Abstract
Microfluidic devices have been widely used for biological and cellular studies. Microbioreactors for three-dimensional (3D) multicellular spheroid culture are now considered as the next generation in in vitro diagnostic tools. The feasibility of using 3D cell aggregates to form multicellular spheroids in a microbioreactor with U-shaped barriers has been demonstrated experimentally. A barrier array is an alternative to commonly used microwell traps. The present study investigates oxygen and glucose concentration distributions as key parameters in a U-shaped array microbioreactor using finite element simulation. The effect of spheroid diameter, inlet concentration and flow rate of the medium are systematically studied. In all cases, the channel walls are considered to be permeable to oxygen. Necrotic and hypoxic or quiescent regions corresponding to both oxygen and glucose concentration distributions are identified for various conditions. The results show that the entire quiescent and necrotic regions become larger with increasing spheroid diameter and decreasing inlet and wall concentration. The shear stress (0.5–9 mPa) imposed on the spheroid surface by the fluid flow was compared with the critical values to predict possible damage to the cells. Finally, optimum range of medium inlet concentration (0.13–0.2 mM for oxygen and 3–11 mM for glucose) and flow rate (5–20 μL/min) are found to form the largest possible multicellular spheroid (500 μm), without any quiescent and necrotic regions with an acceptable shear stress. The effect of cell-trap types on the oxygen and glucose concentration inside the spheroid was also investigated. The levels of oxygen and glucose concentration for the microwell are much lower than those for the other two traps. The U-shaped barrier created with microposts allows for a continuous flow of culture medium, and so improves the glucose concentration compared to that in the integrated U-shaped barrier. Oxygen concentration for both types of U-shaped barriers is nearly the same. Due to the advantage of using U-shaped barriers to culture multicellular spheroids, the results of this paper can help to choose the experimental and design parameters of the microbioreactor.
Highlights
Microfluidic systems have been used as practical and powerful tools for cell studies and can replace conventional in vitro systems and even animal models [1,2]
This paper aims to numerically investigate oxygen and glucose concentration distributions in multicellular spheroid entrapped in a three-dimensional microfluidic device with an oxygen-permeable wall, an integrated U-shaped barrier or a U-shaped barrier created with microposts or microwell
Spheroid diameter is a critical parameter for examining the possibility of hypoxia or necrosis
Summary
Microfluidic systems have been used as practical and powerful tools for cell studies and can replace conventional in vitro systems and even animal models [1,2]. Mechanical trapping has been widely used for tumor spheroid generation [14] This method utilizes barriers such as micropillars or microwells located in the channel to trap the cells and to create multicellular aggregates. The present study numerically investigates a microfluidic system with an integrated U-shaped barrier similar to that used in references [14,15,16] and compares its performance with barriers formed by microposts and microwell structure
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
