@article{sridhar_chari_kleinstreuer_2023, title={A computational study of droplet-spray formation from pressurized metered dose inhalers with applications to drug deposition in a human lung-airway model}, ISSN={["1521-7388"]}, DOI={10.1080/02786826.2023.2189927}, abstractNote={Abstract Orally administered drugs using portable devices, such as pressurized metered dose inhalers (pMDIs), can alleviate the symptoms of various respiratory diseases. The basic non-isothermal fluid-particle dynamics of pMDIs have been simulated, including computer model validations and different inhalation techniques, using the Ventolin HFA from GlaxoSmithKline (UK) as a representative application. Specifically, the evolution of thermal droplet sprays has been realistically simulated and experimentally validated, employing the open-source computational fluid dynamics (CFD) toolbox OpenFOAM. The segmental droplet temperature results show elevated temperatures for higher inhalation flow rates because of stronger convective flow around the evaporating droplets. The general problems of high, wasteful oropharyngeal deposition and cold impacting droplets were tackled by devising a new ‘pulsed injection’ strategy in which the spray was broken into pulses with a time delay between them. This new methodology indicated up to a 20% increase in useful lung deposition beyond the oropharynx over conventional drug administration methods. In addition, compared to the conventional single injection approach, the segmental variations in temperature of the deposited aerosols show an increase in temperature of around 10% and 7% for the 30 LPM and 60 LPM cases up to segment 4 for pulsed injection. An increase of 23% and 13% for the 30 LPM and 60 LPM cases were observed for segments 5–7 for pulsed injection. Also, a reduction in inertia of the droplets at 30 LPM, where the spray was broken into eight pulses with 100 ms delay between them, resulted in higher residence times and an increase in temperature of over Copyright © 2023 American Association for Aerosol Research}, journal={AEROSOL SCIENCE AND TECHNOLOGY}, author={Sridhar, Karthik and Chari, Sriram and Kleinstreuer, Clement}, year={2023}, month={Mar} } @article{dave_kleinstreuer_chari_2022, title={An effective PBPK model predicting dissolved drug transfer from a representative nasal cavity to the blood stream}, volume={160}, ISSN={["1879-1964"]}, DOI={10.1016/j.jaerosci.2021.105898}, abstractNote={Predicting the fate of nasally administered drugs is important for the understanding and possible improvement of in vivo performance. When computational fluid-particle dynamics (CFPD) results are coupled with a physiologically based pharmacokinetic (PBPK) model, drug concentrations in the blood stream can be obtained. Specifically, hybrid CFPD-PBPK simulations can predict inhaled particle transport, deposition, and uptake in the nasal mucus layers and subsequently absorbed drug migration from the nasal cavity to the blood stream.The computer simulation results of Chari et al. (2021) were used as input to a basic PBPK model to track the deposited and dissolved drugs from the nasal cavities to the blood stream. Employing the open-source toolbox OpenFOAM, our PBPK model predictions were compared with experimental in vivo data sets for different corticosteroids. The relative differences between experimental and simulated values of PK metrics, following administration of mometasone furoate nasal spray, were all 7% or less. Drug plasma concentrations based on different drug parameters, such as solubility and partition coefficient, were studied as well. The drug concentration in the plasma was found to increase with an increase in drug solubility (Cs = 0.02 mg/ml, 0.1 mg/ml, 0.2 mg/ml). The same trend was observed for different partition coefficients (Kow = 5e-3, 2, 5000), where the plasma concentration curve peaked for a partition coefficient of 5000. It was also observed that drug dosage controls the amount of residual drug concentrations in the plasma with the passage of time. Two different drug dosages were studied, ie, 50 μg and 800 μg, with the former being completely absorbed in the plasma after 8 h; however, in the latter case the drug was not completely absorbed after that time interval. These modeling and simulation results are useful for planning aspects in drug development, as the predictions provide physical insight to differences in device, formulation, and dosage selection.}, journal={JOURNAL OF AEROSOL SCIENCE}, author={Dave, Sujal and Kleinstreuer, Clement and Chari, Sriram}, year={2022}, month={Feb} } @article{gurumurthy_kleinstreuer_2022, title={Analysis of improved oral drug delivery with different helical stream inhalation modes}, volume={141}, ISSN={["1879-0534"]}, DOI={10.1016/j.compbiomed.2021.105132}, abstractNote={A challenging aspect of pulmonary drug delivery devices, e.g., metered dose inhalers (MDIs), is to deliver therapeutic drugs to prescribed target locations at the required dosage level. In this study, validated computer simulations of micron-drug inhalation with angled or radially positioned helical fluid-particle streams are simulated and analyzed. For a suitable swirl number significant improvements in drug delivery, especially to deeper lung regions, have been achieved. Specifically, considering realistic polydisperse particle distributions at the mouth inlet for a subject-specific upper lung airway geometry, a 10-degree angled helical stream increased the local efficacy by up to 26% in comparison to a conventional helical stream, causing an overall dosage of about 60% to the deep lung. Considering lobe-specific drug targeting scenarios, while using an off-center, i.e., radially well positioned, helical-flow mouthpiece, the local particle-deposition efficacy increased from 9% to 24% in the left lobe and from 25% to 38% in the right lobe in comparison to conventional drug-aerosol stream released from the central position. The efficacy of helical streams for pulmonary drug delivery applications has been established.}, journal={COMPUTERS IN BIOLOGY AND MEDICINE}, author={Gurumurthy, Adithya and Kleinstreuer, Clement}, year={2022}, month={Feb} } @article{chari_sridhar_kleinstreuer_2022, title={Effects of subject-variability on nasally inhaled drug deposition, uptake, and clearance}, volume={165}, ISSN={["1879-1964"]}, DOI={10.1016/j.jaerosci.2022.106021}, abstractNote={Accurate and realistic predictions of the fate of nasally inhaled generic drugs provide new physical insight which can be of great importance to toxicologists, drug developers and federal regulators alike. To understand the dynamics of mucociliary clearance (MCC) and subsequent absorption of the dissolved drug by the nasal epithelium, it becomes necessary to model the air-particle-mucus dynamics accurately. The MCC process, including particle dissolution, transport and absorption for a 3-D representative nasal cavity, were established by Chari et al. (2021). In this study, the effects of inter-subject variability of three representative nasal cavities (subjects A, B, C) on deposition and subsequent uptake of the dissolved drug in the nasal epithelium are analyzed for three generic drugs: Mometasone furoate (MF), Flunisolide (FN), and Ribavirin (RB). The computational fluid-particle dynamics (CF-PD) results indicate that smaller sized particles (3 μm) deposit more in the ciliated portion of the nasal cavity where the columnar cells responsible for uptake are present. In contrast, larger particles (10 μm) tend to deposit in the unciliated anterior third of the nose. The epithelial uptake in case of subject A was considerably higher than that in subjects B and C because of the unique anatomical characteristics of subject A. Also, FN and RB were found to have a higher rate of uptake compared to MF due to their considerably higher partition coefficient. As a visualization tool, concentration contours are used to explain regional trends in cumulative drug uptake for all three cases. • The open-source CFD toolbox, OpenFOAM, has been employed for the development of the computer simulation model. • This study illustrates the effects of inter-subject variability on deposition, dissolution and uptake of 3 generic drugs in representative nasal cavity models. • Smaller particles, with their relatively large surface area, tend to dissolve quicker and are absorbed more rapidly than larger particles. • Particles deposited closer to the ciliated portion of the nasal cavity are more readily absorbed when compared to particles deposited closer to the unciliated nasal vestibule.}, journal={JOURNAL OF AEROSOL SCIENCE}, author={Chari, Sriram and Sridhar, Karthik and Kleinstreuer, Clement}, year={2022}, month={Sep} } @article{vachhani_kleinstreuer_2021, title={Comparison of micron- and nano-particle transport in the human nasal cavity with a focus on the olfactory region}, volume={128}, ISSN={["1879-0534"]}, DOI={10.1016/j.compbiomed.2020.104103}, abstractNote={Intranasal administration of drugs serves as a promising, noninvasive option for the treatment of various disorders of the central nervous system and upper respiratory tract. Predictive, ie, realistic and accurate, particle tracking in the human nasal cavities is an essential step to achieve these goals. The major factors affecting aerosol transport and deposition are the inhalation flowrate, the particle characteristics, and the nasal airway geometry. In vivo and in vitro studies using nasal cavity casts provide realistic images regarding particle-deposition pattern. Computational Fluid-Particle Dynamics (CF-PD) studies can offer a flexible, detailed and cost effective solution to the problem of direct drug delivery. The open-source software OpenFOAM was employed to conduct, after model validation, laminar and turbulent fluid-particle dynamics simulations for representative nasal cavities. Specifically, micron particles and nanoparticles were both individually tracked for different steady airflow rates to determine sectional deposition efficiencies. For micron particles, inertial forces were found to be the dominating factor, resulting in higher deposition for larger particles, mainly due to impaction. In contrast, diffusional effects are more important for nanoparticles. With a focus on the olfactory region, the detailed analysis of sectional deposition concentrations, considering a wide range of particle diameters, provide new physical insight to the particle dynamics inside human nasal cavities. The laminar/turbulent Euler-Lagrange modelling approach for simulating the fate of nanoparticles form a foundation for future studies focusing on targeted drug delivery. A major application would be direct nanodrug delivery to the olfactory region to achieve large local concentrations for possible migration across the blood-brain-barrier.}, journal={COMPUTERS IN BIOLOGY AND MEDICINE}, author={Vachhani, Shantanu and Kleinstreuer, Clement}, year={2021}, month={Jan} } @article{chari_sridhar_walenga_kleinstreuer_2021, title={Computational analysis of a 3D mucociliary clearance model predicting nasal drug uptake}, volume={155}, ISSN={["1879-1964"]}, DOI={10.1016/j.jaerosci.2021.105757}, abstractNote={Accurate and realistic predictions of the fate of nasally inhaled drugs help to understand the complex fluid-particle dynamics in the nasal cavity. Key elements of such a comprehensive numerical analysis include: (i) inhaled drug-aerosol transport and deposition with air-particle-mucus interactions; and (ii) mucociliary clearance (MCC) dynamics, including drug transport, dissolution and absorption for different nasal inlet conditions. The open-source computational fluid dynamics (CFD) toolbox, OpenFOAM, has been employed for the development of the computer simulation model. As part of the design, a novel 3D meshing technique allows for the smooth capture of both the relatively large flow domain as well as the micron-size mucus layer. This efficient meshing strategy drastically reduces the overall meshing time from hours to a matter of minutes. The effect of pharmacokinetic characteristics of drugs on dissolution, subsequent uptake and clearance were analyzed. A method to impose a boundary-driven flow velocity was introduced in order to mimic the beating of the cilia. Several drug specific parameters, such as solubility, partition coefficient and particle size, were considered. The effects of particle distribution on MCC and uptake were simulated as well. The CFD predictions show that drugs with a high partition coefficient are absorbed rapidly. Similarly, drugs with higher solubility show an appreciable increase in cumulative uptake in the epithelium. Particle size, however, plays a more nuanced role in drug uptake. Specifically, smaller particles with their relatively large surface areas, tend to dissolve quicker and are absorbed more rapidly when compared to larger particles. However, after the initial steeper increase in cumulative uptake of the smaller particles, the difference in the uptake values for the two cases is negligible. Furthermore, the initial deposition locations in the nasal cavity play an important role in overall drug uptake. Particles deposited closer to the ciliated portion of the nasal cavity (i.e. the posterior region) were more readily absorbed when compared to particles deposited closer to the unciliated nasal vestibule.}, journal={JOURNAL OF AEROSOL SCIENCE}, author={Chari, Sriram and Sridhar, Karthik and Walenga, Ross and Kleinstreuer, Clement}, year={2021}, month={Jun} } @book{kleinstreuer_2021, place={New York}, title={Essentials of Engineering Thermodynamics: Principles and Applications}, publisher={McGraw-Hill Education}, author={Kleinstreuer, C.