@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={Radioembolization (RE) via yttrium-90 ((90)Y) microspheres is an effective and safe treatment for unresectable liver malignancies. However, no data are available regarding the impact of local blood flow dynamics on (90)Y-microsphere transport and distribution in the human hepatic arterial system.A three-dimensional (3-D) computer model was developed to analyze and simulate blood-microsphere flow dynamics in the hepatic arterial system with tumor. Supplemental geometric and flow data sets from patients undergoing RE were also available to validate the accuracy of the computer simulation model. Specifically, vessel diameters, curvatures, and branching patterns, as well as blood flow velocities/pressures and microsphere characteristics (i.e., diameter and specific gravity), were measured. Three-dimensional computer-aided design software was used to create the vessel geometries. Initial trials, with 10,000 noninteracting microspheres released into the hepatic artery, used resin spheres 32-microm in diameter with a density twice that of blood.Simulations of blood flow subject to different branch-outlet pressures as well as blood-microsphere transport were successfully carried out, allowing testing of two types of microsphere release distributions in the inlet plane of the main hepatic artery. If the inlet distribution of microspheres was uniform (evenly spaced particles), a greater percentage would exit into the vessel branch feeding the tumor. Conversely, a parabolic inlet distribution of microspheres (more particles around the vessel center) showed a high percentage of microspheres exiting the branch vessel leading to the normal liver.Computer simulations of both blood flow patterns and microsphere dynamics have the potential to provide valuable insight on how to optimize (90)Y-microsphere implantation into hepatic tumors while sparing normal tissue.}, number={2}, journal={INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS}, author={Kennedy, Andrew S. and Kleinstreuer, Clement and Basciano, Christopher A. and Dezarn, William A.}, year={2010}, month={Feb}, pages={631–637} }
 @article{basciano_kleinstreuer_kennedy_dezarn_childress_2010, title={Computer Modeling of Controlled Microsphere Release and Targeting in a Representative Hepatic Artery System}, volume={38}, ISSN={["1573-9686"]}, DOI={10.1007/s10439-010-9955-z}, abstractNote={Combating liver tumors via yttrium-90 ((90)Y) radioembolization is a viable treatment option of nonresectable liver tumors. Employing clinical (90)Y microparticles (i.e., SIR-Spheres and TheraSpheres) in a computational model of a representative hepatic artery system, laminar transient 3D particle-hemodynamics were simulated. Specifically, optimal particle release positions in the right hepatic (parent) artery as well as the best temporal release window were determined for the microspheres to exit specific outlet daughter vessels, potentially connected to liver tumors. The results illustrate the influence of a curved geometry on the velocity field and the particle trajectory dependence on the spatial and temporal particle injection conditions. The differing physical particle characteristics of the SIR-Spheres and the TheraSpheres had a subtle impact on particle trajectories in the decelerating portion of the arterial pulse, i.e., when the inertial forces on the particles are weaker. Conversely, particle characteristics and inelastic wall collisions had little effect on particles released during the accelerating phase of the arterial pulse, i.e., both types of microspheres followed organized paths to predetermined outlets. Such results begin paving the way towards directing 100% of the released microspheres to specific daughter vessels (e.g., those connected to tumors) under transient flow conditions in realistic geometries via a novel drug-particle targeting methodology.}, number={5}, journal={ANNALS OF BIOMEDICAL ENGINEERING}, author={Basciano, Christopher A. and Kleinstreuer, Clement and Kennedy, Andrew S. and Dezarn, William A. and Childress, Emily}, year={2010}, month={May}, pages={1862–1879} }
 @article{shenoy_kleinstreuer_2010, title={Influence of aspect ratio on the dynamics of a freely moving circular disk}, volume={653}, ISSN={["0022-1120"]}, DOI={10.1017/s0022112010000418}, abstractNote={The influence of aspect ratio (χ = diameter/thickness) on the vortex shedding behaviour of fixed, and freely moving, circular disk has been investigated numerically. The aspect ratio significantly changes the structure of the vortices shed from the disk, thus altering the fluid induced forces. Disks of χ = 2 and 4 were selected, and by choosing Re = 240 periodic behaviour was observed for both the ‘fixed’ and ‘freely’ moving disks. First, the vortex structures shed from a ‘fixed’ circular disk of χ = 2 and 4 were computed for Re = 240. This was followed by a computation of their trajectories falling ‘freely’ under the action of gravity at Re = 240. For the ‘fixed’ disk of χ = 2, periodic shedding of one-sided hairpin-shaped vortex loops was observed. The flow field had a spatial planar symmetry and the vortices were shed from the same location, resulting in an asymmetric lateral force on the disk. The Strouhal number (St), calculated using the fluctuation in the axial velocity in the far-wake, was 0.122. This vortex shedding behaviour is referred to as the ‘single-sided’ vortex shedding mode. For the ‘fixed’ disk of χ = 4, periodic shedding of hairpin-shaped vortex loops was observed from the diametrically opposite location of the disk. The flow field had a spatial planar symmetry, and also a spatio-temporal one, with respect to a plane orthogonal to the spatial symmetry plane. The shed vortices induced a symmetric lateral force on the disk with a zero mean. The computed Strouhal number, was equal 0.122, same as that for χ = 2. This vortex shedding behaviour is referred as the ‘double-sided’ vortex shedding mode. For the ‘freely falling’ disk of χ = 2, an oscillatory motion was observed in a plane with a 83° phase lag between the lateral and angular velocity. The Strouhal number (Stb), calculated using the oscillation frequency of the ‘freely’ falling disk was equal to 0.116, which is comparable to the St of the fixed disk. For a ‘freely falling’ disk of χ = 4, oscillatory motion was observed in a plane with a 21° phase lag between the lateral and angular velocity. The Strouhal number (Stb) was equal to 0.171, which differs from the St observed in the wake of the fixed disk.}, journal={JOURNAL OF FLUID MECHANICS}, author={Shenoy, A. R. and Kleinstreuer, C.}, year={2010}, month={Jun}, pages={463–487} }
 @article{feng_kleinstreuer_2010, title={Nanofluid convective heat transfer in a parallel-disk system}, volume={53}, ISSN={["1879-2189"]}, DOI={10.1016/j.ijheatmasstransfer.2010.06.031}, abstractNote={Inherently low thermal conductivities of basic fluids form a primary limitation in high-performance cooling which is an essential requirement for numerous thermal systems and micro-devices. Nanofluids, i.e., dilute suspensions of, say, metal-oxide nanoparticles in a liquid, are a new type of coolants with better heat transfer performances than their pure base fluids alone. Using a new, experimentally validated model for the thermal conductivity of nanofluids, numerical simulations have been executed for alumina-water nanofluid flow with heat transfer between parallel disks. The results indicate that, indeed, nanofluids are promising new coolants when compared to pure water. Specifically, smoother mixture flow fields and temperature distributions can be achieved. More importantly, given a realistic thermal load, the Nusselt number increases with higher nanoparticle volume fraction, smaller nanoparticle diameter, reduced disk-spacing, and, of course, larger inlet Reynolds number, expressed in a novel form as Nu = Nu(Re and Br). Fully-developed flow can be assumed after a critical radial distance, expressed in a correlation Rcrit = fct(Re), has been reached and hence analytic solutions provide good approximations. Nanofluids reduce the system’s total entropy generation rate while hardly increasing the required pumping power for any given Rein. Specifically, minimization of total entropy generation allows for operational and geometric system-optimization in terms of Sgen = fct (Re and δ).}, number={21-22}, journal={INTERNATIONAL JOURNAL OF HEAT AND MASS TRANSFER}, author={Feng, Yu and Kleinstreuer, Clement}, year={2010}, month={Oct}, pages={4619–4628} }
 @article{kleinstreuer_zhang_2009, title={An Adjustable Triple-Bifurcation Unit Model for Air-Particle Flow Simulations in Human Tracheobronchial Airways}, volume={131}, ISSN={["1528-8951"]}, DOI={10.1115/1.3005339}, abstractNote={A new methodology for a swift and accurate computer simulation of large segments of the human lung airways is presented. Focusing on a representative tracheobronchial (TB) region, i.e., G0–G15, nano- and micron particle transports have been simulated for Qin=30l∕min, employing an experimentally validated computer model. The TB tree was geometrically decomposed into triple-bifurcation units with kinematically adjusted multilevel outlet/inlet conditions. Deposition patterns and maximum concentrations differ greatly between nanoparticles (1⩽dp⩽150nm) and micron particles (1⩽dp⩽10μm), which may relate uniquely to health impacts. In comparison with semi-analytical particle deposition results, it is shown that such simple “lung models” cannot predict local deposition values but can match computer simulation results for the entire TB region within 2.5–26%. The present study revealed that turbulent air-particle flow may propagate to G5 for the assumed inhalation flow rate. Geometry and upstream effects are more pronounced for micron particle deposition than for nanoparticle deposition.}, number={2}, journal={JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME}, author={Kleinstreuer, C. and Zhang, Z.}, year={2009}, month={Feb} }
 @article{zhang_kleinstreuer_kim_2009, title={Comparison of analytical and CFD models with regard to micron particle deposition in a human 16-generation tracheobronchial airway model}, volume={40}, ISSN={["1879-1964"]}, DOI={10.1016/j.jaerosci.2008.08.003}, abstractNote={A representative human tracheobronchial tree has been geometrically represented with adjustable triple-bifurcation units (TBUs) in order to effectively simulate local and global micron particle depositions. It is the first comprehensive attempt to compute micron-particle transport in a (Weibel Type A) 16-generation model with realistic inlet conditions. The CFD modeling predictions are compared to experimental observations as well as analytical modeling results. Based on the findings with the validated computer simulation model, the following conclusions can be drawn: (i) Surprisingly, simulated inspiratory deposition fractions for the entire tracheobronchial region (say, G0–G15) with repeated TBUs in parallel and in series agree rather well with those calculated using analytical/semi-empirical expressions. However, the predicted particle-deposition fractions based on such analytical formulas differ greatly from the present simulation results for most local bifurcations, due to the effects of local geometry and resulting local flow features and particle distributions. Clearly, the effects of realistic geometries, flow structures and particle distributions in different individual bifurcations accidentally cancel each other so that the simulated deposition efficiencies during inspiration in a relatively large airway region may agree quite well with those obtained from analytical expressions. Furthermore, with the lack of local resolution, analytical models do not provide any physical insight to the air–particle dynamics in the tracheobronchial region. (ii) The maximum deposition enhancement factors (DEF) may be in the order of 102 to 103 for micron particles in the tracheobronchial airways, implying potential health effects when the inhaled particles are toxic. (iii) The presence of sedimentation for micron particles in lower bronchial airways may change the local impaction-based deposition patterns seen for larger airways and hence reduces the maximum DEF values. (iv) Rotation of an airway bifurcation cause a significant impact on distal bifurcations rather than on the proximal ones. Such geometric effects are minor when compared to the effects of airflow and particle transport/deposition history, i.e., upstream effects.}, number={1}, journal={JOURNAL OF AEROSOL SCIENCE}, author={Zhang, Zhe and Kleinstreuer, Clement and Kim, Chong S.}, year={2009}, month={Jan}, pages={16–28} }
 @article{basciano_kleinstreuer_2009, title={Invariant-Based Anisotropic Constitutive Models of the Healthy and Aneurysmal Abdominal Aortic Wall}, volume={131}, ISSN={["1528-8951"]}, DOI={10.1115/1.3005341}, abstractNote={The arterial wall is a complex fiber-reinforced composite. Pathological conditions, such as aneurysms, significantly alter the mechanical response of the arterial wall, resulting in a loss of elasticity, enhanced anisotropy, and increased chances of mechanical failure. Invariant-based models of the healthy and aneurysmal abdominal aorta were constructed based on first principles and published experimental data with implementations for several numerical cases, as well as comparisons to current healthy and aneurysmal tissue data. Inherent limitations of a traditional invariant-based methodology are also discussed and compared to the models’ ability to accurately reproduce experimental trends. The models capture the nonlinear and anisotropic mechanical responses of the two arterial sections and make reasonable predictions regarding the effects of alterations in healthy and diseased tissue histology. Additionally, the new models exhibit convex and anisotropic monotonically increasing energy contours (suggesting numerical stability) but have potentially the inherent limitations of a covariant theoretical framework. Although the traditional invariant framework exhibits significant covariance, the invariant terms utilized in the new models exhibited limited covariance and are able to accurately reproduce experimental trends. A streamlined implementation is also possible for future numerical investigations of fluid-structure interactions in abdominal aortic aneurysms.}, number={2}, journal={JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME}, author={Basciano, C. A. and Kleinstreuer, C.}, year={2009}, month={Feb} }
 @article{li_kleinstreuer_2009, title={Microfluidics analysis of nanoparticle mixing in a microchannel system}, volume={6}, ISSN={["1613-4990"]}, DOI={10.1007/s10404-008-0341-1}, number={5}, journal={MICROFLUIDICS AND NANOFLUIDICS}, author={Li, Jie and Kleinstreuer, Clement}, year={2009}, month={May}, pages={661–668} }
 @article{kleinstreuer_zhang_li_roberts_rojas_2008, title={A new methodology for targeting drug-aerosols in the human respiratory system}, volume={51}, ISSN={["1879-2189"]}, DOI={10.1016/j.ijheatmasstransfer.2008.04.052}, abstractNote={Inhalation of medicine for the treatment of lung and other diseases is becoming more and more a preferred option when compared to injection or oral intake. Unfortunately, existing devices such as the popular pressurized metered dose inhalers and dry powder inhalers have rather low deposition efficiencies and their drug-aerosol deliveries are non-directional. This is acceptable when the medicine is inexpensive and does not cause systemic side effects, as it may be the case for patients with mild asthma. However, the delivery of aggressive chemicals, or expensive insulin, vaccines and genetic material embedded in porous particles or droplets requires optimal targeting of such inhaled drug-aerosols to predetermined lung areas. The new methodology introduces the idea of a controlled air-particle stream which provides maximum, patient-specific drug-aerosol deposition based on optimal particle diameter and density, inhalation waveform, and particle-release position. The efficacy of the new methodology is demonstrated with experimentally validated computer simulations of two-phase flow in a human oral airway model with two different sets of tracheobronchial airways. Physical insight to the dynamics of the controlled air-particle stream is provided as well.}, number={23-24}, journal={INTERNATIONAL JOURNAL OF HEAT AND MASS TRANSFER}, author={Kleinstreuer, Clement and Zhang, Zhe and Li, Zheng and Roberts, William L. and Rojas, Carlye}, year={2008}, month={Nov}, pages={5578–5589} }
 @article{koo_kang_kleinstreuer_2008, title={A nonlinear effective thermal conductivity model for carbon nanotube and nanofiber suspensions}, volume={19}, ISSN={["1361-6528"]}, DOI={10.1088/0957-4484/19/37/375705}, abstractNote={It has been experimentally demonstrated that suspensions of carbon nanotubes (CNTs) and nanofibers (CNFs) significantly increase the thermal conductivity of nanofluids; however, a physically sound theory of the underlying phenomenon is still missing. In this study, the nonlinear nature of the effective thermal conductivity enhancement with the particle concentration of CNT and CNF nanofluids is explained physically using the excluded volume concept. Specifically, the number of contacting CNTs and CNFs could be calculated by using the excluded volume concept, where the distance for heat to travel in a cylinder between the contacting cylinders in the thermal network of percolating CNTs and CNFs increased with the excluded volume. In contrast to the effective thermal conductivity model of Sastry et al (2008 Nanotechnology 19 055704) the present revised model could reproduce the nonlinear increase of the thermal conductivity with particle concentration, as well as the dependence on the diameter and aspect ratio of the CNTs and CNFs. It was found that the alignment of CNTs and CNFs due to the long range repulsion force decreases the excluded volume, leading to both the convex and concave nonlinear as well as linear increase of the thermal conductivity with particle concentration. The difference between various carrier fluids of the suspensions could be explained as the result of the change in the excluded volume in different base fluids.}, number={37}, journal={NANOTECHNOLOGY}, author={Koo, J. and Kang, Y. and Kleinstreuer, C.}, year={2008}, month={Sep} }
 @article{zhang_kleinstreuer_kim_2008, title={Airflow and Nanoparticle Deposition in a 16-Generation Tracheobronchial Airway Model}, volume={36}, ISSN={["1573-9686"]}, DOI={10.1007/s10439-008-9583-z}, abstractNote={In order to achieve both manageable simulation and local accuracy of airflow and nanoparticle deposition in a representative human tracheobronchial (TB) region, the complex airway network was decomposed into adjustable triple-bifurcation units, spreading axially and laterally. Given Q(in) = 15 and 30 L/min and a realistic inlet velocity profile, the experimentally validated computer simulation model provided some interesting 3-D airflow patterns, i.e., for each TB-unit they depend on the upstream condition, local geometry and local Reynolds number. Directly coupled to the local airflow fields are the convective-diffusive transport and deposition of nanoparticles, i.e., 1 nm < or = d(p) < or = 100 nm. The CFD modeling predictions were compared to experimental observations as well as analytical modeling results. The CFD-simulated TB deposition values agree astonishingly well with analytical modeling results. However, measurable differences can be observed for bifurcation-by-bifurcation deposition fractions obtained with these two different approaches due to the effects of more realistic inlet conditions and geometric features incorporated in the CFD model. Specifically, while the difference between the total TB deposition fraction (DF) is less than 16%, it may be up to 70% for bifurcation-by-bifurcation DFs. In addition, it was found that fully developed flow and uniform nanoparticle concentrations can be assumed beyond generation G12. For nanoparticles with d(p) > 10 nm, the geometric effects, including daughter-branch rotation, are minor. Furthermore, the deposition efficiencies at each individual bifurcation in the TB region can be well correlated as a function of an effective diffusion parameter.}, number={12}, journal={ANNALS OF BIOMEDICAL ENGINEERING}, author={Zhang, Zhe and Kleinstreuer, Clement and Kim, Chong S.}, year={2008}, month={Dec}, pages={2095–2110} }
