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Due to recent advances in micro total analysis system technologies, microfluidics provides increased opportunities to manipulate, stimulate, and diagnose blood cells. Controlling the concentration of cells at a given position across the width of a channel is an important aspect in the design of microfluidic devices. Despite its biomedical importance, the collective spreading of red blood cells (RBCs) in a microchannel has not yet been fully clarified. In this study, we experimentally investigated the collective spreading of RBCs in a straight microchannel, and found that RBCs initially distributed in one side of the microchannel spread to the spanwise direction during downstream flow. Spreading increased considerably as the hematocrit increased, though the flow rate had a small effect. We proposed a scaling argument to show that this spreading phenomenon was diffusive and mainly induced by cell–cell interactions. The dispersion coefficient was approximately proportional to the flow rate and the hematocrit. These results are useful in understanding collective behaviors of RBCs in a microchannel and in microcirculation.

In the past decade, numerical methods for the computational biomechanics of blood flow have progressed to overcome difficulties in diverse applications from cellular to organ scales. Such numerical methods may be classified by the type of computational mesh used for the fluid domain, into fixed mesh methods, moving mesh (boundary-fitted mesh) methods, and mesh-free methods. The type of computational mesh used is closely related to the characteristics of each method. We herein provide an overview of numerical methods recently used to simulate blood flow at macro and micro scales, with a focus on computational meshes. We also discuss recent progress in the multi-scale modeling of blood flow.

In our previous work, we developed a system named Virtual Chameleon, which provides the user with independent views for both the eyes. Visual stimuli affect the durations of alternation between dominance and suppression of cognition induced by binocular rivalry. Visual motion, spatial resolution, and visual contrast are considered as representative visual stimuli that affect the cognitive conditions induced by binocular rivalry. Therefore, we implemented a function to generate artificial saccade. In this work, we focused on visual motion for radial direction and spatial resolution. We further implemented a function to control optical zoom in the Virtual Chameleon.

We present a numerical analysis of the rheology of a dense suspension of spherical capsules in simple shear flow in the Stokes flow regime. The behaviour of neo-Hookean capsules is simulated for a volume fraction up to${\it\phi}=0.4$by graphics processing unit computing based on the boundary element method with a multipole expansion. To describe the specific viscosity using a polynomial equation of the volume fraction, the coefficients of the equation are calculated by least-squares fitting. The results suggest that the effect of higher-order terms is much smaller for capsule suspensions than rigid sphere suspensions; for example,$O({\it\phi}^{3})$terms account for only 8 % of the specific viscosity even at${\it\phi}=0.4$for capillary numbers$Ca\geqslant 0.1$. We also investigate the relationship between the deformation and orientation of the capsules and the suspension rheology. When the volume fraction increases, the deformation of the capsules increases while the orientation angle of the capsules with respect to the flow direction decreases. Therefore, both the specific viscosity and the normal stress difference increase with volume fraction due to the increased deformation, whereas the decreased orientation angle suppresses the specific viscosity, but amplifies the normal stress difference.

The deformation of a spherical capsule in oscillating shear flow is presented. The boundary element method is used to simulate the capsule motion under Stokes flow. We show that a capsule at high frequencies follows the deformation given by a leading-order prediction, which is derived from an assumption of small deformation limit. At low frequencies, on the other hand, a capsule shows an overshoot phenomenon where the maximum deformation is larger than that in steady shear flow. A larger overshoot is observed for larger capillary number or viscosity ratio. Using the maximum deformation in start-up shear flow, we evaluate the upper limit of deformation in oscillating shear flow. We also show that the overshoot phenomenon may appear when the quasi-steady orientation angle under steady shear flow is less than$9.0^{\circ }$. We propose an equation to estimate the threshold frequency between the low-frequency range, where the capsule may have an overshoot, and the high-frequency range, where the deformation is given by the leading-order prediction. The equation only includes the viscosity ratio and the Taylor parameter under simple shear flow, so it can be extended to other deformable particles, such as bubbles and drops.

