Ces travaux de recherche s'intéressent à la caractérisation des transferts thermiques dans les milieux fluide-particules, et en particulier, les lits fluidisés au sein desquels un solide divisé est mis en suspension par un fluide. La grande diversité d'échelles spatiales et temporelles dans ces procédés nécessite d'étudier les interactions hydrodynamiques, thermiques et/ou chimiques entre les particules et le fluide à l'aide d'une approche multi-échelles. Une étude des transferts thermiques dans des lits fixes puis fluidisés, est réalisée à deux échelles : locale (Particle Resolved Simulation) et moyennée (Discrete Element Method-Computional Fluids Dynamics). L'étude PRS permet de caractériser les couplages locaux des transferts thermiques entre particules ainsi que la dynamique de ces transferts dans les configurations fluidisées. Une étude comparative entre les échelles met en évidence les limites du modèle DEM-CFD à capter les fluctuations des transferts thermiques observées dans les simulations PRS. Dans un dernier temps, les fermetures du modèle DEM-CFD sont améliorées de manière à réintroduire les fluctuations perdues par le changement d'échelles. / This work aims at characterizing heat transfer into fluid-solid flows, and more particularly fluidized beds, into which a solid phase is suspended by a flowing fluid. The wide range of spatial and temporal scales present in such processes encourage to study hydrodynamic, thermal and/or chemical interactions between the particles and the fluid through a multi-scale strategy. The analysis of thermal interactions was first carried out for fixed bed configurations and then, fluidized beds at two overlapping scales: local (PRS; Particle Resolved Simulation) and mesoscopic (DEMCFD; Discrete Element Method-Computional Fluids Dynamics). The PRS approach accounts for the local coupling of heat transfer between the particles and its dynamics into fluidized beds. A comparative study of the two scales indicated the limits of the DEM-CFD model to capture the heat transfer fluctuations observed into PRS. In a last step, the closure laws for DEM-CFD were improved to reintroduce the fluctuations lost at this scale.

Multiphase flows are a common phenomenon. Rains, sediment transport in rivers, snow and dust storms, mud slides and avalanches are examples of multiphase flows occurring in nature. Blood flow is an example of multiphase flow in the human body, which is of vital importance for survival. Multiphase flows occur widely in industrial applications from hydrocarbon extrac-tion to fuel combustion in engines, from spray painting to spray drying, evaporators, pumps and pneumatic conveying. Predicting multiphase flows is of vital importance to understand natural phenomenon and to design and improve industrial processes. Separated flows and dispersed flows are two types of multiphase flows, which occur together in many industrial applications. Physical features of these two classes are different and the transition from one to another involves complex flow physics. Experimental studies of multiphase flows are not easy, as most real world phenomenon cannot be scaled down to laboratory models. Even for those phenomenon that can be demonstrated at lab-oratory scale, rescaling to real world applications requires mathematical models. There are many challenges in experimental measurements of multiphase flows as well. Measurement techniques well suited for single phase flows have constraints when measuring multiphase phenomenon. Un-certainty in experimental measurements poses considerable difficulties in validating numerical models developed for predicting these flows. Owing to the computational effort required, direct simulation of multiphase flows, even for small scale real world applications is out of present scope. Numerical methods have been developed for dealing with each class of flow separately, that in-volves use of models for phenomenon that is computationally demanding. Reynolds Averaged Navier-Stokes (RANS) methods for predicting multiphase flows place strong requirements on turbulence models, as information about fluctuating quantities in the field, that have significant effects on dispersed phase, is not available. Large Eddy Simulation (LES) gives better predictions than RANS as the instantaneous field data is available and large scale unsteadiness that effects the dispersed phase can be captured. Recent LES studies of multiphase flows showed that the sub-grid-scale (SGS) model used for the continuous phase has an effect on the evolution of the dispersed phase. In this work, LES of multiphase flows is performed using Explicit Filtering Large Eddy Sim-ulation method. In this method, spatial derivatives are computed using higher order compact schemes that have spectral-like resolution. SGS modeling is provided by the use of a filter with smoothly falling transfer function. This method is mathematically consistent and converges to a DNS as the grid is refined. It has been successfully applied to combustion and aero-acoustics and this work is the first application of the method to multiphase flows. Study of dispersed multiphase flows was carried out in this work. Modeling of the dispersed phase is kept simple since the in-tention was to evaluate the capability of explicit filtering LES method in predicting multiphase flows. Continuous phase is solved using a compressible formulation with