 @article{kleinstreuer_li_basciano_seelecke_farber_2008, title={Computational mechanics of Nitinol stent grafts}, volume={41}, ISSN={["1873-2380"]}, DOI={10.1016/j.jbiomech.2008.05.032}, abstractNote={A finite element analysis of tubular, diamond-shaped stent grafts under representative cyclic loading conditions for abdominal aortic aneurysm (AAA) repair is presented. Commercial software was employed to study the mechanical behavior and fatigue performance of different materials found in commercially available stent-graft systems. Specifically, the effects of crimping, deployment, and cyclic pressure loading on stent-graft fatigue life, radial force, and wall compliances were simulated and analyzed for two types of realistic but different Nitinol materials (NITI-1 and NITI-2) and grafts (expanded polytetrafluoroethylene-ePTFE and polyethylene therephthalate-PET). The results show that NITI-1 stent has a better crimping performance than NITI-2. Under representative cyclic pressure loading, both NITI-1 and NITI-2 sealing stents are located in the safe zone of the fatigue-life diagram; however, the fatigue resistance of an NITI-1 stent is better than that of an NITI-2 stent. It was found that the two types of sealing stents do not damage a healthy neck artery. In the aneurysm section, the NITI-1&ePTFE, NITI-1&PET, and NITI-2&PET combinations were free of fatigue fracture when subjected to conditions of radial stress between 50 and 150mmHg. In contrast, the safety factor for the NITI-2&ePFTE combination was only 0.67, which is not acceptable for proper AAA stent-graft design. In summary, a Nitinol stent with PET graft may greatly improve fatigue life, while its compliance is much lower than the NITI-ePTFE combination.}, number={11}, journal={JOURNAL OF BIOMECHANICS}, author={Kleinstreuer, C. and Li, Z. and Basciano, C. A. and Seelecke, S. and Farber, M. A.}, year={2008}, month={Aug}, pages={2370–2378} }
 @article{shi_kleinstreuer_zhang_2008, title={Dilute suspension flow with nanoparticle deposition in a representative nasal airway model}, volume={20}, ISSN={["1089-7666"]}, DOI={10.1063/1.2833468}, abstractNote={The human nasal cavities with an effective length of only 10cm feature a wide array of basic flow phenomena because of their complex geometrics. Employing a realistic nasal airway model and demonstrating that laminar, quasisteady airflow can be assumed, dilute nanoparticle suspension flow and nanoparticle deposition are simulated and analyzed for 7.5⩽Q⩽20L∕min and 1⩽dp⩽150nm. The understanding and quantitative assessment of mixture flow fields and local nanoparticle wall concentrations in nasal airways with a thin mucus layer are very important for estimating the health risks of inhaled toxic aerosols, determining proper drug-aerosol delivery to target sites such as the olfactory regions and developing algebraic transfer functions for overall nasal dose-response analyses. Employing a commercial software package with user-supplied programs, the validated computer modeling results can be summarized as follows: (i) Most of the air flows through the middle-to-low main passageways. Higher airflow rates result in stronger airflow in the olfactory region and relatively lower flow rates in the meatuses. (ii) Nanoparticle deposition in human nasal airways is significant for tiny nanoparticles, i.e., 1⩽dp⩽2nm, which also represent some vapors. The smaller the nanoparticle size and the lower the flow rate, the higher are the total deposition efficiencies because of stronger diffusion and longer residence times. (iii) Nanoparticles with dp<5nm flow preferentially through the middle-to-low main passageway along with the major portion of the airflow. For relatively large nanoparticles (dp⩾5nm), due to the low diffusivities, fewer particles will deposit onto the wall leaving a much thinner nanoparticle gradient layer near the wall, i.e., such nanoparticles pass through the nasal cavities more uniformly with minor wall deposition. (iv) Secondary flows may enhance nanoparticle transport and deposition, especially in the meatuses by convecting nanoparticles into these particular regions. (v) For the olfactory region, an optimal particle size may exist due to the combined effects of nanoparticle transport and local deposition mechanisms. However, because of the low deposition flux and small surface area, the olfactory channels account for only very small total deposition values. (vi) A compact correlation for predicting nanoparticle deposition in human nasal airways has been developed.}, number={1}, journal={PHYSICS OF FLUIDS}, author={Shi, H. and Kleinstreuer, C. and Zhang, Z.}, year={2008}, month={Jan} }
 @article{kleinstreuer_li_2008, title={Discussion: "Effects of various parameters on nanotluid thermal conductivity" ( Jang, S.P., and Choi, S.D.S., 2007, ASME J. heat transfer, 129, pp. 617-623)}, volume={130}, ISSN={["1528-8943"]}, DOI={10.1115/1.2812307}, abstractNote={In a series of articles, Jang and Choi 1–3 listed and explained heir effective thermal conductivity keff model for nanofluids. or example, in the 2004 article 1 , they constructed a keff correation for dilute liquid suspensions interestingly, based on kinetic as theory as well as nanosize boundary-layer theory, the Kapitza esistance, and nanoparticle-induced convection. Three mechaisms contributing to keff were summed up, i.e., base-fluid and anoparticle conductions as well as convection due to random otion of the liquid molecules. Thus, after an order-of-magnitude nalysis, their effective thermal conductivity model of nanofluids eads}, number={2}, journal={JOURNAL OF HEAT TRANSFER-TRANSACTIONS OF THE ASME}, author={Kleinstreuer, C. and Li, Jie}, year={2008}, month={Feb} }
 @article{shenoy_kleinstreuer_2008, title={Flow over a thin circular disk at low to moderate Reynolds numbers}, volume={605}, ISSN={["1469-7645"]}, DOI={10.1017/S0022112008001626}, abstractNote={Computation of viscous flow over a circular disk of aspect ratio 10 (thickness/diameter) in the Reynolds number (Re) range of 10 to 300 was performed. The following flow regimes were observed: (I) steady axisymmetric flow whenRe< 135, with the presence of a toroidal vortex behind the disk; (II) regular bifurcation with loss of azimuthal symmetry but with planar symmetry and a double-threaded wake, for 135 ≤Re< 155; (III) three-dimensional flow with periodic shedding of double-sided hairpin-shaped vortex structures and periodic motion of the separation region for 155 ≤Re< 172; (IV) regular shedding of double-sided hairpin-shaped vortex structures with planar and spatio-temporal symmetry for 172 ≤Re< 280; (V) periodic three-dimensional flow with irregular rotation of the separation region whenRe= 280–300. This transition process for the disk differs from that for the sphere as we observe a loss of the symmetry plane in Regime III due to a twisting motion of the axial vorticity strands in the wake of the disk. The periodic flow was characterized by double-sided hairpin structures, unlike the one-sided vortex loops observed for the sphere. This resulted in the drag coefficient oscillating at twice the frequency of the axial velocity. In Regime IV, the vortex loops were shed from diametrically opposite locations and with equal strength, resulting in the lift coefficient oscillating symmetrically about a zero mean. These results imply the presence of spatio-temporal symmetry.}, journal={JOURNAL OF FLUID MECHANICS}, author={Shenoy, A. R. and Kleinstreuer, C.}, year={2008}, month={Jun}, pages={253–262} }
 @article{kleinstreuer_li_koo_2008, title={Microfluidics of nano-drug delivery}, volume={51}, ISSN={["1879-2189"]}, DOI={10.1016/j.ijheatmasstransfer.2008.04.043}, abstractNote={After a brief review of microfluidics, a bio-MEMS application in terms of nanofluid flow in microchannels is presented. Specifically, the transient 3-D problem of controlled nano-drug delivery in a heated microchannel has been numerically solved to gain new physical insight and to determine suitable geometric and operational system parameters. Computer model accuracy was verified via numerical tests and comparisons with benchmark experimental data sets. The overall design goals of near-uniform nano-drug concentration at the microchannel exit plane and desired mixture fluid temperature were achieved with computer experiments considering different microchannel lengths, nanoparticle diameters, channel flow rates, wall heat flux areas, and nanofluid supply rates. Such micro-systems, featuring controlled transport processes for optimal nano-drug delivery, are important in laboratory-testing of predecessors of implantable smart devices as well as for analyzing pharmaceuticals and performing biomedical precision tasks.}, number={23-24}, journal={INTERNATIONAL JOURNAL OF HEAT AND MASS TRANSFER}, author={Kleinstreuer, Clement and Li, Jie and Koo, Junemo}, year={2008}, month={Nov}, pages={5590–5597} }
 @misc{kleinstreuer_zhang_li_2008, title={Modeling airflow and particle transport/deposition in pulmonary airways}, volume={163}, ISSN={["1878-1519"]}, DOI={10.1016/j.resp.2008.07.002}, abstractNote={A review of research papers is presented, pertinent to computer modeling of airflow as well as nano- and micron-size particle deposition in pulmonary airway replicas. The key modeling steps are outlined, including construction of suitable airway geometries, mathematical description of the air-particle transport phenomena and computer simulation of micron and nanoparticle depositions. Specifically, diffusion-dominated nanomaterial deposits on airway surfaces much more uniformly than micron particles of the same material. This may imply different toxicity effects. Due to impaction and secondary flows, micron particles tend to accumulate around the carinal ridges and to form "hot spots", i.e., locally high concentrations which may lead to tumor developments. Inhaled particles in the size range of 20nm< or =dp< or =3microm may readily reach the deeper lung region. Concerning inhaled therapeutic particles, optimal parameters for mechanical drug-aerosol targeting of predetermined lung areas can be computed, given representative pulmonary airways.}, number={1-3}, journal={RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY}, author={Kleinstreuer, Clement and Zhang, Zhe and Li, Zheng}, year={2008}, month={Nov}, pages={128–138} }
 @article{kleinstreuer_zhang_donohue_2008, title={Targeted drug-aerosol delivery in the human respiratory system}, volume={10}, ISSN={["1545-4274"]}, DOI={10.1146/annurev.bioeng.10.061807.160544}, abstractNote={ Inhalation of drug aerosols is a modern pathway to combat lung diseases. It is also becoming the preferred route for insulin delivery, pain management, cancer therapy, and nanotherapeutics. Popular delivery devices include nebulizers, metered-dose inhalers, and dry-powder inhalers. They are all nondirectional and hence have typically low particle deposition efficiencies in desired nasal or lung areas. Thus, for specific disease treatment with costly and/or aggressive medicine, it is necessary to provide targeted drug–aerosol delivery to predetermined sites in the human respiratory system. Experimental measurements and computer models of particle transport and deposition in nasal and lung airway models are presented. Furthermore, the underlying methodology and performance of pressurized metered dose inhalers as well as new smart inhaler systems are discussed. To maximize respiratory drug delivery to specific sites, an optimal combination of particle characteristics, inhalation waveform, particle release position, and drug-aerosol dosage has to be achieved. }, journal={ANNUAL REVIEW OF BIOMEDICAL ENGINEERING}, author={Kleinstreuer, C. and Zhang, Z. and Donohue, J. F.}, year={2008}, pages={195–220} }
 @article{li_kleinstreuer_2008, title={Thermal performance of nanofluid flow in microchannels}, volume={29}, ISSN={["1879-2278"]}, DOI={10.1016/j.ijheatfluidflow.2008.01.005}, abstractNote={Two effective thermal conductivity models for nanofluids were compared in detail, where the new KKL (Koo–Kleinstreuer–Li) model, based on Brownian motion induced micro-mixing, achieved good agreements with the currently available experimental data sets. Employing the commercial Navier–Stokes solver CFX-10 (Ansys Inc., Canonsburg, PA) and user-supplied pre- and post-processing software, the thermal performance of nanofluid flow in a trapezoidal microchannel was analyzed using pure water as well as a nanofluid, i.e., CuO–water, with volume fractions of 1% and 4% CuO-particles with dp = 28.6 nm. The results show that nanofluids do measurably enhance the thermal performance of microchannel mixture flow with a small increase in pumping power. Specifically, the thermal performance increases with volume fraction; but, the extra pressure drop, or pumping power, will somewhat decrease the beneficial effects. Microchannel heat sinks with nanofluids are expected to be good candidates for the next generation of cooling devices.}, number={4}, journal={INTERNATIONAL JOURNAL OF HEAT AND FLUID FLOW}, author={Li, Jie and Kleinstreuer, Clement}, year={2008}, month={Aug}, pages={1221–1232} }
 @article{li_kleinstreuer_2007, title={A comparison between different asymmetric abdominal aortic aneurysm morphologies employing computational fluid-structure interaction analysis}, volume={26}, ISSN={["1873-7390"]}, DOI={10.1016/j.euromechflu.2007.03.003}, abstractNote={Considering representative asymmetric aneurysms in the abdominal aorta, the transient 3-D blood flow and pressure distributions as well as aneurysm wall stresses were numerically analyzed. To obtain more realistic and accurate results for blood flow fields and wall stress distributions, a coupled fluid-flow and solid–structure solver was employed. Geometric abdominal aortic aneurysm (AAA) variations studied included the degree of asymmetry, neck angle and bifurcation angle, and hence their impacts on the hemodynamics and biomechanics. The simulation results indicated that the assumption of symmetric AAA geometry may underestimate AAA-wall stress considerably. The neck angle influences the blood flow field substantially. A large neck angle, resulting in strong wall curvatures near the proximal neck, can produce aggravating blood flow patterns and elevated wall stresses (Von Mises). The iliac bifurcation angle affects blood flow patterns insignificantly but plays an important role in wall-stress concentrations. The wall stress of lateral asymmetric AAAs is higher than for the anterior-posterior asymmetric types. The maximum wall stress-site is located near the anterior distal side for the anterior-posterior asymmetric AAA and the distal side towards the asymmetric bulge in the lateral asymmetric AAA.}, number={5}, journal={EUROPEAN JOURNAL OF MECHANICS B-FLUIDS}, author={Li, Zhonghua and Kleinstreuer, Clement}, year={2007}, pages={615–631} }
 @article{kleinstreuer_zhang_kim_2007, title={Combined inertial and gravitational deposition of microparticles in small model airways of a human respiratory system}, volume={38}, ISSN={["1879-1964"]}, DOI={10.1016/j.jaerosci.2007.08.010}, abstractNote={Focusing on relatively small airways in terms of the medium-size bronchial generations G6–G9, the interplay of impaction and sedimentation on micron particle transport and deposition has been simulated. A commercial finite-volume code, enhanced with user-supplied programs, has been employed. Although impaction is still a dominant deposition mechanism for microparticle in medium-size airways under normal breathing conditions (say, Qin=15–30L/min), sedimentation may play a role as well. In turn, that can influence the local particle deposition patterns, efficiencies and fractions for a realistic range of Stokes numbers (0.001⩽St⩽0.33). However, deposition due to sedimentation is significantly amplified during slow inhalation; for example, the gravitational deposition may become dominant in the ninth bifurcation (i.e., generations G8–G9) for relatively large microparticles (say, dp>5μm) at Qin=3.75L/min. The occurrence of sedimentation changes the location of the deposition “hot spots” and reduces the order of the maximum deposition enhancement factor. The use of analytical formulas based on inclined tube models for predicting gravitational deposition in local bronchial airway segments as well as the combination of deposition by sedimentation and impaction has to be carefully examined. As shown, more prudent is the use of curve-fitted correlations generated from experimentally validated computer simulation results as a function of Stokes number and sedimentation parameter.}, number={10}, journal={JOURNAL OF AEROSOL SCIENCE}, author={Kleinstreuer, Clement and Zhang, Zhe and Kim, Chong S.}, year={2007}, month={Oct}, pages={1047–1061} }
 @article{kleinstreuer_shi_zhang_2007, title={Computational analyses of a pressurized metered dose inhaler and a new drug-aerosol targeting methodology}, volume={20}, ISSN={["0894-2684"]}, DOI={10.1089/jam.2006.0617}, abstractNote={The popular pressurized metered dose inhaler (pMDI), especially for asthma treatment, has undergone various changes in terms of propellant use and valve design. Most significant are the choice of hydrofluoroalkane-134a (HFA-134a) as a new propellant (rather than chlorofluorocarbon, CFC), a smaller exit nozzle diameter and attachment of a spacer in order to reduce ultimately droplet size and spray inhalation speed, both contributing to higher deposition efficiencies and hence better asthma therapy. Although asthma medicine is rather inexpensive, the specter of systemic side effects triggered by inefficient pMDI performance and the increasing use of such devices as well as new targeted drug-aerosol delivery for various lung and other diseases make detailed performance analyses imperative. For the first time, experimentally validated computational fluid-particle dynamics technique has been applied to simulate airflow, droplet spray transport and aerosol deposition in a pMDI attached to a human upper airway model, considering different device propellants, nozzle diameters, and spacer use. The results indicate that the use of HFA (replacing CFC), smaller valve orifices (0.25 mm instead of 0.5 mm) and spacers (ID = 4.2 cm) leads to best performance mainly because of smaller droplets generated, which penetrate more readily into the bronchial airways. Experimentally validated computer simulations predict that 46.6% of the inhaled droplets may reach the lung for an HFA-pMDI and 23.2% for a CFC-pMDI, both with a nozzle-exit diameter of 0.25 mm. Commonly used inhalers are nondirectional, and at best only regional drug-aerosol deposition can be achieved. However, when inhaling expensive and aggressive medicine, or critical lung areas have to be reached, locally targeted drug-aerosol delivery is imperative. For that reason the underlying principle of a future line of "smart inhalers" is introduced. Specifically, by generating a controlled air-particle stream, most of the inhaled drug aerosols reach predetermined lung sites, which are associated with specific diseases and/or treatments. Using the same human upper airway model, experimentally confirmed computer predictions of controlled particle transport from mouth to generation 3 are provided.}, number={3}, journal={JOURNAL OF AEROSOL MEDICINE-DEPOSITION CLEARANCE AND EFFECTS IN THE LUNG}, author={Kleinstreuer, Clement and Shi, Huawei and Zhang, Zhe}, year={2007}, pages={294–309} }
 @misc{kleinstreuer_li_farber_2007, title={Fluid-structure interaction analyses of stented abdominal aortic aneurysms}, volume={9}, DOI={10.1146/annurev.bioeng.9.060906.151853}, abstractNote={ Rupture of abdominal aortic aneurysms (AAAs) alone is the thirteenth leading cause of death in the United States. Thus, reliable AAA-rupture risk prediction is an important advancement. If repair becomes necessary, the minimally invasive technique of inserting a stent-graft (SG), commonly referred to as endovascular aneurysm repair (EVAR), is a viable option in many cases. However, postoperative complications, such as endoleaks and/or SG migration, may occur. Computational fluid-structure interaction simulations provide physical insight into the hemodynamics coupled with multi-wall mechanics’ function as an assessment tool for optimal SG placement and improved device design. }, journal={Annual Review of Biomedical Engineering}, author={Kleinstreuer, C. and Li, Z. and Farber, M. A.}, year={2007}, pages={169–204} }
 @article{shi_kleinstreuer_zhang_2007, title={Modeling of inertial particle transport and deposition in human nasal cavities with wall roughness}, volume={38}, ISSN={["1879-1964"]}, DOI={10.1016/j.jaerosci.2007.02.002}, abstractNote={Nasal inhalation helps to protect the lungs from detrimental effects of toxic particles which, however, may also place the nasal and adjacent tissues at risk. Alternatively, drug–aerosol deposition on pre-determined nasal airway surfaces can be a modern pathway for rapid medical treatment. The present study focuses on inertial particles in the range of 1μm⩽dp⩽50μm, subject to steady laminar flow rates of 7.5 and 20 L/min. In contrast to ultrafine particles, for certain fine particle sizes deposition is strongly affected by wall roughness, which was incorporated with a selective micro-size airway-surface layer. The validated computer simulation results show that the inertial particle deposition in human nasal cavities increases with increasing impaction parameter, IP=da2·Q. Most of the deposition occurs in the anterior part of the human nasal cavities, especially in the nasal valve region. Considering drug–aerosol targeting, an optimal impaction parameter value exists which generates for normal inlet conditions the largest deposition in desired areas, e.g., the middle meatus, inferior meatus and olfactory regions. However, the absolute deposition efficiencies, especially in the inferior meatus and olfactory region, are very small because particles hardly reach those regions due to the complex nasal geometric structures. The influence of gravity was also analyzed and an experimentally validated correlation for inertial particle deposition in human nasal cavities has been provided.}, number={4}, journal={JOURNAL OF AEROSOL SCIENCE}, author={Shi, Huawei and Kleinstreuer, Clement and Zhang, Zhe}, year={2007}, month={Apr}, pages={398–419} }
