Methods for correcting for thermal drift in microscopy images

Methods for correcting for thermal drift in microscopy images are described. One such method includes receiving an original image for correction, the original image having been generated using microscopy, receiving information indicative of a feature selected from within the original image by a user, the selected feature including an edge, storing the original image in a database including a plurality of images, each having one or more features, correlating the selected feature with one of the one or more features stored in the database to identify a first plurality of points defining the edge, removing one or more points of the first plurality of points using an outlier rejection technique, generating a smoothing spline approximation for a second plurality of points defining the edge, and generating a corrected image by shifting points of the original image in accordance with the smoothing spline approximation.