A slide holder assembly and method for use in high content screening of a comet assay. The slide holder assembly has an inside surface and is configured to receive a slide holding a plurality of biological cells on a top surface thereof. When the slide is secured within the slide holder assembly, the inside surface of the slide holder assembly and the top surface of the slide combine to form a cavity having an open top end. The cavity is watertight and configured to hold a liquid therein. A method of performing a comet assay using a slide disposed within a slide holder assembly. The method includes performing encapsulation, lysis, electrophoresis, staining, and imaging of cells on the slide while the slide remains secured within the slide holder assembly.