Background New psychoactive substances constitute a growing and dynamic class of abused drugs in the United States. On July 12, 2016, a synthetic cannabinoid caused mass intoxication of 33 persons in one New York City neighborhood, in an event described in the popular press as a “zombie” outbreak because of the appearance of the intoxicated persons. Methods We obtained and tested serum, whole blood, and urine samples from 8 patients among the 18 who were transported to local hospitals; we also tested a sample of the herbal “incense” product “AK-47 24 Karat Gold,” which was implicated in the outbreak. Samples were analyzed by means of liquid chromatography-quadrupole time-of-flight mass spectrometry. Results The synthetic cannabinoid methyl 2-(1-(4-fluorobenzyl)-1H-indazole-3-carboxamido)-3-methylbutanoate (AMB-FUBINACA, also known as MMB-FUBINACA or FUB-AMB) was identified in AK-47 24 Karat Gold at a mean (±SD) concentration of 16.0±3.9 mg per gram. The de-esterified acid metabolite was found in the serum or whole blood of all eight patients, with concentrations ranging from 77 to 636 ng per milliliter. Conclusions The potency of the synthetic cannabinoid identified in these analyses is consistent with strong depressant effects that account for the “zombielike” behavior reported in this mass intoxication. AMB-FUBINACA is an example of the emerging class of “ultrapotent” synthetic cannabinoids and poses a public health concern. Collaboration among clinical laboratory staff, health professionals, and law enforcement agencies facilitated the timely identification of the compound and allowed health authorities to take appropriate action.
Early detection of HIV infection is the best way to prevent spread of the disease and to improve the efficiency of the antiretroviral therapy. Nucleic acid amplification tests (NAAT) have become the gold-standard for detecting low-concentrations of the virus in blood. However, these methods are technically demanding and cost-prohibitive in developing countries. Immunoassays are more affordable and can be more easily adapted for point-of-care diagnosis. However, the sensitivity so far of these methods has been too low. We here report the development of a sandwich immunoassay that combines nanomechanical and optoplasmonic transduction methods for detecting the HIV-1 capsid antigen p24 in human serum. The immunoreactions take place on the surface of a compliant microcantilever where gold nanoparticles are used as both mechanical and plasmonic labels. The microcantilever acts as both a mechanical resonator and an optical cavity for the transduction of the mechanical and plasmonic signals. The limit of detection of the immunoassay is 10-17 g/mL that is equivalent to one virion in 10 mL of plasma. This is 5 orders of magnitude better than last generation of approved immunoassays and 2 orders of magnitude better than NAAT. This technology meets the demands to be produced en masse at low cost and the capability for miniaturization to be used at the point-of-care.
Crystallization of noble metal atoms usually leads to the highly symmetric face-centred cubic phase that represents the thermodynamically stable structure. Introducing defective microstructures into a metal crystal lattice may induce distortions to form non-face-centered cubic phases when the lateral dimensions of objects decrease down to nanometre scale. However, stable non-face-centered cubic phases have not been reported in noble metal nanoparticles. Here we report that a stable body-centred tetragonal phase is observed in silver nanoparticles with fivefold twinning even at ambient conditions. The body-centered tetragonal phase originates from the distortion of cubic silver lattices due to internal strains in the twinned nanoparticles. The lattice distortion in the centre of such a nanoparticle is larger than that in the surfaces, indicating that the nanoparticle is composed of a highly strained core encapsulated in a less-strained sheath that helps stabilize the strained core.
The staining of neurons with silver began in the 1800s, but until now the great resolving power of the laser scanning confocal microscope has not been utilized to capture the in-focus and three-dimensional cytoarchitecture of metal-impregnated cells. Here, we demonstrate how spectral confocal microscopy, typically reserved for fluorescent imaging, can be used to visualize metal-labeled tissues. This imaging does not involve the reflectance of metal particles, but rather the excitation of silver (or gold) nanoparticles and their putative surface plasmon resonance. To induce such resonance, silver or gold particles were excited with visible-wavelength laser lines (561 or 640 nm), and the maximal emission signal was collected at a shorter wavelength (i.e., higher energy state). Because the surface plasmon resonances of noble metal nanoparticles offer a superior optical signal and do not photobleach, our novel protocol holds enormous promise of a rebirth and further development of silver- and gold-based cell labeling protocols.
