Proteins and Nanotechnology in Analytical Sciecnes (PNAS)

The research topics of the team are dedicated to the development of new and original miniaturized analytical techniques. The aim is to develop micro and nano scale methods for the pre-concentration, separation, characterization and quantification of biomolecules such as peptides, proteins, and monoclonal antibodies. These methods are also developed to study the interaction between the molecules of interest and other species in biological media (drugs, DNA, biological barriers, delivery systems). The different developed techniques are used for (i) molecular diagnosis of pathologies or therapeutic follow-up via biomarkers analyses (ii) quality control and characterization of therapeutic proteins and biopharmaceuticals (iii) characterization of nano-objects notably the extracellular vesicles, antibody aggregates and nanoparticles (iv) the search for and validation of new disease biomarkers.

The lab is currently working on 6 main research topics:

• Development of innovative approaches for isolation and characterization of extracellular vesicles, as well as detection of exosomal biomarkers.
• Development of analytical methods to characterize and detect denaturated mAbs and small aggregates.
• Development of electrokinetic and nano-HPLC methods to improve the separation and detection o f proteins/peptides (preconcentration, detection by fluorescence or mass spectrometry).
• Synthesis of new stationary phases, solid supports or monoliths for biological samples treatment: enrichment, capture, enzymatic digestion.
• Conception of lab-in-droplets and development of novel instrumental concepts (Lego-CE, magneto-CE, multi-modal detection) integrating all the analysis steps for the miniaturization of diagnostic tools.
• Development of diagnostic tools and in vitro screening methods to test drug candidates against neurodegenerative diseases, type 2 diabetes, or glycosylation disorders.

• Isolation and Characterisation of extracellular vesicles
• Analyses of proteins, glycoproteins, phosphoproteins and their molecular interactions
• Electrokinetic separations (capillary electrophoresis, microfluic-CE, electrochromatography)
• Coupling of capillary electrophoresis and nano-LC to mass spectrometry
• Liquid chromatography separations (HPLC, nano-HPLC)
• Pre-concentration strategies: electrokinetic, on monolithic support and immunocapture
• Protein immobilization onto magnetic particles and functionalized surfaces
• Fluorescent tagging of peptides and proteins
• Development of miniaturized analytical instruments and methods for quality control of therapeutic proteins and/or molecular diagnosis of diseases
• Development of microsystems, Lab on chip, Point of Care and biosensors for health applications

MORANI Marco - PhD student
CROSNIER DE LASSICHERE Cédric
ROUBY Grégory
LE Minh-Thang
ROSSI Emilie
LABORIE Etienne
URAL Merve Seray
BATAILLE Jeanne
ABOUD Nacéra
ARAYA-FARIAS Monica
BERARDET Corentin
BRINET Dimitri
DZIOMBA Szymon
JACCOULET Emmanuel
RUEL Coralie

• 2MIB : Molecules, Materials, Instrumentation and Biosystems
• ITFA : Innovation Thérapeutique : du Fondamental à l’Appliqué
• Master 2 Biotechnologies Pharmaceutiques et Thérapies Innovantes :
  • Link Paris-Saclay
  • LinkUniversité Paris-Sud
  • @M2BPTI

Major publications

• Morani M, Mai TD, Krupova Z, Defrenaix P, Multi E, Riekkola M-L, Taverna M. Electrokinetic characterization of extracellular vesicles with capillary electrophoresis: A new tool for their identification and quantification. Anal Chim Acta. 2020 ; DOI : 10.1016/j.aca.2020.06.073
• N.V.T. Nguyen, C. Smadja, M. Taverna, S.E. Mouslic, E. Secret, J-M. Siaugue, L. T. H. Nguyen, T. D. Mai. Electroosmotic flow modulation for improved electrokinetic preconcentration: Application to capillary electrophoresis of fluorescent magnetic nanoparticles; Anal Chim Acta. 2021. DOI: 10.1016/j.aca.2021.338466

• Liénard--Mayor T, Furter J, Taverna M, Pham HV, Hauser P, Mai TD. Modular instrumentation for capillary electrophoresis with laser induced fluorescence detection using plug-and-play microfluidic, electrophoretic and optic modules. Anal Chim Acta. 2020 ; DOI : 10.1016/j.aca.2020.08.025

