The increasing prevalence of pulmonary ailments including asthma, chronic obstructive pulmonary disorder (COPD), lung tuberculosis and lung cancer, coupled with the success of pulmonary therapy has led to a plethora of scientific research focusing on improving the efficacy of pulmonary drug delivery systems. Recent advances in nanoscience and nanoengineering help achieve this by developing stable, potent, inhalable nano-size drug formulations that potentially increase dosages at target sites with significant therapeutic effects. In this study, we numerically analyze a novel methodology of incorporating helical air-nanoparticle streams for pulmonary nano-therapeutics, using a customized version of the open-source computational fluid dynamics (CFD) toolbox OpenFOAM. As nanoparticles predominantly follow streamlines, helical airflow transports them in a centralized core along the human upper respiratory tract, thereby minimizing deposition and hence waste on the oropharyngeal walls, potentially also reducing the risk of drug-induced toxicity in healthy tissues. Advancing our previous study on micron-particle dynamics, helical streams are shown to improve the delivery of nanodrugs, to deeper lung regions when compared to a purely axial fluid-particle jet. For example, an optimal helical stream featuring a volumetric flow rate of 30 l/min, increased the delivery of 300 nm-particles to regions beyond generation 3 by 5%, in comparison to a conventional axial jet. Results from regional deposition studies are presented, to demonstrate the robustness of helical flows in pulmonary drug delivery; thus, paving the way towards successful implementation of the novel methodology in nanotherapeutics.

This study investigates the hypothesis that by surgically manipulating the outflow graft (OG) implantation during ventricle assist device placement, it may be possible to reduce the risk of cerebral embolism. We investigate this hypothesis using a computational approach on a patient-specific basis under fully pulsatile hemodynamics with a multiscale computational fluid dynamics model incorporating a coupled Eulerian-Lagrangian scheme that effectively tracks emboli in the fluid domain. Blood is modeled as a non-Newtonian fluid based on the hematocrit level. Preliminary flow analysis shows that depending on the anastomosis angle the left ventricular assist device (LVAD) can enhance the flow to the cerebral circulation by nearly 31%. Z-test results suggest that unsteady-flow modeling ought to be an integral part of any cardiovascular simulation with residual ventricular function. Assuming unsteady-flow conditions, a shallow LVAD outflow graft anastomosis angle is the most optimal if thrombi are released from the aortic-root reducing cerebral embolization incidence to 15.5% and from the ventricle to 17%, while a more pronounced anastomosis angle becomes advantageous when particles originate from the LVAD with an embolization rate of 16.9%. Overall, computations suggest that a pronounced LVAD anastomosis angle is the better implementation. Unsteady modeling is shown to be necessary for the presence of significant antegrade aortic-root flow which induces cyclical flow patterns due to residual pulsatility. On the other hand, depending on thrombus origin and ventricular assist devices (VAD) anastomosis angle there is a strong tradeoff in embolization rates.

This study investigated impact-induced strain fields within brain tissue surrogates having different cortical gyrification. Two elastomeric surrogates, one representative of a lissencephalic brain and the other of a gyrencephalic brain, were drop impacted in unison at four different heights and in two different orientations. Each surrogate contained a radiopaque speckle pattern that was used to calculate strain fields. Two different approaches, digital image correlation (DIC) and a particle tracking method, enabled comparisons of full-field and localized strain responses. The DIC results demonstrated increased localized deviations from the mean strain field in the surrogate with a gyrified cortex. Particle tracking algorithms, defining four-node quadrilateral elements, were used to investigate the differences in the strain response of three regions: the base of a sulcus, the adjacent gyrus, and the internal capsule of the surrogates. The results demonstrated that the strains in the cortex were concentrated at the sulcal base. This mechanical mechanism of increased strain is consistent with neurodegenerative markers observed in postmortem analyses, suggesting a potential mechanism of local damage due to strain amplification at the sulcal bases in gyrencephalic brains. This strain amplification mechanism may be responsible for cumulative neurodegeneration from repeated subconcussive impacts. The observed results suggest that lissencephalic animal models, such as rodents, would not have the same modes of injury present in a gyrencephalic brain, such as that of a human. As such, a shift toward representative mild traumatic brain injury animal models having gyrencephalic cortical structures should be strongly considered.