In this work, a simple method for alcohol synthesis with high enantiomeric purity was proposed. For this, colloidal gold and silver surface modifications with 3-mercaptopropanoic acid and cysteamine were used to generate carboxyl and amine functionalized gold and silver nanoparticles of 15 and 45 nm, respectively. Alcohol dehydrogenase from Thermoanaerobium brockii (TbADH) and its cofactor (NADPH) were physical and covalent (through direct adsorption and using cross-linker) immobilized on nanoparticles' surface. In contrast to the physical and covalent immobilizations that led to a loss of 90% of the initial enzyme activity and 98% immobilization, the use of a cross-linker in immobilization process promoted a loss to 30% of the initial enzyme activity and >92% immobilization. The yield of NADPH immobilization was about 80%. The best results in terms of activity were obtained with Ag-citr nanoparticle functionalized with carboxyl groups (Ag-COOH), Au-COOH(CTAB), and Au-citr functionalized with amine groups and stabilized with CTAB (Au-NH2(CTAB)) nanoparticles treated with 0.7% and 1.0% glutaraldehyde. Enzyme conformation upon immobilization was studied using fluorescence and circular dichroism spectroscopies. Shift in ellipticity at 222 nm with about 4 to 7 nm and significant decreasing in fluorescence emission for all bioconjugates were observed by binding of TbADH to silver/gold nanoparticles. Emission redshifting of 5 nm only for Ag-COOH-TbADH bioconjugate demonstrated change in the microenvironment of TbADH. Enzyme immobilization on glutaraldehyde-treated Au-NH2(CTAB) nanoparticles promotes an additional stabilization preserving about 50% of enzyme activity after 15 days storage. Nanoparticles attached-TbADH-NADPH systems were used for enantioselective (ee > 99%) synthesis of (S)-7-hydroxy-2-tetralol.
In the quest for producing an effective clinically relevant therapeutic agent, scalability, repeatability, and stability are paramount. In this paper, gold nanoparticles (GNPs) with precisely controlled near infrared (NIR) absorption are synthesized by a single step reaction of HAuCl4 and Na2S2O3, without assistance of additional templates, capping reagents or seeds. The anisotropy in the shape of gold nanoparticles offers high NIR absorption making it therapeutically relevant. The synthesized products consist of GNPs with different shape and size, including small spherical colloid gold particles and non-spherical gold crystals. The NIR absorption wavelengths and particle size increase with increasing molar ratio of HAuCl4/Na2S2O3. Non-spherical gold particles can be further purified and separated by centrifugation to improve the NIR absorbing fraction of particles. In-depth studies reveal that GNPs with good structural and optical stability only form in a certain range of the HAuCl4/Na2S2O3 molar ratio, whereas higher molar ratios result in unstable GNPs, which lose their NIR absorption peak due to decomposition and reassembly via Ostwald ripening. Tuning the optical absorption of the gold nanoparticles in the NIR regime via a robust and repeatable method will improve many applications requiring large quantities of desired NIR absorbing nanoparticles.
A simple method for the fabrication of porous silicon (Si) by metal-assisted etching was developed using gold nanoparticles as catalytic sites. The etching masks were prepared by spin-coating of colloidal gold nanoparticles onto Si. An appropriate functionalization of the gold nanoparticle surface prior to the deposition step enabled the formation of quasi-hexagonally ordered arrays by self-assembly which were translated into an array of pores by subsequent etching in HF solution containing H2O2. The quality of the pattern transfer depended on the chosen preparation conditions for the gold nanoparticle etching mask. The influence of the Si surface properties was investigated by using either hydrophilic or hydrophobic Si substrates resulting from piranha solution or HF treatment, respectively. The polymer-coated gold nanoparticles had to be thermally treated in order to provide a direct contact at the metal/Si interface which is required for the following metal-assisted etching. Plasma treatment as well as flame annealing was successfully applied. The best results were obtained for Si substrates which were flame annealed in order to remove the polymer matrix - independent of the substrate surface properties prior to spin-coating (hydrophilic or hydrophobic). The presented method opens up new resources for the fabrication of porous silicon by metal-assisted etching. Here, a vast variety of metal nanoparticles accessible by well-established wet-chemical synthesis can be employed for the fabrication of the etching masks.
