A 3-D microfluidic combinatorial cell array.
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.
Department of Bioengineering, Division of Engineering and Applied Science, California Institute of Technology, 1200 E. California Blvd., MC 136-93, Pasadena, CA 91125, USA. mikeliu@mems.caltech.edu
Mike C
MC
Liu
Yu-Chong
YC
Tai
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D004129:Dimethylpolysiloxanes / Q000737:chemistry; D005898:Glass / Q000737:chemistry; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D008567:Membranes, Artificial; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D055616:Microtechnology / Q000379:methods*; D011108:Polymers / Q000737:chemistry; D051381:Rats; D018511:Systems Integration; D046888:Tissue Array Analysis / Q000295:instrumentation*; D014992:Xylenes / Q000737:chemistry
D000970:Antineoplastic Agents; D004129:Dimethylpolysiloxanes; D008567:Membranes, Artificial; D011108:Polymers; D014992:Xylenes; C011055:parylene; C013830:baysilon; D006861:Hydrogen Peroxide