• Shao H, Reider B , Jarvas G, Guttman A, Jiang Z, Tran NT, Taverna M. On-line enrichment of N-glycans by immobilized metal-affinity monolith for capillary electrophoresis analysis. Anal Chim Acta. 2020 ; DOI : 10.1016/j.aca.2020.08.002

• Rouby G, Tran NT, Leblanc Y, Taverna M, Bihoreau N. Investigation of monoclonal antibody dimers in afinal formulated drug by separation techniquescoupled to native mass spectrometry. MABS. 2020 ; DOI : 10.1080/19420862.2020.1781743

• Nguyen NVT, Taverna M, Smadja C, Mai TD. Recent electrokinetic and microfluidic strategies for detection of amyloid beta peptide biomarkers: towards molecular diagnosis of Alzheimer's disease. Chemicals Records. 2020 ; DOI : 10.1002/tcr.202000103

• Rossi E, Tran N.T, Hirtz C, Lehmann S, Taverna M. Efficient extraction of intact HSA-Aß peptide complexes from sera: Toward albuminome biomarker identification. Talanta. 2020 ; DOI : 10.1016/j.talanta.2020.121002

• Le-Minh V,Halgand F, Van der Rest G, Taverna M, Smadja C. Conformation assessment of therapeutic monoclonal antibodies by SEC-MS: unravelling analytical biases for application to quality control. Journal of Pharmaceutical and Biomedical Analysis. 2020 ; DOI : 10.1016/j.jpba.2020.113252

• Crosnier de Lassichère C, Mai TD, Taverna M. Antibody-free detection of amyloid beta peptides biomarkers in cerebrospinal fluid using capillary isotachophoresis coupled with mass spectrometry. Journal of Chromatography A. 2019 ; DOI : 10.1016/j.chroma.2019.05.006

• Mai TD, Hauser PC, Descroix S, Crosnier de Lassichère C, Taverna M, Smadja C. In-capillary immuno-preconcentration with circulating bio-functionalized magnetic beads for capillary electrophoresis. Analytica Chimica Acta. 2019 ; DOI : 10.1016/j.aca.2019.02.006

• Le-Minh V, Tran NT, Makky A, Rosilio V, Taverna M, Smadja C. Capillary zone electrophoresis-native mass spectrometry for the quality control of therapeutic intact monoclonal antibodies. Journal of Chromatography A. 2019 ; DOI : 10.1016/j.chroma.2019.05.050

Book chapters

• Yoo Y.E., Smadja C., Ammar M, “Micro/Nano Fabrication and Packaging Technologies for Bio Systems” (Chap 3), In Engineering of Micro/Nano Biosystems: Fundamentals and Applications Ed Springer, 2020
• François Y.N., Marie A-L., Ruel C., Gahoual R., Tran N.T., Taverna M., “Capillary electrophoresis coupled to mass spectrometry as a powerful tool to investigate heterogeneities, conformers and oligomers of intact proteins” (chap 5) In Advances in Chromatography series (Vol. 56), Ed Taylor & Francis, 2019
• Marie A-L., Rouby G., Jaccoulet E., Smadja C., Tran N.T., Taverna M. “Capillary electrophoresis for the quality control of intact theraoeutic Monoclonal antibodies” (chapter 9, 40 pages) In capillary electrophoresis: trends abd development in pharmaceutical Research, Ed Pan Stanford, 2017
• Marie A-L., Tran N.T., Taverna M., “Characterization of Chemical and Physical Modifications of Human Serum Albumin by Capillary Zone Electrophoresis” in Capillary Electrophoresis of Proteins and Peptides: Methods and Protocols, Springer Protocols, Methods in Molecular Biology 1466, 2016.
• Jaccoulet E., Smadja C., Taverna M., “Quality Control of Therapeutic Monoclonal Antibodies at the Hospital After Their Compounding and Before Their Administration to Patients” in Capillary Electrophoresis of Proteins and Peptides: Methods and Protocols, Springer Protocols, Methods in Molecular Biology 1466, 2016.

Edition of Books

“Capillary Electrophoresis of proteins and peptides” in Methods in Molecular Biology series, Methods and protocols, Tran N.T., Taverna M. (Eds), 2016, vol 1466

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