In this research, the development of a highly sensitive FET based biosensor technology for whole cell sensing and cellular transmembrane potential measurement is discussed and a quantitative model is proposed to elucidate the sensor mechanism. Electrical double layer (EDL) gated FET biosensor platform offers high sensitivity target analyte detection, even in high ionic strength solutions, thereby eliminating the need for complex sample pre-processing methods. Using this sensor platform, we have developed a whole cell sensing technology that can detect and count cells, and monitor cellular bioelectric signals such as transmembrane potential changes. A quantitative model is developed to explain the sensor mechanism and theoretical prediction shows good agreement with experimental results. The changes in the cellular transmembrane potential upon extracellular stimulus is modeled based on the EDL FET sensor response. Our investigation reveals that EDL FET biosensor platform can be used to study the bioelectric signals of cells, dynamically which is highly relevant to cell biology in applications of drug development, ion channel studies and disease model establishment. This sensor technology can also be used for point of care diagnostics, in the diagnosis and prognosis of diseases such as cancer. Since the discovery of cells, the basic building blocks of life, they have remained as crucial links to unraveling the pathophysiology of disease and understanding the complex, fundamental processes that sustain life. Several technologies are employed for the identification and the study of fundamental cell biology. Optical technologies are commonly used for most types of cell based experiments. Flow cytometry is the traditional choice where cells are flown in through a channel and optical microscopy is used to image, analyze and characterize cells.1,2 Often fluorescent probes are used to image specific molecules within the cell to either identify the type of cell or track particular cellular functions.3,4 Newer technologies such as surface plasmon resonance (SPR) and resonant waveguide grating (RWG) have been well established for cellular investigation.5-7 However, these technologies require sophisticated instrument and trained laboratory staff to perform the experiments, which significantly increases the associated cost and inconvenience. Also, long turnaround times, photobleaching of fluorescent probes and poor signal to noise ratio are some of the issues that need to be addressed to improve the efficiency and reliability of the optical technologies.Recently, several micro/nano technology based cellular diagnostic and analytical platforms have been developed to overcome the limitations of traditional optical based technologies. [8][9][10][11] Among them, electronic micro/nano sensors are particularly attractive owing to their high sensitivity response, miniaturized design, cost-effectiveness and speedy response. Field effect transistors (FETs) are surface affinity type sensors that can amplify the biological interactions ...