Numerical models for organ-on-a-chip: A systematic review and analyses.

Organs-on-a-chip (OoCs) are considered key tools for life science, medicine, and pharmaceutical research and can provide great insights into pathophysiologies of human organs. However, experimental studies of OoCs are commonly limited by their reliable geometrical design, realistic experimental parameter settings, biosensor measurement positions, and the rarity of cells available for particular diseases. In this paper, a review of 124 research articles published between 2000 and 2024 on OoCs and various numerical models applicable to them have been carried out. This article systematically reviews the development and application of mathematical models for the simulation of various OoCs for organs such as the gut, liver, and heart. The review also covered the evaluation of the accuracies of the momentum transport, mass transfer, and energy transfer in the mathematical models applicable to various OoCs. Analysis of the theoretical and experimental results from the reviewed articles on optimization of the OoC structure and parameter settings have also been carried out. From the review, numerical simulations were found to show great potential for optimizing the OoC structure, help minimize experimental times, provide good prediction of the experimental results, as well as offer insights into the interaction between different OoC types. Overall, this review establishes a theoretical foundation for the future organ-on-a-chip design, beneficial for biological experiments, as well as drug performance analysis.