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Coronavirus disease 2019 (COVID-19) is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and can affect multiple organs, among which is the circulatory system. Inflammation and mortality risk markers were previously detected in COVID-19 plasma and red blood cells (RBCs) metabolic and proteomic profiles. Additionally, biophysical properties, such as deformability, were found to be changed during the infection. Based on such data, we aim to better characterize RBC functions in COVID-19. We evaluate the flow properties of RBCs in severe COVID-19 patients admitted to the intensive care unit by using microfluidic techniques and automated methods, including artificial neural networks, for an unbiased RBC analysis. We find strong flow and RBC shape impairment in COVID-19 samples and demonstrate that such changes are reversible upon suspension of COVID-19 RBCs in healthy plasma. Vice versa, healthy RBCs resemble COVID-19 RBCs when suspended in COVID-19 plasma. Proteomics and metabolomics analyses allow us to detect the effect of plasma exchanges on both plasma and RBCs and demonstrate a new role of RBCs in maintaining plasma equilibria at the expense of their flow properties. Our findings provide a framework for further investigations of clinical relevance for therapies against COVID-19 and possibly other infectious diseases.

Coronavirus disease 2019 (COVID-19) is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and can affect multiple organs, among which is the circulatory system. Inflammation and mortality risk markers were previously detected in COVID-19 plasma and red blood cells (RBCs) metabolic and proteomic profiles. Additionally, biophysical properties, such as deformability, were found to be changed during the infection. Based on such data, we aim to better characterize RBC functions in COVID-19. We evaluate the flow properties of RBCs in severe COVID-19 patients admitted to the intensive care unit by using microfluidic techniques and automated methods, including artificial neural networks, for an unbiased RBC analysis. We find strong flow and RBC shape impairment in COVID-19 samples and demonstrate that such changes are reversible upon suspension of COVID-19 RBCs in healthy plasma. Vice versa, healthy RBCs resemble COVID-19 RBCs when suspended in COVID-19 plasma. Proteomics and metabolomics analyses allow us to detect the effect of plasma exchanges on both plasma and RBCs and demonstrate a new role of RBCs in maintaining plasma equilibria at the expense of their flow properties. Our findings provide a framework for further investigations of clinical relevance for therapies against COVID-19 and possibly other infectious diseases.

Ligand receptor based adhesion is the primary mode of interaction of cellular blood constituents with the endothelium. These adhered entities also experience shear flow imposed by the blood which may lead to their detachment due to the viscous lift forces. Here, we have studied the role of the ligand-receptor bond kinetics in the detachment of an adhered vesicle (a simplified cell model) under shear flow. Using boundary integral formulation we performed numerical simulation of a two dimensional vesicle under shear flow for different values of applied shear rates and time scale of bond kinetics. We observe that the vesicle demonstrates three steady state configurations-adhered, pinned and detached for fast enough ligand-receptor kinetics (akin to Lennard-Jones adhesion). However, for slow bond kinetics the pinned state is not observed. We present scaling laws for the critical shear rates corresponding to the transitions among these three states. These results can help with identifying the processes of cell adhesion/detachment in the blood stream, prevalent features during the immune response and cancer metastasis. This journal is © The Royal Society of Chemistry.

Ligand receptor based adhesion is the primary mode of interaction of cellular blood constituents with the endothelium. These adhered entities also experience shear flow imposed by the blood which may lead to their detachment due to the viscous lift forces. Here, we have studied the role of the ligand-receptor bond kinetics in the detachment of an adhered vesicle (a simplified cell model) under shear flow. Using boundary integral formulation we performed numerical simulation of a two dimensional vesicle under shear flow for different values of applied shear rates and time scale of bond kinetics. We observe that the vesicle demonstrates three steady state configurations-adhered, pinned and detached for fast enough ligand-receptor kinetics (akin to Lennard-Jones adhesion). However, for slow bond kinetics the pinned state is not observed. We present scaling laws for the critical shear rates corresponding to the transitions among these three states. These results can help with identifying the processes of cell adhesion/detachment in the blood stream, prevalent features during the immune response and cancer metastasis. This journal is © The Royal Society of Chemistry.

