The present invention, in one aspect, provides systems and methods for using a single slug or multiple slugs containing one or more calibrators to determine a relationship between temperature and an electrical characteristic of the thermal sensor for use in connection with calibrating thermal sensors. In some embodiments, the present invention uses the described calibrator systems and methods to calibrate thermal control elements on a microfluidic device. In non-limiting embodiment, the calibrator can be one or more of droplets, plugs, slugs, segments or a continuous flow of any appropriate solution that, when heated, yields a thermal response profile with a plurality of features (e.g., maxima, minima, inflection points, linear regions, etc.).