Methods and apparatus for designing and measuring a cell-electrode impedance sensor to detect chemical and biological samples, including biological cells. The method of designing a cell-electrode impedance sensor comprises: determining a cell free cell-electrode impedance and a cell-covered cell-electrode impedance; obtaining a sensor sensitivity of the cell-electrode impedance measurement system; and choosing one or more design parameters of the cell-electrode impedance sensor to maximize the sensor sensitivity. When the frequency of AC signal between electrodes ranges from 10 kHz to 40 kHz, the sensitivity of the sensor is maximized.