Abstract
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 (), the spheroid’s proliferating zone enlarges greatly. Moreover, it is shown that by implementing = 0.5 nm, the required flow rate to maintain the necrotic zone below 13% will be decreased 12 times compared to non-acoustic chips.
Highlights
Cancer is the second leading cause of death globally, accounting for more than 8 million deaths per year [1]
Based on the results provided in this work, oxygen is the critical element in the necrotic zone formation since it is depleted faster than glucose
These results show that oxygen and glucose can both be the cause of 18 acoustics of necrosis and the formation of the quiescent zone, and the integration of to the system improves the conditions for both factors
Summary
Cancer is the second leading cause of death globally, accounting for more than 8 million deaths per year [1]. Barisam et al numerically studied the necrotic cores and quiescent zones in spheroids cultured in U-shaped barrier microfluidic chips and investigated the effect of several hydrodynamic parameters on multicellular aggregates in such platforms [26]. Increasing the flow rate is another possible solution to prevent necrotic cores of in vitro spheroid culture platforms While this approach improves the nutrition distribution inside the spheroid, it suffers from serious downsides: (1) Higher flow rates require more culture media and drugs in long-term culturing and drug screening. To address the aforementioned challenges in spheroid-on-chip microsystems, in this study we took a step forward towards integrating acoustic microfluidics with conventional spheroid-on-chip platforms as a novel technique to decrease consumption of the reagents and decrease the associated shear stress on the cultured cells. A comparison between on-chip spheroid culturing with and without acoustofluidic integration is carried out to better illustrate the benefits of integrating acoustic fields into spheroid-on-chip systems
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