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Microfluidique 3D et actionneurs magnétiques : de leur intégration à la préparation d'échantillons biologiques

Marc Fouet 1
1 LAAS-MILE - Équipe Micro-Nanofluidique pour les sciences de la vie et de l’environnement
LAAS - Laboratoire d'analyse et d'architecture des systèmes
Abstract : Microfluidic chips are key elements for solutions and biological samples handling and analysis. They are enablers for micro-scale studies and are the cornerstone of lab on chips, at the cutting edge of medical diagnostics. The aim of this thesis work was to explore functional possibilities offered by 3D microfluidic architectures for the development of diagnostic tools relying on cell sorting, tagging and handling. These functions were investigated on monocytes sub-populations, which are markers for many inflammatory diseases. In order to cover a consistent series of necessary steps for complex biological samples pretreatment, three additional functions were studied: size sorting with hydrodynamic filtration, immuno-isolation by magnetic separation, and on-chip tagging with magnetic microparticles. To perform tagging reactions, a micromixer based on diffusion and flow split and recombination (baker's transform) was fabricated and characterized. Analytical (diffusion) and numerical (diffusion-advection) models are showed, together with test experiments on the devices for mixing reactions of fluorescein/water and cells/microbeads. New approaches of hydrodynamic filtration based size sorting were investigated by devising 3D bypass structures, that allow developing a mixing strategy (tagging reactions) suited to cells and particles. An analytical model for flows and sorting efficiency is introduced and compared to the devices characterization. Furthermore, it was shown that this approach also enables sorting of sub-micron particles (like blood microparticles). All 3D microfluidic systems were obtained thanks to an original dry film photoresist stacking (lamination) technique, dramatically reducing micro-fabrication time, even though compatible with standard process. This fabrication technique also enables magnetic micro-sources integration in lab on chips by realizing planar micro-coils underneath microfluidic channels. By coupling the effects of integrated micro-coils to the fields generated by external magnets, we brought the proof of concept of systems dedicated to trapping, focusing and separating (in flow) magnetic microbeads. Models (magnetic fields and forces) are described along with devices characterization. Conception of specific instrumentation (current source) for micro-coils actuation is also shown, as it allows time and intensity control over applied magnetic fields.
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Marc Fouet. Microfluidique 3D et actionneurs magnétiques : de leur intégration à la préparation d'échantillons biologiques. Micro et nanotechnologies/Microélectronique. Université Paul Sabatier - Toulouse III, 2016. Français. ⟨NNT : 2016TOU30036⟩. ⟨tel-01355777v2⟩

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