Ligand receptor based adhesion is the primary mode of interaction of cellular blood constituents with the endothelium. These adhered entities also experience shear flow imposed by the blood which may lead to their detachment due to the viscous lift forces. Here, we have studied the role of the ligand-receptor bond kinetics in the detachment of an adhered vesicle (a simplified cell model) under shear flow. Using boundary integral formulation we performed numerical simulation of a two dimensional vesicle under shear flow for different values of applied shear rates and time scale of bond kinetics. We observe that the vesicle demonstrates three steady state configurations-adhered, pinned and detached for fast enough ligand-receptor kinetics (akin to Lennard-Jones adhesion). However, for slow bond kinetics the pinned state is not observed. We present scaling laws for the critical shear rates corresponding to the transitions among these three states. These results can help with identifying the processes of cell adhesion/detachment in the blood stream, prevalent features during the immune response and cancer metastasis. This journal is © The Royal Society of Chemistry.

Ligand receptor based adhesion is the primary mode of interaction of cellular blood constituents with the endothelium. These adhered entities also experience shear flow imposed by the blood which may lead to their detachment due to the viscous lift forces. Here, we have studied the role of the ligand-receptor bond kinetics in the detachment of an adhered vesicle (a simplified cell model) under shear flow. Using boundary integral formulation we performed numerical simulation of a two dimensional vesicle under shear flow for different values of applied shear rates and time scale of bond kinetics. We observe that the vesicle demonstrates three steady state configurations-adhered, pinned and detached for fast enough ligand-receptor kinetics (akin to Lennard-Jones adhesion). However, for slow bond kinetics the pinned state is not observed. We present scaling laws for the critical shear rates corresponding to the transitions among these three states. These results can help with identifying the processes of cell adhesion/detachment in the blood stream, prevalent features during the immune response and cancer metastasis. This journal is © The Royal Society of Chemistry.

Driven or active suspensions can display fascinating collective behavior, where coherent motions or structures arise on a scale much larger than that of the constituent particles. Here, we report numerical simulations and an analytical model revealing that deformable particles and, in particular, red blood cells (RBCs) assemble into regular patterns in a confined shear flow. The pattern wavelength concurs well with our experimental observations. The order is of a pure hydrodynamic and inertialess origin, and it emerges from a subtle interplay between (i) hydrodynamic repulsion by the bounding walls that drives deformable cells towards the channel midplane and (ii) intercellular hydrodynamic interactions that can be attractive or repulsive depending on cell-cell separation. Various crystal-like structures arise depending on the RBC concentration and confinement. Hardened RBCs in experiments and rigid particles in simulations remain disordered under the same conditions where deformable RBCs form regular patterns, highlighting the intimate link between particle deformability and the emergence of order.

Flux of rigid or soft particles (such as drops, vesicles, red blood cells, etc.) in a channel is a complex function of particle concentration, which depends on the details of induced dissipation and suspension structure due to hydrodynamic interactions with walls or between neighboring particles. Through two-dimensional and three-dimensional simulations and a simple model that reveals the contribution of the main characteristics of the flowing suspension, we discuss the existence of an optimal volume fraction for cell transport and its dependence on the cell mechanical properties. The example of blood is explored in detail, by adopting the commonly used modeling of red blood cells dynamics. We highlight the complexity of optimization at the level of a network, due to the antagonist evolution of local volume fraction and optimal volume fraction with the channels diameter. In the case of the blood network, the most recent results on the size evolution of vessels along the circulatory network of healthy organs suggest that the red blood cell volume fraction (hematocrit) of healthy subjects is close to optimality, as far as transport only is concerned. However, the hematocrit value of patients suffering from diverse red blood cel pathologies may strongly deviate from optimality.

Driven or active suspensions can display fascinating collective behavior, where coherent motions or structures arise on a scale much larger than that of the constituent particles. Here, we report numerical simulations and an analytical model revealing that deformable particles and, in particular, red blood cells (RBCs) assemble into regular patterns in a confined shear flow. The pattern wavelength concurs well with our experimental observations. The order is of a pure hydrodynamic and inertialess origin, and it emerges from a subtle interplay between (i) hydrodynamic repulsion by the bounding walls that drives deformable cells towards the channel midplane and (ii) intercellular hydrodynamic interactions that can be attractive or repulsive depending on cell-cell separation. Various crystal-like structures arise depending on the RBC concentration and confinement. Hardened RBCs in experiments and rigid particles in simulations remain disordered under the same conditions where deformable RBCs form regular patterns, highlighting the intimate link between particle deformability and the emergence of order.