 @article{li_kleinstreuer_zhang_2007, title={Particle deposition in the human tracheobronchial airways due to transient inspiratory flow patterns}, volume={38}, ISSN={["1879-1964"]}, DOI={10.1016/j.jaerosci.2007.03.010}, abstractNote={Considering realistic tracheobronchial airways, transient airflow structures and micro-particle deposition patterns were simulated with an in-house finite-volume code for typical inhalation waveforms and Stokes numbers, i.e., the average flow rates at the trachea inlet, Qin,av, are 15 and 60L/min and the mean Stokes number at the trachea inlet, Stmean,trachea, is in the range of 0.0229⩽Stmean,trachea⩽0.0915, respectively. While the overall airflow fields exhibit similar characteristics, the local flow patterns which influence particle deposition are largely affected by secondary flows (for both Qin,av=15 and 60L/min) as well as airflow turbulence (when Qin,av=60L/min). The particle deposition fraction is a strongly transient function according to a given inhalation waveform. In light of the importance of targeted drug-aerosol delivery, it is shown that the relation between particle-release positions at the trachea inlet and particle depositions at specific lung sites are greatly influenced by the complex airway geometry and the flow-rate magnitude. For laminar flow, the particle-release points are deterministic and unique, as required for optimal drug-aerosol targeting.}, number={6}, journal={JOURNAL OF AEROSOL SCIENCE}, author={Li, Zheng and Kleinstreuer, Clement and Zhang, Zhe}, year={2007}, month={Jun}, pages={625–644} }
 @article{shi_kleinstreuer_2007, title={Simulation and analysis of high-speed droplet spray dynamics}, volume={129}, ISSN={["1528-901X"]}, DOI={10.1115/1.2717621}, abstractNote={Abstract}, number={5}, journal={JOURNAL OF FLUIDS ENGINEERING-TRANSACTIONS OF THE ASME}, author={Shi, H. and Kleinstreuer, C.}, year={2007}, month={May}, pages={621–633} }
 @article{li_kleinstreuer_zhang_2007, title={Simulation of airflow fields and microparticle deposition in realistic human lung airway models. Part I: Airflow patterns}, volume={26}, ISSN={["1873-7390"]}, DOI={10.1016/j.euromechflu.2007.02.003}, abstractNote={In Part I, transient and steady laminar airflow fields were simulated with an in-house finite volume code for realistic upper airway models subject to different inlet conditions and geometric features. Axial velocities and secondary flows were compared at key time levels during the acceleration/deceleration phase of inhaled air and for steady-state inhalation. The main results can be summarized as follows. Considering two acceleration and deceleration time levels during transient inhalation as well as steady-state inhalation generating the same inlet Reynolds number, Rein-mean=1201, the airflow patterns are quite similar. However, stronger axial and secondary velocities occur at all upper branch locations during flow deceleration because of the dynamic lingering effect. In general, the axial velocity profiles at steady state are very close to those at the point of deceleration. Variations in upper airway geometry, e.g., in-plane vs. out-of-plane configurations, have a significant effect on the airflow fields, although the primary airflow structures are similar in both idealized and more realistic airway configurations. The type of velocity inlet condition and existence of cartilaginous rings also influence the flow field; however, their impact is less important than changes in spatial angles.}, number={5}, journal={EUROPEAN JOURNAL OF MECHANICS B-FLUIDS}, author={Li, Zheng and Kleinstreuer, Clement and Zhang, Zhe}, year={2007}, pages={632–649} }
 @article{li_kleinstreuer_zhang_2007, title={Simulation of airflow fields and microparticle deposition in realistic human lung airway models. Part II: Particle transport and deposition}, volume={26}, ISSN={["1873-7390"]}, DOI={10.1016/j.euromechflu.2007.02.004}, abstractNote={In Part II, given the airflow fields discussed in Part I, microparticle deposition for a practical range of Stokes numbers, 0.025⩽St⩽0.102, has been simulated and analyzed, comparing different temporal assumptions, inlet conditions and geometric configurations. The matching steady-state assumption with equivalent Reynolds and Stokes numbers achieves basically the same deposition fraction (DF) values as under transient inhalation conditions. When comparing parabolic vs. realistic inlet velocity profiles, total DF-values are higher for the parabolic inlet flow for all Stokes numbers. Geometric features, such as out-of-plane configurations and cartilaginous rings in the trachea, further change local deposited microparticle concentrations when compared with simple airway models. Furthermore, significant differences were recorded when comparing DFs in some branches of the present realistic model and the Weibel Type A model. For practical purposes, algebraic microparticle-deposition correlations, DF=DF(Re,St), have been obtained for both the left and right upper lung airways. Based on current research results, the out-of-plane model with tracheal rings and realistic inlet condition is recommended for future work.}, number={5}, journal={EUROPEAN JOURNAL OF MECHANICS B-FLUIDS}, author={Li, Zheng and Kleinstreuer, Clement and Zhang, Zhe}, year={2007}, pages={650–668} }
 @article{li_kleinstreuer_2006, title={Analysis of biomechanical factors affecting stent-graft migration in an abdominal aortic aneurysm model}, volume={39}, ISSN={["1873-2380"]}, DOI={10.1016/j.jbiomech.2005.07.010}, abstractNote={Focusing on a representative abdominal aortic aneurysm (AAA) with a bifurcating stent-graft (SG), a fluid–structure interaction (FSI) solver with user-supplied programs has been employed to solve for blood flow, AAA/SG deformation, sac pressure and wall stresses, as well as the downward forces acting on the SG. Simulation results indicate that implanting a SG can significantly reduce sac pressure, mechanical stress, pulsatile wall motion, and maximum diameter change in AAAs; hence, it may restore normal blood flow and prevent AAA rupture effectively. The transient SG drag force is similar in trend as the cardiac pressure. Its magnitude depends on multi-factors including blood flow conditions, as well as SG and aneurysm geometries. Specifically, AAA neck angle, iliac bifurcation angle, neck aorta-to-iliac diameter ratio, SG size, and blood waveform play important roles in generating a fluid flow force potentially leading to SG migration. It was found that the drag force can exceed 5 N for an AAA with a large neck or iliac angle, wide aortic neck and narrow iliac arteries, large SG size, and/or abnormal blood waveform. Thus, the fixation of self-expandable or balloon-expandable SG contact may be inadequate to withstand the forces of blood flowing through the implant and hence means of extra fixation should be considered. A comprehensive FSI analysis of the coupled SG–AAA dynamics provides physical insight for evaluating the luminal hemodynamics, and maximum AAA-stresses as well as biomechanical factors leading potentially to SG migration.}, number={12}, journal={JOURNAL OF BIOMECHANICS}, author={Li, Z. and Kleinstreuer, C.}, year={2006}, pages={2264–2273} }
 @article{li_kleinstreuer_2006, title={Computational analysis of type II endoleaks in a stented abdominal aortic aneurysm model}, volume={39}, ISSN={["1873-2380"]}, DOI={10.1016/j.jbiomech.2005.09.002}, abstractNote={Insertion of a stent-graft into an aneurysm to form a new (synthetic) blood vessel and prevent the weakened artery wall from rupture is an attractive surgical intervention when compared to traditional open surgery. However, focusing on a stented abdominal aortic aneurysm (AAA), post-operative complications such as endoleaks may occur. An endoleak is the net influx of blood during the cardiac cycle into the cavity (or sac) formed by the stent-graft and the AAA wall. A natural endoleak source may stem from one or two secondary branches leading to and from the aneurysm, labeled types IIa and IIb endoleaks. Employing experimentally validated fluid-structure interaction solvers, the transient 3-D lumen and cavity blood flows, wall movements, pressure variations, maximum wall stresses and migration forces were computed for types IIa and IIb endoleaks. Simulation results indicate that the sac pressure caused by these endoleaks depends largely on the inlet branch pressure, where the branch inlet pressure increases, the sac pressure may reach the systemic level and AAA-rupture is possible. The maximum wall stress is typically located near the anterior-distal side in this model, while the maximum stent-graft stress occurs near the bifurcating point, in both cases, due to local stress concentrations. The time-varying leakage rate depends on the pressure difference between AAA sac and inlet branch. In contrast, the stent-graft migration force is reduced by type II endoleaks because it greatly depends on the pressure difference between the stent-graft and the aneurysm cavity.}, number={14}, journal={JOURNAL OF BIOMECHANICS}, author={Li, Z. and Kleinstreuer, C.}, year={2006}, pages={2573–2582} }
 @article{li_kleinstreuer_2006, title={Effects of blood flow and vessel geometry on wall stress and rupture risk of abdominal aortic aneurysms}, volume={30}, ISSN={0309-1902 1464-522X}, url={http://dx.doi.org/10.1080/03091900500217406}, DOI={10.1080/03091900500217406}, abstractNote={Sudden rupture of abdominal aortic aneurysm (AAA), often without prior medical warning, is the 13th leading cause of mortality in the US. The local rupture is triggered when the elusive maximum local wall stress exceeds the patient's yield stress. Employing a validated fluid – structure interaction code, the coupled blood flow and AAA wall dynamics were simulated and analysed for two representative asymmetric AAAs with different neck angles and iliac bifurcations. It turned out that the AAA morphology plays an important role in wall deformation and stress distribution, and hence possible rupture. The neck angle substantially impacts flow fields. A large neck angle may cause strong irregular vortices in the AAA cavity and may influence the wall stress distribution remarkably. The rupture risk of lateral asymmetric AAAs is higher than for the anterior – posterior asymmetric types. The most likely rupture site is located near the anterior distal side for the anterior – posterior asymmetric AAA and the left distal side in the lateral asymmetric AAA.}, number={5}, journal={Journal of Medical Engineering & Technology}, publisher={Informa UK Limited}, author={Li, Z. and Kleinstreuer, C.}, year={2006}, month={Jan}, pages={283–297} }
 @article{li_kleinstreuer_2006, title={Effects of major endoleaks on a stented abdominal aortic aneurysm}, volume={128}, ISSN={["1528-8951"]}, DOI={10.1115/1.2132376}, abstractNote={Insertion of a stent-graft into an aneurysm, especially abdominal aortic aneurysms (AAAs), is a very attractive surgical intervention; however, it is not without major postoperative complications, such as endoleaks. An endoleak is the transient accumulation of blood in the AAA cavity, which is formed by the stent-graft and AAA walls. Of the four blood pathways, a type I endoleak constitutes the major one. Thus, focusing on both proximal and distal type I endoleaks, i.e., the minute net influx of blood past the attachment points of a stent-graft into the AAA cavity, the transient three-dimensional interactions between luminal blood flow, stent-graft wall, leakage flow, and AAA wall are computationally simulated. For different type I endoleak scenarios and inlet pressure wave forms, the impact of type I endoleaks on cavity pressure, wall stress, and stent-graft migration force is analyzed. The results indicate that both proximal type I-a and distal type I-b endoleaks may cause cavity pressures close to a patient’s systemic pressure; however, with reduced pulsatility. As a result, the AAA-wall stress is elevated up to the level of a nonstented AAA and, hence, such endoleaks render the implant useless in protecting the AAA from possible rupture. Interestingly enough, the net downward force acting on the implant is significantly reduced; thus, in the presence of endoleaks, the risk of stent-graft migration may be mitigated.}, number={1}, journal={JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME}, author={Li, Z and Kleinstreuer, C}, year={2006}, month={Feb}, pages={59–68} }
 @article{zhang_kleinstreuer_kim_2006, title={Isotonic and hypertonic saline droplet deposition in a human upper airway model}, volume={19}, ISSN={["0894-2684"]}, DOI={10.1089/jam.2006.19.184}, abstractNote={The evaporative and hygroscopic effects and deposition of isotonic and hypertonic saline droplets have been simulated from the mouth to the first four generations of the tracheobronchial tree under laminar-transitional-turbulent inspiratory flow conditions. Specifically, the local water vapor transport, droplet evaporation rate, and deposition fractions are analyzed. The effects of inhalation flow rates, thermodynamic air properties and NaCl-droplet concentrations of interest are discussed as well. The validated computer simulation results indicate that the increase of NaCl-solute concentration, increase of inlet relative humidity, or decrease of inlet air temperature may reduce water evaporation and increase water condensation at saline droplet surfaces, resulting in higher droplet depositions due to the increasing particle diameter and density. However, solute concentrations below 10% may not have a very pronounced effect on droplet deposition in the human upper airways.}, number={2}, journal={JOURNAL OF AEROSOL MEDICINE-DEPOSITION CLEARANCE AND EFFECTS IN THE LUNG}, author={Zhang, Zhe and Kleinstreuer, Clement and Kim, Chong S.}, year={2006}, pages={184–198} }
 @article{shi_kleinstreuer_zhang_2006, title={Laminar airflow and nanoparticle or vapor deposition in a human nasal cavity model}, volume={128}, ISSN={["1528-8951"]}, DOI={10.1115/1.2244574}, abstractNote={The transport and deposition of nanoparticles, i.e., dp=1–2nm, or equivalent vapors, in the human nasal cavities is of interest to engineers, scientists, air-pollution regulators, and healthcare officials alike. Tiny ultrafine particles, i.e., dp≤5nm, are of special interest because they are most rapidly absorbed and hence have an elevated toxic or therapeutic impact when compared to larger particles. Assuming transient laminar 3-D incompressible flow in a representative human nasal cavity, the cyclic airflow pattern as well as local and overall nanoparticle depositions were computationally simulated and analyzed. The focus was on transient effects during inhalation/exhalation as compared to the steady-state assumption typically invoked. Then, an equation for a matching steady-state inhalation flow rate was developed that generates the same deposition results as cyclic inhalation. Of special interest is the olfactory region where the narrow channel surfaces receive only about one-half of a percent of the inhaled nanoparticles because the airflow bypasses these recesses located in the superior-most portions in the geometrically complex nasal cavities.}, number={5}, journal={JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME}, author={Shi, H. and Kleinstreuer, C. and Zhang, Z.}, year={2006}, month={Oct}, pages={697–706} }
 @article{zhang_kleinstreuer_kim_2006, title={Transport and uptake of MTBE and ethanol vapors in a human upper airway model}, volume={18}, ISSN={["1091-7691"]}, DOI={10.1080/08958370500434172}, abstractNote={Potential human exposure to vapors of methyl tertiary-butyl ether (MTBE) and ethanol is of increasing concern because these materials are widely used as gasoline additives. In this study we analyzed numerically the transport and deposition of MTBE and ethanol vapors in a model of the human upper respiratory airway, consisting of an oral airway and the first four generations of the tracheobronchial tree. Airflow characteristics and mass transfer processes were analyzed at different inspiratory flow conditions using a three-dimensional computational fluid and particle dynamics method. The deposition data were analyzed in terms of regional deposition fractions (DF = regional uptake/mouth concentration) and deposition enhancement factors (DEF = local DF/average DF) at local micro surface areas. Results show that DF in the entire upper airway model is 21.9%, 12.4%, and 6.9% for MTBE and 67.5%, 51.5%, and 38.5% for ethanol at a flow rate of 15, 30, and 60 L/min, respectively. Of the total DF, 65–70% is deposited in the oral airway for both vapors. Deposition is localized at various sites within the upper airway structure, with a maximum DEF of 1.5 for MTBE and 7.8 for ethanol. Local deposition patterns did not change with inhalation conditions, but DF and the maximum DEF increased with diffusivity, solubility, and the degree of airway wall absorption of vapors, as shown by a greater deposition of ethanol than MTBE. The vapor deposition efficiency as expressed by the dimensionless mass transfer coefficient correlated well with a product of Reynolds (Re) and Schmidt (Sc) numbers. In conclusion, MTBE and ethanol vapors deposit substantially in the upper airway structure with a marked enhancement of dose at local sites, and the deposition dose may be reasonably estimated by a functional relationship with dimensionless fluid flow and diffusion parameters.}, number={3}, journal={INHALATION TOXICOLOGY}, author={Zhang, Z and Kleinstreuer, C and Kim, CS}, year={2006}, month={Mar}, pages={169–184} }
 @article{zhang_kleinstreuer_kim_2006, title={Water vapor transport and its effects on the deposition of hygroscopic droplets in a human upper airway model}, volume={40}, ISSN={["1521-7388"]}, DOI={10.1080/02786820500461154}, abstractNote={The fundamentals of 3-D airflow as well as heat and water vapor transport and droplet vaporization (or hygroscopicity) are described for a human upper airway model under steady laminar-transitional-turbulent inspiratory flow conditions. Water vapor distributions from the mouth to the first four generations of the tracheobronchial tree are given in terms of relative humidity or mass fraction. The mass transfer coefficients of water vapor are correlated as a function of local flow rate and temperature-dependent diffusivity, which can be readily used for estimating the regional water loss or moisture variations in the human upper airways. Furthermore, the dynamics of hygroscopicity and deposition of isotonic saline droplets have been simulated as an example, applying the basic theory. Specifically, droplet evaporation rates and deposition pattern are analyzed and the effects of inhalation flow rates and thermodynamic air properties are discussed.}, number={1}, journal={AEROSOL SCIENCE AND TECHNOLOGY}, author={Zhang, Z and Kleinstreuer, C and Kim, CS}, year={2006}, month={Jan}, pages={1–16} }
 @article{li_kleinstreuer_2005, title={A new wall stress equation for aneurysm-rupture prediction}, volume={33}, ISSN={["1573-9686"]}, DOI={10.1007/s10439-005-8979-2}, abstractNote={Aneurysms, especially in the abdominal aorta (AAA), are prone to rupture, and hence a reliable and easy-to-use predictor is most desirable. Based on clinical observations and numerical analyses, a semi-empirical equation for the peak AAA-wall stress has been developed. It can be readily used for AAA-rupture predictions or can be integrated into more elaborate AAA-assessment models.}, number={2}, journal={ANNALS OF BIOMEDICAL ENGINEERING}, author={Li, Z and Kleinstreuer, C}, year={2005}, month={Feb}, pages={209–213} }
 @article{koo_kleinstreuer_2005, title={Analysis of surface roughness effects on heat transfer in micro-conduits}, volume={48}, ISSN={["1879-2189"]}, DOI={10.1016/j.ijheatmasstransfer.2005.01.024}, abstractNote={Modern heat rejection systems, such as micro-heat sinks, are attractive because of their potential for high performance at small size and low weight. However, the impact of microscale effects on heat transfer have to be considered and quantitatively analyzed in order to gain physical insight and accurate Nusselt number data. The relative surface roughness (SR) was selected as a key microscale parameter, represented by a porous medium layer (PML) model. Assuming steady laminar fully developed liquid flow in microchannels and microtubes, the SR effects in terms of PML thermal conductivity ratio and Darcy number on the dimemsionless temperature profile and Nusselt number were analyzed. In summary, the PML characteristics, especially the SR-number and conductivity ratio km/kf, greatly affect the heat transfer performance where the Nusselt number can be either higher or lower than the conventional value. The PML influence is less pronounced in microtubes than in parallel-plate microchannels.}, number={13}, journal={INTERNATIONAL JOURNAL OF HEAT AND MASS TRANSFER}, author={Koo, J and Kleinstreuer, C}, year={2005}, month={Jun}, pages={2625–2634} }