We visualized the flow patterns in an alveolated duct model with breathing-like expanding and contracting wall motions using particle image velocimetry, and then, we investigated the effect of acinar deformation on the flow patterns. We reconstructed a compliant, scaled-up model of an alveolated duct from synchrotron microcomputed tomography images of a mammalian lung. The alveolated duct did not include any bifurcation, and its entire surface was covered with alveoli. We embedded the alveolated duct in a sealed container that was filled with fluid. We oscillated the fluid in the duct and container simultaneously and independently to control the flow and duct volume. We examined the flow patterns in alveoli, with the Reynolds number (Re) at 0.03 or 0.22 and the acinar volume change at 0%, 20%, or 80%. At the same Re, the heterogeneous deformation induced different inspiration and expiration flow patterns, and the recirculating regions in alveoli changed during respiratory cycle. During a larger acinar deformation at Re = 0.03, the flow patterns tended to change from recirculating flow to radial flow during inspiration and vice versa during expiration. Additionally, the alveolar geometric characteristics, particularly the angle between the alveolar duct and mouth, affected these differences in flow patterns. At Re = 0.22, recirculating flow patterns tended to form during inspiration and expiration, regardless of the magnitude of the acinar deformation. Our in vitro experiments suggest that the alveolated flows with nonself-similar and heterogeneous wall motions may promote particle mixing and deposition.

Determination of optimal hemodynamic and pressure–volume loading conditions for patients undergoing veno-arterial extracorporeal membrane oxygenation (VA-ECMO) would benefit from understanding the impact of ECMO flow rates ( Q E ) on the native cardiac output in the admixing zone, i.e., aortic root. This study characterizes the flow in the aortic root of a pig with severe myocardial ischemia using contrast-enhanced ultrasound particle image/tracking velocimetry (echo-PIV/PTV). New methods for data preprocessing are introduced, including autocontouring to remove surrounding tissues, followed by blind deconvolution to identify the centers of elongated bubble traces in images with low signal to noise ratio. Calibrations based on synthetic images show that this procedure increases the number of detected bubbles and reduces the error in their locations by 50%. Then, an optimized echo-PIV/PTV procedure, which integrates image enhancement with velocity measurements, is used for characterizing the time-resolved two-dimensional (2D) velocity distributions. Phase-averaged and instantaneous flow fields show that the ECMO flow rate influences the velocity and acceleration of the cardiac output during systole, and secondary flows during diastole. When Q E is 3.0 L/min or higher, the cardiac ejection velocity, phase interval with open aortic valve, velocity-time integral (VTI), and mean arterial pressure (MAP) increase with decreasing Q E , all indicating sufficient support. For lower Q E , the MAP and VTI decrease as Q E is reduced, and the deceleration during transition to diastole becomes milder. Hence, for this specific case, the optimal ECMO flow rate is 3.0 L/min.

The lymphatic system plays a pivotal role in the transport of fats, waste, and immune cells, while also serving as a metastatic route for select cancers. Using live imaging and particle tracking, we experimentally characterized the lymph flow field distal from the inguinal lymph node in the vicinity of normal bileaflet and malformed unileaflet intraluminal valves. Particle tracking experiments demonstrated that intraluminal lymphatic valves concentrate higher velocity lymph flow in the center of the vessel, while generating adjacent perivalvular recirculation zones. The recirculation zones are characterized by extended particle residence times and low wall shear stress (WSS) magnitudes in comparison to the rest of the lymphangion. A malformed unileaflet valve skewed lymph flow toward the endothelium on the vessel wall, generating a stagnation point and a much larger recirculation zone on the opposite wall. These studies define physical consequences of bileaflet and unileaflet intraluminal lymphatic valves that affect lymph transport and the generation of a heterogeneous flow field that affects the lymphatic endothelium nonuniformly. The characterized flow fields were recreated in vitro connecting different flow environments present in the lymphangion to a lymphatic endothelial cell (LEC) pro-inflammatory phenotype. Unique and detailed insight into lymphatic flow is provided, with potential applications to a variety of diseases that affect lymph transport and drug delivery.

