In the stomach, the biological hydrogel known as mucus protects the stomach wall from the damaging effects of strongly acidic digestive juices inside the stomach lumen. Altered mucus function is linked to gastric diseases including ulcers and cancers. The biophysical mechanisms underlying the barrier are not well understood, due partly to a lack of suitable in vitro tools.

In this work, we developed an in vitro microfluidic system designed to mimic mucus secretion in the stomach (see Figure 1) ^[1] . In our system, mucus components are pumped continuously on-chip into an acidic flow, mimicking in vivo mucus secretion into an acidic stomach lumen. A fluorescent pH indicator added to the samples allows optical tracking of acid diffusion. Our microfluidic system is superior to in vitro macroscale techniques currently used to assay mucus function ^[2] . Advantages of our system include study of barrier function under secretion rather than static conditions, ability to optically measure the pH profile inside the mucus layer, and low sample volume requirement enabling experiments using difficult-to-purify mucus components.

With this system, we demonstrate that continuous secretion of mucin glycoprotein, the dominant protein component of mucus, hinders the diffusion of acid (Figure 2) due to the ability of mucins to directly bind and sequester H⁺ (see ^[1] for more details). We further estimate that the barrier function resulting from direct binding of H⁺ to mucin constitutes a significant portion of the in vivo mucus barrier. This “mucus-secretion-on-a-chip” platform may be used to systematically study the barrier function of each mucus layer component, perform diagnostics of mucus function using small amounts of clinical sample, and test mucus-targeted drugs.

1. D. L. Li, O. Lieleg, S. Jang, K. Ribbeck, and J. Han, “Microfludic in vitro system for quantitative study of stomach mucus barrier function,” Lab on a Chip, 2012, to be published. DOI: 10.1039/C2LC40161D.
2. S. Tanaka, H. H. J. Meiselman, E. Engel, P. H. Guth, O. Furukawa, R. B. Wenby, J. Lee, J. D. Kaunitz, “Regional differences of H+, HCO3-, and CO2 diffusion through native porcine gastroduodenal mucus,” Dig. Dis. Sci., vol. 47, no. 5, pp. 967-973, May 2002.