 @article{li_kleinstreuer_2005, title={Blood flow and structure interactions in a stented abdominal aortic aneurysm model}, volume={27}, ISSN={["1873-4030"]}, DOI={10.1016/j.medengphy.2004.12.003}, abstractNote={Since the introduction of endovascular techniques in the early 1990s for the treatment of abdominal aortic aneurysms (AAAs), the insertion of an endovascular graft (EVG) into the affected artery segment has been greatly successful for a certain group of AAA patients and is continuously evolving. However, although minimally invasive endovascular aneurysm repair (EVAR) is very attractive, post-operative complications may occur. Typically, they are the result of excessive fluid–structure interaction dynamics, possibly leading to EVG migration. Considering a 3D stented AAA, a coupled fluid flow and solid mechanics solver was employed to simulate and analyze the interactive dynamics, i.e., pulsatile blood flow in the EVG lumen, pressure levels in the stagnant blood filling the AAA cavity, as well as stresses and displacements in the EVG and AAA walls. The validated numerical results show that a securely placed EVG shields the diseased AAA wall from the pulsatile blood pressure and hence keeps the maximum wall stress 20 times below the wall stress value in the non-stented AAA. The sac pressure is reduced significantly but remains non-zero and transient, caused by the complex fluid–structure interactions between luminal blood flow, EVG wall, stagnant sac blood, and aneurysm wall. The time-varying drag force on the EVG exerted by physiological blood flow is unavoidable, where for patients with severe hypertension the risk of EVG migration is very high.}, number={5}, journal={MEDICAL ENGINEERING & PHYSICS}, author={Li, ZH and Kleinstreuer, C}, year={2005}, month={Jun}, pages={369–382} }
 @article{zhang_kleinstreuer_donohue_kim_2005, title={Comparison of micro- and nano-size particle depositions in a human upper airway model}, volume={36}, ISSN={["1879-1964"]}, DOI={10.1016/j.jaerosci.2004.08.006}, abstractNote={Simulation results of microparticle and nanoparticle deposition patterns, local concentrations, and segmental averages are contrasted for a human upper airway model starting from the mouth to planar airway generation G3 under different inspiratory flow conditions. Specifically, using a commercial finite-volume software with user-supplied programs as a solver, the Euler–Euler (nanoparticles) or the Euler–Lagrange (microparticles) approach was employed with a low-Reynolds-number k–ω model for laminar-to-turbulent airflow and submodels for particle-phase randomization. The results show that depositions of both micro- and nano-size particles vary measurably in the human upper airways; however, the deposition distributions are much more uniform for nanoparticles. The maximum deposition enhancement factor, which is defined as the ratio of local to average deposition concentrations, ranges from about 40 to 2400 for microparticles and about 2 to 11 for nanoparticles with inspiratory flow rates in the range of 15⩽Qin⩽60 l/min. In addition, some airway bifurcations in generations G0 to G3 subjected to high inlet flow rates (say, Qin=60l/min) may receive only very small amounts of large micro-size particles (say, with aerodynamic diameter dae⩾10μm) due to largely preferred upstream deposition. It has been hypothesized that, uniformly deposited nanoparticles of similar concentrations may have greater toxicity effects when compared to microparticles of the same material.}, number={2}, journal={JOURNAL OF AEROSOL SCIENCE}, author={Zhang, Z and Kleinstreuer, C and Donohue, JF and Kim, CS}, year={2005}, month={Feb}, pages={211–233} }
 @article{li_kleinstreuer_farber_2005, title={Computational analysis of biomechanical contributors to endovascular graft failure}, volume={4}, ISSN={["1617-7940"]}, DOI={10.1007/s10237-005-0003-0}, abstractNote={This paper evaluates numerically coupled blood flow and wall structure interactions in a representative stented abdominal aortic aneurysm (AAA) model, leading potentially to endovascular graft (EVG) failure. A total of 12 biomechanical contributors to possible EVG migration were considered. The results show that after EVG insertion for the given model, the peak AAA sac-pressure was reduced to 14.2 mmHg (11.8% of p(lumen)), and hence the maximum von Mises wall stress and wall deformation dropped by factors of 20 and 10, respectively. Thus, an EVG can significantly reduce sac pressure, mechanical stress, pulsatile wall motion, and the maximum diameter in AAAs and hence prevent AAA rupture effectively. In the absence of endoleaks, elevated sac-pressure can still be caused by fluid-structure interactions between the EVG, stagnant blood, and AAA wall. EVG migration forces vary from 1.4 to 7 N for different EVG geometries, material properties, and hemodynamic conditions. AAA-neck angle, iliac bifurcation angle, neck aorta-to-iliac diameter ratio, EVG size, aorto-uni-iliac EVG, and hypertension play important roles in generating forces potentially leading to EVG migration.}, number={4}, journal={BIOMECHANICS AND MODELING IN MECHANOBIOLOGY}, author={Li, Z and Kleinstreuer, C and Farber, M}, year={2005}, month={Dec}, pages={221–234} }
 @article{longest_kleinstreuer_2005, title={Computational models for simulating multicomponent aerosol evaporation in the upper respiratory airways}, volume={39}, ISSN={["0278-6826"]}, DOI={10.1080/027868290908786}, abstractNote={An effective model for predicting multicomponent aerosol evaporation in the upper respiratory system that is capable of estimating the vaporization of individual components is needed for accurate dosimetry and toxicology analyses. In this study, the performance of evaporation models for multicomponent droplets over a range of volatilities is evaluated based on comparisons to available experimental results for conditions similar to aerosols in the upper respiratory tract. Models considered include a semiempirical correlation approach as well as resolved-volume computational simulations of single and multicomponent aerosol evaporations to test the effects of variable gas-phase properties, surface blowing velocity, and internal droplet temperature gradients. Of the parameters assessed, concentration-dependent gas-phase specific heat had the largest effect on evaporation and should be taken into consideration for respiratory aerosols that contain high volatility species, such as n-heptane, at significant concentrations. For heavier droplet components or conditions below body temperatures, semiempirical estimates were shown to be appropriate for respiratory aerosol conditions. In order to reduce the number of equations and properties required for complex mixtures, a resolved-volume evaporation model was used to identify a twelve-component surrogate representation of potentially toxic JP-8 fuel based on comparisons to experimentally reported droplet evaporation data. Due to the relatively slow evaporation rate of JP-8 aerosols, results indicate that a semiempirical evaporation model in conjunction with the identified surrogate mixture provide a computationally efficient method for computing droplet evaporation that can track individual toxic markers. However, semiempirical methodologies are in need of further development to effectively compute the evaporation of other higher volatility aerosols for which variable gas-phase specific heat does play a significant role.}, number={2}, journal={AEROSOL SCIENCE AND TECHNOLOGY}, author={Longest, PW and Kleinstreuer, C}, year={2005}, month={Feb}, pages={124–138} }
 @article{li_kleinstreuer_2005, title={Fluid-structure interaction effects on sac-blood pressure and wall stress in a stented aneurysm}, volume={127}, ISSN={["1528-8951"]}, DOI={10.1115/1.1934040}, abstractNote={Abstract}, number={4}, journal={JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME}, author={Li, Z and Kleinstreuer, C}, year={2005}, month={Aug}, pages={662–671} }
 @article{koo_kleinstreuer_2005, title={Laminar nanofluid flow in microheat-sinks}, volume={48}, DOI={10.1016/j.ijheattransfer.2005.01.029}, number={13}, journal={International Journal of Heat and Mass Transfer}, author={Koo, J. M. and Kleinstreuer, C.}, year={2005}, pages={2652–2661} }
 @article{longest_kleinstreuer_deanda_2005, title={Numerical simulation of wall shear stress and particle-based hemodynamic parameters in pre-cuffed and streamlined end-to-side anastomoses}, volume={33}, ISSN={["1573-9686"]}, DOI={10.1007/s10439-005-7784-2}, abstractNote={A number of research studies have related multiple hemodynamic parameters to the formation of distal anastomotic intimal hyperplasia (IH) at the sub-cellular, cellular, and tissue levels. Focusing on mitigating WSS-based parameters alone, several studies have suggested geometrically modified end-to-side anastomoses with the intent of improving synthetic graft patency rates. However, recent clinical trials of commercially available versions of these grafts indicate persistently high rates of failure. Furthermore, recent evidence suggests that platelet-wall interactions may play a significant role in the formation of IH, which is not captured by WSS-based parameters alone. In this study, numerical simulations have been conducted to assess the potential for IH formation in conventional and geometrically modified anastomoses based on both wall shear stress (WSS) conditions and platelet-wall interactions. Sites of significant particle-wall interactions, including elevated concentrations and stasis, were identified by a near-wall residence time model, which includes factors for platelet activation and surface reactivity. Conventional, pre-cuffed, and streamlined distal end-to-side anastomoses were considered with proximal and distal arterial outflow. It was found that a pre-cuffed anastomosis, similar to the Distaflo configuration, does not offer a hemodynamic advantage over the conventional design considered with respect to the magnitude of the WSS field and the potential for platelet interactions with the vessel surface. Streamlined configurations largely consistent with venous confluences resulted in an advantageous reduction of wall shear stress gradient values; however, particle-wall interactions remained significant throughout the anastomosis. Results of this study are not intended to be directly extrapolated to surgical recommendations. However, these results highlight the difficulty associated with designing an end-to-side distal anastomosis with two-way outflow that is capable of simultaneously reducing multiple hemodynamic parameters. Further testing will be necessary to determine if the observed elevated particle-wall interactions in a pre-cuffed anastomosis provide the stimulus responsible for the reported high failure rates of these grafts.}, number={12}, journal={ANNALS OF BIOMEDICAL ENGINEERING}, author={Longest, PW and Kleinstreuer, C and Deanda, A}, year={2005}, month={Dec}, pages={1752–1766} }
 @article{koo_kleinstreuer_2004, title={A new thermal conductivity model for nanofluids}, volume={6}, ISSN={["1572-896X"]}, DOI={10.1007/s11051-004-3170-5}, number={6}, journal={JOURNAL OF NANOPARTICLE RESEARCH}, author={Koo, J and Kleinstreuer, C}, year={2004}, month={Dec}, pages={577–588} }
 @article{zhang_kleinstreuer_2004, title={Airflow structures and nano-particle deposition in a human upper airway model}, volume={198}, ISSN={["1090-2716"]}, DOI={10.1016/j.jcp.2003.11.034}, abstractNote={Considering a human upper airway model, or equivalently complex internal flow conduits, the transport and deposition of nano-particles in the 1–150 nm diameter range are simulated and analyzed for cyclic and steady flow conditions. Specifically, using a commercial finite-volume software with user-supplied programs as a solver, the Euler–Euler approach for the fluid-particle dynamics is employed with a low-Reynolds-number k–ω model for laminar-to-turbulent airflow and the mass transfer equation for dispersion of nano-particles or vapors. Presently, the upper respiratory system consists of two connected segments of a simplified human cast replica, i.e., the oral airways from the mouth to the trachea (Generation G0) and an upper tracheobronchial tree model of G0–G3. Experimentally validated computational fluid-particle dynamics results show the following: (i) transient effects in the oral airways appear most prominently during the decelerating phase of the inspiratory cycle; (ii) selecting matching flow rates, total deposition fractions of nano-size particles for cyclic inspiratory flow are not significantly different from those for steady flow; (iii) turbulent fluctuations which occur after the throat can persist downstream to at least Generation G3 at medium and high inspiratory flow rates (i.e., Qin⩾30 l/min) due to the enhancement of flow instabilities just upstream of the flow dividers; however, the effects of turbulent fluctuations on nano-particle deposition are quite minor in the human upper airways; (iv) deposition of nano-particles occurs to a relatively greater extent around the carinal ridges when compared to the straight tubular segments in the bronchial airways; (v) deposition distributions of nano-particles vary with airway segment, particle size, and inhalation flow rate, where the local deposition is more uniformly distributed for large-size particles (say, dp=100 nm) than for small-size particles (say, dp=1 nm); (vi) dilute 1 nm particle suspensions behave like certain (fuel) vapors which have the same diffusivities; and (vii) new correlations for particle deposition as a function of a diffusion parameter are most useful for global lung modeling.}, number={1}, journal={JOURNAL OF COMPUTATIONAL PHYSICS}, author={Zhang, Z and Kleinstreuer, C}, year={2004}, month={Jul}, pages={178–210} }
 @article{kleinstreuer_koo_2004, title={Computational analysis of wall roughness effects for liquid flow in micro-conduits}, volume={126}, number={1}, journal={Journal of Fluids Engineering}, author={Kleinstreuer, C. and Koo, J.}, year={2004}, month={Jan}, pages={09-} }
 @article{longest_kleinstreuer_buchanan_2004, title={Efficient computation of micro-particle dynamics including wall effects}, volume={33}, ISSN={["0045-7930"]}, DOI={10.1016/j.compfluid.2003.06.002}, abstractNote={This study describes an effective method for one-way coupled Eulerian–Lagrangian simulations of spherical micro-size particles, including particle–wall interactions and the quantification of near-wall stasis at possibly elevated concentrations. The focus is on particle-hemodynamics simulations where particle suspensions are composed of critical blood cells, such as monocytes, and the carrier fluid is non-Newtonian. Issues regarding adaptive time-step integration of the particle motion equation, relevant point-force model terms, and adaptation of surface-induced particle forces to arbitrary three-dimensional geometries are outlined. By comparison to available experimental trajectories, it is shown that fluid-element pathlines may be used to simulate non-interacting blood particles removed from wall boundaries under dilute transient conditions. However, when particle–wall interactions are significant, an extended form of the particle trajectory equation is required which includes terms for Stokes drag, near-wall drag modifications, or lubrication forces, pressure gradients, and near-wall particle lift. Still, additional physical and/or biochemical wall forces in the nano-meter range cannot be readily calculated; hence the near-wall residence time (NWRT) model indicating the probability of blood particle deposition is presented. The theory is applied to a virtual model of a femoral bypass end-to-side anastomosis, where profiles of the Lagrangian-based NWRT parameter are illustrated and convergence is verified. In order to effectively compute the large number of particle trajectories required to resolve regions of particle stasis, the proposed particle tracking algorithm stores all transient velocity field solution data on a shared memory architecture (SGI Origin 2400) and computes particle trajectories using an adaptive parallel approach. Compared to commercially available particle tracking packages, the algorithm presented is capable of reducing computational time by an order of magnitude for typical transient one-way coupled blood particle simulations in complex cyclical flow domains.}, number={4}, journal={COMPUTERS & FLUIDS}, author={Longest, PW and Kleinstreuer, C and Buchanan, JR}, year={2004}, month={May}, pages={577–601} }
 @article{longest_kleinstreuer_2004, title={Interacting effects of uniform flow, plane shear, and near-wall proximity on the heat and mass transfer of respiratory aerosols}, volume={47}, ISSN={["1879-2189"]}, DOI={10.1016/j.ijheatmasstransfer.2004.05.029}, abstractNote={Individual and interacting effects of uniform flow, plane shear, and near-wall proximity on spherical droplet heat and mass transfer have been assessed for low Reynolds number conditions beyond the creeping flow regime. Validated resolved volume simulations were used to compute heat and mass transfer surface gradients of two-dimensional axisymmetric droplets and three-dimensional spherical droplets near planar wall boundaries for conditions consistent with inhalable aerosols (5 ⩽ d ⩽ 300 μm) in the upper respiratory tract. Results indicate that planar shear significantly impacts droplet heat and mass transfer for shear-based Reynolds numbers greater than 1, which occur for near-wall respiratory aerosols with diameters in excess of 50 μm. Wall proximity is shown to significantly enhance heat and mass transfer due to conduction and diffusion at separation distances less than five particle diameters and for small Reynolds numbers. For the Reynolds number conditions of interest, significant non-linear effects arise due to the concurrent interaction of uniform flow and shear such that linear superposition of Sherwood or Nusselt number terms is not allowable. Based on the validated numeric simulations, multivariable Sherwood and Nusselt number correlations are provided to account for individual flow characteristics and concurrent non-linear interactions of uniform flow, planar shear, and near-wall proximity. These heat and mass transfer correlations can be applied to effectively compute condensation and evaporation rates of potentially toxic or therapeutic aerosols in the upper respiratory tract, where non-uniform flow and wall proximity are expected to significantly affect droplet transport, deposition, and vapor formation.}, number={22}, journal={INTERNATIONAL JOURNAL OF HEAT AND MASS TRANSFER}, author={Longest, PW and Kleinstreuer, C}, year={2004}, month={Oct}, pages={4745–4759} }
 @article{shi_kleinstreuer_zhang_kim_2004, title={Nanoparticle transport and deposition in bifurcating tubes with different inlet conditions}, volume={16}, ISSN={["1089-7666"]}, DOI={10.1063/1.1724830}, abstractNote={Transport and deposition of ultrafine particles in straight, bent and bifurcating tubes are considered for different inlet Reynolds numbers, velocity profiles, and particle sizes, i.e., 1 nm⩽dp⩽150 nm. A commercial finite-volume code with user-supplied programs was validated with analytical correlations and experimental data sets for nanoparticle depositions, considering a straight tube, a tubular 90° bend, and a G3-G5 double bifurcation with both planar and nonplanar configurations. The focus is on the airflow structures as well as nanoparticle deposition patterns and deposition efficiencies, which were analyzed for planar and nonplanar bifurcating lung airway models representing part of the upper bronchial tree. Deposition takes place primarily by Brownian diffusion, and thus deposition efficiencies increase with decreasing nanoparticle size and lower inlet Reynolds numbers. Deposition in the nonplanar configuration differs only slightly from that in the planar configuration. When compared with axisymmetric inlet conditions, the more realistic, skewed inlet velocity and particle profiles generate nearly axisymmetric deposition patterns as well. This work may elucidate basic physical insight of ultrafine particle transport and deposition relevant to environmental, industrial and biomedical studies.}, number={7}, journal={PHYSICS OF FLUIDS}, author={Shi, H and Kleinstreuer, C and Zhang, Z and Kim, CS}, year={2004}, month={Jul}, pages={2199–2213} }