Density and mechanical properties (e.g., compressibility or bulk modulus) are important cellular biophysical markers. As such, developing a method to separate cells directly based on these properties can benefit various applications including biological research, diagnosis, prognosis, and therapeutics. As a potential solution, surface acoustic wave (SAW)-based cell separation has demonstrated advantages in terms of biocompatibility and compact device size. However, most SAW-reliant cell separations are achieved using an entangled effect of density, various mechanical properties, and size. In this work, we demonstrate SAW-based separation of cells/particles based on their density and compressibility, irrespective of their sizes, by manipulating the acoustic properties of the fluidic medium. Using our platform, SAW-based separation is achieved by varying the dimensions of the microfluidic channels, the wavelengths of acoustic signals, and the properties of the fluid media. Our method was applied to separate paraformaldehyde-treated and fresh Hela cells based on differences in mechanical properties; a recovery rate of 85% for fixed cells was achieved. It was also applied to separate red blood cells (RBCs) and white blood cells (WBCs) which have different densities. A recovery rate of 80.5% for WBCs was achieved.

Animal skeletal muscle exhibits very interesting behavior at near-stall forces (when the muscle is loaded so strongly that it can barely contract). Near this physical limit, the myosin II proteins may be unable to reach advantageous actin binding sites through simple attractive forces. It has been shown that the advantageous utilization of thermal agitation is a likely source for an increased force-production capacity and reach in myosin-V (a processing motor protein), and here we explore the dynamics of a molecular motor without hand-over-hand motion including Brownian motion to show how local elastic energy well boundaries may be overcome. We revisit a spatially two-dimensional mechanical model to illustrate how thermal agitation can be harvested for useful mechanical work in molecular machinery inspired by this biomechanical phenomenon without rate functions or empirically inspired spatial potential functions. Additionally, the model accommodates variable lattice spacing, and it paves the way for a full three-dimensional model of cross-bridge interactions where myosin II may be azimuthally misaligned with actin binding sites. With potential energy sources based entirely on realizable components, this model lends itself to the design of artificial, molecular-scale motors.

Clinical success of extracorporeal membrane oxygenation (ECMO) depends on the proper venous cannulation. Venovenous (VV) ECMO is the preferred clinical intervention as it provides a single-site access by utilizing a VV double lumen cannula (VVDLC) with a higher level of mobilization and physical rehabilitation. Concurrent venous blood drainage and oxygenated blood infusion in the right atrium at the presence of the cannula makes the flow dynamics complex where potential mixing of venous and oxygenated blood can drastically decrease the overall performance of ECMO. There are no studies focusing on the neonatal and pediatric populations, in which the flow related effects are critical due to the small atrium size. In this study, fluid dynamics of infusion outflow jet for two commercially available neonatal VVDLC is analyzed using particle image velocimetry (PIV). Moreover, six new designs are proposed for the infusion channel geometry and compared. Important flow parameters such as flow turning angle (FTA), velocity decay, potential core, and turbulent intensity are investigated for the proposed models. The experiments showed that the outflow parameters of commercial cannulae such as FTA are strongly dependent on the operating Re number. This may result in a drastic efficiency reduction for cannula operating at off-design flow conditions. Moreover, the infusion outlet tip structure and jet internal guiding pathway (JIGP) was observed to greatly affect the outflow flow features. This is of paramount importance since the anatomical positioning of the cannula and the infusion outlet is strongly dependent on the outflow properties such as FTA.

