A microfluidic model to study fluid dynamics of mucus plug rupture in small lung airways

Abstract

Fluid dynamics of mucus plug rupture is important to understand mucus clearance in lung airways and potential effects of mucus plug rupture on epithelial cells at lung airway walls. We established a microfluidic model to study mucus plug rupture in a collapsed airway of the 12th generation. Mucus plugs were simulated using Carbopol 940 (C940) gels at concentrations of 0.15%, 0.2%, 0.25%, and 0.3%, which have non-Newtonian properties close to healthy and diseased lung mucus. The airway was modeled with a polydimethylsiloxane microfluidic channel. Plug motion was driven by pressurized air. Global strain rates and shear stress were defined to quantitatively describe plug deformation and rupture. Results show that a plug needs to overcome yield stress before deformation and rupture. The plug takes relatively long time to yield at the high Bingham number. Plug length shortening is the more significant deformation than shearing at gel concentration higher than 0.15%. Although strain rates increase dramatically at rupture, the transient shear stress drops due to the shear-thinning effect of the C940 gels. Dimensionless time-averaged shear stress, T xy , linearly increases from 3.7 to 5.6 times the Bingham number as the Bingham number varies from 0.018 to 0.1. The dimensionless time-averaged shear rate simply equals to T xy /2. In dimension, shear stress magnitude is about one order lower than the pressure drop, and one order higher than yield stress. Mucus with high yield stress leads to high shear stress, and therefore would be more likely to cause epithelial cell damage. Crackling sounds produced with plug rupture might be more detectable for gels with higher concentration. V C 2015 AIP Publishing LLC. [http://dx

Effects of Surface Tension and Yield Stress on Mucus Plug Rupture: A Numerical Study

“…Comparing our results with literature studies (e.g. our previous research by Hu et al (2015)) shows that the dimensions of the channel and of the plug have played an important role on rupture dynamics, which parameters, however, have not been investigated in this study. This study is therefore to be considered as a first insight into the effects of surface tension and yield stress for viscoplastic flows, and further simulations would help strengthen the conclusions drawn in BIO-19-1361.…”

“…In a previous study, we experimentally investigated the mucus plug rupture in a collapsed lung airway of the 10 th generation by using a microfluidic model with carbopol gels as mucus simulant (Hu 2015). Our experiments showed near rupture appear rapid changes in shear stress and plug-shortening velocity.…”

“…Figure 1(a) depicts the sketch of our model which consists of a mucus plug in a channel. The channel is 1.5 mm (2a) wide, 0.12 mm (h) deep and 10 mm (l) long, similar to that used in our experiments (Hu 2015), except for the length (50 mm in the experiments). In the following, the two walls normal to the yaxis are called the y-walls, or front (y=0) and back (y=2a) walls, whereas the two walls normal to the zaxis are termed the z-walls, or bottom (z=0) and top (z=h) walls.…”

Biomimetics of the pulmonary environment in vitro: A microfluidics perspective

“…Although these studies have significantly advanced our understanding of plug dynamics, efforts have been mainly limited to Newtonian solutions evocative of surfactant-laden aliquot delivery (i.e., surfactant replacement therapy) to the alveolar regions. There are to date few microfluidic attempts that have concentrated on mucus plug transport 87 . Indeed, the non-Newtonian, viscoelastic properties of the mucus gel layer 88 leave open questions on the dynamics of mucus transport and its interactions with the underlying bronchial epithelium, in particular, when subject to rheological changes under bronchial infections or disease 89 (e.g., cystic fibrosis).…”

Organoids, organs-on-chips and other systems, and microbiota

“…The benefit of developing such systems is that it provides a platform to study the complex physiological and pathophysiological responses of tissues at an organ level, to provide patients with quicker access to new medication. For example, microfluidics can be utilised to mimic blood and nutrient flow and maintain mucus transition in lung epithelia [108,109]. In addition, this system can be exploited to complement animal studies and also more accurately predict pharmacological effects in patients and, in the future, could be used to bypass the use of animal testing completely [110].…”