 @article{hyun_kleinstreuer_longest_chen_2004, title={Particle-hemodynamics simulations and design options for surgical reconstruction of diseased carotid artery bifurcations}, volume={126}, ISSN={["1528-8951"]}, DOI={10.1115/1.1688777}, abstractNote={Based on the hypothesis that aggravating hemodynamic factors play a key role in the onset of arterial diseases, the methodology of “virtual prototyping” of branching blood vessels was applied to diseased external carotid artery (ECA) segments. The goals were to understand the underlying particle-hemodynamics and to provide various geometric design options for improved surgical reconstruction based on the minimization of critical hemodynamic wall parameters (HWPs). First, a representative carotid artery bifurcation (CAB) and then CABs with stenosed ECAs, i.e., a distally occluded ECA and an ECA stump, were analyzed based on transient three-dimensional blood flow solutions, employing a user-enhanced commercial finite volume code. Specifically, the HWPs, i.e., oscillatory shear index, wall shear stress angle gradient, near-wall residence time of monocytes, and near-wall helicity angle difference were evaluated to compare the merits of each design option, including a reconstructed near-optimal junction which generates the lowest HWP-values. The results provide physical insight to the biofluid dynamics of branching blood vessels and guide vascular surgeons as well as stent manufacturers towards interventions leading to high sustained patency rates.}, number={2}, journal={JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME}, author={Hyun, S and Kleinstreuer, C and Longest, PW and Chen, C}, year={2004}, month={Apr}, pages={188–195} }
 @article{zhang_kleinstreuer_kim_cheng_2004, title={Vaporizing Microdroplet Inhalation, Transport, and Deposition in a Human Upper Airway Model}, volume={38}, ISSN={0278-6826 1521-7388}, url={http://dx.doi.org/10.1080/02786820490247597}, DOI={10.1080/02786820300985}, abstractNote={Evaluation of injuries from inhalation exposure to toxic fuel requires detailed knowledge of inhaled aerosol transport and deposition in human airways. Focusing on highly toxic, easily volatized JP-8 fuel droplets, the three-dimensional airflow, temperature distributions, and fluid-particle thermodynamics, i.e., droplet motion as well as evaporation, are simulated and analyzed for laminar as well as locally turbulent flow conditions. Specifically, using a commercial finite-volume software with user-supplied programs as a solver, the Euler-Lagrange approach for the fluid-particle thermodynamics is employed with: (1) a low Reynolds number k-ω model for laminar-to-turbulent airflow, and (2) a stochastic model for random fluctuations in the droplet trajectories with droplet evaporation. Presently, the respiratory system consists of two major segments of a simplified human cast replica, i.e., a representative oral airway from mouth to trachea (Generation 0) and a symmetric four-generation upper bronchial tree model (G0 to G3). Experimentally validated computational fluid-particle thermodynamics results show that evaporation of JP-8 fuel droplets is greatly affecting deposition in the human airway. Specifically, droplet deposition fractions due to vaporization decrease with increasing ambient temperatures and decreasing inspiratory flow rates. It is also demonstrated that assuming idealized velocity profiles and particle distributions in or after the trachea may greatly overpredict particle deposition efficiencies in the upper bronchial tree.}, number={1}, journal={Aerosol Science and Technology}, publisher={Informa UK Limited}, author={Zhang, Zhe and Kleinstreuer, Clement and Kim, Chong S. and Cheng, Yung S.}, year={2004}, month={Jan}, pages={36–49} }
 @article{zhang_kleinstreuer_kim_cheng_2004, title={Vaporizing microdroplet inhalation, transport, and deposition in a human upper airway model}, volume={38}, ISSN={["1521-7388"]}, DOI={10.1080/02786820490247597}, abstractNote={Evaluation of injuries from inhalation exposure to toxic fuel requires detailed knowledge of inhaled aerosol transport and deposition in human airways. Focusing on highly toxic, easily volatized JP-8 fuel droplets, the three-dimensional airflow, temperature distributions, and fluid-particle thermodynamics, i.e., droplet motion as well as evaporation, are simulated and analyzed for laminar as well as locally turbulent flow conditions. Specifically, using a commercial finite-volume software with user-supplied programs as a solver, the Euler-Lagrange approach for the fluid-particle thermodynamics is employed with: (1) a low Reynolds number k-ω model for laminar-to-turbulent airflow, and (2) a stochastic model for random fluctuations in the droplet trajectories with droplet evaporation. Presently, the respiratory system consists of two major segments of a simplified human cast replica, i.e., a representative oral airway from mouth to trachea (Generation 0) and a symmetric four-generation upper bronchial tree model (G0 to G3). Experimentally validated computational fluid-particle thermodynamics results show that evaporation of JP-8 fuel droplets is greatly affecting deposition in the human airway. Specifically, droplet deposition fractions due to vaporization decrease with increasing ambient temperatures and decreasing inspiratory flow rates. It is also demonstrated that assuming idealized velocity profiles and particle distributions in or after the trachea may greatly overpredict particle deposition efficiencies in the upper bronchial tree.}, number={1}, journal={AEROSOL SCIENCE AND TECHNOLOGY}, author={Zhang, Z and Kleinstreuer, C and Kim, CS and Cheng, YS}, year={2004}, month={Jan}, pages={36–49} }
 @article{koo_kleinstreuer_2004, title={Viscous dissipation effects in microtubes and microchannels}, volume={47}, ISSN={["1879-2189"]}, DOI={10.1016/j.ijheatmasstransfer.2004.02.017}, abstractNote={The effects of viscous dissipation on the temperature field and ultimately on the friction factor have been investigated using dimensional analysis and experimentally validated computer simulations. Three common working fluids, i.e., water, methanol and iso-propanol, in different conduit geometries were considered. It turns out that for microconduits, viscous dissipation is a strong function of the channel aspect ratio, Reynolds number, Eckert number, Prandtl number and conduit hydraulic diameter. Thus, ignoring viscous dissipation could affect accurate flow simulations and measurements in microconduits.}, number={14-16}, journal={INTERNATIONAL JOURNAL OF HEAT AND MASS TRANSFER}, author={Koo, J and Kleinstreuer, C}, year={2004}, month={Jul}, pages={3159–3169} }
 @article{longest_kleinstreuer_2003, title={Comparison of blood particle deposition models for non-parallel flow domains}, volume={36}, ISSN={["1873-2380"]}, DOI={10.1016/S0021-9290(02)00434-7}, abstractNote={Adhesions of monocytes and platelets to a vascular surface, particularly in regions of flow stagnation, recirculation, and reattachment, are a significant initial event in a broad spectrum of particle–wall interactions that significantly influence the formation of stenotic lesions and mural thrombi. A number of approximations are available for the simulation of both monocyte and platelet interactions with the vascular surface. For the simulation of blood particle adhesion, this study hypothesizes that: (a) the discrete element approach, which accounts for finite particle size and inertia, is advantageous in the context of non-parallel flow domains including stagnation, recirculation, and reattachment; and (b) the likelihood for particle deposition may be effectively approximated as being non-linearly proportional to local particle concentration, residence time, and wall proximity. Models such as wall shear stress correlations, the multicomponent mixture approach, and Lagrangian particle tracking with and without hydrodynamic particle–wall interactions were evaluated. Quantitative performance of the selected models was established by comparisons to available experimental data sets for non-parallel axisymmetric suspension flows of monocytes and platelets. Factors including the convective-diffusive transport of particles, finite particle size and inertia, as well as near-wall hydrodynamic interactions were found to significantly influence blood particle deposition. Of the models studied, the near-wall residence time approach was found to be a particularly effective indicator for the deposition of monocytes (r2=0.74) and platelets (r2=0.57), given that nano-scale physical and biochemical effects must be greatly approximated in computational simulations involving relatively large-scale geometries and complex flow fields.}, number={3}, journal={JOURNAL OF BIOMECHANICS}, author={Longest, PW and Kleinstreuer, C}, year={2003}, month={Mar}, pages={421–430} }
 @article{zhang_kleinstreuer_2003, title={Computational thermodynamics analysis of vaporizing fuel droplets in the human upper airways}, volume={46}, ISSN={["1340-8054"]}, DOI={10.1299/jsmeb.46.563}, abstractNote={The detailed knowledge of air flow structures as well as particle transport and deposition in the human lung for typical inhalation flow rates is an important precursor for dosimetry-and-health-effect studies of toxic particles as well as for targeted drug delivery of therapeutic aerosols. Focusing on highly toxic JP-8 fuel aerosols, 3-D airflow and fluid-particle thermodynamics in a human upper airway model starting from mouth to Generation G3 (G0 is the trachea) are simulated using a user-enhanced and experimentally validated finite-volume code. The temperature distributions and their effects on airflow structures, fuel vapor deposition and droplet motion/evaporation are discussed. The computational results show that the thermal effect on vapor deposition is minor, but it may greatly affect droplet deposition in human airways.}, number={4}, journal={JSME INTERNATIONAL JOURNAL SERIES B-FLUIDS AND THERMAL ENGINEERING}, author={Zhang, Z and Kleinstreuer, C}, year={2003}, month={Nov}, pages={563–571} }
 @article{buchanan_kleinstreuer_hyun_truskey_2003, title={Hemodynamics simulation and identification of susceptible sites of atherosclerotic lesion formation in a model abdominal aorta}, volume={36}, ISSN={["1873-2380"]}, DOI={10.1016/S0021-9290(03)00088-5}, abstractNote={Employing the rabbit's abdominal aorta as a suitable atherosclerotic model, transient three-dimensional blood flow simulations and monocyte deposition patterns were used to evaluate the following hypotheses: (i) simulation of monocyte transport through a model of the rabbit abdominal aorta yields cell deposition patterns similar to those seen in vivo, and (ii) those deposition patterns are correlated with hemodynamic wall parameters related to atherosclerosis. The deposition pattern traces a helical shape down the aorta with local elevation in monocyte adhesion around vessel branches. The cell deposition pattern was altered by an exercise waveform with fewer cells attaching in the upper abdominal aorta but more attaching around the renal orifices. Monocyte deposition was correlated with the wall shear stress gradient and the wall shear stress angle gradient. The wall stress gradient, the wall shear stress angle gradient and the normalized monocyte deposition fraction were correlated with the distribution of monocytes along the abdominal aorta and monocyte deposition is correlated with the measured distribution of monocytes around the major abdominal branches in the cholesterol-fed rabbit. These results suggest that the transport and deposition pattern of monocytes to arterial endothelium plays a significant role in the localization of lesions.}, number={8}, journal={JOURNAL OF BIOMECHANICS}, author={Buchanan, JR and Kleinstreuer, C and Hyun, S and Truskey, GA}, year={2003}, month={Aug}, pages={1185–1196} }
 @article{kleinstreuer_zhang_2003, title={Laminar-to-turbulent fluid-particle flows in a human airway model}, volume={29}, ISSN={["1879-3533"]}, DOI={10.1016/S0301-9322(02)00131-3}, abstractNote={As in many biomedical and industrial applications, gas–solid two-phase flow fields in a curved tube with local area constrictions may be laminar, transitional and/or turbulent depending upon the inlet flow rate and tube geometry. Assuming steady incompressible air flow and non-interacting spherical micron-particles, the laminar-to-turbulent suspension flow problem was solved for a human airway model using a commercial software with user-supplied pre- and post-processing programs. All flow regimes (500<Relocal<104) were captured with an low-Reynolds-number k–ω turbulence model. Considering different steady inspiratory flow rates (15⩽Q⩽60 l/min) and Stokes numbers, the three-dimensional simulation results show the following: The onset of turbulence after the constriction in the larynx can be clearly observed when the inspiratory flow rate changes from low-level breathing (Qin=15 l/min) to high-level breathing (Qin=60 l/min). The flow reattachment length in the trachea becomes shorter, the axial velocity profile becomes more blunt, and the secondary flow decays faster with the occurrence of transition to turbulence. Particles follow the basic relationship between airflow and particle motion very well at the lower inspiratory flow rate (Qin=15 l/min); however, particle motion seems to be random and disperse, i.e., influenced by flow fluctuations in case of high inspiratory flow (Qin=60 l/min). Turbulence can enhance particle deposition in the trachea near the larynx to some extent, but it is more likely to affect the deposition of smaller particles (say, St<0.06) throughout the airway at relatively high flow rates (Qin=30 and 60 l/min) due to turbulent dispersion. However, the particle size and inhalation flow rate (i.e., Stokes number) are still the main factors influencing particle deposition when compared with turbulent dispersion alone. The methodology outlined can be readily applied to other two-phase flows undergoing changing flow regimes in complex tubular systems.}, number={2}, journal={INTERNATIONAL JOURNAL OF MULTIPHASE FLOW}, author={Kleinstreuer, C and Zhang, Z}, year={2003}, month={Feb}, pages={271–289} }
 @article{koo_kleinstreuer_2003, title={Liquid flow in microchannels: experimental observations and computational analyses of microfluidics effects}, volume={13}, ISSN={["1361-6439"]}, DOI={10.1088/0960-1317/13/5/307}, abstractNote={Experimental observations of liquid microchannel flows are reviewed and results of computer experiments concerning channel entrance, wall slip, non-Newtonian fluid, surface roughness, viscous dissipation and turbulence effects on the friction factor are discussed. The experimental findings are classified into three groups. Group I emphasizes ‘flow instabilities’ and group II points out ‘viscosity changes’ as the causes of deviations from the conventional flow theory for macrochannels. Group III caters to studies that did not detect any measurable differences between micro- and macroscale fluid flow behaviors. Based on numerical friction factor analyses, the entrance effect should be taken into account for any microfluidic system. It is a function of channel length, aspect ratio and the Reynolds number. Non-Newtonian fluid flow effects are expected to be important for polymeric liquids and particle suspension flows. The wall slip effect is negligible for liquid flows in microconduits. Significant surface roughness effects are a function of the Darcy number, the Reynolds number and cross-sectional configurations. For relatively low Reynolds numbers, Re < 2000, onset to turbulence has to be considered important because of possible geometric non-uniformities, e.g., a contraction and/or bend at the inlet to the microchannel. Channel-size effect on viscous dissipation turns out to be important for conduits with Dh < 100 µm.}, number={5}, journal={JOURNAL OF MICROMECHANICS AND MICROENGINEERING}, author={Koo, JM and Kleinstreuer, C}, year={2003}, month={Sep}, pages={568–579} }
 @article{zhang_kleinstreuer_2003, title={Low-Reynolds-number turbulent flows in locally constricted conduits: A comparison study}, volume={41}, ISSN={["0001-1452"]}, DOI={10.2514/2.2044}, abstractNote={In numerous internal flow systems the velocity field can undergo all flow regimes, that is, from laminar, via transitional, to fully turbulent. Considering two test conduits with local constrictions, four turbulence models, with an emphasis on low-Reynolds-number (LRN) turbulence models, were compared and evaluated. The objective was to identify a readily available LRN turbulence model with which incompressible laminar-to-turbulent velocity and pressure fields in complex three-dimensional conduits can be directly computed. The comparison study revealed that the renormalization group (RNG) κ-e and Menter κ-ω models amplify the flow instabilities after tubular constrictions and hence fail to capture the laminar flow behavior at low Reynolds numbers}, number={5}, journal={AIAA JOURNAL}, author={Zhang, Z and Kleinstreuer, C}, year={2003}, month={May}, pages={831–840} }
 @article{longest_kleinstreuer_2003, title={Numerical simulation of wall shear stress conditions and platelet localization in realistic end-to-side arterial anastomoses}, volume={125}, ISSN={["1528-8951"]}, DOI={10.1115/1.1613298}, abstractNote={Research studies over the last three decades have established that hemodynamic interactions with the vascular surface as well as surgical injury are inciting mechanisms capable of eliciting distal anastomotic intimal hyperplasia (IH) and ultimate bypass graft failure. While abnormal wall shear stress (WSS) conditions have been widely shown to affect vascular biology and arterial wall self-regulation, the near-wall localization of critical blood particles by convection and diffusion may also play a significant role in IH development. It is hypothesized that locations of elevated platelet interactions with reactive or activated vascular surfaces, due to injury or endothelial dysfunction, are highly susceptible to IH initialization and progression. In an effort to assess the potential role of platelet-wall interactions, experimentally validated particle-hemodynamic simulations have been conducted for two commonly implemented end-to-side anastomotic configurations, with and without proximal outflow. Specifically, sites of significant particle interactions with the vascular surface have been identified by a novel near-wall residence time (NWRT) model for platelets, which includes shear stress-based factors for platelet activation as well as endothelial cell expression of thrombogenic and anti-thrombogenic compounds. Results indicate that the composite NWRT model for platelet-wall interactions effectively captures a reported shift in significant IH formation from the arterial floor of a relatively high-angle (30 deg) graft with no proximal outflow to the graft hood of a low-angle graft (10 deg) with 20% proximal outflow. In contrast, other WSS-based hemodynamic parameters did not identify the observed system-dependent shift in IH formation. However, large variations in WSS-vector magnitude and direction, as encapsulated by the WSS-gradient and WSS-angle-gradient parameters, were consistently observed along the IH-prone suture-line region. Of the multiple hemodynamic factors capable of eliciting a hyperplastic response at the cellular level, results of this study indicate the potential significance of platelet-wall interactions coinciding with regions of low WSS in the development of IH.}, number={5}, journal={JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME}, author={Longest, PW and Kleinstreuer, C}, year={2003}, month={Oct}, pages={671–681} }
 @article{longest_kleinstreuer_archie_2003, title={Particle hemodynamics analysis of Miller cuff arterial anastomosis}, volume={38}, ISSN={["0741-5214"]}, DOI={10.1016/S0741-5214(03)00950-9}, abstractNote={Studies of animal and human below-knee anastomoses with Miller cuffs indicate that improved graft patency results from redistribution of intimal hyperplasia away from areas critical to flow delivery, such as the arterial toe. We hypothesize that particle hemodynamic conditions are a biophysical mechanism potentially responsible for the clinically observed shift in intimal hyperplasia localization associated with better patency of the Miller configuration.Computational fluid dynamics analysis of vortical flow patterns, wall shear stress fields, and potential for platelet interaction with the vascular surface was performed for realistic three-dimensional conventional and Miller cuff distal end-to-side anastomoses. Sites of significant platelet-wall interaction, including elevated near-wall particle concentrations and stasis, were identified with a validated near-wall residence time model, which includes shear stress-based factors for particle activation and surface reactivity.Particle hemodynamics largely coincide with the observed redistribution of intimal hyperplasia away from the critical arterial toe region. Detrimental changes in wall shear stress vector magnitude and direction are significantly reduced along the arterial suture line of the Miller cuff, largely as a result of increased anastomotic area available for flow redirection. However, because of strong particle-wall interaction, resulting high near-wall residence time contours indicate significant intimal hyperplasia along the graft-vein suture line and in the vicinity of the arterial heel.While a number of interacting mechanical, biophysical, and technical factors may be responsible for improved Miller cuff patency, our results imply that particle hemodynamics conditions engendered by Miller cuff geometry provide a mechanism that may account for redistribution of intimal hyperplasia. In particular, it appears that a focal region of significant particle-wall interaction at the arterial toe is substantially reduced with the Miller cuff configuration.}, number={6}, journal={JOURNAL OF VASCULAR SURGERY}, author={Longest, PW and Kleinstreuer, C and Archie, JP}, year={2003}, month={Dec}, pages={1353–1362} }
