A novel nib-like design for microfabricated nanospray tips

AbstractWe present here novel tips for nanoelectrosray ionization-mass spectrometry (ESI-MS) applications. These ionization sources have a planar geometry in the shape of a nib. Their functioning is based on a principle much akin to that of a fountain pen in that fluids are actuated by capillarity. Once a voltage is applied, an electrospray is formed at the nib tip. The nib fabrication relies on micromachining techniques using the epoxy-based negative photoresist SU-8 and a double exposure photolithographic process. Two types of nib-like sources were fabricated; they were made either conductive by metallization with a nickel layer or non-conductive but hydrophilic by covering them with a SiO2 layer. In the latter case, the HV was applied via a Pt wire inserted into the reservoir feature of the nib. The nib-like sources were tested on an ion trap mass spectrometer using Gramicidin S samples at concentrations as low as 1 μM and ionization voltages as low as 1.2 kV. We have observed a good overall stability of the spray during the tests with no marked decrease in the signal intensity even under extreme conditions

Multiple signaling pathways regulate the transcriptional activity of the orphan nuclear receptor NURR1

The orphan nuclear receptor nurr1 (NR4A2) is an essential transcription factor for the acquisition and maintenance of the phenotype of dopamine (DA)-synthesizing neurons in the mesencephalon. Although structurally related to ligand-regulated nuclear receptors, nurr1 is functionally atypical due to its inability to bind a cognate ligand and to activate transcription following canonical nuclear receptor (NR) rules. Importantly, the physiological stimuli that activate this NR and the signaling proteins that regulate its transcriptional activity in mesencephalic neurons are unknown. We used an affinity chromatography approach and CSM14.1 cells of mesencephalic origin to isolate and identify several proteins that interact directly with nurr1 and regulate its transcriptional activity. Notably, we demonstrate that the mitogen-activated protein kinases, ERK2 and ERK5, elevate, whereas LIM Kinase 1 inhibits nurr1 transcriptional activity. Furthermore, nurr1 recruits ERK5 to a NBRE-containing promoter and is a potential substrate for this kinase. We have identified amino acids in the A/B domain of nurr1 important for mediating the ERK5 activating effects on nurr1 transcriptional activity. Our results suggest that nurr1 acts as a point of convergence for multiple signaling pathways that likely play a critical role in differentiation and phenotypic expression of dopaminergic (DAergic) neurons

Screening of pharmaceuticals and hormones at regional scale, in surface and groundwaters intended to human consumption

International audienceAs part of a regional screening to evaluate the risk, for the health of populations, to certain classes of emerging substances, several families of pharmaceuticals and hormones were looked for in waters intended to drinking. Thus, 52 substances were investigated in 71 surface waters and 70 groundwaters. Results indicate that no water was free of pollutants, regardless of its origin (surface or groundwater) and the season of collect. The pharmaceuticals most frequently detected and with the highest concentration levels were salicylic acid, carbamazepine and acetaminophen. Among hormones, testosterone, androstenedione and progesterone were detected in almost all the samples. Globally the groundwaters were less contaminated than surface waters in regards pharmaceuticals frequencies and levels. On the other side, androgens and progestagens were present with comparable frequencies and levels in both compartments. The risk linked to the presence of these substances on human health is discussed

Development of a Multi-Residue Analytical Method for Trace Analysis of Additives and Degradation Products from Plastic Packaging into Solutions by SPE-HPLC-MS/MS

International audienc

Développement d'une méthode d'analyse multi-résidus permettant l'étude de la bioaccumulation de polluants émergents dans des micro-organismes aquatiques d'eau douce par extraction miniaturisée de type QuEChERS suivie d'une analyse par NanoLC-MS/MS

communication par afficheNational audienc

Chemical, microbiological, spatial characteristics and impacts of contaminants from urban catchments: CABRRES project

International audienc

Statistical evaluation of the influence of soil properties on recoveries and matrix effects during the analysis of pharmaceutical compounds and steroids by quick, easy, cheap, effective, rugged and safe extraction followed by liquid chromatography-tandem mass spectrometry

International audienceNumerous chemical products are dispersed in our environment. Many of them are recognized as harmful to humans and the ecosystem. Among these harmful substances are antibiotics and steroid hormones. Currently, very few data are available on the presence and fate of these substances in the environment, in particular for solid matrices, mainly due to a lack of analytical methodologies. Indeed, soil is a very complex matrix, and the nature and composition of the soil has a significant impact on the extraction efficiency and the sensitivity of the method. For this reason a statistical approach was performed to study the influence of soil parameters (clay, silt, sand and organic carbon percentages and cation exchange capacity (CEC)) on recoveries and matrix effects of various pharmaceuticals and steroids. Thus, an analysis of covariance (ANCOVA) was performed when several substances were analyzed simultaneously, whereas a Pearson correlation was used to study the compounds individually. To the best of our knowledge, this study is the first time such an experiment was performed. The results showed that clay and organic carbon percentages as well as the CEC have an impact on the recoveries of most of the target substances, the variables being anti-correlated. This result suggests that the compounds are trapped in soils with high levels of clay and organic carbon and a high CEC. For the matrix effects, it was shown that the organic carbon content has a significant effect on steroid hormones and penicillin G matrix effects (positive correlation). Finally, interaction effects (first order) were evaluated. This latter point corresponds to the crossed effects that occur between explanatory variables (soil parameters). Indeed, the value taken by an explanatory variable can have an influence on the effect that another explanatory variable has on a dependent variable. For instance, it was shown that some parameters (silt, sand) have an impact on the effect that clay content has on recoveries. Besides, CEC and silt affect the influence that organic carbon percentage has on matrix effect. This original approach provides a better understanding of the complex interactions that occur in soil and could be useful to understand and predict the performance of an analytical method

