Drug Dose Responses Of 3d Cancer Spheroids In Microfluidics

FASEB JOURNAL(2015)

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Abstract
A major drawback in the development of new cancer therapeutics is the use of two‐dimensional (2D) monolayer cultures as models for solid tumours. A solution lies in the use of three‐dimensional (3D) multicellular aggregate models, known as spheroids or organoids. These mimic the interactions between cells within a tumour, the morphology and the microenvironment of tumours, representing a simplified but more physiologically relevant in vitro system for drug screening than that provided by 2D bioassays. In this study, we developed a novel microfluidic platform that allows the formation and long‐term culture of hundreds of multicellular cancer spheroids, retaining complete control over the number and the size of spheroids grown, the ability to deliver chemical compounds in a customisable concentration gradient format and the ability to recover the spheroids for off‐chip post‐processing after treatment. UVW cells, a human brain high‐grade glioma cell line, were used to create spheroids in an array format and were exposed to a microfluidic concentration gradient of cisplatin. Results showed that the growth of 3D glioma spheroids after treatment is reduced in a concentration‐dependent manner and that a dose response curve can be obtained from a single device. These findings demonstrate the suitability of the system for high‐throughput drug screening, combination therapeutics and the potential for use with biopsy samples.
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Key words
3d cancer spheroids,microfluidics
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