Blood Cell Flow Research Articles

Hybrid smoothed dissipative particle dynamics and immersed boundary method for simulation of red blood cells in flows.

In biofluid flow systems, often the flow problems of fluids of complex structures, such as the flow of red blood cells (RBCs) through complex capillary vessels, need to be considered. The smoothed dissipative particle dynamics (SDPD), a particle-based method, is one of the easy and flexible methods to model such complex structure fluids. It couples the best features of the smoothed particle hydrodynamics (SPH) and dissipative particle dynamics (DPD), with parameters having specific physical meaning (coming from SPH discretization of the Navier-Stokes equations), combined with thermal fluctuations in a mesoscale simulation, in a similar manner to the DPD. On the other hand, the immersed boundary method (IBM), a preferred method for handling fluid-structure interaction problems, has also been widely used to handle the fluid-RBC interaction in RBC simulations. In this paper, we aim to couple SDPD and IBM together to carry out the simulations of RBCs in complex flow problems. First, we develop the SDPD-IBM model in details, including the SDPD model for the evolving fluid flow, the RBC model for calculating RBC deformation force, the IBM for treating fluid-RBC interaction, and the solid boundary treatment model as well. We then conduct the verification and validation of the combined SDPD-IBM method. Finally, we demonstrate the capability of the SDPD-IBM method by simulating the flows of RBCs in rectangular, cylinder, curved, bifurcated, and constricted tubes, respectively.

The effect of red blood cells on blood heat transfer

In an attempt to analyze the effect of red blood cells on heat transfer, a two-phase flow heat transfer model of flowing blood was proposed in this paper. In this model, blood is treated as a two-phase fluid composed of red blood cells as the particle phase and plasma as the carrier fluid. The micro-particle dynamics, including aggregation, deformation, mutual collisions of red blood cells and relative movement of red blood cells to plasma, are considered by some equations or simplified methods. The velocity field, temperature field, fluid viscosity and volume fraction of red blood cells in a two-phase blood flow can be calculated using this model. To verify the accuracy of the simulation results of the model, the velocity distribution and heat transfer efficiency calculated by this model were compared with available experimental data from the literature. Good agreement was obtained between these data; thus, this model can accurately simulate the blood flow and heat transfer in a vessel. Then, the model was used to analyze how the micro-particle red blood cells affect the heat transfer of blood, and red blood cells were found to enhance heat transfer efficiency of blood. The viscosity properties of blood, the solid pressure and the lateral movement of red blood cells are the important determinants of this enhancement. The influence of red blood cells on the heat transfer efficiency of pulsatile blood flow was also calculated using this model.

Detection of red blood cell surface antigens by probe-triggered cell collision and flow retardation in an autonomous microfluidic system

Microfluidic devices exploit combined physical, chemical and biological phenomena that could be unique in the sub-millimeter dimensions. The current goal of development of Point-of-Care (POC) medical devices is to extract the biomedical information from the blood. We examined the characteristics of blood flow in autonomous microfluidic devices with the aim to realize sensitive detection of interactions between particulate elements of the blood and the appropriately modified surfaces of the system. As a model experiment we demonstrated the fast analysis of the AB0 blood group system. We observed that the accumulation of red blood cells immobilized on the capillary wall leads to increased lateral movement of the flowing cells, resulting in the overall selective deceleration of the red blood cell flow column compared to the plasma fraction. We showed that by monitoring the flow rate characteristics in capillaries coated with blood type reagents it is possible to identify red blood cell types. Analysis of hydrodynamic effects governing blood flow by Finite Element Method based modelling supported our observations. Our proof-of-concept results point to a novel direction in blood analysis in autonomous microfluidic systems and also provide the basis for the construction of a simple quantitative device for blood group determination.

An on-chip instrument for white blood cells classification based on a lens-less shadow imaging technique

Routine blood tests provide important basic information for disease diagnoses. The proportions of three subtypes of white blood cells (WBCs), which are neutrophils, monocytes, lymphocytes, is key information for disease diagnosis. However, current instruments for routine blood tests, such as blood cell analyzers, flow cytometers, and optical microscopes, are cumbersome, time consuming and expensive. To make a smaller, automatic low-cost blood cell analyzer, much research has focused on a technique called lens-less shadow imaging, which can obtain microscopic images of cells in a lens-less system. Nevertheless, the efficiency of this imaging system is not satisfactory because of two problems: low resolution and imaging diffraction phenomena. In this paper, a novel method of classifying cells with the shadow imaging technique was proposed. It could be used for the classification of the three subtypes of WBCs, and the correlation of the results of classification between the proposed system and the reference system (BC-5180, Mindray) was 0.93. However, the instrument was only 10 × 10 × 10 cm, and the cost was less than $100. Depending on the lens-free shadow imaging technology, the main hardware could be integrated on a chip scale and could be called an on-chip instrument.

