C60 ion sputtering of layered organic materials

Two different organic materials, Irganox1010 and Irganox3114, were vacuum deposited as alternating layers. The layers of Irganox3114 were thin (∼2.5 nm) in comparison to the Irganox1010 (∼55 or ∼90 nm); we call these ‘organic delta layers’. Both materials are shown to have identical sputtering yields and the alternating layers may be used to determine some of the important metrological parameters for cluster ion beam depth profiling of organic materials. The sputtering yield for C₆₀ ions is shown to diminish with ion dose. Comparison with atomic force microscopy data from films of pure Irganox1010, demonstrates that the depth resolution is limited by the development of topography. Secondary ion intensities are a well-behaved function of sputtering yield and may be employed to obtain useful analytical information. Organic delta layers are shown to be valuable reference materials for comparing the capabilities of different cluster ion sources and experimental arrangements for the depth profiling of organic materials.     

Electrical characterization of high-k gate dielectrics on semiconductors

This paper reviews the following electrical characterization techniques for measuring the microscopic bonding structures, impurities, and electrically active defects in advanced CMOS gate stacks: (1) inelastic electron tunneling spectroscopy (IETS), (2) lateral profiling of threshold voltages, interface-trap density, and oxide charge density distributions along the channel of a MOSFET, and (3) pulse agitated substrate hot electron injection (PASHEI) technique for measuring trapping effects in the gate dielectric at low and modest gate voltages.     

Refining search terms for nanotechnology

The ability to delineate the boundaries of an emerging technology is central to obtaining an understanding of the technology’s research paths and commercialization prospects. Nowhere is this more relevant than in the case of nanotechnology (hereafter identified as “nano”) given its current rapid growth and multidisciplinary nature. (Under the rubric of nanotechnology, we also include nanoscience and nanoengineering.) Past efforts have utilized several strategies, including simple term search for the prefix nano, complex lexical and citation-based approaches, and bootstrapping techniques. This research introduces a modularized Boolean approach to defining nanotechnology which has been applied to several research and patenting databases. We explain our approach to downloading and cleaning data, and report initial results. Comparisons of this approach with other nanotechnology search formulations are presented. Implications for search strategy development and profiling of the nanotechnology field are discussed.

Iodine-mediated one-pot synthesis of C-3 acylated indolizines from pyridines,aryl methyl ketones and acrylate derivatives

An I₂/CuI-promoted multi-component reaction from pyridines, aryl methyl ketones and electron deficient acrylates has been accomplished in a “one-pot” manner, which provides a straightforward and efficient access to C-3 acylated indolizines. The key intermediate of N-ylides is hypothesized to be generated in situ from pyridines and (hetero)aryl methyl ketones in the presence of iodine. This method has been applied in the synthesis of two molecules with anticonvulsant and anti-inflammatory activities.     

Volatile compounds profiling by using proton transfer reaction‐time of flight‐mass spectrometry (PTR‐ToF‐MS). The case study of dark chocolates organoleptic differences

Direct‐injection mass spectrometry (DIMS) techniques have evolved into powerful methods to analyse volatile organic compounds (VOCs) without the need of chromatographic separation. Combined to chemometrics, they have been used in many domains to solve sample categorization issues based on volatilome determination. In this paper, different DIMS methods that have largely outperformed conventional electronic noses (e‐noses) in classification tasks are briefly reviewed, with an emphasis on food‐related applications. A particular attention is paid to proton transfer reaction mass spectrometry (PTR‐MS), and many results obtained using the powerful PTR‐time of flight‐MS (PTR‐ToF‐MS) instrument are reviewed. Data analysis and feature selection issues are also summarized and discussed. As a case study, a challenging problem of classification of dark chocolates that has been previously assessed by sensory evaluation in four distinct categories is presented. The VOC profiles of a set of 206 chocolate samples classified in the four sensory categories were analysed by PTR‐ToF‐MS. A supervised multivariate data analysis based on partial least squares regression‐discriminant analysis allowed the construction of a classification model that showed excellent prediction capability: 97% of a test set of 62 samples were correctly predicted in the sensory categories. Tentative identification of ions aided characterisation of chocolate classes. Variable selection using dedicated methods pinpointed some volatile compounds important for the discrimination of the chocolates. Among them, the CovSel method was used for the first time on PTR‐MS data resulting in a selection of 10 features that allowed a good prediction to be achieved. Finally, challenges and future needs in the field are discussed.     

