Journal
ANALYTICAL CHEMISTRY
Volume 90, Issue 20, Pages 11899-11907Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.analchem.8b02070
Keywords
-
Categories
Funding
- National Natural Science Foundation of China [81872835, 21621003]
- Ministry of Science and Technology of the People's Republic of China [2017YFC0906902, 2017ZX09301032, 2013ZX09507005]
Ask authors/readers for more resources
Oxygen deprivation is a common feature in a variety Pyrogallo of cancer tissues and associated with tumor progression, acquisition of antiapoptotic potential, and clinical therapeutic resistance. Thus, great interest has been aroused to develop new platforms or approaches of activity assays to impact on the hypoxic micro environment and oxygen-dependent drug responses to improve the productivity of new drug discovery. In this study, an integrated microsystem is established to combine the cytotoxic and genotoxic tests together for continuous multiple measurements under mimicking hypoxic tumor microenvironment. We fabricated a double-layer chip device by combining a single-cell-arrayed agarose layer with a microfluidics-based oxygen gradient-generating layer using a PDMS membrane. Using tirapazamine (TPZ) and blemycin (BLM) as model anticancer drugs, we demonstrated its application and performance in single cell loading, cell cultivation, and subsequent drug treatment as well as in situ analysis of oxygen-dependent cytotoxicity and genotoxicity of anticancer drugs. The results demonstrated the opposite oxygen-dependent toxicity of TPZ and BLM, which also indicated that the formation of DNA breaks is related with cell apoptosis. Compared with the traditional assays, this device takes advantage of microfluidic phenomena to generate various oxygen concentrations while exhibiting the combinatorial diversities achieved by the single cell microarray, offering a powerful tool to study single cell behaviors and responses under different oxygen conditions with desired high-content and high-throughput capabilities.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available