 @article{longest_kleinstreuer_2003, title={Particle-hemodynamics modeling of the distal end-to-side femoral bypass: effects of graft caliber and graft-end cut}, volume={25}, ISSN={["1873-4030"]}, DOI={10.1016/S1350-4533(03)00124-3}, abstractNote={Late-stage occlusions of peripheral synthetic bypass grafts are frequently due to intimal hyperplasia and/or thrombosis at the distal anastomosis, resulting in unacceptably high failure rates. It has been widely established that hemodynamic and blood particle interactions with the vascular surface as well as surgical injury and compliance mismatch are inciting mechanisms capable of eliciting various cellular level responses associated with distal anastomotic intimal hyperplasia (IH) formation. Primary geometric factors influencing anastomotic hemodynamics include the graft-to-artery diameter ratio and graft-hood shape, which are determined by the graft caliber and initial graft-end cut selected by the vascular surgeon. In this study, the particle-hemodynamic effects of graft-end cuts (straight, curved, and S-shaped) and graft-to-artery diameter ratios (2:1 vs. 1.5:1) have been numerically assessed in four common unexpanded anastomotic configurations with respect to vortical flow patterns, wall shear stress based parameters, and platelet interactions with the vascular surface. Sites of significant platelet–wall interactions have been identified by a novel near-wall residence time (NWRT) model, which includes shear stress based factors for platelet activation and endothelial cell expression of anti-thrombogenic compounds. Of the configurations evaluated, straight and curved graft-end cuts with a graft-to-artery diameter ratio of 1.5:1 were found to reduce the particle-hemodynamic potential for IH development at locations critical to flow delivery. Nevertheless, the potential for significant IH occurrence via platelet and/or endothelial response pathways was highly evident in all conventional anastomoses considered, such that a decisively superior configuration was not determined. These results illustrate the need for alternative anastomotic designs with the intent of reducing critical hemodynamic wall parameters and mitigating regions of significant particle–wall interactions.}, number={10}, journal={MEDICAL ENGINEERING & PHYSICS}, author={Longest, PW and Kleinstreuer, C}, year={2003}, month={Dec}, pages={843–858} }
 @article{longest_kleinstreuer_truskey_buchanan_2003, title={Relation between near-wall residence times of monocytes and early lesion growth in the rabbit aorto-celiac junction}, volume={31}, ISSN={["0090-6964"]}, DOI={10.1114/1.1531635}, abstractNote={Transient particle-hemodynamic simulations were conducted in a model of the rabbit aorto-celiac junction to investigate mechanisms responsible for localized monocyte attachment and subsequent lesion formation. We hypothesized that the probability for monocyte deposition is related to discrete near-wall particle stasis and/or elevated concentrations, as encapsulated by a new near-wall residence time (NWRT) parameter. A low wall shear stress (WSS) condition accounted for factors such as endothelial cell expression of adhesive molecules as well as a reduced probability of monocyte rolling and detachment. To accurately simulate particle transport, terms for the near-wall drag modification and lift were included. Low WSS and high oscillatory shear index parameters proved ineffective compared to localized in vivo results of monocyte accumulation and lesion initialization. The NWRT parameter, with a limiting WSS condition, identified the lateral flow divider as most susceptible to monocyte deposition, as observed in vivo. A representative quantitative correlation between monocyte deposition and NWRT occurrence was established (r2 = 0.77 and p<10(-4)) on a highly focal basis for an averaged data set. Results indicate that cell transport and conditions for hemodyamically induced surface reactivity are necessary components in formulating an effective model for monocyte adhesion in complex three-dimensional vessel configurations.}, number={1}, journal={ANNALS OF BIOMEDICAL ENGINEERING}, author={Longest, PW and Kleinstreuer, C and Truskey, GA and Buchanan, JR}, year={2003}, month={Jan}, pages={53–64} }
 @article{zhang_kleinstreuer_2003, title={Species heat and mass transfer in a human upper airway model}, volume={46}, ISSN={["1879-2189"]}, DOI={10.1016/S0017-9310(03)00358-2}, abstractNote={Steady 3-D airflow and scalar transport of ultrafine particles, dp<0.1 μm, and fuel vapors within the human upper airways are simulated and analyzed for laminar as well as locally turbulent flow conditions. Presently, our respiratory system consists of two major segments of a simplified human cast replica, i.e., a representative oral airway from mouth to trachea (Generation 0) and a symmetric four-generation upper bronchial tree model (G0–G3). The simulation has been validated with experimental data in terms of ultrafine particle deposition efficiencies. The present computational results show the following: (1) At low breathing rates (Qin≈15 l/min), ambient temperature variations (ΔTmax=47 °C) influence the local velocity fields and vapor concentrations; however, the total and segmental deposition fractions of fuel vapor in the upper airway are essentially unaffected. (2) The inlet flow rate has a significant effect on vapor deposition, i.e., the higher the flow rate the lower the deposition fraction. (3) The convective heat transfer coefficient averaged over an individual bifurcation unit can be correlated as Nu=0.568(RePr)0.495 (600 < Re < 6000). (4) Two new Sherwood number correlations capture the convective mass transfer for the oral airway and individual bifurcations. The methodology outlined and physical insight provided can be also applied to other intake configurations, such as engine ports and inlets to air-breathing propulsion systems.}, number={25}, journal={INTERNATIONAL JOURNAL OF HEAT AND MASS TRANSFER}, author={Zhang, Z and Kleinstreuer, C}, year={2003}, month={Dec}, pages={4755–4768} }
 @article{kleinstreuer_zhang_2003, title={Targeted drug aerosol deposition analysis for a four-generation lung airway model with hemispherical tumors}, volume={125}, ISSN={["1528-8951"]}, DOI={10.1115/1.1543548}, abstractNote={One important research area of broad interest is the development of highly efficient drug delivery systems for desired site deposition and uptake. For example, controlled drug aerosol release and targeting to specific regions of the lung is a novel way to combat lung diseases, diabetes, virus infections, cancers, etc. Determination of feasible air-particle streams is a prerequisite for the development of such delivery devices, say, smart inhalers. The concept of “controlled particle release and targeting” is introduced and results are discussed for a representative model of bronchial lung airways afflicted with hemispherical tumors of different sizes and locations. It is shown that under normal particle inlet conditions a particle mass fraction of only up to 11% may deposit on the surface of a specific tumor with critical radius r/R≈1.25, while a controlled particle release achieves deposition fractions of 35 to 92% for a realistic combination of inlet Stokes and Reynolds numbers, depending mainly on tumor size. Furthermore, with the controlled release and targeting approach nearby healthy tissue is hardly impacted by the typically aggressive drug aerosols. Assuming laminar, quasi-steady, three-dimensional air flow and spherical non-interacting micron-particles in sequentially bifurcating rigid airways, the results were obtained using a validated commercial finite-volume code with user-enhanced programs on a high-end engineering workstation. The new concept is generic and hence should be applicable to other regions of the respiratory system as well.}, number={2}, journal={JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME}, author={Kleinstreuer, C and Zhang, Z}, year={2003}, month={Apr}, pages={197–206} }
 @article{loh_hyun_ro_kleinstreuer_2002, title={Acoustic streaming induced by ultrasonic flexural vibrations and associated enhancement of convective heat transfer}, volume={111}, ISSN={["0001-4966"]}, DOI={10.1121/1.1433811}, abstractNote={Acoustic streaming induced by ultrasonic flexural vibrations and the associated convection enhancement are investigated. Acoustic streaming pattern, streaming velocity, and associated heat transfer characteristics are experimentally observed. Moreover, analytical analysis based on Nyborg’s formulation is performed along with computational fluid dynamics (CFD) simulation using a numerical solver CFX 4.3. Two distinctive acoustic streaming patterns in half-wavelength of the flexural vibrations are observed, which agree well with the theory. However, acoustic streaming velocities obtained from CFD simulation, based on the incompressible flow assumption, exceed the theoretically estimated velocity by a factor ranging from 10 to 100, depending upon the location along the beam. Both CFD simulation and analytical analysis reveal that the acoustic streaming velocity is proportional to the square of the vibration amplitude and the wavelength of the vibrating beam that decreases with the excitation frequency. It is observed that the streaming velocity decreases with the excitation frequency. Also, with an open-ended channel, a substantial increase in streaming velocity is observed from CFD simulations. Using acoustic streaming, a temperature drop of 40 °C with a vibration amplitude of 25 μm at 28.4 kHz is experimentally achieved.}, number={2}, journal={JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA}, author={Loh, BG and Hyun, S and Ro, PI and Kleinstreuer, C}, year={2002}, month={Feb}, pages={875–883} }
 @article{zhang_kleinstreuer_kim_2002, title={Aerosol deposition efficiencies and upstream release positions for different inhalation modes in an upper bronchial airway model}, volume={36}, ISSN={["1521-7388"]}, DOI={10.1080/02786820290092078}, abstractNote={Accurate predictions of micron-particle deposition patterns and surface concentrations in lung airways are most desirable for researchers assessing health effects of toxic particles or those concerned with inhalation delivery of therapeutic aerosols. Focusing on a rigid, symmetric triple bifurcation lung airway model, i.e., Weibel's generations G3-G6, a user-enhanced and experimentally validated finite volume program has been employed to simulate the airflow and particle transport under transient laminar three-dimensional flow conditions. Specifically, the effects of 3 inhalation modes, i.e., resting and light and moderate activities, were analyzed for typical ranges of Stokes numbers (St h 0.2) and Reynolds numbers (0 h Re h 2100). The detailed results show particle deposition patterns and efficiencies in the triple bifurcation under cyclic as well as steady-state inhalation conditions. Cyclic inhalation generates higher local and segmentally-averaged deposition rates when compared to steady mean Reynolds number inhalation; however, matching Stokes and Reynolds numbers, i.e., the average between mean and peak values, were found to provide fully equivalent results for all inhalation modes and bifurcations. In addition, particle maps were developed that show the release positions of deposited aerosols.}, number={7}, journal={AEROSOL SCIENCE AND TECHNOLOGY}, author={Zhang, Z and Kleinstreuer, C and Kim, CS}, year={2002}, month={Jul}, pages={828–844} }
 @article{zhang_kleinstreuer_kim_hickey_2002, title={Aerosol transport and deposition in a triple bifurcation bronchial airway model with local tumors}, volume={14}, ISSN={["1091-7691"]}, DOI={10.1080/08958370290084809}, abstractNote={Airflow characteristics and particle deposition have been numerically simulated in a triple bifurcation lung airway model (from generation 3-6 airways) with local tumors protruded from the sidewalls of generation 5 airways. The effects of tumors in terms of size and location on airflow, particle transport, and deposition patterns were analyzed for constant inspiratory flow rates with inlet Reynolds (Re match = 463 and 1882) and Stokes number (St match = 0.02-0.12) combinations that match different cyclic inhalation waveforms. The size of tumors was varied to induce an obstruction of airway lumen by 16-74%. Extreme conditions, 2 and 100% obstruction, were also examined. The results show that enhanced deposition occurs in the carina region at each bifurcation, and deposition increases with increasing Stokes and Reynolds number as expected from earlier studies. In addition, deposition increases at the tumor site until the tumor blocks about half of the airway lumen and then decreases with a further obstruction. In other words, there exists a maximum particle deposition fraction (DF) for a protruding tumor that occludes the lumen. The maximum DF at the tumor was 10.2% within the test conditions used. Deposition occurs mainly on the frontal surface of the tumors, but spreads out to the opposite wall, or upstream sections, or sister branches of the tumor at high flow rates and Stokes number. The present results (1) help in the understanding of the complex toxic or therapeutic aerosol dynamics in the lung with local airways obstruction, and (2) provide quantitative information on critical tumor size and particle deposition to health care specialists.}, number={11}, journal={INHALATION TOXICOLOGY}, author={Zhang, Z and Kleinstreuer, C and Kim, CS and Hickey, AJ}, year={2002}, month={Nov}, pages={1111–1133} }
 @article{zhang_kleinstreuer_kim_2002, title={Cyclic micron-size particle inhalation and deposition in a triple bifurcation lung airway model}, volume={33}, ISSN={["1879-1964"]}, DOI={10.1016/S0021-8502(01)00170-7}, abstractNote={Laminar oscillatory inhalation flow as well as micron-particle transport and wall deposition in a representative triple bifurcation airway model have been simulated using a commercial finite-volume code with user-enhanced programs. The computer model has been validated with experimental particle deposition data and deposition patterns for double bifurcations. The transient air flow, particle transport, and wall deposition patterns were analyzed and summarized in terms of particle deposition efficiencies (DEs) and surface density maps. Particle deposition may increase under cyclic flow conditions, i.e., DE-values are typically larger for cyclic flow than for steady flow at the mean flow rate of a given inhalation pulse. The maximal relative difference between these two DE-values may be as high as 50% for 0.02⩽Stmean⩽0.12 during normal inspiration (Qin=30l/min). However, matching inlet Reynolds and Stokes numbers are proposed, which generate under quasi-steady flow conditions very similar DE-values and deposition patterns as in equivalent pulsatile flow. The relative differences between DE-values for cyclic and matching steady cases are less than 5%. The quantitative results of this work are of interest to researchers either conducting health risk assessment studies for inhaled particulate pollutants or analyzing drug aerosol deposition at desired lung target sites.}, number={2}, journal={JOURNAL OF AEROSOL SCIENCE}, author={Zhang, Z and Kleinstreuer, C and Kim, CS}, year={2002}, month={Feb}, pages={257–281} }
 @article{zhang_kleinstreuer_kim_2002, title={Gas-solid two-phase flow in a triple bifurcation lung airway model}, volume={28}, ISSN={["1879-3533"]}, DOI={10.1016/S0301-9322(02)00011-3}, abstractNote={Laminar oscillatory flow as well as micron-particle transport and wall deposition in a triple bifurcation airway model have been simulated using a validated finite-volume code with user-enhanced programs. Three realistic breathing patterns, i.e., resting, light activity and moderate exercise, were considered. Transient air flow, particle transport, and wall deposition results are shown and summarized in terms of regional particle deposition efficiencies (DEs). The effects of skewed inlet profiles on the flow field and particle deposition were recorded as well. Particle deposition may increase under cyclic flow conditions, i.e., DE-values are typically larger for cyclic flow than for steady flow evaluated at the mean flow rate of a given inhalation or exhalation pulse. While particles deposit mainly around the carinal ridges, i.e., flow dividers, during inspiratory flow due to direct impaction, they deposit on the tubular surfaces during exhalation because of strong secondary flows. Moreover, particle deposition during exhalation is much lower than for inhalation at the same local Stokes number. The comparisons of DEs among different lung generations or bifurcation areas for both cyclic inhalation and exhalation show that DEs in the third bifurcation region may be quite different from those at previous bifurcations due to upstream geometry and flow effects.}, number={6}, journal={INTERNATIONAL JOURNAL OF MULTIPHASE FLOW}, author={Zhang, Z and Kleinstreuer, C and Kim, CS}, year={2002}, month={Jun}, pages={1021–1046} }
 @article{zhang_kleinstreuer_kim_2002, title={Micro-particle transport and deposition in a human oral airway model}, volume={33}, ISSN={["0021-8502"]}, DOI={10.1016/S0021-8502(02)00122-2}, abstractNote={Laminar-to-turbulent air flow for typical inhalation modes as well as micro-particle transport and wall deposition in a representative human oral airway model have been simulated using a commercial finite-volume code with user-enhanced programs. The computer model has been validated with experimental airflow and particle deposition data sets. For the first time, accurate local and segmentally averaged particle deposition fractions have been computed under transitional and turbulent flow conditions. Specifically, turbulence that occurs after the constriction in the oral airways for moderate and high-level breathing can enhance particle deposition in the trachea near the larynx, but it is more likely to affect the deposition of smaller particles, say, St<0.05. Particles released around the top/bottom zone of the inlet plane more easily deposit on the curved oral airway surface. Although more complicated geometric features of the oral airway may have a measurable effect on particle deposition, the present simulations with a relatively simple geometry exhibit the main features of laminar-transitional-turbulent particle suspension flows in actual human oral airways. Hence, the present model may serve as the “entryway” for simulating and analyzing airflow and particle deposition in the lung.}, number={12}, journal={JOURNAL OF AEROSOL SCIENCE}, author={Zhang, Z and Kleinstreuer, C and Kim, CS}, year={2002}, month={Dec}, pages={1635–1652} }
 @article{zhang_kleinstreuer_2002, title={Transient airflow structures and particle transport in a sequentially branching lung airway model}, volume={14}, DOI={10.1063/1.1433495}, abstractNote={Considering oscillatory laminar incompressible three-dimensional flow in triple planar and nonplanar bifurcations representing generations three to six of the human respiratory system, air flow fields and micron-particle transport have been simulated under normal breathing and high-frequency ventilation (HFV) conditions. A finite-volume code (CFX4.3 from AEA Technology, Pittsburgh, PA) and its user-enhanced FORTRAN programs were validated with experimental velocity data points for a single bifurcation. The airflow structures and micron-particle motion in the triple bifurcations were analyzed for a representative normal breathing cycle as well as HFV condition. While both the peak inspiratory and expiratory velocity profiles for the low Womersley case (α=0.93) agree well with those of instantaneously equivalent steady-state cases, some differences can be observed between flow acceleration and deceleration at off-peak periods or near flow reversal, especially during inspiratory flow. Similarly, the basic features of instantaneous particle motion closely resemble the steady-state case at equivalent inlet Reynolds numbers. The preferential concentration of particles caused by the coherent vortical structures was found in both inhalation and exhalation; however, it is more complicated during expiration. The effects of Womersley number and non-planar geometries as well as the variations in secondary flow intensity plus pressure drops across various bifurcations under normal breathing and HFV conditions were analyzed as well. This work may elucidate basic physical insight of aerosol transport relevant in dosimetry-and-health-effect studies as well as for drug aerosol delivery analyses.}, number={2}, journal={Physics of Fluids (Woodbury, N.Y.)}, author={Zhang, Z. and Kleinstreuer, C.}, year={2002}, pages={862–880} }