Serum Proteomic Analysis of Cannabis Use Disorder in Male Patients

Cannabis use has been growing recently and it is legally consumed in many countries. Cannabis has a variety of phytochemicals including cannabinoids, which might impair the peripheral systems responses affecting inflammatory and immunological pathways. However, the exact signaling pathways that induce these effects need further understanding. The objective of this study is to investigate the serum proteomic profiling in patients diagnosed with cannabis use disorder (CUD) as compared with healthy control subjects. The novelty of our study is to highlight the differentially changes proteins in the serum of CUD patients. Certain proteins can be targeted in the future to attenuate the toxicological effects of cannabis. Blood samples were collected from 20 male individuals: 10 healthy controls and 10 CUD patients. An untargeted proteomic technique employing two-dimensional difference in gel electrophoresis coupled with mass spectrometry was employed in this study to assess the differentially expressed proteins. The proteomic analysis identified a total of 121 proteins that showed significant changes in protein expression between CUD patients (experimental group) and healthy individuals (control group). For instance, the serum expression of inactive tyrosine protein kinase PEAK1 and tumor necrosis factor alpha-induced protein 3 were increased in CUD group. In contrast, the serum expression of transthyretin and serotransferrin were reduced in CUD group. Among these proteins, 55 proteins were significantly upregulated and 66 proteins significantly downregulated in CUD patients as compared with healthy control group. Ingenuity pathway analysis (IPA) found that these differentially expressed proteins are linked to p38MAPK, interleukin 12 complex, nuclear factor-κB, and other signaling pathways. Our work indicates that the differentially expressed serum proteins between CUD and control groups are correlated to liver X receptor/retinoid X receptor (RXR), farnesoid X receptor/RXR activation, and acute phase response signaling.     

Characterization of erythropoietin biosimilars using mass spectrometric CID and HCD techniques

Recombinant human erythropoietin (rHuEPO) is the first cloned hematopoietic growth factor available for pharmaceutical treatment, especially anemia, since 1988. Unfortunately, the ability of rHuEPO in boosting erythropoiesis, and thus aerobic capacity has led to its abuse in endurance sport. Besides, the expiry of the original rHuEPO patent has resulted in many biosimilars being produced which led to special requirements regarding quality control. As a consequence, there is a huge demand for all rHuEPOs to be well characterized for the ease of identification, differentiation, and detection. Glycoproteomic mass spectrometry, the most current promising approach for rHuEPOs analysis, was employed to characterize 4 rHuEPOs including epoetin-α, epoetin-β, darbepoetin-α and Mircera. Via nanoLC-ESI-MS/MS, distinct glycoproteomic profiles of each rHuEPO have been achieved for differential analysis. With two different fragmentation methods, collision-induced dissociation (CID) and higher-energy collision dissociation (HCD), maximum of 75%, 70%, 70%, and 77% protein sequence coverages were attained for epoetin-α, epoetin-β, darbepoetin-α and Mircera, respectively. From the peptides/glycopeptides mixture, similar and unique peptides/glycopeptides (biomarkers) for each rHuEPO have been identified. With the discovery of high quality and unique biomarkers, a more standardized and efficient method for quality control and rHuEPO abuse detection can be developed.     