Hemodynamics in microcirculation is important for hemorheology and several types of circulatory disease. Although hemodynamics research has a long history, the field continues to expand due to recent advancements in numerical and experimental techniques at the micro-and nano-scales. In this paper, we review recent computational and experimental studies of blood flow in microcirculation and microfluidics. We first focus on the computational studies of red blood cell (RBC) dynamics, from the single cellular level to mesoscopic multiple cellular flows, followed by a review of recent computational adhesion models for white blood cells, platelets, and malaria-infected RBCs, in which the cell adhesion to the vascular wall is essential for cellular function. Recent developments in optical microscopy have enabled the observation of flowing blood cells in microfluidics. Experimental particle image velocimetry and particle tracking velocimetry techniques are described in this article. Advancements in micro total analysis system technologies have facilitated flowing cell separation with microfluidic devices, which can be used for biomedical applications, such as a diagnostic tool for breast cancer or large intestinal tumors. In this paper, cell-separation techniques are reviewed for microfluidic devices, emphasizing recent advances and the potential of this fast-evolving research field in the near future.

The mechanism by which the two different heads of the ciliary outer dynein arm produce force to translocate the microtubule during beating is still unknown. In this report we use cryo-electron tomography and image processing to analyze the conformational changes and the relative abundance of each conformation of the two dynein heads from mouse respiratory cilia. In the absence of nucleotides the majority of dynein dimers are in the apo form and both heads are tightly packed, whereas they are dissociated and move independently in the presence of nucleotides. The head of the external outer arm dynein heavy chain has a diagonal shift toward both the neighboring B-tubule and the proximal end of the axoneme, while the head of the internal heavy chain shifts only longitudinally toward the proximal end. In the presence of nucleotides a significant number of the dynein dimers have two heads overlapped in the proximal shifting form or overlapped in the apo form. During ciliary bending axonemal dynein translocates microtubules by moving with short steps and two heads stay at the same position longer than cytoplasmic dynein. This demonstrates that the step of the outer arm dynein dimer is not dominated by the hand-over-hand motion, but also indicates the difference between axonemal dynein and cytoplasmic dynein. © 2014 Wiley Periodicals, Inc.

Blood is a suspension of red blood cells (RBCs) and its rheology is important when discussing the physiology of the cardiovascular system. In this study, we performed a numerical investigation of the rheological properties of an RBC suspension from the dilute to semi-dilute regime. RBCs were modelled as a capsule with a two-dimensional hyperelastic membrane. Large deformation of the thin membrane was calculated by a finite element method. Due to the small size of the RBC, fluid motion around the RBC was assumed to follow Stokes flow and was solved by a boundary element method. In the dilute limit, cell---cell interactions were omitted and the bulk stress of the suspension was calculated by the stresslet generated on a single RBC. Interestingly, the effective shear viscosity of the dilute suspension decreased with increasing viscosity of the internal liquid. In the semi-dilute regime, cells can be considered as showing pairwise interactions. The effective shear viscosity of the semi-dilute suspension shows a quadratic increase with respect to the volume fraction. These findings are important for understanding the complex phenomena of blood rheology.

Separation of certain bacteria from liquids is important in the food, water quality management, bioengineering, and pharmaceutical industries. In this study, we developed a microfluidic device for the hydrodynamic separation of motile bacteria (Escherichia coli) using drift velocity. We first investigated drift tendencies of bacteria and found that cells tended to move in a spanwise direction with similar velocities regardless of the flow rate. When the drift distance was small compared to the wetted perimeter of the cross section, the cells were not separated efficiently. We then investigated the drift phenomenon in more detail using a numerical simulation. Interestingly, the drift phenomenon was observed even without a wall boundary, indicating that drift was caused mainly by the interaction of moving cells with the background shear flow. Finally, we developed a microfluidic device to separate motile bacteria from tracer particles or less motile cells. By decreasing the channel height, the device could successfully separate motile bacteria from other particles or cells with a separation efficiency of about 40%. Connecting microchannels in a series was also found to be effective, which achieved the separation efficiency of about 60%. The knowledge obtained in this study will facilitate the development of other microfluidics devices for use with bacteria.

The diffusion of red blood cells (RBCs) in blood is important to the physiology and pathology of the cardiovascular system. In this study, we investigate flow-induced diffusion of RBCs in a semi-dilute system by calculating the pairwise interactions between RBCs in simple shear flow. A capsule with a hyperelastic membrane was used to model an RBC. Its deformation was resolved using the finite element method, whereas fluid motion inside and outside the RBC was solved using the boundary element method. The results show that shear-induced RBC diffusion is significantly anisotropic, i.e. the velocity gradient direction component is larger than the vorticity direction. We also found that the motion of RBCs during the interaction is strongly dependent on the viscosity ratio of the internal to external fluid, and the diffusivity decreases monotonically as the viscosity ratio increases. The scaling argument also suggests that the diffusivity is proportional to the shear rate and haematocrit, if the suspension is in a semi-dilute environment and the capillary number is invariant. These fundamental findings are useful to understand transport phenomena in blood flow.