Flow Dynamics and HSPC Homing in Bone Marrow Microvessels

SummaryMeasurements of flow velocities at the level of individual arterial vessels and sinusoidal capillaries are crucial for understanding the dynamics of hematopoietic stem and progenitor cell homing in the bone marrow vasculature. We have developed two complementary intravital two-photon imaging approaches to determine blood flow dynamics and velocities in multiple vessel segments by capturing the motion of red blood cells. High-resolution spatiotemporal measurements through a cranial window to determine short-time dynamics of flowing blood cells and repetitive centerline scans were used to obtain a detailed flow-profile map with hemodynamic parameters. In addition, we observed the homing of individual hematopoietic stem and progenitor cells and obtained detailed information on their homing behavior. With our imaging setup, we determined flow patterns at cellular resolution, blood flow velocities and wall shear stress in small arterial vessels and highly branched sinusoidal capillaries, and the cellular dynamics of hematopoietic stem and progenitor cell homing.

Particle tracking for the assessment of microcirculatory perfusion

In recent years the development of portable microscopes, which enable the noninvasive bedside evaluation of the sublingual microcirculation in critically ill patients, has expanded the clinical research on this level of the cardiovascular system. Several semi-quantitative scores have been defined in order to provide researchers with a standardized framework for the offline assessment of the microcirculation status. Among those, space-time diagrams (STDs) constitute an established method for obtaining an estimate of the red blood cells (RBCs) flow velocity in capillaries. However, STDs have the drawback of being time-consuming, inherently subjective, and difficult to manage when the flow is not regular. Objective. In this work we propose an automated method for calculating erythrocyte flow speed, aiming to provide a fast and objective tool for the evaluation of peripheral blood perfusion. Approach. The proposed method exploits an image segmentation module for estimating the positions of candidate flowing cells. A multi-object tracking algorithm based on Kalman filters analyzes and matches the positions corresponding to specific erythrocytes within consecutive frames. Thus, the output of the filter enables to estimate the displacement of each cell, yielding their instantaneous speed. Main results. The method has been validated against the results obtained by the manual analysis of STDs, proving a good agreement for speeds up to 300 μm s−1. At higher speeds, RBC tracking becomes unstable due to the currently limited video acquisition rate (25 Hz) of state-of-the-art devices, that makes the matching between objects appearing in consecutive frames very challenging.

微振動環境下における赤血球流れに関する数値解析

微振動環境下における赤血球流れに関する数値解析

衝突流による赤血球破壊とそれに伴うヘモグロビン漏出の定量

衝突流による赤血球破壊とそれに伴うヘモグロビン漏出の定量

微小管内流れにおける赤血球の断面内分布

微小管内流れにおける赤血球の断面内分布

An Investigation on the Aggregation and Rheodynamics of Human Red Blood Cells Using High Performance Computations.

Studies on the haemodynamics of human circulation are clinically and scientifically important. In order to investigate the effect of deformation and aggregation of red blood cells (RBCs) in blood flow, a computational technique has been developed by coupling the interaction between the fluid and the deformable RBCs. Parallelization was carried out for the coupled code and a high speedup was achieved based on a spatial decomposition. In order to verify the code's capability of simulating RBC deformation and transport, simulations were carried out for a spherical capsule in a microchannel and multiple RBC transport in a Poiseuille flow. RBC transport in a confined tube was also carried out to simulate the peristaltic effects of microvessels. Relatively large-scale simulations were carried out of the motion of 49,512 RBCs in shear flows, which yielded a hematocrit of 45%. The large-scale feature of the simulation has enabled a macroscale verification and investigation of the overall characteristics of RBC aggregations to be carried out. The results are in excellent agreement with experimental studies and, more specifically, both the experimental and simulation results show uniform RBC distributions under high shear rates (60–100/s) whereas large aggregations were observed under a lower shear rate of 10/s.