}, year={2021} } @article{gurumurthy_kleinstreuer_2021, title={Helical fluid-particle flow dynamics for controlling micron-particle deposition in a representative human upper lung-airway model}, volume={151}, ISSN={["1879-1964"]}, DOI={10.1016/j.jaerosci.2020.105656}, abstractNote={The transport and deposition of inhaled micron particles is largely determined by their inlet conditions, breathing rate, and the individual airway geometry. In this study, helical air-particle flow is introduced, which significantly affects the particle dynamics with applications to targeted drug delivery. Specifically, helical flow, which reduces axial momentum, can be controlled by varying the swirl number and hence the characteristics of the fluid-particle stream. In case of drug-aerosol delivery, the waste of inhaled drugs in the human upper respiratory tract due to inertial impaction can be mitigated by implementing a controlled helical flow with a modified inhaler. For example, 2 μm-particle deposition was reduced in the oral cavity for a helical fluid-particle stream with 10 l/min inhalation by 39.7% when the swirl number was increased from 0 to 0.6. Considering a 30 l/min inhalation flow rate, the deposition fraction of 2 μm-particles in the oral cavity was reduced by 73.5% as the swirl number increased from 0 to 2. A new non-dimensional parameter called the swirl number threshold (Sth), is also discussed, which is useful in assessing the impact of helical streams in drug-aerosol delivery. All computer experiments were performed with an enhanced version of the open-source computational fluid dynamics toolbox OpenFOAM.}, journal={JOURNAL OF AEROSOL SCIENCE}, author={Gurumurthy, Adithya and Kleinstreuer, Clement}, year={2021}, month={Jan} } @article{gurumurthy_kleinstreuer_2021, title={Improving Pulmonary Nanotherapeutics Using Helical Aerosol Streams: An In Silico Study}, volume={143}, ISSN={["1528-8951"]}, DOI={10.1115/1.4051217}, abstractNote={Abstract}, number={11}, journal={JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME}, author={Gurumurthy, Adithya and Kleinstreuer, Clement}, year={2021}, month={Nov} } @article{vachhani_kleinstreuer_2021, title={Numerical analysis of enhanced nano-drug delivery to the olfactory bulb}, ISSN={["1521-7388"]}, DOI={10.1080/02786826.2021.1959018}, abstractNote={Abstract Central Nervous System (CNS) disorders are one of the major causes of fatalities in the world today. Thus, it is essential to transport a considerable amount of drugs to a specific brain location for any treatment to be effective. A noninvasive approach is direct nanodrug delivery via the nasal route. The main pathway for these drugs into the brain requires crossing the Blood-Brain Barrier (BBB), located along the olfactory region of the nasal cavity. Tight junctions of the BBB allow only nanoparticles of sufficiently high concentrations to pass through. Multifunctional nanoparticles can be used to target the brain via the olfactory bulb. Computational Fluid-Particle Dynamics (CF-PD) simulations offer a manageable, accurate and cost-effective route for studying this possibility. For the present study, the open-source CFD toolbox OpenFOAM was employed to conduct all fluid-particle dynamics simulations. Previous studies have shown that normal injection of particles through the nostrils have shown clinically insignificant amounts of olfactory deposition. The main objective of this study is to utilize the Particle Release Map (PRM) methodology to optimize the nanodrug deposition efficiency inside the olfactory region, using a representative human nasal cavity as a test bed. While published results indicate maximum olfactory depositions of 3 to 4% (for 1 nm particles) under normal breathing rate, the PRM approach achieves 28.4% deposition for 10 nm and 8.7% for 100 nm particles in the olfactory bulb. Practically, such elevated olfactory depositions with the PRM technique could be achieved in conjunction with a well-placed nasal cannula. Copyright © 2021 American Association for Aerosol Research}, journal={AEROSOL SCIENCE AND TECHNOLOGY}, author={Vachhani, Shantanu and Kleinstreuer, Clement}, year={2021}, month={Jul} } @article{kulkarni_kleinstreuer_2020, title={High-temperature effects on the mucus layers in a realistic human upper airway model}, volume={163}, ISSN={["1879-2189"]}, DOI={10.1016/j.ijheatmasstransfer.2020.120467}, abstractNote={Firefighters and workers in some industries often inhale (polluted) air at high temperatures, eg, 50–200°C, and very low relative humidity, say, 5–10%. Such severe environmental conditions may cause health problems or further aggravate existing ones. As in vivo tests are very complex, potentially harmful and costly, and in vitro experiments often lack high resolution and predictive capability, in silico studies become a priority. They may include computer simulations of the air-particle dynamics in human lung-airway models to understand the convection heat transfer as well as pollutant transport, deposition and uptake at high inlet temperatures and low relative humidity. In this study, detailed modeling, simulation and analysis focuses on two-phase flow in a human upper lung-airway model with a realistic 3D mucus lining. Especially modeling of the upper airway mucus layers was of interest in order to simulate the vapor mass transfer to the airflow because of its primary function for airway humidification. Naturally, the humidification causes water loss in the mucus layer, which leads to its reduction or even depletion when exposed to relatively high temperatures. Accounting for the changes in thickness and the rise in temperature in the mucus layer allows for the determination of locations of thermal injury in the human airways due to continuous exposure of such abnormal inhalation conditions. Different temperature profiles and local changes in mucus layer thickness were studied for ranges of severe inlet temperature conditions at a representative flow rate of 20 LPM (liters per minute). For inlet temperature reaching 100°C, mucus-layer thinning was observed in the upper airways. Interestingly, as a confirmation of the Reynolds analogy, the areas of significant wall heat flux and associated wall shear stress coincided with the regions of highest mucus evaporation, resulting in the humidification of the air with low relative humidity. Model development and mucus layer generation were done using C++ programming. All computer simulations were carried out using the open-source computational fluid dynamics toolbox OpenFOAM.}, journal={INTERNATIONAL JOURNAL OF HEAT AND MASS TRANSFER}, author={Kulkarni, Nilay Atul and Kleinstreuer, Clement}, year={2020}, month={Dec} } @article{saini_kleinstreuer_2019, title={A new collision model for ellipsoidal particles in shear flow}, volume={376}, ISSN={["1090-2716"]}, DOI={10.1016/j.jcp.2018.09.039}, abstractNote={Abstract All natural and a growing number of manufactured solid particles are non-spherical. Interesting fluid–particle dynamics applications include the transport of granular material, piling of seeds or grains, inhalation of toxic aerosols, use of nanofluids for enhanced cooling or improved lubrication, and optimal drug-targeting of tumors. A popular approach for computer simulations of such scenarios is the multi-sphere (MS) method, where any non-spherical particle is represented by an assemblage of spheres. However, the MS approach may lead to multiple sphere-to-sphere contact points during collision, and subsequently to erroneous particle transport and deposition. In cases where non-spherical particles can be approximated as ellipsoids with arbitrary aspect ratios, a new theory for particle transport, collision and wall interaction is presented which is more accurate computationally and more efficient than the MS method. In general, with the new ellipsoidal particle interaction (EPI) model, contact points and planes of ellipsoids, rather than spheres, are obtained based on a geometric potential algorithm. Then, interaction forces and torques of the colliding particles are determined via inscribed ‘pseudo-spheres’, employing the soft-particle approach. The off-center forces and moments are then transferred to the mass center of the ellipsoids to solve the appropriate translatory and angular equations of motion. Considering ellipses to illustrate the workings and predictive power of the new collision model, turbulent fluid–particle flow with the EPI model in a 2-D channel is simulated and compared with 3-D numerical benchmark results which relied on the MS method. The 2-D concentrations of micron particles with different aspect ratios matched closely with the 3-D cases. However, interesting differences occurred when comparing the particle-velocity profiles for which the 2-D EPI model generated somewhat larger particle velocities due to out-of-plane collisions, slightly higher particle–wall interactions, and two-way coupling effects.}, journal={JOURNAL OF COMPUTATIONAL PHYSICS}, author={Saini, N. and Kleinstreuer, C.}, year={2019}, month={Jan}, pages={1028–1050} } @article{xu_kleinstreuer_2019, title={Heterogeneous blood flow in microvessels with applications to nanodrug transport and mass transfer into tumor tissue}, volume={18}, ISSN={["1617-7940"]}, DOI={10.1007/s10237-018-1071-2}, abstractNote={Nanodrug transport in tumor microvasculature and deposition/extravasation into tumor tissue are an important link in the nanodrug delivery process. Considering heterogeneous blood flow, such a dual process is numerically studied. The hematocrit distribution is solved by directly considering the forces experienced by the red blood cells (RBCs), i.e., the wall lift force and the random cell collision force. Using a straight microvessel as a test bed, validated computer simulations are performed to determine blood flow characteristics as well as the resulting nanodrug distribution and extravasation. The results confirm that RBCs migrate away from the vessel wall, leaving a cell-free layer (CFL). Nanodrug particles tend to preferentially accumulate in the CFL, leading to increased concentration near the endothelial surface layer. However, shear-induced NP diffusion is diminished within the CFL, causing to a much slower lateral transport rate into tumor tissue. These competing effects determine the NP deposition/extravasation rates. The present modeling framework and NP flux results provide new physical insight. The analysis can be readily extended to simulations of NP transport in blood microvessels of actual tumors.}, number={1}, journal={BIOMECHANICS AND MODELING IN MECHANOBIOLOGY}, author={Xu, Z. and Kleinstreuer, C.}, year={2019}, month={Feb}, pages={99–110} } @article{kolanjiyil_kleinstreuer_kleinstreuer_pham_sadikot_2019, title={Mice-to-men comparison of inhaled drug-aerosol deposition and clearance}, volume={260}, ISSN={["1878-1519"]}, DOI={10.1016/j.resp.2018.11.003}, abstractNote={Part of the effective prediction of the pharmacokinetics of drugs (or toxic particles) requires extrapolation of experimental data sets from animal studies to humans. As the respiratory tracts of rodents and humans are anatomically very different, there is a need to study airflow and drug-aerosol deposition patterns in lung airways of these laboratory animals and compare them to those of human lungs. As a first step, interspecies computational comparison modeling of inhaled nano-to-micron size drugs (50 nm < d< 15μm) was performed using mouse and human upper airway models under realistic breathing conditions. Critical species-specific differences in lung physiology of the upper airways and subsequently in local drug deposition were simulated and analyzed. In addition, a hybrid modeling methodology, combining Computational Fluid-Particle Dynamics (CF-PD) simulations with deterministic lung deposition models, was developed and predicted total and regional drug-aerosol depositions in lung airways of both mouse and man were compared, accounting for the geometric, kinematic and dynamic differences. Interestingly, our results indicate that the total particle deposition fractions, especially for submicron particles, are comparable in rodent and human respiratory models for corresponding breathing conditions. However, care must be taken when extrapolating a given dosage as considerable differences were noted in the regional particle deposition pattern. Combined with the deposition model, the particle retention and clearance kinetics of deposited nanoparticles indicates that the clearance rate from the mouse lung is higher than that in the human lung. In summary, the presented computer simulation models provide detailed fluid-particle dynamics results for upper lung airways of representative human and mouse models with a comparative analysis of particle lung deposition data, including a novel mice-to-men correlation as well as a particle-clearance analysis both useful for pharmacokinetic and toxicokinetic studies.}, journal={RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY}, author={Kolanjiyil, Arun V. and Kleinstreuer, Clement and Kleinstreuer, Nicole C. and Pham, Wellington and Sadikot, Ruxana T.}, year={2019}, month={Feb}, pages={82–94} } @article{kolanjiyil_kleinstreuer_2019, title={Modeling Airflow and Particle Deposition in a Human Acinar Region}, volume={2019}, ISSN={["1748-6718"]}, DOI={10.1155/2019/5952941}, abstractNote={The alveolar region, encompassing millions of alveoli, is the most vital part of the lung. However, airflow behavior and particle deposition in that region are not fully understood because of the complex geometrical structure and intricate wall movement. Although recent investigations using 3D computer simulations have provided some valuable information, a realistic analysis of the air-particle dynamics in the acinar region is still lacking. So, to gain better physical insight, a physiologically inspired whole acinar model has been developed. Specifically, air sacs (i.e., alveoli) were attached as partial spheroids to the bifurcating airway ducts, while breathing-related wall deformation was included to simulate actual alveolar expansion and contraction. Current model predictions confirm previous notions that the location of the alveoli greatly influences the alveolar flow pattern, with recirculating flow dominant in the proximal lung region. In the midalveolar lung generations, the intensity of the recirculating flow inside alveoli decreases while radial flow increases. In the distal alveolar region, the flow pattern is completely radial. The micron/submicron particle simulation results, employing the Euler–Lagrange modeling approach, indicate that deposition depends on the inhalation conditions and particle size. Specifically, the particle deposition rate in the alveolar region increases with higher inhalation tidal volume and particle diameter. Compared to previous acinar models, the present system takes into account the entire acinar region, including both partially alveolated respiratory bronchioles as well the fully alveolated distal airways and alveolar sacs. In addition, the alveolar expansion and contraction have been calculated based on physiological breathing conditions which make it easy to compare and validate model results with in vivo lung deposition measurements. Thus, the current work can be readily incorporated into human whole-lung airway models to simulate/predict the flow dynamics of toxic or therapeutic aerosols.