Figure 1. Microengineering technologies used to construct 3D culture systems and organs-on-chips.

(a) Photolithography is a core microfabrication technique used to transfer microscale patterns to photosensitive materials by selective exposure to optical radiation. A silicon wafer is spin coated with a thin uniform film of a photosensitive material (photoresist), which is then aligned and brought in close contact with a photomask that typically consists of a transparent glass plate covered with a pattern defined by opaque chrome layers; the microscale pattern desired by the user is generated with computer-assisted design software. This is followed by exposure of the photoresist to high-intensity ultraviolet (UV) light through the photomask, which protects some regions of the photoresist from UV and exposes others based on the design of the pattern. UV-exposed areas become soluble in a developer solution and dissolve away during the following step, called development, thus leaving the desired microscale pattern etched into the photoresist. (b) Soft lithography involves fabrication of elastomeric stamps using a replica-molding technique in which liquid prepolymer of PDMS is cast against the bas-relief pattern of photoresist produced by photolithography (a) to generate a PDMS substrate that replicates the 3D topography of the original master. In microcontact printing, the PDMS stamp is inked with protein solution, dried, and brought in conformal contact with a surface for a period ranging from 30s to several minutes. Upon removal of the stamp, a pattern is generated on the surface that is defined by the raised bas-relief structure of the stamp, and hence precisely recreates the microscale pattern of the original master. (c) Microfluidic devices are typically created by bonding a PDMS substrate containing microchannel features created by replica molding with a blank PDMS slab. In these microdevices, two fluids (red and green) flowing through independent inlets meet at a Y-junction and enter a straight microchannel in which they flow in adjacent, laminar streams without mixing (arrows indicate flow direction; scale bar, 500 µm). Reproduced from [84] with permission.