Integrated microfluidic devices for combinatorial cell-based assays
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The development of miniaturized cell culture platforms for performing parallel cultures and combinatorial assays is important in cell biology from the single-cell level to the system level. In this paper we developed an integrated microfluidic cell-culture platform, Cell-microChip (Cell-μChip), for parallel analyses of the effects of microenvironmental cues (i.e., culture scaffolds) on different mammalian cells and their cellular responses to external stimuli. As a model study, we demonstrated the ability of culturing and assaying several mammalian cells, such as NIH 3T3 fibroblast, B16 melanoma and HeLa cell lines, in a parallel way. For functional assays, first we tested drug-induced apoptotic responses from different cell lines. As a second functional assay, we performed “on-chip” transfection of a reporter gene encoding an enhanced green fluorescent protein (EGFP) followed by live-cell imaging of transcriptional activation of cyclooxygenase 2 (Cox-2) expression. Collectively, our Cell-μChip approach demonstrated the capability to carry out parallel operations and the potential to further integrate advanced functions and applications in the broader space of combinatorial chemistry and biology.
KeywordsMicrofluidic devices Cell-based assay Apoptosis Transfection Cell culture
This research was supported by the NIH NanoSystems Biology Cancer Center, the DOE-UCLA Institute of Molecular Medicine and the NIH-UCLA Center for In Vivo Imaging in Cancer Biology and Siemens Medical Solutions USA Inc. We thank Stephanie M. Shelly, Dan Rohle, Shirley Quan and Mireille Riedinger for the outstanding technical support with conventional cell culture conditions. ONW is an Investigator of the Howard Hughes Medical Institute. CGR was supported by a Developmental Project Award (ICMIC, NIH/NCI grant no. CA08630). C.J.S. was supported by a National Institutes of Health (NIH) Research Training in Pharmacological Sciences training grant PHS T32 CM008652.
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