Asymmetry of red blood cell motions in a microchannel with a diverging and converging bifurcation.
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ABSTRACT:
SUBMITTER: Leble V
PROVIDER: S-EPMC3368833 | biostudies-other | 2011 Dec
REPOSITORIES: biostudies-other
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Project description:The loss of the red blood cells (RBCs) deformability is related with many human diseases, such as malaria, hereditary spherocytosis, sickle cell disease, or renal diseases. Hence, during the last years, a variety of technologies have been proposed to gain insights into the factors affecting the RBCs deformability and their possible direct association with several blood pathologies. In this work, we present a simple microfluidic tool that provides the assessment of motions and deformations of RBCs of end-stage kidney disease (ESKD) patients, under a well-controlled microenvironment. All of the flow studies were performed within a hyperbolic converging microchannels where single-cell deformability was assessed under a controlled homogeneous extensional flow field. By using a passive microfluidic device, RBCs passing through a hyperbolic-shaped contraction were measured by a high-speed video microscopy system, and the velocities and deformability ratios (DR) calculated. Blood samples from 27 individuals, including seven healthy controls and 20 having ESKD with or without diabetes, were analysed. The obtained data indicates that the proposed device is able to detect changes in DR of the RBCs, allowing for distinguishing the samples from the healthy controls and the patients. Overall, the deformability of ESKD patients with and without diabetes type II is lower in comparison with the RBCs from the healthy controls, with this difference being more evident for the group of ESKD patients with diabetes. RBCs from ESKD patients without diabetes elongate on average 8% less, within the hyperbolic contraction, as compared to healthy controls; whereas, RBCs from ESKD patients with diabetes elongate on average 14% less than the healthy controls. The proposed strategy can be easily transformed into a simple and inexpensive diagnostic microfluidic system to assess blood cells deformability due to the huge progress in image processing and high-speed microvisualization technology.
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Project description:The deformability of a red blood cell (RBC) is one of the most important biological parameters affecting blood flow, both in large arteries and in the microcirculation, and hence it can be used to quantify the cell state. Despite numerous studies on the mechanical properties of RBCs, including cell rigidity, much is still unknown about the relationship between deformability and the configuration of flowing cells, especially in a confined rectangular channel. Recent computer simulation techniques have successfully been used to investigate the detailed behavior of RBCs in a channel, but the dynamics of a translating RBC in a narrow rectangular microchannel have not yet been fully understood. In this study, we numerically investigated the behavior of RBCs flowing at different velocities in a narrow rectangular microchannel that mimicked a microfluidic device. The problem is characterized by the capillary number C a , which is the ratio between the fluid viscous force and the membrane elastic force. We found that confined RBCs in a narrow rectangular microchannel maintained a nearly unchanged biconcave shape at low C a , then assumed an asymmetrical slipper shape at moderate C a , and finally attained a symmetrical parachute shape at high C a . Once a RBC deformed into one of these shapes, it was maintained as the final stable configurations. Since the slipper shape was only found at moderate C a , measuring configurations of flowing cells will be helpful to quantify the cell state.
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Project description:OBJECTIVE:To advance the goal of "Grand Convergence" in global health by 2035, this study tested the convergence hypothesis in the progress of the health status of individuals from 193 countries, using both standard and cutting-edge convergence metrics. METHODS:The study used multiple data sources. The methods section is categorized into two parts. (1) Health inequality measures were used for estimating inter-country inequalities. Dispersion Measure of Mortality (DMM) is used for measuring absolute inequality and Gini Coefficient for relative inequality. (2) We tested the standard convergence hypothesis for the progress in Infant Mortality Rate (IMR) and Life Expectancy at Birth (LEB) during 1950 to 2015 using methods ranging from simple graphical tools (catching-up plots) to standard parametric (absolute β and σ-convergence) and nonparametric econometric models (kernel density estimates) to detect the presence of convergence (or divergence) and convergence clubs. FINDINGS:The findings lend support to the "rise and fall" of world health inequalities measured using Life Expectancy at Birth (LEB) and Infant Mortality Rate (IMR). The test of absolute β-convergence for the entire period and in the recent period supports the convergence hypothesis for LEB (β = -0.0210 [95% CI -0.0227 - -0.0194], p<0.000) and rejects it for IMR (β = 0.0063 [95% CI 0.0037-0.0089], p<0.000). However, results also suggest a setback in the speed of convergence in health status across the countries in recent times, 5.4% during 1950-55 to 1980-85 compared to 3% during 1985-90 to 2010-15. Although inequality based convergence metrics showed evidence of divergence replacing convergence during 1985-90 to 2000-05, from the late 2000s, divergence was replaced by re-convergence although with a slower speed of convergence. While the non-parametric test of convergence shows an emerging process of regional convergence rather than global convergence. CONCLUSION:We found that with a current rate of progress (2.2% per annum) the "Grand convergence" in global health can be achieved only by 2060 instead of 2035. We suggest that a roadmap to achieve "Grand Convergence" in global health should include more radical changes and work for increasing efficiency with equity to achieve a "Grand convergence" in health status across the countries by 2035.
