A monolithic fabrication method of parallel-plate electrowetting-on-dielectric (EWOD) chips for digital microfluidics of picoliter droplets is disclosed. Instead of assembling a second substrate to form a top plate, the top plate is generated in situ as a thin-film membrane that forms a monolithic cavity having a gap height on the order of micrometers with excellent accuracy and uniformity. The membrane is embedded with EWOD driving electrodes and confines droplets against the device substrate to perform digital microfluidic operations. Two main attributes of the monolithic architecture that distinguish it from tradition methods are: (i) it enables excellent control of droplet dimensions down to the micrometer scale, and (ii) it does not require the typical alignment and assembly steps of the two plates.