Clamping strategies for organ-on-a-chip devices

Organ-on-a-chip devices have enabled major breakthroughs in biomedical research, but they have yet to be successfully translated to the pharmaceutical industry. Traditional microfluidic devices rely on irreversible bonding techniques to seal fluidic channels, which limit their accessibility and automation and can be labour-intensive to operate. New and more versatile chip designs are urgently needed to enable industrial applications and to support complex, 3D cell cultures. Clamps allow microdevices to be opened and closed before, after and during operation, such that cells can be directly accessed whenever needed. This versatility facilitates the incorporation of more physiologically relevant 3D in vitro models, including organoids, and allows a wider range of on-chip and off-chip biochemical assays. This Review describes the current trend from irreversible chip bonding to innovative, reversible fastening techniques. We introduce the concept of Lock-and-Play devices as emerging tools that can provide a leak-tight seal in a single step for high-throughput applications. Finally, we analyse the applications in which Lock-and-Play devices are likely to have the biggest impact for the drug development industry.