The major problem in understanding the therapeutically targeted drug delivery system in the deeper airways of the human lung is the lack of adequate data of particle transport and deposition (TD) in ...the transitional and respiratory zones (deeper airways) of the human lung. An understanding of the morphometry of the pulmonary airways and the lungs forms the primary step in a study of pulmonary aerosol deposition. The present study is the first-ever approach to explore the pulmonary aerosol TD in a digital 17-generation human pulmonary airway model. The present numerical study achieved the lack of the particle TD data in the deeper airways of the human lung. This paper presents a 3-D (3-dimensional) CFD (Computational Fluid Dynamics) study of an anatomically realistic 17-generation lung bronchial tree model based on the high-resolution computer tomography (HRCT) data by Schmidt et al. (2004). Physical morphometry is necessary for sufficiently calculating air and particle dynamics in human pulmonary airways with available data on a large number of generations. A Lagrangian-based Discrete Phase Model (DPM) is used to study the particle TD in the 17-generation of the lung airways. The numerical results demonstrate that inertial impaction is dominant in the upper airways and a large percentage of particles is deposited in the upper airways. The numerical results also illustrate that a large percentage of smaller diameter particles leaves through the airway outlet boundary at the 17th generation irrespective of breathing patterns. The escaped particles are considered to continue to follow the airway flow field further downstream after the 17th generation till the 23rd generation and some of them will reach the alveolar sacs region. This computational model could potentially aid in overcoming the nanobiotechnology toxicity problem for drug delivery in the deeper airways.
•Advanced numerical model for micro-particle TD in the human lung is developed.•This study is conducted for 17-generation lung geometry for the first time.•The particle diameter effects are investigated for different breathing conditions.•This study will help pharmaceutical companies to design new drug delivery tools.
An improved red blood cell (RBC) membrane model is developed based on the bilayer coupling model (BCM) to accurately predict the complete sequence of stomatocyte-discocyte-echinocyte (SDE) ...transformation of a RBC. The coarse-grained (CG)-RBC membrane model is proposed to predict the minimum energy configuration of the RBC from the competition between lipid-bilayer bending resistance and cytoskeletal shear resistance under given reference constraints. In addition to the conventional membrane surface area, cell volume and bilayer-leaflet-area-difference constraints, a new constraint: total-membrane-curvature is proposed in the model to better predict RBC shapes in agreement with experimental observations. A quantitative evaluation of several cellular measurements including length, thickness and shape factor, is performed for the first time, between CG-RBC model predicted and three-dimensional (3D) confocal microscopy imaging generated RBC shapes at equivalent reference constraints. The validated CG-RBC membrane model is then employed to investigate the effect of reduced cell volume and elastic length scale on SDE transformation, to evaluate the RBC deformability during SDE transformation, and to identify the most probable RBC cytoskeletal reference state. The CG-RBC membrane model can predict the SDE shape behaviour under diverse shape-transforming scenarios, in-vitro RBC storage, microvascular circulation and flow through microfluidic devices.
This study aims to design and optimize an organic Rankine cycle (ORC) and radial inflow turbine to recover waste heat from a polymer exchange membrane (PEM) fuel cell. ORCs can take advantage of ...low-quality waste heat sources. Developments in this area have seen previously unusable, small waste heat sources become available for exploitation. Hydrogen PEM fuel cells operate at low temperatures (70 °C) and are in used in a range of applications, for example, as a balancing or backup power source in renewable hydrogen plants. The efficiency of an ORC is significantly affected by the source temperature and the efficiency of the expander. In this case, a radial inflow turbine was selected due to the high efficiency in ORCs with high density fluids. Small scale radial inflow turbines are of particular interest for improving the efficiency of small-scale low temperature cycles. Turbines generally have higher efficiency than positive displacement expanders, which are typically used. In this study, the turbine design from the mean-line analysis is also validated against the computational fluid dynamic (CFD) simulations conducted on the optimized machine. For the fuel cell investigated in this study, with a 5 kW electrical output, a potential additional 0.7 kW could be generated through the use of the ORC. The ORC’s output represents a possible 14% increase in performance over the fuel cell without waste heat recovery (WHR).
The atmospheric particles from different sources, and the therapeutic particles from various drug delivery devices, exhibit a complex size distribution, and the particles are mostly polydisperse. The ...limited available in vitro, and the wide range of in silico models have improved understanding of the relationship between monodisperse particle deposition and therapeutic aerosol transport. However, comprehensive polydisperse transport and deposition (TD) data for the terminal airways is still unavailable. Therefore, to benefit future drug therapeutics, the present numerical model illustrates detailed polydisperse particle TD in the terminal bronchioles for the first time. Euler-Lagrange approach and Rosin-Rammler diameter distribution is used for polydisperse particles. The numerical results show higher deposition efficiency (DE) in the right lung. Specifically, the larger the particle diameter (d
> 5 μm), the higher the DE at the bifurcation area of the upper airways is, whereas for the smaller particle (d
< 5 μm), the DE is higher at the bifurcation wall. The overall deposition pattern shows a different deposition hot spot for different diameter particle. These comprehensive lobe-specific polydisperse particle deposition studies will increase understanding of actual inhalation for particle TD, which could potentially increase the efficiency of pharmaceutical aerosol delivery at the targeted position of the terminal airways.
Red blood cells (RBCs) deform significantly and repeatedly when passing through narrow capillaries and delivering dioxygen throughout the body. Deformability of RBCs is a key characteristic, largely ...governed by the mechanical properties of the cell membrane. This study investigated RBC mechanical properties using atomic force microscopy (AFM) with the aim to develop a coarse-grained particle method model to study for the first time RBC indentation in both 2D and 3D. This new model has the potential to be applied to further investigate the local deformability of RBCs, with accurate control over adhesion, probe geometry and position of applied force.
The model considers the linear stretch capacity of the cytoskeleton, bending resistance and areal incompressibility of the bilayer, and volumetric incompressibility of the internal fluid. The model's performance was validated against force-deformation experiments performed on RBCs under spherical AFM indentation. The model was then used to investigate the mechanisms which absorbed energy through the indentation stroke, and the impact of varying stiffness coefficients on the measured deformability. This study found the membrane's bending stiffness was most influential in controlling RBC physical behaviour for indentations of up to 200 nm.
As the bilayer provides bending resistance, this infers that structural changes within the bilayer are responsible for the deformability changes experienced by deteriorating RBCs. The numerical model presented here established a foundation for future investigations into changes within the membrane that cause differences in stiffness between healthy and deteriorating RBCs, which have already been measured experimentally with AFM.
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