}, journal={COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE}, author={Kolanjiyil, Arun V. and Kleinstreuer, Clement}, year={2019} } @misc{mahian_kolsi_amani_estelle_ahmadi_kleinstreuer_marshalli_siavashi_taylor_niazmand_et al._2019, title={Recent advances in modeling and simulation of nanofluid flows-Part I: Fundamentals and theory}, volume={790}, ISSN={["1873-6270"]}, DOI={10.1016/j.physrep.2018.11.004}, abstractNote={It has been more than two decades since the discovery of nanofluids-mixtures of common liquids and solid nanoparticles less than 100 nm in size. As a type of colloidal suspension, nanofluids are typically employed as heat transfer fluids due to their favorable thermal and fluid properties. There have been numerous numerical studies of nanofluids in recent years (more than 1000 in both 2016 and 2017, based on Scopus statistics). Due to the small size and large numbers of nanoparticles that interact with the surrounding fluid in nanofluid flows, it has been a major challenge to capture both the macro-scale and the nano-scale effects of these systems without incurring extraordinarily high computational costs. To help understand the state of the art in modeling nanofluids and to discuss the challenges that remain in this field, the present article reviews the latest developments in modeling of nanofluid flows and heat transfer with an emphasis on 3D simulations. In part I, a brief overview of nanofluids (fabrication, applications, and their achievable thermo-physical properties) will be presented first. Next, various forces that exist in particulate flows such as drag, lift (Magnus and Saffman), Brownian, thermophoretic, van der Waals, and electrostatic double layer forces and their significance in nanofluid flows are discussed. Afterwards, the main models used to calculate the thermophysical properties of nanofluids are reviewed. This will be followed with the description of the main physical models presented for nanofluid flows and heat transfer, from single-phase to Eulerian and Lagrangian two-phase models. In part II, various computational fluid dynamics (CFD) techniques will be presented. Next, the latest studies on 3D simulation of nanofluid flow in various regimes and configurations are reviewed. The present review is expected to be helpful for researchers working on numerical simulation of nanofluids and also for scholars who work on experimental aspects of nanofluids to understand the underlying physical phenomena occurring during their experiments.}, journal={PHYSICS REPORTS-REVIEW SECTION OF PHYSICS LETTERS}, author={Mahian, Omid and Kolsi, Lioua and Amani, Mohammad and Estelle, Patrice and Ahmadi, Goodarz and Kleinstreuer, Clement and Marshalli, Jeffrey S. and Siavashi, Majid and Taylor, Robert A. and Niazmand, Hamid and et al.}, year={2019}, month={Feb}, pages={1–48} } @misc{mahian_kolsi_amani_estelle_ahmadi_kleinstreuer_marshall_taylor_abu-nada_rashidi_et al._2019, title={Recent advances in modeling and simulation of nanofluid flows-Part II: Applications}, volume={791}, ISSN={["1873-6270"]}, DOI={10.1016/j.physrep.2018.11.003}, abstractNote={Modeling and simulation of nanofluid flows is crucial for applications ranging from the cooling of electronic devices to solar water heating systems, particularly when compared to the high expense of experimental studies. Accurate simulation of a thermal-fluid system requires a deep understanding of the underlying physical phenomena occurring in the system. In the case of a complex nanofluid-based system, suitable simplifying approximations must be chosen to strike a balance between the nano-scale and macro-scale phenomena. Based on these choices, the computational approach – or set of approaches – to solve the mathematical model can be identified, implemented and validated. In Part I of this review (Mahian et al., 2019), we presented the details of various approaches that are used for modeling nanofluid flows, which can be classified into single-phase and two-phase approaches. Now, in Part II, the main computational methods for solving the transport equations associated with nanofluid flow are briefly summarized, including the finite difference, finite volume, finite element, lattice Boltzmann methods, and Lagrangian methods (such as dissipative particle dynamics and molecular dynamics). Next, the latest studies on 3D simulation of nanofluid flow in various regimes and configurations are reviewed. The numerical studies in the literature mostly focus on various forms of heat exchangers, such as solar collectors (flat plate and parabolic solar collectors), microchannels, car radiators, and blast furnace stave coolers along with a few other important nanofluid flow applications. Attention is given to the difference between 2D and 3D simulations, the effect of using different computational approaches on the flow and thermal performance predictions, and the influence of the selected physical model on the computational results. Finally, the knowledge gaps in this field are discussed in detail, along with some suggestions for the next steps in this field. The present review, prepared in two parts, is intended to be a comprehensive reference for researchers and practitioners interested in nanofluids and in the many applications of nanofluid flows.}, journal={PHYSICS REPORTS-REVIEW SECTION OF PHYSICS LETTERS}, author={Mahian, Omid and Kolsi, Lioua and Amani, Mohammad and Estelle, Patrice and Ahmadi, Goodarz and Kleinstreuer, Clement and Marshall, Jeffrey S. and Taylor, Robert A. and Abu-Nada, Eiyad and Rashidi, Saman and et al.}, year={2019}, month={Feb}, pages={1–59} } @article{feng_zhao_kleinstreuer_wang_wang_wu_lin_2018, title={An in silico inter-subject variability study of extra-thoracic morphology effects on inhaled particle transport and deposition}, volume={123}, ISSN={["1879-1964"]}, DOI={10.1016/j.jaerosci.2018.05.010}, abstractNote={An understanding of human inter-subject variability is crucial for the implementation of personalized pulmonary drug delivery as well as exposure assessment of airborne hazardous materials. However, due to the lack of statistically robust data and subsequent comparisons, the influence of human respiratory morphology on inhaled nano-/micro-particle transport and deposition is still not fully known. Thus, focusing on identifying geometric parameters that significantly influence airflow and inhaled particle transport/deposition, an experimentally validated Computational Fluid-Particle Dynamics (CFPD) model based on the Euler-Lagrange method is developed. In analyzing deposition patterns to fill the knowledge gap, the particles are grouped into six diameter groups, i.e., 0.05, 0.1, 0.5, 2, 5, and 10 µm. To enhance the statistical robustness of the investigation, a virtual population group is created that contains seven distinct and widely used human upper-airway configurations, where the same tracheobronchial trees are extended to Generation 6 (G6). Numerical results and the inter-subject variability analysis indicate that the glottis constriction is the morphological parameter that significantly impacts the inhaled particle dynamics in the respiratory tract. For reasons of statistical robustness, anatomical features of the upper airways should be maintained to capture the personalized airflow and particle transport dynamics for particles smaller than 500 nm or larger than 2 µm. However, a single upper airway model, representing a basic subpopulation group, can be employed to evaluate the total deposition of particles in the diameter range of 500 nm < dp < 2 µm. The present study provides an in silico lung-aerosol dynamics framework with detailed particle-deposition results and new physical insight. It may serve as a guide for implementing optimal targeting of inhaled drug-aerosols as well as for the assessment of hazardous aerosol exposure in distinct populations.}, journal={JOURNAL OF AEROSOL SCIENCE}, author={Feng, Yu and Zhao, Jianan and Kleinstreuer, Clement and Wang, Qingsheng and Wang, Jun and Wu, Dee H. and Lin, Jiang}, year={2018}, month={Sep}, pages={185–207} } @article{chari_kleinstreuer_2018, title={Convective mass and heat transfer enhancement of nanofluid streams in bifurcating microchannels}, volume={125}, ISSN={["1879-2189"]}, DOI={10.1016/j.ijheatmasstransfer.2018.04.075}, abstractNote={Significantly improved mixing and heat transfer between two nanofluid streams in a Y-shaped sinusoidal microchannel have been achieved via geometric modifications and changes in pulsatile flow conditions. As a result a new mass-and-heat transfer correlation has been obtained as well. The geometry modification was done in two distinct parts. First, the phase shift (ϕ) between the wavy walls of the Y-channel was varied for three different shift values 0°,90°,180°. Once the shift that yielded the highest degree of mixing was determined, the included angle (α) between the input streams was varied 30°,45°,60°. The numerical results show that α=60° and ϕ=90° yield best results. The inlet streams are pulsatile with a velocity of the form V+δVsinωt+Φ where V,δV,ω,Φ are the average velocity, pulse amplitude, pulse frequency and phase shift respectively. Flow variations have been implemented via different phase shifts 45°,90°,135°,180°, different phase amplitudes and different phase frequencies. For the sake of comparison and ease of plotting, non-dimensional parameters have been used. The frequency has been captured by the non-dimensional Strouhal number (St) and the amplitude by the amplitude ratio (δV/V). The average degree of mixing (ζ), which is observed to undergo spatial variations along the exit channel as well as temporal fluctuations over one pulsation cycle is shown to be most sensitive to the amplitude and frequency of pulsations. For a fixed amplitude, the average degree of mixing increases with elevated Strouhal numbers. It reaches a peak at a particular St value and then decreases with further increase in St. The St where the degree of mixing peaks depends on the amplitude of pulsations. For δV/V⩾5, the degree of mixing peaks at St≈0.5. For δV/V⩽5, the degree of mixing peaks at St≈2. Unlike mixing, the heat transfer rate, characterized by the non-dimensional Nusselt number (Nu) peaks at higher frequency values for all δV/V ratios. To generate higher amplitudes in the pulsating flow, a larger pumping power would be required. Hence, to minimize energy cost, low amplitude and high frequency pulsations are most suitable for optimal mixing and heat transfer. Finally, a microchannel with optimized geometry and inlet flow conditions is proposed, which takes advantage of the flow instabilities created by the modified geometry and pulsating flow to yield the highest degree of mixing and heat transfer within the listed constraints. Functional dependencies have been established, based on computer experiments, between non-dimensional parameters such as St,δV/V,ζ,Nu . As a result, a correlation between mixing and heat transfer was developed which allows studying one quantity, say, the Nusset number Nu, to readily obtain the average degree of mixing ζ.}, journal={INTERNATIONAL JOURNAL OF HEAT AND MASS TRANSFER}, author={Chari, Sriram and Kleinstreuer, Clement}, year={2018}, month={Oct}, pages={1212–1229} } @article{xu_kleinstreuer_2018, title={Direct nanodrug delivery for tumor targeting subject to shear-augmented diffusion in blood flow}, volume={56}, ISSN={["1741-0444"]}, DOI={10.1007/s11517-018-1818-z}, abstractNote={The advent of multifunctional nanoparticle has enabled numerous innovative strategies in diagnostics, imaging, and cancer therapy. Despite the intense research efforts in developing new nanoparticles and surface bonding ligands, one major obstacle in achieving highly effective treatment, including minimizing detrimental side effects, is the inability to deliver drug-carrying nanoparticles from the injection point directly to the tumor site. The present study seeks to employ a direct nanodrug delivery methodology to feed multifunctional nanoparticles directly to tumor vasculatures, sparing healthy tissue. An important aspect to examine is how the interactions between such nanoparticles and relatively large red blood cells would affect the transport and delivery efficiency of nanodrugs. So, a novel computer simulation model has been developed to study nanoparticle transport in a representative human hepatic artery system, subject to shear-induced diffusion of nanoparticles due to hydrodynamic interactions with red blood cells. The particle-size effect was also evaluated by comparing the dynamics of nanoparticles with microspheres. Results from computer simulations under physiologically realistic conditions indicate that shear-induced diffusion has a significant effect on nanoparticle transport, even in large arteries. Nevertheless, as documented, direct nanodrug delivery to tumor-feeding hepatic artery branches is feasible. Graphical abstract Direct nanodrug delivery from injection point to tumor-feeding artery branch.