Limitations with cell cultures and experimental animal-based studies have had the scientific and industrial communities searching for new approaches that can provide reliable human models for applications such as drug development, toxicological assessment, and in vitro pre-clinical evaluation. This has resulted in the development of microfluidic-based cultures that may better represent organs and organ systems in vivo than conventional monolayer cell cultures. Although there is considerable interest from industry and regulatory bodies in this technology, several challenges need to be addressed for it to reach its full potential. Among those is a lack of guidelines and standards. Therefore, a multidisciplinary team of stakeholders was formed, with members from the US Food and Drug Administration (FDA), the National Institute of Standards and Technology (NIST), European Union, academia, and industry, to provide a framework for future development of guidelines/standards governing engineering concepts of organ-on-a-chip models. The result of this work is presented here for interested parties, stakeholders, and other standards development organizations (SDOs) to foster further discussion and enhance the impact and benefits of these efforts.

Identification and approval of new drugs for use in patients requires extensive preclinical studies and clinical trials. Preclinical studies rely on in vitro experiments and animal models of human diseases. The transferability of drug toxicity and efficacy estimates to humans from animal models is being called into question. Subsequent clinical studies often reveal lower than expected efficacy and higher drug toxicity in humans than that seen in animal models. Microphysiological systems (MPS), sometimes called organ or human-on-chip models, present a potential alternative to animal-based models used for drug toxicity screening. This review discusses multi-organ MPS that can be used to model diseases and test the efficacy and safety of drug candidates. The translation of an in vivo environment to an in vitro system requires physiologically relevant organ scaling, vascular dimensions, and appropriate flow rates. Even small changes in those parameters can alter the outcome of experiments conducted with MPS. With many MPS devices being developed, we have outlined some established standards for designing MPS devices and described techniques to validate the devices. A physiologically realistic mimic of the human body can help determine the dose response and toxicity effects of a new drug candidate with higher predictive power.

We have developed a pumpless cell culture chip that can recirculate small amounts of cell culture medium (400 μL) in a unidirectional or bidirectional flow pattern, producing physiologic levels of shear suitable for culturing endothelial cells.

Microphysiological systems (MPS) that are operated with human tissues often only represent 1/100,000th to 1/50,000th of the human body, where the corresponding amounts of blood surrogate are 60 to 300 µL of cell culture medium. Operating microfluidic cell culture devices that house multiple tissues with such small amounts of recirculating liquid is technically challenging. Here, we have developed a microphysiological cell culture platform that supports the culture of four human tissues (kidney, GI tract, liver, and bone marrow) with 80 µL of cell culture medium. We used the platform to co-culture the tissues for up to 72 h. Cell viability data and the production of urea and albumin over the three days of co-culture indicate that the device we developed is a viable format for short-term operation of MPS with near-physiological amounts of blood surrogate. The system was also capable of reproducing acute liver toxicity to HepG2/C3A liver cells via acetaminophen and troglitazone.