explicit filtering method. Spatial derivatives are computed using fourth and sixth order compact schemes that use derivative splitting method proposed by Hixon & Turkel (2000a) and second order Runge-Kutta (RK2) time stepping. The grid is stretched as needed. Non-reflecting boundary conditions due to Poinsot & Lele (1992) are used to avoid acoustic reflections from boundaries. Buffer zones (Bogey & Bailly (2002)) are employed at outflow and lateral boundaries to damp vortical structures. The code developed for continuous phase is evaluated by studying round jets at Re =36,000 and comparing with experimental measurements of Hussein et al. (1994) and Panchapakesan & Lumley (1993). Simulations showed excellent agreement with experimental results. Rate of decay of axial velocity and the evolution of turbulence intensities on the centerline matched very well with measurements. Radial profiles of mean and fluctuating components of velocities exhibit self-similarity. A set of studies were then performed using this code to assess the effect of numerical scheme, grid refinement & stretching and simulation times on the predictions. Results from these simulations showed good agreements with experiments and established the code for use in multiphase flows under various simulation conditions. To assess the prediction of multiphase flows using this LES method, an evaporating spray ex-periment by Chen et al. (2006) was simulated. The experiment uses a nebuliser for generating a finely atomized spray of acetone, which avoids complex breakdown phenomenon associated with air blast atomizers and provides well defined boundary conditions for model evaluation. The neb-uliser sits upstream in a pipe carrying air and droplets travel along with air for a distance of 10 diameters before exiting into a wind tunnel with co-flowing air. Droplet breakdown, if any, takes place inside the pipe and the spray is finely atomized by the time it reaches pipe exit. One of the experimental cases at Re =31,600, with a mass loading of 1.1% and a jet velocity of 56 m/s is simulated. Particle size has a χsquared distribution with a Sauter mean diameter of 18µm. In the self-similar region, decay of centerline velocity and turbulence intensities matched well with ex-perimental results. Continuous phase exhibits self-similar behavior. A series of simulations were then performed to match the initial region of the spray by altering the inflow conditions in the sim-ulation. Simulation that matched the breakdown location of the experiment revealed the presence of a relaxation zone with a higher initial spreading rate, followed by a lower asymptotic spreading rate. Studies were performed to understand the effect of various phenomenon like evaporation and droplet size on this behavior. A study of breakdown region of particle-laden jets was performed to understand the presence of relaxation zone post breakdown. Flow conditions were similar to evaporating spray experiment except that particles do not evaporate, mass loading is 2% and jet Reynolds number Re =2000. A series of grid refinements were performed and on the largest grid, gird spacing Δy =7.5η, where ηis an estimate of the Kolmogorov length scale based on flow conditions. Decay of axial velocity on the centerline showed variations with grid refinement, tending to the experimentally measured value as the grid is refined. Variation of turbulence intensities along the centerline revealed a jump in axial velocity fluctuations at the breakdown location, while radial and azimuthal velocities showed a smooth increase to their asymptotic value. This jump was resolved on grid refinement and on fine grids axial velocity fluctuations followed the other two quantities closely in their rise to asymptotic state. Comparison of these quantities with a jet without particles revealed that the flow features are same for a jet with and without particles, and at the mass loading studied, particles have negligible effect on jet breakdown. Another study performed at a higher Reynolds number of Re =11,000, under similar flow conditions showed similar behavior. To assess the ability of predicting dispersed phase, simulations of particle-laden flows at low Stokes number were performed and compared against an experiment by Lau & Nathan (2014). The experiment studies variation of velocity and particle concentration along the centerline, and half widths of a jet velocity and concentration. Particles are injected into a pipe along with air, and the two phase flow is fully developed by the time it exits the pipe into a wind tunnel along with a co-flow. Particles are mono-disperse with a density of 1200 kg/m3. Mass loading is 40% so that particles have a significant effect on the continuous phase. Two cases at particle Stokes number of 1.4, one with Re =10,000, bulk velocity of 12 m/s and particle diameter of 20µm and another with Re =22,500, bulk velocity of 36 m/s and particle diameter of 10µm were simulated. Simulations of both the cases showed good match with experimental measurements of centerline decay for the continuous phase. For the dispersed case, simulations with larger particles showed good match with experimental results, while smaller particles showed differences. This was understood to be the effect of lateral migration which is prominent in case of smaller particles, the models for which have not been used in the present simulation study.