}, number={11}, journal={MEDICAL & BIOLOGICAL ENGINEERING & COMPUTING}, author={Xu, Zelin and Kleinstreuer, Clement}, year={2018}, month={Nov}, pages={1949–1958} } @article{chen_kleinstreuer_zhong_feng_zhou_2018, title={Effects of thermal airflow and mucus-layer interaction on hygroscopic droplet deposition in a simple mouth–throat model}, volume={52}, ISSN={0278-6826 1521-7388}, url={http://dx.doi.org/10.1080/02786826.2018.1476751}, DOI={10.1080/02786826.2018.1476751}, abstractNote={Abstract Hygroscopic growth of inhaled aerosols plays an important role in determining particle trajectories and hence local deposition sites. Accurate predictions of airway temperature and humidity as well as droplet–vapor interaction are critical for the calculation of hygroscopic growth. Employing a simple mouth–throat (MT) model as a computer simulation test bed, the effects of interactive heat transfer between air–droplet flow and mucus-tissue-layer have been analyzed. For a steady inhalation flow rate of 15 L/min, air temperature and relative humidity distributions affecting droplet growth, deposition efficiency (DE), and deposition pattern have been compared for different thermal airway-wall conditions. The effects considered include: (i) the latent heat of mucus-layer evaporation and convection heat transfer; (ii) convection heat transfer only; and (iii) mucus-tissue layer with constant temperature. As the most important outcome, the validated modeling results show that thermal airflow and mucus-layer interaction can significantly reduce hygroscopic growth and thereby decrease the DE of multicomponent droplets up to 10%. The modeling framework presented can be readily expanded to other systems. Copyright © 2018 American Association for Aerosol Research}, number={8}, journal={Aerosol Science and Technology}, publisher={Informa UK Limited}, author={Chen, Xiaole and Kleinstreuer, Clement and Zhong, Wenqi and Feng, Yu and Zhou, Xianguang}, year={2018}, month={Jul}, pages={900–912} } @book{clement_2018, place={Boca Raton, Florida}, title={Modern Fluid Dynamics}, ISBN={9781315226279}, url={http://dx.doi.org/10.1201/b22066}, DOI={10.1201/b22066}, abstractNote={Modern Fluid Dynamics, Second Edition provides up-to-date coverage of intermediate and advanced fluids topics. The text emphasizes fundamentals and applications, supported by worked examples and case studies. Scale analysis, non-Newtonian fluid flow, surface coating, convection heat transfer, lubrication, fluid-particle dynamics, microfluidics, entropy generation, and fluid-structure interactions are among the topics covered. Part A presents fluids principles, and prepares readers for the applications of fluid dynamics covered in Part B, which includes computer simulations and project writing. A review of the engineering math needed for fluid dynamics is included in an appendix.}, publisher={CRC Press}, author={Clement, Kleinstreuer}, year={2018}, month={Apr} } @article{calmet_kleinstreuer_houzeaux_kolanjiyil_lehmkuhl_olivares_vazquez_2018, title={Subject-variability effects on micron particle deposition in human nasal cavities}, volume={115}, ISSN={["1879-1964"]}, DOI={10.1016/j.jaerosci.2017.10.008}, abstractNote={Validated computer simulations of the airflow and particle dynamics in human nasal cavities are important for local, segmental and total deposition predictions of both inhaled toxic and therapeutic particles. Considering three, quite different subject-specific nasal airway configurations, micron-particle transport and deposition for low-to-medium flow rates have been analyzed. Of special interest was the olfactory region from which deposited drugs could readily migrate to the central nervous system for effective treatment. A secondary objective was the development of a new dimensionless group with which total particle deposition efficiency curves are very similar for all airway models, i.e., greatly reducing the impact of intersubject variability. Assuming dilute particle suspensions with inhalation flow rates ranging from 7.5 to 20 L/min, the airflow and particle-trajectory equations were solved in parallel with the in-house, multi-purpose Alya program at the Barcelona Supercomputing Center. The geometrically complex nasal airways generated intriguing airflow fields where the three subject models exhibit among them both similar as well as diverse flow structures and wall shear stress distributions, all related to the coupled particle transport and deposition. Nevertheless, with the new Stokes-Reynolds-number group, Stk1.23Re1.28, the total deposition-efficiency curves for all three subjects and flow rates almost collapsed to a single function. However, local particle deposition efficiencies differed significantly for the three subjects when using particle diameters dp = 2, 10, and 20μm. Only one of the three subject-specific olfactory regions received, at relatively high values of the inertial parameter dp2Q, some inhaled microspheres. Clearly, for drug delivery to the brain via the olfactory region, a new method of directional inhalation of nanoparticles would have to be implemented.}, journal={JOURNAL OF AEROSOL SCIENCE}, author={Calmet, H. and Kleinstreuer, C. and Houzeaux, G. and Kolanjiyil, A. V. and Lehmkuhl, O. and Olivares, E. and Vazquez, M.}, year={2018}, month={Jan}, pages={12–28} } @article{kolanjiyil_kleinstreuer_2017, title={Computational analysis of aerosol-dynamics in a human whole-lung airway model}, volume={114}, ISSN={["1879-1964"]}, DOI={10.1016/j.jaerosci.2017.10.001}, abstractNote={Prediction of the air-particle dynamics in human lungs can reveal critical deposition sites of toxins or can determine best physical parameters for direct drug delivery and associated inhaler devices. However, the sheer complexity of the human lung, featuring a total of 16 million airways, prohibits a full-scale study. So, as an alternative, a physiologically realistic and computationally efficient computer simulation model has been developed. The configuration of the new whole-lung airway model (WLAM) consists of subject-specific upper airways from nose/mouth to, say, generation 3, which are then connected to adjustable triple bifurcation units (TBUs). These TBUs are in series and parallel to cover the remaining generations, based on morphometric measurements of human lung casts. Actual transient airflow, fluid-particle dynamics and alveolar tissue dynamics have been implemented to evaluate the impact of all respiratory airways under realistic inlet conditions. Specifically, the expanding and contracting motion of the alveoli mimic inhalation and exhalation in the alveolar region. Particle transport and deposition depend on the lung-airway geometry, particle characteristics, and inhalation flow frequency. Considering inhalation/exhalation in form of a square-wave breathing profile at 15 L/min with different tidal volumes and 3 μm-size microspheres as a WLAM test case, significantly higher deposition was observed in the alveolar region than in the upper airways. For short and light breathing conditions, multiple breathing cycles are required to exhale all the suspended particles. Particle deposition patterns differ for inhalation vs. exhalation, as well as in subsequent breathing cycles. During later cycles, the suspended particles tend to travel to distal airways. The model predictions agree well with in vivo results. The new WLAM can be used for local, segmental and total deposition predictions of inhaled toxic or therapeutic aerosols, and for providing inhaler-design guidelines to improve drug-aerosol targeting.}, journal={JOURNAL OF AEROSOL SCIENCE}, author={Kolanjiyil, Arun V. and Kleinstreuer, Clement}, year={2017}, month={Dec}, pages={301–316} } @article{kolanjiyil_kleinstreuer_sadikot_2017, title={Computationally efficient analysis of particle transport and deposition in a human whole-lung-airway model. Part II: Dry powder inhaler application}, volume={84}, ISSN={0010-4825}, url={http://dx.doi.org/10.1016/J.COMPBIOMED.2016.10.025}, DOI={10.1016/J.COMPBIOMED.2016.10.025}, abstractNote={Pulmonary drug delivery is becoming a favored route for administering drugs to treat both lung and systemic diseases. Examples of lung diseases include asthma, cystic fibrosis and chronic obstructive pulmonary disease (COPD) as well as respiratory distress syndrome (ARDS) and pulmonary fibrosis. Special respiratory drugs are administered to the lungs, using an appropriate inhaler device. Next to the pressurized metered-dose inhaler (pMDI), the dry powder inhaler (DPI) is a frequently used device because of the good drug stability and a minimal need for patient coordination. Specific DPI-designs and operations greatly affect drug-aerosol formation and hence local lung deposition. Simulating the fluid-particle dynamics after use of a DPI allows for the assessment of drug-aerosol deposition and can also assist in improving the device configuration and operation. In Part I of this study a first-generation whole lung-airway model (WLAM) was introduced and discussed to analyze particle transport and deposition in a human respiratory tract model. In the present Part II the drug-aerosols are assumed to be injected into the lung airways from a DPI mouth-piece, forming the mouth-inlet. The total as well as regional particle depositions in the WLAM, as inhaled from a DPI, were successfully compared with experimental data sets reported in the open literature. The validated modeling methodology was then employed to study the delivery of curcumin aerosols into lung airways using a commercial DPI. Curcumin has been implicated to possess high therapeutic potential as an antioxidant, anti-inflammatory and anti-cancer agent. However, efficacy of curcumin treatment is limited because of the low bioavailability of curcumin when ingested. Hence, alternative drug administration techniques, e.g., using inhalable curcumin-aerosols, are under investigation. Based on the present results, it can be concluded that use of a DPI leads to low lung deposition efficiencies because large amounts of drugs are deposited in the oral cavity. Hence, the output of a modified DPI has been evaluated to achieve improved drug delivery, especially needed when targeting the smaller lung airways. This study is the first to utilize CF-PD methodology to simulate drug-aerosol transport and deposition under actual breathing conditions in a whole lung model, using a commercial dry-powder inhaler for realistic inlet conditions.}, journal={Computers in Biology and Medicine}, publisher={Elsevier BV}, author={Kolanjiyil, Arun V. and Kleinstreuer, Clement and Sadikot, Ruxana T.}, year={2017}, month={May}, pages={247–253} } @article{chen_feng_zhong_kleinstreuer_2017, title={Numerical investigation of the interaction, transport and deposition of multicomponent droplets in a simple mouth-throat model}, volume={105}, ISSN={["1879-1964"]}, DOI={10.1016/j.jaerosci.2016.12.001}, abstractNote={A basic analysis of inhaled multicomponent droplet-vapor interaction and subsequent aerosol deposition is very important for the understanding of natural phenomena as well as for health-care related applications. Employing a highly idealized mouth-throat (MT) model as a test bed, the transport and deposition mechanisms of a water-droplet are simulated, considering ethanol, sodium chloride and fluorescein as components. The flow-field equations are solved with a validated transition SST model which can predict the effects of flow rate, relative humidity (RH), and wet vs. dry airway walls on aerosol deposition efficiency (DE). The simulation results indicate that the hygroscopic growth of sodium chloride particles is sensitive to the saturation pressure of water vapor. A high flow rate decreases the RH in the airways as well as the average growth ratios of deposited and escaped droplets; but, still increases the DE. When compared to a dry boundary condition, the wet airway-wall increases the DE up to 4.6% when RH=30% and the flow rate is 60 L/min. It also increases the average growth ratio of deposited droplets notably, i.e., larger than 0.5 for most conditions, while its effect on the average growth ratio of deposited droplets is not apparent. A high inlet RH can significantly enhance the hygroscopic growth of the droplets and DE, especially when it is larger than the RH threshold for the hygroscopic component. Besides, it can elevate the growth ratios of deposited and escaped droplets at the same time, which could be utilized to reduce the deposition of submicron hygroscopic aerosol in the upper airway.}, journal={JOURNAL OF AEROSOL SCIENCE}, author={Chen, Xiaole and Feng, Yu and Zhong, Wenqi and Kleinstreuer, Clement}, year={2017}, month={Mar}, pages={108–127} } @article{feng_kleinstreuer_castro_rostami_2016, title={Computational transport, phase change and deposition analysis of inhaled multicomponent droplet-vapor mixtures in an idealized human upper lung model}, volume={96}, ISSN={["1879-1964"]}, DOI={10.1016/j.jaerosci.2016.03.001}, abstractNote={Numerous inhalable aerosols consist of multiple nano-to-microscale solid or liquid particles with dissolved or embedded compounds, as well as associated vapors. In general, of interest are the transport and conversion phenomena leading to local particle/droplet/vapor depositions. Selected examples include inhalation of aerosols from use of inhalers, cigarettes and electronic cigarettes. In this study the focus is on hygroscopic growth of nano-size multi-component droplets and droplet–vapor interactions during transport with subsequent deposition in a human upper lung-airway model. For that purpose a comprehensive and efficient computational fluid–particle dynamics model has been developed. It is capable of simultaneously analyzing multi-component droplet–vapor and airflow interactions with evaporation and condensation effects for different sets of inhalation conditions. Selecting inhaled electronic cigarette (EC) aerosols as an application, the simulation results include detailed transport, deposition and absorption data for different constituents (i.e., water, propylene glycol, glycerol and nicotine) in both vapor and liquid forms for an idealized human upper lung airway geometry, i.e., from mouth to generation 3. Results indicate that liquid–vapor phase change induces hygroscopic growth of droplets, which in turn impacts significantly the deposition concentrations of aerosols via inertial impaction, secondary flows, Brownian motion, and the vapor-specific absorption rates. Parametric sensitivity analyses were performed to evaluate the influence of different inhalation flow waveforms on EC-aerosol transport, interaction, and deposition.