### An integrated detection method for flow viscosity measurements in microdevices

### Normalization of blood viscosity according to the hematocrit and the biomechanical properties of red blood cells

### The long cross-over dynamics of capillary imbibition

### A biomechanical strategy to control bacterial proliferation

### Fluid front advance in hydrophilic structured micro channels

### The dynamics of shapes of vesicles membranes with time dependent spontaneous curvature

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We study the time evolution of the shape of a vesicle membrane under time-dependent spontaneous curvature by means of phase-field model. We introduce the variation in time of the spontaneous curvature via a second field which represents the concentration of a substance that anchors with the lipid bilayer thus changing the local curvature and producing constriction. This constriction is mediated by the action on the membrane of an structure resembling the role of a Z ring. Our phase-field model is able to reproduce a number of different shapes that have been experimentally observed. Different shapes are associated with different constraints imposed upon the model regarding conservation of membrane area. In particular, we show that if area is conserved our model reproduces the so-called L-form shape. By contrast, if the area of the membrane is allowed to grow, our model reproduces the formation of a septum in the vicinity of the constriction. Furthermore, we propose a new term in the free energy which allows the membrane to evolve towards eventual pinching.

### Coaxial flow focusing microfluidic devices: Experiments and theory

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A coaxial flow focusing PDMS (polydimethylsiloxane) microfluidic device has been designed and manufactured by soft lithography in order to experimentally study a miscible inner flow. We studied a coaxially focused inner flow (formed by an aqueous fluorescein solution) which was fully isolated from all microchannel surfaces by an additional water outer flow. Different flow rates were used to produce a variety of flow ratios and a 3D reconstruction of the cross-section was performed using confocal microscope images. The results showed an elliptical section of the coaxially focused inner flow that changes in shape depending on the flow rate ratio applied. We have also developed a mathematical model that allows us to predict and control the geometry of the coaxially focused inner flow.

### Enhanced imbibitions from cooperation between wetting and inertia via pulsatile forcing

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We study the dynamics of microfluidic interfaces driven by pulsatile pressures in the presence of neutral and hydrophilic walls. For this, we propose a new phase field model that takes inertia into account. For neutral wetting, the interface dynamics is characterized by a response function that depends on a non-dimensional frequency, which involves the time scale associated with inertia. We have found a regime, for large values of this non-dimensional frequency, in which inertia is relevant, and our model is necessary for a correct description of the dynamics. For hydrophilic walls, the dynamics of the contact line with pulsatile forcing is basically undistinguishable to the dynamics of imbibition solely due to wetting. However, we observe that the presence of inertia causes the interface to advance faster than in the absence of pulsatile forcing. This is because pulsatile forcing induces inertia at the bulk to cooperate with wetting creating an enhancement of the imbibition process. We characterize this complex dynamics with transitory exponents that, at early times, are larger than the Washburn ones, and tend to the Washburn exponent at long times, when the interface feels less and less the driving force applied at the entrance of the microchannel, and the dynamics is dominated solely by wetting.

### Collective behavior of red blood cells in confined channels

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We study the flow properties of red blood cells in confined channels, when the channel width is comparable to the cell size. We focus on the case of intermediate concentrations when hydrodynamic interactions between cells play a dominant role. This regime is different to the case of low concentration in which the cells behave as hydrodynamically isolated. In this last case, the dynamic behavior is entirely controlled by the interplay between the interaction with the wall and the elastic response of the cell membrane. Our results highlight the different fluid properties when collective flow is present. The cells acquire a characteristic slipper shape, and parachute shapes are only observed at very large capillary numbers. We have characterized the spatial ordering and the layering by means of a pairwise correlation function. Focusing effects are observed at the core of the channel instead of at the lateral position typical of the single-train case. These results indicate that at these intermediate concentrations we observed at the microscale the first steps of the well-known macroscopic Fahraeus-Lindqvist effect. The rheological properties of the suspension are studied by means of the effective viscosity, with an expected shear-thinning behavior. Two main differences are obtained with respect to the single-train case. First, a large magnitude of the viscosity is obtained indicating a high resistance to flow. Secondly, the shear-thinning behavior is obtained at larger values of the capillary number respect to the single-train case. These results suggest that the phenomena of ordering in space and orientation occur at higher values of the capillary number.