Position-specific 15N isotope analysis in organic molecules: A high-precision 15N NMR method to determine the intramolecular 15N isotope composition and fractionation at natural abundance

The position-specific ¹⁵N isotope content in organic molecules, at natural abundance, is for the first time determined by using a quantitative methodology based on ¹⁵N Nuclear Magnetic Resonance (NMR) spectrometry. ¹⁵N NMR spectra are obtained by using an adiabatic “Full-Spectrum” INEPT sequence in order to make possible ¹⁵N NMR experiments with a high signal-to-noise ratio (>500), to reach a precision with a standard deviation below 1‰ (0.1%). This level of precision is required for observing small changes in ¹⁵N content associated to ¹⁵N isotope effects. As an illustration, the measurement of an isotopic enrichment factor ε for each ¹⁵N isotopomer is presented for 1-methylimidazole induced during a separation process on a silica column. The precision expressed as the long-term repeatability of the methodology is good enough to evaluate small changes in the ¹⁵N isotope contents for a given isotopomer. As observed for ¹³C, inverse and normal ¹⁵N isotope effects occur concomitantly, giving access to new information on the origin of the ¹⁵N isotope effects, not detectable by other techniques such as isotope ratio measured by Mass Spectrometry for which bulk (average) values are obtained.     

Identification of interactions between multiple components in Socheongryong‐tang using a plant profiling approach

Traditional herbal medicine consists of multiple components. There are interactions among the components, which affect both potency and toxicity. The preparation of herbal medicines can be a cause of interactions between multicomponents in herbs. To demonstrate the differences in multiherb interactions based on the preparation methods, the changes in the active components in the different preparations of Socheongryong‐tang (SCRT) were evaluated using metabolomics profiling. We performed multicomponent profiling of the decoction of SCRT (SCRTD) and individual herb mixture (SCRTM) using ultra‐high‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry (UPLC–QTOF–MS). Active compounds from SCRTD and SCRTM were identified using multivariate analysis, and the activities between the two groups were compared. We also evaluated the anti‐inflammatory effect of SCRT through investigating the protein expression of iNOS and COX‐2 in lipopolysaccharide‐induced macrophage RAW 264.7 cells in both groups. From the multivariate analysis, 53 active compounds that have different intensities between SCRTD and SCRTM were identified. The intensities of those components, such as ephedrines, glycyrrhizic acid, 6‐gingerol and (2E,4E,8Z,10E)‐N‐isobutyl‐2,4,8,10‐dodecatetraenamide, which is newly identified in Asiasarum heterotropoides, were mostly higher in SCRTD than in SCRTM, which was related to the anti‐inflammatory effect. From the iNOS inhibition test, it was found that SCRTD had a stronger anti‐inflammatory effect than SCRTM. It was demonstrated that multicomponent interactions can be changed by the preparation method, and finally the anti‐inflammatory effect in SCRT can be affected.     

Inkjet printing of gold nanoparticles onto a biologically relevant matrix to create quantitative test materials for time-of-flight secondary ion mass spectrometry

This study describes the use of inkjet printing for the preparation of test materials containing gold nanoparticles (AuNPs) on a biologically relevant matrix and discusses the methods of using time-of-flight secondary ion mass spectrometry (ToF-SIMS) for their spatially resolved quantification. Evaluation of test materials containing AuNPs with nominal diameters of (30, 80, 100, and 150) nm deposited onto gelatin with loadings ranging from 34 fg up to 67 000 fg per spot suggests that ToF-SIMS has the sensitivity and the dynamic range to quantify NP deposits in a biological matrix at toxicologically relevant concentrations, although it was not capable of reliably determining the size of the AuNPs from the intensity data. Regardless, the ability to extract intensity data from individual regions of interest (ROIs) showed that spatially resolved quantification is possible, even when multiple features exist in a single image and in a single depth profile. The argon gas cluster source used for sputtering led to a matrix removal effect where the matrix surrounding the AuNPs became negligible, which may facilitate the preparation of quantitative test materials.