A study of mechanical cues of cells with a piezoelectric transducer array---a mechanical approach for cellular diagnostics

In recent years, mechanical properties of unhealthy cells had been recognized as a potential biomarker for disease diagnostics. For example, cancer cells can be five times more compliant than normal cells and exert almost twice the surface tractions on adhered substrate. Malaria-infected red blood cells, on the other hand, become more stiff and sticky, and they cannot readily suspend in blood samples. However, due to the complexities of the available methods in cell mechanics, researchers cannot perform massive screening of different cell samples and verify the reliability of this biomarker. To overcome this obstacle and to the goal of performing rapid disease diagnosis with multiple cell samples, a microfluidic platform integrated with a piezoelectric transducer array is developed. This platform aims at sensing the variations in surface tractions originated from cells anchored on the transducer surface as a means to differentiate healthy vs. unhealthy cells.;The thin-film piezoelectric transducer serves as a real-time and less invasive sensor that monitors tractions exerted by a cell or several cells anchored on its surface. Extensive theoretical analyses and finite-element simulations were conducted, which showed that cell tractions directly modulated the pre-designed resonant behaviors of the piezoelectric transducer. These results demonstrated, for the first time, that the application and changes in these surface tractions resulted in resonant and anti-resonant frequency shifts in the impedance response of the transducer. The rapid turn around time is achieved by integrating a perfusion-based microbioreactor, which shortens the path and time for cell to anchor on transducer surfaces. In addition, by using the gap between suspended transducers as the high-aspect-ratio barriers, a high flow resistance in the culture chamber is created to minimize shear stress on the transducer surfaces. Experimental results showed that the fluid transport mechanisms in the culture chamber were dominated by diffusion, and the shear stress was successfully suppressed below milli-pascal range on the transducer surfaces. This design offers minimal confounding factors in the mechanical force detections on cells cultured on the surface of transducers. The success of this research will potentially lead to the use of cell tractions as biomarkers for practical clinical diagnostics.