Organ-on-chip applications in drug discovery: an end user perspective

Abstract

Organ-on-chip (OoC) systems are in vitro microfluidic models that mimic the microstructures, functions and physiochemical environments of whole living organs more accurately than two-dimensional models. While still in their infancy, OoCs are expected to bring ground-breaking benefits to a myriad of applications, enabling more human-relevant candidate drug efficacy and toxicity studies, and providing greater insights into mechanisms of human disease. Here, we explore a selection of applications of OoC systems. The future directions and scope of implementing OoCs across the drug discovery process are also discussed.

Keywords: drug development; drug discovery; microfluidic models; organ-on-a-chip.

Figure 1.. Schematic diagram depicting an example of a basic liver-on-chip model as a representative organ-on-chip (OoC).

The active flow within the channel of a chip enables cells to be perfused with media containing oxygen and nutrients (inlet) and the removal of waste products and the sampling of metabolites for assessment of cell function (outlet). This schematic is for illustrative purposes only and does not represent any particular existing OoC model or all possible types of OoC models. It is intended to exemplify some of the basic bioengineering principles required for the development of an OoC unit.

Figure 2.. Examples of commercialised organ-on-chip (OoC) systems.

(A) The HUMINIC chip 4 manufactured by Tissuse. (B) The OrganoPlate® 2-lane 96 manufactured by MIMETAS. (C) The PhysioMimix™ OoC manufactured by CN-Bio. The pictures are reprinted courtesy of the manufacturers and with their permission.

Figure 3.. Timeline for the evolution of organ-on-chip (OoC).

The first OoC model to accomplish organ-level functionality, tissue–tissue interactions and a physiologically relevant organ microenvironment with vascular perfusion came in 2007 as a lung-on-chip by Huh et al. Since then, funding from organisations such as DARPA and NIH, and the founding of Wyss Institute, has propelled OoC technology from a nascent idea to a rapidly growing area of research with potential for utility across the drug discovery process. DARPA, Defence Advanced Research Projects Agency; FDA, US Food and Drug Administration; IO, immuno-oncology; MEM, micro electromechanical system; microTAS; miniaturised total chemical analysis system; NIH, National Institute of Health; PDMS, polydimethylsiloxane; TCTCs, Tissue Chip Testing Centers.