The Fontan procedure is a successful palliation for single ventricle defect. Yet, a number of complications still occur in Fontan patients due to abnormal blood flow dynamics, necessitating improved flow analysis and treatment methods. Phase-contrast magnetic resonance imaging (MRI) has emerged as a suitable method for such flow analysis. However, limitations on altering physiological blood flow conditions in the patient while in the MRI bore inhibit experimental investigation of a variety of factors that contribute to impaired cardiovascular health in these patients. Furthermore, resolution and flow regime limitations in phase contrast (PC) MRI pose a challenge for accurate and consistent flow characterization. In this study, patient-specific physical models were created based on nine Fontan geometries and MRI experiments mimicking low- and high-flow conditions, as well as steady and pulsatile flow, were conducted. Additionally, a particle image velocimetry (PIV)-compatible Fontan model was created and flow was analyzed with PIV, arterial spin labeling (ASL), and four-dimensional (4D) flow MRI. Differences, though nonstatistically significant, were observed between flow conditions and between patient-specific models. Large between-model variation supported the need for further improvement for patient-specific modeling on each unique Fontan anatomical configuration. Furthermore, high-resolution PIV and flow-tracking ASL data provided flow information that was not obtainable with 4D flow MRI alone.

This study explores the optimal left ventricular assist device (LVAD) cannula outflow configuration in a patient-specific replica of the aorta. The volumetric velocity field is measured using phase-contrast magnetic resonance imaging (PC-MRI) under a physiologically relevant steady flow. The effect of the LVAD outflow graft insertion site and anastomosis angle on the transport of embolic particles to cranial vessels is studied by solving the particle equation of motion for spheres in the range of 0.1–1.0 mm using the measured three-dimensional (3D) velocity field. Results show that for a given aorta anatomy, it is possible to design the cannula graft location and terminal curvature so that the probability of embolic transport to the cranial vessels is significantly minimized. This is particularly important since the complex flow pattern in each cannula case affects the embolic trajectories differently, and hence the common assumption that particles distribute by the volumetric flow division does not hold.

In engineering and medicine, there is a growing interest in using textiles made of composites with enhanced thermal properties. One such type of textile is fabric impregnated with ceramics and mineral particles. This material has high emissivity in the infrared range and may have therapeutic benefits for treatments of diseases, like Raynaud's syndrome. While there is significant clinical and commercial interest, there is an evident lack of fundamental studies on the heat transfer aspects of these fabrics. The goal of this technical brief is to present results from a fundamental study examining the thermal effects of fabric with ceramics and minerals (produced by Nanobionic, Inc., Athens, Greece) on the temperatures of the hands. With a confidence level of 90%, the results show that the textile with ceramics and minerals has an enhanced thermal effect on warming a cold hand in comparison to a placebo fabric without ceramics or minerals. Much more research is needed to increase the level of confidence and develop a fundamental understanding of the mechanism.

Adhesion of carrier particles to the luminal surface of endothelium under hemodynamic flow conditions is critical for successful vascular drug delivery. Endothelial cells (ECs) line the inner surface of blood vessels. The effect of mechanical behavior of this compliant surface on the adhesion of blood-borne particles is unknown. In this contribution, we use a phase-plane method, first developed by Hammer and Lauffenburger (1987, “A Dynamical Model for Receptor-Mediated Cell Adhesion to Surfaces,” Biophys. J., 52 (3), p. 475), to analyze the stability of specific adhesion of a spherical particle to a compliant interface layer. The model constructs a phase diagram and predicts the state of particle adhesion, subjected to an incident simple shear flow, in terms of interfacial elasticity, shear rate, binding affinity of cell adhesive molecules, and their surface density. The main conclusion is that the local deformation of the flexible interface inhibits the stable adhesion of the particle. In comparison with adhesion to a rigid substrate, a greater ligand density is required to establish a stable adhesion between a particle and a compliant interface.

