A Proof-of-Concept Study Using Numerical Simulations of an Acoustic Spheroid-on-a-Chip Platform for Improving 3D Cell Culture

Microfluidic lab-on-chip devices are widely being developed for chemical and biological studies. One of the most commonly used types of these chips is perfusion microwells for culturing multicellular spheroids. The main challenge in such systems is the formation of substantial necrotic and quiescent zones within the cultured spheroids. Herein, we propose a novel acoustofluidic integrated platform to tackle this bottleneck problem. It will be shown numerically that such an approach is a potential candidate to be implemented to enhance cell viability and shrinks necrotic and quiescent zones without the need to increase the flow rate, leading to a significant reduction in costly reagents' consumption in conventional spheroid-on-a-chip platforms. Proof-of-concept, designing procedures and numerical simulation are discussed in detail. Additionally, the effects of acoustic and hydrodynamic parameters on the cultured cells are investigated. The results show that by increasing acoustic boundary displacement amplitude (d(0)), the spheroid's proliferating zone enlarges greatly. Moreover, it is shown that by implementing d(0) = 0.5 nm, the required flow rate to maintain the necrotic zone below 13% will be decreased 12 times compared to non-acoustic chips.

Automated summary

Microfluidic lab-on-chip devices are widely used for chemical and biological studies, with perfusion microwells for culturing multicellular spheroids being a common type. A novel acoustofluidic integrated platform is proposed to enhance cell viability and reduce necrotic and quiescent zones in cultured spheroids without increasing flow rate, thus decreasing reagent consumption significantly. Numerical simulations show that increasing acoustic boundary displacement amplitude enlarges the proliferating zone of spheroids, and implementing certain parameters can greatly reduce the required flow rate to maintain necrotic zones.