}, journal={JOURNAL OF AEROSOL SCIENCE}, author={Feng, Yu and Kleinstreuer, Clement and Castro, Nicolas and Rostami, Ali}, year={2016}, month={Jun}, pages={96–123} } @article{kolanjiyil_kleinstreuer_2016, title={Computationally efficient analysis of particle transport and deposition in a human whole-lung-airway model. Part I: Theory and model validation}, volume={79}, ISSN={["1879-0534"]}, DOI={10.1016/j.compbiomed.2016.10.020}, abstractNote={Computational predictions of aerosol transport and deposition in the human respiratory tract can assist in evaluating detrimental or therapeutic health effects when inhaling toxic particles or administering drugs. However, the sheer complexity of the human lung, featuring a total of 16 million tubular airways, prohibits detailed computer simulations of the fluid-particle dynamics for the entire respiratory system. Thus, in order to obtain useful and efficient particle deposition results, an alternative modeling approach is necessary where the whole-lung geometry is approximated and physiological boundary conditions are implemented to simulate breathing. In Part I, the present new whole-lung-airway model (WLAM) represents the actual lung geometry via a basic 3-D mouth-to-trachea configuration while all subsequent airways are lumped together, i.e., reduced to an exponentially expanding 1-D conduit. The diameter for each generation of the 1-D extension can be obtained on a subject-specific basis from the calculated total volume which represents each generation of the individual. The alveolar volume was added based on the approximate number of alveoli per generation. A wall-displacement boundary condition was applied at the bottom surface of the first-generation WLAM, so that any breathing pattern due to the negative alveolar pressure can be reproduced. Specifically, different inhalation/exhalation scenarios (rest, exercise, etc.) were implemented by controlling the wall/mesh displacements to simulate realistic breathing cycles in the WLAM. Total and regional particle deposition results agree with experimental lung deposition results. The outcomes provide critical insight to and quantitative results of aerosol deposition in human whole-lung airways with modest computational resources. Hence, the WLAM can be used in analyzing human exposure to toxic particulate matter or it can assist in estimating pharmacological effects of administered drug-aerosols. As a practical WLAM application, the transport and deposition of asthma drugs from a commercial dry-powder inhaler is discussed in Part II.}, journal={COMPUTERS IN BIOLOGY AND MEDICINE}, author={Kolanjiyil, Arun V. and Kleinstreuer, Clement}, year={2016}, month={Dec}, pages={193–204} } @article{chen_zhong_tom_kleinstreuer_feng_he_2016, title={Experimental-computational study of fibrous particle transport and deposition in a bifurcating lung model}, volume={28}, ISSN={["2210-4291"]}, DOI={10.1016/j.partic.2016.02.002}, abstractNote={Experiments carried out using a lung model with a single horizontal bifurcation under different steady inhalation conditions explored the orientation of depositing carbon fibers, and particle deposition fractions. The orientations of deposited fibers were obtained from micrographs. Specifically, the effects of the sedimentation parameter (γ), fiber length, and flow rate on orientations were analyzed. Our results indicate that gravitational effect on deposition cannot be neglected for 0.0228 < γ < 0.247. The absolute orientation angle of depositing fibers decreased linearly with increasing γ for values 0.0228 < γ < 0.15. Correspondence between Stokes numbers and γ suggests these characteristics can be used to estimate fiber deposition in the lower airways. Computer simulations with sphere-equivalent diameter models for the fibers explored deposition efficiency vs. Stokes number. Using the volume-equivalent diameter model, our experimental data for the horizontal bifurcation were replicated. Results for particle deposition using a lung model with a vertical bifurcation indicate that body position also affects deposition.}, journal={PARTICUOLOGY}, author={Chen, Xiaole and Zhong, Wenqi and Tom, Josin and Kleinstreuer, Clement and Feng, Yu and He, Xiaopu}, year={2016}, month={Aug}, pages={102–113} } @article{vaish_kleinstreuer_kolanjiyil_saini_pillalamarri_2016, title={Laminar/turbulent airflow and microsphere deposition in a patient-specific airway geometry using an open-source solver}, volume={22}, ISSN={["1752-6426"]}, DOI={10.1504/ijbet.2016.079145}, abstractNote={Using the open-source software OpenFOAM as the solver, airflow and microsphere transport have been simulated in a patient-specific lung-airway model. A suitable transitional turbulence model was validated and implemented to accurately simulate airflow fields, as the laryngeal jet occurring in the throat region may induce turbulence immediately downstream. Furthermore, a modified eddy interaction model with a generalised near-wall correction factor is presented that more accurately simulates the particle trajectories and subsequent deposition phenomena which are especially affected by near-wall velocity fluctuations. Particle depositions in the realistic lung-airway configuration are compared with those in an idealised upper airway model. The results indicate that for microsphere deposition in turbulent airflow regions, selection of an appropriate near-wall correction factor can reduce the problem of subject variability for different lung-airway configurations. Open-source solvers for lung-aerosol dynamics simulations, such as OpenFOAM, are predictive tools which are basically cost-free, flexible, largely user-friendly, and portable.}, number={2}, journal={INTERNATIONAL JOURNAL OF BIOMEDICAL ENGINEERING AND TECHNOLOGY}, author={Vaish, Mayank and Kleinstreuer, Clement and Kolanjiyil, Arun V. and Saini, Nadish and Pillalamarri, Narasimha R.}, year={2016}, pages={145–161} } @article{xu_jernigan_kleinstreuer_buckner_2016, title={Solid Tumor Embolotherapy in Hepatic Arteries with an Anti-reflux Catheter System}, volume={44}, ISSN={["1573-9686"]}, DOI={10.1007/s10439-015-1411-7}, abstractNote={Unresectable hepatoma accounts for the majority of malignant liver tumor cases for which embolization therapy is considered a viable treatment option. However, the potential risk of aberrant particle deposition in non-target regions could cause severe side-effects, alongside diminished efficacy. A computational model has been developed to analyze the particle-hemodynamics before and after deployment of an FDA-approved anti-reflux catheter. The catheter features a retractable, porous cone-like tip designed to allow forward blood flow while preventing microsphere reflux. A patient-specific hepatic artery system, with different daughter branches connected to a liver tumor, was chosen as a representative test bed. In vitro as well as in vivo measurements were used to validate the computer simulation model. The model captures the effect of tip-deployment on blood perfusion and pressure drop in an interactive manner under physiologically realistic conditions. A relationship between the pressure drop and embolization level was established, which can be used to provide clinicians with real-time information on the best infusion-stop point. However, the results show that the present procedure for embolization of downstream vessels which feed a tumor is quite arbitrary. Nevertheless, a method to recycle aberrant particles captured by the deployed tip was proposed to minimize side-effects.}, number={4}, journal={ANNALS OF BIOMEDICAL ENGINEERING}, author={Xu, Zelin and Jernigan, Shaphan and Kleinstreuer, Clement and Buckner, Gregory D.}, year={2016}, month={Apr}, pages={1036–1046} } @article{vaish_kleinstreuer_2015, title={A Lagrangian Approach for Calculating Microsphere Deposition in a One-Dimensional Lung-Airway Model}, volume={137}, ISSN={["1528-8951"]}, DOI={10.1115/1.4030977}, abstractNote={Using the open-source software openfoam as the solver, a novel approach to calculate microsphere transport and deposition in a 1D human lung-equivalent trumpet model (TM) is presented. Specifically, for particle deposition in a nonlinear trumpetlike configuration a new radial force has been developed which, along with the regular drag force, generates particle trajectories toward the wall. The new semi-empirical force is a function of any given inlet volumetric flow rate, micron-particle diameter, and lung volume. Particle-deposition fractions (DFs) in the size range from 2 μm to 10 μm are in agreement with experimental datasets for different laminar and turbulent inhalation flow rates as well as total volumes. Typical run times on a single processor workstation to obtain actual total deposition results at comparable accuracy are 200 times less than that for an idealized whole-lung geometry (i.e., a 3D–1D model with airways up to 23rd generation in single-path only).}, number={9}, journal={JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME}, author={Vaish, Mayank and Kleinstreuer, Clement}, year={2015}, month={Sep} } @article{umbarkar_kleinstreuer_2015, title={Computationally Efficient Fluid-Particle Dynamics Simulations of Arterial Systems}, volume={17}, ISSN={["1991-7120"]}, DOI={10.4208/cicp.160114.120914a}, abstractNote={Abstract}, number={2}, journal={COMMUNICATIONS IN COMPUTATIONAL PHYSICS}, author={Umbarkar, Tejas S. and Kleinstreuer, Clement}, year={2015}, month={Feb}, pages={401–423} } @article{feng_kleinstreuer_rostami_2015, title={Evaporation and condensation of multicomponent electronic cigarette droplets and conventional cigarette smoke particles in an idealized G3-G6 triple bifurcating unit}, volume={80}, ISSN={["1879-1964"]}, DOI={10.1016/j.jaerosci.2014.11.002}, abstractNote={The present research study is intended to provide fundamental understanding of the dynamics and transport of aerosols from an e-cigarette in an idealized tubular G3–G6 respiratory tract model. A computational model has been developed that includes the effects of hygroscopic growth as well as evaporation from multicomponent aerosol droplets. The aerosols investigated usually contain carrier solvents such as propylene glycol (PG) and glycerol, along with water, nicotine, and flavors. An experimentally validated computational fluid-particle dynamics (CF-PD) model is presented, which for the first time is capable of simultaneously simulating interactive, multicomponent droplet-vapor dynamics with evaporation and/or condensation. As a first step to accomplish such complex numerical simulations, an idealized G3–G6 triple bifurcating unit (TBU) has been selected. The results are compared with the conventional smoke particles (CSPs) as well as solid particles. Parametric analysis and comparisons of the evaporation/condensation dynamics for EC-droplets vs. cigarette smoke particles were performed, including the effects of different droplet initial diameter, composition, temperature, and ambient relative humidity. The results indicate that EC-droplets, being more hygroscopic than cigarette smoke particles, tend to grow larger in maximum size in a typically highly humid environment. Additionally, a correlation for the growth ratio of EC-droplets in TBUs is proposed.}, journal={JOURNAL OF AEROSOL SCIENCE}, author={Feng, Y. and Kleinstreuer, C. and Rostami, A.}, year={2015}, month={Feb}, pages={58–74} } @article{childress_kleinstreuer_2014, title={Computationally Efficient Particle Release Map Determination for Direct Tumor-Targeting in a Representative Hepatic Artery System}, volume={136}, ISSN={["1528-8951"]}, DOI={10.1115/1.4025881}, abstractNote={Implementation of a novel direct tumor-targeting technique requires a computer modeling stage to generate particle release maps (PRMs) which allow for optimal catheter positioning and selection of best injection intervals for drug-particles. This simulation task for a patient-specific PRM may require excessive computational resources and a relatively long turn-around time for a fully transient analysis. Hence, steady-state conditions were sought which generates PRMs equivalent to the pulsatile arterial flow environment. Fluid-particle transport in a representative hepatic artery system was simulated under fully transient and steady-state flow conditions and their corresponding PRMs were analyzed and compared. Comparisons of the transient PRMs from ten equal intervals of the cardiac pulse revealed that the diastolic phase produced relatively constant PRMs due to its semisteady flow conditions. Furthermore, steady-state PRMs, which best matched the transient particle release maps, were found for each interval and over the entire cardiac pulse. From these comparisons, the flow rate and outlet pressure differences proved to be important parameters for estimating the PRMs. The computational times of the fully transient and steady simulations differed greatly, i.e., about 10 days versus 0.5 to 1 h, respectively. The time-averaged scenario may provide the best steady conditions for estimating the transient particle release maps. However, given the considerable changes in the PRMs due to the accelerating and decelerating phases of the cardiac cycle, it may be better to model several steady scenarios, which encompass the wide range of flows and pressures experienced by the arterial system in order to observe how the PRMs may change throughout the pulse. While adding more computation time, this method is still significantly faster than running the full transient case. Finally, while the best steady PRMs provide a qualitative guide for best catheter placement, the final injection position could be adjusted in vivo using biodegradable mock-spheres to ensure that patient-specific optimal tumor-targeting is achieved. In general, the methodology described could generate computationally very efficient and sufficiently accurate solutions for the transient fluid-particle dynamics problem. However, future work should test this methodology in patient-specific geometries subject to various flow waveforms.}, number={1}, journal={JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME}, author={Childress, E. M. and Kleinstreuer, C.}, year={2014}, month={Jan} } @article{xu_kleinstreuer_2014, title={Concentration photovoltaic-thermal energy co-generation system using nanofluids for cooling and heating}, volume={87}, ISSN={["1879-2227"]}, DOI={10.1016/j.enconman.2014.07.047}, abstractNote={New designs of dual concentration photovoltaic–thermal (CPV/T) systems can provide both electrical and thermal energy, while reducing solar cell material usage via optical techniques. The overall system efficiency can be improved by using advanced dual-purpose liquids with enhanced heat transfer characteristics, such as nanofluids. In this paper the use of nanofluids, i.e., dilute nanoparticle suspensions in liquids, are considered for improved efficiency of a CPV/T system for the first time. Specifically, a 2-D model coupling thermal analysis and computational fluid dynamics simulations has been developed to calculate efficiencies of individual subsystems as well as the overall system. A new thermal conductivity model for nanofluids, which was validated with experimental data sets, was employed. The electrical and thermal performances of the system were evaluated for different climatic conditions. The results show that using nanofluids improves the electrical and total efficiencies of the system, especially when using silicon solar cells. For example, if the nanofluid outlet temperature of the solar cell is set to 62 °C via a controlled flow rate, the system overall efficiency could reach 70% with electrical and thermal contributions amounting to 11% and 59%, respectively. In summary, a nanofluid-based system is preferable to water-based systems in the long run.