Wearable sensors embedded with inertial measurement units have become commonplace for the measurement of head impact biomechanics, but individual systems often suffer from a lack of measurement fidelity. While some researchers have focused on developing highly accurate, single sensor systems, we have taken a parallel approach in investigating optimal estimation techniques with multiple noisy sensors. In this work, we present a sensor network methodology that utilizes multiple skin patch sensors arranged on the head and combines their data to obtain a more accurate estimate than any individual sensor in the network. Our methodology visually localizes subject-specific sensor transformations, and based on rigid body assumptions, applies estimation algorithms to obtain a minimum mean squared error estimate. During mild soccer headers, individual skin patch sensors had over 100% error in peak angular velocity magnitude, angular acceleration magnitude, and linear acceleration magnitude. However, when properly networked using our visual localization and estimation methodology, we obtained kinematic estimates with median errors below 20%. While we demonstrate this methodology with skin patch sensors in mild soccer head impacts, the formulation can be generally applied to any dynamic scenario, such as measurement of cadaver head impact dynamics using arbitrarily placed sensors.

Ventricular assist devices (VADs) are implanted in patients with a diseased ventricle to maintain peripheral perfusion as a bridge-to-transplant or as destination therapy. However, some patients with continuous flow VADs (e.g., HeartMate II (HMII)) have experienced gastrointestinal (GI) bleeding, in part caused by the proteolytic cleavage or mechanical destruction of von Willebrand factor (vWF), a clotting glycoprotein. in vitro studies were performed to measure the flow located within the HMII outlet cannula under both steady and physiological conditions using particle image velocimetry (PIV). Under steady flow, a mock flow loop was used with the HMII producing a flow rate of 3.2 L/min. The physiological experiment included a pulsatile pump operated at 105 BPM with a ventricle filling volume of 50 mL and in conjunction with the HMII producing a total flow rate of 5.0 L/min. Velocity fields, Reynolds normal stresses (RNSs), and Reynolds shear stresses (RSSs) were analyzed to quantify the outlet flow's potential contribution to vWF degradation. Under both flow conditions, the HMII generated principal Reynolds stresses that are, at times, orders of magnitude higher than those needed to unfurl vWF, potentially impacting its physiological function. Under steady flow, principal RNSs were calculated to be approximately 500 Pa in the outlet cannula. Elevated Reynolds stresses were observed throughout every phase of the cardiac cycle under physiological flow with principal RNSs approaching 1500 Pa during peak systole. Prolonged exposure to these conditions may lead to acquired von Willebrand syndrome (AvWS), which is accompanied by uncontrollable bleeding episodes.

Contrast ultrasound is a widely used clinical tool to obtain real-time qualitative blood flow assessments in the heart, liver, etc. Echocardiographic particle image velocimetry (echo-PIV) is a technique for obtaining quantitative velocity maps from contrast ultrasound images. However, unlike optical particle image velocimetry (PIV), routine echo images are prone to nonuniform spatiotemporal variations in tracer distribution, making analysis difficult for standard PIV algorithms. This study introduces optimized procedures that integrate image enhancement, PIV, and particle tracking velocimetry (PTV) to obtain reliable time-resolved two-dimensional (2D) velocity distributions. During initial PIV analysis, multiple results are obtained by varying processing parameters. Optimization involving outlier removal and smoothing is used to select the correct vector. These results are used in a multiparameter PTV procedure. To demonstrate their clinical value, the procedures are implemented to obtain velocity and vorticity distributions over multiple cardiac cycles using images acquired from four left ventricular thrombus (LVT) patients. Phase-averaged data elucidate flow structure evolution over the cycle and are used to calculate penetration depth and strength of left ventricular (LV) vortices, as well as apical velocity induced by them. The present data are consistent with previous time-averaged results for the minimum vortex penetration depth associated with LVT occurrence. However, due to decay and fragmentation of LV vortices, as they migrate away from the mitral annulus, in two cases with high penetration, there is still poor washing near the resolved clot throughout the cycle. Hence, direct examination of entire flow evolution may be useful for assessing risk of LVT relapse before prescribing anticoagulants.

