrotoluene (TNT) crystals and residues in the open environment. The layer-by-layer printed AgNP paper was modified with p-aminobenzenethiol (PABT) for efficiently collecting airborne TNT via a charge-transfer reaction and for greatly enhancing the Raman scattering of PABT by multiple spectral resonances. Thus, a Raman switch concept by the Raman readout of PABT for the detection of TNT was proposed. The AgNPs paper at different sites exhibited a highly uniform sensitivity to TNT due to the layer-by-layer printing, and the sensitive limit could reach 1.6 × 10(-17) g/cm(2) TNT. Experimentally, upon applying a beam of near-infrared low-energy laser to slightly heat (but not destruct) TNT crystals, the resulting airborne TNT in the open environment was probed at the height of 5 cm, in which the concentration of airborne species was lower than 10 ppt by a theoretical analysis. Similarly, the odors from 1.4 ppm TNT in soil and 7.2, 2.9, and 5.7 ng/cm(2) TNT on clothing, leather, and envelope, respectively, were also quickly sensed for 2 s without destoying these inspected objects.

Surface-enhanced Raman scattering chip for femtomolar detection of mercuric ion (II) by ligand exchange.

The chemical sensing for the convenient detection of mercuric ion (II) (Hg(2+)) have been widely explored with the use of various sensing materials and techniques. It still remains a challenge to achieve ultrasensitive but simple, rapid, and inexpensive detection to metal ions. Here we report a surface-enhanced Raman scattering (SERS) chip for the femtomolar (fM) detection of Hg(2+) by employing silver-coated gold nanoparticles (Au@Ag NPs) together with an organic ligand. 4,4'-Dipyridyl (Dpy) can control the aggregation of Au@Ag NPs via its dual interacting sites to Ag nanoshells to generate strong Raman hot spots and SERS readouts. However, the presence of Hg(2+) can inhibit the aggregation of Au@Ag NPs by the coordination with Dpy, and as a result the SERS signals of Dpy are quenched. On the basis of these findings, a SERS chip has been fabricated by the assembly of Au@Ag NPs on a piece of silicon wafer and the further modification with Dpy. The exchange of Dpy from the chip into the aqueous Hg(2+) droplet results in the quenching of Raman signals of Dpy, responding to 10 fM Hg(2+) that is about 6 orders of magnitude lower than the limit defined by the U.S. Environmental Protection Agency in drinkable water. Each test using the SERS chip only needs a droplet of 20 µL sample and is accomplished within ∼4 min. The SERS chip has also been applied to the quantification of Hg(2+) in milk, juice, and lake water.

Folic Acid Adjustive Polydopamine Organic Nanoparticles Based Fluorescent Probe for the Selective Detection of Mercury Ions.

Polydopamine fluorescent organic nanomaterials present unique physicochemical and biological properties, which have great potential application in bio-imaging and chemical sensors. Here, folic acid (FA) adjustive polydopamine (PDA) fluorescent organic nanoparticles (FA-PDA FONs) were prepared by a facile one-pot self-polymerization strategy using dopamine (DA) and FA as precursors under mild conditions. The as-prepared FA-PDA FONs had an average size of 1.9 ± 0.3 nm in diameter with great aqueous dispersibility, and the FA-PDA FONs solution exhibit intense blue fluorescence under 365 nm UV lamp, and the quantum yield is ~8.27%. The FA-PDA FONs could be stable in a relatively wide pH range and high ionic strength salt solution, and the fluorescence intensities are constant. More importantly, here we developed a method for rapidly selective and sensitive detection of mercury ions (Hg2+) within 10 s using FA-PDA FONs based probe, the fluorescence intensities of FA-PDA FONs presented a great linear relationship to Hg2+ concentration, the linear range and limit of detection (LOD) were 0-18 µM and 0.18 µM, respectively. Furthermore, the feasibility of the developed Hg2+ sensor was verified by determination of Hg2+ in mineral water and tap water samples with satisfactory results.

Online Quantitative Analysis of Chlorine Contents in Chlorinated Paraffins by Facile Raman Spectroscopy.

Online analysis of industrial chemicals is extremely important for managing product quality and performance. The chlorine (Cl) content is one of the most important technical metrics for chlorinated paraffins (CPs), and the conventional approaches to estimate Cl contents require transforming the Cl element to chloride followed by quantitative analysis with either titration or instrumentation, which are normally tedious and time-consuming and cannot simultaneously guide the industrial production. Here, we developed a rapid, real-time, and online approach to determine the Cl content of CPs with facile Raman spectroscopy. The chlorination of paraffins generated two new Raman peaks at 610-618 and 668-690 cm-1, which are associated with the vibrational modes of the SHH and SHC conformations of the C-Cl bond in CPs, respectively. More importantly, the corresponding peak of the SHH conformation decreased and that of the SHC conformation increased with the enhancement of the chlorination degree of CPs. The ratiometric calculation of the two respective Raman peak areas leads to a quantitative analysis of the Cl content of CPs. The developed approach can online provide the Cl contents of CPs within seconds accurately but without the tedious sample treatment required by conventional approaches. The strategy of integrating Raman analysis with the industrial pipeline will help in managing the production and quality control of industrial chemicals.

