Microfluidic systems for cell-based screening of cancer treatments under controlled hypoxia
Tumour hypoxia (low oxygen levels) can impact the effectiveness of cancer treatments. Abnormal blood vessels in tumours can lead to oxygen gradients and chronic and transient (intermittent) hypoxic regions, with hypoxia/reperfusion rates of a few cycles per hour. Transient hypoxia can promote tumour aggressiveness and changes in cell phenotype compared with chronic hypoxia. Including these effects in early in vitro screening stages could yield results more predictive during subsequent in vivo tests. Since state-of-the-art in vitro platforms such as well plates, glass dishes, hypoxia chambers, and even custom stirred hypoxic vessels can’t easily reproduce these effects due to long equilibration times (hours), we use microfluidic devices which offer the potential to control and reproduce more realistic environments due to their smaller size scales.
Video showing time-varying fluidic oxygen levels within a microfluidic device. Left: Gaseous oxygen levels supplied to the microfluidic device (red), and average oxygen levels at the bottom of the water-filled cell culture channel (black), measured (using fluorescence microscopy) by the integrated ratiometric optical oxygen sensor films. Fluidic oxygen levels closely follow gaseous oxygen supply, with a fast switching time of less than 10 minutes. Right: False-colour oxygen levels (ranging from 0% (blue) to 10% (red)) measured by the integrated sensor films, overlaid upon a brightfield image of the microfluidic device with trapping structures for 3-D cultures. After equilibration, the oxygen levels are uniform across the width and length of the channel. For more information please see Sensors 2015, 15(8), 20030-20052; doi:10.3390/s150820030.
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