Flux of rigid or soft particles (such as drops, vesicles, red blood cells, etc.) in a channel is a complex function of particle concentration, which depends on the details of induced dissipation and suspension structure due to hydrodynamic interactions with walls or between neighboring particles. Through two-dimensional and three-dimensional simulations and a simple model that reveals the contribution of the main characteristics of the flowing suspension, we discuss the existence of an optimal volume fraction for cell transport and its dependence on the cell mechanical properties. The example of blood is explored in detail, by adopting the commonly used modeling of red blood cells dynamics. We highlight the complexity of optimization at the level of a network, due to the antagonist evolution of local volume fraction and optimal volume fraction with the channels diameter. In the case of the blood network, the most recent results on the size evolution of vessels along the circulatory network of healthy organs suggest that the red blood cell volume fraction (hematocrit) of healthy subjects is close to optimality, as far as transport only is concerned. However, the hematocrit value of patients suffering from diverse red blood cel pathologies may strongly deviate from optimality.

The absence of gravity during space flight can alter cardio-vascular functions partially due to reduced physical activity. This affects the overall hemodynamics, and in particular the level of shear stresses to which blood vessels are submitted. Long-term exposure to space environment is thus susceptible to induce vascular remodeling through a mechanotransduction cascade that couples vessel shape and function with the mechanical cues exerted by the circulating cells on the vessel walls. Central to such processes, the glycocalyx – i.e. the micron-thick layer of biomacromolecules that lines the lumen of blood vessels and is directly exposed to blood flow – is a major actor in the regulation of biochemical and mechanical interactions. We discuss in this article several experiments performed under microgravity, such as the determination of lift force and collective motion in blood flow, and some preliminary results obtained in artificial microfluidic circuits functionalized with endothelium that offer interesting perspectives for the study of the interactions between blood and endothelium in healthy condition as well as by mimicking the degradation of glycocalyx caused by long space missions. A direct comparison between experiments and simulations is discussed., SCOPUS: sh.j, info:eu-repo/semantics/published

info:eu-repo/semantics/published

The behaviour of a vesicle suspension in a simple shear flow between plates (Couette flow) was investigated experimentally in parabolic flight and sounding rocket experiments by Digital Holographic Microscopy. The lift force which pushes deformable vesicles away from walls was quantitatively investigated and is found to be rather well described by a theoretical model by Olla (J Phys II (France) 7:1533, 1997). At longer shearing times, vesicles reach a steady distribution about the center plane of the shear flow chamber, through a balance between the lift force and shear induced diffusion due to hydrodynamic interactions between vesicles. This steady distribution was investigated in the BIOMICS experiment in the MASER 11 sounding rocket. The results allow an estimation of self-diffusion coefficients in vesicle suspensions and reveal possible segregation phenomena in polydisperse suspensions. © 2010 Springer Science+Business Media B.V., SCOPUS: ar.j, info:eu-repo/semantics/published

The behaviour of a vesicle suspension in a simple shear flow between plates (Couette flow) was investigated experimentally in parabolic flight and sounding rocket experiments by Digital Holographic Microscopy. The lift force which pushes deformable vesicles away from walls was quantitatively investigated and is found to be rather well described by a theoretical model by Olla (J Phys II (France) 7:1533, 1997). At longer shearing times, vesicles reach a steady distribution about the center plane of the shear flow chamber, through a balance between the lift force and shear induced diffusion due to hydrodynamic interactions between vesicles. This steady distribution was investigated in the BIOMICS experiment in the MASER 11 sounding rocket. The results allow an estimation of self-diffusion coefficients in vesicle suspensions and reveal possible segregation phenomena in polydisperse suspensions. © 2010 Springer Science+Business Media B.V., SCOPUS: ar.j, info:eu-repo/semantics/published

Lateral migration of vesicles (closed lipidic membranes) in a flow is characterized as a function of the relevant flow parameters and mechanical properties of the vesicles. We consider low Reynolds number flows, and migration is only due to viscous effects. Through experiments and simulations, we exhibit two different origins for such cross streamline migration: the presence of a wall, and a non-constant shear rate, as for instance in a Poiseuille flow. Such migration modifies the distribution of vesicles in a sheared polydisperse suspension; we present preliminary results proving that the hydrodynamic interactions between vesicles greatly modify the distribution of vesicles according to their sizes and deflation. © 2009 Materials Research Society., SCOPUS: cp.p, info:eu-repo/semantics/published

