Development of a fluidic platform for studying cancer cells under physiologically relevant oxygen conditions

Abstract

In solid cancer tumours the oxygen concentration can be lower than in the corresponding healthy tissue. This condition, known as hypoxia, impacts the behaviour and characteristics of the cancer cells and can result in tumour growth and resistance to treatment. Therefore, it is important to consider oxygen concentration when studying cancer cells in a research environment. Fluidics and organ-on-a-chip systems are popular and widely researched tools for representing organs and their microenvironments in vitro. This work presents development and fabrication of a novel system for studying cancer cells under a range of oxygen concentrations on the same fluidic chip.

The fabrication method developed in this project uses low-cost, biocompatible materials to rapidly prototype fluidic chips in a reproducible manner. An example chip is shown in Figure 1. Oxygen distribution in the channel network was investigated using computational simulations in COMSOL Multiphysics® 5.6 (Figure 2) and fluorescence microscopy experiments using Ru(BPY)3 (an oxygen sensitive fluorophore). Both methods confirmed the channel network supports a gradient across the chip based on two media inputs of different oxygen concentrations.

Operation and function of the platform was tested with liver carcinoma cell line HepG2/C3A. Cells were seeded throughout the channel network and responses to the different oxygen conditions were investigated via immunofluorescence staining. It was expected that cells in areas of the chip with lower oxygen concentration would show higher expression of the hypoxia inducible factor, HIF-1α, however, no significant differences in HIF-1α were observed. The results from the cell culture experiments indicate that further work is required to optimise the conditions for cancer cells.