arXiv subjects

Thomas John

Publications and source records attributed to Thomas John.

16 recordsLinked to original sources

arXiv2024

Competing aggregation and iso-density equilibrium lead to band pattern formation in density gradients

Centrifugation of biological matter in density gradient solutions is a standard method for separating cell types or components. It is also used to separate red blood cells (RBCs) by age, as they lose water and become denser over their lifespan. When the density gradient is prepared with Percoll, discrete bands of RBCs are systematically observed along the gradient, despite the continuous density distribution of RBCs. Early studies suggested that cell aggregation might influence spatial distribution, but it remains debated whether a continuous density population can form discrete bands. We developed a continuity equation incorporating cell aggregation to describe the macroscopic evolution of RBC volume fraction in a density gradient, considering a continuous RBC density distribution. Numerical solutions demonstrate that the competition between isodensity distribution and aggregation is sufficient to create band patterns. Our model reproduces the temporal evolution observed in experiments, but also predicts several types of bifurcation-like behaviors for the steady-state patterns in constant gradients, depending on RBC volume fraction and aggregation energy. This demonstrates that the competition between RBC aggregation and iso-density distribution is a novel mechanism driving pattern formation.

cond-mat.soft↗

arXiv2024

Deposit of Red Blood Cells at low concentrations in evaporating droplets: central edge growth and potential applications

Evaporation of blood droplets and diluted blood samples is a topic of intensive research, as it is seen as a possible low-cost tool for diagnosis. So far, samples with volume fraction down to a few percents of Red Blood Cells (RBCs) have been studied, and those were reportedly dominated by a ``coffee-ring'' deposit. In this study, samples with lower volume fractions have been used in order to study the growth of the evaporative deposit from sessile droplets more in details. We observed that blood samples and salt solutions with less than 1\% volume fraction of RBCs are dominated by a central deposit. We characterized the growth process of this central deposit by evaporating elongated drops, and determined that it is consistent with the Kardar-Parisi-Zhang process in the presence of quenched disorder. Our results showed a sensitivity of this deposit size to the fibrinogen concentration and shape of the RBCs, meaning that this parameter could be used to develop a new and cost-effective clinical marker for inflammation and RBC deformation.

cond-mat.soft↗

arXiv2023

Early stage of Erythrocyte Sedimentation Rate test: Fracture of a high-volume-fraction gel

Erythrocyte Sedimentation Rate (ESR) is a clinical parameter used as a non-specific marker for inflammation, and recent studies have shown that it is linked to the collapse of the gel formed by red blood cells (RBCs) at physiological hematocrits (i.e. RBC volume fraction). Previous research has suggested that the delay time before the sedimentation process is related to the formation of fractures in the gel. Moreover, RBC gels present specific properties due to the anisotropic shape and flexibility of the RBCs. Namely, the onset of the collapse is reached earlier and the settling velocity of the gel increases with increasing attraction between the RBCs, while gel of spherical particles show the opposite trend. Here, we report experimental observations of the gel structure during this onset and suggest an equation modeling this initial process as fracturing of the gel. We demonstrate that this equation provides a model for the motion of the interface between blood plasma and the RBC gel, along the whole time span. We also observe that the increase in the attraction between the RBCs modifies the density of fractures in the gel, which explains why the gel displays a decrease in delay time when the aggregation energy between the RBCs increases. Our work uncovers the detailed physical mechanism underlying the ESR and provides insights into the fracture dynamics of a RBC gel. These results can improve the accuracy of clinical measurements.

cond-mat.soft↗

arXiv2023

Cell-free layer development and spatial organization of healthy and rigid red blood cells in a microfluidic bifurcation

