Methods for detecting target analytes utilizing an array of wells are advantageous for detection of low concentrations of target analytes. Use of an array of wells requires sealing of the wells. The methods provided herein utilize digital microfluidics to seal wells of an array with a fluid that is immiscible with the aqueous liquid present in the wells to prevent evaporation and contamination of the aqueous fluid during analysis of signals from the wells. The disclosed method include generating a biphasic droplet composed of the immiscible fluid and an aqueous fluid. The immiscible fluid present in the biphasic droplet is moved over the array of wells to seal the wells by electrically actuating the aqueous fluid present in the biphasic droplet which in turn pulls the immiscible fluid.