Numerical Simulation of the Behavior of Toroidal and Spheroidal Multicellular Aggregates in Microfluidic Devices with Microwell and U-Shaped Barrier

Abstract

A microfluidic system provides an excellent platform for cellular studies. Most importantly, a three-dimensional (3D) cell culture model reconstructs more accurately the in vivo microenvironment of tissue. Accordingly, microfluidic 3D cell culture devices could be ideal candidates for in vitro cell culture platforms. In this paper, two types of 3D cellular aggregates, i.e., toroid and spheroid, are numerically studied. The studies are carried out for microfluidic systems containing U-shaped barrier as well as microwell structure. For the first time, we obtain oxygen and glucose concentration distributions inside a toroid aggregate as well as the shear stress on its surface and compare its performance with a spheroid aggregate of the same volume. In particular, we obtain the oxygen concentration distributions in three areas, namely, oxygen-permeable layer, multicellular aggregates and culture medium. Further, glucose concentration distributions in two regions of multicellular aggregates and culture medium are investigated. The results show that the levels of oxygen and glucose in the system containing U-shaped barriers are far more than those in the system containing microwells. Therefore, to achieve high levels of oxygen and nutrients, a system with U-shaped barriers is more suited than the conventional traps, but the choice between toroid and spheroid depends on their volume and orientation. The results indicate that higher oxygen and glucose concentrations can be achieved in spheroid with a small volume as well as in horizontal toroid with a large volume. The vertical toroid has the highest levels of oxygen and glucose concentration while the surface shear stress on its surface is also maximum. These findings can be used as guidelines for designing an optimum 3D microfluidic bioreactor based on the desired levels of oxygen, glucose and shear stress distributions.

Spheroids-on-a-chip: Recent advances and design considerations in microfluidic platforms for spheroid formation and culture

“…These structures are designed to help spheroid generation within a shorter period [122,123], with controllable and uniform diameters [124,125] and a compact spheroid shape [17,120]. Recently, we employed numerical simulations to find the necrotic core and hypoxic zone in a U-shape system containing spheroid [126] and compare the performance of such system in microfluidic platforms with either U-shaped barrier or microwell structure containing cell aggregates in toroidal shape [127].…”

Inventions and Innovations in Preclinical Platforms for Cancer Research

“…Spheroid diameter is confined to the microstructure size and the relative position of the microstructures is essential for efficient cell trapping. We have recently evaluated the oxygen and glucose distributions inside spheroids in such bioreactor [98] and compare the results with those inside toroidal multicellular aggregates [99].…”

Inventions and Innovations in Preclinical Platforms for Cancer Research

“…trapping. We have recently evaluated the oxygen and glucose distributions inside spheroids in such bioreactor [97] and compare the results with those inside toroidal multicellular aggregates [98].…”

“…The complicated geometries of the µSFCs and the limited diffusion of glucose and oxygen to spheroids create unpredictable concentration profiles within the cultured spheroids. Thus, mathematical and numerical analyses combined with experimental investigations are needed to predict the condition of hypoxia in the spheroids [107,[111][112][113][114][115][116]. The µSCC are designed for spheroid culture and their spheroid comes from an external source.…”