Bifurcations and branches in the microcirculation dramatically affect blood flow as they determine the spatiotemporal organization of red blood cells (RBCs). Such changes in vessel geometries can further influence the formation of a cell-free layer (CFL) close to the vessel walls. Biophysical cell properties, such as their deformability, which is impaired in various diseases, are often thought to impact blood flow and affect the distribution of flowing RBCs. This study investigates the flow behavior of healthy and artificially hardened RBCs in a bifurcating microfluidic T-junction. We determine the RBC distribution across the channel width at multiple positions before and after the bifurcation. Thus, we reveal distinct focusing profiles in the feeding mother channel for rigid and healthy RBCs that dramatically impact the cell organization in the successive daughter channels. Moreover, we experimentally show how the characteristic asymmetric CFLs in the daughter vessels develop along their flow direction. Complimentary numerical simulations indicate that the buildup of the CFL is faster for healthy than for rigid RBCs. Our results provide fundamental knowledge to understand the partitioning of rigid RBC as a model of cells with pathologically impaired deformability in complex in vitro networks.

physics.bio-ph↗

arXiv2023

Cell-free layer of red blood cells in a constricted microfluidic channel under steady and time-dependent flow conditions

Constricted blood vessels in the circulatory system can severely impact the spatiotemporal organization of red blood cells (RBCs) causing various physiological complications. In lab-on-a-chip applications, constrictions are commonly used for cell sorting and plasma separation based on the formation of a cell-free layer (CFL) at the channel boundary. However, such devices usually employ a steady flow, although time-dependent and pulsatile flow conditions enhance many microfluidic operations and possess significant relevance for in-vitro studies under physiologically relevant flow conditions. In this study, we examine the CFL dynamics in a constricted microchannel under steady and time-dependent flow. Therefore, we develop an image processing routine that allows us to resolve the spatiotemporal evolution of the CFL under time-dependent driving of the flow with arbitrary waveform. First, we perform a characterization of the CFL and the cell-free area (CFA) before and after the constriction under steady flow conditions. Second, we employ our method to study the effect of the hematocrit and the parameters of the flow modulations on the CFL and CFA using a sinusoidal pressure profile. Our results highlight the dominant effects of the RBC concentration and the amplitude of the applied pressure signal predominantly on the CFA dynamics. Moreover, we observe a dampening of the CFA amplitude with increasing hematocrit or decreasing pressure amplitude, and a peculiar phase shift of the CFA oscillations pre- and post-constriction. Complementary numerical simulations reveal how the time-dependent CFA dynamics are coupled with the dynamically changing flow field at the constriction. Due to the increasing demand for investigations and applications under time-dependent flow conditions, our study provides crucial insight into the flow behavior of complex fluids in unsteady microscale flows.

physics.flu-dyn↗

arXiv2021

Red blood cell shape transitions and dynamics in time-dependent capillary flows

The dynamics of single red blood cells (RBCs) determine microvascular blood flow by adapting their shape to the flow conditions in the narrow vessels. In this study, we explore the dynamics and shape transitions of RBCs on the cellular scale under confined and unsteady flow conditions using a combination of microfluidic experiments and numerical simulations. Tracking RBCs in a comoving frame in time-dependent flows reveals that the mean transition time from the symmetric croissant to the off-centered, non-symmetric slipper shape is significantly faster than the opposite shape transition, which exhibits pronounced cell rotations. Complementary simulations indicate that these dynamics depend on the orientation of the RBC membrane in the channel during the time-dependent flow. Moreover, we show how the tank-treading movement of slipper-shaped RBCs in combination with the narrow channel leads to oscillations of the cell's center of mass. The frequency of these oscillations depends on the cell velocity, the viscosity of the surrounding fluid, and the cytosol viscosity. These results provide a potential framework to identify and study pathological changes of RBC properties.

physics.bio-ph↗

arXiv2021

Erythrocyte sedimentation: Effect of aggregation energy on gel structure during collapse

The erythrocyte (or red blood cell) sedimentation rate (ESR) is commonly interpreted as a measure of cell aggregation and as a biomarker of inflammation. It is well known that an increase of fibrinogen concentration, an aggregation-inducing protein for erythrocytes, leads to an increase of the sedimentation rate of erythrocytes, which is generally explained through the formation and faster settling of large disjoint aggregates. However, many aspects of erythrocyte sedimentation conform well with the collapse of a colloidal gel rather than with the sedimentation of disjoint aggregates. Using experiments and cell-level numerical simulations, we systematically investigate the dependence of ESR on fibrinogen concentration and its relation to the microstructure of the gel-like erythrocyte suspension. We show that for physiological aggregation interactions, an increase in the attraction strength between cells results in a cell network with larger void spaces. This geometrical change in the network structure occurs due to anisotropic shape and deformability of erythrocytes and leads to an increased gel permeability and faster sedimentation. Our results provide a comprehensive relation between the ESR and the cell-level structure of erythrocyte suspensions and support the gel hypothesis in the interpretation of blood sedimentation.

