Hideki Fujioka

Acoustically detectable cellular-level lung injury induced by fluid mechanical stresses in microfluidic airway systems

We describe a microfabricated airway system integrated with computerized air–liquid two-phase microfluidics that enables on-chip engineering of human airway epithelia and precise reproduction of physiologic or pathologic liquid plug flows found in the respiratory system. Using this device, we demonstrate cellular-level lung injury under flow conditions that cause symptoms characteristic of a wide range of pulmonary diseases. Specifically, propagation and rupture of liquid plugs that simulate surfactant-deficient reopening of closed airways lead to significant injury of small airway epithelial cells by generating deleterious fluid mechanical stresses. We also show that the explosive pressure waves produced by plug rupture enable detection of the mechanical cellular injury as crackling sounds.

Steady Propagation of a Liquid Plug in a Two-Dimensional Channel

In this study, we investigate the steady propagation of a liquid plug within a two-dimensional channel lined by a uniform, thin liquid film. The Navier-Stokes equations with free-surface boundary conditions are solved using the finite volume numerical scheme. We examine the effect of varying plug propagation speed and plug length in both the Stokes flow limit and for finite Reynolds number (Re). For a fixed plug length, the trailing film thickness increases with plug propagation speed. If the plug length is greater than the channel width, the trailing film thickness agrees with previous theories for semi-infinite bubble propagation. As the plug length decreases below the channel width, the trailing film thickness decreases, and for finite Re there is significant interaction between the leading and trailing menisci and their local flow effects. A recirculation flow forms inside the plug core and is skewed towards the rear meniscus as Re increases. The recirculation velocity between both tips decreases with the plug length. The macroscopic pressure gradient, which is the pressure drop between the leading and trailing gas phases divided by the plug length, is a function of U and U2, where U is the plug propagation speed, when the fluid property and the channel geometry are fixed. The U2 term becomes dominant at small values of the plug length. A capillary wave develops at the front meniscus, with an amplitude that increases with Re, and this causes large local changes in wall shear stresses and pressures.

The steady propagation of a surfactant-laden liquid plug in a two-dimensional channel

In this study, we investigate the steady propagation of a liquid plug in a two-dimensional channel lined by a uniform, thin liquid film. The liquid contains soluble surfactant that can exist both in the bulk fluid and on the air-liquid interface. The Navier-Stokes equations with free-surface boundary conditions and the surfactant transport equations are solved using a finite volume numerical scheme. The adsorption/desorption process of the surfactant is modeled based on pulmonary surfactant properties. As the plug propagates, the front meniscus sweeps preexisting interfacial surfactant from the precursor film, and the surfactant accumulates on the front meniscus interface. As the front meniscus converges on the precursor film from the region where the interfacial surfactant concentration is maximized, the Marangoni stress opposes the flow. In this region, the Marangoni stress results in nearly zero surface velocity, which causes the precursor film thickness near the meniscus to be thicker than the leading...

Three-dimensional visualization and morphometry of small airways from microfocal X-ray computed tomography.

Physiological morphometry is a critical factor in the flow dynamics in small airways. In this study, we visualized and analyzed the three-dimensional structure of the small airways without dehydration and fixation. We developed a two-step method to visualize small airways in detail by staining the lung tissue with a radiopaque solution and then visualizing the tissue with a cone-beam microfocal X-ray computed tomographic (CT) system. To verify the applicability of this staining and CT imaging (SCT) method, we used the method to visualize small airways in excised rat lungs. By using the SCT method to obtain continuous CT images, three-dimensional branching and merging bronchi ranging from 500 to 150 microm (the airway generation=8-16) were successfully reconstructed. The morphometry of the small airways (diameter, length, branching angle and gravity angle between the gravity direction and airway vector) was analyzed using the three-dimensional thinning algorithm. The diameter and length exponentially decreased with the airway generation. The asymmetry of the bifurcation decreased with generation and one branching angle decided the other pair branching angle. The SCT method is the first reported method that yields faithful high-resolution images of soft tissue geometry without fixation and the three-dimensional morphometry of small airways is useful for studying the biomechanical dynamics in small airways.

Liquid and surfactant delivery into pulmonary airways

We describe the mechanisms by which liquids and surfactants can be delivered into the pulmonary airways. These are instilled and transported throughout the lung in clinical therapies such as surfactant replacement therapy, partial liquid ventilation and drug delivery. The success of these treatments is contingent on the liquid distribution and the delivery to targeted regions of the lung. The targeting of a liquid plug can be influenced by a variety of factors such as the physical properties of the liquid, the interfacial activity, the gravitational orientation, instillation method and propagation speed. We provide a review of experimental and theoretical studies that examine these effects in single tubes or channels, in tubes with single bifurcations and in the whole lung.

Unsteady propagation of a liquid plug in a liquid-lined straight tube

This paper considers the propagation of a liquid plug driven by a constant pressure within a rigid axisymmetric tube whose inner surface is coated by a thin liquid film. The Navier-Stokes equations are solved using the finite-volume method and the SIMPLEST algorithm. The effects of precursor film thickness, initial plug length, pressure drop across the plug, and constant surface tension on the plug behavior and tube wall mechanical stresses are investigated. As a plug propagates through a liquid-lined tube, the plug gains liquid from the leading front film, and it deposits liquid into the trailing film. If the trailing film is thicker (thinner) than the precursor film, the plug volume decreases (increases) as it propagates. For a decreasing volume, eventually the plug ruptures. Under a specific set of conditions, the trailing film thickness equals the precursor film thickness, which leads to steady state results. The plug speed decreases as the precursor film thins because the resistance to the moving front meniscus increases. As the pressure drop across the plug decreases, the plug speed decreases resulting in thinning of the trailing film. As the plug length becomes longer, the viscous resistance in the plug core region increases, which slows the plug and causes the trailing film to become even thinner. The magnitude of the pressure and shear stress at the tube inner wall is maximum in the front meniscus region, and it increases with a thinner precursor film. As the surface tension increases, the plug propagation speed decreases, the strength of the wall pressure in the front meniscus region increases, and the pressure gradient around the peak pressure becomes steeper.

