Digital microfluidic (DMF) methods and apparatuses (including devices, systems, cartridges, DMF readers, etc.), and in particular DMF apparatuses and methods adapted for large volume. For example, described herein are methods and apparatuses for DMF using an air gap having a width of the gap that may be between 0.3 mm and 3 mm. Also described herein are DMF readers for use with a DMF cartridges, including those adapted for use with large air gap/large volume, although smaller volumes may be used as well.