Fig. 2

The two main microfabrication techniques used to generate organs-on-chip. a Photolithography is the core microfabrication technique used to transfer micro- and nanoscale patterns to photosensitive materials by optical radiation. A silicon wafer is used as support for the photo-sensitive material, which is generally called photoresist. After its application on the wafer’s surface, the wafer is spin-coated to obtain a thin uniform film of the photoresist, which is then brought in contact with a photomask that reproduces the desired pattern. The photoresist crosslink in the parts exposed to high-intensity ultraviolet (UV) light; while the covered photoresist is removed by a chemical agent. The negative design of the mask is now reproduced on the silicon master. b Soft lithography allows the fabrication of elastomeric molds using a replica molding technique. The PDMS is cast against the bas-relief pattern of the silicon master photoresist. After a thermal phase, the resulting substrate is peeled off showing the 3D pattern of the original master. The microfluidic device is then generated by creating the needed features, e.g., the inlets, and by bonding it to a PDMS or glass slab. c 3D bioprinting constructs microfluidic devices using a fast and automated process. In the bioprinting nozzle-based approach, the bioink is extruded through a nozzle moved by a computer-controlled arm to create 3D shapes. Superior resolutions are obtained using optical-based approaches where laser exposure solidifies the bioink through a crosslinking reaction