טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentFishler Ramy
SubjectMicrofluidic Models for Studying Pulmonary Acinar Transport
Phenomena
DepartmentDepartment of Biomedical Engineering
Supervisor Professor Josue Sznitman
Full Thesis textFull thesis text - English Version


Abstract

_____________________________________________________________________      Particle transport phenomena in the deep alveolated airways of the lungs (i.e. pulmonary acinus) govern deposition outcomes following inhalation of hazardous or pharmaceutical aerosols. Yet, there is still a dearth of experimental tools for resolving air-flow patterns, particle dynamics and particle deposition inside the acinus. Here, we develop a microfluidic platform that enables quantitative characterization inside acinar-like structures directly at the alveolar scale. In a first step, we investigate quantitatively low-Reynolds-number (Re=0.1, 1 and 10) cavity flow phenomena using a microfluidic screening platform featuring rectangular channels lined with cylindrical cavities. Using particle image velocimetry (PIV) with a glycerol solution as the carrying fluid, supported by computational fluid dynamics (CFD) simulations, we map flow patterns (including attached, recirculating and multi-vortex flow configurations) as a function of geometric parameters. Our results enable better design of acinar models through the selection of cavity geometries that yield a single vortex as expected for in-vivo alveolar flows.

            We next use the screening platform to investigate flow topologies during increasing phases of embryonic life. We analyze flow inside cavities that are representative of three distinct phases of in utero gestation, revealing distinct respiratory alveolar flow patterns throughout different stages of fetal life. While attached, streamlined flows characterize the shallow structures of premature alveoli indicative of the onset of the saccular stage, separated recirculating vortex flows become the signature of developed and extruded alveoli characteristic of the advanced stages of fetal development. Our results provide quantitative experimental and numerical data on flow patterns and wall shear stresses in the developing lung that may have important physiological implications.

            Acinar flow phenomena are next analysed using PIV in a five-generation acinar tree model that expands and contracts periodically. Our data reveal experimentally for the first time a gradual transition of alveolar flow patterns along the acinar tree from recirculating to radial streamlines, in support of hypothesized predictions from past CFD simulations.

            The acinar tree model is next used to study the influence of respiratory flow asynchrony on inhaled aerosol transport by investigating alveolar flow patterns for increasing phase lags between wall motion and acinar ductal flows. The results confirm that alveolar flow patterns are time-dependent in contrast to quasi-steady phenomena that pertain under synchronous conditions. These time dependent flows may increase particle dispersion deep in the lung.

            Finally, we investigate airborne particle dynamics and deposition inside the acinar tree model. We study experimentally captured trajectories of inhaled polydispersed smoke particles (0.2 to 1 µm in diameter), demonstrating how intrinsic particle motion, i.e. gravity and diffusion, is crucial in determining dispersion and deposition of aerosols through a streamline crossing mechanism, a phenomenon specifically important during flow reversal and within alveolar cavities. In addition, we examine the effect of particle size on detailed deposition patterns of monodispersed microspheres between 0.1-2 µm. Our experiments underline local modifications in the deposition patterns due to gravity for particles ≥0.5 µm compared to smaller particles.