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Integrated microfluidic devices for combinatorial cell-based assays

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Abstract

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.

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Acknowledgements

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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Authors and Affiliations

  1. Department of Mechanical and Aerospace Engineering, University of California, Los Angeles, CA, 90095, USA

    Zeta Tak For Yu

  2. Crump Institute for Molecular Imaging, University of California, Los Angeles, CA, 90095, USA

    Zeta Tak For Yu, Ken-ichiro Kamei, Hiroko Takahashi, Xiaopu Wang, George Wenfu He, Caius G. Radu & Hsian-Rong Tseng

  3. Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA

    Zeta Tak For Yu, Ken-ichiro Kamei, Xiaopu Wang, George Wenfu He, Robert Silverman, Caius G. Radu, Owen N. Witte & Hsian-Rong Tseng

  4. Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA, 90095, USA

    Chengyi Jenny Shu & Owen N. Witte

  5. The Howard Hughes Medical Institute, University of California, Los Angeles, CA, 90095, USA

    Owen N. Witte

  6. Department of Chemistry and Chemical Biology, Institute for Advanced Materials, Devices and Nanotechnology, The Rutgers Stem Cell Research Center, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA

    Ki-Bum Lee

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  1. Zeta Tak For Yu
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  8. Caius G. Radu
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  10. Ki-Bum Lee
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  11. Hsian-Rong Tseng
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Correspondence to Caius G. Radu, Owen N. Witte, Ki-Bum Lee or Hsian-Rong Tseng.

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Zeta Tak For Yu and Ken-ichiro Kamei contributed equally to this work.

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Yu, Z.T.F., Kamei, Ki., Takahashi, H. et al. Integrated microfluidic devices for combinatorial cell-based assays. Biomed Microdevices 11, 547–555 (2009). https://doi.org/10.1007/s10544-008-9260-x

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