Lateral migration of vesicles (closed lipidic membranes) in a flow is characterized as a function of the relevant flow parameters and mechanical properties of the vesicles. We consider low Reynolds number flows, and migration is only due to viscous effects. Through experiments and simulations, we exhibit two different origins for such cross streamline migration: the presence of a wall, and a non-constant shear rate, as for instance in a Poiseuille flow. Such migration modifies the distribution of vesicles in a sheared polydisperse suspension; we present preliminary results proving that the hydrodynamic interactions between vesicles greatly modify the distribution of vesicles according to their sizes and deflation. © 2009 Materials Research Society., SCOPUS: cp.p, info:eu-repo/semantics/published

Lateral migration of vesicles (closed lipidic membranes) in a flow is characterized as a function of the relevant flow parameters and mechanical properties of the vesicles. We consider low Reynolds number flows, and migration is only due to viscous effects. Through experiments and simulations, we exhibit two different origins for such cross streamline migration: the presence of a wall, and a non-constant shear rate, as for instance in a Poiseuille flow. Such migration modifies the distribution of vesicles in a sheared polydisperse suspension; we present preliminary results proving that the hydrodynamic interactions between vesicles greatly modify the distribution of vesicles according to their sizes and deflation. © 2009 Materials Research Society., SCOPUS: cp.p, info:eu-repo/semantics/published

Lateral migration of vesicles (closed lipidic membranes) in a flow is characterized as a function of the relevant flow parameters and mechanical properties of the vesicles. We consider low Reynolds number flows, and migration is only due to viscous effects. Through experiments and simulations, we exhibit two different origins for such cross streamline migration: the presence of a wall, and a non-constant shear rate, as for instance in a Poiseuille flow. Such migration modifies the distribution of vesicles in a sheared polydisperse suspension; we present preliminary results proving that the hydrodynamic interactions between vesicles greatly modify the distribution of vesicles according to their sizes and deflation. © 2009 Materials Research Society., SCOPUS: cp.p, info:eu-repo/semantics/published

Lateral migration of vesicles (closed lipidic membranes) in a flow is characterized as a function of the relevant flow parameters and mechanical properties of the vesicles. We consider low Reynolds number flows, and migration is only due to viscous effects. Through experiments and simulations, we exhibit two different origins for such cross streamline migration: the presence of a wall, and a non-constant shear rate, as for instance in a Poiseuille flow. Such migration modifies the distribution of vesicles in a sheared polydisperse suspension; we present preliminary results proving that the hydrodynamic interactions between vesicles greatly modify the distribution of vesicles according to their sizes and deflation. © 2009 Materials Research Society., SCOPUS: cp.p, info:eu-repo/semantics/published

Lateral migration of vesicles (closed lipidic membranes) in a flow is characterized as a function of the relevant flow parameters and mechanical properties of the vesicles. We consider low Reynolds number flows, and migration is only due to viscous effects. Through experiments and simulations, we exhibit two different origins for such cross streamline migration: the presence of a wall, and a non-constant shear rate, as for instance in a Poiseuille flow. Such migration modifies the distribution of vesicles in a sheared polydisperse suspension; we present preliminary results proving that the hydrodynamic interactions between vesicles greatly modify the distribution of vesicles according to their sizes and deflation. © 2009 Materials Research Society., SCOPUS: cp.p, info:eu-repo/semantics/published

Lateral migration of vesicles (closed lipidic membranes) in a flow is characterized as a function of the relevant flow parameters and mechanical properties of the vesicles. We consider low Reynolds number flows, and migration is only due to viscous effects. Through experiments and simulations, we exhibit two different origins for such cross streamline migration: the presence of a wall, and a non-constant shear rate, as for instance in a Poiseuille flow. Such migration modifies the distribution of vesicles in a sheared polydisperse suspension; we present preliminary results proving that the hydrodynamic interactions between vesicles greatly modify the distribution of vesicles according to their sizes and deflation. © 2009 Materials Research Society., SCOPUS: cp.p, info:eu-repo/semantics/published