cond-mat.soft↗

arXiv2021

Erythrocyte sedimentation: Fracture and collapse of a high-volume-fraction soft-colloid gel

The erythrocyte sedimentation rate is one of the oldest medical diagnostic methods whose physical mechanisms remain debatable up to date. Using both light microscopy and mesoscale cell-level simulations, we show that erythrocytes form a soft-colloid gel. Furthermore, the high volume fraction of erythrocytes, their deformability, and weak attraction lead to unusual properties of this gel. A theoretical model for the gravitational collapse is developed, whose predictions are in agreement with detailed macroscopic measurements of the interface velocity.

cond-mat.soft↗

arXiv2021

Vortical flow structures induced by red blood cells in capillaries

Knowledge about the flow field of the plasma around the red blood cells in capillary flow is important for a physical understanding of blood flow and the transport of micro- and nanoparticles and molecules in the flowing plasma. We conduct an experimental study on the flow field around red blood cells in capillary flow that are complemented by simulations of vortical flow between red blood cells. Red blood cells were injected in a 10x12 micrometer rectangular microchannel at a low hematocrit and the flow field around a single or two cells have been characterized thanks to a highspeed camera and by tracking 250 nm nanoparticles in flow behaving as tracers. While the flow field around a steady croissant shape is found to be relatively similar to that of a rigid sphere, the flow field around a slipper shape exhibits a small vortex at the rear of the red blood cell. Even more pronounced are vortex-like structures observed in the central region between two neighboring croissants. Conclusions: The rotation frequency of the vortices is to a good approximation, inversely proportional to the distance between the cells. Our experimental data are confirmed and complemented by numerical simulations.

physics.bio-ph↗

arXiv2019

Cross-sectional focusing of red blood cells in a constricted microfluidic channel

Constrictions in blood vessels and microfluidic devices can dramatically change the spatial distribution of passing cells or particles and are commonly used in biomedical cell sorting applications. However, the three-dimensional nature of cell focusing in the channel cross-section remains poorly investigated. Here, we explore the cross-sectional distribution of living and rigid red blood cells passing a constricted microfluidic channel by tracking individual cells in multiple layers across the channel depth and across the channel width. While cells are homogeneously distributed in the channel cross-section pre-contraction, we observe a strong geometry-induced focusing towards the four channel faces post-contraction. The magnitude of this cross-sectional focusing effect increases with increasing Reynolds number for both living and rigid red blood cells. We discuss how this non-uniform cell distribution downstream of the contraction results in an apparent double-peaked velocity profile in particle image velocimetry analysis and show that trapping of red blood cells in the recirculation zones of the abrupt construction depends on cell deformability.

physics.flu-dyn↗

arXiv2019

Flagellar number governs bacterial spreading and transport efficiency

Peritrichous bacteria synchronize and bundle their flagella to actively swim while disruption of the bundle leads to tumbling. It is still not known whether the number of flagella represents an evolutionary adaptation towards optimizing bacterial navigation. Here, we study the swimming dynamics of differentially flagellated Bacillus subtilis strains in a quasi-two-dimensional system. We find that decreasing the number of flagella N reduces the average turning angle between two successive run phases and enhances the duration and directional persistence of the run phase. As a result, having less flagella is beneficial for long-distance transport and fast spreading, while having a lot of flagella is advantageous for the processes which require localization and slow dynamics, such as biofilm formation. We develop a two-state random walk model that incorporates spontaneous switchings between the states and yields exact analytical expressions for transport properties, in remarkable agreement with experiments. The results of numerical simulations based on our two-state model suggest that the efficiency of searching and exploring the environment is optimized at intermediate values of N. The optimal choice of N, for which the search time is minimized, decreases with increasing the size of the environment in which the bacteria swim.