Viewed in renal physiology as a refined filtration device, the glomerulus filters large volumes of blood plasma while keeping proteins within blood circulation. Effects of macromolecule size and macromolecule hydrodynamic interaction with the nanostructure of the cellular layers of the glomerular capillary wall on the glomerular size selectivity are investigated through a mathematical simulation based on an ultrastructural model. The epithelial slit, a planar arrangement of fibers connecting the epithelial podocytes, is represented as a row of parallel cylinders with nonuniform spacing between adjacent fibers. The mean and standard deviation of gap half-width between its fibers are based on values recently reported from electron microscopy. The glomerular basement membrane (GBM) is represented as a fibrous medium containing fibers of two different sizes: the size of type IV collagens and that of glycosaminoglycans (GAGs). The endothelial cell layer is modeled as a layer full of fenestrae that are much larger than solute size and filled with GAGs. The calculated total sieving coefficient agrees well with the sieving coefficients of ficolls obtained from in vivo urinalysis in humans, whereas the computed glomerular hydraulic permeability also falls within the range estimated from human glomerular filtration rate (GFR). Our result indicates that the endothelial cell layer and GBM significantly contribute to solute and fluid restriction of the glomerular barrier, whereas, based on the structure of the epithelial slit obtained from electron microscopy, the contribution of the epithelial slit could be smaller than previously believed.

Red blood cells (RBCs) are the most abundant cellular element suspended in blood. Together with the usual biconcave-shaped RBCs, i.e., discocytes, unusual-shaped RBCs are also observed under physiological and experimental conditions, e.g., stomatocytes and echinocytes. Stomatocytes and echinocytes are formed from discocytes and in addition can revert back to being discocytes; this shape change is known as the stomatocyte–discocyte–echinocyte (SDE) transformation. To-date, limited research has been conducted on the numerical prediction of the full SDE transformation. Spring-particle RBC (SP-RBC) models are commonly used to numerically predict RBC mechanics and rheology. However, these models are incapable of predicting the full SDE transformation because the typically employed bending model always leads to numerical instability with severely deformed shapes. In this work, an enhanced SP-RBC model is proposed in order to extend the capability of this model type and so that the full SDE transformation can be reproduced. This is achieved through the leveraging of an advanced bending model. Transformed vesicle and RBC shapes are predicted for a range of reduced volume and reduced membrane area difference (MAD), and very good agreement is obtained in the comparison of predicted shapes with experimental observations. Through these predictions, vesicle and SDE transformation phase diagrams are developed and, importantly, in the SDE case, shape boundaries are proposed for the first time relating RBC shape categories to RBC reduced volume and reduced MAD.

Detailed blood velocity map in the vascular system can be obtained by applying the optical flow method (OFM) in processing fluoroscopic digital subtracted catheter angiographic images; however, there are still challenges with the accuracy of this method. In the present study, a divergence compensatory optical flow method (DC-OFM), in which a nonzero divergence of velocity is assumed due to the finite resolution of the image, was explored and applied to the digital subtraction angiography (DSA) images of blood flow. The objective of this study is to examine the applicability and evaluate the accuracy of DC-OFM in assessing the blood flow velocity in vessels. First, an Oseen vortex flow was simulated on the standard particle image to generate an image pair. Then, the DC-OFM was applied on the particle image pair to recover the velocity field for validation. Second, DSA images of intracranial arteries were used to examine the accuracy of the current method. For each set of images, the first image is the in vivo DSA image, and the second image is generated by superimposing a given flow field. The recovered velocity map by DC-OFM agrees well with the exact velocity for both the particle images and the angiographic images. In comparison with the traditional OFM, the present method can provide more accurate velocity estimation. The accuracy of the velocity estimation can also be improved by implementing preprocess techniques including image intensification, Gaussian filtering, and “image-shift.”

We review recent advances in multiscale modeling of the biomechanical characteristics of red blood cells (RBCs) in hematological diseases, and their relevance to the structure and dynamics of defective RBCs. We highlight examples of successful simulations of blood disorders including malaria and other hereditary disorders, such as sickle-cell anemia, spherocytosis, and elliptocytosis.