Shell thickness-dependent Raman enhancement for rapid identification and detection of pesticide residues at fruit peels.

Here, we report the shell thickness-dependent Raman enhancement of silver-coated gold nanoparticles (Au@Ag NPs) for the identification and detection of pesticide residues at various fruit peels. The Raman enhancement of Au@Ag NPs to a large family of sulfur-containing pesticides is ~2 orders of magnitude stronger than those of bare Au and Ag NPs, and there is a strong dependence of the Raman enhancement on the Ag shell thickness. It has been shown for the first time that the huge Raman enhancement is contributed by individual Au@Ag NPs rather than aggregated Au@Ag NPs with "hot spots" among the neighboring NPs. Therefore, the Au@Ag NPs with excellent individual-particle enhancement can be exploited as stand-alone-particle Raman amplifiers for the surface identification and detection of pesticide residues at various peels of fruits, such as apple, grape, mango, pear, and peach. By casting the particle sensors onto fruit peels, several types of pesticide residues (e.g., thiocarbamate and organophosphorous compounds) have been reliably/rapidly detected, for example, 1.5 nanograms of thiram per square centimeter at apple peel under the current unoptimized condition. The surface-lifting spectroscopic technique offers great practical potentials for the on-site assessment and identification of pesticide residues in agricultural products.

Molecularly imprinted shells from polymer and xerogel matrices on polystyrene colloidal spheres.

We have devised a facile and general methodology for the synthesis of various molecularly imprinted shells at the surface of polystyrene (PS) colloidal spheres to recognize the explosive compound 2,4,6-trinitrotoluene (TNT). PS spheres with surface-functionalized carboxyl-group layers could direct a selective imprinting polymerization on their surface through the hydrogen-bonding interactions between surface carboxyl groups and amino monomers. Meanwhile, homogeneous polymerization in the solution phase was completely prevented by stepwise polymerization. The overall process led to the formation of monodisperse molecularly imprinted core-shell microspheres, and was very successful in the preparation of organic polymer and inorganic xerogel shells. Furthermore, greater capacity and faster binding kinetics towards target species were achieved, because surface-imprinted sites ensured the complete removal of templates, good accessibility to target molecules, and low mass-transfer resistance. The results reported herein, concerning the production of high-quality molecularly imprinted products, could also form the basis for the formulation of a new strategy for the fabrication of various functional coating layers on colloidal spheres with potential applications in the fields of separations and chemical sensing.

Instant visual detection of trinitrotoluene particulates on various surfaces by ratiometric fluorescence of dual-emission quantum dots hybrid.

To detect trace trinitrotoluene (TNT) explosives deposited on various surfaces instantly and on-site still remains a challenge for homeland security needs against terrorism. This work demonstrates a new concept and its utility for visual detection of TNT particulates on various package materials. The concept takes advantages of the superior fluorescent properties of quantum dots (QDs) for visual signal output via ratiometric fluorescence, the feasibility of surface grafting of QDs for chemical recognition of TNT, and the ease of operation of the fingerprint lifting technique. Two differently sized CdTe QDs emitting red and green fluorescences, respectively, have been hybridized by embedding the red-emitting one in silica nanoparticles and covalently linking the green-emitting one to the silica surface, respectively, to form a dual-emissive fluorescent hybrid nanoparticle. The fluorescence of red QDs in the silica nanoparticles stays constant, whereas the green QDs functionalized with polyamine can selectively bind TNT by the formation of Meisenheimer complex, leading to the green fluorescence quenching due to resonance energy transfer. The variations of the two fluorescence intensity ratios display continuous color changes from yellow-green to red upon exposure to different amounts of TNT. By immobilization of the probes on a piece of filter paper, a fingerprint lifting technique has been innovated to visualize trace TNT particulates on various surfaces by the appearance of a different color against a yellow-green background under a UV lamp. This method shows high selectivity and sensitivity with a detection limit as low as 5 ng/mm(2) on a manila envelope and the attribute of being seen with the naked eye.

Trinitrotoluene explosive lights up ultrahigh Raman scattering of nonresonant molecule on a top-closed silver nanotube array.

