Fluid particle diffusion through high-hematocrit blood flow within a capillary tube

Abstract

Fluid particle diffusion through blood flow within a capillary tube is an important phenomenon to understand, especially for studies in mass transport in the microcirculation as well as in solving technical issues involved in mixing in biomedical microdevices. In this paper, the spreading of tracer particles through up to 20% hematocrit blood, flowing in a capillary tube, was studied using a confocal micro-PTV system. We tracked hundreds of particles in high-hematocrit blood and measured the radial dispersion coefficient. Results yielded significant enhancement of the particle diffusion, due to a micron-scale flow-field generated by red blood cell motions. By increasing the flow rate, the particle dispersion increased almost linearly under constant hematocrit levels. The particle dispersion also showed near linear dependency on hematocrit up to 20%. A scaling analysis of the results, on the assumption that the tracer trajectories were unbiased random walks, was shown to capture the main features of the results. The dispersion of tracer particles was about 0.7 times that of RBCs. These findings provide good insight into transport phenomena in the microcirculation and in biomedical microdevices.

Introduction

Blood is a concentrated suspension of various types of blood cells in plasma, where about 99% of the volume fraction of these different blood cells consists of red blood cells (RBCs). When blood flows in vessels, a micron-scale flow field is generated by RBC motions, which is known to enhance substance diffusion to a level greater than simple Brownian diffusion (Ahuja et al., 1978). Enhancement of mass transport in blood flow is important, because various substances, such as oxygen, nutrients, waste products, and drugs, are transported in the microvascular circulation. The diffusion of platelets is also important, in terms of platelet contact and then adhesion to injured parts of a vascular wall during the first stage of thrombosis formation (Turitto et al., 1972, Wootton and Ku, 1999, Miyazaki and Yamaguchi, 2003). Also, in biomedical microdevices, substances are transported through blood flow within microchannels (Chang et al., 2000, Young and Simmons, 2009). Thus, understanding transport phenomena in microchannels is important not only with regard to physiological and pathological phenomena, but also for designing biomedical microdevices.

To investigate the role of RBCs in the microcirculation transport phenomena, many researchers have studied the motion and dispersion of RBCs in dilute suspensions flowing through glass capillaries (Goldsmith, 1971a, Goldsmith, 1971b, Fischer et al., 1978, Suzuki et al., 1996, Lominadze and Mchedlishvili, 1999, Mchedlishvili and Maeda, 2001, Pries and Secomb, 2003). Because the hematocrit (Hct) in microvessels is around 10–20% (Fung, 1997), it is essential to study blood flow behavior under similar Hct conditions. The main obstacles in tracking RBCs in high-Hct blood are light absorption by hemoglobin and light scattering by RBCs. To overcome this problem, Goldsmith and Turitto (1986) prepared ghost cells by rupturing the RBC membrane and taking out the hemoglobin. Then, they put a small number of RBCs in the suspension of transparent ghost cells and investigated the dispersion of these RBCs. Recently, the authors investigated dispersion of labeled RBCs in concentrated suspensions of healthy RBCs instead of ghost cells (Lima et al., 2008, Lima et al., 2009). Our confocal micro-PTV system enabled the detection of the motions of labeled RBCs even in concentrated suspensions of blood.

While the dispersion of RBCs in blood flow has been investigated widely, there are few reports on the dispersion of fluid particles in blood flow. Goldsmith and coworkers (Goldsmith and Karino, 1977, Goldsmith and Marlow, 1979, Goldsmith and Turitto, 1986) investigated tracer particle dispersion in blood flow, but they also used ghost cells, not RBCs, to visualize particle motions in the concentrated suspension. Recently, Gidaspow and Songprawat (2009) measured the diffusion coefficient of nanoparticles also in a suspension of ghost cells. Although these studies are suggestive and interesting, the use of ghost cells instead of RBCs is an important limitation, because the deformation of RBCs changes markedly by varying the viscosity ratio between the intracellular and extracellular fluids of RBCs. In the case of healthy RBCs in plasma, the viscosity of the intracellular fluid, containing hemoglobin, is about 5–8 times larger than that of plasma. In the case of ghost cells, on the other hand, the intracellular and extracellular fluids are identical and the viscosity ratio is unity. Thus, the dispersion of fluid particles in a concentrated suspension of healthy RBCs needs to be clarified.

In this study, the spreading of tracer particles in concentrated suspensions of healthy RBCs flowing in a capillary tube was investigated. By using a confocal micro-PTV system, we could track particle motions in blood with Hct concentrations of up to 20%. We discuss the effect of Hct, radial position of particles, and flow rate, on tracer particle dispersion. We also demonstrate that a scaling analysis could capture the main features of the results.