A microfluidic gradient generator to simulate the oxygen microenvironment in cancer cell culture

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Journal Article
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Date
2018
Authors
Orcheston-Findlay L
Hashemi A
Garrill A
Nock VM
Abstract

Standard cancer lab models lack many attributes of the in-vivo cancer microenvironment. Oxygen levels for example are not commonly controlled in 2D cell-culture well plate experiments. However, low O2 (hypoxia) in particular is common in cancerous tissue due to high proliferation rates of cancer cells and inadequate vasculature. Hypoxia is also associated with cancer recurrence and drug resistance. We report a microfluidic system capable of exposing a 2D cell-culture to a dissolved oxygen gradient ranging from hypoxia (<5 mg/L) to hyperoxia (40 mg/L) for over 30 minutes, measurable in real-time using an integrated sensor film. The film incorporates a photostable, non-cytotoxic oxygen-sensitive fluorescent dye, which exhibits a linear response and high contrast (I0 /I100 = 12) within the range of interest, was integrated onto glass substrates as a cell culture substrate. To demonstrate the applicability of the platform, Ishikawa cancer cells were cultured on the platform and exposed to linear cross-stream oxygen gradients. The platform provides a valuable tool for the culture of cancer cells in an in-vivo like microenvironment and will enable more accurate screening of new anti-cancer drugs.

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Microfluidics, oxygen, cancer, fluorescent microscopy, gradient generator, thin film sensor
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ANZSRC fields of research
Field of Research::11 - Medical and Health Sciences::1112 - Oncology and Carcinogenesis::111201 - Cancer Cell Biology
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