}, journal={ENERGY CONVERSION AND MANAGEMENT}, author={Xu, Zelin and Kleinstreuer, Clement}, year={2014}, month={Nov}, pages={504–512} } @inproceedings{feng_kleinstreuer_2014, title={DDPM-DEM simulations of particulate flows in human tracheobronchial airways}, DOI={10.1115/imece2013-62307}, abstractNote={Dense particle-suspension flows in which particle-particle interactions are a dominant feature encompass a diverse range of industrial and geophysical contexts, e.g., slurry pipeline, fluidized beds, debris flows, sediment transport, etc. The one-way dispersed phase model (DPM), i.e., the conventional one-way coupling Euler-Lagrange method is not suitable for dense fluid-particle flows [1]. The reason is that such commercial CFD-software does not consider the contact between the fluid, particles and wall surfaces with respect to particle inertia and material properties. Hence, two-way coupling of the Dense Dispersed Phase Model (DDPM) combined with the Discrete Element Method (DEM) has been introduced into the commercial CFD software via in-house codes. As a result, more comprehensive and robust computational models based on the DDPM-DEM method have been developed, which can accurately predict the dynamics of dense particle suspensions.}, booktitle={Proceedings of the ASME International Mechanical Engineering Congress and Exposition, 2013, vol 3B}, author={Feng, Y. and Kleinstreuer, C.}, year={2014} } @article{childress_kleinstreuer_2014, title={Impact of Fluid-Structure Interaction on Direct Tumor-Targeting in a Representative Hepatic Artery System}, volume={42}, ISSN={["1573-9686"]}, DOI={10.1007/s10439-013-0910-7}, abstractNote={Direct targeting of solid tumors with chemotherapeutic drugs and/or radioactive microspheres can be a treatment option which minimizes side-effects and reduces cost. Briefly, computational analysis generates particle release maps (PRMs) which visually link upstream particle injection regions in the main artery with associated exit branches, some connected to tumors. The overall goal is to compute patient-specific PRMs realistically, accurately, and cost-effectively, which determines the suitable radial placement of a micro-catheter for optimal particle injection. Focusing in this paper on new steps towards realism and accuracy, the impact of fluid-structure interaction on direct drug-targeting is evaluated, using a representative hepatic artery system with liver tumor as a test bed. Specifically, the effect of arterial wall motion was demonstrated by modeling a two-way fluid-structure interaction analysis with Lagrangian particle tracking in the bifurcating arterial system. Clearly, rapid computational evaluation of optimal catheter location for tumor-targeting in a clinical application is very important. Hence, rigid-wall cases were also compared to the flexible scenario to establish whether PRMs generated when based on simplifying assumptions could provide adequate guidance towards ideal catheter placement. It was found that the best rigid (i.e., time-averaged) geometry is the physiological one that occurs during the diastolic targeting interval.}, number={3}, journal={ANNALS OF BIOMEDICAL ENGINEERING}, author={Childress, Emily M. and Kleinstreuer, Clement}, year={2014}, month={Mar}, pages={461–474} } @article{feng_kleinstreuer_2014, title={Micron-particle transport, interactions and deposition in triple lung-airway bifurcations using a novel modeling approach}, volume={71}, ISSN={["1879-1964"]}, DOI={10.1016/j.jaerosci.2014.01.003}, abstractNote={Particulate suspensions inhaled by humans are typically dilute and hence interactions between particles can be neglected. In such cases conventional Euler–Lagrange or Euler–Euler methods are suitable to simulate micron- or nano-particle transport and deposition in human respiratory systems. However, when challenging conditions, such as large pressure differentials, high velocity gradients and/or intense particle collisions, exist, alternative approaches for numerical analysis are required to capture fluid–particle, particle–particle, and particle–wall interactions. In the present study, the dense discrete phase model (DDPM) in conjunction with the discrete element method (DEM) have been employed to simulate micron–particle transport, interaction and deposition dynamics in different triple bifurcations (i.e., G3–G6, G6–G9, and G9–G12), using ANSYS Fluent 14.0 enhanced by user-defined functions (UDFs). In light of the relatively high computational cost when employing DDPM–DEM for such simulations throughout the human respiratory system, it may be necessary to combine different computational fluid–particle dynamics (CF–PD) models based on the local intensity of particle–particle interactions. Thus, the validity and necessity of the DDPM–DEM approach for different lung airway generations were numerically investigated, considering new parametric criteria for the use of most suitable numerical models. Specifically, the relative intensities of three major particle deposition mechanisms (i.e., inertial impaction, secondary-flow effect, and particle–particle-interaction impact) in idealized lung-airway segments were investigated. As a result, a new criterion for CF–PD model combination in terms of a relationship between inlet-particle stacking-volume fraction, ϕ, and percentage-of-fate changing particles, Δβp, is proposed. Visualizations of the fluid–particle dynamics in bifurcating airways have been provided as well. Results of this study pave the way for accurate and cost-effective CF–PD simulations of lung-aerosol dynamics, aiming at the improvement of respiratory dose estimation for health risk assessment in case of toxic particles and for treatment options in case of therapeutic particles.}, journal={JOURNAL OF AEROSOL SCIENCE}, author={Feng, Y. and Kleinstreuer, C.}, year={2014}, month={May}, pages={1–15} } @misc{mahian_kianifar_kleinstreuer_al-nimr_pop_sahin_wongwises_2013, title={A review of entropy generation in nanofluid flow}, volume={65}, ISSN={["1879-2189"]}, DOI={10.1016/j.ijheatmasstransfer.2013.06.010}, abstractNote={The development and use of nanofluids, i.e., dilute suspensions of nanoparticles in liquids, have found a wide range of applications in consumer products, nanomedicine, energy conversion, and microsystem cooling. Of special interest is the use of nanofluid flow for enhanced convection heat transfer to achieve rapid cooling of high heat-flux devices. However, for proper optimization of such thermal engineering systems in terms of design and operation, not only the heat transfer has to be maximized but the entropy generation has to be minimized as well. In this paper, theoretical and computational contributions on entropy generation due to flow and heat transfer of nanofluids in different geometries and flow regimes are reviewed. First, a variety of models used to calculate the thermophysical properties of nanofluids are presented. Then, the effects of thermal nanofluid flow on the rate of entropy generation for different applications are discussed. Finally, some suggestions for future work are presented. The aim of this review paper is to motivate the researchers to pay more attention to the entropy generation analysis of heat and fluid flow of nanofluids to improve the system performance.}, journal={INTERNATIONAL JOURNAL OF HEAT AND MASS TRANSFER}, author={Mahian, Omid and Kianifar, Ali and Kleinstreuer, Clement and Al-Nimr, Moh'd A. and Pop, Ioan and Sahin, Ahmet Z. and Wongwises, Somchai}, year={2013}, month={Oct}, pages={514–532} } @article{feng_kleinstreuer_2013, title={Analysis of non-spherical particle transport in complex internal shear flows}, volume={25}, ISSN={["1089-7666"]}, DOI={10.1063/1.4821812}, abstractNote={Focusing on ellipsoidal particles of different aspect ratios, the motion characteristics, including critical angle and stable vs. unstable rotational periods, are computationally analyzed in developing and fully developed tubular flows. As an application of particle transport and deposition, the one-way coupled Euler-Lagrange method enhanced by Euler's rotation equations is then employed to simulate laminar-turbulent flow in a subject-specific lung-airway model. First, to gain some basic insight into the dynamics of non-spherical particles, tubular flow is considered where the trajectories of ellipsoidal fibers with randomly initialized incidence angles were released at different inlet-plane positions, computed and visualized. Local and overall particle deposition results are compared between spheres, ellipsoidal fibers, and sphere-equivalent particles for which a revised Stokes diameter was developed. Concerning non-spherical particle transport and deposition in a subject-specific respiratory system, the validated computer simulation model provides realistic and accurate particle-deposition results. Specifically, slender non-spherical particles (i.e., those with higher aspect ratios) are potentially more harmful than thicker ones due to their ability to penetrate into deeper lung regions when somewhat aligned with the major flow field. Furthermore, non-spherical particle deposition is enhanced as the breathing rate increases.}, number={9}, journal={PHYSICS OF FLUIDS}, author={Feng, Y. and Kleinstreuer, C.}, year={2013}, month={Sep} } @misc{kleinstreuer_feng_2013, title={Computational Analysis of Non-Spherical Particle Transport and Deposition in Shear Flow With Application to Lung Aerosol Dynamics-A Review}, volume={135}, ISSN={["1528-8951"]}, DOI={10.1115/1.4023236}, abstractNote={All naturally occurring and most man-made solid particles are nonspherical. Examples include air-pollutants in the nano- to micro-meter range as well as blood constituents, drug particles, and industrial fluid-particle streams. Focusing on the modeling and simulation of inhaled aerosols, theories for both spherical and nonspherical particles are reviewed to analyze the contrasting transport and deposition phenomena of spheres and equivalent spheres versus ellipsoids and fibers.}, number={2}, journal={JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME}, author={Kleinstreuer, Clement and Feng, Yu}, year={2013}, month={Feb} } @article{han_lee_kleinstreuer_koo_2013, title={Critical Invalidation of Temperature Dependence of Nanofluid Thermal Conductivity Enhancement}, volume={135}, ISSN={["1528-8943"]}, DOI={10.1115/1.4023544}, abstractNote={Of interest is the accurate measurement of the enhanced thermal conductivity of certain nanofluids free from the impact of natural convection. Owing to its simplicity, wide range of applicability and short response time, the transient hot-wire method (THWM) is frequently used to measure the thermal conductivity of fluids. In order to gain a sufficiently high accuracy, special care should be taken to assure that each measurement is not affected by initial heat supply delay, natural convection, and signal noise. In this study, it was found that there is a temperature limit when using THWM due to the incipience of natural convection. The results imply that the temperature-dependence of the thermal conductivity enhancement observed by other researchers might be misleading when ignoring the impact of natural convection; hence, it could not be used as supporting evidence of the effectiveness of micromixing due to Brownian motion. Thus, it is recommended that researchers report how they keep the impact of the natural convection negligible and check the integrity of their measurements in the future researches.}, number={5}, journal={JOURNAL OF HEAT TRANSFER-TRANSACTIONS OF THE ASME}, author={Han, Kisoo and Lee, Wook-Hyun and Kleinstreuer, Clement and Koo, Junemo}, year={2013}, month={May} } @misc{kleinstreuer_feng_2013, title={Lung Deposition Analyses of Inhaled Toxic Aerosols in Conventional and Less Harmful Cigarette Smoke: A Review}, volume={10}, ISSN={["1660-4601"]}, DOI={10.3390/ijerph10094454}, abstractNote={Inhaled toxic aerosols of conventional cigarette smoke may impact not only the health of smokers, but also those exposed to second-stream smoke, especially children. Thus, less harmful cigarettes (LHCs), also called potential reduced exposure products (PREPs), or modified risk tobacco products (MRTP) have been designed by tobacco manufacturers to focus on the reduction of the concentration of carcinogenic components and toxicants in tobacco. However, some studies have pointed out that the new cigarette products may be actually more harmful than the conventional ones due to variations in puffing or post-puffing behavior, different physical and chemical characteristics of inhaled toxic aerosols, and longer exposure conditions. In order to understand the toxicological impact of tobacco smoke, it is essential for scientists, engineers and manufacturers to develop experiments, clinical investigations, and predictive numerical models for tracking the intake and deposition of toxicants of both LHCs and conventional cigarettes. Furthermore, to link inhaled toxicants to lung and other diseases, it is necessary to determine the physical mechanisms and parameters that have significant impacts on droplet/vapor transport and deposition. Complex mechanisms include droplet coagulation, hygroscopic growth, condensation and evaporation, vapor formation and changes in composition. Of interest are also different puffing behavior, smoke inlet conditions, subject geometries, and mass transfer of deposited material into systemic regions. This review article is intended to serve as an overview of contributions mainly published between 2009 and 2013, focusing on the potential health risks of toxicants in cigarette smoke, progress made in different approaches of impact analyses for inhaled toxic aerosols, as well as challenges and future directions.