A microfluidic control system for controlling an EWOD device has an enhanced thermal control system for generating a temperature profile within an EWOD device that is inserted into the microfluidic control system. The microfluidic control system includes a housing that defines an aperture for receiving an EWOD device; an active heating component located within the housing at a base of the aperture; and a lid attached to the housing that is moveable between a closed position and an open position, the lid including a thermal control component. When the lid is in the closed position, the thermal control component is positioned at the aperture and aligned oppositely from the active heating component. The active heating component may include a plurality of independently controllable individual heating elements, and the thermal control component may include a respective plurality of individual thermal control elements. The microfluidic control system further may include a clamp positioned between the lid and the housing for retaining the EWOD device.