We present the development of a three-dimensional (3-D), on-glass combinatorial cell culture array chip featured with integrated three-input, eight-output combinatorial mixers and cell culture chambers. The device is designed to simultaneously screen for the effects of multiple compounds and concentrations on cultured cells. Experimentally, we first developed a precise way to characterize the combined compound concentration profile at each chamber with a fluorescence method. We then successfully demonstrated the functionality of the cell assay by culturing neuron cells on this device and screening the ability of three chemicals to attenuate cell death caused by cytotoxic hydrogen peroxide. Based on the same technology, the number of inputs and outputs of the combinatorial mixer can be scaled-up to construct labon-chip devices for performing high-throughput cell-based assay and highly parallel and combinatorial chemical or biochemical reactions with reduced labors, reagents, and time.
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