}, number={9}, journal={INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH}, author={Kleinstreuer, Clement and Feng, Yu}, year={2013}, month={Sep}, pages={4454–4485} } @article{kolanjiyil_kleinstreuer_2013, title={Nanoparticle Mass Transfer From Lung Airways to Systemic Regions-Part I: Whole-Lung Aerosol Dynamics}, volume={135}, ISSN={["1528-8951"]}, DOI={10.1115/1.4025332}, abstractNote={This is a two-part paper describing inhaled nanoparticle (NP) transport and deposition in a model of a human respiratory tract (Part I) as well as NP-mass transfer across barriers into systemic regions (Part II). Specifically, combining high-resolution computer simulation results of inhaled NP deposition in the human airways (Part I) with a multicompartmental model for NP-mass transfer (Part II) allows for the prediction of temporal NP accumulation in the blood and lymphatic systems as well as in organs. An understanding of nanoparticle transport and deposition in human respiratory airways is of great importance, as exposure to nanomaterial has been found to cause serious lung diseases, while the use of nanodrugs may have superior therapeutic effects. In Part I, the fluid-particle dynamics of a dilute NP suspension was simulated for the entire respiratory tract, assuming steady inhalation and planar airways. Thus, a realistic airway configuration was considered from nose/mouth to generation 3, and then an idealized triple-bifurcation unit was repeated in series and parallel to cover the remaining generations. Using the current model, the deposition of NPs in distinct regions of the lung, namely extrathoracic, bronchial, bronchiolar, and alveolar, was calculated. The region-specific NP-deposition results for the human lung model were used in Part II to determine the multicompartmental model parameters from experimental retention and clearance data in human lungs. The quantitative, experimentally validated results are useful in diverse fields, such as toxicology for exposure-risk analysis of ubiquitous nanomaterial as well as in pharmacology for nanodrug development and targeting.}, number={12}, journal={JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME}, author={Kolanjiyil, Arun V. and Kleinstreuer, Clement}, year={2013}, month={Dec} } @article{kolanjiyil_kleinstreuer_2013, title={Nanoparticle Mass Transfer From Lung Airways to Systemic Regions-Part II: Multi-Compartmental Modeling}, volume={135}, ISSN={["1528-8951"]}, DOI={10.1115/1.4025333}, abstractNote={This is the second article of a two-part paper, combining high-resolution computer simulation results of inhaled nanoparticle deposition in a human airway model (Kolanjiyil and Kleinstreuer, 2013, “Nanoparticle Mass Transfer From Lung Airways to Systemic Regions—Part I: Whole-Lung Aerosol Dynamics,” ASME J. Biomech. Eng., 135(12), p. 121003) with a new multicompartmental model for insoluble nanoparticle barrier mass transfer into systemic regions. Specifically, it allows for the prediction of temporal nanoparticle accumulation in the blood and lymphatic systems and in organs. The multicompartmental model parameters were determined from experimental retention and clearance data in rat lungs and then the validated model was applied to humans based on pharmacokinetic cross-species extrapolation. This hybrid simulator is a computationally efficient tool to predict the nanoparticle kinetics in the human body. The study provides critical insight into nanomaterial deposition and distribution from the lungs to systemic regions. The quantitative results are useful in diverse fields such as toxicology for exposure-risk analysis of ubiquitous nanomaterial and pharmacology for nanodrug development and targeting.}, number={12}, journal={JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME}, author={Kolanjiyil, Arun V. and Kleinstreuer, Clement}, year={2013}, month={Dec} } @article{richards_kleinstreuer_kennedy_childress_buckner_2012, title={Experimental Microsphere Targeting in a Representative Hepatic Artery System}, volume={59}, ISSN={["1558-2531"]}, DOI={10.1109/tbme.2011.2170195}, abstractNote={Recent work employing the computational fluid-particle modeling of the hepatic arteries has identified a correlation between particle release position and downstream branch distribution for direct tumor-targeting in radioembolization procedures. An experimental model has been constructed to evaluate the underlying simulation theory and determine its feasibility for future clinical use. A scaled model of a generalized hepatic system with a single inlet and five outlet branches was fabricated to replicate the fluid dynamics in the hepatic arteries of diseased livers. Assuming steady flow, neutrally buoyant microspheres were released from controlled locations within the inlet of the model and the resulting output distributions were recorded. Fluid and particle transport simulations were conducted with identical parameters. The resulting experimentally and simulation-derived microsphere distributions were compared. The experimental microsphere distribution exhibited a clear dependence on injection location that correlated very strongly with the computationally predicted results. Individual branch targeting was possible for each of the five outputs. The experimental results validate the simulation methodology for achieving targeted microsphere distributions in a known geometry under constant flow conditions.}, number={1}, journal={IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING}, author={Richards, Andrew L. and Kleinstreuer, Clement and Kennedy, Andrew S. and Childress, Emily and Buckner, Gregory D.}, year={2012}, month={Jan}, pages={198–204} } @article{zhang_kleinstreuer_hyun_2012, title={Size-change and deposition of conventional and composite cigarette smoke particles during inhalation in a subject-specific airway model}, volume={46}, ISSN={["1879-1964"]}, DOI={10.1016/j.jaerosci.2011.12.002}, abstractNote={In light of the established health risks of cigarette smoking, less harmful cigarettes (or potential reduced exposure products (PREPs)) have been marketed. Thus, it is of interest to analyze and compare the inhaled droplet dynamics of conventional and new composite cigarette smoke particles (CSPs). Inhalation pattern, hygroscopic growth and deposition of different composite cigarette smoke particles (CSPs) have been simulated numerically in a subject-specific human respiratory airway model from the mouth to generation G9. The validated computer model has been developed to consider the interaction of different deposition mechanisms, including impaction, sedimentation, diffusion, hygroscopic growth, coagulation, as well as possible cloud motion under different exposure and steady breathing conditions (e.g., puffing, post-puffing and two-step inhalation). The computer simulation results are consistent with numerous in-vivo and in-vitro studies as well as whole-lung modeling for deposition of conventional CSPs including hygroscopic growth and cloud motion. It is demonstrated that changes in cigarette composition significantly influence the hygroscopic growth of CSPs. In general, the growth rate of new composite CSPs is larger than the conventional one if the initial water mole-fraction is lower in the droplet. Hygroscopic growth of the new composite CSPs is not a significant mechanism leading to elevated deposition in the oral and tracheobronchial (TB) airways, provided that the relative humidity in the lungs does not exceed 99.5% and the droplet size does not exceed 3 μm; however, enhanced deposition may occur if the particles can grow over 3 μm. In this case, the deposition patterns of CSPs may be controlled by changing the primary composition, especially the initial ratio of water and glycerol. The simulation data with cloud diameters of 0.15–0.2 cm in the oral cavity and 0.5–0.6 cm in the trachea closely match the in-vivo lung deposition measurements of highly dense (conventional) CSPs. Specifically, preferred deposition occurs in the upper airway region, i.e., from the oral cavity to the second bifurcation, with deposition fractions of about 13–22% from the oral cavity to the larynx and 40–57% in the TB airways. This study is helpful for quantitatively evaluating the dose-exposure and subsequent health effects of both conventional and potentially less-harmful cigarettes.}, journal={JOURNAL OF AEROSOL SCIENCE}, author={Zhang, Zhe and Kleinstreuer, Clement and Hyun, Sinjae}, year={2012}, month={Apr}, pages={34–52} } @article{feng_kleinstreuer_2012, title={Thermal Nanofluid Property Model With Application to Nanofluid Flow in a Parallel Disk System-Part II: Nanofluid Flow Between Parallel Disks}, volume={134}, ISSN={["1528-8943"]}, DOI={10.1115/1.4005633}, abstractNote={This is the second part of a two-part paper which proposes a new theory explaining the experimentally observed enhancement of the thermal conductivity, knf, of nanofluids (Part I) and discusses simulation results of nanofluid flow in an axisymmetric jet-impingement cooling system using different knf-models (Part II). Specifically, Part II provides numerical simulations of convective nanofluid heat transfer in terms of velocity profiles, friction factor, temperature distributions, and Nusselt numbers, employing the new knf-model. Flow structures and the effects of nanoparticle addition on heat transfer and entropy generation are discussed as well. Analytical expressions for velocity profiles and friction factors, assuming quasi-fully-developed flow between parallel disks, have been derived and validated for nanofluids as well. Based on the numerical simulation results for both alumina-water nanofluids and pure water, it can be concluded that nanofluids show better heat transfer performance than convectional coolants with no great penalty in pumping power. Furthermore, the system’s entropy generation rate is lower for nanofluids than for pure water.}, number={5}, journal={JOURNAL OF HEAT TRANSFER-TRANSACTIONS OF THE ASME}, author={Feng, Yu and Kleinstreuer, Clement}, year={2012}, month={May} } @article{kleinstreuer_feng_2012, title={Thermal Nanofluid Property Model With Application to Nanofluid Flow in a Parallel-Disk System-Part I: A New Thermal Conductivity Model for Nanofluid Flow}, volume={134}, ISSN={["1528-8943"]}, DOI={10.1115/1.4005632}, abstractNote={This is a two-part paper, which proposes a new theory explaining the experimentally observed enhancement of the thermal conductivity, knf, of nanofluids (Part I) and discusses simulation results of nanofluid flow in a radial parallel-plate channel using different knf-models (Part II). Specifically, Part I provides the derivation of the new model as well as comparisons with benchmark experimental data sets and other theories, focusing mainly on aluminum and copper oxide nanoparticles in water. The new thermal conductivity expression consists of a base-fluid static part, kbf, and a new “micromixing” part, kmm, i.e., knf = kbf + kmm. While kbf relies on Maxwell’s theory, kmm encapsulates nanoparticle characteristics and liquid properties as well as Brownian-motion induced nanoparticle fluctuations, nanoparticle volume fractions, mixture-temperature changes, particle–particle interactions, and random temperature fluctuations causing liquid-particle interactions. Thus, fundamental physics principles include the Brownian-motion effect, an extended Langevin equation with scaled interaction forces, and a turbulence-inspired heat transfer equation. The new model predicts experimental data for several types of metal-oxide nanoparticles (20 < dp < 50 nm) in water with volume fractions up to 5% and mixture temperatures below 350 K. While the three competitive theories considered match selectively experimental data, their needs for curve-fitted functions and arbitrary parameters make these models not generally applicable. The new theory can be readily extended to accommodate other types of nanoparticle-liquid pairings and to include nonspherical nanomaterial.}, number={5}, journal={JOURNAL OF HEAT TRANSFER-TRANSACTIONS OF THE ASME}, author={Kleinstreuer, Clement and Feng, Yu}, year={2012}, month={May} } @article{zhang_kleinstreuer_feng_2012, title={Vapor deposition during cigarette smoke inhalation in a subject-specific human airway model}, volume={53}, ISSN={["1879-1964"]}, DOI={10.1016/j.jaerosci.2012.05.008}, abstractNote={Validated computer simulation results of vapor deposition from inhaled cigarette smoke are helpful to assess potential health effects of conventional and so-called less-harmful tobacco products. In this paper, the depositions of four critical tobacco-smoke vapors, i.e., acrolein, 1,3-butadiene, acetaldehyde and CO, in a subject-specific human airway model from mouth to generation G9 under different inhalation conditions have been simulated. The results show that vapor deposition is strongly influenced by its property values as well as inhalation waveform, i.e., puffing behavior. As almost insoluble species in the mucus layer, the deposition of butadiene vapor and CO is very low in the upper airways. The remaining vapors may penetrate further and deposit in deeper lung regions. As medium-to-high soluble vapors, acrolein and acetaldehyde have very high deposition values in the human upper airways from mouth to generation G9. The deposition result for steady matching flow (where the average flow rate between mean and peak values was taken) is a good conservative estimate of the actual deposition fraction under transient normal inhalation condition. However, the vapor transport delay may largely reduce the vapor deposition for transient puffing. A correction factor has been proposed, considering vapor transport delay, in order to calculate efficiently actual deposition fraction values under transient puffing condition. Furthermore, the effect of different puffing waveforms for conventional cigarettes and PREPs (potential reduced exposure products) on smoke vapor deposition has been discussed as well. Finally, a set of deposition correlations have been developed to estimate the deposition of acrolein and acetaldehyde vapors in different segments of the human upper airways under both puffing and normal inhalation (i.e., post-puffing) conditions.