Clement Kleinstreuer

• North Carolina State University

Understanding the profound complexity of particle-laden flows is critical to advances across multiple disciplines. This review aims to provide a comprehensive framework for understanding these multiphase systems, addressing both their fundamental physics and diverse modeling approaches. By beginning with effective single-phase models that are chara...

Non-uniform hemodynamic factors are believed to play important roles in the onset and development of atherosclerotic lesions in branching blood vessels and intimal hyperplasia at graft-artery bypass junctions. At present, a variety of theories regarding the hemodynamic aspects of atherogenesis have been proposed, which include almost all hemodynami...

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 GlaxoSmi...

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 ne...

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...

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...

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...

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, in...

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 transpor...

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....

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 th...

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 inform...

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...

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 laborat...

Multifunctional nanoparticles have the potential for an expanded use in visualization, diagnostics and treatment of a variety of diseases. This mini-review discusses biological and synthetic nanoparticles and their applications to combat cardiovascular ailments. Specifically, different types of nanodrug targeting methods are outlined, numerous case...

Link: https://www.tandfonline.com/doi/abs/10.1080/02786826.2018.1476751 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...

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 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 inabili...

This chapter presents the fundamentals of computational microfluidics with applications in pulmonary and arterial drug delivery. It also presents the modeling methods of micro-biofluid dynamics. The chapter focuses on the general conservation laws that govern the transport of fluids, and the modeling approaches for specific aims such as two-phase f...

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 phys...

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 f...

Acute lung injury and acute respiratory distress syndrome (ARDS) represent a heterogenous group of lung disease in critically ill patients that continues to have high mortality. Despite the increased understanding of the molecular pathogenesis of ARDS, specific targeted treatments for ARDS have yet to be developed. ARDS represents an unmet medical...

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...

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 lun...

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 simulation...

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...

There is a growing range of applications of nanoparticle-suspension flows with or without heat transfer. Examples include enhanced cooling of microsystems with low volume-fractions of nanoparticles in liquids, improved tribological performance with lubricants seeded with nanoparticles, optimal nanodrug delivery in the pulmonary as well as the vascu...

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 t...

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...

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 down...

Using the open-source software OpenFOAM as the solver, a novel approach to calculate microsphere transport and deposition in a 1-D human lung-equivalent trumpet model is presented. Specifically, for particle deposition in a non-linear trumpet-like configuration a new radial force has been developed which, along with the regular drag force, generate...

Targeted drug delivery to solid tumors is a very active research area, focusing mainly on improved drug formulation and associated best delivery methods/devices. Drug-targeting has the potential to greatly improve drug-delivery efficacy, reduce side effects, and lower the treatment costs. However, the vast majority of drug-targeting studies assume...

High concentration photovoltaic devices require effective heat rejection to keep the solar cells within a suitable temperature range and to achieve acceptable system efficiencies. Various techniques have been developed to achieve these goals. For example, nano fluids as coolants have remarkable heat transfer characteristics with broad applications;...

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 pressu...

Realistic and accurate computer simulations of the particle-hemodynamics in arterial systems can be a valuable tool for numerous biomedical applications. Examples include optimal by-pass grafting and optimal drug-delivery, as well as best medical management concerning the cardio-vascular system. However, such numerical analyses require large comput...

Fluidics originated as the description of pneumatic and hydraulic control systems, where fluids were employed (instead of electric currents) for signal transfer and processing. Microfluidics and Nanofluidics: Theory and Selected Applications offers an accessible, broad-based coverage of the basics through advanced applications of microfluidics and...

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 s...

This chapter outlines several internal laminar fluid flow and fluid-particle transport studies. First, transient laminar flow and steady particle suspension flow in single bifurcations are solved as demonstration projects. Such results could serve as validations of more complex computer simulation programs for which experimental observations are la...

This chapter presents results that provide some interesting insight to the physics of fluid flow. They form base-case solutions to a family of engineering applications, such as film coating, numerous internal flows, simple lubrication as well as non-Newtonian fluid flows, such as exotic oils, blood, paints, and polymeric liquids. In numerous natura...

