Organ-on-Chips for Studying Tissue Barriers: Standard Techniques and a Novel Method for Including Porous Membranes Within Microfluidic Devices.

A relevant number of organ-on-chips is aimed at modeling epithelial/endothelial interfaces between tissue compartments. These barriers help tissue function either by protecting (e.g., endothelial blood-brain barrier) or by orchestrating relevant molecular exchanges (e.g., lung alveolar interface) in human organs. Models of these biological systems are aimed at characterizing the transport of molecules, drugs or drug carriers through these specific barriers. Multilayer microdevices are particularly appealing to this goal and techniques for embedding porous membranes within organ-on-chips are therefore at the basis of the development and use of such systems. Here, we discuss and provide procedures for embedding porous membranes within multilayer organ-on-chips. We present standard techniques involving both custom-made polydimethylsiloxane (PDMS) membranes and commercially available plastic membranes. In addition, we present a novel method for fabricating and bonding PDMS porous membranes by using a cost-effective epoxy resin in place of microfabricated silicon wafers as master molds.