Development of an analytical method for the targeted screening and multi-residue quantification of environmental contaminants in urine by liquid chromatography coupled to high resolution mass spectrometry for evaluation of human exposures

International audienceThe aim of this study was to develop an analytical method and contribute to the assessment of the Exposome. Thus, a targeted analysis of a wide range of contaminants in contact with humans on daily routines in urine was developed. The method focused on a list of 38 contaminants, including 12 pesticides, one metabolite of pesticide, seven veterinary drugs, five parabens, one UV filter, one plastic additive, two surfactants and nine substances found in different products present in the everyday human environment. These contaminants were analyzed by high performance liquid chromatography coupled to high resolution mass spectrometry (HPLC-HRMS) with a quadrupole-time-of-flight (QqToF) instrument from a raw urinary matrix. A validation according to the FDA guidelines was employed to evaluate the specificity, linear or quadratic curve fitting, inter- and intra-day precision, accuracy and limits of detection and quantification (LOQ). The developed analysis allows for the quantification of 23 contaminants in the urine samples, with the LOQs ranging between 43 ng.mL(-1) and 113.2 ng.mL(-1). This method was applied to 17 urine samples. Among the targeted contaminants, four compounds were detected in samples. One of the contaminants (tributyl phosphate) was detected below the LOQ, The three others (4-hydroxybenzoic acid, sodium dodecylbenzenesulfonate and O,O-diethyl thiophosphate potassium) were detected but did not fulfill the validation criteria for quantification. Among these four compounds, two of them were found in all samples: tributyl phosphate and the surfactant sodium dodecylbenzenesulfonat

Occurrence of pharmaceuticals and hormones in drinking water treated from surface waters

International audienceThe levels of a wide variety of pharmaceuticals and hormones, in source and potable-water supplies of French drinking water treatment plants, were assessed. In surface waters, 27 of the 51 target compounds were determined at least once. Paracetamol, salicylic acid and carbamazepine were quantified in more than 80% of samples. The highest concentration of 71 ng/L was observed for paracetamol. Twelve other substances were widely found in the surface waters studied, contaminating between 33 and 80% of the samples. These compounds include analgesics, psychotropic drugs, antibiotics and beta-blockers consistent with the French consumption, as well as natural hormones (oestrone, progesterone and androgens) and synthetic progestatives. In drinking water supplies, 25 compounds were also present, salicylic acid being the most frequently detected. Carbamazepine and the β-blocker atenolol found at lower levels (maximum 2 ng/L), are also present in more than 30% of the contaminated drinking waters. The pharmaceuticals exhibit different reactivity towards the treatments, while progestagens and androgens seem resistant to most of them. The effectiveness of the treatments is discussed, as well as the consequences of the presence of all these compounds on human health. This is the first time that such a long list of compounds (51) is proposed to assessment, and consequently this study provides the first data on pharmaceuticals and steroids occurrences in French drinking waters and represents a basis for the assessment of risks for humans. Moreover, at the international level, this is the first time that so many substances are quantified in drinking water, due to the very low detection limits, especially in the case of the hormones

Large screening of pharmaceuticals and hormones in sludge based on LC-ToF-MS

communication par afficheInternational audienceEcosystems are potentially contaminated by many chemical substances from domestic activities, through the spreading of treated sewage sludge. Indeed during the last thirty years, the application of municipal sludge from urban to agricultural soils is the option favoured internationally for sludge management as it contributes positively to recycling nutrients, soil properties and fertility. The literature data indicate that the removal efficiencies of organic contaminants in sewage treatment plants vary between 24 and 100% depending on the contaminants and treatment processes, which means that significant percentages of products can be present in the sludge. Steroid sex hormones and pharmaceuticals are considered emerging environmental contaminants of particular concern, as many of them display biologically active properties (including endocrine-disrupting). At the European level, few studies exist on the characterization of these emerging substances in sludge or on the assessment of health and environmental risks associated with their use. This is partly explained by the difficulties of detection and quantification of such pollutants in the solid phases. It is, indeed, a real analytic challenge given the diversity of analytes, their presence generally in trace amounts and the complexity of the matrix which makes difficult the extraction step. Thus it appears that the development of analytical methods sensitive, reliable and robust is an essential step for the characterization of emerging substances in sludge. In this context, the aim of the study was to develop a method for the large screening of pharmaceuticals and hormonal steroids in sludge. Therefore, nearly two hundred substances were analyzed by liquid chromatography-time-of-flight mass spectrometry. The analysis of complex matrices such as sludge needed a rigorous sample preparation to obtain a repeatable and enough sensitive analysis to achieve the detection limits required. For this purpose, an extraction step using the QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) method was set up. This analytical methodology was successfully applied to various kinds of sludge (limed, digested, dried, liquid, composted) collected in several sewage works in France