 @article{kleinstreuer_2001, title={'Effects of asymmetric branch flow rates on aerosol deposition in bifurcating airways', by Z. Zhang, C. Kleinstreuer and C. S. Kim - Response}, volume={25}, ISSN={["0309-1902"]}, DOI={10.1080/03091900110046952}, abstractNote={Selectively, Dr Martonen’s comments are correct in that anatomical elements such as the larynx, the large airways with protruding cartilaginous rings, and the carinal ridges may have locally signiŽ cant effects on  uid and particle motion, i.e. they are largely conŽned within and immediately downstream of the anatomic sites. For example, experimental studies have shown that despite very different velocity proŽ les at the inlet of the trachea (i.e. one with a larynx and another without a larynx), the axial velocity proŽ les are virtually identical in the main bronchi [1]. Thus, we believe that his comments have no relevance to our well-deŽ ned dual task, and they do not enhance the knowledge base of this particular Ž eld of research.}, number={3}, journal={JOURNAL OF MEDICAL ENGINEERING & TECHNOLOGY}, author={Kleinstreuer, C}, year={2001}, pages={127–127} }
 @article{longest_kleinstreuer_buchanan_2001, title={A New Near-wall Residence Time Model Applied to Three Arterio-venous Graft End-to-side Anastomoses}, volume={4}, ISSN={1025-5842 1476-8259}, url={http://dx.doi.org/10.1080/10255840108908015}, DOI={10.1080/10255840108908015}, abstractNote={As a representative example of an end-to-side anastomosis, the distal portion of an arterio-venous hemodialysis graft with three graft-end designs and two outflow conditions has been considered. Arterio-venous graft failure for hemodialysis patients can be frequently related to stenotic developments, especially in the toe region. With critical blood particles such as LDL, platelets, and monocytes, being considered as a first-order approximation of; blood elements pathlines, near-wall residence times and wall stagnation points have been simulated to identify, in conjunction with the wall shear stress gradient, susceptible sites of stenotic developments. Assuming transient laminar three-dimensional non-Newtonian fluid flow, the transport equations were solved with validated finite-volume based CFD software and user-Fortran programs for the computation of fluid element pathlines and hemodynamic parameters. We conclude from this study that for the application of looped arterio-venous grafts, the graft-end geometry and the presence of retrograde outflow significantly influence the magnitude and location of the hemodynamic wall parameters considered. The new concept of near-wall blood “particle” behaviour, in conjunction with a wall shear stress based hemodynamic parameter, can be compared to similar histopathologic studies of intimal hyperplasia formation to understand better the role of hemodynamic factors in the biogenesis of the disease.}, number={5}, journal={Computer Methods in Biomechanics and Biomedical Engineering}, publisher={Informa UK Limited}, author={Longest, P. W. and Kleinstreuer, C. and Buchanan, J. R.}, year={2001}, month={Jan}, pages={379–397} }
 @article{hyun_kleinstreuer_archie_2001, title={Computational particle-hemodynamics analysis and geometric reconstruction after carotid endarterectomy}, volume={31}, ISSN={["0010-4825"]}, DOI={10.1016/S0010-4825(01)00007-5}, abstractNote={Transient three-dimensional laminar incompressible dilute suspension flow in rigid in-plane carotid artery bifurcations has been solved with a user-enhanced finite-volume program. Instantaneous velocity vector and wall shear stress vector fields illustrate strong "disturbed flow" patterns. Implications of elevated surface contours of hemodynamic wall parameters, indicating such disturbed flows, and particle deposition sites are discussed and a relative comparison in terms of indicator functions between the endarterectomized carotid artery bifurcation and two design improvements is shown. Although the combined perioperative mortality and non-fatal stroke rate for carotid endarterectomy ranges only from 2% to 7%, the final geometric design recommendation presented merits consideration because it may significantly lower the chances of post-operative complications such as stroke, ischemic attack, or even death. The new carotid artery bifurcation design is based on the overall reduction of "disturbed flow" indicator functions, including the time-averaged wall shear stress angle deviation and a wall deposition parameter for critical blood particles, such as monocytes.}, number={5}, journal={COMPUTERS IN BIOLOGY AND MEDICINE}, author={Hyun, S and Kleinstreuer, C and Archie, JP}, year={2001}, month={Sep}, pages={365–384} }
 @article{zhang_kleinstreuer_2001, title={Effect of particle inlet distributions on deposition in a triple bifurcation lung airway model}, volume={14}, ISSN={["0894-2684"]}, DOI={10.1089/08942680152007864}, abstractNote={Considering a triple bifurcation as a representative lung airway model of the upper bronchial tree, the effect of different random inlet particle distributions on deposition patterns and efficiencies have been numerically analyzed. The steady laminar three-dimensional transport equations for a dilute micron-size particle suspension have been solved using a commercial finite-volume code with user-enhanced programs. Particle release positions were assigned employing a random number generator following random-parabolic, random-uniform, and random-random distribution functions. Via back tracking, starting positions of all depositing particles were determined for each particle release distribution, including a deterministic-parabolic one which served as a base case. The results indicate that: (1) The starting regions of the depositing particles in a given bifurcation are fixed for the same inlet Reynolds number and Stokes number combination, regardless of the type of distribution profile. The situation for the particle deposition patterns is somewhat similar. However, the type of distribution of inlet particles strongly influences the particle deposition efficiencies. (2) Values of particle deposition efficiencies are very close for the same (parabolically) distributed deterministic versus random inlet particles when all other conditions are fixed. (3) According to the simulation validations, a determinstic parabolic distribution of inlet particles may be sufficient for laboratory data comparison purposes, but random distributions should reflect realistic environmental or medical aerosol inhalation more accurately.}, number={1}, journal={JOURNAL OF AEROSOL MEDICINE-DEPOSITION CLEARANCE AND EFFECTS IN THE LUNG}, author={Zhang, Z and Kleinstreuer, C}, year={2001}, pages={13–29} }
 @article{zhang_kleinstreuer_kim_2001, title={Effects of curved inlet tubes on air flow and particle deposition in bifurcating lung models}, volume={34}, ISSN={["1873-2380"]}, DOI={10.1016/S0021-9290(00)00233-5}, abstractNote={In vivo bifurcating airways are complex and the airway segments leading to the bifurcations are not always straight, but curved to various degrees. How do such curved inlet tubes influence the motion as well as local deposition and hence the biological responses of inhaled particulate matter in lung airways? In this paper steady laminar dilute suspension flows of micron-particles are simulated in realistic double bifurcations with curved inlet tubes, i.e., 0 degrees < or =theta< or =90 degrees, using a commercial finite-volume code with user-enhanced programs. The resulting air-flow patterns as well as particle transport and wall depositions were analyzed for different flow inlet conditions, i.e., uniform and parabolic velocity profiles, and geometric configurations. The curved inlet segments have quite pronounced effects on air-flow, particle motion and wall deposition in the downstream bifurcating airways. In contrast to straight double bifurcations, those with bent parent tubes also exhibit irregular variations in particle deposition efficiencies as a function of Stokes number and Reynolds number. There are fewer particles deposited at mildly curved inlet segments, but the particle deposition efficiencies at the downstream sequential bifurcations vary much when compared to those with straight inlets. Under certain flow conditions in sharply curved lung airways, relatively high, localized particle depositions may take place. The findings provide necessary information for toxicologic or therapeutic impact assessments and for global lung dosimetry models of inhaled particulate matter.}, number={5}, journal={JOURNAL OF BIOMECHANICS}, author={Zhang, Z and Kleinstreuer, C and Kim, CS}, year={2001}, month={May}, pages={659–669} }
 @article{zhang_kleinstreuer_kim_2001, title={Flow structure and particle transport in a triple bifurcation airway model}, volume={123}, ISSN={["1528-901X"]}, DOI={10.1115/1.1359525}, abstractNote={Considering steady laminar incompressible flow in a triple bifurcation, which represents generations three to six of the human respiratory system, air flow fields and micron-particle transport have been simulated for several combinations of relatively high and low inlet Reynolds and Stokes numbers. While the upstream bifurcations are hardly affected by the third bifurcation, complex air and particle flow fields occur in the daughter tubes leading to the third dividers. Variations in Reynolds number, 500⩽Re⩽2000, and Stokes number, 0.04⩽St⩽0.12, cause locally changing vortical air flows as well as irregular particle motions. Preferential concentration of particles can be induced by the secondary vortical flow in the tubes when the inlet Reynolds number is high enough. The air and particle velocity profiles in the third daughter tubes are still quite different from those in the upstream tubes, which indicates that additional downstream effects are possible. This work may contribute to respiratory dose estimation in health risk assessment studies, as well as the analyses of drug aerosol delivery.}, number={2}, journal={JOURNAL OF FLUIDS ENGINEERING-TRANSACTIONS OF THE ASME}, author={Zhang, Z and Kleinstreuer, C and Kim, CS}, year={2001}, month={Jun}, pages={320–330} }
 @article{comer_kleinstreuer_zhang_2001, title={Flow structures and particle deposition patterns in double-bifurcation airway models. Part 1. Air flow fields}, volume={435}, ISSN={["1469-7645"]}, DOI={10.1017/s0022112001003809}, abstractNote={The understanding and quantitative assessment of air flow fields and local micron-particle wall concentrations in tracheobronchial airways are very important for estimating 
the health risks of inhaled particulate pollutants, developing algebraic transfer 
functions of global lung deposition models used in dose-response analyses, and/or 
determining proper drug-aerosol delivery to target sites in the lung. In this paper (Part 
1) the theory, model geometries, and air flow results are provided. In a companion 
paper (Part 2, Comer et al. 2001), the history of particle deposition patterns and 
comparisons with measured data sets are reported. Decoupling of the naturally dilute 
particle suspension makes it feasible to present the results in two parts.}, journal={JOURNAL OF FLUID MECHANICS}, author={Comer, JK and Kleinstreuer, C and Zhang, Z}, year={2001}, month={May}, pages={25–54} }
 @article{comer_kleinstreuer_kim_2001, title={Flow structures and particle deposition patterns in double-bifurcation airway models. Part 2. Aerosol transport and deposition}, volume={435}, ISSN={["1469-7645"]}, DOI={10.1017/s0022112001003810}, abstractNote={The flow theory and air flow structures in symmetric double-bifurcation airway models 
assuming steady laminar, incompressible flow, unaffected by the presence of aerosols, 
has been described in a companion paper (Part 1). The validated computer simulation 
results showed highly vortical flow fields, especially around the second bifurcations, 
indicating potentially complex particle distributions and deposition patterns. In this 
paper (Part 2), assuming spherical non-interacting aerosols that stick to the wall 
when touching the surface, the history of depositing particles is described. Specifically, 
the finite-volume code CFX (AEA Technology) with user-enhanced FORTRAN 
programs were validated with experimental data of particle deposition efficiencies 
as a function of the Stokes number for planar single and double bifurcations. The 
resulting deposition patterns, particle distributions, trajectories and time evolution 
were analysed in the light of the air flow structures for relatively low 
(ReD1 = 500) and high (ReD1 = 2000) 
Reynolds numbers and representative Stokes numbers, i.e. StD1 = 0.04 and 
StD1 = 0.12. Particle deposition patterns and surface concentrations 
are largely a function of the local Stokes number, but they also depend on the 
fluid–particle inlet conditions as well as airway geometry factors. While particles 
introduced at low inlet Reynolds numbers (e.g. ReD1 = 500) 
follow the axial air flow, secondary and vortical flows become important at higher Reynolds numbers, causing 
the formation of particle-free zones near the tube centres and subsequently elevated 
particle concentrations near the walls. Sharp or mildly rounded carinal ridges have 
little effect on the deposition efficiencies but may influence local deposition patterns. 
In contrast, more drastic geometric changes to the basic double-bifurcation model, 
e.g. the 90°-non-planar configuration, alter both the aerosol wall distributions and 
surface concentrations considerably.}, journal={JOURNAL OF FLUID MECHANICS}, author={Comer, JK and Kleinstreuer, C and Kim, CS}, year={2001}, month={May}, pages={55–80} }
 @article{kleinstreuer_hyun_buchanan_longest_archie_truskey_2001, title={Hemodynamic parameters and early intimal thickening in branching blood vessels}, volume={29}, DOI={10.1615/critrevbiomedeng.v29.i1.10}, abstractNote={Intimal thickening due to atherosclerotic lesions or intimal hyperplasia in medium to large blood vessels is a major contributor to heart disease, the leading cause of death in the Western World. Balloon angioplasty with stenting, bypass surgery, and endarterectomy (with or without patch reconstruction) are some of the techniques currently applied to occluded blood vessels. On the basis of the preponderance of clinical evidence that disturbed flow patterns play a key role in the onset and progression of atherosclerosis and intimal hyperplasia, it is of interest to analyze suitable hemodynamic wall parameters that indicate susceptible sites of intimal thickening and/or favorable conditions for thrombi formation. These parameters, based on the wall shear stress, wall pressure, or particle deposition, are applied to interpret experimental/clinical observations of intimal thickening. Utilizing the parameters as "indicator" functions, internal branching blood vessel geometries are analyzed and possibly altered for different purposes: early detection of possibly highly stenosed vessel segments, prediction of future disease progression, and vessel redesign to potentially improve long-term patency rates. At the present time, the focus is on the identification of susceptible sites in branching blood vessels and their subsequent redesign, employing hemodynamic wall parameters. Specifically, the time-averaged wall shear stress (WSS), its spatial gradient (WSSG), the oscillatory shear index (OSI), and the wall shear stress angle gradient (WSSAG) are compared with experimental data for an aortoceliac junction. Then, the OSI, wall particle density (WPD), and WSSAG are segmentally averaged for different carotid artery bifurcations and compared with clinical data of intimal thickening. The third branching blood vessel under consideration is the graft-to-vein anastomosis of a vascular access graft. Suggested redesigns reduce several hemodynamic parameters (i.e., the WSSG, WSSAG, and normal pressure gradient [NPG]), thereby reducing the likelihood of restenosis, especially near the critical toe region.}, number={1}, journal={Critical Reviews in Biomedical Engineering}, author={Kleinstreuer, C. and Hyun, S. and Buchanan, J. R. and Longest, P. W. and Archie, J. P. and Truskey, G. A.}, year={2001}, pages={1–64} }
 @article{hyun_kleinstreuer_2001, title={Numerical simulation of mixed convection heat and mass transfer in a human inhalation test chamber}, volume={44}, ISSN={["1879-2189"]}, DOI={10.1016/S0017-9310(00)00268-4}, abstractNote={Large baffled rectangular chambers, Rochester-style test chambers, and displacement ventilated rooms have traditionally been used to study effects of potentially toxic pollutants on animals and humans. Recently, the interest in harmful effects of indoor gaseous pollutants and associated air quality control have rapidly increased because most urban dwellers spend more than 90% of their daily lives in closed environments. Of interest here are the experimentally validated CFD simulations of transient turbulent non-isothermal flow with tracer gas transport in a personal exposure environment. The purpose of this paper is to examine the effect of transient breathing on trace gas ambient (i.e., exposure) concentrations and ultimately the uptake (i.e., dose concentrations) by the subject for three different orientations with respect to the non-isothermal air stream and the location of the tracer gas source.}, number={12}, journal={INTERNATIONAL JOURNAL OF HEAT AND MASS TRANSFER}, author={Hyun, S and Kleinstreuer, C}, year={2001}, month={Jun}, pages={2247–2260} }
 @article{comer_kleinstreuer_hyun_kim_2000, title={Aerosol transport and deposition in sequentially bifurcating airways}, volume={122}, ISSN={["1528-8951"]}, DOI={10.1115/1.429636}, abstractNote={Deposition patterns and efficiencies of a dilute suspension of inhaled particles in three-dimensional double bifurcating airway models for both in-plane and 90 deg out-of-plane configurations have been numerically simulated assuming steady, laminar, constant-property air flow with symmetry about the first bifurcation. Particle diameters of 3, 5, and 7 μm were used in the simulation, while the inlet Stokes and Reynolds numbers varied from 0.037 to 0.23 and 500 to 2000, respectively. Comparisons between these results and experimental data based on the same geometric configuration showed good agreement. The overall trend of the particle deposition efficiency, i.e., an exponential increase with Stokes number, was somewhat similar for all bifurcations. However, the deposition efficiency of the first bifurcation was always larger than that of the second bifurcation, while in general the particle efficiency of the out-of-plane configuration was larger than that of the in-plane configuration. The local deposition patterns consistently showed that the majority of the deposition occurred in the carinal region. The distribution pattern in the first bifurcation for both configurations were symmetric about the carina, which was a direct result of the uniaxial flow at the inlet. The deposition patterns about the second carina showed increased asymmetry due to highly nonuniform flow generated by the first bifurcation and were extremely sensitive to bifurcation orientation. Based on the deposition variations between bifurcation levels and orientations, the use of single bifurcation models was determined to be inadequate to resolve the complex fluid–particle interactions that occur in multigenerational airways. [S0148-0731(00)01102-X]}, number={2}, journal={JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME}, author={Comer, JK and Kleinstreuer, C and Hyun, S and Kim, CS}, year={2000}, month={Apr}, pages={152–158} }
 @article{longest_kleinstreuer_andreotti_2000, title={Computational analyses and design improvements of graft-to-vein anastomoses}, volume={28}, ISSN={["0278-940X"]}, DOI={10.1615/critrevbiomedeng.v28.i12.240}, abstractNote={For hemodialysis patients, arteriovenous grafts are omnipresent. Unfortunately, a large percentage of such grafts fail within the first year after surgery because of occlusive lesions mainly at the venous anastomotic site. It is textbook knowledge that critical values of certain hemodynamic parameters, such as low (oscillatory) wall shear stresses, large sustained wall shear stress gradients, significant changes in wall shear stress angles, excessive radial pressure gradients, etc., play significant roles in the onset and/or development of vascular diseases. The idea is to geometrically design graft-to-vein configurations such that aggravating flow patterns are reduced, and hence stenotic developments are minimized. Focusing on a new blood rheological model in conjunction with three graft-to-vein anastomotic configurations, that is, a base case, the Bard-IMPRA Venaflo graft, and a new graft-end design, the corresponding transient laminar 3-D hemodynamics are numerically simulated and compared. The design criterion for the best performance of these junction geometries is the most significant reduction in locally disturbed flow as expressed by equally weighted indicator functions for the onset and progression of stenotic developments. As a result of this comparison study, quantitative recommendations for arteriovenous loop graft designs toward increased patency rates are provided. The resulting improved graft design will be scrutinized in clinical trials.}, number={1-2}, journal={CRITICAL REVIEWS IN BIOMEDICAL ENGINEERING}, author={Longest, PW and Kleinstreuer, C and Andreotti, PJ}, year={2000}, pages={141–147} }
