Thèse

Stage Master : La LC-TASTE : de la molécule à la saveur

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PhD thesis position: Development of a new technology of concurrent 2-dimension separation for characterization of nanoparticles towards nanomedicine applications

The PhD position is granted by the Agence Nationale de la Recherche (ANR) for 36 months starting from the 1st…

The PhD position is granted by the Agence Nationale de la Recherche (ANR) for 36 months starting from the 1st of January 2024. Project Description: This project aims at developing a novel concept and prototyping in separation science, called microscale 2D magneto-electrography (2D-ME). This concept will allow two simultaneous orthogonal migration dimensions in the same microchannel: capillary electrophoresis (CE) under a high electric field and magnetophoresis under a powerful magnetic field gradient. This new concept is expected to be better adapted for size, charge and shape characterization of nano objects (e.g., functionalized nanoparticles). Nanoparticles (NPs), including magnetic nanoparticles (MNPs) play important roles in diagnosis, drug delivery systems and nanomedicine.   Particularly for MNPs, size is also a key parameter when using them as contrast agents in magnetic resonance imaging or tumor radio-sensitization, for magnetic hyperthermia dedicated to thermosensitive drug delivery or cancer treatment [1]. For each family of MNPs, there is often a co-existence of various subpopulations and interferences (especially in biological fluids) with overlapping physical properties, rendering challenging their fine separation and characterization. This requires qualified methods to well separate their subpopulations and characterize them, in order to improve their synthesis to obtain the desired MNPs quality, which is mandatory for biomedical applications and drug delivery systems. Recently, particular attention has been paid to anisotropic MNPs with elongated shapes such as nanorods or nanochains as they exhibit improved magnetic properties for magnetic resonance imaging and magnetic hyperthermia in comparison to their spherical counterparts [2]. Such anisotropic MNPs are also featured by a higher blood circulation time and a prolonged retention in tumor sites compared to spherical NPs, as well as improved interaction with cells thanks to their cylindrical shape. It is however very challenging to separate and characterize anisotropic NPs using conventional separation approaches. From this urgent need, the first 2D-ME prototype to be developed in microfluidic format will be used for resolute charge, size and shape characterization of spheric MNPs and nanorods serving as innovative drug carriers. 2D-ME will also explore and control the nanometric heterogeneity as well as their interactions with biomolecules (e.g., blood proteins) to improve NPs synthesis and the quality of nanomedicine. This interdisciplinary project covers microfluidics, instrumentation, (bio)analytical chemistry, and nanoscience. This project will be supported by the complementary expertise of partners from Institut Néel (for magnetic field design modeling and micro-magnet parterning) and the Inorganic Colloids team of laboratory Physico-chimie des Electrolytes et Nanosystèmes InterfaciauX (PHENIX, Sorbonne university, for synthesis and characterization of magnetic nanoparticles). The PhD student will develop the 2D-ME system and protocols for pre-concentration, separation and characterization of tailored spheric MNPs synthesized by PHENIX. The 2D-ME system in microfluidic format will be developed, with the strong support of our group in purpose-made microfluidic and electrokinetic instrumentation [3, 4]. The PhD student, in close collaboration with Institut Néel, will try to propose different ways to combine the magnetic and electric fields in a microchannel to carry out 2D-ME of standard MNPs. The PhD student will then demonstrate the applicability of the developed system and methodology for separation of magnetic nanorods provided by PHENIX and monitoring their interaction with human plasma proteins to evaluate their behavior under biological conditions.   QUALIFICATION

• You are highly motivated to work at the boundary between microfluidics, instrumentation, bioanalytical chemistry and nanoscience.
• You have a master’s degree or equivalent (obtained within 4 years) in either Instrumentation or Analytical Chemistry / Nanoscience / Microfluidics
• You have practical experience in microfluidics and/or instrumentation and/or microfabrication, with a good sense of analytical chemistry
• Good knowledge about biochemistry and nanoparticles is advantageous.
• You have strong communication and presentation skills in English (verbal and written)
• You enjoy working independently and challenging scientific obstacles with an optimist aptitude.