Lateral migration of vesicles (closed lipidic membranes) in a flow is characterized as a function of the relevant flow parameters and mechanical properties of the vesicles. We consider low Reynolds number flows, and migration is only due to viscous effects. Through experiments and simulations, we exhibit two different origins for such cross streamline migration: the presence of a wall, and a non-constant shear rate, as for instance in a Poiseuille flow. Such migration modifies the distribution of vesicles in a sheared polydisperse suspension; we present preliminary results proving that the hydrodynamic interactions between vesicles greatly modify the distribution of vesicles according to their sizes and deflation. © 2009 Materials Research Society., SCOPUS: cp.p, info:eu-repo/semantics/published

SCOPUS: cp.p, info:eu-repo/semantics/published

SCOPUS: cp.p, info:eu-repo/semantics/published

Cette thèse expérimentale s’inscrit dans le domaine des sciences séparatives et se base sur la technique de SPLITT (SPLIT-flow Thin fractionation). Son objectif consiste en l’étude des mécanismes qui sont à l’origine de la séparation, en continu et sans membrane, d’objets de taille micrométrique dans des mini-séparateurs fluidiques (Step-SPLITT). Les expériences menées, en laboratoire et lors de vols paraboliques, ont révélé le couplage complexe comme l’influence des effets hydrodynamiques et du champ gravitationnel sur la migration transverse des espèces en écoulement. Des visualisations tridimensionnelles par holographie digitale ont corroboré nos résultats et dévoilé des comportements inattendus. Les capacités séparatives des Step-SPLITT ont rendu possible l’analyse et la séparation d’objets biologiques et biomimétiques. Enfin, cette étude complétée par une modélisation tridimensionnelle de l’écoulement nous a permis de mettre au point un nouveau prototype de séparateur.This experimental thesis belongs to the field of separative sciences and is based on the SPLITT technique (SPLIT-flow Thin fractionation). The objective is to study the mechanisms that are at the origin of continuous and membraneless separation of micron-size species in mini fluidic separators (Step-SPLITT). Experiments undertaken in laboratory and during parabolic flights revealed the complex coupling of the hydrodynamic effects and the gravitational field influencing the transverse migration of the flowing species. Three-dimensional visualizations performed by digital holography confirmed our results and disclosed unexpected behaviours. The separation capacities of Step-SPLITT made the analysis and the separation of biological and biomimetic species possible. In addition this study in conjunction with a three-dimensional flow modelling enabled us to develop a new prototype of separator., Doctorat en sciences appliquées, info:eu-repo/semantics/nonPublished

Cette thèse expérimentale s’inscrit dans le domaine des sciences séparatives et se base sur la technique de SPLITT (SPLIT-flow Thin fractionation). Son objectif consiste en l’étude des mécanismes qui sont à l’origine de la séparation, en continu et sans membrane, d’objets de taille micrométrique dans des mini-séparateurs fluidiques (Step-SPLITT). Les expériences menées, en laboratoire et lors de vols paraboliques, ont révélé le couplage complexe comme l’influence des effets hydrodynamiques et du champ gravitationnel sur la migration transverse des espèces en écoulement. Des visualisations tridimensionnelles par holographie digitale ont corroboré nos résultats et dévoilé des comportements inattendus. Les capacités séparatives des Step-SPLITT ont rendu possible l’analyse et la séparation d’objets biologiques et biomimétiques. Enfin, cette étude complétée par une modélisation tridimensionnelle de l’écoulement nous a permis de mettre au point un nouveau prototype de séparateur.This experimental thesis belongs to the field of separative sciences and is based on the SPLITT technique (SPLIT-flow Thin fractionation). The objective is to study the mechanisms that are at the origin of continuous and membraneless separation of micron-size species in mini fluidic separators (Step-SPLITT). Experiments undertaken in laboratory and during parabolic flights revealed the complex coupling of the hydrodynamic effects and the gravitational field influencing the transverse migration of the flowing species. Three-dimensional visualizations performed by digital holography confirmed our results and disclosed unexpected behaviours. The separation capacities of Step-SPLITT made the analysis and the separation of biological and biomimetic species possible. In addition this study in conjunction with a three-dimensional flow modelling enabled us to develop a new prototype of separator., Doctorat en sciences appliquées, info:eu-repo/semantics/nonPublished