Clamping strategies for organ-on-a-chip devices

Clamping devices have been implemented in organ-on-a-chip systems to facilitate on-chip culture of complex biological models, the performance of various readouts and the selection of proper materials. In this Review, we highlight the current status of clamping technology, its benefits and future devices that promise a major impact in the organ-on-a-chip field. 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.