A method of image-based analysis of multiple samples includes using a sample holder having multiple locations of interest and multiple focal structures that are each associated, one or more, with the multiple locations of interest, wherein the multiple samples are dispersed across the multiple locations of interest and obtaining image areas of the multiple locations of interest. Multiple digital image areas are thus obtained for use in an analysis of the multiple samples with each of the image areas including at least one of the locations of interest and at least one of the focal structures. An image processing algorithm is used to analyse each of the digital image areas and check if the focal structure indicates that the image area is in clear focus. An indication is provided and/or remedial action is taken if the image processing algorithm indicates that any digital image areas are out of focus.