Roadblocks confronting widespread dissemination and deployment of Organs on Chips

Abstract

Organ on Chip platforms hold significant promise as alternatives to animal models or traditional cell cultures, both of which poorly recapitulate human pathophysiology and human level responses. Within the last 15 years, we have witnessed seminal scientific developments from academic laboratories, a flurry of startups and investments, and a genuine interest from pharmaceutical industry as well as regulatory authorities to translate these platforms. This Perspective identifies several fundamental design and process features that may act as roadblocks that prevent widespread dissemination and deployment of these systems, and provides a roadmap to help position this technology in mainstream drug discovery.

Fig. 1. Gartner hype cycle for Organs on Chips.

The Gartner hype cycle for Organs on Chips demonstrates how key events in the development of Organs on Chips can stimulate expectations of Organs on Chips within the scientific and general community. It also warns of the potential disillusionment that can occur if Organ on Chip dissemination is limited by a lack of stakeholder engagement.

Fig. 2. Stakeholder engagement in the iterative development process of Organs on Chips.

A visual representation of the cyclic and iterative process that is critical to the development and usage of Organs on Chips. Within each segment, the general roles of individual stakeholders are highlighted in their individual iterative process as well as their role moving towards widespread dissemination of Organs on Chips.

Fig. 3. PDMS and plastic based manufacturing methods for Organs on Chips.

A Photolithography based Organ on Chip fabrication begins with the formation of a mold with raised features via standard photolithography methods. PDMS can then be cast onto the mold to form a PDMS chip with negative spaces that form the microfluidic channels of the final PDMS-based Organ on Chip. B Micromilled Organs on Chip devices are milled via subtractive manufacturing techniques. Micromachining tools remove excess material from a plastic substrate resulting in the formation of the channels and features of an individual Organ on Chip. C 3D printed Organs on Chips are formed by the sequential deposition of a thermoplastic in thin layers to form the shape and features of an Organ on Chip. D Injection molded Organs on Chips start by the creation of a reusable external mold with positive features that correspond to negative spaces in the Organ on Chip design. The mold can then be filled with a liquid thermoplastic. Once the thermoplastic has set, the molded Organ on Chip can be removed from the mold.