せん断流れ下における赤血球再配向の数値計算

せん断流れ下における赤血球再配向の数値計算

Statistics for comparison of simulations and experiments of flow of blood cells

In this article we propose statistical method for comparison of simulation and real biological experiments of elastic objects moving in fluid. Our work is focused on future optimization of microfluidic devices used for capture of circulating tumor cells from blood samples. Since the design optimization using biological experiments is both time consuming and expensive, in silico experiments with a broad spectrum of complex and computationally simulations are intensely performed. Necessary verification if simulation models, hitherto mainly realised by comparision of individual cells properties must be extended to more complex simulations. We present our first results with characteristics designed for this purpose.

Numerical simulation of red blood cell flow for investigation of coronary peripheral resistance

Numerical simulation of red blood cell flow for investigation of coronary peripheral resistance

Измерение показателя микроциркуляции крови в капиллярах методом лазерной допплеровской флоуметрии

The paper presents an approach for skin diseases diagnosis with a Laser-Doppler flowmetry evaluation of red blood cells flow changes in capillaries. The target parameter is the dynamic characteristic of blood microcirculation that is the blood flow change per unit time within a volume of interest. The noninvasive diagnostic system “LAKK-M” is utilized for study and comparative analysis of blood microcirculation index, standard deviation of blood flow range and coefficient of variation. Obtained results demonstrate statistical significance of blood microcirculation index measurements for healthy patients and patients suffering from psoriasis and dermatitis. Blood microcirculation index growth is related, firstly, to a vascular tone decrease that leads to increase of blood volume in capillaries. Secondly, index growth can be caused by blood congestion (bradyhemarrhea) that is accompanied by red blood cell concentration increase in the volume of interest due to microcirculation index is directly proportional to red blood cell number. The obtained data should be taken into consideration when developing new approaches for patient data processing and application of a Laser-Doppler flowmetry for early diagnosis of diseases.DOI 10.14258/izvasu(2017)1-02

Intermediate regime and a phase diagram of red blood cell dynamics in a linear flow.

In this paper we investigate the in vitro dynamics of a single rabbit red blood cell (RBC) in a planar linear flow as a function of a shear stress σ and the dynamic viscosity of outer fluid η_{o}. A linear flow is a generalization of previous studies dynamics of soft objects including RBC in shear flow and is realized in the experiment in a microfluidic four-roll mill device. We verify that the RBC stable orientation dynamics is found in the experiment being the in-shear-plane orientation and the RBC dynamics is characterized by observed three RBC dynamical states, namely tumbling (TU), intermediate (INT), and swinging (SW) [or tank-treading (TT)] on a single RBC. The main results of these studies are the following. (i) We completely characterize the RBC dynamical states and reconstruct their phase diagram in the case of the RBC in-shear-plane orientation in a planar linear flow and find it in a good agreement with that obtained in early experiments in a shear flow for human RBCs. (ii) The value of the critical shear stress σ_{c} of the TU-TT(SW) transition surprisingly coincides with that found in early experiments in spite of a significant difference in the degree of RBC shape deformations in both the SW and INT states. (iii) We describe the INT regime, which is stationary, characterized by strong RBC shape deformations and observed in a wide range of the shear stresses. We argue that our observations cast doubts on the main claim of the recent numerical simulations that the only RBC spheroidal stress-free shape is capable to explain the early experimental data. Finally, we suggest that the amplitude dependence of both θ and the shape deformation parameter D on σ can be used as the quantitative criterion to determine the RBC stress-free shape.

Abstract 11383: Reversal of Post-stroke Cerebral Microvascular Dysfunction by Neuroprotective and Hyperdynamic Therapy for Experimental Subarachnoid Hemorrhage

Introduction: Early brain injury characterized by microvascular dysfunction in cerebral vessels may play an important role in the development of delayed cerebral ischemia (DCI) or vasospasm after subarachnoid hemorrhage (SAH). However, little is known as to the microcirculatory mechanism(s) to treat post-SAH DCI. Hypothesis: To clarify the utility of neuroprotective and hyperdynamic therapy in relieving cerebral microcirculatory dysfunction affected by vasospasm after experimental SAH. Methods: Male C57BL/6 mice were subjected to SAH by endovascular perforation and minocycline for antibiotic and anti-inflammatory use was started. Closed cranial bone window was then made over the left somatosensory cortex. In vivo real-time imaging was performed using 2-photon laser-scanning microscopy at postoperative day 3 to record alterations on the level of cerebral microvessels and the effects of dobutamine hyperdynamic therapy at clinical dose were evaluated. Comparison was made with a group without minocycline administration. Results: According to the 3-dimentional observation, >50% of pial and penetrating arteries constricted moderately (25-50%) from day 2 to 3 after SAH, which was greater in number in a group without minocycline pretreatment (p>0.05). In areas close to the microvasospasm, blood cell flow as measured by line scan increased by 24% (range, from 7 to 39%) following dobutamine infusion. Reversal of flow stagnation by dobutamine was more prominently observed in animals with minocycline pretreatment in pial and penetrating arteries (1.2 ± 0.5 vs. 1.8 ± 1.0 mm/s, p<0.05). Diameters of the microvessels or location of microthrombi in precapillary arterioles were not affected in any of the groups (p>0.05). Conclusions: The data suggest that early neuroprotection followed by inotropic hemodynamic therapy can improve microcirculation in specific areas affected by microvasospasm, which may in part, explain novel therapeutic targets for the early treatment of DCI after SAH.