This chapter begins with an overview, and then discusses the differences between macroscale and nanoscale material structures and thermodynamics. An industrial example of nanofluidics is fluid flow in carbon nanotubes with applications in nanomedicine and material processing. The chapter illustrates through a chart, the information and tools needed...

“Applications in nanofluidics” implies insightful results from analytic or numerical solutions of somewhat idealized fluid flow in nanochannels or fluid-nanoparticle transport phenomena in microchannels. They play essential roles in nanotechnology and contribute to the proper design and operation of microsystems. This chapter introduces metal nanop...

This chapter provides details about microchannel flow theory and microfluidic system components. Microfluidic devices are manufactured using planar substrates such as silicon wafers, glass slides, ceramic blocks, stainless steel, polymer, or even paper chips. System integration implies the combination of independent components and their associated...

This chapter depicts essential system modeling and problem solution steps, with possible feedback if the actual results do not match expectations or measurements. It illustrates, through a chart, the key aspects of mathematical modeling. A mathematical model represents a real process by describing key transport phenomena in terms of partial differe...

Fluid flow and particle transport in microchannels, being part of basic MEMS, laboratory-on-chip (LoC), and point-of-care (PoC) devices, generally deal with aqueous solutions and nano/microsphere suspensions which require micropumps. This chapter illustrates the applications of fluid-particle flow in microchannels and the workings of micropumps. It...

Background Implementation of a patented 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...

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...

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 co...

This is the second article of the two-part paper, combining high-resolution computer simulation results of inhaled nanoparticle deposition in a human airway model (Kolanjiyil and Kleinstreuer [1]) with a new multi-compartmental model for insoluble nanoparticle barrier mass transfer into systemic regions. Specifically, it allows for the prediction o...

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 multi-c...

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 f...

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 Eul...

As part of 'transport in biological media', targeted drug delivery (TDD) is an intense research area encompassing several engineering branches as well as molecular pharmaceutics. It essentially involves connecting a drug release (or injection) point to a predetermined site with the goals of high efficacy and safety via controlled drug release locat...

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 suffici...

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 re...

Contributions to rupture-risk assessment and surgical repair of abdominal aortic aneurysms (AAAs) are reviewed. AAA-rupture occurs when the local wall stress exceeds the subject's vessel-wall strength. Such an event is quite unpredictable and rarely foreshadowed by warning symptoms, but lethal in 80-90% of all cases. Typically, open surgery or endo...

Fine to ultrafine materials, such as spherical particles and fibers with their diverse applications ranging from cosmetics, cleaners and composites to nanomedicine are increasingly ubiquitous in the air we breathe. For example, the unique lung deposition patterns of nanoparticles and their ease-of-migration into the blood stream may cause severe he...

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 airwa...

Building on previous studies in which the transport and targeting of (90)Y microspheres for liver tumor treatment were numerically analyzed based on medical data sets, this two-part paper discusses the influence of an anchored, radially adjustable catheter on local blood flow and microsphere delivery in an idealized hepatic artery system (Part I)....

In this second part, the methodology for optimal tumor-targeting is further explored, employing a patient-inspired hepatic artery system which differs significantly from the idealized configuration discussed in Part I. Furthermore, the fluid dynamics of a microsphere supply apparatus is also analyzed. The best radial catheter positions and particle...

This is a two-part paper, which proposes a new theory explaining the experimentally observed enhancement of the thermal conductivity, k nf, of nanofluids (Part I) and discusses simulation results of nanofluid flow in a radial parallel-plate channel using different k nf-models (Part II). Specifically, Part I provides the derivation of the new model...

This is the second part of a two-part paper which proposes a new theory explaining the experimentally observed enhancement of the thermal conductivity, k nf, of nanofluids (Part I) and discusses simulation results of nanofluid flow in an axisymmetric jet-impingement cooling system using different k nf-models (Part II). Specifically, Part II provide...

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 deposit...

High heat loads of mechanical, chemical, and biomedical microsystems require heat exchangers which are very small, robust, and efficient. Nanofluids are dilute suspensions of nanoparticles in liquids, which may exhibit remarkable heat transfer characteristics, especially for heat removal in micro-devices. Minimization of entropy generation is poten...