Mucociliary clearance on the surface of the tracheal lumen is an important component of lung defense against dust mites and viruses. However, the axonemal structure that achieves effective ciliary motion, and the mechanisms by which discretely distributed ciliary cells generate directional flow are unknown. In this study, we examined individual ciliary motion with 7- to 9-nm spatial precision by labeling the ciliary tip with quantum dots and detected an asymmetric beating pattern. Cryo-electron tomography revealed that the densities of two inner dynein arms were missing from at least 2 doublet microtubules in the axonemal structure. Although the flow directions generated by individual ciliated cells were unsteady and diverse, the time- and space-averaged velocity field was found to be directional. These results indicate that the asymmetric ciliary motion is driven by the asymmetric axonemal structure, and it generates overall directional flow from the lungs to the oropharynx on sparsely distributed ciliated cells. From the Clinical Editor The authors of this study utilized quantum dots in determining the kinetics of ciliary motion in mouse respiratory cilia with 7- to 9-nm spatial precision.

The deformation of red blood cells in microvessels was investigated numerically for various vessel diameters, hematocrits, and shear rates. We simulated blood flow in circular channels with diameters ranging from 9 to 50 μm, hematocrits from 20% to 45%, and shear rates from 20 to 150 s(-1) using a particle-based model with parallel computing. The apparent viscosity predicted by the simulation was in good agreement with previous experimental results. We quantified the deformation of red blood cells as a function of radial position. The numerical results demonstrated that because of the shape transition in response to local shear stress and the wall effect, the radial variation of red blood cell deformation in relatively large microvessels could be classified into three different regions: near-center, middle, and near-wall regions. Effects of the local shear stress and wall varied with vessel diameter, hematocrit, and shear rate.

Microbubbles have been used in a variety of fields and have unique properties, for example shrinking collapse, long lifetime, efficient gas solubility, a negatively charged surface, and the ability to produce free radicals. In medicine, microbubbles have been used mainly as diagnostic aids to scan various organs of the body, and they have recently been investigated for use in drug and gene delivery. However, there have been no reports of blood oxygenation by use of oxygen microbubble fluids without shell reagents. In this study, we demonstrated that nano or microbubbles can achieve oxygen supersaturation of fluids, and may be sufficiently small and safe for infusion into blood vessels. Although Po(2) increases in fluids resulting from use of microbubbles were inhibited by polar solvents, normal saline solution (NSS) was little affected. Thus, NSS is suitable for production of oxygen-rich fluid. In addition, oxygen microbubble NSS effectively improved hypoxic conditions in blood. Thus, use of oxygen microbubble (nanobubble) fluids is a potentially effective novel method for oxygenation of hypoxic tissues, for infection control, and for anticancer treatment.

We developed a numerical method for large-scale simulations of cellular flow in microvessels. We employed a particle method, where all blood components were modeled using a finite number of particles. Red blood cell deformation was modeled by a spring network of membrane particles. A domain decomposition method was used for parallel implementation on distributed memory systems. In a strong scaling test up to 64 CPU cores, we obtained a linear speedup with the number of CPU cores, and demonstrated that our model can simulate O(10 3 ) red blood cells in vessels a few tens of micrometers in diameter. For quantitative validation, we analyzed the Fahraeus effect and the formation of a cell-depleted peripheral layer. Simulations were performed for tube hematocrit ranging from 20 to 45%, and microvessel diameters from 9 to 50 μm. Our numerical results were in good agreement with previous experimental results both for the discharge hematocrit and cell-depleted peripheral layer thickness.

In this paper, we propose a novel patient-specific method of modelling pulmonary airflow using graphics processing unit (GPU) computation that can be applied in medical practice. To overcome the barriers imposed by computation speed, installation price and footprint to the application of computational fluid dynamics, we focused on GPU computation and the lattice Boltzmann method (LBM). The GPU computation and LBM are compatible due to the characteristics of the GPU. As the optimisation of data access is essential for the performance of the GPU computation, we developed an adaptive meshing method, in which an airway model is covered by isotropic subdomains consisting of a uniform Cartesian mesh. We found that 4(3) size subdomains gave the best performance. The code was also tested on a small GPU cluster to confirm its performance and applicability, as the price and footprint are reasonable for medical applications.