Le système immunitaire adaptatif joue un rôle de premier plan dans la défense contre les infections. La réponse humorale, impliquant la production d'anticorps, est un élément important de la réponse immunitaire adaptative. Au cours d'une infection, des cellules B spécifiques du système immunitaire prolifèrent et libèrent de grandes quantités d'anticorps qui se lient sélectivement à la protéine cible (antigène) trouvée sur le pathogène invasif, induisant la destruction du pathogène.Cependant, le système immunitaire ne répond pas toujours suffisamment efficacement pour détruire les agents pathogènes, et les mécanismes de tolérance empêchent la génération d'anticorps contre les protéines humaines - comme les marqueurs de surface cellulaire sur les cellules cancéreuses ou les cytokines impliquées dans des maladies inflammatoires et auto-immunes - qui pourraient être des cibles thérapeutiques importantes. Par conséquent, il existe un grand intérêt pour la recherche et le développement d'anticorps spécifiques qui peuvent être utilisés pour le traitement des patients par immunothérapie. En raison de leur grande affinité et de leur liaison sélective aux antigènes, les anticorps monoclonaux (mAbs) sont apparus comme des agents thérapeutiques puissants. Les anticorps monoclonaux dérivés de cellules B individuelles ont une séquence unique et présentent une affinité de liaison pour un antigène spécifique. Cependant, jusqu'à maintenant, la découverte des mAbs a été limitée par l'absence de méthodes à haut débit pour le criblage direct et à grande échelle de cellules B primaires non immortalisées pour découvrir les rares cellules B qui produisent des anticorps spécifiques d'intérêt clinique. Ceci est maintenant possible avec l'émergence et l'amélioration des méthodes de compartimentation in vitro pour l'encapsulation et le criblage de cellules uniques dans des gouttelettes picolitriques. Dans mon projet de doctorat, je décris le développement d'immunodosages et de dispositifs microfluidiques pour le criblage phénotypique direct de cellules individuelles à partir de populations de cellules B enrichies. Ce développement a permis une analyse détaillée de la réponse immunitaire humorale, avec une résolution à l’échelle de la cellule unique. C’est aussi un élément essentiel d'un pipeline de détection d'anticorps couplant le criblage phénotypique de cellules individuelles au séquençage d'anticorps sur cellules uniques. Il est maintenant possible, pour la première fois, de cribler des millions de cellules B individuelles en fonction de l'activité de liaison des anticorps sécrétés et de récupérer les séquences d'anticorps / The adaptive immune system plays a leading role in defense against infection. The humoral response, involving the production of antibodies, is an important component of the adaptive immune response. During an infection, specific B cells of the immune system proliferate and release large amounts of antibodies which bind selectively to the target protein (antigen) found on the invading pathogen, inducing destruction of the pathogen. However, the immune system does not always respond efficiently enough to destroy pathogens, and tolerance mechanisms prevent the generation of antibodies against human protein - such as cell surface markers on cancer cells or cytokines involved in inflammatory and autoimmune disease - that could be important therapeutic targets. Hence, there is great interest in research and development of specific antibodies that can be used for immunotherapy of patients. Due to their high affinity and selective binding to antigens, monoclonal antibodies (mAbs) have emerged as powerful therapeutic agents. Monoclonal antibodies derived from single B cells have a unique sequence and display binding affinity for a specific antigen. However, until now, the discovery of mAbs has been limited by the lack of high-throughput methods for the direct and large-scale screening of non-immortalized primary B cells to uncover rare B cells which produce the specific antibodies of clinical interest. This is now becoming possible with the emergence and improvement of in vitro compartmentalization methods for single-cell encapsulation and screening in picoliter droplets. In my PhD project, I describe the development of binding immunoassays and microfluidic devices for the direct phenotypic screening of single-cells from enriched B cell populations. This development has enabled detailed analysis of the humoral immune response, with single-cell resolution and is an essential component of an antibody-discovery pipeline coupling single-cell phenotypic screening to single-cell antibody sequencing. It is now possible, for the first time, to screen millions of single B cells based on the binding activity of the secreted antibodies and to recover the antibody sequences