physics.bio-ph↗

arXiv2018

Vesicle dynamics in confined steady and harmonically modulated Poiseuille flows

We present a numerical study of the time-dependent motion of a two-dimensional vesicle in a channel under an imposed flow. In a Poiseuille flow the shape of the vesicle depends on the flow strength, the mechanical properties of the membrane, and the width of the channel as reported in the past. This study is focused on the centered snaking (CSn) shape, where the vesicle shows an oscillatory motion like a swimmer flagella even though the flow is stationary. We quantify this behavior by the amplitude and frequency of the oscillations of the vesicle's center of mass. We observe regions in parameter space, where the CSn coexists with the parachute or the unconfined slipper. The influence of an amplitude modulation of the imposed flow on the dynamics and shape of the snaking vesicle is also investigated. For large modulation amplitudes transitions to static shapes are observed. A smaller modulation amplitude induces a modulation in amplitude and frequency of the center of mass of the snaking vesicle. In a certain parameter range we find that the center of mass oscillates with a constant envelope indicating the presence of at least two stable states.

physics.bio-ph↗

arXiv2017

Numerical-experimental observation of shape bistability of red blood cells flowing in a microchannel

Red blood cells flowing through capillaries assume a wide variety of different shapes owing to their high deformability. Predicting the realized shapes is a complex field as they are determined by the intricate interplay between the flow conditions and the membrane mechanics. In this work we construct the shape phase diagram of a single red blood cell with a physiological viscosity ratio flowing in a microchannel. We use both experimental in-vitro measurements as well as 3D numerical simulations to complement the respective other one. Numerically, we have easy control over the initial starting configuration and natural access to the full 3D shape. With this information we obtain the phase diagram as a function of initial position, starting shape and cell velocity. Experimentally, we measure the occurrence frequency of the different shapes as a function of the cell velocity to construct the experimental diagram which is in good agreement with the numerical observations. Two different major shapes are found, namely croissants and slippers. Notably, both shapes show coexistence at low (<1 mm/s) and high velocities (>3 mm/s) while in-between only croissants are stable. This pronounced bistability indicates that RBC shapes are not only determined by system parameters such as flow velocity or channel size, but also strongly depend on the initial conditions.

physics.bio-ph↗

arXiv2016

Cluster of red blood cells in microcapillary flow: hydrodynamic versus macromolecule induced interaction

We present experiments on RBCs that flow through microcapillaries under physiological conditions. We show that the RBC clusters form as a subtle imbrication between hydrodynamics interaction and adhesion forces because of plasma proteins. Clusters form along the capillaries and macromolecule-induced adhesion contribute to their stability. However, at high yet physiological flow velocities, shear stresses overcome part of the adhesion forces, and cluster stabilization due to hydrodynamics becomes stronger. For the case of pure hydrodynamic interaction, cell-to-cell distances have a pronounced bimodal distribution. Our 2D-numerical simulations on vesicles captures the transition between adhesive and non-adhesive clusters at different flow velocities.

physics.bio-ph↗

arXiv2006

Influence of surface tension on the conical miniscus of a magnetic fluid in the field of a current-carrying wire

We study the influence of surface tension on the shape of the conical miniscus built up by a magnetic fluid surrounding a current-carrying wire. Minimization of the total energy of the system leads to a singular second order boundary value problem for the function $ζ(r)$ describing the axially symmetric shape of the free surface. An appropriate transformation regularizes the problem and allows a straightforward numerical solution. We also study the effects a superimposed second liquid, a nonlinear magnetization law of the magnetic fluid, and the influence of the diameter of the wire on the free surface profile.

cond-mat.mtrl-sci↗

arXiv1999

On-off Intermittency in Stochastically Driven Electrohydrodynamic Convection in Nematics

We report on-off intermittency in electroconvection of nematic liquid crystals driven by a dichotomous stochastic electric voltage. With increasing voltage amplitude we observe laminar phases of undistorted director state interrupted by shorter bursts of spatially regular stripes. Near a critical value of the amplitude the distribution of the duration of laminar phases is governed over several decades by a power law with exponent -3/2. The experimental findings agree with simulations of the linearized electrohydrodynamic equations near the sample stability threshold.

patt-sol↗