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Recent advances in mechanobiology have accumulated strong evidence showing close correlations between the physiological conditions and mechanical properties of cells. In this paper, a novel optomechanical technique to characterize the stiffness of single adherent cells attached on a substrate is reported. The oscillation in a cell's height on a vertically vibrating reflective substrate is measured with a laser Doppler vibrometer as apparent changes in the phase of the measured velocity. This apparent phase shift and the height oscillation are shown to be affected by the mechanical properties of human colorectal adenocarcinoma cells (HT-29). The reported optomechanical technique can provide high-throughput stiffness measurement of single adherent cells over time with minimal perturbation.

Biophysical studies on individual cells can help to establish the relationship between mechanics and biological function. In the case of cancer, mechanical properties of cells have been linked to metastatic activity and disease progression and can be crucial for understanding cellular physiology and metabolism. In this study, we report measurements of the stiffness of breast cancer cells using a novel silicon MEMS resonant sensor and validated the results with atomic force microscopy (AFM). We measured the mass and stiffness of individual benign (MCF-10A), non-invasive malignant (MCF-7), and highly-invasive malignant (MDA-MB-231) breast cancer cells using the silicon resonant MEMS sensors. The sensor extracts the average stiffness value of the whole cell and allows comparison of stiffness of different cell types. We found differences between the cell lines in both elasticity and viscosity, and confirmed our observations through independent measurements with atomic force microscopy (AFM). Coupled with measurements over time, this approach could lead to a multimodal investigation of both growth and physical properties of single cells. The mechanical property sensitivity and resolution of these pedestal sensors were investigated to understand the significance of the frequency shift during operation. The lowest achievable spring constant and damping constant resolutions have a range of 0.06 to 17.10 mN m(-1) and 1.63 to 1.96 nN s m(-1), respectively, measured across the range of physiological cell mechanical properties.

MEMS resonant mass sensors can measure the mass of individual cells, though long-term growth measurements are limited by the movement of cells off the sensor area. Micro-patterning techniques are a powerful approach to control the placement of individual cells in an arrayed format. In this work we present a method for micro-patterning cells on fully suspended resonant sensors through select functionalization and passivation of the chip surface. This method combines high-resolution photolithography with a blanket transfer technique for applying photoresist to avoid damaging the sensors. Cells are constrained to the patterned collagen area on the sensor by pluronic acting as a cell adhesion blocker. This micro-patterning method enables long-term growth measurements, which is demonstrated by a measurement of the change in mass of a human breast cancer cell over 18 h.