Platform for High-Throughput Testing of the Effect of Soluble Compounds on 3D Cell Cultures

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Platform for High-Throughput Testing of the Effect of Soluble Compounds on 3D Cell Cultures

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Title: Platform for High-Throughput Testing of the Effect of Soluble Compounds on 3D Cell Cultures
Author: Deiss, Frédérique; Mazzeo, Aaron; Hong, Estrella; Ingber, Donald Elliott; Derda, Ratmir; Whitesides, George McClelland

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Citation: Deiss, Frédérique, Aaron Mazzeo, Estrella Hong, Donald E. Ingber, Ratmir Derda, and George M. Whitesides. 2013. “Platform for High-Throughput Testing of the Effect of Soluble Compounds on 3D Cell Cultures.” Analytical Chemistry 85(17): 8085–8094.
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Abstract: In vitro 3D culture could provide an important model of tissues in vivo, but assessing the effects of chemical compounds on cells in specific regions of 3D culture requires physical isolation of cells and thus currently relies mostly on delicate and low-throughput methods. This paper describes a technique (“cells-in-gels-in-paper”, CiGiP) that permits rapid assembly of arrays of 3D cell cultures and convenient isolation of cells from specific regions of these cultures. The 3D cultures were generated by stacking sheets of 200-μm-thick paper, each sheet supporting 96 individual “spots” (thin circular slabs) of hydrogels containing cells, separated by hydrophobic material (wax, PDMS) impermeable to aqueous solutions, and hydrophilic and most hydrophobic solutes. A custom-made 96-well holder isolated the cell-containing zones from each other. Each well contained media to which a different compound could be added. After culture and disassembly of the holder, peeling the layers apart “sectioned” the individual 3D cultures into 200-μm-thick sections which were easy to analyze using 2D imaging (e.g., with a commercial gel scanner). This 96-well holder brings new utilities to high-throughput, cell-based screening, by combining the simplicity of CiGiP with the convenience of a microtiter plate. This work demonstrated the potential of this type of assays by examining the cytotoxic effects of phenylarsine oxide (PAO) and cyclophosphamide (CPA) on human breast cancer cells positioned at different separations from culture media in 3D cultures.
Published Version: doi:10.1021/ac400161j
Terms of Use: This article is made available under the terms and conditions applicable to Open Access Policy Articles, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#OAP
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:12361276
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