  Send your application by e-mail before the 1^st of October 2023 to thanh-duc.mai@universite-paris-saclay.fr and claire.smadja@universite-paris-saclay.fr including your CV, motivation letter and recommendation letters from your previous supervisors / professors.   Refs: [1]       N.V.T. Nguyen, C. Smadja, M. Taverna, J.M. Siaugue, E. Secret, S. Elmousli, H.L.T. Nguyen, T.D. Mai, Electroosmotic flow modulation for improved electrokinetic preconcentration :  application to  capillary electrophoresis of fluorescent magnetic nanoparticles, Anal. Chim. Acta, 1161 (2021) 338466. [2]        S.E. Mousli-Saada, Elaboration de nanoparticules magnétiques anisotropes et étude de leurs voies d'internalisation cellulaire (PhD thesis), PHENIX - PHysicochimie des Electrolytes et Nanosystèmes InterfaciauX, https://theses.hal.science/tel-03884548 (2022) [3]       N.V.T. Nguyen, C. Smadja, M. Taverna, H.L.T. Nguyen, S. Descroix, T.D. Mai, On-line dual-stage enrichment via magneto-extraction and electrokinetic preconcentration: a new concept and instrumentation for capillary electrophoresis, Anal. Chim. Acta, 1255 (2023) 341141. [4]       T. Liénard--Mayor, J.S. Furter, M. Taverna, H.V. Pham, P.C. Hauser, T.D. Mai, Modular instrumentation for capillary electrophoresis with laser induced fluorescence detection using plug-and-play microfluidic, electrophoretic and optic modules, Anal. Chim. Acta, 1135 (2020) 47-54.

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Post-doc Offer (18 months): New Antibody’s format: strategies to evaluate their aggregation propensity for better developability

This postdoc is part of the large project ACCREDIA bringing together a network of industrial and academic partners funded by…

This postdoc is part of the large project ACCREDIA bringing together a network of industrial and academic partners funded by the French government aiming at improving the knowledge, skill, and methodologies in antibody developability. The project’s ambition is to create new antibody formats adapted to different routes of administration, in particular, the inhalation one, combining high-throughput antibody screening and engineering, in vitro and in vivo biological activity assessments. To achieve this goal, the immunogenicity of these new format antibodies, mainly due to immunogenic sequences or the formation of aggregates will be also investigated. The aim of the recruited post-doc is ; (i) to develop analytical strategies to characterize and understand the aggregation process and predict antibody sequence features that make an antibody a good candidate in terms of immunogenicity and (ii) to provide bioanalytical tools to monitor degradation/aggregation propensity of these new format antibodies according to the delivery route (lung, nasal…) and their formulation. New mAbs of different formats (Multispecific, ADC, …) will be produced by our partners using inovative engineering processes. Their degradation/aggregation pathways (under different stresses) will be thoroughly investigated (sub-unit involved,….). The impact of the formulations allowing the different routes of administration will also be evaluated. Different orthogonal analytical methods (preparative techniques e.g. FPLC, separation ones like HPLC, SEC, capillary electrophoresis eventually coupled to MS and, Taylor Dispersion Analysis) and spectroscopic ones (e.g. Circular dichroism, DLS, NTA…) will be developed for these purposes. The impact of the degraded forms on innate immunity cells will also be investigated in-vitro in close collaboration with the consortium partners. Laboratory: Institut Galien Paris Saclay (IGPS), UMR CNRS 8612, PNAS team; Henry Moissan building, 17 avenue des sciences, 91400 Orsay (https://www.umr-cnrs8612.universite-paris-saclay.fr/ ) IGPS is an interdisciplinary research institute and is considered as one of the main actors in Europe in the field of nanomedicine and gathers analytical and physico-chemists as well as biologists and pharmacologists. PNAS team has a strong background in protein and peptide analysis. IGPS benefits from the strong presence of national research organizations, numerous state-of-the-art facilities, and scientific platforms of the Paris-Saclay University. Starting date: October/November 2023, 18 months (extension might be possible) Financial support: PEPR contract 2023-2026 (ACCREDIA) Candidate profile: PhD, Analytical chemist interested by cell biology and Immunology. knowledge on mAbs/proteins analysis. To apply: send CV, cover letter and one or two references to claire.smadja@universite-paris-saclay.fr and myriam.taverna@universite-paris-saclay.fr Salary (gross) : ranging from 2889,51 to 4082,90 € per month depending on experience

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Offre de Thèse : Innovative sampling and suspect/non-targeted screening methods for exploring human perinatal exposure to chemicals of emerging concern

Background Conventional sampling and targeted quantitative methods dedicated to chemical analyses are available to support environmental, food and human monitoring,…

