A surface acoustic wave (SAW) microfluidic chip was designed to measure the compressibility of cells and to differentiate cell mechanophenotypes. Polystyrene microbeads and poly(methylmethacrylate) (PMMA) microbeads were first tested in order to calibrate and validate the acoustic field. We observed the prefocused microbeads being pushed into the new pressure node upon phase shift. The captured trajectory matched well with the equation describing acoustic radiation force. The compressibility of polystyrene microbeads and that of PMMA microbeads was calculated, respectively, by fitting the trajectory from the experiment and that simulated by the equation across a range of compressibility values. Following, A549 human alveolar basal epithelial cells (A549 cells), human airway smooth muscle (HASM) cells, and MCF-7 breast cancer cells were tested using the same procedure. The compressibility of each cell from the three cell types was measured also by fitting trajectories between the experiment and that from the equation; the size was measured by image analysis. A549 cells were more compressible than HASM and MCF-7 cells; HASM cells could be further distinguished from MCF-7 cells by cell size. In addition, MCF-7 cells were treated by colchicine and 2-methoxyestradiol to disrupt the cell microtubules and were found to be more compressible. Computer simulation was also carried out to investigate the effect of cell compressibility and cell size due to acoustic radiation force to examine the sensitivity of the measurement. The SAW microfluidic method is capable of differentiating cell types or cells under different conditions based on the cell compressibility and the cell size.

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