Numerical evaluation and experimental validation of fluid flow behavior within an organ-on-a-chip model

Abstract

Background and objective: By combining biomaterials, cell culture, and microfluidic technology, organ-on-a-chip (OoC) platforms have the ability to reproduce the physiological microenvironment of human organs. For this reason, these advanced microfluidic devices have been used to resemble various diseases and investigate novel treatments. In addition to the experimental assessment, numerical studies of biodevices have been performed aiming at their improvement and optimization. Despite considerable progress in numerical modeling of biodevices, the validation of these computational models through comparison with experimental assays remains a significant gap in the current literature. This step is critical to ensure the accuracy and reliability of numerical models, and consequently enhance confidence in their predictive results. The aim of the present work is to develop a numerical model capable of reproducing the fluid flow behavior within an OoC, for future investigations, encompassing the geometry optimization.

Methods: In this study, the validation of a numerical model for an OoC microfluidic device was undertaken. This comprised both quantitative and qualitative assessments of trace microparticles flowing through a physical OoC model. High-speed microscopy images of the flow, using a blood analog fluid, were analyzed and compared with the numerical simulations run using the Ansys Fluent software. For a qualitative analysis, the particles' paths through the inlet and bifurcations were observed whereas, for a quantitative analysis, the particle velocities were measured. Furthermore, oxygen transport was simulated and evaluated for different Reynolds numbers.

Results: In both qualitative and quantitative analyses, the results predicted by the numerical model and the ones outputted by the experimental model were in good agreement. These findings underscore the capability and potential of the developed numerical model. The examination of oxygen transport at various vertical positions within the organoid has revealed that for lower positions, oxygen transport predominantly occurs through diffusion, leading to a symmetric distribution of oxygen. Contrastingly, the convection phenomenon becomes more evident in the upper region of the organoid.

Conclusions: The successful validation of the numerical model against experimental data shows its accuracy and reliability in simulating the fluid flow within the OoC, which consequently can expedite the OoC design process by reducing the need for prototypes' fabrication and costly laboratory experiments.

Keywords: Biofluid mechanics; CFD; Computational simulations; Experimental validation; Microfluidics; Organ-on-a-chip.