The highest Raman enhancement factors are obtained in a double resonance: molecular electronic resonance and plasmon resonance with a "hot spot" in surface-enhanced Raman scattering (SERS). However, for most molecules of interest the double resonance is not realized with the excitation frequencies normally used in Raman. The latter may limit the practical applications of SERS for trace analysis. Here, we report that Raman-inactive trinitrotoluene (TNT) lights up the ultrahigh Raman scattering of off-resonated p-aminobenzenethiol (PABT) through the formation of charge-transfer TNT-PABT complex on the top-closed flexible silver nanotube array. Raman hot spots can spontaneously form in a reversible way by the self-approaching of flexible nanotubes driven through the capillary force of solvent evaporation. Meanwhile, the PABT-TNT-PABT bridges between self-approaching silver nanotubes possibly form by the specific complexing and zwitterion interactions, and the resultant chromophores can absorb the visible light that matches with the incident laser and the localized surface plasmon of a silver nanotube array. The multiple spectral resonances lead to the huge enhancement of Raman signals of PABT molecules due to the presence of ultratrace TNT. The enhancement effect is repeatedly renewable by the reconstruction of molecular bridges and can selectively detect TNT with a limit of 1.5 × 10(-17) M. The results in this report provide the simple and supersensitive approach to the detection of TNT explosives and the possibility of building a robust Raman-based assay platform.

Core-shell nanostructured molecular imprinting fluorescent chemosensor for selective detection of atrazine herbicide.

To convert the binding events on molecularly imprinted polymers (MIPs) into physically detectable signals and to extract the templates completely are the great challenges in developing MIP-based sensors. In this paper, a core-shell nanostructure was employed in constructing the MIP chemosensor for the improvements of template extraction efficiency and imprinted sites accessibility. Vinyl-substituted zinc(II) protoporphyrin (ZnPP) was used as both fluorescent reporter and functional monomer to synthesize atrazine-imprinted polymer shell at silica nanoparticle cores. The template atrazine coordinates with the Lewis acid binding site Zn of ZnPP to form a complex for the molecular imprinting polymerization. These imprinted sites are located in polymer matrix of the thin shells (~8 nm), possessing better accessibility and lower mass-transfer resistance for the target molecules. The fluorescence properties of ZnPP around the imprinted sites will vary upon rebinding of atrazine to these imprinted sites, realizing the conversion of rebinding events into detectable signals by monitoring fluorescence spectra. This MIP probe showed a limit of detection (LOD) of about 1.8 µM for atrazine detection. The core-shell nanostructured MIP method not only improves the sensitivity, but also shows high selectivity for atrazine detection when compared with the non-molecular imprinted counterparts.

Surface-enhanced Raman scattering sensor for theophylline determination by molecular imprinting on silver nanoparticles.

A surface-enhanced Raman scattering (SERS)-based sensor for the determination of theophylline (THO) has been developed by imprinting the target molecules on the surface of silver nanoparticles. The desired recognition sites are generated after template removal and homogeneous distribution on the silver nanoparticles that have been incorporated within polymer matrix by the in situ reduction of theophylline-silver complexes, providing molecular recognition ability and SERS active surfaces. The theophylline molecules, complementary to the shape, size, and functionality of the recognition cavities, can selectively bind to the recognition sites at the surface of silver nanoparticles driven by the formation of hydrogen bonding and surface coordination. It has been demonstrated that the SERS signals of the theophylline molecules captured on the surface of the silver nanoparticles have a good reproducibility and a dose-response relationship to the target analytes, showing the potential for reliable identification and quantification of the bioactive compound. The molecular imprinting-based SERS sensor, like antibodies or enzymes, also possesses the ability to distinguish theophylline from the closely related structure caffeine due to the variations of molecular size and shape as well as the different affinity to silver ions.

Phosphorylation-Dependent SERS Readout for Activity Assay of Protein Kinase A in Cell Extracts.

Protein kinases are key regulators of cell function, the abnormal activity of which may induce several human diseases, including cancers. Therefore, it is of great significance to develop a sensitive and reliable method for assaying protein kinase activities in real biological samples. Here, we report the phosphorylation-dependent surface-enhanced Raman scattering (SERS) readout of spermine-functionalized silver nanoparticles (AgNPs) for protein kinase A (PKA) activity assay in cell extracts. In this assay, the presence of PKA would phosphorylate and alter the net charge states of Raman dye-labeled substrate peptides, and the resulting anionic products could absorb onto the AgNPs with cationic surface charge through electrostatic attraction. Meanwhile, the Raman signals of dyes labeled on peptides were strongly enhanced by the aggregated AgNPs with interparticle hot spots formed in assay buffer. The SERS readout was directly proportional to the PKA activity in a wide range of 0.0001-0.5 U·µL-1 with a detection limit as low as 0.00003 U·µL-1. Moreover, the proposed SERS-based assay for the PKA activity was successfully applied to monitoring the activity and inhibition of PKA in real biological samples, particularly in cell extracts, which would be beneficial for kinase-related disease diagnostics and inhibitor screening.