Analytical solution of the correlation transport equation with static background: beyond diffuse correlation spectroscopy.

The correlation transport equation (CTE) is the natural generalization of the theory for diffusion correlation spectroscopy and represents a more precise model when dealing with measurements of particle movement in fluids or red blood cell flow in biological tissues. Unfortunately, the CTE is not methodically used due to the complexity of finding solutions. It is shown that actually a very simple modification of the theory/software for the solution of the radiative transport equation allows one to obtain exact solutions of the CTE. The presence of a static background is also taken into account and its influence on the CTE solutions is discussed. The proposed approach permits one to easily work beyond the diffusion regime and potentially for any optical and/or physiological value. The validity of the approach is demonstrated by using "gold standard" Monte Carlo simulations.

Label-free analysis of mononuclear human blood cells in microfluidic flow by coherent imaging tools.

The investigation of the physical properties of peripheral blood mononuclear cells (PBMC) is of great relevance, as they play a key role in regulating human body health. Here we report the possibility to characterize human PBMC in their physiological conditions in a microfluidic-based measurement system. A viscoelastic polymer solution is adopted for 3D alignment of individual cells inflow. An optical signature (OS) acquisition of each flowing cell is performed using a wide angle light scattering apparatus. Besides, a quantitative phase imaging (QPI) holographic system is employed with the aim (i) to check the position in flow of individual cells using a holographic 3D cell tracking method; and (ii) to estimate their 3D morphometric features, such as their refractive index (RI). Results obtained by combining OS and QPI have been compared with literature values, showing good agreement. The results confirm the possibility to obtain sub-micrometric details of physical cell properties in microfluidic flow, avoiding chemical staining or fluorescent labelling.

Numerical Investigation of the Influence of the Flow Channel Gap on Performances of Axial Flow Maglev Blood Pump

Artificial heart pump (referred to as blood pump) has become an essential means to save patients with heart failure. The pump head, the flow shear stress, blood cell flow path have a close relationship with hemodynamic characteristics. And the flow channel gap is one of the main structural parameters of the blood pump that affects the flow characteristics. For an axial flow maglev blood pump, based on CFD, using k-ε model, unstructured mesh, establishing the whole flow channel model, a three-dimensional numerical simulation of axial flow maglev blood pump was carried. The relationship between the port clearance ratio and the pump head, the flow shear stress, blood cell flow path was explored. Simulation results show that: the port clearance ratio δ=0.75, the flow channel gap h = 2.5mm, blade height b = 1.8mm, the optimal performance was attained. The pump head reached 120mmHg, the maximum shear force was less than 450Pa, both meet the functional requirements and reduce the blood damage. This results provide an important basis for structure design of axial flow maglev blood pump.

Flow of Red Blood Cells in Stenosed Microvessels.

A computational study is presented on the flow of deformable red blood cells in stenosed microvessels. It is observed that the Fahraeus-Lindqvist effect is significantly enhanced due to the presence of a stenosis. The apparent viscosity of blood is observed to increase by several folds when compared to non-stenosed vessels. An asymmetric distribution of the red blood cells, caused by geometric focusing in stenosed vessels, is observed to play a major role in the enhancement. The asymmetry in cell distribution also results in an asymmetry in average velocity and wall shear stress along the length of the stenosis. The discrete motion of the cells causes large time-dependent fluctuations in flow properties. The root-mean-square of flow rate fluctuations could be an order of magnitude higher than that in non-stenosed vessels. Several folds increase in Eulerian velocity fluctuation is also observed in the vicinity of the stenosis. Surprisingly, a transient flow reversal is observed upstream a stenosis but not downstream. The asymmetry and fluctuations in flow quantities and the flow reversal would not occur in absence of the cells. It is concluded that the flow physics and its physiological consequences are significantly different in micro- versus macrovascular stenosis.