Relying on benchmark experimental data sets for flow in conduits with local constrictions, LES and three widely used RANS turbulence models, i.e. the low Reynolds number (LRN) k‐ω model, standard k‐ω model and shear stress transport (SST) transition model, were compared and evaluated to gain new physical insight and provide useful turbulence modeli...

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, assumi...

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 it...

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...

ABSTRACT: Correction to Kleinstreuer C, Feng Y: Experimental and theoretical studies of nanofluid thermal conductivity enhancement: a review. Nanoscale Research Letters 2011, 6:229.

A rising therapy for liver tumor treatment is the local delivery of Yttrium-90 (90Y) radiation via the injection of radioactive microspheres into the hepatic arteries. The elevated arterial blood flow supplying the liver tumor(s) hopefully directs the microspheres towards tumor cells rather than healthy liver tissue. While limited in precise contro...

Nanofluids, i.e., well-dispersed (metallic) nanoparticles at low- volume fractions in liquids, may enhance the mixture's thermal conductivity, knf, over the base-fluid values. Thus, they are potentially useful for advanced cooling of micro-systems. Focusing mainly on dilute suspensions of well-dispersed spherical nanoparticles in water or ethylene...

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 Q(tota...

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 general...

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 implement...

The number of patients afflicted with liver tumors continues to rise being a major concern of international healthcare. Yttrium-90 microsphere radioembolization can be an effective and safe treatment of unresectable primary and secondary liver tumors, and has the potential to be a forefront treatment option for tumor-afflicted patients. Computation...

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 st...

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...

Employing a validated computer simulation model, entropy generation is analyzed in trapezoidal microchannels for steady laminar flow of pure water and CuO-water nanofluids. Focusing on microchannel heat sink applications, local and volumetric entropy rates caused by frictional and thermal effects are computed for different coolants, inlet temperatu...

Fluid mechanics, dissolved species transport and particle dynamics phenomena play major roles in normal and pathological processes occurring in the human body. Most evident on the macro-scale are the transport phenomena associated with blood flow supplying oxygen and nutrients to organs, and airflow in the lung enabling the O2 – CO2 gas exchange. O...

The previous chapter featured several examples to illustrate each topic introduced (or just reviewed) in Sects. 2.2–2.5. They included 5 a few special cases of the conservation laws in both integral form [i.e., the simplified Reynolds Transport Theorem (RTT)] and differential form [i.e., the reduced Navier–Stokes (N–S) equations]. In this chapter,...

“Fluid dynamics” implies fluid flow and associated forces described by vector equations, while convective heat transfer and species mass transfer are described by scalar transport equations. Specifically, this chapter reiterates some basic definitions and continuum mechanics concepts with an emphasis on how to describe standard fluid flow phenomena...

Internal fully-developed flows, such as Couette and Poiseuille, are completely dominated by viscous effects throughout the entire flow domain. In contrast, entrance flows and external flows feature highly viscous effects confined to rapidly growing “boundary layers” in the entrance region, or to thin shear layers along the solid surface. Clearly, t...

Computational fluid dynamics (CFD) methods are well documented (e.g., Versteeg & Malalasekera 1996; Tannehill et al. 1997; Ferziger & Peric 2002; Durbin & Medic 2007; Tu et al. 2008; among others). They are routinely applied to gain new physical insight and to improve engineering system design and hence performance. Nowadays in aircraft, automobile...

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 thei...

IntroductionMicrofluidic DevicesNanodrug DeliveryBio-MEMS ApplicationsConclusions and Future PerspectiveReferences

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...

The trachea is a tubular structure which serves as the conduit which air travels to the lung. It originates just below the vocal cords, courses inferiorly into the thoracic cavity, then bifurcates into two main bronchi, each of which serve one side of lung. Those main bronchi then branch into smaller airways serving individual lobes of each side of...

Knowledge of the geometric characteristics of actual human tracheobronchial (TB) airways is crucial for realistic and accurate computer simulations and experimental studies. An area of particular interest is drug delivery in the respiratory system to combat various diseases, such as COPD/asthma, diabetes and certain cancers. Deposition in the upper...