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A 3-D microfluidic combinatorial cell array

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Abstract

We present the development of a three-dimensional (3-D) combinatorial cell culture array device featured with integrated three-input, eight-output combinatorial mixer and cell culture chambers. The device is designed for cell-based screening of multiple compounds simultaneously on a microfluidic platform. The final assembled device is composed of a porous membrane integrated in between a Parylene 3-D microfluidic chip and a PDMS microfluidic chip. The membrane turned the cell culture chambers into two-level configuration to facilitate cell loading and to maintain cells in a diffusion dominated space during device operation. Experimentally, we first characterized the combined compound concentration profile at each chamber using a fluorescence method. We then successfully demonstrated the functionality of the quantitative cell-based assay by culturing B35 rat neuronal cells on this device and screening the ability of three compounds (1,5-dihydroxyisoquinoline, deferoxamine, and 3-aminobenzoic acid) to attenuate cell death caused by cytotoxic hydrogen peroxide. In another experiment, we assayed for the combinatorial effects of three chemotherapeutic compound exposures (vinorelbine, paclitaxel, and γ-linolenic acid) on human breast cancer cells, MDA-MB-231. The same technology will enable the construction of inexpensive lab-on-a-chip devices with high-input combinatorial mixer for performing high-throughput cell-based assay and highly parallel and combinatorial chemical or biochemical reactions.

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Acknowledgements

This work was supported by NSF Center for Embedded Network Sensing (CCR-0120778). The authors would like to thank Trevor Roper and members of the Caltech Micromachining Laboratory for fabrication assistance.

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Authors and Affiliations

  1. Department of Bioengineering, Division of Engineering and Applied Science, California Institute of Technology, 1200 E. California Blvd., MC 136-93, Pasadena, CA, 91125, USA

    Mike C. Liu & Yu-Chong Tai

  2. Department of Electrical Engineering, Division of Engineering and Applied Science, California Institute of Technology, Pasadena, CA, 91125, USA

    Yu-Chong Tai

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  1. Mike C. Liu
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  2. Yu-Chong Tai
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Correspondence to Mike C. Liu.

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Liu, M.C., Tai, YC. A 3-D microfluidic combinatorial cell array. Biomed Microdevices 13, 191–201 (2011). https://doi.org/10.1007/s10544-010-9484-4

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