### Front Microrheology of Biological Fluids

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We present a study of front microrheology through the development of a microfluidic device and method that describes accurately the non-linear rheology of blood, by means of a simple optical detection method based on tracking the fluid-air interface moving inside a microchannel. We study the behavior of Newtonian fluids of different viscosities and densities, as well, we performed measures for blood at different red blood cells concentration and at different days from its extraction. We have developed a scaling method which allows us to determine a relation between the red blood cell properties at different days from its extraction, according to the agreggation properties of red blood cell. Our results have been compared with theoretical and bibliographical results, which shows realiable results with an error around 6%. In general, our device and method is usefull as a viscometer and rheometer, as well as, it enables to establish a relation between blood viscosity and its red blood cells characteristics.

### Front microrheology of the non-Newtonian behaviour of blood: scaling theory of erythrocyte aggregation by aging

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We introduce a new framework to study the non-Newtonian behaviour of fluids at the microscale based on the analysis of front advancement. We apply this methodology to study the non-linear rheology of blood in microchannels. We carry out experiments in which the non-linear viscosity of blood samples is quantified at different haematocrits and ages. Under these conditions, blood exhibits a power-law dependence on the shear rate. In order to analyse our experimental data, we put forward a scaling theory which allows us to define an adhesion scaling number. This theory yields a scaling behaviour of the viscosity expressed as a function of the adhesion capillary number. By applying this scaling theory to samples of different ages, we are able to quantify how the characteristic adhesion energy varies as time progresses. This connection between microscopic and mesoscopic properties allows us to estimate quantitatively the change in the cell–cell adhesion energies as the sample ages.

### Elastic and dynamic properties of membrane phase-field models

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Phase-field models have been extensively used to study interfacial phenomena, from solidification to vesicle dynamics. In this article, we analyze a phase-field model that captures the relevant physical features that characterize biological membranes. We show that the Helfrich theory of elasticity of membranes can be applied to phase-field models, allowing to derive the expressions of the stress tensor, lateral stress profile and elastic moduli. We discuss the relevance and interpretations of these magnitudes from a phase-field perspective. Taking the sharp-interface limit we show that the membrane macroscopic equilibrium equation can be derived from the equilibrium condition of the phase-field interface. We also study two dynamic models that describe the behaviour of a membrane. From the study of the relaxational behaviour of the membrane we characterize the relevant dynamics of each model, and discuss their applications.

### Capillary Filling at the Microscale: Control of Fluid Front Using Geometry

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We propose an experimental and theoretical framework for the study of capillary filling at the micro-scale. Our methodology enables us to control the fluid flow regime so that we can characterise properties of Newtonian fluids such as their viscosity. In particular, we study a viscous, non-inertial, non-Washburn regime in which the position of the fluid front increases linearly with time for the whole duration of the experiment. The operating shear-rate range of our apparatus extends over nearly two orders of magnitude. Further, we analyse the advancement of a fluid front within a microcapillary in a system of two immiscible Newtonian liquids. We observe a non-Washburn regime in which the front can accelerate or decelerate depending on the viscosity contrast between the two liquids. We then propose a theoretical model which enables us to study and explain both non-Washburn regimes. Furthermore, our theoretical model allows us to put forward ways to control the emergence of these regimes by means of geometrical parameters of the experimental set-up. Our methodology allows us to design and calibrate a micro-viscosimetre which works at constant pressure.

### Phase-field modelling of the dynamics of Z-ring formation in liposomes: Onset of constriction and coarsening

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We propose a model for the dynamics of the formation of rings of FtsZ on tubular liposomes which produce constriction on the corresponding membrane. Our phase-field model is based on a simple bending energy that captures the dynamics of the interplay between the protein and the membrane. The short-time regime is analyzed by a linear dispersion relation, with which we are able to predict the number of rings per unit length on a tubular liposome. We study numerically the long-time dynamics of the system in the non-linear regime where we observe coarsening of Z-rings on tubular liposomes. In particular, our numerical results show that, during the coarsening process, the number of Z-rings decreases as the radius of tubular liposome increases. This is consistent with the experimental observation that the separation between rings is proportional to the radius of the liposome. Our model predicts that the mechanism for the increased rate of coarsening in liposomes of larger radius is a consequence of the increased interface energy.

