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In this paper, frequency response (dynamic compression and recovery) is suggested as a new physical marker to differentiate between breast cancer cells (MCF7) and normal cells (MCF10A). A single cell is placed on the laminated piezoelectric actuator and a piezoresistive microcantilever is placed on the upper surface of the cell at a specified preload displacement (or an equivalent force). The piezoelectric actuator excites the single cell in a sinusoidal fashion and its dynamic deformation is then evaluated from the displacement converted by measuring the voltage output through a piezoresistor in the microcantilever. The microcantilever has a flat contact surface with no sharp tip, making it possible to measure the overall properties of the cell rather than the local properties. These results indicate that the MCF7 cells are more deformable in quasi-static conditions compared with MCF10A cells, consistent with known characteristics. Under conditions of high frequency of over 50 Hz at a 1 [micro]m preload displacement, 1 Hz at a 2 [micro]m preload displacement, and all frequency ranges tested at a 3 [micro]m preload displacement, MCF7 cells showed smaller deformation than MCF10A cells. MCF7 cells have higher absorption than MCF10A cells such that MCF7 cells appear to have higher deformability according to increasing frequency. Moreover, larger preload and higher frequencies are shown to enhance the differences in cell deformability between the MCF7 cells and MCF10A cells, which can be used as a physical marker for differentiating between MCF10A cells and MCF7 cells, even for high-speed screening devices. [DOI: 10.1115/1.4002180] Keywords: breast cancer cell, physical markers, dynamic deformation, frequency response, piezoresistive microcantilever

Experimentally accessible tools to replicate the complex biological events of in vivo organs offer the potential to reveal mechanisms of disease and potential routes to therapy. In particular, models of inter-organ communication are emerging as the next essential step towards creating a body-on-a-chip, and may be particularly useful for poorly understood processes such as tumor immunity. In this paper, we report the first multi-compartment microfluidic chip that continuously recirculates a small volume of media through two ex vivo tissue samples to support inter-organ cross-talk via secreted factors. To test on-chip communication, protein release and capture were quantified using well-defined artificial tissue samples and model proteins. Proteins released by one sample were transferred to the downstream reservoir and detectable in the downstream sample. Next, the chip was applied to model the communication between a tumor and a lymph node, to test whether on-chip dual-organ culture could recreate key features of tumor-induced immune suppression. Slices of murine lymph node were co-cultured with tumor or healthy tissue on-chip with recirculating media, then tested for their ability to respond to T cell stimulation. Interestingly, lymph node slices co-cultured with tumor slices appeared more immunosuppressed than those co-cultured with healthy tissue, suggesting that the chip may successfully model some features of tumor-immune interaction. In conclusion, this new microfluidic system provides on-chip co-culture of pairs of tissue slices under continuous recirculating flow, and has the potential to model complex inter-organ communication ex vivo with full experimental accessibility of the tissues and their media. [ABSTRACT FROM AUTHOR]