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

Correction for ‘Cross-sectional focusing of red blood cells in a constricted microfluidic channel’ by Asena Abay et al., Soft Matter, 2020, 16, 534–543

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.Comment: accepted for soft matte

"So is science …"1 : No evidence for neocytolysis on descending the mountains (Response to Rice and Gunga).

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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

Heterogeneous flow inside threads of low viscosity fluids leads to anomalous long filament lifetimes

Formation and breakup of fluid threads is pervasive in nature and technology, where high extensibility of fluid filaments and extended filament lifetimes are commonly observed as a consequence of fluid viscoelasticity. In contrast, threads of low viscous Newtonian fluids like water rupture quickly. Here, we demonstrate that a unique banding instability during filament thinning of model surfactant solutions, with a viscosity close to water and no measurable elasticity, leads to extremely long filament lifetimes and to the formation of remarkably long threads. Complementary measurements in planar extension as well as in shear reveal that this flow instability is characterized by a multivalued stress, arising beyond a critical strain rate, irrespective of flow kinematics. Our work reports the first observation of such phenomena during extensional deformation and provides a unifying view on instabilities in complex flow fields

Effect of Cell Age and Membrane Rigidity on Red Blood Cell Shape in Capillary Flow

Blood flow in the microcirculatory system is crucially affected by intrinsic red blood cell (RBC) properties, such as their deformability. In the smallest vessels of this network, RBCs adapt their shapes to the flow conditions. Although it is known that the age of RBCs modifies their physical properties, such as increased cytosol viscosity and altered viscoelastic membrane properties, the evolution of their shape-adapting abilities during senescence remains unclear. In this study, we investigated the effect of RBC properties on the microcapillary in vitro flow behavior and their characteristic shapes in microfluidic channels. For this, we fractioned RBCs from healthy donors according to their age. Moreover, the membranes of fresh RBCs were chemically rigidified using diamide to study the effect of isolated graded-membrane rigidity. Our results show that a fraction of stable, asymmetric, off-centered slipper-like cells at high velocities decreases with increasing age or diamide concentration. However, while old cells form an enhanced number of stable symmetric croissants at the channel centerline, this shape class is suppressed for purely rigidified cells with diamide. Our study provides further knowledge about the distinct effects of age-related changes of intrinsic cell properties on the single-cell flow behavior of RBCs in confined flows due to inter-cellular age-related cell heterogeneity

Cross-talk between red blood cells and plasma influences blood flow and omics phenotypes in severe COVID-19

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

Erysense, a Lab-on-a-Chip-Based Point-of-Care Device to Evaluate Red Blood Cell Flow Properties With Multiple Clinical Applications

In many medical disciplines, red blood cells are discovered to be biomarkers since they “experience” various conditions in basically all organs of the body. Classical examples are diabetes and hypercholesterolemia. However, recently the red blood cell distribution width (RDW), is often referred to, as an unspecific parameter/marker (e.g., for cardiac events or in oncological studies). The measurement of RDW requires venous blood samples to perform the complete blood cell count (CBC). Here, we introduce Erysense, a lab-on-a-chip-based point-of-care device, to evaluate red blood cell flow properties. The capillary chip technology in combination with algorithms based on artificial neural networks allows the detection of very subtle changes in the red blood cell morphology. This flow-based method closely resembles in vivo conditions and blood sample volumes in the sub-microliter range are sufficient. We provide clinical examples for potential applications of Erysense as a diagnostic tool [here: neuroacanthocytosis syndromes (NAS)] and as cellular quality control for red blood cells [here: hemodiafiltration (HDF) and erythrocyte concentrate (EC) storage]. Due to the wide range of the applicable flow velocities (0.1–10 mm/s) different mechanical properties of the red blood cells can be addressed with Erysense providing the opportunity for differential diagnosis/judgments. Due to these versatile properties, we anticipate the value of Erysense for further diagnostic, prognostic, and theragnostic applications including but not limited to diabetes, iron deficiency, COVID-19, rheumatism, various red blood cell disorders and anemia, as well as inflammation-based diseases including sepsis

Cross-talk between red blood cells and plasma influences blood flow and omics phenotypes in severe COVID-19

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