This paper describes a microparticle delivery device that generates a plasma jet through laser ablation of a thin metal foil and uses the jet to accomplish particle delivery into soft living targets for transferring biological agents. Pure gold microparticles of 1 µm size were coated with a plasmid DNA, pIG121Hm, and were deposited as a thin layer on one surface of an aluminum foil. The laser (Nd:YAG, 1064 nm wavelength) ablation of the foil generated a plasma jet that carried the DNA coated particles into the living onion cells. The particles could effectively penetrate the target cells and disseminate the DNA, effecting the transfection of the cells. Generation of the plasma jet on laser ablation of the foil and its role as a carrier of microparticles was visualized using a high-speed video camera, Shimadzu HPV-1, at a frame rate of 500 kfps (2 µs interframe interval) in a shadowgraph optical set-up. The particle speed could be measured from the visualized images, which was about 770 m/s initially, increased to a magnitude of 1320 m/s, and after a quasi-steady state over a distance of 10 mm with an average magnitude of 1100 m/s, started declining, which typically is the trend of a high-speed, pulsed, compressible jet. Aluminum launch pad (for the particles) was used in the present study to make the procedure cost-effective, whereas the guided, biocompatible launch pads made of gold, silver or titanium can be used in the device during the actual clinical operations. The particle delivery device has a potential to have a miniature form and can be an effective, hand-held drug/DNA delivery device for biological applications.
We report on how to quantify the binding affinity between a nanoparticle and chemical functional group using various experimental methods such as cantilever assay, PeakForce quantitative nanomechanical property mapping, and lateral force microscopy. For the immobilization of Au nanoparticles (AuNPs) onto a microscale silicon substrate, we have considered two different chemical functional molecules of amine and catecholamine (dopamine was used here). It is revealed that catecholamine-modified surface is more effective for the functionalization of AuNPs onto the surface, which is compared with the amine-modified surface from our various experiments. The dimensionless parameter (i.e., ratio of binding affinity) introduced in this work from such experiments is useful in quantitatively depicting such binding affinity, indicating that the binding affinity and stability between AuNPs and catecholamine is approximately 1.5 times stronger than that of amine. Our study sheds light on the experiment-based quantitative characterization of the binding affinity between nanomaterial and chemical groups, which will eventually provide an insight into how to effectively design the functional material using chemical groups.
Carbon nanotubes (CNTs) are often used as conductive fillers in composite materials, but electrical conductivity is limited by the maximum filler concentration that is necessary to maintain composite structures. This paper presents further improvement in electrical conductivity by precipitating gold nanoparticles onto CNTs. In our composites, the concentrations of CNTs and poly (vinyl acetate) were respectively 60 and 10 vol%. Four different gold concentrations, 0, 10, 15, or 20 vol% were used to compare the influence of the gold precipitation on electrical conductivity and thermopower of the composites. The remaining portion was occupied by poly(3,4-ethylenedioxythiophene) poly(styrenesulfonate), which de-bundled and stabilized CNTs in water during synthesis processes. The concentrations of gold nanoparticles are below the percolation threshold of similar composites. However, with 15-vol% gold, the electrical conductivity of our composites was as high as ∼6×10(5) S/m, which is at least ∼500% higher than those of similar composites as well as orders of magnitude higher than those of other polymer composites containing CNTs and gold particles. According to our analysis with a variable range hopping model, the high conductivity can be attributed to gold doping on CNT networks. Additionally, the electrical properties of composites made of different types of CNTs were also compared.