 @article{longest_kleinstreuer_2000, title={Computational haemodynamics analysis and comparison study of arterio-venous grafts}, volume={24}, number={3}, journal={Journal of Medical Engineering & Technology}, author={Longest, P. W. and Kleinstreuer, C.}, year={2000}, month={May}, pages={102–110} }
 @article{hyun_kleinstreuer_archie_2000, title={Computer simulation and geometric design of endarterectomized carotid artery bifurcations}, volume={28}, ISSN={["0278-940X"]}, DOI={10.1615/critrevbiomedeng.v28.i12.100}, abstractNote={The main goal of this computational study is to establish surgical guidelines for optimal geometries of carotid endarterectomy reconstructions that may measurably reduce postoperative complications, that is, thrombosis, stroke, and/or restenosis. The underlying hypotheses are that nonuniform hemodynamics, or "disturbed flows," are linked to arterial diseases and consequently that minimization of "disturbed flow" indicators leads to geometric bifurcation designs that lower postoperative complication rates. Considering transient 3-D laminar blood flow in partially occluded, in-plane, rigid-wall carotid artery bifurcations, the results presented include time-averaged indicators of "disturbed flow", such as the wall shear stress, spatial wall shear stress gradient, and wall shear stress angle deviation. In addition, trajectories and deposition patterns of critical blood particles (i.e., monocytes) are shown and evaluated. Within given physiological constraints, the vessel geometry was then changed in order to reduce the magnitudes of key indicators associated with thrombosis (i.e., blood clot formation) or restenosis (e.g., renewed atherosclerosis and/or hyperplasia). The quantitative results and knowledge base generated will be crucial for future clinical trials.}, number={1-2}, journal={CRITICAL REVIEWS IN BIOMEDICAL ENGINEERING}, author={Hyun, S and Kleinstreuer, C and Archie, JP}, year={2000}, pages={53–59} }
 @article{zhang_kleinstreuer_kim_2000, title={Effects of asymmetric branch flow rates on aerosol deposition in bifurcating airways}, volume={24}, number={5}, journal={Journal of Medical Engineering & Technology}, author={Zhang, Z. and Kleinstreuer, C. and Kim, C. S.}, year={2000}, month={Sep}, pages={192–202} }
 @article{hyun_kleinstreuer_archie_2000, title={Hemodynamics analyses of arterial expansions with implications to thrombosis and restenosis}, volume={22}, ISSN={["1350-4533"]}, DOI={10.1016/S1350-4533(00)00006-0}, abstractNote={It is assumed that critical hemodynamic factors play an important role in the onset, localization and degree of post-operative complications, for example, thrombosis and restenosis. Of special interest are sudden expansion flows, which may occur in straight artery segments such as the common carotid after endarterectomy or end-to-end anastomoses. Sudden expansion geometries are possible origins of early post-operative emboli and significant myointimal hyperplasia resulting in early or late complications. Transient laminar axisymmetric and fully three-dimensional blood flows were simulated employing a validated finite volume code in conjunction with a Runge–Kutta particle tracking technique. Disturbed flow indicators, which may predict the onset of thrombosis and/or restenosis, were identified and employed to evaluate 90°-step and smooth expansion geometries. Smooth expansion geometries have weaker disturbed flow features than step expansion geometries. Specifically, the regions near the expansion wall and the reattachment point are susceptible to both atherosclerotic lesion and thrombi formations as indicated by non-uniform hemodynamic indicators such as near-zero wall shear stress and elevated wall shear stress gradients as well as blood particle accumulation and deposition. A new parameter, the wall shear stress angle deviation (WSSAD) has been introduced, which indicates areas of abnormal endothelial cell morphology and particle wall deposition. In turn, regions of low wall shear stress and high wall shear stress gradients are recognized as susceptible sites for arterial diseases. Thus, it is interesting to note that high WSSAD surface areas cover low wall shear stress, high wall shear stress gradient locations as well as high wall particle deposition. A gradual change in step expansion geometry provides better results in terms of WSSAD values and hence potentially reducing atherosclerosis as well as thrombi formation.}, number={1}, journal={MEDICAL ENGINEERING & PHYSICS}, author={Hyun, S and Kleinstreuer, C and Archie, JP}, year={2000}, month={Jan}, pages={13–27} }
 @article{buchanan_kleinstreuer_comer_2000, title={Rheological effects on pulsatile hemodynamics in a stenosed tube}, volume={29}, ISSN={["0045-7930"]}, DOI={10.1016/S0045-7930(99)00019-5}, abstractNote={Transient laminar axisymmetric flow through a tube with a smooth local area reduction of 75% is considered. Using an experimentally validated control volume method, the influence of three rheology models (i.e., Newtonian, power law and Quemada) are investigated. Three Womersley numbers (Wo=r0ω/ν1/2:=4.0, 7.5 and 12.5) are compared for a sinusoidal input pulse which varies between 0 and 400 with a mean Reynolds number of 200. The primary application is pulsatile flow in axisymmetric stenosed artery segments. Results show that for the highest Womersley number considered here, a second co-rotating vortex is formed distal to the primary vortex. Also, the shear-thinning rheological models have a secondary effect on the flow field that primarily appears in terms of subtle changes to the hemodynamic wall parameters (i.e., the time-averaged wall shear stress, spatial wall shear stress gradient, and oscillatory shear index). The non-Newtonian models affect the entrainment of fluid-like particles in the post-stenotic region measurably. The particle residence time (PRT), defined as the ratio of transient to steady residence times, is found to be less than or equal to unity for the majority of fluid elements for all rheologies and Womersley numbers considered. The highest fraction of PRT < 1 is found at moderate Womersley numbers. Pathological fluid elements, where PRT > 10, is found to increase with increasing Wo and is decreased by the non-Newtonian formulations. This is due to a low-shear high-viscosity band that impedes the progress of fluid particles into the near wall region.}, number={6}, journal={COMPUTERS & FLUIDS}, author={Buchanan, JR and Kleinstreuer, C and Comer, JK}, year={2000}, month={Jul}, pages={695–724} }
 @article{longest_kleinstreuer_kinsey_2000, title={Turbulent three-dimensional air flow and trace gas distribution in an inhalation test chamber}, volume={122}, ISSN={["0098-2202"]}, DOI={10.1115/1.483270}, abstractNote={Steady incompressible turbulent air flow and transient carbon monoxide transport in an empty Rochester-style human exposure chamber have been numerically simulated and compared with experimental data sets. The system consisted of an inlet duct with a continuous carbon monoxide point source, 45- and 90-degree bends, a round diffuser, a round-to-square transition, a rectangular diffuser, the test chamber, a perforated floor, and again transition pieces from the chamber to an outlet duct. Such a configuration induced highly nonuniform vortical flow patterns in the chamber test area where a pollutant concentration is required to be constant at breathing level for safe and accurate inhalation studies. Presented are validated momentum and mass transfer results for this large-scale system with the main goals of determining the development of tracer gas (CO) distributions in the chamber and analyzing the contributions to CO-mixing. Numerical simulations were conducted employing a k-ε model and the latest available RNG k-ε model for air and CO-mixing. Both models predict similar velocity fields and are in good agreement with measured steady and transient CO-concentrations. It was found that secondary flows in the inlet section and strong vortical flow in the chamber with perforated flooring contributed to effective mixing of the trace gas at breathing levels. Specifically, in the height range of 1.4 m<h<2.0 m above the chamber floor, predicted CO-concentrations rapidly reached a near constant value which agrees well with experimental results. This work can be extended to analyze trace gas mixing as well as aerosol dispersion in occupied test chambers with or without flow redirection devices installed in the upstream section. A complementary application is particle transport and deposition in clean rooms of the electronic, pharmaceutical, and health care industries. [S0098-2202(00)01702-8]}, number={2}, journal={JOURNAL OF FLUIDS ENGINEERING-TRANSACTIONS OF THE ASME}, author={Longest, PW and Kleinstreuer, C and Kinsey, JS}, year={2000}, month={Jun}, pages={403–411} }
 @article{buchanan_kleinstreuer_truskey_lei_1999, title={Relation between non-uniform hemodynamics and sites of altered permeability and lesion growth at the rabbit aorto-celiac junction}, volume={143}, ISSN={["1879-1484"]}, DOI={10.1016/S0021-9150(98)00264-0}, abstractNote={Using the rabbit's aorto-celiac junction as a representative atherosclerotic model, the hemodynamics of a bifurcating blood vessel are numerically simulated and three hemodynamic parameters are compared. The wall shear stress (WSS), the oscillatory shear index (OSI), and the spatial wall shear stress gradient (WSSG) are considered in this study. Locally enhanced wall permeabilities and intimal macrophages are generally considered to be involved in atherogenesis, and here the primary concern is with the hemodynamic influence on these early stages of the disease process. In comparing the segmental averages of the indicator functions and previously published intimal white blood cell densities, only the WSSG shows a statistically significant correlation. All three indicators have selective strengths in determining sites of early lesion growth around the aorto-celiac flow divider. At the proximal end of the flow divider on the lateral side of the orifice, there are elevated values of the OSI as well as WSSG and low WSS values. Regions of elevated wall permeabilities compare with the regions of elevated WSSG along the lateral and distal portions of the flow divider. Largely dependent upon the present input pulse with reverse flow, the OSI indicates relatively high values throughout the flow domain, however, it is important when utilized in conjunction with low WSS regions. This study presents a rationale for further quantitative correlative studies in the rabbit model based on additional histological data sets.}, number={1}, journal={ATHEROSCLEROSIS}, author={Buchanan, JR and Kleinstreuer, C and Truskey, GA and Lei, M}, year={1999}, month={Mar}, pages={27–40} }
 @article{buchanan_kleinstreuer_longest_1998, title={Analytical solution to flux enhancement in laminar concentrically stratified pipe flow of Bingham and Newtonian fluids}, volume={120}, ISSN={["0098-2202"]}, DOI={10.1115/1.2820711}, abstractNote={Technical Briefs Analytical Solution to Flux Enhancement in Laminar Concentrically Stratified Pipe Flow of Bingham and Newtonian Fluids C. D. Buchanan, C. D. Buchanan Department of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, NC 27695-7910 Search for other works by this author on: This Site PubMed Google Scholar C. Kleinstreuer, C. Kleinstreuer Department of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, NC 27695-7910 Search for other works by this author on: This Site PubMed Google Scholar P. W. Longest P. W. Longest Department of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, NC 27695-7910 Search for other works by this author on: This Site PubMed Google Scholar Author and Article Information C. D. Buchanan Department of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, NC 27695-7910 C. Kleinstreuer Department of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, NC 27695-7910 P. W. Longest Department of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, NC 27695-7910 J. Fluids Eng. Sep 1998, 120(3): 629-631 (3 pages) https://doi.org/10.1115/1.2820711 Published Online: September 1, 1998 Article history Received: August 21, 1997 Revised: February 24, 1998 Online: January 22, 2008}, number={3}, journal={JOURNAL OF FLUIDS ENGINEERING-TRANSACTIONS OF THE ASME}, author={Buchanan, CD and Kleinstreuer, C and Longest, PW}, year={1998}, month={Sep}, pages={629–631} }
 @article{buchanan_kleinstreuer_1998, title={Simulation of particle-hemodynamics in a partially occluded artery segment with implications to the initiation of microemboli and secondary stenoses}, volume={120}, ISSN={["1528-8951"]}, DOI={10.1115/1.2798013}, abstractNote={Computational results of laminar incompressible blood-particle flow analyses in an axisymmetric artery segment with a smooth local area constriction of 75 percent have been presented. The flow input waveform was sinusoidal with a nonzero average. The non-Newtonian behavior of blood was simulated with a modified Quemada model, platelet concentrations were calculated with a drift-flux model, and monocyte trajectories were described and compared for both Newtonian and Quemada rheologies. Indicators of “disturbed flow” included the time-averaged wall shear stress (WSS), the oscillatory shear index (OSI), and the wall shear stress gradient (WSSG). Implications of the vortical flow patterns behind the primary stenosis to the formation of microemboli and downstream stenoses are as follows. Elevated platelet concentrations due to accumulation in recirculation zones mixed with thrombin and ADP complexes assumed to be released upstream in high wall shear stress regions, could form microemboli, which are convected downstream. Distinct near-wall vortices causing a local increase in the WSSG and OSI as well as blood-particle entrainment with possible wall deposition, indicate sites susceptible to the onset of an additional stenosis proximal to the initial geometric disturbance.}, number={4}, journal={JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME}, author={Buchanan, JR and Kleinstreuer, C}, year={1998}, month={Aug}, pages={446–454} }
 @article{lei_archie_kleinstreuer_1997, title={Computational design of a bypass graft that minimizes wall shear stress gradients in the region of the distal anastomosis}, volume={25}, ISSN={["0741-5214"]}, DOI={10.1016/S0741-5214(97)70289-1}, abstractNote={Recent experimental and theoretic studies show that large wall shear stress gradients characterize disturbed flow patterns associated with the location of myointimal hyperplasia, atheroma, or both. Graft-to-artery anastomoses that minimize wall shear stress gradients may reduce the degree of myointimal development and the propensity for thrombosis. This study analyzes the distribution of distal anastomotic wall shear stress gradients for conventional geometries and for the optimized geometry assuming idealized merging of the graft with the artery.A validated computational fluid dynamics program was used to solve the transient three-dimensional partial differential equations and auxiliary equations that describe laminar incompressible blood flow. Time-averaged wall shear stresses and wall shear stress gradients were calculated for three distal graft-artery anastomoses: a standard end-to-side, a Taylor patch, and an optimized geometry. The latter was obtained iteratively by minimizing the local wall shear stress gradients and was analyzed under resting and exercise inflow waveforms.Both the standard and Taylor patch anastomoses have relatively high wall shear stress gradients in the regions of the toe and heel. For all flow inputs studied nonuniform hemodynamics in the optimized graft design are largely eliminated, and the time-averaged wall shear stress gradients are greatly reduced throughout the anastomotic zone. At resting flow the Taylor patch produces slightly lower wall shear stress gradients in the anastomotic region than the standard end-to-side anastomosis. The optimized design reduces wall shear stress gradients to almost one half of that of the standard and Taylor patch geometries. At exercise flow wall shear stress gradients almost triple in the standard anastomosis and increase approximately 30% in the Taylor patch. In contrast, the geometrically optimized design is basically independent of the type of flow input waveform in terms of time-averaged wall shear stress gradients and disturbed flow patterns.This study demonstrates that it is possible to design a terminal graft geometry for an end-to-side anastomosis that significantly reduces wall shear stress gradients. If the wall shear stress gradient is confirmed to be a major hemodynamic determinant of intimal hyperplasia and restenosis, these results may point to the design of optimal bypass graft geometries.}, number={4}, journal={JOURNAL OF VASCULAR SURGERY}, author={Lei, M and Archie, JP and Kleinstreuer, C}, year={1997}, month={Apr}, pages={637–646} }
 @book{kleinstreuer_1997, title={Engineering fluid dynamics: An interdisciplinary systems approach}, ISBN={0521496705}, DOI={10.1017/cbo9781139174510}, abstractNote={This text provides a thorough treatment of the fundamental principles of fluid mechanics and convection heat transfer and shows how to apply the principles to a wide variety of fluid flow problems. The book is intended for use by final year undergraduate and beginning graduate students in engineering. The focus is on incompressible viscous flows with special applications to non-Newtonian fluid flows, turbulent flows, and free-forced convection flows. A special feature of the text is its coverage of generalised mass, momentum, and heat transfer equations, cartesian tensor manipulations, scale analyses, mathematical modelling techniques and practical solution methods. The final chapter is unique in its case-study approach, applying general modelling principles to analyse non-isothermal flow systems found in a wide range of engineering disciplines. Numerous end-of-chapter sample problem solutions, homework assignments, and mathematical aids are provided to enhance the reader's understanding and problem-solving skills.}, publisher={New York: Cambridge University Press}, author={Kleinstreuer, C.}, year={1997} }
 @article{lei_kleinstreuer_archie_1997, title={Hemodynamic simulations and computer aided designs of graft-artery junctions}, volume={119}, ISSN={["0148-0731"]}, DOI={10.1115/1.2796099}, abstractNote={Severe occlusion of graft–artery junctions due to restenosis, e.g., excessive tissue overgrowth and renewed plaque formation, may occur within a few months or years after bypass surgery. Our hypothesis is that nonuniform hemodynamics, represented by large sustained wall shear stress gradients, trigger abnormal biological processes leading to rapid restenosis and hence early graft failure. In turn, this problem may be significantly mitigated by designing graft-artery bypass configurations for which the wall shear stress gradient (WSSG) is approximately zero and hence nearly uniform hemodynamics are achieved. Focusing on the distal end of several femoral artery bypass junctions, a validated finite volume code has been used to compute the transient three-dimensional velocity vector fields and its first and second surface derivatives in order to test the idea. Specifically, it is shown that the Taylor patch, which generates higher patency rates than standard end-to-side anastomoses, exhibits lower WSSG levels than standard configurations, and that further geometric design improvements reduce the WSSG in magnitude and local extent even more.}, number={3}, journal={JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME}, author={Lei, M and Kleinstreuer, C and Archie, JP}, year={1997}, month={Aug}, pages={343–348} }
 @article{kleinstreuer_li, title={Analysis and computer program for rupture-risk prediction of abdominal aortic aneurysms}, volume={5}, journal={Biomedical Engineering Online}, author={Kleinstreuer, C. and Li, Z. H.} }
 @book{kleinstreuer, title={Biofluid dynamics}, ISBN={0849322219}, publisher={Boca Raton, FL: CRC/Taylor & Francis}, author={Kleinstreuer, C.} }
 @inbook{kleinstreuer_li_feng, title={Computational analysis of enhanced cooling performance and pressure drop for nanofluid flow
in microchannels}, ISBN={9781439861929}, booktitle={Advanced in numerical heat transfer}, publisher={Boca Raton: CRC Press/Taylor & Francis Group}, author={Kleinstreuer, C. and Li, J. and Feng, Y.}, editor={W.J. Minkowycz, E. M. and Sparrow and Abraham, J. P.Editors}, pages={250–273} }
 @article{kleinstreuer, title={Computational nanofluid flow and heat transfer in microchannels}, journal={Handbook of Fluid Dynamics, 2nd Edition}, author={Kleinstreuer, C.} }
 @article{kleinstreuer, title={Entropy generation analysis for nanofluid flow in microchannels}, volume={132}, number={12}, journal={Journal of Heat Transfer}, author={Kleinstreuer, C.} }
 @article{kleinstreuer, title={Microsystems and microfluidics}, journal={Handbook of Fluid Dynamics, 2nd Edition}, author={Kleinstreuer, C.} }