A Microfluidic Model of Biomimetically Breathing Pulmonary Acinar Airways

Abstract

Quantifying respiratory flow characteristics in the pulmonary acinar depths and how they influence inhaled aerosol transport is critical towards optimizing drug inhalation techniques as well as predicting deposition patterns of potentially toxic airborne particles in the pulmonary alveoli. Here, soft-lithography techniques are used to fabricate complex acinar-like airway structures at the truthful anatomical length-scales that reproduce physiological acinar flow phenomena in an optically accessible system. The microfluidic device features 5 generations of bifurcating alveolated ducts with periodically expanding and contracting walls. Wall actuation is achieved by altering the pressure inside water-filled chambers surrounding the thin PDMS acinar channel walls both from the sides and the top of the device. In contrast to common multilayer microfluidic devices, where the stacking of several PDMS molds is required, a simple method is presented to fabricate the top chamber by embedding the barrel section of a syringe into the PDMS mold. This novel microfluidic setup delivers physiological breathing motions which in turn give rise to characteristic acinar air-flows. In the current study, micro particle image velocimetry (µPIV) with liquid suspended particles was used to quantify such air flows based on hydrodynamic similarity matching. The good agreement between µPIV results and expected acinar flow phenomena suggest that the microfluidic platform may serve in the near future as an attractive in vitro tool to investigate directly airborne representative particle transport and deposition in the acinar regions of the lungs.

Investigation on Microparticle Transport and Deposition Mechanics in Rhythmically Expanding Alveolar Chip

“…Based on the microfluidic technology, human alveoli-on-a-chip was built to study the fluid flow and particle transport and deposition. Sznitman’s group [ 30 , 31 , 32 , 33 ] developed a 5-generation alveolar chip in real size. By controlling the pressure in the surrounding chambers, the periodical expansion and contraction of the channel wall was achieved.…”

Organ-on-a-Chip: Opportunities for Assessing the Toxicity of Particulate Matter

“…In 2016, Benam et al used this technology to test smoking and non-smoking conditions, and confirmed that using the lung-on-a-chip yielded experimental results that were closer to clinical physiological and inflammatory reactions compared with those from animal experiments, and previously undiscovered biomarkers that were even more accurate were found and analyzed (Benam et al, 2016a). At the same time, other teams have developed lung chip models with different design structures and physiological responses (Fishler et al, 2015;Fishler and Sznitman, 2016;Humayun et al, 2018;Stucki et al, 2018;Khalid et al, 2020). The lung-on-a-chip have been developed to demonstrate their importance in drug development and disease models, but still have several practical challenges must be overcome if such devices are to be used in toxicology research and application (Low and Tagle, 2017;Wu et al, 2020).…”

Physiological and Disease Models of Respiratory System Based on Organ-on-a-Chip Technology

“…Unlike traditional microfluidic devices that require stacking multiple PDMS molds, they proposed a simple method for manufacturing the top cavity by embedding the syringe barrel partly into the PDMS mold. This novel design can provide physiological respiratory movement, which generates airflow similar to that under physiological conditions [ 54 , 55 ]. In addition, Katan et al designed a chip to study the flow topology in the fetal lung at the embryonic stage, reproducing the true proportions of the fetal airway in three different pregnancy stages and revealing the unique flow patterns at different stages of fetal life [ 56 ].…”