Background Conventional sampling and targeted quantitative methods dedicated to chemical analyses are available to support environmental, food and human monitoring, risk assessment, and risk management decisions. However, these approaches sometimes still suffer from a lack of sensitivity to characterize lowest exposed populations, a lack of feasibility for large population studies, and importantly only capture a limited number of a priori known and selected markers of exposure. Capturing the complex real human chemical exposome requires new conceptual frameworks and innovative methodological approaches, built on the latest generation of cutting-edge instrumentation that open the door to more rapid, high throughput, and holistic marker’s detection and identification. Combining innovative sampling (dry bloodspot, silicone wristbands) and/or biological matrices (cord blood, placenta, meconium…) with suspect and non-targeted screening approaches based on high resolution mass spectrometry (HRMS) today appear as promising methodological alternatives to widen our knowledge of the human chemical exposome. As formulated by several agencies (e.g. EFSA), early stage human exposure appears in particular as a high concern not yet well addressed, both in terms of risk assessment and link to health impact at latest stages (DoHAD concept). The aim of this project is to develop and conduct a proof-of-concept permitting to assess the performances, and illustrate the usefulness, of those innovative methods, as complementary to conventional and targeted approaches, with a focus on human samples collected from mother-newborn/child individuals. Objectives In this context, a research project is open for a Ph.D. candidate. This project aims to develop innovative analytical strategies focusing on perinatal exposure profiling via multidimensional and high-resolution mass spectrometry coupled with different types of chromatographic separations (LC-Q-Exactive/LC-Q-TOF/GC-Q-Exactive). The Ph.D. student's research work will thus consist of sample preparation, data generation, data analysis, and treatment to gain access to the characterization of the chemical exposure of individuals (Exposomics). Moreover, an additional part will be dedicated to evaluating the new sampling methods and comparing them to more invasive conventional techniques. This Ph.D. project is a part of a large European consortium on chemical exposure (PARC project “Partnership for Assessment of Risk of Chemicals”, EU Horizon EU Cofund, 2022-2029, https://www.eu-parc.eu/) – assembling more than 200 institutions from 28 countries. This consortium will offer the candidate a large networking and international experience. Supervisors Dr. Jean-Philippe ANTIGNAC Dr. Tarek MOUFAWAD Qualifications We are looking for a highly motivated scientist with a master degree in characterization of human exposure to chemicals. In detail, the candidate is expected to possess:  Strong chemical background with a M.Sc. in Chemistry, Chemical Engineering, Analytical Chemistry or equivalent  Hands on experience with analytical method development and advanced data analysis within chromatography and mass spectrometry (multidimensional and/or high resolution MS) workflows  Experience or knowledge about one or more of the following areas will be an advantage: o Chemical contaminants o Exposomics o Multivariate data analysis  Good laboratory skills  Good collaboration and communication skills (written and spoken English)  Structured and analytical working approach Salary The period of employment is 3 year, gross salary of 2044.12 €/month. Application Please submit your application before 30 July 2023. Applications must be submitted to jean-philippe.antignac@oniris-nantes.fr and tarek.moufawad@oniris-nantes.fr as one pdf file containing all materials to be given consideration. The file must include:  A covering letter  A curriculum vitae  Supporting letters

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Analytical Chemist – Engineer position

Background The HBM platform of LABERCA (ISO 9001 certified), has all facilities and cutting-edge mass spectrometry instrumentation (MS/MS and HRMS…

Background The HBM platform of LABERCA (ISO 9001 certified), has all facilities and cutting-edge mass spectrometry instrumentation (MS/MS and HRMS coupled to GC, LC and SFC) to assess human exposure to complex mixtures or organic chemicals. The end of 2023 will be devoted to the scaling-up of this biomonitoring activity, with the consolidation of a team of 4 people, consisting of a researcher in charge of the platform, a technician and two engineers, one of whom is the matter of the present recruitment. Tasks In relation with the platform manager and the technical support and innovation team of the laboratory, you will be in charge of setting up miniaturized and automated solutions for the preparation of human biological samples (urine and serum) in the scope of measuring markers of internal chemical exposure, in particular as a first stage organochlorine pesticides and PFAS. You will be responsible for the development, validation and training of the team, in the final objective of ISO 17025 accreditation of the developed methods.   Supervisors Dr. Emmanuelle BICHON, Head of the development and innovation Unit Ms Alicia GRIVAUD, Technical responsible of the HBM platform Qualifications We are looking for a highly motivated scientist with a Master or PhD degree and advanced experience in analytical chemistry applied to the analysis of chemical contaminants in biological matrices.

• Strong chemical background with a PhD in Chemistry, Analytical Chemistry or equivalent
• Strong hands on experience with:

• Sample preparation (extraction, purification and fractionation techniques)
• Chromatography coupled to mass spectrometry

• Data analysis
• Knowledge on accreditation body and quality management systems
• Good collaboration and communication skills (written and oral English)

  Salary The period of employment is 2 years (from oct 23), 2 200 euros net/month.   Application Please submit your application no later than 15^th July 2023. Applications must be submitted to emmanuelle.bichon@oniris-nantes.fr as one pdf file containing all materials to be given consideration. The file must include:

• A letter motivating the application (cover letter)
• A curriculum vitae

1 or 2 letters of support

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