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Project description:It is well known that certain pathological conditions result in a decrease of red blood cells (RBCs) deformability and subsequently can significantly alter the blood flow in microcirculation, which may block capillaries and cause ischemia in the tissues. Microfluidic systems able to obtain reliable quantitative measurements of RBC deformability hold the key to understand and diagnose RBC related diseases. In this work, a microfluidic system composed of a microchannel with a hyperbolic-shaped contraction followed by a sudden expansion is presented. We provide a detailed quantitative description of the degree of deformation of human RBCs under a controlled homogeneous extensional flow field. We measured the deformation index (DI) as well as the velocity of the RBCs travelling along the centerline of the channel for four different flow rates and analyze the impact of the particle Reynolds number. The results show that human RBC deformation tends to reach a plateau value in the region of constant extensional rate, the value of which depends on the extension rate. Additionally, we observe that the presence of a sudden expansion downstream of the hyperbolic contraction modifies the spatial distribution of cells and substantially increases the cell free layer (CFL) downstream of the expansion plane similarly to what is seen in other expansion flows. Beyond a certain value of flow rate, there is only a weak effect of inlet flow rates on the enhancement of the downstream CFL. These in vitro experiments show the potential of using microfluidic systems with hyperbolic-shaped microchannels both for the separation of the RBCs from plasma and to assess changes in RBC deformability in physiological and pathological situations for clinical purposes. However, the selection of the geometry and the identification of the most suitable region to evaluate the changes on the RBC deformability under extensional flows are crucial if microfluidics is to be used as an in vitro clinical methodology to detect circulatory diseases.
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Project description:Red blood cell (RBC) aggregation is a multifaceted phenomenon, and whether it is generally beneficial or deleterious remains unclear. In order to better understand its effect on microvascular blood flow, the phenomenon must be studied in complex geometries, as it is strongly dependent on time, flow, and geometry. The cell-depleted layer (CDL) which forms at the walls of microvessels has been observed to be enhanced by aggregation; however, details of the characteristics of the CDL in complex regions, such as bifurcations, require further investigation. In the present study, a microchannel with a T-junction was used to analyze the influence of aggregation on the flow field and the CDL. Micro-PIV using RBCs as tracers provided high resolution cell velocity data. CDL characteristics were measured from the same data using a newly developed technique based on motion detection. Skewed and sharpened velocity profiles in the daughter branches were observed, contrary to the behavior of a continuous Newtonian fluid. RBC aggregation was observed to increase the skewness, but decrease the sharpening, of the velocity profiles in the daughter branches. The CDL width was found to be significantly greater, with a wider distribution, in the presence of aggregation and the mean width increased proportionally with the reciprocal of the fraction of flow entering the daughter branch. Aggregation also significantly increased the roughness of the interface between the CDL and the RBC core. The present results provide further insight into how RBC aggregation may affect the flow in complex geometries, which is of importance in both understanding its functions invivo, and utilizing it as a tool in microfluidic devices.
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Project description:The non-uniform partitioning or phase separation of red blood cells (RBCs) at a diverging bifurcation of a microvascular network is responsible for RBC heterogeneity within the network. The mechanisms controlling RBC heterogeneity are not yet fully understood and there is a need to improve the basic understanding of the phase separation phenomenon. In this context, in vitro experiments can fill the gap between existing in vivo and in silico models as they provide better controllability than in vivo experiments without mathematical idealizations or simplifications inherent to in silico models. In this study, we fabricated simple models of symmetric/asymmetric microvascular networks; we provided quantitative data on the RBC velocity, line density and flux in the daughter branches. In general our results confirmed the tendency of RBCs to enter the daughter branch with higher flow rate (Zweifach-Fung effect); in some cases even inversion of the Zweifach-Fung effect was observed. We showed for the first time a reduction of the Zweifach-Fung effect with increasing flow rate. Moreover capillary dilation was shown to cause an increase of RBC line density and RBC residence time within the dilated capillary underlining the possible role of pericytes in regulating the oxygen supply.
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Project description:Understanding the elongational rheology of dilute polymer solutions plays an important role in many biological and industrial applications ranging from microfluidic lab-on-a-chip diagnostics to phenomena such as fuel atomization and combustion. Making quantitative measurements of the extensional viscosity for dilute viscoelastic fluids is a long-standing challenge and it motivates developments in microfluidic fabrication techniques and high speed/strobe imaging of millifluidic capillary phenomena in order to develop new classes of instruments. In this paper, we study the elongational rheology of a family of dilute polymeric solutions in two devices: first, steady pressure-driven flow through a hyperbolic microfluidic contraction/expansion and, second, the capillary driven breakup of a thin filament formed from a small diameter jet ([Formula: see text]). The small length scale of the device allows very large deformation rates to be achieved. Our results show that in certain limits of low viscosity and elasticity, jet breakup studies offer significant advantages over the hyperbolic channel measurements despite the more complex implementation. Using our results, together with scaling estimates of the competing viscous, elastic, inertial and capillary timescales that control the dynamics, we construct a dimensionless map or nomogram summarizing the operating space for each instrument.
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