Organ-like surrogates can be created using microfluidic devices to recreate air-liquid interfaces, cell-cell communication and complex tissue mechanics. Such “organ-on-a-chip” devices are powerful tools to study a functional alveolar-capillary interface, relevant to infection, inflammation, and lung dysfunction and acute lung injury.
The upper and lower layers of the microfluidic device shown in the figures were produced by casting PDMS prepolymer against a photolithographically prepared master that contains a positive relief of parallel microchannels made of photoresist (SU8- 50, MicroChem). The weight ratio of PDMS base to curing agent was 15:1. The crosssectional size of the microchannels is 400 μm (width) X 70 μm (height) for the central culture channels and 200 μm (width) X 70 μm (height) for the side channels. Thin microporous PDMS membranes were generated by spin-coating PDMS prepolymer (15:1) on a silanized wafer that has an array of 50 μm-tall pentagonal posts fabricated by using standard photolithographic techniques. Spin-coating at 2500 rpm for 10 minutes produced 10 μm-thick PDMS membranes with pentagonal throughholes. After curing at 65ºC overnight the membrane surface was briefly treated with corona plasma generated by a hand-held corona treater (Electro-Technic Products) and brought in conformal contact with the upper PDMS substrate to achieve irreversible bonding between the layers. After overnight incubation at 65ºC, the bottom surface of the membrane was treated with corona and permanently bonded to the lower PDMS layer after careful manual. Following cell culture, the device allows immunostaining of junctional complexes, permeability assay, trans-bilayer electrical resistance measurements, ROS detection, immunostaining, inflammatory cell adhesion, and bacterial infection.