A microfluidic device for noninvasive cell electrical stimulation and extracellular field potential analysis.

We developed a device that can quickly apply versatile electrical stimulation (ES) signals to cells suspended in microfluidic channels and measure extracellular field potential simultaneously. The device could trap cells onto the surface of measurement electrodes for ES and push them to the downstream channel after ES by increasing pressure for continuous measurement. Cardiomyocytes, major functional cells in heart, together with human fibroblast cells and human umbilical vein endothelial cells, were tested with the device. Extracellular field potential signals generated from the cells were recorded. We found that under electrical stimulation, cardiomyocytes were triggered to alter their field potential, while non-excitable cells were not triggered. Hence this device can noninvasively distinguish electrically excitable cells from electrically non-excitable cells. Results have also shown that increased cardiomyocyte cell number led to increased magnitude and occurrence of the cell responses. This relationship could be used to detect the viable cells in a cardiac tissue. Application of variable ES signals on different cardiomyocyte clusters has shown that the application of ES clearly boosted cardiomyocytes electrical activities according to the stimulation frequency. In addition, we confirmed that the device can apply ES onto and detect the electrical responses from a mixed cell cluster; the responses from the mixed cluster is dependent on the ratio of cardiomyocytes. These results demonstrated that our device could be used as a tool to optimize ES conditions to facilitate the functional engineered cardiac tissue development.