Bubbling and foaming assisted clearing of mucin plugs in microfluidic Y-junctions Daner Abdula Department of Chemistry, Portland State University, Portland, OR 97201, United States article info Article history: Accepted 24 April 2016 Keywords: Lung Mucus Bifurcation Surfactant Foam abstract Microfluidic Y-junctions were used to study mechanical mechanisms involved in pig gastric mucin (PGM) plug removal from within one of two bifurcation branches with 2-phase air and liquid flow. Water control experiments showed moderate plug removal due to shear from vortex formation in the blockage branch and suggest a PGM yield stress of 35 Pa, as determined by computational fluid dynamics. Addition of hexadecyltrimethylammonium bromide (CTAB) surfactant improved clearing effectiveness due to bubbling in 1 mm diameter channels and foaming in 500 μm diameter channels. Plug removal mechanisms have been identified as vortex shear, bubble scouring, and then foam scouring as air flow rate is increased with constant liquid flow. The onset of bubbling and foaming is attributed to a flow regime transition from slug to slug-annular. Flow rates explored for 1 mm channels are typically experienced by bronchioles in generations 8 and 9 of lungs. Results have implications on treatment of cystic fibrosis and other lung diseases. & 2016 Elsevier Ltd. All rights reserved. 1. Introduction Cystic fibrosis (CF) is a disease caused by improperly operating cystic fibrosis transmembrane conductance regulator (CFTR) which reduces human life expectancy to  38 years (Garcia et al., 2015). The problem is genetic in nature stemming from CFTR mutations which prevent proper regulation of Cl  ions, and hence water, across apical membranes thereby thickening the mucus lining of inner lung passages (Zabner et al., 1998). As mucus builds up, it restricts and eventually blocks respiratory passages to alveoli preventing full oxygenation capacity of hemoglobin in blood, leading to many health complications. Compromising the protec- tive mucosal layer also leaves sensitive lung tissue exposed to inhaled bacteria since the lining cannot act as a trap, eventually resulting in colonization and infection (Costerton et al., 1999). For the most severe cases, highly intrusive surgery or endoscopic mucus removal are options. A myriad of chest physical therapies are also helpful, such as mechanical percussors, "flutter" devices, positive expiratory pressure masks and inflatable therapy vests (Thomas et al., 1995; Warwick and Hansen, 1991), all of which can become uncomfortable for patients due to frequency of use and stress on the body. Medical treatments, which are more easily administered, include antibiotics, bronchodilators which relax bronchioles for dilation and mucinases/proteases/expectorants which act to break down or thin mucus (Flume et al., 2007; Ramsey, 1996). One option of the latter is hypertonic saline administered through a nebulizer which is good for forced vital capacity (FVC) and forced expiratory volume (FEV) improvements of 82 ml and 68 ml respectively (Elkins et al., 2006). Though this study is in vivo, it does not address mechanism of action for the enhancement. Theories include chemical phenomena, such as hydration of the airway surface (Tarran et al., 2001) and mod- ification of lung secretions (King et al., 1997; Wills et al., 1997), but also physical explanations such as provoking coughing (Robinson et al., 1997, 1996) which is known to remove mucus via shear forces (Zahm et al., 1991). Optimal effectiveness would likely include a combination of both mechanical and chemical factors. Two other treatment methods are surfactant replacement therapy (SRT) (Stevens and Sinkin, 2007) and liquid ventilation (LV) (Leach et al., 1996) which instill liquid plugs directly into the trachea that then propagate down into the lungs when the patient inhales. Unfortunately, success is variable in these methods, such as 50% reduction in mortality for SRT, and it is not understood why. Microfluidics can be used to simplify the problem of under- standing 2-phase fluid flow through lungs. Multiple studies of T- junctions have been carried out (Fu et al., 2011; Garstecki et al., 2006; Hoang, 2013; Link et al., 2004; Wolden, 2012), yet they do not capture true bronchial geometry of Y-junction bifurcations nor are there blockages. Of the experiments that have been done with "Y" geometry (Bǎlan et al., 2012; Baudoin et al., 2013; Song et al., 2010), channels were constructed with lithography which creates square or trapezoidal cross-sections instead of truly representative circular pathways, causing liquid flow in "gutter" regions between Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/jbiomech www.JBiomech.com Journal of Biomechanics http://dx.doi.org/10.1016/j.jbiomech.2016.04.028 0021-9290/& 2016 Elsevier Ltd. All rights reserved. E-mail addresses: daner@pdx.edu, danerabdula@gmail.com Please cite this article as: Abdula, D., Bubbling and foaming assisted clearing of mucin plugs in microfluidic Y-junctions. Journal of Biomechanics (2016), http://dx.doi.org/10.1016/j.jbiomech.2016.04.028i Journal of Biomechanics ∎ (∎∎∎∎) ∎∎∎–∎∎∎