A1: Micro / Nano Biomedical Devices & System

MICROFLUIDIC DEVICE FOR INVESTIGATION OF CELLULAR RESPONSES TO HETEROGENEITY OF OXYGEN TENSION


Kenichi Funamoto1, Roger Kamm2
 

1Tohoku University, Japan; 2Massachusetts Institute of Technology, USA


In the tumor microenvironment, cells are exposed to spatial and temporal heterogeneity of oxygen tension. Hyperproliferation of cells causes a chronic hypoxic condition with a nonuiform spatial distribution of oxygen tension. In addition, immature vascularization in the tumor causes a temporal variation of oxygen tension due to ischemia and reperfusion. Hence, it is important to understand cellular responses and cellcell interactions under temporal and spatial variations of oxygen tension. The authors previously developed a microfluidic device for observation of cell behaviors in a three-dimensional space under controlled oxygen tension. Oxygen tension inside the device was controlled by supplying gas mixture at a predefined oxygen concentration to the gas channels flanking the media and gel channels (cell culture channels). Although a uniform oxygen tension or an oxygen gradient were established, the lowest oxygen level was ~3% and it took more than one hour to establish a steady-state. In this study, the microfluidic device was modified to overcome those limitations in controllability of oxygen tension. Gas channels were repositioned to be above the media channels to enhance gas exchange between the gas channels and cell culture channels. Numerical simulations revealed changes of oxygen tension in the microfluidic device as a function of the system parameters such as device thickness, size, the media and gas flow rates. Then, oxygen tensions created with the appropriate settings were validated by using oxygen-sensing chemical complex on a bottom glass cover slip. The computational and experimental results showed more rapid change and lower level of oxygen tension than in the previous device. Usability of the developed device for cellular experiments was examined by observing the migrations of breast cancer cells under controlled oxygen tensions. When oxygen condition was switched between normoxia and hypoxia, an oxygen-dependent change of motility of the cancer cells was observed

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