### Superconfinement tailors fluid flow at micro-scales

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Understanding fluid dynamics under extreme confinement, where device and intrinsic fluid length scales become comparable, is essential to successfully develop the coming generations of fluidic devices. Here we report measurements of advancing fluid fronts in such a regime, which we dub superconfinement. We find that the strong coupling between contact-line friction and geometric confinement gives rise to a new stability regime where the maximum speed for a stable moving front exhibits a distinctive response to changes in the bounding geometry. Unstable fronts develop into drop-emitting jets controlled by thermal fluctuations. Numerical simulations reveal that the dynamics in superconfined systems is dominated by interfacial forces. Henceforth, we present a theory that quantifies our experiments in terms of the relevant interfacial length-scale, which in our system is the intrinsic contact-line slip length. Our findings show that length-scale overlap can be used as a new fluid-control mechanism in strongly confined systems.

### Phase-field theories for mathematical modeling of biological membranes

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Biological membranes are complex structures whose mechanics are usually described at a mesoscopic level, such as the Helfrich bending theory. In this article, we present the phase-field methods, a useful tool for studying complex membrane problems which can be applied to very different phenomena. We start with an overview of the general theory of elasticity, paying special attention to its derivation from a molecular scale. We then study the particular case of membrane elasticity, explicitly obtaining the Helfrich bending energy. Within the framework of this theory, we derive a phase-field model for biological membranes and explore its physical basis and interpretation in terms of membrane elasticity. We finally explain three examples of applications of these methods to membrane related problems. First, the case of vesicle pearling and tubulation, when lipidic vesicles are exposed to the presence of hydrophobic polymers that anchor to the membrane, inducing a shape instability. Finally, we study the behavior of red blood cells while flowing in narrow microchannels, focusing on the importance of membrane elasticity to the cell flow capabilities.

### Dynamics of Z-ring formation in liposomes

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We propose a model for the dynamics of the formation of rings of FtsZ on tubular liposomes which produce constriction on the corresponding membrane. The main characteristic of our model is the energy of interaction between the FtsZ protein and the membrane. This coupling is achieved through the protein increasing the spontaneous curvature energy. Our analysis is based on a linear dispersion relation, valid in general in the linear, short-time regime, which allows us to estimate the minimum concentration of FtsZ protein in order to induce constriction. Using this dispersion relation we are also able to predict the effect of increasing membrane rigidity on the constriction process. Our model allows to study the non-linear, long- term dynamics of the system where we observe coarsening of Z-rings on tubular liposomes.

### Rheology of red blood cells under flow in higly confined microchannels: II. Effect of focusing and confinement

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We study the focusing of red blood cells and vesicles in pressure-driven flows in highly confined microchannels (10–30 ?m), identifying the control parameters that dictate the cell distribution along the channel. Our results show that an increase in the flow velocity leads to a sharper cell distribution in a lateral position of the channel. This position depends on the channel width, with cells flowing at outer (closer to the walls) positions in thicker channels. We also study the relevance of the object shape, exploring the different behaviour of red blood cells and different vesicles. We also analyze the implications of these phenomena in the cell suspension rheology, highlighting the crucial role of the wall confinement in the rheological properties of the suspension.

### Rheology of red blood cells under flow in higly confined microchannels: I. Effect of elasticity

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We analyze the rheology of dilute red blood cell suspensions in pressure driven flows at low Reynolds number, in terms of the morphologies and elasticity of the cells. We focus on narrow channels of width similar to the cell diameter, when the interactions with the walls dominate the cell dynamics. The suspension presents a shear-thinning behaviour, with a Newtonian-behaviour at low shear rates, an intermediate region of strong decay of the suspension viscosity, and an asymptotic regime at high shear rates in which the effective viscosity converges to that of the solvent. We identify the relevant aspects of cell elasticity that contribute to the rheological response of blood at high confinement. In a second paper, we will explore the focusing of red blood cells while flowing at high shear rates and how this effect is controlled by the geometry of the channel.

### Elastic energies and morphologies of the first stages of the discoechinocyte transition

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Red blood cells are highly sensitive to changes in the relative areas of the two lipid leaflets of the cell membrane. Expansion of the outer leaflet forces the membrane to bend, leading to the deformation of the biconcave discocyte into increasingly spiculated shapes, in a well-defined series of cell shapes known as the discoechinocyte transition. We explore the first stages of this transition by means of an elastic membrane energy model that accounts for the bilayer and cytoskeleton contributions. The morphological evolution is explained in terms of the elastic response of these membrane components. Our results highlight the importance of the cytoskeleton as a stabilizing component and how it determines the strong sequential character of the development of different morphologies. In general, cells develop undulations around the cell contour prior to the growth of out-of-plane bumps; this was found to be due to the high energetic penalty relative to a limited area-difference benefit.