}, journal={JOURNAL OF AEROSOL SCIENCE}, author={Zhang, Zhe and Kleinstreuer, Clement and Feng, Yu}, year={2012}, month={Nov}, pages={40–60} } @article{basciano_kleinstreuer_hyun_finol_2011, title={A Relation Between Near-Wall Particle-Hemodynamics and Onset of Thrombus Formation in Abdominal Aortic Aneurysms}, volume={39}, ISSN={["0090-6964"]}, DOI={10.1007/s10439-011-0285-6}, abstractNote={A novel computational particle-hemodynamics analysis of key criteria for the onset of an intraluminal thrombus (ILT) in a patient-specific abdominal aortic aneurysm (AAA) is presented. The focus is on enhanced platelet and white blood cell residence times as well as their elevated surface-shear loads in near-wall regions of the AAA sac. The generalized results support the hypothesis that a patient's AAA geometry and associated particle-hemodynamics have the potential to entrap activated blood particles, which will play a role in the onset of ILT. Although the ILT history of only a single patient was considered, the modeling and simulation methodology provided allow for the development of an efficient computational tool to predict the onset of ILT formation in complex patient-specific cases.}, number={7}, journal={ANNALS OF BIOMEDICAL ENGINEERING}, author={Basciano, C. and Kleinstreuer, C. and Hyun, S. and Finol, E. A.}, year={2011}, month={Jul}, pages={2010–2026} } @article{li_kleinstreuer_2011, title={Airflow analysis in the alveolar region using the lattice-Boltzmann method}, volume={49}, ISSN={["1741-0444"]}, DOI={10.1007/s11517-011-0743-1}, abstractNote={A validated lattice-Boltzmann code has been developed based on the Bhatnagar-Gross-Krook formulation to simulate and analyze transient laminar two-dimensional airflow in alveoli and bifurcating alveolated ducts with moving walls, representative of the human respiratory zone. A physically more realistic pressure boundary condition has been implemented, considering a physiological Reynolds number range, i.e., 0 < Re < 11, which covers the inhalation scenarios from resting mode to moderate exercise. Axial velocity contours, vortex propagation, and streamlines as well as mid-plane pressure variations in different alveolar geometries and shapes are illustrated and discussed. The results show that the influence of the geometric structure on the airflow fields in the human alveolar region is very important. Furthermore, the effect of a moving alveolus wall is significant, i.e., the vortices in the duct or alveolar sacs may change in size. In summary, for a given set of realistic inlet conditions, the airflow velocity and vortical flows are greatly dependent on the different alveolar sac shapes, local geometric structures, and sac expansion rates. The pressure distributions are less influenced by the alveolus shape and wall movement. The present results provide new physical insight and are important for the simulation of particle transport/deposition in the deep lung region.}, number={4}, journal={MEDICAL & BIOLOGICAL ENGINEERING & COMPUTING}, author={Li, Z. and Kleinstreuer, C.}, year={2011}, month={Apr}, pages={441–451} } @article{li_sheeran_kleinstreuer_2011, title={Analysis of Multi-Layer Immiscible Fluid Flow in a Microchannel}, volume={133}, ISSN={["1528-901X"]}, DOI={10.1115/1.4005134}, abstractNote={The development of microfluidics platforms in recent years has led to an increase in the number of applications involving the flow of multiple immiscible layers of viscous electrolyte fluids. In this study, numerical results as well as analytic equations for velocity and shear stress profiles were derived for N layers with known viscosities, assuming steady laminar flow in a microchannel driven by pressure and/or electro-static (Coulomb) forces. Numerical simulation results, using a commercial software package, match analytical results for fully-developed flow. Entrance flow effects with centered fluid-layer shrinking were studied as well. Specifically, cases with larger viscosities in the inner layers show a very good agreement with experimental correlations for the dimensionless entrance length as a function of inlet Reynolds number. However, significant deviations may occur for multilayer flows with smaller viscosities in the inner layers. A correlation was deduced for the two-layer electroosmotic flow and the pressure driven flow, both being more complex when compared with single-layer flows. The impact of using power-law fluids on resulting velocity profiles has also been explored and compared to Newtonian fluid flows. The present model readily allows for an exploration of the impact of design choices on velocity profiles, shear stress, and channel distribution in multilayer microchannel flows as a function of layered viscosity distribution and type of driving force.}, number={11}, journal={JOURNAL OF FLUIDS ENGINEERING-TRANSACTIONS OF THE ASME}, author={Li, Jie and Sheeran, Paul S. and Kleinstreuer, Clement}, year={2011}, month={Nov} } @article{zhang_kleinstreuer_2011, title={Computational analysis of airflow and nanoparticle deposition in a combined nasal-oral-tracheobronchial airway model}, volume={42}, ISSN={["1879-1964"]}, DOI={10.1016/j.jaerosci.2011.01.001}, abstractNote={In light of the exponentially increasing industrial production and consumer use of ultrafine particles, deposition in the human lung is of great environmental and biomedical concern, especially for children, asthmatics and the elderly. Considering spherical nanoparticles in the 1–100 nm mean-diameter range and different breathing routes with Qtotal=30 and 60 L/min, local deposition fractions and global surface concentrations were predicted employing an experimentally validated computer simulation model. It was found that the change in breathing route (from nasal to oral breathing) not only significantly influences nanoparticle deposition in the regions of nasal and oral cavities, nasopharynx and oropharynx, but also measurably affects depositions from pharynx to bronchial airways for tiny nanoparticles (≤5 nm). The effect of breathing routes on deposition of larger nanoparticles (>5 nm) after the pharynx tends to be minor. The impact of different outlet flow-rate ratios generated by downstream resistances, e.g., caused by airway inflammation or tumors, is discussed in this study as well. Specifically, different outlet pressures primarily influence the velocity profiles and nanoparticle deposition fractions at that particular branch and adjacent bifurcations. In addition, the impact of change in outlet flow rate ratio on total deposition is confined to all same-level bifurcations and direct upstream-level bifurcations. The mass transfer coefficients of depositing nanoparticles (in terms of Sherwood number) can be well correlated as a function of Reynolds number and Schmidt number. The influence of downstream resistance on the Sherwood number in bronchial airways is smaller than intra-subject effects, i.e., variations of bifurcation levels and geometric parameters.}, number={3}, journal={JOURNAL OF AEROSOL SCIENCE}, author={Zhang, Zhe and Kleinstreuer, Clement}, year={2011}, month={Mar}, pages={174–194} } @article{zhang_kleinstreuer_2011, title={Deposition of naphthalene and tetradecane vapors in models of the human respiratory system}, volume={23}, ISSN={["1091-7691"]}, DOI={10.3109/08958378.2010.540261}, abstractNote={Jet-propulsion fuel (particularly JP-8) is currently being used worldwide, exposing especially Air Force personnel and people living near airfields to JP-8 vapors and aerosols during aircraft fueling, maintenance operations, and/or cold starts. JP-8 is a complex mixture containing >200, mostly toxic, aliphatic and aromatic hydrocarbon compounds of which tetradecane and naphthalene were chosen as two representative chemical markers for computer simulations. Thus, transport and deposition of naphthalene and tetradecane vapors have been simulated in models of the human respiratory system. The inspiratory deposition data were analyzed in terms of regional deposition fractions (DFs) and deposition enhancement factors (DEF). The vapor depositions are affected by vapor properties (e.g. diffusivity), airway geometric features, breathing patterns, inspiratory flow rates, as well as airway-wall absorption parameter. Specifically, the respiratory uptake of vapors is greatly influenced by the degree of airway-wall absorption. For example, being an almost insoluble species in the mucus layer, the deposition of tetradecane vapor is nearly zero in the extrathoracic and tracheobronchial (TB) airways, that is, the DF is <1%. The remaining vapors may penetrate further and deposit in the alveolar airways. The DF of tetradecane vapors during inhalation in the alveolar region can range from 7% to 24%, depending on breathing waveform, inhalation rate, and thickness of the mucus layer. In contrast, naphthalene vapor almost completely deposits in the extrathoracic and TB airways and hardly moves downstream and deposits in the respiratory zone. The DFs of naphthalene vapor in the extrathoracic airways from nasal/oral to trachea under normal breathing conditions (Q = 15–60 L/min) are about 12–34%, although they are about 66–87% in the TB airways. In addition, the variation of breathing routes (say, from nasal breathing to oral breathing) may influence the vapor deposition in the regions of nasal and oral cavities, nasopharynx and oropharynx, but hardly affects the deposition at and beyond the larynx. The different deposition patterns of naphthalene and tetradecane vapors in the human respiratory system may indicate different toxic and hence health effects of these toxic jet-fuel components.}, number={1}, journal={INHALATION TOXICOLOGY}, author={Zhang, Zhe and Kleinstreuer, Clement}, year={2011}, month={Jan}, pages={44–57} } @misc{kleinstreuer_feng_2011, title={Experimental and theoretical studies of nanofluid thermal conductivity enhancement: a review}, volume={6}, ISSN={["1556-276X"]}, DOI={10.1186/1556-276x-6-229}, abstractNote={Abstract}, journal={NANOSCALE RESEARCH LETTERS}, author={Kleinstreuer, Clement and Feng, Yu}, year={2011}, month={Mar} } @article{hong_kang_kleinstreuer_koo_2011, title={Impact analysis of natural convection on thermal conductivity measurements of nanofluids using the transient hot-wire method}, volume={54}, ISSN={["1879-2189"]}, DOI={10.1016/j.ijheatmasstransfer.2011.03.041}, abstractNote={Significant deviations between published results have been reported measuring the effective thermal conductivity of nanofluids with the transient hot-wire method (THWM). This may be attributed to a poor selection of the temperature data range, which should meet the following conditions. The start time should be chosen after the conductive heat flux delay time, while the end time should be selected before a crossover point when natural convection becomes significant. Considering an EG-based 1.06 vol.% ZnO nanofluid, the thermal conductivity was measured to increase by 5.4% over that of the base fluid.}, number={15-16}, journal={INTERNATIONAL JOURNAL OF HEAT AND MASS TRANSFER}, author={Hong, Sung Wook and Kang, Yong-Tae and Kleinstreuer, Clement and Koo, Junemo}, year={2011}, month={Jul}, pages={3448–3456} } @article{zhang_kleinstreuer_2011, title={Laminar-to-turbulent fluid-nanoparticle dynamics simulations: Model comparisons and nanoparticle-deposition applications}, volume={27}, ISSN={2040-7939}, url={http://dx.doi.org/10.1002/cnm.1447}, DOI={10.1002/cnm.1447}, abstractNote={SUMMARY}, number={12}, journal={International Journal for Numerical Methods in Biomedical Engineering}, publisher={Wiley}, author={Zhang, Zhe and Kleinstreuer, Clement}, year={2011}, month={May}, pages={1930–1950} } @article{kleinstreuer_zhang_2011, title={Optimal Drug-Aerosol Delivery to Predetermined Lung Sites}, volume={133}, ISSN={["1528-8943"]}, DOI={10.1115/1.4002224}, abstractNote={This review summarizes computer simulation methodologies of air-particle flow, results of drug-aerosol transport/deposition in models of the human respiratory system, as well as aspects of drug-aerosol targeting and associated inhalation devices. After a brief introduction to drug delivery systems in general, the required modeling and simulation steps for optimal drug-aerosol delivery in the lung are outlined. Starting with medical imaging and file conversion of patient-specific lung-airway morphologies, the air-particle transport phenomena are numerically solved for a representative inhalation flow rate of Qtotal=30 l/min. Focusing on microspheres and droplets, the complex airflow and particle dynamics, as well as the droplet heat and mass transfer are illustrated. With this foundation as the background, an overview of present inhaler devices is presented, followed by a discussion of the methodology and features of a new smart inhaler system (SIS). With the SIS, inhaled drug-aerosols can be directly delivered to any predetermined target area in the human lung.}, number={1}, journal={JOURNAL OF HEAT TRANSFER-TRANSACTIONS OF THE ASME}, author={Kleinstreuer, Clement and Zhang, Zhe}, year={2011}, month={Jan} } @article{kleinstreuer_zhang_2010, title={Airflow and Particle Transport in the Human Respiratory System}, volume={42}, ISSN={["0066-4189"]}, DOI={10.1146/annurev-fluid-121108-145453}, abstractNote={ Airflows in the nasal cavities and oral airways are rather complex, possibly featuring a transition to turbulent jet-like flow, recirculating flow, Dean's flow, vortical flows, large pressure drops, prevailing secondary flows, and merging streams in the case of exhalation. Such complex flows propagate subsequently into the tracheobronchial airways. The underlying assumptions for particle transport and deposition are that the aerosols are spherical, noninteracting, and monodisperse and deposit upon contact with the airway surface. Such dilute particle suspensions are typically modeled with the Euler-Lagrange approach for micron particles and in the Euler-Euler framework for nanoparticles. Micron particles deposit nonuniformly with very high concentrations at some local sites (e.g., carinal ridges of large bronchial airways). In contrast, nanomaterial almost coats the airway surfaces, which has implications of detrimental health effects in the case of inhaled toxic nanoparticles. Geometric airway features, as well as histories of airflow fields and particle distributions, may significantly affect particle deposition. }, journal={ANNUAL REVIEW OF FLUID MECHANICS}, author={Kleinstreuer, C. and Zhang, Z.}, year={2010}, pages={301–334} } @article{kennedy_kleinstreuer_basciano_dezarn_2010, title={COMPUTER MODELING OF YTTRIUM-90-MICROSPHERE TRANSPORT IN THE HEPATIC ARTERIAL TREE TO IMPROVE CLINICAL OUTCOMES}, volume={76}, ISSN={["0360-3016"]}, DOI={10.1016/j.ijrobp.2009.06.069}, abstractNote={