Liquid plug propagation in flexible microchannels: A small airway model

In the present study, we investigate the effect of wall flexibility on the plug propagation and the resulting wall stresses in small airway models with experimental measurements and numerical simulations. Experimentally, a flexible microchannel was fabricated to mimic the flexible small airways using soft lithography. Liquid plugs were generated and propagated through the microchannels. The local wall deformation is observed instantaneously during plug propagation with the maximum increasing with plug speed. The pressure drop across the plug is measured and observed to increase with plug speed, and is slightly smaller in a flexible channel compared to that in a rigid channel. A computational model is then presented to model the steady plug propagation through a flexible channel corresponding to the middle plane in the experimental device. The results show qualitative agreements with experiments on wall shapes and pressure drops and the discrepancies bring up interesting questions on current field of modeling. The flexible wall deforms inward near the plug core region, the deformation and pressure drop across the plug increase with the plug speed. The wall deformation and resulting stresses vary with different longitudinal tensions, i.e., for large wall longitudinal tension, the wall deforms slightly, which causes decreased fluid stress and stress gradients on the flexible wall comparing to that on rigid walls; however, the wall stress gradients are found to be much larger on highly deformable walls with small longitudinal tensions. Therefore, in diseases such as emphysema, with more deformable airways, there is a high possibility of induced injuries on lining cells along the airways because of larger wall stresses and stress gradients.

Effects of gravity, inertia, and surfactant on steady plug propagation in a two-dimensional channel

Liquid plugs may form in pulmonary airways during the process of liquid instillation or removal in many clinical treatments. Studies have shown that the effectiveness of these treatments may depend on how liquids distribute in the lung. Better understanding of the fundamental fluid mechanics of liquid plug transport will facilitate treatment strategies. In this paper, we develop a numerical model of steady plug propagation driven by gravity and pressure in a two-dimensional liquid-lined channel oriented at an angle α with respect to gravity. We investigate the effects of gravity through the Bond number, Bo, and α; the plug propagation speed through the capillary number, Ca, or the Reynolds number, Re; the plug length LP, and the surfactant concentration C0. Without gravity, i.e., Bo=0, the plug is symmetric, and there are two regimes for the flow: two wall layers and two trapped vortices in the core. There is no flow interaction between the upper and lower half plug domains. When Bo≠0 and α≠0, π, fluid is...

Pulsatile Flow and Mass Transport Over an Array of Cylinders: Gas Transfer in a Cardiac-Driven Artificial Lung

The pulsatile flow and gas transport of a Newtonian passive fluid across an array of cylindrical microfibers are numerically investigated. It is related to an implantable, artificial lung where the blood flow is driven by the right heart. The fibers are modeled as either squared or staggered arrays. The pulsatile flow inputs considered in this study are a steady flow with a sinusoidal perturbation and a cardiac flow. The aims of this study are twofold: identifying favorable array geometry/spacing and system conditions that enhance gas transport; and providing pressure drop data that indicate the degree of flow resistance or the demand on the right heart in driving the flow through the fiber bundle. The results show that pulsatile flow improves the gas transfer to the fluid compared to steady flow. The degree of enhancement is found to be significant when the oscillation frequency is large, when the void fraction of the fiber bundle is decreased, and when the Reynolds number is increased; the use of a cardiac flow input can also improve gas transfer. In terms of array geometry, the staggered array gives both a better gas transfer per fiber (for relatively large void fraction) and a smaller pressure drop (for all cases). For most cases shown, an increase in gas transfer is accompanied by a higher pressure drop required to power the flow through the device.

Effects of inertia and gravity on liquid plug splitting at a bifurcation

Liquid plugs may form in pulmonary airways during the process of liquid instillation or removal in many clinical treatments. During inspiration the plug may split at airway bifurcations and lead to a nonuniform final liquid distribution, which can adversely affect treatment outcomes. In this paper, a combination of bench top experimental and theoretical studies is presented to study the effects of inertia and gravity on plug splitting in an airway bifurcation model to simulate the liquid distributions in large airways. The splitting ratio, Rs, is defined as the ratio of the plug volume entering the upper (gravitationally opposed) daughter tube to the lower (gravitationally favored) one. Rs is measured as a function of parent tube Reynolds number, Rep; gravitational orientations for roll angle, phi, and pitch angle, gamma; parent plug length LP; and the presence of pre-existing plug blockages in downstream daughter tubes. Results show that increasing Rep causes more homogeneous splitting. A critical Reynolds number Rec is found to exist so that when Rep < or = Rec, Rs = 0, i.e., no liquid enters the upper daughter tube. Rec increases while Rs decreases with increasing the gravitational effect, i.e., increasing phi and gamma. When a blockage exists in the lower daughter, Rec is only found at phi = 60 deg in the range of Rep studied, and the resulting total mass ratio can be as high as 6, which also asymptotes to a finite value for different phi as Rep increases. Inertia is further demonstrated to cause more homogeneous plug splitting from a comparison study of Rs versus Cap (another characteristic speed) for three liquids: water, glycerin, and LB-400X. A theoretical model based on entrance flow for the plug in the daughters is developed and predicts Rs versus Rep. The frictional pressure drop, as a part of the total pressure drop, is estimated by two fitting parameters and shows a linear relationship with Rep. The theory provides a good prediction on liquid plug splitting and well simulates the liquid distributions in the large airways of human lungs.